[ { "record_id": "GLY_000594_1_0", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9701192", "r hsa", "hsa 9701192", "r hsa 9701192" ] }, { "record_id": "GLY_000594_1_0", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective homologous", "homologous recombination", "recombination repair", "due to", "to brca1", "brca1 loss", "loss of", "of function", "defective homologous recombination", "homologous recombination repair", "repair hrr", "hrr due", "due to brca1", "to brca1 loss", "brca1 loss of", "loss of function", "defective homologous recombination repair", "recombination repair hrr", "hrr due to", "due to brca1 loss", "to brca1 loss of", "brca1 loss of function", "homologous recombination repair hrr", "repair hrr due", "hrr due to brca1", "due to brca1 loss of", "to brca1 loss of function", "in addition", "addition to", "to its", "its role", "role in", "in dna", "dna double", "double strand", "strand break", "brca1 plays", "plays an", "an important", "important role", "in homologous", "of dsbs", "dsbs by", "by directly", "directly promoting", "promoting recruitment", "recruitment of", "of palb2", "palb2 and", "and indirectly", "indirectly brca2", "brca2 to", "to dsb", "dsb repair", "repair sites.", "sites. in", "brca1 increases", "increases the", "the speed", "speed and", "and processivity", "processivity of", "of dna", "dna end", "end resection", "resection which", "which consists", "consists of", "of 5\u2032\u20133\u2032", "5\u2032\u20133\u2032 nucleolytic", "nucleolytic degradation", "degradation of", "cruz garcia", "garcia et", "et al.", "al. 2014", "2014 .", ". the", "the direct", "direct brca1", "brca1 interaction", "interaction with", "with palb2", "palb2 helps", "helps to", "to fine", "fine tune", "tune the", "the localization", "localization of", "of brca2", "brca2 and", "and rad51", "rad51 at", "at dsbs", "zhang et", "al. 2009", "sy et", "2009 .", ". palb2", "palb2 simultaneously", "simultaneously interacts", "interacts with", "with rad51", "and rad51ap1", "modesti et", "al. 2007", "wiese et", "buisson et", "al. 2010", "dray et", "2010 .", "rad51ap1 synergistically", "synergistically stimulate", "stimulate rad51", "rad51 recombinase", "recombinase activity", "thus enhancing", "enhancing rad51", "rad51 mediated", "mediated strand", "strand exchange", "branch migration", "and promoting", "promoting the", "the formation", "formation of", "of d", "d loop", "loop structures", "synaptic complex", "complex assembly", "assembly .", ". a", "a d", "loop structure", "structure is", "is formed", "formed when", "when complementary", "complementary duplex", "duplex dna", "sister chromatid", "chromatid arm", "is progressively", "progressively invaded", "invaded by", "by the", "the rad51", "rad51 nucleoprotein", "nucleoprotein filament", "with base", "base pairing", "pairing of", "of the", "the invading", "invading ssdna", "ssdna and", "and the", "the complementary", "complementary sister", "chromatid dna", "dna strand", "sung et", "al. 2003", "2003 .

the", ".

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the", "function\\.

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the", "2003 .

the n", ".

the n terminal", "n terminal region", "terminal region of", "region of brca1", "of brca1 contains", "brca1 contains the", "contains the ring", "the ring domain", "domain residues", "residues 7 98", "required for the", "for the heterodimerization", "the heterodimerization of", "heterodimerization of brca1", "of brca1 with", "brca1 with bard1.", "with bard1. brca1:bard1", "bard1. brca1:bard1 heterodimer", "brca1:bard1 heterodimer has", "heterodimer has e3", "has e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase activity", "ligase activity which", "activity which is", "which is important", "is important for", "important for dna", "for dna repair", "repair drost", "drost et al.", "et al. 2011", "al. 2011 .", "2011 . several", ". several missense", "several missense mutations", "missense mutations within", "mutations within the", "within the ring", "ring domain have", "domain have been", "have been linked", "been linked to", "linked to increased", "to increased risks", "increased risks of", "risks of developing", "of developing breast/ovarian", "developing breast/ovarian cancers", "cancers bouwman", "bouwman et al.", "et al. 2013", "2013 starita", "starita et al.", "et al. 2018", "al. 2018 .", "2018 . brca1", ". brca1 mutant", "brca1 mutant proteins", "mutant proteins impaired", "proteins impaired in", "impaired in bard1", "in bard1 binding", "bard1 binding are", "binding are annotated", "are annotated in", "annotated in the", "in the pathway", "the pathway \\defective", "pathway \\defective dna", "\\defective dna double", "strand break response", "break response due", "response due to", "loss of function\\.

the", "of function\\.

the c", "function\\.

the c terminal", "c terminal region", "of brca1 which", "brca1 which contains", "which contains two", "contains two coiled", "two coiled coil", "coiled coil domains", "domains residues", "residues 1397 1424", "1424 and", "and two brct", "two brct domains", "residues 1642 1736", "1642 1736 for", "1736 for brct", "for brct 1", "1 residues", "residues 1756 1855", "1756 1855 for", "1855 for brct", "for brct 2", "2 is", "is involved in", "involved in palb2", "in palb2 binding", "binding with", "with the second", "the second coiled", "second coiled coil", "coiled coil domain", "coil domain being", "domain being essential", "essential sy", "2009 . several", ". several cancer", "several cancer associated", "cancer associated brca1", "associated brca1 missense", "brca1 missense mutants", "missense mutants that", "mutants that affect", "that affect the", "affect the c", "the c terminal", "terminal region were", "region were shown", "were shown to", "shown to have", "to have reduced", "have reduced ability", "reduced ability to", "ability to bind", "to bind palb2", "palb2 sy", "2009 . in", ". in addition", "addition many", "many nonsense and", "nonsense and frameshift", "and frameshift mutations", "frameshift mutations in", "mutations in brca1", "in brca1 reported", "brca1 reported in", "reported in cancer", "in cancer result", "cancer result in", "result in truncated", "in truncated proteins", "truncated proteins that", "proteins that lack", "that lack the", "lack the palb2", "the palb2 binding", "palb2 binding domain.", "in addition to its", "addition to its role", "to its role in", "its role in dna", "role in dna double", "in dna double strand", "dna double strand break", "strand break dsb", "signaling brca1 plays", "brca1 plays an important", "plays an important role", "an important role in", "important role in homologous", "role in homologous recombination", "in homologous recombination repair", "hrr of dsbs", "of dsbs by directly", "dsbs by directly promoting", "by directly promoting recruitment", "directly promoting recruitment of", "promoting recruitment of palb2", "recruitment of palb2 and", "of palb2 and indirectly", "palb2 and indirectly brca2", "and indirectly brca2 to", "indirectly brca2 to dsb", "brca2 to dsb repair", "to dsb repair sites.", "dsb repair sites. in", "repair sites. in addition", "in addition brca1", "addition brca1 increases", "brca1 increases the speed", "increases the speed and", "the speed and processivity", "speed and processivity of", "and processivity of dna", "processivity of dna end", "of dna end resection", "dna end resection which", "end resection which consists", "resection which consists of", "which consists of 5\u2032\u20133\u2032", "consists of 5\u2032\u20133\u2032 nucleolytic", "of 5\u2032\u20133\u2032 nucleolytic degradation", "5\u2032\u20133\u2032 nucleolytic degradation of", "nucleolytic degradation of dsbs", "of dsbs cruz", "dsbs cruz garcia", "cruz garcia et al.", "garcia et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the direct", ". the direct brca1", "the direct brca1 interaction", "direct brca1 interaction with", "brca1 interaction with palb2", "interaction with palb2 helps", "with palb2 helps to", "palb2 helps to fine", "helps to fine tune", "to fine tune the", "fine tune the localization", "tune the localization of", "the localization of brca2", "localization of brca2 and", "of brca2 and rad51", "brca2 and rad51 at", "and rad51 at dsbs", "at dsbs zhang", "dsbs zhang et", "zhang et al. 2009", "al. 2009 sy", "2009 sy et", "sy et al. 2009", "et al. 2009 .", "al. 2009 . palb2", "2009 . palb2 simultaneously", ". palb2 simultaneously interacts", "palb2 simultaneously interacts with", "simultaneously interacts with rad51", "with rad51 brca2", "rad51 brca2 and", "and rad51ap1 modesti", "rad51ap1 modesti et", "modesti et al. 2007", "al. 2007 wiese", "2007 wiese et", "wiese et al. 2007", "al. 2007 buisson", "2007 buisson et", "buisson et al. 2010", "al. 2010 dray", "2010 dray et", "dray et al. 2010", "et al. 2010 .", "al. 2010 . palb2", "2010 . palb2 and", ". palb2 and rad51ap1", "palb2 and rad51ap1 synergistically", "and rad51ap1 synergistically stimulate", "rad51ap1 synergistically stimulate rad51", "synergistically stimulate rad51 recombinase", "stimulate rad51 recombinase activity", "recombinase activity thus", "activity thus enhancing", "thus enhancing rad51 mediated", "enhancing rad51 mediated strand", "rad51 mediated strand exchange", "strand exchange branch", "exchange branch migration", "branch migration and", "migration and promoting", "and promoting the formation", "promoting the formation of", "the formation of d", "formation of d loop", "of d loop structures", "loop structures synaptic", "structures synaptic complex", "synaptic complex assembly .", "complex assembly . a", "assembly . a d", ". a d loop", "a d loop structure", "d loop structure is", "loop structure is formed", "structure is formed when", "is formed when complementary", "formed when complementary duplex", "when complementary duplex dna", "duplex dna sister", "dna sister chromatid", "chromatid arm is", "arm is progressively", "is progressively invaded by", "progressively invaded by the", "invaded by the rad51", "by the rad51 nucleoprotein", "the rad51 nucleoprotein filament", "nucleoprotein filament with", "filament with base", "with base pairing of", "base pairing of the", "pairing of the invading", "of the invading ssdna", "the invading ssdna and", "invading ssdna and the", "ssdna and the complementary", "and the complementary sister", "the complementary sister chromatid", "complementary sister chromatid dna", "sister chromatid dna strand", "dna strand sung", "strand sung et", "sung et al. 2003", "et al. 2003 .

the", "al. 2003 .

the n", "2003 .

the n terminal", ".

the n terminal region", "n terminal region of", "terminal region of brca1", "region of brca1 contains", "of brca1 contains the", "brca1 contains the ring", "contains the ring domain", "ring domain residues", "domain residues 7", "98 required", "required for the heterodimerization", "for the heterodimerization of", "the heterodimerization of brca1", "heterodimerization of brca1 with", "of brca1 with bard1.", "brca1 with bard1. brca1:bard1", "with bard1. brca1:bard1 heterodimer", "bard1. brca1:bard1 heterodimer has", "brca1:bard1 heterodimer has e3", "heterodimer has e3 ubiquitin", "has e3 ubiquitin ligase", "e3 ubiquitin ligase activity", "ubiquitin ligase activity which", "ligase activity which is", "activity which is important", "which is important for", "is important for dna", "important for dna repair", "dna repair drost", "repair drost et", "drost et al. 2011", "et al. 2011 .", "al. 2011 . several", "2011 . several missense", ". several missense mutations", "several missense mutations within", "missense mutations within the", "mutations within the ring", "within the ring domain", "the ring domain have", "ring domain have been", "domain have been linked", "have been linked to", "been linked to increased", "linked to increased risks", "to increased risks of", "increased risks of developing", "risks of developing breast/ovarian", "of developing breast/ovarian cancers", "breast/ovarian cancers bouwman", "cancers bouwman et", "bouwman et al. 2013", "al. 2013 starita", "2013 starita et", "starita et al. 2018", "et al. 2018 .", "al. 2018 . brca1", "2018 . brca1 mutant", ". brca1 mutant proteins", "brca1 mutant proteins impaired", "mutant proteins impaired in", "proteins impaired in bard1", "impaired in bard1 binding", "in bard1 binding are", "bard1 binding are annotated", "binding are annotated in", "are annotated in the", "annotated in the pathway", "in the pathway \\defective", "the pathway \\defective dna", "pathway \\defective dna double", "\\defective dna double strand", "double strand break response", "strand break response due", "break response due to", "response due to brca1", "brca1 loss of function\\.

the", "loss of function\\.

the c", "of function\\.

the c terminal", "function\\.

the c terminal region", "c terminal region of", "region of brca1 which", "of brca1 which contains", "brca1 which contains two", "which contains two coiled", "contains two coiled coil", "two coiled coil domains", "coil domains residues", "domains residues 1397", "1397 1424 and", "1424 and two", "and two brct domains", "brct domains residues", "domains residues 1642", "residues 1642 1736 for", "1642 1736 for brct", "1736 for brct 1", "brct 1 residues", "1 residues 1756", "residues 1756 1855 for", "1756 1855 for brct", "1855 for brct 2", "brct 2 is", "2 is involved", "is involved in palb2", "involved in palb2 binding", "palb2 binding with", "binding with the", "with the second coiled", "the second coiled coil", "second coiled coil domain", "coiled coil domain being", "coil domain being essential", "being essential sy", "essential sy et", "al. 2009 . several", "2009 . several cancer", ". several cancer associated", "several cancer associated brca1", "cancer associated brca1 missense", "associated brca1 missense mutants", "brca1 missense mutants that", "missense mutants that affect", "mutants that affect the", "that affect the c", "affect the c terminal", "the c terminal region", "c terminal region were", "terminal region were shown", "region were shown to", "were shown to have", "shown to have reduced", "to have reduced ability", "have reduced ability to", "reduced ability to bind", "ability to bind palb2", "bind palb2 sy", "palb2 sy et", "al. 2009 . in", "2009 . in addition", "in addition many", "addition many nonsense", "many nonsense and frameshift", "nonsense and frameshift mutations", "and frameshift mutations in", "frameshift mutations in brca1", "mutations in brca1 reported", "in brca1 reported in", "brca1 reported in cancer", "reported in cancer result", "in cancer result in", "cancer result in truncated", "result in truncated proteins", "in truncated proteins that", "truncated proteins that lack", "proteins that lack the", "that lack the palb2", "lack the palb2 binding", "the palb2 binding domain.", "in addition to its role", "addition to its role in", "to its role in dna", "its role in dna double", "role in dna double strand", "in dna double strand break", "double strand break dsb", "break dsb signaling", "dsb signaling brca1", "signaling brca1 plays an", "brca1 plays an important role", "plays an important role in", "an important role in homologous", "important role in homologous recombination", "role in homologous recombination repair", "repair hrr of", "hrr of dsbs by", "of dsbs by directly promoting", "dsbs by directly promoting recruitment", "by directly promoting recruitment of", "directly promoting recruitment of palb2", "promoting recruitment of palb2 and", "recruitment of palb2 and indirectly", "of palb2 and indirectly brca2", "palb2 and indirectly brca2 to", "and indirectly brca2 to dsb", "indirectly brca2 to dsb repair", "brca2 to dsb repair sites.", "to dsb repair sites. in", "dsb repair sites. in addition", "sites. in addition brca1", "in addition brca1 increases", "addition brca1 increases the", "brca1 increases the speed and", "increases the speed and processivity", "the speed and processivity of", "speed and processivity of dna", "and processivity of dna end", "processivity of dna end resection", "of dna end resection which", "dna end resection which consists", "end resection which consists of", "resection which consists of 5\u2032\u20133\u2032", "which consists of 5\u2032\u20133\u2032 nucleolytic", "consists of 5\u2032\u20133\u2032 nucleolytic degradation", "of 5\u2032\u20133\u2032 nucleolytic degradation of", "5\u2032\u20133\u2032 nucleolytic degradation of dsbs", "degradation of dsbs cruz", "of dsbs cruz garcia", "dsbs cruz garcia et", "cruz garcia et al. 2014", "garcia et al. 2014 .", "et al. 2014 . the", "al. 2014 . the direct", "2014 . the direct brca1", ". the direct brca1 interaction", "the direct brca1 interaction with", "direct brca1 interaction with palb2", "brca1 interaction with palb2 helps", "interaction with palb2 helps to", "with palb2 helps to fine", "palb2 helps to fine tune", "helps to fine tune the", "to fine tune the localization", "fine tune the localization of", "tune the localization of brca2", "the localization of brca2 and", "localization of brca2 and rad51", "of brca2 and rad51 at", "brca2 and rad51 at dsbs", "rad51 at dsbs zhang", "at dsbs zhang et", "dsbs zhang et al.", "et al. 2009 sy", "al. 2009 sy et", "2009 sy et al.", "sy et al. 2009 .", "et al. 2009 . palb2", "al. 2009 . palb2 simultaneously", "2009 . palb2 simultaneously interacts", ". palb2 simultaneously interacts with", "palb2 simultaneously interacts with rad51", "interacts with rad51 brca2", "with rad51 brca2 and", "rad51 brca2 and rad51ap1", "brca2 and rad51ap1 modesti", "and rad51ap1 modesti et", "rad51ap1 modesti et al.", "et al. 2007 wiese", "al. 2007 wiese et", "2007 wiese et al.", "et al. 2007 buisson", "al. 2007 buisson et", "2007 buisson et al.", "et al. 2010 dray", "al. 2010 dray et", "2010 dray et al.", "dray et al. 2010 .", "et al. 2010 . palb2", "al. 2010 . palb2 and", "2010 . palb2 and rad51ap1", ". palb2 and rad51ap1 synergistically", "palb2 and rad51ap1 synergistically stimulate", "and rad51ap1 synergistically stimulate rad51", "rad51ap1 synergistically stimulate rad51 recombinase", "synergistically stimulate rad51 recombinase activity", "rad51 recombinase activity thus", "recombinase activity thus enhancing", "activity thus enhancing rad51", "thus enhancing rad51 mediated strand", "enhancing rad51 mediated strand exchange", "mediated strand exchange branch", "strand exchange branch migration", "branch migration and promoting", "migration and promoting the", "and promoting the formation of", "promoting the formation of d", "the formation of d loop", "formation of d loop structures", "d loop structures synaptic", "loop structures synaptic complex", "structures synaptic complex assembly", "synaptic complex assembly . a", "complex assembly . a d", "assembly . a d loop", ". a d loop structure", "a d loop structure is", "d loop structure is formed", "loop structure is formed when", "structure is formed when complementary", "is formed when complementary duplex", "formed when complementary duplex dna", "complementary duplex dna sister", "duplex dna sister chromatid", "dna sister chromatid arm", "sister chromatid arm is", "chromatid arm is progressively", "arm is progressively invaded", "is progressively invaded by the", "progressively invaded by the rad51", "invaded by the rad51 nucleoprotein", "by the rad51 nucleoprotein filament", "rad51 nucleoprotein filament with", "nucleoprotein filament with base", "filament with base pairing", "with base pairing of the", "base pairing of the invading", "pairing of the invading ssdna", "of the invading ssdna and", "the invading ssdna and the", "invading ssdna and the complementary", "ssdna and the complementary sister", "and the complementary sister chromatid", "the complementary sister chromatid dna", "complementary sister chromatid dna strand", "chromatid dna strand sung", "dna strand sung et", "strand sung et al.", "sung et al. 2003 .

the", "et al. 2003 .

the n", "al. 2003 .

the n terminal", "2003 .

the n terminal region", ".

the n terminal region of", "n terminal region of brca1", "terminal region of brca1 contains", "region of brca1 contains the", "of brca1 contains the ring", "brca1 contains the ring domain", "the ring domain residues", "ring domain residues 7", "domain residues 7 98", "7 98 required", "98 required for", "required for the heterodimerization of", "for the heterodimerization of brca1", "the heterodimerization of brca1 with", "heterodimerization of brca1 with bard1.", "of brca1 with bard1. brca1:bard1", "brca1 with bard1. brca1:bard1 heterodimer", "with bard1. brca1:bard1 heterodimer has", "bard1. brca1:bard1 heterodimer has e3", "brca1:bard1 heterodimer has e3 ubiquitin", "heterodimer has e3 ubiquitin ligase", "has e3 ubiquitin ligase activity", "e3 ubiquitin ligase activity which", "ubiquitin ligase activity which is", "ligase activity which is important", "activity which is important for", "which is important for dna", "is important for dna repair", "for dna repair drost", "dna repair drost et", "repair drost et al.", "drost et al. 2011 .", "et al. 2011 . several", "al. 2011 . several missense", "2011 . several missense mutations", ". several missense mutations within", "several missense mutations within the", "missense mutations within the ring", "mutations within the ring domain", "within the ring domain have", "the ring domain have been", "ring domain have been linked", "domain have been linked to", "have been linked to increased", "been linked to increased risks", "linked to increased risks of", "to increased risks of developing", "increased risks of developing breast/ovarian", "risks of developing breast/ovarian cancers", "developing breast/ovarian cancers bouwman", "breast/ovarian cancers bouwman et", "cancers bouwman et al.", "et al. 2013 starita", "al. 2013 starita et", "2013 starita et al.", "starita et al. 2018 .", "et al. 2018 . brca1", "al. 2018 . brca1 mutant", "2018 . brca1 mutant proteins", ". brca1 mutant proteins impaired", "brca1 mutant proteins impaired in", "mutant proteins impaired in bard1", "proteins impaired in bard1 binding", "impaired in bard1 binding are", "in bard1 binding are annotated", "bard1 binding are annotated in", "binding are annotated in the", "are annotated in the pathway", "annotated in the pathway \\defective", "in the pathway \\defective dna", "the pathway \\defective dna double", "pathway \\defective dna double strand", "\\defective dna double strand break", "dna double strand break response", "double strand break response due", "strand break response due to", "break response due to brca1", "response due to brca1 loss", "to brca1 loss of function\\.

the", "brca1 loss of function\\.

the c", "loss of function\\.

the c terminal", "of function\\.

the c terminal region", "function\\.

the c terminal region of", "c terminal region of brca1", "terminal region of brca1 which", "region of brca1 which contains", "of brca1 which contains two", "brca1 which contains two coiled", "which contains two coiled coil", "contains two coiled coil domains", "coiled coil domains residues", "coil domains residues 1397", "domains residues 1397 1424", "residues 1397 1424 and", "1397 1424 and two", "1424 and two brct", "two brct domains residues", "brct domains residues 1642", "domains residues 1642 1736", "residues 1642 1736 for brct", "1642 1736 for brct 1", "for brct 1 residues", "brct 1 residues 1756", "1 residues 1756 1855", "residues 1756 1855 for brct", "1756 1855 for brct 2", "for brct 2 is", "brct 2 is involved", "2 is involved in", "is involved in palb2 binding", "in palb2 binding with", "palb2 binding with the", "binding with the second", "with the second coiled coil", "the second coiled coil domain", "second coiled coil domain being", "coiled coil domain being essential", "domain being essential sy", "being essential sy et", "essential sy et al.", "et al. 2009 . several", "al. 2009 . several cancer", "2009 . several cancer associated", ". several cancer associated brca1", "several cancer associated brca1 missense", "cancer associated brca1 missense mutants", "associated brca1 missense mutants that", "brca1 missense mutants that affect", "missense mutants that affect the", "mutants that affect the c", "that affect the c terminal", "affect the c terminal region", "the c terminal region were", "c terminal region were shown", "terminal region were shown to", "region were shown to have", "were shown to have reduced", "shown to have reduced ability", "to have reduced ability to", "have reduced ability to bind", "reduced ability to bind palb2", "to bind palb2 sy", "bind palb2 sy et", "palb2 sy et al.", "et al. 2009 . in", "al. 2009 . in addition", ". in addition many", "in addition many nonsense", "addition many nonsense and", "many nonsense and frameshift mutations", "nonsense and frameshift mutations in", "and frameshift mutations in brca1", "frameshift mutations in brca1 reported", "mutations in brca1 reported in", "in brca1 reported in cancer", "brca1 reported in cancer result", "reported in cancer result in", "in cancer result in truncated", "cancer result in truncated proteins", "result in truncated proteins that", "in truncated proteins that lack", "truncated proteins that lack the", "proteins that lack the palb2", "that lack the palb2 binding", "lack the palb2 binding domain." ] }, { "record_id": "GLY_000594_1_1", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717207", "r hsa", "hsa 9717207", "r hsa 9717207" ] }, { "record_id": "GLY_000594_1_1", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sensory perception", "perception of", "of sweet", "and umami", "sensory perception of", "perception of sweet", "sweet bitter", "bitter and", "umami glutamate", "glutamate taste", "sensory perception of sweet", "of sweet bitter", "bitter and umami", "and umami glutamate", "perception of sweet bitter", "sweet bitter and", "umami glutamate taste", "taste receptors", "receptors for", "for bitter", "bitter compounds", "sweet compounds", "umami compounds", "l glutamate", "glutamate in", "in humans", "several amino", "amino acids", "acids in", "in mice", "are g", "g protein", "protein coupled", "coupled receptors", "receptors located", "located in", "in type", "type ii", "ii taste", "taste bud", "bud cells", "cells that", "that signal", "signal through", "through a", "a common", "common downstream", "downstream pathway", "reviewed in", "in margolskee", "margolskee 2002", "kinnamon 2009", "kurihara 2015", "roper and", "and chauhari", "chauhari et", "et al.", "al. 2017", "kinnamon and", "and finger", "finger 2019", "servant et", "al. 2020", "2020 .", ". umami", "receptors are", "are heterodimers", "heterodimers of", "of the", "the plasma", "plasma membrane", "membrane proteins", "proteins tas1r1", "tas1r1 and", "and tas1r3.", "tas1r3. tas1r1:tas1r3", "tas1r1:tas1r3 heterodimers", "heterodimers also", "also bind", "bind 5'", "5' nucleotides", "nucleotides such", "such as", "as 5'", "5' imp", "imp which", "which synergistically", "synergistically augment", "augment umami", "umami taste.", "taste. the", "the glutamate", "glutamate receptors", "receptors grm1", "and grm4", "act in", "in an", "an alternative", "alternative pathway", "pathway for", "for sensing", "sensing glutamate", "in taste", "taste cells", "in chaudhari", "chaudhari et", "al. 2009", "2009 .", ". sweet", "sweet taste", "proteins tas1r2", "tas1r2 and", "and tas1r3", "in yang", "yang et", "al. 2021", "2021 .", ". the", "the glucose", "glucose transporters", "transporters sglt1", "sglt1 and", "and glut4", "glut4 are", "are expressed", "expressed in", "cells and", "and may", "may provide", "provide an", "sensing glucose", "in von", "von molitor", "molitor et", ". bitter", "bitter receptors", "are a", "a large", "large family", "family of", "of monomeric", "monomeric plasma", "the tas2r", "tas2r proteins.
", "proteins.
tas1r", "tas1r containing", "containing sweet", "sweet and", "umami receptors", "receptors and", "and tas2r", "tas2r bitter", "are each", "each physically", "physically associated", "associated with", "with a", "a particular", "particular heterotrimeric", "heterotrimeric g", "protein complex", "the gustducin", "gustducin complex", "containing gnat3", "gnb1 or", "or gnb3", "and gng13.", "gng13. upon", "upon binding", "binding an", "an agonist", "agonist ligand", "the receptor", "receptor activates", "activates the", "the alpha", "alpha subunit", "to exchange", "exchange gdp", "gdp for", "for gtp", "which results", "results in", "in a", "a conformational", "conformational change", "change in", "in gnat3", "gnat3 that", "that causes", "causes the", "receptor gustducin", "complex to", "to dissociate", "yielding gnat3:gtp", "gnb1 3:gng13", "and the", "the receptor:ligand.", "receptor:ligand. the", "the gnb1", "3:gng13 complex", "complex binds", "binds and", "and activates", "activates phospholipase", "phospholipase c", "c beta", "beta 2", "which then", "then hydrolyzes", "hydrolyzes phosphoinositol", "phosphoinositol 4", "4 5", "5 bisphosphate", "pi 4", "5 p2", "to yield", "yield diacylglycerol", "diacylglycerol and", "and inositol", "inositol 1", "1 4", "5 trisphosphate", "i 1", "5 p3", "p3 .", "p3 binds", "the calcium", "calcium channel", "channel ip3", "ip3 gated", "gated ca", "ca channel", "channel type", "type 3", "and itpr3", "itpr3 then", "then releases", "releases calcium", "calcium ions", "ions from", "from the", "the endoplasmic", "endoplasmic reticulum", "reticulum into", "into the", "the cytosol.", "cytosol. the", "the increased", "increased cytosolic", "cytosolic calcium", "calcium activates", "the trpm5", "trpm5 cation", "cation channels", "then transport", "transport sodium", "sodium ions", "ions along", "along the", "the concentration", "concentration gradient", "gradient from", "the extracellular", "extracellular region", "region to", "to the", "the cytosol", "in aroke", "aroke et", "the depolarization", "depolarization activates", "activates scn2a", "and scn9a", "scn9a channels", "which transport", "transport further", "further sodium", "depolarization of", "membrane opens", "opens calhm1:calhm3", "calhm1:calhm3 channels", "transport atp", "a neurotransmitter", "neurotransmitter in", "in the", "the olfactory", "olfactory system", "cytosol to", "extracellular region.
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", "tas2r proteins.
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taste", "extracellular region.
taste receptors", "region.
taste receptors were", "receptors were initially", "were initially discovered", "initially discovered in", "discovered in taste", "in taste buds", "taste buds of", "buds of the", "of the tongue", "the tongue and", "tongue and have", "and have now", "have now been", "now been found", "been found in", "found in several", "in several other", "several other tissues", "other tissues including", "tissues including nasal", "including nasal epithelium", "epithelium barnham", "barnham et al.", "et al. 2015", "2015 inferred", "inferred from rodent", "from rodent homologs", "rodent homologs in", "homologs in tizzano", "in tizzano et", "tizzano et al.", "et al. 2011", "the respiratory system", "system pancreatic", "pancreatic islet cells", "cells sperm", "sperm governini", "governini et al.", "leukocytes malki", "malki et al.", "and enteroendocrine cells", "enteroendocrine cells of", "cells of the", "of the gut", "gut inferred", "inferred from rat", "from rat and", "rat and mouse", "and mouse homologs", "mouse homologs in", "homologs in wu", "in wu et", "wu et al.", "et al. 2002", "al. 2002 .", "taste receptors for bitter", "receptors for bitter compounds", "bitter compounds sweet", "compounds sweet compounds", "sweet compounds and", "compounds and umami", "umami compounds l", "compounds l glutamate", "l glutamate in humans", "in humans several", "humans several amino", "several amino acids in", "amino acids in mice", "in mice are", "mice are g", "are g protein coupled", "g protein coupled receptors", "protein coupled receptors located", "coupled receptors located in", "receptors located in type", "located in type ii", "in type ii taste", "type ii taste bud", "ii taste bud cells", "taste bud cells that", "bud cells that signal", "cells that signal through", "that signal through a", "signal through a common", "through a common downstream", "a common downstream pathway", "downstream pathway reviewed", "pathway reviewed in", "reviewed in margolskee 2002", "margolskee 2002 kinnamon", "2002 kinnamon 2009", "kinnamon 2009 kurihara", "2009 kurihara 2015", "kurihara 2015 roper", "2015 roper and", "roper and chauhari et", "and chauhari et al.", "chauhari et al. 2017", "al. 2017 kinnamon", "2017 kinnamon and", "kinnamon and finger 2019", "finger 2019 servant", "2019 servant et", "servant et al. 2020", "et al. 2020 .", "al. 2020 . umami", ". umami \\savoury\\", "\\savoury\\ l glutamate", "l glutamate taste", "glutamate taste receptors", "taste receptors are heterodimers", "receptors are heterodimers of", "are heterodimers of the", "heterodimers of the plasma", "of the plasma membrane", "the plasma membrane proteins", "plasma membrane proteins tas1r1", "membrane proteins tas1r1 and", "proteins tas1r1 and tas1r3.", "tas1r1 and tas1r3. tas1r1:tas1r3", "and tas1r3. tas1r1:tas1r3 heterodimers", "tas1r3. tas1r1:tas1r3 heterodimers also", "tas1r1:tas1r3 heterodimers also bind", "heterodimers also bind 5'", "also bind 5' nucleotides", "bind 5' nucleotides such", "5' nucleotides such as", "nucleotides such as 5'", "such as 5' imp", "as 5' imp which", "5' imp which synergistically", "imp which synergistically augment", "which synergistically augment umami", "synergistically augment umami taste.", "augment umami taste. the", "umami taste. the glutamate", "taste. the glutamate receptors", "the glutamate receptors grm1", "receptors grm1 mglur1", "mglur1 and grm4", "and grm4 mglur4", "mglur4 act in", "act in an alternative", "in an alternative pathway", "an alternative pathway for", "alternative pathway for sensing", "pathway for sensing glutamate", "for sensing glutamate in", "sensing glutamate in taste", "glutamate in taste cells", "taste cells reviewed", "cells reviewed in", "reviewed in chaudhari et", "in chaudhari et al.", "chaudhari et al. 2009", "et al. 2009 .", "al. 2009 . sweet", "2009 . sweet taste", ". sweet taste receptors", "sweet taste receptors are", "plasma membrane proteins tas1r2", "membrane proteins tas1r2 and", "proteins tas1r2 and tas1r3", "and tas1r3 reviewed", "tas1r3 reviewed in", "reviewed in yang et", "in yang et al.", "yang et al. 2021", "et al. 2021 .", "al. 2021 . the", "2021 . the glucose", ". the glucose transporters", "the glucose transporters sglt1", "glucose transporters sglt1 and", "transporters sglt1 and glut4", "sglt1 and glut4 are", "and glut4 are expressed", "glut4 are expressed in", "are expressed in type", "expressed in type ii", "type ii taste cells", "ii taste cells and", "taste cells and may", "cells and may provide", "and may provide an", "may provide an alternative", "provide an alternative pathway", "pathway for sensing glucose", "sensing glucose reviewed", "glucose reviewed in", "reviewed in von molitor", "in von molitor et", "von molitor et al.", "molitor et al. 2020", "al. 2020 . bitter", "2020 . bitter receptors", ". bitter receptors are", "bitter receptors are a", "receptors are a large", "are a large family", "a large family of", "large family of monomeric", "family of monomeric plasma", "of monomeric plasma membrane", "monomeric plasma membrane proteins", "membrane proteins the", "proteins the tas2r", "the tas2r proteins.
tas1r", "tas2r proteins.
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tas1r containing sweet", "tas1r containing sweet and", "containing sweet and umami", "sweet and umami receptors", "and umami receptors and", "umami receptors and tas2r", "receptors and tas2r bitter", "and tas2r bitter receptors", "tas2r bitter receptors are", "bitter receptors are each", "receptors are each physically", "are each physically associated", "each physically associated with", "physically associated with a", "associated with a particular", "with a particular heterotrimeric", "a particular heterotrimeric g", "particular heterotrimeric g protein", "heterotrimeric g protein complex", "protein complex the", "complex the gustducin", "gustducin complex containing", "complex containing gnat3", "containing gnat3 gustducin", "gustducin gnb1", "or gnb3 and", "gnb3 and gng13.", "and gng13. upon binding", "gng13. upon binding an", "upon binding an agonist", "binding an agonist ligand", "agonist ligand the", "ligand the receptor", "the receptor activates the", "receptor activates the alpha", "activates the alpha subunit", "alpha subunit gnat3", "gnat3 to exchange", "to exchange gdp for", "exchange gdp for gtp", "for gtp which", "gtp which results", "which results in a", "results in a conformational", "in a conformational change", "a conformational change in", "conformational change in gnat3", "change in gnat3 that", "in gnat3 that causes", "gnat3 that causes the", "that causes the receptor", "causes the receptor gustducin", "the receptor gustducin complex", "receptor gustducin complex to", "gustducin complex to dissociate", "to dissociate yielding", "dissociate yielding gnat3:gtp", "yielding gnat3:gtp gnb1", "gnat3:gtp gnb1 3:gng13", "gnb1 3:gng13 and", "3:gng13 and the", "and the receptor:ligand. the", "the receptor:ligand. the gnb1", "receptor:ligand. the gnb1 3:gng13", "the gnb1 3:gng13 complex", "gnb1 3:gng13 complex binds", "3:gng13 complex binds and", "complex binds and activates", "binds and activates phospholipase", "and activates phospholipase c", "activates phospholipase c beta", "phospholipase c beta 2", "beta 2 plcb2", "plcb2 which", "which then hydrolyzes phosphoinositol", "then hydrolyzes phosphoinositol 4", "hydrolyzes phosphoinositol 4 5", "phosphoinositol 4 5 bisphosphate", "5 bisphosphate pi", "bisphosphate pi 4", "pi 4 5 p2", "5 p2 to", "p2 to yield", "to yield diacylglycerol and", "yield diacylglycerol and inositol", "diacylglycerol and inositol 1", "and inositol 1 4", "inositol 1 4 5", "1 4 5 trisphosphate", "5 trisphosphate i", "trisphosphate i 1", "i 1 4 5", "1 4 5 p3", "4 5 p3 .", "p3 . i", ". i 1", "4 5 p3 binds", "5 p3 binds and", "p3 binds and activates", "binds and activates the", "and activates the calcium", "activates the calcium channel", "the calcium channel ip3", "calcium channel ip3 gated", "channel ip3 gated ca", "ip3 gated ca channel", "gated ca channel type", "ca channel type 3", "type 3 itpr3", "itpr3 and itpr3", "and itpr3 then releases", "itpr3 then releases calcium", "then releases calcium ions", "releases calcium ions from", "calcium ions from the", "ions from the endoplasmic", "from the endoplasmic reticulum", "the endoplasmic reticulum into", "endoplasmic reticulum into the", "reticulum into the cytosol.", "into the cytosol. the", "the cytosol. the increased", "cytosol. the increased cytosolic", "the increased cytosolic calcium", "increased cytosolic calcium activates", "cytosolic calcium activates the", "calcium activates the trpm5", "activates the trpm5 cation", "the trpm5 cation channels", "cation channels which", "channels which then", "which then transport sodium", "then transport sodium ions", "transport sodium ions along", "sodium ions along the", "ions along the concentration", "along the concentration gradient", "the concentration gradient from", "concentration gradient from the", "gradient from the extracellular", "from the extracellular region", "the extracellular region to", "extracellular region to the", "region to the cytosol", "the cytosol reviewed", "cytosol reviewed in", "reviewed in aroke et", "in aroke et al.", "aroke et al. 2020", "al. 2020 . the", "2020 . the depolarization", ". the depolarization activates", "the depolarization activates scn2a", "activates scn2a scn3a", "scn3a and scn9a", "scn9a channels which", "channels which transport", "which transport further sodium", "transport further sodium ions", "further sodium ions from", "sodium ions from the", "ions from the extracellular", "region to the cytosol.", "to the cytosol. the", "the cytosol. the depolarization", "cytosol. the depolarization of", "the depolarization of the", "depolarization of the plasma", "the plasma membrane opens", "plasma membrane opens calhm1:calhm3", "membrane opens calhm1:calhm3 channels", "calhm1:calhm3 channels which", "transport atp a", "atp a neurotransmitter", "a neurotransmitter in the", "neurotransmitter in the olfactory", "in the olfactory system", "olfactory system from", "system from the", "from the cytosol to", "the cytosol to the", "cytosol to the extracellular", "to the extracellular region.
taste", "the extracellular region.
taste receptors", "extracellular region.
taste receptors were", "region.
taste receptors were initially", "receptors were initially discovered", "were initially discovered in", "initially discovered in taste", "discovered in taste buds", "in taste buds of", "taste buds of the", "buds of the tongue", "of the tongue and", "the tongue and have", "tongue and have now", "and have now been", "have now been found", "now been found in", "been found in several", "found in several other", "in several other tissues", "several other tissues including", "other tissues including nasal", "tissues including nasal epithelium", "nasal epithelium barnham", "epithelium barnham et", "barnham et al. 2015", "al. 2015 inferred", "2015 inferred from", "inferred from rodent homologs", "from rodent homologs in", "rodent homologs in tizzano", "homologs in tizzano et", "in tizzano et al.", "tizzano et al. 2011", "2011 the", "respiratory system pancreatic", "system pancreatic islet", "islet cells sperm", "sperm governini et", "governini et al. 2020", "2020 leukocytes", "leukocytes malki et", "malki et al. 2015", "2015 and", "and enteroendocrine cells of", "enteroendocrine cells of the", "cells of the gut", "the gut inferred", "gut inferred from", "inferred from rat and", "from rat and mouse", "rat and mouse homologs", "and mouse homologs in", "mouse homologs in wu", "homologs in wu et", "in wu et al.", "wu et al. 2002", "et al. 2002 .", "taste receptors for bitter compounds", "for bitter compounds sweet", "bitter compounds sweet compounds", "sweet compounds and umami", "compounds and umami compounds", "and umami compounds l", "umami compounds l glutamate", "compounds l glutamate in", "glutamate in humans several", "in humans several amino", "humans several amino acids", "several amino acids in mice", "acids in mice are", "in mice are g", "mice are g protein", "are g protein coupled receptors", "g protein coupled receptors located", "protein coupled receptors located in", "coupled receptors located in type", "receptors located in type ii", "located in type ii taste", "in type ii taste bud", "type ii taste bud cells", "ii taste bud cells that", "taste bud cells that signal", "bud cells that signal through", "cells that signal through a", "that signal through a common", "signal through a common downstream", "through a common downstream pathway", "common downstream pathway reviewed", "downstream pathway reviewed in", "pathway reviewed in margolskee", "in margolskee 2002 kinnamon", "margolskee 2002 kinnamon 2009", "kinnamon 2009 kurihara 2015", "kurihara 2015 roper and", "2015 roper and chauhari", "roper and chauhari et al.", "and chauhari et al. 2017", "et al. 2017 kinnamon", "al. 2017 kinnamon and", "2017 kinnamon and finger", "and finger 2019 servant", "finger 2019 servant et", "2019 servant et al.", "servant et al. 2020 .", "et al. 2020 . umami", "2020 . umami \\savoury\\", "umami \\savoury\\ l", "l glutamate taste receptors", "glutamate taste receptors are", "taste receptors are heterodimers of", "receptors are heterodimers of the", "are heterodimers of the plasma", "heterodimers of the plasma membrane", "of the plasma membrane proteins", "the plasma membrane proteins tas1r1", "plasma membrane proteins tas1r1 and", "membrane proteins tas1r1 and tas1r3.", "proteins tas1r1 and tas1r3. tas1r1:tas1r3", "tas1r1 and tas1r3. tas1r1:tas1r3 heterodimers", "and tas1r3. tas1r1:tas1r3 heterodimers also", "tas1r3. tas1r1:tas1r3 heterodimers also bind", "tas1r1:tas1r3 heterodimers also bind 5'", "heterodimers also bind 5' nucleotides", "also bind 5' nucleotides such", "bind 5' nucleotides such as", "5' nucleotides such as 5'", "nucleotides such as 5' imp", "such as 5' imp which", "as 5' imp which synergistically", "5' imp which synergistically augment", "imp which synergistically augment umami", "which synergistically augment umami taste.", "synergistically augment umami taste. the", "augment umami taste. the glutamate", "umami taste. the glutamate receptors", "taste. the glutamate receptors grm1", "glutamate receptors grm1 mglur1", "grm1 mglur1 and", "grm4 mglur4 act", "mglur4 act in an", "act in an alternative pathway", "in an alternative pathway for", "an alternative pathway for sensing", "alternative pathway for sensing glutamate", "pathway for sensing glutamate in", "for sensing glutamate in taste", "sensing glutamate in taste cells", "in taste cells reviewed", "taste cells reviewed in", "cells reviewed in chaudhari", "reviewed in chaudhari et al.", "in chaudhari et al. 2009", "chaudhari et al. 2009 .", "et al. 2009 . sweet", "al. 2009 . sweet taste", "2009 . sweet taste receptors", ". sweet taste receptors are", "sweet taste receptors are heterodimers", "the plasma membrane proteins tas1r2", "plasma membrane proteins tas1r2 and", "membrane proteins tas1r2 and tas1r3", "tas1r2 and tas1r3 reviewed", "and tas1r3 reviewed in", "tas1r3 reviewed in yang", "reviewed in yang et al.", "in yang et al. 2021", "yang et al. 2021 .", "et al. 2021 . the", "al. 2021 . the glucose", "2021 . the glucose transporters", ". the glucose transporters sglt1", "the glucose transporters sglt1 and", "glucose transporters sglt1 and glut4", "transporters sglt1 and glut4 are", "sglt1 and glut4 are expressed", "and glut4 are expressed in", "glut4 are expressed in type", "are expressed in type ii", "expressed in type ii taste", "in type ii taste cells", "type ii taste cells and", "ii taste cells and may", "taste cells and may provide", "cells and may provide an", "and may provide an alternative", "may provide an alternative pathway", "provide an alternative pathway for", "alternative pathway for sensing glucose", "for sensing glucose reviewed", "sensing glucose reviewed in", "glucose reviewed in von", "reviewed in von molitor et", "in von molitor et al.", "von molitor et al. 2020", "molitor et al. 2020 .", "et al. 2020 . bitter", "al. 2020 . bitter receptors", "2020 . bitter receptors are", ". bitter receptors are a", "bitter receptors are a large", "receptors are a large family", "are a large family of", "a large family of monomeric", "large family of monomeric plasma", "family of monomeric plasma membrane", "of monomeric plasma membrane proteins", "plasma membrane proteins the", "membrane proteins the tas2r", "proteins the tas2r proteins.
", "the tas2r proteins.
tas1r containing", "tas2r proteins.
tas1r containing sweet", "proteins.
tas1r containing sweet and", "tas1r containing sweet and umami", "containing sweet and umami receptors", "sweet and umami receptors and", "and umami receptors and tas2r", "umami receptors and tas2r bitter", "receptors and tas2r bitter receptors", "and tas2r bitter receptors are", "tas2r bitter receptors are each", "bitter receptors are each physically", "receptors are each physically associated", "are each physically associated with", "each physically associated with a", "physically associated with a particular", "associated with a particular heterotrimeric", "with a particular heterotrimeric g", "a particular heterotrimeric g protein", "particular heterotrimeric g protein complex", "g protein complex the", "protein complex the gustducin", "complex the gustducin complex", "the gustducin complex containing", "gustducin complex containing gnat3", "gustducin gnb1 or", "gnb1 or gnb3 and", "or gnb3 and gng13.", "gnb3 and gng13. upon", "and gng13. upon binding an", "gng13. upon binding an agonist", "upon binding an agonist ligand", "an agonist ligand the", "agonist ligand the receptor", "ligand the receptor activates", "the receptor activates the alpha", "receptor activates the alpha subunit", "the alpha subunit gnat3", "subunit gnat3 to", "gnat3 to exchange gdp", "to exchange gdp for gtp", "gdp for gtp which", "for gtp which results", "gtp which results in", "which results in a conformational", "results in a conformational change", "in a conformational change in", "a conformational change in gnat3", "conformational change in gnat3 that", "change in gnat3 that causes", "in gnat3 that causes the", "gnat3 that causes the receptor", "that causes the receptor gustducin", "causes the receptor gustducin complex", "the receptor gustducin complex to", "receptor gustducin complex to dissociate", "complex to dissociate yielding", "to dissociate yielding gnat3:gtp", "yielding gnat3:gtp gnb1 3:gng13", "gnb1 3:gng13 and the", "3:gng13 and the receptor:ligand.", "and the receptor:ligand. the gnb1", "the receptor:ligand. the gnb1 3:gng13", "receptor:ligand. the gnb1 3:gng13 complex", "the gnb1 3:gng13 complex binds", "gnb1 3:gng13 complex binds and", "3:gng13 complex binds and activates", "complex binds and activates phospholipase", "binds and activates phospholipase c", "and activates phospholipase c beta", "activates phospholipase c beta 2", "c beta 2 plcb2", "plcb2 which then", "which then hydrolyzes phosphoinositol 4", "then hydrolyzes phosphoinositol 4 5", "hydrolyzes phosphoinositol 4 5 bisphosphate", "4 5 bisphosphate pi", "5 bisphosphate pi 4", "bisphosphate pi 4 5", "4 5 p2 to", "5 p2 to yield", "p2 to yield diacylglycerol", "to yield diacylglycerol and inositol", "yield diacylglycerol and inositol 1", "diacylglycerol and inositol 1 4", "and inositol 1 4 5", "inositol 1 4 5 trisphosphate", "4 5 trisphosphate i", "5 trisphosphate i 1", "trisphosphate i 1 4", "i 1 4 5 p3", "1 4 5 p3 .", "5 p3 . i", "p3 . i 1", ". i 1 4", "1 4 5 p3 binds", "4 5 p3 binds and", "5 p3 binds and activates", "p3 binds and activates the", "binds and activates the calcium", "and activates the calcium channel", "activates the calcium channel ip3", "the calcium channel ip3 gated", "calcium channel ip3 gated ca", "channel ip3 gated ca channel", "ip3 gated ca channel type", "gated ca channel type 3", "channel type 3 itpr3", "3 itpr3 and", "itpr3 and itpr3 then", "and itpr3 then releases calcium", "itpr3 then releases calcium ions", "then releases calcium ions from", "releases calcium ions from the", "calcium ions from the endoplasmic", "ions from the endoplasmic reticulum", "from the endoplasmic reticulum into", "the endoplasmic reticulum into the", "endoplasmic reticulum into the cytosol.", "reticulum into the cytosol. the", "into the cytosol. the increased", "the cytosol. the increased cytosolic", "cytosol. the increased cytosolic calcium", "the increased cytosolic calcium activates", "increased cytosolic calcium activates the", "cytosolic calcium activates the trpm5", "calcium activates the trpm5 cation", "activates the trpm5 cation channels", "trpm5 cation channels which", "cation channels which then", "channels which then transport", "which then transport sodium ions", "then transport sodium ions along", "transport sodium ions along the", "sodium ions along the concentration", "ions along the concentration gradient", "along the concentration gradient from", "the concentration gradient from the", "concentration gradient from the extracellular", "gradient from the extracellular region", "from the extracellular region to", "the extracellular region to the", "extracellular region to the cytosol", "to the cytosol reviewed", "the cytosol reviewed in", "cytosol reviewed in aroke", "reviewed in aroke et al.", "in aroke et al. 2020", "aroke et al. 2020 .", "et al. 2020 . the", "al. 2020 . the depolarization", "2020 . the depolarization activates", ". the depolarization activates scn2a", "depolarization activates scn2a scn3a", "scn2a scn3a and", "scn3a and scn9a channels", "and scn9a channels which", "scn9a channels which transport", "channels which transport further", "which transport further sodium ions", "transport further sodium ions from", "further sodium ions from the", "sodium ions from the extracellular", "ions from the extracellular region", "extracellular region to the cytosol.", "region to the cytosol. the", "to the cytosol. the depolarization", "the cytosol. the depolarization of", "cytosol. the depolarization of the", "the depolarization of the plasma", "depolarization of the plasma membrane", "of the plasma membrane opens", "the plasma membrane opens calhm1:calhm3", "plasma membrane opens calhm1:calhm3 channels", "opens calhm1:calhm3 channels which", "calhm1:calhm3 channels which transport", "channels which transport atp", "which transport atp a", "transport atp a neurotransmitter", "atp a neurotransmitter in", "a neurotransmitter in the olfactory", "neurotransmitter in the olfactory system", "the olfactory system from", "olfactory system from the", "system from the cytosol", "from the cytosol to the", "the cytosol to the extracellular", "cytosol to the extracellular region.
taste", "to the extracellular region.
taste receptors", "the extracellular region.
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taste receptors were initially", "region.
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"in frame deletion mutations", "deletion mutations pdgfra", "mutations pdgfra and", "pdgfra and pdgfrb are", "and pdgfrb are also", "pdgfrb are also subject", "are also subject to", "also subject to low", "subject to low frequency", "to low frequency gene", "low frequency gene fusion", "frequency gene fusion events", "gene fusion events arising", "fusion events arising from", "events arising from chromosomal", "arising from chromosomal rearrangements.", "from chromosomal rearrangements. to", "chromosomal rearrangements. to date", "rearrangements. to date there", "to date there are", "date there are about", "there are about 35", "are about 35 identified", "about 35 identified pdgfra", "35 identified pdgfra or", "identified pdgfra or b", "pdgfra or b fusion", "or b fusion partners", "fusion partners with", "partners with pdgfrb", "with pdgfrb being the", "pdgfrb being the more", "being the more common", "the more common partner", "common partner reviewed", "partner reviewed in", "reviewed in appiah kubi", "in appiah kubi et", "appiah kubi et al", "et al 2017", "al 2017 .", "2017 . although some", ". although some of", "although some of the", "some of the pdgf", "of the pdgf fusions", "the pdgf fusions proteins", "pdgf fusions proteins are", "fusions proteins are cytosolic", "proteins are cytosolic by", "are cytosolic by virtue", "cytosolic by virtue of", "by virtue of removal", "virtue of removal of", "of removal of the", "removal of the pdgfr", "of the pdgfr transmembrane", "the pdgfr transmembrane region", "transmembrane region tmd", "tmd a", "a number of fusions", "number of fusions retain", "of fusions retain the", "fusions retain the tmd", "retain the tmd and", "the tmd and are", "tmd and are linked", "and are linked to", "are linked to the", "linked to the plasma", "to the plasma membrane", "plasma membrane hidalgo", "membrane hidalgo curtis", "hidalgo curtis et al", "et al 2010", "2010 ozawa et", "2010 curtis et", "et al 2007", "2007 medves et", "2010 reviewed in", "2017 . the most", ". the most common", "the most common transmembrane", "most common transmembrane fusion", "common transmembrane fusion partner", "transmembrane fusion partner of", "fusion partner of pdgfra", "partner of pdgfra and", "of pdgfra and pdgfrb", "pdgfra and pdgfrb is", "and pdgfrb is etv6", "is etv6 also", "etv6 also known", "also known as tel1", "tel1 a", "a transcriptional repressor with", "transcriptional repressor with known", "repressor with known ability", "with known ability to", "known ability to homodimerize", "to homodimerize curtis", "homodimerize curtis et", "2007 golub et", "et al 1994", "1994 andrae et", "et al 2008", "2008 reviewed in", "reviewed in de braekeleer", "in de braekeleer et", "de braekeleer et al", "et al 2012", "2012 wang et", "et al 2016", "2016 appiah kubi", "in addition to activating missensse", "addition to activating missensse and", "to activating missensse and in", "activating missensse and in frame", "missensse and in frame deletion", "and in frame deletion mutations", "frame deletion mutations pdgfra", "deletion mutations pdgfra and", "mutations pdgfra and pdgfrb", "pdgfra and pdgfrb are also", "and pdgfrb are also subject", "pdgfrb are also subject to", "are also subject to low", "also subject to low frequency", "subject to low frequency gene", "to low frequency gene fusion", "low frequency gene fusion events", "frequency gene fusion events arising", "gene fusion events arising from", "fusion events arising from chromosomal", "events arising from chromosomal rearrangements.", "arising from chromosomal rearrangements. to", "from chromosomal rearrangements. to date", "chromosomal rearrangements. to date there", "rearrangements. to date there are", "to date there are about", "date there are about 35", "there are about 35 identified", "are about 35 identified pdgfra", "about 35 identified pdgfra or", "35 identified pdgfra or b", "identified pdgfra or b fusion", "pdgfra or b fusion partners", "b fusion partners with", "fusion partners with pdgfrb", "partners with pdgfrb being", "with pdgfrb being the more", "pdgfrb being the more common", "being the more common partner", "more common partner reviewed", "common partner reviewed in", "partner reviewed in appiah", "reviewed in appiah kubi et", "in appiah kubi et al", "kubi et al 2017", "et al 2017 .", "al 2017 . although", "2017 . although some of", ". although some of the", "although some of the pdgf", "some of the pdgf fusions", "of the pdgf fusions proteins", "the pdgf fusions proteins are", "pdgf fusions proteins are cytosolic", "fusions proteins are cytosolic by", "proteins are cytosolic by virtue", "are cytosolic by virtue of", "cytosolic by virtue of removal", "by virtue of removal of", "virtue of removal of the", "of removal of the pdgfr", "removal of the pdgfr transmembrane", "of the pdgfr transmembrane region", "pdgfr transmembrane region tmd", "tmd a number", "a number of fusions retain", "number of fusions retain the", "of fusions retain the tmd", "fusions retain the tmd and", "retain the tmd and are", "the tmd and are linked", "tmd and are linked to", "and are linked to the", "are linked to the plasma", "linked to the plasma membrane", "the plasma membrane hidalgo", "plasma membrane hidalgo curtis", "membrane hidalgo curtis et", "curtis et al 2010", "al 2010 ozawa", "2010 ozawa et al", "ozawa et al 2010", "al 2010 curtis", "2010 curtis et al", "curtis et al 2007", "al 2007 medves", "2007 medves et al", "medves et al 2010", "al 2010 reviewed", "2010 reviewed in appiah", "al 2017 . the", "2017 . the most common", ". the most common transmembrane", "the most common transmembrane fusion", "most common transmembrane fusion partner", "common transmembrane fusion partner of", "transmembrane fusion partner of pdgfra", "fusion partner of pdgfra and", "partner of pdgfra and pdgfrb", "of pdgfra and pdgfrb is", "pdgfra and pdgfrb is etv6", "pdgfrb is etv6 also", "is etv6 also known", "etv6 also known as", "as tel1 a", "tel1 a transcriptional", "a transcriptional repressor with known", "transcriptional repressor with known ability", "repressor with known ability to", "with known ability to homodimerize", "ability to homodimerize curtis", "to homodimerize curtis et", "homodimerize curtis et al", "al 2007 golub", "2007 golub et al", "golub et al 1994", "al 1994 andrae", "1994 andrae et al", "andrae et al 2008", "al 2008 reviewed", "2008 reviewed in de", "reviewed in de braekeleer et", "in de braekeleer et al", "braekeleer et al 2012", "al 2012 wang", "2012 wang et al", "wang et al 2016", "al 2016 appiah", "2016 appiah kubi et" ] }, { "record_id": "GLY_000594_1_6", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9683610", "r hsa", "hsa 9683610", "r hsa 9683610" ] }, { "record_id": "GLY_000594_1_6", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "maturation of", "of nucleoprotein", "maturation of 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27", "27 leukemia", "leukemia inhibitory", "inhibitory factor", "cilliary neurotrophic", "neurotrophic factor", "and oncostatin", "oncostatin m.", "m.

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the il", "6 receptor", "consists of", "of an", "an alpha", "alpha subunit", "subunit that", "that specifically", "specifically binds", "binds il", "6 and", "and a", "a beta", "beta subunit", "il6rb or", "or gp130", "which is", "the signaling", "signaling component", "component of", "of all", "all the", "the receptors", "receptors for", "for cytokines", "cytokines related", "related to", "to il", "il 6.", "6. il6r", "il6r alpha", "alpha exists", "exists in", "in transmembrane", "transmembrane and", "and soluble", "soluble forms.", "forms. the", "the transmembrane", "transmembrane form", "form is", "is mainly", "mainly expressed", "expressed by", "by hepatocytes", "and some", "some lymphocytes.", "lymphocytes. soluble", "soluble forms", "forms of", "of il6r", "are also", "also expressed", "by these", "these cells.", "cells. two", "two major", "major mechanisms", "mechanisms for", "for the", "the production", "production of", "of sil6r", "sil6r have", "have been", "been proposed.", "proposed. alternative", "alternative splicing", "splicing generates", "generates a", "a transcript", "transcript lacking", "lacking the", "transmembrane domain", "domain by", "by using", "using splicing", "splicing donor", "donor and", "and acceptor", "acceptor sites", "sites that", "that flank", "flank the", "domain coding", "coding region.", "region. this", "this also", "also introduces", "introduces a", "a frameshift", "frameshift leading", "leading to", "to the", "the incorporation", "incorporation of", "of 10", "10 additional", "additional amino", "amino acids", "acids at", "at the", "the c", "c terminus", "terminus of", "of sil6r.a", "sil6r.a second", "second mechanism", "mechanism for", "the generation", "generation of", "sil6r is", "the proteolytic", "proteolytic cleavage", "cleavage or", "or 'shedding'", "'shedding' of", "of membrane", "membrane bound", "bound il", "il 6r.", "6r. two", "two proteases", "proteases adam10", "adam10 and", "and adam17", "adam17 are", "are thought", "thought to", "to contribute", "contribute to", "to this", "briso et", "et al.", "al. 2008", "2008 .", ". sil6r", "sil6r can", "can bind", "bind il6", "il6 and", "and stimulate", "stimulate cells", "cells that", "that express", "express gp130", "gp130 but", "but not", "not il6r", "a process", "process that", "that is", "is termed", "termed trans", "trans signaling.", "signaling. this", "this explains", "explains why", "why many", "many cells", "including hematopoietic", "hematopoietic progenitor", "progenitor cells", "neuronal cells", "endothelial cells", "smooth muscle", "muscle cells", "and embryonic", "embryonic stem", "stem cells", "do not", "not respond", "respond to", "to il6", "il6 alone", "but show", "show a", "a remarkable", "remarkable response", "response to", "to il6/sil6r.", "il6/sil6r. it", "is clear", "clear that", "that the", "the trans", "trans signaling", "signaling pathway", "pathway is", "is responsible", "responsible for", "the pro", "pro inflammatory", "inflammatory activities", "activities of", "6 whereas", "whereas the", "the membrane", "bound receptor", "receptor governs", "governs regenerative", "regenerative and", "and anti", "anti inflammatory", "inflammatory il", "6 activities

il6r", "activities

il6r signal", "signal transduction", "transduction is", "is mediated", "mediated by", "by two", "two pathways:the", "pathways:the jak", "jak stat", "janus family", "family tyrosine", "tyrosine kinase", "kinase signal", "signal transducer", "transducer and", "and activator", "activator of", "of transcription", "pathway and", "and the", "the ras", "ras mapk", "mitogen activated", "activated protein", "protein kinase", "pathway. negative", "negative regulators", "regulators of", "signaling include", "include socs", "suppressor of", "of cytokine", "cytokine signals", "and shp2.", "shp2. within", "within the", "the last", "last few", "few years", "years different", "different antibodies", "antibodies have", "been developed", "developed to", "to inhibit", "inhibit il", "6 activity", "the first", "first such", "such antibodies", "been introduced", "introduced into", "into the", "the clinic", "clinic for", "the treatment", "treatment of", "of inflammatory", "inflammatory diseases", "kopf et", "al. 2010", "2010 .", "6 il", "6 is", "is a pleiotropic", "a pleiotropic cytokine", "pleiotropic cytokine with", "cytokine with roles", "with roles in", "roles in processes", "in processes including", "processes including immune", "including immune regulation", "regulation hematopoiesis", "hematopoiesis inflammation", "inflammation oncogenesis", "oncogenesis metabolic", "metabolic control and", "control and sleep.", "sleep. it", "it is the", "is the founding", "the founding member", "founding member of", "member of a", "of a family", "a family of", "family of il", "of il 6", "il 6 related", "6 related cytokines", "related cytokines such", "cytokines such as", "such as il", "as il 11", "11 il", "il 27 leukemia", "27 leukemia inhibitory", "leukemia inhibitory factor", "factor lif", "cilliary neurotrophic factor", "factor cntf", "cntf and", "and oncostatin m.", "oncostatin m.

the", "m.

the il", "

the il 6", "il 6 receptor", "receptor il6r", "il6r consists", "consists of an", "of an alpha", "an alpha subunit", "alpha subunit that", "subunit that specifically", "that specifically binds", "specifically binds il", "binds il 6", "il 6 and", "6 and a", "and a beta", "a beta subunit", "subunit il6rb", "il6rb or gp130", "gp130 which", "which is the", "is the signaling", "the signaling component", "signaling component of", "component of all", "of all the", "all the receptors", "the receptors for", "receptors for cytokines", "for cytokines related", "cytokines related to", "related to il", "to il 6.", "il 6. il6r", "6. il6r alpha", "il6r alpha exists", "alpha exists in", "exists in transmembrane", "in transmembrane and", "transmembrane and soluble", "and soluble forms.", "soluble forms. the", "forms. the transmembrane", "the transmembrane form", "transmembrane form is", "form is mainly", "is mainly expressed", "mainly expressed by", "expressed by hepatocytes", "hepatocytes neutrophils", "neutrophils monocytes/macrophages", "monocytes/macrophages and", "and some lymphocytes.", "some lymphocytes. soluble", "lymphocytes. soluble forms", "soluble forms of", "forms of il6r", "il6r sil6r", "sil6r are", "are also expressed", "also expressed by", "expressed by these", "by these cells.", "these cells. two", "cells. two major", "two major mechanisms", "major mechanisms for", "mechanisms for the", "for the production", "the production of", "production of sil6r", "of sil6r have", "sil6r have been", "have been proposed.", "been proposed. alternative", "proposed. alternative splicing", "alternative splicing generates", "splicing generates a", "generates a transcript", "a transcript lacking", "transcript lacking the", "lacking the transmembrane", "the transmembrane domain", "transmembrane domain by", "domain by using", "by using splicing", "using splicing donor", "splicing donor and", "donor and acceptor", "and acceptor sites", "acceptor sites that", "sites that flank", "that flank the", "flank the transmembrane", "transmembrane domain coding", "domain coding region.", "coding region. this", "region. this also", "this also introduces", "also introduces a", "introduces a frameshift", "a frameshift leading", "frameshift leading to", "leading to the", "to the incorporation", "the incorporation of", "incorporation of 10", "of 10 additional", "10 additional amino", "additional amino acids", "amino acids at", "acids at the", "at the c", "the c terminus", "c terminus of", "terminus of sil6r.a", "of sil6r.a second", "sil6r.a second mechanism", "second mechanism for", "mechanism for the", "for the generation", "the generation of", "generation of sil6r", "of sil6r is", "sil6r is the", "is the proteolytic", "the proteolytic cleavage", "proteolytic cleavage or", "cleavage or 'shedding'", "or 'shedding' of", "'shedding' of membrane", "of membrane bound", "membrane bound il", "bound il 6r.", "il 6r. two", "6r. two proteases", "two proteases adam10", "proteases adam10 and", "adam10 and adam17", "and adam17 are", "adam17 are thought", "are thought to", "thought to contribute", "to contribute to", "contribute to this", "this briso", "briso et al.", "et al. 2008", "al. 2008 .", "2008 . sil6r", ". sil6r can", "sil6r can bind", "can bind il6", "bind il6 and", "il6 and stimulate", "and stimulate cells", "stimulate cells that", "cells that express", "that express gp130", "express gp130 but", "gp130 but not", "but not il6r", "not il6r alpha", "alpha a", "a process that", "process that is", "that is termed", "is termed trans", "termed trans signaling.", "trans signaling. this", "signaling. this explains", "this explains why", "explains why many", "why many cells", "cells including", "including hematopoietic progenitor", "hematopoietic progenitor cells", "cells neuronal", "cells endothelial", "cells smooth", "smooth muscle cells", "cells and", "and embryonic stem", "embryonic stem cells", "cells do", "do not respond", "not respond to", "respond to il6", "to il6 alone", "alone but", "but show a", "show a remarkable", "a remarkable response", "remarkable response to", "response to il6/sil6r.", "to il6/sil6r. it", "il6/sil6r. it is", "it is clear", "is clear that", "clear that the", "that the trans", "the trans signaling", "trans signaling pathway", "signaling pathway is", "pathway is responsible", "is responsible for", "responsible for the", "for the pro", "the pro inflammatory", "pro inflammatory activities", "inflammatory activities of", "activities of il", "il 6 whereas", "6 whereas the", "whereas the membrane", "the membrane bound", "membrane bound receptor", "bound receptor governs", "receptor governs regenerative", "governs regenerative and", "regenerative and anti", "and anti inflammatory", "anti inflammatory il", "inflammatory il 6", "il 6 activities

il6r", "6 activities

il6r signal", "activities

il6r signal transduction", "signal transduction is", "transduction is mediated", "is mediated by", "mediated by two", "by two pathways:the", "two pathways:the jak", "pathways:the jak stat", "stat janus", "janus family tyrosine", "family tyrosine kinase", "tyrosine kinase signal", "kinase signal transducer", "signal transducer and", "transducer and activator", "and activator of", "activator of transcription", "transcription pathway", "pathway and the", "and the ras", "the ras mapk", "mapk mitogen", "mitogen activated protein", "activated protein kinase", "kinase pathway.", "pathway. negative regulators", "negative regulators of", "regulators of il", "il 6 signaling", "6 signaling include", "signaling include socs", "socs suppressor", "suppressor of cytokine", "of cytokine signals", "signals and", "and shp2. within", "shp2. within the", "within the last", "the last few", "last few years", "few years different", "years different antibodies", "different antibodies have", "antibodies have been", "have been developed", "been developed to", "developed to inhibit", "to inhibit il", "inhibit il 6", "il 6 activity", "activity and", "and the first", "the first such", "first such antibodies", "such antibodies have", "have been introduced", "been introduced into", "introduced into the", "into the clinic", "the clinic for", "clinic for the", "for the treatment", "the treatment of", "treatment of inflammatory", "of inflammatory diseases", "diseases kopf", "kopf et al.", "et al. 2010", "al. 2010 .", "interleukin 6 il", "6 il 6", "il 6 is", "6 is a", "is a pleiotropic cytokine", "a pleiotropic cytokine with", "pleiotropic cytokine with roles", "cytokine with roles in", "with roles in processes", "roles in processes including", "in processes including immune", "processes including immune regulation", "immune regulation hematopoiesis", "oncogenesis metabolic control", "metabolic control and sleep.", "and sleep. it", "sleep. it is", "it is the founding", "is the founding member", "the founding member of", "founding member of a", "member of a family", "of a family of", "a family of il", "family of il 6", "of il 6 related", "il 6 related cytokines", "6 related cytokines such", "related cytokines such as", "cytokines such as il", "such as il 11", "il 11 il", "11 il 27", "il 27 leukemia inhibitory", "27 leukemia inhibitory factor", "inhibitory factor lif", "lif cilliary", "neurotrophic factor cntf", "cntf and oncostatin", "and oncostatin m.

the", "oncostatin m.

the il", "m.

the il 6", "

the il 6 receptor", "6 receptor il6r", "il6r consists of", "consists of an alpha", "of an alpha subunit", "an alpha subunit that", "alpha subunit that specifically", "subunit that specifically binds", "that specifically binds il", "specifically binds il 6", "binds il 6 and", "il 6 and a", "6 and a beta", "and a beta subunit", "beta subunit il6rb", "subunit il6rb or", "or gp130 which", "gp130 which is", "which is the signaling", "is the signaling component", "the signaling component of", "signaling component of all", "component of all the", "of all the receptors", "all the receptors for", "the receptors for cytokines", "receptors for cytokines related", "for cytokines related to", "cytokines related to il", "related to il 6.", "to il 6. il6r", "il 6. il6r alpha", "6. il6r alpha exists", "il6r alpha exists in", "alpha exists in transmembrane", "exists in transmembrane and", "in transmembrane and soluble", "transmembrane and soluble forms.", "and soluble forms. the", "soluble forms. the transmembrane", "forms. the transmembrane form", "the transmembrane form is", "transmembrane form is mainly", "form is mainly expressed", "is mainly expressed by", "mainly expressed by hepatocytes", "by hepatocytes neutrophils", "monocytes/macrophages and some", "and some lymphocytes. soluble", "some lymphocytes. soluble forms", "lymphocytes. soluble forms of", "soluble forms of il6r", "of il6r sil6r", "sil6r are also", "are also expressed by", "also expressed by these", "expressed by these cells.", "by these cells. two", "these cells. two major", "cells. two major mechanisms", "two major mechanisms for", "major mechanisms for the", "mechanisms for the production", "for the production of", "the production of sil6r", "production of sil6r have", "of sil6r have been", "sil6r have been proposed.", "have been proposed. alternative", "been proposed. alternative splicing", "proposed. alternative splicing generates", "alternative splicing generates a", "splicing generates a transcript", "generates a transcript lacking", "a transcript lacking the", "transcript lacking the transmembrane", "lacking the transmembrane domain", "the transmembrane domain by", "transmembrane domain by using", "domain by using splicing", "by using splicing donor", "using splicing donor and", "splicing donor and acceptor", "donor and acceptor sites", "and acceptor sites that", "acceptor sites that flank", "sites that flank the", "that flank the transmembrane", "flank the transmembrane domain", "the transmembrane domain coding", "transmembrane domain coding region.", "domain coding region. this", "coding region. this also", "region. this also introduces", "this also introduces a", "also introduces a frameshift", "introduces a frameshift leading", "a frameshift leading to", "frameshift leading to the", "leading to the incorporation", "to the incorporation of", "the incorporation of 10", "incorporation of 10 additional", "of 10 additional amino", "10 additional amino acids", "additional amino acids at", "amino acids at the", "acids at the c", "at the c terminus", "the c terminus of", "c terminus of sil6r.a", "terminus of sil6r.a second", "of sil6r.a second mechanism", "sil6r.a second mechanism for", "second mechanism for the", "mechanism for the generation", "for the generation of", "the generation of sil6r", "generation of sil6r is", "of sil6r is the", "sil6r is the proteolytic", "is the proteolytic cleavage", "the proteolytic cleavage or", "proteolytic cleavage or 'shedding'", "cleavage or 'shedding' of", "or 'shedding' of membrane", "'shedding' of membrane bound", "of membrane bound il", "membrane bound il 6r.", "bound il 6r. two", "il 6r. two proteases", "6r. two proteases adam10", "two proteases adam10 and", "proteases adam10 and adam17", "adam10 and adam17 are", "and adam17 are thought", "adam17 are thought to", "are thought to contribute", "thought to contribute to", "to contribute to this", "to this briso", "this briso et", "briso et al. 2008", "et al. 2008 .", "al. 2008 . sil6r", "2008 . sil6r can", ". sil6r can bind", "sil6r can bind il6", "can bind il6 and", "bind il6 and stimulate", "il6 and stimulate cells", "and stimulate cells that", "stimulate cells that express", "cells that express gp130", "that express gp130 but", "express gp130 but not", "gp130 but not il6r", "but not il6r alpha", "il6r alpha a", "alpha a process", "a process that is", "process that is termed", "that is termed trans", "is termed trans signaling.", "termed trans signaling. this", "trans signaling. this explains", "signaling. this explains why", "this explains why many", "explains why many cells", "many cells including", "cells including hematopoietic", "including hematopoietic progenitor cells", "progenitor cells neuronal", "cells neuronal cells", "neuronal cells endothelial", "cells endothelial cells", "endothelial cells smooth", "cells smooth muscle", "muscle cells and", "cells and embryonic", "and embryonic stem cells", "stem cells do", "cells do not", "do not respond to", "not respond to il6", "respond to il6 alone", "il6 alone but", "alone but show", "but show a remarkable", "show a remarkable response", "a remarkable response to", "remarkable response to il6/sil6r.", "response to il6/sil6r. it", "to il6/sil6r. it is", "il6/sil6r. it is clear", "it is clear that", "is clear that the", "clear that the trans", "that the trans signaling", "the trans signaling pathway", "trans signaling pathway is", "signaling pathway is responsible", "pathway is responsible for", "is responsible for the", "responsible for the pro", "for the pro inflammatory", "the pro inflammatory activities", "pro inflammatory activities of", "inflammatory activities of il", "activities of il 6", "of il 6 whereas", "il 6 whereas the", "6 whereas the membrane", "whereas the membrane bound", "the membrane bound receptor", "membrane bound receptor governs", "bound receptor governs regenerative", "receptor governs regenerative and", "governs regenerative and anti", "regenerative and anti inflammatory", "and anti inflammatory il", "anti inflammatory il 6", "inflammatory il 6 activities

il6r", "il 6 activities

il6r signal", "6 activities

il6r signal transduction", "activities

il6r signal transduction is", "signal transduction is mediated", "transduction is mediated by", "is mediated by two", "mediated by two pathways:the", "by two pathways:the jak", "two pathways:the jak stat", "jak stat janus", "stat janus family", "janus family tyrosine kinase", "family tyrosine kinase signal", "tyrosine kinase signal transducer", "kinase signal transducer and", "signal transducer and activator", "transducer and activator of", "and activator of transcription", "of transcription pathway", "transcription pathway and", "pathway and the ras", "and the ras mapk", "ras mapk mitogen", "mapk mitogen activated", "mitogen activated protein kinase", "protein kinase pathway.", "kinase pathway. negative", "pathway. negative regulators of", "negative regulators of il", "regulators of il 6", "of il 6 signaling", "il 6 signaling include", "6 signaling include socs", "include socs suppressor", "socs suppressor of", "suppressor of cytokine signals", "cytokine signals and", "signals and shp2.", "and shp2. within the", "shp2. within the last", "within the last few", "the last few years", "last few years different", "few years different antibodies", "years different antibodies have", "different antibodies have been", "antibodies have been developed", "have been developed to", "been developed to inhibit", "developed to inhibit il", "to inhibit il 6", "inhibit il 6 activity", "6 activity and", "activity and the", "and the first such", "the first such antibodies", "first such antibodies have", "such antibodies have been", "antibodies have been introduced", "have been introduced into", "been introduced into the", "introduced into the clinic", "into the clinic for", "the clinic for the", "clinic for the treatment", "for the treatment of", "the treatment of inflammatory", "treatment of inflammatory diseases", "inflammatory diseases kopf", "diseases kopf et", "kopf et al. 2010", "et al. 2010 .", "interleukin 6 il 6", "il 6 is a", "6 is a pleiotropic", "is a pleiotropic cytokine with", "a pleiotropic cytokine with roles", "pleiotropic cytokine with roles in", "cytokine with roles in processes", "with roles in processes including", "roles in processes including immune", "in processes including immune regulation", "including immune regulation hematopoiesis", "regulation hematopoiesis inflammation", "hematopoiesis inflammation oncogenesis", "inflammation oncogenesis metabolic", "oncogenesis metabolic control and", "control and sleep. it", "and sleep. it is", "sleep. it is the", "it is the founding member", "is the founding member of", "the founding member of a", "founding member of a family", "member of a family of", "of a family of il", "a family of il 6", "family of il 6 related", "of il 6 related cytokines", "il 6 related cytokines such", "6 related cytokines such as", "related cytokines such as il", "cytokines such as il 11", "as il 11 il", "il 11 il 27", "11 il 27 leukemia", "il 27 leukemia inhibitory factor", "leukemia inhibitory factor lif", "lif cilliary neurotrophic", "cilliary neurotrophic factor cntf", "factor cntf and", "cntf and oncostatin m.", "and oncostatin m.

the il", "oncostatin m.

the il 6", "m.

the il 6 receptor", "il 6 receptor il6r", "receptor il6r consists", "il6r consists of an", "consists of an alpha subunit", "of an alpha subunit that", "an alpha subunit that specifically", "alpha subunit that specifically binds", "subunit that specifically binds il", "that specifically binds il 6", "specifically binds il 6 and", "binds il 6 and a", "il 6 and a beta", "6 and a beta subunit", "a beta subunit il6rb", "beta subunit il6rb or", "subunit il6rb or gp130", "il6rb or gp130 which", "or gp130 which is", "gp130 which is the", "which is the signaling component", "is the signaling component of", "the signaling component of all", "signaling component of all the", "component of all the receptors", "of all the receptors for", "all the receptors for cytokines", "the receptors for cytokines related", "receptors for cytokines related to", "for cytokines related to il", "cytokines related to il 6.", "related to il 6. il6r", "to il 6. il6r alpha", "il 6. il6r alpha exists", "6. il6r alpha exists in", "il6r alpha exists in transmembrane", "alpha exists in transmembrane and", "exists in transmembrane and soluble", "in transmembrane and soluble forms.", "transmembrane and soluble forms. the", "and soluble forms. the transmembrane", "soluble forms. the transmembrane form", "forms. the transmembrane form is", "the transmembrane form is mainly", "transmembrane form is mainly expressed", "form is mainly expressed by", "is mainly expressed by hepatocytes", "expressed by hepatocytes neutrophils", "hepatocytes neutrophils monocytes/macrophages", "neutrophils monocytes/macrophages and", "monocytes/macrophages and some lymphocytes.", "and some lymphocytes. soluble forms", "some lymphocytes. soluble forms of", "lymphocytes. soluble forms of il6r", "forms of il6r sil6r", "il6r sil6r are", "sil6r are also expressed", "are also expressed by these", "also expressed by these cells.", "expressed by these cells. two", "by these cells. two major", "these cells. two major mechanisms", "cells. two major mechanisms for", "two major mechanisms for the", "major mechanisms for the production", "mechanisms for the production of", "for the production of sil6r", "the production of sil6r have", "production of sil6r have been", "of sil6r have been proposed.", "sil6r have been proposed. alternative", "have been proposed. alternative splicing", "been proposed. alternative splicing generates", "proposed. alternative splicing generates a", "alternative splicing generates a transcript", "splicing generates a transcript lacking", "generates a transcript lacking the", "a transcript lacking the transmembrane", "transcript lacking the transmembrane domain", "lacking the transmembrane domain by", "the transmembrane domain by using", "transmembrane domain by using splicing", "domain by using splicing donor", "by using splicing donor and", "using splicing donor and acceptor", "splicing donor and acceptor sites", "donor and acceptor sites that", "and acceptor sites that flank", "acceptor sites that flank the", "sites that flank the transmembrane", "that flank the transmembrane domain", "flank the transmembrane domain coding", "the transmembrane domain coding region.", "transmembrane domain coding region. this", "domain coding region. this also", "coding region. this also introduces", "region. this also introduces a", "this also introduces a frameshift", "also introduces a frameshift leading", "introduces a frameshift leading to", "a frameshift leading to the", "frameshift leading to the incorporation", "leading to the incorporation of", "to the incorporation of 10", "the incorporation of 10 additional", "incorporation of 10 additional amino", "of 10 additional amino acids", "10 additional amino acids at", "additional amino acids at the", "amino acids at the c", "acids at the c terminus", "at the c terminus of", "the c terminus of sil6r.a", "c terminus of sil6r.a second", "terminus of sil6r.a second mechanism", "of sil6r.a second mechanism for", "sil6r.a second mechanism for the", "second mechanism for the generation", "mechanism for the generation of", "for the generation of sil6r", "the generation of sil6r is", "generation of sil6r is the", "of sil6r is the proteolytic", "sil6r is the proteolytic cleavage", "is the proteolytic cleavage or", "the proteolytic cleavage or 'shedding'", "proteolytic cleavage or 'shedding' of", "cleavage or 'shedding' of membrane", "or 'shedding' of membrane bound", "'shedding' of membrane bound il", "of membrane bound il 6r.", "membrane bound il 6r. two", "bound il 6r. two proteases", "il 6r. two proteases adam10", "6r. two proteases adam10 and", "two proteases adam10 and adam17", "proteases adam10 and adam17 are", "adam10 and adam17 are thought", "and adam17 are thought to", "adam17 are thought to contribute", "are thought to contribute to", "thought to contribute to this", "contribute to this briso", "to this briso et", "this briso et al.", "briso et al. 2008 .", "et al. 2008 . sil6r", "al. 2008 . sil6r can", "2008 . sil6r can bind", ". sil6r can bind il6", "sil6r can bind il6 and", "can bind il6 and stimulate", "bind il6 and stimulate cells", "il6 and stimulate cells that", "and stimulate cells that express", "stimulate cells that express gp130", "cells that express gp130 but", "that express gp130 but not", "express gp130 but not il6r", "gp130 but not il6r alpha", "not il6r alpha a", "il6r alpha a process", "alpha a process that", "a process that is termed", "process that is termed trans", "that is termed trans signaling.", "is termed trans signaling. this", "termed trans signaling. this explains", "trans signaling. this explains why", "signaling. this explains why many", "this explains why many cells", "why many cells including", "many cells including hematopoietic", "cells including hematopoietic progenitor", "hematopoietic progenitor cells neuronal", "progenitor cells neuronal cells", "neuronal cells endothelial cells", "endothelial cells smooth muscle", "cells smooth muscle cells", "smooth muscle cells and", "muscle cells and embryonic", "cells and embryonic stem", "embryonic stem cells do", "stem cells do not", "cells do not respond", "do not respond to il6", "not respond to il6 alone", "to il6 alone but", "il6 alone but show", "alone but show a", "but show a remarkable response", "show a remarkable response to", "a remarkable response to il6/sil6r.", "remarkable response to il6/sil6r. it", "response to il6/sil6r. it is", "to il6/sil6r. it is clear", "il6/sil6r. it is clear that", "it is clear that the", "is clear that the trans", "clear that the trans signaling", "that the trans signaling pathway", "the trans signaling pathway is", "trans signaling pathway is responsible", "signaling pathway is responsible for", "pathway is responsible for the", "is responsible for the pro", "responsible for the pro inflammatory", "for the pro inflammatory activities", "the pro inflammatory activities of", "pro inflammatory activities of il", "inflammatory activities of il 6", "activities of il 6 whereas", "of il 6 whereas the", "il 6 whereas the membrane", "6 whereas the membrane bound", "whereas the membrane bound receptor", "the membrane bound receptor governs", "membrane bound receptor governs regenerative", "bound receptor governs regenerative and", "receptor governs regenerative and anti", "governs regenerative and anti inflammatory", "regenerative and anti inflammatory il", "and anti inflammatory il 6", "anti inflammatory il 6 activities

il6r", "inflammatory il 6 activities

il6r signal", "il 6 activities

il6r signal transduction", "6 activities

il6r signal transduction is", "activities

il6r signal transduction is mediated", "signal transduction is mediated by", "transduction is mediated by two", "is mediated by two pathways:the", "mediated by two pathways:the jak", "by two pathways:the jak stat", "pathways:the jak stat janus", "jak stat janus family", "stat janus family tyrosine", "janus family tyrosine kinase signal", "family tyrosine kinase signal transducer", "tyrosine kinase signal transducer and", "kinase signal transducer and activator", "signal transducer and activator of", "transducer and activator of transcription", "activator of transcription pathway", "of transcription pathway and", "transcription pathway and the", "pathway and the ras mapk", "the ras mapk mitogen", "ras mapk mitogen activated", "mapk mitogen activated protein", "activated protein kinase pathway.", "protein kinase pathway. negative", "kinase pathway. negative regulators", "pathway. negative regulators of il", "negative regulators of il 6", "regulators of il 6 signaling", "of il 6 signaling include", "il 6 signaling include socs", "signaling include socs suppressor", "include socs suppressor of", "socs suppressor of cytokine", "of cytokine signals and", "cytokine signals and shp2.", "signals and shp2. within", "and shp2. within the last", "shp2. within the last few", "within the last few years", "the last few years different", "last few years different antibodies", "few years different antibodies have", "years different antibodies have been", "different antibodies have been developed", "antibodies have been developed to", "have been developed to inhibit", "been developed to inhibit il", "developed to inhibit il 6", "to inhibit il 6 activity", "il 6 activity and", "6 activity and the", "activity and the first", "and the first such antibodies", "the first such antibodies have", "first such antibodies have been", "such antibodies have been introduced", "antibodies have been introduced into", "have been introduced into the", "been introduced into the clinic", "introduced into the clinic for", "into the clinic for the", "the clinic for the treatment", "clinic for the treatment of", "for the treatment of inflammatory", "the treatment of inflammatory diseases", "of inflammatory diseases kopf", "inflammatory diseases kopf et", "diseases kopf et al.", "kopf et al. 2010 ." ] }, { "record_id": "GLY_000594_1_8", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "109704", "r hsa", "hsa 109704", "r hsa 109704" ] }, { "record_id": "GLY_000594_1_8", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi3k cascade", "the pi3k", "phosphatidlyinositol 3", "3 kinase", "akt signaling", "signaling pathway", "pathway stimulates", "stimulates cell", "cell growth", "growth and", "and survival.", "pi3k phosphatidlyinositol", "phosphatidlyinositol 3 kinase", "akt signaling pathway", "signaling pathway stimulates", "pathway stimulates cell", "stimulates cell growth", "cell growth and", "growth and survival.", "the pi3k phosphatidlyinositol", "pi3k phosphatidlyinositol 3", "akt signaling pathway stimulates", "signaling pathway stimulates cell", "pathway stimulates cell growth", "stimulates cell growth and", "cell growth and survival.", "the pi3k phosphatidlyinositol 3", "pi3k phosphatidlyinositol 3 kinase", "kinase akt", "akt signaling pathway stimulates cell", "signaling pathway stimulates cell growth", "pathway stimulates cell growth and", "stimulates cell growth and survival." ] }, { "record_id": "GLY_000594_1_9", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111458", "r hsa", "hsa 111458", "r hsa 111458" ] }, { "record_id": "GLY_000594_1_9", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of apoptosome", "formation of apoptosome", "the apoptosome", "apoptosome is", "is a", "a cytoplasmic", "cytoplasmic protein", "protein complex", "complex of", "of two", "two major", "major components", "components \u2011", "\u2011 the", "the adapter", "adapter protein", "protein apoptotic", "apoptotic protease", "protease activating", "activating factor", "factor 1", "and the", "the protease", "protease caspase\u20119", "which interact", "interact with", "with each", "each other", "other through", "through their", "their caspase", "caspase recruitment", "recruitment domains", "qin et", "et al.", "al. 1999", "yuan s", "s et", "al. 2010", "s &", "& akey", "akey cw", "cw 2013", "2013 .", ". the", "the function", "function of", "of the", "is to", "to assemble", "assemble a", "a multimeric", "multimeric complex", "complex between", "between apaf1", "apaf1 and", "and procaspase", "procaspase 9", "9 cards", "cards to", "to facilitate", "facilitate casp9", "casp9 activation", "jiang x", "x and", "and wang", "wang x", "x 2000", "srinivasrula sm", "sm et", "al. 2001", "shiozaki en", "en et", "al. 2002", "2002 .", "is assembled", "assembled upon", "upon apaf1", "apaf1 interaction", "interaction with", "with cytochrome", "cytochrome c", "which is", "is released", "released from", "from the", "the mitochondrial", "mitochondrial intermembrane", "intermembrane space", "space during", "during apoptosis", "zou h", "h et", "al. 1997", "al. 2013", "shakeri r", "r et", "al. 2017", "2017 .", ". cycs\u2011bound", "cycs\u2011bound apaf1", "apaf1 undergoes", "undergoes atp", "atp mediated", "mediated conformational", "conformational changes", "changes and", "and in", "in the", "the presence", "presence of", "of card", "card of", "of casp9", "casp9 oligomerizes", "oligomerizes into", "into a", "a heptameric", "heptameric complex", "which activates", "activates procaspase", "bratton sb", "sb et", "acehan d", "d et", "yu x", "x et", "al. 2005", "su tw", "tw et", ". in", "recruitment of", "of caspase", "caspase 9", "9 may", "may occur", "occur before", "before oligomerization", "oligomerization in", "the card", "card disk", "which presumably", "presumably brings", "brings the", "the caspase", "caspase domain", "domain into", "into proximity", "proximity for", "for their", "their dimerization", "dimerization and", "and activation", "hu q", "q et", "al. 2014", "cheng tc", "tc et", "al. 2016", "2016 .", ". once", "once activated", "casp9 activates", "activates downstream", "downstream effector", "effector caspases\u20113", "caspases\u20113 and", "and \u20117.", "\u20117. the", "the activated", "activated effector", "effector caspases", "caspases then", "then cleave", "cleave various", "various cellular", "cellular proteins.

", "proteins.

different", "different models", "models have", "have been", "been proposed", "proposed to", "to explain", "explain casp9", "casp9 activation:", "activation: the", "the \u201cproximity\u2011driven", "\u201cproximity\u2011driven dimerization", "dimerization model\u201d", "model\u201d and", "the \u201cinduced", "\u201cinduced conformation", "conformation model\u201d.", "model\u201d. the", "the first", "first models", "models states", "states that", "that upon", "upon binding", "binding to", "to heptameric", "heptameric apaf1", "monomers of", "of procaspase\u20119", "procaspase\u20119 are", "are brought", "brought into", "into close", "close proximity", "proximity at", "at a", "a high", "high concentration", "acehan et", "renatus et", "2001 .", ". this", "this induces", "induces dimerization", "dimerization which", "is sufficient", "sufficient for", "for casp9", "activation whereas", "whereas autoprocessing", "autoprocessing within", "within the", "apoptosome complex", "complex merely", "merely stabilizes", "stabilizes casp9", "casp9 dimer", "boatright km", "km et", "al. 2003", "pop c", "c et", "al. 2006", "2006 .", "conformation model\u201d", "model\u201d is", "is based", "based on", "on the", "the observation", "observation that", "that casp9", "casp9 has", "has a", "a much", "much higher", "higher level", "level of", "of catalytic", "catalytic activity", "activity when", "when it's", "it's bound", "bound to", "to the", "the apoptosome.", "apoptosome. the", "the model", "model suggests", "suggests that", "that a", "a conformational", "conformational change", "change occurs", "occurs at", "at the", "the active", "active site", "site of", "casp9 upon", "to apaf1", "apaf1 thus", "thus inducing", "inducing casp9", "casp9 homodimerization", "homodimerization and", "and stabilizing", "stabilizing it", "it in", "the catalytically", "catalytically active", "active conformation", ". casp9", "activation may", "may also", "also involve", "involve formation", "of a", "multimeric card:card", "card:card assembly", "assembly between", "and procaspase\u20119", "2014 .
", "the apoptosome is", "apoptosome is a", "is a cytoplasmic", "a cytoplasmic protein", "cytoplasmic protein complex", "protein complex of", "complex of two", "of two major", "two major components", "major components \u2011", "components \u2011 the", "\u2011 the adapter", "the adapter protein", "adapter protein apoptotic", "protein apoptotic protease", "apoptotic protease activating", "protease activating factor", "activating factor 1", "1 apaf1", "and the protease", "the protease caspase\u20119", "caspase\u20119 casp9", "casp9 which", "which interact with", "interact with each", "with each other", "each other through", "other through their", "through their caspase", "their caspase recruitment", "caspase recruitment domains", "domains card", "qin et al.", "et al. 1999", "1999 yuan", "yuan s et", "s et al.", "et al. 2010", "2010 yuan", "yuan s &", "s & akey", "& akey cw", "akey cw 2013", "cw 2013 .", "2013 . the", ". the function", "the function of", "function of the", "of the apoptosome", "apoptosome is to", "is to assemble", "to assemble a", "assemble a multimeric", "a multimeric complex", "multimeric complex between", "complex between apaf1", "between apaf1 and", "apaf1 and procaspase", "and procaspase 9", "procaspase 9 cards", "9 cards to", "cards to facilitate", "to facilitate casp9", "facilitate casp9 activation", "activation jiang", "jiang x and", "x and wang", "and wang x", "wang x 2000", "2000 srinivasrula", "srinivasrula sm et", "sm et al.", "et al. 2001", "2001 shiozaki", "shiozaki en et", "en et al.", "et al. 2002", "al. 2002 .", "2002 . the", ". the apoptosome", "apoptosome is assembled", "is assembled upon", "assembled upon apaf1", "upon apaf1 interaction", "apaf1 interaction with", "interaction with cytochrome", "with cytochrome c", "c cycs", "which is released", "is released from", "released from the", "from the mitochondrial", "the mitochondrial intermembrane", "mitochondrial intermembrane space", "intermembrane space during", "space during apoptosis", "apoptosis zou", "zou h et", "h et al.", "et al. 1997", "1997 yuan", "et al. 2013", "2013 shakeri", "shakeri r et", "r et al.", "et al. 2017", "al. 2017 .", "2017 . cycs\u2011bound", ". cycs\u2011bound apaf1", "cycs\u2011bound apaf1 undergoes", "apaf1 undergoes atp", "undergoes atp mediated", "atp mediated conformational", "mediated conformational changes", "conformational changes and", "changes and in", "and in the", "in the presence", "the presence of", "presence of card", "of card of", "card of casp9", "of casp9 oligomerizes", "casp9 oligomerizes into", "oligomerizes into a", "into a heptameric", "a heptameric complex", "complex which", "which activates procaspase", "activates procaspase 9", "9 zou", "1997 bratton", "bratton sb et", "sb et al.", "2010 acehan", "acehan d et", "d et al.", "2002 yu", "yu x et", "x et al.", "et al. 2005", "2005 yuan", "2010 su", "su tw et", "tw et al.", "2017 . in", ". in the", "in the apoptosome", "apoptosome recruitment", "recruitment of caspase", "of caspase 9", "caspase 9 may", "9 may occur", "may occur before", "occur before oligomerization", "before oligomerization in", "oligomerization in the", "in the card", "the card disk", "disk which", "which presumably brings", "presumably brings the", "brings the caspase", "the caspase domain", "caspase domain into", "domain into proximity", "into proximity for", "proximity for their", "for their dimerization", "their dimerization and", "dimerization and activation", "activation su", "2017 hu", "hu q et", "q et al.", "et al. 2014", "2014 cheng", "cheng tc et", "tc et al.", "et al. 2016", "al. 2016 .", "2016 . once", ". once activated", "activated casp9", "casp9 activates downstream", "activates downstream effector", "downstream effector caspases\u20113", "effector caspases\u20113 and", "caspases\u20113 and \u20117.", "and \u20117. the", "\u20117. the activated", "the activated effector", "activated effector caspases", "effector caspases then", "caspases then cleave", "then cleave various", "cleave various cellular", "various cellular proteins.

", "cellular proteins.

different", "proteins.

different models", "different models have", "models have been", "have been proposed", "been proposed to", "proposed to explain", "to explain casp9", "explain casp9 activation:", "casp9 activation: the", "activation: the \u201cproximity\u2011driven", "the \u201cproximity\u2011driven dimerization", "\u201cproximity\u2011driven dimerization model\u201d", "dimerization model\u201d and", "model\u201d and the", "and the \u201cinduced", "the \u201cinduced conformation", "\u201cinduced conformation model\u201d.", "conformation model\u201d. the", "model\u201d. the first", "the first models", "first models states", "models states that", "states that upon", "that upon binding", "upon binding to", "binding to heptameric", "to heptameric apaf1", "apaf1 monomers", "monomers of procaspase\u20119", "of procaspase\u20119 are", "procaspase\u20119 are brought", "are brought into", "brought into close", "into close proximity", "close proximity at", "proximity at a", "at a high", "a high concentration", "concentration acehan", "acehan et al.", "2002 renatus", "renatus et al.", "al. 2001 .", "2001 . this", ". this induces", "this induces dimerization", "induces dimerization which", "dimerization which is", "which is sufficient", "is sufficient for", "sufficient for casp9", "for casp9 activation", "casp9 activation whereas", "activation whereas autoprocessing", "whereas autoprocessing within", "autoprocessing within the", "within the apoptosome", "the apoptosome complex", "apoptosome complex merely", "complex merely stabilizes", "merely stabilizes casp9", "stabilizes casp9 dimer", "dimer boatright", "boatright km et", "km et al.", "et al. 2003", "2003 pop", "pop c et", "c et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the \u201cinduced", "\u201cinduced conformation model\u201d", "conformation model\u201d is", "model\u201d is based", "is based on", "based on the", "on the observation", "the observation that", "observation that casp9", "that casp9 has", "casp9 has a", "has a much", "a much higher", "much higher level", "higher level of", "level of catalytic", "of catalytic activity", "catalytic activity when", "activity when it's", "when it's bound", "it's bound to", "bound to the", "to the apoptosome.", "the apoptosome. the", "apoptosome. the model", "the model suggests", "model suggests that", "suggests that a", "that a conformational", "a conformational change", "conformational change occurs", "change occurs at", "occurs at the", "at the active", "the active site", "active site of", "site of casp9", "of casp9 upon", "casp9 upon binding", "binding to apaf1", "to apaf1 thus", "apaf1 thus inducing", "thus inducing casp9", "inducing casp9 homodimerization", "casp9 homodimerization and", "homodimerization and stabilizing", "and stabilizing it", "stabilizing it in", "it in the", "in the catalytically", "the catalytically active", "catalytically active conformation", "conformation shiozaki", "2002 . casp9", ". casp9 activation", "casp9 activation may", "activation may also", "may also involve", "also involve formation", "involve formation of", "formation of a", "of a multimeric", "a multimeric card:card", "multimeric card:card assembly", "card:card assembly between", "assembly between apaf1", "apaf1 and procaspase\u20119", "procaspase\u20119 hu", "al. 2014 .
", "the apoptosome is a", "apoptosome is a cytoplasmic", "is a cytoplasmic protein", "a cytoplasmic protein complex", "cytoplasmic protein complex of", "protein complex of two", "complex of two major", "of two major components", "two major components \u2011", "major components \u2011 the", "components \u2011 the adapter", "\u2011 the adapter protein", "the adapter protein apoptotic", "adapter protein apoptotic protease", "protein apoptotic protease activating", "apoptotic protease activating factor", "protease activating factor 1", "factor 1 apaf1", "apaf1 and the", "and the protease caspase\u20119", "protease caspase\u20119 casp9", "casp9 which interact", "which interact with each", "interact with each other", "with each other through", "each other through their", "other through their caspase", "through their caspase recruitment", "their caspase recruitment domains", "recruitment domains card", "card qin", "qin et al. 1999", "al. 1999 yuan", "1999 yuan s", "yuan s et al.", "s et al. 2010", "al. 2010 yuan", "2010 yuan s", "yuan s & akey", "s & akey cw", "& akey cw 2013", "akey cw 2013 .", "cw 2013 . the", "2013 . the function", ". the function of", "the function of the", "function of the apoptosome", "of the apoptosome is", "the apoptosome is to", "apoptosome is to assemble", "is to assemble a", "to assemble a multimeric", "assemble a multimeric complex", "a multimeric complex between", "multimeric complex between apaf1", "complex between apaf1 and", "between apaf1 and procaspase", "apaf1 and procaspase 9", "and procaspase 9 cards", "procaspase 9 cards to", "9 cards to facilitate", "cards to facilitate casp9", "to facilitate casp9 activation", "casp9 activation jiang", "activation jiang x", "jiang x and wang", "x and wang x", "and wang x 2000", "x 2000 srinivasrula", "2000 srinivasrula sm", "srinivasrula sm et al.", "sm et al. 2001", "al. 2001 shiozaki", "2001 shiozaki en", "shiozaki en et al.", "en et al. 2002", "et al. 2002 .", "al. 2002 . the", "2002 . the apoptosome", ". the apoptosome is", "the apoptosome is assembled", "apoptosome is assembled upon", "is assembled upon apaf1", "assembled upon apaf1 interaction", "upon apaf1 interaction with", "apaf1 interaction with cytochrome", "interaction with cytochrome c", "cytochrome c cycs", "cycs which", "which is released from", "is released from the", "released from the mitochondrial", "from the mitochondrial intermembrane", "the mitochondrial intermembrane space", "mitochondrial intermembrane space during", "intermembrane space during apoptosis", "during apoptosis zou", "apoptosis zou h", "zou h et al.", "h et al. 1997", "al. 1997 yuan", "1997 yuan s", "s et al. 2013", "al. 2013 shakeri", "2013 shakeri r", "shakeri r et al.", "r et al. 2017", "et al. 2017 .", "al. 2017 . cycs\u2011bound", "2017 . cycs\u2011bound apaf1", ". cycs\u2011bound apaf1 undergoes", "cycs\u2011bound apaf1 undergoes atp", "apaf1 undergoes atp mediated", "undergoes atp mediated conformational", "atp mediated conformational changes", "mediated conformational changes and", "conformational changes and in", "changes and in the", "and in the presence", "in the presence of", "the presence of card", "presence of card of", "of card of casp9", "card of casp9 oligomerizes", "of casp9 oligomerizes into", "casp9 oligomerizes into a", "oligomerizes into a heptameric", "into a heptameric complex", "heptameric complex which", "complex which activates", "which activates procaspase 9", "procaspase 9 zou", "9 zou h", "al. 1997 bratton", "1997 bratton sb", "bratton sb et al.", "sb et al. 2010", "al. 2010 acehan", "2010 acehan d", "acehan d et al.", "d et al. 2002", "al. 2002 yu", "2002 yu x", "yu x et al.", "x et al. 2005", "al. 2005 yuan", "2005 yuan s", "al. 2010 su", "2010 su tw", "su tw et al.", "tw et al. 2017", "al. 2017 . in", "2017 . in the", ". in the apoptosome", "the apoptosome recruitment", "apoptosome recruitment of", "recruitment of caspase 9", "of caspase 9 may", "caspase 9 may occur", "9 may occur before", "may occur before oligomerization", "occur before oligomerization in", "before oligomerization in the", "oligomerization in the card", "in the card disk", "card disk which", "disk which presumably", "which presumably brings the", "presumably brings the caspase", "brings the caspase domain", "the caspase domain into", "caspase domain into proximity", "domain into proximity for", "into proximity for their", "proximity for their dimerization", "for their dimerization and", "their dimerization and activation", "and activation su", "activation su tw", "al. 2017 hu", "2017 hu q", "hu q et al.", "q et al. 2014", "al. 2014 cheng", "2014 cheng tc", "cheng tc et al.", "tc et al. 2016", "et al. 2016 .", "al. 2016 . once", "2016 . once activated", "once activated casp9", "activated casp9 activates", "casp9 activates downstream effector", "activates downstream effector caspases\u20113", "downstream effector caspases\u20113 and", "effector caspases\u20113 and \u20117.", "caspases\u20113 and \u20117. the", "and \u20117. the activated", "\u20117. the activated effector", "the activated effector caspases", "activated effector caspases then", "effector caspases then cleave", "caspases then cleave various", "then cleave various cellular", "cleave various cellular proteins.

", "various cellular proteins.

different", "cellular proteins.

different models", "proteins.

different models have", "different models have been", "models have been proposed", "have been proposed to", "been proposed to explain", "proposed to explain casp9", "to explain casp9 activation:", "explain casp9 activation: the", "casp9 activation: the \u201cproximity\u2011driven", "activation: the \u201cproximity\u2011driven dimerization", "the \u201cproximity\u2011driven dimerization model\u201d", "\u201cproximity\u2011driven dimerization model\u201d and", "dimerization model\u201d and the", "model\u201d and the \u201cinduced", "and the \u201cinduced conformation", "the \u201cinduced conformation model\u201d.", "\u201cinduced conformation model\u201d. the", "conformation model\u201d. the first", "model\u201d. the first models", "the first models states", "first models states that", "models states that upon", "states that upon binding", "that upon binding to", "upon binding to heptameric", "binding to heptameric apaf1", "heptameric apaf1 monomers", "apaf1 monomers of", "monomers of procaspase\u20119 are", "of procaspase\u20119 are brought", "procaspase\u20119 are brought into", "are brought into close", "brought into close proximity", "into close proximity at", "close proximity at a", "proximity at a high", "at a high concentration", "high concentration acehan", "concentration acehan et", "acehan et al. 2002", "al. 2002 renatus", "2002 renatus et", "renatus et al. 2001", "et al. 2001 .", "al. 2001 . this", "2001 . this induces", ". this induces dimerization", "this induces dimerization which", "induces dimerization which is", "dimerization which is sufficient", "which is sufficient for", "is sufficient for casp9", "sufficient for casp9 activation", "for casp9 activation whereas", "casp9 activation whereas autoprocessing", "activation whereas autoprocessing within", "whereas autoprocessing within the", "autoprocessing within the apoptosome", "within the apoptosome complex", "the apoptosome complex merely", "apoptosome complex merely stabilizes", "complex merely stabilizes casp9", "merely stabilizes casp9 dimer", "casp9 dimer boatright", "dimer boatright km", "boatright km et al.", "km et al. 2003", "al. 2003 pop", "2003 pop c", "pop c et al.", "c et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the \u201cinduced", ". the \u201cinduced conformation", "the \u201cinduced conformation model\u201d", "\u201cinduced conformation model\u201d is", "conformation model\u201d is based", "model\u201d is based on", "is based on the", "based on the observation", "on the observation that", "the observation that casp9", "observation that casp9 has", "that casp9 has a", "casp9 has a much", "has a much higher", "a much higher level", "much higher level of", "higher level of catalytic", "level of catalytic activity", "of catalytic activity when", "catalytic activity when it's", "activity when it's bound", "when it's bound to", "it's bound to the", "bound to the apoptosome.", "to the apoptosome. the", "the apoptosome. the model", "apoptosome. the model suggests", "the model suggests that", "model suggests that a", "suggests that a conformational", "that a conformational change", "a conformational change occurs", "conformational change occurs at", "change occurs at the", "occurs at the active", "at the active site", "the active site of", "active site of casp9", "site of casp9 upon", "of casp9 upon binding", "casp9 upon binding to", "upon binding to apaf1", "binding to apaf1 thus", "to apaf1 thus inducing", "apaf1 thus inducing casp9", "thus inducing casp9 homodimerization", "inducing casp9 homodimerization and", "casp9 homodimerization and stabilizing", "homodimerization and stabilizing it", "and stabilizing it in", "stabilizing it in the", "it in the catalytically", "in the catalytically active", "the catalytically active conformation", "active conformation shiozaki", "conformation shiozaki en", "al. 2002 . casp9", "2002 . casp9 activation", ". casp9 activation may", "casp9 activation may also", "activation may also involve", "may also involve formation", "also involve formation of", "involve formation of a", "formation of a multimeric", "of a multimeric card:card", "a multimeric card:card assembly", "multimeric card:card assembly between", "card:card assembly between apaf1", "assembly between apaf1 and", "between apaf1 and procaspase\u20119", "and procaspase\u20119 hu", "procaspase\u20119 hu q", "et al. 2014 .
", "the apoptosome is a cytoplasmic", "apoptosome is a cytoplasmic protein", "is a cytoplasmic protein complex", "a cytoplasmic protein complex of", "cytoplasmic protein complex of two", "protein complex of two major", "complex of two major components", "of two major components \u2011", "two major components \u2011 the", "major components \u2011 the adapter", "components \u2011 the adapter protein", "\u2011 the adapter protein apoptotic", "the adapter protein apoptotic protease", "adapter protein apoptotic protease activating", "protein apoptotic protease activating factor", "apoptotic protease activating factor 1", "activating factor 1 apaf1", "1 apaf1 and", "apaf1 and the protease", "the protease caspase\u20119 casp9", "caspase\u20119 casp9 which", "casp9 which interact with", "which interact with each other", "interact with each other through", "with each other through their", "each other through their caspase", "other through their caspase recruitment", "through their caspase recruitment domains", "caspase recruitment domains card", "card qin et", "et al. 1999 yuan", "al. 1999 yuan s", "1999 yuan s et", "yuan s et al. 2010", "et al. 2010 yuan", "al. 2010 yuan s", "2010 yuan s &", "yuan s & akey cw", "s & akey cw 2013", "& akey cw 2013 .", "akey cw 2013 . the", "cw 2013 . the function", "2013 . the function of", ". the function of the", "the function of the apoptosome", "function of the apoptosome is", "of the apoptosome is to", "the apoptosome is to assemble", "apoptosome is to assemble a", "is to assemble a multimeric", "to assemble a multimeric complex", "assemble a multimeric complex between", "a multimeric complex between apaf1", "multimeric complex between apaf1 and", "complex between apaf1 and procaspase", "between apaf1 and procaspase 9", "apaf1 and procaspase 9 cards", "and procaspase 9 cards to", "procaspase 9 cards to facilitate", "9 cards to facilitate casp9", "cards to facilitate casp9 activation", "facilitate casp9 activation jiang", "casp9 activation jiang x", "activation jiang x and", "jiang x and wang x", "x and wang x 2000", "wang x 2000 srinivasrula", "x 2000 srinivasrula sm", "2000 srinivasrula sm et", "srinivasrula sm et al. 2001", "et al. 2001 shiozaki", "al. 2001 shiozaki en", "2001 shiozaki en et", "shiozaki en et al. 2002", "en et al. 2002 .", "et al. 2002 . the", "al. 2002 . the apoptosome", "2002 . the apoptosome is", ". the apoptosome is assembled", "the apoptosome is assembled upon", "apoptosome is assembled upon apaf1", "is assembled upon apaf1 interaction", "assembled upon apaf1 interaction with", "upon apaf1 interaction with cytochrome", "apaf1 interaction with cytochrome c", "with cytochrome c cycs", "cycs which is", "which is released from the", "is released from the mitochondrial", "released from the mitochondrial intermembrane", "from the mitochondrial intermembrane space", "the mitochondrial intermembrane space during", "mitochondrial intermembrane space during apoptosis", "space during apoptosis zou", "during apoptosis zou h", "apoptosis zou h et", "zou h et al. 1997", "et al. 1997 yuan", "al. 1997 yuan s", "1997 yuan s et", "yuan s et al. 2013", "et al. 2013 shakeri", "al. 2013 shakeri r", "2013 shakeri r et", "shakeri r et al. 2017", "r et al. 2017 .", "et al. 2017 . cycs\u2011bound", "al. 2017 . cycs\u2011bound apaf1", "2017 . cycs\u2011bound apaf1 undergoes", ". cycs\u2011bound apaf1 undergoes atp", "cycs\u2011bound apaf1 undergoes atp mediated", "apaf1 undergoes atp mediated conformational", "undergoes atp mediated conformational changes", "atp mediated conformational changes and", "mediated conformational changes and in", "conformational changes and in the", "changes and in the presence", "and in the presence of", "in the presence of card", "the presence of card of", "presence of card of casp9", "of card of casp9 oligomerizes", "card of casp9 oligomerizes into", "of casp9 oligomerizes into a", "casp9 oligomerizes into a heptameric", "oligomerizes into a heptameric complex", "a heptameric complex which", "heptameric complex which activates", "complex which activates procaspase", "activates procaspase 9 zou", "procaspase 9 zou h", "9 zou h et", "et al. 1997 bratton", "al. 1997 bratton sb", "1997 bratton sb et", "bratton sb et al. 2010", "et al. 2010 acehan", "al. 2010 acehan d", "2010 acehan d et", "acehan d et al. 2002", "et al. 2002 yu", "al. 2002 yu x", "2002 yu x et", "yu x et al. 2005", "et al. 2005 yuan", "al. 2005 yuan s", "2005 yuan s et", "et al. 2010 su", "al. 2010 su tw", "2010 su tw et", "su tw et al. 2017", "tw et al. 2017 .", "et al. 2017 . in", "al. 2017 . in the", "2017 . in the apoptosome", "in the apoptosome recruitment", "the apoptosome recruitment of", "apoptosome recruitment of caspase", "recruitment of caspase 9 may", "of caspase 9 may occur", "caspase 9 may occur before", "9 may occur before oligomerization", "may occur before oligomerization in", "occur before oligomerization in the", "before oligomerization in the card", "oligomerization in the card disk", "the card disk which", "card disk which presumably", "disk which presumably brings", "which presumably brings the caspase", "presumably brings the caspase domain", "brings the caspase domain into", "the caspase domain into proximity", "caspase domain into proximity for", "domain into proximity for their", "into proximity for their dimerization", "proximity for their dimerization and", "for their dimerization and activation", "dimerization and activation su", "and activation su tw", "activation su tw et", "et al. 2017 hu", "al. 2017 hu q", "2017 hu q et", "hu q et al. 2014", "et al. 2014 cheng", "al. 2014 cheng tc", "2014 cheng tc et", "cheng tc et al. 2016", "tc et al. 2016 .", "et al. 2016 . once", "al. 2016 . once activated", ". once activated casp9", "once activated casp9 activates", "activated casp9 activates downstream", "casp9 activates downstream effector caspases\u20113", "activates downstream effector caspases\u20113 and", "downstream effector caspases\u20113 and \u20117.", "effector caspases\u20113 and \u20117. the", "caspases\u20113 and \u20117. the activated", "and \u20117. the activated effector", "\u20117. the activated effector caspases", "the activated effector caspases then", "activated effector caspases then cleave", "effector caspases then cleave various", "caspases then cleave various cellular", "then cleave various cellular proteins.

", "cleave various cellular proteins.

different", "various cellular proteins.

different models", "cellular proteins.

different models have", "proteins.

different models have been", "different models have been proposed", "models have been proposed to", "have been proposed to explain", "been proposed to explain casp9", "proposed to explain casp9 activation:", "to explain casp9 activation: the", "explain casp9 activation: the \u201cproximity\u2011driven", "casp9 activation: the \u201cproximity\u2011driven dimerization", "activation: the \u201cproximity\u2011driven dimerization model\u201d", "the \u201cproximity\u2011driven dimerization model\u201d and", "\u201cproximity\u2011driven dimerization model\u201d and the", "dimerization model\u201d and the \u201cinduced", "model\u201d and the \u201cinduced conformation", "and the \u201cinduced conformation model\u201d.", "the \u201cinduced conformation model\u201d. the", "\u201cinduced conformation model\u201d. the first", "conformation model\u201d. the first models", "model\u201d. the first models states", "the first models states that", "first models states that upon", "models states that upon binding", "states that upon binding to", "that upon binding to heptameric", "upon binding to heptameric apaf1", "to heptameric apaf1 monomers", "heptameric apaf1 monomers of", "apaf1 monomers of procaspase\u20119", "monomers of procaspase\u20119 are brought", "of procaspase\u20119 are brought into", "procaspase\u20119 are brought into close", "are brought into close proximity", "brought into close proximity at", "into close proximity at a", "close proximity at a high", "proximity at a high concentration", "a high concentration acehan", "high concentration acehan et", "concentration acehan et al.", "et al. 2002 renatus", "al. 2002 renatus et", "2002 renatus et al.", "renatus et al. 2001 .", "et al. 2001 . this", "al. 2001 . this induces", "2001 . this induces dimerization", ". this induces dimerization which", "this induces dimerization which is", "induces dimerization which is sufficient", "dimerization which is sufficient for", "which is sufficient for casp9", "is sufficient for casp9 activation", "sufficient for casp9 activation whereas", "for casp9 activation whereas autoprocessing", "casp9 activation whereas autoprocessing within", "activation whereas autoprocessing within the", "whereas autoprocessing within the apoptosome", "autoprocessing within the apoptosome complex", "within the apoptosome complex merely", "the apoptosome complex merely stabilizes", "apoptosome complex merely stabilizes casp9", "complex merely stabilizes casp9 dimer", "stabilizes casp9 dimer boatright", "casp9 dimer boatright km", "dimer boatright km et", "boatright km et al. 2003", "et al. 2003 pop", "al. 2003 pop c", "2003 pop c et", "pop c et al. 2006", "c et al. 2006 .", "et al. 2006 . the", "al. 2006 . the \u201cinduced", "2006 . the \u201cinduced conformation", ". the \u201cinduced conformation model\u201d", "the \u201cinduced conformation model\u201d is", "\u201cinduced conformation model\u201d is based", "conformation model\u201d is based on", "model\u201d is based on the", "is based on the observation", "based on the observation that", "on the observation that casp9", "the observation that casp9 has", "observation that casp9 has a", "that casp9 has a much", "casp9 has a much higher", "has a much higher level", "a much higher level of", "much higher level of catalytic", "higher level of catalytic activity", "level of catalytic activity when", "of catalytic activity when it's", "catalytic activity when it's bound", "activity when it's bound to", "when it's bound to the", "it's bound to the apoptosome.", "bound to the apoptosome. the", "to the apoptosome. the model", "the apoptosome. the model suggests", "apoptosome. the model suggests that", "the model suggests that a", "model suggests that a conformational", "suggests that a conformational change", "that a conformational change occurs", "a conformational change occurs at", "conformational change occurs at the", "change occurs at the active", "occurs at the active site", "at the active site of", "the active site of casp9", "active site of casp9 upon", "site of casp9 upon binding", "of casp9 upon binding to", "casp9 upon binding to apaf1", "upon binding to apaf1 thus", "binding to apaf1 thus inducing", "to apaf1 thus inducing casp9", "apaf1 thus inducing casp9 homodimerization", "thus inducing casp9 homodimerization and", "inducing casp9 homodimerization and stabilizing", "casp9 homodimerization and stabilizing it", "homodimerization and stabilizing it in", "and stabilizing it in the", "stabilizing it in the catalytically", "it in the catalytically active", "in the catalytically active conformation", "catalytically active conformation shiozaki", "active conformation shiozaki en", "conformation shiozaki en et", "et al. 2002 . casp9", "al. 2002 . casp9 activation", "2002 . casp9 activation may", ". casp9 activation may also", "casp9 activation may also involve", "activation may also involve formation", "may also involve formation of", "also involve formation of a", "involve formation of a multimeric", "formation of a multimeric card:card", "of a multimeric card:card assembly", "a multimeric card:card assembly between", "multimeric card:card assembly between apaf1", "card:card assembly between apaf1 and", "assembly between apaf1 and procaspase\u20119", "apaf1 and procaspase\u20119 hu", "and procaspase\u20119 hu q", "procaspase\u20119 hu q et", "q et al. 2014 .
" ] }, { "record_id": "GLY_000594_1_10", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111459", "r hsa", "hsa 111459", "r hsa 111459" ] }, { "record_id": "GLY_000594_1_10", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of caspases", "caspases through", "through apoptosome", "apoptosome mediated", "mediated cleavage", "activation of caspases", "of caspases through", "caspases through apoptosome", "through apoptosome mediated", "apoptosome mediated cleavage", "activation of caspases through", "of caspases through apoptosome", "caspases through apoptosome mediated", "through apoptosome mediated cleavage", "activation of caspases through apoptosome", "of caspases through apoptosome mediated", "caspases through apoptosome mediated cleavage", "procaspase 3", "3 and", "and 7", "7 are", "are cleaved", "cleaved by", "by the", "the apoptosome.", "procaspase 3 and", "3 and 7", "and 7 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", "through chromatin.
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other transcription factors", "other transcription factors like", "transcription factors like ell", "like ell elongin", "ell elongin family", "elongin family members and", "family members and tfiif", "members and tfiif interact", "and tfiif interact directly", "tfiif interact directly with", "interact directly with elongating", "directly with elongating pol", "with elongating pol ii", "elongating pol ii and", "pol ii and increase", "ii and increase its", "and increase its elongation", "increase its elongation rate.", "elongation rate. these", "rate. these factors", "these factors have been", "factors have been observed", "have been observed to", "been observed to act", "observed to act on", "to act on naked", "act on naked dna", "on naked dna templates", "naked dna templates by", "dna templates by suppressing", "templates by suppressing transient", "by suppressing transient pausing", "suppressing transient pausing by", "transient pausing by the", "pausing by the enzyme", "by the enzyme at", "the enzyme at all", "enzyme at all or", "at all or most", "all or most steps", "or most steps of", "most steps of nucleotide", "steps of nucleotide addition.", "of nucleotide addition. in", "nucleotide addition. in drosophila", "in drosophila ell", "drosophila ell is", "ell is found at", "is found at a", "found at a large", "at a large number", "a large number of", "number of transcriptionally", "of transcriptionally active", "transcriptionally active sites on", "active sites on polytene", "sites on polytene chromosomes.", "polytene chromosomes. in", "chromosomes. in general", "in general ell", "general ell is", "ell is suspected to", "is suspected to have", "suspected to have more", "to have more unidentified", "have more unidentified functions.
", "more unidentified functions.
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", "polymerase through chromatin.
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", "have more unidentified functions.
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the gpvi receptor signaling", "gpvi receptor signaling cascade", "receptor signaling cascade is", "signaling cascade is similar", "cascade is similar to", "is similar to that", "similar to that of", "to that of t", "of t and", "t and b", "and b cell immune", "b cell immune receptors", "immune receptors involving", "receptors involving the", "involving the formation of", "the formation of a", "formation of a signalosome", "of a signalosome composed", "a signalosome composed of", "signalosome composed of adapter", "composed of adapter and", "of adapter and effector", "adapter and effector proteins.", "and effector proteins. at", "effector proteins. at the", "proteins. at the core", "at the core of", "the core of the", "core of the t", "of the t cell", "the t cell receptor", "t cell receptor signalosome", "cell receptor signalosome is", "receptor signalosome is the", "signalosome is the transmembrane", "is the transmembrane adapter", "the transmembrane adapter lat", "transmembrane adapter lat and", "adapter lat and two", "lat and two cytosolic", "and two cytosolic adapters", "two cytosolic adapters slp", "cytosolic adapters slp 76", "adapters slp 76 and", "slp 76 and gads.", "76 and gads. while", "and gads. while lat", "gads. while lat is", "while lat is essential", "lat is essential for", "is essential for signalling", "essential for signalling to", "for signalling to plcgamma1", "signalling to plcgamma1 downstream", "to plcgamma1 downstream of", "plcgamma1 downstream of the", "downstream of the t", "cell receptor the", "receptor the absence", "the absence of lat", "absence of lat in", "of lat in platelets", "lat in platelets only", "in platelets only impairs", "platelets only impairs the", "only impairs the activation", "impairs the activation of", "the activation of plcgamma2", "of plcgamma2 the", "plcgamma2 the response", "the response to collagen", "response to collagen and", "to collagen and gpvi", "collagen and gpvi receptor", "and gpvi receptor ligands", "gpvi receptor ligands remains", "receptor ligands remains sufficient", "ligands remains sufficient to", "remains sufficient to elicit", "sufficient to elicit a", "to elicit a full", "elicit a full aggregation", "a full aggregation response.", "full aggregation response. in", "aggregation response. in contrast", "in contrast gpvi", "contrast gpvi signalling", "gpvi signalling is almost", "signalling is almost entirely", "is almost entirely abolished", "almost entirely abolished in", "entirely abolished in the", "abolished in the absence", "in the absence of", "the absence of slp", "absence of slp 76.", "the gpvi receptor is a", "gpvi receptor is a complex", "receptor is a complex of", "is a complex of the", "a complex of the gpvi", "complex of the gpvi protein", "of the gpvi protein with", "the gpvi protein with fc", "gpvi protein with fc epsilon", "protein with fc epsilon r1", "with fc epsilon r1 gamma", "epsilon r1 gamma fcr", "r1 gamma fcr .", "gamma fcr . the", "fcr . the src family", ". the src family kinases", "the src family kinases fyn", "src family kinases fyn and", "family kinases fyn and lyn", "kinases fyn and lyn constitutively", "fyn and lyn constitutively associate", "and lyn constitutively associate with", "lyn constitutively associate with the", "constitutively associate with the gpvi", "associate with the gpvi fcr", "with the gpvi fcr complex", "the gpvi fcr complex in", "gpvi fcr complex in platelets", "fcr complex in platelets and", "complex in platelets and initiate", "in platelets and initiate platelet", "platelets and initiate platelet activation", "and initiate platelet activation through", "initiate platelet activation through phosphorylation", "platelet activation through phosphorylation of", "activation through phosphorylation of the", "through phosphorylation of the immunoreceptor", "phosphorylation of the immunoreceptor tyrosine", "of the immunoreceptor tyrosine based", "the immunoreceptor tyrosine based activation", "immunoreceptor tyrosine based activation motif", "based activation motif itam", "motif itam in", "itam in the fcr", "in the fcr gamma chain", "fcr gamma chain leading", "gamma chain leading to", "chain leading to binding", "leading to binding and activation", "to binding and activation of", "binding and activation of the", "and activation of the tyrosine", "activation of the tyrosine kinase", "of the tyrosine kinase syk.", "the tyrosine kinase syk. downstream", "tyrosine kinase syk. downstream of", "kinase syk. downstream of syk", "downstream of syk a", "of syk a series", "syk a series of", "a series of adapter molecules", "series of adapter molecules and", "of adapter molecules and effectors", "adapter molecules and effectors lead", "molecules and effectors lead to", "and effectors lead to platelet", "effectors lead to platelet activation.", "lead to platelet activation.

the", "to platelet activation.

the gpvi", "platelet activation.

the gpvi receptor", "activation.

the gpvi receptor signaling", "

the gpvi receptor signaling cascade", "gpvi receptor signaling cascade is", "receptor signaling cascade is similar", "signaling cascade is similar to", "cascade is similar to that", "is similar to that of", "similar to that of t", "that of t and", "of t and b", "t and b cell", "and b cell immune receptors", "cell immune receptors involving", "immune receptors involving the", "receptors involving the formation", "involving the formation of a", "the formation of a signalosome", "formation of a signalosome composed", "of a signalosome composed of", "a signalosome composed of adapter", "signalosome composed of adapter and", "composed of adapter and effector", "of adapter and effector proteins.", "adapter and effector proteins. at", "and effector proteins. at the", "effector proteins. at the core", "proteins. at the core of", "at the core of the", "the core of the t", "core of the t cell", "of the t cell receptor", "the t cell receptor signalosome", "t cell receptor signalosome is", "cell receptor signalosome is the", "receptor signalosome is the transmembrane", "signalosome is the transmembrane adapter", "is the transmembrane adapter lat", "the transmembrane adapter lat and", "transmembrane adapter lat and two", "adapter lat and two cytosolic", "lat and two cytosolic adapters", "and two cytosolic adapters slp", "two cytosolic adapters slp 76", "cytosolic adapters slp 76 and", "adapters slp 76 and gads.", "slp 76 and gads. while", "76 and gads. while lat", "and gads. while lat is", "gads. while lat is essential", "while lat is essential for", "lat is essential for signalling", "is essential for signalling to", "essential for signalling to plcgamma1", "for signalling to plcgamma1 downstream", "signalling to plcgamma1 downstream of", "to plcgamma1 downstream of the", "plcgamma1 downstream of the t", "downstream of the t cell", "t cell receptor the", "cell receptor the absence", "receptor the absence of", "the absence of lat in", "absence of lat in platelets", "of lat in platelets only", "lat in platelets only impairs", "in platelets only impairs the", "platelets only impairs the activation", "only impairs the activation of", "impairs the activation of plcgamma2", "activation of plcgamma2 the", "of plcgamma2 the response", "plcgamma2 the response to", "the response to collagen and", "response to collagen and gpvi", "to collagen and gpvi receptor", "collagen and gpvi receptor ligands", "and gpvi receptor ligands remains", "gpvi receptor ligands remains sufficient", "receptor ligands remains sufficient to", "ligands remains sufficient to elicit", "remains sufficient to elicit a", "sufficient to elicit a full", "to elicit a full aggregation", "elicit a full aggregation response.", "a full aggregation response. in", "full aggregation response. in contrast", "response. in contrast gpvi", "in contrast gpvi signalling", "contrast gpvi signalling is", "gpvi signalling is almost entirely", "signalling is almost entirely abolished", "is almost entirely abolished in", "almost entirely abolished in the", "entirely abolished in the absence", "abolished in the absence of", "in the absence of slp", "the absence of slp 76." ] }, { "record_id": "GLY_000594_1_22", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "114608", "r hsa", "hsa 114608", "r hsa 114608" ] }, { "record_id": "GLY_000594_1_22", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "platelet degranulation", "platelets function", "function as", "as exocytotic", "exocytotic cells", "secreting a", "a plethora", "plethora of", "of effector", "effector molecules", "molecules at", "at sites", "sites of", "of vascular", "vascular injury.", "injury. platelets", "platelets contain", "contain a", "a number", "number of", "of distinguishable", "distinguishable storage", "storage granules", "granules including", "including alpha", "alpha granules", "dense granules", "granules and", "and lysosomes.", "lysosomes. on", "on activation", "activation platelets", "platelets release", "release a", "a variety", "variety of", "of proteins", "largely from", "from storage", "granules but", "but also", "also as", "as the", "the result", "result of", "of apparent", "apparent cell", "cell lysis.", "lysis. these", "these act", "act in", "in an", "an autocrine", "autocrine or", "or paracrine", "paracrine fashion", "fashion to", "to modulate", "modulate cell", "cell signaling.", "signaling.


", "


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", "signaling.


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", "cell signaling.


alpha", "signaling.


alpha granules", "


alpha granules contain", "alpha granules contain mainly", "granules contain mainly polypeptides", "contain mainly polypeptides such", "mainly polypeptides such as", "such as fibrinogen", "fibrinogen von willebrand", "willebrand factor growth", "factor growth factors", "growth factors and protease", "factors and protease inhibitors", "and protease inhibitors that", "protease inhibitors that that", "inhibitors that that supplement", "that that supplement thrombin", "that supplement thrombin generation", "supplement thrombin generation at", "thrombin generation at the", "generation at the site", "at the site of", "the site of injury.", "site of injury. dense", "of injury. dense granules", "injury. dense granules contain", "dense granules contain small", "granules contain small molecules", "small molecules particularly", "molecules particularly adenosine", "adenosine diphosphate adp", "adp adenosine", "adenosine triphosphate atp", "atp serotonin", "and calcium all", "calcium all recruit", "all recruit platelets", "recruit platelets to", "platelets to the site", "to the site of", "site of injury. the", "of injury. the molecular", "injury. the molecular mechanism", "the molecular mechanism which", "molecular mechanism which facilitates", "mechanism which facilitates granule", "which facilitates granule release", "facilitates granule release involves", "granule release involves soluble", "release involves soluble nsf", "involves soluble nsf attachment", "soluble nsf attachment protein", "nsf attachment protein receptors", "protein receptors snares", "snares which", "which assemble into complexes", "assemble into complexes to", "into complexes to form", "complexes to form a", "to form a universal", "form a universal membrane", "a universal membrane fusion", "universal membrane fusion apparatus.", "membrane fusion apparatus. although", "fusion apparatus. although all", "apparatus. although all cells", "although all cells use", "all cells use snares", "cells use snares for", "use snares for membrane", "snares for membrane fusion", "membrane fusion different", "fusion different cells", "different cells possess different", "cells possess different snare", "possess different snare isoforms.", "different snare isoforms. platelets", "snare isoforms. platelets and", "isoforms. platelets and chromaffin", "platelets and chromaffin cells", "and chromaffin cells use", "chromaffin cells use many", "cells use many of", "use many of the", "many of the same", "of the same chaperone", "the same chaperone proteins", "same chaperone proteins to", "chaperone proteins to regulate", "proteins to regulate snare", "to regulate snare mediated", "regulate snare mediated secretion", "mediated secretion fitch", "secretion fitch tewfik", "fitch tewfik & flaumenhaft", "tewfik & flaumenhaft 2013", "& flaumenhaft 2013 .", "platelets function as exocytotic cells", "as exocytotic cells secreting", "exocytotic cells secreting a", "cells secreting a plethora", "secreting a plethora of effector", "a plethora of effector molecules", "plethora of effector molecules at", "of effector molecules at sites", "effector molecules at sites of", "molecules at sites of vascular", "at sites of vascular injury.", "sites of vascular injury. platelets", "of vascular injury. platelets contain", "vascular injury. platelets contain a", "injury. platelets contain a number", "platelets contain a number of", "contain a number of distinguishable", "a number of distinguishable storage", "number of distinguishable storage granules", "of distinguishable storage granules including", "distinguishable storage granules including alpha", "storage granules including alpha granules", "including alpha granules dense", "alpha granules dense granules", "granules dense granules and", "dense granules and lysosomes. on", "granules and lysosomes. on activation", "and lysosomes. on activation platelets", "lysosomes. on activation platelets release", "on activation platelets release a", "activation platelets release a variety", "platelets release a variety of", "release a variety of proteins", "variety of proteins largely", "of proteins largely from", "proteins largely from storage", "largely from storage granules but", "from storage granules but also", "storage granules but also as", "granules but also as the", "but also as the result", "also as the result of", "as the result of apparent", "the result of apparent cell", "result of apparent cell lysis.", "of apparent cell lysis. these", "apparent cell lysis. these act", "cell lysis. these act in", "lysis. these act in an", "these act in an autocrine", "act in an autocrine or", "in an autocrine or paracrine", "an autocrine or paracrine fashion", "autocrine or paracrine fashion to", "or paracrine fashion to modulate", "paracrine fashion to modulate cell", "fashion to modulate cell signaling.", "to modulate cell signaling.


", "modulate cell signaling.


alpha", "cell signaling.


alpha granules", "signaling.


alpha granules contain", "


alpha granules contain mainly", "alpha granules contain mainly polypeptides", "granules contain mainly polypeptides such", "contain mainly polypeptides such as", "polypeptides such as fibrinogen", "as fibrinogen von", "fibrinogen von willebrand factor", "von willebrand factor growth", "willebrand factor growth factors", "factor growth factors and", "growth factors and protease inhibitors", "factors and protease inhibitors that", "and protease inhibitors that that", "protease inhibitors that that supplement", "inhibitors that that supplement thrombin", "that that supplement thrombin generation", "that supplement thrombin generation at", "supplement thrombin generation at the", "thrombin generation at the site", "generation at the site of", "at the site of injury.", "the site of injury. dense", "site of injury. dense granules", "of injury. dense granules contain", "injury. dense granules contain small", "dense granules contain small molecules", "contain small molecules particularly", "small molecules particularly adenosine", "molecules particularly adenosine diphosphate", "particularly adenosine diphosphate adp", "adp adenosine triphosphate", "atp serotonin and", "serotonin and calcium all", "and calcium all recruit", "all recruit platelets to", "recruit platelets to the", "platelets to the site of", "to the site of injury.", "the site of injury. the", "site of injury. the molecular", "of injury. the molecular mechanism", "injury. the molecular mechanism which", "the molecular mechanism which facilitates", "molecular mechanism which facilitates granule", "mechanism which facilitates granule release", "which facilitates granule release involves", "facilitates granule release involves soluble", "granule release involves soluble nsf", "release involves soluble nsf attachment", "involves soluble nsf attachment protein", "soluble nsf attachment protein receptors", "attachment protein receptors snares", "snares which assemble", "which assemble into complexes to", "assemble into complexes to form", "into complexes to form a", "complexes to form a universal", "to form a universal membrane", "form a universal membrane fusion", "a universal membrane fusion apparatus.", "universal membrane fusion apparatus. although", "membrane fusion apparatus. although all", "fusion apparatus. although all cells", "apparatus. although all cells use", "although all cells use snares", "all cells use snares for", "cells use snares for membrane", "use snares for membrane fusion", "for membrane fusion different", "membrane fusion different cells", "fusion different cells possess", "different cells possess different snare", "cells possess different snare isoforms.", "possess different snare isoforms. platelets", "different snare isoforms. platelets and", "snare isoforms. platelets and chromaffin", "isoforms. platelets and chromaffin cells", "platelets and chromaffin cells use", "and chromaffin cells use many", "chromaffin cells use many of", "cells use many of the", "use many of the same", "many of the same chaperone", "of the same chaperone proteins", "the same chaperone proteins to", "same chaperone proteins to regulate", "chaperone proteins to regulate snare", "proteins to regulate snare mediated", "to regulate snare mediated secretion", "snare mediated secretion fitch", "mediated secretion fitch tewfik", "secretion fitch tewfik &", "fitch tewfik & flaumenhaft 2013", "tewfik & flaumenhaft 2013 ." ] }, { "record_id": "GLY_000594_1_23", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1169091", "r hsa", "hsa 1169091", "r hsa 1169091" ] }, { "record_id": "GLY_000594_1_23", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of nf", "nf kappab", "kappab in", "in b", "b cells", "activation of nf", "of nf kappab", "nf kappab in", "kappab in b", "in b cells", "activation of nf kappab", "of nf kappab in", "nf kappab in b", "kappab in b cells", "activation of nf kappab in", "of nf kappab in b", "nf kappab in b cells", "dag and", "and calcium", "calcium activate", "activate protein", "protein kinase", "kinase c", "c beta", "pkc beta", "kochs et", "et al.", "al. 1991", "which phosphorylates", "phosphorylates carma1", "carma1 and", "and other", "other proteins", "sommer et", "al. 2005", "2005 .", ". phosphorylated", "phosphorylated carma1", "carma1 recruits", "recruits bcl10", "bcl10 and", "and malt1", "malt1 to", "to form", "form the", "the cbm", "cbm complex", "tanner et", "al. 2007", "in turn", "recruits the", "the kinase", "kinase tak1", "tak1 and", "and the", "the ikk", "ikk complex", "shinohara et", "2005 using", "using chicken", "chicken cells", "cells .", ". tak1", "tak1 phosphorylates", "phosphorylates the", "ikk beta", "beta subunit", "activating it", "wang et", "al. 2001", "2001 .", ". the", "complex then", "then phosphorylates", "phosphorylates ikb", "ikb complexed", "complexed with", "with nf", "kappab dimers", "dimers in", "in the", "the cytosol", "zandi et", "al. 1998", "burke et", "al. 1999", "heilker et", "resulting in", "the degradation", "degradation of", "of ikb", "miyamoto et", "al. 1994", "traenckner et", "alkalay et", "al. 1995", "didonato et", "li et", "lin et", "scherer et", "chen et", "1995 .", ". nf", "dimers are", "are thereby", "thereby released", "released and", "and are", "are translocated", "translocated to", "to the", "the nucleus", "nucleus where", "where they", "they activate", "activate transcription", "baeuerle and", "and baltimore", "baltimore 1988", "blank et", "ghosh et", "al. 2008", "fagerlund et", "2008 .", "dag and calcium", "and calcium activate", "calcium activate protein", "activate protein kinase", "protein kinase c", "kinase c beta", "beta pkc", "beta kochs", "kochs et al.", "et al. 1991", "1991 which", "which phosphorylates carma1", "phosphorylates carma1 and", "carma1 and other", "and other proteins", "proteins sommer", "sommer et al.", "et al. 2005", "al. 2005 .", "2005 . phosphorylated", ". phosphorylated carma1", "phosphorylated carma1 recruits", "carma1 recruits bcl10", "recruits bcl10 and", "bcl10 and malt1", "and malt1 to", "malt1 to form", "to form the", "form the cbm", "the cbm complex", "complex sommer", "2005 tanner", "tanner et al.", "et al. 2007", "2007 which", "which in", "turn recruits", "recruits the kinase", "the kinase tak1", "kinase tak1 and", "tak1 and the", "and the ikk", "the ikk complex", "2005 shinohara", "shinohara et al.", "al. 2005 using", "2005 using chicken", "using chicken cells", "chicken cells .", "cells . tak1", ". tak1 phosphorylates", "tak1 phosphorylates the", "phosphorylates the ikk", "the ikk beta", "ikk beta subunit", "subunit activating", "it wang", "wang et al.", "et al. 2001", "al. 2001 .", "2001 . the", ". the ikk", "ikk complex then", "complex then phosphorylates", "then phosphorylates ikb", "phosphorylates ikb complexed", "ikb complexed with", "complexed with nf", "with nf kappab", "nf kappab dimers", "kappab dimers in", "dimers in the", "in the cytosol", "cytosol zandi", "zandi et al.", "et al. 1998", "1998 burke", "burke et al.", "et al. 1999", "1999 heilker", "heilker et al.", "resulting in the", "in the degradation", "the degradation of", "degradation of ikb", "ikb miyamoto", "miyamoto et al.", "et al. 1994", "1994 traenckner", "traenckner et al.", "1994 alkalay", "alkalay et al.", "et al. 1995", "1995 didonato", "didonato et al.", "1995 li", "li et al.", "1995 lin", "lin et al.", "1995 scherer", "scherer et al.", "1995 chen", "chen et al.", "al. 1995 .", "1995 . nf", ". nf kappab", "kappab dimers are", "dimers are thereby", "are thereby released", "thereby released and", "released and are", "and are translocated", "are translocated to", "translocated to the", "to the nucleus", "the nucleus where", "nucleus where they", "where they activate", "they activate transcription", "transcription baeuerle", "baeuerle and baltimore", "and baltimore 1988", "1988 blank", "blank et al.", "1991 ghosh", "ghosh et al.", "et al. 2008", "2008 fagerlund", "fagerlund et al.", "al. 2008 .", "dag and calcium activate", "and calcium activate protein", "calcium activate protein kinase", "activate protein kinase c", "protein kinase c beta", "c beta pkc", "beta pkc beta", "pkc beta kochs", "beta kochs et", "kochs et al. 1991", "al. 1991 which", "1991 which phosphorylates", "which phosphorylates carma1 and", "phosphorylates carma1 and other", "carma1 and other proteins", "other proteins sommer", "proteins sommer et", "sommer et al. 2005", "et al. 2005 .", "al. 2005 . phosphorylated", "2005 . phosphorylated carma1", ". phosphorylated carma1 recruits", "phosphorylated carma1 recruits bcl10", "carma1 recruits bcl10 and", "recruits bcl10 and malt1", "bcl10 and malt1 to", "and malt1 to form", "malt1 to form the", "to form the cbm", "form the cbm complex", "cbm complex sommer", "complex sommer et", "al. 2005 tanner", "2005 tanner et", "tanner et al. 2007", "al. 2007 which", "which in turn", "in turn recruits", "turn recruits the", "recruits the kinase tak1", "the kinase tak1 and", "kinase tak1 and the", "tak1 and the ikk", "and the ikk complex", "ikk complex sommer", "al. 2005 shinohara", "2005 shinohara et", "shinohara et al. 2005", "et al. 2005 using", "al. 2005 using chicken", "2005 using chicken cells", "using chicken cells .", "chicken cells . tak1", "cells . tak1 phosphorylates", ". tak1 phosphorylates the", "tak1 phosphorylates the ikk", "phosphorylates the ikk beta", "the ikk beta subunit", "beta subunit activating", "subunit activating it", "activating it wang", "it wang et", "wang et al. 2001", "et al. 2001 .", "al. 2001 . the", "2001 . the ikk", ". the ikk complex", "the ikk complex then", "ikk complex then phosphorylates", "complex then phosphorylates ikb", "then phosphorylates ikb complexed", "phosphorylates ikb complexed with", "ikb complexed with nf", "complexed with nf kappab", "with nf kappab dimers", "nf kappab dimers in", "kappab dimers in the", "dimers in the cytosol", "the cytosol zandi", "cytosol zandi et", "zandi et al. 1998", "al. 1998 burke", "1998 burke et", "burke et al. 1999", "al. 1999 heilker", "1999 heilker et", "heilker et al. 1999", "1999 resulting", "resulting in the degradation", "in the degradation of", "the degradation of ikb", "of ikb miyamoto", "ikb miyamoto et", "miyamoto et al. 1994", "al. 1994 traenckner", "1994 traenckner et", "traenckner et al. 1994", "al. 1994 alkalay", "1994 alkalay et", "alkalay et al. 1995", "al. 1995 didonato", "1995 didonato et", "didonato et al. 1995", "al. 1995 li", "1995 li et", "li et al. 1995", "al. 1995 lin", "1995 lin et", "lin et al. 1995", "al. 1995 scherer", "1995 scherer et", "scherer et al. 1995", "al. 1995 chen", "1995 chen et", "chen et al. 1995", "et al. 1995 .", "al. 1995 . nf", "1995 . nf kappab", ". nf kappab dimers", "nf kappab dimers are", "kappab dimers are thereby", "dimers are thereby released", "are thereby released and", "thereby released and are", "released and are translocated", "and are translocated to", "are translocated to the", "translocated to the nucleus", "to the nucleus where", "the nucleus where they", "nucleus where they activate", "where they activate transcription", "activate transcription baeuerle", "transcription baeuerle and", "baeuerle and baltimore 1988", "baltimore 1988 blank", "1988 blank et", "blank et al. 1991", "al. 1991 ghosh", "1991 ghosh et", "ghosh et al. 2008", "al. 2008 fagerlund", "2008 fagerlund et", "fagerlund et al. 2008", "et al. 2008 .", "dag and calcium activate protein", "and calcium activate protein kinase", "calcium activate protein kinase c", "activate protein kinase c beta", "kinase c beta pkc", "c beta pkc beta", "pkc beta kochs et", "beta kochs et al.", "et al. 1991 which", "al. 1991 which phosphorylates", "1991 which phosphorylates carma1", "which phosphorylates carma1 and other", "phosphorylates carma1 and other proteins", "and other proteins sommer", "other proteins sommer et", "proteins sommer et al.", "sommer et al. 2005 .", "et al. 2005 . phosphorylated", "al. 2005 . phosphorylated carma1", "2005 . phosphorylated carma1 recruits", ". phosphorylated carma1 recruits bcl10", "phosphorylated carma1 recruits bcl10 and", "carma1 recruits bcl10 and malt1", "recruits bcl10 and malt1 to", "bcl10 and malt1 to form", "and malt1 to form the", "malt1 to form the cbm", "to form the cbm complex", "the cbm complex sommer", "cbm complex sommer et", "complex sommer et al.", "et al. 2005 tanner", "al. 2005 tanner et", "2005 tanner et al.", "et al. 2007 which", "2007 which in", "in turn recruits the", "turn recruits the kinase", "recruits the kinase tak1 and", "the kinase tak1 and the", "kinase tak1 and the ikk", "tak1 and the ikk complex", "the ikk complex sommer", "ikk complex sommer et", "et al. 2005 shinohara", "al. 2005 shinohara et", "2005 shinohara et al.", "shinohara et al. 2005 using", "et al. 2005 using chicken", "al. 2005 using chicken cells", "2005 using chicken cells .", "using chicken cells . tak1", "chicken cells . tak1 phosphorylates", "cells . tak1 phosphorylates the", ". tak1 phosphorylates the ikk", "tak1 phosphorylates the ikk beta", "phosphorylates the ikk beta subunit", "ikk beta subunit activating", "beta subunit activating it", "activating it wang et", "it wang et al.", "wang et al. 2001 .", "et al. 2001 . the", "al. 2001 . the ikk", "2001 . the ikk complex", ". the ikk complex then", "the ikk complex then phosphorylates", "ikk complex then phosphorylates ikb", "complex then phosphorylates ikb complexed", "then phosphorylates ikb complexed with", "phosphorylates ikb complexed with nf", "ikb complexed with nf kappab", "complexed with nf kappab dimers", "with nf kappab dimers in", "nf kappab dimers in the", "kappab dimers in the cytosol", "in the cytosol zandi", "the cytosol zandi et", "cytosol zandi et al.", "et al. 1998 burke", "al. 1998 burke et", "1998 burke et al.", "et al. 1999 heilker", "al. 1999 heilker et", "1999 heilker et al.", "al. 1999 resulting", "1999 resulting in", "resulting in the degradation of", "in the degradation of ikb", "degradation of ikb miyamoto", "of ikb miyamoto et", "ikb miyamoto et al.", "et al. 1994 traenckner", "al. 1994 traenckner et", "1994 traenckner et al.", "et al. 1994 alkalay", "al. 1994 alkalay et", "1994 alkalay et al.", "et al. 1995 didonato", "al. 1995 didonato et", "1995 didonato et al.", "et al. 1995 li", "al. 1995 li et", "1995 li et al.", "et al. 1995 lin", "al. 1995 lin et", "1995 lin et al.", "et al. 1995 scherer", "al. 1995 scherer et", "1995 scherer et al.", "et al. 1995 chen", "al. 1995 chen et", "1995 chen et al.", "chen et al. 1995 .", "et al. 1995 . nf", "al. 1995 . nf kappab", "1995 . nf kappab dimers", ". nf kappab dimers are", "nf kappab dimers are thereby", "kappab dimers are thereby released", "dimers are thereby released and", "are thereby released and are", "thereby released and are translocated", "released and are translocated to", "and are translocated to the", "are translocated to the nucleus", "translocated to the nucleus where", "to the nucleus where they", "the nucleus where they activate", "nucleus where they activate transcription", "they activate transcription baeuerle", "activate transcription baeuerle and", "transcription baeuerle and baltimore", "and baltimore 1988 blank", "baltimore 1988 blank et", "1988 blank et al.", "et al. 1991 ghosh", "al. 1991 ghosh et", "1991 ghosh et al.", "et al. 2008 fagerlund", "al. 2008 fagerlund et", "2008 fagerlund et al.", "fagerlund et al. 2008 ." ] }, { "record_id": "GLY_000594_1_24", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1169408", "r hsa", "hsa 1169408", "r hsa 1169408" ] }, { "record_id": "GLY_000594_1_24", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "isg15 antiviral", "antiviral mechanism", "isg15 antiviral mechanism", "interferon stimulated", "stimulated gene", "gene 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is", "is then", "then transfered", "transfered from", "from e1", "e1 to", "to the", "the e2", "e2 conjugating", "conjugating enzyme", "enzyme ubch8", "ubch8 and", "and then", "then to", "the target", "target protein", "protein with", "with the", "the aid", "aid of", "of an", "an isg15", "isg15 e3", "e3 ligase", "such as", "as herc5", "herc5 and", "and efp.", "efp. hundreds", "hundreds of", "proteins for", "for isgylation", "isgylation have", "have been", "been identified.", "identified. several", "several proteins", "proteins that", "that are", "are part", "part of", "of antiviral", "antiviral signaling", "signaling pathways", "as rig", "rig i", "filamin b", "irf3 and", "and jak1", "been identified", "identified as", "as targets", "targets for", "for isgylation.", "isgylation. isg15", "isg15 also", "also conjugates", "conjugates some", "some viral", "viral proteins", "inhibiting viral", "viral budding", "budding and", "and release.", "release. isgylation", "isgylation appears", "appears to", "to act", "act either", "either by", "by disrupting", "disrupting the", "the activity", "activity of", "of a", "a target", "protein and/or", "and/or by", "by altering", "altering its", "its localization", "localization within", "within the", "the cell.", "interferon stimulated gene", "stimulated gene 15", "15 isg15", "is a member", "a member of", "member of the", "of the ubiquitin", "the ubiquitin like", "like ubl", "ubl family.", "family. it is", "it is strongly", "is strongly induced", "strongly induced upon", "induced upon exposure", "upon exposure to", "exposure to type", "to type i", "type i interferons", "interferons ifns", "viruses bacterial", "lps and", "and other stresses.", "other stresses. once", "stresses. once released", "once released the", "released the mature", "the mature isg15", "mature isg15 conjugates", "isg15 conjugates with", "conjugates with an", "with an array", "an array of", "array of target", "of target proteins", "proteins a", "a process 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to type i", "to type i interferons", "i interferons ifns", "ifns viruses", "viruses bacterial lps", "bacterial lps and", "lps and other", "and other stresses. once", "other stresses. once released", "stresses. once released the", "once released the mature", "released the mature isg15", "the mature isg15 conjugates", "mature isg15 conjugates with", "isg15 conjugates with an", "conjugates with an array", "with an array of", "an array of target", "array of target proteins", "target proteins a", "proteins a process", "a process termed isgylation.", "process termed isgylation. isgylation", "termed isgylation. isgylation utilizes", "isgylation. isgylation utilizes a", "isgylation utilizes a mechanism", "utilizes a mechanism similar", "a mechanism similar to", "mechanism similar to ubiquitination", "to ubiquitination requiring", "ubiquitination requiring a", "requiring a three step", "a three step enzymatic", "three step enzymatic cascade.", "step enzymatic cascade. ube1l", "enzymatic cascade. ube1l is", "cascade. ube1l is the", "ube1l is the isg15", "is the isg15 e1", "the isg15 e1 activating", "isg15 e1 activating enzyme", "e1 activating enzyme which", "activating enzyme which specifically", "enzyme which specifically activates", "which specifically activates isg15", "specifically activates isg15 at", "activates isg15 at the", "isg15 at the expense", "at the expense of", "the expense of atp.", "expense of atp. isg15", "of atp. isg15 is", "atp. isg15 is then", "isg15 is then transfered", "is then transfered from", "then transfered from e1", "transfered from e1 to", "from e1 to the", "e1 to the e2", "to the e2 conjugating", "the e2 conjugating enzyme", "e2 conjugating enzyme ubch8", "conjugating enzyme ubch8 and", "enzyme ubch8 and then", "ubch8 and then to", "and then to the", "then to the target", "to the target protein", "the target protein with", "target protein with the", "protein with the aid", "with the aid of", "the aid of an", "aid of an isg15", "of an 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"isgylation. isg15 also conjugates", "isg15 also conjugates some", "also conjugates some viral", "conjugates some viral proteins", "viral proteins inhibiting", "proteins inhibiting viral", "inhibiting viral budding and", "viral budding and release.", "budding and release. isgylation", "and release. isgylation appears", "release. isgylation appears to", "isgylation appears to act", "appears to act either", "to act either by", "act either by disrupting", "either by disrupting the", "by disrupting the activity", "disrupting the activity of", "the activity of a", "activity of a target", "of a target protein", "a target protein and/or", "target protein and/or by", "protein and/or by altering", "and/or by altering its", "by altering its localization", "altering its localization within", "its localization within the", "localization within the cell.", "stimulated gene 15 isg15", "15 isg15 is", "isg15 is a member", "is a member of the", "a member of the ubiquitin", "member of the ubiquitin like", "the ubiquitin like ubl", "like ubl family.", "ubl family. it is", "family. it is strongly induced", "it is strongly induced upon", "is strongly induced upon exposure", "strongly induced upon exposure to", "induced upon exposure to type", "upon exposure to type i", "exposure to type i interferons", "type i interferons ifns", "bacterial lps and other", "lps and other stresses.", "and other stresses. once released", "other stresses. once released the", "stresses. once released the mature", "once released the mature isg15", "released the mature isg15 conjugates", "the mature isg15 conjugates with", "mature isg15 conjugates with an", "isg15 conjugates with an array", "conjugates with an array of", "with an array of target", "an array of target proteins", "of target proteins a", "target proteins a process", "proteins a process termed", "a process termed isgylation. isgylation", "process termed isgylation. isgylation utilizes", "termed isgylation. isgylation utilizes a", "isgylation. isgylation utilizes a mechanism", "isgylation utilizes a mechanism similar", "utilizes a mechanism similar to", "a mechanism similar to ubiquitination", "similar to ubiquitination requiring", "to ubiquitination requiring a", "ubiquitination requiring a three", "requiring a three step enzymatic", "a three step enzymatic cascade.", "three step enzymatic cascade. ube1l", "step enzymatic cascade. ube1l is", "enzymatic cascade. ube1l is the", "cascade. ube1l is the isg15", "ube1l is the isg15 e1", "is the isg15 e1 activating", "the isg15 e1 activating enzyme", "isg15 e1 activating enzyme which", "e1 activating enzyme which specifically", "activating enzyme which specifically activates", "enzyme which specifically activates isg15", "which specifically activates isg15 at", "specifically activates isg15 at the", "activates isg15 at the expense", "isg15 at the expense of", "at the expense of atp.", "the expense of atp. isg15", "expense of atp. isg15 is", "of atp. isg15 is then", "atp. isg15 is then transfered", "isg15 is then transfered from", "is then transfered from e1", "then transfered from e1 to", "transfered from e1 to the", "from e1 to the e2", "e1 to the e2 conjugating", "to the e2 conjugating enzyme", "the e2 conjugating enzyme ubch8", "e2 conjugating enzyme ubch8 and", "conjugating enzyme ubch8 and then", "enzyme ubch8 and then to", "ubch8 and then to the", "and then to the target", "then to the target protein", "to the target protein with", "the target protein with the", "target protein with the aid", "protein with the aid of", "with the aid of an", "the aid of an isg15", "aid of an isg15 e3", "of an isg15 e3 ligase", "isg15 e3 ligase such", "e3 ligase such as", "ligase such as herc5", "such as herc5 and efp.", "as herc5 and efp. hundreds", "herc5 and efp. hundreds of", "and efp. hundreds of target", "efp. hundreds of target proteins", "hundreds of target proteins for", "of target proteins for isgylation", "target proteins for isgylation have", "proteins for 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proteins", "some viral proteins inhibiting", "viral proteins inhibiting viral", "proteins inhibiting viral budding", "inhibiting viral budding and release.", "viral budding and release. isgylation", "budding and release. isgylation appears", "and release. isgylation appears to", "release. isgylation appears to act", "isgylation appears to act either", "appears to act either by", "to act either by disrupting", "act either by disrupting the", "either by disrupting the activity", "by disrupting the activity of", "disrupting the activity of a", "the activity of a target", "activity of a target protein", "of a target protein and/or", "a target protein and/or by", "target protein and/or by altering", "protein and/or by altering its", "and/or by altering its localization", "by altering its localization within", "altering its localization within the", "its localization within the cell." ] }, { "record_id": "GLY_000594_1_25", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1181150", "r hsa", "hsa 1181150", "r hsa 1181150" ] }, { "record_id": "GLY_000594_1_25", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by nodal", "signaling by nodal", "nodal is", "is essential", "essential for", "for patterning", "patterning of", "of the", "the axes", "axes of", "the embryo", "embryo and", "and formation", "formation of", "of mesoderm", "mesoderm and", "and endoderm", "reviewed in", "in schier", "schier 2009", "shen 2007", "2007 .", ". the", "the nodal", "nodal proprotein", "proprotein is", "is secreted", "secreted and", "and cleaved", "cleaved extracellularly", "extracellularly to", "to yield", "yield mature", "mature nodal.", "nodal. mature", "mature nodal", "nodal homodimerizes", "homodimerizes and", "and can", "can also", "also form", "form heterodimers", "heterodimers with", "with lefty1", "or cerberus", "which negatively", "negatively regulate", "regulate nodal", "nodal 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"rns than", "than neutrophils", "nathan &", "& shiloh", "shiloh 2000", "2000 .

the", ".

the presence", "presence of", "of rons", "rons characterized", "characterized by", "by a", "a relatively", "relatively low", "low reactivity", "such as", "as h2o2", "o2\u02d9\u2212 or", "or no", "has no", "no deleterious", "deleterious effect", "effect on", "on biological", "biological environment", "attia sm", "sm 2010", "weidinger a", "& and", "and kozlov", "kozlov av", "av 2015", "2015 .", ". their", "their activity", "activity is", "is controlled", "controlled by", "by endogenous", "endogenous antioxidants", "both enzymatic", "enzymatic and", "and non", "non enzymatic", "that are", "are induced", "induced by", "by oxidative", "oxidative stress.", "stress. however", "however the", "the relatively", "low reactive", "reactive species", "species can", "can initiate", "initiate a", "a cascade", "cascade of", "of reactions", "reactions to", "to generate", "generate more", "more damaging", "damaging \u201csecondary\u201d", "\u201csecondary\u201d species", "species such", "as hydroxyl", "hydroxyl radical", "singlet oxygen", "oxygen or", "or peroxinitrite", "robinson jm", "jm 2008", "these \\secondary\\", "\\secondary\\ rons", "rons are", "are extremely", "extremely toxic", "toxic causing", "causing irreversible", "irreversible damage", "damage to", "to all", "all classes", "classes of", "of biomolecules", "2013 .

although", ".

although macrophages", "macrophages and", "and neutrophils", "neutrophils use", "use similar", "similar mechanisms", "mechanisms for", "for the", "the internalization", "internalization of", "of targets", "there are", "are differences", "differences in", "in how", "how they", "they perform", "perform phagocytosis", "phagocytosis and", "and in", "the final", "final outcome", "outcome of", "of the", "the process", "tapper h", "h &", "& grinstein", "grinstein s", "s 1997", "vierira ov", "ov et", "al. 2002", "2002 .", ". once", "once formed", "phagosome undergoes", "undergoes an", "an extensive", "extensive maturation", "maturation process", "process whereby", "whereby it", "it develops", "develops into", "a microbicidal", "microbicidal organelle", "organelle able", "to eliminate", "eliminate the", "the invading", "invading pathogen.", "pathogen. maturation", "maturation involves", "involves re", "re modeling", "modeling both", "both the", "the membrane", "membrane of", "phagosome and", "and its", "its luminal", "luminal contents", ". in", "phagosome formation", "formation and", "and maturation", "maturation follows", "follows a", "a series", "series of", "of strictly", "strictly coordinated", "coordinated membrane", "membrane fission/fusion", "fission/fusion events", "events between", "between the", "and compartments", "compartments of", "the endo/lysosomal", "endo/lysosomal network", "network gradually", "gradually transforming", "transforming the", "the nascent", "nascent phagosome", "phagosome into", "a phagolysosome", "a degradative", "degradative organelle", "organelle endowed", "endowed with", "with potent", "potent microbicidal", "microbicidal properties", "zimmerli s", "s et", ". neutrophils", "neutrophils instead", "instead contain", "contain a", "a large", "large number", "of preformed", "preformed granules", "granules such", "as azurophilic", "azurophilic and", "and specific", "specific granules", "granules that", "that can", "can rapidly", "rapidly fuse", "fuse with", "with phagosomes", "phagosomes delivering", "delivering antimicrobial", "antimicrobial substances", "karlsson a", "& dahlgren", "dahlgren c", "c 2002", "naucler c", "nordenfelt p", "p and", "and tapper", "h 2011", "2011 .", ". phagosomal", "phagosomal ph", "ph dynamics", "dynamics may", "may also", "also contribute", "contribute to", "the maturation", "process by", "by regulating", "regulating membrane", "membrane traffic", "traffic events.", "events. the", "the microbicidal", "microbicidal activity", "activity of", "of macrophages", "macrophages is", "is characterized", "by progressive", "progressive acidification", "acidification of", "the lumen", "down to", "to ph", "ph 4\u20135", "the proton", "proton pumping", "pumping vatpase.", "vatpase. a", "a low", "low ph", "ph is", "is a", "a prerequisite", "prerequisite for", "for optimal", "optimal enzymatic", "enzymatic activity", "of most", "most late", "late endosomal/lysosomal", "endosomal/lysosomal hydrolases", "hydrolases reported", "reported in", "in macrophages.", "macrophages. neutrophil", "neutrophil phagosome", "phagosome ph", "ph regulation", "regulation differs", "differs significantly", "significantly from", "from what", "what is", "is observed", "winterbourn cc", "cc et", "al. 2016", "2016 .", "the massive", "massive activation", "activation of", "the oxidative", "oxidative burst", "burst is", "is thought", "to result", "result in", "in early", "early alkalization", "alkalization of", "of neutrophil", "neutrophil phagosomes", "phagosomes which", "is linked", "linked to", "to proton", "proton consumption", "consumption during", "during the", "the generation", "generation of", "of hydrogen", "segal aw", "aw et", "al. 1981", "levine ap", "ap et", "al. 2015", ". other", "other studies", "studies showed", "showed that", "that neutrophil", "phagosome maintained", "maintained neutral", "neutral ph", "ph values", "values before", "before the", "the ph", "ph gradually", "gradually decreased", "jankowski a", "a et", ". neutrophil", "phagosomes also", "also exhibited", "exhibited a", "a high", "high proton", "proton leak", "which was", "was initiated", "initiated upon", "upon activation", "the nadph", "and this", "this activation", "activation counteracted", "counteracted phagosomal", "phagosomal acidification", "2002 .

the", ".

the reactome", "reactome module", "module describes", "describes ros", "production by", "by phagocytic", "phagocytic cells.", "cells. the", "the module", "module includes", "includes cell", "cell type", "type specific", "specific events", "for example", "mediated production", "of hypochlorous", "hypochlorous acid", "acid in", "in neutrophils.", "neutrophils. it", "it also", "also highlights", "highlights differences", "differences between", "between phagosomal", "dynamics in", "neutrophils and", "and macrophages.", "macrophages. the", "describes microbicidal", "of selective", "selective rons", "rons such", "radical or", "or peroxynitrite.", "peroxynitrite. however", "detection of", "of any", "any of", "of these", "these species", "species in", "the phagosomal", "phagosomal environment", "environment is", "is subject", "subject to", "to many", "many uncertainties", "n\u00fcsse o", "o 2011", "erard m", "m et", "al. 2018", "2018 .", "the mechanisms", "mechanisms by", "by which", "which reactive", "reactive oxygen/nitrogen", "oxygen/nitrogen species", "species kill", "kill pathogens", "pathogens in", "in phagocytic", "phagocytic immune", "immune cells", "are still", "still not", "not fully", "fully understood.", "the first line", "first line of", "line of defense", "of defense against", "defense against infectious", "against infectious agents", "infectious agents involves", "agents involves an", "involves an active", "an active recruitment", "active recruitment of", "recruitment of phagocytes", "of phagocytes to", "phagocytes to the", "to the site", "the site of", "site of infection.", "of infection. recruited", "infection. recruited cells", "recruited cells include", "cells include polymorhonuclear", "polymorhonuclear pmn", "pmn leukocytes", "leukocytes i.e.", "i.e. neutrophils", "monocytes/macrophages which", "which function together", "function together as", "together as innate", "as innate immunity", "innate immunity sentinels", "sentinels underhill", "underhill dm &", "dm & ozinsky", "& ozinsky a", "ozinsky a 2002", "2002 stuart", "stuart lm &", "lm & ezekowitz", "& ezekowitz ra", "ezekowitz ra 2005", "2005 flannagan", "flannagan rs et", "rs et al.", "et al. 2012", "al. 2012 .", "2012 . dendritic", ". dendritic cells", "dendritic cells are", "cells are also", "are also present", "present serving", "serving as important", "as important players", "important players in", "players in antigen", "in antigen presentation", "antigen presentation for", "presentation for ensuing", "for ensuing adaptive", "ensuing adaptive responses", "responses savina", "savina a &", "a & amigorena", "& amigorena s", "amigorena s 2007", "s 2007 .", "2007 . these", ". these cell", "these cell types", "cell types are", "types are able", "are able to", "able to bind", "to bind and", "bind and engulf", "and engulf invading", "engulf invading microbes", "invading microbes into", "microbes into a", "into a membrane", "a membrane enclosed", "membrane enclosed vacuole", "phagosome in", "in a process", "a process termed", "process termed phagocytosis.", "termed phagocytosis. phagocytosis", "phagocytosis. phagocytosis can", "phagocytosis can be", "can be defined", "be defined as", "defined as the", "as the receptor", "the receptor mediated", "receptor mediated engulfment", "mediated engulfment of", "engulfment of particles", "of particles greater", "particles greater than", "greater than 0.5", "than 0.5 micron", "0.5 micron in", "micron in diameter.", "in diameter. it", "diameter. it is", "it is initiated", "is initiated by", "initiated by the", "by the cross", "the cross linking", "cross linking of", "linking of host", "of host cell", "host cell membrane", "cell membrane receptors", "membrane receptors following", "receptors following engagement", "following engagement with", "engagement with their", "with their cognate", "their cognate ligands", "cognate ligands on", "ligands on the", "on the target", "the target surface", "surface underhill", "2012 . when", ". when engulfed", "when engulfed by", "engulfed by phagocytes", "phagocytes microorganisms", "microorganisms are exposed", "are exposed to", "exposed to a", "to a number", "a number of", "number of host", "of host defense", "host defense microbicidal", "defense microbicidal events", "microbicidal events within", "events within the", "within the resulting", "the resulting phagosome.", "resulting phagosome. these", "phagosome. these include", "these include the", "include the production", "the production of", "production of reactive", "of reactive oxygen", "reactive oxygen and", "oxygen and nitrogen", "and nitrogen species", "species ros", "rns rons", "rons by", "by specialized enzymes", "enzymes fang", "fang fc et", "fc et al.", "et al. 2004", "2004 kohchi", "kohchi c et", "c et al.", "et al. 2009", "2009 gostner", "gostner jm et", "jm et al.", "et al. 2013", "2013 vatansever", "vatansever f et", "f et al.", "al. 2013 .", "2013 . nadph", ". nadph oxidase", "oxidase nox", "nox complex", "complex consume oxygen", "consume oxygen to", "oxygen to produce", "to produce superoxide", "produce superoxide radical", "superoxide radical anion", "anion o2.", "and hydrogen peroxide", "peroxide h2o2", "robinson et al.", "al. 2004 .", "2004 . induced", ". induced no", "induced no synthase", "synthase inos", "inos is", "is involved in", "involved in the", "in the production", "production of no", "no which", "which is the", "is the primary", "the primary source", "primary source of", "source of all", "of all rns", "all rns in", "rns in biological", "in biological systems", "systems evans", "evans tg et", "tg et al.", "et al. 1996", "al. 1996 .", "1996 . the", ". the phagocyte", "the phagocyte nadph", "phagocyte nadph oxidase", "nadph oxidase and", "oxidase and inos", "and inos are", "inos are expressed", "are expressed in", "expressed in both", "in both pmn", "both pmn and", "pmn and mononuclear", "and mononuclear phagocytes", "mononuclear phagocytes and", "phagocytes and both", "and both cell", "both cell types", "cell types have", "types have the", "have the capacity", "the capacity for", "capacity for phagosomal", "for phagosomal burst", "phagosomal burst activity.", "burst activity. however", "the magnitude of", "magnitude of ros", "of ros generation", "ros generation in", "generation in neutrophils", "in neutrophils far", "neutrophils far exceeds", "far exceeds that", "exceeds that observed", "that observed in", "observed in macrophages", "macrophages vanderven", "vanderven bc et", "bc et al.", "al. 2009 .", "2009 . macrophages", ". macrophages are", "macrophages are thought", "are thought to", "thought to produce", "to produce considerably", "produce considerably more", "considerably more rns", "more rns than", "rns than neutrophils", "neutrophils fang", "2004 nathan", "nathan & shiloh", "& shiloh 2000", "shiloh 2000 .

the", "2000 .

the presence", ".

the presence of", "presence of rons", "of rons characterized", "rons characterized by", "characterized by a", "by a relatively", "a relatively low", "relatively low reactivity", "reactivity such", "such as h2o2", "h2o2 o2\u02d9\u2212", "o2\u02d9\u2212 or no", "no has", "has no deleterious", "no deleterious effect", "deleterious effect on", "effect on biological", "on biological environment", "environment attia", "attia sm 2010", "2010 weidinger", "weidinger a &", "a & and", "& and kozlov", "and kozlov av", "kozlov av 2015", "av 2015 .", "2015 . their", ". their activity", "their activity is", "activity is controlled", "is controlled by", "controlled by endogenous", "by endogenous antioxidants", "antioxidants both", "both enzymatic and", "enzymatic and non", "and non enzymatic", "enzymatic that", "that are induced", "are induced by", "induced by oxidative", "by oxidative stress.", "oxidative stress. however", "stress. however the", "however the relatively", "the relatively low", "relatively low reactive", "low reactive species", "reactive species can", "species can initiate", "can initiate a", "initiate a cascade", "a cascade of", "cascade of reactions", "of reactions to", "reactions to generate", "to generate more", "generate more damaging", "more damaging \u201csecondary\u201d", "damaging \u201csecondary\u201d species", "\u201csecondary\u201d species such", "species such as", "such as hydroxyl", "as hydroxyl radical", "radical \u2022oh", "singlet oxygen or", "oxygen or peroxinitrite", "peroxinitrite robinson", "robinson jm 2008", "2008 fang", "2004 . these", ". these \\secondary\\", "these \\secondary\\ rons", "\\secondary\\ rons are", "rons are extremely", "are extremely toxic", "extremely toxic causing", "toxic causing irreversible", "causing irreversible damage", "irreversible damage to", "damage to all", "to all classes", "all classes of", "classes of biomolecules", "biomolecules weidinger", "2015 fang", "al. 2013 .

although", "2013 .

although macrophages", ".

although macrophages and", "macrophages and neutrophils", "and neutrophils use", "neutrophils use similar", "use similar mechanisms", "similar mechanisms for", "mechanisms for the", "for the internalization", "the internalization of", "internalization of targets", "targets there", "there are differences", "are differences in", "differences in how", "in how they", "how they perform", "they perform phagocytosis", "perform phagocytosis and", "phagocytosis and in", "and in the", "in the final", "the final outcome", "final outcome of", "outcome of the", "of the process", "process tapper", "tapper h &", "h & grinstein", "& grinstein s", "grinstein s 1997", "1997 vierira", "vierira ov et", "ov et al.", "et al. 2002", "al. 2002 .", "2002 . once", ". once formed", "formed the", "the phagosome undergoes", "phagosome undergoes an", "undergoes an extensive", "an extensive maturation", "extensive maturation process", "maturation process whereby", "process whereby it", "whereby it develops", "it develops into", "develops into a", "into a microbicidal", "a microbicidal organelle", "microbicidal organelle able", "organelle able to", "able to eliminate", "to eliminate the", "eliminate the invading", "the invading pathogen.", "invading pathogen. maturation", "pathogen. maturation involves", "maturation involves re", "involves re modeling", "re modeling both", "modeling both the", "both the membrane", "the membrane of", "membrane of the", "of the phagosome", "the phagosome and", "phagosome and its", "and its luminal", "its luminal contents", "contents vierira", "2002 . in", ". in macrophages", "macrophages phagosome", "phagosome formation and", "formation and maturation", "and maturation follows", "maturation follows a", "follows a series", "a series of", "series of strictly", "of strictly coordinated", "strictly coordinated membrane", "coordinated membrane fission/fusion", "membrane fission/fusion events", "fission/fusion events between", "events between the", "between the phagosome", "phagosome and compartments", "and compartments of", "compartments of the", "of the endo/lysosomal", "the endo/lysosomal network", "endo/lysosomal network gradually", "network gradually transforming", "gradually transforming the", "transforming the nascent", "the nascent phagosome", "nascent phagosome into", "phagosome into a", "into a phagolysosome", "phagolysosome a", "a degradative organelle", "degradative organelle endowed", "organelle endowed with", "endowed with potent", "with potent microbicidal", "potent microbicidal properties", "properties zimmerli", "zimmerli s et", "s et al.", "1996 vierira", "2002 . neutrophils", ". neutrophils instead", "neutrophils instead contain", "instead contain a", "contain a large", "a large number", "large number of", "number of preformed", "of preformed granules", "preformed granules such", "granules such as", "such as azurophilic", "as azurophilic and", "azurophilic and specific", "and specific granules", "specific granules that", "granules that can", "that can rapidly", "can rapidly fuse", "rapidly fuse with", "fuse with phagosomes", "with phagosomes delivering", "phagosomes delivering antimicrobial", "delivering antimicrobial substances", "substances karlsson", "karlsson a &", "a & dahlgren", "& dahlgren c", "dahlgren c 2002", "2002 naucler", "naucler c et", "2002 nordenfelt", "nordenfelt p and", "p and tapper", "and tapper h", "tapper h 2011", "h 2011 .", "2011 . phagosomal", ". phagosomal ph", "phagosomal ph dynamics", "ph dynamics may", "dynamics may also", "may also contribute", "also contribute to", "contribute to the", "to the maturation", "the maturation process", "maturation process by", "process by regulating", "by regulating membrane", "regulating membrane traffic", "membrane traffic events.", "traffic events. the", "events. the microbicidal", "the microbicidal activity", "microbicidal activity of", "activity of macrophages", "of macrophages is", "macrophages is characterized", "is characterized by", "characterized by progressive", "by progressive acidification", "progressive acidification of", "acidification of the", "of the lumen", "lumen down", "down to ph", "to ph 4\u20135", "4\u20135 by", "by the proton", "the proton pumping", "proton pumping vatpase.", "pumping vatpase. a", "vatpase. a low", "a low ph", "low ph is", "ph is a", "is a prerequisite", "a prerequisite for", "prerequisite for optimal", "for optimal enzymatic", "optimal enzymatic activity", "enzymatic activity of", "activity of most", "of most late", "most late endosomal/lysosomal", "late endosomal/lysosomal hydrolases", "endosomal/lysosomal hydrolases reported", "hydrolases reported in", "reported in macrophages.", "in macrophages. neutrophil", "macrophages. neutrophil phagosome", "neutrophil phagosome ph", "phagosome ph regulation", "ph regulation differs", "regulation differs significantly", "differs significantly from", "significantly from what", "from what is", "what is observed", "is observed in", "macrophages nordenfelt", "2011 winterbourn", "winterbourn cc et", "cc et al.", "et al. 2016", "al. 2016 .", "2016 . the", ". the massive", "the massive activation", "massive activation of", "activation of the", "of the oxidative", "the oxidative burst", "oxidative burst is", "burst is thought", "is thought to", "thought to result", "to result in", "result in early", "in early alkalization", "early alkalization of", "alkalization of neutrophil", "of neutrophil phagosomes", "neutrophil phagosomes which", "phagosomes which is", "which is linked", "is linked to", "linked to proton", "to proton consumption", "proton consumption during", "consumption during the", "during the generation", "the generation of", "generation of hydrogen", "of hydrogen peroxide", "peroxide segal", "segal aw et", "aw et al.", "et al. 1981", "1981 levine", "levine ap et", "ap et al.", "et al. 2015", "al. 2015 .", "2015 . other", ". other studies", "other studies showed", "studies showed that", "showed that neutrophil", "that neutrophil phagosome", "neutrophil phagosome maintained", "phagosome maintained neutral", "maintained neutral ph", "neutral ph values", "ph values before", "values before the", "before the ph", "the ph gradually", "ph gradually decreased", "decreased jankowski", "jankowski a et", "a et al.", "2002 . neutrophil", ". neutrophil phagosomes", "neutrophil phagosomes also", "phagosomes also exhibited", "also exhibited a", "exhibited a high", "a high proton", "high proton leak", "leak which", "which was initiated", "was initiated upon", "initiated upon activation", "upon activation of", "of the nadph", "the nadph oxidase", "and this activation", "this activation counteracted", "activation counteracted phagosomal", "counteracted phagosomal acidification", "acidification jankowski", "al. 2002 .

the", "2002 .

the reactome", ".

the reactome module", "reactome module describes", "module describes ros", "describes ros and", "rns production by", "production by phagocytic", "by phagocytic cells.", "phagocytic cells. the", "cells. the module", "the module includes", "module includes cell", "includes cell type", "cell type specific", "type specific events", "events for", "example myeloperoxidase", "myeloperoxidase mpo", "mpo mediated", "mediated production of", "production of hypochlorous", "of hypochlorous acid", "hypochlorous acid in", "acid in neutrophils.", "in neutrophils. it", "neutrophils. it also", "it also highlights", "also highlights differences", "highlights differences between", "differences between phagosomal", "between phagosomal ph", "ph dynamics in", "dynamics in neutrophils", "in neutrophils and", "neutrophils and macrophages.", "and macrophages. the", "macrophages. the module", "the module describes", "module describes microbicidal", "describes microbicidal activity", "activity of selective", "of selective rons", "selective rons such", "rons such as", "hydroxyl radical or", "radical or peroxynitrite.", "or peroxynitrite. however", "however detection", "detection of any", "of any of", "any of these", "of these species", "these species in", "species in the", "in the phagosomal", "the phagosomal environment", "phagosomal environment is", "environment is subject", "is subject to", "subject to many", "to many uncertainties", "uncertainties n\u00fcsse", "n\u00fcsse o 2011", "2011 erard", "erard m et", "m et al.", "et al. 2018", "al. 2018 .", "2018 . the", ". the mechanisms", "the mechanisms by", "mechanisms by which", "by which reactive", "which reactive oxygen/nitrogen", "reactive oxygen/nitrogen species", "oxygen/nitrogen species kill", "species kill pathogens", "kill pathogens in", "pathogens in phagocytic", "in phagocytic immune", "phagocytic immune cells", "immune cells are", "cells are still", "are still not", "still not fully", "not fully understood.", "the first line of", "first line of defense", "line of defense against", "of defense against infectious", "defense against infectious agents", "against infectious agents involves", "infectious agents involves an", "agents involves an active", "involves an active recruitment", "an active recruitment of", "active recruitment of phagocytes", "recruitment of phagocytes to", "of phagocytes to the", "phagocytes to the site", "to the site of", "the site of infection.", "site of infection. recruited", "of infection. recruited cells", "infection. recruited cells include", "recruited cells include polymorhonuclear", "include polymorhonuclear pmn", "neutrophils and monocytes/macrophages", "and monocytes/macrophages which", "monocytes/macrophages which function", "which function together as", "function together as innate", "together as innate immunity", "as innate immunity sentinels", "immunity sentinels underhill", "sentinels underhill dm", "underhill dm & ozinsky", "dm & ozinsky a", "& ozinsky a 2002", "a 2002 stuart", "2002 stuart lm", "stuart lm & ezekowitz", "lm & ezekowitz ra", "& ezekowitz ra 2005", "ra 2005 flannagan", "2005 flannagan rs", "flannagan rs et al.", "rs et al. 2012", "et al. 2012 .", "al. 2012 . dendritic", "2012 . dendritic cells", ". dendritic cells are", "dendritic cells are also", "cells are also present", "also present serving", "present serving as", "serving as important players", "as important players in", "important players in antigen", "players in antigen presentation", "in antigen presentation for", "antigen presentation for ensuing", "presentation for ensuing adaptive", "for ensuing adaptive responses", "adaptive responses savina", "responses savina a", "savina a & amigorena", "a & amigorena s", "& amigorena s 2007", "amigorena s 2007 .", "s 2007 . these", "2007 . these cell", ". these cell types", "these cell types are", "cell types are able", "types are able to", "are able to bind", "able to bind and", "to bind and engulf", "bind and engulf invading", "and engulf invading microbes", "engulf invading microbes into", "invading microbes into a", "microbes into a membrane", "into a membrane enclosed", "a membrane enclosed vacuole", "vacuole the", "the phagosome in", "phagosome in a", "in a process termed", "a process termed phagocytosis.", "process termed phagocytosis. phagocytosis", "termed phagocytosis. phagocytosis can", "phagocytosis. phagocytosis can be", "phagocytosis can be defined", "can be defined as", "be defined as the", "defined as the receptor", "as the receptor mediated", "the receptor mediated engulfment", "receptor mediated engulfment of", "mediated engulfment of particles", "engulfment of particles greater", "of particles greater than", "particles greater than 0.5", "greater than 0.5 micron", "than 0.5 micron in", "0.5 micron in diameter.", "micron in diameter. it", "in diameter. it is", "diameter. it is initiated", "it is initiated by", "is initiated by the", "initiated by the cross", "by the cross linking", "the cross linking of", "cross linking of host", "linking of host cell", "of host cell membrane", "host cell membrane receptors", "cell membrane receptors following", "membrane receptors following engagement", "receptors following engagement with", "following engagement with their", "engagement with their cognate", "with their cognate ligands", "their cognate ligands on", "cognate ligands on the", "ligands on the target", "on the target surface", "target surface underhill", "surface underhill dm", "al. 2012 . when", "2012 . when engulfed", ". when engulfed by", "when engulfed by phagocytes", "by phagocytes microorganisms", "phagocytes microorganisms are", "microorganisms are exposed to", "are exposed to a", "exposed to a number", "to a number of", "a number of host", "number of host defense", "of host defense microbicidal", "host defense microbicidal events", "defense microbicidal events within", "microbicidal events within the", "events within the resulting", "within the resulting phagosome.", "the resulting phagosome. these", "resulting phagosome. these include", "phagosome. these include the", "these include the production", "include the production of", "the production of reactive", "production of reactive oxygen", "of reactive oxygen and", "reactive oxygen and nitrogen", "oxygen and nitrogen species", "nitrogen species ros", "species ros and", "and rns rons", "rons by specialized", "specialized enzymes fang", "enzymes fang fc", "fang fc et al.", "fc et al. 2004", "al. 2004 kohchi", "2004 kohchi c", "kohchi c et al.", "c et al. 2009", "al. 2009 gostner", "2009 gostner jm", "gostner jm et al.", "jm et al. 2013", "al. 2013 vatansever", "2013 vatansever f", "vatansever f et al.", "f et al. 2013", "et al. 2013 .", "al. 2013 . nadph", "2013 . nadph oxidase", "nadph oxidase nox", "nox complex consume", "complex consume oxygen to", "consume oxygen to produce", "oxygen to produce superoxide", "to produce superoxide radical", "produce superoxide radical anion", "radical anion o2.", "o2. and", "hydrogen peroxide h2o2", "h2o2 robinson", "robinson et al. 2004", "et al. 2004 .", "al. 2004 . induced", "2004 . induced no", ". induced no synthase", "no synthase inos", "inos is involved", "is involved in the", "involved in the production", "in the production of", "the production of no", "of no which", "no which is", "which is the primary", "is the primary source", "the primary source of", "primary source of all", "source of all rns", "of all rns in", "all rns in biological", "rns in biological systems", "biological systems evans", "systems evans tg", "evans tg et al.", "tg et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the phagocyte", ". the phagocyte nadph", "the phagocyte nadph oxidase", "phagocyte nadph oxidase and", "nadph oxidase and inos", "oxidase and inos are", "and inos are expressed", "inos are expressed in", "are expressed in both", "expressed in both pmn", "in both pmn and", "both pmn and mononuclear", "pmn and mononuclear phagocytes", "and mononuclear phagocytes and", "mononuclear phagocytes and both", "phagocytes and both cell", "and both cell types", "both cell types have", "cell types have the", "types have the capacity", "have the capacity for", "the capacity for phagosomal", "capacity for phagosomal burst", "for phagosomal burst activity.", "phagosomal burst activity. however", "activity. however the", "however the magnitude", "the magnitude of ros", "magnitude of ros generation", "of ros generation in", "ros generation in neutrophils", "generation in neutrophils far", "in neutrophils far exceeds", "neutrophils far exceeds that", "far exceeds that observed", "exceeds that observed in", "that observed in macrophages", "in macrophages vanderven", "macrophages vanderven bc", "vanderven bc et al.", "bc et al. 2009", "et al. 2009 .", "al. 2009 . macrophages", "2009 . macrophages are", ". macrophages are thought", "macrophages are thought to", "are thought to produce", "thought to produce considerably", "to produce considerably more", "produce considerably more rns", "considerably more rns than", "more rns than neutrophils", "than neutrophils fang", "neutrophils fang fc", "al. 2004 nathan", "2004 nathan &", "nathan & shiloh 2000", "& shiloh 2000 .

the", "shiloh 2000 .

the presence", "2000 .

the presence of", ".

the presence of rons", "presence of rons characterized", "of rons characterized by", "rons characterized by a", "characterized by a relatively", "by a relatively low", "a relatively low reactivity", "low reactivity such", "reactivity such as", "as h2o2 o2\u02d9\u2212", "h2o2 o2\u02d9\u2212 or", "or no has", "no has no", "has no deleterious effect", "no deleterious effect on", "deleterious effect on biological", "effect on biological environment", "biological environment attia", "environment attia sm", "sm 2010 weidinger", "2010 weidinger a", "weidinger a & and", "a & and kozlov", "& and kozlov av", "and kozlov av 2015", "kozlov av 2015 .", "av 2015 . their", "2015 . their activity", ". their activity is", "their activity is controlled", "activity is controlled by", "is controlled by endogenous", "controlled by endogenous antioxidants", "endogenous antioxidants both", "antioxidants both enzymatic", "both enzymatic and non", "enzymatic and non enzymatic", "non enzymatic that", "enzymatic that are", "that are induced by", "are induced by oxidative", "induced by oxidative stress.", "by oxidative stress. however", "oxidative stress. however the", "stress. however the relatively", "however the relatively low", "the relatively low reactive", "relatively low reactive species", "low reactive species can", "reactive species can initiate", "species can initiate a", "can initiate a cascade", "initiate a cascade of", "a cascade of reactions", "cascade of reactions to", "of reactions to generate", "reactions to generate more", "to generate more damaging", "generate more damaging \u201csecondary\u201d", "more damaging \u201csecondary\u201d species", "damaging \u201csecondary\u201d species such", "\u201csecondary\u201d species such as", "species such as hydroxyl", "such as hydroxyl radical", "hydroxyl radical \u2022oh", "\u2022oh singlet", "singlet oxygen or peroxinitrite", "or peroxinitrite robinson", "peroxinitrite robinson jm", "jm 2008 fang", "2008 fang fc", "al. 2004 . these", "2004 . these \\secondary\\", ". these \\secondary\\ rons", "these \\secondary\\ rons are", "\\secondary\\ rons are extremely", "rons are extremely toxic", "are extremely toxic causing", "extremely toxic causing irreversible", "toxic causing irreversible damage", "causing irreversible damage to", "irreversible damage to all", "damage to all classes", "to all classes of", "all classes of biomolecules", "of biomolecules weidinger", "biomolecules weidinger a", "av 2015 fang", "2015 fang fc", "et al. 2013 .

although", "al. 2013 .

although macrophages", "2013 .

although macrophages and", ".

although macrophages and neutrophils", "macrophages and neutrophils use", "and neutrophils use similar", "neutrophils use similar mechanisms", "use similar mechanisms for", "similar mechanisms for the", "mechanisms for the internalization", "for the internalization of", "the internalization of targets", "of targets there", "targets there are", "there are differences in", "are differences in how", "differences in how they", "in how they perform", "how they perform phagocytosis", "they perform phagocytosis and", "perform phagocytosis and in", "phagocytosis and in the", "and in the final", "in the final outcome", "the final outcome of", "final outcome of the", "outcome of the process", "the process tapper", "process tapper h", "tapper h & grinstein", "h & grinstein s", "& grinstein s 1997", "s 1997 vierira", "1997 vierira ov", "vierira ov et al.", "ov et al. 2002", "et al. 2002 .", "al. 2002 . once", "2002 . once formed", "once formed the", "formed the phagosome", "the phagosome undergoes an", "phagosome undergoes an extensive", "undergoes an extensive maturation", "an extensive maturation process", "extensive maturation process whereby", "maturation process whereby it", "process whereby it develops", "whereby it develops into", "it develops into a", "develops into a microbicidal", "into a microbicidal organelle", "a microbicidal organelle able", "microbicidal organelle able to", "organelle able to eliminate", "able to eliminate the", "to eliminate the invading", "eliminate the invading pathogen.", "the invading pathogen. maturation", "invading pathogen. maturation involves", "pathogen. maturation involves re", "maturation involves re modeling", "involves re modeling both", "re modeling both the", "modeling both the membrane", "both the membrane of", "the membrane of the", "membrane of the phagosome", "of the phagosome and", "the phagosome and its", "phagosome and its luminal", "and its luminal contents", "luminal contents vierira", "contents vierira ov", "al. 2002 . in", "2002 . in macrophages", "in macrophages phagosome", "macrophages phagosome formation", "phagosome formation and maturation", "formation and maturation follows", "and maturation follows a", "maturation follows a series", "follows a series of", "a series of strictly", "series of strictly coordinated", "of strictly coordinated membrane", "strictly coordinated membrane fission/fusion", "coordinated membrane fission/fusion events", "membrane fission/fusion events between", "fission/fusion events between the", "events between the phagosome", "between the phagosome and", "the phagosome and compartments", "phagosome and compartments of", "and compartments of the", "compartments of the endo/lysosomal", "of the endo/lysosomal network", "the endo/lysosomal network gradually", "endo/lysosomal network gradually transforming", "network gradually transforming the", "gradually transforming the nascent", "transforming the nascent phagosome", "the nascent phagosome into", "nascent phagosome into a", "phagosome into a phagolysosome", "a phagolysosome a", "phagolysosome a degradative", "a degradative organelle endowed", "degradative organelle endowed with", "organelle endowed with potent", "endowed with potent microbicidal", "with potent microbicidal properties", "microbicidal properties zimmerli", "properties zimmerli s", "zimmerli s et al.", "s et al. 1996", "al. 1996 vierira", "1996 vierira ov", "al. 2002 . neutrophils", "2002 . neutrophils instead", ". neutrophils instead contain", "neutrophils instead contain a", "instead contain a large", "contain a large number", "a large number of", "large number of preformed", "number of preformed granules", "of preformed granules such", "preformed granules such as", "granules such as azurophilic", "such as azurophilic and", "as azurophilic and specific", "azurophilic and specific granules", "and specific granules that", "specific granules that can", "granules that can rapidly", "that can rapidly fuse", "can rapidly fuse with", "rapidly fuse with phagosomes", "fuse with phagosomes delivering", "with phagosomes delivering antimicrobial", "phagosomes delivering antimicrobial substances", "antimicrobial substances karlsson", "substances karlsson a", "karlsson a & dahlgren", "a & dahlgren c", "& dahlgren c 2002", "c 2002 naucler", "2002 naucler c", "naucler c et al.", "c et al. 2002", "al. 2002 nordenfelt", "2002 nordenfelt p", "nordenfelt p and tapper", "p and tapper h", "and tapper h 2011", "tapper h 2011 .", "h 2011 . phagosomal", "2011 . phagosomal ph", ". phagosomal ph dynamics", "phagosomal ph dynamics may", "ph dynamics may also", "dynamics may also contribute", "may also contribute to", "also contribute to the", "contribute to the maturation", "to the maturation process", "the maturation process by", "maturation process by regulating", "process by regulating membrane", "by regulating membrane traffic", "regulating membrane traffic events.", "membrane traffic events. the", "traffic events. the microbicidal", "events. the microbicidal activity", "the microbicidal activity of", "microbicidal activity of macrophages", "activity of macrophages is", "of macrophages is characterized", "macrophages is characterized by", "is characterized by progressive", "characterized by progressive acidification", "by progressive acidification of", "progressive acidification of the", "acidification of the lumen", "the lumen down", "lumen down to", "down to ph 4\u20135", "ph 4\u20135 by", "4\u20135 by the", "by the proton pumping", "the proton pumping vatpase.", "proton pumping vatpase. a", "pumping vatpase. a low", "vatpase. a low ph", "a low ph is", "low ph is a", "ph is a prerequisite", "is a prerequisite for", "a prerequisite for optimal", "prerequisite for optimal enzymatic", "for optimal enzymatic activity", "optimal enzymatic activity of", "enzymatic activity of most", "activity of most late", "of most late endosomal/lysosomal", "most late endosomal/lysosomal hydrolases", "late endosomal/lysosomal hydrolases reported", "endosomal/lysosomal hydrolases reported in", "hydrolases reported in macrophages.", "reported in macrophages. neutrophil", "in macrophages. neutrophil phagosome", "macrophages. neutrophil phagosome ph", "neutrophil phagosome ph regulation", "phagosome ph regulation differs", "ph regulation differs significantly", "regulation differs significantly from", "differs significantly from what", "significantly from what is", "from what is observed", "what is observed in", "is observed in macrophages", "in macrophages nordenfelt", "macrophages nordenfelt p", "h 2011 winterbourn", "2011 winterbourn cc", "winterbourn cc et al.", "cc et al. 2016", "et al. 2016 .", "al. 2016 . the", "2016 . the massive", ". the massive activation", "the massive activation of", "massive activation of the", "activation of the oxidative", "of the oxidative burst", "the oxidative burst is", "oxidative burst is thought", "burst is thought to", "is thought to result", "thought to result in", "to result in early", "result in early alkalization", "in early alkalization of", "early alkalization of neutrophil", "alkalization of neutrophil phagosomes", "of neutrophil phagosomes which", "neutrophil phagosomes which is", "phagosomes which is linked", "which is linked to", "is linked to proton", "linked to proton consumption", "to proton consumption during", "proton consumption during the", "consumption during the generation", "during the generation of", "the generation of hydrogen", "generation of hydrogen peroxide", "hydrogen peroxide segal", "peroxide segal aw", "segal aw et al.", "aw et al. 1981", "al. 1981 levine", "1981 levine ap", "levine ap et al.", "ap et al. 2015", "et al. 2015 .", "al. 2015 . other", "2015 . other studies", ". other studies showed", "other studies showed that", "studies showed that neutrophil", "showed that neutrophil phagosome", "that neutrophil phagosome maintained", "neutrophil phagosome maintained neutral", "phagosome maintained neutral ph", "maintained neutral ph values", "neutral ph values before", "ph values before the", "values before the ph", "before the ph gradually", "the ph gradually decreased", "gradually decreased jankowski", "decreased jankowski a", "jankowski a et al.", "a et al. 2002", "al. 2002 . neutrophil", "2002 . neutrophil phagosomes", ". neutrophil phagosomes also", "neutrophil phagosomes also exhibited", "phagosomes also exhibited a", "also exhibited a high", "exhibited a high proton", "a high proton leak", "proton leak which", "leak which was", "which was initiated upon", "was initiated upon activation", "initiated upon activation of", "upon activation of the", "activation of the nadph", "of the nadph oxidase", "oxidase and this", "and this activation counteracted", "this activation counteracted phagosomal", "activation counteracted phagosomal acidification", "phagosomal acidification jankowski", "acidification jankowski a", "et al. 2002 .

the", "al. 2002 .

the reactome", "2002 .

the reactome module", ".

the reactome module describes", "reactome module describes ros", "module describes ros and", "describes ros and rns", "and rns production by", "rns production by phagocytic", "production by phagocytic cells.", "by phagocytic cells. the", "phagocytic cells. the module", "cells. the module includes", "the module includes cell", "module includes cell type", "includes cell type specific", "cell type specific events", "specific events for", "events for example", "for example myeloperoxidase", "mpo mediated production", "mediated production of hypochlorous", "production of hypochlorous acid", "of hypochlorous acid in", "hypochlorous acid in neutrophils.", "acid in neutrophils. it", "in neutrophils. it also", "neutrophils. it also highlights", "it also highlights differences", "also highlights differences between", "highlights differences between phagosomal", "differences between phagosomal ph", "between phagosomal ph dynamics", "phagosomal ph dynamics in", "ph dynamics in neutrophils", "dynamics in neutrophils and", "in neutrophils and macrophages.", "neutrophils and macrophages. the", "and macrophages. the module", "macrophages. the module describes", "the module describes microbicidal", "module describes microbicidal activity", "describes microbicidal activity of", "microbicidal activity of selective", "activity of selective rons", "of selective rons such", "selective rons such as", "rons such as hydroxyl", "as hydroxyl radical or", "hydroxyl radical or peroxynitrite.", "radical or peroxynitrite. however", "peroxynitrite. however detection", "however detection of", "detection of any of", "of any of these", "any of these species", "of these species in", "these species in the", "species in the phagosomal", "in the phagosomal environment", "the phagosomal environment is", "phagosomal environment is subject", "environment is subject to", "is subject to many", "subject to many uncertainties", "many uncertainties n\u00fcsse", "uncertainties n\u00fcsse o", "o 2011 erard", "2011 erard m", "erard m et al.", "m et al. 2018", "et al. 2018 .", "al. 2018 . the", "2018 . the mechanisms", ". the mechanisms by", "the mechanisms by which", "mechanisms by which reactive", "by which reactive oxygen/nitrogen", "which reactive oxygen/nitrogen species", "reactive oxygen/nitrogen species kill", "oxygen/nitrogen species kill pathogens", "species kill pathogens in", "kill pathogens in phagocytic", "pathogens in phagocytic immune", "in phagocytic immune cells", "phagocytic immune cells are", "immune cells are still", "cells are still not", "are still not fully", "still not fully understood.", "the first line of defense", "first line of defense against", "line of defense against infectious", "of defense against infectious agents", "defense against infectious agents involves", "against infectious agents involves an", "infectious agents involves an active", "agents involves an active recruitment", "involves an active recruitment of", "an active recruitment of phagocytes", "active recruitment of phagocytes to", "recruitment of phagocytes to the", "of phagocytes to the site", "phagocytes to the site of", "to the site of infection.", "the site of infection. recruited", "site of infection. recruited cells", "of infection. recruited cells include", "infection. recruited cells include polymorhonuclear", "cells include polymorhonuclear pmn", "polymorhonuclear pmn leukocytes", "pmn leukocytes i.e.", "leukocytes i.e. neutrophils", "i.e. neutrophils and", "and monocytes/macrophages which function", "monocytes/macrophages which function together", "which function together as innate", "function together as innate immunity", "together as innate immunity sentinels", "innate immunity sentinels underhill", "immunity sentinels underhill dm", "sentinels underhill dm &", "underhill dm & ozinsky a", "dm & ozinsky a 2002", "ozinsky a 2002 stuart", "a 2002 stuart lm", "2002 stuart lm &", "stuart lm & ezekowitz ra", "lm & ezekowitz ra 2005", "ezekowitz ra 2005 flannagan", "ra 2005 flannagan rs", "2005 flannagan rs et", "flannagan rs et al. 2012", "rs et al. 2012 .", "et al. 2012 . dendritic", "al. 2012 . dendritic cells", "2012 . dendritic cells are", ". dendritic cells are also", "dendritic cells are also present", "are also present serving", "also present serving as", "present serving as important", "serving as important players in", "as important players in antigen", "important players in antigen presentation", "players in antigen presentation for", "in antigen presentation for ensuing", "antigen presentation for ensuing adaptive", "presentation for ensuing adaptive responses", "ensuing adaptive responses savina", "adaptive responses savina a", "responses savina a &", "savina a & amigorena s", "a & amigorena s 2007", "& amigorena s 2007 .", "amigorena s 2007 . these", "s 2007 . these cell", "2007 . these cell types", ". these cell types are", "these cell types are able", "cell types are able to", "types are able to bind", "are able to bind and", "able to bind and engulf", "to bind and engulf invading", "bind and engulf invading microbes", "and engulf invading microbes into", "engulf invading microbes into a", "invading microbes into a membrane", "microbes into a membrane enclosed", "into a membrane enclosed vacuole", "enclosed vacuole the", "vacuole the phagosome", "the phagosome in a", "phagosome in a process", "in a process termed phagocytosis.", "a process termed phagocytosis. phagocytosis", "process termed phagocytosis. phagocytosis can", "termed phagocytosis. phagocytosis can be", "phagocytosis. phagocytosis can be defined", "phagocytosis can be defined as", "can be defined as the", "be defined as the receptor", "defined as the receptor mediated", "as the receptor mediated engulfment", "the receptor mediated engulfment of", "receptor mediated engulfment of particles", "mediated engulfment of particles greater", "engulfment of particles greater than", "of particles greater than 0.5", "particles greater than 0.5 micron", "greater than 0.5 micron in", "than 0.5 micron in diameter.", "0.5 micron in diameter. it", "micron in diameter. it is", "in diameter. it is initiated", "diameter. it is initiated by", "it is initiated by the", "is initiated by the cross", "initiated by the cross linking", "by the cross linking of", "the cross linking of host", "cross linking of host cell", "linking of host cell membrane", "of host cell membrane receptors", "host cell membrane receptors following", "cell membrane receptors following engagement", "membrane receptors following engagement with", "receptors following engagement with their", "following engagement with their cognate", "engagement with their cognate ligands", "with their cognate ligands on", "their cognate ligands on the", "cognate ligands on the target", "ligands on the target surface", "the target surface underhill", "target surface underhill dm", "surface underhill dm &", "et al. 2012 . when", "al. 2012 . when engulfed", "2012 . when engulfed by", ". when engulfed by phagocytes", "engulfed by phagocytes microorganisms", "by phagocytes microorganisms are", "phagocytes microorganisms are exposed", "microorganisms are exposed to a", "are exposed to a number", "exposed to a number of", "to a number of host", "a number of host defense", "number of host defense microbicidal", "of host defense microbicidal events", "host defense microbicidal events within", "defense microbicidal events within the", "microbicidal events within the resulting", "events within the resulting phagosome.", "within the resulting phagosome. these", "the resulting phagosome. these include", "resulting phagosome. these include the", "phagosome. these include the production", "these include the production of", "include the production of reactive", "the production of reactive oxygen", "production of reactive oxygen and", "of reactive oxygen and nitrogen", "reactive oxygen and nitrogen species", "and nitrogen species ros", "nitrogen species ros and", "species ros and rns", "ros and rns rons", "rns rons by", "rons by specialized enzymes", "by specialized enzymes fang", "specialized enzymes fang fc", "enzymes fang fc et", "fang fc et al. 2004", "et al. 2004 kohchi", "al. 2004 kohchi c", "2004 kohchi c et", "kohchi c et al. 2009", "et al. 2009 gostner", "al. 2009 gostner jm", "2009 gostner jm et", "gostner jm et al. 2013", "et al. 2013 vatansever", "al. 2013 vatansever f", "2013 vatansever f et", "vatansever f et al. 2013", "f et al. 2013 .", "et al. 2013 . nadph", "al. 2013 . nadph oxidase", ". nadph oxidase nox", "oxidase nox complex", "nox complex consume oxygen", "complex consume oxygen to produce", "consume oxygen to produce superoxide", "oxygen to produce superoxide radical", "to produce superoxide radical anion", "superoxide radical anion o2.", "o2. and hydrogen", "and hydrogen peroxide h2o2", "h2o2 robinson et", "robinson et al. 2004 .", "et al. 2004 . induced", "al. 2004 . induced no", "2004 . induced no synthase", "induced no synthase inos", "synthase inos is", "inos is involved in", "is involved in the production", "involved in the production of", "in the production of no", "production of no which", "of no which is", "no which is the", "which is the primary source", "is the primary source of", "the primary source of all", "primary source of all rns", "source of all rns in", "of all rns in biological", "all rns in biological systems", "in biological systems evans", "biological systems evans tg", "systems evans tg et", "evans tg et al. 1996", "tg et al. 1996 .", "et al. 1996 . the", "al. 1996 . the phagocyte", "1996 . the phagocyte nadph", ". the phagocyte nadph oxidase", "the phagocyte nadph oxidase and", "phagocyte nadph oxidase and inos", "nadph oxidase and inos are", "oxidase and inos are expressed", "and inos are expressed in", "inos are expressed in both", "are expressed in both pmn", "expressed in both pmn and", "in both pmn and mononuclear", "both pmn and mononuclear phagocytes", "pmn and mononuclear phagocytes and", "and mononuclear phagocytes and both", "mononuclear phagocytes and both cell", "phagocytes and both cell types", "and both cell types have", "both cell types have the", "cell types have the capacity", "types have the capacity for", "have the capacity for phagosomal", "the capacity for phagosomal burst", "capacity for phagosomal burst activity.", "for phagosomal burst activity. however", "burst activity. however the", "activity. however the magnitude", "however the magnitude of", "the magnitude of ros generation", "magnitude of ros generation in", "of ros generation in neutrophils", "ros generation in neutrophils far", "generation in neutrophils far exceeds", "in neutrophils far exceeds that", "neutrophils far exceeds that observed", "far exceeds that observed in", "exceeds that observed in macrophages", "observed in macrophages vanderven", "in macrophages vanderven bc", "macrophages vanderven bc et", "vanderven bc et al. 2009", "bc et al. 2009 .", "et al. 2009 . macrophages", "al. 2009 . macrophages are", "2009 . macrophages are thought", ". macrophages are thought to", "macrophages are thought to produce", "are thought to produce considerably", "thought to produce considerably more", "to produce considerably more rns", "produce considerably more rns than", "considerably more rns than neutrophils", "rns than neutrophils fang", "than neutrophils fang fc", "neutrophils fang fc et", "et al. 2004 nathan", "al. 2004 nathan &", "2004 nathan & shiloh", "nathan & shiloh 2000 .

the", "& shiloh 2000 .

the presence", "shiloh 2000 .

the presence of", "2000 .

the presence of rons", ".

the presence of rons characterized", "presence of rons characterized by", "of rons characterized by a", "rons characterized by a relatively", "characterized by a relatively low", "by a relatively low reactivity", "relatively low reactivity such", "low reactivity such as", "reactivity such as h2o2", "such as h2o2 o2\u02d9\u2212", "as h2o2 o2\u02d9\u2212 or", "h2o2 o2\u02d9\u2212 or no", "o2\u02d9\u2212 or no has", "or no has no", "no has no deleterious", "has no deleterious effect on", "no deleterious effect on biological", "deleterious effect on biological environment", "on biological environment attia", "biological environment attia sm", "environment attia sm 2010", "attia sm 2010 weidinger", "sm 2010 weidinger a", "2010 weidinger a &", "weidinger a & and kozlov", "a & and kozlov av", "& and kozlov av 2015", "and kozlov av 2015 .", "kozlov av 2015 . their", "av 2015 . their activity", "2015 . their activity is", ". their activity is controlled", "their activity is controlled by", "activity is controlled by endogenous", "is controlled by endogenous antioxidants", "by endogenous antioxidants both", "endogenous antioxidants both enzymatic", "antioxidants both enzymatic and", "both enzymatic and non enzymatic", "and non enzymatic that", "non enzymatic that are", "enzymatic that are induced", "that are induced by oxidative", "are induced by oxidative stress.", "induced by oxidative stress. however", "by oxidative stress. however the", "oxidative stress. however the relatively", "stress. however the relatively low", "however the relatively low reactive", "the relatively low reactive species", "relatively low reactive species can", "low reactive species can initiate", "reactive species can initiate a", "species can initiate a cascade", "can initiate a cascade of", "initiate a cascade of reactions", "a cascade of reactions to", "cascade of reactions to generate", "of reactions to generate more", "reactions to generate more damaging", "to generate more damaging \u201csecondary\u201d", "generate more damaging \u201csecondary\u201d species", "more damaging \u201csecondary\u201d species such", "damaging \u201csecondary\u201d species such as", "\u201csecondary\u201d species such as hydroxyl", "species such as hydroxyl radical", "as hydroxyl radical \u2022oh", "\u2022oh singlet oxygen", "oxygen or peroxinitrite robinson", "or peroxinitrite robinson jm", "peroxinitrite robinson jm 2008", "robinson jm 2008 fang", "jm 2008 fang fc", "2008 fang fc et", "fc et al. 2004 .", "et al. 2004 . these", "al. 2004 . these \\secondary\\", "2004 . these \\secondary\\ rons", ". these \\secondary\\ rons are", "these \\secondary\\ rons are extremely", "\\secondary\\ rons are extremely toxic", "rons are extremely toxic causing", "are extremely toxic causing irreversible", "extremely toxic causing irreversible damage", "toxic causing irreversible damage to", "causing irreversible damage to all", "irreversible damage to all classes", "damage to all classes of", "to all classes of biomolecules", "classes of biomolecules weidinger", "of biomolecules weidinger a", "biomolecules weidinger a &", "kozlov av 2015 fang", "av 2015 fang fc", "2015 fang fc et", "f et al. 2013 .

although", "et al. 2013 .

although macrophages", "al. 2013 .

although macrophages and", "2013 .

although macrophages and neutrophils", ".

although macrophages and neutrophils use", "macrophages and neutrophils use similar", "and neutrophils use similar mechanisms", "neutrophils use similar mechanisms for", "use similar mechanisms for the", "similar mechanisms for the internalization", "mechanisms for the internalization of", "for the internalization of targets", "internalization of targets there", "of targets there are", "targets there are differences", "there are differences in how", "are differences in how they", "differences in how they perform", "in how they perform phagocytosis", "how they perform phagocytosis and", "they perform phagocytosis and in", "perform phagocytosis and in the", "phagocytosis and in the final", "and in the final outcome", "in the final outcome of", "the final outcome of the", "final outcome of the process", "of the process tapper", "the process tapper h", "process tapper h &", "tapper h & grinstein s", "h & grinstein s 1997", "grinstein s 1997 vierira", "s 1997 vierira ov", "1997 vierira ov et", "vierira ov et al. 2002", "ov et al. 2002 .", "et al. 2002 . once", "al. 2002 . once formed", ". once formed the", "once formed the phagosome", "formed the phagosome undergoes", "the phagosome undergoes an extensive", "phagosome undergoes an extensive maturation", "undergoes an extensive maturation process", "an extensive maturation process whereby", "extensive maturation process whereby it", "maturation process whereby it develops", "process whereby it develops into", "whereby it develops into a", "it develops into a microbicidal", "develops into a microbicidal organelle", "into a microbicidal organelle able", "a microbicidal organelle able to", "microbicidal organelle able to eliminate", "organelle able to eliminate the", "able to eliminate the invading", "to eliminate the invading pathogen.", "eliminate the invading pathogen. maturation", "the invading pathogen. maturation involves", "invading pathogen. maturation involves re", "pathogen. maturation involves re modeling", "maturation involves re modeling both", "involves re modeling both the", "re modeling both the membrane", "modeling both the membrane of", "both the membrane of the", "the membrane of the phagosome", "membrane of the phagosome and", "of the phagosome and its", "the phagosome and its luminal", "phagosome and its luminal contents", "its luminal contents vierira", "luminal contents vierira ov", "contents vierira ov et", "et al. 2002 . in", "al. 2002 . in macrophages", ". in macrophages phagosome", "in macrophages phagosome formation", "macrophages phagosome formation and", "phagosome formation and maturation follows", "formation and maturation follows a", "and maturation follows a series", "maturation follows a series of", "follows a series of strictly", "a series of strictly coordinated", "series of strictly coordinated membrane", "of strictly coordinated membrane fission/fusion", "strictly coordinated membrane fission/fusion events", "coordinated membrane fission/fusion events between", "membrane fission/fusion events between the", "fission/fusion events between the phagosome", "events between the phagosome and", "between the phagosome and compartments", "the phagosome and compartments of", "phagosome and compartments of the", "and compartments of the endo/lysosomal", "compartments of the endo/lysosomal network", "of the endo/lysosomal network gradually", "the endo/lysosomal network gradually transforming", "endo/lysosomal network gradually transforming the", "network gradually transforming the nascent", "gradually transforming the nascent phagosome", "transforming the nascent phagosome into", "the nascent phagosome into a", "nascent phagosome into a phagolysosome", "into a phagolysosome a", "a phagolysosome a degradative", "phagolysosome a degradative organelle", "a degradative organelle endowed with", "degradative organelle endowed with potent", "organelle endowed with potent microbicidal", "endowed with potent microbicidal properties", "potent microbicidal properties zimmerli", "microbicidal properties zimmerli s", "properties zimmerli s et", "zimmerli s et al. 1996", "et al. 1996 vierira", "al. 1996 vierira ov", "1996 vierira ov et", "et al. 2002 . neutrophils", "al. 2002 . neutrophils instead", "2002 . neutrophils instead contain", ". neutrophils instead contain a", "neutrophils instead contain a large", "instead contain a large number", "contain a large number of", "a large number of preformed", "large number of preformed granules", "number of preformed granules such", "of preformed granules such as", "preformed granules such as azurophilic", "granules such as azurophilic and", "such as azurophilic and specific", "as azurophilic and specific granules", "azurophilic and specific granules that", "and specific granules that can", "specific granules that can rapidly", "granules that can rapidly fuse", "that can rapidly fuse with", "can rapidly fuse with phagosomes", "rapidly fuse with phagosomes delivering", "fuse with phagosomes delivering antimicrobial", "with phagosomes delivering antimicrobial substances", "delivering antimicrobial substances karlsson", "antimicrobial substances karlsson a", "substances karlsson a &", "karlsson a & dahlgren c", "a & dahlgren c 2002", "dahlgren c 2002 naucler", "c 2002 naucler c", "2002 naucler c et", "naucler c et al. 2002", "et al. 2002 nordenfelt", "al. 2002 nordenfelt p", "2002 nordenfelt p and", "nordenfelt p and tapper h", "p and tapper h 2011", "and tapper h 2011 .", "tapper h 2011 . phagosomal", "h 2011 . phagosomal ph", "2011 . phagosomal ph dynamics", ". phagosomal ph dynamics may", "phagosomal ph dynamics may also", "ph dynamics may also contribute", "dynamics may also contribute to", "may also contribute to the", "also contribute to the maturation", "contribute to the maturation process", "to the maturation process by", "the maturation process by regulating", "maturation process by regulating membrane", "process by regulating membrane traffic", "by regulating membrane traffic events.", "regulating membrane traffic events. the", "membrane traffic events. the microbicidal", "traffic events. the microbicidal activity", "events. the microbicidal activity of", "the microbicidal activity of macrophages", "microbicidal activity of macrophages is", "activity of macrophages is characterized", "of macrophages is characterized by", "macrophages is characterized by progressive", "is characterized by progressive acidification", "characterized by progressive acidification of", "by progressive acidification of the", "progressive acidification of the lumen", "of the lumen down", "the lumen down to", "lumen down to ph", "to ph 4\u20135 by", "ph 4\u20135 by the", "4\u20135 by the proton", "by the proton pumping vatpase.", "the proton pumping vatpase. a", "proton pumping vatpase. a low", "pumping vatpase. a low ph", "vatpase. a low ph is", "a low ph is a", "low ph is a prerequisite", "ph is a prerequisite for", "is a prerequisite for optimal", "a prerequisite for optimal enzymatic", "prerequisite for optimal enzymatic activity", "for optimal enzymatic activity of", "optimal enzymatic activity of most", "enzymatic activity of most late", "activity of most late endosomal/lysosomal", "of most late endosomal/lysosomal hydrolases", "most late endosomal/lysosomal hydrolases reported", "late endosomal/lysosomal hydrolases reported in", "endosomal/lysosomal hydrolases reported in macrophages.", "hydrolases reported in macrophages. neutrophil", "reported in macrophages. neutrophil phagosome", "in macrophages. neutrophil phagosome ph", "macrophages. neutrophil phagosome ph regulation", "neutrophil phagosome ph regulation differs", "phagosome ph regulation differs significantly", "ph regulation differs significantly from", "regulation differs significantly from what", "differs significantly from what is", "significantly from what is observed", "from what is observed in", "what is observed in macrophages", "observed in macrophages nordenfelt", "in macrophages nordenfelt p", "macrophages nordenfelt p and", "tapper h 2011 winterbourn", "h 2011 winterbourn cc", "2011 winterbourn cc et", "winterbourn cc et al. 2016", "cc et al. 2016 .", "et al. 2016 . the", "al. 2016 . the massive", "2016 . the massive activation", ". the massive activation of", "the massive activation of the", "massive activation of the oxidative", "activation of the oxidative burst", "of the oxidative burst is", "the oxidative burst is thought", "oxidative burst is thought to", "burst is thought to result", "is thought to result in", "thought to result in early", "to result in early alkalization", "result in early alkalization of", "in early alkalization of neutrophil", "early alkalization of neutrophil phagosomes", "alkalization of neutrophil phagosomes which", "of neutrophil phagosomes which is", "neutrophil phagosomes which is linked", "phagosomes which is linked to", "which is linked to proton", "is linked to proton consumption", "linked to proton consumption during", "to proton consumption during the", "proton consumption during the generation", "consumption during the generation of", "during the generation of hydrogen", "the generation of hydrogen peroxide", "of hydrogen peroxide segal", "hydrogen peroxide segal aw", "peroxide segal aw et", "segal aw et al. 1981", "et al. 1981 levine", "al. 1981 levine ap", "1981 levine ap et", "levine ap et al. 2015", "ap et al. 2015 .", "et al. 2015 . other", "al. 2015 . other studies", "2015 . other studies showed", ". other studies showed that", "other studies showed that neutrophil", "studies showed that neutrophil phagosome", "showed that neutrophil phagosome maintained", "that neutrophil phagosome maintained neutral", "neutrophil phagosome maintained neutral ph", "phagosome maintained neutral ph values", "maintained neutral ph values before", "neutral ph values before the", "ph values before the ph", "values before the ph gradually", "before the ph gradually decreased", "ph gradually decreased jankowski", "gradually decreased jankowski a", "decreased jankowski a et", "jankowski a et al. 2002", "a et al. 2002 .", "et al. 2002 . neutrophil", "al. 2002 . neutrophil phagosomes", "2002 . neutrophil phagosomes also", ". neutrophil phagosomes also exhibited", "neutrophil phagosomes also exhibited a", "phagosomes also exhibited a high", "also exhibited a high proton", "exhibited a high proton leak", "high proton leak which", "proton leak which was", "leak which was initiated", "which was initiated upon activation", "was initiated upon activation of", "initiated upon activation of the", "upon activation of the nadph", "activation of the nadph oxidase", "the nadph oxidase and", "nadph oxidase and this", "oxidase and this activation", "and this activation counteracted phagosomal", "this activation counteracted phagosomal acidification", "counteracted phagosomal acidification jankowski", "phagosomal acidification jankowski a", "acidification jankowski a et", "a et al. 2002 .

the", "et al. 2002 .

the reactome", "al. 2002 .

the reactome module", "2002 .

the reactome module describes", ".

the reactome module describes ros", "reactome module describes ros and", "module describes ros and rns", "describes ros and rns production", "ros and rns production by", "and rns production by phagocytic", "rns production by phagocytic cells.", "production by phagocytic cells. the", "by phagocytic cells. the module", "phagocytic cells. the module includes", "cells. the module includes cell", "the module includes cell type", "module includes cell type specific", "includes cell type specific events", "type specific events for", "specific events for example", "example myeloperoxidase mpo", "myeloperoxidase mpo mediated", "mpo mediated production of", "mediated production of hypochlorous acid", "production of hypochlorous acid in", "of hypochlorous acid in neutrophils.", "hypochlorous acid in neutrophils. it", "acid in neutrophils. it also", "in neutrophils. it also highlights", "neutrophils. it also highlights differences", "it also highlights differences between", "also highlights differences between phagosomal", "highlights differences between phagosomal ph", "differences between phagosomal ph dynamics", "between phagosomal ph dynamics in", "phagosomal ph dynamics in neutrophils", "ph dynamics in neutrophils and", "dynamics in neutrophils and macrophages.", "in neutrophils and macrophages. the", "neutrophils and macrophages. the module", "and macrophages. the module describes", "macrophages. the module describes microbicidal", "the module describes microbicidal activity", "module describes microbicidal activity of", "describes microbicidal activity of selective", "microbicidal activity of selective rons", "activity of selective rons such", "of selective rons such as", "selective rons such as hydroxyl", "rons such as hydroxyl radical", "such as hydroxyl radical or", "as hydroxyl radical or peroxynitrite.", "hydroxyl radical or peroxynitrite. however", "or peroxynitrite. however detection", "peroxynitrite. however detection of", "however detection of any", "detection of any of these", "of any of these species", "any of these species in", "of these species in the", "these species in the phagosomal", "species in the phagosomal environment", "in the phagosomal environment is", "the phagosomal environment is subject", "phagosomal environment is subject to", "environment is subject to many", "is subject to many uncertainties", "to many uncertainties n\u00fcsse", "many uncertainties n\u00fcsse o", "uncertainties n\u00fcsse o 2011", "n\u00fcsse o 2011 erard", "o 2011 erard m", "2011 erard m et", "erard m et al. 2018", "m et al. 2018 .", "et al. 2018 . the", "al. 2018 . the mechanisms", "2018 . the mechanisms by", ". the mechanisms by which", "the mechanisms by which reactive", "mechanisms by which reactive oxygen/nitrogen", "by which reactive oxygen/nitrogen species", "which reactive oxygen/nitrogen species kill", "reactive oxygen/nitrogen species kill pathogens", "oxygen/nitrogen species kill pathogens in", "species kill pathogens in phagocytic", "kill pathogens in phagocytic immune", "pathogens in phagocytic immune cells", "in phagocytic immune cells are", "phagocytic immune cells are still", "immune cells are still not", "cells are still not fully", "are still not fully understood." ] }, { "record_id": "GLY_000594_1_28", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1227986", "r hsa", "hsa 1227986", "r hsa 1227986" ] }, { "record_id": "GLY_000594_1_28", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by erbb2", "signaling by erbb2", "also known", "known as", "as her2", "her2 or", "or neu", "is a", "a receptor", "receptor tyrosine", "tyrosine kinase", "belonging to", "to the", "the egfr", "egfr family.", "family. erbb2", "erbb2 possesses", "possesses an", "an extracellular", "extracellular domain", "domain that", "that does", "does not", "not bind", "bind any", "any known", "known ligand", "contrary to", "to other", "other egfr", "egfr family", "family members", "a single", "single transmembrane", "transmembrane domain", "and an", "an intracellular", "intracellular domain", "domain consisting", "consisting of", "of an", "an active", "active kinase", "kinase and", "and a", "a c", "c tail", "tail with", "with multiple", "multiple tyrosine", "tyrosine phosphorylation", "phosphorylation sites.", "sites. inactive", "inactive erbb2", "erbb2 is", "is associated", "associated with", "with a", "a chaperone", "chaperone heat", "heat shock", "shock protein", "protein 90", "and its", "its co", "co chaperone", "chaperone cdc37", "xu et", "et al.", "al. 2001", "citri et", "al. 2004", "al. 2005", "2005 .", ". in", "in addition", "with erbb2ip", "as erbin", "erbin or", "or lap2", "a protein", "protein responsible", "responsible for", "for proper", "proper localization", "localization of", "of erbb2.", "erbb2. in", "in epithelial", "epithelial cells", "erbb2ip restricts", "restricts expression", "expression of", "of erbb2", "erbb2 to", "to basolateral", "basolateral plasma", "plasma membrane", "membrane regions", "borg et", "al. 2000", "2000 .

", ".

erbb2", "erbb2 becomes", "becomes activated", "activated by", "by forming", "forming a", "a heterodimer", "heterodimer with", "with another", "another ligand", "ligand activated", "activated egfr", "family member", "either egfr", "erbb3 or", "or erbb4", "which is", "is accompanied", "accompanied by", "by dissociation", "dissociation of", "of chaperoning", "chaperoning proteins", "proteins hsp90", "hsp90 and", "and cdc37", "as well", "well as", "as erbb2ip", "from erbb2.", "erbb2. erbb2", "erbb2 heterodimers", "heterodimers function", "function to", "to promote", "promote cell", "cell proliferation", "cell survival", "survival and", "and differentiation", "depending on", "on the", "the cellular", "cellular context.", "context. erbb2", "erbb2 can", "can also", "also be", "be activated", "by homodimerization", "homodimerization when", "when it", "it is", "is overexpressed", "in cancer", "cancer for", "for example.", "example.

", "

in", "in cells", "cells expressing", "expressing both", "both erbb2", "erbb2 and", "and egfr", "egf stimulation", "stimulation of", "of egfr", "egfr leads", "leads to", "to formation", "formation of", "of both", "both erbb2:egfr", "erbb2:egfr heterodimers", "wada et", "al. 1990", "karunagaran et", "al. 1996", "egfr homodimers.", "homodimers. heterodimers", "heterodimers of", "egfr trans", "trans autophosphorylate", "autophosphorylate on", "on twelve", "twelve tyrosine", "tyrosine residues", "six in", "in the", "the c", "tail of", "egfr and", "and six", "y1222 and", "and y1248", "margolis et", "al. 1989", "hazan et", "1990 walton", "walton et", "helin et", "al. 1991", "ricci et", "al. 1995", "pinkas kramarski", "kramarski 1996", "1996 .", ". phosphorylated", "phosphorylated tyrosine", "residues in", "and erbb2", "erbb2 serve", "serve as", "as docking", "docking sites", "sites for", "for downstream", "downstream signaling", "signaling molecules.", "molecules. three", "three key", "key signaling", "signaling pathways", "pathways activated", "by erbb2:egfr", "heterodimers are", "are raf/map", "raf/map kinase", "kinase cascade", "pi3k induced", "induced akt", "akt signaling", "and signaling", "by phospholipase", "phospholipase c", "c gamma", "plcg1 .", ". downregulation", "downregulation of", "egfr signaling", "signaling is", "is mediated", "mediated by", "by ubiquitin", "ubiquitin ligase", "ligase cbl", "and is", "is shown", "shown under", "under signaling", "by egfr.

", "egfr.

in", "expressing erbb2", "and erbb3", "erbb3 activated", "by neuregulin", "neuregulin nrg1", "nrg1 or", "or nrg2", "nrg2 binding", "tzahar et", "al. 1994", "forms a", "with erbb2", "kramarski et", "2004 .", ". erbb3", "erbb3 is", "is the", "the only", "only egfr", "member with", "with no", "no kinase", "kinase activity", "and can", "can only", "only function", "function in", "in heterodimers", "erbb2 being", "being its", "its preferred", "preferred heterodimerization", "heterodimerization partner.", "partner. after", "after heterodimerization", "erbb2 phosphorylates", "phosphorylates ten", "ten tyrosine", "of erbb3", "y1289 and", "and y1328", "prigent et", "vijapurkar et", "al. 2003", "li et", "al. 2007", "that subsequently", "subsequently serve", "signaling molecules", "resulting in", "in activation", "activation of", "of pi3k", "signaling and", "and raf/map", "kinase cascade.", "cascade. signaling", "by erbb3", "is downregulated", "downregulated by", "by the", "the action", "action of", "of rnf41", "rnf41 ubiquitin", "as nrdp1.", "nrdp1.

", "and erbb4", "ligand stimulated", "stimulated erbb4", "erbb4 can", "can either", "either homodimerize", "homodimerize or", "or form", "form heterodimers", "heterodimers with", "in trans", "trans autophosphorylation", "autophosphorylation of", "erbb4 on", "on c", "tail tyrosine", "residues that", "that will", "will subsequently", "leading to", "to activation", "of raf/map", "cascade and", "the case", "case of", "of erbb4", "erbb4 cyt1", "cyt1 isoforms", "cohen et", "kaushansky et", "al. 2008", "2008 .", ". signaling", "by erbb4", "erbb4 is", "of wwp1", "wwp1 and", "and itch", "itch ubiquitin", "ubiquitin ligases", "by erbb4.", "erbb2 also", "also known as", "known as her2", "as her2 or", "her2 or neu", "neu is", "is a receptor", "a receptor tyrosine", "receptor tyrosine kinase", "kinase rtk", "rtk belonging", "belonging to the", "to the egfr", "the egfr family.", "egfr family. erbb2", "family. erbb2 possesses", "erbb2 possesses an", "possesses an extracellular", "an extracellular domain", "extracellular domain that", "domain that does", "that does not", "does not bind", "not bind any", "bind any known", "any known ligand", "ligand contrary", "contrary to other", "to other egfr", "other egfr family", "egfr family members", "members a", "a single transmembrane", "single transmembrane domain", "domain and", "and an intracellular", "an intracellular domain", "intracellular domain consisting", "domain consisting of", "consisting of an", "of an active", "an active kinase", "active kinase and", "kinase and a", "and a c", "a c tail", "c tail with", "tail with multiple", "with multiple tyrosine", "multiple tyrosine phosphorylation", "tyrosine phosphorylation sites.", "phosphorylation sites. inactive", "sites. inactive erbb2", "inactive erbb2 is", "erbb2 is associated", "is associated with", "associated with a", "with a chaperone", "a chaperone heat", "chaperone heat shock", "heat shock protein", "shock protein 90", "90 hsp90", "and its co", "its co chaperone", "co chaperone cdc37", "cdc37 xu", "xu et al.", "et al. 2001", "2001 citri", "citri et al.", "et al. 2004", "2004 xu", "et al. 2005", "al. 2005 .", "2005 . in", ". in addition", "addition erbb2", "associated with erbb2ip", "erbb2ip also", "known as erbin", "as erbin or", "erbin or lap2", "a protein responsible", "protein responsible for", "responsible for proper", "for proper localization", "proper localization of", "localization of erbb2.", "of erbb2. in", "erbb2. in epithelial", "in epithelial cells", "cells erbb2ip", "erbb2ip restricts expression", "restricts expression of", "expression of erbb2", "of erbb2 to", "erbb2 to basolateral", "to basolateral plasma", "basolateral plasma membrane", "plasma membrane regions", "regions borg", "borg et al.", "et al. 2000", "al. 2000 .

", "2000 .

erbb2", ".

erbb2 becomes", "erbb2 becomes activated", "becomes activated by", "activated by forming", "by forming a", "forming a heterodimer", "a heterodimer with", "heterodimer with another", "with another ligand", "another ligand activated", "ligand activated egfr", "activated egfr family", "egfr family member", "member either", "egfr erbb3", "erbb3 or erbb4", "erbb4 which", "which is accompanied", "is accompanied by", "accompanied by dissociation", "by dissociation of", "dissociation of chaperoning", "of chaperoning proteins", "chaperoning proteins hsp90", "proteins hsp90 and", "hsp90 and cdc37", "cdc37 citri", "as well as", "well as erbb2ip", "erbb2ip borg", "2000 from", "from erbb2. erbb2", "erbb2. erbb2 heterodimers", "erbb2 heterodimers function", "heterodimers function to", "function to promote", "to promote cell", "promote cell proliferation", "proliferation cell", "cell survival and", "survival and differentiation", "differentiation depending", "depending on the", "on the cellular", "the cellular context.", "cellular context. erbb2", "context. erbb2 can", "erbb2 can also", "can also be", "also be activated", "be activated by", "activated by homodimerization", "by homodimerization when", "homodimerization when it", "when it is", "it is overexpressed", "overexpressed in", "in cancer for", "cancer for example.", "for example.

", "example.

in", "

in cells", "in cells expressing", "cells expressing both", "expressing both erbb2", "both erbb2 and", "erbb2 and egfr", "egfr egf", "egf stimulation of", "stimulation of egfr", "of egfr leads", "egfr leads to", "leads to formation", "to formation of", "formation of both", "of both erbb2:egfr", "both erbb2:egfr heterodimers", "heterodimers wada", "wada et al.", "et al. 1990", "1990 karunagaran", "karunagaran et al.", "et al. 1996", "1996 and", "and egfr homodimers.", "egfr homodimers. heterodimers", "homodimers. heterodimers of", "heterodimers of erbb2", "of erbb2 and", "and egfr trans", "egfr trans autophosphorylate", "trans autophosphorylate on", "autophosphorylate on twelve", "on twelve tyrosine", "twelve tyrosine residues", "residues six", "six in the", "in the c", "the c tail", "c tail of", "tail of egfr", "of egfr and", "egfr and six", "and six in", "tail of erbb2", "y1023 y1139", "y1139 y1196", "y1196 y1221", "y1221 y1222", "y1222 and y1248", "y1248 margolis", "margolis et al.", "et al. 1989", "1989 hazan", "hazan et al.", "al. 1990 walton", "1990 walton et", "1990 helin", "helin et al.", "et al. 1991", "1991 ricci", "ricci et al.", "et al. 1995", "1995 pinkas", "pinkas kramarski 1996", "kramarski 1996 .", "1996 . phosphorylated", ". phosphorylated tyrosine", "phosphorylated tyrosine residues", "tyrosine residues in", "residues in the", "egfr and erbb2", "and erbb2 serve", "erbb2 serve as", "serve as docking", "as docking sites", "docking sites for", "sites for downstream", "for downstream signaling", "downstream signaling molecules.", "signaling molecules. three", "molecules. three key", "three key signaling", "key signaling pathways", "signaling pathways activated", "pathways activated by", "activated by erbb2:egfr", "by erbb2:egfr heterodimers", "erbb2:egfr heterodimers are", "heterodimers are raf/map", "are raf/map kinase", "raf/map kinase cascade", "cascade pi3k", "pi3k induced akt", "induced akt signaling", "and signaling by", "signaling by phospholipase", "by phospholipase c", "phospholipase c gamma", "gamma plcg1", "plcg1 . downregulation", ". downregulation of", "downregulation of egfr", "of egfr signaling", "egfr signaling is", "signaling is mediated", "is mediated by", "mediated by ubiquitin", "by ubiquitin ligase", "ubiquitin ligase cbl", "cbl and", "and is shown", "is shown under", "shown under signaling", "under signaling by", "signaling by egfr.

", "by egfr.

in", "egfr.

in cells", "cells expressing erbb2", "expressing erbb2 and", "erbb2 and erbb3", "erbb3 erbb3", "erbb3 activated by", "activated by neuregulin", "by neuregulin nrg1", "neuregulin nrg1 or", "nrg1 or nrg2", "or nrg2 binding", "binding tzahar", "tzahar et al.", "et al. 1994", "1994 forms", "forms a heterodimer", "heterodimer with erbb2", "erbb2 pinkas", "pinkas kramarski et", "kramarski et al.", "1996 citri", "al. 2004 .", "2004 . erbb3", ". erbb3 is", "erbb3 is the", "is the only", "the only egfr", "only egfr family", "family member with", "member with no", "with no kinase", "no kinase activity", "activity and", "and can only", "can only function", "only function in", "function in heterodimers", "with erbb2 being", "erbb2 being its", "being its preferred", "its preferred heterodimerization", "preferred heterodimerization partner.", "heterodimerization partner. after", "partner. after heterodimerization", "heterodimerization erbb2", "erbb2 phosphorylates ten", "phosphorylates ten tyrosine", "ten tyrosine residues", "tail of erbb3", "erbb3 y1054", "y1054 y1197", "y1197 y1199", "y1199 y1222", "y1222 y1224", "y1224 y1260", "y1260 y1262", "y1262 y1276", "y1276 y1289", "y1289 and y1328", "y1328 prigent", "prigent et al.", "1994 pinkas", "1996 vijapurkar", "vijapurkar et al.", "et al. 2003", "2003 li", "li et al.", "et al. 2007", "2007 that", "that subsequently serve", "subsequently serve as", "downstream signaling molecules", "molecules resulting", "resulting in activation", "in activation of", "activation of pi3k", "of pi3k induced", "akt signaling and", "signaling and raf/map", "and raf/map kinase", "raf/map kinase cascade.", "kinase cascade. signaling", "cascade. signaling by", "signaling by erbb3", "by erbb3 is", "erbb3 is downregulated", "is downregulated by", "downregulated by the", "by the action", "the action of", "action of rnf41", "of rnf41 ubiquitin", "rnf41 ubiquitin ligase", "ligase also", "known as nrdp1.", "as nrdp1.

", "nrdp1.

in", "erbb2 and erbb4", "erbb4 ligand", "ligand stimulated erbb4", "stimulated erbb4 can", "erbb4 can either", "can either homodimerize", "either homodimerize or", "homodimerize or form", "or form heterodimers", "form heterodimers with", "heterodimers with erbb2", "erbb2 li", "resulting in trans", "in trans autophosphorylation", "trans autophosphorylation of", "autophosphorylation of erbb2", "and erbb4 on", "erbb4 on c", "on c tail", "c tail tyrosine", "tail tyrosine residues", "tyrosine residues that", "residues that will", "that will subsequently", "will subsequently serve", "molecules leading", "leading to activation", "to activation of", "activation of raf/map", "of raf/map kinase", "kinase cascade and", "and in", "in the case", "the case of", "case of erbb4", "of erbb4 cyt1", "erbb4 cyt1 isoforms", "isoforms pi3k", "signaling hazan", "1990 cohen", "cohen et al.", "1996 li", "2007 kaushansky", "kaushansky et al.", "et al. 2008", "al. 2008 .", "2008 . signaling", ". signaling by", "signaling by erbb4", "by erbb4 is", "erbb4 is downregulated", "action of wwp1", "of wwp1 and", "wwp1 and itch", "and itch ubiquitin", "itch ubiquitin ligases", "ligases and", "signaling by erbb4.", "erbb2 also known", "also known as her2", "known as her2 or", "as her2 or neu", "or neu is", "neu is a", "is a receptor tyrosine", "a receptor tyrosine kinase", "tyrosine kinase rtk", "rtk belonging to", "belonging to the egfr", "to the egfr family.", "the egfr family. erbb2", "egfr family. erbb2 possesses", "family. erbb2 possesses an", "erbb2 possesses an extracellular", "possesses an extracellular domain", "an extracellular domain that", "extracellular domain that does", "domain that does not", "that does not bind", "does not bind any", "not bind any known", "bind any known ligand", "known ligand contrary", "ligand contrary to", "contrary to other egfr", "to other egfr family", "other egfr family members", "family members a", "members a single", "a single transmembrane domain", "transmembrane domain and", "domain and an", "and an intracellular domain", "an intracellular domain consisting", "intracellular domain consisting of", "domain consisting of an", "consisting of an active", "of an active kinase", "an active kinase and", "active kinase and a", "kinase and a c", "and a c tail", "a c tail with", "c tail with multiple", "tail with multiple tyrosine", "with multiple tyrosine phosphorylation", "multiple tyrosine phosphorylation sites.", "tyrosine phosphorylation sites. inactive", "phosphorylation sites. inactive erbb2", "sites. inactive erbb2 is", "inactive erbb2 is associated", "erbb2 is associated with", "is associated with a", "associated with a chaperone", "with a chaperone heat", "a chaperone heat shock", "chaperone heat shock protein", "heat shock protein 90", "protein 90 hsp90", "hsp90 and its", "and its co chaperone", "its co chaperone cdc37", "chaperone cdc37 xu", "cdc37 xu et", "xu et al. 2001", "al. 2001 citri", "2001 citri et", "citri et al. 2004", "al. 2004 xu", "2004 xu et", "xu et al. 2005", "et al. 2005 .", "al. 2005 . in", "2005 . in addition", "in addition erbb2", "addition erbb2 is", "is associated with erbb2ip", "with erbb2ip also", "erbb2ip also known", "also known as erbin", "known as erbin or", "as erbin or lap2", "lap2 a", "a protein responsible for", "protein responsible for proper", "responsible for proper localization", "for proper localization of", "proper localization of erbb2.", "localization of erbb2. in", "of erbb2. in epithelial", "erbb2. in epithelial cells", "epithelial cells erbb2ip", "cells erbb2ip restricts", "erbb2ip restricts expression of", "restricts expression of erbb2", "expression of erbb2 to", "of erbb2 to basolateral", "erbb2 to basolateral plasma", "to basolateral plasma membrane", "basolateral plasma membrane regions", "membrane regions borg", "regions borg et", "borg et al. 2000", "et al. 2000 .

", "al. 2000 .

erbb2", "2000 .

erbb2 becomes", ".

erbb2 becomes activated", "erbb2 becomes activated by", "becomes activated by forming", "activated by forming a", "by forming a heterodimer", "forming a heterodimer with", "a heterodimer with another", "heterodimer with another ligand", "with another ligand activated", "another ligand activated egfr", "ligand activated egfr family", "activated egfr family member", "family member either", "member either egfr", "either egfr erbb3", "egfr erbb3 or", "or erbb4 which", "erbb4 which is", "which is accompanied by", "is accompanied by dissociation", "accompanied by dissociation of", "by dissociation of chaperoning", "dissociation of chaperoning proteins", "of chaperoning proteins hsp90", "chaperoning proteins hsp90 and", "proteins hsp90 and cdc37", "and cdc37 citri", "cdc37 citri et", "2004 as", "as well as erbb2ip", "as erbb2ip borg", "erbb2ip borg et", "al. 2000 from", "2000 from erbb2.", "from erbb2. erbb2 heterodimers", "erbb2. erbb2 heterodimers function", "erbb2 heterodimers function to", "heterodimers function to promote", "function to promote cell", "to promote cell proliferation", "cell proliferation cell", "proliferation cell survival", "cell survival and differentiation", "and differentiation depending", "differentiation depending on", "depending on the cellular", "on the cellular context.", "the cellular context. erbb2", "cellular context. erbb2 can", "context. erbb2 can also", "erbb2 can also be", "can also be activated", "also be activated by", "be activated by homodimerization", "activated by homodimerization when", "by homodimerization when it", "homodimerization when it is", "when it is overexpressed", "is overexpressed in", "overexpressed in cancer", "in cancer for example.", "cancer for example.

", "for example.

in", "example.

in cells", "

in cells expressing", "in cells expressing both", "cells expressing both erbb2", "expressing both erbb2 and", "both erbb2 and egfr", "and egfr egf", "egfr egf stimulation", "egf stimulation of egfr", "stimulation of egfr leads", "of egfr leads to", "egfr leads to formation", "leads to formation of", "to formation of both", "formation of both erbb2:egfr", "of both erbb2:egfr heterodimers", "erbb2:egfr heterodimers wada", "heterodimers wada et", "wada et al. 1990", "al. 1990 karunagaran", "1990 karunagaran et", "karunagaran et al. 1996", "al. 1996 and", "1996 and egfr", "and egfr homodimers. heterodimers", "egfr homodimers. heterodimers of", "homodimers. heterodimers of erbb2", "heterodimers of erbb2 and", "of erbb2 and egfr", "erbb2 and egfr trans", "and egfr trans autophosphorylate", "egfr trans autophosphorylate on", "trans autophosphorylate on twelve", "autophosphorylate on twelve tyrosine", "on twelve tyrosine residues", "tyrosine residues six", "residues six in", "six in the c", "in the c tail", "the c tail of", "c tail of egfr", "tail of egfr and", "of egfr and six", "egfr and six in", "and six in the", "c tail of erbb2", "erbb2 y1023", "y1221 y1222 and", "and y1248 margolis", "y1248 margolis et", "margolis et al. 1989", "al. 1989 hazan", "1989 hazan et", "hazan et al. 1990", "et al. 1990 walton", "al. 1990 walton et", "walton et al.", "al. 1990 helin", "1990 helin et", "helin et al. 1991", "al. 1991 ricci", "1991 ricci et", "ricci et al. 1995", "al. 1995 pinkas", "1995 pinkas kramarski", "pinkas kramarski 1996 .", "kramarski 1996 . phosphorylated", "1996 . phosphorylated tyrosine", ". phosphorylated tyrosine residues", "phosphorylated tyrosine residues in", "tyrosine residues in the", "residues in the c", "of egfr and erbb2", "egfr and erbb2 serve", "and erbb2 serve as", "erbb2 serve as docking", "serve as docking sites", "as docking sites for", "docking sites for downstream", "sites for downstream signaling", "for downstream signaling molecules.", "downstream signaling molecules. three", "signaling molecules. three key", "molecules. three key signaling", "three key signaling pathways", "key signaling pathways activated", "signaling pathways activated by", "pathways activated by erbb2:egfr", "activated by erbb2:egfr heterodimers", "by erbb2:egfr heterodimers are", "erbb2:egfr heterodimers are raf/map", "heterodimers are raf/map kinase", "are raf/map kinase cascade", "kinase cascade pi3k", "cascade pi3k induced", "pi3k induced akt signaling", "signaling and signaling", "and signaling by phospholipase", "signaling by phospholipase c", "by phospholipase c gamma", "c gamma plcg1", "gamma plcg1 .", "plcg1 . downregulation of", ". downregulation of egfr", "downregulation of egfr signaling", "of egfr signaling is", "egfr signaling is mediated", "signaling is mediated by", "is mediated by ubiquitin", "mediated by ubiquitin ligase", "by ubiquitin ligase cbl", "ligase cbl and", "cbl and is", "and is shown under", "is shown under signaling", "shown under signaling by", "under signaling by egfr.

", "signaling by egfr.

in", "by egfr.

in cells", "egfr.

in cells expressing", "in cells expressing erbb2", "cells expressing erbb2 and", "expressing erbb2 and erbb3", "and erbb3 erbb3", "erbb3 erbb3 activated", "erbb3 activated by neuregulin", "activated by neuregulin nrg1", "by neuregulin nrg1 or", "neuregulin nrg1 or nrg2", "nrg1 or nrg2 binding", "nrg2 binding tzahar", "binding tzahar et", "tzahar et al. 1994", "al. 1994 forms", "1994 forms a", "forms a heterodimer with", "a heterodimer with erbb2", "with erbb2 pinkas", "erbb2 pinkas kramarski", "pinkas kramarski et al.", "kramarski et al. 1996", "al. 1996 citri", "1996 citri et", "et al. 2004 .", "al. 2004 . erbb3", "2004 . erbb3 is", ". erbb3 is the", "erbb3 is the only", "is the only egfr", "the only egfr family", "only egfr family member", "egfr family member with", "family member with no", "member with no kinase", "with no kinase activity", "kinase activity and", "activity and can", "and can only function", "can only function in", "only function in heterodimers", "in heterodimers with", "with erbb2 being its", "erbb2 being its preferred", "being its preferred heterodimerization", "its preferred heterodimerization partner.", "preferred heterodimerization partner. after", "heterodimerization partner. after heterodimerization", "after heterodimerization erbb2", "heterodimerization erbb2 phosphorylates", "erbb2 phosphorylates ten tyrosine", "phosphorylates ten tyrosine residues", "ten tyrosine residues in", "c tail of erbb3", "of erbb3 y1054", "y1276 y1289 and", "and y1328 prigent", "y1328 prigent et", "prigent et al. 1994", "al. 1994 pinkas", "1994 pinkas kramarski", "al. 1996 vijapurkar", "1996 vijapurkar et", "vijapurkar et al. 2003", "al. 2003 li", "2003 li et", "li et al. 2007", "al. 2007 that", "2007 that subsequently", "that subsequently serve as", "subsequently serve as docking", "for downstream signaling molecules", "signaling molecules resulting", "molecules resulting in", "resulting in activation of", "in activation of pi3k", "activation of pi3k induced", "of pi3k induced akt", "induced akt signaling and", "akt signaling and raf/map", "signaling and raf/map kinase", "and raf/map kinase cascade.", "raf/map kinase cascade. signaling", "kinase cascade. signaling by", "cascade. signaling by erbb3", "signaling by erbb3 is", "by erbb3 is downregulated", "erbb3 is downregulated by", "is downregulated by the", "downregulated by the action", "by the action of", "the action of rnf41", "action of rnf41 ubiquitin", "of rnf41 ubiquitin ligase", "ubiquitin ligase also", "ligase also known", "also known as nrdp1.", "known as nrdp1.

", "as nrdp1.

in", "nrdp1.

in cells", "expressing erbb2 and erbb4", "and erbb4 ligand", "erbb4 ligand stimulated", "ligand stimulated erbb4 can", "stimulated erbb4 can either", "erbb4 can either homodimerize", "can either homodimerize or", "either homodimerize or form", "homodimerize or form heterodimers", "or form heterodimers with", "form heterodimers with erbb2", "with erbb2 li", "erbb2 li et", "2007 resulting", "resulting in trans autophosphorylation", "in trans autophosphorylation of", "trans autophosphorylation of erbb2", "autophosphorylation of erbb2 and", "of erbb2 and erbb4", "erbb2 and erbb4 on", "and erbb4 on c", "erbb4 on c tail", "on c tail tyrosine", "c tail tyrosine residues", "tail tyrosine residues that", "tyrosine residues that will", "residues that will subsequently", "that will subsequently serve", "will subsequently serve as", "signaling molecules leading", "molecules leading to", "leading to activation of", "to activation of raf/map", "activation of raf/map kinase", "of raf/map kinase cascade", "raf/map kinase cascade and", "cascade and in", "and in the", "in the case of", "the case of erbb4", "case of erbb4 cyt1", "of erbb4 cyt1 isoforms", "cyt1 isoforms pi3k", "isoforms pi3k induced", "akt signaling hazan", "signaling hazan et", "al. 1990 cohen", "1990 cohen et", "cohen et al. 1996", "al. 1996 li", "1996 li et", "al. 2007 kaushansky", "2007 kaushansky et", "kaushansky et al. 2008", "et al. 2008 .", "al. 2008 . signaling", "2008 . signaling by", ". signaling by erbb4", "signaling by erbb4 is", "by erbb4 is downregulated", "erbb4 is downregulated by", "the action of wwp1", "action of wwp1 and", "of wwp1 and itch", "wwp1 and itch ubiquitin", "and itch ubiquitin ligases", "ubiquitin ligases and", "ligases and is", "under signaling by erbb4.", "erbb2 also known as", "also known as her2 or", "known as her2 or neu", "her2 or neu is", "or neu is a", "neu is a receptor", "is a receptor tyrosine kinase", "receptor tyrosine kinase rtk", "kinase rtk belonging", "rtk belonging to the", "belonging to the egfr family.", "to the egfr family. erbb2", "the egfr family. erbb2 possesses", "egfr family. erbb2 possesses an", "family. erbb2 possesses an extracellular", "erbb2 possesses an extracellular domain", "possesses an extracellular domain that", "an extracellular domain that does", "extracellular domain that does not", "domain that does not bind", "that does not bind any", "does not bind any known", "not bind any known ligand", "any known ligand contrary", "known ligand contrary to", "ligand contrary to other", "contrary to other egfr family", "to other egfr family members", "egfr family members a", "family members a single", "members a single transmembrane", "single transmembrane domain and", "transmembrane domain and an", "domain and an intracellular", "and an intracellular domain consisting", "an intracellular domain consisting of", "intracellular domain consisting of an", "domain consisting of an active", "consisting of an active kinase", "of an active kinase and", "an active kinase and a", "active kinase and a c", "kinase and a c tail", "and a c tail with", "a c tail with multiple", "c tail with multiple tyrosine", "tail with multiple tyrosine phosphorylation", "with multiple tyrosine phosphorylation sites.", "multiple tyrosine phosphorylation sites. inactive", "tyrosine phosphorylation sites. inactive erbb2", "phosphorylation sites. inactive erbb2 is", "sites. inactive erbb2 is associated", "inactive erbb2 is associated with", "erbb2 is associated with a", "is associated with a chaperone", "associated with a chaperone heat", "with a chaperone heat shock", "a chaperone heat shock protein", "chaperone heat shock protein 90", "shock protein 90 hsp90", "90 hsp90 and", "hsp90 and its co", "and its co chaperone cdc37", "co chaperone cdc37 xu", "chaperone cdc37 xu et", "cdc37 xu et al.", "et al. 2001 citri", "al. 2001 citri et", "2001 citri et al.", "et al. 2004 xu", "al. 2004 xu et", "2004 xu et al.", "xu et al. 2005 .", "et al. 2005 . in", "al. 2005 . in addition", ". in addition erbb2", "in addition erbb2 is", "addition erbb2 is associated", "erbb2 is associated with erbb2ip", "associated with erbb2ip also", "with erbb2ip also known", "erbb2ip also known as", "also known as erbin or", "known as erbin or lap2", "or lap2 a", "lap2 a protein", "a protein responsible for proper", "protein responsible for proper localization", "responsible for proper localization of", "for proper localization of erbb2.", "proper localization of erbb2. in", "localization of erbb2. in epithelial", "of erbb2. in epithelial cells", "in epithelial cells erbb2ip", "epithelial cells erbb2ip restricts", "cells erbb2ip restricts expression", "erbb2ip restricts expression of erbb2", "restricts expression of erbb2 to", "expression of erbb2 to basolateral", "of erbb2 to basolateral plasma", "erbb2 to basolateral plasma membrane", "to basolateral plasma membrane regions", "plasma membrane regions borg", "membrane regions borg et", "regions borg et al.", "borg et al. 2000 .

", "et al. 2000 .

erbb2", "al. 2000 .

erbb2 becomes", "2000 .

erbb2 becomes activated", ".

erbb2 becomes activated by", "erbb2 becomes activated by forming", "becomes activated by forming a", "activated by forming a heterodimer", "by forming a heterodimer with", "forming a heterodimer with another", "a heterodimer with another ligand", "heterodimer with another ligand activated", "with another ligand activated egfr", "another ligand activated egfr family", "ligand activated egfr family member", "egfr family member either", "family member either egfr", "either egfr erbb3 or", "egfr erbb3 or erbb4", "erbb3 or erbb4 which", "or erbb4 which is", "erbb4 which is accompanied", "which is accompanied by dissociation", "is accompanied by dissociation of", "accompanied by dissociation of chaperoning", "by dissociation of chaperoning proteins", "dissociation of chaperoning proteins hsp90", "of chaperoning proteins hsp90 and", "chaperoning proteins hsp90 and cdc37", "hsp90 and cdc37 citri", "and cdc37 citri et", "cdc37 citri et al.", "al. 2004 as", "2004 as well", "well as erbb2ip borg", "as erbb2ip borg et", "erbb2ip borg et al.", "et al. 2000 from", "al. 2000 from erbb2.", "2000 from erbb2. erbb2", "from erbb2. erbb2 heterodimers function", "erbb2. erbb2 heterodimers function to", "erbb2 heterodimers function to promote", "heterodimers function to promote cell", "function to promote cell proliferation", "promote cell proliferation cell", "cell proliferation cell survival", "proliferation cell survival and", "survival and differentiation depending", "and differentiation depending on", "differentiation depending on the", "depending on the cellular context.", "on the cellular context. erbb2", "the cellular context. erbb2 can", "cellular context. erbb2 can also", "context. erbb2 can also be", "erbb2 can also be activated", "can also be activated by", "also be activated by homodimerization", "be activated by homodimerization when", "activated by homodimerization when it", "by homodimerization when it is", "homodimerization when it is overexpressed", "it is overexpressed in", "is overexpressed in cancer", "overexpressed in cancer for", "in cancer for example.

", "cancer for example.

in", "for example.

in cells", "example.

in cells expressing", "

in cells expressing both", "in cells expressing both erbb2", "cells expressing both erbb2 and", "expressing both erbb2 and egfr", "erbb2 and egfr egf", "and egfr egf stimulation", "egfr egf stimulation of", "egf stimulation of egfr leads", "stimulation of egfr leads to", "of egfr leads to formation", "egfr leads to formation of", "leads to formation of both", "to formation of both erbb2:egfr", "formation of both erbb2:egfr heterodimers", "both erbb2:egfr heterodimers wada", "erbb2:egfr heterodimers wada et", "heterodimers wada et al.", "et al. 1990 karunagaran", "al. 1990 karunagaran et", "1990 karunagaran et al.", "et al. 1996 and", "al. 1996 and egfr", "1996 and egfr homodimers.", "and egfr homodimers. heterodimers of", "egfr homodimers. heterodimers of erbb2", "homodimers. heterodimers of erbb2 and", "heterodimers of erbb2 and egfr", "of erbb2 and egfr trans", "erbb2 and egfr trans autophosphorylate", "and egfr trans autophosphorylate on", "egfr trans autophosphorylate on twelve", "trans autophosphorylate on twelve tyrosine", "autophosphorylate on twelve tyrosine residues", "twelve tyrosine residues six", "tyrosine residues six in", "residues six in the", "six in the c tail", "in the c tail of", "the c tail of egfr", "c tail of egfr and", "tail of egfr and six", "of egfr and six in", "egfr and six in the", "and six in the c", "the c tail of erbb2", "of erbb2 y1023", "y1023 y1139 y1196", "y1139 y1196 y1221", "y1196 y1221 y1222", "y1221 y1222 and y1248", "y1222 and y1248 margolis", "and y1248 margolis et", "y1248 margolis et al.", "et al. 1989 hazan", "al. 1989 hazan et", "1989 hazan et al.", "hazan et al. 1990 walton", "et al. 1990 walton et", "1990 walton et al.", "walton et al. 1990", "al. 1990 helin et", "1990 helin et al.", "et al. 1991 ricci", "al. 1991 ricci et", "1991 ricci et al.", "et al. 1995 pinkas", "al. 1995 pinkas kramarski", "1995 pinkas kramarski 1996", "pinkas kramarski 1996 . phosphorylated", "kramarski 1996 . phosphorylated tyrosine", "1996 . phosphorylated tyrosine residues", ". phosphorylated tyrosine residues in", "phosphorylated tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "tail of egfr and erbb2", "of egfr and erbb2 serve", "egfr and erbb2 serve as", "and erbb2 serve as docking", "erbb2 serve as docking sites", "serve as docking sites for", "as docking sites for downstream", "docking sites for downstream signaling", "sites for downstream signaling molecules.", "for downstream signaling molecules. three", "downstream signaling molecules. three key", "signaling molecules. three key signaling", "molecules. three key signaling pathways", "three key signaling pathways activated", "key signaling pathways activated by", "signaling pathways activated by erbb2:egfr", "pathways activated by erbb2:egfr heterodimers", "activated by erbb2:egfr heterodimers are", "by erbb2:egfr heterodimers are raf/map", "erbb2:egfr heterodimers are raf/map kinase", "heterodimers are raf/map kinase cascade", "raf/map kinase cascade pi3k", "kinase cascade pi3k induced", "cascade pi3k induced akt", "akt signaling and signaling", "signaling and signaling by", "and signaling by phospholipase c", "signaling by phospholipase c gamma", "phospholipase c gamma plcg1", "c gamma plcg1 .", "gamma plcg1 . downregulation", "plcg1 . downregulation of egfr", ". downregulation of egfr signaling", "downregulation of egfr signaling is", "of egfr signaling is mediated", "egfr signaling is mediated by", "signaling is mediated by ubiquitin", "is mediated by ubiquitin ligase", "mediated by ubiquitin ligase cbl", "ubiquitin ligase cbl and", "ligase cbl and is", "cbl and is shown", "and is shown under signaling", "is shown under signaling by", "shown under signaling by egfr.

", "under signaling by egfr.

in", "signaling by egfr.

in cells", "by egfr.

in cells expressing", "egfr.

in cells expressing erbb2", "in cells expressing erbb2 and", "cells expressing erbb2 and erbb3", "erbb2 and erbb3 erbb3", "and erbb3 erbb3 activated", "erbb3 erbb3 activated by", "erbb3 activated by neuregulin nrg1", "activated by neuregulin nrg1 or", "by neuregulin nrg1 or nrg2", "neuregulin nrg1 or nrg2 binding", "or nrg2 binding tzahar", "nrg2 binding tzahar et", "binding tzahar et al.", "et al. 1994 forms", "al. 1994 forms a", "1994 forms a heterodimer", "forms a heterodimer with erbb2", "heterodimer with erbb2 pinkas", "with erbb2 pinkas kramarski", "erbb2 pinkas kramarski et", "pinkas kramarski et al. 1996", "et al. 1996 citri", "al. 1996 citri et", "1996 citri et al.", "citri et al. 2004 .", "et al. 2004 . erbb3", "al. 2004 . erbb3 is", "2004 . erbb3 is the", ". erbb3 is the only", "erbb3 is the only egfr", "is the only egfr family", "the only egfr family member", "only egfr family member with", "egfr family member with no", "family member with no kinase", "member with no kinase activity", "no kinase activity and", "kinase activity and can", "activity and can only", "and can only function in", "can only function in heterodimers", "function in heterodimers with", "in heterodimers with erbb2", "heterodimers with erbb2 being", "with erbb2 being its preferred", "erbb2 being its preferred heterodimerization", "being its preferred heterodimerization partner.", "its preferred heterodimerization partner. after", "preferred heterodimerization partner. after heterodimerization", "partner. after heterodimerization erbb2", "after heterodimerization erbb2 phosphorylates", "heterodimerization erbb2 phosphorylates ten", "erbb2 phosphorylates ten tyrosine residues", "phosphorylates ten tyrosine residues in", "ten tyrosine residues in the", "the c tail of erbb3", "tail of erbb3 y1054", "erbb3 y1054 y1197", "y1054 y1197 y1199", "y1197 y1199 y1222", "y1199 y1222 y1224", "y1222 y1224 y1260", "y1224 y1260 y1262", "y1260 y1262 y1276", "y1262 y1276 y1289", "y1276 y1289 and y1328", "y1289 and y1328 prigent", "and y1328 prigent et", "y1328 prigent et al.", "et al. 1994 pinkas", "al. 1994 pinkas kramarski", "1994 pinkas kramarski et", "et al. 1996 vijapurkar", "al. 1996 vijapurkar et", "1996 vijapurkar et al.", "et al. 2003 li", "al. 2003 li et", "2003 li et al.", "et al. 2007 that", "al. 2007 that subsequently", "2007 that subsequently serve", "that subsequently serve as docking", "subsequently serve as docking sites", "sites for downstream signaling molecules", "downstream signaling molecules resulting", "signaling molecules resulting in", "molecules resulting in activation", "resulting in activation of pi3k", "in activation of pi3k induced", "activation of pi3k induced akt", "of pi3k induced akt signaling", "pi3k induced akt signaling and", "induced akt signaling and raf/map", "akt signaling and raf/map kinase", "signaling and raf/map kinase cascade.", "and raf/map kinase cascade. signaling", "raf/map kinase cascade. signaling by", "kinase cascade. signaling by erbb3", "cascade. signaling by erbb3 is", "signaling by erbb3 is downregulated", "by erbb3 is downregulated by", "erbb3 is downregulated by the", "is downregulated by the action", "downregulated by the action of", "by the action of rnf41", "the action of rnf41 ubiquitin", "action of rnf41 ubiquitin ligase", "rnf41 ubiquitin ligase also", "ubiquitin ligase also known", "ligase also known as", "also known as nrdp1.

", "known as nrdp1.

in", "as nrdp1.

in cells", "nrdp1.

in cells expressing", "

in cells expressing erbb2", "cells expressing erbb2 and erbb4", "erbb2 and erbb4 ligand", "and erbb4 ligand stimulated", "erbb4 ligand stimulated erbb4", "ligand stimulated erbb4 can either", "stimulated erbb4 can either homodimerize", "erbb4 can either homodimerize or", "can either homodimerize or form", "either homodimerize or form heterodimers", "homodimerize or form heterodimers with", "or form heterodimers with erbb2", "heterodimers with erbb2 li", "with erbb2 li et", "erbb2 li et al.", "al. 2007 resulting", "2007 resulting in", "resulting in trans autophosphorylation of", "in trans autophosphorylation of erbb2", "trans autophosphorylation of erbb2 and", "autophosphorylation of erbb2 and erbb4", "of erbb2 and erbb4 on", "erbb2 and erbb4 on c", "and erbb4 on c tail", "erbb4 on c tail tyrosine", "on c tail tyrosine residues", "c tail tyrosine residues that", "tail tyrosine residues that will", "tyrosine residues that will subsequently", "residues that will subsequently serve", "that will subsequently serve as", "will subsequently serve as docking", "downstream signaling molecules leading", "signaling molecules leading to", "molecules leading to activation", "leading to activation of raf/map", "to activation of raf/map kinase", "activation of raf/map kinase cascade", "of raf/map kinase cascade and", "kinase cascade and in", "cascade and in the", "and in the case", "in the case of erbb4", "the case of erbb4 cyt1", "case of erbb4 cyt1 isoforms", "erbb4 cyt1 isoforms pi3k", "cyt1 isoforms pi3k induced", "isoforms pi3k induced akt", "induced akt signaling hazan", "akt signaling hazan et", "signaling hazan et al.", "et al. 1990 cohen", "al. 1990 cohen et", "1990 cohen et al.", "et al. 1996 li", "al. 1996 li et", "1996 li et al.", "et al. 2007 kaushansky", "al. 2007 kaushansky et", "2007 kaushansky et al.", "kaushansky et al. 2008 .", "et al. 2008 . signaling", "al. 2008 . signaling by", "2008 . signaling by erbb4", ". signaling by erbb4 is", "signaling by erbb4 is downregulated", "by erbb4 is downregulated by", "erbb4 is downregulated by the", "by the action of wwp1", "the action of wwp1 and", "action of wwp1 and itch", "of wwp1 and itch ubiquitin", "wwp1 and itch ubiquitin ligases", "itch ubiquitin ligases and", "ubiquitin ligases and is", "ligases and is shown", "shown under signaling by erbb4." ] }, { "record_id": "GLY_000594_1_29", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1234176", "r hsa", "hsa 1234176", "r hsa 1234176" ] }, { "record_id": "GLY_000594_1_29", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "oxygen dependent", "dependent proline", "proline hydroxylation", "hydroxylation of", "of hypoxia", "hypoxia inducible", "inducible factor", "factor alpha", "oxygen dependent proline", "dependent proline hydroxylation", "proline hydroxylation of", "hydroxylation of hypoxia", "of hypoxia inducible", "hypoxia inducible factor", "inducible factor alpha", "oxygen dependent proline hydroxylation", "dependent proline hydroxylation of", "proline hydroxylation of hypoxia", "hydroxylation of hypoxia inducible", "of hypoxia inducible factor", "hypoxia inducible factor alpha", "oxygen dependent proline hydroxylation of", "dependent proline hydroxylation of hypoxia", "proline hydroxylation of hypoxia inducible", "hydroxylation of hypoxia inducible factor", "of hypoxia inducible factor alpha", "hif alpha", "alpha subunits", "comprising hif1a", "bruick and", "and mcknight", "mcknight 2001", "ivan et", "et al.", "al. 2001", "jaakkola et", "percy et", "al. 2008", "furlow et", "al. 2009", "and hif3a", "maynard et", "al. 2003", "are hydroxylated", "hydroxylated at", "at proline", "proline residues", "residues by", "by the", "the prolyl", "prolyl hydroxylases", "hydroxylases phd1", "and phd3", "berra et", "hirsila et", "metzen et", "tuckerman et", "al. 2004", "appelhoff et", "fedulova et", "al. 2007", "tian et", "al. 2011", "2011 .", ". the", "the reaction", "reaction requires", "requires molecular", "molecular oxygen", "oxygen as", "as a", "a substrate", "substrate and", "and so", "so it", "it is", "is inhibited", "inhibited by", "by hypoxia.", "hypoxia. phd2", "is predominantly", "predominantly cytosolic", "and is", "is the", "the key", "key determinant", "determinant in", "in the", "the regulation", "regulation of", "of hif", "subunits by", "by oxygen", "2003 .
hif", ".
hif alpha", "subunits hydroxylated", "residues are", "are bound", "bound by", "by vhl", "an e3", "e3 ubiquitin", "ubiquitin ligase", "ligase in", "in a", "a complex", "complex containing", "containing elonginb", "elongin c", "and rbx1.", "rbx1. vhl", "vhl ubiquitinates", "ubiquitinates hif", "resulting in", "in destruction", "destruction of", "alpha by", "by proteolysis.", "proteolysis. hypoxia", "hypoxia inhibits", "inhibits proline", "hydroxylation and", "and interaction", "interaction with", "with vhl", "stabilizing hif", "which transits", "transits to", "to the", "the nucleus", "nucleus and", "and activates", "activates gene", "gene expression.", "hif alpha subunits", "subunits comprising", "hif1a bruick", "bruick and mcknight", "and mcknight 2001", "2001 ivan", "ivan et al.", "et al. 2001", "2001 jaakkola", "jaakkola et al.", "hif2a percy", "percy et al.", "et al. 2008", "2008 furlow", "furlow et al.", "et al. 2009", "hif3a maynard", "maynard et al.", "et al. 2003", "are hydroxylated at", "hydroxylated at proline", "at proline residues", "proline residues by", "residues by the", "by the prolyl", "the prolyl hydroxylases", "prolyl hydroxylases phd1", "phd1 egln2", "phd2 egln1", "phd3 egln3", "2001 berra", "berra et al.", "2003 hirsila", "hirsila et al.", "2003 metzen", "metzen et al.", "2003 tuckerman", "tuckerman et al.", "et al. 2004", "2004 appelhoff", "appelhoff et al.", "2004 fedulova", "fedulova et al.", "et al. 2007", "2007 tian", "tian et al.", "et al. 2011", "al. 2011 .", "2011 . the", ". the reaction", "the reaction requires", "reaction requires molecular", "requires molecular oxygen", "molecular oxygen as", "oxygen as a", "as a substrate", "a substrate and", "substrate and so", "and so it", "so it is", "it is inhibited", "is inhibited by", "inhibited by hypoxia.", "by hypoxia. phd2", "egln1 is", "is predominantly cytosolic", "cytosolic metzen", "2003 and", "and is the", "is the key", "the key determinant", "key determinant in", "determinant in the", "in the regulation", "the regulation of", "regulation of hif", "of hif alpha", "alpha subunits by", "subunits by oxygen", "oxygen berra", "al. 2003 .
hif", "2003 .
hif alpha", ".
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hif", "al. 2003 .
hif alpha", "2003 .
hif alpha subunits", ".
hif alpha subunits hydroxylated", "alpha subunits hydroxylated at", "subunits hydroxylated at proline", "at proline residues are", "proline residues are bound", "residues are bound by", "are bound by vhl", "by vhl an", "vhl an e3", "an e3 ubiquitin ligase", "e3 ubiquitin ligase in", "ubiquitin ligase in a", "ligase in a complex", "in a complex containing", "a complex containing elonginb", "containing elonginb elongin", "elonginb elongin c", "elongin c cul2", "cul2 and rbx1.", "and rbx1. vhl ubiquitinates", "rbx1. vhl ubiquitinates hif", "vhl ubiquitinates hif alpha", "hif alpha resulting", "alpha resulting in", "resulting in destruction of", "in destruction of hif", "destruction of hif alpha", "of hif alpha by", "hif alpha by proteolysis.", "alpha by proteolysis. hypoxia", "by proteolysis. hypoxia inhibits", "proteolysis. hypoxia inhibits proline", "hypoxia inhibits proline hydroxylation", "inhibits proline hydroxylation and", "proline hydroxylation and interaction", "hydroxylation and interaction with", "and interaction with vhl", "with vhl stabilizing", "vhl stabilizing hif", "hif alpha which", "alpha which transits", "which transits to the", "transits to the nucleus", "to the nucleus and", "the nucleus and activates", "nucleus and activates gene", "and activates gene expression.", "hif alpha subunits comprising", "alpha subunits comprising hif1a", "comprising hif1a bruick and", "hif1a bruick and mcknight", "and mcknight 2001 ivan", "mcknight 2001 ivan et", "2001 ivan et al.", "et al. 2001 jaakkola", "al. 2001 jaakkola et", "2001 jaakkola et al.", "al. 2001 hif2a", "hif2a percy et al.", "et al. 2008 furlow", "al. 2008 furlow et", "2008 furlow et al.", "al. 2009 and", "2009 and hif3a", "and hif3a maynard et", "hif3a maynard et al.", "al. 2003 are", "2003 are hydroxylated", "are hydroxylated at proline residues", "hydroxylated at proline residues by", "at proline residues by the", "proline residues by the prolyl", "residues by the prolyl hydroxylases", "by the prolyl hydroxylases phd1", "prolyl hydroxylases phd1 egln2", "egln1 and phd3", "egln3 bruick and", "and mcknight 2001 berra", "mcknight 2001 berra et", "2001 berra et al.", "et al. 2003 hirsila", "al. 2003 hirsila et", "2003 hirsila et al.", "et al. 2003 metzen", "al. 2003 metzen et", "2003 metzen et al.", "et al. 2003 tuckerman", "al. 2003 tuckerman et", "2003 tuckerman et al.", "et al. 2004 appelhoff", "al. 2004 appelhoff et", "2004 appelhoff et al.", "et al. 2004 fedulova", "al. 2004 fedulova et", "2004 fedulova et al.", "et al. 2007 tian", "al. 2007 tian et", "2007 tian et al.", "tian et al. 2011 .", "et al. 2011 . the", "al. 2011 . the reaction", "2011 . the reaction requires", ". the reaction requires molecular", "the reaction requires molecular oxygen", "reaction requires molecular oxygen as", "requires molecular oxygen as a", "molecular oxygen as a substrate", "oxygen as a substrate and", "as a substrate and so", "a substrate and so it", "substrate and so it is", "and so it is inhibited", "so it is inhibited by", "it is inhibited by hypoxia.", "is inhibited by hypoxia. phd2", "by hypoxia. phd2 egln1", "phd2 egln1 is", "egln1 is predominantly cytosolic", "is predominantly cytosolic metzen", "predominantly cytosolic metzen et", "cytosolic metzen et al.", "et al. 2003 and", "al. 2003 and is", "2003 and is the", "and is the key determinant", "is the key determinant in", "the key determinant in the", "key determinant in the regulation", "determinant in the regulation of", "in the regulation of hif", "the regulation of hif alpha", "regulation of hif alpha subunits", "of hif alpha subunits by", "hif alpha subunits by oxygen", "subunits by oxygen berra", "by oxygen berra et", "oxygen berra et al.", "berra et al. 2003 .
hif", "et al. 2003 .
hif alpha", "al. 2003 .
hif alpha subunits", "2003 .
hif alpha subunits hydroxylated", ".
hif alpha subunits hydroxylated at", "alpha subunits hydroxylated at proline", "subunits hydroxylated at proline residues", "hydroxylated at proline residues are", "at proline residues are bound", "proline residues are bound by", "residues are bound by vhl", "bound by vhl an", "by vhl an e3", "vhl an e3 ubiquitin", "an e3 ubiquitin ligase in", "e3 ubiquitin ligase in a", "ubiquitin ligase in a complex", "ligase in a complex containing", "in a complex containing elonginb", "complex containing elonginb elongin", "containing elonginb elongin c", "c cul2 and", "cul2 and rbx1. vhl", "and rbx1. vhl ubiquitinates hif", "rbx1. vhl ubiquitinates hif alpha", "ubiquitinates hif alpha resulting", "hif alpha resulting in", "alpha resulting in destruction", "resulting in destruction of hif", "in destruction of hif alpha", "destruction of hif alpha by", "of hif alpha by proteolysis.", "hif alpha by proteolysis. hypoxia", "alpha by proteolysis. hypoxia inhibits", "by proteolysis. hypoxia inhibits proline", "proteolysis. hypoxia inhibits proline hydroxylation", "hypoxia inhibits proline hydroxylation and", "inhibits proline hydroxylation and interaction", "proline hydroxylation and interaction with", "hydroxylation and interaction with vhl", "interaction with vhl stabilizing", "with vhl stabilizing hif", "vhl stabilizing hif alpha", "stabilizing hif alpha which", "hif alpha which transits", "alpha which transits to", "which transits to the nucleus", "transits to the nucleus and", "to the nucleus and activates", "the nucleus and activates gene", "nucleus and activates gene expression." ] }, { "record_id": "GLY_000594_1_30", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1236394", "r hsa", "hsa 1236394", "r hsa 1236394" ] }, { "record_id": "GLY_000594_1_30", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by erbb4", "signaling by erbb4", "also known", "known as", "as her4", "belongs to", "to the", "the erbb", "erbb family", "family of", "of receptors", "which also", "also includes", "includes erbb1", "and erbb3", "her3 .", ". similar", "similar to", "to egfr", "erbb4 has", "has an", "an extracellular", "extracellular ligand", "ligand binding", "binding domain", "a single", "single transmembrane", "transmembrane domain", "domain and", "and a", "a cytoplasmic", "cytoplasmic domain", "domain which", "which contains", "contains an", "an active", "active tyrosine", "tyrosine kinase", "kinase and", "a c", "c tail", "tail with", "with multiple", "multiple phosphorylation", "phosphorylation sites.", "sites. at", "at least", "least three", "three and", "and possibly", "possibly four", "four splicing", "splicing isoforms", "isoforms of", "of erbb4", "erbb4 exist", "exist that", "that differ", "differ in", "in their", "their c", "tail and/or", "and/or the", "the extracellular", "extracellular juxtamembrane", "juxtamembrane regions:", "regions: erbb4", "erbb4 jm", "jm a", "a cyt1", "a cyt2", "cyt2 and", "and erbb4", "jm b", "b cyt1", "the existence", "existence of", "b cyt2", "cyt2 has", "has not", "not been", "been confirmed", "confirmed .", ".

erbb4", "

erbb4 becomes", "becomes activated", "activated by", "by binding", "binding one", "one of", "of its", "its seven", "seven ligands", "three of", "of which", "hb egf", "epiregulin epr", "epr and", "and betacellulin", "betacellulin btc", "are egf", "egf like", "elenius et", "et al.", "al. 1997", "riese et", "al. 1998", "while four", "nrg3 and", "and nrg4", "belong to", "the related", "related neuregulin", "neuregulin family", "tzahar et", "al. 1994", "carraway et", "zhang et", "hayes et", "al. 2007", "2007 .", ". upon", "upon ligand", "erbb4 forms", "forms homodimers", "sweeney et", "al. 2000", "or it", "it heterodimerizes", "heterodimerizes with", "with erbb2", "li et", ". dimers", "dimers of", "erbb4 undergo", "undergo trans", "trans autophosphorylation", "autophosphorylation on", "on tyrosine", "tyrosine residues", "residues in", "in the", "the c", "cohen et", "al. 1996", "kaushansky et", "al. 2008", "hazan et", "al. 1990", "triggering downstream", "downstream signaling", "signaling cascades.", "cascades. the", "the pathway", "pathway signaling", "erbb4 only", "only shows", "shows signaling", "erbb4 homodimers.", "homodimers. signaling", "by heterodimers", "heterodimers of", "erbb4 and", "and erbb2", "erbb2 is", "is shown", "shown in", "by erbb2.", "erbb2. ligand", "ligand stimulated", "stimulated erbb4", "erbb4 is", "is also", "also able", "able to", "to form", "form heterodimers", "heterodimers with", "with ligand", "stimulated egfr", "and ligand", "stimulated erbb3", "al. 1995", "1995 .", "erbb4 with", "with egfr", "egfr and", "and dimers", "with erbb3", "erbb3 were", "were demonstrated", "demonstrated in", "in mouse", "mouse cell", "cell lines", "lines in", "in which", "which human", "human erbb4", "and egfr", "egfr or", "or erbb3", "were exogenously", "exogenously expressed.", "expressed. these", "these heterodimers", "heterodimers undergo", "trans autophosphorylation.", "autophosphorylation. the", "the promiscuous", "promiscuous heteromerization", "heteromerization of", "of erbbs", "erbbs adds", "adds combinatorial", "combinatorial diversity", "diversity to", "to erbb", "erbb signaling", "signaling processes.", "processes. as", "as erbb4", "erbb4 binds", "binds more", "more ligands", "ligands than", "than other", "other erbbs", "but has", "has restricted", "restricted expression", "erbb4 expression", "expression channels", "channels responses", "responses to", "erbb ligands.", "ligands. the", "the signaling", "signaling capabilities", "capabilities of", "of the", "the four", "four receptors", "receptors have", "have been", "been compared", "schulze et", "al. 2005", "2005 .

as", ".

as for", "for other", "other receptor", "receptor tyrosine", "tyrosine kinases", "erbb4 signaling", "signaling effectors", "effectors are", "are largely", "largely dictated", "dictated through", "through binding", "binding of", "of effector", "effector proteins", "proteins to", "to erbb4", "erbb4 peptides", "peptides that", "that are", "are phosphorylated", "phosphorylated upon", "ligand binding.", "binding. all", "all splicing", "erbb4 possess", "possess two", "two tyrosine", "tail that", "that serve", "serve as", "as docking", "docking sites", "sites for", "for shc1", "pinkas kramarski", "kramarski et", "1996 .", ". once", "once bound", "bound to", "shc1 becomes", "becomes phosphorylated", "phosphorylated on", "residues by", "by the", "the tyrosine", "kinase activity", "activity of", "which enables", "enables it", "it to", "to recruit", "recruit the", "the complex", "complex of", "of grb2", "grb2 and", "and sos1", "resulting in", "the guanyl", "guanyl nucleotide", "nucleotide exchange", "exchange on", "on ras", "ras and", "and activation", "activation of", "of raf", "raf and", "and map", "map kinase", "kinase cascade", "kainulainen et", "2000 .", ".

the", "

the cyt1", "cyt1 isoforms", "erbb4 also", "also possess", "possess a", "tail tyrosine", "tyrosine residue", "residue that", "upon trans", "serves as", "as a", "a docking", "docking site", "site for", "for the", "the p85", "p85 alpha", "alpha subunit", "subunit of", "of pi3k", "leading to", "to assembly", "assembly of", "of an", "active pi3k", "pi3k complex", "complex that", "that converts", "converts pip2", "pip2 to", "to pip3", "pip3 and", "and activates", "activates akt", "akt signaling", ".

besides", "

besides signaling", "signaling as", "a conventional", "conventional transmembrane", "transmembrane receptor", "receptor kinase", "erbb4 differs", "differs from", "from other", "erbbs in", "in that", "that jm", "a isoforms", "isoforms signal", "signal through", "through efficient", "efficient release", "release of", "of a", "a soluble", "soluble intracellular", "intracellular domain.", "domain. ligand", "ligand activated", "activated homodimers", "homodimers of", "cyt1 and", "undergo proteolytic", "proteolytic cleavage", "cleavage by", "by adam17", "the juxtamembrane", "juxtamembrane region", "in shedding", "shedding of", "extracellular domain", "and formation", "formation of", "an 80", "80 kda", "kda membrane", "membrane bound", "bound erbb4", "erbb4 fragment", "fragment known", "erbb4 m80", "rio et", "cheng et", "al. 2003", "2003 .", ". erbb4", "m80 undergoes", "undergoes further", "further proteolytic", "mediated by", "the gamma", "gamma secretase", "secretase complex", "which releases", "releases the", "the soluble", "soluble 80", "kda erbb4", "erbb4 intracellular", "intracellular domain", "erbb4 s80", "s80 or", "or e4icd", "into the", "the cytosol", "ni et", "al. 2001", "2001 .", "s80 is", "is able", "to translocate", "translocate to", "the nucleus", "promote nuclear", "nuclear translocation", "translocation of", "of various", "various transcription", "transcription factors", "and act", "act as", "a transcription", "transcription co", "co factor.", "factor. for", "for example", "in mammary", "mammary cells", "binds sh2", "sh2 transcription", "transcription factor", "factor stat5a.", "stat5a. erbb4", "s80 shuttles", "shuttles stat5a", "stat5a to", "and actsa", "actsa as", "a stat5a", "stat5a co", "co factor", "factor in", "in binding", "binding to", "to and", "and promoting", "promoting transcription", "transcription from", "from the", "the beta", "beta casein", "and may", "may be", "be involved", "involved in", "the regulation", "regulation of", "of other", "other lactation", "lactation related", "related genes", "jones et", "al. 1999", "williams et", "al. 2004", "muraoka cook", "cook et", "2008 .", "s80 binds", "binds activated", "activated estrogen", "estrogen receptor", "receptor in", "nucleus and", "and acts", "acts as", "a transcriptional", "transcriptional co", "in promoting", "transcription of", "of some", "some estrogen", "estrogen regulated", "regulated genes", "including progesterone", "progesterone receptor", "receptor gene", "gene nr3c3", "nr3c3 and", "and cxcl12", "zhu et", "al. 2006", "2006 .", ". in", "in neuronal", "neuronal precursors", "binds the", "of tab", "tab and", "and ncor1", "helps to", "to move", "move the", "complex into", "and is", "is a", "a co", "factor of", "of tab:ncor1", "tab:ncor1 mediated", "mediated inhibition", "inhibition of", "of expression", "expression of", "of astrocyte", "astrocyte differentiation", "differentiation genes", "genes gfap", "gfap and", "and s100b", "sardi et", "2006 .

the", ".

the c", "tail of", "erbb4 possesses", "possesses several", "several ww", "ww domain", "domain binding", "binding motifs", "three in", "in cyt1", "cyt1 isoform", "isoform and", "and two", "two in", "in cyt2", "cyt2 isoform", "which enable", "enable interaction", "interaction of", "with ww", "domain containing", "containing proteins.", "proteins. erbb4", "through ww", "interacts with", "with yap1", "yap1 transcription", "a known", "known proto", "proto oncogene", "co regulator", "regulator of", "of yap1", "yap1 mediated", "mediated transcription", "transcription in", "in association", "association with", "with tead", "tead transcription", "komuro et", "omerovic et", "2004 .", ". hence", "the ww", "ww binding", "binding motif", "motif couples", "couples erbb4", "erbb4 to", "the major", "major effector", "effector arm", "arm of", "the hippo", "hippo signaling", "signaling pathway.", "pathway. the", "the tumor", "tumor suppressor", "suppressor wwox", "another ww", "containing protein", "competes with", "yap1 in", "s80 and", "and prevents", "prevents translocation", "s80 to", "aqeilan et", "2005 .

ww", ".

ww domain", "motifs in", "erbb4 play", "play an", "an important", "important role", "role in", "the downregulation", "downregulation of", "erbb4 receptor", "receptor signaling", "enabling the", "the interaction", "of intact", "intact erbb4", "m80 and", "s80 with", "with nedd4", "nedd4 family", "of e3", "e3 ubiquitin", "ubiquitin ligases", "ligases wwp1", "wwp1 and", "and itch.", "itch. the", "of wwp1", "and itch", "itch with", "with intact", "is independent", "independent of", "of receptor", "receptor activation", "activation and", "and autophosphorylation.", "autophosphorylation. binding", "itch ubiquitin", "ligases leads", "leads to", "to ubiquitination", "ubiquitination of", "and its", "its cleavage", "cleavage products", "and subsequent", "subsequent degradation", "degradation through", "through both", "both proteasomal", "proteasomal and", "and lysosomal", "lysosomal routes", "feng et", "al. 2009", "2009 .", "in addition", "the s80", "s80 cleavage", "cleavage product", "product of", "a cyt", "cyt 1", "1 isoform", "isoform is", "is the", "the target", "target of", "of nedd4", "nedd4 ubiquitin", "ubiquitin ligase.", "ligase. nedd4", "nedd4 binds", "binds erbb4", "1 s80", "through its", "its pik3r1", "pik3r1 interaction", "interaction site", "site and", "and mediates", "mediates erbb4jmacyt1s80", "erbb4jmacyt1s80 ubiquitination", "thereby decreasing", "decreasing the", "the amount", "amount of", "of erbb4jmacyt1s80", "erbb4jmacyt1s80 that", "that reaches", "reaches the", "zeng et", "2009 .

erbb4", ".

erbb4 also", "also binds", "the e3", "ubiquitin ligase", "ligase mdm2", "and inhibitor", "inhibitor of", "of p53", "arasada et", "2005 .", ". other", "other proteins", "proteins that", "that bind", "bind to", "domain have", "been identified", "identified by", "by co", "co immunoprecipitation", "immunoprecipitation and", "and mass", "mass spectrometry", "gilmore hebert", "hebert et", "and include", "include transcriptional", "co repressor", "repressor trim28/kap1", "which promotes", "promotes chromatin", "chromatin compaction.", "compaction. dna", "dna damage", "damage signaling", "signaling through", "through atm", "atm releases", "releases trim28", "trim28 associated", "associated heterochromatinization.", "heterochromatinization. interactions", "interactions of", "with trim28", "trim28 and", "and mdm2", "mdm2 may", "be important", "important for", "for integration", "integration of", "of growth", "growth factor", "factor responses", "responses and", "and dna", "damage responses.

in", "responses.

in human", "human breast", "breast cancer", "cancer cell", "erbb4 activation", "activation enhances", "enhances anchorage", "anchorage independent", "independent colony", "colony formation", "formation in", "in soft", "soft agar", "agar but", "but inhibits", "inhibits cell", "cell growth", "growth in", "in a", "a monolayer", "monolayer culture.", "culture. different", "different erbb4", "erbb4 ligands", "ligands induce", "induce different", "different gene", "gene expression", "expression changes", "changes in", "in breast", "cell lines.", "lines. some", "some of", "the genes", "genes induced", "induced in", "in response", "response to", "signaling in", "lines are", "are rab2", "eps15r and", "and gata4.", "gata4. it", "it is", "is not", "not known", "known if", "if these", "these gene", "gene are", "are direct", "direct transcriptional", "transcriptional targets", "targets of", "amin et", "2004 .

transcriptome", ".

transcriptome and", "and chip", "chip seq", "seq comparisons", "comparisons of", "of full", "full length", "length and", "and intracellular", "domain isoforms", "isoforms in", "in isogenic", "isogenic mcf10a", "mcf10a mammary", "mammary cell", "cell background", "background have", "have revealed", "revealed the", "the diversification", "diversification of", "signaling engendered", "engendered by", "by alternative", "alternative splicing", "splicing and", "and cleavage", "wali et", "2014 .", "erbb4 broadly", "broadly affected", "affected protease", "protease expression", "cholesterol biosynthesis", "hif1 alpha", "alpha signaling", "and hippo", "signaling pathways", "and other", "other pathways", "pathways were", "were differentially", "differentially activated", "by cyt1", "and cyt2", "cyt2 isoforms.", "isoforms. for", "cyt1 promoted", "promoted expression", "of transcription", "factors twist1", "twist1 and", "and snail1", "snail1 that", "that promote", "promote epithelial", "epithelial mesenchymal", "mesenchymal transition.", "transition. hif1", "alpha and", "signaling are", "are mediated", "to hif1", "and to", "to yap", "paatero et", "erbb4 increases", "increases activity", "the transcription", "factor srebf2", "in increased", "increased expression", "of srebf2", "srebf2 target", "target genes", "genes involved", "in cholesterol", "cholesterol biosynthesis.", "biosynthesis. the", "the mechanism", "mechanism is", "known and", "may involve", "involve facilitation", "facilitation of", "srebf2 cleavage", "cleavage through", "through erbb4", "erbb4 mediated", "mediated pi3k", "pi3k signaling", "haskins et", "al. 2016", "2016 .

in", ".

in some", "some contexts", "erbb4 promotes", "promotes growth", "growth suppression", "suppression or", "or apoptosis", "penington et", "2002 .", ". activation", "erbb4 in", "lines leads", "to jnk", "jnk dependent", "dependent increase", "increase in", "in brca1", "brca1 mrna", "mrna level", "level and", "and mitotic", "mitotic cell", "cell cycle", "cycle delay", "but the", "the exact", "exact mechanism", "mechanism has", "been elucidated", ". the", "the nature", "nature of", "growth responses", "responses may", "be connected", "connected with", "with the", "the spliced", "spliced isoforms", "isoforms expressed.", "expressed. in", "in comparisons", "of cyt1", "cyt1 vs", "vs cyt2", "and icd", "expression in", "cyt1 was", "was a", "a weaker", "weaker growth", "growth inducer", "associated with", "with attenuated", "attenuated mapk", "mapk signaling", "signaling relative", "relative to", "to cyt2", "the mitochondrial", "mitochondrial matrix", "presumably when", "when its", "its nuclear", "translocation is", "is inhibited.", "inhibited. once", "once in", "the mitochondrion", "the bh3", "bh3 domain", "domain of", "characteristic of", "of bcl2", "bcl2 family", "family members", "may enable", "enable it", "to act", "a pro", "pro apoptotic", "apoptotic factor", "naresh et", "2006 .

erbb4", ".

erbb4 plays", "plays important", "important roles", "roles in", "the developing", "developing and", "and adult", "adult nervous", "nervous system.", "system. erbb4", "erbb4 deficiency", "deficiency in", "in somatostatin", "somatostatin expressing", "expressing neurons", "neurons of", "the thalamic", "thalamic reticular", "reticular nucleus", "nucleus alters", "alters behaviors", "behaviors dependent", "dependent on", "on sensory", "sensory selection", "ahrens et", "al. 2015", "2015 .", ". nrg1", "nrg1 activated", "activated erbb4", "signaling enhances", "enhances ampa", "ampa receptor", "receptor responses", "responses through", "through pkc", "pkc dependent", "dependent ampa", "receptor exocytosis.", "exocytosis. this", "this results", "results in", "in an", "an increased", "increased excitatory", "excitatory input", "input to", "to parvalbumin", "parvalbumin expressing", "expressing inhibitory", "inhibitory neurons", "neurons in", "the visual", "visual cortex", "cortex and", "and regulates", "regulates visual", "visual cortical", "cortical plasticity", "sun et", "2016 .", "signaling is", "is involved", "in gabaergic", "gabaergic activity", "activity in", "in amygdala", "amygdala which", "which mediates", "mediates fear", "fear conditioning", "fear memory", "lu et", "al. 2014", ". conditional", "conditional erbb4", "erbb4 deletion", "deletion from", "from fast", "fast spiking", "spiking interneurons", "chandelier and", "and basket", "basket cells", "cells of", "the cerebral", "cerebral cortex", "cortex leads", "to synaptic", "synaptic defects", "defects associated", "with increased", "increased locomotor", "locomotor activity", "activity and", "and abnormal", "abnormal emotional", "social and", "and cognitive", "cognitive function", "function that", "that can", "can be", "be linked", "linked to", "to some", "the schizophrenia", "schizophrenia features.", "features. the", "the level", "level of", "of gad1", "protein is", "is reduced", "reduced in", "the cortex", "cortex of", "of conditional", "erbb4 mutants.", "mutants. gad1", "gad1 is", "a gaba", "gaba synthesizing", "synthesizing enzyme.", "enzyme. cortical", "cortical mrna", "mrna levels", "levels of", "of gad67", "gad67 are", "are consistently", "consistently decreased", "decreased in", "in schizophrenia", "del pino", "pino et", "is expressed", "expressed in", "the gabaergic", "gabaergic neurons", "the bed", "bed nucleus", "nucleus stria", "stria terminalis", "a part", "part of", "the extended", "extended amygdala.", "amygdala. inhibition", "of nrg1", "nrg1 triggered", "triggered erbb4", "signaling induces", "induces anxiety", "anxiety like", "like behavior", "which depends", "depends on", "on gabaergic", "gabaergic neurotransmission.", "neurotransmission. nrg1", "nrg1 erbb4", "signaling stimulates", "stimulates presynaptic", "presynaptic gaba", "gaba release", "geng et", "nrg1 protects", "protects cortical", "cortical interneurons", "interneurons against", "against ischemic", "ischemic brain", "brain injury", "injury through", "mediated increase", "gabaergic transmission", "guan et", ". nrg2", "nrg2 activated", "erbb4 can", "can reduce", "reduce the", "the duration", "duration of", "of gabaergic", "transmission by", "to gaba", "gaba receptors", "receptors at", "at the", "the postsynaptic", "postsynaptic membrane", "membrane via", "via their", "their gabra1", "gabra1 subunit", "subunit and", "promoting endocytosis", "endocytosis of", "of gaba", "mitchell et", "al. 2013", "2013 .", "nrg1 promotes", "promotes synchronization", "synchronization of", "of prefrontal", "prefrontal cortex", "cortex interneurons", "interneurons in", "an erbb4", "erbb4 dependent", "dependent manner", "hou et", "signaling protects", "protects neurons", "neurons from", "the cell", "cell death", "death induced", "induced by", "by a", "a mutant", "mutant form", "form of", "the amyloid", "amyloid precursor", "precursor protein", "woo et", "al. 2012", "2012 .

clinical", ".

clinical relevance", "relevance of", "has been", "identified in", "in several", "several contexts.", "contexts. in", "in cancer", "putative and", "and validated", "validated gain", "gain of", "of function", "function mutations", "mutations or", "or gene", "gene amplification", "amplification that", "that may", "be drivers", "drivers have", "identified at", "at modest", "modest frequencies", "may also", "also contribute", "contribute to", "to resistance", "resistance to", "erbb2 targeted", "targeted therapies.", "therapies. this", "this is", "is noteworthy", "noteworthy as", "erbb4 kinase", "activity is", "is inhibited", "inhibited by", "by pan", "pan erbb", "erbb tyrosine", "kinase inhibitors", "including lapatinib", "which is", "is approved", "approved by", "the us", "us fda.", "fda. the", "the reduced", "reduced prevalence", "prevalence relative", "erbb2 in", "cancer may", "may reflect", "reflect more", "more restricted", "or differential", "differential signaling", "as specific", "specific erbb4", "erbb4 isoforms", "isoforms have", "been linked", "to growth", "growth inhibition", "inhibition or", "apoptosis in", "in experimental", "experimental systems.", "systems. erbb2/erbb4", "erbb2/erbb4 heterodimers", "heterodimers protect", "protect cardiomyocytes", "so reduced", "reduced activity", "in patients", "patients treated", "treated with", "the erbb2", "targeted therapeutic", "therapeutic antibody", "antibody trastuzumab", "trastuzumab may", "may contribute", "the cardiotoxicity", "cardiotoxicity of", "of this", "this agent", "agent when", "when used", "used in", "in combination", "combination with", "anthracyclines.

with the", "the importance", "importance of", "in developing", "nervous system", "nrg1 and/or", "and/or erbb4", "erbb4 polymorphisms", "splicing aberrations", "aberrations and", "and mutations", "mutations have", "to nervous", "system disorders", "disorders including", "including schizophrenia", "schizophrenia and", "and amyotrophic", "amyotrophic lateral", "lateral sclerosis", "although these", "these findings", "findings are", "are not", "not yet", "yet definitive.", "also known as", "known as her4", "her4 belongs", "belongs to the", "to the erbb", "the erbb family", "erbb family of", "family of receptors", "receptors which", "which also includes", "also includes erbb1", "erbb1 egfr/her1", "erbb2 her2/neu", "her2/neu and", "erbb3 her3", "her3 . similar", ". similar to", "similar to egfr", "egfr erbb4", "erbb4 has an", "has an extracellular", "an extracellular ligand", "extracellular ligand binding", "ligand binding domain", "domain a", "a single transmembrane", "single transmembrane domain", "transmembrane domain and", "domain and a", "and a cytoplasmic", "a cytoplasmic domain", "cytoplasmic domain which", "domain which contains", "which contains an", "contains an active", "an active tyrosine", "active tyrosine kinase", "tyrosine kinase and", "kinase and a", "and a c", "a c tail", "c tail with", "tail with multiple", "with multiple phosphorylation", "multiple phosphorylation sites.", "phosphorylation sites. at", "sites. at least", "at least three", "least three and", "three and possibly", "and possibly four", "possibly four splicing", "four splicing isoforms", "splicing isoforms of", "isoforms of erbb4", "of erbb4 exist", "erbb4 exist that", "exist that differ", "that differ in", "differ in their", "in their c", "their c tail", "c tail and/or", "tail and/or the", "and/or the extracellular", "the extracellular juxtamembrane", "extracellular juxtamembrane regions:", "juxtamembrane regions: erbb4", "regions: erbb4 jm", "erbb4 jm a", "jm a cyt1", "cyt1 erbb4", "jm a cyt2", "a cyt2 and", "cyt2 and erbb4", "and erbb4 jm", "erbb4 jm b", "jm b cyt1", "cyt1 the", "the existence of", "existence of erbb4", "of erbb4 jm", "jm b cyt2", "b cyt2 has", "cyt2 has not", "has not been", "not been confirmed", "been confirmed .", "confirmed .

erbb4", ".

erbb4 becomes", "

erbb4 becomes activated", "becomes activated by", "activated by binding", "by binding one", "binding one of", "one of its", "of its seven", "its seven ligands", "ligands three", "three of which", "which hb", "egf epiregulin", "epiregulin epr and", "epr and betacellulin", "and betacellulin btc", "btc are", "are egf like", "like elenius", "elenius et al.", "et al. 1997", "1997 riese", "riese et al.", "et al. 1998", "four nrg1", "nrg1 nrg2", "nrg2 nrg3", "nrg3 and nrg4", "nrg4 belong", "belong to the", "to the related", "the related neuregulin", "related neuregulin family", "family tzahar", "tzahar et al.", "et al. 1994", "1994 carraway", "carraway et al.", "1997 zhang", "zhang et al.", "1997 hayes", "hayes et al.", "et al. 2007", "al. 2007 .", "2007 . upon", ". upon ligand", "upon ligand binding", "binding erbb4", "erbb4 forms homodimers", "homodimers sweeney", "sweeney et al.", "et al. 2000", "2000 or", "or it heterodimerizes", "it heterodimerizes with", "heterodimerizes with erbb2", "erbb2 li", "li et al.", "2007 . dimers", ". dimers of", "dimers of erbb4", "of erbb4 undergo", "erbb4 undergo trans", "undergo trans autophosphorylation", "trans autophosphorylation on", "autophosphorylation on tyrosine", "on tyrosine residues", "tyrosine residues in", "residues in the", "in the c", "the c tail", "tail cohen", "cohen et al.", "et al. 1996", "1996 kaushansky", "kaushansky et al.", "et al. 2008", "2008 hazan", "hazan et al.", "et al. 1990", "1990 li", "triggering downstream signaling", "downstream signaling cascades.", "signaling cascades. the", "cascades. the pathway", "the pathway signaling", "pathway signaling by", "by erbb4 only", "erbb4 only shows", "only shows signaling", "shows signaling by", "by erbb4 homodimers.", "erbb4 homodimers. signaling", "homodimers. signaling by", "signaling by heterodimers", "by heterodimers of", "heterodimers of erbb4", "of erbb4 and", "erbb4 and erbb2", "and erbb2 is", "erbb2 is shown", "is shown in", "shown in the", "in the pathway", "signaling by erbb2.", "by erbb2. ligand", "erbb2. ligand stimulated", "ligand stimulated erbb4", "stimulated erbb4 is", "erbb4 is also", "is also able", "also able to", "able to form", "to form heterodimers", "form heterodimers with", "heterodimers with ligand", "with ligand stimulated", "ligand stimulated egfr", "egfr cohen", "1996 and", "and ligand stimulated", "ligand stimulated erbb3", "erbb3 riese", "et al. 1995", "al. 1995 .", "1995 . dimers", "of erbb4 with", "erbb4 with egfr", "with egfr and", "egfr and dimers", "and dimers of", "erbb4 with erbb3", "with erbb3 were", "erbb3 were demonstrated", "were demonstrated in", "demonstrated in mouse", "in mouse cell", "mouse cell lines", "cell lines in", "lines in which", "in which human", "which human erbb4", "human erbb4 and", "erbb4 and egfr", "and egfr or", "egfr or erbb3", "or erbb3 were", "erbb3 were exogenously", "were exogenously expressed.", "exogenously expressed. these", "expressed. these heterodimers", "these heterodimers undergo", "heterodimers undergo trans", "undergo trans autophosphorylation.", "trans autophosphorylation. the", "autophosphorylation. the promiscuous", "the promiscuous heteromerization", "promiscuous heteromerization of", "heteromerization of erbbs", "of erbbs adds", "erbbs adds combinatorial", "adds combinatorial diversity", "combinatorial diversity to", "diversity to erbb", "to erbb signaling", "erbb signaling processes.", "signaling processes. as", "processes. as erbb4", "as erbb4 binds", "erbb4 binds more", "binds more ligands", "more ligands than", "ligands than other", "than other erbbs", "erbbs but", "but has restricted", "has restricted expression", "expression erbb4", "erbb4 expression channels", "expression channels responses", "channels responses to", "responses to erbb", "to erbb ligands.", "erbb ligands. the", "ligands. the signaling", "the signaling capabilities", "signaling capabilities of", "capabilities of the", "of the four", "the four receptors", "four receptors have", "receptors have been", "have been compared", "compared schulze", "schulze et al.", "et al. 2005", "al. 2005 .

as", "2005 .

as for", ".

as for other", "for other receptor", "other receptor tyrosine", "receptor tyrosine kinases", "kinases erbb4", "erbb4 signaling effectors", "signaling effectors are", "effectors are largely", "are largely dictated", "largely dictated through", "dictated through binding", "through binding of", "binding of effector", "of effector proteins", "effector proteins to", "proteins to erbb4", "to erbb4 peptides", "erbb4 peptides that", "peptides that are", "that are phosphorylated", "are phosphorylated upon", "phosphorylated upon ligand", "upon ligand binding.", "ligand binding. all", "binding. all splicing", "all splicing isoforms", "of erbb4 possess", "erbb4 possess two", "possess two tyrosine", "two tyrosine residues", "c tail that", "tail that serve", "that serve as", "serve as docking", "as docking sites", "docking sites for", "sites for shc1", "shc1 kaushansky", "2008 pinkas", "pinkas kramarski et", "kramarski et al.", "1996 cohen", "al. 1996 .", "1996 . once", ". once bound", "once bound to", "bound to erbb4", "erbb4 shc1", "shc1 becomes phosphorylated", "becomes phosphorylated on", "phosphorylated on tyrosine", "tyrosine residues by", "residues by the", "by the tyrosine", "the tyrosine kinase", "tyrosine kinase activity", "kinase activity of", "activity of erbb4", "erbb4 which", "which enables it", "enables it to", "it to recruit", "to recruit the", "recruit the complex", "the complex of", "complex of grb2", "of grb2 and", "grb2 and sos1", "sos1 resulting", "resulting in the", "in the guanyl", "the guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange on", "exchange on ras", "on ras and", "ras and activation", "and activation of", "activation of raf", "of raf and", "raf and map", "and map kinase", "map kinase cascade", "cascade kainulainen", "kainulainen et al.", "al. 2000 .", "2000 .

the", ".

the cyt1", "

the cyt1 isoforms", "cyt1 isoforms of", "of erbb4 also", "erbb4 also possess", "also possess a", "possess a c", "c tail tyrosine", "tail tyrosine residue", "tyrosine residue that", "that upon", "upon trans autophosphorylation", "autophosphorylation serves", "serves as a", "as a docking", "a docking site", "docking site for", "site for the", "for the p85", "the p85 alpha", "p85 alpha subunit", "alpha subunit of", "subunit of pi3k", "pi3k kaushansky", "2008 cohen", "leading to assembly", "to assembly of", "assembly of an", "of an active", "an active pi3k", "active pi3k complex", "pi3k complex that", "complex that converts", "that converts pip2", "converts pip2 to", "pip2 to pip3", "to pip3 and", "pip3 and activates", "and activates akt", "activates akt signaling", "signaling kainulainen", "2000 .

besides", ".

besides signaling", "

besides signaling as", "signaling as a", "as a conventional", "a conventional transmembrane", "conventional transmembrane receptor", "transmembrane receptor kinase", "kinase erbb4", "erbb4 differs from", "differs from other", "from other erbbs", "other erbbs in", "erbbs in that", "in that jm", "that jm a", "jm a isoforms", "a isoforms signal", "isoforms signal through", "signal through efficient", "through efficient release", "efficient release of", "release of a", "of a soluble", "a soluble intracellular", "soluble intracellular domain.", "intracellular domain. ligand", "domain. ligand activated", "ligand activated homodimers", "activated homodimers of", "homodimers of erbb4", "isoforms erbb4", "a cyt1 and", "cyt1 and erbb4", "cyt2 undergo", "undergo proteolytic cleavage", "proteolytic cleavage by", "cleavage by adam17", "adam17 tace", "tace in", "in the juxtamembrane", "the juxtamembrane region", "region resulting", "resulting in shedding", "in shedding of", "shedding of the", "of the extracellular", "the extracellular domain", "extracellular domain and", "domain and formation", "and formation of", "formation of an", "of an 80", "an 80 kda", "80 kda membrane", "kda membrane bound", "membrane bound erbb4", "bound erbb4 fragment", "erbb4 fragment known", "fragment known as", "known as erbb4", "as erbb4 m80", "m80 rio", "rio et al.", "2000 cheng", "cheng et al.", "et al. 2003", "al. 2003 .", "2003 . erbb4", ". erbb4 m80", "erbb4 m80 undergoes", "m80 undergoes further", "undergoes further proteolytic", "further proteolytic cleavage", "cleavage mediated", "mediated by the", "by the gamma", "the gamma secretase", "gamma secretase complex", "complex which", "which releases the", "releases the soluble", "the soluble 80", "soluble 80 kda", "80 kda erbb4", "kda erbb4 intracellular", "erbb4 intracellular domain", "domain known", "as erbb4 s80", "erbb4 s80 or", "s80 or e4icd", "e4icd into", "into the cytosol", "cytosol ni", "ni et al.", "et al. 2001", "al. 2001 .", "2001 . erbb4", ". erbb4 s80", "erbb4 s80 is", "s80 is able", "is able to", "able to translocate", "to translocate to", "translocate to the", "to the nucleus", "nucleus promote", "promote nuclear translocation", "nuclear translocation of", "translocation of various", "of various transcription", "various transcription factors", "factors and", "and act as", "act as a", "as a transcription", "a transcription co", "transcription co factor.", "co factor. for", "factor. for example", "example in", "in mammary cells", "cells erbb4", "erbb4 binds sh2", "binds sh2 transcription", "sh2 transcription factor", "transcription factor stat5a.", "factor stat5a. erbb4", "stat5a. erbb4 s80", "erbb4 s80 shuttles", "s80 shuttles stat5a", "shuttles stat5a to", "stat5a to the", "and actsa as", "actsa as a", "as a stat5a", "a stat5a co", "stat5a co factor", "co factor in", "factor in binding", "in binding to", "binding to and", "to and promoting", "and promoting transcription", "promoting transcription from", "transcription from the", "from the beta", "the beta casein", "casein csn2", "csn2 promoter", "promoter and", "and may be", "may be involved", "be involved in", "involved in the", "in the regulation", "the regulation of", "regulation of other", "of other lactation", "other lactation related", "lactation related genes", "genes jones", "jones et al.", "et al. 1999", "1999 williams", "williams et al.", "et al. 2004", "2004 muraoka", "muraoka cook et", "cook et al.", "al. 2008 .", "2008 . erbb4", "erbb4 s80 binds", "s80 binds activated", "binds activated estrogen", "activated estrogen receptor", "estrogen receptor in", "receptor in the", "in the nucleus", "the nucleus and", "nucleus and acts", "and acts as", "acts as a", "as a transcriptional", "a transcriptional co", "transcriptional co factor", "factor in promoting", "in promoting transcription", "promoting transcription of", "transcription of some", "of some estrogen", "some estrogen regulated", "estrogen regulated genes", "genes including", "including progesterone receptor", "progesterone receptor gene", "receptor gene nr3c3", "gene nr3c3 and", "nr3c3 and cxcl12", "cxcl12 sdf1", "zhu et al.", "et al. 2006", "al. 2006 .", "2006 . in", ". in neuronal", "in neuronal precursors", "precursors erbb4", "s80 binds the", "binds the complex", "complex of tab", "of tab and", "tab and ncor1", "ncor1 helps", "helps to move", "to move the", "move the complex", "the complex into", "complex into the", "into the nucleus", "and is a", "is a co", "a co factor", "co factor of", "factor of tab:ncor1", "of tab:ncor1 mediated", "tab:ncor1 mediated inhibition", "mediated inhibition of", "inhibition of expression", "of expression of", "expression of astrocyte", "of astrocyte differentiation", "astrocyte differentiation genes", "differentiation genes gfap", "genes gfap and", "gfap and s100b", "s100b sardi", "sardi et al.", "al. 2006 .

the", "2006 .

the c", ".

the c tail", "c tail of", "tail of erbb4", "of erbb4 possesses", "erbb4 possesses several", "possesses several ww", "several ww domain", "ww domain binding", "domain binding motifs", "motifs three", "three in cyt1", "in cyt1 isoform", "cyt1 isoform and", "isoform and two", "and two in", "two in cyt2", "in cyt2 isoform", "which enable interaction", "enable interaction of", "interaction of erbb4", "erbb4 with ww", "with ww domain", "ww domain containing", "domain containing proteins.", "containing proteins. erbb4", "proteins. erbb4 s80", "s80 through", "through ww domain", "motifs interacts", "interacts with yap1", "with yap1 transcription", "yap1 transcription factor", "factor a", "a known proto", "known proto oncogene", "oncogene and", "a co regulator", "co regulator of", "regulator of yap1", "of yap1 mediated", "yap1 mediated transcription", "mediated transcription in", "transcription in association", "in association with", "association with tead", "with tead transcription", "tead transcription factors", "factors komuro", "komuro et al.", "2003 omerovic", "omerovic et al.", "al. 2004 .", "2004 . hence", "hence the", "the ww binding", "ww binding motif", "binding motif couples", "motif couples erbb4", "couples erbb4 to", "erbb4 to the", "to the major", "the major effector", "major effector arm", "effector arm of", "arm of the", "of the hippo", "the hippo signaling", "hippo signaling pathway.", "signaling pathway. the", "pathway. the tumor", "the tumor suppressor", "tumor suppressor wwox", "wwox another", "another ww domain", "domain containing protein", "protein competes", "competes with yap1", "with yap1 in", "yap1 in binding", "binding to erbb4", "to erbb4 s80", "erbb4 s80 and", "s80 and prevents", "and prevents translocation", "prevents translocation of", "translocation of erbb4", "of erbb4 s80", "erbb4 s80 to", "s80 to the", "nucleus aqeilan", "aqeilan et al.", "al. 2005 .

ww", "2005 .

ww domain", ".

ww domain binding", "binding motifs in", "motifs in the", "of erbb4 play", "erbb4 play an", "play an important", "an important role", "important role in", "role in the", "in the downregulation", "the downregulation of", "downregulation of erbb4", "of erbb4 receptor", "erbb4 receptor signaling", "signaling enabling", "enabling the interaction", "the interaction of", "interaction of intact", "of intact erbb4", "erbb4 erbb4", "erbb4 m80 and", "m80 and erbb4", "and erbb4 s80", "erbb4 s80 with", "s80 with nedd4", "with nedd4 family", "nedd4 family of", "family of e3", "of e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases wwp1", "ligases wwp1 and", "wwp1 and itch.", "and itch. the", "itch. the interaction", "interaction of wwp1", "of wwp1 and", "wwp1 and itch", "and itch with", "itch with intact", "with intact erbb4", "intact erbb4 is", "erbb4 is independent", "is independent of", "independent of receptor", "of receptor activation", "receptor activation and", "activation and autophosphorylation.", "and autophosphorylation. binding", "autophosphorylation. binding of", "binding of wwp1", "and itch ubiquitin", "itch ubiquitin ligases", "ubiquitin ligases leads", "ligases leads to", "leads to ubiquitination", "to ubiquitination of", "ubiquitination of erbb4", "erbb4 and its", "and its cleavage", "its cleavage products", "products and", "and subsequent degradation", "subsequent degradation through", "degradation through both", "through both proteasomal", "both proteasomal and", "proteasomal and lysosomal", "and lysosomal routes", "routes omerovic", "2007 feng", "feng et al.", "et al. 2009", "al. 2009 .", "2009 . in", ". in addition", "addition the", "the s80 cleavage", "s80 cleavage product", "cleavage product of", "product of erbb4", "jm a cyt", "a cyt 1", "cyt 1 isoform", "1 isoform is", "isoform is the", "is the target", "the target of", "target of nedd4", "of nedd4 ubiquitin", "nedd4 ubiquitin ligase.", "ubiquitin ligase. nedd4", "ligase. nedd4 binds", "nedd4 binds erbb4", "binds erbb4 jm", "cyt 1 s80", "s80 erbb4jmacyt1s80", "erbb4jmacyt1s80 through", "through its pik3r1", "its pik3r1 interaction", "pik3r1 interaction site", "interaction site and", "site and mediates", "and mediates erbb4jmacyt1s80", "mediates erbb4jmacyt1s80 ubiquitination", "ubiquitination thereby", "thereby decreasing the", "decreasing the amount", "the amount of", "amount of erbb4jmacyt1s80", "of erbb4jmacyt1s80 that", "erbb4jmacyt1s80 that reaches", "that reaches the", "reaches the nucleus", "nucleus zeng", "zeng et al.", "al. 2009 .

erbb4", "2009 .

erbb4 also", ".

erbb4 also binds", "also binds the", "binds the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase mdm2", "mdm2 and", "and inhibitor of", "inhibitor of p53", "p53 arasada", "arasada et al.", "al. 2005 .", "2005 . other", ". other proteins", "other proteins that", "proteins that bind", "that bind to", "bind to erbb4", "to erbb4 intracellular", "intracellular domain have", "domain have been", "have been identified", "been identified by", "identified by co", "by co immunoprecipitation", "co immunoprecipitation and", "immunoprecipitation and mass", "and mass spectrometry", "spectrometry gilmore", "gilmore hebert et", "hebert et al.", "al. 2010", "and include transcriptional", "include transcriptional co", "transcriptional co repressor", "co repressor trim28/kap1", "trim28/kap1 which", "which promotes chromatin", "promotes chromatin compaction.", "chromatin compaction. dna", "compaction. dna damage", "dna damage signaling", "damage signaling through", "signaling through atm", "through atm releases", "atm releases trim28", "releases trim28 associated", "trim28 associated heterochromatinization.", "associated heterochromatinization. interactions", "heterochromatinization. interactions of", "interactions of erbb4", "erbb4 with trim28", "with trim28 and", "trim28 and mdm2", "and mdm2 may", "mdm2 may be", "may be important", "be important for", "important for integration", "for integration of", "integration of growth", "of growth factor", "growth factor responses", "factor responses and", "responses and dna", "and dna damage", "dna damage responses.

in", "damage responses.

in human", "responses.

in human breast", "human breast cancer", "breast cancer cell", "cancer cell lines", "lines erbb4", "erbb4 activation enhances", "activation enhances anchorage", "enhances anchorage independent", "anchorage independent colony", "independent colony formation", "colony formation in", "formation in soft", "in soft agar", "soft agar but", "agar but inhibits", "but inhibits cell", "inhibits cell growth", "cell growth in", "growth in a", "in a monolayer", "a monolayer culture.", "monolayer culture. different", "culture. different erbb4", "different erbb4 ligands", "erbb4 ligands induce", "ligands induce different", "induce different gene", "different gene expression", "gene expression changes", "expression changes in", "changes in breast", "in breast cancer", "cancer cell lines.", "cell lines. some", "lines. some of", "some of the", "of the genes", "the genes induced", "genes induced in", "induced in response", "in response to", "response to erbb4", "to erbb4 signaling", "erbb4 signaling in", "signaling in breast", "cell lines are", "lines are rab2", "rab2 eps15r", "eps15r and gata4.", "and gata4. it", "gata4. it is", "it is not", "is not known", "not known if", "known if these", "if these gene", "these gene are", "gene are direct", "are direct transcriptional", "direct transcriptional targets", "transcriptional targets of", "targets of erbb4", "erbb4 amin", "amin et al.", "al. 2004 .

transcriptome", "2004 .

transcriptome and", ".

transcriptome and chip", "and chip seq", "chip seq comparisons", "seq comparisons of", "comparisons of full", "of full length", "full length and", "length and intracellular", "and intracellular domain", "intracellular domain isoforms", "domain isoforms in", "isoforms in isogenic", "in isogenic mcf10a", "isogenic mcf10a mammary", "mcf10a mammary cell", "mammary cell background", "cell background have", "background have revealed", "have revealed the", "revealed the diversification", "the diversification of", "diversification of erbb4", "of erbb4 signaling", "erbb4 signaling engendered", "signaling engendered by", "engendered by alternative", "by alternative splicing", "alternative splicing and", "splicing and cleavage", "cleavage wali", "wali et al.", "2014 . erbb4", ". erbb4 broadly", "erbb4 broadly affected", "broadly affected protease", "affected protease expression", "expression cholesterol", "biosynthesis hif1", "hif1 alpha signaling", "signaling and", "and hippo signaling", "hippo signaling pathways", "pathways and", "and other pathways", "other pathways were", "pathways were differentially", "were differentially activated", "differentially activated by", "activated by cyt1", "by cyt1 and", "cyt1 and cyt2", "and cyt2 isoforms.", "cyt2 isoforms. for", "isoforms. for example", "example cyt1", "cyt1 promoted expression", "promoted expression of", "expression of transcription", "of transcription factors", "transcription factors twist1", "factors twist1 and", "twist1 and snail1", "and snail1 that", "snail1 that promote", "that promote epithelial", "promote epithelial mesenchymal", "epithelial mesenchymal transition.", "mesenchymal transition. hif1", "transition. hif1 alpha", "hif1 alpha and", "alpha and hippo", "hippo signaling are", "signaling are mediated", "mediated respectively", "respectively by", "by binding of", "binding of erbb4", "of erbb4 to", "erbb4 to hif1", "to hif1 alpha", "alpha and to", "and to yap", "yap paatero", "paatero et al.", "2012 komuro", ". erbb4 increases", "erbb4 increases activity", "increases activity of", "activity of the", "of the transcription", "the transcription factor", "transcription factor srebf2", "srebf2 resulting", "resulting in increased", "in increased expression", "increased expression of", "expression of srebf2", "of srebf2 target", "srebf2 target genes", "target genes involved", "genes involved in", "involved in cholesterol", "in cholesterol biosynthesis.", "cholesterol biosynthesis. the", "biosynthesis. the mechanism", "the mechanism is", "mechanism is not", "not known and", "known and may", "and may involve", "may involve facilitation", "involve facilitation of", "facilitation of srebf2", "of srebf2 cleavage", "srebf2 cleavage through", "cleavage through erbb4", "through erbb4 mediated", "erbb4 mediated pi3k", "mediated pi3k signaling", "signaling haskins", "haskins et al.", "et al. 2016", "al. 2016 .

in", "2016 .

in some", ".

in some contexts", "contexts erbb4", "erbb4 promotes growth", "promotes growth suppression", "growth suppression or", "suppression or apoptosis", "apoptosis penington", "penington et al.", "al. 2002", "2002 . activation", ". activation of", "activation of erbb4", "of erbb4 in", "erbb4 in breast", "cell lines leads", "lines leads to", "leads to jnk", "to jnk dependent", "jnk dependent increase", "dependent increase in", "increase in brca1", "in brca1 mrna", "brca1 mrna level", "mrna level and", "level and mitotic", "and mitotic cell", "mitotic cell cycle", "cell cycle delay", "delay but", "but the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "not been elucidated", "elucidated muraoka", "2006 . the", ". the nature", "the nature of", "nature of growth", "of growth responses", "growth responses may", "responses may be", "may be connected", "be connected with", "connected with the", "with the spliced", "the spliced isoforms", "spliced isoforms expressed.", "isoforms expressed. in", "expressed. in comparisons", "in comparisons of", "comparisons of cyt1", "of cyt1 vs", "cyt1 vs cyt2", "cyt2 full", "length and icd", "icd expression", "expression in mammary", "cells cyt1", "cyt1 was a", "was a weaker", "a weaker growth", "weaker growth inducer", "inducer associated", "associated with attenuated", "with attenuated mapk", "attenuated mapk signaling", "mapk signaling relative", "signaling relative to", "relative to cyt2", "cyt2 wali", "s80 is also", "to the mitochondrial", "the mitochondrial matrix", "matrix presumably", "presumably when its", "when its nuclear", "its nuclear translocation", "nuclear translocation is", "translocation is inhibited.", "is inhibited. once", "inhibited. once in", "once in the", "in the mitochondrion", "mitochondrion the", "the bh3 domain", "bh3 domain of", "domain of erbb4", "erbb4 characteristic", "characteristic of bcl2", "of bcl2 family", "bcl2 family members", "members may", "may enable it", "enable it to", "it to act", "to act as", "as a pro", "a pro apoptotic", "pro apoptotic factor", "factor naresh", "naresh et al.", "al. 2006 .

erbb4", "2006 .

erbb4 plays", ".

erbb4 plays important", "plays important roles", "important roles in", "roles in the", "in the developing", "the developing and", "developing and adult", "and adult nervous", "adult nervous system.", "nervous system. erbb4", "system. erbb4 deficiency", "erbb4 deficiency in", "deficiency in somatostatin", "in somatostatin expressing", "somatostatin expressing neurons", "expressing neurons of", "neurons of the", "of the thalamic", "the thalamic reticular", "thalamic reticular nucleus", "reticular nucleus alters", "nucleus alters behaviors", "alters behaviors dependent", "behaviors dependent on", "dependent on sensory", "on sensory selection", "selection ahrens", "ahrens et al.", "et al. 2015", "al. 2015 .", "2015 . nrg1", ". nrg1 activated", "nrg1 activated erbb4", "activated erbb4 signaling", "erbb4 signaling enhances", "signaling enhances ampa", "enhances ampa receptor", "ampa receptor responses", "receptor responses through", "responses through pkc", "through pkc dependent", "pkc dependent ampa", "dependent ampa receptor", "ampa receptor exocytosis.", "receptor exocytosis. this", "exocytosis. this results", "this results in", "results in an", "in an increased", "an increased excitatory", "increased excitatory input", "excitatory input to", "input to parvalbumin", "to parvalbumin expressing", "parvalbumin expressing inhibitory", "expressing inhibitory neurons", "inhibitory neurons in", "neurons in the", "in the visual", "the visual cortex", "visual cortex and", "cortex and regulates", "and regulates visual", "regulates visual cortical", "visual cortical plasticity", "plasticity sun", "sun et al.", "al. 2016 .", "2016 . nrg1", "erbb4 signaling is", "signaling is involved", "is involved in", "involved in gabaergic", "in gabaergic activity", "gabaergic activity in", "activity in amygdala", "in amygdala which", "amygdala which mediates", "which mediates fear", "mediates fear conditioning", "conditioning fear", "lu et al.", "et al. 2014", "al. 2014 .", "2014 . conditional", ". conditional erbb4", "conditional erbb4 deletion", "erbb4 deletion from", "deletion from fast", "from fast spiking", "fast spiking interneurons", "interneurons chandelier", "chandelier and basket", "and basket cells", "basket cells of", "cells of the", "of the cerebral", "the cerebral cortex", "cerebral cortex leads", "cortex leads to", "leads to synaptic", "to synaptic defects", "synaptic defects associated", "defects associated with", "associated with increased", "with increased locomotor", "increased locomotor activity", "locomotor activity and", "activity and abnormal", "and abnormal emotional", "emotional social", "social and cognitive", "and cognitive function", "cognitive function that", "function that can", "that can be", "can be linked", "be linked to", "linked to some", "to some of", "of the schizophrenia", "the schizophrenia features.", "schizophrenia features. the", "features. the level", "the level of", "level of gad1", "gad1 gad67", "gad67 protein", "protein is reduced", "is reduced in", "reduced in the", "in the cortex", "the cortex of", "cortex of conditional", "of conditional erbb4", "conditional erbb4 mutants.", "erbb4 mutants. gad1", "mutants. gad1 is", "gad1 is a", "is a gaba", "a gaba synthesizing", "gaba synthesizing enzyme.", "synthesizing enzyme. cortical", "enzyme. cortical mrna", "cortical mrna levels", "mrna levels of", "levels of gad67", "of gad67 are", "gad67 are consistently", "are consistently decreased", "consistently decreased in", "decreased in schizophrenia", "schizophrenia del", "del pino et", "pino et al.", ". erbb4 is", "erbb4 is expressed", "is expressed in", "expressed in the", "in the gabaergic", "the gabaergic neurons", "gabaergic neurons of", "of the bed", "the bed nucleus", "bed nucleus stria", "nucleus stria terminalis", "terminalis a", "a part of", "part of the", "of the extended", "the extended amygdala.", "extended amygdala. inhibition", "amygdala. inhibition of", "inhibition of nrg1", "of nrg1 triggered", "nrg1 triggered erbb4", "triggered erbb4 signaling", "erbb4 signaling induces", "signaling induces anxiety", "induces anxiety like", "anxiety like behavior", "behavior which", "which depends on", "depends on gabaergic", "on gabaergic neurotransmission.", "gabaergic neurotransmission. nrg1", "neurotransmission. nrg1 erbb4", "nrg1 erbb4 signaling", "erbb4 signaling stimulates", "signaling stimulates presynaptic", "stimulates presynaptic gaba", "presynaptic gaba release", "release but", "exact mechanism is", "known geng", "geng et al.", ". nrg1 protects", "nrg1 protects cortical", "protects cortical interneurons", "cortical interneurons against", "interneurons against ischemic", "against ischemic brain", "ischemic brain injury", "brain injury through", "injury through erbb4", "erbb4 mediated increase", "mediated increase in", "increase in gabaergic", "in gabaergic transmission", "transmission guan", "guan et al.", "2015 . nrg2", ". nrg2 activated", "nrg2 activated erbb4", "activated erbb4 can", "erbb4 can reduce", "can reduce the", "reduce the duration", "the duration of", "duration of gabaergic", "of gabaergic transmission", "gabaergic transmission by", "transmission by binding", "by binding to", "binding to gaba", "to gaba receptors", "gaba receptors at", "receptors at the", "at the postsynaptic", "the postsynaptic membrane", "postsynaptic membrane via", "membrane via their", "via their gabra1", "their gabra1 subunit", "gabra1 subunit and", "subunit and promoting", "and promoting endocytosis", "promoting endocytosis of", "endocytosis of gaba", "of gaba receptors", "receptors mitchell", "mitchell et al.", "et al. 2013", "al. 2013 .", "2013 . nrg1", ". nrg1 promotes", "nrg1 promotes synchronization", "promotes synchronization of", "synchronization of prefrontal", "of prefrontal cortex", "prefrontal cortex interneurons", "cortex interneurons in", "interneurons in an", "in an erbb4", "an erbb4 dependent", "erbb4 dependent manner", "manner hou", "hou et al.", "2014 . nrg1", ". nrg1 erbb4", "erbb4 signaling protects", "signaling protects neurons", "protects neurons from", "neurons from the", "from the cell", "the cell death", "cell death induced", "death induced by", "induced by a", "by a mutant", "a mutant form", "mutant form of", "form of the", "of the amyloid", "the amyloid precursor", "amyloid precursor protein", "protein app", "woo et al.", "et al. 2012", "al. 2012 .

clinical", "2012 .

clinical relevance", ".

clinical relevance of", "relevance of erbb4", "of erbb4 has", "erbb4 has been", "has been identified", "been identified in", "identified in several", "in several contexts.", "several contexts. in", "contexts. in cancer", "cancer putative", "putative and validated", "and validated gain", "validated gain of", "gain of function", "of function mutations", "function mutations or", "mutations or gene", "or gene amplification", "gene amplification that", "amplification that may", "that may be", "may be drivers", "be drivers have", "drivers have been", "been identified at", "identified at modest", "at modest frequencies", "frequencies and", "and may also", "may also contribute", "also contribute to", "contribute to resistance", "to resistance to", "resistance to egfr", "to egfr and", "egfr and erbb2", "and erbb2 targeted", "erbb2 targeted therapies.", "targeted therapies. this", "therapies. this is", "this is noteworthy", "is noteworthy as", "noteworthy as erbb4", "as erbb4 kinase", "erbb4 kinase activity", "kinase activity is", "activity is inhibited", "is inhibited by", "inhibited by pan", "by pan erbb", "pan erbb tyrosine", "erbb tyrosine kinase", "tyrosine kinase inhibitors", "inhibitors including", "lapatinib which", "which is approved", "is approved by", "approved by the", "by the us", "the us fda.", "us fda. the", "fda. the reduced", "the reduced prevalence", "reduced prevalence relative", "prevalence relative to", "relative to egfr", "and erbb2 in", "erbb2 in cancer", "in cancer may", "cancer may reflect", "may reflect more", "reflect more restricted", "more restricted expression", "restricted expression of", "expression of erbb4", "erbb4 or", "or differential signaling", "as specific erbb4", "specific erbb4 isoforms", "erbb4 isoforms have", "isoforms have been", "have been linked", "been linked to", "linked to growth", "to growth inhibition", "growth inhibition or", "inhibition or apoptosis", "or apoptosis in", "apoptosis in experimental", "in experimental systems.", "experimental systems. erbb2/erbb4", "systems. erbb2/erbb4 heterodimers", "erbb2/erbb4 heterodimers protect", "heterodimers protect cardiomyocytes", "cardiomyocytes so", "so reduced activity", "reduced activity of", "erbb4 in patients", "in patients treated", "patients treated with", "treated with the", "with the erbb2", "the erbb2 targeted", "erbb2 targeted therapeutic", "targeted therapeutic antibody", "therapeutic antibody trastuzumab", "antibody trastuzumab may", "trastuzumab may contribute", "may contribute to", "contribute to the", "to the cardiotoxicity", "the cardiotoxicity of", "cardiotoxicity of this", "of this agent", "this agent when", "agent when used", "when used in", "used in combination", "in combination with", "with cardiotoxic", "cardiotoxic anthracyclines.

with", "anthracyclines.

with the importance", "the importance of", "importance of erbb4", "erbb4 in developing", "in developing and", "adult nervous system", "system nrg1", "nrg1 and/or erbb4", "and/or erbb4 polymorphisms", "polymorphisms splicing", "splicing aberrations and", "aberrations and mutations", "and mutations have", "mutations have been", "linked to nervous", "to nervous system", "nervous system disorders", "system disorders including", "disorders including schizophrenia", "including schizophrenia and", "schizophrenia and amyotrophic", "and amyotrophic lateral", "amyotrophic lateral sclerosis", "sclerosis although", "although these findings", "these findings are", "findings are not", "are not yet", "not yet definitive.", "erbb4 also known", "also known as her4", "as her4 belongs", "her4 belongs to", "belongs to the erbb", "to the erbb family", "the erbb family of", "erbb family of receptors", "of receptors which", "receptors which also", "which also includes erbb1", "includes erbb1 egfr/her1", "egfr/her1 erbb2", "her2/neu and erbb3", "and erbb3 her3", "erbb3 her3 .", "her3 . similar to", ". similar to egfr", "to egfr erbb4", "egfr erbb4 has", "erbb4 has an extracellular", "has an extracellular ligand", "an extracellular ligand binding", "extracellular ligand binding domain", "binding domain a", "domain a single", "a single transmembrane domain", "single transmembrane domain and", "transmembrane domain and a", "domain and a cytoplasmic", "and a cytoplasmic domain", "a cytoplasmic domain which", "cytoplasmic domain which contains", "domain which contains an", "which contains an active", "contains an active tyrosine", "an active tyrosine kinase", "active tyrosine kinase and", "tyrosine kinase and a", "kinase and a c", "and a c tail", "a c tail with", "c tail with multiple", "tail with multiple phosphorylation", "with multiple phosphorylation sites.", "multiple phosphorylation sites. at", "phosphorylation sites. at least", "sites. at least three", "at least three and", "least three and possibly", "three and possibly four", "and possibly four splicing", "possibly four splicing isoforms", "four splicing isoforms of", "splicing isoforms of erbb4", "isoforms of erbb4 exist", "of erbb4 exist that", "erbb4 exist that differ", "exist that differ in", "that differ in their", "differ in their c", "in their c tail", "their c tail and/or", "c tail and/or the", "tail and/or the extracellular", "and/or the extracellular juxtamembrane", "the extracellular juxtamembrane regions:", "extracellular juxtamembrane regions: erbb4", "juxtamembrane regions: erbb4 jm", "regions: erbb4 jm a", "erbb4 jm a cyt1", "a cyt1 erbb4", "cyt1 erbb4 jm", "erbb4 jm a cyt2", "jm a cyt2 and", "a cyt2 and erbb4", "cyt2 and erbb4 jm", "and erbb4 jm b", "erbb4 jm b cyt1", "b cyt1 the", "cyt1 the existence", "the existence of erbb4", "existence of erbb4 jm", "of erbb4 jm b", "erbb4 jm b cyt2", "jm b cyt2 has", "b cyt2 has not", "cyt2 has not been", "has not been confirmed", "not been confirmed .", "been confirmed .

erbb4", "confirmed .

erbb4 becomes", ".

erbb4 becomes activated", "

erbb4 becomes activated by", "becomes activated by binding", "activated by binding one", "by binding one of", "binding one of its", "one of its seven", "of its seven ligands", "seven ligands three", "ligands three of", "of which hb", "which hb egf", "hb egf epiregulin", "egf epiregulin epr", "epiregulin epr and betacellulin", "epr and betacellulin btc", "betacellulin btc are", "btc are egf", "egf like elenius", "like elenius et", "elenius et al. 1997", "al. 1997 riese", "1997 riese et", "riese et al. 1998", "1998 while", "while four nrg1", "nrg2 nrg3 and", "and nrg4 belong", "nrg4 belong to", "belong to the related", "to the related neuregulin", "the related neuregulin family", "neuregulin family tzahar", "family tzahar et", "tzahar et al. 1994", "al. 1994 carraway", "1994 carraway et", "carraway et al. 1997", "al. 1997 zhang", "1997 zhang et", "zhang et al. 1997", "al. 1997 hayes", "1997 hayes et", "hayes et al. 2007", "et al. 2007 .", "al. 2007 . upon", "2007 . upon ligand", ". upon ligand binding", "ligand binding erbb4", "binding erbb4 forms", "forms homodimers sweeney", "homodimers sweeney et", "sweeney et al. 2000", "al. 2000 or", "2000 or it", "or it heterodimerizes with", "it heterodimerizes with erbb2", "with erbb2 li", "erbb2 li et", "li et al. 2007", "al. 2007 . dimers", "2007 . dimers of", ". dimers of erbb4", "dimers of erbb4 undergo", "of erbb4 undergo trans", "erbb4 undergo trans autophosphorylation", "undergo trans autophosphorylation on", "trans autophosphorylation on tyrosine", "autophosphorylation on tyrosine residues", "on tyrosine residues in", "tyrosine residues in the", "residues in the c", "in the c tail", "c tail cohen", "tail cohen et", "cohen et al. 1996", "al. 1996 kaushansky", "1996 kaushansky et", "kaushansky et al. 2008", "al. 2008 hazan", "2008 hazan et", "hazan et al. 1990", "al. 1990 li", "1990 li et", "2007 triggering", "triggering downstream signaling cascades.", "downstream signaling cascades. the", "signaling cascades. the pathway", "cascades. the pathway signaling", "the pathway signaling by", "pathway signaling by erbb4", "signaling by erbb4 only", "by erbb4 only shows", "erbb4 only shows signaling", "only shows signaling by", "shows signaling by erbb4", "signaling by erbb4 homodimers.", "by erbb4 homodimers. signaling", "erbb4 homodimers. signaling by", "homodimers. signaling by heterodimers", "signaling by heterodimers of", "by heterodimers of erbb4", "heterodimers of erbb4 and", "of erbb4 and erbb2", "erbb4 and erbb2 is", "and erbb2 is shown", "erbb2 is shown in", "is shown in the", "shown in the pathway", "in the pathway signaling", "pathway signaling by erbb2.", "signaling by erbb2. ligand", "by erbb2. ligand stimulated", "erbb2. ligand stimulated erbb4", "ligand stimulated erbb4 is", "stimulated erbb4 is also", "erbb4 is also able", "is also able to", "also able to form", "able to form heterodimers", "to form heterodimers with", "form heterodimers with ligand", "heterodimers with ligand stimulated", "with ligand stimulated egfr", "stimulated egfr cohen", "egfr cohen et", "al. 1996 and", "1996 and ligand", "and ligand stimulated erbb3", "stimulated erbb3 riese", "erbb3 riese et", "riese et al. 1995", "et al. 1995 .", "al. 1995 . dimers", "1995 . dimers of", "dimers of erbb4 with", "of erbb4 with egfr", "erbb4 with egfr and", "with egfr and dimers", "egfr and dimers of", "and dimers of erbb4", "of erbb4 with erbb3", "erbb4 with erbb3 were", "with erbb3 were demonstrated", "erbb3 were demonstrated in", "were demonstrated in mouse", "demonstrated in mouse cell", "in mouse cell lines", "mouse cell lines in", "cell lines in which", "lines in which human", "in which human erbb4", "which human erbb4 and", "human erbb4 and egfr", "erbb4 and egfr or", "and egfr or erbb3", "egfr or erbb3 were", "or erbb3 were exogenously", "erbb3 were exogenously expressed.", "were exogenously expressed. these", "exogenously expressed. these heterodimers", "expressed. these heterodimers undergo", "these heterodimers undergo trans", "heterodimers undergo trans autophosphorylation.", "undergo trans autophosphorylation. the", "trans autophosphorylation. the promiscuous", "autophosphorylation. the promiscuous heteromerization", "the promiscuous heteromerization of", "promiscuous heteromerization of erbbs", "heteromerization of erbbs adds", "of erbbs adds combinatorial", "erbbs adds combinatorial diversity", "adds combinatorial diversity to", "combinatorial diversity to erbb", "diversity to erbb signaling", "to erbb signaling processes.", "erbb signaling processes. as", "signaling processes. as erbb4", "processes. as erbb4 binds", "as erbb4 binds more", "erbb4 binds more ligands", "binds more ligands than", "more ligands than other", "ligands than other erbbs", "other erbbs but", "erbbs but has", "but has restricted expression", "restricted expression erbb4", "expression erbb4 expression", "erbb4 expression channels responses", "expression channels responses to", "channels responses to erbb", "responses to erbb ligands.", "to erbb ligands. the", "erbb ligands. the signaling", "ligands. the signaling capabilities", "the signaling capabilities of", "signaling capabilities of the", "capabilities of the four", "of the four receptors", "the four receptors have", "four receptors have been", "receptors have been compared", "been compared schulze", "compared schulze et", "schulze et al. 2005", "et al. 2005 .

as", "al. 2005 .

as for", "2005 .

as for other", ".

as for other receptor", "for other receptor tyrosine", "other receptor tyrosine kinases", "tyrosine kinases erbb4", "kinases erbb4 signaling", "erbb4 signaling effectors are", "signaling effectors are largely", "effectors are largely dictated", "are largely dictated through", "largely dictated through binding", "dictated through binding of", "through binding of effector", "binding of effector proteins", "of effector proteins to", "effector proteins to erbb4", "proteins to erbb4 peptides", "to erbb4 peptides that", "erbb4 peptides that are", "peptides that are phosphorylated", "that are phosphorylated upon", "are phosphorylated upon ligand", "phosphorylated upon ligand binding.", "upon ligand binding. all", "ligand binding. all splicing", "binding. all splicing isoforms", "all splicing isoforms of", "isoforms of erbb4 possess", "of erbb4 possess two", "erbb4 possess two tyrosine", "possess two tyrosine residues", "two tyrosine residues in", "the c tail that", "c tail that serve", "tail that serve as", "that serve as docking", "serve as docking sites", "as docking sites for", "docking sites for shc1", "for shc1 kaushansky", "shc1 kaushansky et", "al. 2008 pinkas", "2008 pinkas kramarski", "pinkas kramarski et al.", "kramarski et al. 1996", "al. 1996 cohen", "1996 cohen et", "et al. 1996 .", "al. 1996 . once", "1996 . once bound", ". once bound to", "once bound to erbb4", "to erbb4 shc1", "erbb4 shc1 becomes", "shc1 becomes phosphorylated on", "becomes phosphorylated on tyrosine", "phosphorylated on tyrosine residues", "on tyrosine residues by", "tyrosine residues by the", "residues by the tyrosine", "by the tyrosine kinase", "the tyrosine kinase activity", "tyrosine kinase activity of", "kinase activity of erbb4", "of erbb4 which", "erbb4 which enables", "which enables it to", "enables it to recruit", "it to recruit the", "to recruit the complex", "recruit the complex of", "the complex of grb2", "complex of grb2 and", "of grb2 and sos1", "and sos1 resulting", "sos1 resulting in", "resulting in the guanyl", "in the guanyl nucleotide", "the guanyl nucleotide exchange", "guanyl nucleotide exchange on", "nucleotide exchange on ras", "exchange on ras and", "on ras and activation", "ras and activation of", "and activation of raf", "activation of raf and", "of raf and map", "raf and map kinase", "and map kinase cascade", "kinase cascade kainulainen", "cascade kainulainen et", "kainulainen et al. 2000", "et al. 2000 .", "al. 2000 .

the", "2000 .

the cyt1", ".

the cyt1 isoforms", "

the cyt1 isoforms of", "cyt1 isoforms of erbb4", "isoforms of erbb4 also", "of erbb4 also possess", "erbb4 also possess a", "also possess a c", "possess a c tail", "a c tail tyrosine", "c tail tyrosine residue", "tail tyrosine residue that", "residue that upon", "that upon trans", "trans autophosphorylation serves", "autophosphorylation serves as", "serves as a docking", "as a docking site", "a docking site for", "docking site for the", "site for the p85", "for the p85 alpha", "the p85 alpha subunit", "p85 alpha subunit of", "alpha subunit of pi3k", "of pi3k kaushansky", "pi3k kaushansky et", "al. 2008 cohen", "2008 cohen et", "1996 leading", "leading to assembly of", "to assembly of an", "assembly of an active", "of an active pi3k", "an active pi3k complex", "active pi3k complex that", "pi3k complex that converts", "complex that converts pip2", "that converts pip2 to", "converts pip2 to pip3", "pip2 to pip3 and", "to pip3 and activates", "pip3 and activates akt", "and activates akt signaling", "akt signaling kainulainen", "signaling kainulainen et", "al. 2000 .

besides", "2000 .

besides signaling", ".

besides signaling as", "

besides signaling as a", "signaling as a conventional", "as a conventional transmembrane", "a conventional transmembrane receptor", "conventional transmembrane receptor kinase", "receptor kinase erbb4", "kinase erbb4 differs", "erbb4 differs from other", "differs from other erbbs", "from other erbbs in", "other erbbs in that", "erbbs in that jm", "in that jm a", "that jm a isoforms", "jm a isoforms signal", "a isoforms signal through", "isoforms signal through efficient", "signal through efficient release", "through efficient release of", "efficient release of a", "release of a soluble", "of a soluble intracellular", "a soluble intracellular domain.", "soluble intracellular domain. ligand", "intracellular domain. ligand activated", "domain. ligand activated homodimers", "ligand activated homodimers of", "activated homodimers of erbb4", "homodimers of erbb4 jm", "of erbb4 jm a", "erbb4 jm a isoforms", "a isoforms erbb4", "isoforms erbb4 jm", "jm a cyt1 and", "a cyt1 and erbb4", "cyt1 and erbb4 jm", "and erbb4 jm a", "a cyt2 undergo", "cyt2 undergo proteolytic", "undergo proteolytic cleavage by", "proteolytic cleavage by adam17", "by adam17 tace", "tace in the", "in the juxtamembrane region", "juxtamembrane region resulting", "region resulting in", "resulting in shedding of", "in shedding of the", "shedding of the extracellular", "of the extracellular domain", "the extracellular domain and", "extracellular domain and formation", "domain and formation of", "and formation of an", "formation of an 80", "of an 80 kda", "an 80 kda membrane", "80 kda membrane bound", "kda membrane bound erbb4", "membrane bound erbb4 fragment", "bound erbb4 fragment known", "erbb4 fragment known as", "fragment known as erbb4", "known as erbb4 m80", "erbb4 m80 rio", "m80 rio et", "rio et al. 2000", "al. 2000 cheng", "2000 cheng et", "cheng et al. 2003", "et al. 2003 .", "al. 2003 . erbb4", "2003 . erbb4 m80", ". erbb4 m80 undergoes", "erbb4 m80 undergoes further", "m80 undergoes further proteolytic", "undergoes further proteolytic cleavage", "proteolytic cleavage mediated", "cleavage mediated by", "mediated by the gamma", "by the gamma secretase", "the gamma secretase complex", "secretase complex which", "complex which releases", "which releases the soluble", "releases the soluble 80", "the soluble 80 kda", "soluble 80 kda erbb4", "80 kda erbb4 intracellular", "kda erbb4 intracellular domain", "intracellular domain known", "domain known as", "known as erbb4 s80", "as erbb4 s80 or", "erbb4 s80 or e4icd", "or e4icd into", "e4icd into the", "the cytosol ni", "cytosol ni et", "ni et al. 2001", "et al. 2001 .", "al. 2001 . erbb4", "2001 . erbb4 s80", ". erbb4 s80 is", "erbb4 s80 is able", "s80 is able to", "is able to translocate", "able to translocate to", "to translocate to the", "translocate to the nucleus", "the nucleus promote", "nucleus promote nuclear", "promote nuclear translocation of", "nuclear translocation of various", "translocation of various transcription", "of various transcription factors", "transcription factors and", "factors and act", "and act as a", "act as a transcription", "as a transcription co", "a transcription co factor.", "transcription co factor. for", "co factor. for example", "for example in", "example in mammary", "mammary cells erbb4", "cells erbb4 binds", "erbb4 binds sh2 transcription", "binds sh2 transcription factor", "sh2 transcription factor stat5a.", "transcription factor stat5a. erbb4", "factor stat5a. erbb4 s80", "stat5a. erbb4 s80 shuttles", "erbb4 s80 shuttles stat5a", "s80 shuttles stat5a to", "shuttles stat5a to the", "stat5a to the nucleus", "nucleus and actsa", "and actsa as a", "actsa as a stat5a", "as a stat5a co", "a stat5a co factor", "stat5a co factor in", "co factor in binding", "factor in binding to", "in binding to and", "binding to and promoting", "to and promoting transcription", "and promoting transcription from", "promoting transcription from the", "transcription from the beta", "from the beta casein", "beta casein csn2", "promoter and may", "and may be involved", "may be involved in", "be involved in the", "involved in the regulation", "in the regulation of", "the regulation of other", "regulation of other lactation", "of other lactation related", "other lactation related genes", "related genes jones", "genes jones et", "jones et al. 1999", "al. 1999 williams", "1999 williams et", "williams et al. 2004", "al. 2004 muraoka", "2004 muraoka cook", "muraoka cook et al.", "cook et al. 2008", "et al. 2008 .", "al. 2008 . erbb4", "2008 . erbb4 s80", ". erbb4 s80 binds", "erbb4 s80 binds activated", "s80 binds activated estrogen", "binds activated estrogen receptor", "activated estrogen receptor in", "estrogen receptor in the", "receptor in the nucleus", "in the nucleus and", "the nucleus and acts", "nucleus and acts as", "and acts as a", "acts as a transcriptional", "as a transcriptional co", "a transcriptional co factor", "transcriptional co factor in", "co factor in promoting", "factor in promoting transcription", "in promoting transcription of", "promoting transcription of some", "transcription of some estrogen", "of some estrogen regulated", "some estrogen regulated genes", "regulated genes including", "genes including progesterone", "including progesterone receptor gene", "progesterone receptor gene nr3c3", "receptor gene nr3c3 and", "gene nr3c3 and cxcl12", "and cxcl12 sdf1", "sdf1 zhu", "zhu et al. 2006", "et al. 2006 .", "al. 2006 . in", "2006 . in neuronal", ". in neuronal precursors", "neuronal precursors erbb4", "precursors erbb4 s80", "erbb4 s80 binds the", "s80 binds the complex", "binds the complex of", "the complex of tab", "complex of tab and", "of tab and ncor1", "and ncor1 helps", "ncor1 helps to", "helps to move the", "to move the complex", "move the complex into", "the complex into the", "complex into the nucleus", "nucleus and is", "and is a co", "is a co factor", "a co factor of", "co factor of tab:ncor1", "factor of tab:ncor1 mediated", "of tab:ncor1 mediated inhibition", "tab:ncor1 mediated inhibition of", "mediated inhibition of expression", "inhibition of expression of", "of expression of astrocyte", "expression of astrocyte differentiation", "of astrocyte differentiation genes", "astrocyte differentiation genes gfap", "differentiation genes gfap and", "genes gfap and s100b", "and s100b sardi", "s100b sardi et", "sardi et al. 2006", "et al. 2006 .

the", "al. 2006 .

the c", "2006 .

the c tail", ".

the c tail of", "c tail of erbb4", "tail of erbb4 possesses", "of erbb4 possesses several", "erbb4 possesses several ww", "possesses several ww domain", "several ww domain binding", "ww domain binding motifs", "binding motifs three", "motifs three in", "three in cyt1 isoform", "in cyt1 isoform and", "cyt1 isoform and two", "isoform and two in", "and two in cyt2", "two in cyt2 isoform", "isoform which", "which enable interaction of", "enable interaction of erbb4", "interaction of erbb4 with", "of erbb4 with ww", "erbb4 with ww domain", "with ww domain containing", "ww domain containing proteins.", "domain containing proteins. erbb4", "containing proteins. erbb4 s80", "erbb4 s80 through", "s80 through ww", "through ww domain binding", "binding motifs interacts", "motifs interacts with", "interacts with yap1 transcription", "with yap1 transcription factor", "transcription factor a", "factor a known", "a known proto oncogene", "proto oncogene and", "oncogene and is", "is a co regulator", "a co regulator of", "co regulator of yap1", "regulator of yap1 mediated", "of yap1 mediated transcription", "yap1 mediated transcription in", "mediated transcription in association", "transcription in association with", "in association with tead", "association with tead transcription", "with tead transcription factors", "transcription factors komuro", "factors komuro et", "komuro et al. 2003", "al. 2003 omerovic", "2003 omerovic et", "omerovic et al. 2004", "et al. 2004 .", "al. 2004 . hence", ". hence the", "hence the ww", "the ww binding motif", "ww binding motif couples", "binding motif couples erbb4", "motif couples erbb4 to", "couples erbb4 to the", "erbb4 to the major", "to the major effector", "the major effector arm", "major effector arm of", "effector arm of the", "arm of the hippo", "of the hippo signaling", "the hippo signaling pathway.", "hippo signaling pathway. the", "signaling pathway. the tumor", "pathway. the tumor suppressor", "the tumor suppressor wwox", "suppressor wwox another", "wwox another ww", "another ww domain containing", "ww domain containing protein", "containing protein competes", "protein competes with", "competes with yap1 in", "with yap1 in binding", "yap1 in binding to", "in binding to erbb4", "binding to erbb4 s80", "to erbb4 s80 and", "erbb4 s80 and prevents", "s80 and prevents translocation", "and prevents translocation of", "prevents translocation of erbb4", "translocation of erbb4 s80", "of erbb4 s80 to", "erbb4 s80 to the", "s80 to the nucleus", "the nucleus aqeilan", "nucleus aqeilan et", "aqeilan et al. 2005", "et al. 2005 .

ww", "al. 2005 .

ww domain", "2005 .

ww domain binding", ".

ww domain binding motifs", "domain binding motifs in", "binding motifs in the", "motifs in the c", "the c tail of", "tail of erbb4 play", "of erbb4 play an", "erbb4 play an important", "play an important role", "an important role in", "important role in the", "role in the downregulation", "in the downregulation of", "the downregulation of erbb4", "downregulation of erbb4 receptor", "of erbb4 receptor signaling", "receptor signaling enabling", "signaling enabling the", "enabling the interaction of", "the interaction of intact", "interaction of intact erbb4", "intact erbb4 erbb4", "erbb4 erbb4 m80", "erbb4 m80 and erbb4", "m80 and erbb4 s80", "and erbb4 s80 with", "erbb4 s80 with nedd4", "s80 with nedd4 family", "with nedd4 family of", "nedd4 family of e3", "family of e3 ubiquitin", "of e3 ubiquitin ligases", "e3 ubiquitin ligases wwp1", "ubiquitin ligases wwp1 and", "ligases wwp1 and itch.", "wwp1 and itch. the", "and itch. the interaction", "itch. the interaction of", "the interaction of wwp1", "interaction of wwp1 and", "of wwp1 and itch", "wwp1 and itch with", "and itch with intact", "itch with intact erbb4", "with intact erbb4 is", "intact erbb4 is independent", "erbb4 is independent of", "is independent of receptor", "independent of receptor activation", "of receptor activation and", "receptor activation and autophosphorylation.", "activation and autophosphorylation. binding", "and autophosphorylation. binding of", "autophosphorylation. binding of wwp1", "binding of wwp1 and", "wwp1 and itch ubiquitin", "and itch ubiquitin ligases", "itch ubiquitin ligases leads", "ubiquitin ligases leads to", "ligases leads to ubiquitination", "leads to ubiquitination of", "to ubiquitination of erbb4", "ubiquitination of erbb4 and", "of erbb4 and its", "erbb4 and its cleavage", "and its cleavage products", "cleavage products and", "products and subsequent", "and subsequent degradation through", "subsequent degradation through both", "degradation through both proteasomal", "through both proteasomal and", "both proteasomal and lysosomal", "proteasomal and lysosomal routes", "lysosomal routes omerovic", "routes omerovic et", "omerovic et al. 2007", "al. 2007 feng", "2007 feng et", "feng et al. 2009", "et al. 2009 .", "al. 2009 . in", "2009 . in addition", "in addition the", "addition the s80", "the s80 cleavage product", "s80 cleavage product of", "cleavage product of erbb4", "product of erbb4 jm", "erbb4 jm a cyt", "jm a cyt 1", "a cyt 1 isoform", "cyt 1 isoform is", "1 isoform is the", "isoform is the target", "is the target of", "the target of nedd4", "target of nedd4 ubiquitin", "of nedd4 ubiquitin ligase.", "nedd4 ubiquitin ligase. nedd4", "ubiquitin ligase. nedd4 binds", "ligase. nedd4 binds erbb4", "nedd4 binds erbb4 jm", "binds erbb4 jm a", "a cyt 1 s80", "1 s80 erbb4jmacyt1s80", "erbb4jmacyt1s80 through its", "through its pik3r1 interaction", "its pik3r1 interaction site", "pik3r1 interaction site and", "interaction site and mediates", "site and mediates erbb4jmacyt1s80", "and mediates erbb4jmacyt1s80 ubiquitination", "erbb4jmacyt1s80 ubiquitination thereby", "ubiquitination thereby decreasing", "thereby decreasing the amount", "decreasing the amount of", "the amount of erbb4jmacyt1s80", "amount of erbb4jmacyt1s80 that", "of erbb4jmacyt1s80 that reaches", "erbb4jmacyt1s80 that reaches the", "that reaches the nucleus", "the nucleus zeng", "nucleus zeng et", "zeng et al. 2009", "et al. 2009 .

erbb4", "al. 2009 .

erbb4 also", "2009 .

erbb4 also binds", ".

erbb4 also binds the", "also binds the e3", "binds the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase mdm2", "ligase mdm2 and", "mdm2 and inhibitor", "and inhibitor of p53", "of p53 arasada", "p53 arasada et", "arasada et al. 2005", "et al. 2005 .", "al. 2005 . other", "2005 . other proteins", ". other proteins that", "other proteins that bind", "proteins that bind to", "that bind to erbb4", "bind to erbb4 intracellular", "to erbb4 intracellular domain", "erbb4 intracellular domain have", "intracellular domain have been", "domain have been identified", "have been identified by", "been identified by co", "identified by co immunoprecipitation", "by co immunoprecipitation and", "co immunoprecipitation and mass", "immunoprecipitation and mass spectrometry", "mass spectrometry gilmore", "spectrometry gilmore hebert", "gilmore hebert et al.", "et al. 2010", "2010 and", "and include transcriptional co", "include transcriptional co repressor", "transcriptional co repressor trim28/kap1", "repressor trim28/kap1 which", "trim28/kap1 which promotes", "which promotes chromatin compaction.", "promotes chromatin compaction. dna", "chromatin compaction. dna damage", "compaction. dna damage signaling", "dna damage signaling through", "damage signaling through atm", "signaling through atm releases", "through atm releases trim28", "atm releases trim28 associated", "releases trim28 associated heterochromatinization.", "trim28 associated heterochromatinization. interactions", "associated heterochromatinization. interactions of", "heterochromatinization. interactions of erbb4", "interactions of erbb4 with", "of erbb4 with trim28", "erbb4 with trim28 and", "with trim28 and mdm2", "trim28 and mdm2 may", "and mdm2 may be", "mdm2 may be important", "may be important for", "be important for integration", "important for integration of", "for integration of growth", "integration of growth factor", "of growth factor responses", "growth factor responses and", "factor responses and dna", "responses and dna damage", "and dna damage responses.

in", "dna damage responses.

in human", "damage responses.

in human breast", "responses.

in human breast cancer", "human breast cancer cell", "breast cancer cell lines", "cell lines erbb4", "lines erbb4 activation", "erbb4 activation enhances anchorage", "activation enhances anchorage independent", "enhances anchorage independent colony", "anchorage independent colony formation", "independent colony formation in", "colony formation in soft", "formation in soft agar", "in soft agar but", "soft agar but inhibits", "agar but inhibits cell", "but inhibits cell growth", "inhibits cell growth in", "cell growth in a", "growth in a monolayer", "in a monolayer culture.", "a monolayer culture. different", "monolayer culture. different erbb4", "culture. different erbb4 ligands", "different erbb4 ligands induce", "erbb4 ligands induce different", "ligands induce different gene", "induce different gene expression", "different gene expression changes", "gene expression changes in", "expression changes in breast", "changes in breast cancer", "in breast cancer cell", "breast cancer cell lines.", "cancer cell lines. some", "cell lines. some of", "lines. some of the", "some of the genes", "of the genes induced", "the genes induced in", "genes induced in response", "induced in response to", "in response to erbb4", "response to erbb4 signaling", "to erbb4 signaling in", "erbb4 signaling in breast", "signaling in breast cancer", "cancer cell lines are", "cell lines are rab2", "are rab2 eps15r", "rab2 eps15r and", "eps15r and gata4. it", "and gata4. it is", "gata4. it is not", "it is not known", "is not known if", "not known if these", "known if these gene", "if these gene are", "these gene are direct", "gene are direct transcriptional", "are direct transcriptional targets", "direct transcriptional targets of", "transcriptional targets of erbb4", "of erbb4 amin", "erbb4 amin et", "amin et al. 2004", "et al. 2004 .

transcriptome", "al. 2004 .

transcriptome and", "2004 .

transcriptome and chip", ".

transcriptome and chip seq", "and chip seq comparisons", "chip seq comparisons of", "seq comparisons of full", "comparisons of full length", "of full length and", "full length and intracellular", "length and intracellular domain", "and intracellular domain isoforms", "intracellular domain isoforms in", "domain isoforms in isogenic", "isoforms in isogenic mcf10a", "in isogenic mcf10a mammary", "isogenic mcf10a mammary cell", "mcf10a mammary cell background", "mammary cell background have", "cell background have revealed", "background have revealed the", "have revealed the diversification", "revealed the diversification of", "the diversification of erbb4", "diversification of erbb4 signaling", "of erbb4 signaling engendered", "erbb4 signaling engendered by", "signaling engendered by alternative", "engendered by alternative splicing", "by alternative splicing and", "alternative splicing and cleavage", "and cleavage wali", "cleavage wali et", "2014 . erbb4 broadly", ". erbb4 broadly affected", "erbb4 broadly affected protease", "broadly affected protease expression", "protease expression cholesterol", "expression cholesterol biosynthesis", "cholesterol biosynthesis hif1", "biosynthesis hif1 alpha", "alpha signaling and", "signaling and hippo", "and hippo signaling pathways", "signaling pathways and", "pathways and other", "and other pathways were", "other pathways were differentially", "pathways were differentially activated", "were differentially activated by", "differentially activated by cyt1", "activated by cyt1 and", "by cyt1 and cyt2", "cyt1 and cyt2 isoforms.", "and cyt2 isoforms. for", "cyt2 isoforms. for example", "for example cyt1", "example cyt1 promoted", "cyt1 promoted expression of", "promoted expression of transcription", "expression of transcription factors", "of transcription factors twist1", "transcription factors twist1 and", "factors twist1 and snail1", "twist1 and snail1 that", "and snail1 that promote", "snail1 that promote epithelial", "that promote epithelial mesenchymal", "promote epithelial mesenchymal transition.", "epithelial mesenchymal transition. hif1", "mesenchymal transition. hif1 alpha", "transition. hif1 alpha and", "hif1 alpha and hippo", "alpha and hippo signaling", "and hippo signaling are", "hippo signaling are mediated", "are mediated respectively", "respectively by binding", "by binding of erbb4", "binding of erbb4 to", "of erbb4 to hif1", "erbb4 to hif1 alpha", "to hif1 alpha and", "hif1 alpha and to", "alpha and to yap", "to yap paatero", "yap paatero et", "2012 komuro et", "2003 . erbb4 increases", ". erbb4 increases activity", "erbb4 increases activity of", "increases activity of the", "activity of the transcription", "of the transcription factor", "the transcription factor srebf2", "factor srebf2 resulting", "srebf2 resulting in", "resulting in increased expression", "in increased expression of", "increased expression of srebf2", "expression of srebf2 target", "of srebf2 target genes", "srebf2 target genes involved", "target genes involved in", "genes involved in cholesterol", "involved in cholesterol biosynthesis.", "in cholesterol biosynthesis. the", "cholesterol biosynthesis. the mechanism", "biosynthesis. the mechanism is", "the mechanism is not", "mechanism is not known", "is not known and", "not known and may", "known and may involve", "and may involve facilitation", "may involve facilitation of", "involve facilitation of srebf2", "facilitation of srebf2 cleavage", "of srebf2 cleavage through", "srebf2 cleavage through erbb4", "cleavage through erbb4 mediated", "through erbb4 mediated pi3k", "erbb4 mediated pi3k signaling", "pi3k signaling haskins", "signaling haskins et", "haskins et al. 2016", "et al. 2016 .

in", "al. 2016 .

in some", "2016 .

in some contexts", "some contexts erbb4", "contexts erbb4 promotes", "erbb4 promotes growth suppression", "promotes growth suppression or", "growth suppression or apoptosis", "or apoptosis penington", "apoptosis penington et", "et al. 2002", "al. 2002 .", "2002 . activation of", ". activation of erbb4", "activation of erbb4 in", "of erbb4 in breast", "erbb4 in breast cancer", "cancer cell lines leads", "cell lines leads to", "lines leads to jnk", "leads to jnk dependent", "to jnk dependent increase", "jnk dependent increase in", "dependent increase in brca1", "increase in brca1 mrna", "in brca1 mrna level", "brca1 mrna level and", "mrna level and mitotic", "level and mitotic cell", "and mitotic cell cycle", "mitotic cell cycle delay", "cycle delay but", "delay but the", "but the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been elucidated", "been elucidated muraoka", "elucidated muraoka cook", "cook et al. 2006", "al. 2006 . the", "2006 . the nature", ". the nature of", "the nature of growth", "nature of growth responses", "of growth responses may", "growth responses may be", "responses may be connected", "may be connected with", "be connected with the", "connected with the spliced", "with the spliced isoforms", "the spliced isoforms expressed.", "spliced isoforms expressed. in", "isoforms expressed. in comparisons", "expressed. in comparisons of", "in comparisons of cyt1", "comparisons of cyt1 vs", "of cyt1 vs cyt2", "vs cyt2 full", "cyt2 full length", "full length and icd", "and icd expression", "icd expression in", "expression in mammary cells", "mammary cells cyt1", "cells cyt1 was", "cyt1 was a weaker", "was a weaker growth", "a weaker growth inducer", "growth inducer associated", "inducer associated with", "associated with attenuated mapk", "with attenuated mapk signaling", "attenuated mapk signaling relative", "mapk signaling relative to", "signaling relative to cyt2", "to cyt2 wali", "cyt2 wali et", "2014 . erbb4 s80", "erbb4 s80 is also", "s80 is also able", "also able to translocate", "translocate to the mitochondrial", "to the mitochondrial matrix", "mitochondrial matrix presumably", "matrix presumably when", "presumably when its nuclear", "when its nuclear translocation", "its nuclear translocation is", "nuclear translocation is inhibited.", "translocation is inhibited. once", "is inhibited. once in", "inhibited. once in the", "once in the mitochondrion", "the mitochondrion the", "mitochondrion the bh3", "the bh3 domain of", "bh3 domain of erbb4", "of erbb4 characteristic", "erbb4 characteristic of", "characteristic of bcl2 family", "of bcl2 family members", "family members may", "members may enable", "may enable it to", "enable it to act", "it to act as", "to act as a", "act as a pro", "as a pro apoptotic", "a pro apoptotic factor", "apoptotic factor naresh", "factor naresh et", "naresh et al. 2006", "et al. 2006 .

erbb4", "al. 2006 .

erbb4 plays", "2006 .

erbb4 plays important", ".

erbb4 plays important roles", "plays important roles in", "important roles in the", "roles in the developing", "in the developing and", "the developing and adult", "developing and adult nervous", "and adult nervous system.", "adult nervous system. erbb4", "nervous system. erbb4 deficiency", "system. erbb4 deficiency in", "erbb4 deficiency in somatostatin", "deficiency in somatostatin expressing", "in somatostatin expressing neurons", "somatostatin expressing neurons of", "expressing neurons of the", "neurons of the thalamic", "of the thalamic reticular", "the thalamic reticular nucleus", "thalamic reticular nucleus alters", "reticular nucleus alters behaviors", "nucleus alters behaviors dependent", "alters behaviors dependent on", "behaviors dependent on sensory", "dependent on sensory selection", "sensory selection ahrens", "selection ahrens et", "ahrens et al. 2015", "et al. 2015 .", "al. 2015 . nrg1", "2015 . nrg1 activated", ". nrg1 activated erbb4", "nrg1 activated erbb4 signaling", "activated erbb4 signaling enhances", "erbb4 signaling enhances ampa", "signaling enhances ampa receptor", "enhances ampa receptor responses", "ampa receptor responses through", "receptor responses through pkc", "responses through pkc dependent", "through pkc dependent ampa", "pkc dependent ampa receptor", "dependent ampa receptor exocytosis.", "ampa receptor exocytosis. this", "receptor exocytosis. this results", "exocytosis. this results in", "this results in an", "results in an increased", "in an increased excitatory", "an increased excitatory input", "increased excitatory input to", "excitatory input to parvalbumin", "input to parvalbumin expressing", "to parvalbumin expressing inhibitory", "parvalbumin expressing inhibitory neurons", "expressing inhibitory neurons in", "inhibitory neurons in the", "neurons in the visual", "in the visual cortex", "the visual cortex and", "visual cortex and regulates", "cortex and regulates visual", "and regulates visual cortical", "regulates visual cortical plasticity", "cortical plasticity sun", "plasticity sun et", "sun et al. 2016", "et al. 2016 .", "al. 2016 . nrg1", "2016 . nrg1 activated", "activated erbb4 signaling is", "erbb4 signaling is involved", "signaling is involved in", "is involved in gabaergic", "involved in gabaergic activity", "in gabaergic activity in", "gabaergic activity in amygdala", "activity in amygdala which", "in amygdala which mediates", "amygdala which mediates fear", "which mediates fear conditioning", "fear conditioning fear", "conditioning fear memory", "memory lu", "lu et al. 2014", "et al. 2014 .", "al. 2014 . conditional", "2014 . conditional erbb4", ". conditional erbb4 deletion", "conditional erbb4 deletion from", "erbb4 deletion from fast", "deletion from fast spiking", "from fast spiking interneurons", "spiking interneurons chandelier", "interneurons chandelier and", "chandelier and basket cells", "and basket cells of", "basket cells of the", "cells of the cerebral", "of the cerebral cortex", "the cerebral cortex leads", "cerebral cortex leads to", "cortex leads to synaptic", "leads to synaptic defects", "to synaptic defects associated", "synaptic defects associated with", "defects associated with increased", "associated with increased locomotor", "with increased locomotor activity", "increased locomotor activity and", "locomotor activity and abnormal", "activity and abnormal emotional", "abnormal emotional social", "emotional social and", "social and cognitive function", "and cognitive function that", "cognitive function that can", "function that can be", "that can be linked", "can be linked to", "be linked to some", "linked to some of", "to some of the", "some of the schizophrenia", "of the schizophrenia features.", "the schizophrenia features. the", "schizophrenia features. the level", "features. the level of", "the level of gad1", "of gad1 gad67", "gad67 protein is", "protein is reduced in", "is reduced in the", "reduced in the cortex", "in the cortex of", "the cortex of conditional", "cortex of conditional erbb4", "of conditional erbb4 mutants.", "conditional erbb4 mutants. gad1", "erbb4 mutants. gad1 is", "mutants. gad1 is a", "gad1 is a gaba", "is a gaba synthesizing", "a gaba synthesizing enzyme.", "gaba synthesizing enzyme. cortical", "synthesizing enzyme. cortical mrna", "enzyme. cortical mrna levels", "cortical mrna levels of", "mrna levels of gad67", "levels of gad67 are", "of gad67 are consistently", "gad67 are consistently decreased", "are consistently decreased in", "consistently decreased in schizophrenia", "in schizophrenia del", "schizophrenia del pino", "del pino et al.", "pino et al. 2014", "al. 2014 . erbb4", "2014 . erbb4 is", ". erbb4 is expressed", "erbb4 is expressed in", "is expressed in the", "expressed in the gabaergic", "in the gabaergic neurons", "the gabaergic neurons of", "gabaergic neurons of the", "neurons of the bed", "of the bed nucleus", "the bed nucleus stria", "bed nucleus stria terminalis", "stria terminalis a", "terminalis a part", "a part of the", "part of the extended", "of the extended amygdala.", "the extended amygdala. inhibition", "extended amygdala. inhibition of", "amygdala. inhibition of nrg1", "inhibition of nrg1 triggered", "of nrg1 triggered erbb4", "nrg1 triggered erbb4 signaling", "triggered erbb4 signaling induces", "erbb4 signaling induces anxiety", "signaling induces anxiety like", "induces anxiety like behavior", "like behavior which", "behavior which depends", "which depends on gabaergic", "depends on gabaergic neurotransmission.", "on gabaergic neurotransmission. nrg1", "gabaergic neurotransmission. nrg1 erbb4", "neurotransmission. nrg1 erbb4 signaling", "nrg1 erbb4 signaling stimulates", "erbb4 signaling stimulates presynaptic", "signaling stimulates presynaptic gaba", "stimulates presynaptic gaba release", "gaba release but", "release but the", "the exact mechanism is", "exact mechanism is not", "not known geng", "known geng et", "geng et al. 2016", "2016 . nrg1 protects", ". nrg1 protects cortical", "nrg1 protects cortical interneurons", "protects cortical interneurons against", "cortical interneurons against ischemic", "interneurons against ischemic brain", "against ischemic brain injury", "ischemic brain injury through", "brain injury through erbb4", "injury through erbb4 mediated", "through erbb4 mediated increase", "erbb4 mediated increase in", "mediated increase in gabaergic", "increase in gabaergic transmission", "gabaergic transmission guan", "transmission guan et", "guan et al. 2015", "al. 2015 . nrg2", "2015 . nrg2 activated", ". nrg2 activated erbb4", "nrg2 activated erbb4 can", "activated erbb4 can reduce", "erbb4 can reduce the", "can reduce the duration", "reduce the duration of", "the duration of gabaergic", "duration of gabaergic transmission", "of gabaergic transmission by", "gabaergic transmission by binding", "transmission by binding to", "by binding to gaba", "binding to gaba receptors", "to gaba receptors at", "gaba receptors at the", "receptors at the postsynaptic", "at the postsynaptic membrane", "the postsynaptic membrane via", "postsynaptic membrane via their", "membrane via their gabra1", "via their gabra1 subunit", "their gabra1 subunit and", "gabra1 subunit and promoting", "subunit and promoting endocytosis", "and promoting endocytosis of", "promoting endocytosis of gaba", "endocytosis of gaba receptors", "gaba receptors mitchell", "receptors mitchell et", "mitchell et al. 2013", "et al. 2013 .", "al. 2013 . nrg1", "2013 . nrg1 promotes", ". nrg1 promotes synchronization", "nrg1 promotes synchronization of", "promotes synchronization of prefrontal", "synchronization of prefrontal cortex", "of prefrontal cortex interneurons", "prefrontal cortex interneurons in", "cortex interneurons in an", "interneurons in an erbb4", "in an erbb4 dependent", "an erbb4 dependent manner", "dependent manner hou", "manner hou et", "hou et al. 2014", "al. 2014 . nrg1", "2014 . nrg1 erbb4", ". nrg1 erbb4 signaling", "nrg1 erbb4 signaling protects", "erbb4 signaling protects neurons", "signaling protects neurons from", "protects neurons from the", "neurons from the cell", "from the cell death", "the cell death induced", "cell death induced by", "death induced by a", "induced by a mutant", "by a mutant form", "a mutant form of", "mutant form of the", "form of the amyloid", "of the amyloid precursor", "the amyloid precursor protein", "precursor protein app", "app woo", "woo et al. 2012", "et al. 2012 .

clinical", "al. 2012 .

clinical relevance", "2012 .

clinical relevance of", ".

clinical relevance of erbb4", "relevance of erbb4 has", "of erbb4 has been", "erbb4 has been identified", "has been identified in", "been identified in several", "identified in several contexts.", "in several contexts. in", "several contexts. in cancer", "in cancer putative", "cancer putative and", "putative and validated gain", "and validated gain of", "validated gain of function", "gain of function mutations", "of function mutations or", "function mutations or gene", "mutations or gene amplification", "or gene amplification that", "gene amplification that may", "amplification that may be", "that may be drivers", "may be drivers have", "be drivers have been", "drivers have been identified", "have been identified at", "been identified at modest", "identified at modest frequencies", "modest frequencies and", "frequencies and may", "and may also contribute", "may also contribute to", "also contribute to resistance", "contribute to resistance to", "to resistance to egfr", "resistance to egfr and", "to egfr and erbb2", "egfr and erbb2 targeted", "and erbb2 targeted therapies.", "erbb2 targeted therapies. this", "targeted therapies. this is", "therapies. this is noteworthy", "this is noteworthy as", "is noteworthy as erbb4", "noteworthy as erbb4 kinase", "as erbb4 kinase activity", "erbb4 kinase activity is", "kinase activity is inhibited", "activity is inhibited by", "is inhibited by pan", "inhibited by pan erbb", "by pan erbb tyrosine", "pan erbb tyrosine kinase", "erbb tyrosine kinase inhibitors", "kinase inhibitors including", "inhibitors including lapatinib", "including lapatinib which", "lapatinib which is", "which is approved by", "is approved by the", "approved by the us", "by the us fda.", "the us fda. the", "us fda. the reduced", "fda. the reduced prevalence", "the reduced prevalence relative", "reduced prevalence relative to", "prevalence relative to egfr", "relative to egfr and", "egfr and erbb2 in", "and erbb2 in cancer", "erbb2 in cancer may", "in cancer may reflect", "cancer may reflect more", "may reflect more restricted", "reflect more restricted expression", "more restricted expression of", "restricted expression of erbb4", "of erbb4 or", "erbb4 or differential", "differential signaling as", "signaling as specific", "as specific erbb4 isoforms", "specific erbb4 isoforms have", "erbb4 isoforms have been", "isoforms have been linked", "have been linked to", "been linked to growth", "linked to growth inhibition", "to growth inhibition or", "growth inhibition or apoptosis", "inhibition or apoptosis in", "or apoptosis in experimental", "apoptosis in experimental systems.", "in experimental systems. erbb2/erbb4", "experimental systems. erbb2/erbb4 heterodimers", "systems. erbb2/erbb4 heterodimers protect", "erbb2/erbb4 heterodimers protect cardiomyocytes", "protect cardiomyocytes so", "cardiomyocytes so reduced", "so reduced activity of", "reduced activity of erbb4", "activity of erbb4 in", "of erbb4 in patients", "erbb4 in patients treated", "in patients treated with", "patients treated with the", "treated with the erbb2", "with the erbb2 targeted", "the erbb2 targeted therapeutic", "erbb2 targeted therapeutic antibody", "targeted therapeutic antibody trastuzumab", "therapeutic antibody trastuzumab may", "antibody trastuzumab may contribute", "trastuzumab may contribute to", "may contribute to the", "contribute to the cardiotoxicity", "to the cardiotoxicity of", "the cardiotoxicity of this", "cardiotoxicity of this agent", "of this agent when", "this agent when used", "agent when used in", "when used in combination", "used in combination with", "combination with cardiotoxic", "cardiotoxic anthracyclines.

with the", "anthracyclines.

with the importance of", "the importance of erbb4", "importance of erbb4 in", "of erbb4 in developing", "erbb4 in developing and", "in developing and adult", "and adult nervous system", "nervous system nrg1", "system nrg1 and/or", "nrg1 and/or erbb4 polymorphisms", "erbb4 polymorphisms splicing", "polymorphisms splicing aberrations", "splicing aberrations and mutations", "aberrations and mutations have", "and mutations have been", "mutations have been linked", "been linked to nervous", "linked to nervous system", "to nervous system disorders", "nervous system disorders including", "system disorders including schizophrenia", "disorders including schizophrenia and", "including schizophrenia and amyotrophic", "schizophrenia and amyotrophic lateral", "and amyotrophic lateral sclerosis", "lateral sclerosis although", "sclerosis although these", "although these findings are", "these findings are not", "findings are not yet", "are not yet definitive.", "erbb4 also known as", "known as her4 belongs", "as her4 belongs to", "her4 belongs to the", "belongs to the erbb family", "to the erbb family of", "the erbb family of receptors", "family of receptors which", "of receptors which also", "receptors which also includes", "also includes erbb1 egfr/her1", "erbb2 her2/neu and", "and erbb3 her3 .", "erbb3 her3 . similar", "her3 . similar to egfr", "similar to egfr erbb4", "to egfr erbb4 has", "egfr erbb4 has an", "erbb4 has an extracellular ligand", "has an extracellular ligand binding", "an extracellular ligand binding domain", "ligand binding domain a", "binding domain a single", "domain a single transmembrane", "a single transmembrane domain and", "single transmembrane domain and a", "transmembrane domain and a cytoplasmic", "domain and a cytoplasmic domain", "and a cytoplasmic domain which", "a cytoplasmic domain which contains", "cytoplasmic domain which contains an", "domain which contains an active", "which contains an active tyrosine", "contains an active tyrosine kinase", "an active tyrosine kinase and", "active tyrosine kinase and a", "tyrosine kinase and a c", "kinase and a c tail", "and a c tail with", "a c tail with multiple", "c tail with multiple phosphorylation", "tail with multiple phosphorylation sites.", "with multiple phosphorylation sites. at", "multiple phosphorylation sites. at least", "phosphorylation sites. at least three", "sites. at least three and", "at least three and possibly", "least three and possibly four", "three and possibly four splicing", "and possibly four splicing isoforms", "possibly four splicing isoforms of", "four splicing isoforms of erbb4", "splicing isoforms of erbb4 exist", "isoforms of erbb4 exist that", "of erbb4 exist that differ", "erbb4 exist that differ in", "exist that differ in their", "that differ in their c", "differ in their c tail", "in their c tail and/or", "their c tail and/or the", "c tail and/or the extracellular", "tail and/or the extracellular juxtamembrane", "and/or the extracellular juxtamembrane regions:", "the extracellular juxtamembrane regions: erbb4", "extracellular juxtamembrane regions: erbb4 jm", "juxtamembrane regions: erbb4 jm a", "regions: erbb4 jm a cyt1", "jm a cyt1 erbb4", "a cyt1 erbb4 jm", "cyt1 erbb4 jm a", "erbb4 jm a cyt2 and", "jm a cyt2 and erbb4", "a cyt2 and erbb4 jm", "cyt2 and erbb4 jm b", "and erbb4 jm b cyt1", "jm b cyt1 the", "b cyt1 the existence", "cyt1 the existence of", "the existence of erbb4 jm", "existence of erbb4 jm b", "of erbb4 jm b cyt2", "erbb4 jm b cyt2 has", "jm b cyt2 has not", "b cyt2 has not been", "cyt2 has not been confirmed", "has not been confirmed .", "not been confirmed .

erbb4", "been confirmed .

erbb4 becomes", "confirmed .

erbb4 becomes activated", ".

erbb4 becomes activated by", "

erbb4 becomes activated by binding", "becomes activated by binding one", "activated by binding one of", "by binding one of its", "binding one of its seven", "one of its seven ligands", "its seven ligands three", "seven ligands three of", "ligands three of which", "three of which hb", "of which hb egf", "hb egf epiregulin epr", "egf epiregulin epr and", "epiregulin epr and betacellulin btc", "and betacellulin btc are", "betacellulin btc are egf", "btc are egf like", "are egf like elenius", "egf like elenius et", "like elenius et al.", "et al. 1997 riese", "al. 1997 riese et", "1997 riese et al.", "al. 1998 while", "1998 while four", "four nrg1 nrg2", "nrg1 nrg2 nrg3", "nrg2 nrg3 and nrg4", "nrg3 and nrg4 belong", "and nrg4 belong to", "nrg4 belong to the", "belong to the related neuregulin", "to the related neuregulin family", "related neuregulin family tzahar", "neuregulin family tzahar et", "family tzahar et al.", "et al. 1994 carraway", "al. 1994 carraway et", "1994 carraway et al.", "et al. 1997 zhang", "al. 1997 zhang et", "1997 zhang et al.", "et al. 1997 hayes", "al. 1997 hayes et", "1997 hayes et al.", "hayes et al. 2007 .", "et al. 2007 . upon", "al. 2007 . upon ligand", "2007 . upon ligand binding", "upon ligand binding erbb4", "ligand binding erbb4 forms", "binding erbb4 forms homodimers", "erbb4 forms homodimers sweeney", "forms homodimers sweeney et", "homodimers sweeney et al.", "et al. 2000 or", "al. 2000 or it", "2000 or it heterodimerizes", "or it heterodimerizes with erbb2", "heterodimerizes with erbb2 li", "with erbb2 li et", "erbb2 li et al.", "li et al. 2007 .", "et al. 2007 . dimers", "al. 2007 . dimers of", "2007 . dimers of erbb4", ". dimers of erbb4 undergo", "dimers of erbb4 undergo trans", "of erbb4 undergo trans autophosphorylation", "erbb4 undergo trans autophosphorylation on", "undergo trans autophosphorylation on tyrosine", "trans autophosphorylation on tyrosine residues", "autophosphorylation on tyrosine residues in", "on tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "the c tail cohen", "c tail cohen et", "tail cohen et al.", "et al. 1996 kaushansky", "al. 1996 kaushansky et", "1996 kaushansky et al.", "et al. 2008 hazan", "al. 2008 hazan et", "2008 hazan et al.", "et al. 1990 li", "al. 1990 li et", "1990 li et al.", "al. 2007 triggering", "2007 triggering downstream", "triggering downstream signaling cascades. the", "downstream signaling cascades. the pathway", "signaling cascades. the pathway signaling", "cascades. the pathway signaling by", "the pathway signaling by erbb4", "pathway signaling by erbb4 only", "signaling by erbb4 only shows", "by erbb4 only shows signaling", "erbb4 only shows signaling by", "only shows signaling by erbb4", "shows signaling by erbb4 homodimers.", "signaling by erbb4 homodimers. signaling", "by erbb4 homodimers. signaling by", "erbb4 homodimers. signaling by heterodimers", "homodimers. signaling by heterodimers of", "signaling by heterodimers of erbb4", "by heterodimers of erbb4 and", "heterodimers of erbb4 and erbb2", "of erbb4 and erbb2 is", "erbb4 and erbb2 is shown", "and erbb2 is shown in", "erbb2 is shown in the", "is shown in the pathway", "shown in the pathway signaling", "in the pathway signaling by", "the pathway signaling by erbb2.", "pathway signaling by erbb2. ligand", "signaling by erbb2. ligand stimulated", "by erbb2. ligand stimulated erbb4", "erbb2. ligand stimulated erbb4 is", "ligand stimulated erbb4 is also", "stimulated erbb4 is also able", "erbb4 is also able to", "is also able to form", "also able to form heterodimers", "able to form heterodimers with", "to form heterodimers with ligand", "form heterodimers with ligand stimulated", "heterodimers with ligand stimulated egfr", "ligand stimulated egfr cohen", "stimulated egfr cohen et", "egfr cohen et al.", "et al. 1996 and", "al. 1996 and ligand", "1996 and ligand stimulated", "ligand stimulated erbb3 riese", "stimulated erbb3 riese et", "erbb3 riese et al.", "riese et al. 1995 .", "et al. 1995 . dimers", "al. 1995 . dimers of", "1995 . dimers of erbb4", ". dimers of erbb4 with", "dimers of erbb4 with egfr", "of erbb4 with egfr and", "erbb4 with egfr and dimers", "with egfr and dimers of", "egfr and dimers of erbb4", "and dimers of erbb4 with", "dimers of erbb4 with erbb3", "of erbb4 with erbb3 were", "erbb4 with erbb3 were demonstrated", "with erbb3 were demonstrated in", "erbb3 were demonstrated in mouse", "were demonstrated in mouse cell", "demonstrated in mouse cell lines", "in mouse cell lines in", "mouse cell lines in which", "cell lines in which human", "lines in which human erbb4", "in which human erbb4 and", "which human erbb4 and egfr", "human erbb4 and egfr or", "erbb4 and egfr or erbb3", "and egfr or erbb3 were", "egfr or erbb3 were exogenously", "or erbb3 were exogenously expressed.", "erbb3 were exogenously expressed. these", "were exogenously expressed. these heterodimers", "exogenously expressed. these heterodimers undergo", "expressed. these heterodimers undergo trans", "these heterodimers undergo trans autophosphorylation.", "heterodimers undergo trans autophosphorylation. the", "undergo trans autophosphorylation. the promiscuous", "trans autophosphorylation. the promiscuous heteromerization", "autophosphorylation. the promiscuous heteromerization of", "the promiscuous heteromerization of erbbs", "promiscuous heteromerization of erbbs adds", "heteromerization of erbbs adds combinatorial", "of erbbs adds combinatorial diversity", "erbbs adds combinatorial diversity to", "adds combinatorial diversity to erbb", "combinatorial diversity to erbb signaling", "diversity to erbb signaling processes.", "to erbb signaling processes. as", "erbb signaling processes. as erbb4", "signaling processes. as erbb4 binds", "processes. as erbb4 binds more", "as erbb4 binds more ligands", "erbb4 binds more ligands than", "binds more ligands than other", "more ligands than other erbbs", "than other erbbs but", "other erbbs but has", "erbbs but has restricted", "has restricted expression erbb4", "restricted expression erbb4 expression", "expression erbb4 expression channels", "erbb4 expression channels responses to", "expression channels responses to erbb", "channels responses to erbb ligands.", "responses to erbb ligands. the", "to erbb ligands. the signaling", "erbb ligands. the signaling capabilities", "ligands. the signaling capabilities of", "the signaling capabilities of the", "signaling capabilities of the four", "capabilities of the four receptors", "of the four receptors have", "the four receptors have been", "four receptors have been compared", "have been compared schulze", "been compared schulze et", "compared schulze et al.", "schulze et al. 2005 .

as", "et al. 2005 .

as for", "al. 2005 .

as for other", "2005 .

as for other receptor", ".

as for other receptor tyrosine", "for other receptor tyrosine kinases", "receptor tyrosine kinases erbb4", "tyrosine kinases erbb4 signaling", "kinases erbb4 signaling effectors", "erbb4 signaling effectors are largely", "signaling effectors are largely dictated", "effectors are largely dictated through", "are largely dictated through binding", "largely dictated through binding of", "dictated through binding of effector", "through binding of effector proteins", "binding of effector proteins to", "of effector proteins to erbb4", "effector proteins to erbb4 peptides", "proteins to erbb4 peptides that", "to erbb4 peptides that are", "erbb4 peptides that are phosphorylated", "peptides that are phosphorylated upon", "that are phosphorylated upon ligand", "are phosphorylated upon ligand binding.", "phosphorylated upon ligand binding. all", "upon ligand binding. all splicing", "ligand binding. all splicing isoforms", "binding. all splicing isoforms of", "all splicing isoforms of erbb4", "splicing isoforms of erbb4 possess", "isoforms of erbb4 possess two", "of erbb4 possess two tyrosine", "erbb4 possess two tyrosine residues", "possess two tyrosine residues in", "two tyrosine residues in the", "in the c tail that", "the c tail that serve", "c tail that serve as", "tail that serve as docking", "that serve as docking sites", "serve as docking sites for", "as docking sites for shc1", "sites for shc1 kaushansky", "for shc1 kaushansky et", "shc1 kaushansky et al.", "et al. 2008 pinkas", "al. 2008 pinkas kramarski", "2008 pinkas kramarski et", "pinkas kramarski et al. 1996", "et al. 1996 cohen", "al. 1996 cohen et", "1996 cohen et al.", "cohen et al. 1996 .", "et al. 1996 . once", "al. 1996 . once bound", "1996 . once bound to", ". once bound to erbb4", "bound to erbb4 shc1", "to erbb4 shc1 becomes", "erbb4 shc1 becomes phosphorylated", "shc1 becomes phosphorylated on tyrosine", "becomes phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues by", "on tyrosine residues by the", "tyrosine residues by the tyrosine", "residues by the tyrosine kinase", "by the tyrosine kinase activity", "the tyrosine kinase activity of", "tyrosine kinase activity of erbb4", "activity of erbb4 which", "of erbb4 which enables", "erbb4 which enables it", "which enables it to recruit", "enables it to recruit the", "it to recruit the complex", "to recruit the complex of", "recruit the complex of grb2", "the complex of grb2 and", "complex of grb2 and sos1", "grb2 and sos1 resulting", "and sos1 resulting in", "sos1 resulting in the", "resulting in the guanyl nucleotide", "in the guanyl nucleotide exchange", "the guanyl nucleotide exchange on", "guanyl nucleotide exchange on ras", "nucleotide exchange on ras and", "exchange on ras and activation", "on ras and activation of", "ras and activation of raf", "and activation of raf and", "activation of raf and map", "of raf and map kinase", "raf and map kinase cascade", "map kinase cascade kainulainen", "kinase cascade kainulainen et", "cascade kainulainen et al.", "kainulainen et al. 2000 .", "et al. 2000 .

the", "al. 2000 .

the cyt1", "2000 .

the cyt1 isoforms", ".

the cyt1 isoforms of", "

the cyt1 isoforms of erbb4", "cyt1 isoforms of erbb4 also", "isoforms of erbb4 also possess", "of erbb4 also possess a", "erbb4 also possess a c", "also possess a c tail", "possess a c tail tyrosine", "a c tail tyrosine residue", "c tail tyrosine residue that", "tyrosine residue that upon", "residue that upon trans", "that upon trans autophosphorylation", "upon trans autophosphorylation serves", "trans autophosphorylation serves as", "autophosphorylation serves as a", "serves as a docking site", "as a docking site for", "a docking site for the", "docking site for the p85", "site for the p85 alpha", "for the p85 alpha subunit", "the p85 alpha subunit of", "p85 alpha subunit of pi3k", "subunit of pi3k kaushansky", "of pi3k kaushansky et", "pi3k kaushansky et al.", "et al. 2008 cohen", "al. 2008 cohen et", "2008 cohen et al.", "al. 1996 leading", "1996 leading to", "leading to assembly of an", "to assembly of an active", "assembly of an active pi3k", "of an active pi3k complex", "an active pi3k complex that", "active pi3k complex that converts", "pi3k complex that converts pip2", "complex that converts pip2 to", "that converts pip2 to pip3", "converts pip2 to pip3 and", "pip2 to pip3 and activates", "to pip3 and activates akt", "pip3 and activates akt signaling", "activates akt signaling kainulainen", "akt signaling kainulainen et", "signaling kainulainen et al.", "et al. 2000 .

besides", "al. 2000 .

besides signaling", "2000 .

besides signaling as", ".

besides signaling as a", "

besides signaling as a conventional", "signaling as a conventional transmembrane", "as a conventional transmembrane receptor", "a conventional transmembrane receptor kinase", "transmembrane receptor kinase erbb4", "receptor kinase erbb4 differs", "kinase erbb4 differs from", "erbb4 differs from other erbbs", "differs from other erbbs in", "from other erbbs in that", "other erbbs in that jm", "erbbs in that jm a", "in that jm a isoforms", "that jm a isoforms signal", "jm a isoforms signal through", "a isoforms signal through efficient", "isoforms signal through efficient release", "signal through efficient release of", "through efficient release of a", "efficient release of a soluble", "release of a soluble intracellular", "of a soluble intracellular domain.", "a soluble intracellular domain. ligand", "soluble intracellular domain. ligand activated", "intracellular domain. ligand activated homodimers", "domain. ligand activated homodimers of", "ligand activated homodimers of erbb4", "activated homodimers of erbb4 jm", "homodimers of erbb4 jm a", "of erbb4 jm a isoforms", "jm a isoforms erbb4", "a isoforms erbb4 jm", "isoforms erbb4 jm a", "erbb4 jm a cyt1 and", "jm a cyt1 and erbb4", "a cyt1 and erbb4 jm", "cyt1 and erbb4 jm a", "and erbb4 jm a cyt2", "jm a cyt2 undergo", "a cyt2 undergo proteolytic", "cyt2 undergo proteolytic cleavage", "undergo proteolytic cleavage by adam17", "cleavage by adam17 tace", "adam17 tace in", "tace in the juxtamembrane", "the juxtamembrane region resulting", "juxtamembrane region resulting in", "region resulting in shedding", "resulting in shedding of the", "in shedding of the extracellular", "shedding of the extracellular domain", "of the extracellular domain and", "the extracellular domain and formation", "extracellular domain and formation of", "domain and formation of an", "and formation of an 80", "formation of an 80 kda", "of an 80 kda membrane", "an 80 kda membrane bound", "80 kda membrane bound erbb4", "kda membrane bound erbb4 fragment", "membrane bound erbb4 fragment known", "bound erbb4 fragment known as", "erbb4 fragment known as erbb4", "fragment known as erbb4 m80", "as erbb4 m80 rio", "erbb4 m80 rio et", "m80 rio et al.", "et al. 2000 cheng", "al. 2000 cheng et", "2000 cheng et al.", "cheng et al. 2003 .", "et al. 2003 . erbb4", "al. 2003 . erbb4 m80", "2003 . erbb4 m80 undergoes", ". erbb4 m80 undergoes further", "erbb4 m80 undergoes further proteolytic", "m80 undergoes further proteolytic cleavage", "further proteolytic cleavage mediated", "proteolytic cleavage mediated by", "cleavage mediated by the", "mediated by the gamma secretase", "by the gamma secretase complex", "gamma secretase complex which", "secretase complex which releases", "complex which releases the", "which releases the soluble 80", "releases the soluble 80 kda", "the soluble 80 kda erbb4", "soluble 80 kda erbb4 intracellular", "80 kda erbb4 intracellular domain", "erbb4 intracellular domain known", "intracellular domain known as", "domain known as erbb4", "known as erbb4 s80 or", "as erbb4 s80 or e4icd", "s80 or e4icd into", "or e4icd into the", "e4icd into the cytosol", "into the cytosol ni", "the cytosol ni et", "cytosol ni et al.", "ni et al. 2001 .", "et al. 2001 . erbb4", "al. 2001 . erbb4 s80", "2001 . erbb4 s80 is", ". erbb4 s80 is able", "erbb4 s80 is able to", "s80 is able to translocate", "is able to translocate to", "able to translocate to the", "to translocate to the nucleus", "to the nucleus promote", "the nucleus promote nuclear", "nucleus promote nuclear translocation", "promote nuclear translocation of various", "nuclear translocation of various transcription", "translocation of various transcription factors", "various transcription factors and", "transcription factors and act", "factors and act as", "and act as a transcription", "act as a transcription co", "as a transcription co factor.", "a transcription co factor. for", "transcription co factor. for example", "factor. for example in", "for example in mammary", "example in mammary cells", "in mammary cells erbb4", "mammary cells erbb4 binds", "cells erbb4 binds sh2", "erbb4 binds sh2 transcription factor", "binds sh2 transcription factor stat5a.", "sh2 transcription factor stat5a. erbb4", "transcription factor stat5a. erbb4 s80", "factor stat5a. erbb4 s80 shuttles", "stat5a. erbb4 s80 shuttles stat5a", "erbb4 s80 shuttles stat5a to", "s80 shuttles stat5a to the", "shuttles stat5a to the nucleus", "to the nucleus and", "the nucleus and actsa", "nucleus and actsa as", "and actsa as a stat5a", "actsa as a stat5a co", "as a stat5a co factor", "a stat5a co factor in", "stat5a co factor in binding", "co factor in binding to", "factor in binding to and", "in binding to and promoting", "binding to and promoting transcription", "to and promoting transcription from", "and promoting transcription from the", "promoting transcription from the beta", "transcription from the beta casein", "the beta casein csn2", "casein csn2 promoter", "csn2 promoter and", "promoter and may be", "and may be involved in", "may be involved in the", "be involved in the regulation", "involved in the regulation of", "in the regulation of other", "the regulation of other lactation", "regulation of other lactation related", "of other lactation related genes", "lactation related genes jones", "related genes jones et", "genes jones et al.", "et al. 1999 williams", "al. 1999 williams et", "1999 williams et al.", "et al. 2004 muraoka", "al. 2004 muraoka cook", "2004 muraoka cook et", "muraoka cook et al. 2008", "cook et al. 2008 .", "et al. 2008 . erbb4", "al. 2008 . erbb4 s80", "2008 . erbb4 s80 binds", ". erbb4 s80 binds activated", "erbb4 s80 binds activated estrogen", "s80 binds activated estrogen receptor", "binds activated estrogen receptor in", "activated estrogen receptor in the", "estrogen receptor in the nucleus", "receptor in the nucleus and", "in the nucleus and acts", "the nucleus and acts as", "nucleus and acts as a", "and acts as a transcriptional", "acts as a transcriptional co", "as a transcriptional co factor", "a transcriptional co factor in", "transcriptional co factor in promoting", "co factor in promoting transcription", "factor in promoting transcription of", "in promoting transcription of some", "promoting transcription of some estrogen", "transcription of some estrogen regulated", "of some estrogen regulated genes", "estrogen regulated genes including", "regulated genes including progesterone", "genes including progesterone receptor", "including progesterone receptor gene nr3c3", "progesterone receptor gene nr3c3 and", "receptor gene nr3c3 and cxcl12", "nr3c3 and cxcl12 sdf1", "sdf1 zhu et", "zhu et al. 2006 .", "et al. 2006 . in", "al. 2006 . in neuronal", "2006 . in neuronal precursors", "in neuronal precursors erbb4", "neuronal precursors erbb4 s80", "precursors erbb4 s80 binds", "erbb4 s80 binds the complex", "s80 binds the complex of", "binds the complex of tab", "the complex of tab and", "complex of tab and ncor1", "tab and ncor1 helps", "and ncor1 helps to", "ncor1 helps to move", "helps to move the complex", "to move the complex into", "move the complex into the", "the complex into the nucleus", "into the nucleus and", "the nucleus and is", "nucleus and is a", "and is a co factor", "is a co factor of", "a co factor of tab:ncor1", "co factor of tab:ncor1 mediated", "factor of tab:ncor1 mediated inhibition", "of tab:ncor1 mediated inhibition of", "tab:ncor1 mediated inhibition of expression", "mediated inhibition of expression of", "inhibition of expression of astrocyte", "of expression of astrocyte differentiation", "expression of astrocyte differentiation genes", "of astrocyte differentiation genes gfap", "astrocyte differentiation genes gfap and", "differentiation genes gfap and s100b", "gfap and s100b sardi", "and s100b sardi et", "s100b sardi et al.", "sardi et al. 2006 .

the", "et al. 2006 .

the c", "al. 2006 .

the c tail", "2006 .

the c tail of", ".

the c tail of erbb4", "c tail of erbb4 possesses", "tail of erbb4 possesses several", "of erbb4 possesses several ww", "erbb4 possesses several ww domain", "possesses several ww domain binding", "several ww domain binding motifs", "domain binding motifs three", "binding motifs three in", "motifs three in cyt1", "three in cyt1 isoform and", "in cyt1 isoform and two", "cyt1 isoform and two in", "isoform and two in cyt2", "and two in cyt2 isoform", "cyt2 isoform which", "isoform which enable", "which enable interaction of erbb4", "enable interaction of erbb4 with", "interaction of erbb4 with ww", "of erbb4 with ww domain", "erbb4 with ww domain containing", "with ww domain containing proteins.", "ww domain containing proteins. erbb4", "domain containing proteins. erbb4 s80", "proteins. erbb4 s80 through", "erbb4 s80 through ww", "s80 through ww domain", "through ww domain binding motifs", "domain binding motifs interacts", "binding motifs interacts with", "motifs interacts with yap1", "interacts with yap1 transcription factor", "yap1 transcription factor a", "transcription factor a known", "factor a known proto", "known proto oncogene and", "proto oncogene and is", "oncogene and is a", "and is a co regulator", "is a co regulator of", "a co regulator of yap1", "co regulator of yap1 mediated", "regulator of yap1 mediated transcription", "of yap1 mediated transcription in", "yap1 mediated transcription in association", "mediated transcription in association with", "transcription in association with tead", "in association with tead transcription", "association with tead transcription factors", "tead transcription factors komuro", "transcription factors komuro et", "factors komuro et al.", "et al. 2003 omerovic", "al. 2003 omerovic et", "2003 omerovic et al.", "omerovic et al. 2004 .", "et al. 2004 . hence", "2004 . hence the", ". hence the ww", "hence the ww binding", "the ww binding motif couples", "ww binding motif couples erbb4", "binding motif couples erbb4 to", "motif couples erbb4 to the", "couples erbb4 to the major", "erbb4 to the major effector", "to the major effector arm", "the major effector arm of", "major effector arm of the", "effector arm of the hippo", "arm of the hippo signaling", "of the hippo signaling pathway.", "the hippo signaling pathway. the", "hippo signaling pathway. the tumor", "signaling pathway. the tumor suppressor", "pathway. the tumor suppressor wwox", "tumor suppressor wwox another", "suppressor wwox another ww", "wwox another ww domain", "another ww domain containing protein", "domain containing protein competes", "containing protein competes with", "protein competes with yap1", "competes with yap1 in binding", "with yap1 in binding to", "yap1 in binding to erbb4", "in binding to erbb4 s80", "binding to erbb4 s80 and", "to erbb4 s80 and prevents", "erbb4 s80 and prevents translocation", "s80 and prevents translocation of", "and prevents translocation of erbb4", "prevents translocation of erbb4 s80", "translocation of erbb4 s80 to", "of erbb4 s80 to the", "erbb4 s80 to the nucleus", "to the nucleus aqeilan", "the nucleus aqeilan et", "nucleus aqeilan et al.", "aqeilan et al. 2005 .

ww", "et al. 2005 .

ww domain", "al. 2005 .

ww domain binding", "2005 .

ww domain binding motifs", ".

ww domain binding motifs in", "domain binding motifs in the", "binding motifs in the c", "motifs in the c tail", "in the c tail of", "the c tail of erbb4", "c tail of erbb4 play", "tail of erbb4 play an", "of erbb4 play an important", "erbb4 play an important role", "play an important role in", "an important role in the", "important role in the downregulation", "role in the downregulation of", "in the downregulation of erbb4", "the downregulation of erbb4 receptor", "downregulation of erbb4 receptor signaling", "erbb4 receptor signaling enabling", "receptor signaling enabling the", "signaling enabling the interaction", "enabling the interaction of intact", "the interaction of intact erbb4", "of intact erbb4 erbb4", "intact erbb4 erbb4 m80", "erbb4 erbb4 m80 and", "erbb4 m80 and erbb4 s80", "m80 and erbb4 s80 with", "and erbb4 s80 with nedd4", "erbb4 s80 with nedd4 family", "s80 with nedd4 family of", "with nedd4 family of e3", "nedd4 family of e3 ubiquitin", "family of e3 ubiquitin ligases", "of e3 ubiquitin ligases wwp1", "e3 ubiquitin ligases wwp1 and", "ubiquitin ligases wwp1 and itch.", "ligases wwp1 and itch. the", "wwp1 and itch. the interaction", "and itch. the interaction of", "itch. the interaction of wwp1", "the interaction of wwp1 and", "interaction of wwp1 and itch", "of wwp1 and itch with", "wwp1 and itch with intact", "and itch with intact erbb4", "itch with intact erbb4 is", "with intact erbb4 is independent", "intact erbb4 is independent of", "erbb4 is independent of receptor", "is independent of receptor activation", "independent of receptor activation and", "of receptor activation and autophosphorylation.", "receptor activation and autophosphorylation. binding", "activation and autophosphorylation. binding of", "and autophosphorylation. binding of wwp1", "autophosphorylation. binding of wwp1 and", "binding of wwp1 and itch", "of wwp1 and itch ubiquitin", "wwp1 and itch ubiquitin ligases", "and itch ubiquitin ligases leads", "itch ubiquitin ligases leads to", "ubiquitin ligases leads to ubiquitination", "ligases leads to ubiquitination of", "leads to ubiquitination of erbb4", "to ubiquitination of erbb4 and", "ubiquitination of erbb4 and its", "of erbb4 and its cleavage", "erbb4 and its cleavage products", "its cleavage products and", "cleavage products and subsequent", "products and subsequent degradation", "and subsequent degradation through both", "subsequent degradation through both proteasomal", "degradation through both proteasomal and", "through both proteasomal and lysosomal", "both proteasomal and lysosomal routes", "and lysosomal routes omerovic", "lysosomal routes omerovic et", "routes omerovic et al.", "et al. 2007 feng", "al. 2007 feng et", "2007 feng et al.", "feng et al. 2009 .", "et al. 2009 . in", "al. 2009 . in addition", ". in addition the", "in addition the s80", "addition the s80 cleavage", "the s80 cleavage product of", "s80 cleavage product of erbb4", "cleavage product of erbb4 jm", "product of erbb4 jm a", "of erbb4 jm a cyt", "erbb4 jm a cyt 1", "jm a cyt 1 isoform", "a cyt 1 isoform is", "cyt 1 isoform is the", "1 isoform is the target", "isoform is the target of", "is the target of nedd4", "the target of nedd4 ubiquitin", "target of nedd4 ubiquitin ligase.", "of nedd4 ubiquitin ligase. nedd4", "nedd4 ubiquitin ligase. nedd4 binds", "ubiquitin ligase. nedd4 binds erbb4", "ligase. nedd4 binds erbb4 jm", "nedd4 binds erbb4 jm a", "binds erbb4 jm a cyt", "jm a cyt 1 s80", "cyt 1 s80 erbb4jmacyt1s80", "s80 erbb4jmacyt1s80 through", "erbb4jmacyt1s80 through its pik3r1", "through its pik3r1 interaction site", "its pik3r1 interaction site and", "pik3r1 interaction site and mediates", "interaction site and mediates erbb4jmacyt1s80", "site and mediates erbb4jmacyt1s80 ubiquitination", "mediates erbb4jmacyt1s80 ubiquitination thereby", "erbb4jmacyt1s80 ubiquitination thereby decreasing", "ubiquitination thereby decreasing the", "thereby decreasing the amount of", "decreasing the amount of erbb4jmacyt1s80", "the amount of erbb4jmacyt1s80 that", "amount of erbb4jmacyt1s80 that reaches", "of erbb4jmacyt1s80 that reaches the", "erbb4jmacyt1s80 that reaches the nucleus", "reaches the nucleus zeng", "the nucleus zeng et", "nucleus zeng et al.", "zeng et al. 2009 .

erbb4", "et al. 2009 .

erbb4 also", "al. 2009 .

erbb4 also binds", "2009 .

erbb4 also binds the", ".

erbb4 also binds the e3", "also binds the e3 ubiquitin", "binds the e3 ubiquitin ligase", "the e3 ubiquitin ligase mdm2", "ubiquitin ligase mdm2 and", "ligase mdm2 and inhibitor", "mdm2 and inhibitor of", "inhibitor of p53 arasada", "of p53 arasada et", "p53 arasada et al.", "arasada et al. 2005 .", "et al. 2005 . other", "al. 2005 . other proteins", "2005 . other proteins that", ". other proteins that bind", "other proteins that bind to", "proteins that bind to erbb4", "that bind to erbb4 intracellular", "bind to erbb4 intracellular domain", "to erbb4 intracellular domain have", "erbb4 intracellular domain have been", "intracellular domain have been identified", "domain have been identified by", "have been identified by co", "been identified by co immunoprecipitation", "identified by co immunoprecipitation and", "by co immunoprecipitation and mass", "co immunoprecipitation and mass spectrometry", "and mass spectrometry gilmore", "mass spectrometry gilmore hebert", "spectrometry gilmore hebert et", "hebert et al. 2010", "2010 and include", "and include transcriptional co repressor", "include transcriptional co repressor trim28/kap1", "co repressor trim28/kap1 which", "repressor trim28/kap1 which promotes", "trim28/kap1 which promotes chromatin", "which promotes chromatin compaction. dna", "promotes chromatin compaction. dna damage", "chromatin compaction. dna damage signaling", "compaction. dna damage signaling through", "dna damage signaling through atm", "damage signaling through atm releases", "signaling through atm releases trim28", "through atm releases trim28 associated", "atm releases trim28 associated heterochromatinization.", "releases trim28 associated heterochromatinization. interactions", "trim28 associated heterochromatinization. interactions of", "associated heterochromatinization. interactions of erbb4", "heterochromatinization. interactions of erbb4 with", "interactions of erbb4 with trim28", "of erbb4 with trim28 and", "erbb4 with trim28 and mdm2", "with trim28 and mdm2 may", "trim28 and mdm2 may be", "and mdm2 may be important", "mdm2 may be important for", "may be important for integration", "be important for integration of", "important for integration of growth", "for integration of growth factor", "integration of growth factor responses", "of growth factor responses and", "growth factor responses and dna", "factor responses and dna damage", "responses and dna damage responses.

in", "and dna damage responses.

in human", "dna damage responses.

in human breast", "damage responses.

in human breast cancer", "responses.

in human breast cancer cell", "human breast cancer cell lines", "cancer cell lines erbb4", "cell lines erbb4 activation", "lines erbb4 activation enhances", "erbb4 activation enhances anchorage independent", "activation enhances anchorage independent colony", "enhances anchorage independent colony formation", "anchorage independent colony formation in", "independent colony formation in soft", "colony formation in soft agar", "formation in soft agar but", "in soft agar but inhibits", "soft agar but inhibits cell", "agar but inhibits cell growth", "but inhibits cell growth in", "inhibits cell growth in a", "cell growth in a monolayer", "growth in a monolayer culture.", "in a monolayer culture. different", "a monolayer culture. different erbb4", "monolayer culture. different erbb4 ligands", "culture. different erbb4 ligands induce", "different erbb4 ligands induce different", "erbb4 ligands induce different gene", "ligands induce different gene expression", "induce different gene expression changes", "different gene expression changes in", "gene expression changes in breast", "expression changes in breast cancer", "changes in breast cancer cell", "in breast cancer cell lines.", "breast cancer cell lines. some", "cancer cell lines. some of", "cell lines. some of the", "lines. some of the genes", "some of the genes induced", "of the genes induced in", "the genes induced in response", "genes induced in response to", "induced in response to erbb4", "in response to erbb4 signaling", "response to erbb4 signaling in", "to erbb4 signaling in breast", "erbb4 signaling in breast cancer", "signaling in breast cancer cell", "in breast cancer cell lines", "breast cancer cell lines are", "cancer cell lines are rab2", "lines are rab2 eps15r", "are rab2 eps15r and", "rab2 eps15r and gata4.", "eps15r and gata4. it is", "and gata4. it is not", "gata4. it is not known", "it is not known if", "is not known if these", "not known if these gene", "known if these gene are", "if these gene are direct", "these gene are direct transcriptional", "gene are direct transcriptional targets", "are direct transcriptional targets of", "direct transcriptional targets of erbb4", "targets of erbb4 amin", "of erbb4 amin et", "erbb4 amin et al.", "amin et al. 2004 .

transcriptome", "et al. 2004 .

transcriptome and", "al. 2004 .

transcriptome and chip", "2004 .

transcriptome and chip seq", ".

transcriptome and chip seq comparisons", "and chip seq comparisons of", "chip seq comparisons of full", "seq comparisons of full length", "comparisons of full length and", "of full length and intracellular", "full length and intracellular domain", "length and intracellular domain isoforms", "and intracellular domain isoforms in", "intracellular domain isoforms in isogenic", "domain isoforms in isogenic mcf10a", "isoforms in isogenic mcf10a mammary", "in isogenic mcf10a mammary cell", "isogenic mcf10a mammary cell background", "mcf10a mammary cell background have", "mammary cell background have revealed", "cell background have revealed the", "background have revealed the diversification", "have revealed the diversification of", "revealed the diversification of erbb4", "the diversification of erbb4 signaling", "diversification of erbb4 signaling engendered", "of erbb4 signaling engendered by", "erbb4 signaling engendered by alternative", "signaling engendered by alternative splicing", "engendered by alternative splicing and", "by alternative splicing and cleavage", "splicing and cleavage wali", "and cleavage wali et", "cleavage wali et al.", "wali et al. 2014", "2014 . erbb4 broadly affected", ". erbb4 broadly affected protease", "erbb4 broadly affected protease expression", "affected protease expression cholesterol", "protease expression cholesterol biosynthesis", "cholesterol biosynthesis hif1 alpha", "biosynthesis hif1 alpha signaling", "hif1 alpha signaling and", "alpha signaling and hippo", "signaling and hippo signaling", "hippo signaling pathways and", "signaling pathways and other", "pathways and other pathways", "and other pathways were differentially", "other pathways were differentially activated", "pathways were differentially activated by", "were differentially activated by cyt1", "differentially activated by cyt1 and", "activated by cyt1 and cyt2", "by cyt1 and cyt2 isoforms.", "cyt1 and cyt2 isoforms. for", "and cyt2 isoforms. for example", "isoforms. for example cyt1", "for example cyt1 promoted", "example cyt1 promoted expression", "cyt1 promoted expression of transcription", "promoted expression of transcription factors", "expression of transcription factors twist1", "of transcription factors twist1 and", "transcription factors twist1 and snail1", "factors twist1 and snail1 that", "twist1 and snail1 that promote", "and snail1 that promote epithelial", "snail1 that promote epithelial mesenchymal", "that promote epithelial mesenchymal transition.", "promote epithelial mesenchymal transition. hif1", "epithelial mesenchymal transition. hif1 alpha", "mesenchymal transition. hif1 alpha and", "transition. hif1 alpha and hippo", "hif1 alpha and hippo signaling", "alpha and hippo signaling are", "and hippo signaling are mediated", "signaling are mediated respectively", "mediated respectively by", "respectively by binding of", "by binding of erbb4 to", "binding of erbb4 to hif1", "of erbb4 to hif1 alpha", "erbb4 to hif1 alpha and", "to hif1 alpha and to", "hif1 alpha and to yap", "and to yap paatero", "to yap paatero et", "yap paatero et al.", "paatero et al. 2012", "al. 2012 komuro", "2012 komuro et al.", "2003 . erbb4 increases activity", ". erbb4 increases activity of", "erbb4 increases activity of the", "increases activity of the transcription", "activity of the transcription factor", "of the transcription factor srebf2", "transcription factor srebf2 resulting", "factor srebf2 resulting in", "srebf2 resulting in increased", "resulting in increased expression of", "in increased expression of srebf2", "increased expression of srebf2 target", "expression of srebf2 target genes", "of srebf2 target genes involved", "srebf2 target genes involved in", "target genes involved in cholesterol", "genes involved in cholesterol biosynthesis.", "involved in cholesterol biosynthesis. the", "in cholesterol biosynthesis. the mechanism", "cholesterol biosynthesis. the mechanism is", "biosynthesis. the mechanism is not", "the mechanism is not known", "mechanism is not known and", "is not known and may", "not known and may involve", "known and may involve facilitation", "and may involve facilitation of", "may involve facilitation of srebf2", "involve facilitation of srebf2 cleavage", "facilitation of srebf2 cleavage through", "of srebf2 cleavage through erbb4", "srebf2 cleavage through erbb4 mediated", "cleavage through erbb4 mediated pi3k", "through erbb4 mediated pi3k signaling", "mediated pi3k signaling haskins", "pi3k signaling haskins et", "signaling haskins et al.", "haskins et al. 2016 .

in", "et al. 2016 .

in some", "al. 2016 .

in some contexts", ".

in some contexts erbb4", "some contexts erbb4 promotes", "contexts erbb4 promotes growth", "erbb4 promotes growth suppression or", "promotes growth suppression or apoptosis", "suppression or apoptosis penington", "or apoptosis penington et", "apoptosis penington et al.", "penington et al. 2002", "et al. 2002 .", "al. 2002 . activation", "2002 . activation of erbb4", ". activation of erbb4 in", "activation of erbb4 in breast", "of erbb4 in breast cancer", "erbb4 in breast cancer cell", "breast cancer cell lines leads", "cancer cell lines leads to", "cell lines leads to jnk", "lines leads to jnk dependent", "leads to jnk dependent increase", "to jnk dependent increase in", "jnk dependent increase in brca1", "dependent increase in brca1 mrna", "increase in brca1 mrna level", "in brca1 mrna level and", "brca1 mrna level and mitotic", "mrna level and mitotic cell", "level and mitotic cell cycle", "and mitotic cell cycle delay", "cell cycle delay but", "cycle delay but the", "delay but the exact", "but the exact mechanism has", "the exact mechanism has not", "exact mechanism has not been", "mechanism has not been elucidated", "not been elucidated muraoka", "been elucidated muraoka cook", "elucidated muraoka cook et", "muraoka cook et al. 2006", "cook et al. 2006 .", "et al. 2006 . the", "al. 2006 . the nature", "2006 . the nature of", ". the nature of growth", "the nature of growth responses", "nature of growth responses may", "of growth responses may be", "growth responses may be connected", "responses may be connected with", "may be connected with the", "be connected with the spliced", "connected with the spliced isoforms", "with the spliced isoforms expressed.", "the spliced isoforms expressed. in", "spliced isoforms expressed. in comparisons", "isoforms expressed. in comparisons of", "expressed. in comparisons of cyt1", "in comparisons of cyt1 vs", "comparisons of cyt1 vs cyt2", "cyt1 vs cyt2 full", "vs cyt2 full length", "cyt2 full length and", "length and icd expression", "and icd expression in", "icd expression in mammary", "in mammary cells cyt1", "mammary cells cyt1 was", "cells cyt1 was a", "cyt1 was a weaker growth", "was a weaker growth inducer", "weaker growth inducer associated", "growth inducer associated with", "inducer associated with attenuated", "associated with attenuated mapk signaling", "with attenuated mapk signaling relative", "attenuated mapk signaling relative to", "mapk signaling relative to cyt2", "relative to cyt2 wali", "to cyt2 wali et", "cyt2 wali et al.", "2014 . erbb4 s80 is", ". erbb4 s80 is also", "erbb4 s80 is also able", "s80 is also able to", "is also able to translocate", "also able to translocate to", "to translocate to the mitochondrial", "translocate to the mitochondrial matrix", "the mitochondrial matrix presumably", "mitochondrial matrix presumably when", "matrix presumably when its", "presumably when its nuclear translocation", "when its nuclear translocation is", "its nuclear translocation is inhibited.", "nuclear translocation is inhibited. once", "translocation is inhibited. once in", "is inhibited. once in the", "inhibited. once in the mitochondrion", "in the mitochondrion the", "the mitochondrion the bh3", "mitochondrion the bh3 domain", "the bh3 domain of erbb4", "domain of erbb4 characteristic", "of erbb4 characteristic of", "erbb4 characteristic of bcl2", "characteristic of bcl2 family members", "bcl2 family members may", "family members may enable", "members may enable it", "may enable it to act", "enable it to act as", "it to act as a", "to act as a pro", "act as a pro apoptotic", "as a pro apoptotic factor", "pro apoptotic factor naresh", "apoptotic factor naresh et", "factor naresh et al.", "naresh et al. 2006 .

erbb4", "et al. 2006 .

erbb4 plays", "al. 2006 .

erbb4 plays important", "2006 .

erbb4 plays important roles", ".

erbb4 plays important roles in", "plays important roles in the", "important roles in the developing", "roles in the developing and", "in the developing and adult", "the developing and adult nervous", "developing and adult nervous system.", "and adult nervous system. erbb4", "adult nervous system. erbb4 deficiency", "nervous system. erbb4 deficiency in", "system. erbb4 deficiency in somatostatin", "erbb4 deficiency in somatostatin expressing", "deficiency in somatostatin expressing neurons", "in somatostatin expressing neurons of", "somatostatin expressing neurons of the", "expressing neurons of the thalamic", "neurons of the thalamic reticular", "of the thalamic reticular nucleus", "the thalamic reticular nucleus alters", "thalamic reticular nucleus alters behaviors", "reticular nucleus alters behaviors dependent", "nucleus alters behaviors dependent on", "alters behaviors dependent on sensory", "behaviors dependent on sensory selection", "on sensory selection ahrens", "sensory selection ahrens et", "selection ahrens et al.", "ahrens et al. 2015 .", "et al. 2015 . nrg1", "al. 2015 . nrg1 activated", "2015 . nrg1 activated erbb4", ". nrg1 activated erbb4 signaling", "nrg1 activated erbb4 signaling enhances", "activated erbb4 signaling enhances ampa", "erbb4 signaling enhances ampa receptor", "signaling enhances ampa receptor responses", "enhances ampa receptor responses through", "ampa receptor responses through pkc", "receptor responses through pkc dependent", "responses through pkc dependent ampa", "through pkc dependent ampa receptor", "pkc dependent ampa receptor exocytosis.", "dependent ampa receptor exocytosis. this", "ampa receptor exocytosis. this results", "receptor exocytosis. this results in", "exocytosis. this results in an", "this results in an increased", "results in an increased excitatory", "in an increased excitatory input", "an increased excitatory input to", "increased excitatory input to parvalbumin", "excitatory input to parvalbumin expressing", "input to parvalbumin expressing inhibitory", "to parvalbumin expressing inhibitory neurons", "parvalbumin expressing inhibitory neurons in", "expressing inhibitory neurons in the", "inhibitory neurons in the visual", "neurons in the visual cortex", "in the visual cortex and", "the visual cortex and regulates", "visual cortex and regulates visual", "cortex and regulates visual cortical", "and regulates visual cortical plasticity", "visual cortical plasticity sun", "cortical plasticity sun et", "plasticity sun et al.", "sun et al. 2016 .", "et al. 2016 . nrg1", "al. 2016 . nrg1 activated", "2016 . nrg1 activated erbb4", "nrg1 activated erbb4 signaling is", "activated erbb4 signaling is involved", "erbb4 signaling is involved in", "signaling is involved in gabaergic", "is involved in gabaergic activity", "involved in gabaergic activity in", "in gabaergic activity in amygdala", "gabaergic activity in amygdala which", "activity in amygdala which mediates", "in amygdala which mediates fear", "amygdala which mediates fear conditioning", "mediates fear conditioning fear", "fear conditioning fear memory", "fear memory lu", "memory lu et", "lu et al. 2014 .", "et al. 2014 . conditional", "al. 2014 . conditional erbb4", "2014 . conditional erbb4 deletion", ". conditional erbb4 deletion from", "conditional erbb4 deletion from fast", "erbb4 deletion from fast spiking", "deletion from fast spiking interneurons", "fast spiking interneurons chandelier", "spiking interneurons chandelier and", "interneurons chandelier and basket", "chandelier and basket cells of", "and basket cells of the", "basket cells of the cerebral", "cells of the cerebral cortex", "of the cerebral cortex leads", "the cerebral cortex leads to", "cerebral cortex leads to synaptic", "cortex leads to synaptic defects", "leads to synaptic defects associated", "to synaptic defects associated with", "synaptic defects associated with increased", "defects associated with increased locomotor", "associated with increased locomotor activity", "with increased locomotor activity and", "increased locomotor activity and abnormal", "locomotor activity and abnormal emotional", "and abnormal emotional social", "abnormal emotional social and", "emotional social and cognitive", "social and cognitive function that", "and cognitive function that can", "cognitive function that can be", "function that can be linked", "that can be linked to", "can be linked to some", "be linked to some of", "linked to some of the", "to some of the schizophrenia", "some of the schizophrenia features.", "of the schizophrenia features. the", "the schizophrenia features. the level", "schizophrenia features. the level of", "features. the level of gad1", "level of gad1 gad67", "gad1 gad67 protein", "gad67 protein is reduced", "protein is reduced in the", "is reduced in the cortex", "reduced in the cortex of", "in the cortex of conditional", "the cortex of conditional erbb4", "cortex of conditional erbb4 mutants.", "of conditional erbb4 mutants. gad1", "conditional erbb4 mutants. gad1 is", "erbb4 mutants. gad1 is a", "mutants. gad1 is a gaba", "gad1 is a gaba synthesizing", "is a gaba synthesizing enzyme.", "a gaba synthesizing enzyme. cortical", "gaba synthesizing enzyme. cortical mrna", "synthesizing enzyme. cortical mrna levels", "enzyme. cortical mrna levels of", "cortical mrna levels of gad67", "mrna levels of gad67 are", "levels of gad67 are consistently", "of gad67 are consistently decreased", "gad67 are consistently decreased in", "are consistently decreased in schizophrenia", "decreased in schizophrenia del", "in schizophrenia del pino", "schizophrenia del pino et", "del pino et al. 2014", "pino et al. 2014 .", "et al. 2014 . erbb4", "al. 2014 . erbb4 is", "2014 . erbb4 is expressed", ". erbb4 is expressed in", "erbb4 is expressed in the", "is expressed in the gabaergic", "expressed in the gabaergic neurons", "in the gabaergic neurons of", "the gabaergic neurons of the", "gabaergic neurons of the bed", "neurons of the bed nucleus", "of the bed nucleus stria", "the bed nucleus stria terminalis", "nucleus stria terminalis a", "stria terminalis a part", "terminalis a part of", "a part of the extended", "part of the extended amygdala.", "of the extended amygdala. inhibition", "the extended amygdala. inhibition of", "extended amygdala. inhibition of nrg1", "amygdala. inhibition of nrg1 triggered", "inhibition of nrg1 triggered erbb4", "of nrg1 triggered erbb4 signaling", "nrg1 triggered erbb4 signaling induces", "triggered erbb4 signaling induces anxiety", "erbb4 signaling induces anxiety like", "signaling induces anxiety like behavior", "anxiety like behavior which", "like behavior which depends", "behavior which depends on", "which depends on gabaergic neurotransmission.", "depends on gabaergic neurotransmission. nrg1", "on gabaergic neurotransmission. nrg1 erbb4", "gabaergic neurotransmission. nrg1 erbb4 signaling", "neurotransmission. nrg1 erbb4 signaling stimulates", "nrg1 erbb4 signaling stimulates presynaptic", "erbb4 signaling stimulates presynaptic gaba", "signaling stimulates presynaptic gaba release", "presynaptic gaba release but", "gaba release but the", "release but the exact", "but the exact mechanism is", "the exact mechanism is not", "exact mechanism is not known", "is not known geng", "not known geng et", "known geng et al.", "geng et al. 2016 .", "al. 2016 . nrg1 protects", "2016 . nrg1 protects cortical", ". nrg1 protects cortical interneurons", "nrg1 protects cortical interneurons against", "protects cortical interneurons against ischemic", "cortical interneurons against ischemic brain", "interneurons against ischemic brain injury", "against ischemic brain injury through", "ischemic brain injury through erbb4", "brain injury through erbb4 mediated", "injury through erbb4 mediated increase", "through erbb4 mediated increase in", "erbb4 mediated increase in gabaergic", "mediated increase in gabaergic transmission", "in gabaergic transmission guan", "gabaergic transmission guan et", "transmission guan et al.", "guan et al. 2015 .", "et al. 2015 . nrg2", "al. 2015 . nrg2 activated", "2015 . nrg2 activated erbb4", ". nrg2 activated erbb4 can", "nrg2 activated erbb4 can reduce", "activated erbb4 can reduce the", "erbb4 can reduce the duration", "can reduce the duration of", "reduce the duration of gabaergic", "the duration of gabaergic transmission", "duration of gabaergic transmission by", "of gabaergic transmission by binding", "gabaergic transmission by binding to", "transmission by binding to gaba", "by binding to gaba receptors", "binding to gaba receptors at", "to gaba receptors at the", "gaba receptors at the postsynaptic", "receptors at the postsynaptic membrane", "at the postsynaptic membrane via", "the postsynaptic membrane via their", "postsynaptic membrane via their gabra1", "membrane via their gabra1 subunit", "via their gabra1 subunit and", "their gabra1 subunit and promoting", "gabra1 subunit and promoting endocytosis", "subunit and promoting endocytosis of", "and promoting endocytosis of gaba", "promoting endocytosis of gaba receptors", "of gaba receptors mitchell", "gaba receptors mitchell et", "receptors mitchell et al.", "mitchell et al. 2013 .", "et al. 2013 . nrg1", "al. 2013 . nrg1 promotes", "2013 . nrg1 promotes synchronization", ". nrg1 promotes synchronization of", "nrg1 promotes synchronization of prefrontal", "promotes synchronization of prefrontal cortex", "synchronization of prefrontal cortex interneurons", "of prefrontal cortex interneurons in", "prefrontal cortex interneurons in an", "cortex interneurons in an erbb4", "interneurons in an erbb4 dependent", "in an erbb4 dependent manner", "erbb4 dependent manner hou", "dependent manner hou et", "manner hou et al.", "hou et al. 2014 .", "et al. 2014 . nrg1", "al. 2014 . nrg1 erbb4", "2014 . nrg1 erbb4 signaling", ". nrg1 erbb4 signaling protects", "nrg1 erbb4 signaling protects neurons", "erbb4 signaling protects neurons from", "signaling protects neurons from the", "protects neurons from the cell", "neurons from the cell death", "from the cell death induced", "the cell death induced by", "cell death induced by a", "death induced by a mutant", "induced by a mutant form", "by a mutant form of", "a mutant form of the", "mutant form of the amyloid", "form of the amyloid precursor", "of the amyloid precursor protein", "amyloid precursor protein app", "app woo et", "woo et al. 2012 .

clinical", "et al. 2012 .

clinical relevance", "al. 2012 .

clinical relevance of", "2012 .

clinical relevance of erbb4", ".

clinical relevance of erbb4 has", "relevance of erbb4 has been", "of erbb4 has been identified", "erbb4 has been identified in", "has been identified in several", "been identified in several contexts.", "identified in several contexts. in", "in several contexts. in cancer", "contexts. in cancer putative", "in cancer putative and", "cancer putative and validated", "putative and validated gain of", "and validated gain of function", "validated gain of function mutations", "gain of function mutations or", "of function mutations or gene", "function mutations or gene amplification", "mutations or gene amplification that", "or gene amplification that may", "gene amplification that may be", "amplification that may be drivers", "that may be drivers have", "may be drivers have been", "be drivers have been identified", "drivers have been identified at", "have been identified at modest", "been identified at modest frequencies", "at modest frequencies and", "modest frequencies and may", "frequencies and may also", "and may also contribute to", "may also contribute to resistance", "also contribute to resistance to", "contribute to resistance to egfr", "to resistance to egfr and", "resistance to egfr and erbb2", "to egfr and erbb2 targeted", "egfr and erbb2 targeted therapies.", "and erbb2 targeted therapies. this", "erbb2 targeted therapies. this is", "targeted therapies. this is noteworthy", "therapies. this is noteworthy as", "this is noteworthy as erbb4", "is noteworthy as erbb4 kinase", "noteworthy as erbb4 kinase activity", "as erbb4 kinase activity is", "erbb4 kinase activity is inhibited", "kinase activity is inhibited by", "activity is inhibited by pan", "is inhibited by pan erbb", "inhibited by pan erbb tyrosine", "by pan erbb tyrosine kinase", "pan erbb tyrosine kinase inhibitors", "tyrosine kinase inhibitors including", "kinase inhibitors including lapatinib", "including lapatinib which is", "lapatinib which is approved", "which is approved by the", "is approved by the us", "approved by the us fda.", "by the us fda. the", "the us fda. the reduced", "us fda. the reduced prevalence", "fda. the reduced prevalence relative", "the reduced prevalence relative to", "reduced prevalence relative to egfr", "prevalence relative to egfr and", "relative to egfr and erbb2", "to egfr and erbb2 in", "egfr and erbb2 in cancer", "and erbb2 in cancer may", "erbb2 in cancer may reflect", "in cancer may reflect more", "cancer may reflect more restricted", "may reflect more restricted expression", "reflect more restricted expression of", "more restricted expression of erbb4", "expression of erbb4 or", "of erbb4 or differential", "erbb4 or differential signaling", "or differential signaling as", "differential signaling as specific", "signaling as specific erbb4", "as specific erbb4 isoforms have", "specific erbb4 isoforms have been", "erbb4 isoforms have been linked", "isoforms have been linked to", "have been linked to growth", "been linked to growth inhibition", "linked to growth inhibition or", "to growth inhibition or apoptosis", "growth inhibition or apoptosis in", "inhibition or apoptosis in experimental", "or apoptosis in experimental systems.", "apoptosis in experimental systems. erbb2/erbb4", "in experimental systems. erbb2/erbb4 heterodimers", "experimental systems. erbb2/erbb4 heterodimers protect", "systems. erbb2/erbb4 heterodimers protect cardiomyocytes", "heterodimers protect cardiomyocytes so", "protect cardiomyocytes so reduced", "cardiomyocytes so reduced activity", "so reduced activity of erbb4", "reduced activity of erbb4 in", "activity of erbb4 in patients", "of erbb4 in patients treated", "erbb4 in patients treated with", "in patients treated with the", "patients treated with the erbb2", "treated with the erbb2 targeted", "with the erbb2 targeted therapeutic", "the erbb2 targeted therapeutic antibody", "erbb2 targeted therapeutic antibody trastuzumab", "targeted therapeutic antibody trastuzumab may", "therapeutic antibody trastuzumab may contribute", "antibody trastuzumab may contribute to", "trastuzumab may contribute to the", "may contribute to the cardiotoxicity", "contribute to the cardiotoxicity of", "to the cardiotoxicity of this", "the cardiotoxicity of this agent", "cardiotoxicity of this agent when", "of this agent when used", "this agent when used in", "agent when used in combination", "when used in combination with", "in combination with cardiotoxic", "with cardiotoxic anthracyclines.

with", "cardiotoxic anthracyclines.

with the importance", "anthracyclines.

with the importance of erbb4", "the importance of erbb4 in", "importance of erbb4 in developing", "of erbb4 in developing and", "erbb4 in developing and adult", "in developing and adult nervous", "developing and adult nervous system", "adult nervous system nrg1", "nervous system nrg1 and/or", "system nrg1 and/or erbb4", "and/or erbb4 polymorphisms splicing", "erbb4 polymorphisms splicing aberrations", "polymorphisms splicing aberrations and", "splicing aberrations and mutations have", "aberrations and mutations have been", "and mutations have been linked", "mutations have been linked to", "have been linked to nervous", "been linked to nervous system", "linked to nervous system disorders", "to nervous system disorders including", "nervous system disorders including schizophrenia", "system disorders including schizophrenia and", "disorders including schizophrenia and amyotrophic", "including schizophrenia and amyotrophic lateral", "schizophrenia and amyotrophic lateral sclerosis", "amyotrophic lateral sclerosis although", "lateral sclerosis although these", "sclerosis although these findings", "although these findings are not", "these findings are not yet", "findings are not yet definitive." ] }, { "record_id": "GLY_000594_1_31", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1236974", "r hsa", "hsa 1236974", "r hsa 1236974" ] }, { "record_id": "GLY_000594_1_31", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "er phagosome", "phagosome pathway", "er phagosome pathway", "the other", "other tap", "tap dependent", "dependent cross", "cross presentation", "presentation mechanism", "mechanism in", "in phagocytes", "phagocytes is", "is the", "the endoplasmic", "endoplasmic reticulum", "phagosome model.", "model. desjardins", "desjardins proposed", "proposed that", "that er", "er is", "is recruited", "recruited to", "to the", "the cell", "cell surface", "where it", "it fuses", "fuses with", "with the", "the plasma", "plasma membrane", "underneath phagocytic", "phagocytic cups", "to supply", "supply membrane", "membrane for", "for the", "the formation", "formation of", "of nascent", "nascent phagosomes", "gagnon et", "et al.", "al. 2002", "2002 .", ". three", "three independent", "independent studies", "studies simultaneously", "simultaneously showed", "showed that", "er contributes", "contributes to", "the vast", "vast majority", "majority of", "of phagosome", "phagosome membrane", "guermonprez et", "al. 2003", "houde et", "ackerman et", "2003 .", ". the", "the composition", "composition of", "of early", "early phagosome", "membrane contains", "contains er", "er resident", "resident proteins", "the components", "components required", "required for", "for cross", "cross presentation.", "presentation. this", "this model", "model is", "is similar", "similar to", "the phagosome", "phagosome to", "to cytosol", "cytosol model", "model in", "in that", "that ag", "ag is", "is translocated", "translocated to", "cytosol for", "for proteasomal", "proteasomal degradation", "but differs", "differs in", "that antigenic", "antigenic peptides", "peptides are", "are translocated", "translocated back", "back into", "into the", "instead of", "of er", "for peptide:mhc", "peptide:mhc i", "i complexes.", "complexes. er", "er fusion", "fusion with", "with phagosome", "phagosome introduces", "introduces molecules", "molecules that", "that are", "are involved", "involved in", "in ag", "ag transport", "transport to", "and proteasome", "proteasome generated", "generated peptides", "peptides back", "for loading", "loading onto", "onto mhc", "mhc i.", "i.
although", "
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"GLY_000594_1_33", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1250196", "r hsa", "hsa 1250196", "r hsa 1250196" ] }, { "record_id": "GLY_000594_1_33", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc1 events", "events in", "in erbb2", "erbb2 signaling", "shc1 events in", "events in erbb2", "in erbb2 signaling", "shc1 events in erbb2", "events in erbb2 signaling", "shc1 events in erbb2 signaling", "all erbb2", "erbb2 heterodimers", "erbb2:erbb3 and", "and erbb2:erbb4", "are able", "able to", "to activate", "activate raf/map", "raf/map kinase", "kinase cascade", "cascade by", "by recruiting", "recruiting shc1", "pinkas kramarski", "kramarski et", "et al.", "al. 1996", "sepp lorenzino", "lorenzino et", "to phosphorylated", "phosphorylated c", "c tail", "tail tyrosine", "tyrosine residues", "residues in", "in either", "either egfr", "y1148 and", "and y1173", "y1222 and", "and y1248", "or 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al.", "et al. 1993", "1993 soler", "soler et al.", "et al. 1994", "and the phosphorylated", "the phosphorylated shc1", "phosphorylated shc1 recruits", "shc1 recruits grb2:sos1", "recruits grb2:sos1 complex", "complex xie", "xie et al.", "et al. 1995", "which leads to", "leads to sos1", "to sos1 mediated", "sos1 mediated guanyl", "mediated guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange on", "exchange on ras", "ras xie", "1995 and", "and downstream activation", "downstream activation of", "activation of raf", "of raf and", "raf and map", "and map kinases.", "erbb2 heterodimers erbb2:egfr", "erbb2:egfr erbb2:erbb3 and", "and erbb2:erbb4 are", "erbb2:erbb4 are able", "are able to activate", "able to activate raf/map", "to activate raf/map kinase", "activate raf/map kinase cascade", "raf/map kinase cascade by", "kinase cascade by recruiting", "cascade by recruiting shc1", "recruiting shc1 pinkas", "shc1 pinkas kramarski", "pinkas kramarski et al.", "kramarski et al. 1996", "al. 1996 sepp", "1996 sepp lorenzino", "sepp lorenzino et al.", "lorenzino et al. 1996", "al. 1996 to", "1996 to phosphorylated", "to phosphorylated c tail", "phosphorylated c tail tyrosine", "c tail tyrosine residues", "tail tyrosine residues in", "tyrosine residues in either", "residues in either egfr", "either egfr y1148", "egfr y1148 and", "y1173 erbb2", "y1221 y1222 and", "y1248 erbb3", "y1328 or erbb4", "or erbb4 y1188", "erbb4 y1188 and", "y1188 and y1242 in", "and y1242 in jm", "y1242 in jm a", "in jm a cyt1", "jm a cyt1 isoform", "cyt1 isoform y1178", "isoform y1178 and", "y1178 and y1232 in", "and y1232 in jm", "y1232 in jm b", "in jm b cyt1", "jm b cyt1 isoform", "cyt1 isoform y1172", "isoform y1172 and", "y1172 and y1226 in", "and y1226 in jm", "y1226 in jm a", "in jm a cyt2", "jm a cyt2 isoform", "a cyt2 isoform .", "cyt2 isoform . shc1", "isoform . shc1 recruitment", ". shc1 recruitment is", "shc1 recruitment is followed", "recruitment is followed by", "is followed by phosphorylation", "by phosphorylation segatto", "phosphorylation segatto et", "segatto et al. 1993", "al. 1993 soler", "1993 soler et", "soler et al. 1994", "1994 and", "and the phosphorylated shc1", "the phosphorylated shc1 recruits", "phosphorylated shc1 recruits grb2:sos1", "shc1 recruits grb2:sos1 complex", "grb2:sos1 complex xie", "complex xie et", "xie et al. 1995", "1995 which", "which leads to sos1", "leads to sos1 mediated", "to sos1 mediated guanyl", "sos1 mediated guanyl nucleotide", "mediated guanyl nucleotide exchange", "guanyl nucleotide exchange on", "nucleotide exchange on ras", "on ras xie", "ras xie et", "al. 1995 and", "1995 and downstream", "and downstream activation of", "downstream activation of raf", "activation of raf and", "of raf and map", "raf and map kinases.", "all erbb2 heterodimers erbb2:egfr", "heterodimers erbb2:egfr erbb2:erbb3", "erbb2:egfr erbb2:erbb3 and erbb2:erbb4", "erbb2:erbb3 and erbb2:erbb4 are", "and erbb2:erbb4 are able", "erbb2:erbb4 are able to", "are able to activate raf/map", "able to activate raf/map kinase", "to activate raf/map kinase cascade", "activate raf/map kinase cascade by", "raf/map kinase cascade by recruiting", "kinase cascade by recruiting shc1", "by recruiting shc1 pinkas", "recruiting shc1 pinkas kramarski", "shc1 pinkas kramarski et", "pinkas kramarski et al. 1996", "et al. 1996 sepp", "al. 1996 sepp lorenzino", "1996 sepp lorenzino et", "sepp lorenzino et al. 1996", "et al. 1996 to", "al. 1996 to phosphorylated", "1996 to phosphorylated c", "to phosphorylated c tail tyrosine", "phosphorylated c tail tyrosine residues", "c tail tyrosine residues in", "tail tyrosine residues in either", "tyrosine residues in either egfr", "in either egfr y1148", "either egfr y1148 and", "egfr y1148 and y1173", "and y1173 erbb2", "erbb2 y1196 y1221", "y1196 y1221 y1222", "y1221 y1222 and y1248", "and y1248 erbb3", "erbb3 y1328 or", "or erbb4 y1188 and", "erbb4 y1188 and y1242", "y1188 and y1242 in 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complex xie", "grb2:sos1 complex xie et", "complex xie et al.", "al. 1995 which", "1995 which leads", "which leads to sos1 mediated", "leads to sos1 mediated guanyl", "to sos1 mediated guanyl nucleotide", "sos1 mediated guanyl nucleotide exchange", "mediated guanyl nucleotide exchange on", "guanyl nucleotide exchange on ras", "exchange on ras xie", "on ras xie et", "ras xie et al.", "et al. 1995 and", "al. 1995 and downstream", "1995 and downstream activation", "and downstream activation of raf", "downstream activation of raf and", "activation of raf and map", "of raf and map kinases." ] }, { "record_id": "GLY_000594_1_34", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1250342", "r hsa", "hsa 1250342", "r hsa 1250342" ] }, { "record_id": "GLY_000594_1_34", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi3k events", "events in", "in erbb4", "erbb4 signaling", "pi3k events in", "events in 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"enables it to recruit", "it to recruit the", "to recruit the complex", "recruit the complex of", "the complex of grb2", "complex of grb2 and", "of grb2 and sos1", "and sos1 resulting", "sos1 resulting in", "resulting in the guanyl", "in the guanyl nucleotide", "the guanyl nucleotide exchange", "guanyl nucleotide exchange on", "nucleotide exchange on ras", "exchange on ras and", "on ras and activation", "ras and activation of", "and activation of raf", "activation of raf and", "of raf and map", "raf and map kinase", "and map kinase cascade", "kinase cascade kainulainen", "cascade kainulainen et", "kainulainen et al. 2000", "et al. 2000 .", "all splicing isoforms of erbb4", "splicing isoforms of erbb4 possess", "isoforms of erbb4 possess two", "of erbb4 possess two tyrosine", "erbb4 possess two tyrosine residues", "possess two tyrosine residues in", "two tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "in the c tail that", "the c tail that serve", "c tail that serve as", "tail that serve as docking", "that serve as docking sites", "serve as docking sites for", "as docking sites for shc1", "sites for shc1 kaushansky", "for shc1 kaushansky et", "shc1 kaushansky et al.", "et al. 2008 pinkas", "al. 2008 pinkas kramarski", "2008 pinkas kramarski et", "pinkas kramarski et al. 1996", "et al. 1996 cohen", "al. 1996 cohen et", "1996 cohen et al.", "cohen et al. 1996 .", "et al. 1996 . once", "al. 1996 . once bound", "1996 . once bound to", ". once bound to erbb4", "bound to erbb4 shc1", "to erbb4 shc1 becomes", "erbb4 shc1 becomes phosphorylated", "shc1 becomes phosphorylated on tyrosine", "becomes phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues by", "on tyrosine residues by the", "tyrosine residues by the tyrosine", "residues by the tyrosine kinase", "by the tyrosine kinase activity", "the tyrosine kinase activity of", "tyrosine kinase activity of erbb4", "activity of erbb4 which", "of erbb4 which enables", "erbb4 which enables it", "which enables it to recruit", "enables it to recruit the", "it to recruit the complex", "to recruit the complex of", "recruit the complex of grb2", "the complex of grb2 and", "complex of grb2 and sos1", "grb2 and sos1 resulting", "and sos1 resulting in", "sos1 resulting in the", "resulting in the guanyl nucleotide", "in the guanyl nucleotide exchange", "the guanyl nucleotide exchange on", "guanyl nucleotide exchange on ras", "nucleotide exchange on ras and", "exchange on ras and activation", "on ras and activation of", "ras and activation of raf", "and activation of raf and", "activation of raf and map", "of raf and map kinase", "raf and map kinase cascade", "map kinase cascade kainulainen", "kinase cascade kainulainen et", "cascade kainulainen et al.", "kainulainen et al. 2000 ." ] }, { "record_id": "GLY_000594_1_36", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1251985", "r hsa", "hsa 1251985", "r hsa 1251985" ] }, { "record_id": "GLY_000594_1_36", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nuclear signaling", "signaling by", "by erbb4", "nuclear signaling by", "signaling by erbb4", "nuclear signaling by erbb4", "besides signaling", "signaling as", "as a", "a transmembrane", "transmembrane receptor", "ligand activated", "activated homodimers", "homodimers of", "of erbb4", "erbb4 jm", "jm a", "a isoforms", "a cyt1", "cyt1 and", "and erbb4", "a cyt2", "undergo proteolytic", "proteolytic cleavage", "cleavage by", "by adam17", "in the", "the juxtamembrane", "juxtamembrane region", "resulting in", "in shedding", "shedding of", "of the", "the extracellular", "extracellular domain", "domain and", "and formation", "formation of", "of an", "an 80", "80 kda", "kda membrane", "membrane bound", "bound erbb4", "erbb4 fragment", "fragment known", "known as", "as erbb4", "erbb4 m80", "rio et", "et al.", "al. 2000", "cheng et", "al. 2003", "2003 .", ". erbb4", "m80 undergoes", "undergoes further", "further proteolytic", "mediated by", "by the", "the gamma", "gamma secretase", "secretase complex", "which releases", "releases the", "the soluble", "soluble 80", "kda erbb4", "erbb4 intracellular", "intracellular domain", "erbb4 s80", "s80 or", "or e4icd", "into the", "the cytosol", "ni et", "al. 2001", "2001 .", "s80 is", "is able", "able to", "to translocate", "translocate to", "to the", "the nucleus", "promote nuclear", "nuclear translocation", "translocation of", "of various", "various transcription", "transcription factors", "and act", "act as", "a transcription", "transcription co", "co factor.", "factor. in", "in neuronal", "neuronal precursors", "s80 binds", "binds the", "the complex", "complex of", "of tab", "tab and", "and ncor1", "helps to", "to move", "move the", "complex into", "and is", "is a", "a co", "co factor", "factor of", "of tab:ncor1", "tab:ncor1 mediated", "mediated inhibition", "inhibition of", "of expression", "expression of", "of astrocyte", "astrocyte differentiation", "differentiation genes", "genes gfap", "gfap and", "and s100b", "sardi et", "al. 2006", "2006 .", ". in", "in mammary", "mammary cells", "s80 recruits", "recruits stat5a", "stat5a transcription", "transcription factor", "factor in", "shuttles it", "it to", "and acts", "acts as", "as the", "the stat5a", "stat5a co", "in binding", "binding to", "to and", "and promoting", "promoting transcription", "transcription from", "from the", "the beta", "beta casein", "and may", "may be", "be involved", "involved in", "the regulation", "regulation of", "of other", "other lactation", "lactation related", "related genes", "williams et", "al. 2004", "muraoka cook", "cook et", "al. 2008", "2008 .", "s80 was", "was also", "also shown", "shown to", "to bind", "bind activated", "activated estrogen", "estrogen receptor", "receptor in", "nucleus and", "as its", "its transcriptional", "transcriptional co", "in promoting", "transcription of", "of some", "some estrogen", "estrogen regulated", "regulated genes", "such as", "as progesterone", "progesterone receptor", "receptor gene", "gene nr3c3", "nr3c3 and", "and cxcl12", "cxcl12 i.e.", "i.e. sdf1", "zhu et", ". erbb4s80", "erbb4s80 may", "may inhibit", "inhibit transcription", "of telomerase", "telomerase reverse", "reverse transcriptase", "by increasing", "increasing methylation", "methylation of", "the tert", "tert gene", "gene promoter", "promoter through", "through an", "an unknown", "unknown mechanism", "ishibashi et", "al. 2012", "2012 .

the", ".

the c", "c tail", "tail of", "erbb4 possesses", "possesses several", "several ww", "ww domain", "domain binding", "binding motifs", "three in", "in cyt1", "cyt1 isoform", "isoform and", "and two", "two in", "in cyt2", "cyt2 isoform", "which enable", "enable interaction", "interaction of", "erbb4 with", "with ww", "domain containing", "containing proteins.", "proteins. erbb4", "through ww", "interacts with", "with yap1", "yap1 transcription", "a known", "known proto", "proto oncogene", "be a", "co regulator", "regulator of", "of yap1", "yap1 mediated", "mediated transcription", "komuro et", "omerovic et", "2004 .", ". the", "the tumor", "tumor suppressor", "suppressor wwox", "another ww", "containing protein", "competes with", "yap1 in", "to erbb4", "s80 and", "and prevents", "prevents translocation", "s80 to", "aqeilan et", "al. 2005", "2005 .", "is also", "also able", "the mitochondrial", "mitochondrial matrix", "presumably when", "when its", "its nuclear", "translocation is", "is inhibited.", "inhibited. once", "once in", "the mitochondrion", "the bh3", "bh3 domain", "domain of", "characteristic of", "of bcl2", "bcl2 family", "family members", "may enable", "enable it", "to act", "a pro", "pro apoptotic", "apoptotic factor", "naresh et", "besides signaling as", "signaling as a", "as a transmembrane", "a transmembrane receptor", "receptor ligand", "ligand activated homodimers", "activated homodimers of", "homodimers of erbb4", "of erbb4 jm", "erbb4 jm a", "jm a isoforms", "isoforms erbb4", "jm a cyt1", "a cyt1 and", "cyt1 and erbb4", "and erbb4 jm", "jm a cyt2", "cyt2 undergo", "undergo proteolytic cleavage", "proteolytic cleavage by", "cleavage by adam17", "adam17 tace", "tace in", "in the juxtamembrane", "the juxtamembrane region", "region resulting", "resulting in shedding", "in shedding of", "shedding of the", "of the extracellular", "the extracellular domain", "extracellular domain and", "domain and formation", "and formation of", "formation of an", "of an 80", "an 80 kda", "80 kda membrane", "kda membrane bound", "membrane bound erbb4", "bound erbb4 fragment", "erbb4 fragment known", "fragment known as", "known as erbb4", "as erbb4 m80", "m80 rio", "rio et al.", "et al. 2000", "2000 cheng", "cheng et al.", "et al. 2003", "al. 2003 .", "2003 . erbb4", ". erbb4 m80", "erbb4 m80 undergoes", "m80 undergoes further", "undergoes further proteolytic", "further proteolytic cleavage", "cleavage mediated", "mediated by the", "by the gamma", "the gamma secretase", "gamma secretase complex", "complex which", "which releases the", "releases the soluble", "the soluble 80", "soluble 80 kda", "80 kda erbb4", "kda erbb4 intracellular", "erbb4 intracellular domain", "domain known", "as erbb4 s80", "erbb4 s80 or", "s80 or e4icd", "e4icd into", "into the cytosol", "cytosol ni", "ni et al.", "et al. 2001", "al. 2001 .", "2001 . erbb4", ". erbb4 s80", "erbb4 s80 is", "s80 is able", "is able to", "able to translocate", "to translocate to", "translocate to the", "to the nucleus", "nucleus promote", "promote nuclear translocation", "nuclear translocation of", "translocation of various", "of various transcription", "various transcription factors", "factors and", "and act as", "act as a", "as a transcription", "a transcription co", "transcription co factor.", "co factor. in", "factor. in neuronal", "in neuronal precursors", "precursors erbb4", "erbb4 s80 binds", "s80 binds the", "binds the complex", "the complex of", "complex of tab", "of tab and", "tab and ncor1", "ncor1 helps", "helps to move", "to move the", "move the complex", "the complex into", "complex into the", "into the nucleus", "and is a", "is a co", "a co factor", "co factor of", "factor of tab:ncor1", "of tab:ncor1 mediated", "tab:ncor1 mediated inhibition", "mediated inhibition of", "inhibition of expression", "of expression of", "expression of astrocyte", "of astrocyte differentiation", "astrocyte differentiation genes", "differentiation genes gfap", "genes gfap and", "gfap and s100b", "s100b sardi", "sardi et al.", "et al. 2006", "al. 2006 .", "2006 . in", ". in mammary", "in mammary cells", "cells erbb4", "erbb4 s80 recruits", "s80 recruits stat5a", "recruits stat5a transcription", "stat5a transcription factor", "transcription factor in", "factor in the", "in the cytosol", "cytosol shuttles", "shuttles it to", "it to the", "and acts as", "acts as the", "as the stat5a", "the stat5a co", "stat5a co factor", "co factor in", "factor in binding", "in binding to", "binding to and", "to and promoting", "and promoting transcription", "promoting transcription from", "transcription from the", "from the beta", "the beta casein", "casein csn2", "csn2 promoter", "promoter and", "and may be", "may be involved", "be involved in", "involved in the", "in the regulation", "the regulation of", "regulation of other", "of other lactation", "other lactation related", "lactation related genes", "genes williams", "williams et al.", "et al. 2004", "2004 muraoka", "muraoka cook et", "cook et al.", "et al. 2008", "al. 2008 .", "2008 . erbb4", "erbb4 s80 was", "s80 was also", "was also shown", "also shown to", "shown to bind", "to bind activated", "bind activated estrogen", "activated estrogen receptor", "estrogen receptor in", "receptor in the", "in the nucleus", "the nucleus and", "nucleus and act", "act as its", "as its transcriptional", "its transcriptional co", "transcriptional co factor", "factor in promoting", "in promoting transcription", "promoting transcription of", "transcription of some", "of some estrogen", "some estrogen regulated", "estrogen regulated genes", "genes such", "such as progesterone", "as progesterone receptor", "progesterone receptor gene", "receptor gene nr3c3", "gene nr3c3 and", "nr3c3 and cxcl12", "and cxcl12 i.e.", "cxcl12 i.e. sdf1", "sdf1 zhu", "zhu et al.", "2006 . erbb4s80", ". erbb4s80 may", "erbb4s80 may inhibit", "may inhibit transcription", "inhibit transcription of", "transcription of telomerase", "of telomerase reverse", "telomerase reverse transcriptase", "transcriptase tert", "tert by", "by increasing methylation", "increasing methylation of", "methylation of the", "of the tert", "the tert gene", "tert gene promoter", "gene promoter through", "promoter through an", "through an unknown", "an unknown mechanism", "mechanism ishibashi", "ishibashi et al.", "et al. 2012", "al. 2012 .

the", "2012 .

the c", ".

the c tail", "c tail of", "tail of erbb4", "of erbb4 possesses", "erbb4 possesses several", "possesses several ww", "several ww domain", "ww domain binding", "domain binding motifs", "motifs three", "three in cyt1", "in cyt1 isoform", "cyt1 isoform and", "isoform and two", "and two in", "two in cyt2", "in cyt2 isoform", "which enable interaction", "enable interaction of", "interaction of erbb4", "of erbb4 with", "erbb4 with ww", "with ww domain", "ww domain containing", "domain containing proteins.", "containing proteins. erbb4", "proteins. erbb4 s80", "s80 through", "through ww domain", "motifs interacts", "interacts with yap1", "with yap1 transcription", "yap1 transcription factor", "factor a", "a known proto", "known proto oncogene", "oncogene and", "may be a", "be a co", "a co regulator", "co regulator of", "regulator of yap1", "of yap1 mediated", "yap1 mediated transcription", "transcription komuro", "komuro et al.", "2003 omerovic", "omerovic et al.", "al. 2004 .", "2004 . the", ". the tumor", "the tumor suppressor", "tumor suppressor wwox", "wwox another", "another ww domain", "domain containing protein", "protein competes", "competes with yap1", "with yap1 in", "yap1 in binding", "binding to erbb4", "to erbb4 s80", "erbb4 s80 and", "s80 and prevents", "and prevents translocation", "prevents translocation of", "translocation of erbb4", "of erbb4 s80", "erbb4 s80 to", "s80 to the", "nucleus aqeilan", "aqeilan et al.", "et al. 2005", "al. 2005 .", "2005 . erbb4", "s80 is also", "is also able", "also able to", "to the mitochondrial", "the mitochondrial matrix", "matrix presumably", "presumably when its", "when its nuclear", "its nuclear translocation", "nuclear translocation is", "translocation is inhibited.", "is inhibited. once", "inhibited. once in", "once in the", "in the mitochondrion", "mitochondrion the", "the bh3 domain", "bh3 domain of", "domain of erbb4", "erbb4 characteristic", "characteristic of bcl2", "of bcl2 family", "bcl2 family members", "members may", "may enable it", "enable it to", "it to act", "to act as", "as a pro", "a pro apoptotic", "pro apoptotic factor", "factor naresh", "naresh et al.", "besides signaling as a", "signaling as a transmembrane", "as a transmembrane receptor", "transmembrane receptor ligand", "receptor ligand activated", "ligand activated homodimers of", "activated homodimers of erbb4", "homodimers of erbb4 jm", "of erbb4 jm a", "erbb4 jm a isoforms", "a isoforms erbb4", "isoforms erbb4 jm", "erbb4 jm a cyt1", "jm a cyt1 and", "a cyt1 and erbb4", "cyt1 and erbb4 jm", "and erbb4 jm a", "erbb4 jm a cyt2", "a cyt2 undergo", "cyt2 undergo proteolytic", "undergo proteolytic cleavage by", "proteolytic cleavage by adam17", "by adam17 tace", "tace in the", "in the juxtamembrane region", "juxtamembrane region resulting", "region resulting in", "resulting in shedding of", "in shedding of the", "shedding of the extracellular", "of the extracellular domain", "the extracellular domain and", "extracellular domain and formation", "domain and formation of", "and formation of an", "formation of an 80", "of an 80 kda", "an 80 kda membrane", "80 kda membrane bound", "kda membrane bound erbb4", "membrane bound erbb4 fragment", "bound erbb4 fragment known", "erbb4 fragment known as", "fragment known as erbb4", "known as erbb4 m80", "erbb4 m80 rio", "m80 rio et", "rio et al. 2000", "al. 2000 cheng", "2000 cheng et", "cheng et al. 2003", "et al. 2003 .", "al. 2003 . erbb4", "2003 . erbb4 m80", ". erbb4 m80 undergoes", "erbb4 m80 undergoes further", "m80 undergoes further proteolytic", "undergoes further proteolytic cleavage", "proteolytic cleavage mediated", "cleavage mediated by", "mediated by the gamma", "by the gamma secretase", "the gamma secretase complex", "secretase complex which", "complex which releases", "which releases the soluble", "releases the soluble 80", "the soluble 80 kda", "soluble 80 kda erbb4", "80 kda erbb4 intracellular", "kda erbb4 intracellular domain", "intracellular domain known", "domain known as", "known as erbb4 s80", "as erbb4 s80 or", "erbb4 s80 or e4icd", "or e4icd into", "e4icd into the", "the cytosol ni", "cytosol ni et", "ni et al. 2001", "et al. 2001 .", "al. 2001 . erbb4", "2001 . erbb4 s80", ". erbb4 s80 is", "erbb4 s80 is able", "s80 is able to", "is able to translocate", "able to translocate to", "to translocate to the", "translocate to the nucleus", "the nucleus promote", "nucleus promote nuclear", "promote nuclear translocation of", "nuclear translocation of various", "translocation of various transcription", "of various transcription factors", "transcription factors and", "factors and act", "and act as a", "act as a transcription", "as a transcription co", "a transcription co factor.", "transcription co factor. in", "co factor. in neuronal", "factor. in neuronal precursors", "neuronal precursors erbb4", "precursors erbb4 s80", "erbb4 s80 binds the", "s80 binds the complex", "binds the complex of", "the complex of tab", "complex of tab and", "of tab and ncor1", "and ncor1 helps", "ncor1 helps to", "helps to move the", "to move the complex", "move the complex into", "the complex into the", "complex into the nucleus", "nucleus and is", "and is a co", "is a co factor", "a co factor of", "co factor of tab:ncor1", "factor of tab:ncor1 mediated", "of tab:ncor1 mediated inhibition", "tab:ncor1 mediated inhibition of", "mediated inhibition of expression", "inhibition of expression of", "of expression of astrocyte", "expression of astrocyte differentiation", "of astrocyte differentiation genes", "astrocyte differentiation genes gfap", "differentiation genes gfap and", "genes gfap and s100b", "and s100b sardi", "s100b sardi et", "sardi et al. 2006", "et al. 2006 .", "al. 2006 . in", "2006 . in mammary", ". in mammary cells", "mammary cells erbb4", "cells erbb4 s80", "erbb4 s80 recruits stat5a", "s80 recruits stat5a transcription", "recruits stat5a transcription factor", "stat5a transcription factor in", "transcription factor in the", "factor in the cytosol", "the cytosol shuttles", "cytosol shuttles it", "shuttles it to the", "it to the nucleus", "nucleus and acts", "and acts as the", "acts as the stat5a", "as the stat5a co", "the stat5a co factor", "stat5a co factor in", "co factor in binding", "factor in binding to", "in binding to and", "binding to and promoting", "to and promoting transcription", "and promoting transcription from", "promoting transcription from the", "transcription from the beta", "from the beta casein", "beta casein csn2", "promoter and may", "and may be involved", "may be involved in", "be involved in the", "involved in the regulation", "in the regulation of", "the regulation of other", "regulation of other lactation", "of other lactation related", "other lactation related genes", "related genes williams", "genes williams et", "williams et al. 2004", "al. 2004 muraoka", "2004 muraoka cook", "muraoka cook et al.", "cook et al. 2008", "et al. 2008 .", "al. 2008 . erbb4", "2008 . erbb4 s80", ". erbb4 s80 was", "erbb4 s80 was also", "s80 was also shown", "was also shown to", "also shown to bind", "shown to bind activated", "to bind activated estrogen", "bind activated estrogen receptor", "activated estrogen receptor in", "estrogen receptor in the", "receptor in the nucleus", "in the nucleus and", "the nucleus and act", "nucleus and act as", "and act as its", "act as its transcriptional", "as its transcriptional co", "its transcriptional co factor", "transcriptional co factor in", "co factor in promoting", "factor in promoting transcription", "in promoting transcription of", "promoting transcription of some", "transcription of some estrogen", "of some estrogen regulated", "some estrogen regulated genes", "regulated genes such", "genes such as", "such as progesterone receptor", "as progesterone receptor gene", "progesterone receptor gene nr3c3", "receptor gene nr3c3 and", "gene nr3c3 and cxcl12", "nr3c3 and cxcl12 i.e.", "and cxcl12 i.e. sdf1", "i.e. sdf1 zhu", "sdf1 zhu et", "zhu et al. 2006", "al. 2006 . erbb4s80", "2006 . erbb4s80 may", ". erbb4s80 may inhibit", "erbb4s80 may inhibit transcription", "may inhibit transcription of", "inhibit transcription of telomerase", "transcription of telomerase reverse", "of telomerase reverse transcriptase", "reverse transcriptase tert", "tert by increasing", "by increasing methylation of", "increasing methylation of the", "methylation of the tert", "of the tert gene", "the tert gene promoter", "tert gene promoter through", "gene promoter through an", "promoter through an unknown", "through an unknown mechanism", "unknown mechanism ishibashi", "mechanism ishibashi et", "ishibashi et al. 2012", "et al. 2012 .

the", "al. 2012 .

the c", "2012 .

the c tail", ".

the c tail of", "c tail of erbb4", "tail of erbb4 possesses", "of erbb4 possesses several", "erbb4 possesses several ww", "possesses several ww domain", "several ww domain binding", "ww domain binding motifs", "binding motifs three", "motifs three in", "three in cyt1 isoform", "in cyt1 isoform and", "cyt1 isoform and two", "isoform and two in", "and two in cyt2", "two in cyt2 isoform", "isoform which", "which enable interaction of", "enable interaction of erbb4", "interaction of erbb4 with", "of erbb4 with ww", "erbb4 with ww domain", "with ww domain containing", "ww domain containing proteins.", "domain containing proteins. erbb4", "containing proteins. erbb4 s80", "erbb4 s80 through", "s80 through ww", "through ww domain binding", "binding motifs interacts", "motifs interacts with", "interacts with yap1 transcription", "with yap1 transcription factor", "transcription factor a", "factor a known", "a known proto oncogene", "proto oncogene and", "oncogene and may", "and may be a", "may be a co", "be a co regulator", "a co regulator of", "co regulator of yap1", "regulator of yap1 mediated", "of yap1 mediated transcription", "mediated transcription komuro", "transcription komuro et", "komuro et al. 2003", "al. 2003 omerovic", "2003 omerovic et", "omerovic et al. 2004", "et al. 2004 .", "al. 2004 . the", "2004 . the tumor", ". the tumor suppressor", "the tumor suppressor wwox", "suppressor wwox another", "wwox another ww", "another ww domain containing", "ww domain containing protein", "containing protein competes", "protein competes with", "competes with yap1 in", "with yap1 in binding", "yap1 in binding to", "in binding to erbb4", "binding to erbb4 s80", "to erbb4 s80 and", "erbb4 s80 and prevents", "s80 and prevents translocation", "and prevents translocation of", "prevents translocation of erbb4", "translocation of erbb4 s80", "of erbb4 s80 to", "erbb4 s80 to the", "s80 to the nucleus", "the nucleus aqeilan", "nucleus aqeilan et", "aqeilan et al. 2005", "et al. 2005 .", "al. 2005 . erbb4", "2005 . erbb4 s80", "erbb4 s80 is also", "s80 is also able", "is also able to", "also able to translocate", "translocate to the mitochondrial", "to the mitochondrial matrix", "mitochondrial matrix presumably", "matrix presumably when", "presumably when its nuclear", "when its nuclear translocation", "its nuclear translocation is", "nuclear translocation is inhibited.", "translocation is inhibited. once", "is inhibited. once in", "inhibited. once in the", "once in the mitochondrion", "the mitochondrion the", "mitochondrion the bh3", "the bh3 domain of", "bh3 domain of erbb4", "of erbb4 characteristic", "erbb4 characteristic of", "characteristic of bcl2 family", "of bcl2 family members", "family members may", "members may enable", "may enable it to", "enable it to act", "it to act as", "to act as a", "act as a pro", "as a pro apoptotic", "a pro apoptotic factor", "apoptotic factor naresh", "factor naresh et", "naresh et al. 2006", "besides signaling as a transmembrane", "signaling as a transmembrane receptor", "a transmembrane receptor ligand", "transmembrane receptor ligand activated", "receptor ligand activated homodimers", "ligand activated homodimers of erbb4", "activated homodimers of erbb4 jm", "homodimers of erbb4 jm a", "of erbb4 jm a isoforms", "jm a isoforms erbb4", "a isoforms erbb4 jm", "isoforms erbb4 jm a", "erbb4 jm a cyt1 and", "jm a cyt1 and erbb4", "a cyt1 and erbb4 jm", "cyt1 and erbb4 jm a", "and erbb4 jm a cyt2", "jm a cyt2 undergo", "a cyt2 undergo proteolytic", "cyt2 undergo proteolytic cleavage", "undergo proteolytic cleavage by adam17", "cleavage by adam17 tace", "adam17 tace in", "tace in the juxtamembrane", "the juxtamembrane region resulting", "juxtamembrane region resulting in", "region resulting in shedding", "resulting in shedding of the", "in shedding of the extracellular", "shedding of the extracellular domain", "of the extracellular domain and", "the extracellular domain and formation", "extracellular domain and formation of", "domain and formation of an", "and formation of an 80", "formation of an 80 kda", "of an 80 kda membrane", "an 80 kda membrane bound", "80 kda membrane bound erbb4", "kda membrane bound erbb4 fragment", "membrane bound erbb4 fragment known", "bound erbb4 fragment known as", "erbb4 fragment known as erbb4", "fragment known as erbb4 m80", "as erbb4 m80 rio", "erbb4 m80 rio et", "m80 rio et al.", "et al. 2000 cheng", "al. 2000 cheng et", "2000 cheng et al.", "cheng et al. 2003 .", "et al. 2003 . erbb4", "al. 2003 . erbb4 m80", "2003 . erbb4 m80 undergoes", ". erbb4 m80 undergoes further", "erbb4 m80 undergoes further proteolytic", "m80 undergoes further proteolytic cleavage", "further proteolytic cleavage mediated", "proteolytic cleavage mediated by", "cleavage mediated by the", "mediated by the gamma secretase", "by the gamma secretase complex", "gamma secretase complex which", "secretase complex which releases", "complex which releases the", "which releases the soluble 80", "releases the soluble 80 kda", "the soluble 80 kda erbb4", "soluble 80 kda erbb4 intracellular", "80 kda erbb4 intracellular domain", "erbb4 intracellular domain known", "intracellular domain known as", "domain known as erbb4", "known as erbb4 s80 or", "as erbb4 s80 or e4icd", "s80 or e4icd into", "or e4icd into the", "e4icd into the cytosol", "into the cytosol ni", "the cytosol ni et", "cytosol ni et al.", "ni et al. 2001 .", "et al. 2001 . erbb4", "al. 2001 . erbb4 s80", "2001 . erbb4 s80 is", ". erbb4 s80 is able", "erbb4 s80 is able to", "s80 is able to translocate", "is able to translocate to", "able to translocate to the", "to translocate to the nucleus", "to the nucleus promote", "the nucleus promote nuclear", "nucleus promote nuclear translocation", "promote nuclear translocation of various", "nuclear translocation of various transcription", "translocation of various transcription factors", "various transcription factors and", "transcription factors and act", "factors and act as", "and act as a transcription", "act as a transcription co", "as a transcription co factor.", "a transcription co factor. in", "transcription co factor. in neuronal", "co factor. in neuronal precursors", "in neuronal precursors erbb4", "neuronal precursors erbb4 s80", "precursors erbb4 s80 binds", "erbb4 s80 binds the complex", "s80 binds the complex of", "binds the complex of tab", "the complex of tab and", "complex of tab and ncor1", "tab and ncor1 helps", "and ncor1 helps to", "ncor1 helps to move", "helps to move the complex", "to move the complex into", "move the complex into the", "the complex into the nucleus", "into the nucleus and", "the nucleus and is", "nucleus and is a", "and is a co factor", "is a co factor of", "a co factor of tab:ncor1", "co factor of tab:ncor1 mediated", "factor of tab:ncor1 mediated inhibition", "of tab:ncor1 mediated inhibition of", "tab:ncor1 mediated inhibition of expression", "mediated inhibition of expression of", "inhibition of expression of astrocyte", "of expression of astrocyte differentiation", "expression of astrocyte differentiation genes", "of astrocyte differentiation genes gfap", "astrocyte differentiation genes gfap and", "differentiation genes gfap and s100b", "gfap and s100b sardi", "and s100b sardi et", "s100b sardi et al.", "sardi et al. 2006 .", "et al. 2006 . in", "al. 2006 . in mammary", "2006 . in mammary cells", "in mammary cells erbb4", "mammary cells erbb4 s80", "cells erbb4 s80 recruits", "erbb4 s80 recruits stat5a transcription", "s80 recruits stat5a transcription factor", "recruits stat5a transcription factor in", "stat5a transcription factor in the", "transcription factor in the cytosol", "in the cytosol shuttles", "the cytosol shuttles it", "cytosol shuttles it to", "shuttles it to the nucleus", "to the nucleus and", "the nucleus and acts", "nucleus and acts as", "and acts as the stat5a", "acts as the stat5a co", "as the stat5a co factor", "the stat5a co factor in", "stat5a co factor in binding", "co factor in binding to", "factor in binding to and", "in binding to and promoting", "binding to and promoting transcription", "to and promoting transcription from", "and promoting transcription from the", "promoting transcription from the beta", "transcription from the beta casein", "the beta casein csn2", "casein csn2 promoter", "csn2 promoter and", "promoter and may be", "and may be involved in", "may be involved in the", "be involved in the regulation", "involved in the regulation of", "in the regulation of other", "the regulation of other lactation", "regulation of other lactation related", "of other lactation related genes", "lactation related genes williams", "related genes williams et", "genes williams et al.", "et al. 2004 muraoka", "al. 2004 muraoka cook", "2004 muraoka cook et", "muraoka cook et al. 2008", "cook et al. 2008 .", "et al. 2008 . erbb4", "al. 2008 . erbb4 s80", "2008 . erbb4 s80 was", ". erbb4 s80 was also", "erbb4 s80 was also shown", "s80 was also shown to", "was also shown to bind", "also shown to bind activated", "shown to bind activated estrogen", "to bind activated estrogen receptor", "bind activated estrogen receptor in", "activated estrogen receptor in the", "estrogen receptor in the nucleus", "receptor in the nucleus and", "in the nucleus and act", "the nucleus and act as", "nucleus and act as its", "and act as its transcriptional", "act as its transcriptional co", "as its transcriptional co factor", "its transcriptional co factor in", "transcriptional co factor in promoting", "co factor in promoting transcription", "factor in promoting transcription of", "in promoting transcription of some", "promoting transcription of some estrogen", "transcription of some estrogen regulated", "of some estrogen regulated genes", "estrogen regulated genes such", "regulated genes such as", "genes such as progesterone", "such as progesterone receptor gene", "as progesterone receptor gene nr3c3", "progesterone receptor gene nr3c3 and", "receptor gene nr3c3 and cxcl12", "gene nr3c3 and cxcl12 i.e.", "nr3c3 and cxcl12 i.e. sdf1", "cxcl12 i.e. sdf1 zhu", "i.e. sdf1 zhu et", "sdf1 zhu et al.", "zhu et al. 2006 .", "et al. 2006 . erbb4s80", "al. 2006 . erbb4s80 may", "2006 . erbb4s80 may inhibit", ". erbb4s80 may inhibit transcription", "erbb4s80 may inhibit transcription of", "may inhibit transcription of telomerase", "inhibit transcription of telomerase reverse", "transcription of telomerase reverse transcriptase", "telomerase reverse transcriptase tert", "transcriptase tert by", "tert by increasing methylation", "by increasing methylation of the", "increasing methylation of the tert", "methylation of the tert gene", "of the tert gene promoter", "the tert gene promoter through", "tert gene promoter through an", "gene promoter through an unknown", "promoter through an unknown mechanism", "an unknown mechanism ishibashi", "unknown mechanism ishibashi et", "mechanism ishibashi et al.", "ishibashi et al. 2012 .

the", "et al. 2012 .

the c", "al. 2012 .

the c tail", "2012 .

the c tail of", ".

the c tail of erbb4", "c tail of erbb4 possesses", "tail of erbb4 possesses several", "of erbb4 possesses several ww", "erbb4 possesses several ww domain", "possesses several ww domain binding", "several ww domain binding motifs", "domain binding motifs three", "binding motifs three in", "motifs three in cyt1", "three in cyt1 isoform and", "in cyt1 isoform and two", "cyt1 isoform and two in", "isoform and two in cyt2", "and two in cyt2 isoform", "cyt2 isoform which", "isoform which enable", "which enable interaction of erbb4", "enable interaction of erbb4 with", "interaction of erbb4 with ww", "of erbb4 with ww domain", "erbb4 with ww domain containing", "with ww domain containing proteins.", "ww domain containing proteins. erbb4", "domain containing proteins. erbb4 s80", "proteins. erbb4 s80 through", "erbb4 s80 through ww", "s80 through ww domain", "through ww domain binding motifs", "domain binding motifs interacts", "binding motifs interacts with", "motifs interacts with yap1", "interacts with yap1 transcription factor", "yap1 transcription factor a", "transcription factor a known", "factor a known proto", "known proto oncogene and", "proto oncogene and may", "oncogene and may be", "and may be a co", "may be a co regulator", "be a co regulator of", "a co regulator of yap1", "co regulator of yap1 mediated", "regulator of yap1 mediated transcription", "yap1 mediated transcription komuro", "mediated transcription komuro et", "transcription komuro et al.", "et al. 2003 omerovic", "al. 2003 omerovic et", "2003 omerovic et al.", "omerovic et al. 2004 .", "et al. 2004 . the", "al. 2004 . the tumor", "2004 . the tumor suppressor", ". the tumor suppressor wwox", "tumor suppressor wwox another", "suppressor wwox another ww", "wwox another ww domain", "another ww domain containing protein", "domain containing protein competes", "containing protein competes with", "protein competes with yap1", "competes with yap1 in binding", "with yap1 in binding to", "yap1 in binding to erbb4", "in binding to erbb4 s80", "binding to erbb4 s80 and", "to erbb4 s80 and prevents", "erbb4 s80 and prevents translocation", "s80 and prevents translocation of", "and prevents translocation of erbb4", "prevents translocation of erbb4 s80", "translocation of erbb4 s80 to", "of erbb4 s80 to the", "erbb4 s80 to the nucleus", "to the nucleus aqeilan", "the nucleus aqeilan et", "nucleus aqeilan et al.", "aqeilan et al. 2005 .", "et al. 2005 . erbb4", "al. 2005 . erbb4 s80", "2005 . erbb4 s80 is", ". erbb4 s80 is also", "erbb4 s80 is also able", "s80 is also able to", "is also able to translocate", "also able to translocate to", "to translocate to the mitochondrial", "translocate to the mitochondrial matrix", "the mitochondrial matrix presumably", "mitochondrial matrix presumably when", "matrix presumably when its", "presumably when its nuclear translocation", "when its nuclear translocation is", "its nuclear translocation is inhibited.", "nuclear translocation is inhibited. once", "translocation is inhibited. once in", "is inhibited. once in the", "inhibited. once in the mitochondrion", "in the mitochondrion the", "the mitochondrion the bh3", "mitochondrion the bh3 domain", "the bh3 domain of erbb4", "domain of erbb4 characteristic", "of erbb4 characteristic of", "erbb4 characteristic of bcl2", "characteristic of bcl2 family members", "bcl2 family members may", "family members may enable", "members may enable it", "may enable it to act", "enable it to act as", "it to act as a", "to act as a pro", "act as a pro apoptotic", "as a pro apoptotic factor", "pro apoptotic factor naresh", "apoptotic factor naresh et", "factor naresh et al.", "naresh et al. 2006 ." ] }, { "record_id": "GLY_000594_1_37", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1257604", "r hsa", "hsa 1257604", "r hsa 1257604" ] }, { "record_id": "GLY_000594_1_37", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pip3 activates", "activates akt", "akt signaling", "pip3 activates akt", "activates akt signaling", "pip3 activates akt signaling", "signaling by", "by akt", "akt is", "is one", "one of", "of the", "the key", "key outcomes", "outcomes of", "of receptor", "receptor tyrosine", "tyrosine kinase", "activation. akt", "is activated", "activated by", "by the", "the cellular", "cellular second", "second messenger", "messenger pip3", "a phospholipid", "phospholipid that", "that is", "is generated", "generated by", "by pi3k.", "pi3k. in", "in ustimulated", "ustimulated cells", "pi3k class", "class ia", "ia enzymes", "enzymes reside", "reside in", "in the", "the cytosol", "cytosol as", "as inactive", "inactive heterodimers", "heterodimers composed", "composed of", "of p85", "p85 regulatory", "regulatory subunit", "subunit and", "and p110", "p110 catalytic", "catalytic subunit.", "subunit. in", "in this", "this complex", "p85 stabilizes", "stabilizes p110", "p110 while", "while inhibiting", "inhibiting its", "its catalytic", "catalytic activity.", "activity. upon", "upon binding", "binding of", "of extracellular", "extracellular ligands", "ligands to", "to rtks", "receptors dimerize", "dimerize and", "and undergo", "undergo autophosphorylation.", "autophosphorylation. the", "the regulatory", "subunit of", "of pi3k", "is recruited", "recruited to", "to phosphorylated", "phosphorylated cytosolic", "cytosolic rtk", "rtk domains", "domains either", "either directly", "directly or", "or indirectly", "through adaptor", "adaptor proteins", "leading to", "to a", "a conformational", "conformational change", "change in", "the pi3k", "pi3k ia", "ia heterodimer", "heterodimer that", "that relieves", "relieves inhibition", "inhibition of", "the p110", "subunit. activated", "activated pi3k", "ia phosphorylates", "phosphorylates pip2", "converting it", "it to", "to pip3", "this reaction", "reaction is", "is negatively", "negatively regulated", "regulated by", "by pten", "pten phosphatase.", "phosphatase. pip3", "pip3 recruits", "recruits akt", "akt to", "to the", "the plasma", "plasma membrane", "allowing torc2", "torc2 to", "to phosphorylate", "phosphorylate a", "a conserved", "conserved serine", "serine residue", "residue of", "of akt.", "akt. phosphorylation", "phosphorylation of", "of this", "this serine", "serine induces", "induces a", "a conformation", "conformation change", "in akt", "exposing a", "conserved threonine", "threonine residue", "residue that", "is then", "then phosphorylated", "phosphorylated by", "by pdpk1", "pdk1 .", ". phosphorylation", "of both", "both the", "the threonine", "threonine and", "and the", "the serine", "residue is", "is required", "required to", "to fully", "fully activate", "activate akt.", "akt. the", "the active", "active akt", "akt then", "then dissociates", "dissociates from", "from pip3", "pip3 and", "and phosphorylates", "phosphorylates a", "a number", "number of", "of cytosolic", "cytosolic and", "and nuclear", "nuclear proteins", "proteins that", "that play", "play important", "important roles", "roles in", "in cell", "cell survival", "survival and", "and metabolism.", "metabolism. for", "for a", "a recent", "recent review", "review of", "of akt", "please refer", "refer to", "to manning", "manning and", "and cantley", "signaling by akt", "by akt is", "akt is one", "is one of", "one of the", "of the key", "the key outcomes", "key outcomes of", "outcomes of receptor", "of receptor tyrosine", "receptor tyrosine kinase", "kinase rtk", "rtk activation.", "activation. akt is", "akt is activated", "is activated by", "activated by the", "by the cellular", "the cellular second", "cellular second messenger", "second messenger pip3", "pip3 a", "a phospholipid that", "phospholipid that is", "that is generated", "is generated by", "generated by pi3k.", "by pi3k. in", "pi3k. in ustimulated", "in ustimulated cells", "cells pi3k", "pi3k class ia", "class ia enzymes", "ia enzymes reside", "enzymes reside in", "reside in the", "in the cytosol", "the cytosol as", "cytosol as inactive", "as inactive heterodimers", "inactive heterodimers composed", "heterodimers composed of", "composed of p85", "of p85 regulatory", "p85 regulatory subunit", "regulatory subunit and", "subunit and p110", "and p110 catalytic", "p110 catalytic subunit.", "catalytic subunit. in", "subunit. in this", "in this complex", "complex p85", "p85 stabilizes p110", "stabilizes p110 while", "p110 while inhibiting", "while inhibiting its", "inhibiting its catalytic", "its catalytic activity.", "catalytic activity. upon", "activity. upon binding", "upon binding of", "binding of extracellular", "of extracellular ligands", "extracellular ligands to", "ligands to rtks", "rtks receptors", "receptors dimerize and", "dimerize and undergo", "and undergo autophosphorylation.", "undergo autophosphorylation. the", "autophosphorylation. the regulatory", "the regulatory subunit", "regulatory subunit of", "subunit of pi3k", "pi3k p85", "p85 is", "is recruited to", "recruited to phosphorylated", "to phosphorylated cytosolic", "phosphorylated cytosolic rtk", "cytosolic rtk domains", "rtk domains either", "domains either directly", "either directly or", "directly or indirectly", "indirectly through", "through adaptor proteins", "proteins leading", "leading to a", "to a conformational", "a conformational change", "conformational change in", "change in the", "in the pi3k", "the pi3k ia", "pi3k ia heterodimer", "ia heterodimer that", "heterodimer that relieves", "that relieves inhibition", "relieves inhibition of", "inhibition of the", "of the p110", "the p110 catalytic", "catalytic subunit. activated", "subunit. activated pi3k", "activated pi3k ia", "pi3k ia phosphorylates", "ia phosphorylates pip2", "pip2 converting", "converting it to", "it to pip3", "pip3 this", "this reaction is", "reaction is negatively", "is negatively regulated", "negatively regulated by", "regulated by pten", "by pten phosphatase.", "pten phosphatase. pip3", "phosphatase. pip3 recruits", "pip3 recruits akt", "recruits akt to", "akt to the", "to the plasma", "the plasma membrane", "membrane allowing", "allowing torc2 to", "torc2 to phosphorylate", "to phosphorylate a", "phosphorylate a conserved", "a conserved serine", "conserved serine residue", "serine residue of", "residue of akt.", "of akt. phosphorylation", "akt. phosphorylation of", "phosphorylation of this", "of this serine", "this serine induces", "serine induces a", "induces a conformation", "a conformation change", "conformation change in", "change in akt", "akt exposing", "exposing a conserved", "a conserved threonine", "conserved threonine residue", "threonine residue that", "residue that is", "that is then", "is then phosphorylated", "then phosphorylated by", "phosphorylated by pdpk1", "pdpk1 pdk1", "pdk1 . phosphorylation", ". phosphorylation of", "phosphorylation of both", "of both the", "both the threonine", "the threonine and", "threonine and the", "and the serine", "the serine residue", "serine residue is", "residue is required", "is required to", "required to fully", "to fully activate", "fully activate akt.", "activate akt. the", "akt. the active", "the active akt", "active akt then", "akt then dissociates", "then dissociates from", "dissociates from pip3", "from pip3 and", "pip3 and phosphorylates", "and phosphorylates a", "phosphorylates a number", "a number of", "number of cytosolic", "of cytosolic and", "cytosolic and nuclear", "and nuclear proteins", "nuclear proteins that", "proteins that play", "that play important", "play important roles", "important roles in", "roles in cell", "in cell survival", "cell survival and", "survival and metabolism.", "and metabolism. for", "metabolism. for a", "for a recent", "a recent review", "recent review of", "review of akt", "of akt signaling", "signaling please", "please refer to", "refer to manning", "to manning and", "manning and cantley", "cantley 2007.", "signaling by akt is", "by akt is one", "akt is one of", "is one of the", "one of the key", "of the key outcomes", "the key outcomes of", "key outcomes of receptor", "outcomes of receptor tyrosine", "of receptor tyrosine kinase", "tyrosine kinase rtk", "rtk activation. akt", "activation. akt is activated", "akt is activated by", "is activated by the", "activated by the cellular", "by the cellular second", "the cellular second messenger", "cellular second messenger pip3", "messenger pip3 a", "pip3 a phospholipid", "a phospholipid that is", "phospholipid that is generated", "that is generated by", "is generated by pi3k.", "generated by pi3k. in", "by pi3k. in ustimulated", "pi3k. in ustimulated cells", "ustimulated cells pi3k", "cells pi3k class", "pi3k class ia enzymes", "class ia enzymes reside", "ia enzymes reside in", "enzymes reside in the", "reside in the cytosol", "in the cytosol as", "the cytosol as inactive", "cytosol as inactive heterodimers", "as inactive heterodimers composed", "inactive heterodimers composed of", "heterodimers composed of p85", "composed of p85 regulatory", "of p85 regulatory subunit", "p85 regulatory subunit and", "regulatory subunit and p110", "subunit and p110 catalytic", "and p110 catalytic subunit.", "p110 catalytic subunit. in", "catalytic subunit. in this", "subunit. in this complex", "this complex p85", "complex p85 stabilizes", "p85 stabilizes p110 while", "stabilizes p110 while inhibiting", "p110 while inhibiting its", "while inhibiting its catalytic", "inhibiting its catalytic activity.", "its catalytic activity. upon", "catalytic activity. upon binding", "activity. upon binding of", "upon binding of extracellular", "binding of extracellular ligands", "of extracellular ligands to", "extracellular ligands to rtks", "to rtks receptors", "rtks receptors dimerize", "receptors dimerize and undergo", "dimerize and undergo autophosphorylation.", "and undergo autophosphorylation. the", "undergo autophosphorylation. the regulatory", "autophosphorylation. the regulatory subunit", "the regulatory subunit of", "regulatory subunit of pi3k", "of pi3k p85", "p85 is recruited", "is recruited to phosphorylated", "recruited to phosphorylated cytosolic", "to phosphorylated cytosolic rtk", "phosphorylated cytosolic rtk domains", "cytosolic rtk domains either", "rtk domains either directly", "domains either directly or", "either directly or indirectly", "or indirectly through", "indirectly through adaptor", "adaptor proteins leading", "proteins leading to", "leading to a conformational", "to a conformational change", "a conformational change in", "conformational change in the", "change in the pi3k", "in the pi3k ia", "the pi3k ia heterodimer", "pi3k ia heterodimer that", "ia heterodimer that relieves", "heterodimer that relieves inhibition", "that relieves inhibition of", "relieves inhibition of the", "inhibition of the p110", "of the p110 catalytic", "the p110 catalytic subunit.", "p110 catalytic subunit. activated", "catalytic subunit. activated pi3k", "subunit. activated pi3k ia", "activated pi3k ia phosphorylates", "pi3k ia phosphorylates pip2", "phosphorylates pip2 converting", "pip2 converting it", "converting it to pip3", "to pip3 this", "pip3 this reaction", "this reaction is negatively", "reaction is negatively regulated", "is negatively regulated by", "negatively regulated by pten", "regulated by pten phosphatase.", "by pten phosphatase. pip3", "pten phosphatase. pip3 recruits", "phosphatase. pip3 recruits akt", "pip3 recruits akt to", "recruits akt to the", "akt to the plasma", "to the plasma membrane", "plasma membrane allowing", "membrane allowing torc2", "allowing torc2 to phosphorylate", "torc2 to phosphorylate a", "to phosphorylate a conserved", "phosphorylate a conserved serine", "a conserved serine residue", "conserved serine residue of", "serine residue of akt.", "residue of akt. phosphorylation", "of akt. phosphorylation of", "akt. phosphorylation of this", "phosphorylation of this serine", "of this serine 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dissociates from", "then dissociates from pip3", "dissociates from pip3 and", "from pip3 and phosphorylates", "pip3 and phosphorylates a", "and phosphorylates a number", "phosphorylates a number of", "a number of cytosolic", "number of cytosolic and", "of cytosolic and nuclear", "cytosolic and nuclear proteins", "and nuclear proteins that", "nuclear proteins that play", "proteins that play important", "that play important roles", "play important roles in", "important roles in cell", "roles in cell survival", "in cell survival and", "cell survival and metabolism.", "survival and metabolism. for", "and metabolism. for a", "metabolism. for a recent", "for a recent review", "a recent review of", "recent review of akt", "review of akt signaling", "akt signaling please", "signaling please refer", "please refer to manning", "refer to manning and", "to manning and cantley", "and cantley 2007.", "signaling by akt is one", "by akt is one of", "akt is one of the", "is one of the key", "one of the key outcomes", "of the key outcomes of", "the key outcomes of receptor", "key outcomes of receptor tyrosine", "outcomes of receptor tyrosine kinase", "receptor tyrosine kinase rtk", "kinase rtk activation.", "rtk activation. akt is", "activation. akt is activated by", "akt is activated by the", "is activated by the cellular", "activated by the cellular second", "by the cellular second messenger", "the cellular second messenger pip3", "second messenger pip3 a", "messenger pip3 a phospholipid", "pip3 a phospholipid that", "a phospholipid that is generated", "phospholipid that is generated by", "that is generated by pi3k.", "is generated by pi3k. in", "generated by pi3k. in ustimulated", "by pi3k. in ustimulated cells", "in ustimulated cells pi3k", "ustimulated cells pi3k class", "cells pi3k class ia", "pi3k class ia enzymes reside", "class ia enzymes reside in", "ia enzymes reside in the", "enzymes reside in the cytosol", "reside in the cytosol as", "in the cytosol as inactive", "the cytosol as inactive heterodimers", "cytosol as inactive heterodimers composed", "as inactive heterodimers composed of", "inactive heterodimers composed of p85", "heterodimers composed of p85 regulatory", "composed of p85 regulatory subunit", "of p85 regulatory subunit and", "p85 regulatory subunit and p110", "regulatory subunit and p110 catalytic", "subunit and p110 catalytic subunit.", "and p110 catalytic subunit. in", "p110 catalytic subunit. in this", "catalytic subunit. in this complex", "in this complex p85", "this complex p85 stabilizes", "complex p85 stabilizes p110", "p85 stabilizes p110 while inhibiting", "stabilizes p110 while inhibiting its", "p110 while inhibiting its catalytic", "while inhibiting its catalytic activity.", "inhibiting its catalytic activity. upon", "its catalytic activity. upon binding", "catalytic activity. upon binding of", "activity. upon binding of extracellular", "upon binding of extracellular ligands", "binding of extracellular ligands to", "of extracellular ligands to rtks", "ligands to rtks receptors", "to rtks receptors dimerize", "rtks receptors dimerize and", "receptors dimerize and undergo autophosphorylation.", "dimerize and undergo autophosphorylation. the", "and undergo autophosphorylation. the regulatory", "undergo autophosphorylation. the regulatory subunit", "autophosphorylation. the regulatory subunit of", "the regulatory subunit of pi3k", "subunit of pi3k p85", "pi3k p85 is", "p85 is recruited to", "is recruited to phosphorylated cytosolic", "recruited to phosphorylated cytosolic rtk", "to phosphorylated cytosolic rtk domains", "phosphorylated cytosolic rtk domains either", "cytosolic rtk domains either directly", "rtk domains either directly or", "domains either directly or indirectly", "directly or indirectly through", "or indirectly through adaptor", "indirectly through adaptor proteins", "through adaptor proteins leading", "adaptor proteins leading to", "proteins leading to a", "leading to a conformational change", "to a conformational change in", "a conformational change in the", "conformational change in the pi3k", "change in the pi3k ia", "in the pi3k ia heterodimer", "the pi3k ia heterodimer that", "pi3k ia heterodimer that relieves", "ia heterodimer that relieves inhibition", "heterodimer that relieves inhibition of", "that relieves inhibition of the", "relieves inhibition of the p110", "inhibition of the p110 catalytic", "of the p110 catalytic subunit.", "the p110 catalytic subunit. activated", "p110 catalytic subunit. activated pi3k", "catalytic subunit. activated pi3k ia", "subunit. activated pi3k ia phosphorylates", "activated pi3k ia phosphorylates pip2", "ia phosphorylates pip2 converting", "phosphorylates pip2 converting it", "pip2 converting it to", "it to pip3 this", "to pip3 this reaction", "pip3 this reaction is", "this reaction is negatively regulated", "reaction is negatively regulated by", "is negatively regulated by pten", "negatively regulated by pten phosphatase.", "regulated by pten phosphatase. pip3", "by pten phosphatase. pip3 recruits", "pten phosphatase. pip3 recruits akt", "phosphatase. pip3 recruits akt to", "pip3 recruits akt to the", "recruits akt to the plasma", "akt to the plasma membrane", "the plasma membrane allowing", "plasma membrane allowing torc2", "membrane allowing torc2 to", "allowing torc2 to phosphorylate a", "torc2 to phosphorylate a conserved", "to phosphorylate a conserved serine", "phosphorylate a conserved serine residue", "a conserved serine residue of", "conserved serine residue of akt.", "serine residue of akt. phosphorylation", "residue of akt. phosphorylation of", "of akt. phosphorylation of this", "akt. phosphorylation of this serine", "phosphorylation of this serine induces", "of this serine induces a", "this serine induces a conformation", "serine induces a conformation change", "induces a conformation change in", "a conformation change in akt", "change in akt exposing", "in akt exposing a", "akt exposing a conserved", "exposing a conserved threonine residue", "a conserved threonine residue that", "conserved threonine residue that is", "threonine residue that is then", "residue that is then phosphorylated", "that is then phosphorylated by", "is then phosphorylated by pdpk1", "phosphorylated by pdpk1 pdk1", "by pdpk1 pdk1 .", "pdpk1 pdk1 . phosphorylation", "pdk1 . phosphorylation of both", ". phosphorylation of both the", "phosphorylation of both the threonine", "of both the threonine and", "both the threonine and the", "the threonine and the serine", "threonine and the serine residue", "and the serine residue is", "the serine residue is required", "serine residue is required to", "residue is required to fully", "is required to fully activate", "required to fully activate akt.", "to fully activate akt. the", "fully activate akt. the active", "activate akt. the active akt", "akt. the active akt then", "the active akt then dissociates", "active akt then dissociates from", "akt then dissociates from pip3", "then dissociates from pip3 and", "dissociates from pip3 and phosphorylates", "from pip3 and phosphorylates a", "pip3 and phosphorylates a number", "and phosphorylates a number of", "phosphorylates a number of cytosolic", "a number of cytosolic and", "number of cytosolic and nuclear", "of cytosolic and nuclear proteins", "cytosolic and nuclear proteins that", "and nuclear proteins that play", "nuclear proteins that play important", "proteins that play important roles", "that play important roles in", "play important roles in cell", "important roles in cell survival", "roles in cell survival and", "in cell survival and metabolism.", "cell survival and metabolism. for", "survival and metabolism. for a", "and metabolism. for a recent", "metabolism. for a recent review", "for a recent review of", "a recent review of akt", "recent review of akt signaling", "of akt signaling please", "akt signaling please refer", "signaling please refer to", "please refer to manning and", "refer to manning and cantley", "manning and cantley 2007." ] }, { "record_id": "GLY_000594_1_38", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1266695", "r hsa", "hsa 1266695", "r hsa 1266695" ] }, { "record_id": "GLY_000594_1_38", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 7", "7 signaling", "interleukin 7 signaling", "is produced", "produced primarily", "primarily by", "by t", "t zone", "zone fibroblastic", "fibroblastic reticular", "reticular cells", "cells found", "found in", "in lymphoid", "lymphoid organs", "and also", "also expressed", "expressed by", "by non", "non hematopoietic", "hematopoietic stromal", "stromal cells", "cells present", "present in", "in other", "other tissues", "tissues including", "including the", "the skin", "intestine and", "and liver.", "liver. it", "it is", "is an", "an essential", "essential survival", "survival factor", "factor for", "for lymphocytes", "playing a", "a key", "key anti", "anti apoptotic", "apoptotic role", "role in", "in t", "t cell", "cell development", "as well", "well as", "as mediating", "mediating peripheral", "peripheral t", "cell maintenance", "maintenance and", "and proliferation.", "proliferation. this", "this dual", "dual function", "function is", "is reflected", "reflected in", "in a", "a dose", "dose response", "response relationship", "relationship that", "that distinguishes", "distinguishes the", "the survival", "survival function", "function from", "from the", "the proliferative", "proliferative activity", "low doses", "doses of", "of il7", "<1 ng/ml", "sustain only", "only survival", "higher doses", ">1 ng/ml", "promote survival", "survival and", "and cell", "cell cycling", "kittipatarin et", "et al.", "al. 2006", "swainson et", "al. 2007", "2007 .

the", ".

the il7", "il7 receptor", "receptor is", "is a", "a heterodimeric", "heterodimeric complex", "complex of", "of the", "the the", "the common", "common cytokine", "cytokine receptor", "receptor gamma", "gamma chain", "or gc", "and the", "the il7", "receptor alpha", "alpha chain", "cd127 .", ". both", "both chains", "chains are", "are members", "members of", "the type", "type 1", "1 cytokine", "cytokine family.", "family. neither", "neither chain", "chain is", "is unique", "unique to", "to the", "receptor as", "as il7r", "il7r is", "is utilized", "utilized by", "by the", "the receptor", "receptor for", "for thymic", "thymic stromal", "stromal lymphopoietin", "while il2rg", "il2rg is", "is shared", "shared with", "with the", "the receptors", "receptors for", "for il2", "il15 and", "and il21.", "il21. il2rg", "il2rg consists", "consists of", "of a", "a single", "single transmembrane", "transmembrane region", "region and", "and a", "a 240aa", "240aa extracellular", "extracellular region", "region that", "that includes", "includes a", "a fibronectin", "fibronectin type", "type iii", "domain thought", "thought to", "to be", "be involved", "involved in", "in receptor", "receptor complex", "complex formation.", "formation. it", "is expressed", "expressed on", "on most", "most lymphocyte", "lymphocyte populations.", "populations. null", "null mutations", "mutations of", "of il2rg", "il2rg in", "in humans", "humans cause", "cause x", "x linked", "linked severe", "severe combined", "combined immunodeficiency", "x scid", "which has", "has a", "a phenotype", "phenotype of", "severely reduced", "reduced t", "cell and", "and natural", "natural killer", "cell populations", "but normal", "normal numbers", "numbers of", "of b", "b cells.", "cells. in", "in addition", "addition to", "to reduced", "and nk", "nk cell", "cell numbers", "il2rg knockout", "knockout mice", "mice also", "also have", "have dramatically", "dramatically reduced", "reduced b", "b cell", "populations suggesting", "suggesting that", "that il2rg", "is more", "more critical", "critical for", "for b", "development in", "in mice", "mice than", "than in", "in humans.", "humans. patients", "patients with", "with severe", "phenotype due", "due to", "to il7r", "il7r mutations", "see puel", "puel &", "& leonard", "leonard 2000", "or a", "a partial", "partial deficiency", "deficiency of", "of il7r", "roifman et", "al. 2000", "have markedly", "markedly reduced", "reduced circulating", "circulating t", "t cells", "normal levels", "levels of", "of peripheral", "peripheral blood", "blood b", "b cells", "cells and", "nk cells", "similar to", "the phenotype", "il2rg mutations", "highlighting a", "a requirement", "requirement for", "for il7", "il7 in", "cell lymphopoiesis.", "lymphopoiesis. it", "it has", "has been", "been suggested", "suggested that", "that il7", "il7 is", "is essential", "essential for", "for murine", "but not", "not human", "human b", "but recent", "recent studies", "studies indicate", "indicate that", "for human", "cell production", "production from", "from adult", "adult bone", "bone marrow", "marrow and", "and that", "il7 induced", "induced expansion", "expansion of", "the progenitor", "progenitor b", "cell compartment", "compartment is", "is increasingly", "increasingly critical", "production during", "during later", "later stages", "stages of", "of development", "parrish et", "al. 2009", "2009 .

il7", ".

il7 has", "been shown", "shown to", "to induce", "induce rapid", "rapid and", "and dose", "dose dependent", "dependent tyrosine", "tyrosine phosphorylation", "phosphorylation of", "of jaks", "jaks 1", "1 and", "and 3", "and concomitantly", "concomitantly tyrosine", "phosphorylation and", "and dna", "dna binding", "binding activity", "activity of", "of stat5a/b", "foxwell et", "al. 1995", "1995 .", ". il7r", "il7r was", "was shown", "to directly", "directly induce", "induce the", "the activation", "activation of", "jaks and", "and stats", "stats by", "by van", "van der", "der plas", "plas et", "1996 .", ". jak1", "jak1 and", "and jak3", "jak3 knockout", "mice displayed", "displayed severely", "severely impaired", "impaired thymic", "thymic development", "further supporting", "supporting their", "their importance", "importance in", "in il7", "il7 signaling", "rodig et", "al. 1998", "nosaka et", "1995 .

the", ".

the role", "role of", "of stat5", "stat5 in", "signaling has", "been studied", "studied largely", "largely in", "in mouse", "mouse models.", "models. tyr449", "tyr449 in", "in the", "the cytoplasmic", "cytoplasmic domain", "domain of", "of il7ra", "il7ra is", "is required", "required for", "for t", "in vivo", "vivo and", "and activation", "of jak/stat5", "jak/stat5 and", "and pi3k/akt", "pi3k/akt pathways", "jiang et", "al. 2004", "pallard et", "al. 1999", "1999 .", ". t", "cells from", "from an", "an il7r", "il7r y449f", "y449f knock", "knock in", "mouse did", "did not", "not activate", "activate stat5", "osbourne et", "indicating that", "il7 regulates", "regulates stat5", "stat5 activity", "activity via", "via this", "this key", "key tyrosine", "tyrosine residue.", "residue. stat5", "stat5 seems", "seems to", "to enhance", "enhance proliferation", "proliferation of", "of multiple", "multiple cell", "cell lineages", "lineages in", "mouse models", "models but", "but it", "it remains", "remains unclear", "unclear whether", "whether stat5", "stat5 is", "required solely", "solely for", "for survival", "survival signaling", "signaling or", "or also", "also for", "for the", "the induction", "induction of", "of proliferative", "kittipatarin &", "& khaled", ".

the model", "model for", "receptor signaling", "signaling is", "is believed", "believed to", "to resemble", "resemble that", "that of", "of other", "other gc", "gc family", "family cytokines", "based on", "on detailed", "detailed studies", "studies of", "the il2", "il2 receptor", "where il2rb", "il2rb binds", "binds constitutively", "constitutively to", "to jak1", "jak1 while", "while jak3", "jak3 is", "is pre", "pre associated", "associated uniquely", "uniquely with", "the il2rg", "il2rg chain.", "chain. extending", "extending this", "this model", "model to", "to il7", "il7 suggests", "suggests a", "a similar", "similar series", "series of", "of events:", "events: il7r", "il7r constitutively", "constitutively associated", "associated with", "with jak1", "jak1 binds", "binds il7", "the resulting", "resulting trimer", "trimer recruits", "recruits il2rg:jak3", "bringing jak1", "jak3 into", "into proximity.", "proximity. the", "the association", "association of", "of both", "chains of", "receptor orients", "orients the", "cytoplasmic domains", "domains of", "receptor chains", "chains so", "so that", "that their", "their associated", "associated kinases", "janus and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 kinases", "can phosphorylate", "phosphorylate sequence", "sequence elements", "elements on", "on the", "al. 2005", "2005 .", ". jaks", "jaks have", "have low", "low intrinsic", "intrinsic enzymatic", "enzymatic activity", "but after", "after mutual", "mutual phosphorylation", "phosphorylation acquire", "acquire much", "much higher", "higher activity", "leading to", "to phosphorylation", "the critical", "critical y449", "y449 site", "site on", "on il7r.", "il7r. this", "this site", "site binds", "binds stat5", "stat5 and", "and possibly", "possibly other", "other signaling", "signaling adapters", "they in", "in turn", "turn become", "become phosphorylated", "phosphorylated by", "by jak1", "jak1 and/or", "and/or jak3.", "jak3. phosphorylated", "phosphorylated stats", "stats translocate", "translocate to", "the nucleus", "nucleus and", "and trigger", "trigger the", "the transcriptional", "transcriptional events", "events of", "of their", "their target", "target genes.

the", "genes.

the role", "the pi3k/akt", "pi3k/akt pathway", "pathway in", "is controversial.", "controversial. it", "a potential", "potential t", "cell survival", "survival pathway", "pathway because", "because in", "in many", "many cell", "cell types", "types pi3k", "pi3k signaling", "signaling regulates", "regulates diverse", "diverse cellular", "cellular functions", "functions such", "such as", "as cell", "cell cycle", "cycle progression", "and metabolism.", "metabolism. the", "the erk/mapk", "erk/mapk pathway", "pathway does", "does not", "not appear", "appear to", "crawley et", "al. 1996", "1996 .

it", ".

it is", "is not", "not clear", "clear how", "how il7", "il7 influences", "influences cell", "cell proliferation.", "proliferation. in", "the absence", "absence of", "a proliferative", "proliferative signal", "signal such", "as il7", "il7 or", "or il3", "dependent lymphocytes", "lymphocytes arrest", "arrest in", "the g0/g1", "g0/g1 phase", "phase of", "the cell", "cell cycle.", "cycle. to", "to exit", "exit this", "this phase", "cells typically", "typically activate", "activate specific", "specific g1", "g1 cyclin", "cyclin dependent", "dependent kinases/cyclins", "kinases/cyclins and", "and down", "down regulate", "regulate cell", "cycle inhibitors", "inhibitors such", "as cyclin", "dependent kinase", "kinase inhibitor", "inhibitor 1b", "cdkn1b or", "or p27kip1", "p27kip1 .", ". there", "there is", "is indirect", "indirect evidence", "evidence suggesting", "suggesting a", "a possible", "possible role", "role for", "il7 stimulated", "stimulated activation", "of pi3k/akt", "pi3k/akt signaling", "obtained from", "from transformed", "transformed cell", "cell lines", "lines and", "and thymocytes", "not confirmed", "confirmed by", "by observations", "observations using", "using primary", "primary t", "2007 .", ". il7", "il7 withdrawal", "withdrawal results", "results in", "in g1/s", "g1/s cell", "cycle arrest", "arrest and", "and is", "is correlated", "correlated with", "with loss", "loss of", "of cdk2", "cdk2 activity", "geiselhart et", "al. 2001", "both events", "events which", "which are", "are known", "known to", "be regulated", "regulated by", "the dephosphorylating", "dephosphorylating activity", "of cdc25a.", "cdc25a. expression", "expression of", "a p38", "p38 mapk", "mapk resistant", "resistant cdc25a", "cdc25a mutant", "mutant in", "in an", "an il", "il 7", "7 dependent", "dependent t", "cell line", "line as", "as in", "in peripheral", "cells was", "was sufficient", "sufficient to", "to sustain", "sustain cell", "and promote", "promote cell", "cycling for", "for several", "several days", "days in", "khaled et", ". cdkn1b", "cdkn1b is", "a member", "member of", "the cip/kip", "cip/kip family", "family of", "of cyclin", "dependent cell", "that negatively", "negatively regulates", "regulates the", "the g1/s", "g1/s transition.", "transition. in", "il7 dependent", "the expression", "of cdkn1b", "cdkn1b was", "to cause", "cause g1", "g1 arrest", "the presence", "presence of", "of il7.", "il7. withdrawal", "withdrawal of", "induced the", "the upregulation", "upregulation of", "cdkn1b and", "and arrested", "arrested cells", "cells in", "in g1", "g1 while", "while sirna", "sirna knockout", "knockout of", "cdkn1b enhanced", "enhanced cell", "cycle progression.", "progression. however", "adoptive transfer", "transfer of", "cdkn1b deficient", "deficient lymphocytes", "lymphocytes into", "into il7", "il7 deficient", "deficient mice", "mice indicated", "indicated that", "that loss", "cdkn1b could", "could only", "only partially", "partially compensate", "compensate for", "il7 signal", "signal needed", "needed by", "cells to", "to expand", "expand in", "a lymphopenic", "lymphopenic environment", "li et", "so though", "though cdkn1b", "cdkn1b may", "may be", "in negative", "negative regulation", "regulation of", "cycle through", "through an", "an effect", "effect on", "on cdk2", "its absence", "absence is", "not sufficient", "to fully", "fully induce", "induce cell", "cycling under", "under lymphopenic", "lymphopenic conditions.", "7 il7", "is produced primarily", "produced primarily by", "primarily by t", "by t zone", "t zone fibroblastic", "zone fibroblastic reticular", "fibroblastic reticular cells", "reticular cells found", "cells found in", "found in lymphoid", "in lymphoid organs", "organs and", "and also expressed", "also expressed by", "expressed by non", "by non hematopoietic", "non hematopoietic stromal", "hematopoietic stromal cells", "stromal cells present", "cells present in", "present in other", "in other tissues", "other tissues including", "tissues including the", "including the skin", "skin intestine", "intestine and liver.", "and liver. it", "liver. it is", "it is an", "is an essential", "an essential survival", "essential survival factor", "survival factor for", "factor for lymphocytes", "lymphocytes playing", "playing a key", "a key anti", "key anti apoptotic", "anti apoptotic role", "apoptotic role in", "role in t", "in t cell", "t cell development", "development as", "as well as", "well as mediating", "as mediating peripheral", "mediating peripheral t", "peripheral t cell", "t cell maintenance", "cell maintenance and", "maintenance and proliferation.", "and proliferation. this", "proliferation. this dual", "this dual function", "dual function is", "function is reflected", "is reflected in", "reflected in a", "in a dose", "a dose response", "dose response relationship", "response relationship that", "relationship that distinguishes", "that distinguishes the", "distinguishes the survival", "the survival function", "survival function from", "function from the", "from the proliferative", "the proliferative activity", "activity low", "low doses of", "doses of il7", "il7 <1", "ng/ml sustain", "sustain only survival", "survival higher", "ng/ml promote", "promote survival and", "survival and cell", "and cell cycling", "cycling kittipatarin", "kittipatarin et al.", "et al. 2006", "2006 swainson", "swainson et al.", "et al. 2007", "al. 2007 .

the", "2007 .

the il7", ".

the il7 receptor", "il7 receptor is", "receptor is a", "is a heterodimeric", "a heterodimeric complex", "heterodimeric complex of", "complex of the", "of the the", "the the common", "the common cytokine", "common cytokine receptor", "cytokine receptor gamma", "receptor gamma chain", "chain il2rg", "il2rg cd132", "cd132 or", "gc and", "and the il7", "the il7 receptor", "il7 receptor alpha", "receptor alpha chain", "chain il7r", "il7r il7ra", "il7ra cd127", "cd127 . both", ". both chains", "both chains are", "chains are members", "are members of", "members of the", "of the type", "the type 1", "type 1 cytokine", "1 cytokine family.", "cytokine family. neither", "family. neither chain", "neither chain is", "chain is unique", "is unique to", "unique to the", "to the il7", "il7 receptor as", "receptor as il7r", "as il7r is", "il7r is utilized", "is utilized by", "utilized by the", "by the receptor", "the receptor for", "receptor for thymic", "for thymic stromal", "thymic stromal lymphopoietin", "lymphopoietin tslp", "tslp while", "while il2rg is", "il2rg is shared", "is shared with", "shared with the", "with the receptors", "the receptors for", "receptors for il2", "il2 il4", "il4 il9", "il9 il15", "il15 and il21.", "and il21. il2rg", "il21. il2rg consists", "il2rg consists of", "consists of a", "of a single", "a single transmembrane", "single transmembrane region", "transmembrane region and", "region and a", "and a 240aa", "a 240aa extracellular", "240aa extracellular region", "extracellular region that", "region that includes", "that includes a", "includes a fibronectin", "a fibronectin type", "fibronectin type iii", "iii fniii", "fniii domain", "domain thought to", "thought to be", "to be involved", "be involved in", "involved in receptor", "in receptor complex", "receptor complex formation.", "complex formation. it", "formation. it is", "it is expressed", "is expressed on", "expressed on most", "on most lymphocyte", "most lymphocyte populations.", "lymphocyte populations. null", "populations. null mutations", "null mutations of", "mutations of il2rg", "of il2rg in", "il2rg in humans", "in humans cause", "humans cause x", "cause x linked", "x linked severe", "linked severe combined", "severe combined immunodeficiency", "immunodeficiency x", "which has a", "has a phenotype", "a phenotype of", "of severely", "severely reduced t", "reduced t cell", "t cell and", "cell and natural", "and natural killer", "killer nk", "populations but", "but normal numbers", "normal numbers of", "numbers of b", "of b cells.", "b cells. in", "cells. in addition", "in addition to", "addition to reduced", "to reduced t", "t and", "and nk cell", "nk cell numbers", "numbers il2rg", "il2rg knockout mice", "knockout mice also", "mice also have", "also have dramatically", "have dramatically reduced", "dramatically reduced b", "reduced b cell", "b cell populations", "cell populations suggesting", "populations suggesting that", "suggesting that il2rg", "that il2rg is", "il2rg is more", "is more critical", "more critical for", "critical for b", "for b cell", "b cell development", "cell development in", "development in mice", "in mice than", "mice than in", "than in humans.", "in humans. patients", "humans. patients with", "patients with severe", "with severe combined", "immunodeficiency scid", "scid phenotype", "phenotype due to", "due to il7r", "to il7r mutations", "mutations see", "see puel &", "puel & leonard", "& leonard 2000", "or a partial", "a partial deficiency", "partial deficiency of", "deficiency of il7r", "il7r roifman", "roifman et al.", "et al. 2000", "2000 have", "have markedly reduced", "markedly reduced circulating", "reduced circulating t", "circulating t cells", "cells but", "but normal levels", "normal levels of", "levels of peripheral", "of peripheral blood", "peripheral blood b", "blood b cells", "b cells and", "cells and nk", "and nk cells", "cells similar", "similar to the", "to the phenotype", "the phenotype of", "phenotype of il2rg", "of il2rg mutations", "mutations highlighting", "highlighting a requirement", "a requirement for", "requirement for il7", "for il7 in", "il7 in t", "t cell lymphopoiesis.", "cell lymphopoiesis. it", "lymphopoiesis. it has", "it has been", "has been suggested", "been suggested that", "suggested that il7", "that il7 is", "il7 is essential", "is essential for", "essential for murine", "murine but", "but not human", "not human b", "human b cell", "development but", "but recent studies", "recent studies indicate", "studies indicate that", "indicate that il7", "essential for human", "for human b", "b cell production", "cell production from", "production from adult", "from adult bone", "adult bone marrow", "bone marrow and", "marrow and that", "and that il7", "that il7 induced", "il7 induced expansion", "induced expansion of", "expansion of the", "of the progenitor", "the progenitor b", "progenitor b cell", "b cell compartment", "cell compartment is", "compartment is increasingly", "is increasingly critical", "increasingly critical for", "critical for human", "cell production during", "production during later", "during later stages", "later stages of", "stages of development", "development parrish", "parrish et al.", "et al. 2009", "al. 2009 .

il7", "2009 .

il7 has", ".

il7 has been", "has been shown", "been shown to", "shown to induce", "to induce rapid", "induce rapid and", "rapid and dose", "and dose dependent", "dose dependent tyrosine", "dependent tyrosine phosphorylation", "tyrosine phosphorylation of", "phosphorylation of jaks", "of jaks 1", "jaks 1 and", "1 and 3", "3 and", "and concomitantly tyrosine", "concomitantly tyrosine phosphorylation", "tyrosine phosphorylation and", "phosphorylation and dna", "and dna binding", "dna binding activity", "binding activity of", "activity of stat5a/b", "stat5a/b foxwell", "foxwell et al.", "et al. 1995", "al. 1995 .", "1995 . il7r", ". il7r was", "il7r was shown", "was shown to", "shown to directly", "to directly induce", "directly induce the", "induce the activation", "the activation of", "activation of jaks", "of jaks and", "jaks and stats", "and stats by", "stats by van", "by van der", "van der plas", "der plas et", "plas et al.", "1996 . jak1", ". jak1 and", "jak1 and jak3", "and jak3 knockout", "jak3 knockout mice", "knockout mice displayed", "mice displayed severely", "displayed severely impaired", "severely impaired thymic", "impaired thymic development", "development further", "further supporting their", "supporting their importance", "their importance in", "importance in il7", "in il7 signaling", "signaling rodig", "rodig et al.", "et al. 1998", "1998 nosaka", "nosaka et al.", "al. 1995 .

the", "1995 .

the role", ".

the role of", "role of stat5", "of stat5 in", "stat5 in il7", "il7 signaling has", "signaling has been", "has been studied", "been studied largely", "studied largely in", "largely in mouse", "in mouse models.", "mouse models. tyr449", "models. tyr449 in", "tyr449 in the", "in the cytoplasmic", "the cytoplasmic domain", "cytoplasmic domain of", "domain of il7ra", "of il7ra is", "il7ra is required", "is required for", "required for t", "for t cell", "development in vivo", "in vivo and", "vivo and activation", "and activation of", "activation of jak/stat5", "of jak/stat5 and", "jak/stat5 and pi3k/akt", "and pi3k/akt pathways", "pathways jiang", "jiang et al.", "et al. 2004", "2004 pallard", "pallard et al.", "et al. 1999", "al. 1999 .", "1999 . t", ". t cells", "t cells from", "cells from an", "from an il7r", "an il7r y449f", "il7r y449f knock", "y449f knock in", "knock in mouse", "in mouse did", "mouse did not", "did not activate", "not activate stat5", "stat5 osbourne", "osbourne et al.", "indicating that il7", "that il7 regulates", "il7 regulates stat5", "regulates stat5 activity", "stat5 activity via", "activity via this", "via this key", "this key tyrosine", "key tyrosine residue.", "tyrosine residue. stat5", "residue. stat5 seems", "stat5 seems to", "seems to enhance", "to enhance proliferation", "enhance proliferation of", "proliferation of multiple", "of multiple cell", "multiple cell lineages", "cell lineages in", "lineages in mouse", "in mouse models", "mouse models but", "models but it", "but it remains", "it remains unclear", "remains unclear whether", "unclear whether stat5", "whether stat5 is", "stat5 is required", "is required solely", "required solely for", "solely for survival", "for survival signaling", "survival signaling or", "signaling or also", "or also for", "also for the", "for the induction", "the induction of", "induction of proliferative", "of proliferative activity", "activity kittipatarin", "kittipatarin & khaled", "khaled 2007", "2007 .

the model", ".

the model for", "model for il7", "for il7 receptor", "il7 receptor signaling", "receptor signaling is", "signaling is believed", "is believed to", "believed to resemble", "to resemble that", "resemble that of", "that of other", "of other gc", "other gc family", "gc family cytokines", "cytokines based", "based on detailed", "on detailed studies", "detailed studies of", "studies of the", "of the il2", "the il2 receptor", "receptor where", "where il2rb binds", "il2rb binds constitutively", "binds constitutively to", "constitutively to jak1", "to jak1 while", "jak1 while jak3", "while jak3 is", "jak3 is pre", "is pre associated", "pre associated uniquely", "associated uniquely with", "uniquely with the", "with the il2rg", "the il2rg chain.", "il2rg chain. extending", "chain. extending this", "extending this model", "this model to", "model to il7", "to il7 suggests", "il7 suggests a", "suggests a similar", "a similar series", "similar series of", "series of events:", "of events: il7r", "events: il7r constitutively", "il7r constitutively associated", "constitutively associated with", "associated with jak1", "with jak1 binds", "jak1 binds il7", "il7 the", "the resulting trimer", "resulting trimer recruits", "trimer recruits il2rg:jak3", "il2rg:jak3 bringing", "bringing jak1 and", "and jak3 into", "jak3 into proximity.", "into proximity. the", "proximity. the association", "the association of", "association of both", "of both chains", "both chains of", "chains of the", "of the il7", "il7 receptor orients", "receptor orients the", "orients the cytoplasmic", "the cytoplasmic domains", "cytoplasmic domains of", "domains of the", "of the receptor", "the receptor chains", "receptor chains so", "chains so that", "so that their", "that their associated", "their associated kinases", "kinases janus", "janus and phosphatidylinositol", "and phosphatidylinositol 3", "phosphatidylinositol 3 kinases", "kinases can", "can phosphorylate sequence", "phosphorylate sequence elements", "sequence elements on", "elements on the", "on the cytoplasmic", "domains jiang", "et al. 2005", "al. 2005 .", "2005 . jaks", ". jaks have", "jaks have low", "have low intrinsic", "low intrinsic enzymatic", "intrinsic enzymatic activity", "activity but", "but after mutual", "after mutual phosphorylation", "mutual phosphorylation acquire", "phosphorylation acquire much", "acquire much higher", "much higher activity", "activity leading", "leading to phosphorylation", "to phosphorylation of", "phosphorylation of the", "of the critical", "the critical y449", "critical y449 site", "y449 site on", "site on il7r.", "on il7r. this", "il7r. this site", "this site binds", "site binds stat5", "binds stat5 and", "stat5 and possibly", "and possibly other", "possibly other signaling", "other signaling adapters", "adapters they", "they in turn", "in turn become", "turn become phosphorylated", "become phosphorylated by", "phosphorylated by jak1", "by jak1 and/or", "jak1 and/or jak3.", "and/or jak3. phosphorylated", "jak3. phosphorylated stats", "phosphorylated stats translocate", "stats translocate to", "translocate to the", "to the nucleus", "the nucleus and", "nucleus and trigger", "and trigger the", "trigger the transcriptional", "the transcriptional events", "transcriptional events of", "events of their", "of their target", "their target genes.

the", "target genes.

the role", "genes.

the role of", "role of the", "of the pi3k/akt", "the pi3k/akt pathway", "pi3k/akt pathway in", "pathway in il7", "il7 signaling is", "signaling is controversial.", "is controversial. it", "controversial. it is", "it is a", "is a potential", "a potential t", "potential t cell", "t cell survival", "cell survival pathway", "survival pathway because", "pathway because in", "because in many", "in many cell", "many cell types", "cell types pi3k", "types pi3k signaling", "pi3k signaling regulates", "signaling regulates diverse", "regulates diverse cellular", "diverse cellular functions", "cellular functions such", "functions such as", "such as cell", "as cell cycle", "cell cycle progression", "progression transcription", "transcription and", "and metabolism. the", "metabolism. the erk/mapk", "the erk/mapk pathway", "erk/mapk pathway does", "pathway does not", "does not appear", "not appear to", "appear to be", "involved in il7", "signaling crawley", "crawley et al.", "et al. 1996", "al. 1996 .

it", "1996 .

it is", ".

it is not", "is not clear", "not clear how", "clear how il7", "how il7 influences", "il7 influences cell", "influences cell proliferation.", "cell proliferation. in", "proliferation. in the", "in the absence", "the absence of", "absence of a", "of a proliferative", "a proliferative signal", "proliferative signal such", "signal such as", "such as il7", "as il7 or", "il7 or il3", "il3 dependent", "dependent lymphocytes arrest", "lymphocytes arrest in", "arrest in the", "in the g0/g1", "the g0/g1 phase", "g0/g1 phase of", "phase of the", "of the cell", "the cell cycle.", "cell cycle. to", "cycle. to exit", "to exit this", "exit this phase", "phase cells", "cells typically activate", "typically activate specific", "activate specific g1", "specific g1 cyclin", "g1 cyclin dependent", "cyclin dependent kinases/cyclins", "dependent kinases/cyclins and", "kinases/cyclins and down", "and down regulate", "down regulate cell", "regulate cell cycle", "cell cycle inhibitors", "cycle inhibitors such", "inhibitors such as", "such as cyclin", "as cyclin dependent", "cyclin dependent kinase", "dependent kinase inhibitor", "kinase inhibitor 1b", "1b cdkn1b", "cdkn1b or p27kip1", "or p27kip1 .", "p27kip1 . there", ". there is", "there is indirect", "is indirect evidence", "indirect evidence suggesting", "evidence suggesting a", "suggesting a possible", "a possible role", "possible role for", "role for il7", "for il7 stimulated", "il7 stimulated activation", "stimulated activation of", "activation of pi3k/akt", "of pi3k/akt signaling", "signaling obtained", "obtained from transformed", "from transformed cell", "transformed cell lines", "cell lines and", "lines and thymocytes", "thymocytes but", "but not confirmed", "not confirmed by", "confirmed by observations", "by observations using", "observations using primary", "using primary t", "primary t cells", "cells kittipatarin", "2007 . il7", ". il7 withdrawal", "il7 withdrawal results", "withdrawal results in", "results in g1/s", "in g1/s cell", "g1/s cell cycle", "cell cycle arrest", "cycle arrest and", "arrest and is", "and is correlated", "is correlated with", "correlated with loss", "with loss of", "loss of cdk2", "of cdk2 activity", "activity geiselhart", "geiselhart et al.", "et al. 2001", "both events which", "events which are", "which are known", "are known to", "known to be", "to be regulated", "be regulated by", "regulated by the", "by the dephosphorylating", "the dephosphorylating activity", "dephosphorylating activity of", "activity of cdc25a.", "of cdc25a. expression", "cdc25a. expression of", "expression of a", "of a p38", "a p38 mapk", "p38 mapk resistant", "mapk resistant cdc25a", "resistant cdc25a mutant", "cdc25a mutant in", "mutant in an", "in an il", "an il 7", "il 7 dependent", "7 dependent t", "dependent t cell", "t cell line", "cell line as", "line as well", "well as in", "as in peripheral", "peripheral primary", "t cells was", "cells was sufficient", "was sufficient to", "sufficient to sustain", "to sustain cell", "sustain cell survival", "cell survival and", "survival and promote", "and promote cell", "promote cell cycling", "cell cycling for", "cycling for several", "for several days", "several days in", "days in the", "absence of il7", "il7 khaled", "khaled et al.", "2005 . cdkn1b", ". cdkn1b is", "cdkn1b is a", "is a member", "a member of", "member of the", "of the cip/kip", "the cip/kip family", "cip/kip family of", "family of cyclin", "of cyclin dependent", "cyclin dependent cell", "dependent cell cycle", "inhibitors ckis", "ckis that", "that negatively regulates", "negatively regulates the", "regulates the g1/s", "the g1/s transition.", "g1/s transition. in", "transition. in il7", "in il7 dependent", "il7 dependent t", "dependent t cells", "cells the", "the expression of", "expression of cdkn1b", "of cdkn1b was", "cdkn1b was sufficient", "sufficient to cause", "to cause g1", "cause g1 arrest", "g1 arrest in", "in the presence", "the presence of", "presence of il7.", "of il7. withdrawal", "il7. withdrawal of", "withdrawal of il7", "of il7 induced", "il7 induced the", "induced the upregulation", "the upregulation of", "upregulation of cdkn1b", "of cdkn1b and", "cdkn1b and arrested", "and arrested cells", "arrested cells in", "cells in g1", "in g1 while", "g1 while sirna", "while sirna knockout", "sirna knockout of", "knockout of cdkn1b", "of cdkn1b enhanced", "cdkn1b enhanced cell", "enhanced cell cycle", "cell cycle progression.", "cycle progression. however", "however adoptive", "adoptive transfer of", "transfer of cdkn1b", "of cdkn1b deficient", "cdkn1b deficient lymphocytes", "deficient lymphocytes into", "lymphocytes into il7", "into il7 deficient", "il7 deficient mice", "deficient mice indicated", "mice indicated that", "indicated that loss", "that loss of", "loss of cdkn1b", "of cdkn1b could", "cdkn1b could only", "could only partially", "only partially compensate", "partially compensate for", "compensate for the", "for the il7", "the il7 signal", "il7 signal needed", "signal needed by", "needed by t", "by t cells", "t cells to", "cells to expand", "to expand in", "expand in a", "in a lymphopenic", "a lymphopenic environment", "environment li", "li et al.", "so though cdkn1b", "though cdkn1b may", "cdkn1b may be", "may be involved", "involved in negative", "in negative regulation", "negative regulation of", "regulation of the", "the cell cycle", "cell cycle through", "cycle through an", "through an effect", "an effect on", "effect on cdk2", "on cdk2 activity", "activity its", "its absence is", "absence is not", "is not sufficient", "not sufficient to", "sufficient to fully", "to fully induce", "fully induce cell", "induce cell cycling", "cell cycling under", "cycling under lymphopenic", "under lymphopenic conditions.", "interleukin 7 il7", "il7 is produced", "is produced primarily by", "produced primarily by t", "primarily by t zone", "by t zone fibroblastic", "t zone fibroblastic reticular", "zone fibroblastic reticular cells", "fibroblastic reticular cells found", "reticular cells found in", "cells found in lymphoid", "found in lymphoid organs", "lymphoid organs and", "organs and also", "and also expressed by", "also expressed by non", "expressed by non hematopoietic", "by non hematopoietic stromal", "non hematopoietic stromal cells", "hematopoietic stromal cells present", "stromal cells present in", "cells present in other", "present in other tissues", "in other tissues including", "other tissues including the", "tissues including the skin", "the skin intestine", "skin intestine and", "intestine and liver. it", "and liver. it is", "liver. it is an", "it is an essential", "is an essential survival", "an essential survival factor", "essential survival factor for", "survival factor for lymphocytes", "for lymphocytes playing", "lymphocytes playing a", "playing a key anti", "a key anti apoptotic", "key anti apoptotic role", "anti apoptotic role in", "apoptotic role in t", "role in t cell", "in t cell development", "cell development as", "development as well", "as well as mediating", "well as mediating peripheral", "as mediating peripheral t", "mediating peripheral t cell", "peripheral t cell maintenance", "t cell maintenance and", "cell maintenance and proliferation.", "maintenance and proliferation. this", "and proliferation. this dual", "proliferation. this dual function", "this dual function is", "dual function is reflected", "function is reflected in", "is reflected in a", "reflected in a dose", "in a dose response", "a dose response relationship", "dose response relationship that", "response relationship that distinguishes", "relationship that distinguishes the", "that distinguishes the survival", "distinguishes the survival function", "the survival function from", "survival function from the", "function from the proliferative", "from the proliferative activity", "proliferative activity low", "activity low doses", "low doses of il7", "of il7 <1", "il7 <1 ng/ml", "<1 ng/ml sustain", "ng/ml sustain only", "only survival higher", "survival higher doses", "doses >1", ">1 ng/ml promote", "ng/ml promote survival", "promote survival and cell", "survival and cell cycling", "cell cycling kittipatarin", "cycling kittipatarin et", "kittipatarin et al. 2006", "al. 2006 swainson", "2006 swainson et", "swainson et al. 2007", "et al. 2007 .

the", "al. 2007 .

the il7", "2007 .

the il7 receptor", ".

the il7 receptor is", "il7 receptor is a", "receptor is a heterodimeric", "is a heterodimeric complex", "a heterodimeric complex of", "heterodimeric complex of the", "complex of the the", "of the the common", "the the common cytokine", "the common cytokine receptor", "common cytokine receptor gamma", "cytokine receptor gamma chain", "gamma chain il2rg", "cd132 or gc", "or gc and", "gc and the", "and the il7 receptor", "the il7 receptor alpha", "il7 receptor alpha chain", "alpha chain il7r", "il7ra cd127 .", "cd127 . both chains", ". both chains are", "both chains are members", "chains are members of", "are members of the", "members of the type", "of the type 1", "the type 1 cytokine", "type 1 cytokine family.", "1 cytokine family. neither", "cytokine family. neither chain", "family. neither chain is", "neither chain is unique", "chain is unique to", "is unique to the", "unique to the il7", "to the il7 receptor", "the il7 receptor as", "il7 receptor as il7r", "receptor as il7r is", "as il7r is utilized", "il7r is utilized by", "is utilized by the", "utilized by the receptor", "by the receptor for", "the receptor for thymic", "receptor for thymic stromal", "for thymic stromal lymphopoietin", "stromal lymphopoietin tslp", "tslp while il2rg", "while il2rg is shared", "il2rg is shared with", "is shared with the", "shared with the receptors", "with the receptors for", "the receptors for il2", "for il2 il4", "il9 il15 and", "il15 and il21. il2rg", "and il21. il2rg consists", "il21. il2rg consists of", "il2rg consists of a", "consists of a single", "of a single transmembrane", "a single transmembrane region", "single transmembrane region and", "transmembrane region and a", "region and a 240aa", "and a 240aa extracellular", "a 240aa extracellular region", "240aa extracellular region that", "extracellular region that includes", "region that includes a", "that includes a fibronectin", "includes a fibronectin type", "a fibronectin type iii", "type iii fniii", "fniii domain thought", "domain thought to be", "thought to be involved", "to be involved in", "be involved in receptor", "involved in receptor complex", "in receptor complex formation.", "receptor complex formation. it", "complex formation. it is", "formation. it is expressed", "it is expressed on", "is expressed on most", "expressed on most lymphocyte", "on most lymphocyte populations.", "most lymphocyte populations. null", "lymphocyte populations. null mutations", "populations. null mutations of", "null mutations of il2rg", "mutations of il2rg in", "of il2rg in humans", "il2rg in humans cause", "in humans cause x", "humans cause x linked", "cause x linked severe", "x linked severe combined", "linked severe combined immunodeficiency", "combined immunodeficiency x", "immunodeficiency x scid", "scid which", "which has a phenotype", "has a phenotype of", "phenotype of severely", "of severely reduced", "severely reduced t cell", "reduced t cell and", "t cell and natural", "cell and natural killer", "natural killer nk", "nk cell populations", "cell populations but", "populations but normal", "but normal numbers of", "normal numbers of b", "numbers of b cells.", "of b cells. in", "b cells. in addition", "cells. in addition to", "in addition to reduced", "addition to reduced t", "reduced t and", "t and nk", "and nk cell numbers", "cell numbers il2rg", "numbers il2rg knockout", "il2rg knockout mice also", "knockout mice also have", "mice also have dramatically", "also have dramatically reduced", "have dramatically reduced b", "dramatically reduced b cell", "reduced b cell populations", "b cell populations suggesting", "cell populations suggesting that", "populations suggesting that il2rg", "suggesting that il2rg is", "that il2rg is more", "il2rg is more critical", "is more critical for", "more critical for b", "critical for b cell", "for b cell development", "b cell development in", "cell development in mice", "development in mice than", "in mice than in", "mice than in humans.", "than in humans. patients", "in humans. patients with", "humans. patients with severe", "patients with severe combined", "with severe combined immunodeficiency", "combined immunodeficiency scid", "scid phenotype due", "phenotype due to il7r", "due to il7r mutations", "il7r mutations see", "mutations see puel", "see puel & leonard", "puel & leonard 2000", "2000 or", "or a partial deficiency", "a partial deficiency of", "partial deficiency of il7r", "of il7r roifman", "il7r roifman et", "roifman et al. 2000", "al. 2000 have", "2000 have markedly", "have markedly reduced circulating", "markedly reduced circulating t", "reduced circulating t cells", "t cells but", "cells but normal", "but normal levels of", "normal levels of peripheral", "levels of peripheral blood", "of peripheral blood b", "peripheral blood b cells", "blood b cells and", "b cells and nk", "cells and nk cells", "nk cells similar", "cells similar to", "similar to the phenotype", "to the phenotype of", "the phenotype of il2rg", "phenotype of il2rg mutations", "il2rg mutations highlighting", "mutations highlighting a", "highlighting a requirement for", "a requirement for il7", "requirement for il7 in", "for il7 in t", "il7 in t cell", "in t cell lymphopoiesis.", "t cell lymphopoiesis. it", "cell lymphopoiesis. it has", "lymphopoiesis. it has been", "it has been suggested", "has been suggested that", "been suggested that il7", "suggested that il7 is", "that il7 is essential", "il7 is essential for", "is essential for murine", "for murine but", "murine but not", "but not human b", "not human b cell", "human b cell development", "cell development but", "development but recent", "but recent studies indicate", "recent studies indicate that", "studies indicate that il7", "indicate that il7 is", "is essential for human", "essential for human b", "for human b cell", "human b cell production", "b cell production from", "cell production from adult", "production from adult bone", "from adult bone marrow", "adult bone marrow and", "bone marrow and that", "marrow and that il7", "and that il7 induced", "that il7 induced expansion", "il7 induced expansion of", "induced expansion of the", "expansion of the progenitor", "of the progenitor b", "the progenitor b cell", "progenitor b cell compartment", "b cell compartment is", "cell compartment is increasingly", "compartment is increasingly critical", "is increasingly critical for", "increasingly critical for human", "critical for human b", "b cell production during", "cell production during later", "production during later stages", "during later stages of", "later stages of development", "of development parrish", "development parrish et", "parrish et al. 2009", "et al. 2009 .

il7", "al. 2009 .

il7 has", "2009 .

il7 has been", ".

il7 has been shown", "has been shown to", "been shown to induce", "shown to induce rapid", "to induce rapid and", "induce rapid and dose", "rapid and dose dependent", "and dose dependent tyrosine", "dose dependent tyrosine phosphorylation", "dependent tyrosine phosphorylation of", "tyrosine phosphorylation of jaks", "phosphorylation of jaks 1", "of jaks 1 and", "jaks 1 and 3", "and 3 and", "3 and concomitantly", "and concomitantly tyrosine phosphorylation", "concomitantly tyrosine phosphorylation and", "tyrosine phosphorylation and dna", "phosphorylation and dna binding", "and dna binding activity", "dna binding activity of", "binding activity of stat5a/b", "of stat5a/b foxwell", "stat5a/b foxwell et", "foxwell et al. 1995", "et al. 1995 .", "al. 1995 . il7r", "1995 . il7r was", ". il7r was shown", "il7r was shown to", "was shown to directly", "shown to directly induce", "to directly induce the", "directly induce the activation", "induce the activation of", "the activation of jaks", "activation of jaks and", "of jaks and stats", "jaks and stats by", "and stats by van", "stats by van der", "by van der plas", "van der plas et", "der plas et al.", "al. 1996 .", "1996 . jak1 and", ". jak1 and jak3", "jak1 and jak3 knockout", "and jak3 knockout mice", "jak3 knockout mice displayed", "knockout mice displayed severely", "mice displayed severely impaired", "displayed severely impaired thymic", "severely impaired thymic development", "thymic development further", "development further supporting", "further supporting their importance", "supporting their importance in", "their importance in il7", "importance in il7 signaling", "il7 signaling rodig", "signaling rodig et", "rodig et al. 1998", "al. 1998 nosaka", "1998 nosaka et", "nosaka et al. 1995", "et al. 1995 .

the", "al. 1995 .

the role", "1995 .

the role of", ".

the role of stat5", "role of stat5 in", "of stat5 in il7", "stat5 in il7 signaling", "in il7 signaling has", "il7 signaling has been", "signaling has been studied", "has been studied largely", "been studied largely in", "studied largely in mouse", "largely in mouse models.", "in mouse models. tyr449", "mouse models. tyr449 in", "models. tyr449 in the", "tyr449 in the cytoplasmic", "in the cytoplasmic domain", "the cytoplasmic domain of", "cytoplasmic domain of il7ra", "domain of il7ra is", "of il7ra is required", "il7ra is required for", "is required for t", "required for t cell", "for t cell development", "t cell development in", "cell development in vivo", "development in vivo and", "in vivo and activation", "vivo and activation of", "and activation of jak/stat5", "activation of jak/stat5 and", "of jak/stat5 and pi3k/akt", "jak/stat5 and pi3k/akt pathways", "pi3k/akt pathways jiang", "pathways jiang et", "jiang et al. 2004", "al. 2004 pallard", "2004 pallard et", "pallard et al. 1999", "et al. 1999 .", "al. 1999 . t", "1999 . t cells", ". t cells from", "t cells from an", "cells from an il7r", "from an il7r y449f", "an il7r y449f knock", "il7r y449f knock in", "y449f knock in mouse", "knock in mouse did", "in mouse did not", "mouse did not activate", "did not activate stat5", "activate stat5 osbourne", "stat5 osbourne et", "osbourne et al. 2007", "2007 indicating", "indicating that il7 regulates", "that il7 regulates stat5", "il7 regulates stat5 activity", "regulates stat5 activity via", "stat5 activity via this", "activity via this key", "via this key tyrosine", "this key tyrosine residue.", "key tyrosine residue. stat5", "tyrosine residue. stat5 seems", "residue. stat5 seems to", "stat5 seems to enhance", "seems to enhance proliferation", "to enhance proliferation of", "enhance proliferation of multiple", "proliferation of multiple cell", "of multiple cell lineages", "multiple cell lineages in", "cell lineages in mouse", "lineages in mouse models", "in mouse models but", "mouse models but it", "models but it remains", "but it remains unclear", "it remains unclear whether", "remains unclear whether stat5", "unclear whether stat5 is", "whether stat5 is required", "stat5 is required solely", "is required solely for", "required solely for survival", "solely for survival signaling", "for survival signaling or", "survival signaling or also", "signaling or also for", "or also for the", "also for the induction", "for the induction of", "the induction of proliferative", "induction of proliferative activity", "proliferative activity kittipatarin", "activity kittipatarin &", "& khaled 2007", "khaled 2007 .

the", "2007 .

the model for", ".

the model for il7", "model for il7 receptor", "for il7 receptor signaling", "il7 receptor signaling is", "receptor signaling is believed", "signaling is believed to", "is believed to resemble", "believed to resemble that", "to resemble that of", "resemble that of other", "that of other gc", "of other gc family", "other gc family cytokines", "family cytokines based", "cytokines based on", "based on detailed studies", "on detailed studies of", "detailed studies of the", "studies of the il2", "of the il2 receptor", "il2 receptor where", "receptor where il2rb", "where il2rb binds constitutively", "il2rb binds constitutively to", "binds constitutively to jak1", "constitutively to jak1 while", "to jak1 while jak3", "jak1 while jak3 is", "while jak3 is pre", "jak3 is pre associated", "is pre associated uniquely", "pre associated uniquely with", "associated uniquely with the", "uniquely with the il2rg", "with the il2rg chain.", "the il2rg chain. extending", "il2rg chain. extending this", "chain. extending this model", "extending this model to", "this model to il7", "model to il7 suggests", "to il7 suggests a", "il7 suggests a similar", "suggests a similar series", "a similar series of", "similar series of events:", "series of events: il7r", "of events: il7r constitutively", "events: il7r constitutively associated", "il7r constitutively associated with", "constitutively associated with jak1", "associated with jak1 binds", "with jak1 binds il7", "binds il7 the", "il7 the resulting", "the resulting trimer recruits", "resulting trimer recruits il2rg:jak3", "recruits il2rg:jak3 bringing", "il2rg:jak3 bringing jak1", "bringing jak1 and jak3", "jak1 and jak3 into", "and jak3 into proximity.", "jak3 into proximity. the", "into proximity. the association", "proximity. the association of", "the association of both", "association of both chains", "of both chains of", "both chains of the", "chains of the il7", "of the il7 receptor", "the il7 receptor orients", "il7 receptor orients the", "receptor orients the cytoplasmic", "orients the cytoplasmic domains", "the cytoplasmic domains of", "cytoplasmic domains of the", "domains of the receptor", "of the receptor chains", "the receptor chains so", "receptor chains so that", "chains so that their", "so that their associated", "that their associated kinases", "associated kinases janus", "kinases janus and", "janus and phosphatidylinositol 3", "and phosphatidylinositol 3 kinases", "3 kinases can", "kinases can phosphorylate", "can phosphorylate sequence elements", "phosphorylate sequence elements on", "sequence elements on the", "elements on the cytoplasmic", "on the cytoplasmic domains", "cytoplasmic domains jiang", "domains jiang et", "jiang et al. 2005", "et al. 2005 .", "al. 2005 . jaks", "2005 . jaks have", ". jaks have low", "jaks have low intrinsic", "have low intrinsic enzymatic", "low intrinsic enzymatic activity", "enzymatic activity but", "activity but after", "but after mutual phosphorylation", "after mutual phosphorylation acquire", "mutual phosphorylation acquire much", "phosphorylation acquire much higher", "acquire much higher activity", "higher activity leading", "activity leading to", "leading to phosphorylation of", "to phosphorylation of the", "phosphorylation of the critical", "of the critical y449", "the critical y449 site", "critical y449 site on", "y449 site on il7r.", "site on il7r. this", "on il7r. this site", "il7r. this site binds", "this site binds stat5", "site binds stat5 and", "binds stat5 and possibly", "stat5 and possibly other", "and possibly other signaling", "possibly other signaling adapters", "signaling adapters they", "adapters they in", "they in turn become", "in turn become phosphorylated", "turn become phosphorylated by", "become phosphorylated by jak1", "phosphorylated by jak1 and/or", "by jak1 and/or jak3.", "jak1 and/or jak3. phosphorylated", "and/or jak3. phosphorylated stats", "jak3. phosphorylated stats translocate", "phosphorylated stats translocate to", "stats translocate to the", "translocate to the nucleus", "to the nucleus and", "the nucleus and trigger", "nucleus and trigger the", "and trigger the transcriptional", "trigger the transcriptional events", "the transcriptional events of", "transcriptional events of their", "events of their target", "of their target genes.

the", "their target genes.

the role", "target genes.

the role of", "genes.

the role of the", "role of the pi3k/akt", "of the pi3k/akt pathway", "the pi3k/akt pathway in", "pi3k/akt pathway in il7", "pathway in il7 signaling", "in il7 signaling is", "il7 signaling is controversial.", "signaling is controversial. it", "is controversial. it is", "controversial. it is a", "it is a potential", "is a potential t", "a potential t cell", "potential t cell survival", "t cell survival pathway", "cell survival pathway because", "survival pathway because in", "pathway because in many", "because in many cell", "in many cell types", "many cell types pi3k", "cell types pi3k signaling", "types pi3k signaling regulates", "pi3k signaling regulates diverse", "signaling regulates diverse cellular", "regulates diverse cellular functions", "diverse cellular functions such", "cellular functions such as", "functions such as cell", "such as cell cycle", "as cell cycle progression", "cycle progression transcription", "transcription and metabolism.", "and metabolism. the erk/mapk", "metabolism. the erk/mapk pathway", "the erk/mapk pathway does", "erk/mapk pathway does not", "pathway does not appear", "does not appear to", "not appear to be", "appear to be involved", "be involved in il7", "involved in il7 signaling", "il7 signaling crawley", "signaling crawley et", "crawley et al. 1996", "et al. 1996 .

it", "al. 1996 .

it is", "1996 .

it is not", ".

it is not clear", "is not clear how", "not clear how il7", "clear how il7 influences", "how il7 influences cell", "il7 influences cell proliferation.", "influences cell proliferation. in", "cell proliferation. in the", "proliferation. in the absence", "in the absence of", "the absence of a", "absence of a proliferative", "of a proliferative signal", "a proliferative signal such", "proliferative signal such as", "signal such as il7", "such as il7 or", "as il7 or il3", "or il3 dependent", "il3 dependent lymphocytes", "dependent lymphocytes arrest in", "lymphocytes arrest in the", "arrest in the g0/g1", "in the g0/g1 phase", "the g0/g1 phase of", "g0/g1 phase of the", "phase of the cell", "of the cell cycle.", "the cell cycle. to", "cell cycle. to exit", "cycle. to exit this", "to exit this phase", "this phase cells", "phase cells typically", "cells typically activate specific", "typically activate specific g1", "activate specific g1 cyclin", "specific g1 cyclin dependent", "g1 cyclin dependent kinases/cyclins", "cyclin dependent kinases/cyclins and", "dependent kinases/cyclins and down", "kinases/cyclins and down regulate", "and down regulate cell", "down regulate cell cycle", "regulate cell cycle inhibitors", "cell cycle inhibitors such", "cycle inhibitors such as", "inhibitors such as cyclin", "such as cyclin dependent", "as cyclin dependent kinase", "cyclin dependent kinase inhibitor", "dependent kinase inhibitor 1b", "inhibitor 1b cdkn1b", "1b cdkn1b or", "cdkn1b or p27kip1 .", "or p27kip1 . there", "p27kip1 . there is", ". there is indirect", "there is indirect evidence", "is indirect evidence suggesting", "indirect evidence suggesting a", "evidence suggesting a possible", "suggesting a possible role", "a possible role for", "possible role for il7", "role for il7 stimulated", "for il7 stimulated activation", "il7 stimulated activation of", "stimulated activation of pi3k/akt", "activation of pi3k/akt signaling", "pi3k/akt signaling obtained", "signaling obtained from", "obtained from transformed cell", "from transformed cell lines", "transformed cell lines and", "cell lines and thymocytes", "and thymocytes but", "thymocytes but not", "but not confirmed by", "not confirmed by observations", "confirmed by observations using", "by observations using primary", "observations using primary t", "using primary t cells", "t cells kittipatarin", "cells kittipatarin &", "khaled 2007 .", "2007 . il7 withdrawal", ". il7 withdrawal results", "il7 withdrawal results in", "withdrawal results in g1/s", "results in g1/s cell", "in g1/s cell cycle", "g1/s cell cycle arrest", "cell cycle arrest and", "cycle arrest and is", "arrest and is correlated", "and is correlated with", "is correlated with loss", "correlated with loss of", "with loss of cdk2", "loss of cdk2 activity", "cdk2 activity geiselhart", "activity geiselhart et", "geiselhart et al. 2001", "2001 both", "both events which are", "events which are known", "which are known to", "are known to be", "known to be regulated", "to be regulated by", "be regulated by the", "regulated by the dephosphorylating", "by the dephosphorylating activity", "the dephosphorylating activity of", "dephosphorylating activity of cdc25a.", "activity of cdc25a. expression", "of cdc25a. expression of", "cdc25a. expression of a", "expression of a p38", "of a p38 mapk", "a p38 mapk resistant", "p38 mapk resistant cdc25a", "mapk resistant cdc25a mutant", "resistant cdc25a mutant in", "cdc25a mutant in an", "mutant in an il", "in an il 7", "an il 7 dependent", "il 7 dependent t", "7 dependent t cell", "dependent t cell line", "t cell line as", "cell line as well", "line as well as", "as well as in", "well as in peripheral", "in peripheral primary", "peripheral primary t", "primary t cells was", "t cells was sufficient", "cells was sufficient to", "was sufficient to sustain", "sufficient to sustain cell", "to sustain cell survival", "sustain cell survival and", "cell survival and promote", "survival and promote cell", "and promote cell cycling", "promote cell cycling for", "cell cycling for several", "cycling for several days", "for several days in", "several days in the", "days in the absence", "the absence of il7", "of il7 khaled", "il7 khaled et", "khaled et al. 2005", "al. 2005 . cdkn1b", "2005 . cdkn1b is", ". cdkn1b is a", "cdkn1b is a member", "is a member of", "a member of the", "member of the cip/kip", "of the cip/kip family", "the cip/kip family of", "cip/kip family of cyclin", "family of cyclin dependent", "of cyclin dependent cell", "cyclin dependent cell cycle", "dependent cell cycle inhibitors", "cycle inhibitors ckis", "ckis that negatively", "that negatively regulates the", "negatively regulates the g1/s", "regulates the g1/s transition.", "the g1/s transition. in", "g1/s transition. in il7", "transition. in il7 dependent", "in il7 dependent t", "il7 dependent t cells", "t cells the", "cells the expression", "the expression of cdkn1b", "expression of cdkn1b was", "of cdkn1b was sufficient", "cdkn1b was sufficient to", "was sufficient to cause", "sufficient to cause g1", "to cause g1 arrest", "cause g1 arrest in", "g1 arrest in the", "arrest in the presence", "in the presence of", "the presence of il7.", "presence of il7. withdrawal", "of il7. withdrawal of", "il7. withdrawal of il7", "withdrawal of il7 induced", "of il7 induced the", "il7 induced the upregulation", "induced the upregulation of", "the upregulation of cdkn1b", "upregulation of cdkn1b and", "of cdkn1b and arrested", "cdkn1b and arrested cells", "and arrested cells in", "arrested cells in g1", "cells in g1 while", "in g1 while sirna", "g1 while sirna knockout", "while sirna knockout of", "sirna knockout of cdkn1b", "knockout of cdkn1b enhanced", "of cdkn1b enhanced cell", "cdkn1b enhanced cell cycle", "enhanced cell cycle progression.", "cell cycle progression. however", "progression. however adoptive", "however adoptive transfer", "adoptive transfer of cdkn1b", "transfer of cdkn1b deficient", "of cdkn1b deficient lymphocytes", "cdkn1b deficient lymphocytes into", "deficient lymphocytes into il7", "lymphocytes into il7 deficient", "into il7 deficient mice", "il7 deficient mice indicated", "deficient mice indicated that", "mice indicated that loss", "indicated that loss of", "that loss of cdkn1b", "loss of cdkn1b could", "of cdkn1b could only", "cdkn1b could only partially", "could only partially compensate", "only partially compensate for", "partially compensate for the", "compensate for the il7", "for the il7 signal", "the il7 signal needed", "il7 signal needed by", "signal needed by t", "needed by t cells", "by t cells to", "t cells to expand", "cells to expand in", "to expand in a", "expand in a lymphopenic", "in a lymphopenic environment", "lymphopenic environment li", "environment li et", "li et al. 2006", "2006 so", "so though cdkn1b may", "though cdkn1b may be", "cdkn1b may be involved", "may be involved in", "be involved in negative", "involved in negative regulation", "in negative regulation of", "negative regulation of the", "regulation of the cell", "of the cell cycle", "the cell cycle through", "cell cycle through an", "cycle through an effect", "through an effect on", "an effect on cdk2", "effect on cdk2 activity", "cdk2 activity its", "activity its absence", "its absence is not", "absence is not sufficient", "is not sufficient to", "not sufficient to fully", "sufficient to fully induce", "to fully induce cell", "fully induce cell cycling", "induce cell cycling under", "cell cycling under lymphopenic", "cycling under lymphopenic conditions.", "7 il7 is", "il7 is produced primarily", "is produced primarily by t", "produced primarily by t zone", "primarily by t zone fibroblastic", "by t zone fibroblastic reticular", "t zone fibroblastic reticular cells", "zone fibroblastic reticular cells found", "fibroblastic reticular cells found in", "reticular cells found in lymphoid", "cells found in lymphoid organs", "in lymphoid organs and", "lymphoid organs and also", "organs and also expressed", "and also expressed by non", "also expressed by non hematopoietic", "expressed by non hematopoietic stromal", "by non hematopoietic stromal cells", "non hematopoietic stromal cells present", "hematopoietic stromal cells present in", "stromal cells present in other", "cells present in other tissues", "present in other tissues including", "in other tissues including the", "other tissues including the skin", "including the skin intestine", "the skin intestine and", "skin intestine and liver.", "intestine and liver. it is", "and liver. it is an", "liver. it is an essential", "it is an essential survival", "is an essential survival factor", "an essential survival factor for", "essential survival factor for lymphocytes", "factor for lymphocytes playing", "for lymphocytes playing a", "lymphocytes playing a key", "playing a key anti apoptotic", "a key anti apoptotic role", "key anti apoptotic role in", "anti apoptotic role in t", "apoptotic role in t cell", "role in t cell development", "t cell development as", "cell development as well", "development as well as", "as well as mediating peripheral", "well as mediating peripheral t", "as mediating peripheral t cell", "mediating peripheral t cell maintenance", "peripheral t cell maintenance and", "t cell maintenance and proliferation.", "cell maintenance and proliferation. this", "maintenance and proliferation. this dual", "and proliferation. this dual function", "proliferation. this dual function is", "this dual function is reflected", "dual function is reflected in", "function is reflected in a", "is reflected in a dose", "reflected in a dose response", "in a dose response relationship", "a dose response relationship that", "dose response relationship that distinguishes", "response relationship that distinguishes the", "relationship that distinguishes the survival", "that distinguishes the survival function", "distinguishes the survival function from", "the survival function from the", "survival function from the proliferative", "function from the proliferative activity", "the proliferative activity low", "proliferative activity low doses", "activity low doses of", "doses of il7 <1", "of il7 <1 ng/ml", "<1 ng/ml sustain only", "ng/ml sustain only survival", "sustain only survival higher", "only survival higher doses", "higher doses >1", "doses >1 ng/ml", ">1 ng/ml promote survival", "ng/ml promote survival and", "promote survival and cell cycling", "and cell cycling kittipatarin", "cell cycling kittipatarin et", "cycling kittipatarin et al.", "et al. 2006 swainson", "al. 2006 swainson et", "2006 swainson et al.", "swainson et al. 2007 .

the", "et al. 2007 .

the il7", "al. 2007 .

the il7 receptor", "2007 .

the il7 receptor is", ".

the il7 receptor is a", "il7 receptor is a heterodimeric", "receptor is a heterodimeric complex", "is a heterodimeric complex of", "a heterodimeric complex of the", "heterodimeric complex of the the", "complex of the the common", "of the the common cytokine", "the the common cytokine receptor", "the common cytokine receptor gamma", "common cytokine receptor gamma chain", "receptor gamma chain il2rg", "chain il2rg cd132", "il2rg cd132 or", "or gc and the", "gc and the il7", "and the il7 receptor alpha", "the il7 receptor alpha chain", "receptor alpha chain il7r", "chain il7r il7ra", "il7r il7ra cd127", "il7ra cd127 . both", "cd127 . both chains are", ". both chains are members", "both chains are members of", "chains are members of the", "are members of the type", "members of the type 1", "of the type 1 cytokine", "the type 1 cytokine family.", "type 1 cytokine family. neither", "1 cytokine family. neither chain", "cytokine family. neither chain is", "family. neither chain is unique", "neither chain is unique to", "chain is unique to the", "is unique to the il7", "unique to the il7 receptor", "to the il7 receptor as", "the il7 receptor as il7r", "il7 receptor as il7r is", "receptor as il7r is utilized", "as il7r is utilized by", "il7r is utilized by the", "is utilized by the receptor", "utilized by the receptor for", "by the receptor for thymic", "the receptor for thymic stromal", "receptor for thymic stromal lymphopoietin", "thymic stromal lymphopoietin tslp", "lymphopoietin tslp while", "tslp while il2rg is", "while il2rg is shared with", "il2rg is shared with the", "is shared with the receptors", "shared with the receptors for", "with the receptors for il2", "receptors for il2 il4", "il2 il4 il9", "il4 il9 il15", "il9 il15 and il21.", "il15 and il21. il2rg consists", "and il21. il2rg consists of", "il21. il2rg consists of a", "il2rg consists of a single", "consists of a single transmembrane", "of a single transmembrane region", "a single transmembrane region and", "single transmembrane region and a", "transmembrane region and a 240aa", "region and a 240aa extracellular", "and a 240aa extracellular region", "a 240aa extracellular region that", "240aa extracellular region that includes", "extracellular region that includes a", "region that includes a fibronectin", "that includes a fibronectin type", "includes a fibronectin type iii", "fibronectin type iii fniii", "iii fniii domain", "fniii domain thought to", "domain thought to be involved", "thought to be involved in", "to be involved in receptor", "be involved in receptor complex", "involved in receptor complex formation.", "in receptor complex formation. it", "receptor complex formation. it is", "complex formation. it is expressed", "formation. it is expressed on", "it is expressed on most", "is expressed on most lymphocyte", "expressed on most lymphocyte populations.", "on most lymphocyte populations. null", "most lymphocyte populations. null mutations", "lymphocyte populations. null mutations of", "populations. null mutations of il2rg", "null mutations of il2rg in", "mutations of il2rg in humans", "of il2rg in humans cause", "il2rg in humans cause x", "in humans cause x linked", "humans cause x linked severe", "cause x linked severe combined", "x linked severe combined immunodeficiency", "severe combined immunodeficiency x", "combined immunodeficiency x scid", "x scid which", "scid which has", "which has a phenotype of", "a phenotype of severely", "phenotype of severely reduced", "of severely reduced t", "severely reduced t cell and", "reduced t cell and natural", "t cell and natural killer", "and natural killer nk", "killer nk cell", "cell populations but normal", "populations but normal numbers", "but normal numbers of b", "normal numbers of b cells.", "numbers of b cells. in", "of b cells. in addition", "b cells. in addition to", "cells. in addition to reduced", "in addition to reduced t", "to reduced t and", "reduced t and nk", "t and nk cell", "nk cell numbers il2rg", "cell numbers il2rg knockout", "numbers il2rg knockout mice", "il2rg knockout mice also have", "knockout mice also have dramatically", "mice also have dramatically reduced", "also have dramatically reduced b", "have dramatically reduced b cell", "dramatically reduced b cell populations", "reduced b cell populations suggesting", "b cell populations suggesting that", "cell populations suggesting that il2rg", "populations suggesting that il2rg is", "suggesting that il2rg is more", "that il2rg is more critical", "il2rg is more critical for", "is more critical for b", "more critical for b cell", "critical for b cell development", "for b cell development in", "b cell development in mice", "cell development in mice than", "development in mice than in", "in mice than in humans.", "mice than in humans. patients", "than in humans. patients with", "in humans. patients with severe", "humans. patients with severe combined", "patients with severe combined immunodeficiency", "severe combined immunodeficiency scid", "immunodeficiency scid phenotype", "scid phenotype due to", "phenotype due to il7r mutations", "to il7r mutations see", "il7r mutations see puel", "mutations see puel &", "see puel & leonard 2000", "leonard 2000 or", "2000 or a", "or a partial deficiency of", "a partial deficiency of il7r", "deficiency of il7r roifman", "of il7r roifman et", "il7r roifman et al.", "et al. 2000 have", "al. 2000 have markedly", "2000 have markedly reduced", "have markedly reduced circulating t", "markedly reduced circulating t cells", "circulating t cells but", "t cells but normal", "cells but normal levels", "but normal levels of peripheral", "normal levels of peripheral blood", "levels of peripheral blood b", "of peripheral blood b cells", "peripheral blood b cells and", "blood b cells and nk", "b cells and nk cells", "and nk cells similar", "nk cells similar to", "cells similar to the", "similar to the phenotype of", "to the phenotype of il2rg", "the phenotype of il2rg mutations", "of il2rg mutations highlighting", "il2rg mutations highlighting a", "mutations highlighting a requirement", "highlighting a requirement for il7", "a requirement for il7 in", "requirement for il7 in t", "for il7 in t cell", "il7 in t cell lymphopoiesis.", "in t cell lymphopoiesis. it", "t cell lymphopoiesis. it has", "cell lymphopoiesis. it has been", "lymphopoiesis. it has been suggested", "it has been suggested that", "has been suggested that il7", "been suggested that il7 is", "suggested that il7 is essential", "that il7 is essential for", "il7 is essential for murine", "essential for murine but", "for murine but not", "murine but not human", "but not human b cell", "not human b cell development", "b cell development but", "cell development but recent", "development but recent studies", "but recent studies indicate that", "recent studies indicate that il7", "studies indicate that il7 is", "indicate that il7 is essential", "il7 is essential for human", "is essential for human b", "essential for human b cell", "for human b cell production", "human b cell production from", "b cell production from adult", "cell production from adult bone", "production from adult bone marrow", "from adult bone marrow and", "adult bone marrow and that", "bone marrow and that il7", "marrow and that il7 induced", "and that il7 induced expansion", "that il7 induced expansion of", "il7 induced expansion of the", "induced expansion of the progenitor", "expansion of the progenitor b", "of the progenitor b cell", "the progenitor b cell compartment", "progenitor b cell compartment is", "b cell compartment is increasingly", "cell compartment is increasingly critical", "compartment is increasingly critical for", "is increasingly critical for human", "increasingly critical for human b", "critical for human b cell", "human b cell production during", "b cell production during later", "cell production during later stages", "production during later stages of", "during later stages of development", "stages of development parrish", "of development parrish et", "development parrish et al.", "parrish et al. 2009 .

il7", "et al. 2009 .

il7 has", "al. 2009 .

il7 has been", "2009 .

il7 has been shown", ".

il7 has been shown to", "has been shown to induce", "been shown to induce rapid", "shown to induce rapid and", "to induce rapid and dose", "induce rapid and dose dependent", "rapid and dose dependent tyrosine", "and dose dependent tyrosine phosphorylation", "dose dependent tyrosine phosphorylation of", "dependent tyrosine phosphorylation of jaks", "tyrosine phosphorylation of jaks 1", "phosphorylation of jaks 1 and", "of jaks 1 and 3", "1 and 3 and", "and 3 and concomitantly", "3 and concomitantly tyrosine", "and concomitantly tyrosine phosphorylation and", "concomitantly tyrosine phosphorylation and dna", "tyrosine phosphorylation and dna binding", "phosphorylation and dna binding activity", "and dna binding activity of", "dna binding activity of stat5a/b", "activity of stat5a/b foxwell", "of stat5a/b foxwell et", "stat5a/b foxwell et al.", "foxwell et al. 1995 .", "et al. 1995 . il7r", "al. 1995 . il7r was", "1995 . il7r was shown", ". il7r was shown to", "il7r was shown to directly", "was shown to directly induce", "shown to directly induce the", "to directly induce the activation", "directly induce the activation of", "induce the activation of jaks", "the activation of jaks and", "activation of jaks and stats", "of jaks and stats by", "jaks and stats by van", "and stats by van der", "stats by van der plas", "by van der plas et", "van der plas et al.", "plas et al. 1996", "et al. 1996 .", "al. 1996 . jak1", "1996 . jak1 and jak3", ". jak1 and jak3 knockout", "jak1 and jak3 knockout mice", "and jak3 knockout mice displayed", "jak3 knockout mice displayed severely", "knockout mice displayed severely impaired", "mice displayed severely impaired thymic", "displayed severely impaired thymic development", "impaired thymic development further", "thymic development further supporting", "development further supporting their", "further supporting their importance in", "supporting their importance in il7", "their importance in il7 signaling", "in il7 signaling rodig", "il7 signaling rodig et", "signaling rodig et al.", "et al. 1998 nosaka", "al. 1998 nosaka et", "1998 nosaka et al.", "nosaka et al. 1995 .

the", "et al. 1995 .

the role", "al. 1995 .

the role of", "1995 .

the role of stat5", ".

the role of stat5 in", "role of stat5 in il7", "of stat5 in il7 signaling", "stat5 in il7 signaling has", "in il7 signaling has been", "il7 signaling has been studied", "signaling has been studied largely", "has been studied largely in", "been studied largely in mouse", "studied largely in mouse models.", "largely in mouse models. tyr449", "in mouse models. tyr449 in", "mouse models. tyr449 in the", "models. tyr449 in the cytoplasmic", "tyr449 in the cytoplasmic domain", "in the cytoplasmic domain of", "the cytoplasmic domain of il7ra", "cytoplasmic domain of il7ra is", "domain of il7ra is required", "of il7ra is required for", "il7ra is required for t", "is required for t cell", "required for t cell development", "for t cell development in", "t cell development in vivo", "cell development in vivo and", "development in vivo and activation", "in vivo and activation of", "vivo and activation of jak/stat5", "and activation of jak/stat5 and", "activation of jak/stat5 and pi3k/akt", "of jak/stat5 and pi3k/akt pathways", "and pi3k/akt pathways jiang", "pi3k/akt pathways jiang et", "pathways jiang et al.", "et al. 2004 pallard", "al. 2004 pallard et", "2004 pallard et al.", "pallard et al. 1999 .", "et al. 1999 . t", "al. 1999 . t cells", "1999 . t cells from", ". t cells from an", "t cells from an il7r", "cells from an il7r y449f", "from an il7r y449f knock", "an il7r y449f knock in", "il7r y449f knock in mouse", "y449f knock in mouse did", "knock in mouse did not", "in mouse did not activate", "mouse did not activate stat5", "not activate stat5 osbourne", "activate stat5 osbourne et", "stat5 osbourne et al.", "al. 2007 indicating", "2007 indicating that", "indicating that il7 regulates stat5", "that il7 regulates stat5 activity", "il7 regulates stat5 activity via", "regulates stat5 activity via this", "stat5 activity via this key", "activity via this key tyrosine", "via this key tyrosine residue.", "this key tyrosine residue. stat5", "key tyrosine residue. stat5 seems", "tyrosine residue. stat5 seems to", "residue. stat5 seems to enhance", "stat5 seems to enhance proliferation", "seems to enhance proliferation of", "to enhance proliferation of multiple", "enhance proliferation of multiple cell", "proliferation of multiple cell lineages", "of multiple cell lineages in", "multiple cell lineages in mouse", "cell lineages in mouse models", "lineages in mouse models but", "in mouse models but it", "mouse models but it remains", "models but it remains unclear", "but it remains unclear whether", "it remains unclear whether stat5", "remains unclear whether stat5 is", "unclear whether stat5 is required", "whether stat5 is required solely", "stat5 is required solely for", "is required solely for survival", "required solely for survival signaling", "solely for survival signaling or", "for survival signaling or also", "survival signaling or also for", "signaling or also for the", "or also for the induction", "also for the induction of", "for the induction of proliferative", "the induction of proliferative activity", "of proliferative activity kittipatarin", "proliferative activity kittipatarin &", "activity kittipatarin & khaled", "kittipatarin & khaled 2007", "& khaled 2007 .

the", "khaled 2007 .

the model", "2007 .

the model for il7", ".

the model for il7 receptor", "model for il7 receptor signaling", "for il7 receptor signaling is", "il7 receptor signaling is believed", "receptor signaling is believed to", "signaling is believed to resemble", "is believed to resemble that", "believed to resemble that of", "to resemble that of other", "resemble that of other gc", "that of other gc family", "of other gc family cytokines", "gc family cytokines based", "family cytokines based on", "cytokines based on detailed", "based on detailed studies of", "on detailed studies of the", "detailed studies of the il2", "studies of the il2 receptor", "the il2 receptor where", "il2 receptor where il2rb", "receptor where il2rb binds", "where il2rb binds constitutively to", "il2rb binds constitutively to jak1", "binds constitutively to jak1 while", "constitutively to jak1 while jak3", "to jak1 while jak3 is", "jak1 while jak3 is pre", "while jak3 is pre associated", "jak3 is pre associated uniquely", "is pre associated uniquely with", "pre associated uniquely with the", "associated uniquely with the il2rg", "uniquely with the il2rg chain.", "with the il2rg chain. extending", "the il2rg chain. extending this", "il2rg chain. extending this model", "chain. extending this model to", "extending this model to il7", "this model to il7 suggests", "model to il7 suggests a", "to il7 suggests a similar", "il7 suggests a similar series", "suggests a similar series of", "a similar series of events:", "similar series of events: il7r", "series of events: il7r constitutively", "of events: il7r constitutively associated", "events: il7r constitutively associated with", "il7r constitutively associated with jak1", "constitutively associated with jak1 binds", "associated with jak1 binds il7", "jak1 binds il7 the", "binds il7 the resulting", "il7 the resulting trimer", "the resulting trimer recruits il2rg:jak3", "trimer recruits il2rg:jak3 bringing", "recruits il2rg:jak3 bringing jak1", "il2rg:jak3 bringing jak1 and", "bringing jak1 and jak3 into", "jak1 and jak3 into proximity.", "and jak3 into proximity. the", "jak3 into proximity. the association", "into proximity. the association of", "proximity. the association of both", "the association of both chains", "association of both chains of", "of both chains of the", "both chains of the il7", "chains of the il7 receptor", "of the il7 receptor orients", "the il7 receptor orients the", "il7 receptor orients the cytoplasmic", "receptor orients the cytoplasmic domains", "orients the cytoplasmic domains of", "the cytoplasmic domains of the", "cytoplasmic domains of the receptor", "domains of the receptor chains", "of the receptor chains so", "the receptor chains so that", "receptor chains so that their", "chains so that their associated", "so that their associated kinases", "their associated kinases janus", "associated kinases janus and", "kinases janus and phosphatidylinositol", "janus and phosphatidylinositol 3 kinases", "phosphatidylinositol 3 kinases can", "3 kinases can phosphorylate", "kinases can phosphorylate sequence", "can phosphorylate sequence elements on", "phosphorylate sequence elements on the", "sequence elements on the cytoplasmic", "elements on the cytoplasmic domains", "the cytoplasmic domains jiang", "cytoplasmic domains jiang et", "domains jiang et al.", "jiang et al. 2005 .", "et al. 2005 . jaks", "al. 2005 . jaks have", "2005 . jaks have low", ". jaks have low intrinsic", "jaks have low intrinsic enzymatic", "have low intrinsic enzymatic activity", "intrinsic enzymatic activity but", "enzymatic activity but after", "activity but after mutual", "but after mutual phosphorylation acquire", "after mutual phosphorylation acquire much", "mutual phosphorylation acquire much higher", "phosphorylation acquire much higher activity", "much higher activity leading", "higher activity leading to", "activity leading to phosphorylation", "leading to phosphorylation of the", "to phosphorylation of the critical", "phosphorylation of the critical y449", "of the critical y449 site", "the critical y449 site on", "critical y449 site on il7r.", "y449 site on il7r. this", "site on il7r. this site", "on il7r. this site binds", "il7r. this site binds stat5", "this site binds stat5 and", "site binds stat5 and possibly", "binds stat5 and possibly other", "stat5 and possibly other signaling", "and possibly other signaling adapters", "other signaling adapters they", "signaling adapters they in", "adapters they in turn", "they in turn become phosphorylated", "in turn become phosphorylated by", "turn become phosphorylated by jak1", "become phosphorylated by jak1 and/or", "phosphorylated by jak1 and/or jak3.", "by jak1 and/or jak3. phosphorylated", "jak1 and/or jak3. phosphorylated stats", "and/or jak3. phosphorylated stats translocate", "jak3. phosphorylated stats translocate to", "phosphorylated stats translocate to the", "stats translocate to the nucleus", "translocate to the nucleus and", "to the nucleus and trigger", "the nucleus and trigger the", "nucleus and trigger the transcriptional", "and trigger the transcriptional events", "trigger the transcriptional events of", "the transcriptional events of their", "transcriptional events of their target", "events of their target genes.

the", "of their target genes.

the role", "their target genes.

the role of", "target genes.

the role of the", "genes.

the role of the pi3k/akt", "role of the pi3k/akt pathway", "of the pi3k/akt pathway in", "the pi3k/akt pathway in il7", "pi3k/akt pathway in il7 signaling", "pathway in il7 signaling is", "in il7 signaling is controversial.", "il7 signaling is controversial. it", "signaling is controversial. it is", "is controversial. it is a", "controversial. it is a potential", "it is a potential t", "is a potential t cell", "a potential t cell survival", "potential t cell survival pathway", "t cell survival pathway because", "cell survival pathway because in", "survival pathway because in many", "pathway because in many cell", "because in many cell types", "in many cell types pi3k", "many cell types pi3k signaling", "cell types pi3k signaling regulates", "types pi3k signaling regulates diverse", "pi3k signaling regulates diverse cellular", "signaling regulates diverse cellular functions", "regulates diverse cellular functions such", "diverse cellular functions such as", "cellular functions such as cell", "functions such as cell cycle", "such as cell cycle progression", "cell cycle progression transcription", "progression transcription and", "transcription and metabolism. the", "and metabolism. the erk/mapk pathway", "metabolism. the erk/mapk pathway does", "the erk/mapk pathway does not", "erk/mapk pathway does not appear", "pathway does not appear to", "does not appear to be", "not appear to be involved", "appear to be involved in", "to be involved in il7", "be involved in il7 signaling", "in il7 signaling crawley", "il7 signaling crawley et", "signaling crawley et al.", "crawley et al. 1996 .

it", "et al. 1996 .

it is", "al. 1996 .

it is not", "1996 .

it is not clear", ".

it is not clear how", "is not clear how il7", "not clear how il7 influences", "clear how il7 influences cell", "how il7 influences cell proliferation.", "il7 influences cell proliferation. in", "influences cell proliferation. in the", "cell proliferation. in the absence", "proliferation. in the absence of", "in the absence of a", "the absence of a proliferative", "absence of a proliferative signal", "of a proliferative signal such", "a proliferative signal such as", "proliferative signal such as il7", "signal such as il7 or", "such as il7 or il3", "il7 or il3 dependent", "or il3 dependent lymphocytes", "il3 dependent lymphocytes arrest", "dependent lymphocytes arrest in the", "lymphocytes arrest in the g0/g1", "arrest in the g0/g1 phase", "in the g0/g1 phase of", "the g0/g1 phase of the", "g0/g1 phase of the cell", "phase of the cell cycle.", "of the cell cycle. to", "the cell cycle. to exit", "cell cycle. to exit this", "cycle. to exit this phase", "exit this phase cells", "this phase cells typically", "phase cells typically activate", "cells typically activate specific g1", "typically activate specific g1 cyclin", "activate specific g1 cyclin dependent", "specific g1 cyclin dependent kinases/cyclins", "g1 cyclin dependent kinases/cyclins and", "cyclin dependent kinases/cyclins and down", "dependent kinases/cyclins and down regulate", "kinases/cyclins and down regulate cell", "and down regulate cell cycle", "down regulate cell cycle inhibitors", "regulate cell cycle inhibitors such", "cell cycle inhibitors such as", "cycle inhibitors such as cyclin", "inhibitors such as cyclin dependent", "such as cyclin dependent kinase", "as cyclin dependent kinase inhibitor", "cyclin dependent kinase inhibitor 1b", "kinase inhibitor 1b cdkn1b", "inhibitor 1b cdkn1b or", "1b cdkn1b or p27kip1", "cdkn1b or p27kip1 . there", "or p27kip1 . there is", "p27kip1 . there is indirect", ". there is indirect evidence", "there is indirect evidence suggesting", "is indirect evidence suggesting a", "indirect evidence suggesting a possible", "evidence suggesting a possible role", "suggesting a possible role for", "a possible role for il7", "possible role for il7 stimulated", "role for il7 stimulated activation", "for il7 stimulated activation of", "il7 stimulated activation of pi3k/akt", "stimulated activation of pi3k/akt signaling", "of pi3k/akt signaling obtained", "pi3k/akt signaling obtained from", "signaling obtained from transformed", "obtained from transformed cell lines", "from transformed cell lines and", "transformed cell lines and thymocytes", "lines and thymocytes but", "and thymocytes but not", "thymocytes but not confirmed", "but not confirmed by observations", "not confirmed by observations using", "confirmed by observations using primary", "by observations using primary t", "observations using primary t cells", "primary t cells kittipatarin", "t cells kittipatarin &", "cells kittipatarin & khaled", "& khaled 2007 .", "khaled 2007 . il7", "2007 . il7 withdrawal results", ". il7 withdrawal results in", "il7 withdrawal results in g1/s", "withdrawal results in g1/s cell", "results in g1/s cell cycle", "in g1/s cell cycle arrest", "g1/s cell cycle arrest and", "cell cycle arrest and is", "cycle arrest and is correlated", "arrest and is correlated with", "and is correlated with loss", "is correlated with loss of", "correlated with loss of cdk2", "with loss of cdk2 activity", "of cdk2 activity geiselhart", "cdk2 activity geiselhart et", "activity geiselhart et al.", "al. 2001 both", "2001 both events", "both events which are known", "events which are known to", "which are known to be", "are known to be regulated", "known to be regulated by", "to be regulated by the", "be regulated by the dephosphorylating", "regulated by the dephosphorylating activity", "by the dephosphorylating activity of", "the dephosphorylating activity of cdc25a.", "dephosphorylating activity of cdc25a. expression", "activity of cdc25a. expression of", "of cdc25a. expression of a", "cdc25a. expression of a p38", "expression of a p38 mapk", "of a p38 mapk resistant", "a p38 mapk resistant cdc25a", "p38 mapk resistant cdc25a mutant", "mapk resistant cdc25a mutant in", "resistant cdc25a mutant in an", "cdc25a mutant in an il", "mutant in an il 7", "in an il 7 dependent", "an il 7 dependent t", "il 7 dependent t cell", "7 dependent t cell line", "dependent t cell line as", "t cell line as well", "cell line as well as", "line as well as in", "as well as in peripheral", "as in peripheral primary", "in peripheral primary t", "peripheral primary t cells", "primary t cells was sufficient", "t cells was sufficient to", "cells was sufficient to sustain", "was sufficient to sustain cell", "sufficient to sustain cell survival", "to sustain cell survival and", "sustain cell survival and promote", "cell survival and promote cell", "survival and promote cell cycling", "and promote cell cycling for", "promote cell cycling for several", "cell cycling for several days", "cycling for several days in", "for several days in the", "several days in the absence", "days in the absence of", "in the absence of il7", "absence of il7 khaled", "of il7 khaled et", "il7 khaled et al.", "khaled et al. 2005 .", "et al. 2005 . cdkn1b", "al. 2005 . cdkn1b is", "2005 . cdkn1b is a", ". cdkn1b is a member", "cdkn1b is a member of", "is a member of the", "a member of the cip/kip", "member of the cip/kip family", "of the cip/kip family of", "the cip/kip family of cyclin", "cip/kip family of cyclin dependent", "family of cyclin dependent cell", "of cyclin dependent cell cycle", "cyclin dependent cell cycle inhibitors", "cell cycle inhibitors ckis", "inhibitors ckis that", "ckis that negatively regulates", "that negatively regulates the g1/s", "negatively regulates the g1/s transition.", "regulates the g1/s transition. in", "the g1/s transition. in il7", "g1/s transition. in il7 dependent", "transition. in il7 dependent t", "in il7 dependent t cells", "dependent t cells the", "t cells the expression", "cells the expression of", "the expression of cdkn1b was", "expression of cdkn1b was sufficient", "of cdkn1b was sufficient to", "cdkn1b was sufficient to cause", "was sufficient to cause g1", "sufficient to cause g1 arrest", "to cause g1 arrest in", "cause g1 arrest in the", "g1 arrest in the presence", "arrest in the presence of", "in the presence of il7.", "the presence of il7. withdrawal", "presence of il7. withdrawal of", "of il7. withdrawal of il7", "il7. withdrawal of il7 induced", "withdrawal of il7 induced the", "of il7 induced the upregulation", "il7 induced the upregulation of", "induced the upregulation of cdkn1b", "the upregulation of cdkn1b and", "upregulation of cdkn1b and arrested", "of cdkn1b and arrested cells", "cdkn1b and arrested cells in", "and arrested cells in g1", "arrested cells in g1 while", "cells in g1 while sirna", "in g1 while sirna knockout", "g1 while sirna knockout of", "while sirna knockout of cdkn1b", "sirna knockout of cdkn1b enhanced", "knockout of cdkn1b enhanced cell", "of cdkn1b enhanced cell cycle", "cdkn1b enhanced cell cycle progression.", "enhanced cell cycle progression. however", "cycle progression. however adoptive", "progression. however adoptive transfer", "however adoptive transfer of", "adoptive transfer of cdkn1b deficient", "transfer of cdkn1b deficient lymphocytes", "of cdkn1b deficient lymphocytes into", "cdkn1b deficient lymphocytes into il7", "deficient lymphocytes into il7 deficient", "lymphocytes into il7 deficient mice", "into il7 deficient mice indicated", "il7 deficient mice indicated that", "deficient mice indicated that loss", "mice indicated that loss of", "indicated that loss of cdkn1b", "that loss of cdkn1b could", "loss of cdkn1b could only", "of cdkn1b could only partially", "cdkn1b could only partially compensate", "could only partially compensate for", "only partially compensate for the", "partially compensate for the il7", "compensate for the il7 signal", "for the il7 signal needed", "the il7 signal needed by", "il7 signal needed by t", "signal needed by t cells", "needed by t cells to", "by t cells to expand", "t cells to expand in", "cells to expand in a", "to expand in a lymphopenic", "expand in a lymphopenic environment", "a lymphopenic environment li", "lymphopenic environment li et", "environment li et al.", "al. 2006 so", "2006 so though", "so though cdkn1b may be", "though cdkn1b may be involved", "cdkn1b may be involved in", "may be involved in negative", "be involved in negative regulation", "involved in negative regulation of", "in negative regulation of the", "negative regulation of the cell", "regulation of the cell cycle", "of the cell cycle through", "the cell cycle through an", "cell cycle through an effect", "cycle through an effect on", "through an effect on cdk2", "an effect on cdk2 activity", "on cdk2 activity its", "cdk2 activity its absence", "activity its absence is", "its absence is not sufficient", "absence is not sufficient to", "is not sufficient to fully", "not sufficient to fully induce", "sufficient to fully induce cell", "to fully induce cell cycling", "fully induce cell cycling under", "induce cell cycling under lymphopenic", "cell cycling under lymphopenic conditions." ] }, { "record_id": "GLY_000594_1_39", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1268020", "r hsa", "hsa 1268020", "r hsa 1268020" ] }, { "record_id": "GLY_000594_1_39", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitochondrial protein", "protein import", "mitochondrial protein import", "a human", "human mitochondrion", "mitochondrion contains", "contains about", "about 1500", "1500 proteins", "more than", "than 99%", "99% of", "of which", "which are", "are encoded", "encoded in", "in the", "the nucleus", "synthesized in", "the cytosol", "cytosol and", "and imported", "imported into", "into the", "the mitochondrion.", "mitochondrion. proteins", "proteins are", "are targeted", "targeted to", "to four", "four locations", "outer membrane", "intermembrane space", "inner membrane", "and matrix", "and must", "must be", "be sorted", "sorted accordingly", "reviewed in", "in kutik", "kutik et", "et al.", "al. 2007", "milenkovic et", "bolender et", "al. 2008", "endo and", "and yamano", "yamano 2009", "wiedemann and", "and pfanner", "pfanner 2017", "kang et", "al. 2018", "2018 .", ". newly", "newly synthesized", "synthesized proteins", "are transported", "transported from", "from the", "cytosol across", "across the", "the outer", "membrane by", "by the", "the tomm40:tomm70", "tomm40:tomm70 complex.", "complex. proteins", "proteins that", "that contain", "contain presequences", "presequences first", "first interact", "interact with", "with the", "the tomm20", "tomm20 subunit", "subunit of", "of the", "the complex", "complex while", "while proteins", "contain internal", "internal targeting", "targeting elements", "elements first", "the tomm70", "tomm70 subunit.", "subunit. after", "after initial", "initial interaction", "interaction the", "the protein", "protein is", "is conducted", "conducted across", "by tomm40", "tomm40 subunits.", "subunits. in", "in yeast", "yeast some", "some proteins", "proteins such", "such as", "as aco1", "and atp2", "atp2 have", "have both", "both presequences", "presequences that", "that interact", "with tom20", "tom20 and", "and mature", "mature regions", "regions that", "with tom70", "yamamoto et", "al. 2009", "2009 .
after", ".
after passage", "passage across", "proteins may", "may be", "be targeted", "to the", "membrane via", "via the", "the samm50", "samm50 complex", "the inner", "the timm22", "timm22 or", "or timm23", "timm23 complexes", "in van", "van der", "der laan", "laan et", "al. 2010", "the matrix", "matrix via", "the timm23", "timm23 complex", "or proteins", "may fold", "fold and", "and remain", "remain in", "the intermembrane", "in stojanovski", "stojanovski et", "deponte and", "and hell", "hell 2009", "sideris and", "and tokatlidis", "tokatlidis 2010", "2010 .", ". presequences", "presequences on", "on matrix", "matrix and", "and inner", "membrane proteins", "proteins cause", "cause interaction", "interaction with", "with timm23", "targeting sequences", "sequences cause", "cause outer", "proteins to", "to interact", "complex and", "timm22 complex.", "complex. while", "while in", "space hydrophobic", "hydrophobic proteins", "are chaperoned", "chaperoned by", "the timm8:timm13", "timm8:timm13 complex", "complex and/or", "and/or the", "the timm9:timm10:fxc1", "timm9:timm10:fxc1 complex.", "a human mitochondrion", "human mitochondrion contains", "mitochondrion contains about", "contains about 1500", "about 1500 proteins", "proteins more", "more than 99%", "than 99% of", "99% of which", "of which are", "which are encoded", "are encoded in", "encoded in the", "in the nucleus", "nucleus synthesized", "synthesized in the", "in the cytosol", "the cytosol and", "cytosol and imported", "and imported into", "imported into the", "into the mitochondrion.", "the mitochondrion. proteins", "mitochondrion. proteins are", "proteins are targeted", "are targeted to", "targeted to four", "to four locations", "locations outer", "membrane intermembrane", "space inner", "membrane and", "and must be", "must be sorted", "be sorted accordingly", "accordingly reviewed", "reviewed in kutik", "in kutik et", "kutik et al.", "et al. 2007", "2007 milenkovic", "milenkovic et al.", "2007 bolender", "bolender et al.", "et al. 2008", "2008 endo", "endo and yamano", "and yamano 2009", "2009 wiedemann", "wiedemann and pfanner", "and pfanner 2017", "2017 kang", "kang et al.", "et al. 2018", "al. 2018 .", "2018 . newly", ". newly synthesized", "newly synthesized proteins", "synthesized proteins are", "proteins are transported", "are transported from", "transported from the", "from the cytosol", "the cytosol across", "cytosol across the", "across the outer", "the outer membrane", "outer membrane by", "membrane by the", "by the tomm40:tomm70", "the tomm40:tomm70 complex.", "tomm40:tomm70 complex. proteins", "complex. proteins that", "proteins that contain", "that contain presequences", "contain presequences first", "presequences first interact", "first interact with", "interact with the", "with the tomm20", "the tomm20 subunit", "tomm20 subunit of", "subunit of the", "of the complex", "the complex while", "complex while proteins", "while proteins that", "that contain internal", "contain internal targeting", "internal targeting elements", "targeting elements first", "elements first interact", "with the tomm70", "the tomm70 subunit.", "tomm70 subunit. after", "subunit. after initial", "after initial interaction", "initial interaction the", "interaction the protein", "the protein is", "protein is conducted", "is conducted across", "conducted across the", "membrane by tomm40", "by tomm40 subunits.", "tomm40 subunits. in", "subunits. in yeast", "in yeast some", "yeast some proteins", "some proteins such", "proteins such as", "such as aco1", "aco1 atp1", "atp1 cit1", "cit1 idh1", "idh1 and", "and atp2 have", "atp2 have both", "have both presequences", "both presequences that", "presequences that interact", "that interact with", "interact with tom20", "with tom20 and", "tom20 and mature", "and mature regions", "mature regions that", "regions that interact", "interact with tom70", "tom70 yamamoto", "yamamoto et al.", "et al. 2009", "al. 2009 .
after", "2009 .
after passage", ".
after passage across", "passage across the", "proteins may be", "may be targeted", "be targeted to", "targeted to the", "to the outer", "outer membrane via", "membrane via the", "via the samm50", "the samm50 complex", "complex to", "to the inner", "the inner membrane", "inner membrane via", "via the timm22", "the timm22 or", "timm22 or timm23", "or timm23 complexes", "complexes reviewed", "reviewed in van", "in van der", "van der laan", "der laan et", "laan et al.", "et al. 2010", "to the matrix", "the matrix via", "matrix via the", "via the timm23", "the timm23 complex", "complex reviewed", "or proteins may", "proteins may fold", "may fold and", "fold and remain", "and remain in", "remain in the", "in the intermembrane", "the intermembrane space", "space reviewed", "reviewed in stojanovski", "in stojanovski et", "stojanovski et al.", "2008 deponte", "deponte and hell", "and hell 2009", "sideris and tokatlidis", "and tokatlidis 2010", "tokatlidis 2010 .", "2010 . presequences", ". presequences on", "presequences on matrix", "on matrix and", "matrix and inner", "and inner membrane", "inner membrane proteins", "membrane proteins cause", "proteins cause interaction", "cause interaction with", "interaction with timm23", "with timm23 complexes", "complexes internal", "internal targeting sequences", "targeting sequences cause", "sequences cause outer", "cause outer membrane", "outer membrane proteins", "membrane proteins to", "proteins to interact", "to interact with", "with the samm50", "samm50 complex and", "complex and inner", "with the timm22", "the timm22 complex.", "timm22 complex. while", "complex. while in", "while in the", "intermembrane space hydrophobic", "space hydrophobic proteins", "hydrophobic proteins are", "proteins are chaperoned", "are chaperoned by", "chaperoned by the", "by the timm8:timm13", "the timm8:timm13 complex", "timm8:timm13 complex and/or", "complex and/or the", "and/or the timm9:timm10:fxc1", "the timm9:timm10:fxc1 complex.", "a human mitochondrion contains", "human mitochondrion contains about", "mitochondrion contains about 1500", "contains about 1500 proteins", "1500 proteins more", "proteins more than", "more than 99% of", "than 99% of which", "99% of which are", "of which are encoded", "which are encoded in", "are encoded in the", "encoded in the nucleus", "the nucleus synthesized", "nucleus synthesized in", "synthesized in the cytosol", "in the cytosol and", "the cytosol and imported", "cytosol and imported into", "and imported into the", "imported into the mitochondrion.", "into the mitochondrion. proteins", "the mitochondrion. proteins are", "mitochondrion. proteins are targeted", "proteins are targeted to", "are targeted to four", "targeted to four locations", "four locations outer", "locations outer membrane", "outer membrane intermembrane", "membrane intermembrane space", "intermembrane space inner", "space inner membrane", "inner membrane and", "membrane and matrix", "and matrix and", "matrix and must", "and must be sorted", "must be sorted accordingly", "sorted accordingly reviewed", "accordingly reviewed in", "reviewed in kutik et", "in kutik et al.", "kutik et al. 2007", "al. 2007 milenkovic", "2007 milenkovic et", "milenkovic et al. 2007", "al. 2007 bolender", "2007 bolender et", "bolender et al. 2008", "al. 2008 endo", "2008 endo and", "endo and yamano 2009", "yamano 2009 wiedemann", "2009 wiedemann and", "wiedemann and pfanner 2017", "pfanner 2017 kang", "2017 kang et", "kang et al. 2018", "et al. 2018 .", "al. 2018 . newly", "2018 . newly synthesized", ". newly synthesized proteins", "newly synthesized proteins are", "synthesized proteins are transported", "proteins are transported from", "are transported from the", "transported from the cytosol", "from the cytosol across", "the cytosol across the", "cytosol across the outer", "across the outer membrane", "the outer membrane by", "outer membrane by the", "membrane by the tomm40:tomm70", "by the tomm40:tomm70 complex.", "the tomm40:tomm70 complex. proteins", "tomm40:tomm70 complex. proteins that", "complex. proteins that contain", "proteins that contain presequences", "that contain presequences first", "contain presequences first interact", "presequences first interact with", "first interact with the", "interact with the tomm20", "with the tomm20 subunit", "the tomm20 subunit of", "tomm20 subunit of the", "subunit of the complex", "of the complex while", "the complex while proteins", "complex while proteins that", "while proteins that contain", "proteins that contain internal", "that contain internal targeting", "contain internal targeting elements", "internal targeting elements first", "targeting elements first interact", "elements first interact with", "interact with the tomm70", "with the tomm70 subunit.", "the tomm70 subunit. after", "tomm70 subunit. after initial", "subunit. after initial interaction", "after initial interaction the", "initial interaction the protein", "interaction the protein is", "the protein is conducted", "protein is conducted across", "is conducted across the", "conducted across the outer", "outer membrane by tomm40", "membrane by tomm40 subunits.", "by tomm40 subunits. in", "tomm40 subunits. in yeast", "subunits. in yeast some", "in yeast some proteins", "yeast some proteins such", "some proteins such as", "proteins such as aco1", "as aco1 atp1", "idh1 and atp2", "and atp2 have both", "atp2 have both presequences", "have both presequences that", "both presequences that interact", "presequences that interact with", "that interact with tom20", "interact with tom20 and", "with tom20 and mature", "tom20 and mature regions", "and mature regions that", "mature regions that interact", "regions that interact with", "that interact with tom70", "with tom70 yamamoto", "tom70 yamamoto et", "yamamoto et al. 2009", "et al. 2009 .
after", "al. 2009 .
after passage", "2009 .
after passage across", ".
after passage across the", "passage across the outer", "membrane proteins may", "proteins may be targeted", "may be targeted to", "be targeted to the", "targeted to the outer", "to the outer membrane", "the outer membrane via", "outer membrane via the", "membrane via the samm50", "via the samm50 complex", "samm50 complex to", "complex to the", "to the inner membrane", "the inner membrane via", "inner membrane via the", "membrane via the timm22", "via the timm22 or", "the timm22 or timm23", "timm22 or timm23 complexes", "timm23 complexes reviewed", "complexes reviewed in", "reviewed in van der", "in van der laan", "van der laan et", "der laan et al.", "laan et al. 2010", "2010 to", "to the matrix via", "the matrix via the", "matrix via the timm23", "via the timm23 complex", "timm23 complex reviewed", "complex reviewed in", "2010 or", "or proteins may fold", "proteins may fold and", "may fold and remain", "fold and remain in", "and remain in the", "remain in the intermembrane", "in the intermembrane space", "intermembrane space reviewed", "space reviewed in", "reviewed in stojanovski et", "in stojanovski et al.", "stojanovski et al. 2008", "al. 2008 deponte", "2008 deponte and", "deponte and hell 2009", "2009 sideris", "sideris and tokatlidis 2010", "and tokatlidis 2010 .", "tokatlidis 2010 . presequences", "2010 . presequences on", ". presequences on matrix", "presequences on matrix and", "on matrix and inner", "matrix and inner membrane", "and inner membrane proteins", "inner membrane proteins cause", "membrane proteins cause interaction", "proteins cause interaction with", "cause interaction with timm23", "interaction with timm23 complexes", "timm23 complexes internal", "complexes internal targeting", "internal targeting sequences cause", "targeting sequences cause outer", "sequences cause outer membrane", "cause outer membrane proteins", "outer membrane proteins to", "membrane proteins to interact", "proteins to interact with", "to interact with the", "interact with the samm50", "with the samm50 complex", "the samm50 complex and", "samm50 complex and inner", "complex and inner membrane", "inner membrane proteins to", "interact with the timm22", "with the timm22 complex.", "the timm22 complex. while", "timm22 complex. while in", "complex. while in the", "while in the intermembrane", "the intermembrane space hydrophobic", "intermembrane space hydrophobic proteins", "space hydrophobic proteins are", "hydrophobic proteins are chaperoned", "proteins are chaperoned by", "are chaperoned by the", "chaperoned by the timm8:timm13", "by the timm8:timm13 complex", "the timm8:timm13 complex and/or", "timm8:timm13 complex and/or the", "complex and/or the timm9:timm10:fxc1", "and/or the timm9:timm10:fxc1 complex.", "a human mitochondrion contains about", "human mitochondrion contains about 1500", "mitochondrion contains about 1500 proteins", "about 1500 proteins more", "1500 proteins more than", "proteins more than 99%", "more than 99% of which", "than 99% of which are", "99% of which are encoded", "of which are encoded in", "which are encoded in the", "are encoded in the nucleus", "in the nucleus synthesized", "the nucleus synthesized in", "nucleus synthesized in the", "synthesized in the cytosol and", "in the cytosol and imported", "the cytosol and imported into", "cytosol and imported into the", "and imported into the mitochondrion.", "imported into the mitochondrion. proteins", "into the mitochondrion. proteins are", "the mitochondrion. proteins are targeted", "mitochondrion. proteins are targeted to", "proteins are targeted to four", "are targeted to four locations", "to four locations outer", "four locations outer membrane", "outer membrane intermembrane space", "intermembrane space inner membrane", "inner membrane and matrix", "and matrix and must", "matrix and must be", "and must be sorted accordingly", "be sorted accordingly reviewed", "sorted accordingly reviewed in", "accordingly reviewed in kutik", "reviewed in kutik et al.", "in kutik et al. 2007", "et al. 2007 milenkovic", "al. 2007 milenkovic et", "2007 milenkovic et al.", "et al. 2007 bolender", "al. 2007 bolender et", "2007 bolender et al.", "et al. 2008 endo", "al. 2008 endo and", "2008 endo and yamano", "and yamano 2009 wiedemann", "yamano 2009 wiedemann and", "2009 wiedemann and pfanner", "and pfanner 2017 kang", "pfanner 2017 kang et", "2017 kang et al.", "kang et al. 2018 .", "et al. 2018 . newly", "al. 2018 . newly synthesized", "2018 . newly synthesized proteins", ". newly synthesized proteins are", "newly synthesized proteins are transported", "synthesized proteins are transported from", "proteins are transported from the", "are transported from the cytosol", "transported from the cytosol across", "from the cytosol across the", "the cytosol across the outer", "cytosol across the outer membrane", "across the outer membrane by", "the outer membrane by the", "outer membrane by the tomm40:tomm70", "membrane by the tomm40:tomm70 complex.", "by the tomm40:tomm70 complex. proteins", "the tomm40:tomm70 complex. proteins that", "tomm40:tomm70 complex. proteins that contain", "complex. proteins that contain presequences", "proteins that contain presequences first", "that contain presequences first interact", "contain presequences first interact with", "presequences first interact with the", "first interact with the tomm20", "interact with the tomm20 subunit", "with the tomm20 subunit of", "the tomm20 subunit of the", "tomm20 subunit of the complex", "subunit of the complex while", "of the complex while proteins", "the complex while proteins that", "complex while proteins that contain", "while proteins that contain internal", "proteins that contain internal targeting", "that contain internal targeting elements", "contain internal targeting elements first", "internal targeting elements first interact", "targeting elements first interact with", "elements first interact with the", "first interact with the tomm70", "interact with the tomm70 subunit.", "with the tomm70 subunit. after", "the tomm70 subunit. after initial", "tomm70 subunit. after initial interaction", "subunit. after initial interaction the", "after initial interaction the protein", "initial interaction the protein is", "interaction the protein is conducted", "the protein is conducted across", "protein is conducted across the", "is conducted across the outer", "conducted across the outer membrane", "the outer membrane by tomm40", "outer membrane by tomm40 subunits.", "membrane by tomm40 subunits. in", "by tomm40 subunits. in yeast", "tomm40 subunits. in yeast some", "subunits. in yeast some proteins", "in yeast some proteins such", "yeast some proteins such as", "some proteins such as aco1", "such as aco1 atp1", "aco1 atp1 cit1", "atp1 cit1 idh1", "cit1 idh1 and", "idh1 and atp2 have", "and atp2 have both presequences", "atp2 have both presequences that", "have both presequences that interact", "both presequences that interact with", "presequences that interact with tom20", "that interact with tom20 and", "interact with tom20 and mature", "with tom20 and mature regions", "tom20 and mature regions that", "and mature regions that interact", "mature regions that interact with", "regions that interact with tom70", "interact with tom70 yamamoto", "with tom70 yamamoto et", "tom70 yamamoto et al.", "yamamoto et al. 2009 .
after", "et al. 2009 .
after passage", "al. 2009 .
after passage across", "2009 .
after passage across the", ".
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female reproductive tract is", "female reproductive tract is rheotaxis." ] }, { "record_id": "GLY_000594_1_44", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1306955", "r hsa", "hsa 1306955", "r hsa 1306955" ] }, { "record_id": "GLY_000594_1_44", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "grb7 events", "events in", "in erbb2", "erbb2 signaling", "grb7 events in", "events in erbb2", "in erbb2 signaling", "grb7 events in erbb2", "events in erbb2 signaling", "grb7 events in erbb2 signaling", "heterodimers of", "of erbb2", "erbb2 and", "and erbb3", "erbb3 are", "are able", "able to", "to bind", "bind grb7", "fiddes et", "et al.", "al. 1998", "through phosphorylated", "phosphorylated tyrosine", "tyrosine residues", "residues in", "in the", "the c", "c tail", "tail of", "of erbb3", "y1199 and", "and y1262", "but the", "the exact", "exact downstream", "downstream signaling", "signaling of", "of 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the", "2010 .

the caspase", ".

the caspase 8", "caspase 8 zymogens", "8 zymogens are", "zymogens are present", "are present in", "present in the", "in the cells", "the cells as", "cells as inactive", "as inactive monomers", "monomers which", "which are recruited", "are recruited to", "recruited to the", "to the death", "the death inducing", "death inducing signaling", "inducing signaling complex", "complex disc", "disc by", "by homophilic interactions", "homophilic interactions with", "interactions with the", "with the ded", "the ded domain", "ded domain of", "domain of fadd.", "of fadd. the", "fadd. the monomeric", "the monomeric zymogens", "monomeric zymogens undergo", "zymogens undergo dimerization", "undergo dimerization and", "dimerization and the", "and the subsequent", "the subsequent conformational", "subsequent conformational changes", "conformational changes at", "changes at the", "at the receptor", "the receptor complex", "complex which", "which results in", "results in the", "in the formation", "formation of catalytically", "of catalytically active", "catalytically active form", "active form of", "form of procaspase", "of procaspase 8.", "procaspase 8. boatright", "8. boatright km", "boatright km et", "km et al", "et al 2003", "2003 donepudi", "donepudi m et", "m et al", "al 2010 .", "caspase 8 is synthesized", "8 is synthesized as", "is synthesized as zymogen", "as zymogen procaspase", "zymogen procaspase 8", "procaspase 8 and", "8 and is", "and is formed from", "is formed from procaspase", "formed from procaspase 8", "from procaspase 8 as", "procaspase 8 as a", "8 as a cleavage", "as a cleavage product.", "a cleavage product. however", "product. however the", "however the cleavage", "the cleavage itself appears", "cleavage itself appears not", "itself appears not to", "appears not to be", "not to be sufficient", "to be sufficient for", "be sufficient for the", "sufficient for the formation", "for the formation of", "the formation of an", "formation of an active", "of an active caspase", "an active caspase 8.", "active caspase 8. only", "caspase 8. only the", "8. only the coordinated", "only the coordinated dimerization", "the coordinated dimerization and", "coordinated dimerization and cleavage", "dimerization and cleavage of", "and cleavage of the", "cleavage of the zymogen", "of the zymogen produce", "the zymogen produce efficient", "zymogen produce efficient activation", "produce efficient activation in", "efficient activation in vitro", "activation in vitro and", "in vitro and apoptosis", "vitro and apoptosis in", "and apoptosis in cellular", "apoptosis in cellular systems", "cellular systems boatright", "systems boatright km", "boatright km and salvesen", "km and salvesen gs", "and salvesen gs 2003", "gs 2003 keller", "2003 keller n", "keller n et al", "n et al 2010", "al 2010 oberst", "2010 oberst a", "oberst a et al", "a et al 2010", "et al 2010 .

the", "al 2010 .

the caspase", "2010 .

the caspase 8", ".

the caspase 8 zymogens", "caspase 8 zymogens are", "8 zymogens are present", "zymogens are present in", "are present in the", "present in the cells", "in the cells as", "the cells as inactive", "cells as inactive monomers", "inactive monomers which", "monomers which are", "which are recruited to", "are recruited to the", "recruited to the death", "to the death inducing", "the death inducing signaling", "death inducing signaling complex", "signaling complex disc", "disc by homophilic", "by homophilic interactions with", "homophilic interactions with the", "interactions with the ded", "with the ded domain", "the ded domain of", "ded domain of fadd.", "domain of fadd. the", "of fadd. the monomeric", "fadd. the monomeric zymogens", "the monomeric zymogens undergo", "monomeric zymogens undergo dimerization", "zymogens undergo dimerization and", "undergo dimerization and the", "dimerization and the subsequent", "and the subsequent conformational", "the subsequent conformational changes", "subsequent conformational changes at", "conformational changes at the", "changes at the receptor", "at the receptor complex", "receptor complex which", "complex which results", "which results in the", "results in the formation", "in the formation of", "the formation of catalytically", "formation of catalytically active", "of catalytically active form", "catalytically active form of", "active form of procaspase", "form of procaspase 8.", "of procaspase 8. boatright", "procaspase 8. boatright km", "8. boatright km et", "boatright km et al", "km et al 2003", "al 2003 donepudi", "2003 donepudi m", "donepudi m et al", "m et al 2003", "al 2003 keller", "et al 2010 .", "caspase 8 is synthesized as", "8 is synthesized as zymogen", "synthesized as zymogen procaspase", "as zymogen procaspase 8", "procaspase 8 and is", "8 and is formed", "and is formed from procaspase", "is formed from procaspase 8", "formed from procaspase 8 as", "from procaspase 8 as a", "procaspase 8 as a cleavage", "8 as a cleavage product.", "as a cleavage product. however", "cleavage product. however the", "product. however the cleavage", "however the cleavage itself", "the cleavage itself appears not", "cleavage itself appears not to", "itself appears not to be", "appears not to be sufficient", "not to be sufficient for", "to be sufficient for the", "be sufficient for the formation", "sufficient for the formation of", "for the formation of an", "the formation of an active", "formation of an active caspase", "of an active caspase 8.", "an active caspase 8. only", "active caspase 8. only the", "caspase 8. only the coordinated", "8. only the coordinated dimerization", "only the coordinated dimerization and", "the coordinated dimerization and cleavage", "coordinated dimerization and cleavage of", "dimerization and cleavage of the", "and cleavage of the zymogen", "cleavage of the zymogen produce", "of the zymogen produce efficient", "the zymogen produce efficient activation", "zymogen produce efficient activation in", "produce efficient activation in vitro", "efficient activation in vitro and", "activation in vitro and apoptosis", "in vitro and apoptosis in", "vitro and apoptosis in cellular", "and apoptosis in cellular systems", "in cellular systems boatright", "cellular systems boatright km", "systems boatright km and", "boatright km and salvesen gs", "km and salvesen gs 2003", "salvesen gs 2003 keller", "gs 2003 keller n", "2003 keller n et", "keller n et al 2010", "et al 2010 oberst", "al 2010 oberst a", "2010 oberst a et", "oberst a et al 2010", "a et al 2010 .

the", "et al 2010 .

the caspase", "al 2010 .

the caspase 8", "2010 .

the caspase 8 zymogens", ".

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the", "ronnstrand 2006 . the receptor", "2006 . the receptor for", ". the receptor for scf", "the receptor for scf is", "receptor for scf is kit", "scf is kit a", "is kit a tyrosine", "kit a tyrosine kinase", "tyrosine kinase receptor rtk", "receptor rtk closely", "rtk closely related to", "closely related to the receptors", "related to the receptors for", "to the receptors for platelet", "the receptors for platelet derived", "receptors for platelet derived growth", "for platelet derived growth factor", "platelet derived growth factor receptor", "growth factor receptor colony", "factor receptor colony stimulating", "receptor colony stimulating factor", "stimulating factor 1 linnekin", "factor 1 linnekin 1999", "linnekin 1999 and flt3", "and flt3 rosnet et", "flt3 rosnet et al.", "rosnet et al. 1991 .", "al. 1991 . four", "1991 . four isoforms", ". four isoforms of", "four isoforms of c kit", "isoforms of c kit have", "of c kit have been", "c kit have been identified", "kit have been identified in", "have been identified in humans.", "been identified in humans. alternative", "identified in humans. alternative splicing", "in humans. alternative splicing results", "humans. alternative splicing results in", "alternative splicing results in isoforms", "splicing results in isoforms of", "results in isoforms of kit", "in isoforms of kit differing", "isoforms of kit differing in", "of kit differing in the", "kit differing in the presence", "differing in the presence or", "in the presence or absence", "the presence or absence of", "presence or absence of four", "or absence of four residues", "of four residues gnnk", "residues gnnk in", "gnnk in the extracellular", "in the extracellular region. this", "the extracellular region. this occurs", "extracellular region. this occurs due", "region. this occurs due to", "this occurs due to the", "occurs due to the use", "due to the use of", "to the use of an", "the use of an alternate", "use of an alternate 5'", "of an alternate 5' splice", "an alternate 5' splice donor", "alternate 5' splice donor site.", "5' splice donor site. these", "splice donor site. these gnnk+", "donor site. these gnnk+ and", "site. these gnnk+ and gnnk", "gnnk+ and gnnk variants", "and gnnk variants are", "gnnk variants are co", "variants are co expressed in", "are co expressed in most", "co expressed in most tissues", "in most tissues the", "most tissues the gnnk", "the gnnk form predominates", "gnnk form predominates and", "form predominates and was more", "predominates and was more strongly", "and was more strongly tyrosine", "was more strongly tyrosine phosphorylated", "more strongly tyrosine phosphorylated and", "strongly tyrosine phosphorylated and more", "tyrosine phosphorylated and more rapidly", "phosphorylated and more rapidly internalized", "more rapidly internalized ronnstrand", "rapidly internalized ronnstrand 2004", "internalized ronnstrand 2004 .", "ronnstrand 2004 . there are", "2004 . there are also", ". there are also splice", "there are also splice variants", "are also splice variants that", "also splice variants that arise", "splice variants that arise from", "variants that arise from alternative", "that arise from alternative usage", "arise from alternative usage of", "from alternative usage of splice", "alternative usage of splice acceptor", "usage of splice acceptor site", "of splice acceptor site resulting", "splice acceptor site resulting in", "acceptor site resulting in the", "site resulting in the presence", "resulting in the presence or", "presence or absence of a", "or absence of a serine", "absence of a serine residue", "a serine residue crosier", "serine residue crosier et", "residue crosier et al.", "crosier et al. 1993", "et al. 1993 .", "al. 1993 . finally", "1993 . finally there", ". finally there is", "finally there is an", "there is an alternative shorter", "is an alternative shorter transcript", "an alternative shorter transcript of", "alternative shorter transcript of kit", "shorter transcript of kit expressed", "transcript of kit expressed in", "of kit expressed in postmeiotic", "kit expressed in postmeiotic germ", "expressed in postmeiotic germ cells", "in postmeiotic germ cells in", "postmeiotic germ cells in the", "germ cells in the testis", "in the testis which", "the testis which encodes", "testis which encodes a", "which encodes a truncated kit", "encodes a truncated kit consisting", "a truncated kit consisting only", "truncated kit consisting only of", "kit consisting only of the", "consisting only of the second", "only of the second part", "of the second part of", "the second part of the", "second part of the kinase", "part of the kinase domain", "of the kinase domain and", "the kinase domain and thus", "kinase domain and thus lackig", "domain and thus lackig the", "and thus lackig the extracellular", "thus lackig the extracellular and", "lackig the extracellular and transmembrane", "the extracellular and transmembrane domains", "extracellular and transmembrane domains as", "and transmembrane domains as well", "transmembrane domains as well as", "domains as well as the", "as well as the first", "well as the first part", "as the first part of", "the first part of the", "first part of the kinase", "the kinase domain rossi", "kinase domain rossi et", "domain rossi et al.", "rossi et al. 1991 .", "et al. 1991 . binding", "1991 . binding of", ". binding of scf", "binding of scf homodimers", "of scf homodimers to kit", "scf homodimers to kit results", "homodimers to kit results in", "to kit results in kit", "kit results in kit homodimerization", "results in kit homodimerization followed", "in kit homodimerization followed by", "kit homodimerization followed by activation", "homodimerization followed by activation of", "followed by activation of its", "by activation of its intrinsic", "activation of its intrinsic tyrosine", "of its intrinsic tyrosine kinase", "its intrinsic tyrosine kinase activity.", "intrinsic tyrosine kinase activity. kit", "tyrosine kinase activity. kit stimulation", "kinase activity. kit stimulation activates", "activity. kit stimulation activates a", "kit stimulation activates a wide", "stimulation activates a wide array", "activates a wide array of", "a wide array of signalling", "wide array of signalling pathways", "array of signalling pathways including", "of signalling pathways including mapk", "pathways including mapk pi3k", "including mapk pi3k and", "mapk pi3k and jak/stat", "pi3k and jak/stat reber", "and jak/stat reber et", "jak/stat reber et al.", "et al. 2006 ronnstrand", "al. 2006 ronnstrand 2004", "2006 ronnstrand 2004 .", "ronnstrand 2004 . defects of", "2004 . defects of kit", ". defects of kit in", "defects of kit in humans", "of kit in humans are", "kit in humans are associated", "in humans are associated with", "humans are associated with different", "are associated with different genetic", "associated with different genetic diseases", "with different genetic diseases 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1442490", "r hsa 1442490" ] }, { "record_id": "GLY_000594_1_55", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "collagen degradation", "collagen fibril", "fibril diameter", "diameter and", "and spatial", "spatial organisation", "organisation are", "are dependent", "dependent on", "on the", "the species", "tissue type", "type and", "and stage", "stage of", "of development", "parry 1988", "1988 .", ". the", "the lengths", "lengths of", "of collagen", "collagen fibrils", "fibrils in", "in mature", "mature tissues", "tissues are", "are largely", "largely unknown", "unknown but", "but in", "in tendon", "tendon can", "can be", "be measured", "measured in", "in millimetres", "craig et", "et al.", "al. 1989", "1989 .", ". collagen", "fibrils isolated", "isolated from", "from adult", "adult bovine", "bovine corneal", "corneal stroma", "stroma had", "had ~350", "~350 collagen", "collagen molecules", "molecules in", "in transverse", "transverse section", "tapering down", "down to", "to three", "three molecules", "molecules at", "at the", "the growing", "growing tip", "holmes &", "& kadler", "kadler 2005", "2005 .", ".

the", "

the classical", "classical view", "view of", "of collagenases", "collagenases is", "is that", "that they", "they actively", "actively unwind", "unwind the", "the triple", "triple helical", "helical chain", "a process", "process termed", "termed molecular", "molecular tectonics", "overall 2002", "bode &", "& maskos", "maskos 2003", "before preferentially", "preferentially cleaving", "cleaving the", "the alpha2", "alpha2 chain", "chain followed", "followed by", "by the", "the remaining", "remaining chains", "chung et", "al. 2004", "2004 .", ". more", "more recently", "recently it", "it has", "has been", "been suggested", "suggested that", "that collagen", "fibrils exist", "exist in", "in an", "an equilibrium", "equilibrium between", "between protected", "protected and", "and vulnerable", "vulnerable states", "stultz 2002", "nerenberg &", "& stultz", "stultz 2008", "2008 .", "the prototypical", "prototypical triple", "helical structure", "structure of", "collagen does", "does not", "not fit", "fit into", "into the", "the active", "active site", "site of", "of collagenase", "collagenase mmps.", "mmps. in", "in addition", "addition the", "the scissile", "scissile bonds", "bonds are", "are not", "not solvent", "solvent exposed", "exposed and", "and are", "are therefore", "therefore inaccessible", "inaccessible to", "to the", "the collagenase", "collagenase active", "2002 .", ". it", "it was", "was realized", "realized that", "collagen must", "must locally", "locally unfold", "unfold into", "into non", "non triple", "helical regions", "regions to", "to allow", "allow collagenolysis.", "collagenolysis. observations", "observations using", "using circular", "circular dichroism", "dichroism and", "and differential", "differential scanning", "scanning calorimetry", "calorimetry confirm", "confirm that", "that there", "there is", "is considerable", "considerable heterogeneity", "heterogeneity along", "along collagen", "collagen fibres", "makareeva et", "al. 2008", "allowing access", "access for", "for mmps", "mmps at", "at physiological", "physiological temperatures", "salsas escat", "escat et", "al. 2010", "2010 .

collagen", ".

collagen fibrils", "fibrils with", "with cut", "cut chains", "chains are", "are unstable", "unstable and", "and accessible", "accessible to", "to proteinases", "proteinases that", "that cannot", "cannot cleave", "cleave intact", "intact collagen", "collagen strands", "woessner &", "& nagase", "nagase 2000", "somerville et", "al. 2003", "2003 .", ". continued", "continued degradation", "degradation leads", "leads to", "the formation", "formation of", "of gelatin", "lovejoy et", "al. 1999", "1999 .", ". degradation", "degradation of", "collagen types", "types other", "other than", "than i", "i iii", "iii is", "is less", "less well", "well characterized", "characterized but", "but believed", "believed to", "to occur", "occur in", "in a", "a similar", "similar manner.", "manner.

metalloproteinases", "play a", "a major", "major part", "part in", "in the", "the degradation", "of several", "several extracellular", "extracellular macromolecules", "macromolecules including", "including collagens.", "collagens. mmp1", "welgus et", "al. 1981", "hasty et", "al. 1987", "and mmp13", "knauper et", "al. 1996", "sometimes referred", "referred to", "to as", "as collagenases", "collagenases i", "ii and", "and iii", "iii respectively", "are able", "able to", "to initiate", "initiate the", "the intrahelical", "intrahelical cleavage", "cleavage of", "of the", "the major", "major fibril", "fibril forming", "forming collagens", "collagens i", "iii at", "at neutral", "neutral ph", "and thus", "thus thought", "thought to", "to define", "define the", "the rate", "rate limiting", "limiting step", "step in", "in normal", "normal tissue", "tissue remodeling", "remodeling events.", "events. all", "all can", "can cleave", "cleave additional", "substrates including", "including other", "other collagen", "collagen subtypes.", "subtypes. collagenases", "collagenases cut", "cut collagen", "collagen alpha", "alpha chains", "chains at", "at a", "a single", "single conserved", "conserved gly", "gly ile/leu", "ile/leu site", "site approximately", "approximately 3/4", "3/4 of", "the molecule's", "molecule's length", "length from", "from the", "the n", "n terminus", "fields 1991", "the cleavage", "cleavage site", "site is", "is characterised", "characterised by", "the motif", "g i/l", "the g", "i/l bond", "bond is", "is cleaved.", "cleaved. in", "in collagen", "collagen type", "type i", "i this", "this corresponds", "corresponds to", "to g953", "g953 i954", "i954 in", "the uniprot", "uniprot canonical", "canonical alpha", "alpha chain", "chain sequences", "often given", "given as", "as g775", "g775 i776", "i776 in", "in literature", "literature .", "it is", "is not", "not clear", "clear why", "why only", "only this", "this bond", "is cleaved", "as the", "motif occurs", "occurs at", "at several", "several other", "other places", "places in", "the chain.", "chain. mmp14", "a membrane", "membrane associated", "associated mmp", "mmp also", "also known", "known as", "as membrane", "membrane type", "type matrix", "matrix metalloproteinase", "metalloproteinase 1", "mt mmp1", "is able", "to cleave", "cleave collagen", "types i", "ohuchi et", "al. 1997", "1997 .", "collagen fibril diameter", "fibril diameter and", "diameter and spatial", "and spatial organisation", "spatial organisation are", "organisation are dependent", "are dependent on", "dependent on the", "on the species", "species tissue", "tissue type and", "type and stage", "and stage of", "stage of development", "development parry", "parry 1988 .", "1988 . the", ". the lengths", "the lengths of", "lengths of collagen", "of collagen fibrils", "collagen fibrils in", "fibrils in mature", "in mature tissues", "mature tissues are", "tissues are largely", "are largely unknown", "largely unknown but", "unknown but in", "but in tendon", "in tendon can", "tendon can be", "can be measured", "be measured in", "measured in millimetres", "millimetres craig", "craig et al.", "et al. 1989", "al. 1989 .", "1989 . collagen", ". collagen fibrils", "collagen fibrils isolated", "fibrils isolated from", "isolated from adult", "from adult bovine", "adult bovine corneal", "bovine corneal stroma", "corneal stroma had", "stroma had ~350", "had ~350 collagen", "~350 collagen molecules", "collagen molecules in", "molecules in transverse", "in transverse section", "section tapering", "tapering down to", "down to three", "to three molecules", "three molecules at", "molecules at the", "at the growing", "the growing tip", "tip holmes", "holmes & kadler", "& kadler 2005", "kadler 2005 .", "2005 .

the", ".

the classical", "

the classical view", "classical view of", "view of collagenases", "of collagenases is", "collagenases is that", "is that they", "that they actively", "they actively unwind", "actively unwind the", "unwind the triple", "the triple helical", "triple helical chain", "chain a", "a process termed", "process termed molecular", "termed molecular tectonics", "tectonics overall", "2002 bode", "bode & maskos", "& maskos 2003", "before preferentially cleaving", "preferentially cleaving the", "cleaving the alpha2", "the alpha2 chain", "alpha2 chain followed", "chain followed by", "followed by the", "by the remaining", "the remaining chains", "chains chung", "chung et al.", "et al. 2004", "al. 2004 .", "2004 . more", ". more recently", "more recently it", "recently it has", "it has been", "has been suggested", "been suggested that", "suggested that collagen", "that collagen fibrils", "collagen fibrils exist", "fibrils exist in", "exist in an", "in an equilibrium", "an equilibrium between", "equilibrium between protected", "between protected and", "protected and vulnerable", "and vulnerable states", "states stultz", "2002 nerenberg", "nerenberg & stultz", "& stultz 2008", "stultz 2008 .", "2008 . the", ". the prototypical", "the prototypical triple", "prototypical triple helical", "triple helical structure", "helical structure of", "structure of collagen", "of collagen does", "collagen does not", "does not fit", "not fit into", "fit into the", "into the active", "the active site", "active site of", "site of collagenase", "of collagenase mmps.", "collagenase mmps. in", "mmps. in addition", "in addition the", "addition the scissile", "the scissile bonds", "scissile bonds are", "bonds are not", "are not solvent", "not solvent exposed", "solvent exposed and", "exposed and are", "and are therefore", "are therefore inaccessible", "therefore inaccessible to", "inaccessible to the", "to the collagenase", "the collagenase active", "collagenase active site", "site chung", "2004 stultz", "stultz 2002 .", "2002 . it", ". it was", "it was realized", "was realized that", "realized that collagen", "that collagen must", "collagen must locally", "must locally unfold", "locally unfold into", "unfold into non", "into non triple", "non triple helical", "triple helical regions", "helical regions to", "regions to allow", "to allow collagenolysis.", "allow collagenolysis. observations", "collagenolysis. observations using", "observations using circular", "using circular dichroism", "circular dichroism and", "dichroism and differential", "and differential scanning", "differential scanning calorimetry", "scanning calorimetry confirm", "calorimetry confirm that", "confirm that there", "that there is", "there is considerable", "is considerable heterogeneity", "considerable heterogeneity along", "heterogeneity along collagen", "along collagen fibres", "fibres makareeva", "makareeva et al.", "et al. 2008", "2008 allowing", "allowing access for", "access for mmps", "for mmps at", "mmps at physiological", "at physiological temperatures", "temperatures salsas", "salsas escat et", "escat et al.", "et al. 2010", "al. 2010 .

collagen", "2010 .

collagen fibrils", ".

collagen fibrils with", "fibrils with cut", "with cut chains", "cut chains are", "chains are unstable", "are unstable and", "unstable and accessible", "and accessible to", "accessible to proteinases", "to proteinases that", "proteinases that cannot", "that cannot cleave", "cannot cleave intact", "cleave intact collagen", "intact collagen strands", "strands woessner", "woessner & nagase", "& nagase 2000", "2000 somerville", "somerville et al.", "et al. 2003", "al. 2003 .", "2003 . continued", ". continued degradation", "continued degradation leads", "degradation leads to", "leads to the", "to the formation", "the formation of", "formation of gelatin", "gelatin lovejoy", "lovejoy et al.", "et al. 1999", "al. 1999 .", "1999 . degradation", ". degradation of", "degradation of collagen", "of collagen types", "collagen types other", "types other than", "other than i", "than i iii", "i iii is", "iii is less", "is less well", "less well characterized", "well characterized but", "characterized but believed", "but believed to", "believed to occur", "to occur in", "occur in a", "in a similar", "a similar manner.", "similar manner.

metalloproteinases", "

metalloproteinases mmps", "mmps play", "play a major", "a major part", "major part in", "part in the", "in the degradation", "the degradation of", "degradation of several", "of several extracellular", "several extracellular macromolecules", "extracellular macromolecules including", "macromolecules including collagens.", "including collagens. mmp1", "mmp1 welgus", "welgus et al.", "et al. 1981", "mmp8 hasty", "hasty et al.", "et al. 1987", "mmp13 knauper", "knauper et al.", "et al. 1996", "sometimes referred to", "referred to as", "to as collagenases", "as collagenases i", "i ii", "ii and iii", "and iii respectively", "respectively are", "are able to", "able to initiate", "to initiate the", "initiate the intrahelical", "the intrahelical cleavage", "intrahelical cleavage of", "cleavage of the", "of the major", "the major fibril", "major fibril forming", "fibril forming collagens", "forming collagens i", "and iii at", "iii at neutral", "at neutral ph", "ph and", "and thus thought", "thus thought to", "thought to define", "to define the", "define the rate", "the rate limiting", "rate limiting step", "limiting step in", "step in normal", "in normal tissue", "normal tissue remodeling", "tissue remodeling events.", "remodeling events. all", "events. all can", "all can cleave", "can cleave additional", "additional substrates", "substrates including other", "including other collagen", "other collagen subtypes.", "collagen subtypes. collagenases", "subtypes. collagenases cut", "collagenases cut collagen", "cut collagen alpha", "collagen alpha chains", "alpha chains at", "chains at a", "at a single", "a single conserved", "single conserved gly", "conserved gly ile/leu", "gly ile/leu site", "ile/leu site approximately", "site approximately 3/4", "approximately 3/4 of", "3/4 of the", "of the molecule's", "the molecule's length", "molecule's length from", "length from the", "from the n", "the n terminus", "terminus fields", "1991 chung", "2004 . the", ". the cleavage", "the cleavage site", "cleavage site is", "site is characterised", "is characterised by", "characterised by the", "by the motif", "motif g", "i/l a/l", "the g i/l", "g i/l bond", "i/l bond is", "bond is cleaved.", "is cleaved. in", "cleaved. in collagen", "in collagen type", "collagen type i", "type i this", "i this corresponds", "this corresponds to", "corresponds to g953", "to g953 i954", "g953 i954 in", "i954 in the", "in the uniprot", "the uniprot canonical", "uniprot canonical alpha", "canonical alpha chain", "alpha chain sequences", "sequences often", "often given as", "given as g775", "as g775 i776", "g775 i776 in", "i776 in literature", "in literature .", "literature . it", ". it is", "it is not", "is not clear", "not clear why", "clear why only", "why only this", "only this bond", "this bond is", "bond is cleaved", "cleaved as", "as the motif", "the motif occurs", "motif occurs at", "occurs at several", "at several other", "several other places", "other places in", "places in the", "in the chain.", "the chain. mmp14", "mmp14 a", "a membrane associated", "membrane associated mmp", "associated mmp also", "mmp also known", "also known as", "known as membrane", "as membrane type", "membrane type matrix", "type matrix metalloproteinase", "matrix metalloproteinase 1", "1 mt", "is able to", "able to cleave", "to cleave collagen", "cleave collagen types", "collagen types i", "iii ohuchi", "ohuchi et al.", "et al. 1997", "al. 1997 .", "collagen fibril diameter and", "fibril diameter and spatial", "diameter and spatial organisation", "and spatial organisation are", "spatial organisation are dependent", "organisation are dependent on", "are dependent on the", "dependent on the species", "the species tissue", "species tissue type", "tissue type and stage", "type and stage of", "and stage of development", "of development parry", "development parry 1988", "parry 1988 . the", "1988 . the lengths", ". the lengths of", "the lengths of collagen", "lengths of collagen fibrils", "of collagen fibrils in", "collagen fibrils in mature", "fibrils in mature tissues", "in mature tissues are", "mature tissues are largely", "tissues are largely unknown", "are largely unknown but", "largely unknown but in", "unknown but in tendon", "but in tendon can", "in tendon can be", "tendon can be measured", "can be measured in", "be measured in millimetres", "in millimetres craig", "millimetres craig et", "craig et al. 1989", "et al. 1989 .", "al. 1989 . collagen", "1989 . collagen fibrils", ". collagen fibrils isolated", "collagen fibrils isolated from", "fibrils isolated from adult", "isolated from adult bovine", "from adult bovine corneal", "adult bovine corneal stroma", "bovine corneal stroma had", "corneal stroma had ~350", "stroma had ~350 collagen", "had ~350 collagen molecules", "~350 collagen molecules in", "collagen molecules in transverse", "molecules in transverse section", "transverse section tapering", "section tapering down", "tapering down to three", "down to three molecules", "to three molecules at", "three molecules at the", "molecules at the growing", "at the growing tip", "growing tip holmes", "tip holmes &", "holmes & kadler 2005", "& kadler 2005 .", "kadler 2005 .

the", "2005 .

the classical", ".

the classical view", "

the classical view of", "classical view of collagenases", "view of collagenases is", "of collagenases is that", "collagenases is that they", "is that they actively", "that they actively unwind", "they actively unwind the", "actively unwind the triple", "unwind the triple helical", "the triple helical chain", "helical chain a", "chain a process", "a process termed molecular", "process termed molecular tectonics", "molecular tectonics overall", "tectonics overall 2002", "overall 2002 bode", "2002 bode &", "bode & maskos 2003", "2003 before", "before preferentially cleaving the", "preferentially cleaving the alpha2", "cleaving the alpha2 chain", "the alpha2 chain followed", "alpha2 chain followed by", "chain followed by the", "followed by the remaining", "by the remaining chains", "remaining chains chung", "chains chung et", "chung et al. 2004", "et al. 2004 .", "al. 2004 . more", "2004 . more recently", ". more recently it", "more recently it has", "recently it has been", "it has been suggested", "has been suggested that", "been suggested that collagen", "suggested that collagen fibrils", "that collagen fibrils exist", "collagen fibrils exist in", "fibrils exist in an", "exist in an equilibrium", "in an equilibrium between", "an equilibrium between protected", "equilibrium between protected and", "between protected and vulnerable", "protected and vulnerable states", "vulnerable states stultz", "states stultz 2002", "stultz 2002 nerenberg", "2002 nerenberg &", "nerenberg & stultz 2008", "& stultz 2008 .", "stultz 2008 . the", "2008 . the prototypical", ". the prototypical triple", "the prototypical triple helical", "prototypical triple helical structure", "triple helical structure of", "helical structure of collagen", "structure of collagen does", "of collagen does not", "collagen does not fit", "does not fit into", "not fit into the", "fit into the active", "into the active site", "the active site of", "active site of collagenase", "site of collagenase mmps.", "of collagenase mmps. in", "collagenase mmps. in addition", "mmps. in addition the", "in addition the scissile", "addition the scissile bonds", "the scissile bonds are", "scissile bonds are not", "bonds are not solvent", "are not solvent exposed", "not solvent exposed and", "solvent exposed and are", "exposed and are therefore", "and are therefore inaccessible", "are therefore inaccessible to", "therefore inaccessible to the", "inaccessible to the collagenase", "to the collagenase active", "the collagenase active site", "active site chung", "site chung et", "al. 2004 stultz", "2004 stultz 2002", "stultz 2002 . it", "2002 . it was", ". it was realized", "it was realized that", "was realized that collagen", "realized that collagen must", "that collagen must locally", "collagen must locally unfold", "must locally unfold into", "locally unfold into non", "unfold into non triple", "into non triple helical", "non triple helical regions", "triple helical regions to", "helical regions to allow", "regions to allow collagenolysis.", "to allow collagenolysis. observations", "allow collagenolysis. observations using", "collagenolysis. observations using circular", "observations using circular dichroism", "using circular dichroism and", "circular dichroism and differential", "dichroism and differential scanning", "and differential scanning calorimetry", "differential scanning calorimetry confirm", "scanning calorimetry confirm that", "calorimetry confirm that there", "confirm that there is", "that there is considerable", "there is considerable heterogeneity", "is considerable heterogeneity along", "considerable heterogeneity along collagen", "heterogeneity along collagen fibres", "collagen fibres makareeva", "fibres makareeva et", "makareeva et al. 2008", "al. 2008 allowing", "2008 allowing access", "allowing access for mmps", "access for mmps at", "for mmps at physiological", "mmps at physiological temperatures", "physiological temperatures salsas", "temperatures salsas escat", "salsas escat et al.", "escat et al. 2010", "et al. 2010 .

collagen", "al. 2010 .

collagen fibrils", "2010 .

collagen fibrils with", ".

collagen fibrils with cut", "fibrils with cut chains", "with cut chains are", "cut chains are unstable", "chains are unstable and", "are unstable and accessible", "unstable and accessible to", "and accessible to proteinases", "accessible to proteinases that", "to proteinases that cannot", "proteinases that cannot cleave", "that cannot cleave intact", "cannot cleave intact collagen", "cleave intact collagen strands", "collagen strands woessner", "strands woessner &", "woessner & nagase 2000", "nagase 2000 somerville", "2000 somerville et", "somerville et al. 2003", "et al. 2003 .", "al. 2003 . continued", "2003 . continued degradation", ". continued degradation leads", "continued degradation leads to", "degradation leads to the", "leads to the formation", "to the formation of", "the formation of gelatin", "of gelatin lovejoy", "gelatin lovejoy et", "lovejoy et al. 1999", "et al. 1999 .", "al. 1999 . degradation", "1999 . degradation of", ". degradation of collagen", "degradation of collagen types", "of collagen types other", "collagen types other than", "types other than i", "other than i iii", "than i iii is", "i iii is less", "iii is less well", "is less well characterized", "less well characterized but", "well characterized but believed", "characterized but believed to", "but believed to occur", "believed to occur in", "to occur in a", "occur in a similar", "in a similar manner.", "a similar manner.

metalloproteinases", "manner.

metalloproteinases mmps", "mmps play a", "play a major part", "a major part in", "major part in the", "part in the degradation", "in the degradation of", "the degradation of several", "degradation of several extracellular", "of several extracellular macromolecules", "several extracellular macromolecules including", "extracellular macromolecules including collagens.", "macromolecules including collagens. mmp1", "collagens. mmp1 welgus", "mmp1 welgus et", "welgus et al. 1981", "1981 mmp8", "mmp8 hasty et", "hasty et al. 1987", "1987 and", "and mmp13 knauper", "mmp13 knauper et", "knauper et al. 1996", "1996 sometimes", "sometimes referred to as", "referred to as collagenases", "to as collagenases i", "collagenases i ii", "i ii and", "ii and iii respectively", "iii respectively are", "respectively are able", "are able to initiate", "able to initiate the", "to initiate the intrahelical", "initiate the intrahelical cleavage", "the intrahelical cleavage of", "intrahelical cleavage of the", "cleavage of the major", "of the major fibril", "the major fibril forming", "major fibril forming collagens", "fibril forming collagens i", "collagens i ii", "ii and iii at", "and iii at neutral", "iii at neutral ph", "neutral ph and", "ph and thus", "and thus thought to", "thus thought to define", "thought to define the", "to define the rate", "define the rate limiting", "the rate limiting step", "rate limiting step in", "limiting step in normal", "step in normal tissue", "in normal tissue remodeling", "normal tissue remodeling events.", "tissue remodeling events. all", "remodeling events. all can", "events. all can cleave", "all can cleave additional", "cleave additional substrates", "additional substrates including", "substrates including other collagen", "including other collagen subtypes.", "other collagen subtypes. collagenases", "collagen subtypes. collagenases cut", "subtypes. collagenases cut collagen", "collagenases cut collagen alpha", "cut collagen alpha chains", "collagen alpha chains at", "alpha chains at a", "chains at a single", "at a single conserved", "a single conserved gly", "single conserved gly ile/leu", "conserved gly ile/leu site", "gly ile/leu site approximately", "ile/leu site approximately 3/4", "site approximately 3/4 of", "approximately 3/4 of the", "3/4 of the molecule's", "of the molecule's length", "the molecule's length from", "molecule's length from the", "length from the n", "from the n terminus", "n terminus fields", "terminus fields 1991", "fields 1991 chung", "1991 chung et", "al. 2004 . the", "2004 . the cleavage", ". the cleavage site", "the cleavage site is", "cleavage site is characterised", "site is characterised by", "is characterised by the", "characterised by the motif", "the motif g", "motif g i/l", "g i/l a/l", "a/l the", "the g i/l bond", "g i/l bond is", "i/l bond is cleaved.", "bond is cleaved. in", "is cleaved. in collagen", "cleaved. in collagen type", "in collagen type i", "collagen type i this", "type i this corresponds", "i this corresponds to", "this corresponds to g953", "corresponds to g953 i954", "to g953 i954 in", "g953 i954 in the", "i954 in the uniprot", "in the uniprot canonical", "the uniprot canonical alpha", "uniprot canonical alpha chain", "canonical alpha chain sequences", "chain sequences often", "sequences often given", "often given as g775", "given as g775 i776", "as g775 i776 in", "g775 i776 in literature", "i776 in literature .", "in literature . it", "literature . it is", ". it is not", "it is not clear", "is not clear why", "not clear why only", "clear why only this", "why only this bond", "only this bond is", "this bond is cleaved", "is cleaved as", "cleaved as the", "as the motif occurs", "the motif occurs at", "motif occurs at several", "occurs at several other", "at several other places", "several other places in", "other places in the", "places in the chain.", "in the chain. mmp14", "chain. mmp14 a", "mmp14 a membrane", "a membrane associated mmp", "membrane associated mmp also", "associated mmp also known", "mmp also known as", "also known as membrane", "known as membrane type", "as membrane type matrix", "membrane type matrix metalloproteinase", "type matrix metalloproteinase 1", "metalloproteinase 1 mt", "1 mt mmp1", "mmp1 is", "is able to cleave", "able to cleave collagen", "to cleave collagen types", "cleave collagen types i", "types i ii", "and iii ohuchi", "iii ohuchi et", "ohuchi et al. 1997", "et al. 1997 .", "collagen fibril diameter and spatial", "fibril diameter and spatial organisation", "diameter and spatial organisation are", "and spatial organisation are dependent", "spatial organisation are dependent on", "organisation are dependent on the", "are dependent on the species", "on the species tissue", "the species tissue type", "species tissue type and", "tissue type and stage of", "type and stage of development", "stage of development parry", "of development parry 1988", "development parry 1988 .", "parry 1988 . the lengths", "1988 . the lengths of", ". the lengths of collagen", "the lengths of collagen fibrils", "lengths of collagen fibrils in", "of collagen fibrils in mature", "collagen fibrils in mature tissues", "fibrils in mature tissues are", "in mature tissues are largely", "mature tissues are largely unknown", "tissues are largely unknown but", "are largely unknown but in", "largely unknown but in tendon", "unknown but in tendon can", "but in tendon can be", "in tendon can be measured", "tendon can be measured in", "can be measured in millimetres", "measured in millimetres craig", "in millimetres craig et", "millimetres craig et al.", "craig et al. 1989 .", "et al. 1989 . collagen", "al. 1989 . collagen fibrils", "1989 . collagen fibrils isolated", ". collagen fibrils isolated from", "collagen fibrils isolated from adult", "fibrils isolated from adult bovine", "isolated from adult bovine corneal", "from adult bovine corneal stroma", "adult bovine corneal stroma had", "bovine corneal stroma had ~350", "corneal stroma had ~350 collagen", "stroma had ~350 collagen molecules", "had ~350 collagen molecules in", "~350 collagen molecules in transverse", "collagen molecules in transverse section", "in transverse section tapering", "transverse section tapering down", "section tapering down to", "tapering down to three molecules", "down to three molecules at", "to three molecules at the", "three molecules at the growing", "molecules at the growing tip", "the growing tip holmes", "growing tip holmes &", "tip holmes & kadler", "holmes & kadler 2005 .", "& kadler 2005 .

the", "kadler 2005 .

the classical", "2005 .

the classical view", ".

the classical view of", "

the classical view of collagenases", "classical view of collagenases is", "view of collagenases is that", "of collagenases is that they", "collagenases is that they actively", "is that they actively unwind", "that they actively unwind the", "they actively unwind the triple", "actively unwind the triple helical", "unwind the triple helical chain", "triple helical chain a", "helical chain a process", "chain a process termed", "a process termed molecular tectonics", "termed molecular tectonics overall", "molecular tectonics overall 2002", "overall 2002 bode &", "2002 bode & maskos", "maskos 2003 before", "2003 before preferentially", "before preferentially cleaving the alpha2", "preferentially cleaving the alpha2 chain", "cleaving the alpha2 chain followed", "the alpha2 chain followed by", "alpha2 chain followed by the", "chain followed by the remaining", "followed by the remaining chains", "the remaining chains chung", "remaining chains chung et", "chains chung et al.", "chung et al. 2004 .", "et al. 2004 . more", "al. 2004 . more recently", "2004 . more recently it", ". more recently it has", "more recently it has been", "recently it has been suggested", "it has been suggested that", "has been suggested that collagen", "been suggested that collagen fibrils", "suggested that collagen fibrils exist", "that collagen fibrils exist in", "collagen fibrils exist in an", "fibrils exist in an equilibrium", "exist in an equilibrium between", "in an equilibrium between protected", "an equilibrium between protected and", "equilibrium between protected and vulnerable", "between protected and vulnerable states", "and vulnerable states stultz", "vulnerable states stultz 2002", "stultz 2002 nerenberg &", "2002 nerenberg & stultz", "nerenberg & stultz 2008 .", "& stultz 2008 . the", "stultz 2008 . the prototypical", "2008 . the prototypical triple", ". the prototypical triple helical", "the prototypical triple helical structure", "prototypical triple helical structure of", "triple helical structure of collagen", "helical structure of collagen does", "structure of collagen does not", "of collagen does not fit", "collagen does not fit into", "does not fit into the", "not fit into the active", "fit into the active site", "into the active site of", "the active site of collagenase", "active site of collagenase mmps.", "site of collagenase mmps. in", "of collagenase mmps. in addition", "collagenase mmps. in addition the", "mmps. in addition the scissile", "in addition the scissile bonds", "addition the scissile bonds are", "the scissile bonds are not", "scissile bonds are not solvent", "bonds are not solvent exposed", "are not solvent exposed and", "not solvent exposed and are", "solvent exposed and are therefore", "exposed and are therefore inaccessible", "and are therefore inaccessible to", "are therefore inaccessible to the", "therefore inaccessible to the collagenase", "inaccessible to the collagenase active", "to the collagenase active site", "collagenase active site chung", "active site chung et", "site chung et al.", "et al. 2004 stultz", "al. 2004 stultz 2002", "2004 stultz 2002 .", "stultz 2002 . it was", "2002 . it was realized", ". it was realized that", "it was realized that collagen", "was realized that collagen must", "realized that collagen must locally", "that collagen must locally unfold", "collagen must locally unfold into", "must locally unfold into non", "locally unfold into non triple", "unfold into non triple helical", "into non triple helical regions", "non triple helical regions to", "triple helical regions to allow", "helical regions to allow collagenolysis.", "regions to allow collagenolysis. observations", "to allow collagenolysis. observations using", "allow collagenolysis. observations using circular", "collagenolysis. observations using circular dichroism", "observations using circular dichroism and", "using circular dichroism and differential", "circular dichroism and differential scanning", "dichroism and differential scanning calorimetry", "and differential scanning calorimetry confirm", "differential scanning calorimetry confirm that", "scanning calorimetry confirm that there", "calorimetry confirm that there is", "confirm that there is considerable", "that there is considerable heterogeneity", "there is considerable heterogeneity along", "is considerable heterogeneity along collagen", "considerable heterogeneity along collagen fibres", "along collagen fibres makareeva", "collagen fibres makareeva et", "fibres makareeva et al.", "et al. 2008 allowing", "al. 2008 allowing access", "2008 allowing access for", "allowing access for mmps at", "access for mmps at physiological", "for mmps at physiological temperatures", "at physiological temperatures salsas", "physiological temperatures salsas escat", "temperatures salsas escat et", "salsas escat et al. 2010", "escat et al. 2010 .

collagen", "et al. 2010 .

collagen fibrils", "al. 2010 .

collagen fibrils with", "2010 .

collagen fibrils with cut", ".

collagen fibrils with cut chains", "fibrils with cut chains are", "with cut chains are unstable", "cut chains are unstable and", "chains are unstable and accessible", "are unstable and accessible to", "unstable and accessible to proteinases", "and accessible to proteinases that", "accessible to proteinases that cannot", "to proteinases that cannot cleave", "proteinases that cannot cleave intact", "that cannot cleave intact collagen", "cannot cleave intact collagen strands", "intact collagen strands woessner", "collagen strands woessner &", "strands woessner & nagase", "& nagase 2000 somerville", "nagase 2000 somerville et", "2000 somerville et al.", "somerville et al. 2003 .", "et al. 2003 . continued", "al. 2003 . continued degradation", "2003 . continued degradation leads", ". continued degradation leads to", "continued degradation leads to the", "degradation leads to the formation", "leads to the formation of", "to the formation of gelatin", "formation of gelatin lovejoy", "of gelatin lovejoy et", "gelatin lovejoy et al.", "lovejoy et al. 1999 .", "et al. 1999 . degradation", "al. 1999 . degradation of", "1999 . degradation of collagen", ". degradation of collagen types", "degradation of collagen types other", "of collagen types other than", "collagen types other than i", "types other than i iii", "other than i iii is", "than i iii is less", "i iii is less well", "iii is less well characterized", "is less well characterized but", "less well characterized but believed", "well characterized but believed to", "characterized but believed to occur", "but believed to occur in", "believed to occur in a", "to occur in a similar", "occur in a similar manner.", "in a similar manner.

metalloproteinases", "similar manner.

metalloproteinases mmps", "

metalloproteinases mmps play", "mmps play a major", "play a major part in", "a major part in the", "major part in the degradation", "part in the degradation of", "in the degradation of several", "the degradation of several extracellular", "degradation of several extracellular macromolecules", "of several extracellular macromolecules including", "several extracellular macromolecules including collagens.", "extracellular macromolecules including collagens. mmp1", "including collagens. mmp1 welgus", "collagens. mmp1 welgus et", "mmp1 welgus et al.", "al. 1981 mmp8", "mmp8 hasty et al.", "al. 1987 and", "1987 and mmp13", "and mmp13 knauper et", "mmp13 knauper et al.", "al. 1996 sometimes", "1996 sometimes referred", "sometimes referred to as collagenases", "referred to as collagenases i", "as collagenases i ii", "collagenases i ii and", "i ii and iii", "and iii respectively are", "iii respectively are able", "respectively are able to", "are able to initiate the", "able to initiate the intrahelical", "to initiate the intrahelical cleavage", "initiate the intrahelical cleavage of", "the intrahelical cleavage of the", "intrahelical cleavage of the major", "cleavage of the major fibril", "of the major fibril forming", "the major fibril forming collagens", "major fibril forming collagens i", "forming collagens i ii", "collagens i ii and", "ii and iii at neutral", "and iii at neutral ph", "at neutral ph and", "neutral ph and thus", "ph and thus thought", "and thus thought to define", "thus thought to define the", "thought to define the rate", "to define the rate limiting", "define the rate limiting step", "the rate limiting step in", "rate limiting step in normal", "limiting step in normal tissue", "step in normal tissue remodeling", "in normal tissue remodeling events.", "normal tissue remodeling events. all", "tissue remodeling events. all can", "remodeling events. all can cleave", "events. all can cleave additional", "can cleave additional substrates", "cleave additional substrates including", "additional substrates including other", "substrates including other collagen subtypes.", "including other collagen subtypes. collagenases", "other collagen subtypes. collagenases cut", "collagen subtypes. collagenases cut collagen", "subtypes. collagenases cut collagen alpha", "collagenases cut collagen alpha chains", "cut collagen alpha chains at", "collagen alpha chains at a", "alpha chains at a single", "chains at a single conserved", "at a single conserved gly", "a single conserved gly ile/leu", "single conserved gly ile/leu site", "conserved gly ile/leu site approximately", "gly ile/leu site approximately 3/4", "ile/leu site approximately 3/4 of", "site approximately 3/4 of the", "approximately 3/4 of the molecule's", "3/4 of the molecule's length", "of the molecule's length from", "the molecule's length from the", "molecule's length from the n", "length from the n terminus", "the n terminus fields", "n terminus fields 1991", "fields 1991 chung et", "1991 chung et al.", "et al. 2004 . the", "al. 2004 . the cleavage", "2004 . the cleavage site", ". the cleavage site is", "the cleavage site is characterised", "cleavage site is characterised by", "site is characterised by the", "is characterised by the motif", "by the motif g", "the motif g i/l", "a/l the g", "the g i/l bond is", "g i/l bond is cleaved.", "i/l bond is cleaved. in", "bond is cleaved. in collagen", "is cleaved. in collagen type", "cleaved. in collagen type i", "in collagen type i this", "collagen type i this corresponds", "type i this corresponds to", "i this corresponds to g953", "this corresponds to g953 i954", "corresponds to g953 i954 in", "to g953 i954 in the", "g953 i954 in the uniprot", "i954 in the uniprot canonical", "in the uniprot canonical alpha", "the uniprot canonical alpha chain", "uniprot canonical alpha chain sequences", "alpha chain sequences often", "chain sequences often given", "sequences often given as", "often given as g775 i776", "given as g775 i776 in", "as g775 i776 in literature", "g775 i776 in literature .", "i776 in literature . it", "in literature . it is", "literature . it is not", ". it is not clear", "it is not clear why", "is not clear why only", "not clear why only this", "clear why only this bond", "why only this bond is", "only this bond is cleaved", "bond is cleaved as", "is cleaved as the", "cleaved as the motif", "as the motif occurs at", "the motif occurs at several", "motif occurs at several other", "occurs at several other places", "at several other places in", "several other places in the", "other places in the chain.", "places in the chain. mmp14", "the chain. mmp14 a", "chain. mmp14 a membrane", "mmp14 a membrane associated", "a membrane associated mmp also", "membrane associated mmp also known", "associated mmp also known as", "mmp also known as membrane", "also known as membrane type", "known as membrane type matrix", "as membrane type matrix metalloproteinase", "membrane type matrix metalloproteinase 1", "matrix metalloproteinase 1 mt", "metalloproteinase 1 mt mmp1", "mt mmp1 is", "mmp1 is able", "is able to cleave collagen", "able to cleave collagen types", "to cleave collagen types i", "collagen types i ii", "types i ii and", "ii and iii ohuchi", "and iii ohuchi et", "iii ohuchi et al.", "ohuchi et al. 1997 ." ] }, { "record_id": "GLY_000594_1_56", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1445148", "r hsa", "hsa 1445148", "r hsa 1445148" ] }, { "record_id": "GLY_000594_1_56", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translocation of", "of slc2a4", "to the", "the plasma", "plasma membrane", "translocation of slc2a4", "slc2a4 glut4", "glut4 to", "to the plasma", "the plasma membrane", "of slc2a4 glut4", "glut4 to the", "to the plasma membrane", "translocation of slc2a4 glut4", "slc2a4 glut4 to", "glut4 to the plasma", "in adipocytes", "adipocytes and", "and 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myosins", "and activation of myosins.
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many beta", "defensins show", "show expression", "expression that", "that correlates", "correlates with", "with infection", "sahl et", "et al.", "al. 2005", "pazgier et", "al. 2006", "2006 .", ". all", "all so", "so far", "far characterized", "characterized beta", "i.e. beta", "defensin 1", "and 128", "have antimicrobial", "antimicrobial properties", ". for", "for beta", "defensins 4a", "103 and", "and 118", "and 18", "this has", "has been", "been shown", "shown to", "to correlate", "correlate with", "with membrane", "membrane permeabilization", "permeabilization effects", "antcheva et", "al. 2004", "yenugu et", "2004 .", ". electrostatic", "electrostatic interaction", "interaction and", "and disruption", "disruption of", "of microbial", "microbial membranes", "membranes is", "is widely", "widely believed", "believed to", "to the", "the primary", "primary mechanism", "mechanism of", "of action", "action for", "beta defensins.", "defensins. two", "two models", "models explain", "explain how", "how membrane", "membrane disruption", "disruption takes", "takes place", "the 'pore", "'pore model'", "model' which", "which postulates", "postulates that", "that beta", "defensins form", "form transmembrane", "transmembrane pores", "pores in", "in a", "a similar", "similar manner", "manner to", "to alpha", "alpha defensins", "and the", "the 'carpet", "'carpet model'", "which suggests", "suggests that", "defensins act", "act as", "as detergents.", "detergents. beta", "defensins contain", "contain 6", "6 conserved", "conserved cysteine", "cysteine residues", "residues that", "that in", "in beta", "defensins 1", "4a and", "and 103", "hbd1 3", "are experimentally", "experimentally confirmed", "confirmed to", "to be", "be cross", "cross linked", "linked 1", "1 5", "2 4", "3 6.", "6. the", "the canonical", "canonical sequence", "sequence for", "defensins is", "is x2", "x2 10cx5", "10cx5 6", "6 g/a", "g/a xcx3", "xcx3 4cx9", "4cx9 13cx4", "13cx4 7ccxn.", "7ccxn. structurally", "structurally they", "they are", "are similar", "similar to", "defensins but", "but with", "with much", "much shorter", "shorter pre", "pre regions.", "regions. though", "though dimerization", "dimerization of", "of some", "some beta", "defensins has", "been reported", "reported this", "this is", "is not", "not the", "the case", "case for", "for all", "all and", "and it", "it is", "is unclear", "unclear whether", "whether it", "is required", "required for", "for function.", "function. the", "the majority", "majority of", "of functional", "functional studies", "studies have", "have focused", "focused on", "on beta", "defensin 103", "which has", "has the", "the most", "most significant", "significant antimicrobial", "antimicrobial activity", "activity at", "at physiological", "physiological salt", "salt concentrations", "harder et", "al. 2001", "2001 .", ". beta", "is highly", "highly cationic", "cationic with", "with a", "a net", "net charge", "charge of", "of +11", "+11 e0.", "it exhibits", "exhibits broad", "broad spectrum", "spectrum antimicrobial", "activity against", "against gram", "gram positive", "positive bacteria", "bacteria and", "and some", "some gram", "gram negative", "negative bacteria", "though some", "some species", "species are", "are highly", "highly resistant", "sahly et", "al. 2003", "2003 .", ". sensitivity", "sensitivity correlates", "with lipid", "lipid composition", "composition of", "of the", "the membrane", "with more", "more negatively", "negatively charged", "charged lipids", "lipids correlating", "correlating with", "with larger", "larger beta", "103 induced", "induced changes", "changes in", "in membrane", "membrane capacitance", "bohling et", ". though", "though membrane", "disruption is", "be the", "action of", "of beta", "defensins they", "they have", "have other", "other antimicrobial", "such as", "as inhibition", "inhibition of", "of cell", "cell wall", "wall biosynthesis", "sass et", "al. 2010", "and chemoattractant", "chemoattractant effects", "yang et", "al. 1999", "niyonsaba et", "al. 2002", ". the", "the chemotactic", "chemotactic activity", "activity of", "for memory", "memory t", "t cells", "cells and", "and immature", "immature dcs", "dcs is", "is mediated", "mediated through", "through binding", "binding to", "the chemokine", "chemokine receptor", "receptor ccr6", "ccr6 and", "and probably", "probably another", "another unidentified", "unidentified gi", "gi coupled", "coupled receptor", "2000 .", ".
", "

like", "
like defensins", "the human", "human cathelicidin", "cathelicidin ll37", "ll37 peptide", "peptide is", "is rich", "rich in", "in positively", "positively charged", "lehrer &", "& ganz", "ganz 2002", "2002 .
expression", ".
expression of", "of certain", "certain beta", "defensins can", "can be", "be induced", "induced in", "in response", "response to", "to various", "various signals", "as bacteria", "pathogen associated", "associated molecular", "molecular patterns", "or proinflammatory", "proinflammatory cytokines", "ganz 2003", ". like", "like the", "the alpha", "copy number", "number variation", "variation has", "reported for", "for defb4", "defb103 and", "and defb104", "defb104 with", "with individuals", "individuals having", "having 2", "2 12", "12 copies", "copies per", "per diploid", "diploid genome.", "genome. in", "in contrast", "contrast defb1", "defb1 does", "does not", "not show", "show such", "such variation", "variation but", "but exhibits", "exhibits a", "a number", "number of", "of snps", "hollox et", "linzmier &", "ganz 2005", "2005 .", "humans have 38", "have 38 beta", "38 beta defensin", "beta defensin genes", "defensin genes plus", "genes plus 9", "plus 9 10", "9 10 pseudogenes", "pseudogenes details", "details available on", "available on the", "on the hgnc", "the hgnc website", "hgnc website at", "website at http://www.genenames.org/genefamilies/defb", "at http://www.genenames.org/genefamilies/defb .", "http://www.genenames.org/genefamilies/defb . many", ". many beta", "many beta defensins", "beta defensins are", "defensins are encoded", "are encoded by", "encoded by recently", "by recently duplicated", "recently duplicated genes", "duplicated genes giving", "genes giving rise", "giving rise to", "rise to identical", "to identical transcripts.", "identical transcripts. nomenclature", "transcripts. nomenclature is", "nomenclature is confusing", "is confusing and", "confusing and currently", "and currently in", "currently in transition.", "in transition. uniprot", "transition. uniprot recommended", "uniprot recommended names", "recommended names are", "names are used", "are used throughout", "used throughout this", "throughout this pathway.
many", "this pathway.
many beta", "pathway.
many beta defensins", "beta defensins show", "defensins show expression", "show expression that", "expression that correlates", "that correlates with", "correlates with infection", "infection sahl", "sahl et al.", "et al. 2005", "2005 pazgier", "pazgier et al.", "et al. 2006", "al. 2006 .", "2006 . all", ". all so", "all so far", "so far characterized", "far characterized beta", "characterized beta defensins", "defensins i.e.", "i.e. beta defensin", "beta defensin 1", "1 hbd1", "4a hbd2", "103 hbd3", "104 hbd4", "106 hbd6", "118 hbd18", "hbd18 and", "128 hbd28", "hbd28 have", "have antimicrobial properties", "properties pazgier", "2006 . for", ". for beta", "for beta defensins", "beta defensins 4a", "4a 103", "103 and 118", "118 hbd2", "hbd2 3", "3 and", "18 this", "this has been", "has been shown", "been shown to", "shown to correlate", "to correlate with", "correlate with membrane", "with membrane permeabilization", "membrane permeabilization effects", "effects antcheva", "antcheva et al.", "et al. 2004", "2004 sahl", "2005 yenugu", "yenugu et al.", "al. 2004 .", "2004 . electrostatic", ". electrostatic interaction", "electrostatic interaction and", "interaction and disruption", "and disruption of", "disruption of microbial", "of microbial membranes", "microbial membranes is", "membranes is widely", "is widely believed", "widely believed to", "believed to the", "to the primary", "the primary mechanism", "primary mechanism of", "mechanism of action", "of action for", "action for beta", "for beta defensins.", "beta defensins. two", "defensins. two models", "two models explain", "models explain how", "explain how membrane", "how membrane disruption", "membrane disruption takes", "disruption takes place", "place the", "the 'pore model'", "'pore model' which", "model' which postulates", "which postulates that", "postulates that beta", "that beta defensins", "beta defensins form", "defensins form transmembrane", "form transmembrane pores", "transmembrane pores in", "pores in a", "in a similar", "a similar manner", "similar manner to", "manner to alpha", "to alpha defensins", "defensins and", "and the 'carpet", "the 'carpet model'", "which suggests that", "suggests that beta", "beta defensins act", "defensins act as", "act as detergents.", "as detergents. beta", "detergents. beta defensins", "beta defensins contain", "defensins contain 6", "contain 6 conserved", "6 conserved cysteine", "conserved cysteine residues", "cysteine residues that", "residues that in", "that in beta", "in beta defensins", "beta defensins 1", "1 4a", "4a and 103", "103 hbd1", "3 are", "are experimentally confirmed", "experimentally confirmed to", "confirmed to be", "to be cross", "be cross linked", "cross linked 1", "linked 1 5", "5 2", "4 3", "3 6. the", "6. the canonical", "the canonical sequence", "canonical sequence for", "sequence for beta", "beta defensins is", "defensins is x2", "is x2 10cx5", "x2 10cx5 6", "10cx5 6 g/a", "6 g/a xcx3", "g/a xcx3 4cx9", "xcx3 4cx9 13cx4", "4cx9 13cx4 7ccxn.", "13cx4 7ccxn. structurally", "7ccxn. structurally they", "structurally they are", "they are similar", "are similar to", "similar to alpha", "alpha defensins but", "defensins but with", "but with much", "with much shorter", "much shorter pre", "shorter pre regions.", "pre regions. though", "regions. though dimerization", "though dimerization of", "dimerization of some", "of some beta", "some beta defensins", "beta defensins has", "defensins has been", "has been reported", "been reported this", "reported this is", "this is not", "is not the", "not the case", "the case for", "case for all", "for all and", "all and it", "and it is", "it is unclear", "is unclear whether", "unclear whether it", "whether it is", "it is required", "is required for", "required for function.", "for function. the", "function. the majority", "the majority of", "majority of functional", "of functional studies", "functional studies have", "studies have focused", "have focused on", "focused on beta", "on beta defensin", "beta defensin 103", "which has the", "has the most", "the most significant", "most significant antimicrobial", "significant antimicrobial activity", "antimicrobial activity at", "activity at physiological", "at physiological salt", "physiological salt concentrations", "concentrations harder", "harder et al.", "et al. 2001", "al. 2001 .", "2001 . beta", ". beta defensin", "103 is", "is highly cationic", "highly cationic with", "cationic with a", "with a net", "a net charge", "net charge of", "charge of +11", "of +11 e0.", "e0. it", "it exhibits broad", "exhibits broad spectrum", "broad spectrum antimicrobial", "spectrum antimicrobial activity", "antimicrobial activity against", "activity against gram", "against gram positive", "gram positive bacteria", "positive bacteria and", "bacteria and some", "and some gram", "some gram negative", "gram negative bacteria", "bacteria harder", "though some species", "some species are", "species are highly", "are highly resistant", "resistant sahly", "sahly et al.", "et al. 2003", "al. 2003 .", "2003 . sensitivity", ". sensitivity correlates", "sensitivity correlates with", "correlates with lipid", "with lipid composition", "lipid composition of", "composition of the", "of the membrane", "membrane with", "with more negatively", "more negatively charged", "negatively charged lipids", "charged lipids correlating", "lipids correlating with", "correlating with larger", "with larger beta", "larger beta defensin", "defensin 103 induced", "103 induced changes", "induced changes in", "changes in membrane", "in membrane capacitance", "capacitance bohling", "bohling et al.", "2006 . though", ". though membrane", "though membrane disruption", "membrane disruption is", "disruption is widely", "believed to be", "to be the", "be the primary", "of action of", "action of beta", "of beta defensins", "beta defensins they", "defensins they have", "they have other", "have other antimicrobial", "other antimicrobial properties", "properties such", "such as inhibition", "as inhibition of", "inhibition of cell", "of cell wall", "cell wall biosynthesis", "biosynthesis sass", "sass et al.", "et al. 2010", "and chemoattractant effects", "effects yang", "yang et al.", "et al. 1999", "1999 niyonsaba", "niyonsaba et al.", "et al. 2002", "2002 2004", "2004 . the", ". the chemotactic", "the chemotactic activity", "chemotactic activity of", "activity of beta", "3 for", "for memory t", "memory t cells", "t cells and", "cells and immature", "and immature dcs", "immature dcs is", "dcs is mediated", "is mediated through", "mediated through binding", "through binding to", "binding to the", "to the chemokine", "the chemokine receptor", "chemokine receptor ccr6", "receptor ccr6 and", "ccr6 and probably", "and probably another", "probably another unidentified", "another unidentified gi", "unidentified gi coupled", "gi coupled receptor", "receptor yang", "1999 2000", "2000 .
", ".

like", "

like defensins", "defensins the", "the human cathelicidin", "human cathelicidin ll37", "cathelicidin ll37 peptide", "ll37 peptide is", "peptide is rich", "is rich in", "rich in positively", "in positively charged", "charged residues", "residues lehrer", "lehrer & ganz", "& ganz 2002", "ganz 2002 .
expression", "2002 .
expression of", ".
expression of certain", "of certain beta", "certain beta defensins", "beta defensins can", "defensins can be", "can be induced", "be induced in", "induced in response", "in response to", "response to various", "to various signals", "signals such", "such as bacteria", "bacteria pathogen", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "or proinflammatory cytokines", "cytokines ganz", "2003 yang", "2004 . like", ". like the", "like the alpha", "the alpha defensins", "defensins copy", "copy number variation", "number variation has", "variation has been", "been reported for", "reported for defb4", "defb4 defb103", "defb103 and defb104", "and defb104 with", "defb104 with individuals", "with individuals having", "individuals having 2", "having 2 12", "2 12 copies", "12 copies per", "copies per diploid", "per diploid genome.", "diploid genome. in", "genome. in contrast", "in contrast defb1", "contrast defb1 does", "defb1 does not", "does not show", "not show such", "show such variation", "such variation but", "variation but exhibits", "but exhibits a", "exhibits a number", "a number of", "number of snps", "snps hollox", "hollox et al.", "2003 linzmier", "linzmier & ganz", "& ganz 2005", "ganz 2005 .", "humans have 38 beta", "have 38 beta defensin", "38 beta defensin genes", "beta defensin genes plus", "defensin genes plus 9", "genes plus 9 10", "plus 9 10 pseudogenes", "10 pseudogenes details", "pseudogenes details available", "details available on the", "available on the hgnc", "on the hgnc website", "the hgnc website at", "hgnc website at http://www.genenames.org/genefamilies/defb", "website at http://www.genenames.org/genefamilies/defb .", "at http://www.genenames.org/genefamilies/defb . many", "http://www.genenames.org/genefamilies/defb . many beta", ". many beta defensins", "many beta defensins are", "beta defensins are encoded", "defensins are encoded by", "are encoded by recently", "encoded by recently duplicated", "by recently duplicated genes", "recently duplicated genes giving", "duplicated genes giving rise", "genes giving rise to", "giving rise to identical", "rise to identical transcripts.", "to identical transcripts. nomenclature", "identical transcripts. nomenclature is", "transcripts. nomenclature is confusing", "nomenclature is confusing and", "is confusing and currently", "confusing and currently in", "and currently in transition.", "currently in transition. uniprot", "in transition. uniprot recommended", "transition. uniprot recommended names", "uniprot recommended names are", "recommended names are used", "names are used throughout", "are used throughout this", "used throughout this pathway.
many", "throughout this pathway.
many beta", "this pathway.
many beta defensins", "pathway.
many beta defensins show", "beta defensins show expression", "defensins show expression that", "show expression that correlates", "expression that correlates with", "that correlates with infection", "with infection sahl", "infection sahl et", "sahl et al. 2005", "al. 2005 pazgier", "2005 pazgier et", "pazgier et al. 2006", "et al. 2006 .", "al. 2006 . all", "2006 . all so", ". all so far", "all so far characterized", "so far characterized beta", "far characterized beta defensins", "beta defensins i.e.", "defensins i.e. beta", "i.e. beta defensin 1", "defensin 1 hbd1", "hbd1 4a", "hbd2 103", "hbd3 104", "hbd4 106", "hbd6 118", "hbd18 and 128", "and 128 hbd28", "hbd28 have antimicrobial", "antimicrobial properties pazgier", "properties pazgier et", "al. 2006 . for", "2006 . for beta", ". for beta defensins", "for beta defensins 4a", "defensins 4a 103", "4a 103 and", "and 118 hbd2", "3 and 18", "and 18 this", "18 this has", "this has been shown", "has been shown to", "been shown to correlate", "shown to correlate with", "to correlate with membrane", "correlate with membrane permeabilization", "with membrane permeabilization effects", "permeabilization effects antcheva", "effects antcheva et", "antcheva et al. 2004", "al. 2004 sahl", "2004 sahl et", "al. 2005 yenugu", "2005 yenugu et", "yenugu et al. 2004", "et al. 2004 .", "al. 2004 . electrostatic", "2004 . electrostatic interaction", ". electrostatic interaction and", "electrostatic interaction and disruption", "interaction and disruption of", "and disruption of microbial", "disruption of microbial membranes", "of microbial membranes is", "microbial membranes is widely", "membranes is widely believed", "is widely believed to", "widely believed to the", "believed to the primary", "to the primary mechanism", "the primary mechanism of", "primary mechanism of action", "mechanism of action for", "of action for beta", "action for beta defensins.", "for beta defensins. two", "beta defensins. two models", "defensins. two models explain", "two models explain how", "models explain how membrane", "explain how membrane disruption", "how membrane disruption takes", "membrane disruption takes place", "takes place the", "place the 'pore", "the 'pore model' which", "'pore model' which postulates", "model' which postulates that", "which postulates that beta", "postulates that beta defensins", "that beta defensins form", "beta defensins form transmembrane", "defensins form transmembrane pores", "form transmembrane pores in", "transmembrane pores in a", "pores in a similar", "in a similar manner", "a similar manner to", "similar manner to alpha", "manner to alpha defensins", "alpha defensins and", "defensins and the", "and the 'carpet model'", "'carpet model' which", "model' which suggests", "which suggests that beta", "suggests that beta defensins", "that beta defensins act", "beta defensins act as", "defensins act as detergents.", "act as detergents. beta", "as detergents. beta defensins", "detergents. beta defensins contain", "beta defensins contain 6", "defensins contain 6 conserved", "contain 6 conserved cysteine", "6 conserved cysteine residues", "conserved cysteine residues that", "cysteine residues that in", "residues that in beta", "that in beta defensins", "in beta defensins 1", "defensins 1 4a", "1 4a and", "and 103 hbd1", "103 hbd1 3", "hbd1 3 are", "3 are experimentally", "are experimentally confirmed to", "experimentally confirmed to be", "confirmed to be cross", "to be cross linked", "be cross linked 1", "cross linked 1 5", "1 5 2", "5 2 4", "2 4 3", "4 3 6.", "3 6. the canonical", "6. the canonical sequence", "the canonical sequence for", "canonical sequence for beta", "sequence for beta defensins", "for beta defensins is", "beta defensins is x2", "defensins is x2 10cx5", "is x2 10cx5 6", "x2 10cx5 6 g/a", "10cx5 6 g/a xcx3", "6 g/a xcx3 4cx9", "g/a xcx3 4cx9 13cx4", "xcx3 4cx9 13cx4 7ccxn.", "4cx9 13cx4 7ccxn. structurally", "13cx4 7ccxn. structurally they", "7ccxn. structurally they are", "structurally they are similar", "they are similar to", "are similar to alpha", "similar to alpha defensins", "to alpha defensins but", "alpha defensins but with", "defensins but with much", "but with much shorter", "with much shorter pre", "much shorter pre regions.", "shorter pre regions. though", "pre regions. though dimerization", "regions. though dimerization of", "though dimerization of some", "dimerization of some beta", "of some beta defensins", "some beta defensins has", "beta defensins has been", "defensins has been reported", "has been reported this", "been reported this is", "reported this is not", "this is not the", "is not the case", "not the case for", "the case for all", "case for all and", "for all and it", "all and it is", "and it is unclear", "it is unclear whether", "is unclear whether it", "unclear whether it is", "whether it is required", "it is required for", "is required for function.", "required for function. the", "for function. the majority", "function. the majority of", "the majority of functional", "majority of functional studies", "of functional studies have", "functional studies have focused", "studies have focused on", "have focused on beta", "focused on beta defensin", "on beta defensin 103", "defensin 103 hbd3", "hbd3 which", "which has the most", "has the most significant", "the most significant antimicrobial", "most significant antimicrobial activity", "significant antimicrobial activity at", "antimicrobial activity at physiological", "activity at physiological salt", "at physiological salt concentrations", "salt concentrations harder", "concentrations harder et", "harder et al. 2001", "et al. 2001 .", "al. 2001 . beta", "2001 . beta defensin", ". beta defensin 103", "defensin 103 is", "103 is highly", "is highly cationic with", "highly cationic with a", "cationic with a net", "with a net charge", "a net charge of", "net charge of +11", "charge of +11 e0.", "+11 e0. it", "e0. it exhibits", "it exhibits broad spectrum", "exhibits broad spectrum antimicrobial", "broad spectrum antimicrobial activity", "spectrum antimicrobial activity against", "antimicrobial activity against gram", "activity against gram positive", "against gram positive bacteria", "gram positive bacteria and", "positive bacteria and some", "bacteria and some gram", "and some gram negative", "some gram negative bacteria", "negative bacteria harder", "bacteria harder et", "2001 though", "though some species are", "some species are highly", "species are highly resistant", "highly resistant sahly", "resistant sahly et", "sahly et al. 2003", "et al. 2003 .", "al. 2003 . sensitivity", "2003 . sensitivity correlates", ". sensitivity correlates with", "sensitivity correlates with lipid", "correlates with lipid composition", "with lipid composition of", "lipid composition of the", "composition of the membrane", "the membrane with", "membrane with more", "with more negatively charged", "more negatively charged lipids", "negatively charged lipids correlating", "charged lipids correlating with", "lipids correlating with larger", "correlating with larger beta", "with larger beta defensin", "larger beta defensin 103", "beta defensin 103 induced", "defensin 103 induced changes", "103 induced changes in", "induced changes in membrane", "changes in membrane capacitance", "membrane capacitance bohling", "capacitance bohling et", "bohling et al. 2006", "al. 2006 . though", "2006 . though membrane", ". though membrane disruption", "though membrane disruption is", "membrane disruption is widely", "disruption is widely believed", "widely believed to be", "believed to be the", "to be the primary", "be the primary mechanism", "mechanism of action of", "of action of beta", "action of beta defensins", "of beta defensins they", "beta defensins they have", "defensins they have other", "they have other antimicrobial", "have other antimicrobial properties", "antimicrobial properties such", "properties such as", "such as inhibition of", "as inhibition of cell", "inhibition of cell wall", "of cell wall biosynthesis", "wall biosynthesis sass", "biosynthesis sass et", "sass et al. 2010", "2010 and", "chemoattractant effects yang", "effects yang et", "yang et al. 1999", "al. 1999 niyonsaba", "1999 niyonsaba et", "niyonsaba et al. 2002", "al. 2002 2004", "2002 2004 .", "2004 . the chemotactic", ". the chemotactic activity", "the chemotactic activity of", "chemotactic activity of beta", "activity of beta defensins", "of beta defensins 1", "hbd1 3 for", "3 for memory", "for memory t cells", "memory t cells and", "t cells and immature", "cells and immature dcs", "and immature dcs is", "immature dcs is mediated", "dcs is mediated through", "is mediated through binding", "mediated through binding to", "through binding to the", "binding to the chemokine", "to the chemokine receptor", "the chemokine receptor ccr6", "chemokine receptor ccr6 and", "receptor ccr6 and probably", "ccr6 and probably another", "and probably another unidentified", "probably another unidentified gi", "another unidentified gi coupled", "unidentified gi coupled receptor", "coupled receptor yang", "receptor yang et", "al. 1999 2000", "1999 2000 .", "2000 .

like", ".

like defensins", "
like defensins the", "defensins the human", "the human cathelicidin ll37", "human cathelicidin ll37 peptide", "cathelicidin ll37 peptide is", "ll37 peptide is rich", "peptide is rich in", "is rich in positively", "rich in positively charged", "positively charged residues", "residues lehrer &", "lehrer & ganz 2002", "& ganz 2002 .
expression", "ganz 2002 .
expression of", "2002 .
expression of certain", ".
expression of certain beta", "of certain beta defensins", "certain beta defensins can", "beta defensins can be", "defensins can be induced", "can be induced in", "be induced in response", "induced in response to", "in response to various", "response to various signals", "various signals such", "signals such as", "as bacteria pathogen", "bacteria pathogen associated", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps or", "proinflammatory cytokines ganz", "cytokines ganz 2003", "ganz 2003 yang", "2003 yang et", "yang et al. 2004", "al. 2004 . like", "2004 . like the", ". like the alpha", "like the alpha defensins", "alpha defensins copy", "defensins copy number", "copy number variation has", "number variation has been", "variation has been reported", "has been reported for", "been reported for defb4", "for defb4 defb103", "defb4 defb103 and", "defb103 and defb104 with", "and defb104 with individuals", "defb104 with individuals having", "with individuals having 2", "individuals having 2 12", "having 2 12 copies", "2 12 copies per", "12 copies per diploid", "copies per diploid genome.", "per diploid genome. in", "diploid genome. in contrast", "genome. in contrast defb1", "in contrast defb1 does", "contrast defb1 does not", "defb1 does not show", "does not show such", "not show such variation", "show such variation but", "such variation but exhibits", "variation but exhibits a", "but exhibits a number", "exhibits a number of", "a number of snps", "of snps hollox", "snps hollox et", "hollox et al. 2003", "al. 2003 linzmier", "2003 linzmier &", "linzmier & ganz 2005", "& ganz 2005 .", "humans have 38 beta defensin", "have 38 beta defensin genes", "38 beta defensin genes plus", "beta defensin genes plus 9", "defensin genes plus 9 10", "genes plus 9 10 pseudogenes", "9 10 pseudogenes details", "10 pseudogenes details available", "pseudogenes details available on", "details available on the hgnc", "available on the hgnc website", "on the hgnc website at", "the hgnc website at http://www.genenames.org/genefamilies/defb", "hgnc website at http://www.genenames.org/genefamilies/defb .", "website at http://www.genenames.org/genefamilies/defb . many", "at http://www.genenames.org/genefamilies/defb . many beta", "http://www.genenames.org/genefamilies/defb . many beta defensins", ". many beta defensins are", "many beta defensins are encoded", "beta defensins are encoded by", "defensins are encoded by recently", "are encoded by recently duplicated", "encoded by recently duplicated genes", "by recently duplicated genes giving", "recently duplicated genes giving rise", "duplicated genes giving rise to", "genes giving rise to identical", "giving rise to identical transcripts.", "rise to identical transcripts. nomenclature", "to identical transcripts. nomenclature is", "identical transcripts. nomenclature is confusing", "transcripts. nomenclature is confusing and", "nomenclature is confusing and currently", "is confusing and currently in", "confusing and currently in transition.", "and currently in transition. uniprot", "currently in transition. uniprot recommended", "in transition. uniprot recommended names", "transition. uniprot recommended names are", "uniprot recommended names are used", "recommended names are used throughout", "names are used throughout this", "are used throughout this pathway.
many", "used throughout this pathway.
many beta", "throughout this pathway.
many beta defensins", "this pathway.
many beta defensins show", "pathway.
many beta defensins show expression", "beta defensins show expression that", "defensins show expression that correlates", "show expression that correlates with", "expression that correlates with infection", "correlates with infection sahl", "with infection sahl et", "infection sahl et al.", "et al. 2005 pazgier", "al. 2005 pazgier et", "2005 pazgier et al.", "pazgier et al. 2006 .", "et al. 2006 . all", "al. 2006 . all so", "2006 . all so far", ". all so far characterized", "all so far characterized beta", "so far characterized beta defensins", "characterized beta defensins i.e.", "beta defensins i.e. beta", "defensins i.e. beta defensin", "beta defensin 1 hbd1", "118 hbd18 and", "128 hbd28 have", "hbd28 have antimicrobial properties", "have antimicrobial properties pazgier", "antimicrobial properties pazgier et", "properties pazgier et al.", "et al. 2006 . for", "al. 2006 . for beta", "2006 . for beta defensins", ". for beta defensins 4a", "beta defensins 4a 103", "defensins 4a 103 and", "4a 103 and 118", "103 and 118 hbd2", "118 hbd2 3", "hbd2 3 and", "and 18 this has", "18 this has been", "this has been shown to", "has been shown to correlate", "been shown to correlate with", "shown to correlate with membrane", "to correlate with membrane permeabilization", "correlate with membrane permeabilization effects", "membrane permeabilization effects antcheva", "permeabilization effects antcheva et", "effects antcheva et al.", "et al. 2004 sahl", "al. 2004 sahl et", "2004 sahl et al.", "et al. 2005 yenugu", "al. 2005 yenugu et", "2005 yenugu et al.", "yenugu et al. 2004 .", "et al. 2004 . electrostatic", "al. 2004 . electrostatic interaction", "2004 . electrostatic interaction and", ". electrostatic interaction and disruption", "electrostatic interaction and disruption of", "interaction and disruption of microbial", "and disruption of microbial membranes", "disruption of microbial membranes is", "of microbial membranes is widely", "microbial membranes is widely believed", "membranes is widely believed to", "is widely believed to the", "widely believed to the primary", "believed to the primary mechanism", "to the primary mechanism of", "the primary mechanism of action", "primary mechanism of action for", "mechanism of action for beta", "of action for beta defensins.", "action for beta defensins. two", "for beta defensins. two models", "beta defensins. two models explain", "defensins. two models explain how", "two models explain how membrane", "models explain how membrane disruption", "explain how membrane disruption takes", "how membrane disruption takes place", "disruption takes place the", "takes place the 'pore", "place the 'pore model'", "the 'pore model' which postulates", "'pore model' which postulates that", "model' which postulates that beta", "which postulates that beta defensins", "postulates that beta defensins form", "that beta defensins form transmembrane", "beta defensins form transmembrane pores", "defensins form transmembrane pores in", "form transmembrane pores in a", "transmembrane pores in a similar", "pores in a similar manner", "in a similar manner to", "a similar manner to alpha", "similar manner to alpha defensins", "to alpha defensins and", "alpha defensins and the", "defensins and the 'carpet", "the 'carpet model' which", "'carpet model' which suggests", "model' which suggests that", "which suggests that beta defensins", "suggests that beta defensins act", "that beta defensins act as", "beta defensins act as detergents.", "defensins act as detergents. beta", "act as detergents. beta defensins", "as detergents. beta defensins contain", "detergents. beta defensins contain 6", "beta defensins contain 6 conserved", "defensins contain 6 conserved cysteine", "contain 6 conserved cysteine residues", "6 conserved cysteine residues that", "conserved cysteine residues that in", "cysteine residues that in beta", "residues that in beta defensins", "that in beta defensins 1", "beta defensins 1 4a", "defensins 1 4a and", "1 4a and 103", "4a and 103 hbd1", "and 103 hbd1 3", "hbd1 3 are experimentally", "3 are experimentally confirmed", "are experimentally confirmed to be", "experimentally confirmed to be cross", "confirmed to be cross linked", "to be cross linked 1", "be cross linked 1 5", "linked 1 5 2", "1 5 2 4", "2 4 3 6.", "4 3 6. the", "3 6. the canonical sequence", "6. the canonical sequence for", "the canonical sequence for beta", "canonical sequence for beta defensins", "sequence for beta defensins is", "for beta defensins is x2", "beta defensins is x2 10cx5", "defensins is x2 10cx5 6", "is x2 10cx5 6 g/a", "x2 10cx5 6 g/a xcx3", "10cx5 6 g/a xcx3 4cx9", "6 g/a xcx3 4cx9 13cx4", "g/a xcx3 4cx9 13cx4 7ccxn.", "xcx3 4cx9 13cx4 7ccxn. structurally", "4cx9 13cx4 7ccxn. structurally they", "13cx4 7ccxn. structurally they are", "7ccxn. structurally they are similar", "structurally they are similar to", "they are similar to alpha", "are similar to alpha defensins", "similar to alpha defensins but", "to alpha defensins but with", "alpha defensins but with much", "defensins but with much shorter", "but with much shorter pre", "with much shorter pre regions.", "much shorter pre regions. though", "shorter pre regions. though dimerization", "pre regions. though dimerization of", "regions. though dimerization of some", "though dimerization of some beta", "dimerization of some beta defensins", "of some beta defensins has", "some beta defensins has been", "beta defensins has been reported", "defensins has been reported this", "has been reported this is", "been reported this is not", "reported this is not the", "this is not the case", "is not the case for", "not the case for all", "the case for all and", "case for all and it", "for all and it is", "all and it is unclear", "and it is unclear whether", "it is unclear whether it", "is unclear whether it is", "unclear whether it is required", "whether it is required for", "it is required for function.", "is required for function. the", "required for function. the majority", "for function. the majority of", "function. the majority of functional", "the majority of functional studies", "majority of functional studies have", "of functional studies have focused", "functional studies have focused on", "studies have focused on beta", "have focused on beta defensin", "focused on beta defensin 103", "beta defensin 103 hbd3", "hbd3 which has", "which has the most significant", "has the most significant antimicrobial", "the most significant antimicrobial activity", "most significant antimicrobial activity at", "significant antimicrobial activity at physiological", "antimicrobial activity at physiological salt", "activity at physiological salt concentrations", "physiological salt concentrations harder", "salt concentrations harder et", "concentrations harder et al.", "harder et al. 2001 .", "et al. 2001 . beta", "al. 2001 . beta defensin", "2001 . beta defensin 103", "beta defensin 103 is", "defensin 103 is highly", "103 is highly cationic", "is highly cationic with a", "highly cationic with a net", "cationic with a net charge", "with a net charge of", "a net charge of +11", "net charge of +11 e0.", "of +11 e0. it", "+11 e0. it exhibits", "e0. it exhibits broad", "it exhibits broad spectrum antimicrobial", "exhibits broad spectrum antimicrobial activity", "broad spectrum antimicrobial activity against", "spectrum antimicrobial activity against gram", "antimicrobial activity against gram positive", "activity against gram positive bacteria", "against gram positive bacteria and", "gram positive bacteria and some", "positive bacteria and some gram", "bacteria and some gram negative", "and some gram negative bacteria", "gram negative bacteria harder", "negative bacteria harder et", "bacteria harder et al.", "al. 2001 though", "2001 though some", "though some species are highly", "some species are highly resistant", "are highly resistant sahly", "highly resistant sahly et", "resistant sahly et al.", "sahly et al. 2003 .", "et al. 2003 . sensitivity", "al. 2003 . sensitivity correlates", "2003 . sensitivity correlates with", ". sensitivity correlates with lipid", "sensitivity correlates with lipid composition", "correlates with lipid composition of", "with lipid composition of the", "lipid composition of the membrane", "of the membrane with", "the membrane with more", "membrane with more negatively", "with more negatively charged lipids", "more negatively charged lipids correlating", "negatively charged lipids correlating with", "charged lipids correlating with larger", "lipids correlating with larger beta", "correlating with larger beta defensin", "with larger beta defensin 103", "larger beta defensin 103 induced", "beta defensin 103 induced changes", "defensin 103 induced changes in", "103 induced changes in membrane", "induced changes in membrane capacitance", "in membrane capacitance bohling", "membrane capacitance bohling et", "capacitance bohling et al.", "bohling et al. 2006 .", "et al. 2006 . though", "al. 2006 . though membrane", "2006 . though membrane disruption", ". though membrane disruption is", "though membrane disruption is widely", "membrane disruption is widely believed", "disruption is widely believed to", "is widely believed to be", "widely believed to be the", "believed to be the primary", "to be the primary mechanism", "be the primary mechanism of", "primary mechanism of action of", "mechanism of action of beta", "of action of beta defensins", "action of beta defensins they", "of beta defensins they have", "beta defensins they have other", "defensins they have other antimicrobial", "they have other antimicrobial properties", "other antimicrobial properties such", "antimicrobial properties such as", "properties such as inhibition", "such as inhibition of cell", "as inhibition of cell wall", "inhibition of cell wall biosynthesis", "cell wall biosynthesis sass", "wall biosynthesis sass et", "biosynthesis sass et al.", "al. 2010 and", "2010 and chemoattractant", "and chemoattractant effects yang", "chemoattractant effects yang et", "effects yang et al.", "et al. 1999 niyonsaba", "al. 1999 niyonsaba et", "1999 niyonsaba et al.", "et al. 2002 2004", "al. 2002 2004 .", "2002 2004 . the", "2004 . the chemotactic activity", ". the chemotactic activity of", "the chemotactic activity of beta", "chemotactic activity of beta defensins", "activity of beta defensins 1", "hbd1 3 for memory", "3 for memory t", "for memory t cells and", "memory t cells and immature", "t cells and immature dcs", "cells and immature dcs is", "and immature dcs is mediated", "immature dcs is mediated through", "dcs is mediated through binding", "is mediated through binding to", "mediated through binding to the", "through binding to the chemokine", "binding to the chemokine receptor", "to the chemokine receptor ccr6", "the chemokine receptor ccr6 and", "chemokine receptor ccr6 and probably", "receptor ccr6 and probably another", "ccr6 and probably another unidentified", "and probably another unidentified gi", "probably another unidentified gi coupled", "another unidentified gi coupled receptor", "gi coupled receptor yang", "coupled receptor yang et", "receptor yang et al.", "et al. 1999 2000", "al. 1999 2000 .", "1999 2000 .
", "2000 .

like defensins", "

like defensins the", "
like defensins the human", "defensins the human cathelicidin", "the human cathelicidin ll37 peptide", "human cathelicidin ll37 peptide is", "cathelicidin ll37 peptide is rich", "ll37 peptide is rich in", "peptide is rich in positively", "is rich in positively charged", "in positively charged residues", "charged residues lehrer", "residues lehrer & ganz", "lehrer & ganz 2002 .
expression", "& ganz 2002 .
expression of", "ganz 2002 .
expression of certain", "2002 .
expression of certain beta", ".
expression of certain beta defensins", "of certain beta defensins can", "certain beta defensins can be", "beta defensins can be induced", "defensins can be induced in", "can be induced in response", "be induced in response to", "induced in response to various", "in response to various signals", "to various signals such", "various signals such as", "signals such as bacteria", "such as bacteria pathogen", "as bacteria pathogen associated", "bacteria pathogen associated molecular", "associated molecular patterns pamps", "pamps or proinflammatory", "or proinflammatory cytokines ganz", "proinflammatory cytokines ganz 2003", "ganz 2003 yang et", "2003 yang et al.", "yang et al. 2004 .", "et al. 2004 . like", "al. 2004 . like the", "2004 . like the alpha", ". like the alpha defensins", "the alpha defensins copy", "alpha defensins copy number", "defensins copy number variation", "copy number variation has been", "number variation has been reported", "variation has been reported for", "has been reported for defb4", "reported for defb4 defb103", "for defb4 defb103 and", "defb4 defb103 and defb104", "defb103 and defb104 with individuals", "and defb104 with individuals having", "defb104 with individuals having 2", "with individuals having 2 12", "individuals having 2 12 copies", "having 2 12 copies per", "2 12 copies per diploid", "12 copies per diploid genome.", "copies per diploid genome. in", "per diploid genome. in contrast", "diploid genome. in contrast defb1", "genome. in contrast defb1 does", "in contrast defb1 does not", "contrast defb1 does not show", "defb1 does not show such", "does not show such variation", "not show such variation but", "show such variation but exhibits", "such variation but exhibits a", "variation but exhibits a number", "but exhibits a number of", "exhibits a number of snps", "number of snps hollox", "of snps hollox et", "snps hollox et al.", "et al. 2003 linzmier", "al. 2003 linzmier &", "2003 linzmier & ganz", "linzmier & ganz 2005 ." ] }, { "record_id": "GLY_000594_1_58", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1461973", "r hsa", "hsa 1461973", "r hsa 1461973" ] }, { "record_id": "GLY_000594_1_58", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "the defensins", "defensins are", "are a", "a family", "family of", "of antimicrobial", "antimicrobial cationic", "cationic peptide", "peptide molecules", "molecules which", "which in", "in mammals", "mammals have", "have a", "a characteristic", "beta sheet", "sheet rich", "rich fold", "fold and", "and framework", "framework of", "of six", "six disulphide", "disulphide linked", "linked cysteines", "selsted &", "& ouellette", "ouellette 2005", "ganz 2003", "2003 .", ". human", "human defensin", "defensin peptides", "peptides have", "have two", "two subfamilies", "and beta", "beta defensins", "differing in", "in the", "the length", "length of", "of peptide", "peptide chain", "chain between", "between the", "the six", "six cysteines", "cysteines and", "and the", "the order", "order of", "of disulphide", "disulphide bond", "bond pairing", "pairing between", "between them.", "them. a", "a third", "third subfamily", "the theta", "theta defensins", "is derived", "derived from", "from alpha", "alpha defensins", "defensins prematurely", "prematurely truncated", "truncated by", "by a", "a stop", "stop codon", "codon between", "the third", "third and", "and fourth", "fourth cysteine", "cysteine residues.", "residues. the", "the translated", "translated products", "products are", "are shortened", "shortened to", "to nonapeptides", "covalently dimerized", "dimerized by", "by disulfide", "disulfide linkages", "and cyclized", "cyclized via", "via new", "new peptide", "peptide bonds", "bonds between", "the first", "first and", "and ninth", "ninth residues.", "residues. humans", "humans have", "have one", "one pseudogene", "pseudogene but", "but no", "no translated", "translated representatives", "representatives of", "of the", "theta class.
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the", "

the primary", "primary cellular", "cellular sources", "sources of", "of defensins", "are neutrophils", "epithelial cells", "cells and", "and intestinal", "intestinal paneth", "paneth cells.those", "cells.those expressed", "expressed in", "in neutrophils", "neutrophils and", "the gut", "gut are", "are predominantly", "predominantly constitutive", "while those", "those in", "in epithelial", "epithelial tissues", "tissues such", "such as", "as skin", "skin are", "are often", "often inducible", "inducible by", "by proinflammatory", "proinflammatory stimuli", "stimuli such", "as lps", "lps or", "or tnf", "tnf alpha.

defensins", "alpha.

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defensins", ".

defensins have", "have direct", "direct antimicrobial", "antimicrobial effects", "effects and", "and kill", "kill a", "a wide", "wide range", "range of", "of gram", "gram positive", "positive and", "and negative", "negative bacteria", "fungi and", "and some", "some viruses.", "viruses. the", "the primary", "primary antimicrobial", "antimicrobial action", "action of", "defensins is", "is permeabilization", "permeabilization of", "of microbial", "microbial target", "target membranes", "membranes but", "but several", "several additional", "additional mechanisms", "mechanisms have", "have been", "been suggested", "brogden 2005", "wilmes et", "al. 2011", "2011 .", ". defensins", "defensins and", "and related", "related antimicrobial", "antimicrobial peptides", "peptides such", "as cathelicidin", "cathelicidin bridge", "bridge the", "the innate", "innate and", "and acquired", "acquired immune", "immune responses.", "responses. in", "in addition", "addition to", "to their", "their antimicrobial", "antimicrobial properties", "cathelicidin and", "and several", "several defensins", "defensins show", "show receptor", "receptor mediated", "mediated chemotactic", "chemotactic activity", "activity for", "for immune", "immune cells", "cells such", "as monocytes", "t cells", "cells or", "or immature", "immature dcs", "induce cytokine", "cytokine production", "production by", "by monocytes", "monocytes and", "and epithelial", "modulate angiogenesis", "angiogenesis and", "and stimulate", "stimulate wound", "wound healing", "al. 1999", "rehaume &", "& hancock", "hancock 2008", "yeung et", "the defensins are", "defensins are a", "are a family", "a family of", "family of antimicrobial", "of antimicrobial cationic", "antimicrobial cationic peptide", "cationic peptide molecules", "peptide molecules which", "molecules which in", "which in mammals", "in mammals have", "mammals have a", "have a characteristic", "characteristic beta", "beta sheet rich", "sheet rich fold", "rich fold and", "fold and framework", "and framework of", "framework of six", "of six disulphide", "six disulphide linked", "disulphide linked cysteines", "cysteines selsted", "selsted & ouellette", "& ouellette 2005", "2005 ganz", "ganz 2003 .", "2003 . human", ". human defensin", "human defensin peptides", "defensin peptides have", "peptides have two", "have two subfamilies", "subfamilies alpha", "and beta defensins", "defensins differing", "differing in the", "in the length", "the length of", "length of peptide", "of peptide chain", "peptide chain between", "chain between the", "between the six", "the six cysteines", "six cysteines and", "cysteines and the", "and the order", "the order of", "order of disulphide", "of disulphide bond", "disulphide bond pairing", "bond pairing between", "pairing between them.", "between them. a", "them. a third", "a third subfamily", "subfamily the", "the theta defensins", "is derived from", "derived from alpha", "from alpha defensins", "alpha defensins prematurely", "defensins prematurely truncated", "prematurely truncated by", "truncated by a", "by a stop", "a stop codon", "stop codon between", "codon between the", "between the third", "the third and", "third and fourth", "and fourth cysteine", "fourth cysteine residues.", "cysteine residues. the", "residues. the translated", "the translated products", "translated products are", "products are shortened", "are shortened to", "shortened to nonapeptides", "nonapeptides covalently", "covalently dimerized by", "dimerized by disulfide", "by disulfide linkages", "linkages and", "and cyclized via", "cyclized via new", "via new peptide", "new peptide bonds", "peptide bonds between", "bonds between the", "between the first", "the first and", "first and ninth", "and ninth residues.", "ninth residues. humans", "residues. humans have", "humans have one", "have one pseudogene", "one pseudogene but", "pseudogene but no", "but no translated", "no translated representatives", "translated representatives of", "representatives of the", "of the theta", "the theta class.
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the", "structures.

the primary", "

the primary cellular", "primary cellular sources", "cellular sources of", "sources of defensins", "of defensins are", "defensins are neutrophils", "neutrophils epithelial", "epithelial cells and", "cells and intestinal", "and intestinal paneth", "intestinal paneth cells.those", "paneth cells.those expressed", "cells.those expressed in", "expressed in neutrophils", "in neutrophils and", "neutrophils and the", "and the gut", "the gut are", "gut are predominantly", "are predominantly constitutive", "constitutive while", "while those in", "those in epithelial", "in epithelial tissues", "epithelial tissues such", "tissues such as", "such as skin", "as skin are", "skin are often", "are often inducible", "often inducible by", "inducible by proinflammatory", "by proinflammatory stimuli", "proinflammatory stimuli such", "stimuli such as", "such as lps", "as lps or", "lps or tnf", "or tnf alpha.

defensins", "tnf alpha.

defensins are", "alpha.

defensins are translated", "are translated as", "translated as precursor", "as precursor polypeptides", "precursor polypeptides that", "polypeptides that include", "that include a", "include a typical", "a typical signal", "typical signal peptide", "signal peptide or", "peptide or prepiece", "or prepiece that", "prepiece that is", "that is cleaved", "is cleaved in", "cleaved in the", "in the golgi", "the golgi body", "body and", "and a propiece", "propiece cleaved", "cleaved by differing", "by differing mechanisms", "differing mechanisms to", "mechanisms to produce", "to produce the", "produce the mature", "the mature defensin.", "mature defensin. mature", "defensin. mature defensin", "mature defensin peptides", "defensin peptides can", "peptides can be", "can be further", "be further processed", "further processed by", "processed by removal", "by removal of", "removal of individual", "of individual n", "individual n terminal", "n terminal residues", "residues yang", "yang et al.", "et al. 2004", "al. 2004 .", "2004 . this", ". this may", "this may be", "may be a", "be a mechanism", "a mechanism to", "mechanism to broaden", "to broaden the", "broaden the activity", "the activity profile", "activity profile of", "profile of defensins", "defensins ghosh", "ghosh et al.", "et al. 2002", "al. 2002 .

defensins", "2002 .

defensins have", ".

defensins have direct", "have direct antimicrobial", "direct antimicrobial effects", "antimicrobial effects and", "effects and kill", "and kill a", "kill a wide", "a wide range", "wide range of", "range of gram", "of gram positive", "gram positive and", "positive and negative", "and negative bacteria", "bacteria fungi", "fungi and some", "and some viruses.", "some viruses. the", "viruses. the primary", "the primary antimicrobial", "primary antimicrobial action", "antimicrobial action of", "action of defensins", "of defensins is", "defensins is permeabilization", "is permeabilization of", "permeabilization of microbial", "of microbial target", "microbial target membranes", "target membranes but", "membranes but several", "but several additional", "several additional mechanisms", "additional mechanisms have", "mechanisms have been", "have been suggested", "suggested brogden", "2005 wilmes", "wilmes et al.", "et al. 2011", "al. 2011 .", "2011 . defensins", ". defensins and", "defensins and related", "and related antimicrobial", "related antimicrobial peptides", "antimicrobial peptides such", "peptides such as", "such as cathelicidin", "as cathelicidin bridge", "cathelicidin bridge the", "bridge the innate", "the innate and", "innate and acquired", "and acquired immune", "acquired immune responses.", "immune responses. in", "responses. in addition", "in addition to", "addition to their", "to their antimicrobial", "their antimicrobial properties", "properties cathelicidin", "cathelicidin and several", "and several defensins", "several defensins show", "defensins show receptor", "show receptor mediated", "receptor mediated chemotactic", "mediated chemotactic activity", "chemotactic activity for", "activity for immune", "for immune cells", "immune cells such", "cells such as", "such as monocytes", "monocytes t", "t cells or", "cells or immature", "or immature dcs", "dcs induce", "induce cytokine production", "cytokine production by", "production by monocytes", "by monocytes and", "monocytes and epithelial", "and epithelial cells", "cells modulate", "modulate angiogenesis and", "angiogenesis and stimulate", "and stimulate wound", "stimulate wound healing", "healing yang", "et al. 1999", "1999 2000", "2000 2004", "2004 rehaume", "rehaume & hancock", "& hancock 2008", "2008 yeung", "yeung et al.", "the defensins are a", "defensins are a family", "are a family of", "a family of antimicrobial", "family of antimicrobial cationic", "of antimicrobial cationic peptide", "antimicrobial cationic peptide molecules", "cationic peptide molecules which", "peptide molecules which in", "molecules which in mammals", "which in mammals have", "in mammals have a", "mammals have a characteristic", "a characteristic beta", "characteristic beta sheet", "beta sheet rich fold", "sheet rich fold and", "rich fold and framework", "fold and framework of", "and framework of six", "framework of six disulphide", "of six disulphide linked", "six disulphide linked cysteines", "linked cysteines selsted", "cysteines selsted &", "selsted & ouellette 2005", "ouellette 2005 ganz", "2005 ganz 2003", "ganz 2003 . human", "2003 . human defensin", ". human defensin peptides", "human defensin peptides have", "defensin peptides have two", "peptides have two subfamilies", "two subfamilies alpha", "beta defensins differing", "defensins differing in", "differing in the length", "in the length of", "the length of peptide", "length of peptide chain", "of peptide chain between", "peptide chain between the", "chain between the six", "between the six cysteines", "the six cysteines and", "six cysteines and the", "cysteines and the order", "and the order of", "the order of disulphide", "order of disulphide bond", "of disulphide bond pairing", "disulphide bond pairing between", "bond pairing between them.", "pairing between them. a", "between them. a third", "them. a third subfamily", "third subfamily the", "subfamily the theta", "theta defensins is", "defensins is derived", "is derived from alpha", "derived from alpha defensins", "from alpha defensins prematurely", "alpha defensins prematurely truncated", "defensins prematurely truncated by", "prematurely truncated by a", "truncated by a stop", "by a stop codon", "a stop codon between", "stop codon between the", "codon between the third", "between the third and", "the third and fourth", "third and fourth cysteine", "and fourth cysteine residues.", "fourth cysteine residues. the", "cysteine residues. the translated", "residues. the translated products", "the translated products are", "translated products are shortened", "products are shortened to", "are shortened to nonapeptides", "to nonapeptides covalently", "nonapeptides covalently dimerized", "covalently dimerized by disulfide", "dimerized by disulfide linkages", "disulfide linkages and", "linkages and cyclized", "and cyclized via new", "cyclized via new peptide", "via new peptide bonds", "new peptide bonds between", "peptide bonds between the", "bonds between the first", "between the first and", "the first and ninth", "first and ninth residues.", "and ninth residues. humans", "ninth residues. humans have", "residues. humans have one", "humans have one pseudogene", "have one pseudogene but", "one pseudogene but no", "pseudogene but no translated", "but no translated representatives", "no translated representatives of", "translated representatives of the", "representatives of the theta", "of the theta class.
in", "the theta class.
in solution", "theta class.
in solution most", "class.
in solution most alpha", "solution most alpha and", "most alpha and beta", "alpha and beta defensins", "and beta defensins are", "beta defensins are monomers", "defensins are monomers but", "are monomers but can", "monomers but can form", "but can form dimers", "can form dimers and", "form dimers and higher", "dimers and higher order", "and higher order structures.", "higher order structures.

the", "order structures.

the primary", "structures.

the primary cellular", "

the primary cellular sources", "primary cellular sources of", "cellular sources of defensins", "sources of defensins are", "of defensins are neutrophils", "are neutrophils epithelial", "neutrophils epithelial cells", "epithelial cells and intestinal", "cells and intestinal paneth", "and intestinal paneth cells.those", "intestinal paneth cells.those expressed", "paneth cells.those expressed in", "cells.those expressed in neutrophils", "expressed in neutrophils and", "in neutrophils and the", "neutrophils and the gut", "and the gut are", "the gut are predominantly", "gut are predominantly constitutive", "predominantly constitutive while", "constitutive while those", "while those in epithelial", "those in epithelial tissues", "in epithelial tissues such", "epithelial tissues such as", "tissues such as skin", "such as skin are", "as skin are often", "skin are often inducible", "are often inducible by", "often inducible by proinflammatory", "inducible by proinflammatory stimuli", "by proinflammatory stimuli such", "proinflammatory stimuli such as", "stimuli such as lps", "such as lps or", "as lps or tnf", "lps or tnf alpha.

defensins", "or tnf alpha.

defensins are", "tnf alpha.

defensins are translated", "alpha.

defensins are translated as", "are translated as precursor", "translated as precursor polypeptides", "as precursor polypeptides that", "precursor polypeptides that include", "polypeptides that include a", "that include a typical", "include a typical signal", "a typical signal peptide", "typical signal peptide or", "signal peptide or prepiece", "peptide or prepiece that", "or prepiece that is", "prepiece that is cleaved", "that is cleaved in", "is cleaved in the", "cleaved in the golgi", "in the golgi body", "golgi body and", "body and a", "a propiece cleaved", "propiece cleaved by", "cleaved by differing mechanisms", "by differing mechanisms to", "differing mechanisms to produce", "mechanisms to produce the", "to produce the mature", "produce the mature defensin.", "the mature defensin. mature", "mature defensin. mature defensin", "defensin. mature defensin peptides", "mature defensin peptides can", "defensin peptides can be", "peptides can be further", "can be further processed", "be further processed by", "further processed by removal", "processed by removal of", "by removal of individual", "removal of individual n", "of individual n terminal", "individual n terminal residues", "terminal residues yang", "residues yang et", "yang et al. 2004", "et al. 2004 .", "al. 2004 . this", "2004 . this may", ". this may be", "this may be a", "may be a mechanism", "be a mechanism to", "a mechanism to broaden", "mechanism to broaden the", "to broaden the activity", "broaden the activity profile", "the activity profile of", "activity profile of defensins", "of defensins ghosh", "defensins ghosh et", "ghosh et al. 2002", "et al. 2002 .

defensins", "al. 2002 .

defensins have", "2002 .

defensins have direct", ".

defensins have direct antimicrobial", "have direct antimicrobial effects", "direct antimicrobial effects and", "antimicrobial effects and kill", "effects and kill a", "and kill a wide", "kill a wide range", "a wide range of", "wide range of gram", "range of gram positive", "of gram positive and", "gram positive and negative", "positive and negative bacteria", "negative bacteria fungi", "bacteria fungi and", "fungi and some viruses.", "and some viruses. the", "some viruses. the primary", "viruses. the primary antimicrobial", "the primary antimicrobial action", "primary antimicrobial action of", "antimicrobial action of defensins", "action of defensins is", "of defensins is permeabilization", "defensins is permeabilization of", "is permeabilization of microbial", "permeabilization of microbial target", "of microbial target membranes", "microbial target membranes but", "target membranes but several", "membranes but several additional", "but several additional mechanisms", "several additional mechanisms have", "additional mechanisms have been", "mechanisms have been suggested", "been suggested brogden", "suggested brogden 2005", "brogden 2005 wilmes", "2005 wilmes et", "wilmes et al. 2011", "et al. 2011 .", "al. 2011 . defensins", "2011 . defensins and", ". defensins and related", "defensins and related antimicrobial", "and related antimicrobial peptides", "related antimicrobial peptides such", "antimicrobial peptides such as", "peptides such as cathelicidin", "such as cathelicidin bridge", "as cathelicidin bridge the", "cathelicidin bridge the innate", "bridge the innate and", "the innate and acquired", "innate and acquired immune", "and acquired immune responses.", "acquired immune responses. in", "immune responses. in addition", "responses. in addition to", "in addition to their", "addition to their antimicrobial", "to their antimicrobial properties", "antimicrobial properties cathelicidin", "properties cathelicidin and", "cathelicidin and several defensins", "and several defensins show", "several defensins show receptor", "defensins show receptor mediated", "show receptor mediated chemotactic", "receptor mediated chemotactic activity", "mediated chemotactic activity for", "chemotactic activity for immune", "activity for immune cells", "for immune cells such", "immune cells such as", "cells such as monocytes", "as monocytes t", "monocytes t cells", "t cells or immature", "cells or immature dcs", "immature dcs induce", "dcs induce cytokine", "induce cytokine production by", "cytokine production by monocytes", "production by monocytes and", "by monocytes and epithelial", "monocytes and epithelial cells", "epithelial cells modulate", "cells modulate angiogenesis", "modulate angiogenesis and stimulate", "angiogenesis and stimulate wound", "and stimulate wound healing", "wound healing yang", "healing yang et", "yang et al. 1999", "al. 1999 2000", "2004 rehaume &", "rehaume & hancock 2008", "hancock 2008 yeung", "2008 yeung et", "yeung et al. 2011", "the defensins are a family", "defensins are a family of", "are a family of antimicrobial", "a family of antimicrobial cationic", "family of antimicrobial cationic peptide", "of antimicrobial cationic peptide molecules", "antimicrobial cationic peptide molecules which", "cationic peptide molecules which in", "peptide molecules which in mammals", "molecules which in mammals have", "which in mammals have a", "in mammals have a characteristic", "have a characteristic beta", "a characteristic beta sheet", "characteristic beta sheet rich", "beta sheet rich fold and", "sheet rich fold and framework", "rich fold and framework of", "fold and framework of six", "and framework of six disulphide", "framework of six disulphide linked", "of six disulphide linked cysteines", "disulphide linked cysteines selsted", "linked cysteines selsted &", "cysteines selsted & ouellette", "& ouellette 2005 ganz", "ouellette 2005 ganz 2003", "2005 ganz 2003 .", "ganz 2003 . human defensin", "2003 . human defensin peptides", ". human defensin peptides have", "human defensin peptides have two", "defensin peptides have two subfamilies", "have two subfamilies alpha", "subfamilies alpha and", "and beta defensins differing", "beta defensins differing in", "defensins differing in the", "differing in the length of", "in the length of peptide", "the length of peptide chain", "length of peptide chain between", "of peptide chain between the", "peptide chain between the six", "chain between the six cysteines", "between the six cysteines and", "the six cysteines and the", "six cysteines and the order", "cysteines and the order of", "and the order of disulphide", "the order of disulphide bond", "order of disulphide bond pairing", "of disulphide bond pairing between", "disulphide bond pairing between them.", "bond pairing between them. a", "pairing between them. a third", "between them. a third subfamily", "a third subfamily the", "third subfamily the theta", "subfamily the theta defensins", "the theta defensins is", "theta defensins is derived", "defensins is derived from", "is derived from alpha defensins", "derived from alpha defensins prematurely", "from alpha defensins prematurely truncated", "alpha defensins prematurely truncated by", "defensins prematurely truncated by a", "prematurely truncated by a stop", "truncated by a stop codon", "by a stop codon between", "a stop codon between the", "stop codon between the third", "codon between the third and", "between the third and fourth", "the third and fourth cysteine", "third and fourth cysteine residues.", "and fourth cysteine residues. the", "fourth cysteine residues. the translated", "cysteine residues. the translated products", "residues. the translated products are", "the translated products are shortened", "translated products are shortened to", "products are shortened to nonapeptides", "shortened to nonapeptides covalently", "to nonapeptides covalently dimerized", "nonapeptides covalently dimerized by", "covalently dimerized by disulfide linkages", "by disulfide linkages and", "disulfide linkages and cyclized", "linkages and cyclized via", "and cyclized via new peptide", "cyclized via new peptide bonds", "via new peptide bonds between", "new peptide bonds between the", "peptide bonds between the first", "bonds between the first and", "between the first and ninth", "the first and ninth residues.", "first and ninth residues. humans", "and ninth residues. humans have", "ninth residues. humans have one", "residues. humans have one pseudogene", "humans have one pseudogene but", "have one pseudogene but no", "one pseudogene but no translated", "pseudogene but no translated representatives", "but no translated representatives of", "no translated representatives of the", "translated representatives of the theta", "representatives of the theta class.
in", "of the theta class.
in solution", "the theta class.
in solution most", "theta class.
in solution most alpha", "class.
in solution most alpha and", "solution most alpha and beta", "most alpha and beta defensins", "alpha and beta defensins are", "and beta defensins are monomers", "beta defensins are monomers but", "defensins are monomers but can", "are monomers but can form", "monomers but can form dimers", "but can form dimers and", "can form dimers and higher", "form dimers and higher order", "dimers and higher order structures.", "and higher order structures.

the", "higher order structures.

the primary", "order structures.

the primary cellular", "structures.

the primary cellular sources", "

the primary cellular sources of", "primary cellular sources of defensins", "cellular sources of defensins are", "sources of defensins are neutrophils", "defensins are neutrophils epithelial", "are neutrophils epithelial cells", "neutrophils epithelial cells and", "epithelial cells and intestinal paneth", "cells and intestinal paneth cells.those", "and intestinal paneth cells.those expressed", "intestinal paneth cells.those expressed in", "paneth cells.those expressed in neutrophils", "cells.those expressed in neutrophils and", "expressed in neutrophils and the", "in neutrophils and the gut", "neutrophils and the gut are", "and the gut are predominantly", "the gut are predominantly constitutive", "are predominantly constitutive while", "predominantly constitutive while those", "constitutive while those in", "while those in epithelial tissues", "those in epithelial tissues such", "in epithelial tissues such as", "epithelial tissues such as skin", "tissues such as skin are", "such as skin are often", "as skin are often inducible", "skin are often inducible by", "are often inducible by proinflammatory", "often inducible by proinflammatory stimuli", "inducible by proinflammatory stimuli such", "by proinflammatory stimuli such as", "proinflammatory stimuli such as lps", "stimuli such as lps or", "such as lps or tnf", "as lps or tnf alpha.

defensins", "lps or tnf alpha.

defensins are", "or tnf alpha.

defensins are translated", "tnf alpha.

defensins are translated as", "alpha.

defensins are translated as precursor", "are translated as precursor polypeptides", "translated as precursor polypeptides that", "as precursor polypeptides that include", "precursor polypeptides that include a", "polypeptides that include a typical", "that include a typical signal", "include a typical signal peptide", "a typical signal peptide or", "typical signal peptide or prepiece", "signal peptide or prepiece that", "peptide or prepiece that is", "or prepiece that is cleaved", "prepiece that is cleaved in", "that is cleaved in the", "is cleaved in the golgi", "cleaved in the golgi body", "the golgi body and", "golgi body and a", "body and a propiece", "and a propiece cleaved", "a propiece cleaved by", "propiece cleaved by differing", "cleaved by differing mechanisms to", "by differing mechanisms to produce", "differing mechanisms to produce the", "mechanisms to produce the mature", "to produce the mature defensin.", "produce the mature defensin. mature", "the mature defensin. mature defensin", "mature defensin. mature defensin peptides", "defensin. mature defensin peptides can", "mature defensin peptides can be", "defensin peptides can be further", "peptides can be further processed", "can be further processed by", "be further processed by removal", "further processed by removal of", "processed by removal of individual", "by removal of individual n", "removal of individual n terminal", "of individual n terminal residues", "n terminal residues yang", "terminal residues yang et", "residues yang et al.", "yang et al. 2004 .", "et al. 2004 . this", "al. 2004 . this may", "2004 . this may be", ". this may be a", "this may be a mechanism", "may be a mechanism to", "be a mechanism to broaden", "a mechanism to broaden the", "mechanism to broaden the activity", "to broaden the activity profile", "broaden the activity profile of", "the activity profile of defensins", "profile of defensins ghosh", "of defensins ghosh et", "defensins ghosh et al.", "ghosh et al. 2002 .

defensins", "et al. 2002 .

defensins have", "al. 2002 .

defensins have direct", "2002 .

defensins have direct antimicrobial", ".

defensins have direct antimicrobial effects", "have direct antimicrobial effects and", "direct antimicrobial effects and kill", "antimicrobial effects and kill a", "effects and kill a wide", "and kill a wide range", "kill a wide range of", "a wide range of gram", "wide range of gram positive", "range of gram positive and", "of gram positive and negative", "gram positive and negative bacteria", "and negative bacteria fungi", "negative bacteria fungi and", "bacteria fungi and some", "fungi and some viruses. the", "and some viruses. the primary", "some viruses. the primary antimicrobial", "viruses. the primary antimicrobial action", "the primary antimicrobial action of", "primary antimicrobial action of defensins", "antimicrobial action of defensins is", "action of defensins is permeabilization", "of defensins is permeabilization of", "defensins is permeabilization of microbial", "is permeabilization of microbial target", "permeabilization of microbial target membranes", "of microbial target membranes but", "microbial target membranes but several", "target membranes but several additional", "membranes but several additional mechanisms", "but several additional mechanisms have", "several additional mechanisms have been", "additional mechanisms have been suggested", "have been suggested brogden", "been suggested brogden 2005", "brogden 2005 wilmes et", "2005 wilmes et al.", "wilmes et al. 2011 .", "et al. 2011 . defensins", "al. 2011 . defensins and", "2011 . defensins and related", ". defensins and related antimicrobial", "defensins and related antimicrobial peptides", "and related antimicrobial peptides such", "related antimicrobial peptides such as", "antimicrobial peptides such as cathelicidin", "peptides such as cathelicidin bridge", "such as cathelicidin bridge the", "as cathelicidin bridge the innate", "cathelicidin bridge the innate and", "bridge the innate and acquired", "the innate and acquired immune", "innate and acquired immune responses.", "and acquired immune responses. in", "acquired immune responses. in addition", "immune responses. in addition to", "responses. in addition to their", "in addition to their antimicrobial", "addition to their antimicrobial properties", "their antimicrobial properties cathelicidin", "antimicrobial properties cathelicidin and", "properties cathelicidin and several", "cathelicidin and several defensins show", "and several defensins show receptor", "several defensins show receptor mediated", "defensins show receptor mediated chemotactic", "show receptor mediated chemotactic activity", "receptor mediated chemotactic activity for", "mediated chemotactic activity for immune", "chemotactic activity for immune cells", "activity for immune cells such", "for immune cells such as", "immune cells such as monocytes", "such as monocytes t", "as monocytes t cells", "monocytes t cells or", "t cells or immature dcs", "or immature dcs induce", "immature dcs induce cytokine", "dcs induce cytokine production", "induce cytokine production by monocytes", "cytokine production by monocytes and", "production by monocytes and epithelial", "by monocytes and epithelial cells", "and epithelial cells modulate", "epithelial cells modulate angiogenesis", "cells modulate angiogenesis and", "modulate angiogenesis and stimulate wound", "angiogenesis and stimulate wound healing", "stimulate wound healing yang", "wound healing yang et", "healing yang et al.", "et al. 1999 2000", "1999 2000 2004", "2000 2004 rehaume", "2004 rehaume & hancock", "& hancock 2008 yeung", "hancock 2008 yeung et", "2008 yeung et al.", "yeung et al. 2011 ." ] }, { "record_id": "GLY_000594_1_59", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1474228", "r hsa", "hsa 1474228", "r hsa 1474228" ] }, { "record_id": "GLY_000594_1_59", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "degradation of", "of the", "the extracellular", "extracellular matrix", "degradation of the", "of the extracellular", "the extracellular matrix", "degradation of the extracellular", "of the extracellular matrix", "degradation of the extracellular matrix", "matrix metalloproteinases", "previously referred", "referred to", "to as", "as matrixins", "matrixins because", "because of", "of their", "their role", "role in", "in degradation", "are zinc", "zinc and", "and calcium", "calcium dependent", "dependent proteases", "proteases belonging", "belonging to", "to the", "the metzincin", "metzincin family.", "family. they", "they contain", "contain a", "a characteristic", "characteristic zinc", "zinc binding", "binding motif", "motif hexxhxxgxxh", "stocker &", "& bode", "bode 1995", "and a", "a conserved", "conserved methionine", "methionine which", "which forms", "forms a", "a met", "met turn.", "turn. humans", "humans have", "have 24", "24 mmp", "mmp genes", "genes giving", "giving rise", "rise to", "to 23", "23 mmp", "mmp proteins", "as mmp23", "mmp23 is", "is 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"timps .", "are best", "best known", "known for", "for their", "the degradation", "degradation and", "and removal", "removal of", "of ecm", "ecm molecules.", "molecules. in", "in addition", "cleavage of", "the ecm", "ecm and", "and other", "other cell", "cell surface", "surface molecules", "molecules can", "can release", "release ecm", "ecm bound", "bound growth", "growth factors", "a number", "number of", "of non", "non ecm", "ecm proteins", "proteins are", "are substrates", "substrates of", "of mmps", "nagase et", "al. 2006", "2006 .", "mmps can", "be divided", "divided into", "into subgroups", "subgroups based", "based on", "on domain", "domain structure", "structure and", "and substrate", "specificity but", "but it", "it is", "is clear", "clear that", "that these", "these are", "are somewhat", "somewhat artificial", "many mmps", "mmps belong", "belong to", "to more", "more than", "than one", "one functional", "functional group", "vise &", "& nagase", "nagase 2003", "somerville et", "al. 2003", "2003 .", "metalloproteinases mmps", "previously referred to", "referred to as", "to as matrixins", "as matrixins because", "matrixins because of", "because of their", "of their role", "their role in", "role in degradation", "in degradation of", "matrix ecm", "are zinc and", "zinc and calcium", "and calcium dependent", "calcium dependent proteases", "dependent proteases belonging", "proteases belonging to", "belonging to the", "to the metzincin", "the metzincin family.", "metzincin family. they", "family. they contain", "they contain a", "contain a characteristic", "a characteristic zinc", "characteristic zinc binding", "zinc binding motif", "binding motif hexxhxxgxxh", "hexxhxxgxxh stocker", "stocker & bode", "& bode 1995", "1995 and", "and a conserved", "a conserved methionine", "conserved methionine which", "methionine which forms", "which forms a", "forms a met", "a met turn.", "met turn. humans", "turn. humans have", "humans have 24", "have 24 mmp", "24 mmp genes", "mmp genes giving", "genes giving rise", "giving rise to", "rise to 23", "to 23 mmp", "23 mmp proteins", "proteins as", "as mmp23 is", "mmp23 is encoded", "is encoded by", "encoded by two", "by two identical", "two identical genes.", "identical genes. all", "genes. all mmps", "all mmps contain", "mmps contain an", "contain an n", "an n terminal", "n terminal secretory", "terminal secretory signal", "secretory signal peptide", "signal peptide and", "peptide and a", "and a prodomain", "a prodomain with", "prodomain with a", "with a conserved", "a conserved prcgxpd", "conserved prcgxpd motif", "prcgxpd motif that", "motif that in", "that in the", "in the inactive", "the inactive enzyme", "inactive enzyme is", "enzyme is localized", "is localized with", "localized with the", "with the catalytic", "the catalytic site", "site the", "the cysteine acting", "cysteine acting as", "acting as a", "as a fourth", "a fourth unpaired", "fourth unpaired ligand", "unpaired ligand for", "ligand for the", "for the catalytic", "the catalytic zinc", "catalytic zinc atom.", "zinc atom. activation", "atom. activation involves", "activation involves delocalization", "involves delocalization of", "delocalization of the", "of the domain", "the domain containing", "domain containing this", "containing this cysteine", "this cysteine by", "cysteine by a", "by a conformational", "a conformational change", "conformational change or", "change or proteolytic", "or proteolytic cleavage", "cleavage a", "a mechanism referred", "mechanism referred to", "to as the", "as the cysteine", "the cysteine switch", "switch van", "van wart &", "wart & birkedal", "& birkedal hansen", "birkedal hansen 1990", "hansen 1990 .", ". most", "most mmps are", "mmps are secreted", "are secreted but", "secreted but the", "but the membrane", "the membrane type", "membrane type mt", "type mt mmps", "mt mmps are", "mmps are membrane", "are membrane anchored", "membrane anchored and", "anchored and some", "and some mmps", "some mmps may", "mmps may act", "may act on", "act on intracellular", "on intracellular proteins.", "intracellular proteins. various", "proteins. various domains", "various domains determine", "domains determine substrate", "determine substrate specificity", "specificity cell", "cell localization and", "localization and activation", "activation hadler", "hadler olsen et", "olsen et al.", "et al. 2011", "al. 2011 .", "2011 . mmps", ". mmps are", "mmps are regulated", "are regulated by", "regulated by transcription", "transcription cellular", "location most", "most are not", "are not activated", "not activated until", "activated until secreted", "activating proteinases that", "proteinases that can", "that can be", "can be other", "be other mmps", "mmps and", "and by metalloproteinase", "by metalloproteinase inhibitors", "metalloproteinase inhibitors such", "inhibitors such as", "such as the", "as the tissue", "the tissue inhibitors", "tissue inhibitors of", "inhibitors of metalloproteinases", "metalloproteinases timps", "timps . mmps", "mmps are best", "are best known", "best known for", "known for their", "for their role", "role in the", "in the degradation", "the degradation and", "degradation and removal", "and removal of", "removal of ecm", "of ecm molecules.", "ecm molecules. in", "molecules. in addition", "addition cleavage", "cleavage of the", "of the ecm", "the ecm and", "ecm and other", "and other cell", "other cell surface", "cell surface molecules", "surface molecules can", "molecules can release", "can release ecm", "release ecm bound", "ecm bound growth", "bound growth factors", "factors and", "and a number", "a number of", "number of non", "of non ecm", "non ecm proteins", "ecm proteins are", "proteins are substrates", "are substrates of", "substrates of mmps", "mmps nagase", "nagase et al.", "et al. 2006", "al. 2006 .", "2006 . mmps", ". mmps can", "mmps can be", "can be divided", "be divided into", "divided into subgroups", "into subgroups based", "subgroups based on", "based on domain", "on domain structure", "domain structure and", "structure and substrate", "and substrate specificity", "substrate specificity but", "specificity but it", "but it is", "it is clear", "is clear that", "clear that these", "that these are", "these are somewhat", "are somewhat artificial", "artificial many", "many mmps belong", "mmps belong to", "belong to more", "to more than", "more than one", "than one functional", "one functional group", "group vise", "vise & nagase", "& nagase 2003", "2003 somerville", "somerville et al.", "et al. 2003", "al. 2003 .", "matrix metalloproteinases mmps", "mmps previously", "previously referred to as", "referred to as matrixins", "to as matrixins because", "as matrixins because of", "matrixins because of their", "because of their role", "of their role in", "their role in degradation", "role in degradation of", "in degradation of the", "extracellular matrix ecm", "ecm are", "are zinc and calcium", "zinc and calcium dependent", "and calcium dependent proteases", "calcium dependent proteases belonging", "dependent proteases belonging to", "proteases belonging to the", "belonging to the metzincin", "to the metzincin family.", "the metzincin family. they", "metzincin family. they contain", "family. they contain a", "they contain a characteristic", "contain a characteristic zinc", "a characteristic zinc binding", "characteristic zinc binding motif", "zinc binding motif hexxhxxgxxh", "motif hexxhxxgxxh stocker", "hexxhxxgxxh stocker &", "stocker & bode 1995", "bode 1995 and", "1995 and a", "and a conserved methionine", "a conserved methionine which", "conserved methionine which forms", "methionine which forms a", "which forms a met", "forms a met turn.", "a met turn. humans", "met turn. humans have", "turn. humans have 24", "humans have 24 mmp", "have 24 mmp genes", "24 mmp genes giving", "mmp genes giving rise", "genes giving rise to", "giving rise to 23", "rise to 23 mmp", "to 23 mmp proteins", "mmp proteins as", "proteins as mmp23", "as mmp23 is encoded", "mmp23 is encoded by", "is encoded by two", "encoded by two identical", "by two identical genes.", "two identical genes. all", "identical genes. all mmps", "genes. all mmps contain", "all mmps contain an", "mmps contain an n", "contain an n terminal", "an n terminal secretory", "n terminal secretory signal", "terminal secretory signal peptide", "secretory signal peptide and", "signal peptide and a", "peptide and a prodomain", "and a prodomain with", "a prodomain with a", "prodomain with a conserved", "with a conserved prcgxpd", "a conserved prcgxpd motif", "conserved prcgxpd motif that", "prcgxpd motif that in", "motif that in the", "that in the inactive", "in the inactive enzyme", "the inactive enzyme is", "inactive enzyme is localized", "enzyme is localized with", "is localized with the", "localized with the catalytic", "with the catalytic site", "catalytic site the", "site the cysteine", "the cysteine acting as", "cysteine acting as a", "acting as a fourth", "as a fourth unpaired", "a fourth unpaired ligand", "fourth unpaired ligand for", "unpaired ligand for the", "ligand for the catalytic", "for the catalytic zinc", "the catalytic zinc atom.", "catalytic zinc atom. activation", "zinc atom. activation involves", "atom. activation involves delocalization", "activation involves delocalization of", "involves delocalization of the", "delocalization of the domain", "of the domain containing", "the domain containing this", "domain containing this cysteine", "containing this cysteine by", "this cysteine by a", "cysteine by a conformational", "by a conformational change", "a conformational change or", "conformational change or proteolytic", "change or proteolytic cleavage", "proteolytic cleavage a", "cleavage a mechanism", "a mechanism referred to", "mechanism referred to as", "referred to as the", "to as the cysteine", "as the cysteine switch", "cysteine switch van", "switch van wart", "van wart & birkedal", "wart & birkedal hansen", "& birkedal hansen 1990", "birkedal hansen 1990 .", "1990 . most", ". most mmps", "most mmps are secreted", "mmps are secreted but", "are secreted but the", "secreted but the membrane", "but the membrane type", "the membrane type mt", "membrane type mt mmps", "type mt mmps are", "mt mmps are membrane", "mmps are membrane anchored", "are membrane anchored and", "membrane anchored and some", "anchored and some mmps", "and some mmps may", "some mmps may act", "mmps may act on", "may act on intracellular", "act on intracellular proteins.", "on intracellular proteins. various", "intracellular proteins. various domains", "proteins. various domains determine", "various domains determine substrate", "domains determine substrate specificity", "substrate specificity cell", "specificity cell localization", "cell localization and activation", "and activation hadler", "activation hadler olsen", "hadler olsen et al.", "olsen et al. 2011", "et al. 2011 .", "al. 2011 . mmps", "2011 . mmps are", ". mmps are regulated", "mmps are regulated by", "are regulated by transcription", "by transcription cellular", "transcription cellular location", "cellular location most", "location most are", "most are not activated", "are not activated until", "not activated until secreted", "secreted activating", "activating proteinases that can", "proteinases that can be", "that can be other", "can be other mmps", "other mmps and", "mmps and by", "and by metalloproteinase inhibitors", "by metalloproteinase inhibitors such", "metalloproteinase inhibitors such as", "inhibitors such as the", "such as the tissue", "as the tissue inhibitors", "the tissue inhibitors of", "tissue inhibitors of metalloproteinases", "of metalloproteinases timps", "metalloproteinases timps .", "timps . mmps are", ". mmps are best", "mmps are best known", "are best known for", "best known for their", "known for their role", "for their role in", "their role in the", "role in the degradation", "in the degradation and", "the degradation and removal", "degradation and removal of", "and removal of ecm", "removal of ecm molecules.", "of ecm molecules. in", "ecm molecules. in addition", "in addition cleavage", "addition cleavage of", "cleavage of the ecm", "of the ecm and", "the ecm and other", "ecm and other cell", "and other cell surface", "other cell surface molecules", "cell surface molecules can", "surface molecules can release", "molecules can release ecm", "can release ecm bound", "release ecm bound growth", "ecm bound growth factors", "growth factors and", "factors and a", "and a number of", "a number of non", "number of non ecm", "of non ecm proteins", "non ecm proteins are", "ecm proteins are substrates", "proteins are substrates of", "are substrates of mmps", "of mmps nagase", "mmps nagase et", "nagase et al. 2006", "et al. 2006 .", "al. 2006 . mmps", "2006 . mmps can", ". mmps can be", "mmps can be divided", "can be divided into", "be divided into subgroups", "divided into subgroups based", "into subgroups based on", "subgroups based on domain", "based on domain structure", "on domain structure and", "domain structure and substrate", "structure and substrate specificity", "and substrate specificity but", "substrate specificity but it", "specificity but it is", "but it is clear", "it is clear that", "is clear that these", "clear that these are", "that these are somewhat", "these are somewhat artificial", "somewhat artificial many", "artificial many mmps", "many mmps belong to", "mmps belong to more", "belong to more than", "to more than one", "more than one functional", "than one functional group", "functional group vise", "group vise &", "vise & nagase 2003", "nagase 2003 somerville", "2003 somerville et", "somerville et al. 2003", "et al. 2003 .", "mmps previously referred", "previously referred to as matrixins", "referred to as matrixins because", "to as matrixins because of", "as matrixins because of their", "matrixins because of their role", "because of their role in", "of their role in degradation", "their role in degradation of", "role in degradation of the", "in degradation of the extracellular", "the extracellular matrix ecm", "ecm are zinc", "are zinc and calcium dependent", "zinc and calcium dependent proteases", "and calcium dependent proteases belonging", "calcium dependent proteases belonging to", "dependent proteases belonging to the", "proteases belonging to the metzincin", "belonging to the metzincin family.", "to the metzincin family. they", "the metzincin family. they contain", "metzincin family. they contain a", "family. they contain a characteristic", "they contain a characteristic zinc", "contain a characteristic zinc binding", "a characteristic zinc binding motif", "characteristic zinc binding motif hexxhxxgxxh", "binding motif hexxhxxgxxh stocker", "motif hexxhxxgxxh stocker &", "hexxhxxgxxh stocker & bode", "& bode 1995 and", "bode 1995 and a", "1995 and a conserved", "and a conserved methionine which", "a conserved methionine which forms", "conserved methionine which forms a", "methionine which forms a met", "which forms a met turn.", "forms a met turn. humans", "a met turn. humans have", "met turn. humans have 24", "turn. humans have 24 mmp", "humans have 24 mmp genes", "have 24 mmp genes giving", "24 mmp genes giving rise", "mmp genes giving rise to", "genes giving rise to 23", "giving rise to 23 mmp", "rise to 23 mmp proteins", "23 mmp proteins as", "mmp proteins as mmp23", "proteins as mmp23 is", "as mmp23 is encoded by", "mmp23 is encoded by two", "is encoded by two identical", "encoded by two identical genes.", "by two identical genes. all", "two identical genes. all mmps", "identical genes. all mmps contain", "genes. all mmps contain an", "all mmps contain an n", "mmps contain an n terminal", "contain an n terminal secretory", "an n terminal secretory signal", "n terminal secretory signal peptide", "terminal secretory signal peptide and", "secretory signal peptide and a", "signal peptide and a prodomain", "peptide and a prodomain with", "and a prodomain with a", "a prodomain with a conserved", "prodomain with a conserved prcgxpd", "with a conserved prcgxpd motif", "a conserved prcgxpd motif that", "conserved prcgxpd motif that in", "prcgxpd motif that in the", "motif that in the inactive", "that in the inactive enzyme", "in the inactive enzyme is", "the inactive enzyme is localized", "inactive enzyme is localized with", "enzyme is localized with the", "is localized with the catalytic", "localized with the catalytic site", "the catalytic site the", "catalytic site the cysteine", "site the cysteine acting", "the cysteine acting as a", "cysteine acting as a fourth", "acting as a fourth unpaired", "as a fourth unpaired ligand", "a fourth unpaired ligand for", "fourth unpaired ligand for the", "unpaired ligand for the catalytic", "ligand for the catalytic zinc", "for the catalytic zinc atom.", "the catalytic zinc atom. activation", "catalytic zinc atom. activation involves", "zinc atom. activation involves delocalization", "atom. activation involves delocalization of", "activation involves delocalization of the", "involves delocalization of the domain", "delocalization of the domain containing", "of the domain containing this", "the domain containing this cysteine", "domain containing this cysteine by", "containing this cysteine by a", "this cysteine by a conformational", "cysteine by a conformational change", "by a conformational change or", "a conformational change or proteolytic", "conformational change or proteolytic cleavage", "or proteolytic cleavage a", "proteolytic cleavage a mechanism", "cleavage a mechanism referred", "a mechanism referred to as", "mechanism referred to as the", "referred to as the cysteine", "to as the cysteine switch", "the cysteine switch van", "cysteine switch van wart", "switch van wart &", "van wart & birkedal hansen", "wart & birkedal hansen 1990", "& birkedal hansen 1990 .", "hansen 1990 . most", "1990 . most mmps", ". most mmps are", "most mmps are secreted but", "mmps are secreted but the", "are secreted but the membrane", "secreted but the membrane type", "but the membrane type mt", "the membrane type mt mmps", "membrane type mt mmps are", "type mt mmps are membrane", "mt mmps are membrane anchored", "mmps are membrane anchored and", "are membrane anchored and some", "membrane anchored and some mmps", "anchored and some mmps may", "and some mmps may act", "some mmps may act on", "mmps may act on intracellular", "may act on intracellular proteins.", "act on intracellular proteins. various", "on intracellular proteins. various domains", "intracellular proteins. various domains determine", "proteins. various domains determine substrate", "various domains determine substrate specificity", "determine substrate specificity cell", "substrate specificity cell localization", "specificity cell localization and", "localization and activation hadler", "and activation hadler olsen", "activation hadler olsen et", "hadler olsen et al. 2011", "olsen et al. 2011 .", "et al. 2011 . mmps", "al. 2011 . mmps are", "2011 . mmps are regulated", ". mmps are regulated by", "mmps are regulated by transcription", "regulated by transcription cellular", "by transcription cellular location", "cellular location most are", "location most are not", "most are not activated until", "are not activated until secreted", "until secreted activating", "secreted activating proteinases", "activating proteinases that can be", "proteinases that can be other", "that can be other mmps", "be other mmps and", "other mmps and by", "mmps and by metalloproteinase", "and by metalloproteinase inhibitors such", "by metalloproteinase inhibitors such as", "metalloproteinase inhibitors such as the", "inhibitors such as the tissue", "such as the tissue inhibitors", "as the tissue inhibitors of", "the tissue inhibitors of metalloproteinases", "inhibitors of metalloproteinases timps", "of metalloproteinases timps .", "metalloproteinases timps . mmps", "timps . mmps are best", ". mmps are best known", "mmps are best known for", "are best known for their", "best known for their role", "known for their role in", "for their role in the", "their role in the degradation", "role in the degradation and", "in the degradation and removal", "the degradation and removal of", "degradation and removal of ecm", "and removal of ecm molecules.", "removal of ecm molecules. in", "of ecm molecules. in addition", "molecules. in addition cleavage", "in addition cleavage of", "addition cleavage of the", "cleavage of the ecm and", "of the ecm and other", "the ecm and other cell", "ecm and other cell surface", "and other cell surface molecules", "other cell surface molecules can", "cell surface molecules can release", "surface molecules can release ecm", "molecules can release ecm bound", "can release ecm bound growth", "release ecm bound growth factors", "bound growth factors and", "growth factors and a", "factors and a number", "and a number of non", "a number of non ecm", "number of non ecm proteins", "of non ecm proteins are", "non ecm proteins are substrates", "ecm proteins are substrates of", "proteins are substrates of mmps", "substrates of mmps nagase", "of mmps nagase et", "mmps nagase et al.", "nagase et al. 2006 .", "et al. 2006 . mmps", "al. 2006 . mmps can", "2006 . mmps can be", ". mmps can be divided", "mmps can be divided into", "can be divided into subgroups", "be divided into subgroups based", "divided into subgroups based on", "into subgroups based on domain", "subgroups based on domain structure", "based on domain structure and", "on domain structure and substrate", "domain structure and substrate specificity", "structure and substrate specificity but", "and substrate specificity but it", "substrate specificity but it is", "specificity but it is clear", "but it is clear that", "it is clear that these", "is clear that these are", "clear that these are somewhat", "that these are somewhat artificial", "are somewhat artificial many", "somewhat artificial many mmps", "artificial many mmps belong", "many mmps belong to more", "mmps belong to more than", "belong to more than one", "to more than one functional", "more than one functional group", "one functional group vise", "functional group vise &", "group vise & nagase", "& nagase 2003 somerville", "nagase 2003 somerville et", "2003 somerville et al.", "somerville et al. 2003 ." ] }, { "record_id": "GLY_000594_1_60", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1482925", "r hsa", "hsa 1482925", "r hsa 1482925" ] }, { "record_id": "GLY_000594_1_60", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acyl chain", "chain remodelling", "remodelling of", "of pg", "acyl chain remodelling", "chain remodelling of", "remodelling of pg", "acyl chain remodelling of", "chain remodelling of pg", "acyl chain remodelling of pg", "in the", "the acyl", "remodelling pathway", "lands cycle", "is hydrolyzed", "hydrolyzed by", "by phopholipases", "phopholipases and", "and subsequently", "subsequently reacylated", "reacylated by", "by acyltransferases.", "these cycles", "cycles modify", "modify the", "the fatty", "fatty acid", "acid composition", "composition of", "of glycerophospholipids", "glycerophospholipids to", "to generate", "generate diverse", "diverse molecules", "molecules asymmetrically", "asymmetrically distributed", "distributed in", "the cell", "cell membrane.", "the events", "events occur", "occur additionally", "additionally in", "the inner", "inner mitochondria", "mitochondria membranes", "as well", "well as", "as in", "the endoplasmic", "endoplasmic reticulum", "ghomashchi et", "et al.", "al. 2010", "singer et", "al. 2002", "cao et", "al. 2008", "yang et", "al. 2004", "nie et", "2010 .", "in the acyl", "the acyl chain", "chain remodelling pathway", "pathway lands", "phosphatidylglycerol pg", "pg is", "is hydrolyzed by", "hydrolyzed by phopholipases", "by phopholipases and", "phopholipases and subsequently", "and subsequently reacylated", "subsequently reacylated by", "reacylated by acyltransferases.", "acyltransferases. these", "these cycles modify", "cycles modify the", "modify the fatty", "the fatty acid", "fatty acid composition", "acid composition of", "composition of glycerophospholipids", "of glycerophospholipids to", "glycerophospholipids to generate", "to generate diverse", "generate diverse molecules", "diverse molecules asymmetrically", "molecules asymmetrically distributed", "asymmetrically distributed in", "distributed in the", "in the cell", "the cell membrane.", "membrane. the", "the events occur", "events occur additionally", "occur additionally in", "additionally in the", "in the inner", "the inner mitochondria", "inner mitochondria membranes", "membranes im", "im as", "as well as", "well as in", "as in the", "in the endoplasmic", "the endoplasmic reticulum", "reticulum er", "er membrane", "membrane ghomashchi", "ghomashchi et al.", "et al. 2010", "2010 singer", "singer et al.", "et al. 2002", "2002 cao", "cao et al.", "et al. 2008", "2008 yang", "yang et al.", "et al. 2004", "2004 nie", "nie et al.", "al. 2010 .", "in the acyl chain", "the acyl chain remodelling", "acyl chain remodelling pathway", "remodelling pathway lands", "pathway lands cycle", "cycle phosphatidylglycerol", "pg is hydrolyzed", "is hydrolyzed by phopholipases", "hydrolyzed by phopholipases and", "by phopholipases and subsequently", "phopholipases and subsequently reacylated", "and subsequently reacylated by", "subsequently reacylated by acyltransferases.", "by acyltransferases. these", "acyltransferases. these cycles", "these cycles modify the", "cycles modify the fatty", "modify the fatty acid", "the fatty acid composition", "fatty acid composition of", "acid composition of glycerophospholipids", "composition of glycerophospholipids to", "of glycerophospholipids to generate", "glycerophospholipids to generate diverse", "to generate diverse molecules", "generate diverse molecules asymmetrically", "diverse molecules asymmetrically distributed", "molecules asymmetrically distributed in", "asymmetrically distributed in the", "distributed in the cell", "in the cell membrane.", "cell membrane. the", "membrane. the events", "the events occur additionally", "events occur additionally in", "occur additionally in the", "additionally in the inner", "in the inner mitochondria", "the inner mitochondria membranes", "mitochondria membranes im", "im as well", "as well as in", "well as in the", "as in the endoplasmic", "in the endoplasmic reticulum", "endoplasmic reticulum er", "membrane ghomashchi et", "ghomashchi et al. 2010", "al. 2010 singer", "2010 singer et", "singer et al. 2002", "al. 2002 cao", "2002 cao et", "cao et al. 2008", "al. 2008 yang", "2008 yang et", "yang et al. 2004", "al. 2004 nie", "2004 nie et", "nie et al. 2010", "et al. 2010 .", "in the acyl chain remodelling", "the acyl chain remodelling pathway", "chain remodelling pathway lands", "remodelling pathway lands cycle", "lands cycle phosphatidylglycerol", "phosphatidylglycerol pg is", "pg is hydrolyzed by", "is hydrolyzed by phopholipases and", "hydrolyzed by phopholipases and subsequently", "by phopholipases and subsequently reacylated", "phopholipases and subsequently reacylated by", "and subsequently reacylated by acyltransferases.", "reacylated by acyltransferases. these", "by acyltransferases. these cycles", "acyltransferases. these cycles modify", "these cycles modify the fatty", "cycles modify the fatty acid", "modify the fatty acid composition", "the fatty acid composition of", "fatty acid composition of glycerophospholipids", "acid composition of glycerophospholipids to", "composition of glycerophospholipids to generate", "of glycerophospholipids to generate diverse", "glycerophospholipids to generate diverse molecules", "to generate diverse molecules asymmetrically", "generate diverse molecules asymmetrically distributed", "diverse molecules asymmetrically distributed in", "molecules asymmetrically distributed in the", "asymmetrically distributed in the cell", "distributed in the cell membrane.", "the cell membrane. the", "cell membrane. the events", "membrane. the events occur", "the events occur additionally in", "events occur additionally in the", "occur additionally in the inner", "additionally in the inner mitochondria", "in the inner mitochondria membranes", "inner mitochondria membranes im", "membranes im as", "im as well as", "as well as in the", "well as in the endoplasmic", "as in the endoplasmic reticulum", "the endoplasmic reticulum er", "reticulum er membrane", "er membrane ghomashchi", "membrane ghomashchi et al.", "et al. 2010 singer", "al. 2010 singer et", "2010 singer et al.", "et al. 2002 cao", "al. 2002 cao et", "2002 cao et al.", "et al. 2008 yang", "al. 2008 yang et", "2008 yang et al.", "et al. 2004 nie", "al. 2004 nie et", "2004 nie et al.", "nie et al. 2010 ." ] }, { "record_id": "GLY_000594_1_61", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483148", "r hsa", "hsa 1483148", "r hsa 1483148" ] }, { "record_id": "GLY_000594_1_61", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pg", "synthesis of pg", "is synthesised", "synthesised at", "at the", "the inner", "inner mitochondrial", "phosphatidic acid", "and cytidine", "cytidine triphosphate", "are converted", "converted into", "into cytidine", "cytidine diphosphate", "diphosphate diacylglycerol", "cdp dag", "which in", "in turn", "turn is", "is converted", "converted with", "with glycerol", "glycerol 3", "3 phosphate", "into phosphatidylglycerophosphate", "cytidine monophosphate", "cmp .", "pgp is", "is dephosphorylated", "dephosphorylated to", "to pg.", "in addition", "pg can", "can be", "be synthesised", "the endoplamic", "endoplamic reticulum", "membrane when", "when phospholipase", "phospholipase d", "d transphosphatidylates", "transphosphatidylates phosphatidylcholine", "glycerol to", "to displace", "displace choline", "and form", "form pg", "piazza &", "& marmer", "marmer 2007", "stuhne sekalec", "sekalec et", "et al.", "al. 1986", "lykidis et", "al. 1997", "cao &", "& hatch", "hatch 1994", "1994 .", "phosphatidylglycerol pg", "pg is", "is synthesised at", "synthesised at the", "at the inner", "the inner mitochondrial", "mitochondrial im", "im membrane", "membrane phosphatidic", "acid pa", "pa and", "and cytidine triphosphate", "triphosphate ctp", "ctp are", "are converted into", "converted into cytidine", "into cytidine diphosphate", "cytidine diphosphate diacylglycerol", "diacylglycerol cdp", "which in turn", "in turn is", "turn is converted", "is converted with", "converted with glycerol", "with glycerol 3", "glycerol 3 phosphate", "phosphate g3p", "g3p into", "phosphatidylglycerophosphate pgp", "pgp and", "and cytidine monophosphate", "monophosphate cmp", ". finally", "finally pgp", "pgp is dephosphorylated", "is dephosphorylated to", "dephosphorylated to pg.", "pg. in", "addition pg", "pg can be", "can be synthesised", "be synthesised at", "at the endoplamic", "the endoplamic reticulum", "reticulum er", "er membrane", "membrane when phospholipase", "when phospholipase d", "phospholipase d transphosphatidylates", "d transphosphatidylates phosphatidylcholine", "phosphatidylcholine pc", "pc with", "with glycerol to", "glycerol to displace", "to displace choline", "choline cho", "cho and", "and form pg", "pg piazza", "piazza & marmer", "& marmer 2007", "2007 stuhne", "stuhne sekalec et", "sekalec et al.", "et al. 1986", "1986 lykidis", "lykidis et al.", "et al. 1997", "1997 cao", "cao & hatch", "& hatch 1994", "hatch 1994 .", "pg is synthesised", "is synthesised at the", "synthesised at the inner", "at the inner mitochondrial", "inner mitochondrial im", "membrane phosphatidic acid", "phosphatidic acid pa", "pa and cytidine", "cytidine triphosphate ctp", "ctp are converted", "are converted into cytidine", "converted into cytidine diphosphate", "into cytidine diphosphate diacylglycerol", "diphosphate diacylglycerol cdp", "diacylglycerol cdp dag", "dag which", "which in turn is", "in turn is converted", "turn is converted with", "is converted with glycerol", "converted with glycerol 3", "with glycerol 3 phosphate", "3 phosphate g3p", "g3p into phosphatidylglycerophosphate", "into phosphatidylglycerophosphate pgp", "pgp and cytidine", "cytidine monophosphate cmp", "monophosphate cmp .", "cmp . finally", "finally pgp is", "pgp is dephosphorylated to", "is dephosphorylated to pg.", "to pg. in", "pg. in addition", "in addition pg", "addition pg can", "pg can be synthesised", "can be synthesised at", "be synthesised at the", "synthesised at the endoplamic", "at the endoplamic reticulum", "endoplamic reticulum er", "er membrane when", "membrane when phospholipase d", "when phospholipase d transphosphatidylates", "phospholipase d transphosphatidylates phosphatidylcholine", "transphosphatidylates phosphatidylcholine pc", "pc with glycerol", "with glycerol to displace", "glycerol to displace choline", "displace choline cho", "cho and form", "form pg piazza", "pg piazza &", "piazza & marmer 2007", "marmer 2007 stuhne", "2007 stuhne sekalec", "stuhne sekalec et al.", "sekalec et al. 1986", "al. 1986 lykidis", "1986 lykidis et", "lykidis et al. 1997", "al. 1997 cao", "1997 cao &", "cao & hatch 1994", "& hatch 1994 .", "phosphatidylglycerol pg is", "pg is synthesised at", "is synthesised at the inner", "synthesised at the inner mitochondrial", "the inner mitochondrial im", "mitochondrial im membrane", "im membrane phosphatidic", "acid pa and", "pa and cytidine triphosphate", "and cytidine triphosphate ctp", "triphosphate ctp are", "ctp are converted into", "are converted into cytidine diphosphate", "converted into cytidine diphosphate diacylglycerol", "cytidine diphosphate diacylglycerol cdp", "diphosphate diacylglycerol cdp dag", "cdp dag which", "dag which in", "which in turn is converted", "in turn is converted with", "turn is converted with glycerol", "is converted with glycerol 3", "converted with glycerol 3 phosphate", "glycerol 3 phosphate g3p", "phosphate g3p into", "phosphatidylglycerophosphate pgp and", "pgp and cytidine monophosphate", "and cytidine monophosphate cmp", "cytidine monophosphate cmp .", ". finally pgp", "finally pgp is dephosphorylated", "pgp is dephosphorylated to pg.", "dephosphorylated to pg. in", "to pg. in addition", "in addition pg can", "addition pg can be", "pg can be synthesised at", "can be synthesised at the", "be synthesised at the endoplamic", "synthesised at the endoplamic reticulum", "the endoplamic reticulum er", "reticulum er membrane", "er membrane when phospholipase", "membrane when phospholipase d transphosphatidylates", "when phospholipase d transphosphatidylates phosphatidylcholine", "d transphosphatidylates phosphatidylcholine pc", "phosphatidylcholine pc with", "pc with glycerol to", "with glycerol to displace choline", "to displace choline cho", "choline cho and", "cho and form pg", "and form pg piazza", "form pg piazza &", "pg piazza & marmer", "& marmer 2007 stuhne", "marmer 2007 stuhne sekalec", "2007 stuhne sekalec et", "stuhne sekalec et al. 1986", "et al. 1986 lykidis", "al. 1986 lykidis et", "1986 lykidis et al.", "et al. 1997 cao", "al. 1997 cao &", "1997 cao & hatch", "cao & hatch 1994 ." ] }, { "record_id": "GLY_000594_1_62", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483166", "r hsa", "hsa 1483166", "r hsa 1483166" ] }, { "record_id": "GLY_000594_1_62", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pa", "synthesis of pa", "in the", "the de", "de novo", "novo synthesis", "of phosphatidic", "phosphatidic acid", "lysophosphatidic acid", 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rx +", "+ gsh", "> hx", "hx +", "+ gsr

glutathione", "gsr

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rx", "reaction is

rx +", "is

rx + gsh", "gsh >", "> hx +", "hx + gsr

glutathione", "+ gsr

glutathione conjugates", "gsr

glutathione conjugates are", "conjugates are excreted", "are excreted in", "excreted in bile", "in bile and", "bile and converted", "and converted to", "converted to cysteine", "to cysteine and", "cysteine and mercapturic", "and mercapturic acid", "mercapturic acid conjugates", "acid conjugates in", "conjugates in the", "in the intestine", "the intestine and", "intestine and kidneys.", "and kidneys. gsh", "kidneys. gsh is", "gsh is the", "is the major", "major low", "low molecular weight", "weight non", "non protein thiol", "protein thiol synthesized", "thiol synthesized de", "synthesized de novo", "de novo in", "novo in mammalian", "in mammalian cells.", "mammalian cells. as", "cells. as well", "well as taking", "as taking part", "taking part in", "part in conjugation", "in conjugation reactions", "reactions gsh", "gsh also has", "also has antioxidant", "has antioxidant ability", "antioxidant ability and", "ability and can", "and can metabolize", "can metabolize endogenous", "metabolize endogenous and", "and exogenous compounds.", "exogenous compounds. the", "compounds. the nucleophilic", "the nucleophilic gsh", "nucleophilic gsh attacks", "gsh attacks the", "attacks the electrophilic", "the electrophilic substrate", "electrophilic substrate forming", "substrate forming a", "forming a thioether", "a thioether bond", "thioether bond between", "bond between the", "between the cysteine", "the cysteine residue", "cysteine residue of", "residue of gsh", "of gsh and", "gsh and the", "and the electrophile.", "the electrophile. the", "electrophile. the result", "the result is", "result is generally", "is generally a", "generally a less", "a less reactive", "less reactive and", "reactive and more", "and more water", "more water soluble", "water soluble conjugate", "soluble conjugate that", "conjugate that can", "that can be", "can be easily", "be easily excreted.", "easily excreted. in", "excreted. in some", "in some cases", "cases gsts", "gsts can activate", "can activate compounds", "activate compounds to", "compounds to reactive", "to reactive species", "reactive species such", "species such as", "such as certain", "as certain haloalkanes", "certain haloalkanes and", "haloalkanes and haloalkenes.", "and haloalkenes. substrates", "haloalkenes. substrates for", "substrates for gsts", "for gsts include", "gsts include epoxides", "epoxides alkenes", "alkenes and compounds", "and compounds with", "compounds with electrophilic", "with electrophilic carbon", "carbon sulfur", "sulfur or nitrogen", "or nitrogen centres.", "nitrogen centres. there", "centres. there are", "there are two", "are two types", "two types of", "types of conjugation", "of conjugation reaction", "conjugation reaction with", "reaction with glutathione:", "with glutathione: displacement", "glutathione: displacement reactions", "displacement reactions where", "reactions where glutathione", "where glutathione displaces", "glutathione displaces an", "displaces an electron", "an electron withdrawing", "electron withdrawing group", "withdrawing group and", "group and addition", "and addition reactions", "addition reactions where", "where glutathione is", "glutathione is added", "is added to", "added to activated", "to activated double", "activated double bond", "double bond structures", "bond structures or", "structures or strained", "or strained ring", "strained ring systems.", "s transferases gsts", "gsts ec 2.5.1.18", "ec 2.5.1.18 are", "2.5.1.18 are another", "are another major set", "another major set of", "major set of phase", "set of phase ii", "of phase ii conjugation", "phase ii conjugation enzymes.", "ii conjugation enzymes. they", "conjugation enzymes. they can", "enzymes. they can be", "they can be found", "can be found in", "be found in the", "found in the cytosol", "in the cytosol as", "the cytosol as well", "cytosol as well as", "as well as being", "well as being microsomal", "as being microsomal membrane", "being microsomal membrane bound.", "microsomal membrane bound. cytosolic", "membrane bound. cytosolic gsts", "bound. cytosolic gsts are", "cytosolic gsts are encoded", "gsts are encoded by", "are encoded by at", "encoded by at least", "by at least 5", "at least 5 gene", "least 5 gene families", "gene families alpha", "theta and zeta", "zeta gst whereas", "gst whereas membrane", "whereas membrane bound enzymes", "membrane bound enzymes are", "bound enzymes are encoded", "enzymes are encoded by", "are encoded by single", "encoded by single genes.", "by single genes. soluble", "single genes. soluble gsts", "genes. soluble gsts are", "soluble gsts are homo", "are homo or", "homo or hetero", "or hetero dimeric enzymes", "dimeric enzymes approximately", "enzymes approximately 25kda", "25kda subunits which", "subunits which can", "which can act on", "can act on a", "act on a wide", "on a wide range", "a wide range of", "wide range of endogenous", "range of endogenous and", "of endogenous and exogenous", "and exogenous electrophiles.", "exogenous electrophiles. gsts", "electrophiles. gsts mediate conjugation", "gsts mediate conjugation using", "mediate conjugation using glutathione", "using glutathione gsh", "gsh a", "a tripeptide synthesized from", "tripeptide synthesized from its", "synthesized from its precursor", "from its precursor amino", "its precursor amino acids", "precursor amino acids gamma", "amino acids gamma glutamate", "gamma glutamate cysteine", "glutamate cysteine and", "cysteine and glycine. a", "and glycine. a generalized", "glycine. a generalized reaction", "a generalized reaction is

rx", "generalized reaction is

rx +", "reaction is

rx + gsh", "+ gsh >", "gsh > hx", "> hx + gsr

glutathione", "hx + gsr

glutathione conjugates", "+ gsr

glutathione conjugates are", "gsr

glutathione conjugates are excreted", "conjugates are excreted in", "are excreted in bile", "excreted in bile and", "in bile and converted", "bile and converted to", "and converted to cysteine", "converted to cysteine and", "to cysteine and mercapturic", "cysteine and mercapturic acid", "and mercapturic acid conjugates", "mercapturic acid conjugates in", "acid conjugates in the", "conjugates in the intestine", "in the intestine and", "the intestine and kidneys.", "intestine and kidneys. gsh", "and kidneys. gsh is", "kidneys. gsh is the", "gsh is the major", "the major low", "major low molecular", "molecular weight non", "weight non protein", "non protein thiol synthesized", "protein thiol synthesized de", "thiol synthesized de novo", "synthesized de novo in", "de novo in mammalian", "novo in mammalian cells.", "in mammalian cells. as", "mammalian cells. as well", "cells. as well as", "as well as taking", "well as taking part", "as taking part in", "taking part in conjugation", "part in conjugation reactions", "conjugation reactions gsh", "reactions gsh also", "gsh also has antioxidant", "also has antioxidant ability", "has antioxidant ability and", "antioxidant ability and can", "ability and can metabolize", "and can metabolize endogenous", "can metabolize endogenous and", "metabolize endogenous and exogenous", "endogenous and exogenous compounds.", "and exogenous compounds. the", "exogenous compounds. the nucleophilic", "compounds. the nucleophilic gsh", "the nucleophilic gsh attacks", "nucleophilic gsh attacks the", "gsh attacks the electrophilic", "attacks the electrophilic substrate", "the electrophilic substrate forming", "electrophilic substrate forming a", "substrate forming a thioether", "forming a thioether bond", "a thioether bond between", "thioether bond between the", "bond between the cysteine", "between the cysteine residue", "the cysteine residue of", "cysteine residue of gsh", "residue of gsh and", "of gsh and the", "gsh and the electrophile.", "and the electrophile. the", "the electrophile. the result", "electrophile. the result is", "the result is generally", "result is generally a", "is generally a less", "generally a less reactive", "a less reactive and", "less reactive and more", "reactive and more water", "and more water soluble", "more water soluble conjugate", "water soluble conjugate that", "soluble conjugate that can", "conjugate that can be", "that can be easily", "can be easily excreted.", "be easily excreted. in", "easily excreted. in some", "excreted. in some cases", "some cases gsts", "cases gsts can", "gsts can activate compounds", "can activate compounds to", "activate compounds to reactive", "compounds to reactive species", "to reactive species such", "reactive species such as", "species such as certain", "such as certain haloalkanes", "as certain haloalkanes and", "certain haloalkanes and haloalkenes.", "haloalkanes and haloalkenes. substrates", "and haloalkenes. substrates for", "haloalkenes. substrates for gsts", "substrates for gsts include", "for gsts include epoxides", "include epoxides alkenes", "epoxides alkenes and", "alkenes and compounds with", "and compounds with electrophilic", "compounds with electrophilic carbon", "electrophilic carbon sulfur", "carbon sulfur or", "sulfur or nitrogen centres.", "or nitrogen centres. there", "nitrogen centres. there are", "centres. there are two", "there are two types", "are two types of", "two types of conjugation", "types of conjugation reaction", "of conjugation reaction with", "conjugation reaction with glutathione:", "reaction with glutathione: displacement", "with glutathione: displacement reactions", "glutathione: displacement reactions where", "displacement reactions where glutathione", "reactions where glutathione displaces", "where glutathione displaces an", "glutathione displaces an electron", "displaces an electron withdrawing", "an electron withdrawing group", "electron withdrawing group and", "withdrawing group and addition", "group and addition reactions", "and addition reactions where", "addition reactions where glutathione", "reactions where glutathione is", "where glutathione is added", "glutathione is added to", "is added to activated", "added to activated double", "to activated double bond", "activated double bond structures", "double bond structures or", "bond structures or strained", "structures or strained ring", "or strained ring systems.", "glutathione s transferases gsts", "transferases gsts ec", "ec 2.5.1.18 are another", "2.5.1.18 are another major", "are another major set of", "another major set of phase", "major set of phase ii", "set of phase ii conjugation", "of phase ii conjugation enzymes.", "phase ii conjugation enzymes. they", "ii conjugation enzymes. they can", "conjugation enzymes. they can be", "enzymes. they can be found", "they can be found in", "can be found in the", "be found in the cytosol", "found in the cytosol as", "in the cytosol as well", "the cytosol as well as", "cytosol as well as being", "as well as being microsomal", "well as being microsomal membrane", "as being microsomal membrane bound.", "being microsomal membrane bound. cytosolic", "microsomal membrane bound. cytosolic gsts", "membrane bound. cytosolic gsts are", "bound. cytosolic gsts are encoded", "cytosolic gsts are encoded by", "gsts are encoded by at", "are encoded by at least", "encoded by at least 5", "by at least 5 gene", "at least 5 gene families", "5 gene families alpha", "families alpha mu", "alpha mu pi", "mu pi theta", "pi theta and", "theta and zeta gst", "and zeta gst whereas", "zeta gst whereas membrane", "gst whereas membrane bound", "whereas membrane bound enzymes are", "membrane bound enzymes are encoded", "bound enzymes are encoded by", "enzymes are encoded by single", "are encoded by single genes.", "encoded by single genes. soluble", "by single genes. soluble gsts", "single genes. soluble gsts are", "genes. soluble gsts are homo", "gsts are homo or", "are homo or hetero", "homo or hetero dimeric", "hetero dimeric enzymes approximately", "dimeric enzymes approximately 25kda", "enzymes approximately 25kda subunits", "approximately 25kda subunits which", "25kda subunits which can", "subunits which can act", "which can act on a", "can act on a wide", "act on a wide range", "on a wide range of", "a wide range of endogenous", "wide range of endogenous and", "range of endogenous and exogenous", "endogenous and exogenous electrophiles.", "and exogenous electrophiles. gsts", "exogenous electrophiles. gsts mediate", "electrophiles. gsts mediate conjugation using", "gsts mediate conjugation using glutathione", "conjugation using glutathione gsh", "gsh a tripeptide", "a tripeptide synthesized from its", "tripeptide synthesized from its precursor", "synthesized from its precursor amino", "from its precursor amino acids", "its precursor amino acids gamma", "precursor amino acids gamma glutamate", "acids gamma glutamate cysteine", "gamma glutamate cysteine and", "glutamate cysteine and glycine.", "cysteine and glycine. a generalized", "and glycine. a generalized reaction", "glycine. a generalized reaction is

rx", "a generalized reaction is

rx +", "generalized reaction is

rx + gsh", "is

rx + gsh >", "+ gsh > hx", "gsh > hx +", "> hx + gsr

glutathione conjugates", "hx + gsr

glutathione conjugates are", "+ gsr

glutathione conjugates are excreted", "gsr

glutathione conjugates are excreted in", "conjugates are excreted in bile", "are excreted in bile and", "excreted in bile and converted", "in bile and converted to", "bile and converted to cysteine", "and converted to cysteine and", "converted to cysteine and mercapturic", "to cysteine and mercapturic acid", "cysteine and mercapturic acid conjugates", "and mercapturic acid conjugates in", "mercapturic acid conjugates in the", "acid conjugates in the intestine", "conjugates in the intestine and", "in the intestine and kidneys.", "the intestine and kidneys. gsh", "intestine and kidneys. gsh is", "and kidneys. gsh is the", "kidneys. gsh is the major", "is the major low", "the major low molecular", "major low molecular weight", "low molecular weight non", "molecular weight non protein", "weight non protein thiol", "non protein thiol synthesized de", "protein thiol synthesized de novo", "thiol synthesized de novo in", "synthesized de novo in mammalian", "de novo in mammalian cells.", "novo in mammalian cells. as", "in mammalian cells. as well", "mammalian cells. as well as", "cells. as well as taking", "as well as taking part", "well as taking part in", "as taking part in conjugation", "taking part in conjugation reactions", "in conjugation reactions gsh", "conjugation reactions gsh also", "reactions gsh also has", "gsh also has antioxidant ability", "also has antioxidant ability and", "has antioxidant ability and can", "antioxidant ability and can metabolize", "ability and can metabolize endogenous", "and can metabolize endogenous and", "can metabolize endogenous and exogenous", "metabolize endogenous and exogenous compounds.", "endogenous and exogenous compounds. the", "and exogenous compounds. the nucleophilic", "exogenous compounds. the nucleophilic gsh", "compounds. the nucleophilic gsh attacks", "the nucleophilic gsh attacks the", "nucleophilic gsh attacks the electrophilic", "gsh attacks the electrophilic substrate", "attacks the electrophilic substrate forming", "the electrophilic substrate forming a", "electrophilic substrate forming a thioether", "substrate forming a thioether bond", "forming a thioether bond between", "a thioether bond between the", "thioether bond between the cysteine", "bond between the cysteine residue", "between the cysteine residue of", "the cysteine residue of gsh", "cysteine residue of gsh and", "residue of gsh and the", "of gsh and the electrophile.", "gsh and the electrophile. the", "and the electrophile. the result", "the electrophile. the result is", "electrophile. the result is generally", "the result is generally a", "result is generally a less", "is generally a less reactive", "generally a less reactive and", "a less reactive and more", "less reactive and more water", "reactive and more water soluble", "and more water soluble conjugate", "more water soluble conjugate that", "water soluble conjugate that can", "soluble conjugate that can be", "conjugate that can be easily", "that can be easily excreted.", "can be easily excreted. in", "be easily excreted. in some", "easily excreted. in some cases", "in some cases gsts", "some cases gsts can", "cases gsts can activate", "gsts can activate compounds to", "can activate compounds to reactive", "activate compounds to reactive species", "compounds to reactive species such", "to reactive species such as", "reactive species such as certain", "species such as certain haloalkanes", "such as certain haloalkanes and", "as certain haloalkanes and haloalkenes.", "certain haloalkanes and haloalkenes. substrates", "haloalkanes and haloalkenes. substrates for", "and haloalkenes. substrates for gsts", "haloalkenes. substrates for gsts include", "substrates for gsts include epoxides", "gsts include epoxides alkenes", "include epoxides alkenes and", "epoxides alkenes and compounds", "alkenes and compounds with electrophilic", "and compounds with electrophilic carbon", "with electrophilic carbon sulfur", "electrophilic carbon sulfur or", "carbon sulfur or nitrogen", "sulfur or nitrogen centres. there", "or nitrogen centres. there are", "nitrogen centres. there are two", "centres. there are two types", "there are two types of", "are two types of conjugation", "two types of conjugation reaction", "types of conjugation reaction with", "of conjugation reaction with glutathione:", "conjugation reaction with glutathione: displacement", "reaction with glutathione: displacement reactions", "with glutathione: displacement reactions where", "glutathione: displacement reactions where glutathione", "displacement reactions where glutathione displaces", "reactions where glutathione displaces an", "where glutathione displaces an electron", "glutathione displaces an electron withdrawing", "displaces an electron withdrawing group", "an electron withdrawing group and", "electron withdrawing group and addition", "withdrawing group and addition reactions", "group and addition reactions where", "and addition reactions where glutathione", "addition reactions where glutathione is", "reactions where glutathione is added", "where glutathione is added to", "glutathione is added to activated", "is added to activated double", "added to activated double bond", "to activated double bond structures", "activated double bond structures or", "double bond structures or strained", "bond structures or strained ring", "structures or strained ring systems." ] }, { "record_id": "GLY_000594_1_66", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "156827", "r hsa", "hsa 156827", "r hsa 156827" ] }, { "record_id": "GLY_000594_1_66", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "l13a mediated", "mediated translational", "translational silencing", "silencing of", "of ceruloplasmin", "ceruloplasmin expression", "l13a mediated translational", "mediated translational silencing", "translational silencing of", "silencing of ceruloplasmin", "of ceruloplasmin expression", "l13a mediated translational silencing", "mediated translational silencing of", "translational silencing of ceruloplasmin", "silencing of ceruloplasmin expression", "l13a mediated translational silencing of", "mediated translational silencing of ceruloplasmin", "translational silencing of ceruloplasmin expression", "while circularization", "circularization of", "of mrna", "mrna during", "during translation", "translation initiation", "initiation is", "is thought", "thought to", "to contribute", "contribute to", "to an", "an increase", "increase in", "in the", "the efficiency", "efficiency of", "of translation", "it also", "also appears", "appears to", "to provide", "provide a", "a mechanism", "mechanism for", "for translational", "translational silencing.", "silencing. this", "this might", "might be", "be achieved", "achieved by", "by bringing", "bringing inhibitory", "inhibitory 3'", "3' utr", "utr binding", "binding proteins", "proteins into", "into a", "a position", "position in", "in which", "which they", "they interfere", "interfere either", "either with", "with the", "the function", "function of", "of the", "the translation", "initiation complex", "complex or", "or with", "the assembly", "assembly of", "the ribosome", "mazumder et", "et al", "al 2001", "2001 .", "occurs 16", "16 hrs", "hrs after", "after its", "its induction", "induction by", "by inf", "inf gamma", "et al.", "1997 .", ". although", "although the", "the mechanism", "mechanism by", "by which", "which silencing", "silencing occurs", "occurs has", "has not", "not yet", "yet been", "been determined", "this process", "process is", "is mediated", "mediated by", "by the", "the l13a", "subunit of", "the 60s", "60s ribosome", "ribosome and", "to require", "require circularization", "the cp", "cp mrna", "sampath et", "2003 .", ". between", "between 14", "14 and", "and 16", "after inf", "gamma induction", "l13a subunit", "ribosome is", "is phosphorylated", "phosphorylated and", "and released", "released from", "from the", "60s subunit.", "subunit. phosphorylated", "phosphorylated l13a", "l13a then", "then associates", "associates with", "the gait", "gait element", "element in", "the 3'", "utr of", "mrna inhibiting", "inhibiting its", "its translation.", "while circularization of", "circularization of mrna", "of mrna during", "mrna during translation", "during translation initiation", "translation initiation is", "initiation is thought", "is thought to", "thought to contribute", "to contribute to", "contribute to an", "to an increase", "an increase in", "increase in the", "in the efficiency", "the efficiency of", "efficiency of translation", "translation it", "it also appears", "also appears to", "appears to provide", "to provide a", "provide a mechanism", "a mechanism for", "mechanism for translational", "for translational silencing.", "translational silencing. this", "silencing. this might", "this might be", "might be achieved", "be achieved by", "achieved by bringing", "by bringing 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the", ".

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despite", "

despite the", "the undoubted", "undoubted importance", "importance of", "these reactions", "reactions in", "in normal", "normal human", "human energy", "energy metabolism", "metabolism and", "and in", "the pathology", "pathology of", "of diseases", "diseases such", "such as", "as type", "type ii", "ii diabetes", "they have", "have been", "been studied", "studied only", "only to", "to a", "a limited", "limited extent", "extent in", "in human", "human cells", "cells and", "and tissues.", "tissues. most", "most experimental", "experimental data", "data are", "are derived", "derived instead", "instead from", "from two", "two rodent", "rodent model", "model systems:", "systems: primary", "primary adipocytes", "adipocytes from", "from rats", "and mouse", "mouse 3t3", "3t3 l1", "l1 cells", "cells induced", "induced to", "to differentiate", "differentiate into", "into adipocytes.", "triacylglycerol is a", "is a major", "a major energy", "major energy store", "energy store in", "store in the", "in the body", "the body and", "body and its", "and its hydrolysis", "its hydrolysis to", "hydrolysis to yield", "to yield fatty", "yield fatty acids", "fatty acids and", "acids and glycerol", "and glycerol is", "glycerol is a", "is a tightly", "a tightly regulated", "tightly regulated part", "regulated part of", "part of energy", "of energy metabolism.", "energy metabolism. a", "metabolism. a central", "a central part", "central part in", "part in this", "in this regulation", "this regulation is", "regulation is played", "is played by", "played by hormone", "by hormone sensitive", "hormone sensitive lipase", "lipase hsl", "a neutral lipase", "neutral lipase abundant", "lipase abundant in", "abundant in adipocytes", "in adipocytes and", "adipocytes and skeletal", "and skeletal and", "skeletal and cardiac", "and cardiac muscle", "muscle but", "but also abundant", "also abundant in", "abundant in ovarian", "in ovarian and", "ovarian and adrenal", "and adrenal tissue", "tissue where", "where it mediates", "it mediates cholesterol", "mediates cholesterol ester", "cholesterol ester hydrolysis", "hydrolysis yielding", "yielding cholesterol for", "cholesterol for steroid", "for steroid biosynthesis.", "steroid biosynthesis. the", "biosynthesis. the hormones", "the hormones to", "hormones to which", "to which it", "which it is", "it is sensitive", "is sensitive include", "sensitive include catecholamines", "catecholamines e.g.", "e.g. epinephrine", "acth and", "glucagon all", "all of which", "of which trigger", "which trigger signaling", "trigger signaling cascades", "signaling cascades that", "cascades that lead", "that lead to", "lead to its", "to its phosphorylation", "its phosphorylation and", "phosphorylation and activation", "activation and", "insulin which", "which sets off", "sets off events", "off events leading", "events leading to", "leading to its", "to its dephosphorylation", "its dephosphorylation and", "dephosphorylation and inactivation", "inactivation holm", "holm et al.", "et al. 2000", "2000 kraemer", "kraemer and shen", "and shen 2002", "shen 2002 .

the", "2002 .

the processes", ".

the processes of", "processes of triacylglycerol", "of triacylglycerol and", "triacylglycerol and cholesterol", "and cholesterol ester", "ester hydrolysis are", "hydrolysis are also", "are also regulated", "also regulated by", "regulated by subcellular", "by subcellular compartmentalization:", "subcellular compartmentalization: these", "compartmentalization: these lipids", "these lipids are", "lipids are packaged", "are packaged in", "packaged in cytosolic", "in cytosolic particles", "cytosolic particles and", "particles and the", "and the enzymes", "the enzymes responsible", "enzymes responsible for", "responsible for their", "for their hydrolysis", "hydrolysis and", "and perhaps for", "perhaps for additional", "for additional steps", "additional steps in", "steps in their", "in their metabolism", "metabolism are", "are organized at", "organized at the", "at the surfaces", "the surfaces of", "surfaces of these", "of these particles", "particles e.g.", "e.g. brasaemle", "brasaemle et al.", "et al. 2004", "al. 2004 .", "2004 . this", ". this organization", "this organization is", "organization is dynamic:", "is dynamic: the", "dynamic: the inactive", "the inactive form", "inactive form of", "form of hsl", "of hsl is", "hsl is not", "is not associated", "not associated with", "associated with the", "with the particles", "particles but", "but is translocated", "is translocated there", "translocated there after", "there after being", "after being phosphorylated.", "being phosphorylated. conversely", "conversely perilipin", "perilipin a", "a major constituent", "major constituent of", "constituent of the", "of the particle", "the particle surface", "surface appears", "appears to block", "to block access", "block access of", "access of enzymes", "of enzymes to", "enzymes to the", "to the lipids", "the lipids within", "lipids within the", "within the particle", "particle its", "its phosphorylation allows", "phosphorylation allows greater", "allows greater access.", "greater access.

here", "

here hsl", "hsl mediated triacylglycerol", "mediated triacylglycerol hydrolysis", "triacylglycerol hydrolysis is", "hydrolysis is described", "is described as", "described as a", "as a pathway", "a pathway containing", "pathway containing twelve", "containing twelve reactions.", "twelve reactions. the", "reactions. the first", "the first six", "first six of", "six of these", "of these involve", "these involve activation:", "involve activation: phosphorylation", "activation: phosphorylation of", "phosphorylation of hsl", "hsl dimerization", "dimerization of hsl", "hsl disruption", "disruption of cgi", "of cgi 58:perilipin", "cgi 58:perilipin complexes", "58:perilipin complexes at", "complexes at the", "surfaces of cytosolic", "of cytosolic lipid", "cytosolic lipid particles", "particles phosphorylation", "phosphorylation of perilipin", "perilipin association", "association of phosphorylated", "of phosphorylated hsl", "phosphorylated hsl with", "hsl with fabp", "fabp and", "and translocation of", "translocation of hsl", "of hsl from", "hsl from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the surfaces", "surfaces of lipid", "of lipid particles.", "lipid particles. the", "particles. the next", "the next four", "next four reactions", "four reactions are", "reactions are the", "are the hydrolysis", "the hydrolysis reactions", "hydrolysis reactions themselves:", "reactions themselves: the", "themselves: the hydrolysis", "the hydrolysis of", "hydrolysis of cholesterol", "of cholesterol esters", "esters and", "and the successive", "the successive removal", "successive removal of", "removal of three", "of three fatty", "three fatty acids", "fatty acids from", "acids from triacylglycerol.", "from triacylglycerol. the", "triacylglycerol. the last", "the last two", "last two reactions", "reactions dephosphorylation", "dephosphorylation of perilipin", "of perilipin and", "perilipin and hsl", "hsl negatively", "negatively regulate the", "regulate the pathway.", "the pathway. these", "pathway. these events", "these events are", "events are outlined", "are outlined in", "outlined in the", "in the figure", "the figure below.", "figure below. inputs", "inputs substrates", "substrates and", "outputs products", "products of", "of individual reactions", "individual reactions are", "reactions are connected", "are connected by", "connected by black", "by black arrows", "arrows blue", "blue lines connect", "lines connect output", "connect output activated", "output activated enzymes", "activated enzymes to", "to the other", "the other reactions", "other reactions that", "reactions that they", "that they catalyze.", "they catalyze.

despite", "catalyze.

despite the", "

despite the undoubted", "the undoubted importance", "undoubted importance of", "importance of these", "of these reactions", "these reactions in", "reactions in normal", "in normal human", "normal human energy", "human energy metabolism", "energy metabolism and", "metabolism and in", "and in the", "in the pathology", "the pathology of", "pathology of diseases", "of diseases such", "diseases such as", "such as type", "as type ii", "type ii diabetes", "diabetes they", "they have been", "have been studied", "been studied only", "studied only to", "only to a", "to a limited", "a limited extent", "limited extent in", "extent in human", "in human cells", "human cells and", "cells and tissues.", "and tissues. most", "tissues. most experimental", "most experimental data", "experimental data are", "data are derived", "are derived instead", "derived instead from", "instead from two", "from two rodent", "two rodent model", "rodent model systems:", "model systems: primary", "systems: primary adipocytes", "primary adipocytes from", "adipocytes from rats", "rats and", "and mouse 3t3", "mouse 3t3 l1", "3t3 l1 cells", "l1 cells induced", "cells induced to", "induced to differentiate", "to differentiate into", "differentiate into adipocytes.", "triacylglycerol is a major", "is a major energy", "a major energy store", "major energy store in", "energy store in the", "store in the body", "in the body and", "the body and its", "body and its hydrolysis", "and its hydrolysis to", "its hydrolysis to yield", "hydrolysis to yield fatty", "to yield fatty acids", "yield fatty acids and", "fatty acids and glycerol", "acids and glycerol is", "and glycerol is a", "glycerol is a tightly", "is a tightly regulated", "a tightly regulated part", "tightly regulated part of", "regulated part of energy", "part of energy metabolism.", "of energy metabolism. a", "energy metabolism. a central", "metabolism. a central part", "a central part in", "central part in this", "part in this regulation", "in this regulation is", "this regulation is played", "regulation is played by", "is played by hormone", "played by hormone sensitive", "by hormone sensitive lipase", "sensitive lipase hsl", "hsl a", "a neutral lipase abundant", "neutral lipase abundant in", "lipase abundant in adipocytes", "abundant in adipocytes and", "in adipocytes and skeletal", "adipocytes and skeletal and", "and skeletal and cardiac", "skeletal and cardiac muscle", "cardiac muscle but", "muscle but also", "but also abundant in", "also abundant in ovarian", "abundant in ovarian and", "in ovarian and adrenal", "ovarian and adrenal tissue", "adrenal tissue where", "tissue where it", "where it mediates cholesterol", "it mediates cholesterol ester", "mediates cholesterol ester hydrolysis", "ester hydrolysis yielding", "hydrolysis yielding cholesterol", "yielding cholesterol for steroid", "cholesterol for steroid biosynthesis.", "for steroid biosynthesis. the", "steroid biosynthesis. the hormones", "biosynthesis. the hormones to", "the hormones to which", "hormones to which it", "to which it is", "which it is sensitive", "it is sensitive include", "is sensitive include catecholamines", "include catecholamines e.g.", "epinephrine acth", "acth and glucagon", "and glucagon all", "glucagon all of", "all of which trigger", "of which trigger signaling", "which trigger signaling cascades", "trigger signaling cascades that", "signaling cascades that lead", "cascades that lead to", "that lead to its", "lead to its phosphorylation", "to its phosphorylation and", "its phosphorylation and activation", "and activation and", "activation and insulin", "and insulin which", "insulin which sets", "which sets off events", "sets off events leading", "off events leading to", "events leading to its", "leading to its dephosphorylation", "to its dephosphorylation and", "its dephosphorylation and inactivation", "and inactivation holm", "inactivation holm et", "holm et al. 2000", "al. 2000 kraemer", "2000 kraemer and", "kraemer and shen 2002", "and shen 2002 .

the", "shen 2002 .

the processes", "2002 .

the processes of", ".

the processes of triacylglycerol", "processes of triacylglycerol and", "of triacylglycerol and cholesterol", "triacylglycerol and cholesterol ester", "and cholesterol ester hydrolysis", "cholesterol ester hydrolysis are", "ester hydrolysis are also", "hydrolysis are also regulated", "are also regulated by", "also regulated by subcellular", "regulated by subcellular compartmentalization:", "by subcellular compartmentalization: these", "subcellular compartmentalization: these lipids", "compartmentalization: these lipids are", "these lipids are packaged", "lipids are packaged in", "are packaged in cytosolic", "packaged in cytosolic particles", "in cytosolic particles and", "cytosolic particles and the", "particles and the enzymes", "and the enzymes responsible", "the enzymes responsible for", "enzymes responsible for their", "responsible for their hydrolysis", "their hydrolysis and", "hydrolysis and perhaps", "and perhaps for additional", "perhaps for additional steps", "for additional steps in", "additional steps in their", "steps in their metabolism", "their metabolism are", "metabolism are organized", "are organized at the", "organized at the surfaces", "at the surfaces of", "the surfaces of these", "surfaces of these particles", "these particles e.g.", "e.g. brasaemle et", "brasaemle et al. 2004", "et al. 2004 .", "al. 2004 . this", "2004 . this organization", ". this organization is", "this organization is dynamic:", "organization is dynamic: the", "is dynamic: the inactive", "dynamic: the inactive form", "the inactive form of", "inactive form of hsl", "form of hsl is", "of hsl is not", "hsl is not associated", "is not associated with", "not associated with the", "associated with the particles", "the particles but", "particles but is", "but is translocated there", "is translocated there after", "translocated there after being", "there after being phosphorylated.", "after being phosphorylated. conversely", "phosphorylated. conversely perilipin", "perilipin a major", "a major constituent of", "major constituent of the", "constituent of the particle", "of the particle surface", "particle surface appears", "surface appears to", "appears to block access", "to block access of", "block access of enzymes", "access of enzymes to", "of enzymes to the", "enzymes to the lipids", "to the lipids within", "the lipids within the", "lipids within the particle", "the particle its", "particle its phosphorylation", "its phosphorylation allows greater", "phosphorylation allows greater access.", "allows greater access.

here", "access.

here hsl", "

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despite", "they catalyze.

despite the", "catalyze.

despite the undoubted", "

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the", "and shen 2002 .

the processes", "shen 2002 .

the processes of", "2002 .

the processes of triacylglycerol", ".

the processes of triacylglycerol and", "processes of triacylglycerol and cholesterol", "of triacylglycerol and cholesterol ester", "triacylglycerol and cholesterol ester hydrolysis", "and cholesterol ester hydrolysis are", "cholesterol ester hydrolysis are also", "ester hydrolysis are also regulated", "hydrolysis are also regulated by", "are also regulated by subcellular", "also regulated by subcellular compartmentalization:", "regulated by subcellular compartmentalization: these", "by subcellular compartmentalization: these lipids", "subcellular compartmentalization: these lipids are", "compartmentalization: these lipids are packaged", "these lipids are packaged in", "lipids are packaged in cytosolic", "are packaged in cytosolic particles", "packaged in cytosolic particles and", "in cytosolic particles and the", "cytosolic particles and the enzymes", "particles and the enzymes responsible", "and the enzymes responsible for", "the enzymes responsible for their", "enzymes responsible for their hydrolysis", "for their hydrolysis and", "their hydrolysis and perhaps", "hydrolysis and perhaps for", "and perhaps for additional steps", "perhaps for additional steps in", "for additional steps in their", "additional steps in their metabolism", "in their metabolism are", "their metabolism are organized", "metabolism are organized at", "are organized at the surfaces", "organized at the surfaces of", "at the surfaces of these", "the surfaces of these particles", "of these particles e.g.", "particles e.g. brasaemle", "e.g. brasaemle et al.", "brasaemle et al. 2004 .", "et al. 2004 . this", "al. 2004 . this organization", "2004 . this organization is", ". this organization is dynamic:", "this organization is dynamic: the", "organization is dynamic: the inactive", "is dynamic: the inactive form", "dynamic: the inactive form of", "the inactive form of hsl", "inactive form of hsl is", "form of hsl is not", "of hsl is not associated", "hsl is not associated with", "is not associated with the", "not associated with the particles", "with the particles but", "the particles but is", "particles but is translocated", "but is translocated there after", "is translocated there after being", "translocated there after being phosphorylated.", "there after being phosphorylated. conversely", "being phosphorylated. conversely perilipin", "conversely perilipin a", "perilipin a major constituent", "a major constituent of the", "major constituent of the particle", "constituent of the particle surface", "the particle surface appears", "particle surface appears to", "surface appears to block", "appears to block access of", "to block access of enzymes", "block access of enzymes to", "access of enzymes to the", "of enzymes to the lipids", "enzymes to the lipids within", "to the lipids within the", "the lipids within the particle", "within the particle its", "the particle its phosphorylation", "particle its phosphorylation allows", "its phosphorylation allows greater access.", "phosphorylation allows greater access.

here", "greater access.

here hsl", "access.

here hsl mediated", "

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despite", "that they catalyze.

despite the", "they catalyze.

despite the undoubted", "catalyze.

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lumen.", "lumen. propeptides", "propeptides undergo", "undergo a", "a number", "number of", "of post", "post translational", "translational modifications.", "modifications. proline", "proline and", "and lysine", "lysine residues", "residues may", "may be", "be hydroxylated", "hydroxylated by", "by prolyl", "prolyl 3", "prolyl 4", "and lysyl", "lysyl hydroxylases.", "hydroxylases. 4", "4 hydroxyproline", "hydroxyproline is", "is essential", "essential for", "for intramolecular", "intramolecular hydrogen", "hydrogen bonding", "bonding and", "and stability", "stability of", "of the", "the triple", "triple helical", "helical collagenous", "collagenous domain.", "domain. in", "in fibril", "fibril forming", "forming collagens", "collagens approximately", "approximately 50%", "50% of", "of prolines", "prolines are", "are 4", "4 hydroxylated", "the extent", "extent of", "of this", "this and", "and of", "of 3", "3 hydroxyproline", "hydroxyproline and", "lysine hydroxylation", "hydroxylation varies", "varies between", "between tissues", "tissues and", "and collagen", "collagen types", "kivirikko et", "et al.", "al. 1972", "1992 .", ". hydroxylysine", "hydroxylysine molecules", "molecules can", "can form", "form cross", "cross links", "links between", "between collagen", "collagen molecules", "molecules in", "in fibrils", "and are", "are sites", "sites for", "for glycosyl", "and galactosylation.", "galactosylation. collagen", "collagen peptides", "peptides all", "all have", "have non", "non collagenous", "collagenous domains", "collagens within", "within the", "the subclasses", "subclasses have", "have common", "common chain", "chain structures.", "structures. these", "these non", "domains have", "have regulatory", "regulatory functions", "some are", "are biologically", "biologically active", "active when", "when cleaved", "cleaved from", "from the", "the main", "main peptide", "peptide chain.", "chain. fibrillar", "fibrillar collagens", "collagens all", "have a", "a large", "large triple", "helical domain", "bordered by", "by n", "n and", "and c", "c terminal", "terminal extensions", "called the", "the n", "c propeptides", "which are", "are cleaved", "cleaved prior", "prior to", "to formation", "formation of", "the collagen", "collagen fibril.", "fibril. the", "the c", "c propeptide", "also called", "the nc1", "nc1 domain", "is highly", "highly conserved.", "conserved. it", "it directs", "directs chain", "chain association", "association during", "during intracellular", "intracellular assembly", "assembly of", "the procollagen", "procollagen molecule", "molecule from", "from three", "three collagen", "collagen propeptide", "propeptide alpha", "alpha chains", "hulmes 2002", "2002 .", ". the", "n propeptide", "propeptide has", "has a", "a short", "short linker", "connecting the", "main triple", "triple helix", "helix to", "to a", "short minor", "minor one", "and a", "a globular", "globular n", "n terminal", "terminal region", "region nc3.", "nc3. nc3", "nc3 domains", "domains are", "are variable", "variable both", "both in", "in size", "size and", "and the", "the domains", "domains they", "they contain.

collagen", "contain.

collagen propeptides", "propeptides typically", "typically undergo", "residues are", "are hydroxylated", "domain. prolyl", "4 hydroxylase", "hydroxylase may", "may also", "also have", "a role", "role in", "in alpha", "alpha chain", "association as", "as no", "no association", "association of", "propeptides of", "of type", "type xii", "xii collagen", "collagen was", "was seen", "seen in", "in the", "the presence", "presence of", "of prolyl", "hydroxylase inhibitors", "mazzorana et", "al. 1993", "1996 .", ". in", "this is", "is species", "species dependent", "lower hydroxylation", "hydroxylation correlating", "correlating with", "with lower", "lower ambient", "ambient temperature", "temperature and", "and thermal", "thermal stability", "cohen solal", "solal et", "al. 1986", "notbohm et", "al. 1992", ". similarly", "similarly the", "and galactosylation.

collagen", "galactosylation.

collagen molecules", "molecules fold", "fold and", "and assemble", "assemble through", "through a", "a series", "series of", "of distinct", "distinct intermediates", "bulleid 1996", ". individual", "individual collagen", "collagen polypeptide", "polypeptide chains", "chains are", "are translocated", "translocated co", "co translationally", "translationally across", "across the", "the membrane", "membrane of", "the endoplasmic", "endoplasmic reticulum", "er .", ". intra", "intra chain", "chain disulfide", "disulfide bonds", "bonds are", "are formed", "formed within", "and hydroxylation", "hydroxylation of", "of proline", "residues occurs", "occurs within", ". when", "when the", "the peptide", "peptide chain", "chain is", "is fully", "fully translocated", "er lumen", "lumen the", "propeptide folds", "the conformation", "conformation being", "being stabilized", "stabilized by", "by intra", "doege and", "and fessler", "fessler 1986", "1986 .", ". pro", "pro alpha", "chains associate", "associate via", "via the", "byers et", "al. 1975", "bachinger et", "al. 1978", "or nc2", "nc2 domains", "domains for", "for facit", "facit family", "family collagens", "boudko et", "al. 2008", "to form", "form an", "an initial", "initial trimer", "trimer which", "which can", "can be", "be stabilized", "by the", "the formation", "of inter", "inter chain", "schofield et", "al. 1974", "olsen et", "al. 1976", "though these", "these are", "are not", "not a", "a prerequisite", "prerequisite for", "for further", "further folding", "bulleid et", "al. 1996", "helix then", "then nucleates", "nucleates and", "and folds", "folds in", "in a", "a c", "to n", "direction. the", "the association", "the individual", "individual chains", "chains and", "and subsequent", "subsequent triple", "helix formation", "formation are", "are distinct", "distinct steps", "al. 1980", "1980 .", "n propeptides", "propeptides associate", "associate and", "and in", "in some", "some cases", "cases form", "form inter", "bruckner et", "1978 .", ". procollagen", "procollagen is", "is released", "released via", "via carriers", "carriers into", "the exracellular", "exracellular space", "canty &", "& kadler", "kadler 2005", "2005 .", ". fibrillar", "fibrillar procollagens", "procollagens undergo", "undergo removal", "removal of", "and n", "propeptides by", "by procollagen", "procollagen c", "c and", "n proteinases", "proteinases respectively", "both zn2+", "zn2+ dependent", "dependent metalloproteinases.", "metalloproteinases. propeptide", "propeptide processing", "processing is", "a required", "required step", "step for", "for normal", "normal collagen", "collagen i", "i and", "and iii", "iii fibril", "fibril formation", "but collagens", "collagens can", "can retain", "retain some", "some or", "or all", "all of", "of their", "their non", "collagenous propeptides.", "propeptides. retained", "retained collagen", "collagen type", "type v", "v and", "and xi", "xi n", "propeptides contribute", "contribute to", "to the", "the control", "control of", "of fibril", "fibril growth", "growth by", "by sterically", "sterically limiting", "limiting lateral", "lateral molecule", "molecule addition", "fichard et", "al. 1995", "1995 .", ". processed", "processed fibrillar", "fibrillar procollagen", "is termed", "termed tropocollagen", "which is", "is considered", "considered to", "to be", "be the", "the unit", "unit of", "of higher", "higher order", "order fibrils", "fibrils and", "and fibres.", "fibres. tropocollagens", "tropocollagens of", "the fibril", "collagens i", "xi sponteneously", "sponteneously aggregate", "aggregate in", "in vitro", "vitro in", "a manner", "manner that", "that has", "has been", "been compared", "compared with", "with crystallization", "commencing with", "with a", "a nucleation", "nucleation event", "event followed", "followed by", "by subsequent", "subsequent organized", "organized aggregation", "silver et", "prockop &", "& fertala", "fertala 1998", "1998 .", ". fibril", "formation is", "is stabilized", "by lysyl", "lysyl oxidase", "oxidase catalyzed", "catalyzed crosslinks", "crosslinks between", "between adjacent", "adjacent molecules", "siegel &", "fu 1976", "1976 .", "the biosynthesis of", "biosynthesis of collagen", "of collagen is", "collagen is a", "is a multistep", "a multistep process.", "multistep process. collagen", "process. collagen propeptides", "collagen propeptides are", "propeptides are cotranslationally", "are cotranslationally translocated", "cotranslationally translocated into", "translocated into the", "into the er", "the er lumen.", "er lumen. propeptides", "lumen. propeptides undergo", "propeptides undergo a", "undergo a number", "a number of", "number of post", "of post translational", "post translational modifications.", "translational modifications. proline", "modifications. proline and", "proline and lysine", "and lysine residues", "lysine residues may", "residues may be", "may be hydroxylated", "be hydroxylated by", "hydroxylated by prolyl", "by prolyl 3", "4 and", "and lysyl hydroxylases.", "lysyl hydroxylases. 4", "hydroxylases. 4 hydroxyproline", "4 hydroxyproline is", "hydroxyproline is essential", "is essential for", "essential for intramolecular", "for intramolecular hydrogen", "intramolecular hydrogen bonding", "hydrogen bonding and", "bonding and stability", "and stability of", "stability of the", "of the triple", "the triple helical", "triple helical collagenous", "helical collagenous domain.", "collagenous domain. in", "domain. in fibril", "in fibril forming", "fibril forming collagens", "forming collagens approximately", "collagens approximately 50%", "approximately 50% of", "50% of prolines", "of prolines are", "prolines are 4", "are 4 hydroxylated", "hydroxylated the", "the extent of", "extent of this", "of this and", "this and of", "and of 3", "of 3 hydroxyproline", "3 hydroxyproline and", "hydroxyproline and lysine", "and lysine hydroxylation", "lysine hydroxylation varies", "hydroxylation varies between", "varies between tissues", "between tissues and", "tissues and collagen", "and collagen types", "types kivirikko", "kivirikko et al.", "et al. 1972", "1972 1992", "1992 . hydroxylysine", ". hydroxylysine molecules", "hydroxylysine molecules can", "molecules can form", "can form cross", "form cross links", "cross links between", "links between collagen", "between collagen molecules", "collagen molecules in", "molecules in fibrils", "and are sites", "are sites for", "sites for glycosyl", "glycosyl and", "and galactosylation. collagen", "galactosylation. collagen peptides", "collagen peptides all", "peptides all have", "all have non", "have non collagenous", "non collagenous domains", "domains collagens", "collagens within the", "within the subclasses", "the subclasses have", "subclasses have common", "have common chain", "common chain structures.", "chain structures. these", "structures. these non", "these non collagenous", "collagenous domains have", "domains have regulatory", "have regulatory functions", "functions some", "some are biologically", "are biologically active", "biologically active when", "active when cleaved", "when cleaved from", "cleaved from the", "from the main", "the main peptide", "main peptide chain.", "peptide chain. fibrillar", "chain. fibrillar collagens", "fibrillar collagens all", "collagens all have", "all have a", "have a large", "a large triple", "large triple helical", "triple helical domain", "domain col1", "col1 bordered", "bordered by n", "by n and", "n and c", "and c terminal", "c terminal extensions", "extensions called", "called the n", "the n and", "and c propeptides", "propeptides which", "which are cleaved", "are cleaved prior", "cleaved prior to", "prior to formation", "to formation of", "formation of the", "of the collagen", "the collagen fibril.", "collagen fibril. the", "fibril. the c", "the c propeptide", "propeptide also", "also called the", "called the nc1", "the nc1 domain", "domain is", "is highly conserved.", "highly conserved. it", "conserved. it directs", "it directs chain", "directs chain association", "chain association during", "association during intracellular", "during intracellular assembly", "intracellular assembly of", "assembly of the", "of the procollagen", "the procollagen molecule", "procollagen molecule from", "molecule from three", "from three collagen", "three collagen propeptide", "collagen propeptide alpha", "propeptide alpha chains", "chains hulmes", "hulmes 2002 .", "2002 . the", ". the n", "the n propeptide", "n propeptide has", "propeptide has a", "has a short", "a short linker", "linker nc2", "nc2 connecting", "connecting the main", "the main triple", "main triple helix", "triple helix to", "helix to a", "to a short", "a short minor", "short minor one", "one col2", "col2 and", "and a globular", "a globular n", "globular n terminal", "n terminal region", "terminal region nc3.", "region nc3. nc3", "nc3. nc3 domains", "nc3 domains are", "domains are variable", "are variable both", "variable both in", "both in size", "in size and", "size and the", "and the domains", "the domains they", "domains they contain.

collagen", "they contain.

collagen propeptides", "contain.

collagen propeptides typically", "propeptides typically undergo", "typically undergo a", "lysine residues are", "residues are hydroxylated", "are hydroxylated by", "collagenous domain. prolyl", "domain. prolyl 4", "prolyl 4 hydroxylase", "4 hydroxylase may", "hydroxylase may also", "may also have", "also have a", "have a role", "a role in", "role in alpha", "in alpha chain", "alpha chain association", "chain association as", "association as no", "as no association", "no association of", "association of the", "of the c", "the c propeptides", "c propeptides of", "propeptides of type", "of type xii", "type xii collagen", "xii collagen was", "collagen was seen", "was seen in", "seen in the", "in the presence", "the presence of", "presence of prolyl", "of prolyl 4", "4 hydroxylase inhibitors", "inhibitors mazzorana", "mazzorana et al.", "et al. 1993", "1993 1996", "1996 . in", ". in fibril", "of this is", "this is species", "is species dependent", "dependent lower", "lower hydroxylation correlating", "hydroxylation correlating with", "correlating with lower", "with lower ambient", "lower ambient temperature", "ambient temperature and", "temperature and thermal", "and thermal stability", "stability cohen", "cohen solal et", "solal et al.", "et al. 1986", "1986 notbohm", "notbohm et al.", "et al. 1992", "al. 1992 .", "1992 . similarly", ". similarly the", "similarly the extent", "extent of 3", "and galactosylation.

collagen molecules", "galactosylation.

collagen molecules fold", "molecules fold and", "fold and assemble", "and assemble through", "assemble through a", "through a series", "a series of", "series of distinct", "of distinct intermediates", "intermediates bulleid", "bulleid 1996 .", "1996 . individual", ". individual collagen", "individual collagen polypeptide", "collagen polypeptide chains", "polypeptide chains are", "chains are translocated", "are translocated co", "translocated co translationally", "co translationally across", "translationally across the", "across the membrane", "the membrane of", "membrane of the", "of the endoplasmic", "the endoplasmic reticulum", "reticulum er", "er . intra", ". intra chain", "intra chain disulfide", "chain disulfide bonds", "disulfide bonds are", "bonds are formed", "are formed within", "formed within the", "within the n", "propeptide and", "and hydroxylation of", "hydroxylation of proline", "of proline and", "lysine residues occurs", "residues occurs within", "occurs within the", "within the triple", "domain kivirikko", "1992 . when", ". when the", "when the peptide", "the peptide chain", "peptide chain is", "chain is fully", "is fully translocated", "fully translocated into", "the er lumen", "er lumen the", "lumen the c", "c propeptide folds", "folds the", "the conformation being", "conformation being stabilized", "being stabilized by", "stabilized by intra", "by intra chain", "bonds doege", "doege and fessler", "and fessler 1986", "fessler 1986 .", "1986 . pro", ". pro alpha", "pro alpha chains", "alpha chains associate", "chains associate via", "associate via the", "via the c", "propeptides byers", "byers et al.", "et al. 1975", "1975 bachinger", "bachinger et al.", "et al. 1978", "or nc2 domains", "nc2 domains for", "domains for facit", "for facit family", "facit family collagens", "collagens boudko", "boudko et al.", "et al. 2008", "2008 to", "to form an", "form an initial", "an initial trimer", "initial trimer which", "trimer which can", "which can be", "can be stabilized", "be stabilized by", "stabilized by the", "by the formation", "the formation of", "formation of inter", "of inter chain", "inter chain disulfide", "bonds schofield", "schofield et al.", "et al. 1974", "1974 olsen", "olsen et al.", "et al. 1976", "though these are", "these are not", "are not a", "not a prerequisite", "a prerequisite for", "prerequisite for further", "for further folding", "folding bulleid", "bulleid et al.", "et al. 1996", "al. 1996 .", "1996 . the", ". the triple", "the triple helix", "triple helix then", "helix then nucleates", "then nucleates and", "nucleates and folds", "and folds in", "folds in a", "in a c", "c to", "n direction.", "direction. the association", "the association of", "of the individual", "the individual chains", "individual chains and", "chains and subsequent", "and subsequent triple", "subsequent triple helix", "triple helix formation", "helix formation are", "formation are distinct", "are distinct steps", "steps bachinger", "et al. 1980", "al. 1980 .", "1980 . the", "the n propeptides", "n propeptides associate", "propeptides associate and", "associate and in", "and in some", "in some cases", "some cases form", "cases form inter", "form inter chain", "bonds bruckner", "bruckner et al.", "1978 . procollagen", ". procollagen is", "procollagen is released", "is released via", "released via carriers", "via carriers into", "carriers into the", "into the exracellular", "the exracellular space", "space canty", "canty & kadler", "& kadler 2005", "kadler 2005 .", "2005 . fibrillar", ". fibrillar procollagens", "fibrillar procollagens undergo", "procollagens undergo removal", "undergo removal of", "removal of the", "and n propeptides", "n propeptides by", "propeptides by procollagen", "by procollagen c", "procollagen c and", "c and n", "and n proteinases", "n proteinases respectively", "respectively both", "both zn2+ dependent", "zn2+ dependent metalloproteinases.", "dependent metalloproteinases. propeptide", "metalloproteinases. propeptide processing", "propeptide processing is", "processing is a", "is a required", "a required step", "required step for", "step for normal", "for normal collagen", "normal collagen i", "collagen i and", "i and iii", "and iii fibril", "iii fibril formation", "formation but", "but collagens can", "collagens can retain", "can retain some", "retain some or", "some or all", "or all of", "all of their", "of their non", "their non collagenous", "non collagenous propeptides.", "collagenous propeptides. retained", "propeptides. retained collagen", "retained collagen type", "collagen type v", "type v and", "v and xi", "and xi n", "xi n propeptides", "n propeptides contribute", "propeptides contribute to", "contribute to the", "to the control", "the control of", "control of fibril", "of fibril growth", "fibril growth by", "growth by sterically", "by sterically limiting", "sterically limiting lateral", "limiting lateral molecule", "lateral molecule addition", "addition fichard", "fichard et al.", "et al. 1995", "al. 1995 .", "1995 . processed", ". processed fibrillar", "processed fibrillar procollagen", "fibrillar procollagen is", "procollagen is termed", "is termed tropocollagen", "tropocollagen which", "which is considered", "is considered to", "considered to be", "to be the", "be the unit", "the unit of", "unit of higher", "of higher order", "higher order fibrils", "order fibrils and", "fibrils and fibres.", "and fibres. tropocollagens", "fibres. tropocollagens of", "tropocollagens of the", "of the fibril", "the fibril forming", "forming collagens i", "i ii", "ii iii", "iii v", "and xi sponteneously", "xi sponteneously aggregate", "sponteneously aggregate in", "aggregate in vitro", "in vitro in", "vitro in a", "in a manner", "a manner that", "manner that has", "that has been", "has been compared", "been compared with", "compared with crystallization", "crystallization commencing", "commencing with a", "with a nucleation", "a nucleation event", "nucleation event followed", "event followed by", "followed by subsequent", "by subsequent organized", "subsequent organized aggregation", "aggregation silver", "silver et al.", "1992 prockop", "prockop & fertala", "& fertala 1998", "fertala 1998 .", "1998 . fibril", ". fibril formation", "fibril formation is", "formation is stabilized", "is stabilized by", "stabilized by lysyl", "by lysyl oxidase", "lysyl oxidase catalyzed", "oxidase catalyzed crosslinks", "catalyzed crosslinks between", "crosslinks between adjacent", "between adjacent molecules", "molecules siegel", "& fu", "fu 1976 .", "the biosynthesis of collagen", "biosynthesis of collagen is", "of collagen is a", "collagen is a multistep", "is a multistep process.", "a multistep process. collagen", "multistep process. collagen propeptides", "process. collagen propeptides are", "collagen propeptides are cotranslationally", "propeptides are cotranslationally translocated", "are cotranslationally translocated into", "cotranslationally translocated into the", "translocated into the er", "into the er lumen.", "the er lumen. propeptides", "er lumen. propeptides undergo", "lumen. propeptides undergo a", "propeptides undergo a number", "undergo a number of", "a number of post", "number of post translational", "of post translational modifications.", "post translational modifications. proline", "translational modifications. proline and", "modifications. proline and lysine", "proline and lysine residues", "and lysine residues may", "lysine residues may be", "residues may be hydroxylated", "may be hydroxylated by", "be hydroxylated by prolyl", "hydroxylated by prolyl 3", "3 prolyl", "prolyl 4 and", "4 and lysyl", "and lysyl hydroxylases. 4", "lysyl hydroxylases. 4 hydroxyproline", "hydroxylases. 4 hydroxyproline is", "4 hydroxyproline is essential", "hydroxyproline is essential for", "is essential for intramolecular", "essential for intramolecular hydrogen", "for intramolecular hydrogen bonding", "intramolecular hydrogen bonding and", "hydrogen bonding and stability", "bonding and stability of", "and stability of the", "stability of the triple", "of the triple helical", "the triple helical collagenous", "triple helical collagenous domain.", "helical collagenous domain. in", "collagenous domain. in fibril", "domain. in fibril forming", "in fibril forming collagens", "fibril forming collagens approximately", "forming collagens approximately 50%", "collagens approximately 50% of", "approximately 50% of prolines", "50% of prolines are", "of prolines are 4", "prolines are 4 hydroxylated", "4 hydroxylated the", "hydroxylated the extent", "the extent of this", "extent of this and", "of this and of", "this and of 3", "and of 3 hydroxyproline", "of 3 hydroxyproline and", "3 hydroxyproline and lysine", "hydroxyproline and lysine hydroxylation", "and lysine hydroxylation varies", "lysine hydroxylation varies between", "hydroxylation varies between tissues", "varies between tissues and", "between tissues and collagen", "tissues and collagen types", "collagen types kivirikko", "types kivirikko et", "kivirikko et al. 1972", "al. 1972 1992", "1972 1992 .", "1992 . hydroxylysine molecules", ". hydroxylysine molecules can", "hydroxylysine molecules can form", "molecules can form cross", "can form cross links", "form cross links between", "cross links between collagen", "links between collagen molecules", "between collagen molecules in", "collagen molecules in fibrils", "in fibrils and", "fibrils and are", "and are sites for", "are sites for glycosyl", "for glycosyl and", "glycosyl and galactosylation.", "and galactosylation. collagen peptides", "galactosylation. collagen peptides all", "collagen peptides all have", "peptides all have non", "all have non collagenous", "have non collagenous domains", "collagenous domains collagens", "domains collagens within", "collagens within the subclasses", "within the subclasses have", "the subclasses have common", "subclasses have common chain", "have common chain structures.", "common chain structures. these", "chain structures. these non", "structures. these non collagenous", "these non collagenous domains", "non collagenous domains have", "collagenous domains have regulatory", "domains have regulatory functions", "regulatory functions some", "functions some are", "some are biologically active", "are biologically active when", "biologically active when cleaved", "active when cleaved from", "when cleaved from the", "cleaved from the main", "from the main peptide", "the main peptide chain.", "main peptide chain. fibrillar", "peptide chain. fibrillar collagens", "chain. fibrillar collagens all", "fibrillar collagens all have", "collagens all have a", "all have a large", "have a large triple", "a large triple helical", "large triple helical domain", "helical domain col1", "col1 bordered by", "bordered by n and", "by n and c", "n and c terminal", "and c terminal extensions", "terminal extensions called", "extensions called the", "called the n and", "the n and c", "n and c propeptides", "c propeptides which", "propeptides which are", "which are cleaved prior", "are cleaved prior to", "cleaved prior to formation", "prior to formation of", "to formation of the", "formation of the collagen", "of the collagen fibril.", "the collagen fibril. the", "collagen fibril. the c", "fibril. the c propeptide", "c propeptide also", "propeptide also called", "also called the nc1", "called the nc1 domain", "nc1 domain is", "domain is highly", "is highly conserved. it", "highly conserved. it directs", "conserved. it directs chain", "it directs chain association", "directs chain association during", "chain association during intracellular", "association during intracellular assembly", "during intracellular assembly of", "intracellular assembly of the", "assembly of the procollagen", "of the procollagen molecule", "the procollagen molecule from", "procollagen molecule from three", "molecule from three collagen", "from three collagen propeptide", "three collagen propeptide alpha", "collagen propeptide alpha chains", "alpha chains hulmes", "chains hulmes 2002", "hulmes 2002 . the", "2002 . the n", ". the n propeptide", "the n propeptide has", "n propeptide has a", "propeptide has a short", "has a short linker", "short linker nc2", "nc2 connecting the", "connecting the main triple", "the main triple helix", "main triple helix to", "triple helix to a", "helix to a short", "to a short minor", "a short minor one", "minor one col2", "col2 and a", "and a globular n", "a globular n terminal", "globular n terminal region", "n terminal region nc3.", "terminal region nc3. nc3", "region nc3. nc3 domains", "nc3. nc3 domains are", "nc3 domains are variable", "domains are variable both", "are variable both in", "variable both in size", "both in size and", "in size and the", "size and the domains", "and the domains they", "the domains they contain.

collagen", "domains they contain.

collagen propeptides", "they contain.

collagen propeptides typically", "contain.

collagen propeptides typically undergo", "propeptides typically undergo a", "typically undergo a number", "and lysine residues are", "lysine residues are hydroxylated", "residues are hydroxylated by", "are hydroxylated by prolyl", "helical collagenous domain. prolyl", "collagenous domain. prolyl 4", "domain. prolyl 4 hydroxylase", "prolyl 4 hydroxylase may", "4 hydroxylase may also", "hydroxylase may also have", "may also have a", "also have a role", "have a role in", "a role in alpha", "role in alpha chain", "in alpha chain association", "alpha chain association as", "chain association as no", "association as no association", "as no association of", "no association of the", "association of the c", "of the c propeptides", "the c propeptides of", "c propeptides of type", "propeptides of type xii", "of type xii collagen", "type xii collagen was", "xii collagen was seen", "collagen was seen in", "was seen in the", "seen in the presence", "in the presence of", "the presence of prolyl", "presence of prolyl 4", "of prolyl 4 hydroxylase", "prolyl 4 hydroxylase inhibitors", "hydroxylase inhibitors mazzorana", "inhibitors mazzorana et", "mazzorana et al. 1993", "al. 1993 1996", "1993 1996 .", "1996 . in fibril", ". in fibril forming", "extent of this is", "of this is species", "this is species dependent", "species dependent lower", "dependent lower hydroxylation", "lower hydroxylation correlating with", "hydroxylation correlating with lower", "correlating with lower ambient", "with lower ambient temperature", "lower ambient temperature and", "ambient temperature and thermal", "temperature and thermal stability", "thermal stability cohen", "stability cohen solal", "cohen solal et al.", "solal et al. 1986", "al. 1986 notbohm", "1986 notbohm et", "notbohm et al. 1992", "et al. 1992 .", "al. 1992 . similarly", "1992 . similarly the", ". similarly the extent", "similarly the extent of", "the extent of 3", "extent of 3 hydroxyproline", "kivirikko et al. 1992", "al. 1992 . hydroxylysine", "glycosyl and galactosylation.

collagen", "and galactosylation.

collagen molecules fold", "galactosylation.

collagen molecules fold and", "molecules fold and assemble", "fold and assemble through", "and assemble through a", "assemble through a series", "through a series of", "a series of distinct", "series of distinct intermediates", "distinct intermediates bulleid", "intermediates bulleid 1996", "bulleid 1996 . individual", "1996 . individual collagen", ". individual collagen polypeptide", "individual collagen polypeptide chains", "collagen polypeptide chains are", "polypeptide chains are translocated", "chains are translocated co", "are translocated co translationally", "translocated co translationally across", "co translationally across the", "translationally across the membrane", "across the membrane of", "the membrane of the", "membrane of the endoplasmic", "of the endoplasmic reticulum", "endoplasmic reticulum er", "reticulum er .", "er . intra chain", ". intra chain disulfide", "intra chain disulfide bonds", "chain disulfide bonds are", "disulfide bonds are formed", "bonds are formed within", "are formed within the", "formed within the n", "within the n propeptide", "n propeptide and", "propeptide and hydroxylation", "and hydroxylation of proline", "hydroxylation of proline and", "of proline and lysine", "and lysine residues occurs", "lysine residues occurs within", "residues occurs within the", "occurs within the triple", "within the triple helical", "the triple helical domain", "helical domain kivirikko", "domain kivirikko et", "al. 1992 . when", "1992 . when the", ". when the peptide", "when the peptide chain", "the peptide chain is", "peptide chain is fully", "chain is fully translocated", "is fully translocated into", "fully translocated into the", "into the er lumen", "the er lumen the", "er lumen the c", "lumen the c propeptide", "the c propeptide folds", "propeptide folds the", "folds the conformation", "the conformation being stabilized", "conformation being stabilized by", "being stabilized by intra", "stabilized by intra chain", "by intra chain disulfide", "disulfide bonds doege", "bonds doege and", "doege and fessler 1986", "and fessler 1986 .", "fessler 1986 . pro", "1986 . pro alpha", ". pro alpha chains", "pro alpha chains associate", "alpha chains associate via", "chains associate via the", "associate via the c", "via the c propeptides", "c propeptides byers", "propeptides byers et", "byers et al. 1975", "al. 1975 bachinger", "1975 bachinger et", "bachinger et al. 1978", "1978 or", "or nc2 domains for", "nc2 domains for facit", "domains for facit family", "for facit family collagens", "family collagens boudko", "collagens boudko et", "boudko et al. 2008", "al. 2008 to", "2008 to form", "to form an initial", "form an initial trimer", "an initial trimer which", "initial trimer which can", "trimer which can be", "which can be stabilized", "can be stabilized by", "be stabilized by the", "stabilized by the formation", "by the formation of", "the formation of inter", "formation of inter chain", "of inter chain disulfide", "inter chain disulfide bonds", "disulfide bonds schofield", "bonds schofield et", "schofield et al. 1974", "al. 1974 olsen", "1974 olsen et", "olsen et al. 1976", "1976 though", "though these are not", "these are not a", "are not a prerequisite", "not a prerequisite for", "a prerequisite for further", "prerequisite for further folding", "further folding bulleid", "folding bulleid et", "bulleid et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the triple", ". the triple helix", "the triple helix then", "triple helix then nucleates", "helix then nucleates and", "then nucleates and folds", "nucleates and folds in", "and folds in a", "folds in a c", "a c to", "c to n", "to n direction.", "n direction. the", "direction. the association of", "the association of the", "association of the individual", "of the individual chains", "the individual chains and", "individual chains and subsequent", "chains and subsequent triple", "and subsequent triple helix", "subsequent triple helix formation", "triple helix formation are", "helix formation are distinct", "formation are distinct steps", "distinct steps bachinger", "steps bachinger et", "bachinger et al. 1980", "et al. 1980 .", "al. 1980 . the", "1980 . the n", ". the n propeptides", "the n propeptides associate", "n propeptides associate and", "propeptides associate and in", "associate and in some", "and in some cases", "in some cases form", "some cases form inter", "cases form inter chain", "form inter chain disulfide", "disulfide bonds bruckner", "bonds bruckner et", "al. 1978 .", "1978 . procollagen is", ". procollagen is released", "procollagen is released via", "is released via carriers", "released via carriers into", "via carriers into the", "carriers into the exracellular", "into the exracellular space", "exracellular space canty", "space canty &", "canty & kadler 2005", "& kadler 2005 .", "kadler 2005 . fibrillar", "2005 . fibrillar procollagens", ". fibrillar procollagens undergo", "fibrillar procollagens undergo removal", "procollagens undergo removal of", "undergo removal of the", "removal of the c", "the c and", "and n propeptides by", "n propeptides by procollagen", "propeptides by procollagen c", "by procollagen c and", "procollagen c and n", "c and n proteinases", "and n proteinases respectively", "proteinases respectively both", "respectively both zn2+", "both zn2+ dependent metalloproteinases.", "zn2+ dependent metalloproteinases. propeptide", "dependent metalloproteinases. propeptide processing", "metalloproteinases. propeptide processing is", "propeptide processing is a", "processing is a required", "is a required step", "a required step for", "required step for normal", "step for normal collagen", "for normal collagen i", "normal collagen i and", "collagen i and iii", "i and iii fibril", "and iii fibril formation", "fibril formation but", "formation but collagens", "but collagens can retain", "collagens can retain some", "can retain some or", "retain some or all", "some or all of", "or all of their", "all of their non", "of their non collagenous", "their non collagenous propeptides.", "non collagenous propeptides. retained", "collagenous propeptides. retained collagen", "propeptides. retained collagen type", "retained collagen type v", "collagen type v and", "type v and xi", "v and xi n", "and xi n propeptides", "xi n propeptides contribute", "n propeptides contribute to", "propeptides contribute to the", "contribute to the control", "to the control of", "the control of fibril", "control of fibril growth", "of fibril growth by", "fibril growth by sterically", "growth by sterically limiting", "by sterically limiting lateral", "sterically limiting lateral molecule", "limiting lateral molecule addition", "molecule addition fichard", "addition fichard et", "fichard et al. 1995", "et al. 1995 .", "al. 1995 . processed", "1995 . processed fibrillar", ". processed fibrillar procollagen", "processed fibrillar procollagen is", "fibrillar procollagen is termed", "procollagen is termed tropocollagen", "termed tropocollagen which", "tropocollagen which is", "which is considered to", "is considered to be", "considered to be the", "to be the unit", "be the unit of", "the unit of higher", "unit of higher order", "of higher order fibrils", "higher order fibrils and", "order fibrils and fibres.", "fibrils and fibres. tropocollagens", "and fibres. tropocollagens of", "fibres. tropocollagens of the", "tropocollagens of the fibril", "of the fibril forming", "the fibril forming collagens", "fibril forming collagens i", "collagens i ii", "iii v and", "v and xi sponteneously", "and xi sponteneously aggregate", "xi sponteneously aggregate in", "sponteneously aggregate in vitro", "aggregate in vitro in", "in vitro in a", "vitro in a manner", "in a manner that", "a manner that has", "manner that has been", "that has been compared", "has been compared with", "been compared with crystallization", "with crystallization commencing", "crystallization commencing with", "commencing with a nucleation", "with a nucleation event", "a nucleation event followed", "nucleation event followed by", "event followed by subsequent", "followed by subsequent organized", "by subsequent organized aggregation", "organized aggregation silver", "aggregation silver et", "silver et al. 1992", "al. 1992 prockop", "1992 prockop &", "prockop & fertala 1998", "& fertala 1998 .", "fertala 1998 . fibril", "1998 . fibril formation", ". fibril formation is", "fibril formation is stabilized", "formation is stabilized by", "is stabilized by lysyl", "stabilized by lysyl oxidase", "by lysyl oxidase catalyzed", "lysyl oxidase catalyzed crosslinks", "oxidase catalyzed crosslinks between", "catalyzed crosslinks between adjacent", "crosslinks between adjacent molecules", "adjacent molecules siegel", "molecules siegel &", "siegel & fu", "& fu 1976", "the biosynthesis of collagen is", "biosynthesis of collagen is a", "of collagen is a multistep", "collagen is a multistep process.", "is a multistep process. collagen", "a multistep process. collagen propeptides", "multistep process. collagen propeptides are", "process. collagen propeptides are cotranslationally", "collagen propeptides are cotranslationally translocated", "propeptides are cotranslationally translocated into", "are cotranslationally translocated into the", "cotranslationally translocated into the er", "translocated into the er lumen.", "into the er lumen. propeptides", "the er lumen. propeptides undergo", "er lumen. propeptides undergo a", "lumen. propeptides undergo a number", "propeptides undergo a number of", "undergo a number of post", "a number of post translational", "number of post translational modifications.", "of post translational modifications. proline", "post translational modifications. proline and", "translational modifications. proline and lysine", "modifications. proline and lysine residues", "proline and lysine residues may", "and lysine residues may be", "lysine residues may be hydroxylated", "residues may be hydroxylated by", "may be hydroxylated by prolyl", "be hydroxylated by prolyl 3", "prolyl 3 prolyl", "3 prolyl 4", "prolyl 4 and lysyl", "4 and lysyl hydroxylases.", "and lysyl hydroxylases. 4 hydroxyproline", "lysyl hydroxylases. 4 hydroxyproline is", "hydroxylases. 4 hydroxyproline is essential", "4 hydroxyproline is essential for", "hydroxyproline is essential for intramolecular", "is essential for intramolecular hydrogen", "essential for intramolecular hydrogen bonding", "for intramolecular hydrogen bonding and", "intramolecular hydrogen bonding and stability", "hydrogen bonding and stability of", "bonding and stability of the", "and stability of the triple", "stability of the triple helical", "of the triple helical collagenous", "the triple helical collagenous domain.", "triple helical collagenous domain. in", "helical collagenous domain. in fibril", "collagenous domain. in fibril forming", "domain. in fibril forming collagens", "in fibril forming collagens approximately", "fibril forming collagens approximately 50%", "forming collagens approximately 50% of", "collagens approximately 50% of prolines", "approximately 50% of prolines are", "50% of prolines are 4", "of prolines are 4 hydroxylated", "are 4 hydroxylated the", "4 hydroxylated the extent", "hydroxylated the extent of", "the extent of this and", "extent of this and of", "of this and of 3", "this and of 3 hydroxyproline", "and of 3 hydroxyproline and", "of 3 hydroxyproline and lysine", "3 hydroxyproline and lysine hydroxylation", "hydroxyproline and lysine hydroxylation varies", "and lysine hydroxylation varies between", "lysine hydroxylation varies between tissues", "hydroxylation varies between tissues and", "varies between tissues and collagen", "between tissues and collagen types", "and collagen types kivirikko", "collagen types kivirikko et", "types kivirikko et al.", "et al. 1972 1992", "al. 1972 1992 .", "1972 1992 . hydroxylysine", "1992 . hydroxylysine molecules can", ". hydroxylysine molecules can form", "hydroxylysine molecules can form cross", "molecules can form cross links", "can form cross links between", "form cross links between collagen", "cross links between collagen molecules", "links between collagen molecules in", "between collagen molecules in fibrils", "molecules in fibrils and", "in fibrils and are", "fibrils and are sites", "and are sites for glycosyl", "sites for glycosyl and", "for glycosyl and galactosylation.", "glycosyl and galactosylation. collagen", "and galactosylation. collagen peptides all", "galactosylation. collagen peptides all have", "collagen peptides all have non", "peptides all have non collagenous", "all have non collagenous domains", "non collagenous domains collagens", "collagenous domains collagens within", "domains collagens within the", "collagens within the subclasses have", "within the subclasses have common", "the subclasses have common chain", "subclasses have common chain structures.", "have common chain structures. these", "common chain structures. these non", "chain structures. these non collagenous", "structures. these non collagenous domains", "these non collagenous domains have", "non collagenous domains have regulatory", "collagenous domains have regulatory functions", "have regulatory functions some", "regulatory functions some are", "functions some are biologically", "some are biologically active when", "are biologically active when cleaved", "biologically active when cleaved from", "active when cleaved from the", "when cleaved from the main", "cleaved from the main peptide", "from the main peptide chain.", "the main peptide chain. fibrillar", "main peptide chain. fibrillar collagens", "peptide chain. fibrillar collagens all", "chain. fibrillar collagens all have", "fibrillar collagens all have a", "collagens all have a large", "all have a large triple", "have a large triple helical", "a large triple helical domain", "triple helical domain col1", "domain col1 bordered", "col1 bordered by n", "bordered by n and c", "by n and c terminal", "n and c terminal extensions", "c terminal extensions called", "terminal extensions called the", "extensions called the n", "called the n and c", "the n and c propeptides", "and c propeptides which", "c propeptides which are", "propeptides which are cleaved", "which are cleaved prior to", "are cleaved prior to formation", "cleaved prior to formation of", "prior to formation of the", "to formation of the collagen", "formation of the collagen fibril.", "of the collagen fibril. the", "the collagen fibril. the c", "collagen fibril. the c propeptide", "the c propeptide also", "c propeptide also called", "propeptide also called the", "also called the nc1 domain", "the nc1 domain is", "nc1 domain is highly", "domain is highly conserved.", "is highly conserved. it directs", "highly conserved. it directs chain", "conserved. it directs chain association", "it directs chain association during", "directs chain association during intracellular", "chain association during intracellular assembly", "association during intracellular assembly of", "during intracellular assembly of the", "intracellular assembly of the procollagen", "assembly of the procollagen molecule", "of the procollagen molecule from", "the procollagen molecule from three", "procollagen molecule from three collagen", "molecule from three collagen propeptide", "from three collagen propeptide alpha", "three collagen propeptide alpha chains", "propeptide alpha chains hulmes", "alpha chains hulmes 2002", "chains hulmes 2002 .", "hulmes 2002 . the n", "2002 . the n propeptide", ". the n propeptide has", "the n propeptide has a", "n propeptide has a short", "propeptide has a short linker", "a short linker nc2", "linker nc2 connecting", "nc2 connecting the main", "connecting the main triple helix", "the main triple helix to", "main triple helix to a", "triple helix to a short", "helix to a short minor", "to a short minor one", "short minor one col2", "one col2 and", "col2 and a globular", "and a globular n terminal", "a globular n terminal region", "globular n terminal region nc3.", "n terminal region nc3. nc3", "terminal region nc3. nc3 domains", "region nc3. nc3 domains are", "nc3. nc3 domains are variable", "nc3 domains are variable both", "domains are variable both in", "are variable both in size", "variable both in size and", "both in size and the", "in size and the domains", "size and the domains they", "and the domains they contain.

collagen", "the domains they contain.

collagen propeptides", "domains they contain.

collagen propeptides typically", "they contain.

collagen propeptides typically undergo", "contain.

collagen propeptides typically undergo a", "propeptides typically undergo a number", "typically undergo a number of", "proline and lysine residues are", "and lysine residues are hydroxylated", "lysine residues are hydroxylated by", "residues are hydroxylated by prolyl", "are hydroxylated by prolyl 3", "triple helical collagenous domain. prolyl", "helical collagenous domain. prolyl 4", "collagenous domain. prolyl 4 hydroxylase", "domain. prolyl 4 hydroxylase may", "prolyl 4 hydroxylase may also", "4 hydroxylase may also have", "hydroxylase may also have a", "may also have a role", "also have a role in", "have a role in alpha", "a role in alpha chain", "role in alpha chain association", "in alpha chain association as", "alpha chain association as no", "chain association as no association", "association as no association of", "as no association of the", "no association of the c", "association of the c propeptides", "of the c propeptides of", "the c propeptides of type", "c propeptides of type xii", "propeptides of type xii collagen", "of type xii collagen was", "type xii collagen was seen", "xii collagen was seen in", "collagen was seen in the", "was seen in the presence", "seen in the presence of", "in the presence of prolyl", "the presence of prolyl 4", "presence of prolyl 4 hydroxylase", "of prolyl 4 hydroxylase inhibitors", "4 hydroxylase inhibitors mazzorana", "hydroxylase inhibitors mazzorana et", "inhibitors mazzorana et al.", "et al. 1993 1996", "al. 1993 1996 .", "1993 1996 . in", "1996 . in fibril forming", ". in fibril forming collagens", "the extent of this is", "extent of this is species", "of this is species dependent", "is species dependent lower", "species dependent lower hydroxylation", "dependent lower hydroxylation correlating", "lower hydroxylation correlating with lower", "hydroxylation correlating with lower ambient", "correlating with lower ambient temperature", "with lower ambient temperature and", "lower ambient temperature and thermal", "ambient temperature and thermal stability", "and thermal stability cohen", "thermal stability cohen solal", "stability cohen solal et", "cohen solal et al. 1986", "et al. 1986 notbohm", "al. 1986 notbohm et", "1986 notbohm et al.", "notbohm et al. 1992 .", "et al. 1992 . similarly", "al. 1992 . similarly the", "1992 . similarly the extent", ". similarly the extent of", "similarly the extent of 3", "the extent of 3 hydroxyproline", "extent of 3 hydroxyproline and", "kivirikko et al. 1992 .", "et al. 1992 . hydroxylysine", "al. 1992 . hydroxylysine molecules", "for glycosyl and galactosylation.

collagen", "glycosyl and galactosylation.

collagen molecules", "and galactosylation.

collagen molecules fold and", "galactosylation.

collagen molecules fold and assemble", "molecules fold and assemble through", "fold and assemble through a", "and assemble through a series", "assemble through a series of", "through a series of distinct", "a series of distinct intermediates", "of distinct intermediates bulleid", "distinct intermediates bulleid 1996", "intermediates bulleid 1996 .", "bulleid 1996 . individual collagen", "1996 . individual collagen polypeptide", ". individual collagen polypeptide chains", "individual collagen polypeptide chains are", "collagen polypeptide chains are translocated", "polypeptide chains are translocated co", "chains are translocated co translationally", "are translocated co translationally across", "translocated co translationally across the", "co translationally across the membrane", "translationally across the membrane of", "across the membrane of the", "the membrane of the endoplasmic", "membrane of the endoplasmic reticulum", "the endoplasmic reticulum er", "endoplasmic reticulum er .", "reticulum er . intra", "er . intra chain disulfide", ". intra chain disulfide bonds", "intra chain disulfide bonds are", "chain disulfide bonds are formed", "disulfide bonds are formed within", "bonds are formed within the", "are formed within the n", "formed within the n propeptide", "the n propeptide and", "n propeptide and hydroxylation", "propeptide and hydroxylation of", "and hydroxylation of proline and", "hydroxylation of proline and lysine", "of proline and lysine residues", "proline and lysine residues occurs", "and lysine residues occurs within", "lysine residues occurs within the", "residues occurs within the triple", "occurs within the triple helical", "within the triple helical domain", "triple helical domain kivirikko", "helical domain kivirikko et", "domain kivirikko et al.", "et al. 1992 . when", "al. 1992 . when the", "1992 . when the peptide", ". when the peptide chain", "when the peptide chain is", "the peptide chain is fully", "peptide chain is fully translocated", "chain is fully translocated into", "is fully translocated into the", "fully translocated into the er", "translocated into the er lumen", "into the er lumen the", "the er lumen the c", "er lumen the c propeptide", "lumen the c propeptide folds", "c propeptide folds the", "propeptide folds the conformation", "folds the conformation being", "the conformation being stabilized by", "conformation being stabilized by intra", "being stabilized by intra chain", "stabilized by intra chain disulfide", "by intra chain disulfide bonds", "chain disulfide bonds doege", "disulfide bonds doege and", "bonds doege and fessler", "doege and fessler 1986 .", "and fessler 1986 . pro", "fessler 1986 . pro alpha", "1986 . pro alpha chains", ". pro alpha chains associate", "pro alpha chains associate via", "alpha chains associate via the", "chains associate via the c", "associate via the c propeptides", "the c propeptides byers", "c propeptides byers et", "propeptides byers et al.", "et al. 1975 bachinger", "al. 1975 bachinger et", "1975 bachinger et al.", "al. 1978 or", "1978 or nc2", "or nc2 domains for facit", "nc2 domains for facit family", "domains for facit family collagens", "facit family collagens boudko", "family collagens boudko et", "collagens boudko et al.", "et al. 2008 to", "al. 2008 to form", "2008 to form an", "to form an initial trimer", "form an initial trimer which", "an initial trimer which can", "initial trimer which can be", "trimer which can be stabilized", "which can be stabilized by", "can be stabilized by the", "be stabilized by the formation", "stabilized by the formation of", "by the formation of inter", "the formation of inter chain", "formation of inter chain disulfide", "of inter chain disulfide bonds", "chain disulfide bonds schofield", "disulfide bonds schofield et", "bonds schofield et al.", "et al. 1974 olsen", "al. 1974 olsen et", "1974 olsen et al.", "al. 1976 though", "1976 though these", "though these are not a", "these are not a prerequisite", "are not a prerequisite for", "not a prerequisite for further", "a prerequisite for further folding", "for further folding bulleid", "further folding bulleid et", "folding bulleid et al.", "bulleid et al. 1996 .", "et al. 1996 . the", "al. 1996 . the triple", "1996 . the triple helix", ". the triple helix then", "the triple helix then nucleates", "triple helix then nucleates and", "helix then nucleates and folds", "then nucleates and folds in", "nucleates and folds in a", "and folds in a c", "in a c to", "a c to n", "to n direction. the", "n direction. the association", "direction. the association of the", "the association of the individual", "association of the individual chains", "of the individual chains and", "the individual chains and subsequent", "individual chains and subsequent triple", "chains and subsequent triple helix", "and subsequent triple helix formation", "subsequent triple helix formation are", "triple helix formation are distinct", "helix formation are distinct steps", "are distinct steps bachinger", "distinct steps bachinger et", "steps bachinger et al.", "bachinger et al. 1980 .", "et al. 1980 . the", "al. 1980 . the n", "1980 . the n propeptides", ". the n propeptides associate", "the n propeptides associate and", "n propeptides associate and in", "propeptides associate and in some", "associate and in some cases", "and in some cases form", "in some cases form inter", "some cases form inter chain", "cases form inter chain disulfide", "form inter chain disulfide bonds", "chain disulfide bonds bruckner", "disulfide bonds bruckner et", "bonds bruckner et al.", "bruckner et al. 1978", "et al. 1978 .", "al. 1978 . procollagen", "1978 . procollagen is released", ". procollagen is released via", "procollagen is released via carriers", "is released via carriers into", "released via carriers into the", "via carriers into the exracellular", "carriers into the exracellular space", "the exracellular space canty", "exracellular space canty &", "space canty & kadler", "canty & kadler 2005 .", "& kadler 2005 . fibrillar", "kadler 2005 . fibrillar procollagens", "2005 . fibrillar procollagens undergo", ". fibrillar procollagens undergo removal", "fibrillar procollagens undergo removal of", "procollagens undergo removal of the", "undergo removal of the c", "of the c and", "the c and n", "c and n propeptides", "and n propeptides by procollagen", "n propeptides by procollagen c", "propeptides by procollagen c and", "by procollagen c and n", "procollagen c and n proteinases", "c and n proteinases respectively", "n proteinases respectively both", "proteinases respectively both zn2+", "respectively both zn2+ dependent", "both zn2+ dependent metalloproteinases. propeptide", "zn2+ dependent metalloproteinases. propeptide processing", "dependent metalloproteinases. propeptide processing is", "metalloproteinases. propeptide processing is a", "propeptide processing is a required", "processing is a required step", "is a required step for", "a required step for normal", "required step for normal collagen", "step for normal collagen i", "for normal collagen i and", "normal collagen i and iii", "collagen i and iii fibril", "i and iii fibril formation", "iii fibril formation but", "fibril formation but collagens", "formation but collagens can", "but collagens can retain some", "collagens can retain some or", "can retain some or all", "retain some or all of", "some or all of their", "or all of their non", "all of their non collagenous", "of their non collagenous propeptides.", "their non collagenous propeptides. retained", "non collagenous propeptides. retained collagen", "collagenous propeptides. retained collagen type", "propeptides. retained collagen type v", "retained collagen type v and", "collagen type v and xi", "type v and xi n", "v and xi n propeptides", "and xi n propeptides contribute", "xi n propeptides contribute to", "n propeptides contribute to the", "propeptides contribute to the control", "contribute to the control of", "to the control of fibril", "the control of fibril growth", "control of fibril growth by", "of fibril growth by sterically", "fibril growth by sterically limiting", "growth by sterically limiting lateral", "by sterically limiting lateral molecule", "sterically limiting lateral molecule addition", "lateral molecule addition fichard", "molecule addition fichard et", "addition fichard et al.", "fichard et al. 1995 .", "et al. 1995 . processed", "al. 1995 . processed fibrillar", "1995 . processed fibrillar procollagen", ". processed fibrillar procollagen is", "processed fibrillar procollagen is termed", "fibrillar procollagen is termed tropocollagen", "is termed tropocollagen which", "termed tropocollagen which is", "tropocollagen which is considered", "which is considered to be", "is considered to be the", "considered to be the unit", "to be the unit of", "be the unit of higher", "the unit of higher order", "unit of higher order fibrils", "of higher order fibrils and", "higher order fibrils and fibres.", "order fibrils and fibres. tropocollagens", "fibrils and fibres. tropocollagens of", "and fibres. tropocollagens of the", "fibres. tropocollagens of the fibril", "tropocollagens of the fibril forming", "of the fibril forming collagens", "the fibril forming collagens i", "forming collagens i ii", "i ii iii", "ii iii v", "iii v and xi", "v and xi sponteneously aggregate", "and xi sponteneously aggregate in", "xi sponteneously aggregate in vitro", "sponteneously aggregate in vitro in", "aggregate in vitro in a", "in vitro in a manner", "vitro in a manner that", "in a manner that has", "a manner that has been", "manner that has been compared", "that has been compared with", "has been compared with crystallization", "compared with crystallization commencing", "with crystallization commencing with", "crystallization commencing with a", "commencing with a nucleation event", "with a nucleation event followed", "a nucleation event followed by", "nucleation 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al.", "et al. 1997", "1997 gurung", "gurung et al.", "et al. 2003", "2003 guo", "guo et al.", "et al. 1999", "1999 vanhaesebroeck", "vanhaesebroeck et al.", "1997 tolias", "tolias et al.", "et al. 1998", "1998 schaletzky", "schaletzky et al.", "2003 kim", "kim et al.", "et al. 2002", "2002 clarke", "clarke et al.", "et al. 2010", "al. 2010 .", "2010 . many", ". many of", "many of the", "of the phosphatidylinositol", "the phosphatidylinositol phosphatases", "phosphatidylinositol phosphatases that", "phosphatases that act", "that act at", "act at the", "plasma membrane belong", "membrane belong to", "belong to the", "to the myotubularin", "the myotubularin family.", "myotubularin family. enzymatically", "family. enzymatically inactive", "enzymatically inactive myotubularin", "inactive myotubularin family", "myotubularin family members", "family members can", "members can heterodimerize", "can heterodimerize with", "heterodimerize with catalytically", "with catalytically active", 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"2003 guo et al.", "et al. 1999 vanhaesebroeck", "al. 1999 vanhaesebroeck et", "1999 vanhaesebroeck et al.", "et al. 1997 tolias", "al. 1997 tolias et", "1997 tolias et al.", "et al. 1998 schaletzky", "al. 1998 schaletzky et", "1998 schaletzky et al.", "et al. 2003 kim", "al. 2003 kim et", "2003 kim et al.", "et al. 2002 clarke", "al. 2002 clarke et", "2002 clarke et al.", "clarke et al. 2010 .", "et al. 2010 . many", "al. 2010 . many of", "2010 . many of the", ". many of the phosphatidylinositol", "many of the phosphatidylinositol phosphatases", "of the phosphatidylinositol phosphatases that", "the phosphatidylinositol phosphatases that act", "phosphatidylinositol phosphatases that act at", "phosphatases that act at the", "that act at the plasma", "act at the plasma membrane", "at the plasma membrane belong", "the plasma membrane belong to", "plasma membrane belong to the", "membrane belong to the myotubularin", "belong to the myotubularin family.", "to the myotubularin family. enzymatically", "the myotubularin family. enzymatically inactive", "myotubularin family. enzymatically inactive myotubularin", "family. enzymatically inactive myotubularin family", "enzymatically inactive myotubularin family members", "inactive myotubularin family members can", "myotubularin family members can heterodimerize", "family members can heterodimerize with", "members can heterodimerize with catalytically", "can heterodimerize with catalytically active", "heterodimerize with catalytically active mytotubularins", "with catalytically active mytotubularins to", "catalytically active mytotubularins to regulate", "active mytotubularins to regulate their", "mytotubularins to regulate their stability", "regulate their stability activity", "their stability activity and/or", "stability activity and/or substrate", "and/or substrate specificity berger", "substrate specificity berger et", "specificity berger et al.", "et al. 2006 zou", "al. 2006 zou et", "2006 zou et al.", "zou et al. 2012 ." ] }, { "record_id": "GLY_000594_1_81", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1660514", "r hsa", "hsa 1660514", "r hsa 1660514" ] }, { "record_id": "GLY_000594_1_81", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pips", "pips at", "at the", "the golgi", "golgi membrane", "synthesis of pips", "of pips at", "pips at the", "at the golgi", "the golgi membrane", "synthesis of pips at", "of pips at the", "pips at the golgi", "at the golgi membrane", "synthesis of pips at the", "of pips at the golgi", "pips at the golgi membrane", "phosphatidylinositol 4", "4 phosphate", "is primarily", "primarily generated", "generated from", "from phosphorylation", "phosphorylation of", "of phosphatidylinositol", "pi .", "other phosphoinositides", "phosphoinositides are", "are also", "also generated", "generated by", "by the", "the action", "action of", "of various", "various 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generated", "are also generated by", "also generated by the", "generated by the action", "by the action of", "the action of various", "action of various kinases", "of various kinases and", "various kinases and phosphatases", "kinases and phosphatases such", "and phosphatases such as:", "phosphatases such as: phosphatidylinositol", "such as: phosphatidylinositol 3", "as: phosphatidylinositol 3 phosphate", "3 phosphate pi3p", "pi3p phosphatidylinositol", "phosphatidylinositol 3 4 bisphosphate", "4 bisphosphate pi", "bisphosphate pi 3", "pi 3 4 p2", "p2 phosphatidylinositol", "phosphatidylinositol 3 5 bisphosphate", "5 bisphosphate pi", "pi 3 5 p2", "p2 godi", "godi et al. 1999", "al. 1999 minogue", "1999 minogue et", "minogue et al. 2001", "al. 2001 rohde", "2001 rohde et", "rohde et al. 2003", "al. 2003 sbrissa", "2003 sbrissa et", "sbrissa et al. 2007", "al. 2007 sbrissa", "2007 sbrissa et", "sbrissa et al. 2008", "al. 2008 domin", "2008 domin et", "domin et al. 2000", "al. 2000 arcaro", "2000 arcaro et", "arcaro et al. 2000", "et al. 2000 .", "the golgi membrane phosphatidylinositol", "golgi membrane phosphatidylinositol 4", "membrane phosphatidylinositol 4 phosphate", "phosphatidylinositol 4 phosphate pi4p", "phosphate pi4p is", "pi4p is primarily generated", "is primarily generated from phosphorylation", "primarily generated from phosphorylation of", "generated from phosphorylation of phosphatidylinositol", "phosphorylation of phosphatidylinositol pi", "of phosphatidylinositol pi .", "pi . other phosphoinositides", ". other phosphoinositides are", "other phosphoinositides are also generated", "phosphoinositides are also generated by", "are also generated by the", "also generated by the action", "generated by the action of", "by the action of various", "the action of various kinases", "action of various kinases and", "of various kinases and phosphatases", "various kinases and phosphatases such", "kinases and phosphatases such as:", "and phosphatases such as: 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"al. 2007 cao et", "2007 cao et al.", "et al. 2008 arcaro", "al. 2008 arcaro et", "2008 arcaro et al.", "et al. 2000 kim", "al. 2000 kim et", "2000 kim et al.", "kim et al. 2002 ." ] }, { "record_id": "GLY_000594_1_84", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "166058", "r hsa", "hsa 166058", "r hsa 166058" ] }, { "record_id": "GLY_000594_1_84", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "myd88:mal tirap", "cascade initiated", "initiated on", "on plasma", "plasma membrane", "tirap cascade", "cascade initiated on", "initiated on plasma", "on plasma membrane", "myd88:mal tirap cascade", "tirap cascade initiated", "cascade initiated on plasma", "initiated on plasma membrane", "myd88:mal tirap cascade initiated", "tirap cascade initiated on", "cascade initiated on plasma membrane", "the first", "first known", "known downstream", "downstream component", "component of", "of tlr4", "tlr4 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"irak . recruitment of", ". recruitment of these", "recruitment of these protein", "of these protein kinases", "these protein kinases is", "protein kinases is accompanied", "kinases is accompanied by", "is accompanied by phosphorylation", "by phosphorylation which", "phosphorylation which in", "which in turn results", "in turn results in", "turn results in the", "results in the interaction", "in the interaction of", "the interaction of iraks", "interaction of iraks with", "of iraks with tnf", "iraks with tnf receptor", "with tnf receptor associated", "tnf receptor associated factor", "receptor associated factor 6", "factor 6 traf6", "6 traf6 .", "traf6 . the oligomerization", ". the oligomerization of", "the oligomerization of traf6", "oligomerization of traf6 activates", "of traf6 activates tak1", "activates tak1 a", "tak1 a member", "a member of the", "member of the map3", "of the map3 kinase", "the map3 kinase family", "kinase family and", "family and this", "and this leads to", "this leads to the", "leads to the activation", "to the activation of", "the activation of the", "activation of the ikb", "of the ikb kinases.", "the ikb kinases. these", "ikb kinases. these kinases", "these kinases in", "kinases in turn", "in turn phosphorylate", "turn phosphorylate ikb", "phosphorylate ikb leading", "ikb leading to", "leading to its proteolytic", "to its proteolytic degradation", "its proteolytic degradation and", "proteolytic degradation and the", "degradation and the translocation", "and the translocation of", "the translocation of nf", "translocation of nf kb", "of nf kb to", "nf kb to the", "kb to the nucleus.", "to the nucleus. concomitantly", "nucleus. concomitantly members", "concomitantly members of", "members of the activator", "of the activator protein", "the activator protein 1", "protein 1 ap", "1 ap 1", "1 transcription factor", "factor family jun", "family jun and", "and fos are", "fos are activated", "are activated and", "activated and both", "and both ap 1", "both ap 1 transcription", "ap 1 transcription factors", "1 transcription factors and", "transcription factors and nf", "factors and nf kb", "and nf kb are", "nf kb are required", "kb are required for", "are required for cytokine", "required for cytokine production", "cytokine production which", "production which in", "which in turn produces", "in turn produces downstream", "turn produces downstream inflammatory", "produces downstream inflammatory effects.", "the first known downstream component", "first known downstream component of", "known downstream component of tlr4", "downstream component of tlr4 and", "component of tlr4 and tlr2", "of tlr4 and tlr2 signaling", "tlr4 and tlr2 signaling is", "and tlr2 signaling is the", "tlr2 signaling is the adaptor", "signaling is the adaptor myd88.", "is the adaptor myd88. another", "the adaptor myd88. another adapter", "adaptor myd88. another adapter myd88", "myd88. another adapter myd88 adaptor", "another adapter myd88 adaptor like", "myd88 adaptor like mal", "like mal also", "mal also known as", "also known as tir domain", "known as tir domain containing", "as tir domain containing adaptor", "tir domain containing adaptor protein", "domain containing adaptor protein or", "containing adaptor protein or tirap", "protein or tirap has", "or tirap has also", "tirap has also been", "has also been described for", "also been described for tlr4", "been described for tlr4 and", "described for tlr4 and tlr2", "for tlr4 and tlr2 signaling.", "tlr4 and tlr2 signaling. myd88", "and tlr2 signaling. myd88 comprises", "tlr2 signaling. myd88 comprises an", "signaling. myd88 comprises an n", "myd88 comprises an n terminal", "comprises an n terminal death", "an n terminal death domain", "terminal death domain dd", "domain dd and", "dd and a c", "and a c terminal tir", "c terminal tir whereas", "terminal tir whereas mal", "tir whereas mal lacks", "whereas mal lacks the dd.", "mal lacks the dd. the", "lacks the dd. the tir", "the dd. the tir homotypic", "dd. the tir homotypic interactions", "the tir homotypic interactions bring", "tir homotypic interactions bring adapters", "homotypic interactions bring adapters into", "interactions bring adapters into contact", "bring adapters into contact with", "adapters into contact with the", "into contact with the activated", "contact with the activated tlrs", "the activated tlrs whereas", "activated tlrs whereas the", "tlrs whereas the dd", "whereas the dd modules recruit", "the dd modules recruit serine/threonine", "dd modules recruit serine/threonine kinases", "modules recruit serine/threonine kinases such", "recruit serine/threonine kinases such as", "serine/threonine kinases such as interleukin", "kinases such as interleukin 1", "such as interleukin 1 receptor", "as interleukin 1 receptor associated", "interleukin 1 receptor associated kinase", "receptor associated kinase irak", "associated kinase irak .", "kinase irak . recruitment", "irak . recruitment of these", ". recruitment of these protein", "recruitment of these protein kinases", "of these protein kinases is", "these protein kinases is accompanied", "protein kinases is accompanied by", "kinases is accompanied by phosphorylation", "accompanied by phosphorylation which", "by phosphorylation which in", "phosphorylation which in turn", "which in turn results in", "in turn results in the", "turn results in the interaction", "results in the interaction of", "in the interaction of iraks", "the interaction of iraks with", "interaction of iraks with tnf", "of iraks with tnf receptor", "iraks with tnf receptor associated", "with tnf receptor associated factor", "tnf receptor associated factor 6", "associated factor 6 traf6", "factor 6 traf6 .", "6 traf6 . the", "traf6 . the oligomerization of", ". the oligomerization of traf6", "the oligomerization of traf6 activates", "oligomerization of traf6 activates tak1", "traf6 activates tak1 a", "activates tak1 a member", "tak1 a member of", "a member of the map3", "member of the map3 kinase", "of the map3 kinase family", "map3 kinase family and", "kinase family and this", "family and this leads", "and this leads to the", "this leads to the activation", "leads to the activation of", "to the activation of the", "the activation of the ikb", "activation of the ikb kinases.", "of the ikb kinases. these", "the ikb kinases. these kinases", "kinases. these kinases in", "these kinases in turn", "in turn phosphorylate ikb", "phosphorylate ikb leading to", "ikb leading to its", "leading to its proteolytic degradation", "to its proteolytic degradation and", "its proteolytic degradation and the", "proteolytic degradation and the translocation", "degradation and the translocation of", "and the translocation of nf", "the translocation of nf kb", "translocation of nf kb to", "of nf kb to the", "nf kb to the nucleus.", "kb to the nucleus. concomitantly", "the nucleus. concomitantly members", "nucleus. concomitantly members of", "concomitantly members of the", "members of the activator protein", "of the activator protein 1", "activator protein 1 ap", "protein 1 ap 1", "ap 1 transcription factor", "1 transcription factor family", "transcription factor family jun", "factor family jun and", "family jun and fos", "jun and fos are", "and fos are activated", "are activated and both", "activated and both ap", "and both ap 1 transcription", "both ap 1 transcription factors", "ap 1 transcription factors and", "1 transcription factors and nf", "transcription factors and nf kb", "factors and nf kb are", "and nf kb are required", "nf kb are required for", "kb are required for cytokine", "are required for cytokine production", "for cytokine production which", "cytokine production which in", "production which in turn", "which in turn produces downstream", "in turn produces downstream inflammatory", "turn produces downstream inflammatory effects." ] }, { "record_id": "GLY_000594_1_85", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1660661", "r hsa", "hsa 1660661", "r hsa 1660661" ] }, { "record_id": "GLY_000594_1_85", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sphingolipid de", "de novo", "novo biosynthesis", "sphingolipid de novo", "de novo biosynthesis", "sphingolipid de novo biosynthesis", "glycosphingolipid biosynthesis", "biosynthesis is", "is based", "based on", "on salvage", "salvage of", "of sphingolipids", "sphingolipids and", "and de", "novo sphingolipid", "sphingolipid synthesis.", "synthesis. sphingoid", "sphingoid 1", "1 phosphate", "phosphate signalling", "signalling molecules", "molecules are", "are synthesized", "synthesized through", "through the", "the same", "same pathway", "which starts", "starts with", "with the", "the transfer", "transfer of", "of a", "a fatty", "fatty acid", "acid onto", "onto serine.", "serine. the", "the diversity", "diversity of", "of products", "products results", "results from", "from 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pathway", "same pathway which", "pathway which starts", "which starts with the", "starts with the transfer", "with the transfer of", "the transfer of a", "transfer of a fatty", "of a fatty acid", "a fatty acid onto", "fatty acid onto serine.", "acid onto serine. the", "onto serine. the diversity", "serine. the diversity of", "the diversity of products", "diversity of products results", "of products results from", "products results from later", "results from later dehydrogenation", "from later dehydrogenation or", "later dehydrogenation or hydroxylation", "dehydrogenation or hydroxylation of", "or hydroxylation of fatty", "hydroxylation of fatty acid", "of fatty acid moieties", "acid moieties as", "moieties as well", "as well as the", "well as the usage", "as the usage of", "the usage of fatty", "usage of fatty acids", "of fatty acids of", "fatty acids of different", "acids of different lengths.", "of different lengths. biosynthesis", "different lengths. biosynthesis takes", "lengths. biosynthesis takes place", "biosynthesis takes place in", "takes place in the", "place in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum lumen", "endoplasmic reticulum lumen and", "reticulum lumen and the", "lumen and the cytosol.", "and the cytosol. lipophilic", "the cytosol. lipophilic products", "cytosol. lipophilic products are", "lipophilic products are transported", "products are transported to", "are transported to other", "transported to other membranes", "to other membranes via", "other membranes via a", "membranes via a specialized", "via a specialized transporter", "specialized transporter cert1", "cert1 or the", "or the secretory pathway.", "the secretory pathway. soluble", "secretory pathway. soluble sphingoid", "pathway. soluble sphingoid 1", "soluble sphingoid 1 phosphates", "sphingoid 1 phosphates are", "1 phosphates are exported", "phosphates are exported by", "are exported by multiple", "exported by multiple transporters", "by multiple transporters in", "multiple transporters in the", "transporters in the plasma", "in the plasma membrane", "plasma membrane reviewed", "membrane reviewed by", "reviewed by merrill 2002", "merrill 2002 gault", "2002 gault et", "gault et al. 2010", "et al. 2010 .", "glycosphingolipid biosynthesis is based on", "biosynthesis is based on salvage", "is based on salvage of", "based on salvage of sphingolipids", "on salvage of sphingolipids and", "salvage of sphingolipids and de", "of sphingolipids and de novo", "sphingolipids and de novo sphingolipid", "and de novo sphingolipid synthesis.", "de novo sphingolipid synthesis. sphingoid", "novo sphingolipid synthesis. sphingoid 1", "sphingolipid synthesis. sphingoid 1 phosphate", "synthesis. sphingoid 1 phosphate signalling", "sphingoid 1 phosphate signalling molecules", "1 phosphate signalling molecules are", "phosphate signalling molecules are synthesized", "signalling molecules are synthesized through", "molecules are synthesized through the", "are synthesized through the same", "synthesized through the same pathway", "the same pathway which", "same pathway which starts", "pathway which starts with", "which starts with the transfer", "starts with the transfer of", "with the transfer of a", "the transfer of a fatty", "transfer of a fatty acid", "of a fatty acid onto", "a fatty acid onto serine.", "fatty acid onto serine. the", "acid onto serine. the diversity", "onto serine. the diversity of", "serine. the diversity of products", "the diversity of products results", "diversity of products results from", "of products results from later", "products results from later dehydrogenation", "results from later dehydrogenation or", "from later dehydrogenation or hydroxylation", "later dehydrogenation or hydroxylation of", "dehydrogenation or hydroxylation of fatty", "or hydroxylation of fatty acid", "hydroxylation of fatty acid moieties", "fatty acid moieties as", "acid moieties as well", "moieties as well as", "as well as the usage", "well as the usage of", "as the usage of fatty", "the usage of fatty acids", "usage of fatty acids of", "of fatty acids of different", "fatty acids of different lengths.", "acids of different lengths. biosynthesis", "of different lengths. biosynthesis takes", "different lengths. biosynthesis takes place", "lengths. biosynthesis takes place in", "biosynthesis takes place in the", "takes place in the endoplasmic", "place in the endoplasmic reticulum", "in the endoplasmic reticulum lumen", "the endoplasmic reticulum lumen and", "endoplasmic reticulum lumen and the", "reticulum lumen and the cytosol.", "lumen and the cytosol. lipophilic", "and the cytosol. lipophilic products", "the cytosol. lipophilic products are", "cytosol. lipophilic products are transported", "lipophilic products are transported to", "products are transported to other", "are transported to other membranes", "transported to other membranes via", "to other membranes via a", "other membranes via a specialized", "membranes via a specialized transporter", "a specialized transporter cert1", "transporter cert1 or", "cert1 or the secretory", "or the secretory pathway. soluble", "the secretory pathway. soluble sphingoid", "secretory pathway. soluble sphingoid 1", "pathway. soluble sphingoid 1 phosphates", "soluble sphingoid 1 phosphates are", "sphingoid 1 phosphates are exported", "1 phosphates are exported by", "phosphates are exported by multiple", "are exported by multiple transporters", "exported by multiple transporters in", "by multiple transporters in the", "multiple transporters in the plasma", "transporters in the plasma membrane", "the plasma membrane reviewed", "plasma membrane reviewed by", "membrane reviewed by merrill", "by merrill 2002 gault", "merrill 2002 gault et", "2002 gault et al.", "gault et al. 2010 ." ] }, { "record_id": "GLY_000594_1_86", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "166166", "r hsa", "hsa 166166", "r hsa 166166" ] }, { "record_id": "GLY_000594_1_86", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "myd88 independent", "independent tlr4", "tlr4 cascade", "myd88 independent tlr4", "independent tlr4 cascade", "myd88 independent tlr4 cascade", "the myd88", "independent signaling", "signaling pathway", "pathway is", "is shared", "shared by", "by tlr3", "tlr3 and", "and tlr4", "tlr4 cascades.", "cascades. tir", "tir domain", "domain containing", "containing adapter", "adapter inducing", "inducing interferon", "interferon beta", "trif or", "or ticam1", "is a", "a key", "key adapter", "adapter molecule", "molecule in", "in transducing", "transducing signals", "signals from", "from tlr3", "tlr4 in", "in a", "a myd88", "independent manner", "yamamoto m", "m et", "et al.", "al. 2003a", "2003a .", ". trif", "trif is", "is recruited", "recruited to", "to the", "the ligand", "ligand stimulated", "stimulated tlr3", "tlr3 or", "or 4", "4 complex", "complex via", "via its", "its tir", "tir domain.", "domain. tlr3", "tlr3 directly", "directly binds", "binds trif", "oshiumi h", "h et", "et al", "al 2003", "2003 .", ". in", "in contrast", "the tlr4", "tlr4 mediated", "mediated signaling", "pathway requires", "requires two", "two adapter", "adapter molecules", "trif related", "related adapter", "molecule or", "or ticam2", "and trif.", "trif. tram", "tram ticam2", "is thought", "thought to", "to bridge", "bridge the", "the activated", "activated tlr4", "tlr4 complex", "complex and", "and trif", "al. 2003b", "tanimura n", "n et", "al. 2008", "kagan lc", "lc et", "2008 .

trif", ".

trif recruitment", "recruitment to", "the tlr", "tlr complex", "complex stimulates", "stimulates distinct", "distinct pathways", "pathways leading", "leading to", "the production", "production of", "of type", "type i", "i interferons", "and pro", "pro inflammatory", "inflammatory cytokines", "cytokines and", "and to", "the induction", "induction of", "of programmed", "programmed cell", "cell death.", "the myd88 independent", "myd88 independent signaling", "independent signaling pathway", "signaling pathway is", "pathway is shared", "is shared by", "shared by tlr3", "by tlr3 and", "tlr3 and tlr4", "and tlr4 cascades.", "tlr4 cascades. tir", "cascades. tir domain", "tir domain containing", "domain containing adapter", "containing adapter inducing", "adapter inducing interferon", "inducing interferon beta", "beta trif", "trif or ticam1", "ticam1 is", "is a key", "a key adapter", "key adapter molecule", "adapter molecule in", "molecule in transducing", "in transducing signals", "transducing signals from", "signals from tlr3", "from tlr3 and", "and tlr4 in", "tlr4 in a", "in a myd88", "a myd88 independent", "myd88 independent manner", "manner yamamoto", "yamamoto m et", "m et al.", "et al. 2003a", "al. 2003a .", "2003a . trif", ". trif is", "trif is recruited", "is recruited to", "recruited to the", "to the ligand", "the ligand stimulated", "ligand stimulated tlr3", "stimulated tlr3 or", "tlr3 or 4", "or 4 complex", "4 complex via", "complex via its", "via its tir", "its tir domain.", "tir domain. tlr3", "domain. tlr3 directly", "tlr3 directly binds", "directly binds trif", "trif oshiumi", "oshiumi h et", "h et al", "et al 2003", "al 2003 .", "2003 . in", ". in contrast", "contrast the", "the tlr4 mediated", "tlr4 mediated signaling", "mediated signaling pathway", "signaling pathway requires", "pathway requires two", "requires two adapter", "two adapter molecules", "molecules tram", "tram trif", "trif related adapter", "related adapter molecule", "adapter molecule or", "molecule or ticam2", "ticam2 and", "and trif. tram", "trif. tram ticam2", "ticam2 is", "is thought to", "thought to bridge", "to bridge the", "bridge the activated", "the activated tlr4", "activated tlr4 complex", "tlr4 complex and", "complex and trif", "trif yamamoto", "et al. 2003b", "2003b tanimura", "tanimura n et", "n et al.", "et al. 2008", "2008 kagan", "kagan lc et", "lc et al.", "al. 2008 .

trif", "2008 .

trif recruitment", ".

trif recruitment to", "recruitment to the", "to the tlr", "the tlr complex", "tlr complex stimulates", "complex stimulates distinct", "stimulates distinct pathways", "distinct pathways leading", "pathways leading to", "leading to the", "to the production", "the production of", "production of type", "of type i", "type i interferons", "interferons ifns", "ifns and", "and pro inflammatory", "pro inflammatory cytokines", "inflammatory cytokines and", "cytokines and to", "and to the", "to the induction", "the induction of", "induction of programmed", "of programmed cell", "programmed cell death.", "the myd88 independent signaling", "myd88 independent signaling pathway", "independent signaling pathway is", "signaling pathway is shared", "pathway is shared by", "is shared by tlr3", "shared by tlr3 and", "by tlr3 and tlr4", "tlr3 and tlr4 cascades.", "and tlr4 cascades. tir", "tlr4 cascades. tir domain", "cascades. tir domain containing", "tir domain containing adapter", "domain containing adapter inducing", "containing adapter inducing interferon", "adapter inducing interferon beta", "interferon beta trif", "beta trif or", "or ticam1 is", "ticam1 is a", "is a key adapter", "a key adapter molecule", "key adapter molecule in", "adapter molecule in transducing", "molecule in transducing signals", "in transducing signals from", "transducing signals from tlr3", "signals from tlr3 and", "from tlr3 and tlr4", "tlr3 and tlr4 in", "and tlr4 in a", "tlr4 in a myd88", "in a myd88 independent", "a myd88 independent manner", "independent manner yamamoto", "manner yamamoto m", "yamamoto m et al.", "m et al. 2003a", "et al. 2003a .", "al. 2003a . trif", "2003a . trif is", ". trif is recruited", "trif is recruited to", "is recruited to the", "recruited to the ligand", "to the ligand stimulated", "the ligand stimulated tlr3", "ligand stimulated tlr3 or", "stimulated tlr3 or 4", "tlr3 or 4 complex", "or 4 complex via", "4 complex via its", "complex via its tir", "via its tir domain.", "its tir domain. tlr3", "tir domain. tlr3 directly", "domain. tlr3 directly binds", "tlr3 directly binds trif", "binds trif oshiumi", "trif oshiumi h", "oshiumi h et al", "h et al 2003", "et al 2003 .", "al 2003 . in", "2003 . in contrast", "in contrast the", "contrast the tlr4", "the tlr4 mediated signaling", "tlr4 mediated signaling pathway", "mediated signaling pathway requires", "signaling pathway requires two", "pathway requires two adapter", "requires two adapter molecules", "adapter molecules tram", "tram trif related", "trif related adapter molecule", "related adapter molecule or", "adapter molecule or ticam2", "or ticam2 and", "ticam2 and trif.", "and trif. tram ticam2", "tram ticam2 is", "ticam2 is thought", "is thought to bridge", "thought to bridge the", "to bridge the activated", "bridge the activated tlr4", "the activated tlr4 complex", "activated tlr4 complex and", "tlr4 complex and trif", "and trif yamamoto", "trif yamamoto m", "m et al. 2003b", "al. 2003b tanimura", "2003b tanimura n", "tanimura n et al.", "n et al. 2008", "al. 2008 kagan", "2008 kagan lc", "kagan lc et al.", "lc et al. 2008", "et al. 2008 .

trif", "al. 2008 .

trif recruitment", "2008 .

trif recruitment to", ".

trif recruitment to the", "recruitment to the tlr", "to the tlr complex", "the tlr complex stimulates", "tlr complex stimulates distinct", "complex stimulates distinct pathways", "stimulates distinct pathways leading", "distinct pathways leading to", "pathways leading to the", "leading to the production", "to the production of", "the production of type", "production of type i", "of type i interferons", "i interferons ifns", "ifns and pro", "and pro inflammatory cytokines", "pro inflammatory cytokines and", "inflammatory cytokines and to", "cytokines and to the", "and to the induction", "to the induction of", "the induction of programmed", "induction of programmed cell", "of programmed cell death.", "the myd88 independent signaling pathway", "myd88 independent signaling pathway is", "independent signaling pathway is shared", "signaling pathway is shared by", "pathway is shared by tlr3", "is shared by tlr3 and", "shared by tlr3 and tlr4", "by tlr3 and tlr4 cascades.", "tlr3 and tlr4 cascades. tir", "and tlr4 cascades. tir domain", "tlr4 cascades. tir domain containing", "cascades. tir domain containing adapter", "tir domain containing adapter inducing", "domain containing adapter inducing interferon", "containing adapter inducing interferon beta", "inducing interferon beta trif", "interferon beta trif or", "beta trif or ticam1", "trif or ticam1 is", "or ticam1 is a", "ticam1 is a key", "is a key adapter molecule", "a key adapter molecule in", "key adapter molecule in transducing", "adapter molecule in transducing signals", "molecule in transducing signals from", "in transducing signals from tlr3", "transducing signals from tlr3 and", "signals from tlr3 and tlr4", "from tlr3 and tlr4 in", "tlr3 and tlr4 in a", "and tlr4 in a myd88", "tlr4 in a myd88 independent", "in a myd88 independent manner", "myd88 independent manner yamamoto", "independent manner yamamoto m", "manner yamamoto m et", "yamamoto m et al. 2003a", "m et al. 2003a .", "et al. 2003a . trif", "al. 2003a . trif is", "2003a . trif is recruited", ". trif is recruited to", "trif is recruited to the", "is recruited to the ligand", "recruited to the ligand stimulated", "to the ligand stimulated tlr3", "the ligand stimulated tlr3 or", "ligand stimulated tlr3 or 4", "stimulated tlr3 or 4 complex", "tlr3 or 4 complex via", "or 4 complex via its", "4 complex via its tir", "complex via its tir domain.", "via its tir domain. tlr3", "its tir domain. tlr3 directly", "tir domain. tlr3 directly binds", "domain. tlr3 directly binds trif", "directly binds trif oshiumi", "binds trif oshiumi h", "trif oshiumi h et", "oshiumi h et al 2003", "h et al 2003 .", "et al 2003 . in", "al 2003 . in contrast", ". in contrast the", "in contrast the tlr4", "contrast the tlr4 mediated", "the tlr4 mediated signaling pathway", "tlr4 mediated signaling pathway requires", "mediated signaling pathway requires two", "signaling pathway requires two adapter", "pathway requires two adapter molecules", "two adapter molecules tram", "molecules tram trif", "tram trif related adapter", "trif related adapter molecule or", "related adapter molecule or ticam2", "molecule or ticam2 and", "or ticam2 and trif.", "ticam2 and trif. tram", "trif. tram ticam2 is", "tram ticam2 is thought", "ticam2 is thought to", "is thought to bridge the", "thought to bridge the activated", "to bridge the activated tlr4", "bridge the activated tlr4 complex", "the activated tlr4 complex and", "activated tlr4 complex and trif", "complex and trif yamamoto", "and trif yamamoto m", "trif yamamoto m et", "yamamoto m et al. 2003b", "et al. 2003b tanimura", "al. 2003b tanimura n", "2003b tanimura n et", "tanimura n et al. 2008", "et al. 2008 kagan", "al. 2008 kagan lc", "2008 kagan lc et", "kagan lc et al. 2008", "lc et al. 2008 .

trif", "et al. 2008 .

trif recruitment", "al. 2008 .

trif recruitment to", "2008 .

trif recruitment to the", ".

trif recruitment to the tlr", "recruitment to the tlr complex", "to the tlr complex stimulates", "the tlr complex stimulates distinct", "tlr complex stimulates distinct pathways", "complex stimulates distinct pathways leading", "stimulates distinct pathways leading to", "distinct pathways leading to the", "pathways leading to the production", "leading to the production of", "to the production of type", "the production of type i", "production of type i interferons", "type i interferons ifns", "interferons ifns and", "ifns and pro inflammatory", "and pro inflammatory cytokines and", "pro inflammatory cytokines and to", "inflammatory cytokines and to the", "cytokines and to the induction", "and to the induction of", "to the induction of programmed", "the induction of programmed cell", "induction of programmed cell death." ] }, { "record_id": "GLY_000594_1_87", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "166208", "r hsa", "hsa 166208", "r hsa 166208" ] }, { "record_id": "GLY_000594_1_87", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mtorc1 mediated", "mediated signalling", "mtorc1 mediated signalling", "mtorc1 integrates", "integrates four", "four major", "major signals", "signals \u2013", "\u2013 growth", "growth factors", "energy status", "oxygen and", "and amino", "amino acids", "acids \u2013", "\u2013 to", "to regulate", "regulate many", "many processes", "processes that", "that are", "are involved", "involved in", "in the", "the promotion", "promotion of", "of cell", "cell growth.", "growth. growth", "factors stimulate", "stimulate mtorc1", "mtorc1 through", "through the", "the activation", "activation of", "of the", "the canonical", "canonical insulin", "insulin and", "and ras", "ras signaling", "signaling pathways.", "pathways. the", "the energy", "status of", "the cell", "cell is", "is signaled", "signaled to", "to mtorc1", "through amp", "amp activated", "activated protein", "protein kinase", "a key", "key sensor", "sensor of", "of intracellular", "intracellular energy", "hardie 2007", "2007 .", ". energy", "energy depletion", "low atp:adp", "atp:adp ratio", "activates ampk", "ampk which", "which phosphorylates", "phosphorylates tsc2", "increasing its", "its gap", "gap activity", "activity towards", "towards rheb", "rheb which", "which reduces", "reduces mtorc1", "mtorc1 activation", "inoki et", "et al.", "al. 2003", "2003 .", ". ampk", "ampk can", "can reduce", "reduce mtorc1", "mtorc1 activity", "activity by", "by directly", "directly phosphorylating", "phosphorylating raptor", "gwinn et", "al. 2008", "2008 .", ". amino", "acids positively", "positively regulate", "regulate mtorc1", "reviewed by", "by guertin", "guertin &", "& sabatini", "sabatini 2007", ". in", "the presence", "presence of", "of amino", "rag proteins", "proteins bind", "bind raptor", "raptor to", "to promote", "promote the", "the relocalization", "relocalization of", "of mtorc1", "mtorc1 from", "from the", "the cytoplasm", "cytoplasm to", "to lysosomal", "lysosomal membranes", "puertollano 2014", "where it", "it is", "is activated", "activated by", "by rheb", "saucedo et", "stocker et", ". translocation", "translocation of", "of mtor", "mtor to", "to the", "the lysosome", "lysosome requires", "requires active", "active rag", "rag gtpases", "gtpases and", "and a", "a complex", "complex known", "known as", "as ragulator", "a pentameric", "pentameric protein", "protein complex", "complex that", "that anchors", "anchors the", "the rag", "gtpases to", "to lysosomes", "sancak et", "bar peled", "peled et", "al. 2012", "2012 .", ". rag", "proteins function", "function as", "as heterodimers", "consisting of", "of gtp", "gtp bound", "bound raga", "raga or", "or ragb", "ragb complexed", "complexed with", "with gdp", "gdp bound", "bound ragc", "ragc or", "or ragd.", "ragd. amino", "acids may", "may trigger", "trigger the", "the gtp", "gtp loading", "loading of", "of raga/b", "thereby promoting", "promoting binding", "binding to", "to raptor", "raptor and", "and assembly", "assembly of", "of an", "an activated", "activated mtorc1", "mtorc1 complex", "though a", "a recent", "recent study", "study suggested", "suggested that", "that the", "mtorc1 is", "is not", "not dependent", "dependent on", "on rag", "rag gtp", "gtp charging", "oshiro et", "al. 2014", "2014 .", ". the", "the activity", "activity of", "of rheb", "rheb is", "is regulated", "regulated by", "by a", "complex consisting", "of tuberous", "tuberous sclerosis", "sclerosis complex", "complex 1", "and tbc1", "tbc1 domain", "domain family", "family member", "member 7", "huang et", "dibble et", ". this", "this complex", "complex localizes", "localizes to", "lysosomes and", "and functions", "functions as", "as a", "a gtpase", "gtpase activating", "activating protein", "that inhibits", "inhibits the", "menon et", "demetriades et", "of growth", "factors or", "or insulin", "tsc 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signaling pathways.", "signaling pathways. the", "pathways. the energy", "the energy status", "energy status of", "status of the", "of the cell", "the cell is", "cell is signaled", "is signaled to", "signaled to mtorc1", "to mtorc1 through", "mtorc1 through amp", "through amp activated", "amp activated protein", "activated protein kinase", "kinase ampk", "a key sensor", "key sensor of", "sensor of intracellular", "of intracellular energy", "intracellular energy status", "status hardie", "hardie 2007 .", "2007 . energy", ". energy depletion", "depletion low", "low atp:adp ratio", "ratio activates", "activates ampk which", "ampk which phosphorylates", "which phosphorylates tsc2", "tsc2 increasing", "increasing its gap", "its gap activity", "gap activity towards", "activity towards rheb", "towards rheb which", "rheb which reduces", "which reduces mtorc1", "reduces mtorc1 activation", "activation inoki", "inoki et al.", "et al. 2003", "al. 2003 .", "2003 . ampk", ". ampk can", "ampk can reduce", "can reduce mtorc1", "reduce mtorc1 activity", "mtorc1 activity by", "activity by directly", "by directly phosphorylating", "directly phosphorylating raptor", "raptor gwinn", "gwinn et al.", "et al. 2008", "al. 2008 .", "2008 . amino", ". amino acids", "amino acids positively", "acids positively regulate", "positively regulate mtorc1", "mtorc1 reviewed", "reviewed by guertin", "by guertin &", "guertin & sabatini", "& sabatini 2007", "sabatini 2007 .", "2007 . in", ". in the", "in the presence", "the presence of", "presence of amino", "of amino acids", "acids rag", "rag proteins bind", "proteins bind raptor", "bind raptor to", "raptor to promote", "to promote the", "promote the relocalization", "the relocalization of", "relocalization of mtorc1", "of mtorc1 from", "mtorc1 from the", "from the cytoplasm", "the cytoplasm to", "cytoplasm to lysosomal", "to lysosomal membranes", "membranes puertollano", "2014 where", "where it is", "it is activated", "is activated by", "activated by rheb", "rheb saucedo", "saucedo et al.", "2003 stocker", "stocker et al.", "2003 . translocation", ". translocation of", "translocation of mtor", "of mtor to", "mtor to the", "to the lysosome", "the lysosome requires", "lysosome requires active", "requires active rag", "active rag gtpases", "rag gtpases and", "gtpases and a", "and a complex", "a complex known", "complex known as", "known as ragulator", "ragulator a", "a pentameric protein", "pentameric protein complex", "protein complex that", "complex that anchors", "that anchors the", "anchors the rag", "the rag gtpases", "rag gtpases to", "gtpases to lysosomes", "lysosomes sancak", "sancak et al.", "2008 2010", "2010 bar", "bar peled et", "peled et al.", "et al. 2012", "al. 2012 .", "2012 . rag", ". rag proteins", "rag proteins function", "proteins function as", "function as heterodimers", "heterodimers consisting", "consisting of gtp", "of gtp bound", "gtp bound raga", "bound raga or", "raga or ragb", "or ragb complexed", "ragb complexed with", "complexed with gdp", "with gdp bound", "gdp bound ragc", "bound ragc or", "ragc or ragd.", "or ragd. amino", "ragd. amino acids", "amino acids may", "acids may trigger", "may trigger the", "trigger the gtp", "the gtp loading", "gtp loading of", "loading of raga/b", "raga/b thereby", "thereby promoting binding", "promoting binding to", "binding to raptor", "to raptor and", "raptor and assembly", "and assembly of", "assembly of an", "of an activated", "an activated mtorc1", "activated mtorc1 complex", "complex though", "though a recent", "a recent study", "recent study suggested", "study suggested that", "suggested that the", "that the activation", "activation of mtorc1", "of mtorc1 is", "mtorc1 is not", "is not dependent", "not dependent on", "dependent on rag", "on rag gtp", "rag gtp charging", "charging oshiro", "oshiro et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the activity", "the activity of", "activity of rheb", "of rheb is", "rheb is regulated", "is regulated by", "regulated by a", "by a complex", "a complex consisting", "complex consisting of", "consisting of tuberous", "of tuberous sclerosis", "tuberous sclerosis complex", "sclerosis complex 1", "1 tsc1", "tsc2 and", "and tbc1 domain", "tbc1 domain family", "domain family member", "family member 7", "7 tbc1d7", "huang et al.", "2008 dibble", "dibble et al.", "2012 . this", ". this complex", "this complex localizes", "complex localizes to", "localizes to lysosomes", "to lysosomes and", "lysosomes and functions", "and functions as", "functions as a", "as a gtpase", "a gtpase activating", "gtpase activating protein", "protein gap", "gap that", "that inhibits the", "inhibits the activity", "rheb menon", "menon et al.", "2014 demetriades", "demetriades et al.", "2014 . in", "presence of growth", "of growth factors", "growth factors or", "factors or insulin", "insulin tsc", "tsc releases its", "releases its inhibitory", "its inhibitory activity", "inhibitory activity on", "activity on rheb", "rheb thus", "thus allowing the", "allowing the activation", "activation of mtorc1.", "mtorc1 integrates four major", "integrates four major signals", "four major signals \u2013", "major signals \u2013 growth", "signals \u2013 growth factors", "growth factors energy", "factors energy status", "energy status oxygen", "status oxygen and", "oxygen and amino acids", "and amino acids \u2013", "amino acids \u2013 to", "acids \u2013 to regulate", "\u2013 to regulate many", "to regulate many processes", "regulate many processes that", "many processes that are", "processes that are involved", "that are involved in", "are involved in the", "involved in the promotion", "in the promotion of", "the promotion of cell", "promotion of cell growth.", "of cell growth. growth", "cell growth. growth factors", "growth. growth factors stimulate", "growth factors stimulate mtorc1", "factors stimulate mtorc1 through", "stimulate mtorc1 through the", "mtorc1 through the activation", "through the activation of", "the activation of the", "activation of the canonical", "of the canonical insulin", "the canonical insulin and", "canonical insulin and ras", "insulin and ras signaling", "and ras signaling pathways.", "ras signaling pathways. the", "signaling pathways. the energy", "pathways. the energy status", "the energy status of", "energy status of the", "status of the cell", "of the cell is", "the cell is signaled", "cell is signaled to", "is signaled to mtorc1", "signaled to mtorc1 through", "to mtorc1 through amp", "mtorc1 through amp activated", "through amp activated protein", "amp activated protein kinase", "protein kinase ampk", "ampk a", "a key sensor of", "key sensor of intracellular", "sensor of intracellular energy", "of intracellular energy status", "energy status hardie", "status hardie 2007", "hardie 2007 . energy", "2007 . energy depletion", "energy depletion low", "depletion low atp:adp", "atp:adp ratio activates", "ratio activates ampk", "activates ampk which phosphorylates", "ampk which phosphorylates tsc2", "phosphorylates tsc2 increasing", "tsc2 increasing its", "increasing its gap activity", "its gap activity towards", "gap activity towards rheb", "activity towards rheb which", "towards rheb which reduces", "rheb which reduces mtorc1", "which reduces mtorc1 activation", "mtorc1 activation inoki", "activation inoki et", "inoki et al. 2003", "et al. 2003 .", "al. 2003 . ampk", "2003 . ampk can", ". ampk can reduce", "ampk can reduce mtorc1", "can reduce mtorc1 activity", "reduce mtorc1 activity by", "mtorc1 activity by directly", "activity by directly phosphorylating", "by directly phosphorylating raptor", "phosphorylating raptor gwinn", "raptor gwinn et", "gwinn et al. 2008", "et al. 2008 .", "al. 2008 . amino", "2008 . amino acids", ". amino acids positively", "amino acids positively regulate", "acids positively regulate mtorc1", "regulate mtorc1 reviewed", "mtorc1 reviewed by", "reviewed by guertin &", "by guertin & sabatini", "guertin & sabatini 2007", "& sabatini 2007 .", "sabatini 2007 . in", "2007 . in the", ". in the presence", "in the presence of", "the presence of amino", "presence of amino acids", "amino acids rag", "acids rag proteins", "rag proteins bind raptor", "proteins bind raptor to", "bind raptor to promote", "raptor to promote the", "to promote the relocalization", "promote the relocalization of", "the relocalization of mtorc1", "relocalization of mtorc1 from", "of mtorc1 from the", "mtorc1 from the cytoplasm", "from the cytoplasm to", "the cytoplasm to lysosomal", "cytoplasm to lysosomal membranes", "lysosomal membranes puertollano", "membranes puertollano 2014", "puertollano 2014 where", "2014 where it", "where it is activated", "it is activated by", "is activated by rheb", "by rheb saucedo", "rheb saucedo et", "saucedo et al. 2003", "al. 2003 stocker", "2003 stocker et", "stocker et al. 2003", "al. 2003 . translocation", "2003 . translocation of", ". translocation of mtor", "translocation of mtor to", "of mtor to the", "mtor to the lysosome", "to the lysosome requires", "the lysosome requires active", "lysosome requires active rag", "requires active rag gtpases", "active rag gtpases and", "rag gtpases and a", "gtpases and a complex", "and a complex known", "a complex known as", "complex known as ragulator", "as ragulator a", "ragulator a pentameric", "a pentameric protein complex", "pentameric protein complex that", "protein complex that anchors", "complex that anchors the", "that anchors the rag", "anchors the rag gtpases", "the rag gtpases to", "rag gtpases to lysosomes", "to lysosomes sancak", "lysosomes sancak et", "sancak et al. 2008", "al. 2008 2010", "2010 bar peled", "bar peled et al.", "peled et al. 2012", "et al. 2012 .", "al. 2012 . rag", "2012 . rag proteins", ". rag proteins function", "rag proteins function as", "proteins function as heterodimers", "as heterodimers consisting", "heterodimers consisting of", "consisting of gtp bound", "of gtp bound raga", "gtp bound raga or", "bound raga or ragb", "raga or ragb complexed", "or ragb complexed with", "ragb complexed with gdp", "complexed with gdp bound", "with gdp bound ragc", "gdp bound ragc or", "bound ragc or ragd.", "ragc or ragd. amino", "or ragd. amino acids", "ragd. amino acids may", "amino acids may trigger", "acids may trigger the", "may trigger the gtp", "trigger the gtp loading", "the gtp loading of", "gtp loading of raga/b", "of raga/b thereby", "raga/b thereby promoting", "thereby promoting binding to", "promoting binding to raptor", "binding to raptor and", "to raptor and assembly", "raptor and assembly of", "and assembly of an", "assembly of an activated", "of an activated mtorc1", "an activated mtorc1 complex", "mtorc1 complex though", "complex though a", "though a recent study", "a recent study suggested", "recent study suggested that", "study suggested that the", "suggested that the activation", "that the activation of", "the activation of mtorc1", "activation of mtorc1 is", "of mtorc1 is not", "mtorc1 is not dependent", "is not dependent on", "not dependent on rag", "dependent on rag gtp", "on rag gtp charging", "gtp charging oshiro", "charging oshiro et", "oshiro et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the activity", ". the activity of", "the activity of rheb", "activity of rheb is", "of rheb is regulated", "rheb is regulated by", "is regulated by a", "regulated by a complex", "by a complex consisting", "a complex consisting of", "complex consisting of tuberous", "consisting of tuberous sclerosis", "of tuberous sclerosis complex", "tuberous sclerosis complex 1", "complex 1 tsc1", "tsc1 tsc2", "tsc2 and tbc1", "and tbc1 domain family", "tbc1 domain family member", "domain family member 7", "member 7 tbc1d7", "tbc1d7 huang", "huang et al. 2008", "al. 2008 dibble", "2008 dibble et", "dibble et al. 2012", "al. 2012 . this", "2012 . this complex", ". this complex localizes", "this complex localizes to", "complex localizes to lysosomes", "localizes to lysosomes and", "to lysosomes and functions", "lysosomes and functions as", "and functions as a", "functions as a gtpase", "as a gtpase activating", "a gtpase activating protein", "activating protein gap", "gap that inhibits", "that inhibits the activity", "inhibits the activity of", "of rheb menon", "rheb menon et", "menon et al. 2014", "al. 2014 demetriades", "2014 demetriades et", "demetriades et al. 2014", "al. 2014 . in", "2014 . in the", "the presence of growth", "presence of growth factors", "of growth factors or", "growth factors or insulin", "or insulin tsc", "insulin tsc releases", "tsc releases its inhibitory", "releases its inhibitory activity", "its inhibitory activity on", "inhibitory activity on rheb", "on rheb thus", "rheb thus allowing", "thus allowing the activation", "allowing the activation of", "the activation of mtorc1.", "mtorc1 integrates four major signals", "integrates four major signals \u2013", "four major signals \u2013 growth", "major signals \u2013 growth factors", "\u2013 growth factors energy", "growth factors energy status", "energy status oxygen and", "status oxygen and amino", "oxygen and amino acids \u2013", "and amino acids \u2013 to", "amino acids \u2013 to regulate", "acids \u2013 to regulate many", "\u2013 to regulate many processes", "to regulate many processes that", "regulate many processes that are", "many processes that are involved", "processes that are involved in", "that are involved in the", "are involved in the promotion", "involved in the promotion of", "in the promotion of cell", "the promotion of cell growth.", "promotion of cell growth. growth", "of cell growth. growth factors", "cell growth. growth factors stimulate", "growth. growth factors stimulate mtorc1", "growth factors stimulate mtorc1 through", "factors stimulate mtorc1 through the", "stimulate mtorc1 through the activation", "mtorc1 through the activation of", "through the activation of the", "the activation of the canonical", "activation of the canonical insulin", "of the canonical insulin and", "the canonical insulin and ras", "canonical insulin and ras signaling", "insulin and ras signaling pathways.", "and ras signaling pathways. the", "ras signaling pathways. the energy", "signaling pathways. the energy status", "pathways. the energy status of", "the energy status of the", "energy status of the cell", "status of the cell is", "of the cell is signaled", "the cell is signaled to", "cell is signaled to mtorc1", "is signaled to mtorc1 through", "signaled to mtorc1 through amp", "to mtorc1 through amp activated", "mtorc1 through amp activated protein", "through amp activated protein kinase", "activated protein kinase ampk", "ampk a key", "a key sensor of intracellular", "key sensor of intracellular energy", "sensor of intracellular energy status", "intracellular energy status hardie", "energy status hardie 2007", "status hardie 2007 .", "hardie 2007 . energy depletion", ". energy depletion low", "energy depletion low atp:adp", "depletion low atp:adp ratio", "low atp:adp ratio activates", "atp:adp ratio activates ampk", "ratio activates ampk which", "activates ampk which phosphorylates tsc2", "which phosphorylates tsc2 increasing", "phosphorylates tsc2 increasing its", "tsc2 increasing its gap", "increasing its gap activity towards", "its gap activity towards rheb", "gap activity towards rheb which", "activity towards rheb which reduces", "towards rheb which reduces mtorc1", "rheb which reduces mtorc1 activation", "reduces mtorc1 activation inoki", "mtorc1 activation inoki et", "activation inoki et al.", "inoki et al. 2003 .", "et al. 2003 . ampk", "al. 2003 . ampk can", "2003 . ampk can reduce", ". ampk can reduce mtorc1", "ampk can reduce mtorc1 activity", "can reduce mtorc1 activity by", "reduce mtorc1 activity by directly", "mtorc1 activity by directly phosphorylating", "activity by directly phosphorylating raptor", "directly phosphorylating raptor gwinn", "phosphorylating raptor gwinn et", "raptor gwinn et al.", "gwinn et al. 2008 .", "et al. 2008 . amino", "al. 2008 . amino acids", "2008 . amino acids positively", ". amino acids positively regulate", "amino acids positively regulate mtorc1", "positively regulate mtorc1 reviewed", "regulate mtorc1 reviewed by", "mtorc1 reviewed by guertin", "reviewed by guertin & sabatini", "by guertin & sabatini 2007", "guertin & sabatini 2007 .", "& sabatini 2007 . in", "sabatini 2007 . in the", "2007 . in the presence", ". in the presence of", "in the presence of amino", "the presence of amino acids", "of amino acids rag", "amino acids rag proteins", "acids rag proteins bind", "rag proteins bind raptor to", "proteins bind raptor to promote", "bind raptor to promote the", "raptor to promote the relocalization", "to promote the relocalization of", "promote the relocalization of mtorc1", "the relocalization of mtorc1 from", "relocalization of mtorc1 from the", "of mtorc1 from the cytoplasm", "mtorc1 from the cytoplasm to", "from the cytoplasm to lysosomal", "the cytoplasm to lysosomal membranes", "to lysosomal membranes puertollano", "lysosomal membranes puertollano 2014", "puertollano 2014 where it", "2014 where it is", "where it is activated by", "it is activated by rheb", "activated by rheb saucedo", "by rheb saucedo et", "rheb saucedo et al.", "et al. 2003 stocker", "al. 2003 stocker et", "2003 stocker et al.", "stocker et al. 2003 .", "et al. 2003 . translocation", "al. 2003 . translocation of", "2003 . translocation of mtor", ". translocation of mtor to", "translocation of mtor to the", "of mtor to the lysosome", "mtor to the lysosome requires", "to the lysosome requires active", "the lysosome requires active rag", "lysosome requires active rag gtpases", "requires active rag gtpases and", "active rag gtpases and a", "rag gtpases and a complex", "gtpases and a complex known", "and a complex known as", "a complex known as ragulator", "known as ragulator a", "as ragulator a pentameric", "ragulator a pentameric protein", "a pentameric protein complex that", "pentameric protein complex that anchors", "protein complex that anchors the", "complex that anchors the rag", "that anchors the rag gtpases", "anchors the rag gtpases to", "the rag gtpases to lysosomes", "gtpases to lysosomes sancak", "to lysosomes sancak et", "lysosomes sancak et al.", "et al. 2008 2010", "2008 2010 bar", "2010 bar peled et", "bar peled et al. 2012", "peled et al. 2012 .", "et al. 2012 . rag", "al. 2012 . rag proteins", "2012 . rag proteins function", ". rag proteins function as", "rag proteins function as heterodimers", "function as heterodimers consisting", "as heterodimers consisting of", "heterodimers consisting of gtp", "consisting of gtp bound raga", "of gtp bound raga or", "gtp bound raga or ragb", "bound raga or ragb complexed", "raga or ragb complexed with", "or ragb complexed with gdp", "ragb complexed with gdp bound", "complexed with gdp bound ragc", "with gdp bound ragc or", "gdp bound ragc or ragd.", "bound ragc or ragd. amino", "ragc or ragd. amino acids", "or ragd. amino acids may", "ragd. amino acids may trigger", "amino acids may trigger the", "acids may trigger the gtp", "may trigger the gtp loading", "trigger the gtp loading of", "the gtp loading of raga/b", "loading of raga/b thereby", "of raga/b thereby promoting", "raga/b thereby promoting binding", "thereby promoting binding to raptor", "promoting binding to raptor and", "binding to raptor and assembly", "to raptor and assembly of", "raptor and assembly of an", "and assembly of an activated", "assembly of an activated mtorc1", "of an activated mtorc1 complex", "activated mtorc1 complex though", "mtorc1 complex though a", "complex though a recent", "though a recent study suggested", "a recent study suggested that", "recent study suggested that the", "study suggested that the activation", "suggested that the activation of", "that the activation of mtorc1", "the activation of mtorc1 is", "activation of mtorc1 is not", "of mtorc1 is not dependent", "mtorc1 is not dependent on", "is not dependent on rag", "not dependent on rag gtp", "dependent on rag gtp charging", "rag gtp charging oshiro", "gtp charging oshiro et", "charging oshiro et al.", "oshiro et al. 2014 .", "et al. 2014 . the", "al. 2014 . the activity", "2014 . the activity of", ". the activity of rheb", "the activity of rheb is", "activity of rheb is regulated", "of rheb is regulated by", "rheb is regulated by a", "is regulated by a complex", "regulated by a complex consisting", "by a complex consisting of", "a complex consisting of tuberous", "complex consisting of tuberous sclerosis", "consisting of tuberous sclerosis complex", "of tuberous sclerosis complex 1", "sclerosis complex 1 tsc1", "tsc2 and tbc1 domain", "and tbc1 domain family member", "tbc1 domain family member 7", "family member 7 tbc1d7", "tbc1d7 huang et", "et al. 2008 dibble", "al. 2008 dibble et", "2008 dibble et al.", "dibble et al. 2012 .", "et al. 2012 . this", "al. 2012 . this complex", "2012 . this complex localizes", ". this complex localizes to", "this complex localizes to lysosomes", "complex localizes to lysosomes and", "localizes to lysosomes and functions", "to lysosomes and functions as", "lysosomes and functions as a", "and functions as a gtpase", "functions as a gtpase activating", "as a gtpase activating protein", "gtpase activating protein gap", "protein gap that", "gap that inhibits the", "that inhibits the activity of", "inhibits the activity of rheb", "activity of rheb menon", "of rheb menon et", "rheb menon et al.", "et al. 2014 demetriades", "al. 2014 demetriades et", "2014 demetriades et al.", "demetriades et al. 2014 .", "et al. 2014 . in", "al. 2014 . in the", "2014 . in the presence", "in the presence of growth", "the presence of growth factors", "presence of growth factors or", "of growth factors or insulin", "factors or insulin tsc", "or insulin tsc releases", "insulin tsc releases its", "tsc releases its inhibitory activity", "releases its inhibitory activity on", "its inhibitory activity on rheb", "activity on rheb thus", "on rheb thus allowing", "rheb thus allowing the", "thus allowing the activation of", "allowing the activation of mtorc1." ] }, { "record_id": "GLY_000594_1_88", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "166662", "r hsa", "hsa 166662", "r hsa 166662" ] }, { "record_id": "GLY_000594_1_88", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lectin pathway", "pathway of", "of complement", "complement activation", "lectin pathway of", "pathway of complement", "of complement activation", "lectin pathway of complement", "pathway of complement activation", "lectin pathway of complement activation", "activation of", "of the", "the lectin", "is initiated", "initiated by", "by mannose", "mannose binding", "binding lectin", "the hetero", "hetero complex", "complex cl", "cl lk", "lk formed", "formed from", "from colec11", "collectin liver", "liver 1", "cl l1", "and colec10", "collectin kidney", "kidney 1", "cl k1", "and the", "the ficolins", "fcn3 .", ". all", "all are", "are ca", "ca dependent", "c type", "lectins that", "that initiate", "initiate the", "the complement", "complement cascade", "cascade after", "after binding", "binding to", "to specific", "specific carbohydrate", "carbohydrate patterns", "patterns on", "on the", "the target", "target cell", "cell surface.", "surface. all", "all form", "form trimers", "trimers and", "and larger", "larger oligomers", "jensen et", "et al.", "al. 2005", "dommett et", "al. 2006", "garlatti et", "al. 2010", "2010 .", ". mbl", "mbl and", "and ficolins", "ficolins circulate", "circulate in", "in plasma", "plasma as", "as complexes", "complexes with", "with homodimers", "homodimers of", "of mbl", "mbl associated", "associated serine", "serine proteases", "fujita et", "al. 2004", "hajela et", "al. 2002", "2002 .", ". masp1", "masp2 and", "and masp3", "masp3 have", "have all", "all been", "been reported", "reported to", "to mediate", "mediate complement", "complement activation.", "activation. upon", "upon binding", "binding of", "of human", "human lectin", "lectin to", "to the", "target surface", "the complex", "complex of", "of lectin:masp", "lectin:masp undergoes", "undergoes conformational", "conformational changes", "changes that", "that result", "result in", "in masp", "masp cleavage", "cleavage and", "and activation", "matsushita m", "m et", "al. 2000", "2004 .", ". active", "active masp2", "masp2 cleaves", "cleaves c4", "c4 to", "to generate", "generate c4a", "c4a and", "and c4b.", "c4b. c4b", "c4b binds", "binds to", "cell surface", "surface via", "via its", "its thioester", "thioester bond", "then binds", "binds circulating", "circulating c2", "law and", "and dodds", "dodds 1997", "1997 .", ". bound", "bound c2", "c2 is", "is cleaved", "cleaved by", "by masp2", "masp2 to", "to yield", "yield the", "the c3", "c3 convertase", "convertase c4b:c2a.", "c4b:c2a. the", "the active", "active form", "form of", "of masp1", "masp1 was", "was reported", "to cleave", "cleave c2", "c2 in", "in a", "a manner", "manner similar", "similar to", "to masp2", "matsushita et", "chen &", "& wallis", "wallis 2004", "masp1 can", "can cleave", "cleave proenzyme", "proenzyme masp2", "leading to", "to complement", "heja et", "al. 2012", "2012 .", "can also", "also cleave", "cleave fibrinogen", "fibrinogen to", "yield fibrinopeptide", "fibrinopeptide b", "and activates", "activates factor", "factor xiii.", "xiii. masp1", "masp1 may", "may have", "have a", "a role", "role in", "in removal", "removal of", "of 'dead", "'dead c3'", "i.e. c3", "c3 h2o", ". in", "in addition", "addition to", "to masp1", "masp1 to", "to 3", "two alternatively", "alternatively slpiced", "slpiced forms", "forms of", "and masp2", "have been", "been implicated", "implicated in", "in complement", "cascade signaling", "takahashi et", "al. 1999", "degn et", ". the", "the functions", "functions of", "of masp3", "smap and", "and map44", "map44 in", "in the", "pathway remain", "remain to", "to be", "be clarified.", "activation of the", "of the lectin", "the lectin pathway", "pathway lp", "lp is", "is initiated by", "initiated by mannose", "by mannose binding", "mannose binding lectin", "lectin mbl", "the hetero complex", "hetero complex cl", "complex cl lk", "cl lk formed", "lk formed from", "formed from colec11", "colec11 collectin", "collectin liver 1", "1 cl", "l1 and", "colec10 collectin", "collectin kidney 1", "and the ficolins", "ficolins fcn1", "fcn1 fcn2", "fcn2 fcn3", "fcn3 . all", ". all are", "all are ca", "are ca dependent", "dependent c", "type lectins", "lectins that initiate", "that initiate the", "initiate the complement", "the complement cascade", "complement cascade after", "cascade after binding", "after binding to", "binding to specific", "to specific carbohydrate", "specific carbohydrate patterns", "carbohydrate patterns on", "patterns on the", "on the target", "the target cell", "target cell surface.", "cell surface. all", "surface. all form", "all form trimers", "form trimers and", "trimers and larger", "and larger oligomers", "oligomers jensen", "jensen et al.", "et al. 2005", "2005 dommett", "dommett et al.", "et al. 2006", "2006 garlatti", "garlatti et al.", "et al. 2010", "al. 2010 .", "2010 . mbl", ". mbl and", "mbl and ficolins", "and ficolins circulate", "ficolins circulate in", "circulate in plasma", "in plasma as", "plasma as complexes", "as complexes with", "complexes with homodimers", "with homodimers of", "homodimers of mbl", "of mbl associated", "mbl associated serine", "associated serine proteases", "proteases masp", "fujita et al.", "et al. 2004", "2004 hajela", "hajela et al.", "et al. 2002", "al. 2002 .", "2002 . masp1", "masp1 masp2", "masp2 and masp3", "and masp3 have", "masp3 have all", "have all been", "all been reported", "been reported to", "reported to mediate", "to mediate complement", "mediate complement activation.", "complement activation. upon", "activation. upon binding", "upon binding of", "binding of human", "of human lectin", "human lectin to", "lectin to the", "to the target", "the target surface", "surface the", "the complex of", "complex of lectin:masp", "of lectin:masp undergoes", "lectin:masp undergoes conformational", "undergoes conformational changes", "conformational changes that", "changes that result", "that result in", "result in masp", "in masp cleavage", "masp cleavage and", "cleavage and activation", "activation matsushita", "matsushita m et", "m et al.", "et al. 2000", "2000 fujita", "al. 2004 .", "2004 . active", ". active masp2", "active masp2 cleaves", "masp2 cleaves c4", "cleaves c4 to", "c4 to generate", "to generate c4a", "generate c4a and", "c4a and c4b.", "and c4b. c4b", "c4b. c4b binds", "c4b binds to", "binds to the", "target cell surface", "cell surface via", "surface via its", "via its thioester", "its thioester bond", "bond then", "then binds circulating", "binds circulating c2", "c2 law", "law and dodds", "and dodds 1997", "dodds 1997 .", "1997 . bound", ". bound c2", "bound c2 is", "c2 is cleaved", "is cleaved by", "cleaved by masp2", "by masp2 to", "masp2 to yield", "to yield the", "yield the c3", "the c3 convertase", "c3 convertase c4b:c2a.", "convertase c4b:c2a. the", "c4b:c2a. the active", "the active form", "active form of", "form of masp1", "of masp1 was", "masp1 was reported", "was reported to", "reported to cleave", "to cleave c2", "cleave c2 in", "c2 in a", "in a manner", "a manner similar", "manner similar to", "similar to masp2", "masp2 matsushita", "matsushita et al.", "2000 chen", "chen & wallis", "& wallis 2004", "wallis 2004 .", "2004 . masp1", ". masp1 can", "masp1 can cleave", "can cleave proenzyme", "cleave proenzyme masp2", "masp2 leading", "leading to complement", "to complement activation", "activation heja", "heja et al.", "et al. 2012", "al. 2012 .", "2012 . masp1", "masp1 can also", "can also cleave", "also cleave fibrinogen", "cleave fibrinogen to", "fibrinogen to yield", "to yield fibrinopeptide", "yield fibrinopeptide b", "b and", "and activates factor", "activates factor xiii.", "factor xiii. masp1", "xiii. masp1 may", "masp1 may have", "may have a", "have a role", "a role in", "role in removal", "in removal of", "removal of 'dead", "of 'dead c3'", "c3' i.e.", "i.e. c3 h2o", "2002 . in", ". in addition", "in addition to", "addition to masp1", "to masp1 to", "masp1 to 3", "3 two", "two alternatively slpiced", "alternatively slpiced forms", "slpiced forms of", "forms of masp1", "masp1 map44", "map44 and", "masp2 smap", "smap have", "have been implicated", "been implicated in", "implicated in complement", "in complement cascade", "complement cascade signaling", "signaling takahashi", "takahashi et al.", "et al. 1999", "1999 degn", "degn et al.", "2010 . the", ". the functions", "the functions of", "functions of masp3", "masp3 smap", "smap and map44", "and map44 in", "map44 in the", "in the lectin", "lectin pathway remain", "pathway remain to", "remain to be", "to be clarified.", "activation of the lectin", "of the lectin pathway", "lectin pathway lp", "lp is initiated", "is initiated by mannose", "initiated by mannose binding", "by mannose binding lectin", "binding lectin mbl", "mbl the", "the hetero complex cl", "hetero complex cl lk", "complex cl lk formed", "cl lk formed from", "lk formed from colec11", "from colec11 collectin", "colec11 collectin liver", "liver 1 cl", "1 cl l1", "cl l1 and", "l1 and colec10", "and colec10 collectin", "colec10 collectin kidney", "kidney 1 cl", "1 cl k1", "k1 and", "the ficolins fcn1", "fcn2 fcn3 .", "fcn3 . all are", ". all are ca", "all are ca dependent", "ca dependent c", "dependent c type", "c type lectins", "type lectins that", "lectins that initiate the", "that initiate the complement", "initiate the complement cascade", "the complement cascade after", "complement cascade after binding", "cascade after binding to", "after binding to specific", "binding to specific carbohydrate", "to specific carbohydrate patterns", "specific carbohydrate patterns on", "carbohydrate patterns on the", "patterns on the target", "on the target cell", "the target cell surface.", "target cell surface. all", "cell surface. all form", "surface. all form trimers", "all form trimers and", "form trimers and larger", "trimers and larger oligomers", "larger oligomers jensen", "oligomers jensen et", "jensen et al. 2005", "al. 2005 dommett", "2005 dommett et", "dommett et al. 2006", "al. 2006 garlatti", "2006 garlatti et", "garlatti et al. 2010", "et al. 2010 .", "al. 2010 . mbl", "2010 . mbl and", ". mbl and ficolins", "mbl and ficolins circulate", "and ficolins circulate in", "ficolins circulate in plasma", "circulate in plasma as", "in plasma as complexes", "plasma as complexes with", "as complexes with homodimers", "complexes with homodimers of", "with homodimers of mbl", "homodimers of mbl associated", "of mbl associated serine", "mbl associated serine proteases", "serine proteases masp", "masp fujita", "fujita et al. 2004", "al. 2004 hajela", "2004 hajela et", "hajela et al. 2002", "et al. 2002 .", "al. 2002 . masp1", ". masp1 masp2", "masp1 masp2 and", "masp2 and masp3 have", "and masp3 have all", "masp3 have all been", "have all been reported", "all been reported to", "been reported to mediate", "reported to mediate complement", "to mediate complement activation.", "mediate complement activation. upon", "complement activation. upon binding", "activation. upon binding of", "upon binding of human", "binding of human lectin", "of human lectin to", "human lectin to the", "lectin to the target", "to the target surface", "target surface the", "surface the complex", "the complex of lectin:masp", "complex of lectin:masp undergoes", "of lectin:masp undergoes conformational", "lectin:masp undergoes conformational changes", "undergoes conformational changes that", "conformational changes that result", "changes that result in", "that result in masp", "result in masp cleavage", "in masp cleavage and", "masp cleavage and activation", "and activation matsushita", "activation matsushita m", "matsushita m et al.", "m et al. 2000", "al. 2000 fujita", "2000 fujita et", "et al. 2004 .", "al. 2004 . active", "2004 . active masp2", ". active masp2 cleaves", "active masp2 cleaves c4", "masp2 cleaves c4 to", "cleaves c4 to generate", "c4 to generate c4a", "to generate c4a and", "generate c4a and c4b.", "c4a and c4b. c4b", "and c4b. c4b binds", "c4b. c4b binds to", "c4b binds to the", "binds to the target", "to the target cell", "the target cell surface", "target cell surface via", "cell surface via its", "surface via its thioester", "via its thioester bond", "thioester bond then", "bond then binds", "then binds circulating c2", "circulating c2 law", "c2 law and", "law and dodds 1997", "and dodds 1997 .", "dodds 1997 . bound", "1997 . bound c2", ". bound c2 is", "bound c2 is cleaved", "c2 is cleaved by", "is cleaved by masp2", "cleaved by masp2 to", "by masp2 to yield", "masp2 to yield the", "to yield the c3", "yield the c3 convertase", "the c3 convertase c4b:c2a.", "c3 convertase c4b:c2a. the", "convertase c4b:c2a. the active", "c4b:c2a. the active form", "the active form of", "active form of masp1", "form of masp1 was", "of masp1 was reported", "masp1 was reported to", "was reported to cleave", "reported to cleave c2", "to cleave c2 in", "cleave c2 in a", "c2 in a manner", "in a manner similar", "a manner similar to", "manner similar to masp2", "to masp2 matsushita", "masp2 matsushita et", "matsushita et al. 2000", "al. 2000 chen", "2000 chen &", "chen & wallis 2004", "& wallis 2004 .", "wallis 2004 . masp1", "2004 . masp1 can", ". masp1 can cleave", "masp1 can cleave proenzyme", "can cleave proenzyme masp2", "proenzyme masp2 leading", "masp2 leading to", "leading to complement activation", "complement activation heja", "activation heja et", "heja et al. 2012", "et al. 2012 .", "al. 2012 . masp1", "2012 . masp1 can", ". masp1 can also", "masp1 can also cleave", "can also cleave fibrinogen", "also cleave fibrinogen to", "cleave fibrinogen to yield", "fibrinogen to yield fibrinopeptide", "to yield fibrinopeptide b", "fibrinopeptide b and", "b and activates", "and activates factor xiii.", "activates factor xiii. masp1", "factor xiii. masp1 may", "xiii. masp1 may have", "masp1 may have a", "may have a role", "have a role in", "a role in removal", "role in removal of", "in removal of 'dead", "removal of 'dead c3'", "'dead c3' i.e.", "c3' i.e. c3", "h2o hajela", "al. 2002 . in", "2002 . in addition", ". in addition to", "in addition to masp1", "addition to masp1 to", "to masp1 to 3", "to 3 two", "3 two alternatively", "two alternatively slpiced forms", "alternatively slpiced forms of", "slpiced forms of masp1", "of masp1 map44", "map44 and masp2", "and masp2 smap", "smap have been", "have been implicated in", "been implicated in complement", "implicated in complement cascade", "in complement cascade signaling", "cascade signaling takahashi", "signaling takahashi et", "takahashi et al. 1999", "al. 1999 degn", "1999 degn et", "degn et al. 2010", "al. 2010 . the", "2010 . the functions", ". the functions of", "the functions of masp3", "of masp3 smap", "masp3 smap and", "smap and map44 in", "and map44 in the", "map44 in the lectin", "in the lectin pathway", "the lectin pathway remain", "lectin pathway remain to", "pathway remain to be", "remain to be clarified.", "activation of the lectin pathway", "the lectin pathway lp", "pathway lp is", "lp is initiated by", "is initiated by mannose binding", "initiated by mannose binding lectin", "mannose binding lectin mbl", "mbl the hetero", "the hetero complex cl lk", "hetero complex cl lk formed", "complex cl lk formed from", "cl lk formed from colec11", "formed from colec11 collectin", "from colec11 collectin liver", "colec11 collectin liver 1", "collectin liver 1 cl", "liver 1 cl l1", "cl l1 and colec10", "and colec10 collectin kidney", "colec10 collectin kidney 1", "collectin kidney 1 cl", "kidney 1 cl k1", "cl k1 and", "k1 and the", "and the ficolins fcn1", "ficolins fcn1 fcn2", "fcn1 fcn2 fcn3", "fcn2 fcn3 . all", "fcn3 . all are ca", ". all are ca dependent", "are ca dependent c", "ca dependent c type", "c type lectins that", "type lectins that initiate", "lectins that initiate the complement", "that initiate the complement cascade", "initiate the complement cascade after", "the complement cascade after binding", "complement cascade after binding to", "cascade after binding to specific", "after binding to specific carbohydrate", "binding to specific carbohydrate patterns", "to specific carbohydrate patterns on", "specific carbohydrate patterns on the", "carbohydrate patterns on the target", "patterns on the target cell", "on the target cell surface.", "the target cell surface. all", "target cell surface. all form", "cell surface. all form trimers", "surface. all form trimers and", "all form trimers and larger", "form trimers and larger oligomers", "and larger oligomers jensen", "larger oligomers jensen et", "oligomers jensen et al.", "et al. 2005 dommett", "al. 2005 dommett et", "2005 dommett et al.", "et al. 2006 garlatti", "al. 2006 garlatti et", "2006 garlatti et al.", "garlatti et al. 2010 .", "et al. 2010 . mbl", "al. 2010 . mbl and", "2010 . mbl and ficolins", ". mbl and ficolins circulate", "mbl and ficolins circulate in", "and ficolins circulate in plasma", "ficolins circulate in plasma as", "circulate in plasma as complexes", "in plasma as complexes with", "plasma as complexes with homodimers", "as complexes with homodimers of", "complexes with homodimers of mbl", "with homodimers of mbl associated", "homodimers of mbl associated serine", "of mbl associated serine proteases", "associated serine proteases masp", "masp fujita et", "et al. 2004 hajela", "al. 2004 hajela et", "2004 hajela et al.", "hajela et al. 2002 .", "et al. 2002 . masp1", "2002 . masp1 masp2", ". masp1 masp2 and", "masp1 masp2 and masp3", "masp2 and masp3 have all", "and masp3 have all been", "masp3 have all been reported", "have all been reported to", "all been reported to mediate", "been reported to mediate complement", "reported to mediate complement activation.", "to mediate complement activation. upon", "mediate complement activation. upon binding", "complement activation. upon binding of", "activation. upon binding of human", "upon binding of human lectin", "binding of human lectin to", "of human lectin to the", "human lectin to the target", "lectin to the target surface", "the target surface the", "target surface the complex", "surface the complex of", "the complex of lectin:masp undergoes", "complex of lectin:masp undergoes conformational", "of lectin:masp undergoes conformational changes", "lectin:masp undergoes conformational changes that", "undergoes conformational changes that result", "conformational changes that result in", "changes that result in masp", "that result in masp cleavage", "result in masp cleavage and", "in masp cleavage and activation", "cleavage and activation matsushita", "and activation matsushita m", "activation matsushita m et", "matsushita m et al. 2000", "et al. 2000 fujita", "al. 2000 fujita et", "2000 fujita et al.", "fujita et al. 2004 .", "et al. 2004 . active", "al. 2004 . active masp2", "2004 . active masp2 cleaves", ". active masp2 cleaves c4", "active masp2 cleaves c4 to", "masp2 cleaves c4 to generate", "cleaves c4 to generate c4a", "c4 to generate c4a and", "to generate c4a and c4b.", "generate c4a and c4b. c4b", "c4a and c4b. c4b binds", "and c4b. c4b binds to", "c4b. c4b binds to the", "c4b binds to the target", "binds to the target cell", "to the target cell surface", "the target cell surface via", "target cell surface via its", "cell surface via its thioester", "surface via its thioester bond", "its thioester bond then", "thioester bond then binds", "bond then binds circulating", "binds circulating c2 law", "circulating c2 law and", "c2 law and dodds", "law and dodds 1997 .", "and dodds 1997 . bound", "dodds 1997 . bound c2", "1997 . bound c2 is", ". bound c2 is cleaved", "bound c2 is cleaved by", "c2 is cleaved by masp2", "is cleaved by masp2 to", "cleaved by masp2 to yield", "by masp2 to yield the", "masp2 to yield the c3", "to yield the c3 convertase", "yield the c3 convertase c4b:c2a.", "the c3 convertase c4b:c2a. the", "c3 convertase c4b:c2a. the active", "convertase c4b:c2a. the active form", "c4b:c2a. the active form of", "the active form of masp1", "active form of masp1 was", "form of masp1 was reported", "of masp1 was reported to", "masp1 was reported to cleave", "was reported to cleave c2", "reported to cleave c2 in", "to cleave c2 in a", "cleave c2 in a manner", "c2 in a manner similar", "in a manner similar to", "a manner similar to masp2", "similar to masp2 matsushita", "to masp2 matsushita et", "masp2 matsushita et al.", "et al. 2000 chen", "al. 2000 chen &", "2000 chen & wallis", "chen & wallis 2004 .", "& wallis 2004 . masp1", "wallis 2004 . masp1 can", "2004 . masp1 can cleave", ". masp1 can cleave proenzyme", "masp1 can cleave proenzyme masp2", "cleave proenzyme masp2 leading", "proenzyme masp2 leading to", "masp2 leading to complement", "to complement activation heja", "complement activation heja et", "activation heja et al.", "heja et al. 2012 .", "et al. 2012 . masp1", "al. 2012 . masp1 can", "2012 . masp1 can also", ". masp1 can also cleave", "masp1 can also cleave fibrinogen", "can also cleave fibrinogen to", "also cleave fibrinogen to yield", "cleave fibrinogen to yield fibrinopeptide", "fibrinogen to yield fibrinopeptide b", "yield fibrinopeptide b and", "fibrinopeptide b and activates", "b and activates factor", "and activates factor xiii. masp1", "activates factor xiii. masp1 may", "factor xiii. masp1 may have", "xiii. masp1 may have a", "masp1 may have a role", "may have a role in", "have a role in removal", "a role in removal of", "role in removal of 'dead", "in removal of 'dead c3'", "of 'dead c3' i.e.", "'dead c3' i.e. c3", "c3' i.e. c3 h2o", "c3 h2o hajela", "h2o hajela et", "et al. 2002 . in", "al. 2002 . in addition", "2002 . in addition to", ". in addition to masp1", "in addition to masp1 to", "addition to masp1 to 3", "masp1 to 3 two", "to 3 two alternatively", "3 two alternatively slpiced", "two alternatively slpiced forms of", "alternatively slpiced forms of masp1", "forms of masp1 map44", "masp1 map44 and", "masp2 smap have", "smap have been implicated", "have been implicated in complement", "been implicated in complement cascade", "implicated in complement cascade signaling", "complement cascade signaling takahashi", "cascade signaling takahashi et", "signaling takahashi et al.", "et al. 1999 degn", "al. 1999 degn et", "1999 degn et al.", "degn et al. 2010 .", "et al. 2010 . the", "al. 2010 . the functions", "2010 . the functions of", ". the functions of masp3", "functions of masp3 smap", "of masp3 smap and", "masp3 smap and map44", "smap and map44 in the", "and map44 in the lectin", "map44 in the lectin pathway", "in the lectin pathway remain", "the lectin pathway remain to", "lectin pathway remain to be", "pathway remain to be clarified." ] }, { "record_id": "GLY_000594_1_89", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "166663", "r hsa", "hsa 166663", "r hsa 166663" ] }, { "record_id": "GLY_000594_1_89", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "initial triggering", "triggering of", "of complement", "initial triggering of", "triggering of complement", "initial triggering of complement", "complement activation", "activation is", "is due", "due to", "to a", "a cascade", "cascade of", "of proteolytic", "proteolytic steps", "performed by", "by serine", "serine protease", "protease domains", 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ctd", "serine 5 phosphorylated ctd stimulates", "5 phosphorylated ctd stimulates guanylyltransferase", "phosphorylated ctd stimulates guanylyltransferase activity", "ctd stimulates guanylyltransferase activity in", "stimulates guanylyltransferase activity in vitro." ] }, { "record_id": "GLY_000594_1_93", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "167161", "r hsa", "hsa 167161", "r hsa 167161" ] }, { "record_id": "GLY_000594_1_93", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hiv transcription", "transcription initiation", "hiv transcription initiation", "formation of", "of the", "the open", "complex exposes", "exposes the", "the template", "template strand", "strand to", "to the", "the catalytic", "catalytic center", "center of", "the rna", "rna polymerase", "polymerase ii", "ii enzyme.", "enzyme. this", "this facilitates", "facilitates formation", "the first", "first phosphodiester", 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complex", "not involve open complex formation.", "open complex formation. this", "complex formation. this reaction", "this reaction is sensitive to", "reaction is sensitive to inhibition", "is sensitive to inhibition by", "sensitive to inhibition by single", "to inhibition by single stranded", "inhibition by single stranded oligonucleotides." ] }, { "record_id": "GLY_000594_1_94", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "167162", "r hsa", "hsa 167162", "r hsa 167162" ] }, { "record_id": "GLY_000594_1_94", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase ii", "ii hiv", "hiv promoter", "promoter escape", "rna polymerase ii", "polymerase ii hiv", "ii hiv promoter", "hiv promoter escape", "rna polymerase ii hiv", "polymerase ii hiv promoter", "ii hiv promoter escape", "rna polymerase ii hiv promoter", "polymerase ii hiv promoter escape", "ii promoter", "escape 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first phosphodiester bond has", "first phosphodiester bond has been", "phosphodiester bond has been created." ] }, { "record_id": "GLY_000594_1_95", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "167172", "r hsa", "hsa 167172", "r hsa 167172" ] }, { "record_id": "GLY_000594_1_95", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcription of", "of the", "the hiv", "hiv genome", "transcription of the", "of the hiv", "the hiv genome", "transcription of the hiv", "of the hiv genome", "transcription of the hiv genome", "expression of", "the integrated", "integrated hiv", "hiv 1", "1 provirus", "provirus is", "is dependent", "dependent on", "on the", "the host", "host cell", "cell pol", "pol ii", "ii transcription", "transcription machinery", "but is", "is regulated", "regulated in", "in critical", "critical ways", "ways by", "by hiv", "1 tat", "tat and", "and rev", "rev proteins.", "proteins. the", "the long", "long terminal", "terminal repeats", "located at", "at either", "either end", "end of", "the proviral", "proviral dna", "dna contain", "contain regulatory", "regulatory sequences", "sequences that", "that recruit", "recruit cellular", "cellular transcription", "transcription factors.", "factors. the", "the u3", "u3 region", "region of", "the 5'", "5' ltr", "ltr contains", "contains numerous", "numerous cis", "cis acting", "acting elements", "elements that", "that regulate", "regulate pol", "ii mediated", "mediated transcription", "transcription initiation.", "initiation. the", "the full", "full length", "length transcript", "which encodes", "encodes nine", "nine genes", "functions as", "as an", "an mrna", "mrna and", "and is", "is packaged", "packaged as", "as genomic", "genomic rna.", "viral mrnas", "mrnas are", "are generated", "generated by", "by alternative", "alternative splicing.", "splicing. the", "the activities", "activities of", "of tat", "rev create", 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cellular kinase", "the cellular kinase complex", "cellular kinase complex p", "kinase complex p tefb", "complex p tefb cyclin", "p tefb cyclin t1:cdk9", "cyclin t1:cdk9 and", "t1:cdk9 and recruits", "and recruits it to", "recruits it to the", "it to the tar", "to the tar stem", "the tar stem loop", "tar stem loop structure", "loop structure herrmann", "1995 wei", "wei et al. 1998", "et al. 1998 .", "al. 1998 . this", "1998 . this association", ". this association between", "this association between tat", "between tat tar", "tat tar and", "tar and p", "and p tefb", "cyclin t1:cdk9 is", "t1:cdk9 is believed", "is believed to bring", "believed to bring the", "to bring the catalytic", "bring the catalytic subunit", "the catalytic subunit of", "catalytic subunit of this", "subunit of this kinase", "of this kinase complex", "kinase complex cdk9", "cdk9 in close", "in close proximity to", "close proximity to pol", "proximity to pol ii", "to pol ii where", "pol ii where it", "ii where it hyperphosphorylates", "where it hyperphosphorylates the", "it hyperphosphorylates the ctd", "hyperphosphorylates the ctd of", "the ctd of rna", "ctd of rna pol", "pol ii zhou", "ii zhou et", "zhou et al. 2000", "et al. 2000 .", "al. 2000 . the", "2000 . the rd", ". the rd subunits", "the rd subunits of", "rd subunits of nelf", "subunits of nelf and", "of nelf and the", "nelf and the spt5", "and the spt5 subunit", "the spt5 subunit of", "spt5 subunit of dsif", "of dsif which", "dsif which associate", "which associate through rd", "associate through rd with", "through rd with the", "rd with the bottom", "with the bottom stem", "the bottom stem of", "bottom stem of tar", "of tar are", "tar are also", "are also phosphorylated by", "also phosphorylated by p", "phosphorylated by p tefb", "by p tefb cyclin", "yamaguchi et al. 2002", "al. 2002 fujinaga", "al. 2004 ivanov", "2004 ivanov et", "ivanov et al. 2000", "al. 2000 . phosphorylation", "2000 . phosphorylation of", ". phosphorylation of rd", "phosphorylation of rd results", "of rd results in", "rd results in its", "results in its dissociation", "in its dissociation from", "its dissociation from tar.", "dissociation from tar. thus", "tar. thus tat", "thus tat appears", "tat appears to facilitate", "appears to facilitate transcriptional", "to facilitate transcriptional elongation", "facilitate transcriptional elongation of", "transcriptional elongation of the", "hiv 1 transcript by", "1 transcript by hyperphosphorylating", "transcript by hyperphosphorylating the", "by hyperphosphorylating the rna", "hyperphosphorylating the rna poll", "the rna poll ii", "rna poll ii ctd", "poll ii ctd and", "ii ctd and by", "ctd and by removing", "and by removing the", "by removing the negative", "removing the negative transcription", "the negative transcription elongation", "negative transcription elongation factors", "transcription elongation factors from", "elongation factors from tar.", "from tar. in", "tar. in addition", "in addition there", "addition there is", "there is evidence that", "is evidence that the", "evidence that the association", "that the association of", "the association of tat", "association of tat with", "of tat with p", "tat with p tefb", "with p tefb cyclin", "cyclin t1:cdk9 alters", "t1:cdk9 alters the", "alters the substrate specificity", "the substrate specificity of", "substrate specificity of p", "specificity of p tefb", "of p tefb enhancing", "p tefb enhancing phosphorylation", "tefb enhancing phosphorylation of", "enhancing phosphorylation of ser5", "phosphorylation of ser5 residues", "of ser5 residues in", "ser5 residues in the", "residues in the ctd", "in the ctd of", "the tat protein is a", "tat protein is a viral", "protein is a viral transactivator", "is a viral transactivator protein", "a viral transactivator protein that", "viral transactivator protein that regulates", "transactivator protein that regulates hiv", "protein that regulates hiv 1", "that regulates hiv 1 gene", "regulates hiv 1 gene expression", "hiv 1 gene expression by", "1 gene expression by controlling", "gene expression by controlling rna", "expression by controlling rna pol", "by controlling rna pol ii", "controlling rna pol ii mediated", "rna pol ii mediated elongation", "ii mediated elongation reviewed", "mediated elongation reviewed in", "elongation reviewed in karn", "reviewed in karn 1999", "karn 1999 taube", "1999 taube et al.", "et al. 1999 liou", "al. 1999 liou et", "1999 liou et al.", "et al. 2004 barboric", "al. 2004 barboric and", "2004 barboric and peterlin", "barboric and peterlin 2005 .", "peterlin 2005 . tat", "2005 . tat appears", ". tat appears to", "tat appears to be required", "appears to be required in", "to be required in order", "be required in order to", "required in order to overcome", "in order to overcome the", "order to overcome the arrest", "to overcome the arrest of", "overcome the arrest of rna", "the arrest of rna pol", "arrest of rna pol ii", "of rna pol ii by", "rna pol ii by the", "pol ii by the negative", "ii by the negative transcriptional", "by the negative transcriptional elongation", "the negative transcriptional elongation factors", "negative transcriptional elongation factors dsif", "transcriptional elongation factors dsif and", "elongation factors dsif and nelf", "dsif and nelf wada", "and nelf wada et", "nelf wada et al.", "et al. 1998 yamaguchi", "al. 1998 yamaguchi et", "1998 yamaguchi et al.", "et al. 1999 yamaguchi", "al. 1999 yamaguchi et", "1999 yamaguchi et al", "et al 2002 fujinaga", "al 2002 fujinaga et", "2002 fujinaga et al.", "fujinaga et al. 2004 .", "et al. 2004 . while", "al. 2004 . while pol", "2004 . while pol ii", ". while pol ii can", "while pol ii can associate", "pol ii can associate with", "ii can associate with the", "can associate with the proviral", "associate with the proviral ltr", "with the proviral ltr and", "the proviral ltr and initiate", "proviral ltr and initiate transcription", "ltr and initiate transcription in", "and initiate transcription in the", "initiate transcription in the absence", "transcription in the absence of", "in the absence of tat", "absence of tat these", "of tat these polymerase", "tat these polymerase complexes", "these polymerase complexes are non", "polymerase complexes are non processive", "complexes are non processive and", "are non processive and dissociate", "non processive and dissociate from", "processive and dissociate from the", "and dissociate from the template", "dissociate from the template prematurely", "from the template prematurely producing", "the template prematurely producing very", "template prematurely producing very short", "prematurely producing very short transcripts", "very short transcripts kao", "short transcripts kao et", "transcripts kao et al.", "kao et al. 1987 .", "et al. 1987 . tat", "al. 1987 . tat associates", "1987 . tat associates with", ". tat associates with the", "tat associates with the rna", "associates with the rna element", "the rna element tar", "element tar which", "tar which forms a", "which forms a stem loop", "forms a stem loop structure", "a stem loop structure in", "stem loop structure in the", "loop structure in the leader", "structure in the leader rna", "in the leader rna sequence", "leader rna sequence dingwall", "rna sequence dingwall et", "sequence dingwall et al.", "dingwall et al. 1989 .", "et al. 1989 . tat", "al. 1989 . tat also", "1989 . tat also associates", ". tat also associates with", "tat also associates with the", "also associates with the cellular", "associates with the cellular kinase", "with the cellular kinase complex", "the cellular kinase complex p", "cellular kinase complex p tefb", "kinase complex p tefb cyclin", "complex p tefb cyclin t1:cdk9", "tefb cyclin t1:cdk9 and", "cyclin t1:cdk9 and recruits", "t1:cdk9 and recruits it", "and recruits it to the", "recruits it to the tar", "it to the tar stem", "to the tar stem loop", "the tar stem loop structure", "stem loop structure herrmann", "structure herrmann 1995", "1995 wei et", "wei et al. 1998 .", "et al. 1998 . this", "al. 1998 . this association", "1998 . this association between", ". this association between tat", "association between tat tar", "between tat tar and", "tar and p tefb", "and p tefb cyclin", "tefb cyclin t1:cdk9 is", "cyclin t1:cdk9 is believed", "t1:cdk9 is believed to", "is believed to bring the", "believed to bring the catalytic", "to bring the catalytic subunit", "bring the catalytic subunit of", "the catalytic subunit of this", "catalytic subunit of this kinase", "subunit of this kinase complex", "this kinase complex cdk9", "complex cdk9 in", "cdk9 in close proximity", "in close proximity to pol", "close proximity to pol ii", "proximity to pol ii where", "to pol ii where it", "pol ii where it hyperphosphorylates", "ii where it hyperphosphorylates the", "where it hyperphosphorylates the ctd", "it hyperphosphorylates the ctd of", "hyperphosphorylates the ctd of rna", "the ctd of rna pol", "ctd of rna pol ii", "rna pol ii zhou", "pol ii zhou et", "ii zhou et al.", "zhou et al. 2000 .", "et al. 2000 . the", "al. 2000 . the rd", "2000 . the rd subunits", ". the rd subunits of", "the rd subunits of nelf", "rd subunits of nelf and", "subunits of nelf and the", "of nelf and the spt5", "nelf and the spt5 subunit", "and the spt5 subunit of", "the spt5 subunit of dsif", "subunit of dsif which", "of dsif which associate", "dsif which associate through", "which associate through rd with", "associate through rd with the", "through rd with the bottom", "rd with the bottom stem", "with the bottom stem of", "the bottom stem of tar", "stem of tar are", "of tar are also", "tar are also phosphorylated", "are also phosphorylated by p", "also phosphorylated by p tefb", "phosphorylated by p tefb cyclin", "by p tefb cyclin t1:cdk9", "t1:cdk9 yamaguchi", "et al. 2002 fujinaga", "al. 2002 fujinaga et", "et al. 2004 ivanov", "al. 2004 ivanov et", "2004 ivanov et al.", "ivanov et al. 2000 .", "et al. 2000 . phosphorylation", "al. 2000 . phosphorylation of", "2000 . phosphorylation of rd", ". phosphorylation of rd results", "phosphorylation of rd results in", "of rd results in its", "rd results in its dissociation", "results in its dissociation from", "in its dissociation from tar.", "its dissociation from tar. thus", "from tar. thus tat", "tar. thus tat appears", "thus tat appears to", "tat appears to facilitate transcriptional", "appears to facilitate transcriptional elongation", "to facilitate transcriptional elongation of", "facilitate transcriptional elongation of the", "transcriptional elongation of the hiv", "the hiv 1 transcript by", "hiv 1 transcript by hyperphosphorylating", "1 transcript by hyperphosphorylating the", "transcript by hyperphosphorylating the rna", "by hyperphosphorylating the rna poll", "hyperphosphorylating the rna poll ii", "the rna poll ii ctd", "rna poll ii ctd and", "poll ii ctd and by", "ii ctd and by 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under", "cytosol.

under normal", "normal conditions", "self nucleic", "acids are", "are not", "not recognized", "recognized by", "by tlrs", "tlrs due", "due to", "to multiple", "multiple levels", "levels of", "of regulation", "regulation including", "including receptor", "receptor compartmentalization", "and proteolytic", "proteolytic processing", "barton gm", "gm et", "et al", "al 2006", "ewald se", "se et", "al 2008", "2008 .", ". at", "at steady", "steady state", "state tlr3", "tlr9 reside", "reside primarily", "primarily in", "in the", "the endoplasmic", "endoplasmic reticulum", "their activation", "activation by", "by specific", "specific ligands", "ligands only", "only occurs", "occurs within", "within acidified", "acidified endolysosomal", "endolysosomal compartments", "hacker h", "h et", "al 1998", "funami k", "k et", "al 2004", "gibbard rj", "rj et", "2006 .", ". several", "several chaperon", "chaperon proteins", "proteins associate", "associate with", "with tlrs", "tlrs in", "the er", "er to", "to provide", "provide efficient", "efficient translocation", "translocation to", "to endolysosome.", "endolysosome. upon", "upon reaching", "reaching endolysosomal", "compartments the", "the ectodomains", "ectodomains of", "of tlr7", "tlr7 and", "and tlr9", "are proteolytically", "proteolytically cleaved", "cleaved by", "by cysteine", "cysteine endoproteases.", "endoproteases. both", "both full", "full length", "length and", "and cleaved", "cleaved c", "c terminus", "terminus of", "of tlr9", "tlr9 bind", "bind cpg", "cpg oligodeoxynucleotides", "however it", "it has", "has been", "been proposed", "proposed that", "that only", "only the", "the processed", "processed receptor", "receptor is", "is functional.

", "functional.

although", "although similar", "similar cleavage", "cleavage of", "of tlr3", "tlr3 has", "been reported", "reported by", "by ewald", "ewald et", "al 2011", "other studies", "studies demonstrated", "demonstrated that", "that the", "the n", "n terminal", "terminal region", "region of", "tlr3 ectodomain", "ectodomain was", "was implicated", "implicated in", "in ligand", "ligand binding", "thus tlr3", "tlr3 may", "may function", "function as", "as a", "a full", "length receptor", "liu l", "l et", "tokisue t", "t et", "2008 .

", ".

there", "there are", "are no", "no data", "data on", "on tlr8", "tlr8 processing", "although the", "cell biology", "biology of", "of tlr8", "tlr8 is", "is probably", "probably similar", "similar to", "to tlr9", "tlr9 and", "and tlr7", "wei t", "al 2009", "2009 .", "tlr3 tlr7", "tlr7 tlr8", "tlr8 tlr9", "tlr9 are endosomal", "are endosomal receptors", "endosomal receptors that", "receptors that sense", "that sense nucleic", "sense nucleic acids", "nucleic acids that", "acids that have", "that have been", "have been released", "been released from", "released from endocytosed/phagocytosed", "from endocytosed/phagocytosed bacteria", "bacteria viruses", "viruses or parasites.", "or parasites. these", "parasites. these tlrs", "these tlrs have", "tlrs have a", "have a ligand", "a ligand recognition", "ligand recognition domain", "recognition domain that", "domain that faces", "that faces the", "faces the lumen", "the lumen of", "lumen of the", "of the endosome", "endosome which", "which is topologically", "is topologically equivalent", "topologically equivalent to", "equivalent to the", "to the outside", "the outside of", "outside of the", "of the cell", "a transmembrane domain", "domain and", "and a signaling", "a signaling domain", "signaling domain that", "faces the cytosol.

under", "the cytosol.

under normal", "cytosol.

under normal conditions", "conditions self", "self nucleic acids", "nucleic acids are", "acids are not", "are not recognized", "not recognized by", "recognized by tlrs", "by tlrs due", "tlrs due to", "due to multiple", "to multiple levels", "multiple levels of", "levels of regulation", "of regulation including", "regulation including receptor", "including receptor compartmentalization", "compartmentalization trafficking", "trafficking and proteolytic", "and proteolytic processing", "processing barton", "barton gm et", "gm et al", "et al 2006", "2006 ewald", "ewald se et", "se et al", "et al 2008", "al 2008 .", "2008 . at", ". at steady", "at steady state", "steady state tlr3", "tlr9 reside primarily", "reside primarily in", "primarily in the", "in the endoplasmic", "the endoplasmic reticulum", "reticulum er", "however their", "their activation by", "activation by specific", "by specific ligands", "specific ligands only", "ligands only occurs", "only occurs within", "occurs within acidified", "within acidified endolysosomal", "acidified endolysosomal compartments", "compartments hacker", "hacker h et", "h et al", "et al 1998", "1998 funami", "funami k et", "k et al", "et al 2004", "2004 gibbard", "gibbard rj et", "rj et al", "al 2006 .", "2006 . several", ". several chaperon", "several chaperon proteins", "chaperon proteins associate", "proteins associate with", "associate with tlrs", "with tlrs in", "tlrs in the", "in the er", "the er to", "er to provide", "to provide efficient", "provide efficient translocation", "efficient translocation to", "translocation to endolysosome.", "to endolysosome. upon", "endolysosome. upon reaching", "upon reaching endolysosomal", "reaching endolysosomal compartments", "endolysosomal compartments the", "compartments the ectodomains", "the ectodomains of", "ectodomains of tlr7", "of tlr7 and", "tlr7 and tlr9", "and tlr9 are", "tlr9 are proteolytically", "are proteolytically cleaved", "proteolytically cleaved by", "cleaved by cysteine", "by cysteine endoproteases.", "cysteine endoproteases. both", "endoproteases. both full", "both full length", "full length and", "length and cleaved", "and cleaved c", "cleaved c terminus", "c terminus of", "terminus of tlr9", "of tlr9 bind", "tlr9 bind cpg", "bind cpg oligodeoxynucleotides", "oligodeoxynucleotides however", "however it has", "it has been", "has been proposed", "been proposed that", "proposed that only", "that only the", "only the processed", "the processed receptor", "processed receptor is", "receptor is functional.

", "is functional.

although", "functional.

although similar", "although similar cleavage", "similar cleavage of", "cleavage of tlr3", "of tlr3 has", "tlr3 has been", "has been reported", "been reported by", "reported by ewald", "by ewald et", "ewald et al", "et al 2011", "2011 other", "other studies demonstrated", "studies demonstrated that", "demonstrated that the", "that the n", "the n terminal", "n terminal region", "terminal region of", "region of tlr3", "of tlr3 ectodomain", "tlr3 ectodomain was", "ectodomain was implicated", "was implicated in", "implicated in ligand", "in ligand binding", "binding thus", "thus tlr3 may", "tlr3 may function", "may function as", "function as a", "as a full", "a full length", "full length receptor", "receptor liu", "liu l et", "l et al", "2008 tokisue", "tokisue t et", "t et al", "al 2008 .

", "2008 .

there", ".

there are", "there are no", "are no data", "no data on", "data on tlr8", "on tlr8 processing", "processing although", "although the cell", "the cell biology", "cell biology of", "biology of tlr8", "of tlr8 is", "tlr8 is probably", "is probably similar", "probably similar to", "similar to tlr9", "to tlr9 and", "tlr9 and tlr7", "tlr7 gibbard", "2006 wei", "wei t et", "et al 2009", "al 2009 .", "mammalian tlr3 tlr7", "tlr8 tlr9 are", "tlr9 are endosomal receptors", "are endosomal receptors that", "endosomal receptors that sense", "receptors that sense nucleic", "that sense nucleic acids", "sense nucleic acids that", "nucleic acids that have", "acids that have been", "that have been released", "have been released from", "been released from endocytosed/phagocytosed", "released from endocytosed/phagocytosed bacteria", "endocytosed/phagocytosed bacteria viruses", "bacteria viruses or", "viruses or parasites. these", "or parasites. these tlrs", "parasites. these tlrs have", "these tlrs have a", "tlrs have a ligand", "have a ligand recognition", "a ligand recognition domain", "ligand recognition domain that", "recognition domain that faces", "domain that faces the", "that faces the lumen", "faces the lumen of", "the lumen of the", "lumen of the endosome", "the endosome which", "endosome which is", "which is topologically equivalent", "is topologically equivalent to", "topologically equivalent to the", "equivalent to the outside", "to the outside of", "the outside of the", "outside of the cell", "cell a", "transmembrane domain and", "domain and a", "and a signaling domain", "a signaling domain that", "signaling domain that faces", "that faces the cytosol.

under", "faces the cytosol.

under normal", "the cytosol.

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", "receptor is functional.

although", "is functional.

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although similar cleavage", "although similar cleavage of", "similar cleavage of tlr3", "cleavage of tlr3 has", "of tlr3 has been", "tlr3 has been reported", "has been reported by", "been reported by ewald", "reported by ewald et", "by ewald et al", "ewald et al 2011", "al 2011 other", "2011 other studies", "other studies demonstrated that", "studies demonstrated that the", "demonstrated that the n", "that the n terminal", "the n terminal region", "n terminal region of", "terminal region of tlr3", "region of tlr3 ectodomain", "of tlr3 ectodomain was", "tlr3 ectodomain was implicated", "ectodomain was implicated in", "was implicated in ligand", "implicated in ligand binding", "ligand binding thus", "binding thus tlr3", "thus tlr3 may function", "tlr3 may function as", "may function as a", "function as a full", "as a full length", "a full length receptor", "length receptor liu", "receptor liu l", "liu l et al", "l et al 2008", "al 2008 tokisue", "2008 tokisue t", "tokisue t et al", "t et al 2008", "et al 2008 .

", "al 2008 .

there", "2008 .

there are", ".

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under", "that faces the cytosol.

under normal", "faces the cytosol.

under normal conditions", "cytosol.

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", "processed receptor is functional.

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", "et al 2008 .

there", "al 2008 .

there are", "2008 .

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"2006 . however the", ". however the signals", "however the signals on", "the signals on np", "signals on np have", "on np have been", "np have been shown", "have been shown to", "been shown to be", "shown to be both", "to be both sufficient", "be both sufficient and", "both sufficient and necessary", "sufficient and necessary for", "and necessary for the", "necessary for the import", "for the import of", "the import of viral", "import of viral rna.", "an unusual characteristic of the", "unusual characteristic of the influenza", "characteristic of the influenza virus", "of the influenza virus life", "the influenza virus life cycle", "influenza virus life cycle is", "virus life cycle is its", "life cycle is its dependence", "cycle is its dependence on", "is its dependence on the", "its dependence on the nucleus.", "dependence on the nucleus. trafficking", "on the nucleus. trafficking of", "the nucleus. trafficking of the", "nucleus. trafficking of the viral", "trafficking of the viral 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exist as naked rna", "exist as naked rna but", "as naked rna but are", "naked rna but are associated", "rna but are associated with", "but are associated with four", "are associated with four viral", "associated with four viral proteins", "with four viral proteins to", "four viral proteins to form", "viral proteins to form viral", "proteins to form viral ribonucleoprotein", "to form viral ribonucleoprotein complexes", "viral ribonucleoprotein complexes vrnps", "ribonucleoprotein complexes vrnps .", "complexes vrnps . the", "vrnps . the major viral", ". the major viral protein", "the major viral protein in", "major viral protein in the", "viral protein in the rnp", "protein in the rnp complex", "in the rnp complex is", "the rnp complex is the", "rnp complex is the nucleocapsid", "complex is the nucleocapsid protein", "the nucleocapsid protein np", "np which coats", "which coats the rna. the", "coats the rna. the remaining", "the rna. the remaining proteins", "rna. the remaining proteins pb1", "remaining proteins pb1 pb2", "proteins pb1 pb2 and", "pb1 pb2 and pa", "pb2 and pa bind to", "and pa bind to the", "pa bind to the partially", "bind to the partially complementary", "to the partially complementary ends", "the partially complementary ends of", "partially complementary ends of the", "complementary ends of the viral", "ends of the viral rna", "the viral rna creating", "viral rna creating the", "rna creating the distinctive", "creating the distinctive panhandle structure.", "the distinctive panhandle structure. these", "distinctive panhandle structure. these rnps", "structure. these rnps 10", "these rnps 10 20nm", "rnps 10 20nm wide", "10 20nm wide are", "20nm wide are too", "wide are too large", "are too large to passively", "too large to passively diffuse", "large to passively diffuse into", "to passively diffuse into the", "passively diffuse into the nucleus", "diffuse into the nucleus and", "into the nucleus and therefore", "nucleus and therefore once", "and therefore once released", "therefore once released from", "once released from an incoming", "released from an incoming particle", "from an incoming particle must", "an incoming particle must rely", "incoming particle must rely on", "particle must rely on the", "must rely on the active", "rely on the active import", "on the active import mechanism", "the active import mechanism of", "active import mechanism of the", "import mechanism of the host", "mechanism of the host cell", "of the host cell nuclear", "the host cell nuclear pore", "host cell nuclear pore complex.", "cell nuclear pore complex. all", "nuclear pore complex. all proteins", "pore complex. all proteins in", "complex. all proteins in the", "all proteins in the rnp", "proteins in the rnp complex", "in the rnp complex can", "the rnp complex can independently", "rnp complex can independently localize", "complex can independently localize to", "can independently localize to the", "independently localize to the nucleus", 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leading", "proximity leading to", "leading to nf kappab", "to nf kappab activation", "nf kappab activation and", "kappab activation and activation", "activation and activation of", "and activation of mapk", "activation of mapk signaling.", "of mapk signaling. recent", "mapk signaling. recent studies", "signaling. recent studies have", "recent studies have demonstrated", "studies have demonstrated that", "have demonstrated that k63", "demonstrated that k63 linked", "that k63 linked regulatory", "k63 linked regulatory ubiquitination", "linked regulatory ubiquitination of", "regulatory ubiquitination of rip2", "ubiquitination of rip2 is", "of rip2 is essential", "rip2 is essential for", "is essential for the", "essential for the recruitment", "for the recruitment of", "the recruitment of tak1", "of tak1 hasegawa", "tak1 hasegawa et", "hasegawa et al. 2008", "al. 2008 hitosumatsu", "2008 hitosumatsu et", "hitosumatsu et al. 2008", "et al. 2008 .", "al. 2008 . as", "2008 . as observed", ". as observed for", "as observed for toll", "observed for toll like", "for toll like receptor", "like receptor tlr", "signaling ubiquitination can", "ubiquitination can be removed", "can be removed by", "be removed by the", "removed by the deubiquitinating", "by the deubiquitinating enzyme", "the deubiquitinating enzyme a20", "enzyme a20 thereby", "a20 thereby dampening", "thereby dampening nod1/nod2 induced", "dampening nod1/nod2 induced nf", "nod1/nod2 induced nf kappab", "induced nf kappab activation.", "nf kappab activation. nod1", "kappab activation. nod1 and", "activation. nod1 and nod2", "nod1 and nod2 both", "and nod2 both induce", "nod2 both induce k63", "both induce k63 linked", "induce k63 linked ubiquitination", "k63 linked ubiquitination of", "linked ubiquitination of rip2", "of rip2 but", "rip2 but nod2", "but nod2 signaling appears", "nod2 signaling appears to", "signaling appears to preferentially", "appears to preferentially utilize", "to preferentially utilize the", "preferentially utilize the e3", "utilize the e3 ligase", "the e3 ligase traf6", "ligase traf6 while", "traf6 while traf2", "while traf2 and traf5", "traf2 and traf5 were", "and traf5 were shown", "traf5 were shown to", "were shown to be", "shown to be important", "to be important for", "be important for nod1", "important for nod1 mediated", "for nod1 mediated signaling.", "nod1 mediated signaling. in", "mediated signaling. in both", "signaling. in both cases", "both cases activation", "cases activation of", "activation of nf kappab", "of nf kappab results", "nf kappab results in", "kappab results in the", "results in the upregulated", "in the upregulated transcription", "the upregulated transcription and", "upregulated transcription and production", "transcription and production of", "and production of inflammatory", "production of inflammatory mediators.", "is ubiquitously expressed while", "ubiquitously expressed while nod2", "expressed while nod2 expression", "while nod2 expression is restricted", "nod2 expression is restricted to", "expression is restricted to monocytes", "restricted to monocytes macrophages", "monocytes macrophages dendritic", "dendritic cells and intestinal", "cells and intestinal paneth", "intestinal paneth cells inohara", "paneth cells inohara et", "cells inohara et al.", "inohara et al. 2005 .", "et al. 2005 . nod1", "al. 2005 . nod1 and", "2005 . nod1 and nod2", ". nod1 and nod2 activation", "nod1 and nod2 activation induces", "and nod2 activation induces transcription", "nod2 activation induces transcription of", "activation induces transcription of immune", "induces transcription of immune response", "transcription of immune response genes", "immune response genes predominantly", "response genes predominantly mediated", "genes predominantly mediated by", "predominantly mediated by the proinflammatory", "mediated by the proinflammatory transcriptional", "by the proinflammatory transcriptional factor", "the proinflammatory transcriptional factor nfkappab", "proinflammatory transcriptional factor nfkappab but", "transcriptional factor nfkappab but also", "factor nfkappab but also by", "nfkappab but also by ap", "but also by ap 1", "also by ap 1 and", "by ap 1 and elk", "ap 1 and elk 1", "and elk 1 inohara", "elk 1 inohara et", "1 inohara et al.", "et al. 2005 . nfkappab", "al. 2005 . nfkappab translocates", "2005 . nfkappab translocates to", ". nfkappab translocates to the", "nfkappab translocates to the nucleus", "translocates to the nucleus following", "to the nucleus following release", "the nucleus following release from", "nucleus following release from ikappab", "following release from ikappab proteins.", "release from ikappab proteins. nod1", "from ikappab proteins. nod1 and", "ikappab proteins. nod1 and nod2", "proteins. nod1 and nod2 signaling", "nod1 and nod2 signaling involves", "and nod2 signaling involves an", "nod2 signaling involves an interaction", "signaling involves an interaction between", "involves an interaction between their", "an interaction between their caspase", "interaction between their caspase recruitment", "between their caspase recruitment domain", "caspase recruitment domain card", "domain card and", "card and the card", "and the card of the", "the card of the kinase", "card of the kinase ripk2", "the kinase ripk2 rip2/rick", "kinase ripk2 rip2/rick .", "ripk2 rip2/rick . this", "rip2/rick . this leads to", ". this leads to the", "this leads to the activation", "leads to the activation of", "to the activation of the", "the activation of the nfkappab", "activation of the nfkappab pathway", "of the nfkappab pathway and", "the nfkappab pathway and mapk", "nfkappab pathway and mapk pathways", "and mapk pathways windheim", "mapk pathways windheim et", "pathways windheim et al.", "windheim et al. 2007 .
activated", "et al. 2007 .
activated nods", "al. 2007 .
activated nods oligomerize", "2007 .
activated nods oligomerize via", ".
activated nods oligomerize via their", "nods oligomerize via their nacht", "oligomerize via their nacht domains", "their nacht domains inducing", "nacht domains inducing physical", "domains inducing physical proximity", "inducing physical proximity of rip2", "physical proximity of rip2 proteins", "proximity of rip2 proteins that", "of rip2 proteins that is", "rip2 proteins that is believed", "proteins that is believed to", "that is believed to trigger", "is believed to trigger their", "believed to trigger their k63", "to trigger their k63 linked", "trigger their k63 linked polyubiquitination", "k63 linked polyubiquitination facilitating", "linked polyubiquitination facilitating recruitment", "polyubiquitination facilitating recruitment of", "facilitating recruitment of the tak1", "recruitment of the tak1 complex.", "of the tak1 complex. rip2", "the tak1 complex. rip2 also", "tak1 complex. rip2 also recruits", "complex. rip2 also recruits nemo", "also recruits nemo bringing", "recruits nemo bringing the", "nemo bringing the tak1", "bringing the tak1 and ikk", "the tak1 and ikk complexes", "tak1 and ikk complexes into", "and ikk complexes into proximity", "complexes into proximity leading", "into proximity leading to", "proximity leading to nf", "leading to nf kappab activation", "to nf kappab activation and", "nf kappab activation and activation", "kappab activation and activation of", "activation and activation of mapk", "and activation of mapk signaling.", "activation of mapk signaling. recent", "of mapk signaling. recent studies", "mapk signaling. recent studies have", "signaling. recent studies have demonstrated", "recent studies have demonstrated that", "studies have demonstrated that k63", "have demonstrated that k63 linked", "demonstrated that k63 linked regulatory", "that k63 linked regulatory ubiquitination", "k63 linked regulatory ubiquitination of", "linked regulatory ubiquitination of rip2", "regulatory ubiquitination of rip2 is", "ubiquitination of rip2 is essential", "of rip2 is essential for", "rip2 is essential for the", "is essential for the recruitment", "essential for the recruitment of", "for the recruitment of tak1", "recruitment of tak1 hasegawa", "of tak1 hasegawa et", "tak1 hasegawa et al.", "et al. 2008 hitosumatsu", "al. 2008 hitosumatsu et", "2008 hitosumatsu et al.", "hitosumatsu et al. 2008 .", "et al. 2008 . as", "al. 2008 . as observed", "2008 . as observed for", ". as observed for toll", "as observed for toll like", "observed for toll like receptor", "toll like receptor tlr", "receptor tlr signaling", "tlr signaling ubiquitination", "signaling ubiquitination can be", "ubiquitination can be removed by", "can be removed by the", "be removed by the deubiquitinating", "removed by the deubiquitinating enzyme", "by the deubiquitinating enzyme a20", "deubiquitinating enzyme a20 thereby", "enzyme a20 thereby dampening", "a20 thereby dampening nod1/nod2", "thereby dampening nod1/nod2 induced nf", "dampening nod1/nod2 induced nf kappab", "nod1/nod2 induced nf kappab activation.", "induced nf kappab activation. nod1", "nf kappab activation. nod1 and", "kappab activation. nod1 and nod2", "activation. nod1 and nod2 both", "nod1 and nod2 both induce", "and nod2 both induce k63", "nod2 both induce k63 linked", "both induce k63 linked ubiquitination", "induce k63 linked ubiquitination of", "k63 linked ubiquitination of rip2", "ubiquitination of rip2 but", "of rip2 but nod2", "rip2 but nod2 signaling", "but nod2 signaling appears to", "nod2 signaling appears to preferentially", "signaling appears to preferentially utilize", "appears to preferentially utilize the", "to preferentially utilize the e3", "preferentially utilize the e3 ligase", "utilize the e3 ligase traf6", "e3 ligase traf6 while", "ligase traf6 while traf2", "traf6 while traf2 and", "while traf2 and traf5 were", "traf2 and traf5 were shown", "and traf5 were shown to", "traf5 were shown to be", "were shown to be important", "shown to be important for", "to be important for nod1", "be important for nod1 mediated", "important for nod1 mediated signaling.", "for nod1 mediated signaling. in", "nod1 mediated signaling. in both", "mediated signaling. in both cases", "in both cases activation", "both cases activation of", "cases activation of nf", "activation of nf kappab results", "of nf kappab results in", "nf kappab results in the", "kappab results in the upregulated", "results in the upregulated transcription", "in the upregulated transcription and", "the upregulated transcription and production", "upregulated transcription and production of", "transcription and production of inflammatory", "and production of inflammatory mediators." ] }, { "record_id": "GLY_000594_1_110", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "168927", "r hsa", "hsa 168927", "r hsa 168927" ] }, { "record_id": "GLY_000594_1_110", "filename": "human_protein_pathways_reactome", "fieldtype": "text", 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"rna helicases that recognize viral", "helicases that recognize viral double", "that recognize viral double stranded", "recognize viral double stranded rna", "double stranded rna dsrna", "rna dsrna present", "dsrna present within the", "within the cytoplasm yoneyama", "the cytoplasm yoneyama m", "cytoplasm yoneyama m &", "yoneyama m & fujita t", "m & fujita t 2007", "fujita t 2007 2008", "t 2007 2008 .", "2007 2008 . upon", "2008 . upon viral infection", ". upon viral infection dsrna", "upon viral infection dsrna is", "viral infection dsrna is generated", "infection dsrna is generated by", "dsrna is generated by positive", "is generated by positive strand", "generated by positive strand rna", "by positive strand rna virus", "positive strand rna virus families", "strand rna virus families such", "rna virus families such as", "virus families such as flaviviridae", "families such as flaviviridae and", "such as flaviviridae and coronaviridae", "flaviviridae and coronaviridae negative", "and coronaviridae negative strand", "coronaviridae negative strand rna", "negative strand rna virus families", "strand rna virus families including", "rna virus families including orthomyxoviridae", "virus families including orthomyxoviridae and", "families including orthomyxoviridae and paramyxoviridae", "orthomyxoviridae and paramyxoviridae and", "and paramyxoviridae and dna", "paramyxoviridae and dna virus", "and dna virus families such", "dna virus families such as", "virus families such as herpesviridae", "families such as herpesviridae and", "such as herpesviridae and adenoviridae", "herpesviridae and adenoviridae weber", "and adenoviridae weber f", "adenoviridae weber f et", "weber f et al. 2006", "et al. 2006 son", "al. 2006 son kn", "2006 son kn et", "son kn et al. 2015", "kn et al. 2015 .", "et al. 2015 . functionally", "al. 2015 . functionally rig", "2015 . functionally rig i", "functionally rig i ddx58", "mda5 ifih1 positively", "ifih1 positively regulate the", "positively regulate the ifn genes", "regulate the ifn genes in", "the ifn genes in a", "ifn genes in a similar", "genes in a similar fashion", "a similar fashion however", "similar fashion however they", "fashion however they differ", "however they differ in their", "they differ in their response", "differ in their response to", "in their response to different", "their response to different viral", "response to different viral species.", "to different viral species. ddx58", "viral species. ddx58 rig", "species. ddx58 rig i", "rig i is essential", "i is essential for", "is essential for detecting influenza", "essential for detecting influenza virus", "detecting influenza virus sendai", "influenza virus sendai virus", "sendai virus vsv and", "virus vsv and japanese", "vsv and japanese encephalitis virus", "japanese encephalitis virus jev", "jev whereas ifih1", "ifih1 mda5 is", "mda5 is essential in", "is essential in sensing encephalomyocarditis", "essential in sensing encephalomyocarditis virus", "sensing encephalomyocarditis virus emcv", "emcv mengo virus", "mengo virus and theiler's virus", "and theiler's virus all", "theiler's virus all of", "virus all of which", "all of which belong to", "of which belong to the", "which belong to the picornavirus", "belong to the picornavirus family.", "to the picornavirus family. rig", "the picornavirus family. rig i", "picornavirus family. rig i and", "family. rig i and mda5", "rig i and mda5 signalling", "i and mda5 signalling results", "and mda5 signalling results in", "mda5 signalling results in the", "signalling results in the activation", "results in the activation of", "in the activation of ikk", "the activation of ikk epsilon", "activation of ikk epsilon and", "ikk epsilon and tkk", "epsilon and tkk binding", "and tkk binding kinase", "binding kinase 1 tbk1", "1 tbk1 two", "tbk1 two serine/threonine kinases", "two serine/threonine kinases that phosphorylate", "serine/threonine kinases that phosphorylate interferon", "kinases that phosphorylate interferon regulatory", "that phosphorylate interferon regulatory factor", "phosphorylate interferon regulatory factor 3", "interferon regulatory factor 3 and", "regulatory factor 3 and 7", "3 and 7 irf3", "and 7 irf3 and", "7 irf3 and irf7", "irf3 and irf7 . upon", "and irf7 . upon phosphorylation", ". upon phosphorylation irf3", "upon phosphorylation irf3 and", "phosphorylation irf3 and irf7", "irf3 and irf7 translocate to", "and irf7 translocate to the", "irf7 translocate to the nucleus", "translocate to the nucleus and", "to the nucleus and subsequently", "the nucleus and subsequently induce", "nucleus and subsequently induce interferon", "and subsequently induce interferon alpha", "induce interferon alpha ifna", "alpha ifna and", "ifna and interferon beta", "and interferon beta ifnb", "beta ifnb gene", "gene transcription yoneyama m", "transcription yoneyama m et", "yoneyama m et al. 2004", "et al. 2004 yoneyama", "al. 2004 yoneyama m", "2004 yoneyama m &" ] }, { 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"r hsa", "hsa 170822", "r hsa 170822" ] }, { "record_id": "GLY_000594_1_113", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of glucokinase", "glucokinase by", "by glucokinase", "glucokinase regulatory", "regulatory protein", "regulation of glucokinase", "of glucokinase by", "glucokinase by glucokinase", "by glucokinase regulatory", "glucokinase regulatory protein", "regulation of glucokinase by", "of glucokinase by glucokinase", "glucokinase by glucokinase regulatory", "by glucokinase regulatory protein", "regulation of glucokinase by glucokinase", "of glucokinase by glucokinase regulatory", "glucokinase by glucokinase regulatory protein", "is negatively", "negatively regulated", "regulated by", "which reversibly", "reversibly binds", "binds the", "the enzyme", "enzyme to", "to form", "form an", "an inactive", "inactive complex.", "complex. binding", "binding is", "is stimulated", "stimulated by", "by fructose", "fructose 6", "6 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transcription factor creb and", "transcription factor creb and the", "factor creb and the activation", "creb and the activation of", "and the activation of immediate", "the activation of immediate early", "activation of immediate early genes", "immediate early genes xing", "early genes xing j", "xing j 1998 .", "j 1998 . p38", "1998 . p38 activation by", ". p38 activation by ngf", "p38 activation by ngf may", "activation by ngf may occur", "by ngf may occur by", "ngf may occur by at", "may occur by at least", "occur by at least two", "by at least two mechanisms", "least two mechanisms involving", "two mechanisms involving src", "mechanisms involving src or", "involving src or mek kinases." ] }, { "record_id": "GLY_000594_1_115", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "171319", "r hsa", "hsa 171319", "r hsa 171319" ] }, { "record_id": "GLY_000594_1_115", "filename": "human_protein_pathways_reactome", "fieldtype": "text", 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telomerase", "chromosome end.

telomerase can", "end.

telomerase can perform", "

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telomerase", "the chromosome end.

telomerase can", "chromosome end.

telomerase can perform", "end.

telomerase can perform multiple", "

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six subunits are", "the six subunits are held", "six subunits are held together", "subunits are held together by", "are held together by the", "held together by the collagenous", "together by the collagenous stalk", "by the collagenous stalk parts", "collagenous stalk parts giving", "stalk parts giving rise", "parts giving rise to", "giving rise to the comparison", "rise to the comparison of", "to the comparison of c1q", "the comparison of c1q with", "comparison of c1q with a", "of c1q with a \\bunch", "c1q with a \\bunch of", "with a \\bunch of six", "a \\bunch of six tulips\\", "\\bunch of six tulips\\ .", "of six tulips\\ . the", "six tulips\\ . the stalks", "tulips\\ . the stalks also", ". the stalks also interact", "the stalks also interact with", "stalks also interact with the", "interact with the c1s:c1r:c1r:c1s", "the c1s:c1r:c1r:c1s tetramer", "c1s:c1r:c1r:c1s tetramer assembled in", "tetramer assembled in a linear", "assembled in a linear chain.", "in a linear chain. binding", "a linear chain. binding of", "linear chain. binding of an", "chain. binding of an antigen", "binding of an antigen to", "of an antigen to an", "an antigen to an antibody", "antigen to an antibody of", "to an antibody of the", "an antibody of the igm", "antibody of the igm or", "of the igm or igg", "the igm or igg class", "igm or igg class induces", "or igg class induces a", "igg class induces a conformational", "class induces a conformational change", "induces a conformational change in", "a conformational change in the", "conformational change in the fc", "change in the fc domain", "in the fc domain of", "the fc domain of the", "fc domain of the antibody", "domain of the antibody that", "of the antibody that allows", "the antibody that allows it", "antibody that allows it to", "that allows it to bind", "allows it to bind to", "it to bind to the", "to bind to the c1q", "bind to the c1q component", "to the c1q component of", "the c1q component of c1.", "c1q component of c1. c1", "component of c1. c1 activation", "of c1. c1 activation requires", "c1. c1 activation requires interaction", "c1 activation requires interaction with", "activation requires interaction with two", "requires interaction with two separate", "interaction with two separate fc", "with two separate fc domains", "separate fc domains so", "fc domains so pentavalent", "domains so pentavalent igm", "so pentavalent igm antibody is", "pentavalent igm antibody is far", "igm antibody is far more", "antibody is far more efficient", "is far more efficient at", "far more efficient at complement", "more efficient at complement activation", "efficient at complement activation than", "at complement activation than igg", "complement activation than igg antibody.", "activation than igg antibody. antibody", "than igg antibody. antibody binding", "igg antibody. antibody binding results", "antibody. antibody binding results in", "antibody binding results in a", "binding results in a conformational", "results in a conformational change", "in a conformational change in", "conformational change in the c1r", "change in the c1r component", "in the c1r component of", "the c1r component of the", "c1r component of the c1", "component of the c1 complex", "of the c1 complex and", "the c1 complex and a", "c1 complex and a proteolytic", "complex and a proteolytic cleavage", "and a proteolytic cleavage of", "a proteolytic cleavage of c1r", "cleavage of c1r activating", "of c1r activating it.", "c1r activating it. active", "activating it. active c1r then", "it. active c1r then cleaves", "active c1r then cleaves and", "c1r then cleaves and activates", "then cleaves and activates the", "cleaves and activates the c1s", "and activates the c1s component", "activates the c1s component of", "the c1s component of the", "c1s component of the c1", "the c1 complex muller", "c1 complex muller eberhard", "complex muller eberhard 1988" ] }, { "record_id": "GLY_000594_1_117", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "174048", "r hsa", "hsa 174048", "r hsa 174048" ] }, { "record_id": "GLY_000594_1_117", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "apc/c:cdc20 mediated", "mediated degradation", "degradation of", "of cyclin", "cyclin b", "apc/c:cdc20 mediated degradation", "mediated degradation of", "degradation of cyclin", "of cyclin b", "apc/c:cdc20 mediated degradation of", "mediated degradation of cyclin", "degradation of cyclin b", "apc/c:cdc20 mediated degradation of cyclin", "mediated degradation of cyclin b", "the degradation", "cyclin b1", "which appears", "appears to", "to occur", "occur at", "at the", "the mitotic", "mitotic spindle", "is delayed", "delayed until", "until the", "the metaphase", "metaphase /anaphase", "/anaphase transition", "transition by", "by the", "the spindle", "spindle assembly", "assembly checkpoint", "checkpoint and", "and is", "is required", "required in", "in order", "order for", "for sister", "sister chromatids", "chromatids to", "to separate", "geley et", "et al.", "al. 2001", "2001 hagting", "hagting et", "et al", "2002 .", "the degradation of", "of cyclin b1", "b1 which", "which appears to", "appears to occur", "to occur at", "occur at the", "at the mitotic", "the mitotic spindle", "spindle is", "is delayed until", "delayed until the", "until the metaphase", "the metaphase /anaphase", "metaphase /anaphase transition", "/anaphase transition by", "transition by the", "by the spindle", "the spindle assembly", "spindle assembly checkpoint", "assembly checkpoint and", "checkpoint and is", "and is required", "is required in", "required in order", "in order for", "order for sister", "for sister chromatids", "sister chromatids to", "chromatids to separate", "separate geley", "geley et al.", "et al. 2001", "al. 2001 hagting", "2001 hagting et", "hagting et al", "al 2002", "the degradation of cyclin", "degradation of 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hagting", "et al. 2001 hagting et", "al. 2001 hagting et al", "hagting et al 2002", "et al 2002 ." ] }, { "record_id": "GLY_000594_1_118", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "174084", "r hsa", "hsa 174084", "r hsa 174084" ] }, { "record_id": "GLY_000594_1_118", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "autodegradation of", "of cdh1", "cdh1 by", "by cdh1:apc/c", "autodegradation of cdh1", "of cdh1 by", "cdh1 by cdh1:apc/c", "autodegradation of cdh1 by", "of cdh1 by cdh1:apc/c", "autodegradation of cdh1 by cdh1:apc/c", "cdh1 is", "is degraded", "degraded by", "by the", "the apc/c", "apc/c during", "during in", "in g1", "g1 and", "and g0.", "g0. this", "this auto", "auto regulation", "regulation may", "may contribute", "contribute to", "to reducing", "reducing the", "the levels", "levels of", "cdh1 levels", "levels during", "during g1", "and g0", "listovsky et", "et al.", "2004 .", "cdh1 is degraded", "is degraded by", "degraded by the", "by the apc/c", "the apc/c during", "apc/c during in", "during in g1", "in g1 and", "g1 and g0.", "and g0. this", "g0. this auto", "this auto regulation", "auto regulation may", "regulation may contribute", "may contribute to", "contribute to reducing", "to reducing the", "reducing the levels", "the levels of", "levels of cdh1", "of cdh1 levels", "cdh1 levels during", "levels during g1", "during g1 and", "g1 and g0", "g0 listovsky", "listovsky et al.", "al. 2004", "cdh1 is degraded by", "is degraded by the", "degraded by the apc/c", "by the apc/c during", "the apc/c during in", "apc/c during in g1", "during in g1 and", "in g1 and g0.", "g1 and g0. this", "and g0. this auto", "g0. this auto regulation", "this auto regulation may", "auto regulation may contribute", "regulation may contribute to", "may contribute to reducing", "contribute to reducing the", "to reducing the levels", "reducing the levels of", "the levels of cdh1", "levels of cdh1 levels", "of cdh1 levels during", "cdh1 levels during g1", "levels during g1 and", "during g1 and g0", "and g0 listovsky", "g0 listovsky et", "et al. 2004", "al. 2004 .", "cdh1 is degraded by the", "is degraded by the apc/c", "degraded by the apc/c during", "by the apc/c during in", "the apc/c during in g1", "apc/c during in g1 and", "during in g1 and g0.", "in g1 and g0. this", "g1 and g0. this auto", "and g0. this auto regulation", "g0. this auto regulation may", "this auto regulation may contribute", "auto regulation may contribute to", "regulation may contribute to reducing", "may contribute to reducing the", "contribute to reducing the levels", "to reducing the levels of", "reducing the levels of cdh1", "the levels of cdh1 levels", "levels of cdh1 levels during", "of cdh1 levels during g1", "cdh1 levels during g1 and", "levels during g1 and g0", "g1 and g0 listovsky", "and g0 listovsky et", "g0 listovsky et al.", "listovsky et al. 2004", "et al. 2004 ." ] }, { "record_id": "GLY_000594_1_119", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "174113", "r hsa", "hsa 174113", "r hsa 174113" ] }, { "record_id": "GLY_000594_1_119", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "scf beta", "beta trcp", "trcp mediated", "mediated degradation", "degradation of", "of emi1", "scf beta trcp", "beta trcp mediated", "trcp mediated degradation", "mediated degradation of", "degradation of emi1", "scf beta trcp mediated", "beta trcp mediated degradation", "trcp mediated degradation of", "mediated degradation of emi1", "scf beta trcp mediated degradation", "beta trcp mediated degradation of", "trcp mediated degradation of emi1", "emi1 destruction", "destruction in", "in early", "early mitosis", "mitosis requires", "requires the", "the scf", "trcp ubiquitin", "ubiquitin ligase", "ligase complex.", "complex. binding", "binding of", "of beta", "trcp to", "to emi1", "emi1 occurs", "occurs in", "in late", "late prophase", "prophase and", "and requires", "requires phosphorylation", "phosphorylation at", "at the", "the dsgxxs", "dsgxxs consensus", "motif as", "as well", "well as", "as cdk", "cdk mediated", "mediated phosphorylation.", "a two", "two step", "step mechanism", "mechanism has", "has been", "been proposed", "proposed in", "in which", "the phosphorylation", "phosphorylation of", "emi1 by", "by cdc2", "cdc2 occurs", "occurs after", "after the", "the g2", "g2 m", "m transition", "transition followed", "followed soon", "soon after", "after by", "by binding", "to the", "dsgxxs phosphorylation", "phosphorylation sites.", "sites. emi1", "emi1 is", "is then", "then poly", "poly ubiquitinated", "ubiquitinated and", "and degraded", "degraded by", "by the", "the 26s", "26s proteasome.", "emi1 destruction in", "destruction in early", "in early mitosis", "early mitosis requires", "mitosis requires the", "requires the scf", "the scf beta", "beta trcp 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the g2 m", "after the g2 m transition", "the g2 m transition followed", "g2 m transition followed soon", "m transition followed soon after", "transition followed soon after by", "followed soon after by binding", "soon after by binding of", "by binding of beta", "beta trcp to the dsgxxs", "trcp to the dsgxxs phosphorylation", "to the dsgxxs phosphorylation sites.", "the dsgxxs phosphorylation sites. emi1", "dsgxxs phosphorylation sites. emi1 is", "phosphorylation sites. emi1 is then", "sites. emi1 is then poly", "emi1 is then poly ubiquitinated", "is then poly ubiquitinated and", "then poly ubiquitinated and degraded", "poly ubiquitinated and degraded by", "ubiquitinated and degraded by the", "and degraded by the 26s", "degraded by the 26s proteasome." ] }, { "record_id": "GLY_000594_1_120", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "174154", "r hsa", "hsa 174154", "r hsa 174154" ] }, { "record_id": "GLY_000594_1_120", 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"are outlined meister", "meister 1988 .", "combination of glutamate cysteine", "of glutamate cysteine and", "glutamate cysteine and atp", "cysteine and atp is required", "and atp is required to", "atp is required to form", "is required to form glutathione.", "required to form glutathione. the", "to form glutathione. the steps", "form glutathione. the steps involved", "glutathione. the steps involved in", "the steps involved in the", "steps involved in the synthesis", "involved in the synthesis and", "in the synthesis and recycling", "the synthesis and recycling of", "synthesis and recycling of glutathione", "and recycling of glutathione are", "recycling of glutathione are outlined", "glutathione are outlined meister", "outlined meister 1988" ] }, { "record_id": "GLY_000594_1_124", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "174430", "r hsa", "hsa 174430", "r hsa 174430" ] }, { "record_id": "GLY_000594_1_124", "filename": 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"gly_000594", "hsa", "176187", "r hsa", "hsa 176187", "r hsa 176187" ] }, { "record_id": "GLY_000594_1_126", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of atr", "atr in", "in response", "response to", "to replication", "replication stress", "activation of atr", "of atr in", "atr in response", "in response to", "response to replication", "to replication stress", "activation of atr in", "of atr in response", "atr in response to", "in response to replication", "response to replication stress", "activation of atr in response", "of atr in response to", "atr in response to replication", "in response to replication stress", "genotoxic stress", "stress caused", "caused by", "by dna", "dna damage", "damage or", "or stalled", "stalled replication", "replication forks", "forks can", "can lead", "lead to", "to genomic", "genomic instability.", "instability. to", "to guard", "guard against", "against such", "such instability", 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these", "entry.

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"to genomic instability.", "genomic instability. to", "instability. to guard", "to guard against", "guard against such", "against such instability", "instability genotoxically", "genotoxically stressed cells", "stressed cells activate", "cells activate checkpoint", "activate checkpoint factors", "checkpoint factors that", "factors that halt", "that halt or", "halt or slow", "or slow cell", "slow cell cycle", "cell cycle progression.", "cycle progression. among", "progression. among the", "among the pathways", "the pathways affected", "pathways affected are", "affected are dna", "are dna replication", "dna replication by", "replication by reduction", "by reduction of", "reduction of replication", "of replication origin", "replication origin firing", "firing and", "and mitosis by", "mitosis by inhibiting", "by inhibiting activation", "inhibiting activation of", "activation of cyclin", "of cyclin dependent", "cyclin dependent kinases", "kinases cdks", "cdks . a", ". a key", "a key factor", "key factor involved", "factor involved in", "involved in the", "in the response", "the response to", "response to stalled", "to stalled replication", "replication forks is", "forks is the", "is the atm", "atm and", "and rad3 related", "related atr", "atr kinase", "kinase a", "a member of", "member of the", "of the phosphoinositide", "the phosphoinositide 3", "phosphoinositide 3 kinase", "3 kinase related", "kinase related kinase", "kinase pikk", "pikk family.", "family. rather than", "rather than responding", "than responding to", "responding to particular", "to particular lesions", "particular lesions in", "lesions in dna", "dna atr", "atr and its", "and its binding", "its binding partner", "binding partner atrip", "atrip atr", "atr interacting protein", "protein sense", "sense replication fork", "replication fork stalling", "fork stalling indirectly", "stalling indirectly by", "indirectly by associating", "by associating with", "associating with persistent", "with 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suppressor", "tumor suppressor p53", "p53 activated", "activated atr modifies", "atr modifies numerous", "modifies numerous factors", "numerous factors that", "factors that regulate", "that regulate cell", "regulate cell cycle", "cell cycle progression", "cycle progression or", "progression or the", "or the repair", "the repair of", "repair of dna", "of dna damage.", "dna damage. the", "damage. the persistent", "the persistent ssdna", "persistent ssdna also", "ssdna also stimulates", "also stimulates recruitment", "stimulates recruitment of", "recruitment of the", "of the rfc", "the rfc like", "rfc like rad17", "like rad17 rfc2", "rad17 rfc2 5", "rfc2 5 alternative", "5 alternative clamp", "alternative clamp loading", "clamp loading complex", "complex which", "which subsequently loads", "subsequently loads the", "loads the rad9", "the rad9 hus1", "rad9 hus1 rad1", "hus1 rad1 complex", "rad1 complex onto", "complex onto the", "onto the dna.", "the dna. the", "dna. the latter", "the latter '9", "latter '9 1", "'9 1 1'", "1 1' complex", "1' complex serves", "complex serves to", "serves to facilitate", "to facilitate chk1", "facilitate chk1 binding", "chk1 binding to", "binding to the", "to the stalled", "the stalled replication", "stalled replication fork", "fork where", "where chk1 is", "chk1 is phosphorylated", "is phosphorylated by", "phosphorylated by atr", "by atr and", "atr and thereby", "and thereby activated.", "thereby activated. upon", "activated. upon activation", "activation chk1", "chk1 can phosphorylate", "can phosphorylate additional", "phosphorylate additional substrates", "additional substrates including", "substrates including the", "including the cdc25", "the cdc25 family", "cdc25 family of", "family of phosphatases", "phosphatases cdc25a", "cdc25a cdc25b", "and cdc25c .", "cdc25c . these", ". these enzymes", "these enzymes catalyze", "enzymes catalyze the", "catalyze the removal", "the removal of", "removal of inhibitory", "of inhibitory phosphate", "inhibitory phosphate residues", "phosphate residues from", "residues from cyclin", "from cyclin dependent", "allowing their activation.", "their activation. in", "activation. in particular", "particular cdc25a", "cdc25a primarily functions", "primarily functions at", "functions at the", "at the g1/s", "the g1/s transition", "g1/s transition to", "transition to dephosphorylate", "to dephosphorylate cdk2", "dephosphorylate cdk2 at", "cdk2 at thr", "at thr 14", "thr 14 and", "14 and tyr", "and tyr 15", "15 thus", "thus positively regulating", "positively regulating the", "regulating the cdk2", "the cdk2 cyclin", "cdk2 cyclin e", "cyclin e complex", "e complex for", "complex for s", "for s phase", "s phase entry.", "entry. cdc25a", "cdc25a also has", "also has mitotic", "has mitotic functions.", "mitotic functions. phosphorylation", "functions. phosphorylation of", "phosphorylation of cdc25a", "of cdc25a at", "cdc25a at ser125", "at ser125 by", "ser125 by chk1", "by chk1 leads", "chk1 leads to", "leads to cdc25a", "to cdc25a ubiquitination", "cdc25a ubiquitination and", "ubiquitination and degradation", "degradation thus", "thus inhibiting dna", "inhibiting dna replication", "dna replication origin", "replication origin firing.", "origin firing. in", "firing. in contrast", "contrast cdc25b", "cdc25b and cdc25c", "and cdc25c regulate", "cdc25c regulate the", "regulate the onset", "the onset of", "onset of mitosis", "of mitosis through", "mitosis through dephosphorylation", "through dephosphorylation and", "dephosphorylation and activation", "and activation of", "activation of cdk1", "of cdk1 cyclin", "cdk1 cyclin b", "cyclin b complexes.", "b complexes. in", "complexes. in response", "stress chk1", "chk1 phosphorylates cdc25b", "phosphorylates cdc25b and", "and cdc25c leading", "cdc25c leading to", "leading to cdc25b/c", "to cdc25b/c complex", "cdc25b/c complex formation", "complex formation with", "formation with 14", "with 14 3", "14 3 3", "3 3 proteins.", "3 proteins. as", "proteins. as these", "as these complexes", "these complexes are", "complexes are sequestered", "are sequestered in", "sequestered in the", "in the cytoplasm", "cytoplasm they", "they are unable", "are unable to", "unable to activate", "to activate the", "activate the nuclear", "the nuclear cdk1", "nuclear cdk1 cyclin", "cyclin b complex", "b complex for", "complex for mitotic", "for mitotic entry.

these", "mitotic entry.

these events", "entry.

these events are", "events are outlined", "are outlined in", "outlined in the", "in the figure.", "the figure. persistent", "figure. persistent single", "persistent single stranded", "single stranded dna", "stranded dna associated", "dna associated with", "associated with rpa", "with rpa binds", "rpa binds claspin", "claspin a", "a and", "atr:atrip b", "leading to claspin", "to claspin phosphorylation", "phosphorylation c", "c . in", ". in parallel", "parallel the", "the same single", "same single stranded", "single stranded dna:rpa", "stranded dna:rpa complex", "dna:rpa complex binds", "complex binds rad17:rfc", "rad17:rfc d", "enabling the loading", "the loading of", "loading of rad9:hus1:rad1", "rad9:hus1:rad1 9", "9 1 1", "1 complex", "onto the dna", "dna e", "e . the", ". the resulting", "the resulting complex", "resulting complex of", "complex of proteins", "of proteins can", "proteins can then", "can then repeatedly", "then repeatedly bind", "bind f", "f and", "phosphorylate g", "g chk1", "chk1 activating", "activating multiple copies", "multiple copies of", "copies of chk1.", "genotoxic stress caused by", "stress caused by dna", "caused by dna damage", "by dna damage or", "dna damage or stalled", "damage or stalled replication", "or stalled replication forks", "stalled replication forks can", "replication forks can lead", "forks can lead to", "can lead to genomic", "lead to genomic instability.", "to genomic instability. to", "genomic instability. to guard", "instability. to guard against", "to guard against such", "guard against such instability", "such instability genotoxically", "instability genotoxically stressed", "genotoxically stressed cells activate", "stressed cells activate checkpoint", "cells activate checkpoint factors", "activate checkpoint factors that", "checkpoint factors that halt", "factors that halt or", "that halt or slow", "halt or slow cell", "or slow cell cycle", "slow cell cycle progression.", "cell cycle progression. among", "cycle progression. among the", "progression. among the pathways", "among the pathways affected", "the pathways affected are", "pathways affected are dna", "affected are dna replication", "are dna replication by", "dna replication by reduction", "replication by reduction of", "by reduction of replication", "reduction of replication origin", "of replication origin firing", "origin firing and", "firing and mitosis", "and mitosis by inhibiting", "mitosis by inhibiting activation", "by inhibiting activation of", "inhibiting activation of cyclin", "activation of cyclin dependent", "of cyclin dependent kinases", "dependent kinases cdks", "kinases cdks .", "cdks . a key", ". a key factor", "a key factor involved", "key factor involved in", "factor involved in the", "involved in the response", "in the response to", "the response to stalled", "response to stalled replication", "to stalled replication forks", "stalled replication forks is", "replication forks is the", "forks is the atm", "the atm and", "atm and rad3", "rad3 related atr", "kinase a member", "a member of the", "member of the phosphoinositide", "of the phosphoinositide 3", "the phosphoinositide 3 kinase", "phosphoinositide 3 kinase related", "3 kinase related kinase", "related kinase pikk", "pikk family. rather", "family. rather than responding", "rather than responding to", "than responding to particular", "responding to particular lesions", "to particular lesions in", "particular lesions in dna", "in dna atr", "dna atr and", "atr and its binding", "and its binding partner", "its binding partner atrip", "partner atrip atr", "atrip atr interacting", "interacting protein sense", "protein sense replication", "sense replication fork stalling", "replication fork stalling indirectly", "fork stalling indirectly by", "stalling indirectly by associating", "indirectly by associating with", "by associating with persistent", "associating with persistent ssdna", "with persistent ssdna bound", "persistent ssdna bound by", "ssdna bound by rpa.", "bound by rpa. these", "by rpa. these structures", "rpa. these structures would", "these structures would be", "structures would be formed", "be formed for", "formed for example", "for example by", "example by dissociation", "by dissociation of the", "dissociation of the replicative", "of the replicative helicase", "the replicative helicase from", "replicative helicase from the", "helicase from the leading", "from the leading or", "the leading or lagging", "leading or lagging strand", "or lagging strand dna", "lagging strand dna polymerase", "strand dna polymerase when", "dna polymerase when the", "polymerase when the polymerase", "when the polymerase encounters", "the polymerase encounters a", "polymerase encounters a dna", "encounters a dna lesion", "a dna lesion that", "dna lesion that blocks", "lesion that blocks dna", "that blocks dna synthesis.", "blocks dna synthesis. along", "dna synthesis. along with", "along with phosphorylating", "with phosphorylating the", "phosphorylating the downstream transducer", "the downstream transducer kinase", "downstream transducer kinase chk1", "transducer kinase chk1 and", "kinase chk1 and the", "chk1 and the tumor", "and the tumor suppressor", "the tumor suppressor p53", "suppressor p53 activated", "p53 activated atr", "activated atr modifies numerous", "atr modifies numerous factors", "modifies numerous factors that", "numerous factors that regulate", "factors that regulate cell", "that regulate cell cycle", "regulate cell cycle progression", "cell cycle progression or", "cycle progression or the", "progression or the repair", "or the repair of", "the repair of dna", "repair of dna damage.", "of dna damage. the", "dna damage. the persistent", "damage. the persistent ssdna", "the persistent ssdna also", "persistent ssdna also stimulates", "ssdna also stimulates recruitment", "also stimulates recruitment of", "stimulates recruitment of the", "recruitment of the rfc", "of the rfc like", "the rfc like rad17", "rfc like rad17 rfc2", "like rad17 rfc2 5", "rad17 rfc2 5 alternative", "rfc2 5 alternative clamp", "5 alternative clamp loading", "alternative clamp loading complex", "loading complex which", "complex which subsequently", "which subsequently loads the", "subsequently loads the rad9", "loads the rad9 hus1", "the rad9 hus1 rad1", "rad9 hus1 rad1 complex", "hus1 rad1 complex onto", "rad1 complex onto the", "complex onto the dna.", "onto the dna. the", "the dna. the latter", "dna. the latter '9", "the latter '9 1", "latter '9 1 1'", "'9 1 1' complex", "1 1' complex serves", "1' complex serves to", "complex serves to facilitate", "serves to facilitate chk1", "to facilitate chk1 binding", "facilitate chk1 binding to", "chk1 binding to the", "binding to the stalled", "to the stalled replication", "the stalled replication fork", "replication fork where", "fork where chk1", "where chk1 is phosphorylated", "chk1 is phosphorylated by", "is phosphorylated by atr", "phosphorylated by atr and", "by atr and thereby", "atr and thereby activated.", "and thereby activated. upon", "thereby activated. upon activation", "upon activation chk1", "activation chk1 can", "chk1 can phosphorylate additional", "can phosphorylate additional substrates", "phosphorylate additional substrates including", "additional substrates including the", "substrates including the cdc25", "including the cdc25 family", "the cdc25 family of", "cdc25 family of phosphatases", "of phosphatases cdc25a", "and cdc25c . these", "cdc25c . these enzymes", ". these enzymes catalyze", "these enzymes catalyze the", "enzymes catalyze the removal", "catalyze the removal of", "the removal of inhibitory", "removal of inhibitory phosphate", "of inhibitory phosphate residues", "inhibitory phosphate residues from", "phosphate residues from cyclin", "residues from cyclin dependent", "from cyclin dependent kinases", "cdks allowing", "allowing their activation. in", "their activation. in particular", "in particular cdc25a", "particular cdc25a primarily", "cdc25a primarily functions at", "primarily functions at the", "functions at the g1/s", "at the g1/s transition", "the g1/s transition to", "g1/s transition to dephosphorylate", "transition to dephosphorylate cdk2", "to dephosphorylate cdk2 at", "dephosphorylate cdk2 at thr", "cdk2 at thr 14", "at thr 14 and", "thr 14 and tyr", "14 and tyr 15", "tyr 15 thus", "15 thus positively", "thus positively regulating the", "positively regulating the cdk2", "regulating the cdk2 cyclin", "the cdk2 cyclin e", "cdk2 cyclin e complex", "cyclin e complex for", "e complex for s", "complex for s phase", "for s phase entry.", "phase entry. cdc25a", "entry. cdc25a also", "cdc25a also has mitotic", "also has mitotic functions.", "has mitotic functions. phosphorylation", "mitotic functions. phosphorylation of", "functions. phosphorylation of cdc25a", "phosphorylation of cdc25a at", "of cdc25a at ser125", "cdc25a at ser125 by", "at ser125 by chk1", "ser125 by chk1 leads", "by chk1 leads to", "chk1 leads to cdc25a", "leads to cdc25a ubiquitination", "to cdc25a ubiquitination and", "cdc25a ubiquitination and degradation", "and degradation thus", "degradation thus inhibiting", "thus inhibiting dna replication", "inhibiting dna replication origin", "dna replication origin firing.", "replication origin firing. in", "origin firing. in contrast", "in contrast cdc25b", "contrast cdc25b and", "cdc25b and cdc25c regulate", "and cdc25c regulate the", "cdc25c regulate the onset", "regulate the onset of", "the onset of mitosis", "onset of mitosis through", "of mitosis through dephosphorylation", "mitosis through dephosphorylation and", "through dephosphorylation and activation", "dephosphorylation and activation of", "and activation of cdk1", "activation of cdk1 cyclin", "of cdk1 cyclin b", "cdk1 cyclin b complexes.", "cyclin b complexes. in", "b complexes. in response", "complexes. in response to", "replication stress chk1", "stress chk1 phosphorylates", "chk1 phosphorylates cdc25b and", "phosphorylates cdc25b and cdc25c", "cdc25b and cdc25c leading", "and cdc25c leading to", "cdc25c leading to cdc25b/c", "leading to cdc25b/c complex", "to cdc25b/c complex formation", "cdc25b/c complex formation with", "complex formation with 14", "formation with 14 3", "with 14 3 3", "14 3 3 proteins.", "3 3 proteins. as", "3 proteins. as these", "proteins. as these complexes", "as these complexes are", "these complexes are sequestered", "complexes are sequestered in", "are sequestered in the", "sequestered in the cytoplasm", "the cytoplasm they", "cytoplasm they are", "they are unable to", "are unable to activate", "unable to activate the", "to activate the nuclear", "activate the nuclear cdk1", "the nuclear cdk1 cyclin", "nuclear cdk1 cyclin b", "cdk1 cyclin b complex", "cyclin b complex for", "b complex for mitotic", "complex for mitotic entry.

these", "for mitotic entry.

these events", "mitotic entry.

these events are", "entry.

these events are outlined", "events are outlined in", "are outlined in the", "outlined in the figure.", "in the figure. persistent", "the figure. persistent single", "figure. persistent single stranded", "persistent single stranded dna", "single stranded dna associated", "stranded dna associated with", "dna associated with rpa", "associated with rpa binds", "with rpa binds claspin", "binds claspin a", "a and atr:atrip", "and atr:atrip b", "b leading", "leading to claspin phosphorylation", "claspin phosphorylation c", "phosphorylation c .", "c . in parallel", "in parallel the", "parallel the same", "the same single stranded", "same single stranded dna:rpa", "single stranded dna:rpa complex", "stranded dna:rpa complex binds", "dna:rpa complex binds rad17:rfc", "binds rad17:rfc d", "d enabling", "enabling the loading of", "the loading of rad9:hus1:rad1", "of rad9:hus1:rad1 9", "rad9:hus1:rad1 9 1", "1 1 complex", "1 complex onto", "complex onto the dna", "the dna e", "dna e .", "e . the resulting", ". the resulting complex", "the resulting complex of", "resulting complex of proteins", "complex of proteins can", "of proteins can then", "proteins can then repeatedly", "can then repeatedly bind", "repeatedly bind f", "f and phosphorylate", "and phosphorylate g", "chk1 activating multiple", "activating multiple copies of", "multiple copies of chk1.", "genotoxic stress caused by dna", "stress caused by dna damage", "caused by dna damage or", "by dna damage or stalled", "dna damage or stalled replication", "damage or stalled replication forks", "or stalled replication forks can", "stalled replication forks can lead", "replication forks can lead to", "forks can lead to genomic", "can lead to genomic instability.", "lead to genomic instability. to", "to genomic instability. to guard", "genomic instability. to guard against", "instability. to guard against such", "to guard against such instability", "against such instability genotoxically", "such instability genotoxically stressed", "instability genotoxically stressed cells", "genotoxically stressed cells activate checkpoint", "stressed cells activate checkpoint factors", "cells activate checkpoint factors that", "activate checkpoint factors that halt", "checkpoint factors that halt or", "factors that halt or slow", "that halt or slow cell", "halt or slow cell cycle", "or slow cell cycle progression.", "slow cell cycle progression. among", "cell cycle progression. among the", "cycle progression. among the pathways", "progression. among the pathways affected", "among the pathways affected are", "the pathways affected are dna", "pathways affected are dna replication", "affected are dna replication by", "are dna replication by reduction", "dna replication by reduction of", "replication by reduction of replication", "by reduction of replication origin", "reduction of replication origin firing", "replication origin firing and", "origin firing and mitosis", "firing and mitosis by", "and mitosis by inhibiting activation", "mitosis by inhibiting activation of", "by inhibiting activation of cyclin", "inhibiting activation of cyclin dependent", "activation of cyclin dependent kinases", "cyclin dependent kinases cdks", "dependent kinases cdks .", "kinases cdks . a", "cdks . a key factor", ". a key factor involved", "a key factor involved in", "key factor involved in the", "factor involved in the response", "involved in the response to", "in the response to stalled", "the response to stalled replication", "response to stalled replication forks", "to stalled replication forks is", "stalled replication forks is the", "replication forks is the atm", "is the atm and", "the atm and rad3", "atm and rad3 related", "and rad3 related atr", "related atr kinase", "atr kinase a", "kinase a member of", "a member of the phosphoinositide", "member of the phosphoinositide 3", "of the phosphoinositide 3 kinase", "the phosphoinositide 3 kinase related", "phosphoinositide 3 kinase related kinase", "kinase related kinase pikk", "kinase pikk family.", "pikk family. rather than", "family. rather than responding to", "rather than responding to particular", "than responding to particular lesions", "responding to particular lesions in", "to particular lesions in dna", "lesions in dna atr", "in dna atr and", "dna atr and its", "atr and its binding partner", "and its binding partner atrip", "binding partner atrip atr", "partner atrip atr interacting", "atrip atr interacting protein", "atr interacting protein sense", "interacting protein sense replication", "protein sense replication fork", "sense replication fork stalling indirectly", "replication fork stalling indirectly by", "fork stalling indirectly by associating", "stalling indirectly by associating with", "indirectly by associating with persistent", "by associating with persistent ssdna", "associating with persistent ssdna bound", "with persistent ssdna bound by", "persistent ssdna bound by rpa.", "ssdna bound by rpa. these", "bound by rpa. these structures", "by rpa. these structures would", "rpa. these structures would be", "these structures would be formed", "would be formed for", "be formed for example", "for example by dissociation", "example by dissociation of", "by dissociation of the replicative", "dissociation of the replicative helicase", "of the replicative helicase from", "the replicative helicase from the", "replicative helicase from the leading", "helicase from the leading or", "from the leading or lagging", "the leading or lagging strand", "leading or lagging strand dna", "or lagging strand dna polymerase", "lagging strand dna polymerase when", "strand dna polymerase when the", "dna polymerase when the polymerase", "polymerase when the polymerase encounters", "when the polymerase encounters a", "the polymerase encounters a dna", "polymerase encounters a dna lesion", "encounters a dna lesion that", "a dna lesion that blocks", "dna lesion that blocks dna", "lesion that blocks dna synthesis.", "that blocks dna synthesis. along", "blocks dna synthesis. along with", "synthesis. along with phosphorylating", "along with phosphorylating the", "with phosphorylating the downstream", "phosphorylating the downstream transducer kinase", "the downstream transducer kinase chk1", "downstream transducer kinase chk1 and", "transducer kinase chk1 and the", "kinase chk1 and the tumor", "chk1 and the tumor suppressor", "and the tumor suppressor p53", "tumor suppressor p53 activated", "suppressor p53 activated atr", "p53 activated atr modifies", "activated atr modifies numerous factors", "atr modifies numerous factors that", "modifies numerous factors that regulate", "numerous factors that regulate cell", "factors that regulate cell cycle", "that regulate cell cycle progression", "regulate cell cycle progression or", "cell cycle progression or the", "cycle progression or the repair", "progression or the repair of", "or the repair of dna", "the repair of dna damage.", "repair of dna damage. the", "of dna damage. the persistent", "dna damage. the persistent ssdna", "damage. the persistent ssdna also", "the persistent ssdna also stimulates", "persistent ssdna also stimulates recruitment", "ssdna also stimulates recruitment of", "also stimulates recruitment of the", "stimulates recruitment of the rfc", "recruitment of the rfc like", "of the rfc like rad17", "the rfc like rad17 rfc2", "rfc like rad17 rfc2 5", "like rad17 rfc2 5 alternative", "rad17 rfc2 5 alternative clamp", "rfc2 5 alternative clamp loading", "5 alternative clamp loading complex", "clamp loading complex which", "loading complex which subsequently", "complex which subsequently loads", "which subsequently loads the rad9", "subsequently loads the rad9 hus1", "loads the rad9 hus1 rad1", "the rad9 hus1 rad1 complex", "rad9 hus1 rad1 complex onto", "hus1 rad1 complex onto the", "rad1 complex onto the dna.", "complex onto the dna. the", "onto the dna. the latter", "the dna. the latter '9", "dna. the latter '9 1", "the latter '9 1 1'", "latter '9 1 1' complex", "'9 1 1' complex serves", "1 1' complex serves to", "1' complex serves to facilitate", "complex serves to facilitate chk1", "serves to facilitate chk1 binding", "to facilitate chk1 binding to", "facilitate chk1 binding to the", "chk1 binding to the stalled", "binding to the stalled replication", "to the stalled replication fork", "stalled replication fork where", "replication fork where chk1", "fork where chk1 is", "where chk1 is phosphorylated by", "chk1 is phosphorylated by atr", "is phosphorylated by atr and", "phosphorylated by atr and thereby", "by atr and thereby activated.", "atr and thereby activated. upon", "and thereby activated. upon activation", "activated. upon activation chk1", "upon activation chk1 can", "activation chk1 can phosphorylate", "chk1 can phosphorylate additional substrates", "can phosphorylate additional substrates including", "phosphorylate additional substrates including the", "additional substrates including the cdc25", "substrates including the cdc25 family", "including the cdc25 family of", "the cdc25 family of phosphatases", "family of phosphatases cdc25a", "phosphatases cdc25a cdc25b", "cdc25a cdc25b and", "cdc25b and cdc25c .", "and cdc25c . these enzymes", "cdc25c . these enzymes catalyze", ". these enzymes catalyze the", "these enzymes catalyze the removal", "enzymes catalyze the removal of", "catalyze the removal of inhibitory", "the removal of inhibitory phosphate", "removal of inhibitory phosphate residues", "of inhibitory phosphate residues from", "inhibitory phosphate residues from cyclin", "phosphate residues from cyclin dependent", "residues from cyclin dependent kinases", "cdks allowing their", "allowing their activation. in particular", "activation. in particular cdc25a", "in particular cdc25a primarily", "particular cdc25a primarily functions", "cdc25a primarily functions at the", "primarily functions at the g1/s", "functions at the g1/s transition", "at the g1/s transition to", "the g1/s transition to dephosphorylate", "g1/s transition to dephosphorylate cdk2", "transition to dephosphorylate cdk2 at", "to dephosphorylate cdk2 at thr", "dephosphorylate cdk2 at thr 14", "cdk2 at thr 14 and", "at thr 14 and tyr", "thr 14 and tyr 15", "and tyr 15 thus", "tyr 15 thus positively", "15 thus positively regulating", "thus positively regulating the cdk2", "positively regulating the cdk2 cyclin", "regulating the cdk2 cyclin e", "the cdk2 cyclin e complex", "cdk2 cyclin e complex for", "cyclin e complex for s", "e complex for s phase", "complex for s phase entry.", "s phase entry. cdc25a", "phase entry. cdc25a also", "entry. cdc25a also has", "cdc25a also has mitotic functions.", "also has mitotic functions. phosphorylation", "has mitotic functions. phosphorylation of", "mitotic functions. phosphorylation of cdc25a", "functions. phosphorylation of cdc25a at", "phosphorylation of cdc25a at ser125", "of cdc25a at ser125 by", "cdc25a at ser125 by chk1", "at ser125 by chk1 leads", "ser125 by chk1 leads to", "by chk1 leads to cdc25a", "chk1 leads to cdc25a ubiquitination", "leads to cdc25a ubiquitination and", "to cdc25a ubiquitination and degradation", "ubiquitination and degradation thus", "and degradation thus inhibiting", "degradation thus inhibiting dna", "thus inhibiting dna replication origin", "inhibiting dna replication origin firing.", "dna replication origin firing. in", "replication origin firing. in contrast", "firing. in contrast cdc25b", "in contrast cdc25b and", "contrast cdc25b and cdc25c", "cdc25b and cdc25c regulate the", "and cdc25c regulate the onset", "cdc25c regulate the onset of", "regulate the onset of mitosis", "the onset of mitosis through", "onset of mitosis through dephosphorylation", "of mitosis through dephosphorylation and", "mitosis through dephosphorylation and activation", "through dephosphorylation and activation of", "dephosphorylation and activation of cdk1", "and activation of cdk1 cyclin", "activation of cdk1 cyclin b", "of cdk1 cyclin b complexes.", "cdk1 cyclin b complexes. in", "cyclin b complexes. in response", "b complexes. in response to", "complexes. in response to replication", "to replication stress chk1", "replication stress chk1 phosphorylates", "stress chk1 phosphorylates cdc25b", "chk1 phosphorylates cdc25b and cdc25c", "phosphorylates cdc25b and cdc25c leading", "cdc25b and cdc25c leading to", "and cdc25c leading to cdc25b/c", "cdc25c leading to cdc25b/c complex", "leading to cdc25b/c complex formation", "to cdc25b/c complex formation with", "cdc25b/c complex formation with 14", "complex formation with 14 3", "formation with 14 3 3", "with 14 3 3 proteins.", "14 3 3 proteins. as", "3 3 proteins. as these", "3 proteins. as these complexes", "proteins. as these complexes are", "as these complexes are sequestered", "these complexes are sequestered in", "complexes are sequestered in the", "are sequestered in the cytoplasm", "in the cytoplasm they", "the cytoplasm they are", "cytoplasm they are unable", "they are unable to activate", "are unable to activate the", "unable to activate the nuclear", "to activate the nuclear cdk1", "activate the nuclear cdk1 cyclin", "the nuclear cdk1 cyclin b", "nuclear cdk1 cyclin b complex", "cdk1 cyclin b complex for", "cyclin b complex for mitotic", "b complex for mitotic entry.

these", "complex for mitotic entry.

these events", "for mitotic entry.

these events are", "mitotic entry.

these events are outlined", "entry.

these events are outlined in", "events are outlined in the", "are outlined in the figure.", "outlined in the figure. persistent", "in the figure. persistent single", "the figure. persistent single stranded", "figure. persistent single stranded dna", "persistent single stranded dna associated", "single stranded dna associated with", "stranded dna associated with rpa", "dna associated with rpa binds", "associated with rpa binds claspin", "rpa binds claspin a", "claspin a and", "b leading to", "to claspin phosphorylation c", "claspin phosphorylation c .", "phosphorylation c . in", ". in parallel the", "in parallel the same", "parallel the same single", "the same single stranded dna:rpa", "same single stranded dna:rpa complex", "single stranded dna:rpa complex binds", "stranded dna:rpa complex binds rad17:rfc", "complex binds rad17:rfc d", "d enabling the", "enabling the loading of rad9:hus1:rad1", "loading of rad9:hus1:rad1 9", "of rad9:hus1:rad1 9 1", "rad9:hus1:rad1 9 1 1", "9 1 1 complex", "1 1 complex onto", "1 complex onto the", "onto the dna e", "the dna e .", "dna e . the", "e . the resulting complex", ". the resulting complex of", "the resulting complex of proteins", "resulting complex of proteins can", "complex of proteins can then", "of proteins can then repeatedly", "proteins can then repeatedly bind", "then repeatedly bind f", "bind f and", "phosphorylate g chk1", "g chk1 activating", "chk1 activating multiple copies", "activating multiple copies of chk1." ] }, { "record_id": "GLY_000594_1_127", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "176407", "r hsa", "hsa 176407", "r hsa 176407" ] }, { "record_id": "GLY_000594_1_127", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "conversion from", "from apc/c:cdc20", "apc/c:cdc20 to", "to apc/c:cdh1", "apc/c:cdh1 in", "in late", "late anaphase", "conversion from apc/c:cdc20", "from apc/c:cdc20 to", "apc/c:cdc20 to 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sister chromatid separation", "sister chromatid separation and", "chromatid separation and the", "separation and the proper", "and the proper timing", "the proper timing of", "proper timing of exit", "timing of exit from", "of exit from mitosis", "from mitosis see", "mitosis see zachariae", "see zachariae and nasmyth", "and nasmyth 1999", "nasmyth 1999 .", "1999 . cdc20", ". cdc20 is", "is degraded late", "degraded late in", "in mitosis reviewed", "mitosis reviewed in", "reviewed in owens and", "in owens and hoyt", "and hoyt 2005", "following phosphorylation of the apc/c", "phosphorylation of the apc/c core", "of the apc/c core subunits", "the apc/c core subunits by", "apc/c core subunits by mitotic", "core subunits by mitotic kinases", "by mitotic kinases the", "kinases the activating", "activating protein cdc20 is", "protein cdc20 is recruited", "cdc20 is recruited to the", "is recruited to the apc", "recruited to the apc and", "to the apc and promotes", "the apc and promotes the", 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degradation of these proteins", "degradation of these proteins is", "of these proteins is essential", "proteins is essential for", "is essential for sister", "essential for sister chromatid", "for sister chromatid separation and", "sister chromatid separation and the", "chromatid separation and the proper", "separation and the proper timing", "and the proper timing of", "the proper timing of exit", "proper timing of exit from", "timing of exit from mitosis", "exit from mitosis see", "from mitosis see zachariae", "mitosis see zachariae and", "zachariae and nasmyth 1999", "and nasmyth 1999 .", "1999 . cdc20 is", ". cdc20 is degraded", "cdc20 is degraded late", "is degraded late in", "degraded late in mitosis", "late in mitosis reviewed", "in mitosis reviewed in", "mitosis reviewed in owens", "reviewed in owens and hoyt", "owens and hoyt 2005" ] }, { "record_id": "GLY_000594_1_130", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "176412", "r hsa", "hsa 176412", "r hsa 176412" ] }, { "record_id": "GLY_000594_1_130", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phosphorylation of", "of the", "the apc/c", "phosphorylation of the", "of the apc/c", "phosphorylation of the apc/c", "of apc", "apc subunits", "subunits is", "is required", "required for", "for cdc20", "cdc20 mediated", "mediated activation", "activation by", "by of", "apc/c at", "at the", "the metaphase", "metaphase anaphase", "anaphase transition", "kramer et", "et al.", "2000 .", ". while", "while the", "the kinases", "kinases responsible", "responsible for", "for phosphorylation", "phosphorylation in", "in vivo", "vivo have", "have not", "not been", "been determined", "determined with", "with certainty", "both plk1", "plk1 and", "and cyclin", "cyclin b:cdc2", "b:cdc2 have", "have been", "been implicated", "implicated in", "in this", "this process.", "phosphorylation of apc", "of apc subunits", "apc subunits is", "subunits is required", "is required for", "required for cdc20", "for cdc20 mediated", "cdc20 mediated activation", "mediated activation by", "activation by of", "by of the", "the apc/c at", "apc/c at the", "at the metaphase", "the metaphase anaphase", "metaphase anaphase transition", "transition kramer", "kramer et al.", "al. 2000", "2000 . while", ". while the", "while the kinases", "the kinases responsible", "kinases responsible for", "responsible for phosphorylation", "for phosphorylation in", "phosphorylation in vivo", "in vivo have", "vivo have not", "have not been", "not been determined", "been determined with", "determined with certainty", "both plk1 and", "plk1 and cyclin", "and cyclin b:cdc2", "cyclin b:cdc2 have", "b:cdc2 have been", "have been implicated", "been implicated in", "implicated in this", "in this process.", "phosphorylation of apc subunits", "of apc subunits is", "apc subunits is required", "subunits is required for", "is required for cdc20", "required for cdc20 mediated", "for cdc20 mediated activation", "cdc20 mediated activation by", "mediated activation by of", "activation by of the", "by of the apc/c", "of the apc/c at", "the apc/c at the", "apc/c at the metaphase", "at the metaphase anaphase", "the metaphase anaphase transition", "anaphase transition kramer", "transition kramer et", "et al. 2000", "al. 2000 .", "2000 . while the", ". while the kinases", "while the kinases responsible", "the kinases responsible for", "kinases responsible for phosphorylation", "responsible for phosphorylation in", "for phosphorylation in vivo", "phosphorylation in vivo have", "in vivo have not", "vivo have not been", "have not been determined", "not been determined with", "been determined with certainty", "certainty both", "both plk1 and cyclin", "plk1 and cyclin b:cdc2", "and cyclin b:cdc2 have", "cyclin b:cdc2 have been", "b:cdc2 have been implicated", "have been implicated in", "been implicated in this", "implicated in this process.", "phosphorylation of apc subunits is", "of apc subunits is required", "apc subunits is required for", "subunits is required for cdc20", "is required for cdc20 mediated", "required for cdc20 mediated activation", "for cdc20 mediated activation by", "cdc20 mediated activation by of", "mediated activation by of the", "activation by of the apc/c", "by of the apc/c at", "of the apc/c at the", "the apc/c at the metaphase", "apc/c at the metaphase anaphase", "at the metaphase anaphase transition", "metaphase anaphase transition kramer", "anaphase transition kramer et", "transition kramer et al.", "kramer et al. 2000", "et al. 2000 .", "al. 2000 . while", "2000 . while the kinases", ". while the kinases responsible", "while the kinases responsible for", "the kinases responsible for phosphorylation", "kinases responsible for phosphorylation in", "responsible for phosphorylation in vivo", "for phosphorylation in vivo have", "phosphorylation in vivo have not", "in vivo have not been", "vivo have not been determined", "have not been determined with", "not been determined with certainty", "with certainty both", "certainty both plk1", "both plk1 and cyclin b:cdc2", "plk1 and cyclin b:cdc2 have", "and cyclin b:cdc2 have been", "cyclin b:cdc2 have been implicated", "b:cdc2 have been implicated in", "have been implicated in this", "been implicated in this process." ] }, { "record_id": "GLY_000594_1_131", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "177929", "r hsa", "hsa 177929", "r hsa 177929" ] }, { "record_id": "GLY_000594_1_131", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by egfr", "signaling by egfr", "the epidermal", "epidermal growth", "growth factor", "factor receptor", "is one", "one member", "member of", "of the", "the erbb", "erbb family", "family of", "of transmembrane", "transmembrane glycoprotein", "glycoprotein tyrosine", "tyrosine receptor", "receptor kinases", "rtk .", ". binding", "binding of", "of egfr", "egfr to", "to its", "its ligands", "ligands induces", "induces conformational", "conformational change", "change that", "that unmasks", "unmasks the", "the dimerization", "dimerization interface", "interface in", "in the", "the extracellular", "extracellular domain", "domain of", "leading to", "to receptor", "receptor homo", "or heterodimerization", "heterodimerization at", "at the", "the cell", "cell surface.", "surface. dimerization", "dimerization of", "extracellular regions", "regions of", "egfr triggers", "triggers additional", "additional conformational", "change of", "the cytoplasmic", "cytoplasmic egfr", "egfr regions", "enabling the", "the kinase", "kinase domains", "domains of", "of two", "two egfr", "egfr molecules", "molecules to", "to achieve", "achieve the", "the catalytically", "catalytically active", "active conformation.", "conformation. ligand", "ligand activated", "activated egfr", "egfr dimers", "dimers trans", "trans autophosphorylate", "autophosphorylate on", "on tyrosine", "tyrosine residues", "residues in", "cytoplasmic tail", "tail of", "the receptor.", "receptor. phosphorylated", "phosphorylated tyrosines", "tyrosines serve", "serve as", "as binding", "binding sites", "sites for", "for the", "the recruitment", "recruitment of", "of signal", "signal transducers", "transducers and", "and activators", "activators of", "of intracellular", "intracellular substrates", "which then", "then stimulate", "stimulate intracellular", "intracellular signal", "signal transduction", "transduction cascades", "cascades that", "that are", "are involved", "involved in", "in regulating", "regulating cellular", "cellular proliferation", "and survival.", "survival. recruitment", "of complexes", "complexes containing", "containing grb2", "grb2 and", "and sos1", "sos1 to", "to phosphorylated", "phosphorylated egfr", "dimers either", "either directly", "through phosphotyrosine", "phosphotyrosine residues", "residues that", "that serve", "as grb2", "grb2 docking", "docking sites", "or indirectly", "through shc1", "shc1 recruitment", "promotes gdp", "gdp to", "to gtp", "gtp exchange", "exchange on", "on ras", "resulting in", "the activation", "activation of", "of raf/map", "raf/map kinase", "kinase cascade.", "cascade. binding", "complexes of", "of grb2", "and gab1", "gab1 to", "dimers leads", "leads to", "to formation", "formation of", "the active", "active pi3k", "pi3k complex", "conversion of", "of pip2", "pip2 into", "into pip3", "and activation", "of akt", "akt signaling.", "signaling. phospholipase", "phospholipase c", "c gamma1", "can also", "also be", "be recruited", "recruited directly", "through egfr", "egfr phosphotyrosine", "as plcg1", "plcg1 docking", "which leads", "to plcg1", "plcg1 phosphorylation", "phosphorylation by", "egfr and", "of dag", "dag and", "and ip3", "ip3 signaling.", "signaling. egfr", "egfr signaling", "signaling is", "is downregulated", "downregulated by", "by the", "the action", "action of", "of ubiquitin", "ubiquitin ligase", "ligase cbl.", "cbl. cbl", "cbl binds", "binds directly", "directly to", "to the", "the phosphorylated", "egfr dimer", "dimer through", "through the", "the phosphotyrosine", "phosphotyrosine y1069", "i.e. y1045", "y1045 in", "the mature", "mature protein", "the c", "c tail", "and after", "after cbl", "cbl is", "is phosphorylated", "phosphorylated by", "it becomes", "becomes active", "active and", "and ubiquitinates", "ubiquitinates phosphorylated", "targeting them", "them for", "for degradation.", "degradation. positive", "positive regulation", "regulation of", "by direct", "direct association", "association of", "egfr with", "with accessory", "accessory proteins", "proteins such", "such as", "as aamp", "aamp and", "and fam83b", "fam83b is", "is being", "being investigated.", "investigated. for", "for review", "review of", "please refer", "refer to", "to carpenter", "carpenter 1999", "wells 1999", "schlessinger 2002", "herbst 2004", "avraham and", "and yarden", "bartel et", "et al.", "al. 2016", "uribe et", "al. 2021", "keflee et", "al. 2022.", "the epidermal growth", "epidermal growth factor", "growth factor receptor", "receptor egfr", "egfr is", "is one member", "one member of", "member of the", "of the erbb", "the erbb family", "erbb family of", "family of transmembrane", "of transmembrane glycoprotein", "transmembrane glycoprotein tyrosine", "glycoprotein tyrosine receptor", "tyrosine receptor kinases", "kinases rtk", "rtk . binding", ". binding of", "binding of egfr", "of egfr to", "egfr to its", "to its ligands", "its ligands induces", "ligands induces conformational", "induces conformational change", "conformational change that", "change that unmasks", "that unmasks the", "unmasks the dimerization", "the dimerization interface", "dimerization interface in", "interface in the", "in the extracellular", "the extracellular domain", "extracellular domain of", "domain of egfr", "egfr leading", "leading to receptor", "to receptor homo", "homo or", "or heterodimerization at", "heterodimerization at the", "at the cell", "the cell surface.", "cell surface. dimerization", "surface. dimerization of", "dimerization of the", "of the extracellular", "the extracellular regions", "extracellular regions of", "regions of egfr", "of egfr triggers", "egfr triggers additional", "triggers additional conformational", "additional conformational change", "conformational change of", "change of the", "of the cytoplasmic", "the cytoplasmic egfr", "cytoplasmic egfr regions", "regions enabling", "enabling the kinase", "the kinase domains", "kinase domains of", "domains of two", "of two egfr", "two egfr molecules", "egfr molecules to", "molecules to achieve", "to achieve the", "achieve the catalytically", "the catalytically active", "catalytically active conformation.", "active conformation. ligand", "conformation. ligand activated", "ligand activated egfr", "activated egfr dimers", "egfr dimers trans", "dimers trans autophosphorylate", "trans autophosphorylate on", "autophosphorylate on tyrosine", "on tyrosine residues", "tyrosine residues in", "residues in the", "in the cytoplasmic", "the cytoplasmic tail", "cytoplasmic tail of", "tail of the", "of the receptor.", "the receptor. phosphorylated", "receptor. phosphorylated tyrosines", "phosphorylated tyrosines serve", "tyrosines serve as", "serve as binding", "as binding sites", "binding sites for", "sites for the", "for the recruitment", "the recruitment of", "recruitment of signal", "of signal transducers", "signal transducers and", "transducers and activators", "and activators of", "activators of intracellular", "of intracellular substrates", "substrates which", "which then stimulate", "then stimulate intracellular", "stimulate intracellular signal", "intracellular signal transduction", "signal transduction cascades", "transduction cascades that", "cascades that are", "that are involved", "are involved in", "involved in regulating", "in regulating cellular", "regulating cellular proliferation", "proliferation differentiation", "differentiation and", "and survival. recruitment", "survival. recruitment of", "recruitment of complexes", "of complexes containing", "complexes containing grb2", "containing grb2 and", "grb2 and sos1", "and sos1 to", "sos1 to phosphorylated", "to phosphorylated egfr", "phosphorylated egfr dimers", "egfr dimers either", "dimers either directly", "directly through", "through phosphotyrosine residues", "phosphotyrosine residues that", "residues that serve", "that serve as", "serve as grb2", "as grb2 docking", "grb2 docking sites", "sites or", "indirectly through", "through shc1 recruitment", "recruitment promotes", "promotes gdp to", "gdp to gtp", "to gtp exchange", "gtp exchange on", "exchange on ras", "ras resulting", "resulting in the", "in the activation", "the activation of", "activation of raf/map", "of raf/map kinase", "raf/map kinase cascade.", "kinase cascade. binding", "cascade. binding of", "binding of complexes", "of complexes of", "complexes of grb2", "of grb2 and", "grb2 and gab1", "and gab1 to", "gab1 to phosphorylated", "egfr dimers leads", "dimers leads to", "leads to formation", "to formation of", "formation of the", "of the active", "the active pi3k", "active pi3k complex", "complex conversion", "conversion of pip2", "of pip2 into", "pip2 into pip3", "pip3 and", "and activation of", "activation of akt", "of akt signaling.", "akt signaling. phospholipase", "signaling. phospholipase c", "phospholipase c gamma1", "gamma1 plcg1", "plcg1 can", "can also be", "also be recruited", "be recruited directly", "through egfr phosphotyrosine", "egfr phosphotyrosine residues", "serve as plcg1", "as plcg1 docking", "plcg1 docking sites", "sites which", "which leads to", "leads to plcg1", "to plcg1 phosphorylation", "plcg1 phosphorylation by", "phosphorylation by egfr", "by egfr and", "egfr and activation", "activation of dag", "of dag and", "dag and ip3", "and ip3 signaling.", "ip3 signaling. egfr", "signaling. egfr signaling", "egfr signaling is", "signaling is downregulated", "is downregulated by", "downregulated by the", "by the action", "the action of", "action of ubiquitin", "of ubiquitin ligase", "ubiquitin ligase cbl.", "ligase cbl. cbl", "cbl. cbl binds", "cbl binds directly", "binds directly to", "directly to the", "to the phosphorylated", "the phosphorylated egfr", "phosphorylated egfr dimer", "egfr dimer through", "dimer through the", "through the phosphotyrosine", "the phosphotyrosine y1069", "y1069 i.e.", "i.e. y1045 in", "y1045 in the", "in the mature", "the mature protein", "protein in", "in the c", "the c tail", "c tail of", "tail of egfr", "and after cbl", "after cbl is", "cbl is phosphorylated", "is phosphorylated by", "phosphorylated by egfr", "egfr it", "it becomes active", "becomes active and", "active and ubiquitinates", "and ubiquitinates phosphorylated", "ubiquitinates phosphorylated egfr", "dimers targeting", "targeting them for", "them for degradation.", "for degradation. positive", "degradation. positive regulation", "positive regulation of", "regulation of egfr", "of egfr signaling", "egfr signaling by", "signaling by direct", "by direct association", "direct association of", "association of egfr", "of egfr with", "egfr with accessory", "with accessory proteins", "accessory proteins such", "proteins such as", "such as aamp", "as aamp and", "aamp and fam83b", "and fam83b is", "fam83b is being", "is being investigated.", "being investigated. for", "investigated. for review", "for review of", "review of egfr", "signaling please", "please refer to", "refer to carpenter", "to carpenter 1999", "1999 wells", "1999 schlessinger", "2002 herbst", "2004 avraham", "avraham and yarden", "yarden 2011", "2011 bartel", "bartel et al.", "et al. 2016", "2016 uribe", "uribe et al.", "et al. 2021", "2021 keflee", "keflee et al.", "et al. 2022.", "the epidermal growth factor", "epidermal growth factor receptor", "factor receptor egfr", "egfr is one", "is one member of", "one member of the", "member of the erbb", "of the erbb family", "the erbb family of", "erbb family of transmembrane", "family of transmembrane glycoprotein", "of transmembrane glycoprotein tyrosine", "transmembrane glycoprotein tyrosine receptor", "glycoprotein tyrosine receptor kinases", "receptor kinases rtk", "kinases rtk .", "rtk . binding of", ". binding of egfr", "binding of egfr to", "of egfr to its", "egfr to its ligands", "to its ligands induces", "its ligands induces conformational", "ligands induces conformational change", "induces conformational change that", "conformational change that unmasks", "change that unmasks the", "that unmasks the dimerization", "unmasks the dimerization interface", "the dimerization interface in", "dimerization interface in the", "interface in the extracellular", "in the extracellular domain", "the extracellular domain of", "extracellular domain of egfr", "of egfr leading", "egfr leading to", "leading to receptor homo", "receptor homo or", "homo or heterodimerization", "or heterodimerization at the", "heterodimerization at the cell", "at the cell surface.", "the cell surface. dimerization", "cell surface. dimerization of", "surface. dimerization of the", "dimerization of the extracellular", "of the extracellular regions", "the extracellular regions of", "extracellular regions of egfr", "regions of egfr triggers", "of egfr triggers additional", "egfr triggers additional conformational", "triggers additional conformational change", "additional conformational change of", "conformational change of the", "change of the cytoplasmic", "of the cytoplasmic egfr", "the cytoplasmic egfr regions", "egfr regions enabling", "regions enabling the", "enabling the kinase domains", "the kinase domains of", "kinase domains of two", "domains of two egfr", "of two egfr molecules", "two egfr molecules to", "egfr molecules to achieve", "molecules to achieve the", "to achieve the catalytically", "achieve the catalytically active", "the catalytically active conformation.", "catalytically active conformation. ligand", "active conformation. ligand activated", "conformation. ligand activated egfr", "ligand activated egfr dimers", "activated egfr dimers trans", "egfr dimers trans autophosphorylate", "dimers trans autophosphorylate on", "trans autophosphorylate on tyrosine", "autophosphorylate on tyrosine residues", "on tyrosine residues in", "tyrosine residues in the", "residues in the cytoplasmic", "in the cytoplasmic tail", "the cytoplasmic tail of", "cytoplasmic tail of the", "tail of the receptor.", "of the receptor. phosphorylated", "the receptor. phosphorylated tyrosines", "receptor. phosphorylated tyrosines serve", "phosphorylated tyrosines serve as", "tyrosines serve as binding", "serve as binding sites", "as binding sites for", "binding sites for the", "sites for the recruitment", "for the recruitment of", "the recruitment of signal", "recruitment of signal transducers", "of signal transducers and", "signal transducers and activators", "transducers and activators of", "and activators of intracellular", "activators of intracellular substrates", "intracellular substrates which", "substrates which then", "which then stimulate intracellular", "then stimulate intracellular signal", "stimulate intracellular signal transduction", "intracellular signal transduction cascades", "signal transduction cascades that", "transduction cascades that are", "cascades that are involved", "that are involved in", "are involved in regulating", "involved in regulating cellular", "in regulating cellular proliferation", "cellular proliferation differentiation", "differentiation and survival.", "and survival. recruitment of", "survival. recruitment of complexes", "recruitment of complexes containing", "of complexes containing grb2", "complexes containing grb2 and", "containing grb2 and sos1", "grb2 and sos1 to", "and sos1 to phosphorylated", "sos1 to phosphorylated egfr", "to phosphorylated egfr dimers", "phosphorylated egfr dimers either", "egfr dimers either directly", "either directly through", "directly through phosphotyrosine", "through phosphotyrosine residues that", "phosphotyrosine residues that serve", "residues that serve as", "that serve as grb2", "serve as grb2 docking", "as grb2 docking sites", "docking sites or", "sites or indirectly", "or indirectly through", "indirectly through shc1", "shc1 recruitment promotes", "recruitment promotes gdp", "promotes gdp to gtp", "gdp to gtp exchange", "to gtp exchange on", "gtp exchange on ras", "on ras resulting", "ras resulting in", "resulting in the activation", "in the activation of", "the activation of raf/map", "activation of raf/map kinase", "of raf/map kinase cascade.", "raf/map kinase cascade. binding", "kinase cascade. binding of", "cascade. binding of complexes", "binding of complexes of", "of complexes of grb2", "complexes of grb2 and", "of grb2 and gab1", "grb2 and gab1 to", "and gab1 to phosphorylated", "gab1 to phosphorylated egfr", "phosphorylated egfr dimers leads", "egfr dimers leads to", "dimers leads to formation", "leads to formation of", "to formation of the", "formation of the active", "of the active pi3k", "the active pi3k complex", "pi3k complex conversion", "complex conversion of", "conversion of pip2 into", "of pip2 into pip3", "into pip3 and", "pip3 and activation", "and activation of akt", "activation of akt signaling.", "of akt signaling. phospholipase", "akt signaling. phospholipase c", "signaling. phospholipase c gamma1", "c gamma1 plcg1", "plcg1 can also", "can also be recruited", "also be recruited directly", "recruited directly through", "directly through egfr", "through egfr phosphotyrosine residues", "egfr phosphotyrosine residues that", "that serve as plcg1", "serve as plcg1 docking", "as plcg1 docking sites", "docking sites which", "sites which leads", "which leads to plcg1", "leads to plcg1 phosphorylation", "to plcg1 phosphorylation by", "plcg1 phosphorylation by egfr", "phosphorylation by egfr and", "by egfr and activation", "egfr and activation of", "and activation of dag", "activation of dag and", "of dag and ip3", "dag and ip3 signaling.", "and ip3 signaling. egfr", "ip3 signaling. egfr signaling", "signaling. egfr signaling is", "egfr signaling is downregulated", "signaling is downregulated by", "is downregulated by the", "downregulated by the action", "by the action of", "the action of ubiquitin", "action of ubiquitin ligase", "of ubiquitin ligase cbl.", "ubiquitin ligase cbl. cbl", "ligase cbl. cbl binds", "cbl. cbl binds directly", "cbl binds directly to", "binds directly to the", "directly to the phosphorylated", "to the phosphorylated egfr", "the phosphorylated egfr dimer", "phosphorylated egfr dimer through", "egfr dimer through the", "dimer through the phosphotyrosine", "through the phosphotyrosine y1069", "phosphotyrosine y1069 i.e.", "y1069 i.e. y1045", "i.e. y1045 in the", "y1045 in the mature", "in the mature protein", "mature protein in", "protein in the", "in the c tail", "the c tail of", "c tail of egfr", "of egfr and", "egfr and after", "and after cbl is", "after cbl is phosphorylated", "cbl is phosphorylated by", "is phosphorylated by egfr", "by egfr it", "egfr it becomes", "it becomes active and", "becomes active and ubiquitinates", "active and ubiquitinates phosphorylated", "and ubiquitinates phosphorylated egfr", "ubiquitinates phosphorylated egfr dimers", "egfr dimers targeting", "dimers targeting them", "targeting them for degradation.", "them for degradation. positive", "for degradation. positive regulation", "degradation. positive regulation of", "positive regulation of egfr", "regulation of egfr signaling", "of egfr signaling by", "egfr signaling by direct", "signaling by direct association", "by direct association of", "direct association of egfr", "association of egfr with", "of egfr with accessory", "egfr with accessory proteins", "with accessory proteins such", "accessory proteins such as", "proteins such as aamp", "such as aamp and", "as aamp and fam83b", "aamp and fam83b is", "and fam83b is being", "fam83b is being investigated.", "is being investigated. for", "being investigated. for review", "investigated. for review of", "for review of egfr", "review of egfr signaling", "egfr signaling please", "signaling please refer", "please refer to carpenter", "refer to carpenter 1999", "carpenter 1999 wells", "1999 wells 1999", "wells 1999 schlessinger", "1999 schlessinger 2002", "schlessinger 2002 herbst", "2002 herbst 2004", "herbst 2004 avraham", "2004 avraham and", "and yarden 2011", "2011 bartel et", "bartel et al. 2016", "al. 2016 uribe", "2016 uribe et", "uribe et al. 2021", "al. 2021 keflee", "2021 keflee et", "keflee et al. 2022.", "the epidermal growth factor receptor", "growth factor receptor egfr", "receptor egfr is", "egfr is one member", "is one member of the", "one member of the erbb", "member of the erbb family", "of the erbb family of", "the erbb family of transmembrane", "erbb family of transmembrane glycoprotein", "family of transmembrane glycoprotein tyrosine", "of transmembrane glycoprotein tyrosine receptor", "transmembrane glycoprotein tyrosine receptor kinases", "tyrosine receptor kinases rtk", "receptor kinases rtk .", "kinases rtk . binding", "rtk . binding of egfr", ". binding of egfr to", "binding of egfr to its", "of egfr to its ligands", "egfr to its ligands induces", "to its ligands induces conformational", "its ligands induces conformational change", "ligands induces conformational change that", "induces conformational change that unmasks", "conformational change that unmasks the", "change that unmasks the dimerization", "that unmasks the dimerization interface", "unmasks the dimerization interface in", "the dimerization interface in the", "dimerization interface in the extracellular", "interface in the extracellular domain", "in the extracellular domain of", "the extracellular domain of egfr", "domain of egfr leading", "of egfr leading to", "egfr leading to receptor", "to receptor homo or", "receptor homo or heterodimerization", "homo or heterodimerization at", "or heterodimerization at the cell", "heterodimerization at the cell surface.", "at the cell surface. dimerization", "the cell surface. dimerization of", "cell surface. dimerization of the", "surface. dimerization of the extracellular", "dimerization of the extracellular regions", "of the extracellular regions of", "the extracellular regions of egfr", "extracellular regions of egfr triggers", "regions of egfr triggers additional", "of egfr triggers additional conformational", "egfr triggers additional conformational change", "triggers additional conformational change of", "additional conformational change of the", "conformational change of the cytoplasmic", "change of the cytoplasmic egfr", "of the cytoplasmic egfr regions", "cytoplasmic egfr regions enabling", "egfr regions enabling the", "regions enabling the kinase", "enabling the kinase domains of", "the kinase domains of two", "kinase domains of two egfr", "domains of two egfr molecules", "of two egfr molecules to", "two egfr molecules to achieve", "egfr molecules to achieve the", "molecules to achieve the catalytically", "to achieve the catalytically active", "achieve the catalytically active conformation.", "the catalytically active conformation. ligand", "catalytically active conformation. ligand activated", "active conformation. ligand activated egfr", "conformation. ligand activated egfr dimers", "ligand activated egfr dimers trans", "activated egfr dimers trans autophosphorylate", "egfr dimers trans autophosphorylate on", "dimers trans autophosphorylate on tyrosine", "trans autophosphorylate on tyrosine residues", "autophosphorylate on tyrosine residues in", "on tyrosine residues in the", "tyrosine residues in the cytoplasmic", "residues in the cytoplasmic tail", "in the cytoplasmic tail of", "the cytoplasmic tail of the", "cytoplasmic tail of the receptor.", "tail of the receptor. phosphorylated", "of the receptor. phosphorylated tyrosines", "the receptor. phosphorylated tyrosines serve", "receptor. phosphorylated tyrosines serve as", "phosphorylated tyrosines serve as binding", "tyrosines serve as binding sites", "serve as binding sites for", "as binding sites for the", "binding sites for the recruitment", "sites for the recruitment of", "for the recruitment of signal", "the recruitment of signal transducers", "recruitment of signal transducers and", "of signal transducers and activators", "signal transducers and activators of", "transducers and activators of intracellular", "and activators of intracellular substrates", "of intracellular substrates which", "intracellular substrates which then", "substrates which then stimulate", "which then stimulate intracellular signal", "then stimulate intracellular signal transduction", "stimulate intracellular signal transduction cascades", "intracellular signal transduction cascades that", "signal transduction cascades that are", "transduction cascades that are involved", "cascades that are involved in", "that are involved in regulating", "are involved in regulating cellular", "involved in regulating cellular proliferation", "regulating cellular proliferation differentiation", "proliferation differentiation and", "differentiation and survival. recruitment", "and survival. recruitment of complexes", "survival. recruitment of complexes containing", "recruitment of complexes containing grb2", "of complexes containing grb2 and", "complexes containing grb2 and sos1", "containing grb2 and sos1 to", "grb2 and sos1 to phosphorylated", "and sos1 to phosphorylated egfr", "sos1 to phosphorylated egfr dimers", "to phosphorylated egfr dimers either", "phosphorylated egfr dimers either directly", "dimers either directly through", "either directly through phosphotyrosine", "directly through phosphotyrosine residues", "through phosphotyrosine residues that serve", "phosphotyrosine residues that serve as", "residues that serve as grb2", "that serve as grb2 docking", "serve as grb2 docking sites", "grb2 docking sites or", "docking sites or indirectly", "or indirectly through shc1", "indirectly through shc1 recruitment", "through shc1 recruitment promotes", "shc1 recruitment promotes gdp", "recruitment promotes gdp to", "promotes gdp to gtp exchange", "gdp to gtp exchange on", "to gtp exchange on ras", "exchange on ras resulting", "on ras resulting in", "ras resulting in the", "resulting in the activation of", "in the activation of raf/map", "the activation of raf/map kinase", "activation of raf/map kinase cascade.", "of raf/map kinase cascade. binding", "raf/map kinase cascade. binding of", "kinase cascade. binding of complexes", "cascade. binding of complexes of", "binding of complexes of grb2", "of complexes of grb2 and", "complexes of grb2 and gab1", "of grb2 and gab1 to", "grb2 and gab1 to phosphorylated", "and gab1 to phosphorylated egfr", "gab1 to phosphorylated egfr dimers", "to phosphorylated egfr dimers leads", "phosphorylated egfr dimers leads to", "egfr dimers leads to formation", "dimers leads to formation of", "leads to formation of the", "to formation of the active", "formation of the active pi3k", "of the active pi3k complex", "active pi3k complex conversion", "pi3k complex conversion of", "complex conversion of pip2", "conversion of pip2 into pip3", "pip2 into pip3 and", "into pip3 and activation", "pip3 and activation of", "and activation of akt signaling.", "activation of akt signaling. phospholipase", "of akt signaling. phospholipase c", "akt signaling. phospholipase c gamma1", "phospholipase c gamma1 plcg1", "gamma1 plcg1 can", "plcg1 can also be", "can also be recruited directly", "be recruited directly through", "recruited directly through egfr", "directly through egfr phosphotyrosine", "through egfr phosphotyrosine residues that", "egfr phosphotyrosine residues that serve", "residues that serve as plcg1", "that serve as plcg1 docking", "serve as plcg1 docking sites", "plcg1 docking sites which", "docking sites which leads", "sites which leads to", "which leads to plcg1 phosphorylation", "leads to plcg1 phosphorylation by", "to plcg1 phosphorylation by egfr", "plcg1 phosphorylation by egfr and", "phosphorylation by egfr and activation", "by egfr and activation of", "egfr and activation of dag", "and activation of dag and", "activation of dag and ip3", "of dag and ip3 signaling.", "dag and ip3 signaling. egfr", "and ip3 signaling. egfr signaling", "ip3 signaling. egfr signaling is", "signaling. egfr signaling is downregulated", "egfr signaling is downregulated by", "signaling is downregulated by the", "is downregulated by the action", "downregulated by the action of", "by the action of ubiquitin", "the action of ubiquitin ligase", "action of ubiquitin ligase cbl.", "of ubiquitin ligase cbl. cbl", "ubiquitin ligase cbl. cbl binds", "ligase cbl. cbl binds directly", "cbl. cbl binds directly to", "cbl binds directly to the", "binds directly to the phosphorylated", "directly to the phosphorylated egfr", "to the phosphorylated egfr dimer", "the phosphorylated egfr dimer through", "phosphorylated egfr dimer through the", "egfr dimer through the phosphotyrosine", "dimer through the phosphotyrosine y1069", "the phosphotyrosine y1069 i.e.", "phosphotyrosine y1069 i.e. y1045", "y1069 i.e. y1045 in", "i.e. y1045 in the mature", "y1045 in the mature protein", "the mature protein in", "mature protein in the", "protein in the c", "in the c tail of", "the c tail of egfr", "tail of egfr and", "of egfr and after", "egfr and after cbl", "and after cbl is phosphorylated", "after cbl is phosphorylated by", "cbl is phosphorylated by egfr", "phosphorylated by egfr it", "by egfr it becomes", "egfr it becomes active", "it becomes active and ubiquitinates", "becomes active and ubiquitinates phosphorylated", "active and ubiquitinates phosphorylated egfr", "and ubiquitinates phosphorylated egfr dimers", "phosphorylated egfr dimers targeting", "egfr dimers targeting them", "dimers targeting them for", "targeting them for degradation. positive", "them for degradation. positive regulation", "for degradation. positive regulation of", "degradation. positive regulation of egfr", "positive regulation of egfr signaling", "regulation of egfr signaling by", "of egfr signaling by direct", "egfr signaling by direct association", "signaling by direct association of", "by direct association of egfr", "direct association of egfr with", "association of egfr with accessory", "of egfr with accessory proteins", "egfr with accessory proteins such", "with accessory proteins such as", "accessory proteins such as aamp", "proteins such as aamp and", "such as aamp and fam83b", "as aamp and fam83b is", "aamp and fam83b is being", "and fam83b is being investigated.", "fam83b is being investigated. for", "is being investigated. for review", "being investigated. for review of", "investigated. for review of egfr", "for review of egfr signaling", "of egfr signaling please", "egfr signaling please refer", "signaling please refer to", "please refer to carpenter 1999", "to carpenter 1999 wells", "carpenter 1999 wells 1999", "wells 1999 schlessinger 2002", "schlessinger 2002 herbst 2004", "herbst 2004 avraham and", "2004 avraham and yarden", "avraham and yarden 2011", "yarden 2011 bartel", "2011 bartel et al.", "et al. 2016 uribe", "al. 2016 uribe et", "2016 uribe et al.", "et al. 2021 keflee", "al. 2021 keflee et", "2021 keflee et al." ] }, { "record_id": "GLY_000594_1_132", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "179409", "r hsa", "hsa 179409", "r hsa 179409" ] }, { "record_id": "GLY_000594_1_132", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "apc cdc20", "cdc20 mediated", "mediated degradation", "degradation of", "of nek2a", "apc cdc20 mediated", "cdc20 mediated degradation", "mediated degradation of", "degradation of nek2a", "apc cdc20 mediated degradation", "cdc20 mediated degradation of", "mediated degradation of nek2a", "apc cdc20 mediated degradation of", "cdc20 mediated degradation of nek2a", "like cyclin", "cyclin a", "nima related", "related kinase", "kinase 2a", "is degraded", "degraded during", "during pro", "pro metaphase", "metaphase in", "in a", "a checkpoint", "checkpoint independent", "independent manner.", "like cyclin a", "a nima", "nima related kinase", "related kinase 2a", "2a nek2a", "is degraded during", "degraded during pro", "during pro metaphase", "pro metaphase in", "metaphase in a", "in a checkpoint", "a checkpoint independent", "checkpoint independent manner.", "cyclin a nima", "a nima related", "nima related kinase 2a", "kinase 2a nek2a", "nek2a is", "is degraded during pro", "degraded during pro metaphase", "during pro metaphase in", "pro metaphase in a", "metaphase in a checkpoint", "in a checkpoint independent", "a checkpoint independent manner.", "like cyclin a nima", "cyclin a nima related", "a nima related kinase", "related kinase 2a nek2a", "nek2a is degraded", "is degraded during pro metaphase", "degraded during pro metaphase in", "during pro metaphase in a", "pro metaphase in a checkpoint", "metaphase in a checkpoint independent", "in a checkpoint independent manner." ] }, { "record_id": "GLY_000594_1_133", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "179812", "r hsa", "hsa 179812", "r hsa 179812" ] }, { "record_id": "GLY_000594_1_133", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "grb2 events", "events in", "in egfr", "egfr signaling", "grb2 events in", "events in egfr", "in egfr signaling", "grb2 events in egfr", "events in egfr signaling", "grb2 events in egfr signaling", "autophosphorylated egfr", "egfr tyrosine", "tyrosine residues", "residues are", "are docking", "docking sites", "sites for", "for many", "many downstream", "downstream effectors", "effectors in", "egfr signaling.", "signaling. the", "the adaptor", "adaptor protein", "protein grb2", "grb2 binds", "binds to", "to phosphotyrosine", "phosphotyrosine residues", "residues in", "in the", "the c", "c tail", "tail of", "of egfr", "egfr through", "through its", "its sh2", "sh2 domain.", "domain. grb2", "grb2 is", "is constitutively", "constitutively associated", "associated with", "with sos", "a guanine", "guanine nucleotide", "nucleotide exchange", "exchange factor", "factor of", "of ras.", "ras. grb2", "grb2 binding", "binding to", "to phosphorylated", "phosphorylated egfr", "egfr results", "results in", "the recruitment", "recruitment of", "of sos", "sos to", "to the", "the plasma", "plasma membrane", "membrane where", "where it", "it comes", "comes in", "in proximity", "proximity to", "to ras.", "ras. this", "this mechanism", "mechanism has", "has been", "been 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"downstream effectors in egfr", "effectors in egfr signaling.", "in egfr signaling. the", "egfr signaling. the adaptor", "signaling. the adaptor protein", "the adaptor protein grb2", "adaptor protein grb2 binds", "protein grb2 binds to", "grb2 binds to phosphotyrosine", "binds to phosphotyrosine residues", "to phosphotyrosine residues in", "phosphotyrosine residues in the", "residues in the c", "in the c tail", "the c tail of", "c tail of egfr", "tail of egfr through", "of egfr through its", "egfr through its sh2", "through its sh2 domain.", "its sh2 domain. grb2", "sh2 domain. grb2 is", "domain. grb2 is constitutively", "grb2 is constitutively associated", "is constitutively associated with", "constitutively associated with sos", "with sos a", "sos a guanine", "a guanine nucleotide exchange", "guanine nucleotide exchange factor", "nucleotide exchange factor of", "exchange factor of ras.", "factor of ras. grb2", "of ras. grb2 binding", "ras. grb2 binding to", "grb2 binding to 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"sites for many downstream effectors", "for many downstream effectors in", "many downstream effectors in egfr", "downstream effectors in egfr signaling.", "effectors in egfr signaling. the", "in egfr signaling. the adaptor", "egfr signaling. the adaptor protein", "signaling. the adaptor protein grb2", "the adaptor protein grb2 binds", "adaptor protein grb2 binds to", "protein grb2 binds to phosphotyrosine", "grb2 binds to phosphotyrosine residues", "binds to phosphotyrosine residues in", "to phosphotyrosine residues in the", "phosphotyrosine residues in the c", "residues in the c tail", "in the c tail of", "the c tail of egfr", "c tail of egfr through", "tail of egfr through its", "of egfr through its sh2", "egfr through its sh2 domain.", "through its sh2 domain. grb2", "its sh2 domain. grb2 is", "sh2 domain. grb2 is constitutively", "domain. grb2 is constitutively associated", "grb2 is constitutively associated with", "is constitutively associated with sos", "associated with sos a", "with sos a guanine", "sos a guanine nucleotide", "a guanine nucleotide exchange factor", "guanine nucleotide exchange factor of", "nucleotide exchange factor of ras.", "exchange factor of ras. grb2", "factor of ras. grb2 binding", "of ras. grb2 binding to", "ras. grb2 binding to phosphorylated", "grb2 binding to phosphorylated egfr", "binding to phosphorylated egfr results", "to phosphorylated egfr results in", "phosphorylated egfr results in the", "egfr results in the recruitment", "results in the recruitment of", "in the recruitment of sos", "the recruitment of sos to", "recruitment of sos to the", "of sos to the plasma", "sos to the plasma membrane", "to the plasma membrane where", "the plasma membrane where it", "plasma membrane where it comes", "membrane where it comes in", "where it comes in proximity", "it comes in proximity to", "comes in proximity to ras.", "in proximity to ras. this", "proximity to ras. this mechanism", "to ras. this mechanism has", "ras. this mechanism has been", "this mechanism has been seen", "mechanism has been seen to", "has been seen to be", "been seen to be the", "seen to be the model", "to be the model for", "be the model for ras", "the model for ras activation." ] }, { "record_id": "GLY_000594_1_134", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "180292", "r hsa", "hsa 180292", "r hsa 180292" ] }, { "record_id": "GLY_000594_1_134", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gab1 signalosome", "gab1 is", "is recruited", "recruited to", "to the", "the activated", "activated egfr", "egfr indirectly", "through grb2.", "grb2. gab1", "gab1 acts", "acts as", "as an", "an adaptor", "adaptor protein", "protein that", "that enables", "enables formation", "formation of", "of an", "an active", "active pik3", "through recruitment", "recruitment of", "of pik3", "pik3 regulatory", "regulatory subunit", "subunit pik3r1", "also known", "known as", 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conversion to", "its conversion to pip3", "to pip3 which", "pip3 which leads", "which leads to the", "leads to the activation", "to the activation of", "the activation of the", "activation of the akt", "of the akt signaling.", "gab1 is recruited to the", "is recruited to the activated", "recruited to the activated egfr", "to the activated egfr indirectly", "activated egfr indirectly through", "egfr indirectly through grb2.", "indirectly through grb2. gab1", "through grb2. gab1 acts as", "grb2. gab1 acts as an", "gab1 acts as an adaptor", "acts as an adaptor protein", "as an adaptor protein that", "an adaptor protein that enables", "adaptor protein that enables formation", "protein that enables formation of", "that enables formation of an", "enables formation of an active", "formation of an active pik3", "an active pik3 through", "active pik3 through recruitment", "pik3 through recruitment of", "through recruitment of pik3 regulatory", "recruitment of pik3 regulatory subunit", "of pik3 regulatory subunit pik3r1", "regulatory subunit pik3r1 also", "subunit pik3r1 also known", "pik3r1 also known as", "as pi3kp85 which", "pi3kp85 which subsequently", "which subsequently recruits pik3 catalytic", "subsequently recruits pik3 catalytic subunit", "recruits pik3 catalytic subunit pik3ca", "catalytic subunit pik3ca also", "subunit pik3ca also known", "pik3ca also known as", "also known as pi3kp110 .", "known as pi3kp110 . pik3", "pi3kp110 . pik3 in", ". pik3 in complex", "pik3 in complex with", "complex with egfr grb2", "with egfr grb2 and", "egfr grb2 and gab1", "grb2 and gab1 catalyzes", "and gab1 catalyzes phosphorylation", "gab1 catalyzes phosphorylation of", "catalyzes phosphorylation of pip2 and", "phosphorylation of pip2 and its", "of pip2 and its conversion", "pip2 and its conversion to", "and its conversion to pip3", "conversion to pip3 which", "to pip3 which leads", "pip3 which leads to", "which leads to the activation", "leads to the activation of", "to the activation of the", "the activation of the akt", "activation of the akt signaling." ] }, { "record_id": "GLY_000594_1_135", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "180336", "r hsa", "hsa 180336", "r hsa 180336" ] }, { "record_id": "GLY_000594_1_135", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc1 events", "events in", "in egfr", "egfr signaling", "shc1 events in", "events in egfr", "in egfr signaling", "shc1 events in egfr", "events in egfr signaling", "shc1 events in egfr signaling", "grb2 can", "can bind", "bind egfr", "egfr directly", "directly or", "or through", "through another", "another sh2", "sh2 containing", "containing protein", "shc1. this", "this association", "association leads", "to ras", "ras activation.", "grb2 can bind", "can bind egfr", "bind egfr directly", "egfr directly or", "directly or through", "or through another", "through another sh2", "another sh2 containing", "sh2 containing protein", "protein shc1.", "shc1. this association", "this association leads", "leads to", "to ras activation.", "grb2 can bind egfr", "can bind egfr directly", "bind egfr directly or", "egfr directly or through", "directly or through another", "or through another sh2", "through another sh2 containing", "another sh2 containing protein", "containing protein shc1.", "protein shc1. this", "shc1. this association leads", "association leads to", "leads to ras", "grb2 can bind egfr directly", "can bind egfr directly or", "bind egfr directly or through", "egfr directly or through another", "directly or through another sh2", "or through another sh2 containing", "through another sh2 containing protein", "sh2 containing protein shc1.", "containing protein shc1. this", "protein shc1. this association", "this association leads to", "association leads to ras", "leads to ras activation." ] }, { "record_id": "GLY_000594_1_136", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "180534", "r hsa", "hsa 180534", "r hsa 180534" ] }, { "record_id": "GLY_000594_1_136", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "vpu mediated", "mediated degradation", "degradation of", "of cd4", "vpu mediated degradation", "mediated degradation of", "degradation of cd4", "vpu mediated degradation of", "mediated degradation of cd4", "vpu mediated degradation of cd4", "the hiv", "hiv 1", "1 vpu", "vpu protein", "protein promotes", "promotes the", "the degradation", "of the", "the cd4", "cd4 receptor", "receptor by", "recruiting an", "an scf", "scf like", "like ubiquitination", "ubiquitination complex", "complex that", "that promotes", "promotes cd4", "cd4 degradation.", "vpu links", "links beta", "beta trcp", "trcp to", "to cd4", "cd4 at", "at the", "the er", "er membrane", "membrane through", "through interactions", "interactions with", "with beta", 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deamination", "al. 2003 .
deamination changes", "2003 .
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deamination", "et al. 2003 .
deamination changes", "al. 2003 .
deamination changes cytidine", "2003 .
deamination changes cytidine to", ".
deamination changes cytidine to uracil", "changes cytidine to uracil and", "cytidine to uracil and thus", "to uracil and thus results", "uracil and thus results in", "and thus results in g", "thus results in g to", "results in g to a", "in g to a transitions", "g to a transitions and", "to a transitions and stop", "a transitions and stop codons", "transitions and stop codons in", "and stop codons in the", "stop codons in the provirus.", "codons in the provirus. the", "in the provirus. the aberrant", "the provirus. the aberrant cdnas", "provirus. the aberrant cdnas produced", "the aberrant cdnas produced in", "aberrant cdnas produced in the", "cdnas produced in the infected", "produced in the infected cell", "in the infected cell can", "the infected cell can either", "infected cell can either be", "cell can either be integrated", "can either be integrated in", "either be integrated in form", "be integrated in form of", "integrated in form of non", "in form of non functional", "form of non functional proviruses", "of non functional proviruses or", "non functional proviruses or degraded.", "proviruses or degraded. vif", "degraded. vif counteracts", "vif counteracts the antiviral", "counteracts the antiviral activity of", "the antiviral activity of apobec3g", "antiviral activity of apobec3g by", "activity of apobec3g by associating", "of apobec3g by associating directly", "apobec3g by associating directly with", "by associating directly with it", "associating directly with it and", "directly with it and promoting", "with it and promoting its", "it and promoting its polyubiquitination", "and promoting its polyubiquitination and", "promoting its polyubiquitination and degradation", "its polyubiquitination and degradation by", "polyubiquitination and degradation by the", "and degradation by the 26s", "degradation by the 26s proteasome.", "by the 26s proteasome.
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is", "is implicated", "implicated in", "in the", "the control", "control of", "of almost", "almost all", "all cellular", "cellular functions.", "functions. one", "one of", "of the", "the best", "best understood", "understood rtks", "rtks is", "is epidermal", "epidermal growth", "growth factor", "factor receptor", "egfr .", ". growth", "growth factors", "factors can", "can bind", "bind to", "to egfr", "egfr and", "and activate", "activate it", "it to", "to initiate", "initiate signalling", "signalling cascades", "cascades within", "within the", "the cell.", "cell. egfrs", "egfrs can", "can also", "also be", "be recruited", "recruited to", "to clathrin", "clathrin coated", "coated pits", "pits which", "which can", "can be", "be internalised", "internalised into", "into endocytic", "endocytic vesicles.", "vesicles. from", "from here", "can either", "either be", "be recycled", "recycled back", "back to", "to the", "the plasma", "plasma membrane", "membrane or", "or directed", "directed 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the", "tumorigenesis.

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the", "in tumorigenesis.

the proto", "tumorigenesis.

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cbl", "negatively regulated.

cbl also", "regulated.

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the", "seen in tumorigenesis.

the proto", "in tumorigenesis.

the proto oncogene", "tumorigenesis.

the proto oncogene cbl", "proto oncogene cbl can", "oncogene cbl can negatively", "cbl can negatively regulate", "can negatively regulate egfr", "negatively regulate egfr signalling.", "regulate egfr signalling. the", "egfr signalling. the cbl", "signalling. the cbl family", "the cbl family of", "cbl family of ring", "family of ring type", "of ring type ubiquitin", "ring type ubiquitin ligases", "type ubiquitin ligases are", "ubiquitin ligases are able", "ligases are able to", "are able to poly", "able to poly ubiquitinate", "to poly ubiquitinate egfr", "ubiquitinate egfr an", "egfr an essential", "an essential step in", "essential step in egfr", "step in egfr degradation.", "in egfr degradation. all", "egfr degradation. all cbl", "degradation. all cbl proteins", "all cbl proteins have", "cbl proteins have a", "proteins have a unique", "have a unique domain", "a unique domain that", "unique domain that recognises", "domain that recognises phosphorylated", "that recognises phosphorylated tyrosine", "recognises phosphorylated tyrosine residues", "phosphorylated tyrosine residues on", "tyrosine residues on activated", "residues on activated egfrs.", "on activated egfrs. they", "activated egfrs. they also", "egfrs. they also direct", "they also direct the", "also direct the ubiquitination", "direct the ubiquitination and", "the ubiquitination and degradation", "ubiquitination and degradation of", "and degradation of activated", "degradation of activated egfrs", "of activated egfrs by", "activated egfrs by recruiting", "egfrs by recruiting ubiquitin", "by recruiting ubiquitin conjugation", "recruiting ubiquitin conjugation enzymes.", "ubiquitin conjugation enzymes. cbl", "conjugation enzymes. cbl proteins", "enzymes. cbl proteins function", "cbl proteins function by", "proteins function by specifically", "function by specifically targeting", "by specifically targeting activated", "specifically targeting activated egfrs", "targeting activated egfrs and", "activated egfrs and mediating", "egfrs and mediating their", "and mediating their down", "mediating their down regulation", "down regulation thus", "regulation thus providing", "thus providing a means", "providing a means by", "a means by which", "means by which signaling", "by which signaling processes", "which signaling processes can", "signaling processes can be", "processes can be negatively", "can be negatively regulated.

cbl", "be negatively regulated.

cbl also", "negatively regulated.

cbl also promotes", "regulated.

cbl also promotes receptor", "also promotes receptor internalization", "promotes receptor internalization via", "receptor internalization via it's", "internalization via it's interaction", "via it's interaction with", "it's interaction with an", "interaction with an adaptor", "with an adaptor protein", "adaptor protein cin85", "cin85 cbl interacting", "cbl interacting protein of", "interacting protein of 85kda", "protein of 85kda .", "of 85kda . cin85", "85kda . cin85 binds", ". cin85 binds to", "cin85 binds to cbl", "binds to cbl via", "to cbl via it's", "cbl via it's sh3", "via it's sh3 domain", "it's sh3 domain and", "sh3 domain and is", "domain and is enhanced", "and is enhanced by", "is enhanced by the", "enhanced by the egfr", "by the egfr induced", "the egfr induced tyrosine", "egfr induced tyrosine phosphorylation", "induced tyrosine phosphorylation of", "tyrosine phosphorylation of cbl.", "phosphorylation of cbl. the", "of cbl. the proline", "cbl. the proline rich", "the proline rich region", "proline rich region of", "rich region of cin85", "region of cin85 interacts", "of cin85 interacts with", "cin85 interacts with endophilins", "interacts with endophilins which", "with endophilins which are", "endophilins which are regulatory", "which are regulatory components", "are regulatory components of", "regulatory components of clathrin", "components of clathrin coated", "of clathrin coated vesicles", "coated vesicles ccvs", "vesicles ccvs .", "ccvs . endophilins bind", ". endophilins bind to", "endophilins bind to membranes", "bind to membranes and", "to membranes and induce", "membranes and induce membrane", "and induce membrane curvature", "membrane curvature in", "curvature in conjunction", "in conjunction with other", "conjunction with other proteins", "with other proteins involved", "other proteins involved in", "proteins involved in ccv", "involved in ccv formation.", "in ccv formation. the", "ccv formation. the rapid", "formation. the rapid recruitment", "the rapid recruitment of", "rapid recruitment of endophilin", "recruitment of endophilin to", "of endophilin to the", "endophilin to the activated", "to the activated receptor", "the activated receptor complex", "activated receptor complex by", "receptor complex by cin85", "complex by cin85 is", "by cin85 is the", "cin85 is the mechanism", "is the mechanism which", "the mechanism which controls", "mechanism which controls receptor", "which controls receptor internalization.", "regulation of receptor tyrosine kinase", "receptor tyrosine kinase rtk", "kinase rtk activity", "rtk activity is implicated", "activity is implicated in the", "is implicated in the control", "implicated in the control of", "in the control of almost", "the control of almost all", "control of almost all cellular", "of almost all cellular functions.", "almost all cellular functions. one", "all cellular functions. one of", "cellular functions. one of the", "functions. one of the best", "one of the best understood", "of the best understood rtks", "the best understood rtks is", "best understood rtks is epidermal", "understood rtks is epidermal growth", "rtks is epidermal growth factor", "is epidermal growth factor receptor", "growth factor receptor egfr", "factor receptor egfr .", "receptor egfr . growth", "egfr . growth factors can", ". growth factors can bind", "growth factors can bind to", "factors can bind to egfr", "can bind to egfr and", "bind to egfr and activate", "to egfr and activate it", "egfr and activate it to", "and activate it to initiate", "activate it to initiate signalling", "it to initiate signalling cascades", "to initiate signalling cascades within", "initiate signalling cascades within the", "signalling cascades within the cell.", "cascades within the cell. egfrs", "within the cell. egfrs can", "the cell. egfrs can also", "cell. egfrs can also be", "egfrs can also be recruited", "can also be recruited to", "also be recruited to clathrin", "be recruited to clathrin coated", "recruited to clathrin coated pits", "to clathrin coated pits which", "clathrin coated pits which can", "coated pits which can be", "pits which can be internalised", "which can be internalised into", "can be internalised into endocytic", "be internalised into endocytic vesicles.", "internalised into endocytic vesicles. from", "into endocytic vesicles. from here", "vesicles. from here egfrs", "from here egfrs can", "here egfrs can either", "egfrs can either be recycled", "can either be recycled back", "either be recycled back to", "be recycled back to the", "recycled back to the plasma", "back to the plasma membrane", "to the plasma membrane or", "the plasma membrane or directed", "plasma membrane or directed to", "membrane or directed to lysosomes", "or directed to lysosomes for", "directed to lysosomes for destruction.this", "to lysosomes for destruction.this provides", "lysosomes for destruction.this provides a", "for destruction.this provides a mechanism", "destruction.this provides a mechanism by", "provides a mechanism by which", "a mechanism by which egfr", "mechanism by which egfr signalling", "by which egfr signalling is", "which egfr signalling is negatively", "egfr signalling is negatively regulated", "signalling is negatively regulated and", "is negatively regulated and controls", "negatively regulated and controls the", "regulated and controls the strength", "and controls the strength and", "controls the strength and duration", "the strength and duration of", "strength and duration of egfr", "and duration of egfr induced", "duration of egfr induced signals.", "of egfr induced signals. it", "egfr induced signals. it also", "induced signals. it also prevents", "signals. it also prevents egfr", "it also prevents egfr hyperactivation", "also prevents egfr hyperactivation as", "prevents egfr hyperactivation as commonly", "egfr hyperactivation as commonly seen", "hyperactivation as commonly seen in", "as commonly seen in tumorigenesis.

the", "commonly seen in tumorigenesis.

the proto", "seen in tumorigenesis.

the proto oncogene", "in tumorigenesis.

the proto oncogene cbl", "tumorigenesis.

the proto oncogene cbl can", "proto oncogene cbl can negatively", "oncogene cbl can negatively regulate", "cbl can negatively regulate egfr", "can negatively regulate egfr signalling.", "negatively regulate egfr signalling. the", "regulate egfr signalling. the cbl", "egfr signalling. the cbl family", "signalling. the cbl family of", "the cbl family of ring", "cbl family of ring type", "family of ring type ubiquitin", "of ring type ubiquitin ligases", "ring type ubiquitin ligases are", "type ubiquitin ligases are able", "ubiquitin ligases are able to", "ligases are able to poly", "are able to poly ubiquitinate", "able to poly ubiquitinate egfr", "poly ubiquitinate egfr an", "ubiquitinate egfr an essential", "egfr an essential step", "an essential step in egfr", "essential step in egfr degradation.", "step in egfr degradation. all", "in egfr degradation. all cbl", "egfr degradation. all cbl proteins", "degradation. all cbl proteins have", "all cbl proteins have a", "cbl proteins have a unique", "proteins have a unique domain", "have a unique domain that", "a unique domain that recognises", "unique domain that recognises phosphorylated", "domain that recognises phosphorylated tyrosine", "that recognises phosphorylated tyrosine residues", "recognises phosphorylated tyrosine residues on", "phosphorylated tyrosine residues on activated", "tyrosine residues on activated egfrs.", "residues on activated egfrs. they", "on activated egfrs. they also", "activated egfrs. they also direct", "egfrs. they also direct the", "they also direct the ubiquitination", "also direct the ubiquitination and", "direct the ubiquitination and degradation", "the ubiquitination and degradation of", "ubiquitination and degradation of activated", "and degradation of activated egfrs", "degradation of activated egfrs by", "of activated egfrs by recruiting", "activated egfrs by recruiting ubiquitin", "egfrs by recruiting ubiquitin conjugation", "by recruiting ubiquitin conjugation enzymes.", "recruiting ubiquitin conjugation enzymes. cbl", "ubiquitin conjugation enzymes. cbl proteins", "conjugation enzymes. cbl proteins function", "enzymes. cbl proteins function by", "cbl proteins function by specifically", "proteins function by specifically targeting", "function by specifically targeting activated", "by specifically targeting activated egfrs", "specifically targeting activated egfrs and", "targeting activated egfrs and mediating", "activated egfrs and mediating their", "egfrs and mediating their down", "and mediating their down regulation", "their down regulation thus", "down regulation thus providing", "regulation thus providing a", "thus providing a means by", "providing a means by which", "a means by which signaling", "means by which signaling processes", "by which signaling processes can", "which signaling processes can be", "signaling processes can be negatively", "processes can be negatively regulated.

cbl", "can be negatively regulated.

cbl also", "be negatively regulated.

cbl also promotes", "negatively regulated.

cbl also promotes receptor", "regulated.

cbl also promotes receptor internalization", "also promotes receptor internalization via", "promotes receptor internalization via it's", "receptor internalization via it's interaction", "internalization via it's interaction with", "via it's interaction with an", "it's interaction with an adaptor", "interaction with an adaptor protein", "an adaptor protein cin85", "protein cin85 cbl", "cin85 cbl interacting protein", "cbl interacting protein of 85kda", "interacting protein of 85kda .", "protein of 85kda . cin85", "of 85kda . cin85 binds", "85kda . cin85 binds to", ". cin85 binds to cbl", "cin85 binds to cbl via", "binds to cbl via it's", "to cbl via it's sh3", "cbl via it's sh3 domain", "via it's sh3 domain and", "it's sh3 domain and is", "sh3 domain and is enhanced", "domain and is enhanced by", "and is enhanced by the", "is enhanced by the egfr", "enhanced by the egfr induced", "by the egfr induced tyrosine", "the egfr induced tyrosine phosphorylation", "egfr induced tyrosine phosphorylation of", "induced tyrosine phosphorylation of cbl.", "tyrosine phosphorylation of cbl. the", "phosphorylation of cbl. the proline", "of cbl. the proline rich", "cbl. the proline rich region", "the proline rich region of", "proline rich region of cin85", "rich region of cin85 interacts", "region of cin85 interacts with", "of cin85 interacts with endophilins", "cin85 interacts with endophilins which", "interacts with endophilins which are", "with endophilins which are regulatory", "endophilins which are regulatory components", "which are regulatory components of", "are regulatory components of clathrin", "regulatory components of clathrin coated", "components of clathrin coated vesicles", "clathrin coated vesicles ccvs", "coated vesicles ccvs .", "vesicles ccvs . endophilins", "ccvs . endophilins bind to", ". endophilins bind to membranes", "endophilins bind to membranes and", "bind to membranes and induce", "to membranes and induce membrane", "membranes and induce membrane curvature", "induce membrane curvature in", "membrane curvature in conjunction", "curvature in conjunction with", "in conjunction with other proteins", "conjunction with other proteins involved", "with other proteins involved in", "other proteins involved in ccv", "proteins involved in ccv formation.", "involved in ccv formation. the", "in ccv formation. the rapid", "ccv formation. the rapid recruitment", "formation. the rapid recruitment of", "the rapid recruitment of endophilin", "rapid recruitment of endophilin to", "recruitment of endophilin to the", "of endophilin to the activated", "endophilin to the activated receptor", "to the activated receptor complex", "the activated receptor complex by", "activated receptor complex by cin85", "receptor complex by cin85 is", "complex by cin85 is the", "by cin85 is the mechanism", "cin85 is the mechanism which", "is the mechanism which controls", "the mechanism which controls receptor", "mechanism which controls receptor internalization." ] }, { "record_id": "GLY_000594_1_144", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1834949", "r hsa", "hsa 1834949", "r hsa 1834949" ] }, { "record_id": "GLY_000594_1_144", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cytosolic sensors", "sensors of", "of pathogen", "pathogen associated", "associated dna", "cytosolic sensors of", "sensors of pathogen", "of pathogen associated", "pathogen associated dna", "cytosolic sensors of pathogen", "sensors of pathogen associated", "of pathogen associated dna", "cytosolic sensors of pathogen associated", "sensors of pathogen associated dna", "presence of", "dna in", "in cytosol", "cytosol induces", "induces type", "type i", "i ifn", "ifn production.", "production. several", "several intracellular", "intracellular receptors", "receptors have", "have been", "been implicated", "implicated to", "to some", "some degree.", "degree. these", "these include", "include dna", "dna dependent", "dependent activator", "activator of", "of interferon", "regulatory factors", "also called", "called z", "z dna", "dna binding", "binding protein", "protein 1", "absent in", "in melanoma", "melanoma 2", "rna polymerase", "polymerase iii", "pol iii", "ifn inducible", "inducible protein", "protein ifi16", "leucine rich", "rich repeat", "repeat flightless", "flightless interacting", "interacting protein", "deah box", "box helicases", "dhx9 and", "and dhx36", "dead box", "box helicase", "helicase ddx41", "meiotic recombination", "recombination 11", "11 homolog", "homolog a", "dependent protein", "protein kinase", "dna pk", "cyclic gmp", "gmp amp", "amp synthase", "and stimulator", "stimulator of", "interferon genes", "sting .

detection", ".

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detection of", ".

detection of cytosolic", "of cytosolic dna", "cytosolic dna requires", "dna requires multiple", "requires multiple and", "multiple and possibly", "and possibly redundant", "possibly redundant sensors", "redundant sensors leading", "sensors leading to", "leading to activation", "to activation of", "activation of the", "of the transcription", "the transcription factor", "transcription factor nf", "factor nf kappab", "nf kappab and", "kappab and tbk1", "and tbk1 mediated", "tbk1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of the", "transcription factor irf3.", "factor irf3. cytosolic", "irf3. cytosolic dna", "cytosolic dna also", "dna also activates", "also activates caspase", "activates caspase 1", "caspase 1 dependent", "1 dependent maturation", "dependent maturation of", "maturation of the", "of the pro", "the pro inflammatory", "pro inflammatory cytokines", "inflammatory cytokines interleukin", "cytokines interleukin il", "interleukin il 1beta", "il 1beta and", "1beta and il", "and il 18.", "il 18. this", "18. this pathway", "this pathway is", "pathway is mediated", "is mediated by", "mediated by aim2.", "presence of pathogen associated", "pathogen associated dna in", "associated dna in cytosol", "dna in cytosol induces", "in cytosol induces type", "cytosol induces type i", "induces type i ifn", "type i ifn production.", "i ifn production. several", "ifn production. several intracellular", "production. several intracellular receptors", "several intracellular receptors have", "intracellular receptors have been", "receptors have been implicated", "have been implicated to", "been implicated to some", "implicated to some degree.", "to some degree. these", "some degree. these include", "degree. these include dna", "these include dna dependent", "include dna dependent activator", "dna dependent activator of", "dependent activator of interferon", "of interferon ifn", "ifn regulatory factors", "regulatory factors dai", "dai also", "also called z dna", "called z dna binding", "z dna binding protein", "dna binding protein 1", "protein 1 zbp1", "zbp1 absent", "absent in melanoma 2", "melanoma 2 aim2", "aim2 rna", "polymerase iii pol", "iii pol iii", "iii ifn", "ifn inducible protein ifi16", "protein ifi16 leucine", "ifi16 leucine rich", "leucine rich repeat flightless", "rich repeat flightless interacting", "repeat flightless interacting protein", "flightless interacting protein 1", "protein 1 lrrfip1", "lrrfip1 deah", "box helicases dhx9", "helicases dhx9 and", "dhx36 dead", "dead box helicase ddx41", "helicase ddx41 meiotic", "ddx41 meiotic recombination", "meiotic recombination 11 homolog", "recombination 11 homolog a", "homolog a mre11", "mre11 dna", "dna dependent protein kinase", "protein kinase dna", "kinase dna pk", "pk cyclic", "cyclic gmp amp synthase", "amp synthase cgas", "cgas and stimulator", "and stimulator of interferon", "stimulator of interferon genes", "interferon genes sting", "genes sting .

detection", "sting .

detection of cytosolic", ".

detection of cytosolic dna", "of cytosolic dna requires", "cytosolic dna requires multiple", "dna requires multiple and", "requires multiple and possibly", "multiple and possibly redundant", "and possibly redundant sensors", "possibly redundant sensors leading", "redundant sensors leading to", "sensors leading to activation", "leading to activation of", "to activation of the", "activation of the transcription", "of the transcription factor", "the transcription factor nf", "transcription factor nf kappab", "factor nf kappab and", "nf kappab and tbk1", "kappab and tbk1 mediated", "and tbk1 mediated phosphorylation", "tbk1 mediated phosphorylation of", "mediated phosphorylation of the", "phosphorylation of the transcription", "the transcription factor irf3.", "transcription factor irf3. cytosolic", "factor irf3. cytosolic dna", "irf3. cytosolic dna also", "cytosolic dna also activates", "dna also activates caspase", "also activates caspase 1", "activates caspase 1 dependent", "caspase 1 dependent maturation", "1 dependent maturation of", "dependent maturation of the", "maturation of the pro", "of the pro inflammatory", "the pro inflammatory cytokines", "pro inflammatory cytokines interleukin", "inflammatory cytokines interleukin il", "cytokines interleukin il 1beta", "interleukin il 1beta and", "il 1beta and il", "1beta and il 18.", "and il 18. this", "il 18. this pathway", "18. this pathway is", "this pathway is mediated", "pathway is mediated by", "is mediated by aim2.", "presence of pathogen associated dna", "of pathogen associated dna in", "pathogen associated dna in cytosol", "associated dna in cytosol induces", "dna in cytosol induces type", "in cytosol induces type i", "cytosol induces type i ifn", "induces type i ifn production.", "type i ifn production. several", "i ifn production. several intracellular", "ifn production. several intracellular receptors", "production. several intracellular receptors have", "several intracellular receptors have been", "intracellular receptors have been implicated", "receptors have been implicated to", "have been implicated to some", "been implicated to some degree.", "implicated to some degree. these", "to some degree. these include", "some degree. these include dna", "degree. these include dna dependent", "these include dna dependent activator", "include dna dependent activator of", "dna dependent activator of interferon", "activator of interferon ifn", "interferon ifn regulatory", "dai also called", "also called z dna binding", "called z dna binding protein", "z dna binding protein 1", "binding protein 1 zbp1", "zbp1 absent in", "in melanoma 2 aim2", "aim2 rna polymerase", "rna polymerase iii pol", "polymerase iii pol iii", "pol iii ifn", "iii ifn inducible", "inducible protein ifi16 leucine", "protein ifi16 leucine rich", "ifi16 leucine rich repeat", "leucine rich repeat flightless interacting", "rich repeat flightless interacting protein", "repeat flightless interacting protein 1", "interacting protein 1 lrrfip1", "lrrfip1 deah box", "deah box helicases dhx9", "box helicases dhx9 and", "helicases dhx9 and dhx36", "and dhx36 dead", "dhx36 dead box", "box helicase ddx41 meiotic", "helicase ddx41 meiotic recombination", "ddx41 meiotic recombination 11", "meiotic recombination 11 homolog a", "11 homolog a mre11", "mre11 dna dependent", "dependent protein kinase dna", "protein kinase dna pk", "dna pk cyclic", "pk cyclic gmp", "gmp amp synthase cgas", "synthase cgas and", "cgas and stimulator of", "and stimulator of interferon genes", "of interferon genes sting", "interferon genes sting .

detection", "genes sting .

detection of", "sting .

detection of cytosolic dna", ".

detection of cytosolic dna requires", "of cytosolic dna requires multiple", "cytosolic dna requires multiple and", "dna requires multiple and possibly", "requires multiple and possibly redundant", "multiple and possibly redundant sensors", "and possibly redundant sensors leading", "possibly redundant sensors leading to", "redundant sensors leading to activation", "sensors leading to activation of", "leading to activation of the", "to activation of the transcription", "activation of the transcription factor", "of the transcription factor nf", "the transcription factor nf kappab", "transcription factor nf kappab and", "factor nf kappab and tbk1", "nf kappab and tbk1 mediated", "kappab and tbk1 mediated phosphorylation", "and tbk1 mediated phosphorylation of", "tbk1 mediated phosphorylation of the", "mediated phosphorylation of the transcription", "phosphorylation of the transcription factor", "of the transcription factor irf3.", "the transcription factor irf3. cytosolic", "transcription factor irf3. cytosolic dna", "factor irf3. cytosolic dna also", "irf3. cytosolic dna also activates", "cytosolic dna also activates caspase", "dna also activates caspase 1", "also activates caspase 1 dependent", "activates caspase 1 dependent maturation", "caspase 1 dependent maturation of", "1 dependent maturation of the", "dependent maturation of the pro", "maturation of the pro inflammatory", "of the pro inflammatory cytokines", "the pro inflammatory cytokines interleukin", "pro inflammatory cytokines interleukin il", "inflammatory cytokines interleukin il 1beta", "cytokines interleukin il 1beta and", "interleukin il 1beta and il", "il 1beta and il 18.", "1beta and il 18. this", "and il 18. this pathway", "il 18. this pathway is", "18. this pathway is mediated", "this pathway is mediated by", "pathway is mediated by aim2." ] }, { "record_id": "GLY_000594_1_145", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1839117", "r hsa", "hsa 1839117", "r hsa 1839117" ] }, { "record_id": "GLY_000594_1_145", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by cytosolic", "cytosolic fgfr1", "fgfr1 fusion", "fusion mutants", "signaling by cytosolic", "by cytosolic fgfr1", "cytosolic fgfr1 fusion", "fgfr1 fusion mutants", "signaling by cytosolic fgfr1", "by cytosolic fgfr1 fusion", "cytosolic fgfr1 fusion mutants", "signaling by cytosolic fgfr1 fusion", "by cytosolic fgfr1 fusion mutants", "8p11 myeloproliferative", "myeloproliferative syndrome", "is an", "an aggressive", "aggressive disorder", "disorder that", "that is", "is associated", "associated with", "with a", "a translocation", "translocation event", "event at", "at the", "the fgfr1", "fgfr1 gene", "gene on", "on chromosome", "chromosome 8p11.", "typical symptoms", "symptoms upon", "upon diagnosis", "diagnosis include", "include eosinophilia", "eosinophilia and", "and associated", "associated t", "t cell", "cell lymphoblastic", "lymphoblastic lymphoma", "the disease", "disease rapidly", "rapidly advances", "advances to", "to acute", "acute leukemia", "usually of", "of myeloid", "myeloid lineage.", "at present", "present the", "the only", "only effective", "effective treatment", "treatment is", "is allogenic", "allogenic stem", "stem cell", "cell transplantation", "reviewed in", "in jackson", "2010 .", "

at the", "the molecular", "molecular level", "ems appears", "appears to", "to be", "be caused", "caused by", "by translocation", "translocation events", "events on", "chromosome 8", "8 that", "that create", "create gene", "gene fusions", "fusions between", "between the", "the intracellular", "intracellular domain", "domain of", "of fgfr1", "fgfr1 and", "and an", "an n", "n terminal", "terminal partner", "partner gene", "gene that", "that encodes", "encodes a", "a dimerization", "dimerization domain.", "the resulting", "resulting fusion", "fusion protein", "protein dimerizes", "dimerizes in", "in a", "a ligand", "ligand independent", "independent fashion", "fashion based", "based the", "the n", "terminal domain", "domain provided", "provided by", "by the", "the partner", "partner protein", "protein and", "and stimulates", "stimulates constititutive", "constititutive downstream", "downstream fgfr1", "fgfr1 signaling", "signaling without", "without altering", "altering the", "the intrisic", "intrisic kinase", "kinase activity", "activity of", "of the", "the receptor.", "to date", "11 partner", "partner genes", "genes have", "have been", "been identified:", "identified: zmym2", "myo18a and", "and cpsf6", "although not", "not all", "all have", "been functionally", "functionally characterized", "turner and", "and grose", "2011 .", "
where examined", "cell lines", "lines carrying", "carrying fgfr1", "fusion genes", "been shown", "shown to", "be transforming", "and to", "to support", "support il3", "il3 independent", "independent proliferation", "proliferation through", "through anti", "anti apoptotic", "prosurvival pathways", "pathways lelievre", "wasag 2011", "1999 .", "signaling appears", "to occur", "occur predominantly", "predominantly through", "through plcgamma", "pi3k and", "and stat", "stat signaling", "a more", "more minor", "minor contribution", "contribution from", "from mapk", "mapk activation.", "because the", "the fusion", "fusion proteins", "proteins lack", "lack the", "the frs2", "frs2 binding", "binding site", "the mechanism", "mechanism of", "of mapk", "mapk activation", "activation is", "is unclear.", "recruitment of", "grb2:sos1 through", "through recruitment", "of shc", "shc is", "is one", "one possibility", "2001 .", "8p11 myeloproliferative syndrome", "syndrome ems", "ems is", "is an aggressive", "an aggressive disorder", "aggressive disorder that", "disorder that is", "that is associated", "is associated with", "associated with a", "with a translocation", "a translocation event", "translocation event at", "event at the", "at the fgfr1", "the fgfr1 gene", "fgfr1 gene on", "gene on chromosome", "on chromosome 8p11.", "8p11. typical", "typical symptoms upon", "symptoms upon diagnosis", "upon diagnosis include", "diagnosis include eosinophilia", "include eosinophilia and", "eosinophilia and associated", "and associated t", "associated t cell", "t cell lymphoblastic", "cell lymphoblastic lymphoma", "lymphoma the", "the disease rapidly", "disease rapidly advances", "rapidly advances to", "advances to acute", "to acute leukemia", "leukemia usually", "usually of myeloid", "of myeloid lineage.", "lineage. at", "at present the", "present the only", "the only effective", "only effective treatment", "effective treatment is", "treatment is allogenic", "is allogenic stem", "allogenic stem cell", "stem cell transplantation", "transplantation reviewed", "reviewed in jackson", "jackson 2010", ".

at", "

at the molecular", "the molecular level", "level ems", "ems appears to", "appears to be", "to be caused", "be caused by", "caused by translocation", "by translocation events", "translocation events on", "events on chromosome", "on chromosome 8", "chromosome 8 that", "8 that create", "that create gene", "create gene fusions", "gene fusions between", "fusions between the", "between the intracellular", "the intracellular domain", "intracellular domain of", "domain of fgfr1", "of fgfr1 and", "fgfr1 and an", "and an n", "an n terminal", "n terminal partner", "terminal partner gene", "partner gene that", "gene that encodes", "that encodes a", "encodes a dimerization", "a dimerization domain.", "domain. the", "the resulting fusion", "resulting fusion protein", "fusion protein dimerizes", "protein dimerizes in", "dimerizes in a", "in a ligand", "a ligand independent", "ligand independent fashion", "independent fashion based", "fashion based the", "based the n", "the n terminal", "n terminal domain", "terminal domain provided", "domain provided by", "provided by the", "by the partner", "the partner protein", "partner protein and", "protein and stimulates", "and stimulates constititutive", "stimulates constititutive downstream", "constititutive downstream fgfr1", "downstream fgfr1 signaling", "fgfr1 signaling without", "signaling without altering", "without altering the", "altering the intrisic", "the intrisic kinase", "intrisic kinase activity", "kinase activity of", "activity of the", "of the receptor.", "receptor. to", "date 11", "11 partner genes", "partner genes have", "genes have been", "have been identified:", "been identified: zmym2", "zmym2 fgfr1op", "fgfr1op fgfr1op2", "fgfr1op2 hervk", "hervk trim24", "trim24 cux1", "cux1 bcr", "bcr cep110", "cep110 lrrfip1", "lrrfip1 myo18a", "myo18a and cpsf6", "cpsf6 although", "although not all", "not all have", "all have been", "have been functionally", "been functionally characterized", "characterized reviewed", "2010 turner", "turner and grose", "grose 2010", "2010 wesche", "wesche 2011", ".
where", "examined cell", "cell lines carrying", "lines carrying fgfr1", "carrying fgfr1 fusion", "fgfr1 fusion genes", "fusion genes have", "have been shown", "been shown to", "shown to be", "to be transforming", "transforming and", "and to support", "to support il3", "support il3 independent", "il3 independent proliferation", "independent proliferation through", "proliferation through anti", "through anti apoptotic", "apoptotic prosurvival", "prosurvival pathways lelievre", "lelievre 2008", "2008 ollendorff", "ollendorff 1999", "1999 chase", "chase 2007", "2007 guasch", "guasch 2001", "2001 wasag", "2011 roumiantsev", "roumiantsev 2004", "2004 demiroglu", "demiroglu 2001", "2001 smedley", "smedley 1999", ". signaling", "signaling appears to", "appears to occur", "to occur predominantly", "occur predominantly through", "predominantly through plcgamma", "plcgamma pi3k", "pi3k and stat", "and stat signaling", "signaling with", "with a more", "a more minor", "more minor contribution", "minor contribution from", "contribution from mapk", "from mapk activation.", "activation. because", "because the fusion", "the fusion proteins", "fusion proteins lack", "proteins lack the", "lack the frs2", "the frs2 binding", "frs2 binding site", "site the", "the mechanism of", "mechanism of mapk", "of mapk activation", "mapk activation is", "activation is unclear.", "unclear. recruitment", "of grb2:sos1", "grb2:sos1 through recruitment", "through recruitment of", "recruitment of shc", "of shc is", "shc is one", "is one possibility", "possibility guasch", "myeloproliferative syndrome ems", "ems is an", "is an aggressive disorder", "an aggressive disorder that", "aggressive disorder that is", "disorder that is associated", "that is associated with", "is associated with a", "associated with a translocation", "with a translocation event", "a translocation event at", "translocation event at the", "event at the fgfr1", "at the fgfr1 gene", "the fgfr1 gene on", "fgfr1 gene on chromosome", "gene on chromosome 8p11.", "chromosome 8p11. typical", "8p11. typical symptoms", "typical symptoms upon diagnosis", "symptoms upon diagnosis include", "upon diagnosis include eosinophilia", "diagnosis include eosinophilia and", "include eosinophilia and associated", "eosinophilia and associated t", "and associated t cell", "associated t cell lymphoblastic", "t cell lymphoblastic lymphoma", "lymphoblastic lymphoma the", "lymphoma the disease", "the disease rapidly advances", "disease rapidly advances to", "rapidly advances to acute", "advances to acute leukemia", "acute leukemia usually", "leukemia usually of", "usually of myeloid lineage.", "myeloid lineage. at", "lineage. at present", "at present the only", "present the only effective", "the only effective treatment", "only effective treatment is", "effective treatment is allogenic", "treatment is allogenic stem", "is allogenic stem cell", "allogenic stem cell transplantation", "cell transplantation reviewed", "transplantation reviewed in", "in jackson 2010", "jackson 2010 .", "2010 .

at", ".

at the", "

at the molecular level", "molecular level ems", "level ems appears", "ems appears to be", "appears to be caused", "to be caused by", "be caused by translocation", "caused by translocation events", "by translocation events on", "translocation events on chromosome", "events on chromosome 8", "on chromosome 8 that", "chromosome 8 that create", "8 that create gene", "that create gene fusions", "create gene fusions between", "gene fusions between the", "fusions between the intracellular", "between the intracellular domain", "the intracellular domain of", "intracellular domain of fgfr1", "domain of fgfr1 and", "of fgfr1 and an", "fgfr1 and an n", "and an n terminal", "an n terminal partner", "n terminal partner gene", "terminal partner gene that", "partner gene that encodes", "gene that encodes a", "that encodes a dimerization", "encodes a dimerization domain.", "dimerization domain. the", "domain. the resulting", "the resulting fusion protein", "resulting fusion protein dimerizes", "fusion protein dimerizes in", "protein dimerizes in a", "dimerizes in a ligand", "in a ligand independent", "a ligand independent fashion", "ligand independent fashion based", "independent fashion based the", "fashion based the n", "based the n terminal", "the n terminal domain", "n terminal domain provided", "terminal domain provided by", "domain provided by the", "provided by the partner", "by the partner protein", "the partner protein and", "partner protein and stimulates", "protein and stimulates constititutive", "and stimulates constititutive downstream", "stimulates constititutive downstream fgfr1", "constititutive downstream fgfr1 signaling", "downstream fgfr1 signaling without", "fgfr1 signaling without altering", "signaling without altering the", "without altering the intrisic", "altering the intrisic kinase", "the intrisic kinase activity", "intrisic kinase activity of", "kinase activity of the", "activity of the receptor.", "the receptor. to", "receptor. to date", "to date 11", "date 11 partner", "11 partner genes have", "partner genes have been", "genes have been identified:", "have been identified: zmym2", "identified: zmym2 fgfr1op", "lrrfip1 myo18a and", "and cpsf6 although", "cpsf6 although not", "although not all have", "not all have been", "all have been functionally", "have been functionally characterized", "functionally characterized reviewed", "characterized reviewed in", "2010 turner and", "and grose 2010", "wesche 2011 .", "2011 .
where", ".
where examined", "
where examined cell", "examined cell lines", "cell lines carrying fgfr1", "lines carrying fgfr1 fusion", "carrying fgfr1 fusion genes", "fgfr1 fusion genes have", "fusion genes have been", "genes have been shown", "have been shown to", "been shown to be", "shown to be transforming", "be transforming and", "transforming and to", "and to support il3", "to support il3 independent", "support il3 independent proliferation", "il3 independent proliferation through", "independent proliferation through anti", "proliferation through anti apoptotic", "anti apoptotic prosurvival", "apoptotic prosurvival pathways", "pathways lelievre 2008", "2001 wasag 2011", "wasag 2011 roumiantsev", "smedley 1999 .", "1999 . signaling", ". signaling appears", "signaling appears to occur", "appears to occur predominantly", "to occur predominantly through", "occur predominantly through plcgamma", "through plcgamma pi3k", "plcgamma pi3k and", "pi3k and stat signaling", "stat signaling with", "signaling with a", "with a more minor", "a more minor contribution", "more minor contribution from", "minor contribution from mapk", "contribution from mapk activation.", "mapk activation. because", "activation. because the", "because the fusion proteins", "the fusion proteins lack", "fusion proteins lack the", "proteins lack the frs2", "lack the frs2 binding", "the frs2 binding site", "binding site the", "site the mechanism", "the mechanism of mapk", "mechanism of mapk activation", "of mapk activation is", "mapk activation is unclear.", "is unclear. recruitment", "unclear. recruitment of", "recruitment of grb2:sos1", "of grb2:sos1 through", "grb2:sos1 through recruitment of", "through recruitment of shc", "recruitment of shc is", "of shc is one", "shc is one possibility", "one possibility guasch", "guasch 2001 .", "8p11 myeloproliferative syndrome ems", "syndrome ems is", "ems is an aggressive", "is an aggressive disorder that", "an aggressive disorder that is", "aggressive disorder that is associated", "disorder that is associated with", "that is associated with a", "is associated with a translocation", "associated with a translocation event", "with a translocation event at", "a translocation event at the", "translocation event at the fgfr1", "event at the fgfr1 gene", "at the fgfr1 gene on", "the fgfr1 gene on chromosome", "fgfr1 gene on chromosome 8p11.", "on chromosome 8p11. typical", "chromosome 8p11. typical symptoms", "8p11. typical symptoms upon", "typical symptoms upon diagnosis include", "symptoms upon diagnosis include eosinophilia", "upon diagnosis include eosinophilia and", "diagnosis include eosinophilia and associated", "include eosinophilia and associated t", "eosinophilia and associated t cell", "and associated t cell lymphoblastic", "associated t cell lymphoblastic lymphoma", "cell lymphoblastic lymphoma the", "lymphoblastic lymphoma the disease", "lymphoma the disease rapidly", "the disease rapidly advances to", "disease rapidly advances to acute", "rapidly advances to acute leukemia", "to acute leukemia usually", "acute leukemia usually of", "leukemia usually of myeloid", "of myeloid lineage. at", "myeloid lineage. at present", "lineage. at present the", "at present the only effective", "present the only effective treatment", "the only effective treatment is", "only effective treatment is allogenic", "effective treatment is allogenic stem", "treatment is allogenic stem cell", "is allogenic stem cell transplantation", "stem cell transplantation reviewed", "cell transplantation reviewed in", "transplantation reviewed in jackson", "reviewed in jackson 2010", "in jackson 2010 .", "2010 .

at the", ".

at the molecular", "the molecular level ems", "molecular level ems appears", "level ems appears to", "ems appears to be caused", "appears to be caused by", "to be caused by translocation", "be caused by translocation events", "caused by translocation events on", "by translocation events on chromosome", "translocation events on chromosome 8", "events on chromosome 8 that", "on chromosome 8 that create", "chromosome 8 that create gene", "8 that create gene fusions", "that create gene fusions between", "create gene fusions between the", "gene fusions between the intracellular", "fusions between the intracellular domain", "between the intracellular domain of", "the intracellular domain of fgfr1", "intracellular domain of fgfr1 and", "domain of fgfr1 and an", "of fgfr1 and an n", "fgfr1 and an n terminal", "and an n terminal partner", "an n terminal partner gene", "n terminal partner gene that", "terminal partner gene that encodes", "partner gene that encodes a", "gene that encodes a dimerization", "that encodes a dimerization domain.", "a dimerization domain. the", "dimerization domain. the resulting", "domain. the resulting fusion", "the resulting fusion protein dimerizes", "resulting fusion protein dimerizes in", "fusion protein dimerizes in a", "protein dimerizes in a ligand", "dimerizes in a ligand independent", "in a ligand independent fashion", "a ligand independent fashion based", "ligand independent fashion based the", "independent fashion based the n", "fashion based the n terminal", "based the n terminal domain", "the n terminal domain provided", "n terminal domain provided by", "terminal domain provided by the", "domain provided by the partner", "provided by the partner protein", "by the partner protein and", "the partner protein and stimulates", "partner protein and stimulates constititutive", "protein and stimulates constititutive downstream", "and stimulates constititutive downstream fgfr1", "stimulates constititutive downstream fgfr1 signaling", "constititutive downstream fgfr1 signaling without", "downstream fgfr1 signaling without altering", "fgfr1 signaling without altering the", "signaling without altering the intrisic", "without altering the intrisic kinase", "altering the intrisic kinase activity", "the intrisic kinase activity of", "intrisic kinase activity of the", "kinase activity of the receptor.", "of the receptor. to", "the receptor. to date", "to date 11 partner", "date 11 partner genes", "11 partner genes have been", "partner genes have been identified:", "genes have been identified: zmym2", "been identified: zmym2 fgfr1op", "zmym2 fgfr1op fgfr1op2", "fgfr1op fgfr1op2 hervk", "fgfr1op2 hervk trim24", "hervk trim24 cux1", "trim24 cux1 bcr", "cux1 bcr cep110", "bcr cep110 lrrfip1", "cep110 lrrfip1 myo18a", "lrrfip1 myo18a and cpsf6", "myo18a and cpsf6 although", "and cpsf6 although not", "cpsf6 although not all", "although not all have been", "not all have been functionally", "all have been functionally characterized", "been functionally characterized reviewed", "functionally characterized reviewed in", "characterized reviewed in jackson", "jackson 2010 turner", "2010 turner and grose", "turner and grose 2010", "grose 2010 wesche", "2010 wesche 2011", "2011 .
where examined", "
where examined cell lines", "examined cell lines carrying", "cell lines carrying fgfr1 fusion", "lines carrying fgfr1 fusion genes", "carrying fgfr1 fusion genes have", "fgfr1 fusion genes have been", "fusion genes have been shown", "genes have been shown to", "have been shown to be", "been shown to be transforming", "to be transforming and", "be transforming and to", "transforming and to support", "and to support il3 independent", "to support il3 independent proliferation", "support il3 independent proliferation through", "il3 independent proliferation through anti", "independent proliferation through anti apoptotic", "through anti apoptotic prosurvival", "anti apoptotic prosurvival pathways", "apoptotic prosurvival pathways lelievre", "prosurvival pathways lelievre 2008", "lelievre 2008 ollendorff", "2008 ollendorff 1999", "ollendorff 1999 chase", "1999 chase 2007", "chase 2007 guasch", "2007 guasch 2001", "guasch 2001 wasag", "2011 roumiantsev 2004", "roumiantsev 2004 demiroglu", "2004 demiroglu 2001", "demiroglu 2001 smedley", "2001 smedley 1999", "1999 . signaling appears", ". signaling appears to", "signaling appears to occur predominantly", "appears to occur predominantly through", "to occur predominantly through plcgamma", "predominantly through plcgamma pi3k", "through plcgamma pi3k and", "plcgamma pi3k and stat", "and stat signaling with", "stat signaling with a", "signaling with a more", "with a more minor contribution", "a more minor contribution from", "more minor contribution from mapk", "minor contribution from mapk activation.", "from mapk activation. because", "mapk activation. because the", "activation. because the fusion", "because the fusion proteins lack", "the fusion proteins lack the", "fusion proteins lack the frs2", "proteins lack the frs2 binding", "lack the frs2 binding site", "frs2 binding site the", "binding site the mechanism", "site the mechanism of", "the mechanism of mapk activation", "mechanism of mapk activation is", "of mapk activation is unclear.", "activation is unclear. recruitment", "is unclear. recruitment of", "recruitment of grb2:sos1 through", "of grb2:sos1 through recruitment", "grb2:sos1 through recruitment of shc", "through recruitment of shc is", "recruitment of shc is one", "of shc is one possibility", "is one possibility guasch", "possibility guasch 2001" ] }, { "record_id": "GLY_000594_1_146", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1855183", "r hsa", "hsa 1855183", "r hsa 1855183" ] }, { "record_id": "GLY_000594_1_146", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of ip2", "and ins", "ins in", "in the", "the cytosol", "synthesis of ip2", "ip2 ip", "ip and", "and ins in", "ins in the", "in the cytosol", "of ip2 ip", "ip and ins", "and ins in the", "ins in the cytosol", "synthesis of ip2 ip", "ip2 ip and", "ip and ins in", "and ins in the cytosol", "inositol phosphates", 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discovered pdgf", "discovered pdgf c", "pdgf c and", "c and pdgf", "and pdgf d.", "pdgf d. the", "d. the four", "the four pdgf", "four pdgf chains", "pdgf chains assemble", "chains assemble into", "assemble into disulphide", "into disulphide bonded", "disulphide bonded dimers", "bonded dimers via", "dimers via homo", "homo or", "heterodimerization and", "and five different", "five different dimeric", "different dimeric isoforms", "dimeric isoforms have", "isoforms have been", "have been described", "been described so", "described so far", "far pdgf", "aa pdgf", "ab pdgf", "bb pdgf", "pdgf cc and", "cc and pdgf", "and pdgf dd.", "pdgf dd. it", "dd. it is", "it is notable", "is notable that", "notable that no", "that no heterodimers", "no heterodimers involving", "heterodimers involving pdgf", "involving pdgf c", "and pdgf d", "pdgf d chains", "d chains have", "chains have been", "have been described.", "been described. pdgf", "described. pdgf exerts", "pdgf exerts its", "exerts its effects", "its effects by", "effects by binding", "by binding to", "to and", "activating two", "two protein tyrosine", "protein tyrosine kinase", "kinase ptk", "ptk receptors", "receptors alpha", "alpha and beta.", "and beta. these", "beta. these receptors", "these receptors dimerize", "receptors dimerize and", "dimerize and undergo", "and undergo autophosphorylation.", "undergo autophosphorylation. the", "autophosphorylation. the phosphorylation", "the phosphorylation sites", "phosphorylation sites then", "sites then attract", "then attract downstream", "attract downstream effectors", "downstream effectors to", "effectors to transduct", "to transduct the", "transduct the signal", "the signal into", "signal into the", "into the cell.", "platelet derived growth factor", "growth factor pdgf", "pdgf is a", "is a potent stimulator", "a potent stimulator of", "potent stimulator of growth", "stimulator of growth and", "of growth and motility", "growth and motility of", "and motility of connective", "motility of connective tissue", "of connective tissue cells", "connective tissue cells such", "tissue cells such as", "cells such as fibroblasts", "such as fibroblasts and", "as fibroblasts and smooth", "fibroblasts and smooth muscle", "and smooth muscle cells", "smooth muscle cells as", "muscle cells as well", "cells as well as", "as well as other", "well as other cells", "as other cells such", "other cells such as", "cells such as capillary", "such as capillary endothelial", "as capillary endothelial cells", "capillary endothelial cells and", "endothelial cells and neurons.the", "cells and neurons.the pdgf", "and neurons.the pdgf family", "neurons.the pdgf family of", "pdgf family of growth", "family of growth factors", "of growth factors is", "growth factors is composed", "factors is composed of", "is composed of four", "composed of four different", "of four different polypeptide", "four different polypeptide chains", "different polypeptide chains encoded", "polypeptide chains encoded by", "chains encoded by four", "encoded by four different", "by four different genes.", "four different genes. the", "different genes. the classical", "genes. the classical pdgf", "the classical pdgf chains", "pdgf chains pdgf", "chains pdgf a", "pdgf a and pdgf", "a and pdgf b", "pdgf b and", "b and more", "and more recently discovered", "more recently discovered pdgf", "recently discovered pdgf c", "discovered pdgf c and", "pdgf c and pdgf", "c and pdgf d.", "and pdgf d. the", "pdgf d. the four", "d. the four pdgf", "the four pdgf chains", "four pdgf chains assemble", "pdgf chains assemble into", "chains assemble into disulphide", "assemble into disulphide bonded", "into disulphide bonded dimers", "disulphide bonded dimers via", "bonded dimers via homo", "via homo or", "homo or heterodimerization", "or heterodimerization and", "heterodimerization and five", "and five different dimeric", "five different dimeric isoforms", "different dimeric isoforms have", "dimeric isoforms have been", "isoforms have been described", "have been described so", "been described so far", "so far pdgf", "far pdgf aa", "pdgf aa pdgf", "aa pdgf ab", "pdgf ab pdgf", "ab pdgf bb", "pdgf bb pdgf", "bb pdgf cc", "pdgf cc and pdgf", "cc and pdgf dd.", "and pdgf dd. it", "pdgf dd. it is", "dd. it is notable", "it is notable that", "is notable that no", "notable that no heterodimers", "that no heterodimers involving", "no heterodimers involving pdgf", "heterodimers involving pdgf c", "involving pdgf c and", "c and pdgf d", "and pdgf d chains", "pdgf d chains have", "d chains have been", "chains have been described.", "have been described. pdgf", "been described. pdgf exerts", "described. pdgf exerts its", "pdgf exerts its effects", "exerts its effects by", "its effects by binding", "effects by binding to", "binding to and", "to and activating", "and activating two", "activating two protein", "two protein tyrosine kinase", "tyrosine kinase ptk", "receptors alpha and", "alpha and beta. these", "and beta. these receptors", "beta. these receptors dimerize", "these receptors dimerize and", "receptors dimerize and undergo", "dimerize and undergo autophosphorylation.", "and undergo autophosphorylation. the", "undergo autophosphorylation. the phosphorylation", "autophosphorylation. the phosphorylation sites", "the phosphorylation sites then", "phosphorylation sites then attract", "sites then attract downstream", "then attract downstream effectors", "attract downstream effectors to", "downstream effectors to transduct", "effectors to transduct the", "to transduct the signal", "transduct the signal into", "the signal into the", "signal into the cell.", "derived growth factor pdgf", "factor pdgf is", "pdgf is a potent", "is a potent stimulator of", "a potent stimulator of growth", "potent stimulator of growth and", "stimulator of growth and motility", "of growth and motility of", "growth and motility of connective", "and motility of connective tissue", "motility of connective tissue cells", "of connective tissue cells such", "connective tissue cells such as", "tissue cells such as fibroblasts", "cells such as fibroblasts and", "such as fibroblasts and smooth", "as fibroblasts and smooth muscle", "fibroblasts and smooth muscle cells", "and smooth muscle cells as", "smooth muscle cells as well", "muscle cells as well as", "cells as well as other", "as well as other cells", "well as other cells such", "as other cells such as", "other cells such as capillary", "cells such as capillary endothelial", "such as capillary endothelial cells", "as capillary endothelial cells and", "capillary endothelial cells and neurons.the", "endothelial cells and neurons.the pdgf", "cells and neurons.the pdgf family", "and neurons.the pdgf family of", "neurons.the pdgf family of growth", "pdgf family of growth factors", "family of growth factors is", "of growth factors is composed", "growth factors is composed of", "factors is composed of four", "is composed of four different", "composed of four different polypeptide", "of four different polypeptide chains", "four different polypeptide chains encoded", "different polypeptide chains encoded by", "polypeptide chains encoded by four", "chains encoded by four different", "encoded by four different genes.", "by four different genes. the", "four different genes. the classical", "different genes. the classical pdgf", "genes. the classical pdgf chains", "classical pdgf chains pdgf", "pdgf chains pdgf a", "chains pdgf a and", "pdgf a and pdgf b", "and pdgf b and", "pdgf b and more", "b and more recently", "and more recently discovered pdgf", "more recently discovered pdgf c", "recently discovered pdgf c and", "discovered pdgf c and pdgf", "pdgf c and pdgf d.", "c and pdgf d. the", "and pdgf d. the four", "pdgf d. the four pdgf", "d. the four pdgf chains", "the four pdgf chains assemble", "four pdgf chains assemble into", "pdgf chains assemble into disulphide", "chains assemble into disulphide bonded", "assemble into disulphide bonded dimers", "into disulphide bonded dimers via", "disulphide bonded dimers via homo", "dimers via homo or", "via homo or heterodimerization", "or heterodimerization and five", "heterodimerization and five different", "and five different dimeric isoforms", "five different dimeric isoforms have", "different dimeric isoforms have been", "dimeric isoforms have been described", "isoforms have been described so", "have been described so far", "described so far pdgf", "so far pdgf aa", "pdgf aa pdgf ab", "pdgf ab pdgf bb", "pdgf bb pdgf cc", "bb pdgf cc and", "pdgf cc and pdgf dd.", "cc and pdgf dd. it", "and pdgf dd. it is", "pdgf dd. it is notable", "dd. it is notable that", "it is notable that no", "is notable that no heterodimers", "notable that no heterodimers involving", "that no heterodimers involving pdgf", "no heterodimers involving pdgf c", "heterodimers involving pdgf c and", "involving pdgf c and pdgf", "pdgf c and pdgf d", "c and pdgf d chains", "and pdgf d chains have", "pdgf d chains have been", "d chains have been described.", "chains have been described. pdgf", "have been described. pdgf exerts", "been described. pdgf exerts its", "described. pdgf exerts its effects", "pdgf exerts its effects by", "exerts its effects by binding", "its effects by binding to", "by binding to and", "binding to and activating", "and activating two protein", "activating two protein tyrosine", "protein tyrosine kinase ptk", "kinase ptk receptors", "ptk receptors alpha", "receptors alpha and beta.", "alpha and beta. these receptors", "and beta. these receptors dimerize", "beta. these receptors dimerize and", "these receptors dimerize and undergo", "receptors dimerize and undergo autophosphorylation.", "dimerize and undergo autophosphorylation. the", "and undergo autophosphorylation. the phosphorylation", "undergo autophosphorylation. the phosphorylation sites", "autophosphorylation. the phosphorylation sites then", "the phosphorylation sites then attract", "phosphorylation sites then attract downstream", "sites then attract downstream effectors", "then attract downstream effectors to", "attract downstream effectors to transduct", "downstream effectors to transduct the", "effectors to transduct the signal", "to transduct the signal into", "transduct the signal into the", "the signal into the cell." ] }, { "record_id": "GLY_000594_1_150", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "187577", "r hsa", "hsa 187577", "r hsa 187577" ] }, { "record_id": "GLY_000594_1_150", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "scf skp2", "mediated degradation", "degradation of", "of p27/p21", "skp2 mediated", "mediated degradation of", "degradation of p27/p21", "scf skp2 mediated", "skp2 mediated degradation", "mediated degradation of p27/p21", "scf skp2 mediated degradation", "skp2 mediated degradation of", "during g1", "the activity", "activity of", "of cyclin", "cyclin dependent", "dependent kinases", "is kept", "kept in", "in check", "check by", "by the", "the cdk", "cdk inhibitors", "p27 and", "and p21", "thereby preventing", "preventing premature", "premature entry", "entry into", "into s", "s phase", "see guardavaccaro", "guardavaccaro and", "and pagano", "2006 .", ". these", "these two", "two ckis", "ckis are", "are degraded", "degraded in", "in late", "late g1", "g1 phase", "phase by", "the ubiquitin", "ubiquitin pathway", "pagano et", "et al.", "bloom et", "involving the", "ubiquitin ligase", "ligase scf", "tsvetkov et", "carrano et", "sutterluty et", "bornstein et", "and the", "the cell", "cell cycle", "cycle regulatory", "regulatory protein", "protein cks1", "ganoth et", "spruck et", "et al", "al 2001", "2003 .", ". recognition", "recognition of", "of p27", "p27 by", "by scf", "and its", "its subsequent", "subsequent ubiquitination", "ubiquitination is", "is dependent", "dependent upon", "upon cyclin", "cyclin e/a:cdk2", "mediated phosphorylation", "phosphorylation at", "at thr", "thr 187", "187 of", "montagnoli et", "1999 .", ". there", "there is", "is evidence", "evidence that", "that cyclin", "cyclin a/b:cdk1", "a/b:cdk1 complexes", "complexes can", "can also", "also bind", "bind and", "and phosphorylate", "phosphorylate p27", "p27 on", "on th187", "nakayama et", "2004 .", ". degradation", "of polyubiquitinated", "polyubiquitinated p27", "the 26s", "26s proteasome", "proteasome promotes", "promotes the", "of cdks", "cdks in", "in driving", "driving cells", "cells into", "s phase.", "al 1999", ". the", "the mechanism", "mechanism of", "of scf", "of p21", "p21 is", "is similar", "similar to", "to that", "that of", "p27 in", "in terms", "terms of", "of its", "its requirements", "requirements for", "for the", "the presence", "presence of", "of cks1", "cks1 and", "and of", "of cdk2/cyclin", "cdk2/cyclin e/a", "al. 2003", "wang et", "2005 .", ". in", "in addition", "as observed", "observed for", "for p27", "p21 phosphorylation", "at a", "a specific", "specific site", "stimulates its", "its ubiquitination.", "ubiquitination. in", "in contrast", "contrast to", "to p27", "ubiquitination of", "p21 can", "can take", "take place", "place in", "in the", "the absence", "absence of", "of phosphorylation", "although with", "with less", "less efficiency", "p27/p21 continues", "continues from", "from late", "through m", "m phase.", "phase. during", "during g0", "g0 and", "and from", "from early", "early g1", "g1 to", "to g1/s", "skp2 is", "is degraded", "degraded by", "the anaphase", "anaphase promoting", "promoting complex/cyclosome", "complex/cyclosome and", "its activator", "activator cdh1", "apc/c cdh1", "bashir et", "wei et", "the tight", "tight regulation", "regulation of", "of apc/c", "activity ensures", "ensures the", "the timely", "elimination skp2", "skp2 and", "plays a", "a critical", "critical role", "role in", "in controlling", "controlling the", "g1/s transition.", "transition. apc/c", "becomes active", "active in", "late m", "m phase", "association of", "of unphosphorylated", "unphosphorylated cdh1", "cdh1 with", "with the", "the apc/c.", "apc/c. apc/c", "remains active", "active until", "until the", "the g1/s", "g1/s phase", "phase at", "at which", "which time", "time it", "it interacts", "interacts with", "inhibitory protein", "hsu et", "2002 .", "inhibition of", "activity results", "results in", "in an", "an accumulation", "accumulation of", "of cyclins", "which leads", "leads to", "to the", "phosphorylation and", "and consequently", "consequently to", "to a", "a further", "further inactivation", "inactivation of", "of cdh1", "cdh1 at", "at g1/s", "lukas et", "to make", "make the", "the inactivation", "cdh1 and", "its e2", "namely ubc10", "are eliminated", "eliminated in", "an auto", "auto ubiquitination", "ubiquitination event", "rape and", "and kirschner", ". at", "skp2 reaccumulates", "reaccumulates as", "as cdh1", "cdh1 is", "is inactivated", "thus allowing", "allowing the", "the ubiquitination", "p21 and", "and p27", "and resulting", "resulting in", "in a", "further increase", "increase in", "in cdk", "cdk activity.", "g1 the", "the activity of", "activity of cyclin", "of cyclin dependent", "cyclin dependent kinases", "kinases cdks", "cdks is", "is kept in", "kept in check", "in check by", "check by the", "by the cdk", "the cdk inhibitors", "inhibitors ckis", "ckis p27", "p27 and p21", "p21 thereby", "thereby preventing premature", "preventing premature entry", "premature entry into", "entry into s", "into s phase", "phase see", "see guardavaccaro and", "guardavaccaro and pagano", "pagano 2006", "2006 . these", ". these two", "these two ckis", "two ckis are", "ckis are degraded", "are degraded in", "degraded in late", "in late g1", "late g1 phase", "g1 phase by", "phase by the", "by the ubiquitin", "the ubiquitin pathway", "pathway pagano", "pagano et al.", "al. 1995", "1995 bloom", "bloom et al.", "2003 involving", "involving the ubiquitin", "the ubiquitin ligase", "ubiquitin ligase scf", "ligase scf skp2", "tsvetkov et al.", "al. 1999", "1999 carrano", "carrano et al.", "1999 sutterluty", "sutterluty et al.", "1999 bornstein", "bornstein et al.", "2003 and", "and the cell", "the cell cycle", "cell cycle regulatory", "cycle regulatory protein", "regulatory protein cks1", "cks1 ganoth", "ganoth et al.", "al. 2001", "2001 spruck", "spruck et al", "et al 2001", "2001 bornstein", "2003 . recognition", ". recognition of", "recognition of p27", "of p27 by", "p27 by scf", "by scf skp2", "and its subsequent", "its subsequent ubiquitination", "subsequent ubiquitination is", "ubiquitination is dependent", "is dependent upon", "dependent upon cyclin", "upon cyclin e/a:cdk2", "e/a:cdk2 mediated", "mediated phosphorylation at", "phosphorylation at thr", "at thr 187", "thr 187 of", "187 of p27", "p27 montagnoli", "montagnoli et al.", "1999 . there", ". there is", "there is evidence", "is evidence that", "evidence that cyclin", "that cyclin a/b:cdk1", "cyclin a/b:cdk1 complexes", "a/b:cdk1 complexes can", "complexes can also", "can also bind", "also bind and", "bind and phosphorylate", "and phosphorylate p27", "phosphorylate p27 on", "p27 on th187", "th187 nakayama", "nakayama et al.", "al. 2004", "2004 . degradation", ". degradation of", "degradation of polyubiquitinated", "of polyubiquitinated p27", "polyubiquitinated p27 by", "p27 by the", "by the 26s", "the 26s proteasome", "26s proteasome promotes", "proteasome promotes the", "promotes the activity", "activity of cdks", "of cdks in", "cdks in driving", "in driving cells", "driving cells into", "cells into s", "into s phase.", "phase. montagnoli", "1999 tsvetkov", "carrano et al", "et al 1999", "al 1999 .", "1999 . the", ". the mechanism", "the mechanism of", "mechanism of scf", "of scf skp2", "degradation of p21", "of p21 is", "p21 is similar", "is similar to", "similar to that", "to that of", "that of p27", "of p27 in", 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scf", "of p27/p21 continues", "p27/p21 continues from", "continues from late", "from late g1", "g1 through", "through m phase.", "m phase. during", "phase. during g0", "during g0 and", "g0 and from", "and from early", "from early g1", "early g1 to", "g1 to g1/s", "g1/s skp2", "skp2 is degraded", "is degraded by", "degraded by the", "by the anaphase", "the anaphase promoting", "anaphase promoting complex/cyclosome", "promoting complex/cyclosome and", "complex/cyclosome and its", "and its activator", "its activator cdh1", "cdh1 apc/c", "bashir et al", "al 2004", "2004 wei", "wei et al", "the tight regulation", "tight regulation of", "regulation of apc/c", "of apc/c cdh1", "cdh1 activity", "activity ensures the", "ensures the timely", "timely elimination", "elimination skp2 and", "and thus", "thus plays", "plays a critical", "a critical role", "critical role in", "role in controlling", "in controlling the", "g1/s transition. apc/c", "transition. apc/c cdh1", "cdh1 becomes", "becomes active in", "active in late", "in late m", "late m phase", "m phase by", "the association", "association of unphosphorylated", "of unphosphorylated cdh1", "unphosphorylated cdh1 with", "cdh1 with the", "with the apc/c.", "the apc/c. apc/c", "apc/c. apc/c cdh1", "cdh1 remains", "remains active until", "active until the", "until the g1/s", "the g1/s phase", "g1/s phase at", "phase at which", "at which time", "which time it", "time it interacts", "it interacts with", "interacts with the", "the inhibitory", "protein emi1", "emi1 hsu", "hsu et al.", "al. 2002", ". inhibition", "inhibition of apc/c", "activity results in", "results in an", "in an accumulation", "an accumulation of", "accumulation of cyclins", "cyclins which", "which leads to", "leads to the", "the phosphorylation", "phosphorylation and consequently", "and consequently to", "consequently to a", "to a further", "a further inactivation", "further inactivation of", "inactivation of cdh1", "of cdh1 at", "cdh1 at g1/s", "g1/s lukas", "lukas et al.", ". finally", "finally to", "to make the", "make the inactivation", "the inactivation of", "inactivation of apc/c", "cdh1 permanent", "permanent cdh1", "cdh1 and its", "and its e2", "e2 namely", "ubc10 are", "are eliminated in", "eliminated in an", "in an auto", "an auto ubiquitination", "auto ubiquitination event", "event listovsky", "listovsky et", "2004 rape", "rape and kirschner", "2004 . at", ". at g1/s", "skp2 reaccumulates as", "reaccumulates as cdh1", "as cdh1 is", "cdh1 is inactivated", "inactivated thus", "thus allowing the", "allowing the ubiquitination", "the ubiquitination of", "of p21 and", "p21 and p27", "and p27 and", "p27 and resulting", "and resulting in", "resulting in a", "in a further", "a further increase", "further increase in", "increase in cdk", "in cdk activity.", "during g1 the", "g1 the activity", "the activity of cyclin", "activity of cyclin dependent", "of cyclin dependent kinases", "dependent kinases cdks", "cdks is kept", "is kept in check", "kept in check by", "in check by the", "check by the cdk", "by the cdk inhibitors", "cdk inhibitors ckis", "ckis p27 and", "and p21 thereby", "p21 thereby preventing", "thereby preventing premature entry", "preventing premature entry into", "premature entry into s", "entry into s phase", "s phase see", "phase see guardavaccaro", "see guardavaccaro and pagano", "and pagano 2006", "pagano 2006 .", "2006 . these two", ". these two ckis", "these two ckis are", "two ckis are degraded", "ckis are degraded in", "are degraded in late", "degraded in late g1", "in late g1 phase", "late g1 phase by", "g1 phase by the", "phase by the ubiquitin", "by the ubiquitin pathway", "ubiquitin pathway pagano", "pathway pagano et", "et al. 1995", "1995 bloom et", "2003 involving the", "involving the ubiquitin ligase", "the ubiquitin ligase scf", "ubiquitin ligase scf skp2", "skp2 tsvetkov", "et al. 1999", "1999 carrano et", "1999 sutterluty et", "1999 bornstein et", "2003 and the", "and the cell cycle", "the cell cycle regulatory", "cell cycle regulatory protein", "cycle regulatory protein cks1", "protein cks1 ganoth", "cks1 ganoth et", "et al. 2001", "2001 spruck et", "spruck et al 2001", "al 2001 bornstein", "2001 bornstein et", "2003 . recognition of", ". recognition of p27", "recognition of p27 by", "of p27 by scf", "p27 by scf skp2", "scf skp2 and", "skp2 and its", "and its subsequent ubiquitination", "its subsequent ubiquitination is", "subsequent ubiquitination is dependent", "ubiquitination is dependent upon", "is dependent upon cyclin", "dependent upon cyclin e/a:cdk2", "cyclin e/a:cdk2 mediated", "e/a:cdk2 mediated phosphorylation", "mediated phosphorylation at thr", "phosphorylation at thr 187", "at thr 187 of", "thr 187 of p27", "of p27 montagnoli", "p27 montagnoli et", "al. 1999 .", "1999 . there is", ". there is evidence", "there is evidence that", "is evidence that cyclin", "evidence that cyclin a/b:cdk1", "that cyclin a/b:cdk1 complexes", "cyclin a/b:cdk1 complexes can", "a/b:cdk1 complexes can also", "complexes can also bind", "can also bind and", "also bind and phosphorylate", "bind and phosphorylate p27", "and phosphorylate p27 on", "phosphorylate p27 on th187", "on th187 nakayama", "th187 nakayama et", "et al. 2004", "al. 2004 .", "2004 . degradation of", ". degradation of polyubiquitinated", "degradation of polyubiquitinated p27", "of polyubiquitinated p27 by", "polyubiquitinated p27 by the", "p27 by the 26s", "by the 26s proteasome", "the 26s proteasome promotes", "26s proteasome promotes the", "proteasome promotes the activity", "promotes the activity of", "the activity of cdks", "activity of cdks in", "of cdks in driving", "cdks in driving cells", "in driving cells into", "driving cells into s", "cells into s phase.", "s phase. montagnoli", "phase. montagnoli et", "1999 tsvetkov et", "carrano et al 1999", "et al 1999 .", "al 1999 . the", "1999 . the mechanism", ". the mechanism of", "the mechanism of scf", "mechanism of scf skp2", "mediated degradation of p21", "degradation of p21 is", "of p21 is similar", "p21 is similar to", "is similar to that", "similar to that of", "to that of p27", "that of p27 in", "of p27 in terms", "p27 in terms of", "in terms of its", "terms of its requirements", "of its requirements for", "its requirements for the", "requirements for the presence", "for the presence of", "the presence of cks1", "presence of cks1 and", "of cks1 and of", "cks1 and of cdk2/cyclin", "and of cdk2/cyclin e/a", "cdk2/cyclin e/a bornstein", "e/a bornstein et", "bornstein et al. 2003", "al. 2003 wang", "2003 wang et", "et al. 2005", "al. 2005 .", "2005 . in addition", "in addition as", "addition as observed", "as observed for p27", "for p27 p21", "p27 p21 phosphorylation", "p21 phosphorylation at a", "phosphorylation at a specific", "at a specific site", "specific site ser130", "ser130 stimulates its", "stimulates its ubiquitination. in", "its ubiquitination. in contrast", "ubiquitination. in contrast to", "in contrast to p27", "to p27 however", "however ubiquitination of", "ubiquitination of p21 can", "of p21 can take", "p21 can take place", "can take place in", "take place in the", "place in the absence", "in the absence of", "the absence of phosphorylation", "of phosphorylation although", "phosphorylation although with", "although with less efficiency", "less efficiency bornstein", "efficiency bornstein et", "et al. 2003 .", "2003 . scf", ". scf skp2", "degradation of p27/p21 continues", "of p27/p21 continues from", "p27/p21 continues from late", "continues from late g1", "late g1 through", "g1 through m", "through m phase. during", "m phase. during g0", "phase. during g0 and", "during g0 and from", "g0 and from early", "and from early g1", "from early g1 to", "early g1 to g1/s", "to g1/s skp2", "g1/s skp2 is", "skp2 is degraded by", "is degraded by the", "degraded by the anaphase", "by the anaphase promoting", "the anaphase promoting complex/cyclosome", "anaphase promoting complex/cyclosome and", "promoting complex/cyclosome and its", "complex/cyclosome and its activator", "and its activator cdh1", "activator cdh1 apc/c", "cdh1 apc/c cdh1", "et al 2004", "2004 wei et", "al 2004 .", "2004 . the", ". the tight", "the tight regulation of", "tight regulation of apc/c", "regulation of apc/c cdh1", "apc/c cdh1 activity", "cdh1 activity ensures", "activity ensures the timely", "the timely elimination", "timely elimination skp2", "skp2 and thus", "thus plays a", "plays a critical role", "a critical role in", "critical role in controlling", "role in controlling the", "controlling the g1/s", "the g1/s transition.", "g1/s transition. apc/c cdh1", "apc/c cdh1 becomes", "cdh1 becomes active", "becomes active in late", "active in late m", "in late m phase", "late m phase by", "m phase by the", "by the association", "the association of", "association of unphosphorylated cdh1", "of unphosphorylated cdh1 with", "unphosphorylated cdh1 with the", "cdh1 with the apc/c.", "with the apc/c. apc/c", "the apc/c. apc/c cdh1", "apc/c cdh1 remains", "cdh1 remains active", "remains active until the", "active until the g1/s", "until the g1/s phase", "the g1/s phase at", "g1/s phase at which", "phase at which time", "at which time it", "which time it interacts", "time it interacts with", "it interacts with the", "with the inhibitory", "the inhibitory protein", "inhibitory protein emi1", "emi1 hsu et", "et al. 2002", "al. 2002 .", "2002 . inhibition", ". inhibition of", "inhibition of apc/c cdh1", "cdh1 activity results", "activity results in an", "results in an accumulation", "in an accumulation of", "an accumulation of cyclins", "of cyclins which", "cyclins which leads", "which leads to the", "to the phosphorylation", "the phosphorylation and", "phosphorylation and consequently to", "and consequently to a", "consequently to a further", "to a further inactivation", "a further inactivation of", "further inactivation of cdh1", "inactivation of cdh1 at", "of cdh1 at g1/s", "at g1/s lukas", "g1/s lukas et", "1999 . finally", "finally to make", "to make the inactivation", "make the inactivation of", "the inactivation of apc/c", "inactivation of apc/c cdh1", "apc/c cdh1 permanent", "permanent cdh1 and", "cdh1 and its e2", "its e2 namely", "e2 namely ubc10", "namely ubc10 are", "ubc10 are eliminated", "are eliminated in an", "eliminated in an auto", "in an auto ubiquitination", "an auto ubiquitination event", "ubiquitination event listovsky", "listovsky et al.", "2004 rape and", "kirschner 2004", "2004 . at g1/s", "at g1/s skp2", "g1/s skp2 reaccumulates", "skp2 reaccumulates as cdh1", "reaccumulates as cdh1 is", "as cdh1 is inactivated", "is inactivated thus", "inactivated thus allowing", "thus allowing the ubiquitination", "allowing the ubiquitination of", "the ubiquitination of p21", "ubiquitination of p21 and", "of p21 and p27", "p21 and p27 and", "and p27 and resulting", "p27 and resulting in", "and resulting in a", "resulting in a further", "in a further increase", "a further increase in", "further increase in cdk", "increase in cdk activity.", "during g1 the activity", "g1 the activity of", "the activity of cyclin dependent", "activity of cyclin dependent kinases", "cyclin dependent kinases cdks", "kinases cdks is", "cdks is kept in", "is kept in check by", "kept in check by the", "in check by the cdk", "check by the cdk inhibitors", "the cdk inhibitors ckis", "inhibitors ckis p27", "ckis p27 and p21", "p27 and p21 thereby", "and p21 thereby preventing", "p21 thereby preventing premature", "thereby preventing premature entry into", "preventing premature entry into s", "premature entry into s phase", "into s phase see", "s phase see guardavaccaro", "phase see guardavaccaro and", "guardavaccaro and pagano 2006", "and pagano 2006 .", "pagano 2006 . these", "2006 . these two ckis", ". these two ckis are", "these two ckis are degraded", "two ckis are degraded in", "ckis are degraded in late", "are degraded in late g1", "degraded in late g1 phase", "in late g1 phase by", "late g1 phase by the", "g1 phase by the ubiquitin", "phase by the ubiquitin pathway", "the ubiquitin pathway pagano", "ubiquitin pathway pagano et", "pathway pagano et al.", "pagano et al. 1995", "al. 1995 bloom", "1995 bloom et al.", "bloom et al. 2003", "al. 2003 involving", "2003 involving the ubiquitin", "involving the ubiquitin ligase scf", "the ubiquitin ligase scf skp2", "scf skp2 tsvetkov", "skp2 tsvetkov et", "tsvetkov et al. 1999", "al. 1999 carrano", "1999 carrano et al.", "carrano et al. 1999", "al. 1999 sutterluty", "1999 sutterluty et al.", "sutterluty et al. 1999", "al. 1999 bornstein", "1999 bornstein et al.", "al. 2003 and", "2003 and the cell", "and the cell cycle regulatory", "the cell cycle regulatory protein", "cell cycle regulatory protein cks1", "regulatory protein cks1 ganoth", "protein cks1 ganoth et", "cks1 ganoth et al.", "ganoth et al. 2001", "al. 2001 spruck", "2001 spruck et al", "et al 2001 bornstein", "al 2001 bornstein et", "2001 bornstein et al.", "al. 2003 . recognition", "2003 . recognition of p27", ". recognition of p27 by", "recognition of p27 by scf", "of p27 by scf skp2", "by scf skp2 and", "scf skp2 and its", "skp2 and its subsequent", "and its subsequent ubiquitination is", "its subsequent ubiquitination is dependent", "subsequent ubiquitination is dependent upon", "ubiquitination is dependent upon cyclin", "is dependent upon cyclin e/a:cdk2", "upon cyclin e/a:cdk2 mediated", "cyclin e/a:cdk2 mediated phosphorylation", "e/a:cdk2 mediated phosphorylation at", "mediated phosphorylation at thr 187", "phosphorylation at thr 187 of", "at thr 187 of p27", "187 of p27 montagnoli", "of p27 montagnoli et", "p27 montagnoli et al.", "montagnoli et al. 1999", "et al. 1999 .", "al. 1999 . there", "1999 . there is evidence", ". there is evidence that", "there is evidence that cyclin", "is evidence that cyclin a/b:cdk1", "evidence that cyclin a/b:cdk1 complexes", "that cyclin a/b:cdk1 complexes can", "cyclin a/b:cdk1 complexes can also", "a/b:cdk1 complexes can also bind", "complexes can also bind and", "can also bind and phosphorylate", "also bind and phosphorylate p27", "bind and phosphorylate p27 on", "and phosphorylate p27 on th187", "p27 on th187 nakayama", "on th187 nakayama et", "th187 nakayama et al.", "nakayama et al. 2004", "et al. 2004 .", "al. 2004 . degradation", "2004 . degradation of polyubiquitinated", ". degradation of polyubiquitinated p27", "degradation of polyubiquitinated p27 by", "of polyubiquitinated p27 by the", "polyubiquitinated p27 by the 26s", "p27 by the 26s proteasome", "by the 26s proteasome promotes", "the 26s proteasome promotes the", "26s proteasome promotes the activity", "proteasome promotes the activity of", "promotes the activity of cdks", "the activity of cdks in", "activity of cdks in driving", "of cdks in driving cells", "cdks in driving cells into", "in driving cells into s", "driving cells into s phase.", "into s phase. montagnoli", "s phase. montagnoli et", "phase. montagnoli et al.", "al. 1999 tsvetkov", "1999 tsvetkov et al.", "1999 carrano et al", "carrano et al 1999 .", "et al 1999 . the", "al 1999 . the mechanism", "1999 . the mechanism of", ". the mechanism of scf", "the mechanism of scf skp2", "of scf skp2 mediated", "mediated degradation of p21 is", "degradation of p21 is similar", "of p21 is similar to", "p21 is similar to that", "is similar to that of", "similar to that of p27", "to that of p27 in", "that of p27 in terms", "of p27 in terms of", "p27 in terms of its", "in terms of its requirements", "terms of its requirements for", "of its requirements for the", "its requirements for the presence", "requirements for the presence of", "for the presence of cks1", "the presence of cks1 and", "presence of cks1 and of", "of cks1 and of cdk2/cyclin", "cks1 and of cdk2/cyclin e/a", "of cdk2/cyclin e/a bornstein", "cdk2/cyclin e/a bornstein et", "e/a bornstein et al.", "et al. 2003 wang", "al. 2003 wang et", "2003 wang et al.", "wang et al. 2005", "et al. 2005 .", "al. 2005 . in", ". in addition as", "in addition as observed", "addition as observed for", "observed for p27 p21", "for p27 p21 phosphorylation", "p27 p21 phosphorylation at", "p21 phosphorylation at a specific", "phosphorylation at a specific site", "a specific site ser130", "site ser130 stimulates", "ser130 stimulates its ubiquitination.", "stimulates its ubiquitination. in contrast", "its ubiquitination. in contrast to", "ubiquitination. in contrast to p27", "contrast to p27 however", "p27 however ubiquitination", "however ubiquitination of p21", "ubiquitination of p21 can take", "of p21 can take place", "p21 can take place in", "can take place in the", "take place in the absence", "place in the absence of", "in the absence of phosphorylation", "absence of phosphorylation although", "of phosphorylation although with", "phosphorylation although with less", "with less efficiency bornstein", "less efficiency bornstein et", "efficiency bornstein et al.", "bornstein et al. 2003 .", "al. 2003 . scf", "2003 . scf skp2", "mediated degradation of p27/p21 continues", "degradation of p27/p21 continues from", "of p27/p21 continues from late", "p27/p21 continues from late g1", "from late g1 through", "late g1 through m", "g1 through m phase.", "through m phase. during g0", "m phase. during g0 and", "phase. during g0 and from", "during g0 and from early", "g0 and from early g1", "and from early g1 to", "from early g1 to g1/s", "g1 to g1/s skp2", "to g1/s skp2 is", "g1/s skp2 is degraded", "skp2 is degraded by the", "is degraded by the anaphase", "degraded by the anaphase promoting", "by the anaphase promoting complex/cyclosome", "the anaphase promoting complex/cyclosome and", "anaphase promoting complex/cyclosome and its", "promoting complex/cyclosome and its activator", "complex/cyclosome and its activator cdh1", "its activator cdh1 apc/c", "activator cdh1 apc/c cdh1", "cdh1 bashir", "bashir et al 2004", "al 2004 wei", "2004 wei et al", "wei et al 2004", "et al 2004 .", "2004 . the tight", ". the tight regulation", "the tight regulation of apc/c", "tight regulation of apc/c cdh1", "of apc/c cdh1 activity", "apc/c cdh1 activity ensures", "cdh1 activity ensures the", "ensures the timely elimination", "the timely elimination skp2", "timely elimination skp2 and", "elimination skp2 and thus", "and thus plays", "thus plays a critical", "plays a critical role in", "a critical role in controlling", "critical role in controlling the", "in controlling the g1/s", "controlling the g1/s transition.", "the g1/s transition. apc/c", "transition. apc/c cdh1 becomes", "apc/c cdh1 becomes active", "cdh1 becomes active in", "becomes active in late m", "active in late m phase", "in late m phase by", "late m phase by the", "phase by the association", "by the association of", "the association of unphosphorylated", "association of unphosphorylated cdh1 with", "of unphosphorylated cdh1 with the", "unphosphorylated cdh1 with the apc/c.", "cdh1 with the apc/c. apc/c", "with the apc/c. apc/c cdh1", "apc/c. apc/c cdh1 remains", "apc/c cdh1 remains active", "cdh1 remains active until", "remains active until the g1/s", "active until the g1/s phase", "until the g1/s phase at", "the g1/s phase at which", "g1/s phase at which time", "phase at which time it", "at which time it interacts", "which time it interacts with", "time it interacts with the", "interacts with the inhibitory", "with the inhibitory protein", "protein emi1 hsu", "emi1 hsu et al.", "hsu et al. 2002", "et al. 2002 .", "2002 . inhibition of", ". inhibition of apc/c", "apc/c cdh1 activity results", "cdh1 activity results in", "activity results in an accumulation", "results in an accumulation of", "in an accumulation of cyclins", "accumulation of cyclins which", "of cyclins which leads", "cyclins which leads to", "leads to the phosphorylation", "to the phosphorylation and", "the phosphorylation and consequently", "phosphorylation and consequently to a", "and consequently to a further", "consequently to a further inactivation", "to a further inactivation of", "a further inactivation of cdh1", "further inactivation of cdh1 at", "inactivation of cdh1 at g1/s", "cdh1 at g1/s lukas", "at g1/s lukas et", "g1/s lukas et al.", "lukas et al. 1999", ". finally to", "finally to make the", "to make the inactivation of", "make the inactivation of apc/c", "the inactivation of apc/c cdh1", "of apc/c cdh1 permanent", "cdh1 permanent cdh1", "permanent cdh1 and its", "and its e2 namely", "its e2 namely ubc10", "namely ubc10 are eliminated", "ubc10 are eliminated in", "are eliminated in an auto", "eliminated in an auto ubiquitination", "in an auto ubiquitination event", "auto ubiquitination event listovsky", "event listovsky et", "al. 2004 rape", "2004 rape and kirschner", "and kirschner 2004", "kirschner 2004 .", ". at g1/s skp2", "at g1/s skp2 reaccumulates", "g1/s skp2 reaccumulates as", "skp2 reaccumulates as cdh1 is", "reaccumulates as cdh1 is inactivated", "cdh1 is inactivated thus", "is inactivated thus allowing", "inactivated thus allowing the", "thus allowing the ubiquitination of", "allowing the ubiquitination of p21", "the ubiquitination of p21 and", "ubiquitination of p21 and p27", "of p21 and p27 and", "p21 and p27 and resulting", "and p27 and resulting in", "p27 and resulting in a", "and resulting in a further", "resulting in a further increase", "in a further increase in", "a further increase in cdk", "further increase in cdk activity." ] }, { "record_id": "GLY_000594_1_151", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "189200", "r hsa", "hsa 189200", "r hsa 189200" ] }, { "record_id": "GLY_000594_1_151", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cellular hexose", "hexose transport", "cellular hexose transport", "two gene", "gene families", "families are", "are responsible", "responsible for", "for glucose", "glucose transport", "transport in", "in humans.", "humans. slc2", "encoding gluts", "and slc5", "encoding sglts", "families mediate", "mediate glucose", "glucose absorption", "absorption in", "in the", "the small", "small intestine", "glucose reabsorption", "reabsorption in", "the kidney", "glucose uptake", "uptake by", "by the", "the brain", "brain across", "across the", "the blood", "blood brain", "brain barrier", "barrier and", "and glucose", "glucose release", "release by", "by all", "all cells", "cells in", "the body.", "body. glucose", "glucose is", "is taken", "taken up", "up from", "from interstitial", "interstitial fluid", "fluid by", "by a", "a passive", "facilitative transport", "transport driven", "driven by", "the diffusion", "diffusion gradient", "gradient of", "of glucose", "and other", "other sugars", "the plasma", "plasma membrane.", "membrane. this", "this process", "process is", "is mediated", "mediated by", "a family", "family of", "of na+", "na+ independent", "facilitative glucose", "glucose transporters", "encoded by", "the slc2a", "slc2a gene", "gene family", "zhao &", "& keating", "keating 2007", "wood &", "& trayhurn", "trayhurn 2003", "2003 .", ". there", "there are", "are 14", "14 members", "members belonging", "belonging to", "to this", "this family", "glut1 12", "14 and", "and hmit", "h+/myo inositol", "inositol symporter", ". the", "the glut", "glut family", "family can", "can be", "be subdivided", "subdivided into", "into three", "three subclasses", "i iii", "based on", "on sequence", "sequence similarity", "similarity and", "and characteristic", "characteristic sequence", "sequence motifs", "joost &", "& thorens", "thorens 2001", "2001 .

hexoses", "notably fructose", "and galactose", "generated in", "the lumen", "lumen of", "of the", "intestine by", "by breakdown", "breakdown of", "of dietary", "dietary carbohydrate", "carbohydrate are", "are taken", "up by", "by enterocytes", "enterocytes lining", "lining the", "the microvilli", "microvilli of", "intestine and", "and released", "released from", "from them", "them into", "into the", "the blood.", "blood. uptake", "uptake into", "into enterocytes", "enterocytes is", "by two", "two transporters", "transporters localized", "localized on", "on the", "the lumenal", "lumenal surfaces", "surfaces of", "the cells", "glucose and", "together with", "with sodium", "sodium ions", "and glut5", "fructose .", ". glut2", "the basolateral", "basolateral surfaces", "of enterocytes", "mediates the", "the release", "release of", "of these", "these hexoses", "hexoses into", "wright et", "et al.", "al. 2004", "2004 .", "glut2 may", "may also", "also play", "play a", "a role", "role in", "in hexose", "hexose uptake", "uptake from", "from the", "the gut", "gut lumen", "lumen into", "enterocytes when", "when the", "lumenal content", "content of", "of monosaccharides", "monosaccharides is", "is very", "very high", "kellet &", "& brot", "brot laroche", "laroche 2005", "glut5 mediates", "mediates fructose", "fructose uptake", "blood into", "into cells", "cells of", "the body", "notably hepatocytes.

cells", "hepatocytes.

cells take", "take up", "up glucose", "glucose by", "by facilitated", "facilitated diffusion", "via glucose", "associated with", "with the", "plasma membrane", "a reversible", "reversible reaction.", "reaction. four", "four tissue", "tissue specific", "specific glut", "glut isoforms", "isoforms are", "are known.", "known. glucose", "glucose in", "the cytosol", "cytosol is", "is phosphorylated", "phosphorylated by", "by tissue", "specific kinases", "kinases to", "to yield", "yield glucose", "glucose 6", "6 phosphate", "which cannot", "cannot cross", "cross the", "membrane because", "because of", "of its", "its negative", "negative charge.", "charge. in", "the liver", "this reaction", "reaction is", "is catalyzed", "catalyzed by", "by glucokinase", "glucokinase which", "which has", "has a", "a low", "low affinity", "affinity for", "km about", "about 10", "10 mm", "but is", "is not", "not inhibited", "inhibited by", "by glucose", "6 phosphate.", "phosphate. in", "in other", "other tissues", "by isoforms", "isoforms of", "of hexokinase.", "hexokinase. hexokinases", "hexokinases are", "are feedback", "feedback inhibited", "phosphate and", "and have", "have a", "a high", "high affinity", "about 0.1", "0.1 mm", "mm .", ". liver", "liver cells", "cells can", "can thus", "thus accumulate", "accumulate large", "large amounts", "amounts of", "phosphate but", "but only", "only when", "when blood", "blood glucose", "glucose concentrations", "concentrations are", "are high", "while most", "most other", "tissues can", "can take", "glucose even", "even when", "are low", "low but", "but cannot", "cannot accumulate", "accumulate much", "much intracellular", "intracellular glucose", "phosphate. these", "these differences", "differences are", "are consistent", "consistent with", "the view", "view that", "that that", "that the", "liver functions", "functions to", "to buffer", "buffer blood", "tissues take", "glucose to", "to meet", "meet immediate", "immediate metabolic", "metabolic needs.

glucose", "needs.

glucose 6", "6 phosphatase", "expressed in", "in liver", "liver and", "and kidney", "allows glucose", "phosphate generated", "generated by", "by gluconeogenesis", "both tissues", "and glycogen", "glycogen breakdown", "to leave", "leave the", "the cell.", "cell. the", "the absence", "absence of", "phosphatase from", "from other", "tissues makes", "makes glucose", "by these", "these tissues", "tissues essentially", "essentially irreversible", "that cells", "in these", "glucose for", "for local", "local metabolic", "metabolic use.

class", "use.

class ii", "ii facilitative", "facilitative transporters", "transporters consist", "consist of", "of glut5", "9 and", "and 11", "two gene families", "gene families are", "families are responsible", "are responsible for", "responsible for glucose", "for glucose transport", "glucose transport in", "transport in humans.", "in humans. slc2", "slc2 encoding", "gluts and", "slc5 encoding", "sglts families", "families mediate glucose", "mediate glucose absorption", "glucose absorption in", "absorption in the", "in the small", "the small intestine", "intestine glucose", "glucose reabsorption in", "reabsorption in the", "in the kidney", "kidney glucose", "glucose uptake by", "uptake by the", "by the brain", "the brain across", "brain across the", "across the blood", "the blood brain", "blood brain barrier", "brain barrier and", "barrier and glucose", "and glucose release", "glucose release by", "release by all", "by all cells", "all cells in", "cells in the", "in the body.", "the body. glucose", "body. glucose is", "glucose is taken", "is taken up", "taken up from", "up from interstitial", "from interstitial fluid", "interstitial fluid by", "fluid by a", "by a passive", "passive facilitative", "facilitative transport driven", "transport driven by", "driven by the", "by the diffusion", "the diffusion gradient", "diffusion gradient of", "gradient of glucose", "and other sugars", "sugars across", "across the plasma", "the plasma membrane.", "plasma membrane. this", "membrane. this process", "this process is", "process is mediated", "is mediated by", "mediated by a", "by a family", "a family of", "family of na+", "of na+ independent", "independent facilitative", "facilitative glucose transporters", "transporters gluts", "gluts encoded", "encoded by the", "by the slc2a", "the slc2a gene", "slc2a gene family", "family zhao", "zhao & keating", "& keating 2007", "2007 wood", "wood & trayhurn", "& trayhurn 2003", "trayhurn 2003 .", "2003 . there", ". there are", "there are 14", "are 14 members", "14 members belonging", "members belonging to", "belonging to this", "to this family", "family glut1", "12 14", "14 and hmit", "hmit h+/myo", "h+/myo inositol symporter", "symporter .", ". the glut", "the glut family", "glut family can", "family can be", "can be subdivided", "be subdivided into", "subdivided into three", "into three subclasses", "subclasses i", "iii based", "based on sequence", "on sequence similarity", "sequence similarity and", "similarity and characteristic", "and characteristic sequence", "characteristic sequence motifs", "motifs joost", "joost & thorens", "& thorens 2001", "thorens 2001 .

hexoses", ".

hexoses notably", "fructose glucose", "galactose generated", "generated in the", "in the lumen", "the lumen of", "lumen of the", "of the small", "small intestine by", "intestine by breakdown", "by breakdown of", "breakdown of dietary", "of dietary carbohydrate", "dietary carbohydrate are", "carbohydrate are taken", "are taken up", "taken up by", "up by enterocytes", "by enterocytes lining", "enterocytes lining the", "lining the microvilli", "the microvilli of", "microvilli of the", "small intestine and", "intestine and released", "and released from", "released from them", "from them into", "them into the", "into the blood.", "the blood. uptake", "blood. uptake into", "uptake into enterocytes", "into enterocytes is", "enterocytes is mediated", "mediated by two", "by two transporters", "two transporters localized", "transporters localized on", "localized on the", "on the lumenal", "the lumenal surfaces", "lumenal surfaces of", "surfaces of the", "of the cells", "cells sglt1", "sglt1 glucose", "glucose and galactose", "galactose together", "together with sodium", "with sodium ions", "ions and", "glut5 fructose", "fructose . glut2", "glut2 localized", "on the basolateral", "the basolateral surfaces", "basolateral surfaces of", "surfaces of enterocytes", "enterocytes mediates", "mediates the release", "the release of", "release of these", "of these hexoses", "these hexoses into", "hexoses into the", "into the blood", "blood wright", "wright et al.", "et al. 2004", "al. 2004 .", "2004 . glut2", ". glut2 may", "glut2 may also", "may also play", "also play a", "play a role", "a role in", "role in hexose", "in hexose uptake", "hexose uptake from", "uptake from the", "from the gut", "the gut lumen", "gut lumen into", "lumen into enterocytes", "into enterocytes when", "enterocytes when the", "when the lumenal", "the lumenal content", "lumenal content of", "content of monosaccharides", "of monosaccharides is", "monosaccharides is very", "is very high", "high kellet", "kellet & brot", "& brot laroche", "brot laroche 2005", "2005 and", "and glut5 mediates", "glut5 mediates fructose", "mediates fructose uptake", "fructose uptake from", "from the blood", "the blood into", "blood into cells", "into cells of", "cells of the", "of the body", "body notably", "notably hepatocytes.

cells take", "hepatocytes.

cells take up", "take up glucose", "up glucose by", "glucose by facilitated", "by facilitated diffusion", "diffusion via", "via glucose transporters", "gluts associated", "associated with the", "with the plasma", "the plasma membrane", "membrane a", "a reversible reaction.", "reversible reaction. four", "reaction. four tissue", "four tissue specific", "tissue specific glut", "specific glut isoforms", "glut isoforms are", "isoforms are known.", "are known. glucose", "known. glucose in", "glucose in the", "in the cytosol", "the cytosol is", "cytosol is phosphorylated", "is phosphorylated by", "phosphorylated by tissue", "by tissue specific", "tissue specific kinases", "specific kinases to", "kinases to yield", "to yield glucose", "yield glucose 6", "glucose 6 phosphate", "phosphate which", "which cannot cross", "cannot cross the", "cross the plasma", "plasma membrane because", "membrane because of", "because of its", "of its negative", "its negative charge.", "negative charge. in", "charge. in the", "in the liver", "liver this", "this reaction is", "reaction is catalyzed", "is catalyzed by", "catalyzed by glucokinase", "by glucokinase which", "glucokinase which has", "which has a", "has a low", "a low affinity", "low affinity for", "affinity for glucose", "glucose km", "km about 10", "about 10 mm", "mm but", "but is not", "is not inhibited", "not inhibited by", "inhibited by glucose", "by glucose 6", "glucose 6 phosphate.", "6 phosphate. in", "phosphate. in other", "in other tissues", "tissues this", "catalyzed by isoforms", "by isoforms of", "isoforms of hexokinase.", "of hexokinase. hexokinases", "hexokinase. hexokinases are", "hexokinases are feedback", "are feedback inhibited", "feedback inhibited by", "6 phosphate and", "phosphate and have", "and have a", "have a high", "a high affinity", "high affinity for", "km about 0.1", "about 0.1 mm", "0.1 mm .", "mm . liver", ". liver cells", "liver cells can", "cells can thus", "can thus accumulate", "thus accumulate large", "accumulate large amounts", "large amounts of", "amounts of glucose", "of glucose 6", "6 phosphate but", "phosphate but only", "but only when", "only when blood", "when blood glucose", "blood glucose concentrations", "glucose concentrations are", "concentrations are high", "high while", "while most other", "most other tissues", "other tissues can", "tissues can take", "can take up", "up glucose even", "glucose even when", "even when blood", "concentrations are low", "are low but", "low but cannot", "but cannot accumulate", "cannot accumulate much", "accumulate much intracellular", "much intracellular glucose", "intracellular glucose 6", "6 phosphate. these", "phosphate. these differences", "these differences are", "differences are consistent", "are consistent with", "consistent with the", "with the view", "the view that", "view that that", "that that the", "that the liver", "the liver functions", "liver functions to", "functions to buffer", "to buffer blood", "buffer blood glucose", "concentrations while", "other tissues take", "tissues take up", "up glucose to", "glucose to meet", "to meet immediate", "meet immediate metabolic", "immediate metabolic needs.

glucose", "metabolic needs.

glucose 6", "needs.

glucose 6 phosphatase", "phosphatase expressed", "expressed in liver", "in liver and", "liver and kidney", "kidney allows", "allows glucose 6", "6 phosphate generated", "phosphate generated by", "generated by gluconeogenesis", "gluconeogenesis both", "tissues and", "and glycogen breakdown", "breakdown liver", "liver to", "to leave the", "leave the cell.", "the cell. the", "cell. the absence", "the absence of", "absence of glucose", "glucose 6 phosphatase", "6 phosphatase from", "phosphatase from other", "from other tissues", "other tissues makes", "tissues makes glucose", "makes glucose uptake", "uptake by these", "by these tissues", "these tissues essentially", "tissues essentially irreversible", "irreversible consistent", "view that cells", "that cells in", "cells in these", "in these tissues", "these tissues take", "up glucose for", "glucose for local", "for local metabolic", "local metabolic use.

class", "metabolic use.

class ii", "use.

class ii facilitative", "ii facilitative transporters", "facilitative transporters consist", "transporters consist of", "consist of glut5", "glut5 7", "7 9", "9 and 11", "11 zhao", "two gene families are", "gene families are responsible", "families are responsible for", "are responsible for glucose", "responsible for glucose transport", "for glucose transport in", "glucose transport in humans.", "transport in humans. slc2", "humans. slc2 encoding", "slc2 encoding gluts", "encoding gluts and", "gluts and slc5", "and slc5 encoding", "slc5 encoding sglts", "encoding sglts families", "sglts families mediate", "families mediate glucose absorption", "mediate glucose absorption in", "glucose absorption in the", "absorption in the small", "in the small intestine", "small intestine glucose", "intestine glucose reabsorption", "glucose reabsorption in the", "reabsorption in the kidney", "the kidney glucose", "kidney glucose uptake", "glucose uptake by the", "uptake by the brain", "by the brain across", "the brain across the", "brain across the blood", "across the blood brain", "the blood brain barrier", "blood brain barrier and", "brain barrier and glucose", "barrier and glucose release", "and glucose release by", "glucose release by all", "release by all cells", "by all cells in", "all cells in the", "cells in the body.", "in the body. glucose", "the body. glucose is", "body. glucose is taken", "glucose is taken up", "is taken up from", "taken up from interstitial", "up from interstitial fluid", "from interstitial fluid by", "interstitial fluid by a", "fluid by a passive", "a passive facilitative", "passive facilitative transport", "facilitative transport driven by", "transport driven by the", "driven by the diffusion", "by the diffusion gradient", "the diffusion gradient of", "diffusion gradient of glucose", "of glucose and", "glucose and other", "other sugars across", "sugars across the", "across the plasma membrane.", "the plasma membrane. this", "plasma membrane. this process", "membrane. this process is", "this process is mediated", "process is mediated by", "is mediated by a", "mediated by a family", "by a family of", "a family of na+", "family of na+ independent", "na+ independent facilitative", "independent facilitative glucose", "glucose transporters gluts", "gluts encoded by", "encoded by the slc2a", "by the slc2a gene", "the slc2a gene family", "gene family zhao", "family zhao &", "zhao & keating 2007", "keating 2007 wood", "2007 wood &", "wood & trayhurn 2003", "& trayhurn 2003 .", "trayhurn 2003 . there", "2003 . there are", ". there are 14", "there are 14 members", "are 14 members belonging", "14 members belonging to", "members belonging to this", "belonging to this family", "this family glut1", "family glut1 12", "glut1 12 14", "12 14 and", "and hmit h+/myo", "hmit h+/myo inositol", "inositol symporter .", "symporter . the", ". the glut family", "the glut family can", "glut family can be", "family can be subdivided", "can be subdivided into", "be subdivided into three", "subdivided into three subclasses", "three subclasses i", "subclasses i iii", "i iii based", "iii based on", "based on sequence similarity", "on sequence similarity and", "sequence similarity and characteristic", "similarity and characteristic sequence", "and characteristic sequence motifs", "sequence motifs joost", "motifs joost &", "joost & thorens 2001", "& thorens 2001 .

hexoses", "2001 .

hexoses notably", ".

hexoses notably fructose", "notably fructose glucose", "and galactose generated", "galactose generated in", "generated in the lumen", "in the lumen of", "the lumen of the", "lumen of the small", "of the small intestine", "the small intestine by", "small intestine by breakdown", "intestine by breakdown of", "by breakdown of dietary", "breakdown of dietary carbohydrate", "of dietary carbohydrate are", "dietary carbohydrate are taken", "carbohydrate are taken up", "are taken up by", "taken up by enterocytes", "up by enterocytes lining", "by enterocytes lining the", "enterocytes lining the microvilli", "lining the microvilli of", "the microvilli of the", "microvilli of the small", "the small intestine and", "small intestine and released", "intestine and released from", "and released from them", "released from them into", "from them into the", "them into the blood.", "into the blood. uptake", "the blood. uptake into", "blood. uptake into enterocytes", "uptake into enterocytes is", "into enterocytes is mediated", "enterocytes is mediated by", "is mediated by two", "mediated by two transporters", "by two transporters localized", "two transporters localized on", "transporters localized on the", "localized on the lumenal", "on the lumenal surfaces", "the lumenal surfaces of", "lumenal surfaces of the", "surfaces of the cells", "the cells sglt1", "sglt1 glucose and", "and galactose together", "galactose together with", "together with sodium ions", "sodium ions and", "ions and glut5", "and glut5 fructose", "glut5 fructose .", ". glut2 localized", "glut2 localized on", "localized on the basolateral", "on the basolateral surfaces", "the basolateral surfaces of", "basolateral surfaces of enterocytes", "of enterocytes mediates", "enterocytes mediates the", "mediates the release of", "the release of these", "release of these hexoses", "of these hexoses into", "these hexoses into the", "hexoses into the blood", "the blood wright", "blood wright et", "wright et al. 2004", "et al. 2004 .", "al. 2004 . glut2", "2004 . glut2 may", ". glut2 may also", "glut2 may also play", "may also play a", "also play a role", "play a role in", "a role in hexose", "role in hexose uptake", "in hexose uptake from", "hexose uptake from the", "uptake from the gut", "from the gut lumen", "the gut lumen into", "gut lumen into enterocytes", "lumen into enterocytes when", "into enterocytes when the", "enterocytes when the lumenal", "when the lumenal content", "the lumenal content of", "lumenal content of monosaccharides", "content of monosaccharides is", "of monosaccharides is very", "monosaccharides is very high", "very high kellet", "high kellet &", "kellet & brot laroche", "& brot laroche 2005", "laroche 2005 and", "2005 and glut5", "and glut5 mediates fructose", "glut5 mediates fructose uptake", "mediates fructose uptake from", "fructose uptake from the", "uptake from the blood", "from the blood into", "the blood into cells", "blood into cells of", "into cells of the", "cells of the body", "the body notably", "body notably hepatocytes.

cells", "notably hepatocytes.

cells take up", "hepatocytes.

cells take up glucose", "take up glucose by", "up glucose by facilitated", "glucose by facilitated diffusion", "facilitated diffusion via", "diffusion via glucose", "gluts associated with", "associated with the plasma", "with the plasma membrane", "plasma membrane a", "membrane a reversible", "a reversible reaction. four", "reversible reaction. four tissue", "reaction. four tissue specific", "four tissue specific glut", "tissue specific glut isoforms", "specific glut isoforms are", "glut isoforms are known.", "isoforms are known. glucose", "are known. glucose in", "known. glucose in the", "glucose in the cytosol", "in the cytosol is", "the cytosol is phosphorylated", "cytosol is phosphorylated by", "is phosphorylated by tissue", "phosphorylated by tissue specific", "by tissue specific kinases", "tissue specific kinases to", "specific kinases to yield", "kinases to yield glucose", "to yield glucose 6", "yield glucose 6 phosphate", "6 phosphate which", "phosphate which cannot", "which cannot cross the", "cannot cross the plasma", "cross the plasma membrane", "the plasma membrane because", "plasma membrane because of", "membrane because of its", "because of its negative", "of its negative charge.", "its negative charge. in", "negative charge. in the", "charge. in the liver", "the liver this", "liver this reaction", "this reaction is catalyzed", "reaction is catalyzed by", "is catalyzed by glucokinase", "catalyzed by glucokinase which", "by glucokinase which has", "glucokinase which has a", "which has a low", "has a low affinity", "a low affinity for", "low affinity for glucose", "for glucose km", "glucose km about", "km about 10 mm", "10 mm but", "mm but is", "but is not inhibited", "is not inhibited by", "not inhibited by glucose", "inhibited by glucose 6", "by glucose 6 phosphate.", "glucose 6 phosphate. in", "6 phosphate. in other", "phosphate. in other tissues", "other tissues this", "tissues this reaction", "is catalyzed by isoforms", "catalyzed by isoforms of", "by isoforms of hexokinase.", "isoforms of hexokinase. hexokinases", "of hexokinase. hexokinases are", "hexokinase. hexokinases are feedback", "hexokinases are feedback inhibited", "are feedback inhibited by", "feedback inhibited by glucose", "by glucose 6 phosphate", "glucose 6 phosphate and", "6 phosphate and have", "phosphate and have a", "and have a high", "have a high affinity", "a high affinity for", "high affinity for glucose", "km about 0.1 mm", "about 0.1 mm .", "0.1 mm . liver", "mm . liver cells", ". liver cells can", "liver cells can thus", "cells can thus accumulate", "can thus accumulate large", "thus accumulate large amounts", "accumulate large amounts of", "large amounts of glucose", "amounts of glucose 6", "of glucose 6 phosphate", "glucose 6 phosphate but", "6 phosphate but only", "phosphate but only when", "but only when blood", "only when blood glucose", "when blood glucose concentrations", "blood glucose concentrations are", "glucose concentrations are high", "are high while", "high while most", "while most other tissues", "most other tissues can", "other tissues can take", "tissues can take up", "can take up glucose", "take up glucose even", "up glucose even when", "glucose even when blood", "even when blood glucose", "glucose concentrations are low", "concentrations are low but", "are low but cannot", "low but cannot accumulate", "but cannot accumulate much", "cannot accumulate much intracellular", "accumulate much intracellular glucose", "much intracellular glucose 6", "intracellular glucose 6 phosphate.", "glucose 6 phosphate. these", "6 phosphate. these differences", "phosphate. these differences are", "these differences are consistent", "differences are consistent with", "are consistent with the", "consistent with the view", "with the view that", "the view that that", "view that that the", "that that the liver", "that the liver functions", "the liver functions to", "liver functions to buffer", "functions to buffer blood", "to buffer blood glucose", "buffer blood glucose concentrations", "glucose concentrations while", "concentrations while most", "most other tissues take", "other tissues take up", "tissues take up glucose", "take up glucose to", "up glucose to meet", "glucose to meet immediate", "to meet immediate metabolic", "meet immediate metabolic needs.

glucose", "immediate metabolic needs.

glucose 6", "metabolic needs.

glucose 6 phosphatase", "6 phosphatase expressed", "phosphatase expressed in", "expressed in liver and", "in liver and kidney", "and kidney allows", "kidney allows glucose", "allows glucose 6 phosphate", "glucose 6 phosphate generated", "6 phosphate generated by", "phosphate generated by gluconeogenesis", "by gluconeogenesis both", "gluconeogenesis both tissues", "both tissues and", "tissues and glycogen", "glycogen breakdown liver", "liver to leave", "to leave the cell.", "leave the cell. the", "the cell. the absence", "cell. the absence of", "the absence of glucose", "absence of glucose 6", "of glucose 6 phosphatase", "glucose 6 phosphatase from", "6 phosphatase from other", "phosphatase from other tissues", "from other tissues makes", "other tissues makes glucose", "tissues makes glucose uptake", "makes glucose uptake by", "glucose uptake by these", "uptake by these tissues", "by these tissues essentially", "these tissues essentially irreversible", "essentially irreversible consistent", "irreversible consistent with", "the view that cells", "view that cells in", "that cells in these", "cells in these tissues", "in these tissues take", "these tissues take up", "take up glucose for", "up glucose for local", "glucose for local metabolic", "for local metabolic use.

class", "local metabolic use.

class ii", "metabolic use.

class ii facilitative", "use.

class ii facilitative transporters", "ii facilitative transporters consist", "facilitative transporters consist of", "transporters consist of glut5", "of glut5 7", "7 9 and", "and 11 zhao", "11 zhao &", "two gene families are responsible", "gene families are responsible for", "families are responsible for glucose", "are responsible for glucose transport", "responsible for glucose transport in", "for glucose transport in humans.", "glucose transport in humans. slc2", "in humans. slc2 encoding", "humans. slc2 encoding gluts", "encoding gluts and slc5", "and slc5 encoding sglts", "encoding sglts families mediate", "sglts families mediate glucose", "families mediate glucose absorption in", "mediate glucose absorption in the", "glucose absorption in the small", "absorption in the small intestine", "the small intestine glucose", "small intestine glucose reabsorption", "intestine glucose reabsorption in", "glucose reabsorption in the kidney", "in the kidney glucose", "the kidney glucose uptake", "kidney glucose uptake by", "glucose uptake by the brain", "uptake by the brain across", "by the brain across the", "the brain across the blood", "brain across the blood brain", "across the blood brain barrier", "the blood brain barrier and", "blood brain barrier and glucose", "brain barrier and glucose release", "barrier and glucose release by", "and glucose release by all", "glucose release by all cells", "release by all cells in", "by all cells in the", "all cells in the body.", "cells in the body. glucose", "in the body. glucose is", "the body. glucose is taken", "body. glucose is taken up", "glucose is taken up from", "is taken up from interstitial", "taken up from interstitial fluid", "up from interstitial fluid by", "from interstitial fluid by a", "interstitial fluid by a passive", "by a passive facilitative", "a passive facilitative transport", "passive facilitative transport driven", "facilitative transport driven by the", "transport driven by the diffusion", "driven by the diffusion gradient", "by the diffusion gradient of", "the diffusion gradient of glucose", "gradient of glucose and", "of glucose and other", "glucose and other sugars", "and other sugars across", "other sugars across the", "sugars across the plasma", "across the plasma membrane. this", "the plasma membrane. this process", "plasma membrane. this process is", "membrane. this process is mediated", "this process is mediated by", "process is mediated by a", "is mediated by a family", "mediated by a family of", "by a family of na+", "a family of na+ independent", "of na+ independent facilitative", "na+ independent facilitative glucose", "independent facilitative glucose transporters", "facilitative glucose transporters gluts", "transporters gluts encoded", "gluts encoded by the", "encoded by the slc2a gene", "by the slc2a gene family", "slc2a gene family zhao", "gene family zhao &", "family zhao & keating", "& keating 2007 wood", "keating 2007 wood &", "2007 wood & trayhurn", "wood & trayhurn 2003 .", "& trayhurn 2003 . there", "trayhurn 2003 . there are", "2003 . there are 14", ". there are 14 members", "there are 14 members belonging", "are 14 members belonging to", "14 members belonging to this", "members belonging to this family", "to this family glut1", "this family glut1 12", "glut1 12 14 and", "12 14 and hmit", "14 and hmit h+/myo", "and hmit h+/myo inositol", "hmit h+/myo inositol symporter", "h+/myo inositol symporter .", "inositol symporter . the", "symporter . the glut", ". the glut family can", "the glut family can be", "glut family can be subdivided", "family can be subdivided into", "can be subdivided into three", "be subdivided into three subclasses", "into three subclasses i", "three subclasses i iii", "i iii based on", "iii based on sequence", "based on sequence similarity and", "on sequence similarity and characteristic", "sequence similarity and characteristic sequence", "similarity and characteristic sequence motifs", "characteristic sequence motifs joost", "sequence motifs joost &", "motifs joost & thorens", "joost & thorens 2001 .

hexoses", "thorens 2001 .

hexoses notably", "2001 .

hexoses notably fructose", "fructose glucose and", "and galactose generated in", "galactose generated in the", "generated in the lumen of", "in the lumen of the", "the lumen of the small", "lumen of the small intestine", "of the small intestine by", "the small intestine by breakdown", "small intestine by breakdown of", "intestine by breakdown of dietary", "by breakdown of dietary carbohydrate", "breakdown of dietary carbohydrate are", "of dietary carbohydrate are taken", "dietary carbohydrate are taken up", "carbohydrate are taken up by", "are taken up by enterocytes", "taken up by enterocytes lining", "up by enterocytes lining the", "by enterocytes lining the microvilli", "enterocytes lining the microvilli of", "lining the microvilli of the", "the microvilli of the small", "microvilli of the small intestine", "of the small intestine and", "the small intestine and released", "small intestine and released from", "intestine and released from them", "and released from them into", "released from them into the", "from them into the blood.", "them into the blood. uptake", "into the blood. uptake into", "the blood. uptake into enterocytes", "blood. uptake into enterocytes is", "uptake into enterocytes is mediated", "into enterocytes is mediated by", "enterocytes is mediated by two", "is mediated by two transporters", "mediated by two transporters localized", "by two transporters localized on", "two transporters localized on the", "transporters localized on the lumenal", "localized on the lumenal surfaces", "on the lumenal surfaces of", "the lumenal surfaces of the", "lumenal surfaces of the cells", "of the cells sglt1", "cells sglt1 glucose", "sglt1 glucose and galactose", "glucose and galactose together", "and galactose together with", "galactose together with sodium", "with sodium ions and", "sodium ions and glut5", "and glut5 fructose .", "glut5 fructose . glut2", "fructose . glut2 localized", ". glut2 localized on", "glut2 localized on the", "localized on the basolateral surfaces", "on the basolateral surfaces of", "the basolateral surfaces of enterocytes", "surfaces of enterocytes mediates", "of enterocytes mediates the", "enterocytes mediates the release", "mediates the release of these", "the release of these hexoses", "release of these hexoses into", "of these hexoses into the", "these hexoses into the blood", "into the blood wright", "the blood wright et", "blood wright et al.", "wright et al. 2004 .", "et al. 2004 . glut2", "al. 2004 . glut2 may", "2004 . glut2 may also", ". glut2 may also play", "glut2 may also play a", "may also play a role", "also play a role in", "play a role in hexose", "a role in hexose uptake", "role in hexose uptake from", "in hexose uptake from the", "hexose uptake from the gut", "uptake from the gut lumen", "from the gut lumen into", "the gut lumen into enterocytes", "gut lumen into enterocytes when", "lumen into enterocytes when the", "into enterocytes when the lumenal", "enterocytes when the lumenal content", "when the lumenal content of", "the lumenal content of monosaccharides", "lumenal content of monosaccharides is", "content of monosaccharides is very", "of monosaccharides is very high", "is very high kellet", "very high kellet &", "high kellet & brot", "kellet & brot laroche 2005", "brot laroche 2005 and", "laroche 2005 and glut5", "2005 and glut5 mediates", "and glut5 mediates fructose uptake", "glut5 mediates fructose uptake from", "mediates fructose uptake from the", "fructose uptake from the blood", "uptake from the blood into", "from the blood into cells", "the blood into cells of", "blood into cells of the", "into cells of the body", "of the body notably", "the body notably hepatocytes.

cells", "body notably hepatocytes.

cells take", "notably hepatocytes.

cells take up glucose", "hepatocytes.

cells take up glucose by", "take up glucose by facilitated", "up glucose by facilitated diffusion", "by facilitated diffusion via", "facilitated diffusion via glucose", "diffusion via glucose transporters", "via glucose transporters gluts", "transporters gluts associated", "gluts associated with the", "associated with the plasma membrane", "the plasma membrane a", "plasma membrane a reversible", "membrane a reversible reaction.", "a reversible reaction. four tissue", "reversible reaction. four tissue specific", "reaction. four tissue specific glut", "four tissue specific glut isoforms", "tissue specific glut isoforms are", "specific glut isoforms are known.", "glut isoforms are known. glucose", "isoforms are known. glucose in", "are known. glucose in the", "known. glucose in the cytosol", "glucose in the cytosol is", "in the cytosol is phosphorylated", "the cytosol is phosphorylated by", "cytosol is phosphorylated by tissue", "is phosphorylated by tissue specific", "phosphorylated by tissue specific kinases", "by tissue specific kinases to", "tissue specific kinases to yield", "specific kinases to yield glucose", "kinases to yield glucose 6", "to yield glucose 6 phosphate", "glucose 6 phosphate which", "6 phosphate which cannot", "phosphate which cannot cross", "which cannot cross the plasma", "cannot cross the plasma membrane", "cross the plasma membrane because", "the plasma membrane because of", "plasma membrane because of its", "membrane because of its negative", "because of its negative charge.", "of its negative charge. in", "its negative charge. in the", "negative charge. in the liver", "in the liver this", "the liver this reaction", "liver this reaction is", "this reaction is catalyzed by", "reaction is catalyzed by glucokinase", "is catalyzed by glucokinase which", "catalyzed by glucokinase which has", "by glucokinase which has a", "glucokinase which has a low", "which has a low affinity", "has a low affinity for", "a low affinity for glucose", "affinity for glucose km", "for glucose km about", "glucose km about 10", "about 10 mm but", "10 mm but is", "mm but is not", "but is not inhibited by", "is not inhibited by glucose", "not inhibited by glucose 6", "inhibited by glucose 6 phosphate.", "by glucose 6 phosphate. in", "glucose 6 phosphate. in other", "6 phosphate. in other tissues", "in other tissues this", "other tissues this reaction", "tissues this reaction is", "reaction is catalyzed by isoforms", "is catalyzed by isoforms of", "catalyzed by isoforms of hexokinase.", "by isoforms of hexokinase. hexokinases", "isoforms of hexokinase. hexokinases are", "of hexokinase. hexokinases are feedback", "hexokinase. hexokinases are feedback inhibited", "hexokinases are feedback inhibited by", "are feedback inhibited by glucose", "feedback inhibited by glucose 6", "inhibited by glucose 6 phosphate", "by glucose 6 phosphate and", "glucose 6 phosphate and have", "6 phosphate and have a", "phosphate and have a high", "and have a high affinity", "have a high affinity for", "a high affinity for glucose", "glucose km about 0.1", "km about 0.1 mm .", "about 0.1 mm . liver", "0.1 mm . liver cells", "mm . liver cells can", ". liver cells can thus", "liver cells can thus accumulate", "cells can thus accumulate large", "can thus accumulate large amounts", "thus accumulate large amounts of", "accumulate large amounts of glucose", "large amounts of glucose 6", "amounts of glucose 6 phosphate", "of glucose 6 phosphate but", "glucose 6 phosphate but only", "6 phosphate but only when", "phosphate but only when blood", "but only when blood glucose", "only when blood glucose concentrations", "when blood glucose concentrations are", "blood glucose concentrations are high", "concentrations are high while", "are high while most", "high while most other", "while most other tissues can", "most other tissues can take", "other tissues can take up", "tissues can take up glucose", "can take up glucose even", "take up glucose even when", "up glucose even when blood", "glucose even when blood glucose", "even when blood glucose concentrations", "blood glucose concentrations are low", "glucose concentrations are low but", "concentrations are low but cannot", "are low but cannot accumulate", "low but cannot accumulate much", "but cannot accumulate much intracellular", "cannot accumulate much intracellular glucose", "accumulate much intracellular glucose 6", "much intracellular glucose 6 phosphate.", "intracellular glucose 6 phosphate. these", "glucose 6 phosphate. these differences", "6 phosphate. these differences are", "phosphate. these differences are consistent", "these differences are consistent with", "differences are consistent with the", "are consistent with the view", "consistent with the view that", "with the view that that", "the view that that the", "view that that the liver", "that that the liver functions", "that the liver functions to", "the liver functions to buffer", "liver functions to buffer blood", "functions to buffer blood glucose", "to buffer blood glucose concentrations", "blood glucose concentrations while", "glucose concentrations while most", "concentrations while most other", "while most other tissues take", "most other tissues take up", "other tissues take up glucose", "tissues take up glucose to", "take up glucose to meet", "up glucose to meet immediate", "glucose to meet immediate metabolic", "to meet immediate metabolic needs.

glucose", "meet immediate metabolic needs.

glucose 6", "immediate metabolic needs.

glucose 6 phosphatase", "needs.

glucose 6 phosphatase expressed", "6 phosphatase expressed in", "phosphatase expressed in liver", "expressed in liver and kidney", "liver and kidney allows", "and kidney allows glucose", "kidney allows glucose 6", "allows glucose 6 phosphate generated", "glucose 6 phosphate generated by", "6 phosphate generated by gluconeogenesis", "generated by gluconeogenesis both", "by gluconeogenesis both tissues", "both tissues and glycogen", "tissues and glycogen breakdown", "and glycogen breakdown liver", "breakdown liver to", "liver to leave the", "to leave the cell. the", "leave the cell. the absence", "the cell. the absence of", "cell. the absence of glucose", "the absence of glucose 6", "absence of glucose 6 phosphatase", "of glucose 6 phosphatase from", "glucose 6 phosphatase from other", "6 phosphatase from other tissues", "phosphatase from other tissues makes", "from other tissues makes glucose", "other tissues makes glucose uptake", "tissues makes glucose uptake by", "makes glucose uptake by these", "glucose uptake by these tissues", "uptake by these tissues essentially", "by these tissues essentially irreversible", "tissues essentially irreversible consistent", "essentially irreversible consistent with", "irreversible consistent with the", "with the view that cells", "the view that cells in", "view that cells in these", "that cells in these tissues", "cells in these tissues take", "in these tissues take up", "these tissues take up glucose", "tissues take up glucose for", "take up glucose for local", "up glucose for local metabolic", "glucose for local metabolic use.

class", "for local metabolic use.

class ii", "local metabolic use.

class ii facilitative", "metabolic use.

class ii facilitative transporters", "use.

class ii facilitative transporters consist", "ii facilitative transporters consist of", "facilitative transporters consist of glut5", "consist of glut5 7", "glut5 7 9", "7 9 and 11", "9 and 11 zhao", "and 11 zhao &", "11 zhao & keating" ] }, { "record_id": "GLY_000594_1_152", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "190840", "r hsa", "hsa 190840", "r hsa 190840" ] }, { "record_id": "GLY_000594_1_152", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "microtubule dependent", "dependent trafficking", "trafficking of", "of connexons", "connexons from", "from golgi", "golgi to", "to the", "the plasma", "plasma membrane", "microtubule dependent trafficking", "dependent trafficking of", "trafficking of connexons", "of connexons from", "connexons from golgi", "from golgi to", "golgi to the", "to the plasma", "the plasma membrane", "microtubule dependent trafficking of", "dependent trafficking of connexons", "trafficking of connexons from", "of connexons from golgi", "connexons from golgi to", "from golgi to the", "golgi to the plasma", "to the plasma membrane", "microtubule dependent trafficking of connexons", "dependent trafficking of connexons from", "trafficking of connexons from golgi", "of connexons from golgi to", "connexons from golgi to the", "from golgi to the plasma", "golgi to the plasma membrane", "through videomicroscopy", "a saltatory", "saltatory transport", "transport of", "of connexon", "connexon vesicles", "vesicles along", "along curvilinear", "curvilinear microtubules", "microtubules from", "from the", "the golgi", "membrane has", "has been", "been observed", "lauf et", "et al.", "2002 .", ". such", "such a", "a transport", "transport system", "system has", "been described", "described for", "for similar", "similar secretory", "secretory vesicles", "toomre et", "1999 .", "videomicroscopy a", "a saltatory transport", "saltatory transport of", "transport of connexon", "of connexon vesicles", "connexon vesicles along", "vesicles along curvilinear", "along curvilinear microtubules", "curvilinear microtubules from", "microtubules from the", "from the golgi", "the golgi to", "plasma membrane has", "membrane has been", "has been observed", "observed lauf", "lauf et al.", "al. 2002", "2002 . such", ". such a", "such a transport", "a transport system", "transport system has", "system has been", "has been described", "been described for", "described for similar", "for similar secretory", "similar secretory vesicles", "vesicles toomre", "toomre et al.", "al. 1999", "through videomicroscopy a", "videomicroscopy a saltatory", "a saltatory transport of", "saltatory transport of connexon", "transport of connexon vesicles", "of connexon vesicles along", "connexon vesicles along curvilinear", "vesicles along curvilinear microtubules", "along curvilinear microtubules from", "curvilinear microtubules from the", "microtubules from the golgi", "from the golgi to", "the golgi to the", "the plasma membrane has", "plasma membrane has been", "membrane has been observed", "been observed lauf", "observed lauf et", "et al. 2002", "al. 2002 .", "2002 . such a", ". such a transport", "such a transport system", "a transport system has", "transport system has been", "system has been described", "has been described for", "been described for similar", "described for similar secretory", "for similar secretory vesicles", "secretory vesicles toomre", "vesicles toomre et", "et al. 1999", "al. 1999 .", "through videomicroscopy a saltatory", "videomicroscopy a saltatory transport", "a saltatory transport of connexon", "saltatory transport of connexon vesicles", "transport of connexon vesicles along", "of connexon vesicles along curvilinear", "connexon vesicles along curvilinear microtubules", "vesicles along curvilinear microtubules from", "along curvilinear microtubules from the", "curvilinear microtubules from the golgi", "microtubules from the golgi to", "from the golgi to the", "the golgi to the plasma", "to the plasma membrane has", "the plasma membrane has been", "plasma membrane has been observed", "has been observed lauf", "been observed lauf et", "observed lauf et al.", "lauf et al. 2002", "et al. 2002 .", "al. 2002 . such", "2002 . such a transport", ". such a transport system", "such a transport system has", "a transport system has been", "transport system has been described", "system has been described for", "has been described for similar", "been described for similar secretory", "described for similar secretory vesicles", "similar secretory vesicles toomre", "secretory vesicles toomre et", "vesicles toomre et al.", "toomre et al. 1999", "et al. 1999 ." ] }, { "record_id": "GLY_000594_1_153", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "190861", "r hsa", "hsa 190861", "r hsa 190861" ] }, { "record_id": "GLY_000594_1_153", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gap junction", "junction assembly", "gap junction assembly", "the assembly", "assembly of", "of gap", "gap junctions", "junctions involves", "synthesis of", "of connexin", "connexin polypeptides", "polypeptides at", "at endoplasmic", "endoplasmic reticulum", "reticulum membranes", "oligomerization into", "into homomeric", "and heteromeric", "heteromeric gap", "junction connexons", "hemi channels", "passage through", "through the", "the golgi", "golgi stacks", "intracellular storage", "storage within", "within trans", "trans golgi", "golgi membranes", "trafficking along", "along microtubules", "insertion of", "of connexons", "connexons into", "into the", "the plasma", "plasma membrane", "lateral diffusion", "diffusion of", "connexons in", "in the", "aggregation of", "of individual", "individual gap", "junction channels", "channels into", "into plaques", "stabilization of", "of peripheral", "peripheral microtubule", "microtubule plus", "plus ends", "ends by", "by binding", "binding to", "to cx43", "cx43 based", "based gap", "see segretain", "segretain and", "and falk", "the assembly of", "assembly of gap", "of gap junctions", "gap junctions involves", "involves 1", "1 synthesis", "synthesis of connexin", "of connexin polypeptides", "connexin polypeptides at", "polypeptides at endoplasmic", "at endoplasmic reticulum", "endoplasmic reticulum membranes", "2 oligomerization", "oligomerization into homomeric", "homomeric and", "and heteromeric gap", "heteromeric gap junction", "gap junction connexons", "connexons hemi", "3 passage", "passage through the", "through the golgi", "the golgi stacks", "4 intracellular", "intracellular storage within", "storage within trans", "within trans golgi", "trans golgi membranes", "5 trafficking", "trafficking along microtubules", "6 insertion", "insertion of connexons", "of connexons into", "connexons into the", "into the plasma", "the plasma membrane", "7 lateral", "lateral diffusion of", "diffusion of connexons", "of connexons in", "connexons in the", "in the plasma", "8 aggregation", "aggregation of individual", "of individual gap", "individual gap junction", "gap junction channels", "junction channels into", "channels into plaques", "plaques and", "and 9", "9 stabilization", "stabilization of peripheral", "of peripheral microtubule", "peripheral microtubule plus", "microtubule plus ends", "plus ends by", "ends by binding", "by binding to", "binding to cx43", "to cx43 based", "cx43 based gap", "based gap junctions", "junctions see", "see segretain and", "segretain and falk", "falk 2004.", "the assembly of gap", "assembly of gap junctions", "of gap junctions involves", "junctions involves 1", "1 synthesis of", "synthesis of connexin polypeptides", "of connexin polypeptides at", "connexin polypeptides at endoplasmic", "polypeptides at endoplasmic reticulum", "at endoplasmic reticulum membranes", "membranes 2", "2 oligomerization into", "into 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"stabilization of peripheral microtubule", "of peripheral microtubule plus", "peripheral microtubule plus ends", "microtubule plus ends by", "plus ends by binding", "ends by binding to", "by binding to cx43", "binding to cx43 based", "to cx43 based gap", "cx43 based gap junctions", "gap junctions see", "junctions see segretain", "see segretain and falk", "and falk 2004.", "the assembly of gap junctions", "assembly of gap junctions involves", "gap junctions involves 1", "involves 1 synthesis", "1 synthesis of connexin", "synthesis of connexin polypeptides at", "of connexin polypeptides at endoplasmic", "connexin polypeptides at endoplasmic reticulum", "polypeptides at endoplasmic reticulum membranes", "reticulum membranes 2", "2 oligomerization into homomeric", "oligomerization into homomeric and", "into homomeric and heteromeric", "homomeric and heteromeric gap", "and heteromeric gap junction connexons", "gap junction connexons hemi", "junction connexons hemi channels", "channels 3", "3 passage through the", "passage through the golgi stacks", "golgi stacks 4", "4 intracellular storage within", "intracellular storage within trans golgi", "storage within trans golgi membranes", "golgi membranes 5", "5 trafficking along microtubules", "along microtubules 6", "6 insertion of connexons", "insertion of connexons into the", "of connexons into the plasma", "connexons into the plasma membrane", "plasma membrane 7", "7 lateral diffusion of", "lateral diffusion of connexons in", "diffusion of connexons in the", "of connexons in the plasma", "connexons in the plasma membrane", "plasma membrane 8", "8 aggregation of individual", "aggregation of individual gap junction", "of individual gap junction channels", "individual gap junction channels into", "gap junction channels into plaques", "channels into plaques and", "plaques and 9", "and 9 stabilization", "9 stabilization of peripheral", "stabilization of peripheral microtubule plus", "of peripheral microtubule plus ends", "peripheral microtubule plus ends by", "microtubule plus ends by binding", "plus ends by binding to", "ends by binding to cx43", "by binding to cx43 based", "binding to cx43 based gap", "to cx43 based gap junctions", "based gap junctions see", "gap junctions see segretain", "junctions see segretain and", "segretain and falk 2004." ] }, { "record_id": "GLY_000594_1_154", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1912408", "r hsa", "hsa 1912408", "r hsa 1912408" ] }, { "record_id": "GLY_000594_1_154", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pre notch", "notch transcription", "transcription and", "and translation", "pre notch transcription", "notch transcription and", "transcription and translation", "pre notch transcription and", "notch transcription and translation", "pre notch transcription and translation", "

in humans", "the notch", "notch protein", "protein family", "family has", "has four", "four members:", "members: notch1", "notch3 and", "and notch4.", "notch4. notch1", "notch1 protein", "protein was", "was identified", "identified first", "as the", "the product", "product of", "of a", "a chromosome", "chromosome 9", "9 gene", "gene translocated", "translocated in", "in t", "t cell", "cell acute", "acute lymphoblastic", "lymphoblastic leukemia", "leukemia that", "that was", "was homologous", "homologous to", "to drosophila", "drosophila notch", "ellisen et", "et al.", "al. 1991", "1991 .", ". at", "at the", "the same", "same time", "rat notch1", "notch1 was", "was cloned", "weinmaster et", "followed by", "by cloning", "cloning of", "of mouse", "mouse notch1", "named motch", "del amo", "amo et", "al. 1992", "1992 .", ". notch2", "notch2 protein", "protein is", "is the", "a gene", "gene on", "on chromosome", "chromosome 1", "larsson et", "al. 1994", "1994 .", "notch2 expression", "expression is", "is differentially", "differentially regulated", "regulated during", "during b", "b cell", "cell development", "bertrand et", "al. 2000", "2000 .", "notch2 mutations", "mutations are", "are a", "a rare", "rare cause", "cause of", "of alagille", "alagille syndrome", "mcdaniell et", "al. 2006", "2006 .", ". notch3", "notch3 is", "chromosome 19.", "19. notch3", "notch3 mutations", "are the", "the underlying", "underlying cause", "of cadasil", "cerebral arteriopathy", "arteriopathy with", "with subcortical", "subcortical infarcts", "infarcts and", "and leukoencephalopathy", "joutel et", "al. 1996", "1996 .", ". notch4", "the last", "last notch", "protein discovered", "chromosome 6", "li et", "al. 1998", "1998 .", ".

micrornas", "

micrornas play", "play an", "an important", "important negative", "negative role", "role in", "in translation", "translation and/or", "and/or stability", "stability of", "of notch", "notch mrnas.", "mrnas. micrornas", "micrornas mir", "mir 34", "mir 34a", "mir 34b", "34b and", "and mi", "mi r34c", "whose transcription", "transcription is", "is directly", "directly induced", "induced by", "by the", "the tumor", "tumor suppressor", "suppressor protein", "protein p53", "chang et", "al. 2007", "raver shapira", "shapira et", "he et", "corney et", "bind and", "and negatively", "negatively regulate", "regulate translation", "translation of", "of notch1", "notch1 mrna", "al. 2009", "pang et", "al. 2010", "ji et", "and notch2", "notch2 mrna", "2009 .", ". notch1", "mrna translation", "translation is", "is also", "also negatively", "negatively regulated", "regulated by", "by micrornas", "mir 200b", "200b and", "and mir", "mir 200c", "kong et", "as well", "well as", "as mir", "mir 449a", "mir 449b", "449b and", "mir 449c", "marcet et", "al. 2011", "2011 .", ". translation", "of notch3", "notch3 mrna", "mrna is", "is negatively", "mir 150", "ghisi et", "mir 206", "song et", "of notch4", "notch4 mrna", "mir 181c", "hashimoto et", "mir 302a", "costa et", ".

the", "

the notch2nl

", "notch homolog", "homolog 2", "2 n", "n terminal", "terminal like", "gene family", "family includes", "includes four", "four genes", "like a", "like b", "and notch2nlr", "like r", "which originated", "originated from", "from the", "the partial", "partial duplication", "duplication of", "of the", "the first", "first four", "four exons", "exons and", "and introns", "introns of", "the notch2", "notch2 gene", "gene and", "and function", "function to", "to modulate", "modulate notch", "notch signaling", "fiddes et", "al. 2018", "florio et", "suzuki et", "lodewijk et", "al. 2020", "2020 .

nascent", ".

nascent notch", "notch peptides", "peptides are", "are co", "co translationally", "translationally targeted", "targeted to", "to the", "the endoplasmic", "endoplasmic reticulum", "reticulum for", "for further", "further processing", "by modification", "modification in", "in the", "the golgi", "golgi apparatus", "before trafficking", "trafficking to", "the plasma", "plasma membrane.", "membrane. endoplasmic", "reticulum calcium", "calcium atpases", "positively regulate", "regulate notch", "notch trafficking", "possibly by", "by contributing", "contributing to", "to accurate", "accurate folding", "folding of", "notch precursors", "periz et", "al. 1999", "1999 .

", "humans the", "the notch protein", "notch protein family", "protein family has", "family has four", "has four members:", "four members: notch1", "notch1 notch2", "notch2 notch3", "notch3 and notch4.", "and notch4. notch1", "notch4. notch1 protein", "notch1 protein was", "protein was identified", "was identified first", "first as", "as the product", "the product of", "product of a", "of a chromosome", "a chromosome 9", "chromosome 9 gene", "9 gene translocated", "gene translocated in", "translocated in t", "in t cell", "t cell acute", "cell acute lymphoblastic", "acute lymphoblastic leukemia", "lymphoblastic leukemia that", "leukemia that was", "that was homologous", "was homologous to", "homologous to drosophila", "to drosophila notch", "notch ellisen", "ellisen et al.", "et al. 1991", "al. 1991 .", "1991 . at", ". at the", "at the same", "the same time", "time rat", "rat notch1 was", "notch1 was cloned", "cloned weinmaster", "weinmaster et al.", "followed by cloning", "by cloning of", "cloning of mouse", "of mouse notch1", "notch1 named", "motch del", "del amo et", "amo et al.", "et al. 1992", "al. 1992 .", "1992 . notch2", ". notch2 protein", "notch2 protein is", "protein is the", "is the product", "of a gene", "a gene on", "gene on chromosome", "on chromosome 1", "1 larsson", "larsson et al.", "et al. 1994", "al. 1994 .", "1994 . notch2", ". notch2 expression", "notch2 expression is", "expression is differentially", "is differentially regulated", "differentially regulated during", "regulated during b", "during b cell", "b cell development", "development bertrand", "bertrand et al.", "et al. 2000", "al. 2000 .", "2000 . notch2", ". notch2 mutations", "notch2 mutations are", "mutations are a", "are a rare", "a rare cause", "rare cause of", "cause of alagille", "of alagille syndrome", "syndrome mcdaniell", "mcdaniell et al.", "et al. 2006", "al. 2006 .", "2006 . notch3", ". notch3 is", "notch3 is the", "on chromosome 19.", "chromosome 19. notch3", "19. notch3 mutations", "notch3 mutations are", "mutations are the", "are the underlying", "the underlying cause", "underlying cause of", "cause of cadasil", "cadasil cerebral", "cerebral arteriopathy with", "arteriopathy with subcortical", "with subcortical infarcts", "subcortical infarcts and", "infarcts and leukoencephalopathy", "leukoencephalopathy joutel", "joutel et al.", "et al. 1996", "al. 1996 .", "1996 . notch4", "notch4 the", "the last notch", "last notch protein", "notch protein discovered", "discovered is", "on chromosome 6", "6 li", "li et al.", "et al. 1998", "al. 1998 .", "1998 .

micrornas", ".

micrornas play", "

micrornas play an", "play an important", "an important negative", "important negative role", "negative role in", "role in translation", "in translation and/or", "translation and/or stability", "and/or stability of", "stability of notch", "of notch mrnas.", "notch mrnas. micrornas", "mrnas. micrornas mir", "micrornas mir 34", "34 mir", "34a mir", "mir 34b and", "34b and mi", "and mi r34c", "whose transcription is", "transcription is directly", "is directly induced", "directly induced by", "induced by the", "by the tumor", "the tumor suppressor", "tumor suppressor protein", "suppressor protein p53", "p53 chang", "chang et al.", "et al. 2007", "2007 raver", "raver shapira et", "shapira et al.", "2007 he", "he et al.", "2007 corney", "corney et al.", "2007 bind", "bind and negatively", "and negatively regulate", "negatively regulate translation", "regulate translation of", "translation of notch1", "of notch1 mrna", "mrna li", "et al. 2009", "2009 pang", "pang et al.", "et al. 2010", "2010 ji", "ji et al.", "2009 and", "and notch2 mrna", "al. 2009 .", "2009 . notch1", ". notch1 mrna", "notch1 mrna translation", "mrna translation is", "translation is also", "is also negatively", "also negatively regulated", "negatively regulated by", "regulated by micrornas", "by micrornas mir", "micrornas mir 200b", "mir 200b and", "200b and mir", "and mir 200c", "200c kong", "kong et al.", "as well as", "well as mir", "as mir 449a", "449a mir", "mir 449b and", "449b and mir", "and mir 449c", "449c marcet", "marcet et al.", "et al. 2011", "al. 2011 .", "2011 . translation", ". translation of", "translation of notch3", "of notch3 mrna", "notch3 mrna is", "mrna is negatively", "is negatively regulated", "micrornas mir 150", "150 ghisi", "ghisi et al.", "2011 and", "and mir 206", "206 song", "song et al.", "2009 . translation", "translation of notch4", "of notch4 mrna", "notch4 mrna is", "micrornas mir 181c", "181c hashimoto", "hashimoto et al.", "2010 and", "and mir 302a", "302a costa", "costa et al.", "2009 .

the", ".

the notch2nl

", "notch2nl

notch", "notch homolog 2", "homolog 2 n", "2 n terminal", "n terminal like", "like gene", "gene family includes", "family includes four", "includes four genes", "genes notch2nla", "notch2nla notch", "terminal like a", "notch2nlb notch", "terminal like b", "notch2nlc notch", "notch2nlr notch", "terminal like r", "which originated from", "originated from the", "from the partial", "the partial duplication", "partial duplication of", "duplication of the", "of the first", "the first four", "first four exons", "four exons and", "exons and introns", "and introns of", "introns of the", "of the notch2", "the notch2 gene", "notch2 gene and", "gene and function", "and function to", "function to modulate", "to modulate notch", "modulate notch signaling", "signaling fiddes", "fiddes et al.", "et al. 2018", "2018 florio", "florio et al.", "2018 suzuki", "suzuki et al.", "2018 lodewijk", "lodewijk et al.", "et al. 2020", "al. 2020 .

nascent", "2020 .

nascent notch", ".

nascent notch peptides", "notch peptides are", "peptides are co", "are co translationally", "co translationally targeted", "translationally targeted to", "targeted to the", "to the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum for", "reticulum for further", "for further processing", "processing followed", "followed by modification", "by modification in", "modification in the", "in the golgi", "the golgi apparatus", "apparatus before", "before trafficking to", "trafficking to the", "to the plasma", "the plasma membrane.", "plasma membrane. endoplasmic", "membrane. endoplasmic reticulum", "endoplasmic reticulum calcium", "reticulum calcium atpases", "atpases positively", "positively regulate notch", "regulate notch trafficking", "trafficking possibly", "possibly by contributing", "by contributing to", "contributing to accurate", "to accurate folding", "accurate folding of", "folding of notch", "of notch precursors", "precursors periz", "periz et al.", "et al. 1999", "al. 1999 .

", "

in humans the", "humans the notch", "the notch protein family", "notch protein family has", "protein family has four", "family has four members:", "has four members: notch1", "members: notch1 notch2", "notch2 notch3 and", "notch3 and notch4. notch1", "and notch4. notch1 protein", "notch4. notch1 protein was", "notch1 protein was identified", "protein was identified first", "identified first as", "first as the", "as the product of", "the product of a", "product of a chromosome", "of a chromosome 9", "a chromosome 9 gene", "chromosome 9 gene translocated", "9 gene translocated in", "gene translocated in t", "translocated in t cell", "in t cell acute", "t cell acute lymphoblastic", "cell acute lymphoblastic leukemia", "acute lymphoblastic leukemia that", "lymphoblastic leukemia that was", "leukemia that was homologous", "that was homologous to", "was homologous to drosophila", "homologous to drosophila notch", "drosophila notch ellisen", "notch ellisen et", "ellisen et al. 1991", "et al. 1991 .", "al. 1991 . at", "1991 . at the", ". at the same", "at the same time", "same time rat", "time rat notch1", "rat notch1 was cloned", "was cloned weinmaster", "cloned weinmaster et", "weinmaster et al. 1991", "1991 followed", "followed by cloning of", "by cloning of mouse", "cloning of mouse notch1", "mouse notch1 named", "notch1 named motch", "named motch del", "motch del amo", "del amo et al.", "amo et al. 1992", "et al. 1992 .", "al. 1992 . notch2", "1992 . notch2 protein", ". notch2 protein is", "notch2 protein is the", "protein is the product", "is the product of", "product of a gene", "of a gene on", "a gene on chromosome", "gene on chromosome 1", "chromosome 1 larsson", "1 larsson et", "larsson et al. 1994", "et al. 1994 .", "al. 1994 . notch2", "1994 . notch2 expression", ". notch2 expression is", "notch2 expression is differentially", "expression is differentially regulated", "is differentially regulated during", "differentially regulated during b", "regulated during b cell", "during b cell development", "cell development bertrand", "development bertrand et", "bertrand et al. 2000", "et al. 2000 .", "al. 2000 . notch2", "2000 . notch2 mutations", ". notch2 mutations are", "notch2 mutations are a", "mutations are a rare", "are a rare cause", "a rare cause of", "rare cause of alagille", "cause of alagille syndrome", "alagille syndrome mcdaniell", "syndrome mcdaniell et", "mcdaniell et al. 2006", "et al. 2006 .", "al. 2006 . notch3", "2006 . notch3 is", ". notch3 is the", "notch3 is the product", "gene on chromosome 19.", "on chromosome 19. notch3", "chromosome 19. notch3 mutations", "19. notch3 mutations are", "notch3 mutations are the", "mutations are the underlying", "are the underlying cause", "the underlying cause of", "underlying cause of cadasil", "of cadasil cerebral", "cadasil cerebral arteriopathy", "cerebral arteriopathy with subcortical", "arteriopathy with subcortical infarcts", "with subcortical infarcts and", "subcortical infarcts and leukoencephalopathy", "and leukoencephalopathy joutel", "leukoencephalopathy joutel et", "joutel et al. 1996", "et al. 1996 .", "al. 1996 . notch4", ". notch4 the", "notch4 the last", "the last notch protein", "last notch protein discovered", "protein discovered is", "discovered is the", "gene on chromosome 6", "chromosome 6 li", "6 li et", "li et al. 1998", "et al. 1998 .", "al. 1998 .

micrornas", "1998 .

micrornas play", ".

micrornas play an", "

micrornas play an important", "play an important negative", "an important negative role", "important negative role in", "negative role in translation", "role in translation and/or", "in translation and/or stability", "translation and/or stability of", "and/or stability of notch", "stability of notch mrnas.", "of notch mrnas. micrornas", "notch mrnas. micrornas mir", "mrnas. micrornas mir 34", "mir 34 mir", "34 mir 34a", "mir 34a mir", "34a mir 34b", "mir 34b and mi", "34b and mi r34c", "r34c whose", "whose transcription is directly", "transcription is directly induced", "is directly induced by", "directly induced by the", "induced by the tumor", "by the tumor suppressor", "the tumor suppressor protein", "tumor suppressor protein p53", "protein p53 chang", "p53 chang et", "chang et al. 2007", "al. 2007 raver", "2007 raver shapira", "raver shapira et al.", "shapira et al. 2007", "al. 2007 he", "2007 he et", "he et al. 2007", "al. 2007 corney", "2007 corney et", "corney et al. 2007", "al. 2007 bind", "2007 bind and", "bind and negatively regulate", "and negatively regulate translation", "negatively regulate translation of", "regulate translation of notch1", "translation of notch1 mrna", "notch1 mrna li", "mrna li et", "li et al. 2009", "al. 2009 pang", "2009 pang et", "pang et al. 2010", "al. 2010 ji", "2010 ji et", "ji et al. 2009", "al. 2009 and", "2009 and notch2", "notch2 mrna li", "et al. 2009 .", "al. 2009 . notch1", "2009 . notch1 mrna", ". notch1 mrna translation", "notch1 mrna translation is", "mrna translation is also", "translation is also negatively", "is also negatively regulated", "also negatively regulated by", "negatively regulated by micrornas", "regulated by micrornas mir", "by micrornas mir 200b", "micrornas mir 200b and", "mir 200b and mir", "200b and mir 200c", "mir 200c kong", "200c kong et", "kong et al. 2010", "2010 as", "as well as mir", "well as mir 449a", "mir 449a mir", "449a mir 449b", "mir 449b and mir", "449b and mir 449c", "mir 449c marcet", "449c marcet et", "marcet et al. 2011", "et al. 2011 .", "al. 2011 . translation", "2011 . translation of", ". translation of notch3", "translation of notch3 mrna", "of notch3 mrna is", "notch3 mrna is negatively", "mrna is negatively regulated", "is negatively regulated by", "by micrornas mir 150", "mir 150 ghisi", "150 ghisi et", "ghisi et al. 2011", "al. 2011 and", "2011 and mir", "mir 206 song", "206 song et", "song et al. 2009", "al. 2009 . translation", "2009 . translation of", ". translation of notch4", "translation of notch4 mrna", "of notch4 mrna is", "notch4 mrna is negatively", "by micrornas mir 181c", "mir 181c hashimoto", "181c hashimoto et", "hashimoto et al. 2010", "al. 2010 and", "2010 and mir", "mir 302a costa", "302a costa et", "costa et al. 2009", "al. 2009 .

the", "2009 .

the notch2nl

", "

the notch2nl

notch", "notch2nl

notch homolog", "notch homolog 2 n", "homolog 2 n terminal", "2 n terminal like", "terminal like gene", "like gene family", "gene family includes four", "family includes four genes", "four genes notch2nla", "notch2nla notch homolog", "n terminal like a", "a notch2nlb", "notch2nlb notch homolog", "n terminal like b", "b notch2nlc", "notch2nlc notch homolog", "like and", "and notch2nlr notch", "notch2nlr notch homolog", "n terminal like r", "r which", "which originated from the", "originated from the partial", "from the partial duplication", "the partial duplication of", "partial duplication of the", "duplication of the first", "of the first four", "the first four exons", "first four exons and", "four exons and introns", "exons and introns of", "and introns of the", "introns of the notch2", "of the notch2 gene", "the notch2 gene and", "notch2 gene and function", "gene and function to", "and function to modulate", "function to modulate notch", "to modulate notch signaling", "notch signaling fiddes", "signaling fiddes et", "fiddes et al. 2018", "al. 2018 florio", "2018 florio et", "florio et al. 2018", "al. 2018 suzuki", "2018 suzuki et", "suzuki et al. 2018", "al. 2018 lodewijk", "2018 lodewijk et", "lodewijk et al. 2020", "et al. 2020 .

nascent", "al. 2020 .

nascent notch", "2020 .

nascent notch peptides", ".

nascent notch peptides are", "notch peptides are co", "peptides are co translationally", "are co translationally targeted", "co translationally targeted to", "translationally targeted to the", "targeted to the endoplasmic", "to the endoplasmic reticulum", "the endoplasmic reticulum for", "endoplasmic reticulum for further", "reticulum for further processing", "further processing followed", "processing followed by", "followed by modification in", "by modification in the", "modification in the golgi", "in the golgi apparatus", "golgi apparatus before", "apparatus before trafficking", "before trafficking to the", "trafficking to the plasma", "to the plasma membrane.", "the plasma membrane. endoplasmic", "plasma membrane. endoplasmic reticulum", "membrane. endoplasmic reticulum calcium", "endoplasmic reticulum calcium atpases", "calcium atpases positively", "atpases positively regulate", "positively regulate notch trafficking", "notch trafficking possibly", "trafficking possibly by", "possibly by contributing to", "by contributing to accurate", "contributing to accurate folding", "to accurate folding of", "accurate folding of notch", "folding of notch precursors", "notch precursors periz", "precursors periz et", "periz et al. 1999", "et al. 1999 .

", "

in humans the notch", "humans the notch protein", "the notch protein family has", "notch protein family has four", "protein family has four members:", "family has four members: notch1", "four members: notch1 notch2", "notch1 notch2 notch3", "notch2 notch3 and notch4.", "notch3 and notch4. notch1 protein", "and notch4. notch1 protein was", "notch4. notch1 protein was identified", "notch1 protein was identified first", "was identified first as", "identified first as the", "first as the product", "as the product of a", "the product of a chromosome", "product of a chromosome 9", "of a chromosome 9 gene", "a chromosome 9 gene translocated", "chromosome 9 gene translocated in", "9 gene translocated in t", "gene translocated in t cell", "translocated in t cell acute", "in t cell acute lymphoblastic", "t cell acute lymphoblastic leukemia", "cell acute lymphoblastic leukemia that", "acute lymphoblastic leukemia that was", "lymphoblastic leukemia that was homologous", "leukemia that was homologous to", "that was homologous to drosophila", "was homologous to drosophila notch", "to drosophila notch ellisen", "drosophila notch ellisen et", "notch ellisen et al.", "ellisen et al. 1991 .", "et al. 1991 . at", "al. 1991 . at the", "1991 . at the same", ". at the same time", "the same time rat", "same time rat notch1", "time rat notch1 was", "notch1 was cloned weinmaster", "was cloned weinmaster et", "cloned weinmaster et al.", "al. 1991 followed", "1991 followed by", "followed by cloning of mouse", "by cloning of mouse notch1", "of mouse notch1 named", "mouse notch1 named motch", "named motch del amo", "motch del amo et", "del amo et al. 1992", "amo et al. 1992 .", "et al. 1992 . notch2", "al. 1992 . notch2 protein", "1992 . notch2 protein is", ". notch2 protein is the", "notch2 protein is the product", "protein is the product of", "is the product of a", "the product of a gene", "product of a gene on", "of a gene on chromosome", "a gene on chromosome 1", "on chromosome 1 larsson", "chromosome 1 larsson et", "1 larsson et al.", "larsson et al. 1994 .", "et al. 1994 . notch2", "al. 1994 . notch2 expression", "1994 . notch2 expression is", ". notch2 expression is differentially", "notch2 expression is differentially regulated", "expression is differentially regulated during", "is differentially regulated during b", "differentially regulated during b cell", "regulated during b cell development", "b cell development bertrand", "cell development bertrand et", "development bertrand et al.", "bertrand et al. 2000 .", "et al. 2000 . notch2", "al. 2000 . notch2 mutations", "2000 . notch2 mutations are", ". notch2 mutations are a", "notch2 mutations are a rare", "mutations are a rare cause", "are a rare cause of", "a rare cause of alagille", "rare cause of alagille syndrome", "of alagille syndrome mcdaniell", "alagille syndrome mcdaniell et", "syndrome mcdaniell et al.", "mcdaniell et al. 2006 .", "et al. 2006 . notch3", "al. 2006 . notch3 is", "2006 . notch3 is the", ". notch3 is the product", "notch3 is the product of", "a gene on chromosome 19.", "gene on chromosome 19. notch3", "on chromosome 19. notch3 mutations", "chromosome 19. notch3 mutations are", "19. notch3 mutations are the", "notch3 mutations are the underlying", "mutations are the underlying cause", "are the underlying cause of", "the underlying cause of cadasil", "cause of cadasil cerebral", "of cadasil cerebral arteriopathy", "cadasil cerebral arteriopathy with", "cerebral arteriopathy with subcortical infarcts", "arteriopathy with subcortical infarcts and", "with subcortical infarcts and leukoencephalopathy", "infarcts and leukoencephalopathy joutel", "and leukoencephalopathy joutel et", "leukoencephalopathy joutel et al.", "joutel et al. 1996 .", "et al. 1996 . notch4", "1996 . notch4 the", ". notch4 the last", "notch4 the last notch", "the last notch protein discovered", "notch protein discovered is", "protein discovered is the", "discovered is the product", "a gene on chromosome 6", "on chromosome 6 li", "chromosome 6 li et", "6 li et al.", "li et al. 1998 .", "et al. 1998 .

micrornas", "al. 1998 .

micrornas play", "1998 .

micrornas play an", ".

micrornas play an important", "

micrornas play an important negative", "play an important negative role", "an important negative role in", "important negative role in translation", "negative role in translation and/or", "role in translation and/or stability", "in translation and/or stability of", "translation and/or stability of notch", "and/or stability of notch mrnas.", "stability of notch mrnas. micrornas", "of notch mrnas. micrornas mir", "notch mrnas. micrornas mir 34", "micrornas mir 34 mir", "mir 34 mir 34a", "mir 34a mir 34b", "34a mir 34b and", "mir 34b and mi r34c", "mi r34c whose", "r34c whose transcription", "whose transcription is directly induced", "transcription is directly induced by", "is directly induced by the", "directly induced by the tumor", "induced by the tumor suppressor", "by the tumor suppressor protein", "the tumor suppressor protein p53", "suppressor protein p53 chang", "protein p53 chang et", "p53 chang et al.", "et al. 2007 raver", "al. 2007 raver shapira", "2007 raver shapira et", "raver shapira et al. 2007", "et al. 2007 he", "al. 2007 he et", "2007 he et al.", "et al. 2007 corney", "al. 2007 corney et", "2007 corney et al.", "et al. 2007 bind", "al. 2007 bind and", "2007 bind and negatively", "bind and negatively regulate translation", "and negatively regulate translation of", "negatively regulate translation of notch1", "regulate translation of notch1 mrna", "of notch1 mrna li", "notch1 mrna li et", "mrna li et al.", "et al. 2009 pang", "al. 2009 pang et", "2009 pang et al.", "et al. 2010 ji", "al. 2010 ji et", "2010 ji et al.", "et al. 2009 and", "al. 2009 and notch2", "2009 and notch2 mrna", "and notch2 mrna li", "notch2 mrna li et", "li et al. 2009 .", "et al. 2009 . notch1", "al. 2009 . notch1 mrna", "2009 . notch1 mrna translation", ". notch1 mrna translation is", "notch1 mrna translation is also", "mrna translation is also negatively", "translation is also negatively regulated", "is also negatively regulated by", "also negatively regulated by micrornas", "negatively regulated by micrornas mir", "regulated by micrornas mir 200b", "by micrornas mir 200b and", "micrornas mir 200b and mir", "mir 200b and mir 200c", "and mir 200c kong", "mir 200c kong et", "200c kong et al.", "al. 2010 as", "2010 as well", "as well as mir 449a", "as mir 449a mir", "mir 449a mir 449b", "449a mir 449b and", "mir 449b and mir 449c", "and mir 449c marcet", "mir 449c marcet et", "449c marcet et al.", "marcet et al. 2011 .", "et al. 2011 . translation", "al. 2011 . translation of", "2011 . translation of notch3", ". translation of notch3 mrna", "translation of notch3 mrna is", "of notch3 mrna is negatively", "notch3 mrna is negatively regulated", "mrna is negatively regulated by", "is negatively regulated by micrornas", "regulated by micrornas mir 150", "micrornas mir 150 ghisi", "mir 150 ghisi et", "150 ghisi et al.", "et al. 2011 and", "al. 2011 and mir", "2011 and mir 206", "and mir 206 song", "mir 206 song et", "206 song et al.", "song et al. 2009 .", "et al. 2009 . translation", "al. 2009 . translation of", "2009 . translation of notch4", ". translation of notch4 mrna", "translation of notch4 mrna is", "of notch4 mrna is negatively", "notch4 mrna is negatively regulated", "regulated by micrornas mir 181c", "micrornas mir 181c hashimoto", "mir 181c hashimoto et", "181c hashimoto et al.", "et al. 2010 and", "al. 2010 and mir", "2010 and mir 302a", "and mir 302a costa", "mir 302a costa et", "302a costa et al.", "costa et al. 2009 .", "et al. 2009 .

the", "al. 2009 .

the notch2nl

", ".

the notch2nl

notch", "

the notch2nl

notch homolog", "notch2nl

notch homolog 2", "notch homolog 2 n terminal", "homolog 2 n terminal like", "n terminal like gene", "terminal like gene family", "like gene family includes", "gene family includes four genes", "includes four genes notch2nla", "genes notch2nla notch", "notch2nla notch homolog 2", "2 n terminal like a", "like a notch2nlb", "notch2nlb notch homolog 2", "2 n terminal like b", "like b notch2nlc", "notch2nlc notch homolog 2", "terminal like and", "like and notch2nlr", "and notch2nlr notch homolog", "notch2nlr notch homolog 2", "2 n terminal like r", "like r which", "r which originated", "which originated from the partial", "originated from the partial duplication", "from the partial duplication of", "the partial duplication of the", "partial duplication of the first", "duplication of the first four", "of the first four exons", "the first four exons and", "first four exons and introns", "four exons and introns of", "exons and introns of the", "and introns of the notch2", "introns of the notch2 gene", "of the notch2 gene and", "the notch2 gene and function", "notch2 gene and function to", "gene and function to modulate", "and function to modulate notch", "function to modulate notch signaling", "modulate notch signaling fiddes", "notch signaling fiddes et", "signaling fiddes et al.", "et al. 2018 florio", "al. 2018 florio et", "2018 florio et al.", "et al. 2018 suzuki", "al. 2018 suzuki et", "2018 suzuki et al.", "et al. 2018 lodewijk", "al. 2018 lodewijk et", "2018 lodewijk et al.", "lodewijk et al. 2020 .

nascent", "et al. 2020 .

nascent notch", "al. 2020 .

nascent notch peptides", "2020 .

nascent notch peptides are", ".

nascent notch peptides are co", "notch peptides are co translationally", "peptides are co translationally targeted", "are co translationally targeted to", "co translationally targeted to the", "translationally targeted to the endoplasmic", "targeted to the endoplasmic reticulum", "to the endoplasmic reticulum for", "the endoplasmic reticulum for further", "endoplasmic reticulum for further processing", "for further processing followed", "further processing followed by", "processing followed by modification", "followed by modification in the", "by modification in the golgi", "modification in the golgi apparatus", "the golgi apparatus before", "golgi apparatus before trafficking", "apparatus before trafficking to", "before trafficking to the plasma", "trafficking to the plasma membrane.", "to the plasma membrane. endoplasmic", "the plasma membrane. endoplasmic reticulum", "plasma membrane. endoplasmic reticulum calcium", "membrane. endoplasmic reticulum calcium atpases", "reticulum calcium atpases positively", "calcium atpases positively regulate", "atpases positively regulate notch", "regulate notch trafficking possibly", "notch trafficking possibly by", "trafficking possibly by contributing", "possibly by contributing to accurate", "by contributing to accurate folding", "contributing to accurate folding of", "to accurate folding of notch", "accurate folding of notch precursors", "of notch precursors periz", "notch precursors periz et", "precursors periz et al.", "periz et al. 1999 .

" ] }, { "record_id": "GLY_000594_1_155", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1912420", "r hsa", "hsa 1912420", "r hsa 1912420" ] }, { "record_id": "GLY_000594_1_155", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pre notch", "notch processing", "processing in", "in golgi", "pre notch processing", "notch processing in", "processing in golgi", "pre notch processing in", "notch processing in golgi", "pre notch processing in golgi", "notch undergoes", "undergoes final", "final posttranslational", "posttranslational processing", "in the", "the golgi", "golgi apparatus", "lardelli et", "et al.", "al. 1994", "blaumueller et", "al. 1997", "weinmaster et", "al. 1991", "al. 1992", "uyttendaele et", "al. 1996", "1996 .", ". movement", "movement of", "of notch", "notch precursors", "precursors from", "from the", "the endoplasmic", "endoplasmic reticulum", "reticulum to", "to golgi", "golgi is", "is controlled", "controlled by", "by sel1l", "sel1l protein", "a homolog", "homolog of", "of c.", "c. elegans", "elegans sel", "sel 1.", "1. sel1l", "sel1l localizes", "localizes to", "to the", "reticulum membrane", "membrane and", "and prevents", "prevents translocation", "translocation of", "of misfolded", "misfolded proteins", "therefore serving", "serving as", "as a", "a quality", "quality control", "control check", "li et", "al. 2010", "sundaram et", "al. 1993", "francisco et", "2010 .", ". similarly", "sel 9", "9 and", "and its", "its mammalian", "mammalian homolog", "homolog tmed2", "tmed2 are", "are golgi", "golgi membrane", "membrane proteins", "proteins that", "that participate", "participate in", "in quality", "control of", "of proteins", "proteins transported", "transported from", "from golgi", "golgi to", "the plasma", "plasma membrane.", "membrane. translocation", "of a", "a mutant", "mutant c.", "elegans notch", "notch homolog", "homolog lin", "lin 12", "12 from", "plasma membrane", "membrane is", "is negatively", "negatively regulated", "regulated by", "by sel", "wen et", "al. 1999", "1999 .", ". a", "a gtpase", "gtpase rab6", "rab6 positively", "positively controls", "controls notch", "notch trafficking", "trafficking through", "through golgi", "purcell et", ".

", "


processing", "
processing of", "of mammalian", "mammalian notch", "precursors in", "golgi typically", "typically involves", "involves the", "the cleavage", "cleavage by", "by furin", "furin convertase.", "convertase. pre", "notch is", "is a", "a ~300", "~300 kda", "kda protein", "and cleavage", "furin produces", "produces two", "two fragments", "fragments with", "with approximate", "approximate sizes", "sizes of", "of 110", "110 kda", "kda and", "and 180", "180 kda.", "kda. the", "the 110", "kda fragment", "fragment contains", "contains the", "the transmembrane", "transmembrane and", "and intracellular", "intracellular domains", "domains of", "notch and", "and is", "is known", "known as", "as ntm", "ntm or", "or ntmicd.", "ntmicd. the", "the 189", "189 kda", "contains notch", "notch extracellular", "extracellular sequence", "sequence and", "as nec", "nec or", "or necd.", "necd. the", "the ntm", "ntm and", "and nec", "nec fragments", "fragments heterodimerize", "logeat et", "al. 1998", "chan et", "and are", "are held", "held together", "together by", "by disulfide", "disulfide bonds", "bonds and", "and calcium", "calcium ions", "rand et", "al. 2000", "gordon et", "al. 2009", "2009 .", ".
", "

", "

an", "
an optional", "optional step", "step in", "in pre", "is modification", "modification by", "by fringe", "fringe enzymes.", "enzymes. fringe", "fringe enzymes", "enzymes are", "are glycosyl", "glycosyl transferases", "transferases that", "that initiate", "initiate elongation", "elongation of", "of o", "o linked", "linked fucose", "fucose on", "on fucosylated", "fucosylated peptides", "peptides by", "by addition", "addition of", "a beta", "beta 1", "1 3", "3 n", "n acetylglucosaminyl", "acetylglucosaminyl group", "resulting in", "in formation", "formation of", "of disaccharide", "disaccharide chains", "chains on", "on notch", "notch egf", "egf repeats", "glcnac bet1", "bet1 3", "3 fucitol", "fucitol .", ". three", "three fringe", "are known", "known in", "in mammals:", "mammals: lfng", "lunatic fringe", "manic fringe", "and rfng", "radical fringe", "fringe .", ". lfng", "lfng shows", "shows the", "the highest", "highest catalytic", "catalytic activity", "activity in", "in modifying", "modifying notch", "bruckner et", "moloney et", "2000 .", ". fringe", "fringe created", "created disaccharide", "repeats are", "are further", "further extended", "extended by", "by b4galt1", "1 4", "4 galactosyltransferase", "galactosyltransferase 1", "which adds", "adds galactose", "galactose to", "the n", "of trisaccharide", "trisaccharide gal", "gal beta1", "beta1 4", "4 glcnac", "glcnac beta1", "beta1 3", "fucitol chains", "chen et", "al. 2001", "2001 .", ". formation", "trisaccharide chains", "chains is", "is the", "the minimum", "minimum requirement", "requirement for", "for fringe", "fringe mediated", "mediated modulation", "modulation of", "notch signaling", "although fringe", "fringe modified", "modified notch", "notch expressed", "expressed on", "on the", "the cell", "cell surface", "surface predominantly", "predominantly contains", "contains tetrasaccharide", "tetrasaccharide chains", "on egf", "egf repeats.", "repeats. the", "the tetrasaccharide", "chains are", "are formed", "formed by", "by sialyltransferase", "sialyltransferase s", "that add", "add sialic", "sialic acid", "acid to", "to galactose", "of sia", "sia alpha2", "alpha2 3", "3 gal", "three known", "known golgi", "membrane sialyltransferases", "sialyltransferases could", "could be", "be performing", "performing this", "this function:", "function: st3gal3", "st3gal4 and", "and st3gal6", "harduin lepers", "lepers et", ". the", "the modification", "modification of", "notch by", "enzymes modulates", "modulates notch", "signaling by", "by increasing", "increasing the", "the affinity", "affinity of", "notch receptors", "receptors for", "for delta", "delta like", "like ligands", "dll1 and", "and dll4", "while decreasing", "decreasing affinity", "affinity for", "for jagged", "jagged ligands", "jag1 and", "and jag2.", "notch undergoes final", "undergoes final posttranslational", "final posttranslational processing", "posttranslational processing in", "processing in the", "in the golgi", "the golgi apparatus", "apparatus lardelli", "lardelli et al.", "et al. 1994", "1994 blaumueller", "blaumueller et al.", "et al. 1997", "1997 weinmaster", "weinmaster et al.", "et al. 1991", "1991 weinmaster", "et al. 1992", "1992 uyttendaele", "uyttendaele et al.", "et al. 1996", "al. 1996 .", "1996 . movement", ". movement of", "movement of notch", "of notch precursors", "notch precursors from", "precursors from the", "from the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum to", "reticulum to golgi", "to golgi is", "golgi is controlled", "is controlled by", "controlled by sel1l", "by sel1l protein", "protein a", "a homolog of", "homolog of c.", "of c. elegans", "c. elegans sel", "elegans sel 1.", "sel 1. sel1l", "1. sel1l localizes", "sel1l localizes to", "localizes to the", "to the endoplasmic", "endoplasmic reticulum membrane", "reticulum membrane and", "membrane and prevents", "and prevents translocation", "prevents translocation of", "translocation of misfolded", "of misfolded proteins", "proteins therefore", "therefore serving as", "serving as a", "as a quality", "a quality control", "quality control check", "check li", "li et al.", "et al. 2010", "2010 sundaram", "sundaram et al.", "et al. 1993", "1993 francisco", "francisco et al.", "al. 2010 .", "2010 . similarly", "similarly c.", "elegans sel 9", "sel 9 and", "9 and its", "and its mammalian", "its mammalian homolog", "mammalian homolog tmed2", "homolog tmed2 are", "tmed2 are golgi", "are golgi membrane", "golgi membrane proteins", "membrane proteins that", "proteins that participate", "that participate in", "participate in quality", "in quality control", "quality control of", "control of proteins", "of proteins transported", "proteins transported from", "transported from golgi", "from golgi to", "golgi to the", "to the plasma", "the plasma membrane.", "plasma membrane. translocation", "membrane. translocation of", "translocation of a", "of a mutant", "a mutant c.", "mutant c. elegans", "c. elegans notch", "elegans notch homolog", "notch homolog lin", "homolog lin 12", "lin 12 from", "12 from the", "from the golgi", "the golgi to", "the plasma membrane", "plasma membrane is", "membrane is negatively", "is negatively regulated", "negatively regulated by", "regulated by sel", "by sel 9", "9 wen", "wen et al.", "et al. 1999", "al. 1999 .", "1999 . a", ". a gtpase", "a gtpase rab6", "gtpase rab6 positively", "rab6 positively controls", "positively controls notch", "controls notch trafficking", "notch trafficking through", "trafficking through golgi", "golgi purcell", "purcell et al.", "1999 .

", ".


processing", "


processing of", "
processing of mammalian", "of mammalian notch", "mammalian notch precursors", "notch precursors in", "precursors in the", "the golgi typically", "golgi typically involves", "typically involves the", "involves the cleavage", "the cleavage by", "cleavage by furin", "by furin convertase.", "furin convertase. pre", "convertase. pre notch", "pre notch is", "notch is a", "is a ~300", "a ~300 kda", "~300 kda protein", "protein and", "and cleavage by", "by furin produces", "furin produces two", "produces two fragments", "two fragments with", "fragments with approximate", "with approximate sizes", "approximate sizes of", "sizes of 110", "of 110 kda", "110 kda and", "kda and 180", "and 180 kda.", "180 kda. the", "kda. the 110", "the 110 kda", "110 kda fragment", "kda fragment contains", "fragment contains the", "contains the transmembrane", "the transmembrane and", "transmembrane and intracellular", "and intracellular domains", "intracellular domains of", "domains of notch", "of notch and", "notch and is", "and is known", "is known as", "known as ntm", "as ntm or", "ntm or ntmicd.", "or ntmicd. the", "ntmicd. the 189", "the 189 kda", "189 kda fragment", "fragment contains notch", "contains notch extracellular", "notch extracellular sequence", "extracellular sequence and", "sequence and is", "known as nec", "as nec or", "nec or necd.", "or necd. the", "necd. the ntm", "the ntm and", "ntm and nec", "and nec fragments", "nec fragments heterodimerize", "heterodimerize blaumueller", "1997 logeat", "logeat et al.", "et al. 1998", "1998 chan", "chan et al.", "1998 and", "and are held", "are held together", "held together by", "together by disulfide", "by disulfide bonds", "disulfide bonds and", "bonds and calcium", "and calcium ions", "ions rand", "rand et al.", "et al. 2000", "2000 gordon", "gordon et al.", "et al. 2009", "al. 2009 .", "2009 .
", ".

", "


an", "

an optional", "
an optional step", "optional step in", "step in pre", "in pre notch", "the golgi is", "golgi is modification", "is modification by", "modification by fringe", "by fringe enzymes.", "fringe enzymes. fringe", "enzymes. fringe enzymes", "fringe enzymes are", "enzymes are glycosyl", "are glycosyl transferases", "glycosyl transferases that", "transferases that initiate", "that initiate elongation", "initiate elongation of", "elongation of o", "of o linked", "o linked fucose", "linked fucose on", "fucose on fucosylated", "on fucosylated peptides", "fucosylated peptides by", "peptides by addition", "by addition of", "addition of a", "of a beta", "a beta 1", "beta 1 3", "1 3 n", "3 n acetylglucosaminyl", "n acetylglucosaminyl group", "group resulting", "resulting in formation", "in formation of", "formation of disaccharide", "of disaccharide chains", "disaccharide chains on", "chains on notch", "on notch egf", "notch egf repeats", "repeats glcnac", "glcnac bet1 3", "bet1 3 fucitol", "3 fucitol .", "fucitol . three", ". three fringe", "three fringe enzymes", "enzymes are known", "are known in", "known in mammals:", "in mammals: lfng", "lfng lunatic", "mfng manic", "fringe and", "rfng radical", "radical fringe .", "fringe . lfng", ". lfng shows", "lfng shows the", "shows the highest", "the highest catalytic", "highest catalytic activity", "catalytic activity in", "activity in modifying", "in modifying notch", "notch bruckner", "bruckner et al.", "2000 moloney", "moloney et al.", "al. 2000 .", "2000 . fringe", ". fringe created", "fringe created disaccharide", "created disaccharide chains", "egf repeats are", "repeats are further", "are further extended", "further extended by", "extended by b4galt1", "b4galt1 beta", "beta 1 4", "1 4 galactosyltransferase", "4 galactosyltransferase 1", "which adds galactose", "adds galactose to", "galactose to the", "to the n", "the n acetylglucosaminyl", "formation of trisaccharide", "of trisaccharide gal", "trisaccharide gal beta1", "gal beta1 4", "beta1 4 glcnac", "4 glcnac beta1", "glcnac beta1 3", "beta1 3 fucitol", "3 fucitol chains", "chains moloney", "2000 chen", "chen et al.", "et al. 2001", "al. 2001 .", "2001 . formation", ". formation of", "of trisaccharide chains", "trisaccharide chains is", "chains is the", "is the minimum", "the minimum requirement", "minimum requirement for", "requirement for fringe", "for fringe mediated", "fringe mediated modulation", "mediated modulation of", "modulation of notch", "of notch signaling", "signaling although", "although fringe modified", "fringe modified notch", "modified notch expressed", "notch expressed on", "expressed on the", "on the cell", "the cell surface", "cell surface predominantly", "surface predominantly contains", "predominantly contains tetrasaccharide", "contains tetrasaccharide chains", "tetrasaccharide chains on", "chains on egf", "on egf repeats.", "egf repeats. the", "repeats. the tetrasaccharide", "the tetrasaccharide chains", "tetrasaccharide chains are", "chains are formed", "are formed by", "formed by sialyltransferase", "by sialyltransferase s", "s that", "that add sialic", "add sialic acid", "sialic acid to", "acid to galactose", "galactose resulting", "formation of sia", "of sia alpha2", "sia alpha2 3", "alpha2 3 gal", "3 gal beta1", "fucitol moloney", "2000 . three", ". three known", "three known golgi", "known golgi membrane", "golgi membrane sialyltransferases", "membrane sialyltransferases could", "sialyltransferases could be", "could be performing", "be performing this", "performing this function:", "this function: st3gal3", "st3gal3 st3gal4", "st3gal4 and st3gal6", "st3gal6 harduin", "harduin lepers et", "lepers et al.", "2001 . the", ". the modification", "the modification of", "modification of notch", "of notch by", "notch by fringe", "by fringe enzymes", "fringe enzymes modulates", "enzymes modulates notch", "modulates notch signaling", "notch signaling by", "signaling by increasing", "by increasing the", "increasing the affinity", "the affinity of", "affinity of notch", "of notch receptors", "notch receptors for", "receptors for delta", "for delta like", "delta like ligands", "ligands dll1", "dll1 and dll4", "dll4 while", "while decreasing affinity", "decreasing affinity for", "affinity for jagged", "for jagged ligands", "ligands jag1", "jag1 and jag2.", "notch undergoes final posttranslational", "undergoes final posttranslational processing", "final posttranslational processing in", "posttranslational processing in the", "processing in the golgi", "in the golgi apparatus", "golgi apparatus lardelli", "apparatus lardelli et", "lardelli et al. 1994", "al. 1994 blaumueller", "1994 blaumueller et", "blaumueller et al. 1997", "al. 1997 weinmaster", "1997 weinmaster et", "weinmaster et al. 1991", "al. 1991 weinmaster", "1991 weinmaster et", "weinmaster et al. 1992", "al. 1992 uyttendaele", "1992 uyttendaele et", "uyttendaele et al. 1996", "et al. 1996 .", "al. 1996 . movement", "1996 . movement of", ". movement of notch", "movement of notch precursors", "of notch precursors from", "notch precursors from the", "precursors from the endoplasmic", "from the endoplasmic reticulum", "the endoplasmic reticulum to", "endoplasmic reticulum to golgi", "reticulum to golgi is", "to golgi is controlled", "golgi is controlled by", "is controlled by sel1l", "controlled by sel1l protein", "sel1l protein a", "protein a homolog", "a homolog of c.", "homolog of c. elegans", "of c. elegans sel", "c. elegans sel 1.", "elegans sel 1. sel1l", "sel 1. sel1l localizes", "1. sel1l localizes to", "sel1l localizes to the", "localizes to the endoplasmic", "to the endoplasmic reticulum", "the endoplasmic reticulum membrane", "endoplasmic reticulum membrane and", "reticulum membrane and prevents", "membrane and prevents translocation", "and prevents translocation of", "prevents translocation of misfolded", "translocation of misfolded proteins", "misfolded proteins therefore", "proteins therefore serving", "therefore serving as a", "serving as a quality", "as a quality control", "a quality control check", "control check li", "check li et", "li et al. 2010", "al. 2010 sundaram", "2010 sundaram et", "sundaram et al. 1993", "al. 1993 francisco", "1993 francisco et", "francisco et al. 2010", "et al. 2010 .", "al. 2010 . similarly", ". similarly c.", "similarly c. elegans", "c. elegans sel 9", "elegans sel 9 and", "sel 9 and its", "9 and its mammalian", "and its mammalian homolog", "its mammalian homolog tmed2", "mammalian homolog tmed2 are", "homolog tmed2 are golgi", "tmed2 are golgi membrane", "are golgi membrane proteins", "golgi membrane proteins that", "membrane proteins that participate", "proteins that participate in", "that participate in quality", "participate in quality control", "in quality control of", "quality control of proteins", "control of proteins transported", "of proteins transported from", "proteins transported from golgi", "transported from golgi to", "from golgi to the", "golgi to the plasma", "to the plasma membrane.", "the plasma membrane. translocation", "plasma membrane. translocation of", "membrane. translocation of a", "translocation of a mutant", "of a mutant c.", "a mutant c. elegans", "mutant c. elegans notch", "c. elegans notch homolog", "elegans notch homolog lin", "notch homolog lin 12", "homolog lin 12 from", "lin 12 from the", "12 from the golgi", "from the golgi to", "the golgi to the", "to the plasma membrane", "the plasma membrane is", "plasma membrane is negatively", "membrane is negatively regulated", "is negatively regulated by", "negatively regulated by sel", "regulated by sel 9", "sel 9 wen", "9 wen et", "wen et al. 1999", "et al. 1999 .", "al. 1999 . a", "1999 . a gtpase", ". a gtpase rab6", "a gtpase rab6 positively", "gtpase rab6 positively controls", "rab6 positively controls notch", "positively controls notch trafficking", "controls notch trafficking through", "notch trafficking through golgi", "through golgi purcell", "golgi purcell et", "purcell et al. 1999", "al. 1999 .

", "1999 .


processing", ".


processing of", "


processing of mammalian", "
processing of mammalian notch", "of mammalian notch precursors", "mammalian notch precursors in", "notch precursors in the", "precursors in the golgi", "in the golgi typically", "the golgi typically involves", "golgi typically involves the", "typically involves the cleavage", "involves the cleavage by", "the cleavage by furin", "cleavage by furin convertase.", "by furin convertase. pre", "furin convertase. pre notch", "convertase. pre notch is", "pre notch is a", "notch is a ~300", "is a ~300 kda", "a ~300 kda protein", "kda protein and", "protein and cleavage", "and cleavage by furin", "cleavage by furin produces", "by furin produces two", "furin produces two fragments", "produces two fragments with", "two fragments with approximate", "fragments with approximate sizes", "with approximate sizes of", "approximate sizes of 110", "sizes of 110 kda", "of 110 kda and", "110 kda and 180", "kda and 180 kda.", "and 180 kda. the", "180 kda. the 110", "kda. the 110 kda", "the 110 kda fragment", "110 kda fragment contains", "kda fragment contains the", "fragment contains the transmembrane", "contains the transmembrane and", "the transmembrane and intracellular", "transmembrane and intracellular domains", "and intracellular domains of", "intracellular domains of notch", "domains of notch and", "of notch and is", "notch and is known", "and is known as", "is known as ntm", "known as ntm or", "as ntm or ntmicd.", "ntm or ntmicd. the", "or ntmicd. the 189", "ntmicd. the 189 kda", "the 189 kda fragment", "189 kda fragment contains", "kda fragment contains notch", "fragment contains notch extracellular", "contains notch extracellular sequence", "notch extracellular sequence and", "extracellular sequence and is", "sequence and is known", "is known as nec", "known as nec or", "as nec or necd.", "nec or necd. the", "or necd. the ntm", "necd. the ntm and", "the ntm and nec", "ntm and nec fragments", "and nec fragments heterodimerize", "fragments heterodimerize blaumueller", "heterodimerize blaumueller et", "al. 1997 logeat", "1997 logeat et", "logeat et al. 1998", "al. 1998 chan", "1998 chan et", "chan et al. 1998", "al. 1998 and", "1998 and are", "and are held together", "are held together by", "held together by disulfide", "together by disulfide bonds", "by disulfide bonds and", "disulfide bonds and calcium", "bonds and calcium ions", "calcium ions rand", "ions rand et", "rand et al. 2000", "al. 2000 gordon", "2000 gordon et", "gordon et al. 2009", "et al. 2009 .", "al. 2009 .
", "2009 .

", ".


an", "


an optional", "

an optional step", "
an optional step in", "optional step in pre", "step in pre notch", "in pre notch processing", "notch processing in the", "in the golgi is", "the golgi is modification", "golgi is modification by", "is modification by fringe", "modification by fringe enzymes.", "by fringe enzymes. fringe", "fringe enzymes. fringe enzymes", "enzymes. fringe enzymes are", "fringe enzymes are glycosyl", "enzymes are glycosyl transferases", "are glycosyl transferases that", "glycosyl transferases that initiate", "transferases that initiate elongation", "that initiate elongation of", "initiate elongation of o", "elongation of o linked", "of o linked fucose", "o linked fucose on", "linked fucose on fucosylated", "fucose on fucosylated peptides", "on fucosylated peptides by", "fucosylated peptides by addition", "peptides by addition of", "by addition of a", "addition of a beta", "of a beta 1", "a beta 1 3", "beta 1 3 n", "1 3 n acetylglucosaminyl", "3 n acetylglucosaminyl group", "acetylglucosaminyl group resulting", "group resulting in", "resulting in formation of", "in formation of disaccharide", "formation of disaccharide chains", "of disaccharide chains on", "disaccharide chains on notch", "chains on notch egf", "on notch egf repeats", "egf repeats glcnac", "repeats glcnac bet1", "glcnac bet1 3 fucitol", "bet1 3 fucitol .", "3 fucitol . three", "fucitol . three fringe", ". three fringe enzymes", "three fringe enzymes are", "fringe enzymes are known", "enzymes are known in", "are known in mammals:", "known in mammals: lfng", "mammals: lfng lunatic", "lfng lunatic fringe", "fringe mfng", "mfng manic fringe", "manic fringe and", "fringe and rfng", "and rfng radical", "rfng radical fringe", "radical fringe . lfng", "fringe . lfng shows", ". lfng shows the", "lfng shows the highest", "shows the highest catalytic", "the highest catalytic activity", "highest catalytic activity in", "catalytic activity in modifying", "activity in modifying notch", "modifying notch bruckner", "notch bruckner et", "bruckner et al. 2000", "al. 2000 moloney", "2000 moloney et", "moloney et al. 2000", "et al. 2000 .", "al. 2000 . fringe", "2000 . fringe created", ". fringe created disaccharide", "fringe created disaccharide chains", "created disaccharide chains on", "notch egf repeats are", "egf repeats are further", "repeats are further extended", "are further extended by", "further extended by b4galt1", "by b4galt1 beta", "b4galt1 beta 1", "beta 1 4 galactosyltransferase", "1 4 galactosyltransferase 1", "1 which", "which adds galactose to", "adds galactose to the", "galactose to the n", "to the n acetylglucosaminyl", "the n acetylglucosaminyl group", "in formation of trisaccharide", "formation of trisaccharide gal", "of trisaccharide gal beta1", "trisaccharide gal beta1 4", "gal beta1 4 glcnac", "beta1 4 glcnac beta1", "4 glcnac beta1 3", "glcnac beta1 3 fucitol", "beta1 3 fucitol chains", "fucitol chains moloney", "chains moloney et", "al. 2000 chen", "2000 chen et", "chen et al. 2001", "et al. 2001 .", "al. 2001 . formation", "2001 . formation of", ". formation of trisaccharide", "formation of trisaccharide chains", "of trisaccharide chains is", "trisaccharide chains is the", "chains is the minimum", "is the minimum requirement", "the minimum requirement for", "minimum requirement for fringe", "requirement for fringe mediated", "for fringe mediated modulation", "fringe mediated modulation of", "mediated modulation of notch", "modulation of notch signaling", "notch signaling although", "signaling although fringe", "although fringe modified notch", "fringe modified notch expressed", "modified notch expressed on", "notch expressed on the", "expressed on the cell", "on the cell surface", "the cell surface predominantly", "cell surface predominantly contains", "surface predominantly contains tetrasaccharide", "predominantly contains tetrasaccharide chains", "contains tetrasaccharide chains on", "tetrasaccharide chains on egf", "chains on egf repeats.", "on egf repeats. the", "egf repeats. the tetrasaccharide", "repeats. the tetrasaccharide chains", "the tetrasaccharide chains are", "tetrasaccharide chains are formed", "chains are formed by", "are formed by sialyltransferase", "formed by sialyltransferase s", "sialyltransferase s that", "s that add", "that add sialic acid", "add sialic acid to", "sialic acid to galactose", "to galactose resulting", "galactose resulting in", "in formation of sia", "formation of sia alpha2", "of sia alpha2 3", "sia alpha2 3 gal", "alpha2 3 gal beta1", "3 gal beta1 4", "3 fucitol moloney", "fucitol moloney et", "al. 2000 . three", "2000 . three known", ". three known golgi", "three known golgi membrane", "known golgi membrane sialyltransferases", "golgi membrane sialyltransferases could", "membrane sialyltransferases could be", "sialyltransferases could be performing", "could be performing this", "be performing this function:", "performing this function: st3gal3", "function: st3gal3 st3gal4", "st3gal3 st3gal4 and", "and st3gal6 harduin", "st3gal6 harduin lepers", "harduin lepers et al.", "lepers et al. 2001", "al. 2001 . the", "2001 . the modification", ". the modification of", "the modification of notch", "modification of notch by", "of notch by fringe", "notch by fringe enzymes", "by fringe enzymes modulates", "fringe enzymes modulates notch", "enzymes modulates notch signaling", "modulates notch signaling by", "notch signaling by increasing", "signaling by increasing the", "by increasing the affinity", "increasing the affinity of", "the affinity of notch", "affinity of notch receptors", "of notch receptors for", "notch receptors for delta", "receptors for delta like", "for delta like ligands", "like ligands dll1", "ligands dll1 and", "and dll4 while", "dll4 while decreasing", "while decreasing affinity for", "decreasing affinity for jagged", "affinity for jagged ligands", "jagged ligands jag1", "ligands jag1 and", "notch undergoes final posttranslational processing", "undergoes final posttranslational processing in", "final posttranslational processing in the", "posttranslational processing in the golgi", "processing in the golgi apparatus", "the golgi apparatus lardelli", "golgi apparatus lardelli et", "apparatus lardelli et al.", "et al. 1994 blaumueller", "al. 1994 blaumueller et", "1994 blaumueller et al.", "et al. 1997 weinmaster", "al. 1997 weinmaster et", "1997 weinmaster et al.", "et al. 1991 weinmaster", "al. 1991 weinmaster et", "1991 weinmaster et al.", "et al. 1992 uyttendaele", "al. 1992 uyttendaele et", "1992 uyttendaele et al.", "uyttendaele et al. 1996 .", "et al. 1996 . movement", "al. 1996 . movement of", "1996 . movement of notch", ". movement of notch precursors", "movement of notch precursors from", "of notch precursors from the", "notch precursors from the endoplasmic", "precursors from the endoplasmic reticulum", "from the endoplasmic reticulum to", "the endoplasmic reticulum to golgi", "endoplasmic reticulum to golgi is", "reticulum to golgi is controlled", "to golgi is controlled by", "golgi is controlled by sel1l", "is controlled by sel1l protein", "by sel1l protein a", "sel1l protein a homolog", "protein a homolog of", "a homolog of c. elegans", "homolog of c. elegans sel", "of c. elegans sel 1.", "c. elegans sel 1. sel1l", "elegans sel 1. sel1l localizes", "sel 1. sel1l localizes to", "1. sel1l localizes to the", "sel1l localizes to the endoplasmic", "localizes to the endoplasmic reticulum", "to the endoplasmic reticulum membrane", "the endoplasmic reticulum membrane and", "endoplasmic reticulum membrane and prevents", "reticulum membrane and prevents translocation", "membrane and prevents translocation of", "and prevents translocation of misfolded", "prevents translocation of misfolded proteins", "of misfolded proteins therefore", "misfolded proteins therefore serving", "proteins therefore serving as", "therefore serving as a quality", "serving as a quality control", "as a quality control check", "quality control check li", "control check li et", "check li et al.", "et al. 2010 sundaram", "al. 2010 sundaram et", "2010 sundaram et al.", "et al. 1993 francisco", "al. 1993 francisco et", "1993 francisco et al.", "francisco et al. 2010 .", "et al. 2010 . similarly", "2010 . similarly c.", ". similarly c. elegans", "similarly c. elegans sel", "c. elegans sel 9 and", "elegans sel 9 and its", "sel 9 and its mammalian", "9 and its mammalian homolog", "and its mammalian homolog tmed2", "its mammalian homolog tmed2 are", "mammalian homolog tmed2 are golgi", "homolog tmed2 are golgi membrane", "tmed2 are golgi membrane proteins", "are golgi membrane proteins that", "golgi membrane proteins that participate", "membrane proteins that participate in", "proteins that participate in quality", "that participate in quality control", "participate in quality control of", "in quality control of proteins", "quality control of proteins transported", "control of proteins transported from", "of proteins transported from golgi", "proteins transported from golgi to", "transported from golgi to the", "from golgi to the plasma", "golgi to the plasma membrane.", "to the plasma membrane. translocation", "the plasma membrane. translocation of", "plasma membrane. translocation of a", "membrane. translocation of a mutant", "translocation of a mutant c.", "of a mutant c. elegans", "a mutant c. elegans notch", "mutant c. elegans notch homolog", "c. elegans notch homolog lin", "elegans notch homolog lin 12", "notch homolog lin 12 from", "homolog lin 12 from the", "lin 12 from the golgi", "12 from the golgi to", "from the golgi to the", "the golgi to the plasma", "golgi to the plasma membrane", "to the plasma membrane is", "the plasma membrane is negatively", "plasma membrane is negatively regulated", "membrane is negatively regulated by", "is negatively regulated by sel", "negatively regulated by sel 9", "by sel 9 wen", "sel 9 wen et", "9 wen et al.", "wen et al. 1999 .", "et al. 1999 . a", "al. 1999 . a gtpase", "1999 . a gtpase rab6", ". a gtpase rab6 positively", "a gtpase rab6 positively controls", "gtpase rab6 positively controls notch", "rab6 positively controls notch trafficking", "positively controls notch trafficking through", "controls notch trafficking through golgi", "trafficking through golgi purcell", "through golgi purcell et", "golgi purcell et al.", "purcell et al. 1999 .", "et al. 1999 .

", "al. 1999 .


processing", "1999 .


processing of", ".


processing of mammalian", "


processing of mammalian notch", "
processing of mammalian notch precursors", "of mammalian notch precursors in", "mammalian notch precursors in the", "notch precursors in the golgi", "precursors in the golgi typically", "in the golgi typically involves", "the golgi typically involves the", "golgi typically involves the cleavage", "typically involves the cleavage by", "involves the cleavage by furin", "the cleavage by furin convertase.", "cleavage by furin convertase. pre", "by furin convertase. pre notch", "furin convertase. pre notch is", "convertase. pre notch is a", "pre notch is a ~300", "notch is a ~300 kda", "is a ~300 kda protein", "~300 kda protein and", "kda protein and cleavage", "protein and cleavage by", "and cleavage by furin produces", "cleavage by furin produces two", "by furin produces two fragments", "furin produces two fragments with", "produces two fragments with approximate", "two fragments with approximate sizes", "fragments with approximate sizes of", "with approximate sizes of 110", "approximate sizes of 110 kda", "sizes of 110 kda and", "of 110 kda and 180", "110 kda and 180 kda.", "kda and 180 kda. the", "and 180 kda. the 110", "180 kda. the 110 kda", "kda. the 110 kda fragment", "the 110 kda fragment contains", "110 kda fragment contains the", "kda fragment contains the transmembrane", "fragment contains the transmembrane and", "contains the transmembrane and intracellular", "the transmembrane and intracellular domains", "transmembrane and intracellular domains of", "and intracellular domains of notch", "intracellular domains of notch and", "domains of notch and is", "of notch and is known", "notch and is known as", "and is known as ntm", "is known as ntm or", "known as ntm or ntmicd.", "as ntm or ntmicd. the", "ntm or ntmicd. the 189", "or ntmicd. the 189 kda", "ntmicd. the 189 kda fragment", "the 189 kda fragment contains", "189 kda fragment contains notch", "kda fragment contains notch extracellular", "fragment contains notch extracellular sequence", "contains notch extracellular sequence and", "notch extracellular sequence and is", "extracellular sequence and is known", "sequence and is known as", "and is known as nec", "is known as nec or", "known as nec or necd.", "as nec or necd. the", "nec or necd. the ntm", "or necd. the ntm and", "necd. the ntm and nec", "the ntm and nec fragments", "ntm and nec fragments heterodimerize", "nec fragments heterodimerize blaumueller", "fragments heterodimerize blaumueller et", "heterodimerize blaumueller et al.", "et al. 1997 logeat", "al. 1997 logeat et", "1997 logeat et al.", "et al. 1998 chan", "al. 1998 chan et", "1998 chan et al.", "et al. 1998 and", "al. 1998 and are", "1998 and are held", "and are held together by", "are held together by disulfide", "held together by disulfide bonds", "together by disulfide bonds and", "by disulfide bonds and calcium", "disulfide bonds and calcium ions", "and calcium ions rand", "calcium ions rand et", "ions rand et al.", "et al. 2000 gordon", "al. 2000 gordon et", "2000 gordon et al.", "gordon et al. 2009 .", "et al. 2009 .
", "al. 2009 .

", "2009 .


an", ".


an optional", "


an optional step", "

an optional step in", "
an optional step in pre", "optional step in pre notch", "step in pre notch processing", "in pre notch processing in", "pre notch processing in the", "notch processing in the golgi", "processing in the golgi is", "in the golgi is modification", "the golgi is modification by", "golgi is modification by fringe", "is modification by fringe enzymes.", "modification by fringe enzymes. fringe", "by fringe enzymes. fringe enzymes", "fringe enzymes. fringe enzymes are", "enzymes. fringe enzymes are glycosyl", "fringe enzymes are glycosyl transferases", "enzymes are glycosyl transferases that", "are glycosyl transferases that initiate", "glycosyl transferases that initiate elongation", "transferases that initiate elongation of", "that initiate elongation of o", "initiate elongation of o linked", "elongation of o linked fucose", "of o linked fucose on", "o linked fucose on fucosylated", "linked fucose on fucosylated peptides", "fucose on fucosylated peptides by", "on fucosylated peptides by addition", "fucosylated peptides by addition of", "peptides by addition of a", "by addition of a beta", "addition of a beta 1", "of a beta 1 3", "a beta 1 3 n", "beta 1 3 n acetylglucosaminyl", "1 3 n acetylglucosaminyl group", "n acetylglucosaminyl group resulting", "acetylglucosaminyl group resulting in", "group resulting in formation", "resulting in formation of disaccharide", "in formation of disaccharide chains", "formation of disaccharide chains on", "of disaccharide chains on notch", "disaccharide chains on notch egf", "chains on notch egf repeats", "notch egf repeats glcnac", "egf repeats glcnac bet1", "repeats glcnac bet1 3", "glcnac bet1 3 fucitol .", "bet1 3 fucitol . three", "3 fucitol . three fringe", "fucitol . three fringe enzymes", ". three fringe enzymes are", "three fringe enzymes are known", "fringe enzymes are known in", "enzymes are known in mammals:", "are known in mammals: lfng", "in mammals: lfng lunatic", "mammals: lfng lunatic fringe", "lunatic fringe mfng", "manic fringe and rfng", "and rfng radical fringe", "rfng radical fringe .", "radical fringe . lfng shows", "fringe . lfng shows the", ". lfng shows the highest", "lfng shows the highest catalytic", "shows the highest catalytic activity", "the highest catalytic activity in", "highest catalytic activity in modifying", "catalytic activity in modifying notch", "in modifying notch bruckner", "modifying notch bruckner et", "notch bruckner et al.", "et al. 2000 moloney", "al. 2000 moloney et", "2000 moloney et al.", "moloney et al. 2000 .", "et al. 2000 . fringe", "al. 2000 . fringe created", "2000 . fringe created disaccharide", ". fringe created disaccharide chains", "fringe created disaccharide chains on", "created disaccharide chains on notch", "on notch egf repeats are", "notch egf repeats are further", "egf repeats are further extended", "repeats are further extended by", "are further extended by b4galt1", "extended by b4galt1 beta", "by b4galt1 beta 1", "b4galt1 beta 1 4", "beta 1 4 galactosyltransferase 1", "galactosyltransferase 1 which", "1 which adds", "which adds galactose to the", "adds galactose to the n", "galactose to the n acetylglucosaminyl", "to the n acetylglucosaminyl group", "resulting in formation of trisaccharide", "in formation of trisaccharide gal", "formation of trisaccharide gal beta1", "of trisaccharide gal beta1 4", "trisaccharide gal beta1 4 glcnac", "gal beta1 4 glcnac beta1", "beta1 4 glcnac beta1 3", "4 glcnac beta1 3 fucitol", "glcnac beta1 3 fucitol chains", "3 fucitol chains moloney", "fucitol chains moloney et", "chains moloney et al.", "et al. 2000 chen", "al. 2000 chen et", "2000 chen et al.", "chen et al. 2001 .", "et al. 2001 . formation", "al. 2001 . formation of", "2001 . formation of trisaccharide", ". formation of trisaccharide chains", "formation of trisaccharide chains is", "of trisaccharide chains is the", "trisaccharide chains is the minimum", "chains is the minimum requirement", "is the minimum requirement for", "the minimum requirement for fringe", "minimum requirement for fringe mediated", "requirement for fringe mediated modulation", "for fringe mediated modulation of", "fringe mediated modulation of notch", "mediated modulation of notch signaling", "of notch signaling although", "notch signaling although fringe", "signaling although fringe modified", "although fringe modified notch expressed", "fringe modified notch expressed on", "modified notch expressed on the", "notch expressed on the cell", "expressed on the cell surface", "on the cell surface predominantly", "the cell surface predominantly contains", "cell surface predominantly contains tetrasaccharide", "surface predominantly contains tetrasaccharide chains", "predominantly contains tetrasaccharide chains on", "contains tetrasaccharide chains on egf", "tetrasaccharide chains on egf repeats.", "chains on egf repeats. the", "on egf repeats. the tetrasaccharide", "egf repeats. the tetrasaccharide chains", "repeats. the tetrasaccharide chains are", "the tetrasaccharide chains are formed", "tetrasaccharide chains are formed by", "chains are formed by sialyltransferase", "are formed by sialyltransferase s", "by sialyltransferase s that", "sialyltransferase s that add", "s that add sialic", "that add sialic acid to", "add sialic acid to galactose", "acid to galactose resulting", "to galactose resulting in", "galactose resulting in formation", "resulting in formation of sia", "in formation of sia alpha2", "formation of sia alpha2 3", "of sia alpha2 3 gal", "sia alpha2 3 gal beta1", "alpha2 3 gal beta1 4", "3 gal beta1 4 glcnac", "beta1 3 fucitol moloney", "3 fucitol moloney et", "fucitol moloney et al.", "et al. 2000 . three", "al. 2000 . three known", "2000 . three known golgi", ". three known golgi membrane", "three known golgi membrane sialyltransferases", "known golgi membrane sialyltransferases could", "golgi membrane sialyltransferases could be", "membrane sialyltransferases could be performing", "sialyltransferases could be performing this", "could be performing this function:", "be performing this function: st3gal3", "this function: st3gal3 st3gal4", "function: st3gal3 st3gal4 and", "st3gal3 st3gal4 and st3gal6", "st3gal4 and st3gal6 harduin", "and st3gal6 harduin lepers", "st3gal6 harduin lepers et", "harduin lepers et al. 2001", "lepers et al. 2001 .", "et al. 2001 . the", "al. 2001 . the modification", "2001 . the modification of", ". the modification of notch", "the modification of notch by", "modification of notch by fringe", "of notch by fringe enzymes", "notch by fringe enzymes modulates", "by fringe enzymes modulates notch", "fringe enzymes modulates notch signaling", "enzymes modulates notch signaling by", "modulates notch signaling by increasing", "notch signaling by increasing the", "signaling by increasing the affinity", "by increasing the affinity of", "increasing the affinity of notch", "the affinity of notch receptors", "affinity of notch receptors for", "of notch receptors for delta", "notch receptors for delta like", "receptors for delta like ligands", "delta like ligands dll1", "like ligands dll1 and", "ligands dll1 and dll4", "dll1 and dll4 while", "and dll4 while decreasing", "dll4 while decreasing affinity", "while decreasing affinity for jagged", "decreasing affinity for jagged ligands", "for jagged ligands jag1", "jagged ligands jag1 and", "ligands jag1 and jag2." ] }, { "record_id": "GLY_000594_1_156", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "191859", "r hsa", "hsa 191859", "r hsa 191859" ] }, { "record_id": "GLY_000594_1_156", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "snrnp assembly", "small nuclear", "nuclear ribonucleoproteins", "are crucial", "crucial for", "for pre", "pre mrna", "mrna processing", "processing to", "to mrnas.", "mrnas. each", "each snrnp", "snrnp contains", "contains a", "a small", "nuclear rna", "and an", "an extremely", "extremely stable", "stable core", "core of", "of seven", "seven sm", "sm proteins.", "proteins. the", "the u6", "u6 snrna", "snrna differs", "differs from", "from the", "the other", "other snrnas", "it binds", "binds seven", "sm like", "like proteins", "proteins and", "and its", "its assembly", "assembly does", "does not", "not involve", "involve a", "a cytoplasmic", "cytoplasmic phase.", "phase. the", "the snrnp", "snrnp biogenesis", "biogenesis pathway", "pathway for", "for all", "all of", "of the", "snrnas is", "is complex", "involving nuclear", "nuclear export", "export of", "of snrna", "sm core", "core assembly", "assembly in", "in the", "the cytoplasm", "cytoplasm and", "and re", "re import", "import of", "the mature", "mature snrnp.", "snrnp. the", "the assembly", "assembly of", "the snrna:sm", "snrna:sm core", "core is", "is carried", "carried out", "out by", "by the", "the survival", "survival of", "of motor", "motor neurons", "complex. the", "the smn", "smn 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complex.", "smn complex. the smn", "complex. the smn complex stringently", "the smn complex stringently scrutinizes", "smn complex stringently scrutinizes rnas", "complex stringently scrutinizes rnas for", "stringently scrutinizes rnas for specific", "scrutinizes rnas for specific features", "rnas for specific features that", "for specific features that define", "specific features that define them", "features that define them as", "that define them as snrnas", "define them as snrnas and", "them as snrnas and binds", "as snrnas and binds the", "snrnas and binds the rna", "and binds the rna binding", "binds the rna binding sm", "the rna binding sm proteins." ] }, { "record_id": "GLY_000594_1_157", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "192905", "r hsa", "hsa 192905", "r hsa 192905" ] }, { "record_id": "GLY_000594_1_157", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "vrnp assembly", "for each", "each of", "of eight", "eight gene", "gene segments", "a viral", "viral ribonucleoprotein", "containing a", "viral negative", "negative sense", "sense rna", "segment complexed", "complexed with", "with nucleoprotein", "and the", "the trimeric", "trimeric influenza", "influenza polymerase", "and pa", "is assembled", "assembled in", "in the", "the nucleus", "reviewed in", "in buolo", "2006 .", "the vrnp", "vrnp functions", "functions in", "in three", "three modes", "in mikulasova", "2004 :", "which synthesizes", "synthesizes viral", "viral messenger", "messenger rna", "rna from", "from the", "the vrna", "vrna template", "template using", "using as", "as primers", "primers 5'", "5' ends", "ends of", "of cellular", "cellular mrnas", "mrnas containing", "containing the", "the cap", "which produces", "produces positive", "positive sense", "sense complementary", "complementary rna", "and subsequently", "subsequently vrna", "both complexed", "with np", "np and", "trimeric 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phosphorylation", "mediated phosphorylation at", "phosphorylation at thr41", "thr41 ser37", "ser37 and ser33", "ser33 amit", "amit et al.", "al. 2002", "lui et al.", "degradation of beta catenin", "of beta catenin is", "beta catenin is initiated", "catenin is initiated following", "is initiated following amino", "initiated following amino terminal", "following amino terminal serine/threonine", "amino terminal serine/threonine phosphorylation.", "terminal serine/threonine phosphorylation. phosphorylation", "serine/threonine phosphorylation. phosphorylation of", "phosphorylation. phosphorylation of b", "phosphorylation of b catenin", "of b catenin at", "catenin at s45", "at s45 by", "s45 by ck1 alpha", "by ck1 alpha primes", "ck1 alpha primes the", "alpha primes the subsequent", "primes the subsequent sequential", "the subsequent sequential gsk", "subsequent sequential gsk 3", "sequential gsk 3 mediated", "gsk 3 mediated phosphorylation", "3 mediated phosphorylation at", "mediated phosphorylation at thr41", "at thr41 ser37", "thr41 ser37 and", "and ser33 amit", "ser33 amit et", "et al. 2002", "2002 lui", "al. 2002 .", "degradation of beta catenin is", "of beta catenin is initiated", "beta catenin is initiated following", "catenin is initiated following amino", "is initiated following amino terminal", "initiated following amino terminal serine/threonine", "following amino terminal serine/threonine phosphorylation.", "amino terminal serine/threonine phosphorylation. phosphorylation", "terminal serine/threonine phosphorylation. phosphorylation of", "serine/threonine phosphorylation. phosphorylation of b", "phosphorylation. phosphorylation of b catenin", "phosphorylation of b catenin at", "b catenin at s45", "catenin at s45 by", "at s45 by ck1", "s45 by ck1 alpha primes", "by ck1 alpha primes the", "ck1 alpha primes the subsequent", "alpha primes the subsequent sequential", "primes the subsequent sequential gsk", "the subsequent sequential gsk 3", "subsequent sequential gsk 3 mediated", "sequential gsk 3 mediated phosphorylation", "gsk 3 mediated phosphorylation at", "3 mediated phosphorylation at thr41", "phosphorylation at thr41 ser37", "at thr41 ser37 and", "thr41 ser37 and ser33", "ser37 and ser33 amit", "and ser33 amit et", "ser33 amit et al.", "amit et al. 2002", "2002 lui et", "lui et al. 2002", "et al. 2002 ." ] }, { "record_id": "GLY_000594_1_166", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1963640", "r hsa", "hsa 1963640", "r hsa 1963640" ] }, { "record_id": "GLY_000594_1_166", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "grb2 events", "events in", "in erbb2", "erbb2 signaling", "grb2 events in", "events in erbb2", "in erbb2 signaling", "grb2 events in erbb2", "events in erbb2 signaling", "grb2 events in erbb2 signaling", "erbb2:egfr and", "and erbb2:erbb4", "erbb2:erbb4 can", "can directly", "directly recruit", "recruit grb2:sos1", "grb2:sos1 complex", "complex through", "through phosphorylated", "phosphorylated c", "c tail", "tail tyrosines", "tyrosines of", "of egfr", "y1068 and", "and y1086", "and erbb2", "that serve", "serve as", "as docking", "docking sites", "sites for", "for grb2", "xie et", "et al.", "al. 1995", "sepp lorenzino", "lorenzino et", "al. 1996", "results in", "in sos1", "sos1 mediated", "mediated guanyl", "guanyl nucleotide", "nucleotide exchange", "exchange on", "on ras", "ras and", "and activation", "activation of", "of raf", "raf and", "and map", "map kinases", "janes et", "al. 1994", "1996 .", "erbb2:egfr and erbb2:erbb4", "and erbb2:erbb4 can", "erbb2:erbb4 can directly", "can directly recruit", "directly recruit grb2:sos1", "recruit grb2:sos1 complex", "grb2:sos1 complex through", "complex through phosphorylated", "through phosphorylated c", "phosphorylated c tail", "c tail tyrosines", "tail tyrosines of", "tyrosines of egfr", "egfr y1068", "y1068 and y1086", "y1086 and", "erbb2 y1139", "y1139 that", "that serve as", "serve as docking", "as docking sites", "docking sites for", "sites for grb2", "grb2 xie", "xie et al.", "et al. 1995", "1995 sepp", "sepp lorenzino et", "lorenzino et al.", "et al. 1996", "which again", "again results", "results in sos1", "in sos1 mediated", "sos1 mediated guanyl", "mediated guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange on", "exchange on ras", "on ras and", "ras and activation", "and activation of", "activation of raf", "of raf and", "raf and map", "and map kinases", "kinases janes", "janes et al.", "et al. 1994", "1994 sepp", "al. 1996 .", "erbb2:egfr and erbb2:erbb4 can", "and erbb2:erbb4 can directly", "erbb2:erbb4 can directly recruit", "can directly recruit grb2:sos1", "directly recruit grb2:sos1 complex", "recruit grb2:sos1 complex through", "grb2:sos1 complex through phosphorylated", "complex through phosphorylated c", "through phosphorylated c tail", "phosphorylated c tail tyrosines", "c tail tyrosines of", "tail tyrosines of egfr", "of egfr y1068", "egfr y1068 and", "and y1086 and", "y1086 and erbb2", "and erbb2 y1139", "y1139 that serve", "that serve as docking", "serve as docking sites", "as docking sites for", "docking sites for grb2", "for grb2 xie", "grb2 xie et", "xie et al. 1995", "al. 1995 sepp", "1995 sepp lorenzino", "sepp lorenzino et al.", "lorenzino et al. 1996", "1996 which", "again results in", "results in sos1 mediated", "in sos1 mediated guanyl", "sos1 mediated guanyl nucleotide", "mediated guanyl nucleotide exchange", "guanyl nucleotide exchange on", "nucleotide exchange on ras", "exchange on ras and", "on ras and activation", "ras and activation of", "and activation of raf", "activation of raf and", "of raf and map", "raf and map kinases", "map kinases janes", "kinases janes et", "janes et al. 1994", "al. 1994 sepp", "1994 sepp lorenzino", "et al. 1996 .", "erbb2:egfr and erbb2:erbb4 can directly", "and erbb2:erbb4 can directly recruit", "erbb2:erbb4 can directly recruit grb2:sos1", "can directly recruit grb2:sos1 complex", "directly recruit grb2:sos1 complex through", "recruit grb2:sos1 complex through phosphorylated", "grb2:sos1 complex through phosphorylated c", "complex through phosphorylated c tail", "through phosphorylated c tail tyrosines", "phosphorylated c tail tyrosines of", "c tail tyrosines of egfr", "tyrosines of egfr y1068", "of egfr y1068 and", "egfr y1068 and y1086", "y1068 and y1086 and", "and y1086 and erbb2", "erbb2 y1139 that", "y1139 that serve as", "that serve as docking sites", "serve as docking sites for", "as docking sites for grb2", "sites for grb2 xie", "for grb2 xie et", "grb2 xie et al.", "et al. 1995 sepp", "al. 1995 sepp lorenzino", "1995 sepp lorenzino et", "sepp lorenzino et al. 1996", "al. 1996 which", "which again results", "again results in sos1", "results in sos1 mediated guanyl", "in sos1 mediated guanyl nucleotide", "sos1 mediated guanyl nucleotide exchange", "mediated guanyl nucleotide exchange on", "guanyl nucleotide exchange on ras", "nucleotide exchange on ras and", "exchange on ras and activation", "on ras and activation of", "ras and activation of raf", "and activation of raf and", "activation of raf and map", "of raf and map kinases", "and map kinases janes", "map kinases janes et", "kinases janes et al.", "et al. 1994 sepp", "al. 1994 sepp lorenzino", "1994 sepp lorenzino et", "lorenzino et al. 1996 ." ] }, { "record_id": "GLY_000594_1_167", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1963642", "r hsa", "hsa 1963642", "r hsa 1963642" ] }, { "record_id": "GLY_000594_1_167", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi3k events", "events in", "in erbb2", "erbb2 signaling", "pi3k events in", "events in erbb2", "in erbb2 signaling", "pi3k events in erbb2", "events in erbb2 signaling", "pi3k events in erbb2 signaling", "erbb2:erbb3 and", "and erbb2:erbb4cyt1", "erbb2:erbb4cyt1 heterodimers", "heterodimers activate", "activate pi3k", "pi3k signaling", "signaling by", "by direct", "direct binding", "binding of", "of pi3k", "pi3k regulatory", "regulatory subunit", "subunit p85", "yang et", "et al.", "al. 2007", "cohen et", "al. 1996", "kaushansky et", "al. 2008", "to phosphorylated", "phosphorylated tyrosine", "tyrosine residues", "residues in", "in the", "the c", "c tail", "tail of", "of erbb3", "y1276 and", "and y1289", "and erbb4", "erbb4 cyt1", "cyt1 isoforms", "y1056 in", "in jm", "jm a", "a cyt1", "cyt1 isoform", "isoform and", "and y1046", "y1046 in", "jm b", "b cyt1", "isoform .", ". regulatory", "p85 subsequently", "subsequently recruits", "recruits catalytic", "catalytic subunit", "subunit p110", "p110 of", "resulting in", "the formation", "formation of", "of active", "active pi3k", "conversion of", "of pip2", "pip2 to", "to pip3", "and pip3", "pip3 mediated", "mediated activation", "activation of", "of akt", "akt signaling", "junttila et", "al. 2009", "kainulainen et", "al. 2000", "2000 .", ". heterodimers", "heterodimers of", "of erbb2", "erbb2 and", "and egfr", "egfr recruit", "recruit pi3k", "pi3k indirectly", "through grb2:gab1", "grb2:gab1 complex", "jackson et", "al. 2004", "which again", "again leads", "leads to", "akt signaling.", "erbb2:erbb3 and erbb2:erbb4cyt1", "and erbb2:erbb4cyt1 heterodimers", "erbb2:erbb4cyt1 heterodimers activate", "heterodimers activate pi3k", "activate pi3k signaling", "pi3k signaling by", "signaling by direct", "by direct binding", "direct binding of", "binding of pi3k", "of pi3k regulatory", "pi3k regulatory subunit", "regulatory subunit p85", "p85 yang", "yang et al.", "et al. 2007", "2007 cohen", "cohen et al.", "et al. 1996", "1996 kaushansky", "kaushansky et al.", "et al. 2008", "2008 to", "to phosphorylated tyrosine", "phosphorylated tyrosine residues", "tyrosine residues in", "residues in the", "in the c", "the c tail", "c tail of", "tail of erbb3", "erbb3 y1054", "y1054 y1197", "y1197 y1222", "y1222 y1224", "y1224 y1276", "y1276 and y1289", "y1289 and", "and erbb4 cyt1", "erbb4 cyt1 isoforms", "isoforms y1056", "y1056 in jm", "in jm a", "jm a cyt1", "a cyt1 isoform", "cyt1 isoform and", "isoform and y1046", "and y1046 in", "y1046 in jm", "in jm b", "jm b cyt1", "b cyt1 isoform", "cyt1 isoform .", "isoform . regulatory", ". regulatory subunit", "subunit p85 subsequently", "p85 subsequently recruits", "subsequently recruits catalytic", "recruits catalytic subunit", "catalytic subunit p110", "subunit p110 of", "p110 of pi3k", "pi3k resulting", "resulting in the", "in the formation", "the formation of", "formation of active", "of active pi3k", "pi3k conversion", "conversion of pip2", "of pip2 to", "pip2 to pip3", "pip3 and", "and pip3 mediated", "pip3 mediated activation", "mediated activation of", "activation of akt", "of akt signaling", "signaling junttila", "junttila et al.", "et al. 2009", "2009 kainulainen", "kainulainen et al.", "et al. 2000", "al. 2000 .", "2000 . heterodimers", ". heterodimers of", "heterodimers of erbb2", "of erbb2 and", "erbb2 and egfr", "and egfr recruit", "egfr recruit pi3k", "recruit pi3k indirectly", "indirectly through", "through grb2:gab1 complex", "complex jackson", "jackson et al.", "et al. 2004", "which again leads", "again leads to", "leads to pip3", "to pip3 mediated", "of akt signaling.", "erbb2:erbb3 and erbb2:erbb4cyt1 heterodimers", "and erbb2:erbb4cyt1 heterodimers activate", "erbb2:erbb4cyt1 heterodimers activate pi3k", "heterodimers activate pi3k signaling", "activate pi3k signaling by", "pi3k signaling by direct", "signaling by direct binding", "by direct binding of", "direct binding of pi3k", "binding of pi3k regulatory", "of pi3k regulatory subunit", "pi3k regulatory subunit p85", "subunit p85 yang", "p85 yang et", "yang et al. 2007", "al. 2007 cohen", "2007 cohen et", "cohen et al. 1996", "al. 1996 kaushansky", "1996 kaushansky et", "kaushansky et al. 2008", "al. 2008 to", "2008 to phosphorylated", "to phosphorylated tyrosine residues", "phosphorylated tyrosine residues in", "tyrosine residues in the", "residues in the c", "in the c tail", "the c tail of", "c tail of erbb3", "of erbb3 y1054", "y1224 y1276 and", "and y1289 and", "y1289 and erbb4", "and erbb4 cyt1 isoforms", "cyt1 isoforms y1056", "isoforms y1056 in", "y1056 in jm a", "in jm a cyt1", "jm a cyt1 isoform", "a cyt1 isoform and", "cyt1 isoform and y1046", "isoform and y1046 in", "and y1046 in jm", "y1046 in jm b", "in jm b cyt1", "jm b cyt1 isoform", "b cyt1 isoform .", "cyt1 isoform . regulatory", "isoform . regulatory subunit", ". regulatory subunit p85", "regulatory subunit p85 subsequently", "subunit p85 subsequently recruits", "p85 subsequently recruits catalytic", "subsequently recruits catalytic subunit", "recruits catalytic subunit p110", "catalytic subunit p110 of", "subunit p110 of pi3k", "of pi3k resulting", "pi3k resulting in", "resulting in the formation", "in the formation of", "the formation of active", "formation of active pi3k", "active pi3k conversion", "pi3k conversion of", "conversion of pip2 to", "of pip2 to pip3", "to pip3 and", "pip3 and pip3", "and pip3 mediated activation", "pip3 mediated activation of", "mediated activation of akt", "activation of akt signaling", "akt signaling junttila", "signaling junttila et", "junttila et al. 2009", "al. 2009 kainulainen", "2009 kainulainen et", "kainulainen et al. 2000", "et al. 2000 .", "al. 2000 . heterodimers", "2000 . heterodimers of", ". heterodimers of erbb2", "heterodimers of erbb2 and", "of erbb2 and egfr", "erbb2 and egfr recruit", "and egfr recruit pi3k", "egfr recruit pi3k indirectly", "pi3k indirectly through", "indirectly through grb2:gab1", "grb2:gab1 complex jackson", "complex jackson et", "jackson et al. 2004", "2004 which", "which again leads to", "again leads to pip3", "leads to pip3 mediated", "to pip3 mediated activation", "activation of akt signaling.", "erbb2:erbb3 and erbb2:erbb4cyt1 heterodimers activate", "and erbb2:erbb4cyt1 heterodimers activate pi3k", "erbb2:erbb4cyt1 heterodimers activate pi3k signaling", "heterodimers activate pi3k signaling by", "activate pi3k signaling by direct", "pi3k signaling by direct binding", "signaling by direct binding of", "by direct binding of pi3k", "direct binding of pi3k regulatory", "binding of pi3k regulatory subunit", "of pi3k regulatory subunit p85", "regulatory subunit p85 yang", "subunit p85 yang et", "p85 yang et al.", "et al. 2007 cohen", "al. 2007 cohen et", "2007 cohen et al.", "et al. 1996 kaushansky", "al. 1996 kaushansky et", "1996 kaushansky et al.", "et al. 2008 to", "al. 2008 to phosphorylated", "2008 to phosphorylated tyrosine", "to phosphorylated tyrosine residues in", "phosphorylated tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "in the c tail of", "the c tail of erbb3", "tail of erbb3 y1054", "erbb3 y1054 y1197", "y1054 y1197 y1222", "y1197 y1222 y1224", "y1222 y1224 y1276", "y1224 y1276 and y1289", "y1276 and y1289 and", "and y1289 and erbb4", "y1289 and erbb4 cyt1", "erbb4 cyt1 isoforms y1056", "cyt1 isoforms y1056 in", "isoforms y1056 in jm", "y1056 in jm a cyt1", "in jm a cyt1 isoform", "jm a cyt1 isoform and", "a cyt1 isoform and y1046", "cyt1 isoform and y1046 in", "isoform and y1046 in jm", "and y1046 in jm b", "y1046 in jm b cyt1", "in jm b cyt1 isoform", "jm b cyt1 isoform .", "b cyt1 isoform . regulatory", "cyt1 isoform . regulatory subunit", "isoform . regulatory subunit p85", ". regulatory subunit p85 subsequently", "regulatory subunit p85 subsequently recruits", "subunit p85 subsequently recruits catalytic", "p85 subsequently recruits catalytic subunit", "subsequently recruits catalytic subunit p110", "recruits catalytic subunit p110 of", "catalytic subunit p110 of pi3k", "p110 of pi3k resulting", "of pi3k resulting in", "pi3k resulting in the", "resulting in the formation of", "in the formation of active", "the formation 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2 genes involved", "in fatty acid transport", "acid transport cd36", "
3 genes involved", "genes involved in producing", "involved in producing fatty", "in producing fatty acids", "producing fatty acids and", "fatty acids and very", "acids and very low", "and very low density", "very low density lipoproteins", "density lipoproteins me1", "
4 genes encoding", "encoding apolipoproteins apoa1", "
5 genes involved", "genes involved in triglyceride", "involved in triglyceride clearance", "clearance angptl4", "
6 genes involved", "genes involved in glycerol", "involved in glycerol metabolism", "glycerol metabolism gpd1", "metabolism gpd1 in", "in mouse
7", "
7 genes involved", "genes involved in glucose", "involved in glucose metabolism", "glucose metabolism pdk4", "
8 genes involved", "genes involved in peroxisome", "involved in peroxisome proliferation", "peroxisome proliferation pex11a", "
9 genes involved", "genes involved in lipid", "involved in lipid storage", "lipid storage plin", "plin adfp .
many", "adfp .
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2", "hmgcs2
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3", "cpt2
3 genes", "
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4", "scd1
4 genes", "
4 genes encoding apolipoproteins", "genes encoding apolipoproteins apoa1", "apolipoproteins apoa1 apoa2", "apoa1 apoa2 apoa5", "apoa2 apoa5
5", "apoa5
5 genes", "
5 genes involved in", "genes involved in triglyceride clearance", "triglyceride clearance angptl4", "angptl4
6 genes", "
6 genes involved in", "genes involved in glycerol metabolism", "in glycerol metabolism gpd1", "glycerol metabolism gpd1 in", "metabolism gpd1 in mouse", "gpd1 in mouse
7", "mouse
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8", "pdk4
8 genes", "
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9", "pex11a
9 genes", "
9 genes involved in", "genes involved in lipid storage", "in lipid storage plin", "storage plin adfp", "plin adfp .
many other", "adfp .
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slc27a4 many", "slc27a4 many acot genes", "many acot genes and", "acot genes and others", "and others reviewed in", "others reviewed in rakhshandehroo", "reviewed in rakhshandehroo et al.", "in rakhshandehroo et al. 2010", "rakhshandehroo et al. 2010 ." ] }, { "record_id": "GLY_000594_1_175", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "199220", "r hsa", "hsa 199220", "r hsa 199220" ] }, { "record_id": "GLY_000594_1_175", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "vitamin b5", "b5 pantothenate", "pantothenate metabolism", "vitamin b5 pantothenate", "b5 pantothenate metabolism", "is an", "an essential", "essential precursor", "precursor for", "for the", "the synthesis", "synthesis of", "of the", "the metabolic", "metabolic cofactor", "cofactor coenzyme", "coenzyme a", "coa sh", "robishaw and", "and neely", "neely 1985", "and is", "is the", "the prosthetic", "prosthetic group", "group 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there at", "plasma membrane. there at least", "membrane. there at least two", "there at least two classes", "at least two classes of", "least two classes of clathrin", "two classes of clathrin coated", "classes of clathrin coated vesicles", "of clathrin coated vesicles in", "clathrin coated vesicles in cells", "vesicles in cells one", "in cells one predominantly", "cells one predominantly golgi", "predominantly golgi associated involved", "golgi associated involved in", "associated involved in budding", "involved in budding from the", "in budding from the trans", "budding from the trans golgi", "from the trans golgi network", "the trans golgi network and", "trans golgi network and the", "golgi network and the other", "network and the other at", "and the other at the", "the other at the plasma", "other at the plasma membrane.", "at the plasma membrane. here", "the plasma membrane. here the", "plasma membrane. here the clathrin", "membrane. here the clathrin coated", "here the clathrin coated vesicles", "the clathrin coated vesicles emerging", "clathrin coated vesicles emerging from", "coated vesicles emerging from the", "vesicles emerging from the golgi", "emerging from the golgi apparatus", "from the golgi apparatus are", "the golgi apparatus are triggered", "golgi apparatus are triggered by", "apparatus are triggered by the", "are triggered by the heterotetrameric", "triggered by the heterotetrameric adaptor", "by the heterotetrameric adaptor protein", "the heterotetrameric adaptor protein complex", "adaptor protein complex ap", "protein complex ap 1", "complex ap 1 at", "ap 1 at the trans", "1 at the trans golgi", "at the trans golgi network", "the trans golgi network membrane.", "trans golgi network membrane. the", "golgi network membrane. the cargo", "network membrane. the cargo can", "membrane. the cargo can be", "the cargo can be transmembrane", "can be transmembrane membrane", "be transmembrane membrane associated", "transmembrane membrane associated or", "membrane associated or golgi luminal", "associated or golgi luminal proteins.", "or golgi luminal proteins. each", "golgi luminal proteins. each step", "luminal proteins. each step in", "proteins. each step in the", "each step in the vesicle", "step in the vesicle sculpting", "in the vesicle sculpting pathway", "vesicle sculpting pathway gathers", "sculpting pathway gathers cargo", "pathway gathers cargo and", "gathers cargo and clathrin triskeletons", "and clathrin triskeletons until", "clathrin triskeletons until a", "triskeletons until a complete", "until a complete vesicular sphere", "a complete vesicular sphere is", "complete vesicular sphere is formed.", "vesicular sphere is formed. with", "sphere is formed. with the", "is formed. with the scission", "formed. with the scission of", "with the scission of the", "the scission of the membrane", "scission of the membrane the", "of the membrane the vesicle", "the membrane the vesicle is", "membrane the vesicle is released", "the vesicle is released and", "vesicle is released and eventually", "is released and eventually losses", "released and eventually losses its", "and eventually losses its clathrin", "eventually losses its clathrin coat." ] }, { "record_id": "GLY_000594_1_177", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "200425", "r hsa", "hsa 200425", "r hsa 200425" ] }, { "record_id": "GLY_000594_1_177", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "carnitine shuttle", "the mitochondrial", "mitochondrial carnitine", "carnitine system", "system catalyzes", "catalyzes the", "the transport", "transport of", "of long", "long chain", "chain fatty", "fatty acids", "into the", "mitochondrial matrix", "matrix where", "where they", "they undergo", "undergo beta", "beta oxidation.", "oxidation. this", "this transport", "transport system", "system consists", "consists of", "of the", "the malonyl", "malonyl coa", "coa sensitive", "sensitive carnitine", "carnitine palmitoyltransferase", "palmitoyltransferase i", "cpt i", "localized in", "in the", "mitochondrial outer", "outer membrane", "the carnitine:acylcarnitine", "carnitine:acylcarnitine translocase", "an integral", "integral inner", "inner membrane", "membrane protein", "and carnitine", "palmitoyltransferase ii", "ii localized", "localized on", "on the", "the matrix", "matrix side", "side of", "the inner", "inner membrane.", "kerner &", "& hoppel", "ramsay et", "et al.", "al. 2001", "2001 .", ". additional", "additional reactions", "reactions annotated", "annotated here", "here enable", "enable the", "the uptake", "uptake of", "of carnitine", "carnitine and", "and the", "the regulation", "regulation of", "of fatty", "fatty acid", "acid biosynthesis", "biosynthesis at", "at the", "the level", "level of", "of acaca", "acaca and", "and acacb", "acacb to", "to minimize", "minimize simultaeous", "simultaeous mitochondrial", "mitochondrial catabolism", "catabolism and", "and cytosolic", "cytosolic biosynthesis", "biosynthesis of", "fatty acids.", "the mitochondrial carnitine", "mitochondrial carnitine system", "carnitine system catalyzes", "system catalyzes the", "catalyzes the transport", "the transport of", "transport of long", "of long chain", "long chain fatty", "chain fatty acids", "acids into", "into the mitochondrial", "the mitochondrial matrix", "mitochondrial matrix where", "matrix where they", "where they undergo", "they undergo beta", "undergo beta oxidation.", "beta oxidation. this", "oxidation. this transport", "this transport system", "transport system consists", "system consists of", "consists of the", "of the malonyl", "the malonyl coa", "malonyl coa sensitive", "coa sensitive carnitine", "sensitive carnitine palmitoyltransferase", "carnitine palmitoyltransferase i", "i cpt", "i localized", "localized in the", "in the mitochondrial", "the mitochondrial outer", "mitochondrial outer membrane", "membrane 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kerner &", "& hoppel 2000", "2000 ramsay et", "ramsay et al. 2001", "et al. 2001 .", "al. 2001 . additional", "2001 . additional reactions", ". additional reactions annotated", "additional reactions annotated here", "reactions annotated here enable", "annotated here enable the", "here enable the uptake", "enable the uptake of", "the uptake of carnitine", "uptake of carnitine and", "of carnitine and the", "carnitine and the regulation", "and the regulation of", "the regulation of fatty", "regulation of fatty acid", "of fatty acid biosynthesis", "fatty acid biosynthesis at", "acid biosynthesis at the", "biosynthesis at the level", "at the level of", "the level of acaca", "level of acaca and", "of acaca and acacb", "acaca and acacb to", "and acacb to minimize", "acacb to minimize simultaeous", "to minimize simultaeous mitochondrial", "minimize simultaeous mitochondrial catabolism", "simultaeous mitochondrial catabolism and", "mitochondrial catabolism and cytosolic", "catabolism and cytosolic biosynthesis", "and cytosolic biosynthesis of", "cytosolic biosynthesis of long", "biosynthesis of long chain", "long chain fatty acids.", "the mitochondrial carnitine system catalyzes", "mitochondrial carnitine system catalyzes the", "carnitine system catalyzes the transport", "system catalyzes the transport of", "catalyzes the transport of long", "the transport of long chain", "transport of long chain fatty", "of long chain fatty acids", "chain fatty acids into", "fatty acids into the", "acids into the mitochondrial", "into the mitochondrial matrix where", "the mitochondrial matrix where they", "mitochondrial matrix where they undergo", "matrix where they undergo beta", "where they undergo beta oxidation.", "they undergo beta oxidation. this", "undergo beta oxidation. this transport", "beta oxidation. this transport system", "oxidation. this transport system consists", "this transport system consists of", "transport system consists of the", "system consists of the malonyl", "consists of the malonyl coa", "of the malonyl coa sensitive", "the malonyl coa sensitive carnitine", "malonyl coa sensitive carnitine palmitoyltransferase", "coa sensitive carnitine palmitoyltransferase i", "carnitine palmitoyltransferase i cpt", "palmitoyltransferase i cpt i", "cpt i localized in", "i localized in the", "localized in the mitochondrial outer", "in the mitochondrial outer membrane", "mitochondrial outer membrane the", "outer membrane the carnitine:acylcarnitine", "membrane the carnitine:acylcarnitine translocase", "the carnitine:acylcarnitine translocase an", "carnitine:acylcarnitine translocase an integral", "translocase an integral inner", "an integral inner membrane protein", "inner membrane protein and", "membrane protein and carnitine", "protein and carnitine palmitoyltransferase", "and carnitine palmitoyltransferase ii localized", "carnitine palmitoyltransferase ii localized on", "palmitoyltransferase ii localized on the", "ii localized on the matrix", "localized on the matrix side", "on the matrix side of", "the matrix side of the", "matrix side of the inner", "side of the inner membrane.", "the inner membrane. kerner", "inner membrane. kerner &", "membrane. kerner & hoppel", "kerner & hoppel 2000", "hoppel 2000 ramsay", "2000 ramsay et al.", "ramsay et al. 2001 .", "et al. 2001 . additional", "al. 2001 . additional reactions", "2001 . additional reactions annotated", ". additional reactions annotated here", "additional reactions annotated here enable", "reactions annotated here enable the", "annotated here enable the uptake", "here enable the uptake of", "enable the uptake of carnitine", "the uptake of carnitine and", "uptake of carnitine and the", "of carnitine and the regulation", "carnitine and the regulation of", "and the regulation of fatty", "the regulation of fatty acid", "regulation of fatty acid biosynthesis", "of fatty acid biosynthesis at", "fatty acid biosynthesis at the", "acid biosynthesis at the level", "biosynthesis at the level of", "at the level of acaca", "the level of acaca and", "level of acaca and acacb", "of acaca and acacb to", "acaca and acacb to minimize", "and acacb to minimize simultaeous", "acacb to minimize simultaeous mitochondrial", "to minimize simultaeous mitochondrial catabolism", "minimize simultaeous mitochondrial catabolism and", "simultaeous mitochondrial catabolism and cytosolic", "mitochondrial catabolism and cytosolic biosynthesis", "catabolism and cytosolic biosynthesis of", "and cytosolic biosynthesis of long", "cytosolic biosynthesis of long chain", "biosynthesis of long chain fatty", "of long chain fatty acids." ] }, { "record_id": "GLY_000594_1_178", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "201451", "r hsa", "hsa 201451", "r hsa 201451" ] }, { "record_id": "GLY_000594_1_178", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by bmp", "signaling by bmp", "bone morphogenetic", "morphogenetic proteins", "have many", "many biological", "biological activities", "activities in", "in various", "various tissues", "including bone", "blood vessels", "liver and", "and lung.", "lung. they", "they are", "are members", "members of", "of the", "the transforming", "transforming growth", "growth factor", "factor beta", "family. they", "they bind", "bind to", "to type", "type ii", "ii and", "and type", "type i", "i serine", "serine threonine", "threonine kinase", "kinase receptors", "which transduce", "transduce signals", "signals through", "through smad", "smad and", "and non", "non smad", "smad signalling", "signalling pathways.", "pathways. bmp", "bmp signalling", "signalling is", "is linked", "linked to", "to a", "a wide", "wide variety", "variety of", "of clinical", "clinical disorders", "including vascular", "vascular diseases", "skeletal diseases", "diseases and", "and cancer.", "cancer. bmps", "bmps typically", "typically activate", "activate bmp", "bmp type", "i receptors", "receptors and", "and signal", "signal via", "via smad1", "5 and", "and 8.", "8. they", "they can", "can be", "be classified", "classified into", "into several", "several subgroups", "including the", "the bmp2/4", "bmp2/4 group", "the bmp5", "bmp5 8", "8 osteogenic", "osteogenic protein", "protein 1", "the growth", "growth and", "and differentiation", "differentiation factor", "5 7", "7 group", "group and", "and the", "the bmp9/10", "bmp9/10 group.", "group. most", "most of", "the proteins", "proteins of", "op1 and", "and bmp9/10", "bmp9/10 groups", "groups induce", "induce formation", "formation of", "of bone", "bone and", "and cartilage", "cartilage tissues", "tissues in", "in vivo", "while the", "the gdf5", "gdf5 7", "group induce", "induce cartilage", "cartilage and", "and tendon", "tendon like", "but not", "not bone", "bone like", "miyazono et", "et al.", "al. 2010", "2010 .", ". members", "the tgfb", "tgfb family", "family bind", "to two", "two types", "types of", "of serine", "i and", "massagu\u00e9 2012", "2012 .", ". bmps", "bmps can", "can bind", "bind type", "receptors in", "in the", "the absence", "absence of", "of type", "ii receptors", "but both", "both types", "types are", "are required", "required for", "for signal", "signal transduction.", "transduction. the", "the presence", "presence of", "of both", "types dramatically", "dramatically increases", "increases binding", "binding affinity", "rozenweig et", "al. 1995", "1995 .", ". the", "the type", "ii receptor", "receptor kinase", "kinase transphosphorylates", "transphosphorylates the", "i receptor", "which transmits", "transmits specific", "specific intracellular", "intracellular signals.", "signals. type", "receptors share", "share similar", "similar structural", "structural properties", "comprised of", "of a", "a relatively", "relatively short", "short extracellular", "extracellular domain", "a single", "single membrane", "membrane spanning", "spanning domain", "domain and", "and an", "an intracellular", "intracellular domain", "domain containing", "containing a", "a serine", "kinase domain.", "domain. seven", "seven receptors", "collectively referred", "referred to", "to as", "as the", "the activin", "activin receptor", "receptor like", "like kinases", "have been", "been identified", "identified as", "as type", "receptors for", "for the", "family in", "in mammals.", "mammals. alks", "alks are", "are classified", "into three", "three groups", "groups based", "based on", "on their", "their structure", "structure and", "and function", "the bmpri", "bmpri group", "morphogenetic protein", "protein receptor", "receptor type", "type 1a", "bmpr1a and", "and bone", "type 1b", "the alk1", "alk1 group", "serine/threonine protein", "protein kinase", "kinase receptor", "receptor r3", "acvrl1 and", "and activin", "type 1", "the tbetar1", "tbetar1 group", "acvr1b and", "tgf beta", "beta receptor", "tgfbr1 and", "type 1c", "kawabata et", "al. 1998", "1998 .", ". alk1", "and bmpri", "group activate", "activate smad1/5/8", "smad1/5/8 and", "and transduce", "transduce similar", "similar intracellular", "signals. the", "activate smad2/3.", "smad2/3. bmpr1a", "and acvr1", "acvr1 are", "are widely", "widely expressed.", "expressed. bmpr1b", "bmpr1b shows", "shows a", "a more", "more restricted", "restricted expression", "expression profile.", "profile. acvrl1", "acvrl1 is", "is limited", "limited to", "to endothelial", "endothelial cells", "cells and", "and a", "a few", "few other", "other cell", "cell types.", "types. the", "the binding", "binding specificities", "specificities of", "of bmps", "bmps to", "receptors is", "is affected", "affected by", "by the", "receptors that", "that are", "are present", "yu et", "al. 2005", "2005 .", ". typically", "bmp2 and", "and bmp4", "bmp4 bind", "to bmpr1a", "and bmpr1b", "ten dijke", "dijke et", "al. 1994", "1994 .", ". bmp6", "bmp6 and", "and bmp7", "bmp7 bind", "bind strongly", "strongly to", "to acvr1", "acvr1 and", "and weakly", "weakly to", "to bmpr1b.", "bmpr1b. growth/differentiation", "growth/differentiation factor", "factor 5", "preferentially binds", "binds to", "to bmpr1b", "not to", "to other", "other type", "nishitoh et", ". bmp9", "bmp9 and", "and bmp10", "bmp10 bind", "to acvrl1", "and acvrl", "scharpfenecker et", "al. 2007", "2007 .", ". bmp", "receptors are", "are shared", "shared by", "by other", "other members", "tgfb family.", "family. three", "three receptors", "type 2", "type 2a", "type 2b", "are the", "for mammalian", "mammalian bmps.", "bmps. they", "widely expressed", "expressed in", "various tissues.", "tissues. bmpr2", "bmpr2 is", "is specific", "specific for", "for bmps", "whereas acvr2a", "acvr2a and", "and acvr2b", "acvr2b are", "shared with", "with activins", "activins and", "and myostatin.", "myostatin. bmp", "bmp binding", "binding and", "and signalling", "signalling can", "be affected", "by coreceptors.", "coreceptors. glycosylphosphatidylinositol", "anchored proteins", "the repulsive", "repulsive guidance", "guidance molecule", "including rgma", "and hemojuvelin", "are coreceptors", "coreceptors for", "for bmp2", "enhancing signaling", "samad et", "babitt et", "2006 .", ". they", "they interact", "interact with", "with bmp", "i and/or", "and/or type", "and bind", "bind bmp2", "not bmp7", "bmp7 or", "or tgfb1.", "tgfb1. bmp2/4", "bmp2/4 signalling", "signalling normally", "normally involves", "involves bmpr2", "not acvr2a", "acvr2a or", "or acvr2b.", "acvr2b. cells", "cells transfected", "transfected with", "with rgma", "rgma use", "use both", "both bmpr2", "bmpr2 and", "and acvr2a", "acvr2a for", "for bmp", "bmp 2/4", "2/4 signalling", "suggesting that", "that rgma", "rgma facilitates", "facilitates the", "the use", "use of", "of acvr2a", "acvr2a by", "by bmp2/4", "xia et", ". endoglin", "is a", "a transmembrane", "transmembrane protein", "protein expressed", "in proliferating", "proliferating endothelial", "endothelial cells.", "cells. it", "it binds", "binds various", "various ligands", "ligands including", "including tgfb1/3", "activin a", "a and", "and bmp2/7", "barbara et", "al. 1999", "1999 .", ". it", "it inhibits", "inhibits tgfb", "tgfb induced", "induced responses", "responses and", "and enhances", "enhances bmp7", "bmp7 induced", "scherner et", ". mutations", "mutations in", "in eng", "eng result", "result in", "in hereditary", "hereditary haemorrhagic", "haemorrhagic telangiectasia", "also known", "known as", "as oslerweberrendu", "oslerweberrendu disease", "while mutations", "in acvrl1", "acvrl1 lead", "lead to", "to hht2", "that they", "they act", "act in", "in a", "a common", "common signalling", "signalling pathway", "mcallister et", "johnson et", "al. 1996", "1996 .", ". bmp2", "bmp2 is", "a dimeric", "dimeric protein", "having two", "two receptor", "receptor binding", "binding motifs.", "motifs. one", "one is", "a high", "high affinity", "affinity binding", "binding site", "site for", "for bmpr1a", "the other", "other is", "a low", "low affinity", "for bmpr2", "kirsch et", "al. 2000", "2000 .", ". in", "of ligand", "ligand stimulation", "small fractions", "fractions of", "present as", "as preexisting", "preexisting homodimers", "homodimers and", "and heterodimers", "heterodimers on", "on the", "the cell", "cell surface.", "surface. ligand", "ligand binding", "binding increases", "increases oligomerization.", "oligomerization. the", "the intracellular", "intracellular domains", "domains of", "receptors have", "have a", "a characteristic", "characteristic gs", "gs domain", "glycine and", "and serine", "serine rich", "rich domain", "located n", "n terminal", "terminal to", "to the", "the serine", "kinase domains.", "domains. type", "receptor kinases", "kinases are", "are constitutively", "constitutively active", "active in", "of ligand.", "ligand. upon", "upon ligand", "kinase phosphorylates", "phosphorylates the", "the gs", "domain of", "a critical", "critical event", "event in", "in signal", "signal transduction", "transduction by", "the serine/threonine", "serine/threonine kinase", ". activation", "activation of", "the tgfbr1", "tgfbr1 receptor", "receptor has", "has been", "been studied", "studied in", "in detail.", "detail. the", "the inactive", "inactive conformation", "conformation is", "is maintained", "maintained by", "by interaction", "interaction between", "between the", "the n", "terminal lobe", "lobe and", "the activation", "activation loop", "loop of", "the kinase", "huse et", ". when", "when the", "domain is", "is phosphorylated", "phosphorylated by", "tgfbr1 kinase", "kinase is", "is converted", "converted to", "to an", "an active", "active conformation.", "conformation. mutations", "mutations of", "of thr", "thr 204", "204 in", "in tgfbr1", "the corresponding", "corresponding gln", "gln in", "in bmp", "receptors lead", "to their", "their constitutive", "constitutive activation.", "activation. the", "the l45", "l45 loop", "kinase domain", "specifically interacts", "interacts with", "with receptor", "receptor regulated", "regulated smads", "r smads", "smads .", ". neurotrophic", "neurotrophic tyrosine", "tyrosine kinase", "type 3", "nt 3", "3 growth", "factor receptor", "directly binds", "binds bmpr2", "interfereing with", "with its", "its interaction", "interaction with", "with bmpr1a", "which inhibits", "inhibits downstream", "downstream signalling", "jin et", ". tyrosine", "tyrosine protein", "kinase transmembrane", "transmembrane receptor", "receptor ror2", "ror2 and", "bmpr1b form", "form a", "a heteromeric", "heteromeric complex", "complex in", "a ligand", "ligand independent", "independent fashion", "fashion that", "that modulatesgdf5", "modulatesgdf5 bmpr1b", "bmpr1b signalling", "signalling by", "by inhibition", "inhibition of", "of smad1/5", "smad1/5 signalling", "sammar et", "al. 2004", "2004 .", ". type", "kinases activated", "activated by", "phosphorylate r", "r smads.", "smads. r", "smads then", "then form", "a complex", "complex with", "with common", "common partner", "partner smad", "co smad", "and translocate", "translocate to", "the nucleus.", "nucleus. the", "the oligomeric", "oligomeric smad", "smad complexes", "complexes regulate", "regulate the", "the transcription", "transcription of", "of target", "target genes", "genes through", "through interaction", "with various", "various transcription", "transcription factors", "factors and", "and transcriptional", "transcriptional coactivators", "coactivators or", "or corepressors.", "corepressors. inhibitory", "inhibitory smads", "i smads", "negatively regulate", "the action", "action of", "of r", "smads and/or", "and/or co", "co smads.", "smads. eight", "eight different", "different smads", "smads have", "identified in", "mammals. smad1", "smad5 and", "and smad8", "smad8 are", "are r", "smads in", "signalling pathways", "bmp specific", "specific r", ". smad2", "smad2 and", "and smad3", "smad3 are", "in tgfb/activin
signalling", "tgfb/activin
signalling pathways.", "bmp receptors", "receptors can", "can phosphorylate", "phosphorylate smad2", "smad2 in", "in certain", "certain types", "of cells", "murakami et", "al. 2009", "2009 .", ". smad1", "are structurally", "structurally highly", "highly similar", "similar to", "to each", "each other.", "other. the", "the functional", "functional differences", "differences between", "between them", "them are", "are largely", "largely unknown.", "unknown. smad4", "smad4 is", "is the", "the only", "only co", "smad in", "in mammals", "by both", "both bmp", "bmp and", "and tgfb/activin", "tgfb/activin signalling", "pathways. smad6", "smad6 and", "and smad7", "smad7 are", "are i", "i smads.", "bone morphogenetic proteins", "proteins bmps", "bmps have", "have many biological", "many biological activities", "biological activities in", "activities in various", "in various tissues", "tissues including", "bone cartilage", "cartilage blood", "vessels heart", "heart kidney", "kidney neurons", "neurons liver", "liver and lung.", "and lung. they", "lung. they are", "they are members", "are members of", "members of the", "of the transforming", "the transforming growth", "transforming growth factor", "growth factor beta", "beta tgfb", "family. they bind", "they bind to", "bind to type", "to type ii", "type ii and", "ii and type", "and type i", "type i serine", "i serine threonine", "serine threonine kinase", "threonine kinase receptors", "receptors which", "which transduce signals", "transduce signals through", "signals through smad", "through smad and", "smad and non", "and non smad", "non smad signalling", "smad signalling pathways.", "signalling pathways. bmp", "pathways. bmp signalling", "bmp signalling is", "signalling is linked", "is linked to", "linked to a", "to a wide", "a wide variety", "wide variety of", "variety of clinical", "of clinical disorders", "disorders including", "including vascular diseases", "diseases skeletal", "skeletal diseases and", "diseases and cancer.", "and cancer. bmps", "cancer. bmps typically", "bmps typically activate", "typically activate bmp", "activate bmp type", "bmp type i", "type i receptors", "i receptors and", "receptors and signal", "and signal via", "signal via smad1", "smad1 5", "5 and 8.", "and 8. they", "8. they can", "they can be", "can be classified", "be classified into", "classified into several", "into several subgroups", "subgroups including", "including the bmp2/4", "the bmp2/4 group", "group the", "the bmp5 8", "bmp5 8 osteogenic", "8 osteogenic protein", "osteogenic protein 1", "1 op1", "op1 group", "the growth and", "growth and differentiation", "and differentiation factor", "factor gdf", "gdf 5", "5 7 group", "7 group and", "group and the", "and the bmp9/10", "the bmp9/10 group.", "bmp9/10 group. most", "group. most of", "most of the", "of the proteins", "the proteins of", "proteins of the", "of the bmp2/4", "bmp2/4 op1", "op1 and bmp9/10", "and bmp9/10 groups", "bmp9/10 groups induce", "groups induce formation", "induce formation of", "formation of bone", "of bone and", "bone and cartilage", "and cartilage tissues", "cartilage tissues in", "tissues in vivo", "vivo while", "while the gdf5", "the gdf5 7", "gdf5 7 group", "7 group induce", "group induce cartilage", "induce cartilage and", "cartilage and tendon", "and tendon like", "like but", "but not bone", "not bone like", "like tissues", "tissues miyazono", "miyazono et al.", "et al. 2010", "al. 2010 .", "2010 . members", ". members of", "of the tgfb", "the tgfb family", "tgfb family bind", "family bind to", "bind to two", "to two types", "two types of", "types of serine", "of serine threonine", "receptors type", "type i and", "i and type", "and type ii", "ii massagu\u00e9", "massagu\u00e9 2012 .", "2012 . bmps", ". bmps can", "bmps can bind", "can bind type", "bind type i", "i receptors in", "receptors in the", "in the absence", "the absence of", "absence of type", "of type ii", "type ii receptors", "receptors but", "but both types", "both types are", "types are required", "are required for", "required for signal", "for signal transduction.", "signal transduction. the", "transduction. the presence", "the presence of", "presence of both", "of both types", "both types dramatically", "types dramatically increases", "dramatically increases binding", "increases binding affinity", "affinity rozenweig", "rozenweig et al.", "et al. 1995", "al. 1995 .", "1995 . the", ". the type", "the type ii", "type ii receptor", "ii receptor kinase", "receptor kinase transphosphorylates", "kinase transphosphorylates the", "transphosphorylates the type", "the type i", "type i receptor", "receptor which", "which transmits specific", "transmits specific intracellular", "specific intracellular signals.", "intracellular signals. type", "signals. type i", "ii receptors share", "receptors share similar", "share similar structural", "similar structural properties", "properties comprised", "comprised of a", "of a relatively", "a relatively short", "relatively short extracellular", "short extracellular domain", "domain a", "a single membrane", "single membrane spanning", "membrane spanning domain", "spanning domain and", "domain and an", "and an intracellular", "an intracellular domain", "intracellular domain containing", "domain containing a", "containing a serine", "a serine threonine", "threonine kinase domain.", "kinase domain. seven", "domain. seven receptors", "receptors collectively", "collectively referred to", "referred to as", "to as the", "as the activin", "the activin receptor", "activin receptor like", "receptor like kinases", "kinases alk", "have been identified", "been identified as", "identified as type", "as type i", "i receptors for", "receptors for the", "for the tgfb", "tgfb family in", "family in mammals.", "in mammals. alks", "mammals. alks are", "alks are classified", "are classified into", "classified into three", "into three groups", "three groups based", "groups based on", "based on their", "on their structure", "their structure and", "structure and function", "function the", "the bmpri group", "group bone", "bone morphogenetic protein", "morphogenetic protein receptor", "protein receptor type", "receptor type 1a", "1a alk3", "alk3 bmpr1a", "bmpr1a and bone", "and bone morphogenetic", "receptor type 1b", "1b alk6", "alk6 bmpr1b", "the alk1 group", "group serine/threonine", "serine/threonine protein kinase", "protein kinase receptor", "kinase receptor r3", "r3 alk1", "alk1 acvrl1", "acvrl1 and activin", "and activin receptor", "activin receptor type", "receptor type 1", "1 alk2", "alk2 acvr1", "and the tbetar1", "the tbetar1 group", "group activin", "1b alk4", "alk4 acvr1b", "and tgf", "tgf beta receptor", "beta receptor type", "1 alk5", "alk5 tgfbr1", "tgfbr1 and activin", "receptor type 1c", "1c alk7", "alk7 acvr1c", "kawabata et al.", "et al. 1998", "al. 1998 .", "1998 . alk1", ". alk1 group", "alk1 group and", "group and bmpri", "and bmpri group", "bmpri group activate", "group activate smad1/5/8", "activate smad1/5/8 and", "smad1/5/8 and transduce", "and transduce similar", "transduce similar intracellular", "similar intracellular signals.", "intracellular signals. the", "signals. the tbetar1", "tbetar1 group activate", "group activate smad2/3.", "activate smad2/3. bmpr1a", "smad2/3. bmpr1a and", "bmpr1a and acvr1", "and acvr1 are", "acvr1 are widely", "are widely expressed.", "widely expressed. bmpr1b", "expressed. bmpr1b shows", "bmpr1b shows a", "shows a more", "a more restricted", "more restricted expression", "restricted expression profile.", "expression profile. acvrl1", "profile. acvrl1 is", "acvrl1 is limited", "is limited to", "limited to endothelial", "to endothelial cells", "endothelial cells and", "cells and a", "and a few", "a few other", "few other cell", "other cell types.", "cell types. the", "types. the binding", "the binding specificities", "binding specificities of", "specificities of bmps", "of bmps to", "bmps to type", "to type i", "i receptors is", "receptors is affected", "is affected by", "affected by the", "by the type", "ii receptors that", "receptors that are", "that are present", "present yu", "yu et al.", "et al. 2005", "al. 2005 .", "2005 . typically", "typically bmp2", "bmp2 and bmp4", "and bmp4 bind", "bmp4 bind to", "bind to bmpr1a", "to bmpr1a and", "bmpr1a and bmpr1b", "bmpr1b ten", "ten dijke et", "dijke et al.", "et al. 1994", "al. 1994 .", "1994 . bmp6", ". bmp6 and", "bmp6 and bmp7", "and bmp7 bind", "bmp7 bind strongly", "bind strongly to", "strongly to acvr1", "to acvr1 and", "acvr1 and weakly", "and weakly to", "weakly to bmpr1b.", "to bmpr1b. growth/differentiation", "bmpr1b. growth/differentiation factor", "growth/differentiation factor 5", "5 bmp14", "bmp14 gdf5", "gdf5 preferentially", "preferentially binds to", "binds to bmpr1b", "bmpr1b but", "but not to", "not to other", "to other type", "other type i", "receptors nishitoh", "nishitoh et al.", "1995 . bmp9", ". bmp9 and", "bmp9 and bmp10", "and bmp10 bind", "bmp10 bind to", "bind to acvrl1", "to acvrl1 and", "acvrl1 and acvrl", "acvrl scharpfenecker", "scharpfenecker et al.", "et al. 2007", "al. 2007 .", "2007 . bmp", ". bmp type", "i receptors are", "receptors are shared", "are shared by", "shared by other", "by other members", "other members of", "the tgfb family.", "tgfb family. three", "family. three receptors", "receptors bone", "receptor type 2", "2 bmpr2", "receptor type 2a", "2a acvr2a", "receptor type 2b", "2b acvr2b", "are the type", "ii receptors for", "receptors for mammalian", "for mammalian bmps.", "mammalian bmps. they", "bmps. they are", "they are widely", "are widely expressed", "widely expressed in", "expressed in various", "in various tissues.", "various tissues. bmpr2", "tissues. bmpr2 is", "bmpr2 is specific", "is specific for", "specific for bmps", "bmps whereas", "whereas acvr2a and", "acvr2a and acvr2b", "and acvr2b are", "acvr2b are shared", "are shared with", "shared with activins", "with activins and", "activins and myostatin.", "and myostatin. bmp", "myostatin. bmp binding", "bmp binding and", "binding and signalling", "and signalling can", "signalling can be", "can be affected", "be affected by", "affected by coreceptors.", "by coreceptors. glycosylphosphatidylinositol", "glycosylphosphatidylinositol gpi", "gpi anchored", "anchored proteins of", "of the repulsive", "the repulsive guidance", "repulsive guidance molecule", "molecule rgm", "rgm family", "family including", "rgma rgmb", "rgmb dragon", "dragon and", "hemojuvelin hfe2", "hfe2 rgmc", "rgmc are", "are coreceptors for", "coreceptors for bmp2", "for bmp2 and", "bmp4 enhancing", "signaling samad", "samad et al.", "2005 babitt", "babitt et al.", "2005 2006", "2006 . they", ". they interact", "they interact with", "interact with bmp", "with bmp type", "type i and/or", "i and/or type", "and/or type ii", "ii receptors and", "receptors and bind", "and bind bmp2", "bind bmp2 and", "bmp4 but", "but not bmp7", "not bmp7 or", "bmp7 or tgfb1.", "or tgfb1. bmp2/4", "tgfb1. bmp2/4 signalling", "bmp2/4 signalling normally", "signalling normally involves", "normally involves bmpr2", "bmpr2 not", "not acvr2a or", "acvr2a or acvr2b.", "or acvr2b. cells", "acvr2b. cells transfected", "cells transfected with", "transfected with rgma", "with rgma use", "rgma use both", "use both bmpr2", "both bmpr2 and", "bmpr2 and acvr2a", "and acvr2a for", "acvr2a for bmp", "for bmp 2/4", "bmp 2/4 signalling", "signalling suggesting", "suggesting that rgma", "that rgma facilitates", "rgma facilitates the", "facilitates the use", "the use of", "use of acvr2a", "of acvr2a by", "acvr2a by bmp2/4", "bmp2/4 xia", "xia et al.", "2007 . endoglin", "endoglin eng", "eng is", "is a transmembrane", "a transmembrane protein", "transmembrane protein expressed", "protein expressed in", "expressed in proliferating", "in proliferating endothelial", "proliferating endothelial cells.", "endothelial cells. it", "cells. it binds", "it binds various", "binds various ligands", "various ligands including", "ligands including tgfb1/3", "tgfb1/3 activin", "activin a and", "a and bmp2/7", "bmp2/7 barbara", "barbara et al.", "et al. 1999", "al. 1999 .", "1999 . it", ". it inhibits", "it inhibits tgfb", "inhibits tgfb induced", "tgfb induced responses", "induced responses and", "responses and enhances", "and enhances bmp7", "enhances bmp7 induced", "bmp7 induced responses", "responses scherner", "scherner et al.", "2007 . mutations", ". mutations in", "mutations in eng", "in eng result", "eng result in", "result in hereditary", "in hereditary haemorrhagic", "hereditary haemorrhagic telangiectasia", "telangiectasia hht1", "also known as", "known as oslerweberrendu", "as oslerweberrendu disease", "disease while", "while mutations in", "mutations in acvrl1", "in acvrl1 lead", "acvrl1 lead to", "lead to hht2", "hht2 suggesting", "suggesting that they", "that they act", "they act in", "act in a", "in a common", "a common signalling", "common signalling pathway", "pathway mcallister", "mcallister et al.", "1994 johnson", "johnson et al.", "et al. 1996", "al. 1996 .", "1996 . bmp2", ". bmp2 is", "bmp2 is a", "is a dimeric", "a dimeric protein", "protein having", "having two receptor", "two receptor binding", "receptor binding motifs.", "binding motifs. one", "motifs. one is", "one is a", "is a high", "a high affinity", "high affinity binding", "affinity binding site", "binding site for", "site for bmpr1a", "bmpr1a the", "the other is", "other is a", "is a low", "a low affinity", "low affinity binding", "site for bmpr2", "bmpr2 kirsch", "kirsch et al.", "et al. 2000", "al. 2000 .", "2000 . in", ". in the", "absence of ligand", "of ligand stimulation", "stimulation small", "small fractions of", "fractions of type", "receptors are present", "are present as", "present as preexisting", "as preexisting homodimers", "preexisting homodimers and", "homodimers and heterodimers", "and heterodimers on", "heterodimers on the", "on the cell", "the cell surface.", "cell surface. ligand", "surface. ligand binding", "ligand binding increases", "binding increases oligomerization.", "increases oligomerization. the", "oligomerization. the intracellular", "the intracellular domains", "intracellular domains of", "domains of type", "of type i", "i receptors have", "receptors have a", "have a characteristic", "a characteristic gs", "characteristic gs domain", "domain glycine", "glycine and serine", "and serine rich", "serine rich domain", "domain located", "located n terminal", "n terminal to", "terminal to the", "to the serine", "the serine threonine", "threonine kinase domains.", "kinase domains. type", "domains. type ii", "ii receptor kinases", "receptor kinases are", "kinases are constitutively", "are constitutively active", "constitutively active in", "active in the", "absence of ligand.", "of ligand. upon", "ligand. upon ligand", "upon ligand binding", "binding the", "receptor kinase phosphorylates", "kinase phosphorylates the", "phosphorylates the gs", "the gs domain", "gs domain of", "domain of the", "of the type", "receptor a", "a critical event", "critical event in", "event in signal", "in signal transduction", "signal transduction by", "transduction by the", "by the serine/threonine", "the serine/threonine kinase", "serine/threonine kinase receptors", "receptors miyazono", "2010 . activation", ". activation of", "activation of the", "of the tgfbr1", "the tgfbr1 receptor", "tgfbr1 receptor has", "receptor has been", "has been studied", "been studied in", "studied in detail.", "in detail. the", "detail. the inactive", "the inactive conformation", "inactive conformation is", "conformation is maintained", "is maintained by", "maintained by interaction", "by interaction between", "interaction between the", "between the gs", "domain the", "the n terminal", "n terminal lobe", "terminal lobe and", "lobe and the", "and the activation", "the activation loop", "activation loop of", "loop of the", "of the kinase", "kinase huse", "huse et al.", "1999 . when", ". when the", "when the gs", "gs domain is", "domain is phosphorylated", "is phosphorylated by", "phosphorylated by the", "kinase the", "the tgfbr1 kinase", "tgfbr1 kinase is", "kinase is converted", "is converted to", "converted to an", "to an active", "an active conformation.", "active conformation. mutations", "conformation. mutations of", "mutations of thr", "of thr 204", "thr 204 in", "204 in tgfbr1", "in tgfbr1 and", "tgfbr1 and the", "and the corresponding", "the corresponding gln", "corresponding gln in", "gln in bmp", "in bmp type", "i receptors lead", "receptors lead to", "lead to their", "to their constitutive", "their constitutive activation.", "constitutive activation. the", "activation. the l45", "the l45 loop", "loop in", "in the kinase", "the kinase domain", "kinase domain of", "receptors specifically", "specifically interacts with", "interacts with receptor", "with receptor regulated", "receptor regulated smads", "smads r", "r smads .", "smads . neurotrophic", ". neurotrophic tyrosine", "neurotrophic tyrosine kinase", "tyrosine kinase receptor", "kinase receptor type", "receptor type 3", "3 nt", "nt 3 growth", "3 growth factor", "growth factor receptor", "receptor trkc", "trkc ntrk3", "ntrk3 directly", "directly binds bmpr2", "bmpr2 interfereing", "interfereing with its", "with its interaction", "its interaction with", "interaction with bmpr1a", "bmpr1a which", "which inhibits downstream", "inhibits downstream signalling", "signalling jin", "jin et al.", "2007 . tyrosine", ". tyrosine protein", "tyrosine protein kinase", "protein kinase transmembrane", "kinase transmembrane receptor", "transmembrane receptor ror2", "receptor ror2 and", "ror2 and bmpr1b", "and bmpr1b form", "bmpr1b form a", "form a heteromeric", "a heteromeric complex", "heteromeric complex in", "complex in a", "in a ligand", "a ligand independent", "ligand independent fashion", "independent fashion that", "fashion that modulatesgdf5", "that modulatesgdf5 bmpr1b", "modulatesgdf5 bmpr1b signalling", "bmpr1b signalling by", "signalling by inhibition", "by inhibition of", "inhibition of smad1/5", "of smad1/5 signalling", "signalling sammar", "sammar et al.", "et al. 2004", "al. 2004 .", "2004 . type", ". type i", "i receptor kinases", "receptor kinases activated", "kinases activated by", "activated by the", "kinases phosphorylate", "phosphorylate r smads.", "r smads. r", "smads. r smads", "r smads then", "smads then form", "then form a", "form a complex", "a complex with", "complex with common", "with common partner", "common partner smad", "smad co", "and translocate to", "translocate to the", "to the nucleus.", "the nucleus. the", "nucleus. the oligomeric", "the oligomeric smad", "oligomeric smad complexes", "smad complexes regulate", "complexes regulate the", "regulate the transcription", "the transcription of", "transcription of target", "of target genes", "target genes through", "genes through interaction", "through interaction with", "interaction with various", "with various transcription", "various transcription factors", "transcription factors and", "factors and transcriptional", "and transcriptional coactivators", "transcriptional coactivators or", "coactivators or corepressors.", "or corepressors. inhibitory", "corepressors. inhibitory smads", "smads i", "smads negatively", "negatively regulate the", "regulate the action", "the action of", "action of r", "of r smads", "r smads and/or", "smads and/or co", "and/or co smads.", "co smads. eight", "smads. eight different", "eight different smads", "different smads have", "smads have been", "been identified in", "identified in mammals.", "in mammals. smad1", "smad1 smad5", "smad5 and smad8", "and smad8 are", "smad8 are r", "are r smads", "r smads in", "smads in bmp", "in bmp signalling", "bmp signalling pathways", "pathways bmp", "bmp specific r", "specific r smads", "smads . smad2", ". smad2 and", "smad2 and smad3", "and smad3 are", "smad3 are r", "smads in tgfb/activin
signalling", "in tgfb/activin
signalling pathways.", "tgfb/activin
signalling pathways. bmp", "pathways. bmp receptors", "bmp receptors can", "receptors can phosphorylate", "can phosphorylate smad2", "phosphorylate smad2 in", "smad2 in certain", "in certain types", "certain types of", "types of cells", "cells murakami", "murakami et al.", "et al. 2009", "al. 2009 .", "2009 . smad1", "smad8 are structurally", "are structurally highly", "structurally highly similar", "highly similar to", "similar to each", "to each other.", "each other. the", "other. the functional", "the functional differences", "functional differences between", "differences between them", "between them are", "them are largely", "are largely unknown.", "largely unknown. smad4", "unknown. smad4 is", "smad4 is the", "is the only", "the only co", "only co smad", "co smad in", "smad in mammals", "mammals shared", "shared by both", "by both bmp", "both bmp and", "bmp and tgfb/activin", "and tgfb/activin signalling", "tgfb/activin signalling pathways.", "signalling pathways. smad6", "pathways. smad6 and", "smad6 and smad7", "and smad7 are", "smad7 are i", "are i smads.", "morphogenetic proteins bmps", "bmps have many", "have many biological activities", "many biological activities in", "biological activities in various", "activities in various tissues", "various tissues including", "tissues including bone", "including bone cartilage", "cartilage blood vessels", "blood vessels heart", "neurons liver and", "liver and lung. they", "and lung. they are", "lung. they are members", "they are members of", "are members of the", "members of the transforming", "of the transforming growth", "the transforming growth factor", "transforming growth factor beta", "factor beta tgfb", "tgfb family. they", "family. they bind to", "they bind to type", "bind to type ii", "to type ii and", "type ii and type", "ii and type i", "and type i serine", "type i serine threonine", "i serine threonine kinase", "serine threonine kinase receptors", "kinase receptors which", "receptors which transduce", "which transduce signals through", "transduce signals through smad", "signals through smad and", "through smad and non", "smad and non smad", "and non smad signalling", "non smad signalling pathways.", "smad signalling pathways. bmp", "signalling pathways. bmp signalling", "pathways. bmp signalling is", "bmp signalling is linked", "signalling is linked to", "is linked to a", "linked to a wide", "to a wide variety", "a wide variety of", "wide variety of clinical", "variety of clinical disorders", "clinical disorders including", "disorders including vascular", "vascular diseases skeletal", "diseases skeletal diseases", "skeletal diseases and cancer.", "diseases and cancer. bmps", "and cancer. bmps typically", "cancer. bmps typically activate", "bmps typically activate bmp", "typically activate bmp type", "activate bmp type i", "bmp type i receptors", "type i receptors and", "i receptors and signal", "receptors and signal via", "and signal via smad1", "via smad1 5", "smad1 5 and", "5 and 8. they", "and 8. they can", "8. they can be", "they can be classified", "can be classified into", "be classified into several", "classified into several subgroups", "several subgroups including", "subgroups including the", "including the bmp2/4 group", "bmp2/4 group the", "group the bmp5", "the bmp5 8 osteogenic", "bmp5 8 osteogenic protein", "8 osteogenic protein 1", "protein 1 op1", "group the growth", "the growth and differentiation", "growth and differentiation factor", "differentiation factor gdf", "gdf 5 7", "5 7 group and", "7 group and the", "group and the bmp9/10", "and the bmp9/10 group.", "the bmp9/10 group. most", "bmp9/10 group. most of", "group. most of the", "most of the proteins", "of the proteins of", "the proteins of the", "proteins of the bmp2/4", "the bmp2/4 op1", "bmp2/4 op1 and", "op1 and bmp9/10 groups", "and bmp9/10 groups induce", "bmp9/10 groups induce formation", "groups induce formation of", "induce formation of bone", "formation of bone and", "of bone and cartilage", "bone and cartilage tissues", "and cartilage tissues in", "cartilage tissues in vivo", "in vivo while", "vivo while the", "while the gdf5 7", "the gdf5 7 group", "gdf5 7 group induce", "7 group induce cartilage", "group induce cartilage and", "induce cartilage and tendon", "cartilage and tendon like", "tendon like but", "like but not", "but not bone like", "bone like tissues", "tissues miyazono et", "miyazono et al. 2010", "et al. 2010 .", "al. 2010 . members", "2010 . members of", ". members of the", "members of the tgfb", "of the tgfb family", "the tgfb family bind", "tgfb family bind to", "family bind to two", "bind to two types", "to two types of", "two types of serine", "types of serine threonine", "of serine threonine kinase", "kinase receptors type", "receptors type i", "type i and type", "i and type ii", "type ii massagu\u00e9", "ii massagu\u00e9 2012", "massagu\u00e9 2012 . bmps", "2012 . bmps can", ". bmps can bind", "bmps can bind type", "can bind type i", "bind type i receptors", "type i receptors in", "i receptors in the", "receptors in the absence", "in the absence of", "the absence of type", "absence of type ii", "of type ii receptors", "ii receptors but", "receptors but both", "but both types are", "both types are required", "types are required for", "are required for signal", "required for signal transduction.", "for signal transduction. the", "signal transduction. the presence", "transduction. the presence of", "the presence of both", "presence of both types", "of both types dramatically", "both types dramatically increases", "types dramatically increases binding", "dramatically increases binding affinity", "binding affinity rozenweig", "affinity rozenweig et", "rozenweig et al. 1995", "et al. 1995 .", "al. 1995 . the", "1995 . the type", ". the type ii", "the type ii receptor", "type ii receptor kinase", "ii receptor kinase transphosphorylates", "receptor kinase transphosphorylates the", "kinase transphosphorylates the type", "transphosphorylates the type i", "the type i receptor", "i receptor which", "receptor which transmits", "which transmits specific intracellular", "transmits specific intracellular signals.", "specific intracellular signals. type", "intracellular signals. type i", "signals. type i and", "and type ii receptors", "type ii receptors share", "ii receptors share similar", "receptors share similar structural", "share similar structural properties", "structural properties comprised", "properties comprised of", "comprised of a relatively", "of a relatively short", "a relatively short extracellular", "relatively short extracellular domain", "extracellular domain a", "domain a single", "a single membrane spanning", "single membrane spanning domain", "membrane spanning domain and", "spanning domain and an", "domain and an intracellular", "and an intracellular domain", "an intracellular domain containing", "intracellular domain containing a", "domain containing a serine", "containing a serine threonine", "a serine threonine kinase", "serine threonine kinase domain.", "threonine kinase domain. seven", "kinase domain. seven receptors", "seven receptors collectively", "receptors collectively referred", "collectively referred to as", "referred to as the", "to as the activin", "as the activin receptor", "the activin receptor like", "activin receptor like kinases", "like kinases alk", "alk have", "have been identified as", "been identified as type", "identified as type i", "as type i receptors", "type i receptors for", "i receptors for the", "receptors for the tgfb", "for the tgfb family", "the tgfb family in", "tgfb family in mammals.", "family in mammals. alks", "in mammals. alks are", "mammals. alks are classified", "alks are classified into", "are classified into three", "classified into three groups", "into three groups based", "three groups based on", "groups based on their", "based on their structure", "on their structure and", "their structure and function", "and function the", "function the bmpri", "bmpri group bone", "group bone morphogenetic", "bone morphogenetic protein receptor", "morphogenetic protein receptor type", "protein receptor type 1a", "type 1a alk3", "alk3 bmpr1a and", "bmpr1a and bone morphogenetic", "and bone morphogenetic protein", "protein receptor type 1b", "type 1b alk6", "bmpr1b the", "alk1 group serine/threonine", "group serine/threonine protein", "serine/threonine protein kinase receptor", "protein kinase receptor r3", "receptor r3 alk1", "alk1 acvrl1 and", "acvrl1 and activin receptor", "and activin receptor type", "activin receptor type 1", "type 1 alk2", "acvr1 and the", "and the tbetar1 group", "tbetar1 group activin", "group activin receptor", "activin receptor type 1b", "type 1b alk4", "alk4 acvr1b and", "acvr1b and tgf", "and tgf beta", "tgf beta receptor type", "beta receptor type 1", "type 1 alk5", "alk5 tgfbr1 and", "tgfbr1 and activin receptor", "activin receptor type 1c", "type 1c alk7", "acvr1c kawabata", "kawabata et al. 1998", "et al. 1998 .", "al. 1998 . alk1", "1998 . alk1 group", ". alk1 group and", "alk1 group and bmpri", "group and bmpri group", "and bmpri group activate", "bmpri group activate smad1/5/8", "group activate smad1/5/8 and", "activate smad1/5/8 and transduce", "smad1/5/8 and transduce similar", "and transduce similar intracellular", "transduce similar intracellular signals.", "similar intracellular signals. the", "intracellular signals. the tbetar1", "signals. the tbetar1 group", "the tbetar1 group activate", "tbetar1 group activate smad2/3.", "group activate smad2/3. bmpr1a", "activate smad2/3. bmpr1a and", "smad2/3. bmpr1a and acvr1", "bmpr1a and acvr1 are", "and acvr1 are widely", "acvr1 are widely expressed.", "are widely expressed. bmpr1b", "widely expressed. bmpr1b shows", "expressed. bmpr1b shows a", "bmpr1b shows a more", "shows a more restricted", "a more restricted expression", "more restricted expression profile.", "restricted expression profile. acvrl1", "expression profile. acvrl1 is", "profile. acvrl1 is limited", "acvrl1 is limited to", "is limited to endothelial", "limited to endothelial cells", "to endothelial cells and", "endothelial cells and a", "cells and a few", "and a few other", "a few other cell", "few other cell types.", "other cell types. the", "cell types. the binding", "types. the binding specificities", "the binding specificities of", "binding specificities of bmps", "specificities of bmps to", "of bmps to type", "bmps to type i", "to type i receptors", "type i receptors is", "i receptors is affected", "receptors is affected by", "is affected by the", "affected by the type", "by the type ii", "the type ii receptors", "type ii receptors that", "ii receptors that are", "receptors that are present", "are present yu", "present yu et", "yu et al. 2005", "et al. 2005 .", "al. 2005 . typically", ". typically bmp2", "typically bmp2 and", "bmp2 and bmp4 bind", "and bmp4 bind to", "bmp4 bind to bmpr1a", "bind to bmpr1a and", "to bmpr1a and bmpr1b", "and bmpr1b ten", "bmpr1b ten dijke", "ten dijke et al.", "dijke et al. 1994", "et al. 1994 .", "al. 1994 . bmp6", "1994 . bmp6 and", ". bmp6 and bmp7", "bmp6 and bmp7 bind", "and bmp7 bind strongly", "bmp7 bind strongly to", "bind strongly to acvr1", "strongly to acvr1 and", "to acvr1 and weakly", "acvr1 and weakly to", "and weakly to bmpr1b.", "weakly to bmpr1b. growth/differentiation", "to bmpr1b. growth/differentiation factor", "bmpr1b. growth/differentiation factor 5", "factor 5 bmp14", "gdf5 preferentially binds", "preferentially binds to bmpr1b", "to bmpr1b but", "bmpr1b but not", "but not to other", "not to other type", "to other type i", "other type i receptors", "i receptors nishitoh", "receptors nishitoh et", "nishitoh et al. 1995", "al. 1995 . bmp9", "1995 . bmp9 and", ". bmp9 and bmp10", "bmp9 and bmp10 bind", "and bmp10 bind to", "bmp10 bind to acvrl1", "bind to acvrl1 and", "to acvrl1 and acvrl", "and acvrl scharpfenecker", "acvrl scharpfenecker et", "scharpfenecker et al. 2007", "et al. 2007 .", "al. 2007 . bmp", "2007 . bmp type", ". bmp type i", "type i receptors are", "i receptors are shared", "receptors are shared by", "are shared by other", "shared by other members", "by other members of", "other members of the", "of the tgfb family.", "the tgfb family. three", "tgfb family. three receptors", "three receptors bone", "receptors bone morphogenetic", "protein receptor type 2", "type 2 bmpr2", "bmpr2 activin", "activin receptor type 2a", "type 2a acvr2a", "acvr2a and activin", "activin receptor type 2b", "type 2b acvr2b", "acvr2b are the", "are the type ii", "type ii receptors for", "ii receptors for mammalian", "receptors for mammalian bmps.", "for mammalian bmps. they", "mammalian bmps. they are", "bmps. they are widely", "they are widely expressed", "are widely expressed in", "widely expressed in various", "expressed in various tissues.", "in various tissues. bmpr2", "various tissues. bmpr2 is", "tissues. bmpr2 is specific", "bmpr2 is specific for", "is specific for bmps", "for bmps whereas", "bmps whereas acvr2a", "whereas acvr2a and acvr2b", "acvr2a and acvr2b are", "and acvr2b are shared", "acvr2b are shared with", "are shared with activins", "shared with activins and", "with activins and myostatin.", "activins and myostatin. bmp", "and myostatin. bmp binding", "myostatin. bmp binding and", "bmp binding and signalling", "binding and signalling can", "and signalling can be", "signalling can be affected", "can be affected by", "be affected by coreceptors.", "affected by coreceptors. glycosylphosphatidylinositol", "coreceptors. glycosylphosphatidylinositol gpi", "gpi anchored proteins", "anchored proteins of the", "proteins of the repulsive", "of the repulsive guidance", "the repulsive guidance molecule", "guidance molecule rgm", "family including rgma", "including rgma rgmb", "dragon and hemojuvelin", "and hemojuvelin hfe2", "rgmc are coreceptors", "are coreceptors for bmp2", "coreceptors for bmp2 and", "for bmp2 and bmp4", "and bmp4 enhancing", "bmp4 enhancing signaling", "enhancing signaling samad", "signaling samad et", "samad et al. 2005", "al. 2005 babitt", "2005 babitt et", "babitt et al. 2005", "al. 2005 2006", "2005 2006 .", "2006 . they interact", ". they interact with", "they interact with bmp", "interact with bmp type", "with bmp type i", "bmp type i and/or", "type i and/or type", "i and/or type ii", "and/or type ii receptors", "type ii receptors and", "ii receptors and bind", "receptors and bind bmp2", "and bind bmp2 and", "bind bmp2 and bmp4", "and bmp4 but", "bmp4 but not", "but not bmp7 or", "not bmp7 or tgfb1.", "bmp7 or tgfb1. bmp2/4", "or tgfb1. bmp2/4 signalling", "tgfb1. bmp2/4 signalling normally", "bmp2/4 signalling normally involves", "signalling normally involves bmpr2", "involves bmpr2 not", "bmpr2 not acvr2a", "not acvr2a or acvr2b.", "acvr2a or acvr2b. cells", "or acvr2b. cells transfected", "acvr2b. cells transfected with", "cells transfected with rgma", "transfected with rgma use", "with rgma use both", "rgma use both bmpr2", "use both bmpr2 and", "both bmpr2 and acvr2a", "bmpr2 and acvr2a for", "and acvr2a for bmp", "acvr2a for bmp 2/4", "for bmp 2/4 signalling", "2/4 signalling suggesting", "signalling suggesting that", "suggesting that rgma facilitates", "that rgma facilitates the", "rgma facilitates the use", "facilitates the use of", "the use of acvr2a", "use of acvr2a by", "of acvr2a by bmp2/4", "by bmp2/4 xia", "bmp2/4 xia et", "xia et al. 2007", "al. 2007 . endoglin", ". endoglin eng", "eng is a", "is a transmembrane protein", "a transmembrane protein expressed", "transmembrane protein expressed in", "protein expressed in proliferating", "expressed in proliferating endothelial", "in proliferating endothelial cells.", "proliferating endothelial cells. it", "endothelial cells. it binds", "cells. it binds various", "it binds various ligands", "binds various ligands including", "various ligands including tgfb1/3", "including tgfb1/3 activin", "tgfb1/3 activin a", "activin a and bmp2/7", "and bmp2/7 barbara", "bmp2/7 barbara et", "barbara et al. 1999", "et al. 1999 .", "al. 1999 . it", "1999 . it inhibits", ". it inhibits tgfb", "it inhibits tgfb induced", "inhibits tgfb induced responses", "tgfb induced responses and", "induced responses and enhances", "responses and enhances bmp7", "and enhances bmp7 induced", "enhances bmp7 induced responses", "induced responses scherner", "responses scherner et", "scherner et al. 2007", "al. 2007 . mutations", "2007 . mutations in", ". mutations in eng", "mutations in eng result", "in eng result in", "eng result in hereditary", "result in hereditary haemorrhagic", "in hereditary haemorrhagic telangiectasia", "haemorrhagic telangiectasia hht1", "hht1 also", "also known as oslerweberrendu", "known as oslerweberrendu disease", "oslerweberrendu disease while", "disease while mutations", "while mutations in acvrl1", "mutations in acvrl1 lead", "in acvrl1 lead to", "acvrl1 lead to hht2", "to hht2 suggesting", "hht2 suggesting that", "suggesting that they act", "that they act in", "they act in a", "act in a common", "in a common signalling", "a common signalling pathway", "signalling pathway mcallister", "pathway mcallister et", "mcallister et al. 1994", "al. 1994 johnson", "1994 johnson et", "johnson et al. 1996", "et al. 1996 .", "al. 1996 . bmp2", "1996 . bmp2 is", ". bmp2 is a", "bmp2 is a dimeric", "is a dimeric protein", "dimeric protein having", "protein having two", "having two receptor binding", "two receptor binding motifs.", "receptor binding motifs. one", "binding motifs. one is", "motifs. one is a", "one is a high", "is a high affinity", "a high affinity binding", "high affinity binding site", "affinity binding site for", "binding site for bmpr1a", "for bmpr1a the", "bmpr1a the other", "the other is a", "other is a low", "is a low affinity", "a low affinity binding", "low affinity binding site", "binding site for bmpr2", "for bmpr2 kirsch", "bmpr2 kirsch et", "kirsch et al. 2000", "et al. 2000 .", "al. 2000 . in", "2000 . in the", ". in the absence", "the absence of ligand", "absence of ligand stimulation", "ligand stimulation small", "stimulation small fractions", "small fractions of type", "fractions of type ii", "of type ii and", "and type i receptors", "i receptors are present", "receptors are present as", "are present as preexisting", "present as preexisting homodimers", "as preexisting homodimers and", "preexisting homodimers and heterodimers", "homodimers and heterodimers on", "and heterodimers on the", "heterodimers on the cell", "on the cell surface.", "the cell surface. ligand", "cell surface. ligand binding", "surface. ligand binding increases", "ligand binding increases oligomerization.", "binding increases oligomerization. the", "increases oligomerization. the intracellular", "oligomerization. the intracellular domains", "the intracellular domains of", "intracellular domains of type", "domains of type i", "of type i receptors", "type i receptors have", "i receptors have a", "receptors have a characteristic", "have a characteristic gs", "a characteristic gs domain", "gs domain glycine", "domain glycine and", "glycine and serine rich", "and serine rich domain", "rich domain located", "domain located n", "located n terminal to", "n terminal to the", "terminal to the serine", "to the serine threonine", "the serine threonine kinase", "serine threonine kinase domains.", "threonine kinase domains. type", "kinase domains. type ii", "domains. type ii receptor", "type ii receptor kinases", "ii receptor kinases are", "receptor kinases are constitutively", "kinases are constitutively active", "are constitutively active in", "constitutively active in the", "active in the absence", "the absence of ligand.", "absence of ligand. upon", "of ligand. upon ligand", "ligand. upon ligand binding", "ligand binding the", "binding the type", "ii receptor kinase phosphorylates", "receptor kinase phosphorylates the", "kinase phosphorylates the gs", "phosphorylates the gs domain", "the gs domain of", "gs domain of the", "domain of the type", "of the type i", "i receptor a", "receptor a critical", "a critical event in", "critical event in signal", "event in signal transduction", "in signal transduction by", "signal transduction by the", "transduction by the serine/threonine", "by the serine/threonine kinase", "the serine/threonine kinase receptors", "kinase receptors miyazono", "receptors miyazono et", "al. 2010 . activation", "2010 . activation of", ". activation of the", "activation of the tgfbr1", "of the tgfbr1 receptor", "the tgfbr1 receptor has", "tgfbr1 receptor has been", "receptor has been studied", "has been studied in", "been studied in detail.", "studied in detail. the", "in detail. the inactive", "detail. the inactive conformation", "the inactive conformation is", "inactive conformation is maintained", "conformation is maintained by", "is maintained by interaction", "maintained by interaction between", "by interaction between the", "interaction between the gs", "between the gs domain", "gs domain the", "domain the n", "the n terminal lobe", "n terminal lobe and", "terminal lobe and the", "lobe and the activation", "and the activation loop", "the activation loop of", "activation loop of the", "loop of the kinase", "the kinase huse", "kinase huse et", "huse et al. 1999", "al. 1999 . when", "1999 . when the", ". when the gs", "when the gs domain", "the gs domain is", "gs domain is phosphorylated", "domain is phosphorylated by", "is phosphorylated by the", "phosphorylated by the type", "receptor kinase the", "kinase the tgfbr1", "the tgfbr1 kinase is", "tgfbr1 kinase is converted", "kinase is converted to", "is converted to an", "converted to an active", "to an active conformation.", "an active conformation. mutations", "active conformation. mutations of", "conformation. mutations of thr", "mutations of thr 204", "of thr 204 in", "thr 204 in tgfbr1", "204 in tgfbr1 and", "in tgfbr1 and the", "tgfbr1 and the corresponding", "and the corresponding gln", "the corresponding gln in", "corresponding gln in bmp", "gln in bmp type", "in bmp type i", "type i receptors lead", "i receptors lead to", "receptors lead to their", "lead to their constitutive", "to their constitutive activation.", "their constitutive activation. the", "constitutive activation. the l45", "activation. the l45 loop", "l45 loop in", "loop in the", "in the kinase domain", "the kinase domain of", "domain of type", "i receptors specifically", "receptors specifically interacts", "specifically interacts with receptor", "interacts with receptor regulated", "with receptor regulated smads", "regulated smads r", "smads r smads", "r smads . neurotrophic", "smads . neurotrophic tyrosine", ". neurotrophic tyrosine kinase", "neurotrophic tyrosine kinase receptor", "tyrosine kinase receptor type", "kinase receptor type 3", "type 3 nt", "3 nt 3", "nt 3 growth factor", "3 growth factor receptor", "factor receptor trkc", "ntrk3 directly binds", "binds bmpr2 interfereing", "bmpr2 interfereing with", "interfereing with its interaction", "with its interaction with", "its interaction with bmpr1a", "with bmpr1a which", "bmpr1a which inhibits", "which inhibits downstream signalling", "downstream signalling jin", "signalling jin et", "jin et al. 2007", "al. 2007 . tyrosine", "2007 . tyrosine protein", ". tyrosine protein kinase", "tyrosine protein kinase transmembrane", "protein kinase transmembrane receptor", "kinase transmembrane receptor ror2", "transmembrane receptor ror2 and", "receptor ror2 and bmpr1b", "ror2 and bmpr1b form", "and bmpr1b form a", "bmpr1b form a heteromeric", "form a heteromeric complex", "a heteromeric complex in", "heteromeric complex in a", "complex in a ligand", "in a ligand independent", "a ligand independent fashion", "ligand independent fashion that", "independent fashion that modulatesgdf5", "fashion that modulatesgdf5 bmpr1b", "that modulatesgdf5 bmpr1b signalling", "modulatesgdf5 bmpr1b signalling by", "bmpr1b signalling by inhibition", "signalling by inhibition of", "by inhibition of smad1/5", "inhibition of smad1/5 signalling", "smad1/5 signalling sammar", "signalling sammar et", "sammar et al. 2004", "et al. 2004 .", "al. 2004 . type", "2004 . type i", ". type i receptor", "type i receptor kinases", "i receptor kinases activated", "receptor kinases activated by", "kinases activated by the", "activated by the type", "receptor kinases phosphorylate", "kinases phosphorylate r", "phosphorylate r smads. r", "r smads. r smads", "smads. r smads then", "r smads then form", "smads then form a", "then form a complex", "form a complex with", "a complex with common", "complex with common partner", "with common partner smad", "partner smad co", "smad co smad", "co smad and", "smad and translocate", "and translocate to the", "translocate to the nucleus.", "to the nucleus. the", "the nucleus. the oligomeric", "nucleus. the oligomeric smad", "the oligomeric smad complexes", "oligomeric smad complexes regulate", "smad complexes regulate the", "complexes regulate the transcription", "regulate the transcription of", "the transcription of target", "transcription of target genes", "of target genes through", "target genes through interaction", "genes through interaction with", "through interaction with various", "interaction with various transcription", "with various transcription factors", "various transcription factors and", "transcription factors and transcriptional", "factors and transcriptional coactivators", "and transcriptional coactivators or", "transcriptional coactivators or corepressors.", "coactivators or corepressors. inhibitory", "or corepressors. inhibitory smads", "inhibitory smads i", "smads i smads", "i smads negatively", "smads negatively regulate", "negatively regulate the action", "regulate the action of", "the action of r", "action of r smads", "of r smads and/or", "r smads and/or co", "smads and/or co smads.", "and/or co smads. eight", "co smads. eight different", "smads. eight different smads", "eight different smads have", "different smads have been", "smads have been identified", "have been identified in", "been identified in mammals.", "identified in mammals. smad1", "mammals. smad1 smad5", "smad1 smad5 and", "smad5 and smad8 are", "and smad8 are r", "smad8 are r smads", "are r smads in", "r smads in bmp", "smads in bmp signalling", "in bmp signalling pathways", "signalling pathways bmp", "pathways bmp specific", "bmp specific r smads", "specific r smads .", "r smads . smad2", "smads . smad2 and", ". smad2 and smad3", "smad2 and smad3 are", "and smad3 are r", "smad3 are r smads", "r smads in tgfb/activin
signalling", "smads in tgfb/activin
signalling pathways.", "in tgfb/activin
signalling pathways. bmp", "tgfb/activin
signalling pathways. bmp receptors", "pathways. bmp receptors can", "bmp receptors can phosphorylate", "receptors can phosphorylate smad2", "can phosphorylate smad2 in", "phosphorylate smad2 in certain", "smad2 in certain types", "in certain types of", "certain types of cells", "of cells murakami", "cells murakami et", "murakami et al. 2009", "et al. 2009 .", "al. 2009 . smad1", ". smad1 smad5", "and smad8 are structurally", "smad8 are structurally highly", "are structurally highly similar", "structurally highly similar to", "highly similar to each", "similar to each other.", "to each other. the", "each other. the functional", "other. the functional differences", "the functional differences between", "functional differences between them", "differences between them are", "between them are largely", "them are largely unknown.", "are largely unknown. smad4", "largely unknown. smad4 is", "unknown. smad4 is the", "smad4 is the only", "is the only co", "the only co smad", "only co smad in", "co smad in mammals", "in mammals shared", "mammals shared by", "shared by both bmp", "by both bmp and", "both bmp and tgfb/activin", "bmp and tgfb/activin signalling", "and tgfb/activin signalling pathways.", "tgfb/activin signalling pathways. smad6", "signalling pathways. smad6 and", "pathways. smad6 and smad7", "smad6 and smad7 are", "and smad7 are i", "smad7 are i smads.", "bone morphogenetic proteins bmps", "proteins bmps have", "bmps have many biological", "have many biological activities in", "many biological activities in various", "biological activities in various tissues", "in various tissues including", "various tissues including bone", "bone cartilage blood", "vessels heart kidney", "heart kidney neurons", "kidney neurons liver", "neurons liver and lung.", "liver and lung. they are", "and lung. they are members", "lung. they are members of", "they are members of the", "are members of the transforming", "members of the transforming growth", "of the transforming growth factor", "the transforming growth factor beta", "growth factor beta tgfb", "beta tgfb family.", "tgfb family. they bind", "family. they bind to type", "they bind to type ii", "bind to type ii and", "to type ii and type", "type ii and type i", "ii and type i serine", "and type i serine threonine", "type i serine threonine kinase", "i serine threonine kinase receptors", "threonine kinase receptors which", "kinase receptors which transduce", "receptors which transduce signals", "which transduce signals through smad", "transduce signals through smad and", "signals through smad and non", "through smad and non smad", "smad and non smad signalling", "and non smad signalling pathways.", "non smad signalling pathways. bmp", "smad signalling pathways. bmp signalling", "signalling pathways. bmp signalling is", "pathways. bmp signalling is linked", "bmp signalling is linked to", "signalling is linked to a", "is linked to a wide", "linked to a wide variety", "to a wide variety of", "a wide variety of clinical", "wide variety of clinical disorders", "of clinical disorders including", "clinical disorders including vascular", "disorders including vascular diseases", "including vascular diseases skeletal", "vascular diseases skeletal diseases", "diseases skeletal diseases and", "skeletal diseases and cancer. bmps", "diseases and cancer. bmps typically", "and cancer. bmps typically activate", "cancer. bmps typically activate bmp", "bmps typically activate bmp type", "typically activate bmp type i", "activate bmp type i receptors", "bmp type i receptors and", "type i receptors and signal", "i receptors and signal via", "receptors and signal via smad1", "signal via smad1 5", "via smad1 5 and", "smad1 5 and 8.", "5 and 8. they can", "and 8. they can be", "8. they can be classified", "they can be classified into", "can be classified into several", "be classified into several subgroups", "into several subgroups including", "several subgroups including the", "subgroups including the bmp2/4", "the bmp2/4 group the", "bmp2/4 group the bmp5", "group the bmp5 8", "the bmp5 8 osteogenic protein", "bmp5 8 osteogenic protein 1", "osteogenic protein 1 op1", "1 op1 group", "op1 group the", "group the growth and", "the growth and differentiation factor", "and differentiation factor gdf", "factor gdf 5", "gdf 5 7 group", "5 7 group and the", "7 group and the bmp9/10", "group and the bmp9/10 group.", "and the bmp9/10 group. most", "the bmp9/10 group. most of", "bmp9/10 group. most of the", "group. most of the proteins", "most of the proteins of", "of the proteins of the", "the proteins of the bmp2/4", "of the bmp2/4 op1", "the bmp2/4 op1 and", "bmp2/4 op1 and bmp9/10", "op1 and bmp9/10 groups induce", "and bmp9/10 groups induce formation", "bmp9/10 groups induce formation of", "groups induce formation of bone", "induce formation of bone and", "formation of bone and cartilage", "of bone and cartilage tissues", "bone and cartilage tissues in", "and cartilage tissues in vivo", "tissues in vivo while", "in vivo while the", "vivo while the gdf5", "while the gdf5 7 group", "the gdf5 7 group induce", "gdf5 7 group induce cartilage", "7 group induce cartilage and", "group induce cartilage and tendon", "induce cartilage and tendon like", "and tendon like but", "tendon like but not", "like but not bone", "not bone like tissues", "like tissues miyazono", "tissues miyazono et al.", "miyazono et al. 2010 .", "et al. 2010 . members", "al. 2010 . members of", "2010 . members of the", ". members of the tgfb", "members of the tgfb family", "of the tgfb family bind", "the tgfb family bind to", "tgfb family bind to two", "family bind to two types", "bind to two types of", "to two types of serine", "two types of serine threonine", "types of serine threonine kinase", "of serine threonine kinase receptors", "threonine kinase receptors type", "kinase receptors type i", "receptors type i and", "type i and type ii", "and type ii massagu\u00e9", "type ii massagu\u00e9 2012", "ii massagu\u00e9 2012 .", "massagu\u00e9 2012 . bmps can", "2012 . bmps can bind", ". bmps can bind type", "bmps can bind type i", "can bind type i receptors", "bind type i receptors in", "type i receptors in the", "i receptors in the absence", "receptors in the absence of", "in the absence of type", "the absence of type ii", "absence of type ii receptors", "type ii receptors but", "ii receptors but both", "receptors but both types", "but both types are required", "both types are required for", "types are required for signal", "are required for signal transduction.", "required for signal transduction. the", "for signal transduction. the presence", "signal transduction. the presence of", "transduction. the presence of both", "the presence of both types", "presence of both types dramatically", "of both types dramatically increases", "both types dramatically increases binding", "types dramatically increases binding affinity", "increases binding affinity rozenweig", "binding affinity rozenweig et", "affinity rozenweig et al.", "rozenweig et al. 1995 .", "et al. 1995 . the", "al. 1995 . the type", "1995 . the type ii", ". the type ii receptor", "the type ii receptor kinase", "type ii receptor kinase transphosphorylates", "ii receptor kinase transphosphorylates the", "receptor kinase transphosphorylates the type", "kinase transphosphorylates the type i", "transphosphorylates the type i receptor", "type i receptor which", "i receptor which transmits", "receptor which transmits specific", "which transmits specific intracellular signals.", "transmits specific intracellular signals. type", "specific intracellular signals. type i", "intracellular signals. type i and", "signals. type i and type", "i and type ii receptors", "and type ii receptors share", "type ii receptors share similar", "ii receptors share similar structural", "receptors share similar structural properties", "similar structural properties comprised", "structural properties comprised of", "properties comprised of a", "comprised of a relatively short", "of a relatively short extracellular", "a relatively short extracellular domain", "short extracellular domain a", "extracellular domain a single", "domain a single membrane", "a single membrane spanning domain", "single membrane spanning domain and", "membrane spanning domain and an", "spanning domain and an intracellular", "domain and an intracellular domain", "and an intracellular domain containing", "an intracellular domain containing a", "intracellular domain containing a serine", "domain containing a serine threonine", "containing a serine threonine kinase", "a serine threonine kinase domain.", "serine threonine kinase domain. seven", "threonine kinase domain. seven receptors", "domain. seven receptors collectively", "seven receptors collectively referred", "receptors collectively referred to", "collectively referred to as the", "referred to as the activin", "to as the activin receptor", "as the activin receptor like", "the activin receptor like kinases", "receptor like kinases alk", "alk have been", "have been identified as type", "been identified as type i", "identified as type i receptors", "as type i receptors for", "type i receptors for the", "i receptors for the tgfb", "receptors for the tgfb family", "for the tgfb family in", "the tgfb family in mammals.", "tgfb family in mammals. alks", "family in mammals. alks are", "in mammals. alks are classified", "mammals. alks are classified into", "alks are classified into three", "are classified into three groups", "classified into three groups based", "into three groups based on", "three groups based on their", "groups based on their structure", "based on their structure and", "on their structure and function", "structure and function the", "and function the bmpri", "function the bmpri group", "the bmpri group bone", "bmpri group bone morphogenetic", "group bone morphogenetic protein", "bone morphogenetic protein receptor type", "morphogenetic protein receptor type 1a", "receptor type 1a alk3", "1a alk3 bmpr1a", "alk3 bmpr1a and bone", "bmpr1a and bone morphogenetic protein", "and bone morphogenetic protein receptor", "morphogenetic protein receptor type 1b", "receptor type 1b alk6", "1b alk6 bmpr1b", "bmpr1b the alk1", "the alk1 group serine/threonine", "alk1 group serine/threonine protein", "group serine/threonine protein kinase", "serine/threonine protein kinase receptor r3", "kinase receptor r3 alk1", "r3 alk1 acvrl1", "alk1 acvrl1 and activin", "acvrl1 and activin receptor type", "and activin receptor type 1", "receptor type 1 alk2", "1 alk2 acvr1", "alk2 acvr1 and", "acvr1 and the tbetar1", "the tbetar1 group activin", "tbetar1 group activin receptor", "group activin receptor type", "receptor type 1b alk4", "1b alk4 acvr1b", "acvr1b and tgf beta", "and tgf beta receptor", "tgf beta receptor type 1", "receptor type 1 alk5", "1 alk5 tgfbr1", "alk5 tgfbr1 and activin", "tgfbr1 and activin receptor type", "and activin receptor type 1c", "receptor type 1c alk7", "1c alk7 acvr1c", "acvr1c kawabata et", "kawabata et al. 1998 .", "et al. 1998 . alk1", "al. 1998 . alk1 group", "1998 . alk1 group and", ". alk1 group and bmpri", "alk1 group and bmpri group", "group and bmpri group activate", "and bmpri group activate smad1/5/8", "bmpri group activate smad1/5/8 and", "group activate smad1/5/8 and transduce", "activate smad1/5/8 and transduce similar", "smad1/5/8 and transduce similar intracellular", "and transduce similar intracellular signals.", "transduce similar intracellular signals. the", "similar intracellular signals. the tbetar1", "intracellular signals. the tbetar1 group", "signals. the tbetar1 group activate", "the tbetar1 group activate smad2/3.", "tbetar1 group activate smad2/3. bmpr1a", "group activate smad2/3. bmpr1a and", "activate smad2/3. bmpr1a and acvr1", "smad2/3. bmpr1a and acvr1 are", "bmpr1a and acvr1 are widely", "and acvr1 are widely expressed.", "acvr1 are widely expressed. bmpr1b", "are widely expressed. bmpr1b shows", "widely expressed. bmpr1b shows a", "expressed. bmpr1b shows a more", "bmpr1b shows a more restricted", "shows a more restricted expression", "a more restricted expression profile.", "more restricted expression profile. acvrl1", "restricted expression profile. acvrl1 is", "expression profile. acvrl1 is limited", "profile. acvrl1 is limited to", "acvrl1 is limited to endothelial", "is limited to endothelial cells", "limited to endothelial cells and", "to endothelial cells and a", "endothelial cells and a few", "cells and a few other", "and a few other cell", "a few other cell types.", "few other cell types. the", "other cell types. the binding", "cell types. the binding specificities", "types. the binding specificities of", "the binding specificities of bmps", "binding specificities of bmps to", "specificities of bmps to type", "of bmps to type i", "bmps to type i receptors", "to type i receptors is", "type i receptors is affected", "i receptors is affected by", "receptors is affected by the", "is affected by the type", "affected by the type ii", "by the type ii receptors", "the type ii receptors that", "type ii receptors that are", "ii receptors that are present", "that are present yu", "are present yu et", "present yu et al.", "yu et al. 2005 .", "et al. 2005 . typically", "2005 . typically bmp2", ". typically bmp2 and", "typically bmp2 and bmp4", "bmp2 and bmp4 bind to", "and bmp4 bind to bmpr1a", "bmp4 bind to bmpr1a and", "bind to bmpr1a and bmpr1b", "bmpr1a and bmpr1b ten", "and bmpr1b ten dijke", "bmpr1b ten dijke et", "ten dijke et al. 1994", "dijke et al. 1994 .", "et al. 1994 . bmp6", "al. 1994 . bmp6 and", "1994 . bmp6 and bmp7", ". bmp6 and bmp7 bind", "bmp6 and bmp7 bind strongly", "and bmp7 bind strongly to", "bmp7 bind strongly to acvr1", "bind strongly to acvr1 and", "strongly to acvr1 and weakly", "to acvr1 and weakly to", "acvr1 and weakly to bmpr1b.", "and weakly to bmpr1b. growth/differentiation", "weakly to bmpr1b. growth/differentiation factor", "to bmpr1b. growth/differentiation factor 5", "growth/differentiation factor 5 bmp14", "5 bmp14 gdf5", "bmp14 gdf5 preferentially", "gdf5 preferentially binds to", "binds to bmpr1b but", "to bmpr1b but not", "bmpr1b but not to", "but not to other type", "not to other type i", "to other type i receptors", "type i receptors nishitoh", "i receptors nishitoh et", "receptors nishitoh et al.", "nishitoh et al. 1995 .", "et al. 1995 . bmp9", "al. 1995 . bmp9 and", "1995 . bmp9 and bmp10", ". bmp9 and bmp10 bind", "bmp9 and bmp10 bind to", "and bmp10 bind to acvrl1", "bmp10 bind to acvrl1 and", "bind to acvrl1 and acvrl", "acvrl1 and acvrl scharpfenecker", "and acvrl scharpfenecker et", "acvrl scharpfenecker et al.", "scharpfenecker et al. 2007 .", "et al. 2007 . bmp", "al. 2007 . bmp type", "2007 . bmp type i", ". bmp type i receptors", "bmp type i receptors are", "type i receptors are shared", "i receptors are shared by", "receptors are shared by other", "are shared by other members", "shared by other members of", "by other members of the", "other members of the tgfb", "members of the tgfb family.", "of the tgfb family. three", "the tgfb family. three receptors", "family. three receptors bone", "three receptors bone morphogenetic", "receptors bone morphogenetic protein", "morphogenetic protein receptor type 2", "receptor type 2 bmpr2", "bmpr2 activin receptor", "receptor type 2a acvr2a", "2a acvr2a and", "acvr2a and activin receptor", "and activin receptor type 2b", "receptor type 2b acvr2b", "2b acvr2b are", "acvr2b are the type", "are the type ii receptors", "the type ii receptors for", "type ii receptors for mammalian", "ii receptors for mammalian bmps.", "receptors for mammalian bmps. they", "for mammalian bmps. they are", "mammalian bmps. they are widely", "bmps. they are widely expressed", "they are widely expressed in", "are widely expressed in various", "widely expressed in various tissues.", "expressed in various tissues. bmpr2", "in various tissues. bmpr2 is", "various tissues. bmpr2 is specific", "tissues. bmpr2 is specific for", "bmpr2 is specific for bmps", "specific for bmps whereas", "for bmps whereas acvr2a", "bmps whereas acvr2a and", "whereas acvr2a and acvr2b are", "acvr2a and acvr2b are shared", "and acvr2b are shared with", "acvr2b are shared with activins", "are shared with activins and", "shared with activins and myostatin.", "with activins and myostatin. bmp", "activins and myostatin. bmp binding", "and myostatin. bmp binding and", "myostatin. bmp binding and signalling", "bmp binding and signalling can", "binding and signalling can be", "and signalling can be affected", "signalling can be affected by", "can be affected by coreceptors.", "be affected by coreceptors. glycosylphosphatidylinositol", "by coreceptors. glycosylphosphatidylinositol gpi", "glycosylphosphatidylinositol gpi anchored", "gpi anchored proteins of", "anchored proteins of the repulsive", "proteins of the repulsive guidance", "of the repulsive guidance molecule", "repulsive guidance molecule rgm", "molecule rgm family", "rgm family including", "rgma rgmb dragon", "rgmb dragon and", "hemojuvelin hfe2 rgmc", "hfe2 rgmc are", "rgmc are coreceptors for", "are coreceptors for bmp2 and", "coreceptors for bmp2 and bmp4", "bmp2 and bmp4 enhancing", "and bmp4 enhancing signaling", "enhancing signaling samad et", "signaling samad et al.", "et al. 2005 babitt", "al. 2005 babitt et", "2005 babitt et al.", "et al. 2005 2006", "al. 2005 2006 .", "2005 2006 . they", "2006 . they interact with", ". they interact with bmp", "they interact with bmp type", "interact with bmp type i", "with bmp type i and/or", "bmp type i and/or type", "type i and/or type ii", "i and/or type ii receptors", "and/or type ii receptors and", "type ii receptors and bind", "ii receptors and bind bmp2", "receptors and bind bmp2 and", "and bind bmp2 and bmp4", "bmp2 and bmp4 but", "and bmp4 but not", "bmp4 but not bmp7", "but not bmp7 or tgfb1.", "not bmp7 or tgfb1. bmp2/4", "bmp7 or tgfb1. bmp2/4 signalling", "or tgfb1. bmp2/4 signalling normally", "tgfb1. bmp2/4 signalling normally involves", "bmp2/4 signalling normally involves bmpr2", "normally involves bmpr2 not", "involves bmpr2 not acvr2a", "bmpr2 not acvr2a or", "not acvr2a or acvr2b. cells", "acvr2a or acvr2b. cells transfected", "or acvr2b. cells transfected with", "acvr2b. cells transfected with rgma", "cells transfected with rgma use", "transfected with rgma use both", "with rgma use both bmpr2", "rgma use both bmpr2 and", "use both bmpr2 and acvr2a", "both bmpr2 and acvr2a for", "bmpr2 and acvr2a for bmp", "and acvr2a for bmp 2/4", "acvr2a for bmp 2/4 signalling", "bmp 2/4 signalling suggesting", "2/4 signalling suggesting that", "signalling suggesting that rgma", "suggesting that rgma facilitates the", "that rgma facilitates the use", "rgma facilitates the use of", "facilitates the use of acvr2a", "the use of acvr2a by", "use of acvr2a by bmp2/4", "acvr2a by bmp2/4 xia", "by bmp2/4 xia et", "bmp2/4 xia et al.", "xia et al. 2007 .", "et al. 2007 . endoglin", "2007 . endoglin eng", "endoglin eng is", "eng is a transmembrane", "is a transmembrane protein expressed", "a transmembrane protein expressed in", "transmembrane protein expressed in proliferating", "protein expressed in proliferating endothelial", "expressed in proliferating endothelial cells.", "in proliferating endothelial cells. it", "proliferating endothelial cells. it binds", "endothelial cells. it binds various", "cells. it binds various ligands", "it binds various ligands including", "binds various ligands including tgfb1/3", "ligands including tgfb1/3 activin", "including tgfb1/3 activin a", "tgfb1/3 activin a and", "a and bmp2/7 barbara", "and bmp2/7 barbara et", "bmp2/7 barbara et al.", "barbara et al. 1999 .", "et al. 1999 . it", "al. 1999 . it inhibits", "1999 . it inhibits tgfb", ". it inhibits tgfb induced", "it inhibits tgfb induced responses", "inhibits tgfb induced responses and", "tgfb induced responses and enhances", "induced responses and enhances bmp7", "responses and enhances bmp7 induced", "and enhances bmp7 induced responses", "bmp7 induced responses scherner", "induced responses scherner et", "responses scherner et al.", "scherner et al. 2007 .", "et al. 2007 . mutations", "al. 2007 . mutations in", "2007 . mutations in eng", ". mutations in eng result", "mutations in eng result in", "in eng result in hereditary", "eng result in hereditary haemorrhagic", "result in hereditary haemorrhagic telangiectasia", "hereditary haemorrhagic telangiectasia hht1", "hht1 also known", "also known as oslerweberrendu disease", "as oslerweberrendu disease while", "oslerweberrendu disease while mutations", "disease while mutations in", "while mutations in acvrl1 lead", "mutations in acvrl1 lead to", "in acvrl1 lead to hht2", "lead to hht2 suggesting", "to hht2 suggesting that", "hht2 suggesting that they", "suggesting that they act in", "that they act in a", "they act in a common", "act in a common signalling", "in a common signalling pathway", "common signalling pathway mcallister", "signalling pathway mcallister et", "pathway mcallister et al.", "et al. 1994 johnson", "al. 1994 johnson et", "1994 johnson et al.", "johnson et al. 1996 .", "et al. 1996 . bmp2", "al. 1996 . bmp2 is", "1996 . bmp2 is a", ". bmp2 is a dimeric", "bmp2 is a dimeric protein", "a dimeric protein having", "dimeric protein having two", "protein having two receptor", "having two receptor binding motifs.", "two receptor binding motifs. one", "receptor binding motifs. one is", "binding motifs. one is a", "motifs. one is a high", "one is a high affinity", "is a high affinity binding", "a high affinity binding site", "high affinity binding site for", "affinity binding site for bmpr1a", "site for bmpr1a the", "for bmpr1a the other", "bmpr1a the other is", "the other is a low", "other is a low affinity", "is a low affinity binding", "a low affinity binding site", "low affinity binding site for", "affinity binding site for bmpr2", "site for bmpr2 kirsch", "for bmpr2 kirsch et", "bmpr2 kirsch et al.", "kirsch et al. 2000 .", "et al. 2000 . in", "al. 2000 . in the", "2000 . in the absence", ". in the absence of", "in the absence of ligand", "the absence of ligand stimulation", "of ligand stimulation small", "ligand stimulation small fractions", "stimulation small fractions of", "small fractions of type ii", "fractions of type ii and", "of type ii and type", "ii and type i receptors", "and type i receptors are", "type i receptors are present", "i receptors are present as", "receptors are present as preexisting", "are present as preexisting homodimers", "present as preexisting homodimers and", "as preexisting homodimers and heterodimers", "preexisting homodimers and heterodimers on", "homodimers and heterodimers on the", "and heterodimers on the cell", "heterodimers on the cell surface.", "on the cell surface. ligand", "the cell surface. ligand binding", "cell surface. ligand binding increases", "surface. ligand binding increases oligomerization.", "ligand binding increases oligomerization. the", "binding increases oligomerization. the intracellular", "increases oligomerization. the intracellular domains", "oligomerization. the intracellular domains of", "the intracellular domains of type", "intracellular domains of type i", "domains of type i receptors", "of type i receptors have", "type i receptors have a", "i receptors have a characteristic", "receptors have a characteristic gs", "have a characteristic gs domain", "characteristic gs domain glycine", "gs domain glycine and", "domain glycine and serine", "glycine and serine rich domain", "serine rich domain located", "rich domain located n", "domain located n terminal", "located n terminal to the", "n terminal to the serine", "terminal to the serine threonine", "to the serine threonine kinase", "the serine threonine kinase domains.", "serine threonine kinase domains. type", "threonine kinase domains. type ii", "kinase domains. type ii receptor", "domains. type ii receptor kinases", "type ii receptor kinases are", "ii receptor kinases are constitutively", "receptor kinases are constitutively active", "kinases are constitutively active in", "are constitutively active in the", "constitutively active in the absence", "active in the absence of", "in the absence of ligand.", "the absence of ligand. upon", "absence of ligand. upon ligand", "of ligand. upon ligand binding", "upon ligand binding the", "ligand binding the type", "binding the type ii", "type ii receptor kinase phosphorylates", "ii receptor kinase phosphorylates the", "receptor kinase phosphorylates the gs", "kinase phosphorylates the gs domain", "phosphorylates the gs domain of", "the gs domain of the", "gs domain of the type", "domain of the type i", "of the type i receptor", "type i receptor a", "i receptor a critical", "receptor a critical event", "a critical event in signal", "critical event in signal transduction", "event in signal transduction by", "in signal transduction by the", "signal transduction by the serine/threonine", "transduction by the serine/threonine kinase", "by the serine/threonine kinase receptors", "serine/threonine kinase receptors miyazono", "kinase receptors miyazono et", "receptors miyazono et al.", "et al. 2010 . activation", "al. 2010 . activation of", "2010 . activation of the", ". activation of the tgfbr1", "activation of the tgfbr1 receptor", "of the tgfbr1 receptor has", "the tgfbr1 receptor has been", "tgfbr1 receptor has been studied", "receptor has been studied in", "has been studied in detail.", "been studied in detail. the", "studied in detail. the inactive", "in detail. the inactive conformation", "detail. the inactive conformation is", "the inactive conformation is maintained", "inactive conformation is maintained by", "conformation is maintained by interaction", "is maintained by interaction between", "maintained by interaction between the", "by interaction between the gs", "interaction between the gs domain", "the gs domain the", "gs domain the n", "domain the n terminal", "the n terminal lobe and", "n terminal lobe and the", "terminal lobe and the activation", "lobe and the activation loop", "and the activation loop of", "the activation loop of the", "activation loop of the kinase", "of the kinase huse", "the kinase huse et", "kinase huse et al.", "huse et al. 1999 .", "et al. 1999 . when", "al. 1999 . when the", "1999 . when the gs", ". when the gs domain", "when the gs domain is", "the gs domain is phosphorylated", "gs domain is phosphorylated by", "domain is phosphorylated by the", "is phosphorylated by the type", "phosphorylated by the type ii", "by the type ii receptor", "ii receptor kinase the", "receptor kinase the tgfbr1", "kinase the tgfbr1 kinase", "the tgfbr1 kinase is converted", "tgfbr1 kinase is converted to", "kinase is converted to an", "is converted to an active", "converted to an active conformation.", "to an active conformation. mutations", "an active conformation. mutations of", "active conformation. mutations of thr", "conformation. mutations of thr 204", "mutations of thr 204 in", "of thr 204 in tgfbr1", "thr 204 in tgfbr1 and", "204 in tgfbr1 and the", "in tgfbr1 and the corresponding", "tgfbr1 and the corresponding gln", "and the corresponding gln in", "the corresponding gln in bmp", "corresponding gln in bmp type", "gln in bmp type i", "in bmp type i receptors", "bmp type i receptors lead", "type i receptors lead to", "i receptors lead to their", "receptors lead to their constitutive", "lead to their constitutive activation.", "to their constitutive activation. the", "their constitutive activation. the l45", "constitutive activation. the l45 loop", "the l45 loop in", "l45 loop in the", "loop in the kinase", "in the kinase domain of", "kinase domain of type", "domain of type i", "type i receptors specifically", "i receptors specifically interacts", "receptors specifically interacts with", "specifically interacts with receptor regulated", "interacts with receptor regulated smads", "receptor regulated smads r", "regulated smads r smads", "smads r smads .", "r smads . neurotrophic tyrosine", "smads . neurotrophic tyrosine kinase", ". neurotrophic tyrosine kinase receptor", "neurotrophic tyrosine kinase receptor type", "tyrosine kinase receptor type 3", "receptor type 3 nt", "type 3 nt 3", "3 nt 3 growth", "nt 3 growth factor receptor", "growth factor receptor trkc", "receptor trkc ntrk3", "trkc ntrk3 directly", "ntrk3 directly binds bmpr2", "directly binds bmpr2 interfereing", "binds bmpr2 interfereing with", "bmpr2 interfereing with its", "interfereing with its interaction with", "with its interaction with bmpr1a", "interaction with bmpr1a which", "with bmpr1a which inhibits", "bmpr1a which inhibits downstream", "inhibits downstream signalling jin", "downstream signalling jin et", "signalling jin et al.", "jin et al. 2007 .", "et al. 2007 . tyrosine", "al. 2007 . tyrosine protein", "2007 . tyrosine protein kinase", ". tyrosine protein kinase transmembrane", "tyrosine protein kinase transmembrane receptor", "protein kinase transmembrane receptor ror2", "kinase transmembrane receptor ror2 and", "transmembrane receptor ror2 and bmpr1b", "receptor ror2 and bmpr1b form", "ror2 and bmpr1b form a", "and bmpr1b form a heteromeric", "bmpr1b form a heteromeric complex", "form a heteromeric complex in", "a heteromeric complex in a", "heteromeric complex in a ligand", "complex in a ligand independent", "in a ligand independent fashion", "a ligand independent fashion that", "ligand independent fashion that modulatesgdf5", "independent fashion that modulatesgdf5 bmpr1b", "fashion that modulatesgdf5 bmpr1b signalling", "that modulatesgdf5 bmpr1b signalling by", "modulatesgdf5 bmpr1b signalling by inhibition", "bmpr1b signalling by inhibition of", "signalling by inhibition of smad1/5", "by inhibition of smad1/5 signalling", "of smad1/5 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unknown.", "them are largely unknown. smad4", "are largely unknown. smad4 is", "largely unknown. smad4 is the", "unknown. smad4 is the only", "smad4 is the only co", "is the only co smad", "the only co smad in", "only co smad in mammals", "smad in mammals shared", "in mammals shared by", "mammals shared by both", "shared by both bmp and", "by both bmp and tgfb/activin", "both bmp and tgfb/activin signalling", "bmp and tgfb/activin signalling pathways.", "and tgfb/activin signalling pathways. smad6", "tgfb/activin signalling pathways. smad6 and", "signalling pathways. smad6 and smad7", "pathways. smad6 and smad7 are", "smad6 and smad7 are i", "and smad7 are i smads." ] }, { "record_id": "GLY_000594_1_179", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "201681", "r hsa", "hsa 201681", "r hsa 201681" ] }, { "record_id": "GLY_000594_1_179", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tcf 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.", "dvl interacts", "interacts with", "with phosphatidylinositol", "phosphatidylinositol 4", "4 kinase", "kinase type", "type ii", "and phophatidylinositol", "phophatidylinositol 4", "4 phosphate", "phosphate 5", "5 kinase", "type i", "to promote", "promote formation", "formation of", "of phosphatidylinositol", "4 5", "5 bisphosphate", "pi 4", "5 p2", "the membrane", "which is", "is required", "required for", "for the", "the clustering", "clustering and", "and phosphorylation", "phosphorylation of", "of lrp6", "lrp6 and", "the recruitment", "pan et", "qin et", "2009 .", "the three human", "three human dishevelled", "dishevelled dvl", "dvl proteins", "proteins play a", "play a central", "a central and", "central and overlapping", "and overlapping role", "overlapping role in", "role in the", "in the transduction", "the transduction of", "transduction of the", "of the wnt", "the wnt signaling", "wnt signaling cascade", "cascade lee", "lee et al", "al 2008", "2008 reviewed", "reviewed in 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"2001 cong et", "et al 2004", "2004 ossipova et", "et al 2005", "al 2005 .", "2005 . upon", ". upon pathway", "pathway activation phosphorylated", "activation phosphorylated dvl", "phosphorylated dvl translocates to", "dvl translocates to the", "translocates to the plasma", "to the plasma membrane", "the plasma membrane through", "plasma membrane through an", "membrane through an interaction", "through an interaction between", "an interaction between the", "interaction between the dvl", "between the dvl pdz", "the dvl pdz domain", "dvl pdz domain and", "pdz domain and the", "domain and the fzd", "and the fzd ktxxxw", "the fzd ktxxxw motif", "ktxxxw motif wong", "motif wong et", "et al 2003", "2003 umbhauer et", "et al 2000", "2000 kikuchi et", "et al 2011", "al 2011 .", "2011 . at", ". at the", "at the plasma membrane", "plasma membrane dvl", "membrane dvl is", "dvl is believed to", "is believed to oligomerize", "believed to oligomerize through", "to oligomerize through its", "oligomerize through its dix", "through its dix domain", "dix domain providing", "domain providing a", "providing a platform for", "a platform for axin", "platform for axin recruitment", "axin recruitment recruitment", "recruitment recruitment of", "recruitment of axin is", "of axin is also", "axin is also facilitated", "is also facilitated by", "also facilitated by interaction", "facilitated by interaction with", "by interaction with lrp", "with lrp schwarz", "lrp schwarz romond", "schwarz romond et al", "et al 2007", "2007 mao et", "al 2001 .", "2001 . dvl", ". dvl interacts", "dvl interacts with phosphatidylinositol", "interacts with phosphatidylinositol 4", "with phosphatidylinositol 4 kinase", "phosphatidylinositol 4 kinase type", "4 kinase type ii", "type ii pi4kii", "pi4kii and phophatidylinositol", "and phophatidylinositol 4 phosphate", "phophatidylinositol 4 phosphate 5", "4 phosphate 5 kinase", "phosphate 5 kinase type", "5 kinase type i", "type i pip5ki", "pip5ki to promote", "to promote formation of", "promote formation of phosphatidylinositol", "formation of phosphatidylinositol 4", "of phosphatidylinositol 4 5", "phosphatidylinositol 4 5 bisphosphate", "5 bisphosphate pi", "bisphosphate pi 4", "pi 4 5 p2", "5 p2 in", "p2 in the", "the membrane which", "membrane which is", "which is required for", "is required for the", "required for the clustering", "for the clustering and", "the clustering and phosphorylation", "clustering and phosphorylation of", "and phosphorylation of lrp6", "phosphorylation of lrp6 and", "of lrp6 and the", "lrp6 and the recruitment", "and the recruitment of", "the recruitment of axin", "of axin pan", "axin pan et", "2008 qin et", "et al 2009", "al 2009 .", "three human dishevelled dvl", "dishevelled dvl proteins", "dvl proteins play a", "proteins play a central and", "play a central and overlapping", "a central and overlapping role", "central and overlapping role in", "and overlapping role in the", "overlapping role in the transduction", "role in the transduction of", "in the transduction of the", "the transduction of the wnt", "transduction of the wnt signaling", "of the wnt signaling cascade", "wnt signaling cascade lee", "signaling cascade lee et", "cascade lee et al", "lee et al 2008", "al 2008 reviewed", "2008 reviewed in gao", "reviewed in gao and chen", "in gao and chen 2010", "gao and chen 2010 .", "chen 2010 . dvl", "2010 . dvl activity", ". dvl activity is", "dvl activity is regulated by", "activity is regulated by phosphorylation", "regulated by phosphorylation although", "by phosphorylation although the", "phosphorylation although the details", "although the details are not", "the details are not completely", "details are not completely worked", "are not completely worked out.", "completely worked out. dvl", "worked out. dvl likely", "out. dvl likely exists", "dvl likely exists as a", "likely exists as a phosphoprotein", "exists as a phosphoprotein even", "as a phosphoprotein even in", "a phosphoprotein even in the", "phosphoprotein even in the absence", "even in the absence of", "in the absence of wnt", "the absence of wnt stimulation", "of wnt stimulation and", "wnt stimulation and is", "stimulation and is further", "and is further phosphorylated upon", "is further phosphorylated upon ligand", "further phosphorylated upon ligand binding.", "upon ligand binding. casein", "ligand binding. casein kinase", "binding. casein kinase 1epsilon", "casein kinase 1epsilon csnk1e", "csnk1e casein kinase", "casein kinase 2 csnk2", "2 csnk2 and", "csnk2 and par1 have", "and par1 have all been", "par1 have all been reported", "have all been reported to", "all been reported to phosphorylate", "been reported to phosphorylate dvl", "to phosphorylate dvl willert", "phosphorylate dvl willert et", "dvl willert et al", "willert et al 1997", "al 1997 sun", "1997 sun et al", "sun et al 2001", "al 2001 cong", "2001 cong et al", "cong et al 2004", "al 2004 ossipova", "2004 ossipova et al", "ossipova et al 2005", "et al 2005 .", "2005 . upon pathway", ". upon pathway activation", "upon pathway activation phosphorylated", "pathway activation phosphorylated dvl", "activation phosphorylated dvl translocates", "phosphorylated dvl translocates to the", "dvl translocates to the plasma", "translocates to the plasma membrane", "to the plasma membrane through", "the plasma membrane through an", "plasma membrane through an interaction", "membrane through an interaction between", "through an interaction between the", "an interaction between the dvl", "interaction between the dvl pdz", "between the dvl pdz domain", "the dvl pdz domain and", "dvl pdz domain and the", "pdz domain and the fzd", "domain and the fzd ktxxxw", "and the fzd ktxxxw motif", "fzd ktxxxw motif wong", "ktxxxw motif wong et", "motif wong et al", "wong et al 2003", "al 2003 umbhauer", "2003 umbhauer et al", "umbhauer et al 2000", "al 2000 kikuchi", "2000 kikuchi et al", "kikuchi et al 2011", "et al 2011 .", "2011 . at the", ". at the plasma", "the plasma membrane dvl", "plasma membrane dvl is", "membrane dvl is believed", "dvl is believed to oligomerize", "is believed to oligomerize through", "believed to oligomerize through its", "to oligomerize through its dix", "oligomerize through its dix domain", "its dix domain providing", "dix domain providing a", "domain providing a platform", "providing a platform for axin", "a platform for axin recruitment", "for axin recruitment recruitment", "axin recruitment recruitment of", "recruitment recruitment of axin", "recruitment of axin is also", "of axin is also facilitated", "axin is also facilitated by", "is also facilitated by interaction", "also facilitated by interaction with", "facilitated by interaction with lrp", "interaction with lrp schwarz", "with lrp schwarz romond", "lrp schwarz romond et", "romond et al 2007", "al 2007 mao", "2007 mao et al", "mao et al 2001", "et al 2001 .", "2001 . dvl interacts", ". dvl interacts with", "dvl interacts with phosphatidylinositol 4", "interacts with phosphatidylinositol 4 kinase", "with phosphatidylinositol 4 kinase type", "phosphatidylinositol 4 kinase type ii", "kinase type ii pi4kii", "ii pi4kii and", "pi4kii and phophatidylinositol 4", "and phophatidylinositol 4 phosphate 5", "phophatidylinositol 4 phosphate 5 kinase", "4 phosphate 5 kinase type", "phosphate 5 kinase type i", "kinase type i pip5ki", "i pip5ki to", "pip5ki to promote formation", "to promote formation of phosphatidylinositol", "promote formation of phosphatidylinositol 4", "formation of phosphatidylinositol 4 5", "of phosphatidylinositol 4 5 bisphosphate", "4 5 bisphosphate pi", "5 bisphosphate pi 4", "bisphosphate pi 4 5", "4 5 p2 in", "5 p2 in the", "p2 in the membrane", "in the membrane which", "the membrane which is", "membrane which is required", "which is required for the", "is required for the clustering", "required for the clustering and", "for the clustering and phosphorylation", "the clustering and phosphorylation of", "clustering and phosphorylation of lrp6", "and phosphorylation of lrp6 and", "phosphorylation of lrp6 and the", "of lrp6 and the recruitment", "lrp6 and the recruitment of", "and the recruitment of axin", "recruitment of axin pan", "of axin pan et", "axin pan et al", "pan et al 2008", "al 2008 qin", "2008 qin et al", "qin et al 2009", "et al 2009 ." ] }, { "record_id": "GLY_000594_1_181", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "201722", "r hsa", "hsa 201722", "r hsa 201722" ] }, { "record_id": "GLY_000594_1_181", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of the", "the beta", "beta catenin:tcf", "catenin:tcf transactivating", "transactivating complex", "formation of the", "of the beta", "the beta catenin:tcf", "beta catenin:tcf transactivating", "catenin:tcf transactivating complex", "formation of the beta", "of the beta catenin:tcf", "the beta 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proteins", "proteins recruit", "recruit groucho/tle", "groucho/tle repressors", "repressors to", "to inhibit", "inhibit transcription", "upon wnt", "wnt stimulation", "catenin can", "can displace", "displace groucho/tle", "groucho/tle from", "from tcf/lef", "proteins to", "to initiate", "initiate transcriptional", "transcriptional activation", "in chen", "chen and", "and courey", "2000 .", "although this", "this model", "model for", "for wnt", "wnt dependent", "dependent activation", "activation of", "of target", "genes is", "is widely", "widely accepted", "it is", "is important", "important to", "to note", "note that", "that tcf/lef", "proteins are", "are not", "not redundant", "redundant and", "and can", "can contribute", "contribute to", "gene expression", "expression in", "in a", "a number", "number of", "of different", "different ways", "macdonald et", "2009 .", "in particular", "is thought", "thought to", "to have", "have a", "a more", "more pronounced", "pronounced repressor", "repressor function", "function than", "than other", "other tcf/lef", "tcf/lef family", "family members.", "a couple", "couple of", "of recent", "recent studies", "studies in", "in xenopus", "xenopus and", "and mammalian", "mammalian cells", "cells show", "show that", "that wnt", "and beta", "catenin dependent", "dependent phosphorylation", "phosphorylation of", "of tcf7l1", "tcf7l1 tcf3", "promotes its", "its dissociation", "dissociation from", "from the", "the promoter", "promoter of", "genes and", "and allows", "allows gene", "expression through", "through relief", "relief of", "of this", "this repression", "repression activity", "hikasa et", "2011 .


the", ".


the role", "role of", "of beta", "catenin at", "at wnt", "wnt promoters", "promoters hinges", "hinges upon", "upon its", "its ability", "ability to", "to act", "act as", "as a", "a scaffold", "scaffold for", "for the", "the recruitment", "recruitment of", "of other", "other proteins.", "proteins. the", "the structure", "structure of", "catenin consists", "of 12", "12 imperfect", "imperfect arm", "arm repeats", "r1 12", "flanked by", "by an", "an n", "n terminal", "terminal and", "and c", "c terminal", "terminal extension", "ntd and", "and ctd", "ctd respectively", "with a", "a conserved", "conserved helix", "helix c", "c located", "located between", "between r12", "r12 and", "and the", "the ctd.", "nuclear beta", "catenin interacts", "interacts with", "tcf/lef at", "through arm", "arm domains", "domains 3", "3 9", "graham et", "poy et", "xing et", "2008 .", "the n", "n and", "the c", "terminal regions", "regions are", "are important", "important for", "of transcriptional", "transcriptional activator", "activator and", "and repressors", "repressors that", "that contribute", "in mosimann", "mosimann et", "valenta et", "2012 .", "terminal arm", "domains 1", "1 4", "4 recruit", "recruit the", "wnt pathway", "pathway specific", "specific activators", "activators bcl9:pygo", "bcl9:pygo while", "while the", "terminal region", "r11 ctd", "a wide", "wide range", "range of", "of general", "general transcriptional", "transcriptional activators", "activators that", "that are", "are involved", "involved in", "in chromatin", "chromatin remodelling", "remodelling and", "and transcription", "transcription initiation.", "initiation. these", "these include", "include hats", "hats such", "such as", "as p300", "cbp and", "and tip60", "histone methyltransferases", "methyltransferases such", "as mll1", "mll1 and", "and 2", "swi/snf factors", "factors brg1", "brg1 and", "and iswi", "iswi and", "and components", "components of", "the paf", "paf complex", "although many", "many binding", "binding partners", "partners have", "have been", "been identified", "identified for", "region of", "in many", "many cases", "cases the", "the timing", "timing and", "and relationship", "relationship of", "of these", "these interactions", "interactions and", "and indeed", "the exact", "exact complex", "complex composition", "composition remains", "remains to", "to be", "be elucidated.", "because many", "many of", "the interacting", "interacting partners", "partners appear", "appear to", "to bind", "to overlapping", "overlapping regions", "regions of", "is unlikely", "unlikely that", "that they", "they all", "all bind", "bind simultaneously.", "for simplicity", "the interactions", "interactions have", "been depicted", "depicted as", "as though", "though they", "they occur", "occur independently", "independently of", "of one", "one another", "more accurately", "accurately they", "they are", "are likely", "likely to", "to cycle", "cycle successively", "successively on", "on and", "and off", "off beta", "catenin to", "to promote", "promote an", "an active", "active chromatin", "chromatin structure", "in willert", "willert and", "and jones", "once in the", "in the nucleus", "nucleus beta", "beta catenin is", "catenin is recruited", "is recruited to", "recruited to wnt", "to wnt target", "wnt target genes", "target genes through", "genes through interaction", "through interaction with", "interaction with tcf/lef", "with tcf/lef transcription", "tcf/lef transcription factors.", "transcription factors. this", "factors. this family", "family which", "which consists of", "consists of tcf7", "tcf7 also", "also known as", "known as tcf1", "tcf7l1 also", "known as tcf3", "tcf7l2 also", "known as tcf4", "tcf4 and", "tcf7l3 also", "known as lef1", "are hmg containing", "hmg containing transcription", "containing transcription factors", "transcription factors that", "factors that bind", "that bind to", "bind to the", "to the wnt", "the wnt responsive", "wnt responsive elements", "responsive elements in", "elements in target", "in target gene", "target gene promoters", "promoters reviewed", "reviewed in brantjes", "in brantjes et", "brantjes et al", "al 2002", ". in", "in the absence", "the absence of", "absence of wnt", "of wnt signal", "signal tcf/lef", "tcf/lef proteins recruit", "proteins recruit groucho/tle", "recruit groucho/tle repressors", "groucho/tle repressors to", "repressors to inhibit", "to inhibit transcription", "transcription upon", "upon wnt stimulation", "stimulation beta", "beta catenin can", "catenin can displace", "can displace groucho/tle", "displace groucho/tle from", "groucho/tle from tcf/lef", "from tcf/lef proteins", "tcf/lef proteins to", "proteins to initiate", "to initiate transcriptional", "initiate transcriptional activation", "activation reviewed", "reviewed in chen", "in chen and", "chen and courey", "courey 2000", ". although", "although this model", "this model for", "model for wnt", "for wnt dependent", "wnt dependent activation", "dependent activation of", "activation of target", "of target genes", "target genes is", "genes is widely", "is widely accepted", "accepted it", "it is important", "is important to", "important to note", "to note that", "note that tcf/lef", "that tcf/lef proteins", "tcf/lef proteins are", "proteins are not", "are not redundant", "not redundant and", "redundant and can", "and can contribute", "can contribute to", "contribute to wnt", "wnt target gene", "target gene expression", "gene expression in", "expression in a", "in a number", "a number of", "number of different", "of different ways", "ways reviewed", "2002 macdonald", "macdonald et al", "al 2009", "particular tcf7l1", "tcf3 is", "is thought to", "thought to have", "to have a", "have a more", "a more pronounced", "more pronounced repressor", "pronounced repressor function", "repressor function than", "function than other", "than other tcf/lef", "other tcf/lef family", "tcf/lef family members.", "members. a", "a couple of", "couple of recent", "of recent studies", "recent studies in", "studies in xenopus", "in xenopus and", "xenopus and mammalian", "and mammalian cells", "mammalian cells show", "cells show that", "show that wnt", "wnt and", "and beta catenin", "beta catenin dependent", "catenin dependent phosphorylation", "dependent phosphorylation of", "phosphorylation of tcf7l1", "of tcf7l1 tcf3", "tcf3 promotes", "promotes its dissociation", "its dissociation from", "dissociation from the", "from the promoter", "the promoter of", "promoter of target", "target genes and", "genes and allows", "and allows gene", "allows gene expression", "gene expression through", "expression through relief", "through relief of", "relief of this", "of this repression", "this repression activity", "activity hikasa", "hikasa et al", "al 2010", "2010 hikasa", "al 2011", "2011 .


the role", ".


the role of", "role of beta", "of beta catenin", "beta catenin at", "catenin at wnt", "at wnt promoters", "wnt promoters hinges", "promoters hinges upon", "hinges upon its", "upon its ability", "its ability to", "ability to act", "to act as", "act as a", "as a scaffold", "a scaffold for", "scaffold for the", "for the recruitment", "the recruitment of", "recruitment of other", "of other proteins.", "other proteins. the", "proteins. the structure", "the structure of", "structure of beta", "beta catenin consists", "catenin consists of", "consists of 12", "of 12 imperfect", "12 imperfect arm", "imperfect arm repeats", "repeats r1", "12 flanked", "flanked by an", "by an n", "an n terminal", "n terminal and", "terminal and c", "and c terminal", "c terminal extension", "extension ntd", "ntd and ctd", "and ctd respectively", "with a conserved", "a conserved helix", "conserved helix c", "helix c located", "c located between", "located between r12", "between r12 and", "r12 and the", "and the ctd.", "ctd. nuclear", "nuclear beta catenin", "beta catenin interacts", "catenin interacts with", "interacts with tcf/lef", "with tcf/lef at", "tcf/lef at wnt", "at wnt target", "genes through arm", "through arm domains", "arm domains 3", "domains 3 9", "9 graham", "graham et al", "al 2000", "2000 poy", "poy et al", "al 2001", "2001 xing", "xing et al", "al 2008", ". the", "the n and", "n and the", "and the c", "the c terminal", "c terminal regions", "terminal regions are", "regions are important", "are important for", "important for the", "recruitment of transcriptional", "of transcriptional activator", "transcriptional activator and", "activator and repressors", "and repressors that", "repressors that contribute", "that contribute to", "expression reviewed", "reviewed in mosimann", "in mosimann et", "mosimann et al", "2009 valenta", "valenta et al", "al 2012", "the n terminal", "n terminal arm", "terminal arm domains", "arm domains 1", "domains 1 4", "1 4 recruit", "4 recruit the", "recruit the wnt", "the wnt pathway", "wnt pathway specific", "pathway specific activators", "specific activators bcl9:pygo", "activators bcl9:pygo while", "bcl9:pygo while the", "while the c", "c terminal region", "region r11", "ctd interacts", "interacts with a", "with a wide", "a wide range", "wide range of", "range of general", "of general transcriptional", "general transcriptional activators", "transcriptional activators that", "activators that are", "that are involved", "are involved in", "involved in chromatin", "in chromatin remodelling", "chromatin remodelling and", "remodelling and transcription", "and transcription initiation.", "transcription initiation. these", "initiation. these include", "these include hats", "include hats such", "hats such as", "such as p300", "p300 cbp", "cbp and tip60", "tip60 histone", "histone methyltransferases such", "methyltransferases such as", "such as mll1", "as mll1 and", "mll1 and 2", "2 swi/snf", "swi/snf factors brg1", "factors brg1 and", "brg1 and iswi", "and iswi and", "iswi and components", "and components of", "components of the", "of the paf", "the paf complex", "complex reviewed", "although many binding", "many binding partners", "binding partners have", "partners have been", "have been identified", "been identified for", "identified for the", "for the c", "terminal region of", "region of beta", "catenin in", "in many cases", "many cases the", "cases the timing", "the timing and", "timing and relationship", "and relationship of", "relationship of these", "of these interactions", "these interactions and", "interactions and indeed", "indeed the", "the exact complex", "exact complex composition", "complex composition remains", "composition remains to", "remains to be", "to be elucidated.", "elucidated. moreover", "moreover because", "because many of", "many of the", "of the interacting", "the interacting partners", "interacting partners appear", "partners appear to", "appear to bind", "to bind to", "bind to overlapping", "to overlapping regions", "overlapping regions of", "regions of beta", "catenin it", "it is unlikely", "is unlikely that", "unlikely that they", "that they all", "they all bind", "all bind simultaneously.", "simultaneously. for", "simplicity the", "the interactions have", "interactions have been", "have been depicted", "been depicted as", "depicted as though", "as though they", "though they occur", "they occur independently", "occur independently of", "independently of one", "of one another", "another more", "more accurately they", "accurately they are", "they are likely", "are likely to", "likely to cycle", "to cycle successively", "cycle successively on", "successively on and", "on and off", "and off beta", "off beta catenin", "beta catenin to", "catenin to promote", "to promote an", "promote an active", "an active chromatin", "active chromatin structure", "structure reviewed", "reviewed in willert", "in willert and", "willert and jones", "jones 2006", "2006 valenta", "once in the nucleus", "the nucleus beta", "nucleus beta catenin", "beta catenin is recruited", "catenin is recruited to", "is recruited to wnt", "recruited to wnt target", "to wnt target genes", "wnt target genes through", "target genes through interaction", "genes through interaction with", "through interaction with tcf/lef", "interaction with tcf/lef transcription", "with tcf/lef transcription factors.", "tcf/lef transcription factors. this", "transcription factors. this family", "this family which", "family which consists", "which consists of tcf7", "of tcf7 also", "tcf7 also known", "also known as tcf1", "tcf1 tcf7l1", "tcf7l1 also known", "also known as tcf3", "tcf3 tcf7l2", "tcf7l2 also known", "also known as tcf4", "as tcf4 and", "tcf4 and tcf7l3", "and tcf7l3 also", "tcf7l3 also known", "also known as lef1", "lef1 are", "are hmg containing transcription", "hmg containing transcription factors", "containing transcription factors that", "transcription factors that bind", "factors that bind to", "that bind to the", "bind to the wnt", "to the wnt responsive", "the wnt responsive elements", "wnt responsive elements in", "responsive elements in target", "elements in target gene", "in target gene promoters", "gene promoters reviewed", "promoters reviewed in", "reviewed in brantjes et", "in brantjes et al", "et al 2002", "al 2002 .", "2002 . in", ". in the", "in the absence of", "the absence of wnt", "absence of wnt signal", "wnt signal tcf/lef", "signal tcf/lef proteins", "tcf/lef proteins recruit groucho/tle", "proteins recruit groucho/tle repressors", "recruit groucho/tle repressors to", "groucho/tle repressors to inhibit", "repressors to inhibit transcription", "inhibit transcription upon", "transcription upon wnt", "wnt stimulation beta", "stimulation beta catenin", "beta catenin can displace", "catenin can displace groucho/tle", "can displace groucho/tle from", "displace groucho/tle from tcf/lef", "groucho/tle from tcf/lef proteins", "from tcf/lef proteins to", "tcf/lef proteins to initiate", "proteins to initiate transcriptional", "to initiate transcriptional activation", "transcriptional activation reviewed", "activation reviewed in", "reviewed in chen and", "in chen and courey", "and courey 2000", "courey 2000 .", "2000 . although", ". although this", "although this model for", "this model for wnt", "model for wnt dependent", "for wnt dependent activation", "wnt dependent activation of", "dependent activation of target", "activation of target genes", "of target genes is", "target genes is widely", "genes is widely accepted", "widely accepted it", "accepted it is", "it is important to", "is important to note", "important to note that", "to note that tcf/lef", "note that tcf/lef proteins", "that tcf/lef proteins are", "tcf/lef proteins are not", "proteins are not redundant", "are not redundant and", "not redundant and can", "redundant and can contribute", "and can contribute to", "can contribute to wnt", "contribute to wnt target", "to wnt target gene", "wnt target gene expression", "target gene expression in", "gene expression in a", "expression in a number", "in a number of", "a number of different", "number of different ways", "different ways reviewed", "ways reviewed in", "2002 macdonald et", "et al 2009", "al 2009 .", "2009 . in", ". in particular", "in particular tcf7l1", "tcf3 is thought", "is thought to have", "thought to have a", "to have a more", "have a more pronounced", "a more pronounced repressor", "more pronounced repressor function", "pronounced repressor function than", "repressor function than other", "function than other tcf/lef", "than other tcf/lef family", "other tcf/lef family members.", "family members. a", "members. a couple", "a couple of recent", "couple of recent studies", "of recent studies in", "recent studies in xenopus", "studies in xenopus and", "in xenopus and mammalian", "xenopus and mammalian cells", "and mammalian cells show", "mammalian cells show that", "cells show that wnt", "that wnt and", "wnt and beta", "and beta catenin dependent", "beta catenin dependent phosphorylation", "catenin dependent phosphorylation of", "dependent phosphorylation of tcf7l1", "phosphorylation of tcf7l1 tcf3", "tcf7l1 tcf3 promotes", "tcf3 promotes its", "promotes its dissociation from", "its dissociation from the", "dissociation from the promoter", "from the promoter of", "the promoter of target", "promoter of target genes", "of target genes and", "target genes and allows", "genes and allows gene", "and allows gene expression", "allows gene expression through", "gene expression through relief", "expression through relief of", "through relief of this", "relief of this repression", "of this repression activity", "repression activity hikasa", "activity hikasa et", "et al 2010", "2010 hikasa et", "et al 2011", "al 2011 .


the", "2011 .


the role of", ".


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"terminal extension ntd", "extension ntd and", "ntd and ctd respectively", "respectively with", "with a conserved helix", "a conserved helix c", "conserved helix c located", "helix c located between", "c located between r12", "located between r12 and", "between r12 and the", "r12 and the ctd.", "the ctd. nuclear", "ctd. nuclear beta", "nuclear beta catenin interacts", "beta catenin interacts with", "catenin interacts with tcf/lef", "interacts with tcf/lef at", "with tcf/lef at wnt", "tcf/lef at wnt target", "at wnt target genes", "target genes through arm", "genes through arm domains", "through arm domains 3", "arm domains 3 9", "3 9 graham", "9 graham et", "et al 2000", "2000 poy et", "et al 2001", "2001 xing et", "et al 2008", "al 2008 .", "2008 . the", ". the n", "the n and the", "n and the c", "and the c terminal", "the c terminal regions", "c terminal regions are", "terminal regions are important", "regions are important for", "are important for the", "important for the recruitment", "the recruitment of transcriptional", "recruitment of transcriptional activator", "of transcriptional activator and", "transcriptional activator and repressors", "activator and repressors that", "and repressors that contribute", "repressors that contribute to", "that contribute to wnt", "gene expression reviewed", "expression reviewed in", "reviewed in mosimann et", "in mosimann et al", "2009 valenta et", "et al 2012", "al 2012 .", "2012 . the", "the n terminal arm", "n terminal arm domains", "terminal arm domains 1", "arm domains 1 4", "domains 1 4 recruit", "1 4 recruit the", "4 recruit the wnt", "recruit the wnt pathway", "the wnt pathway specific", "wnt pathway specific activators", "pathway specific activators bcl9:pygo", "specific activators bcl9:pygo while", "activators bcl9:pygo while the", "bcl9:pygo while the c", "while the c terminal", "the c terminal region", "terminal region r11", "region r11 ctd", "r11 ctd interacts", "ctd interacts with", "interacts with a wide", "with a wide range", "a wide range of", "wide range of general", "range of general transcriptional", "of general transcriptional activators", "general transcriptional activators that", "transcriptional activators that are", "activators that are involved", "that are involved in", "are involved in chromatin", "involved in chromatin remodelling", "in chromatin remodelling and", "chromatin remodelling and transcription", "remodelling and transcription initiation.", "and transcription initiation. these", "transcription initiation. these include", "initiation. these include hats", "these include hats such", "include hats such as", "hats such as p300", "as p300 cbp", "p300 cbp and", "and tip60 histone", "tip60 histone methyltransferases", "histone methyltransferases such as", "methyltransferases such as mll1", "such as mll1 and", "as mll1 and 2", "and 2 swi/snf", "2 swi/snf factors", "swi/snf factors brg1 and", "factors brg1 and iswi", "brg1 and iswi and", "and iswi and components", "iswi and components of", "and components of the", "components of the paf", "of the paf complex", "paf complex reviewed", "complex reviewed in", "2012 . although", ". although many", "although many binding partners", "many binding partners have", "binding partners have been", "partners have been identified", "have been identified for", "been identified for the", "identified for the c", "for the c terminal", "c terminal region of", "terminal region of beta", "region of beta catenin", "beta catenin in", "catenin in many", "in many cases the", "many cases the timing", "cases the timing and", "the timing and relationship", "timing and relationship of", "and relationship of these", "relationship of these interactions", "of these interactions and", "these interactions and indeed", "and indeed the", "indeed the exact", "the exact complex composition", "exact complex composition remains", "complex composition remains to", "composition remains to be", "remains to be elucidated.", "be elucidated. moreover", "moreover because many", "because many of the", "many of the interacting", "of the interacting partners", "the interacting partners appear", "interacting partners appear to", "partners appear to bind", "appear to bind to", "to bind to overlapping", "bind to overlapping regions", "to overlapping regions of", "overlapping regions of beta", "regions of beta catenin", "beta catenin it", "catenin it is", "it is unlikely that", "is unlikely that they", "unlikely that they all", "that they all bind", "they all bind simultaneously.", "bind simultaneously. for", "simultaneously. for simplicity", "for simplicity the", "simplicity the interactions", "the interactions have been", "interactions have been depicted", "have been depicted as", "been depicted as though", "depicted as though they", "as though they occur", "though they occur independently", "they occur independently of", "occur independently of one", "independently of one another", "one another more", "another more accurately", "more accurately they are", "accurately they are likely", "they are likely to", "are likely to cycle", "likely to cycle successively", "to cycle successively on", "cycle successively on and", "successively on and off", "on and off beta", "and off beta catenin", "off beta catenin to", "beta catenin to promote", "catenin to promote an", "to promote an active", "promote an active chromatin", "an active chromatin structure", "chromatin structure reviewed", "structure reviewed in", "reviewed in willert and", "in willert and jones", "and jones 2006", "2006 valenta et", "in the nucleus beta", "the nucleus beta catenin", "nucleus beta catenin is", "beta catenin is recruited to", "catenin is recruited to wnt", "is recruited to wnt target", "recruited to wnt target genes", "to wnt target genes through", "wnt target genes through interaction", "target genes through interaction with", "genes through interaction with tcf/lef", "through interaction with tcf/lef transcription", "interaction with tcf/lef transcription factors.", "with tcf/lef transcription factors. this", "tcf/lef transcription factors. this family", "factors. this family which", "this family which consists", "family which consists of", "consists of tcf7 also", "of tcf7 also known", "tcf7 also known as", "as tcf1 tcf7l1", "tcf7l1 also known as", "as tcf3 tcf7l2", "tcf7l2 also known as", "known as tcf4 and", "as tcf4 and tcf7l3", "and tcf7l3 also known", "tcf7l3 also known as", "as lef1 are", "lef1 are hmg", "are hmg containing transcription factors", "hmg containing transcription factors that", "containing transcription factors that bind", "transcription factors that bind to", "factors that bind to the", "that bind to the wnt", "bind to the wnt responsive", "to the wnt responsive elements", "the wnt responsive elements in", "wnt responsive elements in target", "responsive elements in target gene", "elements in target gene promoters", "target gene promoters reviewed", "gene promoters reviewed in", "promoters reviewed in brantjes", "reviewed in brantjes et al", "brantjes et al 2002", "et al 2002 .", "2002 . in the", ". in the absence", "in the absence of wnt", "the absence of wnt signal", "of wnt signal tcf/lef", "wnt signal tcf/lef proteins", "signal tcf/lef proteins recruit", "tcf/lef proteins recruit groucho/tle repressors", "proteins recruit groucho/tle repressors to", "recruit groucho/tle repressors to inhibit", "groucho/tle repressors to inhibit transcription", "to inhibit transcription upon", "inhibit transcription upon wnt", "transcription upon wnt stimulation", "upon wnt stimulation beta", "wnt stimulation beta catenin", "stimulation beta catenin can", "beta catenin can displace groucho/tle", "catenin can displace groucho/tle from", "can displace groucho/tle from tcf/lef", "displace groucho/tle from tcf/lef proteins", "groucho/tle from tcf/lef proteins to", "from tcf/lef proteins to initiate", "tcf/lef proteins to initiate transcriptional", "proteins to initiate transcriptional activation", "initiate transcriptional activation reviewed", "transcriptional activation reviewed in", "activation reviewed in chen", "reviewed in chen and courey", "chen and courey 2000", "and courey 2000 .", "2000 . although this", ". although this model", "although this model for wnt", "this model for wnt dependent", "model for wnt dependent activation", "for wnt dependent activation of", "wnt dependent activation of target", "dependent activation of target genes", "activation of target genes is", "of target genes is widely", "target genes is widely accepted", "is widely accepted it", "widely accepted it is", "accepted it is important", "it is important to note", "is important to note that", "important to note that tcf/lef", "to note that tcf/lef proteins", "note that tcf/lef proteins are", "that tcf/lef proteins are not", "tcf/lef proteins are not redundant", "proteins are not redundant and", "are not redundant and can", "not redundant and can contribute", "redundant and can contribute to", "and can contribute to wnt", "can contribute to wnt target", "contribute to wnt target gene", "to wnt target gene expression", "wnt target gene expression in", "target gene expression in a", "gene expression in a number", "expression in a number of", "in a number of different", "a number of different ways", "of different ways reviewed", "different ways reviewed in", "ways reviewed in brantjes", "al 2002 macdonald", "2002 macdonald et al", "macdonald et al 2009", "et al 2009 .", "2009 . in particular", "particular tcf7l1 tcf3", "tcf7l1 tcf3 is", "tcf3 is thought to", "is thought to have a", "thought to have a more", "to have a more pronounced", "have a more pronounced repressor", "a more pronounced repressor function", "more pronounced repressor function than", "pronounced repressor function than other", "repressor function than other tcf/lef", "function than other tcf/lef family", "than other tcf/lef family members.", "tcf/lef family members. a", "family members. a couple", "members. a couple of", "a couple of recent studies", "couple of recent studies in", "of recent studies in xenopus", "recent studies in xenopus and", "studies in xenopus and mammalian", "in xenopus and mammalian cells", "xenopus and mammalian cells show", "and mammalian cells show that", "mammalian cells show that wnt", "show that wnt and", "that wnt and beta", "wnt and beta catenin", "and beta catenin dependent phosphorylation", "beta catenin dependent phosphorylation of", "catenin dependent phosphorylation of tcf7l1", "dependent phosphorylation of tcf7l1 tcf3", "of tcf7l1 tcf3 promotes", "tcf7l1 tcf3 promotes its", "tcf3 promotes its dissociation", "promotes its dissociation from the", "its dissociation from the promoter", "dissociation from the promoter of", "from the promoter of target", "the promoter of target genes", "promoter of target genes and", "of target genes and allows", "target genes and allows gene", "genes and allows gene expression", "and allows gene expression through", "allows gene expression through relief", "gene expression through relief of", "expression through relief of this", "through relief of this repression", "relief of this repression activity", "this repression activity hikasa", "repression activity hikasa et", "activity hikasa et al", "hikasa et al 2010", "al 2010 hikasa", "2010 hikasa et al", "hikasa et al 2011", "et al 2011 .


the", "al 2011 .


the role", "2011 .


the role of beta", ".


the role of beta catenin", "role of beta catenin at", "of beta catenin at wnt", "beta catenin at wnt promoters", "catenin at wnt promoters hinges", "at wnt promoters hinges upon", "wnt promoters hinges upon its", "promoters hinges upon its ability", "hinges upon its ability to", "upon its ability to act", "its ability to act as", "ability to act as a", "to act as a scaffold", "act as a scaffold for", "as a scaffold for the", "a scaffold for the recruitment", "scaffold for the recruitment of", "for the recruitment of other", "the recruitment of other proteins.", "recruitment of other proteins. the", "of other proteins. the structure", "other proteins. the structure of", "proteins. the structure of beta", "the structure of beta catenin", "structure of beta catenin consists", "of beta catenin consists of", "beta catenin consists of 12", "catenin consists of 12 imperfect", "consists of 12 imperfect arm", "of 12 imperfect arm repeats", "imperfect arm repeats r1", "arm repeats r1 12", "r1 12 flanked by", "12 flanked by an", "flanked by an n terminal", "by an n terminal and", "an n terminal and c", "n terminal and c terminal", "terminal and c terminal extension", "c terminal extension ntd", "terminal extension ntd and", "extension ntd and ctd", "ctd respectively with", "respectively with a", "with a conserved helix c", "a conserved helix c located", "conserved helix c located between", "helix c located between r12", "c located between r12 and", "located between r12 and the", "between r12 and the ctd.", "and the ctd. nuclear", "the ctd. nuclear beta", "ctd. nuclear beta catenin", "nuclear beta catenin interacts with", "beta catenin interacts with tcf/lef", "catenin interacts with tcf/lef at", "interacts with tcf/lef at wnt", "with tcf/lef at wnt target", "tcf/lef at wnt target genes", "at wnt target genes through", "wnt target genes through arm", "target genes through arm domains", "genes through arm domains 3", "through arm domains 3 9", "domains 3 9 graham", "3 9 graham et", "9 graham et al", "graham et al 2000", "al 2000 poy", "2000 poy et al", "poy et al 2001", "al 2001 xing", "2001 xing et al", "xing et al 2008", "et al 2008 .", "2008 . the n", ". the n and", "the n and the c", "n and the c terminal", "and the c terminal regions", "the c terminal regions are", "c terminal regions are important", "terminal regions are important for", "regions are important for the", "are important for the recruitment", "important for the recruitment of", "for the recruitment of transcriptional", "the recruitment of transcriptional activator", "recruitment of transcriptional activator and", "of transcriptional activator and repressors", "transcriptional activator and repressors that", "activator and repressors that contribute", "and repressors that contribute to", "repressors that contribute to wnt", "that contribute to wnt target", "target gene expression reviewed", "gene expression reviewed in", "expression reviewed in mosimann", "reviewed in mosimann et al", "mosimann et al 2009", "al 2009 valenta", "2009 valenta et al", "valenta et al 2012", "et al 2012 .", "2012 . the n", ". the n terminal", "the n terminal arm domains", "n terminal arm domains 1", "terminal arm domains 1 4", "arm domains 1 4 recruit", "domains 1 4 recruit the", "1 4 recruit the wnt", "4 recruit the wnt pathway", "recruit the wnt pathway specific", "the wnt pathway specific activators", "wnt pathway specific activators bcl9:pygo", "pathway specific activators bcl9:pygo while", "specific activators bcl9:pygo while the", "activators bcl9:pygo while the c", "bcl9:pygo while the c terminal", "while the c terminal region", "c terminal region r11", "terminal region r11 ctd", "r11 ctd interacts with", "ctd interacts with a", "interacts with a wide range", "with a wide range of", "a wide range of general", "wide range of general transcriptional", "range of general transcriptional activators", "of general transcriptional activators that", "general transcriptional activators that are", "transcriptional activators that are involved", "activators that are involved in", "that are involved in chromatin", "are involved in chromatin remodelling", "involved in chromatin remodelling and", "in chromatin remodelling and transcription", "chromatin remodelling and transcription initiation.", "remodelling and transcription initiation. these", "and transcription initiation. these include", "transcription initiation. these include hats", "initiation. these include hats such", "these include hats such as", "include hats such as p300", "such as p300 cbp", "as p300 cbp and", "p300 cbp and tip60", "cbp and tip60 histone", "and tip60 histone methyltransferases", "tip60 histone methyltransferases such", "histone methyltransferases such as mll1", "methyltransferases such as mll1 and", "such as mll1 and 2", "mll1 and 2 swi/snf", "and 2 swi/snf factors", "2 swi/snf factors brg1", "swi/snf factors brg1 and iswi", "factors brg1 and iswi and", "brg1 and iswi and components", "and iswi and components of", "iswi and components of the", "and components of the paf", "components of the paf complex", "the paf complex reviewed", "paf complex reviewed in", "complex reviewed in mosimann", "2012 . although many", ". although many binding", "although many binding partners have", "many binding partners have been", "binding partners have been identified", "partners have been identified for", "have been identified for the", "been identified for the c", "identified for the c terminal", "for the c terminal region", "the c terminal region of", "c terminal region of beta", "terminal region of beta catenin", "of beta catenin in", "beta catenin in many", "catenin in many cases", "in many cases the timing", "many cases the timing and", "cases the timing and relationship", "the timing and relationship of", "timing and relationship of these", "and relationship of these interactions", "relationship of these interactions and", "of these interactions and indeed", "interactions and indeed the", "and indeed the exact", "indeed the exact complex", "the exact complex composition remains", "exact complex composition remains to", "complex composition remains to be", "composition remains to be elucidated.", "to be elucidated. moreover", "elucidated. moreover because", "moreover because many of", "because many of the interacting", "many of the interacting partners", "of the interacting partners appear", "the interacting partners appear to", "interacting partners appear to bind", "partners appear to bind to", "appear to bind to overlapping", "to bind to overlapping regions", "bind to overlapping regions of", "to overlapping regions of beta", "overlapping regions of beta catenin", "of beta catenin it", "beta catenin it is", "catenin it is unlikely", "it is unlikely that they", "is unlikely that they all", "unlikely that they all bind", "that they all bind simultaneously.", "all bind simultaneously. for", "bind simultaneously. for simplicity", "for simplicity the interactions", "simplicity the interactions have", "the interactions have been depicted", "interactions have been depicted as", "have been depicted as though", "been depicted as though they", "depicted as though they occur", "as though they occur independently", "though they occur independently of", "they occur independently of one", "occur independently of one another", "of one another more", "one another more accurately", "another more accurately they", "more accurately they are likely", "accurately they are likely to", "they are likely to cycle", "are likely to cycle successively", "likely to cycle successively on", "to cycle successively on and", "cycle successively on and off", "successively on and off beta", "on and off beta catenin", "and off beta catenin to", "off beta catenin to promote", "beta catenin to promote an", "catenin to promote an active", "to promote an active chromatin", "promote an active chromatin structure", "active chromatin structure reviewed", "chromatin structure reviewed 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amplification cascade. the", "amplification cascade. the galpha", "cascade. the galpha subunit", "the galpha subunit will", "galpha subunit will eventually", "subunit will eventually hydrolyze", "will eventually hydrolyze the", "eventually hydrolyze the attached", "hydrolyze the attached gtp", "the attached gtp to", "attached gtp to gdp", "gtp to gdp by", "to gdp by its", "gdp by its inherent", "by its inherent enzymatic", "its inherent enzymatic activity", "enzymatic activity allowing", "activity allowing it", "allowing it to reassociate", "it to reassociate with", "to reassociate with gbeta", "reassociate with gbeta gamma", "with gbeta gamma and", "gbeta gamma and start", "gamma and start a", "and start a new", "start a new cycle.", "receptor activated heterotrimeric g proteins", "activated heterotrimeric g proteins consist", "heterotrimeric g proteins consist of", "g proteins consist of the", "proteins consist of the galpha", "consist of the galpha and", "of the galpha and the", "the galpha and the tightly", "galpha and the tightly associated", "and the tightly associated gbeta", "the tightly associated gbeta gamma", "tightly associated gbeta gamma subunits.", "gbeta gamma subunits. when", "gamma subunits. when a", "subunits. when a ligand", "when a ligand binds to", "a ligand binds to a", "ligand binds to a g", "binds to a g protein", "to a g protein coupled", "a g protein coupled receptor", "protein coupled receptor it", "coupled receptor it stabilises", "receptor it stabilises a", "it stabilises a conformation with", "stabilises a conformation with an", "a conformation with an high", "conformation with an high affinity", "with an high affinity for", "an high affinity for the", "high affinity for the g", "affinity for the g protein", "for the g protein bound", "the g protein bound to", "g protein bound to gdp.", "protein bound to gdp. gdp", "bound to gdp. gdp is", "to gdp. gdp is then", "gdp. gdp is then exchanged", "gdp is then exchanged for", "is then exchanged for gtp", "then exchanged for gtp on", "exchanged for gtp on the", "for gtp on the galpha", "gtp on the galpha subunit.", "on the galpha subunit. this", "the galpha subunit. this exchange", "galpha subunit. this exchange triggers", "subunit. this exchange triggers the", "this exchange triggers the dissociation", "exchange triggers the dissociation of", "triggers the dissociation of the", "the dissociation of the galpha", "dissociation of the galpha subunit", "of the galpha subunit from", "the galpha subunit from the", "galpha subunit from the gbeta", "subunit from the gbeta gamma", "from the gbeta gamma dimer", "the gbeta gamma dimer and", "gbeta gamma dimer and the", "gamma dimer and the receptor.", "dimer and the receptor. galpha", "and the receptor. galpha gtp", "the receptor. galpha gtp and", "receptor. galpha gtp and gbeta", "galpha gtp and gbeta gamma", "and gbeta gamma can", "gbeta gamma can then", "gamma can then modulate", "can then modulate different signalling", "then modulate different signalling cascades", "modulate different signalling cascades and", "different signalling cascades and effector", "signalling cascades and effector proteins", "and effector proteins while", "effector proteins while the", "proteins while the receptor", "while the receptor is able", "the receptor is able to", "receptor is able to activate", "is able to activate another", "able to activate another g", "to activate another g protein", "another g protein resulting", "g protein resulting in", "protein resulting in an", "resulting in an amplification cascade.", "in an amplification cascade. the", "an amplification cascade. the galpha", "amplification cascade. the galpha subunit", "cascade. the galpha subunit will", "the galpha subunit will eventually", "galpha subunit will eventually hydrolyze", "subunit will eventually hydrolyze the", "will eventually hydrolyze the attached", "eventually hydrolyze the attached gtp", "hydrolyze the attached gtp to", "the attached gtp to gdp", "attached gtp to gdp by", "gtp to gdp by its", "to gdp by its inherent", "gdp by its inherent enzymatic", "by its inherent enzymatic activity", "inherent enzymatic activity allowing", "enzymatic activity allowing it", "activity allowing it to", "allowing it to reassociate with", "it to reassociate with gbeta", "to reassociate with gbeta gamma", "reassociate with gbeta gamma and", "with gbeta gamma and start", "gbeta gamma and start a", "gamma and start a new", "and start a new cycle." ] }, { "record_id": "GLY_000594_1_183", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2022090", "r hsa", "hsa 2022090", "r hsa 2022090" ] }, { "record_id": "GLY_000594_1_183", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "assembly of", "of collagen", "collagen fibrils", "fibrils and", "and other", "other multimeric", "multimeric structures", "assembly of collagen", "of collagen fibrils", "collagen fibrils and", "fibrils and other", "and other multimeric", "other multimeric structures", "assembly of collagen fibrils", "of collagen fibrils and", "collagen fibrils and other", "fibrils and other multimeric", "and other multimeric structures", "assembly of collagen fibrils and", "of collagen fibrils and other", "collagen fibrils and other multimeric", "fibrils and other multimeric structures", "collagen trimers", "trimers in", "in triple", "triple helical", "helical form", "referred to", "to as", "as procollagen", "procollagen or", "or collagen", "collagen molecules", "are exported", "exported from", "from the", "the er", "er and", "and trafficked", "trafficked through", "through the", "the golgi", "golgi network", "network before", "before secretion", "secretion into", "into the", "the extracellular", "extracellular space.", "space. for", "for fibrillar", "fibrillar collagens", "collagens namely", "namely types", "types i", "xxiv and", "and xxvii", "gordon &", "& hahn", "hahn 2010", "ricard blum", "blum 2011", "secretion is", "is concomitant", "concomitant with", "with processing", "processing of", "of the", "the n", "n and", "and c", "c terminal", "terminal collagen", "collagen propeptides.", "propeptides. these", "these processed", "processed molecules", "molecules are", "are known", "known as", "as tropocollagens", "considered to", "to be", "be the", "the units", "units of", "of higher", "higher order", "order collagen", "collagen structures.", "structures. they", "they form", "form within", "within the", "extracellular space", "space via", "via a", "a process", "process that", "that can", "can proceed", "proceed spontaneously", "but in", "in the", "the cellular", "cellular environment", "environment is", "is regulated", "regulated by", "by many", "many collagen", "collagen binding", "binding proteins", "proteins such", "such as", "as the", "the facit", "fibril associated", "associated collagens", "collagens with", "with interrupted", "interrupted triple", "triple helices", "family collagens", "collagens and", "and small", "small leucine", "leucine rich", "rich proteoglycans", "slrps .", ". the", "the architecture", "architecture formed", "formed ultimately", "ultimately depends", "depends on", "on the", "the collagen", "collagen subtype", "subtype and", "and the", "cellular conditions.", "conditions. structures", "structures include", "include the", "the well", "well known", "known fibrils", "and fibres", "fibres formed", "formed by", "by the", "the major", "major structural", "structural collagens", "collagens type", "type i", "i and", "and ii", "ii plus", "plus several", "several different", "different types", "types of", "of supramolecular", "supramolecular assembly", "bruckner 2010", "2010 .", "the mechanical", "mechanical and", "and physical", "physical properties", "properties of", "of tissues", "tissues depend", "depend on", "the spatial", "spatial arrangement", "arrangement and", "and composition", "composition of", "of these", "these collagen", "collagen containing", "containing structures", "kadler et", "et al.", "al. 1996", "shoulders &", "& raines", "raines 2009", "birk &", "& bruckner", "bruckner 2011", "2011 .

", ".

fibrillar", "fibrillar collagen", "collagen structures", "structures are", "are frequently", "frequently heterotypic", "composed of", "of a", "a major", "major collagen", "collagen type", "type in", "in association", "association with", "with smaller", "smaller amounts", "amounts of", "of other", "other types", "e.g. type", "i collagen", "fibrils are", "are associated", "associated with", "with types", "types iii", "iii and", "and v", "while type", "type ii", "ii fibrils", "fibrils frequently", "frequently contain", "contain types", "types ix", "ix and", "and xi", "wess 2005", "2005 .", ". fibres", "fibres composed", "composed exclusively", "exclusively of", "a single", "single collagen", "type probably", "probably do", "do not", "not exist", "as type", "fibrils require", "require collagens", "collagens v", "v and", "xi respectively", "respectively as", "as nucleators", "al. 2008", "wenstrup et", "al. 2011", "2011 .", "much of", "the structural", "structural understanding", "understanding of", "fibrils has", "has been", "been obtained", "obtained with", "with fibril", "fibril forming", "forming collagens", "particularly type", "but some", "some central", "central features", "features are", "are believed", "believed to", "to apply", "apply to", "to at", "at least", "least the", "the other", "other fibrillar", "collagen subtypes", ". fibril", "fibril diameter", "diameter and", "and length", "length varies", "varies considerably", "depending on", "the tissue", "tissue and", "and collagen", "collagen types", "fang et", "al. 2012", "2012 .", "the reasons", "reasons for", "for this", "this are", "are poorly", "poorly understood", "2005 .

some", ".

some tissues", "tissues such", "as skin", "skin have", "have fibres", "fibres that", "that are", "are approximately", "approximately the", "the same", "same diameter", "diameter while", "while others", "others such", "as tendon", "tendon or", "or cartilage", "cartilage have", "have a", "a bimodal", "bimodal distribution", "distribution of", "of thick", "thick and", "and thin", "thin fibrils.", "fibrils. mature", "mature type", "fibrils in", "in tendon", "tendon are", "are up", "up to", "to 1", "1 cm", "cm in", "in length", "with a", "a diameter", "diameter of", "of approx.", "approx. 500", "500 nm.", "nm. an", "an individual", "individual fibrillar", "collagen triple", "triple helix", "helix is", "is less", "less than", "than 1.5", "1.5 nm", "nm in", "in diameter", "and around", "around 300", "300 nm", "nm long", "molecules must", "must assemble", "assemble to", "to give", "give rise", "rise to", "to the", "the higher", "order fibril", "fibril structure", "process known", "as fibrillogenesis", "prevented by", "the presence", "presence of", "of c", "terminal propeptides", "al. 1987", "1987 .", ". in", "in electron", "electron micrographs", "fibrils have", "a banded", "banded appearance", "due to", "to regular", "regular gaps", "gaps where", "where fewer", "fewer collagen", "molecules overlap", "which occur", "occur because", "because the", "the fibrils", "are aligned", "aligned in", "in a", "a quarter", "quarter stagger", "stagger arrangement", "hodge &", "& petruska", "petruska 1963", "1963 .", ". collagen", "collagen microfibrils", "microfibrils are", "to have", "a quasi", "quasi hexagonal", "hexagonal unit", "unit cell", "with tropocollagen", "tropocollagen arranged", "arranged to", "to form", "form supertwisted", "right handed", "handed microfibrils", "microfibrils that", "that interdigitate", "interdigitate with", "with neighbouring", "neighbouring microfibrils", "leading to", "to a", "a spiral", "spiral like", "like structure", "structure for", "for the", "the mature", "mature collagen", "collagen fibril", "orgel et", "al. 2006", "holmes &", "& kadler", "kadler 2006", "2006 .

neighbouring", ".

neighbouring tropocollagen", "tropocollagen monomers", "monomers interact", "interact with", "with each", "each other", "other and", "and are", "are cross", "cross linked", "linked covalently", "covalently by", "by lysyl", "lysyl oxidase", "al. 2000", "maki 2006", "2006 .", ". mature", "are stabilized", "stabilized by", "oxidase mediated", "mediated cross", "cross links.", "links. hydroxylysyl", "hydroxylysyl pyridinoline", "pyridinoline and", "and lysyl", "lysyl pyridinoline", "pyridinoline cross", "cross links", "links form", "form between", "lysine and", "and hydroxylysine", "hydroxylysine residues", "residues in", "in bone", "bone and", "and cartilage", "eyre et", "al. 1984", "1984 .", ". arginoline", "arginoline cross", "links can", "can form", "form in", "in cartilage", "al. 2010", "mature bovine", "bovine articular", "articular cartilage", "cartilage contains", "contains roughly", "roughly equimolar", "equimolar amounts", "of arginoline", "arginoline and", "and hydroxylysyl", "pyridinoline based", "based on", "on peptide", "peptide yields.", "yields. mature", "in skin", "skin are", "the lysyl", "cross link", "link histidinohydroxylysinonorleucine", "yamauch et", ". due", "the quarter", "quarter staggered", "staggered arrangement", "arrangement of", "molecules in", "a fibril", "telopeptides most", "most often", "often interact", "with the", "the triple", "helix of", "a neighbouring", "neighbouring collagen", "collagen molecule", "molecule in", "the fibril", "except for", "for collagen", "in register", "register staggered", "staggered by", "by 4d", "4d from", "from another", "another collagen", "collagen molecule.", "molecule. fibril", "fibril aggregation", "aggregation in", "in vitro", "vitro can", "can be", "be unipolar", "unipolar or", "or bipolar", "influenced by", "by temperature", "temperature and", "and levels", "levels of", "c proteinase", "suggesting a", "a role", "role for", "propeptides in", "in regulation", "regulation of", "the aggregation", "aggregation process", "1996 .", "in vivo", "molecules at", "at the", "fibril surface", "surface may", "may retain", "retain their", "their n", "n propeptides", "suggesting that", "that this", "this may", "may limit", "limit further", "further accretion", "or alternatively", "alternatively represents", "represents a", "a transient", "transient stage", "stage in", "a model", "model whereby", "whereby fibrils", "fibrils grow", "grow in", "diameter through", "through a", "a cycle", "cycle of", "of deposition", "cleavage and", "and further", "further deposition", "chapman 1989", "1989 .

in", ".

in vivo", "are often", "often composed", "composed from", "from more", "more than", "than one", "one type", "type of", "of collagen.", "collagen. type", "type iii", "iii collagen", "collagen is", "is found", "found associated", "with type", "collagen in", "in dermal", "dermal fibrils", "collagen iii", "iii on", "the periphery", "a regulatory", "regulatory role", "fleischmajer et", "al. 1990", "1990 .", ". type", "type v", "v collagen", "collagen associates", "associates with", "where it", "it may", "limit fibril", "birk et", "white et", "al. 1997", "1997 .", "type ix", "ix associates", "the surface", "surface of", "of narrow", "narrow diameter", "diameter collagen", "collagen ii", "cartilage and", "the cornea", "wu et", "al. 1992", "al. 2004", "2004 .", ". highly", "highly specific", "specific patterns", "patterns of", "of crosslinking", "crosslinking sites", "sites suggest", "suggest that", "that collagen", "collagen ix", "ix functions", "functions in", "in interfibrillar", "interfibrillar networking", "type xii", "xii and", "and xiv", "xiv collagens", "collagens are", "are localized", "localized near", "near the", "of banded", "banded collagen", "collagen i", "i fibrils", "nishiyama et", "al. 1994", "1994 .", ". certain", "certain fibril", "associate with", "where they", "they may", "may serve", "serve to", "to limit", "fibril fusion", "fusion and", "and thereby", "thereby regulate", "regulate fibril", "collagen xv", "a member", "member of", "the multiplexin", "multiplexin family", "is almost", "almost exclusively", "exclusively associated", "the fibrillar", "collagen network", "in very", "very close", "close proximity", "proximity to", "the basement", "basement membrane.", "membrane. in", "in human", "human tissues", "tissues collagen", "xv is", "is seen", "seen linking", "linking banded", "collagen fibers", "fibers subjacent", "subjacent to", "basement membrane", "amenta et", "al. 2005", "type xiv", "xiv collagen", "slrps and", "and discoidin", "discoidin domain", "domain receptors", "receptors also", "also regulate", "regulate fibrillogenesis", "ansorge et", "al. 2009", "kalamajski et", "flynn et", "2010 .

collagen", ".

collagen ix", "ix is", "is cross", "linked to", "are found", "found in", "walchli et", "and type", "watt et", "eyre 2002", "in cartilage.", "cartilage. they", "they are", "are thought", "thought to", "to associate", "associate non", "non covalently", "covalently via", "via their", "their col1/nc1", "col1/nc1 domains", "2002 .", "

some non", "non fibrillar", "collagens form", "form supramolecular", "supramolecular assemblies", "assemblies that", "are distinct", "distinct from", "from typical", "typical fibrils.", "fibrils. collagen", "collagen vii", "vii forms", "forms anchoring", "anchoring fibrils", "of antiparallel", "antiparallel dimers", "dimers that", "that connect", "connect the", "the dermis", "dermis to", "the epidermis", "bruckner tuderman", "tuderman 2009", "2009 .", ". during", "during fibrillogenesis", "the nascent", "nascent type", "type vii", "vii procollagen", "procollagen molecules", "molecules dimerize", "dimerize in", "in an", "an antiparallel", "antiparallel manner.", "manner. the", "the c", "c propeptides", "propeptides are", "are then", "then removed", "removed by", "by bone", "bone morphogenetic", "morphogenetic protein", "protein 1", "rattenholl et", "al. 2002", "the processed", "processed antiparallel", "dimers aggregate", "aggregate laterally.", "laterally. collagens", "collagens viii", "viii and", "and x", "x form", "form hexagonal", "hexagonal networks", "networks and", "collagen vi", "vi forms", "forms beaded", "beaded filament", "blum et", "collagen trimers in", "trimers in triple", "in triple helical", "triple helical form", "form referred", "referred to as", "to as procollagen", "as procollagen or", "procollagen or collagen", "or collagen molecules", "are exported from", "exported from the", "from the er", "the er and", "er and trafficked", "and trafficked through", "trafficked through the", "through the golgi", "the golgi network", "golgi network before", "network before secretion", "before secretion into", "secretion into the", "into the extracellular", "the extracellular space.", "extracellular space. for", "space. for fibrillar", "for fibrillar collagens", "fibrillar collagens namely", "collagens namely types", "namely types i", "i ii", "ii iii", "iii v", "v xi", "xi xxiv", "xxiv and xxvii", "xxvii gordon", "gordon & hahn", "& hahn 2010", "2010 ricard", "ricard blum 2011", "2011 secretion", "secretion is concomitant", "is concomitant with", "concomitant with processing", "with processing of", "processing of the", "of the n", "the n and", "n and c", "and c terminal", "c terminal collagen", "terminal collagen propeptides.", "collagen propeptides. these", "propeptides. these processed", "these processed molecules", "processed molecules are", "molecules are known", "are known as", "known as tropocollagens", "tropocollagens considered", "considered to be", "to be the", "be the units", "the units of", "units of higher", "of higher order", "higher order collagen", "order collagen structures.", "collagen structures. they", "structures. they form", "they form within", "form within the", "within the extracellular", "the extracellular space", "extracellular space via", "space via a", "via a process", "a process that", "process that can", "that can proceed", "can proceed spontaneously", "spontaneously but", "but in the", "in the cellular", "the cellular environment", "cellular environment is", "environment is regulated", "is regulated by", "regulated by many", "by many collagen", "many collagen binding", "collagen binding proteins", "binding proteins such", "proteins such as", "such as the", "as the facit", "facit fibril", "fibril associated collagens", "associated collagens with", "collagens with interrupted", "with interrupted triple", "interrupted triple helices", "helices family", "family collagens and", "collagens and small", "and small leucine", "small leucine rich", "leucine rich proteoglycans", "proteoglycans slrps", "slrps . the", ". the architecture", "the architecture formed", "architecture formed ultimately", "formed ultimately depends", "ultimately depends on", "depends on the", "on the collagen", "the collagen subtype", "collagen subtype and", "subtype and the", "and the cellular", "the cellular conditions.", "cellular conditions. structures", "conditions. structures include", "structures include the", "include the well", "the well known", "well known fibrils", "known fibrils and", "fibrils and fibres", "and fibres formed", "fibres formed by", "formed by the", "by the major", "the major structural", "major structural collagens", "structural collagens type", "collagens type i", "type i and", "i and ii", "and ii plus", "ii plus several", "plus several different", "several different types", "different types of", "types of supramolecular", "of supramolecular assembly", "assembly bruckner", "bruckner 2010 .", "2010 . the", ". the mechanical", "the mechanical and", "mechanical and physical", "and physical properties", "physical properties of", "properties of tissues", "of tissues depend", "tissues depend on", "depend on the", "on the spatial", "the spatial arrangement", "spatial arrangement and", "arrangement and composition", "and composition of", "composition of these", "of these collagen", "these collagen containing", "collagen containing structures", "structures kadler", "kadler et al.", "et al. 1996", "1996 shoulders", "shoulders & raines", "& raines 2009", "2009 birk", "birk & bruckner", "& bruckner 2011", "bruckner 2011 .

", "2011 .

fibrillar", ".

fibrillar collagen", "fibrillar collagen structures", "collagen structures are", "structures are frequently", "are frequently heterotypic", "heterotypic composed", "composed of a", "of a major", "a major collagen", "major collagen type", "collagen type in", "type in association", "in association with", "association with smaller", "with smaller amounts", "smaller amounts of", "amounts of other", "of other types", "types e.g.", "e.g. type i", "type i collagen", "i collagen fibrils", "collagen fibrils are", "fibrils are associated", "are associated with", "associated with types", "with types iii", "types iii and", "iii and v", "v while", "while type ii", "type ii fibrils", "ii fibrils frequently", "fibrils frequently contain", "frequently contain types", "contain types ix", "types ix and", "ix and xi", "xi wess", "wess 2005 .", "2005 . fibres", ". fibres composed", "fibres composed exclusively", "composed exclusively of", "exclusively of a", "of a single", "a single collagen", "single collagen type", "collagen type probably", "type probably do", "probably do not", "do not exist", "exist as", "as type i", "and ii fibrils", "ii fibrils require", "fibrils require collagens", "require collagens v", "collagens v and", "v and xi", "and xi respectively", "xi respectively as", "respectively as nucleators", "nucleators kadler", "et al. 2008", "2008 wenstrup", "wenstrup et al.", "et al. 2011", "al. 2011 .", ". much", "much of the", "of the structural", "the structural understanding", "structural understanding of", "understanding of collagen", "collagen fibrils has", "fibrils has been", "has been obtained", "been obtained with", "obtained with fibril", "with fibril forming", "fibril forming collagens", "collagens particularly", "particularly type i", "i but", "but some central", "some central features", "central features are", "features are believed", "are believed to", "believed to apply", "to apply to", "apply to at", "to at least", "at least the", "least the other", "the other fibrillar", "other fibrillar collagen", "fibrillar collagen subtypes", "subtypes wess", "2005 . fibril", ". fibril diameter", "fibril diameter and", "diameter and length", "and length varies", "length varies considerably", "considerably depending", "depending on the", "on the tissue", "the tissue and", "tissue and collagen", "and collagen types", "types fang", "fang et al.", "et al. 2012", "al. 2012 .", "2012 . the", ". the reasons", "the reasons for", "reasons for this", "for this are", "this are poorly", "are poorly understood", "understood wess", "wess 2005 .

some", "2005 .

some tissues", ".

some tissues such", "tissues such as", "such as skin", "as skin have", "skin have fibres", "have fibres that", "fibres that are", "that are approximately", "are approximately the", "approximately the same", "the same diameter", "same diameter while", "diameter while others", "while others such", "others such as", "such as tendon", "as tendon or", "tendon or cartilage", "or cartilage have", "cartilage have a", "have a bimodal", "a bimodal distribution", "bimodal distribution of", "distribution of thick", "of thick and", "thick and thin", "and thin fibrils.", "thin fibrils. mature", "fibrils. mature type", "mature type i", "collagen fibrils in", "fibrils in tendon", "in tendon are", "tendon are up", "are up to", "up to 1", "to 1 cm", "1 cm in", "cm in length", "length with", "with a diameter", "a diameter of", "diameter of approx.", "of approx. 500", "approx. 500 nm.", "500 nm. an", "nm. an individual", "an individual fibrillar", "individual fibrillar collagen", "fibrillar collagen triple", "collagen triple helix", "triple helix is", "helix is less", "is less than", "less than 1.5", "than 1.5 nm", "1.5 nm in", "nm in diameter", "in diameter and", "diameter and around", "and around 300", "around 300 nm", "300 nm long", "long collagen", "collagen molecules must", "molecules must assemble", "must assemble to", "assemble to give", "to give rise", "give rise to", "rise to the", "to the higher", "the higher order", "higher order fibril", "order fibril structure", "structure a", "a process known", "process known as", "known as fibrillogenesis", "fibrillogenesis prevented", "prevented by the", "by the presence", "the presence of", "presence of c", "of c terminal", "c terminal propeptides", "propeptides kadler", "et al. 1987", "al. 1987 .", "1987 . in", ". in electron", "in electron micrographs", "micrographs fibrils", "fibrils have a", "have a banded", "a banded appearance", "appearance due", "due to regular", "to regular gaps", "regular gaps where", "gaps where fewer", "where fewer collagen", "fewer collagen molecules", "collagen molecules overlap", "overlap which", "which occur because", "occur because the", "because the fibrils", "the fibrils are", "fibrils are aligned", "are aligned in", "aligned in a", "in a quarter", "a quarter stagger", "quarter stagger arrangement", "arrangement hodge", "hodge & petruska", "& petruska 1963", "petruska 1963 .", "1963 . collagen", ". collagen microfibrils", "collagen microfibrils are", "microfibrils are believed", "believed to have", "to have a", "have a quasi", "a quasi hexagonal", "quasi hexagonal unit", "hexagonal unit cell", "cell with", "with tropocollagen arranged", "tropocollagen arranged to", "arranged to form", "to form supertwisted", "supertwisted right", "right handed microfibrils", "handed microfibrils that", "microfibrils that interdigitate", "that interdigitate with", "interdigitate with neighbouring", "with neighbouring microfibrils", "microfibrils leading", "leading to a", "to a spiral", "a spiral like", "spiral like structure", "like structure for", "structure for the", "for the mature", "the mature collagen", "mature collagen fibril", "fibril orgel", "orgel et al.", "et al. 2006", "2006 holmes", "holmes & kadler", "& kadler 2006", "kadler 2006 .

neighbouring", "2006 .

neighbouring tropocollagen", ".

neighbouring tropocollagen monomers", "tropocollagen monomers interact", "monomers interact with", "interact with each", "with each other", "each other and", "other and are", "and are cross", "are cross linked", "cross linked covalently", "linked covalently by", "covalently by lysyl", "by lysyl oxidase", "oxidase orgel", "et al. 2000", "2000 maki", "maki 2006 .", "2006 . mature", ". mature collagen", "mature collagen fibrils", "fibrils are stabilized", "are stabilized by", "stabilized by lysyl", "lysyl oxidase mediated", "oxidase mediated cross", "mediated cross links.", "cross links. hydroxylysyl", "links. hydroxylysyl pyridinoline", "hydroxylysyl pyridinoline and", "pyridinoline and lysyl", "and lysyl pyridinoline", "lysyl pyridinoline cross", "pyridinoline cross links", "cross links form", "links form between", "between hydroxy", "hydroxy lysine", "lysine and hydroxylysine", "and hydroxylysine residues", "hydroxylysine residues in", "residues in bone", "in bone and", "bone and cartilage", "cartilage eyre", "eyre et al.", "et al. 1984", "al. 1984 .", "1984 . arginoline", ". arginoline cross", "arginoline cross links", "cross links can", "links can form", "can form in", "form in cartilage", "et al. 2010", "mature bovine articular", "bovine articular cartilage", "articular cartilage contains", "cartilage contains roughly", "contains roughly equimolar", "roughly equimolar amounts", "equimolar amounts of", "amounts of arginoline", "of arginoline and", "arginoline and hydroxylysyl", "and hydroxylysyl pyridinoline", "hydroxylysyl pyridinoline based", "pyridinoline based on", "based on peptide", "on peptide yields.", "peptide yields. mature", "yields. mature collagen", "fibrils in skin", "in skin are", "skin are stabilized", "stabilized by the", "by the lysyl", "the lysyl oxidase", "mediated cross link", "cross link histidinohydroxylysinonorleucine", "histidinohydroxylysinonorleucine yamauch", "yamauch et al.", "1987 . due", ". due to", "due to the", "to the quarter", "the quarter staggered", "quarter staggered arrangement", "staggered arrangement of", "arrangement of collagen", "of collagen molecules", "collagen molecules in", "molecules in a", "in a fibril", "fibril telopeptides", "telopeptides most often", "most often interact", "often interact with", "interact with the", "with the triple", "the triple helix", "triple helix of", "helix of a", "of a neighbouring", "a neighbouring collagen", "neighbouring collagen molecule", "collagen molecule in", "molecule in the", "in the fibril", "fibril except", "except for collagen", "for collagen molecules", "molecules in register", "in register staggered", "register staggered by", "staggered by 4d", "by 4d from", "4d from another", "from another collagen", "another collagen molecule.", "collagen molecule. fibril", "molecule. fibril aggregation", "fibril aggregation in", "aggregation in vitro", "in vitro can", "vitro can be", "can be unipolar", "be unipolar or", "unipolar or bipolar", "bipolar influenced", "influenced by temperature", "by temperature and", "temperature and levels", "and levels of", "levels of c", "of c proteinase", "proteinase suggesting", "suggesting a role", "a role for", "role for the", "for the n", "propeptides in regulation", "in regulation of", "regulation of the", "of the aggregation", "the aggregation process", "process kadler", "al. 1996 .", "1996 . in", ". in vivo", "vivo collagen", "collagen molecules at", "molecules at the", "at the fibril", "the fibril surface", "fibril surface may", "surface may retain", "may retain their", "retain their n", "their n propeptides", "propeptides suggesting", "suggesting that this", "that this may", "this may limit", "may limit further", "limit further accretion", "accretion or", "or alternatively represents", "alternatively represents a", "represents a transient", "a transient stage", "transient stage in", "stage in a", "in a model", "a model whereby", "model whereby fibrils", "whereby fibrils grow", "fibrils grow in", "grow in diameter", "in diameter through", "diameter through a", "through a cycle", "a cycle of", "cycle of deposition", "deposition cleavage", "cleavage and further", "and further deposition", "deposition chapman", "chapman 1989 .

in", "1989 .

in vivo", "vivo fibrils", "fibrils are often", "are often composed", "often composed from", "composed from more", "from more than", "more than one", "than one type", "one type of", "type of collagen.", "of collagen. type", "collagen. type iii", "type iii collagen", "iii collagen is", "collagen is found", "is found associated", "found associated with", "associated with type", "with type i", "i collagen in", "collagen in dermal", "in dermal fibrils", "fibrils with", "with the collagen", "the collagen iii", "collagen iii on", "iii on the", "on the periphery", "periphery suggesting", "suggesting a regulatory", "a regulatory role", "role fleischmajer", "fleischmajer et al.", "et al. 1990", "al. 1990 .", "1990 . type", ". type v", "type v collagen", "v collagen associates", "collagen associates with", "associates with type", "fibrils where", "where it may", "it may limit", "may limit fibril", "limit fibril diameter", "diameter birk", "birk et al.", "1990 white", "white et al.", "et al. 1997", "al. 1997 .", "1997 . type", ". type ix", "type ix associates", "ix associates with", "associates with the", "with the surface", "the surface of", "surface of narrow", "of narrow diameter", "narrow diameter collagen", "diameter collagen ii", "collagen ii fibrils", "ii fibrils in", "fibrils in cartilage", "in cartilage and", "cartilage and the", "and the cornea", "cornea wu", "wu et al.", "et al. 1992", "1992 eyre", "et al. 2004", "al. 2004 .", "2004 . highly", ". highly specific", "highly specific patterns", "specific patterns of", "patterns of crosslinking", "of crosslinking sites", "crosslinking sites suggest", "sites suggest that", "suggest that collagen", "that collagen ix", "collagen ix functions", "ix functions in", "functions in interfibrillar", "in interfibrillar networking", "networking wess", "2005 . type", ". type xii", "type xii and", "xii and xiv", "and xiv collagens", "xiv collagens are", "collagens are localized", "are localized near", "localized near the", "near the surface", "surface of banded", "of banded collagen", "banded collagen i", "collagen i fibrils", "fibrils nishiyama", "nishiyama et al.", "et al. 1994", "al. 1994 .", "1994 . certain", ". certain fibril", "certain fibril associated", "helices facits", "facits associate", "associate with the", "surface of collagen", "where they may", "they may serve", "may serve to", "serve to limit", "to limit fibril", "limit fibril fusion", "fibril fusion and", "fusion and thereby", "and thereby regulate", "thereby regulate fibril", "regulate fibril diameter", "diameter gordon", "hahn 2010 .", "2010 . collagen", ". collagen xv", "xv a", "a member of", "member of the", "of the multiplexin", "the multiplexin family", "family is", "is almost exclusively", "almost exclusively associated", "exclusively associated with", "associated with the", "with the fibrillar", "the fibrillar collagen", "fibrillar collagen network", "network in", "in very close", "very close proximity", "close proximity to", "proximity to the", "to the basement", "the basement membrane.", "basement membrane. in", "membrane. in human", "in human tissues", "human tissues collagen", "tissues collagen xv", "collagen xv is", "xv is seen", "is seen linking", "seen linking banded", "linking banded collagen", "banded collagen fibers", "collagen fibers subjacent", "fibers subjacent to", "subjacent to the", "the basement membrane", "membrane amenta", "amenta et al.", "et al. 2005", "al. 2005 .", ". type xiv", "type xiv collagen", "collagen slrps", "slrps and discoidin", "and discoidin domain", "discoidin domain receptors", "domain receptors also", "receptors also regulate", "also regulate fibrillogenesis", "fibrillogenesis ansorge", "ansorge et al.", "et al. 2009", "2009 kalamajski", "kalamajski et al.", "2010 flynn", "flynn et al.", "al. 2010 .

collagen", "2010 .

collagen ix", ".

collagen ix is", "ix is cross", "is cross linked", "cross linked to", "linked to the", "to the surface", "of collagen type", "collagen type ii", "fibrils eyre", "1987 . type", "collagens are found", "are found in", "found in association", "association with type", "i walchli", "walchli et al.", "1994 and", "and type ii", "ii watt", "watt et al.", "2002 fibrils", "fibrils in cartilage.", "in cartilage. they", "cartilage. they are", "they are thought", "are thought to", "thought to associate", "to associate non", "associate non covalently", "non covalently via", "covalently via their", "via their col1/nc1", "their col1/nc1 domains", "domains watt", "eyre 2002 .", ".

some", "

some non fibrillar", "non fibrillar collagens", "fibrillar collagens form", "collagens form supramolecular", "form supramolecular assemblies", "supramolecular assemblies that", "assemblies that are", "that are distinct", "are distinct from", "distinct from typical", "from typical fibrils.", "typical fibrils. collagen", "fibrils. collagen vii", "collagen vii forms", "vii forms anchoring", "forms anchoring fibrils", "fibrils composed", "composed of antiparallel", "of antiparallel dimers", "antiparallel dimers that", "dimers that connect", "that connect the", "connect the dermis", "the dermis to", "dermis to the", "to the epidermis", "epidermis bruckner", "bruckner tuderman 2009", "tuderman 2009 .", "2009 . during", ". during fibrillogenesis", "fibrillogenesis the", "the nascent type", "nascent type vii", "type vii procollagen", "vii procollagen molecules", "procollagen molecules dimerize", "molecules dimerize in", "dimerize in an", "in an antiparallel", "an antiparallel manner.", "antiparallel manner. the", "manner. the c", "the c propeptides", "c propeptides are", "propeptides are then", "are then removed", "then removed by", "removed by bone", "by bone morphogenetic", "bone morphogenetic protein", "morphogenetic protein 1", "1 rattenholl", "rattenholl et al.", "et al. 2002", "2002 and", "and the processed", "the processed antiparallel", "processed antiparallel dimers", "antiparallel dimers aggregate", "dimers aggregate laterally.", "aggregate laterally. collagens", "laterally. collagens viii", "collagens viii and", "viii and x", "and x form", "x form hexagonal", "form hexagonal networks", "hexagonal networks and", "networks and collagen", "and collagen vi", "collagen vi forms", "vi forms beaded", "forms beaded filament", "filament gordon", "ricard blum et", "blum et al.", "collagen trimers in triple", "trimers in triple helical", "in triple helical form", "helical form referred", "form referred to", "referred to as procollagen", "to as procollagen or", "as procollagen or collagen", "procollagen or collagen molecules", "collagen molecules are", "molecules are exported", "are exported from the", "exported from the er", "from the er and", "the er and trafficked", "er and trafficked through", "and trafficked through the", "trafficked through the golgi", "through the golgi network", "the golgi network before", "golgi network before secretion", "network before secretion into", "before secretion into the", "secretion into the extracellular", "into the extracellular space.", "the extracellular space. for", "extracellular space. for fibrillar", "space. for fibrillar collagens", "for fibrillar collagens namely", "fibrillar collagens namely types", "collagens namely types i", "types i ii", "xi xxiv and", "and xxvii gordon", "xxvii gordon &", "gordon & hahn 2010", "hahn 2010 ricard", "2010 ricard blum", "blum 2011 secretion", "2011 secretion is", "secretion is concomitant with", "is concomitant with processing", "concomitant with processing of", "with processing of the", "processing of the n", "of the n and", "the n and c", "n and c terminal", "and c terminal collagen", "c terminal collagen propeptides.", "terminal collagen propeptides. these", "collagen propeptides. these processed", "propeptides. these processed molecules", "these processed molecules are", "processed molecules are known", "molecules are known as", "are known as tropocollagens", "as tropocollagens considered", "tropocollagens considered to", "considered to be the", "to be the units", "be the units of", "the units of higher", "units of higher order", "of higher order collagen", "higher order collagen structures.", "order collagen structures. they", "collagen structures. they form", "structures. they form within", "they form within the", "form within the extracellular", "within the extracellular space", "the extracellular space via", "extracellular space via a", "space via a process", "via a process that", "a process that can", "process that can proceed", "that can proceed spontaneously", "proceed spontaneously but", "spontaneously but in", "but in the cellular", "in the cellular environment", "the cellular environment is", "cellular environment is regulated", "environment is regulated by", "is regulated by many", "regulated by many collagen", "by many collagen binding", "many collagen binding proteins", "collagen binding proteins such", "binding proteins such as", "proteins such as the", "such as the facit", "the facit fibril", "facit fibril associated", "fibril associated collagens with", "associated collagens with interrupted", "collagens with interrupted triple", "with interrupted triple helices", "triple helices family", "helices family collagens", "family collagens and small", "collagens and small leucine", "and small leucine rich", "small leucine rich proteoglycans", "rich proteoglycans slrps", "proteoglycans slrps .", "slrps . the architecture", ". the architecture formed", "the architecture formed ultimately", "architecture formed ultimately depends", "formed ultimately depends on", "ultimately depends on the", "depends on the collagen", "on the collagen subtype", "the collagen subtype and", "collagen subtype and the", "subtype and the cellular", "and the cellular conditions.", "the cellular conditions. structures", "cellular conditions. structures include", "conditions. structures include the", "structures include the well", "include the well known", "the well known fibrils", "well known fibrils and", "known fibrils and fibres", "fibrils and fibres formed", "and fibres formed by", "fibres formed by the", "formed by the major", "by the major structural", "the major structural collagens", "major structural collagens type", "structural collagens type i", "collagens type i and", "type i and ii", "i and ii plus", "and ii plus several", "ii plus several different", "plus several different types", "several different types of", "different types of supramolecular", "types of supramolecular assembly", "supramolecular assembly bruckner", "assembly bruckner 2010", "bruckner 2010 . the", "2010 . the mechanical", ". the mechanical and", "the mechanical and physical", "mechanical and physical properties", "and physical properties of", "physical properties of tissues", "properties of tissues depend", "of tissues depend on", "tissues depend on the", "depend on the spatial", "on the spatial arrangement", "the spatial arrangement and", "spatial arrangement and composition", "arrangement and composition of", "and composition of these", "composition of these collagen", "of these collagen containing", "these collagen containing structures", "containing structures kadler", "structures kadler et", "kadler et al. 1996", "al. 1996 shoulders", "1996 shoulders &", "shoulders & raines 2009", "raines 2009 birk", "2009 birk &", "birk & bruckner 2011", "& bruckner 2011 .

", "bruckner 2011 .

fibrillar", "2011 .

fibrillar collagen", ".

fibrillar collagen structures", "fibrillar collagen structures are", "collagen structures are frequently", "structures are frequently heterotypic", "frequently heterotypic composed", "heterotypic composed of", "composed of a major", "of a major collagen", "a major collagen type", "major collagen type in", "collagen type in association", "type in association with", "in association with smaller", "association with smaller amounts", "with smaller amounts of", "smaller amounts of other", "amounts of other types", "other types e.g.", "types e.g. type", "e.g. type i collagen", "type i collagen fibrils", "i collagen fibrils are", "collagen fibrils are associated", "fibrils are associated with", "are associated with types", "associated with types iii", "with types iii and", "types iii and v", "and v while", "v while type", "while type ii fibrils", "type ii fibrils frequently", "ii fibrils frequently contain", "fibrils frequently contain types", "frequently contain types ix", "contain types ix and", "types ix and xi", "and xi wess", "xi wess 2005", "wess 2005 . fibres", "2005 . fibres composed", ". fibres composed exclusively", "fibres composed exclusively of", "composed exclusively of a", "exclusively of a single", "of a single collagen", "a single collagen type", "single collagen type probably", "collagen type probably do", "type probably do not", "probably do not exist", "not exist as", "exist as type", "as type i and", "i and ii fibrils", "and ii fibrils require", "ii fibrils require collagens", "fibrils require collagens v", "require collagens v and", "collagens v and xi", "v and xi respectively", "and xi respectively as", "xi respectively as nucleators", "as nucleators kadler", "nucleators kadler et", "kadler et al. 2008", "al. 2008 wenstrup", "2008 wenstrup et", "wenstrup et al. 2011", "et al. 2011 .", "2011 . much", ". much of", "much of the structural", "of the structural understanding", "the structural understanding of", "structural understanding of collagen", "understanding of collagen fibrils", "of collagen fibrils has", "collagen fibrils has been", "fibrils has been obtained", "has been obtained with", "been obtained with fibril", "obtained with fibril forming", "with fibril forming collagens", "forming collagens particularly", "collagens particularly type", "type i but", "i but some", "but some central features", "some central features are", "central features are believed", "features are believed to", "are believed to apply", "believed to apply to", "to apply to at", "apply to at least", "to at least the", "at least the other", "least the other fibrillar", "the other fibrillar collagen", "other fibrillar collagen subtypes", "collagen subtypes wess", "subtypes wess 2005", "wess 2005 . fibril", "2005 . fibril diameter", ". fibril diameter and", "fibril diameter and length", "diameter and length varies", "and length varies considerably", "varies considerably depending", "considerably depending on", "depending on the tissue", "on the tissue and", "the tissue and collagen", "tissue and collagen types", "collagen types fang", "types fang et", "fang et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the reasons", ". the reasons for", "the reasons for this", "reasons for this are", "for this are poorly", "this are poorly understood", "poorly understood wess", "understood wess 2005", "wess 2005 .

some tissues", "2005 .

some tissues such", ".

some tissues such as", "tissues such as skin", "such as skin have", "as skin have fibres", "skin have fibres that", "have fibres that are", "fibres that are approximately", "that are approximately the", "are approximately the same", "approximately the same diameter", "the same diameter while", "same diameter while others", "diameter while others such", "while others such as", "others such as tendon", "such as tendon or", "as tendon or cartilage", "tendon or cartilage have", "or cartilage have a", "cartilage have a bimodal", "have a bimodal distribution", "a bimodal distribution of", "bimodal distribution of thick", "distribution of thick and", "of thick and thin", "thick and thin fibrils.", "and thin fibrils. mature", "thin fibrils. mature type", "fibrils. mature type i", "mature type i collagen", "i collagen fibrils in", "collagen fibrils in tendon", "fibrils in tendon are", "in tendon are up", "tendon are up to", "are up to 1", "up to 1 cm", "to 1 cm in", "1 cm in length", "in length with", "length with a", "with a diameter of", "a diameter of approx.", "diameter of approx. 500", "of approx. 500 nm.", "approx. 500 nm. an", "500 nm. an individual", "nm. an individual fibrillar", "an individual fibrillar collagen", "individual fibrillar collagen triple", "fibrillar collagen triple helix", "collagen triple helix is", "triple helix is less", "helix is less than", "is less than 1.5", "less than 1.5 nm", "than 1.5 nm in", "1.5 nm in diameter", "nm in diameter and", "in diameter and around", "diameter and around 300", "and around 300 nm", "around 300 nm long", "nm long collagen", "long collagen molecules", "collagen molecules must assemble", "molecules must assemble to", "must assemble to give", "assemble to give rise", "to give rise to", "give rise to the", "rise to the higher", "to the higher order", "the higher order fibril", "higher order fibril structure", "fibril structure a", "structure a process", "a process known as", "process known as fibrillogenesis", "as fibrillogenesis prevented", "fibrillogenesis prevented by", "prevented by the presence", "by the presence of", "the presence of c", "presence of c terminal", "of c terminal propeptides", "terminal propeptides kadler", "propeptides kadler et", "kadler et al. 1987", "et al. 1987 .", "al. 1987 . in", "1987 . in electron", ". in electron micrographs", "electron micrographs fibrils", "micrographs fibrils have", "fibrils have a banded", "have a banded appearance", "banded appearance due", "appearance due to", "due to regular gaps", "to regular gaps where", "regular gaps where fewer", "gaps where fewer collagen", "where fewer collagen molecules", "fewer collagen molecules overlap", "molecules overlap which", "overlap which occur", "which occur because the", "occur because the fibrils", "because the fibrils are", "the fibrils are aligned", "fibrils are aligned in", "are aligned in a", "aligned in a quarter", "in a quarter stagger", "a quarter stagger arrangement", "stagger arrangement hodge", "arrangement hodge &", "hodge & petruska 1963", "& petruska 1963 .", "petruska 1963 . collagen", "1963 . collagen microfibrils", ". collagen microfibrils are", "collagen microfibrils are believed", "microfibrils are believed to", "are believed to have", "believed to have a", "to have a quasi", "have a quasi hexagonal", "a quasi hexagonal unit", "quasi hexagonal unit cell", "unit cell with", "cell with tropocollagen", "with tropocollagen arranged to", "tropocollagen arranged to form", "arranged to form supertwisted", "form supertwisted right", "supertwisted right handed", "right handed microfibrils that", "handed microfibrils that interdigitate", "microfibrils that interdigitate with", "that interdigitate with neighbouring", "interdigitate with neighbouring microfibrils", "neighbouring microfibrils leading", "microfibrils leading to", "leading to a spiral", "to a spiral like", "a spiral like structure", "spiral like structure for", "like structure for the", "structure for the mature", "for the mature collagen", "the mature collagen fibril", "collagen fibril orgel", "fibril orgel et", "orgel et al. 2006", "al. 2006 holmes", "2006 holmes &", "holmes & kadler 2006", "& kadler 2006 .

neighbouring", "kadler 2006 .

neighbouring tropocollagen", "2006 .

neighbouring tropocollagen monomers", ".

neighbouring tropocollagen monomers interact", "tropocollagen monomers interact with", "monomers interact with each", "interact with each other", "with each other and", "each other and are", "other and are cross", "and are cross linked", "are cross linked covalently", "cross linked covalently by", "linked covalently by lysyl", "covalently by lysyl oxidase", "lysyl oxidase orgel", "oxidase orgel et", "orgel et al. 2000", "al. 2000 maki", "2000 maki 2006", "maki 2006 . mature", "2006 . mature collagen", ". mature collagen fibrils", "mature collagen fibrils are", "collagen fibrils are stabilized", "fibrils are stabilized by", "are stabilized by lysyl", "stabilized by lysyl oxidase", "by lysyl oxidase mediated", "lysyl oxidase mediated cross", "oxidase mediated cross links.", "mediated cross links. hydroxylysyl", "cross links. hydroxylysyl pyridinoline", "links. hydroxylysyl pyridinoline and", "hydroxylysyl pyridinoline and lysyl", "pyridinoline and lysyl pyridinoline", "and lysyl pyridinoline cross", "lysyl pyridinoline cross links", "pyridinoline cross links form", "cross links form between", "form between hydroxy", "hydroxy lysine and", "lysine and hydroxylysine residues", "and hydroxylysine residues in", "hydroxylysine residues in bone", "residues in bone and", "in bone and cartilage", "and cartilage eyre", "cartilage eyre et", "eyre et al. 1984", "et al. 1984 .", "al. 1984 . arginoline", "1984 . arginoline cross", ". arginoline cross links", "arginoline cross links can", "cross links can form", "links can form in", "can form in cartilage", "in cartilage eyre", "eyre et al. 2010", "2010 mature", "mature bovine articular cartilage", "bovine articular cartilage contains", "articular cartilage contains roughly", "cartilage contains roughly equimolar", "contains roughly equimolar amounts", "roughly equimolar amounts of", "equimolar amounts of arginoline", "amounts of arginoline and", "of arginoline and hydroxylysyl", "arginoline and hydroxylysyl pyridinoline", "and hydroxylysyl pyridinoline based", "hydroxylysyl pyridinoline based on", "pyridinoline based on peptide", "based on peptide yields.", "on peptide yields. mature", "peptide yields. mature collagen", "yields. mature collagen fibrils", "mature collagen fibrils in", "collagen fibrils in skin", "fibrils in skin are", "in skin are stabilized", "skin are stabilized by", "are stabilized by the", "stabilized by the lysyl", "by the lysyl oxidase", "the lysyl oxidase mediated", "oxidase mediated cross link", "mediated cross link histidinohydroxylysinonorleucine", "link histidinohydroxylysinonorleucine yamauch", "histidinohydroxylysinonorleucine yamauch et", "yamauch et al. 1987", "al. 1987 . due", "1987 . due to", ". due to the", "due to the quarter", "to the quarter staggered", "the quarter staggered arrangement", "quarter staggered arrangement of", "staggered arrangement of collagen", "arrangement of collagen molecules", "of collagen molecules in", "collagen molecules in a", "molecules in a fibril", "a fibril telopeptides", "fibril telopeptides most", "telopeptides most often interact", "most often interact with", "often interact with the", "interact with the triple", "with the triple helix", "the triple helix of", "triple helix of a", "helix of a neighbouring", "of a neighbouring collagen", "a neighbouring collagen molecule", "neighbouring collagen molecule in", "collagen molecule in the", "molecule in the fibril", "the fibril except", "fibril except for", "except for collagen molecules", "for collagen molecules in", "collagen molecules in register", "molecules in register staggered", "in register staggered by", "register staggered by 4d", "staggered by 4d from", "by 4d from another", "4d from another collagen", "from another collagen molecule.", "another collagen molecule. fibril", "collagen molecule. fibril aggregation", "molecule. fibril aggregation in", "fibril aggregation in vitro", "aggregation in vitro can", "in vitro can be", "vitro can be unipolar", "can be unipolar or", "be unipolar or bipolar", "or bipolar influenced", "bipolar influenced by", "influenced by temperature and", "by temperature and levels", "temperature and levels of", "and levels of c", "levels of c proteinase", "c proteinase suggesting", "proteinase suggesting a", "suggesting a role for", "a role for the", "role for the n", "and c propeptides", "c propeptides in", "propeptides in regulation of", "in regulation of the", "regulation of the aggregation", "of the aggregation process", "aggregation process kadler", "process kadler et", "et al. 1996 .", "al. 1996 . in", "1996 . in vivo", "in vivo collagen", "vivo collagen molecules", "collagen molecules at the", "molecules at the fibril", "at the fibril surface", "the fibril surface may", "fibril surface may retain", "surface may retain their", "may retain their n", "retain their n propeptides", "n propeptides suggesting", "propeptides suggesting that", "suggesting that this may", "that this may limit", "this may limit further", "may limit further accretion", "further accretion or", "accretion or alternatively", "or alternatively represents a", "alternatively represents a transient", "represents a transient stage", "a transient stage in", "transient stage in a", "stage in a model", "in a model whereby", "a model whereby fibrils", "model whereby fibrils grow", "whereby fibrils grow in", "fibrils grow in diameter", "grow in diameter through", "in diameter through a", "diameter through a cycle", "through a cycle of", "a cycle of deposition", "of deposition cleavage", "deposition cleavage and", "cleavage and further deposition", "further deposition chapman", "deposition chapman 1989", "chapman 1989 .

in vivo", ".

in vivo fibrils", "vivo fibrils are", "fibrils are often composed", "are often composed from", "often composed from more", "composed from more than", "from more than one", "more than one type", "than one type of", "one type of collagen.", "type of collagen. type", "of collagen. type iii", "collagen. type iii collagen", "type iii collagen is", "iii collagen is found", "collagen is found associated", "is found associated with", "found associated with type", "associated with type i", "with type i collagen", "type i collagen in", "i collagen in dermal", "collagen in dermal fibrils", "dermal fibrils with", "fibrils with the", "with the collagen iii", "the collagen iii on", "collagen iii on the", "iii on the periphery", "the periphery suggesting", "periphery suggesting a", "suggesting a regulatory role", "regulatory role fleischmajer", "role fleischmajer et", "fleischmajer et al. 1990", "et al. 1990 .", "al. 1990 . type", "1990 . type v", ". type v collagen", "type v collagen associates", "v collagen associates with", "collagen associates with type", "associates with type i", "collagen fibrils where", "fibrils where it", "where it may limit", "it may limit fibril", "may limit fibril diameter", "fibril diameter birk", "diameter birk et", "birk et al. 1990", "al. 1990 white", "1990 white et", "white et al. 1997", "et al. 1997 .", "al. 1997 . type", "1997 . type ix", ". type ix associates", "type ix associates with", "ix associates with the", "associates with the surface", "with the surface of", "the surface of narrow", "surface of narrow diameter", "of narrow diameter collagen", "narrow diameter collagen ii", "diameter collagen ii fibrils", "collagen ii fibrils in", "ii fibrils in cartilage", "fibrils in cartilage and", "in cartilage and the", "cartilage and the cornea", "the cornea wu", "cornea wu et", "wu et al. 1992", "al. 1992 eyre", "1992 eyre et", "eyre et al. 2004", "et al. 2004 .", "al. 2004 . highly", "2004 . highly specific", ". highly specific patterns", "highly specific patterns of", "specific patterns of crosslinking", "patterns of crosslinking sites", "of crosslinking sites suggest", "crosslinking sites suggest that", "sites suggest that collagen", "suggest that collagen ix", "that collagen ix functions", "collagen ix functions in", "ix functions in interfibrillar", "functions in interfibrillar networking", "interfibrillar networking wess", "networking wess 2005", "wess 2005 . type", "2005 . type xii", ". type xii and", "type xii and xiv", "xii and xiv collagens", "and xiv collagens are", "xiv collagens are localized", "collagens are localized near", "are localized near the", "localized near the surface", "near the surface of", "the surface of banded", "surface of banded collagen", "of banded collagen i", "banded collagen i fibrils", "i fibrils nishiyama", "fibrils nishiyama et", "nishiyama et al. 1994", "et al. 1994 .", "al. 1994 . certain", "1994 . certain fibril", ". certain fibril associated", "certain fibril associated collagens", "triple helices facits", "facits associate with", "associate with the surface", "the surface of collagen", "surface of collagen fibrils", "fibrils where they", "where they may serve", "they may serve to", "may serve to limit", "serve to limit fibril", "to limit fibril fusion", "limit fibril fusion and", "fibril fusion and thereby", "fusion and thereby regulate", "and thereby regulate fibril", "thereby regulate fibril diameter", "fibril diameter gordon", "diameter gordon &", "& hahn 2010 .", "hahn 2010 . collagen", "2010 . collagen xv", "collagen xv a", "xv a member", "a member of the", "member of the multiplexin", "of the multiplexin family", "multiplexin family is", "family is almost", "is almost exclusively associated", "almost exclusively associated with", "exclusively associated with the", "associated with the fibrillar", "with the fibrillar collagen", "the fibrillar collagen network", "collagen network in", "network in very", "in very close proximity", "very close proximity to", "close proximity to the", "proximity to the basement", "to the basement membrane.", "the basement membrane. in", "basement membrane. in human", "membrane. in human tissues", "in human tissues collagen", "human tissues collagen xv", "tissues collagen xv is", "collagen xv is seen", "xv is seen linking", "is seen linking banded", "seen linking banded collagen", "linking banded collagen fibers", "banded collagen fibers subjacent", "collagen fibers subjacent to", "fibers subjacent to the", "subjacent to the basement", "to the basement membrane", "basement membrane amenta", "membrane amenta et", "amenta et al. 2005", "et al. 2005 .", "al. 2005 . type", "2005 . type xiv", ". type xiv collagen", "xiv collagen slrps", "collagen slrps and", "slrps and discoidin domain", "and discoidin domain receptors", "discoidin domain receptors also", "domain receptors also regulate", "receptors also regulate fibrillogenesis", "regulate fibrillogenesis ansorge", "fibrillogenesis ansorge et", "ansorge et al. 2009", "al. 2009 kalamajski", "2009 kalamajski et", "kalamajski et al. 2010", "al. 2010 flynn", "2010 flynn et", "flynn et al. 2010", "et al. 2010 .

collagen", "al. 2010 .

collagen ix", "2010 .

collagen ix is", ".

collagen ix is cross", "ix is cross linked", "is cross linked to", "cross linked to the", "linked to the surface", "to the surface of", "surface of collagen type", "of collagen type ii", "collagen type ii fibrils", "ii fibrils eyre", "fibrils eyre et", "eyre et al. 1987", "al. 1987 . type", "1987 . type xii", "xiv collagens are found", "collagens are found in", "are found in association", "found in association with", "in association with type", "association with type i", "type i walchli", "i walchli et", "walchli et al. 1994", "al. 1994 and", "1994 and type", "type ii watt", "ii watt et", "watt et al. 1992", "1992 eyre 2002", "eyre 2002 fibrils", "2002 fibrils in", "fibrils in cartilage. they", "in cartilage. they are", "cartilage. they are thought", "they are thought to", "are thought to associate", "thought to associate non", "to associate non covalently", "associate non covalently via", "non covalently via their", "covalently via their col1/nc1", "via their col1/nc1 domains", "col1/nc1 domains watt", "domains watt et", "2002 .

some", ".

some non", "

some non fibrillar collagens", "non fibrillar collagens form", "fibrillar collagens form supramolecular", "collagens form supramolecular assemblies", "form supramolecular assemblies that", "supramolecular assemblies that are", "assemblies that are distinct", "that are distinct from", "are distinct from typical", "distinct from typical fibrils.", "from typical fibrils. collagen", "typical fibrils. collagen vii", "fibrils. collagen vii forms", "collagen vii forms anchoring", "vii forms anchoring fibrils", "anchoring fibrils composed", "fibrils composed of", "composed of antiparallel dimers", "of antiparallel dimers that", "antiparallel dimers that connect", "dimers that connect the", "that connect the dermis", "connect the dermis to", "the dermis to the", "dermis to the epidermis", "the epidermis bruckner", "epidermis bruckner tuderman", "bruckner tuderman 2009 .", "tuderman 2009 . during", "2009 . during fibrillogenesis", "during fibrillogenesis the", "fibrillogenesis the nascent", "the nascent type vii", "nascent type vii procollagen", "type vii procollagen molecules", "vii procollagen molecules dimerize", "procollagen molecules dimerize in", "molecules dimerize in an", "dimerize in an antiparallel", "in an antiparallel manner.", "an antiparallel manner. the", "antiparallel manner. the c", "manner. the c propeptides", "the c propeptides are", "c propeptides are then", "propeptides are then removed", "are then removed by", "then removed by bone", "removed by bone morphogenetic", "by bone morphogenetic protein", "bone morphogenetic protein 1", "protein 1 rattenholl", "1 rattenholl et", "rattenholl et al. 2002", "al. 2002 and", "2002 and the", "and the processed antiparallel", "the processed antiparallel dimers", "processed antiparallel dimers aggregate", "antiparallel dimers aggregate laterally.", "dimers aggregate laterally. collagens", "aggregate laterally. collagens viii", "laterally. collagens viii and", "collagens viii and x", "viii and x form", "and x form hexagonal", "x form hexagonal networks", "form hexagonal networks and", "hexagonal networks and collagen", "networks and collagen vi", "and collagen vi forms", "collagen vi forms beaded", "vi forms beaded filament", "beaded filament gordon", "filament gordon &", "ricard blum et al.", "blum et al. 2011", "collagen trimers in triple helical", "trimers in triple helical form", "triple helical form referred", "helical form referred to", "form referred to as", "referred to as procollagen or", "to as procollagen or collagen", "as procollagen or collagen molecules", "or collagen molecules are", "collagen molecules are exported", "molecules are exported from", "are exported from the er", "exported from the er and", "from the er and trafficked", "the er and trafficked through", "er and trafficked through the", "and trafficked through the golgi", "trafficked through the golgi network", "through the golgi network before", "the golgi network before secretion", "golgi network before secretion into", "network before secretion into the", "before secretion into the extracellular", "secretion into the extracellular space.", "into the extracellular space. for", "the extracellular space. for fibrillar", "extracellular space. for fibrillar collagens", "space. for fibrillar collagens namely", "for fibrillar collagens namely types", "fibrillar collagens namely types i", "namely types i ii", "i ii iii", "ii iii v", "iii v xi", "v xi xxiv", "xi xxiv and xxvii", "xxiv and xxvii gordon", "and xxvii gordon &", "xxvii gordon & hahn", "& hahn 2010 ricard", "hahn 2010 ricard blum", "2010 ricard blum 2011", "ricard blum 2011 secretion", "blum 2011 secretion is", "2011 secretion is concomitant", "secretion is concomitant with processing", "is concomitant with processing of", "concomitant with processing of the", "with processing of the n", "processing of the n and", "of the n and c", "the n and c terminal", "n and c terminal collagen", "and c terminal collagen propeptides.", "c terminal collagen propeptides. these", "terminal collagen propeptides. these processed", "collagen propeptides. these processed molecules", "propeptides. these processed molecules are", "these processed molecules are known", "processed molecules are known as", "molecules are known as tropocollagens", "known as tropocollagens considered", "as tropocollagens considered to", "tropocollagens considered to be", "considered to be the units", "to be the units of", "be the units of higher", "the units of higher order", "units of higher order collagen", "of higher order collagen structures.", "higher order collagen structures. they", "order collagen structures. they form", "collagen structures. they form within", "structures. they form within the", "they form within the extracellular", "form within the extracellular space", "within the extracellular space via", "the extracellular space via a", "extracellular space via a process", "space via a process that", "via a process that can", "a process that can proceed", "process that can proceed spontaneously", "can proceed spontaneously but", "proceed spontaneously but in", "spontaneously but in the", "but in the cellular environment", "in the cellular environment is", "the cellular environment is regulated", "cellular environment is regulated by", "environment is regulated by many", "is regulated by many collagen", "regulated by many collagen binding", "by many collagen binding proteins", "many collagen binding proteins such", "collagen binding proteins such as", "binding proteins such as the", "proteins such as the facit", "as the facit fibril", "the facit fibril associated", "facit fibril associated collagens", "fibril associated collagens with interrupted", "associated collagens with interrupted triple", "collagens with interrupted triple helices", "interrupted triple helices family", "triple helices family collagens", "helices family collagens and", "family collagens and small leucine", "collagens and small leucine rich", "and small leucine rich proteoglycans", "leucine rich proteoglycans slrps", "rich proteoglycans slrps .", "proteoglycans slrps . the", "slrps . the architecture formed", ". the architecture formed ultimately", "the architecture formed ultimately depends", "architecture formed ultimately depends on", "formed ultimately depends on the", "ultimately depends on the collagen", "depends on the collagen subtype", "on the collagen subtype and", "the collagen subtype and the", "collagen subtype and the cellular", "subtype and the cellular conditions.", "and the cellular conditions. structures", "the cellular conditions. structures include", "cellular conditions. structures include the", "conditions. structures include the well", "structures include the well known", "include the well known fibrils", "the well known fibrils and", "well known fibrils and fibres", "known fibrils and fibres formed", "fibrils and fibres formed by", "and fibres formed by the", "fibres formed by the major", "formed by the major structural", "by the major structural collagens", "the major structural collagens type", "major structural collagens type i", "structural collagens type i and", "collagens type i and ii", "type i and ii plus", "i and ii plus several", "and ii plus several different", "ii plus several different types", "plus several different types of", "several different types of supramolecular", "different types of supramolecular assembly", "of supramolecular assembly bruckner", "supramolecular assembly bruckner 2010", "assembly bruckner 2010 .", "bruckner 2010 . the mechanical", "2010 . the mechanical and", ". the mechanical and physical", "the mechanical and physical properties", "mechanical and physical properties of", "and physical properties of tissues", "physical properties of tissues depend", "properties of tissues depend on", "of tissues depend on the", "tissues depend on the spatial", "depend on the spatial arrangement", "on the spatial arrangement and", "the spatial arrangement and composition", "spatial arrangement and composition of", "arrangement and composition of these", "and composition of these collagen", "composition of these collagen containing", "of these collagen containing structures", "collagen containing structures kadler", "containing structures kadler et", "structures kadler et al.", "et al. 1996 shoulders", "al. 1996 shoulders &", "1996 shoulders & raines", "& raines 2009 birk", "raines 2009 birk &", "2009 birk & bruckner", "birk & bruckner 2011 .

", "& bruckner 2011 .

fibrillar", "bruckner 2011 .

fibrillar collagen", "2011 .

fibrillar collagen structures", ".

fibrillar collagen structures are", "fibrillar collagen structures are frequently", "collagen structures are frequently heterotypic", "are frequently heterotypic composed", "frequently heterotypic composed of", "heterotypic composed of a", "composed of a major collagen", "of a major collagen type", "a major collagen type in", "major collagen type in association", "collagen type in association with", "type in association with smaller", "in association with smaller amounts", "association with smaller amounts of", "with smaller amounts of other", "smaller amounts of other types", "of other types e.g.", "other types e.g. type", "types e.g. type i", "e.g. type i collagen fibrils", "type i collagen fibrils are", "i collagen fibrils are associated", "collagen fibrils are associated with", "fibrils are associated with types", "are associated with types iii", "associated with types iii and", "with types iii and v", "iii and v while", "and v while type", "v while type ii", "while type ii fibrils frequently", "type ii fibrils frequently contain", "ii fibrils frequently contain types", "fibrils frequently contain types ix", "frequently contain types ix and", "contain types ix and xi", "ix and xi wess", "and xi wess 2005", "xi wess 2005 .", "wess 2005 . fibres composed", "2005 . fibres composed exclusively", ". fibres composed exclusively of", "fibres composed exclusively of a", "composed exclusively of a single", "exclusively of a single collagen", "of a single collagen type", "a single collagen type probably", "single collagen type probably do", "collagen type probably do not", "type probably do not exist", "do not exist as", "not exist as type", "exist as type i", "as type i and ii", "type i and ii fibrils", "i and ii fibrils require", "and ii fibrils require collagens", "ii fibrils require collagens v", "fibrils require collagens v and", "require collagens v and xi", "collagens v and xi respectively", "v and xi respectively as", "and xi respectively as nucleators", "respectively as nucleators kadler", "as nucleators kadler et", "nucleators kadler et al.", "et al. 2008 wenstrup", "al. 2008 wenstrup et", "2008 wenstrup et al.", "wenstrup et al. 2011 .", "al. 2011 . much", "2011 . much of", ". much of the", "much of the structural understanding", "of the structural understanding of", "the structural understanding of collagen", "structural understanding of collagen fibrils", "understanding of collagen fibrils has", "of collagen fibrils has been", "collagen fibrils has been obtained", "fibrils has been obtained with", "has been obtained with fibril", "been obtained with fibril forming", "obtained with fibril forming collagens", "fibril forming collagens particularly", "forming collagens particularly type", "collagens particularly type i", "particularly type i but", "type i but some", "i but some central", "but some central features are", "some central features are believed", "central features are believed to", "features are believed to apply", "are believed to apply to", "believed to apply to at", "to apply to at least", "apply to at least the", "to at least the other", "at least the other fibrillar", "least the other fibrillar collagen", "the other fibrillar collagen subtypes", "fibrillar collagen subtypes wess", "collagen subtypes wess 2005", "subtypes wess 2005 .", "wess 2005 . fibril diameter", "2005 . fibril diameter and", ". fibril diameter and length", "fibril diameter and length varies", "diameter and length varies considerably", "length varies considerably depending", "varies considerably depending on", "considerably depending on the", "depending on the tissue and", "on the tissue and collagen", "the tissue and collagen types", "and collagen types fang", "collagen types fang et", "types fang et al.", "fang et al. 2012 .", "et al. 2012 . the", "al. 2012 . the reasons", "2012 . the reasons for", ". the reasons for this", "the reasons for this are", "reasons for this are poorly", "for this are poorly understood", "are poorly understood wess", "poorly understood wess 2005", "understood wess 2005 .

some", "wess 2005 .

some tissues such", "2005 .

some tissues such as", ".

some tissues such as skin", "tissues such as skin have", "such as skin have fibres", "as skin have fibres that", "skin have fibres that are", "have fibres that are approximately", "fibres that are approximately the", "that are approximately the same", "are approximately the same diameter", "approximately the same diameter while", "the same diameter while others", "same diameter while others such", "diameter while others such as", "while others such as tendon", "others such as tendon or", "such as tendon or cartilage", "as tendon or cartilage have", "tendon or cartilage have a", "or cartilage have a bimodal", "cartilage have a bimodal distribution", "have a bimodal distribution of", "a bimodal distribution of thick", "bimodal distribution of thick and", "distribution of thick and thin", "of thick and thin fibrils.", "thick and thin fibrils. mature", "and thin fibrils. mature type", "thin fibrils. mature type i", "fibrils. mature type i collagen", "mature type i collagen fibrils", "type i collagen fibrils in", "i collagen fibrils in tendon", "collagen fibrils in tendon are", "fibrils in tendon are up", "in tendon are up to", "tendon are up to 1", "are up to 1 cm", "up to 1 cm in", "to 1 cm in length", "cm in length with", "in length with a", "length with a diameter", "with a diameter of approx.", "a diameter of approx. 500", "diameter of approx. 500 nm.", "of approx. 500 nm. an", "approx. 500 nm. an individual", "500 nm. an individual fibrillar", "nm. an individual fibrillar collagen", "an individual fibrillar collagen triple", "individual fibrillar collagen triple helix", "fibrillar collagen triple helix is", "collagen triple helix is less", "triple helix is less than", "helix is less than 1.5", "is less than 1.5 nm", "less than 1.5 nm in", "than 1.5 nm in diameter", "1.5 nm in diameter and", "nm in diameter and around", "in diameter and around 300", "diameter and around 300 nm", "and around 300 nm long", "300 nm long collagen", "nm long collagen molecules", "long collagen molecules must", "collagen molecules must assemble to", "molecules must assemble to give", "must assemble to give rise", "assemble to give rise to", "to give rise to the", "give rise to the higher", "rise to the higher order", "to the higher order fibril", "the higher order fibril structure", "order fibril structure a", "fibril structure a process", "structure a process known", "a process known as fibrillogenesis", "known as fibrillogenesis prevented", "as fibrillogenesis prevented by", "fibrillogenesis prevented by the", "prevented by the presence of", "by the presence of c", "the presence of c terminal", "presence of c terminal propeptides", "c terminal propeptides kadler", "terminal propeptides kadler et", "propeptides kadler et al.", "kadler et al. 1987 .", "et al. 1987 . in", "al. 1987 . in electron", "1987 . in electron micrographs", "in electron micrographs fibrils", "electron micrographs fibrils have", "micrographs fibrils have a", "fibrils have a banded appearance", "a banded appearance due", "banded appearance due to", "appearance due to regular", "due to regular gaps where", "to regular gaps where fewer", "regular gaps where fewer collagen", "gaps where fewer collagen molecules", "where fewer collagen molecules overlap", "collagen molecules overlap which", "molecules overlap which occur", "overlap which occur because", "which occur because the fibrils", "occur because the fibrils are", "because the fibrils are aligned", "the fibrils are aligned in", "fibrils are aligned in a", "are aligned in a quarter", "aligned in a quarter stagger", "in a quarter stagger arrangement", "quarter stagger arrangement hodge", "stagger arrangement hodge &", "arrangement hodge & petruska", "hodge & petruska 1963 .", "& petruska 1963 . collagen", "petruska 1963 . collagen microfibrils", "1963 . collagen microfibrils are", ". collagen microfibrils are believed", "collagen microfibrils are believed to", "microfibrils are believed to have", "are believed to have a", "believed to have a quasi", "to have a quasi hexagonal", "have a quasi hexagonal unit", "a quasi hexagonal unit cell", "hexagonal unit cell with", "unit cell with tropocollagen", "cell with tropocollagen arranged", "with tropocollagen arranged to form", "tropocollagen arranged to form supertwisted", "to form supertwisted right", "form supertwisted right handed", "supertwisted right handed microfibrils", "right handed microfibrils that interdigitate", "handed microfibrils that interdigitate with", "microfibrils that interdigitate with neighbouring", "that interdigitate with neighbouring microfibrils", "with neighbouring microfibrils leading", "neighbouring microfibrils leading to", "microfibrils leading to a", "leading to a spiral like", "to a spiral like structure", "a spiral like structure for", "spiral like structure for the", "like structure for the mature", "structure for the mature collagen", "for the mature collagen fibril", "mature collagen fibril orgel", "collagen fibril orgel et", "fibril orgel et al.", "et al. 2006 holmes", "al. 2006 holmes &", "2006 holmes & kadler", "holmes & kadler 2006 .

neighbouring", "& kadler 2006 .

neighbouring tropocollagen", "kadler 2006 .

neighbouring tropocollagen monomers", "2006 .

neighbouring tropocollagen monomers interact", ".

neighbouring tropocollagen monomers interact with", "tropocollagen monomers interact with each", "monomers interact with each other", "interact with each other and", "with each other and are", "each other and are cross", "other and are cross linked", "and are cross linked covalently", "are cross linked covalently by", "cross linked covalently by lysyl", "linked covalently by lysyl oxidase", "by lysyl oxidase orgel", "lysyl oxidase orgel et", "oxidase orgel et al.", "et al. 2000 maki", "al. 2000 maki 2006", "2000 maki 2006 .", "maki 2006 . mature collagen", "2006 . mature collagen fibrils", ". mature collagen fibrils are", "mature collagen fibrils are stabilized", "collagen fibrils are stabilized by", "fibrils are stabilized by lysyl", "are stabilized by lysyl oxidase", "stabilized by lysyl oxidase mediated", "by lysyl oxidase mediated cross", "lysyl oxidase mediated cross links.", "oxidase mediated cross links. hydroxylysyl", "mediated cross links. hydroxylysyl pyridinoline", "cross links. hydroxylysyl pyridinoline and", "links. hydroxylysyl pyridinoline and lysyl", "hydroxylysyl pyridinoline and lysyl pyridinoline", "pyridinoline and lysyl pyridinoline cross", "and lysyl pyridinoline cross links", "lysyl pyridinoline cross links form", "pyridinoline cross links form between", "links form between hydroxy", "between hydroxy lysine", "hydroxy lysine and hydroxylysine", "lysine and hydroxylysine residues in", "and hydroxylysine residues in bone", "hydroxylysine residues in bone and", "residues in bone and cartilage", "bone and cartilage eyre", "and cartilage eyre et", "cartilage eyre et al.", "eyre et al. 1984 .", "et al. 1984 . arginoline", "al. 1984 . arginoline cross", "1984 . arginoline cross links", ". arginoline cross links can", "arginoline cross links can form", "cross links can form in", "links can form in cartilage", "form in cartilage eyre", "in cartilage eyre et", "al. 2010 mature", "2010 mature bovine", "mature bovine articular cartilage contains", "bovine articular cartilage contains roughly", "articular cartilage contains roughly equimolar", "cartilage contains roughly equimolar amounts", "contains roughly equimolar amounts of", "roughly equimolar amounts of arginoline", "equimolar amounts of arginoline and", "amounts of arginoline and hydroxylysyl", "of arginoline and hydroxylysyl pyridinoline", "arginoline and hydroxylysyl pyridinoline based", "and hydroxylysyl pyridinoline based on", "hydroxylysyl pyridinoline based on peptide", "pyridinoline based on peptide yields.", "based on peptide yields. mature", "on peptide yields. mature collagen", "peptide yields. mature collagen fibrils", "yields. mature collagen fibrils in", "mature collagen fibrils in skin", "collagen fibrils in skin are", "fibrils in skin are stabilized", "in skin are stabilized by", "skin are stabilized by the", "are stabilized by the lysyl", "stabilized by the lysyl oxidase", "by the lysyl oxidase mediated", "the lysyl oxidase mediated cross", "lysyl oxidase mediated cross link", "oxidase mediated cross link histidinohydroxylysinonorleucine", "cross link histidinohydroxylysinonorleucine yamauch", "link histidinohydroxylysinonorleucine yamauch et", "histidinohydroxylysinonorleucine yamauch et al.", "yamauch et al. 1987 .", "et al. 1987 . due", "al. 1987 . due to", "1987 . due to the", ". due to the quarter", "due to the quarter staggered", "to the quarter staggered arrangement", "the quarter staggered arrangement of", "quarter staggered arrangement of collagen", "staggered arrangement of collagen molecules", "arrangement of collagen molecules in", "of collagen molecules in a", "collagen molecules in a fibril", "in a fibril telopeptides", "a fibril telopeptides most", "fibril telopeptides most often", "telopeptides most often interact with", "most often interact with the", "often interact with the triple", "interact with the triple helix", "with the triple helix of", "the triple helix of a", "triple helix of a neighbouring", "helix of a neighbouring collagen", "of a neighbouring collagen molecule", "a neighbouring collagen molecule in", "neighbouring collagen molecule in the", "collagen molecule in the fibril", "in the fibril except", "the fibril except for", "fibril except for collagen", "except for collagen molecules in", "for collagen molecules in register", "collagen molecules in register staggered", "molecules in register staggered by", "in register staggered by 4d", "register staggered by 4d from", "staggered by 4d from another", "by 4d from another collagen", "4d from another collagen molecule.", "from another collagen molecule. fibril", "another collagen molecule. fibril aggregation", "collagen molecule. fibril aggregation in", "molecule. fibril aggregation in vitro", "fibril aggregation in vitro can", "aggregation in vitro can be", "in vitro can be unipolar", "vitro can be unipolar or", "can be unipolar or bipolar", "unipolar or bipolar influenced", "or bipolar influenced by", "bipolar influenced by temperature", "influenced by temperature and levels", "by temperature and levels of", "temperature and levels of c", "and levels of c proteinase", "of c proteinase suggesting", "c proteinase suggesting a", "proteinase suggesting a role", "suggesting a role for the", "a role for the n", "for the n and", "and c propeptides in", "c propeptides in regulation", "propeptides in regulation of the", "in regulation of the aggregation", "regulation of the aggregation process", "the aggregation process kadler", "aggregation process kadler et", "process kadler et al.", "kadler et al. 1996 .", "et al. 1996 . in", "al. 1996 . in vivo", ". in vivo collagen", "in vivo collagen molecules", "vivo collagen molecules at", "collagen molecules at the fibril", "molecules at the fibril surface", "at the fibril surface may", "the fibril surface may retain", "fibril surface may retain their", "surface may retain their n", "may retain their n propeptides", "their n propeptides suggesting", "n propeptides suggesting that", "propeptides suggesting that this", "suggesting that this may limit", "that this may limit further", "this may limit further accretion", "limit further accretion or", "further accretion or alternatively", "accretion or alternatively represents", "or alternatively represents a transient", "alternatively represents a transient stage", "represents a transient stage in", "a transient stage in a", "transient stage in a model", "stage in a model whereby", "in a model whereby fibrils", "a model whereby fibrils grow", "model whereby fibrils grow in", "whereby fibrils grow in diameter", "fibrils grow in diameter through", "grow in diameter through a", "in diameter through a cycle", "diameter through a cycle of", "through a cycle of deposition", "cycle of deposition cleavage", "of deposition cleavage and", "deposition cleavage and further", "and further deposition chapman", "further deposition chapman 1989", "deposition chapman 1989 .

in", "1989 .

in vivo fibrils", ".

in vivo fibrils are", "vivo fibrils are often", "fibrils are often composed from", "are often composed from more", "often composed from more than", "composed from more than one", "from more than one type", "more than one type of", "than one type of collagen.", "one type of collagen. type", "type of collagen. type iii", "of collagen. type iii collagen", "collagen. type iii collagen is", "type iii collagen is found", "iii collagen is found associated", "collagen is found associated with", "is found associated with type", "found associated with type i", "associated with type i collagen", "with type i collagen in", "type i collagen in dermal", "i collagen in dermal fibrils", "in dermal fibrils with", "dermal fibrils with the", "fibrils with the collagen", "with the collagen iii on", "the collagen iii on the", "collagen iii on the periphery", "on the periphery suggesting", "the periphery suggesting a", "periphery suggesting a regulatory", "a regulatory role fleischmajer", "regulatory role fleischmajer et", "role fleischmajer et al.", "fleischmajer et al. 1990 .", "et al. 1990 . type", "al. 1990 . type v", "1990 . type v collagen", ". type v collagen associates", "type v collagen associates with", "v collagen associates with type", "collagen associates with type i", "associates with type i collagen", "with type i collagen fibrils", "i collagen fibrils where", "collagen fibrils where it", "fibrils where it may", "where it may limit fibril", "it may limit fibril diameter", "limit fibril diameter birk", "fibril diameter birk et", "diameter birk et al.", "et al. 1990 white", "al. 1990 white et", "1990 white et al.", "white et al. 1997 .", "et al. 1997 . type", "al. 1997 . type ix", "1997 . type ix associates", ". type ix associates with", "type ix associates with the", "ix associates with the surface", "associates with the surface of", "with the surface of narrow", "the surface of narrow diameter", "surface of narrow diameter collagen", "of narrow diameter collagen ii", "narrow diameter collagen ii fibrils", "diameter collagen ii fibrils in", "collagen ii fibrils in cartilage", "ii fibrils in cartilage and", "fibrils in cartilage and the", "in cartilage and the cornea", "and the cornea wu", "the cornea wu et", "cornea wu et al.", "et al. 1992 eyre", "al. 1992 eyre et", "1992 eyre et al.", "eyre et al. 2004 .", "et al. 2004 . highly", "al. 2004 . highly specific", "2004 . highly specific patterns", ". highly specific patterns of", "highly specific patterns of crosslinking", "specific patterns of crosslinking sites", "patterns of crosslinking sites suggest", "of crosslinking sites suggest that", "crosslinking sites suggest that collagen", "sites suggest that collagen ix", "suggest that collagen ix functions", "that collagen ix functions in", "collagen ix functions in interfibrillar", "ix functions in interfibrillar networking", "in interfibrillar networking wess", "interfibrillar networking wess 2005", "networking wess 2005 .", "wess 2005 . type xii", "2005 . type xii and", ". type xii and xiv", "type xii and xiv collagens", "xii and xiv collagens are", "and xiv collagens are localized", "xiv collagens are localized near", "collagens are localized near the", "are localized near the surface", "localized near the surface of", "near the surface of banded", "the surface of banded collagen", "surface of banded collagen i", "of banded collagen i fibrils", "collagen i fibrils nishiyama", "i fibrils nishiyama et", "fibrils nishiyama et al.", "nishiyama et al. 1994 .", "et al. 1994 . certain", "al. 1994 . certain fibril", "1994 . certain fibril associated", ". certain fibril associated collagens", "certain fibril associated collagens with", "interrupted triple helices facits", "helices facits associate", "facits associate with the", "associate with the surface of", "with the surface of collagen", "the surface of collagen fibrils", "of collagen fibrils where", "collagen fibrils where they", "fibrils where they may", "where they may serve to", "they may serve to limit", "may serve to limit fibril", "serve to limit fibril fusion", "to limit fibril fusion and", "limit fibril fusion and thereby", "fibril fusion and thereby regulate", "fusion and thereby regulate fibril", "and thereby regulate fibril diameter", "regulate fibril diameter gordon", "fibril diameter gordon &", "diameter gordon & hahn", "gordon & hahn 2010 .", "& hahn 2010 . collagen", "hahn 2010 . collagen xv", ". collagen xv a", "collagen xv a member", "xv a member of", "a member of the multiplexin", "member of the multiplexin family", "the multiplexin family is", "multiplexin family is almost", "family is almost exclusively", "is almost exclusively associated with", "almost exclusively associated with the", "exclusively associated with the fibrillar", "associated with the fibrillar collagen", "with the fibrillar collagen network", "fibrillar collagen network in", "collagen network in very", "network in very close", "in very close proximity to", "very close proximity to the", "close proximity to the basement", "proximity to the basement membrane.", "to the basement membrane. in", "the basement membrane. in human", "basement membrane. in human tissues", "membrane. in human tissues collagen", "in human tissues collagen xv", "human tissues collagen xv is", "tissues collagen xv is seen", "collagen xv is seen linking", "xv is seen linking banded", "is seen linking banded collagen", "seen linking banded collagen fibers", "linking banded collagen fibers subjacent", "banded collagen fibers subjacent to", "collagen fibers subjacent to the", "fibers subjacent to the basement", "subjacent to the basement membrane", "the basement membrane amenta", "basement membrane amenta et", "membrane amenta et al.", "amenta et al. 2005 .", "et al. 2005 . type", "al. 2005 . type xiv", "2005 . type xiv collagen", "type xiv collagen slrps", "xiv collagen slrps and", "collagen slrps and discoidin", "slrps and discoidin domain receptors", "and discoidin domain receptors also", "discoidin domain receptors also regulate", "domain receptors also regulate fibrillogenesis", "also regulate fibrillogenesis ansorge", "regulate fibrillogenesis ansorge et", "fibrillogenesis ansorge et al.", "et al. 2009 kalamajski", "al. 2009 kalamajski et", "2009 kalamajski et al.", "et al. 2010 flynn", "al. 2010 flynn et", "2010 flynn et al.", "flynn et al. 2010 .

collagen", "et al. 2010 .

collagen ix", "al. 2010 .

collagen ix is", "2010 .

collagen ix is cross", ".

collagen ix is cross linked", "ix is cross linked to", "is cross linked to the", "cross linked to the surface", "linked to the surface of", "to the surface of collagen", "the surface of collagen type", "surface of collagen type ii", "of collagen type ii fibrils", "type ii fibrils eyre", "ii fibrils eyre et", "fibrils eyre et al.", "eyre et al. 1987 .", "et al. 1987 . type", "al. 1987 . type xii", "1987 . type xii and", "and xiv collagens are found", "xiv collagens are found in", "collagens are found in association", "are found in association with", "found in association with type", "in association with type i", "with type i walchli", "type i walchli et", "i walchli et al.", "et al. 1994 and", "al. 1994 and type", "1994 and type ii", "and type ii watt", "type ii watt et", "ii watt et al.", "al. 1992 eyre 2002", "eyre 2002 fibrils in", "2002 fibrils in cartilage.", "fibrils in cartilage. they are", "in cartilage. they are thought", "cartilage. they are thought to", "they are thought to associate", "are thought to associate non", "thought to associate non covalently", "to associate non covalently via", "associate non covalently via their", "non covalently via their col1/nc1", "covalently via their col1/nc1 domains", "their col1/nc1 domains watt", "col1/nc1 domains watt et", "domains watt et al.", "1992 eyre 2002 .", "eyre 2002 .

some", "2002 .

some non", ".

some non fibrillar", "

some non fibrillar collagens form", "non fibrillar collagens form supramolecular", "fibrillar collagens form supramolecular assemblies", "collagens form supramolecular assemblies that", "form supramolecular assemblies that are", "supramolecular assemblies that are distinct", "assemblies that are distinct from", "that are distinct from typical", "are distinct from typical fibrils.", "distinct from typical fibrils. collagen", "from typical fibrils. collagen vii", "typical fibrils. collagen vii forms", "fibrils. collagen vii forms anchoring", "collagen vii forms anchoring fibrils", "forms anchoring fibrils composed", "anchoring fibrils composed of", "fibrils composed of antiparallel", "composed of antiparallel dimers that", "of antiparallel dimers that connect", "antiparallel dimers that connect the", "dimers that connect the dermis", "that connect the dermis to", "connect the dermis to the", "the dermis to the epidermis", "to the epidermis bruckner", "the epidermis bruckner tuderman", "epidermis bruckner tuderman 2009", "bruckner tuderman 2009 . during", "tuderman 2009 . during fibrillogenesis", ". during fibrillogenesis the", "during fibrillogenesis the nascent", "fibrillogenesis the nascent type", "the nascent type vii procollagen", "nascent type vii procollagen molecules", "type vii procollagen molecules dimerize", "vii procollagen molecules dimerize in", "procollagen molecules dimerize in an", "molecules dimerize in an antiparallel", "dimerize in an antiparallel manner.", "in an antiparallel manner. the", "an antiparallel manner. the c", "antiparallel manner. the c propeptides", "manner. the c propeptides are", "the c propeptides are then", "c propeptides are then removed", "propeptides are then removed by", "are then removed by bone", "then removed by bone morphogenetic", "removed by bone morphogenetic protein", "by bone morphogenetic protein 1", "morphogenetic protein 1 rattenholl", "protein 1 rattenholl et", "1 rattenholl et al.", "et al. 2002 and", "al. 2002 and the", "2002 and the processed", "and the processed antiparallel dimers", "the processed antiparallel dimers aggregate", "processed antiparallel dimers aggregate laterally.", "antiparallel dimers aggregate laterally. collagens", "dimers aggregate laterally. collagens viii", "aggregate laterally. collagens viii and", "laterally. collagens viii and x", "collagens viii and x form", "viii and x form hexagonal", "and x form hexagonal networks", "x form hexagonal networks and", "form hexagonal networks and collagen", "hexagonal networks and collagen vi", "networks and collagen vi forms", "and collagen vi forms beaded", "collagen vi forms beaded filament", "forms beaded filament gordon", "beaded filament gordon &", "filament gordon & hahn", "2010 ricard blum et", "ricard blum et al. 2011", "blum et al. 2011 ." ] }, { "record_id": "GLY_000594_1_184", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2022870", "r hsa", "hsa 2022870", "r hsa 2022870" ] }, { "record_id": "GLY_000594_1_184", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "chondroitin sulfate", "sulfate biosynthesis", "chondroitin sulfate biosynthesis", "glycosaminoglycan consists", "consists of", "of n", "n acetylgalactosamine", "residues alternating", "alternating in", "in glycosidic", "glycosidic linkages", "linkages with", "with glucuronic", "glucuronic acid", "glca .", ". galnac", "galnac residues", "residues are", "are sulfated", "sulfated to", "to varying", "varying degrees", "degrees on", "on 4", "and/or 6", "positions. the", "the steps", "steps below", "below describe", "describe the", "the biosynthesis", "biosynthesis of", "of a", "a simple", "simple cs", "cs molecule", "pavao et", "et al.", "al. 2006", "silbert &", "& sugumaran", "sugumaran 2002", "2002 .", "sulfate cs", "cs glycosaminoglycan", "glycosaminoglycan consists of", "consists of n", "of n acetylgalactosamine", "acetylgalactosamine galnac", 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sulfated", "sulfated glucosamine", "stringer &", "& gallagher", "gallagher 1997", "sasisekharan &", "& venkataraman", "venkataraman 2000", "2000 .", "sulfate hs", "hs and", "heparin sometimes", "sometimes collectively called", "collectively called hs", "called hs gag", "gag consist", "consist of the", "of the disaccharide", "the disaccharide unit", "disaccharide unit glcnac", "unit glcnac glca", "glca n", "n acetylglucosamine glucuronic", "acetylglucosamine glucuronic acid", "acid connected", "connected by a", "by a beta1", "a beta1 4", "beta1 4 linkage.", "4 linkage. heparin", "linkage. heparin is", "heparin is exclusively", "is exclusively made", "exclusively made in", "made in mast", "in mast cells", "mast cells whereas", "cells whereas hs", "whereas hs is", "hs is made", "is made by", "made by virtually", "by virtually every", "virtually every type", "every type of", "type of cell", "of cell in", "cell in the", "in the body.", "the body. as", "body. as the", "as the chain", "the chain length", "chain length increases", "increases the", "the polysaccharides can", "polysaccharides can undergo", "can undergo modifcations", "undergo modifcations such", "modifcations such as", "such as epimerisation", "as epimerisation of", "epimerisation of glucuronic", "of glucuronic acid", "glucuronic acid to", "acid to iduronic", "to iduronic acid", "iduronic acid and", "acid and deacetylation", "and deacetylation and", "deacetylation and sulfation", "and sulfation of", "sulfation of glcnac", "of glcnac to", "glcnac to form", "to form sulfated", "form sulfated glucosamine", "glucosamine stringer", "stringer & gallagher", "& gallagher 1997", "1997 sasisekharan", "sasisekharan & venkataraman", "& venkataraman 2000", "venkataraman 2000 .", "heparan sulfate hs", "hs and heparin", "and heparin sometimes", "heparin sometimes collectively", "sometimes collectively called hs", "collectively called hs gag", "hs gag consist", "gag consist of", "consist of the disaccharide", "of the disaccharide unit", "the disaccharide unit glcnac", "disaccharide unit glcnac glca", "glcnac glca n", "glca n acetylglucosamine", "n acetylglucosamine glucuronic acid", "glucuronic acid connected", "acid connected by", "connected by a beta1", "by a beta1 4", "a beta1 4 linkage.", "beta1 4 linkage. heparin", "4 linkage. heparin is", "linkage. heparin is exclusively", "heparin is exclusively made", "is exclusively made in", "exclusively made in mast", "made in mast cells", "in mast cells whereas", "mast cells whereas hs", "cells whereas hs is", "whereas hs is made", "hs is made by", "is made by virtually", "made by virtually every", "by virtually every type", "virtually every type of", "every type of cell", "type of cell in", "of cell in the", "cell in the body.", "in the body. as", "the body. as the", "body. as the chain", "as the chain length", "the chain length increases", "length increases the", "increases the polysaccharides", "the polysaccharides can undergo", "polysaccharides can undergo modifcations", "can undergo modifcations such", "undergo modifcations such as", "modifcations such as epimerisation", "such as epimerisation of", "as epimerisation of glucuronic", "epimerisation of glucuronic acid", "of glucuronic acid to", "glucuronic acid to iduronic", "acid to iduronic acid", "to iduronic acid and", "iduronic acid and deacetylation", "acid and deacetylation and", "and deacetylation and sulfation", "deacetylation and sulfation of", "and sulfation of glcnac", "sulfation of glcnac to", "of glcnac to form", "glcnac to form sulfated", "to form sulfated glucosamine", "sulfated glucosamine stringer", "glucosamine stringer &", "stringer & gallagher 1997", "gallagher 1997 sasisekharan", "1997 sasisekharan &", "sasisekharan & venkataraman 2000", "& venkataraman 2000 .", "sulfate hs and", "and heparin sometimes collectively", "heparin sometimes collectively called", "sometimes collectively called hs gag", "called hs gag consist", "hs gag consist of", "gag consist of 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as the", "the body. as the chain", "body. as the chain length", "as the chain length increases", "chain length increases the", "length increases the polysaccharides", "increases the polysaccharides can", "the polysaccharides can undergo modifcations", "polysaccharides can undergo modifcations such", "can undergo modifcations such as", "undergo modifcations such as epimerisation", "modifcations such as epimerisation of", "such as epimerisation of glucuronic", "as epimerisation of glucuronic acid", "epimerisation of glucuronic acid to", "of glucuronic acid to iduronic", "glucuronic acid to iduronic acid", "acid to iduronic acid and", "to iduronic acid and deacetylation", "iduronic acid and deacetylation and", "acid and deacetylation and sulfation", "and deacetylation and sulfation of", "deacetylation and sulfation of glcnac", "and sulfation of glcnac to", "sulfation of glcnac to form", "of glcnac to form sulfated", "glcnac to form sulfated glucosamine", "form sulfated glucosamine 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stimulated", "stimulated changes", "namely nfkappab", "nfat and", "and ap", "ap 1.", "1. a", "key step", "step in", "in nfkappab", "nfkappab activation", "activation is", "is the", "the stimulation", "stimulation and", "and translocation", "translocation of", "of prkcq.", "prkcq. the", "the critical", "critical element", "element that", "that effects", "effects prkcq", "prkcq activation", "is pi3k.", "pi3k. pi3k", "pi3k translocates", "translocates to", "to the", "the plasma", "plasma membrane", "membrane by", "by interacting", "interacting with", "with phospho", "phospho tyrosines", "tyrosines on", "on cd28", "cd28 via", "via its", "its two", "two sh2", "sh2 domains", "domains located", "located in", "in p85", "p85 subunit", "step 24", "24 .", ". the", "the p110", "p110 subunit", "subunit of", "of pi3k", "pi3k phosphorylates", "phosphorylates the", "the inositol", "inositol ring", "ring of", "of pip2", "pip2 to", "to generate", "generate pip3", "steps 25", "25 .", "the reverse", "reverse dephosphorylation", "dephosphorylation process", "process from", "from pip3", "pip3 to", "to pip2", "pip2 is", "is catalysed", "catalysed by", "by pten", "step 27", "27 .", ". pip3", "pip3 may", "may also", "also be", "be dephosphorylated", "dephosphorylated by", "by the", "the phosphatase", "phosphatase ship", "ship to", "generate pi", "pi 3", "3 4", "4 p2", "step 26", "26 .", "pip3 and", "and pi", "p2 acts", "acts as", "as binding", "binding sites", "sites to", "the ph", "ph domain", "domain of", "of pdk1", "step 28", "and akt", "step 29", "29 .", ". pkb", "pkb is", "is activated", "activated in", "in response", "response to", "to pi3k", "pi3k stimulation", "stimulation by", "by pdk1", "step 30", "30 .", ". pdk1", "pdk1 has", "has an", "an essential", "essential role", "in regulating", "regulating the", "the activation", "activation of", "of prkcq", "prkcq and", "and recruitment", "recruitment of", "of cbm", "cbm complex", "complex to", "the immune", "immune synapse.", 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"on threonine", "threonine 538", "step 33", "33 .", ". this", "this step", "step is", "is critical", "critical for", "for pkc", "pkc activity.", "activity. carma1", "carma1 translocates", "membrane following", "following the", "the interaction", "interaction of", "of its", "its sh3", "sh3 domain", "domain with", "with the", "the 'pxxp'", "'pxxp' motif", "motif on", "on pdk1", "step 34", "34 .", ". carma1", "carma1 is", "is phosphorylated", "by pkc", "pkc theta", "theta on", "on residue", "residue s552", "step 35", "leading to", "the oligomerization", "oligomerization of", "of carma1.", "carma1. this", "this complex", "complex acts", "as a", "a scaffold", "recruiting bcl10", "bcl10 to", "the synapse", "synapse by", "with their", "their card", "card domains", "step 36", "36 .", ". bcl10", "bcl10 undergoes", "phosphorylation mediated", "mediated by", "the enzyme", "enzyme rip2", "step 37", "37 .", ". activated", "activated bcl10", "bcl10 then", "then mediates", "mediates the", "the ubiquitination", "ubiquitination of", "of ikbkg", "ikbkg by", "by recruiting", "recruiting malt1", "malt1 and", "and traf6.", "traf6. malt1", "malt1 binds", "to bcl10", "bcl10 with", "with its", "its ig", "ig like", "like domains", "domains and", "undergoes oligomerization", "step 38", "38 .", ". traf6", "traf6 binds", "the oligomerized", "oligomerized malt1", "and also", "also undergoes", "step 39", "39 .", ". oligomerized", "oligomerized traf6", "traf6 acts", "a ubiquitin", "ubiquitin protein", "protein ligase", "catalyzing auto", "auto k63", "k63 linked", "linked polyubiquitination", "step 40", "40 .", "this k", "k 63", "63 ubiquitinated", "ubiquitinated traf6", "traf6 activates", "activates map3k7", "map3k7 kinase", "kinase bound", "bound to", "to tab2", "step 41", "also ubiquitinates", "ubiquitinates ikbkg", "ikbkg in", "in the", "the ikk", "ikk complex", "step 44", "44 .", ". map3k7", "map3k7 undergoes", "undergoes autophosphorylation", "autophosphorylation on", "on residues", "residues t184", "t184 and", "and t187", "t187 and", "and gets", "gets activated", "step 42", "42 .", "activated map3k7", "kinase phosphorylates", "phosphorylates ikbkb", "ikbkb on", "residues s177", "s177 and", "and s181", "s181 in", "activation loop", "loop and", "and activates", "activates the", "ikk kinase", "kinase activity", "step 43", "43 .", ". ikbkb", "ikbkb phosphorylates", "the nfkbia", "nfkbia bound", "the nfkappab", "nfkappab heterodimer", "residues s19", "s19 and", "and s23", "step 45", "and directs", "directs nfkbia", "nfkbia to", "to 26s", "26s proteasome", "proteasome degradation", "step 47", "47 .", "heterodimer with", "with a", "a free", "free nts", "nts sequence", "sequence finally", "finally migrates", "migrates to", "the nucleus", "nucleus to", "to regulate", "regulate gene", "gene transcription", "step 46", "46 .", "changes in gene", "in gene expression", "gene expression are", "expression are required", "are required for", "required for the", "for the t", "the t cell", "t cell to", "cell to gain", "to gain full", "gain full proliferative", "full proliferative competence", "proliferative competence and", "competence and to", "and to produce", "to produce effector", "produce effector cytokines.", "effector cytokines. three", "cytokines. three transcription", "three transcription factors", "transcription factors in", "factors in particular", "in particular have", "particular have been", "have been found", "been found to", "found to play", "to play a", "play a key", "a key role", "key role in", "role in tcr", "in tcr stimulated", "tcr stimulated changes", "stimulated changes in", "expression namely", "nfkappab nfat", "nfat and ap", "and ap 1.", "ap 1. a", "1. a key", "a key step", "key step in", "step in nfkappab", "in nfkappab activation", "nfkappab activation is", "activation is the", "is the stimulation", "the stimulation and", "stimulation and translocation", "and translocation of", "translocation of prkcq.", "of prkcq. the", "prkcq. the critical", "the critical element", "critical element that", "element that effects", "that effects prkcq", "effects prkcq activation", "prkcq activation is", "activation is pi3k.", "is pi3k. pi3k", "pi3k. pi3k translocates", "pi3k translocates to", "translocates to the", "to the plasma", "the plasma membrane", "plasma membrane by", "membrane by interacting", "by interacting with", "interacting with phospho", "with phospho tyrosines", "phospho tyrosines on", "tyrosines on cd28", "on cd28 via", "cd28 via its", "via its two", "its two sh2", "two sh2 domains", "sh2 domains located", "domains located in", "located in p85", "in p85 subunit", "subunit step", "step 24 .", "24 . the", ". the p110", "the p110 subunit", "p110 subunit of", "subunit of pi3k", "of pi3k phosphorylates", "pi3k phosphorylates the", "phosphorylates the inositol", "the inositol ring", "inositol ring of", "ring of pip2", "of pip2 to", "pip2 to generate", "to generate pip3", "pip3 steps", "steps 25 .", "25 . the", ". the reverse", "the reverse dephosphorylation", "reverse dephosphorylation process", "dephosphorylation process from", "process from pip3", "from pip3 to", "pip3 to pip2", "to pip2 is", "pip2 is catalysed", "is catalysed by", "catalysed by pten", "pten step", "step 27 .", "27 . pip3", ". pip3 may", "pip3 may also", "may also be", "also be dephosphorylated", "be dephosphorylated by", "dephosphorylated by the", "by the phosphatase", "the phosphatase ship", "phosphatase ship to", "ship to generate", "to generate pi", "generate pi 3", "pi 3 4", "3 4 p2", "p2 step", "step 26 .", "26 . pip3", ". pip3 and", "pip3 and pi", "and pi 3", "4 p2 acts", "p2 acts as", "acts as binding", "as binding sites", "binding sites to", "sites to the", "to the ph", "the ph domain", "ph domain of", "domain of pdk1", "pdk1 step", "28 and", "akt step", "step 29 .", "29 . pkb", ". pkb is", "pkb is activated", "is activated in", "activated in response", "in response to", "response to pi3k", "to pi3k stimulation", "pi3k stimulation by", "stimulation by pdk1", "step 30 .", "30 . pdk1", ". pdk1 has", "pdk1 has an", "has an essential", "an essential role", "essential role in", "role in regulating", "in regulating the", "regulating the activation", "the activation of", "activation of prkcq", "of prkcq and", "prkcq and recruitment", "and recruitment of", "recruitment of cbm", "of cbm complex", "cbm complex to", "complex to the", "to the immune", "the immune synapse.", "immune synapse. prkcq", "synapse. prkcq is", "prkcq is a", "is a member", "a member of", "member of novel", "of novel class", "class dag", "dependent ca++", "independent of", "of pkc and", "pkc and the", "and the only", "the only member", "only member known", "member known to", "known to translocate", "to translocate to", "translocate to this", "to this synapse.", "this synapse. prior", "synapse. prior to", "prior to tcr", "to tcr stimulation", "tcr stimulation prkcq", "stimulation prkcq exists", "prkcq exists in", "exists in an", "in an inactive", "an inactive closed", "inactive closed conformation.", "closed conformation. tcr", "conformation. tcr signals", "tcr signals stimulate", "signals stimulate prkcq", "prkcq step", "31 and", "and release dag", "release dag molecules.", "dag molecules. subsequently", "subsequently dag", "dag binds to", "binds to prkcq", "to prkcq via", "prkcq via the", "via the c1", "the c1 domain", "c1 domain and", "domain and undergoes", "and undergoes phosphorylation", "undergoes phosphorylation on", "phosphorylation on tyrosine", "on tyrosine 90", "tyrosine 90 by", "90 by lck", "by lck to", "lck to attain", "to attain an", "attain an open", "an open conformation", "conformation step", "step 32 .", "32 . prkcq", ". prkcq is", "prkcq is further", "is further phosphorylated", "further phosphorylated by", "phosphorylated by pdk1", "by pdk1 on", "pdk1 on threonine", "on threonine 538", "538 step", "step 33 .", "33 . this", ". this step", "this step is", "step is critical", "is critical for", "critical for pkc", "for pkc activity.", "pkc activity. carma1", "activity. carma1 translocates", "carma1 translocates to", "plasma membrane following", "membrane following the", "following the interaction", "the interaction of", "interaction of its", "of its sh3", "its sh3 domain", "sh3 domain with", "domain with the", "with the 'pxxp'", "the 'pxxp' motif", "'pxxp' motif on", "motif on pdk1", "step 34 .", "34 . carma1", ". carma1 is", "carma1 is phosphorylated", "is phosphorylated by", "phosphorylated by pkc", "by pkc theta", "pkc theta on", "theta on residue", "on residue s552", "s552 step", "leading to the", "to the oligomerization", "the oligomerization of", "oligomerization of carma1.", "of carma1. this", "carma1. this complex", "this complex acts", "complex acts as", "acts as a", "as a scaffold", "scaffold recruiting", "recruiting bcl10 to", "bcl10 to the", "to the synapse", "the synapse by", "synapse by interacting", "interacting with their", "with their card", "their card domains", "domains step", "step 36 .", "36 . bcl10", ". bcl10 undergoes", "bcl10 undergoes phosphorylation", "undergoes phosphorylation mediated", "phosphorylation mediated by", "mediated by the", "by the enzyme", "the enzyme rip2", "rip2 step", "step 37 .", "37 . activated", ". activated bcl10", "activated bcl10 then", "bcl10 then mediates", "then mediates the", "mediates the ubiquitination", "the ubiquitination of", "ubiquitination of ikbkg", "of ikbkg by", "ikbkg by recruiting", "by recruiting malt1", "recruiting malt1 and", "malt1 and traf6.", "and traf6. malt1", "traf6. malt1 binds", "malt1 binds to", "binds to bcl10", "to bcl10 with", "bcl10 with its", "with its ig", "its ig like", "ig like domains", "like domains and", "domains and undergoes", "and undergoes oligomerization", "oligomerization step", "step 38 .", "38 . traf6", ". traf6 binds", "traf6 binds to", "binds to the", "to the oligomerized", "the oligomerized malt1", "oligomerized malt1 and", "malt1 and also", "and also undergoes", "also undergoes oligomerization", "step 39 .", "39 . oligomerized", ". oligomerized traf6", "oligomerized traf6 acts", "traf6 acts as", "as a ubiquitin", "a ubiquitin protein", "ubiquitin protein ligase", "ligase catalyzing", "catalyzing auto k63", "auto k63 linked", "k63 linked polyubiquitination", "polyubiquitination step", "step 40 .", "40 . this", ". this k", "this k 63", "k 63 ubiquitinated", "63 ubiquitinated traf6", "ubiquitinated traf6 activates", "traf6 activates map3k7", "activates map3k7 kinase", "map3k7 kinase bound", "kinase bound to", "bound to tab2", "tab2 step", "41 and", "and also ubiquitinates", "also ubiquitinates ikbkg", "ubiquitinates ikbkg in", "ikbkg in the", "in the ikk", "the ikk complex", "complex step", "step 44 .", "44 . map3k7", ". map3k7 undergoes", "map3k7 undergoes autophosphorylation", "undergoes autophosphorylation on", "autophosphorylation on residues", "on residues t184", "residues t184 and", "t184 and t187", "and t187 and", "t187 and gets", "and gets activated", "activated step", "step 42 .", "42 . activated", ". activated map3k7", "activated map3k7 kinase", "map3k7 kinase phosphorylates", "kinase phosphorylates ikbkb", "phosphorylates ikbkb on", "ikbkb on residues", "on residues s177", "residues s177 and", "s177 and s181", "and s181 in", "s181 in the", "in the activation", "the activation loop", "activation loop and", "loop and activates", "and activates the", "activates the ikk", "the ikk kinase", "ikk kinase activity", "activity step", "step 43 .", "43 . ikbkb", ". ikbkb phosphorylates", "ikbkb phosphorylates the", "phosphorylates the nfkbia", "the nfkbia bound", "nfkbia bound to", "bound to the", "to the nfkappab", "the nfkappab heterodimer", "heterodimer on", "on residues s19", "residues s19 and", "s19 and s23", "s23 step", "45 and", "and directs nfkbia", "directs nfkbia to", "nfkbia to 26s", "to 26s proteasome", "26s proteasome degradation", "degradation step", "step 47 .", "47 . the", ". the nfkappab", "nfkappab heterodimer with", "heterodimer with a", "with a free", "a free nts", "free nts sequence", "nts sequence finally", "sequence finally migrates", "finally migrates to", "migrates to the", "to the nucleus", "the nucleus to", "nucleus to regulate", "to regulate gene", "regulate gene transcription", "transcription step", "step 46 .", "changes in gene expression", "in gene expression are", "gene expression are required", "expression are required for", "are required for the", "required for the t", "for the t cell", "the t cell to", "t cell to gain", "cell to gain full", "to gain full proliferative", "gain full proliferative competence", "full proliferative competence and", "proliferative competence and to", "competence and to produce", "and to produce effector", "to produce effector cytokines.", "produce effector cytokines. three", "effector cytokines. three transcription", "cytokines. three transcription factors", "three transcription factors in", "transcription factors in particular", "factors in particular have", "in particular have been", "particular have been found", "have been found to", "been found to play", "found to play a", "to play a key", "play a key role", "a key role in", "key role in tcr", "role in tcr stimulated", "in tcr stimulated changes", "tcr stimulated changes in", "stimulated changes in gene", "gene expression namely", "expression namely nfkappab", "namely nfkappab nfat", "nfkappab nfat and", "nfat and ap 1.", "and ap 1. a", "ap 1. a key", "1. a key step", "a key step in", "key step in nfkappab", "step in nfkappab activation", "in nfkappab activation is", "nfkappab activation is the", "activation is the stimulation", "is the stimulation and", "the stimulation and translocation", "stimulation and translocation of", "and translocation of prkcq.", "translocation of prkcq. the", "of prkcq. the critical", "prkcq. the critical element", "the critical element that", "critical element that effects", "element that effects prkcq", "that effects prkcq activation", "effects prkcq activation is", "prkcq activation is pi3k.", "activation is pi3k. pi3k", "is pi3k. pi3k translocates", "pi3k. pi3k translocates to", "pi3k translocates to the", "translocates to the plasma", "to the plasma membrane", "the plasma membrane by", "plasma membrane by interacting", "membrane by interacting with", "by interacting with phospho", "interacting with phospho tyrosines", "with phospho tyrosines on", "phospho tyrosines on cd28", "tyrosines on cd28 via", "on cd28 via its", "cd28 via its two", "via its two sh2", "its two sh2 domains", "two sh2 domains located", "sh2 domains located in", "domains located in p85", "located in p85 subunit", "p85 subunit step", "subunit step 24", "step 24 . the", "24 . the p110", ". the p110 subunit", "the p110 subunit of", "p110 subunit of pi3k", "subunit of pi3k phosphorylates", "of pi3k phosphorylates the", "pi3k phosphorylates the inositol", "phosphorylates the inositol ring", "the inositol ring of", "inositol ring of pip2", "ring of pip2 to", "of pip2 to generate", "pip2 to generate pip3", "generate pip3 steps", "pip3 steps 25", "steps 25 . the", "25 . the reverse", ". the reverse dephosphorylation", "the reverse dephosphorylation process", "reverse dephosphorylation process from", "dephosphorylation process from pip3", "process from pip3 to", "from pip3 to pip2", "pip3 to pip2 is", "to pip2 is catalysed", "pip2 is catalysed by", "is catalysed by pten", "by pten step", "pten step 27", "step 27 . pip3", "27 . pip3 may", ". pip3 may also", "pip3 may also be", "may also be dephosphorylated", "also be dephosphorylated by", "be dephosphorylated by the", "dephosphorylated by the phosphatase", "by the phosphatase ship", "the phosphatase ship to", "phosphatase ship to generate", "ship to generate pi", "to generate pi 3", "generate pi 3 4", "pi 3 4 p2", "4 p2 step", "p2 step 26", "step 26 . pip3", "26 . pip3 and", ". pip3 and pi", "pip3 and pi 3", "and pi 3 4", "3 4 p2 acts", "4 p2 acts as", "p2 acts as binding", "acts as binding sites", "as binding sites to", "binding sites to the", "sites to the ph", "to the ph domain", "the ph domain of", "ph domain of pdk1", "of pdk1 step", "pdk1 step 28", "step 28 and", "28 and akt", "and akt step", "akt step 29", "step 29 . pkb", "29 . pkb is", ". pkb is activated", "pkb is activated in", "is activated in response", "activated in response to", "in response to pi3k", "response to pi3k stimulation", "to pi3k stimulation by", "pi3k stimulation by pdk1", "by pdk1 step", "pdk1 step 30", "step 30 . pdk1", "30 . pdk1 has", ". pdk1 has an", "pdk1 has an essential", "has an essential role", "an essential role in", "essential role in regulating", "role in regulating the", "in regulating the activation", "regulating the activation of", "the activation of prkcq", "activation of prkcq and", "of prkcq and recruitment", "prkcq and recruitment of", "and recruitment of cbm", "recruitment of cbm complex", "of cbm complex to", "cbm complex to the", "complex to the immune", "to the immune synapse.", "the immune synapse. prkcq", "immune synapse. prkcq is", "synapse. prkcq is a", "prkcq is a member", "is a member of", "a member of novel", "member of novel class", "novel class dag", "class dag dependent", "dag dependent ca++", "dependent ca++ independent", "ca++ independent of", "independent of pkc", "of pkc and the", "pkc and the only", "and the only member", "the only member known", "only member known to", "member known to translocate", "known to translocate to", "to translocate to this", "translocate to this synapse.", "to this synapse. prior", "this synapse. prior to", "synapse. prior to tcr", "prior to tcr stimulation", "to tcr stimulation prkcq", "tcr stimulation prkcq exists", "stimulation prkcq exists in", "prkcq exists in an", "exists in an inactive", "in an inactive closed", "an inactive closed conformation.", "inactive closed conformation. tcr", "closed conformation. tcr signals", "conformation. tcr signals stimulate", "tcr signals stimulate prkcq", "stimulate prkcq step", "prkcq step 31", "step 31 and", "31 and release", "and release dag molecules.", "release dag molecules. subsequently", "molecules. subsequently dag", "subsequently dag binds", "dag binds to prkcq", "binds to prkcq via", "to prkcq via the", "prkcq via the c1", "via the c1 domain", "the c1 domain and", "c1 domain and undergoes", "domain and undergoes phosphorylation", "and undergoes phosphorylation on", "undergoes phosphorylation on tyrosine", "phosphorylation on tyrosine 90", "on tyrosine 90 by", "tyrosine 90 by lck", "90 by lck to", "by lck to attain", "lck to attain an", "to attain an open", "attain an open conformation", "open conformation step", "conformation step 32", "step 32 . prkcq", "32 . prkcq is", ". prkcq is further", "prkcq is further phosphorylated", "is further phosphorylated by", "further phosphorylated by pdk1", "phosphorylated by pdk1 on", "by pdk1 on threonine", "pdk1 on threonine 538", "threonine 538 step", "538 step 33", "step 33 . this", "33 . this step", ". this step is", "this step is critical", "step is critical for", "is critical for pkc", "critical for pkc activity.", "for pkc activity. carma1", "pkc activity. carma1 translocates", "activity. carma1 translocates to", "carma1 translocates to the", "the plasma membrane following", "plasma membrane following the", "membrane following the interaction", "following the interaction of", "the interaction of its", "interaction of its sh3", "of its sh3 domain", "its sh3 domain with", "sh3 domain with the", "domain with the 'pxxp'", "with the 'pxxp' motif", "the 'pxxp' motif on", "'pxxp' motif on pdk1", "on pdk1 step", "pdk1 step 34", "step 34 . carma1", "34 . carma1 is", ". carma1 is phosphorylated", "carma1 is phosphorylated by", "is phosphorylated by pkc", "phosphorylated by pkc theta", "by pkc theta on", "pkc theta on residue", "theta on residue s552", "residue s552 step", "s552 step 35", "35 leading", "leading to the oligomerization", "to the oligomerization of", "the oligomerization of carma1.", "oligomerization of carma1. this", "of carma1. this complex", "carma1. this complex acts", "this complex acts as", "complex acts as a", "acts as a scaffold", "a scaffold recruiting", "scaffold recruiting bcl10", "recruiting bcl10 to the", "bcl10 to the synapse", "to the synapse by", "the synapse by interacting", "synapse by interacting with", "by interacting with their", "interacting with their card", "with their card domains", "card domains step", "domains step 36", "step 36 . bcl10", "36 . bcl10 undergoes", ". bcl10 undergoes phosphorylation", "bcl10 undergoes phosphorylation mediated", "undergoes phosphorylation mediated by", "phosphorylation mediated by the", "mediated by the enzyme", "by the enzyme rip2", "enzyme rip2 step", "rip2 step 37", "step 37 . activated", "37 . activated bcl10", ". activated bcl10 then", "activated bcl10 then mediates", "bcl10 then mediates the", "then mediates the ubiquitination", "mediates the ubiquitination of", "the ubiquitination of ikbkg", "ubiquitination of ikbkg by", "of ikbkg by recruiting", "ikbkg by recruiting malt1", "by recruiting malt1 and", "recruiting malt1 and traf6.", "malt1 and traf6. malt1", "and traf6. malt1 binds", "traf6. malt1 binds to", "malt1 binds to bcl10", "binds to bcl10 with", "to bcl10 with its", "bcl10 with its ig", "with its ig like", "its ig like domains", "ig like domains and", "like domains and undergoes", "domains and undergoes oligomerization", "undergoes oligomerization step", "oligomerization step 38", "step 38 . traf6", "38 . traf6 binds", ". traf6 binds to", "traf6 binds to the", "binds to the oligomerized", "to the oligomerized malt1", "the oligomerized malt1 and", "oligomerized malt1 and also", "malt1 and also undergoes", "and also undergoes oligomerization", "oligomerization step 39", "step 39 . oligomerized", "39 . oligomerized traf6", ". oligomerized traf6 acts", "oligomerized traf6 acts as", "traf6 acts as a", "acts as a ubiquitin", "as a ubiquitin protein", "a ubiquitin protein ligase", "protein ligase catalyzing", "ligase catalyzing auto", "catalyzing auto k63 linked", "auto k63 linked polyubiquitination", "linked polyubiquitination step", "polyubiquitination step 40", "step 40 . this", "40 . this k", ". this k 63", "this k 63 ubiquitinated", "k 63 ubiquitinated traf6", "63 ubiquitinated traf6 activates", "ubiquitinated traf6 activates map3k7", "traf6 activates map3k7 kinase", "activates map3k7 kinase bound", "map3k7 kinase bound to", "kinase bound to tab2", "to tab2 step", "tab2 step 41", "step 41 and", "41 and also", "and also ubiquitinates ikbkg", "also ubiquitinates ikbkg in", "ubiquitinates ikbkg in the", "ikbkg in the ikk", "in the ikk complex", "ikk complex step", "complex step 44", "step 44 . map3k7", "44 . map3k7 undergoes", ". map3k7 undergoes autophosphorylation", "map3k7 undergoes autophosphorylation on", "undergoes autophosphorylation on residues", "autophosphorylation on residues t184", "on residues t184 and", "residues t184 and t187", "t184 and t187 and", "and t187 and gets", "t187 and gets activated", "gets activated step", "activated step 42", "step 42 . activated", "42 . activated map3k7", ". activated map3k7 kinase", "activated map3k7 kinase phosphorylates", "map3k7 kinase phosphorylates ikbkb", "kinase phosphorylates ikbkb on", "phosphorylates ikbkb on residues", "ikbkb on residues s177", "on residues s177 and", "residues s177 and s181", "s177 and s181 in", "and s181 in the", "s181 in the activation", "in the activation loop", "the activation loop and", "activation loop and activates", "loop and activates the", "and activates the ikk", "activates the ikk kinase", "the ikk kinase activity", "kinase activity step", "activity step 43", "step 43 . ikbkb", "43 . ikbkb phosphorylates", ". ikbkb phosphorylates the", "ikbkb phosphorylates the nfkbia", "phosphorylates the nfkbia bound", "the nfkbia bound to", "nfkbia bound to the", "bound to the nfkappab", "to the nfkappab heterodimer", "nfkappab heterodimer on", "heterodimer on residues", "on residues s19 and", "residues s19 and s23", "and s23 step", "s23 step 45", "step 45 and", "45 and directs", "and directs nfkbia to", "directs nfkbia to 26s", "nfkbia to 26s proteasome", "to 26s proteasome degradation", "proteasome degradation step", "degradation step 47", "step 47 . the", "47 . the nfkappab", ". the nfkappab heterodimer", "the nfkappab heterodimer with", "nfkappab heterodimer with a", "heterodimer with a free", "with a free nts", "a free nts sequence", "free nts sequence finally", "nts sequence finally migrates", "sequence finally migrates to", "finally migrates to the", "migrates to the nucleus", "to the nucleus to", "the nucleus to regulate", "nucleus to regulate gene", "to regulate gene transcription", "gene transcription step", "transcription step 46", "changes in gene expression are", "in gene expression are required", "gene expression are required for", "expression are required for the", "are required for the t", "required for the t cell", "for the t cell to", "the t cell to gain", "t cell to gain full", "cell to gain full proliferative", "to gain full proliferative competence", "gain full proliferative competence and", "full proliferative competence and to", "proliferative competence and to produce", "competence and to produce effector", "and to produce effector cytokines.", "to produce effector cytokines. three", "produce effector cytokines. three transcription", "effector cytokines. three transcription factors", "cytokines. three transcription factors in", "three transcription factors in particular", "transcription factors in particular have", "factors in particular have been", "in particular have been found", "particular have been found to", "have been found to play", "been found to play a", "found to play a key", "to play a key role", "play a key role in", "a key role in tcr", "key role in tcr stimulated", "role in tcr stimulated changes", "in tcr stimulated changes in", "tcr stimulated changes in gene", "stimulated changes in gene expression", "in gene expression namely", "gene expression namely nfkappab", "namely nfkappab nfat and", "nfkappab nfat and ap", "nfat and ap 1. a", "and ap 1. a key", "ap 1. a key step", "1. a key step in", "a key step in nfkappab", "key step in nfkappab activation", "step in nfkappab activation is", "in nfkappab activation is the", "nfkappab activation is the stimulation", "activation is the stimulation and", "is the stimulation and translocation", "the stimulation and translocation of", "stimulation and translocation of prkcq.", "and translocation of prkcq. the", "translocation of prkcq. the critical", "of prkcq. the critical element", "prkcq. the critical element that", "the critical element that effects", "critical element that effects prkcq", "element that effects prkcq activation", "that effects prkcq activation is", "effects prkcq activation is pi3k.", "prkcq activation is pi3k. pi3k", "activation is pi3k. pi3k translocates", "is pi3k. pi3k translocates to", "pi3k. pi3k translocates to the", "pi3k translocates to the plasma", "translocates to the plasma membrane", "to the plasma membrane by", "the plasma membrane by interacting", "plasma membrane by interacting with", "membrane by interacting with phospho", "by interacting with phospho tyrosines", "interacting with phospho tyrosines on", "with phospho tyrosines on cd28", "phospho tyrosines on cd28 via", "tyrosines on cd28 via its", "on cd28 via its two", "cd28 via its two sh2", "via its two sh2 domains", "its two sh2 domains located", "two sh2 domains located in", "sh2 domains located in p85", "domains located in p85 subunit", "in p85 subunit step", "p85 subunit step 24", "subunit step 24 .", "step 24 . the p110", "24 . the p110 subunit", ". the p110 subunit of", "the p110 subunit of pi3k", "p110 subunit of pi3k phosphorylates", "subunit of pi3k phosphorylates the", "of pi3k phosphorylates the inositol", "pi3k phosphorylates the inositol ring", "phosphorylates the inositol ring of", "the inositol ring of pip2", "inositol ring of pip2 to", "ring of pip2 to generate", "of pip2 to generate pip3", "to generate pip3 steps", "generate pip3 steps 25", "pip3 steps 25 .", "steps 25 . the reverse", "25 . the reverse dephosphorylation", ". the reverse dephosphorylation process", "the reverse dephosphorylation process from", "reverse dephosphorylation process from pip3", "dephosphorylation process from pip3 to", "process from pip3 to pip2", "from pip3 to pip2 is", "pip3 to pip2 is catalysed", "to pip2 is catalysed by", "pip2 is catalysed by pten", "catalysed by pten step", "by pten step 27", "pten step 27 .", "step 27 . pip3 may", "27 . pip3 may also", ". pip3 may also be", "pip3 may also be dephosphorylated", "may also be dephosphorylated by", "also be dephosphorylated by the", "be dephosphorylated by the phosphatase", "dephosphorylated by the phosphatase ship", "by the phosphatase ship to", "the phosphatase ship to generate", "phosphatase ship to generate pi", "ship to generate pi 3", "to generate pi 3 4", "generate pi 3 4 p2", "3 4 p2 step", "4 p2 step 26", "p2 step 26 .", "step 26 . pip3 and", "26 . pip3 and pi", ". pip3 and pi 3", "pip3 and pi 3 4", "and pi 3 4 p2", "pi 3 4 p2 acts", "3 4 p2 acts as", "4 p2 acts as binding", "p2 acts as binding sites", "acts as binding sites to", "as binding sites to the", "binding sites to the ph", "sites to the ph domain", "to the ph domain of", "the ph domain of pdk1", "domain of pdk1 step", "of pdk1 step 28", "step 28 and akt", "and akt step 29", "akt step 29 .", "step 29 . pkb is", "29 . pkb is activated", ". pkb is activated in", "pkb is activated in response", "is activated in response to", "activated in response to pi3k", "in response to pi3k stimulation", "response to pi3k stimulation by", "to pi3k stimulation by pdk1", "stimulation by pdk1 step", "by pdk1 step 30", "pdk1 step 30 .", "step 30 . pdk1 has", "30 . pdk1 has an", ". pdk1 has an essential", "pdk1 has an essential role", "has an essential role in", "an essential role in regulating", "essential role in regulating the", "role in regulating the activation", "in regulating the activation of", "regulating the activation of prkcq", "the activation of prkcq and", "activation of prkcq and recruitment", "of prkcq and recruitment of", "prkcq and recruitment of cbm", "and recruitment of cbm complex", "recruitment of cbm complex to", "of cbm complex to the", "cbm complex to the immune", "complex to the immune synapse.", "to the immune synapse. prkcq", "the immune synapse. prkcq is", "immune synapse. prkcq is a", "synapse. prkcq is a member", "prkcq is a member of", "is a member of novel", "a member of novel class", "of novel class dag", "novel class dag dependent", "dag dependent ca++ independent", "ca++ independent of pkc", "independent of pkc and", "of pkc and the only", "pkc and the only member", "and the only member known", "the only member known to", "only member known to translocate", "member known to translocate to", "known to translocate to this", "to translocate to this synapse.", "translocate to this synapse. prior", "to this synapse. prior to", "this synapse. prior to tcr", "synapse. prior to tcr stimulation", "prior to tcr stimulation prkcq", "to tcr stimulation prkcq exists", "tcr stimulation prkcq exists in", "stimulation prkcq exists in an", "prkcq exists in an inactive", "exists in an inactive closed", "in an inactive closed conformation.", "an inactive closed conformation. tcr", "inactive closed conformation. tcr signals", "closed conformation. tcr signals stimulate", "conformation. tcr signals stimulate prkcq", "signals stimulate prkcq step", "stimulate prkcq step 31", "step 31 and release", "31 and release dag", "and release dag molecules. subsequently", "dag molecules. subsequently dag", "molecules. subsequently dag binds", "subsequently dag binds to", "dag binds to prkcq via", "binds to prkcq via the", "to prkcq via the c1", "prkcq via the c1 domain", "via the c1 domain and", "the c1 domain and undergoes", "c1 domain and undergoes phosphorylation", "domain and undergoes phosphorylation on", "and undergoes phosphorylation on tyrosine", "undergoes phosphorylation on tyrosine 90", "phosphorylation on tyrosine 90 by", "on tyrosine 90 by lck", "tyrosine 90 by lck to", "90 by lck to attain", "by lck to attain an", "lck to attain an open", "to attain an open conformation", "an open conformation step", "open conformation step 32", "conformation step 32 .", "step 32 . prkcq is", "32 . prkcq is further", ". prkcq is further phosphorylated", "prkcq is further phosphorylated by", "is further phosphorylated by pdk1", "further phosphorylated by pdk1 on", "phosphorylated by pdk1 on threonine", "by pdk1 on threonine 538", "on threonine 538 step", "threonine 538 step 33", "538 step 33 .", "step 33 . this step", "33 . this step is", ". this step is critical", "this step is critical for", "step is critical for pkc", "is critical for pkc activity.", "critical for pkc activity. carma1", "for pkc activity. carma1 translocates", "pkc activity. carma1 translocates to", "activity. carma1 translocates to the", "carma1 translocates to the plasma", "to the plasma membrane following", "the plasma membrane following the", "plasma membrane following the interaction", "membrane following the interaction of", "following the interaction of its", "the interaction of its sh3", "interaction of its sh3 domain", "of its sh3 domain with", "its sh3 domain with the", "sh3 domain with the 'pxxp'", "domain with the 'pxxp' motif", "with the 'pxxp' motif on", "the 'pxxp' motif on pdk1", "motif on pdk1 step", "on pdk1 step 34", "pdk1 step 34 .", "step 34 . carma1 is", "34 . carma1 is phosphorylated", ". carma1 is phosphorylated by", "carma1 is phosphorylated by pkc", "is phosphorylated by pkc theta", "phosphorylated by pkc theta on", "by pkc theta on residue", "pkc theta on residue s552", "on residue s552 step", "residue s552 step 35", "step 35 leading", "35 leading to", "leading to the oligomerization of", "to the oligomerization of carma1.", "the oligomerization of carma1. this", "oligomerization of carma1. this complex", "of carma1. this complex acts", "carma1. this complex acts as", "this complex acts as a", "complex acts as a scaffold", "as a scaffold recruiting", "a scaffold recruiting bcl10", "scaffold recruiting bcl10 to", "recruiting bcl10 to the synapse", "bcl10 to the synapse by", "to the synapse by interacting", "the synapse by interacting with", "synapse by interacting with their", "by interacting with their card", "interacting with their card domains", "their card domains step", "card domains step 36", "domains step 36 .", "step 36 . bcl10 undergoes", "36 . bcl10 undergoes phosphorylation", ". bcl10 undergoes phosphorylation mediated", "bcl10 undergoes phosphorylation mediated by", "undergoes phosphorylation mediated by the", "phosphorylation mediated by the enzyme", "mediated by the enzyme rip2", "the enzyme rip2 step", "enzyme rip2 step 37", "rip2 step 37 .", "step 37 . activated bcl10", "37 . activated bcl10 then", ". activated bcl10 then mediates", "activated bcl10 then mediates the", "bcl10 then mediates the ubiquitination", "then mediates the ubiquitination of", "mediates the ubiquitination of ikbkg", "the ubiquitination of ikbkg by", "ubiquitination of ikbkg by recruiting", "of ikbkg by recruiting malt1", "ikbkg by recruiting malt1 and", "by recruiting malt1 and traf6.", "recruiting malt1 and traf6. malt1", "malt1 and traf6. malt1 binds", "and traf6. malt1 binds to", "traf6. malt1 binds to bcl10", "malt1 binds to bcl10 with", "binds to bcl10 with its", "to bcl10 with its ig", "bcl10 with its ig like", "with its ig like domains", "its ig like domains and", "ig like domains and undergoes", "like domains and undergoes oligomerization", "and undergoes oligomerization step", "undergoes oligomerization step 38", "oligomerization step 38 .", "step 38 . traf6 binds", "38 . traf6 binds to", ". traf6 binds to the", "traf6 binds to the oligomerized", "binds to the oligomerized malt1", "to the oligomerized malt1 and", "the oligomerized malt1 and also", "oligomerized malt1 and also undergoes", "malt1 and also undergoes oligomerization", "also undergoes oligomerization step", "undergoes oligomerization step 39", "oligomerization step 39 .", "step 39 . oligomerized traf6", "39 . oligomerized traf6 acts", ". oligomerized traf6 acts as", "oligomerized traf6 acts as a", "traf6 acts as a ubiquitin", "acts as a ubiquitin protein", "as a ubiquitin protein ligase", "ubiquitin protein ligase catalyzing", "protein ligase catalyzing auto", "ligase catalyzing auto k63", "catalyzing auto k63 linked polyubiquitination", "k63 linked polyubiquitination step", "linked polyubiquitination step 40", "polyubiquitination step 40 .", "step 40 . this k", "40 . this k 63", ". this k 63 ubiquitinated", "this k 63 ubiquitinated traf6", "k 63 ubiquitinated traf6 activates", "63 ubiquitinated traf6 activates map3k7", "ubiquitinated traf6 activates map3k7 kinase", "traf6 activates map3k7 kinase bound", "activates map3k7 kinase bound to", "map3k7 kinase bound to tab2", "bound to tab2 step", "to tab2 step 41", "step 41 and also", "41 and also ubiquitinates", "and also ubiquitinates ikbkg in", "also ubiquitinates ikbkg in the", "ubiquitinates ikbkg in the ikk", "ikbkg in the ikk complex", "the ikk complex step", "ikk complex step 44", "complex step 44 .", "step 44 . map3k7 undergoes", "44 . map3k7 undergoes autophosphorylation", ". map3k7 undergoes autophosphorylation on", "map3k7 undergoes autophosphorylation on residues", "undergoes autophosphorylation on residues t184", "autophosphorylation on residues t184 and", "on residues t184 and t187", "residues t184 and t187 and", "t184 and t187 and gets", "and t187 and gets activated", "and gets activated step", "gets activated step 42", "activated step 42 .", "step 42 . activated map3k7", "42 . activated map3k7 kinase", ". activated map3k7 kinase phosphorylates", "activated map3k7 kinase phosphorylates ikbkb", "map3k7 kinase phosphorylates ikbkb on", "kinase phosphorylates ikbkb on residues", "phosphorylates ikbkb on residues s177", "ikbkb on residues s177 and", "on residues s177 and s181", "residues s177 and s181 in", "s177 and s181 in the", "and s181 in the activation", "s181 in the activation loop", "in the activation loop and", "the activation loop and activates", "activation loop and activates the", "loop and activates the ikk", "and activates the ikk kinase", "activates the ikk kinase activity", "ikk kinase activity step", "kinase activity step 43", "activity step 43 .", "step 43 . ikbkb phosphorylates", "43 . ikbkb phosphorylates the", ". ikbkb phosphorylates the nfkbia", "ikbkb phosphorylates the nfkbia bound", "phosphorylates the nfkbia bound to", "the nfkbia bound to the", "nfkbia bound to the nfkappab", "bound to the nfkappab heterodimer", "the nfkappab heterodimer on", "nfkappab heterodimer on residues", "heterodimer on residues s19", "on residues s19 and s23", "s19 and s23 step", "and s23 step 45", "step 45 and directs", "45 and directs nfkbia", "and directs nfkbia to 26s", "directs nfkbia to 26s proteasome", "nfkbia to 26s proteasome degradation", "26s proteasome degradation step", "proteasome degradation step 47", "degradation step 47 .", "step 47 . the nfkappab", "47 . the nfkappab heterodimer", ". the nfkappab heterodimer with", "the nfkappab heterodimer with a", "nfkappab heterodimer with a free", "heterodimer with a free nts", "with a free nts sequence", "a free nts sequence finally", "free nts sequence finally migrates", "nts sequence finally migrates to", "sequence finally migrates to the", "finally migrates to the nucleus", "migrates to the nucleus to", "to the nucleus to regulate", "the nucleus to regulate gene", "nucleus to regulate gene transcription", "regulate gene transcription step", "gene transcription step 46", "transcription step 46 ." ] }, { "record_id": "GLY_000594_1_190", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "202430", "r hsa", "hsa 202430", "r hsa 202430" ] }, { "record_id": "GLY_000594_1_190", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translocation of", "of zap", "zap 70", "70 to", "to immunological", "immunological synapse", "translocation of zap", "of zap 70", "zap 70 to", "70 to immunological", "to immunological synapse", "translocation of zap 70", "of zap 70 to", "zap 70 to immunological", "70 to immunological synapse", "translocation of zap 70 to", "of zap 70 to immunological", "zap 70 to immunological synapse", "the dual", "dual phosphorylated", "phosphorylated itams", "itams recruit", "recruit syk", "syk kinase", "kinase zap70", "zap70 via", "via their", "their tandem", "tandem sh2", "sh2 domains", "step 8", "8 .", ". zap70", "zap70 subsequently", "subsequently undergoes", "undergoes phosphorylation", "phosphorylation on", "on multiple", "multiple tyrosine", "tyrosine residues", "residues for", "for further", "further activation.", "activation. zap70", "zap70 includes", "includes both", "both positive", "positive and", "and negative", "negative regulatory", "regulatory sites.", "sites. tyrosine", "tyrosine 493", "493 is", "is a", "a conserved", "conserved regulatory", "regulatory site", "site found", "found within", "within the", "the activation", "activation loop", "loop of", "of the", "the kinase", "kinase domain.", "domain. this", "this site", "site has", "has shown", "shown to", "to be", "be a", "a positive", "positive regulatory", "site required", "required for", "for zap70", "zap70 kinase", "kinase activity", "activity and", "and is", "is phosphorylated", "phosphorylated by", "by lck", "step 9", "9 .", ". this", "this phosphorylation", "phosphorylation contributes", "contributes to", "to the", "the active", "active conformation", "conformation of", "the catalytic", "catalytic domain.", "domain. later", "later zap70", "zap70 undergoes", "undergoes trans", "trans autophosphorylation", "autophosphorylation at", "at y315", "y315 and", "and y319", "step 10", "10 .", ". these", "these sites", "sites appear", "appear to", "be positive", "sites. zap70", "zap70 achieves", "achieves its", "its full", "full activation", "activation after", "after the", "the trans", "trans autophosphorylation.", "autophosphorylation. activated", "activated zap70", "zap70 along", "along with", "with lck", "lck phosphorylates", "phosphorylates the", "the multiple", "residues in", "in the", "the adaptor", "adaptor protein", "protein lat", "step 11", "11 .", ". ptpn22", "ptpn22 can", "can dephosphorylate", "dephosphorylate and", "and inhibit", "inhibit zap70", "zap70 activity", "activity to", "to downregulate", "downregulate tcr", "tcr signaling", "step 12", "12 .", "the dual phosphorylated", "dual phosphorylated itams", "phosphorylated itams recruit", "itams recruit syk", "recruit syk kinase", "syk kinase zap70", "kinase zap70 via", "zap70 via their", "via their tandem", "their tandem sh2", "tandem sh2 domains", "domains step", "step 8 .", "8 . zap70", ". zap70 subsequently", "zap70 subsequently undergoes", "subsequently undergoes phosphorylation", "undergoes phosphorylation on", "phosphorylation on multiple", "on multiple tyrosine", "multiple tyrosine residues", "tyrosine residues for", "residues for further", "for further activation.", "further activation. zap70", "activation. zap70 includes", "zap70 includes both", "includes both positive", "both positive and", "positive and negative", "and negative regulatory", "negative regulatory sites.", "regulatory sites. tyrosine", "sites. tyrosine 493", "tyrosine 493 is", "493 is a", "is a conserved", "a conserved regulatory", "conserved regulatory site", "regulatory site found", "site found within", "found within the", "within the activation", "the activation loop", "activation loop of", "loop of the", "of the kinase", "the kinase domain.", "kinase domain. this", "domain. this site", "this site has", "site has shown", "has shown to", "shown to be", "to be a", "be a positive", "a positive regulatory", "positive regulatory site", "regulatory site required", "site required for", "required for zap70", "for zap70 kinase", "zap70 kinase activity", "kinase activity and", "activity and is", "and is phosphorylated", "is phosphorylated by", "phosphorylated by lck", "lck step", "step 9 .", "9 . this", ". this phosphorylation", "this phosphorylation contributes", "phosphorylation contributes to", "contributes to the", "to the active", "the active conformation", "active conformation of", "conformation of the", "of the catalytic", "the catalytic domain.", "catalytic domain. later", "domain. later zap70", "later zap70 undergoes", "zap70 undergoes trans", "undergoes trans autophosphorylation", "trans autophosphorylation at", "autophosphorylation at y315", "at y315 and", "y315 and y319", "y319 step", "step 10 .", "10 . these", ". these sites", "these sites appear", "sites appear to", "appear to be", "to be positive", "be positive regulatory", "positive regulatory sites.", "regulatory sites. zap70", "sites. zap70 achieves", "zap70 achieves its", "achieves its full", "its full activation", "full activation after", "activation after the", "after the trans", "the trans autophosphorylation.", "trans autophosphorylation. activated", "autophosphorylation. activated zap70", "activated zap70 along", "zap70 along with", "along with lck", "with lck phosphorylates", "lck phosphorylates the", "phosphorylates the multiple", "the multiple tyrosine", "tyrosine residues in", "residues in the", "in the adaptor", "the adaptor protein", "adaptor protein lat", "lat step", "step 11 .", "11 . ptpn22", ". ptpn22 can", "ptpn22 can dephosphorylate", "can dephosphorylate and", "dephosphorylate and inhibit", "and inhibit zap70", "inhibit zap70 activity", "zap70 activity to", "activity to downregulate", "to downregulate tcr", "downregulate tcr signaling", "signaling step", "step 12 .", "the dual phosphorylated itams", "dual phosphorylated itams recruit", "phosphorylated itams recruit syk", "itams recruit syk kinase", "recruit syk kinase zap70", "syk kinase zap70 via", "kinase zap70 via their", "zap70 via their tandem", "via their tandem sh2", "their tandem sh2 domains", "sh2 domains step", "domains step 8", "step 8 . zap70", "8 . zap70 subsequently", ". zap70 subsequently undergoes", "zap70 subsequently undergoes phosphorylation", "subsequently undergoes phosphorylation on", "undergoes phosphorylation on multiple", "phosphorylation on multiple tyrosine", "on multiple tyrosine residues", "multiple tyrosine residues for", "tyrosine residues for further", "residues for further activation.", "for further activation. zap70", "further activation. zap70 includes", "activation. zap70 includes both", "zap70 includes both positive", "includes both positive and", "both positive and negative", "positive and negative regulatory", "and negative regulatory sites.", "negative regulatory sites. tyrosine", "regulatory sites. tyrosine 493", "sites. tyrosine 493 is", "tyrosine 493 is a", "493 is a conserved", "is a conserved regulatory", "a conserved regulatory site", "conserved regulatory site found", "regulatory site found within", "site found within the", "found within the activation", "within the activation loop", "the activation loop of", "activation loop of the", "loop of the kinase", "of the kinase domain.", "the kinase domain. this", "kinase domain. this site", "domain. this site has", "this site has shown", "site has shown to", "has shown to be", "shown to be a", "to be a positive", "be a positive regulatory", "a positive regulatory site", "positive regulatory site required", "regulatory site required for", "site required for zap70", "required for zap70 kinase", "for zap70 kinase activity", "zap70 kinase activity and", "kinase activity and is", "activity and is phosphorylated", "and is phosphorylated by", "is phosphorylated by lck", "by lck step", "lck step 9", "step 9 . this", "9 . this phosphorylation", ". this phosphorylation contributes", "this phosphorylation contributes to", "phosphorylation contributes to the", "contributes to the active", "to the active conformation", "the active conformation of", "active conformation of the", "conformation of the catalytic", "of the catalytic domain.", "the catalytic domain. later", "catalytic domain. later zap70", "domain. later zap70 undergoes", "later zap70 undergoes trans", "zap70 undergoes trans autophosphorylation", "undergoes trans autophosphorylation at", "trans autophosphorylation at y315", "autophosphorylation at y315 and", "at y315 and y319", "and y319 step", "y319 step 10", "step 10 . these", "10 . these sites", ". these sites appear", "these sites appear to", "sites appear to be", "appear to be positive", "to be positive regulatory", "be positive regulatory sites.", "positive regulatory sites. zap70", "regulatory sites. zap70 achieves", "sites. zap70 achieves its", "zap70 achieves its full", "achieves its full activation", "its full activation after", "full activation after the", "activation after the trans", "after the trans autophosphorylation.", "the trans autophosphorylation. activated", "trans autophosphorylation. activated zap70", "autophosphorylation. activated zap70 along", "activated zap70 along with", "zap70 along with lck", "along with lck phosphorylates", "with lck phosphorylates the", "lck phosphorylates the multiple", "phosphorylates the multiple tyrosine", "the multiple tyrosine residues", "multiple tyrosine residues in", "tyrosine residues in the", "residues in the adaptor", "in the adaptor protein", "the adaptor protein lat", "protein lat step", "lat step 11", "step 11 . ptpn22", "11 . ptpn22 can", ". ptpn22 can dephosphorylate", "ptpn22 can dephosphorylate and", "can dephosphorylate and inhibit", "dephosphorylate and inhibit zap70", "and inhibit zap70 activity", "inhibit zap70 activity to", "zap70 activity to downregulate", "activity to downregulate tcr", "to downregulate tcr signaling", "tcr signaling step", "signaling step 12", "the dual phosphorylated itams recruit", "dual phosphorylated itams recruit syk", "phosphorylated itams recruit syk kinase", "itams recruit syk kinase zap70", "recruit syk kinase zap70 via", "syk kinase zap70 via their", "kinase zap70 via their tandem", "zap70 via their tandem sh2", "via their tandem sh2 domains", "tandem sh2 domains step", "sh2 domains step 8", "domains step 8 .", "step 8 . zap70 subsequently", "8 . zap70 subsequently undergoes", ". zap70 subsequently undergoes phosphorylation", "zap70 subsequently undergoes phosphorylation on", "subsequently undergoes phosphorylation on multiple", "undergoes phosphorylation on multiple tyrosine", "phosphorylation on multiple tyrosine residues", "on multiple tyrosine residues for", "multiple tyrosine residues for further", "tyrosine residues for further activation.", "residues for further activation. zap70", "for further activation. zap70 includes", "further activation. zap70 includes both", "activation. zap70 includes both positive", "zap70 includes both positive and", "includes both positive and negative", "both positive and negative regulatory", "positive and negative regulatory sites.", "and negative regulatory sites. tyrosine", "negative regulatory sites. tyrosine 493", "regulatory sites. tyrosine 493 is", "sites. tyrosine 493 is a", "tyrosine 493 is a conserved", "493 is a conserved regulatory", "is a conserved regulatory site", "a conserved regulatory site found", "conserved regulatory site found within", "regulatory site found within the", "site found within the activation", "found within the activation loop", "within the activation loop of", "the activation loop of the", "activation loop of the kinase", "loop of the kinase domain.", "of the kinase domain. this", "the kinase domain. this site", "kinase domain. this site has", "domain. this site has shown", "this site has shown to", "site has shown to be", "has shown to be a", "shown to be a positive", "to be a positive regulatory", "be a positive regulatory site", "a positive regulatory site required", "positive regulatory site required for", "regulatory site required for zap70", "site required for zap70 kinase", "required for zap70 kinase activity", "for zap70 kinase activity and", "zap70 kinase activity and is", "kinase activity and is phosphorylated", "activity and is phosphorylated by", "and is phosphorylated by lck", "phosphorylated by lck step", "by lck step 9", "lck step 9 .", "step 9 . this phosphorylation", "9 . this phosphorylation contributes", ". this phosphorylation contributes to", "this phosphorylation contributes to the", "phosphorylation contributes to the active", "contributes to the active conformation", "to the active conformation of", "the active conformation of the", "active conformation of the catalytic", "conformation of the catalytic domain.", "of the catalytic domain. later", "the catalytic domain. later zap70", "catalytic domain. later zap70 undergoes", "domain. later zap70 undergoes trans", "later zap70 undergoes trans autophosphorylation", "zap70 undergoes trans autophosphorylation at", "undergoes trans autophosphorylation at y315", "trans autophosphorylation at y315 and", "autophosphorylation at y315 and y319", "y315 and y319 step", "and y319 step 10", "y319 step 10 .", "step 10 . these sites", "10 . these sites appear", ". these sites appear to", "these sites appear to be", "sites appear to be positive", "appear to be positive regulatory", "to be positive regulatory sites.", "be positive regulatory sites. zap70", "positive regulatory sites. zap70 achieves", "regulatory sites. zap70 achieves its", "sites. zap70 achieves its full", "zap70 achieves its full activation", "achieves its full activation after", "its full activation after the", "full activation after the trans", "activation after the trans 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in", "yorkie .

in their", ".

in their unphosphorylated", "their unphosphorylated states", "states yap1", "and wwtr1 freely", "wwtr1 freely enter", "freely enter the", "enter the nucleus", "the nucleus and", "nucleus and function", "and function as", "function as transcriptional", "as transcriptional co", "transcriptional co activators.", "co activators. in", "activators. in their", "in their phosphorylated", "their phosphorylated states", "states however", "however yap1", "and wwtr1 are", "wwtr1 are instead", "are instead bound", "instead bound by", "bound by 14", "by 14 3", "14 3 3", "3 3 proteins", "proteins ywhab", "ywhab and ywhae", "and ywhae respectively", "respectively and", "and sequestered in", "sequestered in the", "in the cytosol.

several", "the cytosol.

several accessory", "cytosol.

several accessory proteins", "accessory proteins are", "proteins are required", "are required for", "required for the", "for the three", "the three step", "step kinase cascade", "kinase cascade to", "cascade to function.", "to function. stk3", "mst1 each", "each form a", "form a complex", "a complex with", "complex with sav1", "sav1 homologue", "homologue of drosophila", "of drosophila salvador", "and lats1 and", "and lats2 form", "lats2 form complexes", "form complexes with", "complexes with mob1a", "with mob1a and", "drosophila mats .

in", "mats .

in drosophila", ".

in drosophila a", "drosophila a complex", "a complex of", "complex of three", "of three proteins", "proteins kibra", "kibra expanded", "expanded and", "merlin can", "can trigger the", "trigger the hippo", "the hippo cascade.", "hippo cascade. a", "cascade. a human", "a human homologue", "human homologue of", "homologue of kibra", "kibra wwc1", "wwc1 has", "has been identified", "identified and indirect", "and indirect evidence", "indirect evidence suggests", "evidence suggests that", "suggests that it", "that it can", "it can regulate", "can regulate the", "regulate the human", "the human hippo", "human hippo pathway", "pathway xiao", "xiao et al.", "et al. 2011", "al. 2011 .", "2011 . a", ". a molecular", "a molecular mechanism", "molecular mechanism for", "mechanism for this", "for this interaction", "this interaction has", "interaction has not", "has not yet", "not yet been", "yet been worked", "been worked out", "worked out and", "out and the", "and the molecular", "the molecular steps", "molecular steps that", "steps that trigger", "that trigger the", "the hippo kinase", "hippo kinase cascade", "kinase cascade in", "cascade in humans", "in humans are", "humans are unknown.

four", "are unknown.

four additional", "unknown.

four additional processes", "additional processes related", "processes related to", "related to human", "to human hippo", "signaling although", "although incompletely characterized", "characterized have", "have been described", "been described in", "described in sufficient", "in sufficient detail", "sufficient detail to", "detail to allow", "to allow their", "allow their annotation.", "their annotation. all", "annotation. all are", "all are of", "are of physiological", "of physiological interest", "physiological interest as", "interest as they", "as they are", "they are likely", "are likely to", "likely to be", "to be parts", "be parts of", "parts of mechanisms", "of mechanisms by", "mechanisms by which", "by which hippo", "which hippo signaling", "signaling is modulated", "is modulated or", "modulated or functionally", "or functionally linked", "functionally linked to", "linked to other", "to other signaling", "other signaling processes.", "signaling processes. first", "first the", "the caspase 3", "caspase 3 protease", "3 protease cleaves", "protease cleaves stk3", "releasing inhibitory carboxyterminal", "inhibitory carboxyterminal domains", "carboxyterminal domains in", "domains in each", "in each case", "case leading", "leading to increased", "to increased kinase", "increased kinase activity", "kinase activity and", "activity and yap1", "and yap1 /", "yap1 / taz", "/ taz phosphorylation", "phosphorylation lee", "lee et al.", "et al. 2001", "al. 2001 .", "2001 . second", "second cytosolic", "amot angiomotin", "angiomotin proteins", "proteins can bind", "can bind yap1", "bind yap1 and", "taz in", "in their unphosphorylated", "states a", "a process that", "process that may", "that may provide", "may provide a", "provide a hippo", "a hippo independent", "hippo independent mechanism", "independent mechanism to", "mechanism to down", "to down regulate", "down regulate the", "regulate the activities", "the activities of", "activities of these", "of these proteins", "proteins chan", "chan et al.", "2011 . third", "third wwtr1", "taz and", "and yap1 bind", "yap1 bind zo", "bind zo 1", "zo 1 and", "1 and 2", "and 2 proteins", "proteins remue", "remue et al.", "2010 oka", "oka et al.", "2010 . fourth", "fourth phosphorylated", "taz binds", "binds and sequesters", "and sequesters dvl2", "dvl2 providing", "providing a molecular", "a molecular link", "molecular link between", "link between hippo", "between hippo and", "hippo and wnt", "and wnt signaling", "signaling varelas", "varelas et al.", "human hippo signaling is", "hippo signaling is a", "signaling is a network", "is a network of", "a network of reactions", "network of reactions that", "of reactions that regulates", "reactions that regulates cell", "that regulates cell proliferation", "regulates cell proliferation and", "cell proliferation and apoptosis", "and apoptosis centered", "apoptosis centered on", "centered on a three", "on a three step", "a three step kinase", "three step kinase cascade.", "step kinase cascade. the", "kinase cascade. the cascade", "cascade. the cascade was", "the cascade was discovered", "cascade was discovered by", "was discovered by analysis", "discovered by analysis of", "by analysis of drosophila", "analysis of drosophila mutations", "of drosophila mutations that", "drosophila mutations that lead", "mutations that lead to", "that lead to tissue", "lead to tissue overgrowth", "tissue overgrowth and", "overgrowth and human", "and human homologues of", "human homologues of its", "homologues of its components", "of its components have", "its components have since", "components have since been", "have since been identified", "since been identified and", "been identified and characterized", "identified and characterized at", "and characterized at a", "characterized at a molecular", "at a molecular level.", "a molecular level. data", "molecular level. data from", "level. data from studies", "data from studies of", "from studies of mice", "studies of mice carrying", "of mice carrying knockout", "mice carrying knockout mutant", "carrying knockout mutant alleles", "knockout mutant alleles of", "mutant alleles of the", "alleles of the genes", "of the genes as", "the genes as well", "genes as well as", "as well as from", "well as from studies", "as from studies of", "from studies of somatic", "studies of somatic mutations", "of somatic mutations in", "somatic mutations in these", "mutations in these genes", "in these genes in", "these genes in human", "genes in human tumors", "in human tumors are", "human tumors are consistent", "tumors are consistent with", "are consistent with the", "consistent with the conclusion", "with the conclusion that", "the conclusion that in", "conclusion that in mammals", "in mammals as", "mammals as in", "in flies the", "flies the hippo", "the hippo cascade is", "hippo cascade is required", "cascade is required for", "is required for normal", "required for normal regulation", "for normal regulation of", "normal regulation of cell", "regulation of cell proliferation", "of cell proliferation and", "cell proliferation and defects", "proliferation and defects in", "and defects in the", "defects in the pathway", "in the pathway are", "the pathway are associated", "pathway are associated with", "are associated with cell", "associated with cell overgrowth", "with cell overgrowth and", "cell overgrowth and tumorigenesis", "and tumorigenesis oh", "tumorigenesis oh and", "oh and irvine 2010", "irvine 2010 pan", "2010 pan 2010", "pan 2010 zhao", "2010 zhao et", "zhao et al. 2010", "et al. 2010 .", "al. 2010 . this", "2010 . this group", ". this group of", "this group of reactions", "group of reactions is", "of reactions is also", "reactions is also notable", "is also notable for", "also notable for its", "notable for its abundance", "for its abundance of", "its abundance of protein:protein", "abundance of protein:protein interactions", "of protein:protein interactions mediated", "protein:protein interactions mediated by", "interactions mediated by ww", "mediated by ww domains", "by ww domains and", "ww domains and ppxy", "domains and ppxy sequence", "and ppxy sequence motifs", "sequence motifs sudol", "motifs sudol and", "sudol and harvey 2010", "and harvey 2010 .

there", "harvey 2010 .

there are", "2010 .

there are two", ".

there are two human", "are two human homologues", "two human homologues of", "human homologues of each", "homologues of each of", "of each of the", "each of the three", "of the three drosophila", "the three drosophila kinases", "drosophila kinases whose", "kinases whose functions", "whose functions are well", "functions are well conserved:", "are well conserved: expression", "well conserved: expression of", "conserved: expression of human", "expression of human proteins", "of human proteins rescues", "human proteins rescues fly", "proteins rescues fly mutants.", "rescues fly mutants. the", "fly mutants. the two", "mutants. the two members", "the two members of", "two members of each", "members of each pair", "of each pair of", "each pair of human", "pair of human homologues", "of human homologues have", "human homologues have biochemically", "homologues have biochemically indistinguishable", "have biochemically indistinguishable functions.", "biochemically indistinguishable functions. autophosphorylated", "indistinguishable functions. autophosphorylated stk3", "autophosphorylated stk3 mst2", "mst2 and stk4", "and stk4 mst1", "mst1 homologues", "homologues of drosophila hippo", "drosophila hippo catalyze", "hippo catalyze the", "catalyze the phosphorylation and", "the phosphorylation and activation", "phosphorylation and activation of", "and activation of lats1", "activation of lats1 and", "of lats1 and lats2", "and lats2 homologues", "lats2 homologues of", "homologues of drosophila warts", "drosophila warts and", "warts and of", "and of the accessory", "of the accessory proteins", "the accessory proteins mob1a", "accessory proteins mob1a and", "proteins mob1a and mob1b", "and mob1b homologues", "mob1b homologues of", "homologues of drosophila mats", "of drosophila mats .", "drosophila mats . lats1", "mats . lats1 and", ". lats1 and lats2", "lats1 and lats2 in", "and lats2 in turn", "lats2 in turn catalyze", "in turn catalyze the", "turn catalyze the phosphorylation", "catalyze the phosphorylation of", "the phosphorylation of the", "phosphorylation of the transcriptional", "of the transcriptional co", "the transcriptional co activators", "transcriptional co activators yap1", "co activators yap1 and", "activators yap1 and wwtr1", "and wwtr1 taz", "taz homologues", "homologues of drosophila yorkie", "of drosophila yorkie .

in", "drosophila yorkie .

in their", "yorkie .

in their unphosphorylated", ".

in their unphosphorylated states", "unphosphorylated states yap1", "states yap1 and", "yap1 and wwtr1 freely", "and wwtr1 freely enter", "wwtr1 freely enter the", "freely enter the nucleus", "enter the nucleus and", "the nucleus and function", "nucleus and function as", "and function as transcriptional", "function as transcriptional co", "as transcriptional co activators.", "transcriptional co activators. in", "co activators. in their", "activators. in their phosphorylated", "in their phosphorylated states", "phosphorylated states however", "however yap1 and", "yap1 and wwtr1 are", "and wwtr1 are instead", "wwtr1 are instead bound", "are instead bound by", "instead bound by 14", "bound by 14 3", "by 14 3 3", "14 3 3 proteins", "3 proteins ywhab", "proteins ywhab and", "ywhab and ywhae respectively", "ywhae respectively and", "respectively and sequestered", "and sequestered in the", "sequestered in the cytosol.

several", "in the cytosol.

several accessory", "the cytosol.

several accessory proteins", "cytosol.

several accessory proteins are", "accessory proteins are required", "proteins are required for", "are required for the", "required for the three", "for the three step", "the three step kinase", "three step kinase cascade", "step kinase cascade to", "kinase cascade to function.", "cascade to function. stk3", "function. stk3 mst2", "mst1 each form", "each form a complex", "form a complex with", "a complex with sav1", "with sav1 homologue", "sav1 homologue of", "homologue of drosophila salvador", "salvador and", "and lats1 and lats2", "lats1 and lats2 form", "and lats2 form complexes", "lats2 form complexes with", "form complexes with mob1a", "complexes with mob1a and", "with mob1a and mob1b", "of drosophila mats .

in", "drosophila mats .

in drosophila", "mats .

in drosophila a", ".

in drosophila a complex", "drosophila a complex of", "a complex of three", "complex of three proteins", "three proteins kibra", "expanded and merlin", "and merlin can", "merlin can trigger", "can trigger the hippo", "trigger the hippo cascade.", "the hippo cascade. a", "hippo cascade. a human", "cascade. a human homologue", "a human homologue of", "human homologue of kibra", "of kibra wwc1", "wwc1 has been", "has been identified and", "been identified and indirect", "identified and indirect evidence", "and indirect evidence suggests", "indirect evidence suggests that", "evidence suggests that it", "suggests that it can", "that it can regulate", "it can regulate the", "can regulate the human", "regulate the human hippo", "the human hippo pathway", "hippo pathway xiao", "pathway xiao et", "xiao et al. 2011", "et al. 2011 .", "al. 2011 . a", "2011 . a molecular", ". a molecular mechanism", "a molecular mechanism for", "molecular mechanism for this", "mechanism for this interaction", "for this interaction has", "this interaction has not", "interaction has not yet", "has not yet been", "not yet been worked", "yet been worked out", "been worked out and", "worked out and the", "out and the molecular", "and the molecular steps", "the molecular steps that", "molecular steps that trigger", "steps that trigger the", "that trigger the hippo", "trigger the hippo kinase", "the hippo kinase cascade", "hippo kinase cascade in", "kinase cascade in humans", "cascade in humans are", "in humans are unknown.

four", "humans are unknown.

four additional", "are unknown.

four additional processes", "unknown.

four additional processes related", "additional processes related to", "processes related to human", "related to human hippo", "to human hippo signaling", "hippo signaling although", "signaling although incompletely", "incompletely characterized have", "characterized have been", "have been described in", "been described in sufficient", "described in sufficient detail", "in sufficient detail to", "sufficient detail to allow", "detail to allow their", "to allow their annotation.", "allow their annotation. all", "their annotation. all are", "annotation. all are of", "all are of physiological", "are of physiological interest", "of physiological interest as", "physiological interest as they", "interest as they are", "as they are likely", "they are likely to", "are likely to be", "likely to be parts", "to be parts of", "be parts of mechanisms", "parts of mechanisms by", "of mechanisms by which", "mechanisms by which hippo", "by which hippo signaling", "which hippo signaling is", "hippo signaling is modulated", "signaling is modulated or", "is modulated or functionally", "modulated or functionally linked", "or functionally linked to", "functionally linked to other", "linked to other signaling", "to other signaling processes.", "other signaling processes. first", "processes. first the", "first the caspase", "the caspase 3 protease", "caspase 3 protease cleaves", "3 protease cleaves stk3", "cleaves stk3 mst2", "mst1 releasing", "releasing inhibitory carboxyterminal domains", "inhibitory carboxyterminal domains in", "carboxyterminal domains in each", "domains in each case", "each case leading", "case leading to", "leading to increased kinase", "to increased kinase activity", "increased kinase activity and", "kinase activity and yap1", "activity and yap1 /", "and yap1 / taz", "yap1 / taz phosphorylation", "taz phosphorylation lee", "phosphorylation lee et", "lee et al. 2001", "et al. 2001 .", "al. 2001 . second", ". second cytosolic", "second cytosolic amot", "cytosolic amot angiomotin", "angiomotin proteins can", "proteins can bind yap1", "can bind yap1 and", "bind yap1 and wwtr1", "taz in their", "in their unphosphorylated states", "unphosphorylated states a", "states a process", "a process that may", "process that may provide", "that may provide a", "may provide a hippo", "provide a hippo independent", "a hippo independent mechanism", "hippo independent mechanism to", "independent mechanism to down", "mechanism to down regulate", "to down regulate the", "down regulate the activities", "regulate the activities of", "the activities of these", "activities of these proteins", "these proteins chan", "proteins chan et", "chan et al. 2011", "al. 2011 . third", ". third wwtr1", "taz and yap1", "and yap1 bind zo", "yap1 bind zo 1", "bind zo 1 and", "zo 1 and 2", "1 and 2 proteins", "2 proteins remue", "proteins remue et", "remue et al. 2010", "al. 2010 oka", "2010 oka et", "oka et al. 2010", "al. 2010 . fourth", ". fourth phosphorylated", "fourth phosphorylated wwtr1", "phosphorylated wwtr1 taz", "taz binds and", "binds and sequesters dvl2", "sequesters dvl2 providing", "dvl2 providing a", "providing a molecular link", "a molecular link between", "molecular link between hippo", "link between hippo and", "between hippo and wnt", "hippo and wnt signaling", "wnt signaling varelas", "signaling varelas et", "varelas et al. 2010", "human hippo signaling is a", "hippo signaling is a network", "signaling is a network of", "is a network of reactions", "a network of reactions that", "network of reactions that regulates", "of reactions that regulates cell", "reactions that regulates cell proliferation", "that regulates cell proliferation and", "regulates cell proliferation and apoptosis", "proliferation and apoptosis centered", "and apoptosis centered on", "apoptosis centered on a", "centered on a three step", "on a three step kinase", "a three step kinase cascade.", "three step kinase cascade. the", "step kinase cascade. the cascade", "kinase cascade. the cascade was", "cascade. the cascade was discovered", "the cascade was discovered by", "cascade was discovered by analysis", "was discovered by analysis of", "discovered by analysis of drosophila", "by analysis of drosophila mutations", "analysis of drosophila mutations that", "of drosophila mutations that lead", "drosophila mutations that lead to", "mutations that lead to tissue", "that lead to tissue overgrowth", "to tissue overgrowth and", "tissue overgrowth and human", "overgrowth and human homologues", "and human homologues of its", "human homologues of its components", "homologues of its components have", "of its components have since", "its components have since been", "components have since been identified", "have since been identified and", "since been identified and characterized", "been identified and characterized at", "identified and characterized at a", "and characterized at a molecular", "characterized at a molecular level.", "at a molecular level. data", "a molecular level. data from", "molecular level. data from studies", "level. data from studies of", "data from studies of mice", "from studies of mice carrying", "studies of mice carrying knockout", "of mice carrying knockout mutant", "mice carrying knockout mutant alleles", "carrying knockout mutant alleles of", "knockout mutant alleles of the", "mutant alleles of the genes", "alleles of the genes as", "of the genes as well", "the genes as well as", "genes as well as from", "as well as from studies", "well as from studies of", "as from studies of somatic", "from studies of somatic mutations", "studies of somatic mutations in", "of somatic mutations in these", "somatic mutations in these genes", "mutations in these genes in", "in these genes in human", "these genes in human tumors", "genes in human tumors are", "in human tumors are consistent", "human tumors are consistent with", "tumors are consistent with the", "are consistent with the conclusion", "consistent with the conclusion that", "with the conclusion that in", "the conclusion that in mammals", "that in mammals as", "in mammals as in", "mammals as in flies", "as in flies the", "in flies the hippo", "flies the hippo cascade", "the hippo cascade is required", "hippo cascade is required for", "cascade is required for normal", "is required for normal regulation", "required for normal regulation of", "for normal regulation of cell", "normal regulation of cell proliferation", "regulation of cell proliferation and", "of cell proliferation and defects", "cell proliferation and defects in", "proliferation and defects in the", "and defects in the pathway", "defects in the pathway are", "in the pathway are associated", "the pathway are associated with", "pathway are associated with cell", "are associated with cell overgrowth", "associated with cell overgrowth and", "with cell overgrowth and tumorigenesis", "overgrowth and tumorigenesis oh", "and tumorigenesis oh and", "tumorigenesis oh and irvine", "and irvine 2010 pan", "irvine 2010 pan 2010", "pan 2010 zhao et", "2010 zhao et al.", "zhao et al. 2010 .", "et al. 2010 . this", "al. 2010 . this group", "2010 . this group of", ". this group of reactions", "this group of reactions is", "group of reactions is also", "of reactions is also notable", "reactions is also notable for", "is also notable for its", "also notable for its abundance", "notable for its abundance of", "for its abundance of protein:protein", "its abundance of protein:protein interactions", "abundance of protein:protein interactions mediated", "of protein:protein interactions mediated by", "protein:protein interactions mediated by ww", "interactions mediated by ww domains", "mediated by ww domains and", "by ww domains and ppxy", "ww domains and ppxy sequence", "domains and ppxy sequence motifs", "ppxy sequence motifs sudol", "sequence motifs sudol and", "motifs sudol and harvey", "sudol and harvey 2010 .

there", "and harvey 2010 .

there are", "harvey 2010 .

there are two", "2010 .

there are two human", ".

there are two human homologues", "are two human homologues of", "two human homologues of each", "human homologues of each of", "homologues of each of the", "of each of the three", "each of the three drosophila", "of the three drosophila kinases", "three drosophila kinases whose", "drosophila kinases whose functions", "kinases whose functions are", "whose functions are well conserved:", "functions are well conserved: expression", "are well conserved: expression of", "well conserved: expression of human", "conserved: expression of human proteins", "expression of human proteins rescues", "of human proteins rescues fly", "human proteins rescues fly mutants.", "proteins rescues fly mutants. the", "rescues fly mutants. the two", "fly mutants. the two members", "mutants. the two members of", "the two members of each", "two members of each pair", "members of each pair of", "of each pair of human", "each pair of human homologues", "pair of human homologues have", "of human homologues have biochemically", "human homologues have biochemically indistinguishable", "homologues have biochemically indistinguishable functions.", "have biochemically indistinguishable functions. autophosphorylated", "biochemically indistinguishable functions. autophosphorylated stk3", "functions. autophosphorylated stk3 mst2", "stk3 mst2 and", "mst1 homologues of", "of drosophila hippo catalyze", "drosophila hippo catalyze the", "hippo catalyze the phosphorylation", "catalyze the phosphorylation and activation", "the phosphorylation and activation of", "phosphorylation and activation of lats1", "and activation of lats1 and", "activation of lats1 and lats2", "lats1 and lats2 homologues", "and lats2 homologues of", "lats2 homologues of drosophila", "of drosophila warts and", "drosophila warts and of", "warts and of the", "and of the accessory proteins", "of the accessory proteins mob1a", "the accessory proteins mob1a and", "accessory proteins mob1a and mob1b", "mob1a and mob1b homologues", "and mob1b homologues of", "mob1b homologues of drosophila", "homologues of drosophila mats .", "of drosophila mats . lats1", "drosophila mats . lats1 and", "mats . lats1 and lats2", ". lats1 and lats2 in", "lats1 and lats2 in turn", "and lats2 in turn catalyze", "lats2 in turn catalyze the", "in turn catalyze the phosphorylation", "turn catalyze the phosphorylation of", "catalyze the phosphorylation of the", "the phosphorylation of the transcriptional", "phosphorylation of the transcriptional co", "of the transcriptional co activators", "the transcriptional co activators yap1", "transcriptional co activators yap1 and", "co activators yap1 and wwtr1", "yap1 and wwtr1 taz", "taz homologues of", "homologues of drosophila yorkie .

in", "of drosophila yorkie .

in their", "drosophila yorkie .

in their unphosphorylated", "yorkie .

in their unphosphorylated states", "their unphosphorylated states yap1", "unphosphorylated states yap1 and", "states yap1 and wwtr1", "yap1 and wwtr1 freely enter", "and wwtr1 freely enter the", "wwtr1 freely enter the nucleus", "freely enter the nucleus and", "enter the nucleus and function", "the nucleus and function as", "nucleus and function as transcriptional", "and function as transcriptional co", "function as transcriptional co activators.", "as transcriptional co activators. in", "transcriptional co activators. in their", "co activators. in their phosphorylated", "activators. in their phosphorylated states", "their phosphorylated states however", "states however yap1", "however yap1 and wwtr1", "yap1 and wwtr1 are instead", "and wwtr1 are instead bound", "wwtr1 are instead bound by", "are instead bound by 14", "instead bound by 14 3", "bound by 14 3 3", "by 14 3 3 proteins", "3 3 proteins ywhab", "3 proteins ywhab and", "proteins ywhab and ywhae", "and ywhae respectively and", "ywhae respectively and sequestered", "respectively and sequestered in", "and sequestered in the cytosol.

several", "sequestered in the cytosol.

several accessory", "in the cytosol.

several accessory proteins", "the cytosol.

several accessory proteins are", "cytosol.

several accessory proteins are required", "accessory proteins are required for", "proteins are required for the", "are required for the three", "required for the three step", "for the three step kinase", "the three step kinase cascade", "three step kinase cascade to", "step kinase cascade to function.", "kinase cascade to function. stk3", "to function. stk3 mst2", "stk4 mst1 each", "mst1 each form a", "each form a complex with", "form a complex with sav1", "complex with sav1 homologue", "with sav1 homologue of", "sav1 homologue of drosophila", "drosophila salvador and", "salvador and lats1", "and lats1 and lats2 form", "lats1 and lats2 form complexes", "and lats2 form complexes with", "lats2 form complexes with mob1a", "form complexes with mob1a and", "complexes with mob1a and mob1b", "homologues of drosophila mats .

in", "of drosophila mats .

in drosophila", "drosophila mats .

in drosophila a", "mats .

in drosophila a complex", ".

in drosophila a complex of", "drosophila a complex of three", "a complex of three proteins", "of three proteins kibra", "proteins kibra expanded", "kibra expanded and", "and merlin can trigger", "merlin can trigger the", "can trigger the hippo cascade.", "trigger the hippo cascade. a", "the hippo cascade. a human", "hippo cascade. a human homologue", "cascade. a human homologue of", "a human homologue of kibra", "homologue of kibra wwc1", "kibra wwc1 has", "wwc1 has been identified", "has been identified and indirect", "been identified and indirect evidence", "identified and indirect evidence suggests", "and indirect evidence suggests that", "indirect evidence suggests that it", "evidence suggests that it can", "suggests that it can regulate", "that it can regulate the", "it can regulate the human", "can regulate the human hippo", "regulate the human hippo pathway", "human hippo pathway xiao", "hippo pathway xiao et", "pathway xiao et al.", "xiao et al. 2011 .", "et al. 2011 . a", "al. 2011 . a molecular", "2011 . a molecular mechanism", ". a molecular mechanism for", "a molecular mechanism for this", "molecular mechanism for this interaction", "mechanism for this interaction has", "for this interaction has not", "this interaction has not yet", "interaction has not yet been", "has not yet been worked", "not yet been worked out", "yet been worked out and", "been worked out and the", "worked out and the molecular", "out and the molecular steps", "and the molecular steps that", "the molecular steps that trigger", "molecular steps that trigger the", "steps that trigger the hippo", "that trigger the hippo kinase", "trigger the hippo kinase cascade", "the hippo kinase cascade in", "hippo kinase cascade in humans", "kinase cascade in humans are", "cascade in humans are unknown.

four", "in humans are unknown.

four additional", "humans are unknown.

four additional processes", "are unknown.

four additional processes related", "unknown.

four additional processes related to", "additional processes related to human", "processes related to human hippo", "related to human hippo signaling", "human hippo signaling although", "hippo signaling although incompletely", "signaling although incompletely characterized", "although incompletely characterized have", "incompletely characterized have been", "characterized have been described", "have been described in sufficient", "been described in sufficient detail", "described in sufficient detail to", "in sufficient detail to allow", "sufficient detail to allow their", "detail to allow their annotation.", "to allow their annotation. all", "allow their annotation. all are", "their annotation. all are of", "annotation. all are of physiological", "all are of physiological interest", "are of physiological interest as", "of physiological interest as they", "physiological interest as they are", "interest as they are likely", "as they are likely to", "they are likely to be", "are likely to be parts", "likely to be parts of", "to be parts of mechanisms", "be parts of mechanisms by", "parts of mechanisms by which", "of mechanisms by which hippo", "mechanisms by which hippo signaling", "by which hippo signaling is", "which hippo signaling is modulated", "hippo signaling is modulated or", "signaling is modulated or functionally", "is modulated or functionally linked", "modulated or functionally linked to", "or functionally linked to other", "functionally linked to other signaling", "linked to other signaling processes.", "to other signaling processes. first", "signaling processes. first the", "processes. first the caspase", "first the caspase 3", "the caspase 3 protease cleaves", "caspase 3 protease cleaves stk3", "protease cleaves stk3 mst2", "mst1 releasing inhibitory", "releasing inhibitory carboxyterminal domains in", "inhibitory carboxyterminal domains in each", "carboxyterminal domains in each case", "in each case leading", "each case leading to", "case leading to increased", "leading to increased kinase activity", "to increased kinase activity and", "increased kinase activity and yap1", "kinase activity and yap1 /", "activity and yap1 / taz", "and yap1 / taz phosphorylation", "/ taz phosphorylation lee", "taz phosphorylation lee et", "phosphorylation lee et al.", "lee et al. 2001 .", "et al. 2001 . second", "2001 . second cytosolic", ". second cytosolic amot", "amot angiomotin proteins", "angiomotin proteins can bind", "proteins can bind yap1 and", "can bind yap1 and wwtr1", "wwtr1 taz in", "taz in their unphosphorylated", "their unphosphorylated states a", "unphosphorylated states a process", "states a process that", "a process that may provide", "process that may provide a", "that may provide a hippo", "may provide a hippo independent", "provide a hippo independent mechanism", "a hippo independent mechanism to", "hippo independent mechanism to down", "independent mechanism to down regulate", "mechanism to down regulate the", "to down regulate the activities", "down regulate the activities of", "regulate the activities of these", "the activities of these proteins", "of these proteins chan", "these proteins chan et", "proteins chan et al.", "chan et al. 2011 .", "et al. 2011 . third", "2011 . third wwtr1", "third wwtr1 taz", "wwtr1 taz and", "taz and yap1 bind", "and yap1 bind zo 1", "yap1 bind zo 1 and", "bind zo 1 and 2", "zo 1 and 2 proteins", "and 2 proteins remue", "2 proteins remue et", "proteins remue et al.", "et al. 2010 oka", "al. 2010 oka et", "2010 oka et al.", "oka et al. 2010 .", "et al. 2010 . fourth", "2010 . fourth phosphorylated", ". fourth phosphorylated wwtr1", "wwtr1 taz binds", "taz binds and sequesters", "and sequesters dvl2 providing", "sequesters dvl2 providing a", "dvl2 providing a molecular", "providing a molecular link between", "a molecular link between hippo", "molecular link between hippo and", "link between hippo and wnt", "between hippo and wnt signaling", "and wnt signaling varelas", "wnt signaling varelas et", "signaling varelas et al.", "varelas et al. 2010 ." ] }, { "record_id": "GLY_000594_1_193", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2029481", "r hsa", "hsa 2029481", "r hsa 2029481" ] }, { "record_id": "GLY_000594_1_193", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fcgr activation", "cross linking", "linking of", "of fcgrs", "fcgrs with", "with igg", "igg coated", "coated immune", "immune complexes", "complexes results", "results in", "in tyrosine", "tyrosine phosphorylation", "phosphorylation of", "of the", "the immuno", "immuno tyrosine", "tyrosine activation", "activation motif", "the rececptor", "rececptor by", "by membrane", "membrane bound", "bound tyrosine", "tyrosine kinases", "kinases of", "the src", "src family.", "family. the", "the phosphorylated", "phosphorylated itam", "itam tyrosines", "tyrosines serve", "serve as", "as docking", "docking 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activated syk", "is unclear. activated syk then", "unclear. activated syk then transmits", "activated syk then transmits downstream", "syk then transmits downstream signals", "then transmits downstream signals leading", "transmits downstream signals leading to", "downstream signals leading to actin", "signals leading to actin polymerization", "leading to actin polymerization and", "to actin polymerization and particle", "actin polymerization and particle internalization." ] }, { "record_id": "GLY_000594_1_194", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2029482", "r hsa", "hsa 2029482", "r hsa 2029482" ] }, { "record_id": "GLY_000594_1_194", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of actin", "actin dynamics", "dynamics for", "for phagocytic", "phagocytic cup", "cup formation", "regulation of actin", "of actin dynamics", "actin dynamics for", "dynamics for 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with the phagocytic cup.", "with the phagocytic cup. these", "the phagocytic cup. these are", "phagocytic cup. these are formed", "cup. these are formed by", "these are formed by the", "are formed by the activity", "formed by the activity of", "by the activity of phosphoinositol", "the activity of phosphoinositol kinases", "activity of phosphoinositol kinases and", "of phosphoinositol kinases and phospholipases.", "phosphoinositol kinases and phospholipases. pi3k", "kinases and phospholipases. pi3k is", "and phospholipases. pi3k is has", "phospholipases. pi3k is has been", "pi3k is has been shown", "is has been shown to", "has been shown to accumulate", "been shown to accumulate at", "shown to accumulate at phagocytic", "to accumulate at phagocytic cups", "accumulate at phagocytic cups and", "at phagocytic cups and converts", "phagocytic cups and converts pi", "and converts pi 4", "converts pi 4 5", "pi 4 5 p2", "4 5 p2 to pi", "p2 to pi 3", "to pi 3 4", "pi 3 4 5", "3 4 5 p3. these", "4 5 p3. these phosphoinositides", "5 p3. these phosphoinositides are", "p3. these phosphoinositides are capable", "these phosphoinositides are capable of", "phosphoinositides are capable of binding", "are capable of binding and", "capable of binding and increasing", "of binding and increasing the", "binding and increasing the activity", "and increasing the activity of", "increasing the activity of proteins", "the activity of proteins that", "activity of proteins that regulate", "of proteins that regulate the", "proteins that regulate the actin", "that regulate the actin cytoskeleton.", "regulate the actin cytoskeleton. phospholipases", "the actin cytoskeleton. phospholipases are", "actin cytoskeleton. phospholipases are lipid", "cytoskeleton. phospholipases are lipid modifying", "phospholipases are lipid modifying enzymes", "are lipid modifying enzymes that", "lipid modifying enzymes that produce", "modifying enzymes that produce lipid", "enzymes that produce lipid mediators", "that produce lipid mediators such", "produce lipid mediators such as", "lipid mediators such as diacylglycerol", "such as diacylglycerol dag", "dag arachidonic acid", "acid aa and", "aa and ip3. phopsholipases", "ip3. phopsholipases pla plc", "phopsholipases pla plc and", "pla plc and pld", "plc and pld have been", "and pld have been shown", "pld have been shown to", "have been shown to be", "been shown to be involved", "shown to be involved in", "to be involved in antibody", "involved in antibody igg", "antibody igg mediated", "igg mediated phagocytosis. the", "mediated phagocytosis. the plc product", "phagocytosis. the plc product ip3", "the plc product ip3 stimulates", "plc product ip3 stimulates release", "product ip3 stimulates release of", "ip3 stimulates release of calcium", "stimulates release of calcium from", "release of calcium from the", "of calcium from the endoplasmic", "calcium from the endoplasmic reticulum.", "from the endoplasmic reticulum. this", "the endoplasmic reticulum. this ca+2", "endoplasmic reticulum. this ca+2 concentration", "reticulum. this ca+2 concentration increase", "this ca+2 concentration increase is", "ca+2 concentration increase is greatest", "concentration increase is greatest in", "increase is greatest in the", "is greatest in the cytoplasm", "greatest in the cytoplasm surrounding", "in the cytoplasm surrounding the", "the cytoplasm surrounding the phagocytic", "cytoplasm surrounding the phagocytic cup.", "surrounding the phagocytic cup. calcium", "the phagocytic cup. calcium is", "phagocytic cup. calcium is involved", "cup. calcium is involved in", "calcium is involved in the", "is involved in the various", "involved in the various stages", "in the various stages of", "the various stages of phagosome", "various stages of phagosome formation", "of phagosome formation including", "phagosome formation including phagocytic", "formation including phagocytic ingestion", "including phagocytic ingestion and phagosome", "phagocytic ingestion and phagosome maturation." ] }, { "record_id": "GLY_000594_1_196", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "203641", "r hsa", "hsa 203641", "r hsa 203641" ] }, { "record_id": "GLY_000594_1_196", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nostrin mediated", "mediated enos", "enos trafficking", "nostrin mediated enos", "mediated enos trafficking", "nostrin mediated enos trafficking", "enos traffic", "traffic inducer", "is a", "a novel", "novel 506", "506 amino", "amino acid", "acid enos", "enos interacting", "interacting protein.", "along with", "with a", "a decrease", "decrease in", "in enos", "enos activity", "nostrin causes", "causes translocation", "translocation of", "of enos", "enos from", "from the", "the plasma", "plasma membrane", "membrane to", "to intracellular", "intracellular vesicular", "vesicular structures.", "nostrin functions", "functions as", "as an", "an adaptor", "adaptor protein", "protein through", "through homotrimerization", "homotrimerization and", "and recruitment", "recruitment of", "dynamin 2", "and n", "n wasp", "wasp to", "to its", "its sh3", "sh3 domain.", "studies indicated", "indicated that", "that nostrin", "nostrin may", "may facilitate", "facilitate vesicle", "vesicle fission", "fission and", "and endocytosis", "endocytosis of", "enos by", "by coordinating", "coordinating the", "the function", "function of", "of dynamin", "dynamin and", "which in", "in turn", "recruits the", "the arp2/3", "arp2/3 complex", "initiating actin", "actin filament", "filament polymerization.", "this process", "process is", "is thought", "thought to", "to occur", "occur via", "via caveolar", "caveolar endocytosis.", "enos traffic inducer", "inducer nostrin", "nostrin is", "is a novel", "a novel 506", "novel 506 amino", "506 amino acid", "amino acid enos", "acid enos interacting", "enos interacting protein.", "protein. along", "along with a", "with a decrease", "a decrease in", "decrease in enos", "in enos activity", "activity nostrin", "nostrin causes translocation", "causes translocation of", "translocation of enos", "of enos from", "enos from the", "from the plasma", "the plasma membrane", "plasma membrane to", "membrane to intracellular", "to intracellular vesicular", "intracellular vesicular structures.", "structures. nostrin", "nostrin functions as", "functions as an", "as an adaptor", "an adaptor protein", "adaptor protein through", "protein through homotrimerization", "through homotrimerization and", "homotrimerization and recruitment", "and recruitment of", "recruitment of enos", "enos dynamin", "2 and", "and n wasp", "n wasp to", "wasp to its", "to its sh3", "its sh3 domain.", "domain. studies", "studies indicated that", "indicated that nostrin", "that nostrin may", "nostrin may facilitate", "may facilitate vesicle", "facilitate vesicle fission", "vesicle fission and", "fission and endocytosis", "and endocytosis 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", "traffic inducer nostrin", "nostrin is a", "is a novel 506", "a novel 506 amino", "novel 506 amino acid", "506 amino acid enos", "amino acid enos interacting", "acid enos interacting protein.", "interacting protein. along", "protein. along with", "along with a decrease", "with a decrease in", "a decrease in enos", "decrease in enos activity", "enos activity nostrin", "activity nostrin causes", "nostrin causes translocation of", "causes translocation of enos", "translocation of enos from", "of enos from the", "enos from the plasma", "from the plasma membrane", "the plasma membrane to", "plasma membrane to intracellular", "membrane to intracellular vesicular", "to intracellular vesicular structures.", "vesicular structures. nostrin", "structures. nostrin functions", "nostrin functions as an", "functions as an adaptor", "as an adaptor protein", "an adaptor protein through", "adaptor protein through homotrimerization", "protein through homotrimerization and", "through homotrimerization and recruitment", "homotrimerization and recruitment of", "and recruitment of enos", "of enos dynamin", "enos dynamin 2", "dynamin 2 and", "2 and n", "and n wasp to", "n wasp to its", "wasp to its sh3", "to its sh3 domain.", "sh3 domain. studies", "domain. studies indicated", "studies indicated that nostrin", "indicated that nostrin may", "that nostrin may facilitate", "nostrin may facilitate vesicle", "may facilitate vesicle fission", "facilitate vesicle fission and", "vesicle fission and endocytosis", "fission and endocytosis of", "and endocytosis of enos", "endocytosis of enos by", "of enos by coordinating", "enos by coordinating the", "by coordinating the function", "coordinating the function of", "the function of dynamin", "function of dynamin and", "of dynamin and n", "dynamin and n wasp", "n wasp which", "wasp which in", "in turn recruits", "turn recruits the", "recruits the arp2/3 complex", "arp2/3 complex initiating", "complex initiating actin", "initiating actin filament polymerization.", "filament polymerization. overall", "overall this process", "this process is thought", "process is thought to", "is thought to occur", "thought to occur via", "to occur via caveolar", "occur via caveolar endocytosis.", "caveolar endocytosis.



", "enos traffic inducer nostrin", "inducer nostrin is", "nostrin is a novel", "is a novel 506 amino", "a novel 506 amino acid", "novel 506 amino acid enos", "506 amino acid enos interacting", "amino acid enos interacting protein.", "enos interacting protein. along", "interacting protein. along with", "protein. along with a", "along with a decrease in", "with a decrease in enos", "a decrease in enos activity", "in enos activity nostrin", "enos activity nostrin causes", "activity nostrin causes translocation", "nostrin causes translocation of enos", "causes translocation of enos from", "translocation of enos from the", "of enos from the plasma", "enos from the plasma membrane", "from the plasma membrane to", "the plasma membrane to intracellular", "plasma membrane to intracellular vesicular", "membrane to intracellular vesicular structures.", "intracellular vesicular structures. nostrin", "vesicular structures. nostrin functions", "structures. nostrin functions as", "nostrin functions as an adaptor", "functions as an adaptor protein", "as an adaptor protein through", "an adaptor protein through homotrimerization", "adaptor protein through homotrimerization and", "protein through homotrimerization and recruitment", "through homotrimerization and recruitment of", "homotrimerization and recruitment of enos", "recruitment of enos dynamin", "of enos dynamin 2", "dynamin 2 and n", "2 and n wasp", "and n wasp to its", "n wasp to its sh3", "wasp to its sh3 domain.", "its sh3 domain. studies", "sh3 domain. studies indicated", "domain. studies indicated that", "studies indicated that nostrin may", "indicated that nostrin may facilitate", "that nostrin may facilitate vesicle", "nostrin may facilitate vesicle fission", "may facilitate vesicle fission and", "facilitate vesicle fission and endocytosis", "vesicle fission and endocytosis of", "fission and endocytosis of enos", "and endocytosis of enos by", "endocytosis of enos by coordinating", "of enos by coordinating the", "enos by coordinating the function", "by coordinating the function of", "coordinating the function of dynamin", "the function of dynamin and", "function of dynamin and n", "of dynamin and n wasp", "and n wasp which", "n wasp which in", "wasp which in turn", "which in turn recruits", "in turn recruits the", "turn recruits the arp2/3", "the arp2/3 complex initiating", "arp2/3 complex initiating actin", "complex initiating actin filament", "actin filament polymerization. overall", "polymerization. overall this", "overall this process is", "this process is thought to", "process is thought to occur", "is thought to occur via", "thought to occur via caveolar", "to occur via caveolar endocytosis.", "via caveolar endocytosis.



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phosphorylation", "by pyruvate", "dehydrogenase kinases", "pdk 1", "1 4", "and its", "its dephosphorylation", "dehydrogenase phosphate", "phosphate phosphatases", "pdp 1", "1 and", "and 2", "2 .", ". isoform", "isoform specific", "specific differences", "differences in", "in kinetic", "kinetic parameters", "and phosphorylation", "phosphorylation site", "site specificity", "specificity of", "of the", "the pdks", "pdks introduce", "introduce variations", "variations in", "in the", "the regulation", "of pdc", "pdc activity", "activity in", "in differing", "differing endocrine", "endocrine and", "and metabolic", "metabolic states", "sugden and", "and holness", "holness 2003", "2003 .", ". further", "pdh is", "is inhibited", "inhibited by", "by sirt4", "sirt4 and", "and the", "the drug", "drug dichloroacetic", "dichloroacetic acid", "dca .", "the mitochondrial pyruvate", "mitochondrial pyruvate dehydrogenase", "complex catalyzes the", "catalyzes the oxidative", "the oxidative 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phosphatases pdp 1", "phosphatases pdp 1 and", "pdp 1 and 2 .", "1 and 2 . isoform", "and 2 . isoform specific", "2 . isoform specific differences", ". isoform specific differences in", "isoform specific differences in kinetic", "specific differences in kinetic parameters", "in kinetic parameters regulation", "parameters regulation and", "regulation and phosphorylation site", "and phosphorylation site specificity of", "phosphorylation site specificity of the", "site specificity of the pdks", "specificity of the pdks introduce", "of the pdks introduce variations", "the pdks introduce variations in", "pdks introduce variations in the", "introduce variations in the regulation", "variations in the regulation of", "in the regulation of pdc", "the regulation of pdc activity", "regulation of pdc activity in", "of pdc activity in differing", "pdc activity in differing endocrine", "activity in differing endocrine and", "in differing endocrine and metabolic", "differing endocrine and metabolic 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}, { "record_id": "GLY_000594_1_201", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nf kb", "kb is", "is activated", "activated and", "and signals", "signals survival", "nf kb is", "kb is activated", "is activated and", "activated and signals", "and signals survival", "nf kb is activated", "kb is activated and", "is activated and signals", "activated and signals survival", "nf kb is activated and", "kb is activated and signals", "is activated and signals survival", "upon activation", "activation in", "in response", "response to", "to ngf", "kb moves", "moves to", "to the", "the nucleus", "where it", "it turns", "turns on", "on genes", "genes that", "that promote", "promote survival", "and triggers", "triggers the", "the expression", "expression of", "of hes1/5", "hes1/5 to", "to modulate", "modulate dendritic", "dendritic growth.", "upon activation in", "activation in response", "in response to", "response to ngf", "ngf nf", "nf kb moves", "kb 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the", "synaptic cleft.

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the", "plasma membrane.


the docked", "membrane.


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synaptic", "for release.


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cleft. postfusion", "cleft. postfusion the", "postfusion the synaptic", "vesicle membrane proteins", "proteins vamp2", "vamp2 rab3a", "rab3a vglut1", "vglut1 and", "synaptotagmin are", "are also found", "also found in", "found in the", "communication at the synapse", "at the synapse involves", "the synapse involves the", "synapse involves the release", "involves the release of", "the release of glutamate", "release of glutamate from", "of glutamate from the", "glutamate from the presynaptic", "from the presynaptic neuron", "the presynaptic neuron and", "presynaptic neuron and its", "neuron and its binding", "and its binding to", "its binding to glutamate", "binding to glutamate receptors", "to glutamate receptors on", "glutamate receptors on the", "receptors on the postsynaptic", "on the postsynaptic cell", "the postsynaptic cell to", "postsynaptic cell to generate", "cell to generate a", "to generate a series", "generate a series of", "a series of events", "series of events that", "of 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cleft.

the", "the synaptic cleft.

the glutamate", "synaptic cleft.

the glutamate life", "cleft.

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the", "the plasma membrane.


the docked", "plasma membrane.


the docked synaptic", "membrane.


the docked synaptic vesicle", "docked synaptic vesicle is", "synaptic vesicle is not", "vesicle is not ready", "is not ready for", "not ready for release", "ready for release until", "for release until it", "release until it undergoes", "until it undergoes molecular", "it undergoes molecular changes", "undergoes molecular changes to", "molecular changes to prime", "changes to prime it", "to prime it for", "prime it for fusion", "it for fusion with", "for fusion with the", "fusion with the plasma", "with the plasma membrane.", "the plasma membrane. munc13", "plasma membrane. munc13 is", "membrane. munc13 is one", "munc13 is one of", "is one of the", "one of the main", "of the main players", "the main players in", "main players in the", "players in the priming", "in the priming process.", "the priming process. munc", "priming process. munc 13", "process. munc 13 interacts", "munc 13 interacts with", "13 interacts with rim", "with rim rab3a", "rim rab3a interacting", "interacting molecule located", "molecule located in", "in the synaptic vesicle.", "the synaptic vesicle. munc", "synaptic vesicle. munc 13", "vesicle. munc 13 also", "munc 13 also interacts", "13 also interacts with", "also interacts with doc2.", "interacts with doc2. the", "with doc2. the precise", "doc2. the precise molecular", "the precise molecular mechanisms", "precise molecular mechanisms of", "molecular mechanisms of the", "mechanisms of the interactions", "of the interactions that", "the interactions that result", "interactions that result in", "that result in docking", "result in docking versus", "in docking versus priming", "docking versus priming are", "versus priming are not", "priming are not clear", "are not clear and", "not clear and the", "clear and the docking", "and the docking and", "the docking and priming", "docking and priming process", "and priming process have", "priming process have been", "process have been combined", "have been combined in", "been combined in this", "combined in this annotation", "in this annotation of", "this annotation of this", "annotation of this pathway.", "of this pathway. once", "this pathway. once primed", "pathway. once primed the", "once primed the synaptic", "primed the synaptic vesicle", "the synaptic vesicle is", "synaptic vesicle is ready", "vesicle is ready for", "is ready for release.


synaptic", "ready for release.


synaptic transmission", "for release.


synaptic transmission involves", "release.


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neurotransmitter", "in the neurotransmitter release.", "the neurotransmitter release. ca2+", "neurotransmitter release. ca2+ influx", "release. ca2+ influx through", "ca2+ influx through these", "influx through these channels", "through these channels results", "these channels results in", "channels results in the", "results in the rise", "in the rise of", "the rise of intracellular", "rise of intracellular ca2+", "of intracellular ca2+ concentration.", "intracellular ca2+ concentration. in", "ca2+ concentration. in the", "concentration. in the microdomain", "in the microdomain of", "the microdomain of glutamatergic", "microdomain of glutamatergic synapses", "glutamatergic synapses the", "synapses the ca2+", "the ca2+ concentration could", "ca2+ concentration could rise", "concentration could rise between", "could rise between 10", "rise between 10 25", "between 10 25 micro", "10 25 micro molar.", "micro molar. synaptotagmin", "synaptotagmin a ca2+", "a ca2+ binding protein", "ca2+ binding protein located", "binding protein located in", "protein located in the", "the synaptic vesicular membrane", "vesicular membrane responds", "membrane responds to", "responds to the rise", "to the rise in", "the rise in the", "rise in the ca2+", "in the ca2+ levels", "the ca2+ levels in", "ca2+ levels in the", "levels in the microdomain", "in the microdomain and", "the microdomain and induces", "microdomain and induces a", "and induces a synaptic", "induces a synaptic vesicle", "a synaptic vesicle membrane", "synaptic vesicle membrane curvature", "vesicle membrane curvature that", "membrane curvature that favors", "curvature that favors vesicle", "that favors vesicle fusion.", "favors vesicle fusion. fusion", "vesicle fusion. fusion of", "fusion. fusion of the", "fusion of the synaptic", "of the synaptic vesicle", "the synaptic vesicle with", "synaptic vesicle with the", "vesicle with the plasma", "with the plasma membrane", "the plasma membrane is", "plasma membrane is characterized", "membrane is characterized by", "is characterized by the", "characterized by the formation", "by the formation of", "the formation of a", "formation of a trimeric", "of a trimeric trans", "a trimeric trans snare", "trimeric trans snare complex", "trans snare complex that", "snare complex that involves", "complex that involves vamp2", "that involves vamp2 from", "involves vamp2 from the", "vamp2 from the synaptic", "from the synaptic vesicle", "the synaptic vesicle membrane", "vesicle membrane and", "membrane and syntaxin", "and syntaxin and snap", "syntaxin and snap 25", "and snap 25 from", "snap 25 from plasma", "25 from plasma membrane.", "from plasma membrane. vesicle", "plasma membrane. vesicle fusion", "membrane. vesicle fusion incorporates", "vesicle fusion incorporates the", "fusion incorporates the synaptic", "incorporates the synaptic vesicle", "synaptic vesicle membrane into", "vesicle membrane into the", "membrane into the plasma", "into the plasma membrane", "plasma membrane releasing", "membrane releasing the", "releasing the vesicle contents", "vesicle contents glutamate", "into the synaptic cleft.", "the synaptic cleft. postfusion", "synaptic cleft. postfusion the", "cleft. postfusion the synaptic", "postfusion the synaptic vesicle", "synaptic vesicle membrane proteins", "membrane proteins vamp2", "vglut1 and synaptotagmin", "and synaptotagmin are", "synaptotagmin are also", "are also found in", "also found in the", "found in the plasma", "in the plasma membrane.", "communication at the synapse involves", "at the synapse involves the", "the synapse involves the release", "synapse involves the release of", "involves the release of glutamate", "the release of glutamate from", "release of glutamate from the", "of glutamate from the presynaptic", "glutamate from the presynaptic neuron", "from the presynaptic neuron and", "the presynaptic neuron and its", "presynaptic neuron and its binding", "neuron and its binding to", "and its binding to glutamate", "its binding to glutamate receptors", "binding to glutamate receptors on", "to glutamate receptors on the", "glutamate receptors on the postsynaptic", "receptors on the postsynaptic cell", "on the postsynaptic cell to", "the postsynaptic cell to generate", "postsynaptic cell to generate a", "cell to generate a series", "to generate a series of", "generate a series of events", "a series of events that", "series of events that lead", "of events that lead to", "events that lead to propagation", "that lead to propagation of", "lead to propagation of the", "to propagation of the synaptic", "propagation of the synaptic transmission.", "of the synaptic transmission. this", "the synaptic transmission. this process", "synaptic transmission. this process begins", "transmission. this process begins with", "this process begins with the", "process begins with the formation", "begins with the formation of", "with the formation of synaptic", "the formation of synaptic vesicles", 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the", "into the synaptic cleft.

the glutamate", "the synaptic cleft.

the glutamate life", "synaptic cleft.

the glutamate life cycle", "cleft.

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the", "to the plasma membrane.


the docked", "the plasma membrane.


the docked synaptic", "plasma membrane.


the docked synaptic vesicle", "membrane.


the docked synaptic vesicle is", "docked synaptic vesicle is not", "synaptic vesicle is not ready", "vesicle is not ready for", "is not ready for release", "not ready for release until", "ready for release until it", "for release until it undergoes", "release until it undergoes molecular", "until it undergoes molecular changes", "it undergoes molecular changes to", "undergoes molecular changes to prime", "molecular changes to prime it", "changes to prime it for", "to prime it for fusion", "prime it for fusion with", "it for fusion with the", "for fusion with the plasma", "fusion with the plasma membrane.", "with the plasma membrane. munc13", "the plasma membrane. munc13 is", "plasma membrane. munc13 is one", "membrane. munc13 is one of", "munc13 is one of the", "is one of the main", "one of the main players", "of the main players in", "the main players in the", "main players in the priming", "players in the priming process.", "in the priming process. munc", "the priming process. munc 13", "priming process. munc 13 interacts", "process. munc 13 interacts with", "munc 13 interacts with rim", "interacts with rim rab3a", "with rim rab3a interacting", "rim rab3a interacting molecule", "rab3a interacting molecule located", "interacting molecule located in", "molecule located in the", "located in the synaptic vesicle.", "in the synaptic vesicle. munc", "the synaptic vesicle. munc 13", "synaptic vesicle. munc 13 also", "vesicle. munc 13 also interacts", "munc 13 also interacts with", "13 also interacts with doc2.", "also interacts with doc2. the", "interacts with doc2. the precise", "with doc2. the precise molecular", "doc2. the precise molecular mechanisms", "the precise molecular mechanisms of", "precise molecular mechanisms of the", "molecular mechanisms of the interactions", "mechanisms of the interactions that", "of the interactions that result", "the interactions that result in", "interactions that result in docking", "that result in docking versus", "result in docking versus priming", "in docking versus priming are", "docking versus priming are not", "versus priming are not clear", "priming are not clear and", "are not clear and the", "not clear and the docking", "clear and the docking and", "and the docking and priming", "the docking and priming process", "docking and priming process have", "and priming process have been", "priming process have been combined", "process have been combined in", "have been combined in this", "been combined in this annotation", "combined in this annotation of", "in this annotation of this", "this annotation of this pathway.", "annotation of this pathway. once", "of this pathway. once primed", "this pathway. once primed the", "pathway. once primed the synaptic", "once primed the synaptic vesicle", "primed the synaptic vesicle is", "the synaptic vesicle is ready", "synaptic vesicle is ready for", "vesicle is ready for release.


synaptic", "is ready for release.


synaptic transmission", "ready for release.


synaptic transmission involves", "for release.


synaptic transmission involves an", "release.


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p/q and", "n p/q and r", "p/q and r type of", "and r type of vgccs", "r type of vgccs are", "type of vgccs are involved", "of vgccs are involved in", "vgccs are involved in the", "are involved in the neurotransmitter", "involved in the neurotransmitter release.", "in the neurotransmitter release. ca2+", "the neurotransmitter release. ca2+ influx", "neurotransmitter release. ca2+ influx through", "release. ca2+ influx through these", "ca2+ influx through these channels", "influx through these channels results", "through these channels results in", "these channels results in the", "channels results in the rise", "results in the rise of", "in the rise of intracellular", "the rise of intracellular ca2+", "rise of intracellular ca2+ concentration.", "of intracellular ca2+ concentration. in", "intracellular ca2+ concentration. in the", "ca2+ concentration. in the microdomain", "concentration. in the microdomain of", "in the microdomain of glutamatergic", "the microdomain of glutamatergic synapses", "of glutamatergic synapses the", "glutamatergic synapses the ca2+", "synapses the ca2+ concentration", "the ca2+ concentration could rise", "ca2+ concentration could rise between", "concentration could rise between 10", "could rise between 10 25", "rise between 10 25 micro", "between 10 25 micro molar.", "25 micro molar. synaptotagmin", "molar. synaptotagmin a", "synaptotagmin a ca2+ binding", "a ca2+ binding protein located", "ca2+ binding protein located in", "binding protein located in the", "protein located in the synaptic", "in the synaptic vesicular membrane", "synaptic vesicular membrane responds", "vesicular membrane responds to", "membrane responds to the", "responds to the rise in", "to the rise in the", "the rise in the ca2+", "rise in the ca2+ levels", "in the ca2+ levels in", "the ca2+ levels in the", "ca2+ levels in the microdomain", "levels in the microdomain and", "in the microdomain and induces", "the microdomain and induces a", "microdomain and induces a synaptic", "and induces a synaptic vesicle", "induces a synaptic vesicle membrane", "a synaptic vesicle membrane curvature", "synaptic vesicle membrane curvature that", "vesicle membrane curvature that favors", "membrane curvature that favors vesicle", "curvature that favors vesicle fusion.", "that favors vesicle fusion. fusion", "favors vesicle fusion. fusion of", "vesicle fusion. fusion of the", "fusion. fusion of the synaptic", "fusion of the synaptic vesicle", "of the synaptic vesicle with", "the synaptic vesicle with the", "synaptic vesicle with the plasma", "vesicle with the plasma membrane", "with the plasma membrane is", "the plasma membrane is characterized", "plasma membrane is characterized by", "membrane is characterized by the", "is characterized by the formation", "characterized by the formation of", "by the formation of a", "the formation of a trimeric", "formation of a trimeric trans", "of a trimeric trans snare", "a trimeric trans snare complex", "trimeric trans snare complex that", "trans snare complex that involves", "snare complex that involves vamp2", "complex that involves vamp2 from", "that involves vamp2 from the", "involves vamp2 from the synaptic", "vamp2 from the synaptic vesicle", "from the synaptic vesicle membrane", "synaptic vesicle membrane and", "vesicle membrane and syntaxin", "membrane and syntaxin and", "and syntaxin and snap 25", "syntaxin and snap 25 from", "and snap 25 from plasma", "snap 25 from plasma membrane.", "25 from plasma membrane. vesicle", "from plasma membrane. vesicle fusion", "plasma membrane. vesicle fusion incorporates", "membrane. vesicle fusion incorporates the", "vesicle fusion incorporates the synaptic", "fusion incorporates the synaptic vesicle", "incorporates the synaptic vesicle membrane", "the synaptic vesicle membrane into", "synaptic vesicle membrane into the", "vesicle membrane into the plasma", "membrane into the plasma membrane", "the plasma membrane releasing", "plasma membrane releasing the", "membrane releasing the vesicle", "the vesicle contents glutamate", "contents glutamate into", "into the synaptic cleft. postfusion", "the synaptic cleft. postfusion the", "synaptic cleft. postfusion the synaptic", "cleft. postfusion the synaptic vesicle", "postfusion the synaptic vesicle membrane", "the synaptic vesicle membrane proteins", "vesicle membrane proteins vamp2", "proteins vamp2 rab3a", "vamp2 rab3a vglut1", "rab3a vglut1 and", "and synaptotagmin are also", "synaptotagmin are also found", "are also found in the", "also found in the plasma", "found in the plasma membrane." ] }, { "record_id": "GLY_000594_1_203", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "210991", "r hsa", "hsa 210991", "r hsa 210991" ] }, { "record_id": "GLY_000594_1_203", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "basigin interactions", "basigin is", "is a", "a widely", "widely expressed", "expressed 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these ligands", "undergoes activation.
these ligands show", "activation.
these ligands show opposing", "ligands show opposing actions", "opposing actions angiopoietin", "actions angiopoietin 1", "angiopoietin 1 and angiopoietin", "1 and angiopoietin 4", "and angiopoietin 4 stimulate", "angiopoietin 4 stimulate the", "4 stimulate the tie2", "stimulate the tie2 phosphorylation", "the tie2 phosphorylation and", "tie2 phosphorylation and angiopoietin", "phosphorylation and angiopoietin 2", "and angiopoietin 2 inhibits", "angiopoietin 2 inhibits it.", "2 inhibits it. upon", "inhibits it. upon tyrosine", "it. upon tyrosine phosphorylation", "upon tyrosine phosphorylation tie2", "tyrosine phosphorylation tie2 acts", "phosphorylation tie2 acts as", "tie2 acts as a", "acts as a scaffold", "as a scaffold for", "a scaffold for various", "scaffold for various signaling", "for various signaling proteins", "various signaling proteins involved", "signaling proteins involved in", "proteins involved in different", "involved in different signal", "in different signal transduction", "different signal transduction cascades", "signal transduction cascades that", "transduction cascades that can", "cascades that can effect", "that can effect survival", "can effect survival of", "effect survival of endothelium", "survival of endothelium and", "of endothelium and angiogenic", "endothelium and angiogenic sprout", "and angiogenic sprout formation.", "the tie2/tek receptor tyrosine kinase", "tie2/tek receptor tyrosine kinase plays", "receptor tyrosine kinase plays a", "tyrosine kinase plays a pivotal", "kinase plays a pivotal role", "plays a pivotal role in", "a pivotal role in vascular", "pivotal role in vascular and", "role in vascular and hematopoietic", "in vascular and hematopoietic development", "vascular and hematopoietic development and", "and hematopoietic development and is", "hematopoietic development and is expressed", "development and is expressed exclusively", "and is expressed exclusively on", "is expressed exclusively on endothelial", "expressed exclusively on endothelial lineage.", "exclusively on endothelial lineage. tie2", "on endothelial lineage. tie2 interacts", "endothelial lineage. tie2 interacts with", "lineage. tie2 interacts with a", "tie2 interacts with a group", "interacts with a group of", "with a group of ligands", "a group of ligands belonging", "group of ligands belonging to", "of ligands belonging to angiopoietin", "ligands belonging to angiopoietin family", "belonging to angiopoietin family and", "to angiopoietin family and undergoes", "angiopoietin family and undergoes activation.
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intracellular domain regulates transcription", "nicd1 produced", "produced by", "by activation", "activation of", "of notch1", "notch1 in", "in response", "response to", "to delta", "delta and", "and jagged", "jagged ligands", "presented in", "in trans", "traffics to", "to the", "the nucleus", "nucleus where", "where it", "it acts", "acts as", "as a", "a transcription", "transcription regulator.", "regulator. in", "in the", "nicd1 displaces", "displaces the", "the ncor", "ncor corepressor", "corepressor complex", "complex from", "from rbpj", "csl .", ". when", "when bound", "bound to", "the co", "co repressor", "repressor complex", "complex that", "that includes", "includes ncor", "ncor proteins", "ncor1 and", "and ncor2", "and hdac", "hdac histone", "histone deacetylases", "represses transcription", "transcription of", "of notch", "notch target", "target genes", "kao et", "et al.", "al. 1998", "zhou et", "al. 2000", "perissi et", "al. 2004", "al. 2008", "2008 .", ". once", "once the", "complex is", "is displaced", "nicd1 recruits", "recruits maml", "mastermind like", "to rbpj", "while maml", "maml recruits", "recruits histone", "histone acetyltransferases", "acetyltransferases ep300", "and pcaf", "resulting in", "in formation", "formation of", "of the", "the notch", "notch coactivator", "coactivator complex", "that activates", "activates transcription", "transcription from", "from notch", "notch regulatory", "regulatory elements.", "elements. the", "the minimal", "minimal functional", "functional notch", "regulatory elements", "elements is", "is a", "a heterotrimer", "heterotrimer composed", "composed of", "of nicd", "maml and", "and rbpj", "fryer et", "al. 2002", "wallberg et", "nam et", "al. 2006", "2006 .", ".

", "


notch1", "
notch1 coactivator", "is known", "known to", "to activate", "activate transcription", "of hes1", "jarriault et", "al. 1995", "arnett et", "al. 2010", "hey genes", "fischer et", "leimeister et", "maier et", "and myc", "palomero et", "and likely", "likely regulates", "of many", "many other", "other genes", "wang et", "al. 2011", "2011 .", ". notch1", "notch1 coactivator", "complex on", "on any", "any specific", "specific regulatory", "regulatory element", "element may", "may involve", "involve additional", "additional transcriptional", "transcriptional regulatory", "regulatory proteins.", "proteins. hes1", "hes1 binds", "binds tle", "tle proteins", "forming an", "an evolutionarily", "evolutionarily conserved", "conserved transcriptional", "transcriptional corepressor", "corepressor involved", "involved in", "in regulation", "regulation of", "of neurogenesis", "segmentation and", "and sex", "sex determination", "grbavec et", "al. 1996", "fisher et", "paroush et", "al. 1994", "1994 .", ".

after", "

after notch1", "is assembled", "assembled on", "on a", "a notch", "notch responsive", "responsive promoter", "recruits cdk8", "cdk8 in", "in complex", "complex with", "with cyclin", "cyclin c", "triggering phosphorylation", "phosphorylation of", "of conserved", "conserved serine", "serine residues", "residues in", "in tad", "tad and", "and pest", "pest domains", "domains of", "of nicd1", "nicd1 by", "by cdk8.", "cdk8. phosphorylated", "phosphorylated nicd1", "nicd1 is", "is recognized", "recognized by", "by the", "the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase fbxw7", "fbxw7 which", "which ubiquitinates", "ubiquitinates nicd1", "leading to", "to degradation", "degradation of", "nicd1 and", "and downregulation", "downregulation of", "notch1 signaling.", "signaling. fbxw7", "fbxw7 mediated", "mediated ubiquitination", "ubiquitination and", "and degradation", "notch1 depend", "depend on", "on c", "c terminally", "terminally located", "located pest", "pest domain", "domain sequences", "sequences in", "in notch1", "oberg et", "al. 2001", "wu et", "2001 .", ". the", "the pest", "domain of", "notch1 and", "and the", "the substrate", "substrate binding", "binding wd40", "wd40 domain", "of fbxw7", "fbxw7 are", "are frequent", "frequent targets", "targets of", "of mutations", "mutations in", "in t", "t cell", "cell acute", "acute lymphoblastic", "lymphoblastic leukemia", "t all", "welcker and", "and clurman", "clurman 2008", "

nicd1", "which normally", "normally has", "has a", "a short", "short half", "half life", "can be", "be stabilized", "stabilized by", "by binding", "binding to", "the hypoxia", "hypoxia inducable", "inducable factor", "factor 1", "1 alpha", "which accumulates", "accumulates in", "nucleus when", "when oxygen", "oxygen levels", "levels are", "are low.", "low. this", "this results", "results in", "in hif1a", "hif1a induced", "induced inhibition", "inhibition of", "of cellular", "cellular differentiation", "differentiation that", "that is", "is notch", "notch dependent", "gustafsson et", "al. 2005", "2005 .", "nicd1 produced by", "produced by activation", "by activation of", "activation of notch1", "of notch1 in", "notch1 in response", "in response to", "response to delta", "to delta and", "delta and jagged", "and jagged ligands", "ligands dll/jag", "dll/jag presented", "presented in trans", "trans traffics", "traffics to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it acts", "it acts as", "acts as a", "as a transcription", "a transcription regulator.", "transcription regulator. in", "regulator. in the", "in the nucleus", "nucleus nicd1", "nicd1 displaces the", "displaces the ncor", "the ncor corepressor", "ncor corepressor complex", "corepressor complex from", "complex from rbpj", "rbpj csl", "csl . when", ". when bound", "when bound to", "bound to the", "to the co", "the co repressor", "co repressor complex", "repressor complex that", "complex that includes", "that includes ncor", "includes ncor proteins", "proteins ncor1", "ncor1 and ncor2", "ncor2 and", "and hdac histone", "hdac histone deacetylases", "deacetylases rbpj", "csl represses", "represses transcription of", "transcription of notch", "of notch target", "notch target genes", "genes kao", "kao et al.", "et al. 1998", "1998 zhou", "zhou et al.", "et al. 2000", "2000 perissi", "perissi et al.", "et al. 2004", "2004 perissi", "et al. 2008", "al. 2008 .", "2008 . once", ". once the", "once the co", "repressor complex is", "complex is displaced", "displaced nicd1", "nicd1 recruits maml", "maml mastermind", "like to", "rbpj while", "while maml recruits", "maml recruits histone", "recruits histone acetyltransferases", "histone acetyltransferases ep300", "ep300 p300", "p300 and", "pcaf resulting", "resulting in formation", "in formation of", "formation of the", "of the notch", "the notch coactivator", "notch coactivator complex", "coactivator complex that", "complex that activates", "that activates transcription", "activates transcription from", "transcription from notch", "from notch regulatory", "notch regulatory elements.", "regulatory elements. the", "elements. the minimal", "the minimal functional", "minimal functional notch", "functional notch coactivator", "notch regulatory elements", "regulatory elements is", "elements is a", "is a heterotrimer", "a heterotrimer composed", "heterotrimer composed of", "composed of nicd", "nicd maml", "maml and rbpj", "rbpj fryer", "fryer et al.", "et al. 2002", "2002 wallberg", "wallberg et al.", "2002 nam", "nam et al.", "et al. 2006", "al. 2006 .", "2006 .

", ".


notch1", "


notch1 coactivator", "
notch1 coactivator complex", "coactivator complex is", "complex is known", "is known to", "known to activate", "to activate transcription", "activate transcription of", "transcription of hes1", "hes1 jarriault", "jarriault et al.", "et al. 1995", "hes5 arnett", "arnett et al.", "et al. 2010", "genes fischer", "fischer et al.", "2004 leimeister", "leimeister et al.", "2000 maier", "maier et al.", "2000 arnett", "2010 and", "myc palomero", "palomero et al.", "2006 and", "and likely regulates", "likely regulates transcription", "regulates transcription of", "transcription of many", "of many other", "many other genes", "genes wang", "wang et al.", "et al. 2011", "al. 2011 .", "2011 . notch1", ". notch1 coactivator", "notch1 coactivator complex", "coactivator complex on", "complex on any", "on any specific", "any specific regulatory", "specific regulatory element", "regulatory element may", "element may involve", "may involve additional", "involve additional transcriptional", "additional transcriptional regulatory", "transcriptional regulatory proteins.", "regulatory proteins. hes1", "proteins. hes1 binds", "hes1 binds tle", "binds tle proteins", "proteins forming", "forming an evolutionarily", "an evolutionarily conserved", "evolutionarily conserved transcriptional", "conserved transcriptional corepressor", "transcriptional corepressor involved", "corepressor involved in", "involved in regulation", "in regulation of", "regulation of neurogenesis", "neurogenesis segmentation", "segmentation and sex", "and sex determination", "determination grbavec", "grbavec et al.", "et al. 1996", "1996 fisher", "fisher et al.", "1996 paroush", "paroush et al.", "et al. 1994", "al. 1994 .", "1994 .

after", ".

after notch1", "

after notch1 coactivator", "complex is assembled", "is assembled on", "assembled on a", "on a notch", "a notch responsive", "notch responsive promoter", "promoter maml", "like recruits", "recruits cdk8 in", "cdk8 in complex", "in complex with", "complex with cyclin", "with cyclin c", "c triggering", "triggering phosphorylation of", "phosphorylation of conserved", "of conserved serine", "conserved serine residues", "serine residues in", "residues in tad", "in tad and", "tad and pest", "and pest domains", "pest domains of", "domains of nicd1", "of nicd1 by", "nicd1 by cdk8.", "by cdk8. phosphorylated", "cdk8. phosphorylated nicd1", "phosphorylated nicd1 is", "nicd1 is recognized", "is recognized by", "recognized by the", "by the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase fbxw7", "ligase fbxw7 which", "fbxw7 which ubiquitinates", "which ubiquitinates nicd1", "nicd1 leading", "leading to degradation", "to degradation of", "degradation of nicd1", "of nicd1 and", "nicd1 and downregulation", "and downregulation of", "downregulation of notch1", "of notch1 signaling.", "notch1 signaling. fbxw7", "signaling. fbxw7 mediated", "fbxw7 mediated ubiquitination", "mediated ubiquitination and", "ubiquitination and degradation", "and degradation of", "degradation of notch1", "of notch1 depend", "notch1 depend on", "depend on c", "on c terminally", "c terminally located", "terminally located pest", "located pest domain", "pest domain sequences", "domain sequences in", "sequences in notch1", "notch1 fryer", "2004 oberg", "oberg et al.", "et al. 2001", "2001 wu", "wu et al.", "al. 2001 .", "2001 . the", ". the pest", "the pest domain", "pest domain of", "domain of notch1", "of notch1 and", "notch1 and the", "and the substrate", "the substrate binding", "substrate binding wd40", "binding wd40 domain", "wd40 domain of", "domain of fbxw7", "of fbxw7 are", "fbxw7 are frequent", "are frequent targets", "frequent targets of", "targets of mutations", "of mutations in", "mutations in t", "in t cell", "t cell acute", "cell acute lymphoblastic", "acute lymphoblastic leukemia", "all welcker", "welcker and clurman", "and clurman 2008", "clurman 2008 .", "2008 .

", ".

nicd1", "nicd1 which", "which normally has", "normally has a", "has a short", "a short half", "short half life", "life can", "can be stabilized", "be stabilized by", "stabilized by binding", "by binding to", "binding to the", "to the hypoxia", "the hypoxia inducable", "hypoxia inducable factor", "inducable factor 1", "factor 1 alpha", "alpha hif1a", "hif1a which", "which accumulates in", "accumulates in the", "the nucleus when", "nucleus when oxygen", "when oxygen levels", "oxygen levels are", "levels are low.", "are low. this", "low. this results", "this results in", "results in hif1a", "in hif1a induced", "hif1a induced inhibition", "induced inhibition of", "inhibition of cellular", "of cellular differentiation", "cellular differentiation that", "differentiation that is", "that is notch", "is notch dependent", "dependent gustafsson", "gustafsson et al.", "et al. 2005", "al. 2005 .", "nicd1 produced by activation", "produced by activation of", "by activation of notch1", "activation of notch1 in", "of notch1 in response", "notch1 in response to", "in response to delta", "response to delta and", "to delta and jagged", "delta and jagged ligands", "jagged ligands dll/jag", "dll/jag presented in", "in trans traffics", "trans traffics to", "traffics to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it acts", "where it acts as", "it acts as a", "acts as a transcription", "as a transcription regulator.", "a transcription regulator. in", "transcription regulator. in the", "regulator. in the nucleus", "the nucleus nicd1", "nucleus nicd1 displaces", "nicd1 displaces the ncor", "displaces the ncor corepressor", "the ncor corepressor complex", "ncor corepressor complex from", "corepressor complex from rbpj", "from rbpj csl", "rbpj csl .", "csl . when bound", ". when bound to", "when bound to the", "bound to the co", "to the co repressor", "the co repressor complex", "co repressor complex that", "repressor complex that includes", "complex that includes ncor", "that includes ncor proteins", "ncor proteins ncor1", "proteins ncor1 and", "and ncor2 and", "ncor2 and hdac", "and hdac histone deacetylases", "histone deacetylases rbpj", "csl represses transcription", "represses transcription of notch", "transcription of notch target", "of notch target genes", "target genes kao", "genes kao et", "kao et al. 1998", "al. 1998 zhou", "1998 zhou et", "zhou et al. 2000", "al. 2000 perissi", "2000 perissi et", "perissi et al. 2004", "al. 2004 perissi", "2004 perissi et", "perissi et al. 2008", "et al. 2008 .", "al. 2008 . once", "2008 . once the", ". once the co", "once the co repressor", "co repressor complex is", "repressor complex is displaced", "is displaced nicd1", "displaced nicd1 recruits", "recruits maml mastermind", "maml mastermind like", "mastermind like to", "like to rbpj", "to rbpj while", "rbpj while maml", "while maml recruits histone", "maml recruits histone acetyltransferases", "recruits histone acetyltransferases ep300", "acetyltransferases ep300 p300", "p300 and pcaf", "and pcaf resulting", "pcaf resulting in", "resulting in formation of", "in formation of the", "formation of the notch", "of the notch coactivator", "the notch coactivator complex", "notch coactivator complex that", "coactivator complex that activates", "complex that activates transcription", "that activates transcription from", "activates transcription from notch", "transcription from notch regulatory", "from notch regulatory elements.", "notch regulatory elements. the", "regulatory elements. the minimal", "elements. the minimal functional", "the minimal functional notch", "minimal functional notch coactivator", "functional notch coactivator complex", "from notch regulatory elements", "notch regulatory elements is", "regulatory elements is a", "elements is a heterotrimer", "is a heterotrimer composed", "a heterotrimer composed of", "heterotrimer composed of nicd", "of nicd maml", "nicd maml and", "and rbpj fryer", "rbpj fryer et", "fryer et al. 2002", "al. 2002 wallberg", "2002 wallberg et", "wallberg et al. 2002", "al. 2002 nam", "2002 nam et", "nam et al. 2006", "et al. 2006 .", "al. 2006 .

", "2006 .


notch1", ".


notch1 coactivator", "


notch1 coactivator complex", "
notch1 coactivator complex is", "coactivator complex is known", "complex is known to", "is known to activate", "known to activate transcription", "to activate transcription of", "activate transcription of hes1", "of hes1 jarriault", "hes1 jarriault et", "jarriault et al. 1995", "1995 hes5", "hes5 arnett et", "arnett et al. 2010", "2010 hey", "hey genes fischer", "genes fischer et", "fischer et al. 2004", "al. 2004 leimeister", "2004 leimeister et", "leimeister et al. 2000", "al. 2000 maier", "2000 maier et", "maier et al. 2000", "al. 2000 arnett", "2000 arnett et", "al. 2010 and", "2010 and myc", "and myc palomero", "myc palomero et", "palomero et al. 2006", "al. 2006 and", "2006 and likely", "and likely regulates transcription", "likely regulates transcription of", "regulates transcription of many", "transcription of many other", "of many other genes", "other genes wang", "genes wang et", "wang et al. 2011", "et al. 2011 .", "al. 2011 . notch1", "2011 . notch1 coactivator", ". notch1 coactivator complex", "notch1 coactivator complex on", "coactivator complex on any", "complex on any specific", "on any specific regulatory", "any specific regulatory element", "specific regulatory element may", "regulatory element may involve", "element may involve additional", "may involve additional transcriptional", "involve additional transcriptional regulatory", "additional transcriptional regulatory proteins.", "transcriptional regulatory proteins. hes1", "regulatory proteins. hes1 binds", "proteins. hes1 binds tle", "hes1 binds tle proteins", "tle proteins forming", "proteins forming an", "forming an evolutionarily conserved", "an evolutionarily conserved transcriptional", "evolutionarily conserved transcriptional corepressor", "conserved transcriptional corepressor involved", "transcriptional corepressor involved in", "corepressor involved in regulation", "involved in regulation of", "in regulation of neurogenesis", "of neurogenesis segmentation", "neurogenesis segmentation and", "segmentation and sex determination", "sex determination grbavec", "determination grbavec et", "grbavec et al. 1996", "al. 1996 fisher", "1996 fisher et", "fisher et al. 1996", "al. 1996 paroush", "1996 paroush et", "paroush et al. 1994", "et al. 1994 .", "al. 1994 .

after", "1994 .

after notch1", ".

after notch1 coactivator", "

after notch1 coactivator complex", "notch1 coactivator complex is", "coactivator complex is assembled", "complex is assembled on", "is assembled on a", "assembled on a notch", "on a notch responsive", "a notch responsive promoter", "responsive promoter maml", "mastermind like recruits", "like recruits cdk8", "recruits cdk8 in complex", "cdk8 in complex with", "in complex with cyclin", "complex with cyclin c", "cyclin c triggering", "c triggering phosphorylation", "triggering phosphorylation of conserved", "phosphorylation of conserved serine", "of conserved serine residues", "conserved serine residues in", "serine residues in tad", "residues in tad and", "in tad and pest", "tad and pest domains", "and pest domains of", "pest domains of nicd1", "domains of nicd1 by", "of nicd1 by cdk8.", "nicd1 by cdk8. phosphorylated", "by cdk8. phosphorylated nicd1", "cdk8. phosphorylated nicd1 is", "phosphorylated nicd1 is recognized", "nicd1 is recognized by", "is recognized by the", "recognized by the e3", "by the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase fbxw7", "ubiquitin ligase fbxw7 which", "ligase fbxw7 which ubiquitinates", "fbxw7 which ubiquitinates nicd1", "ubiquitinates nicd1 leading", "nicd1 leading to", "leading to degradation of", "to degradation of nicd1", "degradation of nicd1 and", "of nicd1 and downregulation", "nicd1 and downregulation of", "and downregulation of notch1", "downregulation of notch1 signaling.", "of notch1 signaling. fbxw7", "notch1 signaling. fbxw7 mediated", "signaling. fbxw7 mediated ubiquitination", "fbxw7 mediated ubiquitination and", "mediated ubiquitination and degradation", "ubiquitination and degradation of", "and degradation of notch1", "degradation of notch1 depend", "of notch1 depend on", "notch1 depend on c", "depend on c terminally", "on c terminally located", "c terminally located pest", "terminally located pest domain", "located pest domain sequences", "pest domain sequences in", "domain sequences in notch1", "in notch1 fryer", "notch1 fryer et", "fryer et al. 2004", "al. 2004 oberg", "2004 oberg et", "oberg et al. 2001", "al. 2001 wu", "2001 wu et", "wu et al. 2001", "et al. 2001 .", "al. 2001 . the", "2001 . the pest", ". the pest domain", "the pest domain of", "pest domain of notch1", "domain of notch1 and", "of notch1 and the", "notch1 and the substrate", "and the substrate binding", "the substrate binding wd40", "substrate binding wd40 domain", "binding wd40 domain of", "wd40 domain of fbxw7", "domain of fbxw7 are", "of fbxw7 are frequent", "fbxw7 are frequent targets", "are frequent targets of", "frequent targets of mutations", "targets of mutations in", "of mutations in t", "mutations in t cell", "in t cell acute", "t cell acute lymphoblastic", "cell acute lymphoblastic leukemia", "leukemia t", "t all welcker", "all welcker and", "welcker and clurman 2008", "and clurman 2008 .", "clurman 2008 .

", "2008 .

nicd1", "

nicd1 which", "nicd1 which normally", "which normally has a", "normally has a short", "has a short half", "a short half life", "half life can", "life can be", "can be stabilized by", "be stabilized by binding", "stabilized by binding to", "by binding to the", "binding to the hypoxia", "to the hypoxia inducable", "the hypoxia inducable factor", "hypoxia inducable factor 1", "inducable factor 1 alpha", "1 alpha hif1a", "hif1a which accumulates", "which accumulates in the", "accumulates in the nucleus", "in the nucleus when", "the nucleus when oxygen", "nucleus when oxygen levels", "when oxygen levels are", "oxygen levels are low.", "levels are low. this", "are low. this results", "low. this results in", "this results in hif1a", "results in hif1a induced", "in hif1a induced inhibition", "hif1a induced inhibition of", "induced inhibition of cellular", "inhibition of cellular differentiation", "of cellular differentiation that", "cellular differentiation that is", "differentiation that is notch", "that is notch dependent", "notch dependent gustafsson", "dependent gustafsson et", "gustafsson et al. 2005", "et al. 2005 .", "nicd1 produced by activation of", "produced by activation of notch1", "by activation of notch1 in", "activation of notch1 in response", "of notch1 in response to", "notch1 in response to delta", "in response to delta and", "response to delta and jagged", "to delta and jagged ligands", "and jagged ligands dll/jag", "ligands dll/jag presented", "dll/jag presented in trans", "presented in trans traffics", "in trans traffics to", "trans traffics to the", "traffics to the nucleus where", "to the nucleus where it", "the nucleus where it acts", "nucleus where it acts as", "where it acts as a", "it acts as a transcription", "acts as a transcription regulator.", "as a transcription regulator. in", "a transcription regulator. in the", "transcription regulator. in the nucleus", "in the nucleus nicd1", "the nucleus nicd1 displaces", "nucleus nicd1 displaces the", "nicd1 displaces the ncor corepressor", "displaces the ncor corepressor complex", "the ncor corepressor complex from", "ncor corepressor complex from rbpj", "complex from rbpj csl", "from rbpj csl .", "rbpj csl . when", "csl . when bound to", ". when bound to the", "when bound to the co", "bound to the co repressor", "to the co repressor complex", "the co repressor complex that", "co repressor complex that includes", "repressor complex that includes ncor", "complex that includes ncor proteins", "includes ncor proteins ncor1", "ncor proteins ncor1 and", "proteins ncor1 and ncor2", "ncor1 and ncor2 and", "and ncor2 and hdac", "ncor2 and hdac histone", "hdac histone deacetylases rbpj", "deacetylases rbpj csl", "rbpj csl represses", "csl represses transcription of", "represses transcription of notch target", "transcription of notch target genes", "notch target genes kao", "target genes kao et", "genes kao et al.", "et al. 1998 zhou", "al. 1998 zhou et", "1998 zhou et al.", "et al. 2000 perissi", "al. 2000 perissi et", "2000 perissi et al.", "et al. 2004 perissi", "al. 2004 perissi et", "2004 perissi et al.", "perissi et al. 2008 .", "et al. 2008 . once", "al. 2008 . once the", "2008 . once the co", ". once the co repressor", "once the co repressor complex", "the co repressor complex is", "co repressor complex is displaced", "complex is displaced nicd1", "is displaced nicd1 recruits", "displaced nicd1 recruits maml", "nicd1 recruits maml mastermind", "recruits maml mastermind like", "mastermind like to rbpj", "to rbpj while maml", "rbpj while maml recruits", "while maml recruits histone acetyltransferases", "maml recruits histone acetyltransferases ep300", "histone acetyltransferases ep300 p300", "ep300 p300 and", "and pcaf resulting in", "pcaf resulting in formation", "resulting in formation of the", "in formation of the notch", "formation of the notch coactivator", "of the notch coactivator complex", "the notch coactivator complex that", "notch coactivator complex that activates", "coactivator complex that activates transcription", "complex that activates transcription from", "that activates transcription from notch", "activates transcription from notch regulatory", "transcription from notch regulatory elements.", "from notch regulatory elements. the", "notch regulatory elements. the minimal", "regulatory elements. the minimal functional", "elements. the minimal functional notch", "the minimal functional notch coactivator", "minimal functional notch coactivator complex", "functional notch coactivator complex that", "transcription from notch regulatory elements", "from notch regulatory elements is", "notch regulatory elements is a", "regulatory elements is a heterotrimer", "elements is a heterotrimer composed", "is a heterotrimer composed of", "a heterotrimer composed of nicd", "composed of nicd maml", "of nicd maml and", "nicd maml and rbpj", "maml and rbpj fryer", "and rbpj fryer et", "rbpj fryer et al.", "et al. 2002 wallberg", "al. 2002 wallberg et", "2002 wallberg et al.", "et al. 2002 nam", "al. 2002 nam et", "2002 nam et al.", "nam et al. 2006 .", "et al. 2006 .

", "al. 2006 .


notch1", "2006 .


notch1 coactivator", ".


notch1 coactivator complex", "


notch1 coactivator complex is", "
notch1 coactivator complex is known", "coactivator complex is known to", "complex is known to activate", "is known to activate transcription", "known to activate transcription of", "to activate transcription of hes1", "transcription of hes1 jarriault", "of hes1 jarriault et", "hes1 jarriault et al.", "al. 1995 hes5", "hes5 arnett et al.", "al. 2010 hey", "2010 hey genes", "hey genes fischer et", "genes fischer et al.", "et al. 2004 leimeister", "al. 2004 leimeister et", "2004 leimeister et al.", "et al. 2000 maier", "al. 2000 maier et", "2000 maier et al.", "et al. 2000 arnett", "al. 2000 arnett et", "2000 arnett et al.", "et al. 2010 and", "al. 2010 and myc", "and myc palomero et", "myc palomero et al.", "et al. 2006 and", "al. 2006 and likely", "2006 and likely regulates", "and likely regulates transcription of", "likely regulates transcription of many", "regulates transcription of many other", "transcription of many other genes", "many other genes wang", "other genes wang et", "genes wang et al.", "wang et al. 2011 .", "et al. 2011 . notch1", "al. 2011 . notch1 coactivator", "2011 . notch1 coactivator complex", ". notch1 coactivator complex on", "notch1 coactivator complex on any", "coactivator complex on any specific", "complex on any specific regulatory", "on any specific regulatory element", "any specific regulatory element may", "specific regulatory element may involve", "regulatory element may involve additional", "element may involve additional transcriptional", "may involve additional transcriptional regulatory", "involve additional transcriptional regulatory proteins.", "additional transcriptional regulatory proteins. hes1", "transcriptional regulatory proteins. hes1 binds", "regulatory proteins. hes1 binds tle", "proteins. hes1 binds tle proteins", "binds tle proteins forming", "tle proteins forming an", "proteins forming an evolutionarily", "forming an evolutionarily conserved transcriptional", "an evolutionarily conserved transcriptional corepressor", "evolutionarily conserved transcriptional corepressor involved", "conserved transcriptional corepressor involved in", "transcriptional corepressor involved in regulation", "corepressor involved in regulation of", "involved in regulation of neurogenesis", "regulation of neurogenesis segmentation", "of neurogenesis segmentation and", "neurogenesis segmentation and sex", "and sex determination grbavec", "sex determination grbavec et", "determination grbavec et al.", "et al. 1996 fisher", "al. 1996 fisher et", "1996 fisher et al.", "et al. 1996 paroush", "al. 1996 paroush et", "1996 paroush et al.", "paroush et al. 1994 .", "et al. 1994 .

after", "al. 1994 .

after notch1", "1994 .

after notch1 coactivator", ".

after notch1 coactivator complex", "

after notch1 coactivator complex is", "notch1 coactivator complex is assembled", "coactivator complex is assembled on", "complex is assembled on a", "is assembled on a notch", "assembled on a notch responsive", "on a notch responsive promoter", "notch responsive promoter maml", "promoter maml mastermind", "mastermind like recruits cdk8", "like recruits cdk8 in", "recruits cdk8 in complex with", "cdk8 in complex with cyclin", "in complex with cyclin c", "with cyclin c triggering", "cyclin c triggering phosphorylation", "c triggering phosphorylation of", "triggering phosphorylation of conserved serine", "phosphorylation of conserved serine residues", "of conserved serine residues in", "conserved serine residues in tad", "serine residues in tad and", "residues in tad and pest", "in tad and pest domains", "tad and pest domains of", "and pest domains of nicd1", "pest domains of nicd1 by", "domains of nicd1 by cdk8.", "of nicd1 by cdk8. phosphorylated", "nicd1 by cdk8. phosphorylated nicd1", "by cdk8. phosphorylated nicd1 is", "cdk8. phosphorylated nicd1 is recognized", "phosphorylated nicd1 is recognized by", "nicd1 is recognized by the", "is recognized by the e3", "recognized by the e3 ubiquitin", "by the e3 ubiquitin ligase", "the e3 ubiquitin ligase fbxw7", "e3 ubiquitin ligase fbxw7 which", "ubiquitin ligase fbxw7 which ubiquitinates", "ligase fbxw7 which ubiquitinates nicd1", "which ubiquitinates nicd1 leading", "ubiquitinates nicd1 leading to", "nicd1 leading to degradation", "leading to degradation of nicd1", "to degradation of nicd1 and", "degradation of nicd1 and downregulation", "of nicd1 and downregulation of", "nicd1 and downregulation of notch1", "and downregulation of notch1 signaling.", "downregulation of notch1 signaling. fbxw7", "of notch1 signaling. fbxw7 mediated", "notch1 signaling. fbxw7 mediated ubiquitination", "signaling. fbxw7 mediated ubiquitination and", "fbxw7 mediated ubiquitination and degradation", "mediated ubiquitination and degradation of", "ubiquitination and degradation of notch1", "and degradation of notch1 depend", "degradation of notch1 depend on", "of notch1 depend on c", "notch1 depend on c terminally", "depend on c terminally located", "on c terminally located pest", "c terminally located pest domain", "terminally located pest domain sequences", "located pest domain sequences in", "pest domain sequences in notch1", "sequences in notch1 fryer", "in notch1 fryer et", "notch1 fryer et al.", "et al. 2004 oberg", "al. 2004 oberg et", "2004 oberg et al.", "et al. 2001 wu", "al. 2001 wu et", "2001 wu et al.", "wu et al. 2001 .", "et al. 2001 . the", "al. 2001 . the pest", "2001 . the pest domain", ". the pest domain of", "the pest domain of notch1", "pest domain of notch1 and", "domain of notch1 and the", "of notch1 and the substrate", "notch1 and the substrate binding", "and the substrate binding wd40", "the substrate binding wd40 domain", "substrate binding wd40 domain of", "binding wd40 domain of fbxw7", "wd40 domain of fbxw7 are", "domain of fbxw7 are frequent", "of fbxw7 are frequent targets", "fbxw7 are frequent targets of", "are frequent targets of mutations", "frequent targets of mutations in", "targets of mutations in t", "of mutations in t cell", "mutations in t cell acute", "in t cell acute lymphoblastic", "t cell acute lymphoblastic leukemia", "lymphoblastic leukemia t", "leukemia t all", "t all welcker and", "all welcker and clurman", "welcker and clurman 2008 .", "and clurman 2008 .

", "clurman 2008 .

nicd1", ".

nicd1 which", "

nicd1 which normally", "nicd1 which normally has", "which normally has a short", "normally has a short half", "has a short half life", "short half life can", "half life can be", "life can be stabilized", "can be stabilized by binding", "be stabilized by binding to", "stabilized by binding to the", "by binding to the hypoxia", "binding to the hypoxia inducable", "to the hypoxia inducable factor", "the hypoxia inducable factor 1", "hypoxia inducable factor 1 alpha", "factor 1 alpha hif1a", "alpha hif1a which", "hif1a which accumulates in", "which accumulates in the nucleus", "accumulates in the nucleus when", "in the nucleus when oxygen", "the nucleus when oxygen levels", "nucleus when oxygen levels are", "when oxygen levels are low.", "oxygen levels are low. this", "levels are low. this results", "are low. this results in", "low. this results in hif1a", "this results in hif1a induced", "results in hif1a induced inhibition", "in hif1a induced inhibition of", "hif1a induced inhibition of cellular", "induced inhibition of cellular differentiation", "inhibition of cellular differentiation that", "of cellular differentiation that is", "cellular differentiation that is notch", "differentiation that is notch dependent", "is notch dependent gustafsson", "notch dependent gustafsson et", "dependent gustafsson et al.", "gustafsson et al. 2005 ." ] }, { "record_id": "GLY_000594_1_211", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2122948", "r hsa", "hsa 2122948", "r hsa 2122948" ] }, { "record_id": "GLY_000594_1_211", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated notch1", "notch1 transmits", "transmits signal", "signal to", "to the", "the nucleus", "activated notch1 transmits", "notch1 transmits signal", "transmits signal to", "signal to the", "to the nucleus", "activated notch1 transmits signal", "notch1 transmits signal to", "transmits signal to the", "signal to the nucleus", "activated notch1 transmits signal to", "notch1 transmits signal to the", "transmits signal to the nucleus", "mature notch1", "notch1 heterodimer", "heterodimer on", "on the", "the cell", "cell surface", "surface is", "is activated", "activated by", "by one", "one of", "of its", "its ligands:", "ligands: dll1", "cordle et", "et al.", "al. 2008", "jarriault et", "al. 1998", "benedito et", "al. 2009", "li et", "or jag2", "luo et", "al. 1997", "shimizu et", "al. 2000", "expressed in", "in trans", "trans on", "on a", "a neighboring", "neighboring cell.", "cell. thus", "a ligand", "ligand expressing", "expressing cell", "cell is", "is a", "a signal", "signal sending", "sending cell", "while the", "the notch1", "notch1 expressing", "signal receiving", "receiving cell.", "cell. if", "if notch1", "notch1 has", "has undergone", "undergone fringe", "fringe modification", "modification in", "in the", "the golgi", "it is", "is preferentially", "preferentially activated", "by delta", "delta ligands", "yang et", "al. 2005", "dll1 and", "and dll4.", "dll4.


upon", "


upon binding", "binding to", "to notch1", "notch1 on", "neighboring cell", "notch ligands", "ligands are", "are ubiquitinated", "ubiquitinated by", "by mindbomb", "mib1 and", "and mib2", "and/or neuralized", "neurl and", "and neurl1b", "e3 ubiquitin", "ubiquitin ligases", "ligases and", "and endocytosed", "koo et", "al. 2007", "itoh et", "al. 2003", "lai et", "al. 2001", "koutelou et", "song et", "al. 2006", "2006 .", ". endocytosis", "endocytosis of", "of ubiquitinated", "ubiquitinated ligands", "ligands is", "is thought", "thought to", "to mechanically", "mechanically stretch", "stretch the", "the bound", "bound notch1", "notch1 receptor", "exposing a", "a cleavage", "cleavage site", "site s2", "s2 that", "that is", "is recognized", "recognized by", "by adam10", "adam10 and/or", "and/or adam17", "adam17 metalloprotease", "van tetering", "tetering et", "brou et", "hartmann et", "al. 2002", "pan et", "1997 .", ". s2", "s2 cleavage", "cleavage of", "of notch1", "notch1 produces", "produces the", "the next1", "next1 fragment", "fragment which", "which is", "is further", "further cleaved", "cleaved at", "at an", "an s3", "s3 cleavage", "site by", "by the", "the gamma", "gamma secretase", "secretase complex", "resulting in", "in release", "release of", "of the", "notch1 intracellular", "intracellular domain", "into the", "the cytosol", "de strooper", "strooper et", "al. 1999", "schroeter et", "huppert et", "2000 .", ". nicd1", "nicd1 produced", "produced by", "by activation", "activation of", "notch1 in", "in response", "response to", "to in", "trans presented", "presented delta", "delta and", "and jagged", "jagged ligands", "traffics to", "nucleus where", "where it", "it acts", "acts as", "as a", "a transcription", "transcription regulator.


notch1", "regulator.


notch1 signaling", "signaling can", "can also", "also be", "be activated", "by ligands", "ligands other", "other than", "than dll1", "jag1 and", "and jag2.", "jag2. cntn1", "contactin 1", "transiently expressed", "expressed during", "during central", "central and", "and peripheral", "peripheral nervous", "nervous system", "system development", "activates notch1", "notch1 and", "and notch2", "notch2 in", "promoting oligodendrocyte", "oligodendrocyte maturation", "maturation and", "and myelination", "hu et", "2003 .", ". dner", "and notch", "notch like", "like epidermal", "epidermal growth", "growth factor", "factor related", "related receptor", "a transmembrane", "transmembrane protein", "protein specifically", "specifically expressed", "in dendrites", "dendrites and", "and cell", "cell bodies", "bodies of", "of postmitotic", "postmitotic neurons.", "neurons. activation", "notch1 by", "by dner", "dner in", "trans may", "may play", "play an", "an important", "important role", "role in", "in development", "development of", "the central", "central nervous", "system by", "by influencing", "influencing differentiation", "differentiation of", "of astrocytes", "eiraku et", "2005 .", ". activation", "by both", "both cntn1", "cntn1 and", "and dner", "dner is", "is deltex", "dependent and", "and results", "results in", "in gamma", "secretase mediated", "mediated release", "of nicd1.", "nicd1. three", "three members", "members of", "the deltex", "deltex protein", "protein family:", "family: dtx1", "dtx2 and", "and dtx4", "dtx4 possess", "possess a", "a domain", "domain involved", "involved in", "in binding", "binding cdc10/ankyrin", "cdc10/ankyrin repeats", "repeats of", "of notch.", "notch. dtx", "dtx proteins", "proteins are", "are considered", "considered as", "as positive", "positive regulators", "regulators of", "of notch", "notch signaling", "although the", "the exact", "exact mechanism", "mechanism has", "has not", "not been", "been elucidated", "matsuno et", "kishi et", "2001 .in", ".in addition", "dtx can", "can mediate", "mediate downregulation", "downregulation of", "signaling by", "by recruiting", "recruiting non", "non visual", "visual beta", "beta arrestins", "arrestins to", "to notch", "mukherjee et", "thereby trigerring", "trigerring notch", "notch ubiquitination.", "ubiquitination. dtx", "are negatively", "negatively regulated", "regulated by", "by itch", "ubiquitin ligase", "chastagner et", "2006 .

notch1", ".

notch1 signaling", "signaling in", "the signal", "receiving cell", "cell can", "can be", "be turned", "turned off", "off in", "in cis", "cis by", "by expression", "expression of", "ligands dll/jag", "sprinzak et", "al. 2010", "as well", "well as", "as dlk1", "baladron et", "bray et", "2008 .", ". formation", "formation of", "of notch1:ligand", "notch1:ligand complexes", "complexes in", "cis prevents", "prevents interaction", "interaction of", "notch1 with", "with ligands", "ligands expressed", "the inhibition", "inhibition of", "notch signaling.", "signaling. in", "be negatively", "the protein", "protein numb", "is asymmetrically", "asymmetrically distributed", "distributed during", "during cell", "cell division", "rhyu et", "al. 1994", "1994 .", ". numb", "numb recruits", "recruits itch", "itch ubiquitin", "ligase to", "and promotes", "promotes sorting", "sorting of", "notch1 through", "through late", "late endosomes", "endosomes for", "for degradation", "mcgill et", "mature notch1 heterodimer", "notch1 heterodimer on", "heterodimer on the", "on the cell", "the cell surface", "cell surface is", "surface is activated", "is activated by", "activated by one", "by one of", "one of its", "of its ligands:", "its ligands: dll1", "dll1 cordle", "cordle et al.", "et al. 2008", "2008 jarriault", "jarriault et al.", "et al. 1998", "dll4 benedito", "benedito et al.", "et al. 2009", "jag1 li", "li et al.", "1998 benedito", "2009 or", "jag2 luo", "luo et al.", "et al. 1997", "1997 shimizu", "shimizu et al.", "et al. 2000", "expressed in trans", "in trans on", "trans on a", "on a neighboring", "a neighboring cell.", "neighboring cell. thus", "thus a", "a ligand expressing", "ligand expressing cell", "expressing cell is", "cell is a", "is a signal", "a signal sending", "signal sending cell", "cell while", "while the notch1", "the notch1 expressing", "notch1 expressing cell", "a signal receiving", "signal receiving cell.", "receiving cell. if", "cell. if notch1", "if notch1 has", "notch1 has undergone", "has undergone fringe", "undergone fringe modification", "fringe modification in", "modification in the", "in the golgi", "golgi it", "it is preferentially", "is preferentially activated", "preferentially activated by", "activated by delta", "by delta ligands", "ligands yang", "yang et al.", "et al. 2005", "dll1 and dll4.", "and dll4.


upon", "dll4.


upon binding", "


upon binding to", "binding to notch1", "to notch1 on", "notch1 on a", "a neighboring cell", "cell notch", "notch ligands are", "ligands are ubiquitinated", "are ubiquitinated by", "ubiquitinated by mindbomb", "mindbomb mib1", "mib1 and mib2", "mib2 and/or", "neuralized neurl", "neurl and neurl1b", "neurl1b e3", "e3 ubiquitin ligases", "ubiquitin ligases and", "ligases and endocytosed", "endocytosed koo", "koo et al.", "et al. 2007", "2007 koo", "2005 itoh", "itoh et al.", "et al. 2003", "2003 lai", "lai et al.", "et al. 2001", "2001 koutelou", "koutelou et al.", "2008 song", "song et al.", "et al. 2006", "al. 2006 .", "2006 . endocytosis", ". endocytosis of", "endocytosis of ubiquitinated", "of ubiquitinated ligands", "ubiquitinated ligands is", "ligands is thought", "is thought to", "thought to mechanically", "to mechanically stretch", "mechanically stretch the", "stretch the bound", "the bound notch1", "bound notch1 receptor", "receptor exposing", "exposing a cleavage", "a cleavage site", "cleavage site s2", "site s2 that", "s2 that is", "that is recognized", "is recognized by", "recognized by adam10", "by adam10 and/or", "adam10 and/or adam17", "and/or adam17 metalloprotease", "metalloprotease van", "van tetering et", "tetering et al.", "2009 brou", "brou et al.", "2000 hartmann", "hartmann et al.", "et al. 2002", "2002 pan", "pan et al.", "al. 1997 .", "1997 . s2", ". s2 cleavage", "s2 cleavage of", "cleavage of notch1", "of notch1 produces", "notch1 produces the", "produces the next1", "the next1 fragment", "next1 fragment which", "fragment which is", "which is further", "is further cleaved", "further cleaved at", "cleaved at an", "at an s3", "an s3 cleavage", "s3 cleavage site", "cleavage site by", "site by the", "by the gamma", "the gamma secretase", "gamma secretase complex", "complex resulting", "resulting in release", "in release of", "release of the", "of the notch1", "the notch1 intracellular", "notch1 intracellular domain", "domain nicd1", "nicd1 into", "into the cytosol", "cytosol de", "de strooper et", "strooper et al.", "et al. 1999", "1999 schroeter", "schroeter et al.", "1998 huppert", "huppert et al.", "al. 2000 .", "2000 . nicd1", ". nicd1 produced", "nicd1 produced by", "produced by activation", "by activation of", "activation of notch1", "of notch1 in", "notch1 in response", "in response to", "response to in", "to in trans", "in trans presented", "trans presented delta", "presented delta and", "delta and jagged", "and jagged ligands", "dll/jag traffics", "traffics to the", "the nucleus where", "nucleus where it", "where it acts", "it acts as", "acts as a", "as a transcription", "a transcription regulator.


notch1", "transcription regulator.


notch1 signaling", "regulator.


notch1 signaling can", "signaling can also", "can also be", "also be activated", "be activated by", "activated by ligands", "by ligands other", "ligands other than", "other than dll1", "dll1 dll4", "dll4 jag1", "jag1 and jag2.", "and jag2. cntn1", "cntn1 contactin", "transiently expressed during", "expressed during central", "during central and", "central and peripheral", "and peripheral nervous", "peripheral nervous system", "nervous system development", "development activates", "activates notch1 and", "notch1 and notch2", "and notch2 in", "notch2 in trans", "trans promoting", "promoting oligodendrocyte maturation", "oligodendrocyte maturation and", "maturation and myelination", "myelination hu", "hu et al.", "al. 2003 .", "2003 . dner", "dner delta", "delta and notch", "and notch like", "notch like epidermal", "like epidermal growth", "epidermal growth factor", "growth factor related", "factor related receptor", "receptor is", "is a transmembrane", "a transmembrane protein", "transmembrane protein specifically", "protein specifically expressed", "specifically expressed in", "expressed in dendrites", "in dendrites and", "dendrites and cell", "and cell bodies", "cell bodies of", "bodies of postmitotic", "of postmitotic neurons.", "postmitotic neurons. activation", "neurons. activation of", "of notch1 by", "notch1 by dner", "by dner in", "dner in trans", "in trans may", "trans may play", "may play an", "play an important", "an important role", "important role in", "role in development", "in development of", "development of the", "of the central", "the central nervous", "central nervous system", "nervous system by", "system by influencing", "by influencing differentiation", "influencing differentiation of", "differentiation of astrocytes", "astrocytes eiraku", "eiraku et al.", "al. 2005 .", "2005 . activation", ". activation of", "notch1 by both", "by both cntn1", "both cntn1 and", "cntn1 and dner", "and dner is", "dner is deltex", "deltex dtx", "dtx dependent", "dependent and results", "and results in", "results in gamma", "in gamma secretase", "gamma secretase mediated", "secretase mediated release", "mediated release of", "release of nicd1.", "of nicd1. three", "nicd1. three members", "three members of", "members of the", "of the deltex", "the deltex protein", "deltex protein family:", "protein family: dtx1", "dtx1 dtx2", "dtx2 and dtx4", "and dtx4 possess", "dtx4 possess a", "possess a domain", "a domain involved", "domain involved in", "involved in binding", "in binding cdc10/ankyrin", "binding cdc10/ankyrin repeats", "cdc10/ankyrin repeats of", "repeats of notch.", "of notch. dtx", "notch. dtx proteins", "dtx proteins are", "proteins are considered", "are considered as", "considered as positive", "as positive regulators", "positive regulators of", "regulators of notch", "of notch signaling", "signaling although", "although the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "has not been", "not been elucidated", "elucidated matsuno", "matsuno et al.", "1998 kishi", "kishi et al.", "al. 2001 .in", "2001 .in addition", "addition dtx", "dtx can mediate", "can mediate downregulation", "mediate downregulation of", "downregulation of notch", "notch signaling by", "signaling by recruiting", "by recruiting non", "recruiting non visual", "non visual beta", "visual beta arrestins", "beta arrestins to", "arrestins to notch", "notch mukherjee", "mukherjee et al.", "thereby trigerring notch", "trigerring notch ubiquitination.", "notch ubiquitination. dtx", "ubiquitination. dtx proteins", "proteins are negatively", "are negatively regulated", "negatively regulated by", "regulated by itch", "itch aip4", "aip4 ubiquitin", "ligase chastagner", "chastagner et al.", "al. 2006 .

notch1", "2006 .

notch1 signaling", ".

notch1 signaling in", "signaling in the", "in the signal", "the signal receiving", "signal receiving cell", "receiving cell can", "cell can be", "can be turned", "be turned off", "turned off in", "off in cis", "in cis by", "cis by expression", "by expression of", "expression of notch", "of notch ligands", "notch ligands dll/jag", "dll/jag cordle", "2008 sprinzak", "sprinzak et al.", "et al. 2010", "as well as", "well as dlk1", "dlk1 baladron", "baladron et al.", "2005 bray", "bray et al.", "al. 2008 .", "2008 . formation", ". formation of", "formation of notch1:ligand", "of notch1:ligand complexes", "notch1:ligand complexes in", "complexes in cis", "in cis prevents", "cis prevents interaction", "prevents interaction of", "interaction of notch1", "of notch1 with", "notch1 with ligands", "with ligands expressed", "ligands expressed in", "trans resulting", "resulting in the", "in the inhibition", "the inhibition of", "inhibition of notch", "of notch signaling.", "notch signaling. in", "signaling. in the", "the signal sending", "notch signaling can", "signaling can be", "can be negatively", "be negatively regulated", "regulated by the", "by the protein", "the protein numb", "numb which", "which is asymmetrically", "is asymmetrically distributed", "asymmetrically distributed during", "distributed during cell", "during cell division", "division rhyu", "rhyu et al.", "et al. 1994", "al. 1994 .", "1994 . numb", ". numb recruits", "numb recruits itch", "recruits itch ubiquitin", "itch ubiquitin ligase", "ubiquitin ligase to", "ligase to notch1", "to notch1 and", "notch1 and promotes", "and promotes sorting", "promotes sorting of", "sorting of notch1", "of notch1 through", "notch1 through late", "through late endosomes", "late endosomes for", "endosomes for degradation", "degradation mcgill", "mcgill et al.", "2009 chastagner", "mature notch1 heterodimer on", "notch1 heterodimer on the", "heterodimer on the cell", "on the cell surface", "the cell surface is", "cell surface is activated", "surface is activated by", "is activated by one", "activated by one of", "by one of its", "one of its ligands:", "of its ligands: dll1", "ligands: dll1 cordle", "dll1 cordle et", "cordle et al. 2008", "al. 2008 jarriault", "2008 jarriault et", "jarriault et al. 1998", "1998 dll4", "dll4 benedito et", "benedito et al. 2009", "2009 jag1", "jag1 li et", "li et al. 1998", "al. 1998 benedito", "1998 benedito et", "al. 2009 or", "2009 or jag2", "or jag2 luo", "jag2 luo et", "luo et al. 1997", "al. 1997 shimizu", "1997 shimizu et", "shimizu et al. 2000", "2000 expressed", "expressed in trans on", "in trans on a", "trans on a neighboring", "on a neighboring cell.", "a neighboring cell. thus", "cell. thus a", "thus a ligand", "a ligand expressing cell", "ligand expressing cell is", "expressing cell is a", "cell is a signal", "is a signal sending", "a signal sending cell", "sending cell while", "cell while the", "while the notch1 expressing", "the notch1 expressing cell", "notch1 expressing cell is", "is a signal receiving", "a signal receiving cell.", "signal receiving cell. if", "receiving cell. if notch1", "cell. if notch1 has", "if notch1 has undergone", "notch1 has undergone fringe", "has undergone fringe modification", "undergone fringe modification in", "fringe modification in the", "modification in the golgi", "the golgi it", "golgi it is", "it is preferentially activated", "is preferentially activated by", "preferentially activated by delta", "activated by delta ligands", "delta ligands yang", "ligands yang et", "yang et al. 2005", "2005 dll1", "dll1 and dll4.


upon", "and dll4.


upon binding", "dll4.


upon binding to", "


upon binding to notch1", "binding to notch1 on", "to notch1 on a", "notch1 on a neighboring", "on a neighboring cell", "neighboring cell notch", "cell notch ligands", "notch ligands are ubiquitinated", "ligands are ubiquitinated by", "are ubiquitinated by mindbomb", "by mindbomb mib1", "mindbomb mib1 and", "and mib2 and/or", "mib2 and/or neuralized", "and/or neuralized neurl", "neuralized neurl and", "and neurl1b e3", "neurl1b e3 ubiquitin", "e3 ubiquitin ligases and", "ubiquitin ligases and endocytosed", "and endocytosed koo", "endocytosed koo et", "koo et al. 2007", "al. 2007 koo", "2007 koo et", "koo et al. 2005", "al. 2005 itoh", "2005 itoh et", "itoh et al. 2003", "al. 2003 lai", "2003 lai et", "lai et al. 2001", "al. 2001 koutelou", "2001 koutelou et", "koutelou et al. 2008", "al. 2008 song", "2008 song et", "song et al. 2006", "et al. 2006 .", "al. 2006 . endocytosis", "2006 . endocytosis of", ". endocytosis of ubiquitinated", "endocytosis of ubiquitinated ligands", "of ubiquitinated ligands is", "ubiquitinated ligands is thought", "ligands is thought to", "is thought to mechanically", "thought to mechanically stretch", "to mechanically stretch the", "mechanically stretch the bound", "stretch the bound notch1", "the bound notch1 receptor", "notch1 receptor exposing", "receptor exposing a", "exposing a cleavage site", "a cleavage site s2", "cleavage site s2 that", "site s2 that is", "s2 that is recognized", "that is recognized by", "is recognized by adam10", "recognized by adam10 and/or", "by adam10 and/or adam17", "adam10 and/or adam17 metalloprotease", "adam17 metalloprotease van", "metalloprotease van tetering", "van tetering et al.", "tetering et al. 2009", "al. 2009 brou", "2009 brou et", "brou et al. 2000", "al. 2000 hartmann", "2000 hartmann et", "hartmann et al. 2002", "al. 2002 pan", "2002 pan et", "pan et al. 1997", "et al. 1997 .", "al. 1997 . s2", "1997 . s2 cleavage", ". s2 cleavage of", "s2 cleavage of notch1", "cleavage of notch1 produces", "of notch1 produces the", "notch1 produces the next1", "produces the next1 fragment", "the next1 fragment which", "next1 fragment which is", "fragment which is further", "which is further cleaved", "is further cleaved at", "further cleaved at an", "cleaved at an s3", "at an s3 cleavage", "an s3 cleavage site", "s3 cleavage site by", "cleavage site by the", "site by the gamma", "by the gamma secretase", "the gamma secretase complex", "secretase complex resulting", "complex resulting in", "resulting in release of", "in release of the", "release of the notch1", "of the notch1 intracellular", "the notch1 intracellular domain", "intracellular domain nicd1", "nicd1 into the", "the cytosol de", "cytosol de strooper", "de strooper et al.", "strooper et al. 1999", "al. 1999 schroeter", "1999 schroeter et", "schroeter et al. 1998", "al. 1998 huppert", "1998 huppert et", "huppert et al. 2000", "et al. 2000 .", "al. 2000 . nicd1", "2000 . nicd1 produced", ". nicd1 produced by", "nicd1 produced by activation", "produced by activation of", "by activation of notch1", "activation of notch1 in", "of notch1 in response", "notch1 in response to", "in response to in", "response to in trans", "to in trans presented", "in trans presented delta", "trans presented delta and", "presented delta and jagged", "delta and jagged ligands", "jagged ligands dll/jag", "dll/jag traffics to", "traffics to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it acts", "where it acts as", "it acts as a", "acts as a transcription", "as a transcription regulator.


notch1", "a transcription regulator.


notch1 signaling", "transcription regulator.


notch1 signaling can", "regulator.


notch1 signaling can also", "signaling can also be", "can also be activated", "also be activated by", "be activated by ligands", "activated by ligands other", "by ligands other than", "ligands other than dll1", "than dll1 dll4", "dll4 jag1 and", "jag1 and jag2. cntn1", "jag2. cntn1 contactin", "cntn1 contactin 1", "1 transiently", "transiently expressed during central", "expressed during central and", "during central and peripheral", "central and peripheral nervous", "and peripheral nervous system", "peripheral nervous system development", "system development activates", "development activates notch1", "activates notch1 and notch2", "notch1 and notch2 in", "and notch2 in trans", "in trans promoting", "trans promoting oligodendrocyte", "promoting oligodendrocyte maturation and", "oligodendrocyte maturation and myelination", "and myelination hu", "myelination hu et", "hu et al. 2003", "et al. 2003 .", "al. 2003 . dner", ". dner delta", "dner delta and", "delta and notch like", "and notch like epidermal", "notch like epidermal growth", "like epidermal growth factor", "epidermal growth factor related", "growth factor related receptor", "related receptor is", "receptor is a", "is a transmembrane protein", "a transmembrane protein specifically", "transmembrane protein specifically expressed", "protein specifically expressed in", "specifically expressed in dendrites", "expressed in dendrites and", "in dendrites and cell", "dendrites and cell bodies", "and cell bodies of", "cell bodies of postmitotic", "bodies of postmitotic neurons.", "of postmitotic neurons. activation", "postmitotic neurons. activation of", "neurons. activation of notch1", "activation of notch1 by", "of notch1 by dner", "notch1 by dner in", "by dner in trans", "dner in trans may", "in trans may play", "trans may play an", "may play an important", "play an important role", "an important role in", "important role in development", "role in development of", "in development of the", "development of the central", "of the central nervous", "the central nervous system", "central nervous system by", "nervous system by influencing", "system by influencing differentiation", "by influencing differentiation of", "influencing differentiation of astrocytes", "of astrocytes eiraku", "astrocytes eiraku et", "eiraku et al. 2005", "et al. 2005 .", "al. 2005 . activation", "2005 . activation of", ". activation of notch1", "of notch1 by both", "notch1 by both cntn1", "by both cntn1 and", "both cntn1 and dner", "cntn1 and dner is", "and dner is deltex", "is deltex dtx", "dtx dependent and", "dependent and results in", "and results in gamma", "results in gamma secretase", "in gamma secretase mediated", "gamma secretase mediated release", "secretase mediated release of", "mediated release of nicd1.", "release of nicd1. three", "of nicd1. three members", "nicd1. three members of", "three members of the", "members of the deltex", "of the deltex protein", "the deltex protein family:", "deltex protein family: dtx1", "family: dtx1 dtx2", "dtx1 dtx2 and", "dtx2 and dtx4 possess", "and dtx4 possess a", "dtx4 possess a domain", "possess a domain involved", "a domain involved in", "domain involved in binding", "involved in binding cdc10/ankyrin", "in binding cdc10/ankyrin repeats", "binding cdc10/ankyrin repeats of", "cdc10/ankyrin repeats of notch.", "repeats of notch. dtx", "of notch. dtx proteins", "notch. dtx proteins are", "dtx proteins are considered", "proteins are considered as", "are considered as positive", "considered as positive regulators", "as positive regulators of", "positive regulators of notch", "regulators of notch signaling", "notch signaling although", "signaling although the", "although the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been elucidated", "been elucidated matsuno", "elucidated matsuno et", "matsuno et al. 1998", "al. 1998 kishi", "1998 kishi et", "kishi et al. 2001", "et al. 2001 .in", "al. 2001 .in addition", ".in addition dtx", "addition dtx can", "dtx can mediate downregulation", "can mediate downregulation of", "mediate downregulation of notch", "downregulation of notch signaling", "of notch signaling by", "notch signaling by recruiting", "signaling by recruiting non", "by recruiting non visual", "recruiting non visual beta", "non visual beta arrestins", "visual beta arrestins to", "beta arrestins to notch", "to notch mukherjee", "notch mukherjee et", "mukherjee et al. 2005", "2005 thereby", "thereby trigerring notch ubiquitination.", "trigerring notch ubiquitination. dtx", "notch ubiquitination. dtx proteins", "ubiquitination. dtx proteins are", "dtx proteins are negatively", "proteins are negatively regulated", "are negatively regulated by", "negatively regulated by itch", "by itch aip4", "aip4 ubiquitin ligase", "ubiquitin ligase chastagner", "ligase chastagner et", "chastagner et al. 2006", "et al. 2006 .

notch1", "al. 2006 .

notch1 signaling", "2006 .

notch1 signaling in", ".

notch1 signaling in the", "signaling in the signal", "in the signal receiving", "the signal receiving cell", "signal receiving cell can", "receiving cell can be", "cell can be turned", "can be turned off", "be turned off in", "turned off in cis", "off in cis by", "in cis by expression", "cis by expression of", "by expression of notch", "expression of notch ligands", "of notch ligands dll/jag", "ligands dll/jag cordle", "dll/jag cordle et", "al. 2008 sprinzak", "2008 sprinzak et", "sprinzak et al. 2010", "2010 as", "as well as dlk1", "as dlk1 baladron", "dlk1 baladron et", "baladron et al. 2005", "al. 2005 bray", "2005 bray et", "bray et al. 2008", "et al. 2008 .", "al. 2008 . formation", "2008 . formation of", ". formation of notch1:ligand", "formation of notch1:ligand complexes", "of notch1:ligand complexes in", "notch1:ligand complexes in cis", "complexes in cis prevents", "in cis prevents interaction", "cis prevents interaction of", "prevents interaction of notch1", "interaction of notch1 with", "of notch1 with ligands", "notch1 with ligands expressed", "with ligands expressed in", "ligands expressed in trans", "in trans resulting", "trans resulting in", "resulting in the inhibition", "in the inhibition of", "the inhibition of notch", "inhibition of notch signaling.", "of notch signaling. in", "notch signaling. in the", "signaling. in the signal", "in the signal sending", "the signal sending cell", "sending cell notch", "cell notch signaling", "notch signaling can be", "signaling can be negatively", "can be negatively regulated", "be negatively regulated by", "negatively regulated by the", "regulated by the protein", "by the protein numb", "protein numb which", "numb which is", "which is asymmetrically distributed", "is asymmetrically distributed during", "asymmetrically distributed during cell", "distributed during cell division", "cell division rhyu", "division rhyu et", "rhyu et al. 1994", "et al. 1994 .", "al. 1994 . numb", "1994 . numb recruits", ". numb recruits itch", "numb recruits itch ubiquitin", "recruits itch ubiquitin ligase", "itch ubiquitin ligase to", "ubiquitin ligase to notch1", "ligase to notch1 and", "to notch1 and promotes", "notch1 and promotes sorting", "and promotes sorting of", "promotes sorting of notch1", "sorting of notch1 through", "of notch1 through late", "notch1 through late endosomes", "through late endosomes for", "late endosomes for degradation", "for degradation mcgill", "degradation mcgill et", "mcgill et al. 2009", "al. 2009 chastagner", "2009 chastagner et", "chastagner et al. 2008", "mature notch1 heterodimer on the", "notch1 heterodimer on the cell", "heterodimer on the cell surface", "on the cell surface is", "the cell surface is activated", "cell surface is activated by", "surface is activated by one", "is activated by one of", "activated by one of its", "by one of its ligands:", "one of its ligands: dll1", "its ligands: dll1 cordle", "ligands: dll1 cordle et", "dll1 cordle et al.", "et al. 2008 jarriault", "al. 2008 jarriault et", "2008 jarriault et al.", "al. 1998 dll4", "dll4 benedito et al.", "al. 2009 jag1", "jag1 li et al.", "et al. 1998 benedito", "al. 1998 benedito et", "1998 benedito et al.", "et al. 2009 or", "al. 2009 or jag2", "or jag2 luo et", "jag2 luo et al.", "et al. 1997 shimizu", "al. 1997 shimizu et", "1997 shimizu et al.", "al. 2000 expressed", "2000 expressed in", "expressed in trans on a", "in trans on a neighboring", "trans on a neighboring cell.", "on a neighboring cell. thus", "neighboring cell. thus a", "cell. thus a ligand", "thus a ligand expressing", "a ligand expressing cell is", "ligand expressing cell is a", "expressing cell is a signal", "cell is a signal sending", "is a signal sending cell", "signal sending cell while", "sending cell while the", "cell while the notch1", "while the notch1 expressing cell", "the notch1 expressing cell is", "notch1 expressing cell is a", "cell is a signal receiving", "is a signal receiving cell.", "a signal receiving cell. if", "signal receiving cell. if notch1", "receiving cell. if notch1 has", "cell. if notch1 has undergone", "if notch1 has undergone fringe", "notch1 has undergone fringe modification", "has undergone fringe modification in", "undergone fringe modification in the", "fringe modification in the golgi", "in the golgi it", "the golgi it is", "golgi it is preferentially", "it is preferentially activated by", "is preferentially activated by delta", "preferentially activated by delta ligands", "by delta ligands yang", "delta ligands yang et", "ligands yang et al.", "al. 2005 dll1", "2005 dll1 and", "dll1 and dll4.


upon binding", "and dll4.


upon binding to", "dll4.


upon binding to notch1", "


upon binding to notch1 on", "binding to notch1 on a", "to notch1 on a neighboring", "notch1 on a neighboring cell", "a neighboring cell notch", "neighboring cell notch ligands", "cell notch ligands are", "notch ligands are ubiquitinated by", "ligands are ubiquitinated by mindbomb", "ubiquitinated by mindbomb mib1", "by mindbomb mib1 and", "mindbomb mib1 and mib2", "mib1 and mib2 and/or", "and mib2 and/or neuralized", "and/or neuralized neurl and", "neuralized neurl and neurl1b", "neurl and neurl1b e3", "and neurl1b e3 ubiquitin", "neurl1b e3 ubiquitin ligases", "e3 ubiquitin ligases and endocytosed", "ligases and endocytosed koo", "and endocytosed koo et", "endocytosed koo et al.", "et al. 2007 koo", "al. 2007 koo et", "2007 koo et al.", "et al. 2005 itoh", "al. 2005 itoh et", "2005 itoh et al.", "et al. 2003 lai", "al. 2003 lai et", "2003 lai et al.", "et al. 2001 koutelou", "al. 2001 koutelou et", "2001 koutelou et al.", "et al. 2008 song", "al. 2008 song et", "2008 song et al.", "song et al. 2006 .", "et al. 2006 . endocytosis", "al. 2006 . endocytosis of", "2006 . endocytosis of ubiquitinated", ". endocytosis of ubiquitinated ligands", "endocytosis of ubiquitinated ligands is", "of ubiquitinated ligands is thought", "ubiquitinated ligands is thought to", "ligands is thought to mechanically", "is thought to mechanically stretch", "thought to mechanically stretch the", "to mechanically stretch the bound", "mechanically stretch the bound notch1", "stretch the bound notch1 receptor", "bound notch1 receptor exposing", "notch1 receptor exposing a", "receptor exposing a cleavage", "exposing a cleavage site s2", "a cleavage site s2 that", "cleavage site s2 that is", "site s2 that is recognized", "s2 that is recognized by", "that is recognized by adam10", "is recognized by adam10 and/or", "recognized by adam10 and/or adam17", "by adam10 and/or adam17 metalloprotease", "and/or adam17 metalloprotease van", "adam17 metalloprotease van tetering", "metalloprotease van tetering et", "van tetering et al. 2009", "et al. 2009 brou", "al. 2009 brou et", "2009 brou et al.", "et al. 2000 hartmann", "al. 2000 hartmann et", "2000 hartmann et al.", "et al. 2002 pan", "al. 2002 pan et", "2002 pan et al.", "pan et al. 1997 .", "et al. 1997 . s2", "al. 1997 . s2 cleavage", "1997 . s2 cleavage of", ". s2 cleavage of notch1", "s2 cleavage of notch1 produces", "cleavage of notch1 produces the", "of notch1 produces the next1", "notch1 produces the next1 fragment", "produces the next1 fragment which", "the next1 fragment which is", "next1 fragment which is further", "fragment which is further cleaved", "which is further cleaved at", "is further cleaved at an", "further cleaved at an s3", "cleaved at an s3 cleavage", "at an s3 cleavage site", "an s3 cleavage site by", "s3 cleavage site by the", "cleavage site by the gamma", "site by the gamma secretase", "by the gamma secretase complex", "gamma secretase complex resulting", "secretase complex resulting in", "complex resulting in release", "resulting in release of the", "in release of the notch1", "release of the notch1 intracellular", "of the notch1 intracellular domain", "notch1 intracellular domain nicd1", "domain nicd1 into", "nicd1 into the cytosol", "into the cytosol de", "the cytosol de strooper", "cytosol de strooper et", "de strooper et al. 1999", "et al. 1999 schroeter", "al. 1999 schroeter et", "1999 schroeter et al.", "et al. 1998 huppert", "al. 1998 huppert et", "1998 huppert et al.", "huppert et al. 2000 .", "et al. 2000 . nicd1", "al. 2000 . nicd1 produced", "2000 . nicd1 produced by", ". nicd1 produced by activation", "nicd1 produced by activation of", "produced by activation of notch1", "by activation of notch1 in", "activation of notch1 in response", "of notch1 in response to", "notch1 in response to in", "in response to in trans", "response to in trans presented", "to in trans presented delta", "in trans presented delta and", "trans presented delta and jagged", "presented delta and jagged ligands", "and jagged ligands dll/jag", "ligands dll/jag traffics", "dll/jag traffics to the", "traffics to the nucleus where", "to the nucleus where it", "the nucleus where it acts", "nucleus where it acts as", "where it acts as a", "it acts as a transcription", "acts as a transcription regulator.


notch1", "as a transcription regulator.


notch1 signaling", "a transcription regulator.


notch1 signaling can", "transcription regulator.


notch1 signaling can also", "regulator.


notch1 signaling can also be", "signaling can also be activated", "can also be activated by", "also be activated by ligands", "be activated by ligands other", "activated by ligands other than", "by ligands other than dll1", "other than dll1 dll4", "dll1 dll4 jag1", "dll4 jag1 and jag2.", "and jag2. cntn1 contactin", "jag2. cntn1 contactin 1", "contactin 1 transiently", "1 transiently expressed", "transiently expressed during central and", "expressed during central and peripheral", "during central and peripheral nervous", "central and peripheral nervous system", "and peripheral nervous system development", "nervous system development activates", "system development activates notch1", "development activates notch1 and", "activates notch1 and notch2 in", "notch1 and notch2 in trans", "notch2 in trans promoting", "in trans promoting oligodendrocyte", "trans promoting oligodendrocyte maturation", "promoting oligodendrocyte maturation and myelination", "maturation and myelination hu", "and myelination hu et", "myelination hu et al.", "hu et al. 2003 .", "et al. 2003 . dner", "2003 . dner delta", ". dner delta and", "dner delta and notch", "delta and notch like epidermal", "and notch like epidermal growth", "notch like epidermal growth factor", "like epidermal growth factor related", "epidermal growth factor related receptor", "factor related receptor is", "related receptor is a", "receptor is a transmembrane", "is a transmembrane protein specifically", "a transmembrane protein specifically expressed", "transmembrane protein specifically expressed in", "protein specifically expressed in dendrites", "specifically expressed in dendrites and", "expressed in dendrites and cell", "in dendrites and cell bodies", "dendrites and cell bodies of", "and cell bodies of postmitotic", "cell bodies of postmitotic neurons.", "bodies of postmitotic neurons. activation", "of postmitotic neurons. activation of", "postmitotic neurons. activation of notch1", "neurons. activation of notch1 by", "activation of notch1 by dner", "of notch1 by dner in", "notch1 by dner in trans", "by dner in trans may", "dner in trans may play", "in trans may play an", "trans may play an important", "may play an important role", "play an important role in", "an important role in development", "important role in development of", "role in development of the", "in development of the central", "development of the central nervous", "of the central nervous system", "the central nervous system by", "central nervous system by influencing", "nervous system by influencing differentiation", "system by influencing differentiation of", "by influencing differentiation of astrocytes", "differentiation of astrocytes eiraku", "of astrocytes eiraku et", "astrocytes eiraku et al.", "eiraku et al. 2005 .", "et al. 2005 . activation", "al. 2005 . activation of", "2005 . activation of notch1", ". activation of notch1 by", "activation of notch1 by both", "of notch1 by both cntn1", "notch1 by both cntn1 and", "by both cntn1 and dner", "both cntn1 and dner is", "cntn1 and dner is deltex", "dner is deltex dtx", "deltex dtx dependent", "dtx dependent and results", "dependent and results in gamma", "and results in gamma secretase", "results in gamma secretase mediated", "in gamma secretase mediated release", "gamma secretase mediated release of", "secretase mediated release of nicd1.", "mediated release of nicd1. three", "release of nicd1. three members", "of nicd1. three members of", "nicd1. three members of the", "three members of the deltex", "members of the deltex protein", "of the deltex protein family:", "the deltex protein family: dtx1", "protein family: dtx1 dtx2", "family: dtx1 dtx2 and", "dtx1 dtx2 and dtx4", "dtx2 and dtx4 possess a", "and dtx4 possess a domain", "dtx4 possess a domain involved", "possess a domain involved in", "a domain involved in binding", "domain involved in binding cdc10/ankyrin", "involved in binding cdc10/ankyrin repeats", "in binding cdc10/ankyrin repeats of", "binding cdc10/ankyrin repeats of notch.", "cdc10/ankyrin repeats of notch. dtx", "repeats of notch. dtx proteins", "of notch. dtx proteins are", "notch. dtx proteins are considered", "dtx proteins are considered as", "proteins are considered as positive", "are considered as positive regulators", "considered as positive regulators of", "as positive regulators of notch", "positive regulators of notch signaling", "of notch signaling although", "notch signaling although the", "signaling although the exact", "although the exact mechanism has", "the exact mechanism has not", "exact mechanism has not been", "mechanism has not been elucidated", "not been elucidated matsuno", "been elucidated matsuno et", "elucidated matsuno et al.", "et al. 1998 kishi", "al. 1998 kishi et", "1998 kishi et al.", "kishi et al. 2001 .in", "et al. 2001 .in addition", "2001 .in addition dtx", ".in addition dtx can", "addition dtx can mediate", "dtx can mediate downregulation of", "can mediate downregulation of notch", "mediate downregulation of notch signaling", "downregulation of notch signaling by", "of notch signaling by recruiting", "notch signaling by recruiting non", "signaling by recruiting non visual", "by recruiting non visual beta", "recruiting non visual beta arrestins", "non visual beta arrestins to", "visual beta arrestins to notch", "arrestins to notch mukherjee", "to notch mukherjee et", "notch mukherjee et al.", "al. 2005 thereby", "2005 thereby trigerring", "thereby trigerring notch ubiquitination. dtx", "trigerring notch ubiquitination. dtx proteins", "notch ubiquitination. dtx proteins are", "ubiquitination. dtx proteins are negatively", "dtx proteins are negatively regulated", "proteins are negatively regulated by", "are negatively regulated by itch", "regulated by itch aip4", "itch aip4 ubiquitin", "ubiquitin ligase chastagner et", "ligase chastagner et al.", "chastagner et al. 2006 .

notch1", "et al. 2006 .

notch1 signaling", "al. 2006 .

notch1 signaling in", "2006 .

notch1 signaling in the", ".

notch1 signaling in the signal", "signaling in the signal receiving", "in the signal receiving cell", "the signal receiving cell can", "signal receiving cell can be", "receiving cell can be turned", "cell can be turned off", "can be turned off in", "be turned off in cis", "turned off in cis by", "off in cis by expression", "in cis by expression of", "cis by expression of notch", "by expression of notch ligands", "expression of notch ligands dll/jag", "notch ligands dll/jag cordle", "ligands dll/jag cordle et", "dll/jag cordle et al.", "et al. 2008 sprinzak", "al. 2008 sprinzak et", "2008 sprinzak et al.", "al. 2010 as", "2010 as well", "well as dlk1 baladron", "as dlk1 baladron et", "dlk1 baladron et al.", "et al. 2005 bray", "al. 2005 bray et", "2005 bray et al.", "bray et al. 2008 .", "et al. 2008 . formation", "al. 2008 . formation of", "2008 . formation of notch1:ligand", ". formation of notch1:ligand complexes", "formation of notch1:ligand complexes in", "of notch1:ligand complexes in cis", "notch1:ligand complexes in cis prevents", "complexes in cis prevents interaction", "in cis prevents interaction of", "cis prevents interaction of notch1", "prevents interaction of notch1 with", "interaction of notch1 with ligands", "of notch1 with ligands expressed", "notch1 with ligands expressed in", "with ligands expressed in trans", "expressed in trans resulting", "in trans resulting in", "trans resulting in the", "resulting in the inhibition of", "in the inhibition of notch", "the inhibition of notch signaling.", "inhibition of notch signaling. in", "of notch signaling. in the", "notch signaling. in the signal", "signaling. in the signal sending", "in the signal sending cell", "signal sending cell notch", "sending cell notch signaling", "cell notch signaling can", "notch signaling can be negatively", "signaling can be negatively regulated", "can be negatively regulated by", "be negatively regulated by the", "negatively regulated by the protein", "regulated by the protein numb", "the protein numb which", "protein numb which is", "numb which is asymmetrically", "which is asymmetrically distributed during", "is asymmetrically distributed during cell", "asymmetrically distributed during cell division", "during cell division rhyu", "cell division rhyu et", "division rhyu et al.", "rhyu et al. 1994 .", "et al. 1994 . numb", "al. 1994 . numb recruits", "1994 . numb recruits itch", ". numb recruits itch ubiquitin", "numb recruits itch ubiquitin ligase", "recruits itch ubiquitin ligase to", "itch ubiquitin ligase to notch1", "ubiquitin ligase to notch1 and", "ligase to notch1 and promotes", "to notch1 and promotes sorting", "notch1 and promotes sorting of", "and promotes sorting of notch1", "promotes sorting of notch1 through", "sorting of notch1 through late", "of notch1 through late endosomes", "notch1 through late endosomes for", "through late endosomes for degradation", "endosomes for degradation mcgill", "for degradation mcgill et", "degradation mcgill et al.", "et al. 2009 chastagner", "al. 2009 chastagner et", "2009 chastagner et al.", "chastagner et al. 2008 ." ] }, { "record_id": "GLY_000594_1_212", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "212436", "r hsa", "hsa 212436", "r hsa 212436" ] }, { "record_id": "GLY_000594_1_212", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "generic transcription", "transcription pathway", "generic transcription pathway", "overview of", "of transcription", "transcription regulation:", "

detailed studies", "studies of", "of gene", "gene transcription", "transcription regulation", "regulation in", "in a", "a wide", "wide variety", "variety of", "of eukaryotic", "eukaryotic systems", "systems has", "has revealed", "revealed the", "the general", "general principles", "principles and", "and mechanisms", "mechanisms by", "by which", "which cell", "or tissue", "tissue specific", "specific regulation", "regulation of", "of differential", "differential gene", "transcription is", "is mediated", "reviewed in", "in naar", "2001. kadonaga", "2006 .", "of the", "the three", "three major", "major classes", "classes of", "of dna", "dna polymerase", "polymerase involved", "involved in", "in eukaryotic", "eukaryotic gene", "polymerase ii", "ii generally", "generally regulates", "regulates protein", "protein encoding", "encoding genes.", "figure 1", "1 shows", "shows a", "a diagram", "diagram of", "the various", "various components", "components involved", "in cell", "cell specific", "of pol", "pol ii", "ii gene", "gene transcription.", "transcription.

core", "

core promoter:", "promoter: pol", "ii regulated", "regulated genes", "genes typically", "typically have", "have a", "a core", "core promoter", "promoter where", "where pol", "ii and", "and a", "a variety", "of general", "general factors", "factors bind", "bind to", "to specific", "specific dna", "dna motifs:", "motifs:
", "i: the", "the tata", "tata box", "tata dna", "dna sequence", "which is", "is bound", "bound by", "by the", "the \\tata", "\\tata binding", "binding protein\\", "tbp .
", "ii: the", "the initiator", "initiator motif", "and certain", "certain other", "other core", "core factors", "is present", "present in", "in many", "many pol", "regulated genes.
", "iii: the", "the downstream", "downstream promoter", "promoter element", "a subset", "subset of", "ii genes", "and where", "where additional", "additional core", "factors bind.", "
the core", "promoter binding", "binding factors", "factors are", "are generally", "generally ubiquitously", "ubiquitously expressed", "although there", "there are", "are exceptions", "exceptions to", "to this.

proximal", "this.

proximal promoter:", "promoter: immediately", "immediately upstream", "the core", "ii target", "target genes", "genes often", "often have", "a proximal", "proximal promoter", "promoter region", "region that", "that spans", "spans up", "up to", "to 500", "500 base", "base pairs", "or even", "even to", "to 1000", "1000 b.p..", "this region", "region contains", "contains a", "a number", "number of", "of functional", "functional dna", "dna binding", "binding sites", "sites for", "for a", "a specific", "specific set", "set of", "transcription activator", "and transcription", "transcription repressor", "these ta", "ta and", "and tr", "tr factors", "generally cell", "specific in", "in expression", "rather than", "than ubiquitous", "so that", "that the", "the presence", "presence of", "of their", "their cognate", "cognate binding", "sites in", "in the", "the proximal", "region programs", "programs cell", "specific expression", "expression of", "the target", "target gene", "perhaps in", "in conjunction", "conjunction with", "with ta", "tr complexes", "complexes bound", "bound in", "in distal", "distal enhancer", "enhancer regions.", "

distal enhancer", "enhancer s", "s :", ": many", "many or", "or most", "most pol", "genes in", "in higher", "higher eukaryotes", "eukaryotes have", "have one", "one or", "or more", "more distal", "enhancer regions", "regions which", "which are", "are essential", "essential for", "for proper", "proper regulation", "the gene", "often in", "a cell", "cell or", "specific pattern.", "like the", "each of", "the distal", "regions typically", "typically contain", "contain a", "a cluster", "cluster of", "of binding", "for specific", "specific ta", "ta and/or", "and/or tr", "tr dna", "than just", "just a", "a single", "single site.", "site.

", "enhancers generally", "generally have", "have three", "three defining", "defining characteristics:
", "i: they", "they can", "can be", "be located", "located very", "very long", "long distances", "distances from", "from the", "the promoter", "promoter of", "gene they", "they regulate", "sometimes as", "as far", "far as", "as 100", "100 kb", "or more.
", "ii: they", "be either", "either upstream", "or downstream", "including within", "within introns", "introns of", "of that", "that gene.
", "iii: they", "can function", "function in", "in either", "either orientation", "orientation in", "the dna.

combinatorial", "dna.

combinatorial mechanisms", "mechanisms of", "transcription regulation:", "regulation: the", "the specific", "specific combination", "combination of", "of ta", "tr binding", "sites within", "within the", "promoter and/or", "and/or distal", "provides a", "a \\combinatorial", "\\combinatorial transcription", "transcription code\\", "code\\ that", "that mediates", "mediates cell", "the associated", "associated target", "target gene.", "each promoter", "promoter or", "or enhancer", "enhancer region", "region mediates", "mediates expression", "expression in", "specific subset", "the overall", "overall expression", "expression pattern.", "in at", "at least", "least some", "some cases", "each enhancer", "region functions", "functions completely", "completely independently", "independently of", "the others", "expression pattern", "pattern is", "is a", "a linear", "linear combination", "the expression", "expression patterns", "patterns of", "of each", "the enhancer", "enhancer modules.

co", "modules.

co activator", "activator and", "and co", "co repressor", "repressor complexes:", "dna bound", "bound ta", "tr proteins", "proteins typically", "typically recruit", "recruit the", "the assembly", "assembly of", "of specific", "specific co", "co activator", "co a", "co r", "for regulating", "regulating target", "both co", "co a's", "a's and", "co r's", "are multi", "multi protein", "protein complexes", "complexes that", "that contain", "contain several", "several specific", "specific protein", "protein components.

co", "components.

co activator", "activator complexes", "complexes generally", "generally contain", "contain at", "at lease", "lease one", "one component", "component protein", "protein that", "that has", "has histone", "histone acetyl", "acetyl transferase", "enzymatic activity.", "this functions", "functions to", "to acetylate", "acetylate histones", "histones and/or", "and/or other", "other chromatin", "chromatin associated", "associated factors", "which typically", "typically increases", "increases that", "that transcription", "transcription activation", "activation of", "by contrast", "repressor complexes", "histone de", "de acetylase", "to de", "de acetylate", "associated factors.", "factors. this", "this typically", "increases the", "the transcription", "transcription repression", "repression of", "target gene.

adaptor", "complexes: in", "in addition", "addition to", "to the", "the co", "that assemble", "assemble on", "on particular", "particular cell", "ta factors", "are at", "least two", "two additional", "additional transcriptional", "transcriptional co", "complexes common", "common to", "to most", "most cells.", "one of", "of these", "these is", "is the", "the mediator", "mediator complex", "which functions", "functions as", "as an", "an \\adaptor\\", "\\adaptor\\ complex", "complex that", "that bridges", "bridges between", "between the", "the tissue", "complexes assembled", "assembled in", "or distal", "distal enhancers", "enhancers .", "the human", "human mediator", "complex has", "has been", "been shown", "shown to", "to contain", "least 19", "19 protein", "protein distinct", "distinct components.", "different combinations", "combinations of", "these co", "activator proteins", "proteins are", "are also", "also found", "found to", "to be", "be components", "components of", "specific transcription", "transcription co", "such as", "as the", "the drip", "trap and", "and arc", "arc complexes", "complexes described", "described below.", "

tbp/taf complex:", "complex: another", "another large", "large co", "a complex", "complex is", "the \\tbp", "\\tbp associated", "associated factors\\", "on tbp", "tata binding", "binding protein", "bound to", "box present", "many promoters.", "least 23", "23 human", "human taf", "taf proteins", "proteins that", "that have", "have been", "been identified.", "many of", "these are", "are ubiquitously", "but tafs", "tafs can", "can also", "also be", "be expressed", "expressed in", "

\tspecific", "\tspecific coactivator", "coactivator complexes", "complexes for", "for dna", "binding transcription", "transcription factors.", "

a number", "transcription factors", "factors have", "been identified", "including drip", "in bourbon", "and malik", "2005 .", "drip co", "activator complex", "complex was", "was originally", "originally identified", "identified and", "and named", "named as", "as a", "specific complex", "complex associated", "associated with", "with the", "the vitamin", "vitamin d", "d receptor", "receptor member", "member of", "the nuclear", "nuclear receptor", "receptor family", "family of", "1998 .", "the trap", "trap co", "identified as", "that associates", "associates with", "the thyroid", "thyroid receptor", "it was", "was later", "later determined", "determined that", "that all", "all of", "the components", "drip complex", "complex are", "also present", "trap complex", "and the", "the arc", "arc complex", "discussed further", "further below", "below .", "for example", "the drip205", "drip205 and", "and trap220", "trap220 proteins", "proteins were", "were show", "show to", "be identical", "as were", "were specific", "specific pairs", "pairs of", "the other", "other components", "these complexes", "1999 .

in", ".

in addition", "these various", "various transcription", "proteins identified", "identified in", "in mammalian", "mammalian cells", "cells were", "were found", "be the", "the orthologues", "orthologues or", "or homologues", "homologues of", "complex proteins", "2004 .", "mediator proteins", "were originally", "in yeast", "by kornberg", "kornberg and", "and colleagues", "as complexes", "complexes associated", "with dna", "1990 .", "higher organisms", "adapter complexes", "complexes bridge", "bridge between", "the basal", "basal transcription", "including pol", "and tissue", "to sites", "within upstream", "upstream proximal", "promoter regions", "regions or", "1 .", "mediator homologues", "homologues can", "be found", "found in", "in complexes", "with specific", "factors in", "higher organisms.", "a unified", "unified nomenclature", "nomenclature system", "system for", "for these", "these adapter", "adapter /", "/ co", "proteins now", "now labels", "labels them", "them mediator", "mediator 1", "1 through", "through mediator", "mediator 31", "drip205 /", "/ trap220", "are now", "now identified", "as mediator", "based on", "on homology", "homology with", "with yeast", "yeast mediator", "mediator 1.

", "1.

example", "example pathway:", "pathway: specific", "of target", "genes during", "during notch", "notch signaling:", "signaling:

one", "

one well", "well studied", "studied example", "example of", "of cell", "is selective", "selective regulation", "notch signaling.", "notch signaling", "signaling was", "was first", "first identified", "in drosophila", "where it", "it has", "been studied", "studied in", "in detail", "detail at", "at the", "the genetic", "biochemical and", "and cellular", "cellular levels", "in justice", "signaling to", "the nucleus", "nucleus is", "is thought", "thought always", "always to", "be mediated", "mediated by", "by one", "one specific", "transcription factor", "suppressor of", "of hairless.", "in mammals", "the homologous", "homologous genes", "genes are", "are called", "called cbf1", "or rbpjkappa", "while in", "in worms", "worms they", "they are", "called lag", "lag 1", "the acronym", "acronym \\csl\\", "\\csl\\ has", "been given", "given to", "to this", "this conserved", "conserved transcription", "factor family.", "two human", "human csl", "csl homologues", "now named", "named rbpj", "rbpj and", "and rbpjl.", "

in drosophila", "su h", "is known", "known to", "be bifunctional", "in that", "that it", "it represses", "represses target", "transcription in", "the absence", "absence of", "of notch", "but activates", "activates target", "some of", "the mammalian", "mammalian csl", "homologues are", "are believed", "believed also", "also to", "and to", "to mediate", "mediate target", "gene repression", "repression in", "and activation", "activation in", "notch signaling.

notch", "signaling.

notch co", "complexes: this", "this repression", "repression is", "by at", "least one", "to csl", "csl in", "this co", "repressor complex", "complex consists", "consists of", "of at", "least three", "three distinct", "distinct co", "repressor proteins:", "proteins: hairless", "and dctbp", "drosophila c", "c terminal", "terminal binding", "protein .", "hairless has", "been show", "to bind", "bind directly", "directly to", "to su", "and groucho", "groucho and", "dctbp have", "to hairless", "2002 .", "all three", "three of", "repressor proteins", "proteins have", "be necessary", "necessary for", "proper gene", "gene regulation", "regulation during", "signaling in", "in vivo", "2005 .

in", ".

in mammals", "the same", "same general", "general pathway", "pathway and", "mechanisms are", "are observed", "where csl", "csl proteins", "are bifunctional", "bifunctional dna", "that bind", "to co", "complexes to", "mediate repression", "and bind", "mediate activation", "there may", "may be", "be multiple", "multiple co", "than the", "the single", "single hairless", "hairless co", "been observed", "observed in", "in drosophila.", "

during notch", "in all", "all systems", "the notch", "notch transmembrane", "transmembrane receptor", "receptor is", "is cleaved", "cleaved and", "notch intracellular", "intracellular domain", "translocates to", "it there", "there functions", "activator for", "for csl", "csl proteins.", "nicd replaces", "replaces the", "r complex", "complex bound", "thus resulting", "resulting in", "in de", "de repression", "notch target", "figure 2", "2 .", "once bound", "nicd and", "and csl", "proteins recruit", "recruit an", "an additional", "additional co", "activator protein", "to form", "form a", "a csl", "csl nicd", "nicd mam", "mam ternary", "ternary co", "was initially", "initially thought", "thought to", "be sufficient", "sufficient to", "some notch", "target genes.", "there now", "now is", "is evidence", "evidence that", "that still", "still other", "other co", "co activators", "activators and", "and additional", "additional dna", "are required", "required in", "some contexts", "in barolo", "csl is", "a good", "good example", "of a", "a bifunctional", "factor that", "mediates repression", "specific targets", "targets genes", "in one", "one context", "but activation", "same targets", "targets in", "in another", "another context.", "this bifunctionality", "bifunctionality is", "the association", "association of", "complexes vs.", "vs. specific", "complexes in", "in different", "different contexts", "namely in", "absence or", "or presence", "overview of transcription", "of transcription regulation:", "regulation:

detailed", "

detailed studies of", "studies of gene", "of gene transcription", "gene transcription regulation", "transcription regulation in", "regulation in a", "in a wide", "a wide variety", "wide variety of", "variety of eukaryotic", "of eukaryotic systems", "eukaryotic systems has", "systems has revealed", "has revealed the", "revealed the general", "the general principles", "general principles and", "principles and mechanisms", "and mechanisms by", "mechanisms by which", "by which cell", "or tissue specific", "tissue specific regulation", "specific regulation of", "regulation of differential", "of differential gene", "differential gene transcription", "gene transcription is", "transcription is mediated", "mediated reviewed", "reviewed in naar", "naar 2001.", "kadonaga 2004", "2004 maston", "maston 2006", "2006 barolo", "barolo 2002", "2002 roeder", "roeder 2005", "2005 rosenfeld", "rosenfeld 2006", ". of", "of the three", "the three major", "three major classes", "major classes of", "classes of dna", "of dna polymerase", "dna polymerase involved", "polymerase involved in", "involved in eukaryotic", "in eukaryotic gene", "eukaryotic gene transcription", "transcription polymerase", "polymerase ii generally", "ii generally regulates", "generally regulates protein", "regulates protein encoding", "protein encoding genes.", "figure 1 shows", "1 shows a", "shows a diagram", "a diagram of", "diagram of the", "of the various", "the various components", "various components involved", "components involved in", "involved in cell", "in cell specific", "cell specific regulation", "regulation of pol", "of pol ii", "pol ii gene", "ii gene transcription.", "gene transcription.

core", "transcription.

core promoter:", "

core promoter: pol", "promoter: pol ii", "pol ii regulated", "ii regulated genes", "regulated genes typically", "genes typically have", "typically have a", "have a core", "a core promoter", "core promoter where", "promoter where pol", "where pol ii", "pol ii and", "ii and a", "and a variety", "a variety of", "variety of general", "of general factors", "general factors bind", "factors bind to", "bind to specific", "to specific dna", "specific dna motifs:", "dna motifs:
", "i: the tata", "the tata box", "box tata", "tata dna sequence", "which is bound", "is bound by", "bound by the", "by the \\tata", "the \\tata binding", "\\tata binding protein\\", "protein\\ tbp", "ii: the initiator", "the initiator motif", "motif inr", "ii and certain", "and certain other", "certain other core", "other core factors", "core factors bind", "bind is", "is present in", "present in many", "in many pol", "many pol ii", "ii regulated genes.
", "iii: the downstream", "the downstream promoter", "downstream promoter element", "element dpe", "which is present", "present in a", "in a subset", "a subset of", "subset of pol", "pol ii genes", "genes and", "and where additional", "where additional core", "additional core factors", "core factors bind.", "bind.
the", "
the core promoter", "core promoter binding", "promoter binding factors", "binding factors are", "factors are generally", "are generally ubiquitously", "generally ubiquitously expressed", "expressed although", "although there are", "there are exceptions", "are exceptions to", "exceptions to this.

proximal", "to this.

proximal promoter:", "this.

proximal promoter: immediately", "promoter: immediately upstream", "upstream 5'", "5' of", "of the core", "the core promoter", "promoter pol", "pol ii target", "ii target genes", "target genes often", "genes often have", "often have a", "have a proximal", "a proximal promoter", "proximal promoter region", "promoter region that", "region that spans", "that spans up", "spans up to", "up to 500", "to 500 base", "500 base pairs", "pairs b.p.", "or even to", "even to 1000", "to 1000 b.p..", "b.p.. this", "this region contains", "region contains a", "contains a number", "a number of", "number of functional", "of functional dna", "functional dna binding", "dna binding sites", "binding sites for", "sites for a", "for a specific", "a specific set", "specific set of", "set of transcription", "of transcription activator", "activator ta", "and transcription repressor", "repressor tr", "tr proteins.", "proteins. these", "these ta and", "ta and tr", "and tr factors", "tr factors are", "are generally cell", "tissue specific in", "specific in expression", "expression rather", "rather than ubiquitous", "ubiquitous so", "so that the", "that the presence", "the presence of", "presence of their", "of their cognate", "their cognate binding", "cognate binding sites", "binding sites in", "sites in the", "in the proximal", "the proximal promoter", "promoter region programs", "region programs cell", "tissue specific expression", "specific expression of", "expression of the", "of the target", "the target gene", "gene perhaps", "perhaps in conjunction", "in conjunction with", "conjunction with ta", "with ta and", "and tr complexes", "tr complexes bound", "complexes bound in", "bound in distal", "in distal enhancer", "distal enhancer regions.", "regions.

distal", "

distal enhancer s", "enhancer s :", "s : many", ": many or", "many or most", "or most pol", "most pol ii", "regulated genes in", "genes in higher", "in higher eukaryotes", "higher eukaryotes have", "eukaryotes have one", "have one or", "one or more", "or more distal", "more distal enhancer", "distal enhancer regions", "enhancer regions which", "regions which are", "which are essential", "are essential for", "essential for proper", "for proper regulation", "proper regulation of", "regulation of the", "of the gene", "gene often", "often in a", "in a cell", "a cell or", "cell or tissue", "tissue specific pattern.", "pattern. like", "like the proximal", "region each", "each of the", "of the distal", "the distal enhancer", "enhancer regions typically", "regions typically contain", "typically contain a", "contain a cluster", "a cluster of", "cluster of binding", "of binding sites", "sites for specific", "for specific ta", "specific ta and/or", "ta and/or tr", "and/or tr dna", "tr dna binding", "dna binding factors", "factors rather", "rather than just", "than just a", "just a single", "a single site.", "single site.

", "enhancers generally have", "generally have three", "have three defining", "three defining characteristics:
", "i: they can", "they can be", "can be located", "be located very", "located very long", "very long distances", "long distances from", "distances from the", "from the promoter", "the promoter of", "promoter of the", "target gene they", "gene they regulate", "regulate sometimes", "sometimes as far", "as far as", "far as 100", "as 100 kb", "kb or", "ii: they can", "can be either", "be either upstream", "5' or", "downstream 3'", "3' of", "gene including", "including within introns", "within introns of", "introns of that", "of that gene.
", "iii: they can", "they can function", "can function in", "function in either", "in either orientation", "either orientation in", "orientation in the", "in the dna.

combinatorial", "the dna.

combinatorial mechanisms", "dna.

combinatorial mechanisms of", "mechanisms of transcription", "of transcription regulation:", "transcription regulation: the", "regulation: the specific", "the specific combination", "specific combination of", "combination of ta", "of ta and", "and tr binding", "tr binding sites", "binding sites within", "sites within the", "within the proximal", "proximal promoter and/or", "promoter and/or distal", "and/or distal enhancer", "distal enhancer s", "s provides", "provides a \\combinatorial", "a \\combinatorial transcription", "\\combinatorial transcription code\\", "transcription code\\ that", "code\\ that mediates", "that mediates cell", "of the associated", "the associated target", "associated target gene.", "gene. each", "each promoter or", "promoter or enhancer", "or enhancer region", "enhancer region mediates", "region mediates expression", "mediates expression in", "expression in a", "in a specific", "a specific subset", "specific subset of", "subset of the", "of the overall", "the overall expression", "overall expression pattern.", "pattern. in", "in at least", "at least some", "least some cases", "cases each", "each enhancer region", "enhancer region functions", "region functions completely", "functions completely independently", "completely independently of", "independently of the", "of the others", "others so", "that the overall", "overall expression pattern", "expression pattern is", "pattern is a", "is a linear", "a linear combination", "linear combination of", "combination of the", "of the expression", "the expression patterns", "expression patterns of", "patterns of each", "of each of", "of the enhancer", "the enhancer modules.

co", "enhancer modules.

co activator", "modules.

co activator and", "activator and co", "and co repressor", "co repressor complexes:", "complexes: dna", "dna bound ta", "bound ta and", "and tr proteins", "tr proteins typically", "proteins typically recruit", "typically recruit the", "recruit the assembly", "the assembly of", "assembly of specific", "of specific co", "specific co activator", "activator co", "a and", "repressor co", "r complexes", "complexes respectively", "respectively which", "essential for regulating", "for regulating target", "regulating target gene", "target gene transcription.", "transcription. both", "both co a's", "co a's and", "a's and co", "and co r's", "r's are", "are multi protein", "multi protein complexes", "protein complexes that", "complexes that contain", "that contain several", "contain several specific", "several specific protein", "specific protein components.

co", "protein components.

co activator", "components.

co activator complexes", "activator complexes generally", "complexes generally contain", "generally contain at", "contain at lease", "at lease one", "lease one component", "one component protein", "component protein that", "protein that has", "that has histone", "has histone acetyl", "histone acetyl transferase", "transferase hat", "hat enzymatic", "activity. this", "this functions to", "functions to acetylate", "to acetylate histones", "acetylate histones and/or", "histones and/or other", "and/or other chromatin", "other chromatin associated", "chromatin associated factors", "factors which", "which typically increases", "typically increases that", "increases that transcription", "that transcription activation", "transcription activation of", "activation of the", "the target gene.", "gene. by", "contrast co", "co repressor complexes", "repressor complexes generally", "has histone de", "histone de acetylase", "acetylase hdac", "hdac enzymatic", "functions to de", "to de acetylate", "de acetylate histones", "chromatin associated factors.", "associated factors. this", "factors. this typically", "this typically increases", "typically increases the", "increases the transcription", "the transcription repression", "transcription repression of", "repression of the", "the target gene.

adaptor", "gene.

adaptor mediator", "mediator complexes:", "complexes: in addition", "in addition to", "addition to the", "to the co", "the co activator", "co activator complexes", "activator complexes that", "complexes that assemble", "that assemble on", "assemble on particular", "on particular cell", "particular cell specific", "cell specific ta", "specific ta factors", "there are at", "are at least", "at least two", "least two additional", "two additional transcriptional", "additional transcriptional co", "transcriptional co activator", "activator complexes common", "complexes common to", "common to most", "to most cells.", "cells. one", "one of these", "of these is", "these is the", "is the mediator", "the mediator complex", "complex which", "which functions as", "functions as an", "as an \\adaptor\\", "an \\adaptor\\ complex", "\\adaptor\\ complex that", "complex that bridges", "that bridges between", "bridges between the", "between the tissue", "the tissue specific", "tissue specific co", "activator complexes assembled", "complexes assembled in", "assembled in the", "or distal enhancers", "distal enhancers .", ". the", "the human mediator", "human mediator complex", "mediator complex has", "complex has been", "has been shown", "been shown to", "shown to contain", "to contain at", "contain at least", "at least 19", "least 19 protein", "19 protein distinct", "protein distinct components.", "components. different", "different combinations of", "combinations of these", "of these co", "these co activator", "co activator proteins", "activator proteins are", "proteins are also", "are also found", "also found to", "found to be", "to be components", "be components of", "components of specific", "of specific transcription", "specific transcription co", "transcription co activator", "complexes such", "such as the", "as the drip", "drip trap", "trap and arc", "and arc complexes", "arc complexes described", "complexes described below.", "below.

tbp/taf", "

tbp/taf complex: another", "complex: another large", "another large co", "large co a", "co a complex", "a complex is", "complex is the", "is the \\tbp", "the \\tbp associated", "\\tbp associated factors\\", "factors\\ tafs", "tafs that", "assemble on tbp", "tbp tata", "tata binding protein", "is bound to", "bound to the", "to the tata", "tata box present", "box present in", "in many promoters.", "promoters. there", "at least 23", "least 23 human", "23 human taf", "human taf proteins", "taf proteins that", "proteins that have", "that have been", "have been identified.", "identified. many", "many of these", "of these are", "these are ubiquitously", "are ubiquitously expressed", "expressed but", "but tafs can", "tafs can also", "can also be", "also be expressed", "be expressed in", "expressed in a", "pattern.

", "

\tspecific coactivator", "\tspecific coactivator complexes", "coactivator complexes for", "complexes for dna", "for dna binding", "dna binding transcription", "binding transcription factors.", "

a number of", "number of specific", "activator complexes for", "binding transcription factors", "transcription factors have", "factors have been", "have been identified", "identified including", "arc reviewed", "reviewed in bourbon", "bourbon 2004", "2004 blazek", "blazek 2005", "2005 conaway", "conaway 2005", "2005 and", "malik 2005", "the drip co", "drip co activator", "co activator complex", "activator complex was", "complex was originally", "was originally identified", "originally identified and", "identified and named", "and named as", "named as a", "as a specific", "a specific complex", "specific complex associated", "complex associated with", "associated with the", "with the vitamin", "the vitamin d", "vitamin d receptor", "d receptor member", "receptor member of", "member of the", "of the nuclear", "the nuclear receptor", "nuclear receptor family", "receptor family of", "family of transcription", "of transcription factors", "factors rachez", "rachez 1998", ". similarly", "similarly the", "the trap co", "trap co activator", "originally identified as", "identified as a", "as a complex", "a complex that", "complex that associates", "that associates with", "associates with the", "with the thyroid", "the thyroid receptor", "receptor yuan", "yuan 1998", "it was later", "was later determined", "later determined that", "determined that all", "that all of", "all of the", "of the components", "the components of", "components of the", "of the drip", "the drip complex", "drip complex are", "complex are also", "are also present", "also present in", "present in the", "in the trap", "the trap complex", "complex and", "and the arc", "the arc complex", "complex discussed", "discussed further below", "further below .", ". for", "example the", "the drip205 and", "drip205 and trap220", "and trap220 proteins", "trap220 proteins were", "proteins were show", "were show to", "show to be", "to be identical", "identical as", "as were specific", "were specific pairs", "specific pairs of", "pairs of the", "of the other", "the other components", "other components of", "components of these", "of these complexes", "complexes rachez", "rachez 1999", "1999 .

in addition", "addition these", "these various transcription", "various transcription co", "activator proteins identified", "proteins identified in", "identified in mammalian", "in mammalian cells", "mammalian cells were", "cells were found", "were found to", "to be the", "be the orthologues", "the orthologues or", "orthologues or homologues", "or homologues of", "homologues of the", "of the mediator", "mediator \\adaptor\\", "proteins reviewed", "the mediator proteins", "mediator proteins were", "proteins were originally", "were originally identified", "originally identified in", "identified in yeast", "yeast by", "by kornberg and", "kornberg and colleagues", "colleagues as", "as complexes associated", "complexes associated with", "associated with dna", "with dna polymerase", "polymerase kelleher", "kelleher 1990", ". in", "in higher organisms", "organisms adapter", "adapter complexes bridge", "complexes bridge between", "bridge between the", "between the basal", "the basal transcription", "basal transcription factors", "factors including", "including pol ii", "and tissue specific", "tissue specific transcription", "specific transcription factors", "factors tfs", "tfs bound", "bound to sites", "to sites within", "sites within upstream", "within upstream proximal", "upstream proximal promoter", "proximal promoter regions", "promoter regions or", "regions or distal", "or distal enhancer", "regions figure", "figure 1 .", ". however", "however many", "many of the", "the mediator homologues", "mediator homologues can", "homologues can also", "also be found", "be found in", "found in complexes", "in complexes associated", "associated with specific", "with specific transcription", "transcription factors in", "factors in higher", "in higher organisms.", "organisms. a", "a unified nomenclature", "unified nomenclature system", "nomenclature system for", "system for these", "for these adapter", "these adapter /", "adapter / co", "/ co activator", "activator proteins now", "proteins now labels", "now labels them", "labels them mediator", "them mediator 1", "mediator 1 through", "1 through mediator", "through mediator 31", "31 bourbon", "the drip205 /", "drip205 / trap220", "/ trap220 proteins", "trap220 proteins are", "proteins are now", "are now identified", "now identified as", "identified as mediator", "as mediator 1", "1 rachez", "based on homology", "on homology with", "homology with yeast", "with yeast mediator", "yeast mediator 1.

", "mediator 1.

example", "1.

example pathway:", "example pathway: specific", "pathway: specific regulation", "regulation of target", "of target genes", "target genes during", "genes during notch", "during notch signaling:", "notch signaling:

one", "signaling:

one well", "

one well studied", "well studied example", "studied example of", "example of cell", "of cell specific", "regulation of gene", "transcription is selective", "is selective regulation", "selective regulation of", "during notch signaling.", "signaling. notch", "notch signaling was", "signaling was first", "was first identified", "first identified in", "identified in drosophila", "drosophila where", "where it has", "it has been", "has been studied", "been studied in", "studied in detail", "in detail at", "detail at the", "at the genetic", "genetic molecular", "molecular biochemical", "biochemical and cellular", "and cellular levels", "levels reviewed", "reviewed in justice", "justice 2002", "2002 bray", "bray 2006", "2006 schweisguth", "schweisguth 2004", "2004 louvri", "louvri 2006", "drosophila notch", "notch signaling to", "signaling to the", "to the nucleus", "the nucleus is", "nucleus is thought", "is thought always", "thought always to", "always to be", "to be mediated", "be mediated by", "mediated by one", "by one specific", "one specific dna", "specific dna binding", "binding transcription factor", "factor suppressor", "suppressor of hairless.", "hairless. in", "mammals the", "the homologous genes", "homologous genes are", "genes are called", "are called cbf1", "cbf1 or", "while in worms", "in worms they", "worms they are", "they are called", "are called lag", "called lag 1", "1 so", "that the acronym", "the acronym \\csl\\", "acronym \\csl\\ has", "\\csl\\ has been", "has been given", "been given to", "given to this", "to this conserved", "this conserved transcription", "conserved transcription factor", "transcription factor family.", "family. there", "least two human", "two human csl", "human csl homologues", "homologues which", "which are now", "are now named", "now named rbpj", "named rbpj and", "rbpj and rbpjl.", "rbpjl.

in", "drosophila su", "h is", "is known to", "known to be", "to be bifunctional", "bifunctional in", "in that it", "that it represses", "it represses target", "represses target gene", "target gene transcription", "gene transcription in", "transcription in the", "in the absence", "the absence of", "absence of notch", "of notch signaling", "signaling but", "but activates target", "activates target genes", "signaling. at", "least some of", "some of the", "of the mammalian", "the mammalian csl", "mammalian csl homologues", "csl homologues are", "homologues are believed", "are believed also", "believed also to", "also to be", "bifunctional and", "and to mediate", "to mediate target", "mediate target gene", "target gene repression", "gene repression in", "repression in the", "signaling and", "and activation in", "activation in the", "in the presence", "presence of notch", "of notch signaling.

notch", "notch signaling.

notch co", "signaling.

notch co activator", "co activator and", "repressor complexes: this", "complexes: this repression", "this repression is", "repression is mediated", "is mediated by", "mediated by at", "by at least", "at least one", "least one specific", "one specific co", "specific co repressor", "complexes co", "r bound", "bound to csl", "to csl in", "csl in the", "of notch signaling.", "signaling. in", "drosophila this", "this co repressor", "co repressor complex", "repressor complex consists", "complex consists of", "consists of at", "of at least", "at least three", "least three distinct", "three distinct co", "distinct co repressor", "co repressor proteins:", "repressor proteins: hairless", "hairless groucho", "dctbp drosophila", "drosophila c terminal", "c terminal binding", "terminal binding protein", "binding protein .", ". hairless", "hairless has been", "has been show", "been show to", "show to bind", "to bind directly", "bind directly to", "directly to su", "to su h", "and groucho and", "groucho and dctbp", "and dctbp have", "dctbp have been", "have been shown", "shown to bind", "directly to hairless", "hairless barolo", ". all", "all three of", "three of the", "of the co", "the co repressor", "co repressor proteins", "repressor proteins have", "proteins have been", "shown to be", "to be necessary", "be necessary for", "necessary for proper", "for proper gene", "proper gene regulation", "gene regulation during", "regulation during notch", "during notch signaling", "notch signaling in", "signaling in vivo", "vivo nagel", "nagel 2005", "2005 .

in mammals", "the same general", "same general pathway", "general pathway and", "pathway and mechanisms", "and mechanisms are", "mechanisms are observed", "observed where", "where csl proteins", "csl proteins are", "proteins are bifunctional", "are bifunctional dna", "bifunctional dna binding", "that bind to", "bind to co", "to co repressor", "repressor complexes to", "complexes to mediate", "to mediate repression", "mediate repression in", "and bind to", "to co activator", "to mediate activation", "mediate activation in", "signaling. however", "however in", "mammals there", "there may be", "may be multiple", "be multiple co", "multiple co repressor", "complexes rather", "rather than the", "than the single", "the single hairless", "single hairless co", "hairless co repressor", "repressor complex that", "complex that has", "that has been", "has been observed", "been observed in", "observed in drosophila.", "drosophila.

during", "

during notch signaling", "signaling in all", "in all systems", "systems the", "the notch transmembrane", "notch transmembrane receptor", "transmembrane receptor is", "receptor is cleaved", "is cleaved and", "cleaved and the", "and the notch", "the notch intracellular", "notch intracellular domain", "domain nicd", "nicd translocates", "translocates to the", "nucleus where", "where it there", "it there functions", "there functions as", "functions as a", "a specific transcription", "co activator for", "activator for csl", "for csl proteins.", "proteins. in", "in the nucleus", "nucleus nicd", "nicd replaces the", "replaces the co", "the co r", "co r complex", "r complex bound", "complex bound to", "csl thus", "thus resulting in", "resulting in de", "in de repression", "de repression of", "notch target genes", "target genes in", "genes in the", "nucleus figure", "figure 2 .", ". once", "once bound to", "nicd and csl", "and csl proteins", "csl proteins recruit", "proteins recruit an", "recruit an additional", "an additional co", "additional co activator", "co activator protein", "protein mastermind", "mastermind to", "to form a", "form a csl", "a csl nicd", "csl nicd mam", "nicd mam ternary", "mam ternary co", "ternary co activator", "a complex.", "complex. this", "this co r", "complex was initially", "was initially thought", "initially thought to", "thought to be", "to be sufficient", "be sufficient to", "sufficient to mediate", "mediate activation of", "least some notch", "some notch target", "notch target genes.", "genes. however", "however there", "there now is", "now is evidence", "is evidence that", "evidence that still", "that still other", "still other co", "other co activators", "co activators and", "activators and additional", "and additional dna", "additional dna binding", "transcription factors are", "factors are required", "are required in", "required in at", "least some contexts", "contexts reviewed", "reviewed in barolo", ".

thus", "

thus csl", "csl is a", "is a good", "a good example", "good example of", "example of a", "of a bifunctional", "a bifunctional dna", "transcription factor that", "factor that mediates", "that mediates repression", "mediates repression of", "repression of specific", "of specific targets", "specific targets genes", "targets genes in", "genes in one", "in one context", "context but", "but activation of", "of the same", "the same targets", "same targets in", "targets in another", "in another context.", "context. this", "this bifunctionality is", "bifunctionality is mediated", "mediated by the", "by the association", "the association of", "association of specific", "repressor complexes vs.", "complexes vs. specific", "vs. specific co", "activator complexes in", "complexes in different", "in different contexts", "contexts namely", "namely in the", "the absence or", "absence or presence", "or presence of", "overview of transcription regulation:", "transcription regulation:

detailed", "regulation:

detailed studies", "

detailed studies of gene", "studies of gene transcription", "of gene transcription regulation", "gene transcription regulation in", "transcription regulation in a", "regulation in a wide", "in a wide variety", "a wide variety of", "wide variety of eukaryotic", "variety of eukaryotic systems", "of eukaryotic systems has", "eukaryotic systems has revealed", "systems has revealed the", "has revealed the general", "revealed the general principles", "the general principles and", "general principles and mechanisms", "principles and mechanisms by", "and mechanisms by which", "mechanisms by which cell", "which cell or", "or tissue specific regulation", "tissue specific regulation of", "specific regulation of differential", "regulation of differential gene", "of differential gene transcription", "differential gene transcription is", "gene transcription is mediated", "is mediated reviewed", "mediated reviewed in", "in naar 2001.", "naar 2001. kadonaga", "2001. kadonaga 2004", "rosenfeld 2006 .", "2006 . of", ". of the", "of the three major", "the three major classes", "three major classes of", "major classes of dna", "classes of dna polymerase", "of dna polymerase involved", "dna polymerase involved in", "polymerase involved in eukaryotic", "involved in eukaryotic gene", "in eukaryotic gene transcription", "gene transcription polymerase", "transcription polymerase ii", "polymerase ii generally regulates", "ii generally regulates protein", "generally regulates protein encoding", "regulates protein encoding genes.", "genes. figure", "figure 1 shows a", "1 shows a diagram", "shows a diagram of", "a diagram of the", "diagram of the various", "of the various components", "the various components involved", "various components involved in", "components involved in cell", "involved in cell specific", "in cell specific regulation", "cell specific regulation of", "specific regulation of pol", "regulation of pol ii", "of pol ii gene", "pol ii gene transcription.", "ii gene transcription.

core", "gene transcription.

core promoter:", "transcription.

core promoter: pol", "

core promoter: pol ii", "promoter: pol ii regulated", "pol ii regulated genes", "ii regulated genes typically", "regulated genes typically have", "genes typically have a", "typically have a core", "have a core promoter", "a core promoter where", "core promoter where pol", "promoter where pol ii", "where pol ii and", "pol ii and a", "ii and a variety", "and a variety of", "a variety of general", "variety of general factors", "of general factors bind", "general factors bind to", "factors bind to specific", "bind to specific dna", "to specific dna motifs:", "specific dna motifs:
", "
i:", "i: the tata box", "tata box tata", "box tata dna", "sequence which", "which is bound by", "is bound by the", "bound by the \\tata", "by the \\tata binding", "the \\tata binding protein\\", "binding protein\\ tbp", "protein\\ tbp .
", ".
ii:", "ii: the initiator motif", "initiator motif inr", "inr where", "pol ii and certain", "ii and certain other", "and certain other core", "certain other core factors", "other core factors bind", "factors bind is", "bind is present", "is present in many", "present in many pol", "in many pol ii", "many pol ii regulated", "pol ii regulated genes.
", "genes.
iii:", "iii: the downstream promoter", "the downstream promoter element", "promoter element dpe", "dpe which", "which is present in", "is present in a", "present in a subset", "in a subset of", "a subset of pol", "subset of pol ii", "of pol ii genes", "ii genes and", "genes and where", "and where additional core", "where additional core factors", "additional core factors bind.", "factors bind.
the", "bind.
the core", "
the core promoter binding", "core promoter binding factors", "promoter binding factors are", "binding factors are generally", "factors are generally ubiquitously", "are generally ubiquitously expressed", "ubiquitously expressed although", "expressed although there", "although there are exceptions", "there are exceptions to", "are exceptions to this.

proximal", "exceptions to this.

proximal promoter:", "to this.

proximal promoter: immediately", "this.

proximal promoter: immediately upstream", "immediately upstream 5'", "5' of the", "of the core promoter", "core promoter pol", "promoter pol ii", "pol ii target genes", "ii target genes often", "target genes often have", "genes often have a", "often have a proximal", "have a proximal promoter", "a proximal promoter region", "proximal promoter region that", "promoter region that spans", "region that spans up", "that spans up to", "spans up to 500", "up to 500 base", "to 500 base pairs", "base pairs b.p.", "b.p. or", "or even to 1000", "even to 1000 b.p..", "1000 b.p.. this", "b.p.. this region", "this region contains a", "region contains a number", "contains a number of", "a number of functional", "number of functional dna", "of functional dna binding", "functional dna binding sites", "dna binding sites for", "binding sites for a", "sites for a specific", "for a specific set", "a specific set of", "specific set of transcription", "set of transcription activator", "transcription activator ta", "ta and transcription", "transcription repressor tr", "proteins. these ta", "these ta and tr", "ta and tr factors", "and tr factors are", "tr factors are generally", "factors are generally cell", "generally cell or", "or tissue specific in", "tissue specific in expression", "in expression rather", "expression rather than", "than ubiquitous so", "ubiquitous so that", "so that the presence", "that the presence of", "the presence of their", "presence of their cognate", "of their cognate binding", "their cognate binding sites", "cognate binding sites in", "binding sites in the", "sites in the proximal", "in the proximal promoter", "the proximal promoter region", "proximal promoter region programs", "promoter region programs cell", "programs cell or", "or tissue specific expression", "tissue specific expression of", "specific expression of the", "expression of the target", "of the target gene", "target gene perhaps", "gene perhaps in", "perhaps in conjunction with", "in conjunction with ta", "conjunction with ta and", "with ta and tr", "ta and tr complexes", "and tr complexes bound", "tr complexes bound in", "complexes bound in distal", "bound in distal enhancer", "in distal enhancer regions.", "enhancer regions.

distal", "regions.

distal enhancer", "

distal enhancer s :", "enhancer s : many", "s : many or", ": many or most", "many or most pol", "or most pol ii", "most pol ii regulated", "ii regulated genes in", "regulated genes in higher", "genes in higher eukaryotes", "in higher eukaryotes have", "higher eukaryotes have one", "eukaryotes have one or", "have one or more", "one or more distal", "or more distal enhancer", "more distal enhancer regions", "distal enhancer regions which", "enhancer regions which are", "regions which are essential", "which are essential for", "are essential for proper", "essential for proper regulation", "for proper regulation of", "proper regulation of the", "regulation of the gene", "the gene often", "gene often in", "often in a cell", "in a cell or", "a cell or tissue", "cell or tissue specific", "or tissue specific pattern.", "specific pattern. like", "pattern. like the", "like the proximal promoter", "promoter region each", "region each of", "each of the distal", "of the distal enhancer", "the distal enhancer regions", "distal enhancer regions typically", "enhancer regions typically contain", "regions typically contain a", "typically contain a cluster", "contain a cluster of", "a cluster of binding", "cluster of binding sites", "of binding sites for", "binding sites for specific", "sites for specific ta", "for specific ta and/or", "specific ta and/or tr", "ta and/or tr dna", "and/or tr dna binding", "tr dna binding factors", "binding factors rather", "factors rather than", "rather than just a", "than just a single", "just a single site.", "a single site.

", "

enhancers", "enhancers generally have three", "generally have three defining", "have three defining characteristics:
", "i: they can be", "they can be located", "can be located very", "be located very long", "located very long distances", "very long distances from", "long distances from the", "distances from the promoter", "from the promoter of", "the promoter of the", "promoter of the target", "the target gene they", "target gene they regulate", "they regulate sometimes", "regulate sometimes as", "sometimes as far as", "as far as 100", "far as 100 kb", "100 kb or", "kb or more.
", "ii: they can be", "they can be either", "can be either upstream", "either upstream 5'", "5' or downstream", "or downstream 3'", "3' of the", "target gene including", "gene including within", "including within introns of", "within introns of that", "introns of that gene.
", "iii: they can function", "they can function in", "can function in either", "function in either orientation", "in either orientation in", "either orientation in the", "orientation in the dna.

combinatorial", "in the dna.

combinatorial mechanisms", "the dna.

combinatorial mechanisms of", "dna.

combinatorial mechanisms of transcription", "mechanisms of transcription regulation:", "of transcription regulation: the", "transcription regulation: the specific", "regulation: the specific combination", "the specific combination of", "specific combination of ta", "combination of ta and", "of ta and tr", "ta and tr binding", "and tr binding sites", "tr binding sites within", "binding sites within the", "sites within the proximal", "within the proximal promoter", "the proximal promoter and/or", "proximal promoter and/or distal", "promoter and/or distal enhancer", "and/or distal enhancer s", "enhancer s provides", "s provides a", "provides a \\combinatorial transcription", "a \\combinatorial transcription code\\", "\\combinatorial transcription code\\ that", "transcription code\\ that mediates", "code\\ that mediates cell", "mediates cell or", "expression of the associated", "of the associated target", "the associated target gene.", "target gene. each", "gene. each promoter", "each promoter or enhancer", "promoter or enhancer region", "or enhancer region mediates", "enhancer region mediates expression", "region mediates expression in", "mediates expression in a", "expression in a specific", "in a specific subset", "a specific subset of", "specific subset of the", "subset of the overall", "of the overall expression", "the overall expression pattern.", "expression pattern. in", "pattern. in at", "in at least some", "at least some cases", "some cases each", "cases each enhancer", "each enhancer region functions", "enhancer region functions completely", "region functions completely independently", "functions completely independently of", "completely independently of the", "independently of the others", "the others so", "others so that", "so that the overall", "that the overall expression", "the overall expression pattern", "overall expression pattern is", "expression pattern is a", "pattern is a linear", "is a linear combination", "a linear combination of", "linear combination of the", "combination of the expression", "of the expression patterns", "the expression patterns of", "expression patterns of each", "patterns of each of", "of each of the", "each of the enhancer", "of the enhancer modules.

co", "the enhancer modules.

co activator", "enhancer modules.

co activator and", "modules.

co activator and co", "activator and co repressor", "and co repressor complexes:", "repressor complexes: dna", "complexes: dna bound", "dna bound ta and", "bound ta and tr", "ta and tr proteins", "and tr proteins typically", "tr proteins typically recruit", "proteins typically recruit the", "typically recruit the assembly", "recruit the assembly of", "the assembly of specific", "assembly of specific co", "of specific co activator", "co activator co", "activator co a", "co a and", "a and co", "co repressor co", "repressor co r", "co r complexes", "respectively which are", "are essential for regulating", "essential for regulating target", "for regulating target gene", "regulating target gene transcription.", "gene transcription. both", "transcription. both co", "both co a's and", "co a's and co", "a's and co r's", "co r's are", "r's are multi", "are multi protein complexes", "multi protein complexes that", "protein complexes that contain", "complexes that contain several", "that contain several specific", "contain several specific protein", "several specific protein components.

co", "specific protein components.

co activator", "protein components.

co activator complexes", "components.

co activator complexes generally", "activator complexes generally contain", "complexes generally contain at", "generally contain at lease", "contain at lease one", "at lease one component", "lease one component protein", "one component protein that", "component protein that has", "protein that has histone", "that has histone acetyl", "has histone acetyl transferase", "acetyl transferase hat", "hat enzymatic activity.", "enzymatic activity. this", "activity. this functions", "this functions to acetylate", "functions to acetylate histones", "to acetylate histones and/or", "acetylate histones and/or other", "histones and/or other chromatin", "and/or other chromatin associated", "other chromatin associated factors", "associated factors which", "factors which typically", "which typically increases that", "typically increases that transcription", "increases that transcription activation", "that transcription activation of", "transcription activation of the", "activation of the target", "of the target gene.", "target gene. by", "gene. by contrast", "by contrast co", "contrast co repressor", "co repressor complexes generally", "repressor complexes generally contain", "that has histone de", "has histone de acetylase", "de acetylase hdac", "hdac enzymatic activity.", "this functions to de", "functions to de acetylate", "to de acetylate histones", "de acetylate histones and/or", "other chromatin associated factors.", "chromatin associated factors. this", "associated factors. this typically", "factors. this typically increases", "this typically increases the", "typically increases the transcription", "increases the transcription repression", "the transcription repression of", "transcription repression of the", "repression of the target", "of the target gene.

adaptor", "target gene.

adaptor mediator", "mediator complexes: in", "complexes: in addition to", "in addition to the", "addition to the co", "to the co activator", "the co activator complexes", "co activator complexes that", "activator complexes that assemble", "complexes that assemble on", "that assemble on particular", "assemble on particular cell", "on particular cell specific", "particular cell specific ta", "cell specific ta factors", "there are at least", "are at least two", "at least two additional", "least two additional transcriptional", "two additional transcriptional co", "additional transcriptional co activator", "transcriptional co activator complexes", "co activator complexes common", "activator complexes common to", "complexes common to most", "common to most cells.", "most cells. one", "cells. one of", "one of these is", "of these is the", "these is the mediator", "is the mediator complex", "mediator complex which", "complex which functions", "which functions as an", "functions as an \\adaptor\\", "as an \\adaptor\\ complex", "an \\adaptor\\ complex that", "\\adaptor\\ complex that bridges", "complex that bridges between", "that bridges between the", "bridges between the tissue", "between the tissue specific", "the tissue specific co", "tissue specific co activator", "specific co activator complexes", "co activator complexes assembled", "activator complexes assembled in", "complexes assembled in the", "assembled in the proximal", "proximal promoter or", "promoter or distal", "or distal enhancers .", "enhancers . the", ". the human", "the human mediator complex", "human mediator complex has", "mediator complex has been", "complex has been shown", "has been shown to", "been shown to contain", "shown to contain at", "to contain at least", "contain at least 19", "at least 19 protein", "least 19 protein distinct", "19 protein distinct components.", "distinct components. different", "components. different combinations", "different combinations of these", "combinations of these co", "of these co activator", "these co activator proteins", "co activator proteins are", "activator proteins are also", "proteins are also found", "are also found to", "also found to be", "found to be components", "to be components of", "be components of specific", "components of specific transcription", "of specific transcription co", "specific transcription co activator", "transcription co activator complexes", "activator complexes such", "complexes such as", "such as the drip", "the drip trap", "drip trap and", "trap and arc complexes", "and arc complexes described", "arc complexes described below.", "described below.

tbp/taf", "below.

tbp/taf complex:", "

tbp/taf complex: another large", "complex: another large co", "another large co a", "large co a complex", "co a complex is", "a complex is the", "complex is the \\tbp", "is the \\tbp associated", "the \\tbp associated factors\\", "associated factors\\ tafs", "tafs that assemble", "that assemble on tbp", "on tbp tata", "tbp tata binding", "protein which", "which is bound to", "is bound to the", "bound to the tata", "to the tata box", "the tata box present", "tata box present in", "box present in many", "present in many promoters.", "many promoters. there", "promoters. there are", "are at least 23", "at least 23 human", "least 23 human taf", "23 human taf proteins", "human taf proteins that", "taf proteins that have", "proteins that have been", "that have been identified.", "been identified. many", "identified. many of", "many of these are", "of these are ubiquitously", "these are ubiquitously expressed", "ubiquitously expressed but", "expressed but tafs", "but tafs can also", "tafs can also be", "can also be expressed", "also be expressed in", "be expressed in a", "expressed in a cell", "specific pattern.

", "pattern.

\tspecific", "

\tspecific coactivator complexes", "\tspecific coactivator complexes for", "coactivator complexes for dna", "complexes for dna binding", "for dna binding transcription", "dna binding transcription factors.", "factors.

a", "

a number of specific", "number of specific co", "co activator complexes for", "activator complexes for dna", "dna binding transcription factors", "binding transcription factors have", "transcription factors have been", "factors have been identified", "been identified including", "identified including drip", "including drip trap", "and arc reviewed", "arc reviewed in", "in bourbon 2004", "2005 and malik", "and malik 2005", "malik 2005 .", "2005 . the", ". the drip", "the drip co activator", "drip co activator complex", "co activator complex was", "activator complex was originally", "complex was originally identified", "was originally identified and", "originally identified and named", "identified and named as", "and named as a", "named as a specific", "as a specific complex", "a specific complex associated", "specific complex associated with", "complex associated with the", "associated with the vitamin", "with the vitamin d", "the vitamin d receptor", "vitamin d receptor member", "d receptor member of", "receptor member of the", "member of the nuclear", "of the nuclear receptor", "the nuclear receptor family", "nuclear receptor family of", "receptor family of transcription", "family of transcription factors", "transcription factors rachez", "rachez 1998 .", "1998 . similarly", "similarly the trap", "the trap co activator", "trap co activator complex", "was originally identified as", "originally identified as a", "identified as a complex", "as a complex that", "a complex that associates", "complex that associates with", "that associates with the", "associates with the thyroid", "with the thyroid receptor", "thyroid receptor yuan", "yuan 1998 .", ". it", "it was later determined", "was later determined that", "later determined that all", "determined that all of", "that all of the", "all of the components", "of the components of", "the components of the", "components of the drip", "of the drip complex", "the drip complex are", "drip complex are also", "complex are also present", "are also present in", "also present in the", "present in the trap", "in the trap complex", "trap complex and", "complex and the", "and the arc complex", "arc complex discussed", "complex discussed further", "discussed further below .", "below . for", ". for example", "for example the", "example the drip205", "the drip205 and trap220", "drip205 and trap220 proteins", "and trap220 proteins were", "trap220 proteins were show", "proteins were show to", "were show to be", "show to be identical", "be identical as", "identical as were", "as were specific pairs", "were specific pairs of", "specific pairs of the", "pairs of the other", "of the other components", "the other components of", "other components of these", "components of these complexes", "these complexes rachez", "rachez 1999 .

in", ".

in addition these", "addition these various", "these various transcription co", "various transcription co activator", "transcription co activator proteins", "co activator proteins identified", "activator proteins identified in", "proteins identified in mammalian", "identified in mammalian cells", "in mammalian cells were", "mammalian cells were found", "cells were found to", "were found to be", "found to be the", "to be the orthologues", "be the orthologues or", "the orthologues or homologues", "orthologues or homologues of", "or homologues of the", "homologues of the mediator", "the mediator \\adaptor\\", "\\adaptor\\ complex proteins", "complex proteins reviewed", "proteins reviewed in", "bourbon 2004 .", "2004 . the", ". the mediator", "the mediator proteins were", "mediator proteins were originally", "proteins were originally identified", "were originally identified in", "originally identified in yeast", "in yeast by", "yeast by kornberg", "by kornberg and colleagues", "and colleagues as", "colleagues as complexes", "as complexes associated with", "complexes associated with dna", "associated with dna polymerase", "dna polymerase kelleher", "kelleher 1990 .", "1990 . in", ". in higher", "higher organisms adapter", "organisms adapter complexes", "adapter complexes bridge between", "complexes bridge between the", "bridge between the basal", "between the basal transcription", "the basal transcription factors", "transcription factors including", "factors including pol", "ii and tissue", "and tissue specific transcription", "tissue specific transcription factors", "transcription factors tfs", "tfs bound to", "bound to sites within", "to sites within upstream", "sites within upstream proximal", "within upstream proximal promoter", "upstream proximal promoter regions", "proximal promoter regions or", "promoter regions or distal", "regions or distal enhancer", "or distal enhancer regions", "enhancer regions figure", "regions figure 1", "1 . however", "however many of", "many of the mediator", "of the mediator homologues", "the mediator homologues can", "mediator homologues can also", "homologues can also be", "can also be found", "also be found in", "be found in complexes", "found in complexes associated", "in complexes associated with", "complexes associated with specific", "associated with specific transcription", "with specific transcription factors", "specific transcription factors in", "transcription factors in higher", "factors in higher organisms.", "higher organisms. a", "organisms. a unified", "a unified nomenclature system", "unified nomenclature system for", "nomenclature system for these", "system for these adapter", "for these adapter /", "these adapter / co", "adapter / co activator", "/ co activator proteins", "co activator proteins now", "activator proteins now labels", "proteins now labels them", "now labels them mediator", "labels them mediator 1", "them mediator 1 through", "mediator 1 through mediator", "1 through mediator 31", "mediator 31 bourbon", "2004 . for", "the drip205 / trap220", "drip205 / trap220 proteins", "/ trap220 proteins are", "trap220 proteins are now", "proteins are now identified", "are now identified as", "now identified as mediator", "identified as mediator 1", "mediator 1 rachez", "1999 based", "based on homology with", "on homology with yeast", "homology with yeast mediator", "with yeast mediator 1.

", "yeast mediator 1.

example", "mediator 1.

example pathway:", "1.

example pathway: specific", "example pathway: specific regulation", "pathway: specific regulation of", "specific regulation of target", "regulation of target genes", "of target genes during", "target genes during notch", "genes during notch signaling:", "during notch signaling:

one", "notch signaling:

one well", "signaling:

one well studied", "

one well studied example", "well studied example of", "studied example of cell", "example of cell specific", "of cell specific regulation", "specific regulation of gene", "regulation of gene transcription", "of gene transcription is", "gene transcription is selective", "transcription is selective regulation", "is selective regulation of", "selective regulation of target", "genes during notch signaling.", "notch signaling. notch", "signaling. notch signaling", "notch signaling was first", "signaling was first identified", "was first identified in", "first identified in drosophila", "in drosophila where", "drosophila where it", "where it has been", "it has been studied", "has been studied in", "been studied in detail", "studied in detail at", "in detail at the", "detail at the genetic", "the genetic molecular", "molecular biochemical and", "biochemical and cellular levels", "cellular levels reviewed", "levels reviewed in", "in justice 2002", "louvri 2006 .", "2006 . in", ". in drosophila", "in drosophila notch", "drosophila notch signaling", "notch signaling to the", "signaling to the nucleus", "to the nucleus is", "the nucleus is thought", "nucleus is thought always", "is thought always to", "thought always to be", "always to be mediated", "to be mediated by", "be mediated by one", "mediated by one specific", "by one specific dna", "one specific dna binding", "specific dna binding transcription", "dna binding transcription factor", "transcription factor suppressor", "factor suppressor of", "of hairless. in", "hairless. in mammals", "in mammals the", "mammals the homologous", "the homologous genes are", "homologous genes are called", "genes are called cbf1", "called cbf1 or", "cbf1 or rbpjkappa", "rbpjkappa while", "while in worms they", "in worms they are", "worms they are called", "they are called lag", "are called lag 1", "lag 1 so", "1 so that", "so that the acronym", "that the acronym \\csl\\", "the acronym \\csl\\ has", "acronym \\csl\\ has been", "\\csl\\ has been given", "has been given to", "been given to this", "given to this conserved", "to this conserved transcription", "this conserved transcription factor", "conserved transcription factor family.", "factor family. there", "family. there are", "at least two human", "least two human csl", "two human csl homologues", "csl homologues which", "homologues which are", "which are now named", "are now named rbpj", "now named rbpj and", "named rbpj and rbpjl.", "and rbpjl.

in", "rbpjl.

in drosophila", "

in drosophila su", "drosophila su h", "su h is", "h is known", "is known to be", "known to be bifunctional", "be bifunctional in", "bifunctional in that", "in that it represses", "that it represses target", "it represses target gene", "represses target gene transcription", "target gene transcription in", "gene transcription in the", "transcription in the absence", "in the absence of", "the absence of notch", "absence of notch signaling", "notch signaling but", "signaling but activates", "but activates target genes", "activates target genes during", "notch signaling. at", "signaling. at least", "at least some of", "least some of the", "some of the mammalian", "of the mammalian csl", "the mammalian csl homologues", "mammalian csl homologues are", "csl homologues are believed", "homologues are believed also", "are believed also to", "believed also to be", "also to be bifunctional", "be bifunctional and", "bifunctional and to", "and to mediate target", "to mediate target gene", "mediate target gene repression", "target gene repression in", "gene repression in the", "repression in the absence", "notch signaling and", "signaling and activation", "and activation in the", "activation in the presence", "in the presence of", "the presence of notch", "presence of notch signaling.

notch", "of notch signaling.

notch co", "notch signaling.

notch co activator", "signaling.

notch co activator and", "co activator and co", "co repressor complexes: this", "repressor complexes: this repression", "complexes: this repression is", "this repression is mediated", "repression is mediated by", "is mediated by at", "mediated by at least", "by at least one", "at least one specific", "least one specific co", "one specific co repressor", "specific co repressor complexes", "repressor complexes co", "complexes co r", "co r bound", "r bound to", "bound to csl in", "to csl in the", "csl in the absence", "absence of notch signaling.", "notch signaling. in", "signaling. in drosophila", "in drosophila this", "drosophila this co", "this co repressor complex", "co repressor complex consists", "repressor complex consists of", "complex consists of at", "consists of at least", "of at least three", "at least three distinct", "least three distinct co", "three distinct co repressor", "distinct co repressor proteins:", "co repressor proteins: hairless", "proteins: hairless groucho", "and dctbp drosophila", "dctbp drosophila c", "drosophila c terminal binding", "c terminal binding protein", "terminal binding protein .", "protein . hairless", ". hairless has", "hairless has been show", "has been show to", "been show to bind", "show to bind directly", "to bind directly to", "bind directly to su", "directly to su h", "h and", "and groucho and dctbp", "groucho and dctbp have", "and dctbp have been", "dctbp have been shown", "have been shown to", "been shown to bind", "shown to bind directly", "bind directly to hairless", "to hairless barolo", "barolo 2002 .", "2002 . all", ". all three", "all three of the", "three of the co", "of the co repressor", "the co repressor proteins", "co repressor proteins have", "repressor proteins have been", "proteins have been shown", "been shown to be", "shown to be necessary", "to be necessary for", "be necessary for proper", "necessary for proper gene", "for proper gene regulation", "proper gene regulation during", "gene regulation during notch", "regulation during notch signaling", "during notch signaling in", "notch signaling in vivo", "in vivo nagel", "nagel 2005 .

in", ".

in mammals the", "mammals the same", "the same general pathway", "same general pathway and", "general pathway and mechanisms", "pathway and mechanisms are", "and mechanisms are observed", "are observed where", "observed where csl", "where csl proteins are", "csl proteins are bifunctional", "proteins are bifunctional dna", "are bifunctional dna binding", "bifunctional dna binding transcription", "tfs that", "that bind to co", "bind to co repressor", "to co repressor complexes", "co repressor complexes to", "repressor complexes to mediate", "complexes to mediate repression", "to mediate repression in", "mediate repression in the", "signaling and bind", "and bind to co", "bind to co activator", "activator complexes to", "complexes to mediate activation", "to mediate activation in", "mediate activation in the", "presence of notch signaling.", "notch signaling. however", "however in mammals", "in mammals there", "mammals there may", "there may be multiple", "may be multiple co", "be multiple co repressor", "multiple co repressor complexes", "repressor complexes rather", "complexes rather than", "rather than the single", "than the single hairless", "the single hairless co", "single hairless co repressor", "hairless co repressor complex", "co repressor complex that", "repressor complex that has", "complex that has been", "that has been observed", "has been observed in", "been observed in drosophila.", "in drosophila.

during", "drosophila.

during notch", "

during notch signaling in", "notch signaling in all", "signaling in all systems", "all systems the", "systems the notch", "the notch transmembrane receptor", "notch transmembrane receptor is", "transmembrane receptor is cleaved", "receptor is cleaved and", "is cleaved and the", "cleaved and the notch", "and the notch intracellular", "the notch intracellular domain", "intracellular domain nicd", "nicd translocates to", "translocates to the nucleus", "the nucleus where", "nucleus where it", "where it there functions", "it there functions as", "there functions as a", "functions as a specific", "as a specific transcription", "a specific transcription co", "transcription co activator for", "co activator for csl", "activator for csl proteins.", "csl proteins. in", "proteins. in the", "the nucleus nicd", "nucleus nicd replaces", "nicd replaces the co", "replaces the co r", "the co r complex", "co r complex bound", "r complex bound to", "complex bound to csl", "to csl thus", "csl thus resulting", "thus resulting in de", "resulting in de repression", "in de repression of", "repression of notch", "of notch target", "notch target genes in", "target genes in the", "genes in the nucleus", "the nucleus figure", "nucleus figure 2", "2 . once", ". once bound", "once bound to csl", "to csl nicd", "csl nicd and", "nicd and csl proteins", "and csl proteins recruit", "csl proteins recruit an", "proteins recruit an additional", "recruit an additional co", "an additional co activator", "additional co activator protein", "activator protein mastermind", "mastermind to form", "to form a csl", "form a csl nicd", "a csl nicd mam", "csl nicd mam ternary", "nicd mam ternary co", "mam ternary co activator", "co a complex.", "complex. this co", "r complex was", "complex was initially thought", "was initially thought to", "initially thought to be", "thought to be sufficient", "to be sufficient to", "be sufficient to mediate", "sufficient to mediate activation", "to mediate activation of", "activation of at", "at least some notch", "least some notch target", "some notch target genes.", "target genes. however", "however there now", "there now is evidence", "now is evidence that", "is evidence that still", "evidence that still other", "that still other co", "still other co activators", "other co activators and", "co activators and additional", "activators and additional dna", "and additional dna binding", "additional dna binding transcription", "binding transcription factors are", "transcription factors are required", "factors are required in", "are required in at", "required in at least", "at least some contexts", "some contexts reviewed", "contexts reviewed in", "in barolo 2002", "2002 .

thus", "

thus csl is", "csl is a good", "is a good example", "a good example of", "good example of a", "example of a bifunctional", "of a bifunctional dna", "a bifunctional dna binding", "binding transcription factor that", "transcription factor that mediates", "factor that mediates repression", "that mediates repression of", "mediates repression of specific", "repression of specific targets", "of specific targets genes", "specific targets genes in", "targets genes in one", "genes in one context", "one context but", "context but activation", "but activation of the", "activation of the same", "of the same targets", "the same targets in", "same targets in another", "targets in another context.", "another context. this", "context. this bifunctionality", "this bifunctionality is mediated", "bifunctionality is mediated by", "is mediated by the", "mediated by the association", "by the association of", "the association of specific", "association of specific co", "of specific co repressor", "co repressor complexes vs.", "repressor complexes vs. specific", "complexes vs. specific co", "vs. specific co activator", "co activator complexes in", "activator complexes in different", "complexes in different contexts", "different contexts namely", "contexts namely in", "namely in the absence", "in the absence or", "the absence or presence", "absence or presence of", "or presence of notch", "of transcription regulation:

detailed", "transcription regulation:

detailed studies", "regulation:

detailed studies of", "

detailed studies of gene transcription", "studies of gene transcription regulation", "of gene transcription regulation in", "gene transcription regulation in a", "transcription regulation in a wide", "regulation in a wide variety", "in a wide variety of", "a wide variety of eukaryotic", "wide variety of eukaryotic systems", "variety of eukaryotic systems has", "of eukaryotic systems has revealed", "eukaryotic systems has revealed the", "systems has revealed the general", "has revealed the general principles", "revealed the general principles and", "the general principles and mechanisms", "general principles and mechanisms by", "principles and mechanisms by which", "and mechanisms by which cell", "by which cell or", "which cell or tissue", "or tissue specific regulation of", "tissue specific regulation of differential", "specific regulation of differential gene", "regulation of differential gene transcription", "of differential gene transcription is", "differential gene transcription is mediated", "transcription is mediated reviewed", "is mediated reviewed in", "mediated reviewed in naar", "reviewed in naar 2001.", "in naar 2001. kadonaga", "kadonaga 2004 maston", "2004 maston 2006", "maston 2006 barolo", "2006 barolo 2002", "barolo 2002 roeder", "2002 roeder 2005", "roeder 2005 rosenfeld", "2005 rosenfeld 2006", "2006 . of the", ". of the three", "of the three major classes", "the three major classes of", "three major classes of dna", "major classes of dna polymerase", "classes of dna polymerase involved", "of dna polymerase involved in", "dna polymerase involved in eukaryotic", "polymerase involved in eukaryotic gene", "involved in eukaryotic gene transcription", "eukaryotic gene transcription polymerase", "gene transcription polymerase ii", "transcription polymerase ii generally", "polymerase ii generally regulates protein", "ii generally regulates protein encoding", "generally regulates protein encoding genes.", "encoding genes. figure", "genes. figure 1", "figure 1 shows a diagram", "1 shows a diagram of", "shows a diagram of the", "a diagram of the various", "diagram of the various components", "of the various components involved", "the various components involved in", "various components involved in cell", "components involved in cell specific", "involved in cell specific regulation", "in cell specific regulation of", "cell specific regulation of pol", "specific regulation of pol ii", "regulation of pol ii gene", "of pol ii gene transcription.", "pol ii gene transcription.

core", "ii gene transcription.

core promoter:", "gene transcription.

core promoter: pol", "transcription.

core promoter: pol ii", "

core promoter: pol ii regulated", "promoter: pol ii regulated genes", "pol ii regulated genes typically", "ii regulated genes typically have", "regulated genes typically have a", "genes typically have a core", "typically have a core promoter", "have a core promoter where", "a core promoter where pol", "core promoter where pol ii", "promoter where pol ii and", "where pol ii and a", "pol ii and a variety", "ii and a variety of", "and a variety of general", "a variety of general factors", "variety of general factors bind", "of general factors bind to", "general factors bind to specific", "factors bind to specific dna", "bind to specific dna motifs:", "to specific dna motifs:
", "motifs:
i:", "
i: the", "the tata box tata", "tata box tata dna", "box tata dna sequence", "dna sequence which", "sequence which is", "which is bound by the", "is bound by the \\tata", "bound by the \\tata binding", "by the \\tata binding protein\\", "\\tata binding protein\\ tbp", "binding protein\\ tbp .
", "tbp .
ii:", ".
ii: the", "the initiator motif inr", "inr where pol", "where pol ii and certain", "pol ii and certain other", "ii and certain other core", "and certain other core factors", "certain other core factors bind", "core factors bind is", "factors bind is present", "bind is present in", "is present in many pol", "present in many pol ii", "in many pol ii regulated", "many pol ii regulated genes.
", "regulated genes.
iii:", "genes.
iii: the", "iii: the downstream promoter element", "downstream promoter element dpe", "dpe which is", "which is present in a", "is present in a subset", "present in a subset of", "in a subset of pol", "a subset of pol ii", "subset of pol ii genes", "pol ii genes and", "ii genes and where", "genes and where additional", "and where additional core factors", "where additional core factors bind.", "core factors bind.
the", "factors bind.
the core", "bind.
the core promoter", "
the core promoter binding factors", "core promoter binding factors are", "promoter binding factors are generally", "binding factors are generally ubiquitously", "factors are generally ubiquitously expressed", "generally ubiquitously expressed although", "ubiquitously expressed although there", "expressed although there are", "although there are exceptions to", "there are exceptions to this.

proximal", "are exceptions to this.

proximal promoter:", "exceptions to this.

proximal promoter: immediately", "to this.

proximal promoter: immediately upstream", "promoter: immediately upstream 5'", "upstream 5' of", "5' of the core", "the core promoter pol", "core promoter pol ii", "promoter pol ii target", "pol ii target genes often", "ii target genes often have", "target genes often have a", "genes often have a proximal", "often have a proximal promoter", "have a proximal promoter region", "a proximal promoter region that", "proximal promoter region that spans", "promoter region that spans up", "region that spans up to", "that spans up to 500", "spans up to 500 base", "up to 500 base pairs", "500 base pairs b.p.", "b.p. or even", "or even to 1000 b.p..", "to 1000 b.p.. this", "1000 b.p.. this region", "b.p.. this region contains", "this region contains a number", "region contains a number of", "contains a number of functional", "a number of functional dna", "number of functional dna binding", "of functional dna binding sites", "functional dna binding sites for", "dna binding sites for a", "binding sites for a specific", "sites for a specific set", "for a specific set of", "a specific set of transcription", "specific set of transcription activator", "of transcription activator ta", "activator ta and", "ta and transcription repressor", "and transcription repressor tr", "repressor tr proteins.", "tr proteins. these", "proteins. these ta and", "these ta and tr factors", "ta and tr factors are", "and tr factors are generally", "tr factors are generally cell", "are generally cell or", "generally cell or tissue", "or tissue specific in expression", "specific in expression rather", "in expression rather than", "expression rather than ubiquitous", "rather than ubiquitous so", "than ubiquitous so that", "ubiquitous so that the", "so that the presence of", "that the presence of their", "the presence of their cognate", "presence of their cognate binding", "of their cognate binding sites", "their cognate binding sites in", "cognate binding sites in the", "binding sites in the proximal", "sites in the proximal promoter", "in the proximal promoter region", "the proximal promoter region programs", "proximal promoter region programs cell", "region programs cell or", "programs cell or tissue", "or tissue specific expression of", "tissue specific expression of the", "specific expression of the target", "expression of the target gene", "the target gene perhaps", "target gene perhaps in", "gene perhaps in conjunction", "perhaps in conjunction with ta", "in conjunction with ta and", "conjunction with ta and tr", "with ta and tr complexes", "ta and tr complexes bound", "and tr complexes bound in", "tr complexes bound in distal", "complexes bound in distal enhancer", "bound in distal enhancer regions.", "distal enhancer regions.

distal", "enhancer regions.

distal enhancer", "regions.

distal enhancer s", "

distal enhancer s : many", "enhancer s : many or", "s : many or most", ": many or most pol", "many or most pol ii", "or most pol ii regulated", "most pol ii regulated genes", "pol ii regulated genes in", "ii regulated genes in higher", "regulated genes in higher eukaryotes", "genes in higher eukaryotes have", "in higher eukaryotes have one", "higher eukaryotes have one or", "eukaryotes have one or more", "have one or more distal", "one or more distal enhancer", "or more distal enhancer regions", "more distal enhancer regions which", "distal enhancer regions which are", "enhancer regions which are essential", "regions which are essential for", "which are essential for proper", "are essential for proper regulation", "essential for proper regulation of", "for proper regulation of the", "proper regulation of the gene", "of the gene often", "the gene often in", "gene often in a", "often in a cell or", "in a cell or tissue", "a cell or tissue specific", "cell or tissue specific pattern.", "tissue specific pattern. like", "specific pattern. like the", "pattern. like the proximal", "like the proximal promoter region", "proximal promoter region each", "promoter region each of", "region each of the", "each of the distal enhancer", "of the distal enhancer regions", "the distal enhancer regions typically", "distal enhancer regions typically contain", "enhancer regions typically contain a", "regions typically contain a cluster", "typically contain a cluster of", "contain a cluster of binding", "a cluster of binding sites", "cluster of binding sites for", "of binding sites for specific", "binding sites for specific ta", "sites for specific ta and/or", "for specific ta and/or tr", "specific ta and/or tr dna", "ta and/or tr dna binding", "and/or tr dna binding factors", "dna binding factors rather", "binding factors rather than", "factors rather than just", "rather than just a single", "than just a single site.", "just a single site.

", "site.

enhancers", "

enhancers generally", "enhancers generally have three defining", "generally have three defining characteristics:
", "i: they can be located", "they can be located very", "can be located very long", "be located very long distances", "located very long distances from", "very long distances from the", "long distances from the promoter", "distances from the promoter of", "from the promoter of the", "the promoter of the target", "promoter of the target gene", "of the target gene they", "the target gene they regulate", "gene they regulate sometimes", "they regulate sometimes as", "regulate sometimes as far", "sometimes as far as 100", "as far as 100 kb", "as 100 kb or", "100 kb or more.
", "ii: they can be either", "they can be either upstream", "be either upstream 5'", "upstream 5' or", "downstream 3' of", "3' of the target", "the target gene including", "target gene including within", "gene including within introns", "including within introns of that", "within introns of that gene.
", "iii: they can function in", "they can function in either", "can function in either orientation", "function in either orientation in", "in either orientation in the", "either orientation in the dna.

combinatorial", "orientation in the dna.

combinatorial mechanisms", "in the dna.

combinatorial mechanisms of", "the dna.

combinatorial mechanisms of transcription", "dna.

combinatorial mechanisms of transcription regulation:", "mechanisms of transcription regulation: the", "of transcription regulation: the specific", "transcription regulation: the specific combination", "regulation: the specific combination of", "the specific combination of ta", "specific combination of ta and", "combination of ta and tr", "of ta and tr binding", "ta and tr binding sites", "and tr binding sites within", "tr binding sites within the", "binding sites within the proximal", "sites within the proximal promoter", "within the proximal promoter and/or", "the proximal promoter and/or distal", "proximal promoter and/or distal enhancer", "promoter and/or distal enhancer s", "distal enhancer s provides", "enhancer s provides a", "s provides a \\combinatorial", "provides a \\combinatorial transcription code\\", "a \\combinatorial transcription code\\ that", "\\combinatorial transcription code\\ that mediates", "transcription code\\ that mediates cell", "that mediates cell or", "mediates cell or tissue", "specific expression of the associated", "expression of the associated target", "of the associated target gene.", "associated target gene. each", "target gene. each promoter", "gene. each promoter or", "each promoter or enhancer region", "promoter or enhancer region mediates", "or enhancer region mediates expression", "enhancer region mediates expression in", "region mediates expression in a", "mediates expression in a specific", "expression in a specific subset", "in a specific subset of", "a specific subset of the", "specific subset of the overall", "subset of the overall expression", "of the overall expression pattern.", "overall expression pattern. in", "expression pattern. in at", "pattern. in at least", "in at least some cases", "least some cases each", "some cases each enhancer", "cases each enhancer region", "each enhancer region functions completely", "enhancer region functions completely independently", "region functions completely independently of", "functions completely independently of the", "completely independently of the others", "of the others so", "the others so that", "others so that the", "so that the overall expression", "that the overall expression pattern", "the overall expression pattern is", "overall expression pattern is a", "expression pattern is a linear", "pattern is a linear combination", "is a linear combination of", "a linear combination of the", "linear combination of the expression", "combination of the expression patterns", "of the expression patterns of", "the expression patterns of each", "expression patterns of each of", "patterns of each of the", "of each of the enhancer", "each of the enhancer modules.

co", "of the enhancer modules.

co activator", "the enhancer modules.

co activator and", "enhancer modules.

co activator and co", "modules.

co activator and co repressor", "activator and co repressor complexes:", "co repressor complexes: dna", "repressor complexes: dna bound", "complexes: dna bound ta", "dna bound ta and tr", "bound ta and tr proteins", "ta and tr proteins typically", "and tr proteins typically recruit", "tr proteins typically recruit the", "proteins typically recruit the assembly", "typically recruit the assembly of", "recruit the assembly of specific", "the assembly of specific co", "assembly of specific co activator", "specific co activator co", "co activator co a", "co a and co", "a and co repressor", "and co repressor co", "co repressor co r", "r complexes respectively", "complexes respectively which", "respectively which are essential", "which are essential for regulating", "are essential for regulating target", "essential for regulating target gene", "for regulating target gene transcription.", "target gene transcription. both", "gene transcription. both co", "transcription. both co a's", "both co a's and co", "co a's and co r's", "and co r's are", "co r's are multi", "r's are multi protein", "are multi protein complexes that", "multi protein complexes that contain", "protein complexes that contain several", "complexes that contain several specific", "that contain several specific protein", "contain several specific protein components.

co", "several specific protein components.

co activator", "specific protein components.

co activator complexes", "protein components.

co activator complexes generally", "components.

co activator complexes generally contain", "activator complexes generally contain at", "complexes generally contain at lease", "generally contain at lease one", "contain at lease one component", "at lease one component protein", "lease one component protein that", "one component protein that has", "component protein that has histone", "protein that has histone acetyl", "that has histone acetyl transferase", "histone acetyl transferase hat", "transferase hat enzymatic", "enzymatic activity. this functions", "activity. this functions to", "this functions to acetylate histones", "functions to acetylate histones and/or", "to acetylate histones and/or other", "acetylate histones and/or other chromatin", "histones and/or other chromatin associated", "and/or other chromatin associated factors", "chromatin associated factors which", "associated factors which typically", "factors which typically increases", "which typically increases that transcription", "typically increases that transcription activation", "increases that transcription activation of", "that transcription activation of the", "transcription activation of the target", "activation of the target gene.", "the target gene. by", "target gene. by contrast", "by contrast co repressor", "contrast co repressor complexes", "co repressor complexes generally contain", "repressor complexes generally contain at", "protein that has histone de", "that has histone de acetylase", "histone de acetylase hdac", "acetylase hdac enzymatic", "this functions to de acetylate", "functions to de acetylate histones", "to de acetylate histones and/or", "de acetylate histones and/or other", "and/or other chromatin associated factors.", "other chromatin associated factors. this", "chromatin associated factors. this typically", "associated factors. this typically increases", "factors. this typically increases the", "this typically increases the transcription", "typically increases the transcription repression", "increases the transcription repression of", "the transcription repression of the", "transcription repression of the target", "repression of the target gene.

adaptor", "the target gene.

adaptor mediator", "gene.

adaptor mediator complexes:", "mediator complexes: in addition", "complexes: in addition to the", "in addition to the co", "addition to the co activator", "to the co activator complexes", "the co activator complexes that", "co activator complexes that assemble", "activator complexes that assemble on", "complexes that assemble on particular", "that assemble on particular cell", "assemble on particular cell specific", "on particular cell specific ta", "particular cell specific ta factors", "there are at least two", "are at least two additional", "at least two additional transcriptional", "least two additional transcriptional co", "two additional transcriptional co activator", "additional transcriptional co activator complexes", "transcriptional co activator complexes common", "co activator complexes common to", "activator complexes common to most", "complexes common to most cells.", "to most cells. one", "most cells. one of", "cells. one of these", "one of these is the", "of these is the mediator", "these is the mediator complex", "the mediator complex which", "mediator complex which functions", "complex which functions as", "which functions as an \\adaptor\\", "functions as an \\adaptor\\ complex", "as an \\adaptor\\ complex that", "an \\adaptor\\ complex that bridges", "\\adaptor\\ complex that bridges between", "complex that bridges between the", "that bridges between the tissue", "bridges between the tissue specific", "between the tissue specific co", "the tissue specific co activator", "tissue specific co activator complexes", "specific co activator complexes assembled", "co activator complexes assembled in", "activator complexes assembled in the", "complexes assembled in the proximal", "assembled in the proximal promoter", "the proximal promoter or", "proximal promoter or distal", "promoter or distal enhancers", "distal enhancers . the", "enhancers . the human", ". the human mediator", "the human mediator complex has", "human mediator complex has been", "mediator complex has been shown", "complex has been shown to", "has been shown to contain", "been shown to contain at", "shown to contain at least", "to contain at least 19", "contain at least 19 protein", "at least 19 protein distinct", "least 19 protein distinct components.", "protein distinct components. different", "distinct components. different combinations", "components. different combinations of", "different combinations of these co", "combinations of these co activator", "of these co activator proteins", "these co activator proteins are", "co activator proteins are also", "activator proteins are also found", "proteins are also found to", "are also found to be", "also found to be components", "found to be components of", "to be components of specific", "be components of specific transcription", "components of specific transcription co", "of specific transcription co activator", "specific transcription co activator complexes", "co activator complexes such", "activator complexes such as", "complexes such as the", "as the drip trap", "the drip trap and", "drip trap and arc", "trap and arc complexes described", "and arc complexes described below.", "complexes described below.

tbp/taf", "described below.

tbp/taf complex:", "below.

tbp/taf complex: another", "

tbp/taf complex: another large co", "complex: another large co a", "another large co a complex", "large co a complex is", "co a complex is the", "a complex is the \\tbp", "complex is the \\tbp associated", "is the \\tbp associated factors\\", "\\tbp associated factors\\ tafs", "factors\\ tafs that", "tafs that assemble on", "assemble on tbp tata", "on tbp tata binding", "tbp tata binding protein", "binding protein which", "protein which is", "which is bound to the", "is bound to the tata", "bound to the tata box", "to the tata box present", "the tata box present in", "tata box present in many", "box present in many promoters.", "in many promoters. there", "many promoters. there are", "promoters. there are at", "there are at least 23", "are at least 23 human", "at least 23 human taf", "least 23 human taf proteins", "23 human taf proteins that", "human taf proteins that have", "taf proteins that have been", "proteins that have been identified.", "have been identified. many", "been identified. many of", "identified. many of these", "many of these are ubiquitously", "of these are ubiquitously expressed", "are ubiquitously expressed but", "ubiquitously expressed but tafs", "expressed but tafs can", "but tafs can also be", "tafs can also be expressed", "can also be expressed in", "also be expressed in a", "be expressed in a cell", "expressed in a cell or", "tissue specific pattern.

", "specific pattern.

\tspecific", "pattern.

\tspecific coactivator", "

\tspecific coactivator complexes for", "\tspecific coactivator complexes for dna", "coactivator complexes for dna binding", "complexes for dna binding transcription", "for dna binding transcription factors.", "transcription factors.

a", "factors.

a number", "

a number of specific co", "number of specific co activator", "of specific co activator complexes", "specific co activator complexes for", "co activator complexes for dna", "activator complexes for dna binding", "for dna binding transcription factors", "dna binding transcription factors have", "binding transcription factors have been", "transcription factors have been identified", "have been identified including", "been identified including drip", "and arc reviewed in", "arc reviewed in bourbon", "reviewed in bourbon 2004", "bourbon 2004 blazek", "2004 blazek 2005", "blazek 2005 conaway", "2005 conaway 2005", "conaway 2005 and", "and malik 2005 .", "2005 . the drip", ". the drip co", "the drip co activator complex", "drip co activator complex was", "co activator complex was originally", "activator complex was originally identified", "complex was originally identified and", "was originally identified and named", "originally identified and named as", "identified and named as a", "and named as a specific", "named as a specific complex", "as a specific complex associated", "a specific complex associated with", "specific complex associated with the", "complex associated with the vitamin", "associated with the vitamin d", "with the vitamin d receptor", "the vitamin d receptor member", "vitamin d receptor member of", "d receptor member of the", "receptor member of the nuclear", "member of the nuclear receptor", "of the nuclear receptor family", "the nuclear receptor family of", "nuclear receptor family of transcription", "receptor family of transcription factors", "of transcription factors rachez", "factors rachez 1998", ". similarly the", "similarly the trap co", "the trap co activator complex", "trap co activator complex was", "complex was originally identified as", "was originally identified as a", "originally identified as a complex", "identified as a complex that", "as a complex that associates", "a complex that associates with", "complex that associates with the", "that associates with the thyroid", "associates with the thyroid receptor", "the thyroid receptor yuan", "receptor yuan 1998", "1998 . it", ". it was", "it was later determined that", "was later determined that all", "later determined that all of", "determined that all of the", "that all of the components", "all of the components of", "of the components of the", "the components of the drip", "components of the drip complex", "of the drip complex are", "the drip complex are also", "drip complex are also present", "complex are also present in", "are also present in the", "also present in the trap", "present in the trap complex", "the trap complex and", "trap complex and the", "complex and the arc", "the arc complex discussed", "arc complex discussed further", "complex discussed further below", "further below . for", "below . for example", "for example the drip205", "example the drip205 and", "the drip205 and trap220 proteins", "drip205 and trap220 proteins were", "and trap220 proteins were show", "trap220 proteins were show to", "proteins were show to be", "were show to be identical", "to be identical as", "be identical as were", "identical as were specific", "as were specific pairs of", "were specific pairs of the", "specific pairs of the other", "pairs of the other components", "of the other components of", "the other components of these", "other components of these complexes", "of these complexes rachez", "complexes rachez 1999", "rachez 1999 .

in addition", "1999 .

in addition these", ".

in addition these various", "addition these various transcription", "these various transcription co activator", "various transcription co activator proteins", "transcription co activator proteins identified", "co activator proteins identified in", "activator proteins identified in mammalian", "proteins identified in mammalian cells", "identified in mammalian cells were", "in mammalian cells were found", "mammalian cells were found to", "cells were found to be", "were found to be the", "found to be the orthologues", "to be the orthologues or", "be the orthologues or homologues", "the orthologues or homologues of", "orthologues or homologues of the", "or homologues of the mediator", "of the mediator \\adaptor\\", "mediator \\adaptor\\ complex", "complex proteins reviewed in", "proteins reviewed in bourbon", "in bourbon 2004 .", "2004 . the mediator", ". the mediator proteins", "the mediator proteins were originally", "mediator proteins were originally identified", "proteins were originally identified in", "were originally identified in yeast", "identified in yeast by", "in yeast by kornberg", "yeast by kornberg and", "kornberg and colleagues as", "and colleagues as complexes", "colleagues as complexes associated", "as complexes associated with dna", "complexes associated with dna polymerase", "with dna polymerase kelleher", "polymerase kelleher 1990", "1990 . in higher", ". in higher organisms", "in higher organisms adapter", "higher organisms adapter complexes", "organisms adapter complexes bridge", "adapter complexes bridge between the", "complexes bridge between the basal", "bridge between the basal transcription", "between the basal transcription factors", "basal transcription factors including", "transcription factors including pol", "factors including pol ii", "including pol ii and", "pol ii and tissue", "ii and tissue specific", "and tissue specific transcription factors", "specific transcription factors tfs", "factors tfs bound", "tfs bound to sites", "bound to sites within upstream", "to sites within upstream proximal", "sites within upstream proximal promoter", "within upstream proximal promoter regions", "upstream proximal promoter regions or", "proximal promoter regions or distal", "promoter regions or distal enhancer", "regions or distal enhancer regions", "distal enhancer regions figure", "enhancer regions figure 1", "regions figure 1 .", "figure 1 . however", ". however many", "however many of the", "many of the mediator homologues", "of the mediator homologues can", "the mediator homologues can also", "mediator homologues can also be", "homologues can also be found", "can also be found in", "also be found in complexes", "be found in complexes associated", "found in complexes associated with", "in complexes associated with specific", "complexes associated with specific transcription", "associated with specific transcription factors", "with specific transcription factors in", "specific transcription factors in higher", "transcription factors in higher organisms.", "in higher organisms. a", "higher organisms. a unified", "organisms. a unified nomenclature", "a unified nomenclature system for", "unified nomenclature system for these", "nomenclature system for these adapter", "system for these adapter /", "for these adapter / co", "these adapter / co activator", "adapter / co activator proteins", "/ co activator proteins now", "co activator proteins now labels", "activator proteins now labels them", "proteins now labels them mediator", "now labels them mediator 1", "labels them mediator 1 through", "them mediator 1 through mediator", "mediator 1 through mediator 31", "through mediator 31 bourbon", "31 bourbon 2004", "2004 . for example", "example the drip205 /", "the drip205 / trap220 proteins", "drip205 / trap220 proteins are", "/ trap220 proteins are now", "trap220 proteins are now identified", "proteins are now identified as", "are now identified as mediator", "now identified as mediator 1", "as mediator 1 rachez", "1 rachez 1999", "1999 based on", "based on homology with yeast", "on homology with yeast mediator", "homology with yeast mediator 1.

", "with yeast mediator 1.

example", "yeast mediator 1.

example pathway:", "mediator 1.

example pathway: specific", "1.

example pathway: specific regulation", "example pathway: specific regulation of", "pathway: specific regulation of target", "specific regulation of target genes", "regulation of target genes during", "of target genes during notch", "target genes during notch signaling:", "genes during notch signaling:

one", "during notch signaling:

one well", "notch signaling:

one well studied", "signaling:

one well studied example", "

one well studied example of", "well studied example of cell", "studied example of cell specific", "example of cell specific regulation", "of cell specific regulation of", "cell specific regulation of gene", "specific regulation of gene transcription", "regulation of gene transcription is", "of gene transcription is selective", "gene transcription is selective regulation", "transcription is selective regulation of", "is selective regulation of target", "selective regulation of target genes", "target genes during notch signaling.", "during notch signaling. notch", "notch signaling. notch signaling", "signaling. notch signaling was", "notch signaling was first identified", "signaling was first identified in", "was first identified in drosophila", "identified in drosophila where", "in drosophila where it", "drosophila where it has", "where it has been studied", "it has been studied in", "has been studied in detail", "been studied in detail at", "studied in detail at the", "in detail at the genetic", "at the genetic molecular", "genetic molecular biochemical", "molecular biochemical and cellular", "and cellular levels reviewed", "cellular levels reviewed in", "levels reviewed in justice", "reviewed in justice 2002", "justice 2002 bray", "2002 bray 2006", "bray 2006 schweisguth", "2006 schweisguth 2004", "schweisguth 2004 louvri", "2004 louvri 2006", "2006 . in drosophila", "in drosophila notch signaling", "drosophila notch signaling to", "notch signaling to the nucleus", "signaling to the nucleus is", "to the nucleus is thought", "the nucleus is thought always", "nucleus is thought always to", "is thought always to be", "thought always to be mediated", "always to be mediated by", "to be mediated by one", "be mediated by one specific", "mediated by one specific dna", "by one specific dna binding", "one specific dna binding transcription", "specific dna binding transcription factor", "binding transcription factor suppressor", "transcription factor suppressor of", "factor suppressor of hairless.", "suppressor of hairless. in", "of hairless. in mammals", "in mammals the homologous", "mammals the homologous genes", "the homologous genes are called", "homologous genes are called cbf1", "are called cbf1 or", "called cbf1 or rbpjkappa", "or rbpjkappa while", "rbpjkappa while in", "while in worms they are", "in worms they are called", "worms they are called lag", "they are called lag 1", "called lag 1 so", "lag 1 so that", "1 so that the", "so that the acronym \\csl\\", "that the acronym \\csl\\ has", "the acronym \\csl\\ has been", "acronym \\csl\\ has been given", "\\csl\\ has been given to", "has been given to this", "been given to this conserved", "given to this conserved transcription", "to this conserved transcription factor", "this conserved transcription factor family.", "transcription factor family. there", "factor family. there are", "family. there are at", "are at least two human", "at least two human csl", "least two human csl homologues", "human csl homologues which", "csl homologues which are", "homologues which are now", "which are now named rbpj", "are now named rbpj and", "now named rbpj and rbpjl.", "rbpj and rbpjl.

in", "and rbpjl.

in drosophila", "

in drosophila su h", "su h is known", "h is known to", "is known to be bifunctional", "to be bifunctional in", "be bifunctional in that", "bifunctional in that it", "in that it represses target", "that it represses target gene", "it represses target gene transcription", "represses target gene transcription in", "target gene transcription in the", "gene transcription in the absence", "transcription in the absence of", "in the absence of notch", "the absence of notch signaling", "of notch signaling but", "notch signaling but activates", "signaling but activates target", "but activates target genes during", "activates target genes during notch", "during notch signaling. at", "notch signaling. at least", "signaling. at least some", "at least some of the", "least some of the mammalian", "some of the mammalian csl", "of the mammalian csl homologues", "the mammalian csl homologues are", "mammalian csl homologues are believed", "csl homologues are believed also", "homologues are believed also to", "are believed also to be", "believed also to be bifunctional", "to be bifunctional and", "be bifunctional and to", "bifunctional and to mediate", "and to mediate target gene", "to mediate target gene repression", "mediate target gene repression in", "target gene repression in the", "gene repression in the absence", "repression in the absence of", "of notch signaling and", "notch signaling and activation", "signaling and activation in", "and activation in the presence", "activation in the presence of", "in the presence of notch", "the presence of notch signaling.

notch", "presence of notch signaling.

notch co", "of notch signaling.

notch co activator", "notch signaling.

notch co activator and", "signaling.

notch co activator and co", "co activator and co repressor", "and co repressor complexes: this", "co repressor complexes: this repression", "repressor complexes: this repression is", "complexes: this repression is mediated", "this repression is mediated by", "repression is mediated by at", "is mediated by at least", "mediated by at least one", "by at least one specific", "at least one specific co", "least one specific co repressor", "one specific co repressor complexes", "co repressor complexes co", "repressor complexes co r", "co r bound to", "r bound to csl", "bound to csl in the", "to csl in the absence", "csl in the absence of", "the absence of notch signaling.", "of notch signaling. in", "notch signaling. in drosophila", "in drosophila this co", "drosophila this co repressor", "this co repressor complex consists", "co repressor complex consists of", "repressor complex consists of at", "complex consists of at least", "consists of at least three", "of at least three distinct", "at least three distinct co", "least three distinct co repressor", "three distinct co repressor proteins:", "distinct co repressor proteins: hairless", "repressor proteins: hairless groucho", "hairless groucho and", "and dctbp drosophila c", "dctbp drosophila c terminal", "drosophila c terminal binding protein", "c terminal binding protein .", "binding protein . hairless", "protein . hairless has", ". hairless has been", "hairless has been show to", "has been show to bind", "been show to bind directly", "show to bind directly to", "to bind directly to su", "bind directly to su h", "su h and", "h and groucho", "and groucho and dctbp have", "groucho and dctbp have been", "and dctbp have been shown", "dctbp have been shown to", "have been shown to bind", "been shown to bind directly", "shown to bind directly to", "to bind directly to hairless", "directly to hairless barolo", "hairless barolo 2002", "2002 . all three", ". all three of", "all three of the co", "three of the co repressor", "of the co repressor proteins", "the co repressor proteins have", "co repressor proteins have been", "repressor proteins have been shown", "proteins have been shown to", "have been shown to be", "been shown to be necessary", "shown to be necessary for", "to be necessary for proper", "be necessary for proper gene", "necessary for proper gene regulation", "for proper gene regulation during", "proper gene regulation during notch", "gene regulation during notch signaling", "regulation during notch signaling in", "during notch signaling in vivo", "signaling in vivo nagel", "vivo nagel 2005", "nagel 2005 .

in mammals", "2005 .

in mammals the", ".

in mammals the same", "mammals the same general", "the same general pathway and", "same general pathway and mechanisms", "general pathway and mechanisms are", "pathway and mechanisms are observed", "mechanisms are observed where", "are observed where csl", "observed where csl proteins", "where csl proteins are bifunctional", "csl proteins are bifunctional dna", "proteins are bifunctional dna binding", "are bifunctional dna binding transcription", "bifunctional dna binding transcription factors", "binding transcription factors tfs", "tfs that bind", "that bind to co repressor", "bind to co repressor complexes", "to co repressor complexes to", "co repressor complexes to mediate", "repressor complexes to mediate repression", "complexes to mediate repression in", "to mediate repression in the", "mediate repression in the absence", "notch signaling and bind", "signaling and bind to", "and bind to co activator", "to co activator complexes", "co activator complexes to", "activator complexes to mediate", "complexes to mediate activation in", "to mediate activation in the", "mediate activation in the presence", "the presence of notch signaling.", "of notch signaling. however", "signaling. however in", "in mammals there may", "mammals there may be", "there may be multiple co", "may be multiple co repressor", "be multiple co repressor complexes", "co repressor complexes rather", "repressor complexes rather than", "complexes rather than the", "rather than the single hairless", "than the single hairless co", "the single hairless co repressor", "single hairless co repressor complex", "hairless co repressor complex that", "co repressor complex that has", "repressor complex that has been", "complex that has been observed", "that has been observed in", "has been observed in drosophila.", "observed in drosophila.

during", "in drosophila.

during notch", "drosophila.

during notch signaling", "

during notch signaling in all", "notch signaling in all systems", "in all systems the", "all systems the notch", "systems the notch transmembrane", "the notch transmembrane receptor is", "notch transmembrane receptor is cleaved", "transmembrane receptor is cleaved and", "receptor is cleaved and the", "is cleaved and the notch", "cleaved and the notch intracellular", "and the notch intracellular domain", "notch intracellular domain nicd", "domain nicd translocates", "nicd translocates to the", "to the nucleus where", "the nucleus where it", "nucleus where it there", "where it there functions as", "it there functions as a", "there functions as a specific", "functions as a specific transcription", "as a specific transcription co", "a specific transcription co activator", "specific transcription co activator for", "transcription co activator for csl", "co activator for csl proteins.", "for csl proteins. in", "csl proteins. in the", "proteins. in the nucleus", "in the nucleus nicd", "the nucleus nicd replaces", "nucleus nicd replaces the", "nicd replaces the co r", "replaces the co r complex", "the co r complex bound", "co r complex bound to", "r complex bound to csl", "bound to csl thus", "to csl thus resulting", "csl thus resulting in", "thus resulting in de repression", "resulting in de repression of", "de repression of notch", "repression of notch target", "of notch target genes", "notch target genes in the", "target genes in the nucleus", "in the nucleus figure", "the nucleus figure 2", "nucleus figure 2 .", "figure 2 . once", "2 . once bound", ". once bound to", "bound to csl nicd", "to csl nicd and", "csl nicd and csl", "nicd and csl proteins recruit", "and csl proteins recruit an", "csl proteins recruit an additional", "proteins recruit an additional co", "recruit an additional co activator", "an additional co activator protein", "co activator protein mastermind", "protein mastermind to", "mastermind to form a", "to form a csl nicd", "form a csl nicd mam", "a csl nicd mam ternary", "csl nicd mam ternary co", "nicd mam ternary co activator", "ternary co activator co", "a complex. this", "complex. this co r", "this co r complex", "co r complex was", "r complex was initially", "complex was initially thought to", "was initially thought to be", "initially thought to be sufficient", "thought to be sufficient to", "to be sufficient to mediate", "be sufficient to mediate activation", "sufficient to mediate activation of", "mediate activation of at", "activation of at least", "of at least some", "at least some notch target", "least some notch target genes.", "notch target genes. however", "genes. however there", "however there now is", "there now is evidence that", "now is evidence that still", "is evidence that still other", "evidence that still other co", "that still other co activators", "still other co activators and", "other co activators and additional", "co activators and additional dna", "activators and additional dna binding", "and additional dna binding transcription", "additional dna binding transcription factors", "dna binding transcription factors are", "binding transcription factors are required", "transcription factors are required in", "factors are required in at", "are required in at least", "required in at least some", "in at least some contexts", "least some contexts reviewed", "some contexts reviewed in", "contexts reviewed in barolo", "reviewed in barolo 2002", "in barolo 2002 .", ".

thus csl", "

thus csl is a", "csl is a good example", "is a good example of", "a good example of a", "good example of a bifunctional", "example of a bifunctional dna", "of a bifunctional dna binding", "a bifunctional dna binding transcription", "bifunctional dna binding transcription factor", "dna binding transcription factor that", "binding transcription factor that mediates", "transcription factor that mediates repression", "factor that mediates repression of", "that mediates repression of specific", "mediates repression of specific targets", "repression of specific targets genes", "of specific targets genes in", "specific targets genes in one", "targets genes in one context", "in one context but", "one context but activation", "context but activation of", "but activation of the same", "activation of the same targets", "of the same targets in", "the same targets in another", "same targets in another context.", "in another context. this", "another context. this bifunctionality", "context. this bifunctionality is", "this bifunctionality is mediated by", "bifunctionality is mediated by the", "is mediated by the association", "mediated by the association of", "by the association of specific", "the association of specific co", "association of specific co repressor", "of specific co repressor complexes", "specific co repressor complexes vs.", "co repressor complexes vs. specific", "repressor complexes vs. specific co", "complexes vs. specific co activator", "vs. specific co activator complexes", "specific co activator complexes in", "co activator complexes in different", "activator complexes in different contexts", "in different contexts namely", "different contexts namely in", "contexts namely in the", "namely in the absence or", "in the absence or presence", "the absence or presence of", "absence or presence of notch", "or presence of notch signaling." ] }, { "record_id": "GLY_000594_1_213", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "212676", "r hsa", "hsa 212676", "r hsa 212676" ] }, { "record_id": "GLY_000594_1_213", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dopamine neurotransmitter", "neurotransmitter release", "release cycle", "dopamine neurotransmitter release", "neurotransmitter release cycle", "dopamine neurotransmitter release cycle", "neurotransmitter cycle", "cycle occurs", "occurs in", "in dopaminergic", "dopaminergic neurons.", "neurons. dopamine", "dopamine is", "is synthesized", "synthesized and", "and loaded", "loaded into", "into the", "the clathrin", "clathrin sculpted", "sculpted monoamine", "monoamine transport", "transport vesicles.", "vesicles. the", "the vesicles", "vesicles are", "are docked", "primed and", "and fused", "fused with", "with the", "the plasmamembrane", "plasmamembrane in", "in the", "the synapse", "synapse to", "to release", "release dopamine", "dopamine into", "the synaptic", "synaptic cleft.", "dopamine 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"proteases generating mhc", "generating mhc class ii", "mhc class ii epitopes.", "class ii epitopes. antigenic", "ii epitopes. antigenic peptides", "epitopes. antigenic peptides are", "antigenic peptides are then", "peptides are then loaded", "are then loaded into", "then loaded into the", "loaded into the class", "into the class ii", "the class ii ligand", "class ii ligand binding", "ii ligand binding groove.", "ligand binding groove. the", "binding groove. the resulting", "groove. the resulting class", "the resulting class ii", "resulting class ii peptide", "class ii peptide complexes", "ii peptide complexes then", "peptide complexes then move", "complexes then move to", "then move to the", "move to the cell", "to the cell surface", "cell surface where", "surface where they", "where they are scanned", "they are scanned by", "are scanned by cd4+", "scanned by cd4+ t", "by cd4+ t cells", "cd4+ t cells for", "t cells for specific", "cells for specific recognition", "specific recognition berger", "recognition berger &", "berger & roche 2009", "roche 2009 zhou", "2009 zhou &", "zhou & blum 2004", "blum 2004 watts", "2004 watts 2004", "watts 2004 landsverk", "2004 landsverk et", "landsverk et al. 2009", "et al. 2009 .", "antigen presenting cells apcs", "cells apcs such", "apcs such as b", "as b cells dendritic", "b cells dendritic cells", "cells dcs and", "dcs and monocytes/macrophages express", "and monocytes/macrophages express major histocompatibility", "monocytes/macrophages express major histocompatibility complex", "express major histocompatibility complex class", "major histocompatibility complex class ii", "histocompatibility complex class ii molecules", "class ii molecules mhc", "ii molecules mhc ii", "mhc ii at their", "ii at their surface", "at their surface and present", "their surface and present exogenous", "surface and present exogenous antigenic", "and present exogenous antigenic peptides", "present exogenous antigenic peptides to", "exogenous antigenic peptides to cd4+", "antigenic peptides to cd4+ t", "peptides to cd4+ t helper", "to cd4+ t helper cells.", "cd4+ t helper cells. cd4+", "t helper cells. cd4+ t", "helper cells. cd4+ t cells", "cells. cd4+ t cells play", "cd4+ t cells play a", "t cells play a central", "cells play a central role", "play a central role in", "a central role in immune", "central role in immune protection.", "role in immune protection. on", "in immune protection. on their", "immune protection. on their activation", "protection. on their activation they", "on their activation they stimulate", "their activation they stimulate differentiation", "activation they stimulate differentiation of", "they stimulate differentiation of b", "stimulate differentiation of b cells", "differentiation of b cells into", "of b cells into antibody", "b cells into antibody producing", "cells into antibody producing b", "into antibody producing b cell", "antibody producing b cell blasts", "producing b cell blasts and", "b cell blasts and initiate", "cell blasts and initiate adaptive", "blasts and initiate adaptive immune", "and initiate adaptive immune responses.", "initiate adaptive immune responses. mhc", "adaptive immune responses. mhc class", "immune responses. mhc class ii", "responses. mhc class ii molecules", "mhc class ii molecules are", "class ii molecules are transmembrane", "ii molecules are transmembrane glycoprotein", "molecules are transmembrane glycoprotein heterodimers", "are transmembrane glycoprotein heterodimers of", "transmembrane glycoprotein heterodimers of alpha", "glycoprotein heterodimers of alpha and", "heterodimers of alpha and beta", "of alpha and beta subunits.", "alpha and beta subunits. newly", "and beta subunits. newly synthesized", "beta subunits. newly synthesized mhc", "subunits. newly synthesized mhc ii", "newly synthesized mhc ii molecules", "synthesized mhc ii molecules present", "mhc ii molecules present in", "ii molecules present in the", "molecules present in the endoplasmic", "present in the endoplasmic reticulum", "in the endoplasmic reticulum bind", "the endoplasmic reticulum bind to", "endoplasmic reticulum bind to a", "reticulum bind to a chaperone", "bind to a chaperone protein", "to a chaperone protein called", "a chaperone protein called invariant", "protein called invariant ii", "invariant ii chain.", "ii chain. the binding", "chain. the binding of ii", "the binding of ii prevents", "binding of ii prevents the", "of ii prevents the premature", "ii prevents the premature binding", "prevents the premature binding of", "the premature binding of self", "premature binding of self antigens", "binding of self antigens to", "of self antigens to the", "self antigens to the nascent", "antigens to the nascent mhc", "to the nascent mhc molecules", "the nascent mhc molecules in", "nascent mhc molecules in the", "mhc molecules in the er", "molecules in the er and", "in the er and also", "the er and also guides", "er and also guides mhc", "and also guides mhc molecules", "also guides mhc molecules to", "guides mhc molecules to endocytic", "mhc molecules to endocytic compartments.", "molecules to endocytic compartments. in", "to endocytic compartments. in the", "endocytic compartments. in the acidic", "compartments. in the acidic endosomal", "in the acidic endosomal environment", "acidic endosomal environment ii", "endosomal environment ii is", "environment ii is degraded", "ii is degraded in a", "is degraded in a stepwise", "degraded in a stepwise manner", "a stepwise manner ultimately", "stepwise manner ultimately to", "manner ultimately to free", "ultimately to free the class", "to free the class ii", "free the class ii peptide", "the class ii peptide binding", "class ii peptide binding groove", "ii peptide binding groove for", "peptide binding groove for loading", "binding groove for loading of", "groove for loading of antigenic", "for loading of antigenic peptides.", "loading of antigenic peptides. exogenous", "of antigenic peptides. exogenous antigens", "antigenic peptides. exogenous antigens are", "peptides. exogenous antigens are internalized", "exogenous antigens are internalized by", "antigens are internalized by the", "are internalized by the apc", "internalized by the apc by", "by the apc by receptor", "the apc by receptor mediated", "apc by receptor mediated endocytosis", "receptor mediated endocytosis phagocytosis", "mediated endocytosis phagocytosis or", "endocytosis phagocytosis or pinocytosis", "phagocytosis or pinocytosis into endocytic", "or pinocytosis into endocytic compartments", "pinocytosis into endocytic compartments of", "into endocytic compartments of mhc", "endocytic compartments of mhc class", "compartments of mhc class ii", "of mhc class ii positive", "mhc class ii positive cells", "ii positive cells where", "positive cells where engulfed", "cells where engulfed antigens", "where engulfed antigens are degraded", "engulfed antigens are degraded in", "antigens are degraded in a", "are degraded in a low", "degraded in a low ph", "in a low ph environment", "a low ph environment by", "low ph environment by multiple", "ph environment by multiple acidic", "environment by multiple acidic proteases", "multiple acidic proteases generating", "acidic proteases generating mhc", "proteases generating mhc class", "generating mhc class ii epitopes.", "mhc class ii epitopes. antigenic", "class ii epitopes. antigenic peptides", "ii epitopes. antigenic peptides are", "epitopes. antigenic peptides are then", "antigenic peptides are then loaded", "peptides are then loaded into", "are then loaded into the", "then loaded into the class", "loaded into the class ii", "into the class ii ligand", "the class ii ligand binding", "class ii ligand binding groove.", "ii ligand binding groove. the", "ligand binding groove. the resulting", "binding groove. the resulting class", "groove. the resulting class ii", "the resulting class ii peptide", "resulting class ii peptide complexes", "class ii peptide complexes then", "ii peptide complexes then move", "peptide complexes then move to", "complexes then move to the", "then move to the cell", "move to the cell surface", "the cell surface where", "cell surface where they", "surface where they are", "where they are scanned by", "they are scanned by cd4+", "are scanned by cd4+ t", "scanned by cd4+ t cells", "by cd4+ t cells for", "cd4+ t cells for specific", "t cells for specific recognition", "for specific recognition berger", "specific recognition berger &", "recognition berger & roche", "& roche 2009 zhou", "roche 2009 zhou &", "2009 zhou & blum", "& blum 2004 watts", "blum 2004 watts 2004", "watts 2004 landsverk et", "2004 landsverk et al.", "landsverk et al. 2009 ." ] }, { "record_id": "GLY_000594_1_216", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142753", "r hsa", "hsa 2142753", "r hsa 2142753" ] }, { "record_id": "GLY_000594_1_216", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "arachidonate metabolism", "20 carbon", "carbon fatty", "fatty acids", "are autocrine", "autocrine and", "and paracrine", "paracrine signaling", "signaling molecules", "molecules that", "that modulate", "modulate physiological", "physiological processes", "processes including", "including pain", "blood clot", "clot formation", "smooth muscle", "muscle contraction", "contraction and", "and relaxation", "and the", "the release", "release of", "of gastric", "gastric acid.", "acid. eicosanoids", "eicosanoids are", "synthesized in", "in humans", "humans primarily", "primarily from", "from arachidonate", "all cis", "cis 5", "5 8", "8 11", "11 14", "14 eicosatetraenoate", "that is", "is released", "released from", "from membrane", "membrane phospholipids.", "phospholipids. once", "once released", "arachidonate is", "is acted", "acted on", "on by", "by prostaglandin", "prostaglandin g/h", "g/h synthases", "also known", 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levels", "2008 .
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levels", "vance 2008 .
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levels of free", ".
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"1987 weigel & deangelis", "weigel & deangelis 2007", "& deangelis 2007 .", "deangelis 2007 . as", "2007 . as ha is", ". as ha is synthesised", "as ha is synthesised it", "ha is synthesised it is", "is synthesised it is extruded", "synthesised it is extruded from", "it is extruded from the", "is extruded from the cell", "extruded from the cell by", "from the cell by an", "the cell by an abc", "cell by an abc type", "by an abc type transporter", "an abc type transporter into", "abc type transporter into the", "type transporter into the extracellular", "transporter into the extracellular medium." ] }, { "record_id": "GLY_000594_1_219", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2151201", "r hsa", "hsa 2151201", "r hsa 2151201" ] }, { "record_id": "GLY_000594_1_219", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional activation", "activation of", "of mitochondrial", 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transcription", "and ppargc1a. transcription of ppargc1a", "ppargc1a. transcription of ppargc1a is", "transcription of ppargc1a is repressed", "of ppargc1a is repressed by", "ppargc1a is repressed by nr1d1", "repressed by nr1d1 rev", "by nr1d1 rev erba", "nr1d1 rev erba ." ] }, { "record_id": "GLY_000594_1_220", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "216083", "r hsa", "hsa 216083", "r hsa 216083" ] }, { "record_id": "GLY_000594_1_220", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "integrin cell", "cell surface", "surface interactions", "integrin cell surface", "cell surface interactions", "integrin cell surface interactions", "the extracellular", "extracellular matrix", "is a", "a network", "network of", "of macro", "macro molecules", "molecules that", "that underlies", "underlies all", "all epithelia", "epithelia and", "and endothelia", "endothelia and", "and that", "that 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integrins", "adhesive molecules.
integrins are", "molecules.
integrins are the", "are the receptors", "the receptors that", "receptors that mediate", "that mediate cell", "mediate cell adhesion", "cell adhesion to", "adhesion to ecm.", "to ecm. integrins", "ecm. integrins consists", "integrins consists of", "consists of one", "of one alpha", "one alpha and", "alpha and one", "and one beta", "one beta subunit", "beta subunit forming", "subunit forming a", "forming a noncovalently", "a noncovalently bound", "noncovalently bound heterodimer.", "bound heterodimer. 18", "heterodimer. 18 alpha", "18 alpha and", "alpha and 8", "and 8 beta", "8 beta subunits", "beta subunits have", "subunits have been", "have been identified", "been identified in", "identified in humans", "in humans that", "humans that combine", "that combine to", "combine to form", "to form 24", "form 24 different", "24 different receptors.", "different receptors.
the", "receptors.
the integrin", "
the integrin dimers", "integrin dimers can", "dimers can be", "can be broadly", "be broadly divided", "broadly divided into", "divided into three", "into three families", "three families consisting", "families consisting of", "consisting of the", "of the beta1", "beta1 beta2/beta7", "beta2/beta7 and", "and beta3/alphav integrins.", "beta3/alphav integrins. beta1", "integrins. beta1 associates", "beta1 associates with", "associates with 12", "with 12 alpha", "12 alpha subunits", "alpha subunits and", "subunits and can", "and can be", "can be further", "be further divided", "further divided into", "divided into rgd", "or laminin binding", "laminin binding and", "binding and the", "and the related", "the related alpha4/alpha9", "related alpha4/alpha9 integrins", "alpha4/alpha9 integrins that", "integrins that recognise", "that recognise both", "recognise both matrix", "both matrix and", "matrix and vascular", "and vascular ligands.", "vascular ligands. beta2/beta7", "ligands. beta2/beta7 integrins", "beta2/beta7 integrins are", "integrins are restricted", "are restricted to", "restricted to leukocytes", "to leukocytes and", "leukocytes and mediate", "and mediate cell", "mediate cell cell", "cell cell rather", "cell rather than", "rather than cell", "than cell matrix", "interactions although", "although some recognize", "some recognize fibrinogen.", "recognize fibrinogen. the", "fibrinogen. the beta3/alphav", "the beta3/alphav family", "beta3/alphav family members", "family members are", "members are all", "are all rgd", "all rgd receptors", "rgd receptors and", "receptors and comprise", "and comprise aiibb3", "aiibb3 an", "an important receptor", "important receptor on", "receptor on platelets", "platelets and", "and the remaining", "the remaining b", "remaining b subunits", "subunits which", "which all associate", "all associate with", "associate with alphav.", "with alphav. it", "alphav. it is", "it is the", "is the collagen", "the collagen receptors", "collagen receptors and", "receptors and leukocyte", "and leukocyte specific", "leukocyte specific integrins", "specific integrins that", "integrins that contain", "that contain alpha", "contain alpha a", "alpha a domains.", "extracellular matrix ecm", "ecm is a", "is a network of", "a network of macro", "network of macro molecules", "of macro molecules that", "macro molecules that underlies", "molecules that underlies all", "that underlies all epithelia", "underlies all epithelia and", "all epithelia and endothelia", "epithelia and endothelia and", "and endothelia and that", "endothelia and that surrounds", "and that surrounds all", "that surrounds all connective", "surrounds all connective tissue", "all connective tissue cells.", "connective tissue cells. this", "tissue cells. this matrix", "cells. this matrix provides", "this matrix provides the", "matrix provides the mechanical", "provides the mechanical strength", "the mechanical strength and", "mechanical strength and also", "strength and also influences", "and also influences the", "also influences the behavior", "influences the behavior and", "the behavior and differentiation", "behavior and differentiation state", "and differentiation state of", "differentiation state of cells", "state of cells in", "of cells in contact", "cells in contact with", "in contact with it.", "contact with it. the", "with it. the ecm", "it. the ecm are", "the ecm are diverse", "ecm are diverse in", "are diverse in composition", "in composition but", "composition but they", "but they generally comprise", "they generally comprise a", "generally comprise a mixture", "comprise a mixture of", "a mixture of fibrillar", "mixture of fibrillar proteins", "fibrillar proteins polysaccharides", "proteins polysaccharides synthesized", "polysaccharides synthesized secreted", "synthesized secreted and", "secreted and organized by", "and organized by neighboring", "organized by neighboring cells.", "by neighboring cells. collagens", "cells. collagens fibronectin", "fibronectin and laminins", "and laminins are the", "laminins are the principal", "are the principal components", "the principal components involved", "principal components involved in", "components involved in cell", "involved in cell matrix", "in cell matrix interactions", "matrix interactions other", "interactions other components", "other components such", "components such as", "as vitronectin thrombospondin", "thrombospondin and osteopontin", "and osteopontin although", "osteopontin although less", "less abundant are", "abundant are also", "are also important adhesive", "also important adhesive molecules.
integrins", "important adhesive molecules.
integrins are", "adhesive molecules.
integrins are the", "molecules.
integrins are the receptors", "are the receptors that", "the receptors that mediate", "receptors that mediate cell", "that mediate cell adhesion", "mediate cell adhesion to", "cell adhesion to ecm.", "adhesion to ecm. integrins", "to ecm. integrins consists", "ecm. integrins consists of", "integrins consists of one", "consists of one alpha", "of one alpha and", "one alpha and one", "alpha and one beta", "and one beta subunit", "one beta subunit forming", "beta subunit forming a", "subunit forming a noncovalently", "forming a noncovalently bound", "a noncovalently bound heterodimer.", "noncovalently bound heterodimer. 18", "bound heterodimer. 18 alpha", "heterodimer. 18 alpha and", "18 alpha and 8", "alpha and 8 beta", "and 8 beta subunits", "8 beta subunits have", "beta subunits have been", "subunits have been identified", "have been identified in", "been identified in humans", "identified in humans that", "in humans that combine", "humans that combine to", "that combine to form", "combine to form 24", "to form 24 different", "form 24 different receptors.", "24 different receptors.
the", "different receptors.
the integrin", "receptors.
the integrin dimers", "
the integrin dimers can", "integrin dimers can be", "dimers can be broadly", "can be broadly divided", "be broadly divided into", "broadly divided into three", "divided into three families", "into three families consisting", "three families consisting of", "families consisting of the", "consisting of the beta1", "the beta1 beta2/beta7", "beta2/beta7 and beta3/alphav", "and beta3/alphav integrins. beta1", "beta3/alphav integrins. beta1 associates", "integrins. beta1 associates with", "beta1 associates with 12", "associates with 12 alpha", "with 12 alpha subunits", "12 alpha subunits and", "alpha subunits and can", "subunits and can be", "and can be further", "can be further divided", "be further divided into", "further divided into rgd", "rgd collagen", "collagen or", "or laminin binding and", "laminin binding and the", "binding and the related", "and the related alpha4/alpha9", "the related alpha4/alpha9 integrins", "related alpha4/alpha9 integrins that", "alpha4/alpha9 integrins that recognise", "integrins that recognise both", "that recognise both matrix", "recognise both matrix and", "both matrix and vascular", "matrix and vascular ligands.", "and vascular ligands. beta2/beta7", "vascular ligands. beta2/beta7 integrins", "ligands. beta2/beta7 integrins are", "beta2/beta7 integrins are restricted", "integrins are restricted to", "are restricted to leukocytes", "restricted to leukocytes and", "to leukocytes and mediate", "leukocytes and mediate cell", "and mediate cell cell", "mediate cell cell rather", "cell cell rather than", "cell rather than cell", "rather than cell matrix", "than cell matrix interactions", "matrix interactions although", "interactions although some", "although some recognize fibrinogen.", "some recognize fibrinogen. the", "recognize fibrinogen. the beta3/alphav", "fibrinogen. the beta3/alphav family", "the beta3/alphav family members", "beta3/alphav family members are", "family members are all", "members are all rgd", "are all rgd receptors", "all rgd receptors and", "rgd receptors and comprise", "receptors and comprise aiibb3", "comprise aiibb3 an", "aiibb3 an important", "an important receptor on", "important receptor on platelets", "on platelets and", "platelets and the", "and the remaining b", "the remaining b subunits", "b subunits which", "subunits which all", "which all associate with", "all associate with alphav.", "associate with alphav. it", "with alphav. it is", "alphav. it is the", "it is the collagen", "is the collagen receptors", "the collagen receptors and", "collagen receptors and leukocyte", "receptors and leukocyte specific", "and leukocyte specific integrins", "leukocyte specific integrins that", "specific integrins that contain", "integrins that contain alpha", "that contain alpha a", "contain alpha a domains.", "the extracellular matrix ecm", "matrix ecm is", "ecm is a network", "is a network of macro", "a network of macro molecules", "network of macro molecules that", "of macro molecules that underlies", "macro molecules that underlies all", "molecules that underlies all epithelia", "that underlies all epithelia and", "underlies all epithelia and endothelia", "all epithelia and endothelia and", "epithelia and endothelia and that", "and endothelia and that surrounds", "endothelia and that surrounds all", "and that surrounds all connective", "that surrounds all connective tissue", "surrounds all connective tissue cells.", "all connective tissue cells. this", "connective tissue cells. this matrix", "tissue cells. this matrix provides", "cells. this matrix provides the", "this matrix provides the mechanical", "matrix provides the mechanical strength", "provides the mechanical strength and", "the mechanical strength and also", "mechanical strength and also influences", "strength and also influences the", "and also influences the behavior", "also influences the behavior and", "influences the behavior and differentiation", "the behavior and differentiation state", "behavior and differentiation state of", "and differentiation state of cells", "differentiation state of cells in", "state of cells in contact", "of cells in contact with", "cells in contact with it.", "in contact with it. the", "contact with it. the ecm", "with it. the ecm are", "it. the ecm are diverse", "the ecm are diverse in", "ecm are diverse in composition", "diverse in composition but", "in composition but they", "composition but they generally", "but they generally comprise a", "they generally comprise a mixture", "generally comprise a mixture of", "comprise a mixture of fibrillar", "a mixture of fibrillar proteins", "of fibrillar proteins polysaccharides", "fibrillar proteins polysaccharides synthesized", "polysaccharides synthesized secreted and", "synthesized secreted and organized", "secreted and organized by neighboring", "and organized by neighboring cells.", "organized by neighboring cells. collagens", "neighboring cells. collagens fibronectin", "collagens fibronectin and", "fibronectin and laminins are", "and laminins are the principal", "laminins are the principal components", "are the principal components involved", "the principal components involved in", "principal components involved in cell", "components involved in cell matrix", "involved in cell matrix interactions", "cell matrix interactions other", "matrix interactions other components", "other components such as", "components such as vitronectin", "such as vitronectin thrombospondin", "vitronectin thrombospondin and", "and osteopontin although less", "osteopontin although less abundant", "although less abundant are", "less abundant are also", "abundant are also important", "are also important adhesive molecules.
integrins", "also important adhesive molecules.
integrins are", "important adhesive molecules.
integrins are the", "adhesive molecules.
integrins are the receptors", "molecules.
integrins are the receptors that", "are the receptors that mediate", "the receptors that mediate cell", "receptors that mediate cell adhesion", "that mediate cell adhesion to", "mediate cell adhesion to ecm.", "cell adhesion to ecm. integrins", "adhesion to ecm. integrins consists", "to ecm. integrins consists of", "ecm. integrins consists of one", "integrins consists of one alpha", "consists of one alpha and", "of one alpha and one", "one alpha and one beta", "alpha and one beta subunit", "and one beta subunit forming", "one beta subunit forming a", "beta subunit forming a noncovalently", "subunit forming a noncovalently bound", "forming a noncovalently bound heterodimer.", "a noncovalently bound heterodimer. 18", "noncovalently bound heterodimer. 18 alpha", "bound heterodimer. 18 alpha and", "heterodimer. 18 alpha and 8", "18 alpha and 8 beta", "alpha and 8 beta subunits", "and 8 beta subunits have", "8 beta subunits have been", "beta subunits have been identified", "subunits have been identified in", "have been identified in humans", "been identified in humans that", "identified in humans that combine", "in humans that combine to", "humans that combine to form", "that combine to form 24", "combine to form 24 different", "to form 24 different receptors.", "form 24 different receptors.
the", "24 different receptors.
the integrin", "different receptors.
the integrin dimers", "receptors.
the integrin dimers can", "
the integrin dimers can be", "integrin dimers can be broadly", "dimers can be broadly divided", "can be broadly divided into", "be broadly divided into three", "broadly divided into three families", "divided into three families consisting", "into three families consisting of", "three families consisting of the", "families consisting of the beta1", "of the beta1 beta2/beta7", "beta1 beta2/beta7 and", "beta2/beta7 and beta3/alphav integrins.", "and beta3/alphav integrins. beta1 associates", "beta3/alphav integrins. beta1 associates with", "integrins. beta1 associates with 12", "beta1 associates with 12 alpha", "associates with 12 alpha subunits", "with 12 alpha subunits and", "12 alpha subunits and can", "alpha subunits and can be", "subunits and can be further", "and can be further divided", "can be further divided into", "be further divided into rgd", "into rgd collagen", "collagen or laminin", "or laminin binding and the", "laminin binding and the related", "binding and the related alpha4/alpha9", "and the related alpha4/alpha9 integrins", "the related alpha4/alpha9 integrins that", "related alpha4/alpha9 integrins that recognise", "alpha4/alpha9 integrins that recognise both", "integrins that recognise both matrix", "that recognise both matrix and", "recognise both matrix and vascular", "both matrix and vascular ligands.", "matrix and vascular ligands. beta2/beta7", "and vascular ligands. beta2/beta7 integrins", "vascular ligands. beta2/beta7 integrins are", "ligands. beta2/beta7 integrins are restricted", "beta2/beta7 integrins are restricted to", "integrins are restricted to leukocytes", "are restricted to leukocytes and", "restricted to leukocytes and mediate", "to leukocytes and mediate cell", "leukocytes and mediate cell cell", "and mediate cell cell rather", "mediate cell cell rather than", "cell cell rather than cell", "cell rather than cell matrix", "rather than cell matrix interactions", "cell matrix interactions although", "matrix interactions although some", "interactions although some recognize", "although some recognize fibrinogen. the", "some recognize fibrinogen. the beta3/alphav", "recognize fibrinogen. the beta3/alphav family", "fibrinogen. the beta3/alphav family members", "the beta3/alphav family members are", "beta3/alphav family members are all", "family members are all rgd", "members are all rgd receptors", "are all rgd receptors and", "all rgd receptors and comprise", "rgd receptors and comprise aiibb3", "and comprise aiibb3 an", "comprise aiibb3 an important", "aiibb3 an important receptor", "an important receptor on platelets", "receptor on platelets and", "on platelets and the", "platelets and the remaining", "and the remaining b subunits", "remaining b subunits which", "b subunits which all", "subunits which all associate", "which all associate with alphav.", "all associate with alphav. it", "associate with alphav. it is", "with alphav. it is the", "alphav. it is the collagen", "it is the collagen receptors", "is the collagen receptors and", "the collagen receptors and leukocyte", "collagen receptors and leukocyte specific", "receptors and leukocyte specific integrins", "and leukocyte specific integrins that", "leukocyte specific integrins that contain", "specific integrins that contain alpha", "integrins that contain alpha a", "that contain alpha a domains." ] }, { "record_id": "GLY_000594_1_221", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2161517", "r hsa", "hsa 2161517", "r hsa 2161517" ] }, { "record_id": "GLY_000594_1_221", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "abacavir transmembrane", "transmembrane transport", "abacavir transmembrane transport", "cytosolic levels", "levels of", "of abacavir", "abacavir are", "are determined", "determined by", "by the", "the balance", "balance of", "of its", "its facilitated", "facilitated diffusion", "diffusion into", "into the", "the cell", "cell 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thromboxanes tx", "synthesis of prostaglandins pg", "prostaglandins pg and", "the bioactive", "bioactive prostaglandin", "signalling molecules", "including pga2", "and pgi2", "are synthesised", "synthesised from", "from arachidonate", "arachidonate and", "and its", "its products", "products by", "by various", "various prostaglandin", "prostaglandin synthase", "synthase type", "type enzymes.", "enzymes. prostaglandin", "prostaglandin h2", "is the", "the starting", "starting point", "point for", "for the", "the synthesis", "of thromboxanes", "buczynski et", "et al.", "al. 2009", "vance &", "& vance", "vance 2008", "2008 .", ". pgs", "pgs and", "and txs", "txs are", "are collectively", "collectively known", "known as", "as the", "the prostanoids.
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molecule", "adapter molecule that", "molecule that transduces", "that transduces activating", "transduces activating signals", "activating signals in", "signals in natural", "in natural killer", "killer nk", "nk and", "and myeloid cells.", "myeloid cells. it", "cells. it mediates", "it mediates signalling", "mediates signalling for", "signalling for multiple", "for multiple cell", "multiple cell surface", "cell surface receptors", "surface receptors expressed", "receptors expressed by", "expressed by these", "by these cells", "cells associating", "associating with receptor", "with receptor chains", "receptor chains through", "chains through complementary", "through complementary charged", "complementary charged transmembrane", "charged transmembrane amino", "transmembrane amino acids", "amino acids that", "acids that form", "that form a", "form a salt", "a salt bridge", "salt bridge in", "bridge in the", "in the context", "the context of", "context of the", "of the hydrophobic", "the hydrophobic lipid", "hydrophobic lipid bilayer", "bilayer lanier", "lanier et al.", "et al. 1998", "al. 1998 .", "1998 . dap12", ". dap12 homodimers", "dap12 homodimers associate", "homodimers associate with", "associate with a", "with a variety", "a variety of", "variety of receptors", "of receptors expressed", "expressed by macrophages", "macrophages monocytes", "monocytes and myeloid", "and myeloid cells", "myeloid cells including", "cells including trem2", "trem2 siglec", "siglec h and", "h and sirp", "and sirp beta", "beta as", "as well as", "well as activating", "as activating kir", "kir ly49", "ly49 and the", "and the nkg2c", "the nkg2c proteins", "nkg2c proteins expressed", "proteins expressed by", "expressed by nk", "by nk cells.", "nk cells. dap12", "cells. dap12 is", "dap12 is expressed", "is expressed at", "expressed at the", "at the cell", "the cell surface", "surface with", "with most of", "most of the", "of the protein", "the protein lying", "protein lying on", "lying on the", "on the cytoplasmic", "the cytoplasmic side", "cytoplasmic side of", "side of the", "of the membrane", "membrane turnbull", "turnbull & colonna", "& colonna 2007", "2007 tessarz", "tessarz & cerwenka", "& cerwenka 2008", "cerwenka 2008 .", "dnax activation protein of", "activation protein of 12kda", "of 12kda dap12", "dap12 is an", "is an immunoreceptor tyrosine", "an immunoreceptor tyrosine based", "immunoreceptor tyrosine based activation", "tyrosine based activation motif", "activation motif itam", "itam bearing adapter", "bearing adapter molecule that", "adapter molecule that transduces", "molecule that transduces activating", "that transduces activating signals", "transduces activating signals in", "activating signals in natural", "signals in natural killer", "natural killer nk", "nk and myeloid", "and myeloid cells. it", "myeloid cells. it mediates", "cells. it mediates signalling", "it mediates signalling for", "mediates signalling for multiple", "signalling for multiple cell", "for multiple cell surface", "multiple cell surface receptors", "cell surface receptors expressed", "surface receptors expressed by", "receptors expressed by these", "expressed by these cells", "these cells associating", "cells associating with", "associating with receptor chains", "with receptor chains through", "receptor chains through complementary", "chains through complementary charged", "through complementary charged transmembrane", "complementary charged transmembrane amino", "charged transmembrane amino acids", "transmembrane amino acids that", "amino acids that form", "acids that form a", "that form a salt", "form a salt bridge", "a salt bridge in", "salt bridge in the", "bridge in the context", "in the context of", "the context of the", "context of the hydrophobic", "of the hydrophobic lipid", "the hydrophobic lipid bilayer", "lipid bilayer lanier", "bilayer lanier et", "lanier et al. 1998", "et al. 1998 .", "al. 1998 . dap12", "1998 . dap12 homodimers", ". dap12 homodimers associate", "dap12 homodimers associate with", "homodimers associate with a", "associate with a variety", "with a variety of", "a variety of receptors", "variety of receptors expressed", "of receptors expressed by", "receptors expressed by macrophages", "by macrophages monocytes", "macrophages monocytes and", "monocytes and myeloid cells", "and myeloid cells including", "myeloid cells including trem2", "including trem2 siglec", "trem2 siglec h", "siglec h and sirp", "h and sirp beta", "sirp beta as", "beta as well", "as well as activating", "well as activating kir", "activating kir ly49", "kir ly49 and", "ly49 and the nkg2c", "and the nkg2c proteins", "the nkg2c proteins expressed", "nkg2c proteins expressed by", "proteins expressed by nk", "expressed by nk cells.", "by nk cells. dap12", "nk cells. dap12 is", "cells. dap12 is expressed", "dap12 is expressed at", "is expressed at the", "expressed at the cell", "at the cell surface", "cell surface with", "surface with most", "with most of the", "most of the protein", "of the protein lying", "the protein lying on", "protein lying on the", "lying on the cytoplasmic", "on the cytoplasmic side", "the cytoplasmic side of", "cytoplasmic side of the", "side of the membrane", "the membrane turnbull", "membrane turnbull &", "turnbull & colonna 2007", "colonna 2007 tessarz", "2007 tessarz &", "tessarz & cerwenka 2008", "& cerwenka 2008 .", "dnax activation protein of 12kda", "protein of 12kda dap12", "12kda dap12 is", "dap12 is an immunoreceptor", "is an immunoreceptor tyrosine based", "an immunoreceptor tyrosine based activation", "immunoreceptor tyrosine based activation motif", "based activation motif itam", "motif itam bearing", "itam bearing adapter molecule", "bearing adapter molecule that transduces", "adapter molecule that transduces activating", "molecule that transduces activating signals", "that transduces activating signals in", "transduces activating signals in natural", "activating signals in natural killer", "in natural killer nk", "killer nk and", "nk and myeloid cells.", "and myeloid cells. it mediates", "myeloid cells. it mediates signalling", "cells. it mediates signalling for", "it mediates signalling for multiple", "mediates signalling for multiple cell", "signalling for multiple cell surface", "for multiple cell surface receptors", "multiple cell surface receptors expressed", "cell surface receptors expressed by", "surface receptors expressed by these", "receptors expressed by these cells", "by these cells associating", "these cells associating with", "cells associating with receptor", "associating with receptor chains through", "with receptor chains through complementary", "receptor chains through complementary charged", "chains through complementary charged transmembrane", "through complementary charged transmembrane amino", "complementary charged transmembrane amino acids", "charged transmembrane amino acids that", "transmembrane amino acids that form", "amino acids that form a", "acids that form a salt", "that form a salt bridge", "form a salt bridge in", "a salt bridge in the", "salt bridge in the context", "bridge in the context of", "in the context of the", "the context of the hydrophobic", "context of the hydrophobic lipid", "of the hydrophobic lipid bilayer", "hydrophobic lipid bilayer lanier", "lipid bilayer lanier et", "bilayer lanier et al.", "lanier et al. 1998 .", "et al. 1998 . dap12", "al. 1998 . dap12 homodimers", "1998 . dap12 homodimers associate", ". dap12 homodimers associate with", "dap12 homodimers associate with a", "homodimers associate with a variety", "associate with a variety of", "with a variety of receptors", "a variety of receptors expressed", "variety of receptors expressed by", "of receptors expressed by macrophages", "expressed by macrophages monocytes", "by macrophages monocytes and", "macrophages monocytes and myeloid", "monocytes and myeloid cells including", "and myeloid cells including trem2", "cells including trem2 siglec", "including trem2 siglec h", "trem2 siglec h and", "siglec h and sirp beta", "and sirp beta as", "sirp beta as well", "beta as well as", "as well as activating kir", "as activating kir ly49", "activating kir ly49 and", "kir ly49 and the", "ly49 and the nkg2c proteins", "and the nkg2c proteins expressed", "the nkg2c proteins expressed by", "nkg2c proteins expressed by nk", "proteins expressed by nk cells.", "expressed by nk cells. dap12", "by nk cells. dap12 is", "nk cells. dap12 is expressed", "cells. dap12 is expressed at", "dap12 is expressed at the", "is expressed at the cell", "expressed at the cell surface", "the cell surface with", "cell surface with most", "surface with most of", "with most of the protein", "most of the protein lying", "of the protein lying on", "the protein lying on the", "protein lying on the cytoplasmic", "lying on the cytoplasmic side", "on the cytoplasmic side of", "the cytoplasmic side of the", "cytoplasmic side of the membrane", "of the membrane turnbull", "the membrane turnbull &", "membrane turnbull & colonna", "& colonna 2007 tessarz", "colonna 2007 tessarz &", "2007 tessarz & cerwenka", "tessarz & cerwenka 2008 ." ] }, { "record_id": "GLY_000594_1_225", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2173788", "r hsa", "hsa 2173788", "r hsa 2173788" ] }, { "record_id": "GLY_000594_1_225", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "downregulation of", "of tgf", "tgf beta", "beta receptor", "receptor signaling", "downregulation of tgf", "of tgf beta", "tgf beta receptor", "beta receptor signaling", "downregulation of tgf beta", "of tgf beta receptor", "tgf beta receptor signaling", "downregulation of tgf beta receptor", "of tgf beta receptor signaling", "signaling is", "is downregulated", "downregulated by", "by proteasome", "proteasome and", "and lysosome", "lysosome mediated", "mediated degradation", "degradation of", "of ubiquitinated", "ubiquitinated tgfbr1", "smad2 and", "and smad3", "as well", "well as", "as by", "by dephosphorylation", "dephosphorylation of", "of tgfbr1", "and smad3.", "smad3.

in", "

in the", "the nucleus", "smad2/3:smad4 complex", "complex stimulates", "stimulates transcription", "transcription of", "of smad7", "an inhibitory", "inhibitory smad", "i smad", "smad .", ". smad7", "smad7 binds", "binds phosphorylated", "phosphorylated tgfbr1", "tgfbr1 and", "and competes", "competes with", "with the", "the binding", "binding of", "of smad2", "hayashi et", "et al.", "al. 1997", "nakao et", "1997 .", ". binding", "smad7 to", "to tgbr1", "tgbr1 can", "can be", "be stabilized", "stabilized by", "by strap", "a protein", "protein that", "that simultaneously", "simultaneously binds", "binds smad7", "smad7 and", "and tgfbr1", "datta et", "al. 2000", "2000 .", ". bambi", "bambi simultaneously", "and activated", "activated tgfbr1", "leading to", "to downregulation", "receptor complex", "complex signaling", "onichtchouk et", "al. 1999", "yan et", "al. 2009", "2009 .
", ".

in", "
in addition", "addition to", "to competing", "competing with", "with smad2/3", "smad2/3 binding", "binding to", "to tgfbr1", "smad7 recruits", "recruits protein", "protein phosphatase", "phosphatase pp1", "pp1 to", "to phosphorylated", "by binding", "to the", "the pp1", "pp1 regulatory", "regulatory subunit", "subunit ppp1r15a", "gadd34 .", ". pp1", "pp1 dephosphorylates", "dephosphorylates tgfbr1", "preventing the", "the activation", "activation of", "of smad2/3", "smad2/3 and", "and propagation", "propagation of", "beta signal", "shi et", "al. 2004", "2004 .", ".
", "

smad7", "
smad7 associates", "associates with", "with several", "several ubiquitin", "ubiquitin ligases", "ebisawa et", "al. 2001", "suzuki et", "al. 2002", "tajima et", "al. 2003", "chong et", "al. 2010", "kavsak et", "ogunjimi et", "al. 2005", "and nedd4l", "kuratomi et", "and recruits", "recruits them", "them to", "tgfbr1 within", "within tgfbr", "tgfbr complex.", "complex. smurf1", "smurf2 and", "nedd4l ubiquitinate", "ubiquitinate tgfbr1", "and smad7", "targeting tgfbr", "tgfbr complex", "complex for", "for proteasome", "lysosome dependent", "dependent degradation", "2005 .", ". the", "the ubiquitination", "ubiquitination of", "tgfbr1 can", "be reversed", "reversed by", "by deubiquitinating", "deubiquitinating enzymes", "and usp15", "which may", "may be", "be recruited", "recruited to", "to ubiquitinated", "tgfbr1 by", "by smad7", "wicks et", "eichhorn et", "al. 2012", "2012 .", "

basal", "
basal levels", "levels of", "smad3 are", "are maintained", "maintained by", "by smurf2", "and stub1", "stub1 ubiquitin", "ubiquitin ligases.", "ligases. smurf2", "smurf2 is", "is able", "able to", "to bind", "bind and", "and ubiquitinate", "ubiquitinate smad2", "to smad2", "smad2 degradation", "zhang et", "but this", "this has", "has been", "been questioned", "questioned by", "by a", "a recent", "recent study", "study of", "of smurf2", "smurf2 knockout", "knockout mice", "tang et", "al. 2011", "2011 .", ". stub1", "binds and", "and ubiquitinates", "ubiquitinates smad3", "to smad3", "smad3 degradation", "li et", "xin et", ". pmepa1", "pmepa1 can", "can bind", "and sequester", "sequester unphosphorylated", "unphosphorylated smad2", "preventing their", "their activation", "activation in", "in response", "response to", "to tgf", "beta signaling.", "signaling. in", "in addition", "sequester phosphorylated", "phosphorylated smad2", "preventing formation", "formation of", "of smad2/3:smad4", "smad2/3:smad4 heterotrimer", "heterotrimer complexes", "watanabe et", "2010 .", ". a", "phosphatase mtmr4", "residing in", "in the", "the membrane", "membrane of", "of early", "early endosomes", "can dephosphorylate", "dephosphorylate activated", "activated smad2", "smad2/3:smad4 complexes", "yu et", "receptor signaling is", "signaling is downregulated", "is downregulated by", "downregulated by proteasome", "by proteasome and", "proteasome and lysosome", "and lysosome mediated", "lysosome mediated degradation", "mediated degradation of", "degradation of ubiquitinated", "of ubiquitinated tgfbr1", "tgfbr1 smad2", "smad2 and smad3", "smad3 as", "as well as", "well as by", "as by dephosphorylation", "by dephosphorylation of", "dephosphorylation of tgfbr1", "smad2 and smad3.", "and smad3.

in", "smad3.

in the", "

in the nucleus", "nucleus smad2/3:smad4", "smad2/3:smad4 complex stimulates", "complex stimulates transcription", "stimulates transcription of", "transcription of smad7", "smad7 an", "an inhibitory smad", "smad i", "i smad .", "smad . smad7", ". smad7 binds", "smad7 binds phosphorylated", "binds phosphorylated tgfbr1", "phosphorylated tgfbr1 and", "tgfbr1 and competes", "and competes with", "competes with the", "with the binding", "the binding of", "binding of smad2", "of smad2 and", "smad3 hayashi", "hayashi et al.", "et al. 1997", "1997 nakao", "nakao et al.", "al. 1997 .", "1997 . binding", ". binding of", "binding of smad7", "of smad7 to", "smad7 to tgbr1", "to tgbr1 can", "tgbr1 can be", "can be stabilized", "be stabilized by", "stabilized by strap", "strap a", "a protein that", "protein that simultaneously", "that simultaneously binds", "simultaneously binds smad7", "binds smad7 and", "smad7 and tgfbr1", "tgfbr1 datta", "datta et al.", "et al. 2000", "al. 2000 .", "2000 . bambi", ". bambi simultaneously", "bambi simultaneously binds", "smad7 and activated", "and activated tgfbr1", "tgfbr1 leading", "leading to downregulation", "to downregulation of", "beta receptor complex", "receptor complex signaling", "signaling onichtchouk", "onichtchouk et al.", "et al. 1999", "1999 yan", "yan et al.", "et al. 2009", "al. 2009 .
", "2009 .

in", ".

in addition", "
in addition to", "addition to competing", "to competing with", "competing with smad2/3", "with smad2/3 binding", "smad2/3 binding to", "binding to tgfbr1", "tgfbr1 smad7", "smad7 recruits protein", "recruits protein phosphatase", "protein phosphatase pp1", "phosphatase pp1 to", "pp1 to phosphorylated", "to phosphorylated tgfbr1", "by binding to", "binding to the", "to the pp1", "the pp1 regulatory", "pp1 regulatory subunit", "regulatory subunit ppp1r15a", "ppp1r15a gadd34", "gadd34 . pp1", ". pp1 dephosphorylates", "pp1 dephosphorylates tgfbr1", "tgfbr1 preventing", "preventing the activation", "the activation of", "activation of smad2/3", "of smad2/3 and", "smad2/3 and propagation", "and propagation of", "propagation of tgf", "tgf beta signal", "signal shi", "shi et al.", "et al. 2004", "al. 2004 .", "2004 .
", ".

smad7", "

smad7 associates", "
smad7 associates with", "associates with several", "with several ubiquitin", "several ubiquitin ligases", "ligases smurf1", "smurf1 ebisawa", "ebisawa et al.", "et al. 2001", "2001 suzuki", "suzuki et al.", "et al. 2002", "2002 tajima", "tajima et al.", "et al. 2003", "2003 chong", "chong et al.", "et al. 2010", "smurf2 kavsak", "kavsak et al.", "2000 ogunjimi", "ogunjimi et al.", "et al. 2005", "nedd4l kuratomi", "kuratomi et al.", "and recruits them", "recruits them to", "them to phosphorylated", "phosphorylated tgfbr1 within", "tgfbr1 within tgfbr", "within tgfbr complex.", "tgfbr complex. smurf1", "smurf1 smurf2", "smurf2 and nedd4l", "and nedd4l ubiquitinate", "nedd4l ubiquitinate tgfbr1", "targeting tgfbr complex", "tgfbr complex for", "complex for proteasome", "for proteasome and", "and lysosome dependent", "lysosome dependent degradation", "degradation ebisawa", "2001 kavsak", "2000 kuratomi", "al. 2005 .", "2005 . the", ". the ubiquitination", "the ubiquitination of", "ubiquitination of tgfbr1", "of tgfbr1 can", "tgfbr1 can be", "can be reversed", "be reversed by", "reversed by deubiquitinating", "by deubiquitinating enzymes", "enzymes uchl5", "uchl5 uch37", "uch37 and", "usp15 which", "which may be", "may be recruited", "be recruited to", "recruited to ubiquitinated", "to ubiquitinated tgfbr1", "ubiquitinated tgfbr1 by", "tgfbr1 by smad7", "smad7 wicks", "wicks et al.", "2005 eichhorn", "eichhorn et al.", "et al. 2012", "al. 2012 .", "2012 .
", ".

basal", "

basal levels", "
basal levels of", "levels of smad2", "and smad3 are", "smad3 are maintained", "are maintained by", "maintained by smurf2", "by smurf2 and", "smurf2 and stub1", "and stub1 ubiquitin", "stub1 ubiquitin ligases.", "ubiquitin ligases. smurf2", "ligases. smurf2 is", "smurf2 is able", "is able to", "able to bind", "to bind and", "bind and ubiquitinate", "and ubiquitinate smad2", "smad2 leading", "leading to smad2", "to smad2 degradation", "degradation zhang", "zhang et al.", "but this has", "this has been", "has been questioned", "been questioned by", "questioned by a", "by a recent", "a recent study", "recent study of", "study of smurf2", "of smurf2 knockout", "smurf2 knockout mice", "mice tang", "tang et al.", "et al. 2011", "al. 2011 .", "2011 . stub1", "stub1 chip", "chip binds", "binds and ubiquitinates", "and ubiquitinates smad3", "smad3 leading", "leading to smad3", "to smad3 degradation", "degradation li", "li et al.", "2004 xin", "xin et al.", "2005 . pmepa1", ". pmepa1 can", "pmepa1 can bind", "can bind and", "bind and sequester", "and sequester unphosphorylated", "sequester unphosphorylated smad2", "unphosphorylated smad2 and", "smad3 preventing", "preventing their activation", "their activation in", "activation in response", "in response to", "response to tgf", "to tgf beta", "tgf beta signaling.", "beta signaling. in", "signaling. in addition", "addition pmepa1", "and sequester phosphorylated", "sequester phosphorylated smad2", "phosphorylated smad2 and", "preventing formation of", "formation of smad2/3:smad4", "of smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer complexes", "complexes watanabe", "watanabe et al.", "al. 2010 .", "2010 . a", ". a protein", "a protein phosphatase", "protein phosphatase mtmr4", "mtmr4 residing", "residing in the", "in the membrane", "the membrane of", "membrane of early", "of early endosomes", "endosomes can", "can dephosphorylate activated", "dephosphorylate activated smad2", "activated smad2 and", "of smad2/3:smad4 complexes", "complexes yu", "yu et al.", "2010 .
", "beta receptor signaling is", "receptor signaling is downregulated", "signaling is downregulated by", "is downregulated by proteasome", "downregulated by proteasome and", "by proteasome and lysosome", "proteasome and lysosome mediated", "and lysosome mediated degradation", "lysosome mediated degradation of", "mediated degradation of ubiquitinated", "degradation of ubiquitinated tgfbr1", "ubiquitinated tgfbr1 smad2", "tgfbr1 smad2 and", "and smad3 as", "smad3 as well", "as well as by", "well as by dephosphorylation", "as by dephosphorylation of", "by dephosphorylation of tgfbr1", "of tgfbr1 smad2", "smad2 and smad3.

in", "and smad3.

in the", "smad3.

in the nucleus", "the nucleus smad2/3:smad4", "nucleus smad2/3:smad4 complex", "smad2/3:smad4 complex stimulates transcription", "complex stimulates transcription of", "stimulates transcription of smad7", "of smad7 an", "smad7 an inhibitory", "inhibitory smad i", "smad i smad", "i smad . smad7", "smad . smad7 binds", ". smad7 binds phosphorylated", "smad7 binds phosphorylated tgfbr1", "binds phosphorylated tgfbr1 and", "phosphorylated tgfbr1 and competes", "tgfbr1 and competes with", "and competes with the", "competes with the binding", "with the binding of", "the binding of smad2", "binding of smad2 and", "of smad2 and smad3", "and smad3 hayashi", "smad3 hayashi et", "hayashi et al. 1997", "al. 1997 nakao", "1997 nakao et", "nakao et al. 1997", "et al. 1997 .", "al. 1997 . binding", "1997 . binding of", ". binding of smad7", "binding of smad7 to", "of smad7 to tgbr1", "smad7 to tgbr1 can", "to tgbr1 can be", "tgbr1 can be stabilized", "can be stabilized by", "be stabilized by strap", "by strap a", "strap a protein", "a protein that simultaneously", "protein that simultaneously binds", "that simultaneously binds smad7", "simultaneously binds smad7 and", "binds smad7 and tgfbr1", "and tgfbr1 datta", "tgfbr1 datta et", "datta et al. 2000", "et al. 2000 .", "al. 2000 . bambi", "2000 . bambi simultaneously", ". bambi simultaneously binds", "bambi simultaneously binds smad7", "binds smad7 and activated", "smad7 and activated tgfbr1", "activated tgfbr1 leading", "tgfbr1 leading to", "leading to downregulation of", "to downregulation of tgf", "tgf beta receptor complex", "beta receptor complex signaling", "complex signaling onichtchouk", "signaling onichtchouk et", "onichtchouk et al. 1999", "al. 1999 yan", "1999 yan et", "yan et al. 2009", "et al. 2009 .
", "al. 2009 .

in", "2009 .

in addition", ".

in addition to", "
in addition to competing", "addition to competing with", "to competing with smad2/3", "competing with smad2/3 binding", "with smad2/3 binding to", "smad2/3 binding to tgfbr1", "to tgfbr1 smad7", "tgfbr1 smad7 recruits", "smad7 recruits protein phosphatase", "recruits protein phosphatase pp1", "protein phosphatase pp1 to", "phosphatase pp1 to phosphorylated", "pp1 to phosphorylated tgfbr1", "phosphorylated tgfbr1 by", "tgfbr1 by binding", "by binding to the", "binding to the pp1", "to the pp1 regulatory", "the pp1 regulatory subunit", "pp1 regulatory subunit ppp1r15a", "subunit ppp1r15a gadd34", "ppp1r15a gadd34 .", "gadd34 . pp1 dephosphorylates", ". pp1 dephosphorylates tgfbr1", "dephosphorylates tgfbr1 preventing", "tgfbr1 preventing the", "preventing the activation of", "the activation of smad2/3", "activation of smad2/3 and", "of smad2/3 and propagation", "smad2/3 and propagation of", "and propagation of tgf", "propagation of tgf beta", "of tgf beta signal", "beta signal shi", "signal shi et", "shi et al. 2004", "et al. 2004 .", "al. 2004 .
", "2004 .

smad7", ".

smad7 associates", "

smad7 associates with", "
smad7 associates with several", "associates with several ubiquitin", "with several ubiquitin ligases", "ubiquitin ligases smurf1", "smurf1 ebisawa et", "ebisawa et al. 2001", "al. 2001 suzuki", "2001 suzuki et", "suzuki et al. 2002", "al. 2002 tajima", "2002 tajima et", "tajima et al. 2003", "al. 2003 chong", "2003 chong et", "chong et al. 2010", "2010 smurf2", "smurf2 kavsak et", "kavsak et al. 2000", "al. 2000 ogunjimi", "2000 ogunjimi et", "ogunjimi et al. 2005", "2005 and", "and nedd4l kuratomi", "nedd4l kuratomi et", "kuratomi et al. 2005", "and recruits them to", "recruits them to phosphorylated", "them to phosphorylated tgfbr1", "to phosphorylated tgfbr1 within", "phosphorylated tgfbr1 within tgfbr", "tgfbr1 within tgfbr complex.", "within tgfbr complex. smurf1", "complex. smurf1 smurf2", "smurf1 smurf2 and", "smurf2 and nedd4l ubiquitinate", "and nedd4l ubiquitinate tgfbr1", "ubiquitinate tgfbr1 and", "tgfbr1 and smad7", "smad7 targeting", "targeting tgfbr complex for", "tgfbr complex for proteasome", "complex for proteasome and", "for proteasome and lysosome", "proteasome and lysosome dependent", "and lysosome dependent degradation", "dependent degradation ebisawa", "degradation ebisawa et", "al. 2001 kavsak", "2001 kavsak et", "al. 2000 kuratomi", "2000 kuratomi et", "et al. 2005 .", "al. 2005 . the", "2005 . the ubiquitination", ". the ubiquitination of", "the ubiquitination of tgfbr1", "ubiquitination of tgfbr1 can", "of tgfbr1 can be", "tgfbr1 can be reversed", "can be reversed by", "be reversed by deubiquitinating", "reversed by deubiquitinating enzymes", "deubiquitinating enzymes uchl5", "uch37 and usp15", "and usp15 which", "usp15 which may", "which may be recruited", "may be recruited to", "be recruited to ubiquitinated", "recruited to ubiquitinated tgfbr1", "to ubiquitinated tgfbr1 by", "ubiquitinated tgfbr1 by smad7", "by smad7 wicks", "smad7 wicks et", "wicks et al. 2005", "al. 2005 eichhorn", "2005 eichhorn et", "eichhorn et al. 2012", "et al. 2012 .", "al. 2012 .
", "2012 .

basal", ".

basal levels", "

basal levels of", "
basal levels of smad2", "levels of smad2 and", "smad2 and smad3 are", "and smad3 are maintained", "smad3 are maintained by", "are maintained by smurf2", "maintained by smurf2 and", "by smurf2 and stub1", "smurf2 and stub1 ubiquitin", "and stub1 ubiquitin ligases.", "stub1 ubiquitin ligases. smurf2", "ubiquitin ligases. smurf2 is", "ligases. smurf2 is able", "smurf2 is able to", "is able to bind", "able to bind and", "to bind and ubiquitinate", "bind and ubiquitinate smad2", "ubiquitinate smad2 leading", "smad2 leading to", "leading to smad2 degradation", "smad2 degradation zhang", "degradation zhang et", "zhang et al. 2001", "2001 but", "but this has been", "this has been questioned", "has been questioned by", "been questioned by a", "questioned by a recent", "by a recent study", "a recent study of", "recent study of smurf2", "study of smurf2 knockout", "of smurf2 knockout mice", "knockout mice tang", "mice tang et", "tang et al. 2011", "et al. 2011 .", "al. 2011 . stub1", ". stub1 chip", "chip binds and", "binds and ubiquitinates smad3", "ubiquitinates smad3 leading", "smad3 leading to", "leading to smad3 degradation", "smad3 degradation li", "degradation li et", "li et al. 2004", "al. 2004 xin", "2004 xin et", "xin et al. 2005", "al. 2005 . pmepa1", "2005 . pmepa1 can", ". pmepa1 can bind", "pmepa1 can bind and", "can bind and sequester", "bind and sequester unphosphorylated", "and sequester unphosphorylated smad2", "sequester unphosphorylated smad2 and", "unphosphorylated smad2 and smad3", "and smad3 preventing", "smad3 preventing their", "preventing their activation in", "their activation in response", "activation in response to", "in response to tgf", "response to tgf beta", "to tgf beta signaling.", "tgf beta signaling. in", "beta signaling. in addition", "in addition pmepa1", "addition pmepa1 can", "bind and sequester phosphorylated", "and sequester phosphorylated smad2", "sequester phosphorylated smad2 and", "phosphorylated smad2 and smad3", "smad3 preventing formation", "preventing formation of smad2/3:smad4", "formation of smad2/3:smad4 heterotrimer", "of smad2/3:smad4 heterotrimer complexes", "heterotrimer complexes watanabe", "complexes watanabe et", "watanabe et al. 2010", "et al. 2010 .", "al. 2010 . a", "2010 . a protein", ". a protein phosphatase", "a protein phosphatase mtmr4", "phosphatase mtmr4 residing", "mtmr4 residing in", "residing in the membrane", "in the membrane of", "the membrane of early", "membrane of early endosomes", "early endosomes can", "endosomes can dephosphorylate", "can dephosphorylate activated smad2", "dephosphorylate activated smad2 and", "activated smad2 and smad3", "formation of smad2/3:smad4 complexes", "smad2/3:smad4 complexes yu", "complexes yu et", "yu et al. 2010", "al. 2010 .
", "tgf beta receptor signaling is", "beta receptor signaling is downregulated", "receptor signaling is downregulated by", "signaling is downregulated by proteasome", "is downregulated by proteasome and", "downregulated by proteasome and lysosome", "by proteasome and lysosome mediated", "proteasome and lysosome mediated degradation", "and lysosome mediated degradation of", "lysosome mediated degradation of ubiquitinated", "mediated degradation of ubiquitinated tgfbr1", "of ubiquitinated tgfbr1 smad2", "ubiquitinated tgfbr1 smad2 and", "tgfbr1 smad2 and smad3", "smad2 and smad3 as", "and smad3 as well", "smad3 as well as", "as well as by dephosphorylation", "well as by dephosphorylation of", "as by dephosphorylation of tgfbr1", "dephosphorylation of tgfbr1 smad2", "of tgfbr1 smad2 and", "tgfbr1 smad2 and smad3.", "smad2 and smad3.

in the", "and smad3.

in the nucleus", "

in the nucleus smad2/3:smad4", "the nucleus smad2/3:smad4 complex", "nucleus smad2/3:smad4 complex stimulates", "smad2/3:smad4 complex stimulates transcription of", "complex stimulates transcription of smad7", "transcription of smad7 an", "of smad7 an inhibitory", "smad7 an inhibitory smad", "an inhibitory smad i", "inhibitory smad i smad", "smad i smad .", "i smad . smad7 binds", "smad . smad7 binds phosphorylated", ". smad7 binds phosphorylated tgfbr1", "smad7 binds phosphorylated tgfbr1 and", "binds phosphorylated tgfbr1 and competes", "phosphorylated tgfbr1 and competes with", "tgfbr1 and competes with the", "and competes with the binding", "competes with the binding of", "with the binding of smad2", "the binding of smad2 and", "binding of smad2 and smad3", "smad2 and smad3 hayashi", "and smad3 hayashi et", "smad3 hayashi et al.", "et al. 1997 nakao", "al. 1997 nakao et", "1997 nakao et al.", "nakao et al. 1997 .", "et al. 1997 . binding", "al. 1997 . binding of", "1997 . binding of smad7", ". binding of smad7 to", "binding of smad7 to tgbr1", "of smad7 to tgbr1 can", "smad7 to tgbr1 can be", "to tgbr1 can be stabilized", "tgbr1 can be stabilized by", "can be stabilized by strap", "stabilized by strap a", "by strap a protein", "strap a protein that", "a protein that simultaneously binds", "protein that simultaneously binds smad7", "that simultaneously binds smad7 and", "simultaneously binds smad7 and tgfbr1", "smad7 and tgfbr1 datta", "and tgfbr1 datta et", "tgfbr1 datta et al.", "datta et al. 2000 .", "et al. 2000 . bambi", "al. 2000 . bambi simultaneously", "2000 . bambi simultaneously binds", ". bambi simultaneously binds smad7", "bambi simultaneously binds smad7 and", "simultaneously binds smad7 and activated", "binds smad7 and activated tgfbr1", "and activated tgfbr1 leading", "activated tgfbr1 leading to", "tgfbr1 leading to downregulation", "leading to downregulation of tgf", "to downregulation of tgf beta", "of tgf beta receptor complex", "tgf beta receptor complex signaling", "receptor complex signaling onichtchouk", "complex signaling onichtchouk et", "signaling onichtchouk et al.", "et al. 1999 yan", "al. 1999 yan et", "1999 yan et al.", "yan et al. 2009 .
", "et al. 2009 .

in", "al. 2009 .

in addition", "2009 .

in addition to", ".

in addition to competing", "
in addition to competing with", "addition to competing with smad2/3", "to competing with smad2/3 binding", "competing with smad2/3 binding to", "with smad2/3 binding to tgfbr1", "binding to tgfbr1 smad7", "to tgfbr1 smad7 recruits", "tgfbr1 smad7 recruits protein", "smad7 recruits protein phosphatase pp1", "recruits protein phosphatase pp1 to", "protein phosphatase pp1 to phosphorylated", "phosphatase pp1 to phosphorylated tgfbr1", "to phosphorylated tgfbr1 by", "phosphorylated tgfbr1 by binding", "tgfbr1 by binding to", "by binding to the pp1", "binding to the pp1 regulatory", "to the pp1 regulatory subunit", "the pp1 regulatory subunit ppp1r15a", "regulatory subunit ppp1r15a gadd34", "subunit ppp1r15a gadd34 .", "ppp1r15a gadd34 . pp1", "gadd34 . pp1 dephosphorylates tgfbr1", "pp1 dephosphorylates tgfbr1 preventing", "dephosphorylates tgfbr1 preventing the", "tgfbr1 preventing the activation", "preventing the activation of smad2/3", "the activation of smad2/3 and", "activation of smad2/3 and propagation", "of smad2/3 and propagation of", "smad2/3 and propagation of tgf", "and propagation of tgf beta", "propagation of tgf beta signal", "tgf beta signal shi", "beta signal shi et", "signal shi et al.", "shi et al. 2004 .", "et al. 2004 .
", "al. 2004 .

smad7", "2004 .

smad7 associates", ".

smad7 associates with", "

smad7 associates with several", "
smad7 associates with several ubiquitin", "associates with several ubiquitin ligases", "several ubiquitin ligases smurf1", "ligases smurf1 ebisawa", "smurf1 ebisawa et al.", "et al. 2001 suzuki", "al. 2001 suzuki et", "2001 suzuki et al.", "et al. 2002 tajima", "al. 2002 tajima et", "2002 tajima et al.", "et al. 2003 chong", "al. 2003 chong et", "2003 chong et al.", "al. 2010 smurf2", "smurf2 kavsak et al.", "et al. 2000 ogunjimi", "al. 2000 ogunjimi et", "2000 ogunjimi et al.", "al. 2005 and", "2005 and nedd4l", "and nedd4l kuratomi et", "nedd4l kuratomi et al.", "2005 and recruits", "and recruits them to phosphorylated", "recruits them to phosphorylated tgfbr1", "them to phosphorylated tgfbr1 within", "to phosphorylated tgfbr1 within tgfbr", "phosphorylated tgfbr1 within tgfbr complex.", "tgfbr1 within tgfbr complex. smurf1", "tgfbr complex. smurf1 smurf2", "complex. smurf1 smurf2 and", "smurf1 smurf2 and nedd4l", "smurf2 and nedd4l ubiquitinate tgfbr1", "nedd4l ubiquitinate tgfbr1 and", "ubiquitinate tgfbr1 and smad7", "and smad7 targeting", "smad7 targeting tgfbr", "targeting tgfbr complex for proteasome", "tgfbr complex for proteasome and", "complex for proteasome and lysosome", "for proteasome and lysosome dependent", "proteasome and lysosome dependent degradation", "lysosome dependent degradation ebisawa", "dependent degradation ebisawa et", "degradation ebisawa et al.", "et al. 2001 kavsak", "al. 2001 kavsak et", "2001 kavsak et al.", "et al. 2000 kuratomi", "al. 2000 kuratomi et", "2000 kuratomi et al.", "kuratomi et al. 2005 .", "et al. 2005 . the", "al. 2005 . the ubiquitination", "2005 . the ubiquitination of", ". the ubiquitination of tgfbr1", "the ubiquitination of tgfbr1 can", "ubiquitination of tgfbr1 can be", "of tgfbr1 can be reversed", "tgfbr1 can be reversed by", "can be reversed by deubiquitinating", "be reversed by deubiquitinating enzymes", "by deubiquitinating enzymes uchl5", "enzymes uchl5 uch37", "uchl5 uch37 and", "and usp15 which may", "usp15 which may be", "which may be recruited to", "may be recruited to ubiquitinated", "be recruited to ubiquitinated tgfbr1", "recruited to ubiquitinated tgfbr1 by", "to ubiquitinated tgfbr1 by smad7", "tgfbr1 by smad7 wicks", "by smad7 wicks et", "smad7 wicks et al.", "et al. 2005 eichhorn", "al. 2005 eichhorn et", "2005 eichhorn et al.", "eichhorn et al. 2012 .", "et al. 2012 .
", "al. 2012 .

basal", "2012 .

basal levels", ".

basal levels of", "

basal levels of smad2", "
basal levels of smad2 and", "levels of smad2 and smad3", "of smad2 and smad3 are", "smad2 and smad3 are maintained", "and smad3 are maintained by", "smad3 are maintained by smurf2", "are maintained by smurf2 and", "maintained by smurf2 and stub1", "by smurf2 and stub1 ubiquitin", "smurf2 and stub1 ubiquitin ligases.", "and stub1 ubiquitin ligases. smurf2", "stub1 ubiquitin ligases. smurf2 is", "ubiquitin ligases. smurf2 is able", "ligases. smurf2 is able to", "smurf2 is able to bind", "is able to bind and", "able to bind and ubiquitinate", "to bind and ubiquitinate smad2", "and ubiquitinate smad2 leading", "ubiquitinate smad2 leading to", "smad2 leading to smad2", "to smad2 degradation zhang", "smad2 degradation zhang et", "degradation zhang et al.", "al. 2001 but", "2001 but this", "but this has been questioned", "this has been questioned by", "has been questioned by a", "been questioned by a recent", "questioned by a recent study", "by a recent study of", "a recent study of smurf2", "recent study of smurf2 knockout", "study of smurf2 knockout mice", "smurf2 knockout mice tang", "knockout mice tang et", "mice tang et al.", "tang et al. 2011 .", "et al. 2011 . stub1", "2011 . stub1 chip", "stub1 chip binds", "chip binds and ubiquitinates", "and ubiquitinates smad3 leading", "ubiquitinates smad3 leading to", "smad3 leading to smad3", "to smad3 degradation li", "smad3 degradation li et", "degradation li et al.", "et al. 2004 xin", "al. 2004 xin et", "2004 xin et al.", "xin et al. 2005 .", "et al. 2005 . pmepa1", "al. 2005 . pmepa1 can", "2005 . pmepa1 can bind", ". pmepa1 can bind and", "pmepa1 can bind and sequester", "can bind and sequester unphosphorylated", "bind and sequester unphosphorylated smad2", "and sequester unphosphorylated smad2 and", "sequester unphosphorylated smad2 and smad3", "smad2 and smad3 preventing", "and smad3 preventing their", "smad3 preventing their activation", "preventing their activation in response", "their activation in response to", "activation in response to tgf", "in response to tgf beta", "response to tgf beta signaling.", "to tgf beta signaling. in", "tgf beta signaling. in addition", "signaling. in addition pmepa1", "in addition pmepa1 can", "addition pmepa1 can bind", "can bind and sequester phosphorylated", "bind and sequester phosphorylated smad2", "and sequester phosphorylated smad2 and", "sequester phosphorylated smad2 and smad3", "and smad3 preventing formation", "smad3 preventing formation of", "preventing formation of smad2/3:smad4 heterotrimer", "formation of smad2/3:smad4 heterotrimer complexes", "smad2/3:smad4 heterotrimer complexes watanabe", "heterotrimer complexes watanabe et", "complexes watanabe et al.", "watanabe et al. 2010 .", "et al. 2010 . a", "al. 2010 . a protein", "2010 . a protein phosphatase", ". a protein phosphatase mtmr4", "protein phosphatase mtmr4 residing", "phosphatase mtmr4 residing in", "mtmr4 residing in the", "residing in the membrane of", "in the membrane of early", "the membrane of early endosomes", "of early endosomes can", "early endosomes can dephosphorylate", "endosomes can dephosphorylate activated", "can dephosphorylate activated smad2 and", "dephosphorylate activated smad2 and smad3", "preventing formation of smad2/3:smad4 complexes", "of smad2/3:smad4 complexes yu", "smad2/3:smad4 complexes yu et", "complexes yu et al.", "yu et al. 2010 .", "et al. 2010 .
" ] }, { "record_id": "GLY_000594_1_226", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2173796", "r hsa", "hsa 2173796", "r hsa 2173796" ] }, { "record_id": "GLY_000594_1_226", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "smad2/smad3:smad4 heterotrimer", "heterotrimer regulates", "regulates transcription", "smad2/smad3:smad4 heterotrimer regulates", "heterotrimer regulates transcription", "smad2/smad3:smad4 heterotrimer regulates transcription", "after phosphorylated", "phosphorylated smad2", "smad2 and/or", "and/or smad3", "smad3 form", "form a", "a heterotrimer", "heterotrimer with", "with smad4", "smad2/3:smad4 complex", "complex translocates", "translocates to", "to the", "the nucleus", "xu et", "et al.", "al. 2000", "kurisaki et", "al. 2001", "xiao et", "al. 2003", "2003 .", ". in", "in the", "linker regions", "regions of", "of smad2", "smad2 and", "and smad3", "smad3 within", "within smad2/3:smad4", "complex can", "can be", "be phosphorylated", "phosphorylated by", "by cdk8", "cdk8 associated", "associated with", "with cyclin", "cyclin c", "or cdk9", "cdk9 associated", "cyclin t", "cdk9:ccnt .", ". cdk8/cdk9", "cdk8/cdk9 mediated", "mediated phosphorylation", "phosphorylation of", "of smad2/3", "smad2/3 enhances", "enhances transcriptional", "transcriptional activity", "activity of", "of smad2/3:smad4", "but also", "also primes", "primes it", "it for", "for ubiquitination", "ubiquitination and", "and consequent", "consequent degradation", "alarcon et", "al. 2009", "2009 .", ".

the", "

the transfer", "transfer of", "complex to", "nucleus can", "be assisted", "assisted by", "by other", "other proteins", "such as", "as wwtr1.", "wwtr1. in", "in human", "human embryonic", "embryonic cells", "binds smad2/3:smad4", "smad2/3:smad4 heterotrimer", "heterotrimer and", "and mediates", "mediates tgf", "tgf beta", "beta dependent", "dependent nuclear", "nuclear accumulation", "accumulation of", "of smad2/3:smad4.", "smad2/3:smad4. the", "the complex", "complex of", "of wwtr1", "wwtr1 and", "and smad2/3:smad4", "smad2/3:smad4 binds", "binds promoters", "promoters of", "of smad7", "smad7 and", "and serpine1", "pai 1", "1 i.e.", "i.e. plasminogen", "plasminogen activator", "activator inhibitor", "inhibitor 1", "genes and", "and stimulates", "stimulates their", "their transcription", "varelas et", "al. 2008", "2008 .", ". stimulation", "stimulation of", "smad7 transcription", "transcription by", "by smad2/3:smad4", "smad2/3:smad4 represents", "represents a", "a negative", "negative feedback", "feedback loop", "loop in", "in tgf", "beta receptor", "receptor signaling.", "signaling. smad7", "smad7 can", "be downregulated", "downregulated by", "by rnf111", "rnf111 ubiquitin", "ubiquitin ligase", "which binds", "binds and", "and ubiquitinates", "ubiquitinates smad7", "targeting it", "for degradation", "koinuma et", ".

smad2/3:smad4", "

smad2/3:smad4 heterotrimer", "heterotrimer also", "also binds", "binds the", "of rbl1", "e2f4/5 and", "and tfdp1/2", "dp1/2 .", ". the", "the resulting", "resulting complex", "complex binds", "binds myc", "myc promoter", "promoter and", "and inhibits", "inhibits myc", "myc transcription.", "transcription. inhibition", "inhibition of", "of myc", "myc transcription", "transcription contributes", "contributes to", "to anti", "anti proliferative", "proliferative effect", "effect of", "of tgf", "chen et", "al. 2002", "2002 .", ". smad2/3:smad4", "also associates", "associates with", "with transcription", "transcription factor", "factor sp1.", "sp1. smad2/3:smad4:sp1", "smad2/3:smad4:sp1 complex", "complex stimulates", "stimulates transcription", "transcription of", "of a", "a cdk", "cdk inhibitor", "inhibitor cdkn2b", "p15 ink4b", "also contributing", "contributing to", "the anti", "feng et", "2000 .", ".

men1", "a transcription", "factor tumor", "tumor suppressor", "suppressor mutated", "mutated in", "in a", "a familial", "familial cancer", "cancer syndrome", "syndrome multiple", "multiple endocrine", "endocrine neoplasia", "neoplasia type", "type 1", "forms a", "a complex", "complex with", "with smad2/3:smad4", "but transcriptional", "transcriptional targets", "targets of", "of smad2/3:smad4:men1", "smad2/3:smad4:men1 have", "have not", "not been", "been elucidated", "kaji et", "sowa et", "al. 2004", "canaff et", "al. 2012", "2012 .", ".

junb", "

junb is", "is also", "also an", "an established", "established transcriptional", "transcriptional target", "target of", "wong et", "al. 1999", "1999 .", "after phosphorylated smad2", "phosphorylated smad2 and/or", "smad2 and/or smad3", "and/or smad3 form", "smad3 form a", "form a heterotrimer", "a heterotrimer with", "heterotrimer with smad4", "smad4 smad2/3:smad4", "smad2/3:smad4 complex translocates", "complex translocates to", "translocates to the", "to the nucleus", "nucleus xu", "xu et al.", "et al. 2000", "2000 kurisaki", "kurisaki et al.", "et al. 2001", "2001 xiao", "xiao et al.", "et al. 2003", "al. 2003 .", "2003 . in", ". in the", "in the nucleus", "nucleus linker", "linker regions of", "regions of smad2", "of smad2 and", "smad2 and smad3", "and smad3 within", "smad3 within smad2/3:smad4", "within smad2/3:smad4 complex", "smad2/3:smad4 complex can", "complex can be", "can be phosphorylated", "be phosphorylated by", "phosphorylated by cdk8", "by cdk8 associated", "cdk8 associated with", "associated with cyclin", "with cyclin c", "c cdk8:ccnc", "cdk8:ccnc or", "or cdk9 associated", "cdk9 associated with", "with cyclin t", "t cdk9:ccnt", "cdk9:ccnt . cdk8/cdk9", ". cdk8/cdk9 mediated", "cdk8/cdk9 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of smad2/3", "of smad2/3 enhances", "smad2/3 enhances transcriptional", "enhances transcriptional activity", "transcriptional activity of", "activity of smad2/3:smad4", "of smad2/3:smad4 complex", "complex but", "but also primes", "also primes it", "primes it for", "it for ubiquitination", "for ubiquitination and", "ubiquitination and consequent", "and consequent degradation", "degradation alarcon", "alarcon et al.", "et al. 2009", "al. 2009 .", "2009 .

the", ".

the transfer", "

the transfer of", "transfer of smad2/3:smad4", "smad2/3:smad4 complex to", "complex to the", "the nucleus can", "nucleus can be", "can be assisted", "be assisted by", "assisted by other", "by other proteins", "proteins such", "such as wwtr1.", "as wwtr1. in", "wwtr1. in human", "in human embryonic", "human embryonic cells", "cells wwtr1", "wwtr1 taz", "taz binds", "binds smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer and", "heterotrimer and mediates", "and mediates tgf", "mediates tgf beta", "tgf beta dependent", "beta dependent nuclear", "dependent nuclear accumulation", "nuclear accumulation of", "accumulation of smad2/3:smad4.", "of smad2/3:smad4. the", "smad2/3:smad4. the complex", "the complex of", "complex of wwtr1", "of wwtr1 and", "wwtr1 and smad2/3:smad4", "and smad2/3:smad4 binds", "smad2/3:smad4 binds promoters", "binds promoters of", "promoters of smad7", "of smad7 and", "smad7 and serpine1", "serpine1 pai", "pai 1 i.e.", "1 i.e. plasminogen", "i.e. plasminogen activator", "plasminogen activator inhibitor", "activator inhibitor 1", "1 genes", "genes and stimulates", "and stimulates their", "stimulates their transcription", "transcription varelas", "varelas et al.", "et al. 2008", "al. 2008 .", "2008 . stimulation", ". stimulation of", "stimulation of smad7", "of smad7 transcription", "smad7 transcription by", "transcription by smad2/3:smad4", "by smad2/3:smad4 represents", "smad2/3:smad4 represents a", "represents a negative", "a negative feedback", "negative feedback loop", "feedback loop in", "loop in tgf", "in tgf beta", "tgf beta receptor", "beta receptor signaling.", "receptor signaling. smad7", "signaling. smad7 can", "smad7 can be", "can be downregulated", "be downregulated by", "downregulated by rnf111", "by rnf111 ubiquitin", "rnf111 ubiquitin ligase", "ligase arkadia", "which binds and", "binds and ubiquitinates", "and ubiquitinates smad7", "smad7 targeting", "targeting it for", "it for degradation", "degradation koinuma", "koinuma et al.", "2003 .

smad2/3:smad4", ".

smad2/3:smad4 heterotrimer", "

smad2/3:smad4 heterotrimer also", "heterotrimer also binds", "also binds the", "binds the complex", "complex of rbl1", "rbl1 p107", "e2f4/5 and tfdp1/2", "tfdp1/2 dp1/2", "dp1/2 . the", ". the resulting", "the resulting complex", "resulting complex binds", "complex binds myc", "binds myc promoter", "myc promoter and", "promoter and inhibits", "and inhibits myc", "inhibits myc transcription.", "myc transcription. inhibition", "transcription. inhibition of", "inhibition of myc", "of myc transcription", "myc transcription contributes", "transcription contributes to", "contributes to anti", "to anti proliferative", "anti proliferative effect", "proliferative effect of", "effect of tgf", "of tgf beta", "beta chen", "chen et al.", "et al. 2002", "al. 2002 .", "2002 . smad2/3:smad4", ". smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer also", "heterotrimer also associates", "also associates with", "associates with transcription", "with transcription factor", "transcription factor sp1.", "factor sp1. smad2/3:smad4:sp1", "sp1. smad2/3:smad4:sp1 complex", "smad2/3:smad4:sp1 complex stimulates", "complex stimulates transcription", "stimulates transcription of", "transcription of a", "of a cdk", "a cdk inhibitor", "cdk inhibitor cdkn2b", "cdkn2b p15", "also contributing to", "contributing to the", "to the anti", "the anti proliferative", "beta feng", "feng et al.", "al. 2000 .", "2000 .

men1", "

men1 menin", "a transcription factor", "transcription factor tumor", "factor tumor suppressor", "tumor suppressor mutated", "suppressor mutated in", "mutated in a", "in a familial", "a familial cancer", "familial cancer syndrome", "cancer syndrome multiple", "syndrome multiple endocrine", "multiple endocrine neoplasia", "endocrine neoplasia type", "neoplasia type 1", "1 forms", "forms a complex", "a complex with", "complex with smad2/3:smad4", "with smad2/3:smad4 heterotrimer", "heterotrimer but", "but transcriptional targets", "transcriptional targets of", "targets of smad2/3:smad4:men1", "of smad2/3:smad4:men1 have", "smad2/3:smad4:men1 have not", "have not been", "not been elucidated", "elucidated kaji", "kaji et al.", "2001 sowa", "sowa et al.", "et al. 2004", "2004 canaff", "canaff et al.", "et al. 2012", "al. 2012 .", "2012 .

junb", ".

junb is", "

junb is also", "is also an", "also an established", "an established transcriptional", "established transcriptional target", "transcriptional target of", "target of smad2/3:smad4", "complex wong", "wong et al.", "et al. 1999", "al. 1999 .", "after phosphorylated smad2 and/or", "phosphorylated smad2 and/or smad3", "smad2 and/or smad3 form", "and/or smad3 form a", "smad3 form a heterotrimer", "form a heterotrimer with", "a heterotrimer with smad4", "with smad4 smad2/3:smad4", "smad4 smad2/3:smad4 complex", "smad2/3:smad4 complex translocates to", "complex translocates to the", "translocates to the nucleus", "the nucleus xu", "nucleus xu et", "xu et al. 2000", "al. 2000 kurisaki", "2000 kurisaki et", "kurisaki et al. 2001", "al. 2001 xiao", "2001 xiao et", "xiao et al. 2003", "et al. 2003 .", "al. 2003 . in", "2003 . in the", ". in the nucleus", "the nucleus linker", "nucleus linker regions", "linker regions of smad2", "regions of smad2 and", "of smad2 and smad3", "smad2 and smad3 within", "and smad3 within smad2/3:smad4", "smad3 within smad2/3:smad4 complex", "within smad2/3:smad4 complex can", "smad2/3:smad4 complex can be", "complex can be phosphorylated", "can be phosphorylated by", "be phosphorylated by cdk8", "phosphorylated by cdk8 associated", "by cdk8 associated with", "cdk8 associated with cyclin", "associated with cyclin c", "cyclin c cdk8:ccnc", "cdk8:ccnc or cdk9", "or cdk9 associated with", "cdk9 associated with cyclin", "associated with cyclin t", "cyclin t cdk9:ccnt", "t cdk9:ccnt .", "cdk9:ccnt . cdk8/cdk9 mediated", ". cdk8/cdk9 mediated phosphorylation", "cdk8/cdk9 mediated phosphorylation of", "mediated phosphorylation of smad2/3", "phosphorylation of smad2/3 enhances", "of smad2/3 enhances transcriptional", "smad2/3 enhances transcriptional activity", "enhances transcriptional activity of", "transcriptional activity of smad2/3:smad4", "activity of smad2/3:smad4 complex", "smad2/3:smad4 complex but", "complex but also", "but also primes it", "also primes it for", "primes it for ubiquitination", "it for ubiquitination and", "for ubiquitination and consequent", "ubiquitination and consequent degradation", "consequent degradation alarcon", "degradation alarcon et", "alarcon et al. 2009", "et al. 2009 .", "al. 2009 .

the", "2009 .

the transfer", ".

the transfer of", "

the transfer of smad2/3:smad4", "transfer of smad2/3:smad4 complex", "of smad2/3:smad4 complex to", "smad2/3:smad4 complex to the", "complex to the nucleus", "to the nucleus can", "the nucleus can be", "nucleus can be assisted", "can be assisted by", "be assisted by other", "assisted by other proteins", "other proteins such", "proteins such as", "such as wwtr1. in", "as wwtr1. in human", "wwtr1. in human embryonic", "in human embryonic cells", "embryonic cells wwtr1", "taz binds smad2/3:smad4", "binds smad2/3:smad4 heterotrimer and", "smad2/3:smad4 heterotrimer and mediates", "heterotrimer and mediates tgf", "and mediates tgf beta", "mediates tgf beta dependent", "tgf beta dependent nuclear", "beta dependent nuclear accumulation", "dependent nuclear accumulation of", "nuclear accumulation of smad2/3:smad4.", "accumulation of smad2/3:smad4. the", "of smad2/3:smad4. the complex", "smad2/3:smad4. the complex of", "the complex of wwtr1", "complex of wwtr1 and", "of wwtr1 and smad2/3:smad4", "wwtr1 and smad2/3:smad4 binds", "and smad2/3:smad4 binds promoters", "smad2/3:smad4 binds promoters of", "binds promoters of smad7", "promoters of smad7 and", "of smad7 and serpine1", "and serpine1 pai", "serpine1 pai 1", "pai 1 i.e. plasminogen", "1 i.e. plasminogen activator", "i.e. plasminogen activator inhibitor", "plasminogen activator inhibitor 1", "inhibitor 1 genes", "1 genes and", "genes and stimulates their", "and stimulates their transcription", "their transcription varelas", "transcription varelas et", "varelas et al. 2008", "et al. 2008 .", "al. 2008 . stimulation", "2008 . stimulation of", ". stimulation of smad7", "stimulation of smad7 transcription", "of smad7 transcription by", "smad7 transcription by smad2/3:smad4", "transcription by smad2/3:smad4 represents", "by smad2/3:smad4 represents a", "smad2/3:smad4 represents a negative", "represents a negative feedback", "a negative feedback loop", "negative feedback loop in", "feedback loop in tgf", "loop in tgf beta", "in tgf beta receptor", "tgf beta receptor signaling.", "beta receptor signaling. smad7", "receptor signaling. smad7 can", "signaling. smad7 can be", "smad7 can be downregulated", "can be downregulated by", "be downregulated by rnf111", "downregulated by rnf111 ubiquitin", "by rnf111 ubiquitin ligase", "ubiquitin ligase arkadia", "arkadia which", "which binds and ubiquitinates", "binds and ubiquitinates smad7", "ubiquitinates smad7 targeting", "smad7 targeting it", "targeting it for degradation", "for degradation koinuma", "degradation koinuma et", "koinuma et al. 2003", "al. 2003 .

smad2/3:smad4", "2003 .

smad2/3:smad4 heterotrimer", ".

smad2/3:smad4 heterotrimer also", "

smad2/3:smad4 heterotrimer also binds", "heterotrimer also binds the", "also binds the complex", "binds the complex of", "the complex of rbl1", "of rbl1 p107", "p107 e2f4/5", "and tfdp1/2 dp1/2", "tfdp1/2 dp1/2 .", "dp1/2 . the resulting", ". the resulting complex", "the resulting complex binds", "resulting complex binds myc", "complex binds myc promoter", "binds myc promoter and", "myc promoter and inhibits", "promoter and inhibits myc", "and inhibits myc transcription.", "inhibits myc transcription. inhibition", "myc transcription. inhibition of", "transcription. inhibition of myc", "inhibition of myc transcription", "of myc transcription contributes", "myc transcription contributes to", "transcription contributes to anti", "contributes to anti proliferative", "to anti proliferative effect", "anti proliferative effect of", "proliferative effect of tgf", "effect of tgf beta", "tgf beta chen", "beta chen et", "chen et al. 2002", "et al. 2002 .", "al. 2002 . smad2/3:smad4", "2002 . smad2/3:smad4 heterotrimer", ". smad2/3:smad4 heterotrimer also", "smad2/3:smad4 heterotrimer also associates", "heterotrimer also associates with", "also associates with transcription", "associates with transcription factor", "with transcription factor sp1.", "transcription factor sp1. smad2/3:smad4:sp1", "factor sp1. smad2/3:smad4:sp1 complex", "sp1. smad2/3:smad4:sp1 complex stimulates", "smad2/3:smad4:sp1 complex stimulates transcription", "complex stimulates transcription of", "stimulates transcription of a", "transcription of a cdk", "of a cdk inhibitor", "a cdk inhibitor cdkn2b", "inhibitor cdkn2b p15", "cdkn2b p15 ink4b", "ink4b also", "also contributing to the", "contributing to the anti", "to the anti proliferative", "the anti proliferative effect", "tgf beta feng", "beta feng et", "feng et al. 2000", "et al. 2000 .", "al. 2000 .

men1", ".

men1 menin", "menin a", "a transcription factor tumor", "transcription factor tumor suppressor", "factor tumor suppressor mutated", "tumor suppressor mutated in", "suppressor mutated in a", "mutated in a familial", "in a familial cancer", "a familial cancer syndrome", "familial cancer syndrome multiple", "cancer syndrome multiple endocrine", "syndrome multiple endocrine neoplasia", "multiple endocrine neoplasia type", "endocrine neoplasia type 1", "type 1 forms", "1 forms a", "forms a complex with", "a complex with smad2/3:smad4", "complex with smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer but", "heterotrimer but transcriptional", "but transcriptional targets of", "transcriptional targets of smad2/3:smad4:men1", "targets of smad2/3:smad4:men1 have", "of smad2/3:smad4:men1 have not", "smad2/3:smad4:men1 have not been", "have not been elucidated", "been elucidated kaji", "elucidated kaji et", "kaji et al. 2001", "al. 2001 sowa", "2001 sowa et", "sowa et al. 2004", "al. 2004 canaff", "2004 canaff et", "canaff et al. 2012", "et al. 2012 .", "al. 2012 .

junb", "2012 .

junb is", ".

junb is also", "

junb is also an", "is also an established", "also an established transcriptional", "an established transcriptional target", "established transcriptional target of", "transcriptional target of smad2/3:smad4", "target of smad2/3:smad4 complex", "smad2/3:smad4 complex wong", "complex wong et", "wong et al. 1999", "et al. 1999 .", "after phosphorylated smad2 and/or smad3", "phosphorylated smad2 and/or smad3 form", "smad2 and/or smad3 form a", "and/or smad3 form a heterotrimer", "smad3 form a heterotrimer with", "form a heterotrimer with smad4", "heterotrimer with smad4 smad2/3:smad4", "with smad4 smad2/3:smad4 complex", "smad4 smad2/3:smad4 complex translocates", "smad2/3:smad4 complex translocates to the", "complex translocates to the nucleus", "to the nucleus xu", "the nucleus xu et", "nucleus xu et al.", "et al. 2000 kurisaki", "al. 2000 kurisaki et", "2000 kurisaki et al.", "et al. 2001 xiao", "al. 2001 xiao et", "2001 xiao et al.", "xiao et al. 2003 .", "et al. 2003 . in", "al. 2003 . in the", "2003 . in the nucleus", "in the nucleus linker", "the nucleus linker regions", "nucleus linker regions of", "linker regions of smad2 and", "regions of smad2 and smad3", "of smad2 and smad3 within", "smad2 and smad3 within smad2/3:smad4", "and smad3 within smad2/3:smad4 complex", "smad3 within smad2/3:smad4 complex can", "within smad2/3:smad4 complex can be", "smad2/3:smad4 complex can be phosphorylated", "complex can be phosphorylated by", "can be phosphorylated by cdk8", "be phosphorylated by cdk8 associated", "phosphorylated by cdk8 associated with", "by cdk8 associated with cyclin", "cdk8 associated with cyclin c", "with cyclin c cdk8:ccnc", "c cdk8:ccnc or", "cdk8:ccnc or cdk9 associated", "or cdk9 associated with cyclin", "cdk9 associated with cyclin t", "with cyclin t cdk9:ccnt", "cyclin t cdk9:ccnt .", "t cdk9:ccnt . cdk8/cdk9", "cdk9:ccnt . cdk8/cdk9 mediated phosphorylation", ". cdk8/cdk9 mediated phosphorylation of", "cdk8/cdk9 mediated phosphorylation of smad2/3", "mediated phosphorylation of smad2/3 enhances", "phosphorylation of smad2/3 enhances transcriptional", "of smad2/3 enhances transcriptional activity", "smad2/3 enhances transcriptional activity of", "enhances transcriptional activity of smad2/3:smad4", "transcriptional activity of smad2/3:smad4 complex", "of smad2/3:smad4 complex but", "smad2/3:smad4 complex but also", "complex but also primes", "but also primes it for", "also primes it for ubiquitination", "primes it for ubiquitination and", "it for ubiquitination and consequent", "for ubiquitination and consequent degradation", "and consequent degradation alarcon", "consequent degradation alarcon et", "degradation alarcon et al.", "alarcon et al. 2009 .", "et al. 2009 .

the", "al. 2009 .

the transfer", "2009 .

the transfer of", ".

the transfer of smad2/3:smad4", "

the transfer of smad2/3:smad4 complex", "transfer of smad2/3:smad4 complex to", "of smad2/3:smad4 complex to the", "smad2/3:smad4 complex to the nucleus", "complex to the nucleus can", "to the nucleus can be", "the nucleus can be assisted", "nucleus can be assisted by", "can be assisted by other", "be assisted by other proteins", "by other proteins such", "other proteins such as", "proteins such as wwtr1.", "such as wwtr1. in human", "as wwtr1. in human embryonic", "wwtr1. in human embryonic cells", "human embryonic cells wwtr1", "cells wwtr1 taz", "wwtr1 taz binds", "taz binds smad2/3:smad4 heterotrimer", "binds smad2/3:smad4 heterotrimer and mediates", "smad2/3:smad4 heterotrimer and mediates tgf", "heterotrimer and mediates tgf beta", "and mediates tgf beta dependent", "mediates tgf beta dependent nuclear", "tgf beta dependent nuclear accumulation", "beta dependent nuclear accumulation of", "dependent nuclear accumulation of smad2/3:smad4.", "nuclear accumulation of smad2/3:smad4. the", "accumulation of smad2/3:smad4. the complex", "of smad2/3:smad4. the complex of", "smad2/3:smad4. the complex of wwtr1", "the complex of wwtr1 and", "complex of wwtr1 and smad2/3:smad4", "of wwtr1 and smad2/3:smad4 binds", "wwtr1 and smad2/3:smad4 binds promoters", "and smad2/3:smad4 binds promoters of", "smad2/3:smad4 binds promoters of smad7", "binds promoters of smad7 and", "promoters of smad7 and serpine1", "smad7 and serpine1 pai", "and serpine1 pai 1", "serpine1 pai 1 i.e.", "pai 1 i.e. plasminogen activator", "1 i.e. plasminogen activator inhibitor", "i.e. plasminogen activator inhibitor 1", "activator inhibitor 1 genes", "inhibitor 1 genes and", "1 genes and stimulates", "genes and stimulates their transcription", "stimulates their transcription varelas", "their transcription varelas et", "transcription varelas et al.", "varelas et al. 2008 .", "et al. 2008 . stimulation", "al. 2008 . stimulation of", "2008 . stimulation of smad7", ". stimulation of smad7 transcription", "stimulation of smad7 transcription by", "of smad7 transcription by smad2/3:smad4", "smad7 transcription by smad2/3:smad4 represents", "transcription by smad2/3:smad4 represents a", "by smad2/3:smad4 represents a negative", "smad2/3:smad4 represents a negative feedback", "represents a negative feedback loop", "a negative feedback loop in", "negative feedback loop in tgf", "feedback loop in tgf beta", "loop in tgf beta receptor", "in tgf beta receptor signaling.", "tgf beta receptor signaling. smad7", "beta receptor signaling. smad7 can", "receptor signaling. smad7 can be", "signaling. smad7 can be downregulated", "smad7 can be downregulated by", "can be downregulated by rnf111", "be downregulated by rnf111 ubiquitin", "downregulated by rnf111 ubiquitin ligase", "rnf111 ubiquitin ligase arkadia", "arkadia which binds", "which binds and ubiquitinates smad7", "and ubiquitinates smad7 targeting", "ubiquitinates smad7 targeting it", "smad7 targeting it for", "it for degradation koinuma", "for degradation koinuma et", "degradation koinuma et al.", "koinuma et al. 2003 .", "et al. 2003 .

smad2/3:smad4", "al. 2003 .

smad2/3:smad4 heterotrimer", "2003 .

smad2/3:smad4 heterotrimer also", ".

smad2/3:smad4 heterotrimer also binds", "

smad2/3:smad4 heterotrimer also binds the", "heterotrimer also binds the complex", "also binds the complex of", "binds the complex of rbl1", "complex of rbl1 p107", "p107 e2f4/5 and", "e2f4/5 and tfdp1/2 dp1/2", "and tfdp1/2 dp1/2 .", "tfdp1/2 dp1/2 . the", "dp1/2 . the resulting complex", ". the resulting complex binds", "the resulting complex binds myc", "resulting complex binds myc promoter", "complex binds myc promoter and", "binds myc promoter and inhibits", "myc promoter and inhibits myc", "promoter and inhibits myc transcription.", "and inhibits myc transcription. inhibition", "inhibits myc transcription. inhibition of", "myc transcription. inhibition of myc", "transcription. inhibition of myc transcription", "inhibition of myc transcription contributes", "of myc transcription contributes to", "myc transcription contributes to anti", "transcription contributes to anti proliferative", "contributes to anti proliferative effect", "to anti proliferative effect of", "anti proliferative effect of tgf", "proliferative effect of tgf beta", "of tgf beta chen", "tgf beta chen et", "beta chen et al.", "chen et al. 2002 .", "et al. 2002 . smad2/3:smad4", "al. 2002 . smad2/3:smad4 heterotrimer", "2002 . smad2/3:smad4 heterotrimer also", ". smad2/3:smad4 heterotrimer also associates", "smad2/3:smad4 heterotrimer also associates with", "heterotrimer also associates with transcription", "also associates with transcription factor", "associates with transcription factor sp1.", "with transcription factor sp1. smad2/3:smad4:sp1", "transcription factor sp1. smad2/3:smad4:sp1 complex", "factor sp1. smad2/3:smad4:sp1 complex stimulates", "sp1. smad2/3:smad4:sp1 complex stimulates transcription", "smad2/3:smad4:sp1 complex stimulates transcription of", "complex stimulates transcription of a", "stimulates transcription of a cdk", "transcription of a cdk inhibitor", "of a cdk inhibitor cdkn2b", "cdk inhibitor cdkn2b p15", "inhibitor cdkn2b p15 ink4b", "p15 ink4b also", "ink4b also contributing", "also contributing to the anti", "contributing to the anti proliferative", "to the anti proliferative effect", "the anti proliferative effect of", "of tgf beta feng", "tgf beta feng et", "beta feng et al.", "feng et al. 2000 .", "et al. 2000 .

men1", "2000 .

men1 menin", "menin a transcription", "a transcription factor tumor suppressor", "transcription factor tumor suppressor mutated", "factor tumor suppressor mutated in", "tumor suppressor mutated in a", "suppressor mutated in a familial", "mutated in a familial cancer", "in a familial cancer syndrome", "a familial cancer syndrome multiple", "familial cancer syndrome multiple endocrine", "cancer syndrome multiple endocrine neoplasia", "syndrome multiple endocrine neoplasia type", "multiple endocrine neoplasia type 1", "neoplasia type 1 forms", "type 1 forms a", "1 forms a complex", "forms a complex with smad2/3:smad4", "a complex with smad2/3:smad4 heterotrimer", "with smad2/3:smad4 heterotrimer but", "smad2/3:smad4 heterotrimer but transcriptional", "heterotrimer but transcriptional targets", "but transcriptional targets of smad2/3:smad4:men1", "transcriptional targets of smad2/3:smad4:men1 have", "targets of smad2/3:smad4:men1 have not", "of smad2/3:smad4:men1 have not been", "smad2/3:smad4:men1 have not been elucidated", "not been elucidated kaji", "been elucidated kaji et", "elucidated kaji et al.", "et al. 2001 sowa", "al. 2001 sowa et", "2001 sowa et al.", "et al. 2004 canaff", "al. 2004 canaff et", "2004 canaff et al.", "canaff et al. 2012 .", "et al. 2012 .

junb", "al. 2012 .

junb is", "2012 .

junb is also", ".

junb is also an", "

junb is also an established", "is also an established transcriptional", "also an established transcriptional target", "an established transcriptional target of", "established transcriptional target of smad2/3:smad4", "transcriptional target of smad2/3:smad4 complex", "of smad2/3:smad4 complex wong", "smad2/3:smad4 complex wong et", "complex wong et al.", "wong et al. 1999 ." ] }, { "record_id": "GLY_000594_1_227", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2219530", "r hsa", "hsa 2219530", "r hsa 2219530" ] }, { "record_id": "GLY_000594_1_227", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "constitutive signaling", "signaling by", "by aberrant", "aberrant pi3k", "pi3k in", "in cancer", "constitutive signaling by", "signaling by aberrant", "by aberrant pi3k", "aberrant pi3k in", "pi3k in cancer", "constitutive signaling by aberrant", "signaling by aberrant pi3k", "by aberrant pi3k in", "aberrant pi3k in cancer", "constitutive signaling by aberrant pi3k", "signaling by aberrant pi3k in", "by aberrant pi3k in cancer", "by pi3k/akt", "pi3k/akt is", "is frequently", "frequently constitutively", "constitutively activated", "activated in", "cancer via", "via gain", "gain of", "of function", "function mutations", "mutations in", "in one", "one of", "of the", "the two", "two pi3k", "pi3k subunits", "encoding the", "the catalytic", "catalytic subunit", "subunit p110alpha", "or pik3r1", "the regulatory", "regulatory subunit", "subunit p85alpha", "p85alpha .", ". gain", "mutations activate", "activate pi3k", "pi3k signaling", "by diverse", "diverse mechanisms.", "mechanisms. mutations", "mutations affecting", "affecting the", "the helical", "helical domain", "domain of", "of pik3ca", "pik3ca and", "and mutations", "affecting nsh2", "nsh2 and", "and ish2", "ish2 domains", "domains of", "of pik3r1", "pik3r1 impair", "impair inhibitory", "inhibitory interactions", "interactions between", "between these", "these two", "two subunits", "subunits while", "while preserving", "preserving their", "their association.", "association. mutations", "in the", "catalytic domain", "pik3ca enable", "enable the", "the kinase", "kinase to", "to achieve", "achieve an", "an active", "active conformation.", "conformation. pi3k", "pi3k complexes", "complexes with", "with gain", "mutations therefore", "therefore produce", "produce pip3", "pip3 and", "and activate", "activate downstream", "downstream akt", "akt in", "the absence", "absence of", "of growth", "growth factors", "huang et", "et al.", "al. 2007", "zhao et", "al. 2005", "miled et", "horn et", "al. 2008", "sun et", "al. 2010", "jaiswal et", "al. 2009", "zhao and", "and vogt", "vogt 2010", "urick et", "al. 2011", "2011 .", "signaling by pi3k/akt", "by pi3k/akt is", "pi3k/akt is frequently", "is frequently constitutively", "frequently constitutively activated", "constitutively activated in", "activated in cancer", "in cancer 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"domains of pik3r1", "of pik3r1 impair", "pik3r1 impair inhibitory", "impair inhibitory interactions", "inhibitory interactions between", "interactions between these", "between these two", "these two subunits", "two subunits while", "subunits while preserving", "while preserving their", "preserving their association.", "their association. mutations", "association. mutations in", "mutations in the", "in the catalytic", "the catalytic domain", "catalytic domain of", "of pik3ca enable", "pik3ca enable the", "enable the kinase", "the kinase to", "kinase to achieve", "to achieve an", "achieve an active", "an active conformation.", "active conformation. pi3k", "conformation. pi3k complexes", "pi3k complexes with", "complexes with gain", "with gain of", "function mutations therefore", "mutations therefore produce", "therefore produce pip3", "produce pip3 and", "pip3 and activate", "and activate downstream", "activate downstream akt", "downstream akt in", "akt in the", "in the absence", "the absence of", "absence of growth", "of growth factors", "factors huang", "huang et al.", "et al. 2007", "2007 zhao", "zhao et al.", "et al. 2005", "2005 miled", "miled et al.", "2007 horn", "horn et al.", "et al. 2008", "2008 sun", "sun et al.", "et al. 2010", "2010 jaiswal", "jaiswal et al.", "et al. 2009", "2009 zhao", "zhao and vogt", "and vogt 2010", "2010 urick", "urick et al.", "et al. 2011", "al. 2011 .", "signaling by pi3k/akt is", "by pi3k/akt is frequently", "pi3k/akt is frequently constitutively", "is frequently constitutively activated", "frequently constitutively activated in", "constitutively activated in cancer", "activated in cancer via", "in cancer via gain", "cancer via gain of", "via gain of function", "gain of function mutations", "of function mutations in", "function mutations in one", "mutations in one of", "in one of the", "one of the two", "of the two pi3k", "the two pi3k subunits", "subunits pi3kca", "pi3kca encoding the", "encoding the catalytic subunit", "the catalytic subunit p110alpha", "subunit p110alpha or", "p110alpha or pik3r1", "or pik3r1 encoding", "pik3r1 encoding the", "encoding the regulatory subunit", "the regulatory subunit p85alpha", "regulatory subunit p85alpha .", "subunit p85alpha . gain", "p85alpha . gain of", ". gain of function", "of function mutations activate", "function mutations activate pi3k", "mutations activate pi3k signaling", "activate pi3k signaling by", "pi3k signaling by diverse", "signaling by diverse mechanisms.", "by diverse mechanisms. mutations", "diverse mechanisms. mutations affecting", "mechanisms. mutations affecting the", "mutations affecting the helical", "affecting the helical domain", "the helical domain of", "helical domain of pik3ca", "domain of pik3ca and", "of pik3ca and mutations", "pik3ca and mutations affecting", "and mutations affecting nsh2", "mutations affecting nsh2 and", "affecting nsh2 and ish2", "nsh2 and ish2 domains", "and ish2 domains of", "ish2 domains of pik3r1", "domains of pik3r1 impair", "of pik3r1 impair inhibitory", "pik3r1 impair inhibitory interactions", "impair inhibitory interactions between", "inhibitory interactions between these", "interactions between these two", "between these two subunits", "these two subunits while", "two subunits while preserving", "subunits while preserving their", "while preserving their association.", "preserving their association. mutations", "their association. mutations in", "association. mutations in the", "mutations in the catalytic", "in the catalytic domain", "the catalytic domain of", "catalytic domain of pik3ca", "domain of pik3ca enable", "of pik3ca enable the", "pik3ca enable the kinase", "enable the kinase to", "the kinase to achieve", "kinase to achieve an", "to achieve an active", "achieve an active conformation.", "an active conformation. pi3k", "active conformation. pi3k complexes", "conformation. pi3k complexes with", "pi3k complexes with gain", "complexes with gain of", "with gain of function", "of function mutations therefore", "function mutations therefore produce", "mutations therefore produce pip3", "therefore produce pip3 and", "produce pip3 and activate", "pip3 and activate downstream", "and activate downstream akt", "activate downstream akt in", "downstream akt in the", "akt in the absence", "in the absence of", "the absence of growth", "absence of growth factors", "growth factors huang", "factors huang et", "huang et al. 2007", "al. 2007 zhao", "2007 zhao et", "zhao et al. 2005", "al. 2005 miled", "2005 miled et", "miled et al. 2007", "al. 2007 horn", "2007 horn et", "horn et al. 2008", "al. 2008 sun", "2008 sun et", "sun et al. 2010", "al. 2010 jaiswal", "2010 jaiswal et", "jaiswal et al. 2009", "al. 2009 zhao", "2009 zhao and", "zhao and vogt 2010", "vogt 2010 urick", "2010 urick et", "urick et al. 2011", "et al. 2011 .", "signaling by pi3k/akt is frequently", "by pi3k/akt is frequently constitutively", "pi3k/akt is frequently constitutively activated", "is frequently constitutively activated in", "frequently constitutively activated in cancer", "constitutively activated in cancer via", "activated in cancer via gain", "in cancer via gain of", "cancer via gain of function", "via gain of function mutations", "gain of function mutations in", "of function mutations in one", "function mutations in one of", "mutations in one of the", "in one of the two", "one of the two pi3k", "of the two pi3k subunits", "pi3k subunits pi3kca", "pi3kca encoding the catalytic", "encoding the catalytic subunit p110alpha", "catalytic subunit p110alpha or", "subunit p110alpha or pik3r1", "or pik3r1 encoding the", "pik3r1 encoding the regulatory", "encoding the regulatory subunit p85alpha", "the regulatory subunit p85alpha .", "regulatory subunit p85alpha . gain", "subunit p85alpha . gain of", "p85alpha . gain of function", ". gain of function mutations", "gain of function mutations activate", "of function mutations activate pi3k", "function mutations activate pi3k signaling", "mutations activate pi3k signaling by", "activate pi3k signaling by diverse", "pi3k signaling by diverse mechanisms.", "signaling by diverse mechanisms. mutations", "by diverse mechanisms. mutations affecting", "diverse mechanisms. mutations affecting the", "mechanisms. mutations affecting the helical", "mutations affecting the helical domain", "affecting the helical domain of", "the helical domain of pik3ca", "helical domain of pik3ca and", "domain of pik3ca and mutations", "of pik3ca and mutations affecting", "pik3ca and mutations affecting nsh2", "and mutations affecting nsh2 and", "mutations affecting nsh2 and ish2", "affecting nsh2 and ish2 domains", "nsh2 and ish2 domains of", "and ish2 domains of pik3r1", "ish2 domains of pik3r1 impair", "domains of pik3r1 impair inhibitory", "of pik3r1 impair inhibitory interactions", "pik3r1 impair inhibitory interactions between", "impair inhibitory interactions between these", "inhibitory interactions between these two", "interactions between these two subunits", "between these two subunits while", "these two subunits while preserving", "two subunits while preserving their", "subunits while preserving their association.", "while preserving their association. mutations", "preserving their association. mutations in", "their association. mutations in the", "association. mutations in the catalytic", "mutations in the catalytic domain", "in the catalytic domain of", "the catalytic domain of pik3ca", "catalytic domain of pik3ca enable", "domain of pik3ca enable the", "of pik3ca enable the kinase", "pik3ca enable the kinase to", "enable the kinase to achieve", "the kinase to achieve an", "kinase to achieve an active", "to achieve an active conformation.", "achieve an active conformation. pi3k", "an active conformation. pi3k complexes", "active conformation. pi3k complexes with", "conformation. pi3k complexes with gain", "pi3k complexes with gain of", "complexes with gain of function", "with gain of function mutations", "gain of function mutations therefore", "of function mutations therefore produce", "function mutations therefore produce pip3", "mutations therefore produce pip3 and", "therefore produce pip3 and activate", "produce pip3 and activate downstream", "pip3 and activate downstream akt", "and activate downstream akt in", "activate downstream akt in the", "downstream akt in the absence", "akt in the absence of", "in the absence of growth", "the absence of growth factors", "of growth factors huang", "growth factors huang et", "factors huang et al.", "et al. 2007 zhao", "al. 2007 zhao et", "2007 zhao et al.", "et al. 2005 miled", "al. 2005 miled et", "2005 miled et al.", "et al. 2007 horn", "al. 2007 horn et", "2007 horn et al.", "et al. 2008 sun", "al. 2008 sun et", "2008 sun et al.", "et al. 2010 jaiswal", "al. 2010 jaiswal et", "2010 jaiswal et al.", "et al. 2009 zhao", "al. 2009 zhao and", "2009 zhao and vogt", "and vogt 2010 urick", "vogt 2010 urick et", "2010 urick et al.", "urick et al. 2011 ." ] }, { "record_id": "GLY_000594_1_228", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2424491", "r hsa", "hsa 2424491", "r hsa 2424491" ] }, { "record_id": "GLY_000594_1_228", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dap12 signaling", "in response", "response to", "to receptor", "receptor ligation", "the tyrosine", "tyrosine residues", "residues in", "in dap12's", "dap12's immunoreceptor", "immunoreceptor tyrosine", "tyrosine based", "based activation", "activation motif", "are phosphorylated", "phosphorylated by", "by src", "src family", "family kinases.", "kinases. these", "these phosphotyrosines", "phosphotyrosines form", "form the", "the docking", "docking site", "site for", "for the", "the protein", "protein tyrosine", "tyrosine kinase", "kinase syk", "syk in", "in myeloid", "myeloid cells", "cells and", "and syk", "syk and", "and zap70", "zap70 in", "in nk", "nk cells.", "cells. dap12", "dap12 bound", "bound syk", "syk autophosphorylates", "autophosphorylates and", "and phosphorylates", "phosphorylates the", "the scaffolding", "scaffolding molecule", "molecule lat", "recruiting the", "the proximal", "proximal signaling", "signaling molecules", "molecules phosphatidylinositol", "phosphatidylinositol 3", "3 oh", "oh kinase", "phospholipase c", "c gamma", "plc gamma", "grb2 related", "related adapter", "adapter downstream", "downstream of", "of shc", "sh2 domain", "domain containing", "containing leukocyte", "leukocyte protein", "protein of", "of 76", "76 kda", "growth factor", "factor receptor", "receptor bound", "bound protein", "protein 2:son", "2:son of", "of sevenless", "sevenless homolog", "homolog 1", "and vav.", "vav. all", "all of", "of these", "these intermediate", "intermediate signalling", "signalling molecules", "molecules result", "result in", "in the", "the recruitment", "recruitment and", "and activation", "activation of", "of kinases", "kinases akt", "casitas b", "b lineage", "lineage lymphoma", "and erk", "extracellular signal", "signal regulated", "regulated kinase", "and rearrangement", "rearrangement of", "of the", "the actin", "actin cytoskeleton", "actin polymerization", "finally leading", "leading to", "to cellular", "cellular activation.", "activation. plc", "gamma generates", "generates the", "the secondary", "secondary messengers", "messengers diacylglycerol", "and inositol", "inositol 1", "1 4", "4 5", "5 trisphosphate", "to activation", "of protein", "protein kinase", "kinase c", "and calcium", "calcium mobilization", "turnbull &", "& colonna", "colonna 2007", "klesney tait", "tait et", "et al.", "al. 2006", "2006 .", "in response to", "response to receptor", "to receptor ligation", "ligation the", "the tyrosine residues", "tyrosine residues in", "residues in dap12's", "in dap12's immunoreceptor", "dap12's immunoreceptor tyrosine", "immunoreceptor tyrosine based", "tyrosine based activation", "based activation motif", "motif itam", "itam are", "are phosphorylated by", "phosphorylated by src", "by src family", "src family kinases.", "family kinases. these", "kinases. these phosphotyrosines", "these phosphotyrosines form", "phosphotyrosines form the", "form the docking", "the docking site", "docking site for", "site for the", "for the protein", "the protein tyrosine", "protein tyrosine kinase", "tyrosine kinase syk", "kinase syk in", "syk in myeloid", "in myeloid cells", "myeloid cells and", "cells and syk", "and syk and", "syk and zap70", "and zap70 in", "zap70 in nk", "in nk cells.", "nk cells. dap12", "cells. dap12 bound", "dap12 bound syk", "bound syk autophosphorylates", "syk autophosphorylates and", "autophosphorylates and phosphorylates", "and phosphorylates the", "phosphorylates the scaffolding", "the scaffolding molecule", "scaffolding molecule lat", "lat recruiting", "recruiting the proximal", "the proximal signaling", "proximal signaling molecules", "signaling molecules phosphatidylinositol", "molecules phosphatidylinositol 3", "phosphatidylinositol 3 oh", "3 oh kinase", "kinase pi3k", "phospholipase c gamma", "gamma plc", "gads grb2", "grb2 related adapter", "related adapter downstream", "adapter downstream of", "downstream of shc", "slp76 sh2", "sh2 domain containing", "domain containing leukocyte", "containing leukocyte protein", "leukocyte protein of", "protein of 76", "of 76 kda", "grb2:sos growth", "growth factor receptor", "factor receptor bound", "receptor bound protein", "bound protein 2:son", "protein 2:son of", "2:son of sevenless", "of sevenless homolog", "sevenless homolog 1", "1 and", "and vav. all", "vav. all of", "all of these", "of these intermediate", "these intermediate signalling", "intermediate signalling molecules", "signalling molecules result", "molecules result in", "result in the", "in the recruitment", "the recruitment and", "recruitment and activation", "and activation of", "activation of kinases", "of kinases akt", "akt cbl", "cbl casitas", "casitas b lineage", "b lineage lymphoma", "lymphoma and", "erk extracellular", "extracellular signal regulated", "signal regulated kinase", "and rearrangement of", "rearrangement of the", "of the actin", "the actin cytoskeleton", "cytoskeleton actin", "polymerization finally", "finally leading to", "leading to cellular", "to cellular activation.", "cellular activation. plc", "activation. plc gamma", "plc gamma generates", "gamma generates the", "generates the secondary", "the secondary messengers", "secondary messengers diacylglycerol", "diacylglycerol dag", "dag and", "and inositol 1", "inositol 1 4", "1 4 5", "4 5 trisphosphate", "trisphosphate insp3", "leading to activation", "to activation of", "activation of protein", "of protein kinase", "protein kinase c", "c pkc", "pkc and", "and calcium mobilization", "mobilization respectively", "respectively turnbull", "turnbull & colonna", "& colonna 2007", "2007 klesney", "klesney tait et", "tait et al.", "et al. 2006", "al. 2006 .", "in response to receptor", "response to receptor ligation", "receptor ligation the", "ligation the tyrosine", "the tyrosine residues in", "tyrosine residues in dap12's", "residues in dap12's immunoreceptor", "in dap12's immunoreceptor tyrosine", "dap12's immunoreceptor tyrosine based", "immunoreceptor tyrosine based activation", "tyrosine based activation motif", "activation motif itam", "itam are phosphorylated", "are phosphorylated by src", "phosphorylated by src family", "by src family kinases.", "src family kinases. these", "family kinases. these phosphotyrosines", "kinases. these phosphotyrosines form", "these phosphotyrosines form the", "phosphotyrosines form the docking", "form the docking site", "the docking site for", "docking site for the", "site for the protein", "for the protein tyrosine", "the protein tyrosine kinase", "protein tyrosine kinase syk", "tyrosine kinase syk in", "kinase syk in myeloid", "syk in myeloid cells", "in myeloid cells and", "myeloid cells and syk", "cells and syk and", "and syk and zap70", "syk and zap70 in", "and zap70 in nk", "zap70 in nk cells.", "in nk cells. dap12", "nk cells. dap12 bound", "cells. dap12 bound syk", "dap12 bound syk autophosphorylates", "bound syk autophosphorylates and", "syk autophosphorylates and phosphorylates", "autophosphorylates and phosphorylates the", "and phosphorylates the scaffolding", "phosphorylates the scaffolding molecule", "the scaffolding molecule lat", "molecule lat recruiting", "lat recruiting the", "recruiting the proximal signaling", "the proximal signaling molecules", "proximal signaling molecules phosphatidylinositol", "signaling molecules phosphatidylinositol 3", "molecules phosphatidylinositol 3 oh", "phosphatidylinositol 3 oh kinase", "oh kinase pi3k", "pi3k phospholipase", "c gamma plc", "gamma plc gamma", "gamma gads", "gads grb2 related", "grb2 related adapter downstream", "related adapter downstream of", "adapter downstream of shc", "shc slp76", "slp76 sh2 domain", "sh2 domain containing leukocyte", "domain containing leukocyte protein", "containing leukocyte protein of", "leukocyte protein of 76", "protein of 76 kda", "kda grb2:sos", "grb2:sos growth factor", "growth factor receptor bound", "factor receptor bound protein", "receptor bound protein 2:son", "bound protein 2:son of", "protein 2:son of sevenless", "2:son of sevenless homolog", "of sevenless homolog 1", "homolog 1 and", "1 and vav.", "and vav. all of", "vav. all of these", "all of these intermediate", "of these intermediate signalling", "these intermediate signalling molecules", "intermediate signalling molecules result", "signalling molecules result in", "molecules result in the", "result in the recruitment", "in the recruitment and", "the recruitment and activation", "recruitment and activation of", "and activation of kinases", "activation of kinases akt", "kinases akt cbl", "cbl casitas b", "casitas b lineage lymphoma", "lineage lymphoma and", "lymphoma and erk", "and erk extracellular", "erk extracellular signal", "extracellular signal regulated kinase", "kinase and", "and rearrangement of the", "rearrangement of the actin", "of the actin cytoskeleton", "actin cytoskeleton actin", "cytoskeleton actin polymerization", "actin polymerization finally", "polymerization finally leading", "finally leading to cellular", "leading to cellular activation.", "to cellular activation. plc", "cellular activation. plc gamma", "activation. plc gamma generates", "plc gamma generates the", "gamma generates the secondary", "generates the secondary messengers", "the secondary messengers diacylglycerol", "messengers diacylglycerol dag", "dag and inositol", "and inositol 1 4", "inositol 1 4 5", "1 4 5 trisphosphate", "5 trisphosphate insp3", "insp3 leading", "leading to activation of", "to activation of protein", "activation of protein kinase", "of protein kinase c", "kinase c pkc", "pkc and calcium", "calcium mobilization respectively", "respectively turnbull &", "turnbull & colonna 2007", "colonna 2007 klesney", "2007 klesney tait", "klesney tait et al.", "tait et al. 2006", "et al. 2006 .", "in response to receptor ligation", "to receptor ligation the", "receptor ligation the tyrosine", "ligation the tyrosine residues", "the tyrosine residues in dap12's", "tyrosine residues in dap12's immunoreceptor", "residues in dap12's immunoreceptor tyrosine", "in dap12's immunoreceptor tyrosine based", "dap12's immunoreceptor tyrosine based activation", "immunoreceptor tyrosine based activation motif", "based activation motif itam", "motif itam are", "itam are phosphorylated by", "are phosphorylated by src family", "phosphorylated by src family kinases.", "by src family kinases. these", "src family kinases. these phosphotyrosines", "family kinases. these phosphotyrosines form", "kinases. these phosphotyrosines form the", "these phosphotyrosines form the docking", "phosphotyrosines form the docking site", "form the docking site for", "the docking site for the", "docking site for the protein", "site for the protein tyrosine", "for the protein tyrosine kinase", "the protein tyrosine kinase syk", "protein tyrosine kinase syk in", "tyrosine kinase syk in myeloid", "kinase syk in myeloid cells", "syk in myeloid cells and", "in myeloid cells and syk", "myeloid cells and syk and", "cells and syk and zap70", "and syk and zap70 in", "syk and zap70 in nk", "and zap70 in nk cells.", "zap70 in nk cells. dap12", "in nk cells. dap12 bound", "nk cells. dap12 bound syk", "cells. dap12 bound syk autophosphorylates", "dap12 bound syk autophosphorylates and", "bound syk autophosphorylates and phosphorylates", "syk autophosphorylates and phosphorylates the", "autophosphorylates and phosphorylates the scaffolding", "and phosphorylates the scaffolding molecule", "phosphorylates the scaffolding molecule lat", "scaffolding molecule lat recruiting", "molecule lat recruiting the", "lat recruiting the proximal", "recruiting the proximal signaling molecules", "the proximal signaling molecules phosphatidylinositol", "proximal signaling molecules phosphatidylinositol 3", "signaling molecules phosphatidylinositol 3 oh", "molecules phosphatidylinositol 3 oh kinase", "3 oh kinase pi3k", "pi3k phospholipase c", "phospholipase c gamma plc", "c gamma plc gamma", "plc gamma gads", "gads grb2 related adapter", "grb2 related adapter downstream of", "related adapter downstream of shc", "of shc slp76", "slp76 sh2 domain containing", "sh2 domain containing leukocyte protein", "domain containing leukocyte protein of", "containing leukocyte protein of 76", "leukocyte protein of 76 kda", "76 kda grb2:sos", "grb2:sos growth factor receptor", "growth factor receptor bound protein", "factor receptor bound protein 2:son", "receptor bound protein 2:son of", "bound protein 2:son of sevenless", "protein 2:son of sevenless homolog", "2:son of sevenless homolog 1", "sevenless homolog 1 and", "homolog 1 and vav.", "1 and vav. all", "and vav. all of these", "vav. all of these intermediate", "all of these intermediate signalling", "of these intermediate signalling molecules", "these intermediate signalling molecules result", "intermediate signalling molecules result in", "signalling molecules result in the", "molecules result in the recruitment", "result in the recruitment and", "in the recruitment and activation", "the recruitment and activation of", "recruitment and activation of kinases", "and activation of kinases akt", "of kinases akt cbl", "akt cbl casitas", "cbl casitas b lineage", "b lineage lymphoma and", "lineage lymphoma and erk", "and erk extracellular signal", "erk extracellular signal regulated", "regulated kinase and", "kinase and rearrangement", "and rearrangement of the actin", "rearrangement of the actin cytoskeleton", "the actin cytoskeleton actin", "actin cytoskeleton actin polymerization", "actin polymerization finally leading", "polymerization finally leading to", "finally leading to cellular activation.", "leading to cellular activation. plc", "to cellular activation. plc gamma", "cellular activation. plc gamma generates", "activation. plc gamma generates the", "plc gamma generates the secondary", "gamma generates the secondary messengers", "generates the secondary messengers diacylglycerol", "secondary messengers diacylglycerol dag", "diacylglycerol dag and", "dag and inositol 1", "and inositol 1 4 5", "inositol 1 4 5 trisphosphate", "4 5 trisphosphate insp3", "insp3 leading to", "leading to activation of protein", "to activation of protein kinase", "activation of protein kinase c", "protein kinase c pkc", "c pkc and", "pkc and calcium mobilization", "and calcium mobilization respectively", "mobilization respectively turnbull", "respectively turnbull & colonna", "& colonna 2007 klesney", "colonna 2007 klesney tait", "2007 klesney tait et", "klesney tait et al. 2006", "tait et al. 2006 ." ] }, { "record_id": "GLY_000594_1_229", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2426168", "r hsa", "hsa 2426168", "r hsa 2426168" ] }, { "record_id": "GLY_000594_1_229", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of gene", "gene expression", "expression by", "by srebf", "activation of gene", "of gene expression", "gene expression by", "expression by srebf", "srebf srebp", "activation of gene expression", "of gene expression by", "gene expression by srebf", "by srebf srebp", "activation of gene expression by", "of gene expression by srebf", "expression by srebf srebp", "after transiting", "transiting to", "to the", "the nucleus", "nucleus srebps", "bind short", "short sequences", "sterol regulatory", "regulatory elements", "in the", "the promoters", "promoters of", "of target", "target genes", "reviewed in", "in eberle", "eberle et", "et al.", "al. 2004", "weber et", "2004 .", ". srebps", "srebps alone", "alone are", "are relatively", "relatively weak", "weak activators", "activators 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promoters", "the promoters of", "promoters of target", "of target genes", "genes reviewed", "reviewed in eberle", "in eberle et", "eberle et al.", "et al. 2004", "2004 weber", "weber et al.", "al. 2004 .", "2004 . srebps", ". srebps alone", "srebps alone are", "alone are relatively", "are relatively weak", "relatively weak activators", "weak activators of", "activators of transcription", "transcription with", "with srebp1c being", "srebp1c being significantly", "being significantly weaker", "significantly weaker than", "weaker than srebp1a", "than srebp1a or", "srebp1a or srebp2.", "or srebp2. in", "srebp2. in combination", "in combination with", "combination with other", "with other transcription", "other transcription factors", "transcription factors such", "factors such as", "such as sp1", "as sp1 and", "sp1 and nf", "and nf y", "nf y the", "y the srebps", "the srebps are", "srebps are much", "are much stronger", "much stronger activators.", "stronger activators. srebp1c", 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reactions. they", "reactions. they also", "they also play", "also play important", "play important roles", "important roles in", "roles in inflammatory", "in inflammatory and", "inflammatory and immediate", "and immediate allergic", "immediate allergic reactions.", "allergic reactions. activation", "reactions. activation through", "activation through fceri", "through fceri bound", "fceri bound antigen", "bound antigen specific", "antigen specific ige", "specific ige causes", "ige causes release", "causes release of", "release of potent", "of potent inflammatory", "potent inflammatory mediators", "mediators such", "such as histamine", "histamine proteases", "proteases chemotactic", "factors cytokines", "cytokines and metabolites", "and metabolites of", "metabolites of arachidonic", "of arachidonic acid", "arachidonic acid that", "acid that act", "that act on", "act on the", "on the vasculature", "vasculature smooth", "muscle connective", "tissue mucous", "mucous glands and", "glands and inflammatory", "and inflammatory cells", "cells borish", "borish & joseph", "& joseph 1992", "1992 amin", "2012 metcalfe", "metcalfe et al.", "et al. 1993", "al. 1993 .", "1993 . fceri", ". fceri is", "fceri is a", "is a multimeric", "a multimeric cell", "multimeric cell surface", "cell surface receptor", "surface receptor that", "receptor that binds", "that binds the", "binds the fc", "the fc fragment", "fc fragment of", "fragment of ige", "of ige with", "ige with high", "with high affinity.", "high affinity. on", "affinity. on mast", "on mast cells", "mast cells and", "cells and basophils", "and basophils fceri", "basophils fceri exists", "fceri exists as", "exists as a", "as a tetrameric", "a tetrameric complex", "tetrameric complex consisting", "complex consisting of", "consisting of one", "of one alpha", "one alpha chain", "chain one", "one beta chain", "and two disulfide", "two disulfide bonded", "disulfide bonded gamma", "bonded gamma chains", "chains and", "and on dendritic", "on dendritic cells", "cells langerhans", "cells macrophages", "macrophages and", "and eosinophils it", "eosinophils it exists", "it exists as", "as a trimeric", "a trimeric complex", "trimeric complex with", "complex with one", "with one alpha", "alpha chain and", "chain and two", "chains wu", "2011 kraft", "kraft & kinet", "& kinet 2007", "kinet 2007 .", "2007 . fceri", ". fceri signaling", "fceri signaling in", "signaling in mast", "in mast cells", "mast cells includes", "cells includes a", "includes a network", "a network of", "network of signaling", "of signaling molecules", "signaling molecules and", "molecules and adaptor", "and adaptor proteins.", "adaptor proteins. these", "proteins. these molecules", "these molecules coordinate", "molecules coordinate ultimately", "coordinate ultimately leading", "ultimately leading to", "leading to effects", "to effects on", "effects on degranulation", "degranulation eicosanoid", "and cytokine and", "cytokine and chemokine", "and chemokine 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the", "and survival.
the first", "survival.
the first step", "first step in", "step in fceri", "in fceri signaling", "fceri signaling is", "signaling is the", "is the phosphorylation", "the phosphorylation of", "phosphorylation of the", "of the tyrosine", "the tyrosine residues", "tyrosine residues in", "residues in the", "in the itam", "the itam of", "itam of both", "of both the", "both the beta", "the beta and", "beta and the", "and the gamma", "the gamma subunits", "gamma subunits of", "subunits of the", "of the fceri", "the fceri by", "fceri by lyn", "lyn which", "which is bound", "is bound to", "bound to the", "to the fceri", "the fceri beta", "fceri beta chain.", "beta chain. the", "chain. the phosphorylated", "the phosphorylated itam", "phosphorylated itam then", "itam then recruits", "then recruits the", "recruits the protein", "the protein tyrosine", "protein tyrosine kinase", "tyrosine kinase syk", "syk spleen", "spleen tyrosine kinase", "kinase which", "which then phosphorylates", "then phosphorylates the", "phosphorylates the adaptor", "the adaptor protein", "adaptor protein lat.", "protein lat. phosphorylated", "lat. phosphorylated lat", "lat linker", "linker for activation", "for activation of", "activation of t", "of t cells", "cells acts", "acts as a", "as a scaffolding", "a scaffolding protein", "scaffolding protein and", "protein and recruits", "and recruits other", "recruits other cytosolic", "other cytosolic adaptor", "cytosolic adaptor molecules", "adaptor molecules grb2", "grb2 growth", "growth factor receptor", "factor receptor bound", "receptor bound protein", "bound protein 2", "gads grb2", "grb2 related adaptor", "related adaptor protein", "shc src", "src homology 2", "2 sh2", "domain containing transforming", "containing transforming protein", "transforming protein c", "c and", "slp76 sh2", "sh2 domain containing", "domain containing leukocyte", "containing leukocyte protein", "leukocyte protein of", "protein of 76", "of 76 kda", "as well as", "well as the", "as the 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histamine", "histamine release and", "release and cytokine", "and cytokine production.", "cytokine production. fceri", "production. fceri activation", "fceri activation also", "activation also triggers", "also triggers the", "triggers the phosphorylation", "phosphorylation of plc", "of plc gamma", "plc gamma which", "gamma which upon", "which upon membrane", "upon membrane localisation", "membrane localisation hydrolyse", "localisation hydrolyse pip2", "hydrolyse pip2 to", "pip2 to form", "to form ip3", "form ip3 and", "ip3 and 1", "and 1 2", "1 2 diacylglycerol", "diacylglycerol dag", "second messengers that", "messengers that release", "that release ca2+", "release ca2+ from", "ca2+ from internal", "from internal stores", "internal stores and", "stores and activate", "and activate pkc", "pkc respectively.", "respectively. degranulation or", "degranulation or histamine", "or histamine release", "histamine release follows", "release follows the", "follows the activation", "the activation of", "activation of plc", "plc gamma and", "gamma and protein", "and protein kinase", "protein kinase c", "c pkc", "pkc and", "and the increased", "the increased mobilization", "increased mobilization of", "mobilization of calcium", "calcium ca2+", "ca2+ . receptor", ". receptor aggregation", "receptor aggregation also", "aggregation also results", "also results in", "results in the", "in the phosphorylation", "phosphorylation of adaptor", "of adaptor protein", "adaptor protein ntal/lat2", "protein ntal/lat2 which", "ntal/lat2 which then", "which then recruits", "then recruits gab2.", "recruits gab2. pi3k", "gab2. pi3k associates", "pi3k associates with", "associates with phosphorylated", "with phosphorylated gab2", "phosphorylated gab2 and", "gab2 and catalyses", "and catalyses the", "catalyses the formation", "the formation of", "formation of pip3", "of pip3 in", "pip3 in the", "in the membrane", "membrane which", "which attracts many", "attracts many ph", "many ph domain", "ph domain proteins", "domain proteins like", "proteins like btk", "btk plc", "gamma akt", "akt and pdk.", "and pdk. pi3k", "pdk. pi3k mediated", "pi3k mediated activation", "mediated activation of", "activation of akt", "of akt then", "akt then regulate", "then regulate the", "regulate the mast", "the mast cell", "mast cell proliferation", "proliferation development", "development and survival", "survival gu", "gu et al.", "et al. 2001", "al. 2001 .", "mast cells mc", "mc are distributed", "are distributed in tissues", "distributed in tissues throughout", "in tissues throughout the", "tissues throughout the human", "throughout the human body", "the human body and", "human body and have", "body and have long", "and have long been", "have long been recognized", "long been recognized as", "been recognized as key", "recognized as key cells", "as key cells of", "key cells of type", "cells of type i", "of type i hypersensitivity", "type i hypersensitivity reactions.", "i hypersensitivity reactions. they", "hypersensitivity reactions. they also", "reactions. they also play", "they also play important", "also play important roles", "play important roles in", "important roles in inflammatory", "roles in inflammatory and", "in inflammatory and immediate", "inflammatory and immediate allergic", "and immediate allergic reactions.", "immediate allergic reactions. activation", "allergic reactions. activation through", "reactions. activation through fceri", "activation through fceri bound", "through fceri bound antigen", "fceri bound antigen specific", "bound antigen specific ige", "antigen specific ige causes", "specific ige causes release", "ige causes release of", "causes release of potent", "release of potent inflammatory", "of potent inflammatory mediators", "inflammatory mediators such", "mediators such as", "as histamine proteases", "proteases chemotactic factors", "chemotactic factors cytokines", "factors cytokines and", "cytokines and metabolites of", "and metabolites of arachidonic", "metabolites of arachidonic acid", "of arachidonic acid that", "arachidonic acid that act", "acid that act on", "that act on the", "act on the vasculature", "the vasculature smooth", "vasculature smooth muscle", "smooth muscle connective", "muscle connective tissue", "connective tissue mucous", "tissue mucous glands", "mucous glands and inflammatory", "glands and inflammatory cells", "inflammatory cells borish", "cells borish &", "borish & joseph 1992", "joseph 1992 amin", "1992 amin 2012", "amin 2012 metcalfe", "2012 metcalfe et", "metcalfe et al. 1993", "et al. 1993 .", "al. 1993 . fceri", "1993 . fceri is", ". fceri is a", "fceri is a multimeric", "is a multimeric cell", "a multimeric cell surface", "multimeric cell surface receptor", "cell surface receptor that", "surface receptor that binds", "receptor that binds the", "that binds the fc", "binds the fc fragment", "the fc fragment of", "fc fragment of ige", "fragment of ige with", "of ige with high", "ige with high affinity.", "with high affinity. on", "high affinity. on mast", "affinity. on mast cells", "on mast cells and", "mast cells and basophils", "cells and basophils fceri", "and basophils fceri exists", "basophils fceri exists as", "fceri exists as a", "exists as a tetrameric", "as a tetrameric complex", "a tetrameric complex consisting", "tetrameric complex consisting of", "complex consisting of one", "consisting of one alpha", "of one alpha chain", "alpha chain one", "chain one beta", "beta chain and", "and two disulfide bonded", "two disulfide bonded gamma", "disulfide bonded gamma chains", "gamma chains and", "chains and on", "and on dendritic cells", "dendritic cells langerhans", "cells langerhans cells", "langerhans cells macrophages", "macrophages and eosinophils", "and eosinophils it exists", "eosinophils it exists as", "it exists as a", "exists as a trimeric", "as a trimeric complex", "a trimeric complex with", "trimeric complex with one", "complex with one 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"eicosanoid production and", "production and cytokine", "and cytokine and chemokine", "cytokine and chemokine production", "and chemokine production and", "chemokine production and cell", "production and cell migration", "and cell migration and", "cell migration and adhesion", "and adhesion growth", "adhesion growth and", "growth and survival.
the first", "and survival.
the first step", "survival.
the first step in", "first step in fceri", "step in fceri signaling", "in fceri signaling is", "fceri signaling is the", "signaling is the phosphorylation", "is the phosphorylation of", "the phosphorylation of the", "phosphorylation of the tyrosine", "of the tyrosine residues", "the tyrosine residues in", "tyrosine residues in the", "residues in the itam", "in the itam of", "the itam of both", "itam of both the", "of both the beta", "both the beta and", "the beta and the", "beta and the gamma", "and the gamma subunits", "the gamma subunits of", "gamma subunits of the", "subunits of the fceri", "of the fceri by", "the fceri by lyn", "by lyn which", "lyn which is", "which is bound to", "is bound to the", "bound to the fceri", "to the fceri beta", "the fceri beta chain.", "fceri beta chain. the", "beta chain. the phosphorylated", "chain. the phosphorylated itam", "the phosphorylated itam then", "phosphorylated itam then recruits", "itam then recruits the", "then recruits the protein", "recruits the protein tyrosine", "the protein tyrosine kinase", "protein tyrosine kinase syk", "kinase syk spleen", "syk spleen tyrosine", "tyrosine kinase which", "kinase which then", "which then phosphorylates the", "then phosphorylates the adaptor", "phosphorylates the adaptor protein", "the adaptor protein lat.", "adaptor protein lat. phosphorylated", "protein lat. phosphorylated lat", "phosphorylated lat linker", "lat linker for", "linker for activation of", "for activation of t", "activation of t cells", "t cells acts", "cells acts as", "acts as a scaffolding", "as a scaffolding protein", "a scaffolding protein and", "scaffolding protein and recruits", "protein and recruits other", "and recruits other cytosolic", "recruits other cytosolic adaptor", "other cytosolic adaptor molecules", "cytosolic adaptor molecules grb2", "molecules grb2 growth", "grb2 growth factor", "growth factor receptor bound", "factor receptor bound protein", "receptor bound protein 2", "2 gads", "gads grb2 related", "grb2 related adaptor protein", "protein shc", "shc src homology", "homology 2 sh2", "domain containing transforming protein", "containing transforming protein c", "protein c and", "c and slp76", "and slp76 sh2", "slp76 sh2 domain", "sh2 domain containing leukocyte", "domain containing leukocyte protein", "containing leukocyte protein of", "leukocyte protein of 76", "protein of 76 kda", "kda as", "as well as the", "well as the exchange", "as the exchange factors", "the exchange factors and", "exchange factors and adaptor", "factors and adaptor molecules", "and adaptor molecules vav", "adaptor molecules vav and", "molecules vav and sos", "and sos son", "sos son of", "son of sevenless homologue", "homologue and", "and the signalling enzyme", "the signalling enzyme phospholipase", "signalling enzyme phospholipase c", "enzyme phospholipase c gamma1", "c gamma1 plc", "gamma1 plc gamma1", "plc gamma1 . tyrosoine", "gamma1 . tyrosoine phosphorylation", ". tyrosoine phosphorylation 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activation of", "the activation of plc", "activation of plc gamma", "of plc gamma and", "plc gamma and protein", "gamma and protein kinase", "and protein kinase c", "kinase c pkc", "pkc and the", "and the increased mobilization", "the increased mobilization of", "increased mobilization of calcium", "of calcium ca2+", "calcium ca2+ .", "ca2+ . receptor aggregation", ". receptor aggregation also", "receptor aggregation also results", "aggregation also results in", "also results in the", "results in the phosphorylation", "in the phosphorylation of", "the phosphorylation of adaptor", "phosphorylation of adaptor protein", "of adaptor protein ntal/lat2", "adaptor protein ntal/lat2 which", "protein ntal/lat2 which then", "ntal/lat2 which then recruits", "which then recruits gab2.", "then recruits gab2. pi3k", "recruits gab2. pi3k associates", "gab2. pi3k associates with", "pi3k associates with phosphorylated", "associates with phosphorylated gab2", "with phosphorylated gab2 and", "phosphorylated gab2 and catalyses", "gab2 and catalyses the", "and catalyses the formation", "catalyses the formation of", "the formation of pip3", "formation of pip3 in", "of pip3 in the", "pip3 in the membrane", "the membrane which", "membrane which attracts", "which attracts many ph", "attracts many ph domain", "many ph domain proteins", "ph domain proteins like", "domain proteins like btk", "like btk plc", "btk plc gamma", "plc gamma akt", "gamma akt and", "akt and pdk. pi3k", "and pdk. pi3k mediated", "pdk. pi3k mediated activation", "pi3k mediated activation of", "mediated activation of akt", "activation of akt then", "of akt then regulate", "akt then regulate the", "then regulate the mast", "regulate the mast cell", "the mast cell proliferation", "cell proliferation development", "proliferation development and", "and survival gu", "survival gu et", "gu et al. 2001", "et al. 2001 .", "cells mc are", "mc are distributed in", "are distributed in tissues throughout", "distributed in tissues throughout the", "in tissues throughout the human", "tissues throughout the human body", "throughout the human body and", "the human body and have", "human body and have long", "body and have long been", "and have long been recognized", "have long been recognized as", "long been recognized as key", "been recognized as key cells", "recognized as key cells of", "as key cells of type", "key cells of type i", "cells of type i hypersensitivity", "of type i hypersensitivity reactions.", "type i hypersensitivity reactions. they", "i hypersensitivity reactions. they also", "hypersensitivity reactions. they also play", "reactions. they also play important", "they also play important roles", "also play important roles in", "play important roles in inflammatory", "important roles in inflammatory and", "roles in inflammatory and immediate", "in inflammatory and immediate allergic", "inflammatory and immediate allergic reactions.", "and immediate allergic reactions. activation", "immediate allergic reactions. activation through", "allergic reactions. activation through fceri", "reactions. activation through fceri bound", "activation through fceri bound antigen", "through fceri bound antigen specific", "fceri bound antigen specific ige", "bound antigen specific ige causes", "antigen specific ige causes release", "specific ige causes release of", "ige causes release of potent", "causes release of potent inflammatory", "release of potent inflammatory mediators", "potent inflammatory mediators such", "inflammatory mediators such as", "mediators such as histamine", "such as histamine proteases", "histamine proteases chemotactic", "chemotactic factors cytokines and", "factors cytokines and metabolites", "cytokines and metabolites of arachidonic", "and metabolites of arachidonic acid", "metabolites of arachidonic acid that", "of arachidonic acid that act", "arachidonic acid that act on", "acid that act on the", "that act on the vasculature", "on the vasculature smooth", "the vasculature smooth muscle", "smooth muscle connective tissue", "connective tissue mucous glands", "tissue mucous glands and", "mucous glands and inflammatory cells", "and inflammatory cells borish", "inflammatory cells borish &", "cells borish & joseph", "& joseph 1992 amin", "joseph 1992 amin 2012", "amin 2012 metcalfe et", "2012 metcalfe et al.", "metcalfe et al. 1993 .", "et al. 1993 . fceri", "al. 1993 . fceri is", "1993 . fceri is a", ". fceri is a multimeric", "fceri is a multimeric cell", "is a multimeric cell surface", "a multimeric cell surface receptor", "multimeric cell surface receptor that", "cell surface receptor that binds", "surface receptor that binds the", "receptor that binds the fc", "that binds the fc fragment", "binds the fc fragment of", "the fc fragment of ige", "fc fragment of ige with", "fragment of ige with high", "of ige with high affinity.", "ige with high affinity. on", "with high affinity. on mast", "high affinity. on mast cells", "affinity. on mast cells and", "on mast cells and basophils", "mast cells and basophils fceri", "cells and basophils fceri exists", "and basophils fceri exists as", "basophils fceri exists as a", "fceri exists as a tetrameric", "exists as a tetrameric complex", "as a tetrameric complex consisting", "a tetrameric complex consisting of", "tetrameric complex consisting of one", "complex consisting of one alpha", "consisting of one alpha chain", "one alpha chain one", "alpha chain one beta", "chain one beta chain", "one beta chain and", "beta chain and two", "and two disulfide bonded gamma", "two disulfide bonded gamma chains", "bonded gamma chains and", "gamma chains and on", "chains and on dendritic", "on dendritic cells langerhans", "dendritic cells langerhans cells", "cells macrophages and", "macrophages and eosinophils it", "and eosinophils it exists as", "eosinophils it exists as a", "it exists as a trimeric", "exists as a trimeric complex", "as a trimeric complex with", "a trimeric complex 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ultimately leading", "molecules coordinate ultimately leading to", "coordinate ultimately leading to effects", "ultimately leading to effects on", "leading to effects on degranulation", "effects on degranulation eicosanoid", "on degranulation eicosanoid production", "eicosanoid production and cytokine", "production and cytokine and", "and cytokine and chemokine production", "cytokine and chemokine production and", "and chemokine production and cell", "chemokine production and cell migration", "production and cell migration and", "and cell migration and adhesion", "migration and adhesion growth", "and adhesion growth and", "adhesion growth and survival.
the", "growth and survival.
the first step", "and survival.
the first step in", "survival.
the first step in fceri", "first step in fceri signaling", "step in fceri signaling is", "in fceri signaling is the", "fceri signaling is the phosphorylation", "signaling is the phosphorylation of", "is the phosphorylation of the", "the phosphorylation of the tyrosine", "phosphorylation of the tyrosine residues", "of the tyrosine residues in", "the tyrosine residues in the", "tyrosine residues in the itam", "residues in the itam of", "in the itam of both", "the itam of both the", "itam of both the beta", "of both the beta and", "both the beta and the", "the beta and the gamma", "beta and the gamma subunits", "and the gamma subunits of", "the gamma subunits of the", "gamma subunits of the fceri", "subunits of the fceri by", "of the fceri by lyn", "fceri by lyn which", "by lyn which is", "lyn which is bound", "which is bound to the", "is bound to the fceri", "bound to the fceri beta", "to the fceri beta chain.", "the fceri beta chain. the", "fceri beta chain. the phosphorylated", "beta chain. the phosphorylated itam", "chain. the phosphorylated itam then", "the phosphorylated itam then recruits", "phosphorylated itam then recruits the", "itam then recruits the protein", "then recruits the protein tyrosine", "recruits the protein tyrosine kinase", "the protein tyrosine kinase syk", "tyrosine kinase syk spleen", "kinase syk spleen tyrosine", "syk spleen tyrosine kinase", "spleen tyrosine kinase which", "tyrosine kinase which then", "kinase which then phosphorylates", "which then phosphorylates the adaptor", "then phosphorylates the adaptor protein", "phosphorylates the adaptor protein lat.", "the adaptor protein lat. phosphorylated", "adaptor protein lat. phosphorylated lat", "lat. phosphorylated lat linker", "phosphorylated lat linker for", "lat linker for activation", "linker for activation of t", "for activation of t cells", "of t cells acts", "t cells acts as", "cells acts as a", "acts as a scaffolding protein", "as a scaffolding protein and", "a scaffolding protein and recruits", "scaffolding protein and recruits other", "protein and recruits other cytosolic", "and recruits other cytosolic adaptor", "recruits other cytosolic adaptor molecules", "other cytosolic adaptor molecules grb2", "adaptor molecules grb2 growth", "molecules grb2 growth factor", "grb2 growth factor receptor", "growth factor receptor bound protein", "factor receptor bound protein 2", "protein 2 gads", "gads grb2 related adaptor", "adaptor protein shc", "shc src homology 2", "src homology 2 sh2", "2 sh2 domain", "sh2 domain containing transforming", "domain containing transforming protein c", "transforming protein c and", "protein c and slp76", "and slp76 sh2 domain", "slp76 sh2 domain containing", "sh2 domain containing leukocyte protein", "domain containing leukocyte protein of", "containing leukocyte protein of 76", "leukocyte protein of 76 kda", "76 kda as", "kda as well", "as well as the exchange", "well as the exchange factors", "as the exchange factors and", "the exchange factors and adaptor", "exchange factors and adaptor molecules", "factors and adaptor molecules vav", "and adaptor molecules vav and", "adaptor molecules vav and sos", "vav and sos son", "and sos son of", "sos son of sevenless", "sevenless homologue and", "homologue and the", "and the signalling enzyme phospholipase", "the signalling enzyme phospholipase c", "signalling enzyme phospholipase c gamma1", "phospholipase c gamma1 plc", "c gamma1 plc gamma1", "gamma1 plc gamma1 .", "plc gamma1 . tyrosoine phosphorylation", "gamma1 . tyrosoine phosphorylation of", ". tyrosoine phosphorylation of enzymes", "tyrosoine phosphorylation of enzymes and", "phosphorylation of enzymes and adaptors", "enzymes and adaptors including", "and adaptors including vav", "including vav shc grb2", "vav shc grb2 and", "shc grb2 and sos stimulate", "grb2 and sos stimulate small", "and sos stimulate small gtpases", "sos stimulate small gtpases such", "stimulate small gtpases such as", "small gtpases such as rac", "such as rac ras", "as rac ras and", "rac ras and raf.", "ras and raf. these pathways", "and raf. these pathways lead", "raf. these pathways lead to", "these pathways lead to activation", "pathways lead to activation of", "lead to activation of the", "to activation of the erk", "of the erk jnk", "the erk jnk and", "erk jnk and p38", "jnk and p38 map kinases", "p38 map kinases histamine", "map kinases histamine release", "kinases histamine release and", "histamine release and cytokine production.", "release and cytokine production. fceri", "and cytokine production. fceri activation", "cytokine production. fceri activation also", "production. fceri activation also triggers", "fceri activation also triggers the", "activation also triggers the phosphorylation", "also triggers the phosphorylation of", "triggers the phosphorylation of plc", "the phosphorylation of plc gamma", "phosphorylation of plc gamma which", "of plc gamma which upon", "plc gamma which upon membrane", "gamma which upon membrane localisation", "which upon membrane localisation hydrolyse", "upon membrane localisation hydrolyse pip2", "membrane localisation hydrolyse pip2 to", "localisation hydrolyse pip2 to form", "hydrolyse pip2 to form ip3", "pip2 to form ip3 and", "to form ip3 and 1", "form ip3 and 1 2", "ip3 and 1 2 diacylglycerol", "1 2 diacylglycerol dag", "dag second", "second messengers that release ca2+", "messengers that release ca2+ from", "that release ca2+ from internal", "release ca2+ from internal stores", "ca2+ from internal stores and", "from internal stores and activate", "internal stores and activate pkc", "and activate pkc respectively.", "activate pkc respectively. degranulation", "pkc respectively. degranulation or", "respectively. degranulation or histamine release", "degranulation or histamine release follows", "or histamine release follows the", "histamine release follows the activation", "release follows the activation of", "follows the activation of plc", "the activation of plc gamma", "activation of plc gamma and", "of plc gamma and protein", "plc gamma and protein kinase", "gamma and protein kinase c", "protein kinase c pkc", "c pkc and", "pkc and the increased", "and the increased mobilization of", "the increased mobilization of calcium", "mobilization of calcium ca2+", "of calcium ca2+ .", "calcium ca2+ . receptor", "ca2+ . receptor aggregation also", ". receptor aggregation also results", "receptor aggregation also results in", "aggregation also results in the", "also results in the phosphorylation", "results in the phosphorylation of", "in the phosphorylation of adaptor", "the phosphorylation of adaptor protein", "phosphorylation of adaptor protein ntal/lat2", "of adaptor protein ntal/lat2 which", "adaptor protein ntal/lat2 which then", "protein ntal/lat2 which then recruits", "ntal/lat2 which then recruits gab2.", "which then recruits gab2. pi3k", "then recruits gab2. pi3k associates", "recruits gab2. pi3k associates with", "gab2. pi3k associates with phosphorylated", "pi3k associates with phosphorylated gab2", "associates with phosphorylated gab2 and", "with phosphorylated gab2 and catalyses", "phosphorylated gab2 and catalyses the", "gab2 and catalyses the formation", "and catalyses the formation of", "catalyses the formation of pip3", "the formation of pip3 in", "formation of pip3 in the", "of pip3 in the membrane", "in the membrane which", "the membrane which attracts", "membrane which attracts many", "which attracts many ph domain", "attracts many ph domain proteins", "many ph domain proteins like", "ph domain proteins like btk", "proteins like btk plc", "like btk plc gamma", "plc gamma akt and", "gamma akt and pdk.", "akt and pdk. pi3k mediated", "and pdk. pi3k mediated activation", "pdk. pi3k mediated activation of", "pi3k mediated activation of akt", "mediated activation of akt then", "activation of akt then regulate", "of akt then regulate the", "akt then regulate the mast", "then regulate the mast cell", "regulate the mast cell proliferation", "mast cell proliferation development", "cell proliferation development and", "proliferation development and survival", "development and survival gu", "and survival gu et", "survival gu et al.", "gu et al. 2001 ." ] }, { "record_id": "GLY_000594_1_233", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2467813", "r hsa", "hsa 2467813", "r hsa 2467813" ] }, { "record_id": "GLY_000594_1_233", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "separation of", "of sister", "sister chromatids", "separation of sister", "of sister chromatids", "separation of sister chromatids", "while sister", "chromatids resolve", "resolve in", "in prometaphase", "separating along", "along chromosomal", "chromosomal arms", "the cohesion", "cohesion of", "sister centromeres", "centromeres persists", "persists until", "until anaphase.", "anaphase. at", "at the", "the anaphase", "anaphase onset", "anaphase promoting", "promoting complex/cyclosome", "ubiquitinates pttg1", "targeting it", "it for", "for degradation", "hagting et", "et al.", "al. 2002", "2002 .", ". pttg1", "pttg1 acts", "acts as", "as an", "an inhibitor", "inhibitor of", "of espl1", "known as", "as separin", "separin i.e.", "i.e. separase", "separase .", ". hence", "pttg1 removal", "removal initiated", "initiated by", "by apc/c", "enables espl1", "espl1 to", "to become", "become catalytically", "catalytically active", "zou et", "al. 1999", "waizenegger et", ". espl1", "espl1 undergoes", "undergoes autoleavage", "and also", "also cleaves", "cleaves rad21", "rad21 subunit", "subunit of", "of centromeric", "centromeric cohesin", "hauf et", "al. 2001", "2001 .", ". rad21", "rad21 cleavage", "cleavage promotes", "promotes dissociation", "dissociation of", "of cohesin", "cohesin complexes", "complexes from", "from sister", "leading to", "to separation", "sister chromatids.", "chromatids. subsequent", "subsequent movement", "movement of", "chromatids to", "to opposite", "opposite poles", "poles of", "of the", "the mitotic", "mitotic spindle", "spindle segregates", "segregates replicated", "replicated chromosomes", "chromosomes to", "to two", "two daughter", "daughter cells", "al. 2000", "while sister chromatids", "sister chromatids resolve", "chromatids resolve in", "resolve in prometaphase", "prometaphase separating", "separating along chromosomal", "along chromosomal arms", "arms the", "the cohesion of", "cohesion of sister", "of sister centromeres", "sister centromeres persists", "centromeres persists until", "persists until anaphase.", "until anaphase. at", "anaphase. at the", "at the anaphase", "the anaphase onset", "onset the", "the anaphase promoting", "anaphase promoting complex/cyclosome", "complex/cyclosome apc/c", "apc/c ubiquitinates", "pttg1 securin", "targeting it for", "it for degradation", "degradation hagting", "hagting et al.", "et al. 2002", "al. 2002 .", "2002 . pttg1", ". pttg1 acts", "pttg1 acts as", "acts as an", "as an inhibitor", "an inhibitor of", "inhibitor of espl1", "espl1 known", "known as separin", "as separin i.e.", "separin i.e. separase", "i.e. separase .", "separase . hence", "hence pttg1", "pttg1 removal initiated", "removal initiated by", "initiated by apc/c", "apc/c enables", "enables espl1 to", "espl1 to become", "to become catalytically", "become catalytically active", "active zou", "zou et al.", "et al. 1999", "1999 waizenegger", "waizenegger et al.", "2002 . espl1", ". espl1 undergoes", "espl1 undergoes autoleavage", "autoleavage waizenegger", "2002 and", "and also cleaves", "also cleaves rad21", "cleaves rad21 subunit", "rad21 subunit of", "subunit of centromeric", "of centromeric cohesin", "cohesin hauf", "hauf et al.", "et al. 2001", "al. 2001 .", "2001 . rad21", ". rad21 cleavage", "rad21 cleavage promotes", "cleavage promotes dissociation", "promotes dissociation of", "dissociation of cohesin", "of cohesin complexes", "cohesin complexes from", "complexes from sister", "from sister centromeres", "centromeres leading", "leading to separation", "to separation of", "of sister chromatids.", "sister chromatids. subsequent", "chromatids. subsequent movement", "subsequent movement of", "movement of sister", "sister chromatids to", "chromatids to opposite", "to opposite poles", "opposite poles of", "poles of the", "of the mitotic", "the mitotic spindle", "mitotic spindle segregates", "spindle segregates replicated", "segregates replicated chromosomes", "replicated chromosomes to", "chromosomes to two", "to two daughter", "two daughter cells", "cells waizenegger", "et al. 2000", "2000 hauf", "2001 waizenegger", "while sister chromatids resolve", "sister chromatids resolve in", "chromatids resolve in prometaphase", "in prometaphase separating", "prometaphase separating along", "separating along chromosomal arms", "chromosomal arms the", "arms the cohesion", "the cohesion of sister", "cohesion of sister centromeres", "of sister centromeres persists", "sister centromeres persists until", "centromeres persists until anaphase.", "persists until anaphase. at", "until anaphase. at the", "anaphase. at the anaphase", "at the anaphase onset", "anaphase onset the", "onset the anaphase", "the anaphase promoting complex/cyclosome", "promoting complex/cyclosome apc/c", "apc/c ubiquitinates pttg1", "ubiquitinates pttg1 securin", "securin targeting", "targeting it for degradation", "for degradation hagting", "degradation hagting et", "hagting et al. 2002", "et al. 2002 .", "al. 2002 . pttg1", "2002 . pttg1 acts", ". pttg1 acts as", "pttg1 acts as an", "acts as an inhibitor", "as an inhibitor of", "an inhibitor of espl1", "of espl1 known", "espl1 known as", "known as separin i.e.", "as separin i.e. separase", "separin i.e. separase .", "i.e. separase . hence", ". hence pttg1", "hence pttg1 removal", "pttg1 removal initiated by", "removal initiated by apc/c", "by apc/c enables", "apc/c enables espl1", "enables espl1 to become", "espl1 to become catalytically", "to become catalytically active", "catalytically active zou", "active zou et", "zou et al. 1999", "al. 1999 waizenegger", "1999 waizenegger et", "waizenegger et al. 2002", "al. 2002 . espl1", "2002 . espl1 undergoes", ". espl1 undergoes autoleavage", "undergoes autoleavage waizenegger", "autoleavage waizenegger et", "al. 2002 and", "2002 and also", "and also cleaves rad21", "also cleaves rad21 subunit", "cleaves rad21 subunit of", "rad21 subunit of centromeric", "subunit of centromeric cohesin", "centromeric cohesin hauf", "cohesin hauf et", "hauf et al. 2001", "et al. 2001 .", "al. 2001 . rad21", "2001 . rad21 cleavage", ". rad21 cleavage promotes", "rad21 cleavage promotes dissociation", "cleavage promotes dissociation of", "promotes dissociation of cohesin", "dissociation of cohesin complexes", "of cohesin complexes from", "cohesin complexes from sister", "complexes from sister centromeres", "sister centromeres leading", "centromeres leading to", "leading to separation of", "to separation of sister", "separation of sister chromatids.", "of sister chromatids. subsequent", "sister chromatids. subsequent movement", "chromatids. subsequent movement of", "subsequent movement of sister", "movement of sister chromatids", "of sister chromatids to", "sister chromatids to opposite", "chromatids to opposite poles", "to opposite poles of", "opposite poles of the", "poles of the mitotic", "of the mitotic spindle", "the mitotic spindle segregates", "mitotic spindle segregates replicated", "spindle segregates replicated chromosomes", "segregates replicated chromosomes to", "replicated chromosomes to two", "chromosomes to two daughter", "to two daughter cells", "daughter cells waizenegger", "cells waizenegger et", "waizenegger et al. 2000", "al. 2000 hauf", "2000 hauf et", "al. 2001 waizenegger", "2001 waizenegger et", "while sister chromatids resolve in", "sister chromatids resolve in prometaphase", "resolve in prometaphase separating", "in prometaphase separating along", "prometaphase separating along chromosomal", "along chromosomal arms the", "chromosomal arms the cohesion", "arms the cohesion of", "the cohesion of sister centromeres", "cohesion of sister centromeres persists", "of sister centromeres persists until", "sister centromeres persists until anaphase.", "centromeres persists until anaphase. at", "persists until anaphase. at the", "until anaphase. at the anaphase", "anaphase. at the anaphase onset", "the anaphase onset the", "anaphase onset the anaphase", "onset the anaphase promoting", "anaphase promoting complex/cyclosome apc/c", "complex/cyclosome apc/c ubiquitinates", "securin targeting it", "it for degradation hagting", "for degradation hagting et", "degradation hagting et al.", "hagting et al. 2002 .", "et al. 2002 . pttg1", "al. 2002 . pttg1 acts", "2002 . pttg1 acts as", ". pttg1 acts as an", "pttg1 acts as an inhibitor", "acts as an inhibitor of", "as an inhibitor of espl1", "inhibitor of espl1 known", "of espl1 known as", "espl1 known as separin", "known as separin i.e. separase", "as separin i.e. separase .", "separin i.e. separase . hence", "separase . hence pttg1", ". hence pttg1 removal", "hence pttg1 removal initiated", "pttg1 removal initiated by apc/c", "initiated by apc/c enables", "by apc/c enables espl1", "apc/c enables espl1 to", "enables espl1 to become catalytically", "espl1 to become catalytically active", "become catalytically active zou", "catalytically active zou et", "active zou et al.", "et al. 1999 waizenegger", "al. 1999 waizenegger et", "1999 waizenegger et al.", "waizenegger et al. 2002 .", "et al. 2002 . espl1", "al. 2002 . espl1 undergoes", "2002 . espl1 undergoes autoleavage", "espl1 undergoes autoleavage waizenegger", "undergoes autoleavage waizenegger et", "autoleavage waizenegger et al.", "et al. 2002 and", "al. 2002 and also", "2002 and also cleaves", "and also cleaves rad21 subunit", "also cleaves rad21 subunit of", "cleaves rad21 subunit of centromeric", "rad21 subunit of centromeric cohesin", "of centromeric cohesin hauf", "centromeric cohesin hauf et", "cohesin hauf et al.", "hauf et al. 2001 .", "et al. 2001 . rad21", "al. 2001 . rad21 cleavage", "2001 . rad21 cleavage promotes", ". rad21 cleavage promotes dissociation", "rad21 cleavage promotes dissociation of", "cleavage promotes dissociation of cohesin", "promotes dissociation of cohesin complexes", "dissociation of cohesin complexes from", "of cohesin complexes from sister", "cohesin complexes from sister centromeres", "from sister centromeres leading", "sister centromeres leading to", "centromeres leading to separation", "leading to separation of sister", "to separation of sister chromatids.", "separation of sister chromatids. subsequent", "of sister chromatids. subsequent movement", "sister chromatids. subsequent movement of", "chromatids. subsequent movement of sister", "subsequent movement of sister chromatids", "movement of sister chromatids to", "of sister chromatids to opposite", "sister chromatids to opposite poles", "chromatids to opposite poles of", "to opposite poles of the", "opposite poles of the mitotic", "poles of the mitotic spindle", "of the mitotic spindle segregates", "the mitotic spindle segregates replicated", "mitotic spindle segregates replicated chromosomes", "spindle segregates replicated chromosomes to", "segregates replicated chromosomes to two", "replicated chromosomes to two daughter", "chromosomes to two daughter cells", "two daughter cells waizenegger", "daughter cells waizenegger et", "cells waizenegger et al.", "et al. 2000 hauf", "al. 2000 hauf et", "2000 hauf et al.", "et al. 2001 waizenegger", "al. 2001 waizenegger et", "2001 waizenegger et al." ] }, { "record_id": "GLY_000594_1_234", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2500257", "r hsa", "hsa 2500257", "r hsa 2500257" ] }, { "record_id": "GLY_000594_1_234", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of sister", "sister chromatid", "chromatid cohesion", "resolution of sister", "of sister chromatid", "sister chromatid cohesion", "resolution of sister chromatid", "of sister chromatid cohesion", "resolution of sister chromatid cohesion", "the resolution", "sister chromatids", "chromatids in", "in mitotic", "mitotic prometaphase", "prometaphase involves", "involves removal", "removal of", "of cohesin", "cohesin complexes", "complexes from", "from chromosomal", "chromosomal arms", "with preservation", "preservation of", "of cohesion", "cohesion at", "at centromeres", "losada et", "et al.", "al. 1998", "hauf et", "al. 2001", "al. 2005", "2005 .

cdk1", ".

cdk1 mediated", "mediated phosphorylation", "phosphorylation of", "cohesin bound", "bound cdca5", "at threonine", "threonine t159", "t159 provides", "provides a", "a docking", "docking site", "site for", "for plk1", "enabling plk1", "plk1 mediated", "cohesin subunits", "subunits stag2", "and rad21", "dreier et", "al. 2011", "zhang et", "2011 .", ". further", "further phosphorylation", "of cdca5", "cdca5 by", "by cdk1", "cdk1 results", "results in", "in dissociation", "dissociation of", "cdca5 from", "from cohesin", "cohesin complex", "which restores", "restores the", "the activity", "activity of", "of wapal", "wapal in", "in removing", "removing stag2", "stag2 phosphorylated", "phosphorylated cohesin", "cohesin from", "gandhi et", "al. 2006", "kueng et", "shintomi and", "and hirano", "hirano 2006", "nishiyama et", "al. 2010", "2011 .

at", ".

at centromeres", "kinetochore proteins", "proteins shugoshins", "sgol1 and", "and sgol2", "enable pp2a", "pp2a b56", "also a", "a kinetochore", "kinetochore constituent", "to dephosphorylate", "dephosphorylate the", "the stag2", "stag2 subunit", "subunit of", "of centromeric", "centromeric cohesin.", "cohesin. dephosphorylation", "dephosphorylation of", "of stag2", "stag2 enables", "enables maintenance", "maintenance of", "centromeric cohesion", "thus preventing", "preventing separation", "separation of", "chromatids until", "until anaphase", "salic et", "al. 2004", "kitajima et", "2006 .", "the resolution of", "of sister chromatids", "sister chromatids in", "chromatids in mitotic", "in mitotic prometaphase", "mitotic prometaphase involves", "prometaphase involves removal", "involves removal of", "removal of cohesin", "of cohesin complexes", "cohesin complexes from", "complexes from chromosomal", "from chromosomal arms", "arms with", "with preservation of", "preservation of cohesion", "of cohesion at", "cohesion at centromeres", "centromeres losada", "losada et al.", "et al. 1998", "1998 hauf", "hauf et al.", "et al. 2001", "2001 hauf", "et al. 2005", "al. 2005 .

cdk1", "2005 .

cdk1 mediated", ".

cdk1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of cohesin", "of cohesin bound", "cohesin bound cdca5", "cdca5 sororin", "sororin at", "at threonine t159", "threonine t159 provides", "t159 provides a", "provides a docking", "a docking site", "docking site for", "site for plk1", "plk1 enabling", "enabling plk1 mediated", "plk1 mediated phosphorylation", "of cohesin subunits", "cohesin subunits stag2", "stag2 sa2", "sa2 and", "rad21 hauf", "2005 dreier", "dreier et al.", "et al. 2011", "2011 zhang", "zhang et al.", "al. 2011 .", "2011 . further", ". further phosphorylation", "further phosphorylation of", "phosphorylation of cdca5", "of cdca5 by", "cdca5 by cdk1", "by cdk1 results", "cdk1 results in", "results in dissociation", "in dissociation of", "dissociation of cdca5", "of cdca5 from", "cdca5 from cohesin", "from cohesin complex", "complex which", "which restores the", "restores the activity", "the activity of", "activity of wapal", "of wapal in", "wapal in removing", "in removing stag2", "removing stag2 phosphorylated", "stag2 phosphorylated cohesin", "phosphorylated cohesin from", "cohesin from chromosomal", "arms hauf", "2005 gandhi", "gandhi et al.", "et al. 2006", "2006 kueng", "kueng et al.", "2006 shintomi", "shintomi and hirano", "and hirano 2006", "2006 nishiyama", "nishiyama et al.", "et al. 2010", "2010 zhang", "al. 2011 .

at", "2011 .

at centromeres", "centromeres kinetochore", "kinetochore proteins shugoshins", "shugoshins sgol1", "sgol1 and sgol2", "sgol2 enable", "enable pp2a b56", "b56 also", "also a kinetochore", "a kinetochore constituent", "constituent to", "to dephosphorylate the", "dephosphorylate the stag2", "the stag2 subunit", "stag2 subunit of", "subunit of centromeric", "of centromeric cohesin.", "centromeric cohesin. dephosphorylation", "cohesin. dephosphorylation of", "dephosphorylation of stag2", "of stag2 enables", "stag2 enables maintenance", "enables maintenance of", "maintenance of centromeric", "of centromeric cohesion", "cohesion thus", "thus preventing separation", "preventing separation of", "separation of sister", "sister chromatids until", "chromatids until anaphase", "anaphase salic", "salic et al.", "et al. 2004", "2004 kitajima", "kitajima et al.", "2005 kitajima", "al. 2006 .", "the resolution of sister", "resolution of sister chromatids", "of sister chromatids in", "sister chromatids in mitotic", "chromatids in mitotic prometaphase", "in mitotic prometaphase involves", "mitotic prometaphase involves removal", "prometaphase involves removal of", "involves removal of cohesin", "removal of cohesin complexes", "of cohesin complexes from", "cohesin complexes from chromosomal", "complexes from chromosomal arms", "chromosomal arms with", "arms with preservation", "with preservation of cohesion", "preservation of cohesion at", "of cohesion at centromeres", "at centromeres losada", "centromeres losada et", "losada et al. 1998", "al. 1998 hauf", "1998 hauf et", "hauf et al. 2001", "al. 2001 hauf", "2001 hauf et", "hauf et al. 2005", "et al. 2005 .

cdk1", "al. 2005 .

cdk1 mediated", "2005 .

cdk1 mediated phosphorylation", ".

cdk1 mediated phosphorylation of", "mediated phosphorylation of cohesin", "phosphorylation of cohesin bound", "of cohesin bound cdca5", "bound cdca5 sororin", "sororin at threonine", "at threonine t159 provides", "threonine t159 provides a", "t159 provides a docking", "provides a docking site", "a docking site for", "docking site for plk1", "for plk1 enabling", "plk1 enabling plk1", "enabling plk1 mediated phosphorylation", "plk1 mediated phosphorylation of", "phosphorylation of cohesin subunits", "of cohesin subunits stag2", "subunits stag2 sa2", "sa2 and rad21", "and rad21 hauf", "rad21 hauf et", "al. 2005 dreier", "2005 dreier et", "dreier et al. 2011", "al. 2011 zhang", "2011 zhang et", "zhang et al. 2011", "et al. 2011 .", "al. 2011 . further", "2011 . further phosphorylation", ". further phosphorylation of", "further phosphorylation of cdca5", "phosphorylation of cdca5 by", "of cdca5 by cdk1", "cdca5 by cdk1 results", "by cdk1 results in", "cdk1 results in dissociation", "results in dissociation of", "in dissociation of cdca5", "dissociation of cdca5 from", "of cdca5 from cohesin", "cdca5 from cohesin complex", "cohesin complex which", "complex which restores", "which restores the activity", "restores the activity of", "the activity of wapal", "activity of wapal in", "of wapal in removing", "wapal in removing stag2", "in removing stag2 phosphorylated", "removing stag2 phosphorylated cohesin", "stag2 phosphorylated cohesin from", "phosphorylated cohesin from chromosomal", "cohesin from chromosomal arms", "chromosomal arms hauf", "arms hauf et", "al. 2005 gandhi", "2005 gandhi et", "gandhi et al. 2006", "al. 2006 kueng", "2006 kueng et", "kueng et al. 2006", "al. 2006 shintomi", "2006 shintomi and", "shintomi and hirano 2006", "hirano 2006 nishiyama", "2006 nishiyama et", "nishiyama et al. 2010", "al. 2010 zhang", "2010 zhang et", "et al. 2011 .

at", "al. 2011 .

at centromeres", ".

at centromeres kinetochore", "centromeres kinetochore proteins", "proteins shugoshins sgol1", "shugoshins sgol1 and", "and sgol2 enable", "sgol2 enable pp2a", "pp2a b56 also", "b56 also a", "also a kinetochore constituent", "kinetochore constituent to", "constituent to dephosphorylate", "to dephosphorylate the stag2", "dephosphorylate the stag2 subunit", "the stag2 subunit of", "stag2 subunit of centromeric", "subunit of centromeric cohesin.", "of centromeric cohesin. dephosphorylation", "centromeric cohesin. dephosphorylation of", "cohesin. dephosphorylation of stag2", "dephosphorylation of stag2 enables", "of stag2 enables maintenance", "stag2 enables maintenance of", "enables maintenance of centromeric", "maintenance of centromeric cohesion", "centromeric cohesion thus", "cohesion thus preventing", "thus preventing separation of", "preventing separation of sister", "separation of sister chromatids", "of sister chromatids until", "sister chromatids until anaphase", "until anaphase salic", "anaphase salic et", "salic et al. 2004", "al. 2004 kitajima", "2004 kitajima et", "kitajima et al. 2004", "kitajima et al. 2005", "al. 2005 kitajima", "2005 kitajima et", "kitajima et al. 2006", "et al. 2006 .", "the resolution of sister chromatids", "resolution of sister chromatids in", "of sister chromatids in mitotic", "sister chromatids in mitotic prometaphase", "chromatids in mitotic prometaphase involves", "in mitotic prometaphase involves removal", "mitotic prometaphase involves removal of", "prometaphase involves removal of cohesin", "involves removal of cohesin complexes", "removal of cohesin complexes from", "of cohesin complexes from chromosomal", "cohesin complexes from chromosomal arms", "from chromosomal arms with", "chromosomal arms with preservation", "arms with preservation of", "with preservation of cohesion at", "preservation of cohesion at centromeres", "cohesion at centromeres losada", "at centromeres losada et", "centromeres losada et al.", "et al. 1998 hauf", "al. 1998 hauf et", "1998 hauf et al.", "et al. 2001 hauf", "al. 2001 hauf et", "2001 hauf et al.", "hauf et al. 2005 .

cdk1", "et al. 2005 .

cdk1 mediated", "al. 2005 .

cdk1 mediated phosphorylation", "2005 .

cdk1 mediated phosphorylation of", ".

cdk1 mediated phosphorylation of cohesin", "mediated phosphorylation of cohesin bound", "phosphorylation of cohesin bound cdca5", "cohesin bound cdca5 sororin", "cdca5 sororin at", "sororin at threonine t159", "at threonine t159 provides a", "threonine t159 provides a docking", "t159 provides a docking site", "provides a docking site for", "a docking site for plk1", "site for plk1 enabling", "for plk1 enabling plk1", "plk1 enabling plk1 mediated", "enabling plk1 mediated phosphorylation of", "plk1 mediated phosphorylation of cohesin", "mediated phosphorylation of cohesin subunits", "phosphorylation of cohesin subunits stag2", "cohesin subunits stag2 sa2", "stag2 sa2 and", "and rad21 hauf et", "rad21 hauf et al.", "et al. 2005 dreier", "al. 2005 dreier et", "2005 dreier et al.", "et al. 2011 zhang", "al. 2011 zhang et", "2011 zhang et al.", "zhang et al. 2011 .", "et al. 2011 . further", "al. 2011 . further phosphorylation", "2011 . further phosphorylation of", ". further phosphorylation of cdca5", "further phosphorylation of cdca5 by", "phosphorylation of cdca5 by cdk1", "of cdca5 by cdk1 results", "cdca5 by cdk1 results in", "by cdk1 results in dissociation", "cdk1 results in dissociation of", "results in dissociation of cdca5", "in dissociation of cdca5 from", "dissociation of cdca5 from cohesin", "of cdca5 from cohesin complex", "from cohesin complex which", "cohesin complex which restores", "complex which restores the", "which restores the activity of", "restores the activity of wapal", "the activity of wapal in", "activity of wapal in removing", "of wapal in removing stag2", "wapal in removing stag2 phosphorylated", "in removing stag2 phosphorylated cohesin", "removing stag2 phosphorylated cohesin from", "stag2 phosphorylated cohesin from chromosomal", "phosphorylated cohesin from chromosomal arms", "from chromosomal arms hauf", "chromosomal arms hauf et", "arms hauf et al.", "et al. 2005 gandhi", "al. 2005 gandhi et", "2005 gandhi et al.", "et al. 2006 kueng", "al. 2006 kueng et", "2006 kueng et al.", "et al. 2006 shintomi", "al. 2006 shintomi and", "2006 shintomi and hirano", "and hirano 2006 nishiyama", "hirano 2006 nishiyama et", "2006 nishiyama et al.", "et al. 2010 zhang", "al. 2010 zhang et", "2010 zhang et al.", "zhang et al. 2011 .

at", "et al. 2011 .

at centromeres", "2011 .

at centromeres kinetochore", ".

at centromeres kinetochore proteins", "centromeres kinetochore proteins shugoshins", "kinetochore proteins shugoshins sgol1", "proteins shugoshins sgol1 and", "shugoshins sgol1 and sgol2", "sgol1 and sgol2 enable", "and sgol2 enable pp2a", "sgol2 enable pp2a b56", "enable pp2a b56 also", "pp2a b56 also a", "b56 also a kinetochore", "a kinetochore constituent to", "kinetochore constituent to dephosphorylate", "constituent to dephosphorylate the", "to dephosphorylate the stag2 subunit", "dephosphorylate the stag2 subunit of", "the stag2 subunit of centromeric", "stag2 subunit of centromeric cohesin.", "subunit of centromeric cohesin. dephosphorylation", "of centromeric cohesin. dephosphorylation of", "centromeric cohesin. dephosphorylation of stag2", "cohesin. dephosphorylation of stag2 enables", "dephosphorylation of stag2 enables maintenance", "of stag2 enables maintenance of", "stag2 enables maintenance of centromeric", "enables maintenance of centromeric cohesion", "of centromeric cohesion thus", "centromeric cohesion thus preventing", "cohesion thus preventing separation", "thus preventing separation of sister", "preventing separation of sister chromatids", "separation of sister chromatids until", "of sister chromatids until anaphase", "chromatids until anaphase salic", "until anaphase salic et", "anaphase salic et al.", "et al. 2004 kitajima", "al. 2004 kitajima et", "2004 kitajima et al.", "et al. 2005 kitajima", "al. 2005 kitajima et", "2005 kitajima et al.", "kitajima et al. 2006 ." ] }, { "record_id": "GLY_000594_1_235", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2514859", "r hsa", "hsa 2514859", "r hsa 2514859" ] }, { "record_id": "GLY_000594_1_235", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "recovery and", "and regulation", "regulation of", "of the", "the phototransduction", "phototransduction cascade", "inactivation recovery", "recovery and regulation", "and regulation of", "regulation of the", "of the phototransduction", "the phototransduction cascade", "inactivation recovery and", "recovery and regulation of", "and regulation of the", "regulation of the phototransduction", "of the phototransduction cascade", "inactivation recovery and regulation", "recovery and regulation of the", "and regulation of the phototransduction", "regulation of the phototransduction cascade", "to terminate", "terminate the", "the single", "single photon", "photon response", "response and", "and restore", "restore the", "the system", "system to", "to its", "its basal", "basal state", "the three", "three activated", "activated intermediates", "intermediates in", "in phototransduction", "transducin alpha", "alpha subunit", "subunit with", "with gtp", "gtp bound", "gnat1 gtp", "and phosphodiesterase", "phosphodiesterase 6", "all need", "need to", "to be", "be efficiently", "efficiently deactivated.", "deactivated. in", "in addition", "the cgmp", "cgmp concentrations", "concentrations must", "must be", "be restored", "restored to", "to support", "support reopening", "reopening of", "the cng", "cng channels.", "channels. this", "this section", "section describes", "describes the", "the inactivation", "inactivation and", "and recovery", "recovery events", "events of", "the activated", "intermediates involved", "involved in", "burns &", "& pugh", "pugh 2010", "korenbrot 2012", "2012 .", "to terminate the", "terminate the single", "the single photon", "single photon response", "photon response and", "response and restore", "and restore the", "restore the system", "the system to", "system to its", "to its basal", "its basal state", "state the", "the three activated", "three activated intermediates", "activated intermediates in", "intermediates in phototransduction", "phototransduction rhodopsin", "rhodopsin mii", "transducin alpha subunit", "alpha subunit with", "subunit with gtp", "with gtp bound", "bound gnat1", "gtp and", "and phosphodiesterase 6", "6 pde6", "pde6 all", "all need to", "need to be", "to be efficiently", "be efficiently deactivated.", "efficiently deactivated. in", "deactivated. in addition", "addition the", "the cgmp concentrations", "cgmp concentrations must", "concentrations must be", "must be restored", "be restored to", "restored to support", "to support reopening", "support reopening of", "reopening of the", "of the cng", "the cng channels.", "cng channels. this", "channels. this section", "this section describes", "section describes the", "describes the inactivation", "the inactivation and", "inactivation and recovery", "and recovery events", "recovery events of", "events of the", "of the activated", "the activated intermediates", "activated intermediates involved", "intermediates involved in", "involved in phototransduction", "phototransduction burns", "burns & pugh", "& pugh 2010", "2010 korenbrot", "korenbrot 2012 .", "to terminate the single", "terminate the single photon", "the single photon response", "single photon response and", "photon response and restore", "response and restore the", "and restore the system", "restore the system to", "the system to its", "system to its basal", "to its basal state", "basal state the", "state the three", "the three activated intermediates", "three activated intermediates in", "activated intermediates in phototransduction", "in phototransduction rhodopsin", "mii transducin", "transducin alpha subunit with", "alpha subunit with gtp", "subunit with gtp bound", "gtp bound gnat1", "bound gnat1 gtp", "gnat1 gtp and", "gtp and phosphodiesterase", "phosphodiesterase 6 pde6", "pde6 all need", "all need to be", "need to be efficiently", "to be efficiently deactivated.", "be efficiently deactivated. in", "efficiently deactivated. in addition", "in addition the", "addition the cgmp", "the cgmp concentrations must", "cgmp concentrations must be", "concentrations must be restored", "must be restored to", "be restored to support", "restored to support reopening", "to support reopening of", "support reopening of the", "reopening of the cng", "of the cng channels.", "the cng channels. this", "cng channels. this section", "channels. this section describes", "this section describes the", "section describes the inactivation", "describes the inactivation and", "the inactivation and recovery", "inactivation and recovery events", "and recovery events of", "recovery events of the", "events of the activated", "of the activated intermediates", "the activated intermediates involved", "activated intermediates involved in", "intermediates involved in phototransduction", "in phototransduction burns", "phototransduction burns &", "burns & pugh 2010", "pugh 2010 korenbrot", "2010 korenbrot 2012", "to terminate the single photon", "terminate the single photon response", "the single photon response and", "single photon response and restore", "photon response and restore the", "response and restore the system", "and restore the system to", "restore the system to its", "the system to its basal", "system to its basal state", "its basal state the", "basal state the three", "state the three activated", "the three activated intermediates in", "three activated intermediates in phototransduction", "intermediates in phototransduction rhodopsin", "phototransduction rhodopsin mii", "mii transducin alpha", "transducin alpha subunit with gtp", "alpha subunit with gtp bound", "with gtp bound gnat1", "gtp bound gnat1 gtp", "gnat1 gtp and phosphodiesterase", "gtp and phosphodiesterase 6", "and phosphodiesterase 6 pde6", "6 pde6 all", "pde6 all need to", "all need to be efficiently", "need to be efficiently deactivated.", "to be efficiently deactivated. in", "be efficiently deactivated. in addition", "deactivated. in addition the", "in addition the cgmp", "addition the cgmp concentrations", "the cgmp concentrations must be", "cgmp concentrations must be restored", "concentrations must be restored to", "must be restored to support", "be restored to support reopening", "restored to support reopening of", "to support reopening of the", "support reopening of the cng", "reopening of the cng channels.", "of the cng channels. this", "the cng channels. this section", "cng channels. this section describes", "channels. this section describes the", "this section describes the inactivation", "section describes the inactivation and", "describes the inactivation and recovery", "the inactivation and recovery events", "inactivation and recovery events of", "and recovery events of the", "recovery events of the activated", "events of the activated intermediates", "of the activated intermediates involved", "the activated intermediates involved in", "activated intermediates involved in phototransduction", "involved in phototransduction burns", "in phototransduction burns &", "phototransduction burns & pugh", "& pugh 2010 korenbrot", "pugh 2010 korenbrot 2012", "2010 korenbrot 2012 ." ] }, { "record_id": "GLY_000594_1_236", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2559580", "r hsa", "hsa 2559580", "r hsa 2559580" ] }, { "record_id": "GLY_000594_1_236", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "oxidative stress", "stress induced", "induced senescence", "oxidative stress induced", "stress induced senescence", "oxidative stress induced senescence", "caused by", "by increased", "increased concentration", "concentration of", "of reactive", "reactive oxygen", "oxygen species", "in the", "the cell", "can happen", "happen as", "as a", "a consequence", "consequence of", "of mitochondrial", "mitochondrial dysfunction", "dysfunction induced", "induced by", "by the", "the oncogenic", "oncogenic ras", "moiseeva et", "et al.", "al. 2009", "or independent", "independent of", "of oncogenic", "oncogenic signaling.", "signaling. prolonged", "prolonged exposure", "exposure to", "to interferon", "interferon beta", "ifn beta", "also results", "results in", "in ros", "ros increase", "al. 2006", "2006 .", ". ros", "ros oxidize", "oxidize thioredoxin", "which causes", "causes txn", "txn to", "to dissociate", "dissociate from", "from the", "the n", "n terminus", "terminus of", "of map3k5", "enabling map3k5", "map3k5 to", "to become", "become catalytically", "catalytically active", "saitoh et", "al. 1998", "1998 .", "ros also", "also stimulate", "stimulate expression", "expression of", "of ste20", "ste20 family", "family kinases", "kinases mink1", "and tnik", "tnik through", "through an", "an unknown", "unknown mechanism", "and mink1", "mink1 and", "tnik positively", "positively regulate", "regulate map3k5", "map3k5 activation", "nicke et", "al. 2005", "2005 .

", ".


map3k5", "
map3k5 phosphorylates", "phosphorylates and", "and activates", "activates map2k3", "and map2k6", "ichijo et", "al. 1997", "takekawa et", "which act", "act as", "as p38", "p38 mapk", "mapk kinases", "as well", "well as", "as map2k4", "matsuura et", "al. 2002", "together with", "with map2k7", "acts as", "a jnk", "jnk kinase.

", "kinase.


mkk3", "
mkk3 and", "and mkk6", "mkk6 phosphorylate", "phosphorylate and", "and activate", "activate p38", "mapk alpha", "and beta", "raingeaud et", "al. 1996", "enabling p38", "p38 mapks", "mapks to", "to phosphorylate", "activate mapkapk2", "and mapkapk3", "ben levy", "levy et", "al. 1995", "clifton et", "mclaughlin et", "sithanandam et", "meng et", "lukas et", "al. 2004", "white et", "al. 2007", "as mapkapk5", "new et", "1998 and", "and 2003", "sun et", "2007 .

", ".


phosphorylation", "
phosphorylation of", "of jnks", "mapk9 and", "and mapk10", "by map3k5", "map3k5 activated", "activated map2k4", "deacon and", "and blank", "blank 1997", "fleming et", "al. 2000", "allows jnks", "jnks to", "to migrate", "migrate to", "to the", "the nucleus", "mizukami et", "where they", "they phosphorylate", "phosphorylate jun.", "jun. phosphorylated", "phosphorylated jun", "jun binds", "binds fos", "fos phosphorylated", "phosphorylated by", "by erk1", "erk1 or", "or erk2", "downstream of", "of activated", "activated ras", "okazaki and", "and sagata", "sagata 1995", "murphy et", "forming the", "the activated", "activated protein", "protein 1", "ap 1", "fos:jun heterodimer", "glover and", "and harrison", "harrison 1995", "ainbinder et", "1997 .", ".

", "


activation", "
activation of", "of p38", "mapks and", "and jnks", "jnks downstream", "ultimately converges", "converges on", "on transcriptional", "transcriptional regulation", "regulation of", "of cdkn2a", "cdkn2a locus.", "locus. in", "in dividing", "dividing cells", "nucleosomes bound", "bound to", "the cdkn2a", "cdkn2a locus", "locus are", "are trimethylated", "trimethylated on", "on lysine", "lysine residue", "residue 28", "28 of", "of histone", "histone h3", "the polycomb", "polycomb repressor", "repressor complex", "complex 2", "creating the", "the h3k27me3", "me3k 28", "28 hist1h3a", "bracken et", "kotake et", "2007 .", ". the", "the expression", "of polycomb", "polycomb constituents", "constituents of", "of prc2", "kuzmichev et", "eed and", "and suz12", "and thereby", "thereby formation", "formation of", "of the", "the prc2", "is positively", "positively regulated", "regulated in", "in growing", "growing cells", "cells by", "by e2f1", "e2f2 and", "and e2f3", "weinmann et", "al. 2001", "al. 2003", "2003 .", ". h3k27me3", "h3k27me3 mark", "mark serves", "serves as", "a docking", "docking site", "site for", "for the", "complex 1", "that contains", "contains bmi1", "and is", "is therefore", "therefore named", "named prc1.4", "leading to", "the repression", "repression of", "of transcription", "transcription of", "of p16ink4a", "p16ink4a and", "and p14arf", "p14arf from", "where pcr1.4", "pcr1.4 mediated", "mediated repression", "of p14arf", "p14arf transcription", "transcription in", "in humans", "humans may", "may be", "be context", "context dependent", "voncken et", "dietrich et", "agherbi et", "gao et", "al. 2012", "2012 .", ". mapkapk2", "mapkapk2 and", "activated downstream", "the map3k5", "map3k5 p38", "mapk cascade", "phosphorylate bmi1", "bmi1 of", "the prc1.4", "prc1.4 complex", "to dissociation", "dissociation of", "of prc1.4", "complex from", "locus and", "and upregulation", "upregulation of", "2005 .", ". ap", "1 transcription", "transcription factor", "formed as", "a result", "result of", "map3k5 jnk", "jnk signaling", "as ras", "ras signaling", "binds the", "the promoter", "promoter of", "of kdm6b", "gene and", "and stimulates", "stimulates kdm6b", "kdm6b expression.", "expression. kdm6b", "kdm6b is", "is a", "a histone", "histone demethylase", "demethylase that", "that removes", "removes h3k27me3", "mark i.e.", "i.e. demethylates", "demethylates lysine", "lysine k28", "k28 of", "of hist1h3a", "thereby preventing", "preventing prc1.4", "prc1.4 binding", "binding to", "and allowing", "allowing transcription", "agger et", "barradas et", "lin et", "2012 .

", ".


p16ink4a", "
p16ink4a inhibits", "inhibits phosphorylation", "phosphorylation mediated", "mediated inactivation", "inactivation of", "of rb", "rb family", "family members", "members by", "by cdk4", "cdk4 and", "and cdk6", "to cell", "cell cycle", "cycle arrest", "serrano et", "al. 1993", "1993 .", ". p14arf", "p14arf inhibits", "inhibits mdm2", "mdm2 mediated", "mediated degradation", "degradation of", "of tp53", "zhang et", "which also", "also contributes", "contributes to", "arrest in", "in cells", "cells undergoing", "undergoing oxidative", "oxidative stress.", "stress. in", "in addition", "phosphorylation of", "tp53 by", "by mapkapk5", "mapk signaling", "activates tp53", "tp53 and", "and contributes", "to cellular", "cellular senescence", "stress caused", "caused by increased", "by increased concentration", "increased concentration of", "concentration of reactive", "of reactive oxygen", "reactive oxygen species", "species ros", "ros in", "in the cell", "cell can", "can happen as", "happen as a", "as a consequence", "a consequence of", "consequence of mitochondrial", "of mitochondrial dysfunction", "mitochondrial dysfunction induced", "dysfunction induced by", "induced by the", "by the oncogenic", "the oncogenic ras", "ras moiseeva", "moiseeva et al.", "et al. 2009", "2009 or", "or independent of", "independent of oncogenic", "of oncogenic signaling.", "oncogenic signaling. prolonged", "signaling. prolonged exposure", "prolonged exposure to", "exposure to interferon", "to interferon beta", "beta ifnb", "ifnb ifn", "beta also", "also results in", "results in ros", "in ros increase", "increase moiseeva", "et al. 2006", "al. 2006 .", "2006 . ros", ". ros oxidize", "ros oxidize thioredoxin", "thioredoxin txn", "which causes txn", "causes txn to", "txn to dissociate", "to dissociate from", "dissociate from the", "from the n", "the n terminus", "n terminus of", "terminus of map3k5", "map3k5 ask1", "enabling map3k5 to", "map3k5 to become", "to become catalytically", "become catalytically active", "active saitoh", "saitoh et al.", "et al. 1998", "al. 1998 .", "1998 . ros", ". ros also", "ros also stimulate", "also stimulate expression", "stimulate expression of", "expression of ste20", "of ste20 family", "ste20 family kinases", "family kinases mink1", "mink1 mink", "mink and", "and tnik through", "tnik through an", "through an unknown", "an unknown mechanism", "mechanism and", "and mink1 and", "mink1 and tnik", "and tnik positively", "tnik positively regulate", "positively regulate map3k5", "regulate map3k5 activation", "activation nicke", "nicke et al.", "et al. 2005", "al. 2005 .

", "2005 .


map3k5", ".


map3k5 phosphorylates", "
map3k5 phosphorylates and", "phosphorylates and activates", "and activates map2k3", "map2k3 mkk3", "mkk3 and", "map2k6 mkk6", "ichijo et al.", "et al. 1997", "1997 takekawa", "takekawa et al.", "which act as", "act as p38", "as p38 mapk", "p38 mapk kinases", "kinases as", "as well as", "well as map2k4", "map2k4 sek1", "1997 matsuura", "matsuura et al.", "et al. 2002", "which together", "together with map2k7", "map2k7 mkk7", "acts as a", "as a jnk", "a jnk kinase.

", "jnk kinase.


mkk3", "kinase.


mkk3 and", "
mkk3 and mkk6", "and mkk6 phosphorylate", "mkk6 phosphorylate and", "phosphorylate and activate", "and activate p38", "activate p38 mapk", "p38 mapk alpha", "alpha mapk14", "mapk14 and", "beta mapk11", "raingeaud et al.", "et al. 1996", "enabling p38 mapks", "p38 mapks to", "mapks to phosphorylate", "to phosphorylate and", "and activate mapkapk2", "mapkapk2 mk2", "mk2 and", "mapkapk3 mk3", "ben levy et", "levy et al.", "et al. 1995", "1995 clifton", "clifton et al.", "1996 mclaughlin", "mclaughlin et al.", "1996 sithanandam", "sithanandam et al.", "1996 meng", "meng et al.", "2002 lukas", "lukas et al.", "et al. 2004", "2004 white", "white et al.", "et al. 2007", "well as mapkapk5", "mapkapk5 prak", "new et al.", "al. 1998 and", "1998 and 2003", "2003 sun", "sun et al.", "al. 2007 .

", "2007 .


phosphorylation", ".


phosphorylation of", "
phosphorylation of jnks", "jnks mapk8", "mapk8 mapk9", "mapk9 and mapk10", "mapk10 by", "by map3k5 activated", "map3k5 activated map2k4", "map2k4 deacon", "deacon and blank", "and blank 1997", "1997 fleming", "fleming et al.", "et al. 2000", "2000 allows", "allows jnks to", "jnks to migrate", "to migrate to", "migrate to the", "to the nucleus", "nucleus mizukami", "mizukami et al.", "1997 where", "where they phosphorylate", "they phosphorylate jun.", "phosphorylate jun. phosphorylated", "jun. phosphorylated jun", "phosphorylated jun binds", "jun binds fos", "binds fos phosphorylated", "fos phosphorylated by", "phosphorylated by erk1", "by erk1 or", "erk1 or erk2", "erk2 downstream", "downstream of activated", "of activated ras", "ras okazaki", "okazaki and sagata", "and sagata 1995", "1995 murphy", "murphy et al.", "forming the activated", "the activated protein", "activated protein 1", "1 ap", "1 complex", "complex fos:jun", "glover and harrison", "and harrison 1995", "1995 ainbinder", "ainbinder et al.", "al. 1997 .", "1997 .

", ".


activation", "


activation of", "
activation of p38", "of p38 mapks", "p38 mapks and", "mapks and jnks", "and jnks downstream", "jnks downstream of", "downstream of map3k5", "ask1 ultimately", "ultimately converges on", "converges on transcriptional", "on transcriptional regulation", "transcriptional regulation of", "regulation of cdkn2a", "of cdkn2a locus.", "cdkn2a locus. in", "locus. in dividing", "in dividing cells", "cells nucleosomes", "nucleosomes bound to", "bound to the", "to the cdkn2a", "the cdkn2a locus", "cdkn2a locus are", "locus are trimethylated", "are trimethylated on", "trimethylated on lysine", "on lysine residue", "lysine residue 28", "residue 28 of", "28 of histone", "of histone h3", "h3 hist1h3a", "hist1h3a by", "by the polycomb", "the polycomb repressor", "polycomb repressor complex", "repressor complex 2", "2 prc2", "creating the h3k27me3", "h3k27me3 me3k", "me3k 28 hist1h3a", "hist1h3a mark", "mark bracken", "bracken et al.", "2007 kotake", "kotake et al.", "al. 2007 .", "2007 . the", ". the expression", "the expression of", "expression of polycomb", "of polycomb constituents", "polycomb constituents of", "constituents of prc2", "prc2 kuzmichev", "kuzmichev et al.", "ezh2 eed", "eed and suz12", "and thereby formation", "thereby formation of", "formation of the", "of the prc2", "prc2 is", "is positively regulated", "positively regulated in", "regulated in growing", "in growing cells", "growing cells by", "cells by e2f1", "e2f1 e2f2", "e2f2 and e2f3", "e2f3 weinmann", "weinmann et al.", "et al. 2001", "2001 bracken", "et al. 2003", "al. 2003 .", "2003 . h3k27me3", ". h3k27me3 mark", "h3k27me3 mark serves", "mark serves as", "serves as a", "as a docking", "a docking site", "docking site for", "site for the", "for the polycomb", "repressor complex 1", "1 prc1", "prc1 that", "that contains bmi1", "bmi1 pcgf4", "pcgf4 and", "and is therefore", "is therefore named", "therefore named prc1.4", "prc1.4 leading", "leading to the", "to the repression", "the repression of", "repression of transcription", "of transcription of", "transcription of p16ink4a", "of p16ink4a and", "p16ink4a and p14arf", "and p14arf from", "p14arf from the", "from the cdkn2a", "locus where", "where pcr1.4 mediated", "pcr1.4 mediated repression", "mediated repression of", "repression of p14arf", "of p14arf transcription", "p14arf transcription in", "transcription in humans", "in humans may", "humans may be", "may be context", "be context dependent", "dependent voncken", "voncken et al.", "2005 dietrich", "dietrich et al.", "2007 agherbi", "agherbi et al.", "2009 gao", "gao et al.", "et al. 2012", "al. 2012 .", "2012 . mapkapk2", ". mapkapk2 and", "mapkapk2 and mapkapk3", "mapkapk3 activated", "activated downstream of", "downstream of the", "of the map3k5", "the map3k5 p38", "map3k5 p38 mapk", "p38 mapk cascade", "cascade phosphorylate", "phosphorylate bmi1 of", "bmi1 of the", "of the prc1.4", "the prc1.4 complex", "complex leading", "leading to dissociation", "to dissociation of", "dissociation of prc1.4", "of prc1.4 complex", "prc1.4 complex from", "complex from the", "cdkn2a locus and", "locus and upregulation", "and upregulation of", "upregulation of p14arf", "transcription voncken", "al. 2005 .", "2005 . ap", ". ap 1", "ap 1 transcription", "1 transcription factor", "factor formed", "formed as a", "as a result", "a result of", "result of map3k5", "of map3k5 jnk", "map3k5 jnk signaling", "signaling as", "well as ras", "as ras signaling", "signaling binds", "binds the promoter", "the promoter of", "promoter of kdm6b", "kdm6b jmjd3", "jmjd3 gene", "gene and stimulates", "and stimulates kdm6b", "stimulates kdm6b expression.", "kdm6b expression. kdm6b", "expression. kdm6b is", "kdm6b is a", "is a histone", "a histone demethylase", "histone demethylase that", "demethylase that removes", "that removes h3k27me3", "removes h3k27me3 mark", "h3k27me3 mark i.e.", "mark i.e. demethylates", "i.e. demethylates lysine", "demethylates lysine k28", "lysine k28 of", "k28 of hist1h3a", "hist1h3a thereby", "thereby preventing prc1.4", "preventing prc1.4 binding", "prc1.4 binding to", "binding to the", "locus and allowing", "and allowing transcription", "allowing transcription of", "p16ink4a agger", "agger et al.", "2009 barradas", "barradas et al.", "2009 lin", "lin et al.", "al. 2012 .

", "2012 .


p16ink4a", ".


p16ink4a inhibits", "
p16ink4a inhibits phosphorylation", "inhibits phosphorylation mediated", "phosphorylation mediated inactivation", "mediated inactivation of", "inactivation of rb", "of rb family", "rb family members", "family members by", "members by cdk4", "by cdk4 and", "cdk4 and cdk6", "cdk6 leading", "leading to cell", "to cell cycle", "cell cycle arrest", "arrest serrano", "serrano et al.", "et al. 1993", "al. 1993 .", "1993 . p14arf", ". p14arf inhibits", "p14arf inhibits mdm2", "inhibits mdm2 mediated", "mdm2 mediated degradation", "mediated degradation of", "degradation of tp53", "tp53 p53", "zhang et al.", "which also contributes", "also contributes to", "contributes to cell", "cycle arrest in", "arrest in cells", "in cells undergoing", "cells undergoing oxidative", "undergoing oxidative stress.", "oxidative stress. in", "stress. in addition", "addition phosphorylation", "phosphorylation of tp53", "of tp53 by", "tp53 by mapkapk5", "prak activated", "of map3k5 p38", "p38 mapk signaling", "signaling activates", "activates tp53 and", "tp53 and contributes", "and contributes to", "contributes to cellular", "to cellular senescence", "senescence sun", "oxidative stress caused", "stress caused by", "caused by increased concentration", "by increased concentration of", "increased concentration of reactive", "concentration of reactive oxygen", "of reactive oxygen species", "oxygen species ros", "ros in the", "the cell can", "cell can happen", "can happen as a", "happen as a consequence", "as a consequence of", "a consequence of mitochondrial", "consequence of mitochondrial dysfunction", "of mitochondrial dysfunction induced", "mitochondrial dysfunction induced by", "dysfunction induced by the", "induced by the oncogenic", "by the oncogenic ras", "oncogenic ras moiseeva", "ras moiseeva et", "moiseeva et al. 2009", "al. 2009 or", "2009 or independent", "or independent of oncogenic", "independent of oncogenic signaling.", "of oncogenic signaling. prolonged", "oncogenic signaling. prolonged exposure", "signaling. prolonged exposure to", "prolonged exposure to interferon", "exposure to interferon beta", "interferon beta ifnb", "ifnb ifn beta", "ifn beta also", "beta also results", "also results in ros", "results in ros increase", "ros increase moiseeva", "increase moiseeva et", "moiseeva et al. 2006", "et al. 2006 .", "al. 2006 . ros", "2006 . ros oxidize", ". ros oxidize thioredoxin", "oxidize thioredoxin txn", "txn which", "which causes txn to", "causes txn to dissociate", "txn to dissociate from", "to dissociate from the", "dissociate from the n", "from the n terminus", "the n terminus of", "n terminus of map3k5", "of map3k5 ask1", "ask1 enabling", "enabling map3k5 to become", "map3k5 to become catalytically", "to become catalytically active", "catalytically active saitoh", "active saitoh et", "saitoh et al. 1998", "et al. 1998 .", "al. 1998 . ros", "1998 . ros also", ". ros also stimulate", "ros also stimulate expression", "also stimulate expression of", "stimulate expression of ste20", "expression of ste20 family", "of ste20 family kinases", "ste20 family kinases mink1", "kinases mink1 mink", "mink and tnik", "and tnik through an", "tnik through an unknown", "through an unknown mechanism", "unknown mechanism and", "mechanism and mink1", "and mink1 and tnik", "mink1 and tnik positively", "and tnik positively regulate", "tnik positively regulate map3k5", "positively regulate map3k5 activation", "map3k5 activation nicke", "activation nicke et", "nicke et al. 2005", "et al. 2005 .

", "al. 2005 .


map3k5", "2005 .


map3k5 phosphorylates", ".


map3k5 phosphorylates and", "
map3k5 phosphorylates and activates", "phosphorylates and activates map2k3", "activates map2k3 mkk3", "mkk3 and map2k6", "and map2k6 mkk6", "mkk6 ichijo", "ichijo et al. 1997", "al. 1997 takekawa", "1997 takekawa et", "takekawa et al. 2005", "2005 which", "which act as p38", "act as p38 mapk", "as p38 mapk kinases", "mapk kinases as", "kinases as well", "as well as map2k4", "as map2k4 sek1", "sek1 ichijo", "al. 1997 matsuura", "1997 matsuura et", "matsuura et al. 2002", "2002 which", "which together with", "with map2k7 mkk7", "mkk7 acts", "acts as a jnk", "as a jnk kinase.

", "a jnk kinase.


mkk3", "jnk kinase.


mkk3 and", "kinase.


mkk3 and mkk6", "
mkk3 and mkk6 phosphorylate", "and mkk6 phosphorylate and", "mkk6 phosphorylate and activate", "phosphorylate and activate p38", "and activate p38 mapk", "activate p38 mapk alpha", "mapk alpha mapk14", "mapk14 and beta", "and beta mapk11", "mapk11 raingeaud", "raingeaud et al. 1996", "1996 enabling", "enabling p38 mapks to", "p38 mapks to phosphorylate", "mapks to phosphorylate and", "to phosphorylate and activate", "phosphorylate and activate mapkapk2", "activate mapkapk2 mk2", "mk2 and mapkapk3", "and mapkapk3 mk3", "mk3 ben", "ben levy et al.", "levy et al. 1995", "al. 1995 clifton", "1995 clifton et", "clifton et al. 1996", "al. 1996 mclaughlin", "1996 mclaughlin et", "mclaughlin et al. 1996", "al. 1996 sithanandam", "1996 sithanandam et", "sithanandam et al. 1996", "al. 1996 meng", "1996 meng et", "meng et al. 2002", "al. 2002 lukas", "2002 lukas et", "lukas et al. 2004", "al. 2004 white", "2004 white et", "white et al. 2007", "2007 as", "as well as mapkapk5", "as mapkapk5 prak", "prak new", "new et al. 1998", "et al. 1998 and", "al. 1998 and 2003", "and 2003 sun", "2003 sun et", "sun et al. 2007", "et al. 2007 .

", "al. 2007 .


phosphorylation", "2007 .


phosphorylation of", ".


phosphorylation of jnks", "of jnks mapk8", "mapk8 mapk9 and", "and mapk10 by", "mapk10 by map3k5", "by map3k5 activated map2k4", "activated map2k4 deacon", "map2k4 deacon and", "deacon and blank 1997", "blank 1997 fleming", "1997 fleming et", "fleming et al. 2000", "al. 2000 allows", "2000 allows jnks", "allows jnks to migrate", "jnks to migrate to", "to migrate to the", "migrate to the nucleus", "the nucleus mizukami", "nucleus mizukami et", "mizukami et al. 1997", "al. 1997 where", "1997 where they", "where they phosphorylate jun.", "they phosphorylate jun. phosphorylated", "phosphorylate jun. phosphorylated jun", "jun. phosphorylated jun binds", "phosphorylated jun binds fos", "jun binds fos phosphorylated", "binds fos phosphorylated by", "fos phosphorylated by erk1", "phosphorylated by erk1 or", "by erk1 or erk2", "or erk2 downstream", "erk2 downstream of", "downstream of activated ras", "activated ras okazaki", "ras okazaki and", "okazaki and sagata 1995", "sagata 1995 murphy", "1995 murphy et", "murphy et al. 2002", "2002 forming", "forming the activated protein", "the activated protein 1", "protein 1 ap", "1 ap 1", "ap 1 complex", "complex fos:jun heterodimer", "heterodimer glover", "glover and harrison 1995", "harrison 1995 ainbinder", "1995 ainbinder et", "ainbinder et al. 1997", "et al. 1997 .", "al. 1997 .

", "1997 .


activation", ".


activation of", "


activation of p38", "
activation of p38 mapks", "of p38 mapks and", "p38 mapks and jnks", "mapks and jnks downstream", "and jnks downstream of", "jnks downstream of map3k5", "ask1 ultimately converges", "ultimately converges on transcriptional", "converges on transcriptional regulation", "on transcriptional regulation of", "transcriptional regulation of cdkn2a", "regulation of cdkn2a locus.", "of cdkn2a locus. in", "cdkn2a locus. in dividing", "locus. in dividing cells", "dividing cells nucleosomes", "cells nucleosomes bound", "nucleosomes bound to the", "bound to the cdkn2a", "to the cdkn2a locus", "the cdkn2a locus are", "cdkn2a locus are trimethylated", "locus are trimethylated on", "are trimethylated on lysine", "trimethylated on lysine residue", "on lysine residue 28", "lysine residue 28 of", "residue 28 of histone", "28 of histone h3", "histone h3 hist1h3a", "hist1h3a by the", "by the polycomb repressor", "the polycomb repressor complex", "polycomb repressor complex 2", "complex 2 prc2", "prc2 creating", "the h3k27me3 me3k", "h3k27me3 me3k 28", "28 hist1h3a mark", "mark bracken et", "bracken et al. 2007", "al. 2007 kotake", "2007 kotake et", "kotake et al. 2007", "et al. 2007 .", "al. 2007 . the", "2007 . the expression", ". the expression of", "the expression of polycomb", "expression of polycomb constituents", "of polycomb constituents of", "polycomb constituents of prc2", "of prc2 kuzmichev", "prc2 kuzmichev et", "kuzmichev et al. 2002", "ezh2 eed and", "suz12 and", "and thereby formation of", "thereby formation of the", "formation of the prc2", "the prc2 is", "prc2 is positively", "is positively regulated in", "positively regulated in growing", "regulated in growing cells", "in growing cells by", "growing cells by e2f1", "by e2f1 e2f2", "e2f1 e2f2 and", "and e2f3 weinmann", "e2f3 weinmann et", "weinmann et al. 2001", "al. 2001 bracken", "2001 bracken et", "bracken et al. 2003", "et al. 2003 .", "al. 2003 . h3k27me3", "2003 . h3k27me3 mark", ". h3k27me3 mark serves", "h3k27me3 mark serves as", "mark serves as a", "serves as a docking", "as a docking site", "a docking site for", "docking site for the", "site for the polycomb", "for the polycomb repressor", "polycomb repressor complex 1", "complex 1 prc1", "prc1 that contains", "contains bmi1 pcgf4", "pcgf4 and is", "and is therefore named", "is therefore named prc1.4", "named prc1.4 leading", "prc1.4 leading to", "leading to the repression", "to the repression of", "the repression of transcription", "repression of transcription of", "of transcription of p16ink4a", "transcription of p16ink4a and", "of p16ink4a and p14arf", "p16ink4a and p14arf from", "and p14arf from the", "p14arf from the cdkn2a", "from the cdkn2a locus", "cdkn2a locus where", "locus where pcr1.4", "where pcr1.4 mediated repression", "pcr1.4 mediated repression of", "mediated repression of p14arf", "repression of p14arf transcription", "of p14arf transcription in", "p14arf transcription in humans", "transcription in humans may", "in humans may be", "humans may be context", "may be context dependent", "context dependent voncken", "dependent voncken et", "voncken et al. 2005", "al. 2005 dietrich", "2005 dietrich et", "dietrich et al. 2007", "al. 2007 agherbi", "2007 agherbi et", "agherbi et al. 2009", "al. 2009 gao", "2009 gao et", "gao et al. 2012", "et al. 2012 .", "al. 2012 . mapkapk2", "2012 . mapkapk2 and", ". mapkapk2 and mapkapk3", "and mapkapk3 activated", "mapkapk3 activated downstream", "activated downstream of the", "downstream of the map3k5", "of the map3k5 p38", "the map3k5 p38 mapk", "map3k5 p38 mapk cascade", "mapk cascade phosphorylate", "cascade phosphorylate bmi1", "phosphorylate bmi1 of the", "bmi1 of the prc1.4", "of the prc1.4 complex", "prc1.4 complex leading", "complex leading to", "leading to dissociation of", "to dissociation of prc1.4", "dissociation of prc1.4 complex", "of prc1.4 complex from", "prc1.4 complex from the", "complex from the cdkn2a", "the cdkn2a locus and", "cdkn2a locus and upregulation", "locus and upregulation of", "and upregulation of p14arf", "upregulation of p14arf transcription", "p14arf transcription voncken", "transcription voncken et", "et al. 2005 .", "al. 2005 . ap", "2005 . ap 1", ". ap 1 transcription", "ap 1 transcription factor", "transcription factor formed", "factor formed as", "formed as a result", "as a result of", "a result of map3k5", "result of map3k5 jnk", "of map3k5 jnk signaling", "jnk signaling as", "signaling as well", "as well as ras", "well as ras signaling", "ras signaling binds", "signaling binds the", "binds the promoter of", "the promoter of kdm6b", "of kdm6b jmjd3", "jmjd3 gene and", "gene and stimulates kdm6b", "and stimulates kdm6b expression.", "stimulates kdm6b expression. kdm6b", "kdm6b expression. kdm6b is", "expression. kdm6b is a", "kdm6b is a histone", "is a histone demethylase", "a histone demethylase that", "histone demethylase that removes", "demethylase that removes h3k27me3", "that removes h3k27me3 mark", "removes h3k27me3 mark i.e.", "h3k27me3 mark i.e. demethylates", "mark i.e. demethylates lysine", "i.e. demethylates lysine k28", "demethylates lysine k28 of", "lysine k28 of hist1h3a", "of hist1h3a thereby", "hist1h3a thereby preventing", "thereby preventing prc1.4 binding", "preventing prc1.4 binding to", "prc1.4 binding to the", "binding to the cdkn2a", "cdkn2a locus and allowing", "locus and allowing transcription", "and allowing transcription of", "allowing transcription of p16ink4a", "of p16ink4a agger", "p16ink4a agger et", "agger et al. 2009", "al. 2009 barradas", "2009 barradas et", "barradas et al. 2009", "al. 2009 lin", "2009 lin et", "lin et al. 2012", "et al. 2012 .

", "al. 2012 .


p16ink4a", "2012 .


p16ink4a inhibits", ".


p16ink4a inhibits phosphorylation", "
p16ink4a inhibits phosphorylation mediated", "inhibits phosphorylation mediated inactivation", "phosphorylation mediated inactivation of", "mediated inactivation of rb", "inactivation of rb family", "of rb family members", "rb family members by", "family members by cdk4", "members by cdk4 and", "by cdk4 and cdk6", "and cdk6 leading", "cdk6 leading to", "leading to cell cycle", "to cell cycle arrest", "cycle arrest serrano", "arrest serrano et", "serrano et al. 1993", "et al. 1993 .", "al. 1993 . p14arf", "1993 . p14arf inhibits", ". p14arf inhibits mdm2", "p14arf inhibits mdm2 mediated", "inhibits mdm2 mediated degradation", "mdm2 mediated degradation of", "mediated degradation of tp53", "of tp53 p53", "p53 zhang", "zhang et al. 1998", "1998 which", "which also contributes to", "also contributes to cell", "contributes to cell cycle", "cell cycle arrest in", "cycle arrest in cells", "arrest in cells undergoing", "in cells undergoing oxidative", "cells undergoing oxidative stress.", "undergoing oxidative stress. in", "oxidative stress. in addition", "in addition phosphorylation", "addition phosphorylation of", "phosphorylation of tp53 by", "of tp53 by mapkapk5", "by mapkapk5 prak", "prak activated downstream", "activated downstream of map3k5", "downstream of map3k5 p38", "of map3k5 p38 mapk", "map3k5 p38 mapk signaling", "mapk signaling activates", "signaling activates tp53", "activates tp53 and contributes", "tp53 and contributes to", "and contributes to cellular", "contributes to cellular senescence", "cellular senescence sun", "senescence sun et", "oxidative stress caused by", "stress caused by increased", "caused by increased concentration of", "by increased concentration of reactive", "increased concentration of reactive oxygen", "concentration of reactive oxygen species", "reactive oxygen species ros", "species ros in", "ros in the cell", "in the cell can", "the cell can happen", "cell can happen as", "can happen as a consequence", "happen as a consequence of", "as a consequence of mitochondrial", "a consequence of mitochondrial dysfunction", "consequence of mitochondrial dysfunction induced", "of mitochondrial dysfunction induced by", "mitochondrial dysfunction induced by the", "dysfunction induced by the oncogenic", "induced by the oncogenic ras", "the oncogenic ras moiseeva", "oncogenic ras moiseeva et", "ras moiseeva et al.", "et al. 2009 or", "al. 2009 or independent", "2009 or independent of", "or independent of oncogenic signaling.", "independent of oncogenic signaling. prolonged", "of oncogenic signaling. prolonged exposure", "oncogenic signaling. prolonged exposure to", "signaling. prolonged exposure to interferon", "prolonged exposure to interferon beta", "to interferon beta ifnb", "beta ifnb ifn", "ifn beta also results", "beta also results in", "also results in ros increase", "in ros increase moiseeva", "ros increase moiseeva et", "increase moiseeva et al.", "moiseeva et al. 2006 .", "et al. 2006 . ros", "al. 2006 . ros oxidize", "2006 . ros oxidize thioredoxin", "ros oxidize thioredoxin txn", "txn which causes", "which causes txn to dissociate", "causes txn to dissociate from", "txn to dissociate from the", "to dissociate from the n", "dissociate from the n terminus", "from the n terminus of", "the n terminus of map3k5", "terminus of map3k5 ask1", "ask1 enabling map3k5", "enabling map3k5 to become catalytically", "map3k5 to become catalytically active", "become catalytically active saitoh", "catalytically active saitoh et", "active saitoh et al.", "saitoh et al. 1998 .", "et al. 1998 . ros", "al. 1998 . ros also", "1998 . ros also stimulate", ". ros also stimulate expression", "ros also stimulate expression of", "also stimulate expression of ste20", "stimulate expression of ste20 family", "expression of ste20 family kinases", "of ste20 family kinases mink1", "family kinases mink1 mink", "mink1 mink and", "mink and tnik through", "and tnik through an unknown", "tnik through an unknown mechanism", "an unknown mechanism and", "unknown mechanism and mink1", "mechanism and mink1 and", "and mink1 and tnik positively", "mink1 and tnik positively regulate", "and tnik positively regulate map3k5", "tnik positively regulate map3k5 activation", "regulate map3k5 activation nicke", "map3k5 activation nicke et", "activation nicke et al.", "nicke et al. 2005 .

", "et al. 2005 .


map3k5", "al. 2005 .


map3k5 phosphorylates", "2005 .


map3k5 phosphorylates and", ".


map3k5 phosphorylates and activates", "
map3k5 phosphorylates and activates map2k3", "and activates map2k3 mkk3", "map2k3 mkk3 and", "mkk6 ichijo et", "et al. 1997 takekawa", "al. 1997 takekawa et", "1997 takekawa et al.", "al. 2005 which", "2005 which act", "which act as p38 mapk", "act as p38 mapk kinases", "p38 mapk kinases as", "mapk kinases as well", "kinases as well as", "well as map2k4 sek1", "sek1 ichijo et", "et al. 1997 matsuura", "al. 1997 matsuura et", "1997 matsuura et al.", "al. 2002 which", "which together with map2k7", "together with map2k7 mkk7", "mkk7 acts as", "acts as a jnk kinase.

", "as a jnk kinase.


mkk3", "a jnk kinase.


mkk3 and", "jnk kinase.


mkk3 and mkk6", "kinase.


mkk3 and mkk6 phosphorylate", "
mkk3 and mkk6 phosphorylate and", "and mkk6 phosphorylate and activate", "mkk6 phosphorylate and activate p38", "phosphorylate and activate p38 mapk", "and activate p38 mapk alpha", "p38 mapk alpha mapk14", "alpha mapk14 and", "mapk11 raingeaud et", "al. 1996 enabling", "1996 enabling p38", "enabling p38 mapks to phosphorylate", "p38 mapks to phosphorylate and", "mapks to phosphorylate and activate", "to phosphorylate and activate mapkapk2", "and activate mapkapk2 mk2", "mapkapk2 mk2 and", "mk3 ben levy", "ben levy et al. 1995", "et al. 1995 clifton", "al. 1995 clifton et", "1995 clifton et al.", "et al. 1996 mclaughlin", "al. 1996 mclaughlin et", "1996 mclaughlin et al.", "et al. 1996 sithanandam", "al. 1996 sithanandam et", "1996 sithanandam et al.", "et al. 1996 meng", "al. 1996 meng et", "1996 meng et al.", "et al. 2002 lukas", "al. 2002 lukas et", "2002 lukas et al.", "et al. 2004 white", "al. 2004 white et", "2004 white et al.", "al. 2007 as", "2007 as well", "well as mapkapk5 prak", "prak new et", "new et al. 1998 and", "et al. 1998 and 2003", "1998 and 2003 sun", "and 2003 sun et", "2003 sun et al.", "sun et al. 2007 .

", "et al. 2007 .


phosphorylation", "al. 2007 .


phosphorylation of", "2007 .


phosphorylation of jnks", "
phosphorylation of jnks mapk8", "jnks mapk8 mapk9", "mapk8 mapk9 and mapk10", "mapk9 and mapk10 by", "and mapk10 by map3k5", "mapk10 by map3k5 activated", "map3k5 activated map2k4 deacon", "activated map2k4 deacon and", "map2k4 deacon and blank", "and blank 1997 fleming", "blank 1997 fleming et", "1997 fleming et al.", "et al. 2000 allows", "al. 2000 allows jnks", "2000 allows jnks to", "allows jnks to migrate to", "jnks to migrate to the", "to migrate to the nucleus", "to the nucleus mizukami", "the nucleus mizukami et", "nucleus mizukami et al.", "et al. 1997 where", "al. 1997 where they", "1997 where they phosphorylate", "where they phosphorylate jun. phosphorylated", "they phosphorylate jun. phosphorylated jun", "phosphorylate jun. phosphorylated jun binds", "jun. phosphorylated jun binds fos", "phosphorylated jun binds fos phosphorylated", "jun binds fos phosphorylated by", "binds fos phosphorylated by erk1", "fos phosphorylated by erk1 or", "phosphorylated by erk1 or erk2", "erk1 or erk2 downstream", "or erk2 downstream of", "erk2 downstream of activated", "of activated ras okazaki", "activated ras okazaki and", "ras okazaki and sagata", "and sagata 1995 murphy", "sagata 1995 murphy et", "1995 murphy et al.", "al. 2002 forming", "2002 forming the", "forming the activated protein 1", "activated protein 1 ap", "protein 1 ap 1", "1 complex fos:jun", "fos:jun heterodimer glover", "heterodimer glover and", "and harrison 1995 ainbinder", "harrison 1995 ainbinder et", "1995 ainbinder et al.", "ainbinder et al. 1997 .", "et al. 1997 .

", "al. 1997 .


activation", "1997 .


activation of", ".


activation of p38", "


activation of p38 mapks", "
activation of p38 mapks and", "of p38 mapks and jnks", "p38 mapks and jnks downstream", "mapks and jnks downstream of", "and jnks downstream of map3k5", "downstream of map3k5 ask1", "map3k5 ask1 ultimately", "ask1 ultimately converges on", "ultimately converges on transcriptional regulation", "converges on transcriptional regulation of", "on transcriptional regulation of cdkn2a", "transcriptional regulation of cdkn2a locus.", "regulation of cdkn2a locus. in", "of cdkn2a locus. in dividing", "cdkn2a locus. in dividing cells", "in dividing cells nucleosomes", "dividing cells nucleosomes bound", "cells nucleosomes bound to", "nucleosomes bound to the cdkn2a", "bound to the cdkn2a locus", "to the cdkn2a locus are", "the cdkn2a locus are trimethylated", "cdkn2a locus are trimethylated on", "locus are trimethylated on lysine", "are trimethylated on lysine residue", "trimethylated on lysine residue 28", "on lysine residue 28 of", "lysine residue 28 of histone", "residue 28 of histone h3", "of histone h3 hist1h3a", "h3 hist1h3a by", "hist1h3a by the polycomb", "by the polycomb repressor complex", "the polycomb repressor complex 2", "repressor complex 2 prc2", "prc2 creating the", "creating the h3k27me3 me3k", "the h3k27me3 me3k 28", "h3k27me3 me3k 28 hist1h3a", "me3k 28 hist1h3a mark", "hist1h3a mark bracken", "mark bracken et al.", "et al. 2007 kotake", "al. 2007 kotake et", "2007 kotake et al.", "kotake et al. 2007 .", "et al. 2007 . the", "al. 2007 . the expression", "2007 . the expression of", ". the expression of polycomb", "the expression of polycomb constituents", "expression of polycomb constituents of", "of polycomb constituents of prc2", "constituents of prc2 kuzmichev", "of prc2 kuzmichev et", "prc2 kuzmichev et al.", "2002 ezh2", "ezh2 eed and suz12", "and suz12 and", "suz12 and thereby", "and thereby formation of the", "thereby formation of the prc2", "of the prc2 is", "the prc2 is positively", "prc2 is positively regulated", "is positively regulated in growing", "positively regulated in growing cells", "regulated in growing cells by", "in growing cells by e2f1", "cells by e2f1 e2f2", "by e2f1 e2f2 and", "e2f1 e2f2 and e2f3", "e2f2 and e2f3 weinmann", "and e2f3 weinmann et", "e2f3 weinmann et al.", "et al. 2001 bracken", "al. 2001 bracken et", "2001 bracken et al.", "bracken et al. 2003 .", "et al. 2003 . h3k27me3", "al. 2003 . h3k27me3 mark", "2003 . h3k27me3 mark serves", ". h3k27me3 mark serves as", "h3k27me3 mark serves as a", "mark serves as a docking", "serves as a docking site", "as a docking site for", "a docking site for the", "docking site for the polycomb", "site for the polycomb repressor", "for the polycomb repressor complex", "the polycomb repressor complex 1", "repressor complex 1 prc1", "1 prc1 that", "prc1 that contains bmi1", "that contains bmi1 pcgf4", "bmi1 pcgf4 and", "pcgf4 and is therefore", "and is therefore named prc1.4", "therefore named prc1.4 leading", "named prc1.4 leading to", "prc1.4 leading to the", "leading to the repression of", "to the repression of transcription", "the repression of transcription of", "repression of transcription of p16ink4a", "of transcription of p16ink4a and", "transcription of p16ink4a and p14arf", "of p16ink4a and p14arf from", "p16ink4a and p14arf from the", "and p14arf from the cdkn2a", "p14arf from the cdkn2a locus", "the cdkn2a locus where", "cdkn2a locus where pcr1.4", "locus where pcr1.4 mediated", "where pcr1.4 mediated repression of", "pcr1.4 mediated repression of p14arf", "mediated repression of p14arf transcription", "repression of p14arf transcription in", "of p14arf transcription in humans", "p14arf transcription in humans may", "transcription in humans may be", "in humans may be context", "humans may be context dependent", "be context dependent voncken", "context dependent voncken et", "dependent voncken et al.", "et al. 2005 dietrich", "al. 2005 dietrich et", "2005 dietrich et al.", "et al. 2007 agherbi", "al. 2007 agherbi et", "2007 agherbi et al.", "et al. 2009 gao", "al. 2009 gao et", "2009 gao et al.", "gao et al. 2012 .", "et al. 2012 . mapkapk2", "al. 2012 . mapkapk2 and", "2012 . mapkapk2 and mapkapk3", "mapkapk2 and mapkapk3 activated", "and mapkapk3 activated downstream", "mapkapk3 activated downstream of", "activated downstream of the map3k5", "downstream of the map3k5 p38", "of the map3k5 p38 mapk", "the map3k5 p38 mapk cascade", "p38 mapk cascade phosphorylate", "mapk cascade phosphorylate bmi1", "cascade phosphorylate bmi1 of", "phosphorylate bmi1 of the prc1.4", "bmi1 of the prc1.4 complex", "the prc1.4 complex leading", "prc1.4 complex leading to", "complex leading to dissociation", "leading to dissociation of prc1.4", "to dissociation of prc1.4 complex", "dissociation of prc1.4 complex from", "of prc1.4 complex from the", "prc1.4 complex from the cdkn2a", "complex from the cdkn2a locus", "from the cdkn2a locus and", "the cdkn2a locus and upregulation", "cdkn2a locus and upregulation of", "locus and upregulation of p14arf", "and upregulation of p14arf transcription", "of p14arf transcription voncken", "p14arf transcription voncken et", "transcription voncken et al.", "voncken et al. 2005 .", "et al. 2005 . ap", "al. 2005 . ap 1", "2005 . ap 1 transcription", ". ap 1 transcription factor", "1 transcription factor formed", "transcription factor formed as", "factor formed as a", "formed as a result of", "as a result of map3k5", "a result of map3k5 jnk", "result of map3k5 jnk signaling", "map3k5 jnk signaling as", "jnk signaling as well", "signaling as well as", "as well as ras signaling", "as ras signaling binds", "ras signaling binds the", "signaling binds the promoter", "binds the promoter of kdm6b", "promoter of kdm6b jmjd3", "kdm6b jmjd3 gene", "jmjd3 gene and stimulates", "gene and stimulates kdm6b expression.", "and stimulates kdm6b expression. kdm6b", "stimulates kdm6b expression. kdm6b is", "kdm6b expression. kdm6b is a", "expression. kdm6b is a histone", "kdm6b is a histone demethylase", "is a histone demethylase that", "a histone demethylase that removes", "histone demethylase that removes h3k27me3", "demethylase that removes h3k27me3 mark", "that removes h3k27me3 mark i.e.", "removes h3k27me3 mark i.e. demethylates", "h3k27me3 mark i.e. demethylates lysine", "mark i.e. demethylates lysine k28", "i.e. demethylates lysine k28 of", "demethylates lysine k28 of hist1h3a", "k28 of hist1h3a thereby", "of hist1h3a thereby preventing", "hist1h3a thereby preventing prc1.4", "thereby preventing prc1.4 binding to", "preventing prc1.4 binding to the", "prc1.4 binding to the cdkn2a", "binding to the cdkn2a locus", "to the cdkn2a locus and", "the cdkn2a locus and allowing", "cdkn2a locus and allowing transcription", "locus and allowing transcription of", "and allowing transcription of p16ink4a", "transcription of p16ink4a agger", "of p16ink4a agger et", "p16ink4a agger et al.", "et al. 2009 barradas", "al. 2009 barradas et", "2009 barradas et al.", "et al. 2009 lin", "al. 2009 lin et", "2009 lin et al.", "lin et al. 2012 .

", "et al. 2012 .


p16ink4a", "al. 2012 .


p16ink4a inhibits", "2012 .


p16ink4a inhibits phosphorylation", ".


p16ink4a inhibits phosphorylation mediated", "
p16ink4a inhibits phosphorylation mediated inactivation", "inhibits phosphorylation mediated inactivation of", "phosphorylation mediated inactivation of rb", "mediated inactivation of rb family", "inactivation of rb family members", "of rb family members by", "rb family members by cdk4", "family members by cdk4 and", "members by cdk4 and cdk6", "cdk4 and cdk6 leading", "and cdk6 leading to", "cdk6 leading to cell", "leading to cell cycle arrest", "cell cycle arrest serrano", "cycle arrest serrano et", "arrest serrano et al.", "serrano et al. 1993 .", "et al. 1993 . p14arf", "al. 1993 . p14arf inhibits", "1993 . p14arf inhibits mdm2", ". p14arf inhibits mdm2 mediated", "p14arf inhibits mdm2 mediated degradation", "inhibits mdm2 mediated degradation of", "mdm2 mediated degradation of tp53", "degradation of tp53 p53", "p53 zhang et", "al. 1998 which", "1998 which also", "which also contributes to cell", "also contributes to cell cycle", "contributes to cell cycle arrest", "to cell cycle arrest in", "cell cycle arrest in cells", "cycle arrest in cells undergoing", "arrest in cells undergoing oxidative", "in cells undergoing oxidative stress.", "cells undergoing oxidative stress. in", "undergoing oxidative stress. in addition", "stress. in addition phosphorylation", "in addition phosphorylation of", "addition phosphorylation of tp53", "phosphorylation of tp53 by mapkapk5", "tp53 by mapkapk5 prak", "mapkapk5 prak activated", "prak activated downstream of", "activated downstream of map3k5 p38", "downstream of map3k5 p38 mapk", "of map3k5 p38 mapk signaling", "p38 mapk signaling activates", "mapk signaling activates tp53", "signaling activates tp53 and", "activates tp53 and contributes to", "tp53 and contributes to cellular", "and contributes to cellular senescence", "to cellular senescence sun", "cellular senescence sun et", "senescence sun et al.", "sun et al. 2007 ." ] }, { "record_id": "GLY_000594_1_237", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2559582", "r hsa", "hsa 2559582", "r hsa 2559582" ] }, { "record_id": "GLY_000594_1_237", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "senescence associated", "associated secretory", "secretory phenotype", "senescence associated secretory", "associated secretory phenotype", "phenotype sasp", "senescence associated secretory phenotype", "secretory phenotype sasp", "associated secretory phenotype sasp", "the culture", "culture medium", "medium of", "of senescent", "senescent cells", "cells in", "in enriched", "enriched in", "in secreted", "secreted proteins", "proteins when", "when compared", "compared with", "with the", "of quiescent", "quiescent i.e.", "i.e. presenescent", "presenescent cells", "cells and", "and these", "these secreted", "proteins constitute", "constitute the", "the so", "so called", "called senescence", "also known", "known as", "as the", "the senescence", "senescence messaging", "messaging secretome", "sms .", ". sasp", "sasp components", "components include", "include inflammatory", "inflammatory and", "and immune", "immune modulatory", "modulatory cytokines", "e.g. il6", "il6 and", "and il8", "growth factors", "e.g. igfbps", "shed cell", "cell surface", "surface molecules", "e.g. tnf", "tnf receptors", "and survival", "survival factors.", "factors. while", "while the", "the sasp", "sasp exhibits", "exhibits a", "a wide", "wide ranging", "ranging profile", "it is", "is not", "not significantly", "significantly affected", "affected by", "by the", "the type", "type of", "of senescence", "senescence trigger", "oncogenic signalling", "oxidative stress", "stress or", "or dna", "dna damage", "or the", "the cell", "cell type", "epithelial vs.", "vs. mesenchymal", "coppe et", "et al.", "al. 2008", "2008 .", ". however", "as both", "both oxidative", "stress and", "and oncogenic", "oncogenic signaling", "signaling induce", "induce dna", "the persistent", "persistent dna", "damage may", "may be", "be a", "a deciding", "deciding sasp", "sasp initiator", "rodier et", "al. 2009", "2009 .", "components function", "function in", "in an", "an autocrine", "autocrine manner", "reinforcing the", "the senescent", "senescent phenotype", "kuilman et", "acosta et", "and in", "in the", "the paracrine", "paracrine manner", "where they", "they may", "may promote", "promote epithelial", "epithelial to", "to mesenchymal", "mesenchymal transition", "and malignancy", "malignancy in", "the nearby", "nearby premalignant", "premalignant or", "or malignant", "malignant cells", ". interleukin", "interleukin 1", "1 alpha", "a minor", "minor sasp", "sasp component", "component whose", "whose transcription", "transcription is", "is stimulated", "stimulated by", "the ap", "ap 1", "bailly et", "al. 1996", "can cause", "cause paracrine", "paracrine senescence", "senescence through", "through il1", "il1 and", "and inflammasome", "inflammasome signaling", "al. 2013", "2013 .

here", "transcriptional regulatory", "regulatory processes", "processes that", "that mediate", "mediate the", "sasp are", "are annotated.", "annotated. dna", "damage triggers", "triggers atm", "atm mediated", "mediated activation", "activation of", "of tp53", "resulting in", "the increased", "increased level", "level of", "of cdkn1a", "p21 .", ". cdkn1a", "cdkn1a mediated", "mediated inhibition", "inhibition of", "of cdk2", "cdk2 prevents", "prevents phosphorylation", "phosphorylation and", "and inactivation", "inactivation of", "of the", "the cdh1:apc/c", "cdh1:apc/c complex", "allowing it", "it to", "to ubiquitinate", "ubiquitinate and", "and target", "target for", "for degradation", "degradation ehmt1", "ehmt1 and", "and ehmt2", "ehmt2 histone", "histone methyltransferases.", "methyltransferases. as", "as ehmt1", "ehmt2 methylate", "methylate and", "and silence", "silence the", "the promoters", "promoters of", "of il6", "il8 genes", "degradation of", "of these", "these methyltransferases", "methyltransferases relieves", "relieves the", "the inhibition", "il8 transcription", "takahashi et", "al. 2012", "2012 .", ". in", "in addition", "oncogenic ras", "ras signaling", "signaling activates", "activates the", "the cebpb", "c/ebp beta", "transcription factor", "nakajima et", "al. 1993", "lee et", "al. 2010", "which binds", "binds promoters", "genes and", "and stimulates", "stimulates their", "their transcription", "2010 .", ". cebpb", "cebpb also", "also stimulates", "stimulates the", "the transcription", "transcription of", "of cdkn2b", "p15 ink4b", "cell cycle", "cycle arrest", "cebpb transcription", "factor has", "has three", "three isoforms", "due to", "to three", "three alternative", "alternative translation", "translation start", "start sites.", "sites. the", "cebpb 1", "1 isoform", "beta 1", "seems to", "to be", "be exclusively", "exclusively involved", "involved in", "in growth", "growth arrest", "arrest and", "and senescence", "cebpb 2", "beta 2", "isoform may", "promote cellular", "cellular proliferation", "atwood and", "and sealy", "sealy 2010", "2010 and", "and 2011", "2011 .", ". il6", "il6 signaling", "signaling stimulates", "of cebpb", "niehof et", "al. 2001", "creating a", "a positive", "positive feedback", "feedback loop", ". nf", "nf kappa", "kappa b", "b transcription", "factor is", "is also", "also activated", "activated in", "in senescence", "chien et", "al. 2011", "il1 signaling", "jimi et", "hartupee et", "orjalo et", "b binds", "binds il6", "il8 promoters", "promoters and", "and cooperates", "cooperates with", "with cebpb", "factor in", "the induction", "induction of", "matsusaka et", ". besides", "besides il6", "their receptors", "receptors are", "are also", "also upregulated", "upregulated in", "and il6", "il8 may", "be master", "master regulators", "regulators of", "the sasp.

igfbp7", "sasp.

igfbp7 is", "also an", "an sasp", "component that", "that is", "is upregulated", "in response", "response to", "to oncogenic", "ras raf", "raf mapk", "mapk signaling", "signaling and", "and oxidative", "as its", "its transcription", "is directly", "directly stimulated", "transcription factor.", "factor. igfbp7", "igfbp7 negatively", "negatively regulates", "regulates ras", "and is", "is important", "important for", "for the", "the establishment", "establishment of", "senescence in", "in melanocytes", "wajapeyee et", "2008 .

please", ".

please refer", "refer to", "to young", "young and", "and narita", "narita 2009", "2009 for", "for a", "a recent", "recent review.", "the culture medium", "culture medium of", "medium of senescent", "of senescent cells", "senescent cells in", "cells in enriched", "in enriched in", "enriched in secreted", "in secreted proteins", "secreted proteins when", "proteins when compared", "when compared with", "compared with the", "with the culture", "medium of quiescent", "of quiescent i.e.", "quiescent i.e. presenescent", "i.e. presenescent cells", "presenescent cells and", "cells and these", "and these secreted", "these secreted proteins", "secreted proteins constitute", "proteins constitute the", "constitute the so", "the so called", "so called senescence", "called senescence associated", "also known as", "known as the", "as the senescence", "the senescence messaging", "senescence messaging secretome", "secretome sms", "sms . sasp", ". sasp components", "sasp components include", "components include inflammatory", "include inflammatory and", "inflammatory and immune", "and immune modulatory", "immune modulatory cytokines", "cytokines e.g.", "e.g. il6 and", "il6 and il8", "factors e.g.", "shed cell surface", "cell surface molecules", "molecules e.g.", "e.g. tnf receptors", "receptors and", "and survival factors.", "survival factors. while", "factors. while the", "while the sasp", "the sasp exhibits", "sasp exhibits a", "exhibits a wide", "a wide ranging", "wide ranging profile", "profile it", "it is not", "is not significantly", "not significantly affected", "significantly affected by", "affected by the", "by the type", "the type of", "type of senescence", "of senescence trigger", "trigger oncogenic", "signalling oxidative", "oxidative stress or", "stress or dna", "or dna damage", "damage or", "or the cell", "the cell type", "type epithelial", "epithelial vs. mesenchymal", "coppe et al.", "et al. 2008", "al. 2008 .", "2008 . however", "however as", "as both oxidative", "both oxidative stress", "oxidative stress and", "stress and oncogenic", "and oncogenic signaling", "oncogenic signaling induce", "signaling induce dna", "induce dna damage", "damage the", "the persistent dna", "persistent dna damage", "dna damage may", "damage may be", "may be a", "be a deciding", "a deciding sasp", "deciding sasp initiator", "initiator rodier", "rodier et al.", "et al. 2009", "al. 2009 .", "2009 . sasp", "sasp components function", "components function in", "function in an", "in an autocrine", "an autocrine manner", "manner reinforcing", "reinforcing the senescent", "the senescent phenotype", "phenotype kuilman", "kuilman et al.", "2008 acosta", "acosta et al.", "and in the", "in the paracrine", "the paracrine manner", "manner where", "where they may", "they may promote", "may promote epithelial", "promote epithelial to", "epithelial to mesenchymal", "to mesenchymal transition", "transition emt", "emt and", "and malignancy in", "malignancy in the", "in the nearby", "the nearby premalignant", "nearby premalignant or", "premalignant or malignant", "or malignant cells", "cells coppe", "2008 . interleukin", ". interleukin 1", "interleukin 1 alpha", "alpha il1a", "a minor sasp", "minor sasp component", "sasp component whose", "component whose transcription", "whose transcription is", "transcription is stimulated", "is stimulated by", "stimulated by the", "by the ap", "the ap 1", "1 fos:jun", "fos:jun complex", "complex bailly", "bailly et al.", "et al. 1996", "can cause paracrine", "cause paracrine senescence", "paracrine senescence through", "senescence through il1", "through il1 and", "il1 and inflammasome", "and inflammasome signaling", "signaling acosta", "et al. 2013", "al. 2013 .

here", ".

here transcriptional", "transcriptional regulatory processes", "regulatory processes that", "processes that mediate", "that mediate the", "mediate the sasp", "the sasp are", "sasp are annotated.", "are annotated. dna", "annotated. dna damage", "dna damage triggers", "damage triggers atm", "triggers atm mediated", "atm mediated activation", "mediated activation of", "activation of tp53", "tp53 resulting", "resulting in the", "in the increased", "the increased level", "increased level of", "level of cdkn1a", "cdkn1a p21", "p21 . cdkn1a", ". cdkn1a mediated", "cdkn1a mediated inhibition", "mediated inhibition of", "inhibition of cdk2", "of cdk2 prevents", "cdk2 prevents phosphorylation", "prevents phosphorylation and", "phosphorylation and inactivation", "and inactivation of", "inactivation of the", "of the cdh1:apc/c", "the cdh1:apc/c complex", "complex allowing", "allowing it to", "it to ubiquitinate", "to ubiquitinate and", "ubiquitinate and target", "and target for", "target for degradation", "for degradation ehmt1", "degradation ehmt1 and", "ehmt1 and ehmt2", "and ehmt2 histone", "ehmt2 histone methyltransferases.", "histone methyltransferases. as", "methyltransferases. as ehmt1", "as ehmt1 and", "and ehmt2 methylate", "ehmt2 methylate and", "methylate and silence", "and silence the", "silence the promoters", "the promoters of", "promoters of il6", "of il6 and", "and il8 genes", "genes degradation", "degradation of these", "of these methyltransferases", "these methyltransferases relieves", "methyltransferases relieves the", "relieves the inhibition", "the inhibition of", "inhibition of il6", "and il8 transcription", "transcription takahashi", "takahashi et al.", "et al. 2012", "al. 2012 .", "2012 . in", ". in addition", "addition oncogenic", "oncogenic ras signaling", "ras signaling activates", "signaling activates the", "activates the cebpb", "cebpb c/ebp", "beta transcription", "factor nakajima", "nakajima et al.", "et al. 1993", "1993 lee", "lee et al.", "et al. 2010", "which binds promoters", "binds promoters of", "il8 genes and", "genes and stimulates", "and stimulates their", "stimulates their transcription", "transcription kuilman", "2008 lee", "al. 2010 .", "2010 . cebpb", ". cebpb also", "cebpb also stimulates", "also stimulates the", "stimulates the transcription", "the transcription of", "transcription of cdkn2b", "cdkn2b p15", "reinforcing the cell", "the cell cycle", "cell cycle arrest", "arrest kuilman", "2008 . cebpb", ". cebpb transcription", "cebpb transcription factor", "transcription factor has", "factor has three", "has three isoforms", "isoforms due", "due to three", "to three alternative", "three alternative translation", "alternative translation start", "translation start sites.", "start sites. the", "sites. the cebpb", "the cebpb 1", "cebpb 1 isoform", "isoform c/ebp", "c/ebp beta 1", "1 seems", "seems to be", "to be exclusively", "be exclusively involved", "exclusively involved in", "involved in growth", "in growth arrest", "growth arrest and", "arrest and senescence", "senescence while", "while the cebpb", "the cebpb 2", "2 c/ebp", "c/ebp beta 2", "2 isoform", "isoform may promote", "may promote cellular", "promote cellular proliferation", "proliferation atwood", "atwood and sealy", "and sealy 2010", "sealy 2010 and", "2010 and 2011", "and 2011 .", "2011 . il6", ". il6 signaling", "il6 signaling stimulates", "signaling stimulates the", "transcription of cebpb", "cebpb niehof", "niehof et al.", "et al. 2001", "creating a positive", "a positive feedback", "positive feedback loop", "loop kuilman", "2009 lee", "2010 . nf", ". nf kappa", "nf kappa b", "kappa b transcription", "b transcription factor", "transcription factor is", "factor is also", "is also activated", "also activated in", "activated in senescence", "senescence chien", "chien et al.", "et al. 2011", "2011 through", "through il1 signaling", "signaling jimi", "jimi et al.", "1996 hartupee", "hartupee et al.", "2008 orjalo", "orjalo et al.", "2009 . nf", "kappa b binds", "b binds il6", "binds il6 and", "and il8 promoters", "il8 promoters and", "promoters and cooperates", "and cooperates with", "cooperates with cebpb", "with cebpb transcription", "transcription factor in", "factor in the", "in the induction", "the induction of", "induction of il6", "transcription matsusaka", "matsusaka et al.", "1993 acosta", "2008 . besides", ". besides il6", "besides il6 and", "il8 their", "their receptors are", "receptors are also", "are also upregulated", "also upregulated in", "upregulated in senescence", "senescence kuilman", "2008 and", "and il6 and", "and il8 may", "il8 may be", "may be master", "be master regulators", "master regulators of", "regulators of the", "of the sasp.

igfbp7", "the sasp.

igfbp7 is", "sasp.

igfbp7 is also", "is also an", "also an sasp", "an sasp component", "sasp component that", "component that is", "that is upregulated", "is upregulated in", "upregulated in response", "in response to", "response to oncogenic", "to oncogenic ras", "oncogenic ras raf", "ras raf mapk", "raf mapk signaling", "mapk signaling and", "signaling and oxidative", "and oxidative stress", "stress as", "as its transcription", "its transcription is", "transcription is directly", "is directly stimulated", "directly stimulated by", "1 jun:fos", "jun:fos transcription", "transcription factor. igfbp7", "factor. igfbp7 negatively", "igfbp7 negatively regulates", "negatively regulates ras", "regulates ras raf", "raf braf", "braf mapk", "signaling and is", "and is important", "is important for", "important for the", "for the establishment", "the establishment of", "establishment of senescence", "of senescence in", "senescence in melanocytes", "melanocytes wajapeyee", "wajapeyee et al.", "al. 2008 .

please", "2008 .

please refer", ".

please refer to", "refer to young", "to young and", "young and narita", "and narita 2009", "narita 2009 for", "2009 for a", "for a recent", "a recent review.", "the culture medium of", "culture medium of senescent", "medium of senescent cells", "of senescent cells in", "senescent cells in enriched", "cells in enriched in", "in enriched in secreted", "enriched in secreted proteins", "in secreted proteins when", "secreted proteins when compared", "proteins when compared with", "when compared with the", "compared with the culture", "with the culture medium", "culture medium of quiescent", "medium of quiescent i.e.", "of quiescent i.e. presenescent", "quiescent i.e. presenescent cells", "i.e. presenescent cells and", "presenescent cells and these", "cells and these secreted", "and these secreted proteins", "these secreted proteins constitute", "secreted proteins constitute the", "proteins constitute the so", "constitute the so called", "the so called senescence", "so called senescence associated", "called senescence associated secretory", "sasp also", "also known as the", "known as the senescence", "as the senescence messaging", "the senescence messaging secretome", "messaging secretome sms", "secretome sms .", "sms . sasp components", ". sasp components include", "sasp components include inflammatory", "components include inflammatory and", "include inflammatory and immune", "inflammatory and immune modulatory", "and immune modulatory cytokines", "modulatory cytokines e.g.", "cytokines e.g. il6", "e.g. il6 and il8", "il8 growth", "growth factors e.g.", "factors e.g. igfbps", "igfbps shed", "shed cell surface molecules", "surface molecules e.g.", "molecules e.g. tnf", "tnf receptors and", "receptors and survival", "and survival factors. while", "survival factors. while the", "factors. while the sasp", "while the sasp exhibits", "the sasp exhibits a", "sasp exhibits a wide", "exhibits a wide ranging", "a wide ranging profile", "ranging profile it", "profile it is", "it is not significantly", "is not significantly affected", "not significantly affected by", "significantly affected by the", "affected by the type", "by the type of", "the type of senescence", "type of senescence trigger", "senescence trigger oncogenic", "trigger oncogenic signalling", "oncogenic signalling oxidative", "signalling oxidative stress", "oxidative stress or dna", "stress or dna damage", "dna damage or", "damage or the", "or the cell type", "cell type epithelial", "type epithelial vs.", "mesenchymal coppe", "coppe et al. 2008", "et al. 2008 .", "al. 2008 . however", ". however as", "however as both", "as both oxidative stress", "both oxidative stress and", "oxidative stress and oncogenic", "stress and oncogenic signaling", "and oncogenic signaling induce", "oncogenic signaling induce dna", "signaling induce dna damage", "dna damage the", "damage the persistent", "the persistent dna damage", "persistent dna damage may", "dna damage may be", "damage may be a", "may be a deciding", "be a deciding sasp", "a deciding sasp initiator", "sasp initiator rodier", "initiator rodier et", "rodier et al. 2009", "et al. 2009 .", "al. 2009 . sasp", "2009 . sasp components", ". sasp components function", "sasp components function in", "components function in an", "function in an autocrine", "in an autocrine manner", "autocrine manner reinforcing", "manner reinforcing the", "reinforcing the senescent phenotype", "senescent phenotype kuilman", "phenotype kuilman et", "kuilman et al. 2008", "al. 2008 acosta", "2008 acosta et", "acosta et al. 2008", "and in the paracrine", "in the paracrine manner", "paracrine manner where", "manner where they", "where they may promote", "they may promote epithelial", "may promote epithelial to", "promote epithelial to mesenchymal", "epithelial to mesenchymal transition", "mesenchymal transition emt", "emt and malignancy", "and malignancy in the", "malignancy in the nearby", "in the nearby premalignant", "the nearby premalignant or", "nearby premalignant or malignant", "premalignant or malignant cells", "malignant cells coppe", "cells coppe et", "al. 2008 . interleukin", "2008 . interleukin 1", ". interleukin 1 alpha", "1 alpha il1a", "il1a a", "a minor sasp component", "minor sasp component whose", "sasp component whose transcription", "component whose transcription is", "whose transcription is stimulated", "transcription is stimulated by", "is stimulated by the", "stimulated by the ap", "by the ap 1", "ap 1 fos:jun", "complex bailly et", "bailly et al. 1996", "1996 can", "can cause paracrine senescence", "cause paracrine senescence through", "paracrine senescence through il1", "senescence through il1 and", "through il1 and inflammasome", "il1 and inflammasome signaling", "inflammasome signaling acosta", "signaling acosta et", "acosta et al. 2013", "et al. 2013 .

here", "2013 .

here transcriptional", ".

here transcriptional regulatory", "transcriptional regulatory processes that", "regulatory processes that mediate", "processes that mediate the", "that mediate the sasp", "mediate the sasp are", "the sasp are annotated.", "sasp are annotated. dna", "are annotated. dna damage", "annotated. dna damage triggers", "dna damage triggers atm", "damage triggers atm mediated", "triggers atm mediated activation", "atm mediated activation of", "mediated activation of tp53", "of tp53 resulting", "tp53 resulting in", "resulting in the increased", "in the increased level", "the increased level of", "increased level of cdkn1a", "of cdkn1a p21", "cdkn1a p21 .", "p21 . cdkn1a mediated", ". cdkn1a mediated inhibition", "cdkn1a mediated inhibition of", "mediated inhibition of cdk2", "inhibition of cdk2 prevents", "of cdk2 prevents phosphorylation", "cdk2 prevents phosphorylation and", "prevents phosphorylation and inactivation", "phosphorylation and inactivation of", "and inactivation of the", "inactivation of the cdh1:apc/c", "of the cdh1:apc/c complex", "cdh1:apc/c complex allowing", "complex allowing it", "allowing it to ubiquitinate", "it to ubiquitinate and", "to ubiquitinate and target", "ubiquitinate and target for", "and target for degradation", "target for degradation ehmt1", "for degradation ehmt1 and", "degradation ehmt1 and ehmt2", "ehmt1 and ehmt2 histone", "and ehmt2 histone methyltransferases.", "ehmt2 histone methyltransferases. as", "histone methyltransferases. as ehmt1", "methyltransferases. as ehmt1 and", "as ehmt1 and ehmt2", "ehmt1 and ehmt2 methylate", "and ehmt2 methylate and", "ehmt2 methylate and silence", "methylate and silence the", "and silence the promoters", "silence the promoters of", "the promoters of il6", "promoters of il6 and", "of il6 and il8", "il6 and il8 genes", "il8 genes degradation", "genes degradation of", "degradation of these methyltransferases", "of these methyltransferases relieves", "these methyltransferases relieves the", "methyltransferases relieves the inhibition", "relieves the inhibition of", "the inhibition of il6", "inhibition of il6 and", "il6 and il8 transcription", "il8 transcription takahashi", "transcription takahashi et", "takahashi et al. 2012", "et al. 2012 .", "al. 2012 . in", "2012 . in addition", "in addition oncogenic", "addition oncogenic ras", "oncogenic ras signaling activates", "ras signaling activates the", "signaling activates the cebpb", "the cebpb c/ebp", "cebpb c/ebp beta", "c/ebp beta transcription", "beta transcription factor", "transcription factor nakajima", "factor nakajima et", "nakajima et al. 1993", "al. 1993 lee", "1993 lee et", "lee et al. 2010", "2010 which", "which binds promoters of", "binds promoters of il6", "and il8 genes and", "il8 genes and stimulates", "genes and stimulates their", "and stimulates their transcription", "their transcription kuilman", "transcription kuilman et", "al. 2008 lee", "2008 lee et", "et al. 2010 .", "al. 2010 . cebpb", "2010 . cebpb also", ". cebpb also stimulates", "cebpb also stimulates the", "also stimulates the transcription", "stimulates the transcription of", "the transcription of cdkn2b", "of cdkn2b p15", "cdkn2b p15 ink4b", "ink4b reinforcing", "reinforcing the cell cycle", "the cell cycle arrest", "cycle arrest kuilman", "arrest kuilman et", "al. 2008 . cebpb", "2008 . cebpb transcription", ". cebpb transcription factor", "cebpb transcription factor has", "transcription factor has three", "factor has three isoforms", "three isoforms due", "isoforms due to", "due to three alternative", "to three alternative translation", "three alternative translation start", "alternative translation start sites.", "translation start sites. the", "start sites. the cebpb", "sites. the cebpb 1", "the cebpb 1 isoform", "1 isoform c/ebp", "isoform c/ebp beta", "beta 1 seems", "1 seems to", "seems to be exclusively", "to be exclusively involved", "be exclusively involved in", "exclusively involved in growth", "involved in growth arrest", "in growth arrest and", "growth arrest and senescence", "and senescence while", "senescence while the", "while the cebpb 2", "cebpb 2 c/ebp", "2 c/ebp beta", "beta 2 isoform", "2 isoform may", "isoform may promote cellular", "may promote cellular proliferation", "cellular proliferation atwood", "proliferation atwood and", "atwood and sealy 2010", "and sealy 2010 and", "sealy 2010 and 2011", "2010 and 2011 .", "and 2011 . il6", "2011 . il6 signaling", ". il6 signaling stimulates", "il6 signaling stimulates the", "signaling stimulates the transcription", "the transcription of cebpb", "of cebpb niehof", "cebpb niehof et", "niehof et al. 2001", "2001 creating", "creating a positive feedback", "a positive feedback loop", "feedback loop kuilman", "loop kuilman et", "kuilman et al. 2009", "al. 2009 lee", "2009 lee et", "al. 2010 . nf", "2010 . nf kappa", ". nf kappa b", "nf kappa b transcription", "kappa b transcription factor", "b transcription factor is", "transcription factor is also", "factor is also activated", "is also activated in", "also activated in senescence", "in senescence chien", "senescence chien et", "chien et al. 2011", "al. 2011 through", "2011 through il1", "il1 signaling jimi", "signaling jimi et", "jimi et al. 1996", "al. 1996 hartupee", "1996 hartupee et", "hartupee et al. 2008", "al. 2008 orjalo", "2008 orjalo et", "orjalo et al. 2009", "al. 2009 . nf", "2009 . nf kappa", "nf kappa b binds", "kappa b binds il6", "b binds il6 and", "binds il6 and il8", "il6 and il8 promoters", "and il8 promoters and", "il8 promoters and cooperates", "promoters and cooperates with", "and cooperates with cebpb", "cooperates with cebpb transcription", "with cebpb transcription factor", "cebpb transcription factor in", "transcription factor in the", "factor in the induction", "in the induction of", "the induction of il6", "induction of il6 and", "il8 transcription matsusaka", "transcription matsusaka et", "matsusaka et al. 1993", "al. 1993 acosta", "1993 acosta et", "al. 2008 . besides", "2008 . besides il6", ". besides il6 and", "besides il6 and il8", "and il8 their", "il8 their receptors", "their receptors are also", "receptors are also upregulated", "are also upregulated in", "also upregulated in senescence", "in senescence kuilman", "senescence kuilman et", "al. 2008 and", "2008 and il6", "and il6 and il8", "il6 and il8 may", "and il8 may be", "il8 may be master", "may be master regulators", "be master regulators of", "master regulators of the", "regulators of the sasp.

igfbp7", "of the sasp.

igfbp7 is", "the sasp.

igfbp7 is also", "sasp.

igfbp7 is also an", "is also an sasp", "also an sasp component", "an sasp component that", "sasp component that is", "component that is upregulated", "that is upregulated in", "is upregulated in response", "upregulated in response to", "in response to oncogenic", "response to oncogenic ras", "to oncogenic ras raf", "oncogenic ras raf mapk", "ras raf mapk signaling", "raf mapk signaling and", "mapk signaling and oxidative", "signaling and oxidative stress", "oxidative stress as", "stress as its", "as its transcription is", "its transcription is directly", "transcription is directly stimulated", "is directly stimulated by", "directly stimulated by the", "ap 1 jun:fos", "jun:fos transcription factor.", "transcription factor. igfbp7 negatively", "factor. igfbp7 negatively regulates", "igfbp7 negatively regulates ras", "negatively regulates ras raf", "ras raf braf", "braf mapk signaling", "mapk signaling and is", "signaling and is important", "and is important for", "is important for the", "important for the establishment", "for the establishment of", "the establishment of senescence", "establishment of senescence in", "of senescence in melanocytes", "in melanocytes wajapeyee", "melanocytes wajapeyee et", "wajapeyee et al. 2008", "et al. 2008 .

please", "al. 2008 .

please refer", "2008 .

please refer to", ".

please refer to young", "refer to young and", "to young and narita", "young and narita 2009", "and narita 2009 for", "narita 2009 for a", "2009 for a recent", "for a recent review.", "the culture medium of senescent", "culture medium of senescent cells", "medium of senescent cells in", "of senescent cells in enriched", "senescent cells in enriched in", "cells in enriched in secreted", "in enriched in secreted proteins", "enriched in secreted proteins when", "in secreted proteins when compared", "secreted proteins when compared with", "proteins when compared with the", "when compared with the culture", "compared with the culture medium", "with the culture medium of", "the culture medium of quiescent", "culture medium of quiescent i.e.", "medium of quiescent i.e. presenescent", "of quiescent i.e. presenescent cells", "quiescent i.e. presenescent cells and", "i.e. presenescent cells and these", "presenescent cells and these secreted", "cells and these secreted proteins", "and these secreted proteins constitute", "these secreted proteins constitute the", "secreted proteins constitute the so", "proteins constitute the so called", "constitute the so called senescence", "the so called senescence associated", "so called senescence associated secretory", "called senescence associated secretory phenotype", "sasp also known", "also known as the senescence", "known as the senescence messaging", "as the senescence messaging secretome", "senescence messaging secretome sms", "messaging secretome sms .", "secretome sms . sasp", "sms . sasp components include", ". sasp components include inflammatory", "sasp components include inflammatory and", "components include inflammatory and immune", "include inflammatory and immune modulatory", "inflammatory and immune modulatory cytokines", "immune modulatory cytokines e.g.", "modulatory cytokines e.g. il6", "cytokines e.g. il6 and", "and il8 growth", "il8 growth factors", "growth factors e.g. igfbps", "e.g. igfbps shed", "igfbps shed cell", "cell surface molecules e.g.", "surface molecules e.g. tnf", "molecules e.g. tnf receptors", "e.g. tnf receptors and", "tnf receptors and survival", "receptors and survival factors.", "and survival factors. while the", "survival factors. while the sasp", "factors. while the sasp exhibits", "while the sasp exhibits a", "the sasp exhibits a wide", "sasp exhibits a wide ranging", "exhibits a wide ranging profile", "wide ranging profile it", "ranging profile it is", "profile it is not", "it is not significantly affected", "is not significantly affected by", "not significantly affected by the", "significantly affected by the type", "affected by the type of", "by the type of senescence", "the type of senescence trigger", "of senescence trigger oncogenic", "senescence trigger oncogenic signalling", "oncogenic signalling oxidative stress", "signalling oxidative stress or", "oxidative stress or dna damage", "or dna damage or", "dna damage or the", "damage or the cell", "the cell type epithelial", "cell type epithelial vs.", "type epithelial vs. mesenchymal", "vs. mesenchymal coppe", "mesenchymal coppe et", "coppe et al. 2008 .", "et al. 2008 . however", "2008 . however as", ". however as both", "however as both oxidative", "as both oxidative stress and", "both oxidative stress and oncogenic", "oxidative stress and oncogenic signaling", "stress and oncogenic signaling induce", "and oncogenic signaling induce dna", "oncogenic signaling induce dna damage", "induce dna damage the", "dna damage the persistent", "damage the persistent dna", "the persistent dna damage may", "persistent dna damage may be", "dna damage may be a", "damage may be a deciding", "may be a deciding sasp", "be a deciding sasp initiator", "deciding sasp initiator rodier", "sasp initiator rodier et", "initiator rodier et al.", "rodier et al. 2009 .", "et al. 2009 . sasp", "al. 2009 . sasp components", "2009 . sasp components function", ". sasp components function in", "sasp components function in an", "components function in an autocrine", "function in an autocrine manner", "an autocrine manner reinforcing", "autocrine manner reinforcing the", "manner reinforcing the senescent", "the senescent phenotype kuilman", "senescent phenotype kuilman et", "phenotype kuilman et al.", "et al. 2008 acosta", "al. 2008 acosta et", "2008 acosta et al.", "2008 and in", "and in the paracrine manner", "the paracrine manner where", "paracrine manner where they", "manner where they may", "where they may promote epithelial", "they may promote epithelial to", "may promote epithelial to mesenchymal", "promote epithelial to mesenchymal transition", "to mesenchymal transition emt", "transition emt and", "emt and malignancy in", "and malignancy in the nearby", "malignancy in the nearby premalignant", "in the nearby premalignant or", "the nearby premalignant or malignant", "nearby premalignant or malignant cells", "or malignant cells coppe", "malignant cells coppe et", "cells coppe et al.", "et al. 2008 . interleukin", "al. 2008 . interleukin 1", "2008 . interleukin 1 alpha", "interleukin 1 alpha il1a", "il1a a minor", "a minor sasp component whose", "minor sasp component whose transcription", "sasp component whose transcription is", "component whose transcription is stimulated", "whose transcription is stimulated by", "transcription is stimulated by the", "is stimulated by the ap", "stimulated by the ap 1", "the ap 1 fos:jun", "1 fos:jun complex", "fos:jun complex bailly", "complex bailly et al.", "al. 1996 can", "1996 can cause", "can cause paracrine senescence through", "cause paracrine senescence through il1", "paracrine senescence through il1 and", "senescence through il1 and inflammasome", "through il1 and inflammasome signaling", "and inflammasome signaling acosta", "inflammasome signaling acosta et", "signaling acosta et al.", "acosta et al. 2013 .

here", "al. 2013 .

here transcriptional", "2013 .

here transcriptional regulatory", ".

here transcriptional regulatory processes", "transcriptional regulatory processes that mediate", "regulatory processes that mediate the", "processes that mediate the sasp", "that mediate the sasp are", "mediate the sasp are annotated.", "the sasp are annotated. dna", "sasp are annotated. dna damage", "are annotated. dna damage triggers", "annotated. dna damage triggers atm", "dna damage triggers atm mediated", "damage triggers atm mediated activation", "triggers atm mediated activation of", "atm mediated activation of tp53", "activation of tp53 resulting", "of tp53 resulting in", "tp53 resulting in the", "resulting in the increased level", "in the increased level of", "the increased level of cdkn1a", "level of cdkn1a p21", "of cdkn1a p21 .", "cdkn1a p21 . cdkn1a", "p21 . cdkn1a mediated inhibition", ". cdkn1a mediated inhibition of", "cdkn1a mediated inhibition of cdk2", "mediated inhibition of cdk2 prevents", "inhibition of cdk2 prevents phosphorylation", "of cdk2 prevents phosphorylation and", "cdk2 prevents phosphorylation and inactivation", "prevents phosphorylation and inactivation of", "phosphorylation and inactivation of the", "and inactivation of the cdh1:apc/c", "inactivation of the cdh1:apc/c complex", "the cdh1:apc/c complex allowing", "cdh1:apc/c complex allowing it", "complex allowing it to", "allowing it to ubiquitinate and", "it to ubiquitinate and target", "to ubiquitinate and target for", "ubiquitinate and target for degradation", "and target for degradation ehmt1", "target for degradation ehmt1 and", "for degradation ehmt1 and ehmt2", "degradation ehmt1 and ehmt2 histone", "ehmt1 and ehmt2 histone methyltransferases.", "and ehmt2 histone methyltransferases. as", "ehmt2 histone methyltransferases. as ehmt1", "histone methyltransferases. as ehmt1 and", "methyltransferases. as ehmt1 and ehmt2", "as ehmt1 and ehmt2 methylate", "ehmt1 and ehmt2 methylate and", "and ehmt2 methylate and silence", "ehmt2 methylate and silence the", "methylate and silence the promoters", "and silence the promoters of", "silence the promoters of il6", "the promoters of il6 and", "promoters of il6 and il8", "of il6 and il8 genes", "and il8 genes degradation", "il8 genes degradation of", "genes degradation of these", "degradation of these methyltransferases relieves", "of these methyltransferases relieves the", "these methyltransferases relieves the inhibition", "methyltransferases relieves the inhibition of", "relieves the inhibition of il6", "the inhibition of il6 and", "inhibition of il6 and il8", "of il6 and il8 transcription", "and il8 transcription takahashi", "il8 transcription takahashi et", "transcription takahashi et al.", "takahashi et al. 2012 .", "et al. 2012 . in", "al. 2012 . in addition", ". in addition oncogenic", "in addition oncogenic ras", "addition oncogenic ras signaling", "oncogenic ras signaling activates the", "ras signaling activates the cebpb", "activates the cebpb c/ebp", "the cebpb c/ebp beta", "c/ebp beta transcription factor", "transcription factor nakajima et", "factor nakajima et al.", "et al. 1993 lee", "al. 1993 lee et", "1993 lee et al.", "al. 2010 which", "2010 which binds", "which binds promoters of il6", "binds promoters of il6 and", "il6 and il8 genes and", "and il8 genes and stimulates", "il8 genes and stimulates their", "genes and stimulates their transcription", "stimulates their transcription kuilman", "their transcription kuilman et", "transcription kuilman et al.", "et al. 2008 lee", "al. 2008 lee et", "2008 lee et al.", "lee et al. 2010 .", "et al. 2010 . cebpb", "al. 2010 . cebpb also", "2010 . cebpb also stimulates", ". cebpb also stimulates the", "cebpb also stimulates the transcription", "also stimulates the transcription of", "stimulates the transcription of cdkn2b", "transcription of cdkn2b p15", "of cdkn2b p15 ink4b", "p15 ink4b reinforcing", "ink4b reinforcing the", "reinforcing the cell cycle arrest", "cell cycle arrest kuilman", "cycle arrest kuilman et", "arrest kuilman et al.", "kuilman et al. 2008 .", "et al. 2008 . cebpb", "al. 2008 . cebpb transcription", "2008 . cebpb transcription factor", ". cebpb transcription factor has", "cebpb transcription factor has three", "transcription factor has three isoforms", "has three isoforms due", "three isoforms due to", "isoforms due to three", "due to three alternative translation", "to three alternative translation start", "three alternative translation start sites.", "alternative translation start sites. the", "translation start sites. the cebpb", "start sites. the cebpb 1", "sites. the cebpb 1 isoform", "cebpb 1 isoform c/ebp", "1 isoform c/ebp beta", "isoform c/ebp beta 1", "c/ebp beta 1 seems", "beta 1 seems to", "1 seems to be", "seems to be exclusively involved", "to be exclusively involved in", "be exclusively involved in growth", "exclusively involved in growth arrest", "involved in growth arrest and", "in growth arrest and senescence", "arrest and senescence while", "and senescence while the", "senescence while the cebpb", "the cebpb 2 c/ebp", "cebpb 2 c/ebp beta", "2 c/ebp beta 2", "c/ebp beta 2 isoform", "beta 2 isoform may", "2 isoform may promote", "isoform may promote cellular proliferation", "promote cellular proliferation atwood", "cellular proliferation atwood and", "proliferation atwood and sealy", "atwood and sealy 2010 and", "and sealy 2010 and 2011", "sealy 2010 and 2011 .", "2010 and 2011 . il6", "and 2011 . il6 signaling", "2011 . il6 signaling stimulates", ". il6 signaling stimulates the", "il6 signaling stimulates the transcription", "signaling stimulates the transcription of", "stimulates the transcription of cebpb", "transcription of cebpb niehof", "of cebpb niehof et", "cebpb niehof et al.", "al. 2001 creating", "2001 creating a", "creating a positive feedback loop", "positive feedback loop kuilman", "feedback loop kuilman et", "loop kuilman et al.", "et al. 2009 lee", "al. 2009 lee et", "2009 lee et al.", "et al. 2010 . nf", "al. 2010 . nf kappa", "2010 . nf kappa b", ". nf kappa b transcription", "nf kappa b transcription factor", "kappa b transcription factor is", "b transcription factor is also", "transcription factor is also activated", "factor is also activated in", "is also activated in senescence", "activated in senescence chien", "in senescence chien et", "senescence chien et al.", "et al. 2011 through", "al. 2011 through il1", "2011 through il1 signaling", "through il1 signaling jimi", "il1 signaling jimi et", "signaling jimi et al.", "et al. 1996 hartupee", "al. 1996 hartupee et", "1996 hartupee et al.", "et al. 2008 orjalo", "al. 2008 orjalo et", "2008 orjalo et al.", "orjalo et al. 2009 .", "et al. 2009 . nf", "al. 2009 . nf kappa", "2009 . nf kappa b", ". nf kappa b binds", "nf kappa b binds il6", "kappa b binds il6 and", "b binds il6 and il8", "binds il6 and il8 promoters", "il6 and il8 promoters and", "and il8 promoters and cooperates", "il8 promoters and cooperates with", "promoters and cooperates with cebpb", "and cooperates with cebpb transcription", "cooperates with cebpb transcription factor", "with cebpb transcription factor in", "cebpb transcription factor in the", "transcription factor in the induction", "factor in the induction of", "in the induction of il6", "the induction of il6 and", "induction of il6 and il8", "and il8 transcription matsusaka", "il8 transcription matsusaka et", "transcription matsusaka et al.", "et al. 1993 acosta", "al. 1993 acosta et", "1993 acosta et al.", "acosta et al. 2008 .", "et al. 2008 . besides", "al. 2008 . besides il6", "2008 . besides il6 and", ". besides il6 and il8", "il6 and il8 their", "and il8 their receptors", "il8 their receptors are", "their receptors are also upregulated", "receptors are also upregulated in", "are also upregulated in senescence", "upregulated in senescence kuilman", "in senescence kuilman et", "senescence kuilman et al.", "et al. 2008 and", "al. 2008 and il6", "2008 and il6 and", "and il6 and il8 may", "il6 and il8 may be", "and il8 may be master", "il8 may be master regulators", "may be master regulators of", "be master regulators of the", "master regulators of the sasp.

igfbp7", "regulators of the sasp.

igfbp7 is", "of the sasp.

igfbp7 is also", "the sasp.

igfbp7 is also an", "sasp.

igfbp7 is also an sasp", "is also an sasp component", "also an sasp component that", "an sasp component that is", "sasp component that is upregulated", "component that is upregulated in", "that is upregulated in response", "is upregulated in response to", "upregulated in response to oncogenic", "in response to oncogenic ras", "response to oncogenic ras raf", "to oncogenic ras raf mapk", "oncogenic ras raf mapk signaling", "ras raf mapk signaling and", "raf mapk signaling and oxidative", "mapk signaling and oxidative stress", "and oxidative stress as", "oxidative stress as its", "stress as its transcription", "as its transcription is directly", "its transcription is directly stimulated", "transcription is directly stimulated by", "is directly stimulated by the", "directly stimulated by the ap", "the ap 1 jun:fos", "1 jun:fos transcription", "jun:fos transcription factor. igfbp7", "transcription factor. igfbp7 negatively regulates", "factor. igfbp7 negatively regulates ras", "igfbp7 negatively regulates ras raf", "regulates ras raf braf", "raf braf mapk", "braf mapk signaling and", "mapk signaling and is important", "signaling and is important for", "and is important for the", "is important for the establishment", "important for the establishment of", "for the establishment of senescence", "the establishment of senescence in", "establishment of senescence in melanocytes", "senescence in melanocytes wajapeyee", "in melanocytes wajapeyee et", "melanocytes wajapeyee et al.", "wajapeyee et al. 2008 .

please", "et al. 2008 .

please refer", "al. 2008 .

please refer to", "2008 .

please refer to young", ".

please refer to young and", "refer to young and narita", "to young and narita 2009", "young and narita 2009 for", "and narita 2009 for a", "narita 2009 for a recent", "2009 for a recent review." ] }, { "record_id": "GLY_000594_1_238", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2559585", "r hsa", "hsa 2559585", "r hsa 2559585" ] }, { "record_id": "GLY_000594_1_238", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "oncogene induced", "induced senescence", "oncogene induced senescence", "is triggered", "triggered by", "by high", "high level", "level of", "of ras/raf/mapk", "ras/raf/mapk signaling", "signaling that", "that can", "can be", "be caused", "for example", "by oncogenic", "oncogenic mutations", "mutations in", "in ras", "ras or", "or raf", "raf proteins", "or by", "in growth", "growth factor", "factor receptors", "such as", "as egfr", "that act", "act upstream", "upstream of", "ras/raf/mapk cascade.", "cascade. oncogene", "senescence can", "can also", "also be", "be triggered", "high transcriptional", "transcriptional activity", "activity of", "of e2f1", "e2f2 or", "or e2f3", "e2f3 which", "which can", "by the", "the loss", "loss of", "of function", "function of", "of rb1", "rb1 tumor", "tumor suppressor.

oncogenic", "suppressor.

oncogenic signals", "signals trigger", "trigger transcription", "transcription of", "of cdkn2a", "cdkn2a locus", "locus tumor", "tumor suppressor", "suppressor genes:", "genes: p16ink4a", "p16ink4a and", "and p14arf.", "p14arf. p16ink4a", "and p14arf", "p14arf share", "share exons", "exons 2", "2 and", "and 3", "but are", "are expressed", "expressed from", "from different", "different promoters", "promoters and", "and use", "use different", "different reading", "reading frames", "quelle et", "et al.", "al. 1995", "1995 .", ". therefore", "while their", "their mrnas", "mrnas are", "are homologous", "homologous and", "and are", "are both", "both translationally", "translationally inhibited", "inhibited by", "by mir", "mir 24", "24 microrna", "lal et", "al. 2008", "to et", "al. 2012", "they share", "share no", "no similarity", "similarity at", "at the", "the amino", "amino acid", "acid sequence", "sequence level", "level and", "and perform", "perform distinct", "distinct functions", "functions in", "in the", "the cell.", "cell. p16ink4a", "p16ink4a acts", "acts as", "as the", "the inhibitor", "inhibitor of", "of cyclin", "cyclin dependent", "dependent kinases", "kinases cdk4", "cdk4 and", "and cdk6", "cdk6 which", "which phosphorylate", "phosphorylate and", "and inhibit", "inhibit rb1", "rb1 protein", "protein thereby", "thereby promoting", "promoting g1", "g1 to", "to s", "s transition", "transition and", "and cell", "cell cycle", "cycle progression", "serrano et", "al. 1993", "1993 .", ". increased", "increased p16ink4a", "p16ink4a level", "level leads", "leads to", "to hypophosphorylation", "hypophosphorylation of", "allowing rb1", "rb1 to", "to inhibit", "inhibit transcription", "e2f2 and", "and e2f3", "e2f3 target", "target genes", "genes that", "that are", "are needed", "needed for", "for cell", "which results", "results in", "in cell", "cycle arrest", "arrest in", "in g1", "g1 phase.", "phase. p14", "p14 arf", "arf binds", "binds and", "and destabilizes", "destabilizes mdm2", "mdm2 ubiquitin", "ubiquitin ligase", "zhang et", "al. 1998", "responsible for", "for ubiquitination", "ubiquitination and", "and degradation", "degradation of", "of tp53", "suppressor protein", "wu et", "fuchs et", "fang et", "al. 2000", "2000 .", "increased p14", "arf level", "to increased", "increased level", "tp53 and", "and increased", "increased expression", "expression of", "tp53 target", "as p21", "which triggers", "triggers p53", "p53 mediated", "mediated cell", "arrest and", "depending on", "on other", "other factors", "may also", "also lead", "lead to", "to p53", "mediated apoptosis.", "apoptosis. cdkn2b", "cdkn2b locus", "which encodes", "encodes an", "an inhibitor", "of cdk4", "is located", "located in", "the vicinity", "vicinity of", "the chromosome", "chromosome band", "band 9p21.", "9p21. p15ink4b", "together with", "with p16ink4a", "contributes to", "to senescence", "senescence of", "of human", "human t", "t lymphocytes", "erickson et", "and mouse", "mouse fibroblasts", "malumbres et", ". smad3", "activated by", "by tgf", "tgf beta", "beta 1", "1 signaling", "controls senescence", "senescence in", "the mouse", "mouse multistage", "multistage carcinogenesis", "carcinogenesis model", "model through", "through regulation", "regulation of", "of myc", "myc and", "and p15ink4b", "p15ink4b gene", "gene expression", "vijayachandra et", "al. 2003", "2003 .", ". tgf", "beta induced", "induced p15ink4b", "p15ink4b expression", "expression is", "is also", "also important", "important for", "for the", "the senescence", "of hepatocellular", "hepatocellular carcinoma", "carcinoma cell", "cell lines", "senturk et", "al. 2010", "2010 .

map", ".

map kinases", "kinases mapk1", "and mapk3", "which are", "are activated", "by ras", "ras signaling", "phosphorylate ets1", "ets1 and", "and ets2", "ets2 transcription", "transcription factors", "factors in", "the nucleus", "yang et", "al. 1996", "seidel et", "al. 2002", "foulds et", "al. 2004", "nelson et", "2010 .", ". phosphorylated", "phosphorylated ets1", "ets2 are", "are able", "able to", "to bind", "bind ras", "ras response", "response elements", "the cdkn2a", "locus and", "and stimulate", "stimulate p16ink4a", "p16ink4a transcription", "ohtani et", "2004 .", ". at", "the same", "same time", "activated erks", "mapk1 i.e.", "i.e. erk2", "erk2 and", "mapk3 i.e.", "i.e. erk1", "phosphorylate erf", "the repressor", "repressor of", "of ets2", "which leads", "to translocation", "translocation of", "of erf", "erf to", "to the", "the cytosol", "cytosol and", "increased transcription", "sgouras et", "le gallic", "gallic et", ". ets2", "ets2 can", "be sequestered", "sequestered and", "and inhibited", "by binding", "binding to", "to id1", "resulting in", "in inhibition", "inhibition of", "of p16ink4a", "2004 .

transcription", ".

transcription of", "of p14arf", "p14arf is", "is stimulated", "stimulated by", "binding of", "of e2f", "e2f transcription", "in complex", "complex with", "with sp1", "sp1 to", "to p14arf", "p14arf promoter", "parisi et", "2002 .

oncogenic", ".

oncogenic ras", "signaling affects", "affects mitochondrial", "mitochondrial metabolism", "metabolism through", "through an", "an unknown", "unknown mechanism", "leading to", "increased generation", "generation of", "of reactive", "reactive oxygen", "oxygen species", "triggers oxidative", "oxidative stress", "stress induced", "senescence pathway.", "pathway. in", "in addition", "increased rate", "rate of", "of cell", "cell division", "division that", "that is", "is one", "one of", "of the", "the consequences", "consequences of", "of oncogenic", "oncogenic signaling", "to telomere", "telomere shortening", "shortening which", "which acts", "as another", "another senescence", "senescence trigger.
while", "trigger.
while ois", "ois has", "has been", "been studied", "studied to", "to considerable", "considerable detail", "detail in", "in cultured", "cultured cells", "establishment of", "of in", "in vivo", "vivo role", "role of", "of ois", "been difficult", "difficult due", "due to", "to lack", "lack of", "of specific", "specific biomarkers", "biomarkers and", "and its", "its interconnectedness", "interconnectedness with", "with other", "other senescence", "senescence pathways", "baek and", "and ryeom", "ryeom 2017", "reviewed in", "in sharpless", "sharpless and", "and sherr", "sherr 2015", "2015 .", "senescence ois", "ois is", "is triggered by", "triggered by high", "by high level", "high level of", "level of ras/raf/mapk", "of ras/raf/mapk signaling", "ras/raf/mapk signaling that", "signaling that can", "that can be", "can be caused", "caused for", "example by", "by oncogenic mutations", "oncogenic mutations in", "mutations in ras", "in ras or", "ras or raf", "or raf proteins", "proteins or", "or by oncogenic", "mutations in growth", "in growth factor", "growth factor receptors", "receptors such", "such as egfr", "egfr that", "that act upstream", "act upstream of", "upstream of ras/raf/mapk", "of ras/raf/mapk cascade.", "ras/raf/mapk cascade. oncogene", "cascade. oncogene induced", "induced senescence can", "senescence can also", "can also be", "also be triggered", "be triggered by", "by high transcriptional", "high transcriptional activity", "transcriptional activity of", "activity of e2f1", "e2f1 e2f2", "e2f2 or e2f3", "or e2f3 which", "e2f3 which can", "which can be", "by the loss", "the loss of", "loss of function", "of function of", "function of rb1", "of rb1 tumor", "rb1 tumor suppressor.

oncogenic", "tumor suppressor.

oncogenic signals", "suppressor.

oncogenic signals trigger", "signals trigger transcription", "trigger transcription of", "transcription of cdkn2a", "of cdkn2a locus", "cdkn2a locus tumor", "locus tumor suppressor", "tumor suppressor genes:", "suppressor genes: p16ink4a", "genes: p16ink4a and", "p16ink4a and p14arf.", "and p14arf. p16ink4a", "p14arf. p16ink4a and", "p16ink4a and p14arf", "and p14arf share", "p14arf share exons", "share exons 2", "exons 2 and", "2 and 3", "3 but", "but are expressed", "are expressed from", "expressed from different", "from different promoters", "different promoters and", "promoters and use", "and use different", "use different reading", "different reading frames", "frames quelle", "quelle et al.", "et al. 1995", "al. 1995 .", "1995 . therefore", "therefore while", "while their mrnas", "their mrnas are", "mrnas are homologous", "are homologous and", "homologous and are", "and are both", "are both translationally", "both translationally inhibited", "translationally inhibited by", "inhibited by mir", "by mir 24", "mir 24 microrna", "microrna lal", "lal et al.", "et al. 2008", "2008 to", "to et al.", "et al. 2012", "they share no", "share no similarity", "no similarity at", "similarity at the", "at the amino", "the amino acid", "amino acid sequence", "acid sequence level", "sequence level and", "level and perform", "and perform distinct", "perform distinct functions", "distinct functions in", "functions in the", "in the cell.", "the cell. p16ink4a", "cell. p16ink4a acts", "p16ink4a acts as", "acts as the", "as the inhibitor", "the inhibitor of", "inhibitor of cyclin", "of cyclin dependent", "cyclin dependent kinases", "dependent kinases cdk4", "kinases cdk4 and", "cdk4 and cdk6", "and cdk6 which", "cdk6 which phosphorylate", "which phosphorylate and", "phosphorylate and inhibit", "and inhibit rb1", "inhibit rb1 protein", "rb1 protein thereby", "protein thereby promoting", "thereby promoting g1", "promoting g1 to", "g1 to s", "to s transition", "s transition and", "transition and cell", "and cell cycle", "cell cycle progression", "progression serrano", "serrano et al.", "et al. 1993", "al. 1993 .", "1993 . increased", ". increased p16ink4a", "increased p16ink4a level", "p16ink4a level leads", "level leads to", "leads to hypophosphorylation", "to hypophosphorylation of", "hypophosphorylation of rb1", "rb1 allowing", "allowing rb1 to", "rb1 to inhibit", "to inhibit transcription", "inhibit transcription of", "transcription of e2f1", "e2f2 and e2f3", "and e2f3 target", "e2f3 target genes", "target genes that", "genes that are", "that are needed", "are needed for", "needed for cell", "for cell cycle", "progression which", "which results in", "results in cell", "in cell cycle", "cell cycle arrest", "cycle arrest in", "arrest in g1", "in g1 phase.", "g1 phase. p14", "phase. p14 arf", "p14 arf binds", "arf binds and", "binds and destabilizes", "and destabilizes mdm2", "destabilizes mdm2 ubiquitin", "mdm2 ubiquitin ligase", "ligase zhang", "zhang et al.", "et al. 1998", "responsible for ubiquitination", "for ubiquitination and", "ubiquitination and degradation", "and degradation of", "degradation of tp53", "tp53 p53", "p53 tumor", "tumor suppressor protein", "protein wu", "wu et al.", "1993 fuchs", "fuchs et al.", "1998 fang", "fang et al.", "et al. 2000", "al. 2000 .", "2000 . therefore", "therefore increased", "increased p14 arf", "p14 arf level", "arf level leads", "leads to increased", "to increased level", "increased level of", "level of tp53", "of tp53 and", "tp53 and increased", "and increased expression", "increased expression of", "expression of tp53", "of tp53 target", "tp53 target genes", "genes such", "such as p21", "p21 which", "which triggers p53", "triggers p53 mediated", "p53 mediated cell", "mediated cell cycle", "cycle arrest and", "and depending", "depending on other", "on other factors", "factors may", "may also lead", "also lead to", "lead to p53", "to p53 mediated", "p53 mediated apoptosis.", "mediated apoptosis. cdkn2b", "apoptosis. cdkn2b locus", "locus which", "which encodes an", "encodes an inhibitor", "an inhibitor of", "inhibitor of cdk4", "of cdk4 and", "cdk6 p15ink4b", "p15ink4b is", "is located in", "located in the", "in the vicinity", "the vicinity of", "vicinity of cdkn2a", "locus at", "at the chromosome", "the chromosome band", "chromosome band 9p21.", "band 9p21. p15ink4b", "p15ink4b together", "together with p16ink4a", "p16ink4a contributes", "contributes to senescence", "to senescence of", "senescence of human", "of human t", "human t lymphocytes", "lymphocytes erickson", "erickson et al.", "1998 and", "and mouse fibroblasts", "fibroblasts malumbres", "malumbres et al.", "2000 . smad3", "smad3 activated", "activated by tgf", "by tgf beta", "tgf beta 1", "beta 1 signaling", "signaling controls", "controls senescence in", "senescence in the", "in the mouse", "the mouse multistage", "mouse multistage carcinogenesis", "multistage carcinogenesis model", "carcinogenesis model through", "model through regulation", "through regulation of", "regulation of myc", "of myc and", "myc and p15ink4b", "and p15ink4b gene", "p15ink4b gene expression", "expression vijayachandra", "vijayachandra et al.", "et al. 2003", "al. 2003 .", "2003 . tgf", ". tgf beta", "tgf beta induced", "beta induced p15ink4b", "induced p15ink4b expression", "p15ink4b expression is", "expression is also", "is also important", "also important for", "important for the", "for the senescence", "the senescence of", "senescence of hepatocellular", "of hepatocellular carcinoma", "hepatocellular carcinoma cell", "carcinoma cell lines", "lines senturk", "senturk et al.", "et al. 2010", "al. 2010 .

map", "2010 .

map kinases", ".

map kinases mapk1", "mapk1 erk2", "mapk3 erk1", "which are activated", "are activated by", "activated by ras", "by ras signaling", "signaling phosphorylate", "phosphorylate ets1 and", "ets1 and ets2", "and ets2 transcription", "ets2 transcription factors", "transcription factors in", "factors in the", "in the nucleus", "nucleus yang", "yang et al.", "et al. 1996", "1996 seidel", "seidel et al.", "et al. 2002", "2002 foulds", "foulds et al.", "et al. 2004", "2004 nelson", "nelson et al.", "al. 2010 .", "2010 . phosphorylated", ". phosphorylated ets1", "phosphorylated ets1 and", "and ets2 are", "ets2 are able", "are able to", "able to bind", "to bind ras", "bind ras response", "ras response elements", "elements rres", "rres in", "in the cdkn2a", "the cdkn2a locus", "cdkn2a locus and", "locus and stimulate", "and stimulate p16ink4a", "stimulate p16ink4a transcription", "transcription ohtani", "ohtani et al.", "al. 2004 .", "2004 . at", ". at the", "at the same", "the same time", "time activated", "erks mapk1", "mapk1 i.e. erk2", "i.e. erk2 and", "erk2 and mapk3", "and mapk3 i.e.", "mapk3 i.e. erk1", "erk1 phosphorylate", "erf the", "the repressor of", "repressor of ets2", "of ets2 transcription", "transcription which", "which leads to", "leads to translocation", "to translocation of", "translocation of erf", "of erf to", "erf to the", "to the cytosol", "the cytosol and", "cytosol and increased", "and increased transcription", "increased transcription of", "transcription of ets2", "ets2 sgouras", "sgouras et al.", "1995 le", "le gallic et", "gallic et al.", "2004 . ets2", ". ets2 can", "ets2 can be", "can be sequestered", "be sequestered and", "sequestered and inhibited", "and inhibited by", "inhibited by binding", "by binding to", "binding to id1", "id1 resulting", "resulting in inhibition", "in inhibition of", "inhibition of p16ink4a", "of p16ink4a transcription", "al. 2004 .

transcription", "2004 .

transcription of", ".

transcription of p14arf", "of p14arf is", "p14arf is stimulated", "is stimulated by", "stimulated by binding", "by binding of", "binding of e2f", "of e2f transcription", "e2f transcription factors", "factors e2f1", "e2f3 in", "in complex with", "complex with sp1", "with sp1 to", "sp1 to p14arf", "to p14arf promoter", "promoter parisi", "parisi et al.", "al. 2002 .

oncogenic", "2002 .

oncogenic ras", ".

oncogenic ras signaling", "ras signaling affects", "signaling affects mitochondrial", "affects mitochondrial metabolism", "mitochondrial metabolism through", "metabolism through an", "through an unknown", "an unknown mechanism", "mechanism leading", "leading to increased", "to increased generation", "increased generation of", "generation of reactive", "of reactive oxygen", "reactive oxygen species", "species ros", "which triggers oxidative", "triggers oxidative stress", "oxidative stress induced", "stress induced senescence", "induced senescence pathway.", "senescence pathway. in", "pathway. in addition", "addition increased", "increased rate of", "rate of cell", "of cell division", "cell division that", "division that is", "that is one", "is one of", "one of the", "of the consequences", "the consequences of", "consequences of oncogenic", "of oncogenic signaling", "signaling leads", "leads to telomere", "to telomere shortening", "telomere shortening which", "shortening which acts", "which acts as", "acts as another", "as another senescence", "another senescence trigger.
while", "senescence trigger.
while ois", "trigger.
while ois has", "ois has been", "has been studied", "been studied to", "studied to considerable", "to considerable detail", "considerable detail in", "detail in cultured", "in cultured cells", "cells establishment", "establishment of in", "of in vivo", "in vivo role", "vivo role of", "role of ois", "of ois has", "has been difficult", "been difficult due", "difficult due to", "due to lack", "to lack of", "lack of specific", "of specific biomarkers", "specific biomarkers and", "biomarkers and its", "and its interconnectedness", "its interconnectedness with", "interconnectedness with other", "with other senescence", "other senescence pathways", "pathways baek", "baek and ryeom", "and ryeom 2017", "2017 reviewed", "reviewed in sharpless", "in sharpless and", "sharpless and sherr", "and sherr 2015", "sherr 2015 .", "induced senescence ois", "ois is triggered", "is triggered by high", "triggered by high level", "by high level of", "high level of ras/raf/mapk", "level of ras/raf/mapk signaling", "of ras/raf/mapk signaling that", "ras/raf/mapk signaling that can", "signaling that can be", "that can be caused", "be caused for", "caused for example", "for example by", "example by oncogenic", "by oncogenic mutations in", "oncogenic mutations in ras", "mutations in ras or", "in ras or raf", "ras or raf proteins", "raf proteins or", "proteins or by", "or by oncogenic mutations", "oncogenic mutations in growth", "mutations in growth factor", "in growth factor receptors", "factor receptors such", "receptors such as", "as egfr that", "egfr that act", "that act upstream of", "act upstream of ras/raf/mapk", "upstream of ras/raf/mapk cascade.", "of ras/raf/mapk cascade. oncogene", "ras/raf/mapk cascade. oncogene induced", "cascade. oncogene induced senescence", "oncogene induced senescence can", "induced senescence can also", "senescence can also be", "can also be triggered", "also be triggered by", "be triggered by high", "triggered by high transcriptional", "by high transcriptional activity", "high transcriptional activity of", "transcriptional activity of e2f1", "of e2f1 e2f2", "e2f1 e2f2 or", "e2f2 or e2f3 which", "or e2f3 which can", "e2f3 which can be", "which can be caused", "example by the", "by the loss of", "the loss of function", "loss of function of", "of function of rb1", "function of rb1 tumor", "of rb1 tumor suppressor.

oncogenic", "rb1 tumor suppressor.

oncogenic signals", "tumor suppressor.

oncogenic signals trigger", "suppressor.

oncogenic signals trigger transcription", "signals trigger transcription of", "trigger transcription of cdkn2a", "transcription of cdkn2a locus", "of cdkn2a locus tumor", "cdkn2a locus tumor suppressor", "locus tumor suppressor genes:", "tumor suppressor genes: p16ink4a", "suppressor genes: p16ink4a and", "genes: p16ink4a and p14arf.", "p16ink4a and p14arf. p16ink4a", "and p14arf. p16ink4a and", "p14arf. p16ink4a and p14arf", "p16ink4a and p14arf share", "and p14arf share exons", "p14arf share exons 2", "share exons 2 and", "exons 2 and 3", "and 3 but", "3 but are", "but are expressed from", "are expressed from different", "expressed from different promoters", "from different promoters and", "different promoters and use", "promoters and use different", "and use different reading", "use different reading frames", "reading frames quelle", "frames quelle et", "quelle et al. 1995", "et al. 1995 .", "al. 1995 . therefore", ". therefore while", "therefore while their", "while their mrnas are", "their mrnas are homologous", "mrnas are homologous and", "are homologous and are", "homologous and are both", "and are both translationally", "are both translationally inhibited", "both translationally inhibited by", "translationally inhibited by mir", "inhibited by mir 24", "by mir 24 microrna", "24 microrna lal", "microrna lal et", "lal et al. 2008", "al. 2008 to", "2008 to et", "to et al. 2012", "2012 they", "they share no similarity", "share no similarity at", "no similarity at the", "similarity at the amino", "at the amino acid", "the amino acid sequence", "amino acid sequence level", "acid sequence level and", "sequence level and perform", "level and perform distinct", "and perform distinct functions", "perform distinct functions in", "distinct functions in the", "functions in the cell.", "in the cell. p16ink4a", "the cell. p16ink4a acts", "cell. p16ink4a acts as", "p16ink4a acts as the", "acts as the inhibitor", "as the inhibitor of", "the inhibitor of cyclin", "inhibitor of cyclin dependent", "of cyclin dependent kinases", "cyclin dependent kinases cdk4", "dependent kinases cdk4 and", "kinases cdk4 and cdk6", "cdk4 and cdk6 which", "and cdk6 which phosphorylate", "cdk6 which phosphorylate and", "which phosphorylate and inhibit", "phosphorylate and inhibit rb1", "and inhibit rb1 protein", "inhibit rb1 protein thereby", "rb1 protein thereby promoting", "protein thereby promoting g1", "thereby promoting g1 to", "promoting g1 to s", "g1 to s transition", "to s transition and", "s transition and cell", "transition and cell cycle", "and cell cycle progression", "cycle progression serrano", "progression serrano et", "serrano et al. 1993", "et al. 1993 .", "al. 1993 . increased", "1993 . increased p16ink4a", ". increased p16ink4a level", "increased p16ink4a level leads", "p16ink4a level leads to", "level leads to hypophosphorylation", "leads to hypophosphorylation of", "to hypophosphorylation of rb1", "of rb1 allowing", "rb1 allowing rb1", "allowing rb1 to inhibit", "rb1 to inhibit transcription", "to inhibit transcription of", "inhibit transcription of e2f1", "e2f1 e2f2 and", "e2f2 and e2f3 target", "and e2f3 target genes", "e2f3 target genes that", "target genes that are", "genes that are needed", "that are needed for", "are needed for cell", "needed for cell cycle", "for cell cycle progression", "cycle progression which", "progression which results", "which results in cell", "results in cell cycle", "in cell cycle arrest", "cell cycle arrest in", "cycle arrest in g1", "arrest in g1 phase.", "in g1 phase. p14", "g1 phase. p14 arf", "phase. p14 arf binds", "p14 arf binds and", "arf binds and destabilizes", "binds and destabilizes mdm2", "and destabilizes mdm2 ubiquitin", "destabilizes mdm2 ubiquitin ligase", "ubiquitin ligase zhang", "ligase zhang et", "zhang et al. 1998", "1998 responsible", "responsible for ubiquitination and", "for ubiquitination and degradation", "ubiquitination and degradation of", "and degradation of tp53", "of tp53 p53", "p53 tumor suppressor", "suppressor protein wu", "protein wu et", "wu et al. 1993", "al. 1993 fuchs", "1993 fuchs et", "fuchs et al. 1998", "al. 1998 fang", "1998 fang et", "fang et al. 2000", "et al. 2000 .", "al. 2000 . therefore", ". therefore increased", "therefore increased p14", "increased p14 arf level", "p14 arf level leads", "arf level leads to", "level leads to increased", "leads to increased level", "to increased level of", "increased level of tp53", "level of tp53 and", "of tp53 and increased", "tp53 and increased expression", "and increased expression of", "increased expression of tp53", "expression of tp53 target", "of tp53 target genes", "target genes such", "genes such as", "as p21 which", "p21 which triggers", "which triggers p53 mediated", "triggers p53 mediated cell", "p53 mediated cell cycle", "mediated cell cycle arrest", "cell cycle arrest and", "arrest and depending", "and depending on", "depending on other factors", "other factors may", "factors may also", "may also lead to", "also lead to p53", "lead to p53 mediated", "to p53 mediated apoptosis.", "p53 mediated apoptosis. cdkn2b", "mediated apoptosis. cdkn2b locus", "cdkn2b locus which", "locus which encodes", "which encodes an inhibitor", "encodes an inhibitor of", "an inhibitor of cdk4", "inhibitor of cdk4 and", "of cdk4 and cdk6", "and cdk6 p15ink4b", "p15ink4b is located", "is located in the", "located in the vicinity", "in the vicinity of", "the vicinity of cdkn2a", "vicinity of cdkn2a locus", "cdkn2a locus at", "locus at the", "at the chromosome band", "the chromosome band 9p21.", "chromosome band 9p21. p15ink4b", "9p21. p15ink4b together", "p15ink4b together with", "with p16ink4a contributes", "p16ink4a contributes to", "contributes to senescence of", "to senescence of human", "senescence of human t", "of human t lymphocytes", "t lymphocytes erickson", "lymphocytes erickson et", "erickson et al. 1998", "al. 1998 and", "1998 and mouse", "mouse fibroblasts malumbres", "fibroblasts malumbres et", "malumbres et al. 2000", "al. 2000 . smad3", ". smad3 activated", "smad3 activated by", "activated by tgf beta", "by tgf beta 1", "tgf beta 1 signaling", "1 signaling controls", "signaling controls senescence", "controls senescence in the", "senescence in the mouse", "in the mouse multistage", "the mouse multistage carcinogenesis", "mouse multistage carcinogenesis model", "multistage carcinogenesis model through", "carcinogenesis model through regulation", "model through regulation of", "through regulation of myc", "regulation of myc and", "of myc and p15ink4b", "myc and p15ink4b gene", "and p15ink4b gene expression", "gene expression vijayachandra", "expression vijayachandra et", "vijayachandra et al. 2003", "et al. 2003 .", "al. 2003 . tgf", "2003 . tgf beta", ". tgf beta induced", "tgf beta induced p15ink4b", "beta induced p15ink4b expression", "induced p15ink4b expression is", "p15ink4b expression is also", "expression is also important", "is also important for", "also important for the", "important for the senescence", "for the senescence of", "the senescence of hepatocellular", "senescence of hepatocellular carcinoma", "of hepatocellular carcinoma cell", "hepatocellular carcinoma cell lines", "cell lines senturk", "lines senturk et", "senturk et al. 2010", "et al. 2010 .

map", "al. 2010 .

map kinases", "2010 .

map kinases mapk1", "kinases mapk1 erk2", "and mapk3 erk1", "erk1 which", "which are activated by", "are activated by ras", "activated by ras signaling", "ras signaling phosphorylate", "signaling phosphorylate ets1", "phosphorylate ets1 and ets2", "ets1 and ets2 transcription", "and ets2 transcription factors", "ets2 transcription factors in", "transcription factors in the", "factors in the nucleus", "the nucleus yang", "nucleus yang et", "yang et al. 1996", "al. 1996 seidel", "1996 seidel et", "seidel et al. 2002", "al. 2002 foulds", "2002 foulds et", "foulds et al. 2004", "al. 2004 nelson", "2004 nelson et", "nelson et al. 2010", "et al. 2010 .", "al. 2010 . phosphorylated", "2010 . phosphorylated ets1", ". phosphorylated ets1 and", "phosphorylated ets1 and ets2", "ets1 and ets2 are", "and ets2 are able", "ets2 are able to", "are able to bind", "able to bind ras", "to bind ras response", "bind ras response elements", "response elements rres", "rres in the", "in the cdkn2a locus", "the cdkn2a locus and", "cdkn2a locus and stimulate", "locus and stimulate p16ink4a", "and stimulate p16ink4a transcription", "p16ink4a transcription ohtani", "transcription ohtani et", "ohtani et al. 2004", "et al. 2004 .", "al. 2004 . at", "2004 . at the", ". at the same", "at the same time", "same time activated", "time activated erks", "activated erks mapk1", "erks mapk1 i.e.", "mapk1 i.e. erk2 and", "i.e. erk2 and mapk3", "erk2 and mapk3 i.e.", "and mapk3 i.e. erk1", "i.e. erk1 phosphorylate", "erk1 phosphorylate erf", "phosphorylate erf the", "erf the repressor", "the repressor of ets2", "repressor of ets2 transcription", "ets2 transcription which", "transcription which leads", "which leads to translocation", "leads to translocation of", "to translocation of erf", "translocation of erf to", "of erf to the", "erf to the cytosol", "to the cytosol and", "the cytosol and increased", "cytosol and increased transcription", "and increased transcription of", "increased transcription of ets2", "of ets2 sgouras", "ets2 sgouras et", "sgouras et al. 1995", "al. 1995 le", "1995 le gallic", "le gallic et al.", "gallic et al. 2004", "al. 2004 . ets2", "2004 . ets2 can", ". ets2 can be", "ets2 can be sequestered", "can be sequestered and", "be sequestered and inhibited", "sequestered and inhibited by", "and inhibited by binding", "inhibited by binding to", "by binding to id1", "to id1 resulting", "id1 resulting in", "resulting in inhibition of", "in inhibition of p16ink4a", "inhibition of p16ink4a transcription", "et al. 2004 .

transcription", "al. 2004 .

transcription of", "2004 .

transcription of p14arf", ".

transcription of p14arf is", "of p14arf is stimulated", "p14arf is stimulated by", "is stimulated by binding", "stimulated by binding of", "by binding of e2f", "binding of e2f transcription", "of e2f transcription factors", "transcription factors e2f1", "or e2f3 in", "e2f3 in complex", "in complex with sp1", "complex with sp1 to", "with sp1 to p14arf", "sp1 to p14arf promoter", "p14arf promoter parisi", "promoter parisi et", "parisi et al. 2002", "et al. 2002 .

oncogenic", "al. 2002 .

oncogenic ras", "2002 .

oncogenic ras signaling", ".

oncogenic ras signaling affects", "ras signaling affects mitochondrial", "signaling affects mitochondrial metabolism", "affects mitochondrial metabolism through", "mitochondrial metabolism through an", "metabolism through an unknown", "through an unknown mechanism", "unknown mechanism leading", "mechanism leading to", "leading to increased generation", "to increased generation of", "increased generation of reactive", "generation of reactive oxygen", "of reactive oxygen species", "oxygen species ros", "ros which", "which triggers oxidative stress", "triggers oxidative stress induced", "oxidative stress induced senescence", "stress induced senescence pathway.", "induced senescence pathway. in", "senescence pathway. in addition", "in addition increased", "addition increased rate", "increased rate of cell", "rate of cell division", "of cell division that", "cell division that is", "division that is one", "that is one of", "is one of the", "one of the consequences", "of the consequences of", "the consequences of oncogenic", "consequences of oncogenic signaling", "oncogenic signaling leads", "signaling leads to", "leads to telomere shortening", "to telomere shortening which", "telomere shortening which acts", "shortening which acts as", "which acts as another", "acts as another senescence", "as another senescence trigger.
while", "another senescence trigger.
while ois", "senescence trigger.
while ois has", "trigger.
while ois has been", "ois has been studied", "has been studied to", "been studied to considerable", "studied to considerable detail", "to considerable detail in", "considerable detail in cultured", "detail in cultured cells", "cultured cells establishment", "cells establishment of", "establishment of in vivo", "of in vivo role", "in vivo role of", "vivo role of ois", "role of ois has", "of ois has been", "ois has been difficult", "has been difficult due", "been difficult due to", "difficult due to lack", "due to lack of", "to lack of specific", "lack of specific biomarkers", "of specific biomarkers and", "specific biomarkers and its", "biomarkers and its interconnectedness", "and its interconnectedness with", "its interconnectedness with other", "interconnectedness with other senescence", "with other senescence pathways", "senescence pathways baek", "pathways baek and", "baek and ryeom 2017", "ryeom 2017 reviewed", "2017 reviewed in", "reviewed in sharpless and", "in sharpless and sherr", "sharpless and sherr 2015", "and sherr 2015 .", "oncogene induced senescence ois", "senescence ois is", "ois is triggered by", "is triggered by high level", "triggered by high level of", "by high level of ras/raf/mapk", "high level of ras/raf/mapk signaling", "level of ras/raf/mapk signaling that", "of ras/raf/mapk signaling that can", "ras/raf/mapk signaling that can be", "signaling that can be caused", "can be caused for", "be caused for example", "for example by oncogenic", "example by oncogenic mutations", "by oncogenic mutations in ras", "oncogenic mutations in ras or", "mutations in ras or raf", "in ras or raf proteins", "or raf proteins or", "raf proteins or by", "proteins or by oncogenic", "or by oncogenic mutations in", "by oncogenic mutations in growth", "oncogenic mutations in growth factor", "mutations in growth factor receptors", "growth factor receptors such", "factor receptors such as", "receptors such as egfr", "such as egfr that", "as egfr that act", "egfr that act upstream", "that act upstream of ras/raf/mapk", "act upstream of ras/raf/mapk cascade.", "upstream of ras/raf/mapk cascade. oncogene", "of ras/raf/mapk cascade. oncogene induced", "ras/raf/mapk cascade. oncogene induced senescence", "cascade. oncogene induced senescence can", "oncogene induced senescence can also", "induced senescence can also be", "senescence can also be triggered", "can also be triggered by", "also be triggered by high", "be triggered by high transcriptional", "triggered by high transcriptional activity", "by high transcriptional activity of", "high transcriptional activity of e2f1", "activity of e2f1 e2f2", "of e2f1 e2f2 or", "e2f1 e2f2 or e2f3", "e2f2 or e2f3 which can", "or e2f3 which can be", "e2f3 which can be caused", "for example by the", "example by the loss", "by the loss of function", "the loss of function of", "loss of function of rb1", "of function of rb1 tumor", "function of rb1 tumor suppressor.

oncogenic", "of rb1 tumor suppressor.

oncogenic signals", "rb1 tumor suppressor.

oncogenic signals trigger", "tumor suppressor.

oncogenic signals trigger transcription", "suppressor.

oncogenic signals trigger transcription of", "signals trigger transcription of cdkn2a", "trigger transcription of cdkn2a locus", "transcription of cdkn2a locus tumor", "of cdkn2a locus tumor suppressor", "cdkn2a locus tumor suppressor genes:", "locus tumor suppressor genes: p16ink4a", "tumor suppressor genes: p16ink4a and", "suppressor genes: p16ink4a and p14arf.", "genes: p16ink4a and p14arf. p16ink4a", "p16ink4a and p14arf. p16ink4a and", "and p14arf. p16ink4a and p14arf", "p14arf. p16ink4a and p14arf share", "p16ink4a and p14arf share exons", "and p14arf share exons 2", "p14arf share exons 2 and", "share exons 2 and 3", "2 and 3 but", "and 3 but are", "3 but are expressed", "but are expressed from different", "are expressed from different promoters", "expressed from different promoters and", "from different promoters and use", "different promoters and use different", "promoters and use different reading", "and use different reading frames", "different reading frames quelle", "reading frames quelle et", "frames quelle et al.", "quelle et al. 1995 .", "et al. 1995 . therefore", "1995 . therefore while", ". therefore while their", "therefore while their mrnas", "while their mrnas are homologous", "their mrnas are homologous and", "mrnas are homologous and are", "are homologous and are both", "homologous and are both translationally", "and are both translationally inhibited", "are both translationally inhibited by", "both translationally inhibited by mir", "translationally inhibited by mir 24", "inhibited by mir 24 microrna", "mir 24 microrna lal", "24 microrna lal et", "microrna lal et al.", "et al. 2008 to", "al. 2008 to et", "2008 to et al.", "al. 2012 they", "2012 they share", "they share no similarity at", "share no similarity at the", "no similarity at the amino", "similarity at the amino acid", "at the amino acid sequence", "the amino acid sequence level", "amino acid sequence level and", "acid sequence level and perform", "sequence level and perform distinct", "level and perform distinct functions", "and perform distinct functions in", "perform distinct functions in the", "distinct functions in the cell.", "functions in the cell. p16ink4a", "in the cell. p16ink4a acts", "the cell. p16ink4a acts as", "cell. p16ink4a acts as the", "p16ink4a acts as the inhibitor", "acts as the inhibitor of", "as the inhibitor of cyclin", "the inhibitor of cyclin dependent", "inhibitor of cyclin dependent kinases", "of cyclin dependent kinases cdk4", "cyclin dependent kinases cdk4 and", "dependent kinases cdk4 and cdk6", "kinases cdk4 and cdk6 which", "cdk4 and cdk6 which phosphorylate", "and cdk6 which phosphorylate and", "cdk6 which phosphorylate and inhibit", "which phosphorylate and inhibit rb1", "phosphorylate and inhibit rb1 protein", "and inhibit rb1 protein thereby", "inhibit rb1 protein thereby promoting", "rb1 protein thereby promoting g1", "protein thereby promoting g1 to", "thereby promoting g1 to s", "promoting g1 to s transition", "g1 to s transition and", "to s transition and cell", "s transition and cell cycle", "transition and cell cycle progression", "cell cycle progression serrano", "cycle progression serrano et", "progression serrano et al.", "serrano et al. 1993 .", "et al. 1993 . increased", "al. 1993 . increased p16ink4a", "1993 . increased p16ink4a level", ". increased p16ink4a level leads", "increased p16ink4a level leads to", "p16ink4a level leads to hypophosphorylation", "level leads to hypophosphorylation of", "leads to hypophosphorylation of rb1", "hypophosphorylation of rb1 allowing", "of rb1 allowing rb1", "rb1 allowing rb1 to", "allowing rb1 to inhibit transcription", "rb1 to inhibit transcription of", "to inhibit transcription of e2f1", "transcription of e2f1 e2f2", "of e2f1 e2f2 and", "e2f1 e2f2 and e2f3", "e2f2 and e2f3 target genes", "and e2f3 target genes that", "e2f3 target genes that are", "target genes that are needed", "genes that are needed for", "that are needed for cell", "are needed for cell cycle", "needed for cell cycle progression", "cell cycle progression which", "cycle progression which results", "progression which results in", "which results in cell cycle", "results in cell cycle arrest", "in cell cycle arrest in", "cell cycle arrest in g1", "cycle arrest in g1 phase.", "arrest in g1 phase. p14", "in g1 phase. p14 arf", "g1 phase. p14 arf binds", "phase. p14 arf binds and", "p14 arf binds and destabilizes", "arf binds and destabilizes mdm2", "binds and destabilizes mdm2 ubiquitin", "and destabilizes mdm2 ubiquitin ligase", "mdm2 ubiquitin ligase zhang", "ubiquitin ligase zhang et", "ligase zhang et al.", "al. 1998 responsible", "1998 responsible for", "responsible for ubiquitination and degradation", "for ubiquitination and degradation of", "ubiquitination and degradation of tp53", "degradation of tp53 p53", "tp53 p53 tumor", "p53 tumor suppressor protein", "tumor suppressor protein wu", "suppressor protein wu et", "protein wu et al.", "et al. 1993 fuchs", "al. 1993 fuchs et", "1993 fuchs et al.", "et al. 1998 fang", "al. 1998 fang et", "1998 fang et al.", "fang et al. 2000 .", "et al. 2000 . therefore", "2000 . therefore increased", ". therefore increased p14", "therefore increased p14 arf", "increased p14 arf level leads", "p14 arf level leads to", "arf level leads to increased", "level leads to increased level", "leads to increased level of", "to increased level of tp53", "increased level of tp53 and", "level of tp53 and increased", "of tp53 and increased expression", "tp53 and increased expression of", "and increased expression of tp53", "increased expression of tp53 target", "expression of tp53 target genes", "tp53 target genes such", "target genes such as", "genes such as p21", "such as p21 which", "as p21 which triggers", "p21 which triggers p53", "which triggers p53 mediated cell", "triggers p53 mediated cell cycle", "p53 mediated cell cycle arrest", "mediated cell cycle arrest and", "cycle arrest and depending", "arrest and depending on", "and depending on other", "on other factors may", "other factors may also", "factors may also lead", "may also lead to p53", "also lead to p53 mediated", "lead to p53 mediated apoptosis.", "to p53 mediated apoptosis. cdkn2b", "p53 mediated apoptosis. cdkn2b locus", "apoptosis. cdkn2b locus which", "cdkn2b locus which encodes", "locus which encodes an", "which encodes an inhibitor of", "encodes an inhibitor of cdk4", "an inhibitor of cdk4 and", "inhibitor of cdk4 and cdk6", "cdk4 and cdk6 p15ink4b", "cdk6 p15ink4b is", "p15ink4b is located in", "is located in the vicinity", "located in the vicinity of", "in the vicinity of cdkn2a", "the vicinity of cdkn2a locus", "of cdkn2a locus at", "cdkn2a locus at the", "locus at the chromosome", "at the chromosome band 9p21.", "the chromosome band 9p21. p15ink4b", "band 9p21. p15ink4b together", "9p21. p15ink4b together with", "p15ink4b together with p16ink4a", "together with p16ink4a contributes", "with p16ink4a contributes to", "p16ink4a contributes to senescence", "contributes to senescence of human", "to senescence of human t", "senescence of human t lymphocytes", "human t lymphocytes erickson", "t lymphocytes erickson et", "lymphocytes erickson et al.", "et al. 1998 and", "al. 1998 and mouse", "1998 and mouse fibroblasts", "and mouse fibroblasts malumbres", "mouse fibroblasts malumbres et", "fibroblasts malumbres et al.", "malumbres et al. 2000 .", "et al. 2000 . smad3", "2000 . smad3 activated", ". smad3 activated by", "smad3 activated by tgf", "activated by tgf beta 1", "by tgf beta 1 signaling", "beta 1 signaling controls", "1 signaling controls senescence", "signaling controls senescence in", "controls senescence in the mouse", "senescence in the mouse multistage", "in the mouse multistage carcinogenesis", "the mouse multistage carcinogenesis model", "mouse multistage carcinogenesis model through", "multistage carcinogenesis model through regulation", "carcinogenesis model through regulation of", "model through regulation of myc", "through regulation of myc and", "regulation of myc and p15ink4b", "of myc and p15ink4b gene", "myc and p15ink4b gene expression", "p15ink4b gene expression vijayachandra", "gene expression vijayachandra et", "expression vijayachandra et al.", "vijayachandra et al. 2003 .", "et al. 2003 . tgf", "al. 2003 . tgf beta", "2003 . tgf beta induced", ". tgf beta induced p15ink4b", "tgf beta induced p15ink4b expression", "beta induced p15ink4b expression is", "induced p15ink4b expression is also", "p15ink4b expression is also important", "expression is also important for", "is also important for the", "also important for the senescence", "important for the senescence of", "for the senescence of hepatocellular", "the senescence of hepatocellular carcinoma", "senescence of hepatocellular carcinoma cell", "of hepatocellular carcinoma cell lines", "carcinoma cell lines senturk", "cell lines senturk et", "lines senturk et al.", "senturk et al. 2010 .

map", "et al. 2010 .

map kinases", "al. 2010 .

map kinases mapk1", ".

map kinases mapk1 erk2", "mapk1 erk2 and", "erk1 which are", "which are activated by ras", "are activated by ras signaling", "by ras signaling phosphorylate", "ras signaling phosphorylate ets1", "signaling phosphorylate ets1 and", "phosphorylate ets1 and ets2 transcription", "ets1 and ets2 transcription factors", "and ets2 transcription factors in", "ets2 transcription factors in the", "transcription factors in the nucleus", "in the nucleus yang", "the nucleus yang et", "nucleus yang et al.", "et al. 1996 seidel", "al. 1996 seidel et", "1996 seidel et al.", "et al. 2002 foulds", "al. 2002 foulds et", "2002 foulds et al.", "et al. 2004 nelson", "al. 2004 nelson et", "2004 nelson et al.", "nelson et al. 2010 .", "et al. 2010 . phosphorylated", "al. 2010 . phosphorylated ets1", "2010 . phosphorylated ets1 and", ". phosphorylated ets1 and ets2", "phosphorylated ets1 and ets2 are", "ets1 and ets2 are able", "and ets2 are able to", "ets2 are able to bind", "are able to bind ras", "able to bind ras response", "to bind ras response elements", "ras response elements rres", "elements rres in", "rres in the cdkn2a", "in the cdkn2a locus and", "the cdkn2a locus and stimulate", "cdkn2a locus and stimulate p16ink4a", "locus and stimulate p16ink4a transcription", "stimulate p16ink4a transcription ohtani", "p16ink4a transcription ohtani et", "transcription ohtani et al.", "ohtani et al. 2004 .", "et al. 2004 . at", "al. 2004 . at the", "2004 . at the same", ". at the same time", "the same time activated", "same time activated erks", "activated erks mapk1 i.e.", "erks mapk1 i.e. erk2", "mapk1 i.e. erk2 and mapk3", "i.e. erk2 and mapk3 i.e.", "erk2 and mapk3 i.e. erk1", "mapk3 i.e. erk1 phosphorylate", "i.e. erk1 phosphorylate erf", "phosphorylate erf the repressor", "erf the repressor of", "the repressor of ets2 transcription", "of ets2 transcription which", "ets2 transcription which leads", "transcription which leads to", "which leads to translocation of", "leads to translocation of erf", "to translocation of erf to", "translocation of erf to the", "of erf to the cytosol", "erf to the cytosol and", "to the cytosol and increased", "the cytosol and increased transcription", "cytosol and increased transcription of", "and increased transcription of ets2", "transcription of ets2 sgouras", "of ets2 sgouras et", "ets2 sgouras et al.", "et al. 1995 le", "al. 1995 le gallic", "1995 le gallic et", "le gallic et al. 2004", "gallic et al. 2004 .", "et al. 2004 . ets2", "al. 2004 . ets2 can", "2004 . ets2 can be", ". ets2 can be sequestered", "ets2 can be sequestered and", "can be sequestered and inhibited", "be sequestered and inhibited by", "sequestered and inhibited by binding", "and inhibited by binding to", "inhibited by binding to id1", "binding to id1 resulting", "to id1 resulting in", "id1 resulting in inhibition", "resulting in inhibition of p16ink4a", "in inhibition of p16ink4a transcription", "of p16ink4a transcription ohtani", "ohtani et al. 2004 .

transcription", "et al. 2004 .

transcription of", "al. 2004 .

transcription of p14arf", "2004 .

transcription of p14arf is", ".

transcription of p14arf is stimulated", "of p14arf is stimulated by", "p14arf is stimulated by binding", "is stimulated by binding of", "stimulated by binding of e2f", "by binding of e2f transcription", "binding of e2f transcription factors", "e2f transcription factors e2f1", "factors e2f1 e2f2", "e2f2 or e2f3 in", "or e2f3 in complex", "e2f3 in complex with", "in complex with sp1 to", "complex with sp1 to p14arf", "with sp1 to p14arf promoter", "to p14arf promoter parisi", "p14arf promoter parisi et", "promoter parisi et al.", "parisi et al. 2002 .

oncogenic", "et al. 2002 .

oncogenic ras", "al. 2002 .

oncogenic ras signaling", "2002 .

oncogenic ras signaling affects", ".

oncogenic ras signaling affects mitochondrial", "ras signaling affects mitochondrial metabolism", "signaling affects mitochondrial metabolism through", "affects mitochondrial metabolism through an", "mitochondrial metabolism through an unknown", "metabolism through an unknown mechanism", "an unknown mechanism leading", "unknown mechanism leading to", "mechanism leading to increased", "leading to increased generation of", "to increased generation of reactive", "increased generation of reactive oxygen", "generation of reactive oxygen species", "reactive oxygen species ros", "ros which triggers", "which triggers oxidative stress induced", "triggers oxidative stress induced senescence", "oxidative stress induced senescence pathway.", "stress induced senescence pathway. in", "induced senescence pathway. in addition", "pathway. in addition increased", "in addition increased rate", "addition increased rate of", "increased rate of cell division", "rate of cell division that", "of cell division that is", "cell division that is one", "division that is one of", "that is one of the", "is one of the consequences", "one of the consequences of", "of the consequences of oncogenic", "the consequences of oncogenic signaling", "of oncogenic signaling leads", "oncogenic signaling leads to", "signaling leads to telomere", "leads to telomere shortening which", "to telomere shortening which acts", "telomere shortening which acts as", "shortening which acts as another", "which acts as another senescence", "acts as another senescence trigger.
while", "as another senescence trigger.
while ois", "another senescence trigger.
while ois has", "senescence trigger.
while ois has been", "trigger.
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the", "

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the", ".
the identification", "identification of", "of spontaneous", "spontaneous mutations", "mutations in", "in the", "the leptin", "leptin gene", "ob or", "or lep", "and the", "leptin receptor", "receptor gene", "ob r", "db or", "or lepr", "genes in", "in mice", "mice opened", "opened up", "up a", "a new", "new field", "field in", "obesity research.", "research. leptin", "leptin was", "was discovered", "discovered as", "as the", "the product", "product of", "of the", "the gene", "gene affected", "affected by", "by the", "the ob", "which causes", "causes obesity", "obesity in", "in mice.", "mice. likewise", "likewise lepr", "lepr is", "is the", "the db", "mutation. leptin", "leptin binding", "binding to", "to lepr", "lepr induces", "induces canonical", "mapk/erk 1/2", "pi 3k/akt", "and non", "non canonical", "canonical signaling", "signaling pathways", "p38 mapk", "mapk and", "and ampk", "in diverse", "diverse cell", "cell types.", "types. the", "the binding", "binding of", "of leptin", "leptin to", "to the", "the long", "long isoform", "isoform of", "of lepr", "ob rl", "initiates a", "a phosphorylation", "phosphorylation cascade", "cascade that", "that results", "results in", "in transcriptional", "transcriptional activation", "activation of", "of target", "target genes", "genes by", "by stat5", "stat5 and", "and stat3", "stat3 and", "and activation", "the pi3k", "pi3k pathway", "pathway not", "not shown", "shown here", "the mapk/erk", "mapk/erk pathway", "the mtor/s6k", "mtor/s6k pathway.", "pathway. shorter", "shorter lepr", "lepr isoforms", "isoforms with", "with truncated", "truncated intracellular", "intracellular domains", "domains are", "are unable", "unable to", "to activate", "activate the", "the stat", "stat pathway", "but can", "can transduce", "transduce signals", "signals by", "by way", "way of", "of activation", "of jak2", "irs 1", "1 or", "or erks", "including mapks.
lepr", "mapks.
lepr is", "is constitutively", "constitutively bound", "bound to", "the jak2", "jak2 kinase.", "kinase. binding", "of lep", "lep to", "lepr causes", "causes a", "a conformational", "conformational change", "change in", "in lepr", "lepr that", "that activates", "activates jak2", "jak2 autophosphorylation", "autophosphorylation followed", "followed by", "by phosphorylation", "phosphorylation of", "lepr by", "by jak2.", "jak2. phosphorylated", "phosphorylated lepr", "lepr binds", "binds stat3", "and shp2", "shp2 which", "which are", "are then", "then phosphorylated", "phosphorylated by", "phosphorylated jak2", "jak2 binds", "binds sh2b1", "sh2b1 which", "which then", "then binds", "binds irs1/2", "resulting in", "in phosphorylation", "of irs1/2", "irs1/2 by", "phosphorylated stat3", "and stat5", "stat5 dimerize", "dimerize and", "and translocate", "translocate to", "the nucleus", "nucleus where", "where they", "they activate", "activate transcription", "transcription of", "jovanovic et", "2010 .", ". shp2", "shp2 activates", "activates the", "the mapk", "mapk pathway.", "pathway. irs1/2", "irs1/2 activate", "the pi3k/akt", "pi3k/akt pathway", "pathway which", "which may", "may be", "be the", "the activator", "activator of", "of mtor/s6k.
several", "mtor/s6k.
several isoforms", "isoforms of", "lepr have", "have been", "been identified", "in gorska", "gorska et", ". the", "is expressed", "expressed in", "the hypothalamus", "hypothalamus and", "and all", "all types", "types of", "of immune", "immune cells.", "cells. it", "it is", "the only", "only isoform", "isoform known", "known to", "to fully", "fully activate", "activate signaling", "pathways in", "in response", "response to", "to leptin.", "leptin. shorter", "shorter isoforms", "and a", "a soluble", "soluble isoform", "isoform lepre", "are able", "able to", "to interact", "interact with", "with jak", "jak kinases", "kinases and", "and activate", "activate other", "other pathways", "however their", "their roles", "roles in", "in energy", "energy homeostasis", "homeostasis are", "are not", "not fully", "fully characterized.", "leptin lep", "lep ob", "ob obs", "a circulating adipokine", "adipokine and", "and its receptor", "its receptor lepr", "lepr db", "db obr", "obr control", "control food intake", "food intake and", "intake and energy", "and energy balance", "energy balance and", "balance and are", "and are implicated", "are implicated in", "implicated in obesity", "in obesity related", "obesity related diseases", "diseases recently", "recently reviewed in", "reviewed in amitani", "in amitani et", "amitani et al.", "et al. 2013", "2013 dunmore", "dunmore and brown", "and brown 2013", "2013 cottrell", "cottrell and mercer", "and mercer 2012", "2012 la", "la cava 2012", "2012 marroqui", "marroqui et al.", "et al. 2012", "2012 paz", "paz filho et", "filho et al.", "2012 denver", "denver et al.", "et al. 2011", "2011 lee", "2011 marino", "marino et al.", "2011 morton", "morton and schwartz", "and schwartz 2011", "2011 scherer", "scherer and buettner", "and buettner 2011", "2011 shan", "shan and yeo", "and yeo 2011", "2011 wauman", "wauman and tavernier", "and tavernier 2011", "2011 dardeno", "dardeno et al.", "et al. 2010", "2010 bjorbaek", "2009 morris", "morris and rui", "and rui 2009", "2009 myers", "myers et al.", "et al. 2008", "cancer guo", "guo et al.", "inflammation newman", "newman and gonzalez", "and gonzalez perez", "gonzalez perez 2013", "2013 iikuni", "iikuni et al.", "angiogenesis gonzalez", "gonzalez perez et", "perez et al.", "al. 2013 .
the", "2013 .
the identification", ".
the identification of", "identification of spontaneous", "of spontaneous mutations", "spontaneous mutations in", "mutations in the", "in the leptin", "the leptin gene", "gene ob", "ob or lep", "lep and", "and the leptin", "the leptin receptor", "leptin receptor gene", "r db", "db or lepr", "lepr genes", "genes in mice", "in mice opened", "mice opened up", "opened up a", "up a new", "a new field", "new field in", "field in obesity", "in obesity research.", "obesity research. leptin", "research. leptin was", "leptin was discovered", "was discovered as", "discovered as the", "as the product", "the product of", "product of the", "of the gene", "the gene affected", "gene affected by", "affected by the", "by the ob", "ob obesity", "obesity mutation", "mutation which", "which causes obesity", "causes obesity in", "obesity in mice.", "in mice. likewise", "mice. likewise lepr", "likewise lepr is", "lepr is the", "is the product", "by the db", "db diabetic", "diabetic mutation.", "mutation. leptin binding", "leptin binding to", "binding to lepr", "to lepr induces", "lepr induces canonical", "canonical jak2/stats", "jak2/stats mapk/erk", "1/2 pi", "3k/akt and", "and non canonical", "non canonical signaling", "canonical signaling pathways", "pathways pkc", "pkc jnk", "jnk p38", "p38 mapk and", "mapk and ampk", "ampk in", "in diverse cell", "diverse cell types.", "cell types. the", "types. the binding", "the binding of", "binding of leptin", "of leptin to", "leptin to the", "to the long", "the long isoform", "long isoform of", "isoform of lepr", "lepr ob", "rl initiates", "initiates a phosphorylation", "a phosphorylation cascade", "phosphorylation cascade that", "cascade that results", "that results in", "results in transcriptional", "in transcriptional activation", "transcriptional activation of", "activation of target", "of target genes", "target genes by", "genes by stat5", "by stat5 and", "stat5 and stat3", "and stat3 and", "stat3 and activation", "and activation of", "activation of the", "of the pi3k", "the pi3k pathway", "pi3k pathway not", "pathway not shown", "not shown here", "the mapk/erk pathway", "pathway and", "and the mtor/s6k", "the mtor/s6k pathway.", "mtor/s6k pathway. shorter", "pathway. shorter lepr", "shorter lepr isoforms", "lepr isoforms with", "isoforms with truncated", "with truncated intracellular", "truncated intracellular domains", "intracellular domains are", "domains are unable", "are unable to", "unable to activate", "to activate the", "activate the stat", "the stat pathway", "pathway but", "but can transduce", "can transduce signals", "transduce signals by", "signals by way", "by way of", "way of activation", "of activation of", "activation of jak2", "jak2 irs", "irs 1 or", "1 or erks", "erks including", "including mapks.
lepr is", "mapks.
lepr is constitutively", "is constitutively bound", "constitutively bound to", "bound to the", "to the jak2", "the jak2 kinase.", "jak2 kinase. binding", "kinase. binding of", "binding of lep", "of lep to", "lep to lepr", "to lepr causes", "lepr causes a", "causes a conformational", "a conformational change", "conformational change in", "change in lepr", "in lepr that", "lepr that activates", "that activates jak2", "activates jak2 autophosphorylation", "jak2 autophosphorylation followed", "autophosphorylation followed by", "followed by phosphorylation", "by phosphorylation of", "phosphorylation of lepr", "of lepr by", "lepr by jak2.", "by jak2. phosphorylated", "jak2. phosphorylated lepr", "phosphorylated lepr binds", "lepr binds stat3", "stat3 stat5", "and shp2 which", "shp2 which are", "which are then", "are then phosphorylated", "then phosphorylated by", "phosphorylated by jak2.", "jak2. phosphorylated jak2", "phosphorylated jak2 binds", "jak2 binds sh2b1", "binds sh2b1 which", "sh2b1 which then", "which then binds", "then binds irs1/2", "irs1/2 resulting", "resulting in phosphorylation", "in phosphorylation of", "phosphorylation of irs1/2", "of irs1/2 by", "irs1/2 by jak2.", "jak2. phosphorylated stat3", "phosphorylated stat3 and", "stat3 and stat5", "and stat5 dimerize", "stat5 dimerize and", "dimerize and translocate", "and translocate to", "translocate to the", "to the nucleus", "the nucleus where", "nucleus where they", "where they activate", "they activate transcription", "activate transcription of", "transcription of target", "genes jovanovic", "jovanovic et al.", "al. 2010 .", "2010 . shp2", ". shp2 activates", "shp2 activates the", "activates the mapk", "the mapk pathway.", "mapk pathway. irs1/2", "pathway. irs1/2 activate", "irs1/2 activate the", "activate the pi3k/akt", "the pi3k/akt pathway", "pi3k/akt pathway which", "pathway which may", "which may be", "may be the", "be the activator", "the activator of", "activator of mtor/s6k.
several", "of mtor/s6k.
several isoforms", "mtor/s6k.
several isoforms of", "isoforms of lepr", "of lepr have", "lepr have been", "have been identified", "identified reviewed", "reviewed in gorska", "in gorska et", "gorska et al.", "2010 . the", ". the long", "isoform leprb", "leprb obrb", "obrb is", "is expressed in", "expressed in the", "in the hypothalamus", "the hypothalamus and", "hypothalamus and all", "and all types", "all types of", "types of immune", "of immune cells.", "immune cells. it", "cells. it is", "it is the", "is the only", "the only isoform", "only isoform known", "isoform known to", "known to fully", "to fully activate", "fully activate signaling", "activate signaling pathways", "signaling pathways in", "pathways in response", "in response to", "response to leptin.", "to leptin. shorter", "leptin. shorter isoforms", "isoforms lepra", "lepra leprc", "leprc leprd", "leprd and", "and a soluble", "a soluble isoform", "soluble isoform lepre", "lepre are", "are able to", "able to interact", "to interact with", "interact with jak", "with jak kinases", "jak kinases and", "kinases and activate", "and activate other", "activate other pathways", "pathways however", "however their roles", "their roles in", "roles in energy", "in energy homeostasis", "energy homeostasis are", "homeostasis are not", "are not fully", "not fully characterized.", "obs a", "circulating adipokine and", "adipokine and its", "and its receptor lepr", "receptor lepr db", "obr control food", "control food intake and", "food intake and energy", "intake and energy balance", "and energy balance and", "energy balance and are", "balance and are implicated", "and are implicated in", "are implicated in obesity", "implicated in obesity related", "in obesity related diseases", "related diseases recently", "diseases recently reviewed", "recently reviewed in amitani", "reviewed in amitani et", "in amitani et al.", "amitani et al. 2013", "al. 2013 dunmore", "2013 dunmore and", "dunmore and brown 2013", "brown 2013 cottrell", "2013 cottrell and", "cottrell and mercer 2012", "mercer 2012 la", "2012 la cava", "cava 2012 marroqui", "2012 marroqui et", "marroqui et al. 2012", "al. 2012 paz", "2012 paz filho", "paz filho et al.", "filho et al. 2012", "al. 2012 denver", "2012 denver et", "denver et al. 2011", "al. 2011 lee", "2011 lee 2011", "lee 2011 marino", "2011 marino et", "marino et al. 2011", "al. 2011 morton", "2011 morton and", "morton and schwartz 2011", "schwartz 2011 scherer", "2011 scherer and", "scherer and buettner 2011", "buettner 2011 shan", "2011 shan and", "shan and yeo 2011", "yeo 2011 wauman", "2011 wauman and", "wauman and tavernier 2011", "tavernier 2011 dardeno", "2011 dardeno et", "dardeno et al. 2010", "al. 2010 bjorbaek", "2010 bjorbaek 2009", "bjorbaek 2009 morris", "2009 morris and", "morris and rui 2009", "rui 2009 myers", "2009 myers et", "myers et al. 2008", "2008 including", "including cancer guo", "cancer guo et", "guo et al. 2012", "2012 inflammation", "inflammation newman and", "newman and gonzalez perez", "and gonzalez perez 2013", "perez 2013 iikuni", "2013 iikuni et", "iikuni et al. 2008", "2008 and", "and angiogenesis gonzalez", "angiogenesis gonzalez perez", "gonzalez perez et al.", "perez et al. 2013", "et al. 2013 .
the", "al. 2013 .
the identification", "2013 .
the identification of", ".
the identification of spontaneous", "identification of spontaneous mutations", "of spontaneous mutations in", "spontaneous mutations in the", "mutations in the leptin", "in the leptin gene", "leptin gene ob", "gene ob or", "or lep and", "lep and the", "and the leptin receptor", "the leptin receptor gene", "receptor gene ob", "gene ob r", "ob r db", "r db or", "or lepr genes", "lepr genes in", "genes in mice opened", "in mice opened up", "mice opened up a", "opened up a new", "up a new field", "a new field in", "new field in obesity", "field in obesity research.", "in obesity research. leptin", "obesity research. leptin was", "research. leptin was discovered", "leptin was discovered as", "was discovered as the", "discovered as the product", "as the product of", "the product of the", "product of the gene", "of the gene affected", "the gene affected by", "gene affected by the", "affected by the ob", "the ob obesity", "mutation which causes", "which causes obesity in", "causes obesity in mice.", "obesity in mice. likewise", "in mice. likewise lepr", "mice. likewise lepr is", "likewise lepr is the", "lepr is the product", "is the product of", "affected by the db", "the db diabetic", "diabetic mutation. leptin", "mutation. leptin binding to", "leptin binding to lepr", "binding to lepr induces", "to lepr induces canonical", "induces canonical jak2/stats", "jak2/stats mapk/erk 1/2", "mapk/erk 1/2 pi", "1/2 pi 3k/akt", "pi 3k/akt and", "3k/akt and non", "and non canonical signaling", "non canonical signaling pathways", "signaling pathways pkc", "jnk p38 mapk", "p38 mapk and ampk", "and ampk in", "ampk in diverse", "in diverse cell types.", "diverse cell types. the", "cell types. the binding", "types. the binding of", "the binding of leptin", "binding of leptin to", "of leptin to the", "leptin to the long", "to the long isoform", "the long isoform of", "long isoform of lepr", "of lepr ob", "lepr ob rl", "ob rl initiates", "rl initiates a", "initiates a phosphorylation cascade", "a phosphorylation cascade that", "phosphorylation cascade that results", "cascade that results in", "that results in transcriptional", "results in transcriptional activation", "in transcriptional activation of", "transcriptional activation of target", "activation of target genes", "of target genes by", "target genes by stat5", "genes by stat5 and", "by stat5 and stat3", "stat5 and stat3 and", "and stat3 and activation", "stat3 and activation of", "and activation of the", "activation of the pi3k", "of the pi3k pathway", "the pi3k pathway not", "pi3k pathway not shown", "pathway not shown here", "here the", "mapk/erk pathway and", "pathway and the", "and the mtor/s6k pathway.", "the mtor/s6k pathway. shorter", "mtor/s6k pathway. shorter lepr", "pathway. shorter lepr isoforms", "shorter lepr isoforms with", "lepr isoforms with truncated", "isoforms with truncated intracellular", "with truncated intracellular domains", "truncated intracellular domains are", "intracellular domains are unable", "domains are unable to", "are unable to activate", "unable to activate the", "to activate the stat", "activate the stat pathway", "stat pathway but", "pathway but can", "but can transduce signals", "can transduce signals by", "transduce signals by way", "signals by way of", "by way of activation", "way of activation of", "of activation of jak2", "of jak2 irs", "jak2 irs 1", "irs 1 or erks", "or erks including", "erks including mapks.
lepr", "including mapks.
lepr is constitutively", "mapks.
lepr is constitutively bound", "is constitutively bound to", "constitutively bound to the", "bound to the jak2", "to the jak2 kinase.", "the jak2 kinase. binding", "jak2 kinase. binding of", "kinase. binding of lep", "binding of lep to", "of lep to lepr", "lep to lepr causes", "to lepr causes a", "lepr causes a conformational", "causes a conformational change", "a conformational change in", "conformational change in lepr", "change in lepr that", "in lepr that activates", "lepr that activates jak2", "that activates jak2 autophosphorylation", "activates jak2 autophosphorylation followed", "jak2 autophosphorylation followed by", "autophosphorylation followed by phosphorylation", "followed by phosphorylation of", "by phosphorylation of lepr", "phosphorylation of lepr by", "of lepr by jak2.", "lepr by jak2. phosphorylated", "by jak2. phosphorylated lepr", "jak2. phosphorylated lepr binds", "phosphorylated lepr binds stat3", "binds stat3 stat5", "stat5 and shp2", "and shp2 which are", "shp2 which are then", "which are then phosphorylated", "are then phosphorylated by", "then phosphorylated by jak2.", "phosphorylated by jak2. phosphorylated", "by jak2. phosphorylated jak2", "jak2. phosphorylated jak2 binds", "phosphorylated jak2 binds sh2b1", "jak2 binds sh2b1 which", "binds sh2b1 which then", "sh2b1 which then binds", "which then binds irs1/2", "binds irs1/2 resulting", "irs1/2 resulting in", "resulting in phosphorylation of", "in phosphorylation of irs1/2", "phosphorylation of irs1/2 by", "of irs1/2 by jak2.", "irs1/2 by jak2. phosphorylated", "by jak2. phosphorylated stat3", "jak2. phosphorylated stat3 and", "phosphorylated stat3 and stat5", "stat3 and stat5 dimerize", "and stat5 dimerize and", "stat5 dimerize and translocate", "dimerize and translocate to", "and translocate to the", "translocate to the nucleus", "to the nucleus where", "the nucleus where they", "nucleus where they activate", "where they activate transcription", "they activate transcription of", "activate transcription of target", "transcription of target genes", "target genes jovanovic", "genes jovanovic et", "jovanovic et al. 2010", "et al. 2010 .", "al. 2010 . shp2", "2010 . shp2 activates", ". shp2 activates the", "shp2 activates the mapk", "activates the mapk pathway.", "the mapk pathway. irs1/2", "mapk pathway. irs1/2 activate", "pathway. irs1/2 activate the", "irs1/2 activate the pi3k/akt", "activate the pi3k/akt pathway", "the pi3k/akt pathway which", "pi3k/akt pathway which may", "pathway which may be", "which may be the", "may be the activator", "be the activator of", "the activator of mtor/s6k.
several", "activator of mtor/s6k.
several isoforms", "of mtor/s6k.
several isoforms of", "mtor/s6k.
several isoforms of lepr", "isoforms of lepr have", "of lepr have been", "lepr have been identified", "been identified reviewed", "identified reviewed in", "reviewed in gorska et", "in gorska et al.", "gorska et al. 2010", "al. 2010 . the", "2010 . the long", ". the long isoform", "long isoform leprb", "obrb is expressed", "is expressed in the", "expressed in the hypothalamus", "in the hypothalamus and", "the hypothalamus and all", "hypothalamus and all types", "and all types of", "all types of immune", "types of immune cells.", "of immune cells. it", "immune cells. it is", "cells. it is the", "it is the only", "is the only isoform", "the only isoform known", "only isoform known to", "isoform known to fully", "known to fully activate", "to fully activate signaling", "fully activate signaling pathways", "activate signaling pathways in", "signaling pathways in response", "pathways in response to", "in response to leptin.", "response to leptin. shorter", "to leptin. shorter isoforms", "shorter isoforms lepra", "leprd and a", "and a soluble isoform", "a soluble isoform lepre", "isoform lepre are", "lepre are able", "are able to interact", "able to interact with", "to interact with jak", "interact with jak kinases", "with jak kinases and", "jak kinases and activate", "kinases and activate other", "and activate other pathways", "other pathways however", "pathways however their", "however their roles in", "their roles in energy", "roles in energy homeostasis", "in energy homeostasis are", "energy homeostasis are not", "homeostasis are not fully", "are not fully characterized.", "leptin lep ob", "lep ob obs", "obs a circulating", "a circulating adipokine and", "circulating adipokine and its", "adipokine and its receptor", "its receptor lepr db", "lepr db obr", "db obr control", "obr control food intake", "control food intake and energy", "food intake and energy balance", "intake and energy balance and", "and energy balance and are", "energy balance and are implicated", "balance and are implicated in", "and are implicated in obesity", "are implicated in obesity related", "implicated in obesity related diseases", "obesity related diseases recently", "related diseases recently reviewed", "diseases recently reviewed in", "recently reviewed in amitani et", "reviewed in amitani et al.", "in amitani et al. 2013", "et al. 2013 dunmore", "al. 2013 dunmore and", "2013 dunmore and brown", "and brown 2013 cottrell", "brown 2013 cottrell and", "2013 cottrell and mercer", "and mercer 2012 la", "mercer 2012 la cava", "2012 la cava 2012", "la cava 2012 marroqui", "cava 2012 marroqui et", "2012 marroqui et al.", "et al. 2012 paz", "al. 2012 paz filho", "2012 paz filho et", "paz filho et al. 2012", "et al. 2012 denver", "al. 2012 denver et", "2012 denver et al.", "et al. 2011 lee", "al. 2011 lee 2011", "lee 2011 marino et", "2011 marino et al.", "et al. 2011 morton", "al. 2011 morton and", "2011 morton and schwartz", "and schwartz 2011 scherer", "schwartz 2011 scherer and", "2011 scherer and buettner", "and buettner 2011 shan", "buettner 2011 shan and", "2011 shan and yeo", "and yeo 2011 wauman", "yeo 2011 wauman and", "2011 wauman and tavernier", "and tavernier 2011 dardeno", "tavernier 2011 dardeno et", "2011 dardeno et al.", "et al. 2010 bjorbaek", "al. 2010 bjorbaek 2009", "bjorbaek 2009 morris and", "2009 morris and rui", "and rui 2009 myers", "rui 2009 myers et", "2009 myers et al.", "al. 2008 including", "2008 including cancer", "including cancer guo et", "cancer guo et al.", "al. 2012 inflammation", "inflammation newman and gonzalez", "newman and gonzalez perez 2013", "gonzalez perez 2013 iikuni", "perez 2013 iikuni et", "2013 iikuni et al.", "al. 2008 and", "2008 and angiogenesis", "and angiogenesis gonzalez perez", "angiogenesis gonzalez perez et", "gonzalez perez et al. 2013", "perez et al. 2013 .
the", "et al. 2013 .
the identification", "al. 2013 .
the identification of", "2013 .
the identification of spontaneous", ".
the identification of spontaneous mutations", "identification of spontaneous mutations in", "of spontaneous mutations in the", "spontaneous mutations in the leptin", "mutations in the leptin gene", "the leptin gene ob", "leptin gene ob or", "gene ob or lep", "ob or lep and", "or lep and the", "lep and the leptin", "and the leptin receptor gene", "leptin receptor gene ob", "receptor gene ob r", "ob r db or", "r db or lepr", "db or lepr genes", "or lepr genes in", "lepr genes in mice", "genes in mice opened up", "in mice opened up a", "mice opened up a new", "opened up a new field", "up a new field in", "a new field in obesity", "new field in obesity research.", "field in obesity research. leptin", "in obesity research. leptin was", "obesity research. leptin was discovered", "research. leptin was discovered as", "leptin was discovered as the", "was discovered as the product", "discovered as the product of", "as the product of the", "the product of the gene", "product of the gene affected", "of the gene affected by", "the gene affected by the", "gene affected by the ob", "by the ob obesity", "ob obesity mutation", "obesity mutation which", "mutation which causes obesity", "which causes obesity in mice.", "causes obesity in mice. likewise", "obesity in mice. likewise lepr", "in mice. likewise lepr is", "mice. likewise lepr is the", "likewise lepr is the product", "lepr is the product of", "is the product of the", "gene affected by the db", "by the db diabetic", "db diabetic mutation.", "diabetic mutation. leptin binding", "mutation. leptin binding to lepr", "leptin binding to lepr induces", "binding to lepr induces canonical", "lepr induces canonical jak2/stats", "canonical jak2/stats mapk/erk", "mapk/erk 1/2 pi 3k/akt", "pi 3k/akt and non", "3k/akt and non canonical", "and non canonical signaling pathways", "canonical signaling pathways pkc", "pathways pkc jnk", "pkc jnk p38", "jnk p38 mapk and", "mapk and ampk in", "and ampk in diverse", "ampk in diverse cell", "in diverse cell types. the", "diverse cell types. the binding", "cell types. the binding of", "types. the binding of leptin", "the binding of leptin to", "binding of leptin to the", "of leptin to the long", "leptin to the long isoform", "to the long isoform of", "the long isoform of lepr", "isoform of lepr ob", "of lepr ob rl", "ob rl initiates a", "rl initiates a phosphorylation", "initiates a phosphorylation cascade that", "a phosphorylation cascade that results", "phosphorylation cascade that results in", "cascade that results in transcriptional", "that results in transcriptional activation", "results in transcriptional activation of", "in transcriptional activation of target", "transcriptional activation of target genes", "activation of target genes by", "of target genes by stat5", "target genes by stat5 and", "genes by stat5 and stat3", "by stat5 and stat3 and", "stat5 and stat3 and activation", "and stat3 and activation of", "stat3 and activation of the", "and activation of the pi3k", "activation of the pi3k pathway", "of the pi3k pathway not", "the pi3k pathway not shown", "pi3k pathway not shown here", "shown here the", "here the mapk/erk", "the mapk/erk pathway and", "mapk/erk pathway and the", "pathway and the mtor/s6k", "and the mtor/s6k pathway. shorter", "the mtor/s6k pathway. shorter lepr", "mtor/s6k pathway. shorter lepr isoforms", "pathway. shorter lepr isoforms with", "shorter lepr isoforms with truncated", "lepr isoforms with truncated intracellular", "isoforms with truncated intracellular domains", "with truncated intracellular domains are", "truncated intracellular domains are unable", "intracellular domains are unable to", "domains are unable to activate", "are unable to activate the", "unable to activate the stat", "to activate the stat pathway", "the stat pathway but", "stat pathway but can", "pathway but can transduce", "but can transduce signals by", "can transduce signals by way", "transduce signals by way of", "signals by way of activation", "by way of activation of", "way of activation of jak2", "activation of jak2 irs", "of jak2 irs 1", "jak2 irs 1 or", "1 or erks including", "or erks including mapks.
lepr", "erks including mapks.
lepr is", "including mapks.
lepr is constitutively bound", "mapks.
lepr is constitutively bound to", "is constitutively bound to the", "constitutively bound to the jak2", "bound to the jak2 kinase.", "to the jak2 kinase. binding", "the jak2 kinase. binding of", "jak2 kinase. binding of lep", "kinase. binding of lep to", "binding of lep to lepr", "of lep to lepr causes", "lep to lepr causes a", "to lepr causes a conformational", "lepr causes a conformational change", "causes a conformational change in", "a conformational change in lepr", "conformational change in lepr that", "change in lepr that activates", "in lepr that activates jak2", "lepr that activates jak2 autophosphorylation", "that activates jak2 autophosphorylation followed", "activates jak2 autophosphorylation followed by", "jak2 autophosphorylation followed by phosphorylation", "autophosphorylation followed by phosphorylation of", "followed by phosphorylation of lepr", "by phosphorylation of lepr by", "phosphorylation of lepr by jak2.", "of lepr by jak2. phosphorylated", "lepr by jak2. phosphorylated lepr", "by jak2. phosphorylated lepr binds", "jak2. phosphorylated lepr binds stat3", "lepr binds stat3 stat5", "stat3 stat5 and", "stat5 and shp2 which", "and shp2 which are then", "shp2 which are then phosphorylated", "which are then phosphorylated by", "are then phosphorylated by jak2.", "then phosphorylated by jak2. phosphorylated", "phosphorylated by jak2. phosphorylated jak2", "by jak2. phosphorylated jak2 binds", "jak2. phosphorylated jak2 binds sh2b1", "phosphorylated jak2 binds sh2b1 which", "jak2 binds sh2b1 which then", "binds sh2b1 which then binds", "sh2b1 which then binds irs1/2", "then binds irs1/2 resulting", "binds irs1/2 resulting in", "irs1/2 resulting in phosphorylation", "resulting in phosphorylation of irs1/2", "in phosphorylation of irs1/2 by", "phosphorylation of irs1/2 by jak2.", "of irs1/2 by jak2. phosphorylated", "irs1/2 by jak2. phosphorylated stat3", "by jak2. phosphorylated stat3 and", "jak2. phosphorylated stat3 and stat5", "phosphorylated stat3 and stat5 dimerize", "stat3 and stat5 dimerize and", "and stat5 dimerize and translocate", "stat5 dimerize and translocate to", "dimerize and translocate to the", "and translocate to the nucleus", "translocate to the nucleus where", "to the nucleus where they", "the nucleus where they activate", "nucleus where they activate transcription", "where they activate transcription of", "they activate transcription of target", "activate transcription of target genes", "of target genes jovanovic", "target genes jovanovic et", "genes jovanovic et al.", "jovanovic et al. 2010 .", "et al. 2010 . shp2", "al. 2010 . shp2 activates", "2010 . shp2 activates the", ". shp2 activates the mapk", "shp2 activates the mapk pathway.", "activates the mapk pathway. irs1/2", "the mapk pathway. irs1/2 activate", "mapk pathway. irs1/2 activate the", "pathway. irs1/2 activate the pi3k/akt", "irs1/2 activate the pi3k/akt pathway", "activate the pi3k/akt pathway which", "the pi3k/akt pathway which may", "pi3k/akt pathway which may be", "pathway which may be the", "which may be the activator", "may be the activator of", "be the activator of mtor/s6k.
several", "the activator of mtor/s6k.
several isoforms", "activator of mtor/s6k.
several isoforms of", "of mtor/s6k.
several isoforms of lepr", "mtor/s6k.
several isoforms of lepr have", "isoforms of lepr have been", "of lepr have been identified", "have been identified reviewed", "been identified reviewed in", "identified reviewed in gorska", "reviewed in gorska et al.", "in gorska et al. 2010", "gorska et al. 2010 .", "et al. 2010 . the", "al. 2010 . the long", "2010 . the long isoform", "the long isoform leprb", "isoform leprb obrb", "leprb obrb is", "obrb is expressed in", "is expressed in the hypothalamus", "expressed in the hypothalamus and", "in the hypothalamus and all", "the hypothalamus and all types", "hypothalamus and all types of", "and all types of immune", "all types of immune cells.", "types of immune cells. it", "of immune cells. it is", "immune cells. it is the", "cells. it is the only", "it is the only isoform", "is the only isoform known", "the only isoform known to", "only isoform known to fully", "isoform known to fully activate", "known to fully activate signaling", "to fully activate signaling pathways", "fully activate signaling pathways in", "activate signaling pathways in response", "signaling pathways in response to", "pathways in response to leptin.", "in response to leptin. shorter", "response to leptin. shorter isoforms", "leptin. shorter isoforms lepra", "isoforms lepra leprc", "lepra leprc leprd", "leprc leprd and", "leprd and a soluble", "and a soluble isoform lepre", "soluble isoform lepre are", "isoform lepre are able", "lepre are able to", "are able to interact with", "able to interact with jak", "to interact with jak kinases", "interact with jak kinases and", "with jak kinases and activate", "jak kinases and activate other", "kinases and activate other pathways", "activate other pathways however", "other pathways however their", "pathways however their roles", "however their roles in energy", "their roles in energy homeostasis", "roles in energy homeostasis are", "in energy homeostasis are not", "energy homeostasis are not fully", "homeostasis are not fully characterized." ] }, 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transcription", "1998 .
transcription of", ".
transcription of the", "of the human", "the human insulin", "human insulin gene", "insulin gene ins", "gene ins is", "ins is annotated", "is annotated as", "annotated as part", "as part of", "part of the", "of the pathway", "the pathway \u201cregulation", "pathway \u201cregulation of", "\u201cregulation of gene", "of gene expression", "gene expression in", "expression in beta", "in beta cells\u201d", "cells\u201d see", "see reaction r", "reaction r hsa", "r hsa 211289", "hsa 211289 .", "211289 . the", ". the preproinsulin", "the preproinsulin mrna", "preproinsulin mrna is", "mrna is translated", "is translated by", "translated by ribosomes", "by ribosomes at", "ribosomes at the", "at the rough", "the rough endoplasmic", "rough endoplasmic reticulum", "er and", "and the preproinsulin", "the preproinsulin enters", "preproinsulin enters the", "enters the secretion", "the secretion pathway", "secretion pathway by", "pathway by virtue", "by virtue of", "virtue of its", "of its signal", "its signal peptide", "peptide which", "which is co", "is co translationally", "co translationally cleaved", "translationally cleaved to", "cleaved to yield", "to yield proinsulin.
in", "yield proinsulin.
in the", "proinsulin.
in the process", "the process annotated", "process annotated here", "here within", "within the er", "er three", "three intramolecular disulfide", "disulfide bonds form", "bonds form in", "form in proinsulin", "proinsulin mediated", "mediated by p4hd", "p4hd pdi1a", "pdi1a and", "and ero1b proteins.", "ero1b proteins. correctly", "proteins. correctly folded", "folded disulfide", "disulfide bonded proinsulin", "bonded proinsulin then", "proinsulin then moves", "then moves via", "moves via vesicles", "via vesicles from", "vesicles from the", "from the er", "the er to", "er to the", "to the golgi", "the golgi complex", "golgi complex where", "complex where it", "where it forms", "it forms complexes", "forms complexes with", "complexes with zinc", "with zinc and", "zinc and calcium.
proinsulin", "and calcium.
proinsulin zinc", "calcium.
proinsulin zinc calcium", "calcium complexes bud", "complexes bud in", "bud in vesicles", "in vesicles from", "from the trans", "the trans golgi", "trans golgi to", "golgi to form", "to form immature", "form immature secretory", "immature secretory vesicles", "vesicles secretory", "granules in", "in the cytosol.", "the cytosol. within", "cytosol. within the", "within the immature", "the immature granules", "granules endoproteases", "endoproteases pcks1 and", "pcks1 and pcks2", "pcks2 prohormone", "prohormone convertases 1", "convertases 1 and", "1 and 2", "2 cleave", "cleave proinsulin at", "proinsulin at two", "at two sites", "two sites and", "sites and cpe", "cpe carboxypeptidase", "e removes", "removes additional amino", "additional amino acid", "amino acid residues", "acid residues to", "residues to yield", "to yield the", "yield the cystine", "the cystine bonded", "cystine bonded a", "bonded a and", "a and b", "and b chains", "b chains of", "chains of mature", "of mature insulin", "mature insulin and", "insulin and the", "and the c", "the c peptide", "which will be", "will be secreted", "be secreted with", "secreted with the", "with the insulin.", "the insulin. the", "insulin. the insulin", "the insulin zinc", "insulin zinc calcium", "calcium complexes form", "complexes form insoluble", "form insoluble crystals", "insoluble crystals within", "crystals within the", "within the granule.
the", "the granule.
the insulin", "granule.
the insulin containing", "secretory granules are", "granules are then", "are then translocated", "then translocated across", "translocated across the", "to the inner", "the inner surface", "inner surface of", "surface of the", "of the plasma", "the plasma membrane.", "plasma membrane. translocation", "membrane. translocation occurs", "translocation occurs initially", "occurs initially by", "initially by attachment", "by attachment of", "attachment of the", "the granules to", "granules to kinesin", "to kinesin 1", "1 which", "which motors along", "motors along microtubules", "microtubules and", "and then by", "then by attachment", "by attachment to", "attachment to myosin", "to myosin va", "va which", "motors along the", "along the microfilaments", "the microfilaments of", "microfilaments of the", "of the cortical", "the cortical actin", "cortical actin network.
a", "actin network.
a pancreatic", "network.
a pancreatic beta", "pancreatic beta cell", "beta cell contains", "cell contains about", "contains about 10", "about 10 000", "10 000 insulin", "000 insulin granules", "insulin granules of", "granules of which", "of which about", "which about 1", "about 1 000", "1 000 are", "000 are docked", "are docked at", "docked at the", "at the plasma", "plasma membrane and", "membrane and 50", "and 50 are", "50 are readily", "are readily releasable", "readily releasable in", "releasable in immediate", "in immediate response", "immediate response to", "response to stimulation", "to stimulation by", "stimulation by glucose", "by glucose or", "glucose or other", "or other secretogogues.", "other secretogogues. docking", "secretogogues. docking is", "docking is due", "is due to", "due to interaction", "to interaction between", "interaction between the", "between the exocyst", "the exocyst proteins", "exocyst proteins exoc3", "proteins exoc3 on", "exoc3 on the", "on the granule", "the granule membrane", "granule membrane and", "membrane and exoc4", "and exoc4 on", "exoc4 on the", "on the plasma", "plasma membrane. exocytosis", "membrane. exocytosis is", "exocytosis is accomplished", "is accomplished by", "accomplished by interaction", "by interaction between", "interaction between snare", "between snare type", "snare type proteins", "type proteins syntaxin", "proteins syntaxin 1a", "syntaxin 1a and", "1a and syntaxin", "and syntaxin 4", "syntaxin 4 on", "4 on the", "membrane and synaptobrevin", "and synaptobrevin 2/vamp2", "synaptobrevin 2/vamp2 on", "2/vamp2 on the", "the granule membrane.", "granule membrane. exocytosis", "exocytosis is a", "is a calcium", "a calcium dependent", "calcium dependent process", "dependent process due", "process due to", "to interaction of", "interaction of the", "of the calcium", "the calcium binding", "calcium binding membrane", "binding membrane protein", "membrane protein synaptotagmin", "protein synaptotagmin v/ix", "synaptotagmin v/ix with", "v/ix with the", "with the snare", "the snare type", "snare type proteins.", "generation of insulin containing", "of insulin containing secretory", "insulin containing secretory granules", "containing secretory granules from", "secretory granules from newly", "granules from newly synthesized", "from newly synthesized proinsulin", "newly synthesized proinsulin in", "synthesized proinsulin in the", "proinsulin in the lumen", "in the lumen of", "the lumen of the", "lumen of the endoplasmic", "of the endoplasmic reticulum", "endoplasmic reticulum er", "er involves formation", "involves formation of proinsulin", "formation of proinsulin intramolecular", "of proinsulin intramolecular disulfide", "proinsulin intramolecular disulfide bonds", "disulfide bonds formation", "bonds formation of", "formation of proinsulin zinc", "of proinsulin zinc calcium", "proinsulin zinc calcium complexes", "calcium complexes proteolytic", "complexes proteolytic cleavage", "proteolytic cleavage of proinsulin", "cleavage of proinsulin to", "of proinsulin to yield", "proinsulin to yield insulin", "to yield insulin and", "yield insulin and c", "insulin and c peptide", "c peptide and", "peptide and translocation", "and translocation of the", "translocation of the granules", "of the granules across", "the granules across the", "granules across the cytosol", "across the cytosol to", "the cytosol to the", "cytosol to the plasma", "to the plasma membrane", "plasma membrane dodson", "membrane dodson &", "dodson & steiner 1998", "& steiner 1998 .
transcription", "steiner 1998 .
transcription of", "1998 .
transcription of the", ".
transcription of the human", "of the human insulin", "the human insulin gene", "human insulin gene ins", "insulin gene ins is", "gene ins is annotated", "ins is annotated as", "is annotated as part", "annotated as part of", "as part of the", "part of the pathway", "of the pathway \u201cregulation", "the pathway \u201cregulation of", "pathway \u201cregulation of gene", "\u201cregulation of gene expression", "of gene expression in", "gene expression in beta", "expression in beta cells\u201d", "beta cells\u201d see", "cells\u201d see reaction", "see reaction r hsa", "reaction r hsa 211289", "r hsa 211289 .", "hsa 211289 . the", "211289 . the preproinsulin", ". the preproinsulin mrna", "the preproinsulin mrna is", "preproinsulin mrna is translated", "mrna is translated by", "is translated by ribosomes", "translated by ribosomes at", "by ribosomes at the", "ribosomes at the rough", "at the rough endoplasmic", "the rough endoplasmic reticulum", "er and the", "and the preproinsulin enters", "the preproinsulin enters the", "preproinsulin enters the secretion", "enters the secretion pathway", "the secretion pathway by", "secretion pathway by virtue", "pathway by virtue of", "by virtue of its", "virtue of its signal", "of its signal peptide", "signal peptide which", "peptide which is", "which is co translationally", "is co translationally cleaved", "co translationally cleaved to", "translationally cleaved to yield", "cleaved to yield proinsulin.
in", "to yield proinsulin.
in the", "yield proinsulin.
in the process", "proinsulin.
in the process annotated", "the process annotated here", "annotated here within", "here within the", "the er three", "er three intramolecular", "three intramolecular disulfide bonds", "intramolecular disulfide bonds form", "disulfide bonds form in", "bonds form in proinsulin", "in proinsulin mediated", "proinsulin mediated by", "by p4hd pdi1a", "pdi1a and ero1b", "and ero1b proteins. correctly", "ero1b proteins. correctly folded", "correctly folded disulfide", "folded disulfide bonded", "disulfide bonded proinsulin then", "bonded proinsulin then moves", "proinsulin then moves via", "then moves via vesicles", "moves via vesicles from", "via vesicles from the", "vesicles from the er", "from the er to", "the er to the", "er to the golgi", "to the golgi complex", "the golgi complex where", "golgi complex where it", "complex where it forms", "where it forms complexes", "it forms complexes with", "forms complexes with zinc", "complexes with zinc and", "with zinc and calcium.
proinsulin", "zinc and calcium.
proinsulin zinc", "and calcium.
proinsulin zinc calcium", "calcium.
proinsulin zinc calcium complexes", "zinc calcium complexes bud", "calcium complexes bud in", "complexes bud in vesicles", "bud in vesicles from", "in vesicles from the", "vesicles from the trans", "from the trans golgi", "the trans golgi to", "trans golgi to form", "golgi to form immature", "to form immature secretory", "form immature secretory vesicles", "secretory vesicles secretory", "vesicles secretory granules", "secretory granules in", "granules in the", "in the cytosol. within", "the cytosol. within the", "cytosol. within the immature", "within the immature granules", "immature granules endoproteases", "granules endoproteases pcks1", "endoproteases pcks1 and pcks2", "and pcks2 prohormone", "pcks2 prohormone convertases", "prohormone convertases 1 and", "convertases 1 and 2", "and 2 cleave", "2 cleave proinsulin", "cleave proinsulin at two", "proinsulin at two sites", "at two sites and", "two sites and cpe", "and cpe carboxypeptidase", "cpe carboxypeptidase e", "carboxypeptidase e removes", "e removes additional", "removes additional amino acid", "additional amino acid residues", "amino acid residues to", "acid residues to yield", "residues to yield the", "to yield the cystine", "yield the cystine bonded", "the cystine bonded a", "cystine bonded a and", "bonded a and b", "a and b chains", "and b chains of", "b chains of mature", "chains of mature insulin", "of mature insulin and", "mature insulin and the", "insulin and the c", "and the c peptide", "c peptide which", "peptide which will", "which will be secreted", "will be secreted with", "be secreted with the", "secreted with the insulin.", "with the insulin. the", "the insulin. the insulin", "insulin. the insulin zinc", "the insulin zinc calcium", "insulin zinc calcium complexes", "zinc calcium complexes form", "calcium complexes form insoluble", "complexes form insoluble crystals", "form insoluble crystals within", "insoluble crystals within the", "crystals within the granule.
the", "within the granule.
the insulin", "the granule.
the insulin containing", "granule.
the insulin containing secretory", "containing secretory granules are", "secretory granules are then", "granules are then translocated", "are then translocated across", "then translocated across the", "translocated across the cytosol", "cytosol to the inner", "to the inner surface", "the inner surface of", "inner surface of the", "surface of the plasma", "of the plasma membrane.", "the plasma membrane. translocation", "plasma membrane. translocation occurs", "membrane. translocation occurs initially", "translocation occurs initially by", "occurs initially by attachment", "initially by attachment of", "by attachment of the", "attachment of the granules", "of the granules to", "the granules to kinesin", "granules to kinesin 1", "kinesin 1 which", "1 which motors", "which motors along microtubules", "along microtubules and", "microtubules and then", "and then by attachment", "then by attachment to", "by attachment to myosin", "attachment to myosin va", "myosin va which", "va which motors", "which motors along the", "motors along the microfilaments", "along the microfilaments of", "the microfilaments of the", "microfilaments of the cortical", "of the cortical actin", "the cortical actin network.
a", "cortical actin network.
a pancreatic", "actin network.
a pancreatic beta", "network.
a pancreatic beta cell", "pancreatic beta cell contains", "beta cell contains about", "cell contains about 10", "contains about 10 000", "about 10 000 insulin", "10 000 insulin granules", "000 insulin granules of", "insulin granules of which", "granules of which about", "of which about 1", "which about 1 000", "about 1 000 are", "1 000 are docked", "000 are docked at", "are docked at the", "docked at the plasma", "at the plasma membrane", "the plasma membrane and", "plasma membrane and 50", "membrane and 50 are", "and 50 are readily", "50 are readily releasable", "are readily releasable in", "readily releasable in immediate", "releasable in immediate response", "in immediate response to", "immediate response to stimulation", "response to stimulation by", "to stimulation by glucose", "stimulation by glucose or", "by glucose or other", "glucose or other secretogogues.", "or other secretogogues. docking", "other secretogogues. docking is", "secretogogues. docking is due", "docking is due to", "is due to interaction", "due to interaction between", "to interaction between the", "interaction between the exocyst", "between the exocyst proteins", "the exocyst proteins exoc3", "exocyst proteins exoc3 on", "proteins exoc3 on the", "exoc3 on the granule", "on the granule membrane", "the granule membrane and", "granule membrane and exoc4", "membrane and exoc4 on", "and exoc4 on the", "exoc4 on the plasma", "on the plasma membrane.", "the plasma membrane. exocytosis", "plasma membrane. exocytosis is", "membrane. exocytosis is accomplished", "exocytosis is accomplished by", "is accomplished by interaction", "accomplished by interaction between", "by interaction between snare", "interaction between snare type", "between snare type proteins", "snare type proteins syntaxin", "type proteins syntaxin 1a", "proteins syntaxin 1a and", "syntaxin 1a and syntaxin", "1a and syntaxin 4", "and syntaxin 4 on", "syntaxin 4 on the", "4 on the plasma", "on the plasma membrane", "plasma membrane and synaptobrevin", "membrane and synaptobrevin 2/vamp2", "and synaptobrevin 2/vamp2 on", "synaptobrevin 2/vamp2 on the", "2/vamp2 on the granule", "on the granule membrane.", "the granule membrane. exocytosis", "granule membrane. exocytosis is", "membrane. exocytosis is a", "exocytosis is a calcium", "is a calcium dependent", "a calcium dependent process", "calcium dependent process due", "dependent process due to", "process due to interaction", "due to interaction of", "to interaction of the", "interaction of the calcium", "of the calcium binding", "the calcium binding membrane", "calcium binding membrane protein", "binding membrane protein synaptotagmin", "membrane protein synaptotagmin v/ix", "protein synaptotagmin v/ix with", "synaptotagmin v/ix with the", "v/ix with the snare", "with the snare type", "the snare type proteins.", "generation of insulin containing secretory", "of insulin containing secretory granules", "insulin containing secretory granules from", "containing secretory granules from newly", "secretory granules from newly synthesized", "granules from newly synthesized proinsulin", "from newly synthesized proinsulin in", "newly synthesized proinsulin in the", "synthesized proinsulin in the lumen", "proinsulin in the lumen of", "in the lumen of the", "the lumen of the endoplasmic", "lumen of the endoplasmic reticulum", "the endoplasmic reticulum er", "reticulum er involves", "er involves formation of", "involves formation of proinsulin intramolecular", "formation of proinsulin intramolecular disulfide", "of proinsulin intramolecular disulfide bonds", "intramolecular disulfide bonds formation", "disulfide bonds formation of", "bonds formation of proinsulin", "formation of proinsulin zinc calcium", "of proinsulin zinc calcium complexes", "zinc calcium complexes proteolytic", "calcium complexes proteolytic cleavage", "complexes proteolytic cleavage of", "proteolytic cleavage of proinsulin to", "cleavage of proinsulin to yield", "of proinsulin to yield insulin", "proinsulin to yield insulin and", "to yield insulin and c", "yield insulin and c peptide", "and c peptide and", "c peptide and translocation", "peptide and translocation of", "and translocation of the granules", "translocation of the granules across", "of the granules across the", "the granules across the cytosol", "granules across the cytosol to", "across the cytosol to the", "the cytosol to the plasma", "cytosol to the plasma membrane", "the plasma membrane dodson", "plasma membrane dodson &", "membrane dodson & steiner", "dodson & steiner 1998 .
transcription", "& steiner 1998 .
transcription of", "steiner 1998 .
transcription of the", "1998 .
transcription of the human", ".
transcription of the human insulin", "of the human insulin gene", "the human insulin gene ins", "human insulin gene ins is", "insulin gene ins is annotated", "gene ins is annotated as", "ins is annotated as part", "is annotated as part of", "annotated as part of the", "as part of the pathway", "part of the pathway \u201cregulation", "of the pathway \u201cregulation of", "the pathway \u201cregulation of gene", "pathway \u201cregulation of gene expression", "\u201cregulation of gene expression in", "of gene expression in beta", "gene expression in beta cells\u201d", "in beta cells\u201d see", "beta cells\u201d see reaction", "cells\u201d see reaction r", "see reaction r hsa 211289", "reaction r hsa 211289 .", "r hsa 211289 . the", "hsa 211289 . the preproinsulin", "211289 . the preproinsulin mrna", ". the preproinsulin mrna is", "the preproinsulin mrna is translated", "preproinsulin mrna is translated by", "mrna is translated by ribosomes", "is translated by ribosomes at", "translated by ribosomes at the", "by ribosomes at the rough", "ribosomes at the rough endoplasmic", "at the rough endoplasmic reticulum", "rough endoplasmic reticulum er", "reticulum er and", "er and the preproinsulin", "and the preproinsulin enters the", "the preproinsulin enters the secretion", "preproinsulin enters the secretion pathway", "enters the secretion pathway by", "the secretion pathway by virtue", "secretion pathway by virtue of", "pathway by virtue of its", "by virtue of its signal", "virtue of its signal peptide", "its signal peptide which", "signal peptide which is", "peptide which is co", "which is co translationally cleaved", "is co translationally cleaved to", "co translationally cleaved to yield", "translationally cleaved to yield proinsulin.
in", "cleaved to yield proinsulin.
in the", "to yield proinsulin.
in the process", "yield proinsulin.
in the process annotated", "proinsulin.
in the process annotated here", "process annotated here within", "annotated here within the", "here within the er", "within the er three", "the er three intramolecular", "er three intramolecular disulfide", "three intramolecular disulfide bonds form", "intramolecular disulfide bonds form in", "disulfide bonds form in proinsulin", "form in proinsulin mediated", "in proinsulin mediated by", "proinsulin mediated by p4hd", "mediated by p4hd pdi1a", "p4hd pdi1a and", "pdi1a and ero1b proteins.", "and ero1b proteins. correctly folded", "proteins. correctly folded disulfide", "correctly folded disulfide bonded", "folded disulfide bonded proinsulin", "disulfide bonded proinsulin then moves", "bonded proinsulin then moves via", "proinsulin then moves via vesicles", "then moves via vesicles from", "moves via vesicles from the", "via vesicles from the er", "vesicles from the er to", "from the er to the", "the er to the golgi", "er to the golgi complex", "to the golgi complex where", "the golgi complex where it", "golgi complex where it forms", "complex where it forms complexes", "where it forms complexes with", "it forms complexes with zinc", "forms complexes with zinc and", "complexes with zinc and calcium.
proinsulin", "with zinc and calcium.
proinsulin zinc", "zinc and calcium.
proinsulin zinc calcium", "and calcium.
proinsulin zinc calcium complexes", "calcium.
proinsulin zinc calcium complexes bud", "zinc calcium complexes bud in", "calcium complexes bud in vesicles", "complexes bud in vesicles from", "bud in vesicles from the", "in vesicles from the trans", "vesicles from the trans golgi", "from the trans golgi to", "the trans golgi to form", "trans golgi to form immature", "golgi to form immature secretory", "to form immature secretory vesicles", "immature secretory vesicles secretory", "secretory vesicles secretory granules", "secretory granules in the", "granules in the cytosol.", "in the cytosol. within the", "the cytosol. within the immature", "cytosol. within the immature granules", "the immature granules endoproteases", "immature granules endoproteases pcks1", "granules endoproteases pcks1 and", "pcks1 and pcks2 prohormone", "and pcks2 prohormone convertases", "pcks2 prohormone convertases 1", "prohormone convertases 1 and 2", "1 and 2 cleave", "and 2 cleave proinsulin", "2 cleave proinsulin at", "cleave proinsulin at two sites", "proinsulin at two sites and", "at two sites and cpe", "sites and cpe carboxypeptidase", "and cpe carboxypeptidase e", "carboxypeptidase e removes additional", "e removes additional amino", "removes additional amino acid residues", "additional amino acid residues to", "amino acid residues to yield", "acid residues to yield the", "residues to yield the cystine", "to yield the cystine bonded", "yield the cystine bonded a", "the cystine bonded a and", "cystine bonded a and b", "bonded a and b chains", "a and b chains of", "and b chains of mature", "b chains of mature insulin", "chains of mature insulin and", "of mature insulin and the", "mature insulin and the c", "insulin and the c peptide", "the c peptide which", "c peptide which will", "peptide which will be", "which will be secreted with", "will be secreted with the", "be secreted with the insulin.", "secreted with the insulin. the", "with the insulin. the insulin", "the insulin. the insulin zinc", "insulin. the insulin zinc calcium", "the insulin zinc calcium complexes", "insulin zinc calcium complexes form", "zinc calcium complexes form insoluble", "calcium complexes form insoluble crystals", "complexes form insoluble crystals within", "form insoluble crystals within the", "insoluble crystals within the granule.
the", "crystals within the granule.
the insulin", "within the granule.
the insulin containing", "the granule.
the insulin containing secretory", "granule.
the insulin containing secretory granules", "insulin containing secretory granules are", "containing secretory granules are then", "secretory granules are then translocated", "granules are then translocated across", "are then translocated across the", "then translocated across the cytosol", "translocated across the cytosol to", "the cytosol to the inner", "cytosol to the inner surface", "to the inner surface of", "the inner surface of the", "inner surface of the plasma", "surface of the plasma membrane.", "of the plasma membrane. translocation", "the plasma membrane. translocation occurs", "plasma membrane. translocation occurs initially", "membrane. translocation occurs initially by", "translocation occurs initially by attachment", "occurs initially by attachment of", "initially by attachment of the", "by attachment of the granules", "attachment of the granules to", "of the granules to kinesin", "the granules to kinesin 1", "to kinesin 1 which", "kinesin 1 which motors", "1 which motors along", "motors along microtubules and", "along microtubules and then", "microtubules and then by", "and then by attachment to", "then by attachment to myosin", "by attachment to myosin va", "to myosin va which", "myosin va which motors", "va which motors along", "which motors along the microfilaments", "motors along the microfilaments of", "along the microfilaments of the", "the microfilaments of the cortical", "microfilaments of the cortical actin", "of the cortical actin network.
a", "the cortical actin network.
a pancreatic", "cortical actin network.
a pancreatic beta", "actin network.
a pancreatic beta cell", "network.
a pancreatic beta cell contains", "pancreatic beta cell contains about", "beta cell contains about 10", "cell contains about 10 000", "contains about 10 000 insulin", "about 10 000 insulin granules", "10 000 insulin granules of", "000 insulin granules of which", "insulin granules of which about", "granules of which about 1", "of which about 1 000", "which about 1 000 are", "about 1 000 are docked", "1 000 are docked at", "000 are docked at the", "are docked at the plasma", "docked at the plasma membrane", "at the plasma membrane and", "the plasma membrane and 50", "plasma membrane and 50 are", "membrane and 50 are readily", "and 50 are readily releasable", "50 are readily releasable in", "are readily releasable in immediate", "readily releasable in immediate response", "releasable in immediate response to", "in immediate response to stimulation", "immediate response to stimulation by", "response to stimulation by glucose", "to stimulation by glucose or", "stimulation by glucose or other", "by glucose or other secretogogues.", "glucose or other secretogogues. docking", "or other secretogogues. docking is", "other secretogogues. docking is due", "secretogogues. docking is due to", "docking is due to interaction", "is due to interaction between", "due to interaction between the", "to interaction between the exocyst", "interaction between the exocyst proteins", "between the exocyst proteins exoc3", "the exocyst proteins exoc3 on", "exocyst proteins exoc3 on the", "proteins exoc3 on the granule", "exoc3 on the granule membrane", "on the granule membrane and", "the granule membrane and exoc4", "granule membrane and exoc4 on", "membrane and exoc4 on the", "and exoc4 on the plasma", "exoc4 on the plasma membrane.", "on the plasma membrane. exocytosis", "the plasma membrane. exocytosis is", "plasma membrane. exocytosis is accomplished", "membrane. exocytosis is accomplished by", "exocytosis is accomplished by interaction", "is accomplished by interaction between", "accomplished by interaction between snare", "by interaction between snare type", "interaction between snare type proteins", "between snare type proteins syntaxin", "snare type proteins syntaxin 1a", "type proteins syntaxin 1a and", "proteins syntaxin 1a and syntaxin", "syntaxin 1a and syntaxin 4", "1a and syntaxin 4 on", "and syntaxin 4 on the", "syntaxin 4 on the plasma", "4 on the plasma membrane", "on the plasma membrane and", "the plasma membrane and synaptobrevin", "plasma membrane and synaptobrevin 2/vamp2", "membrane and synaptobrevin 2/vamp2 on", "and synaptobrevin 2/vamp2 on the", "synaptobrevin 2/vamp2 on the granule", "2/vamp2 on the granule membrane.", "on the granule membrane. exocytosis", "the granule membrane. exocytosis is", "granule membrane. exocytosis is a", "membrane. exocytosis is a calcium", "exocytosis is a calcium dependent", "is a calcium dependent process", "a calcium dependent process due", "calcium dependent process due to", "dependent process due to interaction", "process due to interaction of", "due to interaction of the", "to interaction of the calcium", "interaction of the calcium binding", "of the calcium binding membrane", "the calcium binding membrane protein", "calcium binding membrane protein synaptotagmin", "binding membrane protein synaptotagmin v/ix", "membrane protein synaptotagmin v/ix with", "protein synaptotagmin v/ix with the", "synaptotagmin v/ix with the snare", "v/ix with the snare type", "with the snare type proteins." ] }, { "record_id": "GLY_000594_1_246", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2660826", "r hsa", "hsa 2660826", "r hsa 2660826" ] }, { "record_id": "GLY_000594_1_246", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "constitutive signaling", "signaling by", "by notch1", "notch1 t", "t 7", "7 9", "translocation mutant", "constitutive signaling by", "signaling by notch1", "by notch1 t", "notch1 t 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kunzelmann et al.", "et al. 2009 hartzell", "al. 2009 hartzell et", "2009 hartzell et al.", "et al. 2008 and", "2008 and ryanodine", "and ryanodine receptor tetramers", "ryanodine receptor tetramers ryrs", "ryrs beard et", "beard et al. 2009 ." ] }, { "record_id": "GLY_000594_1_248", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2682334", "r hsa", "hsa 2682334", "r hsa 2682334" ] }, { "record_id": "GLY_000594_1_248", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "eph ephrin", "ephrin signaling", "eph ephrin signaling", "during the", "the development", "development process", "process cell", "cell migration", "migration and", "and adhesion", "adhesion are", "are the", "the main", "main forces", "forces involved", "involved in", "in morphing", "morphing the", "the cells", "cells into", "into critical", "critical anatomical", "anatomical structures.", "structures. the", "the ability", "ability 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maturation", "maturation dalva", "dalva et al.", "et al. 2007", "al. 2007 .", "2007 . on", ". on the", "on the other", "the other hand", "hand epha4", "epha4 activation leads", "activation leads to", "leads to dendritic", "to dendritic spine", "dendritic spine elimination", "elimination murai", "murai et al.", "et al. 2003", "2003 fu", "fu et al.", "al. 2007 .
eph", "2007 .
eph receptors", ".
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structures. the ability", "structures. the ability of", "the ability of a", "ability of a cell", "of a cell to", "a cell to migrate", "cell to migrate to", "to migrate to its", "migrate to its correct", "to its correct destination", "its correct destination depends", "correct destination depends heavily", "destination depends heavily on", "depends heavily on signaling", "heavily on signaling at", "on signaling at the", "signaling at the cell", "at the cell membrane.", "the cell membrane. erythropoietin", "cell membrane. erythropoietin producing", "membrane. erythropoietin producing hepatocellular", "erythropoietin producing hepatocellular carcinoma", "hepatocellular carcinoma eph", "receptors and their ligands", "their ligands the", "ligands the ephrins", "the ephrins eph", "ephrins eph receptors", "eph receptors interacting proteins", "interacting proteins efns", "efns orchestrates", "orchestrates the precise control", "the precise control necessary", "precise control necessary to", 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induces the rapid", "induces the rapid formation", "the rapid formation and", "rapid formation and enlargement", "formation and enlargement of", "and enlargement of dendritic", "enlargement of dendritic spines", "dendritic spines as", "spines as well", "as well as rapid", "well as rapid synapse", "as rapid synapse maturation", "synapse maturation dalva", "maturation dalva et", "dalva et al. 2007", "et al. 2007 .", "al. 2007 . on", "2007 . on the", ". on the other", "on the other hand", "other hand epha4", "hand epha4 activation", "epha4 activation leads to", "activation leads to dendritic", "leads to dendritic spine", "to dendritic spine elimination", "spine elimination murai", "elimination murai et", "murai et al. 2003", "al. 2003 fu", "2003 fu et", "fu et al. 2007", "et al. 2007 .
eph", "al. 2007 .
eph receptors", "2007 .
eph receptors are", ".
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signaling", "intracellular cytoplasmic signaling structure", "cytoplasmic signaling structure containing", "signaling structure containing a", "structure containing a canonical", "containing a canonical tyrosine", "a canonical tyrosine kinase", "canonical tyrosine kinase catalytic", "tyrosine kinase catalytic domain", "kinase catalytic domain as", "catalytic domain as well", "domain as well as", "as well as other", "well as other protein", "as other protein interaction", "other protein interaction sites.", "protein interaction sites. ephrins", "interaction sites. ephrins are", "sites. ephrins are also", "ephrins are also sub", "are also sub divided", "also sub divided into", "sub divided into an", "divided into an a", "into an a subclass", "a subclass a1", "subclass a1 a5", "a5 which", "which are tethered to", "are tethered to the", "tethered to the plasma", "to the plasma membrane", "the plasma membrane by", "plasma membrane by a", "membrane by a glycosylphosphatidylinositol", "a 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"interaction since both molecules", "since both molecules are", "both molecules are membrane", "molecules are membrane bound.", "are membrane bound. close", "membrane bound. close contact", "bound. close contact between", "close contact between eph", "contact between eph receptors", "receptors and efns is", "and efns is required", "efns is required for", "is required for signaling", "required for signaling to", "for signaling to occur.", "signaling to occur. eph/efn", "to occur. eph/efn initiated", "occur. eph/efn initiated signaling", "eph/efn initiated signaling occurs", "initiated signaling occurs bi", "signaling occurs bi directionally", "occurs bi directionally into", "bi directionally into either", "directionally into either eph", "either eph or", "eph or efn", "or efn expressing cells", "efn expressing cells or", "expressing cells or axons.", "cells or axons. signaling", "or axons. signaling into", "axons. signaling into the", "signaling into the eph", "into the eph receptor", "the eph receptor expressing", "eph receptor expressing cell", "receptor expressing cell is", "expressing cell is referred", "cell is referred as", "is referred as the", "referred as the forward", "as the forward signal", "the forward signal and", "forward signal and signaling", "signal and signaling into", "and signaling into the", "signaling into the efn", "into the efn expressing", "the efn expressing cell", "expressing cell the", "cell the reverse", "reverse signal. dalva", "signal. dalva et", "dalva et al. 2000", "al. 2000 grunwald", "2000 grunwald et", "grunwald et al. 2004", "al. 2004 davy", "2004 davy &", "davy & robbins 2000", "robbins 2000 cowan", "2000 cowan et", "cowan et al. 2004", "during the development process cell", "the development process cell migration", "development process cell migration and", "process cell migration and adhesion", "cell migration and adhesion are", "migration and adhesion are the", "and adhesion are the main", "adhesion are the main forces", "are the main forces involved", "the main forces involved in", "main forces involved in morphing", "forces involved in morphing the", "involved in morphing the cells", "in morphing the cells into", "morphing the cells into critical", "the cells into critical anatomical", "cells into critical anatomical structures.", "into critical anatomical structures. the", "critical anatomical structures. the ability", "anatomical structures. the ability of", "structures. the ability of a", "the ability of a cell", "ability of a cell to", "of a cell to migrate", "a cell to migrate to", "cell to migrate to its", "to migrate to its correct", "migrate to its correct destination", "to its correct destination depends", "its correct destination depends heavily", "correct destination depends heavily on", "destination depends heavily on signaling", "depends heavily on signaling at", "heavily on signaling at the", "on signaling at the cell", "signaling at the cell membrane.", "at the cell membrane. erythropoietin", "the cell membrane. erythropoietin producing", "cell membrane. erythropoietin producing hepatocellular", "membrane. erythropoietin producing hepatocellular carcinoma", "producing hepatocellular carcinoma eph", "carcinoma eph receptors", "eph receptors and their", "and their ligands the", "their ligands the ephrins", "the ephrins eph receptors", "ephrins eph receptors interacting", "receptors interacting proteins efns", "efns orchestrates the", "orchestrates the precise control necessary", "the precise control necessary to", "precise control necessary to guide", "control necessary to guide a", "necessary to guide a cell", "to guide a cell to", "guide a cell to its", "a cell to its destination.", "cell to its destination. they", "to its destination. they are", "its destination. they are expressed", "destination. they are expressed in", "they are expressed in all", "are expressed in all tissues", "expressed in all tissues of", "in all tissues of a", "all tissues of a developing", "tissues of a developing embryo", "of a developing embryo and", "a developing embryo and are", "developing embryo and are involved", "embryo and are involved in", "and are involved in multiple", "are involved in multiple developmental", "involved in multiple developmental processes", "in multiple developmental processes such", "multiple developmental processes such as", "developmental processes such as axon", "processes such as axon guidance", "as axon guidance cardiovascular", "axon guidance cardiovascular and", "guidance cardiovascular and skeletal", "cardiovascular and skeletal development and", "and skeletal development and tissue", "skeletal development and tissue patterning.", "development and tissue patterning. in", "and tissue patterning. in addition", "patterning. in addition eph", "in addition eph receptors", "addition eph receptors and", "eph receptors and efns are", "receptors and efns are expressed", "and efns are expressed in", "efns are expressed in developing", "are expressed in developing and", "expressed in developing and mature", "in developing and mature synapses", "developing and mature synapses in", "and mature synapses in the", "mature synapses in the nervous", "synapses in the nervous system", "the nervous system where", "nervous system where they", "system where they may", "where they may have a", "they may have a role", "may have a role in", "have a role in regulating", "a role in regulating synaptic", "role in regulating synaptic plasticity", "in regulating synaptic plasticity and", "regulating synaptic plasticity and long", "synaptic plasticity and long term", "plasticity and long term potentiation.", "and long term potentiation. activation", "long term potentiation. activation of", "term potentiation. activation of ephb", "potentiation. activation of ephb receptors", "activation of ephb receptors in", "of ephb receptors in neurons", "ephb receptors in neurons induces", "receptors in neurons induces the", "in neurons induces the rapid", "neurons induces the rapid formation", "induces the rapid formation and", "the rapid formation and enlargement", "rapid formation and enlargement of", "formation and enlargement of dendritic", "and enlargement of dendritic spines", "of dendritic spines as", "dendritic spines as well", "spines as well as", "as well as rapid synapse", "well as rapid synapse maturation", "rapid synapse maturation dalva", "synapse maturation dalva et", "maturation dalva et al.", "dalva et al. 2007 .", "et al. 2007 . on", "al. 2007 . on the", "2007 . on the other", ". on the other hand", "the other hand epha4", "other hand epha4 activation", "hand epha4 activation leads", "epha4 activation leads to dendritic", "activation leads to dendritic spine", "leads to dendritic spine elimination", "dendritic spine elimination murai", "spine elimination murai et", "elimination murai et al.", "et al. 2003 fu", "al. 2003 fu et", "2003 fu et al.", "fu et al. 2007 .
eph", "et al. 2007 .
eph receptors", "al. 2007 .
eph receptors are", "2007 .
eph receptors are the", ".
eph receptors are the largest", "receptors are the largest known", "are the largest known family", "the largest known family of", "largest known family of receptor", "known family of receptor tyrosine", "family of receptor tyrosine kinases", "receptor tyrosine kinases rtks", "rtks with fourteen", "with fourteen total receptors divided", "fourteen total receptors divided into", "total receptors divided into either", "receptors divided into either a", "into either a or", "either a or b", "a or b subclasses:", "b subclasses: epha 1", "subclasses: epha 1 8", "epha 1 8 and", "8 and 10 and", "and 10 and ephb", "and ephb 1 4", "ephb 1 4 and", "1 4 and 6 .", "4 and 6 . eph", "and 6 . eph receptors", "6 . eph receptors can", ". eph receptors can have", "eph receptors can have overlapping", "receptors can have overlapping functions", "have overlapping functions and", "overlapping functions and loss", "functions and loss of", "and loss of one receptor", "loss of one receptor can", "of one receptor can be", "one receptor can be partially", "receptor can be partially compensated", "can be partially compensated for", "be partially compensated for by", "partially compensated for by another", "compensated for by another eph", "for by another eph receptor", "by another eph receptor that", "another eph receptor that has", "eph receptor that has similar", "receptor that has similar expression", "that has similar expression pattern", "has similar expression pattern and", "similar expression pattern and ligand", "expression pattern and ligand binding", "pattern and ligand binding specificities.", "and ligand binding specificities. eph", "ligand binding specificities. eph receptors", "binding specificities. eph receptors have", "specificities. eph receptors have an", "eph receptors have an n", "receptors have an n terminal", "have an n terminal extracellular", "an n terminal extracellular domain", "n terminal extracellular domain through", "terminal extracellular domain through which", "extracellular domain through which they", "domain through which they bind", "through which they bind to", "which they bind to ephrin", "they bind to ephrin ligands", "to ephrin ligands a", "ephrin ligands a short", "ligands a short transmembrane", "short transmembrane domain and", "transmembrane domain and an", "domain and an intracellular", "and an intracellular cytoplasmic signaling", "an intracellular cytoplasmic signaling structure", "intracellular cytoplasmic signaling structure containing", "cytoplasmic signaling structure containing a", "signaling structure containing a canonical", "structure containing a canonical tyrosine", "containing a canonical tyrosine kinase", "a canonical tyrosine kinase catalytic", "canonical tyrosine kinase catalytic domain", "tyrosine kinase catalytic domain as", "kinase catalytic domain as well", "catalytic domain as well as", "domain as well as other", "as well as other protein", "well as other protein interaction", "as other protein interaction sites.", "other protein interaction sites. ephrins", "protein interaction sites. ephrins are", "interaction sites. ephrins are also", "sites. ephrins are also sub", "ephrins are also sub divided", "are also sub divided into", "also sub divided into an", "sub divided into an a", "divided into an a subclass", "an a subclass a1", "a subclass a1 a5", "a1 a5 which", "a5 which are", "which are tethered to the", "are tethered to the plasma", "tethered to the plasma membrane", "to the plasma membrane by", "the plasma membrane by a", "plasma membrane by a glycosylphosphatidylinositol", "by a glycosylphosphatidylinositol gpi", "glycosylphosphatidylinositol gpi anchor", "gpi anchor and", "anchor and a b", "a b subclass b1", "b subclass b1 b3", "b1 b3 members", "b3 members of", "members of which have a", "of which have a transmembrane", "which have a transmembrane domain", "have a transmembrane domain and", "a transmembrane domain and a", "transmembrane domain and a short", "and a short highly", "a short highly conserved", "short highly conserved cytoplasmic", "highly conserved cytoplasmic tail lacking", "conserved cytoplasmic tail lacking endogenous", "cytoplasmic tail lacking endogenous catalytic", "tail lacking endogenous catalytic activity.", "lacking endogenous catalytic activity. the", "endogenous catalytic activity. the interaction", "catalytic activity. the interaction between", "activity. the interaction between eph", "the interaction between eph receptors", "interaction between eph receptors and", "between eph receptors and its", "eph receptors and its ligands", "receptors and its ligands requires", "and its ligands requires cell", "its ligands requires cell cell", "ligands requires cell cell interaction", "requires cell cell interaction since", "cell cell interaction since both", "cell interaction since both molecules", "interaction since both molecules are", "since both molecules are membrane", "both molecules are membrane bound.", "molecules are membrane bound. close", "are membrane bound. close contact", "membrane bound. close contact between", "bound. close contact between eph", "close contact between eph receptors", "contact between eph receptors and", "between eph receptors and efns", "eph receptors and efns is", "receptors and efns is required", "and efns is required for", "efns is required for signaling", "is required for signaling to", "required for signaling to occur.", "for signaling to occur. eph/efn", "signaling to occur. eph/efn initiated", "to occur. eph/efn initiated signaling", "occur. eph/efn initiated signaling occurs", "eph/efn initiated signaling occurs bi", "initiated signaling occurs bi directionally", "signaling occurs bi directionally into", "occurs bi directionally into either", "bi directionally into either eph", "into either eph or", "either eph or efn", "eph or efn expressing", "or efn expressing cells or", "efn expressing cells or axons.", "expressing cells or axons. signaling", "cells or axons. signaling into", "or axons. signaling into the", "axons. signaling into the eph", "signaling into the eph receptor", "into the eph receptor expressing", "the eph receptor expressing cell", "eph receptor expressing cell is", "receptor expressing cell is referred", "expressing cell is referred as", "cell is referred as the", "is referred as the forward", "referred as the forward signal", "as the forward signal and", "the forward signal and signaling", "forward signal and signaling into", "signal and signaling into the", "and signaling into the efn", "signaling into the efn expressing", "into the efn expressing cell", "efn expressing cell the", "expressing cell the reverse", "cell the reverse signal.", "the reverse signal. dalva", "reverse signal. dalva et", "signal. dalva et al.", "et al. 2000 grunwald", "al. 2000 grunwald et", "2000 grunwald et al.", "et al. 2004 davy", "al. 2004 davy &", "2004 davy & robbins", "& robbins 2000 cowan", "robbins 2000 cowan et", "2000 cowan et al." ] }, { 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phosphorylated following engagement", "phosphorylated following engagement of", "following engagement of fceri", "engagement of fceri on", "of fceri on mast", "fceri on mast cells.", "on mast cells. ntal", "mast cells. ntal is", "cells. ntal is functionally", "ntal is functionally and", "is functionally and topographically", "functionally and topographically different", "and topographically different from", "topographically different from lat.", "different from lat. there", "from lat. there is", "lat. there is a", "there is a considerable", "is a considerable debate", "a considerable debate on", "considerable debate on the", "debate on the role", "on the role of", "the role of ntal", "role of ntal in", "of ntal in mast", "ntal in mast cell.", "in mast cell. depending", "mast cell. depending on", "cell. depending on the", "depending on the circumstances", "the circumstances ntal", "circumstances ntal appears", "ntal appears to have", "appears to have a", "to have a dual", "have a dual 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"that ntal also shares", "ntal also shares a", "also shares a redundant", "shares a redundant function", "a redundant function with", "redundant function with lat", "function with lat to", "with lat to play", "lat to play a", "to play a positive", "play a positive role", "positive role draberova", "role draberova et", "draberova et al. 2007", "al. 2007 orr", "2007 orr &", "orr & mcvicar. 2011", "mcvicar. 2011 zhu", "2011 zhu et", "zhu et al. 2004", "al. 2004 volna", "2004 volna et", "volna et al. 2004", "et al. 2004 .", "al. 2004 . the", "2004 . the major", ". the major steps", "the major steps in", "major steps in ntal", "steps in ntal mediated", "in ntal mediated ca+2", "ntal mediated ca+2 influx", "mediated ca+2 influx involves", "influx involves ntal", "ntal > gab2", "> gab2 >", "gab2 > pi3k", "the lipid raft resident adaptor", "lipid raft resident adaptor molecules", "raft resident adaptor molecules lat1", "resident adaptor molecules lat1 and", "adaptor molecules lat1 and non", 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"expressed and phosphorylated following engagement", "and phosphorylated following engagement of", "phosphorylated following engagement of fceri", "following engagement of fceri on", "engagement of fceri on mast", "of fceri on mast cells.", "fceri on mast cells. ntal", "on mast cells. ntal is", "mast cells. ntal is functionally", "cells. ntal is functionally and", "ntal is functionally and topographically", "is functionally and topographically different", "functionally and topographically different from", "and topographically different from lat.", "topographically different from lat. there", "different from lat. there is", "from lat. there is a", "lat. there is a considerable", "there is a considerable debate", "is a considerable debate on", "a considerable debate on the", "considerable debate on the role", "debate on the role of", "on the role of ntal", "the role of ntal in", "role of ntal in mast", "of ntal in mast cell.", "ntal in mast cell. depending", "in mast cell. depending on", "mast cell. depending on the", "cell. depending on the circumstances", "on the circumstances ntal", "the circumstances ntal appears", "circumstances ntal appears to", "ntal appears to have a", "appears to have a dual", "to have a dual role", "have a dual role as", "a dual role as positive", "dual role as positive and", "role as positive and negative", "as positive and negative regulator", "positive and negative regulator of", "and negative regulator of mc", "negative regulator of mc responses", "regulator of mc responses elicited", "of mc responses elicited via", "mc responses elicited via fceri.", "responses elicited via fceri. studies", "elicited via fceri. studies conducted", "via fceri. studies conducted in", "fceri. studies conducted in bone", "studies conducted in bone marrow", "conducted in bone marrow derived", "in bone marrow derived mast", "bone marrow derived mast cells", "derived mast cells bmmcs", "cells bmmcs of", "bmmcs of mice lacking", "of mice lacking ntal displayed", 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lacking", "in mice lacking both lat", "mice lacking both lat and", "lacking both lat and ntal", "both lat and ntal showed", "lat and ntal showed severe", "and ntal showed severe block", "ntal showed severe block in", "showed severe block in fceri", "severe block in fceri mediated", "block in fceri mediated signaling", "in fceri mediated signaling than", "fceri mediated signaling than bmmcs", "mediated signaling than bmmcs deficient", "signaling than bmmcs deficient in", "than bmmcs deficient in lat", "bmmcs deficient in lat alone", "in lat alone suggesting", "lat alone suggesting that", "alone suggesting that ntal", "suggesting that ntal also shares", "that ntal also shares a", "ntal also shares a redundant", "also shares a redundant function", "shares a redundant function with", "a redundant function with lat", "redundant function with lat to", "function with lat to play", "with lat to play a", "lat to play a positive", "to play a positive role", "a positive role draberova", "positive role draberova et", "role draberova et al.", "et al. 2007 orr", "al. 2007 orr &", "2007 orr & mcvicar.", "& mcvicar. 2011 zhu", "mcvicar. 2011 zhu et", "2011 zhu et al.", "et al. 2004 volna", "al. 2004 volna et", "2004 volna et al.", "volna et al. 2004 .", "et al. 2004 . the", "al. 2004 . the major", "2004 . the major steps", ". the major steps in", "the major steps in ntal", "major steps in ntal mediated", "steps in ntal mediated ca+2", "in ntal mediated ca+2 influx", "ntal mediated ca+2 influx involves", "ca+2 influx involves ntal", "involves ntal >", "> gab2 > pi3k" ] }, { "record_id": "GLY_000594_1_251", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2855086", "r hsa", "hsa 2855086", "r hsa 2855086" ] }, { "record_id": "GLY_000594_1_251", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ficolins bind", "bind to", "to repetitive", "repetitive carbohydrate", "carbohydrate structures", 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activation.", "activation. three", "three types", "types of", "of ficolin", "ficolin have", "have been", "been identified", "identified in", "in humans:", "humans: m", "m ficolin", "ficolin 1", "l ficolin", "ficolin 2", "and h", "h ficolin", "ficolin 3", "fcn3 .", ". fcn2", "fcn2 and", "and 3", "3 circulate", "circulate in", "in blood", "blood plasma", "plasma whereas", "whereas fcn1", "fcn1 is", "is locally", "locally secreted", "secreted by", "by immune", "immune response", "response cells", "teh et", "et al.", "al. 2000", "liu et", "al. 2005", "matsushita et", "al. 2002", "2002 .", ". plasma", "plasma ficolins", "ficolins circulate", "circulate as", "as complexes", "complexes with", "with mbl", "mbl associated", "associated serine", "serine proteases", "masps .", ". upon", "upon binding", "binding of", "of ficolins", "ficolins to", "to carbohydrates", "carbohydrates on", "masps are", "are activated", "activated and", "and subsequently", "subsequently activate", "activate the", "the 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molecules in the", "recognition molecules in the lectin", "molecules in the lectin pathway", "in the lectin pathway of", "the lectin pathway of complement", "lectin pathway of complement activation.", "pathway of complement activation. three", "of complement activation. three types", "complement activation. three types of", "activation. three types of ficolin", "three types of ficolin have", "types of ficolin have been", "of ficolin have been identified", "ficolin have been identified in", "have been identified in humans:", "been identified in humans: m", "identified in humans: m ficolin", "humans: m ficolin ficolin", "m ficolin ficolin 1", "fcn1 l ficolin", "l ficolin ficolin 2", "2 fcn2 and", "fcn2 and h ficolin", "and h ficolin ficolin", "h ficolin ficolin 3", "ficolin 3 fcn3 .", "3 fcn3 . fcn2", "fcn3 . fcn2 and 3", ". fcn2 and 3 circulate", "fcn2 and 3 circulate in", "and 3 circulate in blood", "3 circulate in blood plasma", "circulate in blood plasma whereas", "in blood plasma whereas fcn1", "blood plasma whereas fcn1 is", "plasma whereas fcn1 is locally", "whereas fcn1 is locally secreted", "fcn1 is locally secreted by", "is locally secreted by immune", "locally secreted by immune response", "secreted by immune response cells", "immune response cells teh", "response cells teh et", "cells teh et al.", "et al. 2000 liu", "al. 2000 liu et", "2000 liu et al.", "et al. 2005 matsushita", "al. 2005 matsushita et", "2005 matsushita et al.", "matsushita et al. 2002 .", "et al. 2002 . plasma", "al. 2002 . plasma ficolins", "2002 . plasma ficolins circulate", ". plasma ficolins circulate as", "plasma ficolins circulate as complexes", "ficolins circulate as complexes with", "circulate as complexes with mbl", "as complexes with mbl associated", "complexes with mbl associated serine", "with mbl associated serine proteases", "associated serine proteases masps", "serine proteases masps .", "proteases masps . upon", "masps . upon binding of", ". upon binding of ficolins", "upon binding of ficolins to", "binding of ficolins to carbohydrates", "of ficolins to carbohydrates on", "ficolins to carbohydrates on the", "to carbohydrates on the target", "carbohydrates on the target cell", "target cell surface masps", "cell surface masps are", "surface masps are activated", "masps are activated and subsequently", "are activated and subsequently activate", "activated and subsequently activate the", "and subsequently activate the complement", "subsequently activate the complement cascade", "the complement cascade matsushita", "complement cascade matsushita et", "cascade matsushita et al.", "et al. 2002 gout", "al. 2002 gout et", "2002 gout et al.", "gout et al. 2009 .", "et al. 2009 . ficolins", "al. 2009 . ficolins function", "2009 . ficolins function as", ". ficolins function as trimers", "ficolins function as trimers and", "function as trimers and larger", "as trimers and larger oligomers.", "trimers and larger oligomers. ficolin", "and larger oligomers. ficolin peptide", "larger oligomers. ficolin peptide sequences", "oligomers. ficolin peptide sequences contain", "ficolin peptide sequences contain an", "peptide sequences contain an amino", "sequences contain an amino terminal", "contain an amino terminal cysteine", "an amino terminal cysteine rich", "amino terminal cysteine rich region", "cysteine rich region a", "rich region a collagen", "region a collagen like", "collagen like domain a", "like domain a neck", "domain a neck region", "a neck region and a", "neck region and a carboxy", "region and a carboxy terminal", "and a carboxy terminal fibrinogen", "a carboxy terminal fibrinogen like", "carboxy terminal fibrinogen like domain.", "terminal fibrinogen like domain. the", "fibrinogen like domain. the fibrinogen", "like domain. the fibrinogen like", "domain. the fibrinogen like domain", "the fibrinogen like domain binds", "fibrinogen like domain binds to", "like domain binds to pathogen", "binds to pathogen or", "to pathogen or apoptotic", "pathogen or apoptotic cell", "or apoptotic cell associated molecular", "apoptotic cell associated molecular patterns.", "cell associated molecular patterns. different", "associated molecular patterns. different ficolins", "molecular patterns. different ficolins have", "patterns. different ficolins have distinct", "different ficolins have distinct recognition", "ficolins have distinct recognition specificities", "distinct recognition specificities endo", "recognition specificities endo et", "specificities endo et al.", "et al. 2007 thiel", "al. 2007 thiel and", "2007 thiel and gadjeva", "and gadjeva 2009 garlatti", "gadjeva 2009 garlatti et", "2009 garlatti et al.", "garlatti et al. 2010 ." ] }, { "record_id": "GLY_000594_1_252", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2871796", "r hsa", "hsa 2871796", "r hsa 2871796" ] }, { "record_id": "GLY_000594_1_252", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fceri mediated", "mediated mapk", "mapk activation", "fceri mediated mapk", "mediated mapk activation", "fceri mediated mapk activation", "formation of", "of the", "the lat", "lat signaling", "signaling complex", "complex leads", "leads to", "to activation", "activation of", "of mapk", "mapk and", "and production", "production of", "of cytokines.", "cytokines. the", "the sequence", "sequence of", "of events", "events that", "that leads", "leads from", "from lat", "lat to", "to cytokine", "cytokine production", "production has", "has not", "not been", "been as", "as clearly", "clearly defined", "defined as", "as the", "sequence that", "to degranulation.", "degranulation. however", "the pathways", "pathways that", "that lead", "lead to", "production require", "require the", "the guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "factors sos", "sos and", "and vav", "vav that", "that regulate", "regulate gdp", "gdp gtp", "gtp exchange", 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"hsa 2871809", "r hsa 2871809" ] }, { "record_id": "GLY_000594_1_253", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fceri mediated", "mediated ca+2", "ca+2 mobilization", "fceri mediated ca+2", "mediated ca+2 mobilization", "fceri mediated ca+2 mobilization", "increase of", "of intracellular", "intracellular calcium", "calcium in", "in mast", "mast cells", "cells is", "is most", "most crucial", "crucial for", "for mast", "mast cell", "cell degranulation.", "degranulation. elevation", "elevation of", "calcium is", "is achieved", "achieved by", "by activation", "activation of", "of plc", "plc gamma.", "gamma. mast", "cells express", "express both", "both plc", "plc gamma1", "gamma1 and", "and plc", "plc gamma2", "gamma2 isoforms", "isoforms and", "and activation", "of these", "these enzymes", "enzymes leads", "leads to", "to conversion", "conversion of", "of phosphatidylinositol", "phosphatidylinositol 4", "4 5", "5 bisphosphate", "into inositol", 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while dll", "

while dll and", "dll and jag", "and jag ligands", "jag ligands are", "ligands are well", "are well established", "established canonical", "canonical notch2 ligands", "ligands there", "there is limited", "is limited evidence", "limited evidence that", "evidence that notch2", "notch2 similar", "notch1 can", "can be activated", "be activated by", "activated by cntn1", "cntn1 contactin", "a protein involved", "protein involved in", "involved in oligodendrocyte", "in oligodendrocyte maturation", "maturation hu", "hu et al.", "et al. 2003", "al. 2003 .", "2003 . mdk", "mdk midkine", "which plays an", "plays an important", "an important role", "important role in", "role in epithelial", "in epithelial to", "epithelial to mesenchymal", "to mesenchymal transition", "transition can", "can also activate", "also activate notch2", "activate notch2 signaling", "notch2 signaling and", "signaling and is", "and is able", "is able to", "able to bind", "to bind to", "bind to the", "to the extracellular", "the extracellular domain", "extracellular domain of", "notch2 but", "but the exact", "the exact mechanism", "exact mechanism of", "mechanism of mdk", "of mdk induced", "mdk induced notch2", "induced notch2 activation", "notch2 activation has", "activation has not", "has not been", "not been elucidated", "elucidated huang", "huang et al.", "et al. 2008", "2008 gungor", "gungor et al.", "et al. 2011", "al. 2011 .", "to notch1 notch2", "notch1 notch2 is", "notch2 is activated by", "is activated by delta", "activated by delta like", "by delta like and", "delta like and jagged", "like and jagged ligands", "jagged ligands dll/jag", "dll/jag expressed in", "expressed in trans on", "in trans on a", "trans on a neighboring", "on a neighboring cell", "neighboring cell shimizu", "cell shimizu et", "shimizu et al. 1999", "al. 1999 shimizu", "1999 shimizu et", "shimizu et al. 2000", "al. 2000 hicks", "2000 hicks et", "hicks et al. 2000", "al. 2000 ji", "2000 ji et", "ji et al. 2004", "et al. 2004 .", "al. 2004 . the", "2004 . the activation", ". the activation triggers", "the activation triggers cleavage", "activation triggers cleavage of", "triggers cleavage of notch2", "of notch2 first", "notch2 first by", "first by adam10 at", "by adam10 at the", "adam10 at the s2", "at the s2 cleavage", "the s2 cleavage site", "cleavage site gibb", "site gibb et", "gibb et al. 2010", "al. 2010 shimizu", "2010 shimizu et", "2000 then", "then by gamma secretase", "by gamma secretase at", "gamma secretase at the", "secretase at the s3", "at the s3 cleavage", "the s3 cleavage site", "cleavage site saxena", "site saxena et", "saxena et al. 2001", "al. 2001 de", "2001 de strooper", "de strooper et al.", "strooper et al. 1999", "1999 resulting", "resulting in the release", "in the release of", "the release of the", "release of the intracellular", "of the intracellular domain", "the intracellular domain of", "intracellular domain of notch2", "of notch2 nicd2", "nicd2 into the", "into the cytosol. nicd2", "the cytosol. nicd2 subsequently", "cytosol. nicd2 subsequently traffics", "nicd2 subsequently traffics to", "subsequently traffics to the", "traffics to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it acts", "where it acts as", "it acts as a", "acts as a transcription", "as a transcription regulator.", "a transcription regulator.

while", "transcription regulator.

while dll", "regulator.

while dll and", "

while dll and jag", "dll and jag ligands", "and jag ligands are", "jag ligands are well", "ligands are well established", "well established canonical", "established canonical notch2", "notch2 ligands there", "ligands there is", "there is limited evidence", "is limited evidence that", "limited evidence that notch2", "that notch2 similar", "notch2 similar to", "to notch1 can", "notch1 can be", "can be activated by", "be activated by cntn1", "by cntn1 contactin", "cntn1 contactin 1", "1 a", "a protein involved in", "protein involved in oligodendrocyte", "involved in oligodendrocyte maturation", "oligodendrocyte maturation hu", "maturation hu et", "hu et al. 2003", "et al. 2003 .", "al. 2003 . mdk", ". mdk midkine", "midkine which", "which plays an important", "plays an important role", "an important role in", "important role in epithelial", "role in epithelial to", "in epithelial to mesenchymal", "epithelial to mesenchymal transition", "mesenchymal transition can", "transition can also", "can also activate notch2", "also activate notch2 signaling", "activate notch2 signaling and", "notch2 signaling and is", "signaling and is able", "and is able to", "is able to bind", "able to bind to", "to bind to the", "bind to the extracellular", "to the extracellular domain", "the extracellular domain of", "extracellular domain of notch2", "of notch2 but", "notch2 but the", "but the exact mechanism", "the exact mechanism of", "exact mechanism of mdk", "mechanism of mdk induced", "of mdk induced notch2", "mdk induced notch2 activation", "induced notch2 activation has", "notch2 activation has not", "activation has not been", "has not been elucidated", "been elucidated huang", "elucidated huang et", "huang et al. 2008", "al. 2008 gungor", "2008 gungor et", "gungor et al. 2011", "et al. 2011 .", "similar to notch1 notch2", "to notch1 notch2 is", "notch1 notch2 is activated", "notch2 is activated by delta", "is activated by delta like", "activated by delta like and", "by delta like and jagged", "delta like and jagged ligands", "and jagged ligands dll/jag", "ligands dll/jag expressed", "dll/jag expressed in trans", "expressed in trans on a", "in trans on a neighboring", "trans on a neighboring cell", "a neighboring cell shimizu", "neighboring cell shimizu et", "cell shimizu et al.", "et al. 1999 shimizu", "al. 1999 shimizu et", "1999 shimizu et al.", "et al. 2000 hicks", "al. 2000 hicks et", "2000 hicks et al.", "et al. 2000 ji", "al. 2000 ji et", "2000 ji et al.", "ji et al. 2004 .", "et al. 2004 . the", "al. 2004 . the activation", "2004 . the activation triggers", ". the activation triggers cleavage", "the activation triggers cleavage of", "activation triggers cleavage of notch2", "cleavage of notch2 first", "of notch2 first by", "notch2 first by adam10", "first by adam10 at the", "by adam10 at the s2", "adam10 at the s2 cleavage", "at the s2 cleavage site", "s2 cleavage site gibb", "cleavage site gibb et", "site gibb et al.", "et al. 2010 shimizu", "al. 2010 shimizu et", "2010 shimizu et al.", "al. 2000 then", "2000 then by", "then by gamma secretase at", "by gamma secretase at the", "gamma secretase at the s3", "secretase at the s3 cleavage", "at the s3 cleavage site", "s3 cleavage site saxena", "cleavage site saxena et", "site saxena et al.", "et al. 2001 de", "al. 2001 de strooper", "2001 de strooper et", "de strooper et al. 1999", "al. 1999 resulting", "1999 resulting in", "resulting in the release of", "in the release of the", "the release of the intracellular", "release of the intracellular domain", "of the intracellular domain of", "the intracellular domain of notch2", "domain of notch2 nicd2", "notch2 nicd2 into", "nicd2 into the cytosol.", "into the cytosol. nicd2 subsequently", "the cytosol. nicd2 subsequently traffics", "cytosol. nicd2 subsequently traffics to", "nicd2 subsequently traffics to the", "subsequently traffics to the nucleus", "traffics to the nucleus where", "to the nucleus where it", "the nucleus where it acts", "nucleus where it acts as", "where it acts as a", "it acts as a transcription", "acts as a transcription regulator.", "as a transcription regulator.

while", "a transcription regulator.

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while dll and", "regulator.

while dll and jag", "

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the", "2008 .

the cell", ".

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the", "marinkovitch 2008 .

the cell", "2008 .

the cell adhesion", ".

the cell adhesion properties", "cell adhesion properties of", "adhesion properties of laminins", "properties of laminins are", "of laminins are mediated", "laminins are mediated primarily", "are mediated primarily through", "mediated primarily through the", "primarily through the alpha", "through the alpha chain", "the alpha chain g", "alpha chain g domain", "chain g domain to", "g domain to integrins", "to integrins dystroglycan", "dystroglycan lutheran glycoprotein", "lutheran glycoprotein or", "glycoprotein or sulfated", "or sulfated glycolipids. the", "sulfated glycolipids. the n", "glycolipids. the n terminal", "the n terminal globular", "n terminal globular domains", "terminal globular domains of", "globular domains of the", "domains of the alpha", "of the alpha 1", "alpha 1 colognato", "1 colognato pyke", "colognato pyke et al.", "pyke et al. 1995", "al. 1995 and", "1995 and alpha", "and alpha 2 chains", "2 chains colognato", "chains colognato et", "colognato et al. 1997", "al. 1997 and", "1997 and globular", "and globular domains vi", "domains vi nielsen", "vi nielsen &", "nielsen & yamada 2001", "yamada 2001 and", "2001 and iva", "and iva sasaki", "iva sasaki &", "sasaki & timpl 2001", "timpl 2001 of", "2001 of the", "of the alpha 5", "the alpha 5 chain", "alpha 5 chain can", "5 chain can bind", "chain can bind to", "can bind to several", "bind to several integrin", "to several integrin isoforms", "integrin isoforms alpha1beta1", "alpha2beta1 alpha3beta1", "alpha3beta1 and alphavbeta3", "alphavbeta3 which", "which enables cell binding", "enables cell binding at", "cell binding at both", "binding at both ends", "at both ends of", "both ends of laminins", "ends of laminins with", "of laminins with these", "laminins with these alpha", "with these alpha chains.", "laminins are a large family", "are a large family of", "a large family of conserved", "family of conserved multidomain", "of conserved multidomain trimeric", "conserved multidomain trimeric basement", "multidomain trimeric basement membrane proteins.", "trimeric basement membrane proteins. there", "basement membrane proteins. there are", "membrane proteins. there are many", "proteins. there are many theoretical", "there are many theoretical trimer", "are many theoretical trimer combinations", "many theoretical trimer combinations but", "theoretical trimer combinations but only", "trimer combinations but only 18", "combinations but only 18 have", "but only 18 have been", "only 18 have been described", "have been described domogatskaya", "been described domogatskaya et", "described domogatskaya et al.", "et al. 2012 miner", "al. 2012 miner 2008", "miner 2008 macdonald et", "2008 macdonald et al.", "et al. 2010 and", "al. 2010 and the", "2010 and the existence", "and the existence of isoforms", "the existence of isoforms laminin", "existence of isoforms laminin 212", "of isoforms laminin 212 and/or", "isoforms laminin 212 and/or laminin", "laminin 212 and/or laminin 222", "and/or laminin 222 durbeej", "laminin 222 durbeej et", "222 durbeej et al.", "et al. 2010 awaits", "al. 2010 awaits further", "2010 awaits further confirmation.", "awaits further confirmation. the chains", "further confirmation. the chains assemble", "confirmation. the chains assemble through", "the chains assemble through coiled", "chains assemble through coiled coil", "assemble through coiled coil domains", "through coiled coil domains at", "coiled coil domains at their", "coil domains at their c", "domains at their c terminal", "at their c terminal end.", "their c terminal end. alpha", "c terminal end. alpha chains", "terminal end. alpha chains additionally", "end. alpha chains additionally have", "alpha chains additionally have a", "chains additionally have a large", "additionally have a large c", "have a large c terminal", "a large c terminal globular", "large c terminal globular domain", "c terminal globular domain containing", "terminal globular domain containing five", "globular domain containing five lg", "domain containing five lg subdomains", "five lg subdomains lg1", "lg subdomains lg1 5", "subdomains lg1 5 .", "lg1 5 . the n", "5 . the n termini", ". the n termini are", "the n termini are often", "n termini are often referred", "termini are often referred to", "are often referred to as", "often referred to as the", "referred to as the short", "to as the short arms.", "as the short arms. these", "the short arms. these have", "short arms. these have varying", "arms. these have varying numbers", "these have varying numbers of", "have varying numbers of laminin", "varying numbers of laminin type", "numbers of laminin type epidermal", "of laminin type epidermal growth", "laminin type epidermal growth factor", "type epidermal growth factor like", "growth factor like le", "like le repeats.", "le repeats. trimer assembly", "repeats. trimer assembly is controlled", "trimer assembly is controlled by", "assembly is controlled by highly", "is controlled by highly specific", "controlled by highly specific coiled", "by highly specific coiled coil", "highly specific coiled coil interactions", "coiled coil interactions domogatskaya", "coil interactions domogatskaya et", "interactions domogatskaya et al.", "et al. 2012 .", "al. 2012 . some", "2012 . some laminin isoforms", ". some laminin isoforms are", "some laminin isoforms are modified", "laminin isoforms are modified extracellularly", "isoforms are modified extracellularly by", "are modified extracellularly by proteolytic", "modified extracellularly by proteolytic processing", "extracellularly by proteolytic processing at", "by proteolytic processing at the", "proteolytic processing at the n", "at the n or", "the n or c", "n or c terminal", "or c terminal ends prior", "c terminal ends prior to", "terminal ends prior to their", "ends prior to their binding", "prior to their binding to", "to their binding to cellular", "their binding to cellular receptors", "binding to cellular receptors or", "to cellular receptors or other", "cellular receptors or other matrix", "receptors or other matrix molecules", "other matrix molecules tzu", "matrix molecules tzu &", "molecules tzu & marinkovitch", "tzu & marinkovitch 2008 .

the", "& marinkovitch 2008 .

the cell", "marinkovitch 2008 .

the cell adhesion", "2008 .

the cell adhesion properties", ".

the cell adhesion properties of", "cell adhesion properties of laminins", "adhesion properties of laminins are", "properties of laminins are mediated", "of laminins are mediated primarily", "laminins are mediated primarily through", "are mediated primarily through the", "mediated primarily through the alpha", "primarily through the alpha chain", "through the alpha chain g", "the alpha chain g domain", "alpha chain g domain to", "chain g domain to integrins", "domain to integrins dystroglycan", "integrins dystroglycan lutheran", "lutheran glycoprotein or sulfated", "glycoprotein or sulfated glycolipids.", "or sulfated glycolipids. the n", "sulfated glycolipids. the n terminal", "glycolipids. the n terminal globular", "the n terminal globular domains", "n terminal globular domains of", "terminal globular domains of the", "globular domains of the alpha", "domains of the alpha 1", "the alpha 1 colognato", "alpha 1 colognato pyke", "1 colognato pyke et", "colognato pyke et al. 1995", "et al. 1995 and", "al. 1995 and alpha", "1995 and alpha 2", "alpha 2 chains colognato", "2 chains colognato et", "chains colognato et al.", "et al. 1997 and", "al. 1997 and globular", "1997 and globular domains", "globular domains vi nielsen", "domains vi nielsen &", "vi nielsen & yamada", "& yamada 2001 and", "yamada 2001 and iva", "and iva sasaki &", "iva sasaki & timpl", "& timpl 2001 of", "timpl 2001 of the", "2001 of the alpha", "of the alpha 5 chain", "the alpha 5 chain can", "alpha 5 chain can bind", "5 chain can bind to", "chain can bind to several", "can bind to several integrin", "bind to several integrin isoforms", "several integrin isoforms alpha1beta1", "isoforms alpha1beta1 alpha2beta1", "and alphavbeta3 which", "alphavbeta3 which enables", "which enables cell binding at", "enables cell binding at both", "cell binding at both ends", "binding at both ends of", "at both ends of laminins", "both ends of laminins with", "ends of laminins with these", "of laminins with these alpha", "laminins with these alpha chains." ] }, { "record_id": "GLY_000594_1_258", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3000170", "r hsa", "hsa 3000170", "r hsa 3000170" ] }, { "record_id": "GLY_000594_1_258", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "syndecan interactions", "syndecans are", "are type", "type i", "i transmembrane", "transmembrane proteins", "with an", "an n", "n terminal", "terminal ectodomain", "ectodomain that", "that contains", "contains several", "several consensus", "consensus sequences", "sequences for", "for glycosaminoglycan", "attachment and", "and a", "a short", "short c", "c terminal", "terminal cytoplasmic", "cytoplasmic domain.", "domain. syndecan", "syndecan 1", "1 and", "3 gag", "gag attachment", "attachment sites", "sites occur", "occur in", "in two", "two distinct", "distinct clusters", "one near", "near the", "the n", "n terminus", "terminus 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"growth factor", "transforming growth", "factor beta", "vitronectin and", "and several", "several integrins.", "integrins. syndecans", "syndecans may", "may act", "act as", "as integrin", "integrin coreceptors.", "coreceptors. interactions", "interactions between", "between fibronectin", "fibronectin and", "and syndecans", "are modulated", "modulated by", "by tenascin", "tenascin c.", "c. syndecans", "syndecans bind", "bind a", "a wide", "wide variety", "of soluble", "soluble and", "and insoluble", "insoluble ligands", "inckluding extracellular", "extracellular matrix", "matrix components", "cell adhesion", "adhesion molecules", "and proteinases.", "proteinases. as", "as the", "the cleaved", "cleaved ectodomains", "ectodomains of", "of syndecans", "syndecans retain", "retain the", "the ability", "ability to", "to bind", "bind ligands", "ectodomain shedding", "shedding is", "is a", "a mechanism", "mechanism for", "for releasing", "releasing soluble", "soluble effectors", "effectors 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and smooth", "and smooth muscle", "smooth muscle cells.", "muscle cells. syndecan", "cells. syndecan 3", "syndecan 3 is", "3 is the", "syndecan of the", "of the nervous", "the nervous system", "system while", "while syndecan 4", "syndecan 4 is", "4 is ubiquitously", "is ubiquitously expressed", "ubiquitously expressed but", "expressed but at", "but at lower", "at lower levels", "lower levels than", "levels than the", "than the other", "the other syndecans", "syndecans refs", "refs in alexopoulou", "in alexopoulou et", "alexopoulou et al.", "al. 2007 .", "2007 . the", ". the core", "the core syndecan", "core syndecan protein", "syndecan protein has", "protein has three", "has three to", "three to five", "to five heparan", "five heparan sulfate", "heparan sulfate or", "sulfate or chondroitin", "or chondroitin sulfate", "chondroitin sulfate chains", "chains which", "which interact with", "interact with a", "with a variety", "a variety of", "variety of ligands", "of ligands including", 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syndecan 1", "syndecan 1 is the", "1 is the major", "is the major syndecan", "the major syndecan of", "major syndecan of epithelial", "syndecan of epithelial cells", "of epithelial cells including", "epithelial cells including vascular", "cells including vascular endothelium.", "including vascular endothelium. syndecan", "vascular endothelium. syndecan 2", "endothelium. syndecan 2 is", "syndecan 2 is present", "2 is present mostly", "is present mostly in", "present mostly in mesenchymal", "in mesenchymal neuronal", "mesenchymal neuronal and", "neuronal and smooth muscle", "and smooth muscle cells.", "smooth muscle cells. syndecan", "muscle cells. syndecan 3", "cells. syndecan 3 is", "syndecan 3 is the", "3 is the major", "major syndecan of the", "syndecan of the nervous", "of the nervous system", "nervous system while", "system while syndecan", "while syndecan 4 is", "syndecan 4 is ubiquitously", "4 is ubiquitously expressed", "is ubiquitously expressed but", "ubiquitously expressed 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vascular endothelial", "vascular endothelial growth factor", "growth factor transforming", "factor transforming growth", "transforming growth factor beta", "factor beta fibronectin", "collagen vitronectin and", "vitronectin and several integrins.", "and several integrins. syndecans", "several integrins. syndecans may", "integrins. syndecans may act", "syndecans may act as", "may act as integrin", "act as integrin coreceptors.", "as integrin coreceptors. interactions", "integrin coreceptors. interactions between", "coreceptors. interactions between fibronectin", "interactions between fibronectin and", "between fibronectin and syndecans", "fibronectin and syndecans are", "and syndecans are modulated", "syndecans are modulated by", "are modulated by tenascin", "modulated by tenascin c.", "by tenascin c. syndecans", "tenascin c. syndecans bind", "c. syndecans bind a", "syndecans bind a wide", "bind a wide variety", "a wide variety of", "wide variety of soluble", "variety of soluble and", "of soluble and insoluble", "soluble and insoluble ligands", "insoluble ligands inckluding", "ligands inckluding extracellular", "inckluding extracellular matrix components", "matrix components cell", "components cell adhesion", "adhesion molecules growth", "molecules growth factors", "growth factors cytokines", "cytokines and proteinases.", "and proteinases. as the", "proteinases. as the cleaved", "as the cleaved ectodomains", "the cleaved ectodomains of", "cleaved ectodomains of syndecans", "ectodomains of syndecans retain", "of syndecans retain the", "syndecans retain the ability", "retain the ability to", "the ability to bind", "ability to bind ligands", "bind ligands ectodomain", "ligands ectodomain shedding", "ectodomain shedding is a", "shedding is a mechanism", "is a mechanism for", "a mechanism for releasing", "mechanism for releasing soluble", "for releasing soluble effectors", "releasing soluble effectors that", "soluble effectors that may", "effectors that may compete", "that may compete for", "may compete for ligands", "compete for ligands with", "for ligands with their", "ligands with their cell", "with their cell bound", "their cell bound counterparts", "bound counterparts kainulainen", "counterparts kainulainen et", "kainulainen et al. 1998", "et al. 1998 .", "al. 1998 . shed", ". shed ectodomains", "shed ectodomains are", "ectodomains are found in", "are found in inflammatory", "found in inflammatory fluids", "inflammatory fluids subramanian", "fluids subramanian et", "subramanian et al. 1997", "al. 1997 and", "1997 and may", "and may induce the", "may induce the proliferation", "induce the proliferation of", "the proliferation of cancer", "proliferation of cancer cells", "cancer cells maeda", "cells maeda et", "maeda et al. 2004", "et al. 2004 .", "syndecans are type i transmembrane", "are type i transmembrane proteins", "i transmembrane proteins with", "transmembrane proteins with an", "proteins with an n", "with an n terminal ectodomain", "an n terminal ectodomain that", "n terminal ectodomain that contains", "terminal ectodomain that contains several", "ectodomain that contains several consensus", "that contains several consensus sequences", "contains several consensus sequences for", "several consensus sequences for glycosaminoglycan", "sequences for glycosaminoglycan gag", "glycosaminoglycan gag attachment", "gag attachment and a", "attachment and a short c", "and a short c terminal", "a short c terminal cytoplasmic", "short c terminal cytoplasmic domain.", "c terminal cytoplasmic domain. syndecan", "terminal cytoplasmic domain. syndecan 1", "cytoplasmic domain. syndecan 1 and", "syndecan 1 and 3", "1 and 3 gag", "and 3 gag attachment", "3 gag attachment sites occur", "gag attachment sites occur in", "attachment sites occur in two", "sites occur in two distinct", "occur in two distinct clusters", "two distinct clusters one", "distinct clusters one near", "clusters one near the", "one near the n terminus", "near the n 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transmembrane", "but the transmembrane and cytoplasmic", "the transmembrane and cytoplasmic domains", "transmembrane and cytoplasmic domains are", "and cytoplasmic domains are highly", "cytoplasmic domains are highly conserved.", "domains are highly conserved. syndecan", "are highly conserved. syndecan 1", "highly conserved. syndecan 1 and", "1 and 3 form", "and 3 form a", "3 form a subfamily. syndecan", "form a subfamily. syndecan core", "a subfamily. syndecan core proteins", "subfamily. syndecan core proteins form", "syndecan core proteins form dimers", "proteins form dimers choi", "form dimers choi et", "dimers choi et al.", "et al. 2007 and", "al. 2007 and at", "2007 and at least", "and at least syndecan 3", "at least syndecan 3 and", "syndecan 3 and 4", "3 and 4 form", "and 4 form oligomers", "4 form oligomers asundi", "form oligomers asundi &", "oligomers asundi & carey", "& carey 1995 shin", "carey 1995 shin et", "1995 shin et al.", "shin et al. 2012 .", "al. 2012 . syndecan", 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act as integrin coreceptors.", "act as integrin coreceptors. interactions", "as integrin coreceptors. interactions between", "integrin coreceptors. interactions between fibronectin", "coreceptors. interactions between fibronectin and", "interactions between fibronectin and syndecans", "between fibronectin and syndecans are", "fibronectin and syndecans are modulated", "and syndecans are modulated by", "syndecans are modulated by tenascin", "are modulated by tenascin c.", "modulated by tenascin c. syndecans", "by tenascin c. syndecans bind", "tenascin c. syndecans bind a", "c. syndecans bind a wide", "syndecans bind a wide variety", "bind a wide variety of", "a wide variety of soluble", "wide variety of soluble and", "variety of soluble and insoluble", "of soluble and insoluble ligands", "and insoluble ligands inckluding", "insoluble ligands inckluding extracellular", "ligands inckluding extracellular matrix", "extracellular matrix components cell", "matrix components cell adhesion", "components cell adhesion molecules", "cell adhesion molecules growth", "adhesion molecules growth factors", "factors cytokines and", "cytokines and proteinases. as", "and proteinases. as the cleaved", "proteinases. as the cleaved ectodomains", "as the cleaved ectodomains of", "the cleaved ectodomains of syndecans", "cleaved ectodomains of syndecans retain", "ectodomains of syndecans retain the", "of syndecans retain the ability", "syndecans retain the ability to", "retain the ability to bind", "the ability to bind ligands", "to bind ligands ectodomain", "bind ligands ectodomain shedding", "ligands ectodomain shedding is", "ectodomain shedding is a mechanism", "shedding is a mechanism for", "is a mechanism for releasing", "a mechanism for releasing soluble", "mechanism for releasing soluble effectors", "for releasing soluble effectors that", "releasing soluble effectors that may", "soluble effectors that may compete", "effectors that may compete for", "that may compete for ligands", 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et al.", "in dou et al. 2011", "et al. 2011 bekker", "al. 2011 bekker jensen", "2011 bekker jensen and", "bekker jensen and mailand 2011", "and mailand 2011 ulrich", "mailand 2011 ulrich 2012", "ulrich 2012 psakhye and", "2012 psakhye and jentsch", "and jentsch 2012 bologna", "jentsch 2012 bologna and", "2012 bologna and ferrari", "and ferrari 2013 flotho", "ferrari 2013 flotho and", "2013 flotho and melchior", "and melchior 2013 jackson", "melchior 2013 jackson and", "2013 jackson and durocher", "jackson and durocher 2013 .", "and durocher 2013 . sumoylation", "durocher 2013 . sumoylation can", "2013 . sumoylation can alter", ". sumoylation can alter enzymatic", "sumoylation can alter enzymatic activity", "can alter enzymatic activity and", "alter enzymatic activity and protein", "enzymatic activity and protein stability", "activity and protein stability or", "and protein stability or it", "protein stability or it can", "stability or it can serve", "or it can serve to", "it can serve to recruit", "can serve to recruit additional", "serve to recruit additional factors.", "to recruit additional factors. for", "recruit additional factors. for example", "factors. for example sumoylation", "for example sumoylation of", "example sumoylation of thymine", "sumoylation of thymine dna glycosylase", "thymine dna glycosylase tdg", "glycosylase tdg causes", "tdg causes tdg to", "causes tdg to lose affinity", "tdg to lose affinity for", "to lose affinity for its", "lose affinity for its product", "for its product an", "its product an abasic", "product an abasic site", "an abasic site opposite a", "abasic site opposite a g", "site opposite a g residue", "a g residue and", "g residue and thus", "residue and thus increases", "and thus increases turnover of", "thus increases turnover of the", "increases turnover of the enzyme.", "turnover of the enzyme. during", "of the enzyme. during repair", "the enzyme. during repair of", "enzyme. during repair of double", "during repair of double strand", "repair of double strand breaks", "of double strand breaks sumo1", "strand breaks sumo1 sumo2", "sumo1 sumo2 sumo3", "sumo2 sumo3 and", "sumo3 and the sumo", "and the sumo e3 ligases", "the sumo e3 ligases pias1", "sumo e3 ligases pias1 and", "e3 ligases pias1 and pias4", "ligases pias1 and pias4 accumulate", "pias1 and pias4 accumulate at", "and pias4 accumulate at double", "pias4 accumulate at double strand", "accumulate at double strand breaks", "at double strand breaks where", "double strand breaks where brca1", "breaks where brca1 herc1", "brca1 herc1 rnf168", "herc1 rnf168 mdc1", "rnf168 mdc1 and", "mdc1 and tp53bp1 are", "and tp53bp1 are sumoylated. sumoylation", "tp53bp1 are sumoylated. sumoylation of", "are sumoylated. sumoylation of brca1", "sumoylated. sumoylation of brca1 may", "sumoylation of brca1 may increase", "of brca1 may increase its", "brca1 may increase its ubiquitin", "may increase its ubiquitin ligase", "increase its ubiquitin ligase activity", "its ubiquitin ligase activity while", "ubiquitin ligase activity while sumoylation", "ligase activity while sumoylation of", "activity while sumoylation of mdc1", "while sumoylation of mdc1 and", "sumoylation of mdc1 and herc2", "of mdc1 and herc2 appears", "mdc1 and herc2 appears to", "and herc2 appears to play", "herc2 appears to play a", "appears to play a role", "to play a role in", "play a role in recruitment", "a role in recruitment of", "role in recruitment of proteins", "in recruitment of proteins such", "recruitment of proteins such as", "of proteins such as rnf4", "proteins such as rnf4 and", "such as rnf4 and rnf8", "as rnf4 and rnf8 to", "rnf4 and rnf8 to double", "and rnf8 to double strand", "rnf8 to double strand breaks.", "to double strand breaks. similarly", "double strand breaks. similarly sumoylation", "strand breaks. similarly sumoylation of", "breaks. similarly sumoylation of rpa1", "sumoylation of rpa1 rpa70", "rpa1 rpa70 recruits", "rpa70 recruits rad51 in", "recruits rad51 in the homologous", "rad51 in the homologous recombination", "in the homologous recombination pathway." ] }, { "record_id": "GLY_000594_1_263", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3214815", "r hsa", "hsa 3214815", "r hsa 3214815" ] }, { "record_id": "GLY_000594_1_263", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hdacs deacetylate", "deacetylate histones", "hdacs deacetylate histones", "lysine deacetylases", "historically referred", "referred to", "to as", "as histone", "histone deacetylases", "are divided", "divided into", "into the", "the rpd3/hda1", "rpd3/hda1 metal", "metal dependent", "'classical hdac", "hdac family'", "de ruijter", "ruijter et", "et al.", "al. 2003", "verdin et", "and the", "the unrelated", "unrelated sirtuins", "milne &", "& denu", "denu 2008", "2008 .", ". phylogenetic", "phylogenetic analysis", "analysis divides", "divides human", "human kdacs", "kdacs into", "into four", "four classes", "gregoretti et", "al. 2004", "2004 :", ": class", "class i", "i includes", "includes hdac1", "3 and", "and 8", "class iia", "iia includes", "includes hdac4", "7 and", "and 9", "class iib", "iib includes", "includes hdac6", "hdac6 and", "and 10", "class iii", "iii are", "are the", "the sirtuins", "sirt1 7", "class iv", "iv has", "has one", "one member", "gao et", "al. 2002", "2002 .", ". class", "iii enzymes", "enzymes use", "use an", "an nad+", "nad+ cofactor", "cofactor to", "to perform", "perform deacetylation", "yang &", "& seto", "seto 2008", "the others", "others classes", "classes use", "use a", "a metal", "dependent mechanism", "to catalyze", "catalyze the", "the hydrolysis", "hydrolysis of", "of acetyl", "acetyl l", "l lysine", "lysine side", "side chains", "chains in", "in histone", "histone and", "and non", "non histone", "histone proteins", "proteins yielding", "yielding l", "lysine and", "and acetate.", "acetate. x", "x ray", "ray crystal", "crystal structures", "structures are", "are available", "available for", "for four", "four human", "human hdacs", "these structures", "structures have", "have conserved", "conserved active", "active site", "site residues", "suggesting a", "a common", "common catalytic", "catalytic mechanism", "lombardi et", "al. 2011", "2011 .", ". they", "they require", "require a", "a single", "single transition", "transition metal", "metal ion", "ion and", "and are", "are typically", "typically studied", "studied in", "in vitro", "vitro as", "as zn2+", "zn2+ containing", "containing enzymes", "though in", "in vivo", "vivo hdac8", "hdac8 exhibits", "exhibits increased", "increased activity", "activity when", "when substituted", "substituted with", "with fe2+", "gantt et", "al. 2006", "2006 .", ". the", "the structurally", "structurally related", "related enzyme", "enzyme acetylpolyamine", "acetylpolyamine amidohydrolase", "leipe &", "& landsman", "landsman 1997", "exhibits optimal", "optimal activity", "activity with", "with mn2+", "followed closely", "closely by", "by zn2+", "sakurada et", "al. 1996", "1996 .

hdacs", ".

hdacs are", "are often", "often part", "part of", "of multi", "multi protein", "protein transcriptional", "transcriptional complexes", "complexes that", "that are", "are recruited", "recruited to", "to gene", "gene promoters", "regulating transcription", "transcription without", "without direct", "direct dna", "dna binding.", "binding. with", "with the", "the exception", "exception of", "of hdac8", "all class", "i members", "members can", "can be", "be catalytic", "catalytic subunits", "subunits of", "of multiprotein", "multiprotein complexes", ". hdac1", "hdac1 and", "and hdac2", "hdac2 interact", "interact to", "to form", "form the", "the catalytic", "catalytic core", "core of", "of several", "several multisubunit", "multisubunit complexes", "complexes including", "including sin3", "nucleosome remodeling", "remodeling deacetylase", "and corepressor", "corepressor of", "of rest", "grozinger &", "& schreiber", "schreiber 2002", ". hdac3", "hdac3 is", "is part", "of the", "the silencing", "silencing mediator", "mediator of", "of retinoic", "retinoic acid", "acid and", "and thyroid", "thyroid hormone", "hormone receptor", "complex or", "or the", "the homologous", "homologous nuclear", "nuclear receptor", "receptor corepressor", "li et", "al. 2000", "wen et", "zhang et", "yoon et", "oberoi et", "which are", "are involved", "involved in", "in a", "a wide", "wide range", "range of", "of processes", "processes including", "including metabolism", "and circadian", "circadian rhythms", "mottis et", "al. 2013", "2013 .", ".

class", "

class iia", "iia hdacs", "shuttle between", "between the", "the nucleus", "nucleus and", "and cytoplasm", "haberland et", "al. 2009", "2009 .", "the nuclear", "nuclear export", "export of", "of class", "hdacs requires", "requires phosphorylation", "phosphorylation stimulated", "stimulated by", "by calcium", "calcium or", "or other", "other stimuli.", "stimuli. they", "they appear", "appear to", "to have", "have been", "been evolutionarily", "evolutionarily inactivated", "inactivated as", "as enzymes", "having acquired", "acquired a", "a histidine", "histidine substitution", "substitution of", "the tyrosine", "tyrosine residue", "residue in", "in the", "the active", "site of", "the mammalian", "mammalian deacetylase", "deacetylase domain", "h976 in", "in humans", "lahm et", "al. 2007", "schuetz et", "al. 2008", ". instead", "instead they", "they function", "function as", "as transcriptional", "transcriptional corepressors", "corepressors for", "for the", "the mef2", "mef2 family", "family of", "of transcription", "transcription factors", "& gregoire", "gregoire 2005", ".

histones are", "the primary", "primary substrate", "substrate for", "for most", "most hdacs", "hdacs except", "except hdac6", "hdac6 which", "which is", "is predominantly", "predominantly cytoplasmic", "cytoplasmic and", "and acts", "acts on", "on alpha", "alpha tublin", "hubbert et", "boyault et", "2007 .", ". hdacs", "hdacs also", "also deacetylate", "deacetylate proteins", "proteins such", "such as", "as p53", "bcl6 and", "and tfiif", "glozak et", "al. 2005", "2005 .

histone", ".

histone deacetylases", "deacetylases are", "are targeted", "targeted by", "by structurally", "structurally diverse", "diverse compounds", "compounds known", "known as", "as hdac", "hdac inhibitors", "marks et", "2000 .", ". these", "these can", "can induce", "induce cytodifferentiation", "cell cycle", "cycle arrest", "arrest and", "and apoptosis", "apoptosis of", "of transformed", "transformed cells", "bolden et", ". some", "some hdis", "hdis have", "have significant", "significant antitumor", "antitumor activity", "marks and", "and breslow", "breslow 2007", "ma et", "and at", "at least", "least two", "two are", "are approved", "approved anti", "anti cancer", "cancer drugs.

the", "drugs.

the coordinates", "coordinates of", "of post", "post translational", "translational modifications", "modifications represented", "represented and", "and described", "described here", "here follow", "follow uniprot", "uniprot standard", "standard practice", "practice whereby", "whereby coordinates", "coordinates refer", "refer to", "to the", "the translated", "translated protein", "protein before", "before any", "any further", "further processing.", "processing. histone", "histone literature", "literature typically", "typically refers", "refers to", "to coordinates", "the protein", "protein after", "after the", "the initiating", "initiating methionine", "methionine has", "has been", "been removed.", "removed. therefore", "therefore the", "the coordinates", "post translated", "translated residues", "residues in", "the reactome", "reactome database", "database and", "here are", "are frequently", "frequently +1", "+1 when", "when compared", "compared with", "the literature.", "deacetylases kdacs", "historically referred to", "referred to as", "to as histone", "as histone deacetylases", "deacetylases hdacs", "are divided into", "divided into the", "into the rpd3/hda1", "the rpd3/hda1 metal", "rpd3/hda1 metal dependent", "dependent 'classical", "'classical hdac family'", "family' de", "de ruijter et", "ruijter et al.", "et al. 2003", "2003 verdin", "verdin et al.", "2003 and", "and the unrelated", "the unrelated sirtuins", "sirtuins milne", "milne & denu", "& denu 2008", "denu 2008 .", "2008 . phylogenetic", ". phylogenetic analysis", "phylogenetic analysis divides", "analysis divides human", "divides human kdacs", "human kdacs into", "kdacs into four", "into four classes", "classes gregoretti", "gregoretti et al.", "et al. 2004", "al. 2004 :", "2004 : class", ": class i", "class i includes", "i includes hdac1", "hdac1 2", "2 3", "3 and 8", "8 class", "class iia includes", "iia includes hdac4", "hdac4 5", "5 7", "7 and 9", "9 class", "class iib includes", "iib includes hdac6", "includes hdac6 and", "hdac6 and 10", "10 class", "class iii are", "iii are the", "are the sirtuins", "sirtuins sirt1", "class iv has", "iv has one", "has one member", "member hdac11", "hdac11 gao", "gao et al.", "et al. 2002", "al. 2002 .", "2002 . class", ". class iii", "class iii enzymes", "iii enzymes use", "enzymes use an", "use an nad+", "an nad+ cofactor", "nad+ cofactor to", "cofactor to perform", "to perform deacetylation", "deacetylation milne", "2008 yang", "yang & seto", "& seto 2008", "the others classes", "others classes use", "classes use a", "use a metal", "a metal dependent", "metal dependent mechanism", "mechanism gregoretti", "2004 to", "to catalyze the", "catalyze the hydrolysis", "the hydrolysis of", "hydrolysis of acetyl", "of acetyl l", "acetyl l lysine", "l lysine side", "lysine side chains", "side chains in", "chains in histone", "in histone and", "histone and non", "and non histone", "non histone proteins", "histone proteins yielding", "proteins yielding l", "yielding l lysine", "l lysine and", "lysine and acetate.", "and acetate. x", "acetate. x ray", "x ray crystal", "ray crystal structures", "crystal structures are", "structures are available", "are available for", "available for four", "for four human", "four human hdacs", "hdacs these", "these structures have", "structures have conserved", "have conserved active", "conserved active site", "active site residues", "residues suggesting", "suggesting a common", "a common catalytic", "common catalytic mechanism", "mechanism lombardi", "lombardi et al.", "et al. 2011", "al. 2011 .", "2011 . they", ". they require", "they require a", "require a single", "a single transition", "single transition metal", "transition metal ion", "metal ion and", "ion and are", "and are typically", "are typically studied", "typically studied in", "studied in vitro", "in vitro as", "vitro as zn2+", "as zn2+ containing", "zn2+ containing enzymes", "enzymes though", "though in vivo", "in vivo hdac8", "vivo hdac8 exhibits", "hdac8 exhibits increased", "exhibits increased activity", "increased activity when", "activity when substituted", "when substituted with", "substituted with fe2+", "fe2+ gantt", "gantt et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the structurally", "the structurally related", "structurally related enzyme", "related enzyme acetylpolyamine", "enzyme acetylpolyamine amidohydrolase", "amidohydrolase apah", "leipe & landsman", "& landsman 1997", "1997 exhibits", "exhibits optimal activity", "optimal activity with", "activity with mn2+", "mn2+ followed", "followed closely by", "closely by zn2+", "zn2+ sakurada", "sakurada et al.", "et al. 1996", "al. 1996 .

hdacs", "1996 .

hdacs are", ".

hdacs are often", "are often part", "often part of", "part of multi", "of multi protein", "multi protein transcriptional", "protein transcriptional complexes", "transcriptional complexes that", "complexes that are", "that are recruited", "are recruited to", "recruited to gene", "to gene promoters", "promoters regulating", "regulating transcription without", "transcription without direct", "without direct dna", "direct dna binding.", "dna binding. with", "binding. with the", "with the exception", "the exception of", "exception of hdac8", "hdac8 all", "all class i", "class i members", "i members can", "members can be", "can be catalytic", "be catalytic subunits", "catalytic subunits of", "subunits of multiprotein", "of multiprotein complexes", "complexes yang", "seto 2008 .", "2008 . hdac1", ". hdac1 and", "hdac1 and hdac2", "and hdac2 interact", "hdac2 interact to", "interact to form", "to form the", "form the catalytic", "the catalytic core", "catalytic core of", "core of several", "of several multisubunit", "several multisubunit complexes", "multisubunit complexes including", "complexes including sin3", "sin3 nucleosome", "nucleosome remodeling deacetylase", "deacetylase nurd", "nurd and", "and corepressor of", "corepressor of rest", "rest corest", "corest complexes", "complexes grozinger", "grozinger & schreiber", "& schreiber 2002", "schreiber 2002 .", "2002 . hdac3", ". hdac3 is", "hdac3 is part", "is part of", "part of the", "of the silencing", "the silencing mediator", "silencing mediator of", "mediator of retinoic", "of retinoic acid", "retinoic acid and", "acid and thyroid", "and thyroid hormone", "thyroid hormone receptor", "receptor smrt", "smrt complex", "complex or the", "or the homologous", "the homologous nuclear", "homologous nuclear receptor", "nuclear receptor corepressor", "corepressor ncor", "li et al.", "et al. 2000", "2000 wen", "wen et al.", "2000 zhang", "zhang et al.", "2002 yoon", "yoon et al.", "2003 oberoi", "oberoi et al.", "2011 which", "which are involved", "are involved in", "involved in a", "in a wide", "a wide range", "wide range of", "range of processes", "of processes including", "processes including metabolism", "metabolism inflammation", "inflammation and", "and circadian rhythms", "rhythms mottis", "mottis et al.", "et al. 2013", "al. 2013 .", "2013 .

class", ".

class iia", "

class iia hdacs", "9 shuttle", "shuttle between the", "between the nucleus", "the nucleus and", "nucleus and cytoplasm", "cytoplasm yang", "2008 haberland", "haberland et al.", "et al. 2009", "al. 2009 .", "2009 . the", ". the nuclear", "the nuclear export", "nuclear export of", "export of class", "of class iia", "class iia hdacs", "iia hdacs requires", "hdacs requires phosphorylation", "requires phosphorylation stimulated", "phosphorylation stimulated by", "stimulated by calcium", "by calcium or", "calcium or other", "or other stimuli.", "other stimuli. they", "stimuli. they appear", "they appear to", "appear to have", "to have been", "have been evolutionarily", "been evolutionarily inactivated", "evolutionarily inactivated as", "inactivated as enzymes", "enzymes having", "having acquired a", "acquired a histidine", "a histidine substitution", "histidine substitution of", "substitution of the", "of the tyrosine", "the tyrosine residue", "tyrosine residue in", "residue in the", "in the active", "the active site", "active site of", "site of the", "of the mammalian", "the mammalian deacetylase", "mammalian deacetylase domain", "domain h976", "h976 in humans", "lahm et al.", "et al. 2007", "2007 schuetz", "schuetz et al.", "et al. 2008", "al. 2008 .", "2008 . instead", ". instead they", "instead they function", "they function as", "function as transcriptional", "as transcriptional corepressors", "transcriptional corepressors for", "corepressors for the", "for the mef2", "the mef2 family", "mef2 family of", "family of transcription", "of transcription factors", "factors yang", "yang & gregoire", "& gregoire 2005", "2005 .

histones", ".

histones are the", "are the primary", "the primary substrate", "primary substrate for", "substrate for most", "for most hdacs", "most hdacs except", "hdacs except hdac6", "except hdac6 which", "hdac6 which is", "which is predominantly", "is predominantly cytoplasmic", "predominantly cytoplasmic and", "cytoplasmic and acts", "and acts on", "acts on alpha", "on alpha tublin", "tublin hubbert", "hubbert et al.", "2002 zhang", "2003 boyault", "boyault et al.", "al. 2007 .", "2007 . hdacs", ". hdacs also", "hdacs also deacetylate", "also deacetylate proteins", "deacetylate proteins such", "proteins such as", "such as p53", "p53 e2f1", "e2f1 rela", "rela yy1", "yy1 tfiie", "tfiie bcl6", "bcl6 and tfiif", "tfiif glozak", "glozak et al.", "et al. 2005", "al. 2005 .

histone", "2005 .

histone deacetylases", ".

histone deacetylases are", "deacetylases are targeted", "are targeted by", "targeted by structurally", "by structurally diverse", "structurally diverse compounds", "diverse compounds known", "compounds known as", "known as hdac", "as hdac inhibitors", "inhibitors hdis", "marks et al.", "al. 2000 .", "2000 . these", ". these can", "these can induce", "can induce cytodifferentiation", "cytodifferentiation cell", "cell cycle arrest", "cycle arrest and", "arrest and apoptosis", "and apoptosis of", "apoptosis of transformed", "of transformed cells", "cells marks", "2000 bolden", "bolden et al.", "2006 . some", ". some hdis", "some hdis have", "hdis have significant", "have significant antitumor", "significant antitumor activity", "activity marks", "marks and breslow", "and breslow 2007", "2007 ma", "ma et al.", "2009 and", "and at least", "at least two", "least two are", "two are approved", "are approved anti", "approved anti cancer", "anti cancer drugs.

the", "cancer drugs.

the coordinates", "drugs.

the coordinates of", "coordinates of post", "of post translational", "post translational modifications", "translational modifications represented", "modifications represented and", "represented and described", "and described here", "described here follow", "here follow uniprot", "follow uniprot standard", "uniprot standard practice", "standard practice whereby", "practice whereby coordinates", "whereby coordinates refer", "coordinates refer to", "refer to the", "to the translated", "the translated protein", "translated protein before", "protein before any", "before any further", "any further processing.", "further processing. histone", "processing. histone literature", "histone literature typically", "literature typically refers", "typically refers to", "refers to coordinates", "to coordinates of", "coordinates of the", "of the protein", "the protein after", "protein after the", "after the initiating", "the initiating methionine", "initiating methionine has", "methionine has been", "has been removed.", "been removed. therefore", "removed. therefore the", "therefore the coordinates", "the coordinates of", "of post translated", "post translated residues", "translated residues in", "residues in the", "in the reactome", "the reactome database", "reactome database and", "database and described", "described here are", "here are frequently", "are frequently +1", "frequently +1 when", "+1 when compared", "when compared with", "compared with the", "with the literature.", "lysine deacetylases kdacs", "kdacs historically", "historically referred to as", "referred to as histone", "to as histone deacetylases", "histone deacetylases hdacs", "hdacs are", "are divided into the", "divided into the rpd3/hda1", "into the rpd3/hda1 metal", "the rpd3/hda1 metal dependent", "metal dependent 'classical", "dependent 'classical hdac", "hdac family' de", "family' de ruijter", "de ruijter et al.", "ruijter et al. 2003", "al. 2003 verdin", "2003 verdin et", "verdin et al. 2003", "al. 2003 and", "2003 and the", "and the unrelated sirtuins", "unrelated sirtuins milne", "sirtuins milne &", "milne & denu 2008", "& denu 2008 .", "denu 2008 . phylogenetic", "2008 . phylogenetic analysis", ". phylogenetic analysis divides", "phylogenetic analysis divides human", "analysis divides human kdacs", "divides human kdacs into", "human kdacs into four", "kdacs into four classes", "four classes gregoretti", "classes gregoretti et", "gregoretti et al. 2004", "et al. 2004 :", "al. 2004 : class", "2004 : class i", ": class i includes", "class i includes hdac1", "includes hdac1 2", "2 3 and", "and 8 class", "8 class iia", "class iia includes hdac4", "includes hdac4 5", "5 7 and", "and 9 class", "9 class iib", "class iib includes hdac6", "iib includes hdac6 and", "includes hdac6 and 10", "and 10 class", "10 class iii", "class iii are the", "iii are the sirtuins", "the sirtuins sirt1", "sirtuins sirt1 7", "7 class", "class iv has one", "iv has one member", "one member hdac11", "hdac11 gao et", "gao et al. 2002", "et al. 2002 .", "al. 2002 . class", "2002 . class iii", ". class iii enzymes", "class iii enzymes use", "iii enzymes use an", "enzymes use an nad+", "use an nad+ cofactor", "an nad+ cofactor to", "nad+ cofactor to perform", "cofactor to perform deacetylation", "perform deacetylation milne", "deacetylation milne &", "denu 2008 yang", "2008 yang &", "yang & seto 2008", "2008 the", "the others classes use", "others classes use a", "classes use a metal", "use a metal dependent", "a metal dependent mechanism", "dependent mechanism gregoretti", "mechanism gregoretti et", "al. 2004 to", "2004 to catalyze", "to catalyze the hydrolysis", "catalyze the hydrolysis of", "the hydrolysis of acetyl", "hydrolysis of acetyl l", "of acetyl l lysine", "acetyl l lysine side", "l lysine side chains", "lysine side chains in", "side chains in histone", "chains in histone and", "in histone and non", "histone and non histone", "and non histone proteins", "non histone proteins yielding", "histone proteins yielding l", "proteins yielding l lysine", "yielding l lysine and", "l lysine and acetate.", "lysine and acetate. x", "and acetate. x ray", "acetate. x ray crystal", "x ray crystal structures", "ray crystal structures are", "crystal structures are available", "structures are available for", "are available for four", "available for four human", "for four human hdacs", "human hdacs these", "hdacs these structures", "these structures have conserved", "structures have conserved active", "have conserved active site", "conserved active site residues", "site residues suggesting", "residues suggesting a", "suggesting a common catalytic", "a common catalytic mechanism", "catalytic mechanism lombardi", "mechanism lombardi et", "lombardi et al. 2011", "et al. 2011 .", "al. 2011 . they", "2011 . they require", ". they require a", "they require a single", "require a single transition", "a single transition metal", "single transition metal ion", "transition metal ion and", "metal ion and are", "ion and are typically", "and are typically studied", "are typically studied in", "typically studied in vitro", "studied in vitro as", "in vitro as zn2+", "vitro as zn2+ containing", "as zn2+ containing enzymes", "containing enzymes though", "enzymes though in", "though in vivo hdac8", "in vivo hdac8 exhibits", "vivo hdac8 exhibits increased", "hdac8 exhibits increased activity", "exhibits increased activity when", "increased activity when substituted", "activity when substituted with", "when substituted with fe2+", "with fe2+ gantt", "fe2+ gantt et", "gantt et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the structurally", ". the structurally related", "the structurally related enzyme", "structurally related enzyme acetylpolyamine", "related enzyme acetylpolyamine amidohydrolase", "acetylpolyamine amidohydrolase apah", "apah leipe", "leipe & landsman 1997", "landsman 1997 exhibits", "1997 exhibits optimal", "exhibits optimal activity with", "optimal activity with mn2+", "with mn2+ followed", "mn2+ followed closely", "followed closely by zn2+", "by zn2+ sakurada", "zn2+ sakurada et", "sakurada et al. 1996", "et al. 1996 .

hdacs", "al. 1996 .

hdacs are", "1996 .

hdacs are often", ".

hdacs are often part", "are often part of", "often part of multi", "part of multi protein", "of multi protein transcriptional", "multi protein transcriptional complexes", "protein transcriptional complexes that", "transcriptional complexes that are", "complexes that are recruited", "that are recruited to", "are recruited to gene", "recruited to gene promoters", "gene promoters regulating", "promoters regulating transcription", "regulating transcription without direct", "transcription without direct dna", "without direct dna binding.", "direct dna binding. with", "dna binding. with the", "binding. with the exception", "with the exception of", "the exception of hdac8", "of hdac8 all", "hdac8 all class", "all class i members", "class i members can", "i members can be", "members can be catalytic", "can be catalytic subunits", "be catalytic subunits of", "catalytic subunits of multiprotein", "subunits of multiprotein complexes", "multiprotein complexes yang", "complexes yang &", "& seto 2008 .", "seto 2008 . hdac1", "2008 . hdac1 and", ". hdac1 and hdac2", "hdac1 and hdac2 interact", "and hdac2 interact to", "hdac2 interact to form", "interact to form the", "to form the catalytic", "form the catalytic core", "the catalytic core of", "catalytic core of several", "core of several multisubunit", "of several multisubunit complexes", "several multisubunit complexes including", "multisubunit complexes including sin3", "including sin3 nucleosome", "sin3 nucleosome remodeling", "remodeling deacetylase nurd", "nurd and corepressor", "and corepressor of rest", "of rest corest", "complexes grozinger &", "grozinger & schreiber 2002", "& schreiber 2002 .", "schreiber 2002 . hdac3", "2002 . hdac3 is", ". hdac3 is part", "hdac3 is part of", "is part of the", "part of the silencing", "of the silencing mediator", "the silencing mediator of", "silencing mediator of retinoic", "mediator of retinoic acid", "of retinoic acid and", "retinoic acid and thyroid", "acid and thyroid hormone", "and thyroid hormone receptor", "hormone receptor smrt", "smrt complex or", "complex or the homologous", "or the homologous nuclear", "the homologous nuclear receptor", "homologous nuclear receptor corepressor", "receptor corepressor ncor", "ncor li", "li et al. 2000", "al. 2000 wen", "2000 wen et", "wen et al. 2000", "al. 2000 zhang", "2000 zhang et", "zhang et al. 2002", "al. 2002 yoon", "2002 yoon et", "yoon et al. 2003", "al. 2003 oberoi", "2003 oberoi et", "oberoi et al. 2011", "al. 2011 which", "2011 which are", "which are involved in", "are involved in a", "involved in a wide", "in a wide range", "a wide range of", "wide range of processes", "range of processes including", "of processes including metabolism", "including metabolism inflammation", "inflammation and circadian", "circadian rhythms mottis", "rhythms mottis et", "mottis et al. 2013", "et al. 2013 .", "al. 2013 .

class", "2013 .

class iia", ".

class iia hdacs", "hdacs hdac4", "9 shuttle between", "shuttle between the nucleus", "between the nucleus and", "the nucleus and cytoplasm", "and cytoplasm yang", "cytoplasm yang &", "seto 2008 haberland", "2008 haberland et", "haberland et al. 2009", "et al. 2009 .", "al. 2009 . the", "2009 . the nuclear", ". the nuclear export", "the nuclear export of", "nuclear export of class", "export of class iia", "of class iia hdacs", "class iia hdacs requires", "iia hdacs requires phosphorylation", "hdacs requires phosphorylation stimulated", "requires phosphorylation stimulated by", "phosphorylation stimulated by calcium", "stimulated by calcium or", "by calcium or other", "calcium or other stimuli.", "or other stimuli. they", "other stimuli. they appear", "stimuli. they appear to", "they appear to have", "appear to have been", "to have been evolutionarily", "have been evolutionarily inactivated", "been evolutionarily inactivated as", "evolutionarily inactivated as enzymes", "as enzymes having", "enzymes having acquired", "having acquired a histidine", "acquired a histidine substitution", "a histidine substitution of", "histidine substitution of the", "substitution of the tyrosine", "of the tyrosine residue", "the tyrosine residue in", "tyrosine residue in the", "residue in the active", "in the active site", "the active site of", "active site of the", "site of the mammalian", "of the mammalian deacetylase", "the mammalian deacetylase domain", "deacetylase domain h976", "domain h976 in", "humans lahm", "lahm et al. 2007", "al. 2007 schuetz", "2007 schuetz et", "schuetz et al. 2008", "et al. 2008 .", "al. 2008 . instead", "2008 . instead they", ". instead they function", "instead they function as", "they function as transcriptional", "function as transcriptional corepressors", "as transcriptional corepressors for", "transcriptional corepressors for the", "corepressors for the mef2", "for the mef2 family", "the mef2 family of", "mef2 family of transcription", "family of transcription factors", "transcription factors yang", "factors yang &", "yang & gregoire 2005", "gregoire 2005 .

histones", "2005 .

histones are", ".

histones are the primary", "are the primary substrate", "the primary substrate for", "primary substrate for most", "substrate for most hdacs", "for most hdacs except", "most hdacs except hdac6", "hdacs except hdac6 which", "except hdac6 which is", "hdac6 which is predominantly", "which is predominantly cytoplasmic", "is predominantly cytoplasmic and", "predominantly cytoplasmic and acts", "cytoplasmic and acts on", "and acts on alpha", "acts on alpha tublin", "alpha tublin hubbert", "tublin hubbert et", "hubbert et al. 2002", "al. 2002 zhang", "2002 zhang et", "zhang et al. 2003", "al. 2003 boyault", "2003 boyault et", "boyault et al. 2007", "et al. 2007 .", "al. 2007 . hdacs", "2007 . hdacs also", ". hdacs also deacetylate", "hdacs also deacetylate proteins", "also deacetylate proteins such", "deacetylate proteins such as", "proteins such as p53", "as p53 e2f1", "tfiie bcl6 and", "and tfiif glozak", "tfiif glozak et", "glozak et al. 2005", "et al. 2005 .

histone", "al. 2005 .

histone deacetylases", "2005 .

histone deacetylases are", ".

histone deacetylases are targeted", "deacetylases are targeted by", "are targeted by structurally", "targeted by structurally diverse", "by structurally diverse compounds", "structurally diverse compounds known", "diverse compounds known as", "compounds known as hdac", "known as hdac inhibitors", "hdac inhibitors hdis", "hdis marks", "marks et al. 2000", "et al. 2000 .", "al. 2000 . these", "2000 . these can", ". these can induce", "these can induce cytodifferentiation", "induce cytodifferentiation cell", "cytodifferentiation cell cycle", "cell cycle arrest and", "cycle arrest and apoptosis", "arrest and apoptosis of", "and apoptosis of transformed", "apoptosis of transformed cells", "transformed cells marks", "cells marks et", "al. 2000 bolden", "2000 bolden et", "bolden et al. 2006", "al. 2006 . some", "2006 . some hdis", ". some hdis have", "some hdis have significant", "hdis have significant antitumor", "have significant antitumor activity", "antitumor activity marks", "activity marks and", "marks and breslow 2007", "breslow 2007 ma", "2007 ma et", "ma et al. 2009", "al. 2009 and", "2009 and at", "and at least two", "at least two are", "least two are approved", "two are approved anti", "are approved anti cancer", "approved anti cancer drugs.

the", "anti cancer drugs.

the coordinates", "cancer drugs.

the coordinates of", "drugs.

the coordinates of post", "coordinates of post translational", "of post translational modifications", "post translational modifications represented", "translational modifications represented and", "modifications represented and described", "represented and described here", "and described here follow", "described here follow uniprot", "here follow uniprot standard", "follow uniprot standard practice", "uniprot standard practice whereby", "standard practice whereby coordinates", "practice whereby coordinates refer", "whereby coordinates refer to", "coordinates refer to the", "refer to the translated", "to the translated protein", "the translated protein before", "translated protein before any", "protein before any further", "before any further processing.", "any further processing. histone", "further processing. histone literature", "processing. histone literature typically", "histone literature typically refers", "literature typically refers to", "typically refers to coordinates", "refers to coordinates of", "to coordinates of the", "coordinates of the protein", "of the protein after", "the protein after the", "protein after the initiating", "after the initiating methionine", "the initiating methionine has", "initiating methionine has been", "methionine has been removed.", "has been removed. therefore", "been removed. therefore the", "removed. therefore the coordinates", "therefore the coordinates of", "the coordinates of post", "coordinates of post translated", "of post translated residues", "post translated residues in", "translated residues in the", "residues in the reactome", "in the reactome database", "the reactome database and", "reactome database and described", "database and described here", "and described here are", "described here are frequently", "here are frequently +1", "are frequently +1 when", "frequently +1 when compared", "+1 when compared with", "when compared with the", "compared with the literature.", "kdacs historically referred", "historically referred to as histone", "referred to as histone deacetylases", "as histone deacetylases hdacs", "hdacs are divided", "are divided into the rpd3/hda1", "divided into the rpd3/hda1 metal", "into the rpd3/hda1 metal dependent", "rpd3/hda1 metal dependent 'classical", "metal dependent 'classical hdac", "dependent 'classical hdac family'", "'classical hdac family' de", "hdac family' de ruijter", "family' de ruijter et", "de ruijter et al. 2003", "et al. 2003 verdin", "al. 2003 verdin et", "2003 verdin et al.", "et al. 2003 and", "al. 2003 and the", "2003 and the unrelated", "the unrelated sirtuins milne", "unrelated sirtuins milne &", "sirtuins milne & denu", "milne & denu 2008 .", "& denu 2008 . phylogenetic", "denu 2008 . phylogenetic analysis", "2008 . phylogenetic analysis divides", ". phylogenetic analysis divides human", "phylogenetic analysis divides human kdacs", "analysis divides human kdacs into", "divides human kdacs into four", "human kdacs into four classes", "into four classes gregoretti", "four classes gregoretti et", "classes gregoretti et al.", "gregoretti et al. 2004 :", "et al. 2004 : class", "al. 2004 : class i", "2004 : class i includes", ": class i includes hdac1", "i includes hdac1 2", "hdac1 2 3", "2 3 and 8", "3 and 8 class", "and 8 class iia", "8 class iia includes", "iia includes hdac4 5", "hdac4 5 7", "5 7 and 9", "7 and 9 class", "and 9 class iib", "9 class iib includes", "class iib includes hdac6 and", "iib includes hdac6 and 10", "hdac6 and 10 class", "and 10 class iii", "10 class iii are", "class iii are the sirtuins", "are the sirtuins sirt1", "the sirtuins sirt1 7", "sirt1 7 class", "7 class iv", "class iv has one member", "has one member hdac11", "member hdac11 gao", "hdac11 gao et al.", "gao et al. 2002 .", "et al. 2002 . class", "al. 2002 . class iii", "2002 . class iii enzymes", ". class iii enzymes use", "class iii enzymes use an", "iii enzymes use an nad+", "enzymes use an nad+ cofactor", "use an nad+ cofactor to", "an nad+ cofactor to perform", "nad+ cofactor to perform deacetylation", "to perform deacetylation milne", "perform deacetylation milne &", "deacetylation milne & denu", "& denu 2008 yang", "denu 2008 yang &", "2008 yang & seto", "seto 2008 the", "2008 the others", "the others classes use a", "others classes use a metal", "classes use a metal dependent", "use a metal dependent mechanism", "metal dependent mechanism gregoretti", "dependent mechanism gregoretti et", "mechanism gregoretti et al.", "et al. 2004 to", "al. 2004 to catalyze", "2004 to catalyze the", "to catalyze the hydrolysis of", "catalyze the hydrolysis of acetyl", "the hydrolysis of acetyl l", "hydrolysis of acetyl l lysine", "of acetyl l lysine side", "acetyl l lysine side chains", "l lysine side chains in", "lysine side chains in histone", "side chains in histone and", "chains in histone and non", "in histone and non histone", "histone and non histone proteins", "and non histone proteins yielding", "non histone proteins yielding l", "histone proteins yielding l lysine", "proteins yielding l lysine and", "yielding l lysine and acetate.", "l lysine and acetate. x", "lysine and acetate. x ray", "and acetate. x ray crystal", "acetate. x ray crystal structures", "x ray crystal structures are", "ray crystal structures are available", "crystal structures are available for", "structures are available for four", "are available for four human", "available for four human hdacs", "four human hdacs these", "human hdacs these structures", "hdacs these structures have", "these structures have conserved active", "structures have conserved active site", "have conserved active site residues", "active site residues suggesting", "site residues suggesting a", "residues suggesting a common", "suggesting a common catalytic mechanism", "common catalytic mechanism lombardi", "catalytic mechanism lombardi et", "mechanism lombardi et al.", "lombardi et al. 2011 .", "et al. 2011 . they", "al. 2011 . they require", "2011 . they require a", ". they require a single", "they require a single transition", "require a single transition metal", "a single transition metal ion", "single transition metal ion and", "transition metal ion and are", "metal ion and are typically", "ion and are typically studied", "and are typically studied in", "are typically studied in vitro", "typically studied in vitro as", "studied in vitro as zn2+", "in vitro as zn2+ containing", "vitro as zn2+ containing enzymes", "zn2+ containing enzymes though", "containing enzymes though in", "enzymes though in vivo", "though in vivo hdac8 exhibits", "in vivo hdac8 exhibits increased", "vivo hdac8 exhibits increased activity", "hdac8 exhibits increased activity when", "exhibits increased activity when substituted", "increased activity when substituted with", "activity when substituted with fe2+", "substituted with fe2+ gantt", "with fe2+ gantt et", "fe2+ gantt et al.", "gantt et al. 2006 .", "et al. 2006 . the", "al. 2006 . the structurally", "2006 . the structurally related", ". the structurally related enzyme", "the structurally related enzyme acetylpolyamine", "structurally related enzyme acetylpolyamine amidohydrolase", "enzyme acetylpolyamine amidohydrolase apah", "apah leipe &", "& landsman 1997 exhibits", "landsman 1997 exhibits optimal", "1997 exhibits optimal activity", "exhibits optimal activity with mn2+", "activity with mn2+ followed", "with mn2+ followed closely", "mn2+ followed closely by", "closely by zn2+ sakurada", "by zn2+ sakurada et", "zn2+ sakurada et al.", "sakurada et al. 1996 .

hdacs", "et al. 1996 .

hdacs are", "al. 1996 .

hdacs are often", "1996 .

hdacs are often part", ".

hdacs are often part of", "are often part of multi", "often part of multi protein", "part of multi protein transcriptional", "of multi protein transcriptional complexes", "multi protein transcriptional complexes that", "protein transcriptional complexes that are", "transcriptional complexes that are recruited", "complexes that are recruited to", "that are recruited to gene", "are recruited to gene promoters", "to gene promoters regulating", "gene promoters regulating transcription", "promoters regulating transcription without", "regulating transcription without direct dna", "transcription without direct dna binding.", "without direct dna binding. with", "direct dna binding. with the", "dna binding. with the exception", "binding. with the exception of", "with the exception of hdac8", "exception of hdac8 all", "of hdac8 all class", "hdac8 all class i", "all class i members can", "class i members can be", "i members can be catalytic", "members can be catalytic subunits", "can be catalytic subunits of", "be catalytic subunits of multiprotein", "catalytic subunits of multiprotein complexes", "of multiprotein complexes yang", "multiprotein complexes yang &", "complexes yang & seto", "yang & seto 2008 .", "& seto 2008 . hdac1", "seto 2008 . hdac1 and", "2008 . hdac1 and hdac2", ". hdac1 and hdac2 interact", "hdac1 and hdac2 interact to", "and hdac2 interact to form", "hdac2 interact to form the", "interact to form the catalytic", "to form the catalytic core", "form the catalytic core of", "the catalytic core of several", "catalytic core of several multisubunit", "core of several multisubunit complexes", "of several multisubunit complexes including", "several multisubunit complexes including sin3", "complexes including sin3 nucleosome", "including sin3 nucleosome remodeling", "sin3 nucleosome remodeling deacetylase", "nucleosome remodeling deacetylase nurd", "deacetylase nurd and", "nurd and corepressor of", "corepressor of rest corest", "rest corest complexes", "corest complexes grozinger", "complexes grozinger & schreiber", "grozinger & schreiber 2002 .", "& schreiber 2002 . hdac3", "schreiber 2002 . hdac3 is", "2002 . hdac3 is part", ". hdac3 is part of", "hdac3 is part of the", "is part of the silencing", "part of the silencing mediator", "of the silencing mediator of", "the silencing mediator of retinoic", "silencing mediator of retinoic acid", "mediator of retinoic acid and", "of retinoic acid and thyroid", "retinoic acid and thyroid hormone", "acid and thyroid hormone receptor", "thyroid hormone receptor smrt", "receptor smrt complex", "smrt complex or the", "complex or the homologous nuclear", "or the homologous nuclear receptor", "the homologous nuclear receptor corepressor", "nuclear receptor corepressor ncor", "ncor li et", "et al. 2000 wen", "al. 2000 wen et", "2000 wen et al.", "et al. 2000 zhang", "al. 2000 zhang et", "2000 zhang et al.", "et al. 2002 yoon", "al. 2002 yoon et", "2002 yoon et al.", "et al. 2003 oberoi", "al. 2003 oberoi et", "2003 oberoi et al.", "et al. 2011 which", "al. 2011 which are", "2011 which are involved", "which are involved in a", "are involved in a wide", "involved in a wide range", "in a wide range of", "a wide range of processes", "wide range of processes including", "range of processes including metabolism", "processes including metabolism inflammation", "metabolism inflammation and", "inflammation and circadian rhythms", "and circadian rhythms mottis", "circadian rhythms mottis et", "rhythms mottis et al.", "mottis et al. 2013 .", "et al. 2013 .

class", "al. 2013 .

class iia", "2013 .

class iia hdacs", "iia hdacs hdac4", "and 9 shuttle", "9 shuttle between the", "shuttle between the nucleus and", "between the nucleus and cytoplasm", "nucleus and cytoplasm yang", "and cytoplasm yang &", "cytoplasm yang & seto", "& seto 2008 haberland", "seto 2008 haberland et", "2008 haberland et al.", "haberland et al. 2009 .", "et al. 2009 . the", "al. 2009 . the nuclear", "2009 . the nuclear export", ". the nuclear export of", "the nuclear export of class", "nuclear export of class iia", "export of class iia hdacs", "of class iia hdacs requires", "class iia hdacs requires phosphorylation", "iia hdacs requires phosphorylation stimulated", "hdacs requires phosphorylation stimulated by", "requires phosphorylation stimulated by calcium", "phosphorylation stimulated by calcium or", "stimulated by calcium or other", "by calcium or other stimuli.", "calcium or other stimuli. they", "or other stimuli. they appear", "other stimuli. they appear to", "stimuli. they appear to have", "they appear to have been", "appear to have been evolutionarily", "to have been evolutionarily inactivated", "have been evolutionarily inactivated as", "been evolutionarily inactivated as enzymes", "inactivated as enzymes having", "as enzymes having acquired", "enzymes having acquired a", "having acquired a histidine substitution", "acquired a histidine substitution of", "a histidine substitution of the", "histidine substitution of the tyrosine", "substitution of the tyrosine residue", "of the tyrosine residue in", "the tyrosine residue in the", "tyrosine residue in the active", "residue in the active site", "in the active site of", "the active site of the", "active site of the mammalian", "site of the mammalian deacetylase", "of the mammalian deacetylase domain", "mammalian deacetylase domain h976", "deacetylase domain h976 in", "domain h976 in humans", "in humans lahm", "humans lahm et", "et al. 2007 schuetz", "al. 2007 schuetz et", "2007 schuetz et al.", "schuetz et al. 2008 .", "et al. 2008 . instead", "al. 2008 . instead they", "2008 . instead they function", ". instead they function as", "instead they function as transcriptional", "they function as transcriptional corepressors", "function as transcriptional corepressors for", "as transcriptional corepressors for the", "transcriptional corepressors for the mef2", "corepressors for the mef2 family", "for the mef2 family of", "the mef2 family of transcription", "mef2 family of transcription factors", "of transcription factors yang", "transcription factors yang &", "factors yang & gregoire", "& gregoire 2005 .

histones", "gregoire 2005 .

histones are", "2005 .

histones are the", ".

histones are the primary substrate", "are the primary substrate for", "the primary substrate for most", "primary substrate for most hdacs", "substrate for most hdacs except", "for most hdacs except hdac6", "most hdacs except hdac6 which", "hdacs except hdac6 which is", "except hdac6 which is predominantly", "hdac6 which is predominantly cytoplasmic", "which is predominantly cytoplasmic and", "is predominantly cytoplasmic and acts", "predominantly cytoplasmic and acts on", "cytoplasmic and acts on alpha", "and acts on alpha tublin", "on alpha tublin hubbert", "alpha tublin hubbert et", "tublin hubbert et al.", "et al. 2002 zhang", "al. 2002 zhang et", "2002 zhang et al.", "et al. 2003 boyault", "al. 2003 boyault et", "2003 boyault et al.", "boyault et al. 2007 .", "et al. 2007 . hdacs", "al. 2007 . hdacs also", "2007 . hdacs also deacetylate", ". hdacs also deacetylate proteins", "hdacs also deacetylate proteins such", "also deacetylate proteins such as", "deacetylate proteins such as p53", "such as p53 e2f1", "p53 e2f1 rela", "e2f1 rela yy1", "rela yy1 tfiie", "yy1 tfiie bcl6", "tfiie bcl6 and tfiif", "bcl6 and tfiif glozak", "and tfiif glozak et", "tfiif glozak et al.", "glozak et al. 2005 .

histone", "et al. 2005 .

histone deacetylases", "al. 2005 .

histone deacetylases are", "2005 .

histone deacetylases are targeted", ".

histone deacetylases are targeted by", "deacetylases are targeted by structurally", "are targeted by structurally diverse", "targeted by structurally diverse compounds", "by structurally diverse compounds known", "structurally diverse compounds known as", "diverse compounds known as hdac", "compounds known as hdac inhibitors", "as hdac inhibitors hdis", "hdis marks et", "marks et al. 2000 .", "et al. 2000 . these", "al. 2000 . these can", "2000 . these can induce", ". these can induce cytodifferentiation", "can induce cytodifferentiation cell", "induce cytodifferentiation cell cycle", "cytodifferentiation cell cycle arrest", "cell cycle arrest and apoptosis", "cycle arrest and apoptosis of", "arrest and apoptosis of transformed", "and apoptosis of transformed cells", "of transformed cells marks", "transformed cells marks et", "cells marks et al.", "et al. 2000 bolden", "al. 2000 bolden et", "2000 bolden et al.", "bolden et al. 2006 .", "et al. 2006 . some", "al. 2006 . some hdis", "2006 . some hdis have", ". some hdis have significant", "some hdis have significant antitumor", "hdis have significant antitumor activity", "significant antitumor activity marks", "antitumor activity marks and", "activity marks and breslow", "and breslow 2007 ma", "breslow 2007 ma et", "2007 ma et al.", "et al. 2009 and", "al. 2009 and at", "2009 and at least", "and at least two are", "at least two are approved", "least two are approved anti", "two are approved anti cancer", "are approved anti cancer drugs.

the", "approved anti cancer drugs.

the coordinates", "anti cancer drugs.

the coordinates of", "cancer drugs.

the coordinates of post", "drugs.

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the", "discussed in this module.

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the coordinates of", "this module.

the coordinates of post", "module.

the coordinates of post translational", "coordinates of post translational modifications", "of post translational modifications represented", "post translational modifications represented and", "translational modifications represented and described", "modifications represented and described here", "represented and described here follow", "and described here follow uniprot", "described here follow uniprot standard", "here follow uniprot standard practice", "follow uniprot standard practice whereby", "uniprot standard practice whereby coordinates", "standard practice whereby coordinates refer", "practice whereby coordinates refer to", "whereby coordinates refer to the", "coordinates refer to the translated", "refer to the translated protein", "to the translated protein before", "the translated protein before any", "translated protein before any processing.", "protein before any processing. histone", "before any processing. histone literature", "any processing. histone literature typically", "processing. histone literature typically refers", "histone literature typically refers to", "literature typically refers to specific", "typically refers to specific residues", "refers to specific residues by", "to specific residues by numbers", "specific residues by numbers which", "residues by numbers which are", "by numbers which are determined", "numbers which are determined after", "which are determined after the", "are determined after the initiating", "determined after the initiating methionine", "after the initiating methionine has", "the initiating methionine has been", "initiating methionine has been removed.", "methionine has been removed. therefore", "has been removed. therefore the", "been removed. therefore the coordinates", "removed. therefore the coordinates of", "therefore the coordinates of post", "the coordinates of post translated", "coordinates of post translated residues", "of post translated residues in", "post translated residues in the", "translated residues in the reactome", "residues in the reactome database", "in the reactome database and", "the reactome database and described", "reactome database and described here", "database and described here are", "and described here are frequently", "described here are frequently +1", "here are frequently +1 when", "are frequently +1 when compared", "frequently +1 when compared to", "+1 when compared to the", "when compared to the histone", "compared to the histone literature.

set", "to the histone literature.

set domain", "the histone literature.

set domain containing", "histone literature.

set domain containing proteins", "literature.

set domain containing proteins are", "domain containing proteins are classified", "containing proteins are classified in", "proteins are classified in one", "are classified in one of", "classified in one of 7", "in one of 7 families", "of 7 families dillon", "7 families dillon et", "families dillon et al.", "dillon et al. 2005 .", "et al. 2005 . first", "al. 2005 . first to", "2005 . first to be", ". first to be discovered", "first to be discovered were", "to be discovered were the", "be discovered were the suv39", "discovered were the suv39 family", "were the suv39 family named", "the suv39 family named after", "suv39 family named after founding", "family named after founding member", "named after founding member suv39h1", "founding member suv39h1 kmt1a", "kmt1a which selectively", "which selectively methylates lysine 10", "selectively methylates lysine 10 of", "methylates lysine 10 of histone", "lysine 10 of histone h3", "of histone h3 h3k9", "h3k9 rea et", "rea et al. 2000 .", "et al. 2000 . family", "al. 2000 . family member", "2000 . family member ehmt2", "family member ehmt2 kmt1c", "ehmt2 kmt1c g9a", "kmt1c g9a is", "g9a is the predominant", "is the predominant h3k9 methyltransferase", "the predominant h3k9 methyltransferase in", "predominant h3k9 methyltransferase in mammals", "methyltransferase in mammals tachibana", "in mammals tachibana et", "mammals tachibana et al.", "tachibana et al. 2002 .", "et al. 2002 . setdb1", "2002 . setdb1 kmt1e", "setdb1 kmt1e eset", "kmt1e eset also", "eset also predominantly methylates", "predominantly methylates h3k9 most", "methylates h3k9 most effectively", "h3k9 most effectively when", "most effectively when complexed with", "effectively when complexed with atf7ip", "complexed with atf7ip mcaf", "atf7ip mcaf ham", "ham wang et", "wang et al. 2003 .", "et al. 2003 .

setd2", "2003 .

setd2 kmt3a", "

setd2 kmt3a hypb", "hypb a member", "a member of the set2", "member of the set2 family", "the set2 family specifically", "set2 family specifically methylates", "family specifically methylates histone", "specifically methylates histone h3 lysine", "methylates histone h3 lysine 37", "h3 lysine 37 h3k36", "h3k36 sun et", "sun et al. 2005 .", "et al. 2005 . whsc1", "2005 . whsc1 kmt3g", "whsc1 kmt3g nsd2", "kmt3g nsd2 mmset", "nsd2 mmset a", "mmset a member of", "a member of the same", "member of the same family", "the same family targets", "same family targets h3k36", "family targets h3k36 when", "targets h3k36 when provided with", "h3k36 when provided with nucleosome", "when provided with nucleosome substrates", "provided with nucleosome substrates but", "with nucleosome substrates but also", "nucleosome substrates but also can", "substrates but also can methylate", "but also can methylate histone", "also can methylate histone h4", "can methylate histone h4 lysine", "methylate histone h4 lysine 45", "histone h4 lysine 45 when", "lysine 45 when octameric", "45 when octameric native", "when octameric native or", "octameric native or recombinant nucleosome", "native or recombinant nucleosome substrates", "or recombinant nucleosome substrates are", "recombinant nucleosome substrates are provided", "substrates are provided li", "are provided li et", "provided li et al.", "al. 2009 dimethylation", "2009 dimethylation of", "dimethylation of histone h3 at", "of histone h3 at lysine", "histone h3 at lysine 37", "at lysine 37 h3k36me2", "37 h3k36me2 is", "h3k36me2 is thought to", "is thought to be the", "thought to be the principal", "to be the principal chromatin", "be the principal chromatin regulatory", "the principal chromatin regulatory activity", "principal chromatin regulatory activity of", "chromatin regulatory activity of whsc1", "activity of whsc1 kuo", "of whsc1 kuo et", "whsc1 kuo et al.", "kuo et al. 2011 .", "et al. 2011 . relatives", "al. 2011 . relatives nsd1", ". relatives nsd1 kmt3b", "nsd1 kmt3b and", "whsc1l1 kmt3f nsd3", "kmt3f nsd3 also", "nsd3 also methylate nucleosomal", "also methylate nucleosomal h3k36. nsd1", "methylate nucleosomal h3k36. nsd1 is", "nucleosomal h3k36. nsd1 is active", "h3k36. nsd1 is active on", "nsd1 is active on unmethylated", "is active on unmethylated or", "active on unmethylated or a", "on unmethylated or a mimetic", "unmethylated or a mimetic monomethylated", "or a mimetic monomethylated h3k36", "mimetic monomethylated h3k36 but", "monomethylated h3k36 but not", "h3k36 but not di", "but not di or", "not di or trimethylated", "di or trimethylated h3k36", "trimethylated h3k36 mimetics li", "h3k36 mimetics li et", "mimetics li et al.", "li et al. 2009 .", "et al. 2009 . human", "al. 2009 . human setd7", ". human setd7 kmt7", "setd7 kmt7 set7/9", "set7/9 not classified", "not classified within the 7", "classified within the 7 set", "within the 7 set domain", "the 7 set domain containing", "7 set domain containing families", "domain containing families mono", "containing families mono methylates", "families mono methylates lysine", "mono methylates lysine 5 of", "methylates lysine 5 of histone", "lysine 5 of histone h3", "of histone h3 h3k4", "h3k4 xiao et", "xiao et al. 2003 ." ] }, { "record_id": "GLY_000594_1_265", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3214842", "r hsa", "hsa 3214842", "r hsa 3214842" ] }, { "record_id": "GLY_000594_1_265", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hdms demethylate", "demethylate histones", "hdms demethylate histones", "histone lysine", "lysine demethylases", "are able", "able to", "to reverse", "reverse n", "n methylations", "methylations of", "of histones", "histones and", "and probably", "probably other", "other proteins.", "proteins. to", "to date", "date kdms", "kdms have", "have been", "been demonstrated", "demonstrated to", "to catalyse", "catalyse demethylation", "demethylation of", "of n", "n epsilon", "epsilon methylated", "methylated lysine", "lysine residues.", "residues. biochemically", "biochemically there", "there are", "are two", "two distinct", "distinct groups", "groups of", "demethylases with", "with different", "different catalytic", "catalytic mechanisms", "both of", "of which", "which result", "result in", "in methyl", "methyl group", "group oxidation", "oxidation to", "to produce", "produce formaldhyde.", "formaldhyde. kdm1a", "formerly known", "known as", "as lysine", "lysine specific", "specific demethylase", "demethylase 1", "belongs to", "to the", "the flavin", "flavin adenine", "adenine dinucleotide", "dependent amino", "amino oxidase", "oxidase family.", "family. the", "the kdm1a", "kdm1a reaction", "reaction mechanism", "mechanism requires", "requires a", "a protonatable", "protonatable lysine", "lysine epsilon", "epsilon amine", "amine group", "not available", "available in", "in trimethylated", "trimethylated lysines", "which consequently", "consequently are", "are not", "not kdm1", "kdm1 substrates.", "substrates. other", "other kdms", "kdms belong", "belong to", "the jumonji", "jumonji c", "domain containing", "containing family.", "family. these", "these are", "are members", "members of", "of the", "the cupin", "cupin superfamily", "superfamily of", "of mononuclear", "mononuclear fe", "dependent oxygenases", "which are", "are characterised", "characterised by", "by the", "the presence", "presence of", "of a", "a double", "double stranded", "stranded beta", "beta helix", "helix core", "core fold.", "fold. they", "they require", "require 2", "2 oxoglutarate", "and molecular", "molecular oxygen", "oxygen as", "as co", "co substrates", "in addition", "addition to", "to formaldehyde", "succinate and", "and carbon", "carbon dioxide.", "dioxide. this", "this hydroxylation", "hydroxylation based", "based mechanism", "mechanism does", "does not", "not require", "require a", "group and", "and consequently", "consequently jmjc", "jmjc containing", "containing demethylases", "demethylases are", "to demethylate", "demethylate tri", "and monomethylated", "monomethylated lysines.
the", "lysines.
the coordinates", "coordinates of", "of post", "post translational", "translational modifications", "modifications represented", "represented and", "and described", "described here", "here follow", "follow uniprot", "uniprot standard", "standard practice", "practice whereby", "whereby coordinates", "coordinates refer", "refer to", "the translated", "translated protein", "protein before", "before any", "any further", "further processing.", "processing. histone", "histone literature", "literature typically", "typically refers", "refers to", "to coordinates", "the protein", "protein after", "after the", "the initiating", "initiating methionine", "methionine has", "has been", "been removed.", "removed. therefore", "therefore the", "the coordinates", "post translated", "translated residues", "residues in", "in the", "the reactome", "reactome database", "database and", "here are", "are frequently", "frequently +1", "+1 when", "when compared", "compared with", "with the", "the literature.
in", "literature.
in general", "methylation at", "at histone", "histone h3", "h3 lysine", "lysine 5", "and lysine", "lysine 37", "including di", "and trimethylation", "trimethylation at", "at these", "these sites", "been linked", "linked to", "to actively", "actively transcribed", "transcribed genes", "reviewed in", "in martin", "martin &", "& zhang", "zhang 2005", "2005 .", ". in", "in contrast", "lysine 10", "promoter methylation", "methylation is", "is considered", "considered a", "a repressive", "repressive mark", "mark for", "for euchromatic", "euchromatic genes", "genes and", "and is", "is also", "also one", "one of", "the landmark", "landmark modifications", "modifications associated", "associated with", "with heterochromatin", "peters et", "et al.", "al. 2002", "2002 .
the", ".
the first", "first reported", "reported jmjc", "demethylases were", "were kdm2a/b", "fbxl11/10 .", ". these", "these catalyse", "of histone", "37 when", "when mono", "or di", "di methylated", "tsukada et", "al. 2006", "2006 .", ". they", "they were", "were found", "found to", "to contain", "contain a", "a jmjc", "jmjc catalytic", "catalytic domain", "previously implicated", "implicated in", "in chromatin", "chromatin dependent", "dependent functions", "clissold &", "& ponting", "ponting 2001", "2001 .", ". subsequently", "many other", "other jmjc", "jmjc enzymes", "enzymes have", "been identified", "identified and", "and discovered", "discovered to", "to have", "have lysine", "lysine demethylase", "demethylase activities", "activities with", "with distinct", "distinct methylation", "methylation site", "site and", "and state", "state specificities.", "specificities.
kdm3a/b", "are specific", "specific for", "for mono", "mono or", "10 on", "on histone", "yamane et", "kim et", "al. 2012", "2012 .", ". kdm4a", "kdm4a c", "jmjd2a c/jhdm3a", "c/jhdm3a c", "of di", "or tri", "tri methylated", "methylated histone", "h3 at", "at lysine", "cloos et", "fodor et", "with a", "a strong", "strong preference", "preference for", "for me3", "whetstine et", "al. 2007", "2007 .", ". kdm4d", "also catalyses", "catalyses demethylation", "of h3k9me2/3", "jhdm3a c", "can also", "also catalyse", "of lysine", "37 of", "klose et", ". kdm5a", "kdm5a d", "jarid1a d", "5 of", "christensen et", "lee et", "secombe et", "seward et", "iwase et", ". kdm6a", "kdm6a and", "and kdm6b", "lysine 28", "28 of", "agger et", "cho et", "de santra", "santra et", "lan et", "2007 .

kdm7a", "of mono", "10 of", "and mono", "and di", "horton et", "al. 2010", "huang et", "2010 .", ". phf8", "mono methylated", "lysine 21", "21 of", "histone h4", "loenarz et", "feng et", "kleine kohlbrecher", "kohlbrecher et", "fortschegger et", "qi et", "liu et", ". phf2", "wen et", "et al", "baba et", "al. 2011", "2011 .", ". jmjd6", "jmjd6 was", "was initially", "initially characterized", "characterized as", "as an", "an arginine", "arginine demethylase", "demethylase that", "that catalyses", "methylated arginine", "arginine 3", "3 of", "and arginine", "arginine 4", "4 of", "chang et", "although it", "it was", "was subsequently", "subsequently also", "also characterized", "as a", "a lysine", "lysine hydroxylase", "webby et", "al. 2009", "2009 .", ". n.b.", "n.b. the", "the literature.", "histone lysine demethylases", "demethylases kdms", "kdms are", "are able to", "able to reverse", "to reverse n", "reverse n methylations", "n methylations of", "methylations of histones", "of histones and", "histones and probably", "and probably other", "probably other proteins.", "other proteins. to", "proteins. to date", "to date kdms", "date kdms have", "kdms have been", "have been demonstrated", "been demonstrated to", "demonstrated to catalyse", "to catalyse demethylation", "catalyse demethylation of", "demethylation of n", "of n epsilon", "n epsilon methylated", "epsilon methylated lysine", "methylated lysine residues.", "lysine residues. biochemically", "residues. biochemically there", "biochemically there are", "there are two", "are two distinct", "two distinct groups", "distinct groups of", "groups of n", "methylated lysine demethylases", "lysine demethylases with", "demethylases with different", "with different catalytic", "different catalytic mechanisms", "mechanisms both", "both of which", "of which result", "which result in", "result in methyl", "in methyl group", "methyl group oxidation", "group oxidation to", "oxidation to produce", "to produce formaldhyde.", "produce formaldhyde. kdm1a", "kdm1a formerly", "formerly known as", "known as lysine", "as lysine specific", "lysine specific demethylase", "specific demethylase 1", "1 lsd1", "belongs to the", "to the flavin", "the flavin adenine", "flavin adenine dinucleotide", "dinucleotide fad", "fad dependent", "dependent amino oxidase", "amino oxidase family.", "oxidase family. the", "family. the kdm1a", "the kdm1a reaction", "kdm1a reaction mechanism", "reaction mechanism requires", "mechanism requires a", "requires a protonatable", "a protonatable lysine", "protonatable lysine epsilon", "lysine epsilon amine", "epsilon amine group", "group not", "not available in", "available in trimethylated", "in trimethylated lysines", "lysines which", "which consequently are", "consequently are not", "are not kdm1", "not kdm1 substrates.", "kdm1 substrates. other", "substrates. other kdms", "other kdms belong", "kdms belong to", "belong to the", "to the jumonji", "the jumonji c", "c jmjc", "domain containing family.", "containing family. these", "family. these are", "these are members", "are members of", "members of the", "of the cupin", "the cupin superfamily", "cupin superfamily of", "superfamily of mononuclear", "of mononuclear fe", "fe ii", "ii dependent", "oxygenases which", "which are characterised", "are characterised by", "characterised by the", "by the presence", "the presence of", "presence of a", "of a double", "a double stranded", "double stranded beta", "stranded beta helix", "beta helix core", "helix core fold.", "core fold. they", "fold. they require", "they require 2", "require 2 oxoglutarate", "oxoglutarate 2og", "2og and", "and molecular oxygen", "molecular oxygen as", "oxygen as co", "as co substrates", "substrates producing", "producing in", "in addition to", "addition to formaldehyde", "formaldehyde succinate", "succinate and carbon", "and carbon dioxide.", "carbon dioxide. this", "dioxide. this hydroxylation", "this hydroxylation based", "hydroxylation based mechanism", "based mechanism does", "mechanism does not", "does not require", "not require a", "require a protonatable", "amine group and", "group and consequently", "and consequently jmjc", "consequently jmjc containing", "jmjc containing demethylases", "containing demethylases are", "demethylases are able", "able to demethylate", "to demethylate tri", "di and", "and monomethylated lysines.
the", "monomethylated lysines.
the coordinates", "lysines.
the coordinates of", "coordinates of post", "of post translational", "post translational modifications", "translational modifications represented", "modifications represented and", "represented and described", "and described here", "described here follow", "here follow uniprot", "follow uniprot standard", "uniprot standard practice", "standard practice whereby", "practice whereby coordinates", "whereby coordinates refer", "coordinates refer to", "refer to the", "to the translated", "the translated protein", "translated protein before", "protein before any", "before any further", "any further processing.", "further processing. histone", "processing. histone literature", "histone literature typically", "literature typically refers", "typically refers to", "refers to coordinates", "to coordinates of", "coordinates of the", "of the protein", "the protein after", "protein after the", "after the initiating", "the initiating methionine", "initiating methionine has", "methionine has been", "has been removed.", "been removed. therefore", "removed. therefore the", "therefore the coordinates", "the coordinates of", "of post translated", "post translated residues", "translated residues in", "residues in the", "in the reactome", "the reactome database", "reactome database and", "database and described", "described here are", "here are frequently", "are frequently +1", "frequently +1 when", "+1 when compared", "when compared with", "compared with the", "with the literature.
in", "the literature.
in general", "general methylation", "methylation at histone", "at histone h3", "histone h3 lysine", "h3 lysine 5", "5 h3k4", "h3k4 and", "and lysine 37", "37 h3k36", "and trimethylation at", "trimethylation at these", "at these sites", "sites has", "has been linked", "been linked to", "linked to actively", "to actively transcribed", "actively transcribed genes", "genes reviewed", "reviewed in martin", "in martin &", "martin & zhang", "& zhang 2005", "zhang 2005 .", "2005 . in", ". in contrast", "contrast lysine", "10 h3k9", "h3k9 promoter", "promoter methylation is", "methylation is considered", "is considered a", "considered a repressive", "a repressive mark", "repressive mark for", "mark for euchromatic", "for euchromatic genes", "euchromatic genes and", "genes and is", "and is also", "is also one", "also one of", "one of the", "of the landmark", "the landmark modifications", "landmark modifications associated", "modifications associated with", "associated with heterochromatin", "heterochromatin peters", "peters et al.", "et al. 2002", "al. 2002 .
the", "2002 .
the first", ".
the first reported", "first reported jmjc", "reported jmjc containing", "containing demethylases were", "demethylases were kdm2a/b", "kdm2a/b jhdm1a/b", "jhdm1a/b fbxl11/10", "fbxl11/10 . these", ". these catalyse", "these catalyse demethylation", "demethylation of histone", "of histone h3", "h3 lysine 37", "lysine 37 when", "37 when mono", "or di methylated", "methylated h3k36me1/2", "tsukada et al.", "et al. 2006", "al. 2006 .", "2006 . they", ". they were", "they were found", "were found to", "found to contain", "to contain a", "contain a jmjc", "a jmjc catalytic", "jmjc catalytic domain", "domain previously", "previously implicated in", "implicated in chromatin", "in chromatin dependent", "chromatin dependent functions", "functions clissold", "clissold & ponting", "& ponting 2001", "ponting 2001 .", "2001 . subsequently", "subsequently many", "many other jmjc", "other jmjc enzymes", "jmjc enzymes have", "enzymes have been", "have been identified", "been identified and", "identified and discovered", "and discovered to", "discovered to have", "to have lysine", "have lysine demethylase", "lysine demethylase activities", "demethylase activities with", "activities with distinct", "with distinct methylation", "distinct methylation site", "methylation site and", "site and state", "and state specificities.", "state specificities.
kdm3a/b", "
kdm3a/b jhdm2a/b", "jhdm2a/b are", "are specific for", "specific for mono", "for mono or", "mono or di", "di methylated lysine", "methylated lysine 10", "lysine 10 on", "10 on histone", "on histone h3", "h3 h3k9me1/2", "yamane et al.", "2006 kim", "kim et al.", "et al. 2012", "al. 2012 .", "2012 . kdm4a", ". kdm4a c", "c jmjd2a", "jmjd2a c/jhdm3a c", "c catalyse", "demethylation of di", "di or", "or tri methylated", "tri methylated histone", "methylated histone h3", "histone h3 at", "h3 at lysine", "at lysine 10", "10 h3k9me2/3", "cloos et al.", "2006 fodor", "fodor et al.", "with a strong", "a strong preference", "strong preference for", "preference for me3", "me3 whetstine", "whetstine et al.", "et al. 2007", "al. 2007 .", "2007 . kdm4d", "kdm4d jmjd2d", "jmjd2d also", "also catalyses demethylation", "catalyses demethylation of", "demethylation of h3k9me2/3", "h3k9me2/3 whetstine", "2007 . kdm4a", "c jhdm3a", "c can", "can also catalyse", "also catalyse demethylation", "demethylation of lysine", "of lysine 37", "lysine 37 of", "37 of histone", "h3 h3k36me2/3", "klose et al.", "2006 . kdm5a", ". kdm5a d", "d jarid1a", "d catalyses", "tri methylated lysine", "methylated lysine 5", "lysine 5 of", "5 of histone", "h3 h3k4me2/3", "christensen et al.", "2007 klose", "2007 lee", "lee et al.", "2007 secombe", "secombe et al.", "2007 seward", "seward et al.", "2007 iwase", "iwase et al.", "2007 . kdm6a", ". kdm6a and", "kdm6a and kdm6b", "kdm6b utx/jmjd3", "utx/jmjd3 catalyse", "methylated lysine 28", "lysine 28 of", "28 of histone", "h3 h3k27me2/3", "agger et al.", "2007 cho", "cho et al.", "2007 de", "de santra et", "santra et al.", "2007 lan", "lan et al.", "al. 2007 .

kdm7a", ".

kdm7a kiaa1718/jhdm1d", "kiaa1718/jhdm1d catalyses", "demethylation of mono", "lysine 10 of", "10 of histone", "h3k9me1/2 and", "mono and", "and di methylated", "h3 h3k27me1/2", "horton et al.", "et al. 2010", "2010 huang", "huang et al.", "al. 2010 .", "2010 . phf8", "phf8 jhdm1e", "jhdm1e catalyses", "and mono methylated", "mono methylated lysine", "methylated lysine 21", "lysine 21 of", "21 of histone", "of histone h4", "h4 h4k20me1", "loenarz et al.", "2010 horton", "2010 feng", "feng et al.", "2010 kleine", "kleine kohlbrecher et", "kohlbrecher et al.", "2010 fortschegger", "fortschegger et al.", "2010 qi", "qi et al.", "2010 liu", "liu et al.", "2010 . phf2", "phf2 jhdm1e", "wen et al", "al 2010", "2010 baba", "baba et al.", "et al. 2011", "al. 2011 .", "2011 . jmjd6", ". jmjd6 was", "jmjd6 was initially", "was initially characterized", "initially characterized as", "characterized as an", "as an arginine", "an arginine demethylase", "arginine demethylase that", "demethylase that catalyses", "that catalyses demethylation", "di methylated arginine", "methylated arginine 3", "arginine 3 of", "3 of histone", "h3 h3r2me1/2", "h3r2me1/2 and", "and arginine 4", "arginine 4 of", "4 of histone", "h4 h4r3me1/2", "chang et al.", "2007 although", "although it was", "it was subsequently", "was subsequently also", "subsequently also characterized", "also characterized as", "characterized as a", "as a lysine", "a lysine hydroxylase", "hydroxylase webby", "webby et al.", "et al. 2009", "al. 2009 .", "2009 . n.b.", ". n.b. the", "n.b. the coordinates", "with the literature.", "lysine demethylases kdms", "kdms are able", "are able to reverse", "able to reverse n", "to reverse n methylations", "reverse n methylations of", "n methylations of histones", "methylations of histones and", "of histones and probably", "histones and probably other", "and probably other proteins.", "probably other proteins. to", "other proteins. to date", "proteins. to date kdms", "to date kdms have", "date kdms have been", "kdms have been demonstrated", "have been demonstrated to", "been demonstrated to catalyse", "demonstrated to catalyse demethylation", "to catalyse demethylation of", "catalyse demethylation of n", "demethylation of n epsilon", "of n epsilon methylated", "n epsilon methylated lysine", "epsilon methylated lysine residues.", "methylated lysine residues. biochemically", "lysine residues. biochemically there", "residues. biochemically there are", "biochemically there are two", "there are two distinct", "are two distinct groups", "two distinct groups of", "distinct groups of n", "groups of n epsilon", "epsilon methylated lysine demethylases", "methylated lysine demethylases with", "lysine demethylases with different", "demethylases with different catalytic", "with different catalytic mechanisms", "catalytic mechanisms both", "mechanisms both of", "both of which result", "of which result in", "which result in methyl", "result in methyl group", "in methyl group oxidation", "methyl group oxidation to", "group oxidation to produce", "oxidation to produce formaldhyde.", "to produce formaldhyde. kdm1a", "formaldhyde. kdm1a formerly", "kdm1a formerly known", "formerly known as lysine", "known as lysine specific", "as lysine specific demethylase", "lysine specific demethylase 1", "demethylase 1 lsd1", "lsd1 belongs", "belongs to the flavin", "to the flavin adenine", "the flavin adenine dinucleotide", "adenine dinucleotide fad", "fad dependent amino", "dependent amino oxidase family.", "amino oxidase family. the", "oxidase family. the kdm1a", "family. the kdm1a reaction", "the kdm1a reaction mechanism", "kdm1a reaction mechanism requires", "reaction mechanism requires a", "mechanism requires a protonatable", "requires a protonatable lysine", "a protonatable lysine epsilon", "protonatable lysine epsilon amine", "lysine epsilon amine group", "amine group not", "group not available", "not available in trimethylated", "available in trimethylated lysines", "trimethylated lysines which", "lysines which consequently", "which consequently are not", "consequently are not kdm1", "are not kdm1 substrates.", "not kdm1 substrates. other", "kdm1 substrates. other kdms", "substrates. other kdms belong", "other kdms belong to", "kdms belong to the", "belong to the jumonji", "to the jumonji c", "jumonji c jmjc", "jmjc domain", "domain containing family. these", "containing family. these are", "family. these are members", "these are members of", "are members of the", "members of the cupin", "of the cupin superfamily", "the cupin superfamily of", "cupin superfamily of mononuclear", "superfamily of mononuclear fe", "mononuclear fe ii", "ii dependent oxygenases", "dependent oxygenases which", "oxygenases which are", "which are characterised by", "are characterised by the", "characterised by the presence", "by the presence of", "the presence of a", "presence of a double", "of a double stranded", "a double stranded beta", "double stranded beta helix", "stranded beta helix core", "beta helix core fold.", "helix core fold. they", "core fold. they require", "fold. they require 2", "they require 2 oxoglutarate", "2 oxoglutarate 2og", "2og and molecular", "and molecular oxygen as", "molecular oxygen as co", "oxygen as co substrates", "co substrates producing", "producing in addition", "in addition to formaldehyde", "to formaldehyde succinate", "formaldehyde succinate and", "succinate and carbon dioxide.", "and carbon dioxide. this", "carbon dioxide. this hydroxylation", "dioxide. this hydroxylation based", "this hydroxylation based mechanism", "hydroxylation based mechanism does", "based mechanism does not", "mechanism does not require", "does not require a", "not require a protonatable", "require a protonatable lysine", "epsilon amine group and", "amine group and consequently", "group and consequently jmjc", "and consequently jmjc containing", "consequently jmjc containing demethylases", "jmjc containing demethylases are", "containing demethylases are able", "demethylases are able to", "are able to demethylate", "able to demethylate tri", "tri di", "di and monomethylated", "and monomethylated lysines.
the coordinates", "monomethylated lysines.
the coordinates of", "lysines.
the coordinates of post", "coordinates of post translational", "of post translational modifications", "post translational modifications represented", "translational modifications represented and", "modifications represented and described", "represented and described here", "and described here follow", "described here follow uniprot", "here follow uniprot standard", "follow uniprot standard practice", "uniprot standard practice whereby", "standard practice whereby coordinates", "practice whereby coordinates refer", "whereby coordinates refer to", "coordinates refer to the", "refer to the translated", "to the translated protein", "the translated protein before", "translated protein before any", "protein before any further", "before any further processing.", "any further processing. histone", "further processing. histone literature", "processing. histone literature typically", "histone literature typically refers", "literature typically refers to", "typically refers to coordinates", "refers to coordinates of", "to coordinates of the", "coordinates of the protein", "of the protein after", "the protein after the", "protein after the initiating", "after the initiating methionine", "the initiating methionine has", "initiating methionine has been", "methionine has been removed.", "has been removed. therefore", "been removed. therefore the", "removed. therefore the coordinates", "therefore the coordinates of", "the coordinates of post", "coordinates of post translated", "of post translated residues", "post translated residues in", "translated residues in the", "residues in the reactome", "in the reactome database", "the reactome database and", "reactome database and described", "database and described here", "and described here are", "described here are frequently", "here are frequently +1", "are frequently +1 when", "frequently +1 when compared", "+1 when compared with", "when compared with the", "compared with the literature.
in", "with the literature.
in general", "literature.
in general methylation", "general methylation at", "methylation at histone h3", "at histone h3 lysine", "histone h3 lysine 5", "lysine 5 h3k4", "h3k4 and lysine", "lysine 37 h3k36", "h3k36 including", "including di and", "di and trimethylation", "and trimethylation at these", "trimethylation at these sites", "these sites has", "sites has been", "has been linked to", "been linked to actively", "linked to actively transcribed", "to actively transcribed genes", "transcribed genes reviewed", "genes reviewed in", "reviewed in martin &", "in martin & zhang", "martin & zhang 2005", "& zhang 2005 .", "zhang 2005 . in", "2005 . in contrast", "in contrast lysine", "contrast lysine 10", "lysine 10 h3k9", "h3k9 promoter methylation", "promoter methylation is considered", "methylation is considered a", "is considered a repressive", "considered a repressive mark", "a repressive mark for", "repressive mark for euchromatic", "mark for euchromatic genes", "for euchromatic genes and", "euchromatic genes and is", "genes and is also", "and is also one", "is also one of", "also one of the", "one of the landmark", "of the landmark modifications", "the landmark modifications associated", "landmark modifications associated with", "modifications associated with heterochromatin", "with heterochromatin peters", "heterochromatin peters et", "peters et al. 2002", "et al. 2002 .
the", "al. 2002 .
the first", "2002 .
the first reported", ".
the first reported jmjc", "first reported jmjc containing", "reported jmjc containing demethylases", "jmjc containing demethylases were", "containing demethylases were kdm2a/b", "were kdm2a/b jhdm1a/b", "jhdm1a/b fbxl11/10 .", "fbxl11/10 . these catalyse", ". these catalyse demethylation", "these catalyse demethylation of", "catalyse demethylation of histone", "demethylation of histone h3", "of histone h3 lysine", "histone h3 lysine 37", "h3 lysine 37 when", "lysine 37 when mono", "when mono or", "di methylated h3k36me1/2", "h3k36me1/2 tsukada", "tsukada et al. 2006", "et al. 2006 .", "al. 2006 . they", "2006 . they were", ". they were found", "they were found to", "were found to contain", "found to contain a", "to contain a jmjc", "contain a jmjc catalytic", "a jmjc catalytic domain", "catalytic domain previously", "domain previously implicated", "previously implicated in chromatin", "implicated in chromatin dependent", "in chromatin dependent functions", "dependent functions clissold", "functions clissold &", "clissold & ponting 2001", "& ponting 2001 .", "ponting 2001 . subsequently", ". subsequently many", "subsequently many other", "many other jmjc enzymes", "other jmjc enzymes have", "jmjc enzymes have been", "enzymes have been identified", "have been identified and", "been identified and discovered", "identified and discovered to", "and discovered to have", "discovered to have lysine", "to have lysine demethylase", "have lysine demethylase activities", "lysine demethylase activities with", "demethylase activities with distinct", "activities with distinct methylation", "with distinct methylation site", "distinct methylation site and", "methylation site and state", "site and state specificities.", "and state specificities.
kdm3a/b", "specificities.
kdm3a/b jhdm2a/b", "jhdm2a/b are specific", "are specific for mono", "specific for mono or", "for mono or di", "mono or di methylated", "or di methylated lysine", "di methylated lysine 10", "methylated lysine 10 on", "lysine 10 on histone", "10 on histone h3", "histone h3 h3k9me1/2", "h3k9me1/2 yamane", "yamane et al. 2006", "al. 2006 kim", "2006 kim et", "kim et al. 2012", "et al. 2012 .", "al. 2012 . kdm4a", "2012 . kdm4a c", "kdm4a c jmjd2a", "c jmjd2a c/jhdm3a", "c/jhdm3a c catalyse", "c catalyse demethylation", "catalyse demethylation of di", "of di or", "di or tri", "or tri methylated histone", "tri methylated histone h3", "methylated histone h3 at", "histone h3 at lysine", "h3 at lysine 10", "lysine 10 h3k9me2/3", "h3k9me2/3 cloos", "cloos et al. 2006", "al. 2006 fodor", "2006 fodor et", "fodor et al. 2006", "2006 with", "with a strong preference", "a strong preference for", "strong preference for me3", "for me3 whetstine", "me3 whetstine et", "whetstine et al. 2007", "et al. 2007 .", "al. 2007 . kdm4d", ". kdm4d jmjd2d", "jmjd2d also catalyses", "also catalyses demethylation of", "catalyses demethylation of h3k9me2/3", "of h3k9me2/3 whetstine", "h3k9me2/3 whetstine et", "al. 2007 . kdm4a", "2007 . kdm4a c", "kdm4a c jhdm3a", "c jhdm3a c", "jhdm3a c can", "c can also", "can also catalyse demethylation", "also catalyse demethylation of", "catalyse demethylation of lysine", "demethylation of lysine 37", "of lysine 37 of", "lysine 37 of histone", "37 of histone h3", "histone h3 h3k36me2/3", "h3k36me2/3 klose", "klose et al. 2006", "al. 2006 . kdm5a", "2006 . kdm5a d", "kdm5a d jarid1a", "d jarid1a d", "jarid1a d catalyses", "d catalyses demethylation", "catalyses demethylation of di", "or tri methylated lysine", "tri methylated lysine 5", "methylated lysine 5 of", "lysine 5 of histone", "5 of histone h3", "histone h3 h3k4me2/3", "h3k4me2/3 christensen", "christensen et al. 2007", "al. 2007 klose", "2007 klose et", "klose et al. 2007", "al. 2007 lee", "2007 lee et", "lee et al. 2007", "al. 2007 secombe", "2007 secombe et", "secombe et al. 2007", "al. 2007 seward", "2007 seward et", "seward et al. 2007", "al. 2007 iwase", "2007 iwase et", "iwase et al. 2007", "al. 2007 . kdm6a", "2007 . kdm6a and", ". kdm6a and kdm6b", "and kdm6b utx/jmjd3", "utx/jmjd3 catalyse demethylation", "tri methylated lysine 28", "methylated lysine 28 of", "lysine 28 of histone", "28 of histone h3", "histone h3 h3k27me2/3", "h3k27me2/3 agger", "agger et al. 2007", "al. 2007 cho", "2007 cho et", "cho et al. 2007", "al. 2007 de", "2007 de santra", "de santra et al.", "santra et al. 2007", "al. 2007 lan", "2007 lan et", "lan et al. 2007", "et al. 2007 .

kdm7a", "2007 .

kdm7a kiaa1718/jhdm1d", "kiaa1718/jhdm1d catalyses demethylation", "catalyses demethylation of mono", "of mono or", "methylated lysine 10 of", "lysine 10 of histone", "10 of histone h3", "h3k9me1/2 and mono", "and mono and", "mono and di", "and di methylated lysine", "di methylated lysine 28", "histone h3 h3k27me1/2", "h3k27me1/2 horton", "horton et al. 2010", "al. 2010 huang", "2010 huang et", "huang et al. 2010", "et al. 2010 .", "al. 2010 . phf8", ". phf8 jhdm1e", "jhdm1e catalyses demethylation", "and mono methylated lysine", "mono methylated lysine 21", "methylated lysine 21 of", "lysine 21 of histone", "21 of histone h4", "histone h4 h4k20me1", "h4k20me1 loenarz", "loenarz et al. 2010", "al. 2010 horton", "2010 horton et", "al. 2010 feng", "2010 feng et", "feng et al. 2010", "al. 2010 kleine", "2010 kleine kohlbrecher", "kleine kohlbrecher et al.", "kohlbrecher et al. 2010", "al. 2010 fortschegger", "2010 fortschegger et", "fortschegger et al. 2010", "al. 2010 qi", "2010 qi et", "qi et al. 2010", "al. 2010 liu", "2010 liu et", "liu et al. 2010", "al. 2010 . phf2", ". phf2 jhdm1e", "h3k9me1/2 wen", "et al 2010", "2010 baba et", "baba et al. 2011", "et al. 2011 .", "al. 2011 . jmjd6", "2011 . jmjd6 was", ". jmjd6 was initially", "jmjd6 was initially characterized", "was initially characterized as", "initially characterized as an", "characterized as an arginine", "as an arginine demethylase", "an arginine demethylase that", "arginine demethylase that catalyses", "demethylase that catalyses demethylation", "that catalyses demethylation of", "or di methylated arginine", "di methylated arginine 3", "methylated arginine 3 of", "arginine 3 of histone", "3 of histone h3", "histone h3 h3r2me1/2", "h3r2me1/2 and arginine", "and arginine 4 of", "arginine 4 of histone", "4 of histone h4", "histone h4 h4r3me1/2", "h4r3me1/2 chang", "chang et al. 2007", "al. 2007 although", "2007 although it", "although it was subsequently", "it was subsequently also", "was subsequently also characterized", "subsequently also characterized as", "also characterized as a", "characterized as a lysine", "as a lysine hydroxylase", "lysine hydroxylase webby", "hydroxylase webby et", "webby et al. 2009", "et al. 2009 .", "al. 2009 . n.b.", "2009 . n.b. the", ". n.b. the coordinates", "n.b. the coordinates of", "compared with the literature.", "histone lysine demethylases kdms", "demethylases kdms are", "kdms are able to", "are able to reverse n", "able to reverse n methylations", "to reverse n methylations of", "reverse n methylations of histones", "n methylations of histones and", "methylations of histones and probably", "of histones and probably other", "histones and probably other proteins.", "and probably other proteins. to", "probably other proteins. to date", "other proteins. to date kdms", "proteins. to date kdms have", "to date kdms have been", "date kdms have been demonstrated", "kdms have been demonstrated to", "have been demonstrated to catalyse", "been demonstrated to catalyse demethylation", "demonstrated to catalyse demethylation of", "to catalyse demethylation of n", "catalyse demethylation of n epsilon", "demethylation of n epsilon methylated", "of n epsilon methylated lysine", "n epsilon methylated lysine residues.", "epsilon methylated lysine residues. biochemically", "methylated lysine residues. biochemically there", "lysine residues. biochemically there are", "residues. biochemically there are two", "biochemically there are two distinct", "there are two distinct groups", "are two distinct groups of", "two distinct groups of n", "distinct groups of n epsilon", "groups of n epsilon methylated", "n epsilon methylated lysine demethylases", "epsilon methylated lysine demethylases with", "methylated lysine demethylases with different", "lysine demethylases with different catalytic", "demethylases with different catalytic mechanisms", "different catalytic mechanisms both", "catalytic mechanisms both of", "mechanisms both of which", "both of which result in", "of which result in methyl", "which result in methyl group", "result in methyl group oxidation", "in methyl group oxidation to", "methyl group oxidation to produce", "group oxidation to produce formaldhyde.", "oxidation to produce formaldhyde. kdm1a", "produce formaldhyde. kdm1a formerly", "formaldhyde. kdm1a formerly known", "kdm1a formerly known as", "formerly known as lysine specific", "known as lysine specific demethylase", "as lysine specific demethylase 1", "specific demethylase 1 lsd1", "lsd1 belongs to", "belongs to the flavin adenine", "to the flavin adenine dinucleotide", "flavin adenine dinucleotide fad", "dinucleotide fad dependent", "fad dependent amino oxidase", "dependent amino oxidase family. the", "amino oxidase family. the kdm1a", "oxidase family. the kdm1a reaction", "family. the kdm1a reaction mechanism", "the kdm1a reaction mechanism requires", "kdm1a reaction mechanism requires a", "reaction mechanism requires a protonatable", "mechanism requires a protonatable lysine", "requires a protonatable lysine epsilon", "a protonatable lysine epsilon amine", "protonatable lysine epsilon amine group", "epsilon amine group not", "amine group not available", "group not available in", "not available in trimethylated lysines", "in trimethylated lysines which", "trimethylated lysines which consequently", "lysines which consequently are", "which consequently are not kdm1", "consequently are not kdm1 substrates.", "are not kdm1 substrates. other", "not kdm1 substrates. other kdms", "kdm1 substrates. other kdms belong", "substrates. other kdms belong to", "other kdms belong to the", "kdms belong to the jumonji", "belong to the jumonji c", "the jumonji c jmjc", "jmjc domain containing", "domain containing family. these are", "containing family. these are members", "family. these are members of", "these are members of the", "are members of the cupin", "members of the cupin superfamily", "of the cupin superfamily of", "the cupin superfamily of mononuclear", "cupin superfamily of mononuclear fe", "of mononuclear fe ii", "fe ii dependent", "dependent oxygenases which are", "oxygenases which are characterised", "which are characterised by the", "are characterised by the presence", "characterised by the presence of", "by the presence of a", "the presence of a double", "presence of a double stranded", "of a double stranded beta", "a double stranded beta helix", "double stranded beta helix core", "stranded beta helix core fold.", "beta helix core fold. they", "helix core fold. they require", "core fold. they require 2", "fold. they require 2 oxoglutarate", "require 2 oxoglutarate 2og", "oxoglutarate 2og and", "2og and molecular oxygen", "and molecular oxygen as co", "molecular oxygen as co substrates", "as co substrates producing", "substrates producing in", "producing in addition to", "addition to formaldehyde succinate", "to formaldehyde succinate and", "formaldehyde succinate and carbon", "succinate and carbon dioxide. this", "and carbon dioxide. this hydroxylation", "carbon dioxide. this hydroxylation based", "dioxide. this hydroxylation based mechanism", "this hydroxylation based mechanism does", "hydroxylation based mechanism does not", "based mechanism does not require", "mechanism does not require a", "does not require a protonatable", "not require a protonatable lysine", "require a protonatable lysine epsilon", "lysine epsilon amine group and", "epsilon amine group and consequently", "amine group and consequently jmjc", "group and consequently jmjc containing", "and consequently jmjc containing demethylases", "consequently jmjc containing demethylases are", "jmjc containing demethylases are able", "containing demethylases are able to", "demethylases are able to demethylate", "are able to demethylate tri", "demethylate tri di", "di and monomethylated lysines.
the", "and monomethylated lysines.
the coordinates of", "monomethylated lysines.
the coordinates of post", "lysines.
the coordinates of post translational", "coordinates of post translational modifications", "of post translational modifications represented", "post translational modifications represented and", "translational modifications represented and described", "modifications represented and described here", "represented and described here follow", "and described here follow uniprot", "described here follow uniprot standard", "here follow uniprot standard practice", "follow uniprot standard practice whereby", "uniprot standard practice whereby coordinates", "standard practice whereby coordinates refer", "practice whereby coordinates refer to", "whereby coordinates refer to the", "coordinates refer to the translated", "refer to the translated protein", "to the translated protein before", "the translated protein before any", "translated protein before any further", "protein before any further processing.", "before any further processing. histone", "any further processing. histone literature", "further processing. histone literature typically", "processing. histone literature typically refers", "histone literature typically refers to", "literature typically refers to coordinates", "typically refers to coordinates of", "refers to coordinates of the", "to coordinates of the protein", "coordinates of the protein after", "of the protein after the", "the protein after the initiating", "protein after the initiating methionine", "after the initiating methionine has", "the initiating methionine has been", "initiating methionine has been removed.", "methionine has been removed. therefore", "has been removed. therefore the", "been removed. therefore the coordinates", "removed. therefore the coordinates of", "therefore the coordinates of post", "the coordinates of post translated", "coordinates of post translated residues", "of post translated residues in", "post translated residues in the", "translated residues in the reactome", "residues in the reactome database", "in the reactome database and", "the reactome database and described", "reactome database and described here", "database and described here are", "and described here are frequently", "described here are frequently +1", "here are frequently +1 when", "are frequently +1 when compared", "frequently +1 when compared with", "+1 when compared with the", "when compared with the literature.
in", "compared with the literature.
in general", "the literature.
in general methylation", "literature.
in general methylation at", "general methylation at histone", "methylation at histone h3 lysine", "at histone h3 lysine 5", "h3 lysine 5 h3k4", "5 h3k4 and", "h3k4 and lysine 37", "and lysine 37 h3k36", "h3k36 including di", "including di and trimethylation", "di and trimethylation at", "and trimethylation at these sites", "at these sites has", "these sites has been", "sites has been linked", "has been linked to actively", "been linked to actively transcribed", "linked to actively transcribed genes", "actively transcribed genes reviewed", "transcribed genes reviewed in", "genes reviewed in martin", "reviewed in martin & zhang", "in martin & zhang 2005", "martin & zhang 2005 .", "& zhang 2005 . in", "zhang 2005 . in contrast", ". in contrast lysine", "in contrast lysine 10", "10 h3k9 promoter", "h3k9 promoter methylation is", "promoter methylation is considered a", "methylation is considered a repressive", "is considered a repressive mark", "considered a repressive mark for", "a repressive mark for euchromatic", "repressive mark for euchromatic genes", "mark for euchromatic genes and", "for euchromatic genes and is", "euchromatic genes and is also", "genes and is also one", "and is also one of", "is also one of the", "also one of the landmark", "one of the landmark modifications", "of the landmark modifications associated", "the landmark modifications associated with", "landmark modifications associated with heterochromatin", "associated with heterochromatin peters", "with heterochromatin peters et", "heterochromatin peters et al.", "peters et al. 2002 .
the", "et al. 2002 .
the first", "al. 2002 .
the first reported", "2002 .
the first reported jmjc", ".
the first reported jmjc containing", "first reported jmjc containing demethylases", "reported jmjc containing demethylases were", "jmjc containing demethylases were kdm2a/b", "demethylases were kdm2a/b jhdm1a/b", "kdm2a/b jhdm1a/b fbxl11/10", "jhdm1a/b fbxl11/10 . these", "fbxl11/10 . these catalyse demethylation", ". these catalyse demethylation of", "these catalyse demethylation of histone", "catalyse demethylation of histone h3", "demethylation of histone h3 lysine", "of histone h3 lysine 37", "histone h3 lysine 37 when", "h3 lysine 37 when mono", "37 when mono or", "when mono or di", "or di methylated h3k36me1/2", "h3k36me1/2 tsukada et", "tsukada et al. 2006 .", "et al. 2006 . they", "al. 2006 . they were", "2006 . they were found", ". they were found to", "they were found to contain", "were found to contain a", "found to contain a jmjc", "to contain a jmjc catalytic", "contain a jmjc catalytic domain", "jmjc catalytic domain previously", "catalytic domain previously implicated", "domain previously implicated in", "previously implicated in chromatin dependent", "implicated in chromatin dependent functions", "chromatin dependent functions clissold", "dependent functions clissold &", "functions clissold & ponting", "clissold & ponting 2001 .", "& ponting 2001 . subsequently", "2001 . subsequently many", ". subsequently many other", "subsequently many other jmjc", "many other jmjc enzymes have", "other jmjc enzymes have been", "jmjc enzymes have been identified", "enzymes have been identified and", "have been identified and discovered", "been identified and discovered to", "identified and discovered to have", "and discovered to have lysine", "discovered to have lysine demethylase", "to have lysine demethylase activities", "have lysine demethylase activities with", "lysine demethylase activities with distinct", "demethylase activities with distinct methylation", "activities with distinct methylation site", "with distinct methylation site and", "distinct methylation site and state", "methylation site and state specificities.", "site and state specificities.
kdm3a/b", "state specificities.
kdm3a/b jhdm2a/b", "
kdm3a/b jhdm2a/b are", "jhdm2a/b are specific for", "are specific for mono or", "specific for mono or di", "for mono or di methylated", "mono or di methylated lysine", "or di methylated lysine 10", "di methylated lysine 10 on", "methylated lysine 10 on histone", "lysine 10 on histone h3", "on histone h3 h3k9me1/2", "h3k9me1/2 yamane et", "et al. 2006 kim", "al. 2006 kim et", "2006 kim et al.", "kim et al. 2012 .", "et al. 2012 . kdm4a", "al. 2012 . kdm4a c", ". kdm4a c jmjd2a", "kdm4a c jmjd2a c/jhdm3a", "c jmjd2a c/jhdm3a c", "jmjd2a c/jhdm3a c catalyse", "c/jhdm3a c catalyse demethylation", "c catalyse demethylation of", "demethylation of di or", "of di or tri", "di or tri methylated", "or tri methylated histone h3", "tri methylated histone h3 at", "methylated histone h3 at lysine", "histone h3 at lysine 10", "at lysine 10 h3k9me2/3", "h3k9me2/3 cloos et", "et al. 2006 fodor", "al. 2006 fodor et", "2006 fodor et al.", "al. 2006 with", "2006 with a", "with a strong preference for", "a strong preference for me3", "preference for me3 whetstine", "for me3 whetstine et", "me3 whetstine et al.", "whetstine et al. 2007 .", "et al. 2007 . kdm4d", "2007 . kdm4d jmjd2d", "kdm4d jmjd2d also", "jmjd2d also catalyses demethylation", "also catalyses demethylation of h3k9me2/3", "demethylation of h3k9me2/3 whetstine", "of h3k9me2/3 whetstine et", "h3k9me2/3 whetstine et al.", "et al. 2007 . kdm4a", "al. 2007 . kdm4a c", ". kdm4a c jhdm3a", "kdm4a c jhdm3a c", "jhdm3a c can also", "c can also catalyse", "can also catalyse demethylation of", "also catalyse demethylation of lysine", "catalyse demethylation of lysine 37", "demethylation of lysine 37 of", "of lysine 37 of histone", "lysine 37 of histone h3", "of histone h3 h3k36me2/3", "h3k36me2/3 klose et", "klose et al. 2006 .", "et al. 2006 . kdm5a", "al. 2006 . kdm5a d", ". kdm5a d jarid1a", "kdm5a d jarid1a d", "jarid1a d catalyses demethylation", "d catalyses demethylation of", "or tri methylated lysine 5", "tri methylated lysine 5 of", "methylated lysine 5 of histone", "lysine 5 of histone h3", "of histone h3 h3k4me2/3", "h3k4me2/3 christensen et", "et al. 2007 klose", "al. 2007 klose et", "2007 klose et al.", "et al. 2007 lee", "al. 2007 lee et", "2007 lee et al.", "et al. 2007 secombe", "al. 2007 secombe et", "2007 secombe et al.", "et al. 2007 seward", "al. 2007 seward et", "2007 seward et al.", "et al. 2007 iwase", "al. 2007 iwase et", "2007 iwase et al.", "iwase et al. 2007 .", "et al. 2007 . kdm6a", "al. 2007 . kdm6a and", "2007 . kdm6a and kdm6b", "kdm6a and kdm6b utx/jmjd3", "kdm6b utx/jmjd3 catalyse", "utx/jmjd3 catalyse demethylation of", "or tri methylated lysine 28", "tri methylated lysine 28 of", "methylated lysine 28 of histone", "lysine 28 of histone h3", "of histone h3 h3k27me2/3", "h3k27me2/3 agger et", "et al. 2007 cho", "al. 2007 cho et", "2007 cho et al.", "et al. 2007 de", "al. 2007 de santra", "2007 de santra et", "de santra et al. 2007", "et al. 2007 lan", "al. 2007 lan et", "2007 lan et al.", "lee et al. 2007 .

kdm7a", "al. 2007 .

kdm7a kiaa1718/jhdm1d", ".

kdm7a kiaa1718/jhdm1d catalyses", "kiaa1718/jhdm1d catalyses demethylation of", "demethylation of mono or", "of mono or di", "di methylated lysine 10 of", "methylated lysine 10 of histone", "lysine 10 of histone h3", "of histone h3 h3k9me1/2", "h3 h3k9me1/2 and", "and mono and di", "mono and di methylated", "and di methylated lysine 28", "di methylated lysine 28 of", "of histone h3 h3k27me1/2", "h3k27me1/2 horton et", "et al. 2010 huang", "al. 2010 huang et", "2010 huang et al.", "huang et al. 2010 .", "et al. 2010 . phf8", "2010 . phf8 jhdm1e", "phf8 jhdm1e catalyses", "jhdm1e catalyses demethylation of", "h3k9me1/2 and mono methylated", "and mono methylated lysine 21", "mono methylated lysine 21 of", "methylated lysine 21 of histone", "lysine 21 of histone h4", "of histone h4 h4k20me1", "h4k20me1 loenarz et", "et al. 2010 horton", "al. 2010 horton et", "2010 horton et al.", "et al. 2010 feng", "al. 2010 feng et", "2010 feng et al.", "et al. 2010 kleine", "al. 2010 kleine kohlbrecher", "2010 kleine kohlbrecher et", "kleine kohlbrecher et al. 2010", "et al. 2010 fortschegger", "al. 2010 fortschegger et", "2010 fortschegger et al.", "et al. 2010 qi", "al. 2010 qi et", "2010 qi et al.", "et al. 2010 liu", "al. 2010 liu et", "2010 liu et al.", "liu et al. 2010 .", "et al. 2010 . phf2", "2010 . phf2 jhdm1e", "phf2 jhdm1e catalyses", "h3k9me1/2 wen et", "wen et al 2010", "al 2010 baba", "2010 baba et al.", "baba et al. 2011 .", "et al. 2011 . jmjd6", "al. 2011 . jmjd6 was", "2011 . jmjd6 was initially", ". jmjd6 was initially characterized", "jmjd6 was initially characterized as", "was initially characterized as an", "initially characterized as an arginine", "characterized as an arginine demethylase", "as an arginine demethylase that", "an arginine demethylase that catalyses", "arginine demethylase that catalyses demethylation", "demethylase that catalyses demethylation of", "that catalyses demethylation of mono", "or di methylated arginine 3", "di methylated arginine 3 of", "methylated arginine 3 of histone", "arginine 3 of histone h3", "of histone h3 h3r2me1/2", "h3 h3r2me1/2 and", "h3r2me1/2 and arginine 4", "and arginine 4 of histone", "arginine 4 of histone h4", "of histone h4 h4r3me1/2", "h4r3me1/2 chang et", "et al. 2007 although", "al. 2007 although it", "2007 although it was", "although it was subsequently also", "it was subsequently also characterized", "was subsequently also characterized as", "subsequently also characterized as a", "also characterized as a lysine", "characterized as a lysine hydroxylase", "a lysine hydroxylase webby", "lysine hydroxylase webby et", "hydroxylase webby et al.", "webby et al. 2009 .", "et al. 2009 . n.b.", "al. 2009 . n.b. the", "2009 . n.b. the coordinates", ". n.b. the coordinates of", "n.b. the coordinates of post", "the coordinates of post translational", "when compared with the literature." ] }, { "record_id": "GLY_000594_1_266", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3214847", "r hsa", "hsa 3214847", "r hsa 3214847" ] }, { "record_id": "GLY_000594_1_266", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hats acetylate", "acetylate histones", "hats acetylate histones", "histone acetyltransferases", "involved in", "in histone", "histone modifications", "modifications are", "are referred", "referred to", "to as", "as a", "a type", "type or", "or nuclear", "nuclear hats.", "hats. they", "they can", "can be", "be grouped", "grouped into", "into at", "at least", "least four", "four families", "families based", "based on", "on sequence", "sequence conservation", "conservation within", "within the", "the hat", "hat domain:", "domain: gcn5/pcaf", "p300/cbp and", "and rtt109.", "rtt109. the", "the p300/cbp", "and rtt109", "rtt109 families", "families are", "are specific", "specific to", "to metazoans", "metazoans and", "and fungi", "fungi respectively", "marmorstein &", "& trievel", "trievel 2009", "2009 .", ". gcn5/pcaf", "gcn5/pcaf and", "and myst", "myst family", "family members", "members have", "have no", "no significant", "significant sequence", "sequence homology", "homology but", "but share", "share a", "a globular", "globular alpha/beta", "alpha/beta fold", "fold with", "with a", "a common", "common structure", "structure involved", "in acetyl", "acetyl coenzyme", "coenzyme a", "binding. both", "both use", "use a", "a conserved", "conserved glutamate", "glutamate residue", "residue for", "for the", "the acetyl", "acetyl transfer", "transfer reaction", "reaction but", "but may", "may not", "not share", "common catalytic", "catalytic mechanism", "trievel et", "et al.", "al. 1999", "tanner et", "yan et", "al. 2002", "berndsen et", "al. 2007", "2007 .", ". the", "p300/cbp hat", "hat domain", "domain has", "has no", "no homology", "homology with", "with the", "the other", "other families", "families but", "but some", "some structural", "structural conservation", "within theaca", "theaca binding", "binding core", "liu et", "al. 2008", "2008 .", ". in", "in addition", "addition to", "to histone", "histone acetylation", "members of", "of all", "all 3", "3 human", "human hat", "hat families", "families have", "have been", "been shown", "shown to", "to acetylate", "acetylate non", "non histones", "glozak et", "al. 2005", "2005 .", ".

hats", "

hats and", "and histone", "histone deacetylase", "enzymes generally", "generally act", "act not", "not alone", "alone but", "but as", "as part", "part of", "of multiprotein", "multiprotein complexes.", "complexes. there", "there are", "are numerous", "numerous examples", "examples in", "in which", "which subunits", "subunits of", "of hat", "hat or", "or hdac", "hdac complexes", "complexes influence", "influence their", "their substrate", "substrate specificity", "specificity and", "and lysine", "lysine preference", "which in", "in turn", "affect the", "the broader", "broader functions", "functions of", "of these", "these enzymes", "shahbazian &", "& grunstein", "grunstein 2007", "2007 .

", ".

n.b.", "n.b. the", "the coordinates", "coordinates of", "of post", "post translational", "translational modifications", "modifications represented", "represented and", "and described", "described here", "here follow", "follow uniprot", "uniprot standard", "standard practice", "practice whereby", "whereby coordinates", "coordinates refer", "refer to", "to the", "the translated", "translated protein", "protein before", "before any", "any further", "further processing.", "processing. histone", "histone literature", "literature typically", "typically refers", "refers to", "to coordinates", "of the", "the protein", "protein after", "after the", "the initiating", "initiating methionine", "methionine has", "has been", "been removed.", "removed. therefore", "therefore the", "post translated", "translated residues", "residues in", "in the", "the reactome", "reactome database", "database and", "here are", "are frequently", "frequently +1", "+1 when", "when compared", "compared with", "the literature.", "acetyltransferases hats", "hats involved", "involved in histone", "in histone modifications", "histone modifications are", "modifications are referred", "are referred to", "referred to as", "to as a", "as a type", "a type or", "type or nuclear", "or nuclear hats.", "nuclear hats. they", "hats. they can", "they can be", "can be grouped", "be grouped into", "grouped into at", "into at least", "at least four", "least four families", "four families based", "families based on", "based on sequence", "on sequence conservation", "sequence conservation within", "conservation within the", "within the hat", "the hat domain:", "hat domain: gcn5/pcaf", "gcn5/pcaf myst", "myst p300/cbp", "p300/cbp and rtt109.", "and rtt109. the", "rtt109. the p300/cbp", "the p300/cbp and", "p300/cbp and rtt109", "and rtt109 families", "rtt109 families are", "families are specific", "are specific to", "specific to metazoans", "to metazoans and", "metazoans and fungi", "and fungi respectively", "respectively marmorstein", "marmorstein & trievel", "& trievel 2009", "trievel 2009 .", "2009 . gcn5/pcaf", ". gcn5/pcaf and", "gcn5/pcaf and myst", "and myst family", "myst family members", "family members have", "members have no", "have no significant", "no significant sequence", "significant sequence homology", "sequence homology but", "homology but share", "but share a", "share a globular", "a globular alpha/beta", "globular alpha/beta fold", "alpha/beta fold with", "fold with a", "with a common", "a common structure", "common structure involved", "structure involved in", "involved in acetyl", "in acetyl coenzyme", "acetyl coenzyme a", "a aca", "aca binding.", "binding. both use", "both use a", "use a conserved", "a conserved glutamate", "conserved glutamate residue", "glutamate residue for", "residue for the", "for the acetyl", "the acetyl transfer", "acetyl transfer reaction", "transfer reaction but", "reaction but may", "but may not", "may not share", "not share a", "share a common", "a common catalytic", "common catalytic mechanism", "mechanism trievel", "trievel et al.", "et al. 1999", "1999 tanner", "tanner et al.", "1999 yan", "yan et al.", "et al. 2002", "2002 berndsen", "berndsen et al.", "et al. 2007", "al. 2007 .", "2007 . the", ". the p300/cbp", "the p300/cbp hat", "p300/cbp hat domain", "hat domain has", "domain has no", "has no homology", "no homology with", "homology with the", "with the other", "the other families", "other families but", "families but some", "but some structural", "some structural conservation", "structural conservation within", "conservation within theaca", "within theaca binding", "theaca binding core", "core liu", "liu et al.", "et al. 2008", "al. 2008 .", "2008 . in", ". in addition", "in addition to", "addition to histone", "to histone acetylation", "acetylation members", "members of all", "of all 3", "all 3 human", "3 human hat", "human hat families", "hat families have", "families have been", "have been shown", "been shown to", "shown to acetylate", "to acetylate non", "acetylate non histones", "histones glozak", "glozak et al.", "et al. 2005", "al. 2005 .", "2005 .

hats", ".

hats and", "

hats and histone", "and histone deacetylase", "deacetylase hdac", "hdac enzymes", "enzymes generally act", "generally act not", "act not alone", "not alone but", "alone but as", "but as part", "as part of", "part of multiprotein", "of multiprotein complexes.", "multiprotein complexes. there", "complexes. there are", "there are numerous", "are numerous examples", "numerous examples in", "examples in which", "in which subunits", "which subunits of", "subunits of hat", "of hat or", "hat or hdac", "or hdac complexes", "hdac complexes influence", "complexes influence their", "influence their substrate", "their substrate specificity", "substrate specificity and", "specificity and lysine", "and lysine preference", "preference which", "which in turn", "turn affect", "affect the broader", "the broader functions", "broader functions of", "functions of these", "of these enzymes", "enzymes shahbazian", "shahbazian & grunstein", "& grunstein 2007", "grunstein 2007 .

", "2007 .

n.b.", ".

n.b. the", "n.b. the coordinates", "the coordinates of", "coordinates of post", "of post translational", "post translational modifications", "translational modifications represented", "modifications represented and", "represented and described", "and described here", "described here follow", "here follow uniprot", "follow uniprot standard", "uniprot standard practice", "standard practice whereby", "practice whereby coordinates", "whereby coordinates refer", "coordinates refer to", "refer to the", "to the translated", "the translated protein", "translated protein before", "protein before any", "before any further", "any further processing.", "further processing. histone", "processing. histone literature", "histone literature typically", "literature typically refers", "typically refers to", "refers to coordinates", "to coordinates of", "coordinates of the", "of the protein", "the protein after", "protein after the", "after the initiating", "the initiating methionine", "initiating methionine has", "methionine has been", "has been removed.", "been removed. therefore", "removed. therefore the", "therefore the coordinates", "of post translated", "post translated residues", "translated residues in", "residues in the", "in the reactome", "the reactome database", "reactome database and", "database and described", "described here are", "here are frequently", "are frequently +1", "frequently +1 when", "+1 when compared", "when compared with", "compared with the", "with the literature.", "histone acetyltransferases hats", "hats involved in", "involved in histone modifications", "in histone modifications are", "histone modifications are referred", "modifications are referred to", "are referred to as", "referred to as a", "to as a type", "as a type or", "a type or nuclear", "type or nuclear hats.", "or nuclear hats. they", "nuclear hats. they can", "hats. they can be", "they can be grouped", "can be grouped into", "be grouped into at", "grouped into at least", "into at least four", "at least four families", "least four families based", "four families based on", "families based on sequence", "based on sequence conservation", "on sequence conservation within", "sequence conservation within the", "conservation within the hat", "within the hat domain:", "the hat domain: gcn5/pcaf", "domain: gcn5/pcaf myst", "myst p300/cbp and", "p300/cbp and rtt109. the", "and rtt109. the p300/cbp", "rtt109. the p300/cbp and", "the p300/cbp and rtt109", "p300/cbp and rtt109 families", "and rtt109 families are", "rtt109 families are specific", "families are specific to", "are specific to metazoans", "specific to metazoans and", "to metazoans and fungi", "metazoans and fungi respectively", "fungi respectively marmorstein", "respectively marmorstein &", "marmorstein & trievel 2009", "& trievel 2009 .", "trievel 2009 . gcn5/pcaf", "2009 . gcn5/pcaf and", ". gcn5/pcaf and myst", "gcn5/pcaf and myst family", "and myst family members", "myst family members have", "family members have no", "members have no significant", "have no significant sequence", "no significant sequence homology", "significant sequence homology but", "sequence homology but share", "homology but share a", "but share a globular", "share a globular alpha/beta", "a globular alpha/beta fold", "globular alpha/beta fold with", "alpha/beta fold with a", "fold with a common", "with a common structure", "a common structure involved", "common structure involved in", "structure involved in acetyl", "involved in acetyl coenzyme", "in acetyl coenzyme a", "coenzyme a aca", "aca binding. both", "binding. both use a", "both use a conserved", "use a conserved glutamate", "a conserved glutamate residue", "conserved glutamate residue for", "glutamate residue for the", "residue for the acetyl", "for the acetyl transfer", "the acetyl transfer reaction", "acetyl transfer reaction but", "transfer reaction but may", "reaction but may not", "but may not share", "may not share a", "not share a common", "share a common catalytic", "a common catalytic mechanism", "catalytic mechanism trievel", "mechanism trievel et", "trievel et al. 1999", "al. 1999 tanner", "1999 tanner et", "tanner et al. 1999", "al. 1999 yan", "1999 yan et", "yan et al. 2002", "al. 2002 berndsen", "2002 berndsen et", "berndsen et al. 2007", "et al. 2007 .", "al. 2007 . the", "2007 . the p300/cbp", ". the p300/cbp hat", "the p300/cbp hat domain", "p300/cbp hat domain has", "hat domain has no", "domain has no homology", "has no homology with", "no homology with the", "homology with the other", "with the other families", "the other families but", "other families but some", "families but some structural", "but some structural conservation", "some structural conservation within", "structural conservation within theaca", "conservation within theaca binding", "within theaca binding core", "binding core liu", "core liu et", "liu et al. 2008", "et al. 2008 .", "al. 2008 . in", "2008 . in addition", ". in addition to", "in addition to histone", "addition to histone acetylation", "histone acetylation members", "acetylation members of", "members of all 3", "of all 3 human", "all 3 human hat", "3 human hat families", "human hat families have", "hat families have been", "families have been shown", "have been shown to", "been shown to acetylate", "shown to acetylate non", "to acetylate non histones", "non histones glozak", "histones glozak et", "glozak et al. 2005", "et al. 2005 .", "al. 2005 .

hats", "2005 .

hats and", ".

hats and histone", "

hats and histone deacetylase", "histone deacetylase hdac", "hdac enzymes generally", "enzymes generally act not", "generally act not alone", "act not alone but", "not alone but as", "alone but as part", "but as part of", "as part of multiprotein", "part of multiprotein complexes.", "of multiprotein complexes. there", "multiprotein complexes. there are", "complexes. there are numerous", "there are numerous examples", "are numerous examples in", "numerous examples in which", "examples in which subunits", "in which subunits of", "which subunits of hat", "subunits of hat or", "of hat or hdac", "hat or hdac complexes", "or hdac complexes influence", "hdac complexes influence their", "complexes influence their substrate", "influence their substrate specificity", "their substrate specificity and", "substrate specificity and lysine", "specificity and lysine preference", "lysine preference which", "preference which in", "in turn affect", "turn affect the", "affect the broader functions", "the broader functions of", "broader functions of these", "functions of these enzymes", "these enzymes shahbazian", "enzymes shahbazian &", "shahbazian & grunstein 2007", "& grunstein 2007 .

", "grunstein 2007 .

n.b.", "2007 .

n.b. the", ".

n.b. the coordinates", "n.b. the coordinates of", "the coordinates of post", "coordinates of post translational", "of post translational modifications", "post translational modifications represented", "translational modifications represented and", "modifications represented and described", "represented and described here", "and described here follow", "described here follow uniprot", "here follow uniprot standard", "follow uniprot standard practice", "uniprot standard practice whereby", "standard practice whereby coordinates", "practice whereby coordinates refer", "whereby coordinates refer to", "coordinates refer to the", "refer to the translated", "to the translated protein", "the translated protein before", "translated protein before any", "protein before any further", "before any further processing.", "any further processing. histone", "further processing. histone literature", "processing. histone literature typically", "histone literature typically refers", "literature typically refers to", "typically refers to coordinates", "refers to coordinates of", "to coordinates of the", "coordinates of the protein", "of the protein after", "the protein after the", "protein after the initiating", "after the initiating methionine", "the initiating methionine has", "initiating methionine has been", "methionine has been removed.", "has been removed. therefore", "been removed. therefore the", "removed. therefore the coordinates", "therefore the coordinates of", "coordinates of post translated", "of post translated residues", "post translated residues in", "translated residues in the", "residues in the reactome", "in the reactome database", "the reactome database and", "reactome database and described", "database and described here", "and described here are", "described here are frequently", "here are frequently +1", "are frequently +1 when", "frequently +1 when compared", "+1 when compared with", "when compared with the", "compared with the literature.", "acetyltransferases hats involved", "hats involved in histone", "involved in histone modifications are", "in histone modifications are referred", "histone modifications are referred to", "modifications are referred to as", "are referred to as a", "referred to as a type", "to as a type or", "as a type or nuclear", "a type or nuclear hats.", "type or nuclear hats. they", "or nuclear hats. they can", "nuclear hats. they can be", "hats. they can be grouped", "they can be grouped into", "can be grouped into at", "be grouped into at least", "grouped into at least four", "into at least four families", "at least four families based", "least four families based on", "four families based on sequence", "families based on sequence conservation", "based on sequence conservation within", "on sequence conservation within the", "sequence conservation within the hat", "conservation within the hat domain:", "within the hat domain: gcn5/pcaf", "hat domain: gcn5/pcaf myst", "gcn5/pcaf myst p300/cbp", "myst p300/cbp and rtt109.", "p300/cbp and rtt109. the p300/cbp", "and rtt109. the p300/cbp and", "rtt109. the p300/cbp and rtt109", "the p300/cbp and rtt109 families", "p300/cbp and rtt109 families are", "and rtt109 families are specific", "rtt109 families are specific to", "families are specific to metazoans", "are specific to metazoans and", "specific to metazoans and fungi", "to metazoans and fungi respectively", "and fungi respectively marmorstein", "fungi respectively marmorstein &", "respectively marmorstein & trievel", "marmorstein & trievel 2009 .", "& trievel 2009 . gcn5/pcaf", "trievel 2009 . gcn5/pcaf and", "2009 . gcn5/pcaf and myst", ". gcn5/pcaf and myst family", "gcn5/pcaf and myst family members", "and myst family members have", "myst family members have no", "family members have no significant", "members have no significant sequence", "have no significant sequence homology", "no significant sequence homology but", "significant sequence homology but share", "sequence homology but share a", "homology but share a globular", "but share a globular alpha/beta", "share a globular alpha/beta fold", "a globular alpha/beta fold with", "globular alpha/beta fold with a", "alpha/beta fold with a common", "fold with a common structure", "with a common structure involved", "a common structure involved in", "common structure involved in acetyl", "structure involved in acetyl coenzyme", "involved in acetyl coenzyme a", "acetyl coenzyme a aca", "a aca binding.", "aca binding. both use", "binding. both use a conserved", "both use a conserved glutamate", "use a conserved glutamate residue", "a conserved glutamate residue for", "conserved glutamate residue for the", "glutamate residue for the acetyl", "residue for the acetyl transfer", "for the acetyl transfer reaction", "the acetyl transfer reaction but", "acetyl transfer reaction but may", "transfer reaction but may not", "reaction but may not share", "but may not share a", "may not share a common", "not share a common catalytic", "share a common catalytic mechanism", "common catalytic mechanism trievel", "catalytic mechanism trievel et", "mechanism trievel et al.", "et al. 1999 tanner", "al. 1999 tanner et", "1999 tanner et al.", "et al. 1999 yan", "al. 1999 yan et", "1999 yan et al.", "et al. 2002 berndsen", "al. 2002 berndsen et", "2002 berndsen et al.", "berndsen et al. 2007 .", "et al. 2007 . the", "al. 2007 . the p300/cbp", "2007 . the p300/cbp hat", ". the p300/cbp hat domain", "the p300/cbp hat domain has", "p300/cbp hat domain has no", "hat domain has no homology", "domain has no homology with", "has no homology with the", "no homology with the other", "homology with the other families", "with the other families but", "the other families but some", "other families but some structural", "families but some structural conservation", "but some structural conservation within", "some structural conservation within theaca", "structural conservation within theaca binding", "conservation within theaca binding core", "theaca binding core liu", "binding core liu et", "core liu et al.", "liu et al. 2008 .", "et al. 2008 . in", "al. 2008 . in addition", "2008 . in addition to", ". in addition to histone", "in addition to histone acetylation", "to histone acetylation members", "histone acetylation members of", "acetylation members of all", "members of all 3 human", "of all 3 human hat", "all 3 human hat families", "3 human hat families have", "human hat families have been", "hat families have been shown", "families have been shown to", "have been shown to acetylate", "been shown to acetylate non", "shown to acetylate non histones", "acetylate non histones glozak", "non histones glozak et", "histones glozak et al.", "glozak et al. 2005 .", "et al. 2005 .

hats", "al. 2005 .

hats and", "2005 .

hats and histone", ".

hats and histone deacetylase", "and histone deacetylase hdac", "deacetylase hdac enzymes", "hdac enzymes generally act", "enzymes generally act not alone", "generally act not alone but", "act not alone but as", "not alone but as part", "alone but as part of", "but as part of multiprotein", "as part of multiprotein complexes.", "part of multiprotein complexes. there", "of multiprotein complexes. there are", "multiprotein complexes. there are numerous", "complexes. there are numerous examples", "there are numerous examples in", "are numerous examples in which", "numerous examples in which subunits", "examples in which subunits of", "in which subunits of hat", "which subunits of hat or", "subunits of hat or hdac", "of hat or hdac complexes", "hat or hdac complexes influence", "or hdac complexes influence their", "hdac complexes influence their substrate", "complexes influence their substrate specificity", "influence their substrate specificity and", "their substrate specificity and lysine", "substrate specificity and lysine preference", "and lysine preference which", "lysine preference which in", "preference which in turn", "which in turn affect", "in turn affect the", "turn affect the broader", "affect the broader functions of", "the broader functions of these", "broader functions of these enzymes", "of these enzymes shahbazian", "these enzymes shahbazian &", "enzymes shahbazian & grunstein", "shahbazian & grunstein 2007 .

", "& grunstein 2007 .

n.b.", "grunstein 2007 .

n.b. the", "2007 .

n.b. the coordinates", ".

n.b. the coordinates of", "n.b. the coordinates of post", "the coordinates of post translational", "coordinates of post translational modifications", "of post translational modifications represented", "post translational modifications represented and", "translational modifications represented and described", "modifications represented and described here", "represented and described here follow", "and described here follow uniprot", "described here follow uniprot standard", "here follow uniprot standard practice", "follow uniprot standard practice whereby", "uniprot standard practice whereby coordinates", "standard practice whereby coordinates refer", "practice whereby coordinates refer to", "whereby coordinates refer to the", "coordinates refer to the translated", "refer to the translated protein", "to the translated protein before", "the translated protein before any", "translated protein before any further", "protein before any further processing.", "before any further processing. histone", "any further processing. histone literature", "further processing. histone literature typically", "processing. histone literature typically refers", "histone literature typically refers to", "literature typically refers to coordinates", "typically refers to coordinates of", "refers to coordinates of the", "to coordinates of the protein", "coordinates of the protein after", "of the protein after the", "the protein after the initiating", "protein after the initiating methionine", "after the initiating methionine has", "the initiating methionine has been", "initiating methionine has been removed.", "methionine has been removed. therefore", "has been removed. therefore the", "been removed. therefore the coordinates", "removed. therefore the coordinates of", "therefore the coordinates of post", "the coordinates of post translated", "coordinates of post translated residues", "of post translated residues in", "post translated residues in the", "translated residues in the reactome", "residues in the reactome database", "in the reactome database and", "the reactome database and described", "reactome database and described here", "database and described here are", "and described here are frequently", "described here are frequently +1", "here are frequently +1 when", "are frequently +1 when compared", "frequently +1 when compared with", "+1 when compared with the", "when compared with the literature." ] }, { "record_id": "GLY_000594_1_267", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3214858", "r hsa", "hsa 3214858", "r hsa 3214858" ] }, { "record_id": "GLY_000594_1_267", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rmts methylate", "methylate histone", "histone arginines", "rmts methylate histone", "methylate histone arginines", "rmts methylate histone arginines", "arginine methylation", "methylation is", "is a", "a common", "common post", "post translational", "translational modification", "around 2%", "2% of", "of arginine", "arginine residues", "residues are", "are methylated", "methylated in", "in rat", "rat liver", "liver nuclei", "boffa et", "et al.", "al. 1977", "1977 .", ". arginine", "arginine can", "can be", "be methylated", "in 3", "3 different", "different ways:", "ways: monomethylarginine", "ng ng", "ng asymmetric", "asymmetric dimethylarginine", "and ng", "ng n'g", "n'g symmetric", "symmetric dimethylarginine", "sdma .", ". the", "the formation", "formation of", "of mma", "adma and", "and sdma", "sdma in", "in mammalian", "mammalian cells", "cells is", "is carried", "carried out", "out by", "by members", "members of", "of a", "a family", "family of", "of nine", "nine protein", "protein arginine", "arginine methyltransferases", "bedford &", "& clarke", "clarke 2009", "2009 .", ".

type", "

type i", "ii and", "and iii", "iii prmts", "prmts generate", "generate mma", "mma on", "on one", "one of", "of the", "the two", "two terminal", "guanidino nitrogen", "nitrogen atoms.", "atoms. subsequent", "subsequent generation", "generation of", "of asymmetric", "is catalysed", "catalysed by", "by the", "the type", "type i", "i enzymes", "enzymes prmt1", "co activator", "activator associated", "associated arginine", "arginine methyltransferase", "methyltransferase 1", "prmt6 and", "and prmt8.", "prmt8. production", "production of", "of symmetric", "type ii", "ii enzymes", "enzymes prmt5", "prmt5 and", "and prmt7.", "prmt7. on", "on certain", "certain substrates", "prmt7 also", "also functions", "functions as", "as a", "a type", "type iii", "iii enzyme", "generating mma", "mma only.", "only. prmt9", "prmt9 activity", "activity has", "has not", "not been", "been characterized.", "characterized. no", "no known", "known enzyme", "enzyme is", "is capable", "capable of", "of both", "both adma", "sdma modifications.", "modifications. arginine", "is regarded", "regarded as", "as highly", "highly stable", "no arginine", "arginine demethylases", "demethylases are", "are known", "yang &", "& bedford", "bedford 2013", "2013 .", ".

most", "

most prmts", "prmts methylate", "methylate glycine", "and arginine", "arginine rich", "motifs in", "in their", "their substrates", ". carm1", "carm1 methylates", "methylates a", "a proline", "and methionine", "methionine rich", "cheng et", "al. 2007", "2007 .", ". prmt5", "prmt5 can", "can dimethylate", "dimethylate arginine", "residues in", "in gar", "gar and", "and pgm", "pgm motifs", "branscombe et", "al. 2001", "2001 .", ".

prmts", "

prmts are", "are widely", "widely expressed", "expressed and", "and are", "are constitutively", "constitutively active", "active as", "as purified", "purified recombinant", "recombinant proteins.", "proteins. however", "prmt activity", "activity can", "be regulated", "regulated through", "through ptms", "association with", "with regulatory", "regulatory proteins", "subcellular compartmentalization", "compartmentalization and", "and factors", "factors that", "that affect", "affect enzyme", "enzyme substrate", "substrate interactions.", "interactions. the", "the target", "target sites", "sites of", "of prmts", "prmts are", "are influenced", "influenced by", "the presence", "presence of", "of other", "other ptms", "ptms on", "on their", "their substrates.", "substrates. the", "the best", "best characterized", "characterized examples", "examples of", "of this", "this are", "are for", "for histones.", "histones. histone", "histone h3", "h3 lysine", "lysine 19", "19 acetylation", "primes the", "the histone", "histone tail", "tail for", "for asymmetric", "asymmetric dimethylation", "dimethylation at", "at arginine", "arginine 18", "by carm1", "an et", "al. 2003", "daujat et", "al. 2002", "yue et", ". h3", "lysine 10", "10 acetylation", "blocks arginine", "arginine 9", "9 symmetric", "symmetric dimethylation", "by prmt5", "pal et", "al. 2004", "2004 .", ". h4r3me2a", "h4r3me2a catalyzed", "catalyzed by", "by prmt1", "prmt1 favours", "favours subsequent", "subsequent acetylation", "acetylation of", "histone h4", "h4 tail", "huang et", "al. 2005", "2005 .", ". at", "at the", "the same", "same time", "time histone", "h4 lysine", "lysine 5", "5 acetylation", "makes the", "the h4r3", "h4r3 motif", "motif a", "a better", "better substrate", "substrate for", "for prmt5", "prmt5 compared", "compared with", "with prmt1", "thereby moving", "moving the", "the balance", "balance from", "from an", "an activating", "activating adma", "adma mark", "mark to", "to a", "a suppressive", "suppressive sdma", "sdma mark", "mark at", "feng et", "al. 2011", "2011 .", ". finally", "finally methylation", "methylation of", "of histone", "h3 on", "on arginine", "arginine 3", "by prmt6", "prmt6 blocks", "blocks methylation", "of h3", "5 by", "the mll", "mll complex", "and vice", "vice versa", "of h3k4me3", "h3k4me3 prevents", "prevents h3r2me2a", "h3r2me2a methylation", "guccione et", "kirmizis et", "hyllus et", ". n.b.", "n.b. the", "the coordinates", "coordinates of", "of post", "translational modifications", "modifications represented", "represented and", "and described", "described here", "here follow", "follow uniprot", "uniprot standard", "standard practice", "practice whereby", "whereby coordinates", "coordinates refer", "refer to", "to the", "the translated", "translated protein", "protein before", "before any", "any further", "further processing.", "processing. histone", "histone literature", "literature typically", "typically refers", "refers to", "to coordinates", "the protein", "protein after", "after the", "the initiating", "initiating methionine", "methionine has", "has been", "been removed.", "removed. therefore", "therefore the", "post translated", "translated residues", "in the", "the reactome", "reactome database", "database and", "here are", "are frequently", "frequently +1", "+1 when", "when compared", "with the", "the literature.", "arginine methylation is", "methylation is a", "is a common", "a common post", "common post translational", "post translational modification", "modification around", "around 2% of", "2% of arginine", "of arginine residues", "arginine residues are", "residues are methylated", "are methylated in", "methylated in rat", "in rat liver", "rat liver nuclei", "nuclei boffa", "boffa et al.", "et al. 1977", "al. 1977 .", "1977 . arginine", ". arginine can", "arginine can be", "can be methylated", "be methylated in", "methylated in 3", "in 3 different", "3 different ways:", "different ways: monomethylarginine", "monomethylarginine mma", "ng ng asymmetric", "ng asymmetric dimethylarginine", "dimethylarginine adma", "and ng n'g", "ng n'g symmetric", "n'g symmetric dimethylarginine", "dimethylarginine sdma", "sdma . the", ". the formation", "the formation of", "formation of mma", "mma adma", "adma and sdma", "and sdma in", "sdma in mammalian", "in mammalian cells", "mammalian cells is", "cells is carried", "is carried out", "carried out by", "out by members", "by members of", "members of a", "of a family", "a family of", "family of nine", "of nine protein", "nine protein arginine", "protein arginine methyltransferases", "methyltransferases prmts", "bedford & clarke", "& clarke 2009", "clarke 2009 .", "2009 .

type", ".

type i", "i ii", "ii and iii", "and iii prmts", "iii prmts generate", "prmts generate mma", "generate mma on", "mma on one", "on one of", "one of the", "of the two", "the two terminal", "terminal guanidino", "guanidino nitrogen atoms.", "nitrogen atoms. subsequent", "atoms. subsequent generation", "subsequent generation of", "generation of asymmetric", "of asymmetric dimethylarginine", "adma is", "is catalysed by", "catalysed by the", "by the type", "the type i", "type i enzymes", "i enzymes prmt1", "prmt1 prmt2", "prmt2 prmt3", "prmt3 co", "co activator associated", "activator associated arginine", "associated arginine methyltransferase", "arginine methyltransferase 1", "1 carm1", "prmt6 and prmt8.", "and prmt8. production", "prmt8. production of", "production of symmetric", "of symmetric dimethylarginine", "sdma is", "the type ii", "type ii enzymes", "ii enzymes prmt5", "enzymes prmt5 and", "prmt5 and prmt7.", "and prmt7. on", "prmt7. on certain", "on certain substrates", "substrates prmt7", "prmt7 also functions", "also functions as", "functions as a", "as a type", "a type iii", "type iii enzyme", "enzyme generating", "generating mma only.", "mma only. prmt9", "only. prmt9 activity", "prmt9 activity has", "activity has not", "has not been", "not been characterized.", "been characterized. no", "characterized. no known", "no known enzyme", "known enzyme is", "enzyme is capable", "is capable of", "capable of both", "of both adma", "both adma and", "and sdma modifications.", "sdma modifications. arginine", "modifications. arginine methylation", "methylation is regarded", "is regarded as", "regarded as highly", "as highly stable", "stable no", "no arginine demethylases", "arginine demethylases are", "demethylases are known", "known yang", "yang & bedford", "& bedford 2013", "bedford 2013 .", "2013 .

most", ".

most prmts", "

most prmts methylate", "prmts methylate glycine", "glycine and", "and arginine rich", "rich gar", "gar motifs", "motifs in their", "in their substrates", "substrates boffa", "1977 . carm1", ". carm1 methylates", "carm1 methylates a", "methylates a proline", "and methionine rich", "rich pgm", "pgm motif", "motif cheng", "cheng et al.", "et al. 2007", "al. 2007 .", "2007 . prmt5", ". prmt5 can", "prmt5 can dimethylate", "can dimethylate arginine", "dimethylate arginine residues", "arginine residues in", "residues in gar", "in gar and", "gar and pgm", "and pgm motifs", "motifs cheng", "2007 branscombe", "branscombe et al.", "et al. 2001", "al. 2001 .", "2001 .

prmts", ".

prmts are", "

prmts are widely", "are widely expressed", "widely expressed and", "expressed and are", "and are constitutively", "are constitutively active", "constitutively active as", "active as purified", "as purified recombinant", "purified recombinant proteins.", "recombinant proteins. however", "however prmt", "prmt activity can", "activity can be", "can be regulated", "be regulated through", "regulated through ptms", "ptms association", "association with regulatory", "with regulatory proteins", "proteins subcellular", "subcellular compartmentalization and", "compartmentalization and factors", "and factors that", "factors that affect", "that affect enzyme", "affect enzyme substrate", "enzyme substrate interactions.", "substrate interactions. the", "interactions. the target", "the target sites", "target sites of", "sites of prmts", "of prmts are", "prmts are influenced", "are influenced by", "influenced by the", "by the presence", "the presence of", "presence of other", "of other ptms", "other ptms on", "ptms on their", "on their substrates.", "their substrates. the", "substrates. the best", "the best characterized", "best characterized examples", "characterized examples of", "examples of this", "of this are", "this are for", "are for histones.", "for histones. histone", "histones. histone h3", "histone h3 lysine", "h3 lysine 19", "lysine 19 acetylation", "acetylation h3k18ac", "h3k18ac primes", "primes the histone", "the histone tail", "histone tail for", "tail for asymmetric", "for asymmetric dimethylation", "asymmetric dimethylation at", "dimethylation at arginine", "at arginine 18", "18 h3r17me2a", "h3r17me2a by", "carm1 an", "an et al.", "et al. 2003", "2003 daujat", "daujat et al.", "et al. 2002", "2002 yue", "yue et al.", "2007 . h3", ". h3 lysine", "h3 lysine 10", "lysine 10 acetylation", "acetylation h3k9ac", "h3k9ac blocks", "blocks arginine 9", "arginine 9 symmetric", "9 symmetric dimethylation", "dimethylation h3r8me2s", "h3r8me2s by", "prmt5 pal", "pal et al.", "et al. 2004", "al. 2004 .", "2004 . h4r3me2a", ". h4r3me2a catalyzed", "h4r3me2a catalyzed by", "catalyzed by prmt1", "by prmt1 favours", "prmt1 favours subsequent", "favours subsequent acetylation", "subsequent acetylation of", "acetylation of the", "of the histone", "the histone h4", "histone h4 tail", "tail huang", "huang et al.", "et al. 2005", "al. 2005 .", "2005 . at", ". at the", "at the same", "the same time", "same time histone", "time histone h4", "histone h4 lysine", "h4 lysine 5", "lysine 5 acetylation", "acetylation h4k5ac", "h4k5ac makes", "makes the h4r3", "the h4r3 motif", "h4r3 motif a", "motif a better", "a better substrate", "better substrate for", "substrate for prmt5", "for prmt5 compared", "prmt5 compared with", "compared with prmt1", "prmt1 thereby", "thereby moving the", "moving the balance", "the balance from", "balance from an", "from an activating", "an activating adma", "activating adma mark", "adma mark to", "mark to a", "to a suppressive", "a suppressive sdma", "suppressive sdma mark", "sdma mark at", "mark at the", "at the h4r3", "motif feng", "feng et al.", "et al. 2011", "al. 2011 .", "2011 . finally", ". finally methylation", "finally methylation of", "methylation of histone", "of histone h3", "histone h3 on", "h3 on arginine", "on arginine 3", "3 h3r2me2a", "h3r2me2a by", "by prmt6 blocks", "prmt6 blocks methylation", "blocks methylation of", "methylation of h3", "of h3 lysine", "h3 lysine 5", "lysine 5 by", "5 by the", "by the mll", "the mll complex", "complex h3k4me3", "and vice versa", "versa methylation", "methylation of h3k4me3", "of h3k4me3 prevents", "h3k4me3 prevents h3r2me2a", "prevents h3r2me2a methylation", "methylation guccione", "guccione et al.", "2007 kirmizis", "kirmizis et al.", "2007 hyllus", "hyllus et al.", "2007 . n.b.", ". n.b. the", "n.b. the coordinates", "the coordinates of", "coordinates of post", "of post translational", "post translational modifications", "translational modifications represented", "modifications represented and", "represented and described", "and described here", "described here follow", "here follow uniprot", "follow uniprot standard", "uniprot standard practice", "standard practice whereby", "practice whereby coordinates", "whereby coordinates refer", "coordinates refer to", "refer to the", "to the translated", "the translated protein", "translated protein before", "protein before any", "before any further", "any further processing.", "further processing. histone", "processing. histone literature", "histone literature typically", "literature typically refers", "typically refers to", "refers to coordinates", "to coordinates of", "coordinates of the", "of the protein", "the protein after", "protein after the", "after the initiating", "the initiating methionine", "initiating methionine has", "methionine has been", "has been removed.", "been removed. therefore", "removed. therefore the", "therefore the coordinates", "of post translated", "post translated residues", "translated residues in", "residues in the", "in the reactome", "the reactome database", "reactome database and", "database and described", "described here are", "here are frequently", "are frequently +1", "frequently +1 when", "+1 when compared", "when compared with", "compared with the", "with the literature.", "arginine methylation is a", "methylation is a common", "is a common post", "a common post translational", "common post translational modification", "translational modification around", "modification around 2%", "around 2% of arginine", "2% of arginine residues", "of arginine residues are", "arginine residues are methylated", "residues are methylated in", "are methylated in rat", "methylated in rat liver", "in rat liver nuclei", "liver nuclei boffa", "nuclei boffa et", "boffa et al. 1977", "et al. 1977 .", "al. 1977 . arginine", "1977 . arginine can", ". arginine can be", "arginine can be methylated", "can be methylated in", "be methylated in 3", "methylated in 3 different", "in 3 different ways:", "3 different ways: monomethylarginine", "ways: monomethylarginine mma", "mma ng", "ng ng asymmetric dimethylarginine", "asymmetric dimethylarginine adma", "adma and ng", "and ng n'g symmetric", "ng n'g symmetric dimethylarginine", "symmetric dimethylarginine sdma", "dimethylarginine sdma .", "sdma . the formation", ". the formation of", "the formation of mma", "of mma adma", "mma adma and", "adma and sdma in", "and sdma in mammalian", "sdma in mammalian cells", "in mammalian cells is", "mammalian cells is carried", "cells is carried out", "is carried out by", "carried out by members", "out by members of", "by members of a", "members of a family", "of a family of", "a family of nine", "family of nine protein", "of nine protein arginine", "nine protein arginine methyltransferases", "arginine methyltransferases prmts", "prmts bedford", "bedford & clarke 2009", "& clarke 2009 .", "clarke 2009 .

type", "2009 .

type i", "

type i ii", "i ii and", "ii and iii prmts", "and iii prmts generate", "iii prmts generate mma", "prmts generate mma on", "generate mma on one", "mma on one of", "on one of the", "one of the two", "of the two terminal", "two terminal guanidino", "terminal guanidino nitrogen", "guanidino nitrogen atoms. subsequent", "nitrogen atoms. subsequent generation", "atoms. subsequent generation of", "subsequent generation of asymmetric", "generation of asymmetric dimethylarginine", "adma is catalysed", "is catalysed by the", "catalysed by the type", "by the type i", "the type i enzymes", "type i enzymes prmt1", "enzymes prmt1 prmt2", "prmt3 co activator", "co activator associated arginine", "activator associated arginine methyltransferase", "associated arginine methyltransferase 1", "methyltransferase 1 carm1", "carm1 prmt6", "prmt6 and prmt8. production", "and prmt8. production of", "prmt8. production of symmetric", "production of symmetric dimethylarginine", "sdma is catalysed", "by the type ii", "the type ii enzymes", "type ii enzymes prmt5", "ii enzymes prmt5 and", "enzymes prmt5 and prmt7.", "prmt5 and prmt7. on", "and prmt7. on certain", "prmt7. on certain substrates", "certain substrates prmt7", "substrates prmt7 also", "prmt7 also functions as", "also functions as a", "functions as a type", "as a type iii", "a type iii enzyme", "iii enzyme generating", "enzyme generating mma", "generating mma only. prmt9", "mma only. prmt9 activity", "only. prmt9 activity has", "prmt9 activity has not", "activity has not been", "has not been characterized.", "not been characterized. no", "been characterized. no known", "characterized. no known enzyme", "no known enzyme is", "known enzyme is capable", "enzyme is capable of", "is capable of both", "capable of both adma", "of both adma and", "both adma and sdma", "adma and sdma modifications.", "and sdma modifications. arginine", "sdma modifications. arginine methylation", "modifications. arginine methylation is", "arginine methylation is regarded", "methylation is regarded as", "is regarded as highly", "regarded as highly stable", "highly stable no", "stable no arginine", "no arginine demethylases are", "arginine demethylases are known", "are known yang", "known yang &", "yang & bedford 2013", "& bedford 2013 .", "bedford 2013 .

most", "2013 .

most prmts", ".

most prmts methylate", "

most prmts methylate glycine", "methylate glycine and", "glycine and arginine", "arginine rich gar", "gar motifs in", "motifs in their substrates", "their substrates boffa", "substrates boffa et", "al. 1977 . carm1", "1977 . carm1 methylates", ". carm1 methylates a", "carm1 methylates a proline", "proline glycine", "glycine and methionine", "methionine rich pgm", "motif cheng et", "cheng et al. 2007", "et al. 2007 .", "al. 2007 . prmt5", "2007 . prmt5 can", ". prmt5 can dimethylate", "prmt5 can dimethylate arginine", "can dimethylate arginine residues", "dimethylate arginine residues in", "arginine residues in gar", "residues in gar and", "in gar and pgm", "gar and pgm motifs", "pgm motifs cheng", "motifs cheng et", "al. 2007 branscombe", "2007 branscombe et", "branscombe et al. 2001", "et al. 2001 .", "al. 2001 .

prmts", "2001 .

prmts are", ".

prmts are widely", "

prmts are widely expressed", "are widely expressed and", "widely expressed and are", "expressed and are constitutively", "and are constitutively active", "are constitutively active as", "constitutively active as purified", "active as purified recombinant", "as purified recombinant proteins.", "purified recombinant proteins. however", "proteins. however prmt", "however prmt activity", "prmt activity can be", "activity can be regulated", "can be regulated through", "be regulated through ptms", "through ptms association", "ptms association with", "association with regulatory proteins", "regulatory proteins subcellular", "proteins subcellular compartmentalization", "subcellular compartmentalization and factors", "compartmentalization and factors that", "and factors that affect", "factors that affect enzyme", "that affect enzyme substrate", "affect enzyme substrate interactions.", "enzyme substrate interactions. the", "substrate interactions. the target", "interactions. the target sites", "the target sites of", "target sites of prmts", "sites of prmts are", "of prmts are influenced", "prmts are influenced by", "are influenced by the", "influenced by the presence", "by the presence of", "the presence of other", "presence of other ptms", "of other ptms on", "other ptms on their", "ptms on their substrates.", "on their substrates. the", "their substrates. the best", "substrates. the best characterized", "the best characterized examples", "best characterized examples of", "characterized examples of this", "examples of this are", "of this are for", "this are for histones.", "are for histones. histone", "for histones. histone h3", "histones. histone h3 lysine", "histone h3 lysine 19", "h3 lysine 19 acetylation", "19 acetylation h3k18ac", "h3k18ac primes the", "primes the histone tail", "the histone tail for", "histone tail for asymmetric", "tail for asymmetric dimethylation", "for asymmetric dimethylation at", "asymmetric dimethylation at arginine", "dimethylation at arginine 18", "arginine 18 h3r17me2a", "h3r17me2a by carm1", "by carm1 an", "carm1 an et", "an et al. 2003", "al. 2003 daujat", "2003 daujat et", "daujat et al. 2002", "al. 2002 yue", "2002 yue et", "yue et al. 2007", "al. 2007 . h3", "2007 . h3 lysine", ". h3 lysine 10", "h3 lysine 10 acetylation", "10 acetylation h3k9ac", "h3k9ac blocks arginine", "blocks arginine 9 symmetric", "arginine 9 symmetric dimethylation", "symmetric dimethylation h3r8me2s", "h3r8me2s by prmt5", "by prmt5 pal", "prmt5 pal et", "pal et al. 2004", "et al. 2004 .", "al. 2004 . h4r3me2a", "2004 . h4r3me2a catalyzed", ". h4r3me2a catalyzed by", "h4r3me2a catalyzed by prmt1", "catalyzed by prmt1 favours", "by prmt1 favours subsequent", "prmt1 favours subsequent acetylation", "favours subsequent acetylation of", "subsequent acetylation of the", "acetylation of the histone", "of the histone h4", "the histone h4 tail", "h4 tail huang", "tail huang et", "huang et al. 2005", "et al. 2005 .", "al. 2005 . at", "2005 . at the", ". at the same", "at the same time", "the same time histone", "same time histone h4", "time histone h4 lysine", "histone h4 lysine 5", "h4 lysine 5 acetylation", "5 acetylation h4k5ac", "h4k5ac makes the", "makes the h4r3 motif", "the h4r3 motif a", "h4r3 motif a better", "motif a better substrate", "a better substrate for", "better substrate for prmt5", "substrate for prmt5 compared", "for prmt5 compared with", "prmt5 compared with prmt1", "with prmt1 thereby", "prmt1 thereby moving", "thereby moving the balance", "moving the balance from", "the balance from an", "balance from an activating", "from an activating adma", "an activating adma mark", "activating adma mark to", "adma mark to a", "mark to a suppressive", "to a suppressive sdma", "a suppressive sdma mark", "suppressive sdma mark at", "sdma mark at the", "mark at the h4r3", "at the h4r3 motif", "h4r3 motif feng", "motif feng et", "feng et al. 2011", "et al. 2011 .", "al. 2011 . finally", "2011 . finally methylation", ". finally methylation of", "finally methylation of histone", "methylation of histone h3", "of histone h3 on", "histone h3 on arginine", "h3 on arginine 3", "arginine 3 h3r2me2a", "h3r2me2a by prmt6", "by prmt6 blocks methylation", "prmt6 blocks methylation of", "blocks methylation of h3", "methylation of h3 lysine", "of h3 lysine 5", "h3 lysine 5 by", "lysine 5 by the", "5 by the mll", "by the mll complex", "mll complex h3k4me3", "h3k4me3 and", "vice versa methylation", "versa methylation of", "methylation of h3k4me3 prevents", "of h3k4me3 prevents h3r2me2a", "h3k4me3 prevents h3r2me2a methylation", "h3r2me2a methylation guccione", "methylation guccione et", "guccione et al. 2007", "al. 2007 kirmizis", "2007 kirmizis et", "kirmizis et al. 2007", "al. 2007 hyllus", "2007 hyllus et", "hyllus et al. 2007", "al. 2007 . n.b.", "2007 . n.b. the", ". n.b. the coordinates", "n.b. the coordinates of", "the coordinates of post", "coordinates of post translational", "of post translational modifications", "post translational modifications represented", "translational modifications represented and", "modifications represented and described", "represented and described here", "and described here follow", "described here follow uniprot", "here follow uniprot standard", "follow uniprot standard practice", "uniprot standard practice whereby", "standard practice whereby coordinates", "practice whereby coordinates refer", "whereby coordinates refer to", "coordinates refer to the", "refer to the translated", "to the translated protein", "the translated protein before", "translated protein before any", "protein before any further", "before any further processing.", "any further processing. histone", "further processing. histone literature", "processing. histone literature typically", "histone literature typically refers", "literature typically refers to", "typically refers to coordinates", "refers to coordinates of", "to coordinates of the", "coordinates of the protein", "of the protein after", "the protein after the", "protein after the initiating", "after the initiating methionine", "the initiating methionine has", "initiating methionine has been", "methionine has been removed.", "has been removed. therefore", "been removed. therefore the", "removed. therefore the coordinates", "therefore the coordinates of", "coordinates of post translated", "of post translated residues", "post translated residues in", "translated residues in the", "residues in the reactome", "in the reactome database", "the reactome database and", "reactome database and described", "database and described here", "and described here are", "described here are frequently", "here are frequently +1", "are frequently +1 when", "frequently +1 when compared", "+1 when compared with", "when compared with the", "compared with the literature.", "arginine methylation is a common", "methylation is a common post", "is a common post translational", "a common post translational modification", "post translational modification around", "translational modification around 2%", "modification around 2% of", "around 2% of arginine residues", "2% of arginine residues are", "of arginine residues are methylated", "arginine residues are methylated in", "residues are methylated in rat", "are methylated in rat liver", "methylated in rat liver nuclei", "rat liver nuclei boffa", "liver nuclei boffa et", "nuclei boffa et al.", "boffa et al. 1977 .", "et al. 1977 . arginine", "al. 1977 . arginine can", "1977 . arginine can be", ". arginine can be methylated", "arginine can be methylated in", "can be methylated in 3", "be methylated in 3 different", "methylated in 3 different ways:", "in 3 different ways: monomethylarginine", "different ways: monomethylarginine mma", "mma ng ng", "ng asymmetric dimethylarginine adma", "dimethylarginine adma and", "adma and ng n'g", "and ng n'g symmetric dimethylarginine", "n'g symmetric dimethylarginine sdma", "symmetric dimethylarginine sdma .", "dimethylarginine sdma . the", "sdma . the formation of", ". the formation of mma", "formation of mma adma", "of mma adma and", "mma adma and sdma", "adma and sdma in mammalian", "and sdma in mammalian cells", "sdma in mammalian cells is", "in mammalian cells is carried", "mammalian cells is carried out", "cells is carried out by", "is carried out by members", "carried out by members of", "out by members of a", "by members of a family", "members of a family of", "of a family of nine", "a family of nine protein", "family of nine protein arginine", "of nine protein arginine methyltransferases", "protein arginine methyltransferases prmts", "prmts bedford &", "bedford & clarke 2009 .", "& clarke 2009 .

type", "clarke 2009 .

type i", ".

type i ii", "

type i ii and", "i ii and iii", "ii and iii prmts generate", "and iii prmts generate mma", "iii prmts generate mma on", "prmts generate mma on one", "generate mma on one of", "mma on one of the", "on one of the two", "one of the two terminal", "the two terminal guanidino", "two terminal guanidino nitrogen", "terminal guanidino nitrogen atoms.", "guanidino nitrogen atoms. subsequent generation", "nitrogen atoms. subsequent generation of", "atoms. subsequent generation of asymmetric", "subsequent generation of asymmetric dimethylarginine", "of asymmetric dimethylarginine adma", "dimethylarginine adma is", "adma is catalysed by", "is catalysed by the type", "catalysed by the type i", "by the type i enzymes", "the type i enzymes prmt1", "i enzymes prmt1 prmt2", "prmt1 prmt2 prmt3", "prmt2 prmt3 co", "prmt3 co activator associated", "co activator associated arginine methyltransferase", "activator associated arginine methyltransferase 1", "arginine methyltransferase 1 carm1", "carm1 prmt6 and", "prmt6 and prmt8. production of", "and prmt8. production of symmetric", "prmt8. production of symmetric dimethylarginine", "of symmetric dimethylarginine sdma", "dimethylarginine sdma is", "sdma is catalysed by", "catalysed by the type ii", "by the type ii enzymes", "the type ii enzymes prmt5", "type ii enzymes prmt5 and", "ii enzymes prmt5 and prmt7.", "enzymes prmt5 and prmt7. on", "prmt5 and prmt7. on certain", "and prmt7. on certain substrates", "on certain substrates prmt7", "certain substrates prmt7 also", "substrates prmt7 also functions", "prmt7 also functions as a", "also functions as a type", "functions as a type iii", "as a type iii enzyme", "type iii enzyme generating", "iii enzyme generating mma", "enzyme generating mma only.", "generating mma only. prmt9 activity", "mma only. prmt9 activity has", "only. prmt9 activity has not", "prmt9 activity has not been", "activity has not been characterized.", "has not been characterized. no", "not been characterized. no known", "been characterized. no known enzyme", "characterized. no known enzyme is", "no known enzyme is capable", "known enzyme is capable of", "enzyme is capable of both", "is capable of both adma", "capable of both adma and", "of both adma and sdma", "both adma and sdma modifications.", "adma and sdma modifications. arginine", "and sdma modifications. arginine methylation", "sdma modifications. arginine methylation is", "modifications. arginine methylation is regarded", "arginine methylation is regarded as", "methylation is regarded as highly", "is regarded as highly stable", "as highly stable no", "highly stable no arginine", "stable no arginine demethylases", "no arginine demethylases are known", "demethylases are known yang", "are known yang &", "known yang & bedford", "yang & bedford 2013 .", "& bedford 2013 .

most", "bedford 2013 .

most prmts", "2013 .

most prmts methylate", ".

most prmts methylate glycine", "prmts methylate glycine and", "methylate glycine and arginine", "glycine and arginine rich", "and arginine rich gar", "rich gar motifs", "gar motifs in their", "in their substrates boffa", "their substrates boffa et", "substrates boffa et al.", "et al. 1977 . carm1", "al. 1977 . carm1 methylates", "1977 . carm1 methylates a", ". carm1 methylates a proline", "a proline glycine", "glycine and methionine rich", "and methionine rich pgm", "rich pgm motif", "pgm motif cheng", "motif cheng et al.", "cheng et al. 2007 .", "et al. 2007 . prmt5", "al. 2007 . prmt5 can", "2007 . prmt5 can dimethylate", ". prmt5 can dimethylate arginine", "prmt5 can dimethylate arginine residues", "can dimethylate arginine residues in", "dimethylate arginine residues in gar", "arginine residues in gar and", "residues in gar and pgm", "in gar and pgm motifs", "and pgm motifs cheng", "pgm motifs cheng et", "motifs cheng et al.", "et al. 2007 branscombe", "al. 2007 branscombe et", "2007 branscombe et al.", "branscombe et al. 2001 .", "et al. 2001 .

prmts", "al. 2001 .

prmts are", "2001 .

prmts are widely", ".

prmts are widely expressed", "

prmts are widely expressed and", "are widely expressed and are", "widely expressed and are constitutively", "expressed and are constitutively active", "and are constitutively active as", "are constitutively active as purified", "constitutively active as purified recombinant", "active as purified recombinant proteins.", "as purified recombinant proteins. however", "recombinant proteins. however prmt", "proteins. however prmt activity", "however prmt activity can", "prmt activity can be regulated", "activity can be regulated through", "can be regulated through ptms", "regulated through ptms association", "through ptms association with", "ptms association with regulatory", "with regulatory proteins subcellular", "regulatory proteins subcellular compartmentalization", "proteins subcellular compartmentalization and", "subcellular compartmentalization and factors that", "compartmentalization and factors that affect", "and factors that affect enzyme", "factors that affect enzyme substrate", "that affect enzyme substrate interactions.", "affect enzyme substrate interactions. the", "enzyme substrate interactions. the target", "substrate interactions. the target sites", "interactions. the target sites of", "the target sites of prmts", "target sites of prmts are", "sites of prmts are influenced", "of prmts are influenced by", "prmts are influenced by the", "are influenced by the presence", "influenced by the presence of", "by the presence of other", "the presence of other ptms", "presence of other ptms on", "of other ptms on their", "other ptms on their substrates.", "ptms on their substrates. the", "on their substrates. the best", "their substrates. the best characterized", "substrates. the best characterized examples", "the best characterized examples of", "best characterized examples of this", "characterized examples of this are", "examples of this are for", "of this are for histones.", "this are for histones. histone", "are for histones. histone h3", "for histones. histone h3 lysine", "histones. histone h3 lysine 19", "histone h3 lysine 19 acetylation", "lysine 19 acetylation h3k18ac", "acetylation h3k18ac primes", "h3k18ac primes the histone", "primes the histone tail for", "the histone tail for asymmetric", "histone tail for asymmetric dimethylation", "tail for asymmetric dimethylation at", "for asymmetric dimethylation at arginine", "asymmetric dimethylation at arginine 18", "at arginine 18 h3r17me2a", "18 h3r17me2a by", "by carm1 an et", "carm1 an et al.", "et al. 2003 daujat", "al. 2003 daujat et", "2003 daujat et al.", "et al. 2002 yue", "al. 2002 yue et", "2002 yue et al.", "yue et al. 2007 .", "et al. 2007 . h3", "al. 2007 . h3 lysine", "2007 . h3 lysine 10", ". h3 lysine 10 acetylation", "lysine 10 acetylation h3k9ac", "acetylation h3k9ac blocks", "h3k9ac blocks arginine 9", "blocks arginine 9 symmetric dimethylation", "9 symmetric dimethylation h3r8me2s", "dimethylation h3r8me2s by", "by prmt5 pal et", "prmt5 pal et al.", "pal et al. 2004 .", "et al. 2004 . h4r3me2a", "al. 2004 . h4r3me2a catalyzed", "2004 . h4r3me2a catalyzed by", ". h4r3me2a catalyzed by prmt1", "h4r3me2a catalyzed by prmt1 favours", "catalyzed by prmt1 favours subsequent", "by prmt1 favours subsequent acetylation", "prmt1 favours subsequent acetylation of", "favours subsequent acetylation of the", "subsequent acetylation of the histone", "acetylation of the histone h4", "of the histone h4 tail", "histone h4 tail huang", "h4 tail huang et", "tail huang et al.", "huang et al. 2005 .", "et al. 2005 . at", "al. 2005 . at the", "2005 . at the same", ". at the same time", "at the same time histone", "the same time histone h4", "same time histone h4 lysine", "time histone h4 lysine 5", "histone h4 lysine 5 acetylation", "lysine 5 acetylation h4k5ac", "acetylation h4k5ac makes", "h4k5ac makes the h4r3", "makes the h4r3 motif a", "the h4r3 motif a better", "h4r3 motif a better substrate", "motif a better substrate for", "a better substrate for prmt5", "better substrate for prmt5 compared", "substrate for prmt5 compared with", "for prmt5 compared with prmt1", "compared with prmt1 thereby", "with prmt1 thereby moving", "prmt1 thereby moving the", "thereby moving the balance from", "moving the balance from an", "the balance from an activating", "balance from an activating adma", "from an activating adma mark", "an activating adma mark to", "activating adma mark to a", "adma mark to a suppressive", "mark to a suppressive sdma", "to a suppressive sdma mark", "a suppressive sdma mark at", "suppressive sdma mark at the", "sdma mark at the h4r3", "mark at the h4r3 motif", "the h4r3 motif feng", "h4r3 motif feng et", "motif feng et al.", "feng et al. 2011 .", "et al. 2011 . finally", "al. 2011 . finally methylation", "2011 . finally methylation of", ". finally methylation of histone", "finally methylation of histone h3", "methylation of histone h3 on", "of histone h3 on arginine", "histone h3 on arginine 3", "on arginine 3 h3r2me2a", "3 h3r2me2a by", "h3r2me2a by prmt6 blocks", "by prmt6 blocks methylation of", "prmt6 blocks methylation of h3", "blocks methylation of h3 lysine", "methylation of h3 lysine 5", "of h3 lysine 5 by", "h3 lysine 5 by the", "lysine 5 by the mll", "5 by the mll complex", "the mll complex h3k4me3", "h3k4me3 and vice", "and vice versa methylation", "vice versa methylation of", "versa methylation of h3k4me3", "methylation of h3k4me3 prevents h3r2me2a", "of h3k4me3 prevents h3r2me2a methylation", "prevents h3r2me2a methylation guccione", "h3r2me2a methylation guccione et", "methylation guccione et al.", "et al. 2007 kirmizis", "al. 2007 kirmizis et", "2007 kirmizis et al.", "et al. 2007 hyllus", "al. 2007 hyllus et", "2007 hyllus et al.", "hyllus et al. 2007 .", "et al. 2007 . n.b.", "al. 2007 . n.b. the", "2007 . n.b. the coordinates", ". n.b. the coordinates of", "n.b. the coordinates of post", "the coordinates of post translational", "coordinates of post translational modifications", "of post translational modifications represented", "post translational modifications represented and", "translational modifications represented and described", "modifications represented and described here", "represented and described here follow", "and described here follow uniprot", "described here follow uniprot standard", "here follow uniprot standard practice", "follow uniprot standard practice whereby", "uniprot standard practice whereby coordinates", "standard practice whereby coordinates refer", "practice whereby coordinates refer to", "whereby coordinates refer to the", "coordinates refer to the translated", "refer to the translated protein", "to the translated protein before", "the translated protein before any", "translated protein before any further", "protein before any further processing.", "before any further processing. histone", "any further processing. histone literature", "further processing. histone literature typically", "processing. histone literature typically refers", "histone literature typically refers to", "literature typically refers to coordinates", "typically refers to coordinates of", "refers to coordinates of the", "to coordinates of the protein", "coordinates of the protein after", "of the protein after the", "the protein after the initiating", "protein after the initiating methionine", "after the initiating methionine has", "the initiating methionine has been", "initiating methionine has been removed.", "methionine has been removed. therefore", "has been removed. therefore the", "been removed. therefore the coordinates", "removed. therefore the coordinates of", "therefore the coordinates of post", "the coordinates of post translated", "coordinates of post translated residues", "of post translated residues in", "post translated residues in the", "translated residues in the reactome", "residues in the reactome database", "in the reactome database and", "the reactome database and described", "reactome database and described here", "database and described here are", "and described here are frequently", "described here are frequently +1", "here are frequently +1 when", "are frequently +1 when compared", "frequently +1 when compared with", "+1 when compared with the", "when compared with the literature." ] }, { "record_id": "GLY_000594_1_268", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3232142", "r hsa", "hsa 3232142", "r hsa 3232142" ] }, { "record_id": "GLY_000594_1_268", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sumoylation of", "of ubiquitinylation", "ubiquitinylation proteins", "sumoylation of ubiquitinylation", "of ubiquitinylation proteins", "sumoylation of ubiquitinylation proteins", "several ubiquitin", "ubiquitin e3", "e3 ligases", "ligases are", "are regulated", "regulated by", "by sumoylation", "reviewed in", "in wilson", "wilson and", "and heaton", "heaton 2008", "2008 .", ". sumoylation", "sumoylation 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of", "import of mdm2", "mdm2 the", "the e3 ligase", "e3 ligase that", "ligase that ubiquitinylates", "that ubiquitinylates tp53", "tp53 p53", "p53 . sumoylation", ". sumoylation of", "sumoylation of vhl", "of vhl abolishes", "vhl abolishes its", "abolishes its ubiquitin", "its ubiquitin ligase", "ubiquitin ligase activity.", "ligase activity. herc2", "herc2 rnf168", "rnf168 and", "and brca1 are", "brca1 are ubiquitin", "are ubiquitin ligases", "ubiquitin ligases that", "ligases that are", "that are sumoylated", "are sumoylated during", "sumoylated during dna", "during dna damage", "dna damage response", "damage response and", "response and repair.", "several ubiquitin e3 ligases", "ubiquitin e3 ligases are", "e3 ligases are regulated", "ligases are regulated by", "are regulated by sumoylation", "by sumoylation reviewed", "sumoylation reviewed in", "reviewed in wilson and", "in wilson and heaton", "wilson and heaton 2008", "and heaton 2008 .", "heaton 2008 . sumoylation", "2008 . sumoylation appears", ". sumoylation appears to", "sumoylation appears to be", "appears to be necessary", "to be necessary for", "be necessary for nuclear", "necessary for nuclear import", "for nuclear import of", "nuclear import of mdm2", "of mdm2 the", "mdm2 the e3", "the e3 ligase that", "e3 ligase that ubiquitinylates", "ligase that ubiquitinylates tp53", "ubiquitinylates tp53 p53", "tp53 p53 .", "p53 . sumoylation of", ". sumoylation of vhl", "sumoylation of vhl abolishes", "of vhl abolishes its", "vhl abolishes its ubiquitin", "abolishes its ubiquitin ligase", "its ubiquitin ligase activity.", "ubiquitin ligase activity. herc2", "activity. herc2 rnf168", "rnf168 and brca1", "and brca1 are ubiquitin", "brca1 are ubiquitin ligases", "are ubiquitin ligases that", "ubiquitin ligases that are", "ligases that are sumoylated", "that are sumoylated during", "are sumoylated during dna", "sumoylated during dna damage", "during dna damage response", "dna damage response and", "damage 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vhl abolishes its", "of vhl abolishes its ubiquitin", "vhl abolishes its ubiquitin ligase", "abolishes its ubiquitin ligase activity.", "its ubiquitin ligase activity. herc2", "ligase activity. herc2 rnf168", "herc2 rnf168 and", "rnf168 and brca1 are", "and brca1 are ubiquitin ligases", "brca1 are ubiquitin ligases that", "are ubiquitin ligases that are", "ubiquitin ligases that are sumoylated", "ligases that are sumoylated during", "that are sumoylated during dna", "are sumoylated during dna damage", "sumoylated during dna damage response", "during dna damage response and", "dna damage response and repair." ] }, { "record_id": "GLY_000594_1_269", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3238698", "r hsa", "hsa 3238698", "r hsa 3238698" ] }, { "record_id": "GLY_000594_1_269", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "wnt ligand", "ligand biogenesis", "biogenesis and", "and trafficking", "wnt ligand biogenesis", "ligand biogenesis and", "biogenesis and trafficking", "wnt ligand biogenesis and", "ligand biogenesis and trafficking", "wnt ligand biogenesis and trafficking", "19 wnt", "wnt proteins", "proteins have", "have been", "been identified", "identified in", "in human", "human cells.", "the wnts", "wnts are", "are members", "members of", "of a", "a conserved", "conserved metazoan", "metazoan family", "family of", "of secreted", "secreted morphogens", "morphogens that", "that activate", "activate several", "several signaling", "signaling pathways", "pathways in", "in the", "the responding", "responding cell:", "cell: the", "the canonical", "beta catenin", "wnt signaling", "signaling cascade", "cascade and", "and several", "several non", "non canonical", "canonical pathways", "including the", "the planar", "planar cell", "cell polarity", "the regulation", "regulation of", "of intracellular", "intracellular calcium", "calcium signaling", "signaling and", "activation of", "of jnk", "jnk kinases.", "proteins exist", "exist in", "in a", "a gradient", "gradient outside", "outside the", "the secreting", "secreting cell", "cell and", "and are", "are able", "able to", "to act", "act over", "over both", "both short", "short and", "and long", "long ranges", "ranges to", "to promote", "promote proliferation", "changes in", "in cell", "cell migration", "migration and", "and polarity", "polarity and", "and tissue", "tissue homeostasis", "among others", "reviewed in", "in saito", "saito diaz", "diaz et", "et al", "willert and", "and nusse", "2012 .", "


the wnts", "are ~40kda", "~40kda proteins", "proteins with", "with 23", "23 conserved", "conserved cysteine", "cysteine residues", "residues in", "the n", "n terminal", "terminal that", "that may", "may form", "form intramolecular", "intramolecular disulphide", "disulphide bonds.", "bonds. they", "they also", "also contain", "contain an", "an n", "terminal signal", "signal sequence", "sequence and", "and a", "a number", "number of", "of n", "n linked", "linked glycosylation", "glycosylation sites", "janda et", ". in", "in addition", "addition to", "to being", "being glycosylated", "are also", "also lipid", "lipid modified", "modified in", "the endoplasmic", "endoplasmic reticulum", "reticulum by", "by a", "a wnt", "wnt specific", "specific o", "o acyl", "acyl transferase", "contributing to", "to their", "their characteristic", "characteristic hydrophobicity.", "porcn dependent", "dependent palmitoylation", "palmitoylation is", "is required", "required for", "for the", "the secretion", "secretion of", "of wnt", "wnt as", "as well", "well as", "as its", "its signaling", "signaling activity", "as either", "either depletion", "depletion of", "of porcn", "porcn or", "or mutation", "mutation of", "of the", "the conserved", "conserved serine", "serine acylation", "acylation site", "site results", "results in", "the intracellular", "intracellular accumulation", "accumulation of", "takada et", "barrott et", "biechele et", "in willert", "2012 .


secretion", ".


secretion of", "wnt requires", "requires a", "of other", "other dedicated", "dedicated factors", "factors including", "the sorting", "sorting receptor", "receptor wntless", "also knownas", "knownas evi", "and gpr177", "which binds", "binds wnt", "wnt and", "and escorts", "escorts it", "it to", "to the", "the cell", "cell surface", "banziger et", "bartscherer et", "goodman et", "2006 .", "specific retromer", "retromer containing", "containing snx3", "snx3 is", "is subsequently", "subsequently required", "the recycling", "recycling of", "of wls", "wls back", "back to", "the golgi", "in herr", "herr et", "johannes and", "and wunder", "2011 .", "once at", "at the", "wnt makes", "makes extensive", "extensive contacts", "contacts with", "with components", "components of", "the extracellular", "extracellular matrix", "matrix such", "such as", "as heparan", "heparan sulphate", "sulphate proteoglycans", "and may", "may be", "be bound", "bound by", "by any", "any of", "of regulatory", "regulatory proteins", "including wifs", "wifs and", "and sfrps.", "sfrps. the", "the diffusion", "diffusion of", "the wnt", "ligand may", "be aided", "aided by", "by its", "its packing", "packing either", "either into", "into wnt", "wnt multimers", "exosomes or", "or onto", "onto lipoprotein", "lipoprotein particles", "particles to", "to shield", "shield the", "the hydrophobic", "hydrophobic lipid", "lipid adducts", "adducts from", "from the", "the aqueous", "aqueous extracellular", "extracellular environment", "gross et", "luga et", "korkut et", "2012 .

", "19 wnt proteins", "wnt proteins have", "proteins have been", "have been identified", "been identified in", "identified in human", "in human cells.", "cells. the", "the wnts are", "wnts are members", "are members of", "members of a", "of a conserved", "a conserved metazoan", "conserved metazoan family", "metazoan family of", "family of secreted", "of secreted morphogens", "secreted morphogens that", "morphogens that activate", "that activate several", "activate several signaling", "several signaling pathways", "signaling pathways in", "pathways in the", "in the responding", "the responding cell:", "responding cell: the", "cell: the canonical", "canonical beta", "catenin wnt", "wnt signaling cascade", "signaling cascade and", "cascade and several", "and several non", "several non canonical", "non canonical pathways", "pathways including", "including the planar", "the planar cell", "planar cell polarity", "polarity pcp", "the regulation of", "regulation of intracellular", "of intracellular calcium", "intracellular calcium signaling", "calcium signaling and", "and activation", "activation of jnk", "of jnk kinases.", "kinases. wnt", "wnt proteins exist", "proteins exist in", "exist in a", "in a gradient", "a gradient outside", "gradient outside the", "outside the secreting", "the secreting cell", "secreting cell and", "cell and are", "and are able", "are able to", "able to act", "to act over", "act over both", "over both short", "both short and", "short and long", "and long ranges", "long ranges to", "ranges to promote", "to promote proliferation", "proliferation changes", "changes in cell", "in cell migration", "cell migration and", "migration and polarity", "and polarity and", "polarity and tissue", "and tissue homeostasis", "homeostasis among", "others reviewed", "reviewed in saito", "in saito diaz", "saito diaz et", "diaz et al", "al 2012", "2012 willert", "willert and nusse", "nusse 2012", ".


the", "


the wnts are", "wnts are ~40kda", "are ~40kda proteins", "~40kda proteins with", "proteins with 23", "with 23 conserved", "23 conserved cysteine", "conserved cysteine residues", "cysteine residues in", "residues in the", "in the n", "the n terminal", "n terminal that", "terminal that may", "that may form", "may form intramolecular", "form intramolecular disulphide", "intramolecular disulphide bonds.", "disulphide bonds. they", "bonds. they also", "they also contain", "also contain an", "contain an n", "an n terminal", "n terminal signal", "terminal signal sequence", "signal sequence and", "sequence and a", "and a number", "a number of", "number of n", "of n linked", "n linked glycosylation", "linked glycosylation sites", "sites janda", "janda et al", "2012 . in", ". in addition", "in addition to", "addition to being", "to being glycosylated", "glycosylated wnts", "wnts are also", "are also lipid", "also lipid modified", "lipid modified in", "modified in the", "in the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum by", "reticulum by a", "by a wnt", "a wnt specific", "wnt specific o", "specific o acyl", "o acyl transferase", "transferase porcupine", "porcupine porcn", "contributing to their", "to their characteristic", "their characteristic hydrophobicity.", "hydrophobicity. porcn", "porcn dependent palmitoylation", "dependent palmitoylation is", "palmitoylation is required", "is required for", "required for the", "for the secretion", "the secretion of", "secretion of wnt", "of wnt as", "wnt as well", "as well as", "well as its", "as its signaling", "its signaling activity", "activity as", "as either depletion", "either depletion of", "depletion of porcn", "of porcn or", "porcn or mutation", "or mutation of", "mutation of the", "of the conserved", "the conserved serine", "conserved serine acylation", "serine acylation site", "acylation site results", "site results in", "results in the", "in the intracellular", "the intracellular accumulation", "intracellular accumulation of", "accumulation of wnt", "of wnt ligand", "ligand takada", "takada et al", "al 2006", "2006 barrott", "barrott et al", "al 2011", "2011 biechele", "biechele et al", "2011 reviewed", "reviewed in willert", "in willert and", "2012 .


secretion of", ".


secretion of wnt", "of wnt requires", "wnt requires a", "requires a number", "number of other", "of other dedicated", "other dedicated factors", "dedicated factors including", "factors including the", "including the sorting", "the sorting receptor", "sorting receptor wntless", "wntless wls", "also knownas evi", "evi sprinter", "sprinter and", "which binds wnt", "binds wnt and", "wnt and escorts", "and escorts it", "escorts it to", "it to the", "to the cell", "the cell surface", "surface banziger", "banziger et al", "2006 bartscherer", "bartscherer et al", "2006 goodman", "goodman et al", ". a", "wnt specific retromer", "specific retromer containing", "retromer containing snx3", "containing snx3 is", "snx3 is subsequently", "is subsequently required", "subsequently required for", "for the recycling", "the recycling of", "recycling of wls", "of wls back", "wls back to", "back to the", "to the golgi", "golgi reviewed", "reviewed in herr", "in herr et", "herr et al", "2012 johannes", "johannes and wunder", "once at the", "at the cell", "surface wnt", "wnt makes extensive", "makes extensive contacts", "extensive contacts with", "contacts with components", "with components of", "components of the", "of the extracellular", "the extracellular matrix", "extracellular matrix such", "matrix such as", "such as heparan", "as heparan sulphate", "heparan sulphate proteoglycans", "proteoglycans hspgs", "hspgs and", "and may be", "may be bound", "be bound by", "bound by any", "by any of", "any of a", "of a number", "number of regulatory", "of regulatory proteins", "proteins including", "including wifs and", "wifs and sfrps.", "and sfrps. the", "sfrps. the diffusion", "the diffusion of", "diffusion of the", "of the wnt", "the wnt ligand", "wnt ligand may", "ligand may be", "may be aided", "be aided by", "aided by its", "by its packing", "its packing either", "packing either into", "either into wnt", "into wnt multimers", "multimers exosomes", "exosomes or onto", "or onto lipoprotein", "onto lipoprotein particles", "lipoprotein particles to", "particles to shield", "to shield the", "shield the hydrophobic", "the hydrophobic lipid", "hydrophobic lipid adducts", "lipid adducts from", "adducts from the", "from the aqueous", "the aqueous extracellular", "aqueous extracellular environment", "environment gross", "gross et al", "2012 luga", "luga et al", "2012 korkut", "korkut et al", "al 2009", "2009 reviewed", "2012 .

", "19 wnt proteins have", "wnt proteins have been", "proteins have been identified", "have been identified in", "been identified in human", "identified in human cells.", "human cells. the", "cells. the wnts", "the wnts are members", "wnts are members of", "are members of a", "members of a conserved", "of a conserved metazoan", "a conserved metazoan family", "conserved metazoan family of", "metazoan family of secreted", "family of secreted morphogens", "of secreted morphogens that", "secreted morphogens that activate", "morphogens that activate several", "that activate several signaling", "activate several signaling pathways", "several signaling pathways in", "signaling pathways in the", "pathways in the responding", "in the responding cell:", "the responding cell: the", "responding cell: the canonical", "the canonical beta", "canonical beta catenin", "beta catenin wnt", "catenin wnt signaling", "wnt signaling cascade and", "signaling cascade and several", "cascade and several non", "and several non canonical", "several non canonical pathways", "canonical pathways including", "pathways including the", "including the planar cell", "the planar cell polarity", "cell polarity pcp", "pcp the", "the regulation of intracellular", "regulation of intracellular calcium", "of intracellular calcium signaling", "intracellular calcium signaling and", "signaling and activation", "and activation of", "activation of jnk kinases.", "jnk kinases. wnt", "kinases. wnt proteins", "wnt proteins exist in", "proteins exist in a", "exist in a gradient", "in a gradient outside", "a gradient outside the", "gradient outside the secreting", "outside the secreting cell", "the secreting cell and", "secreting cell and are", "cell and are able", "and are able to", "are able to act", "able to act over", "to act over both", "act over both short", "over both short and", "both short and long", "short and long ranges", "and long ranges to", "long ranges to promote", "ranges to promote proliferation", "promote proliferation changes", "proliferation changes in", "changes in cell migration", "in cell migration and", "cell migration and polarity", "migration and polarity and", "and polarity and tissue", "polarity and tissue homeostasis", "tissue homeostasis among", "homeostasis among others", "among others reviewed", "others reviewed in", "reviewed in saito diaz", "in saito diaz et", "saito diaz et al", "et al 2012", "2012 willert and", "and nusse 2012", "nusse 2012 .", "2012 .


the", ".


the wnts", "


the wnts are ~40kda", "wnts are ~40kda proteins", "are ~40kda proteins with", "~40kda proteins with 23", "proteins with 23 conserved", "with 23 conserved cysteine", "23 conserved cysteine residues", "conserved cysteine residues in", "cysteine residues in the", "residues in the n", "in the n terminal", "the n terminal that", "n terminal that may", "terminal that may form", "that may form intramolecular", "may form intramolecular disulphide", "form intramolecular disulphide bonds.", "intramolecular disulphide bonds. they", "disulphide bonds. they also", "bonds. they also contain", "they also contain an", "also contain an n", "contain an n terminal", "an n terminal signal", "n terminal signal sequence", "terminal signal sequence and", "signal sequence and a", "sequence and a number", "and a number of", "a number of n", "number of n linked", "of n linked glycosylation", "n linked glycosylation sites", "glycosylation sites janda", "sites janda et", "al 2012 .", "2012 . in addition", ". in addition to", "in addition to being", "addition to being glycosylated", "being glycosylated wnts", "glycosylated wnts are", "wnts are also lipid", "are also lipid modified", "also lipid modified in", "lipid modified in the", "modified in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum by", "endoplasmic reticulum by a", "reticulum by a wnt", "by a wnt specific", "a wnt specific o", "wnt specific o acyl", "specific o acyl transferase", "acyl transferase porcupine", "porcn contributing", "contributing to their characteristic", "to their characteristic hydrophobicity.", "characteristic hydrophobicity. porcn", "hydrophobicity. porcn dependent", "porcn dependent palmitoylation is", "dependent palmitoylation is required", "palmitoylation is required for", "is required for the", "required for the secretion", "for the secretion of", "the secretion of wnt", "secretion of wnt as", "of wnt as well", "wnt as well as", "as well as its", "well as its signaling", "as its signaling activity", "signaling activity as", "activity as either", "as either depletion of", "either depletion of porcn", "depletion of porcn or", "of porcn or mutation", "porcn or mutation of", "or mutation of the", "mutation of the conserved", "of the conserved serine", "the conserved serine acylation", "conserved serine acylation site", "serine acylation site results", "acylation site results in", "site results in the", "results in the intracellular", "in the intracellular accumulation", "the intracellular accumulation of", "intracellular accumulation of wnt", "accumulation of wnt ligand", "wnt ligand takada", "ligand takada et", "et al 2006", "2006 barrott et", "et al 2011", "2011 biechele et", "2011 reviewed in", "reviewed in willert and", "in willert and nusse", "nusse 2012 .


secretion", "2012 .


secretion of wnt", ".


secretion of wnt requires", "of wnt requires a", "wnt requires a number", "requires a number of", "a number of other", "number of other dedicated", "of other dedicated factors", "other dedicated factors including", "dedicated factors including the", "factors including the sorting", "including the sorting receptor", "the sorting receptor wntless", "receptor wntless wls", "wls also", "knownas evi sprinter", "sprinter and gpr177", "gpr177 which", "which binds wnt and", "binds wnt and escorts", "wnt and escorts it", "and escorts it to", "escorts it to the", "it to the cell", "to the cell surface", "cell surface banziger", "surface banziger et", "2006 bartscherer et", "2006 goodman et", "al 2006 .", "2006 . a", ". a wnt", "a wnt specific retromer", "wnt specific retromer containing", "specific retromer containing snx3", "retromer containing snx3 is", "containing snx3 is subsequently", "snx3 is subsequently required", "is subsequently required for", "subsequently required for the", "required for the recycling", "for the recycling of", "the recycling of wls", "recycling of wls back", "of wls back to", "wls back to the", "back to the golgi", "the golgi reviewed", "golgi reviewed in", "reviewed in herr et", "in herr et al", "2012 johannes and", "wunder 2011", ". once", "once at the cell", "at the cell surface", "cell surface wnt", "surface wnt makes", "wnt makes extensive contacts", "makes extensive contacts with", "extensive contacts with components", "contacts with components of", "with components of the", "components of the extracellular", "of the extracellular matrix", "the extracellular matrix such", "extracellular matrix such as", "matrix such as heparan", "such as heparan sulphate", "as heparan sulphate proteoglycans", "sulphate proteoglycans hspgs", "hspgs and may", "and may be bound", "may be bound by", "be bound by any", "bound by any of", "by any of a", "any of a number", "of a number of", "a number of regulatory", "number of regulatory proteins", "regulatory proteins including", "proteins including wifs", "including wifs and sfrps.", "wifs and sfrps. the", "and sfrps. the diffusion", "sfrps. the diffusion of", "the diffusion of the", "diffusion of the wnt", "of the wnt ligand", "the wnt ligand may", "wnt ligand may be", "ligand may be aided", "may be aided by", "be aided by its", "aided by its packing", "by its packing either", "its packing either into", "packing either into wnt", "either into wnt multimers", "wnt multimers exosomes", "multimers exosomes or", "exosomes or onto lipoprotein", "or onto lipoprotein particles", "onto lipoprotein particles to", "lipoprotein particles to shield", "particles to shield the", "to shield the hydrophobic", "shield the hydrophobic lipid", "the hydrophobic lipid adducts", "hydrophobic lipid adducts from", "lipid adducts from the", "adducts from the aqueous", "from the aqueous extracellular", "the aqueous extracellular environment", "extracellular environment gross", "environment gross et", "2012 luga et", "2012 korkut et", "et al 2009", "2009 reviewed in", "nusse 2012 .


the wnts", ".


the wnts are", "


the wnts are ~40kda proteins", "wnts are ~40kda proteins with", "are ~40kda proteins with 23", "~40kda proteins with 23 conserved", "proteins with 23 conserved cysteine", "with 23 conserved cysteine residues", "23 conserved cysteine residues in", "conserved cysteine residues in the", "cysteine residues in the n", "residues in the n terminal", "in the n terminal that", "the n terminal that may", "n terminal that may form", "terminal that may form intramolecular", "that may form intramolecular disulphide", "may form intramolecular disulphide bonds.", "form intramolecular disulphide bonds. they", "intramolecular disulphide bonds. they also", "disulphide bonds. they also contain", "bonds. they also contain an", "they also contain an n", "also contain an n terminal", "contain an n terminal signal", "an n terminal signal sequence", "n terminal signal sequence and", "terminal signal sequence and a", "signal sequence and a number", "sequence and a number of", "and a number of n", "a number of n linked", "number of n linked glycosylation", "of n linked glycosylation sites", "linked glycosylation sites janda", "glycosylation sites janda et", "sites janda et al", "janda et al 2012", "et al 2012 .", "al 2012 . in", "2012 . in addition to", ". in addition to being", "in addition to being glycosylated", "to being glycosylated wnts", "being glycosylated wnts are", "glycosylated wnts are also", "wnts are also lipid modified", "are also lipid modified in", "also lipid modified in the", "lipid modified in the endoplasmic", "modified in the endoplasmic reticulum", "in the endoplasmic reticulum by", "the endoplasmic reticulum by a", "endoplasmic reticulum by a wnt", "reticulum by a wnt specific", "by a wnt specific o", "a wnt specific o acyl", "wnt specific o acyl transferase", "o acyl transferase porcupine", "transferase porcupine porcn", "porcn contributing to", "contributing to their characteristic hydrophobicity.", "their characteristic hydrophobicity. porcn", "characteristic hydrophobicity. porcn dependent", "hydrophobicity. porcn dependent palmitoylation", "porcn dependent palmitoylation is required", "dependent palmitoylation is required for", "palmitoylation is required for the", "is required for the secretion", "required for the secretion of", "for the secretion of wnt", "the secretion of wnt as", "secretion of wnt as well", "of wnt as well as", "wnt as well as its", "as well as its signaling", "well as its signaling activity", "its signaling activity as", "signaling activity as either", "activity as either depletion", "as either depletion of porcn", "either depletion of porcn or", "depletion of porcn or mutation", "of porcn or mutation of", "porcn or mutation of the", "or mutation of the conserved", "mutation of the conserved serine", "of the conserved serine acylation", "the conserved serine acylation site", "conserved serine acylation site results", "serine acylation site results in", "acylation site results in the", "site results in the intracellular", "results in the intracellular accumulation", "in the intracellular accumulation of", "the intracellular accumulation of wnt", "intracellular accumulation of wnt ligand", "of wnt ligand takada", "wnt ligand takada et", "ligand takada et al", "takada et al 2006", "al 2006 barrott", "2006 barrott et al", "barrott et al 2011", "al 2011 biechele", "2011 biechele et al", "biechele et al 2011", "al 2011 reviewed", "2011 reviewed in willert", "reviewed in willert and nusse", "and nusse 2012 .


secretion", "nusse 2012 .


secretion of", "2012 .


secretion of wnt requires", ".


secretion of wnt requires a", "of wnt requires a number", "wnt requires a number of", "requires a number of other", "a number of other dedicated", "number of other dedicated factors", "of other dedicated factors including", "other dedicated factors including the", "dedicated factors including the sorting", "factors including the sorting receptor", "including the sorting receptor wntless", "sorting receptor wntless wls", "wls also knownas", "also knownas evi sprinter", "evi sprinter and", "and gpr177 which", "gpr177 which binds", "which binds wnt and escorts", "binds wnt and escorts it", "wnt and escorts it to", "and escorts it to the", "escorts it to the cell", "it to the cell surface", "the cell surface banziger", "cell surface banziger et", "surface banziger et al", "banziger et al 2006", "al 2006 bartscherer", "2006 bartscherer et al", "bartscherer et al 2006", "al 2006 goodman", "2006 goodman et al", "goodman et al 2006", "et al 2006 .", "2006 . a wnt", ". a wnt specific", "a wnt specific retromer containing", "wnt specific retromer containing snx3", "specific retromer containing snx3 is", "retromer containing snx3 is subsequently", "containing snx3 is subsequently required", "snx3 is subsequently required for", "is subsequently required for the", "subsequently required for the recycling", "required for the recycling of", "for the recycling of wls", "the recycling of wls back", "recycling of wls back to", "of wls back to the", "wls back to the golgi", "to the golgi reviewed", "the golgi reviewed in", "golgi reviewed in herr", "reviewed in herr et al", "herr et al 2012", "al 2012 johannes", "2012 johannes and wunder", "and wunder 2011", "wunder 2011 .", "2011 . once", ". once at", "once at the cell surface", "the cell surface wnt", "cell surface wnt makes", "surface wnt makes extensive", "wnt makes extensive contacts with", "makes extensive contacts with components", "extensive contacts with components of", "contacts with components of the", "with components of the extracellular", "components of the extracellular matrix", "of the extracellular matrix such", "the extracellular matrix such as", "extracellular matrix such as heparan", "matrix such as heparan sulphate", "such as heparan sulphate proteoglycans", "heparan sulphate proteoglycans hspgs", "proteoglycans hspgs and", "hspgs and may be", "and may be bound by", "may be bound by any", "be bound by any of", "bound by any of a", "by any of a number", "any of a number of", "of a number of regulatory", "a number of regulatory proteins", "of regulatory proteins including", "regulatory proteins including wifs", "proteins including wifs and", "including wifs and sfrps. the", "wifs and sfrps. the diffusion", "and sfrps. the diffusion of", "sfrps. the diffusion of the", "the diffusion of the wnt", "diffusion of the wnt ligand", "of the wnt ligand may", "the wnt ligand may be", "wnt ligand may be aided", "ligand may be aided by", "may be aided by its", "be aided by its packing", "aided by its packing either", "by its packing either into", "its packing either into wnt", "packing either into wnt multimers", "into wnt multimers exosomes", "wnt multimers exosomes or", "multimers exosomes or onto", "exosomes or onto lipoprotein particles", "or onto lipoprotein particles to", "onto lipoprotein particles to shield", "lipoprotein particles to shield the", "particles to shield the hydrophobic", "to shield the hydrophobic lipid", "shield the hydrophobic lipid adducts", "the hydrophobic lipid adducts from", "hydrophobic lipid adducts from the", "lipid adducts from the aqueous", "adducts from the aqueous extracellular", "from the aqueous extracellular environment", "aqueous extracellular environment gross", "extracellular environment gross et", "environment gross et al", "gross et al 2012", "al 2012 luga", "2012 luga et al", "luga et al 2012", "al 2012 korkut", "2012 korkut et al", "korkut et al 2009", "al 2009 reviewed", "2009 reviewed in willert", "and nusse 2012 .

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humans", "water.
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"channels and", "others reviewed", "reviewed in veal", "in veal and", "veal and day", "and day 2011", "2011 ray", "2012 . hydrogen", ". hydrogen peroxide", "peroxide is decomposed", "is decomposed to", "decomposed to water", "to water by", "water by catalase", "catalase decomposed", "to water plus", "water plus oxidized", "plus oxidized thioredoxin", "oxidized thioredoxin by", "thioredoxin by peroxiredoxins", "peroxiredoxins and", "and decomposed to", "plus oxidized glutathione", "oxidized glutathione by", "glutathione by glutathione", "by glutathione peroxidases", "peroxidases presnell", "presnell et al.", "et al. 2013", "al. 2013 .", "reactive oxygen species such", "oxygen species such as", "species such as superoxide", "as superoxide o2.", "roor singlet", "singlet oxygen peroxynitrite", "hydroxyl radical oh.", "oh. are generated", "are generated by cellular", "generated by cellular processes", "by cellular processes such", "cellular processes such as", "processes such as respiration", "as respiration reviewed", "respiration reviewed in", "reviewed in murphy 2009", "murphy 2009 brand", "2009 brand 2010", "brand 2010 and", "2010 and redox", "and redox enzymes and", "redox enzymes and are", "enzymes and are required", "and are required for", "are required for signaling", "required for signaling yet", "for signaling yet they", "signaling yet they are", "yet they are damaging", "they are damaging due", "are damaging due to", "damaging due to their", "due to their high", "to their high reactivity", "high reactivity reviewed", "reactivity reviewed in", "reviewed in imlay 2008", "imlay 2008 buettner", "2008 buettner 2011", "buettner 2011 kavdia", "2011 kavdia 2011", "kavdia 2011 birben", "2011 birben et", "birben et al. 2012", "al. 2012 ray", "2012 ray et", "ray et al. 2012", "et al. 2012 .", "al. 2012 . aerobic", "2012 . aerobic cells", ". aerobic cells have", "aerobic cells have defenses", "cells have defenses that", "have defenses that detoxify", "defenses that detoxify reactive", "that detoxify reactive oxygen", "detoxify reactive oxygen species", "reactive oxygen species by", "oxygen species by converting", "species by converting them", "by converting them to", "converting them to less", "them to less reactive", "to less reactive products.", "less reactive products. superoxide", "reactive products. superoxide dismutases", "products. superoxide dismutases convert", "superoxide dismutases convert superoxide", "dismutases convert superoxide to", "convert superoxide to hydrogen", "superoxide to hydrogen peroxide", "to hydrogen peroxide and", "hydrogen peroxide and oxygen", "and oxygen reviewed", "oxygen reviewed in", "reviewed in fukai and", "in fukai and ushio", "fukai and ushio fukai", "and ushio fukai 2011", "ushio fukai 2011 .", "fukai 2011 . catalase", "2011 . catalase and", ". catalase and peroxidases", "catalase and peroxidases then", "and peroxidases then convert", "peroxidases then convert hydrogen", "then convert hydrogen peroxide", "convert hydrogen peroxide to", "hydrogen peroxide to water.
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humans contain 3", "water.
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and", "mitochondria and once", "and once in", "once in the cytosol", "the cytosol hydrogen", "cytosol hydrogen peroxide", "hydrogen peroxide serves as", "peroxide serves as a", "serves as a signaling", "as a signaling molecule", "a signaling molecule to", "signaling molecule to regulate", "molecule to regulate redox", "to regulate redox sensitive", "regulate redox sensitive proteins", "redox sensitive proteins such", "sensitive proteins such as", "proteins such as transcription", "such as transcription factors", "transcription factors kinases", "phosphatases ion channels", "ion channels and", "channels and others", "and others reviewed", "others reviewed in", "reviewed in veal and", "in veal and day", "veal and day 2011", "day 2011 ray", "2011 ray et", "al. 2012 . hydrogen", "2012 . hydrogen peroxide", ". hydrogen peroxide is", "hydrogen peroxide is decomposed", "peroxide is decomposed to", "is decomposed to water", "decomposed to water by", "to water by catalase", "by catalase decomposed", "catalase decomposed to", "decomposed to water plus", "to water plus oxidized", "water plus oxidized thioredoxin", "plus oxidized thioredoxin by", "oxidized thioredoxin by peroxiredoxins", "by peroxiredoxins and", "peroxiredoxins and decomposed", "and decomposed to water", "water plus oxidized glutathione", "plus oxidized glutathione by", "oxidized glutathione by glutathione", "glutathione by glutathione peroxidases", "glutathione peroxidases presnell", "peroxidases presnell et", "presnell et al. 2013", "et al. 2013 .", "reactive oxygen species such as", "oxygen species such as superoxide", "such as superoxide o2.", "o2. peroxides", "roor singlet oxygen", "oxygen peroxynitrite onoo", "onoo and", "and hydroxyl radical oh.", "radical oh. are", "oh. are generated by", "are generated by cellular processes", "generated by cellular processes such", "by cellular processes such as", "cellular processes such as respiration", "such as respiration reviewed", "as respiration reviewed in", "respiration reviewed in murphy", "in murphy 2009 brand", "murphy 2009 brand 2010", "brand 2010 and redox", "2010 and redox enzymes", "and redox enzymes and are", "redox enzymes and are required", "enzymes and are required for", "and are required for signaling", "are required for signaling yet", "required for signaling yet they", "for signaling yet they are", "signaling yet they are damaging", "yet they are damaging due", "they are damaging due to", "are damaging due to their", "damaging due to their high", "due to their high reactivity", "their high reactivity reviewed", "high reactivity reviewed in", "reactivity reviewed in imlay", "in imlay 2008 buettner", "imlay 2008 buettner 2011", "buettner 2011 kavdia 2011", "kavdia 2011 birben et", "2011 birben et al.", "et al. 2012 ray", "al. 2012 ray et", "2012 ray et al.", "ray et al. 2012 .", "et al. 2012 . aerobic", "al. 2012 . aerobic cells", "2012 . aerobic cells have", ". aerobic cells have defenses", "aerobic cells have defenses that", "cells have defenses that detoxify", "have defenses that detoxify reactive", "defenses that detoxify reactive oxygen", "that detoxify reactive oxygen species", "detoxify reactive oxygen species by", "reactive oxygen species by converting", "oxygen species by converting them", "species by converting them to", "by converting them to less", "converting them to less reactive", "them to less reactive products.", "to less reactive products. superoxide", "less reactive products. superoxide dismutases", "reactive products. superoxide dismutases convert", "products. superoxide dismutases convert superoxide", "superoxide dismutases convert superoxide to", "dismutases convert superoxide to hydrogen", "convert superoxide to hydrogen peroxide", "superoxide to hydrogen peroxide and", "to hydrogen peroxide and oxygen", "peroxide and oxygen reviewed", "and oxygen reviewed in", "oxygen reviewed in fukai", "reviewed in fukai and ushio", "in fukai and ushio fukai", "fukai and ushio fukai 2011", "and ushio fukai 2011 .", "ushio fukai 2011 . catalase", "fukai 2011 . catalase and", "2011 . catalase and peroxidases", ". catalase and peroxidases then", "catalase and peroxidases then convert", "and peroxidases then convert hydrogen", "peroxidases then convert hydrogen peroxide", "then convert hydrogen peroxide to", "convert hydrogen peroxide to water.
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humans contain", "peroxide to water.
humans contain 3", "to water.
humans contain 3 superoxide", "water.
humans contain 3 superoxide dismutases:", "contain 3 superoxide dismutases: sod1", "3 superoxide dismutases: sod1 is", "superoxide dismutases: sod1 is located", "dismutases: sod1 is located in", "sod1 is located in the", "is located in the cytosol", "located in the cytosol and", "in the cytosol and mitochondrial", "the cytosol and mitochondrial intermembrane", "cytosol and mitochondrial intermembrane space", "mitochondrial intermembrane space sod2", "intermembrane space sod2 is", "space sod2 is located", "sod2 is located in the", "is located in the mitochondrial", "located in the mitochondrial matrix", "the mitochondrial matrix and", "mitochondrial matrix and sod3", "matrix and sod3 is", "and sod3 is located in", "sod3 is located in the", "is located in the extracellular", "located in the extracellular region.", "in the extracellular region. superoxide", "extracellular region. superoxide a", "region. superoxide a negative", "superoxide a negative ion", "a negative ion is", "negative ion is unable", "ion is unable to", "is unable to easily cross", "unable to easily cross membranes", "to easily cross membranes and", "easily cross membranes and tends", "cross membranes and tends to", "membranes and tends to remain", "and tends to remain in", "tends to remain in the", "to remain in the compartment", "remain in the compartment where", "in the compartment where it", "the compartment where it was", "compartment where it was produced.", "where it was produced. hydrogen", "it was produced. hydrogen peroxide", "produced. hydrogen peroxide one", "hydrogen peroxide one of", "peroxide one of the", "one of the products of", "of the products of superoxide", "the products of superoxide dismutase", "of superoxide dismutase is", "superoxide dismutase is able", "dismutase is able to", "is able to diffuse across", "able to diffuse across membranes", "to diffuse across membranes and", "diffuse across membranes and pass", "across membranes and pass through", "membranes and pass through 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"probably the first nucleoporin", "the first nucleoporin that", "first nucleoporin that dissociates", "nucleoporin that dissociates from", "that dissociates from the", "dissociates from the npc", "from the npc at", "the npc at the", "npc at the start", "at the start of", "the start of mitotic", "start of mitotic npc", "of mitotic npc disassembly", "npc disassembly dultz", "disassembly dultz et", "dultz et al. 2008", "et al. 2008 .", "al. 2008 . nup98", "2008 . nup98 dissociation", ". nup98 dissociation is", "nup98 dissociation is triggered", "dissociation is triggered by", "is triggered by phosphorylation.", "triggered by phosphorylation. phosphorylation", "by phosphorylation. phosphorylation of", "phosphorylation. phosphorylation of nup98", "phosphorylation of nup98 by", "of nup98 by cdk1", "nup98 by cdk1 and", "by cdk1 and nima", "cdk1 and nima family", "and nima family kinases", "nima family kinases nek6", "family kinases nek6 and/or", "kinases nek6 and/or nek7", "nek6 and/or nek7 is", "and/or nek7 is needed", "nek7 is needed for", "is needed for nup98", "needed for nup98 dissociation", "for nup98 dissociation from", "nup98 dissociation from the", "dissociation from the npc", "the npc laurell", "npc laurell et", "laurell et al. 2011", "et al. 2011 .", "al. 2011 . while", "2011 . while the", ". while the phosphorylation", "while the phosphorylation of", "the phosphorylation of nup98", "by cdk1 and nek6/7", "cdk1 and nek6/7 is", "and nek6/7 is likely", "nek6/7 is likely to", "is likely to occur", "likely to occur simultaneously", "occur simultaneously cdk1", "simultaneously cdk1 and", "cdk1 and nek6/7 mediated", "and nek6/7 mediated phosphorylations", "nek6/7 mediated phosphorylations are", "mediated phosphorylations are shown", "phosphorylations are shown as", "are shown as separate", "shown as separate events", "events for", "nuclear envelope breakdown in mitosis", "envelope breakdown in mitosis involves", "breakdown in mitosis involves permeabilization", "in mitosis involves permeabilization of", "mitosis involves permeabilization of the", "involves permeabilization of the nuclear", "permeabilization of the nuclear envelope", "of the nuclear envelope through", "the nuclear envelope through disassembly", "nuclear envelope through disassembly of", "envelope through disassembly of the", "through disassembly of the nuclear", "disassembly of the nuclear pore", "of the nuclear pore complex", "npc reviewed by", "reviewed by guttinger et al.", "by guttinger et al. 2009", "guttinger et al. 2009 .", "et al. 2009 . nucleoporin", "al. 2009 . nucleoporin nup98", ". nucleoporin nup98 located", "nucleoporin nup98 located at", "nup98 located at both", "located at both the cytoplasmic", "at both the cytoplasmic and", "both the cytoplasmic and the", "the cytoplasmic and the nucleoplasmic", "cytoplasmic and the nucleoplasmic side", "and the nucleoplasmic side of", "the nucleoplasmic side of the", "nucleoplasmic side of the npc", "of the npc griffis", "the npc griffis et", "npc griffis et al.", "al. 2003 and", "2003 and involved", "and involved in the formation", "involved in the formation of", "in the formation of the", "the formation of the transport", "formation of the transport barrier", "of the transport barrier through", "the transport barrier through its", "transport barrier through its fg", "through its fg phenylalanine", "its fg phenylalanine glycine", "phenylalanine glycine repeats that", "glycine repeats that protrude", "repeats that protrude into the", "that protrude into the central", "protrude into the central cavity", "into the central cavity of", "the central cavity of the", "central cavity of the npc", "of the npc hulsmann", "the npc hulsmann et", "npc hulsmann et al.", "al. 2012 is", "2012 is probably", "is probably the first nucleoporin", "probably the first nucleoporin that", "the first nucleoporin that dissociates", "first nucleoporin that dissociates from", "nucleoporin that dissociates from the", "that dissociates from the npc", "dissociates from the npc at", "from the npc at the", "the npc at the start", "npc at the start of", "at the start of mitotic", "the start of mitotic npc", "start of mitotic npc disassembly", "mitotic npc disassembly dultz", "npc disassembly dultz et", "disassembly dultz et al.", "dultz et al. 2008 .", "et al. 2008 . nup98", "al. 2008 . nup98 dissociation", "2008 . nup98 dissociation is", ". nup98 dissociation is triggered", "nup98 dissociation is triggered by", "dissociation is triggered by phosphorylation.", "is triggered by phosphorylation. phosphorylation", "triggered by phosphorylation. phosphorylation of", "by phosphorylation. phosphorylation of nup98", "phosphorylation. phosphorylation of nup98 by", "phosphorylation of nup98 by cdk1", "of nup98 by cdk1 and", "nup98 by cdk1 and nima", "by cdk1 and nima family", "cdk1 and nima family kinases", "and nima family kinases nek6", "nima family kinases nek6 and/or", "family kinases nek6 and/or nek7", "kinases nek6 and/or nek7 is", "nek6 and/or nek7 is needed", "and/or nek7 is needed for", "nek7 is needed for nup98", "is needed for nup98 dissociation", "needed for nup98 dissociation from", "for nup98 dissociation from the", "nup98 dissociation from the npc", "from the npc laurell", "the npc laurell et", "npc laurell et al.", "laurell et al. 2011 .", "et al. 2011 . while", "al. 2011 . while the", "2011 . while the phosphorylation", ". while the phosphorylation of", "while the phosphorylation of nup98", "the phosphorylation of nup98 by", "nup98 by cdk1 and nek6/7", "by cdk1 and nek6/7 is", "cdk1 and nek6/7 is likely", "and nek6/7 is likely to", "nek6/7 is likely to occur", "is likely to occur simultaneously", "to occur simultaneously cdk1", "occur simultaneously cdk1 and", "simultaneously cdk1 and nek6/7", "cdk1 and nek6/7 mediated phosphorylations", "and nek6/7 mediated phosphorylations are", "nek6/7 mediated phosphorylations are shown", "mediated phosphorylations are shown as", "phosphorylations are shown as separate", "are shown as separate events", "separate events for", "events for clarity" ] }, { "record_id": "GLY_000594_1_272", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3322077", "r hsa", "hsa 3322077", "r hsa 3322077" ] }, { "record_id": "GLY_000594_1_272", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycogen synthesis", "a highly", "highly branched", "branched glucose", "glucose polymer", "is formed", "formed and", "and broken", "broken down", "down in", "in most", "most human", "human tissues", "but is", "is most", "most abundant", "abundant in", "in liver", "liver and", "and muscle", "where it", "it serves", "serves as", "as a", "a major", "major stored", "stored fuel.", "fuel. glycogen", "glycogen metabolism", "metabolism has", "has been", "been studied", "studied in", "most detail", "detail in", "in muscle", "although considerable", "considerable experimental", 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all", "2011

all c", "

all c flip", "flip proteins carry", "proteins carry two", "carry two deds", "two deds at", "deds at their", "at their n", "their n termini", "termini which", "which can bind", "can bind fadd", "bind fadd and", "fadd and procaspase", "and procaspase 8.", "procaspase 8. in", "8. in addition", "in addition to", "addition to two", "to two deds", "deds flip", "l contains", "contains a large", "large p20", "p20 and", "and a small", "small p12", "p12 caspase", "caspase like domain", "like domain without", "domain without catalytic", "without catalytic activity.", "catalytic activity. flip", "activity. flip s", "s and", "and flip r", "r consist", "consist of two", "of two deds", "two deds and", "deds and a", "a small c", "small c terminus.", "c terminus. depending", "terminus. depending on", "depending on its", "on its level", "its level of", "level of expression", "of expression flip", "expression flip l", "l may", "may function as", "function as an", "as an anti", "an anti apoptotic", "anti apoptotic or", "apoptotic or pro", "or pro apoptotic", "pro apoptotic factor", "factor while", "while flip s", "r protect", "protect cells from", "cells from apoptosis", "from apoptosis by", "apoptosis by blocking", "by blocking the", "blocking the processing", "the processing of", "processing of caspase", "of caspase 8", "caspase 8 at", "8 at the", "at the receptor", "the receptor level", "level scaffidi", "2005 toivonen", "toivonen ht et", "ht et al.", "2011 fricker", "fricker n et", "n et al.", "et al. 2010", "al. 2010 .", "flip proteins casp8", "proteins casp8 and", "casp8 and fadd like", "and fadd like apoptosis", "fadd like apoptosis regulators", "like apoptosis regulators or", "apoptosis regulators or c", "regulators or c flice", "or c flice inhibitory", "c flice inhibitory proteins", "inhibitory proteins are", "proteins are death", "are death effector domain", "effector domain ded", "ded containing proteins", "containing proteins that are", "proteins that are recruited", "that are recruited to", "are recruited to the", "recruited to the death", "to the death inducing", "the death inducing signaling", "death inducing signaling complex", "signaling complex disc", "disc to regulate", "to regulate activation of", "regulate activation of caspases", "activation of caspases 8.", "of caspases 8. three", "caspases 8. three out", "8. three out of", "three out of 13", "out of 13 distinct", "of 13 distinct spliced", "13 distinct spliced variants", "distinct spliced variants of", "spliced variants of c", "variants of c flip", "of c flip had", "c flip had been", "flip had been found", "had been found to", "been found to be", "found to be expressed", "to be expressed at", "be expressed at the", "expressed at the protein", "at the protein level", "protein level the", "level the 26", "the 26 kda short", "26 kda short form", "kda short form flip", "short form flip s", "s the", "the 24 kda form", "24 kda form flip", "kda form flip r", "r and", "and the 55 kda", "the 55 kda long", "55 kda long form", "kda long form flip", "long form flip l", "l irmler", "irmler m et al.", "m et al. 1997", "al. 1997 shu", "1997 shu hb", "shu hb et al.", "hb et al. 1997", "al. 1997 srinivasula", "1997 srinivasula sm", "srinivasula sm et al.", "sm et al. 1997", "al. 1997 scaffidi", "1997 scaffidi c", "scaffidi c et al.", "c et al. 1999", "al. 1999 golks", "1999 golks a", "golks a et al.", "a et al. 2005", "al. 2005 haag", "2005 haag c", "haag c et al.", "c et al. 2011", "et al. 2011

all", "al. 2011

all c", "2011

all c flip", "

all c flip proteins", "c flip proteins carry", "flip proteins carry two", "proteins carry two deds", "carry two deds at", "two deds at their", "deds at their n", "at their n termini", "n termini which", "termini which can", "which can bind fadd", "can bind fadd and", "bind fadd and procaspase", "fadd and procaspase 8.", "and procaspase 8. in", "procaspase 8. in addition", "8. in addition to", "in addition to two", "addition to two deds", "two deds flip", "deds flip l", "flip l contains", "l contains a", "a large p20", "p20 and a", "a small p12", "p12 caspase like", "caspase like domain without", "like domain without catalytic", "domain without catalytic activity.", "without catalytic activity. flip", "catalytic activity. flip s", "flip s and", "s and flip", "flip r consist", "r consist of", "consist of two deds", "of two deds and", "two deds and a", "deds and a small", "and a small c", "a small c terminus.", "small c terminus. depending", "c terminus. depending on", "terminus. depending on its", "depending on its level", "on its level of", "its level of expression", "level of expression flip", "of expression flip l", "flip l may", "l may function", "may function as an", "function as an anti", "as an anti apoptotic", "an anti apoptotic or", "anti apoptotic or pro", "apoptotic or pro apoptotic", "or pro apoptotic factor", "apoptotic factor while", "factor while flip", "flip r protect", "r protect cells", "protect cells from apoptosis", "cells from apoptosis by", "from apoptosis by blocking", "apoptosis by blocking the", "by blocking the processing", "blocking the processing of", "the processing of caspase", "processing of caspase 8", "of caspase 8 at", "caspase 8 at the", "8 at the receptor", "at the receptor level", "receptor level scaffidi", "level scaffidi c", "al. 2005 toivonen", "2005 toivonen ht", "toivonen ht et al.", "ht et al. 2011", "al. 2011 fricker", "2011 fricker n", "fricker n et al.", "n et al. 2010", "et al. 2010 .", "c flip proteins casp8", "flip proteins casp8 and", "proteins casp8 and fadd", "casp8 and fadd like apoptosis", "and fadd like apoptosis regulators", "fadd like apoptosis regulators or", "like apoptosis regulators or c", "apoptosis regulators or c flice", "regulators or c flice inhibitory", "or c flice inhibitory proteins", "flice inhibitory proteins are", "inhibitory proteins are death", "proteins are death effector", "death effector domain ded", "domain ded containing", "ded containing proteins that", "containing proteins that are recruited", "proteins that are recruited to", "that are recruited to the", "are recruited to the death", "recruited to the death inducing", "to the death inducing signaling", "the death inducing signaling complex", "inducing signaling complex disc", "complex disc to", "disc to regulate activation", "to regulate activation of caspases", "regulate activation of caspases 8.", "activation of caspases 8. three", "of caspases 8. three out", "caspases 8. three out of", "8. three out of 13", "three out of 13 distinct", "out of 13 distinct spliced", "of 13 distinct spliced variants", "13 distinct spliced variants of", "distinct spliced variants of c", "spliced variants of c flip", "variants of c flip had", "of c flip had been", "c flip had been found", "flip had been found to", "had been found to be", "been found to be expressed", "found to be expressed at", "to be expressed at the", "be expressed at the protein", "expressed at the protein level", "the protein level the", "protein level the 26", "level the 26 kda", "the 26 kda short form", "26 kda short form flip", "kda short form flip s", "flip s the", "s the 24", "the 24 kda form flip", "24 kda form flip r", "flip r and", "r and the", "and the 55 kda long", "the 55 kda long form", "55 kda long form flip", "kda long form flip l", "flip l irmler", "l irmler m", "irmler m et al. 1997", "et al. 1997 shu", "al. 1997 shu hb", "1997 shu hb et", "shu hb et al. 1997", "et al. 1997 srinivasula", "al. 1997 srinivasula sm", "1997 srinivasula sm et", "srinivasula sm et al. 1997", "et al. 1997 scaffidi", "al. 1997 scaffidi c", "1997 scaffidi c et", "scaffidi c et al. 1999", "et al. 1999 golks", "al. 1999 golks a", "1999 golks a et", "golks a et al. 2005", "et al. 2005 haag", "al. 2005 haag c", "2005 haag c et", "haag c et al. 2011", "c et al. 2011

all", "et al. 2011

all c", "al. 2011

all c flip", "2011

all c flip proteins", "

all c flip proteins carry", "c flip proteins carry two", "flip proteins carry two deds", "proteins carry two deds at", "carry two deds at their", "two deds at their n", "deds at their n termini", "their n termini which", "n termini which can", "termini which can bind", "which can bind fadd and", "can bind fadd and procaspase", "bind fadd and procaspase 8.", "fadd and procaspase 8. in", "and procaspase 8. in addition", "procaspase 8. in addition to", "8. in addition to two", "in addition to two deds", "to two deds flip", "two deds flip l", "flip l contains a", "l contains a large", "contains a large p20", "large p20 and", "p20 and a small", "and a small p12", "small p12 caspase", "p12 caspase like domain", "caspase like domain without catalytic", "like domain without catalytic activity.", "domain without catalytic activity. flip", "without catalytic activity. flip s", "activity. flip s and", "flip s and flip", "s and flip r", "and flip r consist", "flip r consist of", "r consist of two", "consist of two deds and", "of two deds and a", "two deds and a small", "deds and a small c", "and a small c terminus.", "a small c terminus. depending", "small c terminus. depending on", "c terminus. depending on its", "terminus. depending on its level", "depending on its level of", "on its level of expression", "its level of expression flip", "level of expression flip l", "expression flip l may", "flip l may function", "l may function as", "may function as an anti", "function as an anti apoptotic", "as an anti apoptotic or", "an anti apoptotic or pro", "anti apoptotic or pro apoptotic", "apoptotic or pro apoptotic factor", "pro apoptotic factor while", "apoptotic factor while flip", "factor while flip s", "while flip s and", "and flip r protect", "flip r protect cells", "r protect cells from", "protect cells from apoptosis by", "cells from apoptosis by blocking", "from apoptosis by blocking the", "apoptosis by blocking the processing", "by blocking the processing of", "blocking the processing of caspase", "the processing of caspase 8", "processing of caspase 8 at", "of caspase 8 at the", "caspase 8 at the receptor", "8 at the receptor level", "the receptor level scaffidi", "receptor level scaffidi c", "level scaffidi c et", "et al. 2005 toivonen", "al. 2005 toivonen ht", "2005 toivonen ht et", "toivonen ht et al. 2011", "et al. 2011 fricker", "al. 2011 fricker n", "2011 fricker n et", "fricker n et al. 2010", "n et al. 2010 ." ] }, { "record_id": "GLY_000594_1_274", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3371453", "r hsa", "hsa 3371453", "r hsa 3371453" ] }, { "record_id": "GLY_000594_1_274", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of hsf1", "hsf1 mediated", "mediated heat", "heat shock", "shock response", "regulation of hsf1", "of hsf1 mediated", "hsf1 mediated heat", "mediated heat shock", "heat shock response", "regulation of hsf1 mediated", "of hsf1 mediated heat", "hsf1 mediated heat shock", "mediated heat shock response", "regulation of hsf1 mediated heat", "of hsf1 mediated heat shock", "hsf1 mediated heat shock response", "the ability", "ability of", "hsf1 to", "to respond", "respond to", "to cellular", "cellular stresses", "stresses is", "is under", "under negative", "negative regulation", "regulation by", "by chaperones", "modulation of", "of nucleocytoplasmic", "nucleocytoplasmic shuttling", "post translational", "translational modifications", "modifications and", "and transition", "transition from", "from monomeric", "monomeric to", "to trimeric", "trimeric state.", "the ability of", "ability of hsf1", "of hsf1 to", "hsf1 to respond", "to respond to", "respond to cellular", "to cellular stresses", "cellular stresses is", "stresses is under", "is under negative", "under negative regulation", "negative regulation by", "regulation by chaperones", "chaperones modulation", "modulation of nucleocytoplasmic", "of nucleocytoplasmic shuttling", "shuttling post", "post translational modifications", "translational modifications and", "modifications and transition", "and transition from", "transition from monomeric", "from monomeric to", "monomeric to trimeric", "to trimeric state.", "the ability of hsf1", "ability of hsf1 to", "of hsf1 to respond", "hsf1 to respond to", "to respond to cellular", "respond to cellular stresses", "to cellular stresses is", "cellular stresses is under", "stresses is under negative", "is under negative regulation", "under negative regulation by", "negative regulation by chaperones", "by chaperones modulation", "chaperones modulation of", "modulation of nucleocytoplasmic shuttling", "nucleocytoplasmic shuttling post", "shuttling post translational", "post translational modifications and", "translational modifications and transition", "modifications and transition from", "and transition from monomeric", "transition from monomeric to", "from monomeric to trimeric", "monomeric to trimeric state.", "the ability of hsf1 to", "ability of hsf1 to respond", "of hsf1 to respond to", "hsf1 to respond to cellular", "to respond to cellular stresses", "respond to cellular stresses is", "to cellular stresses is under", "cellular stresses is under negative", "stresses is under negative regulation", "is under negative regulation by", "under negative regulation by chaperones", "regulation by chaperones modulation", "by chaperones modulation of", "chaperones modulation of nucleocytoplasmic", "of nucleocytoplasmic shuttling post", "nucleocytoplasmic shuttling post translational", "shuttling post translational modifications", "post translational modifications and transition", "translational modifications and transition from", "modifications and transition from monomeric", "and transition from monomeric to", "transition from monomeric to trimeric", "from monomeric to trimeric state." ] }, { "record_id": "GLY_000594_1_275", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3371497", "r hsa", "hsa 3371497", "r hsa 3371497" ] }, { "record_id": "GLY_000594_1_275", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hsp90 chaperone", "chaperone cycle", "cycle for", "for steroid", "steroid hormone", "hormone receptors", "in the", "the presence", "presence of", "of ligand", "hsp90 chaperone cycle", "chaperone cycle for", "cycle for steroid", "for steroid hormone", "steroid hormone receptors", "receptors shr", "shr in", "in the presence", "the presence of", "presence of ligand", "hsp90 chaperone cycle for", "chaperone cycle for steroid", "cycle for steroid hormone", "for steroid hormone receptors", "hormone receptors shr", "shr in the", "in the presence of", "the presence of ligand", "hsp90 chaperone cycle for steroid", "chaperone cycle for steroid hormone", "cycle for steroid hormone receptors", "steroid hormone receptors shr", "receptors shr in", "shr in the presence", "in the presence of ligand", "are transcription", "transcription factors", "factors that", "that become", "become activated", "activated upon", "upon sensing", "sensing steroid", "steroid hormones", "hormones such", "such as", "as glucocorticoids", "or estrogen", "escriva et", "et al", "al 2000", "griekspoor a", "a et", "et al.", "al. 2007", "eick gn", "gn &", "& thornton", "thornton jw.", "jw. 2011", "2011 .", ". depending", "depending on", "on shr", "shr type", "type and", "and the", "they show", "show different", "different subcellular", "subcellular localizations.", "localizations. whereas", "whereas both", "both unliganded", "unliganded and", "and liganded", "liganded estrogen", "estrogen receptors", "eralpha and", "and erbeta", "are predominantly", "predominantly nuclear", "unliganded glucocorticoid", "and androgen", "androgen receptors", "are mostly", "mostly located", "located in", "the cytoplasm", "cytoplasm and", "and completely", "completely translocate", "translocate to", "to the", "the nucleus", "nucleus only", "only after", "after binding", "binding hormone", "htun h", "h et", "al. 1999", "stenoien d", "d et", "al. 2000", "tyagi rk", "rk et", "cadepond f", "f et", "al. 1992", "jewell cm", "cm et", "al. 1995", "kumar s", "s et", "al. 2006", "2006 .", ". the", "the unliganded", "unliganded mineralocorticoid", "mineralocorticoid receptor", "is partially", "partially cytoplasmic", "cytoplasmic but", "but can", "can be", "be found", "found in", "in nucleus", "nucleus in", "the ligand", "ligand bound", "bound or", "or ligand", "ligand free", "free form", "nishi m", "m &", "& kawata", "kawata m", "m 2007", "2007 .", "the progesterone", "progesterone receptor", "exists in", "in two", "two forms", "pra and", "and prb", "with different", "different ratios", "ratios of", "of nuclear", "nuclear versus", "versus cytoplasmic", "cytoplasmic localization", "localization of", "of the", "unliganded receptor.", "receptor. in", "in most", "most cell", "cell contexts", "the pra", "pra isoform", "isoform is", "is a", "a repressor", "repressor of", "the shorter", "shorter prb", "prb isoform", "and without", "without hormone", "hormone induction", "induction it", "it is", "is mostly", "whereas prb", "prb distributes", "distributes both", "both in", "nucleus and", "and in", "lim cs", "cs et", ". in", "the absence", "absence of", "members of", "the steroid", "steroid receptor", "receptor family", "family remain", "remain sequestered", "sequestered in", "cytoplasm and/or", "and/or nucleus", "the complex", "complex with", "with proteins", "proteins of", "of hsp70/hsp90", "hsp70/hsp90 chaperone", "chaperone machinery", "pratt wb", "wb &", "& dittmar", "dittmar kd1998", "kd1998 .", "the highly", "highly dynamic", "dynamic atp", "atp dependent", "dependent interactions", "interactions of", "of shrs", "shrs with", "with hsp90", "hsp90 complexes", "complexes regulate", "regulate shr", "shr cellular", "cellular location", "protein stability", "competency to", "to bind", "bind steroid", "hormones and", "and transcriptional", "transcriptional activity", "echeverria pc", "pc &", "& picard", "picard d", "d 2010", "2010 .", ". understanding", "understanding the", "the mechanism", "mechanism of", "of atpase", "atpase activity", "activity of", "of hsp90", "hsp90 is", "mostly based", "based on", "on structural", "structural and", "and functional", "functional studies", "studies of", "the saccharomyces", "saccharomyces cerevisiae", "cerevisiae hsp90", "meyer p", "p et", "al. 2003", "ali mm", "mm et", "prodromou c", "c et", "c 2012", "2012 .", "the atpase", "atpase cycle", "cycle of", "of human", "human hsp90", "is less", "less well", "well understood", "however several", "several studies", "studies suggest", "suggest that", "that the", "the underlying", "underlying enzymatic", "enzymatic mechanisms", "mechanisms and", "and a", "a set", "set of", "of conformational", "conformational changes", "changes that", "that accompany", "accompany the", "cycle are", "are highly", "highly similar", "similar in", "in both", "both species", "richter k", "k et", "al. 2008", "vaughan ck", "ck et", "al. 2009", "2009 .", ". nascent", "nascent shr", "shr proteins", "proteins are", "are chaperoned", "chaperoned by", "by hsp70", "hsp70 and", "and hsp40", "hsp40 to", "to hsp90", "hsp90 cycle", "cycle via", "via stip1", "and its", "its tpr", "tpr domains", "hern\u00e1ndez mp", "mp et", "al. 2002a", "2002a b", "echeverriapc &", "li j", "j et", "al. 2011", "the atp", "atp bound", "bound form", "form of", "hsp90 leads", "leads to", "the displacement", "displacement of", "of stip1", "stip1 by", "by immunophilins", "immunophilins fkbp5", "fkbp5 or", "or fkbp4", "fkbp4 resulting", "resulting in", "in conformational", "that allow", "allow efficient", "efficient hormone", "hormone binding", ". ptges3", "binds to", "hsp90 complex", "complex finally", "finally stabilizing", "stabilizing it", "it in", "the conformation", "conformation with", "with a", "a high", "high hormone", "binding affinity.", "affinity. after", "after hydrolysis", "hydrolysis of", "of atp", "atp the", "the hormone", "hormone bound", "bound shr", "shr is", "is released", "released from", "from hsp90", "hsp90 complex.", "complex. the", "the cytosolic", "cytosolic hormone", "shr can", "be transported", "transported to", "nucleus by", "by several", "several import", "import pathways", "pathways such", "as the", "the dynein", "dynein based", "based nuclear", "nuclear transport", "transport along", "along microtubules", "microtubules involving", "involving the", "the transport", "transport of", "the entire", "entire hsp90", "complex or", "or nuclear", "nuclear localization", "localization signals", "mediated nuclear", "nuclear targeting", "targeting by", "by importins", ". it", "is worth", "worth noting", "noting that", "that gr", "gr importin", "importin interactions", "interactions can", "be ligand", "ligand dependent", "dependent or", "or independent", "freedman &", "& yamamoto", "yamamoto 2004", "picard &", "yamamoto 1987", "1987 .", "nucleus ligand", "ligand activated", "activated shr", "shr dimerizes", "binds specific", "specific sequences", "sequences in", "the dna", "called hormone", "hormone responsive", "responsive elements", "and recruits", "recruits a", "a number", "number of", "of coregulators", "coregulators that", "that facilitate", "facilitate gene", "gene transcription.", "transcription. nuclear", "localization is", "is essential", "essential for", "for shrs", "shrs to", "to transactivate", "transactivate their", "their target", "target genes", "but the", "the same", "same receptors", "receptors also", "also possess", "possess non", "non genomic", "genomic functions", "functions in", "the cytoplasm.

the", "cytoplasm.

the reactome", "reactome module", "module describes", "describes the", "atpase driven", "driven conformational", "conformational cycle", "hsp90 that", "that regulates", "regulates ligand", "dependent activation", "activation of", "of shrs.", "shr are", "are transcription factors", "transcription factors that", "factors that become", "that become activated", "become activated upon", "activated upon sensing", "upon sensing steroid", "sensing steroid hormones", "steroid hormones such", "hormones such as", "such as glucocorticoids", "glucocorticoids mineralocorticoids", "mineralocorticoids progesterone", "progesterone androgens", "androgens or", "estrogen escriva", "escriva et al", "et al 2000", "2000 griekspoor", "griekspoor a et", "a et al.", "et al. 2007", "2007 eick", "eick gn &", "gn & thornton", "& thornton jw.", "thornton jw. 2011", "jw. 2011 .", "2011 . depending", ". depending on", "depending on shr", "on shr type", "shr type and", "type and the", "and the presence", "ligand they", "they show different", "show different subcellular", "different subcellular localizations.", "subcellular localizations. whereas", "localizations. whereas both", "whereas both unliganded", "both unliganded and", "unliganded and liganded", "and liganded estrogen", "liganded estrogen receptors", "receptors eralpha", "eralpha and erbeta", "erbeta are", "are predominantly nuclear", "nuclear unliganded", "glucocorticoid gr", "gr and", "and androgen receptors", "receptors ar", "ar are", "are mostly located", "mostly located in", "located in the", "in the cytoplasm", "the cytoplasm and", "cytoplasm and completely", "and completely translocate", "completely translocate to", "translocate to the", "to the nucleus", "the nucleus only", "nucleus only after", "only after binding", "after binding hormone", "hormone htun", "htun h et", "h et al.", "et al. 1999", "1999 stenoien", "stenoien d et", "d et al.", "et al. 2000", "2000 tyagi", "tyagi rk et", "rk et al.", "2000 cadepond", "cadepond f et", "f et al.", "et al. 1992", "1992 jewell", "jewell cm et", "cm et al.", "et al. 1995", "1995 kumar", "kumar s et", "s et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the unliganded", "the unliganded mineralocorticoid", "unliganded mineralocorticoid receptor", "receptor mr", "mr is", "is partially cytoplasmic", "partially cytoplasmic but", "cytoplasmic but can", "but can be", "can be found", "be found in", "found in nucleus", "in nucleus in", "nucleus in the", "in the ligand", "the ligand bound", "ligand bound or", "bound or ligand", "or ligand free", "ligand free form", "form nishi", "nishi m &", "m & kawata", "& kawata m", "kawata m 2007", "m 2007 .", "2007 . the", ". the progesterone", "the progesterone receptor", "receptor pr", "pr exists", "exists in two", "in two forms", "forms pra", "pra and prb", "prb with", "with different ratios", "different ratios of", "ratios of nuclear", "of nuclear versus", "nuclear versus cytoplasmic", "versus cytoplasmic localization", "cytoplasmic localization of", "localization of the", "of the unliganded", "the unliganded receptor.", "unliganded receptor. in", "receptor. in most", "in most cell", "most cell contexts", "contexts the", "the pra isoform", "pra isoform is", "isoform is a", "is a repressor", "a repressor of", "repressor of the", "of the shorter", "the shorter prb", "shorter prb isoform", "isoform and", "and without hormone", "without hormone induction", "hormone induction it", "induction it is", "it is mostly", "is mostly located", "in the nucleus", "nucleus whereas", "whereas prb distributes", "prb distributes both", "distributes both in", "both in the", "the nucleus and", "nucleus and in", "and in the", "cytoplasm lim", "lim cs et", "cs et al.", "1999 griekspoor", "al. 2007 .", "2007 . in", ". in the", "in the absence", "the absence of", "absence of ligand", "ligand members", "members of the", "of the steroid", "the steroid receptor", "steroid receptor family", "receptor family remain", "family remain sequestered", "remain sequestered in", "sequestered in the", "the cytoplasm and/or", "cytoplasm and/or nucleus", "and/or nucleus in", "in the complex", "the complex with", "complex with proteins", "with proteins of", "proteins of hsp70/hsp90", "of hsp70/hsp90 chaperone", "hsp70/hsp90 chaperone machinery", "machinery pratt", "pratt wb &", "wb & dittmar", "& dittmar kd1998", "dittmar kd1998 .", "kd1998 . the", ". the highly", "the highly dynamic", "highly dynamic atp", "dynamic atp dependent", "atp dependent interactions", "dependent interactions of", "interactions of shrs", "of shrs with", "shrs with hsp90", "with hsp90 complexes", "hsp90 complexes regulate", "complexes regulate shr", "regulate shr cellular", "shr cellular location", "location protein", "stability competency", "competency to bind", "to bind steroid", "bind steroid hormones", "steroid hormones and", "hormones and transcriptional", "and transcriptional activity", "activity echeverria", "echeverria pc &", "pc & picard", "& picard d", "picard d 2010", "d 2010 .", "2010 . understanding", ". understanding the", "understanding the mechanism", "the mechanism of", "mechanism of atpase", "of atpase activity", "atpase activity of", "activity of hsp90", "of hsp90 is", "hsp90 is mostly", "is mostly based", "mostly based on", "based on structural", "on structural and", "structural and functional", "and functional studies", "functional studies of", "studies of the", "of the saccharomyces", "the saccharomyces cerevisiae", "saccharomyces cerevisiae hsp90", "cerevisiae hsp90 complexes", "complexes meyer", "meyer p et", "p et al.", "et al. 2003", "2003 2004", "2004 ali", "ali mm et", "mm et al.", "2006 prodromou", "prodromou c et", "c et al.", "2000 prodromou", "prodromou c 2012", "c 2012 .", "2012 . the", ". the atpase", "the atpase cycle", "atpase cycle of", "cycle of human", "of human hsp90", "human hsp90 is", "hsp90 is less", "is less well", "less well understood", "understood however", "however several studies", "several studies suggest", "studies suggest that", "suggest that the", "that the underlying", "the underlying enzymatic", "underlying enzymatic mechanisms", "enzymatic mechanisms and", "mechanisms and a", "and a set", "a set of", "set of conformational", "of conformational changes", "conformational changes that", "changes that accompany", "that accompany the", "accompany the atpase", "atpase cycle are", "cycle are highly", "are highly similar", "highly similar in", "similar in both", "in both species", "species richter", "richter k et", "k et al.", "et al. 2008", "2008 vaughan", "vaughan ck et", "ck et al.", "et al. 2009", "al. 2009 .", "2009 . nascent", ". nascent shr", "nascent shr proteins", "shr proteins are", "proteins are chaperoned", "are chaperoned by", "chaperoned by hsp70", "by hsp70 and", "hsp70 and hsp40", "and hsp40 to", "hsp40 to hsp90", "to hsp90 cycle", "hsp90 cycle via", "cycle via stip1", "stip1 hop", "and its tpr", "its tpr domains", "hern\u00e1ndez mp et", "mp et al.", "et al. 2002a", "al. 2002a b", "b echeverriapc", "echeverriapc & picard", "2010 li", "li j et", "j et al.", "et al. 2011", "al. 2011 .", "2011 . the", ". the atp", "the atp bound", "atp bound form", "bound form of", "form of hsp90", "of hsp90 leads", "hsp90 leads to", "leads to the", "to the displacement", "the displacement of", "displacement of stip1", "of stip1 by", "stip1 by immunophilins", "by immunophilins fkbp5", "immunophilins fkbp5 or", "fkbp5 or fkbp4", "or fkbp4 resulting", "fkbp4 resulting in", "resulting in conformational", "in conformational changes", "changes that allow", "that allow efficient", "allow efficient hormone", "efficient hormone binding", "binding li", "2011 . ptges3", "ptges3 p23", "p23 binds", "binds to hsp90", "to hsp90 complex", "hsp90 complex finally", "complex finally stabilizing", "finally stabilizing it", "stabilizing it in", "it in the", "in the conformation", "the conformation with", "conformation with a", "with a high", "a high hormone", "high hormone binding", "hormone binding affinity.", "binding affinity. after", "affinity. after hydrolysis", "after hydrolysis of", "hydrolysis of atp", "of atp the", "atp the hormone", "the hormone bound", "hormone bound shr", "bound shr is", "shr is released", "is released from", "released from hsp90", "from hsp90 complex.", "hsp90 complex. the", "complex. the cytosolic", "the cytosolic hormone", "cytosolic hormone bound", "bound shr can", "shr can be", "can be transported", "be transported to", "transported to the", "the nucleus by", "nucleus by several", "by several import", "several import pathways", "import pathways such", "pathways such as", "such as the", "as the dynein", "the dynein based", "dynein based nuclear", "based nuclear transport", "nuclear transport along", "transport along microtubules", "along microtubules involving", "microtubules involving the", "involving the transport", "the transport of", "transport of the", "of the entire", "the entire hsp90", "entire hsp90 complex", "hsp90 complex or", "complex or nuclear", "or nuclear localization", "nuclear localization signals", "signals nls", "nls mediated", "mediated nuclear targeting", "nuclear targeting by", "targeting by importins", "importins tyagi", "2006 . it", ". it is", "it is worth", "is worth noting", "worth noting that", "noting that gr", "that gr importin", "gr importin interactions", "importin interactions can", "interactions can be", "can be ligand", "be ligand dependent", "ligand dependent or", "dependent or independent", "independent freedman", "freedman & yamamoto", "& yamamoto 2004", "2004 picard", "picard & yamamoto", "& yamamoto 1987", "yamamoto 1987 .", "1987 . in", "the nucleus ligand", "nucleus ligand activated", "ligand activated shr", "activated shr dimerizes", "dimerizes binds", "binds specific sequences", "specific sequences in", "sequences in the", "in the dna", "dna called", "called hormone responsive", "hormone responsive elements", "elements hre", "and recruits a", "recruits a number", "a number of", "number of coregulators", "of coregulators that", "coregulators that facilitate", "that facilitate gene", "facilitate gene transcription.", "gene transcription. nuclear", "transcription. nuclear localization", "nuclear localization is", "localization is essential", "is essential for", "essential for shrs", "for shrs to", "shrs to transactivate", "to transactivate their", "transactivate their target", "their target genes", "genes but", "but the same", "the same receptors", "same receptors also", "receptors also possess", "also possess non", "possess non genomic", "non genomic functions", "genomic functions in", "functions in the", "in the cytoplasm.

the", "the cytoplasm.

the reactome", "cytoplasm.

the reactome module", "reactome module describes", "module describes the", "describes the atpase", "the atpase driven", "atpase driven conformational", "driven conformational cycle", "conformational cycle of", "cycle of hsp90", "of hsp90 that", "hsp90 that regulates", "that regulates ligand", "regulates ligand dependent", "ligand dependent activation", "dependent activation of", "activation of shrs.", "shr are transcription", "are transcription factors that", "transcription factors that become", "factors that become activated", "that become activated upon", "become activated upon sensing", "activated upon sensing steroid", "upon sensing steroid hormones", "sensing steroid hormones such", "steroid hormones such as", "hormones such as glucocorticoids", "as glucocorticoids mineralocorticoids", "androgens or estrogen", "or estrogen escriva", "estrogen escriva et", "escriva et al 2000", "al 2000 griekspoor", "2000 griekspoor a", "griekspoor a et al.", "a et al. 2007", "al. 2007 eick", "2007 eick gn", "eick gn & thornton", "gn & thornton jw.", "& thornton jw. 2011", "thornton jw. 2011 .", "jw. 2011 . depending", "2011 . depending on", ". depending on shr", "depending on shr type", "on shr type and", "shr type and the", "type and the presence", "and the presence of", "of ligand they", "ligand they show", "they show different subcellular", "show different subcellular localizations.", "different subcellular localizations. whereas", "subcellular localizations. whereas both", "localizations. whereas both unliganded", "whereas both unliganded and", "both unliganded and liganded", "unliganded and liganded estrogen", "and liganded estrogen receptors", "estrogen receptors eralpha", "receptors eralpha and", "and erbeta are", "erbeta are predominantly", "predominantly nuclear unliganded", "nuclear unliganded glucocorticoid", "unliganded glucocorticoid gr", "gr and androgen", "androgen receptors ar", "ar are mostly", "are mostly located in", "mostly located in the", "located in the cytoplasm", "in the cytoplasm and", "the cytoplasm and completely", "cytoplasm and completely translocate", "and completely translocate to", "completely translocate to the", "translocate to the nucleus", "to the nucleus only", "the nucleus only after", "nucleus only after binding", "only after binding hormone", "binding hormone htun", "hormone htun h", "htun h et al.", "h et al. 1999", "al. 1999 stenoien", "1999 stenoien d", "stenoien d et al.", "d et al. 2000", "al. 2000 tyagi", "2000 tyagi rk", "tyagi rk et al.", "rk et al. 2000", "al. 2000 cadepond", "2000 cadepond f", "cadepond f et al.", "f et al. 1992", "al. 1992 jewell", "1992 jewell cm", "jewell cm et al.", "cm et al. 1995", "al. 1995 kumar", "1995 kumar s", "kumar s et al.", "s et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the unliganded", ". the unliganded mineralocorticoid", "the unliganded mineralocorticoid receptor", "mineralocorticoid receptor mr", "mr is partially", "is partially cytoplasmic but", "partially cytoplasmic but can", "cytoplasmic but can be", "but can be found", "can be found in", "be found in nucleus", "found in nucleus in", "in nucleus in the", "nucleus in the ligand", "in the ligand bound", "the ligand bound or", "ligand bound or ligand", "bound or ligand free", "or ligand free form", "free form nishi", "form nishi m", "nishi m & kawata", "m & kawata m", "& kawata m 2007", "kawata m 2007 .", "m 2007 . the", "2007 . the progesterone", ". the progesterone receptor", "progesterone receptor pr", "pr exists in", "exists in two forms", "two forms pra", "forms pra and", "and prb with", "prb with different", "with different ratios of", "different ratios of nuclear", "ratios of nuclear versus", "of nuclear versus cytoplasmic", "nuclear versus cytoplasmic localization", "versus cytoplasmic localization of", "cytoplasmic localization of the", "localization of the unliganded", "of the unliganded receptor.", "the unliganded receptor. in", "unliganded receptor. in most", "receptor. in most cell", "in most cell contexts", "cell contexts the", "contexts the pra", "the pra isoform is", "pra isoform is a", "isoform is a repressor", "is a repressor of", "a repressor of the", "repressor of the shorter", "of the shorter prb", "the shorter prb isoform", "prb isoform and", "isoform and without", "and without hormone induction", "without hormone induction it", "hormone induction it is", "induction it is mostly", "it is mostly located", "is mostly located in", "located in the nucleus", "the nucleus whereas", "nucleus whereas prb", "whereas prb distributes both", "prb distributes both in", "distributes both in the", "both in the nucleus", "in the nucleus and", "the nucleus and in", "nucleus and in the", "and in the cytoplasm", "the cytoplasm lim", "cytoplasm lim cs", "lim cs et al.", "cs et al. 1999", "al. 1999 griekspoor", "1999 griekspoor a", "et al. 2007 .", "al. 2007 . in", "2007 . in the", ". in the absence", "in the absence of", "the absence of ligand", "of ligand members", "ligand members of", "members of the steroid", "of the steroid receptor", "the steroid receptor family", "steroid receptor family remain", "receptor family remain sequestered", "family remain sequestered in", "remain sequestered in the", "sequestered in the cytoplasm", "in the cytoplasm and/or", "the cytoplasm and/or nucleus", "cytoplasm and/or nucleus in", "and/or nucleus in the", "nucleus in the complex", "in the complex with", "the complex with proteins", "complex with proteins of", "with proteins of hsp70/hsp90", "proteins of hsp70/hsp90 chaperone", "of hsp70/hsp90 chaperone machinery", "chaperone machinery pratt", "machinery pratt wb", "pratt wb & dittmar", "wb & dittmar kd1998", "& dittmar kd1998 .", "dittmar kd1998 . the", "kd1998 . the highly", ". the highly dynamic", "the highly dynamic atp", "highly dynamic atp dependent", "dynamic atp dependent interactions", "atp dependent interactions of", "dependent interactions of shrs", "interactions of shrs with", "of shrs with hsp90", "shrs with hsp90 complexes", "with hsp90 complexes regulate", "hsp90 complexes regulate shr", "complexes regulate shr cellular", "regulate shr cellular location", "cellular location protein", "location protein stability", "protein stability competency", "stability competency to", "competency to bind steroid", "to bind steroid hormones", "bind steroid hormones and", "steroid hormones and transcriptional", "hormones and transcriptional activity", "transcriptional activity echeverria", "activity echeverria pc", "echeverria pc & picard", "pc & picard d", "& picard d 2010", "picard d 2010 .", "d 2010 . understanding", "2010 . understanding the", ". understanding the mechanism", "understanding the mechanism of", "the mechanism of atpase", "mechanism of atpase activity", "of atpase activity of", "atpase activity of hsp90", "activity of hsp90 is", "of hsp90 is mostly", "hsp90 is mostly based", "is mostly based on", "mostly based on structural", "based on structural and", "on structural and functional", "structural and functional studies", "and functional studies of", "functional studies of the", "studies of the saccharomyces", "of the saccharomyces cerevisiae", "the saccharomyces cerevisiae hsp90", "saccharomyces cerevisiae hsp90 complexes", "hsp90 complexes meyer", "complexes meyer p", "meyer p et al.", "p et al. 2003", "al. 2003 2004", "2004 ali mm", "ali mm et al.", "mm et al. 2006", "al. 2006 prodromou", "2006 prodromou c", "prodromou c et al.", "c et al. 2000", "al. 2000 prodromou", "2000 prodromou c", "prodromou c 2012 .", "c 2012 . the", "2012 . the atpase", ". the atpase cycle", "the atpase cycle of", "atpase cycle of human", "cycle of human hsp90", "of human hsp90 is", "human hsp90 is less", "hsp90 is less well", "is less well understood", "well understood however", "understood however several", "however several studies suggest", "several studies suggest that", "studies suggest that the", "suggest that the underlying", "that the underlying enzymatic", "the underlying enzymatic mechanisms", "underlying enzymatic mechanisms and", "enzymatic mechanisms and a", "mechanisms and a set", "and a set of", "a set of conformational", "set of conformational changes", "of conformational changes that", "conformational changes that accompany", "changes that accompany the", "that accompany the atpase", "accompany the atpase cycle", "the atpase cycle are", "atpase cycle are highly", "cycle are highly similar", "are highly similar in", "highly similar in both", "similar in both species", "both species richter", "species richter k", "richter k et al.", "k et al. 2008", "al. 2008 vaughan", "2008 vaughan ck", "vaughan ck et al.", "ck et al. 2009", "et al. 2009 .", "al. 2009 . nascent", "2009 . nascent shr", ". nascent shr proteins", "nascent shr proteins are", "shr proteins are chaperoned", "proteins are chaperoned by", "are chaperoned by hsp70", "chaperoned by hsp70 and", "by hsp70 and hsp40", "hsp70 and hsp40 to", "and hsp40 to hsp90", "hsp40 to hsp90 cycle", "to hsp90 cycle via", "hsp90 cycle via stip1", "via stip1 hop", "hop and", "and its tpr domains", "domains hern\u00e1ndez", "hern\u00e1ndez mp et al.", "mp et al. 2002a", "et al. 2002a b", "2002a b echeverriapc", "b echeverriapc &", "echeverriapc & picard d", "d 2010 li", "2010 li j", "li j et al.", "j et al. 2011", "et al. 2011 .", "al. 2011 . the", "2011 . the atp", ". the atp bound", "the atp bound form", "atp bound form of", "bound form of hsp90", "form of hsp90 leads", "of hsp90 leads to", "hsp90 leads to the", "leads to the displacement", "to the displacement of", "the displacement of stip1", "displacement of stip1 by", "of stip1 by immunophilins", "stip1 by immunophilins fkbp5", "by immunophilins fkbp5 or", "immunophilins fkbp5 or fkbp4", "fkbp5 or fkbp4 resulting", "or fkbp4 resulting in", "fkbp4 resulting in conformational", "resulting in conformational changes", "in conformational changes that", "conformational changes that allow", "changes that allow efficient", "that allow efficient hormone", "allow efficient hormone binding", "hormone binding li", "binding li j", "al. 2011 . ptges3", ". ptges3 p23", "p23 binds to", "binds to hsp90 complex", "to hsp90 complex finally", "hsp90 complex finally stabilizing", "complex finally stabilizing it", "finally stabilizing it in", "stabilizing it in the", "it in the conformation", "in the conformation with", "the conformation with a", "conformation with a high", "with a high hormone", "a high hormone binding", "high hormone binding affinity.", "hormone binding affinity. after", "binding affinity. after hydrolysis", "affinity. after hydrolysis of", "after hydrolysis of atp", "hydrolysis of atp the", "of atp the hormone", "atp the hormone bound", "the hormone bound shr", "hormone bound shr is", "bound shr is released", "shr is released from", "is released from hsp90", "released from hsp90 complex.", "from hsp90 complex. the", "hsp90 complex. the cytosolic", "complex. the cytosolic hormone", "the cytosolic hormone bound", "cytosolic hormone bound shr", "hormone bound shr can", "bound shr can be", "shr can be transported", "can be transported to", "be transported to the", "transported to the nucleus", "to the nucleus by", "the nucleus by several", "nucleus by several import", "by several import pathways", "several import pathways such", "import pathways such as", "pathways such as the", "such as the dynein", "as the dynein based", "the dynein based nuclear", "dynein based nuclear transport", "based nuclear transport along", "nuclear transport along microtubules", "transport along microtubules involving", "along microtubules involving the", "microtubules involving the transport", "involving the transport of", "the transport of the", "transport of the entire", "of the entire hsp90", "the entire hsp90 complex", "entire hsp90 complex or", "hsp90 complex or nuclear", "complex or nuclear localization", "or nuclear localization signals", "localization signals nls", "nls mediated nuclear", "mediated nuclear targeting by", "nuclear targeting by importins", "by importins tyagi", "importins tyagi rk", "al. 2006 . it", "2006 . it is", ". it is worth", "it is worth noting", "is worth noting that", "worth noting that gr", "noting that gr importin", "that gr importin interactions", "gr importin interactions can", "importin interactions can be", "interactions can be ligand", "can be ligand dependent", "be ligand dependent or", "ligand dependent or independent", "or independent freedman", "independent freedman &", "freedman & yamamoto 2004", "yamamoto 2004 picard", "2004 picard &", "picard & yamamoto 1987", "& yamamoto 1987 .", "yamamoto 1987 . in", "1987 . in the", ". in the nucleus", "in the nucleus ligand", "the nucleus ligand activated", "nucleus ligand activated shr", "ligand activated shr dimerizes", "shr dimerizes binds", "dimerizes binds specific", "binds specific sequences in", "specific sequences in the", "sequences in the dna", "the dna called", "dna called hormone", "called hormone responsive elements", "responsive elements hre", "hre and", "and recruits a number", "recruits a number of", "a number of coregulators", "number of coregulators that", "of coregulators that facilitate", "coregulators that facilitate gene", "that facilitate gene transcription.", "facilitate gene transcription. nuclear", "gene transcription. nuclear localization", "transcription. nuclear localization is", "nuclear localization is essential", "localization is essential for", "is essential for shrs", "essential for shrs to", "for shrs to transactivate", "shrs to transactivate their", "to transactivate their target", "transactivate their target genes", "target genes but", "genes but the", "but the same receptors", "the same receptors also", "same receptors also possess", "receptors also possess non", "also possess non genomic", "possess non genomic functions", "non genomic functions in", "genomic functions in the", "functions in the cytoplasm.

the", "in the cytoplasm.

the reactome", "the cytoplasm.

the reactome module", "cytoplasm.

the reactome module describes", "reactome module describes the", "module describes the atpase", "describes the atpase driven", "the atpase driven conformational", "atpase driven conformational cycle", "driven conformational cycle of", "conformational cycle of hsp90", "cycle of hsp90 that", "of hsp90 that regulates", "hsp90 that regulates ligand", "that regulates ligand dependent", "regulates ligand dependent activation", "ligand dependent activation of", "dependent activation of shrs.", "receptors shr are", "shr are transcription factors", "are transcription factors that become", "transcription factors that become activated", "factors that become activated upon", "that become activated upon sensing", "become activated upon sensing steroid", "activated upon sensing steroid hormones", "upon sensing steroid hormones such", "sensing steroid hormones such as", "steroid hormones such as glucocorticoids", "such as glucocorticoids mineralocorticoids", "glucocorticoids mineralocorticoids progesterone", "mineralocorticoids progesterone androgens", "progesterone androgens or", "or estrogen escriva et", "estrogen escriva et al", "et al 2000 griekspoor", "al 2000 griekspoor a", "2000 griekspoor a et", "griekspoor a et al. 2007", "et al. 2007 eick", "al. 2007 eick gn", "2007 eick gn &", "eick gn & thornton jw.", "gn & thornton jw. 2011", "& thornton jw. 2011 .", "thornton jw. 2011 . depending", "jw. 2011 . depending on", "2011 . depending on shr", ". depending on shr type", "depending on shr type and", "on shr type and the", "shr type and the presence", "type and the presence of", "and the presence of ligand", "presence of ligand they", "of ligand they show", "ligand they show different", "they show different subcellular localizations.", "show different subcellular localizations. whereas", "different subcellular localizations. whereas both", "subcellular localizations. whereas both unliganded", "localizations. whereas both unliganded and", "whereas both unliganded and liganded", "both unliganded and liganded estrogen", "unliganded and liganded estrogen receptors", "liganded estrogen receptors eralpha", "estrogen receptors eralpha and", "receptors eralpha and erbeta", "eralpha and erbeta are", "and erbeta are predominantly", "erbeta are predominantly nuclear", "are predominantly nuclear unliganded", "predominantly nuclear unliganded glucocorticoid", "glucocorticoid gr and", "gr and androgen receptors", "and androgen receptors ar", "receptors ar are", "ar are mostly located", "are mostly located in the", "mostly located in the cytoplasm", "located in the cytoplasm and", "in the cytoplasm and completely", "the cytoplasm and completely translocate", "cytoplasm and completely translocate to", "and completely translocate to the", "completely translocate to the nucleus", "translocate to the nucleus only", "to the nucleus only after", "the nucleus only after binding", "nucleus only after binding hormone", "after binding hormone htun", "binding hormone htun h", "hormone htun h et", "htun h et al. 1999", "et al. 1999 stenoien", "al. 1999 stenoien d", "1999 stenoien d et", "stenoien d et al. 2000", "et al. 2000 tyagi", "al. 2000 tyagi rk", "2000 tyagi rk et", "tyagi rk et al. 2000", "et al. 2000 cadepond", "al. 2000 cadepond f", "2000 cadepond f et", "cadepond f et al. 1992", "et al. 1992 jewell", "al. 1992 jewell cm", "1992 jewell cm et", "jewell cm et al. 1995", "et al. 1995 kumar", "al. 1995 kumar s", "1995 kumar s et", "kumar s et al. 2006", "s et al. 2006 .", "et al. 2006 . the", "al. 2006 . the unliganded", "2006 . the unliganded mineralocorticoid", ". the unliganded mineralocorticoid receptor", "unliganded mineralocorticoid receptor mr", "receptor mr is", "mr is partially cytoplasmic", "is partially cytoplasmic but can", "partially cytoplasmic but can be", "cytoplasmic but can be found", "but can be found in", "can be found in nucleus", "be found in nucleus in", "found in nucleus in the", "in nucleus in the ligand", "nucleus in the ligand bound", "in the ligand bound or", "the ligand bound or ligand", "ligand bound or ligand free", "bound or ligand free form", "ligand free form nishi", "free form nishi m", "form nishi m &", "nishi m & kawata m", "m & kawata m 2007", "& kawata m 2007 .", "kawata m 2007 . the", "m 2007 . the progesterone", "2007 . the progesterone receptor", "the progesterone receptor pr", "receptor pr exists", "pr exists in two", "in two forms pra", "two forms pra and", "forms pra and prb", "pra and prb with", "and prb with different", "prb with different ratios", "with different ratios of nuclear", "different ratios of nuclear versus", "ratios of nuclear versus cytoplasmic", "of nuclear versus cytoplasmic localization", "nuclear versus cytoplasmic localization of", "versus cytoplasmic localization of the", "cytoplasmic localization of the unliganded", "localization of the unliganded receptor.", "of the unliganded receptor. in", "the unliganded receptor. in most", "unliganded receptor. in most cell", "receptor. in most cell contexts", "most cell contexts the", "cell contexts the pra", "contexts the pra isoform", "the pra isoform is a", "pra isoform is a repressor", "isoform is a repressor of", "is a repressor of the", "a repressor of the shorter", "repressor of the shorter prb", "of the shorter prb isoform", "shorter prb isoform and", "prb isoform and without", "isoform and without hormone", "and without hormone induction it", "without hormone induction it is", "hormone induction it is mostly", "induction it is mostly located", "it is mostly located in", "is mostly located in the", "mostly located in the nucleus", "in the nucleus whereas", "the nucleus whereas prb", "nucleus whereas prb distributes", "whereas prb distributes both in", "prb distributes both in the", "distributes both in the nucleus", "both in the nucleus and", "in the nucleus and in", "the nucleus and in the", "nucleus and in the cytoplasm", "in the cytoplasm lim", "the cytoplasm lim cs", "cytoplasm lim cs et", "lim cs et al. 1999", "et al. 1999 griekspoor", "al. 1999 griekspoor a", "1999 griekspoor a et", "a et al. 2007 .", "et al. 2007 . in", "al. 2007 . in the", "2007 . in the absence", ". in the absence of", "in the absence of ligand", "absence of ligand members", "of ligand members of", "ligand members of the", "members of the steroid receptor", "of the steroid receptor family", "the steroid receptor family remain", "steroid receptor family remain sequestered", "receptor family remain sequestered in", "family remain sequestered in the", "remain sequestered in the cytoplasm", "sequestered in the cytoplasm and/or", "in the cytoplasm and/or nucleus", "the cytoplasm and/or nucleus in", "cytoplasm and/or nucleus in the", "and/or nucleus in the complex", "nucleus in the complex with", "in the complex with proteins", "the complex with proteins of", "complex with proteins of hsp70/hsp90", "with proteins of hsp70/hsp90 chaperone", "proteins of hsp70/hsp90 chaperone machinery", "hsp70/hsp90 chaperone machinery pratt", "chaperone machinery pratt wb", "machinery pratt wb &", "pratt wb & dittmar kd1998", "wb & dittmar kd1998 .", "& dittmar kd1998 . the", "dittmar kd1998 . the highly", "kd1998 . the highly dynamic", ". the highly dynamic atp", "the highly dynamic atp dependent", "highly dynamic atp dependent interactions", "dynamic atp dependent interactions of", "atp dependent interactions of shrs", "dependent interactions of shrs with", "interactions of shrs with hsp90", "of shrs with hsp90 complexes", "shrs with hsp90 complexes regulate", "with hsp90 complexes regulate shr", "hsp90 complexes regulate shr cellular", "complexes regulate shr cellular location", "shr cellular location protein", "cellular location protein stability", "protein stability competency to", "stability competency to bind", "competency to bind steroid hormones", "to bind steroid hormones and", "bind steroid hormones and transcriptional", "steroid hormones and transcriptional activity", "and transcriptional activity echeverria", "transcriptional activity echeverria pc", "activity echeverria pc &", "echeverria pc & picard d", "pc & picard d 2010", "& picard d 2010 .", "picard d 2010 . understanding", "d 2010 . understanding the", "2010 . understanding the mechanism", ". understanding the mechanism of", "understanding the mechanism of atpase", "the mechanism of atpase activity", "mechanism of atpase activity of", "of atpase activity of hsp90", "atpase activity of hsp90 is", "activity of hsp90 is mostly", "of hsp90 is mostly based", "hsp90 is mostly based on", "is mostly based on structural", "mostly based on structural and", "based on structural and functional", "on structural and functional studies", "structural and functional studies of", "and functional studies of the", "functional studies of the saccharomyces", "studies of the saccharomyces cerevisiae", "of the saccharomyces cerevisiae hsp90", "the saccharomyces cerevisiae hsp90 complexes", "cerevisiae hsp90 complexes meyer", "hsp90 complexes meyer p", "complexes meyer p et", "meyer p et al. 2003", "et al. 2003 2004", "2003 2004 ali", "2004 ali mm et", "ali mm et al. 2006", "et al. 2006 prodromou", "al. 2006 prodromou c", "2006 prodromou c et", "prodromou c et al. 2000", "et al. 2000 prodromou", "al. 2000 prodromou c", "2000 prodromou c 2012", "prodromou c 2012 . the", "c 2012 . the atpase", "2012 . the atpase cycle", ". the atpase cycle of", "the atpase cycle of human", "atpase cycle of human hsp90", "cycle of human hsp90 is", "of human hsp90 is less", "human hsp90 is less well", "hsp90 is less well understood", "less well understood however", "well understood however several", "understood however several studies", "however several studies suggest that", "several studies suggest that the", "studies suggest that the underlying", "suggest that the underlying enzymatic", "that the underlying enzymatic mechanisms", "the underlying enzymatic mechanisms and", "underlying enzymatic mechanisms and a", "enzymatic mechanisms and a set", "mechanisms and a set of", "and a set of conformational", "a set of conformational changes", "set of conformational changes that", "of conformational changes that accompany", "conformational changes that accompany the", "changes that accompany the atpase", "that accompany the atpase cycle", "accompany the atpase cycle are", "the atpase cycle are highly", "atpase cycle are highly similar", "cycle are highly similar in", "are highly similar in both", "highly similar in both species", "in both species richter", "both species richter k", "species richter k et", "richter k et al. 2008", "et al. 2008 vaughan", "al. 2008 vaughan ck", "2008 vaughan ck et", "vaughan ck et al. 2009", "ck et al. 2009 .", "et al. 2009 . nascent", "al. 2009 . nascent shr", "2009 . nascent shr proteins", ". nascent shr proteins are", "nascent shr proteins are chaperoned", "shr proteins are chaperoned by", "proteins are chaperoned by hsp70", "are chaperoned by hsp70 and", "chaperoned by hsp70 and hsp40", "by hsp70 and hsp40 to", "hsp70 and hsp40 to hsp90", "and hsp40 to hsp90 cycle", "hsp40 to hsp90 cycle via", "to hsp90 cycle via stip1", "cycle via stip1 hop", "hop and its", "tpr domains hern\u00e1ndez", "domains hern\u00e1ndez mp", "hern\u00e1ndez mp et al. 2002a", "mp et al. 2002a b", "al. 2002a b echeverriapc", "2002a b echeverriapc &", "b echeverriapc & picard", "echeverriapc & picard d 2010", "picard d 2010 li", "d 2010 li j", "2010 li j et", "li j et al. 2011", "j et al. 2011 .", "et al. 2011 . the", "al. 2011 . the atp", "2011 . the atp bound", ". the atp bound form", "the atp bound form of", "atp bound form of hsp90", "bound form of hsp90 leads", "form of hsp90 leads to", "of hsp90 leads to the", "hsp90 leads to the displacement", "leads to the displacement of", "to the displacement of stip1", "the displacement of stip1 by", "displacement of stip1 by immunophilins", "of stip1 by immunophilins fkbp5", "stip1 by immunophilins fkbp5 or", "by immunophilins fkbp5 or fkbp4", "immunophilins fkbp5 or fkbp4 resulting", "fkbp5 or fkbp4 resulting in", "or fkbp4 resulting in conformational", "fkbp4 resulting in conformational changes", "resulting in conformational changes that", "in conformational changes that allow", "conformational changes that allow efficient", "changes that allow efficient hormone", "that allow efficient hormone binding", "efficient hormone binding li", "hormone binding li j", "binding li j et", "et al. 2011 . ptges3", "2011 . ptges3 p23", "ptges3 p23 binds", "p23 binds to hsp90", "binds to hsp90 complex finally", "to hsp90 complex finally stabilizing", "hsp90 complex finally stabilizing it", "complex finally stabilizing it in", "finally stabilizing it in the", "stabilizing it in the conformation", "it in the conformation with", "in the conformation with a", "the conformation with a high", "conformation with a high hormone", "with a high hormone binding", "a high hormone binding affinity.", "high hormone binding affinity. after", "hormone binding affinity. after hydrolysis", "binding affinity. after hydrolysis of", "affinity. after hydrolysis of atp", "after hydrolysis of atp the", "hydrolysis of atp the hormone", "of atp the hormone bound", "atp the hormone bound shr", "the hormone bound shr is", "hormone bound shr is released", "bound shr is released from", "shr is released from hsp90", "is released from hsp90 complex.", "released from hsp90 complex. the", "from hsp90 complex. the cytosolic", "hsp90 complex. the cytosolic hormone", "complex. the cytosolic hormone bound", "the cytosolic hormone bound shr", "cytosolic hormone bound shr can", "hormone bound shr can be", "bound shr can be transported", "shr can be transported to", "can be transported to the", "be transported to the nucleus", "transported to the nucleus by", "to the nucleus by several", "the nucleus by several import", "nucleus by several import pathways", "by several import pathways such", "several import pathways such as", "import pathways such as the", "pathways such as the dynein", "such as the dynein based", "as the dynein based nuclear", "the dynein based nuclear transport", "dynein based nuclear transport along", "based nuclear transport along microtubules", "nuclear transport along microtubules involving", "transport along microtubules involving the", "along microtubules involving the transport", "microtubules involving the transport of", "involving the transport of the", "the transport of the entire", "transport of the entire hsp90", "of the entire hsp90 complex", "the entire hsp90 complex or", "entire hsp90 complex or nuclear", "hsp90 complex or nuclear localization", "complex or nuclear localization signals", "nuclear localization signals nls", "signals nls mediated", "nls mediated nuclear targeting", "mediated nuclear targeting by importins", "targeting by importins tyagi", "by importins tyagi rk", "importins tyagi rk et", "et al. 2006 . it", "al. 2006 . it is", "2006 . it is worth", ". it is worth noting", "it is worth noting that", "is worth noting that gr", "worth noting that gr importin", "noting that gr importin interactions", "that gr importin interactions can", "gr importin interactions can be", "importin interactions can be ligand", "interactions can be ligand dependent", "can be ligand dependent or", "be ligand dependent or independent", "dependent or independent freedman", "or independent freedman &", "independent freedman & yamamoto", "& yamamoto 2004 picard", "yamamoto 2004 picard &", "2004 picard & yamamoto", "picard & yamamoto 1987 .", "& yamamoto 1987 . in", "yamamoto 1987 . in the", "1987 . in the nucleus", ". in the nucleus ligand", "in the nucleus ligand activated", "the nucleus ligand activated shr", "nucleus ligand activated shr dimerizes", "activated shr dimerizes binds", "shr dimerizes binds specific", "dimerizes binds specific sequences", "binds specific sequences in the", "specific sequences in the dna", "in the dna called", "the dna called hormone", "dna called hormone responsive", "hormone responsive elements hre", "hre and recruits", "and recruits a number of", "recruits a number of coregulators", "a number of coregulators that", "number of coregulators that facilitate", "of coregulators that facilitate gene", "coregulators that facilitate gene transcription.", "that facilitate gene transcription. nuclear", "facilitate gene transcription. nuclear localization", "gene transcription. nuclear localization is", "transcription. nuclear localization is essential", "nuclear localization is essential for", "localization is essential for shrs", "is essential for shrs to", "essential for shrs to transactivate", "for shrs to transactivate their", "shrs to transactivate their target", "to transactivate their target genes", "their target genes but", "target genes but the", "genes but the same", "but the same receptors also", "the same receptors also possess", "same receptors also possess non", "receptors also possess non genomic", "also possess non genomic functions", "possess non genomic functions in", "non genomic functions in the", "genomic functions in the cytoplasm.

the", "functions in the cytoplasm.

the reactome", "in the cytoplasm.

the reactome module", "the cytoplasm.

the reactome module describes", "cytoplasm.

the reactome module describes the", "reactome module describes the atpase", "module describes the atpase driven", "describes the atpase driven conformational", "the atpase driven conformational cycle", "atpase driven conformational cycle of", "driven conformational cycle of hsp90", "conformational cycle of hsp90 that", "cycle of hsp90 that regulates", "of hsp90 that regulates ligand", "hsp90 that regulates ligand dependent", "that regulates ligand dependent activation", "regulates ligand dependent activation of", "ligand dependent activation of shrs." ] }, { "record_id": "GLY_000594_1_276", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "349425", "r hsa", "hsa 349425", "r hsa 349425" ] }, { "record_id": "GLY_000594_1_276", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "autodegradation of", "of the", "the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase cop1", "autodegradation of the", "of the 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"in abrogation of", "abrogation of the", "of the ubiquitination", "the ubiquitination and", "ubiquitination and degradation", "and degradation of", "degradation of p53", "p53 dornan", "dornan et al.", "al. 2006", "cop1 is one of", "is one of several", "of several e3", "several e3 ubiquitin", "e3 ubiquitin ligases responsible", "ubiquitin ligases responsible for", "ligases responsible for the", "responsible for the tight", "for the tight regulation", "the tight regulation of", "regulation of p53", "of p53 abundance.", "p53 abundance. following", "abundance. following dna", "dna damage cop1", "damage cop1 dissociates", "cop1 dissociates from p53", "dissociates from p53 and", "p53 and is", "and is inactivated", "is inactivated by autodegradation", "inactivated by autodegradation via", "by autodegradation via a", "autodegradation via a pathway", "via a pathway involving", "a pathway involving atm", "pathway involving atm phosphorylation", "involving atm phosphorylation of", 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notch", "notch signaling", "signaling was", "was first", "first identified", "identified in", "in drosophila", "where it", "it has", "has been", "been studied", "studied in", "in detail", "detail at", "at the", "the genetic", "biochemical and", "and cellular", "cellular levels", "reviewed in", "in justice", "2006 .", "signaling to", "to the", "the nucleus", "nucleus is", "is thought", "thought always", "always to", "to be", "be mediated", "mediated by", "by one", "one specific", "specific dna", "dna binding", "binding transcription", "transcription factor", "suppressor of", "of hairless.", "in mammals", "the homologous", "homologous genes", "genes are", "are called", "called cbf1", "or rbpjkappa", "while in", "in worms", "worms they", "they are", "called lag", "lag 1", "so that", "that the", "the acronym", "acronym \\csl\\", "\\csl\\ has", "been given", "given to", "to this", "this conserved", "conserved transcription", "factor family.", "there are", "are at", "at least", "least two", "two human", "human csl", "csl homologues", "which are", "are now", "now named", "named rbpj", "rbpj and", "and rbpjl.

csl", "rbpjl.

csl is", "is an", "an example", "example of", "of a", "a bifunctional", "bifunctional dna", "factor that", "that mediates", "mediates repression", "repression of", "of specific", "specific target", "target genes", "genes in", "in one", "one context", "but activation", "activation of", "of the", "the same", "same targets", "targets in", "in another", "another context.", "this bifunctionality", "bifunctionality is", "is mediated", "by the", "the association", "association of", "specific co", "co repressor", "repressor complexes", "complexes vs.", "vs. specific", "co activator", "activator complexes", "complexes in", "in different", "different contexts", "namely in", "in the", "the absence", "absence or", "or presence", "presence of", "of notch", "notch signaling.

in", "signaling.

in drosophila", "su h", "represses target", "target gene", "gene transcription", "transcription in", "absence of", "but activates", "activates target", "genes during", "during notch", "notch signaling.", "least some", "some of", "the mammalian", "mammalian csl", "homologues are", "are believed", "believed also", "also to", "be bifunctional", "and to", "to mediate", "mediate target", "gene repression", "repression in", "and activation", "activation in", "the presence", "notch signaling.

notch", "signaling.

notch co", "activator and", "and co", "repressor complexes:", "complexes: this", "this repression", "repression is", "by at", "least one", "co r", "bound to", "to csl", "csl in", "this co", "repressor complex", "complex consists", "consists of", "of at", "least three", "three distinct", "distinct co", "repressor proteins:", "proteins: hairless", "and dctbp", "drosophila c", "c terminal", "terminal binding", "binding protein", "protein .", "hairless has", "been show", "show to", "to bind", "bind directly", "directly to", "to su", "and groucho", "groucho and", "dctbp have", "have been", "been shown", "shown to", "to hairless", "2002 .", "all three", "three of", "the co", "repressor proteins", "proteins have", "be necessary", "necessary for", "for proper", "proper gene", "gene regulation", "regulation during", "signaling in", "in vivo", "2005 .

in", ".

in mammals", "same general", "general pathway", "pathway and", "and mechanisms", "mechanisms are", "are observed", "where csl", "csl proteins", "proteins are", "are bifunctional", "transcription factors", "that bind", "bind to", "to co", "complexes to", "mediate repression", "and bind", "mediate activation", "there may", "may be", "be multiple", "multiple co", "rather than", "than the", "the single", "single hairless", "hairless co", "complex that", "that has", "been observed", "observed in", "in drosophila.", "

during notch", "in all", "all systems", "the notch", "notch transmembrane", "transmembrane receptor", "receptor is", "is cleaved", "cleaved and", "and the", "notch intracellular", "intracellular domain", "translocates to", "it there", "there functions", "functions as", "as a", "a specific", "specific transcription", "transcription co", "activator for", "for csl", "csl proteins.", "nicd replaces", "replaces the", "r complex", "complex bound", "thus resulting", "resulting in", "in de", "de repression", "notch target", "the nucleus.", "once bound", "nicd and", "and csl", "proteins recruit", "recruit an", "an additional", "additional co", "activator protein", "to form", "form a", "a csl", "csl nicd", "nicd mam", "mam ternary", "ternary co", "co a", "a complex", "complex was", "was initially", "initially thought", "thought to", "be sufficient", "sufficient to", "some notch", "target genes.", "there now", "now is", "is evidence", "evidence that", "that still", "still other", "other co", "co activators", "activators and", "and additional", "additional dna", "factors are", "are required", "required in", "in at", "some contexts", "in barolo", "2002 .

mammalian", ".

mammalian csl", "csl corepressor", "corepressor complexes:", "complexes: in", "of activated", "activated notch", "dna bound", "bound csl", "recruit a", "a corepressor", "corepressor complex", "complex to", "to maintain", "maintain target", "the repressed", "repressed state", "state until", "until notch", "notch is", "is specifically", "specifically activated.", "activated. the", "mammalian corepressor", "corepressor complexes", "complexes include", "include ncor", "ncor complexes", "but may", "may also", "also include", "include additional", "additional corepressor", "corepressor proteins", "such as", "as sharp", "in mumm", "2000 and", "and kovall", "2007 .", ". the", "the exact", "exact composition", "composition of", "the csl", "csl ncor", "ncor complex", "complex is", "is not", "not known", "but in", "in other", "other pathways", "pathways the", "the \\core\\", "\\core\\ ncor", "ncor corepressor", "complex includes", "includes at", "one ncor", "ncor protein", "one histone", "histone deacetylase", "deacetylase protein", "and one", "one tbl1", "tbl1 protein", "in rosenfeld", ". in", "in some", "the core", "core ncor", "complex may", "also recruit", "recruit additional", "proteins or", "or complexes", "as the", "the sin3", "sin3 complex", "which consists", "of sin3", "and sap30", "or other", "other sin3", "sin3 associated", "associated proteins.", "proteins. an", "additional csl", "ncor binding", "binding corepressor", "also contribute", "contribute to", "complex in", "complex also", "also includes", "includes a", "bifunctional cofactor", "that is", "is present", "present in", "in both", "both csl", "complexes and", "csl coactivator", "coactivator complexes", "and may", "may function", "function in", "the binding", "binding of", "of nicd", "and displacement", "displacement of", "the corepressor", "complex during", "during activated", "2000 .

mammalian", "coactivator complexes:", "complexes: upon", "upon activation", "cleavage of", "the transmembrane", "transmembrane notch", "notch receptor", "receptor releases", "releases the", "which translocates", "it binds", "binds to", "csl and", "and displaces", "displaces the", "complex from", "from csl", "the resulting", "resulting csl", "nicd \\binary", "\\binary complex\\", "complex\\ then", "then recruits", "recruits an", "additional coactivator", "a ternary", "ternary complex.", "complex. the", "the ternary", "ternary complex", "complex then", "recruits additional", "more general", "general coactivators", "as creb", "creb binding", "or the", "the related", "related p300", "p300 coactivator", "and a", "a number", "number of", "of histone", "histone acetytransferase", "including gcn5", "gcn5 and", "and pcaf", ". there", "there is", "that mam", "mam also", "also can", "can subsequently", "subsequently recruit", "recruit specific", "specific kinases", "kinases that", "that phosphorylate", "phosphorylate nicd", "to downregulate", "downregulate its", "its function", "function and", "and turn", "turn off", "off notch", "2004 .

combinatorial", ".

combinatorial complexity", "complexity in", "in transcription", "transcription cofactor", "cofactor complexes:", "complexes: hdac9", "hdac9 has", "has at", "least 7", "7 splice", "splice isoforms", "with some", "some having", "having distinct", "distinct interaction", "interaction and", "and functional", "functional properties.", "properties. isoforms", "isoforms 6", "6 and", "and 7", "7 interact", "interact with", "with ncor1.", "ncor1. isoforms", "isoforms 1", "1 and", "and 4", "4 interact", "with mef2", "which is", "is a", "binding cofactor", "cofactor for", "for a", "a subset", "subset of", "of hlh", "hlh proteins.", "proteins. isoform", "isoform 3", "3 interacts", "interacts with", "with both", "both ncor1", "ncor1 and", "and mef2.", "mef2. although", "although many", "many hdacs", "hdacs only", "only have", "have one", "one or", "or two", "two isoforms", "this complexity", "complexity for", "for hdac9", "hdac9 illustrates", "illustrates the", "the level", "level of", "of transcript", "transcript complexity", "complexity and", "functional specificity", "specificity that", "that such", "such \\general\\", "\\general\\ transcriptional", "transcriptional cofactors", "cofactors can", "can have.", "the notch hlh", "hlh transcription pathway:", "pathway:

", "

notch signaling", "notch signaling was", "signaling was first", "was first identified", "first identified in", "identified in drosophila", "drosophila where", "where it has", "it has been", "has been studied", "been studied in", "studied in detail", "in detail at", "detail at the", "at the genetic", "genetic molecular", "molecular biochemical", "biochemical and cellular", "and cellular levels", "levels reviewed", "reviewed in justice", "justice 2002", "2002 bray", "bray 2006", "2006 schweisguth", "schweisguth 2004", "2004 louvri", "louvri 2006", "drosophila notch", "notch signaling to", "signaling to the", "to the nucleus", "the nucleus is", "nucleus is thought", "is thought always", "thought always to", "always to be", "to be mediated", "be mediated by", "mediated by one", "by one specific", "one specific dna", "specific dna binding", "dna binding transcription", "binding transcription factor", "factor suppressor", "suppressor of hairless.", "hairless. in", "mammals the", "the homologous genes", "homologous genes are", "genes are called", "are called cbf1", "cbf1 or", "while in worms", "in worms they", "worms they are", "they are called", "are called lag", "called lag 1", "1 so", "so that the", "that the acronym", "the acronym \\csl\\", "acronym \\csl\\ has", "\\csl\\ has been", "has been given", "been given to", "given to this", "to this conserved", "this conserved transcription", "conserved transcription factor", "transcription factor family.", "family. there", "there are at", "are at least", "at least two", "least two human", "two human csl", "human csl homologues", "homologues which", "which are now", "are now named", "now named rbpj", "named rbpj and", "rbpj and rbpjl.

csl", "and rbpjl.

csl is", "rbpjl.

csl is an", "is an example", "an example of", "example of a", "of a bifunctional", "a bifunctional dna", "bifunctional dna binding", "transcription factor that", "factor that mediates", "that mediates repression", "mediates repression of", "repression of specific", "of specific target", "specific target genes", "target genes in", "genes in one", "in one context", "context but", "but activation of", "activation of the", "of the same", "the same targets", "same targets in", "targets in another", "in another context.", "context. this", "this bifunctionality is", "bifunctionality is mediated", "is mediated by", "mediated by the", "by the association", "the association of", "association of specific", "of specific co", "specific co repressor", "co repressor complexes", "repressor complexes vs.", "complexes vs. specific", "vs. specific co", "specific co activator", "co activator complexes", "activator complexes in", "complexes in different", "in different contexts", "contexts namely", "namely in the", "in the absence", "the absence or", "absence or presence", "or presence of", "presence of notch", "of notch signaling.

in", "notch signaling.

in drosophila", "drosophila su", "h represses", "represses target gene", "target gene transcription", "gene transcription in", "transcription in the", "the absence of", "absence of notch", "of notch signaling", "signaling but", "but activates target", "activates target genes", "target genes during", "genes during notch", "during notch signaling.", "signaling. at", "at least some", "least some of", "some of the", "of the mammalian", "the mammalian csl", "mammalian csl homologues", "csl homologues are", "homologues are believed", "are believed also", "believed also to", "also to be", "to be bifunctional", "bifunctional and", "and to mediate", "to mediate target", "mediate target gene", "target gene repression", "gene repression in", "repression in the", "signaling and", "and activation in", "activation in the", "in the presence", "the presence of", "of notch signaling.

notch", "notch signaling.

notch co", "signaling.

notch co activator", "co activator and", "activator and co", "and co repressor", "co repressor complexes:", "repressor complexes: this", "complexes: this repression", "this repression is", "repression is mediated", "mediated by at", "by at least", "at least one", "least one specific", "one specific co", "complexes co", "r bound", "bound to csl", "to csl in", "csl in the", "of notch signaling.", "signaling. in", "drosophila this", "this co repressor", "co repressor complex", "repressor complex consists", "complex consists of", "consists of at", "of at least", "at least three", "least three distinct", "three distinct co", "distinct co repressor", "co repressor proteins:", "repressor proteins: hairless", "hairless groucho", "dctbp drosophila", "drosophila c terminal", "c terminal binding", "terminal binding protein", "binding protein .", ". hairless", "hairless has been", "has been show", "been show to", "show to bind", "to bind directly", "bind directly to", "directly to su", "to su h", "and groucho and", "groucho and dctbp", "and dctbp have", "dctbp have been", "have been shown", "been shown to", "shown to bind", "directly to hairless", "hairless barolo", "barolo 2002", ". all", "all three of", "three of the", "of the co", "the co repressor", "co repressor proteins", "repressor proteins have", "proteins have been", "shown to be", "to be necessary", "be necessary for", "necessary for proper", "for proper gene", "proper gene regulation", "gene regulation during", "regulation during notch", "during notch signaling", "notch signaling in", "signaling in vivo", "vivo nagel", "nagel 2005", "2005 .

in mammals", "the same general", "same general pathway", "general pathway and", "pathway and mechanisms", "and mechanisms are", "mechanisms are observed", "observed where", "where csl proteins", "csl proteins are", "proteins are bifunctional", "are bifunctional dna", "binding transcription factors", "factors tfs", "that bind to", "bind to co", "to co repressor", "repressor complexes to", "complexes to mediate", "to mediate repression", "mediate repression in", "and bind to", "to co activator", "to mediate activation", "mediate activation in", "signaling. however", "however in", "mammals there", "there may be", "may be multiple", "be multiple co", "multiple co repressor", "complexes rather", "rather than the", "than the single", "the single hairless", "single hairless co", "hairless co repressor", "repressor complex that", "complex that has", "that has been", "has been observed", "been observed in", "observed in drosophila.", "drosophila.

during", "

during notch signaling", "signaling in all", "in all systems", "systems the", "the notch transmembrane", "notch transmembrane receptor", "transmembrane receptor is", "receptor is cleaved", "is cleaved and", "cleaved and the", "and the notch", "the notch intracellular", "notch intracellular domain", "domain nicd", "nicd translocates", "translocates to the", "nucleus where", "where it there", "it there functions", "there functions as", "functions as a", "as a specific", "a specific transcription", "specific transcription co", "transcription co activator", "co activator for", "activator for csl", "for csl proteins.", "proteins. in", "in the nucleus", "nucleus nicd", "nicd replaces the", "replaces the co", "the co r", "co r complex", "r complex bound", "complex bound to", "csl thus", "thus resulting in", "resulting in de", "in de repression", "de repression of", "notch target genes", "genes in the", "in the nucleus.", "nucleus. once", "once bound to", "nicd and csl", "and csl proteins", "csl proteins recruit", "proteins recruit an", "recruit an additional", "an additional co", "additional co activator", "co activator protein", "protein mastermind", "mastermind to", "to form a", "form a csl", "a csl nicd", "csl nicd mam", "nicd mam ternary", "mam ternary co", "ternary co activator", "activator co", "a complex.", "complex. this", "this co a", "co a complex", "a complex was", "complex was initially", "was initially thought", "initially thought to", "thought to be", "to be sufficient", "be sufficient to", "sufficient to mediate", "mediate activation of", "least some notch", "some notch target", "notch target genes.", "genes. however", "however there", "there now is", "now is evidence", "is evidence that", "evidence that still", "that still other", "still other co", "other co activators", "co activators and", "activators and additional", "and additional dna", "additional dna binding", "transcription factors are", "factors are required", "are required in", "required in at", "in at least", "least some contexts", "contexts reviewed", "reviewed in barolo", "2002 .

mammalian csl", ".

mammalian csl corepressor", "csl corepressor complexes:", "corepressor complexes: in", "complexes: in the", "absence of activated", "of activated notch", "activated notch signaling", "signaling dna", "dna bound csl", "bound csl proteins", "proteins recruit a", "recruit a corepressor", "a corepressor complex", "corepressor complex to", "complex to maintain", "to maintain target", "maintain target genes", "in the repressed", "the repressed state", "repressed state until", "state until notch", "until notch is", "notch is specifically", "is specifically activated.", "specifically activated. the", "activated. the mammalian", "the mammalian corepressor", "mammalian corepressor complexes", "corepressor complexes include", "complexes include ncor", "include ncor complexes", "complexes but", "but may also", "may also include", "also include additional", "include additional corepressor", "additional corepressor proteins", "proteins such", "such as sharp", "sharp reviewed", "reviewed in mumm", "mumm 2000", "2000 and kovall", "kovall 2007", "2007 . the", ". the exact", "the exact composition", "exact composition of", "composition of the", "of the csl", "the csl ncor", "csl ncor complex", "ncor complex is", "complex is not", "is not known", "known but", "but in other", "in other pathways", "other pathways the", "pathways the \\core\\", "the \\core\\ ncor", "\\core\\ ncor corepressor", "ncor corepressor complex", "corepressor complex includes", "complex includes at", "includes at least", "least one ncor", "one ncor protein", "protein ncor1", "ncor1 ncor2", "ncor2 cir", "one histone deacetylase", "histone deacetylase protein", "protein hdac1", "hdac1 hdac2", "hdac2 hdac3", "hdac3 etc", "and one tbl1", "one tbl1 protein", "protein tbl1x", "tbl1x tbl1xr1", "reviewed in rosenfeld", "rosenfeld 2006", "2006 . in", ". in some", "in some contexts", "contexts the", "the core ncor", "core ncor corepressor", "corepressor complex may", "complex may also", "may also recruit", "also recruit additional", "recruit additional corepressor", "corepressor proteins or", "proteins or complexes", "complexes such", "such as the", "as the sin3", "the sin3 complex", "complex which", "which consists of", "consists of sin3", "sin3 sin3a", "sin3a sin3b", "sap30 or", "or other sin3", "other sin3 associated", "sin3 associated proteins.", "associated proteins. an", "proteins. an additional", "an additional csl", "ncor binding corepressor", "corepressor sharp", "sharp may", "may also contribute", "also contribute to", "contribute to the", "to the csl", "the csl corepressor", "csl corepressor complex", "corepressor complex in", "complex in some", "contexts oswald", "oswald 2002", "2002 . the", ". the csl", "corepressor complex also", "complex also includes", "also includes a", "includes a bifunctional", "a bifunctional cofactor", "cofactor skip", "skip that", "that is present", "is present in", "present in both", "in both csl", "both csl corepressor", "csl corepressor complexes", "corepressor complexes and", "complexes and csl", "and csl coactivator", "csl coactivator complexes", "and may function", "may function in", "function in the", "in the binding", "the binding of", "binding of nicd", "of nicd and", "nicd and displacement", "and displacement of", "displacement of the", "of the corepressor", "the corepressor complex", "corepressor complex during", "complex during activated", "during activated notch", "signaling zhou", "zhou 2000", "2000 .

mammalian csl", ".

mammalian csl coactivator", "csl coactivator complexes:", "coactivator complexes: upon", "complexes: upon activation", "upon activation of", "activation of notch", "signaling cleavage", "cleavage of the", "of the transmembrane", "the transmembrane notch", "transmembrane notch receptor", "notch receptor releases", "receptor releases the", "releases the notch", "which translocates to", "where it binds", "it binds to", "binds to csl", "to csl and", "csl and displaces", "and displaces the", "displaces the corepressor", "corepressor complex from", "complex from csl", "csl reviewed", ". the resulting", "the resulting csl", "resulting csl nicd", "csl nicd \\binary", "nicd \\binary complex\\", "\\binary complex\\ then", "complex\\ then recruits", "then recruits an", "recruits an additional", "an additional coactivator", "coactivator mastermind", "mastermind mam", "form a ternary", "a ternary complex.", "ternary complex. the", "complex. the ternary", "the ternary complex", "ternary complex then", "complex then recruits", "then recruits additional", "additional more", "more general coactivators", "coactivators such", "such as creb", "as creb binding", "creb binding protein", "protein cbp", "or the related", "the related p300", "related p300 coactivator", "coactivator and", "and a number", "a number of", "number of histone", "of histone acetytransferase", "acetytransferase hat", "hat proteins", "proteins including", "including gcn5 and", "gcn5 and pcaf", "pcaf fryer", "fryer 2002", "2002 . there", ". there is", "there is evidence", "evidence that mam", "that mam also", "mam also can", "also can subsequently", "can subsequently recruit", "subsequently recruit specific", "recruit specific kinases", "specific kinases that", "kinases that phosphorylate", "that phosphorylate nicd", "nicd to", "to downregulate its", "downregulate its function", "its function and", "function and turn", "and turn off", "turn off notch", "off notch signaling", "signaling fryer", "fryer 2004", "2004 .

combinatorial complexity", ".

combinatorial complexity in", "complexity in transcription", "in transcription cofactor", "transcription cofactor complexes:", "cofactor complexes: hdac9", "complexes: hdac9 has", "hdac9 has at", "has at least", "at least 7", "least 7 splice", "7 splice isoforms", "isoforms with", "with some having", "some having distinct", "having distinct interaction", "distinct interaction and", "interaction and functional", "and functional properties.", "functional properties. isoforms", "properties. isoforms 6", "isoforms 6 and", "6 and 7", "and 7 interact", "7 interact with", "interact with ncor1.", "with ncor1. isoforms", "ncor1. isoforms 1", "isoforms 1 and", "1 and 4", "and 4 interact", "4 interact with", "interact with mef2", "mef2 sparrow", "sparrow 1999", "which is a", "is a specific", "a specific dna", "dna binding cofactor", "binding cofactor for", "cofactor for a", "for a subset", "a subset of", "subset of hlh", "of hlh proteins.", "hlh proteins. isoform", "proteins. isoform 3", "isoform 3 interacts", "3 interacts with", "interacts with both", "with both ncor1", "both ncor1 and", "ncor1 and mef2.", "and mef2. although", "mef2. although many", "although many hdacs", "many hdacs only", "hdacs only have", "only have one", "have one or", "one or two", "or two isoforms", "isoforms this", "this complexity for", "complexity for hdac9", "for hdac9 illustrates", "hdac9 illustrates the", "illustrates the level", "the level of", "level of transcript", "of transcript complexity", "transcript complexity and", "complexity and functional", "and functional specificity", "functional specificity that", "specificity that such", "that such \\general\\", "such \\general\\ transcriptional", "\\general\\ transcriptional cofactors", "transcriptional cofactors can", "cofactors can have.", "the notch hlh transcription", "notch hlh transcription pathway:", "transcription pathway:

", "pathway:

notch", "

notch signaling was", "notch signaling was first", "signaling was first identified", "was first identified in", "first identified in drosophila", "in drosophila where", "drosophila where it", "where it has been", "it has been studied", "has been studied in", "been studied in detail", "studied in detail at", "in detail at the", "detail at the genetic", "the genetic molecular", "molecular biochemical and", "biochemical and cellular levels", "cellular levels reviewed", "levels reviewed in", "in justice 2002", "louvri 2006 .", ". in drosophila", "in drosophila notch", "drosophila notch signaling", "notch signaling to the", "signaling to the nucleus", "to the nucleus is", "the nucleus is thought", "nucleus is thought always", "is thought always to", "thought always to be", "always to be mediated", "to be mediated by", "be mediated by one", "mediated by one specific", "by one specific dna", "one specific dna binding", "specific dna binding transcription", "dna binding transcription factor", "transcription factor suppressor", "factor suppressor of", "of hairless. in", "hairless. in mammals", "in mammals the", "mammals the homologous", "the homologous genes are", "homologous genes are called", "genes are called cbf1", "called cbf1 or", "cbf1 or rbpjkappa", "rbpjkappa while", "while in worms they", "in worms they are", "worms they are called", "they are called lag", "are called lag 1", "lag 1 so", "1 so that", "so that the acronym", "that the acronym \\csl\\", "the acronym \\csl\\ has", "acronym \\csl\\ has been", "\\csl\\ has been given", "has been given to", "been given to this", "given to this conserved", "to this conserved transcription", "this conserved transcription factor", "conserved transcription factor family.", "factor family. there", "family. there are", "there are at least", "are at least two", "at least two human", "least two human csl", "two human csl homologues", "csl homologues which", "homologues which are", "which are now named", "are now named rbpj", "now named rbpj and", "named rbpj and rbpjl.

csl", "rbpj and rbpjl.

csl is", "and rbpjl.

csl is an", "rbpjl.

csl is an example", "is an example of", "an example of a", "example of a bifunctional", "of a bifunctional dna", "a bifunctional dna binding", "bifunctional dna binding transcription", "binding transcription factor that", "transcription factor that mediates", "factor that mediates repression", "that mediates repression of", "mediates repression of specific", "repression of specific target", "of specific target genes", "specific target genes in", "target genes in one", "genes in one context", "one context but", "context but activation", "but activation of the", "activation of the same", "of the same targets", "the same targets in", "same targets in another", "targets in another context.", "another context. this", "context. this bifunctionality", "this bifunctionality is mediated", "bifunctionality is mediated by", "is mediated by the", "mediated by the association", "by the association of", "the association of specific", "association of specific co", "of specific co repressor", "specific co repressor complexes", "co repressor complexes vs.", "repressor complexes vs. specific", "complexes vs. specific co", "vs. specific co activator", "specific co activator complexes", "co activator complexes in", "activator complexes in different", "complexes in different contexts", "different contexts namely", "contexts namely in", "namely in the absence", "in the absence or", "the absence or presence", "absence or presence of", "or presence of notch", "presence of notch signaling.

in", "of notch signaling.

in drosophila", "signaling.

in drosophila su", "drosophila su h", "su h represses", "h represses target", "represses target gene transcription", "target gene transcription in", "gene transcription in the", "transcription in the absence", "in the absence of", "the absence of notch", "absence of notch signaling", "notch signaling but", "signaling but activates", "but activates target genes", "activates target genes during", "target genes during notch", "genes during notch signaling.", "notch signaling. at", "signaling. at least", "at least some of", "least some of the", "some of the mammalian", "of the mammalian csl", "the mammalian csl homologues", "mammalian csl homologues are", "csl homologues are believed", "homologues are believed also", "are believed also to", "believed also to be", "also to be bifunctional", "be bifunctional and", "bifunctional and to", "and to mediate target", "to mediate target gene", "mediate target gene repression", "target gene repression in", "gene repression in the", "repression in the absence", "notch signaling and", "signaling and activation", "and activation in the", "activation in the presence", "in the presence of", "the presence of notch", "presence of notch signaling.

notch", "of notch signaling.

notch co", "notch signaling.

notch co activator", "signaling.

notch co activator and", "co activator and co", "activator and co repressor", "and co repressor complexes:", "co repressor complexes: this", "repressor complexes: this repression", "complexes: this repression is", "this repression is mediated", "repression is mediated by", "is mediated by at", "mediated by at least", "by at least one", "at least one specific", "least one specific co", "one specific co repressor", "repressor complexes co", "complexes co r", "co r bound", "r bound to", "bound to csl in", "to csl in the", "csl in the absence", "absence of notch signaling.", "notch signaling. in", "signaling. in drosophila", "in drosophila this", "drosophila this co", "this co repressor complex", "co repressor complex consists", "repressor complex consists of", "complex consists of at", "consists of at least", "of at least three", "at least three distinct", "least three distinct co", "three distinct co repressor", "distinct co repressor proteins:", "co repressor proteins: hairless", "proteins: hairless groucho", "and dctbp drosophila", "dctbp drosophila c", "drosophila c terminal binding", "c terminal binding protein", "terminal binding protein .", "protein . hairless", ". hairless has", "hairless has been show", "has been show to", "been show to bind", "show to bind directly", "to bind directly to", "bind directly to su", "directly to su h", "h and", "and groucho and dctbp", "groucho and dctbp have", "and dctbp have been", "dctbp have been shown", "have been shown to", "been shown to bind", "shown to bind directly", "bind directly to hairless", "to hairless barolo", "barolo 2002 .", "2002 . all", ". all three", "all three of the", "three of the co", "of the co repressor", "the co repressor proteins", "co repressor proteins have", "repressor proteins have been", "proteins have been shown", "been shown to be", "shown to be necessary", "to be necessary for", "be necessary for proper", "necessary for proper gene", "for proper gene regulation", "proper gene regulation during", "gene regulation during notch", "regulation during notch signaling", "during notch signaling in", "notch signaling in vivo", "in vivo nagel", "nagel 2005 .

in", ".

in mammals the", "mammals the same", "the same general pathway", "same general pathway and", "general pathway and mechanisms", "pathway and mechanisms are", "and mechanisms are observed", "are observed where", "observed where csl", "where csl proteins are", "csl proteins are bifunctional", "proteins are bifunctional dna", "are bifunctional dna binding", "dna binding transcription factors", "transcription factors tfs", "tfs that", "that bind to co", "bind to co repressor", "to co repressor complexes", "co repressor complexes to", "repressor complexes to mediate", "complexes to mediate repression", "to mediate repression in", "mediate repression in the", "signaling and bind", "and bind to co", "bind to co activator", "activator complexes to", "complexes to mediate activation", "to mediate activation in", "mediate activation in the", "presence of notch signaling.", "notch signaling. however", "however in mammals", "in mammals there", "mammals there may", "there may be multiple", "may be multiple co", "be multiple co repressor", "multiple co repressor complexes", "repressor complexes rather", "complexes rather than", "rather than the single", "than the single hairless", "the single hairless co", "single hairless co repressor", "hairless co repressor complex", "co repressor complex that", "repressor complex that has", "complex that has been", "that has been observed", "has been observed in", "been observed in drosophila.", "in drosophila.

during", "drosophila.

during notch", "

during notch signaling in", "notch signaling in all", "signaling in all systems", "all systems the", "systems the notch", "the notch transmembrane receptor", "notch transmembrane receptor is", "transmembrane receptor is cleaved", "receptor is cleaved and", "is cleaved and the", "cleaved and the notch", "and the notch intracellular", "the notch intracellular domain", "intracellular domain nicd", "nicd translocates to", "translocates to the nucleus", "the nucleus where", "nucleus where it", "where it there functions", "it there functions as", "there functions as a", "functions as a specific", "as a specific transcription", "a specific transcription co", "specific transcription co activator", "transcription co activator for", "co activator for csl", "activator for csl proteins.", "csl proteins. in", "proteins. in the", "the nucleus nicd", "nucleus nicd replaces", "nicd replaces the co", "replaces the co r", "the co r complex", "co r complex bound", "r complex bound to", "complex bound to csl", "to csl thus", "csl thus resulting", "thus resulting in de", "resulting in de repression", "in de repression of", "repression of notch", "of notch target", "notch target genes in", "target genes in the", "genes in the nucleus.", "the nucleus. once", "nucleus. once bound", "once bound to csl", "to csl nicd", "csl nicd and", "nicd and csl proteins", "and csl proteins recruit", "csl proteins recruit an", "proteins recruit an additional", "recruit an additional co", "an additional co activator", "additional co activator protein", "activator protein mastermind", "mastermind to form", "to form a csl", "form a csl nicd", "a csl nicd mam", "csl nicd mam ternary", "nicd mam ternary co", "mam ternary co activator", "co activator co", "activator co a", "co a complex.", "complex. this co", "this co a complex", "co a complex was", "a complex was initially", "complex was initially thought", "was initially thought to", "initially thought to be", "thought to be sufficient", "to be sufficient to", "be sufficient to mediate", "sufficient to mediate activation", "to mediate activation of", "activation of at", "at least some notch", "least some notch target", "some notch target genes.", "target genes. however", "however there now", "there now is evidence", "now is evidence that", "is evidence that still", "evidence that still other", "that still other co", "still other co activators", "other co activators and", "co activators and additional", "activators and additional dna", "and additional dna binding", "additional dna binding transcription", "binding transcription factors are", "transcription factors are required", "factors are required in", "are required in at", "required in at least", "in at least some", "at least some contexts", "some contexts reviewed", "contexts reviewed in", "in barolo 2002", "barolo 2002 .

mammalian", "2002 .

mammalian csl corepressor", ".

mammalian csl corepressor complexes:", "csl corepressor complexes: in", "corepressor complexes: in the", "complexes: in the absence", "the absence of activated", "absence of activated notch", "of activated notch signaling", "notch signaling dna", "signaling dna bound", "dna bound csl proteins", "bound csl proteins recruit", "csl proteins recruit a", "proteins recruit a corepressor", "recruit a corepressor complex", "a corepressor complex to", "corepressor complex to maintain", "complex to maintain target", "to maintain target genes", "maintain target genes in", "genes in the repressed", "in the repressed state", "the repressed state until", "repressed state until notch", "state until notch is", "until notch is specifically", "notch is specifically activated.", "is specifically activated. the", "specifically activated. the mammalian", "activated. the mammalian corepressor", "the mammalian corepressor complexes", "mammalian corepressor complexes include", "corepressor complexes include ncor", "complexes include ncor complexes", "ncor complexes but", "complexes but may", "but may also include", "may also include additional", "also include additional corepressor", "include additional corepressor proteins", "corepressor proteins such", "proteins such as", "as sharp reviewed", "sharp reviewed in", "in mumm 2000", "mumm 2000 and", "and kovall 2007", "kovall 2007 .", "2007 . the exact", ". the exact composition", "the exact composition of", "exact composition of the", "composition of the csl", "of the csl ncor", "the csl ncor complex", "csl ncor complex is", "ncor complex is not", "complex is not known", "not known but", "known but in", "but in other pathways", "in other pathways the", "other pathways the \\core\\", "pathways the \\core\\ ncor", "the \\core\\ ncor corepressor", "\\core\\ ncor corepressor complex", "ncor corepressor complex includes", "corepressor complex includes at", "complex includes at least", "includes at least one", "at least one ncor", "least one ncor protein", "ncor protein ncor1", "cir one", "one histone deacetylase protein", "deacetylase protein hdac1", "etc and", "and one tbl1 protein", "tbl1 protein tbl1x", "tbl1xr1 reviewed", "in rosenfeld 2006", "rosenfeld 2006 .", "2006 . in some", ". in some contexts", "some contexts the", "contexts the core", "the core ncor corepressor", "core ncor corepressor complex", "ncor corepressor complex may", "corepressor complex may also", "complex may also recruit", "may also recruit additional", "also recruit additional corepressor", "recruit additional corepressor proteins", "additional corepressor proteins or", "corepressor proteins or complexes", "or complexes such", "complexes such as", "such as the sin3", "as the sin3 complex", "sin3 complex which", "complex which consists", "which consists of sin3", "of sin3 sin3a", "sin3b and", "and sap30 or", "sap30 or other", "or other sin3 associated", "other sin3 associated proteins.", "sin3 associated proteins. an", "associated proteins. an additional", "proteins. an additional csl", "binding corepressor sharp", "sharp may also", "may also contribute to", "also contribute to the", "contribute to the csl", "to the csl corepressor", "the csl corepressor complex", "csl corepressor complex in", "corepressor complex in some", "complex in some contexts", "some contexts oswald", "oswald 2002 .", "2002 . the csl", ". the csl corepressor", "csl corepressor complex also", "corepressor complex also includes", "complex also includes a", "also includes a bifunctional", "includes a bifunctional cofactor", "bifunctional cofactor skip", "skip that is", "that is present in", "is present in both", "present in both csl", "in both csl corepressor", "both csl corepressor complexes", "csl corepressor complexes and", "corepressor complexes and csl", "complexes and csl coactivator", "and csl coactivator complexes", "coactivator complexes and", "complexes and may", "and may function in", "may function in the", "function in the binding", "in the binding of", "the binding of nicd", "binding of nicd and", "of nicd and displacement", "nicd and displacement of", "and displacement of the", "displacement of the corepressor", "of the corepressor complex", "the corepressor complex during", "corepressor complex during activated", "complex during activated notch", "during activated notch signaling", "notch signaling zhou", "zhou 2000 .

mammalian", "2000 .

mammalian csl coactivator", ".

mammalian csl coactivator complexes:", "csl coactivator complexes: upon", "coactivator complexes: upon activation", "complexes: upon activation of", "upon activation of notch", "activation of notch signaling", "notch signaling cleavage", "signaling cleavage of", "cleavage of the transmembrane", "of the transmembrane notch", "the transmembrane notch receptor", "transmembrane notch receptor releases", "notch receptor releases the", "receptor releases the notch", "releases the notch intracellular", "nicd which", "which translocates to the", "where it binds to", "it binds to csl", "binds to csl and", "to csl and displaces", "csl and displaces the", "and displaces the corepressor", "displaces the corepressor complex", "the corepressor complex from", "corepressor complex from csl", "from csl reviewed", "csl reviewed in", "2007 . the resulting", ". the resulting csl", "the resulting csl nicd", "resulting csl nicd \\binary", "csl nicd \\binary complex\\", "nicd \\binary complex\\ then", "\\binary complex\\ then recruits", "complex\\ then recruits an", "then recruits an additional", "recruits an additional coactivator", "additional coactivator mastermind", "mam to", "to form a ternary", "form a ternary complex.", "a ternary complex. the", "ternary complex. the ternary", "complex. the ternary complex", "the ternary complex then", "ternary complex then recruits", "complex then recruits additional", "recruits additional more", "additional more general", "general coactivators such", "coactivators such as", "such as creb binding", "as creb binding protein", "binding protein cbp", "cbp or", "or the related p300", "the related p300 coactivator", "p300 coactivator and", "coactivator and a", "and a number of", "a number of histone", "number of histone acetytransferase", "histone acetytransferase hat", "proteins including gcn5", "including gcn5 and pcaf", "and pcaf fryer", "fryer 2002 .", "2002 . there is", ". there is evidence", "there is evidence that", "is evidence that mam", "evidence that mam also", "that mam also can", "mam also can subsequently", "also can subsequently recruit", "can subsequently recruit specific", "subsequently recruit specific kinases", "recruit specific kinases that", "specific kinases that phosphorylate", "kinases that phosphorylate nicd", "phosphorylate nicd to", "nicd to downregulate", "to downregulate its function", "downregulate its function and", "its function and turn", "function and turn off", "and turn off notch", "turn off notch signaling", "notch signaling fryer", "fryer 2004 .

combinatorial", "2004 .

combinatorial complexity in", ".

combinatorial complexity in transcription", "complexity in transcription cofactor", "in transcription cofactor complexes:", "transcription cofactor complexes: hdac9", "cofactor complexes: hdac9 has", "complexes: hdac9 has at", "hdac9 has at least", "has at least 7", "at least 7 splice", "least 7 splice isoforms", "splice isoforms with", "isoforms with some", "with some having distinct", "some having distinct interaction", "having distinct interaction and", "distinct interaction and functional", "interaction and functional properties.", "and functional properties. isoforms", "functional properties. isoforms 6", "properties. isoforms 6 and", "isoforms 6 and 7", "6 and 7 interact", "and 7 interact with", "7 interact with ncor1.", "interact with ncor1. isoforms", "with ncor1. isoforms 1", "ncor1. isoforms 1 and", "isoforms 1 and 4", "1 and 4 interact", "and 4 interact with", "4 interact with mef2", "with mef2 sparrow", "1999 which", "which is a specific", "is a specific dna", "a specific dna binding", "specific dna binding cofactor", "dna binding cofactor for", "binding cofactor for a", "cofactor for a subset", "for a subset of", "a subset of hlh", "subset of hlh proteins.", "of hlh proteins. isoform", "hlh proteins. isoform 3", "proteins. isoform 3 interacts", "isoform 3 interacts with", "3 interacts with both", "interacts with both ncor1", "with both ncor1 and", "both ncor1 and mef2.", "ncor1 and mef2. although", "and mef2. although many", "mef2. although many hdacs", "although many hdacs only", "many hdacs only have", "hdacs only have one", "only have one or", "have one or two", "one or two isoforms", "two isoforms this", "isoforms this complexity", "this complexity for hdac9", "complexity for hdac9 illustrates", "for hdac9 illustrates the", "hdac9 illustrates the level", "illustrates the level of", "the level of transcript", "level of transcript complexity", "of transcript complexity and", "transcript complexity and functional", "complexity and functional specificity", "and functional specificity that", "functional specificity that such", "specificity that such \\general\\", "that such \\general\\ transcriptional", "such \\general\\ transcriptional cofactors", "\\general\\ transcriptional cofactors can", "transcriptional cofactors can have.", "the notch hlh transcription pathway:", "hlh transcription pathway:

", "transcription pathway:

notch", "pathway:

notch signaling", "

notch signaling was first", "notch signaling was first identified", "signaling was first identified in", "was first identified in drosophila", "identified in drosophila where", "in drosophila where it", "drosophila where it has", "where it has been studied", "it has been studied in", "has been studied in detail", "been studied in detail at", "studied in detail at the", "in detail at the genetic", "at the genetic molecular", "genetic molecular biochemical", "molecular biochemical and cellular", "and cellular levels reviewed", "cellular levels reviewed in", "levels reviewed in justice", "reviewed in justice 2002", "justice 2002 bray", "2002 bray 2006", "bray 2006 schweisguth", "2006 schweisguth 2004", "schweisguth 2004 louvri", "2004 louvri 2006", "2006 . in drosophila", "in drosophila notch signaling", "drosophila notch signaling to", "notch signaling to the nucleus", "signaling to the nucleus is", "to the nucleus is thought", "the nucleus is thought always", "nucleus is thought always to", "is thought always to be", "thought always to be mediated", "always to be mediated by", "to be mediated by one", "be mediated by one specific", "mediated by one specific dna", "by one specific dna binding", "one specific dna binding transcription", "specific dna binding transcription factor", "binding transcription factor suppressor", "transcription factor suppressor of", "factor suppressor of hairless.", "suppressor of hairless. in", "of hairless. in mammals", "in mammals the homologous", "mammals the homologous genes", "the homologous genes are called", "homologous genes are called cbf1", "are called cbf1 or", "called cbf1 or rbpjkappa", "or rbpjkappa while", "rbpjkappa while in", "while in worms they are", "in worms they are called", "worms they are called lag", "they are called lag 1", "called lag 1 so", "lag 1 so that", "1 so that the", "so that the acronym \\csl\\", "that the acronym \\csl\\ has", "the acronym \\csl\\ has been", "acronym \\csl\\ has been given", "\\csl\\ has been given to", "has been given to this", "been given to this conserved", "given to this conserved transcription", "to this conserved transcription factor", "this conserved transcription factor family.", "transcription factor family. there", "factor family. there are", "family. there are at", "there are at least two", "are at least two human", "at least two human csl", "least two human csl homologues", "human csl homologues which", "csl homologues which are", "homologues which are now", "which are now named rbpj", "are now named rbpj and", "now named rbpj and rbpjl.

csl", "named rbpj and rbpjl.

csl is", "rbpj and rbpjl.

csl is an", "and rbpjl.

csl is an example", "rbpjl.

csl is an example of", "is an example of a", "an example of a bifunctional", "example of a bifunctional dna", "of a bifunctional dna binding", "a bifunctional dna binding transcription", "bifunctional dna binding transcription factor", "dna binding transcription factor that", "binding transcription factor that mediates", "transcription factor that mediates repression", "factor that mediates repression of", "that mediates repression of specific", "mediates repression of specific target", "repression of specific target genes", "of specific target genes in", "specific target genes in one", "target genes in one context", "in one context but", "one context but activation", "context but activation of", "but activation of the same", "activation of the same targets", "of the same targets in", "the same targets in another", "same targets in another context.", "in another context. this", "another context. this bifunctionality", "context. this bifunctionality is", "this bifunctionality is mediated by", "bifunctionality is mediated by the", "is mediated by the association", "mediated by the association of", "by the association of specific", "the association of specific co", "association of specific co repressor", "of specific co repressor complexes", "specific co repressor complexes vs.", "co repressor complexes vs. specific", "repressor complexes vs. specific co", "complexes vs. specific co activator", "vs. specific co activator complexes", "specific co activator complexes in", "co activator complexes in different", "activator complexes in different contexts", "in different contexts namely", "different contexts namely in", "contexts namely in the", "namely in the absence or", "in the absence or presence", "the absence or presence of", "absence or presence of notch", "or presence of notch signaling.

in", "presence of notch signaling.

in drosophila", "notch signaling.

in drosophila su", "signaling.

in drosophila su h", "su h represses target", "h represses target gene", "represses target gene transcription in", "target gene transcription in the", "gene transcription in the absence", "transcription in the absence of", "in the absence of notch", "the absence of notch signaling", "of notch signaling but", "notch signaling but activates", "signaling but activates target", "but activates target genes during", "activates target genes during notch", "target genes during notch signaling.", "during notch signaling. at", "notch signaling. at least", "signaling. at least some", "at least some of the", "least some of the mammalian", "some of the mammalian csl", "of the mammalian csl homologues", "the mammalian csl homologues are", "mammalian csl homologues are believed", "csl homologues are believed also", "homologues are believed also to", "are believed also to be", "believed also to be bifunctional", "to be bifunctional and", "be bifunctional and to", "bifunctional and to mediate", "and to mediate target gene", "to mediate target gene repression", "mediate target gene repression in", "target gene repression in the", "gene repression in the absence", "repression in the absence of", "of notch signaling and", "notch signaling and activation", "signaling and activation in", "and activation in the presence", "activation in the presence of", "in the presence of notch", "the presence of notch signaling.

notch", "presence of notch signaling.

notch co", "of notch signaling.

notch co activator", "notch signaling.

notch co activator and", "signaling.

notch co activator and co", "co activator and co repressor", "activator and co repressor complexes:", "and co repressor complexes: this", "co repressor complexes: this repression", "repressor complexes: this repression is", "complexes: this repression is mediated", "this repression is mediated by", "repression is mediated by at", "is mediated by at least", "mediated by at least one", "by at least one specific", "at least one specific co", "least one specific co repressor", "one specific co repressor complexes", "co repressor complexes co", "repressor complexes co r", "co r bound to", "r bound to csl", "bound to csl in the", "to csl in the absence", "csl in the absence of", "the absence of notch signaling.", "of notch signaling. in", "notch signaling. in drosophila", "in drosophila this co", "drosophila this co repressor", "this co repressor complex consists", "co repressor complex consists of", "repressor complex consists of at", "complex consists of at least", "consists of at least three", "of at least three distinct", "at least three distinct co", "least three distinct co repressor", "three distinct co repressor proteins:", "distinct co repressor proteins: hairless", "repressor proteins: hairless groucho", "hairless groucho and", "and dctbp drosophila c", "dctbp drosophila c terminal", "drosophila c terminal binding protein", "c terminal binding protein .", "binding protein . hairless", "protein . hairless has", ". hairless has been", "hairless has been show to", "has been show to bind", "been show to bind directly", "show to bind directly to", "to bind directly to su", "bind directly to su h", "su h and", "h and groucho", "and groucho and dctbp have", "groucho and dctbp have been", "and dctbp have been shown", "dctbp have been shown to", "have been shown to bind", "been shown to bind directly", "shown to bind directly to", "to bind directly to hairless", "directly to hairless barolo", "hairless barolo 2002", "2002 . all three", ". all three of", "all three of the co", "three of the co repressor", "of the co repressor proteins", "the co repressor proteins have", "co repressor proteins have been", "repressor proteins have been shown", "proteins have been shown to", "have been shown to be", "been shown to be necessary", "shown to be necessary for", "to be necessary for proper", "be necessary for proper gene", "necessary for proper gene regulation", "for proper gene regulation during", "proper gene regulation during notch", "gene regulation during notch signaling", "regulation during notch signaling in", "during notch signaling in vivo", "signaling in vivo nagel", "vivo nagel 2005", "nagel 2005 .

in mammals", "2005 .

in mammals the", ".

in mammals the same", "mammals the same general", "the same general pathway and", "same general pathway and mechanisms", "general pathway and mechanisms are", "pathway and mechanisms are observed", "mechanisms are observed where", "are observed where csl", "observed where csl proteins", "where csl proteins are bifunctional", "csl proteins are bifunctional dna", "proteins are bifunctional dna binding", "are bifunctional dna binding transcription", "bifunctional dna binding transcription factors", "binding transcription factors tfs", "tfs that bind", "that bind to co repressor", "bind to co repressor complexes", "to co repressor complexes to", "co repressor complexes to mediate", "repressor complexes to mediate repression", "complexes to mediate repression in", "to mediate repression in the", "mediate repression in the absence", "notch signaling and bind", "signaling and bind to", "and bind to co activator", "to co activator complexes", "co activator complexes to", "activator complexes to mediate", "complexes to mediate activation in", "to mediate activation in the", "mediate activation in the presence", "the presence of notch signaling.", "of notch signaling. however", "signaling. however in", "in mammals there may", "mammals there may be", "there may be multiple co", "may be multiple co repressor", "be multiple co repressor complexes", "co repressor complexes rather", "repressor complexes rather than", "complexes rather than the", "rather than the single hairless", "than the single hairless co", "the single hairless co repressor", "single hairless co repressor complex", "hairless co repressor complex that", "co repressor complex that has", "repressor complex that has been", "complex that has been observed", "that has been observed in", "has been observed in drosophila.", "observed in drosophila.

during", "in drosophila.

during notch", "drosophila.

during notch signaling", "

during notch signaling in all", "notch signaling in all systems", "in all systems the", "all systems the notch", "systems the notch transmembrane", "the notch transmembrane receptor is", "notch transmembrane receptor is cleaved", "transmembrane receptor is cleaved and", "receptor is cleaved and the", "is cleaved and the notch", "cleaved and the notch intracellular", "and the notch intracellular domain", "notch intracellular domain nicd", "domain nicd translocates", "nicd translocates to the", "to the nucleus where", "the nucleus where it", "nucleus where it there", "where it there functions as", "it there functions as a", "there functions as a specific", "functions as a specific transcription", "as a specific transcription co", "a specific transcription co activator", "specific transcription co activator for", "transcription co activator for csl", "co activator for csl proteins.", "for csl proteins. in", "csl proteins. in the", "proteins. in the nucleus", "in the nucleus nicd", "the nucleus nicd replaces", "nucleus nicd replaces the", "nicd replaces the co r", "replaces the co r complex", "the co r complex bound", "co r complex bound to", "r complex bound to csl", "bound to csl thus", "to csl thus resulting", "csl thus resulting in", "thus resulting in de repression", "resulting in de repression of", "de repression of notch", "repression of notch target", "of notch target genes", "notch target genes in the", "target genes in the nucleus.", "in the nucleus. once", "the nucleus. once bound", "nucleus. once bound to", "bound to csl nicd", "to csl nicd and", "csl nicd and csl", "nicd and csl proteins recruit", "and csl proteins recruit an", "csl proteins recruit an additional", "proteins recruit an additional co", "recruit an additional co activator", "an additional co activator protein", "co activator protein mastermind", "protein mastermind to", "mastermind to form a", "to form a csl nicd", "form a csl nicd mam", "a csl nicd mam ternary", "csl nicd mam ternary co", "nicd mam ternary co activator", "ternary co activator co", "co activator co a", "a complex. this", "complex. this co a", "this co a complex was", "co a complex was initially", "a complex was initially thought", "complex was initially thought to", "was initially thought to be", "initially thought to be sufficient", "thought to be sufficient to", "to be sufficient to mediate", "be sufficient to mediate activation", "sufficient to mediate activation of", "mediate activation of at", "activation of at least", "of at least some", "at least some notch target", "least some notch target genes.", "notch target genes. however", "genes. however there", "however there now is", "there now is evidence that", "now is evidence that still", "is evidence that still other", "evidence that still other co", "that still other co activators", "still other co activators and", "other co activators and additional", "co activators and additional dna", "activators and additional dna binding", "and additional dna binding transcription", "additional dna binding transcription factors", "dna binding transcription factors are", "binding transcription factors are required", "transcription factors are required in", "factors are required in at", "are required in at least", "required in at least some", "in at least some contexts", "least some contexts reviewed", "some contexts reviewed in", "contexts reviewed in barolo", "reviewed in barolo 2002", "in barolo 2002 .

mammalian", "barolo 2002 .

mammalian csl", "2002 .

mammalian csl corepressor complexes:", ".

mammalian csl corepressor complexes: in", "csl corepressor complexes: in the", "corepressor complexes: in the absence", "complexes: in the absence of", "in the absence of activated", "the absence of activated notch", "absence of activated notch signaling", "activated notch signaling dna", "notch signaling dna bound", "signaling dna bound csl", "dna bound csl proteins recruit", "bound csl proteins recruit a", "csl proteins recruit a corepressor", "proteins recruit a corepressor complex", "recruit a corepressor complex to", "a corepressor complex to maintain", "corepressor complex to maintain target", "complex to maintain target genes", "to maintain target genes in", "maintain target genes in the", "target genes in the repressed", "genes in the repressed state", "in the repressed state until", "the repressed state until notch", "repressed state until notch is", "state until notch is specifically", "until notch is specifically activated.", "notch is specifically activated. the", "is specifically activated. the mammalian", "specifically activated. the mammalian corepressor", "activated. the mammalian corepressor complexes", "the mammalian corepressor complexes include", "mammalian corepressor complexes include ncor", "corepressor complexes include ncor complexes", "include ncor complexes but", "ncor complexes but may", "complexes but may also", "but may also include additional", "may also include additional corepressor", "also include additional corepressor proteins", "additional corepressor proteins such", "corepressor proteins such as", "proteins such as sharp", "such as sharp reviewed", "as sharp reviewed in", "sharp reviewed in mumm", "reviewed in mumm 2000", "in mumm 2000 and", "mumm 2000 and kovall", "2000 and kovall 2007", "and kovall 2007 .", "kovall 2007 . the", "2007 . the exact composition", ". the exact composition of", "the exact composition of the", "exact composition of the csl", "composition of the csl ncor", "of the csl ncor complex", "the csl ncor complex is", "csl ncor complex is not", "ncor complex is not known", "is not known but", "not known but in", "known but in other", "but in other pathways the", "in other pathways the \\core\\", "other pathways the \\core\\ ncor", "pathways the \\core\\ ncor corepressor", "the \\core\\ ncor corepressor complex", "\\core\\ ncor corepressor complex includes", "ncor corepressor complex includes at", "corepressor complex includes at least", "complex includes at least one", "includes at least one ncor", "at least one ncor protein", "one ncor protein ncor1", "protein ncor1 ncor2", "ncor1 ncor2 cir", "cir one histone", "histone deacetylase protein hdac1", "protein hdac1 hdac2", "hdac1 hdac2 hdac3", "hdac2 hdac3 etc", "etc and one", "one tbl1 protein tbl1x", "protein tbl1x tbl1xr1", "tbl1xr1 reviewed in", "reviewed in rosenfeld 2006", "in rosenfeld 2006 .", "rosenfeld 2006 . in", "2006 . in some contexts", "in some contexts the", "some contexts the core", "contexts the core ncor", "the core ncor corepressor complex", "core ncor corepressor complex may", "ncor corepressor complex may also", "corepressor complex may also recruit", "complex may also recruit additional", "may also recruit additional corepressor", "also recruit additional corepressor proteins", "recruit additional corepressor proteins or", "additional corepressor proteins or complexes", "proteins or complexes such", "or complexes such as", "complexes such as the", "such as the sin3 complex", "the sin3 complex which", "sin3 complex which consists", "complex which consists of", "consists of sin3 sin3a", "sin3 sin3a sin3b", "sin3b and sap30", "and sap30 or other", "sap30 or other sin3", "or other sin3 associated proteins.", "other sin3 associated proteins. an", "sin3 associated proteins. an additional", "associated proteins. an additional csl", "additional csl ncor", "csl ncor binding", "ncor binding corepressor sharp", "corepressor sharp may", "sharp may also contribute", "may also contribute to the", "also contribute to the csl", "contribute to the csl corepressor", "to the csl corepressor complex", "the csl corepressor complex in", "csl corepressor complex in some", "corepressor complex in some contexts", "in some contexts oswald", "contexts oswald 2002", "oswald 2002 . the", "2002 . the csl corepressor", ". the csl corepressor complex", "the csl corepressor complex also", "csl corepressor complex also includes", "corepressor complex also includes a", "complex also includes a bifunctional", "also includes a bifunctional cofactor", "a bifunctional cofactor skip", "cofactor skip that", "skip that is present", "that is present in both", "is present in both csl", "present in both csl corepressor", "in both csl corepressor complexes", "both csl corepressor complexes and", "csl corepressor complexes and csl", "corepressor complexes and csl coactivator", "complexes and csl coactivator complexes", "csl coactivator complexes and", "coactivator complexes and may", "complexes and may function", "and may function in the", "may function in the binding", "function in the binding of", "in the binding of nicd", "the binding of nicd and", "binding of nicd and displacement", "of nicd and displacement of", "nicd and displacement of the", "and displacement of the corepressor", "displacement of the corepressor complex", "of the corepressor complex during", "the corepressor complex during activated", "corepressor complex during activated notch", "complex during activated notch signaling", "activated notch signaling zhou", "signaling zhou 2000", "zhou 2000 .

mammalian csl", "2000 .

mammalian csl coactivator complexes:", ".

mammalian csl coactivator complexes: upon", "csl coactivator complexes: upon activation", "coactivator complexes: upon activation of", "complexes: upon activation of notch", "upon activation of notch signaling", "of notch signaling cleavage", "notch signaling cleavage of", "signaling cleavage of the", "cleavage of the transmembrane notch", "of the transmembrane notch receptor", "the transmembrane notch receptor releases", "transmembrane notch receptor releases the", "notch receptor releases the notch", "receptor releases the notch intracellular", "releases the notch intracellular domain", "nicd which translocates", "which translocates to the nucleus", "nucleus where it binds", "where it binds to csl", "it binds to csl and", "binds to csl and displaces", "to csl and displaces the", "csl and displaces the corepressor", "and displaces the corepressor complex", "displaces the corepressor complex from", "the corepressor complex from csl", "complex from csl reviewed", "from csl reviewed in", "csl reviewed in mumm", "2007 . the resulting csl", ". the resulting csl nicd", "the resulting csl nicd \\binary", "resulting csl nicd \\binary complex\\", "csl nicd \\binary complex\\ then", "nicd \\binary complex\\ then recruits", "\\binary complex\\ then recruits an", "complex\\ then recruits an additional", "then recruits an additional coactivator", "an additional coactivator mastermind", "coactivator mastermind mam", "mam to form", "to form a ternary complex.", "form a ternary complex. the", "a ternary complex. the ternary", "ternary complex. the ternary complex", "complex. the ternary complex then", "the ternary complex then recruits", "ternary complex then recruits additional", "then recruits additional more", "recruits additional more general", "additional more general coactivators", "more general coactivators such", "general coactivators such as", "coactivators such as creb", "such as creb binding protein", "creb binding protein cbp", "cbp or the", "or the related p300 coactivator", "related p300 coactivator and", "p300 coactivator and a", "coactivator and a number", "and a number of histone", "a number of histone acetytransferase", "of histone acetytransferase hat", "acetytransferase hat proteins", "hat proteins including", "proteins including gcn5 and", "gcn5 and pcaf fryer", "pcaf fryer 2002", "fryer 2002 . there", "2002 . there is evidence", ". there is evidence that", "there is evidence that mam", "is evidence that mam also", "evidence that mam also can", "that mam also can subsequently", "mam also can subsequently recruit", "also can subsequently recruit specific", "can subsequently recruit specific kinases", "subsequently recruit specific kinases that", "recruit specific kinases that phosphorylate", "specific kinases that phosphorylate nicd", "that phosphorylate nicd to", "phosphorylate nicd to downregulate", "nicd to downregulate its", "to downregulate its function and", "downregulate its function and turn", "its function and turn off", "function and turn off notch", "and turn off notch signaling", "off notch signaling fryer", "signaling fryer 2004", "fryer 2004 .

combinatorial complexity", "2004 .

combinatorial complexity in transcription", ".

combinatorial complexity in transcription cofactor", "complexity in transcription cofactor complexes:", "in transcription cofactor complexes: hdac9", "transcription cofactor complexes: hdac9 has", "cofactor complexes: hdac9 has at", "complexes: hdac9 has at least", "hdac9 has at least 7", "has at least 7 splice", "at least 7 splice isoforms", "7 splice isoforms with", "splice isoforms with some", "isoforms with some having", "with some having distinct interaction", "some having distinct interaction and", "having distinct interaction and functional", "distinct interaction and functional properties.", "interaction and functional properties. isoforms", "and functional properties. isoforms 6", "functional properties. isoforms 6 and", "properties. isoforms 6 and 7", "isoforms 6 and 7 interact", "6 and 7 interact with", "and 7 interact with ncor1.", "7 interact with ncor1. isoforms", "interact with ncor1. isoforms 1", "with ncor1. isoforms 1 and", "ncor1. isoforms 1 and 4", "isoforms 1 and 4 interact", "1 and 4 interact with", "and 4 interact with mef2", "interact with mef2 sparrow", "mef2 sparrow 1999", "1999 which is", "which is a specific dna", "is a specific dna binding", "a specific dna binding cofactor", "specific dna binding cofactor for", "dna binding cofactor for a", "binding cofactor for a subset", "cofactor for a subset of", "for a subset of hlh", "a subset of hlh proteins.", "subset of hlh proteins. isoform", "of hlh proteins. isoform 3", "hlh proteins. isoform 3 interacts", "proteins. isoform 3 interacts with", "isoform 3 interacts with both", "3 interacts with both ncor1", "interacts with both ncor1 and", "with both ncor1 and mef2.", "both ncor1 and mef2. although", "ncor1 and mef2. although many", "and mef2. although many hdacs", "mef2. although many hdacs only", "although many hdacs only have", "many hdacs only have one", "hdacs only have one or", "only have one or two", "have one or two isoforms", "or two isoforms this", "two isoforms this complexity", "isoforms this complexity for", "this complexity for hdac9 illustrates", "complexity for hdac9 illustrates the", "for hdac9 illustrates the level", "hdac9 illustrates the level of", "illustrates the level of transcript", "the level of transcript complexity", "level of transcript complexity and", "of transcript complexity and functional", "transcript complexity and functional specificity", "complexity and functional specificity that", "and functional specificity that such", "functional specificity that such \\general\\", "specificity that such \\general\\ transcriptional", "that such \\general\\ transcriptional cofactors", "such \\general\\ transcriptional cofactors can", "\\general\\ transcriptional cofactors can have." ] }, { "record_id": "GLY_000594_1_278", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "350562", "r hsa", "hsa 350562", "r hsa 350562" ] }, { "record_id": "GLY_000594_1_278", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of ornithine", "ornithine decarboxylase", "regulation of ornithine", "of ornithine decarboxylase", "decarboxylase odc", "regulation of ornithine decarboxylase", "ornithine decarboxylase odc", "of ornithine decarboxylase odc", "polyamines increase", "increase the", "the production", "production of", "of antizyme", "az .", ". the", "the carboxy", "carboxy terminal", "terminal half", "half of", "antizyme interacts", "interacts with", "with odc", "generating an", "an inactive", "inactive az:odc", "az:odc heterodimer", "heterodimer complex.", "complex. a", "a carboxy", "terminal domain", "domain of", "of odc", "is exposed", "exposed only", "only within", "within the", "the heterodimer", "and is", "is the", "the target", "target for", "for subsequent", "subsequent degradation.", "degradation. a", "a domain", "domain within", "the amino", "amino terminal", "terminal portion", "portion of", "antizyme provides", "provides a", "a function", "function needed", "needed for", "for efficient", "efficient degradation", "degradation of", "odc by", "by the", "the proteasome.", "proteasome.
the", "
the proteasome", "proteasome cycle", "cycle starts", "starts with", "with the", "the processing", "processing of", "of az:odc", "sequestering odc", "odc and", "and then", "then degrading", "degrading it", "it to", "to peptides", "peptides but", "but releasing", "releasing az.", "az. az", "participates in", "in additional", "additional rounds", "rounds of", "of binding", "binding and", "and degradation.", "degradation. antizyme", "antizyme mediated", "mediated inhibition", "inhibition and", "and destruction", "destruction of", "odc reduces", "reduces synthesis", "synthesis of", "of polyamines.", "antizyme also", "also inhibits", "inhibits polyamine", "polyamine transport", "transport into", "into the", "the cell.", "cell. antizyme", "antizyme production", "production is", "is reduced", "completing the", "the regulatory", "regulatory circuit", "2001 .
the", ".
the following", "following illustration", "illustration is", "is adapted", "adapted from", "from a", "a minireview", "minireview by", "by pegg", "j. biol.", "biol. chem.", "vol. 281", "issue 21", "14529 14532.", "polyamines increase the", "increase the production", "the production of", "production of antizyme", "antizyme az", "az . the", ". the carboxy", "the carboxy terminal", "carboxy terminal half", "terminal half of", "half of antizyme", "of antizyme interacts", "antizyme interacts with", "interacts with odc", "odc generating", "generating an inactive", "an inactive az:odc", "inactive az:odc heterodimer", "az:odc heterodimer complex.", "heterodimer complex. a", "complex. a carboxy", "a carboxy terminal", "carboxy terminal domain", "terminal domain of", "domain of odc", "odc is", "is exposed only", "exposed only within", "only within the", "within the heterodimer", "heterodimer and", "and is the", "is the target", "the target for", "target for subsequent", "for subsequent degradation.", "subsequent degradation. a", "degradation. a domain", "a domain within", "domain within the", "within the amino", "the amino terminal", "amino terminal portion", "terminal portion of", "portion of antizyme", "of antizyme provides", "antizyme provides a", "provides a function", "a function needed", "function needed for", "needed for efficient", "for efficient degradation", "efficient degradation of", "degradation of odc", "of odc by", "odc by the", "by the proteasome.", "the proteasome.
the", "proteasome.
the proteasome", "
the proteasome cycle", "proteasome cycle starts", "cycle starts with", "starts with the", "with the processing", "the processing of", "processing of az:odc", "az:odc sequestering", "sequestering odc and", "odc and then", "and then degrading", "then degrading it", "degrading it to", "it to peptides", "to peptides but", "peptides but releasing", "but releasing az.", "releasing az. az", "az participates", "participates in additional", "in additional rounds", "additional rounds of", "rounds of binding", "of binding and", "binding and degradation.", "and degradation. antizyme", "degradation. antizyme mediated", "antizyme mediated inhibition", "mediated inhibition and", "inhibition and destruction", "and destruction of", "destruction of odc", "of odc reduces", "odc reduces synthesis", "reduces synthesis of", "synthesis of polyamines.", "additionally antizyme", "antizyme also inhibits", "also inhibits polyamine", "inhibits polyamine transport", "polyamine transport into", "transport into the", "into the cell.", "the cell. antizyme", "cell. antizyme production", "antizyme production is", "production is reduced", "reduced completing", "completing the regulatory", "the regulatory circuit", "circuit coffino", "coffino 2001", "2001 .
the following", ".
the following illustration", "following illustration is", "illustration is adapted", "is adapted from", "adapted from a", "from a minireview", "a minireview by", "minireview by pegg", "pegg 2006", "2006 j.", "j. biol. chem.", "chem. vol.", "281 issue", "21 14529", "polyamines increase the production", "increase the production of", "the production of antizyme", "of antizyme az", "antizyme az .", "az . the carboxy", ". the carboxy terminal", "the carboxy terminal half", "carboxy terminal half of", "terminal half of antizyme", "half of antizyme interacts", "of antizyme interacts with", "antizyme interacts with odc", "with odc generating", "odc generating an", "generating an inactive az:odc", "an inactive az:odc heterodimer", "inactive az:odc heterodimer complex.", "az:odc heterodimer complex. a", "heterodimer complex. a carboxy", "complex. a carboxy terminal", "a carboxy terminal domain", "carboxy terminal domain of", "terminal domain of odc", "of odc is", "odc is exposed", "is exposed only within", "exposed only within the", "only within the heterodimer", "the heterodimer and", "heterodimer and is", "and is the target", "is the target for", "the target for subsequent", "target for subsequent degradation.", "for subsequent degradation. a", "subsequent degradation. a domain", "degradation. a domain within", "a domain within the", "domain within the amino", "within the amino terminal", "the amino terminal portion", "amino terminal portion of", "terminal portion of antizyme", "portion of antizyme provides", "of antizyme provides a", "antizyme provides a function", "provides a function needed", "a function needed for", "function needed for efficient", "needed for efficient degradation", "for efficient degradation of", "efficient degradation of odc", "degradation of odc by", "of odc by the", "odc by the proteasome.", "by the proteasome.
the", "the proteasome.
the proteasome", "proteasome.
the proteasome cycle", "
the proteasome cycle starts", "proteasome cycle starts with", "cycle starts with the", "starts with the processing", "with the processing of", "the processing of az:odc", "of az:odc sequestering", "az:odc sequestering odc", "sequestering odc and then", "odc and then degrading", "and then degrading it", "then degrading it to", "degrading it to peptides", "it to peptides but", "to peptides but releasing", "peptides but releasing az.", "but releasing az. az", "az. az participates", "az participates in", "participates in additional rounds", "in additional rounds of", "additional rounds of binding", "rounds of binding and", "of binding and degradation.", "binding and degradation. antizyme", "and degradation. antizyme mediated", "degradation. antizyme mediated inhibition", "antizyme mediated inhibition and", "mediated inhibition and destruction", "inhibition and destruction of", "and destruction of odc", "destruction of odc reduces", "of odc reduces synthesis", "odc reduces synthesis of", "reduces synthesis of polyamines.", "polyamines. additionally", "additionally antizyme also", "antizyme also inhibits polyamine", "also inhibits polyamine transport", "inhibits polyamine transport into", "polyamine transport into the", "transport into the cell.", "into the cell. antizyme", "the cell. antizyme production", "cell. antizyme production is", "antizyme production is reduced", "is reduced completing", "reduced completing the", "completing the regulatory circuit", "regulatory circuit coffino", "coffino 2001 .
the", "2001 .
the following illustration", ".
the following illustration is", "following illustration is adapted", "illustration is adapted from", "is adapted from a", "adapted from a minireview", "from a minireview by", "a minireview by pegg", "by pegg 2006", "2006 j. biol.", "biol. chem. vol.", "chem. vol. 281", "vol. 281 issue", "281 issue 21", "issue 21 14529", "21 14529 14532.", "polyamines increase the production of", "increase the production of antizyme", "production of antizyme az", "of antizyme az .", "antizyme az . the", "az . the carboxy terminal", ". the carboxy terminal half", "the carboxy terminal half of", "carboxy terminal half of antizyme", "terminal half of antizyme interacts", "half of antizyme interacts with", "of antizyme interacts with odc", "interacts with odc generating", "with odc generating an", "odc generating an inactive", "generating an inactive az:odc heterodimer", "an inactive az:odc heterodimer complex.", "inactive az:odc heterodimer complex. a", "az:odc heterodimer complex. a carboxy", "heterodimer complex. a carboxy terminal", "complex. a carboxy terminal domain", "a carboxy terminal domain of", "carboxy terminal domain of odc", "domain of odc is", "of odc is exposed", "odc is exposed only", "is exposed only within the", "exposed only within the heterodimer", "within the heterodimer and", "the heterodimer and is", "heterodimer and is the", "and is the target for", "is the target for subsequent", "the target for subsequent degradation.", "target for subsequent degradation. a", "for subsequent degradation. a domain", "subsequent degradation. a domain within", "degradation. a domain within the", "a domain within the amino", "domain within the amino terminal", "within the amino terminal portion", "the amino terminal portion of", "amino terminal portion of antizyme", "terminal portion of antizyme provides", "portion of antizyme provides a", "of antizyme provides a function", "antizyme provides a function needed", "provides a function needed for", "a function needed for efficient", "function needed for efficient degradation", "needed for efficient degradation of", "for efficient degradation of odc", "efficient degradation of odc by", "degradation of odc by the", "of odc by the proteasome.", "odc by the proteasome.
the", "by the proteasome.
the proteasome", "the proteasome.
the proteasome cycle", "proteasome.
the proteasome cycle starts", "
the proteasome cycle starts with", "proteasome cycle starts with the", "cycle starts with the processing", "starts with the processing of", "with the processing of az:odc", "processing of az:odc sequestering", "of az:odc sequestering odc", "az:odc sequestering odc and", "sequestering odc and then degrading", "odc and then degrading it", "and then degrading it to", "then degrading it to peptides", "degrading it to peptides but", "it to peptides but releasing", "to peptides but releasing az.", "peptides but releasing az. az", "releasing az. az participates", "az. az participates in", "az participates in additional", "participates in additional rounds of", "in additional rounds of binding", "additional rounds of binding and", "rounds of binding and degradation.", "of binding and degradation. antizyme", "binding and degradation. antizyme mediated", "and degradation. antizyme mediated inhibition", "degradation. antizyme mediated inhibition and", "antizyme mediated inhibition and destruction", "mediated inhibition and destruction of", "inhibition and destruction of odc", "and destruction of odc reduces", "destruction of odc reduces synthesis", "of odc reduces synthesis of", "odc reduces synthesis of polyamines.", "of polyamines. additionally", "additionally antizyme also inhibits", "antizyme also inhibits polyamine transport", "also inhibits polyamine transport into", "inhibits polyamine transport into the", "polyamine transport into the cell.", "transport into the cell. antizyme", "into the cell. antizyme production", "the cell. antizyme production is", "cell. antizyme production is reduced", "production is reduced completing", "is reduced completing the", "reduced completing the regulatory", "the regulatory circuit coffino", "circuit coffino 2001", "coffino 2001 .
the following", "2001 .
the following illustration is", ".
the following illustration is adapted", "following illustration is adapted from", "illustration is adapted from a", "is adapted from a minireview", "adapted from a minireview by", "from a minireview by pegg", "minireview by pegg 2006", "pegg 2006 j.", "2006 j. biol. chem.", "j. biol. chem. vol.", "biol. chem. vol. 281", "vol. 281 issue 21", "issue 21 14529 14532." ] }, { "record_id": "GLY_000594_1_279", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3560783", "r hsa", "hsa 3560783", "r hsa 3560783" ] }, { "record_id": "GLY_000594_1_279", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective b4galt7", "b4galt7 causes", "causes eds", "progeroid type", "defective b4galt7 causes", "b4galt7 causes eds", "eds progeroid", "defective b4galt7 causes eds", "causes eds progeroid", "eds progeroid type", "b4galt7 causes eds progeroid", "causes eds progeroid type", "ehlers\u2013danlos syndrome", "is a", 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"more elastic. the", "elastic. the severity", "the severity of", "severity of the", "of the mutation", "the mutation can", "mutation can vary", "can vary from", "vary from mild", "from mild to", "mild to life", "to life threatening.", "life threatening. there", "threatening. there is", "there is no", "is no cure", "no cure and", "cure and treatment", "and treatment is", "treatment is supportive", "supportive including", "including close monitoring", "close monitoring of", "monitoring of the", "of the digestive", "digestive excretory", "excretory and particularly", "and particularly the", "particularly the cardiovascular", "the cardiovascular systems.", "cardiovascular systems. defective", "systems. defective b4galt7", "b4galt7 a", "a galactosyltransferase important", "galactosyltransferase important in", "important in proteoglycan", "in proteoglycan synthesis", "synthesis causes", "causes the progeroid", "the progeroid variant", "progeroid variant of", "variant of eds", "eds 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"tissues more elastic. the severity", "more elastic. the severity of", "elastic. the severity of the", "the severity of the mutation", "severity of the mutation can", "of the mutation can vary", "the mutation can vary from", "mutation can vary from mild", "can vary from mild to", "vary from mild to life", "from mild to life threatening.", "mild to life threatening. there", "to life threatening. there is", "life threatening. there is no", "threatening. there is no cure", "there is no cure and", "is no cure and treatment", "no cure and treatment is", "cure and treatment is supportive", "treatment is supportive including", "is supportive including close", "supportive including close monitoring", "including close monitoring of the", "close monitoring of the digestive", "of the digestive excretory", "the digestive excretory and", "digestive excretory and particularly", "excretory and particularly the cardiovascular", "and particularly the cardiovascular systems.", "particularly the 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l1cam members", "adhesion.
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regions of", "regions of l1cam", "of l1cam members", "l1cam members are", "members are divergent", "are divergent and", "divergent and differ", "and differ in", "differ in their", "in their abilities", "their abilities to", "abilities to interact", "to interact with", "interact with extracellular", "extracellular heterophilic", "heterophilic ligands. the", "ligands. the l1", "the l1 ligands", "l1 ligands include", "ligands include other", "include other ig", "other ig domain", "ig domain cams", "cams such", "such as ncam", "ncam tag", "tag 1/axonin and", "1/axonin and f11", "proteoglycans type molecules", "molecules neurocan", "integrins and", "and extra cellular", "extra cellular matrix", "cellular matrix protein", "matrix protein laminin", "laminin neuropilin", "1 fgf", "fgf and egf", "and egf receptors.", "egf receptors. some", "receptors. some of", "some of these", "of these l1", "these l1 interacting", "l1 interacting proteins", "interacting proteins also", "proteins also bind", "also bind to", "bind to other", "to other l1cam", "other l1cam members.", "l1cam members. for", "members. for example", "for example tag", "example tag 1/axonin", "tag 1/axonin interact", "1/axonin interact with", "interact with l1", "with l1 and", "l1 and nrcam", "nrcam l1", "l1 neurofascin", "neurofascin and chl1", "and chl1 binds", "chl1 binds to", "binds to contactin", "to contactin family", "contactin family members.", "family members. the", "members. the cytoplasmic", "the cytoplasmic domains", "cytoplasmic domains of", "domains of l1cam", "members are most", "are most highly", "most highly conserved.", "highly conserved. nevertheless", "nevertheless they", "they have different", "have different cytoplasmic", "different cytoplasmic binding", "cytoplasmic binding partners", "partners and", "and even those", "even those with", "those with similar", "with similar binding", "similar binding partners", "binding partners may", "partners may be", "may be involved", "be involved in", "involved in different", "in different signaling", "different signaling complexes", "signaling complexes and", "complexes and mechanisms.", "and mechanisms. the", "mechanisms. the most", "the most conserved", "most conserved feature", "conserved feature of", "feature of l1cams", "of l1cams is", "l1cams is their", "is their ability", "their ability to", "ability to interact", "interact with the", "with the actin", "the actin cytoskeletal", "actin cytoskeletal adapter", "cytoskeletal adapter protein", "adapter protein ankyrin.", "protein ankyrin. the", "ankyrin. the cytoplasmic", "the cytoplasmic ankyrin", "cytoplasmic ankyrin binding", "ankyrin binding domain", "domain exhibits", "exhibits the highest", "the highest degree", "highest degree of", "degree of amino", "of amino acid", "amino acid conservation", "acid conservation throughout", "conservation throughout the", "throughout the l1", "the l1 family.", "the l1 family of", "l1 family of cell", "family of cell adhesion", "of cell adhesion molecules", "adhesion molecules l1cams", "l1cams are a", "are a subfamily of", "a subfamily of the", "subfamily of the immunoglobulin", "of the immunoglobulin superfamily", "the immunoglobulin superfamily of", "immunoglobulin superfamily of transmembrane", "superfamily of transmembrane receptors", "transmembrane receptors comprised", "receptors comprised of", "comprised of four structurally", "of four structurally related", "four structurally related proteins:", "structurally related proteins: l1", "proteins: l1 close", "l1 close homolog", "close homolog of l1", "of l1 chl1", "chl1 nrcam", "nrcam and neurofascin.", "and neurofascin. these cams", "neurofascin. these cams contain", "these cams contain six", "cams contain six ig", "contain six ig like", "six ig like domains", "like domains five", "domains five or", "five or six fibronectin", "or six fibronectin like", "six fibronectin like repeats", "like repeats a", "repeats a transmembrane", "a transmembrane region and", "transmembrane region and a", "region and a cytoplasmic", "and a cytoplasmic domain.", "a cytoplasmic domain. the", "cytoplasmic domain. the l1cam", "domain. the l1cam family", "the l1cam family has", "l1cam family has been", "family has been implicated", "has been implicated in", "been implicated in processes", "implicated in processes integral", "in processes integral to", "processes integral to nervous", "integral to nervous system", "to nervous system development", "system development including", "development including neurite", "neurite outgrowth neurite", "outgrowth neurite fasciculation", "neurite fasciculation and inter", "fasciculation and inter neuronal", "and inter neuronal adhesion.
l1cam", "inter neuronal adhesion.
l1cam members", "neuronal adhesion.
l1cam members are", "adhesion.
l1cam members are predominately", "members are predominately expressed", "are predominately expressed by", "predominately expressed by neuronal", "by neuronal as", "neuronal as well", "as well as some", "well as some nonneuronal", "as some nonneuronal cells", "nonneuronal cells during", "cells during development.", "during development. except", "development. except chl1", "except chl1 all the", "chl1 all the other", "all the other members", "the other members of", "other members of l1", "members of l1 family", "of l1 family contain", "l1 family contain an", "family contain an alternatively", "contain an alternatively spliced", "an alternatively spliced 12", "alternatively spliced 12 nclueotide", "spliced 12 nclueotide exon", "nclueotide exon encoding", "exon encoding the", "encoding the amino acid", "the amino acid residues", "amino acid residues rsle", "acid residues rsle in", "residues rsle in the", "rsle in the neuronal", "in the neuronal splice", "the neuronal splice forms", "neuronal splice forms but", "splice forms but missing", "forms but missing in", "but missing in the", "missing in the non", "in the non neuronal", "the non neuronal cells.", "non neuronal cells. the", "neuronal cells. the extracellular", "cells. the extracellular regions", "the extracellular regions of", "extracellular regions of l1cam", "regions of l1cam members", "of l1cam members are", "l1cam members are divergent", "members are divergent and", "are divergent and differ", "divergent and differ in", "and differ in their", "differ in their abilities", "in their abilities to", "their abilities to interact", "abilities to interact with", "to interact with extracellular", "with extracellular heterophilic", "extracellular heterophilic ligands.", "heterophilic ligands. the l1", "ligands. the l1 ligands", "the l1 ligands include", "l1 ligands include other", "ligands include other ig", "include other ig domain", "other ig domain cams", "domain cams such", "cams such as", "as ncam tag", "ncam tag 1/axonin", "tag 1/axonin and f11", "f11 proteoglycans", "type molecules neurocan", "neurocan beta1", "beta1 integrins and", "integrins and extra", "and extra cellular matrix", "extra cellular matrix protein", "cellular matrix protein laminin", "protein laminin neuropilin", "laminin neuropilin 1", "neuropilin 1 fgf", "1 fgf and", "fgf and egf receptors.", "and egf receptors. some", "egf receptors. some of", "receptors. some of these", "some of these l1", "of these l1 interacting", "these l1 interacting proteins", "l1 interacting proteins also", "interacting proteins also bind", "proteins also bind to", "also bind to other", "bind to other l1cam", "to other l1cam members.", "other l1cam members. for", "l1cam members. for example", "members. for example tag", "for example tag 1/axonin", "example tag 1/axonin interact", "tag 1/axonin interact with", "1/axonin interact with l1", "interact with l1 and", "with l1 and nrcam", "and nrcam l1", "l1 neurofascin and", "neurofascin and chl1 binds", "and chl1 binds to", "chl1 binds to contactin", "binds to contactin family", "to contactin family members.", "contactin family members. the", "family members. the cytoplasmic", "members. the cytoplasmic domains", "the cytoplasmic domains of", "cytoplasmic domains of l1cam", "domains of l1cam members", "l1cam members are most", "members are most highly", "are most highly conserved.", "most highly conserved. nevertheless", "conserved. nevertheless they", "nevertheless they have", "they have different cytoplasmic", "have different cytoplasmic binding", "different cytoplasmic binding partners", "binding partners and", "partners and even", "and even those with", "even those with similar", "those with similar binding", "with similar binding partners", "similar binding partners may", "binding partners may be", "partners may be involved", "may be involved in", "be involved in different", "involved in different signaling", "in different signaling complexes", "different signaling complexes and", "signaling complexes and mechanisms.", "complexes and mechanisms. the", "and mechanisms. the most", "mechanisms. the most conserved", "the most conserved feature", "most conserved feature of", "conserved feature of l1cams", "feature of l1cams is", "of l1cams is their", "l1cams is their ability", "is their ability to", "their ability to interact", "ability to interact with", "to interact with the", "interact with the actin", "with the actin cytoskeletal", "the actin cytoskeletal adapter", "actin cytoskeletal adapter protein", "cytoskeletal adapter protein ankyrin.", "adapter protein ankyrin. the", "protein ankyrin. the cytoplasmic", "ankyrin. the cytoplasmic ankyrin", "the cytoplasmic ankyrin binding", "cytoplasmic ankyrin binding domain", "binding domain exhibits", "domain exhibits the", "exhibits the highest degree", "the highest degree of", "highest degree of amino", "degree of amino acid", "of amino acid conservation", "amino acid conservation throughout", "acid conservation throughout the", "conservation throughout the l1", "throughout the l1 family.", "the l1 family of cell", "l1 family of cell adhesion", "family of cell adhesion molecules", "cell adhesion molecules l1cams", "molecules l1cams are", "l1cams are a subfamily", "are a subfamily of the", "a subfamily of the immunoglobulin", "subfamily of the immunoglobulin superfamily", "of the immunoglobulin superfamily of", "the immunoglobulin superfamily of transmembrane", "immunoglobulin superfamily of transmembrane receptors", "of transmembrane receptors comprised", "transmembrane receptors comprised of", "receptors comprised of four", "comprised of four structurally related", "of four structurally related proteins:", "four structurally related proteins: l1", "related proteins: l1 close", "proteins: l1 close homolog", "l1 close homolog of", "homolog of l1 chl1", "nrcam and neurofascin. these", "and neurofascin. these cams contain", "neurofascin. these cams contain six", "these cams contain six ig", "cams contain six ig like", "contain six ig like domains", "ig like domains five", "like domains five or", "domains five or six", "five or six fibronectin like", "or six fibronectin like repeats", "fibronectin like repeats a", "like repeats a transmembrane", "repeats a transmembrane region", "a transmembrane region and a", "transmembrane region and a cytoplasmic", "region and a cytoplasmic domain.", "and a cytoplasmic domain. the", "a cytoplasmic domain. the l1cam", "cytoplasmic domain. the l1cam family", "domain. the l1cam family has", "the l1cam family has been", "l1cam family has been implicated", "family has been implicated in", "has been implicated in processes", "been implicated in processes integral", "implicated in processes integral to", "in processes integral to nervous", "processes integral to nervous system", "integral to nervous system development", "nervous system development including", "system development including neurite", "development including neurite outgrowth", "including neurite outgrowth neurite", "neurite outgrowth neurite fasciculation", "outgrowth neurite fasciculation and", "neurite fasciculation and inter neuronal", "fasciculation and inter neuronal adhesion.
l1cam", "and inter neuronal adhesion.
l1cam members", "inter neuronal adhesion.
l1cam members are", "neuronal adhesion.
l1cam members are predominately", "adhesion.
l1cam members are predominately expressed", "members are predominately expressed by", "are predominately expressed by neuronal", "expressed by neuronal as", "by neuronal as well", "neuronal as well as", "as well as some nonneuronal", "well as some nonneuronal cells", "some nonneuronal cells during", "nonneuronal cells during development.", "during development. except chl1", "development. except chl1 all", "except chl1 all the other", "chl1 all the other members", "all the other members of", "the other members of l1", "other members of l1 family", "members of l1 family contain", "of l1 family contain an", "l1 family contain an alternatively", "family contain an alternatively spliced", "contain an alternatively spliced 12", "an alternatively spliced 12 nclueotide", "alternatively spliced 12 nclueotide exon", "12 nclueotide exon encoding", "nclueotide exon encoding the", "exon encoding the amino", "encoding the amino acid residues", "the amino acid residues rsle", "amino acid residues rsle in", "acid residues rsle in the", "residues rsle in the neuronal", "rsle in the neuronal splice", "in the neuronal splice forms", "the neuronal splice forms but", "neuronal splice forms but missing", "splice forms but missing in", "forms but missing in the", "but missing in the non", "missing in the non neuronal", "in the non neuronal cells.", "the non neuronal cells. the", "non neuronal cells. the extracellular", "neuronal cells. the extracellular regions", "cells. the extracellular regions of", "the extracellular regions of l1cam", "extracellular regions of l1cam members", "regions of l1cam members are", "of l1cam members are divergent", "l1cam members are divergent and", "members are divergent and differ", "are divergent and differ in", "divergent and differ in their", "and differ in their abilities", "differ in their abilities to", "in their abilities to interact", "their abilities to interact with", "abilities to interact with extracellular", "interact with extracellular heterophilic", "with extracellular heterophilic ligands.", "extracellular heterophilic ligands. the", "heterophilic ligands. the l1 ligands", "ligands. the l1 ligands include", "the l1 ligands include other", "l1 ligands include other ig", "ligands include other ig domain", "include other ig domain cams", "ig domain cams such", "domain cams such as", "cams such as ncam", "such as ncam tag", "as ncam tag 1/axonin", "ncam tag 1/axonin and", "and f11 proteoglycans", "f11 proteoglycans type", "proteoglycans type molecules neurocan", "neurocan beta1 integrins", "beta1 integrins and extra", "integrins and extra cellular", "and extra cellular matrix protein", "extra cellular matrix protein laminin", "matrix protein laminin neuropilin", "protein laminin neuropilin 1", "neuropilin 1 fgf and", "1 fgf and egf", "fgf and egf receptors. some", "and egf receptors. some of", "egf receptors. some of these", "receptors. some of these l1", "some of these l1 interacting", "of these l1 interacting proteins", "these l1 interacting proteins also", "l1 interacting proteins also bind", "interacting proteins also bind to", "proteins also bind to other", "also bind to other l1cam", "bind to other l1cam members.", "to other l1cam members. for", "other l1cam members. for example", "l1cam members. for example tag", "members. for example tag 1/axonin", "for example tag 1/axonin interact", "example tag 1/axonin interact with", "tag 1/axonin interact with l1", "1/axonin interact with l1 and", "interact with l1 and nrcam", "l1 and nrcam l1", "nrcam l1 neurofascin", "l1 neurofascin and chl1", "neurofascin and chl1 binds to", "and chl1 binds to contactin", "chl1 binds to contactin family", "binds to contactin family members.", "to contactin family members. the", "contactin family members. the cytoplasmic", "family members. the cytoplasmic domains", "members. the cytoplasmic domains of", "the cytoplasmic domains of l1cam", "cytoplasmic domains of l1cam members", "domains of l1cam members are", "of l1cam members are most", "l1cam members are most highly", "members are most highly conserved.", "are most highly conserved. nevertheless", "highly conserved. nevertheless they", "conserved. nevertheless they have", "nevertheless they have different", "they have different cytoplasmic binding", "have different cytoplasmic binding partners", "cytoplasmic binding partners and", "binding partners and even", "partners and even those", "and even those with similar", "even those with similar binding", "those with similar binding partners", "with similar binding partners may", "similar binding partners may be", "binding partners may be involved", "partners may be involved in", "may be involved in different", "be involved in different signaling", "involved in different signaling complexes", "in different signaling complexes and", "different signaling complexes and mechanisms.", "signaling complexes and mechanisms. the", "complexes and mechanisms. the most", "and mechanisms. the most conserved", "mechanisms. the most conserved feature", "the most conserved feature of", "most conserved feature of l1cams", "conserved feature of l1cams is", "feature of l1cams is their", "of l1cams is their ability", "l1cams is their ability to", "is their ability to interact", "their ability to interact with", "ability to interact with the", "to interact with the actin", "interact with the actin cytoskeletal", "with the actin cytoskeletal adapter", "the actin cytoskeletal adapter protein", "actin cytoskeletal adapter protein ankyrin.", "cytoskeletal adapter protein ankyrin. the", "adapter protein ankyrin. the cytoplasmic", "protein ankyrin. the cytoplasmic ankyrin", "ankyrin. the cytoplasmic ankyrin binding", "the cytoplasmic ankyrin binding domain", "ankyrin binding domain exhibits", "binding domain exhibits the", "domain exhibits the highest", "exhibits the highest degree of", "the highest degree of amino", "highest degree of amino acid", "degree of amino acid conservation", "of amino acid conservation throughout", "amino acid conservation throughout the", "acid conservation throughout the l1", "conservation throughout the l1 family." ] }, { "record_id": "GLY_000594_1_289", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "375165", "r hsa", "hsa 375165", "r hsa 375165" ] }, { "record_id": "GLY_000594_1_289", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ncam signaling", "signaling for", "for neurite", "neurite out", "out growth", "ncam signaling for", "signaling for neurite", "for neurite out", "neurite out growth", "ncam signaling for neurite", "signaling for neurite out", "for neurite out growth", "ncam signaling for neurite out", "signaling for neurite out growth", "the neural", "neural cell", "cell adhesion", "adhesion molecule", "is a", "a member", "member of", "of the", "the immunoglobulin", "superfamily and", "and is", "is involved", "involved in", "in a", "a variety", "variety of", "of cellular", "cellular processes", "processes of", "of importance", "importance for", "for the", "the formation", "formation and", "and maintenance", "maintenance of", "the nervous", "nervous system.", "system. the", "the role", "role of", "of ncam", "ncam in", "in neural", "neural differentiation", "differentiation and", "and synaptic", "synaptic plasticity", "plasticity is", "is presumed", "presumed to", "to depend", "depend on", "on the", "the modulation", "modulation of", "of intracellular", "intracellular signal", "signal transduction", "transduction cascades.", "cascades. ncam", "ncam based", "based signaling", "signaling complexes", "complexes can", "can initiate", "initiate downstream", "downstream intracellular", "intracellular signals", "signals by", "by at", "at least", "least two", "two mechanisms:", "activation of", "of fgfr", "fgfr and", "formation of", "intracellular signaling", "complexes by", "by direct", "direct interaction", "interaction with", "with cytoplasmic", "cytoplasmic interaction", "interaction partners", "partners such", "such as", "as fyn", "fyn and", "and fak.", "fak. tyrosine", "tyrosine kinases", "kinases fyn", "and fak", "fak interact", "interact with", "with ncam", "ncam and", "and undergo", "undergo phosphorylation", "phosphorylation and", "and this", "this transiently", "transiently activates", "activates the", "the mapk", "erk 1", "1 and", "and 2", "camp response", "response element", "element binding", "binding protein", "and transcription", "transcription factors", "factors elk", "elk and", "and nfkb.", "nfkb. creb", "creb activates", "activates transcription", "transcription of", "of genes", "genes which", "which are", "are important", "important for", "for axonal", "axonal growth", "plasticity in", "in neurons.

ncam1", "neurons.

ncam1 mediated", "mediated intracellular", "transduction is", "is represented", "represented in", "in the", "the figure", "figure below.", "below. the", "the ig", "ig domains", "domains in", "in ncam1", "ncam1 are", "are represented", "in orange", "orange ovals", "ovals and", "and fn", "fn domains", "in green", "green squares.", "squares. the", "the tyrosine", "tyrosine residues", "residues susceptible", "susceptible to", "to phosphorylation", "phosphorylation are", "in red", "red circles", "circles and", "and their", "their positions", "positions are", "are numbered.", "numbered. phosphorylation", "phosphorylation is", "represented by", "by red", "red arrows", "arrows and", "and dephosphorylation", "dephosphorylation by", "by yellow.", "yellow. ig", "immunoglobulin domain", "fibronectin domain", "proto oncogene", "oncogene tyrosine", "tyrosine protein", "protein kinase", "kinase fyn", "focal adhesion", "adhesion kinase", "receptor type", "type tyrosine", "protein phosphatase", "growth factor", "factor receptor", "receptor bound", "bound protein", "protein 2", "son of", "of sevenless", "sevenless homolog", "raf proto", "oncogene serine/threonine", "serine/threonine protein", "mapk and", "and erk", "erk kinase", "extracellular signal", "signal regulated", "regulated kinase", "mitogen and", "and stress", "stress activated", "activated protein", "kinase 1", "cyclic amp", "amp responsive", "responsive element", "response elements.", "the neural cell", "neural cell adhesion", "cell adhesion molecule", "molecule ncam", "ncam is", "is a member", "a member of", "member of the", "of the immunoglobulin", "immunoglobulin ig", "ig superfamily", "superfamily and is", "and is involved", "is involved in", "involved in a", "in a variety", "a variety of", "variety of cellular", "of cellular processes", "cellular processes of", "processes of importance", "of importance for", "importance for the", "for the formation", "the formation and", "formation and maintenance", "and maintenance of", "maintenance of the", "of the nervous", "the nervous system.", "nervous system. the", "system. the role", "the role of", "role of ncam", "of ncam in", "ncam in neural", "in neural differentiation", "neural differentiation and", "differentiation and synaptic", "and synaptic plasticity", "synaptic plasticity is", "plasticity is presumed", "is presumed to", "presumed to depend", "to depend on", "depend on the", "on the modulation", "the modulation of", "modulation of intracellular", "of intracellular signal", "intracellular signal transduction", "signal transduction cascades.", "transduction cascades. ncam", "cascades. ncam based", "ncam based signaling", "based signaling complexes", "signaling complexes can", "complexes can initiate", "can initiate downstream", "initiate downstream intracellular", "downstream intracellular signals", "intracellular signals by", "signals by at", "by at least", "at least two", "least two mechanisms:", "mechanisms: 1", "1 activation", "activation of fgfr", "of fgfr and", "2 formation", "formation of intracellular", "of intracellular signaling", "intracellular signaling complexes", "signaling complexes by", "complexes by direct", "by direct interaction", "direct interaction with", "interaction with cytoplasmic", "with cytoplasmic interaction", "cytoplasmic interaction partners", "interaction partners such", "partners such as", "such as fyn", "as fyn and", "fyn and fak.", "and fak. tyrosine", "fak. tyrosine kinases", "tyrosine kinases fyn", "kinases fyn and", "fyn and fak", "and fak interact", "fak interact with", "interact with ncam", "with ncam and", "ncam and undergo", "and undergo phosphorylation", "undergo phosphorylation and", "phosphorylation and this", "and this transiently", "this transiently activates", "transiently activates the", "activates the mapk", "mapk erk", "erk 1 and", "1 and 2", "2 camp", "camp response element", "response element binding", "element binding protein", "protein creb", "creb and", "and transcription factors", "transcription factors elk", "factors elk and", "elk and nfkb.", "and nfkb. creb", "nfkb. creb activates", "creb activates transcription", "activates transcription of", "transcription of genes", "of genes which", "genes which are", "which are important", "are important for", "important for axonal", "for axonal growth", "growth survival", "survival and", "synaptic plasticity in", "plasticity in neurons.

ncam1", "in neurons.

ncam1 mediated", "neurons.

ncam1 mediated intracellular", "mediated intracellular signal", "signal transduction is", "transduction is represented", "is represented in", "represented in the", "in the figure", "the figure below.", "figure below. the", "below. the ig", "the ig domains", "ig domains in", "domains in ncam1", "in ncam1 are", "ncam1 are represented", "are represented in", "represented in orange", "in orange ovals", "orange ovals and", "ovals and fn", "and fn domains", "fn domains in", "domains in green", "in green squares.", "green squares. the", "squares. the tyrosine", "the tyrosine residues", "tyrosine residues susceptible", "residues susceptible to", "susceptible to phosphorylation", "to phosphorylation are", "phosphorylation are represented", "represented in red", "in red circles", "red circles and", "circles and their", "and their positions", "their positions are", "positions are numbered.", "are numbered. phosphorylation", "numbered. phosphorylation is", "phosphorylation is represented", "is represented by", "represented by red", "by red arrows", "red arrows and", "arrows and dephosphorylation", "and dephosphorylation by", "dephosphorylation by yellow.", "by yellow. ig", "ig immunoglobulin", "domain fn", "fn fibronectin", "domain fyn", "fyn proto", "proto oncogene tyrosine", "oncogene tyrosine protein", "tyrosine protein kinase", "protein kinase fyn", "fyn fak", "fak focal", "focal adhesion kinase", "kinase rptpalpha", "rptpalpha receptor", "receptor type tyrosine", "type tyrosine protein", "tyrosine protein phosphatase", "phosphatase grb2", "grb2 growth", "growth factor receptor", "factor receptor bound", "receptor bound protein", "bound protein 2", "2 sos", "sos son", "son of sevenless", "of sevenless homolog", "homolog raf", "raf raf", "raf proto oncogene", "proto oncogene serine/threonine", "oncogene serine/threonine protein", "serine/threonine protein kinase", "kinase mek", "mek mapk", "mapk and erk", "and erk kinase", "kinase erk", "erk extracellular", "extracellular signal regulated", "signal regulated kinase", "kinase msk1", "msk1 mitogen", "mitogen and stress", "and stress activated", "stress activated protein", "activated protein kinase", "protein kinase 1", "1 creb", "creb cyclic", "cyclic amp responsive", "amp responsive element", "responsive element binding", "protein cre", "cre camp", "camp response elements.", "the neural cell adhesion", "neural cell adhesion molecule", "adhesion molecule ncam", "ncam is a", "is a member of", "a member of the", "member of the immunoglobulin", "the immunoglobulin ig", "ig superfamily and", "superfamily and is involved", "and is involved in", "is involved in a", "involved in a variety", "in a variety of", "a variety of cellular", "variety of cellular processes", "of cellular processes of", "cellular processes of importance", "processes of importance for", "of importance for the", "importance for the formation", "for the formation and", "the formation and maintenance", "formation and maintenance of", "and maintenance of the", "maintenance of the nervous", "of the nervous system.", "the nervous system. the", "nervous system. the role", "system. the role of", "the role of ncam", "role of ncam in", "of ncam in neural", "ncam in neural differentiation", "in neural differentiation and", "neural differentiation and synaptic", "differentiation and synaptic plasticity", "and synaptic plasticity is", "synaptic plasticity is presumed", "plasticity is presumed to", "is presumed to depend", "presumed to depend on", "to depend on the", "depend on the modulation", "on the modulation of", "the modulation of intracellular", "modulation of intracellular signal", "of intracellular signal transduction", "intracellular signal transduction cascades.", "signal transduction cascades. ncam", "transduction cascades. ncam based", "cascades. ncam based signaling", "ncam based signaling complexes", "based signaling complexes can", "signaling complexes can initiate", "complexes can initiate downstream", "can initiate downstream intracellular", "initiate downstream intracellular signals", "downstream intracellular signals by", "intracellular signals by at", "signals by at least", "by at least two", "at least two mechanisms:", "two mechanisms: 1", "1 activation of", "activation of fgfr and", "fgfr and 2", "2 formation of", "formation of intracellular signaling", "of intracellular signaling complexes", "intracellular signaling complexes by", "signaling complexes by direct", "complexes by direct interaction", "by direct interaction with", "direct interaction with cytoplasmic", "interaction with cytoplasmic interaction", "with cytoplasmic interaction partners", "cytoplasmic interaction partners such", "interaction partners such as", "partners such as fyn", "such as fyn and", "as fyn and fak.", "fyn and fak. tyrosine", "and fak. tyrosine kinases", "fak. tyrosine kinases fyn", "tyrosine kinases fyn and", "kinases fyn and fak", "fyn and fak interact", "and fak interact with", "fak interact with ncam", "interact with ncam and", "with ncam and undergo", "ncam and undergo phosphorylation", "and undergo phosphorylation and", "undergo phosphorylation and this", "phosphorylation and this transiently", "and this transiently activates", "this transiently activates the", "transiently activates the mapk", "the mapk erk", "mapk erk 1", "erk 1 and 2", "and 2 camp", "2 camp response", "camp response element binding", "response element binding protein", "binding protein creb", "creb and transcription", "and transcription factors elk", "transcription factors elk and", "factors elk and nfkb.", "elk and nfkb. creb", "and nfkb. creb activates", "nfkb. creb activates transcription", "creb activates transcription of", "activates transcription of genes", "transcription of genes which", "of genes which are", "genes which are important", "which are important for", "are important for axonal", "important for axonal growth", "axonal growth survival", "survival and synaptic", "and synaptic plasticity in", "synaptic plasticity in neurons.

ncam1", "plasticity in neurons.

ncam1 mediated", "in neurons.

ncam1 mediated intracellular", "neurons.

ncam1 mediated intracellular signal", "mediated intracellular signal transduction", "intracellular signal transduction is", "signal transduction is represented", "transduction is represented in", "is represented in the", "represented in the figure", "in the figure below.", "the figure below. the", "figure below. the ig", "below. the ig domains", "the ig domains in", "ig domains in ncam1", "domains in ncam1 are", "in ncam1 are represented", "ncam1 are represented in", "are represented in orange", "represented in orange ovals", "in orange ovals and", "orange ovals and fn", "ovals and fn domains", "and fn domains in", "fn domains in green", "domains in green squares.", "in green squares. the", "green squares. the tyrosine", "squares. the tyrosine residues", "the tyrosine residues susceptible", "tyrosine residues susceptible to", "residues susceptible to phosphorylation", "susceptible to phosphorylation are", "to phosphorylation are represented", "phosphorylation are represented in", "are represented in red", "represented in red circles", "in red circles and", "red circles and their", "circles and their positions", "and their positions are", "their positions are numbered.", "positions are numbered. phosphorylation", "are numbered. phosphorylation is", "numbered. phosphorylation is represented", "phosphorylation is represented by", "is represented by red", "represented by red arrows", "by red arrows and", "red arrows and dephosphorylation", "arrows and dephosphorylation by", "and dephosphorylation by yellow.", "dephosphorylation by yellow. ig", "yellow. ig immunoglobulin", "ig immunoglobulin domain", "immunoglobulin domain fn", "fn fibronectin domain", "fibronectin domain fyn", "fyn proto oncogene", "proto oncogene tyrosine protein", "oncogene tyrosine protein kinase", "tyrosine protein kinase fyn", "kinase fyn fak", "fak focal adhesion", "adhesion kinase rptpalpha", "rptpalpha receptor type", "receptor type tyrosine protein", "type tyrosine protein phosphatase", "protein phosphatase grb2", "grb2 growth factor", "growth factor receptor bound", "factor receptor bound protein", "receptor bound protein 2", "protein 2 sos", "sos son of", "son of sevenless homolog", "sevenless homolog raf", "raf raf proto", "raf proto oncogene serine/threonine", "proto oncogene serine/threonine protein", "oncogene serine/threonine protein kinase", "protein kinase mek", "mek mapk and", "mapk and erk kinase", "erk kinase erk", "erk extracellular signal", "extracellular signal regulated kinase", "regulated kinase msk1", "msk1 mitogen and", "mitogen and stress activated", "and stress activated protein", "stress activated protein kinase", "activated protein kinase 1", "kinase 1 creb", "creb cyclic amp", "cyclic amp responsive element", "amp responsive element binding", "responsive element binding protein", "binding protein cre", "cre camp response", "the neural cell adhesion molecule", "cell adhesion molecule ncam", "molecule ncam is", "ncam is a member", "is a member of the", "a member of the immunoglobulin", "of the immunoglobulin ig", "immunoglobulin ig superfamily", "ig superfamily and is", "superfamily and is involved in", "and is involved in a", "is involved in a variety", "involved in a variety of", "in a variety of cellular", "a variety of cellular processes", "variety of cellular processes of", "of cellular processes of importance", "cellular processes of importance for", "processes of importance for the", "of importance for the formation", "importance for the formation and", "for the formation and maintenance", "the formation and maintenance of", "formation and maintenance of the", "and maintenance of the nervous", "maintenance of the nervous system.", "of the nervous system. the", "the nervous system. the role", "nervous system. the role of", "system. the role of ncam", "the role of ncam in", "role of ncam in neural", "of ncam in neural differentiation", "ncam in neural differentiation and", "in neural differentiation and synaptic", "neural differentiation and synaptic plasticity", "differentiation and synaptic plasticity is", "and synaptic plasticity is presumed", "synaptic plasticity is presumed to", "plasticity is presumed to depend", "is presumed to depend on", "presumed to depend on the", "to depend on the modulation", "depend on the modulation of", "on the modulation of intracellular", "the modulation of intracellular signal", "modulation of intracellular signal transduction", "of intracellular signal transduction cascades.", "intracellular signal transduction cascades. ncam", "signal transduction cascades. ncam based", "transduction cascades. ncam based signaling", "cascades. ncam based signaling complexes", "ncam based signaling complexes can", "based signaling complexes can initiate", "signaling complexes can initiate downstream", "complexes can initiate downstream intracellular", "can initiate downstream intracellular signals", "initiate downstream intracellular signals by", "downstream intracellular signals by at", "intracellular signals by at least", "signals by at least two", "by at least two mechanisms:", "least two mechanisms: 1", "mechanisms: 1 activation", "1 activation of fgfr", "of fgfr and 2", "and 2 formation", "2 formation of intracellular", "formation of intracellular signaling complexes", "of intracellular signaling complexes by", "intracellular signaling complexes by direct", "signaling complexes by direct interaction", "complexes by direct interaction with", "by direct interaction with cytoplasmic", "direct interaction with cytoplasmic interaction", "interaction with cytoplasmic interaction partners", "with cytoplasmic interaction partners such", "cytoplasmic interaction partners such as", "interaction partners such as fyn", "partners such as fyn and", "such as fyn and fak.", "as fyn and fak. tyrosine", "fyn and fak. tyrosine kinases", "and fak. tyrosine kinases fyn", "fak. tyrosine kinases fyn and", "tyrosine kinases fyn and fak", "kinases fyn and fak interact", "fyn and fak interact with", "and fak interact with ncam", "fak interact with ncam and", "interact with ncam and undergo", "with ncam and undergo phosphorylation", "ncam and undergo phosphorylation and", "and undergo phosphorylation and this", "undergo phosphorylation and this transiently", "phosphorylation and this transiently activates", "and this transiently activates the", "this transiently activates the mapk", "activates the mapk erk", "the mapk erk 1", "mapk erk 1 and", "1 and 2 camp", "and 2 camp response", "2 camp response element", "camp response element binding protein", "element binding protein creb", "protein creb and", "creb and transcription factors", "and transcription factors elk and", "transcription factors elk and nfkb.", "factors elk and nfkb. creb", "elk and nfkb. creb activates", "and nfkb. creb activates transcription", "nfkb. creb activates transcription of", "creb activates transcription of genes", "activates transcription of genes which", "transcription of genes which are", "of genes which are important", "genes which are important for", "which are important for axonal", "are important for axonal growth", "for axonal growth survival", "growth survival and", "survival and synaptic plasticity", "and synaptic plasticity in neurons.

ncam1", "synaptic plasticity in neurons.

ncam1 mediated", "plasticity in neurons.

ncam1 mediated intracellular", "in neurons.

ncam1 mediated intracellular signal", "neurons.

ncam1 mediated intracellular signal transduction", "mediated intracellular signal transduction is", "intracellular signal transduction is represented", "signal transduction is represented in", "transduction is represented in the", "is represented in the figure", "represented in the figure below.", "in the figure below. the", "the figure below. the ig", "figure below. the ig domains", "below. the ig domains in", "the ig domains in ncam1", "ig domains in ncam1 are", "domains in ncam1 are represented", "in ncam1 are represented in", "ncam1 are represented in orange", "are represented in orange ovals", "represented in orange ovals and", "in orange ovals and fn", "orange ovals and fn domains", "ovals and fn domains in", "and fn domains in green", "fn domains in green squares.", "domains in green squares. the", "in green squares. the tyrosine", "green squares. the tyrosine residues", "squares. the tyrosine residues susceptible", "the tyrosine residues susceptible to", "tyrosine residues susceptible to phosphorylation", "residues susceptible to phosphorylation are", "susceptible to phosphorylation are represented", "to phosphorylation are represented in", "phosphorylation are represented in red", "are represented in red circles", "represented in red circles and", "in red circles and their", "red circles and their positions", "circles and their positions are", "and their positions are numbered.", "their positions are numbered. phosphorylation", "positions are numbered. phosphorylation is", "are numbered. phosphorylation is represented", "numbered. phosphorylation is represented by", "phosphorylation is represented by red", "is represented by red arrows", "represented by red arrows and", "by red arrows and dephosphorylation", "red arrows and dephosphorylation by", "arrows and dephosphorylation by yellow.", "and dephosphorylation by yellow. ig", "by yellow. ig immunoglobulin", "yellow. ig immunoglobulin domain", "domain fn fibronectin", "domain fyn proto", "fyn proto oncogene tyrosine", "proto oncogene tyrosine protein kinase", "oncogene tyrosine protein kinase fyn", "protein kinase fyn fak", "fyn fak focal", "fak focal adhesion kinase", "focal adhesion kinase rptpalpha", "kinase rptpalpha receptor", "rptpalpha receptor type tyrosine", "receptor type tyrosine protein phosphatase", "tyrosine protein phosphatase grb2", "phosphatase grb2 growth", "grb2 growth factor receptor", "growth factor receptor bound protein", "factor receptor bound protein 2", "bound protein 2 sos", "2 sos son", "sos son of sevenless", "of sevenless homolog raf", "homolog raf raf", "raf raf proto oncogene", "raf proto oncogene serine/threonine protein", "proto oncogene serine/threonine protein kinase", "serine/threonine protein kinase mek", "kinase mek mapk", "mek mapk and erk", "and erk kinase erk", "kinase erk extracellular", "erk extracellular signal regulated", "signal regulated kinase msk1", "kinase msk1 mitogen", "msk1 mitogen and stress", "mitogen and stress activated protein", "and stress activated protein kinase", "stress activated protein kinase 1", "protein kinase 1 creb", "1 creb cyclic", "creb cyclic amp responsive", "cyclic amp responsive element binding", "amp responsive element binding protein", "element binding protein cre", "protein cre camp", "cre camp response elements." ] }, { "record_id": "GLY_000594_1_290", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "375276", "r hsa", "hsa 375276", "r hsa 375276" ] }, { "record_id": "GLY_000594_1_290", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "peptide ligand", "ligand binding", "binding receptors", "peptide ligand binding", "ligand binding receptors", "peptide ligand binding receptors", "these receptors", "a subset", "subset of", "of the", "the class", "class a/1", "rhodopsin like", "all bind", "bind peptide", "peptide ligands", "ligands which", "which include", "include the", "the chemokines", "opioids and", "and somatostatins.", "receptors a", "a subset of", "subset of the", "of the class", "the class a/1", "a/1 rhodopsin", "like family", "family all", "all bind peptide", "bind peptide ligands", "peptide ligands which", "ligands which include", "which include the", "include the chemokines", "chemokines opioids", "opioids and somatostatins.", "these receptors a", "receptors a subset", "a subset of the", "subset of the class", "of the class a/1", "class a/1 rhodopsin", "a/1 rhodopsin like", "rhodopsin like family", "family all bind", "all bind peptide ligands", "bind peptide ligands which", "peptide ligands which include", "ligands which include the", "which include the chemokines", "the chemokines opioids", "chemokines opioids and", "these receptors a subset", "receptors a subset of", "a subset of the class", "subset of the class a/1", "the class a/1 rhodopsin", "class a/1 rhodopsin like", "like family all", "family all bind peptide", "all bind peptide ligands which", "bind peptide ligands which include", "peptide ligands which include the", "ligands which include the chemokines", "include the chemokines opioids", "the chemokines opioids and", "chemokines opioids and somatostatins." ] }, { "record_id": "GLY_000594_1_291", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "375280", "r hsa", "hsa 375280", "r hsa 375280" ] }, { "record_id": "GLY_000594_1_291", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "amine ligand", "ligand binding", "binding receptors", "amine ligand binding", "ligand binding receptors", "amine ligand binding receptors", "the class", "class a", "rhodopsin like", "gpcrs that", "that bind", "bind to", "to classical", "classical biogenic", "biogenic amine", "amine ligands", "ligands are", "are annotated", "annotated here.", "here. the", "the amines", "amines involved", "serotonin and", "and histamine", "can all", "all act", "act as", "as 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"GLY_000594_1_292", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "376172", "r hsa", "hsa 376172", "r hsa 376172" ] }, { "record_id": "GLY_000594_1_292", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dscam interactions", "down syndrome", "syndrome cell", "cell adhesion", "adhesion molecule", "is one", "one of", "of the", "the members", "members of", "the ig", "ig superfamily", "superfamily cams", "cams with", "with a", "a domain", "domain architecture", "architecture comprising", "comprising 10", "10 ig", "ig domains", "6 fibronectin", "fibronectin type", "type iii", "a single", "single transmembrane", "transmembrane and", "and a", "a c", "c terminal", "terminal cytoplasmic", "cytoplasmic domain.", "domain. dscam", "dscam is", "is implicated", "implicated in", "in down", "due to", "to the", "the chromosomal", "chromosomal location", "location of", "the dscam", "dscam gene", "but no", "no 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intercellular", "intercellular interactions.", "dscam down", "down syndrome cell", "syndrome cell adhesion", "cell adhesion molecule", "molecule is", "is one of", "one of the", "of the members", "the members of", "members of the", "of the ig", "the ig superfamily", "ig superfamily cams", "superfamily cams with", "cams with a", "with a domain", "a domain architecture", "domain architecture comprising", "architecture comprising 10", "comprising 10 ig", "10 ig domains", "domains 6", "6 fibronectin type", "fibronectin type iii", "iii fn", "fn repeats", "repeats a", "a single transmembrane", "single transmembrane and", "transmembrane and a", "and a c", "a c terminal", "c terminal cytoplasmic", "terminal cytoplasmic domain.", "cytoplasmic domain. dscam", "domain. dscam is", "dscam is implicated", "is implicated in", "implicated in down", "in down syndrome", "syndrome ds", "ds due", "due to the", "to the chromosomal", "the chromosomal location", "chromosomal location of", "location of the", "of the dscam", "the dscam gene", "gene but", "but no evidence", "no evidence supports", "evidence supports a", "supports a direct", "a direct involvement", "direct involvement of", "involvement of dscam", "of dscam with", "dscam with ds.", "with ds. it", "ds. it likely", "it likely functions", "likely functions as", "functions as a", "as a cell", "a cell surface", "cell surface receptor", "surface receptor mediating", "receptor mediating axon", "mediating axon pathfinding.", "axon pathfinding. besides", "pathfinding. besides these", "besides these important", "these important implications", "implications little", "little is known", "is known about", "known about the", "about the physiological", "the physiological function", "physiological function or", "function or the", "or the molecular", "the molecular mechanism", "molecular mechanism of", "mechanism of dscam", "of dscam signal", "dscam signal transduction", "signal transduction in", "transduction in mammalian", "in mammalian systems.", "mammalian systems. a", "systems. a closely", "a closely related", "closely related dscam", "related dscam paralogue", "dscam paralogue down", "paralogue down syndrome", "cell adhesion moleculelike", "adhesion moleculelike protein", "moleculelike protein 1", "1 dscaml1", "dscaml1 is", "is present in", "present in humans.", "in humans. both", "humans. both these", "both these proteins", "these proteins are", "proteins are involved", "are involved in", "involved in homophilic", "in homophilic intercellular", "homophilic intercellular interactions.", "dscam down syndrome", "down syndrome cell adhesion", "syndrome cell adhesion molecule", "adhesion molecule is", "molecule is one", "is one of the", "one of the members", "of the members of", "the members of the", "members of the ig", "of the ig superfamily", "the ig superfamily cams", "ig superfamily cams with", "superfamily cams with a", "cams with a domain", "with a domain architecture", "a domain architecture comprising", 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ds.", "dscam with ds. it", "with ds. it likely", "ds. it likely functions", "it likely functions as", "likely functions as a", "functions as a cell", "as a cell surface", "a cell surface receptor", "cell surface receptor mediating", "surface receptor mediating axon", "receptor mediating axon pathfinding.", "mediating axon pathfinding. besides", "axon pathfinding. besides these", "pathfinding. besides these important", "besides these important implications", "important implications little", "implications little is", "little is known about", "is known about the", "known about the physiological", "about the physiological function", "the physiological function or", "physiological function or the", "function or the molecular", "or the molecular mechanism", "the molecular mechanism of", "molecular mechanism of dscam", "mechanism of dscam signal", "of dscam signal transduction", "dscam signal transduction in", "signal transduction in mammalian", "transduction in mammalian systems.", "in mammalian systems. a", "mammalian systems. a closely", "systems. a closely related", "a closely related dscam", "closely related dscam paralogue", "related dscam paralogue down", "dscam paralogue down syndrome", "paralogue down syndrome cell", "syndrome cell adhesion moleculelike", "cell adhesion moleculelike protein", "adhesion moleculelike protein 1", "protein 1 dscaml1", "dscaml1 is present", "is present in humans.", "present in humans. both", "in humans. both these", "humans. both these proteins", "both these proteins are", "these proteins are involved", "proteins are involved in", "are involved in homophilic", "involved in homophilic intercellular", "in homophilic intercellular interactions.", "dscam down syndrome cell", "down syndrome cell adhesion molecule", "cell adhesion molecule is", "adhesion molecule is one", "molecule is one of", "is one of the members", "one of the members of", "of the members of the", "the members of the ig", "members of the ig superfamily", "of the ig superfamily cams", "the ig superfamily cams with", "ig superfamily cams with a", "superfamily cams with a domain", "cams with a domain architecture", "with a domain architecture comprising", "a domain architecture comprising 10", "domain architecture comprising 10 ig", "architecture comprising 10 ig domains", "10 ig domains 6", "ig domains 6 fibronectin", "domains 6 fibronectin type", "fibronectin type iii fn", "iii fn repeats", "fn repeats a", "repeats a single transmembrane", "a single transmembrane and a", "single transmembrane and a c", "transmembrane and a c terminal", "and a c terminal cytoplasmic", "a c terminal cytoplasmic domain.", "c terminal cytoplasmic domain. dscam", "terminal cytoplasmic domain. dscam is", "cytoplasmic domain. dscam is implicated", "domain. dscam is implicated in", "dscam is implicated in down", "is implicated in down syndrome", "in down syndrome ds", "syndrome ds due", "ds due to the", "due to the chromosomal location", "to the chromosomal location of", "the chromosomal location of the", "chromosomal location of the dscam", "location of the dscam gene", "the dscam gene but", "dscam gene but no", "gene but no evidence", "but no evidence supports a", "no evidence supports a direct", "evidence supports a direct involvement", "supports a direct involvement of", "a direct involvement of dscam", "direct involvement of dscam with", "involvement of dscam with ds.", "of dscam with ds. it", "dscam with ds. it likely", "with ds. it likely functions", "ds. it likely functions as", "it likely functions as a", "likely functions as a cell", "functions as a cell surface", "as a cell surface receptor", "a cell surface receptor mediating", "cell surface receptor mediating axon", "surface receptor mediating axon pathfinding.", "receptor mediating axon pathfinding. besides", "mediating axon pathfinding. besides these", "axon pathfinding. besides these important", "pathfinding. besides these important implications", "these important implications little", "important implications little is", "implications little is known", "little is known about the", "is known about the physiological", "known about the physiological function", "about the physiological function or", "the physiological function or the", "physiological function or the molecular", "function or the molecular mechanism", "or the molecular mechanism of", "the molecular mechanism of dscam", "molecular mechanism of dscam signal", "mechanism of dscam signal transduction", "of dscam signal transduction in", "dscam signal transduction in mammalian", "signal transduction in mammalian systems.", "transduction in mammalian systems. a", "in mammalian systems. a closely", "mammalian systems. a closely related", "systems. a closely related dscam", "a closely related dscam paralogue", "closely related dscam paralogue down", "related dscam paralogue down syndrome", "dscam paralogue down syndrome cell", "paralogue down syndrome cell adhesion", "down syndrome cell adhesion moleculelike", "syndrome cell adhesion moleculelike protein", "cell adhesion moleculelike protein 1", "moleculelike protein 1 dscaml1", "1 dscaml1 is", "dscaml1 is present in", "is present in humans. both", "present in humans. both these", "in humans. both these proteins", "humans. both these proteins are", "both these proteins are involved", "these proteins are involved in", "proteins are involved in homophilic", "are involved in homophilic intercellular", "involved in homophilic intercellular interactions." ] }, { "record_id": "GLY_000594_1_293", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "376176", "r hsa", "hsa 376176", "r hsa 376176" ] }, { "record_id": "GLY_000594_1_293", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by robo", "robo receptors", "signaling by robo", "by robo receptors", "signaling by robo receptors", "the roundabout", "family encodes", "encodes transmembrane", "transmembrane receptors", "receptors that", "that regulate", "regulate axonal", "axonal guidance", "guidance and", "and cell", "cell migration.", "migration. the", "the major", "major function", "function of", "of the", "the robo", "receptors is", "is to", "to mediate", "mediate repulsion", "repulsion of", "the navigating", "navigating growth", "growth cones.", "cones. there", "there are", "are four", "four human", "human robo", "robo homologues", "robo3 and", "and robo4.", "robo4. most", "most of", "the robos", "robos have", "have the", "the similar", "similar ectodomain", "ectodomain architecture", "architecture as", "as the", "the cell", "cell adhesion", "adhesion molecules", "with five", "five ig", "ig domains", "domains followed", "followed by", "by three", "three fn3", "fn3 repeats", "except for", "for robo4.", "robo4. robo4", "robo4 has", "has two", "two ig", "ig and", "and two", "two fn3", "fn3 repeats.", "repeats. the", "the cytoplasmic", "cytoplasmic domains", "domains of", "of robo", "receptors are", "are in", "in general", "general poorly", "poorly conserved.", "conserved. however", "four short", "short conserved", "conserved cytoplasmic", "cytoplasmic sequence", "sequence motifs", "named cc0", "cc0 3", "that serve", "serve as", "as binding", "binding sites", "sites for", "for adaptor", "adaptor proteins.", "proteins. the", "the ligands", "ligands for", "for the", "the human", "human robo1", "robo1 and", "and robo2", "robo2 receptors", "are the", "the three", "three slit", "slit proteins", "proteins slit1", "and slit3", "all of", "the slit", "proteins contain", "contain a", "a tandem", "tandem of", "of four", "four lrr", "leucine rich", "rich repeat", "domains at", "at the", "the n", "n terminus", "termed d1", "d1 d4", "by six", "six egf", "epidermal growth", "growth factor", "like domains", "a laminin", "laminin g", "g like", "like domain", "three egf", "egf like", "and a", "a c", "c terminal", "terminal cysteine", "cysteine knot", "knot domain.", "domain. most", "most slit", "proteins are", "are cleaved", "cleaved within", "within the", "the egf", "like region", "region by", "by unknown", "unknown proteases", "reviewed by", "by hohenster", "hohenster 2008", "ypsilanti and", "and chedotal", "chedotal 2014", "blockus and", "chedotal 2016", "2016 .", ". nell2", "nell2 is", "is a", "a ligand", "ligand for", "for robo3", "jaworski et", "et al.", "al. 2015", "2015 .

slit", ".

slit protein", "protein binding", "binding modulates", "modulates robo", "robo interactions", "interactions with", "with the", "the cytosolic", "cytosolic adaptors.", "adaptors. the", "cytoplasmic domain", "domain of", "of robo1", "robo2 determines", "determines the", "the repulsive", "repulsive responses", "responses of", "of these", "these receptors.", "receptors. based", "based on", "on the", "the studies", "studies from", "from both", "both invertebrate", "invertebrate and", "and vertebrate", "vertebrate organisms", "organisms it", "it has", "has been", "been inferred", "inferred that", "that robo", "robo induces", "induces growth", "growth cone", "cone repulsion", "repulsion by", "by controlling", "controlling cytoskeletal", "cytoskeletal dynamics", "dynamics via", "via either", "either abelson", "abelson kinase", "and enabled", "or rac1", "rac1 activity", ". while", "while there", "there is", "is some", "some redundancy", "redundancy in", "in the", "the function", "robo1 is", "is implicated", "implicated as", "the predominant", "predominant receptor", "receptor for", "for axon", "axon guidance", "guidance in", "in ventral", "ventral tracts", "robo2 is", "is the", "in dorsal", "dorsal tracts.", "tracts. robo2", "robo2 also", "also repels", "repels neuron", "neuron cell", "cell bodies", "bodies from", "from the", "the floor", "floor plate", "kim et", "al. 2011", "2011 .

in", ".

in addition", "addition to", "to regulating", "regulating axon", "are also", "also implicated", "implicated in", "in regulation", "regulation of", "of proliferation", "proliferation and", "and transition", "transition of", "of primary", "primary to", "to intermediate", "intermediate neuronal", "neuronal progenitors", "progenitors through", "through a", "a poorly", "poorly characterized", "characterized cross", "cross talk", "talk with", "with notch", "notch mediated", "mediated activation", "activation of", "of hes1", "hes1 transcription", "borrell et", "al. 2012", "2012 .

thalamocortical", ".

thalamocortical axon", "axon extension", "extension is", "is regulated", "regulated by", "by neuronal", "neuronal activity", "activity dependent", "dependent transcriptional", "transcriptional regulation", "robo1 transcription.", "transcription. lower", "lower neuronal", "activity correlates", "correlates with", "with increased", "increased robo1", "robo1 transcription", "possibly mediated", "mediated by", "by the", "the nfkb", "nfkb complex", "mire et", "2012 .

it", ".

it is", "is suggested", "suggested that", "that the", "the homeodomain", "homeodomain transcription", "transcription factor", "factor nkx2.9", "nkx2.9 stimulates", "stimulates transcription", "transcription of", "of robo2", "which is", "is involved", "involved in", "of motor", "motor axon", "axon exit", "exit from", "the vertebrate", "vertebrate spinal", "spinal code", "bravo ambrosio", "ambrosio et", "2012 .

of", ".

of the", "the four", "four robo", "robo proteins", "robo4 is", "is not", "not involved", "in neuronal", "neuronal system", "system development", "development but", "but is", "in angiogenesis.", "angiogenesis. the", "the interaction", "interaction of", "of robo4", "robo4 with", "with slit3", "slit3 is", "in proliferation", "motility and", "and chemotaxis", "chemotaxis of", "of endothelial", "endothelial cells", "and accelerates", "accelerates formation", "formation of", "of blood", "blood vessels", "zhang et", "al. 2009", "2009 .", "roundabout robo", "robo family", "family encodes transmembrane", "encodes transmembrane receptors", "transmembrane receptors that", "receptors that regulate", "that regulate axonal", "regulate axonal guidance", "axonal guidance and", "guidance and cell", "and cell migration.", "cell migration. the", "migration. the major", "the major function", "major function of", "function of the", "of the robo", "the robo receptors", "robo receptors is", "receptors is to", "is to mediate", "to mediate repulsion", "mediate repulsion of", "repulsion of the", "of the navigating", "the navigating growth", "navigating growth cones.", "growth cones. there", "cones. there are", "there are four", "are four human", "four human robo", "human robo homologues", "homologues robo1", "robo1 robo2", "robo2 robo3", "robo3 and robo4.", "and robo4. most", "robo4. most of", "most of the", "of the robos", "the robos have", "robos have the", "have the similar", "the similar ectodomain", "similar ectodomain architecture", "ectodomain architecture as", "architecture as the", "as the cell", "the cell adhesion", "cell adhesion molecules", "molecules with", "with five ig", "five ig domains", "ig domains followed", "domains followed by", "followed by three", "by three fn3", "three fn3 repeats", "repeats except", "except for robo4.", "for robo4. robo4", "robo4. robo4 has", "robo4 has two", "has two ig", "two ig and", "ig and two", "and two fn3", "two fn3 repeats.", "fn3 repeats. the", "repeats. the cytoplasmic", "the cytoplasmic domains", "cytoplasmic domains of", "domains of robo", "of robo receptors", "robo receptors are", "receptors are in", "are in general", "in general poorly", "general poorly conserved.", "poorly conserved. however", "however there", "are four short", "four short conserved", "short conserved cytoplasmic", "conserved cytoplasmic sequence", "cytoplasmic sequence motifs", "motifs named", "named cc0 3", "3 that", "that serve as", "serve as binding", "as binding sites", "binding sites for", "sites for adaptor", "for adaptor proteins.", "adaptor proteins. the", "proteins. the ligands", "the ligands for", "ligands for the", "for the human", "the human robo1", "human robo1 and", "robo1 and robo2", "and robo2 receptors", "robo2 receptors are", "receptors are the", "are the three", "the three slit", "three slit proteins", "slit proteins slit1", "slit1 slit2", "slit2 and", "slit3 all", "all of the", "of the slit", "the slit proteins", "slit proteins contain", "proteins contain a", "contain a tandem", "a tandem of", "tandem of four", "of four lrr", "lrr leucine", "leucine rich repeat", "repeat domains", "domains at the", "at the n", "the n terminus", "terminus termed", "termed d1 d4", "d4 followed", "followed by six", "by six egf", "egf epidermal", "epidermal growth factor", "factor like", "domains a", "a laminin g", "laminin g like", "g like domain", "domain alps", "three egf like", "egf like domains", "domains and", "and a c", "a c terminal", "c terminal cysteine", "terminal cysteine knot", "cysteine knot domain.", "knot domain. most", "domain. most slit", "most slit proteins", "slit proteins are", "proteins are cleaved", "are cleaved within", "cleaved within the", "within the egf", "the egf like", "egf like region", "like region by", "region by unknown", "by unknown proteases", "proteases reviewed", "reviewed by hohenster", "by hohenster 2008", "2008 ypsilanti", "ypsilanti and chedotal", "and chedotal 2014", "2014 blockus", "blockus and chedotal", "and chedotal 2016", "chedotal 2016 .", "2016 . nell2", ". nell2 is", "nell2 is a", "is a ligand", "a ligand for", "ligand for robo3", "robo3 jaworski", "jaworski et al.", "et al. 2015", "al. 2015 .

slit", "2015 .

slit protein", ".

slit protein binding", "protein binding modulates", "binding modulates robo", "modulates robo interactions", "robo interactions with", "interactions with the", "with the cytosolic", "the cytosolic adaptors.", "cytosolic adaptors. the", "adaptors. the cytoplasmic", "the cytoplasmic domain", "cytoplasmic domain of", "domain of robo1", "of robo1 and", "and robo2 determines", "robo2 determines the", "determines the repulsive", "the repulsive responses", "repulsive responses of", "responses of these", "of these receptors.", "these receptors. based", "receptors. based on", "based on the", "on the studies", "the studies from", "studies from both", "from both invertebrate", "both invertebrate and", "invertebrate and vertebrate", "and vertebrate organisms", "vertebrate organisms it", "organisms it has", "it has been", "has been inferred", "been inferred that", "inferred that robo", "that robo induces", "robo induces growth", "induces growth cone", "growth cone repulsion", "cone repulsion by", "repulsion by controlling", "by controlling cytoskeletal", "controlling cytoskeletal dynamics", "cytoskeletal dynamics via", "dynamics via either", "via either abelson", "either abelson kinase", "kinase abl", "abl and", "enabled ena", "or rac1 activity", "activity reviewed", "2016 . while", ". while there", "while there is", "there is some", "is some redundancy", "some redundancy in", "redundancy in the", "in the function", "the function of", "function of robo", "receptors robo1", "robo1 is implicated", "is implicated as", "implicated as the", "as the predominant", "the predominant receptor", "predominant receptor for", "receptor for axon", "for axon guidance", "axon guidance in", "guidance in ventral", "in ventral tracts", "tracts and", "and robo2 is", "robo2 is the", "is the predominant", "guidance in dorsal", "in dorsal tracts.", "dorsal tracts. robo2", "tracts. robo2 also", "robo2 also repels", "also repels neuron", "repels neuron cell", "neuron cell bodies", "cell bodies from", "bodies from the", "from the floor", "the floor plate", "plate kim", "kim et al.", "et al. 2011", "al. 2011 .

in", "2011 .

in addition", ".

in addition to", "addition to regulating", "to regulating axon", "regulating axon guidance", "guidance robo1", "receptors are also", "are also implicated", "also implicated in", "implicated in regulation", "in regulation of", "regulation of proliferation", "of proliferation and", "proliferation and transition", "and transition of", "transition of primary", "of primary to", "primary to intermediate", "to intermediate neuronal", "intermediate neuronal progenitors", "neuronal progenitors through", "progenitors through a", "through a poorly", "a poorly characterized", "poorly characterized cross", "characterized cross talk", "cross talk with", "talk with notch", "with notch mediated", "notch mediated activation", "mediated activation of", "activation of hes1", "of hes1 transcription", "transcription borrell", "borrell et al.", "et al. 2012", "al. 2012 .

thalamocortical", "2012 .

thalamocortical axon", ".

thalamocortical axon extension", "axon extension is", "extension is regulated", "is regulated by", "regulated by neuronal", "by neuronal activity", "neuronal activity dependent", "activity dependent transcriptional", "dependent transcriptional regulation", "transcriptional regulation of", "regulation of robo1", "of robo1 transcription.", "robo1 transcription. lower", "transcription. lower neuronal", "lower neuronal activity", "neuronal activity correlates", "activity correlates with", "correlates with increased", "with increased robo1", "increased robo1 transcription", "transcription possibly", "possibly mediated by", "mediated by the", "by the nfkb", "the nfkb complex", "complex mire", "mire et al.", "al. 2012 .

it", "2012 .

it is", ".

it is suggested", "is suggested that", "suggested that the", "that the homeodomain", "the homeodomain transcription", "homeodomain transcription factor", "transcription factor nkx2.9", "factor nkx2.9 stimulates", "nkx2.9 stimulates transcription", "stimulates transcription of", "transcription of robo2", "robo2 which", "which is involved", "is involved in", "involved in regulation", "regulation of motor", "of motor axon", "motor axon exit", "axon exit from", "exit from the", "from the vertebrate", "the vertebrate spinal", "vertebrate spinal code", "code bravo", "bravo ambrosio et", "ambrosio et al.", "al. 2012 .

of", "2012 .

of the", ".

of the four", "the four robo", "four robo proteins", "proteins robo4", "robo4 is not", "is not involved", "not involved in", "involved in neuronal", "in neuronal system", "neuronal system development", "system development but", "development but is", "is instead", "instead involved", "involved in angiogenesis.", "in angiogenesis. the", "angiogenesis. the interaction", "the interaction of", "interaction of robo4", "of robo4 with", "robo4 with slit3", "with slit3 is", "slit3 is involved", "involved in proliferation", "proliferation motility", "motility and chemotaxis", "and chemotaxis of", "chemotaxis of endothelial", "of endothelial cells", "cells and", "and accelerates formation", "accelerates formation of", "formation of blood", "of blood vessels", "vessels zhang", "zhang et al.", "et al. 2009", "al. 2009 .", "the roundabout robo", "robo family encodes", "family encodes transmembrane receptors", "encodes transmembrane receptors that", "transmembrane receptors that regulate", "receptors that regulate axonal", "that regulate axonal guidance", "regulate axonal guidance and", "axonal guidance and cell", "guidance and cell migration.", "and cell migration. the", "cell migration. the major", "migration. the major function", "the major function of", "major function of the", "function of the robo", "of the robo receptors", "the robo receptors is", "robo receptors is to", "receptors is to mediate", "is to mediate repulsion", "to mediate repulsion of", "mediate repulsion of the", "repulsion of the navigating", "of the navigating growth", "the navigating growth cones.", "navigating growth cones. there", "growth cones. there are", "cones. there are four", "there are four human", "are four human robo", "four human robo homologues", "robo homologues robo1", "robo2 robo3 and", "robo3 and robo4. most", "and robo4. most of", "robo4. most of the", "most of the robos", "of the robos have", "the robos have the", "robos have the similar", "have the similar ectodomain", "the similar ectodomain architecture", "similar ectodomain architecture as", "ectodomain architecture as the", "architecture as the cell", "as the cell adhesion", "the cell adhesion molecules", "adhesion molecules with", "molecules with five", "with five ig domains", "five ig domains followed", "ig domains followed by", "domains followed by three", "followed by three fn3", "by three fn3 repeats", "fn3 repeats except", "repeats except for", "except for robo4. robo4", "for robo4. robo4 has", "robo4. robo4 has two", "robo4 has two ig", "has two ig and", "two ig and two", "ig and two fn3", "and two fn3 repeats.", "two fn3 repeats. the", "fn3 repeats. the cytoplasmic", "repeats. the cytoplasmic domains", "the cytoplasmic domains of", "cytoplasmic domains of robo", "domains of robo receptors", "of robo receptors are", "robo receptors are in", "receptors are in general", "are in general poorly", "in general poorly conserved.", "general poorly conserved. however", "conserved. however there", "however there are", "there are four short", "are four short conserved", "four short conserved cytoplasmic", "short conserved cytoplasmic sequence", "conserved cytoplasmic sequence motifs", "sequence motifs named", "motifs named cc0", "cc0 3 that", "3 that serve", "that serve as binding", "serve as binding sites", "as binding sites for", "binding sites for adaptor", "sites for adaptor proteins.", "for adaptor proteins. the", "adaptor proteins. the ligands", "proteins. the ligands for", "the ligands for the", "ligands for the human", "for the human robo1", "the human robo1 and", "human robo1 and robo2", "robo1 and robo2 receptors", "and robo2 receptors are", "robo2 receptors are the", "receptors are the three", "are the three slit", "the three slit proteins", "three slit proteins slit1", "proteins slit1 slit2", "slit2 and slit3", "and slit3 all", "slit3 all of", "all of the slit", "of the slit proteins", "the slit proteins contain", "slit proteins contain a", "proteins contain a tandem", "contain a tandem of", "a tandem of four", "tandem of four lrr", "four lrr leucine", "lrr leucine rich", "rich repeat domains", "repeat domains at", "domains at the n", "at the n terminus", "n terminus termed", "terminus termed d1", "d1 d4 followed", "d4 followed by", "followed by six egf", "six egf epidermal", "egf epidermal growth", "growth factor like", "factor like domains", "like domains a", "domains a laminin", "a laminin g like", "laminin g like domain", "like domain alps", "alps three", "three egf like domains", "like domains and", "domains and a", "and a c terminal", "a c terminal cysteine", "c terminal cysteine knot", "terminal cysteine knot domain.", "cysteine knot domain. most", "knot domain. most slit", "domain. most slit proteins", "most slit proteins are", "slit proteins are cleaved", "proteins are cleaved within", "are cleaved within the", "cleaved within the egf", "within the egf like", "the egf like region", "egf like region by", "like region by unknown", "region by unknown proteases", "unknown proteases reviewed", "proteases reviewed by", "reviewed by hohenster 2008", "hohenster 2008 ypsilanti", "2008 ypsilanti and", "ypsilanti and chedotal 2014", "chedotal 2014 blockus", "2014 blockus and", "blockus and chedotal 2016", "and chedotal 2016 .", "chedotal 2016 . nell2", "2016 . nell2 is", ". nell2 is a", "nell2 is a ligand", "is a ligand for", "a ligand for robo3", "for robo3 jaworski", "robo3 jaworski et", "jaworski et al. 2015", "et al. 2015 .

slit", "al. 2015 .

slit protein", "2015 .

slit protein binding", ".

slit protein binding modulates", "protein binding modulates robo", "binding modulates robo interactions", "modulates robo interactions with", "robo interactions with the", "interactions with the cytosolic", "with the cytosolic adaptors.", "the cytosolic adaptors. the", "cytosolic adaptors. the cytoplasmic", "adaptors. the cytoplasmic domain", "the cytoplasmic domain of", "cytoplasmic domain of robo1", "domain of robo1 and", "of robo1 and robo2", "robo1 and robo2 determines", "and robo2 determines the", "robo2 determines the repulsive", "determines the repulsive responses", "the repulsive responses of", "repulsive responses of these", "responses of these receptors.", "of these receptors. based", "these receptors. based on", "receptors. based on the", "based on the studies", "on the studies from", "the studies from both", "studies from both invertebrate", "from both invertebrate and", "both invertebrate and vertebrate", "invertebrate and vertebrate organisms", "and vertebrate organisms it", "vertebrate organisms it has", "organisms it has been", "it has been inferred", "has been inferred that", "been inferred that robo", "inferred that robo induces", "that robo induces growth", "robo induces growth cone", "induces growth cone repulsion", "growth cone repulsion by", "cone repulsion by controlling", "repulsion by controlling cytoskeletal", "by controlling cytoskeletal dynamics", "controlling cytoskeletal dynamics via", "cytoskeletal dynamics via either", "dynamics via either abelson", "via either abelson kinase", "abelson kinase abl", "abl and enabled", "and enabled ena", "ena or", "rac1 activity reviewed", "activity reviewed by", "chedotal 2016 . while", "2016 . while there", ". while there is", "while there is some", "there is some redundancy", "is some redundancy in", "some redundancy in the", "redundancy in the function", "in the function of", "the function of robo", "function of robo receptors", "robo receptors robo1", "receptors robo1 is", "robo1 is implicated as", "is implicated as the", "implicated as the predominant", "as the predominant receptor", "the predominant receptor for", "predominant receptor for axon", "receptor for axon guidance", "for axon guidance in", "axon guidance in ventral", "guidance in ventral tracts", "ventral tracts and", "tracts and robo2", "and robo2 is the", "robo2 is the predominant", "is the predominant receptor", "axon guidance in dorsal", "guidance in dorsal tracts.", "in dorsal tracts. robo2", "dorsal tracts. robo2 also", "tracts. robo2 also repels", "robo2 also repels neuron", "also repels neuron cell", "repels neuron cell bodies", "neuron cell bodies from", "cell bodies from the", "bodies from the floor", "from the floor plate", "floor plate kim", "plate kim et", "kim et al. 2011", "et al. 2011 .

in", "al. 2011 .

in addition", "2011 .

in addition to", ".

in addition to regulating", "addition to regulating axon", "to regulating axon guidance", "axon guidance robo1", "guidance robo1 and", "robo2 receptors are also", "receptors are also implicated", "are also implicated in", "also implicated in regulation", "implicated in regulation of", "in regulation of proliferation", "regulation of proliferation and", "of proliferation and transition", "proliferation and transition of", "and transition of primary", "transition of primary to", "of primary to intermediate", "primary to intermediate neuronal", "to intermediate neuronal progenitors", "intermediate neuronal progenitors through", "neuronal progenitors through a", "progenitors through a poorly", "through a poorly characterized", "a poorly characterized cross", "poorly characterized cross talk", "characterized cross talk with", "cross talk with notch", "talk with notch mediated", "with notch mediated activation", "notch mediated activation of", "mediated activation of hes1", "activation of hes1 transcription", "hes1 transcription borrell", "transcription borrell et", "borrell et al. 2012", "et al. 2012 .

thalamocortical", "al. 2012 .

thalamocortical axon", "2012 .

thalamocortical axon extension", ".

thalamocortical axon extension is", "axon extension is regulated", "extension is regulated by", "is regulated by neuronal", "regulated by neuronal activity", "by neuronal activity dependent", "neuronal activity dependent transcriptional", "activity dependent transcriptional regulation", "dependent transcriptional regulation of", "transcriptional regulation of robo1", "regulation of robo1 transcription.", "of robo1 transcription. lower", "robo1 transcription. lower neuronal", "transcription. lower neuronal activity", "lower neuronal activity correlates", "neuronal activity correlates with", "activity correlates with increased", "correlates with increased robo1", "with increased robo1 transcription", "robo1 transcription possibly", "transcription possibly mediated", "possibly mediated by the", "mediated by the nfkb", "by the nfkb complex", "nfkb complex mire", "complex mire et", "mire et al. 2012", "et al. 2012 .

it", "al. 2012 .

it is", "2012 .

it is suggested", ".

it is suggested that", "is suggested that the", "suggested that the homeodomain", "that the homeodomain transcription", "the homeodomain transcription factor", "homeodomain transcription factor nkx2.9", "transcription factor nkx2.9 stimulates", "factor nkx2.9 stimulates transcription", "nkx2.9 stimulates transcription of", "stimulates transcription of robo2", "of robo2 which", "robo2 which is", "which is involved in", "is involved in regulation", "involved in regulation of", "in regulation of motor", "regulation of motor axon", "of motor axon exit", "motor axon exit from", "axon exit from the", "exit from the vertebrate", "from the vertebrate spinal", "the vertebrate spinal code", "spinal code bravo", "code bravo ambrosio", "bravo ambrosio et al.", "ambrosio et al. 2012", "et al. 2012 .

of", "al. 2012 .

of the", "2012 .

of the four", ".

of the four robo", "the four robo proteins", "robo proteins robo4", "proteins robo4 is", "robo4 is not involved", "is not involved in", "not involved in neuronal", "involved in neuronal system", "in neuronal system development", "neuronal system development but", "system development but is", "but is instead", "instead involved in", "involved in angiogenesis. the", "in angiogenesis. the interaction", "angiogenesis. the interaction of", "the interaction of robo4", "interaction of robo4 with", "of robo4 with slit3", "robo4 with slit3 is", "with slit3 is involved", "slit3 is involved in", "is involved in proliferation", "in proliferation motility", "proliferation motility and", "motility and chemotaxis of", "and chemotaxis of endothelial", "chemotaxis of endothelial cells", "endothelial cells and", "cells and accelerates", "and accelerates formation of", "accelerates formation of blood", "formation of blood vessels", "blood vessels zhang", "vessels zhang et", "zhang et al. 2009", "et al. 2009 .", "roundabout robo family", "robo family encodes transmembrane", "family encodes transmembrane receptors that", "encodes transmembrane receptors that regulate", "transmembrane receptors that regulate axonal", "receptors that regulate axonal guidance", "that regulate axonal guidance and", "regulate axonal guidance and cell", "axonal guidance and cell migration.", "guidance and cell migration. the", "and cell migration. the major", "cell migration. the major function", "migration. the major function of", "the major function of the", "major function of the robo", "function of the robo receptors", "of the robo receptors is", "the robo receptors is to", "robo receptors is to mediate", "receptors is to mediate repulsion", "is to mediate repulsion of", "to mediate repulsion of the", "mediate repulsion of the navigating", "repulsion of the navigating growth", "of the navigating growth cones.", "the navigating growth cones. there", "navigating growth cones. there are", "growth cones. there are four", "cones. there are four human", "there are four human robo", "are four human robo homologues", "human robo homologues robo1", "homologues robo1 robo2", "robo1 robo2 robo3", "robo2 robo3 and robo4.", "robo3 and robo4. most of", "and robo4. most of the", "robo4. most of the robos", "most of the robos have", "of the robos have the", "the robos have the similar", "robos have the similar ectodomain", "have the similar ectodomain architecture", "the similar ectodomain architecture as", "similar ectodomain architecture as the", "ectodomain architecture as the cell", "architecture as the cell adhesion", "as the cell adhesion molecules", "cell adhesion molecules with", "adhesion molecules with five", "molecules with five ig", "with five ig domains followed", "five ig domains followed by", "ig domains followed by three", "domains followed by three fn3", "followed by three fn3 repeats", "three fn3 repeats except", "fn3 repeats except for", "repeats except for robo4.", "except for robo4. robo4 has", "for robo4. robo4 has two", "robo4. robo4 has two ig", "robo4 has two ig and", "has two ig and two", "two ig and two fn3", "ig and two fn3 repeats.", "and two fn3 repeats. the", "two fn3 repeats. the cytoplasmic", "fn3 repeats. the cytoplasmic domains", "repeats. the cytoplasmic domains of", "the cytoplasmic domains of robo", "cytoplasmic domains of robo receptors", "domains of robo receptors are", "of robo receptors are in", "robo receptors are in general", "receptors are in general poorly", "are in general poorly conserved.", "in general poorly conserved. however", "poorly conserved. however there", "conserved. however there are", "however there are four", "there are four short conserved", "are four short conserved cytoplasmic", "four short conserved cytoplasmic sequence", "short conserved cytoplasmic sequence motifs", "cytoplasmic sequence motifs named", "sequence motifs named cc0", "motifs named cc0 3", "named cc0 3 that", "cc0 3 that serve", "3 that serve as", "that serve as binding sites", "serve as binding sites for", "as binding sites for adaptor", "binding sites for adaptor proteins.", "sites for adaptor proteins. the", "for adaptor proteins. the ligands", "adaptor proteins. the ligands for", "proteins. the ligands for the", "the ligands for the human", "ligands for the human robo1", "for the human robo1 and", "the human robo1 and robo2", "human robo1 and robo2 receptors", "robo1 and robo2 receptors are", "and robo2 receptors are the", "robo2 receptors are the three", "receptors are the three slit", "are the three slit proteins", "the three slit proteins slit1", "slit proteins slit1 slit2", "slit1 slit2 and", "and slit3 all of", "slit3 all of the", "all of the slit proteins", "of the slit proteins contain", "the slit proteins contain a", "slit proteins contain a tandem", "proteins contain a tandem of", "contain a tandem of four", "a tandem of four lrr", "of four lrr leucine", "four lrr leucine rich", "lrr leucine rich repeat", "leucine rich repeat domains", "rich repeat domains at", "repeat domains at the", "domains at the n terminus", "the n terminus termed", "n terminus termed d1", "terminus termed d1 d4", "termed d1 d4 followed", "d1 d4 followed by", "d4 followed by six", "by six egf epidermal", "six egf epidermal growth", "egf epidermal growth factor", "epidermal growth factor like", "growth factor like domains", "like domains a laminin", "domains a laminin g", "a laminin g like domain", "g like domain alps", "alps three egf", "egf like domains and", "like domains and a", "domains and a c", "and a c terminal cysteine", "a c terminal cysteine knot", "c terminal cysteine knot domain.", "terminal cysteine knot domain. most", "cysteine knot domain. most slit", "knot domain. most slit proteins", "domain. most slit proteins are", "most slit proteins are cleaved", "slit proteins are cleaved within", "proteins are cleaved within the", "are cleaved within the egf", "cleaved within the egf like", "within the egf like region", "the egf like region by", "egf like region by unknown", "like region by unknown proteases", "by unknown proteases reviewed", "unknown proteases reviewed by", "proteases reviewed by hohenster", "by hohenster 2008 ypsilanti", "hohenster 2008 ypsilanti and", "2008 ypsilanti and chedotal", "and chedotal 2014 blockus", "chedotal 2014 blockus and", "2014 blockus and chedotal", "blockus and chedotal 2016 .", "and chedotal 2016 . nell2", "chedotal 2016 . nell2 is", "2016 . nell2 is a", ". nell2 is a ligand", "nell2 is a ligand for", "is a ligand for robo3", "ligand for robo3 jaworski", "for robo3 jaworski et", "robo3 jaworski et al.", "jaworski et al. 2015 .

slit", "et al. 2015 .

slit protein", "al. 2015 .

slit protein binding", "2015 .

slit protein binding modulates", ".

slit protein binding modulates robo", "protein binding modulates robo interactions", "binding modulates robo interactions with", "modulates robo interactions with the", "robo interactions with the cytosolic", "interactions with the cytosolic adaptors.", "with the cytosolic adaptors. the", "the cytosolic adaptors. the cytoplasmic", "cytosolic adaptors. the cytoplasmic domain", "adaptors. the cytoplasmic domain of", "the cytoplasmic domain of robo1", "cytoplasmic domain of robo1 and", "domain of robo1 and robo2", "of robo1 and robo2 determines", "robo1 and robo2 determines the", "and robo2 determines the repulsive", "robo2 determines the repulsive responses", "determines the repulsive responses of", "the repulsive responses of these", "repulsive responses of these receptors.", "responses of these receptors. based", "of these receptors. based on", "these receptors. based on the", "receptors. based on the studies", "based on the studies from", "on the studies from both", "the studies from both invertebrate", "studies from both invertebrate and", "from both invertebrate and vertebrate", "both invertebrate and vertebrate organisms", "invertebrate and vertebrate organisms it", "and vertebrate organisms it has", "vertebrate organisms it has been", "organisms it has been inferred", "it has been inferred that", "has been inferred that robo", "been inferred that robo induces", "inferred that robo induces growth", "that robo induces growth cone", "robo induces growth cone repulsion", "induces growth cone repulsion by", "growth cone repulsion by controlling", "cone repulsion by controlling cytoskeletal", "repulsion by controlling cytoskeletal dynamics", "by controlling cytoskeletal dynamics via", "controlling cytoskeletal dynamics via either", "cytoskeletal dynamics via either abelson", "dynamics via either abelson kinase", "either abelson kinase abl", "kinase abl and", "ena or rac1", "or rac1 activity reviewed", "rac1 activity reviewed by", "activity reviewed by hohenster", "and chedotal 2016 . while", "chedotal 2016 . while there", "2016 . while there is", ". while there is some", "while there is some redundancy", "there is some redundancy in", "is some redundancy in the", "some redundancy in the function", "redundancy in the function of", "in the function of robo", "the function of robo receptors", "of robo receptors robo1", "robo receptors robo1 is", "receptors robo1 is implicated", "robo1 is implicated as the", "is implicated as the predominant", "implicated as the predominant receptor", "as the predominant receptor for", "the predominant receptor for axon", "predominant receptor for axon guidance", "receptor for axon guidance in", "for axon guidance in ventral", "axon guidance in ventral tracts", "in ventral tracts and", "ventral tracts and robo2", "tracts and robo2 is", "and robo2 is the predominant", "robo2 is the predominant receptor", "is the predominant receptor for", "for axon guidance in dorsal", "axon guidance in dorsal tracts.", "guidance in dorsal tracts. robo2", "in dorsal tracts. robo2 also", "dorsal tracts. robo2 also repels", "tracts. robo2 also repels neuron", "robo2 also repels neuron cell", "also repels neuron cell bodies", "repels neuron cell bodies from", "neuron cell bodies from the", "cell bodies from the floor", "bodies from the floor plate", "the floor plate kim", "floor plate kim et", "plate kim et al.", "kim et al. 2011 .

in", "et al. 2011 .

in addition", "al. 2011 .

in addition to", "2011 .

in addition to regulating", ".

in addition to regulating axon", "addition to regulating axon guidance", "regulating axon guidance robo1", "axon guidance robo1 and", "guidance robo1 and robo2", "and robo2 receptors are also", "robo2 receptors are also implicated", "receptors are also implicated in", "are also implicated in regulation", "also implicated in regulation of", "implicated in regulation of proliferation", "in regulation of proliferation and", "regulation of proliferation and transition", "of proliferation and transition of", "proliferation and transition of primary", "and transition of primary to", "transition of primary to intermediate", "of primary to intermediate neuronal", "primary to intermediate neuronal progenitors", "to intermediate neuronal progenitors through", "intermediate neuronal progenitors through a", "neuronal progenitors through a poorly", "progenitors through a poorly characterized", "through a poorly characterized cross", "a poorly characterized cross talk", "poorly characterized cross talk with", "characterized cross talk with notch", "cross talk with notch mediated", "talk with notch mediated activation", "with notch mediated activation of", "notch mediated activation of hes1", "mediated activation of hes1 transcription", "of hes1 transcription borrell", "hes1 transcription borrell et", "transcription borrell et al.", "borrell et al. 2012 .

thalamocortical", "et al. 2012 .

thalamocortical axon", "al. 2012 .

thalamocortical axon extension", "2012 .

thalamocortical axon extension is", ".

thalamocortical axon extension is regulated", "axon extension is regulated by", "extension is regulated by neuronal", "is regulated by neuronal activity", "regulated by neuronal activity dependent", "by neuronal activity dependent transcriptional", "neuronal activity dependent transcriptional regulation", "activity dependent transcriptional regulation of", "dependent transcriptional regulation of robo1", "transcriptional regulation of robo1 transcription.", "regulation of robo1 transcription. lower", "of robo1 transcription. lower neuronal", "robo1 transcription. lower neuronal activity", "transcription. lower neuronal activity correlates", "lower neuronal activity correlates with", "neuronal activity correlates with increased", "activity correlates with increased robo1", "correlates with increased robo1 transcription", "increased robo1 transcription possibly", "robo1 transcription possibly mediated", "transcription possibly mediated by", "possibly mediated by the nfkb", "mediated by the nfkb complex", "the nfkb complex mire", "nfkb complex mire et", "complex mire et al.", "mire et al. 2012 .

it", "et al. 2012 .

it is", "al. 2012 .

it is suggested", "2012 .

it is suggested that", ".

it is suggested that the", "is suggested that the homeodomain", "suggested that the homeodomain transcription", "that the homeodomain transcription factor", "the homeodomain transcription factor nkx2.9", "homeodomain transcription factor nkx2.9 stimulates", "transcription factor nkx2.9 stimulates transcription", "factor nkx2.9 stimulates transcription of", "nkx2.9 stimulates transcription of robo2", "transcription of robo2 which", "of robo2 which is", "robo2 which is involved", "which is involved in regulation", "is involved in regulation of", "involved in regulation of motor", "in regulation of motor axon", "regulation of motor axon exit", "of motor axon exit from", "motor axon exit from the", "axon exit from the vertebrate", "exit from the vertebrate spinal", "from the vertebrate spinal code", "vertebrate spinal code bravo", "spinal code bravo ambrosio", "code bravo ambrosio et", "bravo ambrosio et al. 2012", "ambrosio et al. 2012 .

of", "et al. 2012 .

of the", "al. 2012 .

of the four", "2012 .

of the four robo", ".

of the four robo proteins", "four robo proteins robo4", "robo proteins robo4 is", "proteins robo4 is not", "robo4 is not involved in", "is not involved in neuronal", "not involved in neuronal system", "involved in neuronal system development", "in neuronal system development but", "neuronal system development but is", "development but is instead", "is instead involved", "instead involved in angiogenesis.", "involved in angiogenesis. the interaction", "in angiogenesis. the interaction of", "angiogenesis. the interaction of robo4", "the interaction of robo4 with", "interaction of robo4 with slit3", "of robo4 with slit3 is", "robo4 with slit3 is involved", "with slit3 is involved in", "slit3 is involved in proliferation", "involved in proliferation motility", "in proliferation motility and", "proliferation motility and chemotaxis", "motility and chemotaxis of endothelial", "and chemotaxis of endothelial cells", "of endothelial cells and", "endothelial cells and accelerates", "cells and accelerates formation", "and accelerates formation of blood", "accelerates formation of blood vessels", "of blood vessels zhang", "blood vessels zhang et", "vessels zhang et al.", "zhang et al. 2009 ." ] }, { "record_id": "GLY_000594_1_294", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3769402", "r hsa", "hsa 3769402", "r hsa 3769402" ] }, { "record_id": "GLY_000594_1_294", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "deactivation of", "of the", "the beta", "beta catenin", "catenin transactivating", "transactivating complex", "deactivation of the", "of the beta", "the beta catenin", "beta catenin transactivating", "catenin transactivating complex", "deactivation of the beta", "of the beta catenin", "the beta catenin transactivating", "beta catenin transactivating complex", "deactivation of the beta catenin", "of the beta catenin transactivating", "the beta catenin transactivating 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al", "al 2006", "2006 . it", ". it is", "it is worth", "is worth noting", "worth noting that", "noting that while", "that while some", "while some of", "some of the", "of the players", "the players involved", "players involved in", "involved in the", "transactivating complex are", "complex are beginning", "are beginning to", "beginning to be", "to be worked", "be worked out", "worked out in", "out in vitro", "vitro the", "the significance of", "significance of their", "of their role", "their role in", "role in vivo", "in vivo is", "vivo is not", "is not yet", "not yet fully", "yet fully understood", "understood and", "and some can", "some can be", "can be knocked", "be knocked out", "knocked out with", "out with little", "with little effect", "little effect on", "effect on endogenous", "on endogenous wnt", "endogenous wnt signaling", "signaling see", "see for instance", "for instance voronina", "instance voronina et", "voronina et al", "al 2009", "the mechanisms involved in", 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understood. beta catenin is", "understood. beta catenin is known", "beta catenin is known to", "catenin is known to recruit", "is known to recruit a", "known to recruit a number", "to recruit a number of", "recruit a number of transcriptional", "a number of transcriptional repressors", "of transcriptional repressors including", "transcriptional repressors including reptin", "including reptin smrt and", "reptin smrt and ncor", "smrt and ncor to", "and ncor to the", "ncor to the tcf/lef", "the tcf/lef complex allowing", "tcf/lef complex allowing the", "complex allowing the transition", "allowing the transition from activation", "the transition from activation to", "transition from activation to repression", "activation to repression bauer", "to repression bauer et", "repression bauer et al", "bauer et al 2000", "al 2000 weiske", "2000 weiske et al", "weiske et al 2007", "al 2007 song", "2007 song and gelmann", "song and gelmann 2008", "and gelmann 2008 .", ". ctnnbip1 also", "ctnnbip1 also known as", "known as icat and", "as icat and chibby", "icat and chibby are", "and chibby are inhibitors of", "chibby are inhibitors of tcf", "are inhibitors of tcf dependent", "inhibitors of tcf dependent signaling", "of tcf dependent signaling that", "tcf dependent signaling that function", "dependent signaling that function by", "signaling that function by binding", "that function by binding directly", "function by binding directly to", "by binding directly to beta", "binding directly to beta catenin", "directly to beta catenin and", "to beta catenin and preventing", "beta catenin and preventing interactions", "catenin and preventing interactions with", "and preventing interactions with critical", "preventing interactions with critical components", "interactions with critical components of", "with critical components of the", "critical components of the transactivation", "components of the transactivation machinery", "the transactivation machinery takemaru", "transactivation 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dickkopf", "2008 .

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"ramp4 p58ipk and", "p58ipk and others. this", "and others. this results in", "others. this results in an", "this results in an increase", "results in an increase in", "in an increase in protein", "an increase in protein folding", "increase in protein folding activity", "in protein folding activity in", "protein folding activity in the", "folding activity in the er." ] }, { "record_id": "GLY_000594_1_301", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "381340", "r hsa", "hsa 381340", "r hsa 381340" ] }, { "record_id": "GLY_000594_1_301", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation of", "of white", "white adipocyte", "adipocyte differentiation", "transcriptional regulation of", "regulation of white", "of white adipocyte", "white adipocyte differentiation", "transcriptional regulation of white", "regulation of white adipocyte", "of white adipocyte differentiation", "transcriptional regulation of white adipocyte", "regulation of white adipocyte differentiation", "adipogenesis is", "is the", "the process", "process of", "of cell", "cell differentiation", "differentiation by", "by which", "which preadipocytes", "preadipocytes become", "become adipocytes.", "adipocytes. during", "during this", "this process", "process the", "the preadipocytes", "preadipocytes cease", "cease to", "to proliferate", "begin to", "to accumulate", "accumulate lipid", "lipid droplets", "droplets and", "and develop", "develop morphologic", "morphologic and", "and biochemical", "biochemical characteristics", "characteristics of", "of mature", "mature adipocytes", "adipocytes such", "such as", "as hormone", "hormone responsive", "responsive lipogenenic", "lipogenenic and", "and lipolytic", "lipolytic programs.", "programs. the", "the most", "most intensively", "intensively studied", "studied model", "model system", "system for", "for adipogenesis", "is differentiation", "differentiation of", "of the", "the mouse", "mouse 3t3", "3t3 l1", "l1 preadipocyte", "preadipocyte cell", "cell line", "line by", "by an", "an induction", "induction cocktail", "cocktail of", "of containing", "containing mitogens", "an inducer", "inducer of", "of camp", "and fetal", "fetal serum", "cao et", "et al.", "al. 1991", "reviewed in", "in farmer", "farmer 2006", "2006 .", ". more", "more recently", "recently additional", "additional cellular", "cellular models", "models have", "have become", "become available", "available to", "to study", "study adipogenesis", "adipogenesis that", "that involve", "involve almost", "almost all", "all stages", "stages of", "of development", "in rosen", "rosen and", "and macdougald", "macdougald 2006", ". in", "in vivo", "vivo knockout", "knockout mice", "mice lacking", "lacking putative", "putative adipogenic", "adipogenic factors", "factors have", "have also", "also been", "been extensively", "extensively studied.", "studied. human", "human pathways", "pathways are", "are traditionally", "traditionally inferred", "inferred from", "from those", "those discovered", "discovered in", "in mouse", "mouse but", "but are", "are now", "now beginning", "beginning to", "to be", "be validated", "validated in", "in cellular", "models derived", "derived from", "from human", "human adipose", "adipose progenitors", "fischer posovszky", "posovszky et", "al. 2008", "wdziekonski et", "al. 2011", "2011 .
adipogenesis", ".
adipogenesis is", "is controlled", "controlled by", "by a", "a cascade", "cascade of", "of transcription", "transcription factors", "yeh et", "al. 1995", "gesta et", "al. 2007", "2007 .", ". one", "one of", "the first", "first observable", "observable events", "events during", "during adipocyte", "differentiation is", "is a", "a transient", "transient increase", "increase in", "in expression", "expression of", "the cebpb", "ccaat/enhancer binding", "binding protein", "protein beta", "and cebpd", "in lane", "lane et", "al. 1999", "1999 .", ". this", "this occurs", "occurs prior", "prior to", "to the", "the accumulation", "accumulation of", "of lipid", "lipid droplets.", "droplets. however", "it is", "the subsequent", "subsequent inductions", "inductions of", "of cebpa", "cebpa and", "and pparg", "pparg that", "that are", "are critical", "critical for", "for morphological", "biochemical and", "and functional", "functional adipocytes.
ectopic", "adipocytes.
ectopic expression", "of cebpb", "cebpb alone", "alone is", "is capable", "capable of", "of inducing", "inducing substantial", "substantial adipocyte", "differentiation in", "in fibroblasts", "fibroblasts while", "while cebpd", "cebpd has", "has a", "a minimal", "minimal effect.", "effect. cebpb", "cebpb is", "is upregulated", "upregulated in", "in response", "response to", "to intracellular", "intracellular camp", "possibly via", "via pcreb", "and serum", "serum mitogens", "via krox20", "krox20 .", ". cebpd", "cebpd is", "to glucocorticoids.", "glucocorticoids. the", "the exact", "exact mechanisms", "mechanisms that", "that upregulate", "upregulate the", "the cebps", "cebps are", "are not", "not fully", "fully known.
cebpb", "known.
cebpb and", "cebpd act", "act directly", "directly on", "on the", "the peroxisome", "peroxisome proliferator", "proliferator activated", "activated receptor", "receptor gamma", "gene by", "by binding", "binding its", "its promoter", "promoter and", "and activating", "activating transcription.", "transcription. cebpb", "cebpb and", "cebpd also", "also directly", "directly activate", "activate the", "the ebf1", "ebf1 gene", "and possibly", "possibly other", "other ebfs", "and klf5", "jimenez et", "oishi 2005", "2005 .", ". the", "ebf1 and", "klf5 proteins", "in turn", "turn bind", "and activate", "the pparg", "pparg promoter.", "promoter. other", "other hormones", "as insulin", "affect pparg", "pparg expression", "expression and", "and other", "other transcription", "as add1/srebp1c", "bind the", "promoter. this", "this is", "is an", "an area", "area of", "of ongoing", "ongoing research.
during", "research.
during adipogenesis", "adipogenesis the", "pparg gene", "gene is", "is transcribed", "transcribed to", "to yield", "yield 2", "2 variants.", "variants. the", "the adipogenic", "adipogenic variant", "variant 2", "2 mrna", "mrna encodes", "encodes 30", "30 additional", "additional amino", "amino acids", "acids at", "at the", "the n", "n terminus", "terminus compared", "compared to", "the widely", "widely expressed", "expressed variant", "variant 1", "1 mrna.
pparg", "mrna.
pparg encodes", "encodes a", "a type", "type ii", "ii nuclear", "nuclear hormone", "hormone receptor", "remains in", "in the", "the nucleus", "nucleus in", "the absence", "absence of", "of ligand", "that forms", "forms a", "a heterodimer", "heterodimer with", "with the", "the retinoid", "retinoid x", "x receptor", "receptor alpha", "rxra .", "the heterodimer", "heterodimer was", "was initially", "initially identified", "identified as", "as a", "a complex", "complex regulating", "regulating the", "the ap2/fabp4", "ap2/fabp4 gene", "gene and", "and named", "named arf6", "tontonoz et", "al. 1994", "1994 .
the", ".
the pparg:rxra", "pparg:rxra heterodimer", "heterodimer binds", "binds a", "a recognition", "recognition sequence", "sequence that", "that consists", "consists of", "of two", "two hexanucleotide", "hexanucleotide motifs", "dr1 motifs", "separated by", "by 1", "1 nucleotide.", "nucleotide. binding", "binding occurs", "occurs even", "even in", "of ligands", "as fatty", "fatty acids", "that activate", "activate pparg.", "pparg. in", "of activating", "activating ligands", "the pparg:rxra", "pparg:rxra complex", "complex recruits", "recruits repressors", "repressors of", "transcription such", "as smrt/ncor2", "and hdac3", "tontonoz and", "and spiegelman", "spiegelman 2008", "2008 .
each", ".
each molecule", "molecule of", "of pparg", "pparg can", "can bind", "bind 2", "2 molecules", "molecules of", "activating ligands.", "ligands. although", "the identity", "identity of", "the endogenous", "endogenous ligands", "ligands of", "pparg is", "is unknown", "exogenous activators", "activators include", "include fatty", "acids and", "and the", "the thiazolidinedione", "thiazolidinedione class", "class of", "of antidiabetic", "antidiabetic drugs", "in berger", "berger et", "al. 2005", "heikkinen et", "lemberger et", "al. 1996", "1996 .", "most potent", "potent activators", "activators of", "pparg in", "in vitro", "vitro are", "are oxidized", "oxidized derivatives", "derivatives of", "of unsaturated", "unsaturated fatty", "fatty acids..", "acids.. upon", "upon binding", "binding activating", "ligands pparg", "pparg causes", "causes a", "a rearrangement", "rearrangement of", "of adjacent", "adjacent factors:", "factors: corepressors", "corepressors such", "smrt/ncor2 are", "are lost", "lost and", "and coactivators", "coactivators such", "as tif2", "and p300", "p300 are", "are recruited", "spiegelman .", ". pparg", "pparg also", "also binds", "binds directly", "directly to", "the trap220", "trap220 subunit", "subunit of", "the trap/mediator", "trap/mediator complex", "complex that", "that recruits", "recruits rna", "rna polymerase", "polymerase ii.", "ii. thus", "thus binding", "binding of", "activating ligand", "ligand by", "by pparg", "causes transcription", "transcription of", "pparg target", "target genes.
targets", "genes.
targets of", "pparg include", "include genes", "genes involved", "involved in", "in differentiation", "fatty acid", "acid transport", "carbohydrate metabolism", "pepck c", "and energy", "energy homeostasis", "leptin and", "and adiponectin", "perera et", "al. 2006", "2006 .
within", ".
within 10", "10 days", "days of", "of differentiation", "differentiation cebpb", "cebpd are", "are no", "no longer", "longer located", "located at", "promoter. instead", "instead cebpa", "cebpa is", "is present.", "present. ebf1", "pparg bind", "the cebpa", "cebpa promoter", "activate transcription", "the key", "key transcription", "factors in", "in adipogenesis.", "adipogenesis. a", "a current", "current hypothesis", "hypothesis posits", "posits a", "a self", "self reinforcing", "reinforcing loop", "loop that", "that maintains", "maintains pparg", "the differentiated", "differentiated state:", "state: pparg", "pparg activates", "activates cebpa", "and cebpa", "cebpa activates", "activates pparg.", "pparg. additionally", "additionally ebf1", "activates ebf1", "and ebf1", "ebf1 activates", "adipogenesis is the", "is the process", "the process of", "process of cell", "of cell differentiation", "cell differentiation by", "differentiation by which", "by which preadipocytes", "which preadipocytes become", "preadipocytes become adipocytes.", "become adipocytes. during", "adipocytes. during this", "during this process", "this process the", "process the preadipocytes", "the preadipocytes cease", "preadipocytes cease to", "cease to proliferate", "proliferate begin", "begin to accumulate", "to accumulate lipid", "accumulate lipid droplets", "lipid droplets and", "droplets and develop", "and develop morphologic", "develop morphologic and", "morphologic and biochemical", "and biochemical characteristics", "biochemical characteristics of", "characteristics of mature", "of mature adipocytes", "mature adipocytes such", "adipocytes such as", "such as hormone", "as hormone responsive", "hormone responsive lipogenenic", "responsive lipogenenic and", "lipogenenic and lipolytic", "and lipolytic programs.", "lipolytic programs. the", "programs. the most", "the most intensively", "most intensively studied", "intensively studied model", "studied model system", "model system for", "system for adipogenesis", "for adipogenesis is", "adipogenesis is differentiation", "is differentiation of", "differentiation of the", "of the mouse", "the mouse 3t3", "mouse 3t3 l1", "3t3 l1 preadipocyte", "l1 preadipocyte cell", "preadipocyte cell line", "cell line by", "line by an", "by an induction", "an induction cocktail", "induction cocktail of", "cocktail of containing", "of containing mitogens", "mitogens insulin/igf1", "glucocorticoid dexamethasone", "an inducer of", "inducer of camp", "camp ibmx", "and fetal serum", "serum cao", "cao et al.", "et al. 1991", "1991 reviewed", "reviewed in farmer", "in farmer 2006", "farmer 2006 .", "2006 . more", ". more recently", "more recently additional", "recently additional cellular", "additional cellular models", "cellular models have", "models have become", "have become available", "become available to", "available to study", "to study adipogenesis", "study adipogenesis that", "adipogenesis that involve", "that involve almost", "involve almost all", "almost all stages", "all stages of", "stages of development", "development reviewed", "reviewed in rosen", "in rosen and", "rosen and macdougald", "and macdougald 2006", "macdougald 2006 .", "2006 . in", ". in vivo", "in vivo knockout", "vivo knockout mice", "knockout mice lacking", "mice lacking putative", "lacking putative adipogenic", "putative adipogenic factors", "adipogenic factors have", "factors have also", "have also been", "also been extensively", "been extensively studied.", "extensively studied. human", "studied. human pathways", "human pathways are", "pathways are traditionally", "are traditionally inferred", "traditionally inferred from", "inferred from those", "from those discovered", "those discovered in", "discovered in mouse", "in mouse but", "mouse but are", "but are now", "are now beginning", "now beginning to", "beginning to be", "to be validated", "be validated in", "validated in cellular", "in cellular models", "cellular models derived", "models derived from", "derived from human", "from human adipose", "human adipose progenitors", "progenitors fischer", "fischer posovszky et", "posovszky et al.", "et al. 2008", "2008 wdziekonski", "wdziekonski et al.", "et al. 2011", "al. 2011 .
adipogenesis", "2011 .
adipogenesis is", ".
adipogenesis is controlled", "is controlled by", "controlled by a", "by a cascade", "a cascade of", "cascade of transcription", "of transcription factors", "factors yeh", "yeh et al.", "et al. 1995", "1995 reviewed", "2006 gesta", "gesta et al.", "et al. 2007", "al. 2007 .", "2007 . one", ". one of", "one of the", "of the first", "the first observable", "first observable events", "observable events during", "events during adipocyte", "during adipocyte differentiation", "adipocyte differentiation is", "differentiation is a", "is a transient", "a transient increase", "transient increase in", "increase in expression", "in expression of", "expression of the", "of the cebpb", "cebpb ccaat/enhancer", "ccaat/enhancer binding protein", "binding protein beta", "beta c/ebpb", "c/ebpb and", "cebpd c/ebpd", "c/ebpd transcription", "factors cao", "reviewed in lane", "in lane et", "lane et al.", "et al. 1999", "al. 1999 .", "1999 . this", ". this occurs", "this occurs prior", "occurs prior to", "prior to the", "to the accumulation", "the accumulation of", "accumulation of lipid", "of lipid droplets.", "lipid droplets. however", "however it", "it is the", "is the subsequent", "the subsequent inductions", "subsequent inductions of", "inductions of cebpa", "of cebpa and", "cebpa and pparg", "and pparg that", "pparg that are", "that are critical", "are critical for", "critical for morphological", "morphological biochemical", "biochemical and functional", "and functional adipocytes.
ectopic", "functional adipocytes.
ectopic expression", "adipocytes.
ectopic expression of", "expression of cebpb", "of cebpb alone", "cebpb alone is", "alone is capable", "is capable of", "capable of inducing", "of inducing substantial", "inducing substantial adipocyte", "substantial adipocyte differentiation", "adipocyte differentiation in", "differentiation in fibroblasts", "in fibroblasts while", "fibroblasts while cebpd", "while cebpd has", "cebpd has a", "has a minimal", "a minimal effect.", "minimal effect. cebpb", "effect. cebpb is", "cebpb is upregulated", "is upregulated in", "upregulated in response", "in response to", "response to intracellular", "to intracellular camp", "camp possibly", "possibly via pcreb", "pcreb and", "and serum mitogens", "mitogens possibly", "possibly via krox20", "via krox20 .", "krox20 . cebpd", ". cebpd is", "cebpd is upregulated", "response to glucocorticoids.", "to glucocorticoids. the", "glucocorticoids. the exact", "the exact mechanisms", "exact mechanisms that", "mechanisms that upregulate", "that upregulate the", "upregulate the cebps", "the cebps are", "cebps are not", "are not fully", "not fully known.
cebpb", "fully known.
cebpb and", "known.
cebpb and cebpd", "and cebpd act", "cebpd act directly", "act directly on", "directly on the", "on the peroxisome", "the peroxisome proliferator", "peroxisome proliferator activated", "proliferator activated receptor", "activated receptor gamma", "gamma pparg", "gene by binding", "by binding its", "binding its promoter", "its promoter and", "promoter and activating", "and activating transcription.", "activating transcription. cebpb", "transcription. cebpb and", "cebpb and cebpd", "and cebpd also", "cebpd also directly", "also directly activate", "directly activate the", "activate the ebf1", "the ebf1 gene", "and possibly other", "possibly other ebfs", "ebfs and", "klf5 jimenez", "jimenez et al.", "2007 oishi", "oishi 2005 .", "2005 . the", ". the ebf1", "the ebf1 and", "ebf1 and klf5", "and klf5 proteins", "proteins in", "in turn bind", "bind and", "and activate the", "activate the pparg", "the pparg promoter.", "pparg promoter. other", "promoter. other hormones", "hormones such", "such as insulin", "insulin affect", "affect pparg expression", "pparg expression and", "expression and other", "and other transcription", "other transcription factors", "factors such", "such as add1/srebp1c", "add1/srebp1c bind", "bind the pparg", "pparg promoter. this", "promoter. this is", "this is an", "is an area", "an area of", "area of ongoing", "of ongoing research.
during", "ongoing research.
during adipogenesis", "research.
during adipogenesis the", "adipogenesis the pparg", "the pparg gene", "pparg gene is", "gene is transcribed", "is transcribed to", "transcribed to yield", "to yield 2", "yield 2 variants.", "2 variants. the", "variants. the adipogenic", "the adipogenic variant", "adipogenic variant 2", "variant 2 mrna", "2 mrna encodes", "mrna encodes 30", "encodes 30 additional", "30 additional amino", "additional amino acids", "amino acids at", "acids at the", "at the n", "the n terminus", "n terminus compared", "terminus compared to", "compared to the", "to the widely", "the widely expressed", "widely expressed variant", "expressed variant 1", "variant 1 mrna.
pparg", "1 mrna.
pparg encodes", "mrna.
pparg encodes a", "encodes a type", "a type ii", "type ii nuclear", "ii nuclear hormone", "nuclear hormone receptor", "receptor remains", "remains in the", "in the nucleus", "the nucleus in", "nucleus in the", "in the absence", "the absence of", "absence of ligand", "ligand that", "that forms a", "forms a heterodimer", "a heterodimer with", "heterodimer with the", "with the retinoid", "the retinoid x", "retinoid x receptor", "x receptor alpha", "alpha rxra", "rxra . the", ". the heterodimer", "the heterodimer was", "heterodimer was initially", "was initially identified", "initially identified as", "identified as a", "as a complex", "a complex regulating", "complex regulating the", "regulating the ap2/fabp4", "the ap2/fabp4 gene", "ap2/fabp4 gene and", "gene and named", "and named arf6", "arf6 tontonoz", "tontonoz et al.", "et al. 1994", "al. 1994 .
the", "1994 .
the pparg:rxra", ".
the pparg:rxra heterodimer", "pparg:rxra heterodimer binds", "heterodimer binds a", "binds a recognition", "a recognition sequence", "recognition sequence that", "sequence that consists", "that consists of", "consists of two", "of two hexanucleotide", "two hexanucleotide motifs", "motifs dr1", "motifs separated", "separated by 1", "by 1 nucleotide.", "1 nucleotide. binding", "nucleotide. binding occurs", "binding occurs even", "occurs even in", "even in the", "absence of ligands", "ligands such", "such as fatty", "as fatty acids", "acids that", "that activate pparg.", "activate pparg. in", "pparg. in the", "absence of activating", "of activating ligands", "ligands the", "the pparg:rxra complex", "pparg:rxra complex recruits", "complex recruits repressors", "recruits repressors of", "repressors of transcription", "of transcription such", "transcription such as", "such as smrt/ncor2", "smrt/ncor2 ncor1", "ncor1 and", "hdac3 tontonoz", "tontonoz and spiegelman", "and spiegelman 2008", "spiegelman 2008 .
each", "2008 .
each molecule", ".
each molecule of", "molecule of pparg", "of pparg can", "pparg can bind", "can bind 2", "bind 2 molecules", "2 molecules of", "molecules of activating", "of activating ligands.", "activating ligands. although", "although the", "the identity of", "identity of the", "of the endogenous", "the endogenous ligands", "endogenous ligands of", "ligands of pparg", "of pparg is", "pparg is unknown", "unknown exogenous", "exogenous activators include", "activators include fatty", "include fatty acids", "fatty acids and", "acids and the", "and the thiazolidinedione", "the thiazolidinedione class", "thiazolidinedione class of", "class of antidiabetic", "of antidiabetic drugs", "drugs reviewed", "reviewed in berger", "in berger et", "berger et al.", "et al. 2005", "2005 heikkinen", "heikkinen et al.", "2007 lemberger", "lemberger et al.", "et al. 1996", "al. 1996 .", "1996 . the", ". the most", "the most potent", "most potent activators", "potent activators of", "activators of pparg", "of pparg in", "pparg in vitro", "in vitro are", "vitro are oxidized", "are oxidized derivatives", "oxidized derivatives of", "derivatives of unsaturated", "of unsaturated fatty", "unsaturated fatty acids..", "fatty acids.. upon", "acids.. upon binding", "upon binding activating", "binding activating ligands", "activating ligands pparg", "ligands pparg causes", "pparg causes a", "causes a rearrangement", "a rearrangement of", "rearrangement of adjacent", "of adjacent factors:", "adjacent factors: corepressors", "factors: corepressors such", "corepressors such as", "as smrt/ncor2 are", "smrt/ncor2 are lost", "are lost and", "lost and coactivators", "and coactivators such", "coactivators such as", "such as tif2", "tif2 prip", "prip cbp", "cbp and", "and p300 are", "p300 are recruited", "recruited tontonoz", "and spiegelman .", "spiegelman . pparg", ". pparg also", "pparg also binds", "also binds directly", "binds directly to", "directly to the", "to the trap220", "the trap220 subunit", "trap220 subunit of", "subunit of the", "of the trap/mediator", "the trap/mediator complex", "trap/mediator complex that", "complex that recruits", "that recruits rna", "recruits rna polymerase", "rna polymerase ii.", "polymerase ii. thus", "ii. thus binding", "thus binding of", "binding of activating", "of activating ligand", "activating ligand by", "ligand by pparg", "by pparg causes", "pparg causes transcription", "causes transcription of", "transcription of pparg", "of pparg target", "pparg target genes.
targets", "target genes.
targets of", "genes.
targets of pparg", "of pparg include", "pparg include genes", "include genes involved", "genes involved in", "involved in differentiation", "differentiation pgar/hfarp", "pgar/hfarp perilipin", "perilipin ap2/fabp4", "ap2/fabp4 cebpa", "fatty acid transport", "transport lpl", "lpl fat/cd36", "metabolism pepck", "c aqp7", "aqp7 gk", "gk glut4", "glut4 slc2a4", "and energy homeostasis", "homeostasis leptin", "leptin and adiponectin", "perera et al.", "et al. 2006", "al. 2006 .
within", "2006 .
within 10", ".
within 10 days", "10 days of", "days of differentiation", "of differentiation cebpb", "differentiation cebpb and", "and cebpd are", "cebpd are no", "are no longer", "no longer located", "longer located at", "located at the", "at the pparg", "pparg promoter. instead", "promoter. instead cebpa", "instead cebpa is", "cebpa is present.", "is present. ebf1", "present. ebf1 and", "ebf1 and pparg", "and pparg bind", "pparg bind the", "bind the cebpa", "the cebpa promoter", "cebpa promoter and", "promoter and activate", "and activate transcription", "activate transcription of", "transcription of cebpa", "cebpa one", "of the key", "the key transcription", "key transcription factors", "transcription factors in", "factors in adipogenesis.", "in adipogenesis. a", "adipogenesis. a current", "a current hypothesis", "current hypothesis posits", "hypothesis posits a", "posits a self", "a self reinforcing", "self reinforcing loop", "reinforcing loop that", "loop that maintains", "that maintains pparg", "maintains pparg expression", "expression and the", "and the differentiated", "the differentiated state:", "differentiated state: pparg", "state: pparg activates", "pparg activates cebpa", "activates cebpa and", "cebpa and cebpa", "and cebpa activates", "cebpa activates pparg.", "activates pparg. additionally", "pparg. additionally ebf1", "ebfs activates", "cebpa cebpa", "cebpa activates ebf1", "and ebf1 activates", "ebf1 activates pparg.", "adipogenesis is the process", "is the process of", "the process of cell", "process of cell differentiation", "of cell differentiation by", "cell differentiation by which", "differentiation by which preadipocytes", "by which preadipocytes become", "which preadipocytes become adipocytes.", "preadipocytes become adipocytes. during", "become adipocytes. during this", "adipocytes. during this process", "during this process the", "this process the preadipocytes", "process the preadipocytes cease", "the preadipocytes cease to", "preadipocytes cease to proliferate", "to proliferate begin", "proliferate begin to", "begin to accumulate lipid", "to accumulate lipid droplets", "accumulate lipid droplets and", "lipid droplets and develop", "droplets and develop morphologic", "and develop morphologic and", "develop morphologic and biochemical", "morphologic and biochemical characteristics", "and biochemical characteristics of", "biochemical characteristics of mature", "characteristics of mature adipocytes", "of mature adipocytes such", "mature adipocytes such as", "adipocytes such as hormone", "such as hormone responsive", "as hormone responsive lipogenenic", "hormone responsive lipogenenic and", "responsive lipogenenic and lipolytic", "lipogenenic and lipolytic programs.", "and lipolytic programs. the", "lipolytic programs. the most", "programs. the most intensively", "the most intensively studied", "most intensively studied model", "intensively studied model system", "studied model system for", "model system for adipogenesis", "system for adipogenesis is", "for adipogenesis is differentiation", "adipogenesis is differentiation of", "is differentiation of the", "differentiation of the mouse", "of the mouse 3t3", "the mouse 3t3 l1", "mouse 3t3 l1 preadipocyte", "3t3 l1 preadipocyte cell", "l1 preadipocyte cell line", "preadipocyte cell line by", "cell line by an", "line by an induction", "by an induction cocktail", "an induction cocktail of", "induction cocktail of containing", "cocktail of containing mitogens", "containing mitogens insulin/igf1", "insulin/igf1 glucocorticoid", "dexamethasone an", "an inducer of camp", "of camp ibmx", "ibmx and", "fetal serum cao", "serum cao et", "cao et al. 1991", "al. 1991 reviewed", "1991 reviewed in", "reviewed in farmer 2006", "in farmer 2006 .", "farmer 2006 . more", "2006 . more recently", ". more recently additional", "more recently additional cellular", "recently additional cellular models", "additional cellular models have", "cellular models have become", "models have become available", "have become available to", "become available to study", "available to study adipogenesis", "to study adipogenesis that", "study adipogenesis that involve", "adipogenesis that involve almost", "that involve almost all", "involve almost all stages", "almost all stages of", "all stages of development", "of development reviewed", "development reviewed in", "reviewed in rosen and", "in rosen and macdougald", "rosen and macdougald 2006", "and macdougald 2006 .", "macdougald 2006 . in", "2006 . in vivo", ". in vivo knockout", "in vivo knockout mice", "vivo knockout mice lacking", "knockout mice lacking putative", "mice lacking putative adipogenic", "lacking putative adipogenic factors", "putative adipogenic factors have", "adipogenic factors have also", "factors have also been", "have also been extensively", "also been extensively studied.", "been extensively studied. human", "extensively studied. human pathways", "studied. human pathways are", "human pathways are traditionally", "pathways are traditionally inferred", "are traditionally inferred from", "traditionally inferred from those", "inferred from those discovered", "from those discovered in", "those discovered in mouse", "discovered in mouse but", "in mouse but are", "mouse but are now", "but are now beginning", "are now beginning to", "now beginning to be", "beginning to be validated", "to be validated in", "be validated in cellular", "validated in cellular models", "in cellular models derived", "cellular models derived from", "models derived from human", "derived from human adipose", "from human adipose progenitors", "adipose progenitors fischer", "progenitors fischer posovszky", "fischer posovszky et al.", "posovszky et al. 2008", "al. 2008 wdziekonski", "2008 wdziekonski et", "wdziekonski et al. 2011", "et al. 2011 .
adipogenesis", "al. 2011 .
adipogenesis is", "2011 .
adipogenesis is controlled", ".
adipogenesis is controlled by", "is controlled by a", "controlled by a cascade", "by a cascade of", "a cascade of transcription", "cascade of transcription factors", "transcription factors yeh", "factors yeh et", "yeh et al. 1995", "al. 1995 reviewed", "1995 reviewed in", "farmer 2006 gesta", "2006 gesta et", "gesta et al. 2007", "et al. 2007 .", "al. 2007 . one", "2007 . one of", ". one of the", "one of the first", "of the first observable", "the first observable events", "first observable events during", "observable events during adipocyte", "events during adipocyte differentiation", "during adipocyte differentiation is", "adipocyte differentiation is a", "differentiation is a transient", "is a transient increase", "a transient increase in", "transient increase in expression", "increase in expression of", "in expression of the", "expression of the cebpb", "the cebpb ccaat/enhancer", "cebpb ccaat/enhancer binding", "ccaat/enhancer binding protein beta", "protein beta c/ebpb", "c/ebpb and cebpd", "and cebpd c/ebpd", "c/ebpd transcription factors", "transcription factors cao", "factors cao et", "reviewed in lane et", "in lane et al.", "lane et al. 1999", "et al. 1999 .", "al. 1999 . this", "1999 . this occurs", ". this occurs prior", "this occurs prior to", "occurs prior to the", "prior to the accumulation", "to the accumulation of", "the accumulation of lipid", "accumulation of lipid droplets.", "of lipid droplets. however", "droplets. however it", "however it is", "it is the subsequent", "is the subsequent inductions", "the subsequent inductions of", "subsequent inductions of cebpa", "inductions of cebpa and", "of cebpa and pparg", "cebpa and pparg that", "and pparg that are", "pparg that are critical", "that are critical for", "are critical for morphological", "for morphological biochemical", "morphological biochemical and", "biochemical and functional adipocytes.
ectopic", "and functional adipocytes.
ectopic expression", "functional adipocytes.
ectopic expression of", "adipocytes.
ectopic expression of cebpb", "expression of cebpb alone", "of cebpb alone is", "cebpb alone is capable", "alone is capable of", "is capable of inducing", "capable of inducing substantial", "of inducing substantial adipocyte", "inducing substantial adipocyte differentiation", "substantial adipocyte differentiation in", "adipocyte differentiation in fibroblasts", "differentiation in fibroblasts while", "in fibroblasts while cebpd", "fibroblasts while cebpd has", "while cebpd has a", "cebpd has a minimal", "has a minimal effect.", "a minimal effect. cebpb", "minimal effect. cebpb is", "effect. cebpb is upregulated", "cebpb is upregulated in", "is upregulated in response", "upregulated in response to", "in response to intracellular", "response to intracellular camp", "intracellular camp possibly", "camp possibly via", "via pcreb and", "pcreb and serum", "serum mitogens possibly", "mitogens possibly via", "possibly via krox20 .", "via krox20 . cebpd", "krox20 . cebpd is", ". cebpd is upregulated", "cebpd is upregulated in", "in response to glucocorticoids.", "response to glucocorticoids. the", "to glucocorticoids. the exact", "glucocorticoids. the exact mechanisms", "the exact mechanisms that", "exact mechanisms that upregulate", "mechanisms that upregulate the", "that upregulate the cebps", "upregulate the cebps are", "the cebps are not", "cebps are not fully", "are not fully known.
cebpb", "not fully known.
cebpb and", "fully known.
cebpb and cebpd", "known.
cebpb and cebpd act", "and cebpd act directly", "cebpd act directly on", "act directly on the", "directly on the peroxisome", "on the peroxisome proliferator", "the peroxisome proliferator activated", "peroxisome proliferator activated receptor", "proliferator activated receptor gamma", "receptor gamma pparg", "pparg gene by", "gene by binding its", "by binding its promoter", "binding its promoter and", "its promoter and activating", "promoter and activating transcription.", "and activating transcription. cebpb", "activating transcription. cebpb and", "transcription. cebpb and cebpd", "cebpb and cebpd also", "and cebpd also directly", "cebpd also directly activate", "also directly activate the", "directly activate the ebf1", "activate the ebf1 gene", "ebf1 gene and", "gene and possibly", "and possibly other ebfs", "other ebfs and", "ebfs and klf5", "and klf5 jimenez", "klf5 jimenez et", "jimenez et al. 2007", "al. 2007 oishi", "2007 oishi 2005", "oishi 2005 . the", "2005 . the ebf1", ". the ebf1 and", "the ebf1 and klf5", "ebf1 and klf5 proteins", "klf5 proteins in", "proteins in turn", "turn bind and", "bind and activate", "and activate the pparg", "activate the pparg promoter.", "the pparg promoter. other", "pparg promoter. other hormones", "other hormones such", "hormones such as", "as insulin affect", "insulin affect pparg", "affect pparg expression and", "pparg expression and other", "expression and other transcription", "and other transcription factors", "transcription factors such", "factors such as", "as add1/srebp1c bind", "add1/srebp1c bind the", "bind the pparg promoter.", "the pparg promoter. this", "pparg promoter. this is", "promoter. this is an", "this is an area", "is an area of", "an area of ongoing", "area of ongoing research.
during", "of ongoing research.
during adipogenesis", "ongoing research.
during adipogenesis the", "research.
during adipogenesis the pparg", "adipogenesis the pparg gene", "the pparg gene is", "pparg gene is transcribed", "gene is transcribed to", "is transcribed to yield", "transcribed to yield 2", "to yield 2 variants.", "yield 2 variants. the", "2 variants. the adipogenic", "variants. the adipogenic variant", "the adipogenic variant 2", "adipogenic variant 2 mrna", "variant 2 mrna encodes", "2 mrna encodes 30", "mrna encodes 30 additional", "encodes 30 additional amino", "30 additional amino acids", "additional amino acids at", "amino acids at the", "acids at the n", "at the n terminus", "the n terminus compared", "n terminus compared to", "terminus compared to the", "compared to the widely", "to the widely expressed", "the widely expressed variant", "widely expressed variant 1", "expressed variant 1 mrna.
pparg", "variant 1 mrna.
pparg encodes", "1 mrna.
pparg encodes a", "mrna.
pparg encodes a type", "encodes a type ii", "a type ii nuclear", "type ii nuclear hormone", "ii nuclear hormone receptor", "hormone receptor remains", "receptor remains in", "remains in the nucleus", "in the nucleus in", "the nucleus in the", "nucleus in the absence", "in the absence of", "the absence of ligand", "of ligand that", "ligand that forms", "that forms a heterodimer", "forms a heterodimer with", "a heterodimer with the", "heterodimer with the retinoid", "with the retinoid x", "the retinoid x receptor", "retinoid x receptor alpha", "receptor alpha rxra", "alpha rxra .", "rxra . the heterodimer", ". the heterodimer was", "the heterodimer was initially", "heterodimer was initially identified", "was initially identified as", "initially identified as a", "identified as a complex", "as a complex regulating", "a complex regulating the", "complex regulating the ap2/fabp4", "regulating the ap2/fabp4 gene", "the ap2/fabp4 gene and", "ap2/fabp4 gene and named", "gene and named arf6", "named arf6 tontonoz", "arf6 tontonoz et", "tontonoz et al. 1994", "et al. 1994 .
the", "al. 1994 .
the pparg:rxra", "1994 .
the pparg:rxra heterodimer", ".
the pparg:rxra heterodimer binds", "pparg:rxra heterodimer binds a", "heterodimer binds a recognition", "binds a recognition sequence", "a recognition sequence that", "recognition sequence that consists", "sequence that consists of", "that consists of two", "consists of two hexanucleotide", "of two hexanucleotide motifs", "hexanucleotide motifs dr1", "motifs dr1 motifs", "dr1 motifs separated", "motifs separated by", "separated by 1 nucleotide.", "by 1 nucleotide. binding", "1 nucleotide. binding occurs", "nucleotide. binding occurs even", "binding occurs even in", "occurs even in the", "even in the absence", "the absence of ligands", "of ligands such", "ligands such as", "such as fatty acids", "fatty acids that", "acids that activate", "that activate pparg. in", "activate pparg. in the", "pparg. in the absence", "the absence of activating", "absence of activating ligands", "activating ligands the", "ligands the pparg:rxra", "the pparg:rxra complex recruits", "pparg:rxra complex recruits repressors", "complex recruits repressors of", "recruits repressors of transcription", "repressors of transcription such", "of transcription such as", "transcription such as smrt/ncor2", "as smrt/ncor2 ncor1", "ncor1 and hdac3", "and hdac3 tontonoz", "hdac3 tontonoz and", "tontonoz and spiegelman 2008", "and spiegelman 2008 .
each", "spiegelman 2008 .
each molecule", "2008 .
each molecule of", ".
each molecule of pparg", "molecule of pparg can", "of pparg can bind", "pparg can bind 2", "can bind 2 molecules", "bind 2 molecules of", "2 molecules of activating", "molecules of activating ligands.", "of activating ligands. although", "ligands. although the", "although the identity", "the identity of the", "identity of the endogenous", "of the endogenous ligands", "the endogenous ligands of", "endogenous ligands of pparg", "ligands of pparg is", "of pparg is unknown", "is unknown exogenous", "unknown exogenous activators", "exogenous activators include fatty", "activators include fatty acids", "include fatty acids and", "fatty acids and the", "acids and the thiazolidinedione", "and the thiazolidinedione class", "the thiazolidinedione class of", "thiazolidinedione class of antidiabetic", "class of antidiabetic drugs", "antidiabetic drugs reviewed", "drugs reviewed in", "reviewed in berger et", "in berger et al.", "berger et al. 2005", "al. 2005 heikkinen", "2005 heikkinen et", "heikkinen et al. 2007", "al. 2007 lemberger", "2007 lemberger et", "lemberger et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the most", ". the most potent", "the most potent activators", "most potent activators of", "potent activators of pparg", "activators of pparg in", "of pparg in vitro", "pparg in vitro are", "in vitro are oxidized", "vitro are oxidized derivatives", "are oxidized derivatives of", "oxidized derivatives of unsaturated", "derivatives of unsaturated fatty", "of unsaturated fatty acids..", "unsaturated fatty acids.. upon", "fatty acids.. upon binding", "acids.. upon binding activating", "upon binding activating ligands", "binding activating ligands pparg", "activating ligands pparg causes", "ligands pparg causes a", "pparg causes a rearrangement", "causes a rearrangement of", "a rearrangement of adjacent", "rearrangement of adjacent factors:", "of adjacent factors: corepressors", "adjacent factors: corepressors such", "factors: corepressors such as", "corepressors such as smrt/ncor2", "such as smrt/ncor2 are", "as smrt/ncor2 are lost", "smrt/ncor2 are lost and", "are lost and coactivators", "lost and coactivators such", "and coactivators such as", "coactivators such as tif2", "as tif2 prip", "cbp and p300", "and p300 are recruited", "are recruited tontonoz", "recruited tontonoz and", "tontonoz and spiegelman .", "and spiegelman . pparg", "spiegelman . pparg also", ". pparg also binds", "pparg also binds directly", "also binds directly to", "binds directly to the", "directly to the trap220", "to the trap220 subunit", "the trap220 subunit of", "trap220 subunit of the", "subunit of the trap/mediator", "of the trap/mediator complex", "the trap/mediator complex that", "trap/mediator complex that recruits", "complex that recruits rna", "that recruits rna polymerase", "recruits rna polymerase ii.", "rna polymerase ii. thus", "polymerase ii. thus binding", "ii. thus binding of", "thus binding of activating", "binding of activating ligand", "of activating ligand by", "activating ligand by pparg", "ligand by pparg causes", "by pparg causes transcription", "pparg causes transcription of", "causes transcription of pparg", "transcription of pparg target", "of pparg target genes.
targets", "pparg target genes.
targets of", "target genes.
targets of pparg", "genes.
targets of pparg include", "of pparg include genes", "pparg include genes involved", "include genes involved in", "genes involved in differentiation", "in differentiation pgar/hfarp", "cebpa fatty", "acid transport lpl", "fat/cd36 carbohydrate", "carbohydrate metabolism pepck", "metabolism pepck c", "pepck c aqp7", "energy homeostasis leptin", "homeostasis leptin and", "adiponectin perera", "perera et al. 2006", "et al. 2006 .
within", "al. 2006 .
within 10", "2006 .
within 10 days", ".
within 10 days of", "10 days of differentiation", "days of differentiation cebpb", "of differentiation cebpb and", "differentiation cebpb and cebpd", "cebpb and cebpd are", "and cebpd are no", "cebpd are no longer", "are no longer located", "no longer located at", "longer located at the", "located at the pparg", "at the pparg promoter.", "the pparg promoter. instead", "pparg promoter. instead cebpa", "promoter. instead cebpa is", "instead cebpa is present.", "cebpa is present. ebf1", "is present. ebf1 and", "present. ebf1 and pparg", "ebf1 and pparg bind", "and pparg bind the", "pparg bind the cebpa", "bind the cebpa promoter", "the cebpa promoter and", "cebpa promoter and activate", "promoter and activate transcription", "and activate transcription of", "activate transcription of cebpa", "of cebpa one", "cebpa one of", "one of the key", "of the key transcription", "the key transcription factors", "key transcription factors in", "transcription factors in adipogenesis.", "factors in adipogenesis. a", "in adipogenesis. a current", "adipogenesis. a current hypothesis", "a current hypothesis posits", "current hypothesis posits a", "hypothesis posits a self", "posits a self reinforcing", "a self reinforcing loop", "self reinforcing loop that", "reinforcing loop that maintains", "loop that maintains pparg", "that maintains pparg expression", "maintains pparg expression and", "pparg expression and the", "expression and the differentiated", "and the differentiated state:", "the differentiated state: pparg", "differentiated state: pparg activates", "state: pparg activates cebpa", "pparg activates cebpa and", "activates cebpa and cebpa", "cebpa and cebpa activates", "and cebpa activates pparg.", "cebpa activates pparg. additionally", "activates pparg. additionally ebf1", "additionally ebf1 and", "ebf1 and possibly", "other ebfs activates", "ebfs activates cebpa", "activates cebpa cebpa", "cebpa cebpa activates", "activates ebf1 and", "ebf1 and ebf1", "and ebf1 activates pparg.", "adipogenesis is the process of", "is the process of cell", "the process of cell differentiation", "process of cell differentiation by", "of cell differentiation by which", "cell differentiation by which preadipocytes", "differentiation by which preadipocytes become", "by which preadipocytes become adipocytes.", "which preadipocytes become adipocytes. during", "preadipocytes become adipocytes. during this", "become adipocytes. during this process", "adipocytes. during this process the", "during this process the preadipocytes", "this process the preadipocytes cease", "process the preadipocytes cease to", "the preadipocytes cease to proliferate", "cease to proliferate begin", "to proliferate begin to", "proliferate begin to accumulate", "begin to accumulate lipid droplets", "to accumulate lipid droplets and", "accumulate lipid droplets and develop", "lipid droplets and develop morphologic", "droplets and develop morphologic and", "and develop morphologic and biochemical", "develop morphologic and biochemical characteristics", "morphologic and biochemical characteristics of", "and biochemical characteristics of mature", "biochemical characteristics of mature adipocytes", "characteristics of mature adipocytes such", "of mature adipocytes such as", "mature adipocytes such as hormone", "adipocytes such as hormone responsive", "such as hormone responsive lipogenenic", "as hormone responsive lipogenenic and", "hormone responsive lipogenenic and lipolytic", "responsive lipogenenic and lipolytic programs.", "lipogenenic and lipolytic programs. the", "and lipolytic programs. the most", "lipolytic programs. the most intensively", "programs. the most intensively studied", "the most intensively studied model", "most intensively studied model system", "intensively studied model system for", "studied model system for adipogenesis", "model system for adipogenesis is", "system for adipogenesis is differentiation", "for adipogenesis is differentiation of", "adipogenesis is differentiation of the", "is differentiation of the mouse", "differentiation of the mouse 3t3", "of the mouse 3t3 l1", "the mouse 3t3 l1 preadipocyte", "mouse 3t3 l1 preadipocyte cell", "3t3 l1 preadipocyte cell line", "l1 preadipocyte cell line by", "preadipocyte cell line by an", "cell line by an induction", "line by an induction cocktail", "by an induction cocktail of", "an induction cocktail of containing", "induction cocktail of containing mitogens", "of containing mitogens insulin/igf1", "dexamethasone an inducer", "inducer of camp ibmx", "ibmx and fetal", "and fetal serum cao", "fetal serum cao et", "serum cao et al.", "et al. 1991 reviewed", "al. 1991 reviewed in", "1991 reviewed in farmer", "reviewed in farmer 2006 .", "in farmer 2006 . more", "farmer 2006 . more recently", "2006 . more recently additional", ". more recently additional cellular", "more recently additional cellular models", "recently additional cellular models have", "additional cellular models have become", "cellular models have become available", "models have become available to", "have become available to study", "become available to study adipogenesis", "available to study adipogenesis that", "to study adipogenesis that involve", "study adipogenesis that involve almost", "adipogenesis that involve almost all", "that involve almost all stages", "involve almost all stages of", "almost all stages of development", "stages of development reviewed", "of development reviewed in", "development reviewed in rosen", "reviewed in rosen and macdougald", "in rosen and macdougald 2006", "rosen and macdougald 2006 .", "and macdougald 2006 . in", "macdougald 2006 . in vivo", "2006 . in vivo knockout", ". in vivo knockout mice", "in vivo knockout mice lacking", "vivo knockout mice lacking putative", "knockout mice lacking putative adipogenic", "mice lacking putative adipogenic factors", "lacking putative adipogenic factors have", "putative adipogenic factors have also", "adipogenic factors have also been", "factors have also been extensively", "have also been extensively studied.", "also been extensively studied. human", "been extensively studied. human pathways", "extensively studied. human pathways are", "studied. human pathways are traditionally", "human pathways are traditionally inferred", "pathways are traditionally inferred from", "are traditionally inferred from those", "traditionally inferred from those discovered", "inferred from those discovered in", "from those discovered in mouse", "those discovered in mouse but", "discovered in mouse but are", "in mouse but are now", "mouse but are now beginning", "but are now beginning to", "are now beginning to be", "now beginning to be validated", "beginning to be validated in", "to be validated in cellular", "be validated in cellular models", "validated in cellular models derived", "in cellular models derived from", "cellular models derived from human", "models derived from human adipose", "derived from human adipose progenitors", "human adipose progenitors fischer", "adipose progenitors fischer posovszky", "progenitors fischer posovszky et", "fischer posovszky et al. 2008", "et al. 2008 wdziekonski", "al. 2008 wdziekonski et", "2008 wdziekonski et al.", "wdziekonski et al. 2011 .
adipogenesis", "et al. 2011 .
adipogenesis is", "al. 2011 .
adipogenesis is controlled", "2011 .
adipogenesis is controlled by", ".
adipogenesis is controlled by a", "is controlled by a cascade", "controlled by a cascade of", "by a cascade of transcription", "a cascade of transcription factors", "of transcription factors yeh", "transcription factors yeh et", "factors yeh et al.", "et al. 1995 reviewed", "al. 1995 reviewed in", "1995 reviewed in farmer", "in farmer 2006 gesta", "farmer 2006 gesta et", "2006 gesta et al.", "gesta et al. 2007 .", "et al. 2007 . one", "al. 2007 . one of", "2007 . one of the", ". one of the first", "one of the first observable", "of the first observable events", "the first observable events during", "first observable events during adipocyte", "observable events during adipocyte differentiation", "events during adipocyte differentiation is", "during adipocyte differentiation is a", "adipocyte differentiation is a transient", "differentiation is a transient increase", "is a transient increase in", "a transient increase in expression", "transient increase in expression of", "increase in expression of the", "in expression of the cebpb", "of the cebpb ccaat/enhancer", "the cebpb ccaat/enhancer binding", "cebpb ccaat/enhancer binding protein", "binding protein beta c/ebpb", "beta c/ebpb and", "cebpd c/ebpd transcription", "transcription factors cao et", "factors cao et al.", "1991 reviewed in lane", "reviewed in lane et al.", "in lane et al. 1999", "lane et al. 1999 .", "et al. 1999 . this", "al. 1999 . this occurs", "1999 . this occurs prior", ". this occurs prior to", "this occurs prior to the", "occurs prior to the accumulation", "prior to the accumulation of", "to the accumulation of lipid", "the accumulation of lipid droplets.", "accumulation of lipid droplets. however", "lipid droplets. however it", "droplets. however it is", "however it is the", "it is the subsequent inductions", "is the subsequent inductions of", "the subsequent inductions of cebpa", "subsequent inductions of cebpa and", "inductions of cebpa and pparg", "of cebpa and pparg that", "cebpa and pparg that are", "and pparg that are critical", "pparg that are critical for", "that are critical for morphological", "critical for morphological biochemical", "for morphological biochemical and", "morphological biochemical and functional", "biochemical and functional adipocytes.
ectopic expression", "and functional adipocytes.
ectopic expression of", "functional adipocytes.
ectopic expression of cebpb", "adipocytes.
ectopic expression of cebpb alone", "expression of cebpb alone is", "of cebpb alone is capable", "cebpb alone is capable of", "alone is capable of inducing", "is capable of inducing substantial", "capable of inducing substantial adipocyte", "of inducing substantial adipocyte differentiation", "inducing substantial adipocyte differentiation in", "substantial adipocyte differentiation in fibroblasts", "adipocyte differentiation in fibroblasts while", "differentiation in fibroblasts while cebpd", "in fibroblasts while cebpd has", "fibroblasts while cebpd has a", "while cebpd has a minimal", "cebpd has a minimal effect.", "has a minimal effect. cebpb", "a minimal effect. cebpb is", "minimal effect. cebpb is upregulated", "effect. cebpb is upregulated in", "cebpb is upregulated in response", "is upregulated in response to", "upregulated in response to intracellular", "in response to intracellular camp", "to intracellular camp possibly", "intracellular camp possibly via", "camp possibly via pcreb", "possibly via pcreb and", "via pcreb and serum", "pcreb and serum mitogens", "and serum mitogens possibly", "serum mitogens possibly via", "mitogens possibly via krox20", "possibly via krox20 . cebpd", "via krox20 . cebpd is", "krox20 . cebpd is upregulated", ". cebpd is upregulated in", "cebpd is upregulated in response", "upregulated in response to glucocorticoids.", "in response to glucocorticoids. the", "response to glucocorticoids. the exact", "to glucocorticoids. the exact mechanisms", "glucocorticoids. the exact mechanisms that", "the exact mechanisms that upregulate", "exact mechanisms that upregulate the", "mechanisms that upregulate the cebps", "that upregulate the cebps are", "upregulate the cebps are not", "the cebps are not fully", "cebps are not fully known.
cebpb", "are not fully known.
cebpb and", "not fully known.
cebpb and cebpd", "fully known.
cebpb and cebpd act", "known.
cebpb and cebpd act directly", "and cebpd act directly on", "cebpd act directly on the", "act directly on the peroxisome", "directly on the peroxisome proliferator", "on the peroxisome proliferator activated", "the peroxisome proliferator activated receptor", "peroxisome proliferator activated receptor gamma", "activated receptor gamma pparg", "gamma pparg gene", "pparg gene by binding", "gene by binding its promoter", "by binding its promoter and", "binding its promoter and activating", "its promoter and activating transcription.", "promoter and activating transcription. cebpb", "and activating transcription. cebpb and", "activating transcription. cebpb and cebpd", "transcription. cebpb and cebpd also", "cebpb and cebpd also directly", "and cebpd also directly activate", "cebpd also directly activate the", "also directly activate the ebf1", "directly activate the ebf1 gene", "the ebf1 gene and", "ebf1 gene and possibly", "gene and possibly other", "possibly other ebfs and", "other ebfs and klf5", "and klf5 jimenez et", "klf5 jimenez et al.", "et al. 2007 oishi", "al. 2007 oishi 2005", "2007 oishi 2005 .", "oishi 2005 . the ebf1", "2005 . the ebf1 and", ". the ebf1 and klf5", "the ebf1 and klf5 proteins", "and klf5 proteins in", "klf5 proteins in turn", "proteins in turn bind", "in turn bind and", "turn bind and activate", "bind and activate the", "and activate the pparg promoter.", "activate the pparg promoter. other", "the pparg promoter. other hormones", "promoter. other hormones such", "other hormones such as", "hormones such as insulin", "such as insulin affect", "as insulin affect pparg", "insulin affect pparg expression", "affect pparg expression and other", "pparg expression and other transcription", "expression and other transcription factors", "other transcription factors such", "transcription factors such as", "factors such as add1/srebp1c", "such as add1/srebp1c bind", "as add1/srebp1c bind the", "add1/srebp1c bind the pparg", "bind the pparg promoter. this", "the pparg promoter. this is", "pparg promoter. this is an", "promoter. this is an area", "this is an area of", "is an area of ongoing", "an area of ongoing research.
during", "area of ongoing research.
during adipogenesis", "of ongoing research.
during adipogenesis the", "ongoing research.
during adipogenesis the pparg", "research.
during adipogenesis the pparg gene", "adipogenesis the pparg gene is", "the pparg gene is transcribed", "pparg gene is transcribed to", "gene is transcribed to yield", "is transcribed to yield 2", "transcribed to yield 2 variants.", "to yield 2 variants. the", "yield 2 variants. the adipogenic", "2 variants. the adipogenic variant", "variants. the adipogenic variant 2", "the adipogenic variant 2 mrna", "adipogenic variant 2 mrna encodes", "variant 2 mrna encodes 30", "2 mrna encodes 30 additional", "mrna encodes 30 additional amino", "encodes 30 additional amino acids", "30 additional amino acids at", "additional amino acids at the", "amino acids at the n", "acids at the n terminus", "at the n terminus compared", "the n terminus compared to", "n terminus compared to the", "terminus compared to the widely", "compared to the widely expressed", "to the widely expressed variant", "the widely expressed variant 1", "widely expressed variant 1 mrna.
pparg", "expressed variant 1 mrna.
pparg encodes", "variant 1 mrna.
pparg encodes a", "1 mrna.
pparg encodes a type", "mrna.
pparg encodes a type ii", "encodes a type ii nuclear", "a type ii nuclear hormone", "type ii nuclear hormone receptor", "nuclear hormone receptor remains", "hormone receptor remains in", "receptor remains in the", "remains in the nucleus in", "in the nucleus in the", "the nucleus in the absence", "nucleus in the absence of", "in the absence of ligand", "absence of ligand that", "of ligand that forms", "ligand that forms a", "that forms a heterodimer with", "forms a heterodimer with the", "a heterodimer with the retinoid", "heterodimer with the retinoid x", "with the retinoid x receptor", "the retinoid x receptor alpha", "x receptor alpha rxra", "receptor alpha rxra .", "alpha rxra . the", "rxra . the heterodimer was", ". the heterodimer was initially", "the heterodimer was initially identified", "heterodimer was initially identified as", "was initially identified as a", "initially identified as a complex", "identified as a complex regulating", "as a complex regulating the", "a complex regulating the ap2/fabp4", "complex regulating the ap2/fabp4 gene", "regulating the ap2/fabp4 gene and", "the ap2/fabp4 gene and named", "ap2/fabp4 gene and named arf6", "and named arf6 tontonoz", "named arf6 tontonoz et", "arf6 tontonoz et al.", "tontonoz et al. 1994 .
the", "et al. 1994 .
the pparg:rxra", "al. 1994 .
the pparg:rxra heterodimer", "1994 .
the pparg:rxra heterodimer binds", ".
the pparg:rxra heterodimer binds a", "pparg:rxra heterodimer binds a recognition", "heterodimer binds a recognition sequence", "binds a recognition sequence that", "a recognition sequence that consists", "recognition sequence that consists of", "sequence that consists of two", "that consists of two hexanucleotide", "consists of two hexanucleotide motifs", "two hexanucleotide motifs dr1", "hexanucleotide motifs dr1 motifs", "dr1 motifs separated by", "motifs separated by 1", "separated by 1 nucleotide. binding", "by 1 nucleotide. binding occurs", "1 nucleotide. binding occurs even", "nucleotide. binding occurs even in", "binding occurs even in the", "occurs even in the absence", "even in the absence of", "in the absence of ligands", "absence of ligands such", "of ligands such as", "ligands such as fatty", "as fatty acids that", "fatty acids that activate", "acids that activate pparg.", "that activate pparg. in the", "activate pparg. in the absence", "pparg. in the absence of", "in the absence of activating", "the absence of activating ligands", "of activating ligands the", "activating ligands the pparg:rxra", "ligands the pparg:rxra complex", "the pparg:rxra complex recruits repressors", "pparg:rxra complex recruits repressors of", "complex recruits repressors of transcription", "recruits repressors of transcription such", "repressors of transcription such as", "of transcription such as smrt/ncor2", "such as smrt/ncor2 ncor1", "smrt/ncor2 ncor1 and", "and hdac3 tontonoz and", "hdac3 tontonoz and spiegelman", "tontonoz and spiegelman 2008 .
each", "and spiegelman 2008 .
each molecule", "spiegelman 2008 .
each molecule of", "2008 .
each molecule of pparg", ".
each molecule of pparg can", "molecule of pparg can bind", "of pparg can bind 2", "pparg can bind 2 molecules", "can bind 2 molecules of", "bind 2 molecules of activating", "2 molecules of activating ligands.", "molecules of activating ligands. although", "activating ligands. although the", "ligands. although the identity", "although the identity of", "the identity of the endogenous", "identity of the endogenous ligands", "of the endogenous ligands of", "the endogenous ligands of pparg", "endogenous ligands of pparg is", "ligands of pparg is unknown", "pparg is unknown exogenous", "is unknown exogenous activators", "unknown exogenous activators include", "exogenous activators include fatty acids", "activators include fatty acids and", "include fatty acids and the", "fatty acids and the thiazolidinedione", "acids and the thiazolidinedione class", "and the thiazolidinedione class of", "the thiazolidinedione class of antidiabetic", "thiazolidinedione class of antidiabetic drugs", "of antidiabetic drugs reviewed", "antidiabetic drugs reviewed in", "drugs reviewed in berger", "reviewed in berger et al.", "in berger et al. 2005", "et al. 2005 heikkinen", "al. 2005 heikkinen et", "2005 heikkinen et al.", "et al. 2007 lemberger", "al. 2007 lemberger et", "2007 lemberger et al.", "lemberger et al. 1996 .", "et al. 1996 . the", "al. 1996 . the most", "1996 . the most potent", ". the most potent activators", "the most potent activators of", "most potent activators of pparg", "potent activators of pparg in", "activators of pparg in vitro", "of pparg in vitro are", "pparg in vitro are oxidized", "in vitro are oxidized derivatives", "vitro are oxidized derivatives of", "are oxidized derivatives of unsaturated", "oxidized derivatives of unsaturated fatty", "derivatives of unsaturated fatty acids..", "of unsaturated fatty acids.. upon", "unsaturated fatty acids.. upon binding", "fatty acids.. upon binding activating", "acids.. upon binding activating ligands", "upon binding activating ligands pparg", "binding activating ligands pparg causes", "activating ligands pparg causes a", "ligands pparg causes a rearrangement", "pparg causes a rearrangement of", "causes a rearrangement of adjacent", "a rearrangement of adjacent factors:", "rearrangement of adjacent factors: corepressors", "of adjacent factors: corepressors such", "adjacent factors: corepressors such as", "factors: corepressors such as smrt/ncor2", "corepressors such as smrt/ncor2 are", "such as smrt/ncor2 are lost", "as smrt/ncor2 are lost and", "smrt/ncor2 are lost and coactivators", "are lost and coactivators such", "lost and coactivators such as", "and coactivators such as tif2", "such as tif2 prip", "tif2 prip cbp", "prip cbp and", "cbp and p300 are", "p300 are recruited tontonoz", "are recruited tontonoz and", "recruited tontonoz and spiegelman", "tontonoz and spiegelman . pparg", "and spiegelman . pparg also", "spiegelman . pparg also binds", ". pparg also binds directly", "pparg also binds directly to", "also binds directly to the", "binds directly to the trap220", "directly to the trap220 subunit", "to the trap220 subunit of", "the trap220 subunit of the", "trap220 subunit of the trap/mediator", "subunit of the trap/mediator complex", "of the trap/mediator complex that", "the trap/mediator complex that recruits", "trap/mediator complex that recruits rna", "complex that recruits rna polymerase", "that recruits rna polymerase ii.", "recruits rna polymerase ii. thus", "rna polymerase ii. thus binding", "polymerase ii. thus binding of", "ii. thus binding of activating", "thus binding of activating ligand", "binding of activating ligand by", "of activating ligand by pparg", "activating ligand by pparg causes", "ligand by pparg causes transcription", "by pparg causes transcription of", "pparg causes transcription of pparg", "causes transcription of pparg target", "transcription of pparg target genes.
targets", "of pparg target genes.
targets of", "pparg target genes.
targets of pparg", "target genes.
targets of pparg include", "genes.
targets of pparg include genes", "of pparg include genes involved", "pparg include genes involved in", "include genes involved in differentiation", "involved in differentiation pgar/hfarp", "differentiation pgar/hfarp perilipin", "pgar/hfarp perilipin ap2/fabp4", "perilipin ap2/fabp4 cebpa", "cebpa fatty acid", "fatty acid transport lpl", "transport lpl fat/cd36", "fat/cd36 carbohydrate metabolism", "carbohydrate metabolism pepck c", "c aqp7 gk", "aqp7 gk glut4", "gk glut4 slc2a4", "slc2a4 and", "and energy homeostasis leptin", "energy homeostasis leptin and", "homeostasis leptin and adiponectin", "and adiponectin perera", "adiponectin perera et", "perera et al. 2006 .
within", "et al. 2006 .
within 10", "al. 2006 .
within 10 days", "2006 .
within 10 days of", ".
within 10 days of differentiation", "10 days of differentiation cebpb", "days of differentiation cebpb and", "of differentiation cebpb and cebpd", "differentiation cebpb and cebpd are", "cebpb and cebpd are no", "and cebpd are no longer", "cebpd are no longer located", "are no longer located at", "no longer located at the", "longer located at the pparg", "located at the pparg promoter.", "at the pparg promoter. instead", "the pparg promoter. instead cebpa", "pparg promoter. instead cebpa is", "promoter. instead cebpa is present.", "instead cebpa is present. ebf1", "cebpa is present. ebf1 and", "is present. ebf1 and pparg", "present. ebf1 and pparg bind", "ebf1 and pparg bind the", "and pparg bind the cebpa", "pparg bind the cebpa promoter", "bind the cebpa promoter and", "the cebpa promoter and activate", "cebpa promoter and activate transcription", "promoter and activate transcription of", "and activate transcription of cebpa", "transcription of cebpa one", "of cebpa one of", "cebpa one of the", "one of the key transcription", "of the key transcription factors", "the key transcription factors in", "key transcription factors in adipogenesis.", "transcription factors in adipogenesis. a", "factors in adipogenesis. a current", "in adipogenesis. a current hypothesis", "adipogenesis. a current hypothesis posits", "a current hypothesis posits a", "current hypothesis posits a self", "hypothesis posits a self reinforcing", "posits a self reinforcing loop", "a self reinforcing loop that", "self reinforcing loop that maintains", "reinforcing loop that maintains pparg", "loop that maintains pparg expression", "that maintains pparg expression and", "maintains pparg expression and the", "pparg expression and the differentiated", "expression and the differentiated state:", "and the differentiated state: pparg", "the differentiated state: pparg activates", "differentiated state: pparg activates cebpa", "state: pparg activates cebpa and", "pparg activates cebpa and cebpa", "activates cebpa and cebpa activates", "cebpa and cebpa activates pparg.", "and cebpa activates pparg. additionally", "cebpa activates pparg. additionally ebf1", "pparg. additionally ebf1 and", "additionally ebf1 and possibly", "ebf1 and possibly other", "possibly other ebfs activates", "other ebfs activates cebpa", "activates cebpa cebpa activates", "cebpa cebpa activates ebf1", "cebpa activates ebf1 and", "activates ebf1 and ebf1", "ebf1 and ebf1 activates" ] }, { "record_id": "GLY_000594_1_302", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "381426", "r hsa", "hsa 381426", "r hsa 381426" ] }, { "record_id": "GLY_000594_1_302", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of insulin", "insulin like", "like growth", "growth factor", "transport and", "and uptake", "uptake by", "by insulin", "factor binding", "binding proteins", "regulation of insulin", "of insulin like", "insulin like growth", "like growth factor", "factor igf", "igf transport", "transport and uptake", "and uptake by", "uptake by insulin", "by insulin like", "growth factor binding", "factor binding proteins", "proteins igfbps", "regulation of insulin like", "of insulin like growth", "insulin like growth factor", "growth factor igf", "igf transport and", "transport and uptake by", "and uptake by insulin", "uptake by insulin like", "by insulin like growth", "like growth factor binding", "growth factor binding proteins", "binding proteins igfbps", "regulation of insulin like growth", "of insulin like growth factor", "like growth factor igf", "factor igf transport", "igf transport and uptake", "transport and uptake by insulin", "and uptake by insulin like", "uptake by insulin like growth", "by insulin like growth factor", "insulin like growth factor binding", "like growth factor binding proteins", "factor binding proteins igfbps", "the family", "family of", "share 50%", "50% amino", "amino acid", "acid identity", "identity with", "with conserved", "conserved n", "n terminal", "terminal and", "and c", "c terminal", "terminal regions", "regions responsible", "responsible for", "for binding", "binding insulin", "growth factors", "factors i", "i and", "and ii", "igf i", "and igf", "igf ii", "ii .", ". most", "most circulating", "circulating igfs", "igfs are", "are in", "in complexes", "complexes with", "with igfbps", "which are", "are believed", "believed to", "to increase", "increase the", "the residence", "residence of", "of igfs", "igfs in", "in the", "the body", "modulate availability", "availability of", "igfs to", "to target", "target receptors", "receptors for", "for igfs", "reduce insulin", "like effects", "effects of", "and act", "act as", "as signaling", "signaling molecules", "molecules independently", "independently of", "of igfs.", "igfs. about", "about 75%", "75% of", "of circulating", "in 1500", "1500 220", "220 kda", "kda complexes", "with igfbp3", "igfbp3 and", "and als.", "als. such", "such complexes", "complexes are", "are too", "too large", "large to", "to pass", "pass the", "the endothelial", "endothelial barrier.", "barrier. the", "the remaining", "remaining 20", "20 25%", "25% of", "are bound", "bound to", "to other", "other igfbps", "igfbps in", "in 40", "40 50", "50 kda", "kda complexes.", "complexes. igfs", "are released", "released from", "from igf:igfbp", "igf:igfbp complexes", "complexes by", "by proteolysis", "proteolysis of", "of the", "the igfbp.", "igfbp. igfs", "igfs become", "become active", "active after", "after release", "however igfs", "igfs may", "may also", "also have", "have activity", "activity when", "when still", "still bound", "to some", "some igfbps.", "igfbps. igfbp1", "igfbp1 is", "is enriched", "enriched in", "in amniotic", "amniotic fluid", "fluid and", "and is", "is produced", "produced in", "the liver", "liver under", "under control", "control of", "insulin suppresses", "suppresses production", "production .", ". igfbp1", "igfbp1 binding", "binding stimulates", "stimulates igf", "igf function.", "function. it", "it is", "is unknown", "unknown which", "which if", "if any", "any protease", "protease degrades", "degrades igfbp1.", "igfbp1. igfbp2", "igfbp2 is", "in cerebrospinal", "cerebrospinal fluid", "its binding", "binding inhibits", "inhibits igf", "function. igfbp2", "is not", "not significantly", "significantly degraded", "degraded in", "in circulation.", "circulation. igfb3", "which binds", "binds most", "most igf", "igf in", "body is", "in follicular", "follicular fluid", "and found", "found in", "in many", "many other", "other tissues.", "tissues. igfbp", "igfbp 3", "3 may", "may be", "be cleaved", "cleaved by", "by plasmin", "prostate specific", "specific antigen", "matrix metalloprotease", "metalloprotease 1", "and matrix", "metalloprotease 2", "mmp2 .", ". igfbp3", "igfbp3 also", "also binds", "binds extracellular", "extracellular matrix", "matrix and", "and binding", "binding lowers", "lowers its", "its affinity", "affinity for", "for igfs.", "igfs. igfbp3", "igfbp3 binding", "stimulates the", "the effects", "igfs. igfbp4", "igfbp4 acts", "acts to", "to inhibit", "inhibit igf", "igf function", "function and", "is cleaved", "by pregnancy", "pregnancy associated", "associated plasma", "plasma protein", "protein a", "to release", "release igf.", "igf. igfbp5", "igfbp5 is", "in bone", "bone matrix", "function. igfbp5", "protein a2", "complement c1s", "c1s from", "from smooth", "smooth muscle", "and thrombin.", "thrombin. only", "only the", "the cleavage", "cleavage site", "site for", "for pappa2", "pappa2 is", "is known.", "known. igfbp6", "igfbp6 is", "cerebrospinal fluid.", "fluid. it", "degrades igfbp6.", "the family of", "family of insulin", "igfbps share", "share 50% amino", "50% amino acid", "amino acid identity", "acid identity with", "identity with conserved", "with conserved n", "conserved n terminal", "n terminal and", "terminal and c", "and c terminal", "c terminal regions", "terminal regions responsible", "regions responsible for", "responsible for binding", "for binding insulin", "binding insulin like", "like growth factors", "growth factors i", "factors i and", "i and ii", "ii igf", "igf i and", "i and igf", "and igf ii", "igf ii .", "ii . most", ". most circulating", "most circulating igfs", "circulating igfs are", "igfs are in", "are in complexes", "in complexes with", "complexes with igfbps", "igfbps which", "which are believed", "are believed to", "believed to increase", "to increase the", "increase the residence", "the residence of", "residence of igfs", "of igfs in", "igfs in the", "in the body", "body modulate", "modulate availability of", "availability of igfs", "of igfs to", "igfs to target", "to target receptors", "target receptors for", "receptors for igfs", "igfs reduce", "reduce insulin like", "insulin like effects", "like effects of", "effects of igfs", "igfs and", "and act as", "act as signaling", "as signaling molecules", "signaling molecules independently", "molecules independently of", "independently of igfs.", "of igfs. about", "igfs. about 75%", "about 75% of", "75% of circulating", "of circulating igfs", "are in 1500", "in 1500 220", "1500 220 kda", "220 kda complexes", "kda complexes with", "complexes with igfbp3", "with igfbp3 and", "igfbp3 and als.", "and als. such", "als. such complexes", "such complexes are", "complexes are too", "are too large", "too large to", "large to pass", "to pass the", "pass the endothelial", "the endothelial barrier.", "endothelial barrier. the", "barrier. the remaining", "the remaining 20", "remaining 20 25%", "20 25% of", "25% of igfs", "of igfs are", "igfs are bound", "are bound to", "bound to other", "to other igfbps", "other igfbps in", "igfbps in 40", "in 40 50", "40 50 kda", "50 kda complexes.", "kda complexes. igfs", "complexes. igfs are", "igfs are released", "are released from", "released from igf:igfbp", "from igf:igfbp complexes", "igf:igfbp complexes by", "complexes by proteolysis", "by proteolysis of", "proteolysis of the", "of the igfbp.", "the igfbp. igfs", "igfbp. igfs become", "igfs become active", "become active after", "active after release", "release however", "however igfs may", "igfs may also", "may also have", "also have activity", "have activity when", "activity when still", "when still bound", "still bound to", "bound to some", "to some igfbps.", "some igfbps. igfbp1", "igfbps. igfbp1 is", "igfbp1 is enriched", "is enriched in", "enriched in amniotic", "in amniotic fluid", "amniotic fluid and", "fluid and is", "and is produced", "is produced in", "produced in the", "in the liver", "the liver under", "liver under control", "under control of", "control of insulin", "insulin insulin", "insulin suppresses production", "suppresses production .", "production . igfbp1", ". igfbp1 binding", "igfbp1 binding stimulates", "binding stimulates igf", "stimulates igf function.", "igf function. it", "function. it is", "it is unknown", "is unknown which", "unknown which if", "which if any", "if any protease", "any protease degrades", "protease degrades igfbp1.", "degrades igfbp1. igfbp2", "igfbp1. igfbp2 is", "igfbp2 is enriched", "enriched in cerebrospinal", "in cerebrospinal fluid", "fluid its", "its binding inhibits", "binding inhibits igf", "inhibits igf function.", "igf function. igfbp2", "function. igfbp2 is", "igfbp2 is not", "is not significantly", "not significantly degraded", "significantly degraded in", "degraded in circulation.", "in circulation. igfb3", "igfb3 which", "which binds most", "binds most igf", "most igf in", "igf in the", "the body is", "body is enriched", "enriched in follicular", "in follicular fluid", "follicular fluid and", "fluid and found", "and found in", "found in many", "in many other", "many other tissues.", "other tissues. igfbp", "tissues. igfbp 3", "igfbp 3 may", "3 may be", "may be cleaved", "be cleaved by", "cleaved by plasmin", "plasmin thrombin", "thrombin prostate", "prostate specific antigen", "antigen psa", "psa klk3", "matrix metalloprotease 1", "1 mmp1", "and matrix metalloprotease", "matrix metalloprotease 2", "2 mmp2", "mmp2 . igfbp3", ". igfbp3 also", "igfbp3 also binds", "also binds extracellular", "binds extracellular matrix", "extracellular matrix and", "matrix and binding", "and binding lowers", "binding lowers its", "lowers its affinity", "its affinity for", "affinity for igfs.", "for igfs. igfbp3", "igfs. igfbp3 binding", "igfbp3 binding stimulates", "binding stimulates the", "stimulates the effects", "the effects of", "effects of igfs.", "of igfs. igfbp4", "igfs. igfbp4 acts", "igfbp4 acts to", "acts to inhibit", "to inhibit igf", "inhibit igf function", "igf function and", "function and is", "and is cleaved", "is cleaved by", "cleaved by pregnancy", "by pregnancy associated", "pregnancy associated plasma", "associated plasma protein", "plasma protein a", "a pappa", "pappa to", "to release igf.", "release igf. igfbp5", "igf. igfbp5 is", "igfbp5 is enriched", "enriched in bone", "in bone matrix", "matrix its", "its binding stimulates", "igf function. igfbp5", "function. igfbp5 is", "igfbp5 is cleaved", "plasma protein a2", "a2 pappa2", "adam9 complement", "complement c1s from", "c1s from smooth", "from smooth muscle", "muscle and", "and thrombin. only", "thrombin. only the", "only the cleavage", "the cleavage site", "cleavage site for", "site for pappa2", "for pappa2 is", "pappa2 is known.", "is known. igfbp6", "known. igfbp6 is", "igfbp6 is enriched", "in cerebrospinal fluid.", "cerebrospinal fluid. it", "fluid. it is", "protease degrades igfbp6.", "the family of insulin", "family of insulin like", "igfbps share 50%", "share 50% amino acid", "50% amino acid identity", "amino acid identity with", "acid identity with conserved", "identity with conserved n", "with conserved n terminal", "conserved n terminal and", "n terminal and c", "terminal and c terminal", "and c terminal regions", "c terminal regions responsible", "terminal regions responsible for", "regions responsible for binding", "responsible for binding insulin", "for binding insulin like", "binding insulin like growth", "insulin like growth factors", "like growth factors i", "growth factors i and", "factors i and ii", "and ii igf", "ii igf i", "igf i and igf", "i and igf ii", "and igf ii .", "igf ii . most", "ii . most circulating", ". most circulating igfs", "most circulating igfs are", "circulating igfs are in", "igfs are in complexes", "are in complexes with", "in complexes with igfbps", "with igfbps which", "igfbps which are", "which are believed to", "are believed to increase", "believed to increase the", "to increase the residence", "increase the residence of", "the residence of igfs", "residence of igfs in", "of igfs in the", "igfs in the body", "the body modulate", "body modulate availability", "modulate availability of igfs", "availability of igfs to", "of igfs to target", "igfs to target receptors", "to target receptors for", "target receptors for igfs", "for igfs reduce", "igfs reduce insulin", "reduce insulin like effects", "insulin like effects of", "like effects of igfs", "of igfs and", "igfs and act", "and act as signaling", "act as signaling molecules", "as signaling molecules independently", "signaling molecules independently of", "molecules independently of igfs.", "independently of igfs. about", "of igfs. about 75%", "igfs. about 75% of", "about 75% of circulating", "75% of circulating igfs", "of circulating igfs are", "igfs are in 1500", "are in 1500 220", "in 1500 220 kda", "1500 220 kda complexes", "220 kda complexes with", "kda complexes with igfbp3", "complexes with igfbp3 and", "with igfbp3 and als.", "igfbp3 and als. such", "and als. such complexes", "als. such complexes are", "such complexes are too", "complexes are too large", "are too large to", "too large to pass", "large to pass the", "to pass the endothelial", "pass the endothelial barrier.", "the endothelial barrier. the", "endothelial barrier. the remaining", "barrier. the remaining 20", "the remaining 20 25%", "remaining 20 25% of", "20 25% of igfs", "25% of igfs are", "of igfs are bound", "igfs are bound to", "are bound to other", "bound to other igfbps", "to other igfbps in", "other igfbps in 40", "igfbps in 40 50", "in 40 50 kda", "40 50 kda complexes.", "50 kda complexes. igfs", "kda complexes. igfs are", "complexes. igfs are released", "igfs are released from", "are released from igf:igfbp", "released from igf:igfbp complexes", "from igf:igfbp complexes by", "igf:igfbp complexes by proteolysis", "complexes by proteolysis of", "by proteolysis of the", "proteolysis of the igfbp.", "of the igfbp. igfs", "the igfbp. igfs become", "igfbp. igfs become active", "igfs become active after", "become active after release", "after release however", "release however igfs", "however igfs may also", "igfs may also have", "may also have activity", "also have activity when", "have activity when still", "activity when still bound", "when still bound to", "still bound to some", "bound to some igfbps.", "to some igfbps. igfbp1", "some igfbps. igfbp1 is", "igfbps. igfbp1 is enriched", "igfbp1 is enriched in", "is enriched in amniotic", "enriched in amniotic fluid", "in amniotic fluid and", "amniotic fluid and is", "fluid and is produced", "and is produced in", "is produced in the", "produced in the liver", "in the liver under", "the liver under control", "liver under control of", "under control of insulin", "of insulin insulin", "insulin insulin suppresses", "insulin suppresses production .", "suppresses production . igfbp1", "production . igfbp1 binding", ". igfbp1 binding stimulates", "igfbp1 binding stimulates igf", "binding stimulates igf function.", "stimulates igf function. it", "igf function. it is", "function. it is unknown", "it is unknown which", "is unknown which if", "unknown which if any", "which if any protease", "if any protease degrades", "any protease degrades igfbp1.", "protease degrades igfbp1. igfbp2", "degrades igfbp1. igfbp2 is", "igfbp1. igfbp2 is enriched", "igfbp2 is enriched in", "is enriched in cerebrospinal", "enriched in cerebrospinal fluid", "cerebrospinal fluid its", "fluid its binding", "its binding inhibits igf", "binding inhibits igf function.", "inhibits igf function. igfbp2", "igf function. igfbp2 is", "function. igfbp2 is not", "igfbp2 is not significantly", "is not significantly degraded", "not significantly degraded in", "significantly degraded in circulation.", "degraded in circulation. igfb3", "circulation. igfb3 which", "igfb3 which binds", "which binds most igf", "binds most igf in", "most igf in the", "igf in the body", "in the body is", "the body is enriched", "body is enriched in", "is enriched in follicular", "enriched in follicular fluid", "in follicular fluid and", "follicular fluid and found", "fluid and found in", "and found in many", "found in many other", "in many other tissues.", "many other tissues. igfbp", "other tissues. igfbp 3", "tissues. igfbp 3 may", "igfbp 3 may be", "3 may be cleaved", "may be cleaved by", "be cleaved by plasmin", "by plasmin thrombin", "thrombin prostate specific", "specific antigen psa", "klk3 matrix", "metalloprotease 1 mmp1", "mmp1 and", "and matrix metalloprotease 2", "metalloprotease 2 mmp2", "2 mmp2 .", "mmp2 . igfbp3 also", ". igfbp3 also binds", "igfbp3 also binds extracellular", "also binds extracellular matrix", "binds extracellular matrix and", "extracellular matrix and binding", "matrix and binding lowers", "and binding lowers its", "binding lowers its affinity", "lowers its affinity for", "its affinity for igfs.", "affinity for igfs. igfbp3", "for igfs. igfbp3 binding", "igfs. igfbp3 binding stimulates", "igfbp3 binding stimulates the", "binding stimulates the effects", "stimulates the effects of", "the effects of igfs.", "effects of igfs. igfbp4", "of igfs. igfbp4 acts", "igfs. igfbp4 acts to", "igfbp4 acts to inhibit", "acts to inhibit igf", "to inhibit igf function", "inhibit igf function and", "igf function and is", "function and is cleaved", "and is cleaved by", "is cleaved by pregnancy", "cleaved by pregnancy associated", "by pregnancy associated plasma", "pregnancy associated plasma protein", "associated plasma protein a", "protein a pappa", "pappa to release", "to release igf. igfbp5", "release igf. igfbp5 is", "igf. igfbp5 is enriched", "igfbp5 is enriched in", "is enriched in bone", "enriched in bone matrix", "bone matrix its", "matrix its binding", "its binding stimulates igf", "stimulates igf function. igfbp5", "igf function. igfbp5 is", "function. igfbp5 is cleaved", "igfbp5 is cleaved by", "associated plasma protein a2", "protein a2 pappa2", "pappa2 adam9", "adam9 complement c1s", "complement c1s from smooth", "c1s from smooth muscle", "smooth muscle and", "muscle and thrombin.", "and thrombin. only the", "thrombin. only the cleavage", "only the cleavage site", "the cleavage site for", "cleavage site for pappa2", "site for pappa2 is", "for pappa2 is known.", "pappa2 is known. igfbp6", "is known. igfbp6 is", "known. igfbp6 is enriched", "igfbp6 is enriched in", "enriched in cerebrospinal fluid.", "in cerebrospinal fluid. it", "cerebrospinal fluid. it is", "fluid. it is unknown", "any protease degrades igfbp6.", "the family of insulin like", "family of insulin like growth", "proteins igfbps share", "igfbps share 50% amino", "share 50% amino acid identity", "50% amino acid identity with", "amino acid identity with conserved", "acid identity with conserved n", "identity with conserved n terminal", "with conserved n terminal and", "conserved n terminal and c", "n terminal and c terminal", "terminal and c terminal regions", "and c terminal regions responsible", "c terminal regions responsible for", "terminal regions responsible for binding", "regions responsible for binding insulin", "responsible for binding insulin like", "for binding insulin like growth", "binding insulin like growth factors", "insulin like growth factors i", "like growth factors i and", "growth factors i and ii", "i and ii igf", "and ii igf i", "ii igf i and", "igf i and igf ii", "i and igf ii .", "and igf ii . most", "igf ii . most circulating", "ii . most circulating igfs", ". most circulating igfs are", "most circulating igfs are in", "circulating igfs are in complexes", "igfs are in complexes with", "are in complexes with igfbps", "complexes with igfbps which", "with igfbps which are", "igfbps which are believed", "which are believed to increase", "are believed to increase the", "believed to increase the residence", "to increase the residence of", "increase the residence of igfs", "the residence of igfs in", "residence of igfs in the", "of igfs in the body", "in the body modulate", "the body modulate availability", "body modulate availability of", "modulate availability of igfs to", "availability of igfs to target", "of igfs to target receptors", "igfs to target receptors for", "to target receptors for igfs", "receptors for igfs reduce", "for igfs reduce insulin", "igfs reduce insulin like", "reduce insulin like effects of", "insulin like effects of igfs", "effects of igfs and", "of igfs and act", "igfs and act as", "and act as signaling molecules", "act as signaling molecules independently", "as signaling molecules independently of", "signaling molecules independently of igfs.", "molecules independently of igfs. about", "independently of igfs. about 75%", "of igfs. about 75% of", "igfs. about 75% of circulating", "about 75% of circulating igfs", "75% of circulating igfs are", "of circulating igfs are in", "circulating igfs are in 1500", "igfs are in 1500 220", "are in 1500 220 kda", "in 1500 220 kda complexes", "1500 220 kda complexes with", "220 kda complexes with igfbp3", "kda complexes with igfbp3 and", "complexes with igfbp3 and als.", "with igfbp3 and als. such", "igfbp3 and als. such complexes", "and als. such complexes are", "als. such complexes are too", "such complexes are too large", "complexes are too large to", "are too large to pass", "too large to pass the", "large to pass the endothelial", "to pass the endothelial barrier.", "pass the endothelial barrier. the", "the endothelial barrier. the remaining", "endothelial barrier. the remaining 20", "barrier. the remaining 20 25%", "the remaining 20 25% of", "remaining 20 25% of igfs", "20 25% of igfs are", "25% of igfs are bound", "of igfs are bound to", "igfs are bound to other", "are bound to other igfbps", "bound to other igfbps in", "to other igfbps in 40", "other igfbps in 40 50", "igfbps in 40 50 kda", "in 40 50 kda complexes.", "40 50 kda complexes. igfs", "50 kda complexes. igfs are", "kda complexes. igfs are released", "complexes. igfs are released from", "igfs are released from igf:igfbp", "are released from igf:igfbp complexes", "released from igf:igfbp complexes by", "from igf:igfbp complexes by proteolysis", "igf:igfbp complexes by proteolysis of", "complexes by proteolysis of the", "by proteolysis of the igfbp.", "proteolysis of the igfbp. igfs", "of the igfbp. igfs become", "the igfbp. igfs become active", "igfbp. igfs become active after", "igfs become active after release", "active after release however", "after release however igfs", "release however igfs may", "however igfs may also have", "igfs may also have activity", "may also have activity when", "also have activity when still", "have activity when still bound", "activity when still bound to", "when still bound to some", "still bound to some igfbps.", "bound to some igfbps. igfbp1", "to some igfbps. igfbp1 is", "some igfbps. igfbp1 is enriched", "igfbps. igfbp1 is enriched in", "igfbp1 is enriched in amniotic", "is enriched in amniotic fluid", "enriched in amniotic fluid and", "in amniotic fluid and is", "amniotic fluid and is produced", "fluid and is produced in", "and is produced in the", "is produced in the liver", "produced in the liver under", "in the liver under control", "the liver under control of", "liver under control of insulin", "control of insulin insulin", "of insulin insulin suppresses", "insulin insulin suppresses production", "insulin suppresses production . igfbp1", "suppresses production . igfbp1 binding", "production . igfbp1 binding stimulates", ". igfbp1 binding stimulates igf", "igfbp1 binding stimulates igf function.", "binding stimulates igf function. it", "stimulates igf function. it is", "igf function. it is unknown", "function. it is unknown which", "it is unknown which if", "is unknown which if any", "unknown which if any protease", "which if any protease degrades", "if any protease degrades igfbp1.", "any protease degrades igfbp1. igfbp2", "protease degrades igfbp1. igfbp2 is", "degrades igfbp1. igfbp2 is enriched", "igfbp1. igfbp2 is enriched in", "igfbp2 is enriched in cerebrospinal", "is enriched in cerebrospinal fluid", "in cerebrospinal fluid its", "cerebrospinal fluid its binding", "fluid its binding inhibits", "its binding inhibits igf function.", "binding inhibits igf function. igfbp2", "inhibits igf function. igfbp2 is", "igf function. igfbp2 is not", "function. igfbp2 is not significantly", "igfbp2 is not significantly degraded", "is not significantly degraded in", "not significantly degraded in circulation.", "significantly degraded in circulation. igfb3", "in circulation. igfb3 which", "circulation. igfb3 which binds", "igfb3 which binds most", "which binds most igf in", "binds most igf in the", "most igf in the body", "igf in the body is", "in the body is enriched", "the body is enriched in", "body is enriched in follicular", "is enriched in follicular fluid", "enriched in follicular fluid and", "in follicular fluid and found", "follicular fluid and found in", "fluid and found in many", "and found in many other", "found in many other tissues.", "in many other tissues. igfbp", "many other tissues. igfbp 3", "other tissues. igfbp 3 may", "tissues. igfbp 3 may be", "igfbp 3 may be cleaved", "3 may be cleaved by", "may be cleaved by plasmin", "cleaved by plasmin thrombin", "plasmin thrombin prostate", "thrombin prostate specific antigen", "prostate specific antigen psa", "antigen psa klk3", "klk3 matrix metalloprotease", "matrix metalloprotease 1 mmp1", "mmp1 and matrix", "matrix metalloprotease 2 mmp2", "metalloprotease 2 mmp2 .", "2 mmp2 . igfbp3", "mmp2 . igfbp3 also binds", ". igfbp3 also binds extracellular", "igfbp3 also binds extracellular matrix", "also binds extracellular matrix and", "binds extracellular matrix and binding", "extracellular matrix and binding lowers", "matrix and binding lowers its", "and binding lowers its affinity", "binding lowers its affinity for", "lowers its affinity for igfs.", "its affinity for igfs. igfbp3", "affinity for igfs. igfbp3 binding", "for igfs. igfbp3 binding stimulates", "igfs. igfbp3 binding stimulates the", "igfbp3 binding stimulates the effects", "binding stimulates the effects of", "stimulates the effects of igfs.", "the effects of igfs. igfbp4", "effects of igfs. igfbp4 acts", "of igfs. igfbp4 acts to", "igfs. igfbp4 acts to inhibit", "igfbp4 acts to inhibit igf", "acts to inhibit igf function", "to inhibit igf function and", "inhibit igf function and is", "igf function and is cleaved", "function and is cleaved by", "and is cleaved by pregnancy", "is cleaved by pregnancy associated", "cleaved by pregnancy associated plasma", "by pregnancy associated plasma protein", "pregnancy associated plasma protein a", "plasma protein a pappa", "a pappa to", "pappa to release igf.", "to release igf. igfbp5 is", "release igf. igfbp5 is enriched", "igf. igfbp5 is enriched in", "igfbp5 is enriched in bone", "is enriched in bone matrix", "in bone matrix its", "bone matrix its binding", "matrix its binding stimulates", "its binding stimulates igf function.", "binding stimulates igf function. igfbp5", "stimulates igf function. igfbp5 is", "igf function. igfbp5 is cleaved", "function. igfbp5 is cleaved by", "igfbp5 is cleaved by pregnancy", "pregnancy associated plasma protein a2", "plasma protein a2 pappa2", "adam9 complement c1s from", "complement c1s from smooth muscle", "from smooth muscle and", "smooth muscle and thrombin.", "muscle and thrombin. only", "and thrombin. only the cleavage", "thrombin. only the cleavage site", "only the cleavage site for", "the cleavage site for pappa2", "cleavage site for pappa2 is", "site for pappa2 is known.", "for pappa2 is known. igfbp6", "pappa2 is known. igfbp6 is", "is known. igfbp6 is enriched", "known. igfbp6 is enriched in", "igfbp6 is enriched in cerebrospinal", "is enriched in cerebrospinal fluid.", "enriched in cerebrospinal fluid. it", "in cerebrospinal fluid. it is", "cerebrospinal fluid. it is unknown", "fluid. it is unknown which", "if any protease degrades igfbp6." ] }, { "record_id": "GLY_000594_1_303", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "381676", "r hsa", "hsa 381676", "r hsa 381676" ] }, { "record_id": "GLY_000594_1_303", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glucagon like", "like peptide", "peptide 1", "regulates insulin", "insulin secretion", "glucagon like peptide", "like peptide 1", "1 glp1", "glp1 regulates", "regulates insulin secretion", "glucagon like peptide 1", "peptide 1 glp1", "glp1 regulates insulin", "like peptide 1 glp1", "1 glp1 regulates", "glp1 regulates insulin secretion", "glp 1", "is secreted", "secreted by", "by l", "l cells", "cells in", "in the", "the intestine", "intestine in", "in response", "response to", "to glucose", "glucose and", "and fatty", "fatty acids.", "acids. glp", "1 circulates", "circulates to", "to the", "the beta", "beta cells", "cells of", "of the", "the pancreas", "pancreas where", "where it", "it binds", "binds a", "a g", "g protein", "protein coupled", "coupled receptor", "glp 1r", "on the", "the plasma", "plasma membrane.", "membrane. the", "the binding", "binding activates", "activates the", "the heterotrimeric", "heterotrimeric g", "protein g", "g s", "causing the", "the alpha", "alpha subunit", "subunit of", "of g", "to exchange", "exchange gdp", "gdp for", "for gtp", "gtp and", "and dissociate", "dissociate from", "from the", "beta and", "and gamma", "gamma subunits.
the", "subunits.
the activated", "activated g", "subunit interacts", "interacts with", "with adenylyl", "adenylyl cyclase", "cyclase viii", "adenylate cyclase", "ac viii", "and activates", "activates ac", "viii to", "to produce", "produce cyclic", "cyclic amp", "camp .", ". camp", "camp then", "then has", "has two", "two effects:", "effects: 1", "camp activates", "activates protein", "protein kinase", "kinase a", "and 2", "activates epac1", "epac1 and", "and epac2", "two guanyl", "guanyl nucleotide", "nucleotide exchange", "exchange factors.
binding", "factors.
binding of", "of camp", "camp to", "to pka", "pka causes", "causes the", "the catalytic", "catalytic subunits", "subunits of", "of pka", "pka to", "to dissociate", "the regulatory", "regulatory subunits", "subunits and", "and become", "become an", "an active", "active kinase.", "kinase. pka", "pka is", "is known", "known to", "to enhance", "enhance insulin", "secretion by", "by closing", "closing atp", "atp sensitive", "sensitive potassium", "potassium channels", "closing voltage", "voltage gated", "gated potassium", "releasing calcium", "calcium from", "the endoplasmic", "endoplasmic reticulum", "and affecting", "affecting insulin", "insulin secretory", "secretory granules.", "granules. the", "the exact", "exact mechanisms", "mechanisms for", "for pka's", "pka's action", "action are", "are not", "not fully", "fully known.", "known. after", "after prolonged", "prolonged increases", "increases in", "in camp", "translocates to", "the nucleus", "nucleus where", "it regulates", "regulates the", "the pdx", "pdx 1", "1 and", "and creb", "creb transcription", "transcription factors", "activating transcription", "transcription of", "the insulin", "insulin gene.
camp", "gene.
camp produced", "produced by", "by ac", "viii also", "also activates", "which catalyze", "catalyze the", "the exchange", "exchange of", "of gtp", "gtp for", "for gdp", "gdp on", "on g", "g proteins", "notably rap1a.", "rap1a. rap1a", "rap1a regulates", "secretory granules", "granules and", "and is", "is believed", "believed to", "to activate", "activate the", "the raf/mek/erk", "raf/mek/erk mitogenic", "mitogenic pathway", "pathway leading", "leading to", "to proliferation", "proliferation of", "of beta", "beta cells.", "cells. the", "the epac", "epac proteins", "proteins also", "also interact", "interact with", "with ryr", "ryr calcium", "calcium channels", "channels on", "the sur1", "sur1 subunits", "of atp", "and the", "the piccolo:rim2", "piccolo:rim2 calcium", "calcium sensor", "sensor at", "at the", "1 glp", "1 is", "is secreted by", "secreted by l", "by l cells", "l cells in", "cells in the", "in the intestine", "the intestine in", "intestine in response", "in response to", "response to glucose", "to glucose and", "glucose and fatty", "and fatty acids.", "fatty acids. glp", "acids. glp 1", "glp 1 circulates", "1 circulates to", "circulates to the", "to the beta", "the beta cells", "beta cells of", "cells of the", "of the pancreas", "the pancreas where", "pancreas where it", "where it binds", "it binds a", "binds a g", "a g protein", "g protein coupled", "protein coupled receptor", "receptor glp", "1r on", "on the plasma", "the plasma membrane.", "plasma membrane. the", "membrane. the binding", "the binding activates", "binding activates the", "activates the heterotrimeric", "the heterotrimeric g", "heterotrimeric g protein", "g protein g", "protein g s", "causing the alpha", "the alpha subunit", "alpha subunit of", "subunit of g", "of g s", "s to", "to exchange gdp", "exchange gdp for", "gdp for gtp", "for gtp and", "gtp and dissociate", "and dissociate from", "dissociate from the", "from the beta", "the beta and", "beta and gamma", "and gamma subunits.
the", "gamma subunits.
the activated", "subunits.
the activated g", "activated g s", "s alpha", "alpha subunit interacts", "subunit interacts with", "interacts with adenylyl", "with adenylyl cyclase", "adenylyl cyclase viii", "viii adenylate", "adenylate cyclase viii", "viii ac", "viii and", "and activates ac", "activates ac viii", "ac viii to", "viii to produce", "to produce cyclic", "produce cyclic amp", "amp camp", "camp . camp", ". camp then", "camp then has", "then has two", "has two effects:", "two effects: 1", "1 camp", "camp activates protein", "activates protein kinase", "protein kinase a", "a pka", "2 camp", "camp activates epac1", "activates epac1 and", "epac1 and epac2", "epac2 two", "two guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange factors.
binding", "exchange factors.
binding of", "factors.
binding of camp", "of camp to", "camp to pka", "to pka causes", "pka causes the", "causes the catalytic", "the catalytic subunits", "catalytic subunits of", "subunits of pka", "of pka to", "pka to dissociate", "to dissociate from", "from the regulatory", "the regulatory subunits", "regulatory subunits and", "subunits and become", "and become an", "become an active", "an active kinase.", "active kinase. pka", "kinase. pka is", "pka is known", "is known to", "known to enhance", "to enhance insulin", "enhance insulin secretion", "insulin secretion by", "secretion by closing", "by closing atp", "closing atp sensitive", "atp sensitive potassium", "sensitive potassium channels", "channels closing", "closing voltage gated", "voltage gated potassium", "gated potassium channels", "channels releasing", "releasing calcium from", "calcium from the", "from the endoplasmic", "the endoplasmic reticulum", "reticulum and", "and affecting insulin", "affecting insulin secretory", "insulin secretory granules.", "secretory granules. the", "granules. the exact", "the exact mechanisms", "exact mechanisms for", "mechanisms for pka's", "for pka's action", "pka's action are", "action are not", "are not fully", "not fully known.", "fully known. after", "known. after prolonged", "after prolonged increases", "prolonged increases in", "increases in camp", "camp pka", "pka translocates", "translocates to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it regulates", "it regulates the", "regulates the pdx", "the pdx 1", "pdx 1 and", "1 and creb", "and creb transcription", "creb transcription factors", "factors activating", "activating transcription of", "transcription of the", "of the insulin", "the insulin gene.
camp", "insulin gene.
camp produced", "gene.
camp produced by", "produced by ac", "by ac viii", "ac viii also", "viii also activates", "also activates epac1", "epac2 which", "which catalyze the", "catalyze the exchange", "the exchange of", "exchange of gtp", "of gtp for", "gtp for gdp", "for gdp on", "gdp on g", "on g proteins", "proteins notably", "notably rap1a. rap1a", "rap1a. rap1a regulates", "rap1a regulates insulin", "regulates insulin secretory", "insulin secretory granules", "secretory granules and", "granules and is", "and is believed", "is believed to", "believed to activate", "to activate the", "activate the raf/mek/erk", "the raf/mek/erk mitogenic", "raf/mek/erk mitogenic pathway", "mitogenic pathway leading", "pathway leading to", "leading to proliferation", "to proliferation of", "proliferation of beta", "of beta cells.", "beta cells. the", "cells. the epac", "the epac proteins", "epac proteins also", "proteins also interact", "also interact with", "interact with ryr", "with ryr calcium", "ryr calcium channels", "calcium channels on", "channels on the", "on the endoplasmic", "reticulum the", "the sur1 subunits", "sur1 subunits of", "subunits of atp", "of atp sensitive", "channels and", "and the piccolo:rim2", "the piccolo:rim2 calcium", "piccolo:rim2 calcium sensor", "calcium sensor at", "sensor at the", "at the plasma", "peptide 1 glp", "1 glp 1", "glp 1 is", "1 is secreted", "is secreted by l", "secreted by l cells", "by l cells in", "l cells in the", "cells in the intestine", "in the intestine in", "the intestine in response", "intestine in response to", "in response to glucose", "response to glucose and", "to glucose and fatty", "glucose and fatty acids.", "and fatty acids. glp", "fatty acids. glp 1", "acids. glp 1 circulates", "glp 1 circulates to", "1 circulates to the", "circulates to the beta", "to the beta cells", "the beta cells of", "beta cells of the", "cells of the pancreas", "of the pancreas where", "the pancreas where it", "pancreas where it binds", "where it binds a", "it binds a g", "binds a g protein", "a g protein coupled", "g protein coupled receptor", "coupled receptor glp", "receptor glp 1r", "glp 1r on", "1r on the", "on the plasma membrane.", "the plasma membrane. the", "plasma membrane. the binding", "membrane. the binding activates", "the binding activates the", "binding activates the heterotrimeric", "activates the heterotrimeric g", "the heterotrimeric g protein", "heterotrimeric g protein g", "g protein g s", "s causing", "causing the alpha subunit", "the alpha subunit of", "alpha subunit of g", "subunit of g s", "g s to", "s to exchange", "to exchange gdp for", "exchange gdp for gtp", "gdp for gtp and", "for gtp and dissociate", "gtp and dissociate from", "and dissociate from the", "dissociate from the beta", "from the beta and", "the beta and gamma", "beta and gamma subunits.
the", "and gamma subunits.
the activated", "gamma subunits.
the activated g", "subunits.
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camp", "the insulin gene.
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camp produced by ac", "produced by ac viii", "by ac viii also", "ac viii also activates", "viii also activates epac1", "also activates epac1 and", "and epac2 which", "epac2 which catalyze", "which catalyze the exchange", "catalyze the exchange of", "the exchange of gtp", "exchange of gtp for", "of gtp for gdp", "gtp for gdp on", "for gdp on g", "gdp on g proteins", "g proteins notably", "proteins notably rap1a.", "notably rap1a. rap1a regulates", "rap1a. rap1a regulates insulin", "rap1a regulates insulin secretory", "regulates insulin secretory granules", "insulin secretory granules and", "secretory granules and is", "granules and is believed", "and is believed to", "is believed to activate", "believed to activate the", "to activate the raf/mek/erk", "activate the raf/mek/erk mitogenic", "the raf/mek/erk mitogenic pathway", "raf/mek/erk mitogenic pathway leading", "mitogenic pathway leading to", "pathway leading to proliferation", "leading to proliferation of", "to proliferation of beta", "proliferation of beta cells.", "of beta cells. the", "beta cells. the epac", "cells. the epac proteins", "the epac proteins also", "epac proteins also interact", "proteins also interact with", "also interact with ryr", "interact with ryr calcium", "with ryr calcium channels", "ryr calcium channels on", "calcium channels on the", "channels on the endoplasmic", "on the endoplasmic reticulum", "endoplasmic reticulum the", "reticulum the sur1", "the sur1 subunits of", "sur1 subunits of atp", "subunits of atp sensitive", "of atp sensitive potassium", "potassium channels and", "channels and the", "and the piccolo:rim2 calcium", "the piccolo:rim2 calcium sensor", "piccolo:rim2 calcium sensor at", "calcium sensor at the", "sensor at the plasma", "at the plasma membrane.", "like peptide 1 glp", "peptide 1 glp 1", "glp 1 is secreted", "1 is secreted by", "is secreted by l cells", "secreted by l cells in", "by l cells in the", "l cells in the intestine", "cells in the intestine in", "in the intestine in response", "the intestine in response to", "intestine in response to glucose", "in response to glucose and", "response to glucose and fatty", "to glucose and fatty acids.", "glucose and fatty acids. glp", "and fatty acids. glp 1", "fatty acids. glp 1 circulates", "acids. glp 1 circulates to", "glp 1 circulates to the", "1 circulates to the beta", "circulates to the beta cells", "to the beta cells of", "the beta cells of the", "beta cells of the pancreas", "cells of the pancreas where", "of the pancreas where it", "the pancreas where it binds", "pancreas where it binds a", "where it binds a g", "it binds a g protein", "binds a g protein coupled", "a g protein coupled receptor", "protein coupled receptor glp", "coupled receptor glp 1r", "glp 1r on the", "1r on the plasma", "on the plasma membrane. the", "the plasma membrane. the binding", "plasma membrane. the binding activates", "membrane. the binding activates the", "the binding activates the heterotrimeric", "binding activates the heterotrimeric g", "activates the heterotrimeric g protein", "the heterotrimeric g protein g", "heterotrimeric g protein g s", "g s causing", "s causing the", "causing the alpha subunit of", "the alpha subunit of g", "alpha subunit of g s", "of g s to", "g s to exchange", "s to exchange gdp", "to exchange gdp for gtp", "exchange gdp for gtp and", "gdp for gtp and dissociate", "for gtp and dissociate from", "gtp and dissociate from the", "and dissociate from the beta", "dissociate from the beta and", "from the beta and gamma", "the beta and gamma subunits.
the", "beta and gamma subunits.
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the activated g", "gamma subunits.
the activated g s", "activated g s alpha", "g s alpha subunit", "s alpha subunit interacts", "alpha subunit interacts with adenylyl", "subunit interacts with adenylyl cyclase", "interacts with adenylyl cyclase viii", "adenylyl cyclase viii adenylate", "cyclase viii adenylate cyclase", "viii adenylate cyclase viii", "adenylate cyclase viii ac", "cyclase viii ac viii", "ac viii and activates", "viii and activates ac", "and activates ac viii to", "activates ac viii to produce", "ac viii to produce cyclic", "viii to produce cyclic amp", "produce cyclic amp camp", "cyclic amp camp .", "amp camp . camp", "camp . camp then has", ". camp then has two", "camp then has two effects:", "then has two effects: 1", "two effects: 1 camp", "effects: 1 camp activates", "1 camp activates protein", "camp activates protein kinase a", "protein kinase a pka", "pka and 2", "and 2 camp activates", "2 camp activates epac1", "camp activates epac1 and epac2", "epac1 and epac2 two", "and epac2 two guanyl", "epac2 two guanyl nucleotide", "two guanyl nucleotide exchange factors.
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camp", "of the insulin gene.
camp produced", "the insulin gene.
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camp produced by ac", "gene.
camp produced by ac viii", "produced by ac viii also", "by ac viii also activates", "ac viii also activates epac1", "viii also activates epac1 and", "also activates epac1 and epac2", "epac1 and epac2 which", "and epac2 which catalyze", "epac2 which catalyze the", "which catalyze the exchange of", "catalyze the exchange of gtp", "the exchange of gtp for", "exchange of gtp for gdp", "of gtp for gdp on", "gtp for gdp on g", "for gdp on g proteins", "on g proteins notably", "g proteins notably rap1a.", "proteins notably rap1a. rap1a", "notably rap1a. rap1a regulates insulin", "rap1a. rap1a regulates insulin secretory", "rap1a regulates insulin secretory granules", "regulates insulin secretory granules and", "insulin secretory granules and is", "secretory granules and is believed", "granules and is believed to", "and is believed to activate", "is believed to activate the", "believed to activate the raf/mek/erk", "to activate the raf/mek/erk mitogenic", "activate the raf/mek/erk mitogenic pathway", "the raf/mek/erk mitogenic pathway leading", "raf/mek/erk mitogenic pathway leading to", "mitogenic pathway leading to proliferation", "pathway leading to proliferation of", "leading to proliferation of beta", "to proliferation of beta cells.", "proliferation of beta cells. the", "of beta cells. the epac", "beta cells. the epac proteins", "cells. the epac proteins also", "the epac proteins also interact", "epac proteins also interact with", "proteins also interact with ryr", "also interact with ryr calcium", "interact with ryr calcium channels", "with ryr calcium channels on", "ryr calcium channels on the", "calcium channels on the endoplasmic", "channels on the endoplasmic reticulum", "the endoplasmic reticulum the", "endoplasmic reticulum the sur1", "reticulum the sur1 subunits", "the sur1 subunits of atp", "sur1 subunits of atp sensitive", "subunits of atp sensitive potassium", "of atp sensitive potassium channels", "sensitive potassium channels and", "potassium channels and the", "channels and the piccolo:rim2", "and the piccolo:rim2 calcium sensor", "the piccolo:rim2 calcium sensor at", "piccolo:rim2 calcium sensor at the", "calcium sensor at the plasma", "sensor at the plasma membrane." ] }, { "record_id": "GLY_000594_1_304", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "381753", "r hsa", "hsa 381753", "r hsa 381753" ] }, { "record_id": "GLY_000594_1_304", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "olfactory signaling", "signaling pathway", "olfactory signaling pathway", "mammalian olfactory", "olfactory receptor", "also called", "called odorant", "odorant receptor", "genes were", "were discovered", "discovered in", "in rats", "rats by", "by linda", "linda buck", "buck and", "and richard", "richard axel", "who predicted", "predicted that", "that odorants", "odorants would", "would be", "be detected", "detected by", "by a", "a large", "large family", "family of", "of g", "g protein", "protein coupled", "coupled receptors", "that are", "are selectively", "selectively expressed", "expressed in", "in the", "the olfactory", "olfactory epithelium.", "epithelium. this", "this prediction", "prediction was", "was based", "based on", "on previous", "previous biochemical", "biochemical evidence", "evidence that", "that camp", "camp levels", "levels increased", "increased in", "in olfactory", "olfactory neurons", "neurons upon", "upon odor", "odor stimulation.", "stimulation. these", "these predictions", "predictions proved", "proved to", "to be", "be accurate", "and buck", "and axel", "axel received", "received a", "a nobel", "nobel prize", "prize for", "for this", "this and", "and subsequent", "subsequent work", "reviewed in", "in keller", "keller &", "& vosshall", "vosshall 2008", "2008 .
subsequent", ".
subsequent work", "work in", "in mice", "mice and", "and other", "other vertebrates", "vertebrates has", "has confirmed", "confirmed that", "that or", "or genes", "genes are", "are comprised", "comprised of", "of a", "a very", "very large", "epithelium. although", "although some", "some or", "or are", "are also", "also expressed", "expressed selectively", "selectively in", "in one", "one or", "or a", "a few", "few other", "other tissues", "their expression", "expression in", "olfactory epithelium", "epithelium generally", "generally indicates", "indicates a", "a functional", "functional role", "role in", "in mediating", "mediating olfaction", "where they", "they couple", "couple binding", "binding by", "by odorant", "odorant ligands", "ligands with", "with intracellular", "intracellular olfactory", "olfactory signaling.", "note: the", "the other", "other subclasses", "subclasses of", "of gpcr", "gpcr signaling", "signaling pathways", "pathways are", "are described", "described under", "under \\gpcr", "\\gpcr signaling\\.", "signaling\\.
the", "
the ligands", "ligands for", "for ors", "ors are", "are diverse", "ranging from", "from chemical", "chemical compounds", "compounds to", "to peptides.", "peptides. intracellular", "intracellular signaling", "signaling by", "by or", "or proteins", "proteins in", "other mammalian", "mammalian systems", "systems is", "is known", "known to", "be mediated", "mediated via", "via direct", "direct interactions", "interactions of", "of or", "proteins with", "with an", "an olfactory", "olfactory specific", "specific heterotrimeric", "heterotrimeric g", "that contains", "contains an", "specific g", "g alpha", "alpha protein:", "protein: g", "alpha s", "s olph", "also named", "named \\gnal\\", "\\gnal\\ .
in", ".
in model", "model genetic", "genetic systems", "systems such", "such as", "as mice", "many candidate", "candidate or", "genes have", "have been", "been shown", "shown experimentally", "experimentally to", "to function", "function in", "2008 .", ". for", "for the", "the human", "human or", "experimental analysis", "analysis has", "has been", "been more", "more limited", "some specific", "specific or", "as or7d4", "or7d4 and", "and or11h7p", "or11h7p have", "been confirmed", "confirmed to", "to mediate", "mediate olfactory", "olfactory response", "response and", "and signaling", "signaling in", "in humans", "humans for", "for specific", "specific chemical", "chemical odorants", "keller et", "et al.", "al. 2007", "abbafy 2007", "2007 .", ". mice", "other rodents", "rodents are", "are believed", "believed to", "to have", "have about", "about 1000", "1000 functional", "functional or", "as well", "well as", "as many", "many additional", "additional pseudogenes.", "on sequence", "sequence similarities", "there are", "are 960", "960 human", "but approximately", "approximately half", "half of", "of these", "these are", "are pseudogenes", "keller 2008", ". in", "essentially all", "all olfactory", "signaling requires", "requires g", "mouse g", "g olf", "olf knockouts", "knockouts have", "shown to", "to lack", "lack olfactory", "olfactory responses", "belluscio 1998", "1998 .", ". bona", "bona fide", "fide human", "genes identified", "identified by", "by sequence", "sequence similarity", "not pseudogenes", "pseudogenes with", "with function", "function blocking", "blocking mutations", "are expressed", "epithelium are", "are expected", "expected to", "to interact", "interact with", "with g", "s olf", "olf containing", "containing g", "protein trimers.", "trimers.
of", "
of the", "the 960", "genes and", "and pseudogenes", "there is", "is experimental", "experimental evidence", "that indicates", "indicates over", "over 430", "430 are", "in human", "human olfactory", "including 80", "80 expressed", "expressed or", "or pseudogenes", "zhang 2007", "2007 .
when", ".
when expressed", "in model", "model cell", "cell systems", "systems mammalian", "olfactory receptors", "are typically", "typically retained", "retained in", "the er", "er and", "and degraded", "degraded by", "by the", "the proteasome", "mcclintock et", "al. 1997", "1997 .", ". a", "a study", "study using", "using caenorhabditis", "caenorhabditis elegans", "elegans showed", "showed that", "that the", "the transport", "transport of", "of ors", "ors to", "to the", "the cilia", "cilia of", "of olfactory", "neurons required", "required the", "the expression", "expression and", "and association", "association of", "ors with", "with a", "a transmembrane", "transmembrane protein", "dwyer et", "al. 1998", ". co", "co transfection", "transfection of", "of rat", "rat ors", "with odr4", "odr4 enhanced", "enhanced the", "transport and", "and expression", "expression of", "ors at", "at the", "the cell", "cell surface", "gimelbrant et", "al. 2001", "2001 .", ". these", "these studies", "studies suggested", "suggested that", "that olfactory", "neurons might", "might have", "have a", "a selective", "selective molecular", "molecular machinery", "machinery that", "that promotes", "promotes expression", "the cells", "cells surface.", "surface. two", "two human", "human protein", "protein families", "families have", "been identified", "identified as", "as potential", "potential accessory", "accessory proteins", "proteins involved", "involved in", "the trafficking", "trafficking of", "the plasma", "plasma membrane", "saito et", "al. 2004", "2004 .", ". receptor", "receptor transporting", "transporting proteins", "proteins 1", "1 and", "and 2", "both strongly", "strongly induced", "induced expression", "of several", "several ors", "cell surface.", "surface. to", "to a", "a lesser", "lesser extent", "the receptor", "receptor expression", "expression enhancing", "enhancing protein", "protein 1", "also promoted", "promoted cell", "surface expression.", "expression. these", "these proteins", "proteins are", "are specifically", "specifically expressed", "neurons with", "with no", "no expression", "in testis", "where a", "a subset", "subset of", "parmentier et", "al. 1992", "spehr et", "al. 2003", "2003 .", ". other", "other members", "members of", "of the", "the rtp", "rtp and", "and reep", "reep families", "a widespread", "widespread distribution.", "distribution. rtp3", "rtp3 and", "and rtp4", "rtp4 have", "to promote", "promote cell", "surface expression", "the bitter", "bitter taste", "taste receptors", "behrens et", "al. 2006", "2006 .", ". reep1", "reep1 and", "and reep5", "also known", "known as", "as dp1", "are involved", "in shaping", "shaping the", "er by", "by linking", "linking microtubule", "microtubule fibers", "fibers to", "park et", "al. 2010", "voeltz et", "a recent", "recent study", "study looking", "looking at", "the role", "role of", "of reep", "reep in", "of alpha2a", "and alpha2c", "alpha2c adrenergic", "adrenergic receptors", "receptors showed", "that reep1", "reep1 2", "2 and", "and 6", "6 enhance", "enhance the", "of alpha2c", "but not", "not alpha2a", "by increasing", "increasing the", "the capacity", "capacity of", "of er", "er cargo", "thereby allowing", "allowing more", "more receptors", "receptors to", "to reach", "reach the", "bjork et", "al. 2013", "2013 .", ". unlike", "unlike rtp1", "6 are", "are only", "only present", "present in", "do not", "not traffic", "traffic to", "membrane and", "and specifically", "specifically interact", "with the", "the minimal/non", "minimal/non glycosylated", "glycosylated forms", "forms of", "alpha2c via", "via an", "an interaction", "interaction with", "with its", "its c", "c terminus", ". reeps", "reeps may", "may function", "function as", "as general", "general modulators", "modulators of", "rather than", "than specifically", "specifically interacting", "interacting with", "with gpcrs.", "gpcrs. loss", "loss of", "of association", "of reep2", "reep2 with", "with membranes", "membranes leads", "leads to", "to hereditary", "hereditary spastic", "spastic paraplegia", "esteves et", "al. 2014", "2014 .
olfactory", ".
olfactory receptors", "odorant receptors", "are present", "present on", "on the", "membrane of", "of cilia", "olfactory sensory", "sensory neurons", "neurons located", "located in", "epithelium of", "the nasal", "nasal sinus.", "sinus. each", "each mature", "mature neuron", "neuron expresses", "expresses only", "only one", "or gene", "in nagai", "nagai et", "al. 2016", "and each", "each or", "or binds", "binds one", "one particular", "particular volatile", "volatile chemical", "chemical or", "or set", "set of", "of volatile", "volatile chemicals", "as odorants.", "odorants. the", "the binding", "binding of", "of an", "an odorant", "odorant to", "to an", "an or", "mainland et", "al. 2015", "causes a", "a conformational", "conformational change", "change in", "receptor that", "that activates", "activates the", "the g", "alpha subunit", "an associated", "associated heterotrimeric", "protein complex", "complex to", "to exchange", "exchange gdp", "gdp for", "for gtp", "inferred from", "from mouse", "mouse homologs", "homologs in", "in jones", "jones et", "al. 1990", "1990 .", ". gnal:gtp", "gnal:gtp and", "and the", "the gbeta:ggamma", "gbeta:ggamma subcomplex", "dissociate from", "from the", "receptor and", "and gnal:gtp", "gnal:gtp then", "then binds", "binds and", "and activates", "activates adenylate", "adenylate cyclase", "cyclase 3", "from rat", "rat homologs", "in bakalyar", "bakalyar and", "and reed", "reed 1990", "in boccaccio", "boccaccio et", "al. 2021", "2021 .", ". cyclic", "cyclic amp", "amp produced", "produced by", "by adcy3", "adcy3 binds", "and opens", "opens the", "olfactory cyclic", "cyclic nucleotide", "nucleotide gated", "gated channel", "cng channel", "composed of", "of cnga2", "and cngb", "cngb isoform", "isoform 1b", "in liman", "liman and", "buck 1994", "1994 .", ". the", "the cng", "channel translocates", "translocates sodium", "sodium and", "and calcium", "calcium cations", "cations from", "the extracellular", "extracellular region", "region into", "into the", "the cytosol.", "cytosol. the", "the resulting", "resulting cytosolic", "cytosolic calcium", "calcium ions", "ions bind", "bind ano2", "ano2 and", "and increase", "increase the", "of chloride", "chloride ions", "ions by", "by ano2", "ano2 from", "the cytosol", "cytosol to", "in pifferi", "pifferi et", "al. 2009", "stephan et", "2009 .", "the translocations", "translocations of", "of ions", "ions across", "across the", "membrane causes", "causes depolarization", "depolarization of", "the neuron", "neuron yielding", "yielding a", "a receptor", "receptor potential", "potential and", "and action", "action potential", "potential that", "that is", "is transmitted", "transmitted to", "olfactory bulb", "bulb of", "the brain.", "mammalian olfactory receptor", "receptor or", "or also", "also called odorant", "called odorant receptor", "receptor genes", "genes were discovered", "were discovered in", "discovered in rats", "in rats by", "rats by linda", "by linda buck", "linda buck and", "buck and richard", "and richard axel", "axel who", "who predicted that", "predicted that odorants", "that odorants would", "odorants would be", "would be detected", "be detected by", "detected by a", "by a large", "a large family", "large family of", "family of g", "of g protein", "g protein coupled", "protein coupled receptors", "receptors gpcrs", "gpcrs that", "that are selectively", "are selectively expressed", "selectively expressed in", "expressed in the", "in the olfactory", "the olfactory epithelium.", "olfactory epithelium. this", "epithelium. this prediction", "this prediction was", "prediction was based", "was based on", "based on previous", "on previous biochemical", "previous biochemical evidence", "biochemical evidence that", "evidence that camp", "that camp levels", "camp levels increased", "levels increased in", "increased in olfactory", "in olfactory neurons", "olfactory neurons upon", "neurons upon odor", "upon odor stimulation.", "odor stimulation. these", "stimulation. these predictions", "these predictions proved", "predictions proved to", "proved to be", "to be accurate", "accurate and", "and buck and", "buck and axel", "and axel received", "axel received a", "received a nobel", "a nobel prize", "nobel prize for", "prize for this", "for this and", "this and subsequent", "and subsequent work", "work reviewed", "reviewed in keller", "in keller &", "keller & vosshall", "& vosshall 2008", "vosshall 2008 .
subsequent", "2008 .
subsequent work", ".
subsequent work in", "work in mice", "in mice and", "mice and other", "and other vertebrates", "other vertebrates has", "vertebrates has confirmed", "has confirmed that", "confirmed that or", "that or genes", "or genes are", "genes are comprised", "are comprised of", "comprised of a", "of a very", "a very large", "very large family", "expressed in olfactory", "in olfactory epithelium.", "olfactory epithelium. although", "epithelium. although some", "although some or", "some or are", "or are also", "are also expressed", "also expressed selectively", "expressed selectively in", "selectively in one", "in one or", "one or a", "or a few", "a few other", "few other tissues", "tissues their", "their expression in", "expression in olfactory", "in olfactory epithelium", "olfactory epithelium generally", "epithelium generally indicates", "generally indicates a", "indicates a functional", "a functional role", "functional role in", "role in mediating", "in mediating olfaction", "olfaction where", "where they couple", "they couple binding", "couple binding by", "binding by odorant", "by odorant ligands", "odorant ligands with", "ligands with intracellular", "with intracellular olfactory", "intracellular olfactory signaling.", "signaling. note:", "note: the other", "the other subclasses", "other subclasses of", "subclasses of gpcr", "of gpcr signaling", "gpcr signaling pathways", "signaling pathways are", "pathways are described", "are described under", "described under \\gpcr", "under \\gpcr signaling\\.", "\\gpcr signaling\\.
the", "signaling\\.
the ligands", "
the ligands for", "ligands for ors", "for ors are", "ors are diverse", "diverse ranging", "ranging from chemical", "from chemical compounds", "chemical compounds to", "compounds to peptides.", "to peptides. intracellular", "peptides. intracellular signaling", "intracellular signaling by", "signaling by or", "by or proteins", "or proteins in", "proteins in mice", "and other mammalian", "other mammalian systems", "mammalian systems is", "systems is known", "is known to", "known to be", "to be mediated", "be mediated via", "mediated via direct", "via direct interactions", "direct interactions of", "interactions of or", "of or proteins", "or proteins with", "proteins with an", "with an olfactory", "an olfactory specific", "olfactory specific heterotrimeric", "specific heterotrimeric g", "heterotrimeric g protein", "protein that", "that contains an", "contains an olfactory", "olfactory specific g", "specific g alpha", "g alpha protein:", "alpha protein: g", "protein: g alpha", "g alpha s", "alpha s olph", "olph also", "also named \\gnal\\", "named \\gnal\\ .
in", "\\gnal\\ .
in model", ".
in model genetic", "model genetic systems", "genetic systems such", "systems such as", "such as mice", "mice many", "many candidate or", "candidate or genes", "or genes have", "genes have been", "have been shown", "been shown experimentally", "shown experimentally to", "experimentally to function", "to function in", "function in olfactory", "in olfactory signaling", "signaling reviewed", "vosshall 2008 .", "2008 . for", ". for the", "for the human", "the human or", "human or genes", "genes experimental", "experimental analysis has", "analysis has been", "has been more", "been more limited", "limited although", "although some specific", "some specific or", "specific or genes", "genes such", "such as or7d4", "as or7d4 and", "or7d4 and or11h7p", "and or11h7p have", "or11h7p have been", "have been confirmed", "been confirmed to", "confirmed to mediate", "to mediate olfactory", "mediate olfactory response", "olfactory response and", "response and signaling", "and signaling in", "signaling in humans", "in humans for", "humans for specific", "for specific chemical", "specific chemical odorants", "odorants keller", "keller et al.", "et al. 2007", "2007 abbafy", "abbafy 2007 .", "2007 . mice", ". mice and", "and other rodents", "other rodents are", "rodents are believed", "are believed to", "believed to have", "to have about", "have about 1000", "about 1000 functional", "1000 functional or", "functional or genes", "genes as", "as well as", "well as many", "as many additional", "many additional pseudogenes.", "pseudogenes. based", "based on sequence", "on sequence similarities", "similarities there", "there are 960", "are 960 human", "960 human or", "genes but", "but approximately half", "approximately half of", "half of these", "of these are", "these are pseudogenes", "pseudogenes keller", "keller 2008 .", "2008 . in", ". in mice", "mice essentially", "essentially all olfactory", "all olfactory signaling", "olfactory signaling requires", "signaling requires g", "requires g alpha", "mouse g olf", "g olf knockouts", "olf knockouts have", "knockouts have been", "been shown to", "shown to lack", "to lack olfactory", "lack olfactory responses", "responses belluscio", "belluscio 1998 .", "1998 . bona", ". bona fide", "bona fide human", "fide human or", "or genes identified", "genes identified by", "identified by sequence", "by sequence similarity", "similarity not", "not pseudogenes with", "pseudogenes with function", "with function blocking", "function blocking mutations", "mutations that", "that are expressed", "are expressed in", "olfactory epithelium are", "epithelium are expected", "are expected to", "expected to interact", "to interact with", "interact with g", "with g alpha", "alpha s olf", "s olf containing", "olf containing g", "containing g protein", "g protein trimers.", "protein trimers.
of", "trimers.
of the", "
of the 960", "the 960 human", "or genes and", "genes and pseudogenes", "pseudogenes there", "there is experimental", "is experimental evidence", "experimental evidence that", "evidence that indicates", "that indicates over", "indicates over 430", "over 430 are", "430 are expressed", "expressed in human", "in human olfactory", "human olfactory epithelium", "epithelium including", "including 80 expressed", "80 expressed or", "expressed or pseudogenes", "pseudogenes zhang", "zhang 2007 .
when", "2007 .
when expressed", ".
when expressed in", "expressed in model", "in model cell", "model cell systems", "cell systems mammalian", "systems mammalian olfactory", "mammalian olfactory receptors", "receptors ors", "are typically retained", "typically retained in", "retained in the", "in the er", "the er and", "er and degraded", "and degraded by", "degraded by the", "by the proteasome", "proteasome mcclintock", "mcclintock et al.", "et al. 1997", "al. 1997 .", "1997 . a", ". a study", "a study using", "study using caenorhabditis", "using caenorhabditis elegans", "caenorhabditis elegans showed", "elegans showed that", "showed that the", "that the transport", "the transport of", "transport of ors", "of ors to", "ors to the", "to the cilia", "the cilia of", "cilia of olfactory", "of olfactory neurons", "olfactory neurons required", "neurons required the", "required the expression", "the expression and", "expression and association", "and association of", "association of ors", "of ors with", "ors with a", "with a transmembrane", "a transmembrane protein", "protein odr4", "odr4 dwyer", "dwyer et al.", "et al. 1998", "al. 1998 .", "1998 . co", ". co transfection", "co transfection of", "transfection of rat", "of rat ors", "rat ors with", "ors with odr4", "with odr4 enhanced", "odr4 enhanced the", "enhanced the transport", "the transport and", "transport and expression", "and expression of", "expression of ors", "of ors at", "ors at the", "at the cell", "the cell surface", "surface gimelbrant", "gimelbrant et al.", "et al. 2001", "al. 2001 .", "2001 . these", ". these studies", "these studies suggested", "studies suggested that", "suggested that olfactory", "that olfactory neurons", "olfactory neurons might", "neurons might have", "might have a", "have a selective", "a selective molecular", "selective molecular machinery", "molecular machinery that", "machinery that promotes", "that promotes expression", "promotes expression of", "at the cells", "the cells surface.", "cells surface. two", "surface. two human", "two human protein", "human protein families", "protein families have", "families have been", "have been identified", "been identified as", "identified as potential", "as potential accessory", "potential accessory proteins", "accessory proteins involved", "proteins involved in", "involved in the", "in the trafficking", "the trafficking of", "trafficking of ors", "to the plasma", "the plasma membrane", "membrane saito", "saito et al.", "et al. 2004", "al. 2004 .", "2004 . receptor", ". receptor transporting", "receptor transporting proteins", "transporting proteins 1", "proteins 1 and", "1 and 2", "2 rtp1", "rtp1 rtp2", "rtp2 both", "both strongly induced", "strongly induced expression", "induced expression of", "expression of several", "of several ors", "several ors at", "the cell surface.", "cell surface. to", "surface. to a", "to a lesser", "a lesser extent", "extent the", "the receptor expression", "receptor expression enhancing", "expression enhancing protein", "enhancing protein 1", "1 reep1", "reep1 also", "also promoted cell", "promoted cell surface", "cell surface expression.", "surface expression. these", "expression. these proteins", "these proteins are", "proteins are specifically", "are specifically expressed", "specifically expressed in", "olfactory neurons with", "neurons with no", "with no expression", "no expression in", "expression in testis", "testis where", "where a subset", "a subset of", "subset of ors", "of ors are", "ors are expressed", "expressed parmentier", "parmentier et al.", "et al. 1992", "1992 spehr", "spehr et al.", "et al. 2003", "al. 2003 .", "2003 . other", ". other members", "other members of", "members of the", "of the rtp", "the rtp and", "rtp and reep", "and reep families", "reep families have", "families have a", "have a widespread", "a widespread distribution.", "widespread distribution. rtp3", "distribution. rtp3 and", "rtp3 and rtp4", "and rtp4 have", "rtp4 have been", "shown to promote", "to promote cell", "promote cell surface", "cell surface expression", "surface expression of", "expression of the", "of the bitter", "the bitter taste", "bitter taste receptors", "receptors tas2rs", "tas2rs behrens", "behrens et al.", "et al. 2006", "al. 2006 .", "2006 . reep1", ". reep1 and", "reep1 and reep5", "reep5 also", "also known as", "known as dp1", "dp1 are", "are involved in", "involved in shaping", "in shaping the", "shaping the er", "the er by", "er by linking", "by linking microtubule", "linking microtubule fibers", "microtubule fibers to", "fibers to the", "to the er", "er park", "park et al.", "et al. 2010", "2010 voeltz", "voeltz et al.", "2006 . a", ". a recent", "a recent study", "recent study looking", "study looking at", "looking at the", "at the role", "the role of", "role of reep", "of reep in", "reep in the", "trafficking of alpha2a", "alpha2a and", "and alpha2c adrenergic", "alpha2c adrenergic receptors", "adrenergic receptors showed", "receptors showed that", "showed that reep1", "that reep1 2", "reep1 2 and", "2 and 6", "and 6 enhance", "6 enhance the", "enhance the cell", "expression of alpha2c", "alpha2c but", "but not alpha2a", "alpha2a by", "by increasing the", "increasing the capacity", "the capacity of", "capacity of er", "of er cargo", "cargo thereby", "thereby allowing more", "allowing more receptors", "more receptors to", "receptors to reach", "to reach the", "reach the cell", "surface bjork", "bjork et al.", "et al. 2013", "al. 2013 .", "2013 . unlike", ". unlike rtp1", "rtp1 reep1", "and 6 are", "6 are only", "are only present", "only present in", "present in the", "er do", "do not traffic", "not traffic to", "traffic to the", "plasma membrane and", "membrane and specifically", "and specifically interact", "specifically interact with", "interact with the", "with the minimal/non", "the minimal/non glycosylated", "minimal/non glycosylated forms", "glycosylated forms of", "forms of alpha2c", "of alpha2c via", "alpha2c via an", "via an interaction", "an interaction with", "interaction with its", "with its c", "its c terminus", "terminus saito", "2004 bjork", "2013 . reeps", ". reeps may", "reeps may function", "may function as", "function as general", "as general modulators", "general modulators of", "modulators of the", "of the er", "er rather", "rather than specifically", "than specifically interacting", "specifically interacting with", "interacting with gpcrs.", "with gpcrs. loss", "gpcrs. loss of", "loss of association", "of association of", "association of reep2", "of reep2 with", "reep2 with membranes", "with membranes leads", "membranes leads to", "leads to hereditary", "to hereditary spastic", "hereditary spastic paraplegia", "paraplegia esteves", "esteves et al.", "et al. 2014", "al. 2014 .
olfactory", "2014 .
olfactory receptors", "ors also", "called odorant receptors", "receptors are", "are present on", "present on the", "on the plasma", "plasma membrane of", "membrane of cilia", "of cilia of", "of olfactory sensory", "olfactory sensory neurons", "sensory neurons located", "neurons located in", "located in the", "the olfactory epithelium", "olfactory epithelium of", "epithelium of the", "of the nasal", "the nasal sinus.", "nasal sinus. each", "sinus. each mature", "each mature neuron", "mature neuron expresses", "neuron expresses only", "expresses only one", "only one or", "one or gene", "gene reviewed", "reviewed in nagai", "in nagai et", "nagai et al.", "et al. 2016", "2016 and", "and each or", "each or binds", "or binds one", "binds one particular", "one particular volatile", "particular volatile chemical", "volatile chemical or", "chemical or set", "or set of", "set of volatile", "of volatile chemicals", "chemicals known", "known as odorants.", "as odorants. the", "odorants. the binding", "the binding of", "binding of an", "of an odorant", "an odorant to", "odorant to an", "to an or", "or mainland", "mainland et al.", "et al. 2015", "2015 causes", "causes a conformational", "a conformational change", "conformational change in", "change in the", "in the receptor", "the receptor that", "receptor that activates", "that activates the", "activates the g", "the g alpha", "g alpha subunit", "subunit golf", "golf gnal", "gnal of", "of an associated", "an associated heterotrimeric", "associated heterotrimeric g", "g protein complex", "protein complex to", "complex to exchange", "to exchange gdp", "exchange gdp for", "gdp for gtp", "gtp inferred", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in jones", "in jones et", "jones et al.", "et al. 1990", "al. 1990 .", "1990 . gnal:gtp", ". gnal:gtp and", "gnal:gtp and the", "and the gbeta:ggamma", "the gbeta:ggamma subcomplex", "subcomplex gnb1:gng13", "gnb1:gng13 dissociate", "dissociate from the", "from the olfactory", "the olfactory receptor", "olfactory receptor and", "receptor and gnal:gtp", "and gnal:gtp then", "gnal:gtp then binds", "then binds and", "binds and activates", "and activates adenylate", "activates adenylate cyclase", "adenylate cyclase 3", "3 adcy3", "inferred from rat", "from rat homologs", "rat homologs in", "homologs in bakalyar", "in bakalyar and", "bakalyar and reed", "and reed 1990", "1990 reviewed", "reviewed in boccaccio", "in boccaccio et", "boccaccio et al.", "et al. 2021", "al. 2021 .", "2021 . cyclic", ". cyclic amp", "cyclic amp produced", "amp produced by", "produced by adcy3", "by adcy3 binds", "adcy3 binds and", "binds and opens", "and opens the", "opens the olfactory", "the olfactory cyclic", "olfactory cyclic nucleotide", "cyclic nucleotide gated", "nucleotide gated channel", "channel cng", "channel composed", "composed of cnga2", "cnga2 cnga4", "cnga4 and", "and cngb isoform", "cngb isoform 1b", "1b inferred", "homologs in liman", "in liman and", "liman and buck", "and buck 1994", "buck 1994 .", "1994 . the", ". the cng", "the cng channel", "cng channel translocates", "channel translocates sodium", "translocates sodium and", "sodium and calcium", "and calcium cations", "calcium cations from", "cations from the", "from the extracellular", "the extracellular region", "extracellular region into", "region into the", "into the cytosol.", "the cytosol. the", "cytosol. the resulting", "the resulting cytosolic", "resulting cytosolic calcium", "cytosolic calcium ions", "calcium ions bind", "ions bind ano2", "bind ano2 and", "ano2 and increase", "and increase the", "increase the transport", "transport of chloride", "of chloride ions", "chloride ions by", "ions by ano2", "by ano2 from", "ano2 from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the extracellular", "region inferred", "homologs in pifferi", "in pifferi et", "pifferi et al.", "et al. 2009", "2009 stephan", "stephan et al.", "al. 2009 .", "2009 . the", ". the translocations", "the translocations of", "translocations of ions", "of ions across", "ions across the", "across the plasma", "plasma membrane causes", "membrane causes depolarization", "causes depolarization of", "depolarization of the", "of the neuron", "the neuron yielding", "neuron yielding a", "yielding a receptor", "a receptor potential", "receptor potential and", "potential and action", "and action potential", "action potential that", "potential that is", "that is transmitted", "is transmitted to", "transmitted to the", "to the olfactory", "the olfactory bulb", "olfactory bulb of", "bulb of the", "of the brain.", "olfactory receptor or", "or also called", "also called odorant receptor", "odorant receptor genes", "receptor genes were", "genes were discovered in", "were discovered in rats", "discovered in rats by", "in rats by linda", "rats by linda buck", "by linda buck and", "linda buck and richard", "buck and richard axel", "richard axel who", "axel who predicted", "who predicted that odorants", "predicted that odorants would", "that odorants would be", "odorants would be detected", "would be detected by", "be detected by a", "detected by a large", "by a large family", "a large family of", "large family of g", "family of g protein", "of g protein coupled", "g protein coupled receptors", "coupled receptors gpcrs", "gpcrs that are", "that are selectively expressed", "are selectively expressed in", "selectively expressed in the", "expressed in the olfactory", "in the olfactory epithelium.", "the olfactory epithelium. this", "olfactory epithelium. this prediction", "epithelium. this prediction was", "this prediction was based", "prediction was based on", "was based on previous", "based on previous biochemical", "on previous biochemical evidence", "previous biochemical evidence that", "biochemical evidence that camp", "evidence that camp levels", "that camp levels increased", "camp levels increased in", "levels increased in olfactory", "increased in olfactory neurons", "in olfactory neurons upon", "olfactory neurons upon odor", "neurons upon odor stimulation.", "upon odor stimulation. these", "odor stimulation. these predictions", "stimulation. these predictions proved", "these predictions proved to", "predictions proved to be", "proved to be accurate", "be accurate and", "accurate and buck", "and buck and axel", "buck and axel received", "and axel received a", "axel received a nobel", "received a nobel prize", "a nobel prize for", "nobel prize for this", "prize for this and", "for this and subsequent", "this and subsequent work", "subsequent work reviewed", "work reviewed in", "reviewed in keller &", "in keller & vosshall", "keller & vosshall 2008", "& vosshall 2008 .
subsequent", "vosshall 2008 .
subsequent work", "2008 .
subsequent work in", ".
subsequent work in mice", "work in mice and", "in mice and other", "mice and other vertebrates", "and other vertebrates has", "other vertebrates has confirmed", "vertebrates has confirmed that", "has confirmed that or", "confirmed that or genes", "that or genes are", "or genes are comprised", "genes are comprised of", "are comprised of a", "comprised of a very", "of a very large", "a very large family", "very large family of", "selectively expressed in olfactory", "expressed in olfactory epithelium.", "in olfactory epithelium. although", "olfactory epithelium. although some", "epithelium. although some or", "although some or are", "some or are also", "or are also expressed", "are also expressed selectively", "also expressed selectively in", "expressed selectively in one", "selectively in one or", "in one or a", "one or a few", "or a few other", "a few other tissues", "other tissues their", "tissues their expression", "their expression in olfactory", "expression in olfactory epithelium", "in olfactory epithelium generally", "olfactory epithelium generally indicates", "epithelium generally indicates a", "generally indicates a functional", "indicates a functional role", "a functional role in", "functional role in mediating", "role in mediating olfaction", "mediating olfaction where", "olfaction where they", "where they couple binding", "they couple binding by", "couple binding by odorant", "binding by odorant ligands", "by odorant ligands with", "odorant ligands with intracellular", "ligands with intracellular olfactory", "with intracellular olfactory signaling.", "olfactory signaling. note:", "signaling. note: the", "note: the other subclasses", "the other subclasses of", "other subclasses of gpcr", "subclasses of gpcr signaling", "of gpcr signaling pathways", "gpcr signaling pathways are", "signaling pathways are described", "pathways are described under", "are described under \\gpcr", "described under \\gpcr signaling\\.", "under \\gpcr signaling\\.
the", "\\gpcr signaling\\.
the ligands", "signaling\\.
the ligands for", "
the ligands for ors", "ligands for ors are", "for ors are diverse", "are diverse ranging", "diverse ranging from", "ranging from chemical compounds", "from chemical compounds to", "chemical compounds to peptides.", "compounds to peptides. intracellular", "to peptides. intracellular signaling", "peptides. intracellular signaling by", "intracellular signaling by or", "signaling by or proteins", "by or proteins in", "or proteins in mice", "proteins in mice and", "mice and other mammalian", "and other mammalian systems", "other mammalian systems is", "mammalian systems is known", "systems is known to", "is known to be", "known to be mediated", "to be mediated via", "be mediated via direct", "mediated via direct interactions", "via direct interactions of", "direct interactions of or", "interactions of or proteins", "of or proteins with", "or proteins with an", "proteins with an olfactory", "with an olfactory specific", "an olfactory specific heterotrimeric", "olfactory specific heterotrimeric g", "specific heterotrimeric g protein", "g protein that", "protein that contains", "that contains an olfactory", "contains an olfactory specific", "an olfactory specific g", "olfactory specific g alpha", "specific g alpha protein:", "g alpha protein: g", "alpha protein: g alpha", "protein: g alpha s", "g alpha s olph", "s olph also", "olph also named", "also named \\gnal\\ .
in", "named \\gnal\\ .
in model", "\\gnal\\ .
in model genetic", ".
in model genetic systems", "model genetic systems such", "genetic systems such as", "systems such as mice", "as mice many", "mice many candidate", "many candidate or genes", "candidate or genes have", "or genes have been", "genes have been shown", "have been shown experimentally", "been shown experimentally to", "shown experimentally to function", "experimentally to function in", "to function in olfactory", "function in olfactory signaling", "olfactory signaling reviewed", "signaling reviewed in", "& vosshall 2008 .", "vosshall 2008 . for", "2008 . for the", ". for the human", "for the human or", "the human or genes", "or genes experimental", "genes experimental analysis", "experimental analysis has been", "analysis has been more", "has been more limited", "more limited although", "limited although some", "although some specific or", "some specific or genes", "or genes such", "genes such as", "such as or7d4 and", "as or7d4 and or11h7p", "or7d4 and or11h7p have", "and or11h7p have been", "or11h7p have been confirmed", "have been confirmed to", "been confirmed to mediate", "confirmed to mediate olfactory", "to mediate olfactory response", "mediate olfactory response and", "olfactory response and signaling", "response and signaling in", "and signaling in humans", "signaling in humans for", "in humans for specific", "humans for specific chemical", "for specific chemical odorants", "chemical odorants keller", "odorants keller et", "keller et al. 2007", "al. 2007 abbafy", "2007 abbafy 2007", "abbafy 2007 . mice", "2007 . mice and", ". mice and other", "mice and other rodents", "and other rodents are", "other rodents are believed", "rodents are believed to", "are believed to have", "believed to have about", "to have about 1000", "have about 1000 functional", "about 1000 functional or", "1000 functional or genes", "or genes as", "genes as well", "as well as many", "well as many additional", "as many additional pseudogenes.", "additional pseudogenes. based", "pseudogenes. based on", "based on sequence similarities", "sequence similarities there", "similarities there are", "there are 960 human", "are 960 human or", "960 human or genes", "or genes but", "genes but approximately", "but approximately half of", "approximately half of these", "half of these are", "of these are pseudogenes", "are pseudogenes keller", "pseudogenes keller 2008", "keller 2008 . in", "2008 . in mice", "in mice essentially", "mice essentially all", "essentially all olfactory signaling", "all olfactory signaling requires", "olfactory signaling requires g", "signaling requires g alpha", "requires g alpha s", "olf mouse", "mouse g olf knockouts", "g olf knockouts have", "olf knockouts have been", "knockouts have been shown", "have been shown to", "been shown to lack", "shown to lack olfactory", "to lack olfactory responses", "olfactory responses belluscio", "responses belluscio 1998", "belluscio 1998 . bona", "1998 . bona fide", ". bona fide human", "bona fide human or", "fide human or genes", "human or genes identified", "or genes identified by", "genes identified by sequence", "identified by sequence similarity", "sequence similarity not", "similarity not pseudogenes", "not pseudogenes with function", "pseudogenes with function blocking", "with function blocking mutations", "blocking mutations that", "mutations that are", "that are expressed in", "are expressed in olfactory", "expressed in olfactory epithelium", "in olfactory epithelium are", "olfactory epithelium are expected", "epithelium are expected to", "are expected to interact", "expected to interact with", "to interact with g", "interact with g alpha", "with g alpha s", "g alpha s olf", "alpha s olf containing", "s olf containing g", "olf containing g protein", "containing g protein trimers.", "g protein trimers.
of", "protein trimers.
of the", "trimers.
of the 960", "
of the 960 human", "the 960 human or", "human or genes and", "or genes and pseudogenes", "and pseudogenes there", "pseudogenes there is", "there is experimental evidence", "is experimental evidence that", "experimental evidence that indicates", "evidence that indicates over", "that indicates over 430", "indicates over 430 are", "over 430 are expressed", "430 are expressed in", "are expressed in human", "expressed in human olfactory", "in human olfactory epithelium", "olfactory epithelium including", "epithelium including 80", "including 80 expressed or", "80 expressed or pseudogenes", "or pseudogenes zhang", "pseudogenes zhang 2007", "zhang 2007 .
when expressed", "2007 .
when expressed in", ".
when expressed in model", "expressed in model cell", "in model cell systems", "model cell systems mammalian", "cell systems mammalian olfactory", "systems mammalian olfactory receptors", "olfactory receptors ors", "ors are typically", "are typically retained in", "typically retained in the", "retained in the er", "in the er and", "the er and degraded", "er and degraded by", "and degraded by the", "degraded by the proteasome", "the proteasome mcclintock", "proteasome mcclintock et", "mcclintock et al. 1997", "et al. 1997 .", "al. 1997 . a", "1997 . a study", ". a study using", "a study using caenorhabditis", "study using caenorhabditis elegans", "using caenorhabditis elegans showed", "caenorhabditis elegans showed that", "elegans showed that the", "showed that the transport", "that the transport of", "the transport of ors", "transport of ors to", "of ors to the", "ors to the cilia", "to the cilia of", "the cilia of olfactory", "cilia of olfactory neurons", "of olfactory neurons required", "olfactory neurons required the", "neurons required the expression", "required the expression and", "the expression and association", "expression and association of", "and association of ors", "association of ors with", "of ors with a", "ors with a transmembrane", "with a transmembrane protein", "transmembrane protein odr4", "odr4 dwyer et", "dwyer et al. 1998", "et al. 1998 .", "al. 1998 . co", "1998 . co transfection", ". co transfection of", "co transfection of rat", "transfection of rat ors", "of rat ors with", "rat ors with odr4", "ors with odr4 enhanced", "with odr4 enhanced the", "odr4 enhanced the transport", "enhanced the transport and", "the transport and expression", "transport and expression of", "and expression of ors", "expression of ors at", "of ors at the", "ors at the cell", "at the cell surface", "cell surface gimelbrant", "surface gimelbrant et", "gimelbrant et al. 2001", "et al. 2001 .", "al. 2001 . these", "2001 . these studies", ". these studies suggested", "these studies suggested that", "studies suggested that olfactory", "suggested that olfactory neurons", "that olfactory neurons might", "olfactory neurons might have", "neurons might have a", "might have a selective", "have a selective molecular", "a selective molecular machinery", "selective molecular machinery that", "molecular machinery that promotes", "machinery that promotes expression", "that promotes expression of", "promotes expression of ors", "ors at the cells", "at the cells surface.", "the cells surface. two", "cells surface. two human", "surface. two human protein", "two human protein families", "human protein families have", "protein families have been", "families have been identified", "have been identified as", "been identified as potential", "identified as potential accessory", "as potential accessory proteins", "potential accessory proteins involved", "accessory proteins involved in", "proteins involved in the", "involved in the trafficking", "in the trafficking of", "the trafficking of ors", "trafficking of ors to", "ors to the plasma", "to the plasma membrane", "plasma membrane saito", "membrane saito et", "saito et al. 2004", "et al. 2004 .", "al. 2004 . receptor", "2004 . receptor transporting", ". receptor transporting proteins", "receptor transporting proteins 1", "transporting proteins 1 and", "proteins 1 and 2", "and 2 rtp1", "rtp2 both strongly", "both strongly induced expression", "strongly induced expression of", "induced expression of several", "expression of several ors", "of several ors at", "several ors at the", "at the cell surface.", "the cell surface. to", "cell surface. to a", "surface. to a lesser", "to a lesser extent", "lesser extent the", "extent the receptor", "the receptor expression enhancing", "receptor expression enhancing protein", "expression enhancing protein 1", "protein 1 reep1", "reep1 also promoted", "also promoted cell surface", "promoted cell surface expression.", "cell surface expression. these", "surface expression. these proteins", "expression. these proteins are", "these proteins are specifically", "proteins are specifically expressed", "are specifically expressed in", "specifically expressed in olfactory", "expressed in olfactory neurons", "in olfactory neurons with", "olfactory neurons with no", "neurons with no expression", "with no expression in", "no expression in testis", "in testis where", "testis where a", "where a subset of", "a subset of ors", "subset of ors are", "of ors are expressed", "are expressed parmentier", "expressed parmentier et", "parmentier et al. 1992", "al. 1992 spehr", "1992 spehr et", "spehr et al. 2003", "et al. 2003 .", "al. 2003 . other", "2003 . other members", ". other members of", "other members of the", "members of the rtp", "of the rtp and", "the rtp and reep", "rtp and reep families", "and reep families have", "reep families have a", "families have a widespread", "have a widespread distribution.", "a widespread distribution. rtp3", "widespread distribution. rtp3 and", "distribution. rtp3 and rtp4", "rtp3 and rtp4 have", "and rtp4 have been", "rtp4 have been shown", "been shown to promote", "shown to promote cell", "to promote cell surface", "promote cell surface expression", "cell surface expression of", "surface expression of the", "expression of the bitter", "of the bitter taste", "the bitter taste receptors", "taste receptors tas2rs", "tas2rs behrens et", "behrens et al. 2006", "et al. 2006 .", "al. 2006 . reep1", "2006 . reep1 and", ". reep1 and reep5", "and reep5 also", "reep5 also known", "also known as dp1", "as dp1 are", "dp1 are involved", "are involved in shaping", "involved in shaping the", "in shaping the er", "shaping the er by", "the er by linking", "er by linking microtubule", "by linking microtubule fibers", "linking microtubule fibers to", "microtubule fibers to the", "fibers to the er", "the er park", "er park et", "park et al. 2010", "al. 2010 voeltz", "2010 voeltz et", "voeltz et al. 2006", "al. 2006 . a", "2006 . a recent", ". a recent study", "a recent study looking", "recent study looking at", "study looking at the", "looking at the role", "at the role of", "the role of reep", "role of reep in", "of reep in the", "reep in the trafficking", "the trafficking of alpha2a", "of alpha2a and", "alpha2a and alpha2c", "and alpha2c adrenergic receptors", "alpha2c adrenergic receptors showed", "adrenergic receptors showed that", "receptors showed that reep1", "showed that reep1 2", "that reep1 2 and", "reep1 2 and 6", "2 and 6 enhance", "and 6 enhance the", "6 enhance the cell", "enhance the cell surface", "the cell surface expression", "surface expression of alpha2c", "of alpha2c but", "alpha2c but not", "not alpha2a by", "alpha2a by increasing", "by increasing the capacity", "increasing the capacity of", "the capacity of er", "capacity of er cargo", "er cargo thereby", "cargo thereby allowing", "thereby allowing more receptors", "allowing more receptors to", "more receptors to reach", "receptors to reach the", "to reach the cell", "reach the cell surface", "cell surface bjork", "surface bjork et", "bjork et al. 2013", "et al. 2013 .", "al. 2013 . unlike", "2013 . unlike rtp1", "unlike rtp1 reep1", "rtp1 reep1 2", "2 and 6 are", "and 6 are only", "6 are only present", "are only present in", "only present in the", "present in the er", "the er do", "er do not", "do not traffic to", "not traffic to the", "traffic to the plasma", "the plasma membrane and", "plasma membrane and specifically", "membrane and specifically interact", "and specifically interact with", "specifically interact with the", "interact with the minimal/non", "with the minimal/non glycosylated", "the minimal/non glycosylated forms", "minimal/non glycosylated forms of", "glycosylated forms of alpha2c", "forms of alpha2c via", "of alpha2c via an", "alpha2c via an interaction", "via an interaction with", "an interaction with its", "interaction with its c", "with its c terminus", "c terminus saito", "terminus saito et", "al. 2004 bjork", "2004 bjork et", "al. 2013 . reeps", "2013 . reeps may", ". reeps may function", "reeps may function as", "may function as general", "function as general modulators", "as general modulators of", "general modulators of the", "modulators of the er", "the er rather", "er rather than", "rather than specifically interacting", "than specifically interacting with", "specifically interacting with gpcrs.", "interacting with gpcrs. loss", "with gpcrs. loss of", "gpcrs. loss of association", "loss of association of", "of association of reep2", "association of reep2 with", "of reep2 with membranes", "reep2 with membranes leads", "with membranes leads to", "membranes leads to hereditary", "leads to hereditary spastic", "to hereditary spastic paraplegia", "spastic paraplegia esteves", "paraplegia esteves et", "esteves et al. 2014", "et al. 2014 .
olfactory", "al. 2014 .
olfactory receptors", ".
olfactory receptors ors", "ors also called", "also called odorant receptors", "odorant receptors are", "receptors are present", "are present on the", "present on the plasma", "on the plasma membrane", "the plasma membrane of", "plasma membrane of cilia", "membrane of cilia of", "of cilia of olfactory", "cilia of olfactory sensory", "of olfactory sensory neurons", "olfactory sensory neurons located", "sensory neurons located in", "neurons located in the", "located in the olfactory", "in the olfactory epithelium", "the olfactory epithelium of", "olfactory epithelium of the", "epithelium of the nasal", "of the nasal sinus.", "the nasal sinus. each", "nasal sinus. each mature", "sinus. each mature neuron", "each mature neuron expresses", "mature neuron expresses only", "neuron expresses only one", "expresses only one or", "only one or gene", "or gene reviewed", "gene reviewed in", "reviewed in nagai et", "in nagai et al.", "nagai et al. 2016", "al. 2016 and", "2016 and each", "and each or binds", "each or binds one", "or binds one particular", "binds one particular volatile", "one particular volatile chemical", "particular volatile chemical or", "volatile chemical or set", "chemical or set of", "or set of volatile", "set of volatile chemicals", "volatile chemicals known", "chemicals known as", "known as odorants. the", "as odorants. the binding", "odorants. the binding of", "the binding of an", "binding of an odorant", "of an odorant to", "an odorant to an", "odorant to an or", "an or mainland", "or mainland et", "mainland et al. 2015", "al. 2015 causes", "2015 causes a", "causes a conformational change", "a conformational change in", "conformational change in the", "change in the receptor", "in the receptor that", "the receptor that activates", "receptor that activates the", "that activates the g", "activates the g alpha", "the g alpha subunit", "alpha subunit golf", "gnal of an", "of an associated heterotrimeric", "an associated heterotrimeric g", "associated heterotrimeric g protein", "heterotrimeric g protein complex", "g protein complex to", "protein complex to exchange", "complex to exchange gdp", "to exchange gdp for", "exchange gdp for gtp", "for gtp inferred", "gtp inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in jones", "homologs in jones et", "in jones et al.", "jones et al. 1990", "et al. 1990 .", "al. 1990 . gnal:gtp", "1990 . gnal:gtp and", ". gnal:gtp and the", "gnal:gtp and the gbeta:ggamma", "and the gbeta:ggamma subcomplex", "gbeta:ggamma subcomplex gnb1:gng13", "gnb1:gng13 dissociate from", "dissociate from the olfactory", "from the olfactory receptor", "the olfactory receptor and", "olfactory receptor and gnal:gtp", "receptor and gnal:gtp then", "and gnal:gtp then binds", "gnal:gtp then binds and", "then binds and activates", "binds and activates adenylate", "and activates adenylate cyclase", "activates adenylate cyclase 3", "cyclase 3 adcy3", "adcy3 inferred", "inferred from rat homologs", "from rat homologs in", "rat homologs in bakalyar", "homologs in bakalyar and", "in bakalyar and reed", "bakalyar and reed 1990", "reed 1990 reviewed", "1990 reviewed in", "reviewed in boccaccio et", "in boccaccio et al.", "boccaccio et al. 2021", "et al. 2021 .", "al. 2021 . cyclic", "2021 . cyclic amp", ". cyclic amp produced", "cyclic amp produced by", "amp produced by adcy3", "produced by adcy3 binds", "by adcy3 binds and", "adcy3 binds and opens", "binds and opens the", "and opens the olfactory", "opens the olfactory cyclic", "the olfactory cyclic nucleotide", "olfactory cyclic nucleotide gated", "cyclic nucleotide gated channel", "gated channel cng", "channel cng channel", "cng channel composed", "channel composed of", "of cnga2 cnga4", "cnga4 and cngb", "and cngb isoform 1b", "isoform 1b inferred", "1b inferred from", "rat homologs in liman", "homologs in liman and", "in liman and buck", "liman and buck 1994", "and buck 1994 .", "buck 1994 . the", "1994 . the cng", ". the cng channel", "the cng channel translocates", "cng channel translocates sodium", "channel translocates sodium and", "translocates sodium and calcium", "sodium and calcium cations", "and calcium cations from", "calcium cations from the", "cations from the extracellular", "from the extracellular region", "the extracellular region into", "extracellular region into the", "region into the cytosol.", "into the cytosol. the", "the cytosol. the resulting", "cytosol. the resulting cytosolic", "the resulting cytosolic calcium", "resulting cytosolic calcium ions", "cytosolic calcium ions bind", "calcium ions bind ano2", "ions bind ano2 and", "bind ano2 and increase", "ano2 and increase the", "and increase the transport", "increase the transport of", "the transport of chloride", "transport of chloride ions", "of chloride ions by", "chloride ions by ano2", "ions by ano2 from", "by ano2 from the", "ano2 from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the extracellular", "to the extracellular region", "extracellular region inferred", "region inferred from", "mouse homologs in pifferi", "homologs in pifferi et", "in pifferi et al.", "pifferi et al. 2009", "al. 2009 stephan", "2009 stephan et", "stephan et al. 2009", "et al. 2009 .", "al. 2009 . the", "2009 . the translocations", ". the translocations of", "the translocations of ions", "translocations of ions across", "of ions across the", "ions across the plasma", "across the plasma membrane", "the plasma membrane causes", "plasma membrane causes depolarization", "membrane causes depolarization of", "causes depolarization of the", "depolarization of the neuron", "of the neuron yielding", "the neuron yielding a", "neuron yielding a receptor", "yielding a receptor potential", "a receptor potential and", "receptor potential and action", "potential and action potential", "and action potential that", "action potential that is", "potential that is transmitted", "that is transmitted to", "is transmitted to the", "transmitted to the olfactory", "to the olfactory bulb", "the olfactory bulb of", "olfactory bulb of the", "bulb of the brain.", "mammalian olfactory receptor or", "receptor or also", "or also called odorant", "called odorant receptor genes", "odorant receptor genes were", "receptor genes were discovered", "genes were discovered in rats", "were discovered in rats by", "discovered in rats by linda", "in rats by linda buck", "rats by linda buck and", "by linda buck and richard", "linda buck and richard axel", "and richard axel who", "richard axel who predicted", "axel who predicted that", "who predicted that odorants would", "predicted that odorants would be", "that odorants would be detected", "odorants would be detected by", "would be detected by a", "be detected by a large", "detected by a large family", "by a large family of", "a large family of g", "large family of g protein", "family of g protein coupled", "of g protein coupled receptors", "protein coupled receptors gpcrs", "receptors gpcrs that", "gpcrs that are selectively", "that are selectively expressed in", "are selectively expressed in the", "selectively expressed in the olfactory", "expressed in the olfactory epithelium.", "in the olfactory epithelium. this", "the olfactory epithelium. this prediction", "olfactory epithelium. this prediction was", "epithelium. this prediction was based", "this prediction was based on", "prediction was based on previous", "was based on previous biochemical", "based on previous biochemical evidence", "on previous biochemical evidence that", "previous biochemical evidence that camp", "biochemical evidence that camp levels", "evidence that camp levels increased", "that camp levels increased in", "camp levels increased in olfactory", "levels increased in olfactory neurons", "increased in olfactory neurons upon", "in olfactory neurons upon odor", "olfactory neurons upon odor stimulation.", "neurons upon odor stimulation. these", "upon odor stimulation. these predictions", "odor stimulation. these predictions proved", "stimulation. these predictions proved to", "these predictions proved to be", "predictions proved to be accurate", "to be accurate and", "be accurate and buck", "accurate and buck and", "and buck and axel received", "buck and axel received a", "and axel received a nobel", "axel received a nobel prize", "received a nobel prize for", "a nobel prize for this", "nobel prize for this and", "prize for this and subsequent", "for this and subsequent work", "and subsequent work reviewed", "subsequent work reviewed in", "work reviewed in keller", "reviewed in keller & vosshall", "in keller & vosshall 2008", "keller & vosshall 2008 .
subsequent", "& vosshall 2008 .
subsequent work", "vosshall 2008 .
subsequent work in", "2008 .
subsequent work in mice", ".
subsequent work in mice and", "work in mice and other", "in mice and other vertebrates", "mice and other vertebrates has", "and other vertebrates has confirmed", "other vertebrates has confirmed that", "vertebrates has confirmed that or", "has confirmed that or genes", "confirmed that or genes are", "that or genes are comprised", "or genes are comprised of", "genes are comprised of a", "are comprised of a very", "comprised of a very large", "of a very large family", "a very large family of", "very large family of g", "are selectively expressed in olfactory", "selectively expressed in olfactory epithelium.", "expressed in olfactory epithelium. although", "in olfactory epithelium. although some", "olfactory epithelium. although some or", "epithelium. although some or are", "although some or are also", "some or are also expressed", "or are also expressed selectively", "are also expressed selectively in", "also expressed selectively in one", "expressed selectively in one or", "selectively in one or a", "in one or a few", "one or a few other", "or a few other tissues", "few other tissues their", "other tissues their expression", "tissues their expression in", "their expression in olfactory epithelium", "expression in olfactory epithelium generally", "in olfactory epithelium generally indicates", "olfactory epithelium generally indicates a", "epithelium generally indicates a functional", "generally indicates a functional role", "indicates a functional role in", "a functional role in mediating", "functional role in mediating olfaction", "in mediating olfaction where", "mediating olfaction where they", "olfaction where they couple", "where they couple binding by", "they couple binding by odorant", "couple binding by odorant ligands", "binding by odorant ligands with", "by odorant ligands with intracellular", "odorant ligands with intracellular olfactory", "ligands with intracellular olfactory signaling.", "intracellular olfactory signaling. note:", "olfactory signaling. note: the", "signaling. note: the other", "note: the other subclasses of", "the other subclasses of gpcr", "other subclasses of gpcr signaling", "subclasses of gpcr signaling pathways", "of gpcr signaling pathways are", "gpcr signaling pathways are described", "signaling pathways are described under", "pathways are described under \\gpcr", "are described under \\gpcr signaling\\.", "described under \\gpcr signaling\\.
the", "under \\gpcr signaling\\.
the ligands", "\\gpcr signaling\\.
the ligands for", "signaling\\.
the ligands for ors", "
the ligands for ors are", "ligands for ors are diverse", "ors are diverse ranging", "are diverse ranging from", "diverse ranging from chemical", "ranging from chemical compounds to", "from chemical compounds to peptides.", "chemical compounds to peptides. intracellular", "compounds to peptides. intracellular signaling", "to peptides. intracellular signaling by", "peptides. intracellular signaling by or", "intracellular signaling by or proteins", "signaling by or proteins in", "by or proteins in mice", "or proteins in mice and", "proteins in mice and other", "in mice and other mammalian", "mice and other mammalian systems", "and other mammalian systems is", "other mammalian systems is known", "mammalian systems is known to", "systems is known to be", "is known to be mediated", "known to be mediated via", "to be mediated via direct", "be mediated via direct interactions", "mediated via direct interactions of", "via direct interactions of or", "direct interactions of or proteins", "interactions of or proteins with", "of or proteins with an", "or proteins with an olfactory", "proteins with an olfactory specific", "with an olfactory specific heterotrimeric", "an olfactory specific heterotrimeric g", "olfactory specific heterotrimeric g protein", "heterotrimeric g protein that", "g protein that contains", "protein that contains an", "that contains an olfactory specific", "contains an olfactory specific g", "an olfactory specific g alpha", "olfactory specific g alpha protein:", "specific g alpha protein: g", "g alpha protein: g alpha", "alpha protein: g alpha s", "protein: g alpha s olph", "alpha s olph also", "s olph also named", "olph also named \\gnal\\", "also named \\gnal\\ .
in model", "named \\gnal\\ .
in model genetic", "\\gnal\\ .
in model genetic systems", ".
in model genetic systems such", "model genetic systems such as", "genetic systems such as mice", "such as mice many", "as mice many candidate", "mice many candidate or", "many candidate or genes have", "candidate or genes have been", "or genes have been shown", "genes have been shown experimentally", "have been shown experimentally to", "been shown experimentally to function", "shown experimentally to function in", "experimentally to function in olfactory", "to function in olfactory signaling", "in olfactory signaling reviewed", "olfactory signaling reviewed in", "keller & vosshall 2008 .", "& vosshall 2008 . for", "vosshall 2008 . for the", "2008 . for the human", ". for the human or", "for the human or genes", "human or genes experimental", "or genes experimental analysis", "genes experimental analysis has", "experimental analysis has been more", "analysis has been more limited", "been more limited although", "more limited although some", "limited although some specific", "although some specific or genes", "specific or genes such", "or genes such as", "genes such as or7d4", "such as or7d4 and or11h7p", "as or7d4 and or11h7p have", "or7d4 and or11h7p have been", "and or11h7p have been confirmed", "or11h7p have been confirmed to", "have been confirmed to mediate", "been confirmed to mediate olfactory", "confirmed to mediate olfactory response", "to mediate olfactory response and", "mediate olfactory response and signaling", "olfactory response and signaling in", "response and signaling in humans", "and signaling in humans for", "signaling in humans for specific", "in humans for specific chemical", "humans for specific chemical odorants", "specific chemical odorants keller", "chemical odorants keller et", "odorants keller et al.", "et al. 2007 abbafy", "al. 2007 abbafy 2007", "2007 abbafy 2007 .", "abbafy 2007 . mice and", "2007 . mice and other", ". mice and other rodents", "mice and other rodents are", "and other rodents are believed", "other rodents are believed to", "rodents are believed to have", "are believed to have about", "believed to have about 1000", "to have about 1000 functional", "have about 1000 functional or", "about 1000 functional or genes", "functional or genes as", "or genes as well", "genes as well as", "as well as many additional", "well as many additional pseudogenes.", "many additional pseudogenes. based", "additional pseudogenes. based on", "pseudogenes. based on sequence", "on sequence similarities there", "sequence similarities there are", "similarities there are 960", "there are 960 human or", "are 960 human or genes", "human or genes but", "or genes but approximately", "genes but approximately half", "but approximately half of these", "approximately half of these are", "half of these are pseudogenes", "these are pseudogenes keller", "are pseudogenes keller 2008", "pseudogenes keller 2008 .", "keller 2008 . in mice", ". in mice essentially", "in mice essentially all", "mice essentially all olfactory", "essentially all olfactory signaling requires", "all olfactory signaling requires g", "olfactory signaling requires g alpha", "signaling requires g alpha s", "olf mouse g", "mouse g olf knockouts have", "g olf knockouts have been", "olf knockouts have been shown", "knockouts have been shown to", "have been shown to lack", "been shown to lack olfactory", "shown to lack olfactory responses", "lack olfactory responses belluscio", "olfactory responses belluscio 1998", "responses belluscio 1998 .", "belluscio 1998 . bona fide", "1998 . bona fide human", ". bona fide human or", "bona fide human or genes", "fide human or genes identified", "human or genes identified by", "or genes identified by sequence", "genes identified by sequence similarity", "by sequence similarity not", "sequence similarity not pseudogenes", "similarity not pseudogenes with", "not pseudogenes with function blocking", "pseudogenes with function blocking mutations", "function blocking mutations that", "blocking mutations that are", "mutations that are expressed", "that are expressed in olfactory", "are expressed in olfactory epithelium", "expressed in olfactory epithelium are", "in olfactory epithelium are expected", "olfactory epithelium are expected to", "epithelium are expected to interact", "are expected to interact with", "expected to interact with g", "to interact with g alpha", "interact with g alpha s", "with g alpha s olf", "g alpha s olf containing", "alpha s olf containing g", "s olf containing g protein", "olf containing g protein trimers.", "containing g protein trimers.
of", "g protein trimers.
of the", "protein trimers.
of the 960", "trimers.
of the 960 human", "
of the 960 human or", "the 960 human or genes", "960 human or genes and", "human or genes and pseudogenes", "genes and pseudogenes there", "and pseudogenes there is", "pseudogenes there is experimental", "there is experimental evidence that", "is experimental evidence that indicates", "experimental evidence that indicates over", "evidence that indicates over 430", "that indicates over 430 are", "indicates over 430 are expressed", "over 430 are expressed in", "430 are expressed in human", "are expressed in human olfactory", "expressed in human olfactory epithelium", "human olfactory epithelium including", "olfactory epithelium including 80", "epithelium including 80 expressed", "including 80 expressed or pseudogenes", "expressed or pseudogenes zhang", "or pseudogenes zhang 2007", "pseudogenes zhang 2007 .
when", "zhang 2007 .
when expressed in", "2007 .
when expressed in model", ".
when expressed in model cell", "expressed in model cell systems", "in model cell systems mammalian", "model cell systems mammalian olfactory", "cell systems mammalian olfactory receptors", "mammalian olfactory receptors ors", "receptors ors are", "ors are typically retained", "are typically retained in the", "typically retained in the er", "retained in the er and", "in the er and degraded", "the er and degraded by", "er and degraded by the", "and degraded by the proteasome", "by the proteasome mcclintock", "the proteasome mcclintock et", "proteasome mcclintock et al.", "mcclintock et al. 1997 .", "et al. 1997 . a", "al. 1997 . a study", "1997 . a study using", ". a study using caenorhabditis", "a study using caenorhabditis elegans", "study using caenorhabditis elegans showed", "using caenorhabditis elegans showed that", "caenorhabditis elegans showed that the", "elegans showed that the transport", "showed that the transport of", "that the transport of ors", "the transport of ors to", "transport of ors to the", "of ors to the cilia", "ors to the cilia of", "to the cilia of olfactory", "the cilia of olfactory neurons", "cilia of olfactory neurons required", "of olfactory neurons required the", "olfactory neurons required the expression", "neurons required the expression and", "required the expression and association", "the expression and association of", "expression and association of ors", "and association of ors with", "association of ors with a", "of ors with a transmembrane", "ors with a transmembrane protein", "a transmembrane protein odr4", "protein odr4 dwyer", "odr4 dwyer et al.", "dwyer et al. 1998 .", "et al. 1998 . co", "al. 1998 . co transfection", "1998 . co transfection of", ". co transfection of rat", "co transfection of rat ors", "transfection of rat ors with", "of rat ors with odr4", "rat ors with odr4 enhanced", "ors with odr4 enhanced the", "with odr4 enhanced the transport", "odr4 enhanced the transport and", "enhanced the transport and expression", "the transport and expression of", "transport and expression of ors", "and expression of ors at", "expression of ors at the", "of ors at the cell", "ors at the cell surface", "the cell surface gimelbrant", "cell surface gimelbrant et", "surface gimelbrant et al.", "gimelbrant et al. 2001 .", "et al. 2001 . these", "al. 2001 . these studies", "2001 . these studies suggested", ". these studies suggested that", "these studies suggested that olfactory", "studies suggested that olfactory neurons", "suggested that olfactory neurons might", "that olfactory neurons might have", "olfactory neurons might have a", "neurons might have a selective", "might have a selective molecular", "have a selective molecular machinery", "a selective molecular machinery that", "selective molecular machinery that promotes", "molecular machinery that promotes expression", "machinery that promotes expression of", "that promotes expression of ors", "promotes expression of ors at", "of ors at the cells", "ors at the cells surface.", "at the cells surface. two", "the cells surface. two human", "cells surface. two human protein", "surface. two human protein families", "two human protein families have", "human protein families have been", "protein families have been identified", "families have been identified as", "have been identified as potential", "been identified as potential accessory", "identified as potential accessory proteins", "as potential accessory proteins involved", "potential accessory proteins involved in", "accessory proteins involved in the", "proteins involved in the trafficking", "involved in the trafficking of", "in the trafficking of ors", "the trafficking of ors to", "trafficking of ors to the", "of ors to the plasma", "ors to the plasma membrane", "the plasma membrane saito", "plasma membrane saito et", "membrane saito et al.", "saito et al. 2004 .", "et al. 2004 . receptor", "al. 2004 . receptor transporting", "2004 . receptor transporting proteins", ". receptor transporting proteins 1", "receptor transporting proteins 1 and", "transporting proteins 1 and 2", "1 and 2 rtp1", "2 rtp1 rtp2", "rtp1 rtp2 both", "rtp2 both strongly induced", "both strongly induced expression of", "strongly induced expression of several", "induced expression of several ors", "expression of several ors at", "of several ors at the", "several ors at the cell", "ors at the cell surface.", "at the cell surface. to", "the cell surface. to a", "cell surface. to a lesser", "surface. to a lesser extent", "a lesser extent the", "lesser extent the receptor", "extent the receptor expression", "the receptor expression enhancing protein", "receptor expression enhancing protein 1", "enhancing protein 1 reep1", "1 reep1 also", "reep1 also promoted cell", "also promoted cell surface expression.", "promoted cell surface expression. these", "cell surface expression. these proteins", "surface expression. these proteins are", "expression. these proteins are specifically", "these proteins are specifically expressed", "proteins are specifically expressed in", "are specifically expressed in olfactory", "specifically expressed in olfactory neurons", "expressed in olfactory neurons with", "in olfactory neurons with no", "olfactory neurons with no expression", "neurons with no expression in", "with no expression in testis", "expression in testis where", "in testis where a", "testis where a subset", "where a subset of ors", "a subset of ors are", "subset of ors are expressed", "ors are expressed parmentier", "are expressed parmentier et", "expressed parmentier et al.", "et al. 1992 spehr", "al. 1992 spehr et", "1992 spehr et al.", "spehr et al. 2003 .", "et al. 2003 . other", "al. 2003 . other members", "2003 . other members of", ". other members of the", "other members of the rtp", "members of the rtp and", "of the rtp and reep", "the rtp and reep families", "rtp and reep families have", "and reep families have a", "reep families have a widespread", "families have a widespread distribution.", "have a widespread distribution. rtp3", "a widespread distribution. rtp3 and", "widespread distribution. rtp3 and rtp4", "distribution. rtp3 and rtp4 have", "rtp3 and rtp4 have been", "and rtp4 have been shown", "rtp4 have been shown to", "have been shown to promote", "been shown to promote cell", "shown to promote cell surface", "to promote cell surface expression", "promote cell surface expression of", "cell surface expression of the", "surface expression of the bitter", "expression of the bitter taste", "of the bitter taste receptors", "bitter taste receptors tas2rs", "receptors tas2rs behrens", "tas2rs behrens et al.", "behrens et al. 2006 .", "et al. 2006 . reep1", "al. 2006 . reep1 and", "2006 . reep1 and reep5", "reep1 and reep5 also", "and reep5 also known", "reep5 also known as", "known as dp1 are", "as dp1 are involved", "dp1 are involved in", "are involved in shaping the", "involved in shaping the er", "in shaping the er by", "shaping the er by linking", "the er by linking microtubule", "er by linking microtubule fibers", "by linking microtubule fibers to", "linking microtubule fibers to the", "microtubule fibers to the er", "to the er park", "the er park et", "er park et al.", "et al. 2010 voeltz", "al. 2010 voeltz et", "2010 voeltz et al.", "voeltz et al. 2006 .", "et al. 2006 . a", "al. 2006 . a recent", "2006 . a recent study", ". a recent study looking", "a recent study looking at", "recent study looking at the", "study looking at the role", "looking at the role of", "at the role of reep", "the role of reep in", "role of reep in the", "of reep in the trafficking", "reep in the trafficking of", "in the trafficking of alpha2a", "trafficking of alpha2a and", "of alpha2a and alpha2c", "alpha2a and alpha2c adrenergic", "and alpha2c adrenergic receptors showed", "alpha2c adrenergic receptors showed that", "adrenergic receptors showed that reep1", "receptors showed that reep1 2", "showed that reep1 2 and", "that reep1 2 and 6", "reep1 2 and 6 enhance", "2 and 6 enhance the", "and 6 enhance the cell", "6 enhance the cell surface", "enhance the cell surface expression", "the cell surface expression of", "cell surface expression of alpha2c", "expression of alpha2c but", "of alpha2c but not", "alpha2c but not alpha2a", "but not alpha2a by", "not alpha2a by increasing", "alpha2a by increasing the", "by increasing the capacity of", "increasing the capacity of er", "the capacity of er cargo", "of er cargo thereby", "er cargo thereby allowing", "cargo thereby allowing more", "thereby allowing more receptors to", "allowing more receptors to reach", "more receptors to reach the", "receptors to reach the cell", "to reach the cell surface", "the cell surface bjork", "cell surface bjork et", "surface bjork et al.", "bjork et al. 2013 .", "et al. 2013 . unlike", "al. 2013 . unlike rtp1", ". unlike rtp1 reep1", "unlike rtp1 reep1 2", "rtp1 reep1 2 and", "reep1 2 and 6 are", "2 and 6 are only", "and 6 are only present", "6 are only present in", "are only present in the", "only present in the er", "in the er do", "the er do not", "er do not traffic", "do not traffic to the", "not traffic to the plasma", "traffic to the plasma membrane", "to the plasma membrane and", "the plasma membrane and specifically", "plasma membrane and specifically interact", "membrane and specifically interact with", "and specifically interact with the", "specifically interact with the minimal/non", "interact with the minimal/non glycosylated", "with the minimal/non glycosylated forms", "the minimal/non glycosylated forms of", "minimal/non glycosylated forms of alpha2c", "glycosylated forms of alpha2c via", "forms of alpha2c via an", "of alpha2c via an interaction", "alpha2c via an interaction with", "via an interaction with its", "an interaction with its c", "interaction with its c terminus", "its c terminus saito", "c terminus saito et", "terminus saito et al.", "et al. 2004 bjork", "al. 2004 bjork et", "2004 bjork et al.", "et al. 2013 . reeps", "al. 2013 . reeps may", "2013 . reeps may function", ". reeps may function as", "reeps may function as general", "may function as general modulators", "function as general modulators of", "as general modulators of the", "general modulators of the er", "of the er rather", "the er rather than", "er rather than specifically", "rather than specifically interacting with", "than specifically interacting with gpcrs.", "specifically interacting with gpcrs. loss", "interacting with gpcrs. loss of", "with gpcrs. loss of association", "gpcrs. loss of association of", "loss of association of reep2", "of association of reep2 with", "association of reep2 with membranes", "of reep2 with membranes leads", "reep2 with membranes leads to", "with membranes leads to hereditary", "membranes leads to hereditary spastic", "leads to hereditary spastic paraplegia", "hereditary spastic paraplegia esteves", "spastic paraplegia esteves et", "paraplegia esteves et al.", "esteves et al. 2014 .
olfactory", "et al. 2014 .
olfactory receptors", "2014 .
olfactory receptors ors", "receptors ors also", "ors also called odorant", "called odorant receptors are", "odorant receptors are present", "receptors are present on", "are present on the plasma", "present on the plasma membrane", "on the plasma membrane of", "the plasma membrane of cilia", "plasma membrane of cilia of", "membrane of cilia of olfactory", "of cilia of olfactory sensory", "cilia of olfactory sensory neurons", "of olfactory sensory neurons located", "olfactory sensory neurons located in", "sensory neurons located in the", "neurons located in the olfactory", "located in the olfactory epithelium", "in the olfactory epithelium of", "the olfactory epithelium of the", "olfactory epithelium of the nasal", "epithelium of the nasal sinus.", "of the nasal sinus. each", "the nasal sinus. each mature", "nasal sinus. each mature neuron", "sinus. each mature neuron expresses", "each mature neuron expresses only", "mature neuron expresses only one", "neuron expresses only one or", "expresses only one or gene", "one or gene reviewed", "or gene reviewed in", "gene reviewed in nagai", "reviewed in nagai et al.", "in nagai et al. 2016", "et al. 2016 and", "al. 2016 and each", "2016 and each or", "and each or binds one", "each or binds one particular", "or binds one particular volatile", "binds one particular volatile chemical", "one particular volatile chemical or", "particular volatile chemical or set", "volatile chemical or set of", "chemical or set of volatile", "or set of volatile chemicals", "of volatile chemicals known", "volatile chemicals known as", "chemicals known as odorants.", "known as odorants. the binding", "as odorants. the binding of", "odorants. the binding of an", "the binding of an odorant", "binding of an odorant to", "of an odorant to an", "an odorant to an or", "to an or mainland", "an or mainland et", "or mainland et al.", "et al. 2015 causes", "al. 2015 causes a", "2015 causes a conformational", "causes a conformational change in", "a conformational change in the", "conformational change in the receptor", "change in the receptor that", "in the receptor that activates", "the receptor that activates the", "receptor that activates the g", "that activates the g alpha", "activates the g alpha subunit", "g alpha subunit golf", "subunit golf gnal", "golf gnal of", "gnal of an associated", "of an associated heterotrimeric g", "an associated heterotrimeric g protein", "associated heterotrimeric g protein complex", "heterotrimeric g protein complex to", "g protein complex to exchange", "protein complex to exchange gdp", "complex to exchange gdp for", "to exchange gdp for gtp", "gdp for gtp inferred", "for gtp inferred from", "gtp inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in jones", "mouse homologs in jones et", "homologs in jones et al.", "in jones et al. 1990", "jones et al. 1990 .", "et al. 1990 . gnal:gtp", "al. 1990 . gnal:gtp and", "1990 . gnal:gtp and the", ". gnal:gtp and the gbeta:ggamma", "gnal:gtp and the gbeta:ggamma subcomplex", "the gbeta:ggamma subcomplex gnb1:gng13", "subcomplex gnb1:gng13 dissociate", "gnb1:gng13 dissociate from the", "dissociate from the olfactory receptor", "from the olfactory receptor and", "the olfactory receptor and gnal:gtp", "olfactory receptor and gnal:gtp then", "receptor and gnal:gtp then binds", "and gnal:gtp then binds and", "gnal:gtp then binds and activates", "then binds and activates adenylate", "binds and activates adenylate cyclase", "and activates adenylate cyclase 3", "adenylate cyclase 3 adcy3", "adcy3 inferred from", "inferred from rat homologs in", "from rat homologs in bakalyar", "rat homologs in bakalyar and", "homologs in bakalyar and reed", "in bakalyar and reed 1990", "and reed 1990 reviewed", "reed 1990 reviewed in", "1990 reviewed in boccaccio", "reviewed in boccaccio et al.", "in boccaccio et al. 2021", "boccaccio et al. 2021 .", "et al. 2021 . cyclic", "al. 2021 . cyclic amp", "2021 . cyclic amp produced", ". cyclic amp produced by", "cyclic amp produced by adcy3", "amp produced by adcy3 binds", "produced by adcy3 binds and", "by adcy3 binds and opens", "adcy3 binds and opens the", "binds and opens the olfactory", "and opens the olfactory cyclic", "opens the olfactory cyclic nucleotide", "the olfactory cyclic nucleotide gated", "olfactory cyclic nucleotide gated channel", "nucleotide gated channel cng", "gated channel cng channel", "cng channel composed of", "channel composed of cnga2", "composed of cnga2 cnga4", "cnga2 cnga4 and", "cnga4 and cngb isoform", "cngb isoform 1b inferred", "isoform 1b inferred from", "1b inferred from rat", "from rat homologs in liman", "rat homologs in liman and", "homologs in liman and buck", "in liman and buck 1994", "liman and buck 1994 .", "and buck 1994 . the", "buck 1994 . the cng", "1994 . the cng channel", ". the cng channel translocates", "the cng channel translocates sodium", "cng channel translocates sodium and", "channel translocates sodium and calcium", "translocates sodium and calcium cations", "sodium and calcium cations from", "and calcium cations from the", "calcium cations from the extracellular", "cations from the extracellular region", "from the extracellular region into", "the extracellular region into the", "extracellular region into the cytosol.", "region into the cytosol. the", "into the cytosol. the resulting", "the cytosol. the resulting cytosolic", "cytosol. the resulting cytosolic calcium", "the resulting cytosolic calcium ions", "resulting cytosolic calcium ions bind", "cytosolic calcium ions bind ano2", "calcium ions bind ano2 and", "ions bind ano2 and increase", "bind ano2 and increase the", "ano2 and increase the transport", "and increase the transport of", "increase the transport of chloride", "the transport of chloride ions", "transport of chloride ions by", "of chloride ions by ano2", "chloride ions by ano2 from", "ions by ano2 from the", "by ano2 from the cytosol", "ano2 from the cytosol to", "from the cytosol to the", "the cytosol to the extracellular", "cytosol to the extracellular region", "the extracellular region inferred", "extracellular region inferred from", "region inferred from mouse", "from mouse homologs in pifferi", "mouse homologs in pifferi et", "homologs in pifferi et al.", "in pifferi et al. 2009", "et al. 2009 stephan", "al. 2009 stephan et", "2009 stephan et al.", "stephan et al. 2009 .", "et al. 2009 . the", "al. 2009 . the translocations", "2009 . the translocations of", ". the translocations of ions", "the translocations of ions across", "translocations of ions across the", "of ions across the plasma", "ions across the plasma membrane", "across the plasma membrane causes", "the plasma membrane causes depolarization", "plasma membrane causes depolarization of", "membrane causes depolarization of the", "causes depolarization of the neuron", "depolarization of the neuron yielding", "of the neuron yielding a", "the neuron yielding a receptor", "neuron yielding a receptor potential", "yielding a receptor potential and", "a receptor potential and action", "receptor potential and action potential", "potential and action potential that", "and action potential that is", "action potential that is transmitted", "potential that is transmitted to", "that is transmitted to the", "is transmitted to the olfactory", "transmitted to the olfactory bulb", "to the olfactory bulb of", "the olfactory bulb of the", "olfactory bulb of the brain." ] }, { "record_id": "GLY_000594_1_305", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "381771", "r hsa", "hsa 381771", "r hsa 381771" ] }, { "record_id": "GLY_000594_1_305", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "and inactivation", "inactivation of", "of glucagon", "glucagon like", "like peptide", "peptide 1", "glp 1", "synthesis secretion", "secretion and", "and inactivation of", "inactivation of glucagon", 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which", "peptidase iv which cleaves", "iv which cleaves 2", "which cleaves 2 amino acids", "cleaves 2 amino acids at", "2 amino acids at the", "amino acids at the amino", "acids at the amino terminus", "at the amino terminus of", "the amino terminus of glp", "amino terminus of glp 1", "of glp 1 rendering", "glp 1 rendering it", "1 rendering it biologically" ] }, { "record_id": "GLY_000594_1_306", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "382556", "r hsa", "hsa 382556", "r hsa 382556" ] }, { "record_id": "GLY_000594_1_306", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "abc family", "family proteins", "proteins mediated", "mediated transport", "abc family proteins", "family proteins mediated", "proteins mediated transport", "abc family proteins mediated", "family proteins mediated transport", "abc family proteins mediated transport", "the atp", "atp binding", "binding cassette", 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defined", "associated with a defined human", "with a defined human disease", "defined human disease dean", "human disease dean et", "disease dean et al.", "et al. 2001 borst", "al. 2001 borst and", "2001 borst and elferink", "and elferink 2002 rees", "elferink 2002 rees et", "2002 rees et al.", "rees et al. 2009 ." ] }, { "record_id": "GLY_000594_1_307", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3858516", "r hsa", "hsa 3858516", "r hsa 3858516" ] }, { "record_id": "GLY_000594_1_307", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycogen storage", "storage disease", "disease type", "type 0", "liver gys2", "glycogen storage disease", "storage disease type", "disease type 0", "0 liver", "glycogen storage disease type", "storage disease type 0", "type 0 liver", "0 liver gys2", "glycogen storage disease type 0", "disease type 0 liver", "type 0 liver gys2", "glycogen synthase", "synthase 2", 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"fasting hypoglycemia gitzelmann et", "hypoglycemia gitzelmann et al.", "et al. 1996 orho", "al. 1996 orho et", "1996 orho et al.", "orho et al. 1998 ." ] }, { "record_id": "GLY_000594_1_308", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3878781", "r hsa", "hsa 3878781", "r hsa 3878781" ] }, { "record_id": "GLY_000594_1_308", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycogen storage", "storage disease", "disease type", "type iv", "glycogen storage disease", "storage disease type", "disease type iv", "iv gbe1", "glycogen storage disease type", "storage disease type iv", "type iv gbe1", "glycogen storage disease type iv", "disease type iv gbe1", "cytosolic glycogen", "glycogen branching", "branching enzyme", "associated with", "with glycogen", "glycogen granules", "granules transfers", "transfers terminal", "terminal alpha", "alpha 1", "1 4", "glucose blocks", "blocks to", "to form", 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the sirp family", "sirp family members", "family members sirpb", "members sirpb and", "sirpb and sirpg", "and sirpg show", "sirpg show high", "show high sequence", "high sequence similarity", "sequence similarity and", "similarity and similar", "and similar extracellular", "similar extracellular structural", "extracellular structural topology", "topology including", "including three ig", "three ig domains", "domains but", "but their ligand", "their ligand binding", "ligand binding topology", "binding topology might", "topology might differ.", "might differ. sirpb", "differ. sirpb is", "sirpb is expressed", "is expressed on", "expressed on myeloid", "on myeloid cells", "cells including", "monocytes granulocytes", "granulocytes and dcs.", "and dcs. it", "dcs. it has", "it has no", "has no known", "no known natural", "known natural ligand.", "natural ligand. sirpg", "ligand. sirpg can", "sirpg can bind", "can bind cd47", "bind cd47 but", "cd47 but with", "but with lower", "with lower affinity", "lower affinity than", "affinity than sirpa.", "signal regulatory protein alpha", "protein alpha sirpa", "cd172a is a", "is a transmembrane protein", "a transmembrane protein expressed", "transmembrane protein expressed mostly", "protein expressed mostly on", "expressed mostly on myeloid", "mostly on myeloid cells.", "on myeloid cells. cd47", "cells. cd47 a", "cd47 a widely", "a widely expressed transmembrane", "widely expressed transmembrane protein", "transmembrane protein is", "protein is a", "is a ligand for", "a ligand for sirp", "ligand for sirp alpha", "sirp alpha with", "alpha with the", "with the two proteins", "the two proteins constituting", "two proteins constituting a", "proteins constituting a cell", "constituting a cell cell", "a cell cell communication", "cell cell communication system.", "cell communication system. the", "communication system. the interaction", "system. the interaction of", "the interaction of sirpa", "interaction of sirpa with", "of sirpa with cd47", "sirpa with cd47 is", "with cd47 is important", "cd47 is important for", "is important for the", "important for the regulation", "for the regulation of", "the regulation of migration", "regulation of migration and", "of migration and phagocytosis.", "migration and phagocytosis. sirpa", "and phagocytosis. sirpa functions", "phagocytosis. sirpa functions as", "sirpa functions as a", "functions as a docking", "as a docking protein", "a docking protein to", "docking protein to recruit", "protein to recruit and", "to recruit and activate", "recruit and activate ptpn6", "activate ptpn6 shp", "ptpn6 shp 1", "shp 1 or", "1 or ptpn11", "or ptpn11 shp", "ptpn11 shp 2", "shp 2 at", "2 at the", "at the cell membrane", "the cell membrane in", "cell membrane in response", "membrane in response to", "in response to extracellular", "response to extracellular stimuli.", "to extracellular stimuli. sirpa", "extracellular stimuli. sirpa also", "stimuli. sirpa also binds", "sirpa also binds other", "also binds other intracellular", "binds other intracellular proteins", "other intracellular proteins including", "intracellular proteins including the", "proteins including the adaptor", "including the adaptor molecules", "the adaptor molecules src", "adaptor molecules src kinase", "molecules src kinase associated", "src kinase associated protein", "associated protein skap2", "protein skap2 skap55hom/r", "skap55hom/r fyn", "fyn binding protein/slp 76", "binding protein/slp 76 associated", "protein/slp 76 associated phosphoprotein", "associated phosphoprotein fyb/slap", "phosphoprotein fyb/slap 130", "fyb/slap 130 and", "130 and the", "and the tyrosine kinase", "the tyrosine kinase pyk2.", "tyrosine kinase pyk2. sirpa", "kinase pyk2. sirpa also", "pyk2. sirpa also binds", "sirpa also binds the", "also binds the extracellular", "binds the extracellular proteins", "extracellular proteins surfactant", "proteins surfactant a", "surfactant a sp", "a sp a", "sp a and", "a and surfactant", "surfactant d sp", "d sp d", "sp d .
the", "d .
the sirp", ".
the sirp family", "
the sirp family members", "sirp family members sirpb", "family members sirpb and", "members sirpb and sirpg", "sirpb and sirpg show", "and sirpg show high", "sirpg show high sequence", "show high sequence similarity", "high sequence similarity and", "sequence similarity and similar", "similarity and similar extracellular", "and similar extracellular structural", "similar extracellular structural topology", "structural topology including", "topology including three", "including three ig domains", "ig domains but", "domains but their", "but their ligand binding", "their ligand binding topology", "ligand binding topology might", "binding topology might differ.", "topology might differ. sirpb", "might differ. sirpb is", "differ. sirpb is expressed", "sirpb is expressed on", "is expressed on myeloid", "expressed on myeloid cells", "myeloid cells including", "cells including monocytes", "including monocytes granulocytes", "monocytes granulocytes and", "granulocytes and dcs. it", "and dcs. it has", "dcs. it has no", "it has no known", "has no known natural", "no known natural ligand.", "known natural ligand. sirpg", "natural ligand. sirpg can", "ligand. sirpg can bind", "sirpg can bind cd47", "can bind cd47 but", "bind cd47 but with", "cd47 but with lower", "but with lower affinity", "with lower affinity than", "lower affinity than sirpa.", "regulatory protein alpha sirpa", "alpha sirpa shps1", "sirpa shps1 cd172a", "shps1 cd172a is", "cd172a is a transmembrane", "is a transmembrane protein expressed", "a transmembrane protein expressed mostly", "transmembrane protein expressed mostly on", "protein expressed mostly on myeloid", "expressed mostly on myeloid cells.", "mostly on myeloid cells. cd47", "myeloid cells. cd47 a", "cells. cd47 a widely", "cd47 a widely expressed", "a widely expressed transmembrane protein", "expressed transmembrane protein is", "transmembrane protein is a", "protein is a ligand", "is a ligand for sirp", "a ligand for sirp alpha", "for sirp alpha with", "sirp alpha with the", "alpha with the two", "with the two proteins constituting", "the two proteins constituting a", "two proteins constituting a cell", "proteins constituting a cell cell", "constituting a cell cell communication", "a cell cell communication system.", "cell cell communication system. the", "cell communication system. the interaction", "communication system. the interaction of", "system. the interaction of sirpa", "the interaction of sirpa with", "interaction of sirpa with cd47", "of sirpa with cd47 is", "sirpa with cd47 is important", "with cd47 is important for", "cd47 is important for the", "is important for the regulation", "important for the regulation of", "for the regulation of migration", "the regulation of migration and", "regulation of migration and phagocytosis.", "of migration and phagocytosis. sirpa", "migration and phagocytosis. sirpa functions", "and phagocytosis. sirpa functions as", "phagocytosis. sirpa functions as a", "sirpa functions as a docking", "functions as a docking protein", "as a docking protein to", "a docking protein to recruit", "docking protein to recruit and", "protein to recruit and activate", "to recruit and activate ptpn6", "and activate ptpn6 shp", "activate ptpn6 shp 1", "shp 1 or ptpn11", "or ptpn11 shp 2", "shp 2 at the", "2 at the cell", "at the cell membrane in", "the cell membrane in response", "cell membrane in response to", "membrane in response to extracellular", "in response to extracellular stimuli.", "response to extracellular stimuli. sirpa", "to extracellular stimuli. sirpa also", "extracellular stimuli. sirpa also binds", "stimuli. sirpa also binds other", "sirpa also binds other intracellular", "also binds other intracellular proteins", "binds other intracellular proteins including", "other intracellular proteins including the", "intracellular proteins including the adaptor", "proteins including the adaptor molecules", "including the adaptor molecules src", "the adaptor molecules src kinase", "adaptor molecules src kinase associated", "molecules src kinase associated protein", "kinase associated protein skap2", "associated protein skap2 skap55hom/r", "skap2 skap55hom/r fyn", "skap55hom/r fyn binding", "fyn binding protein/slp 76 associated", "binding protein/slp 76 associated phosphoprotein", "76 associated phosphoprotein fyb/slap", "associated phosphoprotein fyb/slap 130", "fyb/slap 130 and the", "130 and the tyrosine", "and the tyrosine kinase pyk2.", "the tyrosine kinase pyk2. sirpa", "tyrosine kinase pyk2. sirpa also", "kinase pyk2. sirpa also binds", "pyk2. sirpa also binds the", "sirpa also binds the extracellular", "also binds the extracellular proteins", "the extracellular proteins surfactant", "extracellular proteins surfactant a", "surfactant a sp a", "sp a and surfactant", "a and surfactant d", "and surfactant d sp", "surfactant d sp d", "d sp d .", "sp d .
the sirp", "d .
the sirp family", ".
the sirp family members", "
the sirp family members sirpb", "sirp family members sirpb and", "family members sirpb and sirpg", "members sirpb and sirpg show", "sirpb and sirpg show high", "and sirpg show high sequence", "sirpg show high sequence similarity", "show high sequence similarity and", "high sequence similarity and similar", "sequence similarity and similar extracellular", "similarity and similar extracellular structural", "and similar extracellular structural topology", "extracellular structural topology including", "structural topology including three", "topology including three ig", "three ig domains but", "ig domains but their", "domains but their ligand", "but their ligand binding topology", "their ligand binding topology might", "ligand binding topology might differ.", "binding topology might differ. sirpb", "topology might differ. sirpb is", "might differ. sirpb is expressed", "differ. sirpb is expressed on", "sirpb is expressed on myeloid", "is expressed on myeloid cells", "on myeloid cells including", "myeloid cells including monocytes", "including monocytes granulocytes and", "monocytes granulocytes and dcs.", "granulocytes and dcs. it has", "and dcs. it has no", "dcs. it has no known", "it has no known natural", "has no known natural ligand.", "no known natural ligand. sirpg", "known natural ligand. sirpg can", "natural ligand. sirpg can bind", "ligand. sirpg can bind cd47", "sirpg can bind cd47 but", "can bind cd47 but with", "bind cd47 but with lower", "cd47 but with lower affinity", "but with lower affinity than", "with lower affinity than sirpa." ] }, { "record_id": "GLY_000594_1_324", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "392170", "r hsa", "hsa 392170", "r hsa 392170" ] }, { "record_id": "GLY_000594_1_324", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "adp signalling", "signalling through", "through p2y", "p2y purinoceptor", "purinoceptor 12", "adp signalling through", "signalling through p2y", "through p2y purinoceptor", "p2y purinoceptor 12", "adp signalling through p2y", "signalling through p2y purinoceptor", "through p2y purinoceptor 12", "adp signalling through p2y purinoceptor", "signalling through p2y purinoceptor 12", "co activation", "activation of", "of p2y1", "p2y1 and", "and p2y12", "p2y12 is", "is necessary", "necessary for", "for complete", "complete platelet", "platelet activation.", "activation. p2y1", "p2y1 is", "is coupled", "coupled to", "to gq", "gq and", "and helps", "helps trigger", "trigger the", "the release", "release of", "of calcium", "calcium from", "from internal", "internal stores", "leading to", "to weak", "weak and", "and reversible", "reversible platelet", "platelet aggregation.", "aggregation. p2y12", "is gi", "gi coupled", "inhibiting adenylate", "adenylate cyclase", "to decreased", "decreased camp", "a consequent", "consequent decrease", "decrease in", "in camp", "camp dependent", "dependent protein", "protein kinase", "kinase activity", "activity which", "which increases", "increases cytoplasmic", "for activation", "woulfe et", "et al.", "al. 2001", "2001 .
", ".
in", "in activated", "activated platelets", "p2y12 signaling", "signaling is", "is required", "required for", "for the", "the amplification", "amplification of", "of aggregation", "aggregation induced", "induced by", "by all", "all platelet", "platelet agonists", "agonists including", "including collagen", "adrenaline and", "and serotonin.", "serotonin. p2y12", "p2y12 activation", "activation causes", "causes potentiation", "potentiation of", "of thromboxane", "thromboxane generation", "secretion leading", "to irreversible", "irreversible platelet", "platelet aggregation", "aggregation and", "and thrombus", "thrombus stabilization.", "co activation of", "activation of p2y1", "of p2y1 and", "p2y1 and p2y12", "and p2y12 is", "p2y12 is necessary", "is necessary for", "necessary for complete", "for complete platelet", "complete platelet activation.", "platelet activation. p2y1", "activation. p2y1 is", "p2y1 is coupled", "is coupled to", "coupled to gq", "to gq and", "gq and helps", "and helps trigger", "helps trigger the", "trigger the release", "the release of", "release of calcium", "of calcium from", "calcium from internal", "from internal stores", "stores leading", "leading to weak", "to weak and", "weak and reversible", "and reversible platelet", "reversible platelet aggregation.", "platelet aggregation. p2y12", "aggregation. p2y12 is", "p2y12 is gi", "is gi coupled", "coupled inhibiting", "inhibiting adenylate cyclase", "cyclase leading", "leading to decreased", "to decreased camp", "camp a", "a consequent decrease", "consequent decrease in", "decrease in camp", "in camp dependent", "camp dependent protein", "dependent protein kinase", "protein kinase activity", "kinase activity which", "activity which increases", "which increases cytoplasmic", "cytoplasmic ca2+", "necessary for activation", "activation woulfe", "woulfe et al.", "et al. 2001", "al. 2001 .
", "2001 .
in", ".
in activated", "in activated platelets", "platelets p2y12", "p2y12 signaling is", "signaling is required", "is required for", "required for the", "for the amplification", "the amplification of", "amplification of aggregation", "of aggregation induced", "aggregation induced by", "induced by all", "by all platelet", "all platelet agonists", "platelet agonists including", "agonists including collagen", "collagen thrombin", "thrombin thromboxane", "thromboxane adrenaline", "adrenaline and serotonin.", "and serotonin. p2y12", "serotonin. p2y12 activation", "p2y12 activation causes", "activation causes potentiation", "causes potentiation of", "potentiation of thromboxane", "of thromboxane generation", "generation secretion", "secretion leading to", "leading to irreversible", "to irreversible platelet", "irreversible platelet aggregation", "platelet aggregation and", "aggregation and thrombus", "and thrombus stabilization.", "co activation of p2y1", "activation of p2y1 and", "of p2y1 and p2y12", "p2y1 and p2y12 is", "and p2y12 is necessary", "p2y12 is necessary for", "is necessary for complete", "necessary for complete platelet", "for complete platelet activation.", "complete platelet activation. p2y1", "platelet activation. p2y1 is", "activation. p2y1 is coupled", "p2y1 is coupled to", "is coupled to gq", "coupled to gq and", "to gq and helps", "gq and helps trigger", "and helps trigger the", "helps trigger the release", "trigger the release of", "the release of calcium", "release of calcium from", "of calcium from internal", "calcium from internal stores", "internal stores leading", "stores leading to", "leading to weak and", "to weak and reversible", "weak and reversible platelet", "and reversible platelet aggregation.", "reversible platelet aggregation. p2y12", "platelet aggregation. p2y12 is", "aggregation. p2y12 is gi", "p2y12 is gi coupled", "gi coupled inhibiting", "coupled inhibiting adenylate", "adenylate cyclase leading", "cyclase leading to", "leading to decreased camp", "decreased camp a", "camp a consequent", "a consequent decrease in", "consequent decrease in camp", "decrease in camp dependent", "in camp dependent protein", "camp dependent protein kinase", "dependent protein kinase activity", "protein kinase activity which", "kinase activity which increases", "activity which increases cytoplasmic", "increases cytoplasmic ca2+", "ca2+ necessary", "for activation woulfe", "activation woulfe et", "woulfe et al. 2001", "et al. 2001 .
", "al. 2001 .
in", "2001 .
in activated", ".
in activated platelets", "activated platelets p2y12", "platelets p2y12 signaling", "p2y12 signaling is required", "signaling is required for", "is required for the", "required for the amplification", "for the amplification of", "the amplification of aggregation", "amplification of aggregation induced", "of aggregation induced by", "aggregation induced by all", "induced by all platelet", "by all platelet agonists", "all platelet agonists including", "platelet agonists including collagen", "including collagen thrombin", "thromboxane adrenaline and", "adrenaline and serotonin. p2y12", "and serotonin. p2y12 activation", "serotonin. p2y12 activation causes", "p2y12 activation causes potentiation", "activation causes potentiation of", "causes potentiation of thromboxane", "potentiation of thromboxane generation", "thromboxane generation secretion", "generation secretion leading", "secretion leading to irreversible", "leading to irreversible platelet", "to irreversible platelet aggregation", "irreversible platelet aggregation and", "platelet aggregation and thrombus", "aggregation and thrombus stabilization.", "co activation of p2y1 and", "activation of p2y1 and p2y12", "of p2y1 and p2y12 is", "p2y1 and p2y12 is necessary", "and p2y12 is necessary for", "p2y12 is necessary for complete", "is necessary for complete platelet", "necessary for complete platelet activation.", "for complete platelet activation. p2y1", "complete platelet activation. p2y1 is", "platelet activation. p2y1 is coupled", "activation. p2y1 is coupled to", "p2y1 is coupled to gq", "is coupled to gq and", "coupled to gq and helps", "to gq and helps trigger", "gq and helps trigger the", "and helps trigger the release", "helps trigger the release of", "trigger the release of calcium", "the release of calcium from", "release of calcium from internal", "of calcium from internal stores", "from internal stores leading", "internal stores leading to", "stores leading to weak", "leading to weak and reversible", "to weak and reversible platelet", "weak and reversible platelet aggregation.", "and reversible platelet aggregation. p2y12", "reversible platelet aggregation. p2y12 is", "platelet aggregation. p2y12 is gi", "aggregation. p2y12 is gi coupled", "is gi coupled inhibiting", "gi coupled inhibiting adenylate", "coupled inhibiting adenylate cyclase", "inhibiting adenylate cyclase leading", "adenylate cyclase leading to", "cyclase leading to decreased", "to decreased camp a", "decreased camp a consequent", "camp a consequent decrease", "a consequent decrease in camp", "consequent decrease in camp dependent", "decrease in camp dependent protein", "in camp dependent protein kinase", "camp dependent protein kinase activity", "dependent protein kinase activity which", "protein kinase activity which increases", "kinase activity which increases cytoplasmic", "which increases cytoplasmic ca2+", "ca2+ necessary for", "necessary for activation woulfe", "for activation woulfe et", "activation woulfe et al.", "woulfe et al. 2001 .
", "et al. 2001 .
in", "al. 2001 .
in activated", "2001 .
in activated platelets", "in activated platelets p2y12", "activated platelets p2y12 signaling", "platelets p2y12 signaling is", "p2y12 signaling is required for", "signaling is required for the", "is required for the amplification", "required for the amplification of", "for the amplification of aggregation", "the amplification of aggregation induced", "amplification of aggregation induced by", "of aggregation induced by all", "aggregation induced by all platelet", "induced by all platelet agonists", "by all platelet agonists including", "all platelet agonists including collagen", "agonists including collagen thrombin", "collagen thrombin thromboxane", "thrombin thromboxane adrenaline", "thromboxane adrenaline and serotonin.", "adrenaline and serotonin. p2y12 activation", "and serotonin. p2y12 activation causes", "serotonin. p2y12 activation causes potentiation", "p2y12 activation causes potentiation of", "activation causes potentiation of thromboxane", "causes potentiation of thromboxane generation", "of thromboxane generation secretion", "thromboxane generation secretion leading", "generation secretion leading to", "secretion leading to irreversible platelet", "leading to irreversible platelet aggregation", "to irreversible platelet aggregation and", "irreversible platelet aggregation and thrombus", "platelet aggregation and thrombus stabilization." ] }, { "record_id": "GLY_000594_1_325", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "392451", "r hsa", "hsa 392451", "r hsa 392451" ] }, { "record_id": "GLY_000594_1_325", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "g beta:gamma", "beta:gamma signalling", "signalling through", "through pi3kgamma", "g beta:gamma signalling", "beta:gamma signalling through", "signalling through pi3kgamma", "g beta:gamma signalling through", "beta:gamma signalling through pi3kgamma", "g beta:gamma signalling through pi3kgamma", "pi3k gamma", "is a", "a heterodimer", "heterodimer consisting", "consisting of", "of a", "a p110", "p110 catalytic", "catalytic subunit", "subunit associated", "associated with", "with a", "a regulatory", "regulatory p101", "p101 or", "or p84", "p84 subunit.", "subunit. pi3kg", "pi3kg is", "is most", "most highly", "highly expressed", "expressed in", "in neutrophils", "where the", "the p101", "p101 form", "form predominates", "approximately 95%", "95% .", ". g", "beta:gamma recruits", "recruits pi3kg", "pi3kg to", "to the", "the plasma", "plasma membrane", "both activating", "activating pi3kg", "pi3kg and", "and providing", "providing access", "access to", "to its", "its substrate", "substrate pip2", "which is", "is converted", "converted to", "to pip3.", "gamma pi3kg", "is a heterodimer", "a heterodimer consisting", "heterodimer consisting of", "consisting of a", "of a p110", "a p110 catalytic", "p110 catalytic subunit", "catalytic subunit associated", "subunit associated with", "associated with a", "with a regulatory", "a regulatory p101", "regulatory p101 or", "p101 or p84", "or p84 subunit.", "p84 subunit. pi3kg", "subunit. pi3kg is", "pi3kg is most", "is most highly", "most highly expressed", "highly expressed in", "expressed in neutrophils", "neutrophils where", "where the p101", "the p101 form", "p101 form predominates", "predominates approximately", "approximately 95% .", "95% . g", ". g beta:gamma", "g beta:gamma recruits", "beta:gamma recruits pi3kg", "recruits pi3kg to", "pi3kg to the", "to the plasma", "the plasma membrane", "membrane both", "both activating pi3kg", "activating pi3kg and", "pi3kg and providing", "and providing access", "providing access to", "access to its", "to its substrate", "its substrate pip2", "pip2 which", "which is converted", "is converted to", "converted to pip3.", "pi3k gamma pi3kg", "pi3kg is a", "is a heterodimer consisting", "a heterodimer consisting of", "heterodimer consisting of a", "consisting of a p110", "of a p110 catalytic", "a p110 catalytic subunit", "p110 catalytic subunit associated", "catalytic subunit associated with", "subunit associated with a", "associated with a regulatory", "with a regulatory p101", "a regulatory p101 or", "regulatory p101 or p84", "p101 or p84 subunit.", "or p84 subunit. pi3kg", "p84 subunit. pi3kg is", "subunit. pi3kg is most", "pi3kg is most highly", "is most highly expressed", "most highly expressed in", "highly expressed in neutrophils", "in neutrophils where", "neutrophils where the", "where the p101 form", "the p101 form predominates", "form predominates approximately", "predominates approximately 95%", "approximately 95% . g", "95% . g beta:gamma", ". g beta:gamma recruits", "g beta:gamma recruits pi3kg", "beta:gamma recruits pi3kg to", "recruits pi3kg to the", "pi3kg to the plasma", "to the plasma membrane", "plasma membrane both", "membrane both activating", "both activating pi3kg and", "activating pi3kg and providing", "pi3kg and providing access", "and providing access to", "providing access to its", "access to its substrate", "to its substrate pip2", "substrate pip2 which", "pip2 which is", "which is converted to", "is converted to pip3.", "gamma pi3kg is", "pi3kg is a heterodimer", "is a heterodimer consisting of", "a heterodimer consisting of a", "heterodimer consisting of a p110", "consisting of a p110 catalytic", "of a p110 catalytic subunit", "a p110 catalytic subunit associated", "p110 catalytic subunit associated with", "catalytic subunit associated with a", "subunit associated with a regulatory", "associated with a regulatory p101", "with a regulatory p101 or", "a regulatory p101 or p84", "regulatory p101 or p84 subunit.", "p101 or p84 subunit. pi3kg", "or p84 subunit. pi3kg is", "p84 subunit. pi3kg is most", "subunit. pi3kg is most highly", "pi3kg is most highly expressed", "is most highly expressed in", "most highly expressed in neutrophils", "expressed in neutrophils where", "in neutrophils where the", "neutrophils where the p101", "where the p101 form predominates", "p101 form predominates approximately", "form predominates approximately 95%", "predominates approximately 95% .", "approximately 95% . g beta:gamma", "95% . g beta:gamma recruits", ". g beta:gamma recruits pi3kg", "g beta:gamma recruits pi3kg to", "beta:gamma recruits pi3kg to the", "recruits pi3kg to the plasma", "pi3kg to the plasma membrane", "the plasma membrane both", "plasma membrane both activating", "membrane both activating pi3kg", "both activating pi3kg and providing", "activating pi3kg and providing access", "pi3kg and providing access to", "and providing access to its", "providing access to its substrate", "access to its substrate pip2", "its substrate pip2 which", "substrate pip2 which is", "pip2 which is converted", "which is converted to pip3." ] }, { "record_id": "GLY_000594_1_326", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "392851", "r hsa", "hsa 392851", "r hsa 392851" ] }, { "record_id": "GLY_000594_1_326", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "prostacyclin signalling", "signalling through", "through prostacyclin", "prostacyclin receptor", "prostacyclin signalling through", "signalling through prostacyclin", "through prostacyclin receptor", "prostacyclin signalling through prostacyclin", "signalling through prostacyclin receptor", "prostacyclin signalling through prostacyclin receptor", "is continuously", "continuously produced", "produced by", "by healthy", "healthy vascular", "vascular endothelial", "endothelial cells.", "cells. it", "it inhibits", "inhibits platelet", "platelet activation", "activation through", "through interaction", "interaction with", "with the", "the gs", "gs coupled", "coupled receptor", "receptor ptgir", "leading to", "to increased", "increased camp", "a consequent", "consequent increase", "increase in", "in camp", "camp dependent", "dependent protein", "protein kinase", "kinase activity", "activity which", "which prevents", "prevents increases", "increases of", "of cytoplasmic", "necessary for", "for activation", "woulfe et", "et al.", "al. 2001", "2001 .", ". pgi2", "pgi2 is", "is also", "also an", "an effective", "effective vasodilator.", "vasodilator. these", "these effects", "effects oppose", "oppose the", "the effects", "effects of", "of thromboxane", "another eicosanoid", "creating a", "a balance", "balance of", "of blood", "blood circulation", "circulation and", "and platelet", "platelet activation.", "prostacyclin pgi2", "is continuously produced", "continuously produced by", "produced by healthy", "by healthy vascular", "healthy vascular endothelial", "vascular endothelial cells.", "endothelial cells. it", "cells. it inhibits", "it inhibits platelet", "inhibits platelet activation", "platelet activation through", "activation through interaction", "through interaction with", "interaction with the", "with the gs", "the gs coupled", "gs 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pasquale", "superior colliculus pasquale 2005", "colliculus pasquale 2005 ." ] }, { "record_id": "GLY_000594_1_329", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3928664", "r hsa", "hsa 3928664", "r hsa 3928664" ] }, { "record_id": "GLY_000594_1_329", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ephrin signaling", "the interaction", "interaction between", "between ephrin", "ligands and", "and eph", "eph receptors", "receptors results", "results not", "not only", "only in", "in forward", "forward signaling", "signaling through", "through the", "the eph", "eph receptor", "but also", "also in", "in 'reverse'", "'reverse' signaling", "the efn", "efn ligand", "ligand itself.", "itself. reverse", "reverse signaling", "through efnb", "efnb is", "is required", "required for", "for correct", "correct spine", "spine morphogenesis", "morphogenesis and", "and proper", "proper path", "path finding", 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internalization", "internalization by", "by endocytosis", "marston et", "al. 2003", "2003 .", "despite high affinity", "high affinity multimeric", "affinity multimeric interaction", "multimeric interaction between", "interaction between ephs", "between ephs and", "ephs and ephrins", "ephrins efns", "the cellular response", "cellular response to", "response to eph", "to eph efn", "eph efn engagement", "efn engagement is", "engagement is usually", "is usually repulsion", "usually repulsion between", "repulsion between the", "between the two", "the two cells", "two cells and", "cells and signal", "and signal termination.", "signal termination. these", "termination. these repulsive", "these repulsive responses", "repulsive responses induce", "responses induce an", "induce an eph", "an eph receptor", "eph receptor expressing", "receptor expressing cell", "expressing cell to", "cell to retract", "to retract from", "retract from an", "from an ephrin", "an ephrin expressing", "ephrin expressing cell", "expressing cell after", "cell after establishing", "after establishing initial", "establishing initial contact.", "initial contact. the", "contact. the repulsive", "the repulsive responses", "repulsive responses mediated", "responses mediated by", "mediated by eph", "by eph receptors", "eph receptors in", "receptors in the", "in the growth", "the growth cone", "growth cone at", "cone at the", "at the leading", "the leading edge", "leading edge of", "edge of extending", "of extending axons", "extending axons and", "axons and in", "and in axonal", "in axonal collateral", "axonal collateral branches", "collateral branches contribute", "branches contribute to", "contribute to the", "to the formation", "the formation of", "formation of selective", "of selective neuronal", "selective neuronal connections.", "neuronal connections. it", "connections. it is", "it is unclear", "is unclear how", "unclear how high", "how high affinity", "high affinity trans", "affinity trans 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"cell cell contact", "contact while", "while the second", "the second one", "second one is", "one is rapid", "is rapid endocytosis", "rapid endocytosis of", "endocytosis of whole", "of whole eph:efn", "whole eph:efn complexes", "eph:efn complexes during", "complexes during the", "during the retraction", "the retraction of", "retraction of the", "of the interacting", "the interacting cells", "interacting cells or", "cells or neuronal", "or neuronal growth", "neuronal growth cones", "cones egea", "egea & klein", "& klein 2007", "2007 janes", "janes et al.", "et al. 2005", "al. 2005 .", "2005 . rac", ". rac also", "rac also plays", "also plays an", "plays an essential", "an essential role", "essential role during", "role during growth", "during growth cone", "growth cone collapse", "cone collapse by", "collapse by promoting", "by promoting actin", "promoting actin polymerization", "actin polymerization that", "polymerization that drives", "that drives membrane", "drives membrane internalization", "membrane internalization by", "internalization by endocytosis", "endocytosis marston", "marston et al.", "et al. 2003", "al. 2003 .", "despite high affinity multimeric", "high affinity multimeric interaction", "affinity multimeric interaction between", "multimeric interaction between ephs", "interaction between ephs and", "between ephs and ephrins", "and ephrins efns", "efns the", "the cellular response to", "cellular response to eph", "response to eph efn", "to eph efn engagement", "eph efn engagement is", "efn engagement is usually", "engagement is usually repulsion", "is usually repulsion between", "usually repulsion between the", "repulsion between the two", "between the two cells", "the two cells and", "two cells and signal", "cells and signal termination.", "and signal termination. these", "signal termination. these repulsive", "termination. these repulsive responses", "these repulsive responses induce", "repulsive responses induce an", "responses induce an 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"promoting actin polymerization that", "actin polymerization that drives", "polymerization that drives membrane", "that drives membrane internalization", "drives membrane internalization by", "membrane internalization by endocytosis", "by endocytosis marston", "endocytosis marston et", "marston et al. 2003", "et al. 2003 .", "despite high affinity multimeric interaction", "high affinity multimeric interaction between", "affinity multimeric interaction between ephs", "multimeric interaction between ephs and", "interaction between ephs and ephrins", "ephs and ephrins efns", "efns the cellular", "the cellular response to eph", "cellular response to eph efn", "response to eph efn engagement", "to eph efn engagement is", "eph efn engagement is usually", "efn engagement is usually repulsion", "engagement is usually repulsion between", "is usually repulsion between the", "usually repulsion between the two", "repulsion between the two cells", "between the two cells and", "the two cells and signal", "two cells and signal termination.", "cells and signal termination. these", "and signal termination. these repulsive", "signal termination. these repulsive responses", "termination. these repulsive responses induce", "these repulsive responses induce an", "repulsive responses induce an eph", "responses induce an eph receptor", "induce an eph receptor expressing", "an eph receptor expressing cell", "eph receptor expressing cell to", "receptor expressing cell to retract", "expressing cell to retract from", "cell to retract from an", "to retract from an ephrin", "retract from an ephrin expressing", "from an ephrin expressing cell", "an ephrin expressing cell after", "ephrin expressing cell after establishing", "expressing cell after establishing initial", "cell after establishing initial contact.", "after establishing initial contact. the", "establishing initial contact. the repulsive", "initial contact. the repulsive responses", "contact. the repulsive responses mediated", "the 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kinases. phosphorylation of", "fes kinases. phosphorylation of crmps", "kinases. phosphorylation of crmps by", "phosphorylation of crmps by these", "of crmps by these kinases", "crmps by these kinases blocks", "by these kinases blocks the", "these kinases blocks the ability", "kinases blocks the ability of", "blocks the ability of crmp", "the ability of crmp to", "ability of crmp to bind", "of crmp to bind to", "crmp to bind to tubulin", "to bind to tubulin dimers", "to tubulin dimers subsequently", "tubulin dimers subsequently induces", "dimers subsequently induces depolymerization", "subsequently induces depolymerization of f", "induces depolymerization of f actin", "of f actin and", "f actin and ultimately", "actin and ultimately leads", "and ultimately leads to growth", "ultimately leads to growth cone", "leads to growth cone collapse." ] }, { "record_id": "GLY_000594_1_334", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "400042", "r hsa", "hsa 400042", "r hsa 400042" ] }, { "record_id": "GLY_000594_1_334", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "adrenaline noradrenaline", "noradrenaline inhibits", "inhibits insulin", "insulin secretion", "adrenaline noradrenaline inhibits", "noradrenaline inhibits insulin", "inhibits insulin secretion", "adrenaline noradrenaline inhibits insulin", "noradrenaline inhibits insulin secretion", "adrenaline noradrenaline inhibits insulin secretion", "the catecholamines", "catecholamines adrenaline", "and noradrenaline", "inhibit insulin", "secretion from", "from pancreatic", "pancreatic beta", "beta cells.", "cells. four", "four effects", "effects are", "are seen", "seen in", "in the", "the cells:
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3.", "of the cell.
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4.", "of calcium influx.
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4. inhibition of", "influx.
4. inhibition of adenylyl", "inhibition of adenylyl cyclase", "of adenylyl cyclase activity.
the", "adenylyl cyclase activity.
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after activation by", "unknown.
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1.", "seen in the cells:
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2.", "the major effect.
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3.", "repolarization of the cell.
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3. closing of", "the cell.
3. closing of l", "cell.
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4.", "inhibition of calcium influx.
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4. inhibition of", "calcium influx.
4. inhibition of adenylyl", "influx.
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the", "of adenylyl cyclase activity.
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the first event in adrenaline/noradrenaline", "first event in adrenaline/noradrenaline signaling", "event in adrenaline/noradrenaline signaling in", "in adrenaline/noradrenaline signaling in beta", "adrenaline/noradrenaline signaling in beta cells", "signaling in beta cells is", "in beta cells is the", "beta cells is the binding", "cells is the binding of", "is the binding of adrenaline", "the binding of adrenaline or", "binding of adrenaline or noradrenaline", "of adrenaline or noradrenaline to", "adrenaline or noradrenaline to alpha", "or noradrenaline to alpha 2", "noradrenaline to alpha 2 adrenergic", "to alpha 2 adrenergic receptors", "2 adrenergic receptors which", "adrenergic receptors which are", "receptors which are g", "which are g protein coupled", "are g protein coupled receptors.", "g protein coupled receptors. binding", "protein coupled receptors. binding activates", "coupled receptors. binding activates the", "receptors. binding activates the alpha", "binding activates the alpha subunits", "activates the alpha subunits in", "the alpha subunits in heterotrimeric", "alpha subunits in heterotrimeric gi", "subunits in heterotrimeric gi and", "in heterotrimeric gi and go", "heterotrimeric gi and go complexes", "gi and go complexes to", "and go complexes to exchange", "go complexes to exchange gdp", "complexes to exchange gdp for", "to exchange gdp for gtp", "gdp for gtp forming", "for gtp forming the", "gtp forming the active", "forming the active g alpha:gtp", "the active g alpha:gtp complex.", "active g alpha:gtp complex. experiments", "g alpha:gtp complex. experiments using", "alpha:gtp complex. experiments using specific", "complex. experiments using specific antibodies", "experiments using specific antibodies against", "using specific antibodies against the", "specific antibodies against the alpha", "antibodies against the alpha subunits", "against the alpha subunits in", "the alpha subunits in mice", "alpha subunits in mice show", "subunits in mice show that", "in mice show that gi", "mice show that gi alpha", "show that gi alpha 1", "gi alpha 1 gi", "alpha 1 gi alpha", "1 gi alpha 2", "gi alpha 2 and", "alpha 2 and go", "2 and go alpha", "and go alpha 2 are", "go alpha 2 are responsible", "alpha 2 are responsible for", "2 are responsible for adrenergic", "are responsible for adrenergic effects.", "responsible for adrenergic effects. the", "for adrenergic effects. the exact", "adrenergic effects. the exact beta", "effects. the exact beta and", "the exact beta and gamma", "exact beta and gamma subunits", "beta and gamma subunits of", "and gamma subunits of the", "gamma subunits of the heterotrimeric", "subunits of the heterotrimeric g", "of the heterotrimeric g proteins", "the heterotrimeric g proteins are", "heterotrimeric g proteins are unknown.
after", "g proteins are unknown.
after activation", "proteins are unknown.
after activation by", "are unknown.
after activation by gtp", "activation by gtp the", "by gtp the heterotrimeric", "gtp the heterotrimeric complex", "the heterotrimeric complex dissociates into", "heterotrimeric complex dissociates into the", "complex dissociates into the g", "dissociates into the g alpha:gtp", "into the g alpha:gtp complex", "the g alpha:gtp complex and", "g alpha:gtp complex and the", "alpha:gtp complex and the beta:gamma", "complex and the beta:gamma complex.", "and the beta:gamma complex. the", "the beta:gamma complex. the g", "beta:gamma complex. the g alpha:gtp", "complex. the g alpha:gtp complex", "the g alpha:gtp complex causes", "g alpha:gtp complex causes the", "alpha:gtp complex causes the inhibition", "complex causes the inhibition of", "causes the inhibition of exocytosis", "the inhibition of exocytosis by", "inhibition of exocytosis by an", "of exocytosis by an unknown", "exocytosis by an unknown mechanism", "by an unknown mechanism that", "an unknown mechanism that involves", "unknown mechanism that involves protein", "mechanism that involves protein acylation.", "that involves protein acylation. this", "involves protein acylation. this is", "protein acylation. this is responsible", "acylation. this is responsible for", "this is responsible for most", "is responsible for most of", "responsible for most of the", "for most of the observed", "most of the observed inhibition", "of the observed inhibition of", "the observed inhibition of insulin", "observed inhibition of insulin secretion.", "inhibition of insulin secretion. additionally", "insulin secretion. additionally the", "secretion. additionally the g", "additionally the g alpha:gtp", "the g alpha:gtp complex activates", "alpha:gtp complex activates opens", "activates opens katp", "katp channels allowing the", "channels allowing the cell", "allowing the cell to repolarize.", "the cell to repolarize. the", "cell to repolarize. the beta:gamma", "to repolarize. the beta:gamma complex", "repolarize. the beta:gamma complex inhibits", "beta:gamma complex inhibits closes", "inhibits closes voltage", "closes voltage dependent calcium", "dependent calcium channels reducing", "calcium channels reducing the", "channels reducing the intracellular", "reducing the intracellular calcium concentration", "intracellular calcium concentration and", "calcium concentration and inhibits", "concentration and inhibits adenylyl", "inhibits adenylyl cyclase reducing", "adenylyl cyclase reducing the", "cyclase reducing the intracellular", "reducing the intracellular camp concentration." ] }, { "record_id": "GLY_000594_1_335", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "400206", "r hsa", "hsa 400206", "r hsa 400206" ] }, { "record_id": "GLY_000594_1_335", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of lipid", "lipid metabolism", "metabolism by", "by pparalpha", "regulation of lipid", "of lipid metabolism", "lipid metabolism by", "metabolism by pparalpha", "regulation of lipid metabolism", "of lipid metabolism by", "lipid metabolism by pparalpha", "regulation of lipid metabolism by", "of lipid metabolism by pparalpha", "peroxisome proliferator", "proliferator activated", "activated receptor", "receptor alpha", "ppar alpha", "is the", "the major", "major regulator", "regulator of", "of fatty", "fatty acid", "acid oxidation", "oxidation in", "in the", "the liver.", "liver. pparalpha", "pparalpha is", "is also", "also the", "the target", "target of", "of fibrate", "fibrate drugs", "drugs used", "used to", "to treat", "treat abnormal", "abnormal plasma", "plasma lipid", "lipid levels.", "levels.
ppar", "
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the", "
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ppar", "levels.
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the", "bonds.
the ppar", "
the ppar alpha:rxr", "ppar alpha:rxr alpha", "alpha:rxr alpha heterodimer", "alpha heterodimer binds", "heterodimer binds peroxisome", "binds peroxisome proliferator", "peroxisome proliferator receptor", "proliferator receptor elements", "elements ppres", "ppres in", "in and around", "and around target", "around target genes.", "target genes. binding", "genes. binding of", "binding of fatty", "of fatty acids", "fatty acids and", "acids and synthetic", "and synthetic ligands", "synthetic ligands causes", "ligands causes a", "causes a conformational", "a conformational change", "conformational change in", "change in ppar", "in ppar alpha", "ppar alpha such", "alpha such that", "such that it", "that it releases", "it releases the", "releases the corepressors", "the corepressors and", "corepressors and binds", "and binds coactivators", "coactivators cbp", "cbp src hat", "src hat complex", "complex asc", "complex and", "and trap mediator", "trap mediator complex", "complex which", "which initiate transcription", "initiate transcription of", "transcription of the", "of the target", "the target genes.
target", "target genes.
target genes", "genes.
target genes of", "genes of ppar", "of ppar alpha", "ppar alpha participate", "alpha participate in", "participate in fatty", "in fatty acid", "fatty acid transport", "transport fatty", "oxidation triglyceride", "clearance lipoprotein", "production and", "and cholesterol homeostasis.", "peroxisome proliferator activated receptor", "proliferator activated receptor alpha", "receptor alpha ppar", "alpha ppar alpha", "alpha is the", "is the major regulator", "the major regulator of", "major regulator of fatty", "regulator of fatty acid", "of fatty acid oxidation", "fatty acid oxidation in", "acid oxidation in the", "oxidation in the liver.", "in the liver. pparalpha", "the liver. pparalpha is", "liver. pparalpha is also", "pparalpha is also the", "is also the target", "also the target of", "the target of fibrate", "target of fibrate drugs", "of fibrate drugs used", "fibrate drugs used to", "drugs used to treat", "used to treat abnormal", "to treat abnormal plasma", "treat abnormal plasma lipid", "abnormal plasma lipid levels.", "plasma lipid levels.
ppar", "lipid levels.
ppar alpha", "levels.
ppar alpha is", "
ppar alpha is a", "alpha is a type", "is a type ii", "a type ii nuclear", "type ii nuclear receptor", "nuclear receptor its", "receptor its subcellular", "its subcellular location does", "subcellular location does not", "location does not depend", "does not depend on", "not depend on ligand", "depend on ligand binding", "on ligand binding .", "ligand binding . ppar", "binding . ppar alpha", ". ppar alpha forms", "ppar alpha forms heterodimers", "alpha forms heterodimers with", "forms heterodimers with retinoid", "heterodimers with retinoid x", "with retinoid x receptor", "retinoid x receptor alpha", "receptor alpha rxr", "alpha rxr alpha", "alpha another", "another type ii nuclear", "type ii nuclear receptor.", "ii nuclear receptor. ppar", "nuclear receptor. ppar alpha", "receptor. ppar alpha is", "ppar alpha is activated", "alpha is activated by", "is activated by binding", "activated by binding fatty", "by binding fatty acid", "binding fatty acid ligands", "acid ligands especially", "ligands especially polyunsaturated", "especially polyunsaturated fatty acids", "polyunsaturated fatty acids having", "fatty acids having 18", "acids having 18 22", "having 18 22 carbon", "18 22 carbon groups", "22 carbon groups and", "carbon groups and 2", "groups and 2 6", "and 2 6 double", "2 6 double bonds.", "6 double bonds.
the", "double bonds.
the ppar", "bonds.
the ppar alpha:rxr", "
the ppar alpha:rxr alpha", "ppar alpha:rxr alpha heterodimer", "alpha:rxr alpha heterodimer binds", "alpha heterodimer binds peroxisome", "heterodimer binds peroxisome proliferator", "binds peroxisome proliferator receptor", "peroxisome proliferator receptor elements", "receptor elements ppres", "ppres in and", "in and around target", "and around target genes.", "around target genes. binding", "target genes. binding of", "genes. binding of fatty", "binding of fatty acids", "of fatty acids and", "fatty acids and synthetic", "acids and synthetic ligands", "and synthetic ligands causes", "synthetic ligands causes a", "ligands causes a conformational", "causes a conformational change", "a conformational change in", "conformational change in ppar", "change in ppar alpha", "in ppar alpha such", "ppar alpha such that", "alpha such that it", "such that it releases", "that it releases the", "it releases the corepressors", "releases the corepressors and", "the corepressors and binds", "corepressors and binds coactivators", "binds coactivators cbp", "coactivators cbp src", "cbp src hat complex", "hat complex asc", "complex asc complex", "asc complex and", "complex and trap", "and trap mediator complex", "mediator complex which", "complex which initiate", "which initiate transcription of", "initiate transcription of the", "transcription of the target", "of the target genes.
target", "the target genes.
target genes", "target genes.
target genes of", "genes.
target genes of ppar", "genes of ppar alpha", "of ppar alpha participate", "ppar alpha participate in", "alpha participate in fatty", "participate in fatty acid", "in fatty acid transport", "acid transport fatty", "transport fatty acid", "acid oxidation triglyceride", "oxidation triglyceride clearance", "triglyceride clearance lipoprotein", "clearance lipoprotein production", "lipoprotein production and", "production and cholesterol", "peroxisome proliferator activated receptor alpha", "activated receptor alpha ppar", "receptor alpha ppar alpha", "ppar alpha is the", "alpha is the major", "is the major regulator of", "the major regulator of fatty", "major regulator of fatty acid", "regulator of fatty acid oxidation", "of fatty acid oxidation in", "fatty acid oxidation in the", "acid oxidation in the liver.", "oxidation in the liver. pparalpha", "in the liver. pparalpha is", "the liver. pparalpha is also", "liver. pparalpha is also the", "pparalpha is also the target", "is also the target of", "also the target of fibrate", "the target of fibrate drugs", "target of fibrate drugs used", "of fibrate drugs used to", "fibrate drugs used to treat", "drugs used to treat abnormal", "used to treat abnormal plasma", "to treat abnormal plasma lipid", "treat abnormal plasma lipid levels.", "abnormal plasma lipid levels.
ppar", "plasma lipid levels.
ppar alpha", "lipid levels.
ppar alpha is", "levels.
ppar alpha is a", "
ppar alpha is a type", "alpha is a type ii", "is a type ii nuclear", "a type ii nuclear receptor", "ii nuclear receptor its", "nuclear receptor its subcellular", "receptor its subcellular location", "its subcellular location does not", "subcellular location does not depend", "location does not depend on", "does not depend on ligand", "not depend on ligand binding", "depend on ligand binding .", "on ligand binding . ppar", "ligand binding . ppar alpha", "binding . ppar alpha forms", ". ppar alpha forms heterodimers", "ppar alpha forms heterodimers with", "alpha forms heterodimers with retinoid", "forms heterodimers with retinoid x", "heterodimers with retinoid x receptor", "with retinoid x receptor alpha", "x receptor alpha rxr", "receptor alpha rxr alpha", "rxr alpha another", "alpha another type", "another type ii nuclear receptor.", "type ii nuclear receptor. ppar", "ii nuclear receptor. ppar alpha", "nuclear receptor. ppar alpha is", "receptor. ppar alpha is activated", "ppar alpha is activated by", "alpha is activated by binding", "is activated by binding fatty", "activated by binding fatty acid", "by binding fatty acid ligands", "fatty acid ligands especially", "acid ligands especially polyunsaturated", "ligands especially polyunsaturated fatty", "especially polyunsaturated fatty acids having", "polyunsaturated fatty acids having 18", "fatty acids having 18 22", "acids having 18 22 carbon", "having 18 22 carbon groups", "18 22 carbon groups and", "22 carbon groups and 2", "carbon groups and 2 6", "groups and 2 6 double", "and 2 6 double bonds.", "2 6 double bonds.
the", "6 double bonds.
the ppar", "double bonds.
the ppar alpha:rxr", "bonds.
the ppar alpha:rxr alpha", "
the ppar alpha:rxr alpha heterodimer", "ppar alpha:rxr alpha heterodimer binds", "alpha:rxr alpha heterodimer binds peroxisome", "alpha heterodimer binds peroxisome proliferator", "heterodimer binds peroxisome proliferator receptor", "binds peroxisome proliferator receptor elements", "proliferator receptor elements ppres", "elements ppres in", "ppres in and around", "in and around target genes.", "and around target genes. binding", "around target genes. binding of", "target genes. binding of fatty", "genes. binding of fatty acids", "binding of fatty acids and", "of fatty acids and synthetic", "fatty acids and synthetic ligands", "acids and synthetic ligands causes", "and synthetic ligands causes a", "synthetic ligands causes a conformational", "ligands causes a conformational change", "causes a conformational change in", "a conformational change in ppar", "conformational change in ppar alpha", "change in ppar alpha such", "in ppar alpha such that", "ppar alpha such that it", "alpha such that it releases", "such that it releases the", "that it releases the corepressors", "it releases the corepressors and", "releases the corepressors and binds", "the corepressors and binds coactivators", "and binds coactivators cbp", "binds coactivators cbp src", "coactivators cbp src hat", "src hat complex asc", "hat complex asc complex", "asc complex and trap", "complex and trap mediator", "trap mediator complex which", "mediator complex which initiate", "complex which initiate transcription", "which initiate transcription of the", "initiate transcription of the target", "transcription of the target genes.
target", "of the target genes.
target genes", "the target genes.
target genes of", "target genes.
target genes of ppar", "genes.
target genes of ppar alpha", "genes of ppar alpha participate", "of ppar alpha participate in", "ppar alpha participate in fatty", "alpha participate in fatty acid", "participate in fatty acid transport", "fatty acid transport fatty", "acid transport fatty acid", "transport fatty acid oxidation", "fatty acid oxidation triglyceride", "acid oxidation triglyceride clearance", "triglyceride clearance lipoprotein production", "lipoprotein production and cholesterol", "production and cholesterol homeostasis." ] }, { "record_id": "GLY_000594_1_336", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "400511", "r hsa", "hsa 400511", "r hsa 400511" ] }, { "record_id": "GLY_000594_1_336", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "and inactivation", "inactivation of", "of glucose", "glucose dependent", "dependent insulinotropic", "insulinotropic polypeptide", "synthesis secretion", "secretion and", "and 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". progip", "progip is", "is cleaved", "cleaved in", "in secretory", "secretory granules", "granules by", "by prohormone", "prohormone convertase", "convertase 1", "at 2", "2 sites", "sites to", "to yield", "yield mature", "mature gip.", "gip. in", "in response", "response to", "to fat", "fat the", "the gip", "gip is", "is secreted", "secreted into", "into the", "the bloodstream.", "bloodstream. the", "the half", "half life", "life of", "of gip", "gip in", "in the", "the bloodstream", "bloodstream is", "is determined", "determined by", "by dipeptidyl", "dipeptidyl peptidase", "peptidase iv", "which cleaves", "cleaves 2", "2 amino", "amino acids", "acids at", "at the", "the amino", "amino terminus", "terminus of", "rendering it", "it biologically", "biologically inactive.", "in k cells", "k cells of", "cells of the", "of the intestine", "the intestine the", "intestine the transcription", "the transcription factors", "transcription factors pax6", "factors pax6 and", "pax6 and pdx", "and 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"the bloodstream is", "bloodstream is determined", "is determined by", "determined by dipeptidyl", "by dipeptidyl peptidase", "dipeptidyl peptidase iv", "iv which", "which cleaves 2", "cleaves 2 amino", "2 amino acids", "amino acids at", "acids at the", "at the amino", "the amino terminus", "amino terminus of", "terminus of gip", "gip rendering", "rendering it biologically", "it biologically inactive.", "in k cells of", "k cells of the", "cells of the intestine", "of the intestine the", "the intestine the transcription", "intestine the transcription factors", "the transcription factors pax6", "transcription factors pax6 and", "factors pax6 and pdx", "pax6 and pdx 1", "and pdx 1 activate", "pdx 1 activate transcription", "1 activate transcription of", "activate transcription of the", "transcription of the gene", "of the gene encoding", "the gene encoding glucose", "gene encoding glucose dependent", "encoding glucose dependent insulinotropic", "gip first called", "first called gastric inhibitory", "called gastric inhibitory peptide", "gastric inhibitory peptide .", "inhibitory peptide . progip", "peptide . progip is", ". progip is cleaved", "progip is cleaved in", "is cleaved in secretory", "cleaved in secretory granules", "in secretory granules by", "secretory granules by prohormone", "granules by prohormone convertase", "by prohormone convertase 1", "convertase 1 pc1", "pc1 at 2", "at 2 sites to", "2 sites to yield", "sites to yield mature", "to yield mature gip.", "yield mature gip. in", "mature gip. in response", "gip. in response to", "in response to fat", "response to fat the", "to fat the gip", "fat the gip is", "the gip is secreted", "gip is secreted into", "is secreted into the", "secreted into the bloodstream.", "into the bloodstream. the", "the bloodstream. the half", "bloodstream. the half life", "the half life of", "half life of gip", "life of gip in", "of gip in the", "gip in the bloodstream", "in the bloodstream is", "the bloodstream is determined", "bloodstream is determined by", "is determined by dipeptidyl", "determined by dipeptidyl peptidase", "by dipeptidyl peptidase iv", "peptidase iv which", "iv which cleaves", "which cleaves 2 amino", "cleaves 2 amino acids", "2 amino acids at", "amino acids at the", "acids at the amino", "at the amino terminus", "the amino terminus of", "amino terminus of gip", "of gip rendering", "gip rendering it", "rendering it biologically inactive.", "in k cells of the", "k cells of the intestine", "cells of the intestine the", "of the intestine the transcription", "the intestine the transcription factors", "intestine the transcription factors pax6", "the transcription factors pax6 and", "transcription factors pax6 and pdx", "factors pax6 and pdx 1", "pax6 and pdx 1 activate", "and pdx 1 activate transcription", "pdx 1 activate transcription of", "1 activate transcription of the", "activate transcription of the gene", "transcription of the gene encoding", "of the gene encoding glucose", "the gene encoding glucose dependent", "gene encoding glucose dependent insulinotropic", "encoding glucose dependent insulinotropic polypeptide", "polypeptide gip first", "gip first called gastric", "first called gastric inhibitory peptide", "called gastric inhibitory peptide .", "gastric inhibitory peptide . progip", "inhibitory peptide . progip is", "peptide . progip is cleaved", ". progip is cleaved in", "progip is cleaved in secretory", "is cleaved in secretory granules", "cleaved in secretory granules by", "in secretory granules by prohormone", "secretory granules by prohormone convertase", "granules by prohormone convertase 1", "prohormone convertase 1 pc1", "1 pc1 at", "pc1 at 2 sites", "at 2 sites to yield", "2 sites to yield mature", "sites to yield mature gip.", "to yield mature gip. in", "yield mature gip. in response", "mature gip. in response to", "gip. in response to fat", "in response to fat the", "response to fat the gip", "to fat the gip is", "fat the gip is secreted", "the gip is secreted into", "gip is secreted into the", "is secreted into the bloodstream.", "secreted into the bloodstream. the", "into the bloodstream. the half", "the bloodstream. the half life", "bloodstream. the half life of", "the half life of gip", "half life of gip in", "life of gip in the", "of gip in the bloodstream", "gip in the bloodstream is", "in the bloodstream is determined", "the bloodstream is determined by", "bloodstream is determined by dipeptidyl", "is determined by dipeptidyl peptidase", "determined by dipeptidyl peptidase iv", "dipeptidyl peptidase iv which", "peptidase iv which cleaves", "iv which cleaves 2", "which cleaves 2 amino acids", "cleaves 2 amino acids at", "2 amino acids at the", "amino acids at the amino", "acids at the amino terminus", "at the amino terminus of", "the amino terminus of gip", "terminus of gip rendering", "of gip rendering it", "gip rendering it biologically" ] }, { "record_id": "GLY_000594_1_337", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4043911", "r hsa", "hsa 4043911", "r hsa 4043911" ] }, { "record_id": "GLY_000594_1_337", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pmm2", "pmm2 causes", "causes pmm2", "pmm2 cdg", "defective pmm2 causes", "pmm2 causes pmm2", "causes pmm2 cdg", "defective pmm2 causes pmm2", "pmm2 causes pmm2 cdg", "defective pmm2 causes pmm2 cdg", "phosphomannomutase 2", "normally catalyses", "catalyses the", "the isomerisation", "isomerisation of", "of mannose", "mannose 6", "6 phosphate", "to mannose", "mannose 1", "1 phosphate", "in the", "the cytosol", "cytosol of", "of cells.", "cells. man1p", "man1p is", "is a", "a precursor", "precursor in", "the synthesis", "synthesis of", "of gdp", "gdp mannose", "mannose and", "and dolichol", "dolichol phosphate", "phosphate mannose", "required for", "for critical", "critical mannosyl", "mannosyl transfer", "transfer reactions", "reactions in", "the n", "n glycosylation", "glycosylation of", "of proteins.", "proteins. mutations", "mutations in", "the pmm2", "pmm2 gene", "gene are", "are one", "one of", "of the", "the causes", "causes of", "of jaeken", "jaeken syndrome", "a congenital", "congenital disorder", "disorder of", "of glycosylation", "glycosylation type", "type 1a", "previously cdg", "cdg 1a", "matthijs et", "et al.", "al. 1997", "1997 .", ". pmm2", "cdg was", "was first", "first described", "described in", "in belgian", "belgian identical", "identical twin", "twin sisters", "characterized by", "by psychomotor", "psychomotor retardation", "retardation and", "and multiple", "multiple serum", "serum glycoprotein", "glycoprotein abnormalities.", "abnormalities. serum", "serum and", "and csf", "csf transferrin", "transferrin were", "were found", "found to", "to be", "be deficient", "deficient in", "in sialic", "sialic acid", "jaeken et", "al. 1984", "1984 .", "cdg is", "is the", "the most", "most common", "common cdg", "cdg disease", "disease subtype.", "2 pmm2", "pmm2 normally", "normally catalyses the", "catalyses the isomerisation", "the isomerisation of", "isomerisation of mannose", "of mannose 6", "mannose 6 phosphate", "phosphate man6p", "man6p to", "to mannose 1", "mannose 1 phosphate", "phosphate man1p", "man1p in", "in the cytosol", "the cytosol of", "cytosol of cells.", "of cells. man1p", "cells. man1p is", "man1p is a", "is a precursor", "a precursor in", "precursor in the", "in the synthesis", "the synthesis of", "synthesis of gdp", "of gdp mannose", "gdp mannose and", "mannose and dolichol", "and dolichol phosphate", "dolichol phosphate mannose", "mannose required", "required for critical", "for critical mannosyl", "critical mannosyl transfer", "mannosyl transfer reactions", "transfer reactions in", "reactions in the", "in the n", "the n glycosylation", "n glycosylation of", "glycosylation of proteins.", "of proteins. mutations", "proteins. mutations in", "mutations in the", "in the pmm2", "the pmm2 gene", "pmm2 gene are", "gene are one", "are one of", "one of the", "of the causes", "the causes of", "causes of jaeken", "of jaeken syndrome", "syndrome a", "a congenital disorder", "congenital disorder of", "disorder of glycosylation", "of glycosylation type", "glycosylation type 1a", "1a pmm2", "cdg previously", "previously cdg 1a", "matthijs et al.", "et al. 1997", "al. 1997 .", "1997 . pmm2", ". pmm2 cdg", "pmm2 cdg was", "cdg was first", "was first described", "first described in", "described in belgian", "in belgian identical", "belgian identical twin", "identical twin sisters", "sisters characterized", "characterized by psychomotor", "by psychomotor retardation", "psychomotor retardation and", "retardation and multiple", "and multiple serum", "multiple serum glycoprotein", "serum glycoprotein abnormalities.", "glycoprotein abnormalities. serum", "abnormalities. serum and", "serum and csf", "and csf transferrin", "csf transferrin were", "transferrin were found", "were found to", "found to be", "to be deficient", "be deficient in", "deficient in sialic", "in sialic acid", "acid jaeken", "jaeken et al.", "et al. 1984", "al. 1984 .", "1984 . pmm2", "pmm2 cdg is", "cdg is the", "is the most", "the most common", "most common cdg", "common cdg disease", "cdg disease subtype.", "phosphomannomutase 2 pmm2", "pmm2 normally catalyses", "normally catalyses the isomerisation", "catalyses the isomerisation of", "the isomerisation of mannose", "isomerisation of mannose 6", "of mannose 6 phosphate", "6 phosphate man6p", "man6p to mannose", "to mannose 1 phosphate", "1 phosphate man1p", "man1p in the", "in the cytosol of", "the cytosol of cells.", "cytosol of cells. man1p", "of cells. man1p is", "cells. man1p is a", "man1p is a precursor", "is a precursor in", "a precursor in the", "precursor in the synthesis", "in the synthesis of", "the synthesis of gdp", "synthesis of gdp mannose", "of gdp mannose and", "gdp mannose and dolichol", "mannose and dolichol phosphate", "and dolichol phosphate mannose", "phosphate mannose required", "mannose required for", "required for critical mannosyl", "for critical mannosyl transfer", "critical mannosyl transfer reactions", "mannosyl transfer reactions in", "transfer reactions in the", "reactions in the n", "in the n glycosylation", "the n glycosylation of", "n glycosylation of proteins.", "glycosylation of proteins. mutations", "of proteins. mutations in", "proteins. mutations in the", "mutations in the pmm2", "in the pmm2 gene", "the pmm2 gene are", "pmm2 gene are one", "gene are one of", "are one of the", "one of the causes", "of the causes of", "the causes of jaeken", "causes of jaeken syndrome", "jaeken syndrome a", "syndrome a congenital", "a congenital disorder of", "congenital disorder of glycosylation", "disorder of glycosylation type", "of glycosylation type 1a", "type 1a pmm2", "1a pmm2 cdg", "pmm2 cdg previously", "cdg previously cdg", "1a matthijs", "matthijs et al. 1997", "et al. 1997 .", "al. 1997 . pmm2", "1997 . pmm2 cdg", ". pmm2 cdg was", "pmm2 cdg was first", "cdg was first described", "was first described in", "first described in belgian", "described in belgian identical", "in belgian identical twin", "belgian identical twin sisters", "twin sisters characterized", "sisters characterized by", "characterized by psychomotor retardation", "by psychomotor retardation and", "psychomotor retardation and multiple", "retardation and multiple serum", "and multiple serum glycoprotein", "multiple serum glycoprotein abnormalities.", "serum glycoprotein abnormalities. serum", "glycoprotein abnormalities. serum and", "abnormalities. serum and csf", "serum and csf transferrin", "and csf transferrin were", "csf transferrin were found", "transferrin were found to", "were found to be", "found to be deficient", "to be deficient in", "be deficient in sialic", "deficient in sialic acid", "sialic acid jaeken", "acid jaeken et", "jaeken et al. 1984", "et al. 1984 .", "al. 1984 . pmm2", "1984 . pmm2 cdg", ". pmm2 cdg is", "pmm2 cdg is the", "cdg is the most", "is the most common", "the most common cdg", "most common cdg disease", "common cdg disease subtype.", "2 pmm2 normally", "pmm2 normally catalyses the", "normally catalyses the isomerisation of", "catalyses the isomerisation of mannose", "the isomerisation of mannose 6", "isomerisation of mannose 6 phosphate", "mannose 6 phosphate man6p", "phosphate man6p to", "man6p to mannose 1", "mannose 1 phosphate man1p", "phosphate man1p in", "man1p in the cytosol", "in the cytosol of cells.", "the cytosol of cells. man1p", "cytosol of cells. man1p is", "of cells. man1p is a", "cells. man1p is a precursor", "man1p is a precursor in", "is a precursor in the", "a precursor in the synthesis", "precursor in the synthesis of", "in the synthesis of gdp", "the synthesis of gdp mannose", "synthesis of gdp mannose and", "of gdp mannose and dolichol", "gdp mannose and dolichol phosphate", 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can", "q can stimulate the", "can stimulate the activation of", "stimulate the activation of burton", "the activation of burton tyrosine", "activation of burton tyrosine kinase", "burton tyrosine kinase ma", "tyrosine kinase ma y", "kinase ma y c", "ma y c et al.", "y c et al. 1998", "c et al. 1998 .", "et al. 1998 . regulator", "al. 1998 . regulator of", "1998 . regulator of g", ". regulator of g protein", "regulator of g protein signalling", "g protein signalling rgs", "signalling rgs proteins", "rgs proteins can regulate", "proteins can regulate the activity", "can regulate the activity of", "regulate the activity of g", "the activity of g alpha", "of g alpha z", "z soundararajan m", "soundararajan m et al. 2008", "m et al. 2008 ." ] }, { "record_id": "GLY_000594_1_343", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "416482", "r hsa", "hsa 416482", "r hsa 416482" ] }, { "record_id": "GLY_000594_1_343", "filename": 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induced vascular", "induced vascular smooth muscle", "vascular smooth muscle relaxation", "muscle relaxation furchgott", "relaxation furchgott and", "furchgott and vanhoutte 1989", "and vanhoutte 1989 .", "vanhoutte 1989 . phosphodiesterase", "1989 . phosphodiesterase 5", "phosphodiesterase 5 pde5", "pde5 hydrolyzes cgmp", "hydrolyzes cgmp the", "cgmp the pde5", "the pde5 inhibitor sildenafil", "inhibitor sildenafil viagra", "viagra increases intracellular", "increases intracellular cgmp and", "intracellular cgmp and thereby", "cgmp and thereby can", "and thereby can be", "thereby can be used", "can be used as", "be used as a", "used as a treatment", "as a treatment for", "a treatment for erectile", "treatment for erectile dysfunction", "erectile dysfunction corbin", "dysfunction corbin and", "corbin and francis 1999", "and francis 1999 .", "francis 1999 . the", "1999 . the role", ". the role of", "the role of the", "role of the cgmp", "of the cgmp and", "the cgmp and pkg", "cgmp and 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proposed", "have been proposed to", "been proposed to be", "proposed to be biphasic", "be biphasic consisting", "biphasic consisting of", "consisting of an early", "of an early stimulatory", "an early stimulatory response", "early stimulatory response that", "stimulatory response that promotes", "response that promotes platelet", "that promotes platelet activation", "promotes platelet activation followed", "platelet activation followed by", "activation followed by a", "followed by a delayed", "by a delayed platelet", "a delayed platelet inhibition", "delayed platelet inhibition that", "platelet inhibition that serves", "inhibition that serves to", "that serves to limit", "serves to limit the", "to limit the size", "limit the size of", "the size of platelet", "size of platelet aggregates", "aggregates li", "li et al 2003", "et al 2003 .", "cyclic guanosine monophosphate cgmp", "monophosphate cgmp is", "cgmp is an important", "is an important secondary messenger", "an important secondary messenger synthesized", "important secondary messenger synthesized by", "secondary messenger synthesized by guanylate", "messenger synthesized by guanylate cyclases.", "synthesized by guanylate cyclases. cgmp", "by guanylate cyclases. cgmp has", "guanylate cyclases. cgmp has effects", "cyclases. cgmp has effects on", "cgmp has effects on phosphodiesterases", "effects on phosphodiesterases pde", "pde ion gated", "ion gated channels and", "gated channels and the", "channels and the cgmp", "and the cgmp dependent protein", "the cgmp dependent protein kinases", "dependent protein kinases cgk", "kinases cgk protein", "cgk protein kinase g", "protein kinase g or pkg", "kinase g or pkg .", "g or pkg . it", "or pkg . it is", "pkg . it is involved", ". it is involved in", "it is involved in regulation", "is involved in regulation of", "in regulation of several", "regulation of several physiological", "of several physiological functions", "several physiological functions including vasodilation", "functions including vasodilation platelet", "including vasodilation platelet aggregation", "vasodilation platelet aggregation and", "aggregation and neurotransmission. elevation", "and neurotransmission. elevation of", "neurotransmission. elevation of intracellular", "elevation of intracellular cgmp activates", "of intracellular cgmp activates pkg", "cgmp activates pkg haslam", "activates pkg haslam et", "pkg haslam et al.", "et al. 1999 which", "al. 1999 which regulates", "1999 which regulates several", "which regulates several intracellular molecules", "regulates several intracellular molecules and", "several intracellular molecules and pathways", "intracellular molecules and pathways including", "molecules and pathways including the", "and pathways including the vasodilator", "pathways including the vasodilator stimulated", "including the vasodilator stimulated phosphoprotein", "vasodilator stimulated phosphoprotein vasp", "vasp halbrugge et", "et al. 1990 and", "al. 1990 and the", "1990 and the erk", "the erk pathway hood", "erk pathway hood and", "pathway hood and granger", "and granger 1998 li", "granger 1998 li et", "1998 li et al.", "li et al. 2001 .", "et al. 2001 . cgmp", "al. 2001 . cgmp mediates", "2001 . cgmp mediates nitric", ". cgmp mediates nitric oxide", "mediates nitric oxide no", "oxide no induced", "no induced vascular smooth", "induced vascular smooth muscle relaxation", "smooth muscle relaxation furchgott", "muscle relaxation furchgott and", "relaxation furchgott and vanhoutte", "furchgott and vanhoutte 1989 .", "and vanhoutte 1989 . phosphodiesterase", "vanhoutte 1989 . phosphodiesterase 5", ". phosphodiesterase 5 pde5", "5 pde5 hydrolyzes", "hydrolyzes cgmp the pde5", "cgmp the pde5 inhibitor", "pde5 inhibitor sildenafil viagra", "sildenafil viagra increases", "viagra increases intracellular cgmp", "increases intracellular cgmp and thereby", "intracellular cgmp and thereby can", "cgmp and thereby can be", "and thereby can be used", "thereby 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the", "primary barrier to the diffusion", "barrier to the diffusion of", "to the diffusion of solutes", "the diffusion of solutes through", "diffusion of solutes through the", "of solutes through the paracellular", "solutes through the paracellular space", "the paracellular space barrier", "paracellular space barrier function", "barrier function tsukita", "function tsukita et", "tsukita et al. 2001", "et al. 2001 .", "al. 2001 . they", "2001 . they also prevent", ". they also prevent the", "they also prevent the intermixing", "also prevent the intermixing of", "prevent the intermixing of intramembrane", "the intermixing of intramembrane proteins", "intermixing of intramembrane proteins and", "of intramembrane proteins and lipids", "intramembrane proteins and lipids and", "proteins and lipids and thus", "and lipids and thus create", "lipids and thus create a", "and thus create a boundary", "thus create a boundary between", "create a boundary between the", "a boundary between the 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"major molecular interactions responsible for", "molecular interactions responsible for the", "interactions responsible for the formation", "responsible for the formation of", "for the formation of tj", "the formation of tj strands", "formation of tj strands and", "of tj strands and for", "tj strands and for the", "strands and for the rectruitment", "and for the rectruitment of", "for the rectruitment of the", "the rectruitment of the par", "rectruitment of the par 3", "of the par 3 pkc", "the par 3 pkc par", "par 3 pkc par 6", "3 pkc par 6 and", "pkc par 6 and crb3", "par 6 and crb3 pals1", "6 and crb3 pals1 patj", "and crb3 pals1 patj complexes", "crb3 pals1 patj complexes that", "pals1 patj complexes that function", "patj complexes that function in", "complexes that function in tight", "that function in tight junction", "function in tight junction formation", "tight junction formation ebnet", "formation ebnet 2008" ] }, { "record_id": "GLY_000594_1_358", "filename": 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protein", "coupled receptors that", "receptors that include", "that include the", "include the metabotropic", "the metabotropic glutamate", "metabotropic glutamate receptors", "glutamate receptors and", "receptors and several", "and several additional", "several additional receptors", "receptors brauner", "brauner osborne h", "osborne h et", "h et al", "al 2007", "2007 . family", ". family c", "family c gpcrs", "c gpcrs have", "gpcrs have a", "have a large", "a large extracellular", "large extracellular n", "extracellular n terminus", "n terminus which", "terminus which binds", "which binds the", "binds the orthosteric", "orthosteric endogenous", "endogenous ligand.", "ligand. the shape", "the shape of", "shape of this", "of this domain", "this domain is", "domain is often", "is often likened", "often likened to", "likened to a", "to a clam.", "a clam. several", "clam. several allosteric", "several allosteric ligands", "allosteric ligands to", "ligands to these", "to these receptors", "these receptors have", "receptors have been", "have been identified", "been identified and", "identified and these", "and these bind", "these bind within", "bind within the", "within the seven", "the seven transmembrane", "seven transmembrane region.", "the class c g", "class c g protein", "c g protein coupled", "g protein coupled receptors", "protein coupled receptors are", "coupled receptors are a", "receptors are a class", "are a class of", "a class of g", "class of g protein", "of g protein coupled", "protein coupled receptors that", "coupled receptors that include", "receptors that include the", "that include the metabotropic", "include the metabotropic glutamate", "the metabotropic glutamate receptors", "metabotropic glutamate receptors and", "glutamate receptors and several", "receptors and several additional", "and several additional receptors", "additional receptors brauner", "receptors brauner osborne", "brauner osborne h et", "osborne h et al", "et al 2007", "al 2007 .", "2007 . family c", ". family c gpcrs", "family c gpcrs have", "c gpcrs have a", "gpcrs have a large", "have a large extracellular", "a large extracellular n", "large extracellular n terminus", "extracellular n terminus which", "n terminus which binds", "terminus which binds the", "which binds the orthosteric", "the orthosteric endogenous", "endogenous ligand. the", "ligand. the shape of", "the shape of this", "shape of this domain", "of this domain is", "this domain is often", "domain is often likened", "is often likened to", "often likened to a", "likened to a clam.", "to a clam. several", "a clam. several allosteric", "clam. several allosteric ligands", "several allosteric ligands to", "allosteric ligands to these", "ligands to these receptors", "to these receptors have", "these receptors have been", "receptors have been identified", "have been identified and", "been identified and these", "identified and these bind", "and these bind within", "these bind within the", "bind within the seven", "within the seven transmembrane", "the seven transmembrane region.", "the class c g protein", "class c g protein coupled", "c g protein coupled receptors", "g protein coupled receptors are", "protein coupled receptors are a", "coupled receptors are a class", "receptors are a class of", "are a class of g", "a class of g protein", "class of g protein coupled", "of g protein coupled receptors", "g protein coupled receptors that", "protein coupled receptors that include", "coupled receptors that include the", "receptors that include the metabotropic", "that include the metabotropic glutamate", "include the metabotropic glutamate receptors", "the metabotropic glutamate receptors and", "metabotropic glutamate receptors and several", "glutamate receptors and several additional", "receptors and several additional receptors", "several additional receptors brauner", "additional receptors brauner osborne", "receptors brauner osborne h", "brauner osborne h et al", "h et al 2007", "et al 2007 .", "al 2007 . family", "2007 . family c gpcrs", ". family c gpcrs have", "family c gpcrs have a", "c gpcrs have a large", "gpcrs have a large extracellular", "have a large extracellular n", "a large extracellular n terminus", "large extracellular n terminus which", "extracellular n terminus which binds", "n terminus which binds the", "terminus which binds the orthosteric", "binds the orthosteric endogenous", "orthosteric endogenous ligand.", "endogenous ligand. the shape", "ligand. the shape of this", "the shape of this domain", "shape of this domain is", "of this domain is often", "this domain is often likened", "domain is often likened to", "is often likened to a", "often likened to a clam.", "likened to a clam. several", "to a clam. several allosteric", "a clam. several allosteric ligands", "clam. several allosteric ligands to", "several allosteric ligands to these", "allosteric ligands to these receptors", "ligands to these receptors have", "to these receptors have been", "these receptors have been identified", "receptors have been identified and", "have been identified and these", "been identified and these bind", "identified and these bind within", "and these bind within the", "these bind within the seven", "bind within the seven transmembrane", "within the seven transmembrane region." ] }, { "record_id": "GLY_000594_1_360", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "422356", "r hsa", "hsa 422356", "r hsa 422356" ] }, { "record_id": "GLY_000594_1_360", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of insulin", "insulin secretion", "regulation of insulin", "of insulin secretion", "regulation of insulin secretion", "pancreatic beta", "beta cells", "cells integrate", "integrate signals", "signals from", "from several", "several metabolites", "metabolites and", "and hormones", "hormones to", "to control", "control the", "the secretion", 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increased", "noradrenaline.

increased blood", "blood glucose", "glucose levels", "levels from", "from dietary", "dietary carbohydrate", "carbohydrate play", "play a", "a dominant", "dominant role", "role in", "in insulin", "insulin release", "release from", "from the", "the beta", "cells of", "of the", "the pancreas.", "pancreas. glucose", "glucose catabolism", "catabolism in", "in the", "beta cell", "cell is", "is the", "the transducer", "transducer that", "that links", "links increased", "increased glucose", "levels to", "to insulin", "insulin release.", "release. glucose", "glucose uptake", "uptake and", "and glycolysis", "glycolysis generate", "generate cytosolic", "cytosolic pyruvate", "pyruvate is", "is transported", "transported to", "to mitochondria", "mitochondria and", "and converted", "converted both", "both to", "to oxaloacetate", "oxaloacetate which", "which increases", "increases levels", "levels of", "of tca", "tca cycle", "cycle intermediates", "and to", "to acetyl", "acetyl coa", "coa which", "which is", "is oxidized", "oxidized to", "to co2", "co2 via", "via the", "the tca", "tca cycle.", "cycle. the", "the rates", "rates of", "of atp", "atp synthesis", "synthesis and", "and transport", "transport to", "to the", "the cytosol", "cytosol increase", "plasma membrane", "membrane atp", "atp sensitive", "sensitive inward", "inward rectifying", "rectifying potassium", "potassium channels", "katp channels", "the membrane", "membrane depolarizes", "and voltage", "voltage gated", "gated calcium", "calcium channels", "channels in", "membrane open", "muoio and", "and newgard", "newgard 2008", "wiederkehr and", "and wollheim", "wollheim 2006", "2006 .

elevated", ".

elevated calcium", "calcium concentrations", "concentrations near", "near the", "the plasma", "membrane cause", "cause insulin", "secretion in", "in two", "two phases:", "phases: an", "an initial", "initial high", "high rate", "rate within", "within minutes", "minutes of", "of glucose", "glucose stimulation", "stimulation and", "and a", "a slow", "sustained release", "release lasting", "lasting longer", "longer than", "than 30", "30 minutes.", "minutes. in", "the initial", "initial phase", "50 100", "100 insulin", "insulin granules", "granules already", "already docked", "docked at", "at the", "membrane are", "are exocytosed.", "exocytosed. exocytosis", "exocytosis is", "is rendered", "rendered calcium", "calcium dependent", "dependent by", "by synaptotagmin", "synaptotagmin v/ix", "a calcium", "calcium binding", "binding membrane", "membrane protein", "protein located", "located in", "membrane of", "the docked", "docked granule", "although the", "the exact", "exact action", "action of", "of synapototagmin", "synapototagmin in", "to calcium", "calcium is", "is unknown.", "unknown. calcium", "calcium also", "also causes", "causes a", "a translocation", "translocation of", "of reserve", "reserve granules", "granules within", "within the", "the cell", "cell towards", "towards the", "membrane for", "for release", "release in", "the second", "sustained phase", "phase of", "of secretion.", "secretion. human", "human cells", "cells contain", "contain l", "l type", "continually reopening", "p/q type", "long burst", "r type", "and t", "t type", "short burst", "channels and", "and these", "these partly", "partly account", "account for", "for differences", "differences between", "between the", "the two", "two phases", "phases of", "secretion. other", "factors that", "that distinguish", "distinguish the", "phases are", "are not", "not yet", "yet fully", "fully known", "bratanova tochkova", "tochkova et", "et al.", "al. 2002", "henquin 2000", "macdonald et", "al. 2005", "2005 .", "pancreatic beta cells", "beta cells integrate", "cells integrate signals", "integrate signals from", "signals from several", "from several metabolites", "several metabolites and", "metabolites and hormones", "and hormones to", "hormones to control", "to control the", "control the secretion", "the secretion of", "secretion of insulin.", "of insulin. in", "insulin. in general", "general glucose", "glucose triggers insulin", "triggers insulin secretion", "insulin secretion while", "secretion while other", "while other factors", "other factors can", "factors can amplify", "can amplify or", "amplify or inhibit", "or inhibit the", "inhibit the amount", "the amount of", "amount of insulin", "of insulin secreted", "insulin secreted in", "secreted in response", "in response to", "response to glucose.", "to glucose. factors", "glucose. factors which", "factors which increase", "which increase insulin", "increase insulin secretion", "insulin secretion include", "secretion include the", "include the incretin", "the incretin hormones", "incretin hormones glucose", "hormones glucose dependent", "glucose dependent insulinotropic", "dependent insulinotropic polypeptide", "polypeptide gip", "gip and glucagon", "and glucagon like", "glucagon like peptide", "like peptide 1", "1 glp", "acetylcholine and", "and fatty acids.", "fatty acids. factors", "acids. factors which", "factors which inhibit", "which inhibit insulin", "inhibit insulin secretion", "secretion include adrenaline", "include adrenaline and", "adrenaline and noradrenaline.

increased", "and noradrenaline.

increased blood", "noradrenaline.

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elevated", "2006 .

elevated calcium", ".

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elevated", "wollheim 2006 .

elevated calcium", "2006 .

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already", "insulin granules already docked", "granules already docked at", "already docked at the", "docked at the membrane", "at the membrane are", "the membrane are exocytosed.", "membrane are exocytosed. exocytosis", "are exocytosed. exocytosis is", "exocytosed. exocytosis is rendered", "exocytosis is rendered calcium", "is rendered calcium dependent", "rendered calcium dependent by", "calcium dependent by synaptotagmin", "dependent by synaptotagmin v/ix", "synaptotagmin v/ix a", "v/ix a calcium", "a calcium binding membrane", "calcium binding membrane protein", "binding membrane protein located", "membrane protein located in", "protein located in the", "located in the membrane", "in the membrane of", "the membrane of the", "membrane of the docked", "of the docked granule", "docked granule although", "granule although the", "although the exact action", "the exact action of", "exact action of synapototagmin", "action of synapototagmin in", "of synapototagmin in response", "synapototagmin in response to", "in response to calcium", "response to calcium is", "to calcium is unknown.", "calcium is unknown. calcium", "is unknown. calcium also", "unknown. calcium also causes", "calcium also causes a", "also causes a translocation", "causes a translocation of", "a translocation of reserve", "translocation of reserve granules", "of reserve granules within", "reserve granules within the", "granules within the cell", "within the cell towards", "the cell towards the", "cell towards the plasma", "towards the plasma membrane", "the plasma membrane for", "plasma membrane for release", "membrane for release in", "for release in the", "release in the second", "the second sustained", "second sustained phase", "sustained phase of secretion.", "phase of secretion. human", "of secretion. human cells", "secretion. human cells contain", "human cells contain l", "cells contain l type", "l type continually", "type continually reopening", "reopening p/q", "p/q type long", "type long burst", "burst r", "r type long", "burst and", "t type short", "type short burst", "short burst calcium", "burst calcium channels", "calcium channels and these", "channels and these partly", "and these partly account", "these partly account for", "partly account for differences", "account for differences between", "for differences between the", "differences between the two", "between the two phases", "the two phases of", "two phases of secretion.", "phases of secretion. other", "of secretion. other factors", "secretion. other factors that", "other factors that distinguish", "factors that distinguish the", "that distinguish the two", "distinguish the two phases", "the two phases are", "two phases are not", "phases are not yet", "are not yet fully", "not yet fully known", "fully known bratanova", "known bratanova tochkova", "bratanova tochkova et al.", "tochkova et al. 2002", "al. 2002 henquin", "2002 henquin 2000", "henquin 2000 macdonald", "2000 macdonald et", "macdonald et al. 2005", "et al. 2005 .", "pancreatic beta cells integrate signals", "beta cells integrate signals from", "cells integrate signals from several", "integrate signals from several metabolites", "signals from several metabolites and", "from several metabolites and hormones", "several metabolites and hormones to", "metabolites and hormones to control", "and hormones to control the", "hormones to control the secretion", "to control the secretion of", "control the secretion of insulin.", "the secretion of insulin. in", "secretion of insulin. in general", "insulin. in general glucose", "in general glucose triggers", "general glucose triggers insulin", "glucose triggers insulin secretion while", "triggers insulin secretion while other", "insulin secretion while other factors", "secretion while other factors can", "while other factors can amplify", "other factors can amplify or", "factors can amplify or inhibit", "can amplify or inhibit the", "amplify or inhibit the amount", "or inhibit the amount of", "inhibit the amount of insulin", "the amount of insulin secreted", "amount of insulin secreted in", "of insulin secreted in response", "insulin secreted in response to", "secreted in response to glucose.", "in response to glucose. factors", "response to glucose. factors which", "to glucose. factors which increase", "glucose. factors which increase insulin", "factors which increase insulin secretion", "which increase insulin secretion include", "increase insulin secretion include the", "insulin secretion include the incretin", "secretion include the incretin hormones", "include the incretin hormones glucose", "the incretin hormones glucose dependent", "incretin hormones glucose dependent insulinotropic", "hormones glucose dependent insulinotropic polypeptide", "dependent insulinotropic polypeptide gip", "insulinotropic polypeptide gip and", "polypeptide gip and glucagon", "gip and glucagon like peptide", "and glucagon like peptide 1", "like peptide 1 glp", "peptide 1 glp 1", "glp 1 acetylcholine", "acetylcholine and fatty acids.", "and fatty acids. factors which", "fatty acids. factors which inhibit", "acids. factors which inhibit insulin", "factors which inhibit insulin secretion", "which inhibit insulin secretion include", "inhibit insulin secretion include adrenaline", "insulin secretion include adrenaline and", "secretion include adrenaline and noradrenaline.

increased", "include adrenaline and noradrenaline.

increased blood", "adrenaline and noradrenaline.

increased blood glucose", "and noradrenaline.

increased blood glucose levels", "noradrenaline.

increased blood glucose levels from", "blood glucose levels from dietary", "glucose levels from dietary carbohydrate", "levels from dietary carbohydrate play", "from dietary carbohydrate play a", "dietary carbohydrate play a dominant", "carbohydrate play a dominant role", "play a dominant role in", "a dominant role in insulin", "dominant role in insulin release", "role in insulin release from", "in insulin release from the", "insulin release from the beta", "release from the beta cells", "from the beta cells of", "the beta cells of the", "beta cells of the pancreas.", "cells of the pancreas. glucose", "of the pancreas. glucose catabolism", "the pancreas. glucose catabolism in", "pancreas. glucose catabolism in the", "glucose catabolism in the beta", "catabolism in the beta cell", "in the beta cell is", "the beta cell is the", "beta cell is the transducer", "cell is the transducer that", "is the transducer that links", "the transducer that links increased", "transducer that links increased glucose", "that links increased glucose levels", "links increased glucose levels to", "increased glucose levels to insulin", "glucose levels to insulin release.", "levels to insulin release. glucose", "to insulin release. glucose uptake", "insulin release. glucose uptake and", "release. glucose uptake and glycolysis", "glucose uptake and glycolysis generate", "uptake and glycolysis generate cytosolic", "and glycolysis generate cytosolic pyruvate", "generate cytosolic pyruvate pyruvate", "cytosolic pyruvate pyruvate is", "pyruvate pyruvate is transported", "pyruvate is transported to mitochondria", "is transported to mitochondria and", "transported to mitochondria and converted", "to mitochondria and converted both", "mitochondria and converted both to", "and converted both to oxaloacetate", "converted both to oxaloacetate which", "both to oxaloacetate which increases", "to oxaloacetate which increases levels", "oxaloacetate which increases levels of", "which increases levels of tca", "increases levels of tca cycle", "levels of tca cycle intermediates", "tca cycle intermediates and", "cycle intermediates and to", "intermediates and to acetyl", "and to acetyl coa which", "to acetyl coa which is", "acetyl coa which is oxidized", "coa which is oxidized to", "which is oxidized to co2", "is oxidized to co2 via", "oxidized to co2 via the", "to co2 via the tca", "co2 via the tca cycle.", "via the tca cycle. the", "the tca cycle. the rates", "tca cycle. the rates of", "cycle. the rates of atp", "the rates of atp synthesis", "rates of atp synthesis and", "of atp synthesis and transport", "atp synthesis and transport to", "synthesis and transport to the", "and transport to the cytosol", "transport to the cytosol increase", "the cytosol increase plasma", "cytosol increase plasma membrane", "increase plasma membrane atp", "plasma membrane atp sensitive inward", "membrane atp sensitive inward rectifying", "atp sensitive inward rectifying potassium", "sensitive inward rectifying potassium channels", "rectifying potassium channels katp", "potassium channels katp channels", "channels close the", "close the membrane depolarizes", "the membrane depolarizes and", "membrane depolarizes and voltage", "depolarizes and voltage gated", "and voltage gated calcium channels", "voltage gated calcium channels in", "gated calcium channels in the", "calcium channels in the membrane", "channels in the membrane open", "the membrane open muoio", "membrane open muoio and", "open muoio and newgard", "and newgard 2008 wiederkehr", "newgard 2008 wiederkehr and", "2008 wiederkehr and wollheim", "wiederkehr and wollheim 2006 .

elevated", "and wollheim 2006 .

elevated calcium", "wollheim 2006 .

elevated calcium concentrations", "2006 .

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"sodium ion and", "ion and protons", "protons orlowski", "orlowski j and", "j and grinstein", "and grinstein s", "s 2004", "slc12 functions as", "functions as na+", "na+ k+", "k+ and cl", "cl ion", "ion electroneutral symporters", "symporters hebert", "hebert sc et", "sc et al", "slc26 is the", "is the trans", "the trans epithelial", "trans epithelial multifunctional", "epithelial multifunctional anion", "anion e.g.", "sulfate oxalate", "oxalate hco", "family important", "important in cartilage", "in cartilage development", "development production", "production of thyroid", "of thyroid hormone", "hormone sound", "sound amplification in", "amplification in the", "in the cochlea", "the cochlea etc", "etc sindic", "sindic a et", "a et al", "al 2007", "2007 dorwart", "dorwart mr et", "mr et al", "al 2008", "2008 ashmore", "j 2008", "2008 . slc34", ". slc34 is", "slc34 is an", "is an important", "an important type", "important type ii", "type ii na+/", "ii na+/ hpo4", "na+/ hpo4 2", "2 symporter", "symporter forster", "forster ic et", "ic et al", "al 2006", "2006 virkki", "virkki lv et", "lv et al", "slc20 was originally", "was originally identified", "originally identified as", "identified as a", "as a viral", "a viral receptor", "receptor and", "and functions as", "functions as a", "as a type", "a type iii", "type iii na+/", "iii na+/ h2po4", "symporter collins", "collins jf et", "jf et al", "2004 virkki", "2007 . eight", "eight slc", "slc gene families", "gene families are", "families are involved", "are involved in", "in the transport", "the transport of", "transport of amino", "of amino acids", "amino acids and", "acids and oligopeptides.", "teleologically one might", "one might argue that", "might argue that inorganic", "argue that inorganic cation", "that inorganic cation and", "inorganic cation and anion", "cation and anion transport", "and anion transport would", "anion transport would be", "transport would be evolutionarily", "would be evolutionarily among", "be evolutionarily among the", "evolutionarily among the oldest", "among the oldest transport", "the oldest transport functions.", "oldest transport functions. eight", "transport functions. eight families", "functions. eight families comprise", "eight families comprise the", "families comprise the group", "comprise the group that", "the group that transports", "group that transports exclusively", "that transports exclusively inorganic", "transports exclusively inorganic cations", "exclusively inorganic cations and", "inorganic cations and anions", "cations and anions across", "and anions across membranes", "anions across membranes :", "across membranes : slc4", "membranes : slc4 plays", ": slc4 plays a", "slc4 plays a pivotal", "plays a pivotal role", "a pivotal role in", "pivotal role in mediating", "role in mediating na+", "na+ and/or", "cl dependent", "dependent transport of basic", "transport of basic anions", "basic anions e.g.", "anions e.g. hco3", "2 in", "in various tissues and", "various tissues and cell", "tissues and cell types", "cell types in", "types in addition", "in addition to ph", "addition to ph regulation", "ph regulation specific", "regulation specific members", "specific members of this", "members of this family", "of this family also", "this family also contribute", "family also contribute to", "also contribute to vectorial", "contribute to vectorial trans", "to vectorial trans epithelial", "vectorial trans epithelial base", "trans epithelial base transport", "epithelial base transport in", "base transport in several", "transport in several organ", "in several organ systems", "several organ systems including", "organ systems including the", "systems including the kidney", "the kidney pancreas", "pancreas and eye", "eye pushkin", "pushkin a and kurtz", "a and kurtz i", "kurtz i 2006", "slc8 is a group", "is a group of", "a group of na+/ca2+", "group of na+/ca2+ exchangers", "na+/ca2+ exchangers slc8a1", "exchangers slc8a1 is", "slc8a1 is involved in", "is involved in cardiac", "involved in cardiac contractility", "contractility quednau", "quednau bd et al", "et al 2004", "2004 slc24", "slc24 is a group", "group of na+/ca2+ or", "of na+/ca2+ or na+/k+", "na+/ca2+ or na+/k+ exchangers", "na+/k+ exchangers altimimi", "exchangers altimimi hf", "altimimi hf and schnetkamp", "hf and schnetkamp pp", "schnetkamp pp 2007", "2007 slc9", "slc9 comprises na+/h+ exchanger", "comprises na+/h+ exchanger proteins", "na+/h+ exchanger proteins involved", "exchanger proteins involved in", "proteins involved in the", "involved in the electroneutral", "in the electroneutral exchange", "the electroneutral exchange of", "electroneutral exchange of sodium", "exchange of sodium ion", "of sodium ion and", "sodium ion and protons", "and protons orlowski", "protons orlowski j", "orlowski j and grinstein", "j and grinstein s", "grinstein s 2004", "2004 slc12", "slc12 functions as na+", "as na+ k+", "na+ k+ and", "and cl ion", "cl ion electroneutral", "electroneutral symporters hebert", "symporters hebert sc", "hebert sc et al", "2004 slc26", "slc26 is the trans", "is the trans epithelial", "the trans epithelial multifunctional", "trans epithelial multifunctional anion", "multifunctional anion e.g.", "anion e.g. sulfate", "e.g. sulfate oxalate", "hco cl", "cl exchanger", "exchanger family important", "family important in", "important in cartilage development", "cartilage development production", "development production of", "production of thyroid hormone", "thyroid hormone sound", "hormone sound amplification", "sound amplification in the", "amplification in the cochlea", "in the cochlea etc", "cochlea etc sindic", "etc sindic a", "sindic a et al", "et al 2007", "2007 dorwart mr", "dorwart mr et al", "et al 2008", "2008 ashmore j", "ashmore j 2008", "j 2008 .", "2008 . slc34 is", ". slc34 is an", "slc34 is an important", "is an important type", "an important type ii", "important type ii na+/", "type ii na+/ hpo4", "ii na+/ hpo4 2", "hpo4 2 symporter", "symporter forster ic", "forster ic et al", "et al 2006", "2006 virkki lv", "virkki lv et al", "2007 slc20", "slc20 was originally identified", "was originally identified as", "originally identified as a", "identified as a viral", "as a viral receptor", "viral receptor and", "receptor and functions", "and functions as a", "functions as a type", "as a type iii", "a type iii na+/", "type iii na+/ h2po4", "h2po4 symporter", "symporter collins jf", "collins jf et al", "2004 virkki lv", "al 2007 .", ". eight slc", "eight slc gene", "slc gene families are", "gene families are involved", "families are involved in", "are involved in the", "involved in the transport", "in the transport of", "the transport of amino", "transport of amino acids", "of amino acids and", "amino acids and oligopeptides.", "teleologically one might argue", "one might argue that inorganic", "might argue that inorganic cation", "argue that inorganic cation and", "that inorganic cation and anion", "inorganic cation and anion transport", "cation and anion transport would", "and anion transport would be", "anion transport would be evolutionarily", "transport would be evolutionarily among", "would be evolutionarily among the", "be evolutionarily among the oldest", "evolutionarily among the oldest transport", "among the oldest transport functions.", "the oldest transport functions. eight", "oldest transport functions. eight families", "transport functions. eight families comprise", "functions. eight families comprise the", "eight families comprise the group", "families comprise the group that", "comprise the group that transports", "the group that transports exclusively", "group that transports exclusively inorganic", "that transports exclusively inorganic cations", "transports exclusively inorganic cations and", "exclusively inorganic cations and anions", "inorganic cations and anions across", "cations and anions across membranes", "and anions across membranes :", "anions across membranes : slc4", "across membranes : slc4 plays", "membranes : slc4 plays a", ": slc4 plays a pivotal", "slc4 plays a pivotal role", "plays a pivotal role in", "a pivotal role in mediating", "pivotal role in mediating na+", "mediating na+ and/or", "na+ and/or cl", "and/or cl dependent", "cl dependent transport", "dependent transport of basic anions", "of basic anions e.g.", "basic anions e.g. hco3", "hco3 co3", "co3 2 in", "2 in various", "in various tissues and cell", "various tissues and cell types", "and cell types in", "cell types in addition", "types in addition to", "in addition to ph regulation", "to ph regulation specific", "ph regulation specific members", "regulation specific members of", "specific members of this family", "members of this family also", "of this family also contribute", "this family also contribute to", "family also contribute to vectorial", "also contribute to vectorial trans", "contribute to vectorial trans epithelial", "to vectorial trans epithelial base", "vectorial trans epithelial base transport", "trans epithelial base transport in", "epithelial base transport in several", "base transport in several organ", "transport in several organ systems", "in several organ systems including", "several organ systems including the", "organ systems including the kidney", "including the kidney pancreas", "kidney pancreas and", "and eye pushkin", "eye pushkin a", "pushkin a and kurtz i", "and kurtz i 2006", "2006 slc8", "slc8 is a group of", "is a group of na+/ca2+", "a group of na+/ca2+ exchangers", "of na+/ca2+ exchangers slc8a1", "na+/ca2+ exchangers slc8a1 is", "exchangers slc8a1 is involved", "slc8a1 is involved in cardiac", "is involved in cardiac contractility", "cardiac contractility quednau", "contractility quednau bd", "bd et al 2004", "2004 slc24 is", "slc24 is a group of", "a group of na+/ca2+ or", "group of na+/ca2+ or na+/k+", "of na+/ca2+ or na+/k+ exchangers", "or na+/k+ exchangers altimimi", "na+/k+ exchangers altimimi hf", "exchangers altimimi hf and", "altimimi hf and schnetkamp pp", "and schnetkamp pp 2007", "2007 slc9 comprises", "slc9 comprises na+/h+ exchanger proteins", "comprises na+/h+ exchanger proteins involved", "na+/h+ exchanger proteins involved in", "exchanger proteins involved in the", "proteins involved in the electroneutral", "involved in the electroneutral exchange", "in the electroneutral exchange of", "the electroneutral exchange of sodium", "electroneutral exchange of sodium ion", "exchange of sodium ion and", "of sodium ion and protons", "ion and protons orlowski", "and protons orlowski j", "protons orlowski j and", "orlowski j and grinstein s", "and grinstein s 2004", "2004 slc12 functions", "functions as na+ k+", "as na+ k+ and", "na+ k+ and cl", "k+ and cl ion", "and cl ion electroneutral", "cl ion electroneutral symporters", "ion electroneutral symporters hebert", "electroneutral symporters hebert sc", "symporters hebert sc et", "sc et al 2004", "2004 slc26 is", "slc26 is the trans epithelial", "is the trans epithelial multifunctional", "the trans epithelial multifunctional anion", "epithelial multifunctional anion e.g.", "multifunctional anion e.g. sulfate", "sulfate oxalate hco", "cl exchanger family", "exchanger family important in", "family important in cartilage", "in cartilage development production", "cartilage development production of", "development production of thyroid", "of thyroid hormone sound", "thyroid hormone sound amplification", "hormone sound amplification in", "sound amplification in the cochlea", "amplification in the cochlea etc", "the cochlea etc sindic", "cochlea etc sindic a", "etc sindic a et", "a et al 2007", "al 2007 dorwart", "2007 dorwart mr et", "mr et al 2008", "al 2008 ashmore", "ashmore j 2008 .", "j 2008 . slc34", "2008 . slc34 is an", ". slc34 is an important", "slc34 is an important type", "is an important type ii", "an important type ii na+/", "important type ii na+/ hpo4", "type ii na+/ hpo4 2", "na+/ hpo4 2 symporter", "2 symporter forster", "symporter forster ic et", "ic et al 2006", "al 2006 virkki", "2006 virkki lv et", "lv et al 2007", "2007 slc20 was", "slc20 was originally identified as", "was originally identified as a", "originally identified as a viral", "identified as a viral receptor", "a viral receptor and", "viral receptor and functions", "receptor and functions as", "and functions as a type", "functions as a type iii", "as a type iii na+/", "a type iii na+/ h2po4", "na+/ h2po4 symporter", "symporter collins jf et", "jf et al 2004", "al 2004 virkki", "2004 virkki lv et", "et al 2007 .", "al 2007 . eight", "2007 . eight slc", ". eight slc gene", "eight slc gene families", "slc gene families are involved", "gene families are involved in", "families are involved in the", "are involved in the transport", "involved in the transport of", "in the transport of amino", "the transport of amino acids", "transport of amino acids and", "of amino acids and oligopeptides." ] }, { "record_id": "GLY_000594_1_362", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "425397", "r hsa", "hsa 425397", "r hsa 425397" ] }, { "record_id": "GLY_000594_1_362", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transport of", "of vitamins", "and related", "related molecules", "transport of vitamins", "vitamins nucleosides", "nucleosides and", "and related molecules", "of vitamins nucleosides", "nucleosides and related", "transport of vitamins nucleosides", "vitamins nucleosides and", "nucleosides and related molecules", "this section", "section groups", "groups the", "the processes", "processes mediated", "mediated by", "by slc", "slc transporters", "by which", "which vitamins", "vitamins and", "and cofactors", "as well", "well as", "as nucleosides", "molecules cross", "cross lipid", "lipid bilayer", "bilayer membranes", "he et", "et al.", "al. 2009", "2009 .
the", ".
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four", "electrogenically.
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nucleotide", "glycoproteins.
nucleotide sugars", "sugars are", "are used", "used as", "as sugar", "sugar donors", "donors by", "by glycosyltransferases", "glycosyltransferases to", "to create", "create the", "the sugar", "sugar chains", "chains for", "for glycoconjugates", "glycoconjugates such", "such as", "as glycoproteins", "polysaccharides and", "and glycolipids.", "glycolipids. glycosyltransferases", "glycosyltransferases reside", "reside mainly", "mainly in", "apparatus and", "and endoplasmic", "endoplasmic reticulum", "whereas nucleotide", "nucleotide sugars", "are synthesized", "synthesized in", "the cytosol.", "cytosol. the", "the human", "human solute", "solute carrier", "carrier family", "family slc35", "slc35 encode", "encode nucleotide", "nucleotide sugar", "sugar transporters", "localised on", "on golgi", "golgi and", "and er", "er membranes", "which can", "can mediate", "the antiport", "antiport of", "sugars in", "in exchange", "exchange for", "for the", "the corresponding", "corresponding nucleoside", "nucleoside monophosphates", "eg. ump", "ump for", "for udp", "udp sugars", "handford et", "al. 2006", "2006 .
long", ".
long chain", "chain fatty", "fatty acids", "can be", "be used", "used for", "for energy", "energy sources", "sources and", "and steroid", "steroid hormone", "hormone synthesis", "synthesis and", "and regulate", "regulate many", "many cellular", "cellular processes", "processes such", "as inflammation", "blood pressure", "the clotting", "clotting process", "blood lipid", "lipid levels", "levels and", "and the", "the immune", "immune response.", "response. the", "the slc27a", "slc27a family", "family encode", "encode fatty", "fatty acid", "acid transporter", "transporter proteins", "stahl 2004", "2004 .
the", ".
the slc", "gene family", "family members", "members slco1", "slco1 slco2", "slco2 and", "and slco3", "slco3 encode", "encode organic", "organic anion", "anion transporting", "transporting polypeptides", "oatps .", ". oatps", "oatps are", "are membrane", "membrane transport", "transport proteins", "proteins that", "the sodium", "sodium independent", "independent transport", "of a", "a wide", "wide range", "range of", "of amphipathic", "amphipathic organic", "organic compounds", "compounds including", "including bile", "bile salts", "steroid conjugates", "thyroid hormones", "anionic oligopeptides", "oligopeptides and", "and numerous", "numerous drugs", "hagenbuch &", "& meier", "meier 2004", "2004 .", "this section groups", "section groups the", "groups the processes", "the processes mediated", "processes mediated by", "mediated by slc", "by slc transporters", "transporters by", "by which vitamins", "which vitamins and", "vitamins and cofactors", "cofactors as", "as well as", "well as nucleosides", "nucleosides nucleotides", "nucleotides nucleobases", "nucleobases and", "related molecules cross", "molecules cross lipid", "cross lipid bilayer", "lipid bilayer membranes", "membranes he", "he et al.", "et al. 2009", "al. 2009 .
the", "2009 .
the human", ".
the human slc5a6", "human slc5a6 encodes", "slc5a6 encodes the", "encodes the na+", "the na+ dependent", "na+ dependent multivitamin", "dependent multivitamin transporter", "multivitamin transporter smvt", "smvt prasad", "prasad et al.", "et al. 1999", "al. 1999 .", "1999 . smvt", ". smvt co", "smvt co transports", "co transports biotin", "biotin vitamin", "pantothoate vitamin", "b5 and", "and lipoic acid", "lipoic acid into", "acid into cells", "into cells with", "cells with na+", "with na+ ions", "na+ ions electrogenically.
four", "ions electrogenically.
four slc", "electrogenically.
four slc gene", "slc gene families", "gene families encode", "families encode transporters", "encode transporters that", "transporters that mediate", "that mediate the", "mediate the movement", "the movement of", "movement of nucleosides", "of nucleosides and", "nucleosides and free", "and free purine", "free purine and", "purine and pyrimidine", "and pyrimidine bases", "pyrimidine bases across", "bases across the", "across the plasma", "the plasma membrane.", "plasma membrane. these", "membrane. these transporters", "these transporters play", "transporters play key", "play key roles", "key roles in", "roles in nucleoside", "in nucleoside and", "nucleoside and nucleobase", "and nucleobase uptake", "nucleobase uptake for", "uptake for salvage", "for salvage pathways", "salvage pathways of", "pathways of nucleotide", "of nucleotide synthesis", "and in the", "in the cellular", "the cellular uptake", "cellular uptake of", "uptake of nucleoside", "of nucleoside analogues", "nucleoside analogues used", "analogues used in", "used in the", "in the treatment", "the treatment of", "treatment of cancers", "of cancers and", "cancers and viral", "and viral diseases", "diseases he", ".
the human gene", "human gene slc33a1", "gene slc33a1 encodes", "slc33a1 encodes acetyl", "encodes acetyl coa", "acetyl coa transporter", "coa transporter at1", "at1 kanamori", "kanamori et al.", "et al. 1997", "al. 1997 .", "1997 . acetyl", ". acetyl coa", "acetyl coa is", "coa is transported", "is transported to", "transported to the", "to the lumen", "the lumen of", "lumen of the", "of the golgi", "the golgi apparatus", "apparatus where", "where it serves", "it serves as", "serves as the", "as the substrate", "the substrate of", "substrate of acetyltransferases", "of acetyltransferases that", "acetyltransferases that o", "that o acetylates", "o acetylates sialyl", "acetylates sialyl residues", "sialyl residues of", "residues of gangliosides", "of gangliosides and", "gangliosides and glycoproteins.
nucleotide", "and glycoproteins.
nucleotide sugars", "glycoproteins.
nucleotide sugars are", "sugars are used", "are used as", "used as sugar", "as sugar donors", "sugar donors by", "donors by glycosyltransferases", "by glycosyltransferases to", "glycosyltransferases to create", "to create the", "create the sugar", "the sugar chains", "sugar chains for", "chains for glycoconjugates", "for glycoconjugates such", "glycoconjugates such as", "such as glycoproteins", "glycoproteins polysaccharides", "polysaccharides and glycolipids.", "and glycolipids. glycosyltransferases", "glycolipids. glycosyltransferases reside", "glycosyltransferases reside mainly", "reside mainly in", "mainly in the", "in the lumen", "golgi apparatus and", "apparatus and endoplasmic", "and endoplasmic reticulum", "reticulum er", "er whereas", "whereas nucleotide sugars", "nucleotide sugars are", "sugars are synthesized", "are synthesized in", "synthesized in the", "in the cytosol.", "the cytosol. the", "cytosol. the human", "the human solute", "human solute carrier", "solute carrier family", "carrier family slc35", "family slc35 encode", "slc35 encode nucleotide", "encode nucleotide sugar", "nucleotide sugar transporters", "transporters nsts", "localised on golgi", "on golgi and", "golgi and er", "and er membranes", "membranes which", "which can mediate", "can mediate the", "mediate the antiport", "the antiport of", "antiport of nucleotide", "of nucleotide sugars", "nucleotide sugars in", "sugars in exchange", "in exchange for", "exchange for the", "for the corresponding", "the corresponding nucleoside", "corresponding nucleoside monophosphates", "monophosphates eg.", "eg. ump for", "ump for udp", "for udp sugars", "handford et al.", "et al. 2006", "al. 2006 .
long", "2006 .
long chain", ".
long chain fatty", "chain fatty acids", "acids lcfas", "lcfas can", "can be used", "be used for", "used for energy", "for energy sources", "energy sources and", "sources and steroid", "and steroid hormone", "steroid hormone synthesis", "hormone synthesis and", "synthesis and regulate", "and regulate many", "regulate many cellular", "many cellular processes", "cellular processes such", "processes such as", "such as inflammation", "inflammation blood", "pressure the", "the clotting process", "process blood", "blood lipid levels", "lipid levels and", "levels and the", "and the immune", "the immune response.", "immune response. the", "response. the slc27a", "the slc27a family", "slc27a family encode", "family encode fatty", "encode fatty acid", "fatty acid transporter", "acid transporter proteins", "proteins fatps", "stahl 2004 .
the", "2004 .
the slc", ".
the slc gene", "slc gene family", "gene family members", "family members slco1", "members slco1 slco2", "slco1 slco2 and", "slco2 and slco3", "and slco3 encode", "slco3 encode organic", "encode organic anion", "organic anion transporting", "anion transporting polypeptides", "polypeptides oatps", "oatps . oatps", ". oatps are", "oatps are membrane", "are membrane transport", "membrane transport proteins", "transport proteins that", "proteins that mediate", "mediate the sodium", "the sodium independent", "sodium independent transport", "independent transport of", "transport of a", "of a wide", "a wide range", "wide range of", "range of amphipathic", "of amphipathic organic", "amphipathic organic compounds", "organic compounds including", "compounds including bile", "including bile salts", "salts steroid", "conjugates thyroid", "hormones anionic", "anionic oligopeptides and", "oligopeptides and numerous", "and numerous drugs", "drugs hagenbuch", "hagenbuch & meier", "& meier 2004", "meier 2004 .", "this section groups the", "section groups the processes", "groups the processes mediated", "the processes mediated by", "processes mediated by slc", "mediated by slc transporters", "slc transporters by", "transporters by which", "by which vitamins and", "which vitamins and cofactors", "and cofactors as", "cofactors as well", "as well as nucleosides", "as nucleosides nucleotides", "nucleobases and related", "and related molecules cross", "related molecules cross lipid", "molecules cross lipid bilayer", "cross lipid bilayer membranes", "bilayer membranes he", "membranes he et", "he et al. 2009", "et al. 2009 .
the", "al. 2009 .
the human", "2009 .
the human slc5a6", ".
the human slc5a6 encodes", "human slc5a6 encodes the", "slc5a6 encodes the na+", "encodes the na+ dependent", "the na+ dependent multivitamin", "na+ dependent multivitamin transporter", "dependent multivitamin transporter smvt", "transporter smvt prasad", "smvt prasad et", "prasad et al. 1999", "et al. 1999 .", "al. 1999 . smvt", "1999 . smvt co", ". smvt co transports", "smvt co transports biotin", "transports biotin vitamin", "biotin vitamin b7", "b7 d", "d pantothoate vitamin", "pantothoate vitamin b5", "vitamin b5 and", "b5 and lipoic", "and lipoic acid into", "lipoic acid into cells", "acid into cells with", "into cells with na+", "cells with na+ ions", "with na+ ions electrogenically.
four", "na+ ions electrogenically.
four slc", "ions electrogenically.
four slc gene", "electrogenically.
four slc gene families", "slc gene families encode", "gene families encode transporters", "families encode transporters that", "encode transporters that mediate", "transporters that mediate the", "that mediate the movement", "mediate the movement of", "the movement of nucleosides", "movement of nucleosides and", "of nucleosides and free", "nucleosides and free purine", "and free purine and", "free purine and pyrimidine", "purine and pyrimidine bases", "and pyrimidine bases across", "pyrimidine bases across the", "bases across the plasma", "across the plasma membrane.", "the plasma membrane. these", "plasma membrane. these transporters", "membrane. these transporters play", "these transporters play key", "transporters play key roles", "play key roles in", "key roles in nucleoside", "roles in nucleoside and", "in nucleoside and nucleobase", "nucleoside and nucleobase uptake", "and nucleobase uptake for", "nucleobase uptake for salvage", "uptake for salvage pathways", "for salvage pathways of", "salvage pathways of nucleotide", "pathways of nucleotide synthesis", "nucleotide synthesis and", "synthesis and in", "and in the cellular", "in the cellular uptake", "the cellular uptake of", "cellular uptake of nucleoside", "uptake of nucleoside analogues", "of nucleoside analogues used", "nucleoside analogues used in", "analogues used in the", "used in the treatment", "in the treatment of", "the treatment of cancers", "treatment of cancers and", "of cancers and viral", "cancers and viral diseases", "viral diseases he", "diseases he et", "2009 .
the human gene", ".
the human gene slc33a1", "human gene slc33a1 encodes", "gene slc33a1 encodes acetyl", "slc33a1 encodes acetyl coa", "encodes acetyl coa transporter", "acetyl coa transporter at1", "transporter at1 kanamori", "at1 kanamori et", "kanamori et al. 1997", "et al. 1997 .", "al. 1997 . acetyl", "1997 . acetyl coa", ". acetyl coa is", "acetyl coa is transported", "coa is transported to", "is transported to the", "transported to the lumen", "to the lumen of", "the lumen of the", "lumen of the golgi", "of the golgi apparatus", "golgi apparatus where", "apparatus where it", "where it serves as", "it serves as the", "serves as the substrate", "as the substrate of", "the substrate of acetyltransferases", "substrate of acetyltransferases that", "of acetyltransferases that o", "acetyltransferases that o acetylates", "that o acetylates sialyl", "o acetylates sialyl residues", "acetylates sialyl residues of", "sialyl residues of gangliosides", "residues of gangliosides and", "of gangliosides and glycoproteins.
nucleotide", "gangliosides and glycoproteins.
nucleotide sugars", "and glycoproteins.
nucleotide sugars are", "glycoproteins.
nucleotide sugars are used", "sugars are used as", "are used as sugar", "used as sugar donors", "as sugar donors by", "sugar donors by glycosyltransferases", "donors by glycosyltransferases to", "by glycosyltransferases to create", "glycosyltransferases to create the", "to create the sugar", "create the sugar chains", "the sugar chains for", "sugar chains for glycoconjugates", "chains for glycoconjugates such", "for glycoconjugates such as", "glycoconjugates such as glycoproteins", "as glycoproteins polysaccharides", "glycoproteins polysaccharides and", "polysaccharides and glycolipids. glycosyltransferases", "and glycolipids. glycosyltransferases reside", "glycolipids. glycosyltransferases reside mainly", "glycosyltransferases reside mainly in", "reside mainly in the", "mainly in the lumen", "in the lumen of", "the golgi apparatus and", "golgi apparatus and endoplasmic", "apparatus and endoplasmic reticulum", "endoplasmic reticulum er", "er whereas nucleotide", "whereas nucleotide sugars are", "nucleotide sugars are synthesized", "sugars are synthesized in", "are synthesized in the", "synthesized in the cytosol.", "in the cytosol. the", "the cytosol. the human", "cytosol. the human solute", "the human solute carrier", "human solute carrier family", "solute carrier family slc35", "carrier family slc35 encode", "family slc35 encode nucleotide", "slc35 encode nucleotide sugar", "encode nucleotide sugar transporters", "sugar transporters nsts", "nsts localised", "localised on golgi and", "on golgi and er", "golgi and er membranes", "er membranes which", "membranes which can", "which can mediate the", "can mediate the antiport", "mediate the antiport of", "the antiport of nucleotide", "antiport of nucleotide sugars", "of nucleotide sugars in", "nucleotide sugars in exchange", "sugars in exchange for", "in exchange for the", "exchange for the corresponding", "for the corresponding nucleoside", "the corresponding nucleoside monophosphates", "nucleoside monophosphates eg.", "monophosphates eg. ump", "eg. ump for udp", "ump for udp sugars", "sugars handford", "handford et al. 2006", "et al. 2006 .
long", "al. 2006 .
long chain", "2006 .
long chain fatty", ".
long chain fatty acids", "fatty acids lcfas", "lcfas can be", "can be used for", "be used for energy", "used for energy sources", "for energy sources and", "energy sources and steroid", "sources and steroid hormone", "and steroid hormone synthesis", "steroid hormone synthesis and", "hormone synthesis and regulate", "synthesis and regulate many", "and regulate many cellular", "regulate many cellular processes", "many cellular processes such", "cellular processes such as", "processes such as inflammation", "as inflammation blood", "inflammation blood pressure", "blood pressure the", "pressure the clotting", "clotting process blood", "process blood lipid", "blood lipid levels and", "lipid levels and the", "levels and the immune", "and the immune response.", "the immune response. the", "immune response. the slc27a", "response. the slc27a family", "the slc27a family encode", "slc27a family encode fatty", "family encode fatty acid", "encode fatty acid transporter", "fatty acid transporter proteins", "transporter proteins fatps", "fatps stahl", "stahl 2004 .
the slc", "2004 .
the slc gene", ".
the slc gene family", "slc gene family members", "gene family members slco1", "family members slco1 slco2", "members slco1 slco2 and", "slco1 slco2 and slco3", "slco2 and slco3 encode", "and slco3 encode organic", "slco3 encode organic anion", "encode organic anion transporting", "organic anion transporting polypeptides", "transporting polypeptides oatps", "polypeptides oatps .", "oatps . oatps are", ". oatps are membrane", "oatps are membrane transport", "are membrane transport proteins", "membrane transport proteins that", "transport proteins that mediate", "proteins that mediate the", "that mediate the sodium", "mediate the sodium independent", "the sodium independent transport", "sodium independent transport of", "independent transport of a", "transport of a wide", "of a wide range", "a wide range of", "wide range of amphipathic", "range of amphipathic organic", "of amphipathic organic compounds", "amphipathic organic compounds including", "organic compounds including bile", "compounds including bile salts", "bile salts steroid", "salts steroid conjugates", "steroid conjugates thyroid", "conjugates thyroid hormones", "thyroid hormones anionic", "hormones anionic oligopeptides", "anionic oligopeptides and numerous", "oligopeptides and numerous drugs", "numerous drugs hagenbuch", "drugs hagenbuch &", "hagenbuch & meier 2004", "& meier 2004 .", "this section groups the processes", "section groups the processes mediated", "groups the processes mediated by", "the processes mediated by slc", "processes mediated by slc transporters", "by slc transporters by", "slc transporters by which", "transporters by which vitamins", "by which vitamins and cofactors", "vitamins and cofactors as", "and cofactors as well", "cofactors as well as", "well as nucleosides nucleotides", "nucleosides nucleotides nucleobases", "nucleotides nucleobases and", "nucleobases and related molecules", "and related molecules cross lipid", "related molecules cross lipid bilayer", "molecules cross lipid bilayer membranes", "lipid bilayer membranes he", "bilayer membranes he et", "membranes he et al.", "he et al. 2009 .
the", "et al. 2009 .
the human", "al. 2009 .
the human slc5a6", "2009 .
the human slc5a6 encodes", ".
the human slc5a6 encodes the", "human slc5a6 encodes the na+", "slc5a6 encodes the na+ dependent", "encodes the na+ dependent multivitamin", "the na+ dependent multivitamin transporter", "na+ dependent multivitamin transporter smvt", "multivitamin transporter smvt prasad", "transporter smvt prasad et", "smvt prasad et al.", "prasad et al. 1999 .", "et al. 1999 . smvt", "al. 1999 . smvt co", "1999 . smvt co transports", ". smvt co transports biotin", "co transports biotin vitamin", "transports biotin vitamin b7", "vitamin b7 d", "b7 d pantothoate", "d pantothoate vitamin b5", "vitamin b5 and lipoic", "b5 and lipoic acid", "and lipoic acid into cells", "lipoic acid into cells with", "acid into cells with na+", "into cells with na+ ions", "cells with na+ ions electrogenically.
four", "with na+ ions electrogenically.
four slc", "na+ ions electrogenically.
four slc gene", "ions electrogenically.
four slc gene families", "electrogenically.
four slc gene families encode", "slc gene families encode transporters", "gene families encode transporters that", "families encode transporters that mediate", "encode transporters that mediate the", "transporters that mediate the movement", "that mediate the movement of", "mediate the movement of nucleosides", "the movement of nucleosides and", "movement of nucleosides and free", "of nucleosides and free purine", "nucleosides and free purine and", "and free purine and pyrimidine", "free purine and pyrimidine bases", "purine and pyrimidine bases across", "and pyrimidine bases across the", "pyrimidine bases across the plasma", "bases across the plasma membrane.", "across the plasma membrane. these", "the plasma membrane. these transporters", "plasma membrane. these transporters play", "membrane. these transporters play key", "these transporters play key roles", "transporters play key roles in", "play key roles in nucleoside", "key roles in nucleoside and", "roles in nucleoside and nucleobase", "in nucleoside and nucleobase uptake", "nucleoside and nucleobase uptake for", "and nucleobase uptake for salvage", "nucleobase uptake for salvage pathways", "uptake for salvage pathways of", "for salvage pathways of nucleotide", "salvage pathways of nucleotide synthesis", "of nucleotide synthesis and", "nucleotide synthesis and in", "synthesis and in the", "and in the cellular uptake", "in the cellular uptake of", "the cellular uptake of nucleoside", "cellular uptake of nucleoside analogues", "uptake of nucleoside analogues used", "of nucleoside analogues used in", "nucleoside analogues used in the", "analogues used in the treatment", "used in the treatment of", "in the treatment of cancers", "the treatment of cancers and", "treatment of cancers and viral", "of cancers and viral diseases", "and viral diseases he", "viral diseases he et", "diseases he et al.", "al. 2009 .
the human gene", "2009 .
the human gene slc33a1", ".
the human gene slc33a1 encodes", "human gene slc33a1 encodes acetyl", "gene slc33a1 encodes acetyl coa", "slc33a1 encodes acetyl coa transporter", "encodes acetyl coa transporter at1", "coa transporter at1 kanamori", "transporter at1 kanamori et", "at1 kanamori et al.", "kanamori et al. 1997 .", "et al. 1997 . acetyl", "al. 1997 . acetyl coa", "1997 . acetyl coa is", ". acetyl coa is transported", "acetyl coa is transported to", "coa is transported to the", "is transported to the lumen", "transported to the lumen of", "to the lumen of the", "the lumen of the golgi", "lumen of the golgi apparatus", "the golgi apparatus where", "golgi apparatus where it", "apparatus where it serves", "where it serves as the", "it serves as the substrate", "serves as the substrate of", "as the substrate of acetyltransferases", "the substrate of acetyltransferases that", "substrate of acetyltransferases that o", "of acetyltransferases that o acetylates", "acetyltransferases that o acetylates sialyl", "that o acetylates sialyl residues", "o acetylates sialyl residues of", "acetylates sialyl residues of gangliosides", "sialyl residues of gangliosides and", "residues of gangliosides and glycoproteins.
nucleotide", "of gangliosides and glycoproteins.
nucleotide sugars", "gangliosides and glycoproteins.
nucleotide sugars are", "and glycoproteins.
nucleotide sugars are used", "glycoproteins.
nucleotide sugars are used as", "sugars are used as sugar", "are used as sugar donors", "used as sugar donors by", "as sugar donors by glycosyltransferases", "sugar donors by glycosyltransferases to", "donors by glycosyltransferases to create", "by glycosyltransferases to create the", "glycosyltransferases to create the sugar", "to create the sugar chains", "create the sugar chains for", "the sugar chains for glycoconjugates", "sugar chains for glycoconjugates such", "chains for glycoconjugates such as", "for glycoconjugates such as glycoproteins", "such as glycoproteins polysaccharides", "as glycoproteins polysaccharides and", "glycoproteins polysaccharides and glycolipids.", "polysaccharides and glycolipids. glycosyltransferases reside", "and glycolipids. glycosyltransferases reside mainly", "glycolipids. glycosyltransferases reside mainly in", "glycosyltransferases reside mainly in the", "reside mainly in the lumen", "mainly in the lumen of", "in the lumen of the", "of the golgi apparatus and", "the golgi apparatus and endoplasmic", "golgi apparatus and endoplasmic reticulum", "and endoplasmic reticulum er", "reticulum er whereas", "er whereas nucleotide sugars", "whereas nucleotide sugars are synthesized", "nucleotide sugars are synthesized in", "sugars are synthesized in the", "are synthesized in the cytosol.", "synthesized in the cytosol. the", "in the cytosol. the human", "the cytosol. the human solute", "cytosol. the human solute carrier", "the human solute carrier family", "human solute carrier family slc35", "solute carrier family slc35 encode", "carrier family slc35 encode nucleotide", "family slc35 encode nucleotide sugar", "slc35 encode nucleotide sugar transporters", "nucleotide sugar transporters nsts", "nsts localised on", "localised on golgi and er", "on golgi and er membranes", "and er membranes which", "er membranes which can", "membranes which can mediate", "which can mediate the antiport", "can mediate the antiport of", "mediate the antiport of nucleotide", "the antiport of nucleotide sugars", "antiport of nucleotide sugars in", "of nucleotide sugars in exchange", "nucleotide sugars in exchange for", "sugars in exchange for the", "in exchange for the corresponding", "exchange for the corresponding nucleoside", "for the corresponding nucleoside monophosphates", "corresponding nucleoside monophosphates eg.", "nucleoside monophosphates eg. ump", "monophosphates eg. ump for", "eg. ump for udp sugars", "udp sugars handford", "sugars handford et", "handford et al. 2006 .
long", "et al. 2006 .
long chain", "al. 2006 .
long chain fatty", "2006 .
long chain fatty acids", "chain fatty acids lcfas", "acids lcfas can", "lcfas can be used", "can be used for energy", "be used for energy sources", "used for energy sources and", "for energy sources and steroid", "energy sources and steroid hormone", "sources and steroid hormone synthesis", "and steroid hormone synthesis and", "steroid hormone synthesis and regulate", "hormone synthesis and regulate many", "synthesis and regulate many cellular", "and regulate many cellular processes", "regulate many cellular processes such", "many cellular processes such as", "cellular processes such as inflammation", "such as inflammation blood", "as inflammation blood pressure", "blood pressure the clotting", "pressure the clotting process", "the clotting process blood", "clotting process blood lipid", "process blood lipid levels", "blood lipid levels and the", "lipid levels and the immune", "levels and the immune response.", "and the immune response. the", "the immune response. the slc27a", "immune response. the slc27a family", "response. the slc27a family encode", "the slc27a family encode fatty", "slc27a family encode fatty acid", "family encode fatty acid transporter", "encode fatty acid transporter proteins", "acid transporter proteins fatps", "fatps stahl 2004", "stahl 2004 .
the slc gene", "2004 .
the slc gene family", ".
the slc gene family members", "slc gene family members slco1", "gene family members slco1 slco2", "family members slco1 slco2 and", "members slco1 slco2 and slco3", "slco1 slco2 and slco3 encode", "slco2 and slco3 encode organic", "and slco3 encode organic anion", "slco3 encode organic anion transporting", "encode organic anion transporting polypeptides", "anion transporting polypeptides oatps", "transporting polypeptides oatps .", "polypeptides oatps . oatps", "oatps . oatps are membrane", ". oatps are membrane transport", "oatps are membrane transport proteins", "are membrane transport proteins that", "membrane transport proteins that mediate", "transport proteins that mediate the", "proteins that mediate the sodium", "that mediate the sodium independent", "mediate the sodium independent transport", "the sodium independent transport of", "sodium independent transport of a", "independent transport of a wide", "transport of a wide range", "of a wide range of", "a wide range of amphipathic", "wide range of amphipathic organic", "range of amphipathic organic compounds", "of amphipathic organic compounds including", "amphipathic organic compounds including bile", "organic compounds including bile salts", "including bile salts steroid", "bile salts steroid conjugates", "steroid conjugates thyroid hormones", "thyroid hormones anionic oligopeptides", "hormones anionic oligopeptides and", "anionic oligopeptides and numerous drugs", "and numerous drugs hagenbuch", "numerous drugs hagenbuch &", "drugs hagenbuch & meier", "hagenbuch & meier 2004 ." ] }, { "record_id": "GLY_000594_1_363", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "425410", "r hsa", "hsa 425410", "r hsa 425410" ] }, { "record_id": "GLY_000594_1_363", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "metal ion", "ion slc", "slc transporters", "metal ion slc", "ion slc transporters", "metal ion slc transporters", "six slc", "slc gene", "gene families", "families encode", "encode proteins", "proteins which", "which mediate", "mediate transport", "transport of", "of metals.", "metals. the", "the families", "families are", "are slc11", "slc40 and", "and slc41", "he l", "l et", "et al", "bressler jp", "jp et", "2007 .", "six slc gene", "slc gene families", "gene families encode", "families encode proteins", "encode proteins which", "proteins which mediate", "which mediate transport", "mediate transport of", "transport of metals.", "of metals. the", "metals. the families", "the families are", "families are slc11", "slc11 slc30", "slc30 slc31", "slc31 slc39", "slc39 slc40", "slc40 and slc41", "slc41 he", "he l et", "l et al", "al 2009", "2009 bressler", "bressler jp et", "jp et al", "al 2007", "six slc gene families", "slc gene families encode", "gene families encode proteins", "families encode proteins which", "encode proteins which mediate", "proteins which mediate transport", "which mediate transport of", "mediate transport of metals.", "transport of metals. the", "of metals. the families", "metals. the families are", "the families are slc11", "are slc11 slc30", "slc39 slc40 and", "and slc41 he", "slc41 he l", "he l et al", "et al 2009", "2009 bressler jp", "bressler jp et al", "et al 2007", "al 2007 .", "six slc gene families encode", "slc gene families encode proteins", "gene families encode proteins which", "families encode proteins which mediate", "encode proteins which mediate transport", "proteins which mediate transport of", "which mediate transport of metals.", "mediate transport of metals. the", "transport of metals. the families", "of metals. the families are", "metals. the families are slc11", "families are slc11 slc30", "slc11 slc30 slc31", "slc30 slc31 slc39", "slc31 slc39 slc40", "slc39 slc40 and slc41", "slc40 and slc41 he", "and slc41 he l", "slc41 he l et", "l et al 2009", "al 2009 bressler", "2009 bressler jp et", "jp et al 2007", "et al 2007 ." ] }, { "record_id": "GLY_000594_1_364", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "427413", "r hsa", "hsa 427413", "r hsa 427413" ] }, { "record_id": "GLY_000594_1_364", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "norc negatively", "negatively regulates", "regulates rrna", "rrna expression", "norc negatively regulates", "negatively regulates rrna", "regulates rrna expression", "norc negatively regulates rrna", "negatively regulates rrna expression", "norc negatively regulates rrna expression", "the nucleolar", "nucleolar remodeling", "remodeling complex", "comprising tip5", "and the", "the chromatin", "chromatin remodeller", "remodeller snf2h", "silences rrna", "rrna gene", "reviewed in", "in santoro", "santoro and", "and grummt", "grummt 2001", "grummt 2007", "preuss and", "and pikaard", "pikaard 2007", "birch and", "and zommerdijk", "zommerdijk 2008", "mcstay and", "grummt 2008", "grummt and", "and langst", "langst 2013", "2013 .", ". the", "the tam", "tam domain", "domain of", "of tip5", "binds promoter", "promoter associated", "associated rna", "transcribed from", "from the", "the intergenic", "intergenic spacer", "spacer region", "region of", "of rdna.", "rdna. the", "the prna", "prna bound", "bound by", "by tip5", "tip5 is", "is required", "required to", "to direct", "direct the", "the complex", "complex to", "to the", "the main", "main promoter", "promoter of", "of the", "the rrna", "gene possibly", "possibly by", "by triple", "triple helix", "helix formation", "formation between", "between prna", "prna and", "the rdna.", "the phd", "phd domain", "tip5 binds", "binds histone", "histone h4", "h4 acetylated", "acetylated at", "at lysine", "lysine 16.", "16. transcription", "transcription termination", "termination factor", "factor i", "ttf i", "binds to", "to a", "a promoter", "promoter proximal", "proximal terminator", "t0 site", "in the", "the rdna", "rdna and", "and interacts", "interacts with", "with the", "the tip5", "tip5 subunit", "subunit of", "of norc.", "norc. norc", "norc also", "also interacts", "the sin3", "sin3 hdac", "hdac complex", "and dnmt3b.", "dnmt3b. dnmt3b", "dnmt3b interacts", "with a", "a triple", "helix formed", "formed by", "by prna", "rdna. hdac1", "and dnmt3b", "dnmt3b have", "have been", "been shown", "shown to", "to be", "be required", "required for", "for proper", "proper dna", "dna methylation", "methylation of", "of silenced", "silenced rrna", "gene copies", "although the", "the catalytic", "catalytic activity", "activity of", "of dnmt3b", "dnmt3b was", "was not", "not required.", "the nucleolar remodeling", "nucleolar remodeling complex", "complex norc", "norc comprising", "tip5 baz2a", "baz2a and", "and the chromatin", "the chromatin remodeller", "chromatin remodeller snf2h", "snf2h smarca5", "smarca5 silences", "silences rrna gene", "gene reviewed", "reviewed in santoro", "in santoro and", "santoro and grummt", "and grummt 2001", "2001 grummt", "2007 preuss", "preuss and pikaard", "and pikaard 2007", "2007 birch", "birch and zommerdijk", "and zommerdijk 2008", "2008 mcstay", "mcstay and grummt", "and grummt 2008", "2008 grummt", "grummt and langst", "and langst 2013", "langst 2013 .", "2013 . the", ". the tam", "the tam domain", "tam domain of", "domain of tip5", "baz2a binds", "binds promoter associated", "promoter associated rna", "rna prna", "prna transcribed", "transcribed from the", "from the intergenic", "the intergenic spacer", "intergenic spacer region", "spacer region of", "region of rdna.", "of rdna. the", "rdna. the prna", "the prna bound", "prna bound by", "bound by tip5", "by tip5 is", "tip5 is required", "is required to", "required to direct", "to direct the", "direct the complex", "the complex to", "complex to the", "to the main", "the main promoter", "main promoter of", "promoter of the", "of the rrna", "the rrna gene", "rrna gene possibly", "gene possibly by", "possibly by triple", "by triple helix", "triple helix formation", "helix formation between", "formation between prna", "between prna and", "prna and the", "and the rdna.", "the rdna. the", "rdna. the phd", "the phd domain", "phd domain of", "of tip5 binds", "tip5 binds histone", "binds histone h4", "histone h4 acetylated", "h4 acetylated at", "acetylated at lysine", "at lysine 16.", "lysine 16. transcription", "16. transcription termination", "transcription termination factor", "termination factor i", "i ttf", "i binds", "binds to a", "to a promoter", "a promoter proximal", "promoter proximal terminator", "terminator t0", "site in", "in the rdna", "the rdna and", "rdna and interacts", "and interacts with", "interacts with the", "with the tip5", "the tip5 subunit", "tip5 subunit of", "subunit of norc.", "of norc. norc", "norc. norc also", "norc also interacts", "also interacts with", "with the sin3", "the sin3 hdac", "sin3 hdac complex", "complex hdac1", "hdac1 hdac2", "hdac2 dnmt1", "dnmt1 and", "and dnmt3b. dnmt3b", "dnmt3b. dnmt3b interacts", "dnmt3b interacts with", "interacts with a", "with a triple", "a triple helix", "triple helix formed", "helix formed by", "formed by prna", "by prna and", "the rdna. hdac1", "hdac1 dnmt1", "and dnmt3b have", "dnmt3b have been", "have been shown", "been shown to", "shown to be", "to be required", "be required for", "required for proper", "for proper dna", "proper dna methylation", "dna methylation of", "methylation of silenced", "of silenced rrna", "silenced rrna gene", "rrna gene copies", "copies although", "although the catalytic", "the catalytic activity", "catalytic activity of", "activity of dnmt3b", "of dnmt3b was", "dnmt3b was not", "was not required.", "the nucleolar remodeling complex", "remodeling complex norc", "norc comprising tip5", "comprising tip5 baz2a", "baz2a and the", "and the chromatin remodeller", "the chromatin remodeller snf2h", "remodeller snf2h smarca5", "smarca5 silences rrna", "rrna gene reviewed", "gene reviewed in", "reviewed in santoro and", "in santoro and grummt", "santoro and grummt 2001", "grummt 2001 grummt", "2001 grummt 2007", "grummt 2007 preuss", "2007 preuss and", "preuss and pikaard 2007", "pikaard 2007 birch", "2007 birch and", "birch and zommerdijk 2008", "zommerdijk 2008 mcstay", "2008 mcstay and", "mcstay and grummt 2008", "grummt 2008 grummt", "2008 grummt and", "grummt and langst 2013", "and langst 2013 .", "langst 2013 . the", "2013 . the tam", ". the tam domain", "the tam domain of", "tam domain of tip5", "of tip5 baz2a", "baz2a binds promoter", "binds promoter associated rna", "associated rna prna", "prna transcribed from", "transcribed from the intergenic", "from the intergenic spacer", "the intergenic spacer region", "intergenic spacer region of", "spacer region of rdna.", "region of rdna. the", "of rdna. the prna", "rdna. the prna bound", "the prna bound by", "prna bound by tip5", "bound by tip5 is", "by tip5 is required", "tip5 is required to", "is required to direct", "required to direct the", "to direct the complex", "direct the complex to", "the complex to the", "complex to the main", "to the main promoter", "the main promoter of", "main promoter of the", "promoter of the rrna", "of the rrna gene", "the rrna gene possibly", "rrna gene possibly by", "gene possibly by triple", "possibly by triple helix", "by triple helix formation", "triple helix formation between", "helix formation between prna", "formation between prna and", "between prna and the", "prna and the rdna.", "and the rdna. the", "the rdna. the phd", "rdna. the phd domain", "the phd domain of", "phd domain of tip5", "domain of tip5 binds", "of tip5 binds histone", "tip5 binds histone h4", "binds histone h4 acetylated", "histone h4 acetylated at", "h4 acetylated at lysine", "acetylated at lysine 16.", "at lysine 16. transcription", "lysine 16. transcription termination", "16. transcription termination factor", "transcription termination factor i", "factor i ttf", "i ttf i", "ttf i binds", "i binds to", "binds to a promoter", "to a promoter proximal", "a promoter proximal terminator", "proximal terminator t0", "terminator t0 site", "t0 site in", "site in the", "in the rdna and", "the rdna and interacts", "rdna and interacts with", "and interacts with the", "interacts with the tip5", "with the tip5 subunit", "the tip5 subunit of", "tip5 subunit of norc.", "subunit of norc. norc", "of norc. norc also", "norc. norc also interacts", "norc also interacts with", "also interacts with the", "interacts with the sin3", "with the sin3 hdac", "the sin3 hdac complex", "hdac complex hdac1", "dnmt1 and dnmt3b.", "and dnmt3b. dnmt3b interacts", "dnmt3b. dnmt3b interacts with", "dnmt3b interacts with a", "interacts with a triple", "with a triple helix", "a triple helix formed", "triple helix formed by", "helix formed by prna", "formed by prna and", "by prna and the", "and the rdna. hdac1", "rdna. hdac1 dnmt1", "dnmt1 and dnmt3b", "and dnmt3b have been", "dnmt3b have been shown", "have been shown to", "been shown to be", "shown to be required", "to be required for", "be required for proper", "required for proper dna", "for proper dna methylation", "proper dna methylation of", "dna methylation of silenced", "methylation of silenced rrna", "of silenced rrna gene", "silenced rrna gene copies", "gene copies although", "copies although the", "although the catalytic activity", "the catalytic activity of", "catalytic activity of dnmt3b", "activity of dnmt3b was", "of dnmt3b was not", "dnmt3b was not required.", "nucleolar remodeling complex norc", "complex norc comprising", "tip5 baz2a and", "baz2a and the chromatin", "and the chromatin remodeller snf2h", "chromatin remodeller snf2h smarca5", "snf2h smarca5 silences", "smarca5 silences rrna gene", "silences rrna gene reviewed", "rrna gene reviewed in", "gene reviewed in santoro", "reviewed in santoro and grummt", "in santoro and grummt 2001", "and grummt 2001 grummt", "grummt 2001 grummt 2007", "grummt 2007 preuss and", "2007 preuss and pikaard", "and pikaard 2007 birch", "pikaard 2007 birch and", "2007 birch and zommerdijk", "and zommerdijk 2008 mcstay", "zommerdijk 2008 mcstay and", "2008 mcstay and grummt", "and grummt 2008 grummt", "grummt 2008 grummt and", "2008 grummt and langst", "grummt and langst 2013 .", "and langst 2013 . the", "langst 2013 . the tam", "2013 . the tam domain", ". the tam domain of", "the tam domain of tip5", "domain of tip5 baz2a", "tip5 baz2a binds", "baz2a binds promoter associated", "promoter associated rna prna", "rna prna transcribed", "prna transcribed from the", "transcribed from the intergenic spacer", "from the intergenic spacer region", "the intergenic spacer region of", "intergenic spacer region of rdna.", "spacer region of rdna. the", "region of rdna. the prna", "of rdna. the prna bound", "rdna. the prna bound by", "the prna bound by tip5", "prna bound by tip5 is", "bound by tip5 is required", "by tip5 is required to", "tip5 is required to direct", "is required to direct the", "required to direct the complex", "to direct the complex to", "direct the complex to the", "the complex to the main", "complex to the main promoter", "to the main promoter of", "the main promoter of the", "main promoter of the rrna", "promoter of the rrna gene", "of the rrna gene possibly", "the rrna gene possibly by", "rrna gene possibly by triple", "gene possibly by triple helix", "possibly by triple helix formation", "by triple helix formation between", "triple helix formation between prna", "helix formation between prna and", "formation between prna and the", "between prna and the rdna.", "prna and the rdna. the", "and the rdna. the phd", "the rdna. the phd domain", "rdna. the phd domain of", "the phd domain of tip5", "phd domain of tip5 binds", "domain of tip5 binds histone", "of tip5 binds histone h4", "tip5 binds histone h4 acetylated", "binds histone h4 acetylated at", "histone h4 acetylated at lysine", "h4 acetylated at lysine 16.", "acetylated at lysine 16. transcription", "at lysine 16. transcription termination", "lysine 16. transcription termination factor", "16. transcription termination factor i", "termination factor i ttf", "factor i ttf i", "ttf i binds to", "i binds to a", "binds to a promoter proximal", "to a promoter proximal terminator", "promoter proximal terminator t0", "proximal terminator t0 site", "t0 site in the", "site in the rdna", "in the rdna and interacts", "the rdna and interacts with", "rdna and interacts with the", "and interacts with the tip5", "interacts with the tip5 subunit", "with the tip5 subunit of", "the tip5 subunit of norc.", "tip5 subunit of norc. norc", "subunit of norc. norc also", "of norc. norc also interacts", "norc. norc also interacts with", "norc also interacts with the", "also interacts with the sin3", "interacts with the sin3 hdac", "with the sin3 hdac complex", "sin3 hdac complex hdac1", "complex hdac1 hdac2", "hdac1 hdac2 dnmt1", "hdac2 dnmt1 and", "dnmt1 and dnmt3b. dnmt3b", "and dnmt3b. dnmt3b interacts with", "dnmt3b. dnmt3b interacts with a", "dnmt3b interacts with a triple", "interacts with a triple helix", "with a triple helix formed", "a triple helix formed by", "triple helix formed by prna", "helix formed by prna and", "formed by prna and the", "by prna and the rdna.", "prna and the rdna. hdac1", "the rdna. hdac1 dnmt1", "hdac1 dnmt1 and", "dnmt1 and dnmt3b have", "and dnmt3b have been shown", "dnmt3b have been shown to", "have been shown to be", "been shown to be required", "shown to be required for", "to be required for proper", "be required for proper dna", "required for proper dna methylation", "for proper dna methylation of", "proper dna methylation of silenced", "dna methylation of silenced rrna", "methylation of silenced rrna gene", "of silenced rrna gene copies", "rrna gene copies although", "gene copies although the", "copies although the catalytic", "although the catalytic activity of", "the catalytic activity of dnmt3b", "catalytic activity of dnmt3b was", "activity of dnmt3b was not", "of dnmt3b was not required." ] }, { "record_id": "GLY_000594_1_365", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "428359", "r hsa", "hsa 428359", "r hsa 428359" ] }, { "record_id": "GLY_000594_1_365", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "insulin like", "like growth", "growth factor", "factor 2", "2 mrna", "mrna binding", "binding proteins", "bind rna", "insulin like growth", "like growth factor", "growth factor 2", "factor 2 mrna", "2 mrna binding", "mrna binding proteins", "proteins igf2bps/imps/vickzs", "igf2bps/imps/vickzs bind", "insulin like growth factor", "like growth factor 2", "growth factor 2 mrna", "factor 2 mrna binding", "2 mrna binding proteins", "binding proteins igf2bps/imps/vickzs", "igf2bps/imps/vickzs bind rna", "insulin like growth factor 2", "like growth factor 2 mrna", "growth factor 2 mrna 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localization. igf2bp1", "igf2bp1 igf2bp2", "igf2bp2 and", "and igf2bp3 bind", "igf2bp3 bind about", "bind about 8400", "about 8400 protein", "8400 protein coding", "protein coding transcripts.", "coding transcripts. the", "transcripts. the target", "the target rnas", "target rnas contain", "rnas contain the", "contain the sequence", "the sequence motif", "sequence motif cauh", "cauh where", "where h is", "h is a", "a u", "u or", "or c", "c and", "and binding of", "binding of igfbps", "of igfbps increases", "igfbps increases the", "increases the stability", "the stability of", "stability of the", "of the target", "the target rnas.", "binding proteins igf2bps", "igf2bps bind specific", "bind specific sets of", "specific sets of rna", "sets of rna and", "of rna and regulate", "rna and regulate their", "and regulate their translation", "their translation stability", "stability and subcellular", "and subcellular localization. igf2bp1", "localization. igf2bp1 igf2bp2", "igf2bp2 and igf2bp3", "and igf2bp3 bind about", "igf2bp3 bind about 8400", "bind about 8400 protein", "about 8400 protein coding", "8400 protein coding transcripts.", "protein coding transcripts. the", "coding transcripts. the target", "transcripts. the target rnas", "the target rnas contain", "target rnas contain the", "rnas contain the sequence", "contain the sequence motif", "the sequence motif cauh", "motif cauh where", "cauh where h", "where h is a", "is a u", "c and binding", "and binding of igfbps", "binding of igfbps increases", "of igfbps increases the", "igfbps increases the stability", "increases the stability of", "the stability of the", "stability of the target", "of the target rnas.", "mrna binding proteins igf2bps", "proteins igf2bps bind", "igf2bps bind specific sets", "bind specific sets of rna", "specific sets of rna and", "sets of rna and regulate", "of rna and regulate their", "rna and regulate their translation", "regulate their translation stability", "translation stability and", "stability and subcellular localization.", "subcellular localization. igf2bp1 igf2bp2", "igf2bp1 igf2bp2 and", "igf2bp2 and igf2bp3 bind", "and igf2bp3 bind about 8400", "igf2bp3 bind about 8400 protein", "bind about 8400 protein coding", "about 8400 protein coding transcripts.", "8400 protein coding transcripts. the", "protein coding transcripts. the target", "coding transcripts. the target rnas", "transcripts. the target rnas contain", "the target rnas contain the", "target rnas contain the sequence", "rnas contain the sequence motif", "contain the sequence motif cauh", "sequence motif cauh where", "motif cauh where h", "cauh where h is", "h is a u", "a u or", "u or c", "or c and", "c and binding of", "and binding of igfbps increases", "binding of igfbps increases the", "of igfbps increases the stability", "igfbps increases the stability of", "increases the stability of the", "the stability of the target", "stability of the target rnas." ] }, { "record_id": "GLY_000594_1_366", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "428930", "r hsa", "hsa 428930", "r hsa 428930" ] }, { "record_id": "GLY_000594_1_366", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "thromboxane signalling", "signalling through", "through tp", "tp receptor", "thromboxane signalling through", "signalling through tp", "through tp receptor", "thromboxane signalling through tp", "signalling through tp receptor", "thromboxane signalling through tp receptor", "binds to", "to the", "the thromboxane", "thromboxane receptor", "tp .", ". there", "there are", "are 2", "2 splice", "splice variant", "variant forms", "forms of", "of tp", "differing in", "in their", "their cytoplasmic", "cytoplasmic carboxyl", "carboxyl terminal", "terminal tails.", "tails. tp", "tp beta", "beta was", "was first", "first identified", "identified in", "in endothelial", "endothelial cells.", "cells. tp", "tp alpha", "alpha 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are 2", "there are 2 splice", "are 2 splice variant", "2 splice variant forms", "splice variant forms of", "variant forms of tp", "of tp differing", "tp differing in", "differing in their cytoplasmic", "in their cytoplasmic carboxyl", "their cytoplasmic carboxyl terminal", "cytoplasmic carboxyl terminal tails.", "carboxyl terminal tails. tp", "terminal tails. tp beta", "tails. tp beta was", "tp beta was first", "beta was first identified", "was first identified in", "first identified in endothelial", "identified in endothelial cells.", "in endothelial cells. tp", "endothelial cells. tp alpha", "cells. tp alpha was", "tp alpha was identified", "alpha was identified in", "was identified in platelets", "identified in platelets and", "in platelets and placenta.", "platelets and placenta. the", "and placenta. the major", "placenta. the major signalling", "the major signalling route", "major signalling route for", "signalling route for tp", "route for tp is", "for tp is gq", "tp is gq 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cytoplasmic carboxyl terminal", "their cytoplasmic carboxyl terminal tails.", "cytoplasmic carboxyl terminal tails. tp", "carboxyl terminal tails. tp beta", "terminal tails. tp beta was", "tails. tp beta was first", "tp beta was first identified", "beta was first identified in", "was first identified in endothelial", "first identified in endothelial cells.", "identified in endothelial cells. tp", "in endothelial cells. tp alpha", "endothelial cells. tp alpha was", "cells. tp alpha was identified", "tp alpha was identified in", "alpha was identified in platelets", "was identified in platelets and", "identified in platelets and placenta.", "in platelets and placenta. the", "platelets and placenta. the major", "and placenta. the major signalling", "placenta. the major signalling route", "the major signalling route for", "major signalling route for tp", "signalling route for tp is", "route for tp is gq", "for tp is gq mediated", "tp is gq mediated stimulation", "is gq mediated stimulation of", "gq mediated stimulation of plc", "mediated stimulation of plc and", "stimulation of plc and consequent", "of plc and consequent increase", "plc and consequent increase in", "and consequent increase in cellular", "consequent increase in cellular calcium.", "increase in cellular calcium. tp", "in cellular calcium. tp also", "cellular calcium. tp also couples", "calcium. tp also couples to", "tp also couples to g13", "couples to g13 leading", "to g13 leading to", "g13 leading to stimulation", "leading to stimulation of rho", "to stimulation of rho and", "stimulation of rho and rac." ] }, { "record_id": "GLY_000594_1_367", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "429947", "r hsa", "hsa 429947", "r hsa 429947" ] }, { "record_id": "GLY_000594_1_367", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "deadenylation of", "of mrna", "deadenylation of mrna", "mrna proceeds", "proceeds in", "in two", "two steps.", "steps. according", "according to", "to current", "current models", "in the", "the first", "first step", "step the", "the poly", "poly a", "tail is", "is shortened", "shortened from", "from about", "about 200", "200 adenosine", "adenosine residues", "residues to", "to about", "about 80", "80 residues", "residues by", "by the", "the pan2", "pan2 pan3", "pan3 complex.", "complex. in", "the second", "second step", "is further", "further shortened", "shortened to", "to 10", "10 15", "15 residues", "by either", "either the", "the ccr4", "ccr4 not", "not complex", "complex or", "or by", "the parn", "parn exoribonuclease.", "exoribonuclease. how", "how a", "a particular", "particular mrna", "mrna is", "is targeted", "targeted to", "to ccr4", "not or", "or parn", "parn is", "is unknown.
a", "unknown.
a number", "number of", "of other", "other deadenylase", "deadenylase enzymes", "enzymes can", "can be", "be identified", "identified in", "in genomic", "genomic searches.", "one particularly", "particularly interesting", "interesting one", "one is", "is nocturin", "a protein", "protein that", "that is", "is related", "related to", "to the", "the ccr", "ccr 1", "1 deadenylase", "deadenylase and", "and plays", "plays a", "a role", "role in", "in circadian", "circadian rhythms.
there", "rhythms.
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a", "is unknown.
a number", "unknown.
a number of", "number of other", "of other deadenylase", "other deadenylase enzymes", "deadenylase enzymes can", "enzymes can be", "can be identified", "be identified in", "identified in genomic", "in genomic searches.", "searches. one", "one particularly interesting", "particularly interesting one", "interesting one is", "one is nocturin", "nocturin a", "a protein that", "protein that is", "that is related", "is related to", "related to the", "to the ccr", "the ccr 1", "ccr 1 deadenylase", "1 deadenylase and", "deadenylase and plays", "and plays a", "plays a role", "a role in", "role in circadian", "in circadian rhythms.
there", "circadian rhythms.
there is", "rhythms.
there is also", "is also evidence", "also evidence for", "evidence for networking", "for networking between", "networking between deadenylation", "between deadenylation and", "deadenylation and other", "and other aspects", "other aspects of", "aspects of gene", "of gene expression.", "gene expression. ccr4", "expression. ccr4 not", "not for", "example is", "is known to", "known to be", "to be a", "be a transcription", "a transcription factor.", "transcription factor. parn", "factor. parn is", "parn is part", "is part of", "part of a", "of a complex", "a complex that", "complex that regulates", "that regulates poly", "regulates poly a", "tail length and", "length and hence", "and hence translation", "hence translation in", "translation in developing", "in developing oocytes.", "deadenylation of mrna proceeds", "of mrna proceeds in", "mrna proceeds in two", "proceeds in two steps.", "in two steps. according", "two steps. according to", "steps. according to current", "according to current models", "current models in", "models in the", "in the first step", "the first step the", "first step the poly", "step the poly a", "poly a tail", "a tail is", "tail is shortened from", "is shortened from about", "shortened from about 200", "from about 200 adenosine", "about 200 adenosine residues", "200 adenosine residues to", "adenosine residues to about", "residues to about 80", "to about 80 residues", "about 80 residues by", "80 residues by the", "residues by the pan2", "by the pan2 pan3", "the pan2 pan3 complex.", "pan2 pan3 complex. in", "pan3 complex. in the", "complex. in the second", "in the second step", "the second step the", "second step the poly", "tail is further shortened", "is further shortened to", "further shortened to 10", "shortened to 10 15", "to 10 15 residues", "10 15 residues by", "15 residues by either", "residues by either the", "by either the ccr4", "either the ccr4 not", "the ccr4 not complex", "ccr4 not complex or", "not complex or by", "complex or by the", "or by the parn", "by the parn exoribonuclease.", "the parn exoribonuclease. how", "parn exoribonuclease. how a", "exoribonuclease. how a particular", "how a particular mrna", "a particular mrna is", "particular mrna is targeted", "mrna is targeted to", "is targeted to ccr4", "targeted to ccr4 not", "to ccr4 not or", "ccr4 not or parn", "not or parn is", "or parn is unknown.
a", "parn is unknown.
a number", "is unknown.
a number of", "unknown.
a number of other", "number of other deadenylase", "of other deadenylase enzymes", "other deadenylase enzymes can", "deadenylase enzymes can be", "enzymes can be identified", "can be identified in", "be identified in genomic", "identified in genomic searches.", "genomic searches. one", "searches. one particularly", "one particularly interesting one", "particularly interesting one is", "interesting one is nocturin", "is nocturin a", "nocturin a protein", "a protein that is", "protein that is related", "that is related to", "is related to the", "related to the ccr", "to the ccr 1", "the ccr 1 deadenylase", "ccr 1 deadenylase and", "1 deadenylase and plays", "deadenylase and plays a", "and plays a role", "plays a role in", "a role in circadian", "role in circadian rhythms.
there", "in circadian rhythms.
there is", "circadian rhythms.
there is also", "rhythms.
there is also evidence", "is also evidence for", "also evidence for networking", "evidence for networking between", "for networking between deadenylation", "networking between deadenylation and", "between deadenylation and other", "deadenylation and other aspects", "and other aspects of", "other aspects of gene", "aspects of gene expression.", "of gene expression. ccr4", "gene expression. ccr4 not", "ccr4 not for", "not for example", "for example is", "example is known", "is known to be", "known to be a", "to be a transcription", "be a transcription factor.", "a transcription factor. parn", "transcription factor. parn is", "factor. parn is part", "parn is part of", "is part of a", "part of a complex", "of a complex that", "a complex that regulates", "complex that regulates poly", "that regulates poly a", "a tail length", "tail length and hence", "length and hence translation", "and hence translation in", "hence translation in developing", "translation in developing oocytes.", "deadenylation of mrna proceeds in", "of mrna proceeds in two", "mrna proceeds in two steps.", "proceeds in two steps. according", "in two steps. according to", "two steps. according to current", "steps. according to current models", "to current models in", "current models in the", "models in the first", "in the first step the", "the first step the poly", "first step the poly a", "the poly a tail", "poly a tail is", "a tail is shortened", "tail is shortened from about", "is shortened from about 200", "shortened from about 200 adenosine", "from about 200 adenosine residues", "about 200 adenosine residues to", "200 adenosine residues to about", "adenosine residues to about 80", "residues to about 80 residues", "to about 80 residues by", "about 80 residues by the", "80 residues by the pan2", "residues by the pan2 pan3", "by the pan2 pan3 complex.", "the pan2 pan3 complex. in", "pan2 pan3 complex. in the", "pan3 complex. in the second", "complex. in the second step", "in the second step the", "the second step the poly", "second step the poly a", "a tail is further", "tail is further shortened to", "is further shortened to 10", "further shortened to 10 15", "shortened to 10 15 residues", "to 10 15 residues by", "10 15 residues by either", "15 residues by either the", "residues by either the ccr4", "by either the ccr4 not", "either the ccr4 not complex", "the ccr4 not complex or", "ccr4 not complex or by", "not complex or by the", "complex or by the parn", "or by the parn exoribonuclease.", "by the parn exoribonuclease. how", "the parn exoribonuclease. how a", "parn exoribonuclease. how a particular", "exoribonuclease. how a particular mrna", "how a particular mrna is", "a particular mrna is targeted", "particular mrna is targeted to", "mrna is targeted to ccr4", "is targeted to ccr4 not", "targeted to ccr4 not or", "to ccr4 not or parn", "ccr4 not or parn is", "not or parn is unknown.
a", "or parn is unknown.
a number", "parn is unknown.
a number of", "is unknown.
a number of other", "unknown.
a number of other deadenylase", "number of other deadenylase enzymes", "of other deadenylase enzymes can", "other deadenylase enzymes can be", "deadenylase enzymes can be identified", "enzymes can be identified in", "can be identified in genomic", "be identified in genomic searches.", "in genomic searches. one", "genomic searches. one particularly", "searches. one particularly interesting", "one particularly interesting one is", "particularly interesting one is nocturin", "one is nocturin a", "is nocturin a protein", "nocturin a protein that", "a protein that is related", "protein that is related to", "that is related to the", "is related to the ccr", "related to the ccr 1", "to the ccr 1 deadenylase", "the ccr 1 deadenylase and", "ccr 1 deadenylase and plays", "1 deadenylase and plays a", "deadenylase and plays a role", "and plays a role in", "plays a role in circadian", "a role in circadian rhythms.
there", "role in circadian rhythms.
there is", "in circadian rhythms.
there is also", "circadian rhythms.
there is also evidence", "rhythms.
there is also evidence for", "is also evidence for networking", "also evidence for networking between", "evidence for networking between deadenylation", "for networking between deadenylation and", "networking between deadenylation and other", "between deadenylation and other aspects", "deadenylation and other aspects of", "and other aspects of gene", "other aspects of gene expression.", "aspects of gene expression. ccr4", "of gene expression. ccr4 not", "expression. ccr4 not for", "ccr4 not for example", "for example is known", "example is known to", "is known to be a", "known to be a transcription", "to be a transcription factor.", "be a transcription factor. parn", "a transcription factor. parn is", "transcription factor. parn is part", "factor. parn is part of", "parn is part of a", "is part of a complex", "part of a complex that", "of a complex that regulates", "a complex that regulates poly", "complex that regulates poly a", "regulates poly a tail", "poly a tail length", "a tail length and", "tail length and hence translation", "length and hence translation in", "and hence translation in developing", "hence translation in developing oocytes." ] }, { "record_id": "GLY_000594_1_368", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "430039", "r hsa", "hsa 430039", "r hsa 430039" ] }, { "record_id": "GLY_000594_1_368", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna decay", "decay by", "by 5'", "5' to", "to 3'", "3' exoribonuclease", "mrna decay by", "decay by 5'", "by 5' to", "5' to 3'", "to 3' exoribonuclease", "mrna decay by 5'", "decay by 5' to", "by 5' to 3'", "5' to 3' exoribonuclease", "mrna decay by 5' to", "decay by 5' to 3'", "by 5' to 3' exoribonuclease", "degradation of", "of mrna", "mrna from", "from 5'", "3' occurs", "occurs in", "in three", "three steps.", "steps. first", "the mrna", "mrna is", "is bound", "bound at", "at its", "its 3'", "3' end", "end 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in the collecting", "the collecting duct", "collecting duct epithelial", "duct epithelial cells", "epithelial cells have", "cells have aqp2", "have aqp2 on", "aqp2 on their", "on their apical", "their apical surface", "apical surface and", "surface and aqp3", "and aqp3 and", "aqp3 and aqp4", "and aqp4 on", "aqp4 on their", "on their basolateral", "their basolateral surface", "basolateral surface to", "surface to transport", "to transport water", "transport water across", "water across the", "across the epithelium.", "the epithelium. the", "epithelium. the permeability", "the permeability of", "permeability of the", "of the epithelium", "the epithelium is", "epithelium is regulated", "is regulated by", "regulated by vasopressin", "vasopressin which", "which activates the", "activates the phosphorylation", "the phosphorylation and", "phosphorylation and subsequent", "and subsequent translocation", "subsequent translocation of", "translocation of aqp2", "of aqp2 from", "aqp2 from intracellular", "from intracellular vesicles", "intracellular vesicles to", "vesicles to the", "to the plasma", "the plasma membrane.", "in the kidney water", "the kidney water and", "kidney water and solutes", "water and solutes are", "and solutes are passed", "solutes are passed out", "are passed out of", "passed out of the", "out of the bloodstream", "of the bloodstream and", "the bloodstream and into", "bloodstream and into the", "and into the proximal", "into the proximal tubule", "the proximal tubule via", "proximal tubule via the", "tubule via the slit", "via the slit like", "the slit like structure", "slit like structure formed", "like structure formed by", "structure formed by nephrin", "formed by nephrin in", "by nephrin in the", "nephrin in the glomerulus.", "in the glomerulus. water", "the glomerulus. water is", "glomerulus. water is reabsorbed", "water is reabsorbed from", "is reabsorbed from the", "reabsorbed from the filtrate", "from the filtrate during", "the filtrate during its", "filtrate during its transit", "during its transit through", "its transit through the", "transit through the proximal", "through the proximal tubule", "proximal tubule the", "tubule the descending", "the descending loop of", "descending loop of henle", "of henle the", "henle the distal", "the distal convoluted tubule", "convoluted tubule and", "and the collecting duct.
aquaporin", "the collecting duct.
aquaporin 1", "duct.
aquaporin 1 aqp1", "aqp1 in the", "in the proximal tubule", "the proximal tubule and", "proximal tubule and the", "tubule and the descending", "and the descending thin", "the descending thin limb", "descending thin limb of", "thin limb of henle", "limb of henle is", "of henle is responsible", "henle is responsible for", "is responsible for about", "responsible for about 90%", "for about 90% of", "about 90% of reabsorption", "of reabsorption as", "reabsorption as estimated", "as estimated from mouse", "estimated from mouse knockouts", "from mouse knockouts of", "mouse knockouts of aqp1", "knockouts of aqp1 .", "of aqp1 . aqp1", "aqp1 . aqp1 is", ". aqp1 is located", "aqp1 is located on", "is located on both", "located on both the", "on both the apical", "both the apical and", "the apical and basolateral", "apical and basolateral surface", "and basolateral surface of", "basolateral surface of epithelial", "surface of epithelial cells", "of epithelial cells and", "epithelial cells and thus", "cells and thus transports", "and thus transports water", "thus transports water through", "transports water through the", "water through the epithelium", "through the epithelium and", "the epithelium and back", "epithelium and back into", "and back into the", "back into the bloodstream.
in", "into the bloodstream.
in the", "the bloodstream.
in the collecting", "bloodstream.
in the collecting duct", "the collecting duct epithelial", "collecting duct epithelial cells", "duct epithelial cells have", "epithelial cells have aqp2", "cells have aqp2 on", "have aqp2 on their", "aqp2 on their apical", "on their apical surface", "their apical surface and", "apical surface and aqp3", "surface and aqp3 and", "and aqp3 and aqp4", "aqp3 and aqp4 on", "and aqp4 on their", "aqp4 on their basolateral", "on their basolateral surface", "their basolateral surface to", "basolateral surface to transport", "surface to transport water", "to transport water across", "transport water across the", "water across the epithelium.", "across the epithelium. the", "the epithelium. the permeability", "epithelium. the permeability of", "the permeability of the", "permeability of the epithelium", "of the epithelium is", "the epithelium is regulated", "epithelium is regulated by", "is regulated by vasopressin", "by vasopressin which", "vasopressin which activates", "which activates the phosphorylation", "activates the phosphorylation and", "the phosphorylation and subsequent", "phosphorylation and subsequent translocation", "and subsequent translocation of", "subsequent translocation of aqp2", "translocation of aqp2 from", "of aqp2 from intracellular", "aqp2 from intracellular vesicles", "from intracellular vesicles to", "intracellular vesicles to the", "vesicles to the plasma", "to the plasma membrane.", "in the kidney water and", "the kidney water and solutes", "kidney water and solutes are", "water and solutes are passed", "and solutes are passed out", "solutes are passed out of", "are passed out of the", "passed out of the bloodstream", "out of the bloodstream and", "of the bloodstream and into", "the bloodstream and into the", "bloodstream and into the proximal", "and into the proximal tubule", "into the proximal tubule via", "the proximal tubule via the", "proximal tubule via the slit", "tubule via the slit like", "via the slit like structure", "the slit like structure formed", "slit like structure formed by", "like structure formed by nephrin", "structure formed by nephrin in", "formed by nephrin in the", "by nephrin in the glomerulus.", "nephrin in the glomerulus. water", "in the glomerulus. water is", "the glomerulus. water is reabsorbed", "glomerulus. water is reabsorbed from", "water is reabsorbed from the", "is reabsorbed from the filtrate", "reabsorbed from the filtrate during", "from the filtrate during its", "the filtrate during its transit", "filtrate during its transit through", "during its transit through the", "its transit through the proximal", "transit through the proximal tubule", "the proximal tubule the", "proximal tubule the descending", "tubule the descending loop", "the descending loop of henle", "loop of henle the", "of henle the distal", "henle the distal convoluted", "distal convoluted tubule and", "convoluted tubule and the", "tubule and the collecting", "and the collecting duct.
aquaporin 1", "collecting duct.
aquaporin 1 aqp1", "1 aqp1 in", "aqp1 in the proximal", "in the proximal tubule and", "the proximal tubule and the", "proximal tubule and the descending", "tubule and the descending thin", "and the descending thin limb", "the descending thin limb of", "descending thin limb of henle", "thin limb of henle is", "limb of henle is responsible", "of henle is responsible for", "henle is responsible for about", "is responsible for about 90%", "responsible for about 90% of", "for about 90% of reabsorption", "90% of reabsorption as", "of reabsorption as estimated", "reabsorption as estimated from", "as estimated from mouse knockouts", "estimated from mouse knockouts of", "from mouse knockouts of aqp1", "mouse knockouts of aqp1 .", "knockouts of aqp1 . aqp1", "of aqp1 . aqp1 is", "aqp1 . aqp1 is located", ". aqp1 is located on", "aqp1 is located on both", "is located on both the", "located on both the apical", "on both the apical and", "both the apical and basolateral", "the apical and basolateral surface", "apical and basolateral surface of", "and basolateral surface of epithelial", "basolateral surface of epithelial cells", "surface of epithelial cells and", "of epithelial cells and thus", "epithelial cells and thus transports", "cells and thus transports water", "and thus transports water through", "thus transports water through the", "transports water through the epithelium", "water through the epithelium and", "through the epithelium and back", "the epithelium and back into", "epithelium and back into the", "and back into the bloodstream.
in", "back into the bloodstream.
in the", "into the bloodstream.
in the collecting", "the bloodstream.
in the collecting duct", "bloodstream.
in the collecting duct epithelial", "the collecting duct epithelial cells", "collecting duct epithelial cells have", "duct epithelial cells have aqp2", "epithelial cells have aqp2 on", "cells have aqp2 on their", "have aqp2 on their apical", "aqp2 on their apical surface", "on their apical surface and", "their apical surface and aqp3", "apical surface and aqp3 and", "surface and aqp3 and aqp4", "and aqp3 and aqp4 on", "aqp3 and aqp4 on their", "and aqp4 on their basolateral", "aqp4 on their basolateral surface", "on their basolateral surface to", "their basolateral surface to transport", "basolateral surface to transport water", "surface to transport water across", "to transport water across the", "transport water across the epithelium.", "water across the epithelium. the", "across the epithelium. the permeability", "the epithelium. the permeability of", "epithelium. the permeability of the", "the permeability of the epithelium", "permeability of the epithelium is", "of the epithelium is regulated", "the epithelium is regulated by", "epithelium is regulated by vasopressin", "regulated by vasopressin which", "by vasopressin which activates", "vasopressin which activates the", "which activates the phosphorylation and", "activates the phosphorylation and subsequent", "the phosphorylation and subsequent translocation", "phosphorylation and subsequent translocation of", "and subsequent translocation of aqp2", "subsequent translocation of aqp2 from", "translocation of aqp2 from intracellular", "of aqp2 from intracellular vesicles", "aqp2 from intracellular vesicles to", "from intracellular vesicles to the", "intracellular vesicles to the plasma", "vesicles to the plasma membrane." ] }, { "record_id": "GLY_000594_1_371", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "432047", "r hsa", "hsa 432047", "r hsa 432047" ] }, { "record_id": "GLY_000594_1_371", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "passive transport", "transport by", "by aquaporins", "passive transport by", "transport by aquaporins", "passive transport by aquaporins", "are six", "six pass", "pass transmembrane", "transmembrane proteins", "proteins that", "that form", "form channels", "channels in", "in membranes.", "membranes. each", "each monomer", "monomer contains", "contains a", "a central", "central channel", "channel formed", "formed in", "in part", "part by", "by two", "two asparagine", "asparagine proline", "proline alanine", "alanine motifs", "npa boxes", "that confer", "confer selectivity", "selectivity for", "for water", "water and/or", "and/or solutes.", "solutes. the", "the monomers", "monomers assemble", "assemble into", "into tetramers.", "tetramers. during", "during passive", "aquaporins most", "most aquaporins", "i.e. aqp0/mip", "transport water", "water into", "into and", "and out", "out of", "of cells", "cells according", "according to", "to the", "the osmotic", "osmotic gradient", "gradient across", "across the", "the membrane.", "membrane. four", "four aquaporins", "the aquaglyceroporins", "aquaglyceroporins aqp3", "conduct glycerol", "three aquaporins", "conduct urea", "and one", "one aquaporin", "conducts anions", "especially nitrate.", "nitrate. aqp8", "aqp8 also", "also conducts", "conducts ammonia", "ammonia in", "in addition", "addition to", "to water.
aqp11", "water.
aqp11 and", "and aqp12", "classified as", "as group", "group iii", "iii aquaporins", "were identified", "identified as", "as a", "a result", "result of", "of the", "the genome", "genome sequencing", "sequencing project", "project and", "and are", "are characterized", "characterized by", "by having", "having variations", "variations in", "in the", "the first", "first npa", "npa box", "box when", "when compared", "compared to", "to more", "more traditional", "traditional aquaporins.", "aquaporins. additionally", "a conserved", "conserved cysteine", "cysteine residue", "residue is", "is present", "present about", "about 9", "9 amino", "amino acids", "acids downstream", "downstream from", "from the", "the second", "second npa", "box and", "and this", "this cysteine", "cysteine is", "is considered", "considered indicative", "indicative of", "of group", "iii aquaporins.", "aquaporins. purified", "purified aqp11", "aqp11 incorporated", "incorporated into", "into liposomes", "liposomes showed", "showed water", "water transport.", "transport. knockout", "knockout mice", "mice lacking", "lacking aqp11", "aqp11 had", "had fatal", "fatal cyst", "cyst formation", "formation in", "the proximal", "proximal tubule", "tubule of", "the kidney.", "kidney. exogenously", "exogenously expressed", "expressed aqp12", "aqp12 showed", "showed intracellular", "intracellular localization.", "localization. aqp12", "aqp12 is", "is expressed", "expressed exclusively", "exclusively in", "in pancreatic", "pancreatic acinar", "acinar cells.
aquaporins", "cells.
aquaporins are", "are important", "important in", "in fluid", "fluid and", "and solute", "solute transport", "transport in", "in various", "various tissues.", "tissues. during", "during transport", "transport of", "of glycerol", "glycerol from", "from adipocytes", "adipocytes to", "the liver", "liver by", "glycerol generated", "generated by", "by triglyceride", "triglyceride hydrolysis", "hydrolysis is", "is exported", "exported from", "adipocytes by", "by aqp7", "aqp7 and", "and is", "is imported", "imported into", "into liver", "liver cells", "cells via", "via aqp9.", "aqp9. aqp1", "aqp1 plays", "plays a", "a role", "role in", "in forming", "forming cerebrospinal", "cerebrospinal fluid", "and aqp1", "and aqp9", "aqp9 appear", "appear to", "to be", "be important", "in maintaining", "maintaining fluid", "fluid balance", "balance in", "the brain.", "brain. aqp0", "and aqp11", "aqp11 play", "play roles", "roles in", "the physiology", "physiology of", "the hepatobiliary", "hepatobiliary tract.
in", "tract.
in the", "the kidney", "water and", "and solutes", "solutes are", "are passed", "passed out", "the bloodstream", "bloodstream and", "and into", "into the", "tubule via", "via the", "the slit", "slit like", "like structure", "structure formed", "formed by", "by nephrin", "nephrin in", "the glomerulus.", "glomerulus. water", "water is", "is reabsorbed", "reabsorbed from", "the filtrate", "filtrate during", "during its", "its transit", "transit through", "through the", "the descending", "descending loop", "loop of", "of henle", "the distal", "distal convoluted", "convoluted tubule", "and the", "the collecting", "collecting duct.", "duct. aquaporin", "aquaporin 1", "tubule and", "descending thin", "thin limb", "limb of", "henle is", "is responsible", "responsible for", "for about", "about 90%", "90% of", "of reabsorption", "as estimated", "estimated from", "from mouse", "mouse knockouts", "knockouts of", "of aqp1", "aqp1 .", ". aqp1", "aqp1 is", "is located", "located on", "on both", "both the", "the apical", "apical and", "and basolateral", "basolateral surface", "surface of", "of epithelial", "epithelial cells", "cells and", "and thus", "thus transports", "transports water", "water through", "the epithelium", "epithelium and", "and back", "back into", "the bloodstream.", "bloodstream. in", "collecting duct", "duct epithelial", "cells have", "have aqp2", "aqp2 on", "on their", "their apical", "apical surfaces", "surfaces and", "and aqp3", "aqp3 and", "and aqp4", "aqp4 on", "their basolateral", "basolateral surfaces", "surfaces to", "to transport", "water across", "the epithelium.", "epithelium. vasopressin", "vasopressin regulates", "regulates renal", "renal water", "water homeostasis", "homeostasis via", "via aquaporins", "aquaporins by", "by regulating", "regulating the", "the permeability", "permeability of", "epithelium through", "through activation", "activation of", "of a", "a signaling", "signaling cascade", "cascade leading", "leading to", "the phosphorylation", "phosphorylation of", "of aqp2", "aqp2 and", "and its", "its translocation", "translocation from", "from intracellular", "intracellular vesicles", "vesicles to", "apical membrane", "membrane of", "of collecting", "duct cells.
here", "three views", "views of", "of aquaporin", "aquaporin mediated", "mediated transport", "transport have", "have been", "been annotated:", "annotated: a", "a generic", "generic view", "view of", "of transport", "transport mediated", "mediated by", "by the", "the various", "various families", "families of", "of aquaporins", "aquaporins independent", "independent of", "of tissue", "tissue type", "a view", "the role", "role of", "of specific", "specific aquaporins", "aquaporins in", "in maintenance", "maintenance of", "of renal", "water balance", "and a", "in glycerol", "glycerol transport", "transport from", "aquaporins .", "aquaporins aqp's", "aqp's are", "are six pass", "six pass transmembrane", "pass transmembrane proteins", "transmembrane proteins that", "proteins that form", "that form channels", "form channels in", "channels in membranes.", "in membranes. each", "membranes. each monomer", "each monomer contains", "monomer contains a", "contains a central", "a central channel", "central channel formed", "channel formed in", "formed in part", "in part by", "part by two", "by two asparagine", "two asparagine proline", "asparagine proline alanine", "proline alanine motifs", "motifs npa", "boxes that", "that confer selectivity", "confer selectivity for", "selectivity for water", "for water and/or", "water and/or solutes.", "and/or solutes. the", "solutes. the monomers", "the monomers assemble", "monomers assemble into", "assemble into tetramers.", "into tetramers. during", "tetramers. during passive", "during passive transport", "by aquaporins most", "aquaporins most aquaporins", "aquaporins i.e.", "aqp0/mip aqp1", "aqp1 aqp2", "aqp2 aqp3", "aqp3 aqp4", "aqp4 aqp5", "aqp5 aqp7", "aqp7 aqp8", "aqp8 aqp9", "aqp9 aqp10", "aqp10 transport", "transport water into", "water into and", "into and out", "and out of", "out of cells", "of cells according", "cells according to", "according to the", "to the osmotic", "the osmotic gradient", "osmotic gradient across", "gradient across the", "across the membrane.", "the membrane. four", "membrane. four aquaporins", "aquaporins the", "the aquaglyceroporins aqp3", "aqp3 aqp7", "aqp10 conduct", "glycerol three", "aquaporins aqp7", "aqp7 aqp9", "urea and", "and one aquaporin", "aquaporin aqp6", "aqp6 conducts", "anions especially", "especially nitrate. aqp8", "nitrate. aqp8 also", "aqp8 also conducts", "also conducts ammonia", "conducts ammonia in", "ammonia in addition", "in addition to", "addition to water.
aqp11", "to water.
aqp11 and", "water.
aqp11 and aqp12", "aqp12 classified", "classified as group", "as group iii", "group iii aquaporins", "aquaporins were", "were identified as", "identified as a", "as a result", "a result of", "result of the", "of the genome", "the genome sequencing", "genome sequencing project", "sequencing project and", "project and are", "and are characterized", "are characterized by", "characterized by having", "by having variations", "having variations in", "variations in the", "in the first", "the first npa", "first npa box", "npa box when", "box when compared", "when compared to", "compared to more", "to more traditional", "more traditional aquaporins.", "traditional aquaporins. additionally", "additionally a", "a conserved cysteine", "conserved cysteine residue", "cysteine residue is", "residue is present", "is present about", "present about 9", "about 9 amino", "9 amino acids", "amino acids downstream", "acids downstream from", "downstream from the", "from the second", "the second npa", "second npa box", "npa box and", "box and this", "and this cysteine", "this cysteine is", "cysteine is considered", "is considered indicative", "considered indicative of", "indicative of group", "of group iii", "group iii aquaporins.", "iii aquaporins. purified", "aquaporins. purified aqp11", "purified aqp11 incorporated", "aqp11 incorporated into", "incorporated into liposomes", "into liposomes showed", "liposomes showed water", "showed water transport.", "water transport. knockout", "transport. knockout mice", "knockout mice lacking", "mice lacking aqp11", "lacking aqp11 had", "aqp11 had fatal", "had fatal cyst", "fatal cyst formation", "cyst formation in", "formation in the", "in the proximal", "the proximal tubule", "proximal tubule of", "tubule of the", "of the kidney.", "the kidney. exogenously", "kidney. exogenously expressed", "exogenously expressed aqp12", "expressed aqp12 showed", "aqp12 showed intracellular", "showed intracellular localization.", "intracellular localization. aqp12", "localization. aqp12 is", "aqp12 is expressed", "is expressed exclusively", "expressed exclusively in", "exclusively in pancreatic", "in pancreatic acinar", "pancreatic acinar cells.
aquaporins", "acinar cells.
aquaporins are", "cells.
aquaporins are important", "are important in", "important in fluid", "in fluid and", "fluid and solute", "and solute transport", "solute transport in", "transport in various", "in various tissues.", "various tissues. during", "tissues. during transport", "during transport of", "transport of glycerol", "of glycerol from", "glycerol from adipocytes", "from adipocytes to", "adipocytes to the", "to the liver", "the liver by", "liver by aquaporins", "aquaporins glycerol", "glycerol generated by", "generated by triglyceride", "by triglyceride hydrolysis", "triglyceride hydrolysis is", "hydrolysis is exported", "is exported from", "exported from adipocytes", "from adipocytes by", "adipocytes by aqp7", "by aqp7 and", "aqp7 and is", "and is imported", "is imported into", "imported into liver", "into liver cells", "liver cells via", "cells via aqp9.", "via aqp9. aqp1", "aqp9. aqp1 plays", "aqp1 plays a", "plays a role", "a role in", "role in forming", "in forming cerebrospinal", "forming cerebrospinal fluid", "cerebrospinal fluid and", "fluid and aqp1", "aqp1 aqp4", "aqp4 and", "and aqp9 appear", "aqp9 appear to", "appear to be", "to be important", "be important in", "important in maintaining", "in maintaining fluid", "maintaining fluid balance", "fluid balance in", "balance in the", "in the brain.", "the brain. aqp0", "aqp0 aqp1", "aqp1 aqp3", "aqp4 aqp8", "aqp9 and", "and aqp11 play", "aqp11 play roles", "play roles in", "roles in the", "in the physiology", "the physiology of", "physiology of the", "of the hepatobiliary", "the hepatobiliary tract.
in", "hepatobiliary tract.
in the", "tract.
in the kidney", "kidney water", "water and solutes", "and solutes are", "solutes are passed", "are passed out", "passed out of", "out of the", "of the bloodstream", "the bloodstream and", "bloodstream and into", "and into the", "into the proximal", "proximal tubule via", "tubule via the", "via the slit", "the slit like", "slit like structure", "like structure formed", "structure formed by", "formed by nephrin", "by nephrin in", "nephrin in the", "in the glomerulus.", "the glomerulus. water", "glomerulus. water is", "water is reabsorbed", "is reabsorbed from", "reabsorbed from the", "from the filtrate", "the filtrate during", "filtrate during its", "during its transit", "its transit through", "transit through the", "through the proximal", "tubule the", "the descending loop", "descending loop of", "loop of henle", "henle the", "the distal convoluted", "distal convoluted tubule", "and the collecting", "the collecting duct.", "collecting duct. aquaporin", "duct. aquaporin 1", "1 aqp1", "aqp1 in", "proximal tubule and", "tubule and the", "and the descending", "the descending thin", "descending thin limb", "thin limb of", "limb of henle", "of henle is", "henle is responsible", "is responsible for", "responsible for about", "for about 90%", "about 90% of", "90% of reabsorption", "reabsorption as", "as estimated from", "estimated from mouse", "from mouse knockouts", "mouse knockouts of", "knockouts of aqp1", "of aqp1 .", "aqp1 . aqp1", ". aqp1 is", "aqp1 is located", "is located on", "located on both", "on both the", "both the apical", "the apical and", "apical and basolateral", "and basolateral surface", "basolateral surface of", "surface of epithelial", "of epithelial cells", "epithelial cells and", "cells and thus", "and thus transports", "thus transports water", "transports water through", "water through the", "through the epithelium", "the epithelium and", "epithelium and back", "and back into", "back into the", "into the bloodstream.", "the bloodstream. in", "bloodstream. in the", "in the collecting", "the collecting duct", "collecting duct epithelial", "duct epithelial cells", "epithelial cells have", "cells have aqp2", "have aqp2 on", "aqp2 on their", "on their apical", "their apical surfaces", "apical surfaces and", "surfaces and aqp3", "and aqp3 and", "aqp3 and aqp4", "and aqp4 on", "aqp4 on their", "on their basolateral", "their basolateral surfaces", "basolateral surfaces to", "surfaces to transport", "to transport water", "transport water across", "water across the", "across the epithelium.", "the epithelium. vasopressin", "epithelium. vasopressin regulates", "vasopressin regulates renal", "regulates renal water", "renal water homeostasis", "water homeostasis via", "homeostasis via aquaporins", "via aquaporins by", "aquaporins by regulating", "by regulating the", "regulating the permeability", "the permeability of", "permeability of the", "of the epithelium", "the epithelium through", "epithelium through activation", "through activation of", "activation of a", "of a signaling", "a signaling cascade", "signaling cascade leading", "cascade leading to", "leading to the", "to the phosphorylation", "the phosphorylation of", "phosphorylation of aqp2", "of aqp2 and", "aqp2 and its", "and its translocation", "its translocation from", "translocation from intracellular", "from intracellular vesicles", "intracellular vesicles to", "vesicles to the", "to the apical", "the apical membrane", "apical membrane of", "membrane of collecting", "of collecting duct", "collecting duct cells.
here", "cells.
here three", "three views of", "views of aquaporin", "of aquaporin mediated", "aquaporin mediated transport", "mediated transport have", "transport have been", "have been annotated:", "been annotated: a", "annotated: a generic", "a generic view", "generic view of", "view of transport", "of transport mediated", "transport mediated by", "mediated by the", "by the various", "the various families", "various families of", "families of aquaporins", "of aquaporins independent", "aquaporins independent of", "independent of tissue", "of tissue type", "type passive", "a view of", "view of the", "of the role", "the role of", "role of specific", "of specific aquaporins", "specific aquaporins in", "aquaporins in maintenance", "in maintenance of", "maintenance of renal", "of renal water", "renal water balance", "balance vasopressin", "and a view", "aquaporins in glycerol", "in glycerol transport", "glycerol transport from", "transport from adipocytes", "liver transport", "by aquaporins .", "aqp's are six", "are six pass transmembrane", "six pass transmembrane proteins", "pass transmembrane proteins that", "transmembrane proteins that form", "proteins that form channels", "that form channels in", "form channels in membranes.", "channels in membranes. each", "in membranes. each monomer", "membranes. each monomer contains", "each monomer contains a", "monomer contains a central", "contains a central channel", "a central channel formed", "central channel formed in", "channel formed in part", "formed in part by", "in part by two", "part by two asparagine", "by two asparagine proline", "two asparagine proline alanine", "asparagine proline alanine motifs", "alanine motifs npa", "motifs npa boxes", "npa boxes that", "boxes that confer", "that confer selectivity for", "confer selectivity for water", "selectivity for water and/or", "for water and/or solutes.", "water and/or solutes. the", "and/or solutes. the monomers", "solutes. the monomers assemble", "the monomers assemble into", "monomers assemble into tetramers.", "assemble into tetramers. during", "into tetramers. during passive", "tetramers. during passive transport", "during passive transport by", "transport by aquaporins most", "by aquaporins most aquaporins", "most aquaporins i.e.", "aquaporins i.e. aqp0/mip", "i.e. aqp0/mip aqp1", "aqp10 transport water", "transport water into and", "water into and out", "into and out of", "and out of cells", "out of cells according", "of cells according to", "cells according to the", "according to the osmotic", "to the osmotic gradient", "the osmotic gradient across", "osmotic gradient across the", "gradient across the membrane.", "across the membrane. four", "the membrane. four aquaporins", "four aquaporins the", "aquaporins the aquaglyceroporins", "aquaglyceroporins aqp3 aqp7", "aqp10 conduct glycerol", "conduct glycerol three", "glycerol three aquaporins", "three aquaporins aqp7", "aqp10 conduct urea", "conduct urea and", "urea and one", "one aquaporin aqp6", "aqp6 conducts anions", "conducts anions especially", "anions especially nitrate.", "especially nitrate. aqp8 also", "nitrate. aqp8 also conducts", "aqp8 also conducts ammonia", "also conducts ammonia in", "conducts ammonia in addition", "ammonia in addition to", "in addition to water.
aqp11", "addition to water.
aqp11 and", "to water.
aqp11 and aqp12", "and aqp12 classified", "aqp12 classified as", "classified as group iii", "as group iii aquaporins", "iii aquaporins were", "aquaporins were identified", "were identified as a", "identified as a result", "as a result of", "a result of the", "result of the genome", "of the genome sequencing", "the genome sequencing project", "genome sequencing project and", "sequencing project and are", "project and are characterized", "and are characterized by", "are characterized by having", "characterized by having variations", "by having variations in", "having variations in the", "variations in the first", "in the first npa", "the first npa box", "first npa box when", "npa box when compared", "box when compared to", "when compared to more", "compared to more traditional", "to more traditional aquaporins.", "more traditional aquaporins. additionally", "aquaporins. additionally a", "additionally a conserved", "a conserved cysteine residue", "conserved cysteine residue is", "cysteine residue is present", "residue is present about", "is present about 9", "present about 9 amino", "about 9 amino acids", "9 amino acids downstream", "amino acids downstream from", "acids downstream from the", "downstream from the second", "from the second npa", "the second npa box", "second npa box and", "npa box and this", "box and this cysteine", "and this cysteine is", "this cysteine is considered", "cysteine is considered indicative", "is considered indicative of", "considered indicative of group", "indicative of group iii", "of group iii aquaporins.", "group iii aquaporins. purified", "iii aquaporins. purified aqp11", "aquaporins. purified aqp11 incorporated", "purified aqp11 incorporated into", "aqp11 incorporated into liposomes", "incorporated into liposomes showed", "into liposomes showed water", "liposomes showed water transport.", "showed water transport. knockout", "water transport. knockout mice", "transport. knockout mice lacking", "knockout mice lacking aqp11", "mice lacking aqp11 had", "lacking aqp11 had fatal", "aqp11 had fatal cyst", "had fatal cyst formation", "fatal cyst formation in", "cyst formation in the", "formation in the proximal", "in the proximal tubule", "the proximal tubule of", "proximal tubule of the", "tubule of the kidney.", "of the kidney. exogenously", "the kidney. exogenously expressed", "kidney. exogenously expressed aqp12", "exogenously expressed aqp12 showed", "expressed aqp12 showed intracellular", "aqp12 showed intracellular localization.", "showed intracellular localization. aqp12", "intracellular localization. aqp12 is", "localization. aqp12 is expressed", "aqp12 is expressed exclusively", "is expressed exclusively in", "expressed exclusively in pancreatic", "exclusively in pancreatic acinar", "in pancreatic acinar cells.
aquaporins", "pancreatic acinar cells.
aquaporins are", "acinar cells.
aquaporins are important", "cells.
aquaporins are important in", "are important in fluid", "important in fluid and", "in fluid and solute", "fluid and solute transport", "and solute transport in", "solute transport in various", "transport in various tissues.", "in various tissues. during", "various tissues. during transport", "tissues. during transport of", "during transport of glycerol", "transport of glycerol from", "of glycerol from adipocytes", "glycerol from adipocytes to", "from adipocytes to the", "adipocytes to the liver", "to the liver by", "the liver by aquaporins", "by aquaporins glycerol", "aquaporins glycerol generated", "glycerol generated by triglyceride", "generated by triglyceride hydrolysis", "by triglyceride hydrolysis is", "triglyceride hydrolysis is exported", "hydrolysis is exported from", "is exported from adipocytes", "exported from adipocytes by", "from adipocytes by aqp7", "adipocytes by aqp7 and", "by aqp7 and is", "aqp7 and is imported", "and is imported into", "is imported into liver", "imported into liver cells", "into liver cells via", "liver cells via aqp9.", "cells via aqp9. aqp1", "via aqp9. aqp1 plays", "aqp9. aqp1 plays a", "aqp1 plays a role", "plays a role in", "a role in forming", "role in forming cerebrospinal", "in forming cerebrospinal fluid", "forming cerebrospinal fluid and", "cerebrospinal fluid and aqp1", "and aqp1 aqp4", "aqp4 and aqp9", "and aqp9 appear to", "aqp9 appear to be", "appear to be important", "to be important in", "be important in maintaining", "important in maintaining fluid", "in maintaining fluid balance", "maintaining fluid balance in", "fluid balance in the", "balance in the brain.", "in the brain. aqp0", "brain. aqp0 aqp1", "aqp9 and aqp11", "and aqp11 play roles", "aqp11 play roles in", "play roles in the", "roles in the physiology", "in the physiology of", "the physiology of the", "physiology of the hepatobiliary", "of the hepatobiliary tract.
in", "the hepatobiliary tract.
in the", "hepatobiliary tract.
in the kidney", "the kidney water", "kidney water and", "water and solutes are", "and solutes are passed", "solutes are passed out", "are passed out of", "passed out of the", "out of the bloodstream", "of the bloodstream and", "the bloodstream and into", "bloodstream and into the", "and into the proximal", "into the proximal tubule", "the proximal tubule via", "proximal tubule via the", "tubule via the slit", "via the slit like", "the slit like structure", "slit like structure formed", "like structure formed by", "structure formed by nephrin", "formed by nephrin in", "by nephrin in the", "nephrin in the glomerulus.", "in the glomerulus. water", "the glomerulus. water is", "glomerulus. water is reabsorbed", "water is reabsorbed from", "is reabsorbed from the", "reabsorbed from the filtrate", "from the filtrate during", "the filtrate during its", "filtrate during its transit", "during its transit through", "its transit through the", "transit through the proximal", "through the proximal tubule", "proximal tubule the", "tubule the descending", "the descending loop of", "descending loop of henle", "of henle the", "henle the distal", "the distal convoluted tubule", "convoluted tubule and", "and the collecting duct.", "the collecting duct. aquaporin", "collecting duct. aquaporin 1", "aquaporin 1 aqp1", "aqp1 in the", "the proximal tubule and", "proximal tubule and the", "tubule and the descending", "and the descending thin", "the descending thin limb", "descending thin limb of", "thin limb of henle", "limb of henle is", "of henle is responsible", "henle is responsible for", "is responsible for about", "responsible for about 90%", "for about 90% of", "about 90% of reabsorption", "of reabsorption as", "reabsorption as estimated", "as estimated from mouse", "estimated from mouse knockouts", "from mouse knockouts of", "mouse knockouts of aqp1", "knockouts of aqp1 .", "of aqp1 . aqp1", "aqp1 . aqp1 is", ". aqp1 is located", "aqp1 is located on", "is located on both", "located on both the", "on both the apical", "both the apical and", "the apical and basolateral", "apical and basolateral surface", "and basolateral surface of", "basolateral surface of epithelial", "surface of epithelial cells", "of epithelial cells and", "epithelial cells and thus", "cells and thus transports", "and thus transports water", "thus transports water through", "transports water through the", "water through the epithelium", "through the epithelium and", "the epithelium and back", "epithelium and back into", "and back into the", "back into the bloodstream.", "into the bloodstream. in", "the bloodstream. in the", "bloodstream. in the collecting", "in the collecting duct", "the collecting duct epithelial", "collecting duct epithelial cells", "duct epithelial cells have", "epithelial cells have aqp2", "cells have aqp2 on", "have aqp2 on their", "aqp2 on their apical", "on their apical surfaces", "their apical surfaces and", "apical surfaces and aqp3", "surfaces and aqp3 and", "and aqp3 and aqp4", "aqp3 and aqp4 on", "and aqp4 on their", "aqp4 on their basolateral", "on their basolateral surfaces", "their basolateral surfaces to", "basolateral surfaces to transport", "surfaces to transport water", "to transport water across", "transport water across the", "water across the epithelium.", "across the epithelium. vasopressin", "the epithelium. vasopressin regulates", "epithelium. vasopressin regulates renal", "vasopressin regulates renal water", "regulates renal water homeostasis", "renal water homeostasis via", "water homeostasis via aquaporins", "homeostasis via aquaporins by", "via aquaporins by regulating", "aquaporins by regulating the", "by regulating the permeability", "regulating the permeability of", "the permeability of the", "permeability of the epithelium", "of the epithelium through", "the epithelium through activation", "epithelium through activation of", "through activation of a", "activation of a signaling", "of a signaling cascade", "a signaling cascade leading", "signaling cascade leading to", "cascade leading to the", "leading to the phosphorylation", "to the phosphorylation of", "the phosphorylation of aqp2", "phosphorylation of aqp2 and", "of aqp2 and its", "aqp2 and its translocation", "and its translocation from", "its translocation from intracellular", "translocation from intracellular vesicles", "from intracellular vesicles to", "intracellular vesicles to the", "vesicles to the apical", "to the apical membrane", "the apical membrane of", "apical membrane of collecting", "membrane of collecting duct", "of collecting duct cells.
here", "duct cells.
here three", "cells.
here three views", "three views of aquaporin", "views of aquaporin mediated", "of aquaporin mediated transport", "aquaporin mediated transport have", "mediated transport have been", "transport have been annotated:", "have been annotated: a", "been annotated: a generic", "annotated: a generic view", "a generic view of", "generic view of transport", "view of transport mediated", "of transport mediated by", "transport mediated by the", "mediated by the various", "by the various families", "the various families of", "various families of aquaporins", "families of aquaporins independent", "of aquaporins independent of", "aquaporins independent of tissue", "independent of tissue type", "tissue type passive", "type passive transport", "aquaporins a", "a view of the", "view of the role", "of the role of", "the role of specific", "role of specific aquaporins", "of specific aquaporins in", "specific aquaporins in maintenance", "aquaporins in maintenance of", "in maintenance of renal", "maintenance of renal water", "of renal water balance", "water balance vasopressin", "balance vasopressin regulates", "aquaporins and", "and a view of", "specific aquaporins in glycerol", "aquaporins in glycerol transport", "in glycerol transport from", "glycerol transport from adipocytes", "transport from adipocytes to", "the liver transport", "liver transport of", "liver by aquaporins .", "aquaporins aqp's are", "aqp's are six pass", "are six pass transmembrane proteins", "six pass transmembrane proteins that", "pass transmembrane proteins that form", "transmembrane proteins that form channels", "proteins that form channels in", "that form channels in membranes.", "form channels in membranes. each", "channels in membranes. each monomer", "in membranes. each monomer contains", "membranes. each monomer contains a", "each monomer contains a central", "monomer contains a central channel", "contains a central channel formed", "a central channel formed in", "central channel formed in part", "channel formed in part by", "formed in part by two", "in part by two asparagine", "part by two asparagine proline", "by two asparagine proline alanine", "two asparagine proline alanine motifs", "proline alanine motifs npa", "alanine motifs npa boxes", "npa boxes that confer", "boxes that confer selectivity", "that confer selectivity for water", "confer selectivity for water and/or", "selectivity for water and/or solutes.", "for water and/or solutes. the", "water and/or solutes. the monomers", "and/or solutes. the monomers assemble", "solutes. the monomers assemble into", "the monomers assemble into tetramers.", "monomers assemble into tetramers. during", "assemble into tetramers. during passive", "into tetramers. during passive transport", "tetramers. during passive transport by", "during passive transport by aquaporins", "passive transport by aquaporins most", "transport by aquaporins most aquaporins", "aquaporins most aquaporins i.e.", "most aquaporins i.e. aqp0/mip", "aqp0/mip aqp1 aqp2", "aqp1 aqp2 aqp3", "aqp2 aqp3 aqp4", "aqp3 aqp4 aqp5", "aqp4 aqp5 aqp7", "aqp5 aqp7 aqp8", "aqp7 aqp8 aqp9", "aqp8 aqp9 aqp10", "aqp9 aqp10 transport", "aqp10 transport water into", "transport water into and out", "water into and out of", "into and out of cells", "and out of cells according", "out of cells according to", "of cells according to the", "cells according to the osmotic", "according to the osmotic gradient", "to the osmotic gradient across", "the osmotic gradient across the", "osmotic gradient across the membrane.", "gradient across the membrane. four", "across the membrane. four aquaporins", "membrane. four aquaporins the", "four aquaporins the aquaglyceroporins", "aquaporins the aquaglyceroporins aqp3", "the aquaglyceroporins aqp3 aqp7", "conduct glycerol three aquaporins", "aquaporins aqp7 aqp9", "aqp7 aqp9 aqp10", "aqp9 aqp10 conduct", "conduct urea and one", "urea and one aquaporin", "and one aquaporin aqp6", "aquaporin aqp6 conducts", "conducts anions especially nitrate.", "anions especially nitrate. aqp8", "especially nitrate. aqp8 also conducts", "nitrate. aqp8 also conducts ammonia", "aqp8 also conducts ammonia in", "also conducts ammonia in addition", "conducts ammonia in addition to", "ammonia in addition to water.
aqp11", "in addition to water.
aqp11 and", "addition to water.
aqp11 and aqp12", "water.
aqp11 and aqp12 classified", "and aqp12 classified as", "aqp12 classified as group", "classified as group iii aquaporins", "group iii aquaporins were", "iii aquaporins were identified", "aquaporins were identified as", "were identified as a result", "identified as a result of", "as a result of the", "a result of the genome", "result of the genome sequencing", "of the genome sequencing project", "the genome sequencing project and", "genome sequencing project and are", "sequencing project and are characterized", "project and are characterized by", "and are characterized by having", "are characterized by having variations", "characterized by having variations in", "by having variations in the", "having variations in the first", "variations in the first npa", "in the first npa box", "the first npa box when", "first npa box when compared", "npa box when compared to", "box when compared to more", "when compared to more traditional", "compared to more traditional aquaporins.", "to more traditional aquaporins. additionally", "traditional aquaporins. additionally a", "aquaporins. additionally a conserved", "additionally a conserved cysteine", "a conserved cysteine residue is", "conserved cysteine residue is present", "cysteine residue is present about", "residue is present about 9", "is present about 9 amino", "present about 9 amino acids", "about 9 amino acids downstream", "9 amino acids downstream from", "amino acids downstream from the", "acids downstream from the second", "downstream from the second npa", "from the second npa box", "the second npa box and", "second npa box and this", "npa box and this cysteine", "box and this cysteine is", "and this cysteine is considered", "this cysteine is considered indicative", "cysteine is considered indicative of", "is considered indicative of group", "considered indicative of group iii", "indicative of group iii aquaporins.", "of group iii aquaporins. purified", "group iii aquaporins. purified aqp11", "iii aquaporins. purified aqp11 incorporated", "aquaporins. purified aqp11 incorporated into", "purified aqp11 incorporated into liposomes", "aqp11 incorporated into liposomes showed", "incorporated into liposomes showed water", "into liposomes showed water transport.", "liposomes showed water transport. knockout", "showed water transport. knockout mice", "water transport. knockout mice lacking", "transport. knockout mice lacking aqp11", "knockout mice lacking aqp11 had", "mice lacking aqp11 had fatal", "lacking aqp11 had fatal cyst", "aqp11 had fatal cyst formation", "had fatal cyst formation in", "fatal cyst formation in the", "cyst formation in the proximal", "formation in the proximal tubule", "in the proximal tubule of", "the proximal tubule of the", "proximal tubule of the kidney.", "tubule of the kidney. exogenously", "of the kidney. exogenously expressed", "the kidney. exogenously expressed aqp12", "kidney. exogenously expressed aqp12 showed", "exogenously expressed aqp12 showed intracellular", "expressed aqp12 showed intracellular localization.", "aqp12 showed intracellular localization. aqp12", "showed intracellular localization. aqp12 is", "intracellular localization. aqp12 is expressed", "localization. aqp12 is expressed exclusively", "aqp12 is expressed exclusively in", "is expressed exclusively in pancreatic", "expressed exclusively in pancreatic acinar", "exclusively in pancreatic acinar cells.
aquaporins", "in pancreatic acinar cells.
aquaporins are", "pancreatic acinar cells.
aquaporins are important", "acinar cells.
aquaporins are important in", "cells.
aquaporins are important in fluid", "are important in fluid and", "important in fluid and solute", "in fluid and solute transport", "fluid and solute transport in", "and solute transport in various", "solute transport in various tissues.", "transport in various tissues. during", "in various tissues. during transport", "various tissues. during transport of", "tissues. during transport of glycerol", "during transport of glycerol from", "transport of glycerol from adipocytes", "of glycerol from adipocytes to", "glycerol from adipocytes to the", "from adipocytes to the liver", "adipocytes to the liver by", "to the liver by aquaporins", "liver by aquaporins glycerol", "by aquaporins glycerol generated", "aquaporins glycerol generated by", "glycerol generated by triglyceride hydrolysis", "generated by triglyceride hydrolysis is", "by triglyceride hydrolysis is exported", "triglyceride hydrolysis is exported from", "hydrolysis is exported from adipocytes", "is exported from adipocytes by", "exported from adipocytes by aqp7", "from adipocytes by aqp7 and", "adipocytes by aqp7 and is", "by aqp7 and is imported", "aqp7 and is imported into", "and is imported into liver", "is imported into liver cells", "imported into liver cells via", "into liver cells via aqp9.", "liver cells via aqp9. aqp1", "cells via aqp9. aqp1 plays", "via aqp9. aqp1 plays a", "aqp9. aqp1 plays a role", "aqp1 plays a role in", "plays a role in forming", "a role in forming cerebrospinal", "role in forming cerebrospinal fluid", "in forming cerebrospinal fluid and", "forming cerebrospinal fluid and aqp1", "fluid and aqp1 aqp4", "aqp1 aqp4 and", "aqp4 and aqp9 appear", "and aqp9 appear to be", "aqp9 appear to be important", "appear to be important in", "to be important in maintaining", "be important in maintaining fluid", "important in maintaining fluid balance", "in maintaining fluid balance in", "maintaining fluid balance in the", "fluid balance in the brain.", "balance in the brain. aqp0", "the brain. aqp0 aqp1", "aqp0 aqp1 aqp3", "aqp1 aqp3 aqp4", "aqp3 aqp4 aqp8", "aqp4 aqp8 aqp9", "aqp8 aqp9 and", "aqp9 and aqp11 play", "and aqp11 play roles in", "aqp11 play roles in the", "play roles in the physiology", "roles in the physiology of", "in the physiology of the", "the physiology of the hepatobiliary", "physiology of the hepatobiliary tract.
in", "of the hepatobiliary tract.
in the", "the hepatobiliary tract.
in the kidney", "tract.
in the kidney water", "the kidney water and", "kidney water and solutes", "water and solutes are passed", "and solutes are passed out", "solutes are passed out of", "are passed out of the", "passed out of the bloodstream", "out of the bloodstream and", "of the bloodstream and into", "the bloodstream and into the", "bloodstream and into the proximal", "and into the proximal tubule", "into the proximal tubule via", "the proximal tubule via the", "proximal tubule via the slit", "tubule via the slit like", "via the slit like structure", "the slit like structure formed", "slit like structure formed by", "like structure formed by nephrin", "structure formed by nephrin in", "formed by nephrin in the", "by nephrin in the glomerulus.", "nephrin in the glomerulus. water", "in the glomerulus. water is", "the glomerulus. water is reabsorbed", "glomerulus. water is reabsorbed from", "water is reabsorbed from the", "is reabsorbed from the filtrate", "reabsorbed from the filtrate during", "from the filtrate during its", "the filtrate during its transit", "filtrate during its transit through", "during its transit through the", "its transit through the proximal", "transit through the proximal tubule", "the proximal tubule the", "proximal tubule the descending", "tubule the descending loop", "the descending loop of henle", "loop of henle the", "of henle the distal", "henle the distal convoluted", "distal convoluted tubule and", "convoluted tubule and the", "tubule and the collecting", "and the collecting duct. aquaporin", "the collecting duct. aquaporin 1", "duct. aquaporin 1 aqp1", "1 aqp1 in", "aqp1 in the proximal", "in the proximal tubule and", "the proximal tubule and the", "proximal tubule and the descending", "tubule and the descending thin", "and the descending thin limb", "the descending thin limb of", "descending thin limb of henle", "thin limb of henle is", "limb of henle is responsible", "of henle is responsible for", "henle is responsible for about", "is responsible for about 90%", "responsible for about 90% of", "for about 90% of reabsorption", "90% of reabsorption as", "of reabsorption as estimated", "reabsorption as estimated from", "as estimated from mouse knockouts", "estimated from mouse knockouts of", "from mouse knockouts of aqp1", "mouse knockouts of aqp1 .", "knockouts of aqp1 . aqp1", "of aqp1 . aqp1 is", "aqp1 . aqp1 is located", ". aqp1 is located on", "aqp1 is located on both", "is located on both the", "located on both the apical", "on both the apical and", "both the apical and basolateral", "the apical and basolateral surface", "apical and basolateral surface of", "and basolateral surface of epithelial", "basolateral surface of epithelial cells", "surface of epithelial cells and", "of epithelial cells and thus", "epithelial cells and thus transports", "cells and thus transports water", "and thus transports water through", "thus transports water through the", "transports water through the epithelium", "water through the epithelium and", "through the epithelium and back", "the epithelium and back into", "epithelium and back into the", "and back into the bloodstream.", "back into the bloodstream. in", "into the bloodstream. in the", "the bloodstream. in the collecting", "bloodstream. in the collecting duct", "in the collecting duct epithelial", "the collecting duct epithelial cells", "collecting duct epithelial cells have", "duct epithelial cells have aqp2", "epithelial cells have aqp2 on", "cells have aqp2 on their", "have aqp2 on their apical", "aqp2 on their apical surfaces", "on their apical surfaces and", "their apical surfaces and aqp3", "apical surfaces and aqp3 and", "surfaces and aqp3 and aqp4", "and aqp3 and aqp4 on", "aqp3 and aqp4 on their", "and aqp4 on their basolateral", "aqp4 on their basolateral surfaces", "on their basolateral surfaces to", "their basolateral surfaces to transport", "basolateral surfaces to transport water", "surfaces to transport water across", "to transport water across the", "transport water across the epithelium.", "water across the epithelium. vasopressin", "across the epithelium. vasopressin regulates", "the epithelium. vasopressin regulates renal", "epithelium. vasopressin regulates renal water", "vasopressin regulates renal water homeostasis", "regulates renal water homeostasis via", "renal water homeostasis via aquaporins", "water homeostasis via aquaporins by", "homeostasis via aquaporins by regulating", "via aquaporins by regulating the", "aquaporins by regulating the permeability", "by regulating the permeability of", "regulating the permeability of the", "the permeability of the epithelium", "permeability of the epithelium through", "of the epithelium through activation", "the epithelium through activation of", "epithelium through activation of a", "through activation of a signaling", "activation of a signaling cascade", "of a signaling cascade leading", "a signaling cascade leading to", "signaling cascade leading to the", "cascade leading to the phosphorylation", "leading to the phosphorylation of", "to the phosphorylation of aqp2", "the phosphorylation of aqp2 and", "phosphorylation of aqp2 and its", "of aqp2 and its translocation", "aqp2 and its translocation from", "and its translocation from intracellular", "its translocation from intracellular vesicles", "translocation from intracellular vesicles to", "from intracellular vesicles to the", "intracellular vesicles to the apical", "vesicles to the apical membrane", "to the apical membrane of", "the apical membrane of collecting", "apical membrane of collecting duct", "membrane of collecting duct cells.
here", "collecting duct cells.
here three", "duct cells.
here three views", "cells.
here three views of", "three views of aquaporin mediated", "views of aquaporin mediated transport", "of aquaporin mediated transport have", "aquaporin mediated transport have been", "mediated transport have been annotated:", "transport have been annotated: a", "have been annotated: a generic", "been annotated: a generic view", "annotated: a generic view of", "a generic view of transport", "generic view of transport mediated", "view of transport mediated by", "of transport mediated by the", "transport mediated by the various", "mediated by the various families", "by the various families of", "the various families of aquaporins", "various families of aquaporins independent", "families of aquaporins independent of", "of aquaporins independent of tissue", "aquaporins independent of tissue type", "of tissue type passive", "tissue type passive transport", "type passive transport by", "by aquaporins a", "aquaporins a view", "a view of the role", "view of the role of", "of the role of specific", "the role of specific aquaporins", "role of specific aquaporins in", "of specific aquaporins in maintenance", "specific aquaporins in maintenance of", "aquaporins in maintenance of renal", "in maintenance of renal water", "maintenance of renal water balance", "renal water balance vasopressin", "water balance vasopressin regulates", "balance vasopressin regulates renal", "via aquaporins and", "aquaporins and a", "and a view of the", "of specific aquaporins in glycerol", "specific aquaporins in glycerol transport", "aquaporins in glycerol transport from", "in glycerol transport from adipocytes", "glycerol transport from adipocytes to", "transport from adipocytes to the", "to the liver transport", "the liver transport of", "liver transport of glycerol", "the liver by aquaporins ." ] }, { "record_id": "GLY_000594_1_372", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "432720", "r hsa", "hsa 432720", "r hsa 432720" ] }, { 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"human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "proton coupled", "coupled monocarboxylate", "monocarboxylate transport", "proton coupled monocarboxylate", "coupled monocarboxylate transport", "proton coupled monocarboxylate transport", "the slc16a", "slc16a gene", "gene family", "family encode", "encode proton", "proton linked", "linked monocarboxylate", "monocarboxylate transporters", "which mediate", "mediate the", "the transport", "transport of", "of monocarboxylates", "monocarboxylates such", "such as", "as lactate", "lactate and", "and pyruvate.", "pyruvate. monocarboxylates", "monocarboxylates are", "are a", "a major", "major energy", "energy source", "source for", "for all", "all cells", "cells in", "in the", "the body", "body so", "so their", "their transport", "transport in", "in and", "and out", "out of", "of cells", "cells is", "is crucial", "crucial for", "for cellular", "cellular function.", "function. to", "to date", "14 slc16a", "slc16a members", "members have", "have been", "been identified", "identified through", "through sequence", "sequence homology.", "homology. of", "of these", "these 14", "14 members", "only seven", "seven isoforms", "isoforms have", "been functionally", "functionally characterized", "characterized and", "and not", "not all", "all of", "these function", "function as", "as proton", "coupled transporters.", "transporters. a", "a number", "number can", "can transport", "transport diuretics", "thyroid hormones", "hormones and", "and aromatic", "aromatic amino", "amino acids.", "acids. the", "the seven", "seven remaining", "remaining slc16a", "members are", "are classed", "classed as", "as orphan", "orphan mcts", "morris &", "& felmlee", "felmlee 2008", "merezhinskaya &", "& fishbein", "fishbein 2009", "2009 .

in", ".

in mammalian", "mammalian cells", "require association", "association with", "with an", "an ancillary", "ancillary protein", "protein to", "to enable", "enable plasma", "plasma membrane", "membrane expression", "expression of", "of the", "the active", "active transporter.", "transporter. basigin", "is the", "the preferred", "preferred binding", "binding partner", "partner for", "for mct1", "mct3 and", "and mct4", "while mct2", "mct2 requires", "requires embigin", "wilson et", "et al.", "al. 2005", "2005 .", "the slc16a gene", "slc16a gene family", "gene family encode", "family encode proton", "encode proton linked", "proton linked monocarboxylate", "linked monocarboxylate transporters", "transporters mct", "mct which", "which mediate the", "mediate the transport", "the transport of", "transport of monocarboxylates", "of monocarboxylates such", "monocarboxylates such as", "such as lactate", "as lactate and", "lactate and pyruvate.", "and pyruvate. monocarboxylates", "pyruvate. monocarboxylates are", "monocarboxylates are a", "are a major", "a major energy", "major energy source", "energy source for", "source for all", "for all cells", "all cells in", "cells in the", "in the body", "the body so", "body so their", "so their transport", "their transport in", "transport in and", "in and out", "and out of", "out of cells", "of cells is", "cells is crucial", "is crucial for", "crucial for cellular", "for cellular function.", "cellular function. to", "function. to date", "date 14", "14 slc16a members", "slc16a members have", "members have been", "have been identified", "been identified through", "identified through sequence", "through sequence homology.", "sequence homology. of", "homology. of these", "of these 14", "these 14 members", "members only", "only seven isoforms", "seven isoforms have", "isoforms have been", "have been functionally", "been functionally characterized", "functionally characterized and", "characterized and not", "and not all", "not all of", "all of these", "of these function", "these function as", "function as proton", "as proton coupled", "proton coupled transporters.", "coupled transporters. a", "transporters. a number", "a number can", "number can transport", "can transport diuretics", "diuretics thyroid", "thyroid hormones and", "hormones and aromatic", "and aromatic amino", "aromatic amino acids.", "amino acids. the", "acids. the seven", "the seven remaining", "seven remaining slc16a", "remaining slc16a members", "slc16a members are", "members are classed", "are classed as", "classed as orphan", "as orphan mcts", "mcts morris", "morris & felmlee", "& felmlee 2008", "2008 merezhinskaya", "merezhinskaya & fishbein", "& fishbein 2009", "fishbein 2009 .

in", "2009 .

in mammalian", ".

in mammalian cells", "cells mcts", "mcts monocarboxylate", "transporters require", "require association with", "association with an", "with an ancillary", "an ancillary protein", "ancillary protein to", "protein to enable", "to enable plasma", "enable plasma membrane", "plasma membrane expression", "membrane expression of", "expression of the", "of the active", "the active transporter.", "active transporter. basigin", "basigin bsg", "bsg cd147", "cd147 is", "is the preferred", "the preferred binding", "preferred binding partner", "binding partner for", "partner for mct1", "mct1 mct3", "mct3 and mct4", "mct4 while", "while mct2 requires", "mct2 requires embigin", "embigin emb", "wilson et al.", "et al. 2005", "al. 2005 .", "the slc16a gene family", "slc16a gene family encode", "gene family encode proton", "family encode proton linked", "encode proton linked monocarboxylate", "proton linked monocarboxylate transporters", "monocarboxylate transporters mct", "mct which mediate", "which mediate the transport", "mediate the transport of", "the transport of monocarboxylates", "transport of monocarboxylates such", "of monocarboxylates such as", "monocarboxylates such as lactate", "such as lactate and", "as lactate and pyruvate.", "lactate and pyruvate. monocarboxylates", "and pyruvate. monocarboxylates are", "pyruvate. monocarboxylates are a", "monocarboxylates are a major", "are a major energy", "a major energy source", "major energy source for", "energy source for all", "source for all cells", "for all cells in", "all cells in the", "cells in the body", "in the body so", "the body so their", "body so their transport", "so their transport in", "their transport in and", "transport in and out", "in and out of", "and out of cells", "out of cells is", "of cells is crucial", "cells is crucial for", "is crucial for cellular", "crucial for cellular function.", "for cellular function. to", "cellular function. to date", "to date 14", "date 14 slc16a", "14 slc16a members have", "slc16a members have been", "members have been identified", "have been identified through", "been identified through sequence", "identified through sequence homology.", "through sequence homology. of", "sequence homology. of these", "homology. of these 14", "of these 14 members", "14 members only", "members only seven", "only seven isoforms have", "seven isoforms have been", "isoforms have been functionally", "have been functionally characterized", "been functionally characterized and", "functionally characterized and not", "characterized and not all", "and not all of", "not all of these", "all of these function", "of these function as", "these function as proton", "function as proton coupled", "as proton coupled transporters.", "proton coupled transporters. a", "coupled transporters. a number", "transporters. a number can", "a number can transport", "number can transport diuretics", "transport diuretics thyroid", "diuretics thyroid hormones", "thyroid hormones and aromatic", "hormones and aromatic amino", "and aromatic amino acids.", "aromatic amino acids. the", "amino acids. the seven", "acids. the seven remaining", "the seven remaining slc16a", "seven remaining slc16a members", "remaining slc16a members are", "slc16a members are classed", "members are classed as", "are classed as orphan", "classed as orphan mcts", "orphan mcts morris", "mcts morris &", "morris & felmlee 2008", "felmlee 2008 merezhinskaya", "2008 merezhinskaya &", "merezhinskaya & fishbein 2009", "& fishbein 2009 .

in", "fishbein 2009 .

in mammalian", "2009 .

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in", "& fishbein 2009 .

in mammalian", "fishbein 2009 .

in mammalian cells", ".

in mammalian cells mcts", "cells mcts monocarboxylate", "monocarboxylate transporters require association", "transporters require association with", "require association with an ancillary", "association with an ancillary protein", "with an ancillary protein to", "an ancillary protein to enable", "ancillary protein to enable plasma", "protein to enable plasma membrane", "to enable plasma membrane expression", "enable plasma membrane expression of", "plasma membrane expression of the", "membrane expression of the active", "expression of the active transporter.", "of the active transporter. basigin", "active transporter. basigin bsg", "basigin bsg cd147", "bsg cd147 is", "cd147 is the preferred", "is the preferred binding partner", "the preferred binding partner for", "preferred binding partner for mct1", "partner for mct1 mct3", "for mct1 mct3 and", "mct1 mct3 and mct4", "mct3 and mct4 while", "and mct4 while mct2", "mct4 while mct2 requires", "mct2 requires embigin emb", "emb wilson et", "wilson et al. 2005 ." ] }, { "record_id": "GLY_000594_1_375", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "434316", "r hsa", "hsa 434316", "r hsa 434316" ] }, { "record_id": "GLY_000594_1_375", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fatty acids", "acids bound", "bound to", "to gpr40", "regulate insulin", "insulin secretion", "fatty acids bound", "acids bound to", "bound to gpr40", "gpr40 ffar1", "ffar1 regulate", "regulate insulin secretion", "fatty acids bound to", "acids bound to gpr40", "to gpr40 ffar1", "ffar1 regulate insulin", "fatty acids bound to gpr40", "bound to gpr40 ffar1", "gpr40 ffar1 regulate", "ffar1 regulate insulin secretion", "acids augment", "augment the", "the glucose", "glucose triggered", "triggered secretion", "secretion of", "of insulin", "insulin through", "through two", "two mechanisms:", "mechanisms: intracellular", "intracellular metabolism", 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"f actin flow with extracellular", "actin flow with extracellular immobile", "flow with extracellular immobile ligands.
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forward translocation", "extracellular immobile ligands.
forward translocation of", "immobile ligands.
forward translocation of growth", "ligands.
forward translocation of growth cone", "translocation of growth cone requires", "of growth cone requires not", "growth cone requires not only", "cone requires not only the", "requires not only the cam", "not only the cam actin", "only the cam actin linkage", "the cam actin linkage but", "cam actin linkage but also", "actin linkage but also a", "linkage but also a gradient", "but also a gradient of", "also a gradient of cell", "a gradient of cell substrate", "gradient of cell substrate adhesion", "cell substrate adhesion strong", "substrate adhesion strong adhesion", "adhesion strong adhesion at", "strong adhesion at the front", "adhesion at the front and", "at the front and weak", "the front and weak adhesion", "front and weak adhesion at", "and weak adhesion at the", "weak adhesion at the rear", "at the rear so", "the rear so that", "rear so that the", "so that the cytoskeletal machinery", "that the cytoskeletal machinery is", "the cytoskeletal machinery is able", "cytoskeletal machinery is able to", "machinery is able to pull", "is able to pull the", "able to pull the cell", "to pull the cell forward", "pull the cell forward as", "the cell forward as attachments", "cell forward as attachments at", "forward as attachments at the", "as attachments at the rear", "attachments at the rear are", "at the rear are released.", "the rear are released. this", "rear are released. this asymmetry", "are released. this asymmetry is", "released. this asymmetry is achieved", "this asymmetry is achieved in", "asymmetry is achieved in part", "is achieved in part by", "achieved in part by internalizing", "in part by internalizing l1", "part by internalizing l1 molecules", "by internalizing l1 molecules as", "internalizing l1 molecules as they", "l1 molecules as they are", "molecules as they are moved", "as they are moved to", "they are moved to the", "are moved to the rear", "moved to the rear of", "to the rear of the", "the rear of the growth", "rear of the growth cone", "of the growth cone coupled", "the growth cone coupled to", "growth cone coupled to retrograde", "cone coupled to retrograde f", "coupled to retrograde f actin", "to retrograde f actin flow", "retrograde f actin flow and", "f actin flow and recycling", "actin flow and recycling them", "flow and recycling them to", "and recycling them to the", "recycling them to the leading", "them to the leading edge", "to the leading edge plasma", "the leading edge plasma membrane.
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l1 internalization", "edge plasma membrane.
l1 internalization is", "plasma membrane.
l1 internalization is mediated", "membrane.
l1 internalization is mediated by", "internalization is mediated by phosphorylation", "is mediated by phosphorylation and", "mediated by phosphorylation and dephosphorylation.", "by phosphorylation and dephosphorylation. the", "phosphorylation and dephosphorylation. the l1", "and dephosphorylation. the l1 cytoplasmic", "dephosphorylation. the l1 cytoplasmic domain", "l1 cytoplasmic domain l1cd", "domain l1cd carries", "l1cd carries an endocytic", "carries an endocytic or sorting", "an endocytic or sorting motif", "or sorting motif yrsle", "motif yrsle that", "yrsle that is recognized", "that is recognized by the", "is recognized by the clathrin", "recognized by the clathrin associated", "by the clathrin associated adaptor", "the clathrin associated adaptor protein", "clathrin associated adaptor protein 2", "adaptor protein 2 ap", "protein 2 ap 2", "2 ap 2 .", "ap 2 . ap 2", "2 . ap 2 binds", ". ap 2 binds the", "ap 2 binds the yrsle", "2 binds the yrsle motif", "binds the yrsle motif only", "the yrsle motif only when", "yrsle motif only when its", "motif only when its tyrosine", "only when its tyrosine is", "when its tyrosine is not", "its tyrosine is not phosphorylated", "tyrosine is not phosphorylated and", "is not phosphorylated and triggers", "not phosphorylated and triggers l1", "phosphorylated and triggers l1 endocytosis.", "and triggers l1 endocytosis. src", "triggers l1 endocytosis. src kinase", "l1 endocytosis. src kinase associated", "endocytosis. src kinase associated with", "src kinase associated with lipid", "kinase associated with lipid rafts", "associated with lipid rafts in", "with lipid rafts in the", "lipid rafts in the p", "rafts in the p domain", "in the p domain membrane", "the p domain membrane phosphorylates", "p domain membrane phosphorylates l1", "domain membrane phosphorylates l1 molecules", "membrane phosphorylates l1 molecules on", "phosphorylates l1 molecules on tyrosine", "l1 molecules on tyrosine 1176", "on tyrosine 1176 stabilizing", "tyrosine 1176 stabilizing them", "1176 stabilizing them in", "stabilizing them in the plasma", "them in the plasma membrane.", "in the plasma membrane. l1", "the plasma membrane. l1 endocytosis", "plasma membrane. l1 endocytosis is", "membrane. l1 endocytosis is triggered", "l1 endocytosis is triggered by", "endocytosis is triggered by the", "is triggered by the dephosphorylation", "triggered by the dephosphorylation of", "by the dephosphorylation of y1176", "the dephosphorylation of y1176 within", "dephosphorylation of y1176 within the", "of y1176 within the c", "y1176 within the c domain.", "within the c domain. some", "the c domain. some of", "c domain. some of these", "domain. some of these internalized", "some of these internalized l1", "of these internalized l1 molecules", "these internalized l1 molecules are", "internalized l1 molecules are transported", "l1 molecules are transported in", "molecules are transported in an", "are transported in an anterograde", "transported in an anterograde direction", "in an anterograde direction along", "an anterograde direction along microtubules", "anterograde direction along microtubules for", "direction along microtubules for reuse", "along microtubules for reuse in", "microtubules for reuse in the", "for reuse in the leading", "reuse in the leading edge." ] }, { "record_id": "GLY_000594_1_377", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "438066", "r hsa", "hsa 438066", "r hsa 438066" ] }, { "record_id": "GLY_000594_1_377", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "unblocking of", "of nmda", "nmda receptors", "glutamate binding", "binding and", "and activation", "unblocking of nmda", "of nmda receptors", "receptors glutamate", "glutamate binding and", "binding and activation", "unblocking of nmda receptors", "nmda receptors glutamate", "receptors glutamate binding", "glutamate binding and activation", "of nmda receptors 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free fatty acid receptor 1", "acid receptor 1 ffar1/gpr40", "1 ffar1/gpr40 is", "ffar1/gpr40 is activated by", "is activated by both saturated", "activated by both saturated and", "by both saturated and unsaturated", "both saturated and unsaturated medium", "saturated and unsaturated medium to", "and unsaturated medium to long", "unsaturated medium to long chain", "medium to long chain fatty", "to long chain fatty acids", "long chain fatty acids while", "chain fatty acids while ffar2", "acids while ffar2 gpr43", "ffar2 gpr43 and", "ffar3 gpr41 are", "gpr41 are activated by", "are activated by short chain", "activated by short chain fatty", "by short chain fatty acids", "chain fatty acids carboxylates", "acids carboxylates with", "carboxylates with six or", "with six or fewer carbon", "six or fewer carbon molecules.", "or fewer carbon molecules. a", "fewer carbon molecules. a fourth", "carbon molecules. a fourth highly", "molecules. a fourth highly homologous", "a fourth highly homologous receptor", "fourth highly homologous receptor gpr42", "highly homologous receptor gpr42 is", "homologous receptor gpr42 is believed", "receptor gpr42 is believed to", "gpr42 is believed to be", "is believed to be a", "believed to be a pseudogene", "to be a pseudogene with", "be a pseudogene with intact", "a pseudogene with intact open", "pseudogene with intact open reading", "with intact open reading frame", "open reading frame but", "reading frame but could", "frame but could be", "but could be a functional", "could be a functional gene", "be a functional gene in", "a functional gene in a", "functional gene in a significant", "gene in a significant fraction", "in a significant fraction of", "a significant fraction of the", "significant fraction of the human", "fraction of the human population.", "of the human population.

gpr120", "the human population.

gpr120 is", "human population.

gpr120 is activated", "population.

gpr120 is activated by", "

gpr120 is activated by long", "is activated by long chain", "by long chain c16", "long chain c16 22", "c16 22 fatty acids." ] }, { "record_id": "GLY_000594_1_383", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "445095", "r hsa", "hsa 445095", "r hsa 445095" ] }, { "record_id": "GLY_000594_1_383", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interaction between", "between l1", "l1 and", "and ankyrins", "interaction between l1", "between l1 and", "l1 and ankyrins", "interaction between l1 and", "between l1 and ankyrins", "interaction between l1 and ankyrins", "ankyrins are", "are a", "a family", "family of", "of adaptor", "adaptor proteins", "proteins that", "that couple", "couple membrane", "membrane proteins", "proteins such", "such as", "as voltage", "voltage gated", "gated na+", "na+ channels", "channels and", "and the", "the na+/k+", "na+/k+ anion", "anion exchanger", "exchanger to", "to the", "the spectrin", "spectrin actin", "actin cytoskeleton.", "cytoskeleton. ankyrins", "are encoded", "encoded by", "by three", "three genes", "ankyrin g", "b and", "of which", "which ankyrin", "g and", "b are", "are the", "the major", "major forms", "forms expressed", "expressed in", "in the", "the developing", "developing nervous", "nervous system.", "system. ankyrins", "ankyrins bind", "bind to", "the cytoplasmic", "cytoplasmic domain", "domain of", "of l1", "l1 cams", "cams and", "and couple", "couple them", "them and", "and ion", "ion channel", "channel proteins", "spectrin cytoskeleton.", "cytoskeleton. this", "this binding", "binding enhances", "enhances the", "the homophilic", "homophilic adhesive", "adhesive activity", "activity of", "and reduces", "reduces its", "its mobility", "mobility within", "within the", "the plasma", "plasma membrane.", "membrane. l1", "l1 interaction", "interaction with", "with ankyrin", "ankyrin mediates", "mediates branching", "branching and", "and synaptogenesis", "synaptogenesis of", "of cortical", "cortical inhibitory", "inhibitory neurons.
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neurofascin colocalizes with nrcam and", "colocalizes with nrcam and ankyring", "with nrcam and ankyring at", "nrcam and ankyring at the", "and ankyring at the nodes", "ankyring at the nodes of", "at the nodes of ranvier.", "the nodes of ranvier. neurofascin", "nodes of ranvier. neurofascin participates", "of ranvier. neurofascin participates in", "ranvier. neurofascin participates in transheterophilic", "neurofascin participates in transheterophilic adhesion", "participates in transheterophilic adhesion with", "in transheterophilic adhesion with nrcam", "transheterophilic adhesion with nrcam and", "adhesion with nrcam and stimulates", "with nrcam and stimulates neurite", "nrcam and stimulates neurite outgrowth", "and stimulates neurite outgrowth in", "stimulates neurite outgrowth in chicken", "neurite outgrowth in chicken tectal", "outgrowth in chicken tectal neurons.", "in chicken tectal neurons. the", "chicken tectal neurons. the last", "tectal neurons. the last few", "neurons. the last few amino", "the last few amino acids", "last few amino acids of", "few amino acids of neurofascin", "amino acids of neurofascin form", "acids of neurofascin form the", "of neurofascin form the pdz", "neurofascin form the pdz class", "form the pdz class i", "the pdz class i binding", "pdz class i binding motif", "i binding motif sla", "motif sla and", "sla and through these", "and through these last few", "through these last few amino", "these last few amino acids", "last few amino acids it", "few amino acids it associates", "amino acids it associates with", "acids it associates with syntenin", "it associates with syntenin 1." ] }, { "record_id": "GLY_000594_1_390", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450321", "r hsa", "hsa 450321", "r hsa 450321" ] }, { "record_id": "GLY_000594_1_390", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "c jun", "jun kinases", "phosphorylation and", "activation mediated", "mediated by", "by activated", "activated human", "human tak1", "jnk c", "c jun kinases", "kinases phosphorylation", "and activation", "activation mediated by", "mediated by activated", "by activated human", "activated human tak1", "jnk c jun", "jun kinases phosphorylation", "kinases phosphorylation and", "phosphorylation and activation", "and activation mediated", "activation mediated by activated", "mediated by activated human", "by activated human tak1", "jnk c jun kinases", "c jun kinases phosphorylation", "jun kinases phosphorylation and", "phosphorylation and activation mediated", "and activation mediated by", "activation mediated by activated human", "mediated by activated human tak1", "jun nh2", "nh2 terminal", "terminal kinases", "are an", "an evolutionarily", "evolutionarily conserved", "conserved family", "family of", "of serine/threonine", "serine/threonine protein", "protein kinases", "that belong", "belong to", "to mitogen", "mitogen activated", "activated protein", "protein kinase", "kinase family", "also known", "known as", "as stress", "stress activated", "sapks .", ". the", "the jnk", "jnk pathway", "pathway is", "is activated", "activated by", "by heat", "heat shock", "or inflammatory", "inflammatory cytokines", "or uv", "uv radiation.", "radiation.

the", "

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activation", "proliferation.

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the", "radiation.

the jnks", "

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activation of", "proliferation.

activation of jnks", "of jnks is", "jnks is mediated", "is mediated by", "by activated tak1", "activated tak1 which", "tak1 which phosphorylates", "which phosphorylates two", "phosphorylates two dual", "two dual specificity", "dual specificity enzymes", "specificity enzymes mkk4", "mkk4 mapk", "mapk kinase 4", "4 and", "and mkk7 mapk", "mkk7 mapk kinase", "mapk kinase 7", "kinase 7 .", "c jun nh2 terminal", "jun nh2 terminal kinases", "terminal kinases jnks", "jnks are an", "are an evolutionarily conserved", "an evolutionarily conserved family", "evolutionarily conserved family of", "conserved family of serine/threonine", "family of serine/threonine protein", "of serine/threonine protein kinases", "protein kinases that", "kinases that belong", "that belong to mitogen", "belong to mitogen activated", "to mitogen activated protein", "mitogen activated protein kinase", "activated protein kinase family", "kinase family mapks", "mapks also", "also known as stress", "known as stress activated", "as stress activated protein", "stress activated protein kinases", "protein kinases sapks", "kinases sapks .", "sapks . the jnk", ". the jnk pathway", "the jnk pathway is", "jnk pathway is activated", "pathway is activated by", "is activated by heat", "activated by heat shock", "heat shock or", "shock or inflammatory", "inflammatory cytokines or", "cytokines or uv", "or uv radiation.

the", "uv radiation.

the jnks", "radiation.

the jnks are", "

the jnks are encoded", "jnks are encoded by", "are encoded by at", "encoded by at least", "by at least three", "at least three genes:", "least three genes: jnk1/sapk", "three genes: jnk1/sapk gamma", "jnk1/sapk gamma jnk2/sapk", "gamma jnk2/sapk alpha", "jnk2/sapk alpha and jnk3/", "alpha and jnk3/ sapk", "and jnk3/ sapk beta.", "jnk3/ sapk beta. the", "sapk beta. the first", "beta. the first two", "the first two are", "first two are ubiquitously", "two are ubiquitously expressed", "ubiquitously expressed whereas", "expressed whereas the", "whereas the jnk3 protein", "the jnk3 protein is", "jnk3 protein is found", "protein is found mainly", "is found mainly in", "found mainly in brain", "mainly in brain and", "in brain and to", "brain and to a", "and to a lesser", "to a lesser extent", "a lesser extent in", "lesser extent in heart", "extent in heart and", "in heart and testes.", "heart and testes. as", "and testes. as a", "testes. as a result", "as a result of", "a result of alternative", "result of alternative gene", "of alternative gene splicing", "alternative gene splicing all", "gene splicing all cells", "splicing all cells express", "all cells express distinct", "cells express distinct active", "express distinct active forms", "distinct active forms of", "active forms of jnk", "forms of jnk from", "of jnk from 46", "jnk from 46 to", "from 46 to 55", "46 to 55 kda", "to 55 kda in", "55 kda in size.", "kda in size. sequence", "in size. sequence alignment", "size. sequence alignment of", "sequence alignment of these", "alignment of these different", "of these different products", "these different products shows", "different products shows homologies", "products shows homologies of", "shows homologies of >80%.", "homologies of >80%. in", "of >80%. in spite", ">80%. in spite of", "in spite of this", "spite of this similarity", "this similarity the", "similarity the multiple", "the multiple jnk isoforms", "multiple jnk isoforms differ", "jnk isoforms differ in", "isoforms differ in their", "differ in their ability", "in their ability to", "their ability to bind", "ability to bind and", "to bind and phosphorylate", "bind and phosphorylate different", "and phosphorylate different target", "phosphorylate different target proteins", "target proteins thus", "proteins thus leading", "thus leading to the", "leading to the distinctive", "to the distinctive cellular", "the distinctive cellular processes:", "distinctive cellular processes: induction", "cellular processes: induction of", "processes: induction of apoptosis", "of apoptosis or", "apoptosis or enhancment", "or enhancment of cell", "enhancment of cell survival", "cell survival or", "survival or proliferation.

activation", "or proliferation.

activation of jnks", "proliferation.

activation of jnks is", "of jnks is mediated", "jnks is mediated by", "is mediated by activated", "mediated by activated tak1", "by activated tak1 which", "activated tak1 which phosphorylates", "tak1 which phosphorylates two", "which phosphorylates two dual", "phosphorylates two dual specificity", "two dual specificity enzymes", "dual specificity enzymes mkk4", "enzymes mkk4 mapk", "mkk4 mapk kinase", "kinase 4 and", "4 and mkk7", "and mkk7 mapk kinase", "mkk7 mapk kinase 7", "mapk kinase 7 .", "c jun nh2 terminal kinases", "nh2 terminal kinases jnks", "kinases jnks are", "jnks are an evolutionarily", "are an evolutionarily conserved family", "an evolutionarily conserved family of", "evolutionarily conserved family of serine/threonine", "conserved family of serine/threonine protein", "family of serine/threonine protein kinases", "serine/threonine protein kinases that", "protein kinases that belong", "kinases that belong to", "that belong to mitogen activated", "belong to mitogen activated protein", "to mitogen activated protein kinase", "mitogen activated protein kinase family", "protein kinase family mapks", "mapks also known", "also known as stress activated", "known as stress activated protein", "as stress activated protein kinases", "activated protein kinases sapks", "protein kinases sapks .", "kinases sapks . the", "sapks . the jnk pathway", ". the jnk pathway is", "the jnk pathway is activated", "jnk pathway is activated by", "pathway is activated by heat", "is activated by heat shock", "by heat shock or", "heat shock or inflammatory", "shock or inflammatory cytokines", "or inflammatory cytokines or", "inflammatory cytokines or uv", "cytokines or uv radiation.", "or uv radiation.

the jnks", "uv radiation.

the jnks are", "radiation.

the jnks are encoded", "

the jnks are encoded by", "jnks are encoded by at", "are encoded by at least", "encoded by at least three", "by at least three genes:", "at least three genes: jnk1/sapk", "least three genes: jnk1/sapk gamma", "genes: jnk1/sapk gamma jnk2/sapk", "jnk1/sapk gamma jnk2/sapk alpha", "gamma jnk2/sapk alpha and", "jnk2/sapk alpha and jnk3/ sapk", "alpha and jnk3/ sapk beta.", "and jnk3/ sapk beta. the", "jnk3/ sapk beta. the first", "sapk beta. the first two", "beta. the first two are", "the first two are ubiquitously", "first two are ubiquitously expressed", "are ubiquitously expressed whereas", "ubiquitously expressed whereas the", "expressed whereas the jnk3", "whereas the jnk3 protein is", "the jnk3 protein is found", "jnk3 protein is found mainly", "protein is found mainly in", "is found mainly in brain", "found mainly in brain and", "mainly in brain and to", "in brain and to a", "brain and to a lesser", "and to a lesser extent", "to a lesser extent in", "a lesser extent in heart", "lesser extent in heart and", "extent in heart and testes.", "in heart and testes. as", "heart and testes. as a", "and testes. as a result", "testes. as a result of", "as a result of alternative", "a result of alternative gene", "result of alternative gene splicing", "of alternative gene splicing all", "alternative gene splicing all cells", "gene splicing all cells express", "splicing all cells express distinct", "all cells express distinct active", "cells express distinct active forms", "express distinct active forms of", "distinct active forms of jnk", "active forms of jnk from", "forms of jnk from 46", "of jnk from 46 to", "jnk from 46 to 55", "from 46 to 55 kda", "46 to 55 kda in", "to 55 kda in size.", "55 kda in size. sequence", "kda in size. sequence alignment", "in size. sequence alignment of", "size. sequence alignment of these", "sequence alignment of these different", "alignment of these different products", "of these different products shows", "these different products shows homologies", "different products shows homologies of", "products shows homologies of >80%.", "shows homologies of >80%. in", "homologies of >80%. in spite", "of >80%. in spite of", ">80%. in spite of this", "in spite of this similarity", "of this similarity the", "this similarity the multiple", "similarity the multiple jnk", "the multiple jnk isoforms differ", "multiple jnk isoforms differ in", "jnk isoforms differ in their", "isoforms differ in their ability", "differ in their ability to", "in their ability to bind", "their ability to bind and", "ability to bind and phosphorylate", "to bind and phosphorylate different", "bind and phosphorylate different target", "and phosphorylate different target proteins", "different target proteins thus", "target proteins thus leading", "proteins thus leading to", "thus leading to the distinctive", "leading to the distinctive cellular", "to the distinctive cellular processes:", "the distinctive cellular processes: induction", "distinctive cellular processes: induction of", "cellular processes: induction of apoptosis", "induction of apoptosis or", "of apoptosis or enhancment", "apoptosis or enhancment of", "or enhancment of cell survival", "of cell survival or", "cell survival or proliferation.

activation", "survival or proliferation.

activation of", "or proliferation.

activation of jnks is", "proliferation.

activation of jnks is mediated", "of jnks is mediated by", "jnks is mediated by activated", "is mediated by activated tak1", "mediated by activated tak1 which", "by activated tak1 which phosphorylates", "activated tak1 which phosphorylates two", "tak1 which phosphorylates two dual", "which phosphorylates two dual specificity", "phosphorylates two dual specificity enzymes", "two dual specificity enzymes mkk4", "specificity enzymes mkk4 mapk", "enzymes mkk4 mapk kinase", "mkk4 mapk kinase 4", "mapk kinase 4 and", "kinase 4 and mkk7", "4 and mkk7 mapk", "and mkk7 mapk kinase 7", "mkk7 mapk kinase 7 ." ] }, { "record_id": "GLY_000594_1_391", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450408", "r hsa", "hsa 450408", "r hsa 450408" ] }, { "record_id": "GLY_000594_1_391", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hnrnp d0", "binds and", "and destabilizes", "destabilizes mrna", "auf1 hnrnp", "d0 binds", "binds and destabilizes", "and destabilizes mrna", "auf1 hnrnp d0", "hnrnp d0 binds", "d0 binds and", "binds and destabilizes mrna", "hnrnp d0 binds and", "d0 binds and destabilizes", "dimers bind", "bind u", "u rich", "rich regions", "regions of", "of au", "au rich", "rich elements", "in the", "the 3'", "3' untranslated", "untranslated regions", "of mrnas.", "mrnas. the", "the binding", "binding causes", "causes auf1", "auf1 dimers", "dimers to", "to assemble", "assemble into", "into higher", "higher order", "order tetrameric", "tetrameric complexes.", "complexes. diphosphorylated", "diphosphorylated auf1", "auf1 bound", "bound to", "to rna", "rna recruits", "recruits additional", "additional proteins", "including eif4g", "polya binding", "binding protein", "nsep 1", "nsap 1", "and imp", "imp 2", "2 which", "which target", "target the", "the mrna", "mrna and", "and auf1", "auf1 for", "for degradation.", "degradation. unphosphorylated", "unphosphorylated auf1", "auf1 is", "is thought", "thought to", "to be", "be less", "less able", "able to", "to recruit", "recruit additional", "additional proteins.", "proteins. auf1", "auf1 also", "also interacts", "interacts directly", "directly or", "or indirectly", "indirectly with", "with hur", "hur and", "and the", "the rna", "rna induced", "induced silencing", "silencing complex", "risc .
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at", "unknown.
at least", "least 4", "4 isoforms", "isoforms of", "of auf1", "auf1 exist:", "exist: p45", "45 kda", "contains all", "all exons", "p42 lacks", "lacks exon", "exon 2", "p40 lacks", "exon 7", "and p37", "p37 lacks", "lacks exons", "exons 2", "2 and", "and 7.", "7. the", "the presence", "presence of", "of exon", "7 in", "in p42", "p42 and", "and p45", "p45 seems", "seems to", "to block", "block ubiquitination", "ubiquitination while", "the absence", "absence of", "p37 and", "and p40", "targets auf1", "for ubiquitination", "ubiquitination and", "destabilizes bound", "bound rnas.", "rnas. lack", "lack of", "and p42", "is associated", "associated with", "with higher", "higher affinity", "affinity for", "for rna", "and 14", "14 3", "3 3sigma", "sfn .
auf1", ".
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auf1 complexed with", "complexed with rna", "with rna and", "rna and other", "and other proteins", "other proteins is", "proteins is ubiquitinated", "is ubiquitinated and", "ubiquitinated and targeted", "and targeted for", "targeted for destruction", "for destruction by", "destruction by the", "by the proteasome", "the proteasome while", "proteasome while the", "while the bound", "the bound mrna", "bound mrna is", "mrna is degraded.", "is degraded. inhibition", "degraded. inhibition of", "inhibition of ubiquitin", "of ubiquitin addition", "ubiquitin addition to", "addition to auf1", "to auf1 blocks", "auf1 blocks mrna", "blocks mrna degradation.", "mrna degradation. the", "degradation. the mechanism", "the mechanism by", "mechanism by which", "by which ubiquitin", "which ubiquitin dependent", "ubiquitin dependent proteolysis", "dependent proteolysis is", "proteolysis is coupled", "is coupled to", "coupled to mrna", "to mrna degradation", "mrna degradation is", "degradation is unknown.
at", "is unknown.
at least", "unknown.
at least 4", "least 4 isoforms", "4 isoforms of", "isoforms of auf1", "of auf1 exist:", "auf1 exist: p45", "p45 45", "kda contains", "contains all exons", "exons p42", "p42 lacks exon", "lacks exon 2", "2 p40", "p40 lacks exon", "lacks exon 7", "7 and", "and p37 lacks", "p37 lacks exons", "lacks exons 2", "exons 2 and", "2 and 7.", "and 7. the", "7. the presence", "the presence of", "presence of exon", "of exon 7", "exon 7 in", "7 in p42", "in p42 and", "p42 and p45", "and p45 seems", "p45 seems to", "seems to block", "to block ubiquitination", "block ubiquitination while", "ubiquitination while the", "while the absence", "the absence of", "absence of exon", "7 p37", "p37 and p40", "p40 targets", "targets auf1 for", "auf1 for ubiquitination", "for ubiquitination and", "ubiquitination and destabilizes", "and destabilizes bound", "destabilizes bound rnas.", "bound rnas. lack", "rnas. lack of", "lack of exon", "of exon 2", "2 p37", "p37 and p42", "p42 is", "is associated with", "associated with higher", "with higher affinity", "higher affinity for", "affinity for rna", "for rna and", "rna and 14", "and 14 3", "14 3 3sigma", "3sigma sfn", "sfn .
auf1 binds", ".
auf1 binds and", "and destabilizes mrnas", "destabilizes mrnas encoding", "mrnas encoding interleukin", "encoding interleukin 1", "interleukin 1 beta", "beta il1b", "tumor necrosis factor", "necrosis factor alpha", "alpha tnfa", "cyclin dependent kinase", "dependent kinase inhibitor", "kinase inhibitor 1", "1 cdnk1a", "cdnk1a p21", "d1 ccnd1", "granulocyte macrophage colony", "macrophage colony stimulating", "colony stimulating factor", "factor gm", "csf csf2", "inducible nitric oxide", "nitric oxide synthase", "synthase inos", "inos nos2", "proto oncogene cfos", "cfos fos", "myc proto oncogene", "oncogene myc", "apoptosis regulator bcl", "regulator bcl 2", "2 bcl2", "hnrnp d0 dimers", "d0 dimers bind", "dimers bind u rich", "bind u rich regions", "u rich regions of", "rich regions of au", "regions of au rich", "of au rich elements", "rich elements ares", "ares in the", "in the 3' untranslated", "the 3' untranslated regions", "3' untranslated regions of", "untranslated regions of mrnas.", "regions of mrnas. the", "of mrnas. the binding", "mrnas. the binding causes", "the binding causes auf1", "binding causes auf1 dimers", "causes auf1 dimers to", "auf1 dimers to assemble", "dimers to assemble into", "to assemble into higher", "assemble into higher order", "into higher order tetrameric", "higher order tetrameric complexes.", "order tetrameric complexes. diphosphorylated", "tetrameric complexes. diphosphorylated auf1", "complexes. diphosphorylated auf1 bound", "diphosphorylated auf1 bound to", "auf1 bound to rna", "bound to rna recruits", "to rna recruits additional", "rna recruits additional proteins", "additional proteins including", "proteins including eif4g", "including eif4g polya", "eif4g polya binding", "binding protein hsp", "hsp27 nsep 1", "nsep 1 nsap", "1 nsap 1", "nsap 1 and", "1 and imp", "and imp 2 which", "imp 2 which target", "2 which target the", "which target the mrna", "target the mrna and", "the mrna and auf1", "mrna and auf1 for", "and auf1 for degradation.", "auf1 for degradation. unphosphorylated", "for degradation. unphosphorylated auf1", "degradation. unphosphorylated auf1 is", "unphosphorylated auf1 is thought", "auf1 is thought to", "is thought to be", "thought to be less", "to be less able", "be less able to", "less able to recruit", "able to recruit additional", "to recruit additional proteins.", "recruit additional proteins. auf1", "additional proteins. auf1 also", "proteins. auf1 also interacts", "auf1 also interacts directly", "also interacts directly or", "interacts directly or indirectly", "directly or indirectly with", "or indirectly with hur", "indirectly with hur and", "with hur and the", "hur and the rna", "and the rna induced", "the rna induced silencing", "rna induced silencing complex", "silencing complex risc", "complex risc .
auf1", "risc .
auf1 complexed with", ".
auf1 complexed with rna", "complexed with rna and", "with rna and other", "rna and other proteins", "and other proteins is", "other proteins is ubiquitinated", "proteins is ubiquitinated and", "is ubiquitinated and targeted", "ubiquitinated and targeted for", "and targeted for destruction", "targeted for destruction by", "for destruction by the", "destruction by the proteasome", "by the proteasome while", "the proteasome while the", "proteasome while the bound", "while the bound mrna", "the bound mrna is", "bound mrna is degraded.", "mrna is degraded. inhibition", "is degraded. inhibition of", "degraded. inhibition of ubiquitin", "inhibition of ubiquitin addition", "of ubiquitin addition to", "ubiquitin addition to auf1", "addition to auf1 blocks", "to auf1 blocks mrna", "auf1 blocks mrna degradation.", "blocks mrna degradation. the", "mrna degradation. the mechanism", "degradation. the mechanism by", "the mechanism by which", "mechanism by which ubiquitin", "by which ubiquitin dependent", "which ubiquitin dependent proteolysis", "ubiquitin dependent proteolysis is", "dependent proteolysis is coupled", "proteolysis is coupled to", "is coupled to mrna", "coupled to mrna degradation", "to mrna degradation is", "mrna degradation is unknown.
at", "degradation is unknown.
at least", "is unknown.
at least 4", "unknown.
at least 4 isoforms", "least 4 isoforms of", "4 isoforms of auf1", "isoforms of auf1 exist:", "of auf1 exist: p45", "exist: p45 45", "p45 45 kda", "45 kda contains", "kda contains all", "all exons p42", "exons p42 lacks", "p42 lacks exon 2", "exon 2 p40", "2 p40 lacks", "p40 lacks exon 7", "exon 7 and", "7 and p37", "and p37 lacks exons", "p37 lacks exons 2", "lacks exons 2 and", "exons 2 and 7.", "2 and 7. the", "and 7. the presence", "7. the presence of", "the presence of exon", "presence of exon 7", "of exon 7 in", "exon 7 in p42", "7 in p42 and", "in p42 and p45", "p42 and p45 seems", "and p45 seems to", "p45 seems to block", "seems to block ubiquitination", "to block ubiquitination while", "block ubiquitination while the", "ubiquitination while the absence", "while the absence of", "the absence of exon", "absence of exon 7", "exon 7 p37", "7 p37 and", "and p40 targets", "p40 targets auf1", "targets auf1 for ubiquitination", "auf1 for ubiquitination and", "for ubiquitination and destabilizes", "ubiquitination and destabilizes bound", "and destabilizes bound rnas.", "destabilizes bound rnas. lack", "bound rnas. lack of", "rnas. lack of exon", "lack of exon 2", "exon 2 p37", "2 p37 and", "and p42 is", "p42 is associated", "is associated with higher", "associated with higher affinity", "with higher affinity for", "higher affinity for rna", "affinity for rna and", "for rna and 14", "rna and 14 3", "and 14 3 3sigma", "3 3sigma sfn", "3sigma sfn .
auf1", "sfn .
auf1 binds and", ".
auf1 binds and destabilizes", "binds and destabilizes mrnas", "and destabilizes mrnas encoding", "destabilizes mrnas encoding interleukin", "mrnas encoding interleukin 1", "encoding interleukin 1 beta", "1 beta il1b", "il1b tumor", "tumor necrosis factor alpha", "factor alpha tnfa", "tnfa cyclin", "cyclin dependent kinase inhibitor", "dependent kinase inhibitor 1", "inhibitor 1 cdnk1a", "p21 cyclin", "cyclin d1 ccnd1", "ccnd1 granulocyte", "granulocyte macrophage colony stimulating", "macrophage colony stimulating factor", "stimulating factor gm", "factor gm csf", "gm csf csf2", "csf2 inducible", "inducible nitric oxide synthase", "oxide synthase inos", "nos2 proto", "oncogene cfos fos", "fos myc", "proto oncogene myc", "myc apoptosis", "apoptosis regulator bcl 2", "bcl 2 bcl2", "2 bcl2 .", "hnrnp d0 dimers bind", "d0 dimers bind u", "dimers bind u rich regions", "bind u rich regions of", "u rich regions of au", "rich regions of au rich", "regions of au rich elements", "au rich elements ares", "elements ares in", "ares in the 3'", "in the 3' untranslated regions", "the 3' untranslated regions of", "3' untranslated regions of mrnas.", "untranslated regions of mrnas. the", "regions of mrnas. the binding", "of mrnas. the binding causes", "mrnas. the binding causes auf1", "the binding causes auf1 dimers", "binding causes auf1 dimers to", "causes auf1 dimers to assemble", "auf1 dimers to assemble into", "dimers to assemble into higher", "to assemble into higher order", "assemble into higher order tetrameric", "into higher order tetrameric complexes.", "higher order tetrameric complexes. diphosphorylated", "order tetrameric complexes. diphosphorylated auf1", "tetrameric complexes. diphosphorylated auf1 bound", "complexes. diphosphorylated auf1 bound to", "diphosphorylated auf1 bound to rna", "auf1 bound to rna recruits", "bound to rna recruits additional", "to rna recruits additional proteins", "recruits additional proteins including", "additional proteins including eif4g", "including eif4g polya binding", "eif4g polya binding protein", "polya binding protein hsp", "protein hsp hsc70", "hsp hsc70 hsp27", "hsc70 hsp27 nsep", "nsep 1 nsap 1", "nsap 1 and imp", "1 and imp 2", "and imp 2 which target", "imp 2 which target the", "2 which target the mrna", "which target the mrna and", "target the mrna and auf1", "the mrna and auf1 for", "mrna and auf1 for degradation.", "and auf1 for degradation. unphosphorylated", "auf1 for degradation. unphosphorylated auf1", "for degradation. unphosphorylated auf1 is", "degradation. unphosphorylated auf1 is thought", "unphosphorylated auf1 is thought to", "auf1 is thought to be", "is thought to be less", "thought to be less able", "to be less able to", "be less able to recruit", "less able to recruit additional", "able to recruit additional proteins.", "to recruit additional proteins. auf1", "recruit additional proteins. auf1 also", "additional proteins. auf1 also interacts", "proteins. auf1 also interacts directly", "auf1 also interacts directly or", "also interacts directly or indirectly", "interacts directly or indirectly with", "directly or indirectly with hur", "or indirectly with hur and", "indirectly with hur and the", "with hur and the rna", "hur and the rna induced", "and the rna induced silencing", "the rna induced silencing complex", "induced silencing complex risc", "silencing complex risc .
auf1", "complex risc .
auf1 complexed", "risc .
auf1 complexed with rna", ".
auf1 complexed with rna and", "complexed with rna and other", "with rna and other proteins", "rna and other proteins is", "and other proteins is ubiquitinated", "other proteins is ubiquitinated and", "proteins is ubiquitinated and targeted", "is ubiquitinated and targeted for", "ubiquitinated and targeted for destruction", "and targeted for destruction by", "targeted for destruction by the", "for destruction by the proteasome", "destruction by the proteasome while", "by the proteasome while the", "the proteasome while the bound", "proteasome while the bound mrna", "while the bound mrna is", "the bound mrna is degraded.", "bound mrna is degraded. inhibition", "mrna is degraded. inhibition of", "is degraded. inhibition of ubiquitin", "degraded. inhibition of ubiquitin addition", "inhibition of ubiquitin addition to", "of ubiquitin addition to auf1", "ubiquitin addition to auf1 blocks", "addition to auf1 blocks mrna", "to auf1 blocks mrna degradation.", "auf1 blocks mrna degradation. the", "blocks mrna degradation. the mechanism", "mrna degradation. the mechanism by", "degradation. the mechanism by which", "the mechanism by which ubiquitin", "mechanism by which ubiquitin dependent", "by which ubiquitin dependent proteolysis", "which ubiquitin dependent proteolysis is", "ubiquitin dependent proteolysis is coupled", "dependent proteolysis is coupled to", "proteolysis is coupled to mrna", "is coupled to mrna degradation", "coupled to mrna degradation is", "to mrna degradation is unknown.
at", "mrna degradation is unknown.
at least", "degradation is unknown.
at least 4", "is unknown.
at least 4 isoforms", "unknown.
at least 4 isoforms of", "least 4 isoforms of auf1", "4 isoforms of auf1 exist:", "isoforms of auf1 exist: p45", "auf1 exist: p45 45", "exist: p45 45 kda", "45 kda contains all", "kda contains all exons", "contains all exons p42", "all exons p42 lacks", "exons p42 lacks exon", "lacks exon 2 p40", "exon 2 p40 lacks", "2 p40 lacks exon", "lacks exon 7 and", "exon 7 and p37", "7 and p37 lacks", "and p37 lacks exons 2", "p37 lacks exons 2 and", "lacks exons 2 and 7.", "exons 2 and 7. the", "2 and 7. the presence", "and 7. the presence of", "7. the presence of exon", "the presence of exon 7", "presence of exon 7 in", "of exon 7 in p42", "exon 7 in p42 and", "7 in p42 and p45", "in p42 and p45 seems", "p42 and p45 seems to", "and p45 seems to block", "p45 seems to block ubiquitination", "seems to block ubiquitination while", "to block ubiquitination while the", "block ubiquitination while the absence", "ubiquitination while the absence of", "while the absence of exon", "the absence of exon 7", "of exon 7 p37", "exon 7 p37 and", "7 p37 and p40", "p37 and p40 targets", "and p40 targets auf1", "p40 targets auf1 for", "targets auf1 for ubiquitination and", "auf1 for ubiquitination and destabilizes", "for ubiquitination and destabilizes bound", "ubiquitination and destabilizes bound rnas.", "and destabilizes bound rnas. lack", "destabilizes bound rnas. lack of", "bound rnas. lack of exon", "rnas. lack of exon 2", "of exon 2 p37", "exon 2 p37 and", "2 p37 and p42", "p37 and p42 is", "and p42 is associated", "p42 is associated with", "is associated with higher affinity", "associated with higher affinity for", "with higher affinity for rna", "higher affinity for rna and", "affinity for rna and 14", "for rna and 14 3", "rna and 14 3 3sigma", "14 3 3sigma sfn", "3 3sigma sfn .
auf1", "3sigma sfn .
auf1 binds", "sfn .
auf1 binds and destabilizes", ".
auf1 binds and destabilizes mrnas", "binds and destabilizes mrnas encoding", "and destabilizes mrnas encoding interleukin", "destabilizes mrnas encoding interleukin 1", "mrnas encoding interleukin 1 beta", "interleukin 1 beta il1b", "il1b tumor necrosis", "necrosis factor alpha tnfa", "tnfa cyclin dependent", "cyclin dependent kinase inhibitor 1", "kinase inhibitor 1 cdnk1a", "1 cdnk1a p21", "p21 cyclin d1", "ccnd1 granulocyte macrophage", "granulocyte macrophage colony stimulating factor", "colony stimulating factor gm", "stimulating factor gm csf", "csf2 inducible nitric", "nitric oxide synthase inos", "synthase inos nos2", "nos2 proto oncogene", "proto oncogene cfos fos", "fos myc proto", "myc proto oncogene myc", "myc apoptosis regulator", "regulator bcl 2 bcl2", "bcl 2 bcl2 ." ] }, { "record_id": "GLY_000594_1_392", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450520", "r hsa", "hsa 450520", "r hsa 450520" ] }, { "record_id": "GLY_000594_1_392", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "binds and", "and stabilizes", "stabilizes mrna", "hur elavl1", "elavl1 binds", "binds and stabilizes", "and stabilizes mrna", "elavl1 binds and", "binds and stabilizes mrna", "hur elavl1 binds", "elavl1 binds and stabilizes", "is a", "a ubiquitous", "ubiquitous protein", "protein that", "that binds", "binds au", "au rich", "rich elements", "elements in", "in mrnas", "mrnas and", "and acts", "acts to", "to stabilize", "stabilize the", "the mrnas.", "mrnas. hur", "hur activity", "activity is", "is controlled", "controlled by", "by phosphorylation", "with pkc", "pkc alpha", "alpha and", "and pck", "pck delta", "delta enhancing", "enhancing the", "the ability", "ability of", "of hur", "hur to", "to bind", "bind and", "and stabilize", "stabilize mrnas.", "mrnas. binding", "binding of", "of mrnas", "mrnas occurs", "occurs in", "in the", "the nucleus", "nucleus and", "and hur", "hur then", "then interacts", "interacts with", "with the", "the crm1", "crm1 export", "export pathway", "pathway to", "to transfer", "transfer the", "the mrna", "mrna to", "to the", "the cytoplasm.", "cytoplasm. the", "the mechanism", "mechanism by", "by which", "which hur", "hur shields", "shields the", "mrna from", "from degradation", "degradation is", "is unknown.
hur", "unknown.
hur also", "also regulates", "regulates translation", "translation of", "of some", "some mrnas", "in some", "some cases", "cases repressing", "repressing translation", "translation and", "and in", "cases enhancing", "enhancing translation", "of bound", "bound mrnas", "mrnas by", "by recruiting", "recruiting them", "them to", "to polysomes.
hur", "polysomes.
hur binds", "and regulates", "regulates mrnas", "mrnas encoding", "encoding cyclooxygenase", "cyclooxygenase 2", "cyclin a", "cyclin d1", "cyclin b1", "cd83 antigen", "and proto", "proto oncogene", "oncogene c", "c fos", "fos .
hur", ".
hur is", "a member", "member of", "of a", "a family", "family of", "of proteins", "proteins that", "that also", "also contains", "contains hud", "and huc", "elavl3 .", ". hub", "and hud", "hud are", "are specifically", "specifically expressed", "expressed in", "in neural", "neural tissue.
hur", "tissue.
hur participates", "participates in", "in apoptosis.", "apoptosis. during", "during lethal", "lethal stress", "stress hur", "hur becomes", "becomes mostly", "mostly cytoplasmic", "cytoplasmic and", "and is", "a target", "target of", "of caspase", "caspase 3", "3 and", "and caspase", "caspase 7.", "7. the", "the cleavage", "cleavage products", "products of", "hur in", "in turn", "turn promote", "promote apoptosis.", "elavl1 is", "is a ubiquitous", "a ubiquitous protein", "ubiquitous protein that", "protein that binds", "that binds au", "binds au rich", "au rich elements", "rich elements in", "elements in mrnas", "in mrnas and", "mrnas and acts", "and acts to", "acts to stabilize", "to stabilize the", "stabilize the mrnas.", "the mrnas. hur", "mrnas. hur activity", "hur activity is", "activity is controlled", "is controlled by", "controlled by phosphorylation", "phosphorylation with", "with pkc alpha", "pkc alpha and", "alpha and pck", "and pck delta", "pck delta enhancing", "delta enhancing the", "enhancing the ability", "the ability of", "ability of hur", "of hur to", "hur to bind", "to bind and", "bind and stabilize", "and stabilize mrnas.", "stabilize mrnas. binding", "mrnas. binding of", "binding of mrnas", "of mrnas occurs", "mrnas occurs in", "occurs in the", "in the nucleus", "the nucleus and", "nucleus and hur", "and hur then", "hur then interacts", "then interacts with", "interacts with the", "with the crm1", "the crm1 export", "crm1 export pathway", "export pathway to", "pathway to transfer", "to transfer the", "transfer the mrna", "the mrna to", "mrna to the", "to the cytoplasm.", "the cytoplasm. the", "cytoplasm. the mechanism", "the mechanism by", "mechanism by which", "by which hur", "which hur shields", "hur shields the", "shields the mrna", "the mrna from", "mrna from degradation", "from degradation is", "degradation is unknown.
hur", "is unknown.
hur also", "unknown.
hur also regulates", "also regulates translation", "regulates translation of", "translation of some", "of some mrnas", "mrnas in", "in some cases", "some cases repressing", "cases repressing translation", "repressing translation and", "translation and in", "and in some", "some cases enhancing", "cases enhancing translation", "enhancing translation of", "translation of bound", "of bound mrnas", "bound mrnas by", "mrnas by recruiting", "by recruiting them", "recruiting them to", "them to polysomes.
hur", "to polysomes.
hur binds", "polysomes.
hur binds and", "binds and regulates", "and regulates mrnas", "regulates mrnas encoding", "mrnas encoding cyclooxygenase", "encoding cyclooxygenase 2", "2 cox2", "cox2 ptgs2", "a ccna", "ccna ccna2", "d1 ccnd1", "b1 ccnb1", "antigen cd83", "and proto oncogene", "proto oncogene c", "oncogene c fos", "fos fos", "fos .
hur is", ".
hur is a", "is a member", "a member of", "member of a", "of a family", "a family of", "family of proteins", "of proteins that", "proteins that also", "that also contains", "also contains hud", "hud elavl4", "hub elavl2", "huc elavl3", "elavl3 . hub", "hub huc", "huc and", "and hud are", "hud are specifically", "are specifically expressed", "specifically expressed in", "expressed in neural", "in neural tissue.
hur", "neural tissue.
hur participates", "tissue.
hur participates in", "participates in apoptosis.", "in apoptosis. during", "apoptosis. during lethal", "during lethal stress", "lethal stress hur", "stress hur becomes", "hur becomes mostly", "becomes mostly cytoplasmic", "mostly cytoplasmic and", "cytoplasmic and is", "and is a", "is a target", "a target of", "target of caspase", "of caspase 3", "caspase 3 and", "3 and caspase", "and caspase 7.", "caspase 7. the", "7. the cleavage", "the cleavage products", "cleavage products of", "products of hur", "of hur in", "hur in turn", "in turn promote", "turn promote apoptosis.", "elavl1 is a", "is a ubiquitous protein", "a ubiquitous protein that", "ubiquitous protein that binds", "protein that binds au", "that binds au rich", "binds au rich elements", "au rich elements in", "rich elements in mrnas", "elements in mrnas and", "in mrnas and acts", "mrnas and acts to", "and acts to stabilize", "acts to stabilize the", "to stabilize the mrnas.", "stabilize the mrnas. hur", "the mrnas. hur activity", "mrnas. hur activity is", "hur activity is controlled", "activity is controlled by", "is controlled by phosphorylation", "by phosphorylation with", "phosphorylation with pkc", "with pkc alpha and", "pkc alpha and pck", "alpha and pck delta", "and pck delta enhancing", "pck delta enhancing the", "delta enhancing the ability", "enhancing the ability of", "the ability of hur", "ability of hur to", "of hur to bind", "hur to bind and", "to bind and stabilize", "bind and stabilize mrnas.", "and stabilize mrnas. binding", "stabilize mrnas. binding of", "mrnas. binding of mrnas", "binding of mrnas occurs", "of mrnas occurs in", "mrnas occurs in the", "occurs in the nucleus", "in the nucleus and", "the nucleus and hur", "nucleus and hur then", "and hur then interacts", "hur then interacts with", "then interacts with the", "interacts with the crm1", "with the crm1 export", "the crm1 export pathway", "crm1 export pathway to", "export pathway to transfer", "pathway to transfer the", "to transfer the mrna", "transfer the mrna to", "the mrna to the", "mrna to the cytoplasm.", "to the cytoplasm. the", "the cytoplasm. the mechanism", "cytoplasm. the mechanism by", "the mechanism by which", "mechanism by which hur", "by which hur shields", "which hur shields the", "hur shields the mrna", "shields the mrna from", "the mrna from degradation", "mrna from degradation is", "from degradation is unknown.
hur", "degradation is unknown.
hur also", "is unknown.
hur also regulates", "unknown.
hur also regulates translation", "also regulates translation of", "regulates translation of some", "translation of some mrnas", "some mrnas in", "mrnas in some", "in some cases repressing", "some cases repressing translation", "cases repressing translation and", "repressing translation and in", "translation and in some", "and in some cases", "in some cases enhancing", "some cases enhancing translation", "cases enhancing translation of", "enhancing translation of bound", "translation of bound mrnas", "of bound mrnas by", "bound mrnas by recruiting", "mrnas by recruiting them", "by recruiting them to", "recruiting them to polysomes.
hur", "them to polysomes.
hur binds", "to polysomes.
hur binds and", "polysomes.
hur binds and regulates", "binds and regulates mrnas", "and regulates mrnas encoding", "regulates mrnas encoding cyclooxygenase", "mrnas encoding cyclooxygenase 2", "cyclooxygenase 2 cox2", "ptgs2 cyclin", "cyclin a ccna", "ccna2 cyclin", "cyclin d1 ccnd1", "ccnd1 cyclin", "cyclin b1 ccnb1", "ccnb1 cd83", "cd83 antigen cd83", "cd83 and", "and proto oncogene c", "proto oncogene c fos", "c fos fos", "fos fos .
hur", "fos .
hur is a", ".
hur is a member", "is a member of", "a member of a", "member of a family", "of a family of", "a family of proteins", "family of proteins that", "of proteins that also", "proteins that also contains", "that also contains hud", "contains hud elavl4", "elavl4 hub", "elavl2 and", "and huc elavl3", "huc elavl3 .", ". hub huc", "huc and hud", "and hud are specifically", "hud are specifically expressed", "are specifically expressed in", "specifically expressed in neural", "expressed in neural tissue.
hur", "in neural tissue.
hur participates", "neural tissue.
hur participates in", "tissue.
hur participates in apoptosis.", "participates in apoptosis. during", "in apoptosis. during lethal", "apoptosis. during lethal stress", "during lethal stress hur", "lethal stress hur becomes", "stress hur becomes mostly", "hur becomes mostly cytoplasmic", "becomes mostly cytoplasmic and", "mostly cytoplasmic and is", "cytoplasmic and is a", "and is a target", "is a target of", "a target of caspase", "target of caspase 3", "of caspase 3 and", "caspase 3 and caspase", "3 and caspase 7.", "and caspase 7. the", "caspase 7. the cleavage", "7. the cleavage products", "the cleavage products of", "cleavage products of hur", "products of hur in", "of hur in turn", "hur in turn promote", "in turn promote apoptosis.", "hur elavl1 is", "elavl1 is a ubiquitous", "is a ubiquitous protein that", "a ubiquitous protein that binds", "ubiquitous protein that binds au", "protein that binds au rich", "that binds au rich elements", "binds au rich elements in", "au rich elements in mrnas", "rich elements in mrnas and", "elements in mrnas and acts", "in mrnas and acts to", "mrnas and acts to stabilize", "and acts to stabilize the", "acts to stabilize the mrnas.", "to stabilize the mrnas. hur", "stabilize the mrnas. hur activity", "the mrnas. hur activity is", "mrnas. hur activity is controlled", "hur activity is controlled by", "activity is controlled by phosphorylation", "controlled by phosphorylation with", "by phosphorylation with pkc", "phosphorylation with pkc alpha", "with pkc alpha and pck", "pkc alpha and pck delta", "alpha and pck delta enhancing", "and pck delta enhancing the", "pck delta enhancing the ability", "delta enhancing the ability of", "enhancing the ability of hur", "the ability of hur to", "ability of hur to bind", "of hur to bind and", "hur to bind and stabilize", "to bind and stabilize mrnas.", "bind and stabilize mrnas. binding", "and stabilize mrnas. binding of", "stabilize mrnas. binding of mrnas", "mrnas. binding of mrnas occurs", "binding of mrnas occurs in", "of mrnas occurs in the", "mrnas occurs in the nucleus", "occurs in the nucleus and", "in the nucleus and hur", "the nucleus and hur then", "nucleus and hur then interacts", "and hur then interacts with", "hur then interacts with the", "then interacts with the crm1", "interacts with the crm1 export", "with the crm1 export pathway", "the crm1 export pathway to", "crm1 export pathway to transfer", "export pathway to transfer the", "pathway to transfer the mrna", "to transfer the mrna to", "transfer the mrna to the", "the mrna to the cytoplasm.", "mrna to the cytoplasm. the", "to the cytoplasm. the mechanism", "the cytoplasm. the mechanism by", "cytoplasm. the mechanism by which", "the mechanism by which hur", "mechanism by which hur shields", "by which hur shields the", "which hur shields the mrna", "hur shields the mrna from", "shields the mrna from degradation", "the mrna from degradation is", "mrna from degradation is unknown.
hur", "from degradation is unknown.
hur also", "degradation is unknown.
hur also regulates", "is unknown.
hur also regulates translation", "unknown.
hur also regulates translation of", "also regulates translation of some", "regulates translation of some mrnas", "of some mrnas in", "some mrnas in some", "mrnas in some cases", "in some cases repressing translation", "some cases repressing translation and", "cases repressing translation and in", "repressing translation and in some", "translation and in some cases", "and in some cases enhancing", "in some cases enhancing translation", "some cases enhancing translation of", "cases enhancing translation of bound", "enhancing translation of bound mrnas", "translation of bound mrnas by", "of bound mrnas by recruiting", "bound mrnas by recruiting them", "mrnas by recruiting them to", "by recruiting them to polysomes.
hur", "recruiting them to polysomes.
hur binds", "them to polysomes.
hur binds and", "to polysomes.
hur binds and regulates", "polysomes.
hur binds and regulates mrnas", "binds and regulates mrnas encoding", "and regulates mrnas encoding cyclooxygenase", "regulates mrnas encoding cyclooxygenase 2", "encoding cyclooxygenase 2 cox2", "2 cox2 ptgs2", "ptgs2 cyclin a", "a ccna ccna2", "ccna2 cyclin d1", "ccnd1 cyclin b1", "ccnb1 cd83 antigen", "cd83 and proto", "and proto oncogene c fos", "oncogene c fos fos", "c fos fos .
hur", "fos fos .
hur is", "fos .
hur is a member", ".
hur is a member of", "is a member of a", "a member of a family", "member of a family of", "of a family of proteins", "a family of proteins that", "family of proteins that also", "of proteins that also contains", "proteins that also contains hud", "also contains hud elavl4", "elavl2 and huc", "and huc elavl3 .", "huc elavl3 . hub", "elavl3 . hub huc", "hub huc and", "huc and hud are", "and hud are specifically expressed", "hud are specifically expressed in", "are specifically expressed in neural", "specifically expressed in neural tissue.
hur", "expressed in neural tissue.
hur participates", "in neural tissue.
hur participates in", "neural tissue.
hur participates in apoptosis.", "tissue.
hur participates in apoptosis. during", "participates in apoptosis. during lethal", "in apoptosis. during lethal stress", "apoptosis. during lethal stress hur", "during lethal stress hur becomes", "lethal stress hur becomes mostly", "stress hur becomes mostly cytoplasmic", "hur becomes mostly cytoplasmic and", "becomes mostly cytoplasmic and is", "mostly cytoplasmic and is a", "cytoplasmic and is a target", "and is a target of", "is a target of caspase", "a target of caspase 3", "target of caspase 3 and", "of caspase 3 and caspase", "caspase 3 and caspase 7.", "3 and caspase 7. the", "and caspase 7. the cleavage", "caspase 7. the cleavage products", "7. the cleavage products of", "the cleavage products of hur", "cleavage products of hur in", "products of hur in turn", "of hur in turn promote", "hur in turn promote apoptosis." ] }, { "record_id": "GLY_000594_1_393", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "451927", "r hsa", "hsa 451927", "r hsa 451927" ] }, { "record_id": "GLY_000594_1_393", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 2", "2 family", "family signaling", "interleukin 2 family", "2 family signaling", "interleukin 2 family signaling", "the interleukin", "also called", "called the", "the common", "common gamma", "gamma chain", "chain cytokine", "cytokine family", "consists of", "of interleukin", "il 2", "il15 and", "and il21.", "il21. although", "although sometimes", "sometimes considered", "considered to", "to be", "be within", "within this", "this family", "the il4", "il4 and", "and il7", "il7 receptors", "receptors can", "can form", "form complexes", "complexes with", "with other", "other receptor", "receptor chains", "chains and", "and are", "are represented", "represented separately", "separately in", "in reactome.", "reactome. receptors", "receptors of", "of this", "family associate", "associate with", "with jak1", "jak1 and", "and 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this", "be within this family", "this family the", "family the il4", "the il4 and il7", "il4 and il7 receptors", "and il7 receptors can", "il7 receptors can form", "receptors can form complexes", "can form complexes with", "form complexes with other", "complexes with other receptor", "with other receptor chains", "other receptor chains and", "receptor chains and are", "chains and are represented", "and are represented separately", "are represented separately in", "represented separately in reactome.", "separately in reactome. receptors", "in reactome. receptors of", "reactome. receptors of this", "receptors of this family", "of this family associate", "this family associate with", "family associate with jak1", "associate with jak1 and", "with jak1 and jak3", "and jak3 primarily", "jak3 primarily activating", "activating stat5 although", "stat5 although certain", "although certain family members", "certain family members can", "family members can also", "members can also activate", "can also activate stat1", "activate stat1 stat3", "stat1 stat3 or", "interleukin 2 family also", "2 family also called", "family also called the", "also called the common gamma", "called the common gamma chain", "the common gamma chain cytokine", "common gamma chain cytokine family", "chain cytokine family consists", "cytokine family consists of", "family consists of interleukin", "consists of interleukin il", "of interleukin il 2", "2 il9 il15", "il9 il15 and il21.", "il15 and il21. although sometimes", "and il21. although sometimes considered", "il21. although sometimes considered to", "although sometimes considered to be", "sometimes considered to be within", "considered to be within this", "to be within this family", "within this family the", "this family the il4", "family the il4 and", "the il4 and il7 receptors", "il4 and il7 receptors can", "and il7 receptors can form", "il7 receptors can form complexes", "receptors can form complexes with", "can form complexes with other", "form 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stat1 stat3", "activate stat1 stat3 or", "stat1 stat3 or stat6." ] }, { "record_id": "GLY_000594_1_394", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4551638", "r hsa", "hsa 4551638", "r hsa 4551638" ] }, { "record_id": "GLY_000594_1_394", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sumoylation of", "of chromatin", "chromatin organization", "organization proteins", "sumoylation of chromatin", "of chromatin organization", "chromatin organization proteins", "sumoylation of chromatin organization", "of chromatin organization proteins", "sumoylation of chromatin organization proteins", "of proteins", "proteins involved", "involved in", "in chromatin", "regulates gene", "gene expression", "expression in", "in several", "several ways:", "ways: direct", "direct influence", "influence on", "on catalytic", "catalytic activity", "activity of", "of enzymes", "enzymes that", "that modify", "modify 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"thrombin but to", "but to be", "to be unnecessary", "be unnecessary at", "unnecessary at higher", "at higher agonist", "higher agonist concentrations", "concentrations g12", "g12 appears to", "appears to be", "to be dispensable", "be dispensable for", "dispensable for thrombin", "for thrombin signaling", "thrombin signaling in", "signaling in platelets.", "in platelets. g", "platelets. g alpha", "alpha q", "q activates", "activates phospholipase c", "phospholipase c beta", "c beta thereby", "beta thereby triggering", "thereby triggering phosphoinositide", "triggering phosphoinositide hydrolysis", "hydrolysis calcium", "calcium mobilization and", "mobilization and protein", "and protein kinase", "protein kinase c", "kinase c activation.", "c activation. this", "activation. this provides", "this provides a", "provides a path", "a path to", "path to calcium", "to calcium regulated", "calcium regulated kinases", "regulated kinases and", "kinases and phosphatases", "phosphatases gefs", 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"'sheddases' that liberate", "that liberate ligands", "liberate ligands for", "ligands for receptor", "for receptor tyrosine", "receptor tyrosine kinases", "kinases providing", "providing a link", "a link between", "link between thrombin", "between thrombin and", "thrombin and receptor", "and receptor tyrosine", "tyrosine kinases involved", "kinases involved in", "involved in cell", "in cell growth", "cell growth and", "growth and differentiation.", "and differentiation. the", "differentiation. the pleiotrophic", "the pleiotrophic effects", "pleiotrophic effects of", "effects of par", "of par activation", "par activation are", "activation are consistent", "are consistent with", "consistent with many", "with many of", "many of thrombin's", "of thrombin's diverse", "thrombin's diverse actions", "diverse actions on", "actions on cells.", "thrombin activates proteinase activated", "activates proteinase activated receptors", "pars that signal", "that signal through heterotrimeric", "signal through heterotrimeric g", "through heterotrimeric g proteins", "heterotrimeric g proteins of", "g proteins of the", "proteins of the g12/13", "of the g12/13 and", "the g12/13 and gq", "g12/13 and gq families", "gq families thereby", "families thereby connecting", "thereby connecting to a", "connecting to a host", "to a host of", "a host of intracellular", "host of intracellular signaling", "of intracellular signaling pathways.", "intracellular signaling pathways. thrombin", "signaling pathways. thrombin activates", "pathways. thrombin activates pars", "thrombin activates pars by", "activates pars by cleaving", "pars by cleaving an", "by cleaving an n", "cleaving an n terminal", "an n terminal peptide", "n terminal peptide that", "terminal peptide that then", "peptide that then binds", "that then binds to", "then binds to the", "binds to the body", "to the body of", "the body of the", "body of the receptor", "of the receptor to", "the receptor to effect", "receptor to effect 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thrombin", "the predominant thrombin receptor", "predominant thrombin receptor followed", "thrombin receptor followed by", "receptor followed by par4", "followed by par4 which", "by par4 which is", "par4 which is less", "which is less responsive", "is less responsive to", "less responsive to thrombin.", "responsive to thrombin. par", "to thrombin. par 3", "thrombin. par 3 is", "par 3 is not", "3 is not considered", "is not considered important", "not considered important for", "considered important for human", "important for human platelet", "for human platelet responses", "human platelet responses as", "platelet responses as it", "responses as it is", "as it is minimally", "it is minimally expressed", "minimally expressed though", "expressed though this", "though this is not", "this is not the", "is not the case", "not the case for", "the case for mouse.", "case for mouse. par2", "for mouse. par2 is", "mouse. par2 is not", "par2 is not expressed", "is not expressed in", "not expressed in platelets.", "expressed in platelets. in", "in platelets. in mouse", "platelets. in mouse platelets", "mouse platelets gq", "platelets gq is", "gq is necessary for", "is necessary for platelet", "necessary for platelet secretion", "for platelet secretion and", "platelet secretion and aggregation", "secretion and aggregation in", "and aggregation in response", "aggregation in response to", "in response to thrombin", "response to thrombin but", "to thrombin but is", "thrombin but is not", "but is not necessary", "is not necessary for", "not necessary for thrombin", "necessary for thrombin triggered", "for thrombin triggered shape", "thrombin triggered shape change.", "triggered shape change. g13", "shape change. g13 appears", "change. g13 appears to", "g13 appears to contribute", "appears to contribute to", "to contribute to platelet", "contribute to platelet aggregation", "to platelet aggregation as", "platelet aggregation as well", "aggregation as well as", "as well as shape", "well as shape change", "as shape change in", "shape change in response", "change in response to", "in response to low", "response to low concentrations", "to low concentrations of", "low concentrations of thrombin", "concentrations of thrombin but", "of thrombin but to", "thrombin but to be", "but to be unnecessary", "to be unnecessary at", "be unnecessary at higher", "unnecessary at higher agonist", "at higher agonist concentrations", "agonist concentrations g12", "concentrations g12 appears", "g12 appears to be", "appears to be dispensable", "to be dispensable for", "be dispensable for thrombin", "dispensable for thrombin signaling", "for thrombin signaling in", "thrombin signaling in platelets.", "signaling in platelets. g", "in platelets. g alpha", "g alpha q", "q activates phospholipase", "activates phospholipase c beta", "phospholipase c beta thereby", "c beta thereby triggering", "beta thereby triggering phosphoinositide", "thereby triggering phosphoinositide hydrolysis", "phosphoinositide hydrolysis calcium", "hydrolysis calcium mobilization", "calcium mobilization and protein", "mobilization and protein kinase", "and protein kinase c", "protein kinase c activation.", "kinase c activation. this", "c activation. this provides", "activation. this provides a", "this provides a path", "provides a path to", "a path to calcium", "path to calcium regulated", "to calcium regulated kinases", "calcium regulated kinases and", "regulated kinases and phosphatases", "and phosphatases gefs", "gefs map kinase", "map kinase cassettes and", "kinase cassettes and other", "cassettes and other proteins", "and other proteins that", "other proteins that mediate", "proteins that mediate cellular", "that mediate cellular responses", "mediate cellular responses ranging", "cellular responses ranging from", "responses ranging from granule", "ranging from granule secretion", "granule secretion integrin", "secretion integrin activation", "integrin activation and", "activation and aggregation", "and aggregation in platelets.", "aggregation in platelets. gbeta:gamma", "in platelets. gbeta:gamma subunits", "platelets. gbeta:gamma subunits can", "gbeta:gamma subunits can activate", "subunits can activate phosphoinositide", "can activate phosphoinositide 3", "activate phosphoinositide 3 kinase", "phosphoinositide 3 kinase and", "3 kinase and other", "kinase and other lipid", "and other lipid modifying", "other lipid modifying enzymes", "modifying enzymes protein", "enzymes protein kinases", "protein kinases and", "kinases and channels.", "and channels. par1 activation", "channels. par1 activation indirectly", "par1 activation indirectly leads", "activation indirectly leads to", "indirectly leads to activation", "leads to activation of", "to activation of cell", "activation of cell surface", "of cell surface 'sheddases'", "cell surface 'sheddases' that", "surface 'sheddases' that liberate", "'sheddases' that liberate ligands", "that liberate ligands for", "liberate ligands for receptor", "ligands for receptor tyrosine", "for receptor tyrosine kinases", "tyrosine kinases providing", "kinases providing a", "providing a link between", "a link between thrombin", "link between thrombin and", "between thrombin and receptor", "thrombin and receptor tyrosine", "and receptor tyrosine kinases", "receptor tyrosine kinases involved", "tyrosine kinases involved in", "kinases involved in cell", "involved in cell growth", "in cell growth and", "cell growth and differentiation.", "growth and differentiation. the", "and differentiation. the pleiotrophic", "differentiation. the pleiotrophic effects", "the pleiotrophic effects of", "pleiotrophic effects of par", "effects of par activation", "of par activation are", "par activation are consistent", "activation are consistent with", "are consistent with many", "consistent with many of", "with many of thrombin's", "many of thrombin's diverse", "of thrombin's diverse actions", "thrombin's diverse actions on", "diverse actions on cells.", "thrombin activates proteinase activated receptors", "receptors pars that", "pars that signal through", "that signal through heterotrimeric g", "signal through heterotrimeric g proteins", "through heterotrimeric g proteins of", "heterotrimeric g proteins of the", "g proteins of the g12/13", "proteins of the g12/13 and", "of the g12/13 and gq", "the g12/13 and gq families", "and gq families thereby", "gq families thereby connecting", "families thereby connecting to", "thereby connecting to a host", "connecting to a host of", "to a host of intracellular", "a host of intracellular signaling", "host of intracellular signaling pathways.", "of intracellular signaling pathways. thrombin", "intracellular signaling pathways. thrombin activates", "signaling pathways. thrombin activates pars", "pathways. thrombin activates pars by", "thrombin activates pars by cleaving", "activates pars by cleaving an", "pars by cleaving an n", "by cleaving an n terminal", "cleaving an n terminal peptide", "an n terminal peptide that", "n terminal peptide that then", "terminal peptide that then binds", "peptide that then binds to", "that then binds to the", "then binds to the body", "binds to the body of", "to the body of the", "the body of the receptor", "body of the receptor to", "of the receptor to effect", "the receptor to effect transmembrane", "receptor to effect transmembrane signaling.", "to effect transmembrane signaling. intermolecular", "effect transmembrane signaling. intermolecular ligation", "transmembrane signaling. intermolecular ligation of", "signaling. intermolecular ligation of one", "intermolecular ligation of one par", "ligation of one par molecule", "of one par molecule by", "one par molecule by another", "par molecule by another can", "molecule by another can occur", "by another can occur but", "another can occur but is", "can occur but is less", "occur but is less efficient", "but is less efficient than", "is less efficient than self", "less 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receptor cleavage. pars are", "receptor cleavage. pars are key", "cleavage. pars are key to", "pars are key to platelet", "are key to platelet activation.", "key to platelet activation. four", "to platelet activation. four pars", "platelet activation. four pars have", "activation. four pars have been", "four pars have been identified", "have been identified of", "been identified of which", "identified of which pars", "which pars 1 3", "pars 1 3 and", "1 3 and 4", "3 and 4 are substrates", "and 4 are substrates for", "4 are substrates for thrombin.", "are substrates for thrombin. in", "substrates for thrombin. in humans", "for thrombin. in humans par", "thrombin. in humans par 1", "in humans par 1 is", "humans par 1 is the", "par 1 is the predominant", "1 is the predominant thrombin", "is the predominant thrombin receptor", "the predominant thrombin receptor followed", "predominant thrombin receptor followed by", "thrombin receptor followed by par4", "receptor followed by par4 which", "followed by par4 which is", "by par4 which is less", "par4 which is less responsive", "which is less responsive to", "is less responsive to thrombin.", "less responsive to thrombin. par", "responsive to thrombin. par 3", "to thrombin. par 3 is", "thrombin. par 3 is not", "par 3 is not considered", "3 is not considered important", "is not considered important for", "not considered important for human", "considered important for human platelet", "important for human platelet responses", "for human platelet responses as", "human platelet responses as it", "platelet responses as it is", "responses as it is minimally", "as it is minimally expressed", "is minimally expressed though", "minimally expressed though this", "expressed though this is", "though this is not the", "this is not the case", "is not the case for", "not the case for mouse.", "the case for mouse. par2", "case for mouse. par2 is", "for mouse. par2 is not", "mouse. par2 is not expressed", "par2 is not expressed in", "is not expressed in platelets.", "not expressed in platelets. in", "expressed in platelets. in mouse", "in platelets. in mouse platelets", "in mouse platelets gq", "mouse platelets gq is", "platelets gq is necessary", "gq is necessary for platelet", "is necessary for platelet secretion", "necessary for platelet secretion and", "for platelet secretion and aggregation", "platelet secretion and aggregation in", "secretion and aggregation in response", "and aggregation in response to", "aggregation in response to thrombin", "in response to thrombin but", "response to thrombin but is", "to thrombin but is not", "thrombin but is not necessary", "but is not necessary for", "is not necessary for thrombin", "not necessary for thrombin triggered", "necessary for thrombin triggered shape", "for thrombin triggered shape change.", "thrombin triggered shape change. g13", "triggered shape change. g13 appears", "shape change. g13 appears to", "change. g13 appears to contribute", "g13 appears to contribute to", "appears to contribute to platelet", "to contribute to platelet aggregation", "contribute to platelet aggregation as", "to platelet aggregation as well", "platelet aggregation as well as", "aggregation as well as shape", "as well as shape change", "well as shape change in", "as shape change in response", "shape change in response to", "change in response to low", "in response to low concentrations", "response to low concentrations of", "to low concentrations of thrombin", "low concentrations of thrombin but", "concentrations of thrombin but to", "of thrombin but to be", "thrombin but to be unnecessary", "but to be unnecessary at", "to be unnecessary at higher", "be unnecessary at higher agonist", "unnecessary at higher agonist concentrations", "higher agonist concentrations g12", "agonist concentrations g12 appears", "concentrations g12 appears to", "g12 appears to be dispensable", "appears to be dispensable for", "to be dispensable for thrombin", "be dispensable for thrombin signaling", "dispensable for thrombin signaling in", "for thrombin signaling in platelets.", "thrombin signaling in platelets. g", "signaling in platelets. g alpha", "platelets. g alpha q", "alpha q activates", "q activates phospholipase c", "activates phospholipase c beta thereby", "phospholipase c beta thereby triggering", "c beta thereby triggering phosphoinositide", "beta thereby triggering phosphoinositide hydrolysis", "triggering phosphoinositide hydrolysis calcium", "phosphoinositide hydrolysis calcium mobilization", "hydrolysis calcium mobilization and", "calcium mobilization and protein kinase", "mobilization and protein kinase c", "and protein kinase c activation.", "protein kinase c activation. this", "kinase c activation. this provides", "c activation. this provides a", "activation. this provides a path", "this provides a path to", "provides a path to calcium", "a path to calcium regulated", "path to calcium regulated kinases", "to calcium regulated kinases and", "calcium regulated kinases and phosphatases", "kinases and phosphatases gefs", "phosphatases gefs map", "gefs map kinase cassettes", "map kinase cassettes and other", "kinase cassettes and other proteins", "cassettes and other proteins that", "and other proteins that mediate", "other proteins that mediate cellular", "proteins that mediate cellular responses", "that mediate cellular responses ranging", "mediate cellular responses ranging from", "cellular responses ranging from granule", "responses ranging from granule secretion", "from granule secretion integrin", "granule secretion integrin activation", "integrin activation and aggregation", "activation and aggregation in", "and aggregation in platelets. gbeta:gamma", "aggregation in platelets. gbeta:gamma subunits", "in platelets. gbeta:gamma subunits can", "platelets. gbeta:gamma subunits can activate", "gbeta:gamma subunits can activate phosphoinositide", "subunits can activate phosphoinositide 3", "can activate phosphoinositide 3 kinase", 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", "upon stimulation with wnt", "stimulation with wnt ligand", "wnt ligand axin", "ligand axin and", "axin and gsk3beta are", "and gsk3beta are recruited", "gsk3beta are recruited to", "are recruited to the", "recruited to the plasma", "to the plasma membrane", "the plasma membrane through", "plasma membrane through interaction", "membrane through interaction with", "through interaction with dvl", "with dvl tamai", "dvl tamai et", "et al 2004", "2004 mao et", "et al 2001", "2001 reviewed in", "reviewed in he et", "in he et al", "al 2004 .", "2004 . polymerization", ". polymerization of", "polymerization of membrane associated", "of membrane associated dvl", "membrane associated dvl and", "associated dvl and gsk3beta", "and gsk3beta and", "gsk3beta and csnk1", "and csnk1 mediated phosphorylation", "csnk1 mediated phosphorylation of", "mediated phosphorylation of lrp5/6", "phosphorylation of lrp5/6 establish", "of lrp5/6 establish a", "lrp5/6 establish a feed", "establish a feed forward", "a feed forward mechanism", "feed forward mechanism for", "forward mechanism for enhanced", "mechanism for enhanced membrane", "for enhanced membrane recruitment", "enhanced membrane recruitment of", "membrane recruitment of axin", "recruitment of axin upon", "of axin upon wnt", "axin upon wnt signaling", "wnt signaling tamai", "signaling tamai et", "2004 cong et", "2004 zeng et", "et al 2005", "2005 bilic et", "et al 2007", "al 2007 .", ". in", "xenopus oocytes but", "oocytes but not", "but not necessarily all", "not necessarily all sytems", "all sytems axin", "sytems axin is", "axin is present in", "is present in limiting", "present in limiting concentrations", "in limiting concentrations and", "limiting concentrations and is", "concentrations and is considered", "and is considered rate", "is considered rate limiting", "considered rate limiting for", "rate limiting for the", "limiting for the assembly", "for the assembly of", "the assembly of the", "assembly of the destruction", "destruction complex lee", "complex lee et", "et al 2003", "2003 benchabane et", "et al 2008", "2008 tan", "et al 2012", "2012 reviewed in", "reviewed in macdonald et", "in macdonald et al", "et al 2009", "al 2009 .", "2009 . the", ". the recruitment", "the recruitment of axin", "recruitment of axin away", "of axin away from", "axin away from the", "away from the destruction", "from the destruction complex", "the destruction complex upon", "destruction complex upon wnt", "complex upon wnt stimulation", "upon wnt stimulation effectively", "wnt stimulation effectively destabilizes", "stimulation effectively destabilizes the", "effectively destabilizes the destruction", "destabilizes the destruction complex", "destruction complex and contributes", "complex and contributes to", "and contributes to the", "contributes to the accumulation", "to the accumulation of", "the accumulation of free", "accumulation of free beta", "of free beta catenin", "beta catenin kikuchi", "1999 lee et", "al 2003 .", "2003 . axin", ". axin association", "axin association with the", "association with the destruction", "with the destruction complex", "the destruction complex is", "destruction complex is also", "complex is also regulated", "is also regulated by", "also regulated by phosphorylation.", "by phosphorylation. in", "phosphorylation. in the", "in the active destruction", "the active destruction complex", "destruction complex axin", "complex axin is", "axin is phosphorylated by", "is phosphorylated by gsk3beta", "by gsk3beta dephosphorylation", "gsk3beta dephosphorylation by", "dephosphorylation by protein phosphatase", "by protein phosphatase 1", "phosphatase 1 pp1", "pp1 or protein", "or protein phosphatase 2a", "phosphatase 2a pp2a", "pp2a destabilizes the", "destabilizes the interaction of", "the interaction of axin", "interaction of axin with", "of axin with the", "axin with the other", "with the other components", "the other components of", "other components of the", "components of the destruction", "destruction complex and promotes", "complex and promotes its", "and promotes its disassembly", "its disassembly luo", "disassembly luo et", "2007 willert et", "et al 1999", "1999 jho et", "al 1999 .", "1999 . free", ". free axin", "free axin is also", "axin is also subject", "is also subject to", "also subject to degradation", "subject to degradation by", "to degradation by the", "degradation by the 26s", "by the 26s proteasome", "the 26s proteasome in", "26s proteasome in a", "proteasome in a manner", "in a manner that", "a manner that depends", "manner that depends on", "that depends on the", "depends on the poly", "on the poly adp", "the poly adp ribosylating", "poly adp ribosylating enzymes", "adp ribosylating enzymes tankyrase", "ribosylating enzymes tankyrase 1", "enzymes tankyrase 1 and", "tankyrase 1 and 2", "and 2 huang", "2 huang et", "2009 .
", "upon stimulation with wnt ligand", "with wnt ligand axin", "wnt ligand axin and", "ligand axin and gsk3beta", "axin and gsk3beta are recruited", "and gsk3beta are recruited to", "gsk3beta are recruited to the", "are recruited to the plasma", "recruited to the plasma membrane", "to the plasma membrane through", "the plasma membrane through interaction", "plasma membrane through interaction with", "membrane through interaction with dvl", "interaction with dvl tamai", "with dvl tamai et", "dvl tamai et al", "tamai et al 2004", "al 2004 mao", "2004 mao et al", "mao et al 2001", "al 2001 reviewed", "2001 reviewed in he", "reviewed in he et al", "he et al 2004", "et al 2004 .", "2004 . polymerization of", ". polymerization of membrane", "polymerization of membrane associated dvl", "of membrane associated dvl and", "membrane associated dvl and gsk3beta", "dvl and gsk3beta and", "and gsk3beta and csnk1", "gsk3beta and csnk1 mediated", "and csnk1 mediated phosphorylation of", "csnk1 mediated phosphorylation of lrp5/6", "mediated phosphorylation of lrp5/6 establish", "phosphorylation of lrp5/6 establish a", "of lrp5/6 establish a feed", "lrp5/6 establish a feed forward", "establish a feed forward mechanism", "a feed forward mechanism for", "feed forward mechanism for enhanced", "forward mechanism for enhanced membrane", "mechanism for enhanced membrane recruitment", "for enhanced membrane recruitment of", "enhanced membrane recruitment of axin", "membrane recruitment of axin upon", "recruitment of axin upon wnt", "of axin upon wnt signaling", "upon wnt signaling tamai", "wnt signaling tamai et", "signaling tamai et al", "al 2004 cong", "2004 cong et al", "cong et al 2004", "al 2004 zeng", "2004 zeng et al", "zeng et al 2005", "al 2005 bilic", "2005 bilic et al", "bilic et al 2007", "et al 2007 .", "2007 . in", ". in xenopus", "in xenopus oocytes but", "xenopus oocytes but not", "oocytes but not necessarily", "but not necessarily all sytems", "necessarily all sytems axin", "all sytems axin is", "sytems axin is present", "axin is present in limiting", "is present in limiting concentrations", "present in limiting concentrations and", "in limiting concentrations and is", "limiting concentrations and is considered", "concentrations and is considered rate", "and is considered rate limiting", "is considered rate limiting for", "considered rate limiting for the", "rate limiting for the assembly", "limiting for the assembly of", "for the assembly of the", "the assembly of the destruction", "assembly of the destruction complex", "the destruction complex lee", "destruction complex lee et", "complex lee et al", "lee et al 2003", "al 2003 benchabane", "2003 benchabane et al", "benchabane et al 2008", "2008 tan et", "tan et al 2012", "al 2012 reviewed", "2012 reviewed in macdonald", "reviewed in macdonald et al", "macdonald et al 2009", "et al 2009 .", "2009 . the recruitment", ". the recruitment of", "the recruitment of axin away", "recruitment of axin away from", "of axin away from the", "axin away from the destruction", "away from the destruction complex", "from the destruction complex upon", "the destruction complex upon wnt", "destruction complex upon wnt stimulation", "complex upon wnt stimulation effectively", "upon wnt stimulation effectively destabilizes", "wnt stimulation effectively destabilizes the", "stimulation effectively destabilizes the destruction", "effectively destabilizes the destruction complex", "destabilizes the destruction complex and", "the destruction complex and contributes", "destruction complex and contributes to", "complex and contributes to the", "and contributes to the accumulation", "contributes to the accumulation of", "to the accumulation of free", "the accumulation of free beta", "accumulation of free beta catenin", "free beta catenin kikuchi", "catenin kikuchi 1999", "kikuchi 1999 lee", "1999 lee et al", "et al 2003 .", "2003 . axin association", ". axin association with", "axin association with the destruction", "association with the destruction complex", "with the destruction complex is", "the destruction complex is also", "destruction complex is also regulated", "complex is also regulated by", "is also regulated by phosphorylation.", "regulated by phosphorylation. in", "by phosphorylation. in the", "phosphorylation. in the active", "in the active destruction complex", "active destruction complex axin", "destruction complex axin is", "complex axin is phosphorylated", "axin is phosphorylated by gsk3beta", "phosphorylated by gsk3beta dephosphorylation", "by gsk3beta dephosphorylation by", "gsk3beta dephosphorylation by protein", "dephosphorylation by protein phosphatase 1", "protein phosphatase 1 pp1", "1 pp1 or", "pp1 or protein phosphatase", "protein phosphatase 2a pp2a", "2a pp2a destabilizes", "pp2a destabilizes the interaction", "destabilizes the interaction of axin", "the interaction of axin with", "interaction of axin with the", "of axin with the other", "axin with the other components", "with the other components of", "the other components of the", "other components of the destruction", "components of the destruction complex", "the destruction complex and promotes", "destruction complex and promotes its", "complex and promotes its disassembly", "promotes its disassembly luo", "its disassembly luo et", "disassembly luo et al", "luo et al 2007", "al 2007 willert", "2007 willert et al", "willert et al 1999", "al 1999 jho", "1999 jho et al", "jho et al 1999", "et al 1999 .", "1999 . free axin", ". free axin is", "free axin is also subject", "axin is also subject to", "is also subject to degradation", "also subject to degradation by", "subject to degradation by the", "to degradation by the 26s", "degradation by the 26s proteasome", "by the 26s proteasome in", "the 26s proteasome in a", "26s proteasome in a manner", "proteasome in a manner that", "in a manner that depends", "a manner that depends on", "manner that depends on the", "that depends on the poly", "depends on the poly adp", "on the poly adp ribosylating", "the poly adp ribosylating enzymes", "poly adp ribosylating enzymes tankyrase", "adp ribosylating enzymes tankyrase 1", "ribosylating enzymes tankyrase 1 and", "enzymes tankyrase 1 and 2", "1 and 2 huang", "and 2 huang et", "2 huang et al", "huang et al 2009" ] }, { "record_id": "GLY_000594_1_402", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4655427", "r hsa", "hsa 4655427", "r hsa 4655427" ] }, { "record_id": "GLY_000594_1_402", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sumoylation of", "of dna", "dna methylation", "methylation proteins", "sumoylation of dna", "of dna methylation", "dna methylation proteins", "sumoylation of dna methylation", "of dna methylation proteins", "sumoylation of dna methylation proteins", "the known", "known dna", "dna methyltransferases", "and dnmt3b", "can be", "be sumoylated", "reviewed in", "in xu", "xu et", "et al.", "al. 2010", "denis et", "al. 2011", "2011 .", ". sumoylation", "sumoylation affects", "affects the", "the catalytic", "catalytic activity", "activity of", "of dnmt1", "dnmt1 and", "and the", "the protein", "protein interactions", "interactions of", "of dnmt3a.", "the known dna", "known dna methyltransferases", "methyltransferases dnmt1", "dnmt1 dnmt3a", "dnmt3a and", "dnmt3b can", "can be sumoylated", "sumoylated reviewed", "reviewed in xu", "in xu et", "xu et al.", "et al. 2010", "2010 denis", "denis et al.", "et al. 2011", "al. 2011 .", "2011 . sumoylation", ". sumoylation affects", "sumoylation affects the", "affects the catalytic", "the catalytic activity", "catalytic activity of", "activity of dnmt1", "of dnmt1 and", "dnmt1 and the", "and the protein", "the protein interactions", "protein interactions of", "interactions of dnmt3a.", "the known dna methyltransferases", "dna methyltransferases dnmt1", "dnmt3a and dnmt3b", "and dnmt3b can", "dnmt3b can be", "be sumoylated reviewed", "sumoylated reviewed in", "reviewed in xu et", "in xu et al.", "xu et al. 2010", "al. 2010 denis", "2010 denis et", "denis et al. 2011", "et al. 2011 .", "al. 2011 . sumoylation", "2011 . sumoylation affects", ". sumoylation affects the", "sumoylation affects the catalytic", "affects the catalytic activity", "the catalytic activity of", "catalytic activity of dnmt1", "activity of dnmt1 and", "of dnmt1 and the", "dnmt1 and the protein", "and the protein interactions", "the protein interactions of", "protein interactions of dnmt3a.", "known dna methyltransferases dnmt1", "methyltransferases dnmt1 dnmt3a", "dnmt1 dnmt3a and", "and dnmt3b can be", "dnmt3b can be sumoylated", "can be sumoylated reviewed", "be sumoylated reviewed in", "sumoylated reviewed in xu", "reviewed in xu et al.", "in xu et al. 2010", "et al. 2010 denis", "al. 2010 denis et", "2010 denis et al.", "denis et al. 2011 .", "et al. 2011 . sumoylation", "al. 2011 . sumoylation affects", "2011 . sumoylation affects the", ". sumoylation affects the catalytic", "sumoylation affects the catalytic activity", "affects the catalytic activity of", "the catalytic activity of dnmt1", "catalytic activity of dnmt1 and", "activity of dnmt1 and the", "of dnmt1 and the protein", "dnmt1 and the protein interactions", "and the protein interactions of", "the protein interactions of dnmt3a." ] }, { "record_id": "GLY_000594_1_403", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "499943", "r hsa", "hsa 499943", "r hsa 499943" ] }, { "record_id": "GLY_000594_1_403", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interconversion of", "of nucleotide", "nucleotide di", "and triphosphates", "interconversion of nucleotide", "of nucleotide di", "di and", "interconversion of nucleotide di", "nucleotide di and", "di and triphosphates", "of nucleotide di and", "nucleotide di and triphosphates", "an array", "array of", "of kinases", "kinases catalyze", "catalyze the", "the reversible", "reversible phosphorylation", "phosphorylation of", "nucleotide monophosphates", "monophosphates to", "to form", "form nucleotide", "nucleotide diphosphates", "diphosphates and", "and triphosphates.

nucleoside", "triphosphates.

nucleoside monophosphate", "monophosphate kinases", "of nucleoside", "nucleoside and", "and deoxynucleoside", "deoxynucleoside 5'", "5' monophosphates", "form the", "the corresponding", "corresponding nucleoside", "nucleoside 5'", "5' diphosphates.", "most appear", "appear to", "to have", "have restricted", "restricted specificities", "specificities for", "for nucleoside", "nucleoside monophosphates", "and to", "to use", "use atp", "atp preferentially", "van rompay", "rompay et", "et al.", "al. 2000", "anderson 1973", "noda 1973", "1973 .", "the total", "total number", "number of", "of human", "human enzymes", "enzymes that", "that catalyze", "catalyze these", "these reactions", "reactions in", "in vivo", "vivo is", "is not", "not clear.", "in six", "six cases", "a well", "well defined", "defined biochemical", "biochemical activity", "activity has", "has been", "been associated", "associated with", "with a", "a purified", "purified protein", "and these", "these are", "are annotated", "annotated here.", "additional nucleoside", "nucleoside monophosphate", "monophosphate kinase", "kinase like", "like human", "human proteins", "proteins have", "have been", "been identified", "identified in", "in molecular", "molecular cloning", "cloning studies", "studies whose", "whose enzymatic", "enzymatic activities", "activities are", "are unknown", "and several", "several distinctive", "distinctive nucleoside", "kinase activities", "activities detected", "detected in", "in cell", "cell extracts", "a gtp", "gtp requiring", "requiring adenylate", "adenylate kinase", "kinase activity", "wilson et", "al. 1976", "and one", "one or", "or more", "more guanylate", "guanylate kinase", "jamil et", "al. 1975", "have not", "not been", "been unambiguously", "unambiguously associated", "with specific", "specific human", "human proteins.

the", "proteins.

the nucleoside", "monophosphates against", "against which", "which each", "each of", "of the", "the six", "six well", "well characterized", "characterized enzymes", "enzymes is", "is active", "active is", "is shown", "shown in", "in the", "the table", "2000 .", "all six", "six efficiently", "efficiently use", "atp as", "as a", "a phosphate", "phosphate donor", "but have", "have some", "some activity", "activity with", "with other", "other nucleoside", "nucleoside triphosphates", "triphosphates as", "as well", "well in", "in vitro.", "the high", "high concentrations", "concentrations of", "of atp", "atp relative", "relative to", "to other", "triphosphates in", "vivo makes", "makes it", "it the", "the likely", "likely major", "major phosphate", "donor in", "in these", "reactions under", "under most", "most conditions.

all", "conditions.

all of", "of these", "these phosphorylation", "phosphorylation reactions", "reactions are", "are freely", "freely reversible", "reversible in", "in vitro", "vitro when", "when carried", "carried out", "out with", "with purified", "purified enzymes", "enzymes and", "and substrates", "having equilibrium", "equilibrium constants", "constants near", "near 1.", "high ratios", "ratios of", "atp to", "to adp", "adp are", "are likely", "likely to", "to favor", "favor the", "the forward", "forward direction", "direction of", "the conversion", "conversion of", "d nmp", "nmp and", "and atp", "d ndp", "ndp and", "and adp.", "at the", "the same", "same time", "the reversibility", "reversibility of", "the reactions", "reactions and", "and the", "the overlapping", "overlapping substrate", "substrate specificities", "specificities of", "the enzymes", "enzymes raises", "raises the", "the possibility", "possibility that", "that this", "this group", "group of", "of reactions", "reactions can", "can buffer", "buffer the", "the intracellular", "intracellular nucleotide", "nucleotide pool", "pool and", "and regulate", "regulate the", "the relative", "relative concentrations", "of individual", "individual nucleotides", "nucleotides in", "the pool:", "pool: if", "if any", "any one", "one molecule", "molecule builds", "builds up", "up to", "to unusually", "unusually high", "high levels", "multiple routes", "routes appear", "to be", "be open", "open not", "not only", "only to", "to dispose", "dispose of", "of it", "it but", "but to", "use it", "it to", "to increase", "increase the", "the supply", "supply of", "of less", "less abundant", "abundant nucleotides.

ribonucleotide", "nucleotides.

ribonucleotide reductase", "reductase catalyzes", "catalyzes the", "the synthesis", "synthesis of", "of deoxyribonucleotide", "deoxyribonucleotide diphosphates", "diphosphates from", "from ribonucleotide", "ribonucleotide diphosphates.", "an array of", "array of kinases", "of kinases catalyze", "kinases catalyze the", "catalyze the reversible", "the reversible phosphorylation", "reversible phosphorylation of", "phosphorylation of nucleotide", "of nucleotide monophosphates", "nucleotide monophosphates to", "monophosphates to form", "to form nucleotide", "form nucleotide diphosphates", "nucleotide diphosphates and", "diphosphates and triphosphates.

nucleoside", "and triphosphates.

nucleoside monophosphate", "triphosphates.

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nucleoside", "nucleotide diphosphates and triphosphates.

nucleoside monophosphate", "diphosphates and triphosphates.

nucleoside monophosphate kinases", "and triphosphates.

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", "domains.

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", ".

all", "all three", "three receptors", "receptors have", "have alpha", "chains that", "that bind", "bind their", "their specific", "specific ligands", "ligands with", "with low", "low affinity", "de groot", "groot et", "al. 1998", "1998 .", ". bc", "bc then", "then associates", "associates with", "with the", "the alpha", "alpha chain", "chain forming", "forming a", "a high", "high affinity", "affinity receptor", "geijsen et", "al. 2001", "though the", "the in", "in vivo", "vivo receptor", "receptor is", "is likely", "likely be", "be a", "a higher", "higher order", "order multimer", "multimer as", "as recently", "recently demonstrated", "demonstrated for", "the gm", "csf receptor", "hansen et", "al. 2008", "2008 .

", ".

the", "the receptor", "receptor chains", "chains lack", "lack intrinsic", "intrinsic kinase", "kinase activity", "instead they", "they interact", "interact with", "with and", "and activate", "activate signaling", "signaling kinases", "notably janus", "janus kinase", "kinase 2", "jak2 .", ". these", "these phosphorylate", "phosphorylate the", "allowing recruitment", "recruitment of", "of signaling", "signaling molecules", "molecules such", "as shc", "the phosphatidylinositol", "phosphatidylinositol 3", "3 kinases", "the signal", "signal transducers", "transducers and", "and activators", "activators of", "of transcription", "stats .", ". the", "cytoplasmic domain", "domain of", "of bc", "bc has", "has two", "two distinct", "distinct functional", "functional domains:", "domains: the", "the membrane", "membrane proximal", "proximal region", "region mediates", "mediates the", "the induction", "induction of", "of proliferation", "proliferation associated", "associated genes", "genes such", "as c", "c myc", "pim 1", "1 and", "and oncostatin", "oncostatin m.", "m. this", "this region", "region binds", "binds multiple", "multiple signal", "signal transducing", "transducing proteins", "proteins including", "including jak2", "quelle et", "al. 1994", "c src", "src and", "and pi3", "pi3 kinase", "rao and", "and mufson", "1995 .", "membrane distal", "distal domain", "domain is", "for cytokine", "cytokine induced", "induced growth", "growth inhibition", "inhibition and", "and is", "is necessary", "necessary for", "the viability", "viability of", "of hematopoietic", "hematopoietic cells", "inhorn et", "al. 1995", ". this", "region interacts", "interacts with", "with signal", "proteins such", "and shp", "shp and", "and mediates", "the transcriptional", "transcriptional activation", "activation of", "of c", "c fos", "c jun", "c raf", "raf and", "and p70s6k", "reddy et", "al. 2000", "2000 .



figure", ".



figure reproduced", "reproduced by", "by permission", "permission from", "from macmillan", "macmillan publishers", "publishers ltd:", "ltd: leukemia", "wl blalock", "blalock et", "al. 13:1109", "13:1109 1166", "copyright 1999.", "1999. note", "note that", "that residue", "residue numbering", "numbering in", "in this", "this diagram", "diagram refers", "refers to", "to the", "the mature", "mature common", "beta chain", "chain with", "signal peptide", "peptide removed.", "the interleukin 3", "3 il", "il 5 and", "5 and granulocyte", "and granulocyte macrophage", "granulocyte macrophage colony", "macrophage colony stimulating", "colony stimulating factor", "factor gm", "csf receptors", "receptors form a", "form a family", "a family of", "family of heterodimeric", "of heterodimeric receptors", "heterodimeric receptors that", "receptors that have", "that have specific", "have specific alpha", "specific alpha chains", "alpha chains but", "chains but share", "but share a", "share a common", "a common beta", "common beta subunit", "subunit often", "often referred to", "referred to as", "to as the", "as the common", "the common beta", "beta bc", "bc . both", ". both subunits", "both subunits contain", "subunits contain extracellular", "contain extracellular conserved", "extracellular conserved motifs", "conserved motifs typical", "motifs typical of", "typical of the", "of the cytokine", "the cytokine receptor", "cytokine receptor superfamily.", "receptor superfamily. the", "superfamily. the cytoplasmic", "the cytoplasmic domains", "cytoplasmic domains have", "domains have limited", "have limited similarity", "limited similarity with", "similarity with other", "with other cytokine", "other cytokine receptors", "cytokine receptors and", "receptors and lack", "and lack detectable", "lack detectable catalytic", "detectable catalytic domains", "catalytic domains such", "domains such as", "such as tyrosine", "as tyrosine kinase", "tyrosine kinase domains.

", "kinase domains.

il", "domains.

il 3", "il 3 is", "3 is a", "is a 20", "a 20 26", "20 26 kda", "26 kda product", "kda product of", "product of cd4+", "of cd4+ t", "cd4+ t cells", "t cells that", "cells that acts", "that acts on", "acts on the", "on the most", "the most immature", "most immature marrow", "immature marrow progenitors.", "marrow progenitors. il", "progenitors. il 3", "3 is capable", "is capable of", "capable of inducing", "of inducing the", "inducing the growth", "the growth and", "growth and differentiation", "and differentiation of", "differentiation of multi", "of multi potential", "multi potential hematopoietic", "potential hematopoietic stem", "hematopoietic stem cells", "cells neutrophils", "neutrophils eosinophils", "eosinophils megakaryocytes", "megakaryocytes macrophages", "macrophages lymphoid", "lymphoid and erythroid", "and erythroid cells.", "erythroid cells. il", "cells. il 3", "il 3 has", "3 has been", "has been used", "been used to", "used to support", "to support the", "support the proliferation", "the proliferation of", "proliferation of murine", "of murine cell", "murine cell lines", "cell lines with", "lines with properties", "with properties of", "properties of multi", "multi potential progenitors", "progenitors immature", "immature myeloid as", "myeloid as well", "as well as", "well as t", "as t and", "t and pre", "and pre b", "pre b lymphoid", "b lymphoid cells", "cells miyajima", "miyajima et al.", "et al. 1992", "al. 1992 .", "1992 . il", ". il 5", "il 5 is", "5 is a", "is a hematopoietic", "a hematopoietic growth", "hematopoietic growth factor", "growth factor responsible", "factor responsible for", "responsible for the", "for the maturation", "the maturation and", "maturation and differentiation", "differentiation of eosinophils.", "of eosinophils. it", "eosinophils. it was", "it was originally", "was originally defined", "originally defined as", "defined as a", "as a t", "a t cell", "t cell derived", "cell derived cytokine", "derived cytokine that", "cytokine that triggers", "that triggers activated", "triggers activated b", "activated b cells", "b cells for", "cells for terminal", "for terminal differentiation", "terminal differentiation into", "differentiation into antibody", "into antibody secreting", "antibody secreting plasma", "secreting plasma cells.", "plasma cells. it", "cells. it also", "it also promotes", "also promotes the", "promotes the generation", "the generation of", "generation of cytotoxic", "of cytotoxic t", "cytotoxic t cells", "t cells from", "cells from thymocytes.", "from thymocytes. il", "thymocytes. il 5", "il 5 induces", "5 induces the", "induces the expression", "the expression of", "expression of il", "of il 2", "il 2 receptors", "receptors kouro", "kouro & takatsu", "& takatsu 2009", "takatsu 2009 .", "2009 . gm", ". gm csf", "gm csf is", "csf is produced", "is produced by", "produced by cells", "cells t", "lymphocytes tissue", "macrophages endothelial", "cells mast", "cells found", "found at sites", "at sites of", "sites of inflammatory", "of inflammatory responses.", "inflammatory responses. it", "responses. it stimulates", "it stimulates the", "stimulates the growth", "growth and development", "and development of", "development of progenitors", "of progenitors of", "progenitors of granulocytes", "of granulocytes and", "granulocytes and macrophages", "macrophages and", "and the production", "the production and", "production and maturation", "and maturation of", "maturation of dendritic", "of dendritic cells.", "dendritic cells. it", "cells. it stimulates", "it stimulates myeloblast", "stimulates myeloblast and", "myeloblast and monoblast", "and monoblast differentiation", "differentiation synergises", "synergises with epo", "with epo in", "epo in the", "in the proliferation", "proliferation of erythroid", "of erythroid and", "erythroid and megakaryocytic", "megakaryocytic progenitor", "cells acts", "acts as an", "as an autocrine", "an autocrine mediator", "autocrine mediator of", "mediator of growth", "of growth for", "growth for some", "for some types", "some types of", "types of acute", "of acute myeloid", "acute myeloid leukemia", "leukemia is", "is a strong", "a strong chemoattractant", "strong chemoattractant for", "chemoattractant for neutrophils", "for neutrophils and", "neutrophils and eosinophils.", "and eosinophils. it", "eosinophils. it enhances", "it enhances the", "enhances the activity", "the activity of", "activity of neutrophils", "of neutrophils and", "neutrophils and macrophages.", "and macrophages. under", "macrophages. under steady", "under steady state", "steady state conditions", "state conditions gm", "conditions gm csf", "csf is not", "is not essential", "not essential for", "essential for the", "for the production", "the production of", "production of myeloid", "of myeloid cells", "cells but", "but it is", "it is required", "is required for", "required for the", "for the proper", "the proper development", "proper development of", "development of alveolar", "of alveolar macrophages", "macrophages otherwise", "otherwise pulmonary", "pulmonary alvelolar proteinosis", "proteinosis pap", "pap develops.", "develops. a growing", "a growing body", "growing body of", "body of evidence", "of evidence suggests", "evidence suggests that", "suggests that gm", "that gm csf", "gm csf plays", "csf plays a", "plays a key", "a key role", "key role in", "role in emergency", "in emergency hematopoiesis", "hematopoiesis predominantly", "in response to", "response to infection", "infection including", "including the production", "production of granulocytes", "and macrophages in", "macrophages in the", "in the bone", "the bone marrow", "bone marrow and", "marrow and their", "and their maintenance", "maintenance survival", "survival and", "and functional activation", "functional activation at", "activation at sites", "sites of injury", "of injury or", "injury or insult", "hercus et al.", "et al. 2009", "al. 2009 .

", "2009 .

all", ".

all three", "all three receptors", "three receptors have", "receptors have alpha", "have alpha chains", "alpha chains that", "chains that bind", "that bind their", "bind their specific", "their specific ligands", "specific ligands with", "ligands with low", "with low affinity", "affinity de", "de groot et", "groot et al.", "et al. 1998", "al. 1998 .", "1998 . bc", ". bc then", "bc then associates", "then associates with", "associates with the", "with the alpha", "the alpha chain", "alpha chain forming", "chain forming a", "forming a high", "a high affinity", "high affinity receptor", "receptor geijsen", "geijsen et al.", "et al. 2001", "though the in", "the in vivo", "in vivo receptor", "vivo receptor is", "receptor is likely", "is likely be", "likely be a", "be a higher", "a higher order", "higher order multimer", "order multimer as", "multimer as recently", "as recently demonstrated", "recently demonstrated for", "demonstrated for the", "for the gm", "the gm csf", "gm csf receptor", "receptor hansen", "hansen et al.", "et al. 2008", "al. 2008 .

", "2008 .

the", ".

the receptor", "the receptor chains", "receptor chains lack", "chains lack intrinsic", "lack intrinsic kinase", "intrinsic kinase activity", "activity instead", "instead they interact", "they interact with", "interact with and", "with and activate", "and activate signaling", "activate signaling kinases", "kinases notably", "notably janus kinase", "janus kinase 2", "2 jak2", "jak2 . these", ". these phosphorylate", "these phosphorylate the", "phosphorylate the common", "subunit allowing", "allowing recruitment of", "recruitment of signaling", "of signaling molecules", "signaling molecules such", "molecules such as", "such as shc", "shc the", "the phosphatidylinositol 3", "phosphatidylinositol 3 kinases", "kinases pi3ks", "and the signal", "the signal transducers", "signal transducers and", "transducers and activators", "and activators of", "activators of transcription", "transcription stats", "stats . the", ". the cytoplasmic", "the cytoplasmic domain", "cytoplasmic domain of", "domain of bc", "of bc has", "bc has two", "has two distinct", "two distinct functional", "distinct functional domains:", "functional domains: the", "domains: the membrane", "the membrane proximal", "membrane proximal region", "proximal region mediates", "region mediates the", "mediates the induction", "the induction of", "induction of proliferation", "of proliferation associated", "proliferation associated genes", "associated genes such", "genes such as", "such as c", "as c myc", "myc pim", "pim 1 and", "1 and oncostatin", "and oncostatin m.", "oncostatin m. this", "m. this region", "this region binds", "region binds multiple", "binds multiple signal", "multiple signal transducing", "signal transducing proteins", "transducing proteins including", "proteins including jak2", "jak2 quelle", "quelle et al.", "et al. 1994", "stats c", "c src and", "src and pi3", "and pi3 kinase", "kinase rao", "rao and mufson", "mufson 1995", "1995 . the", ". the membrane", "the membrane distal", "membrane distal domain", "distal domain is", "domain is required", "required for cytokine", "for cytokine induced", "cytokine induced growth", "induced growth inhibition", "growth inhibition and", "inhibition and is", "and is necessary", "is necessary for", "necessary for the", "for the viability", "the viability of", "viability of hematopoietic", "of hematopoietic cells", "cells inhorn", "inhorn et al.", "et al. 1995", "al. 1995 .", "1995 . this", ". this region", "this region interacts", "region interacts with", "interacts with signal", "with signal transducing", "transducing proteins such", "proteins such as", "shc inhorn", "1995 and", "and shp and", "shp and mediates", "and mediates the", "mediates the transcriptional", "the transcriptional activation", "transcriptional activation of", "activation of c", "of c fos", "fos c", "jun c", "c raf and", "raf and p70s6k", "p70s6k reddy", "reddy et al.", "et al. 2000", "al. 2000 .



figure", "2000 .



figure reproduced", ".



figure reproduced by", "reproduced by permission", "by permission from", "permission from macmillan", "from macmillan publishers", "macmillan publishers ltd:", "publishers ltd: leukemia", "leukemia wl", "wl blalock et", "blalock et al.", "et al. 13:1109", "al. 13:1109 1166", "1166 copyright", "copyright 1999. note", "1999. note that", "note that residue", "that residue numbering", "residue numbering in", "numbering in this", "in this diagram", "this diagram refers", "diagram refers to", "refers to the", "to the mature", "the mature common", "mature common beta", "common beta chain", "beta chain with", "chain with signal", "with signal peptide", "signal peptide removed.", "interleukin 3 il", "3 il 3", "il 5 and granulocyte", "5 and granulocyte macrophage", "and granulocyte macrophage colony", "granulocyte macrophage colony stimulating", "macrophage colony stimulating factor", "stimulating factor gm", "factor gm csf", "gm csf receptors", "csf receptors form", "receptors form a family", "form a family of", "a family of heterodimeric", "family of heterodimeric receptors", "of heterodimeric receptors that", "heterodimeric receptors that have", "receptors that have specific", "that have specific alpha", "have specific alpha chains", "specific alpha chains but", "alpha chains but share", "chains but share a", "but share a common", "share a common beta", "a common beta subunit", "beta subunit often", "subunit often referred", "often referred to as", "referred to as the", "to as the common", "as the common beta", "common beta bc", "beta bc .", "bc . both subunits", ". both subunits contain", "both subunits contain extracellular", "subunits contain extracellular conserved", "contain extracellular conserved motifs", "extracellular conserved motifs typical", "conserved motifs typical of", "motifs typical of the", "typical of the cytokine", "of the cytokine receptor", "the cytokine receptor superfamily.", "cytokine receptor superfamily. the", "receptor superfamily. the cytoplasmic", "superfamily. the cytoplasmic domains", "the cytoplasmic domains have", "cytoplasmic domains have limited", "domains have limited similarity", "have limited similarity with", "limited similarity with other", "similarity with other cytokine", "with other cytokine receptors", "other cytokine receptors and", "cytokine receptors and lack", "receptors and lack detectable", "and lack detectable catalytic", "lack detectable catalytic domains", "detectable catalytic domains such", "catalytic domains such as", "domains such as tyrosine", "such as tyrosine kinase", "as tyrosine kinase domains.

", "tyrosine kinase domains.

il", "kinase domains.

il 3", "domains.

il 3 is", "il 3 is a", "3 is a 20", "is a 20 26", "a 20 26 kda", "20 26 kda product", "26 kda product of", "kda product of cd4+", "product of cd4+ t", "of cd4+ t cells", "cd4+ t cells that", "t cells that acts", "cells that acts on", "that acts on the", "acts on the most", "on the most immature", "the most immature marrow", "most immature marrow progenitors.", "immature marrow progenitors. il", "marrow progenitors. il 3", "progenitors. il 3 is", "il 3 is capable", "3 is capable of", "is capable of inducing", "capable of inducing the", "of inducing the growth", "inducing the growth and", "the growth and differentiation", "growth and differentiation of", "and differentiation of multi", "differentiation of multi potential", "of multi potential hematopoietic", "multi potential hematopoietic stem", "potential hematopoietic stem cells", "stem cells neutrophils", "macrophages lymphoid and", "lymphoid and erythroid cells.", "and erythroid cells. il", "erythroid cells. il 3", "cells. il 3 has", "il 3 has been", "3 has been used", "has been used to", "been used to support", "used to support the", "to support the proliferation", "support the proliferation of", "the proliferation of murine", "proliferation of murine cell", "of murine cell lines", "murine cell lines with", "cell lines with properties", "lines with properties of", "with properties of multi", "properties of multi potential", "of multi potential progenitors", "potential progenitors immature", "progenitors immature myeloid", "immature myeloid as well", "myeloid as well as", "as well as t", "well as t and", "as t and pre", "t and pre b", "and pre b lymphoid", "pre b lymphoid cells", "lymphoid cells miyajima", "cells miyajima et", "miyajima et al. 1992", "et al. 1992 .", "al. 1992 . il", "1992 . il 5", ". il 5 is", "il 5 is a", "5 is a hematopoietic", "is a hematopoietic growth", "a hematopoietic growth factor", "hematopoietic growth factor responsible", "growth factor responsible for", "factor responsible for the", "responsible for the maturation", "for the maturation and", "the maturation and differentiation", "maturation and differentiation of", "and differentiation of eosinophils.", "differentiation of eosinophils. it", "of eosinophils. it was", "eosinophils. it was originally", "it was originally defined", "was originally defined as", "originally defined as a", "defined as a t", "as a t cell", "a t cell derived", "t cell derived cytokine", "cell derived cytokine that", "derived cytokine that triggers", "cytokine that triggers activated", "that triggers activated b", "triggers activated b cells", "activated b cells for", "b cells for terminal", "cells for terminal differentiation", "for terminal differentiation into", "terminal differentiation into antibody", "differentiation into antibody secreting", "into antibody secreting plasma", "antibody secreting plasma cells.", "secreting plasma cells. it", "plasma cells. it also", "cells. it also promotes", "it also promotes the", "also promotes the generation", "promotes the generation of", "the generation of cytotoxic", "generation of cytotoxic t", "of cytotoxic t cells", "cytotoxic t cells from", "t cells from thymocytes.", "cells from thymocytes. il", "from thymocytes. il 5", "thymocytes. il 5 induces", "il 5 induces the", "5 induces the expression", "induces the expression of", "the expression of il", "expression of il 2", "of il 2 receptors", "2 receptors kouro", "receptors kouro &", "kouro & takatsu 2009", "& takatsu 2009 .", "takatsu 2009 . gm", "2009 . gm csf", ". gm csf is", "gm csf is produced", "csf is produced by", "is produced by cells", "by cells t", "cells t lymphocytes", "t lymphocytes tissue", "lymphocytes tissue macrophages", "tissue macrophages endothelial", "macrophages endothelial cells", "endothelial cells mast", "cells mast cells", "mast cells found", "cells found at", "found at sites of", "at sites of inflammatory", "sites of inflammatory responses.", "of inflammatory responses. it", "inflammatory responses. it stimulates", "responses. it stimulates the", "it stimulates the growth", "stimulates the growth and", "the growth and development", "growth and development of", "and development of progenitors", "development of progenitors of", "of progenitors of granulocytes", "progenitors of granulocytes and", "of granulocytes and macrophages", "and macrophages and", "macrophages and the", "and the production and", "the production and maturation", "production and maturation of", "and maturation of dendritic", "maturation of dendritic cells.", "of dendritic cells. it", "dendritic cells. it stimulates", "cells. it stimulates myeloblast", "it stimulates myeloblast and", "stimulates myeloblast and monoblast", "myeloblast and monoblast differentiation", "monoblast differentiation synergises", "differentiation synergises with", "synergises with epo in", "with epo in the", "epo in the proliferation", "in the proliferation of", "the proliferation of erythroid", "proliferation of erythroid and", "of erythroid and megakaryocytic", "and megakaryocytic progenitor", "megakaryocytic progenitor cells", "progenitor cells acts", "cells acts as", "acts as an autocrine", "as an autocrine mediator", "an autocrine mediator of", "autocrine mediator of growth", "mediator of growth for", "of growth for some", "growth for some types", "for some types of", "some types of acute", "types of acute myeloid", "of acute myeloid leukemia", "myeloid leukemia is", "leukemia is a", "is a strong chemoattractant", "a strong chemoattractant for", "strong chemoattractant for neutrophils", "chemoattractant for neutrophils and", "for neutrophils and eosinophils.", "neutrophils and eosinophils. it", "and eosinophils. it enhances", "eosinophils. it enhances the", "it enhances the activity", "enhances the activity of", "the activity of neutrophils", "activity of neutrophils and", "of neutrophils and macrophages.", "neutrophils and macrophages. under", "and macrophages. under steady", "macrophages. under steady state", "under steady state conditions", "steady state conditions gm", "state conditions gm csf", "conditions gm csf is", "gm csf is not", "csf is not essential", "is not essential for", "not essential for the", "essential for the production", "for the production of", "the production of myeloid", "production of myeloid cells", "myeloid cells but", "cells but it", "but it is required", "it is required for", "is required for the", "required for the proper", "for the proper development", "the proper development of", "proper development of alveolar", "development of alveolar macrophages", "alveolar macrophages otherwise", "otherwise pulmonary alvelolar", "alvelolar proteinosis pap", "pap develops. a", "develops. a growing body", "a growing body of", "growing body of evidence", "body of evidence suggests", "of evidence suggests that", "evidence suggests that gm", "suggests that gm csf", "that gm csf plays", "gm csf plays a", "csf plays a key", "plays a key role", "a key role in", "key role in emergency", "role in emergency hematopoiesis", "emergency hematopoiesis predominantly", "hematopoiesis predominantly myelopoiesis", "myelopoiesis in", "in response to infection", "to infection including", "infection including the", "including the production of", "the production of granulocytes", "production of granulocytes and", "granulocytes and macrophages in", "and macrophages in the", "macrophages in the bone", "in the bone marrow", "the bone marrow and", "bone marrow and their", "marrow and their maintenance", "their maintenance survival", "survival and functional", "and functional activation at", "functional activation at sites", "activation at sites of", "at sites of injury", "sites of injury or", "of injury or insult", "insult hercus", "hercus et al. 2009", "et al. 2009 .

", "al. 2009 .

all", "2009 .

all three", ".

all three receptors", "all three receptors have", "three receptors have alpha", "receptors have alpha chains", "have alpha chains that", "alpha chains that bind", "chains that bind their", "that bind their specific", "bind their specific ligands", "their specific ligands with", "specific ligands with low", "ligands with low affinity", "low affinity de", "affinity de groot", "de groot et al.", "groot et al. 1998", "et al. 1998 .", "al. 1998 . bc", "1998 . bc then", ". bc then associates", "bc then associates with", "then associates with the", "associates with the alpha", "with the alpha chain", "the alpha chain forming", "alpha chain forming a", "chain forming a high", "forming a high affinity", "a high affinity receptor", "affinity receptor geijsen", "receptor geijsen et", "geijsen et al. 2001", "2001 though", "though the in vivo", "the in vivo receptor", "in vivo receptor is", "vivo receptor is likely", "receptor is likely be", "is likely be a", "likely be a higher", "be a higher order", "a higher order multimer", "higher order multimer as", "order multimer as recently", "multimer as recently demonstrated", "as recently demonstrated for", "recently demonstrated for the", "demonstrated for the gm", "for the gm csf", "the gm csf receptor", "csf receptor hansen", "receptor hansen et", "hansen et al. 2008", "et al. 2008 .

", "al. 2008 .

the", "2008 .

the receptor", ".

the receptor chains", "the receptor chains lack", "receptor chains lack intrinsic", "chains lack intrinsic kinase", "lack intrinsic kinase activity", "kinase activity instead", "activity instead they", "instead they interact with", "they interact with and", "interact with and activate", "with and activate signaling", "and activate signaling kinases", "signaling kinases notably", "kinases notably janus", "notably janus kinase 2", "kinase 2 jak2", "2 jak2 .", "jak2 . these phosphorylate", ". these phosphorylate the", "these phosphorylate the common", "phosphorylate the common beta", "the common beta subunit", "beta subunit allowing", "subunit allowing recruitment", "allowing recruitment of signaling", "recruitment of signaling molecules", "of signaling molecules such", "signaling molecules such as", "molecules such as shc", "as shc the", "shc the phosphatidylinositol", "the phosphatidylinositol 3 kinases", "3 kinases pi3ks", "pi3ks and", "and the signal transducers", "the signal transducers and", "signal transducers and activators", "transducers and activators of", "and activators of transcription", "of transcription stats", "transcription stats .", "stats . the cytoplasmic", ". the cytoplasmic domain", "the cytoplasmic domain of", "cytoplasmic domain of bc", "domain of bc has", "of bc has two", "bc has two distinct", "has two distinct functional", "two distinct functional domains:", "distinct functional domains: the", "functional domains: the membrane", "domains: the membrane proximal", "the membrane proximal region", "membrane proximal region mediates", "proximal region mediates the", "region mediates the induction", "mediates the induction of", "the induction of proliferation", "induction of proliferation associated", "of proliferation associated genes", "proliferation associated genes such", "associated genes such as", "genes such as c", "such as c myc", "c myc pim", "myc pim 1", "pim 1 and oncostatin", "1 and oncostatin m.", "and oncostatin m. this", "oncostatin m. this region", "m. this region binds", "this region binds multiple", "region binds multiple signal", "binds multiple signal transducing", "multiple signal transducing proteins", "signal transducing proteins including", "transducing proteins including jak2", "including jak2 quelle", "jak2 quelle et", "quelle et al. 1994", "1994 stats", "stats c src", "c src and pi3", "src and pi3 kinase", "pi3 kinase rao", "kinase rao and", "and mufson 1995", "mufson 1995 .", "1995 . the membrane", ". the membrane distal", "the membrane distal domain", "membrane distal domain is", "distal domain is required", "domain is required for", "is required for cytokine", "required for cytokine induced", "for cytokine induced growth", "cytokine induced growth inhibition", "induced growth inhibition and", "growth inhibition and is", "inhibition and is necessary", "and is necessary for", "is necessary for the", "necessary for the viability", "for the viability of", "the viability of hematopoietic", "viability of hematopoietic cells", "hematopoietic cells inhorn", "cells inhorn et", "inhorn et al. 1995", "et al. 1995 .", "al. 1995 . this", "1995 . this region", ". this region interacts", "this region interacts with", "region interacts with signal", "interacts with signal transducing", "with signal transducing proteins", "signal transducing proteins such", "transducing proteins such as", "proteins such as shc", "as shc inhorn", "shc inhorn et", "al. 1995 and", "1995 and shp", "and shp and mediates", "shp and mediates the", "and mediates the transcriptional", "mediates the transcriptional activation", "the transcriptional activation of", "transcriptional activation of c", "activation of c fos", "c fos c", "fos c jun", "c jun c", "jun c raf", "c raf and p70s6k", "and p70s6k reddy", "p70s6k reddy et", "reddy et al. 2000", "et al. 2000 .



figure", "al. 2000 .



figure reproduced", "2000 .



figure reproduced by", ".



figure reproduced by permission", "reproduced by permission from", "by permission from macmillan", "permission from macmillan publishers", "from macmillan publishers ltd:", "macmillan publishers ltd: leukemia", "ltd: leukemia wl", "leukemia wl blalock", "wl blalock et al.", "blalock et al. 13:1109", "et al. 13:1109 1166", "13:1109 1166 copyright", "1166 copyright 1999.", "copyright 1999. note that", "1999. note that residue", "note that residue numbering", "that residue numbering in", "residue numbering in this", "numbering in this diagram", "in this diagram refers", "this diagram refers to", "diagram refers to the", "refers to the mature", "to the mature common", "the mature common beta", "mature common beta chain", "common beta chain with", "beta chain with signal", "chain with signal peptide", "with signal peptide removed.", "the interleukin 3 il", "interleukin 3 il 3", "il 3 il", "3 il 5", "il 5 and granulocyte macrophage", "5 and granulocyte macrophage colony", "and granulocyte macrophage colony stimulating", "granulocyte macrophage colony stimulating factor", "colony stimulating factor gm", "stimulating factor gm csf", "gm csf receptors form", "csf receptors form a", "receptors form a family of", "form a family of heterodimeric", "a family of heterodimeric receptors", "family of heterodimeric receptors that", "of heterodimeric receptors that have", "heterodimeric receptors that have specific", "receptors that have specific alpha", "that have specific alpha chains", "have specific alpha chains but", "specific alpha chains but share", "alpha chains but share a", "chains but share a common", "but share a common beta", "share a common beta subunit", "common beta subunit often", "beta subunit often referred", "subunit often referred to", "often referred to as the", "referred to as the common", "to as the common beta", "the common beta bc", "common beta bc .", "beta bc . both", "bc . both subunits contain", ". both subunits contain extracellular", "both subunits contain extracellular conserved", "subunits contain extracellular conserved motifs", "contain extracellular conserved motifs typical", "extracellular conserved motifs typical of", "conserved motifs typical of the", "motifs typical of the cytokine", "typical of the cytokine receptor", "of the cytokine receptor superfamily.", "the cytokine receptor superfamily. the", "cytokine receptor superfamily. the cytoplasmic", "receptor superfamily. the cytoplasmic domains", "superfamily. the cytoplasmic domains have", "the cytoplasmic domains have limited", "cytoplasmic domains have limited similarity", "domains have limited similarity with", "have limited similarity with other", "limited similarity with other cytokine", "similarity with other cytokine receptors", "with other cytokine receptors and", "other cytokine receptors and lack", "cytokine receptors and lack detectable", "receptors and lack detectable catalytic", "and lack detectable catalytic domains", "lack detectable catalytic domains such", "detectable catalytic domains such as", "catalytic domains such as tyrosine", "domains such as tyrosine kinase", "such as tyrosine kinase domains.

", "as tyrosine kinase domains.

il", "tyrosine kinase domains.

il 3", "kinase domains.

il 3 is", "domains.

il 3 is a", "il 3 is a 20", "3 is a 20 26", "is a 20 26 kda", "a 20 26 kda product", "20 26 kda product of", "26 kda product of cd4+", "kda product of cd4+ t", "product of cd4+ t cells", "of cd4+ t cells that", "cd4+ t cells that acts", "t cells that acts on", "cells that acts on the", "that acts on the most", "acts on the most immature", "on the most immature marrow", "the most immature marrow progenitors.", "most immature marrow progenitors. il", "immature marrow progenitors. il 3", "marrow progenitors. il 3 is", "progenitors. il 3 is capable", "il 3 is capable of", "3 is capable of inducing", "is capable of inducing the", "capable of inducing the growth", "of inducing the growth and", "inducing the growth and differentiation", "the growth and differentiation of", "growth and differentiation of multi", "and differentiation of multi potential", "differentiation of multi potential hematopoietic", "of multi potential hematopoietic stem", "multi potential hematopoietic stem cells", "hematopoietic stem cells neutrophils", "cells neutrophils eosinophils", "neutrophils eosinophils megakaryocytes", "eosinophils megakaryocytes macrophages", "megakaryocytes macrophages lymphoid", "macrophages lymphoid and erythroid", "lymphoid and erythroid cells. il", "and erythroid cells. il 3", "erythroid cells. il 3 has", "cells. il 3 has been", "il 3 has been used", "3 has been used to", "has been used to support", "been used to support the", "used to support the proliferation", "to support the proliferation of", "support the proliferation of murine", "the proliferation of murine cell", "proliferation of murine cell lines", "of murine cell lines with", "murine cell lines with properties", "cell lines with properties of", "lines with properties of multi", "with properties of multi potential", "properties of multi potential progenitors", "multi potential progenitors immature", "potential progenitors immature myeloid", "progenitors immature myeloid as", "immature myeloid as well as", "myeloid as well as t", "as well as t and", "well as t and pre", "as t and pre b", "t and pre b lymphoid", "and pre b lymphoid cells", "b lymphoid cells miyajima", "lymphoid cells miyajima et", "cells miyajima et al.", "miyajima et al. 1992 .", "et al. 1992 . il", "al. 1992 . il 5", "1992 . il 5 is", ". il 5 is a", "il 5 is a hematopoietic", "5 is a hematopoietic growth", "is a hematopoietic growth factor", "a hematopoietic growth factor responsible", "hematopoietic growth factor responsible for", "growth factor responsible for the", "factor responsible for the maturation", "responsible for the maturation and", "for the maturation and differentiation", "the maturation and differentiation of", "maturation and differentiation of eosinophils.", "and differentiation of eosinophils. it", "differentiation of eosinophils. it was", "of eosinophils. it was originally", "eosinophils. it was originally defined", "it was originally defined as", "was originally defined as a", "originally defined as a t", "defined as a t cell", "as a t cell derived", "a t cell derived cytokine", "t cell derived cytokine that", "cell derived cytokine that triggers", "derived cytokine that triggers activated", "cytokine that triggers activated b", "that triggers activated b cells", "triggers activated b cells for", "activated b cells for terminal", "b cells for terminal differentiation", "cells for terminal differentiation into", "for terminal differentiation into antibody", "terminal differentiation into antibody secreting", "differentiation into antibody secreting plasma", "into antibody secreting plasma cells.", "antibody secreting plasma cells. it", "secreting plasma cells. it also", "plasma cells. it also promotes", "cells. it also promotes the", "it also promotes the generation", "also promotes the generation of", "promotes the generation of cytotoxic", "the generation of cytotoxic t", "generation of cytotoxic t cells", "of cytotoxic t cells from", "cytotoxic t cells from thymocytes.", "t cells from thymocytes. il", "cells from thymocytes. il 5", "from thymocytes. il 5 induces", "thymocytes. il 5 induces the", "il 5 induces the expression", "5 induces the expression of", "induces the expression of il", "the expression of il 2", "expression of il 2 receptors", "il 2 receptors kouro", "2 receptors kouro &", "receptors kouro & takatsu", "kouro & takatsu 2009 .", "& takatsu 2009 . gm", "takatsu 2009 . gm csf", "2009 . gm csf is", ". gm csf is produced", "gm csf is produced by", "csf is produced by cells", "produced by cells t", "by cells t lymphocytes", "t lymphocytes tissue macrophages", "tissue macrophages endothelial cells", "endothelial cells mast cells", "mast cells found at", "cells found at sites", "found at sites of inflammatory", "at sites of inflammatory responses.", "sites of inflammatory responses. it", "of inflammatory responses. it stimulates", "inflammatory responses. it stimulates the", "responses. it stimulates the growth", "it stimulates the growth and", "stimulates the growth and development", "the growth and development of", "growth and development of progenitors", "and development of progenitors of", "development of progenitors of granulocytes", "of progenitors of granulocytes and", "progenitors of granulocytes and macrophages", "granulocytes and macrophages and", "and macrophages and the", "macrophages and the production", "and the production and maturation", "the production and maturation of", "production and maturation of dendritic", "and maturation of dendritic cells.", "maturation of dendritic cells. it", "of dendritic cells. it stimulates", "dendritic cells. it stimulates myeloblast", "cells. it stimulates myeloblast and", "it stimulates myeloblast and monoblast", "stimulates myeloblast and monoblast differentiation", "and monoblast differentiation synergises", "monoblast differentiation synergises with", "differentiation synergises with epo", "synergises with epo in the", "with epo in the proliferation", "epo in the proliferation of", "in the proliferation of erythroid", "the proliferation of erythroid and", "proliferation of erythroid and megakaryocytic", "erythroid and megakaryocytic progenitor", "and megakaryocytic progenitor cells", "progenitor cells acts as", "cells acts as an", "acts as an autocrine mediator", "as an autocrine mediator of", "an autocrine mediator of growth", "autocrine mediator of growth for", "mediator of growth for some", "of growth for some types", "growth for some types of", "for some types of acute", "some types of acute myeloid", "types of acute myeloid leukemia", "acute myeloid leukemia is", "myeloid leukemia is a", "leukemia is a strong", "is a strong chemoattractant for", "a strong chemoattractant for neutrophils", "strong chemoattractant for neutrophils and", "chemoattractant for neutrophils and eosinophils.", "for neutrophils and eosinophils. it", "neutrophils and eosinophils. it enhances", "and eosinophils. it enhances the", "eosinophils. it enhances the activity", "it enhances the activity of", "enhances the activity of neutrophils", "the activity of neutrophils and", "activity of neutrophils and macrophages.", "of neutrophils and macrophages. under", "neutrophils and macrophages. under steady", "and macrophages. under steady state", "macrophages. under steady state conditions", "under steady state conditions gm", "steady state conditions gm csf", "state conditions gm csf is", "conditions gm csf is not", "gm csf is not essential", "csf is not essential for", "is not essential for the", "not essential for the production", "essential for the production of", "for the production of myeloid", "the production of myeloid cells", "of myeloid cells but", "myeloid cells but it", "cells but it is", "but it is required for", "it is required for the", "is required for the proper", "required for the proper development", "for the proper development of", "the proper development of alveolar", "proper development of alveolar macrophages", "of alveolar macrophages otherwise", "macrophages otherwise pulmonary", "otherwise pulmonary alvelolar proteinosis", "pulmonary alvelolar proteinosis pap", "proteinosis pap develops.", "pap develops. a growing", "develops. a growing body of", "a growing body of evidence", "growing body of evidence suggests", "body of evidence suggests that", "of evidence suggests that gm", "evidence suggests that gm csf", "suggests that gm csf plays", "that gm csf plays a", "gm csf plays a key", "csf plays a key role", "plays a key role in", "a key role in emergency", "key role in emergency hematopoiesis", "in emergency hematopoiesis predominantly", "emergency hematopoiesis predominantly myelopoiesis", "predominantly myelopoiesis in", "myelopoiesis in response", "response to infection including", "to infection including the", "infection including the production", "including the production of granulocytes", "the production of granulocytes and", "production of granulocytes and macrophages", "of granulocytes and macrophages in", "granulocytes and macrophages in the", "and macrophages in the bone", "macrophages in the bone marrow", "in the bone marrow and", "the bone marrow and their", "bone marrow and their maintenance", "and their maintenance survival", "maintenance survival and", "survival and functional activation", "and functional activation at sites", "functional activation at sites of", "activation at sites of injury", "at sites of injury or", "sites of injury or insult", "or insult hercus", "insult hercus et", "hercus et al. 2009 .

", "et al. 2009 .

all", "al. 2009 .

all three", "2009 .

all three receptors", ".

all three receptors have", "all three receptors have alpha", "three receptors have alpha chains", "receptors have alpha chains that", "have alpha chains that bind", "alpha chains that bind their", "chains that bind their specific", "that bind their specific ligands", "bind their specific ligands with", "their specific ligands with low", "specific ligands with low affinity", "with low affinity de", "low affinity de groot", "affinity de groot et", "de groot et al. 1998", "groot et al. 1998 .", "et al. 1998 . bc", "al. 1998 . bc then", "1998 . bc then associates", ". bc then associates with", "bc then associates with the", "then associates with the alpha", "associates with the alpha chain", "with the alpha chain forming", "the alpha chain forming a", "alpha chain forming a high", "chain forming a high affinity", "forming a high affinity receptor", "high affinity receptor geijsen", "affinity receptor geijsen et", "receptor geijsen et al.", "al. 2001 though", "2001 though the", "though the in vivo receptor", "the in vivo receptor is", "in vivo receptor is likely", "vivo receptor is likely be", "receptor is likely be a", "is likely be a higher", "likely be a higher order", "be a higher order multimer", "a higher order multimer as", "higher order multimer as recently", "order multimer as recently demonstrated", "multimer as recently demonstrated for", "as recently demonstrated for the", "recently demonstrated for the gm", "demonstrated for the gm csf", "for the gm csf receptor", "gm csf receptor hansen", "csf receptor hansen et", "receptor hansen et al.", "hansen et al. 2008 .

", "et al. 2008 .

the", "al. 2008 .

the receptor", "2008 .

the receptor chains", ".

the receptor chains lack", "the receptor chains lack intrinsic", "receptor chains lack intrinsic kinase", "chains lack intrinsic kinase activity", "intrinsic kinase activity instead", "kinase activity instead they", "activity instead they interact", "instead they interact with and", "they interact with and activate", "interact with and activate signaling", "with and activate signaling kinases", "activate signaling kinases notably", "signaling kinases notably janus", "kinases notably janus kinase", "janus kinase 2 jak2", "kinase 2 jak2 .", "2 jak2 . these", "jak2 . these phosphorylate the", ". these phosphorylate the common", "these phosphorylate the common beta", "phosphorylate the common beta subunit", "common beta subunit allowing", "beta subunit allowing recruitment", "subunit allowing recruitment of", "allowing recruitment of signaling molecules", "recruitment of signaling molecules such", "of signaling molecules such as", "signaling molecules such as shc", "such as shc the", "as shc the phosphatidylinositol", "shc the phosphatidylinositol 3", "phosphatidylinositol 3 kinases pi3ks", "pi3ks and the", "and the signal transducers and", "the signal transducers and activators", "signal transducers and activators of", "transducers and activators of transcription", "activators of transcription stats", "of transcription stats .", "transcription stats . the", "stats . the cytoplasmic domain", ". the cytoplasmic domain of", "the cytoplasmic domain of bc", "cytoplasmic domain of bc has", "domain of bc has two", "of bc has two distinct", "bc has two distinct functional", "has two distinct functional domains:", "two distinct functional domains: the", "distinct functional domains: the membrane", "functional domains: the membrane proximal", "domains: the membrane proximal region", "the membrane proximal region mediates", "membrane proximal region mediates the", "proximal region mediates the induction", "region mediates the induction of", "mediates the induction of proliferation", "the induction of proliferation associated", "induction of proliferation associated genes", "of proliferation associated genes such", "proliferation associated genes such as", "associated genes such as c", "genes such as c myc", "as c myc pim", "c myc pim 1", "myc pim 1 and", "pim 1 and oncostatin m.", "1 and oncostatin m. this", "and oncostatin m. this region", "oncostatin m. this region binds", "m. this region binds multiple", "this region binds multiple signal", "region binds multiple signal transducing", "binds multiple signal transducing proteins", "multiple signal transducing proteins including", "signal transducing proteins including jak2", "proteins including jak2 quelle", "including jak2 quelle et", "jak2 quelle et al.", "al. 1994 stats", "stats c src and", "c src and pi3 kinase", "and pi3 kinase rao", "pi3 kinase rao and", "kinase rao and mufson", "rao and mufson 1995", "and mufson 1995 .", "mufson 1995 . the", "1995 . the membrane distal", ". the membrane distal domain", "the membrane distal domain is", "membrane distal domain is required", "distal domain is required for", "domain is required for cytokine", "is required for cytokine induced", "required for cytokine induced growth", "for cytokine induced growth inhibition", "cytokine induced growth inhibition and", "induced growth inhibition and is", "growth inhibition and is necessary", "inhibition and is necessary for", "and is necessary for the", "is necessary for the viability", "necessary for the viability of", "for the viability of hematopoietic", "the viability of hematopoietic cells", "of hematopoietic cells inhorn", "hematopoietic cells inhorn et", "cells inhorn et al.", "inhorn et al. 1995 .", "et al. 1995 . this", "al. 1995 . this region", "1995 . this region interacts", ". this region interacts with", "this region interacts with signal", "region interacts with signal transducing", "interacts with signal transducing proteins", "with signal transducing proteins such", "signal transducing proteins such as", "transducing proteins such as shc", "such as shc inhorn", "as shc inhorn et", "shc inhorn et al.", "et al. 1995 and", "al. 1995 and shp", "1995 and shp and", "and shp and mediates the", "shp and mediates the transcriptional", "and mediates the transcriptional activation", "mediates the transcriptional activation of", "the transcriptional activation of c", "transcriptional activation of c fos", "of c fos c", "c fos c jun", "c jun c raf", "jun c raf and", "raf and p70s6k reddy", "and p70s6k reddy et", "p70s6k reddy et al.", "reddy et al. 2000 .



figure", "et al. 2000 .



figure reproduced", "al. 2000 .



figure reproduced by", "2000 .



figure reproduced by permission", ".



figure reproduced by permission from", "reproduced by permission from macmillan", "by permission from macmillan publishers", "permission from macmillan publishers ltd:", "from macmillan publishers ltd: leukemia", "publishers ltd: leukemia wl", "ltd: leukemia wl blalock", "leukemia wl blalock et", "wl blalock et al. 13:1109", "blalock et al. 13:1109 1166", "al. 13:1109 1166 copyright", "13:1109 1166 copyright 1999.", "1166 copyright 1999. note", "copyright 1999. note that residue", "1999. note that residue numbering", "note that residue numbering in", "that residue numbering in this", "residue numbering in this diagram", "numbering in this diagram refers", "in this diagram refers to", "this diagram refers to the", "diagram refers to the mature", "refers to the mature common", "to the mature common beta", "the mature common beta chain", "mature common beta chain with", "common beta chain with signal", "beta chain with signal peptide", "chain with signal peptide removed." ] }, { "record_id": "GLY_000594_1_408", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5173214", "r hsa", "hsa 5173214", "r hsa 5173214" ] }, { "record_id": "GLY_000594_1_408", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "o glycosylation", "glycosylation of", "of tsr", "tsr domain", "domain containing", "containing proteins", "o glycosylation of", "glycosylation of tsr", "of tsr domain", "tsr domain containing", "domain containing proteins", "o glycosylation of tsr", "glycosylation of tsr domain", "of tsr domain containing", "tsr domain containing proteins", "o glycosylation of tsr domain", "glycosylation of tsr domain containing", "of tsr domain containing proteins", "the o", "o fucosylation", "fucosylation of", "of proteins", "proteins containing", "containing thrombospondin", "thrombospondin type", "type 1", "1 repeat", "domains is", "is an", "an important", "important ptm", "regulating many", "many biological", "biological processes", "processes such", "such as", "as notch", "notch signalling", "wound healing", "angiogenesis amd", "amd neoplasia", "adams &", "& tucker", "tucker 2000", "moremen et", "et al.", "al. 2012", "2012 .", ". fucose", "fucose addition", "addition is", "is carried", "carried out", "out by", "by two", "two protein", "protein fucosyltransferases", "pofut1 and", "and 2.", "2. only", "only pofut2", "pofut2 recognises", "recognises the", "the consensus", "consensus sequence", "sequence csxs/tcg", "csxs/tcg found", "found in", "in tsr1", "tsr1 domains", "domains and", "and the", "the fucosyl", "fucosyl residue", "residue is", "is attached", "attached to", "to the", "the hydroxyl", "hydroxyl group", "group of", "of conserved", "conserved serine", "or threonine", "residues within", "within the", "consensus sequence.", "sequence. the", "the modification", "modification was", "was first", "first demonstrated", "demonstrated on", "on thrombospondin", "thrombospondin 1", "in platelets", "platelets and", "the ecm", "hofsteenge et", "al. 2001", "luo et", "al. 2006", "2006 .", ". the", "the resulting", "resulting o", "o fucosyl", "fucosyl protein", "protein is", "is subsequently", "subsequently a", "a substrate", "substrate for", "for beta", "beta 1", "1 3", "3 glucosyltransferase", "glucosyltransferase like", "like protein", "which adds", "adds a", "a glucosyl", "glucosyl moiety", "moiety to", "to form", "form the", "the rare", "rare disaccharide", "disaccharide modification", "modification glc", "glc beta", "3 fuc.", "fuc. more", "more than", "than 60", "60 human", "human proteins", "proteins contain", "contain tsr1", "the disaccharide", "modification has", "has been", "been demonstrated", "on a", "a small", "small number", "number of", "of these", "these tsr1", "tsr1 domain", "proteins such", "as thrombospondin", "gonzalez de", "de peredo", "peredo et", "al. 2002", "and f", "f spondin", "2002 .", "the adamts", "a disintegrin", "disintegrin like", "like and", "and metalloprotease", "metalloprotease domain", "domain with", "with thrombospondin", "1 repeats", "superfamily consists", "consists of", "of 19", "19 secreted", "secreted metalloproteases", "adamts proteases", "and at", "at lease", "lease five", "five adamts", "adamts like", "like proteins", "proteins in", "in humans.", "humans. five", "five members", "members of", "of the", "adamts superfamily", "superfamily have", "have also", "also had", "had experimental", "experimental confirmation", "confirmation of", "disaccharide modification.", "modification. examples", "examples are", "are adamts13", "ricketts et", "al. 2007", "and adamtsl1", "wang et", "2007 .", ". in", "in the", "the two", "two reactions", "reactions described", "described here", "the tsr1", "proteins with", "with similarity", "similarity to", "the experimentally", "experimentally confirmed", "confirmed ones", "ones are", "are included", "included as", "as putative", "putative substrates.", "the o fucosylation", "o fucosylation of", "fucosylation of proteins", "of proteins containing", "proteins containing thrombospondin", "containing thrombospondin type", "thrombospondin type 1", "type 1 repeat", "repeat tsr", "tsr domains", "domains is an", "is an important", "an important ptm", "ptm regulating", "regulating many biological", "many biological processes", "biological processes such", "processes such as", "such as notch", "as notch signalling", "signalling inflammation", "inflammation wound", "healing angiogenesis", "angiogenesis amd neoplasia", "neoplasia adams", "adams & tucker", "& tucker 2000", "2000 moremen", "moremen et al.", "et al. 2012", "al. 2012 .", "2012 . fucose", ". fucose addition", "fucose addition is", "addition is carried", "is carried out", "carried out by", "out by two", "by two protein", "two protein fucosyltransferases", "fucosyltransferases pofut1", "pofut1 and 2.", "and 2. only", "2. only pofut2", "only pofut2 recognises", "pofut2 recognises the", "recognises the consensus", "the consensus sequence", "consensus sequence csxs/tcg", "sequence csxs/tcg found", "csxs/tcg found in", "found in tsr1", "in tsr1 domains", "tsr1 domains and", "domains and the", "and the fucosyl", "the fucosyl residue", "fucosyl residue is", "residue is attached", "is attached to", "attached to the", "to the hydroxyl", "the hydroxyl group", "hydroxyl group of", "group of conserved", "of conserved serine", "serine s", "s or", "threonine t", "t residues", "residues within the", "within the consensus", "the consensus sequence.", "consensus sequence. the", "sequence. the modification", "the modification was", "modification was first", "was first demonstrated", "first demonstrated on", "demonstrated on thrombospondin", "on thrombospondin 1", "1 found", "found in platelets", "in platelets and", "platelets and the", "and the ecm", "ecm hofsteenge", "hofsteenge et al.", "et al. 2001", "2001 luo", "luo et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the resulting", "the resulting o", "resulting o fucosyl", "o fucosyl protein", "fucosyl protein is", "protein is subsequently", "is subsequently a", "subsequently a substrate", "a substrate for", "substrate for beta", "for beta 1", "beta 1 3", "1 3 glucosyltransferase", "3 glucosyltransferase like", "glucosyltransferase like protein", "protein b3galtl", "which adds a", "adds a glucosyl", "a glucosyl moiety", "glucosyl moiety to", "moiety to form", "to form the", "form the rare", "the rare disaccharide", "rare disaccharide modification", "disaccharide modification glc", "modification glc beta", "glc beta 1", "1 3 fuc.", "3 fuc. more", "fuc. more than", "more than 60", "than 60 human", "60 human proteins", "human proteins contain", "proteins contain tsr1", "contain tsr1 domains", "domains the", "the disaccharide modification", "disaccharide modification has", "modification has been", "has been demonstrated", "been demonstrated on", "demonstrated on a", "on a small", "a small number", "small number of", "number of these", "of these tsr1", "these tsr1 domain", "tsr1 domain containing", "containing proteins such", "proteins such as", "such as thrombospondin", "as thrombospondin 1", "1 hofsteenge", "properdin gonzalez", "gonzalez de peredo", "de peredo et", "peredo et al.", "et al. 2002", "2002 and", "and f spondin", "spondin gonzalez", "al. 2002 .", "2002 . the", ". the adamts", "adamts a", "a disintegrin like", "disintegrin like and", "like and metalloprotease", "and metalloprotease domain", "metalloprotease domain with", "domain with thrombospondin", "with thrombospondin type", "type 1 repeats", "repeats superfamily", "superfamily consists of", "consists of 19", "of 19 secreted", "19 secreted metalloproteases", "metalloproteases adamts", "proteases and", "and at lease", "at lease five", "lease five adamts", "five adamts like", "adamts like proteins", "like proteins in", "proteins in humans.", "in humans. five", "humans. five members", "five members of", "members of the", "of the adamts", "the adamts superfamily", "adamts superfamily have", "superfamily have also", "have also had", "also had experimental", "had experimental confirmation", "experimental confirmation of", "confirmation of the", "of the disaccharide", "the disaccharide modification.", "disaccharide modification. examples", "modification. examples are", "examples are adamts13", "adamts13 ricketts", "ricketts et al.", "et al. 2007", "2007 and", "adamtsl1 wang", "wang et al.", "al. 2007 .", "2007 . in", ". in the", "in the two", "the two reactions", "two reactions described", "reactions described here", "here the", "the tsr1 domain", "containing proteins with", "proteins with similarity", "with similarity to", "similarity to the", "to the experimentally", "the experimentally confirmed", "experimentally confirmed ones", "confirmed ones are", "ones are included", "are included as", "included as putative", "as putative substrates.", "the o fucosylation of", "o fucosylation of proteins", "fucosylation of proteins containing", "of proteins containing thrombospondin", "proteins containing thrombospondin type", "containing thrombospondin type 1", "thrombospondin type 1 repeat", "1 repeat tsr", "tsr domains is", "domains is an important", "is an important ptm", "important ptm regulating", "ptm regulating many", "regulating many biological processes", "many biological processes such", "biological processes such as", "processes such as notch", "such as notch signalling", "notch signalling inflammation", "inflammation wound healing", "wound healing angiogenesis", "healing angiogenesis amd", "amd neoplasia adams", "neoplasia adams &", "adams & tucker 2000", "tucker 2000 moremen", "2000 moremen et", "moremen et al. 2012", "et al. 2012 .", "al. 2012 . fucose", "2012 . fucose addition", ". fucose addition is", "fucose addition is carried", "addition is carried out", "is carried out by", "carried out by two", "out by two protein", "by two protein fucosyltransferases", "protein fucosyltransferases pofut1", "fucosyltransferases pofut1 and", "pofut1 and 2. only", "and 2. only pofut2", "2. only pofut2 recognises", "only pofut2 recognises the", "pofut2 recognises the consensus", "recognises the consensus sequence", "the consensus sequence csxs/tcg", "consensus sequence csxs/tcg found", "sequence csxs/tcg found in", "csxs/tcg found in tsr1", "found in tsr1 domains", "in tsr1 domains and", "tsr1 domains and the", "domains and the fucosyl", "and the fucosyl residue", "the fucosyl residue is", "fucosyl residue is attached", "residue is attached to", "is attached to the", "attached to the hydroxyl", "to the hydroxyl group", "the hydroxyl group of", "hydroxyl group of conserved", "group of conserved serine", "conserved serine s", "s or threonine", "or threonine t", "t residues within", "residues within the consensus", "within the consensus sequence.", "the consensus sequence. the", "consensus sequence. the modification", "sequence. the modification was", "the modification was first", "modification was first demonstrated", "was first demonstrated on", "first demonstrated on thrombospondin", "demonstrated on thrombospondin 1", "thrombospondin 1 found", "1 found in", "found in platelets and", "in platelets and the", "platelets and the ecm", "the ecm hofsteenge", "ecm hofsteenge et", "hofsteenge et al. 2001", "al. 2001 luo", "2001 luo et", "luo et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the resulting", ". the resulting o", "the resulting o fucosyl", "resulting o fucosyl protein", "o fucosyl protein is", "fucosyl protein is subsequently", "protein is subsequently a", "is subsequently a substrate", "subsequently a substrate for", "a substrate for beta", "substrate for beta 1", "for beta 1 3", "beta 1 3 glucosyltransferase", "1 3 glucosyltransferase like", "3 glucosyltransferase like protein", "like protein b3galtl", "b3galtl which", "which adds a glucosyl", "adds a glucosyl moiety", "a glucosyl moiety to", "glucosyl moiety to form", "moiety to form the", "to form the rare", "form the rare disaccharide", "the rare disaccharide modification", "rare disaccharide modification glc", "disaccharide modification glc beta", "modification glc beta 1", "glc beta 1 3", "beta 1 3 fuc.", "1 3 fuc. more", "3 fuc. more than", "fuc. more than 60", "more than 60 human", "than 60 human proteins", "60 human proteins contain", "human proteins contain tsr1", "proteins contain tsr1 domains", "tsr1 domains the", "domains the disaccharide", "the disaccharide modification has", "disaccharide modification has been", "modification has been demonstrated", "has been demonstrated on", "been demonstrated on a", "demonstrated on a small", "on a small number", "a small number of", "small number of these", "number of these tsr1", "of these tsr1 domain", "these tsr1 domain containing", "tsr1 domain containing proteins", "domain containing proteins such", "containing proteins such as", "proteins such as thrombospondin", "such as thrombospondin 1", "thrombospondin 1 hofsteenge", "1 hofsteenge et", "2006 properdin", "properdin gonzalez de", "gonzalez de peredo et", "de peredo et al.", "peredo et al. 2002", "al. 2002 and", "2002 and f", "f spondin gonzalez", "spondin gonzalez de", "et al. 2002 .", "al. 2002 . the", "2002 . the adamts", "the adamts a", "adamts a disintegrin", "a disintegrin like and", "disintegrin like and metalloprotease", "like and metalloprotease domain", "and metalloprotease domain with", "metalloprotease domain with thrombospondin", "domain with thrombospondin type", "with thrombospondin type 1", "thrombospondin type 1 repeats", "1 repeats superfamily", "repeats superfamily consists", "superfamily consists of 19", "consists of 19 secreted", "of 19 secreted metalloproteases", "secreted metalloproteases adamts", "metalloproteases adamts proteases", "adamts proteases and", "proteases and at", "and at lease five", "at lease five adamts", "lease five adamts like", "five adamts like proteins", "adamts like proteins in", "like proteins in humans.", "proteins in humans. five", "in humans. five members", "humans. five members of", "five members of the", "members of the adamts", "of the adamts superfamily", "the adamts superfamily have", "adamts superfamily have also", "superfamily have also had", "have also had experimental", "also had experimental confirmation", "had experimental confirmation of", "experimental confirmation of the", "confirmation of the disaccharide", "of the disaccharide modification.", "the disaccharide modification. examples", "disaccharide modification. examples are", "modification. examples are adamts13", "are adamts13 ricketts", "adamts13 ricketts et", "ricketts et al. 2007", "al. 2007 and", "2007 and adamtsl1", "and adamtsl1 wang", "adamtsl1 wang et", "wang et al. 2007", "et al. 2007 .", "al. 2007 . in", "2007 . in the", ". in the two", "in the two reactions", "the two reactions described", "two reactions described here", "described here the", "here the tsr1", "the tsr1 domain containing", "domain containing proteins with", "containing proteins with similarity", "proteins with similarity to", "with similarity to the", "similarity to the experimentally", "to the experimentally confirmed", "the experimentally confirmed ones", "experimentally confirmed ones are", "confirmed ones are included", "ones are included as", "are included as putative", "included as putative substrates.", "the o fucosylation of proteins", "o fucosylation of proteins containing", "fucosylation of proteins containing thrombospondin", "of proteins containing thrombospondin type", "proteins containing thrombospondin type 1", "containing thrombospondin type 1 repeat", "type 1 repeat tsr", "repeat tsr domains", "tsr domains is an", "domains is an important ptm", "an important ptm regulating", "important ptm regulating many", "ptm regulating many biological", "regulating many biological processes such", "many biological processes such as", "biological processes such as notch", "processes such as notch signalling", "as notch signalling inflammation", "signalling inflammation wound", "wound healing angiogenesis amd", "healing angiogenesis amd neoplasia", "angiogenesis amd neoplasia adams", "amd neoplasia adams &", "neoplasia adams & tucker", "& tucker 2000 moremen", "tucker 2000 moremen et", "2000 moremen et al.", "moremen et al. 2012 .", "et al. 2012 . fucose", "al. 2012 . fucose addition", "2012 . fucose addition is", ". fucose addition is carried", "fucose addition is carried out", "addition is carried out by", "is carried out by two", "carried out by two protein", "out by two protein fucosyltransferases", "two protein fucosyltransferases pofut1", "protein fucosyltransferases pofut1 and", "fucosyltransferases pofut1 and 2.", "pofut1 and 2. only pofut2", "and 2. only pofut2 recognises", "2. only pofut2 recognises the", "only pofut2 recognises the consensus", "pofut2 recognises the consensus sequence", "recognises the consensus sequence csxs/tcg", "the consensus sequence csxs/tcg found", "consensus sequence csxs/tcg found in", "sequence csxs/tcg found in tsr1", "csxs/tcg found in tsr1 domains", "found in tsr1 domains and", "in tsr1 domains and the", "tsr1 domains and the fucosyl", "domains and the fucosyl residue", "and the fucosyl residue is", "the fucosyl residue is attached", "fucosyl residue is attached to", "residue is attached to the", "is attached to the hydroxyl", "attached to the hydroxyl group", "to the hydroxyl group of", "the hydroxyl group of conserved", "hydroxyl group of conserved serine", "of conserved serine s", "serine s or", "threonine t residues", "t residues within the", "residues within the consensus sequence.", "within the consensus sequence. the", "the consensus sequence. the modification", "consensus sequence. the modification was", "sequence. the modification was first", "the modification was first demonstrated", "modification was first demonstrated on", "was first demonstrated on thrombospondin", "first demonstrated on thrombospondin 1", "on thrombospondin 1 found", "thrombospondin 1 found in", "1 found in platelets", "found in platelets and the", "in platelets and the ecm", "and the ecm hofsteenge", "the ecm hofsteenge et", "ecm hofsteenge et al.", "et al. 2001 luo", "al. 2001 luo et", "2001 luo et al.", "luo et al. 2006 .", "et al. 2006 . the", "al. 2006 . the resulting", "2006 . the resulting o", ". the resulting o fucosyl", "the resulting o fucosyl protein", "resulting o fucosyl protein is", "o fucosyl protein is subsequently", "fucosyl protein is subsequently a", "protein is subsequently a substrate", "is subsequently a substrate for", "subsequently a substrate for beta", "a substrate for beta 1", "substrate for beta 1 3", "for beta 1 3 glucosyltransferase", "beta 1 3 glucosyltransferase like", "1 3 glucosyltransferase like protein", "glucosyltransferase like protein b3galtl", "b3galtl which adds", "which adds a glucosyl moiety", "adds a glucosyl moiety to", "a glucosyl moiety to form", "glucosyl moiety to form the", "moiety to form the rare", "to form the rare disaccharide", "form the rare disaccharide modification", "the rare disaccharide modification glc", "rare disaccharide modification glc beta", "disaccharide modification glc beta 1", "modification glc beta 1 3", "glc beta 1 3 fuc.", "beta 1 3 fuc. more", "1 3 fuc. more than", "3 fuc. more than 60", "fuc. more than 60 human", "more than 60 human proteins", "than 60 human proteins contain", "60 human proteins contain tsr1", "human proteins contain tsr1 domains", "contain tsr1 domains the", "tsr1 domains the disaccharide", "domains the disaccharide modification", "the disaccharide modification has been", "disaccharide modification has been demonstrated", "modification has been demonstrated on", "has been demonstrated on a", "been demonstrated on a small", "demonstrated on a small number", "on a small number of", "a small number of these", "small number of these tsr1", "number of these tsr1 domain", "of these tsr1 domain containing", "these tsr1 domain containing proteins", "tsr1 domain containing proteins such", "domain containing proteins such as", "containing proteins such as thrombospondin", "proteins such as thrombospondin 1", "as thrombospondin 1 hofsteenge", "thrombospondin 1 hofsteenge et", "1 hofsteenge et al.", "al. 2006 properdin", "properdin gonzalez de peredo", "gonzalez de peredo et al.", "de peredo et al. 2002", "et al. 2002 and", "al. 2002 and f", "2002 and f spondin", "and f spondin gonzalez", "f spondin gonzalez de", "spondin gonzalez de peredo", "peredo et al. 2002 .", "et al. 2002 . the", "al. 2002 . the adamts", ". the adamts a", "the adamts a disintegrin", "adamts a disintegrin like", "a disintegrin like and metalloprotease", "disintegrin like and metalloprotease domain", "like and metalloprotease domain with", "and metalloprotease domain with thrombospondin", "metalloprotease domain with thrombospondin type", "domain with thrombospondin type 1", "with thrombospondin type 1 repeats", "type 1 repeats superfamily", "1 repeats superfamily consists", "repeats superfamily consists of", "superfamily consists of 19 secreted", "consists of 19 secreted metalloproteases", "19 secreted metalloproteases adamts", "secreted metalloproteases adamts proteases", "adamts proteases and at", "proteases and at lease", "and at lease five adamts", "at lease five adamts like", "lease five adamts like proteins", "five adamts like proteins in", "adamts like proteins in humans.", "like proteins in humans. five", "proteins in humans. five members", "in humans. five members of", "humans. five members of the", "five members of the adamts", "members of the adamts superfamily", "of the adamts superfamily have", "the adamts superfamily have also", "adamts superfamily have also had", "superfamily have also had experimental", "have also had experimental confirmation", "also had experimental confirmation of", "had experimental confirmation of the", "experimental confirmation of the disaccharide", "confirmation of the disaccharide modification.", "of the disaccharide modification. examples", "the disaccharide modification. examples are", "disaccharide modification. examples are adamts13", "examples are adamts13 ricketts", "are adamts13 ricketts et", "adamts13 ricketts et al.", "et al. 2007 and", "al. 2007 and adamtsl1", "and adamtsl1 wang et", "adamtsl1 wang et al.", "wang et al. 2007 .", "et al. 2007 . in", "al. 2007 . in the", "2007 . in the two", ". in the two reactions", "in the two reactions described", "the two reactions described here", "reactions described here the", "described here the tsr1", "here the tsr1 domain", "the tsr1 domain containing proteins", "tsr1 domain containing proteins with", "domain containing proteins with similarity", "containing proteins with similarity to", "proteins with similarity to the", "with similarity to the experimentally", "similarity to the experimentally confirmed", "to the experimentally confirmed 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"tightly regulated amounts in response", "regulated amounts in response to", "amounts in response to extracellular", "in response to extracellular signals.", "response to extracellular signals. both", "to extracellular signals. both lef", "extracellular signals. both lef and", "signals. both lef and cya", "both lef and cya depend", "lef and cya depend on", "and cya depend on paga", "cya depend on paga to", "depend on paga to enter", "on paga to enter their", "paga to enter their target", "to enter their target cells", "their target cells a", "target cells a strategy", "cells a strategy characteristic", "a strategy characteristic of bacterial", "strategy characteristic of bacterial binary", "characteristic of bacterial binary toxins", "bacterial binary toxins barth", "binary toxins barth et", "toxins barth et al.", "barth et al. 2004 .", "et al. 2004 . paga", "al. 2004 . paga binds", "2004 . paga binds to", ". paga binds to the", "paga binds to the target", "binds to the target cell", "to the target cell receptors", "target cell receptors is", "cell receptors is cleaved", "receptors is cleaved by", "is cleaved by furin or", "cleaved by furin or other", "by furin or other cellular", "furin or other cellular proteases", "other cellular proteases and", "cellular proteases and thereupon", "proteases and thereupon forms", "and thereupon forms an oligomer", "thereupon forms an oligomer that", "forms an oligomer that exposes", "an oligomer that exposes binding", "oligomer that exposes binding sites", "that exposes binding sites for", "exposes binding sites for lef", "binding sites for lef and", "sites for lef and cya", "for lef and cya molecules", "and cya molecules young", "cya molecules young and", "molecules young and collier", "and collier 2007 . this", "collier 2007 . this complex", "2007 . this complex is", ". this complex is taken", "this complex is taken into", "complex is taken into the", "is taken into the target", "taken into the target cell", "into the target cell by", "the target cell by clathrin", "target cell by clathrin mediated", "cell by clathrin mediated endocytosis", "by clathrin mediated endocytosis and", "clathrin mediated endocytosis and delivered", "mediated endocytosis and delivered to", "endocytosis and delivered to endosomes.", "and delivered to endosomes. the", "delivered to endosomes. the low", "to endosomes. the low ph", "endosomes. the low ph of", "the low ph of the", "low ph of the endosome", "ph of the endosome causes", "of the endosome causes the", "the endosome causes the bacterial", "endosome causes the bacterial toxin", "causes the bacterial toxin complex", "the bacterial toxin complex to", "bacterial toxin complex to rearrange:", "toxin complex to rearrange: the", "complex to rearrange: the paga", "to rearrange: the paga oligomer", "rearrange: the paga oligomer forms", "the paga oligomer forms a", "paga oligomer forms a pore", "oligomer forms a pore in", "forms a pore in the", "a pore in the endosome", "pore in the endosome membrane", "in the endosome membrane through", "the endosome membrane through which", "endosome membrane through which lef", "membrane through which lef and", "through which lef and cya", "which lef and cya molecules", "lef and cya molecules enter", "and cya molecules enter the", "cya molecules enter the target", "molecules enter the target cell", "enter the target cell cytosol." ] }, { "record_id": "GLY_000594_1_410", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5213460", "r hsa", "hsa 5213460", "r hsa 5213460" ] }, { "record_id": "GLY_000594_1_410", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ripk1 mediated", "mediated regulated", "regulated necrosis", "ripk1 mediated regulated", "mediated regulated necrosis", "ripk1 mediated regulated necrosis", "receptor interacting", "interacting serine/threonine", "serine/threonine kinase", "kinase protein", "protein 1", "and ripk3", "ripk3 dependent", "dependent necrosis", "necrosis is", "is called", "called necroptosis", "necroptosis or", "or programmed", "programmed necrosis.", "necrosis. the", "the kinase", "kinase activities", "activities of", "of ripk1", "ripk1 and", "ripk3 are", "are essential", "essential for", "for the", "the necroptotic", "necroptotic cell", "cell death", "death in", "in human", "mouse cell", "cell lines", "lines and", "and genetic", "genetic mice", "mice models", "cho ys", "ys et", "et al.", "al. 2009", "he s", "s et", "zhang dw", "dw et", "mcquade t", "t et", "al. 2013", "newton et", "al. 2014", "2014 .", ". the", "the initiation", "initiation of", "of necroptosis", "necroptosis can", "can be", "be stimulated", "stimulated by", "by the", "the same", "same death", "death ligands", "ligands that", "that activate", "activate extrinsic", "extrinsic apoptotic", "apoptotic signaling", "signaling pathway", "such as", "as tumor", "tumor necrosis", "necrosis factor", "fas ligand", "and trail", "tnf related", "related apoptosis", "apoptosis inducing", "inducing ligand", "or toll", "toll like", "like receptors", "receptors 3", "3 and", "and 4", "4 ligands", "holler n", "n et", "al. 2000", "feoktistova m", "m et", "al. 2011", "voigt s", ". in", "in contrast", "contrast to", "to apoptosis", "necroptosis represents", "represents a", "a form", "form of", "of cell", "death that", "that is", "is optimally", "optimally induced", "induced when", "when caspases", "caspases are", "are inhibited", "hopkins donaldson", "donaldson s", "sawai h", "h 2014", ". specific", "specific inhibitors", "inhibitors of", "of caspase", "caspase independent", "independent necrosis", "have recently", "recently been", "been identified", "degterev a", "a et", "al. 2005", "2008 .", ". necrostatins", "necrostatins have", "have been", "been shown", "shown to", "to inhibit", "inhibit the", "kinase activity", "activity of", "al. 2008", ". importantly", "death of", "of apoptotic", "apoptotic morphology", "morphology can", "be shifted", "shifted to", "to a", "a necrotic", "necrotic phenotype", "phenotype when", "when caspase", "caspase 8", "8 activity", "activity is", "is compromised", "otherwise active", "active caspase", "8 blocks", "blocks necroptosis", "necroptosis by", "the proteolytic", "proteolytic cleavage", "cleavage of", "kalai m", "al. 2002", "lin y", "y et", "al. 1999", "feng s", "al. 2007", "2007 .", ". when", "caspase activity", "is inhibited", "inhibited under", "under certain", "certain pathophysiological", "pathophysiological conditions", "conditions or", "or by", "by pharmacological", "pharmacological agents", "deubiquitinated ripk1", "ripk1 is", "is engaged", "engaged in", "in physical", "physical and", "and functional", "functional interactions", "interactions with", "with the", "the cognate", "cognate kinase", "kinase ripk3", "ripk3 leading", "leading to", "to formation", "formation of", "of necrosome", "a necroptosis", "necroptosis inducing", "inducing complex", "complex consisting", "consisting of", "h 2013", "moquin dm", "dm et", "2009 .", ". within", "within the", "the necrosome", "necrosome ripk1", "ripk3 bind", "bind to", "to each", "each other", "other through", "through their", "their rip", "rip homotypic", "homotypic interaction", "interaction motif", "domains. the", "the rhims", "rhims can", "can facilitate", "facilitate ripk1:ripk3", "ripk1:ripk3 oligomerization", "allowing them", "them to", "to form", "form amyloid", "amyloid like", "like fibrillar", "fibrillar structures", "li j", "j et", "al. 2012", "mompean m", "al. 2018", "2018 .", ". ripk3", "ripk3 in", "in turn", "turn interacts", "interacts with", "with mixed", "mixed lineage", "lineage kinase", "kinase domain", "domain like", "like protein", "sun l", "l et", "zhao j", "murphy jm", "jm et", "chen w", "w et", "2013 .", "the precise", "precise mechanism", "mechanism of", "of mlkl", "mlkl activation", "activation by", "by ripk3", "ripk3 is", "is incompletely", "incompletely understood", "understood and", "and may", "may vary", "vary across", "across species", "davies ka", "ka et", "al. 2020", "2020 .", ". mouse", "mouse mlkl", "activation relies", "relies on", "on transient", "transient engagement", "engagement of", "of ripk3", "ripk3 to", "to facilitate", "facilitate phosphorylation", "phosphorylation of", "of the", "the pseudokinase", "pseudokinase domain", "petrie ej", "ej et", "al. 2019a", "while it", "it appears", "appears that", "that stable", "stable recruitment", "recruitment of", "of human", "human mlkl", "mlkl by", "by necrosomal", "necrosomal ripk3", "is an", "an additional", "additional crucial", "crucial step", "step in", "2019b .", "ripk3 mediated", "mediated phosphorylation", "phosphorylation is", "is thought", "thought to", "to initiate", "initiate mlkl", "mlkl oligomerization", "membrane translocation", "translocation and", "and membrane", "membrane disruption", "wang h", "h et", "samson al", "al et", ". studies", "studies in", "human cell", "lines suggest", "suggest that", "that upon", "upon induction", "induction of", "necroptosis mlkl", "mlkl shifts", "shifts to", "to the", "the plasma", "plasma membrane", "membrane and", "and membranous", "membranous organelles", "organelles such", "as mitochondria", "endosome and", "and er", "but it", "it is", "is trafficking", "trafficking via", "via a", "a golgi", "golgi microtubule", "microtubule actin", "actin dependent", "dependent mechanism", "mechanism that", "that facilitates", "facilitates plasma", "where membrane", "disruption causes", "causes death", "the mechanisms", "mechanisms of", "necroptosis regulation", "regulation and", "and execution", "execution downstream", "downstream of", "mlkl remain", "remain elusive.", "elusive. the", "precise oligomeric", "oligomeric form", "mlkl that", "that mediates", "mediates plasma", "disruption has", "has been", "been highly", "highly debated", "cai z", "z et", "chen x", "x et", "dondelinger y", "al. 2017", ". however", "microscopy data", "data revealed", "revealed that", "that mlkl", "mlkl assembles", "assembles into", "into higher", "higher molecular", "molecular weight", "weight species", "species upon", "upon cytoplasmic", "cytoplasmic necrosomes", "necrosomes within", "within human", "human cells", "and upon", "upon phosphorylation", "phosphorylation by", "mlkl is", "is trafficked", "trafficked to", ". at", "at the", "phospho mlkl", "mlkl forms", "forms heterogeneous", "heterogeneous higher", "higher order", "order assemblies", "which are", "are thought", "to permeabilize", "permeabilize cells", "to release", "release of", "of damps", "damps to", "to invoke", "invoke inflammatory", "inflammatory responses.", "responses. mlkl", "mlkl also", "also exerts", "exerts non", "non necroptotic", "necroptotic functions", "functions such", "as regulation", "regulation of", "of endosomal", "endosomal trafficking", "trafficking or", "or mlkl", "mlkl induced", "induced activation", "activation of", "the nlrp3", "nlrp3 inflammasome", "yoon s", "shlomovitz i", "i et", "al. 2022", "2022 .", ". while", "while ripk1", "ripk3 and", "and mlkl", "mlkl are", "are the", "the core", "core signaling", "signaling components", "components in", "in the", "the necroptosis", "necroptosis pathway", "many additional", "additional molecules", "molecules have", "been proposed", "proposed to", "to positively", "positively and", "and negatively", "negatively tune", "tune the", "the signaling", "signaling pathway.", "pathway. currently", "this picture", "picture is", "is evolving", "evolving rapidly", "rapidly as", "as new", "new modulators", "modulators continue", "continue to", "to be", "be discovered.

the", "discovered.

the reactome", "reactome module", "module describes", "describes mlkl", "mlkl mediated", "mediated necroptotic", "necroptotic events", "events on", "on the", "plasma membrane.", "receptor interacting serine/threonine", "interacting serine/threonine kinase", "serine/threonine kinase protein", "kinase protein 1", "1 ripk1", "and ripk3 dependent", "ripk3 dependent necrosis", "dependent necrosis is", "necrosis is called", "is called necroptosis", "called necroptosis or", "necroptosis or programmed", "or programmed necrosis.", "programmed necrosis. the", "necrosis. the kinase", "the kinase activities", "kinase activities of", "activities of ripk1", "of ripk1 and", "ripk1 and ripk3", "and ripk3 are", "ripk3 are essential", "are essential for", "essential for the", "for the necroptotic", "the necroptotic cell", "necroptotic cell death", "cell death in", "death in human", "human mouse", "mouse cell lines", "cell lines and", "lines and genetic", "and genetic mice", "genetic mice models", "models cho", "cho ys et", "ys et al.", "et al. 2009", "2009 he", "he s et", "s et al.", "2009 2011", "2011 zhang", "zhang dw et", "dw et al.", "2009 mcquade", "mcquade t et", "t et al.", "et al. 2013", "2013 newton", "newton et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the initiation", "the initiation of", "initiation of necroptosis", "of necroptosis can", "necroptosis can be", "can be stimulated", "be stimulated by", "stimulated by the", "by the same", "the same death", "same death ligands", "death ligands that", "ligands that activate", "that activate extrinsic", "activate extrinsic apoptotic", "extrinsic apoptotic signaling", "apoptotic signaling pathway", "pathway such", "such as tumor", "as tumor necrosis", "tumor necrosis factor", "factor tnf", "tnf alpha", "alpha fas", "ligand fasl", "trail tnf", "tnf related apoptosis", "related apoptosis inducing", "apoptosis inducing ligand", "ligand or", "or toll like", "toll like receptors", "like receptors 3", "receptors 3 and", "3 and 4", "and 4 ligands", "ligands holler", "holler n et", "n et al.", "et al. 2000", "2000 he", "2009 feoktistova", "feoktistova m et", "m et al.", "et al. 2011", "2011 voigt", "voigt s et", "2014 . in", ". in contrast", "in contrast to", "contrast to apoptosis", "apoptosis necroptosis", "necroptosis represents a", "represents a form", "a form of", "form of cell", "of cell death", "cell death that", "death that is", "that is optimally", "is optimally induced", "optimally induced when", "induced when caspases", "when caspases are", "caspases are inhibited", "inhibited holler", "2000 hopkins", "hopkins donaldson s", "donaldson s et", "2000 sawai", "sawai h 2014", "h 2014 .", "2014 . specific", ". specific inhibitors", "specific inhibitors of", "inhibitors of caspase", "of caspase independent", "caspase independent necrosis", "necrosis necrostatins", "have recently been", "recently been identified", "identified degterev", "degterev a et", "a et al.", "et al. 2005", "2005 2008", "2008 . necrostatins", ". necrostatins have", "necrostatins have been", "have been shown", "been shown to", "shown to inhibit", "to inhibit the", "inhibit the kinase", "the kinase activity", "kinase activity of", "activity of ripk1", "ripk1 degterev", "et al. 2008", "al. 2008 .", "2008 . importantly", "importantly cell", "cell death of", "death of apoptotic", "of apoptotic morphology", "apoptotic morphology can", "morphology can be", "can be shifted", "be shifted to", "shifted to a", "to a necrotic", "a necrotic phenotype", "necrotic phenotype when", "phenotype when caspase", "when caspase 8", "caspase 8 activity", "8 activity is", "activity is compromised", "compromised otherwise", "otherwise active caspase", "active caspase 8", "caspase 8 blocks", "8 blocks necroptosis", "blocks necroptosis by", "necroptosis by the", "by the proteolytic", "the proteolytic cleavage", "proteolytic cleavage of", "cleavage of ripk1", "ripk3 kalai", "kalai m et", "et al. 2002", "2002 degterev", "2008 lin", "lin y et", "y et al.", "et al. 1999", "1999 feng", "feng s et", "et al. 2007", "al. 2007 .", "2007 . when", ". when caspase", "when caspase activity", "caspase activity is", "activity is inhibited", "is inhibited under", "inhibited under certain", "under certain pathophysiological", "certain pathophysiological conditions", "pathophysiological conditions or", "conditions or by", "or by pharmacological", "by pharmacological agents", "agents deubiquitinated", "deubiquitinated ripk1 is", "ripk1 is engaged", "is engaged in", "engaged in physical", "in physical and", "physical and functional", "and functional interactions", "functional interactions with", "interactions with the", "with the cognate", "the cognate kinase", "cognate kinase ripk3", "kinase ripk3 leading", "ripk3 leading to", "leading to formation", "to formation of", "formation of necrosome", "necrosome a", "a necroptosis inducing", "necroptosis inducing complex", "inducing complex consisting", "complex consisting of", "consisting of ripk1", "ripk3 sawai", "sawai h 2013", "2013 moquin", "moquin dm et", "dm et al.", "2013 kalai", "2002 cho", "2009 zhang", "al. 2009 .", "2009 . within", ". within the", "within the necrosome", "the necrosome ripk1", "necrosome ripk1 and", "and ripk3 bind", "ripk3 bind to", "bind to each", "to each other", "each other through", "other through their", "through their rip", "their rip homotypic", "rip homotypic interaction", "homotypic interaction motif", "motif rhim", "rhim domains.", "domains. the rhims", "the rhims can", "rhims can facilitate", "can facilitate ripk1:ripk3", "facilitate ripk1:ripk3 oligomerization", "oligomerization allowing", "allowing them to", "them to form", "to form amyloid", "form amyloid like", "amyloid like fibrillar", "like fibrillar structures", "structures li", "li j et", "j et al.", "et al. 2012", "2012 mompean", "mompean m et", "et al. 2018", "al. 2018 .", "2018 . ripk3", ". ripk3 in", "ripk3 in turn", "in turn interacts", "turn interacts with", "interacts with mixed", "with mixed lineage", "mixed lineage kinase", "lineage kinase domain", "kinase domain like", "domain like protein", "protein mlkl", "sun l et", "l et al.", "2012 zhao", "zhao j et", "2012 murphy", "murphy jm et", "jm et al.", "2013 chen", "chen w et", "w et al.", "al. 2013 .", "2013 . the", ". the precise", "the precise mechanism", "precise mechanism of", "mechanism of mlkl", "of mlkl activation", "mlkl activation by", "activation by ripk3", "by ripk3 is", "ripk3 is incompletely", "is incompletely understood", "incompletely understood and", "understood and may", "and may vary", "may vary across", "vary across species", "species davies", "davies ka et", "ka et al.", "et al. 2020", "al. 2020 .", "2020 . mouse", ". mouse mlkl", "mouse mlkl activation", "mlkl activation relies", "activation relies on", "relies on transient", "on transient engagement", "transient engagement of", "engagement of ripk3", "of ripk3 to", "ripk3 to facilitate", "to facilitate phosphorylation", "facilitate phosphorylation of", "phosphorylation of the", "of the pseudokinase", "the pseudokinase domain", "domain murphy", "2013 petrie", "petrie ej et", "ej et al.", "et al. 2019a", "while it appears", "it appears that", "appears that stable", "that stable recruitment", "stable recruitment of", "recruitment of human", "of human mlkl", "human mlkl by", "mlkl by necrosomal", "by necrosomal ripk3", "necrosomal ripk3 is", "ripk3 is an", "is an additional", "an additional crucial", "additional crucial step", "crucial step in", "step in human", "in human mlkl", "human mlkl activation", "activation davies", "2018 petrie", "2018 2019b", "2019b . ripk3", ". ripk3 mediated", "ripk3 mediated phosphorylation", "mediated phosphorylation is", "phosphorylation is thought", "is thought to", "thought to initiate", "to initiate mlkl", "initiate mlkl oligomerization", "oligomerization membrane", "membrane translocation and", "translocation and membrane", "and membrane disruption", "disruption sun", "2012 wang", "wang h et", "h et al.", "2014 petrie", "2020 samson", "samson al et", "al et al.", "2020 . studies", ". studies in", "studies in human", "in human cell", "human cell lines", "cell lines suggest", "lines suggest that", "suggest that upon", "that upon induction", "upon induction of", "induction of necroptosis", "of necroptosis mlkl", "necroptosis mlkl shifts", "mlkl shifts to", "shifts to the", "to the plasma", "the plasma membrane", "plasma membrane and", "membrane and membranous", "and membranous organelles", "membranous organelles such", "organelles such as", "such as mitochondria", "mitochondria lysosome", "lysosome endosome", "endosome and er", "er wang", "but it is", "it is trafficking", "is trafficking via", "trafficking via a", "via a golgi", "a golgi microtubule", "golgi microtubule actin", "microtubule actin dependent", "actin dependent mechanism", "dependent mechanism that", "mechanism that facilitates", "that facilitates plasma", "facilitates plasma membrane", "plasma membrane translocation", "translocation where", "where membrane disruption", "membrane disruption causes", "disruption causes death", "death samson", "2020 . the", ". the mechanisms", "the mechanisms of", "mechanisms of necroptosis", "of necroptosis regulation", "necroptosis regulation and", "regulation and execution", "and execution downstream", "execution downstream of", "downstream of mlkl", "of mlkl remain", "mlkl remain elusive.", "remain elusive. the", "elusive. the precise", "the precise oligomeric", "precise oligomeric form", "oligomeric form of", "form of mlkl", "of mlkl that", "mlkl that mediates", "that mediates plasma", "mediates plasma membrane", "plasma membrane disruption", "membrane disruption has", "disruption has been", "has been highly", "been highly debated", "debated cai", "cai z et", "z et al.", "2014 chen", "chen x et", "x et al.", "2014 dondelinger", "dondelinger y et", "2014 wang", "et al. 2017", "2017 2018", "2018 samson", "however microscopy", "microscopy data revealed", "data revealed that", "revealed that mlkl", "that mlkl assembles", "mlkl assembles into", "assembles into higher", "into higher molecular", "higher molecular weight", "molecular weight species", "weight species upon", "species upon cytoplasmic", "upon cytoplasmic necrosomes", "cytoplasmic necrosomes within", "necrosomes within human", "within human cells", "cells and", "and upon phosphorylation", "upon phosphorylation by", "phosphorylation by ripk3", "ripk3 mlkl", "mlkl is trafficked", "is trafficked to", "trafficked to the", "membrane samson", "2020 . at", ". at the", "at the plasma", "membrane phospho", "phospho mlkl forms", "mlkl forms heterogeneous", "forms heterogeneous higher", "heterogeneous higher order", "higher order assemblies", "assemblies which", "which are thought", "are thought to", "thought to permeabilize", "to permeabilize cells", "cells leading", "leading to release", "to release of", "release of damps", "of damps to", "damps to invoke", "to invoke inflammatory", "invoke inflammatory responses.", "inflammatory responses. mlkl", "responses. mlkl also", "mlkl also exerts", "also exerts non", "exerts non necroptotic", "non necroptotic functions", "necroptotic functions such", "functions such as", "such as regulation", "as regulation of", "regulation of endosomal", "of endosomal trafficking", "endosomal trafficking or", "trafficking or mlkl", "or mlkl induced", "mlkl induced activation", "induced activation of", "activation of the", "of the nlrp3", "the nlrp3 inflammasome", "inflammasome yoon", "yoon s et", "2017 shlomovitz", "shlomovitz i et", "i et al.", "2020 yoon", "et al. 2022", "al. 2022 .", "2022 . while", ". while ripk1", "ripk1 ripk3", "ripk3 and mlkl", "and mlkl are", "mlkl are the", "are the core", "the core signaling", "core signaling components", "signaling components in", "components in the", "in the necroptosis", "the necroptosis pathway", "pathway many", "many additional molecules", "additional molecules have", "molecules have been", "have been proposed", "been proposed to", "proposed to positively", "to positively and", "positively and negatively", "and negatively tune", "negatively tune the", "tune the signaling", "the signaling pathway.", "signaling pathway. currently", "currently this", "this picture is", "picture is evolving", "is evolving rapidly", "evolving rapidly as", "rapidly as new", "as new modulators", "new modulators continue", "modulators continue to", "continue to be", "to be discovered.

the", "be discovered.

the reactome", "discovered.

the reactome module", "reactome module describes", "module describes mlkl", "describes mlkl mediated", "mlkl mediated necroptotic", "mediated necroptotic events", "necroptotic events on", "events on the", "on the plasma", "the plasma membrane.", "receptor interacting serine/threonine kinase", "interacting serine/threonine kinase protein", "serine/threonine kinase protein 1", "protein 1 ripk1", "and ripk3 dependent necrosis", "ripk3 dependent necrosis is", "dependent necrosis is called", "necrosis is called necroptosis", "is called necroptosis or", "called necroptosis or programmed", "necroptosis or programmed necrosis.", "or programmed necrosis. the", "programmed necrosis. the kinase", "necrosis. the kinase activities", "the kinase activities of", "kinase activities of ripk1", "activities of ripk1 and", "of ripk1 and ripk3", "ripk1 and ripk3 are", "and ripk3 are essential", "ripk3 are essential for", "are essential for the", "essential for the necroptotic", "for the necroptotic cell", "the necroptotic cell death", "necroptotic cell death in", "cell death in human", "in human mouse", "human mouse cell", "mouse cell lines and", "cell lines and genetic", "lines and genetic mice", "and genetic mice models", "mice models cho", "models cho ys", "cho ys et al.", "ys et al. 2009", "al. 2009 he", "2009 he s", "he s et al.", "s et al. 2009", "al. 2009 2011", "2011 zhang dw", "zhang dw et al.", "dw et al. 2009", "al. 2009 mcquade", "2009 mcquade t", "mcquade t et al.", "t et al. 2013", "al. 2013 newton", "2013 newton et", "newton et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the initiation", ". the initiation of", "the initiation of necroptosis", "initiation of necroptosis can", "of necroptosis can be", "necroptosis can be stimulated", "can be stimulated by", "be stimulated by the", "stimulated by the same", "by the same death", "the same death ligands", "same death ligands that", "death ligands that activate", "ligands that activate extrinsic", "that activate extrinsic apoptotic", "activate extrinsic apoptotic signaling", "extrinsic apoptotic signaling pathway", "signaling pathway such", "pathway such as", "such as tumor necrosis", "as tumor necrosis factor", "necrosis factor tnf", "alpha fas ligand", "fas ligand fasl", "fasl and", "and trail tnf", "trail tnf related", "tnf related apoptosis inducing", "related apoptosis inducing ligand", "inducing ligand or", "ligand or toll", "or toll like receptors", "toll like receptors 3", "like receptors 3 and", "receptors 3 and 4", "3 and 4 ligands", "4 ligands holler", "ligands holler n", "holler n et al.", "n et al. 2000", "al. 2000 he", "2000 he s", "al. 2009 feoktistova", "2009 feoktistova m", "feoktistova m et al.", "m et al. 2011", "al. 2011 voigt", "2011 voigt s", "voigt s et al.", "s et al. 2014", "al. 2014 . in", "2014 . in contrast", ". in contrast to", "in contrast to apoptosis", "to apoptosis necroptosis", "apoptosis necroptosis represents", "necroptosis represents a form", "represents a form of", "a form of cell", "form of cell death", "of cell death that", "cell death that is", "death that is optimally", "that is optimally induced", "is optimally induced when", "optimally induced when caspases", "induced when caspases are", "when caspases are inhibited", "are inhibited holler", "inhibited holler n", "al. 2000 hopkins", "2000 hopkins donaldson", "hopkins donaldson s et", "donaldson s et al.", "s et al. 2000", "al. 2000 sawai", "2000 sawai h", "sawai h 2014 .", "h 2014 . specific", "2014 . specific inhibitors", ". specific inhibitors of", "specific inhibitors of caspase", "inhibitors of caspase independent", "of caspase independent necrosis", "independent necrosis necrostatins", "necrostatins have recently", "have recently been identified", "been identified degterev", "identified degterev a", "degterev a et al.", "a et al. 2005", "al. 2005 2008", "2005 2008 .", "2008 . necrostatins have", ". necrostatins have been", "necrostatins have been shown", "have been shown to", "been shown to inhibit", "shown to inhibit the", "to inhibit the kinase", "inhibit the kinase activity", "the kinase activity of", "kinase activity of ripk1", "of ripk1 degterev", "ripk1 degterev a", "a et al. 2008", "et al. 2008 .", "al. 2008 . importantly", ". importantly cell", "importantly cell death", "cell death of apoptotic", "death of apoptotic morphology", "of apoptotic morphology can", "apoptotic morphology can be", "morphology can be shifted", "can be shifted to", "be shifted to a", "shifted to a necrotic", "to a necrotic phenotype", "a necrotic phenotype when", "necrotic phenotype when caspase", "phenotype when caspase 8", "when caspase 8 activity", "caspase 8 activity is", "8 activity is compromised", "is compromised otherwise", "compromised otherwise active", "otherwise active caspase 8", "active caspase 8 blocks", "caspase 8 blocks necroptosis", "8 blocks necroptosis by", "blocks necroptosis by the", "necroptosis by the proteolytic", "by the proteolytic cleavage", "the proteolytic cleavage of", "proteolytic cleavage of ripk1", "cleavage of ripk1 and", "and ripk3 kalai", "ripk3 kalai m", "kalai m et al.", "m et al. 2002", "al. 2002 degterev", "2002 degterev a", "al. 2008 lin", "2008 lin y", "lin y et al.", "y et al. 1999", "al. 1999 feng", "1999 feng s", "feng s et al.", "s et al. 2007", "et al. 2007 .", "al. 2007 . when", "2007 . when caspase", ". when caspase activity", "when caspase activity is", "caspase activity is inhibited", "activity is inhibited under", "is inhibited under certain", "inhibited under certain pathophysiological", "under certain pathophysiological conditions", "certain pathophysiological conditions or", "pathophysiological conditions or by", "conditions or by pharmacological", "or by pharmacological agents", "pharmacological agents deubiquitinated", "agents deubiquitinated ripk1", "deubiquitinated ripk1 is engaged", "ripk1 is engaged in", "is engaged in physical", "engaged in physical and", "in physical and functional", "physical and functional interactions", "and functional interactions with", "functional interactions with the", "interactions with the cognate", "with the cognate kinase", "the cognate kinase ripk3", "cognate kinase ripk3 leading", "kinase ripk3 leading to", "ripk3 leading to formation", "leading to formation of", "to formation of necrosome", "of necrosome a", "necrosome a necroptosis", "a necroptosis inducing complex", "necroptosis inducing complex consisting", "inducing complex consisting of", "complex consisting of ripk1", "consisting of ripk1 and", "and ripk3 sawai", "ripk3 sawai h", "h 2013 moquin", "2013 moquin dm", "moquin dm et al.", "dm et al. 2013", "al. 2013 kalai", "2013 kalai m", "al. 2002 cho", "2002 cho ys", "al. 2009 zhang", "2009 zhang dw", "et al. 2009 .", "al. 2009 . within", "2009 . within the", ". within the necrosome", "within the necrosome ripk1", "the necrosome ripk1 and", "necrosome ripk1 and ripk3", "ripk1 and ripk3 bind", "and ripk3 bind to", "ripk3 bind to each", "bind to each other", "to each other through", "each other through their", "other through their rip", "through their rip homotypic", "their rip homotypic interaction", "rip homotypic interaction motif", "interaction motif rhim", "rhim domains. the", "domains. the rhims can", "the rhims can facilitate", "rhims can facilitate ripk1:ripk3", "can facilitate ripk1:ripk3 oligomerization", "ripk1:ripk3 oligomerization allowing", "oligomerization allowing them", "allowing them to form", "them to form amyloid", "to form amyloid like", "form amyloid like fibrillar", "amyloid like fibrillar structures", "fibrillar structures li", "structures li j", "li j et al.", "j et al. 2012", "al. 2012 mompean", "2012 mompean m", "mompean m et al.", "m et al. 2018", "et al. 2018 .", "al. 2018 . ripk3", "2018 . ripk3 in", ". ripk3 in turn", "ripk3 in turn interacts", "in turn interacts with", "turn interacts with mixed", "interacts with mixed lineage", "with mixed lineage kinase", "mixed lineage kinase domain", "lineage kinase domain like", "kinase domain like protein", "like protein mlkl", "mlkl sun", "sun l et al.", "l et al. 2012", "al. 2012 zhao", "2012 zhao j", "zhao j et al.", "al. 2012 murphy", "2012 murphy jm", "murphy jm et al.", "jm et al. 2013", "al. 2013 chen", "2013 chen w", "chen w et al.", "w et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the precise", ". the precise mechanism", "the precise mechanism of", "precise mechanism of mlkl", "mechanism of mlkl activation", "of mlkl activation by", "mlkl activation by ripk3", "activation by ripk3 is", "by ripk3 is incompletely", "ripk3 is incompletely understood", "is incompletely understood and", "incompletely understood and may", "understood and may vary", "and may vary across", "may vary across species", "across species davies", "species davies ka", "davies ka et al.", "ka et al. 2020", "et al. 2020 .", "al. 2020 . mouse", "2020 . mouse mlkl", ". mouse mlkl activation", "mouse mlkl activation relies", "mlkl activation relies on", "activation relies on transient", "relies on transient engagement", "on transient engagement of", "transient engagement of ripk3", "engagement of ripk3 to", "of ripk3 to facilitate", "ripk3 to facilitate phosphorylation", "to facilitate phosphorylation of", "facilitate phosphorylation of the", "phosphorylation of the pseudokinase", "of the pseudokinase domain", "pseudokinase domain murphy", "domain murphy jm", "al. 2013 petrie", "2013 petrie ej", "petrie ej et al.", "ej et al. 2019a", "2019a while", "while it appears that", "it appears that stable", "appears that stable recruitment", "that stable recruitment of", "stable recruitment of human", "recruitment of human mlkl", "of human mlkl by", "human mlkl by necrosomal", "mlkl by necrosomal ripk3", "by necrosomal ripk3 is", "necrosomal ripk3 is an", "ripk3 is an additional", "is an additional crucial", "an additional crucial step", "additional crucial step in", "crucial step in human", "step in human mlkl", "in human mlkl activation", "mlkl activation davies", "activation davies ka", "ka et al. 2018", "al. 2018 petrie", "2018 petrie ej", "ej et al. 2018", "al. 2018 2019b", "2018 2019b .", "2019b . ripk3 mediated", ". ripk3 mediated phosphorylation", "ripk3 mediated phosphorylation is", "mediated phosphorylation is thought", "phosphorylation is thought to", "is thought to initiate", "thought to initiate mlkl", "to initiate mlkl oligomerization", "mlkl oligomerization membrane", "oligomerization membrane translocation", "membrane translocation and membrane", "translocation and membrane disruption", "membrane disruption sun", "disruption sun l", "al. 2012 wang", "2012 wang h", "wang h et al.", "h et al. 2014", "al. 2014 petrie", "2014 petrie ej", "ej et al. 2020", "al. 2020 samson", "2020 samson al", "samson al et al.", "al et al. 2020", "al. 2020 . studies", "2020 . studies in", ". studies in human", "studies in human cell", "in human cell lines", "human cell lines suggest", "cell lines suggest that", "lines suggest that upon", "suggest that upon induction", "that upon induction of", "upon induction of necroptosis", "induction of necroptosis mlkl", "of necroptosis mlkl shifts", "necroptosis mlkl shifts to", "mlkl shifts to the", "shifts to the plasma", "to the plasma membrane", "the plasma membrane and", "plasma membrane and membranous", "membrane and membranous organelles", "and membranous organelles such", "membranous organelles such as", "organelles such as mitochondria", "as mitochondria lysosome", "lysosome endosome and", "and er wang", "er wang h", "2014 but", "but it is trafficking", "it is trafficking via", "is trafficking via a", "trafficking via a golgi", "via a golgi microtubule", "a golgi microtubule actin", "golgi microtubule actin dependent", "microtubule actin dependent mechanism", "actin dependent mechanism that", "dependent mechanism that facilitates", "mechanism that facilitates plasma", "that facilitates plasma membrane", "facilitates plasma membrane translocation", "membrane translocation where", "translocation where membrane", "where membrane disruption causes", "membrane disruption causes death", "causes death samson", "death samson al", "al. 2020 . the", "2020 . the mechanisms", ". the mechanisms of", "the mechanisms of necroptosis", "mechanisms of necroptosis regulation", "of necroptosis regulation and", "necroptosis regulation and execution", "regulation and execution downstream", "and execution downstream of", "execution downstream of mlkl", "downstream of mlkl remain", "of mlkl remain elusive.", "mlkl remain elusive. the", "remain elusive. the precise", "elusive. the precise oligomeric", "the precise oligomeric form", "precise oligomeric form of", "oligomeric form of mlkl", "form of mlkl that", "of mlkl that mediates", "mlkl that mediates plasma", "that mediates plasma membrane", "mediates plasma membrane disruption", "plasma membrane disruption has", "membrane disruption has been", "disruption has been highly", "has been highly debated", "highly debated cai", "debated cai z", "cai z et al.", "z et al. 2014", "al. 2014 chen", "2014 chen x", "chen x et al.", "x et al. 2014", "al. 2014 dondelinger", "2014 dondelinger y", "dondelinger y et al.", "y et al. 2014", "al. 2014 wang", "2014 wang h", "ej et al. 2017", "al. 2017 2018", "2018 samson al", "2020 . however", ". however microscopy", "however microscopy data", "microscopy data revealed that", "data revealed that mlkl", "revealed that mlkl assembles", "that mlkl assembles into", "mlkl assembles into higher", "assembles into higher molecular", "into higher molecular weight", "higher molecular weight species", "molecular weight species upon", "weight species upon cytoplasmic", "species upon cytoplasmic necrosomes", "upon cytoplasmic necrosomes within", "cytoplasmic necrosomes within human", "necrosomes within human cells", "human cells and", "cells and upon", "and upon phosphorylation by", "upon phosphorylation by ripk3", "by ripk3 mlkl", "ripk3 mlkl is", "mlkl is trafficked to", "is trafficked to the", "trafficked to the plasma", "plasma membrane samson", "membrane samson al", "al. 2020 . at", "2020 . at the", ". at the plasma", "at the plasma membrane", "plasma membrane phospho", "membrane phospho mlkl", "phospho mlkl forms heterogeneous", "mlkl forms heterogeneous higher", "forms heterogeneous higher order", "heterogeneous higher order assemblies", "order assemblies which", "assemblies which are", "which are thought to", "are thought to permeabilize", "thought to permeabilize cells", "permeabilize cells leading", "cells leading to", "leading to release of", "to release of damps", "release of damps to", "of damps to invoke", "damps to invoke inflammatory", "to invoke inflammatory responses.", "invoke inflammatory responses. mlkl", "inflammatory responses. mlkl also", "responses. mlkl also exerts", "mlkl also exerts non", "also exerts non necroptotic", "exerts non necroptotic functions", "non necroptotic functions such", "necroptotic functions such as", "functions such as regulation", "such as regulation of", "as regulation of endosomal", "regulation of endosomal trafficking", "of endosomal trafficking or", "endosomal trafficking or mlkl", "trafficking or mlkl induced", "or mlkl induced activation", "mlkl induced activation of", "induced activation of the", "activation of the nlrp3", "of the nlrp3 inflammasome", "nlrp3 inflammasome yoon", "inflammasome yoon s", "yoon s et al.", "s et al. 2017", "al. 2017 shlomovitz", "2017 shlomovitz i", "shlomovitz i et al.", "i et al. 2020", "al. 2020 yoon", "2020 yoon s", "s et al. 2022", "et al. 2022 .", "al. 2022 . while", "2022 . while ripk1", "while ripk1 ripk3", "ripk1 ripk3 and", "ripk3 and mlkl are", "and mlkl are the", "mlkl are the core", "are the core signaling", "the core signaling components", "core signaling components in", "signaling components in the", "components in the necroptosis", "in the necroptosis pathway", "necroptosis pathway many", "pathway many additional", "many additional molecules have", "additional molecules have been", "molecules have been proposed", "have been proposed to", "been proposed to positively", "proposed to positively and", "to positively and negatively", "positively and negatively tune", "and negatively tune the", "negatively tune the signaling", "tune the signaling pathway.", "the signaling pathway. currently", "pathway. currently this", "currently this picture", "this picture is evolving", "picture is evolving rapidly", "is evolving rapidly as", "evolving rapidly as new", "rapidly as new modulators", "as new modulators continue", "new modulators continue to", "modulators continue to be", "continue to be discovered.

the", "to be discovered.

the reactome", "be discovered.

the reactome module", "discovered.

the reactome module describes", "reactome module describes mlkl", "module describes mlkl mediated", "describes mlkl mediated necroptotic", "mlkl mediated necroptotic events", "mediated necroptotic events on", "necroptotic events on the", "events on the plasma", "on the plasma membrane.", "receptor interacting serine/threonine kinase protein", "interacting serine/threonine kinase protein 1", "kinase protein 1 ripk1", "1 ripk1 and", "ripk1 and ripk3 dependent", "and ripk3 dependent necrosis is", "ripk3 dependent necrosis is called", "dependent necrosis is called necroptosis", "necrosis is called necroptosis or", "is called necroptosis or programmed", "called necroptosis or programmed necrosis.", "necroptosis or programmed necrosis. the", "or programmed necrosis. the kinase", "programmed necrosis. the kinase activities", "necrosis. the kinase activities of", "the kinase activities of ripk1", "kinase activities of ripk1 and", "activities of ripk1 and ripk3", "of ripk1 and ripk3 are", "ripk1 and ripk3 are essential", "and ripk3 are essential for", "ripk3 are essential for the", "are essential for the necroptotic", "essential for the necroptotic cell", "for the necroptotic cell death", "the necroptotic cell death in", "necroptotic cell death in human", "death in human mouse", "in human mouse cell", "human mouse cell lines", "mouse cell lines and genetic", "cell lines and genetic mice", "lines and genetic mice models", "genetic mice models cho", "mice models cho ys", "models cho ys et", "cho ys et al. 2009", "et al. 2009 he", "al. 2009 he s", "2009 he s et", "he s et al. 2009", "et al. 2009 2011", "2009 2011 zhang", "2011 zhang dw et", "zhang dw et al. 2009", "et al. 2009 mcquade", "al. 2009 mcquade t", "2009 mcquade t et", "mcquade t et al. 2013", "et al. 2013 newton", "al. 2013 newton et", "2013 newton et al.", "newton et al. 2014 .", "et al. 2014 . the", "al. 2014 . the initiation", "2014 . the initiation of", ". the initiation of necroptosis", "the initiation of necroptosis can", "initiation of necroptosis can be", "of necroptosis can be stimulated", "necroptosis can be stimulated by", "can be stimulated by the", "be stimulated by the same", "stimulated by the same death", "by the same death ligands", "the same death ligands that", "same death ligands that activate", "death ligands that activate extrinsic", "ligands that activate extrinsic apoptotic", "that activate extrinsic apoptotic signaling", "activate extrinsic apoptotic signaling pathway", "apoptotic signaling pathway such", "signaling pathway such as", "pathway such as tumor", "such as tumor necrosis factor", "tumor necrosis factor tnf", "factor tnf alpha", "tnf alpha fas", "fasl and trail", "and trail tnf related", "trail tnf related apoptosis", "tnf related apoptosis inducing ligand", "apoptosis inducing ligand or", "inducing ligand or toll", "ligand or toll like", "or toll like receptors 3", "toll like receptors 3 and", "like receptors 3 and 4", "receptors 3 and 4 ligands", "and 4 ligands holler", "4 ligands holler n", "ligands holler n et", "holler n et al. 2000", "et al. 2000 he", "al. 2000 he s", "2000 he s et", "et al. 2009 feoktistova", "al. 2009 feoktistova m", "2009 feoktistova m et", "feoktistova m et al. 2011", "et al. 2011 voigt", "al. 2011 voigt s", "2011 voigt s et", "voigt s et al. 2014", "s et al. 2014 .", "et al. 2014 . in", "al. 2014 . in contrast", "2014 . in contrast to", ". in contrast to apoptosis", "contrast to apoptosis necroptosis", "to apoptosis necroptosis represents", "apoptosis necroptosis represents a", "necroptosis represents a form of", "represents a form of cell", "a form of cell death", "form of cell death that", "of cell death that is", "cell death that is optimally", "death that is optimally induced", "that is optimally induced when", "is optimally induced when caspases", "optimally induced when caspases are", "induced when caspases are inhibited", "caspases are inhibited holler", "are inhibited holler n", "inhibited holler n et", "et al. 2000 hopkins", "al. 2000 hopkins donaldson", "2000 hopkins donaldson s", "hopkins donaldson s et al.", "donaldson s et al. 2000", "et al. 2000 sawai", "al. 2000 sawai h", "2000 sawai h 2014", "sawai h 2014 . specific", "h 2014 . specific inhibitors", "2014 . specific inhibitors of", ". specific inhibitors of caspase", "specific inhibitors of caspase independent", "inhibitors of caspase independent necrosis", "caspase independent necrosis necrostatins", "necrosis necrostatins have", "necrostatins have recently been", "recently been identified degterev", "been identified degterev a", "identified degterev a et", "degterev a et al. 2005", "et al. 2005 2008", "al. 2005 2008 .", "2005 2008 . necrostatins", "2008 . necrostatins have been", ". necrostatins have been shown", "necrostatins have been shown to", "have been shown to inhibit", "been shown to inhibit the", "shown to inhibit the kinase", "to inhibit the kinase activity", "inhibit the kinase activity of", "the kinase activity of ripk1", "activity of ripk1 degterev", "of ripk1 degterev a", "ripk1 degterev a et", "degterev a et al. 2008", "a et al. 2008 .", "et al. 2008 . importantly", "2008 . importantly cell", ". importantly cell death", "importantly cell death of", "cell death of apoptotic morphology", "death of apoptotic morphology can", "of apoptotic morphology can be", "apoptotic morphology can be shifted", "morphology can be shifted to", "can be shifted to a", "be shifted to a necrotic", "shifted to a necrotic phenotype", "to a necrotic phenotype when", "a necrotic phenotype when caspase", "necrotic phenotype when caspase 8", "phenotype when caspase 8 activity", "when caspase 8 activity is", "caspase 8 activity is compromised", "activity is compromised otherwise", "is compromised otherwise active", "compromised otherwise active caspase", "otherwise active caspase 8 blocks", "active caspase 8 blocks necroptosis", "caspase 8 blocks necroptosis by", "8 blocks necroptosis by the", "blocks necroptosis by the proteolytic", "necroptosis by the proteolytic cleavage", "by the proteolytic cleavage of", "the proteolytic cleavage of ripk1", "proteolytic cleavage of ripk1 and", "cleavage of ripk1 and ripk3", "ripk1 and ripk3 kalai", "and ripk3 kalai m", "ripk3 kalai m et", "kalai m et al. 2002", "et al. 2002 degterev", "al. 2002 degterev a", "2002 degterev a et", "et al. 2008 lin", "al. 2008 lin y", "2008 lin y et", "lin y et al. 1999", "et al. 1999 feng", "al. 1999 feng s", "1999 feng s et", "feng s et al. 2007", "s et al. 2007 .", "et al. 2007 . when", "al. 2007 . when caspase", "2007 . when caspase activity", ". when caspase activity is", "when caspase activity is inhibited", "caspase activity is inhibited under", "activity is inhibited under certain", "is inhibited under certain pathophysiological", "inhibited under certain pathophysiological conditions", "under certain pathophysiological conditions or", "certain pathophysiological conditions or by", "pathophysiological conditions or by pharmacological", "conditions or by pharmacological agents", "by pharmacological agents deubiquitinated", "pharmacological agents deubiquitinated ripk1", "agents deubiquitinated ripk1 is", "deubiquitinated ripk1 is engaged in", "ripk1 is engaged in physical", "is engaged in physical and", "engaged in physical and functional", "in physical and functional interactions", "physical and functional interactions with", "and functional interactions with the", "functional interactions with the cognate", "interactions with the cognate kinase", "with the cognate kinase ripk3", "the cognate kinase ripk3 leading", "cognate kinase ripk3 leading to", "kinase ripk3 leading to formation", "ripk3 leading to formation of", "leading to formation of necrosome", "formation of necrosome a", "of necrosome a necroptosis", "necrosome a necroptosis inducing", "a necroptosis inducing complex consisting", "necroptosis inducing complex consisting of", "inducing complex consisting of ripk1", "complex consisting of ripk1 and", "consisting of ripk1 and ripk3", "ripk1 and ripk3 sawai", "and ripk3 sawai h", "ripk3 sawai h 2013", "sawai h 2013 moquin", "h 2013 moquin dm", "2013 moquin dm et", "moquin dm et al. 2013", "et al. 2013 kalai", "al. 2013 kalai m", "2013 kalai m et", "et al. 2002 cho", "al. 2002 cho ys", "2002 cho ys et", "et al. 2009 zhang", "al. 2009 zhang dw", "2009 zhang dw et", "dw et al. 2009 .", "et al. 2009 . within", "al. 2009 . within the", "2009 . within the necrosome", ". within the necrosome ripk1", "within the necrosome ripk1 and", "the necrosome ripk1 and ripk3", "necrosome ripk1 and ripk3 bind", "ripk1 and ripk3 bind to", "and ripk3 bind to each", "ripk3 bind to each other", "bind to each other through", "to each other through their", "each other through their rip", "other through their rip homotypic", "through their rip homotypic interaction", "their rip homotypic interaction motif", "homotypic interaction motif rhim", "motif rhim domains.", "rhim domains. the rhims", "domains. the rhims can facilitate", "the rhims can facilitate ripk1:ripk3", "rhims can facilitate ripk1:ripk3 oligomerization", "facilitate ripk1:ripk3 oligomerization allowing", "ripk1:ripk3 oligomerization allowing them", "oligomerization allowing them to", "allowing them to form amyloid", "them to form amyloid like", "to form amyloid like fibrillar", "form amyloid like fibrillar structures", "like fibrillar structures li", "fibrillar structures li j", "structures li j et", "li j et al. 2012", "et al. 2012 mompean", "al. 2012 mompean m", "2012 mompean m et", "mompean m et al. 2018", "m et al. 2018 .", "et al. 2018 . ripk3", "al. 2018 . ripk3 in", "2018 . ripk3 in turn", ". ripk3 in turn interacts", "ripk3 in turn interacts with", "in turn interacts with mixed", "turn interacts with mixed lineage", "interacts with mixed lineage kinase", "with mixed lineage kinase domain", "mixed lineage kinase domain like", "lineage kinase domain like protein", "domain like protein mlkl", "mlkl sun l", "sun l et al. 2012", "et al. 2012 zhao", "al. 2012 zhao j", "2012 zhao j et", "zhao j et al. 2012", "et al. 2012 murphy", "al. 2012 murphy jm", "2012 murphy jm et", "murphy jm et al. 2013", "et al. 2013 chen", "al. 2013 chen w", "2013 chen w et", "chen w et al. 2013", "w et al. 2013 .", "et al. 2013 . the", "al. 2013 . the precise", "2013 . the precise mechanism", ". the precise mechanism of", "the precise mechanism of mlkl", "precise mechanism of mlkl activation", "mechanism of mlkl activation by", "of mlkl activation by ripk3", "mlkl activation by ripk3 is", "activation by ripk3 is incompletely", "by ripk3 is incompletely understood", "ripk3 is incompletely understood and", "is incompletely understood and may", "incompletely understood and may vary", "understood and may vary across", "and may vary across species", "vary across species davies", "across species davies ka", "species davies ka et", "davies ka et al. 2020", "ka et al. 2020 .", "et al. 2020 . mouse", "al. 2020 . mouse mlkl", "2020 . mouse mlkl activation", ". mouse mlkl activation relies", "mouse mlkl activation relies on", "mlkl activation relies on transient", "activation relies on transient engagement", "relies on transient engagement of", "on transient engagement of ripk3", "transient engagement of ripk3 to", "engagement of ripk3 to facilitate", "of ripk3 to facilitate phosphorylation", "ripk3 to facilitate phosphorylation of", "to facilitate phosphorylation of the", "facilitate phosphorylation of the pseudokinase", "phosphorylation of the pseudokinase domain", "the pseudokinase domain murphy", "pseudokinase domain murphy jm", "domain murphy jm et", "et al. 2013 petrie", "al. 2013 petrie ej", "2013 petrie ej et", "petrie ej et al. 2019a", "al. 2019a while", "2019a while it", "while it appears that stable", "it appears that stable recruitment", "appears that stable recruitment of", "that stable recruitment of human", "stable recruitment of human mlkl", "recruitment of human mlkl by", "of human mlkl by necrosomal", "human mlkl by necrosomal ripk3", "mlkl by necrosomal ripk3 is", "by necrosomal ripk3 is an", "necrosomal ripk3 is an additional", "ripk3 is an additional crucial", "is an additional crucial step", "an additional crucial step in", "additional crucial step in human", "crucial step in human mlkl", "step in human mlkl activation", "human mlkl activation davies", "mlkl activation davies ka", "activation davies ka et", "davies ka et al. 2018", "et al. 2018 petrie", "al. 2018 petrie ej", "2018 petrie ej et", "petrie ej et al. 2018", "et al. 2018 2019b", "al. 2018 2019b .", "2018 2019b . ripk3", "2019b . ripk3 mediated phosphorylation", ". ripk3 mediated phosphorylation is", "ripk3 mediated phosphorylation is thought", "mediated phosphorylation is thought to", "phosphorylation is thought to initiate", "is thought to initiate mlkl", "thought to initiate mlkl oligomerization", "initiate mlkl oligomerization membrane", "mlkl oligomerization membrane translocation", "oligomerization membrane translocation and", "membrane translocation and membrane disruption", "and membrane disruption sun", "membrane disruption sun l", "disruption sun l et", "et al. 2012 wang", "al. 2012 wang h", "2012 wang h et", "wang h et al. 2014", "et al. 2014 petrie", "al. 2014 petrie ej", "2014 petrie ej et", "petrie ej et al. 2020", "et al. 2020 samson", "al. 2020 samson al", "2020 samson al et", "samson al et al. 2020", "al et al. 2020 .", "et al. 2020 . studies", "al. 2020 . studies in", "2020 . studies in human", ". studies in human cell", "studies in human cell lines", "in human cell lines suggest", "human cell lines suggest that", "cell lines suggest that upon", "lines suggest that upon induction", "suggest that upon induction of", "that upon induction of necroptosis", "upon induction of necroptosis mlkl", "induction of necroptosis mlkl shifts", "of necroptosis mlkl shifts to", "necroptosis mlkl shifts to the", "mlkl shifts to the plasma", "shifts to the plasma membrane", "to the plasma membrane and", "the plasma membrane and membranous", "plasma membrane and membranous organelles", "membrane and membranous organelles such", "and membranous organelles such as", "membranous organelles such as mitochondria", "such as mitochondria lysosome", "mitochondria lysosome endosome", "lysosome endosome and er", "endosome and er wang", "and er wang h", "er wang h et", "al. 2014 but", "2014 but it", "but it is trafficking via", "it is trafficking via a", "is trafficking via a golgi", "trafficking via a golgi microtubule", "via a golgi microtubule actin", "a golgi microtubule actin dependent", "golgi microtubule actin dependent mechanism", "microtubule actin dependent mechanism that", "actin dependent mechanism that facilitates", "dependent mechanism that facilitates plasma", "mechanism that facilitates plasma membrane", "that facilitates plasma membrane translocation", "plasma membrane translocation where", "membrane translocation where membrane", "translocation where membrane disruption", "where membrane disruption causes death", "disruption causes death samson", "causes death samson al", "death samson al et", "et al. 2020 . the", "al. 2020 . the mechanisms", "2020 . the mechanisms of", ". the mechanisms of necroptosis", "the mechanisms of necroptosis regulation", "mechanisms of necroptosis regulation and", "of necroptosis regulation and execution", "necroptosis regulation and execution downstream", "regulation and execution downstream of", "and execution downstream of mlkl", "execution downstream of mlkl remain", "downstream of mlkl remain elusive.", "of mlkl remain elusive. the", "mlkl remain elusive. the precise", "remain elusive. the precise oligomeric", "elusive. the precise oligomeric form", "the precise oligomeric form of", "precise oligomeric form of mlkl", "oligomeric form of mlkl that", "form of mlkl that mediates", "of mlkl that mediates plasma", "mlkl that mediates plasma membrane", "that mediates plasma membrane disruption", "mediates plasma membrane disruption has", "plasma membrane disruption has been", "membrane disruption has been highly", "disruption has been highly debated", "been highly debated cai", "highly debated cai z", "debated cai z et", "cai z et al. 2014", "et al. 2014 chen", "al. 2014 chen x", "2014 chen x et", "chen x et al. 2014", "et al. 2014 dondelinger", "al. 2014 dondelinger y", "2014 dondelinger y et", "dondelinger y et al. 2014", "et al. 2014 wang", "al. 2014 wang h", "2014 wang h et", "petrie ej et al. 2017", "et al. 2017 2018", "2017 2018 samson", "2018 samson al et", "al. 2020 . however", ". however microscopy data", "however microscopy data revealed", "microscopy data revealed that mlkl", "data revealed that mlkl assembles", "revealed that mlkl assembles into", "that mlkl assembles into higher", "mlkl assembles into higher molecular", "assembles into higher molecular weight", "into higher molecular weight species", "higher molecular weight species upon", "molecular weight species upon cytoplasmic", "weight species upon cytoplasmic necrosomes", "species upon cytoplasmic necrosomes within", "upon cytoplasmic necrosomes within human", "cytoplasmic necrosomes within human cells", "within human cells and", "human cells and upon", "cells and upon phosphorylation", "and upon phosphorylation by ripk3", "phosphorylation by ripk3 mlkl", "by ripk3 mlkl is", "ripk3 mlkl is trafficked", "mlkl is trafficked to the", "is trafficked to the plasma", "trafficked to the plasma membrane", "the plasma membrane samson", "plasma membrane samson al", "membrane samson al et", "et al. 2020 . at", "al. 2020 . at the", "2020 . at the plasma", ". at the plasma membrane", "the plasma membrane phospho", "plasma membrane phospho mlkl", "membrane phospho mlkl forms", "phospho mlkl forms heterogeneous higher", "mlkl forms heterogeneous higher order", "forms heterogeneous higher order assemblies", "higher order assemblies which", "order assemblies which are", "assemblies which are thought", "which are thought to permeabilize", "are thought to permeabilize cells", "to permeabilize cells leading", "permeabilize cells leading to", "cells leading to release", "leading to release of damps", "to release of damps to", "release of damps to invoke", "of damps to invoke inflammatory", "damps to invoke inflammatory responses.", "to invoke inflammatory responses. mlkl", "invoke inflammatory responses. mlkl also", "inflammatory responses. mlkl also exerts", "responses. mlkl also exerts non", "mlkl also exerts non necroptotic", "also exerts non necroptotic functions", "exerts non necroptotic functions such", "non necroptotic functions such as", "necroptotic functions such as regulation", "functions such as regulation of", "such as regulation of endosomal", "as regulation of endosomal trafficking", "regulation of endosomal trafficking or", "of endosomal trafficking or mlkl", "endosomal trafficking or mlkl induced", "trafficking or mlkl induced activation", "or mlkl induced activation of", "mlkl induced activation of the", "induced activation of the nlrp3", "activation of the nlrp3 inflammasome", "the nlrp3 inflammasome yoon", "nlrp3 inflammasome yoon s", "inflammasome yoon s et", "yoon s et al. 2017", "et al. 2017 shlomovitz", "al. 2017 shlomovitz i", "2017 shlomovitz i et", "shlomovitz i et al. 2020", "et al. 2020 yoon", "al. 2020 yoon s", "2020 yoon s et", "yoon s et al. 2022", "s et al. 2022 .", "et al. 2022 . while", "al. 2022 . while ripk1", ". while ripk1 ripk3", "while ripk1 ripk3 and", "ripk1 ripk3 and mlkl", "ripk3 and mlkl are the", "and mlkl are the core", "mlkl are the core signaling", "are the core signaling components", "the core signaling components in", "core signaling components in the", "signaling components in the necroptosis", "components in the necroptosis pathway", "the necroptosis pathway many", "necroptosis pathway many additional", "pathway many additional molecules", "many additional molecules have been", "additional molecules have been proposed", "molecules have been proposed to", "have been proposed to positively", "been proposed to positively and", "proposed to positively and negatively", "to positively and negatively tune", "positively and negatively tune the", "and negatively tune the signaling", "negatively tune the signaling pathway.", "tune the signaling pathway. currently", "signaling pathway. currently this", "pathway. currently this picture", "currently this picture is", "this picture is evolving rapidly", "picture is evolving rapidly as", "is evolving rapidly as new", "evolving rapidly as new modulators", "rapidly as new modulators continue", "as new modulators continue to", "new modulators continue to be", "modulators continue to be discovered.

the", "continue to be discovered.

the reactome", "to be discovered.

the reactome module", "be discovered.

the reactome module describes", "discovered.

the reactome module describes mlkl", "reactome module describes mlkl mediated", "module describes mlkl mediated necroptotic", "describes mlkl mediated necroptotic events", "mlkl mediated necroptotic events on", "mediated necroptotic events on the", "necroptotic events on the plasma", "events on the plasma membrane." ] }, { "record_id": "GLY_000594_1_411", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5218900", "r hsa", "hsa 5218900", "r hsa 5218900" ] }, { "record_id": "GLY_000594_1_411", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "casp8 activity", "activity is", "is inhibited", "casp8 activity is", "activity is inhibited", "casp8 activity is inhibited", "cell death", "death triggered", "triggered by", "by extrinsic", "extrinsic stimuli", "stimuli via", "via death", "death receptors", "receptors or", "or toll", "toll like", "like receptors", "may result", "result in", "in either", "either 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al. 2002 . the", "al. 2002 . the proteolytic", "2002 . the proteolytic activity", ". the proteolytic activity of", "the proteolytic activity of a", "proteolytic activity of a fully", "activity of a fully processed", "a fully processed heterotetrameric", "fully processed heterotetrameric form", "processed heterotetrameric form of", "heterotetrameric form of casp8 in", "form of casp8 in human", "of casp8 in human and", "casp8 in human and rodent", "in human and rodent cells", "human and rodent cells is", "and rodent cells is required", "rodent cells is required for", "cells is required for proapoptotic", "is required for proapoptotic signaling", "required for proapoptotic signaling and", "for proapoptotic signaling and also", "proapoptotic signaling and also for", "signaling and also for a", "and also for a cleavage", "also for a cleavage of", "for a cleavage of kinases", "a cleavage of kinases ripk1", "cleavage of kinases ripk1 and", "of kinases ripk1 and ripk3", "ripk1 and ripk3 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caspase inhibitors", "presence of caspase inhibitors such", "of caspase inhibitors such as", "caspase inhibitors such as z", "inhibitors such as z vad", "such as z vad fmk", "z vad fmk pan", "vad fmk pan caspase", "fmk pan caspase inhibitor", "caspase inhibitor endogenous", "inhibitor endogenous flip", "endogenous flip s or", "flip s or viral", "s or viral flip", "or viral flip like protein", "viral flip like protein was", "flip like protein was found", "like protein was found to", "protein was found to switch", "was found to switch signaling", "found to switch signaling to", "to switch signaling to necrotic", "switch signaling to necrotic cell", "signaling to necrotic cell death", "necrotic cell death thome", "cell death thome m", "death thome m et", "thome m et al. 1997", "et al. 1997 kalai", "al. 1997 kalai m", "1997 kalai m et", "et al. 2002 feoktistova", "al. 2002 feoktistova m", "2002 feoktistova m et", "feoktistova m et al. 2011", "et al. 2011 sawai", "al. 2011 sawai h", "2011 sawai h 2013" ] }, { "record_id": "GLY_000594_1_412", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5250924", "r hsa", "hsa 5250924", "r hsa 5250924" ] }, { "record_id": "GLY_000594_1_412", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "b wich", "wich complex", "complex positively", "positively regulates", "regulates rrna", "rrna expression", "b wich complex", "wich complex positively", "complex positively regulates", "positively regulates rrna", "regulates rrna expression", "b wich complex positively", "wich complex positively regulates", "complex positively regulates rrna", "positively regulates rrna expression", "b wich complex positively regulates", "wich complex positively regulates rrna", "complex positively regulates rrna expression", "the b", "complex is", "is a", "a large", "large 3", "3 mdalton", "mdalton complex", "complex containing", "containing smarca5", "nuclear myosin", 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is", "b wich is found", "wich is found at", "is found at active", "found at active rrna", "at active rrna genes", "active rrna genes as", "rrna genes as well", "genes as well as", "as well as at", "well as at 5s", "as at 5s rrna", "at 5s rrna and", "5s rrna and 7sl", "rrna and 7sl rna", "and 7sl rna genes.", "7sl rna genes. b", "rna genes. b wich", "genes. b wich appears", "b wich appears to", "wich appears to remodel", "appears to remodel chromatin", "to remodel chromatin and", "remodel chromatin and recruit", "chromatin and recruit histone", "and recruit histone acetyltransferases", "recruit histone acetyltransferases that", "histone acetyltransferases that modify", "acetyltransferases that modify histones", "that modify histones to", "modify histones to transcriptionally", "histones to transcriptionally active", "to transcriptionally active states.", "the b wich complex is", "b wich complex is a", "wich complex is a large", "complex is a large 3", "is a large 3 mdalton", "a large 3 mdalton complex", "large 3 mdalton complex containing", "3 mdalton complex containing smarca5", "complex containing smarca5 snf2h", "myo1c nuclear myosin 1c", "myosin 1c sf3b1", "sf3b1 dek mybbp1a", "dek mybbp1a and", "and ddx21 cavellan et", "ddx21 cavellan et al.", "et al. 2006 percipalle", "al. 2006 percipalle et", "2006 percipalle et al.", "et al. 2006 vintermist", "al. 2006 vintermist et", "2006 vintermist et al.", "et al. 2001 sarshad", "al. 2001 sarshad et", "2001 sarshad et al.", "et al. 2013 shen", "al. 2013 shen et", "2013 shen et al.", "et al. 2013 reviewed", "al. 2013 reviewed in", "2013 reviewed in percipalle", "reviewed in percipalle and farrants", "in percipalle and farrants 2006", "percipalle and farrants 2006 .", "and farrants 2006 . b", "farrants 2006 . b wich", "2006 . b wich is", ". b wich is found", "b wich is found at", "wich is found at active", "is found at active rrna", "found at active rrna genes", "at active rrna genes as", "active rrna genes as well", "rrna genes as well as", "genes as well as at", "as well as at 5s", "well as at 5s rrna", "as at 5s rrna and", "at 5s rrna and 7sl", "5s rrna and 7sl rna", "rrna and 7sl rna genes.", "and 7sl rna genes. b", "7sl rna genes. b wich", "rna genes. b wich appears", "genes. b wich appears to", "b wich appears to remodel", "wich appears to remodel chromatin", "appears to remodel chromatin and", "to remodel chromatin and recruit", "remodel chromatin and recruit histone", "chromatin and recruit histone acetyltransferases", "and recruit histone acetyltransferases that", "recruit histone acetyltransferases that modify", "histone acetyltransferases that modify histones", "acetyltransferases that modify histones to", "that modify histones to transcriptionally", "modify histones to transcriptionally active", "histones to transcriptionally active states." ] }, { "record_id": "GLY_000594_1_413", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "525793", "r hsa", "hsa 525793", "r hsa 525793" ] }, { "record_id": "GLY_000594_1_413", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "the formation", "formation of", "of muscle", "muscle tissue", "is a", "a complex", "complex process", "process involving", "involving steps", "steps of", "of cell", "cell proliferation", "proliferation mediated", "mediated by", "by growth", "growth factor", "factor signaling", "cell differentiation", "reorganization of", "of cells", "cells to", "to form", "form myotubes", "and cell", "cell fusion.", "fusion. here", "one regulatory", "regulatory feature", "feature of", "of this", "this process", "process has", "has been", "been annotated", "the signaling", "signaling cascade", "cascade initiated", "initiated by", "by cdo", "cell adhesion", "adhesion molecule", "molecule related/downregulated", "related/downregulated by", "by oncogenes", "and associated", "associated co", "co receptors.

cdo/cdon", "receptors.

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myogenic", "
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cdo/cdon", "co receptors.

cdo/cdon is", "receptors.

cdo/cdon is a", "is a type", "a type i", "type i transmembrane", "i transmembrane multifunctional", "transmembrane multifunctional co", "multifunctional co receptor", "co receptor consisting", "receptor consisting of", "consisting of five", "of five immunoglobulin", "five immunoglobulin and", "immunoglobulin and three", "and three fibronectin", "three fibronectin type", "fibronectin type iii", "iii fniii", "fniii repeats", "repeats in the", "in the extracellular", "the extracellular domain", "domain and", "and an intracellular", "an intracellular domain", "intracellular domain with", "domain with no", "with no identifiable", "no identifiable motifs.", "identifiable motifs. it", "motifs. it has", "it has been", "has been implicated", "been implicated in", "implicated in enhancing", "in enhancing muscle", "enhancing muscle differentiation", "muscle differentiation in", "differentiation in promyogenic", "in promyogenic cells.", "promyogenic cells. cdo", "cells. cdo exert", "cdo exert its", "exert its promyogenic", "its promyogenic effects", "promyogenic effects as", "effects as a", "as a component", "a component of", "component of multiprotein", "of multiprotein complexes", "multiprotein complexes that", "complexes that include", "that include the", "include the closely", "the closely related", "closely related factor", "related factor boc", "boc the", "the ig superfamily", "ig superfamily receptor", "superfamily receptor neogenin", "receptor neogenin and", "neogenin and its", "and its ligand", "its ligand netrin", "ligand netrin 3", "3 and", "and the adhesion", "the adhesion molecules", "adhesion molecules n", "n and", "and m cadherin.", "m cadherin. cdo", "cadherin. cdo modulates", "cdo modulates the", "modulates the cdc42", "the cdc42 and", "cdc42 and p38", "and p38 mitogen", "p38 mitogen activated", "mitogen activated protein", "activated protein kinase", "kinase mapk", "mapk pathways", "pathways via a", "via a direct", "a direct association", "direct association with", "association with two", "with two scaffold", "two scaffold type", "scaffold type proteins", "proteins jlp", "jlp and bnip", "and bnip 2", "2 to", "to regulate activities", "regulate activities of", "activities of myogenic", "of myogenic bhlh", "myogenic bhlh factors", "bhlh factors and", "factors and myogenic", "and myogenic differentiation.", "myogenic differentiation. cdo", "differentiation. cdo activates", "cdo activates myogenic", "activates myogenic bhlh", "bhlh factors via", "factors via enhanced", "via enhanced heterodimer", "enhanced heterodimer formation", "formation most", "most likely by", "likely by inducing", "by inducing hyper", "inducing hyper phosphorylation", "hyper phosphorylation of", "phosphorylation of e", "of e proteins.", "e proteins.
myogenic", "proteins.
myogenic basic", "
myogenic basic helix", "basic helix loop", "helix loop helix", "helix bhlh", "proteins are master", "are master regulatory", "master regulatory proteins", "regulatory proteins that", "proteins that activate", "that activate the", "activate the transcription", "the transcription of", "transcription of many", "of many muscle", "many muscle specific", "muscle specific genes", "specific genes during", "genes during myogenesis.", "during myogenesis. these", "myogenesis. these myogenic", "these myogenic bhlh", "myogenic bhlh proteins", "bhlh proteins also", "proteins also referred", "also referred to", "referred to as", "to as myod", "as myod family", "myod family includes", "family includes four", "includes four members", "members myod", "myod myogenin", "myogenin myf5", "myf5 and mrf4.", "and mrf4. these", "mrf4. these myogenic", "these myogenic factors", "myogenic factors dimerize", "factors dimerize with", "dimerize with e", "with e proteins", "e proteins such", "proteins such as", "such as e12/e47", "e12/e47 itf", "itf 2 and", "2 and heb", "and heb to", "heb to form", "to form heterodimeric", "form heterodimeric complexes", "heterodimeric complexes that", "complexes that bind", "that bind to", "bind to a", "to a conserved", "a conserved dna", "conserved dna sequence", "dna sequence known", "sequence known as", "known as the", "as the e", "the e box", "box which", "which is present", "is present in", "present in the", "in the promoters", "the promoters and", "promoters and enhancers", "and enhancers of", "enhancers of most", "of most muscle", "most muscle specific", "muscle specific genes.", "specific genes. myocyte", "genes. myocyte enhancer", "myocyte enhancer binding", "enhancer binding factor", "binding factor 2", "2 mef2", "which is a", "is a member", "a member of", "member of the", "of the mads", "the mads box", "mads box family", "family also", "also plays an", "plays an important", "an important role", "important role in", "role in muscle", "in muscle differentiation.", "muscle differentiation. mef2", "differentiation. mef2 activates", "mef2 activates transcription", "activates transcription by", "transcription by binding", "by binding to", "binding to the", "to the consensus", "the consensus sequence", "sequence called", "called the mef2", "the mef2 binding", "mef2 binding site", "site which", "which is also", "is also found", "also found in", "found in the", "in the control", "the control regions", "control regions of", "regions of numerous", "of numerous muscle", "numerous muscle specific", "specific genes. mef2", "genes. mef2 and", "mef2 and myogenic", "and myogenic bhlh", "bhlh proteins synergistically", "proteins synergistically activate", "synergistically activate expression", "activate expression of", "expression of muscle", "of muscle specific", "specific genes via", "genes via protein", "via protein protein", "protein protein interactions", "protein interactions between", "interactions between dna", "between dna binding", "dna binding domains", "binding domains of", "domains of these", "of these heterologous", "these heterologous classes", "heterologous classes of", "classes of transcription", "of transcription factors.", "transcription factors. members", "factors. members of", "members of the", "of the myod", "the myod and", "myod and mef2", "and mef2 family", "mef2 family of", "family of transcription", "of transcription factors", "transcription factors associate", "factors associate combinatorially", "associate combinatorially to", "combinatorially to control", "to control myoblast", "control myoblast specification", "specification differentiation", "differentiation and proliferation.", "myogenesis the formation", "the formation of muscle", "formation of muscle tissue", "muscle tissue is", "tissue is a", "is a complex process", "a complex process involving", "complex process involving steps", "process involving steps of", "involving steps of cell", "steps of cell proliferation", "of cell proliferation mediated", "cell proliferation mediated by", "proliferation mediated by growth", "mediated by growth factor", "by growth factor signaling", "factor signaling cell", "signaling cell differentiation", "cell differentiation reorganization", "differentiation reorganization of", "reorganization of cells to", "of cells to form", "cells to form myotubes", "form myotubes and", "myotubes and cell", "and cell fusion. here", "fusion. here one", "here one regulatory", "one regulatory feature of", "regulatory feature of this", "feature of this process", "of this process has", "this process has been", "process has been annotated", "been annotated the", "annotated the signaling", "the signaling cascade initiated", "signaling cascade initiated by", "cascade initiated by cdo", "by cdo cell", "cdo cell adhesion", "cell adhesion molecule related/downregulated", "adhesion molecule related/downregulated by", "molecule related/downregulated by oncogenes", "by oncogenes and", "oncogenes and associated", "and associated co receptors.

cdo/cdon", "associated co receptors.

cdo/cdon is", "co receptors.

cdo/cdon is a", "receptors.

cdo/cdon is a type", "is a type i", "a type i transmembrane", "type i transmembrane multifunctional", "i transmembrane multifunctional co", "transmembrane multifunctional co receptor", "multifunctional co receptor consisting", "co receptor consisting of", "receptor consisting of five", "consisting of five immunoglobulin", "of five immunoglobulin and", "five immunoglobulin and three", "immunoglobulin and three fibronectin", "and three fibronectin type", "three fibronectin type iii", "type iii fniii", "fniii repeats in", "repeats in the extracellular", "in the extracellular domain", "extracellular domain and", "domain and an", "and an intracellular domain", "an intracellular domain with", "intracellular domain with no", "domain with no identifiable", "with no identifiable motifs.", "no identifiable motifs. it", "identifiable motifs. it has", "motifs. it has been", "it has been implicated", "has been implicated in", "been implicated in enhancing", "implicated in enhancing muscle", "in enhancing muscle differentiation", "enhancing muscle differentiation in", "muscle differentiation in promyogenic", "differentiation in promyogenic cells.", "in promyogenic cells. cdo", "promyogenic cells. cdo exert", "cells. cdo exert its", "cdo exert its promyogenic", "exert its promyogenic effects", "its promyogenic effects as", "promyogenic effects as a", "effects as a component", "as a component of", "a component of multiprotein", "component of multiprotein complexes", "of multiprotein complexes that", "multiprotein complexes that include", "complexes that include the", "that include the closely", "include the closely related", "the closely related factor", "closely related factor boc", "factor boc the", "boc the ig", "the ig superfamily receptor", "ig superfamily receptor neogenin", "superfamily receptor neogenin and", "receptor neogenin and its", "neogenin and its ligand", "and its ligand netrin", "its ligand netrin 3", "netrin 3 and", "3 and the", "and the adhesion molecules", "the adhesion molecules n", "molecules n and", "n and m", "and m cadherin. cdo", "m cadherin. cdo modulates", "cadherin. cdo modulates the", "cdo modulates the cdc42", "modulates the cdc42 and", "the cdc42 and p38", "cdc42 and p38 mitogen", "and p38 mitogen activated", "p38 mitogen activated protein", "mitogen activated protein kinase", "protein kinase mapk", "mapk pathways via", "pathways via a direct", "via a direct association", "a direct association with", "direct association with two", "association with two scaffold", "with two scaffold type", "two scaffold type proteins", "type proteins jlp", "proteins jlp and", "jlp and bnip 2", "bnip 2 to", "2 to regulate", "to regulate activities of", "regulate activities of myogenic", "activities of myogenic bhlh", "of myogenic bhlh factors", "myogenic bhlh factors and", "bhlh factors and myogenic", "factors and myogenic differentiation.", "and myogenic differentiation. cdo", "myogenic differentiation. cdo activates", "differentiation. cdo activates myogenic", "cdo activates myogenic bhlh", "activates myogenic bhlh factors", "myogenic bhlh factors via", "bhlh factors via enhanced", "factors via enhanced heterodimer", "via enhanced heterodimer formation", "heterodimer formation most", "formation most likely", "most likely by inducing", "likely by inducing hyper", "by inducing hyper phosphorylation", "inducing hyper phosphorylation of", "hyper phosphorylation of e", "phosphorylation of e proteins.", "of e proteins.
myogenic", "e proteins.
myogenic basic", "proteins.
myogenic basic helix", "
myogenic basic helix loop", "basic helix loop helix", "loop helix bhlh", "bhlh proteins are", "proteins are master regulatory", "are master regulatory proteins", "master regulatory proteins that", "regulatory proteins that activate", "proteins that activate the", "that activate the transcription", "activate the transcription of", "the transcription of many", "transcription of many muscle", "of many muscle specific", "many muscle specific genes", "muscle specific genes during", "specific genes during myogenesis.", "genes during myogenesis. these", "during myogenesis. these myogenic", "myogenesis. these myogenic bhlh", "these myogenic bhlh proteins", "myogenic bhlh proteins also", "bhlh proteins also referred", "proteins also referred to", "also referred to as", "referred to as myod", "to as myod family", "as myod family includes", "myod family includes four", "family includes four members", "four members myod", "myogenin myf5 and", "myf5 and mrf4. these", "and mrf4. these myogenic", "mrf4. these myogenic factors", "these myogenic factors dimerize", "myogenic factors dimerize with", "factors dimerize with e", "dimerize with e proteins", "with e proteins such", "e proteins such as", "proteins such as e12/e47", "as e12/e47 itf", "e12/e47 itf 2", "itf 2 and heb", "2 and heb to", "and heb to form", "heb to form heterodimeric", "to form heterodimeric complexes", "form heterodimeric complexes that", "heterodimeric complexes that bind", "complexes that bind to", "that bind to a", "bind to a conserved", "to a conserved dna", "a conserved dna sequence", "conserved dna sequence known", "dna sequence known as", "sequence known as the", "known as the e", "as the e box", "e box which", "box which is", "which is present in", "is present in the", "present in the promoters", "in the promoters and", "the promoters and enhancers", "promoters and enhancers of", "and enhancers of most", "enhancers of most muscle", "of most muscle specific", "most muscle specific genes.", "muscle specific genes. myocyte", "specific genes. myocyte enhancer", "genes. myocyte enhancer binding", "myocyte enhancer binding factor", "enhancer binding factor 2", "factor 2 mef2", "mef2 which", "which is a member", "is a member of", "a member of the", "member of the mads", "of the mads box", "the mads box family", "box family also", "family also plays", "also plays an important", "plays an important role", "an important role in", "important role in muscle", "role in muscle differentiation.", "in muscle differentiation. mef2", "muscle differentiation. mef2 activates", "differentiation. mef2 activates transcription", "mef2 activates transcription by", "activates transcription by binding", "transcription by binding to", "by binding to the", "binding to the consensus", "to the consensus sequence", "consensus sequence called", "sequence called the", "called the mef2 binding", "the mef2 binding site", "binding site which", "site which is", "which is also found", "is also found in", "also found in the", "found in the control", "in the control regions", "the control regions of", "control regions of numerous", "regions of numerous muscle", "of numerous muscle specific", "numerous muscle specific genes.", "muscle specific genes. mef2", "specific genes. mef2 and", "genes. mef2 and myogenic", "mef2 and myogenic bhlh", "and myogenic bhlh proteins", "myogenic bhlh proteins synergistically", "bhlh proteins synergistically activate", "proteins synergistically activate expression", "synergistically activate expression of", "activate expression of muscle", "expression of muscle specific", "of muscle specific genes", "muscle specific genes via", "specific genes via protein", "genes via protein protein", "via protein protein interactions", "protein protein interactions between", "protein interactions between dna", "interactions between dna binding", "between dna binding domains", "dna binding domains of", "binding domains of these", "domains of these heterologous", "of these heterologous classes", "these heterologous classes of", "heterologous classes of transcription", "classes of transcription factors.", "of transcription factors. members", "transcription factors. members of", "factors. members of the", "members of the myod", "of the myod and", "the myod and mef2", "myod and mef2 family", "and mef2 family of", "mef2 family of transcription", "family of transcription factors", "of transcription factors associate", "transcription factors associate combinatorially", "factors associate combinatorially to", "associate combinatorially to control", "combinatorially to control myoblast", "to control myoblast specification", "myoblast specification differentiation", "specification differentiation and", "myogenesis the formation of", "the formation of muscle tissue", "of muscle tissue is", "muscle tissue is a", "tissue is a complex", "is a complex process involving", "a complex process involving steps", "complex process involving steps of", "process involving steps of cell", "involving steps of cell proliferation", "steps of cell proliferation mediated", "of cell proliferation mediated by", "cell proliferation mediated by growth", "proliferation mediated by growth factor", "mediated by growth factor signaling", "growth factor signaling cell", "factor signaling cell differentiation", "cell differentiation reorganization of", "differentiation reorganization of cells", "reorganization of cells to form", "of cells to form myotubes", "to form myotubes and", "form myotubes and cell", "myotubes and cell fusion.", "cell fusion. here one", "fusion. here one regulatory", "here one regulatory feature", "one regulatory feature of this", "regulatory feature of this process", "feature of this process has", "of this process has been", "this process has been annotated", "has been annotated the", "been annotated the signaling", "annotated the signaling cascade", "the signaling cascade initiated by", "signaling cascade initiated by cdo", "initiated by cdo cell", "by cdo cell adhesion", "cdo cell adhesion molecule", "cell adhesion molecule related/downregulated by", "adhesion molecule related/downregulated by oncogenes", "related/downregulated by oncogenes and", "by oncogenes and associated", "oncogenes and associated co", "and associated co receptors.

cdo/cdon is", "associated co receptors.

cdo/cdon is a", "co receptors.

cdo/cdon is a type", "receptors.

cdo/cdon is a type i", "is a type i transmembrane", "a type i transmembrane multifunctional", "type i transmembrane multifunctional co", "i transmembrane multifunctional co receptor", "transmembrane multifunctional co receptor consisting", "multifunctional co receptor consisting of", "co receptor consisting of five", "receptor consisting of five immunoglobulin", "consisting of five immunoglobulin and", "of five immunoglobulin and three", "five immunoglobulin and three fibronectin", "immunoglobulin and three fibronectin type", "and three fibronectin type iii", "fibronectin type iii fniii", "iii fniii repeats", "fniii repeats in the", "repeats in the extracellular domain", "the extracellular domain and", "extracellular domain and an", "domain and an intracellular", "and an intracellular domain with", "an intracellular domain with no", "intracellular domain with no identifiable", "domain with no identifiable motifs.", "with no identifiable motifs. it", "no identifiable motifs. it has", "identifiable motifs. it has been", "motifs. it has been implicated", "it has been implicated in", "has been implicated in enhancing", "been implicated in enhancing muscle", "implicated in enhancing muscle differentiation", "in enhancing muscle differentiation in", "enhancing muscle differentiation in promyogenic", "muscle differentiation in promyogenic cells.", "differentiation in promyogenic cells. cdo", "in promyogenic cells. cdo exert", "promyogenic cells. cdo exert its", "cells. cdo exert its promyogenic", "cdo exert its promyogenic effects", "exert its promyogenic effects as", "its promyogenic effects as a", "promyogenic effects as a component", "effects as a component of", "as a component of multiprotein", "a component of multiprotein complexes", "component of multiprotein complexes that", "of multiprotein complexes that include", "multiprotein complexes that include the", "complexes that include the closely", "that include the closely related", "include the closely related factor", "the closely related factor boc", "related factor boc the", "factor boc the ig", "boc the ig superfamily", "the ig superfamily receptor neogenin", "ig superfamily receptor neogenin and", "superfamily receptor neogenin and its", "receptor neogenin and its ligand", "neogenin and its ligand netrin", "and its ligand netrin 3", "ligand netrin 3 and", "netrin 3 and the", "3 and the adhesion", "and the adhesion molecules n", "adhesion molecules n and", "molecules n and m", "n and m cadherin.", "and m cadherin. cdo modulates", "m cadherin. cdo modulates the", "cadherin. cdo modulates the cdc42", "cdo modulates the cdc42 and", "modulates the cdc42 and p38", "the cdc42 and p38 mitogen", "cdc42 and p38 mitogen activated", "and p38 mitogen activated protein", "p38 mitogen activated protein kinase", "activated protein kinase mapk", "kinase mapk pathways", "mapk pathways via a", "pathways via a direct association", "via a direct association with", "a direct association with two", "direct association with two scaffold", "association with two scaffold type", "with two scaffold type proteins", "scaffold type proteins jlp", "type proteins jlp and", "proteins jlp and bnip", "and bnip 2 to", "bnip 2 to regulate", "2 to regulate activities", "to regulate activities of myogenic", "regulate activities of myogenic bhlh", "activities of myogenic bhlh factors", "of myogenic bhlh factors and", "myogenic bhlh factors and myogenic", "bhlh factors and myogenic differentiation.", "factors and myogenic differentiation. cdo", "and myogenic differentiation. cdo activates", "myogenic differentiation. cdo activates myogenic", "differentiation. cdo activates myogenic bhlh", "cdo activates myogenic bhlh factors", "activates myogenic bhlh factors via", "myogenic bhlh factors via enhanced", "bhlh factors via enhanced heterodimer", "factors via enhanced heterodimer formation", "enhanced heterodimer formation most", "heterodimer formation most likely", "formation most likely by", "most likely by inducing hyper", "likely by inducing hyper phosphorylation", "by inducing hyper phosphorylation of", "inducing hyper phosphorylation of e", "hyper phosphorylation of e proteins.", "phosphorylation of e proteins.
myogenic", "of e proteins.
myogenic basic", "e proteins.
myogenic basic helix", "proteins.
myogenic basic helix loop", "
myogenic basic helix loop helix", "helix loop helix bhlh", "helix bhlh proteins", "bhlh proteins are master", "proteins are master regulatory proteins", "are master regulatory proteins that", "master regulatory proteins that activate", "regulatory proteins that activate the", "proteins that activate the transcription", "that activate the transcription of", "activate the transcription of many", "the transcription of many muscle", "transcription of many muscle specific", "of many muscle specific genes", "many muscle specific genes during", "muscle specific genes during myogenesis.", "specific genes during myogenesis. these", "genes during myogenesis. these myogenic", "during myogenesis. these myogenic bhlh", "myogenesis. these myogenic bhlh proteins", "these myogenic bhlh proteins also", "myogenic bhlh proteins also referred", "bhlh proteins also referred to", "proteins also referred to as", "also referred to as myod", "referred to as myod family", "to as myod family includes", "as myod family includes four", "myod family includes four members", "includes four members myod", "members myod myogenin", "myod myogenin myf5", "myogenin myf5 and mrf4.", "myf5 and mrf4. these myogenic", "and mrf4. these myogenic factors", "mrf4. these myogenic factors dimerize", "these myogenic factors dimerize with", "myogenic factors dimerize with e", "factors dimerize with e proteins", "dimerize with e proteins such", "with e proteins such as", "e proteins such as e12/e47", "such as e12/e47 itf", "as e12/e47 itf 2", "e12/e47 itf 2 and", "itf 2 and heb to", "2 and heb to form", "and heb to form heterodimeric", "heb to form heterodimeric complexes", "to form heterodimeric complexes that", "form heterodimeric complexes that bind", "heterodimeric complexes that bind to", "complexes that bind to a", "that bind to a conserved", "bind to a conserved dna", "to a conserved dna sequence", "a conserved dna sequence known", "conserved dna sequence known as", "dna sequence known as the", "sequence known as the e", "known as the e box", "the e box which", "e box which is", "box which is present", "which is present in the", "is present in the promoters", "present in the promoters and", "in the promoters and enhancers", "the promoters and enhancers of", "promoters and enhancers of most", "and enhancers of most muscle", "enhancers of most muscle specific", "of most muscle specific genes.", "most muscle specific genes. myocyte", "muscle specific genes. myocyte enhancer", "specific genes. myocyte enhancer binding", "genes. myocyte enhancer binding factor", "myocyte enhancer binding factor 2", "binding factor 2 mef2", "mef2 which is", "which is a member of", "is a member of the", "a member of the mads", "member of the mads box", "of the mads box family", "mads box family also", "box family also plays", "family also plays an", "also plays an important role", "plays an important role in", "an important role in muscle", "important role in muscle differentiation.", "role in muscle differentiation. mef2", "in muscle differentiation. mef2 activates", "muscle differentiation. mef2 activates transcription", "differentiation. mef2 activates transcription by", "mef2 activates transcription by binding", "activates transcription by binding to", "transcription by binding to the", "by binding to the consensus", "binding to the consensus sequence", "the consensus sequence called", "consensus sequence called the", "sequence called the mef2", "called the mef2 binding site", "mef2 binding site which", "binding site which is", "site which is also", "which is also found in", "is also found in the", "also found in the control", "found in the control regions", "in the control regions of", "the control regions of numerous", "control regions of numerous muscle", "regions of numerous muscle specific", "of numerous muscle specific genes.", "numerous muscle specific genes. mef2", "muscle specific genes. mef2 and", "specific genes. mef2 and myogenic", "genes. mef2 and myogenic bhlh", "mef2 and myogenic bhlh proteins", "and myogenic bhlh proteins synergistically", "myogenic bhlh proteins synergistically activate", "bhlh proteins synergistically activate expression", "proteins synergistically activate expression of", "synergistically activate expression of muscle", "activate expression of muscle specific", "expression of muscle specific genes", "of muscle specific genes via", "muscle specific genes via protein", "specific genes via protein protein", "genes via protein protein interactions", "via protein protein interactions between", "protein protein interactions between dna", "protein interactions between dna binding", "interactions between dna binding domains", "between dna binding domains of", "dna binding domains of these", "binding domains of these heterologous", "domains of these heterologous classes", "of these heterologous classes of", "these heterologous classes of transcription", "heterologous classes of transcription factors.", "classes of transcription factors. members", "of transcription factors. members of", "transcription factors. members of the", "factors. members of the myod", "members of the myod and", "of the myod and mef2", "the myod and mef2 family", "myod and mef2 family of", "and mef2 family of transcription", "mef2 family of transcription factors", "family of transcription factors associate", "of transcription factors associate combinatorially", "transcription factors associate combinatorially to", "factors associate combinatorially to control", "associate combinatorially to control myoblast", "combinatorially to control myoblast specification", "control myoblast specification differentiation", "myoblast specification differentiation and", "specification differentiation and proliferation." ] }, { "record_id": "GLY_000594_1_414", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5339716", "r hsa", "hsa 5339716", "r hsa 5339716" ] }, { "record_id": "GLY_000594_1_414", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by gsk3beta", "gsk3beta mutants", "signaling by gsk3beta", "by gsk3beta mutants", "signaling by gsk3beta mutants", "gsk3beta is", "is subject", "subject to", "to in", "in frame", "frame missplicing", "missplicing in", "in cml", "cml stem", "stem cells", "cells resulting", "resulting in", "in the", "the production", "production of", "of mutant", "mutant protein", "protein that", "that lacks", "lacks the", "the axin", "axin and", "and frat", "frat binding", "binding domains.", "cells containing", "containing this", "this mutant", "mutant gsk3beta", "gsk3beta show", "show elevated", "elevated levels", "levels of", "of nuclear", "nuclear beta", "beta catenin", "catenin and", "and enhanced", "enhanced tcf", "tcf dependent", "dependent reporter", "reporter activity", "jamieson et", "et al", "abrahamsson et", "2009 .", "gsk3beta is subject", "is subject to", "subject to in", "to in frame", "in frame missplicing", "frame missplicing in", "missplicing in cml", "in cml stem", "cml stem cells", "stem cells resulting", "cells resulting in", "resulting in the", "in the production", "the production of", "production of mutant", "of mutant protein", "mutant protein that", "protein that lacks", "that lacks the", "lacks the axin", "the axin and", "axin and frat", "and frat binding", "frat binding domains.", "domains. cells", "cells containing this", "containing this mutant", "this mutant gsk3beta", "mutant gsk3beta show", "gsk3beta show elevated", "show elevated levels", "elevated levels of", "levels of nuclear", "of nuclear beta", "nuclear beta catenin", "beta catenin and", "catenin and enhanced", "and enhanced tcf", "enhanced tcf dependent", "tcf dependent reporter", "dependent reporter activity", "activity jamieson", "jamieson et al", "al 2008", "2008 abrahamsson", "abrahamsson et al", "al 2009", "gsk3beta is subject to", "is subject to in", "subject to in frame", "to in frame missplicing", "in frame missplicing in", "frame missplicing in cml", "missplicing in cml stem", "in cml stem cells", "cml stem cells resulting", "stem cells resulting in", "cells resulting in the", "resulting in the production", "in the production of", "the production of mutant", "production of mutant protein", "of mutant protein that", "mutant protein that lacks", "protein that lacks the", "that lacks the axin", "lacks the axin and", "the axin and frat", "axin and frat binding", "and frat binding domains.", "binding domains. cells", "domains. cells containing", "cells containing this mutant", "containing this mutant gsk3beta", "this mutant gsk3beta show", "mutant gsk3beta show elevated", "gsk3beta show elevated levels", "show elevated levels of", "elevated levels of nuclear", "levels of nuclear beta", "of nuclear beta catenin", "nuclear beta catenin and", "beta catenin and enhanced", "catenin and enhanced tcf", "and enhanced tcf dependent", "enhanced tcf dependent reporter", "tcf dependent reporter activity", "reporter activity jamieson", "activity jamieson et", "et al 2008", "2008 abrahamsson et", "et al 2009", "al 2009 .", "gsk3beta is subject to in", "is subject to in frame", "subject to in frame missplicing", "to in frame missplicing in", "in frame missplicing in cml", "frame missplicing in cml stem", "missplicing in cml stem cells", "in cml stem cells resulting", "cml stem cells resulting in", "stem cells resulting in the", "cells resulting in the production", "resulting in the production of", "in the production of mutant", "the production of mutant protein", "production of mutant protein that", "of mutant protein that lacks", "mutant protein that lacks the", "protein that lacks the axin", "that lacks the axin and", "lacks the axin and frat", "the axin and frat binding", "axin and frat binding domains.", "frat binding domains. cells", "binding domains. cells containing", "domains. cells containing this", "cells containing this mutant gsk3beta", "containing this mutant gsk3beta show", "this mutant gsk3beta show elevated", "mutant gsk3beta show elevated levels", "gsk3beta show elevated levels of", "show elevated levels of nuclear", "elevated levels of nuclear beta", "levels of nuclear beta catenin", "of nuclear beta catenin and", "nuclear beta catenin and enhanced", "beta catenin and enhanced tcf", "catenin and enhanced tcf dependent", "and enhanced tcf dependent reporter", "enhanced tcf dependent reporter activity", "dependent reporter activity jamieson", "reporter activity jamieson et", "activity jamieson et al", "jamieson et al 2008", "al 2008 abrahamsson", "2008 abrahamsson et al", "abrahamsson et al 2009", "et al 2009 ." ] }, { "record_id": "GLY_000594_1_415", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5357905", "r hsa", "hsa 5357905", "r hsa 5357905" ] }, { "record_id": "GLY_000594_1_415", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of tnfr1", "tnfr1 signaling", "regulation of tnfr1", "of tnfr1 signaling", "regulation of tnfr1 signaling", "tumor necrosis", "necrosis factor", "factor alpha", "is an", "an inflammatory", "inflammatory cytokine", "that activates", "activates either", "either cell", "cell survival", "e.g. inflammation", "or cell", "cell death", "death upon", "upon association", "association with", "with tnf", "tnf receptor", "receptor 1", "tnfr1 .", ". stimuli", "stimuli and", "and the", "the cellular", "cellular context", "context dictate", "dictate cell", "cell fate", "fate decisions", "decisions between", "between survival", "survival and", "and death", "death which", "which rely", "rely on", "on tightly", "tightly regulated", "regulated mechanisms", "mechanisms with", "with checkpoints", "checkpoints on", "on many", "many levels.", "levels. the", "the tnfr1", "signaling is", "is controlled", "controlled by", "by the", "the interplay", "interplay between", "between post", "post translational", "translational modifications", "modifications such", "such as", "as proteolytic", "proteolytic processing", "processing by", "by active", "active caspases", "caspases or", "or ubiquitination/deubiquitination", "ubiquitination/deubiquitination by", "by lubac", "lubac or", "or cyld", "cyld ubiquitin", "ubiquitin editing", "editing complexes.", "complexes. tnfr1", "tnfr1 mediated", "mediated nfkappab", "nfkappab activation", "activation leads", "leads to", "to the", "the pro", "pro survival", "survival transcriptional", "transcriptional program", "program that", "that is", "is both", "both anti", "anti apoptotic", "apoptotic and", "and highly", "highly proinflammatory.", "proinflammatory. the", "the constitutive", "constitutive nfkappab", "nfkappab or", "or ap1", "ap1 activation", "activation may", "may lead", "lead to", "to excessive", "excessive inflammation", "inflammation which", "which has", "has been", "been associated", "associated with", "with a", "a variety", "variety of", "of aggressive", "aggressive tumor", "tumor types", "jackson bernitsas", "bernitsas dg", "dg et", "et al.", "al. 2007", "zhang jy", "jy et", "2007 .", ". thus", "the tight", "tight regulation", "of tnf\u03b1:tnfr1", "tnf\u03b1:tnfr1 signaling", "is required", "required to", "to ensure", "ensure the", "the appropriate", "appropriate cell", "cell response", "response to", "to stimuli.", "tumor necrosis factor", "necrosis factor alpha", "alpha tnf\u03b1", "tnf\u03b1 is", "is an inflammatory", "an inflammatory cytokine", "cytokine that", "that activates either", "activates either cell", "either cell survival", "survival e.g.", "inflammation proliferation", "proliferation or", "or cell death", "cell death upon", "death upon association", "upon association with", "association with tnf", "with tnf receptor", "tnf receptor 1", "1 tnfr1", "tnfr1 . stimuli", ". stimuli and", "stimuli and the", "and the cellular", "the cellular context", "cellular context dictate", "context dictate cell", "dictate cell fate", "cell fate decisions", "fate decisions between", "decisions between survival", "between survival and", "survival and death", "and death which", "death which rely", "which rely on", "rely on tightly", "on tightly regulated", "tightly regulated mechanisms", "regulated mechanisms with", "mechanisms with checkpoints", "with checkpoints on", "checkpoints on many", "on many levels.", "many levels. the", "levels. the tnfr1", "the tnfr1 signaling", "tnfr1 signaling is", "signaling is controlled", "is controlled by", "controlled by the", "by the interplay", "the interplay between", "interplay between post", "between post translational", "post translational modifications", "translational modifications such", "modifications such as", "such as proteolytic", "as proteolytic processing", "proteolytic processing by", "processing by active", "by active caspases", "active caspases or", "caspases or ubiquitination/deubiquitination", "or ubiquitination/deubiquitination by", "ubiquitination/deubiquitination by lubac", "by lubac or", "lubac or cyld", "or cyld ubiquitin", "cyld ubiquitin editing", "ubiquitin editing complexes.", "editing complexes. tnfr1", "complexes. tnfr1 mediated", "tnfr1 mediated nfkappab", "mediated nfkappab activation", "nfkappab activation leads", "activation leads to", "leads to the", "to the pro", "the pro survival", "pro survival transcriptional", "survival transcriptional program", "transcriptional program that", "program that is", "that is both", "is both anti", "both anti apoptotic", "anti apoptotic and", "apoptotic and highly", "and highly proinflammatory.", "highly proinflammatory. the", "proinflammatory. the constitutive", "the constitutive nfkappab", "constitutive nfkappab or", "nfkappab or ap1", "or ap1 activation", "ap1 activation may", "activation may lead", "may lead to", "lead to excessive", "to excessive inflammation", "excessive inflammation which", "inflammation which has", "which has been", "has been associated", "been associated with", "associated with a", "with a variety", "a variety of", "variety of aggressive", "of aggressive tumor", "aggressive tumor types", "types jackson", "jackson bernitsas dg", "bernitsas dg et", "dg et al.", "et al. 2007", "2007 zhang", "zhang jy et", "jy et al.", "al. 2007 .", "2007 . thus", "thus the", "the tight regulation", "tight regulation of", "regulation of tnf\u03b1:tnfr1", "of tnf\u03b1:tnfr1 signaling", "tnf\u03b1:tnfr1 signaling is", "signaling is required", "is required to", "required to ensure", "to ensure the", "ensure the appropriate", "the appropriate cell", "appropriate cell response", "cell response to", "response to stimuli.", "tumor necrosis factor alpha", "factor alpha tnf\u03b1", "tnf\u03b1 is an", "is an inflammatory cytokine", "inflammatory cytokine that", "cytokine that activates", "that activates either cell", "activates either cell survival", "cell survival e.g.", "survival e.g. inflammation", "e.g. inflammation proliferation", "proliferation or cell", "or cell death upon", "cell death upon association", "death upon association with", "upon association with tnf", "association with tnf receptor", "with tnf receptor 1", "receptor 1 tnfr1", "1 tnfr1 .", "tnfr1 . stimuli and", ". stimuli and the", "stimuli and the cellular", "and the cellular context", "the cellular context dictate", "cellular context dictate cell", "context dictate cell fate", "dictate cell fate decisions", "cell fate decisions between", "fate decisions between survival", "decisions between survival and", "between survival and death", "survival and death which", "and death which rely", "death which rely on", "which rely on tightly", "rely on tightly regulated", "on tightly regulated mechanisms", "tightly regulated mechanisms with", "regulated mechanisms with checkpoints", "mechanisms with checkpoints on", "with checkpoints on many", "checkpoints on many levels.", "on many levels. the", "many levels. the tnfr1", "levels. the tnfr1 signaling", "the tnfr1 signaling is", "tnfr1 signaling is controlled", "signaling is controlled by", "is controlled by the", "controlled by the interplay", "by the interplay between", "the interplay between post", "interplay between post translational", "between post translational modifications", "post translational modifications such", "translational modifications such as", "modifications such as proteolytic", "such as proteolytic processing", "as proteolytic processing by", "proteolytic processing by active", "processing by active caspases", "by active caspases or", "active caspases or ubiquitination/deubiquitination", "caspases or ubiquitination/deubiquitination by", "or ubiquitination/deubiquitination by lubac", "ubiquitination/deubiquitination by lubac or", "by lubac or cyld", "lubac or cyld ubiquitin", "or cyld ubiquitin editing", "cyld ubiquitin editing complexes.", "ubiquitin editing complexes. tnfr1", "editing complexes. tnfr1 mediated", "complexes. tnfr1 mediated nfkappab", "tnfr1 mediated nfkappab activation", "mediated nfkappab activation leads", "nfkappab activation leads to", "activation leads to the", "leads to the pro", "to the pro survival", "the pro survival transcriptional", "pro survival transcriptional program", "survival transcriptional program that", "transcriptional program that is", "program that is both", "that is both anti", "is both anti apoptotic", "both anti apoptotic and", "anti apoptotic and highly", "apoptotic and highly proinflammatory.", "and highly proinflammatory. the", "highly proinflammatory. the constitutive", "proinflammatory. the constitutive nfkappab", "the constitutive nfkappab or", "constitutive nfkappab or ap1", "nfkappab or ap1 activation", "or ap1 activation may", "ap1 activation may lead", "activation may lead to", "may lead to excessive", "lead to excessive inflammation", "to excessive inflammation which", "excessive inflammation which has", "inflammation which has been", "which has been associated", "has been associated with", "been associated with a", "associated with a variety", "with a variety of", "a variety of aggressive", "variety of aggressive tumor", "of aggressive tumor types", "tumor types jackson", "types jackson bernitsas", "jackson bernitsas dg et", "bernitsas dg et al.", "dg et al. 2007", "al. 2007 zhang", "2007 zhang jy", "zhang jy et al.", "jy et al. 2007", "et al. 2007 .", "al. 2007 . thus", ". thus the", "thus the tight", "the tight regulation of", "tight regulation of tnf\u03b1:tnfr1", "regulation of tnf\u03b1:tnfr1 signaling", "of tnf\u03b1:tnfr1 signaling is", "tnf\u03b1:tnfr1 signaling is required", "signaling is required to", "is required to ensure", "required to ensure the", "to ensure the appropriate", "ensure the appropriate cell", "the appropriate cell response", "appropriate cell response to", "cell response to stimuli.", "necrosis factor alpha tnf\u03b1", "alpha tnf\u03b1 is", "tnf\u03b1 is an inflammatory", "an inflammatory cytokine that", "inflammatory cytokine that activates", "cytokine that activates either", "that activates either cell survival", "either cell survival e.g.", "cell survival e.g. inflammation", "inflammation proliferation or", "proliferation or cell death", "or cell death upon association", "cell death upon association with", "death upon association with tnf", "upon association with tnf receptor", "association with tnf receptor 1", "tnf receptor 1 tnfr1", "receptor 1 tnfr1 .", "1 tnfr1 . stimuli", "tnfr1 . stimuli and the", ". stimuli and the cellular", "stimuli and the cellular context", "and the cellular context dictate", "the cellular context dictate cell", "cellular context dictate cell fate", "context dictate cell fate decisions", "dictate cell fate decisions between", "cell fate decisions between survival", "fate decisions between survival and", "decisions between survival and death", "between survival and death which", "survival and death which rely", "and death which rely on", "death which rely on tightly", "which rely on tightly regulated", "rely on tightly regulated mechanisms", "on tightly regulated mechanisms with", "tightly regulated mechanisms with checkpoints", "regulated mechanisms with checkpoints on", "mechanisms with checkpoints on many", "with checkpoints on many levels.", "checkpoints on many levels. the", "on many levels. the tnfr1", "many levels. the tnfr1 signaling", "levels. the tnfr1 signaling is", "the tnfr1 signaling is controlled", "tnfr1 signaling is controlled by", "signaling is controlled by the", "is controlled by the interplay", "controlled by the interplay between", "by the interplay between post", "the interplay between post translational", "interplay between post translational modifications", "between post translational modifications such", "post translational modifications such as", "translational modifications such as proteolytic", "modifications such as proteolytic processing", "such as proteolytic processing by", "as proteolytic processing by active", "proteolytic processing by active caspases", "processing by active caspases or", "by active caspases or ubiquitination/deubiquitination", "active caspases or ubiquitination/deubiquitination by", "caspases or ubiquitination/deubiquitination by lubac", "or ubiquitination/deubiquitination by lubac or", "ubiquitination/deubiquitination by lubac or cyld", "by lubac or cyld ubiquitin", "lubac or cyld ubiquitin editing", "or cyld ubiquitin editing complexes.", "cyld ubiquitin editing complexes. tnfr1", "ubiquitin editing complexes. tnfr1 mediated", "editing complexes. tnfr1 mediated nfkappab", "complexes. tnfr1 mediated nfkappab activation", "tnfr1 mediated nfkappab activation leads", "mediated nfkappab activation leads to", "nfkappab activation leads to the", "activation leads to the pro", "leads to the pro survival", "to the pro survival transcriptional", "the pro survival transcriptional program", "pro survival transcriptional program that", "survival transcriptional program that is", "transcriptional program that is both", "program that is both anti", "that is both anti apoptotic", "is both anti apoptotic and", "both anti apoptotic and highly", "anti apoptotic and highly proinflammatory.", "apoptotic and highly proinflammatory. the", "and highly proinflammatory. the constitutive", "highly proinflammatory. the constitutive nfkappab", "proinflammatory. the constitutive nfkappab or", "the constitutive nfkappab or ap1", "constitutive nfkappab or ap1 activation", "nfkappab or ap1 activation may", "or ap1 activation may lead", "ap1 activation may lead to", "activation may lead to excessive", "may lead to excessive inflammation", "lead to excessive inflammation which", "to excessive inflammation which has", "excessive inflammation which has been", "inflammation which has been associated", "which has been associated with", "has been associated with a", "been associated with a variety", "associated with a variety of", "with a variety of aggressive", "a variety of aggressive tumor", "variety of aggressive tumor types", "aggressive tumor types jackson", "tumor types jackson bernitsas", "types jackson bernitsas dg", "jackson bernitsas dg et al.", "bernitsas dg et al. 2007", "et al. 2007 zhang", "al. 2007 zhang jy", "2007 zhang jy et", "zhang jy et al. 2007", "jy et al. 2007 .", "et al. 2007 . thus", "2007 . thus the", ". thus the tight", "thus the tight regulation", "the tight regulation of tnf\u03b1:tnfr1", "tight regulation of tnf\u03b1:tnfr1 signaling", "regulation of tnf\u03b1:tnfr1 signaling is", "of tnf\u03b1:tnfr1 signaling is required", "tnf\u03b1:tnfr1 signaling is required to", "signaling is required to ensure", "is required to ensure the", "required to ensure the appropriate", "to ensure the appropriate cell", "ensure the appropriate cell response", "the appropriate cell response to", "appropriate cell response to stimuli." ] }, { "record_id": "GLY_000594_1_416", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5357956", "r hsa", "hsa 5357956", "r hsa 5357956" ] }, { "record_id": "GLY_000594_1_416", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tnfr1 induced", "induced nf", "nf kappa", "kappa b", "b signaling", "signaling pathway", "tnfr1 induced nf", "induced nf kappa", "nf kappa b", "kappa b signaling", "b signaling pathway", "tnfr1 induced nf kappa", "induced nf kappa b", "nf kappa b signaling", "kappa b signaling pathway", "tnfr1 induced nf kappa b", "induced nf kappa b signaling", "nf kappa b signaling pathway", "activation of", "of tumor", "tumor necrosis", "necrosis factor", "factor receptor", "receptor 1", "can trigger", "trigger multiple", "multiple signal", "signal transduction", "transduction pathways", "pathways to", "to induce", "induce inflammation", "cell proliferation", "survival or", "or cell", "cell death", "ward c", "c et", "et al.", "al. 1999", "micheau o", "o and", "and tschopp", "tschopp j", "j 2003", "widera d", "d et", "al. 2006", "2006 .", ". whether", "whether a", "a tnf", "tnf \u03b1", "\u03b1 stimulated", "stimulated cell", "cell will", "will survive", "survive or", "or die", "die is", "is dependent", "dependent on", "on the", "the cellular", "cellular context.", "context. tnf", "\u03b1 induced", "induced signals", "signals lead", "lead to", "to the", "the activation", "of transcriptional", "transcriptional factors", "factors such", "such as", "as nuclear", "nuclear factor", "factor kappa", "and activator", "activator protein", "protein 1", "tsou hk", "hk et", "al. 2012", "2012 .

", ".

the", "the binding", "binding of", "of tnf", "\u03b1 to", "to tnfr1", "tnfr1 leads", "leads to", "to recruitment", "recruitment of", "of the", "the adapter", "adapter protein", "protein tnfr1", "tnfr1 associated", "associated death", "death domain", "and of", "of receptor\u2011interacting", "receptor\u2011interacting protein", "ripk1 .", ". tradd", "tradd subsequently", "subsequently recruits", "recruits also", "also tnf", "tnf receptor", "receptor associated", "associated factor", "factor 2", "traf2 .", ". ripk1", "ripk1 is", "is promptly", "promptly k63", "k63 polyubiquitinated", "polyubiquitinated which", "which results", "results in", "in the", "the recruitment", "the tab2:tak1", "tab2:tak1 complex", "complex and", "and the", "the ikb", "ikb kinase", "complex to", "to tnfr1.", "tnfr1. the", "the activated", "activated ikk", "ikk complex", "complex mediates", "mediates phosphorylation", "phosphorylation of", "the inhibitor", "inhibitor of", "of nfkappab", "which targets", "targets ikb", "ikb for", "for ubiquitination", "ubiquitination and", "and subsequent", "subsequent degradation.", "degradation. released", "released nfkappab", "nfkappab induces", "induces the", "the expression", "expression of", "of a", "a variety", "variety of", "of genes", "genes including", "including inflammation", "inflammation related", "related genes", "genes and", "and anti", "anti apoptotic", "apoptotic genes", "genes encoding", "encoding proteins", "proteins such", "as inhibitor", "of apoptosis", "apoptosis proteins", "proteins ciap1/2", "bcl 2", "bcl xl", "xl or", "or cellular", "cellular flice", "flice like", "like inhibitory", "inhibitory protein", "blonska m", "m et", "al. 2005", "ea ck", "ck et", "wu cj", "cj et", "chen c", "al. 2000", "manna sk", "sk et", "kreuz s", "s et", "al. 2001", "o et", "2001 .", ". nfkb", "nfkb mediated", "mediated inhibition", "inhibition of", "of cell", "death also", "also involves", "involves attenuating", "attenuating tnf", "tnf induced", "induced activation", "of c", "c jun", "jun activating", "activating kinase", "jnk .", ". whereas", "whereas transient", "transient activation", "of jnk", "jnk upon", "upon tnf", "tnf treatment", "treatment is", "is associated", "associated with", "with cellular", "cellular survival", "prolonged jnk", "jnk activation", "activation contributes", "contributes to", "to cell", "cell death.", "death. however", "as caspases", "caspases activate", "activate jnk", "jnk quite", "quite efficiently", "jnks are", "are also", "also regularly", "regularly stimulated", "stimulated in", "in course", "course of", "apoptosis without", "without being", "being essential", "essential for", "for cell", "wicovsky a", "a et", "al. 2007", "2007 .", ". ap1", "ap1 mediated", "mediated gene", "gene induction", "induction results", "results from", "from activation", "jnk via", "via traf2", "not shown", "shown here", "2012 .", ". while", "while pro", "pro survival", "survival signaling", "signaling is", "is initiated", "initiated and", "and regulated", "regulated via", "via the", "activated tnfr1", "tnfr1 receptor", "receptor complex", "complex at", "at the", "the cell", "cell membrane", "death signals", "signals are", "are induced", "induced by", "by internalization", "internalization associated", "associated fashion", "fashion upon", "upon the", "the release", "release of", "of ripk1", "ripk1 from", "from the", "the membrane", "membrane complex", "schneider brachert", "brachert w", "w et", "al. 2004", "tchikov v", "v et", "al. 2011", "2011 .

tnfr1", ".

tnfr1 mediated", "mediated transcriptional", "transcriptional activity", "activity of", "of nfkb", "nfkb is", "is both", "both antiapoptotic", "antiapoptotic and", "and highly", "highly proinflammatory", "proinflammatory and", "and thus", "thus must", "must be", "be tightly", "tightly regulated", "regulated to", "to prevent", "prevent constitutive", "constitutive activation", "activation that", "that leads", "to persistent", "persistent inflammation", "inflammation and", "and cancer", "fujihara s", "al. 2002", "pekalski j", "j et", "al. 2013", "kankaanranta h", "h et", "al. 2014", "shukla s", "s and", "and gupta", "gupta s", "s 2004", "jackson bernitsas", "bernitsas dg", "dg et", "zhang jy", "jy et", ". multiple", "multiple mechanisms", "mechanisms normally", "normally ensure", "ensure the", "the proper", "proper control", "control of", "nfkappab activation", "activation including", "including two", "two negative", "negative feedback", "feedback loops", "loops mediated", "mediated by", "by nfkappab", "nfkappab inducible", "inducible inhibitors", "ikb alpha", "and ubiquitin", "ubiquitin editing", "editing protein", "protein a20", "he kl", "kl &", "& ting", "ting at", "at 2002", "wertz ie", "ie et", "vereecke l", "l et", "al. 2009", "2013 .", "activation of tumor", "of tumor necrosis", "tumor necrosis factor", "necrosis factor receptor", "factor receptor 1", "1 tnfr1", "tnfr1 can", "can trigger multiple", "trigger multiple signal", "multiple signal transduction", "signal transduction pathways", "transduction pathways to", "pathways to induce", "to induce inflammation", "inflammation cell", "proliferation survival", "survival or cell", "or cell death", "death ward", "ward c et", "c et al.", "et al. 1999", "1999 micheau", "micheau o and", "o and tschopp", "and tschopp j", "tschopp j 2003", "2003 widera", "widera d et", "d et al.", "et al. 2006", "al. 2006 .", "2006 . whether", ". whether a", "whether a tnf", "a tnf \u03b1", "tnf \u03b1 stimulated", "\u03b1 stimulated cell", "stimulated cell will", "cell will survive", "will survive or", "survive or die", "or die is", "die is dependent", "is dependent on", "dependent on the", "on the cellular", "the cellular context.", "cellular context. tnf", "context. tnf \u03b1", "tnf \u03b1 induced", "\u03b1 induced signals", "induced signals lead", "signals lead to", "lead to the", "to the activation", "the activation of", "activation of transcriptional", "of transcriptional factors", "transcriptional factors such", "factors such as", "such as nuclear", "as nuclear factor", "nuclear factor kappa", "factor kappa b", "b nfkappab", "nfkappab and", "and activator protein", "activator protein 1", "1 ap1", "1999 widera", "2006 tsou", "tsou hk et", "hk et al.", "et al. 2012", "al. 2012 .

", "2012 .

the", ".

the binding", "the binding of", "binding of tnf", "of tnf \u03b1", "tnf \u03b1 to", "\u03b1 to tnfr1", "to tnfr1 leads", "tnfr1 leads to", "leads to recruitment", "to recruitment of", "recruitment of the", "of the adapter", "the adapter protein", "adapter protein tnfr1", "protein tnfr1 associated", "tnfr1 associated death", "associated death domain", "domain tradd", "tradd and", "and of receptor\u2011interacting", "of receptor\u2011interacting protein", "receptor\u2011interacting protein 1", "1 ripk1", "ripk1 . tradd", ". tradd subsequently", "tradd subsequently recruits", "subsequently recruits also", "recruits also tnf", "also tnf receptor", "tnf receptor associated", "receptor associated factor", "associated factor 2", "2 traf2", "traf2 . ripk1", ". ripk1 is", "ripk1 is promptly", "is promptly k63", "promptly k63 polyubiquitinated", "k63 polyubiquitinated which", "polyubiquitinated which results", "which results in", "results in the", "in the recruitment", "the recruitment of", "of the tab2:tak1", "the tab2:tak1 complex", "tab2:tak1 complex and", "complex and the", "and the ikb", "the ikb kinase", "kinase ikk", "complex to tnfr1.", "to tnfr1. the", "tnfr1. the activated", "the activated ikk", "activated ikk complex", "ikk complex mediates", "complex mediates phosphorylation", "mediates phosphorylation of", "phosphorylation of the", "of the inhibitor", "the inhibitor of", "inhibitor of nfkappab", "nfkappab ikb", "which targets ikb", "targets ikb for", "ikb for ubiquitination", "for ubiquitination and", "ubiquitination and subsequent", "and subsequent degradation.", "subsequent degradation. released", "degradation. released nfkappab", "released nfkappab induces", "nfkappab induces the", "induces the expression", "the expression of", "expression of a", "of a variety", "a variety of", "variety of genes", "of genes including", "genes including inflammation", "including inflammation related", "inflammation related genes", "related genes and", "genes and anti", "and anti apoptotic", "anti apoptotic genes", "apoptotic genes encoding", "genes encoding proteins", "encoding proteins such", "proteins such as", "such as inhibitor", "as inhibitor of", "inhibitor of apoptosis", "of apoptosis proteins", "apoptosis proteins ciap1/2", "ciap1/2 bcl", "2 bcl", "bcl xl or", "xl or cellular", "or cellular flice", "cellular flice like", "flice like inhibitory", "like inhibitory protein", "protein flip", "blonska m et", "m et al.", "et al. 2005", "2005 ea", "ea ck et", "ck et al.", "2006 wu", "wu cj et", "cj et al.", "2006 chen", "chen c et", "et al. 2000", "2000 manna", "manna sk et", "sk et al.", "2000 kreuz", "kreuz s et", "s et al.", "et al. 2001", "2001 micheau", "micheau o et", "o et al.", "al. 2001 .", "2001 . nfkb", ". nfkb mediated", "nfkb mediated inhibition", "mediated inhibition of", "inhibition of cell", "of cell death", "cell death also", "death also involves", "also involves attenuating", "involves attenuating tnf", "attenuating tnf induced", "tnf induced activation", "induced activation of", "activation of c", "of c jun", "c jun activating", "jun activating kinase", "kinase jnk", "jnk . whereas", ". whereas transient", "whereas transient activation", "transient activation of", "activation of jnk", "of jnk upon", "jnk upon tnf", "upon tnf treatment", "tnf treatment is", "treatment is associated", "is associated with", "associated with cellular", "with cellular survival", "survival prolonged", "prolonged jnk activation", "jnk activation contributes", "activation contributes to", "contributes to cell", "to cell death.", "cell death. however", "however as", "as caspases activate", "caspases activate jnk", "activate jnk quite", "jnk quite efficiently", "efficiently jnks", "jnks are also", "are also regularly", "also regularly stimulated", "regularly stimulated in", "stimulated in course", "in course of", "course of apoptosis", "of apoptosis without", "apoptosis without being", "without being essential", "being essential for", "essential for cell", "for cell death", "death wicovsky", "wicovsky a et", "a et al.", "et al. 2007", "al. 2007 .", "2007 . ap1", ". ap1 mediated", "ap1 mediated gene", "mediated gene induction", "gene induction results", "induction results from", "results from activation", "from activation of", "of jnk via", "jnk via traf2", "traf2 not", "not shown here", "al. 2012 .", "2012 . while", ". while pro", "while pro survival", "pro survival signaling", "survival signaling is", "signaling is initiated", "is initiated and", "initiated and regulated", "and regulated via", "regulated via the", "via the activated", "the activated tnfr1", "activated tnfr1 receptor", "tnfr1 receptor complex", "receptor complex at", "complex at the", "at the cell", "the cell membrane", "membrane cell", "cell death signals", "death signals are", "signals are induced", "are induced by", "induced by internalization", "by internalization associated", "internalization associated fashion", "associated fashion upon", "fashion upon the", "upon the release", "the release of", "release of ripk1", "of ripk1 from", "ripk1 from the", "from the membrane", "the membrane complex", "complex micheau", "2003 schneider", "schneider brachert w", "brachert w et", "w et al.", "et al. 2004", "2004 tchikov", "tchikov v et", "v et al.", "et al. 2011", "al. 2011 .

tnfr1", "2011 .

tnfr1 mediated", ".

tnfr1 mediated transcriptional", "mediated transcriptional activity", "transcriptional activity of", "activity of nfkb", "of nfkb is", "nfkb is both", "is both antiapoptotic", "both antiapoptotic and", "antiapoptotic and highly", "and highly proinflammatory", "highly proinflammatory and", "proinflammatory and thus", "and thus must", "thus must be", "must be tightly", "be tightly regulated", "tightly regulated to", "regulated to prevent", "to prevent constitutive", "prevent constitutive activation", "constitutive activation that", "activation that leads", "that leads to", "leads to persistent", "to persistent inflammation", "persistent inflammation and", "inflammation and cancer", "cancer ward", "1999 fujihara", "fujihara s et", "et al. 2002", "2002 pekalski", "pekalski j et", "j et al.", "et al. 2013", "2013 kankaanranta", "kankaanranta h et", "h et al.", "et al. 2014", "2014 shukla", "shukla s and", "s and gupta", "and gupta s", "gupta s 2004", "2004 jackson", "jackson bernitsas dg", "bernitsas dg et", "dg et al.", "2007 zhang", "zhang jy et", "jy et al.", "2007 . multiple", ". multiple mechanisms", "multiple mechanisms normally", "mechanisms normally ensure", "normally ensure the", "ensure the proper", "the proper control", "proper control of", "control of nfkappab", "of nfkappab activation", "nfkappab activation including", "activation including two", "including two negative", "two negative feedback", "negative feedback loops", "feedback loops mediated", "loops mediated by", "mediated by nfkappab", "by nfkappab inducible", "nfkappab inducible inhibitors", "inhibitors ikb", "alpha nfkbia", "nfkbia and", "and ubiquitin editing", "ubiquitin editing protein", "editing protein a20", "a20 he", "he kl &", "kl & ting", "& ting at", "ting at 2002", "2002 wertz", "wertz ie et", "ie et al.", "2004 vereecke", "vereecke l et", "l et al.", "et al. 2009", "2009 pekalski", "al. 2013 .", "activation of tumor necrosis", "of tumor necrosis factor", "tumor necrosis factor receptor", "necrosis factor receptor 1", "receptor 1 tnfr1", "tnfr1 can trigger", "can trigger multiple signal", "trigger multiple signal transduction", "multiple signal transduction pathways", "signal transduction pathways to", "transduction pathways to induce", "pathways to induce inflammation", "induce inflammation cell", "inflammation cell proliferation", "cell proliferation survival", "proliferation survival or", "survival or cell death", "cell death ward", "death ward c", "ward c et al.", "c et al. 1999", "al. 1999 micheau", "1999 micheau o", "micheau o and tschopp", "o and tschopp j", "and tschopp j 2003", "j 2003 widera", "2003 widera d", "widera d et al.", "d et al. 2006", "et al. 2006 .", "al. 2006 . whether", "2006 . whether a", ". whether a tnf", "whether a tnf \u03b1", "a tnf \u03b1 stimulated", "tnf \u03b1 stimulated cell", "\u03b1 stimulated cell will", "stimulated cell will survive", "cell will survive or", "will survive or die", "survive or die is", "or die is dependent", "die is dependent on", "is dependent on the", "dependent on the cellular", "on the cellular context.", "the cellular context. tnf", "cellular context. tnf \u03b1", "context. tnf \u03b1 induced", "tnf \u03b1 induced signals", "\u03b1 induced signals lead", "induced signals lead to", "signals lead to the", "lead to the activation", "to the activation of", "the activation of transcriptional", "activation of transcriptional factors", "of transcriptional factors such", "transcriptional factors such as", "factors such as nuclear", "such as nuclear factor", "as nuclear factor kappa", "nuclear factor kappa b", "kappa b nfkappab", "nfkappab and activator", "and activator protein 1", "protein 1 ap1", "ap1 ward", "al. 1999 widera", "1999 widera d", "al. 2006 tsou", "2006 tsou hk", "tsou hk et al.", "hk et al. 2012", "et al. 2012 .

", "al. 2012 .

the", "2012 .

the binding", ".

the binding of", "the binding of tnf", "binding of tnf \u03b1", "of tnf \u03b1 to", "tnf \u03b1 to tnfr1", "\u03b1 to tnfr1 leads", "to tnfr1 leads to", "tnfr1 leads to recruitment", "leads to recruitment of", "to recruitment of the", "recruitment of the adapter", "of the adapter protein", "the adapter protein tnfr1", "adapter protein tnfr1 associated", "protein tnfr1 associated death", "tnfr1 associated death domain", "death domain tradd", "tradd and of", "and of receptor\u2011interacting protein", "of receptor\u2011interacting protein 1", "protein 1 ripk1", "1 ripk1 .", "ripk1 . tradd subsequently", ". tradd subsequently recruits", "tradd subsequently recruits also", "subsequently recruits also tnf", "recruits also tnf receptor", "also tnf receptor associated", "tnf receptor associated factor", "receptor associated factor 2", "factor 2 traf2", "2 traf2 .", "traf2 . ripk1 is", ". ripk1 is promptly", "ripk1 is promptly k63", "is promptly k63 polyubiquitinated", "promptly k63 polyubiquitinated which", "k63 polyubiquitinated which results", "polyubiquitinated which results in", "which results in the", "results in the recruitment", "in the recruitment of", "the recruitment of the", "recruitment of the tab2:tak1", "of the tab2:tak1 complex", "the tab2:tak1 complex and", "tab2:tak1 complex and the", "complex and the ikb", "and the ikb kinase", "ikb kinase ikk", "ikk complex to", "complex to tnfr1. the", "to tnfr1. the activated", "tnfr1. the activated ikk", "the activated ikk complex", "activated ikk complex mediates", "ikk complex mediates phosphorylation", "complex mediates phosphorylation of", "mediates phosphorylation of the", "phosphorylation of the inhibitor", "of the inhibitor of", "the inhibitor of nfkappab", "of nfkappab ikb", "ikb which", "which targets ikb for", "targets ikb for ubiquitination", "ikb for ubiquitination and", "for ubiquitination and subsequent", "ubiquitination and subsequent degradation.", "and subsequent degradation. released", "subsequent degradation. released nfkappab", "degradation. released nfkappab induces", "released nfkappab induces the", "nfkappab induces the expression", "induces the expression of", "the expression of a", "expression of a variety", "of a variety of", "a variety of genes", "variety of genes including", "of genes including inflammation", "genes including inflammation related", "including inflammation related genes", "inflammation related genes and", "related genes and anti", "genes and anti apoptotic", "and anti apoptotic genes", "anti apoptotic genes encoding", "apoptotic genes encoding proteins", "genes encoding proteins such", "encoding proteins such as", "proteins such as inhibitor", "such as inhibitor of", "as inhibitor of apoptosis", "inhibitor of apoptosis proteins", "of apoptosis proteins ciap1/2", "proteins ciap1/2 bcl", "ciap1/2 bcl 2", "bcl 2 bcl", "2 bcl xl", "bcl xl or cellular", "xl or cellular flice", "or cellular flice like", "cellular flice like inhibitory", "flice like inhibitory protein", "inhibitory protein flip", "flip blonska", "blonska m et al.", "m et al. 2005", "al. 2005 ea", "2005 ea ck", "ea ck et al.", "ck et al. 2006", "al. 2006 wu", "2006 wu cj", "wu cj et al.", "cj et al. 2006", "al. 2006 chen", "2006 chen c", "chen c et al.", "c et al. 2000", "al. 2000 manna", "2000 manna sk", "manna sk et al.", "sk et al. 2000", "al. 2000 kreuz", "2000 kreuz s", "kreuz s et al.", "s et al. 2001", "al. 2001 micheau", "2001 micheau o", "micheau o et al.", "o et al. 2001", "et al. 2001 .", "al. 2001 . nfkb", "2001 . nfkb mediated", ". nfkb mediated inhibition", "nfkb mediated inhibition of", "mediated inhibition of cell", "inhibition of cell death", "of cell death also", "cell death also involves", "death also involves attenuating", "also involves attenuating tnf", "involves attenuating tnf induced", "attenuating tnf induced activation", "tnf induced activation of", "induced activation of c", "activation of c jun", "of c jun activating", "c jun activating kinase", "activating kinase jnk", "kinase jnk .", "jnk . whereas transient", ". whereas transient activation", "whereas transient activation of", "transient activation of jnk", "activation of jnk upon", "of jnk upon tnf", "jnk upon tnf treatment", "upon tnf treatment is", "tnf treatment is associated", "treatment is associated with", "is associated with cellular", "associated with cellular survival", "cellular survival prolonged", "survival prolonged jnk", "prolonged jnk activation contributes", "jnk activation contributes to", "activation contributes to cell", "contributes to cell death.", "to cell death. however", "death. however as", "however as caspases", "as caspases activate jnk", "caspases activate jnk quite", "activate jnk quite efficiently", "quite efficiently jnks", "efficiently jnks are", "jnks are also regularly", "are also regularly stimulated", "also regularly stimulated in", "regularly stimulated in course", "stimulated in course of", "in course of apoptosis", "course of apoptosis without", "of apoptosis without being", "apoptosis without being essential", "without being essential for", "being essential for cell", "essential for cell death", "cell death wicovsky", "death wicovsky a", "wicovsky a et al.", "a et al. 2007", "et al. 2007 .", "al. 2007 . ap1", "2007 . ap1 mediated", ". ap1 mediated gene", "ap1 mediated gene induction", "mediated gene induction results", "gene induction results from", "induction results from activation", "results from activation of", "from activation of jnk", "activation of jnk via", "of jnk via traf2", "via traf2 not", "traf2 not shown", "here tsou", "et al. 2012 .", "al. 2012 . while", "2012 . while pro", ". while pro survival", "while pro survival signaling", "pro survival signaling is", "survival signaling is initiated", "signaling is initiated and", "is initiated and regulated", "initiated and regulated via", "and regulated via the", "regulated via the activated", "via the activated tnfr1", "the activated tnfr1 receptor", "activated tnfr1 receptor complex", "tnfr1 receptor complex at", "receptor complex at the", "complex at the cell", "at the cell membrane", "cell membrane cell", "membrane cell death", "cell death signals are", "death signals are induced", "signals are induced by", "are induced by internalization", "induced by internalization associated", "by internalization associated fashion", "internalization associated fashion upon", "associated fashion upon the", "fashion upon the release", "upon the release of", "the release of ripk1", "release of ripk1 from", "of ripk1 from the", "ripk1 from the membrane", "from the membrane complex", "membrane complex micheau", "complex micheau o", "j 2003 schneider", "2003 schneider brachert", "schneider brachert w et", "brachert w et al.", "w et al. 2004", "al. 2004 tchikov", "2004 tchikov v", "tchikov v et al.", "v et al. 2011", "et al. 2011 .

tnfr1", "al. 2011 .

tnfr1 mediated", "2011 .

tnfr1 mediated transcriptional", ".

tnfr1 mediated transcriptional activity", "mediated transcriptional activity of", "transcriptional activity of nfkb", "activity of nfkb is", "of nfkb is both", "nfkb is both antiapoptotic", "is both antiapoptotic and", "both antiapoptotic and highly", "antiapoptotic and highly proinflammatory", "and highly proinflammatory and", "highly proinflammatory and thus", "proinflammatory and thus must", "and thus must be", "thus must be tightly", "must be tightly regulated", "be tightly regulated to", "tightly regulated to prevent", "regulated to prevent constitutive", "to prevent constitutive activation", "prevent constitutive activation that", "constitutive activation that leads", "activation that leads to", "that leads to persistent", "leads to persistent inflammation", "to persistent inflammation and", "persistent inflammation and cancer", "and cancer ward", "cancer ward c", "al. 1999 fujihara", "1999 fujihara s", "fujihara s et al.", "s et al. 2002", "al. 2002 pekalski", "2002 pekalski j", "pekalski j et al.", "j et al. 2013", "al. 2013 kankaanranta", "2013 kankaanranta h", "kankaanranta h et al.", "h et al. 2014", "al. 2014 shukla", "2014 shukla s", "shukla s and gupta", "s and gupta s", "and gupta s 2004", "s 2004 jackson", "2004 jackson bernitsas", "jackson bernitsas dg et", "bernitsas dg et al.", "dg et al. 2007", "al. 2007 zhang", "2007 zhang jy", "zhang jy et al.", "jy et al. 2007", "al. 2007 . multiple", "2007 . multiple mechanisms", ". multiple mechanisms normally", "multiple mechanisms normally ensure", "mechanisms normally ensure the", "normally ensure the proper", "ensure the proper control", "the proper control of", "proper control of nfkappab", "control of nfkappab activation", "of nfkappab activation including", "nfkappab activation including two", "activation including two negative", "including two negative feedback", "two negative feedback loops", "negative feedback loops mediated", "feedback loops mediated by", "loops mediated by nfkappab", "mediated by nfkappab inducible", "by nfkappab inducible inhibitors", "inducible inhibitors ikb", "inhibitors ikb alpha", "ikb alpha nfkbia", "nfkbia and ubiquitin", "and ubiquitin editing protein", "ubiquitin editing protein a20", "protein a20 he", "a20 he kl", "he kl & ting", "kl & ting at", "& ting at 2002", "at 2002 wertz", "2002 wertz ie", "wertz ie et al.", "ie et al. 2004", "al. 2004 vereecke", "2004 vereecke l", "vereecke l et al.", "l et al. 2009", "al. 2009 pekalski", "2009 pekalski j", "et al. 2013 .", "activation of tumor necrosis factor", "of tumor necrosis factor receptor", "tumor necrosis factor receptor 1", "factor receptor 1 tnfr1", "1 tnfr1 can", "tnfr1 can trigger multiple", "can trigger multiple signal transduction", "trigger multiple signal transduction pathways", "multiple signal transduction pathways to", "signal transduction pathways to induce", "transduction pathways to induce inflammation", "to induce inflammation cell", "induce inflammation cell proliferation", "cell proliferation survival or", "proliferation survival or cell", "or cell death ward", "cell death ward c", "death ward c et", "ward c et al. 1999", "et al. 1999 micheau", "al. 1999 micheau o", "1999 micheau o and", "micheau o and tschopp j", "o and tschopp j 2003", "tschopp j 2003 widera", "j 2003 widera d", "2003 widera d et", "widera d et al. 2006", "d et al. 2006 .", "et al. 2006 . whether", "al. 2006 . whether a", "2006 . whether a tnf", ". whether a tnf \u03b1", "whether a tnf \u03b1 stimulated", "a tnf \u03b1 stimulated cell", "tnf \u03b1 stimulated cell will", "\u03b1 stimulated cell will survive", "stimulated cell will survive or", "cell will survive or die", "will survive or die is", "survive or die is dependent", "or die is dependent on", "die is dependent on the", "is dependent on the cellular", "dependent on the cellular context.", "on the cellular context. tnf", "the cellular context. tnf \u03b1", "cellular context. tnf \u03b1 induced", "context. tnf \u03b1 induced signals", "tnf \u03b1 induced signals lead", "\u03b1 induced signals lead to", "induced signals lead to the", "signals lead to the activation", "lead to the activation of", "to the activation of transcriptional", "the activation of transcriptional factors", "activation of transcriptional factors such", "of transcriptional factors such as", "transcriptional factors such as nuclear", "factors such as nuclear factor", "such as nuclear factor kappa", "as nuclear factor kappa b", "factor kappa b nfkappab", "b nfkappab and", "nfkappab and activator protein", "activator protein 1 ap1", "ap1 ward c", "et al. 1999 widera", "al. 1999 widera d", "1999 widera d et", "et al. 2006 tsou", "al. 2006 tsou hk", "2006 tsou hk et", "tsou hk et al. 2012", "hk et al. 2012 .

", "et al. 2012 .

the", "al. 2012 .

the binding", "2012 .

the binding of", ".

the binding of tnf", "the binding of tnf \u03b1", "binding of tnf \u03b1 to", "of tnf \u03b1 to tnfr1", "tnf \u03b1 to tnfr1 leads", "\u03b1 to tnfr1 leads to", "to tnfr1 leads to recruitment", "tnfr1 leads to recruitment of", "leads to recruitment of the", "to recruitment of the adapter", "recruitment of the adapter protein", "of the adapter protein tnfr1", "the adapter protein tnfr1 associated", "adapter protein tnfr1 associated death", "protein tnfr1 associated death domain", "associated death domain tradd", "domain tradd and", "tradd and of receptor\u2011interacting", "and of receptor\u2011interacting protein 1", "receptor\u2011interacting protein 1 ripk1", "protein 1 ripk1 .", "1 ripk1 . tradd", "ripk1 . tradd subsequently recruits", ". tradd subsequently recruits also", "tradd subsequently recruits also tnf", "subsequently recruits also tnf receptor", "recruits also tnf receptor associated", "also tnf receptor associated factor", "tnf receptor associated factor 2", "associated factor 2 traf2", "factor 2 traf2 .", "2 traf2 . ripk1", "traf2 . ripk1 is promptly", ". ripk1 is promptly k63", "ripk1 is promptly k63 polyubiquitinated", "is promptly k63 polyubiquitinated which", "promptly k63 polyubiquitinated which results", "k63 polyubiquitinated which results in", "polyubiquitinated which results in the", "which results in the recruitment", "results in the recruitment of", "in the recruitment of the", "the recruitment of the tab2:tak1", "recruitment of the tab2:tak1 complex", "of the tab2:tak1 complex and", "the tab2:tak1 complex and the", "tab2:tak1 complex and the ikb", "complex and the ikb kinase", "the ikb kinase ikk", "kinase ikk complex", "ikk complex to tnfr1.", "complex to tnfr1. the activated", "to tnfr1. the activated ikk", "tnfr1. the activated ikk complex", "the activated ikk complex mediates", "activated ikk complex mediates phosphorylation", "ikk complex mediates phosphorylation of", "complex mediates phosphorylation of the", "mediates phosphorylation of the inhibitor", "phosphorylation of the inhibitor of", "of the inhibitor of nfkappab", "inhibitor of nfkappab ikb", "ikb which targets", "which targets ikb for ubiquitination", "targets ikb for ubiquitination and", "ikb for ubiquitination and subsequent", "for ubiquitination and subsequent degradation.", "ubiquitination and subsequent degradation. released", "and subsequent degradation. released nfkappab", "subsequent degradation. released nfkappab induces", "degradation. released nfkappab induces the", "released nfkappab induces the expression", "nfkappab induces the expression of", "induces the expression of a", "the expression of a variety", "expression of a variety of", "of a variety of genes", "a variety of genes including", "variety of genes including inflammation", "of genes including inflammation related", "genes including inflammation related genes", "including inflammation related genes and", "inflammation related genes and anti", "related genes and anti apoptotic", "genes and anti apoptotic genes", "and anti apoptotic genes encoding", "anti apoptotic genes encoding proteins", "apoptotic genes encoding proteins such", "genes encoding proteins such as", "encoding proteins such as inhibitor", "proteins such as inhibitor of", "such as inhibitor of apoptosis", "as inhibitor of apoptosis proteins", "inhibitor of apoptosis proteins ciap1/2", "apoptosis proteins ciap1/2 bcl", "proteins ciap1/2 bcl 2", "bcl 2 bcl xl", "2 bcl xl or", "bcl xl or cellular flice", "xl or cellular flice like", "or cellular flice like inhibitory", "cellular flice like inhibitory protein", "like inhibitory protein flip", "flip blonska m", "blonska m et al. 2005", "et al. 2005 ea", "al. 2005 ea ck", "2005 ea ck et", "ea ck et al. 2006", "et al. 2006 wu", "al. 2006 wu cj", "2006 wu cj et", "wu cj et al. 2006", "et al. 2006 chen", "al. 2006 chen c", "2006 chen c et", "chen c et al. 2000", "et al. 2000 manna", "al. 2000 manna sk", "2000 manna sk et", "manna sk et al. 2000", "et al. 2000 kreuz", "al. 2000 kreuz s", "2000 kreuz s et", "kreuz s et al. 2001", "et al. 2001 micheau", "al. 2001 micheau o", "2001 micheau o et", "micheau o et al. 2001", "o et al. 2001 .", "et al. 2001 . nfkb", "al. 2001 . nfkb mediated", "2001 . nfkb mediated inhibition", ". nfkb mediated inhibition of", "nfkb mediated inhibition of cell", "mediated inhibition of cell death", "inhibition of cell death also", "of cell death also involves", "cell death also involves attenuating", "death also involves attenuating tnf", "also involves attenuating tnf induced", "involves attenuating tnf induced activation", "attenuating tnf induced activation of", "tnf induced activation of c", "induced activation of c jun", "activation of c jun activating", "of c jun activating kinase", "jun activating kinase jnk", "activating kinase jnk .", "kinase jnk . whereas", "jnk . whereas transient activation", ". whereas transient activation of", "whereas transient activation of jnk", "transient activation of jnk upon", "activation of jnk upon tnf", "of jnk upon tnf treatment", "jnk upon tnf treatment is", "upon tnf treatment is associated", "tnf treatment is associated with", "treatment is associated with cellular", "is associated with cellular survival", "with cellular survival prolonged", "cellular survival prolonged jnk", "survival prolonged jnk activation", "prolonged jnk activation contributes to", "jnk activation contributes to cell", "activation contributes to cell death.", "contributes to cell death. however", "cell death. however as", "death. however as caspases", "however as caspases activate", "as caspases activate jnk quite", "caspases activate jnk quite efficiently", "jnk quite efficiently jnks", "quite efficiently jnks are", "efficiently jnks are also", "jnks are also regularly stimulated", "are also regularly stimulated in", "also regularly stimulated in course", "regularly stimulated in course of", "stimulated in course of apoptosis", "in course of apoptosis without", "course of apoptosis without being", "of apoptosis without being essential", "apoptosis without being essential for", "without being essential for cell", "being essential for cell death", "for cell death wicovsky", "cell death wicovsky a", "death wicovsky a et", "wicovsky a et al. 2007", "a et al. 2007 .", "et al. 2007 . ap1", "al. 2007 . ap1 mediated", "2007 . ap1 mediated gene", ". ap1 mediated gene induction", "ap1 mediated gene induction results", "mediated gene induction results from", "gene induction results from activation", "induction results from activation of", "results from activation of jnk", "from activation of jnk via", "activation of jnk via traf2", "jnk via traf2 not", "via traf2 not shown", "traf2 not shown here", "shown here tsou", "here tsou hk", "hk et al. 2012 .", "et al. 2012 . while", "al. 2012 . while pro", "2012 . while pro survival", ". while pro survival signaling", "while pro survival signaling is", "pro survival signaling is initiated", "survival signaling is initiated and", "signaling is initiated and regulated", "is initiated and regulated via", "initiated and regulated via the", "and regulated via the activated", "regulated via the activated tnfr1", "via the activated tnfr1 receptor", "the activated tnfr1 receptor complex", "activated tnfr1 receptor complex at", "tnfr1 receptor complex at the", "receptor complex at the cell", "complex at the cell membrane", "the cell membrane cell", "cell membrane cell death", "membrane cell death signals", "cell death signals are induced", "death signals are induced by", "signals are induced by internalization", "are induced by internalization associated", "induced by internalization associated fashion", "by internalization associated fashion upon", "internalization associated fashion upon the", "associated fashion upon the release", "fashion upon the release of", "upon the release of ripk1", "the release of ripk1 from", "release of ripk1 from the", "of ripk1 from the membrane", "ripk1 from the membrane complex", "the membrane complex micheau", "membrane complex micheau o", "complex micheau o and", "tschopp j 2003 schneider", "j 2003 schneider brachert", "2003 schneider brachert w", "schneider brachert w et al.", "brachert w et al. 2004", "et al. 2004 tchikov", "al. 2004 tchikov v", "2004 tchikov v et", "tchikov v et al. 2011", "v et al. 2011 .

tnfr1", "et al. 2011 .

tnfr1 mediated", "al. 2011 .

tnfr1 mediated transcriptional", "2011 .

tnfr1 mediated transcriptional activity", ".

tnfr1 mediated transcriptional activity of", "mediated transcriptional activity of nfkb", "transcriptional activity of nfkb is", "activity of nfkb is both", "of nfkb is both antiapoptotic", "nfkb is both antiapoptotic and", "is both antiapoptotic and highly", "both antiapoptotic and highly proinflammatory", "antiapoptotic and highly proinflammatory and", "and highly proinflammatory and thus", "highly proinflammatory and thus must", "proinflammatory and thus must be", "and thus must be tightly", "thus must be tightly regulated", "must be tightly regulated to", "be tightly regulated to prevent", "tightly regulated to prevent constitutive", "regulated to prevent constitutive activation", "to prevent constitutive activation that", "prevent constitutive activation that leads", "constitutive activation that leads to", "activation that leads to persistent", "that leads to persistent inflammation", "leads to persistent inflammation and", "to persistent inflammation and cancer", "inflammation and cancer ward", "and cancer ward c", "cancer ward c et", "et al. 1999 fujihara", "al. 1999 fujihara s", "1999 fujihara s et", "fujihara s et al. 2002", "et al. 2002 pekalski", "al. 2002 pekalski j", "2002 pekalski j et", "pekalski j et al. 2013", "et al. 2013 kankaanranta", "al. 2013 kankaanranta h", "2013 kankaanranta h et", "kankaanranta h et al. 2014", "et al. 2014 shukla", "al. 2014 shukla s", "2014 shukla s and", "shukla s and gupta s", "s and gupta s 2004", "gupta s 2004 jackson", "s 2004 jackson bernitsas", "2004 jackson bernitsas dg", "jackson bernitsas dg et al.", "bernitsas dg et al. 2007", "et al. 2007 zhang", "al. 2007 zhang jy", "2007 zhang jy et", "zhang jy et al. 2007", "jy et al. 2007 .", "et al. 2007 . multiple", "al. 2007 . multiple mechanisms", "2007 . multiple mechanisms normally", ". multiple mechanisms normally ensure", "multiple mechanisms normally ensure the", "mechanisms normally ensure the proper", "normally ensure the proper control", "ensure the proper control of", "the proper control of nfkappab", "proper control of nfkappab activation", "control of nfkappab activation including", "of nfkappab activation including two", "nfkappab activation including two negative", "activation including two negative feedback", "including two negative feedback loops", "two negative feedback loops mediated", "negative feedback loops mediated by", "feedback loops mediated by nfkappab", "loops mediated by nfkappab inducible", "mediated by nfkappab inducible inhibitors", "nfkappab inducible inhibitors ikb", "inducible inhibitors ikb alpha", "alpha nfkbia and", "nfkbia and ubiquitin editing", "and ubiquitin editing protein a20", "editing protein a20 he", "protein a20 he kl", "a20 he kl &", "he kl & ting at", "kl & ting at 2002", "ting at 2002 wertz", "at 2002 wertz ie", "2002 wertz ie et", "wertz ie et al. 2004", "et al. 2004 vereecke", "al. 2004 vereecke l", "2004 vereecke l et", "vereecke l et al. 2009", "et al. 2009 pekalski", "al. 2009 pekalski j", "2009 pekalski j et", "j et al. 2013 ." ] }, { "record_id": "GLY_000594_1_417", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5358346", "r hsa", "hsa 5358346", "r hsa 5358346" ] }, { "record_id": "GLY_000594_1_417", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hedgehog ligand", "ligand biogenesis", "hedgehog ligand biogenesis", "mammalian genomes", "genomes encode", "encode three", "three hedgehog", "hedgehog ligands", "sonic hedgehog", "indian hedgehog", "and desert", "desert hedgehog", "dhh .", "these secreted", "secreted morphogens", "morphogens can", "can remain", "remain associated", "associated with", "with lipid", "lipid rafts", "rafts on", "on the", "the surface", "surface of", "of the", "the secreting", "secreting cell", "cell and", "and affect", "affect developmental", "developmental processes", "processes in", "in adjacent", "adjacent cells.", "cells. alternatively", "they can", "can be", "be released", "released by", "by proteolysis", "proteolysis or", "or packaging", "packaging into", "into vesicles", "vesicles or", "or lipoprotein", "lipoprotein particles", "particles and", "and dispersed", "dispersed to", "to act", "act on", "on distant", "distant cells.", "cells. shh", "shh activity", "activity is", "is required", "required for", "for organization", "organization of", "the limb", "limb bud", "notochord and", "and neural", "neural plate", "ihh regulates", "regulates bone", "bone and", "and cartilage", "cartilage development", "development and", "and is", "is partially", "partially redundant", "redundant with", "with shh", "and dhh", "dhh contributes", "contributes to", "to germ", "germ cell", "cell development", "development in", "in the", "the testis", "testis and", "and formation", "formation of", "the peripheral", "peripheral nerve", "nerve sheath", "reviewed in", "in pan", "pan et", "et al", "2013 .", "

despite divergent", "divergent biological", "biological roles", "all hh", "hh ligands", "ligands are", "are subject", "subject to", "to proteolytic", "proteolytic processing", "processing and", "and lipid", "lipid modification", "modification during", "during transit", "transit to", "to the", "in gallet", "2011 .", "precursor hh", "hh undergoes", "undergoes autoproteolytic", "autoproteolytic cleavage", "cleavage mediated", "mediated by", "by the", "the c", "c terminal", "terminal region", "region to", "to yield", "yield an", "an amino", "amino terminal", "terminal peptide", "peptide hh", "hh np", "also referred", "referred to", "to as", "as hh", "hh n", "chen et", "no other", "other well", "well defined", "defined role", "role for", "for the", "region of", "of hh", "hh has", "has been", "been identified", "and the", "the secreted", "secreted hh", "np is", "is responsible", "responsible for", "for all", "hh signaling", "signaling activity.", "is modified", "modified with", "with cholesterol", "cholesterol and", "and palmitic", "palmitic acid", "acid during", "transit through", "through the", "the secretory", "secretory system", "and both", "both modifications", "modifications contribute", "contribute to", "the activity", "activity of", "the ligand", "porter et", "pepinsky et", "chamoun et", "2001 .", "

at the", "the cell", "cell surface", "np remains", "remains associated", "with the", "cell membrane", "membrane by", "by virtue", "virtue of", "of its", "its lipid", "lipid modifications", "which promote", "promote clustering", "clustering of", "np into", "into lipid", "callejo et", "peters et", "2004 .", "long range", "range dispersal", "dispersal of", "np depends", "depends on", "the untethering", "untethering of", "ligand from", "from the", "the membrane", "membrane through", "through a", "a variety", "variety of", "of mechanisms.", "these include", "include release", "release of", "of monomers", "monomers through", "the combined", "combined activity", "the transmembrane", "transmembrane protein", "protein dispatched", "secreted protein", "protein scube2", "assembly into", "into soluble", "soluble multimers", "multimers or", "or apolipoprotein", "apolipoprotein particles", "particles or", "or release", "release on", "of exovesicles", "vyas et", "tukachinsky et", "chen 2004", "zeng et", "in briscoe", "briscoe and", "and therond", "mammalian genomes encode", "genomes encode three", "encode three hedgehog", "three hedgehog ligands", "ligands sonic", "hedgehog shh", "hedgehog ihh", "ihh and", "and desert hedgehog", "hedgehog dhh", ". these", "these secreted morphogens", "secreted morphogens can", "morphogens can remain", "can remain associated", "remain associated with", "associated with lipid", "with lipid rafts", "lipid rafts on", "rafts on the", "on the surface", "the surface of", "surface of the", "of the secreting", "the secreting cell", "secreting cell and", "cell and affect", "and affect developmental", "affect developmental processes", "developmental processes in", "processes in adjacent", "in adjacent cells.", "adjacent cells. alternatively", "alternatively they", "they can be", "can be released", "be released by", "released by proteolysis", "by proteolysis or", "proteolysis or packaging", "or packaging into", "packaging into vesicles", "into vesicles or", "vesicles or lipoprotein", "or lipoprotein particles", "lipoprotein particles and", "particles and dispersed", "and dispersed to", "dispersed to act", "to act on", "act on distant", "on distant cells.", "distant cells. shh", "cells. shh activity", "shh activity is", "activity is required", "is required for", "required for organization", "for organization of", "organization of the", "of the limb", "the limb bud", "bud notochord", "notochord and neural", "and neural plate", "plate ihh", "ihh regulates bone", "regulates bone and", "bone and cartilage", "and cartilage development", "cartilage development and", "development and is", "and is partially", "is partially redundant", "partially redundant with", "redundant with shh", "shh and", "and dhh contributes", "dhh contributes to", "contributes to germ", "to germ cell", "germ cell development", "cell development in", "development in the", "in the testis", "the testis and", "testis and formation", "and formation of", "formation of the", "of the peripheral", "the peripheral nerve", "peripheral nerve sheath", "sheath reviewed", "reviewed in pan", "in pan et", "pan et al", "al 2013", ".

despite", "

despite divergent biological", "divergent biological roles", "roles all", "all hh ligands", "hh ligands are", "ligands are subject", "are subject to", "subject to proteolytic", "to proteolytic processing", "proteolytic processing and", "processing and lipid", "and lipid modification", "lipid modification during", "modification during transit", "during transit to", "transit to the", "to the surface", "cell reviewed", "reviewed in gallet", "gallet 2011", ". precursor", "precursor hh undergoes", "hh undergoes autoproteolytic", "undergoes autoproteolytic cleavage", "autoproteolytic cleavage mediated", "cleavage mediated by", "mediated by the", "by the c", "the c terminal", "c terminal region", "terminal region to", "region to yield", "to yield an", "yield an amino", "an amino terminal", "amino terminal peptide", "terminal peptide hh", "peptide hh np", "np also", "also referred to", "referred to as", "to as hh", "as hh n", "chen et al", "al 2011", ". no", "no other well", "other well defined", "well defined role", "defined role for", "role for the", "for the c", "terminal region of", "region of hh", "of hh has", "hh has been", "has been identified", "identified and", "and the secreted", "the secreted hh", "secreted hh np", "hh np is", "np is responsible", "is responsible for", "responsible for all", "for all hh", "all hh signaling", "hh signaling activity.", "activity. hh", "np is modified", "is modified with", "modified with cholesterol", "with cholesterol and", "cholesterol and palmitic", "and palmitic acid", "palmitic acid during", "acid during transit", "during transit through", "transit through the", "through the secretory", "the secretory system", "system and", "and both modifications", "both modifications contribute", "modifications contribute to", "contribute to the", "to the activity", "the activity of", "activity of the", "of the ligand", "ligand porter", "porter et al", "al 1996", "1996 pepinsky", "pepinsky et al", "al 1998", "1998 chamoun", "chamoun et al", "al 2001", ".

at", "

at the cell", "the cell surface", "surface hh", "hh np remains", "np remains associated", "remains associated with", "associated with the", "with the secreting", "secreting cell membrane", "cell membrane by", "membrane by virtue", "by virtue of", "virtue of its", "of its lipid", "its lipid modifications", "modifications which", "which promote clustering", "promote clustering of", "clustering of hh", "of hh np", "hh np into", "np into lipid", "into lipid rafts", "rafts callejo", "callejo et al", "al 2006", "2006 peters", "peters et al", "al 2004", ". long", "long range dispersal", "range dispersal of", "dispersal of hh", "hh np depends", "np depends on", "depends on the", "on the untethering", "the untethering of", "untethering of the", "the ligand from", "ligand from the", "from the membrane", "the membrane through", "membrane through a", "through a variety", "a variety of", "variety of mechanisms.", "mechanisms. these", "these include release", "include release of", "release of monomers", "of monomers through", "monomers through the", "through the combined", "the combined activity", "combined activity of", "of the transmembrane", "the transmembrane protein", "transmembrane protein dispatched", "dispatched disp2", "disp2 and", "the secreted protein", "secreted protein scube2", "scube2 assembly", "assembly into soluble", "into soluble multimers", "soluble multimers or", "multimers or apolipoprotein", "or apolipoprotein particles", "apolipoprotein particles or", "particles or release", "or release on", "release on the", "surface of exovesicles", "exovesicles vyas", "vyas et al", "al 2008", "2008 tukachinsky", "tukachinsky et al", "al 2012", "2012 chen", "2004 zeng", "zeng et al", "2001 reviewed", "reviewed in briscoe", "in briscoe and", "briscoe and therond", "therond 2013", "mammalian genomes encode three", "genomes encode three hedgehog", "encode three hedgehog ligands", "hedgehog ligands sonic", "ligands sonic hedgehog", "sonic hedgehog shh", "shh indian", "indian hedgehog ihh", "ihh and desert", "desert hedgehog dhh", "hedgehog dhh .", "dhh . these", ". these secreted", "these secreted morphogens can", "secreted morphogens can remain", "morphogens can remain associated", "can remain associated with", "remain associated with lipid", "associated with lipid rafts", "with lipid rafts on", "lipid rafts on the", "rafts on the surface", "on the surface of", "the surface of the", "surface of the secreting", "of the secreting cell", "the secreting cell and", "secreting cell and affect", "cell and affect developmental", "and affect developmental processes", "affect developmental processes in", "developmental processes in adjacent", "processes in adjacent cells.", "in adjacent cells. alternatively", "cells. alternatively they", "alternatively they can", "they can be released", "can be released by", "be released by proteolysis", "released by proteolysis or", "by proteolysis or packaging", "proteolysis or packaging into", "or packaging into vesicles", "packaging into vesicles or", "into vesicles or lipoprotein", "vesicles or lipoprotein particles", "or lipoprotein particles and", "lipoprotein particles and dispersed", "particles and dispersed to", "and dispersed to act", "dispersed to act on", "to act on distant", "act on distant cells.", "on distant cells. shh", "distant cells. shh activity", "cells. shh activity is", "shh activity is required", "activity is required for", "is required for organization", "required for organization of", "for organization of the", "organization of the limb", "of the limb bud", "limb bud notochord", "bud notochord and", "notochord and neural plate", "neural plate ihh", "plate ihh regulates", "ihh regulates bone and", "regulates bone and cartilage", "bone and cartilage development", "and cartilage development and", "cartilage development and is", "development and is partially", "and is partially redundant", "is partially redundant with", "partially redundant with shh", "with shh and", "shh and dhh", "and dhh contributes to", "dhh contributes to germ", "contributes to germ cell", "to germ cell development", "germ cell development in", "cell development in the", "development in the testis", "in the testis and", "the testis and formation", "testis and formation of", "and formation of the", "formation of the peripheral", "of the peripheral nerve", "the peripheral nerve sheath", "nerve sheath reviewed", "sheath reviewed in", "reviewed in pan et", "in pan et al", "et al 2013", "al 2013 .", "2013 .

despite", ".

despite divergent", "

despite divergent biological roles", "biological roles all", "roles all hh", "all hh ligands are", "hh ligands are subject", "ligands are subject to", "are subject to proteolytic", "subject to proteolytic processing", "to proteolytic processing and", "proteolytic processing and lipid", "processing and lipid modification", "and lipid modification during", "lipid modification during transit", "modification during transit to", "during transit to the", "transit to the surface", "to the surface of", "secreting cell reviewed", "cell reviewed in", "in gallet 2011", "gallet 2011 .", "2011 . precursor", ". precursor hh", "precursor hh undergoes autoproteolytic", "hh undergoes autoproteolytic cleavage", "undergoes autoproteolytic cleavage mediated", "autoproteolytic cleavage mediated by", "cleavage mediated by the", "mediated by the c", "by the c terminal", "the c terminal region", "c terminal region to", "terminal region to yield", "region to yield an", "to yield an amino", "yield an amino terminal", "an amino terminal peptide", "amino terminal peptide hh", "terminal peptide hh np", "hh np also", "np also referred", "also referred to as", "referred to as hh", "to as hh n", "n chen", "et al 2011", "al 2011 .", "2011 . no", ". no other", "no other well defined", "other well defined role", "well defined role for", "defined role for the", "role for the c", "for the c terminal", "c terminal region of", "terminal region of hh", "region of hh has", "of hh has been", "hh has been identified", "been identified and", "identified and the", "and the secreted hh", "the secreted hh np", "secreted hh np is", "hh np is responsible", "np is responsible for", "is responsible for all", "responsible for all hh", "for all hh signaling", "all hh signaling activity.", "signaling activity. hh", "activity. hh np", "hh np is modified", "np is modified with", "is modified with cholesterol", "modified with cholesterol and", "with cholesterol and palmitic", "cholesterol and palmitic acid", "and palmitic acid during", "palmitic acid during transit", "acid during transit through", "during transit through the", "transit through the secretory", "through the secretory system", "secretory system and", "system and both", "and both modifications contribute", "both modifications contribute to", "modifications contribute to the", "contribute to the activity", "to the activity of", "the activity of the", "activity of the ligand", "the ligand porter", "ligand porter et", "et al 1996", "1996 pepinsky et", "et al 1998", "1998 chamoun et", "et al 2001", "al 2001 .", "2001 .

at", ".

at the", "

at the cell surface", "cell surface hh", "surface hh np", "hh np remains associated", "np remains associated with", "remains associated with the", "associated with the secreting", "with the secreting cell", "the secreting cell membrane", "secreting cell membrane by", "cell membrane by virtue", "membrane by virtue of", "by virtue of its", "virtue of its lipid", "of its lipid modifications", "lipid modifications which", "modifications which promote", "which promote clustering of", "promote clustering of hh", "clustering of hh np", "of hh np into", "hh np into lipid", "np into lipid rafts", "lipid rafts callejo", "rafts callejo et", "et al 2006", "2006 peters et", "et al 2004", "al 2004 .", "2004 . long", ". long range", "long range dispersal of", "range dispersal of hh", "dispersal of hh np", "of hh np depends", "hh np depends on", "np depends on the", "depends on the untethering", "on the untethering of", "the untethering of the", "untethering of the ligand", "of the ligand from", "the ligand from the", "ligand from the membrane", "from the membrane through", "the membrane through a", "membrane through a variety", "through a variety of", "a variety of mechanisms.", "of mechanisms. these", "mechanisms. these include", "these include release of", "include release of monomers", "release of monomers through", "of monomers through the", "monomers through the combined", "through the combined activity", "the combined activity of", "combined activity of the", "activity of the transmembrane", "of the transmembrane protein", "the transmembrane protein dispatched", "protein dispatched disp2", "disp2 and the", "and the secreted protein", "the secreted protein scube2", "protein scube2 assembly", "scube2 assembly into", "assembly into soluble multimers", "into soluble multimers or", "soluble multimers or apolipoprotein", "multimers or apolipoprotein particles", "or apolipoprotein particles or", "apolipoprotein particles or release", "particles or release on", "or release on the", "release on the surface", "the surface of exovesicles", "of exovesicles vyas", "exovesicles vyas et", "et al 2008", "2008 tukachinsky et", "et al 2012", "2012 chen 2004", "chen 2004 zeng", "2004 zeng et", "2001 reviewed in", "reviewed in briscoe and", "in briscoe and therond", "and therond 2013", "therond 2013 .", "mammalian genomes encode three hedgehog", "genomes encode three hedgehog ligands", "three hedgehog ligands sonic", "hedgehog ligands sonic hedgehog", "shh indian hedgehog", "hedgehog ihh and", "ihh and desert hedgehog", "and desert hedgehog dhh", "desert hedgehog dhh .", "dhh . these secreted", ". these secreted morphogens", "these secreted morphogens can remain", "secreted morphogens can remain associated", "morphogens can remain associated with", "can remain associated with lipid", "remain associated with lipid rafts", "associated with lipid rafts on", "with lipid rafts on the", "lipid rafts on the surface", "rafts on the surface of", "on the surface of the", "the surface of the secreting", "surface of the secreting cell", "of the secreting cell and", "the secreting cell and affect", "secreting cell and affect developmental", "cell and affect developmental processes", "and affect developmental processes in", "affect developmental processes in adjacent", "developmental processes in adjacent cells.", "processes in adjacent cells. alternatively", "adjacent cells. alternatively they", "cells. alternatively they can", "alternatively they can be", "they can be released by", "can be released by proteolysis", "be released by proteolysis or", "released by proteolysis or packaging", "by proteolysis or packaging into", "proteolysis or packaging into vesicles", "or packaging into vesicles or", "packaging into vesicles or lipoprotein", "into vesicles or lipoprotein particles", "vesicles or lipoprotein particles and", "or lipoprotein particles and dispersed", "lipoprotein particles and dispersed to", "particles and dispersed to act", "and dispersed to act on", "dispersed to act on distant", "to act on distant cells.", "act on distant cells. shh", "on distant cells. shh activity", "distant cells. shh activity is", "cells. shh activity is required", "shh activity is required for", "activity is required for organization", "is required for organization of", "required for organization of the", "for organization of the limb", "organization of the limb bud", "the limb bud notochord", "limb bud notochord and", "bud notochord and neural", "and neural plate ihh", "neural plate ihh regulates", "plate ihh regulates bone", "ihh regulates bone and cartilage", "regulates bone and cartilage development", "bone and cartilage development and", "and cartilage development and is", "cartilage development and is partially", "development and is partially redundant", "and is partially redundant with", "is partially redundant with shh", "redundant with shh and", "with shh and dhh", "shh and dhh contributes", "and dhh contributes to germ", "dhh contributes to germ cell", "contributes to germ cell development", "to germ cell development in", "germ cell development in the", "cell development in the testis", "development in the testis and", "in the testis and formation", "the testis and formation of", "testis and formation of the", "and formation of the peripheral", "formation of the peripheral nerve", "of the peripheral nerve sheath", "peripheral nerve sheath reviewed", "nerve sheath reviewed in", "sheath reviewed in pan", "reviewed in pan et al", "pan et al 2013", "et al 2013 .", "2013 .

despite divergent", ".

despite divergent biological", "divergent biological roles all", "biological roles all hh", "roles all hh ligands", "all hh ligands are subject", "hh ligands are subject to", "ligands are subject to proteolytic", "are subject to proteolytic processing", "subject to proteolytic processing and", "to proteolytic processing and lipid", "proteolytic processing and lipid modification", "processing and lipid modification during", "and lipid modification during transit", "lipid modification during transit to", "modification during transit to the", "during transit to the surface", "transit to the surface of", "to the surface of the", "the secreting cell reviewed", "secreting cell reviewed in", "cell reviewed in gallet", "reviewed in gallet 2011", "in gallet 2011 .", "2011 . precursor hh", ". precursor hh undergoes", "precursor hh undergoes autoproteolytic cleavage", "hh undergoes autoproteolytic cleavage mediated", "undergoes autoproteolytic cleavage mediated by", "autoproteolytic cleavage mediated by the", "cleavage mediated by the c", "mediated by the c terminal", "by the c terminal region", "the c terminal region to", "c terminal region to yield", "terminal region to yield an", "region to yield an amino", "to yield an amino terminal", "yield an amino terminal peptide", "an amino terminal peptide hh", "amino terminal peptide hh np", "peptide hh np also", "hh np also referred", "np also referred to", "also referred to as hh", "referred to as hh n", "hh n chen", "n chen et", "chen et al 2011", "et al 2011 .", "2011 . no other", ". no other well", "no other well defined role", "other well defined role for", "well defined role for the", "defined role for the c", "role for the c terminal", "for the c terminal region", "the c terminal region of", "c terminal region of hh", "terminal region of hh has", "region of hh has been", "of hh has been identified", "has been identified and", "been identified and the", "identified and the secreted", "and the secreted hh np", "the secreted hh np is", "secreted hh np is responsible", "hh np is responsible for", "np is responsible for all", "is responsible for all hh", "responsible for all hh signaling", "for all hh signaling activity.", "hh signaling activity. hh", "signaling activity. hh np", "activity. hh np is", "hh np is modified with", "np is modified with cholesterol", "is modified with cholesterol and", "modified with cholesterol and palmitic", "with cholesterol and palmitic acid", "cholesterol and palmitic acid during", "and palmitic acid during transit", "palmitic acid during transit through", "acid during transit through the", "during transit through the secretory", "transit through the secretory system", "the secretory system and", "secretory system and both", "system and both modifications", "and both modifications contribute to", "both modifications contribute to the", "modifications contribute to the activity", "contribute to the activity of", "to the activity of the", "the activity of the ligand", "of the ligand porter", "the ligand porter et", "ligand porter et al", "porter et al 1996", "al 1996 pepinsky", "1996 pepinsky et al", "pepinsky et al 1998", "al 1998 chamoun", "1998 chamoun et al", "chamoun et al 2001", "et al 2001 .", "2001 .

at the", ".

at the cell", "the cell surface hh", "cell surface hh np", "surface hh np remains", "hh np remains associated with", "np remains associated with the", "remains associated with the secreting", "associated with the secreting cell", "with the secreting cell membrane", "the secreting cell membrane by", "secreting cell membrane by virtue", "cell membrane by virtue of", "membrane by virtue of its", "by virtue of its lipid", "virtue of its lipid modifications", "its lipid modifications which", "lipid modifications which promote", "modifications which promote clustering", "which promote clustering of hh", "promote clustering of hh np", "clustering of hh np into", "of hh np into lipid", "hh np into lipid rafts", "into lipid rafts callejo", "lipid rafts callejo et", "rafts callejo et al", "callejo et al 2006", "al 2006 peters", "2006 peters et al", "peters et al 2004", "et al 2004 .", "2004 . long range", ". long range dispersal", "long range dispersal of hh", "range dispersal of hh np", "dispersal of hh np depends", "of hh np depends on", "hh np depends on the", "np depends on the untethering", "depends on the untethering of", "on the untethering of the", "the untethering of the ligand", "untethering of the ligand from", "of the ligand from the", "the ligand from the membrane", "ligand from the membrane through", "from the membrane through a", "the membrane through a variety", "membrane through a variety of", "through a variety of mechanisms.", "variety of mechanisms. these", "of mechanisms. these include", "mechanisms. these include release", "these include release of monomers", "include release of monomers through", "release of monomers through the", "of monomers through the combined", "monomers through the combined activity", "through the combined activity of", "the combined activity of the", "combined activity of the transmembrane", "activity of the transmembrane protein", "of the transmembrane protein dispatched", "transmembrane protein dispatched disp2", "dispatched disp2 and", "disp2 and the secreted", "and the secreted protein scube2", "secreted protein scube2 assembly", "protein scube2 assembly into", "scube2 assembly into soluble", "assembly into soluble multimers or", "into soluble multimers or apolipoprotein", "soluble multimers or apolipoprotein particles", "multimers or apolipoprotein particles or", "or apolipoprotein particles or release", "apolipoprotein particles or release on", "particles or release on the", "or release on the surface", "release on the surface of", "on the surface of exovesicles", "surface of exovesicles vyas", "of exovesicles vyas et", "exovesicles vyas et al", "vyas et al 2008", "al 2008 tukachinsky", "2008 tukachinsky et al", "tukachinsky et al 2012", "al 2012 chen", "chen 2004 zeng et", "2004 zeng et al", "zeng et al 2001", "al 2001 reviewed", "2001 reviewed in briscoe", "reviewed in briscoe and therond", "briscoe and therond 2013", "and therond 2013 ." ] }, { "record_id": "GLY_000594_1_418", 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ott and herrmann 2010", "and herrmann 2010 agrawal", "herrmann 2010 agrawal and", "2010 agrawal and sharma", "agrawal and sharma 2012 .", "and sharma 2012 . tufm:gdp", "sharma 2012 . tufm:gdp is", "2012 . tufm:gdp is regenerated", ". tufm:gdp is regenerated to", "tufm:gdp is regenerated to tufm:gtp", "is regenerated to tufm:gtp by", "regenerated to tufm:gtp by the", "to tufm:gtp by the guanine", "tufm:gtp by the guanine nucleotide", "by the guanine nucleotide exchange", "the guanine nucleotide exchange factor", "guanine nucleotide exchange factor tsfm", "exchange factor tsfm ef", "factor tsfm ef ts", "ef ts ef tsmt", "ts ef tsmt ." ] }, { "record_id": "GLY_000594_1_428", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5419276", "r hsa", "hsa 5419276", "r hsa 5419276" ] }, { "record_id": "GLY_000594_1_428", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitochondrial translation", "translation 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spremulli 2012", "spremulli 2012 .", "2012 . gtp", ". gtp is", "gtp is hydrolyzed", "hydrolyzed and", "and the aminoacyl", "the aminoacyl bond", "aminoacyl bond between", "bond between the", "between the translated", "the translated polypeptide", "translated polypeptide and", "polypeptide and the", "and the final", "the final trna", "final trna at", "trna at the", "at the p", "the p site", "p site is", "site is hydrolyzed", "is hydrolyzed by", "hydrolyzed by the", "by the 39s", "the 39s ribosomal", "39s ribosomal subunit", "subunit releasing", "releasing the translated", "the translated polypeptide.", "translated polypeptide. mrrf", "mrrf rrf", "rrf and", "gfm2:gtp ef", "g2mt:gtp then", "then act to", "act to release", "to release the", "release the remaining", "the remaining trna", "remaining trna and", "trna and mrna", "and mrna from", "mrna from the", "from the ribosome", "the ribosome and", "ribosome and dissociate", "and dissociate the", "dissociate the 55s", "the 55s ribosome", 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.", "spremulli 2012 . gtp", "2012 . gtp is", ". gtp is hydrolyzed", "is hydrolyzed and", "hydrolyzed and the", "and the aminoacyl bond", "the aminoacyl bond between", "aminoacyl bond between the", "bond between the translated", "between the translated polypeptide", "the translated polypeptide and", "translated polypeptide and the", "polypeptide and the final", "and the final trna", "the final trna at", "final trna at the", "trna at the p", "at the p site", "the p site is", "p site is hydrolyzed", "site is hydrolyzed by", "is hydrolyzed by the", "hydrolyzed by the 39s", "by the 39s ribosomal", "the 39s ribosomal subunit", "ribosomal subunit releasing", "subunit releasing the", "releasing the translated polypeptide.", "the translated polypeptide. mrrf", "polypeptide. mrrf rrf", "rrf and gfm2:gtp", "and gfm2:gtp ef", "gfm2:gtp ef g2mt:gtp", "ef g2mt:gtp then", "g2mt:gtp then act", "then act to release", "act to release the", "to release the remaining", "release the remaining trna", "the remaining trna and", "remaining trna and mrna", "trna and mrna from", "and mrna from the", "mrna from the ribosome", "from the ribosome and", "the ribosome and dissociate", "ribosome and dissociate the", "and dissociate the 55s", "dissociate the 55s ribosome", "the 55s ribosome into", "55s ribosome into 28s", "ribosome into 28s and", "into 28s and 39s", "28s and 39s subunits.", "translation is terminated when mtrf1l:gtp", "terminated when mtrf1l:gtp mtrf1a:gtp", "mtrf1l:gtp mtrf1a:gtp recognizes", "mtrf1a:gtp recognizes a uaa", "recognizes a uaa or uag", "a uaa or uag termination", "uaa or uag termination codon", "or uag termination codon in", "uag termination codon in the", "termination codon in the mrna", "codon in the mrna at", "in the mrna at the", "the mrna at the a", "mrna at the a site", "at the a site of", "the a site of the", "a site of the ribosome", "of the ribosome soleimanpour", "the ribosome soleimanpour lichaei", "ribosome soleimanpour lichaei et", "soleimanpour lichaei et al. 2007", "et al. 2007 reviewed", "al. 2007 reviewed in", "2007 reviewed in richter", "reviewed in richter et al.", "in richter et al. 2010", "et al. 2010 chrzanowska", "al. 2010 chrzanowska lightowlers", "2010 chrzanowska lightowlers et", "chrzanowska lightowlers et al. 2011.", "lightowlers et al. 2011. christian", "et al. 2011. christian and", "al. 2011. christian and spremulli", "2011. christian and spremulli 2012", "christian and spremulli 2012 .", "and spremulli 2012 . gtp", "spremulli 2012 . gtp is", "2012 . gtp is hydrolyzed", "gtp is hydrolyzed and", "is hydrolyzed and the", "hydrolyzed and the aminoacyl", "and the aminoacyl bond between", "the aminoacyl bond between the", "aminoacyl bond between the translated", "bond between the translated polypeptide", "between the translated polypeptide and", "the translated polypeptide and the", "translated polypeptide and the final", "polypeptide and the final trna", "and the final trna at", "the final trna at the", "final trna at the p", "trna at the p site", "at the p site is", "the p site is hydrolyzed", "p site is hydrolyzed by", "site is hydrolyzed by the", "is hydrolyzed by the 39s", "hydrolyzed by the 39s ribosomal", "by the 39s ribosomal subunit", "39s ribosomal subunit releasing", "ribosomal subunit releasing the", "subunit releasing the translated", "releasing the translated polypeptide. mrrf", "translated polypeptide. mrrf rrf", "mrrf rrf and", "and gfm2:gtp ef g2mt:gtp", "ef g2mt:gtp then act", "g2mt:gtp then act to", "then act to release the", "act to release the remaining", "to release the remaining trna", "release the remaining trna and", "the remaining trna and mrna", "remaining trna and mrna from", "trna and mrna from the", "and mrna from the ribosome", "mrna from the ribosome and", "from the ribosome and dissociate", "the ribosome and dissociate the", "ribosome and dissociate the 55s", "and dissociate the 55s ribosome", "dissociate the 55s ribosome into", "the 55s ribosome into 28s", "55s ribosome into 28s and", "ribosome into 28s and 39s", "into 28s and 39s subunits." ] }, { "record_id": "GLY_000594_1_429", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5423646", "r hsa", "hsa 5423646", "r hsa 5423646" ] }, { "record_id": "GLY_000594_1_429", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "aflatoxin activation", "activation and", "and detoxification", "aflatoxin activation and", "activation and detoxification", "aflatoxin activation and detoxification", "aflatoxins are", "are among", "among the", "the principal", "principal mycotoxins", "mycotoxins produced", "produced as", "as secondary", "secondary metabolites", "metabolites by", "by the", "the molds", "molds aspergillus", "aspergillus flavus", "flavus and", "and aspergillus", "aspergillus parasiticus", "parasiticus that", "that contaminate", "contaminate economically", "economically important", "important food", "food and", "and feed", "feed crops", "wild &", "& turner", "turner 2002", "2002 .", ". aflatoxin", "aflatoxin b1", "is the", "the most", "most potent", "potent naturally", "naturally occurring", "occurring carcinogen", "carcinogen known", "known and", "and is", "is also", "also an", "an immunosuppressant.", "immunosuppressant. it", "it is", "is a", "a potent", "potent hepatocarcinogenic", "hepatocarcinogenic agent", "agent in", "in many", "many species", "and has", "has been", "been implicated", "implicated in", "in the", "the etiology", "etiology of", "of human", "human hepatocellular", "hepatocellular carcinoma.", "carcinoma. poultry", "especially turkeys", "are extremely", "extremely sensitive", "sensitive to", "to the", "the toxic", "toxic and", "and carcinogenic", "carcinogenic action", "action of", "of afb1", "afb1 present", "present in", "in animal", "animal feed", "resulting in", "in multi", "multi million", "million dollar", "dollar losses", "losses to", "the industry.", "industry. discerning", "discerning the", "the biochemical", "biochemical and", "and molecular", "molecular mechanisms", "mechanisms of", "of this", "this extreme", "extreme sensitivity", "sensitivity of", "of poultry", "poultry to", "to afb1", "afb1 will", "will help", "help with", "with the", "the development", "development of", "of new", "new strategies", "strategies to", "to increase", "increase aflatoxin", "aflatoxin resistance", "rawal et", "et al.", "al. 2010", "diaz &", "& murcia", "murcia 2011", "2011 .


afb1", ".


afb1 has", "has one", "one major", "major genotoxic", "genotoxic metabolic", "metabolic fate", "conversion to", "to afxbo", "and several", "several others", "others that", "that are", "are less", "less mutagenic", "mutagenic but", "but that", "that can", "can still", "still be", "be quite", "quite toxic.", "toxic. afb1", "afb1 can", "can be", "be oxidised", "oxidised to", "toxic afb1", "afb1 exo", "exo 8", "8 9", "9 epoxide", "product by", "by several", "several cytochrome", "cytochrome p450", "p450 enzymes", "especially p450", "p450 3a4", "3a4 in", "the liver.", "liver. this", "this 8", "epoxide can", "can react", "react with", "the n7", "n7 atom", "atom of", "of a", "a guanyl", "guanyl base", "base of", "of dna", "dna to", "to produce", "produce adducts", "adducts by", "by intercalating", "intercalating between", "between dna", "dna base", "base pairs.", "pairs. the", "the exo", "exo epoxide", "epoxide is", "is unstable", "unstable in", "in solution", "and can", "react spontaneously", "spontaneously to", "to form", "form a", "a diol", "diol that", "that is", "is no", "no longer", "longer reactive", "reactive with", "with dna.", "dna. the", "the diol", "diol product", "product in", "in turn", "turn undergoes", "undergoes base", "base catalysed", "catalysed rearrangement", "rearrangement to", "to a", "a dialdehyde", "dialdehyde that", "with protein", "protein lysine", "lysine residues.", "residues. afb1", "can also", "also be", "be metabolised", "metabolised to", "to products", "which have", "have far", "far less", "less genotoxic", "genotoxic consequences", "consequences than", "than afb1.", "afb1. the", "the main", "main route", "route of", "of detoxification", "detoxification of", "afb1 is", "is conjugation", "conjugation of", "of its", "its reactive", "reactive 8", "epoxide form", "form with", "with glutathione", "gsh .", ". this", "this reaction", "reaction is", "is carried", "carried out", "out by", "by trimeric", "trimeric glutathione", "glutathione transferases", "providing a", "a chemoprotective", "chemoprotective mechanism", "mechanism against", "against toxicity.", "toxicity. glutathione", "glutathione conjugates", "conjugates are", "are usually", "usually excreted", "excreted as", "as mercapturic", "mercapturic acids", "acids in", "in urine", "guengerich et", "al. 1998", "hamid et", "al. 2013", "2013 .", ". the", "main metabolic", "metabolic routes", "routes of", "of aflatoxin", "aflatoxin in", "in humans", "humans are", "are described", "described here.", "aflatoxins are among", "are among the", "among the principal", "the principal mycotoxins", "principal mycotoxins produced", "mycotoxins produced as", "produced as secondary", "as secondary metabolites", "secondary metabolites by", "metabolites by the", "by the molds", "the molds aspergillus", "molds aspergillus flavus", "aspergillus flavus and", "flavus and aspergillus", "and aspergillus parasiticus", "aspergillus parasiticus that", "parasiticus that contaminate", "that contaminate economically", "contaminate economically important", "economically important food", "important food and", "food and feed", "and feed crops", "crops wild", "wild & turner", "& turner 2002", "turner 2002 .", "2002 . aflatoxin", ". aflatoxin b1", "b1 afb1", "is the most", "the most potent", "most potent naturally", "potent naturally occurring", "naturally occurring carcinogen", "occurring carcinogen known", "carcinogen known and", "known and is", "and is also", "is also an", "also an immunosuppressant.", "an immunosuppressant. it", "immunosuppressant. it is", "it is a", "is a potent", "a potent hepatocarcinogenic", "potent hepatocarcinogenic agent", "hepatocarcinogenic agent in", "agent in many", "in many species", "species and", "and has been", "has been implicated", "been implicated in", "implicated in the", "in the etiology", "the etiology of", "etiology of human", "of human hepatocellular", "human hepatocellular carcinoma.", "hepatocellular carcinoma. poultry", "poultry especially", "turkeys are", "are extremely sensitive", "extremely sensitive to", "sensitive to the", "to the toxic", "the toxic and", "toxic and carcinogenic", "and carcinogenic action", "carcinogenic action of", "action of afb1", "of afb1 present", "afb1 present in", "present in animal", "in animal feed", "feed resulting", "resulting in multi", "in multi million", "multi million dollar", "million dollar losses", "dollar losses to", "losses to the", "to the industry.", "the industry. discerning", "industry. discerning the", "discerning the biochemical", "the biochemical and", "biochemical and molecular", "and molecular mechanisms", "molecular mechanisms of", "mechanisms of this", "of this extreme", "this extreme sensitivity", "extreme sensitivity of", "sensitivity of poultry", "of poultry to", "poultry to afb1", "to afb1 will", "afb1 will help", "will help with", "help with the", "with the development", "the development of", "development of new", "of new strategies", "new strategies to", "strategies to increase", "to increase aflatoxin", "increase aflatoxin resistance", "resistance rawal", "rawal et al.", "et al. 2010", "2010 diaz", "diaz & murcia", "& murcia 2011", "murcia 2011 .


afb1", "2011 .


afb1 has", ".


afb1 has one", "has one major", "one major genotoxic", "major genotoxic metabolic", "genotoxic metabolic fate", "fate conversion", "conversion to afxbo", "afxbo and", "and several others", "several others that", "others that are", "that are less", "are less mutagenic", "less mutagenic but", "mutagenic but that", "but that can", "that can still", "can still be", "still be quite", "be quite toxic.", "quite toxic. afb1", "toxic. afb1 can", "afb1 can be", "can be oxidised", "be oxidised to", "oxidised to the", "the toxic afb1", "toxic afb1 exo", "afb1 exo 8", "exo 8 9", "8 9 epoxide", "epoxide afxbo", "afxbo product", "product by several", "by several cytochrome", "several cytochrome p450", "cytochrome p450 enzymes", "enzymes especially", "especially p450 3a4", "p450 3a4 in", "3a4 in the", "in the liver.", "the liver. this", "liver. this 8", "this 8 9", "9 epoxide can", "epoxide can react", "can react with", "react with the", "with the n7", "the n7 atom", "n7 atom of", "atom of a", "of a guanyl", "a guanyl base", "guanyl base of", "base of dna", "of dna to", "dna to produce", "to produce adducts", "produce adducts by", "adducts by intercalating", "by intercalating between", "intercalating between dna", "between dna base", "dna base pairs.", "base pairs. the", "pairs. the exo", "the exo epoxide", "exo epoxide is", "epoxide is unstable", "is unstable in", "unstable in solution", "solution however", "however and", "and can react", "can react spontaneously", "react spontaneously to", "spontaneously to form", "to form a", "form a diol", "a diol that", "diol that is", "that is no", "is no longer", "no longer reactive", "longer reactive with", "reactive with dna.", "with dna. the", "dna. the diol", "the diol product", "diol product in", "product in turn", "in turn undergoes", "turn undergoes base", "undergoes base catalysed", "base catalysed rearrangement", "catalysed rearrangement to", "rearrangement to a", "to a dialdehyde", "a dialdehyde that", "dialdehyde that can", "that can react", "react with protein", "with protein lysine", "protein lysine residues.", "lysine residues. afb1", "residues. afb1 can", "afb1 can also", "can also be", "also be metabolised", "be metabolised to", "metabolised to products", "products afq1", "afq1 afm1", "afm1 afm1e", "afm1e which", "which have far", "have far less", "far less genotoxic", "less genotoxic consequences", "genotoxic consequences than", "consequences than afb1.", "than afb1. the", "afb1. the main", "the main route", "main route of", "route of detoxification", "of detoxification of", "detoxification of afb1", "of afb1 is", "afb1 is conjugation", "is conjugation of", "conjugation of its", "of its reactive", "its reactive 8", "reactive 8 9", "9 epoxide form", "epoxide form with", "form with glutathione", "glutathione gsh", "gsh . this", ". this reaction", "this reaction is", "reaction is carried", "is carried out", "carried out by", "out by trimeric", "by trimeric glutathione", "trimeric glutathione transferases", "transferases gsts", "providing a chemoprotective", "a chemoprotective mechanism", "chemoprotective mechanism against", "mechanism against toxicity.", "against toxicity. glutathione", "toxicity. glutathione conjugates", "glutathione conjugates are", "conjugates are usually", "are usually excreted", "usually excreted as", "excreted as mercapturic", "as mercapturic acids", "mercapturic acids in", "acids in urine", "urine guengerich", "guengerich et al.", "et al. 1998", "1998 hamid", "hamid et al.", "et al. 2013", "al. 2013 .", "2013 . the", ". the main", "the main metabolic", "main metabolic routes", "metabolic routes of", "routes of aflatoxin", "of aflatoxin in", "aflatoxin in humans", "in humans are", "humans are described", "are described here.", "aflatoxins are among the", "are among the principal", "among the principal mycotoxins", "the principal mycotoxins produced", "principal mycotoxins produced as", "mycotoxins produced as secondary", "produced as secondary metabolites", "as secondary metabolites by", "secondary metabolites by the", "metabolites by the molds", "by the molds aspergillus", "the molds aspergillus flavus", "molds aspergillus flavus and", "aspergillus flavus and aspergillus", "flavus and aspergillus parasiticus", "and aspergillus parasiticus that", "aspergillus parasiticus that contaminate", "parasiticus that contaminate economically", "that contaminate economically important", "contaminate economically important food", "economically important food and", "important food and feed", "food and feed crops", "feed crops wild", "crops wild &", "wild & turner 2002", "& turner 2002 .", "turner 2002 . aflatoxin", "2002 . aflatoxin b1", "aflatoxin b1 afb1", "afb1 is the", "is the most potent", "the most potent naturally", "most potent naturally occurring", "potent naturally occurring carcinogen", "naturally occurring carcinogen known", "occurring carcinogen known and", "carcinogen known and is", "known and is also", "and is also an", "is also an immunosuppressant.", "also an immunosuppressant. it", "an immunosuppressant. it is", "immunosuppressant. it is a", "it is a potent", "is a potent hepatocarcinogenic", "a potent hepatocarcinogenic agent", "potent hepatocarcinogenic agent in", "hepatocarcinogenic agent in many", "agent in many species", "many species and", "species and has", "and has been implicated", "has been implicated in", "been implicated in the", "implicated in the etiology", "in the etiology of", "the etiology of human", "etiology of human hepatocellular", "of human hepatocellular carcinoma.", "human hepatocellular carcinoma. poultry", "carcinoma. poultry especially", "poultry especially turkeys", "especially turkeys are", "turkeys are extremely", "are extremely sensitive to", "extremely sensitive to the", "sensitive to the toxic", "to the toxic and", "the toxic and carcinogenic", "toxic and carcinogenic action", "and carcinogenic action of", "carcinogenic action of afb1", "action of afb1 present", "of afb1 present in", "afb1 present in animal", "present in animal feed", "animal feed resulting", "feed resulting in", "resulting in multi million", "in multi million dollar", "multi million dollar losses", "million dollar losses to", "dollar losses to the", "losses to the industry.", "to the industry. discerning", "the industry. discerning the", "industry. discerning the biochemical", "discerning the biochemical and", "the biochemical and molecular", "biochemical and molecular mechanisms", "and molecular mechanisms of", "molecular mechanisms of this", "mechanisms of this extreme", "of this extreme sensitivity", "this extreme sensitivity of", "extreme sensitivity of poultry", "sensitivity of poultry to", "of poultry to afb1", "poultry to afb1 will", "to afb1 will help", "afb1 will help with", "will help with the", "help with the development", "with the development of", "the development of new", "development of new strategies", "of new strategies to", "new strategies to increase", "strategies to increase aflatoxin", "to increase aflatoxin resistance", "aflatoxin resistance rawal", "resistance rawal et", "rawal et al. 2010", "al. 2010 diaz", "2010 diaz &", "diaz & murcia 2011", "& murcia 2011 .


afb1", "murcia 2011 .


afb1 has", "2011 .


afb1 has one", ".


afb1 has one major", "has one major genotoxic", "one major genotoxic metabolic", "major genotoxic metabolic fate", "metabolic fate conversion", "fate conversion to", "to afxbo and", "afxbo and several", "and several others that", "several others that are", "others that are less", "that are less mutagenic", "are less mutagenic but", "less mutagenic but that", "mutagenic but that can", "but that can still", "that can still be", "can still be quite", "still be quite toxic.", "be quite toxic. afb1", "quite toxic. afb1 can", "toxic. afb1 can be", "afb1 can be oxidised", "can be oxidised to", "be oxidised to the", "oxidised to the toxic", "to the toxic afb1", "the toxic afb1 exo", "toxic afb1 exo 8", "afb1 exo 8 9", "exo 8 9 epoxide", "9 epoxide afxbo", "afxbo product by", "product by several cytochrome", "by several cytochrome p450", "several cytochrome p450 enzymes", "p450 enzymes especially", "enzymes especially p450", "especially p450 3a4 in", "p450 3a4 in the", "3a4 in the liver.", "in the liver. this", "the liver. this 8", "liver. this 8 9", "this 8 9 epoxide", "8 9 epoxide can", "9 epoxide can react", "epoxide can react with", "can react with the", "react with the n7", "with the n7 atom", "the n7 atom of", "n7 atom of a", "atom of a guanyl", "of a guanyl base", "a guanyl base of", "guanyl base of dna", "base of dna to", "of dna to produce", "dna to produce adducts", "to produce adducts by", "produce adducts by intercalating", "adducts by intercalating between", "by intercalating between dna", "intercalating between dna base", "between dna base pairs.", "dna base pairs. the", "base pairs. the exo", "pairs. the exo epoxide", "the exo epoxide is", "exo epoxide is unstable", "epoxide is unstable in", "is unstable in solution", "in solution however", "however and can", "and can react spontaneously", "can react spontaneously to", "react spontaneously to form", "spontaneously to form a", "to form a diol", "form a diol that", "a diol that is", "diol that is no", "that is no longer", "is no longer reactive", "no longer reactive with", "longer reactive with dna.", "reactive with dna. the", "with dna. the diol", "dna. the diol product", "the diol product in", "diol product in turn", "product in turn undergoes", "in turn undergoes base", "turn undergoes base catalysed", "undergoes base catalysed rearrangement", "base catalysed rearrangement to", "catalysed rearrangement to a", "rearrangement to a dialdehyde", "to a dialdehyde that", "a dialdehyde that can", "dialdehyde that can react", "that can react with", "can react with protein", "react with protein lysine", "with protein lysine residues.", "protein lysine residues. afb1", "lysine residues. afb1 can", "residues. afb1 can also", "afb1 can also be", "can also be metabolised", "also be metabolised to", "be metabolised to products", "to products afq1", "afm1e which have", "which have far less", "have far less genotoxic", "far less genotoxic consequences", "less genotoxic consequences than", "genotoxic consequences than afb1.", "consequences than afb1. the", "than afb1. the main", "afb1. the main route", "the main route of", "main route of detoxification", "route of detoxification of", "of detoxification of afb1", "detoxification of afb1 is", "of afb1 is conjugation", "afb1 is conjugation of", "is conjugation of its", "conjugation of its reactive", "of its reactive 8", "its reactive 8 9", "reactive 8 9 epoxide", "8 9 epoxide form", "9 epoxide form with", "epoxide form with glutathione", "with glutathione gsh", "glutathione gsh .", "gsh . this reaction", ". this reaction is", "this reaction is carried", "reaction is carried out", "is carried out by", "carried out by trimeric", "out by trimeric glutathione", "by trimeric glutathione transferases", "glutathione transferases gsts", "gsts providing", "providing a chemoprotective mechanism", "a chemoprotective mechanism against", "chemoprotective mechanism against toxicity.", "mechanism against toxicity. glutathione", "against toxicity. glutathione conjugates", "toxicity. glutathione conjugates are", "glutathione conjugates are usually", "conjugates are usually excreted", "are usually excreted as", "usually excreted as mercapturic", "excreted as mercapturic acids", "as mercapturic acids in", "mercapturic acids in urine", "in urine guengerich", "urine guengerich et", "guengerich et al. 1998", "al. 1998 hamid", "1998 hamid et", "hamid et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the main", ". the main metabolic", "the main metabolic routes", "main metabolic routes of", "metabolic routes of aflatoxin", "routes of aflatoxin in", "of aflatoxin in humans", "aflatoxin in humans are", "in humans are described", "humans are described here.", "aflatoxins are among the principal", "are among the principal mycotoxins", "among the principal mycotoxins produced", "the principal mycotoxins produced as", "principal mycotoxins produced as secondary", "mycotoxins produced as secondary metabolites", "produced as secondary metabolites by", "as secondary metabolites by the", "secondary metabolites by the molds", "metabolites by the molds aspergillus", "by the molds aspergillus flavus", "the molds aspergillus flavus and", "molds aspergillus flavus and aspergillus", "aspergillus flavus and aspergillus parasiticus", "flavus and aspergillus parasiticus that", "and aspergillus parasiticus that contaminate", "aspergillus parasiticus that contaminate economically", "parasiticus that contaminate economically important", "that contaminate economically important food", "contaminate economically important food and", "economically important food and feed", "important food and feed crops", "and feed crops wild", "feed crops wild &", "crops wild & turner", "wild & turner 2002 .", "& turner 2002 . aflatoxin", "turner 2002 . aflatoxin b1", ". aflatoxin b1 afb1", "b1 afb1 is", "afb1 is the most", "is the most potent naturally", "the most potent naturally occurring", "most potent naturally occurring carcinogen", "potent naturally occurring carcinogen known", "naturally occurring carcinogen known and", "occurring carcinogen known and is", "carcinogen known and is also", "known and is also an", "and is also an immunosuppressant.", "is also an immunosuppressant. it", "also an immunosuppressant. it is", "an immunosuppressant. it is a", "immunosuppressant. it is a potent", "it is a potent hepatocarcinogenic", "is a potent hepatocarcinogenic agent", "a potent hepatocarcinogenic agent in", "potent hepatocarcinogenic agent in many", "hepatocarcinogenic agent in many species", "in many species and", "many species and has", "species and has been", "and has been implicated in", "has been implicated in the", "been implicated in the etiology", "implicated in the etiology of", "in the etiology of human", "the etiology of human hepatocellular", "etiology of human hepatocellular carcinoma.", "of human hepatocellular carcinoma. poultry", "hepatocellular carcinoma. poultry especially", "carcinoma. poultry especially turkeys", "especially turkeys are extremely", "turkeys are extremely sensitive", "are extremely sensitive to the", "extremely sensitive to the toxic", "sensitive to the toxic and", "to the toxic and carcinogenic", "the toxic and carcinogenic action", "toxic and carcinogenic action of", "and carcinogenic action of afb1", "carcinogenic action of afb1 present", "action of afb1 present in", "of afb1 present in animal", "afb1 present in animal feed", "in animal feed resulting", "animal feed resulting in", "feed resulting in multi", "resulting in multi million dollar", "in multi million dollar losses", "multi million dollar losses to", "million dollar losses to the", "dollar losses to the industry.", "losses to the industry. discerning", "to the industry. discerning the", "the industry. discerning the biochemical", "industry. discerning the biochemical and", "discerning the biochemical and molecular", "the biochemical and molecular mechanisms", "biochemical and molecular mechanisms of", "and molecular mechanisms of this", "molecular mechanisms of this extreme", "mechanisms of this extreme sensitivity", "of this extreme sensitivity of", "this extreme sensitivity of poultry", "extreme sensitivity of poultry to", "sensitivity of poultry to afb1", "of poultry to afb1 will", "poultry to afb1 will help", "to afb1 will help with", "afb1 will help with the", "will help with the development", "help with the development of", "with the development of new", "the development of new strategies", "development of new strategies to", "of new strategies to increase", "new strategies to increase aflatoxin", "strategies to increase aflatoxin resistance", "increase aflatoxin resistance rawal", "aflatoxin resistance rawal et", "resistance rawal et al.", "et al. 2010 diaz", "al. 2010 diaz &", "2010 diaz & murcia", "diaz & murcia 2011 .


afb1", "& murcia 2011 .


afb1 has", "murcia 2011 .


afb1 has one", "2011 .


afb1 has one major", ".


afb1 has one major genotoxic", "has one major genotoxic metabolic", "one major genotoxic metabolic fate", "genotoxic metabolic fate conversion", "metabolic fate conversion to", "fate conversion to afxbo", "conversion to afxbo and", "to afxbo and several", "afxbo and several others", "and several others that are", "several others that are less", "others that are less mutagenic", "that are less mutagenic but", "are less mutagenic but that", "less mutagenic but that can", "mutagenic but that can still", "but that can still be", "that can still be quite", "can still be quite toxic.", "still be quite toxic. afb1", "be quite toxic. afb1 can", "quite toxic. afb1 can be", "toxic. afb1 can be oxidised", "afb1 can be oxidised to", "can be oxidised to the", "be oxidised to the toxic", "oxidised to the toxic afb1", "to the toxic afb1 exo", "the toxic afb1 exo 8", "toxic afb1 exo 8 9", "afb1 exo 8 9 epoxide", "8 9 epoxide afxbo", "epoxide afxbo product", "afxbo product by several", "product by several cytochrome p450", "by several cytochrome p450 enzymes", "cytochrome p450 enzymes especially", "p450 enzymes especially p450", "enzymes especially p450 3a4", "especially p450 3a4 in the", "p450 3a4 in the liver.", "3a4 in the liver. this", "in the liver. this 8", "the liver. this 8 9", "liver. this 8 9 epoxide", "this 8 9 epoxide can", "8 9 epoxide can react", "9 epoxide can react with", "epoxide can react with the", "can react with the n7", "react with the n7 atom", "with the n7 atom of", "the n7 atom of a", "n7 atom of a guanyl", "atom of a guanyl base", "of a guanyl base of", "a guanyl base of dna", "guanyl base of dna to", "base of dna to produce", "of dna to produce adducts", "dna to produce adducts by", "to produce adducts by intercalating", "produce adducts by intercalating between", "adducts by intercalating between dna", "by intercalating between dna base", "intercalating between dna base pairs.", "between dna base pairs. the", "dna base pairs. the exo", "base pairs. the exo epoxide", "pairs. the exo epoxide is", "the exo epoxide is unstable", "exo epoxide is unstable in", "epoxide is unstable in solution", "unstable in solution however", "solution however and", "however and can react", "and can react spontaneously to", "can react spontaneously to form", "react spontaneously to form a", "spontaneously to form a diol", "to form a diol that", "form a diol that is", "a diol that is no", "diol that is no longer", "that is no longer reactive", "is no longer reactive with", "no longer reactive with dna.", "longer reactive with dna. the", "reactive with dna. the diol", "with dna. the diol product", "dna. the diol product in", "the diol product in turn", "diol product in turn undergoes", "product in turn undergoes base", "in turn undergoes base catalysed", "turn undergoes base catalysed rearrangement", "undergoes base catalysed rearrangement to", "base catalysed rearrangement to a", "catalysed rearrangement to a dialdehyde", "rearrangement to a dialdehyde that", "to a dialdehyde that can", "a dialdehyde that can react", "dialdehyde that can react with", "that can react with protein", "can react with protein lysine", "react with protein lysine residues.", "with protein lysine residues. afb1", "protein lysine residues. afb1 can", "lysine residues. afb1 can also", "residues. afb1 can also be", "afb1 can also be metabolised", "can also be metabolised to", "also be metabolised to products", "metabolised to products afq1", "products afq1 afm1", "afq1 afm1 afm1e", "afm1 afm1e which", "afm1e which have far", "which have far less genotoxic", "have far less genotoxic consequences", "far less genotoxic consequences than", "less genotoxic consequences than afb1.", "genotoxic consequences than afb1. the", "consequences than afb1. the main", "than afb1. the main route", "afb1. the main route of", "the main route of detoxification", "main route of detoxification of", "route of detoxification of afb1", "of detoxification of afb1 is", "detoxification of afb1 is conjugation", "of afb1 is conjugation of", "afb1 is conjugation of its", "is conjugation of its reactive", "conjugation of its reactive 8", "of its reactive 8 9", "its reactive 8 9 epoxide", "reactive 8 9 epoxide form", "8 9 epoxide form with", "9 epoxide form with glutathione", "form with glutathione gsh", "with glutathione gsh .", "glutathione gsh . this", "gsh . this reaction is", ". this reaction is carried", "this reaction is carried out", "reaction is carried out by", "is carried out by trimeric", "carried out by trimeric glutathione", "out by trimeric glutathione transferases", "trimeric glutathione transferases gsts", "gsts providing a", "providing a chemoprotective mechanism against", "a chemoprotective mechanism against toxicity.", "chemoprotective mechanism against toxicity. glutathione", "mechanism against toxicity. glutathione conjugates", "against toxicity. glutathione conjugates are", "toxicity. glutathione conjugates are usually", "glutathione conjugates are usually excreted", "conjugates are usually excreted as", "are usually excreted as mercapturic", "usually excreted as mercapturic acids", "excreted as mercapturic acids in", "as mercapturic acids in urine", "acids in urine guengerich", "in urine guengerich et", "urine guengerich et al.", "et al. 1998 hamid", "al. 1998 hamid et", "1998 hamid et al.", "hamid et al. 2013 .", "et al. 2013 . the", "al. 2013 . the main", "2013 . the main metabolic", ". the main metabolic routes", "the main metabolic routes of", "main metabolic routes of aflatoxin", "metabolic routes of aflatoxin in", "routes of aflatoxin in humans", "of aflatoxin in humans are", "aflatoxin in humans are described", "in humans are described here." ] }, { "record_id": "GLY_000594_1_430", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5467337", "r hsa", "hsa 5467337", "r hsa 5467337" ] }, { "record_id": "GLY_000594_1_430", "filename": "human_protein_pathways_reactome", 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"al. 2005 suzuki", "2005 suzuki et", "suzuki et al. 2005", "al. 2005 kim", "2005 kim et", "kim et al. 2006", "al. 2006 weinberg", "2006 weinberg et", "weinberg et al. 2006", "al. 2006 kim", "2006 kim et", "kim et al. 2008", "al. 2008 reviewed", "2008 reviewed in", "morris 2010 li", "2010 li et", "li et al. 2014", "2014 rnaa", "rnaa is associated with", "with methylation of histone", "h3 at lysine 4", "lysine 4 huang", "4 huang et", "huang et al. 2012", "al. 2012 reviewed", "2012 reviewed in", "reviewed in li et", "in li et al.", "al. 2014 . small", "2014 . small rnas", ". small rnas in", "small rnas in the", "rnas in the nucleus", "in the nucleus have", "the nucleus have also", "nucleus have also been", "have also been shown", "also been shown to", "been shown to play", "shown to play roles", "to play roles in", "play roles in alternative", "roles in alternative splicing", "alternative splicing liu", "splicing liu et", "2012 ameyar zazoua", "ameyar zazoua et al.", "2012 and dna", "and dna damage repair", "damage repair wei", "wei et al.", "2012 francia et", "al. 2012 .", ". nevertheless elucidation", "nevertheless elucidation of", "elucidation of the detailed", "of the detailed mechanisms", "the detailed mechanisms of", "detailed mechanisms of small", "mechanisms of small rna", "of small rna action", "small rna action requires", "rna action requires further", "action requires further research.", "recent evidence indicates that small", "evidence indicates that small rnas", "indicates that small rnas participate", "that small rnas participate in", "small rnas participate in transcriptional", "rnas participate in transcriptional regulation", "participate in transcriptional regulation in", "in transcriptional regulation in addition", "transcriptional regulation in addition to", "regulation in addition to post", "in addition to post transcriptional", "addition to post transcriptional silencing.", "to post transcriptional silencing. components", "post transcriptional silencing. components of", "transcriptional silencing. components of the", "silencing. components of the rnai", "components of the rnai machinery", "the rnai machinery argonaute1", "machinery argonaute1 ago1", "argonaute1 ago1 eif2c1", "and dicer are observed", "dicer are observed associated", "are observed associated with micrornas", "associated with micrornas mirnas", "micrornas mirnas in", "mirnas in both the", "in both the cytosol and", "both the cytosol and the", "the cytosol and the nucleus", "and the nucleus robb", "the nucleus robb et", "nucleus robb et al.", "et al. 2005 weinmann", "al. 2005 weinmann et", "2005 weinmann et al.", "et al. 2009 doyle", "al. 2009 doyle et", "2009 doyle et al.", "et al. 2013 nishi", "al. 2013 nishi et", "2013 nishi et al.", "et al. 2013 gagnon", "al. 2013 gagnon et", "2013 gagnon et al.", "gagnon et al. 2014 .", "et al. 2014 . the", "al. 2014 . the ago:mirna", "2014 . the ago:mirna complexes", ". the ago:mirna complexes are", "the ago:mirna complexes are imported", "ago:mirna complexes are imported into", "complexes are imported into the", "are imported into the nucleus", "imported into the nucleus by", "into the nucleus by importin", "the nucleus by importin 8", "by importin 8 ipo8", "8 ipo8 imp8", "ipo8 imp8 ranbp8", "imp8 ranbp8 and", "ranbp8 and also by", "and also by an unknown", "also by an unknown importin", "by an unknown importin while", "an unknown importin while associated", "unknown importin while associated with", "importin while associated with the", "while associated with the nuclear", "associated with the nuclear shuttling", "with the nuclear shuttling protein", "the nuclear shuttling protein tnrc6a", "shuttling protein tnrc6a reviewed", "protein tnrc6a reviewed in", "tnrc6a reviewed in schraivogel", "reviewed in schraivogel and meister", "in schraivogel and meister 2014", "schraivogel and meister 2014 .
within", "and meister 2014 .
within the", "meister 2014 .
within the nucleus", ".
within the nucleus ago2", "nucleus ago2 tnrc6a", "ago2 tnrc6a and", "tnrc6a and dicer may", "and dicer may associate in", "dicer may associate in a", "may associate in a complex", "in a complex gagnon", "a complex gagnon et", "complex gagnon et al.", "et al. 2014 . nuclear", "al. 2014 . nuclear ago1", "2014 . nuclear ago1 and", ". nuclear ago1 and ago2", "nuclear ago1 and ago2 in", "ago1 and ago2 in complexes", "and ago2 in complexes with", "ago2 in complexes with small", "in complexes with small rnas", "complexes with small rnas are", "with small rnas are observed", "small rnas are observed to", "rnas are observed to activate", "are observed to activate transcription", "to activate transcription rna", "activate transcription rna activation", "activation rnaa or", "rnaa or repress transcription", "or repress transcription transcriptional", "repress transcription transcriptional gene", "transcription transcriptional gene silencing", "transcriptional gene silencing tgs", "silencing tgs of", "tgs of genes that", "of genes that contain sequences", "genes that contain sequences matching", "that contain sequences matching the", "contain sequences matching the small", "sequences matching the small rnas", "the small rnas reviewed", "small rnas reviewed in", "rnas reviewed in malecova", "reviewed in malecova and morris", "in malecova and morris 2010", "and morris 2010 huang", "morris 2010 huang and", "2010 huang and li", "and li 2012 gagnon", "li 2012 gagnon and", "2012 gagnon and corey", "and corey 2012 huang", "corey 2012 huang and", "2012 huang and li", "and li 2014 salmanidis", "li 2014 salmanidis et", "2014 salmanidis et al.", "et al. 2014 stroynowska", "al. 2014 stroynowska czerwinska", "2014 stroynowska czerwinska et", "stroynowska czerwinska et al. 2014", "czerwinska et al. 2014 .", "et al. 2014 . tgs", "al. 2014 . tgs is", "2014 . tgs is associated", ". tgs is associated with", "tgs is associated with methylation", "is associated with methylation of", "associated with methylation of cytosine", "with methylation of cytosine in", "methylation of cytosine in dna", "of cytosine in dna and", "cytosine in dna and methylation", "in dna and methylation of", "dna and methylation of histone", "and methylation of histone h3", "methylation of histone h3 at", "of histone h3 at lysine", "histone h3 at lysine 9", "h3 at lysine 9 and", "at lysine 9 and lysine", "lysine 9 and lysine 27", "and lysine 27 castanotto", "lysine 27 castanotto et", "27 castanotto et al.", "et al. 2005 suzuki", "al. 2005 suzuki et", "2005 suzuki et al.", "et al. 2005 kim", "al. 2005 kim et", "2005 kim et al.", "et al. 2006 weinberg", "al. 2006 weinberg et", "2006 weinberg et al.", "et al. 2006 kim", "al. 2006 kim et", "2006 kim et al.", "et al. 2008 reviewed", "al. 2008 reviewed in", "2008 reviewed in malecova", "and morris 2010 li", "morris 2010 li et", "2010 li et al.", "al. 2014 rnaa", "2014 rnaa is", "rnaa is associated with methylation", "associated with methylation of histone", "with methylation of histone h3", "histone h3 at lysine 4", "at lysine 4 huang", "lysine 4 huang et", "4 huang et al.", "et al. 2012 reviewed", "al. 2012 reviewed in", "2012 reviewed in li", "reviewed in li et al.", "in li et al. 2014", "li et al. 2014 .", "et al. 2014 . small", "al. 2014 . small rnas", "2014 . small rnas in", ". small rnas in the", "small rnas in the nucleus", "rnas in the nucleus have", "in the nucleus have also", "the nucleus have also been", "nucleus have also been shown", "have also been shown to", "also been shown to play", "been shown to play roles", "shown to play roles in", "to play roles in alternative", "play roles in alternative splicing", "in alternative splicing liu", "alternative splicing liu et", "splicing liu et al.", "liu et al. 2012", "al. 2012 ameyar", "2012 ameyar zazoua et", "zazoua et al. 2012", "al. 2012 and", "2012 and dna damage", "dna damage repair wei", "repair wei et", "al. 2012 francia", "2012 francia et al.", "francia et al. 2012", "et al. 2012 .", "al. 2012 . nevertheless", "2012 . nevertheless elucidation", ". nevertheless elucidation of", "nevertheless elucidation of the", "elucidation of the detailed mechanisms", "of the detailed mechanisms of", "the detailed mechanisms of small", "detailed mechanisms of small rna", "mechanisms of small rna action", "of small rna action requires", "small rna action requires further", "rna action requires further research." ] }, { "record_id": "GLY_000594_1_438", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5578775", "r hsa", "hsa 5578775", "r hsa 5578775" ] }, { "record_id": "GLY_000594_1_438", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ion homeostasis", "ion channels", "channels and", "and ion", "homeostasis in", "in relation", "relation to", "to cardiac", "cardiac conduction", "conduction is", "is described", "described in", "in this", "this section", "couette et", "et al.", 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importantly", "importantly blood", "blood cells in", "cells in the", "in the periphery", "the periphery produce", "periphery produce normal", "produce normal amounts", "normal amounts of", "amounts of interferons", "interferons even", "even in tlr3", "in tlr3 deficient", "tlr3 deficient patients", "patients which", "which perhaps can", "perhaps can be", "can be explained", "be explained by", "explained by rigi", "by rigi or", "rigi or mda5", "or mda5 mediated", "mda5 mediated antiviral", "mediated antiviral responses.", "toll like receptor 3", "receptor 3 tlr3", "tlr3 recognizes double", "recognizes double stranded rna", "stranded rna dsrna", "dsrna an", "an intermediate product during", "intermediate product during viral", "product during viral replication", "during viral replication for", "viral replication for most", "replication for most viruses.", "for most viruses. tlr3", "most viruses. tlr3 is", "viruses. tlr3 is expressed", "tlr3 is expressed in", "is expressed in various", 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.", "al. 2012 . children", "2012 . children with", ". children with inborn", "children with inborn errors", "with inborn errors of", "inborn errors of tlr3", "errors of tlr3 mediated", "of tlr3 mediated immunity", "tlr3 mediated immunity are", "mediated immunity are prone", "immunity are prone to", "are prone to hsv", "prone to hsv 1", "to hsv 1 encephalitis", "1 encephalitis hse", "hse a", "a rare life threatening", "rare life threatening complication", "life threatening complication during", "threatening complication during hsv", "complication during hsv 1", "during hsv 1 infection", "1 infection casrouge", "infection casrouge a", "casrouge a et al.", "a et al. 2006", "al. 2006 perez", "2006 perez de", "perez de diego r", "de diego r et", "diego r et al.", "r et al. 2010", "al. 2010 zhang", "2010 zhang sy", "zhang sy et al.", "sy et al. 2007", "al. 2007 herman", "2007 herman m", "herman m et al.", "m et al. 2012", "al. 2012 lafaille", "2012 lafaille fg", "al. 2012 . the", "2012 . the 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lafaille", "2011 lafaille fg", "al. 2012 . importantly", ". importantly blood", "importantly blood cells", "blood cells in the", "cells in the periphery", "in the periphery produce", "the periphery produce normal", "periphery produce normal amounts", "produce normal amounts of", "normal amounts of interferons", "of interferons even", "interferons even in", "even in tlr3 deficient", "in tlr3 deficient patients", "deficient patients which", "patients which perhaps", "which perhaps can be", "perhaps can be explained", "can be explained by", "be explained by rigi", "explained by rigi or", "by rigi or mda5", "rigi or mda5 mediated", "or mda5 mediated antiviral", "mda5 mediated antiviral responses.", "like receptor 3 tlr3", "3 tlr3 recognizes", "tlr3 recognizes double stranded", "double stranded rna dsrna", "dsrna an intermediate", "an intermediate product during viral", "intermediate product during viral replication", "product during viral replication for", "during viral replication for 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importantly blood cells", "importantly blood cells in", "blood cells in the periphery", "cells in the periphery produce", "in the periphery produce normal", "the periphery produce normal amounts", "periphery produce normal amounts of", "produce normal amounts of interferons", "amounts of interferons even", "of interferons even in", "interferons even in tlr3", "even in tlr3 deficient patients", "tlr3 deficient patients which", "deficient patients which perhaps", "patients which perhaps can", "which perhaps can be explained", "perhaps can be explained by", "can be explained by rigi", "be explained by rigi or", "explained by rigi or mda5", "by rigi or mda5 mediated", "rigi or mda5 mediated antiviral", "or mda5 mediated antiviral responses." ] }, { "record_id": "GLY_000594_1_441", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5602415", "r hsa", "hsa 5602415", "r hsa 5602415" ] }, { "record_id": "GLY_000594_1_441", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "unc93b1 deficiency", "deficiency hse", "unc93b1 deficiency hse", "unc93b1 is", "is an", "an endoplasmic", "endoplasmic reticulum", "reticulum protein", "protein with", "with 12", "12 membrane", "membrane spanning", "spanning domains.", "domains. signaling", "signaling cascades", "cascades of", "of nucleotide", "nucleotide sensing", "sensing endosomal", "endosomal toll", "toll like", "like receptors", "tlr3 and", "and tlr7", "tlr7 9", "depends on", "on functional", "functional unc93b1", "which is", "is thought", "thought to", "to deliver", "deliver these", "these tlrs", "tlrs from", "from the", "the er", "er to", "to the", "the endosome", "endosome where", "where they", "they recognize", "recognize specific", "specific pathogenic", "pathogenic patterns", "patterns and", "and initiate", "initiate host", "host immune", "immune responses.

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defective", ".

defective unc93b1", "unc93b1 also", "also impairs", "impairs the", "the tlr7", "tlr8 and", "and tlr9", "tlr9 signaling", "signaling pathways.", "pathways. peripheral", "peripheral blood", "mononuclear cells", "from unc93b", "unc93b deficient", "deficient patients", "patients did", "did not", "not respond", "respond to", "the stimulation", "stimulation of", "of tlr7", "or tlr9", "in terms", "terms of", "the production", "of type", "iii interferons", "and other", "other cytokines", "cytokines tested", ". moreover", "no inducible", "inducible cd62l", "cd62l shedding", "shedding on", "on granulocytes", "granulocytes was", "was detected", "detected after", "after stimulation", "of whole", "whole blood", "blood cells", "cells derived", "unc93b deficients", "deficients patients", "with r", "r 848", "agonist of", "tlr7 and", "and tlr8", "von bernuth", "bernuth h.", "h. et", "al. 2008", "2008 .", "no clinical", "clinical condition", "condition has", "been so", "so far", "far associated", "associated with", "with impaired", "impaired tlr7", "tlr9 due", "due to", "to unc93b1", "deficiency so", "so this", "this defect", "defect is", "is not", "not annotated", "annotated here.", "unc93b1 is an", "is an endoplasmic", "an endoplasmic reticulum", "endoplasmic reticulum protein", "reticulum protein with", "protein with 12", "with 12 membrane", "12 membrane spanning", "membrane spanning domains.", "spanning domains. signaling", "domains. signaling cascades", "signaling cascades of", "cascades of nucleotide", "of nucleotide sensing", "nucleotide sensing endosomal", "sensing endosomal toll", "endosomal toll like", "toll like receptors", "receptors tlr3", "tlr3 and tlr7", "and tlr7 9", "9 depends", "depends on functional", "on functional unc93b1", "unc93b1 which", "which is thought", "is thought to", "thought to deliver", "to deliver these", "deliver these tlrs", "these tlrs from", "tlrs from the", "from the er", "the er to", "er to the", "to the endosome", "the endosome where", "endosome where they", "where they recognize", "they recognize specific", "recognize specific pathogenic", "specific pathogenic patterns", "pathogenic patterns and", "patterns and initiate", "and initiate host", "initiate host immune", "host immune responses.

unc93b", "immune responses.

unc93b deficiency", "responses.

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defective", "2012 .

defective unc93b1", ".

defective unc93b1 also", "unc93b1 also impairs", "also impairs the", "impairs the tlr7", "tlr7 tlr8", "tlr8 and tlr9", "and tlr9 signaling", "tlr9 signaling pathways.", "signaling pathways. peripheral", "pathways. peripheral blood", "blood mononuclear", "cells pbmcs", "pbmcs from", "from unc93b deficient", "unc93b deficient patients", "deficient patients did", "patients did not", "did not respond", "not respond to", "respond to the", "to the stimulation", "the stimulation of", "stimulation of tlr7", "tlr8 or", "tlr9 in", "in terms of", "terms of the", "of the production", "the production of", "production of type", "of type i", "and iii interferons", "interferons and", "and other cytokines", "other cytokines tested", "tested casrouge", "2006 . moreover", "moreover no", "no inducible cd62l", "inducible cd62l shedding", "cd62l shedding on", "shedding on granulocytes", "on granulocytes was", "granulocytes was detected", "was detected after", "detected after stimulation", "after stimulation of", "stimulation of whole", "of whole blood", "whole blood cells", "blood cells derived", "cells derived from", "derived from unc93b", "from unc93b deficients", "unc93b deficients patients", "deficients patients with", "patients with r", "with r 848", "848 agonist", "agonist of tlr7", "of tlr7 and", "tlr7 and tlr8", "von bernuth h.", "bernuth h. et", "h. et al.", "et al. 2008", "al. 2008 .", "2008 . however", "however no", "no clinical condition", "clinical condition has", "condition has been", "has been so", "been so far", "so far associated", "far associated with", "associated with impaired", "with impaired tlr7", "tlr8 tlr9", "tlr9 due to", "due to unc93b1", "to unc93b1 deficiency", "unc93b1 deficiency so", "deficiency so this", "so this defect", "this defect is", "defect is not", "is not annotated", "not annotated here.", "unc93b1 is an endoplasmic", "is an endoplasmic reticulum", "an endoplasmic reticulum protein", "endoplasmic reticulum protein with", "reticulum protein with 12", "protein with 12 membrane", "with 12 membrane spanning", "12 membrane spanning domains.", "membrane spanning domains. signaling", "spanning domains. signaling cascades", "domains. signaling cascades of", "signaling cascades of nucleotide", "cascades of nucleotide sensing", "of nucleotide sensing endosomal", "nucleotide sensing endosomal toll", "sensing endosomal toll like", "endosomal toll like receptors", "like receptors tlr3", "receptors tlr3 and", "tlr3 and tlr7 9", "tlr7 9 depends", "9 depends on", "depends on functional unc93b1", "functional unc93b1 which", "unc93b1 which is", "which is thought to", "is thought to deliver", "thought to deliver these", "to deliver these tlrs", "deliver these tlrs from", "these tlrs from the", "tlrs from the er", "from the er to", "the er to the", "er to the endosome", "to the endosome where", "the endosome where they", "endosome where they recognize", "where they recognize specific", "they recognize specific pathogenic", "recognize specific pathogenic patterns", "specific pathogenic patterns and", "pathogenic patterns and initiate", "patterns and initiate host", "and initiate host immune", "initiate host immune responses.

unc93b", "host immune responses.

unc93b deficiency", "immune responses.

unc93b deficiency has", "responses.

unc93b deficiency has been", "deficiency has been implicated", "has been implicated in", "been implicated in the", "implicated in the increased", "in the increased susceptibility", "the increased susceptibility to", "increased susceptibility to herpes", "susceptibility to herpes simplex", "to herpes simplex virus", "herpes simplex virus type", "simplex virus type 1", "type 1 hsv1", "hse a", "a rare complication during", "rare complication during hsv", "complication during hsv 1", "during hsv 1 infection", "hsv 1 infection of", "1 infection of the", "infection of the central", "of the central nervous", "the central nervous system", "nervous system cns", "cns casrouge", "casrouge a et al.", "a et al. 2006", "et al. 2006 .", "al. 2006 . patients", "2006 . patients derived", ". patients derived unc96b1", "patients derived unc96b1 deficient", "derived unc96b1 deficient fibroblasts", "unc96b1 deficient fibroblasts showed", "deficient fibroblasts showed an", "fibroblasts showed an impaired", "showed an impaired production", "an impaired production of", "impaired production of ifn", "production of ifn beta", "of ifn beta and", "and gamma following", "gamma following stimulation with", "following stimulation with tlr3", "stimulation with tlr3 agonist", "with tlr3 agonist poly", "tlr3 agonist poly i:c", "i:c casrouge", "al. 2006 . these", "2006 . these cells", ". these cells were", "these cells were also", "cells were also more", "were also more susceptible", "also more susceptible to", "more susceptible to hsv1", "susceptible to hsv1 infection", "hsv1 infection showing", "infection showing rapid", "showing rapid viral replication", "rapid viral replication together", "viral replication together with", "replication together with high", "together with high mortality", "with high mortality rates.", "high mortality rates. furthermore", "rates. furthermore pluripotent", "furthermore pluripotent stem", "stem cells ipsc", "ipsc derived from", "derived from hse patient", "from hse patient dermal", "hse patient dermal fibroblasts", "patient dermal fibroblasts were", "dermal fibroblasts were differentiated", "fibroblasts were differentiated into", "were differentiated into populations", "differentiated into populations of", "into populations of neural", "populations of neural stem", "of neural stem cells", "stem cells nsc", "nsc neurons", "neurons astrocytes and", "and oligodendrocytes lafaille", "oligodendrocytes lafaille fg", "lafaille fg et al.", "fg et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the impaired", ". the impaired induction", "the impaired induction of", "impaired induction of ifn", "induction of ifn beta", "ifn beta and gamma", "beta and gamma was", "and gamma was observed", "gamma was observed in", "was observed in all", "observed in all tested", "in all tested cns", "all tested cns cells", "tested cns cells upon", "cns cells upon stimulation", "cells upon stimulation with", "upon stimulation with poly", "stimulation with poly i:c", "with poly i:c .", "poly i:c . however", ". however hsv1", "however hsv1 infection", "hsv1 infection selectively affected", "infection selectively affected type", "selectively affected type i", "affected type i and", "type i and iii", "i and iii ifn", "and iii ifn production", "iii ifn production in", "ifn production in unc93b1", "production in unc93b1 deficient", "in unc93b1 deficient neurons", "unc93b1 deficient neurons and", "deficient neurons and oligodendrocytes", "al. 2012 . thus", ". thus impaired", "thus impaired tlr3", "impaired tlr3 mediated unc93b", "tlr3 mediated unc93b dependent", "mediated unc93b dependent type", "unc93b dependent type i", "dependent type i and", "ifn production in respose", "production in respose to", "in respose to hsv1", "respose to hsv1 infection", "to hsv1 infection in", "hsv1 infection in cns", "in cns in", "cns in neurons", "in neurons and oligodendrocytes", "neurons and oligodendrocytes in", "and oligodendrocytes in particular", "in particular may", "particular may underline", "may underline the pathogenesis", "underline the pathogenesis of", "the pathogenesis of hse", "pathogenesis of hse in", "of hse in patients", "hse in patients with", "in patients with unc93b1", "patients with unc93b1 deficiency", "unc93b1 deficiency casrouge", "deficiency casrouge a", "al. 2006 lafaille", "2006 lafaille fg", "et al. 2012 .

defective", "al. 2012 .

defective unc93b1", "2012 .

defective unc93b1 also", ".

defective unc93b1 also impairs", "unc93b1 also impairs the", "also impairs the tlr7", "the tlr7 tlr8", "tlr7 tlr8 and", "tlr8 and tlr9 signaling", "and tlr9 signaling pathways.", "tlr9 signaling pathways. peripheral", "signaling pathways. peripheral blood", "peripheral blood mononuclear", "blood mononuclear cells", "mononuclear cells pbmcs", "pbmcs from unc93b", "from unc93b deficient patients", "unc93b deficient patients did", "deficient patients did not", "patients did not respond", "did not respond to", "not respond to the", "respond to the stimulation", "to the stimulation of", "the stimulation of tlr7", "of tlr7 tlr8", "tlr8 or tlr9", "or tlr9 in", "tlr9 in terms", "in terms of the", "terms of the production", "of the production of", "the production of type", "production of type i", "of type i and", "i and iii interferons", "iii interferons and", "interferons and other", "and other cytokines tested", "cytokines tested casrouge", "tested casrouge a", "al. 2006 . moreover", ". moreover no", "moreover no inducible", "no inducible cd62l shedding", "inducible cd62l shedding on", "cd62l shedding on granulocytes", "shedding on granulocytes was", "on granulocytes was detected", "granulocytes was detected after", "was detected after stimulation", "detected after stimulation of", "after stimulation of whole", "stimulation of whole blood", "of whole blood cells", "whole blood cells derived", "blood cells derived from", "cells derived from unc93b", "derived from unc93b deficients", "from unc93b deficients patients", "unc93b deficients patients with", "deficients patients with r", "patients with r 848", "r 848 agonist", "848 agonist of", "agonist of tlr7 and", "of tlr7 and tlr8", "tlr8 von", "von bernuth h. et", "bernuth h. et al.", "h. et al. 2008", "et al. 2008 .", "al. 2008 . however", ". however no", "however no clinical", "no clinical condition has", "clinical condition has been", "condition has been so", "has been so far", "been so far associated", "so far associated with", "far associated with impaired", "associated with impaired tlr7", "impaired tlr7 tlr8", "tlr8 tlr9 due", "tlr9 due to unc93b1", "due to unc93b1 deficiency", "to unc93b1 deficiency so", "unc93b1 deficiency so this", "deficiency so this defect", "so this defect is", "this defect is not", "defect is not annotated", "is not annotated here.", "unc93b1 is an endoplasmic reticulum", "is an endoplasmic reticulum protein", "an endoplasmic reticulum protein with", "endoplasmic reticulum protein with 12", "reticulum protein with 12 membrane", "protein with 12 membrane spanning", "with 12 membrane spanning domains.", "12 membrane spanning domains. signaling", "membrane spanning domains. signaling cascades", "spanning domains. signaling cascades of", "domains. signaling cascades of nucleotide", "signaling cascades of nucleotide sensing", "cascades of nucleotide sensing endosomal", "of nucleotide sensing endosomal toll", "nucleotide sensing endosomal toll like", "sensing endosomal toll like receptors", "toll like receptors tlr3", "like receptors tlr3 and", "receptors tlr3 and tlr7", "and tlr7 9 depends", "tlr7 9 depends on", "9 depends on functional", "on functional unc93b1 which", "functional unc93b1 which is", "unc93b1 which is thought", "which is thought to deliver", "is thought to deliver these", "thought to deliver these tlrs", "to deliver these tlrs from", "deliver these tlrs from the", "these tlrs from the er", "tlrs from the er to", "from the er to the", "the er to the endosome", "er to the endosome where", "to the endosome where they", "the endosome where they recognize", "endosome where they recognize specific", "where they recognize specific pathogenic", "they recognize specific pathogenic patterns", "recognize specific pathogenic patterns and", "specific pathogenic patterns and initiate", "pathogenic patterns and initiate host", "patterns and initiate host immune", "and initiate host immune responses.

unc93b", "initiate host immune responses.

unc93b deficiency", "host immune responses.

unc93b deficiency has", "immune responses.

unc93b deficiency has been", "responses.

unc93b deficiency has been implicated", "deficiency has been implicated in", "has been implicated in the", "been implicated in the increased", "implicated in the increased susceptibility", "in the increased susceptibility to", "the increased susceptibility to herpes", "increased susceptibility to herpes simplex", "susceptibility to herpes simplex virus", "to herpes simplex virus type", "herpes simplex virus type 1", "virus type 1 hsv1", "1 hsv1 encephalitis", "hsv1 encephalitis hse", "hse a rare", "a rare complication during hsv", "rare complication during hsv 1", "complication during hsv 1 infection", "during hsv 1 infection of", "hsv 1 infection of the", "1 infection of the central", "infection of the central nervous", "of the central nervous system", "central nervous system cns", "cns casrouge a", "casrouge a et al. 2006", "a et al. 2006 .", "et al. 2006 . patients", "al. 2006 . patients derived", "2006 . patients derived unc96b1", ". patients derived unc96b1 deficient", "patients derived unc96b1 deficient fibroblasts", "derived unc96b1 deficient fibroblasts showed", "unc96b1 deficient fibroblasts showed an", "deficient fibroblasts showed an impaired", "fibroblasts showed an impaired production", "showed an impaired production of", "an impaired production of ifn", "impaired production of ifn beta", "production of ifn beta and", "beta and gamma following", "and gamma following stimulation", "gamma following stimulation with tlr3", "following stimulation with tlr3 agonist", "stimulation with tlr3 agonist poly", "with tlr3 agonist poly i:c", "poly i:c casrouge", "i:c casrouge a", "et al. 2006 . these", "al. 2006 . these cells", "2006 . these cells were", ". these cells were also", "these cells were also more", "cells were also more susceptible", "were also more susceptible to", "also more susceptible to hsv1", "more susceptible to hsv1 infection", "to hsv1 infection showing", "hsv1 infection showing rapid", "infection showing rapid viral", "showing rapid viral replication together", "rapid viral replication together with", "viral replication together with high", "replication together with high mortality", "together with high mortality rates.", "with high mortality rates. furthermore", "mortality rates. furthermore pluripotent", "rates. furthermore pluripotent stem", "furthermore pluripotent stem cells", "pluripotent stem cells ipsc", "cells ipsc derived", "ipsc derived from hse", "derived from hse patient dermal", "from hse patient dermal fibroblasts", "hse patient dermal fibroblasts were", "patient dermal fibroblasts were differentiated", "dermal fibroblasts were differentiated into", "fibroblasts were differentiated into populations", "were differentiated into populations of", "differentiated into populations of neural", "into populations of neural stem", "populations of neural stem cells", "neural stem cells nsc", "neurons astrocytes and oligodendrocytes", "astrocytes and oligodendrocytes lafaille", "and oligodendrocytes lafaille fg", "oligodendrocytes lafaille fg et", "lafaille fg et al. 2012", "fg et al. 2012 .", "et al. 2012 . the", "al. 2012 . the impaired", "2012 . the impaired induction", ". the impaired induction of", "the impaired induction of ifn", "impaired induction of ifn beta", "induction of ifn beta and", "of ifn beta and gamma", "ifn beta and gamma was", "beta and gamma was observed", "and gamma was observed in", "gamma was observed in all", "was observed in all tested", "observed in all tested cns", "in all tested cns cells", "all tested cns cells upon", "tested cns cells upon stimulation", "cns cells upon stimulation with", "cells upon stimulation with poly", "upon stimulation with poly i:c", "stimulation with poly i:c .", "with poly i:c . however", "i:c . however hsv1", ". however hsv1 infection", "however hsv1 infection selectively", "hsv1 infection selectively affected type", "infection selectively affected type i", "selectively affected type i and", "affected type i and iii", "type i and iii ifn", "i and iii ifn production", "and iii ifn production in", "iii ifn production in unc93b1", "ifn production in unc93b1 deficient", "production in unc93b1 deficient neurons", "in unc93b1 deficient neurons and", "unc93b1 deficient neurons and oligodendrocytes", "neurons and oligodendrocytes lafaille", "et al. 2012 . thus", "2012 . thus impaired", ". thus impaired tlr3", "thus impaired tlr3 mediated", "impaired tlr3 mediated unc93b dependent", "tlr3 mediated unc93b dependent type", "mediated unc93b dependent type i", "unc93b dependent type i and", "dependent type i and iii", "iii ifn production in respose", "ifn production in respose to", "production in respose to hsv1", "in respose to hsv1 infection", "respose to hsv1 infection in", "to hsv1 infection in cns", "infection in cns in", "in cns in neurons", "cns in neurons and", "in neurons and oligodendrocytes in", "neurons and oligodendrocytes in particular", "oligodendrocytes in particular may", "in particular may underline", "particular may underline the", "may underline the pathogenesis of", "underline the pathogenesis of hse", "the pathogenesis of hse in", "pathogenesis of hse in patients", "of hse in patients with", "hse in patients with unc93b1", "in patients with unc93b1 deficiency", "with unc93b1 deficiency casrouge", "unc93b1 deficiency casrouge a", "deficiency casrouge a et", "et al. 2006 lafaille", "al. 2006 lafaille fg", "2006 lafaille fg et", "fg et al. 2012 .

defective", "et al. 2012 .

defective unc93b1", "al. 2012 .

defective unc93b1 also", "2012 .

defective unc93b1 also impairs", ".

defective unc93b1 also impairs the", "unc93b1 also impairs the tlr7", "impairs the tlr7 tlr8", "the tlr7 tlr8 and", "tlr7 tlr8 and tlr9", "tlr8 and tlr9 signaling pathways.", "and tlr9 signaling pathways. peripheral", "tlr9 signaling pathways. peripheral blood", "pathways. peripheral blood mononuclear", "peripheral blood mononuclear cells", "cells pbmcs from", "pbmcs from unc93b deficient", "from unc93b deficient patients did", "unc93b deficient patients did not", "deficient patients did not respond", "patients did not respond to", "did not respond to the", "not respond to the stimulation", "respond to the stimulation of", "to the stimulation of tlr7", "stimulation of tlr7 tlr8", "tlr7 tlr8 or", "or tlr9 in terms", "tlr9 in terms of", "in terms of the production", "terms of the production of", "of the production of type", "the production of type i", "production of type i and", "of type i and iii", "type i and iii interferons", "and iii interferons and", "iii interferons and other", "interferons and other cytokines", "other cytokines tested casrouge", "cytokines tested casrouge a", "tested casrouge a et", "et al. 2006 . moreover", "2006 . moreover no", ". moreover no inducible", "moreover no inducible cd62l", "no inducible cd62l shedding on", "inducible cd62l shedding on granulocytes", "cd62l shedding on granulocytes was", "shedding on granulocytes was detected", "on granulocytes was detected after", "granulocytes was detected after stimulation", "was detected after stimulation of", "detected after stimulation of whole", "after stimulation of whole blood", "stimulation of whole blood cells", "of whole blood cells derived", "whole blood cells derived from", "blood cells derived from unc93b", "cells derived from unc93b deficients", "derived from unc93b deficients patients", "from unc93b deficients patients with", "unc93b deficients patients with r", "deficients patients with r 848", "with r 848 agonist", "r 848 agonist of", "848 agonist of tlr7", "agonist of tlr7 and tlr8", "and tlr8 von", "tlr8 von bernuth", "von bernuth h. et al.", "bernuth h. et al. 2008", "h. et al. 2008 .", "et al. 2008 . however", "2008 . however no", ". however no clinical", "however no clinical condition", "no clinical condition has been", "clinical condition has been so", "condition has been so far", "has been so far associated", "been so far associated with", "so far associated with impaired", "far associated with impaired tlr7", "with impaired tlr7 tlr8", "tlr7 tlr8 tlr9", "tlr8 tlr9 due to", "tlr9 due to unc93b1 deficiency", "due to unc93b1 deficiency so", "to unc93b1 deficiency so this", "unc93b1 deficiency so this defect", "deficiency so this defect is", "so this defect is not", "this defect is not annotated", "defect is not annotated here." ] }, { "record_id": "GLY_000594_1_442", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5602498", "r hsa", "hsa 5602498", "r hsa 5602498" ] }, { "record_id": "GLY_000594_1_442", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "myd88 deficiency", "deficiency tlr2/4", "myd88 deficiency tlr2/4", "myeloid differentiation", "differentiation primary", "primary response", "is an", "an adaptor", "adaptor protein", "protein that", "that mediates", "mediates intracellular", "intracellular signaling", "signaling pathways", "pathways evoked", "evoked by", "by all", "all toll", "toll like", "like receptors", "except for", "for tlr3", "tlr3 and", "and by", "by several", "several interleukin", "interleukin 1", "1 receptors", "il 1rs", "medzhitov r", "r et", "et al.", "al. 1998", "1998 .", ". upon", "upon ligand", "ligand binding", "tlrs hetero", "or homodimerize", "homodimerize and", "and recruit", "recruit myd88", "myd88 through", "through their", "their respective", "respective tir", "tir domains.", "domains. then", "myd88 oligomerizes", "oligomerizes via", "via its", "its death", "death domain", "and tir", "tir domain", "domain and", "and interacts", "interacts with", "with the", "the interleukin", "1 receptor", "receptor associated", "associated kinases", "to form", "form the", "the myddosome", "myddosome complex", "motshwene pg", "pg et", "al. 2009", "lin sc", "sc et", "al. 2010", "2010 .", ". the", "complex transmits", "transmits the", "the signal", "signal leading", "leading to", "to activation", "activation of", "of transcription", "transcription factors", "factors such", "such as", "as nuclear", "nuclear factor", "factor kappab", "and activator", "activator protein", "protein 1", "ap1 .

studies", ".

studies have", "have identified", "identified patients", "patients with", "with autosomal", "autosomal recessive", "form of", "of myd88", "deficiency caused", "caused by", "by homozygous", "homozygous or", "or compound", "compound heterozygous", "heterozygous mutations", "mutations in", "in myd88", "myd88 gene", "gene leading", "to abolished", "abolished protein", "protein production", "von bernuth", "bernuth et", "al. 2008", "2008 .", ". ar", "ar myd88", "deficiency is", "is a", "a type", "type of", "of a", "a primary", "primary immunodeficiency", "immunodeficiency characterized", "characterized by", "by greater", "greater susceptibility", "susceptibility to", "to pyogenic", "pyogenic bacteria", "as streptococcus", "streptococcus pneumoniae", "staphylococcus aureus", "aureus or", "or pseudomonas", "pseudomonas aeruginosa", "manifested in", "in infancy", "infancy and", "and early", "early childhood.", "childhood. patients", "with myd88", "deficiency show", "show delayed", "delayed or", "or weak", "weak signs", "signs of", "of inflammation", "picard c", "c et", "al. 2011", "2011 .

functional", ".

functional assessment", "assessment of", "deficiency revealed", "revealed that", "that cytokine", "cytokine responses", "responses were", "were impaired", "impaired in", "in patient", "patient derived", "derived blood", "blood cells", "cells upon", "upon stimulation", "stimulation with", "the agonists", "agonists of", "of tlr2", "tlr2 and", "and tlr4", "pam2csk4 and", "and lps", "lps respectively", "although some", "some were", "were produced", "produced in", "in response", "response to", "to lps.", ". nfkb", "nfkb luciferase", "luciferase reporter", "reporter gene", "gene assays", "assays using", "using human", "human embryonic", "embryonic kidney", "kidney 293", "cells showed", "showed that", "that myd88", "myd88 variants", "and r196c", "were compromised", "compromised in", "in their", "their ability", "ability to", "to enhance", "enhance nfkb", "nfkb activation", "yamamoto t", "t et", "al. 2014", "2014 .", "the molecular", "molecular basis", "basis for", "for the", "the observed", "observed functional", "functional effects", "reported for", "for selected", "selected mutations", "probably faulty", "faulty myddosome", "myddosome formation", "formation due", "due to", "to impaired", "impaired myd88", "myd88 oligomerization", "oligomerization and/or", "and/or interaction", "interaction with", "with irak4", "george j", "j et", "nagpal k", "k et", "2014 .

while", ".

while myd88", "deficiency might", "might be", "be expected", "expected to", "to perturb", "perturb myd88?irak4", "myd88?irak4 dependent", "dependent tlr7", "tlr7 and", "and tlr8", "tlr8 signaling", "signaling events", "events associated", "associated with", "the sensing", "sensing viral", "viral infections", "myd88 and", "and irak4", "irak4 deficiencies", "deficiencies have", "have so", "so far", "far not", "not been", "been reported", "reported to", "to be", "be susceptible", "susceptible to", "to viral", "viral infection.", "myeloid differentiation primary", "differentiation primary response", "response myd88", "myd88 is", "is an adaptor", "an adaptor protein", "adaptor protein that", "protein that mediates", "that mediates intracellular", "mediates intracellular signaling", "intracellular signaling pathways", "signaling pathways evoked", "pathways evoked by", "evoked by all", "by all toll", "all toll like", "toll like receptors", "receptors tlrs", "tlrs except", "except for tlr3", "for tlr3 and", "tlr3 and by", "and by several", "by several interleukin", "several interleukin 1", "interleukin 1 receptors", "receptors il", "medzhitov r et", "r et al.", "et al. 1998", "al. 1998 .", "1998 . upon", ". upon ligand", "upon ligand binding", "binding tlrs", "hetero or", "or homodimerize and", "homodimerize and recruit", "and recruit myd88", "recruit myd88 through", "myd88 through their", "through their respective", "their respective tir", "respective tir domains.", "tir domains. then", "then myd88", "myd88 oligomerizes via", "oligomerizes via its", "via its death", "its death domain", "domain dd", "dd and", "and tir domain", "tir domain and", "domain and interacts", "and interacts with", "interacts with the", "with the interleukin", "the interleukin 1", "interleukin 1 receptor", "1 receptor associated", "receptor associated kinases", "kinases iraks", "iraks to", "to form the", "form the myddosome", "the myddosome complex", "complex myd88:irak4:irak1/2", "motshwene pg et", "pg et al.", "et al. 2009", "2009 lin", "lin sc et", "sc et al.", "et al. 2010", "al. 2010 .", "2010 . the", ". the myddosome", "myddosome complex transmits", "complex transmits the", "transmits the signal", "the signal leading", "signal leading to", "leading to activation", "to activation of", "activation of transcription", "of transcription factors", "transcription factors such", "factors such as", "such as nuclear", "as nuclear factor", "nuclear factor kappab", "kappab nfkb", "nfkb and", "and activator protein", "activator protein 1", "1 ap1", "ap1 .

studies have", ".

studies have identified", "have identified patients", "identified patients with", "patients with autosomal", "with autosomal recessive", "recessive ar", "ar form", "form of myd88", "of myd88 deficiency", "myd88 deficiency caused", "deficiency caused by", "caused by homozygous", "by homozygous or", "homozygous or compound", "or compound heterozygous", "compound heterozygous mutations", "heterozygous mutations in", "mutations in myd88", "in myd88 gene", "myd88 gene leading", "gene leading to", "leading to abolished", "to abolished protein", "abolished protein production", "production von", "von bernuth et", "bernuth et al.", "et al. 2008", "al. 2008 .", "2008 . ar", ". ar myd88", "ar myd88 deficiency", "myd88 deficiency is", "deficiency is a", "is a type", "a type of", "type of a", "of a primary", "a primary immunodeficiency", "primary immunodeficiency characterized", "immunodeficiency characterized by", "characterized by greater", "by greater susceptibility", "greater susceptibility to", "susceptibility to pyogenic", "to pyogenic bacteria", "bacteria such", "such as streptococcus", "as streptococcus pneumoniae", "pneumoniae staphylococcus", "staphylococcus aureus or", "aureus or pseudomonas", "or pseudomonas aeruginosa", "aeruginosa manifested", "manifested in infancy", "in infancy and", "infancy and early", "and early childhood.", "early childhood. patients", "childhood. patients with", "patients with myd88", "with myd88 deficiency", "myd88 deficiency show", "deficiency show delayed", "show delayed or", "delayed or weak", "or weak signs", "weak signs of", "signs of inflammation", "inflammation picard", "picard c et", "c et al.", "2010 picard", "et al. 2011", "al. 2011 .

functional", "2011 .

functional assessment", ".

functional assessment of", "assessment of myd88", "myd88 deficiency revealed", "deficiency revealed that", "revealed that cytokine", "that cytokine responses", "cytokine responses were", "responses were impaired", "were impaired in", "impaired in patient", "in patient derived", "patient derived blood", "derived blood cells", "blood cells upon", "cells upon stimulation", "upon stimulation with", "stimulation with the", "with the agonists", "the agonists of", "agonists of tlr2", "of tlr2 and", "tlr2 and tlr4", "tlr4 pam2csk4", "pam2csk4 and lps", "and lps respectively", "although some were", "some were produced", "were produced in", "produced in response", "in response to", "response to lps.", "lps. von", "2008 . nfkb", ". nfkb luciferase", "nfkb luciferase reporter", "luciferase reporter gene", "reporter gene assays", "gene assays using", "assays using human", "using human embryonic", "human embryonic kidney", "embryonic kidney 293", "293 hek293t", "hek293t cells", "cells showed that", "showed that myd88", "that myd88 variants", "variants s34y", "s34y e52del", "e52del e53x", "e53x l93p", "l93p r98c", "r98c and", "r196c were", "were compromised in", "compromised in their", "in their ability", "their ability to", "ability to enhance", "to enhance nfkb", "enhance nfkb activation", "activation yamamoto", "yamamoto t et", "t et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the molecular", "the molecular basis", "molecular basis for", "basis for the", "for the observed", "the observed functional", "observed functional effects", "effects reported", "reported for selected", "for selected mutations", "probably faulty myddosome", "faulty myddosome formation", "myddosome formation due", "formation due to", "due to impaired", "to impaired myd88", "impaired myd88 oligomerization", "myd88 oligomerization and/or", "oligomerization and/or interaction", "and/or interaction with", "interaction with irak4", "irak4 george", "george j et", "j et al.", "2011 nagpal", "nagpal k et", "k et al.", "2011 yamamoto", "al. 2014 .

while", "2014 .

while myd88", ".

while myd88 deficiency", "myd88 deficiency might", "deficiency might be", "might be expected", "be expected to", "expected to perturb", "to perturb myd88?irak4", "perturb myd88?irak4 dependent", "myd88?irak4 dependent tlr7", "dependent tlr7 and", "tlr7 and tlr8", "and tlr8 signaling", "tlr8 signaling events", "signaling events associated", "events associated with", "associated with the", "with the sensing", "the sensing viral", "sensing viral infections", "infections patients", "with myd88 and", "myd88 and irak4", "and irak4 deficiencies", "irak4 deficiencies have", "deficiencies have so", "have so far", "so far not", "far not been", "not been reported", "been reported to", "reported to be", "to be susceptible", "be susceptible to", "susceptible to viral", "to viral infection.", "myeloid differentiation primary response", "primary response myd88", "myd88 is an", "is an adaptor protein", "an adaptor protein that", "adaptor protein that mediates", "protein that mediates intracellular", "that mediates intracellular signaling", "mediates intracellular signaling pathways", "intracellular signaling pathways evoked", "signaling pathways evoked by", "pathways evoked by all", "evoked by all toll", "by all toll like", "all toll like receptors", "like receptors tlrs", "tlrs except for", "except for tlr3 and", "for tlr3 and by", "tlr3 and by several", "and by several interleukin", "by several interleukin 1", "several interleukin 1 receptors", "1 receptors il", "receptors il 1rs", "1rs medzhitov", "medzhitov r et al.", "r et al. 1998", "et al. 1998 .", "al. 1998 . upon", "1998 . upon ligand", ". upon ligand binding", "ligand binding tlrs", "binding tlrs hetero", "tlrs hetero or", "hetero or homodimerize", "or homodimerize and recruit", "homodimerize and recruit myd88", "and recruit myd88 through", "recruit myd88 through their", "myd88 through their respective", "through their respective tir", "their respective tir domains.", "respective tir domains. then", "domains. then myd88", "then myd88 oligomerizes", "myd88 oligomerizes via its", "oligomerizes via its death", "via its death domain", "death domain dd", "dd and tir", "and tir domain and", "tir domain and interacts", "domain and interacts with", "and interacts with the", "interacts with the interleukin", "with the interleukin 1", "the interleukin 1 receptor", "interleukin 1 receptor associated", "1 receptor associated kinases", "associated kinases iraks", "iraks to form", "to form the myddosome", "form the myddosome complex", "myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene", "motshwene pg et al.", "pg et al. 2009", "al. 2009 lin", "2009 lin sc", "lin sc et al.", "sc et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the myddosome", ". the myddosome complex", "the myddosome complex transmits", "myddosome complex transmits the", "complex transmits the signal", "transmits the signal leading", "the signal leading to", "signal leading to activation", "leading to activation of", "to activation of transcription", "activation of transcription factors", "of transcription factors such", "transcription factors such as", "factors such as nuclear", "such as nuclear factor", "as nuclear factor kappab", "factor kappab nfkb", "nfkb and activator", "and activator protein 1", "protein 1 ap1", "1 ap1 .

studies", "ap1 .

studies have identified", ".

studies have identified patients", "have identified patients with", "identified patients with autosomal", "patients with autosomal recessive", "autosomal recessive ar", "ar form of", "form of myd88 deficiency", "of myd88 deficiency caused", "myd88 deficiency caused by", "deficiency caused by homozygous", "caused by homozygous or", "by homozygous or compound", "homozygous or compound heterozygous", "or compound heterozygous mutations", "compound heterozygous mutations in", "heterozygous mutations in myd88", "mutations in myd88 gene", "in myd88 gene leading", "myd88 gene leading to", "gene leading to abolished", "leading to abolished protein", "to abolished protein production", "protein production von", "production von bernuth", "von bernuth et al.", "bernuth et al. 2008", "et al. 2008 .", "al. 2008 . ar", "2008 . ar myd88", ". ar myd88 deficiency", "ar myd88 deficiency is", "myd88 deficiency is a", "deficiency is a type", "is a type of", "a type of a", "type of a primary", "of a primary immunodeficiency", "a primary immunodeficiency characterized", "primary immunodeficiency characterized by", "immunodeficiency characterized by greater", "characterized by greater susceptibility", "by greater susceptibility to", "greater susceptibility to pyogenic", "susceptibility to pyogenic bacteria", "pyogenic bacteria such", "bacteria such as", "such as streptococcus pneumoniae", "streptococcus pneumoniae staphylococcus", "pneumoniae staphylococcus aureus", "staphylococcus aureus or pseudomonas", "aureus or pseudomonas aeruginosa", "pseudomonas aeruginosa manifested", "aeruginosa manifested in", "manifested in infancy and", "in infancy and early", "infancy and early childhood.", "and early childhood. patients", "early childhood. patients with", "childhood. patients with myd88", "patients with myd88 deficiency", "with myd88 deficiency show", "myd88 deficiency show delayed", "deficiency show delayed or", "show delayed or weak", "delayed or weak signs", "or weak signs of", "weak signs of inflammation", "of inflammation picard", "inflammation picard c", "picard c et al.", "c et al. 2010", "al. 2010 picard", "2010 picard c", "c et al. 2011", "et al. 2011 .

functional", "al. 2011 .

functional assessment", "2011 .

functional assessment of", ".

functional assessment of myd88", "assessment of myd88 deficiency", "of myd88 deficiency revealed", "myd88 deficiency revealed that", "deficiency revealed that cytokine", "revealed that cytokine responses", "that cytokine responses were", "cytokine responses were impaired", "responses were impaired in", "were impaired in patient", "impaired in patient derived", "in patient derived blood", "patient derived blood cells", "derived blood cells upon", "blood cells upon stimulation", "cells upon stimulation with", "upon stimulation with the", "stimulation with the agonists", "with the agonists of", "the agonists of tlr2", "agonists of tlr2 and", "of tlr2 and tlr4", "and tlr4 pam2csk4", "tlr4 pam2csk4 and", "pam2csk4 and lps respectively", "respectively although", "although some were produced", "some were produced in", "were produced in response", "produced in response to", "in response to lps.", "to lps. von", "lps. von bernuth", "al. 2008 . nfkb", "2008 . nfkb luciferase", ". nfkb luciferase reporter", "nfkb luciferase reporter gene", "luciferase reporter gene assays", "reporter gene assays using", "gene assays using human", "assays using human embryonic", "using human embryonic kidney", "human embryonic kidney 293", "kidney 293 hek293t", "hek293t cells showed", "cells showed that myd88", "showed that myd88 variants", "myd88 variants s34y", "r98c and r196c", "and r196c were", "r196c were compromised", "were compromised in their", "compromised in their ability", "in their ability to", "their ability to enhance", "ability to enhance nfkb", "to enhance nfkb activation", "nfkb activation yamamoto", "activation yamamoto t", "yamamoto t et al.", "t et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the molecular", ". the molecular basis", "the molecular basis for", "molecular basis for the", "basis for the observed", "for the observed functional", "the observed functional effects", "functional effects reported", "effects reported for", "reported for selected mutations", "mutations probably", "probably faulty myddosome formation", "faulty myddosome formation due", "myddosome formation due to", "formation due to impaired", "due to impaired myd88", "to impaired myd88 oligomerization", "impaired myd88 oligomerization and/or", "myd88 oligomerization and/or interaction", "oligomerization and/or interaction with", "and/or interaction with irak4", "with irak4 george", "irak4 george j", "george j et al.", "j et al. 2011", "al. 2011 nagpal", "2011 nagpal k", "nagpal k et al.", "k et al. 2011", "al. 2011 yamamoto", "2011 yamamoto t", "et al. 2014 .

while", "al. 2014 .

while myd88", "2014 .

while myd88 deficiency", ".

while myd88 deficiency might", "myd88 deficiency might be", "deficiency might be expected", "might be expected to", "be expected to perturb", "expected to perturb myd88?irak4", "to perturb myd88?irak4 dependent", "perturb myd88?irak4 dependent tlr7", "myd88?irak4 dependent tlr7 and", "dependent tlr7 and tlr8", "tlr7 and tlr8 signaling", "and tlr8 signaling events", "tlr8 signaling events associated", "signaling events associated with", "events associated with the", "associated with the sensing", "with the sensing viral", "the sensing viral infections", "viral infections patients", "infections patients with", "patients with myd88 and", "with myd88 and irak4", "myd88 and irak4 deficiencies", "and irak4 deficiencies have", "irak4 deficiencies have so", "deficiencies have so far", "have so far not", "so far not been", "far not been reported", "not been reported to", "been reported to be", "reported to be susceptible", "to be susceptible to", "be susceptible to viral", "susceptible to viral infection.", "differentiation primary response myd88", "response myd88 is", "myd88 is an adaptor", "is an adaptor protein that", "an adaptor protein that mediates", "adaptor protein that mediates intracellular", "protein that mediates intracellular signaling", "that mediates intracellular signaling pathways", "mediates intracellular signaling pathways evoked", "intracellular signaling pathways evoked by", "signaling pathways evoked by all", "pathways evoked by all toll", "evoked by all toll like", "by all toll like receptors", "toll like receptors tlrs", "receptors tlrs except", "tlrs except for tlr3", "except for tlr3 and by", "for tlr3 and by several", "tlr3 and by several interleukin", "and by several interleukin 1", "by several interleukin 1 receptors", "interleukin 1 receptors il", "1 receptors il 1rs", "il 1rs medzhitov", "1rs medzhitov r", "medzhitov r et al. 1998", "r et al. 1998 .", "et al. 1998 . upon", "al. 1998 . upon ligand", "1998 . upon ligand binding", "upon ligand binding tlrs", "ligand binding tlrs hetero", "tlrs hetero or homodimerize", "hetero or homodimerize and", "or homodimerize and recruit myd88", "homodimerize and recruit myd88 through", "and recruit myd88 through their", "recruit myd88 through their respective", "myd88 through their respective tir", "through their respective tir domains.", "their respective tir domains. then", "tir domains. then myd88", "domains. then myd88 oligomerizes", "then myd88 oligomerizes via", "myd88 oligomerizes via its death", "oligomerizes via its death domain", "its death domain dd", "domain dd and", "dd and tir domain", "and tir domain and interacts", "tir domain and interacts with", "domain and interacts with the", "and interacts with the interleukin", "interacts with the interleukin 1", "with the interleukin 1 receptor", "the interleukin 1 receptor associated", "interleukin 1 receptor associated kinases", "receptor associated kinases iraks", "kinases iraks to", "iraks to form the", "to form the myddosome complex", "the myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene pg", "motshwene pg et al. 2009", "et al. 2009 lin", "al. 2009 lin sc", "2009 lin sc et", "lin sc et al. 2010", "sc et al. 2010 .", "et al. 2010 . the", "al. 2010 . the myddosome", "2010 . the myddosome complex", ". the myddosome complex transmits", "the myddosome complex transmits the", "myddosome complex transmits the signal", "complex transmits the signal leading", "transmits the signal leading to", "the signal leading to activation", "signal leading to activation of", "leading to activation of transcription", "to activation of transcription factors", "activation of transcription factors such", "of transcription factors such as", "transcription factors such as nuclear", "factors such as nuclear factor", "such as nuclear factor kappab", "nuclear factor kappab nfkb", "kappab nfkb and", "nfkb and activator protein", "activator protein 1 ap1", "protein 1 ap1 .

studies", "1 ap1 .

studies have", "ap1 .

studies have identified patients", ".

studies have identified patients with", "have identified patients with autosomal", "identified patients with autosomal recessive", "with autosomal recessive ar", "recessive ar form", "ar form of myd88", "form of myd88 deficiency caused", "of myd88 deficiency caused by", "myd88 deficiency caused by homozygous", "deficiency caused by homozygous or", "caused by homozygous or compound", "by homozygous or compound heterozygous", "homozygous or compound heterozygous mutations", "or compound heterozygous mutations in", "compound heterozygous mutations in myd88", "heterozygous mutations in myd88 gene", "mutations in myd88 gene leading", "in myd88 gene leading to", "myd88 gene leading to abolished", "gene leading to abolished protein", "leading to abolished protein production", "abolished protein production von", "protein production von bernuth", "production von bernuth et", "von bernuth et al. 2008", "bernuth et al. 2008 .", "et al. 2008 . ar", "al. 2008 . ar myd88", "2008 . ar myd88 deficiency", ". ar myd88 deficiency is", "ar myd88 deficiency is a", "myd88 deficiency is a type", "deficiency is a type of", "is a type of a", "a type of a primary", "type of a primary immunodeficiency", "of a primary immunodeficiency characterized", "a primary immunodeficiency characterized by", "primary immunodeficiency characterized by greater", "immunodeficiency characterized by greater susceptibility", "characterized by greater susceptibility to", "by greater susceptibility to pyogenic", "greater susceptibility to pyogenic bacteria", "to pyogenic bacteria such", "pyogenic bacteria such as", "bacteria such as streptococcus", "as streptococcus pneumoniae staphylococcus", "streptococcus pneumoniae staphylococcus aureus", "pneumoniae staphylococcus aureus or", "staphylococcus aureus or pseudomonas aeruginosa", "or pseudomonas aeruginosa manifested", "pseudomonas aeruginosa manifested in", "aeruginosa manifested in infancy", "manifested in infancy and early", "in infancy and early childhood.", "infancy and early childhood. patients", "and early childhood. patients with", "early childhood. patients with myd88", "childhood. patients with myd88 deficiency", "patients with myd88 deficiency show", "with myd88 deficiency show delayed", "myd88 deficiency show delayed or", "deficiency show delayed or weak", "show delayed or weak signs", "delayed or weak signs of", "or weak signs of inflammation", "signs of inflammation picard", "of inflammation picard c", "inflammation picard c et", "picard c et al. 2010", "et al. 2010 picard", "al. 2010 picard c", "2010 picard c et", "picard c et al. 2011", "c et al. 2011 .

functional", "et al. 2011 .

functional assessment", "al. 2011 .

functional assessment of", "2011 .

functional assessment of myd88", ".

functional assessment of myd88 deficiency", "assessment of myd88 deficiency revealed", "of myd88 deficiency revealed that", "myd88 deficiency revealed that cytokine", "deficiency revealed that cytokine responses", "revealed that cytokine responses were", "that cytokine responses were impaired", "cytokine responses were impaired in", "responses were impaired in patient", "were impaired in patient derived", "impaired in patient derived blood", "in patient derived blood cells", "patient derived blood cells upon", "derived blood cells upon stimulation", "blood cells upon stimulation with", "cells upon stimulation with the", "upon stimulation with the agonists", "stimulation with the agonists of", "with the agonists of tlr2", "the agonists of tlr2 and", "agonists of tlr2 and tlr4", "tlr2 and tlr4 pam2csk4", "and tlr4 pam2csk4 and", "tlr4 pam2csk4 and lps", "lps respectively although", "respectively although some", "although some were produced in", "some were produced in response", "were produced in response to", "produced in response to lps.", "response to lps. von", "to lps. von bernuth", "lps. von bernuth et", "et al. 2008 . nfkb", "al. 2008 . nfkb luciferase", "2008 . nfkb luciferase reporter", ". nfkb luciferase reporter gene", "nfkb luciferase reporter gene assays", "luciferase reporter gene assays using", "reporter gene assays using human", "gene assays using human embryonic", "assays using human embryonic kidney", "using human embryonic kidney 293", "embryonic kidney 293 hek293t", "293 hek293t cells", "hek293t cells showed that", "cells showed that myd88 variants", "that myd88 variants s34y", "variants s34y e52del", "s34y e52del e53x", "e52del e53x l93p", "e53x l93p r98c", "l93p r98c and", "and r196c were compromised", "r196c were compromised in", "were compromised in their ability", "compromised in their ability to", "in their ability to enhance", "their ability to enhance nfkb", "ability to enhance nfkb activation", "enhance nfkb activation yamamoto", "nfkb activation yamamoto t", "activation yamamoto t et", "yamamoto t et al. 2014", "t et al. 2014 .", "et al. 2014 . the", "al. 2014 . the molecular", "2014 . the molecular basis", ". the molecular basis for", "the molecular basis for the", "molecular basis for the observed", "basis for the observed functional", "for the observed functional effects", "observed functional effects reported", "functional effects reported for", "effects reported for selected", "selected mutations probably", "mutations probably faulty", "probably faulty myddosome formation due", "faulty myddosome formation due to", "myddosome formation due to impaired", "formation due to impaired myd88", "due to impaired myd88 oligomerization", "to impaired myd88 oligomerization and/or", "impaired myd88 oligomerization and/or interaction", "myd88 oligomerization and/or interaction with", "oligomerization and/or interaction with irak4", "interaction with irak4 george", "with irak4 george j", "irak4 george j et", "george j et al. 2011", "et al. 2011 nagpal", "al. 2011 nagpal k", "2011 nagpal k et", "nagpal k et al. 2011", "et al. 2011 yamamoto", "al. 2011 yamamoto t", "2011 yamamoto t et", "t et al. 2014 .

while", "et al. 2014 .

while myd88", "al. 2014 .

while myd88 deficiency", "2014 .

while myd88 deficiency might", ".

while myd88 deficiency might be", "myd88 deficiency might be expected", "deficiency might be expected to", "might be expected to perturb", "be expected to perturb myd88?irak4", "expected to perturb myd88?irak4 dependent", "to perturb myd88?irak4 dependent tlr7", "perturb myd88?irak4 dependent tlr7 and", "myd88?irak4 dependent tlr7 and tlr8", "dependent tlr7 and tlr8 signaling", "tlr7 and tlr8 signaling events", "and tlr8 signaling events associated", "tlr8 signaling events associated with", "signaling events associated with the", "events associated with the sensing", "associated with the sensing viral", "with the sensing viral infections", "sensing viral infections patients", "viral infections patients with", "infections patients with myd88", "patients with myd88 and irak4", "with myd88 and irak4 deficiencies", "myd88 and irak4 deficiencies have", "and irak4 deficiencies have so", "irak4 deficiencies have so far", "deficiencies have so far not", "have so far not been", "so far not been reported", "far not been reported to", "not been reported to be", "been reported to be susceptible", "reported to be susceptible to", "to be susceptible to viral", "be susceptible to viral infection." ] }, { "record_id": "GLY_000594_1_443", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5602566", "r hsa", "hsa 5602566", "r hsa 5602566" ] }, { "record_id": "GLY_000594_1_443", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ticam1 deficiency", "deficiency hse", "ticam1 deficiency hse", "inborn errors", "errors of", "of interferon", "interferon immunity", "immunity due", "due to", "to defects", "defects in", "in toll", "toll like", "like receptor", "receptor 3", "mediated signaling", "signaling underlie", "underlie pathogenesis", "pathogenesis of", "of herpes", "herpes simplex", "simplex virus", "virus type", "type 1", "in some", "some children", "netea mg", "mg et", "et al.", "al. 2012", "2012 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of", "low levels of immunoglobulins", "of immunoglobulins hypogammaglobulinemia", "immunoglobulins hypogammaglobulinemia .", "hypogammaglobulinemia . further phenotype", ". further phenotype assessment", "further phenotype assessment revealed", "phenotype assessment revealed that", "assessment revealed that patients", "revealed that patients peripheral", "that patients peripheral blood", "patients peripheral blood b", "peripheral blood b cells", "blood b cells and", "b cells and t", "cells and t cells", "and t cells had", "t cells had normal", "cells had normal counts", "had normal counts but", "normal counts but were", "counts but were almost", "but were almost exclusively", "were almost exclusively of", "almost exclusively of naive", "exclusively of naive phenotype.", "of naive phenotype. regulatory", "naive phenotype. regulatory t", "phenotype. regulatory t cells", "regulatory t cells and", "t cells and gamma", "cells and gamma delta", "and gamma delta t", "gamma delta t cells", "delta t cells were", "t cells were absent.", "four patients with early onset", "with early onset life", "early onset life threatening", "onset life threatening microbial", "life threatening microbial infections and", "threatening microbial infections and failure", "microbial infections and failure to", "infections and failure to thrive", "and failure to thrive were", "failure to thrive were found", "to thrive were found to", "thrive were found to carry", "were found to carry a", "found to carry a homozygous", "to carry a homozygous duplication", "carry a homozygous duplication c.1292dupg", "a homozygous duplication c.1292dupg in", "homozygous duplication c.1292dupg in exon", "duplication c.1292dupg in exon 13", "c.1292dupg in exon 13 of", "in exon 13 of ikbkb", "exon 13 of ikbkb gene", "13 of ikbkb gene that", "of ikbkb gene that results", "ikbkb gene that results in", "gene that results in a", "that results in a lack", "results in a lack of", "in a lack of expression", "a lack of expression of", "lack of expression of ikbkb", "expression of ikbkb pannicke", "of ikbkb pannicke u", "ikbkb pannicke u et", "pannicke u et al. 2013", "u et al. 2013 .", "et al. 2013 . ikbkb", "al. 2013 . ikbkb deficiency", "2013 . ikbkb deficiency is", ". ikbkb deficiency is associated", "ikbkb deficiency is associated with", "deficiency is associated with severe", "is associated with severe combined", "associated with severe combined immunodeficiency", "severe combined immunodeficiency scid", "scid a health", "a health condition characterized by", "health condition characterized by low", "condition characterized by low levels", "characterized by low levels of", "by low levels of immunoglobulins", "levels of immunoglobulins hypogammaglobulinemia", "of immunoglobulins hypogammaglobulinemia .", "immunoglobulins hypogammaglobulinemia . further", "hypogammaglobulinemia . further phenotype assessment", ". further phenotype assessment revealed", "further phenotype assessment revealed that", "phenotype assessment revealed that patients", "assessment revealed that patients peripheral", "revealed that patients peripheral blood", "that patients peripheral blood b", "patients peripheral blood b cells", "peripheral blood b cells and", "blood b cells and t", "b cells and t cells", "cells and t cells had", "and t cells had normal", "t cells had normal counts", "cells had normal counts but", "had normal counts but were", "normal counts but were almost", "counts but were almost exclusively", "but were almost exclusively of", "were almost exclusively of naive", "almost exclusively of naive phenotype.", "exclusively of naive phenotype. regulatory", "of naive phenotype. regulatory t", "naive phenotype. regulatory t cells", "phenotype. regulatory t cells and", "regulatory t cells and gamma", "t cells and gamma delta", "cells and gamma delta t", "and gamma delta t cells", "gamma delta t cells were", "delta t cells were absent." ] }, { "record_id": "GLY_000594_1_446", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5603027", "r hsa", "hsa 5603027", "r hsa 5603027" ] }, { "record_id": "GLY_000594_1_446", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ikbkg deficiency", "deficiency causes", "causes anhidrotic", "anhidrotic ectodermal", "ectodermal dysplasia", "dysplasia with", "with immunodeficiency", "eda id", "via tlr", "ikbkg deficiency causes", "deficiency causes anhidrotic", "causes anhidrotic ectodermal", "anhidrotic ectodermal dysplasia", "ectodermal dysplasia with", "dysplasia with immunodeficiency", "immunodeficiency eda", "ikbkg deficiency causes anhidrotic", "deficiency causes anhidrotic ectodermal", "causes anhidrotic ectodermal dysplasia", "anhidrotic ectodermal dysplasia with", "ectodermal dysplasia with immunodeficiency", "with immunodeficiency eda", "immunodeficiency eda id", "id via", "ikbkg deficiency causes anhidrotic ectodermal", "deficiency causes anhidrotic ectodermal dysplasia", "causes anhidrotic ectodermal dysplasia with", "anhidrotic ectodermal dysplasia with immunodeficiency", "dysplasia with immunodeficiency eda", "with immunodeficiency eda id", "eda id via", "id via tlr", "many signaling", "signaling pathways", "pathways rely", "rely on", "on the", "the activation", "activation of", "of nuclear", "nuclear factor", "factor kappa", "kappa b", "which is", "is critical", "critical for", "for the", "the induction", "induction of", "of the", "the appropriate", "appropriate cellular", "cellular function", "function in", "in response", "response to", "to various", "various stimuli", "stimuli such", "such as", "as inflammatory", "inflammatory cytokines", "microbial products", "products or", "or various", "various types", "types of", "of stress", "lawrence t", "t 2009", "hoesel b", "b and", "and schmid", "schmid ja", "ja 2013", "2013 .", ". the", "the nfkb", "nfkb family", "family of", "of transcription", "transcription factors", "factors is", "is kept", "kept inactive", "inactive in", "in the", "the cytoplasm", "cytoplasm by", "by inhibitor", "inhibitor of", "of kappa", "family members", "oeckinghaus a", "a and", "and ghosh", "ghosh s", "s 2009", "2009 .", ". canonical", "canonical nfkb", "nfkb activation", "activation depends", "depends on", "the phosphorylation", "phosphorylation of", "of ikb", "ikb by", "by the", "the i", "i kappa", "b kinase", "which contains", "contains two", "two catalytic", "catalytic subunits", "subunits named", "named ikk", "ikk alpha", "ikk beta", "beta and", "and a", "a regulatory", "regulatory subunit", "subunit named", "named nfkb", "nfkb essential", "essential modulator", "nemo or", "or ikbkg", "rothwarf dm", "dm et", "et al.", "al. 1998", "1998 .", ". phosphorylation", "ikb leads", "leads to", "to k48", "k48 linked", "linked ubiquitination", "ubiquitination and", "and proteasomal", "proteasomal degradation", "degradation of", "allowing translocation", "translocation of", "of nfkb", "nfkb factor", "factor to", "to the", "the nucleus", "where it", "it can", "can activate", "activate transcription", "transcription of", "of a", "a variety", "variety of", "of genes", "genes participating", "participating in", "the immune", "immune and", "and inflammatory", "inflammatory response", "cell adhesion", "growth control", "and protection", "protection against", "against apoptosis", "collins t", "t et", "al. 1995", "kaltschmidt b", "b et", "al. 2000", "2009 .

ikbkg", ".

ikbkg is", "is encoded", "encoded by", "by an", "an x", "x linked", "linked gene.", "gene. null", "null alleles", "alleles of", "the gene", "gene are", "are lethal", "lethal in", "in hemizygous", "hemizygous males", "whereas hypomorphic", "hypomorphic alleles", "alleles typically", "typically result", "result in", "the impaired", "impaired nfkb", "nfkb signaling", "signaling in", "in patients", "patients with", "with a", "a broad", "broad spectrum", "spectrum of", "of clinical", "clinical phenotypes", "phenotypes in", "in terms", "terms of", "of both", "both developmental", "developmental defects", "defects and", "and immunodeficiency", "d\u00f6ffinger r", "r et", "al. 2001", "hanson ep", "ep et", "al. 2008", "2008 .", ". several", "several categories", "categories of", "of mutations", "mutations affecting", "affecting ikbkg", "ikbkg have", "have been", "been reported", "reported in", "in humans", "vinolo e", "e et", "al. 2006", "fusko f", "f et", "the first", "first category", "category of", "of these", "these mutations", "mutations consists", "consists of", "of hypomorphic", "hypomorphic mutations", "mutations typically", "typically involving", "involving the", "the zinc", "zinc finger", "finger domain", "domain and", "and nearby", "nearby c", "c terminal", "terminal regions", "regions and", "and causing", "causing hypohidrotic", "hypohidrotic ectodermal", "with immune", "immune deficiency", "hed id", "in males", "jain a", "a et", "shifera as", "as 2010", "2010 .", "the second", "second category", "category consists", "of amorphic", "amorphic mutations", "mutations causing", "causing incontinentia", "incontinentia pigmenti", "in females", "females and", "prenatal death", "death in", "aradhya s", "s et", "fusco f", "al. 2004", "2004 .", "the third", "third category", "category is", "is composed", "composed of", "mutations involving", "the stop", "stop codon", "codon causing", "causing anhidrotic", "osteopetrosis and", "and lymphedema", "ol eda", "2001 .", ". also", "also some", "some patients", "a defective", "defective ikbkg", "ikbkg gene", "gene can", "can develop", "develop immunodeficiency", "immunodeficiency without", "without ectodermal", "orange js", "js et", ". this", "this module", "module describes", "describes several", "several eda", "id associated", "associated hypomorphic", "hypomorphic ikbkg", "ikbkg mutations", "mutations that", "that have", "reported to", "to affect", "affect inflammatory", "inflammatory responses", "responses initiated", "initiated by", "by toll", "toll like", "like receptors", "tlr .", "many signaling pathways", "signaling pathways rely", "pathways rely on", "rely on the", "on the activation", "the activation of", "activation of nuclear", "of nuclear factor", "nuclear factor kappa", "factor kappa b", "b nfkb", "which is critical", "is critical for", "critical for the", "for the induction", "the induction of", "induction of the", "of the appropriate", "the appropriate cellular", "appropriate cellular function", "cellular function in", "function in response", "in response to", "response to various", "to various stimuli", "various stimuli such", "stimuli such as", "such as inflammatory", "as inflammatory cytokines", "cytokines microbial", "microbial products or", "products or various", "or various types", "various types of", "types of stress", "stress lawrence", "lawrence t 2009", "2009 hoesel", "hoesel b and", "b and schmid", "and schmid ja", "schmid ja 2013", "ja 2013 .", "2013 . the", ". the nfkb", "the nfkb family", "nfkb family of", "family of transcription", "of transcription factors", "transcription factors is", "factors is kept", "is kept inactive", "kept inactive in", "inactive in the", "in the cytoplasm", "the cytoplasm by", "cytoplasm by inhibitor", "by inhibitor of", "inhibitor of kappa", "of kappa b", "b ikb", "ikb family", "members oeckinghaus", "oeckinghaus a and", "a and ghosh", "and ghosh s", "ghosh s 2009", "s 2009 .", "2009 . canonical", ". canonical nfkb", "canonical nfkb activation", "nfkb activation depends", "activation depends on", "depends on the", "on the phosphorylation", "the phosphorylation of", "phosphorylation of ikb", "of ikb by", "ikb by the", "by the i", "the i kappa", "i kappa b", "kappa b kinase", "kinase ikk", "ikk complex", "complex which", "which contains two", "contains two catalytic", "two catalytic subunits", "catalytic subunits named", "subunits named ikk", "named ikk alpha", "alpha ikk", "ikk beta and", "beta and a", "and a regulatory", "a regulatory subunit", "regulatory subunit named", "subunit named nfkb", "named nfkb essential", "nfkb essential modulator", "modulator nemo", "nemo or ikbkg", "rothwarf dm et", "dm et al.", "et al. 1998", "al. 1998 .", "1998 . phosphorylation", ". phosphorylation of", "of ikb leads", "ikb leads to", "leads to k48", "to k48 linked", "k48 linked ubiquitination", "linked ubiquitination and", "ubiquitination and proteasomal", "and proteasomal degradation", "proteasomal degradation of", "degradation of ikb", "ikb allowing", "allowing translocation of", "translocation of nfkb", "of nfkb factor", "nfkb factor to", "factor to the", "to the nucleus", "nucleus where", "where it can", "it can activate", "can activate transcription", "activate transcription of", "transcription of a", "of a variety", "a variety of", "variety of genes", "of genes participating", "genes participating in", "participating in the", "in the immune", "the immune and", "immune and inflammatory", "and inflammatory response", "response cell", "adhesion growth", "control and", "and protection against", "protection against apoptosis", "apoptosis collins", "collins t et", "t et al.", "et al. 1995", "1995 kaltschmidt", "kaltschmidt b et", "b et al.", "et al. 2000", "2000 lawrence", "t 2009 .

ikbkg", "2009 .

ikbkg is", ".

ikbkg is encoded", "is encoded by", "encoded by an", "by an x", "an x linked", "x linked gene.", "linked gene. null", "gene. null alleles", "null alleles of", "alleles of the", "of the gene", "the gene are", "gene are lethal", "are lethal in", "lethal in hemizygous", "in hemizygous males", "males whereas", "whereas hypomorphic alleles", "hypomorphic alleles typically", "alleles typically result", "typically result in", "result in the", "in the impaired", "the impaired nfkb", "impaired nfkb signaling", "nfkb signaling in", "signaling in patients", "in patients with", "patients with a", "with a broad", "a broad spectrum", "broad spectrum of", "spectrum of clinical", "of clinical phenotypes", "clinical phenotypes in", "phenotypes in terms", "in terms of", "terms of both", "of both developmental", "both developmental defects", "developmental defects and", "defects and immunodeficiency", "immunodeficiency d\u00f6ffinger", "d\u00f6ffinger r et", "r et al.", "et al. 2001", "2001 hanson", "hanson ep et", "ep et al.", "et al. 2008", "al. 2008 .", "2008 . several", ". several categories", "several categories of", "categories of mutations", "of mutations affecting", "mutations affecting ikbkg", "affecting ikbkg have", "ikbkg have been", "have been reported", "been reported in", "reported in humans", "humans d\u00f6ffinger", "2001 vinolo", "vinolo e et", "e et al.", "et al. 2006", "2006 fusko", "fusko f et", "f et al.", "2008 . the", ". the first", "the first category", "first category of", "category of these", "of these mutations", "these mutations consists", "mutations consists of", "consists of hypomorphic", "of hypomorphic mutations", "hypomorphic mutations typically", "mutations typically involving", "typically involving the", "involving the zinc", "the zinc finger", "zinc finger domain", "finger domain and", "domain and nearby", "and nearby c", "nearby c terminal", "c terminal regions", "terminal regions and", "regions and causing", "and causing hypohidrotic", "causing hypohidrotic ectodermal", "hypohidrotic ectodermal dysplasia", "dysplasia with immune", "with immune deficiency", "deficiency hed", "id in", "males jain", "jain a et", "a et al.", "2001 shifera", "shifera as 2010", "as 2010 .", "2010 . the", ". the second", "the second category", "second category consists", "category consists of", "consists of amorphic", "of amorphic mutations", "amorphic mutations causing", "mutations causing incontinentia", "causing incontinentia pigmenti", "pigmenti ip", "ip in", "in females and", "and generally", "generally prenatal", "prenatal death in", "death in males", "males aradhya", "aradhya s et", "s et al.", "2001 fusco", "fusco f et", "et al. 2004", "al. 2004 .", "2004 . the", ". the third", "the third category", "third category is", "category is composed", "is composed of", "composed of hypomorphic", "hypomorphic mutations involving", "mutations involving the", "involving the stop", "the stop codon", "stop codon causing", "codon causing anhidrotic", "causing anhidrotic ectodermal", "osteopetrosis and lymphedema", "lymphedema ol", "ol eda id", "males d\u00f6ffinger", "al. 2001 .", "2001 . also", ". also some", "also some patients", "some patients with", "with a defective", "a defective ikbkg", "defective ikbkg gene", "ikbkg gene can", "gene can develop", "can develop immunodeficiency", "develop immunodeficiency without", "immunodeficiency without ectodermal", "without ectodermal dysplasia", "dysplasia orange", "orange js et", "js et al.", "2004 . this", ". this module", "this module describes", "module describes several", "describes several eda", "several eda id", "eda id associated", "id associated hypomorphic", "associated hypomorphic ikbkg", "hypomorphic ikbkg mutations", "ikbkg mutations that", "mutations that have", "that have been", "been reported to", "reported to affect", "to affect inflammatory", "affect inflammatory responses", "inflammatory responses initiated", "responses initiated by", "initiated by toll", "by toll like", "toll like receptors", "receptors tlr", "many signaling pathways rely", "signaling pathways rely on", "pathways rely on the", "rely on the activation", "on the activation of", "the activation of nuclear", "activation of nuclear factor", "of nuclear factor kappa", "nuclear factor kappa b", "kappa b nfkb", "nfkb which", "which is critical for", "is critical for the", "critical for the induction", "for the induction of", "the induction of the", "induction of the appropriate", "of the appropriate cellular", "the appropriate cellular function", "appropriate cellular function in", "cellular function in response", "function in response to", "in response to various", "response to various stimuli", "to various stimuli such", "various stimuli such as", "stimuli such as inflammatory", "such as inflammatory cytokines", "inflammatory cytokines microbial", "cytokines microbial products", "microbial products or various", "products or various types", "or various types of", "various types of stress", "of stress lawrence", "stress lawrence t", "t 2009 hoesel", "2009 hoesel b", "hoesel b and schmid", "b and schmid ja", "and schmid ja 2013", "schmid ja 2013 .", "ja 2013 . the", "2013 . the nfkb", ". the nfkb family", "the nfkb family of", "nfkb family of transcription", "family of transcription factors", "of transcription factors is", "transcription factors is kept", "factors is kept inactive", "is kept inactive in", "kept inactive in the", "inactive in the cytoplasm", "in the cytoplasm by", "the cytoplasm by inhibitor", "cytoplasm by inhibitor of", "by inhibitor of kappa", "inhibitor of kappa b", "kappa b ikb", "ikb family members", "family members oeckinghaus", "members oeckinghaus a", "oeckinghaus a and ghosh", "a and ghosh s", "and ghosh s 2009", "ghosh s 2009 .", "s 2009 . canonical", "2009 . canonical nfkb", ". canonical nfkb activation", "canonical nfkb activation depends", "nfkb activation depends on", "activation depends on the", "depends on the phosphorylation", "on the phosphorylation of", "the phosphorylation of ikb", "phosphorylation of ikb by", "of ikb by the", "ikb by the i", "by the i kappa", "the i kappa b", "i kappa b kinase", "b kinase ikk", "complex which contains", "which contains two catalytic", "contains two catalytic subunits", "two catalytic subunits named", "catalytic subunits named ikk", "subunits named ikk alpha", "ikk alpha ikk", "alpha ikk beta", "ikk beta and a", "beta and a regulatory", "and a regulatory subunit", "a regulatory subunit named", "regulatory subunit named nfkb", "subunit named nfkb essential", "named nfkb essential modulator", "essential modulator nemo", "modulator nemo or", "ikbkg rothwarf", "rothwarf dm et al.", "dm et al. 1998", "et al. 1998 .", "al. 1998 . phosphorylation", "1998 . phosphorylation of", ". phosphorylation of ikb", "phosphorylation of ikb leads", "of ikb leads to", "ikb leads to k48", "leads to k48 linked", "to k48 linked ubiquitination", "k48 linked ubiquitination and", "linked ubiquitination and proteasomal", "ubiquitination and proteasomal degradation", "and proteasomal degradation of", "proteasomal degradation of ikb", "of ikb allowing", "ikb allowing translocation", "allowing translocation of nfkb", "translocation of nfkb factor", "of nfkb factor to", "nfkb factor to the", "factor to the nucleus", "the nucleus where", "nucleus where it", "where it can activate", "it can activate transcription", "can activate transcription of", "activate transcription of a", "transcription of a variety", "of a variety of", "a variety of genes", "variety of genes participating", "of genes participating in", "genes participating in the", "participating in the immune", "in the immune and", "the immune and inflammatory", "immune and inflammatory response", "inflammatory response cell", "response cell adhesion", "cell adhesion growth", "adhesion growth control", "growth control and", "control and protection", "and protection against apoptosis", "against apoptosis collins", "apoptosis collins t", "collins t et al.", "t et al. 1995", "al. 1995 kaltschmidt", "1995 kaltschmidt b", "kaltschmidt b et al.", "b et al. 2000", "al. 2000 lawrence", "2000 lawrence t", "lawrence t 2009 .

ikbkg", "t 2009 .

ikbkg is", "2009 .

ikbkg is encoded", ".

ikbkg is encoded by", "is encoded by an", "encoded by an x", "by an x linked", "an x linked gene.", "x linked gene. null", "linked gene. null alleles", "gene. null alleles of", "null alleles of the", "alleles of the gene", "of the gene are", "the gene are lethal", "gene are lethal in", "are lethal in hemizygous", "lethal in hemizygous males", "hemizygous males whereas", "males whereas hypomorphic", "whereas hypomorphic alleles typically", "hypomorphic alleles typically result", "alleles typically result in", "typically result in the", "result in the impaired", "in the impaired nfkb", "the impaired nfkb signaling", "impaired nfkb signaling in", "nfkb signaling in patients", "signaling in patients with", "in patients with a", "patients with a broad", "with a broad spectrum", "a broad spectrum of", "broad spectrum of clinical", "spectrum of clinical phenotypes", "of clinical phenotypes in", "clinical phenotypes in terms", "phenotypes in terms of", "in terms of both", "terms of both developmental", "of both developmental defects", "both developmental defects and", "developmental defects and immunodeficiency", "and immunodeficiency d\u00f6ffinger", "immunodeficiency d\u00f6ffinger r", "d\u00f6ffinger r et al.", "r et al. 2001", "al. 2001 hanson", "2001 hanson ep", "hanson ep et al.", "ep et al. 2008", "et al. 2008 .", "al. 2008 . several", "2008 . several categories", ". several categories of", "several categories of mutations", "categories of mutations affecting", "of mutations affecting ikbkg", "mutations affecting ikbkg have", "affecting ikbkg have been", "ikbkg have been reported", "have been reported in", "been reported in humans", "in humans d\u00f6ffinger", "humans d\u00f6ffinger r", "al. 2001 vinolo", "2001 vinolo e", "vinolo e et al.", "e et al. 2006", "al. 2006 fusko", "2006 fusko f", "fusko f et al.", "f et al. 2008", "al. 2008 . the", "2008 . the first", ". the first category", "the first category of", "first category of these", "category of these mutations", "of these mutations consists", "these mutations consists of", "mutations consists of hypomorphic", "consists of hypomorphic mutations", "of hypomorphic mutations typically", "hypomorphic mutations typically involving", "mutations typically involving the", "typically involving the zinc", "involving the zinc finger", "the zinc finger domain", "zinc finger domain and", "finger domain and nearby", "domain and nearby c", "and nearby c terminal", "nearby c terminal regions", "c terminal regions and", "terminal regions and causing", "regions and causing hypohidrotic", "and causing hypohidrotic ectodermal", "causing hypohidrotic ectodermal dysplasia", "hypohidrotic ectodermal dysplasia with", "ectodermal dysplasia with immune", "dysplasia with immune deficiency", "immune deficiency hed", "deficiency hed id", "hed id in", "id in males", "in males jain", "males jain a", "jain a et al.", "a et al. 2001", "al. 2001 shifera", "2001 shifera as", "shifera as 2010 .", "as 2010 . the", "2010 . the second", ". the second category", "the second category consists", "second category consists of", "category consists of amorphic", "consists of amorphic mutations", "of amorphic mutations causing", "amorphic mutations causing incontinentia", "mutations causing incontinentia pigmenti", "incontinentia pigmenti ip", "ip in females", "females and generally", "generally prenatal death", "prenatal death in males", "in males aradhya", "males aradhya s", "aradhya s et al.", "s et al. 2001", "al. 2001 fusco", "2001 fusco f", "fusco f et al.", "f et al. 2004", "et al. 2004 .", "al. 2004 . the", "2004 . the third", ". the third category", "the third category is", "third category is composed", "category is composed of", "is composed of hypomorphic", "composed of hypomorphic mutations", "of hypomorphic mutations involving", "hypomorphic mutations involving the", "mutations involving the stop", "involving the stop codon", "the stop codon causing", "stop codon causing anhidrotic", "codon causing anhidrotic ectodermal", "causing anhidrotic ectodermal dysplasia", "id osteopetrosis", "and lymphedema ol", "lymphedema ol eda", "eda id in", "in males d\u00f6ffinger", "males d\u00f6ffinger r", "et al. 2001 .", "al. 2001 . also", "2001 . also some", ". also some patients", "also some patients with", "some patients with a", "patients with a defective", "with a defective ikbkg", "a defective ikbkg gene", "defective ikbkg gene can", "ikbkg gene can develop", "gene can develop immunodeficiency", "can develop immunodeficiency without", "develop immunodeficiency without ectodermal", "immunodeficiency without ectodermal dysplasia", "ectodermal dysplasia orange", "dysplasia orange js", "orange js et al.", "js et al. 2004", "al. 2004 . this", "2004 . this module", ". this module describes", "this module describes several", "module describes several eda", "describes several eda id", "several eda id associated", "eda id associated hypomorphic", "id associated hypomorphic ikbkg", "associated hypomorphic ikbkg mutations", "hypomorphic ikbkg mutations that", "ikbkg mutations that have", "mutations that have been", "that have been reported", "have been reported to", "been reported to affect", "reported to affect inflammatory", "to affect inflammatory responses", "affect inflammatory responses initiated", "inflammatory responses initiated by", "responses initiated by toll", "initiated by toll like", "by toll like receptors", "like receptors tlr", "receptors tlr .", "many signaling pathways rely on", "signaling pathways rely on the", "pathways rely on the activation", "rely on the activation of", "on the activation of nuclear", "the activation of nuclear factor", "activation of nuclear factor kappa", "of nuclear factor kappa b", "factor kappa b nfkb", "nfkb which is", "which is critical for the", "is critical for the induction", "critical for the induction of", "for the induction of the", "the induction of the appropriate", "induction of the appropriate cellular", "of the appropriate cellular function", "the appropriate cellular function in", "appropriate cellular function in response", "cellular function in response to", "function in response to various", "in response to various stimuli", "response to various stimuli such", "to various stimuli such as", "various stimuli such as inflammatory", "stimuli such as inflammatory cytokines", "as inflammatory cytokines microbial", "inflammatory cytokines microbial products", "cytokines microbial products or", "microbial products or various types", "products or various types of", "or various types of stress", "types of stress lawrence", "of stress lawrence t", "stress lawrence t 2009", "lawrence t 2009 hoesel", "t 2009 hoesel b", "2009 hoesel b and", "hoesel b and schmid ja", "b and schmid ja 2013", "and schmid ja 2013 .", "schmid ja 2013 . the", "ja 2013 . the nfkb", "2013 . the nfkb family", ". the nfkb family of", "the nfkb family of transcription", "nfkb family of transcription factors", "family of transcription factors is", "of transcription factors is kept", "transcription factors is kept inactive", "factors is kept inactive in", "is kept inactive in the", "kept inactive in the cytoplasm", "inactive in the cytoplasm by", "in the cytoplasm by inhibitor", "the cytoplasm by inhibitor of", "cytoplasm by inhibitor of kappa", "by inhibitor of kappa b", "of kappa b ikb", "b ikb family", "family members oeckinghaus a", "members oeckinghaus a and", "oeckinghaus a and ghosh s", "a and ghosh s 2009", "and ghosh s 2009 .", "ghosh s 2009 . canonical", "s 2009 . canonical nfkb", "2009 . canonical nfkb activation", ". canonical nfkb activation depends", "canonical nfkb activation depends on", "nfkb activation depends on the", "activation depends on the phosphorylation", "depends on the phosphorylation of", "on the phosphorylation of ikb", "the phosphorylation of ikb by", "phosphorylation of ikb by the", "of ikb by the i", "ikb by the i kappa", "by the i kappa b", "the i kappa b kinase", "kappa b kinase ikk", "kinase ikk complex", "ikk complex which", "complex which contains two", "which contains two catalytic subunits", "contains two catalytic subunits named", "two catalytic subunits named ikk", "catalytic subunits named ikk alpha", "named ikk alpha ikk", "ikk alpha ikk beta", "alpha ikk beta and", "ikk beta and a regulatory", "beta and a regulatory subunit", "and a regulatory subunit named", "a regulatory subunit named nfkb", "regulatory subunit named nfkb essential", "subunit named nfkb essential modulator", "nfkb essential modulator nemo", "essential modulator nemo or", "modulator nemo or ikbkg", "or ikbkg rothwarf", "ikbkg rothwarf dm", "rothwarf dm et al. 1998", "dm et al. 1998 .", "et al. 1998 . phosphorylation", "al. 1998 . phosphorylation of", "1998 . phosphorylation of ikb", ". phosphorylation of ikb leads", "phosphorylation of ikb leads to", "of ikb leads to k48", "ikb leads to k48 linked", "leads to k48 linked ubiquitination", "to k48 linked ubiquitination and", "k48 linked ubiquitination and proteasomal", "linked ubiquitination and proteasomal degradation", "ubiquitination and proteasomal degradation of", "and proteasomal degradation of ikb", "degradation of ikb allowing", "of ikb allowing translocation", "ikb allowing translocation of", "allowing translocation of nfkb factor", "translocation of nfkb factor to", "of nfkb factor to the", "nfkb factor to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it can", "where it can activate transcription", "it can activate transcription of", "can activate transcription of a", "activate transcription of a variety", "transcription of a variety of", "of a variety of genes", "a variety of genes participating", "variety of genes participating in", "of genes participating in the", "genes participating in the immune", "participating in the immune and", "in the immune and inflammatory", "the immune and inflammatory response", "and inflammatory response cell", "inflammatory response cell adhesion", "cell adhesion growth control", "growth control and protection", "control and protection against", "protection against apoptosis collins", "against apoptosis collins t", "apoptosis collins t et", "collins t et al. 1995", "et al. 1995 kaltschmidt", "al. 1995 kaltschmidt b", "1995 kaltschmidt b et", "kaltschmidt b et al. 2000", "et al. 2000 lawrence", "al. 2000 lawrence t", "2000 lawrence t 2009", "lawrence t 2009 .

ikbkg is", "t 2009 .

ikbkg is encoded", "2009 .

ikbkg is encoded by", ".

ikbkg is encoded by an", "is encoded by an x", "encoded by an x linked", "by an x linked gene.", "an x linked gene. null", "x linked gene. null alleles", "linked gene. null alleles of", "gene. null alleles of the", "null alleles of the gene", "alleles of the gene are", "of the gene are lethal", "the gene are lethal in", "gene are lethal in hemizygous", "are lethal in hemizygous males", "in hemizygous males whereas", "hemizygous males whereas hypomorphic", "males whereas hypomorphic alleles", "whereas hypomorphic alleles typically result", "hypomorphic alleles typically result in", "alleles typically result in the", "typically result in the impaired", "result in the impaired nfkb", "in the impaired nfkb signaling", "the impaired nfkb signaling in", "impaired nfkb signaling in patients", "nfkb signaling in patients with", "signaling in patients with a", "in patients with a broad", "patients with a broad spectrum", "with a broad spectrum of", "a broad spectrum of clinical", "broad spectrum of clinical phenotypes", "spectrum of clinical phenotypes in", "of clinical phenotypes in terms", "clinical phenotypes in terms of", "phenotypes in terms of both", "in terms of both developmental", "terms of both developmental defects", "of both developmental defects and", "both developmental defects and immunodeficiency", "defects and immunodeficiency d\u00f6ffinger", "and immunodeficiency d\u00f6ffinger r", "immunodeficiency d\u00f6ffinger r et", "d\u00f6ffinger r et al. 2001", "et al. 2001 hanson", "al. 2001 hanson ep", "2001 hanson ep et", "hanson ep et al. 2008", "ep et al. 2008 .", "et al. 2008 . several", "al. 2008 . several categories", "2008 . several categories of", ". several categories of mutations", "several categories of mutations affecting", "categories of mutations affecting ikbkg", "of mutations affecting ikbkg have", "mutations affecting ikbkg have been", "affecting ikbkg have been reported", "ikbkg have been reported in", "have been reported in humans", "reported in humans d\u00f6ffinger", "in humans d\u00f6ffinger r", "humans d\u00f6ffinger r et", "et al. 2001 vinolo", "al. 2001 vinolo e", "2001 vinolo e et", "vinolo e et al. 2006", "et al. 2006 fusko", "al. 2006 fusko f", "2006 fusko f et", "fusko f et al. 2008", "f et al. 2008 .", "et al. 2008 . the", "al. 2008 . the first", "2008 . the first category", ". the first category of", "the first category of these", "first category of these mutations", "category of these mutations consists", "of these mutations consists of", "these mutations consists of hypomorphic", "mutations consists of hypomorphic mutations", "consists of hypomorphic mutations typically", "of hypomorphic mutations typically involving", "hypomorphic mutations typically involving the", "mutations typically involving the zinc", "typically involving the zinc finger", "involving the zinc finger domain", "the zinc finger domain and", "zinc finger domain and nearby", "finger domain and nearby c", "domain and nearby c terminal", "and nearby c terminal regions", "nearby c terminal regions and", "c terminal regions and causing", "terminal regions and causing hypohidrotic", "regions and causing hypohidrotic ectodermal", "and causing hypohidrotic ectodermal dysplasia", "causing hypohidrotic ectodermal dysplasia with", "hypohidrotic ectodermal dysplasia with immune", "ectodermal dysplasia with immune deficiency", "with immune deficiency hed", "immune deficiency hed id", "hed id in males", "in males jain a", "males jain a et", "jain a et al. 2001", "et al. 2001 shifera", "al. 2001 shifera as", "2001 shifera as 2010", "shifera as 2010 . the", "as 2010 . the second", "2010 . the second category", ". the second category consists", "the second category consists of", "second category consists of amorphic", "category consists of amorphic mutations", "consists of amorphic mutations causing", "of amorphic mutations causing incontinentia", "amorphic mutations causing incontinentia pigmenti", "causing incontinentia pigmenti ip", "pigmenti ip in", "ip in females and", "in females and generally", "and generally prenatal", "generally prenatal death in", "death in males aradhya", "in males aradhya s", "males aradhya s et", "aradhya s et al. 2001", "et al. 2001 fusco", "al. 2001 fusco f", "2001 fusco f et", "fusco f et al. 2004", "f et al. 2004 .", "et al. 2004 . the", "al. 2004 . the third", "2004 . the third category", ". the third category is", "the third category is composed", "third category is composed of", "category is composed of hypomorphic", "is composed of hypomorphic mutations", "composed of hypomorphic mutations involving", "of hypomorphic mutations involving the", "hypomorphic mutations involving the stop", "mutations involving the stop codon", "involving the stop codon causing", "the stop codon causing anhidrotic", "stop codon causing anhidrotic ectodermal", "codon causing anhidrotic ectodermal dysplasia", "causing anhidrotic ectodermal dysplasia with", "eda id osteopetrosis", "id osteopetrosis and", "osteopetrosis and lymphedema ol", "and lymphedema ol eda", "lymphedema ol eda id", "ol eda id in", "eda id in males", "in males d\u00f6ffinger r", "males d\u00f6ffinger r et", "r et al. 2001 .", "et al. 2001 . also", "al. 2001 . also some", "2001 . also some patients", ". also some patients with", "also some patients with a", "some patients with a defective", "patients with a defective ikbkg", "with a defective ikbkg gene", "a defective ikbkg gene can", "defective ikbkg gene can develop", "ikbkg gene can develop immunodeficiency", "gene can develop immunodeficiency without", "can develop immunodeficiency without ectodermal", "develop immunodeficiency without ectodermal dysplasia", "without ectodermal dysplasia orange", "ectodermal dysplasia orange js", "dysplasia orange js et", "orange js et al. 2004", "js et al. 2004 .", "et al. 2004 . this", "al. 2004 . this module", "2004 . this module describes", ". this module describes several", "this module describes several eda", "module describes several eda id", "describes several eda id associated", "several eda id associated hypomorphic", "eda id associated hypomorphic ikbkg", "id associated hypomorphic ikbkg mutations", "associated hypomorphic ikbkg mutations that", "hypomorphic ikbkg mutations that have", "ikbkg mutations that have been", "mutations that have been reported", "that have been reported to", "have been reported to affect", "been reported to affect inflammatory", "reported to affect inflammatory responses", "to affect inflammatory responses initiated", "affect inflammatory responses initiated by", "inflammatory responses initiated by toll", "responses initiated by toll like", "initiated by toll like receptors", "toll like receptors tlr", "like receptors tlr ." ] }, { "record_id": "GLY_000594_1_447", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5603029", "r hsa", "hsa 5603029", "r hsa 5603029" ] }, { "record_id": "GLY_000594_1_447", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ikba variant", "variant leads", "leads to", "to eda", "eda id", "ikba variant leads", "variant leads to", "leads to eda", "to eda id", "ikba variant leads to", "variant leads to eda", "leads to eda id", "ikba variant leads to eda", "variant leads to eda id", "the nuclear", "nuclear factor", "factor kappa", "kappa b", "family of", "of transcription", "transcription factors", "factors is", "is kept", "kept inactive", "inactive in", "in the", "the cytoplasm", "cytoplasm by", "by the", "the inhibitor", "inhibitor of", "of kappa", "family members", "members ikba", "ikb alpha", "ikb beta", "and ikbe", "ikb epsilon", "oeckinghaus a", "a and", "and ghosh", "ghosh s", "s 2009", "2009 .", ". multiple", "multiple stimuli", "stimuli such", "such as", "as inflammatory", "inflammatory cytokines", "microbial products", "products or", "or various", "various types", "types of", "of stress", "stress 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alkalay", "alkalay i et", "i et al.", "1995 lawrence", "lawrence t 2009", "2009 hoesel", "hoesel b and", "b and schmid", "and schmid ja", "schmid ja 2013", "ja 2013 .", "2013 . the", ". the phosphorylation", "the phosphorylation of", "of ikb proteins", "ikb proteins triggers", "proteins triggers their", "triggers their polyubiquitination", "their polyubiquitination and", "polyubiquitination and subsequent", "and subsequent degradation", "subsequent degradation by", "degradation by 26s", "by 26s proteasome", "proteasome allowing", "allowing free nfkb", "free nfkb dimer", "nfkb dimer to", "dimer to translocate", "to translocate to", "translocate to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it directs", "it directs the", "directs the expression", "the expression of", "expression of target", "of target genes.", "target genes. studies", "genes. studies have", "studies have identified", "have identified an", "identified an autosomal", "an autosomal dominant", "autosomal dominant form", "dominant form of", "form of ectodermal", "of ectodermal dysplasia", "ectodermal dysplasia with", "dysplasia with immunodeficiency", "immunodeficiency ad", "ad eda id", "id caused", "caused by a", "by a hypermorphic", "a hypermorphic heterozygous", "hypermorphic heterozygous mutation", "heterozygous mutation of", "mutation of nfkbia/ikba", "of nfkbia/ikba gene.", "nfkbia/ikba gene. the", "gene. the ikba", "the ikba defects", "ikba defects prevent", "defects prevent the", "prevent the phosphorylation", "the phosphorylation and", "phosphorylation and degradation", "and degradation of", "degradation of ikba", "of ikba protein", "ikba protein resulting", "protein resulting in", "resulting in gain", "in gain of", "gain of function", "of function condition", "function condition with", "condition with the", "with the enhanced", "the enhanced inhibitory", "enhanced inhibitory capacity", "inhibitory capacity of", "capacity of ikba", "of ikba in", "ikba in sequestering", "in sequestering nf?b", "sequestering nf?b dimers", "nf?b dimers in", "dimers in the", "cytoplasm courtois", "courtois g et", "g et al.", "et al. 2003", "2003 lopes", "lopes granados e", "granados e et", "e et al.", "et al. 2008", "2008 schimke", "schimke lf et", "lf et al.", "et al. 2013", "al. 2013 .", "the nuclear factor kappa", "nuclear factor kappa b", "kappa b nfkb", "nfkb family of", "family of transcription factors", "of transcription factors is", "transcription factors is kept", "factors is kept inactive", "is kept inactive in", "kept inactive in the", "inactive in the cytoplasm", "in the cytoplasm by", "the cytoplasm by the", "cytoplasm by the inhibitor", "by the inhibitor of", "the inhibitor of kappa", "inhibitor of kappa b", "kappa b ikb", "ikb family members", "members ikba ikb", "ikba ikb alpha", "ikb alpha nfkbia", "nfkbia ikbb", "ikbb ikb beta", "ikb beta nfkbib", "nfkbib and ikbe", "and ikbe ikb", "ikbe ikb epsilon", "ikb epsilon nfkbie", "nfkbie oeckinghaus", "oeckinghaus a and ghosh", "a and ghosh s", "and ghosh s 2009", "ghosh s 2009 .", "s 2009 . multiple", "2009 . multiple stimuli", ". multiple stimuli such", "multiple stimuli such as", "stimuli such as inflammatory", "such as inflammatory cytokines", "inflammatory cytokines microbial", "cytokines microbial products", "microbial products or various", "products or various types", "or various types of", "various types of stress", "types of stress activate", "of stress activate nfkb", "stress activate nfkb signaling", "activate nfkb signaling leading", "nfkb signaling leading to", "signaling leading to stimuli", "leading to stimuli induced", "to stimuli induced phosphorylation", "stimuli induced phosphorylation of", "induced phosphorylation of ikb", "phosphorylation of ikb molecule", "ikb molecule scherer", "molecule scherer dc", "scherer dc et al.", "dc et al. 1995", "al. 1995 alkalay", "1995 alkalay i", "alkalay i et al.", "i et al. 1995", "al. 1995 lawrence", "1995 lawrence t", "t 2009 hoesel", "2009 hoesel b", "hoesel b and schmid", "b and schmid ja", "and schmid ja 2013", "schmid ja 2013 .", "ja 2013 . the", "2013 . the phosphorylation", ". the phosphorylation of", "the phosphorylation of ikb", "phosphorylation of ikb proteins", "of ikb proteins triggers", "ikb proteins triggers their", "proteins triggers their polyubiquitination", "triggers their polyubiquitination and", "their polyubiquitination and subsequent", "polyubiquitination and subsequent degradation", "and subsequent degradation by", "subsequent degradation by 26s", "degradation by 26s proteasome", "26s proteasome allowing", "proteasome allowing free", "allowing free nfkb dimer", "free nfkb dimer to", "nfkb dimer to translocate", "dimer to translocate to", "to translocate to the", "translocate to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it directs", "where it directs the", "it directs the expression", "directs the expression of", "the expression of target", "expression of target genes.", "of target genes. studies", "target genes. studies have", "genes. studies have identified", "studies have identified an", "have identified an autosomal", "identified an autosomal dominant", "an autosomal dominant form", "autosomal dominant form of", "dominant form of ectodermal", "form of ectodermal dysplasia", "of ectodermal dysplasia with", "ectodermal dysplasia with immunodeficiency", "with immunodeficiency ad", "immunodeficiency ad eda", "eda id caused", "id caused by", "caused by a hypermorphic", "by a hypermorphic heterozygous", "a hypermorphic heterozygous mutation", "hypermorphic heterozygous mutation of", "heterozygous mutation of nfkbia/ikba", "mutation of nfkbia/ikba gene.", "of nfkbia/ikba gene. the", "nfkbia/ikba gene. the ikba", "gene. the ikba defects", "the ikba defects prevent", "ikba defects prevent the", "defects prevent the phosphorylation", "prevent the phosphorylation and", "the phosphorylation and degradation", "phosphorylation and degradation of", "and degradation of ikba", "degradation of ikba protein", "of ikba protein resulting", "ikba protein resulting in", "protein resulting in gain", "resulting in gain of", "in gain of function", "gain of function condition", "of function condition with", "function condition with the", "condition with the enhanced", "with the enhanced inhibitory", "the enhanced inhibitory capacity", "enhanced inhibitory capacity of", "inhibitory capacity of ikba", "capacity of ikba in", "of ikba in sequestering", "ikba in sequestering nf?b", "in sequestering nf?b dimers", "sequestering nf?b dimers in", "nf?b dimers in the", "dimers in the cytoplasm", "the cytoplasm courtois", "cytoplasm courtois g", "courtois g et al.", "g et al. 2003", "al. 2003 lopes", "2003 lopes granados", "lopes granados e et", "granados e et al.", "e et al. 2008", "al. 2008 schimke", "2008 schimke lf", "schimke lf et al.", "lf et al. 2013", "et al. 2013 .", "the nuclear factor kappa b", "factor kappa b nfkb", "b nfkb family", "nfkb family of transcription", "family of transcription factors is", "of transcription factors is kept", "transcription factors is kept inactive", "factors is kept inactive in", "is kept inactive in the", "kept inactive in the cytoplasm", "inactive in the cytoplasm by", "in the cytoplasm by the", "the cytoplasm by the inhibitor", "cytoplasm by the inhibitor of", "by the inhibitor of kappa", "the inhibitor of kappa b", "of kappa b ikb", "b ikb family", "ikb family members ikba", "family members ikba ikb", "members ikba ikb alpha", "beta nfkbib and", "and ikbe ikb epsilon", "nfkbie oeckinghaus a", "oeckinghaus a and ghosh s", "a and ghosh s 2009", "and ghosh s 2009 .", "ghosh s 2009 . multiple", "s 2009 . multiple stimuli", "2009 . multiple stimuli such", ". multiple stimuli such as", "multiple stimuli such as inflammatory", "stimuli such as inflammatory cytokines", "as inflammatory cytokines microbial", "inflammatory cytokines microbial products", "cytokines microbial products or", "microbial products or various types", "products or various types of", "or various types of stress", "various types of stress activate", "types of stress activate nfkb", "of stress activate nfkb signaling", "stress activate nfkb signaling leading", "activate nfkb signaling leading to", "nfkb signaling leading to stimuli", "signaling leading to stimuli induced", "leading to stimuli induced phosphorylation", "to stimuli induced phosphorylation of", "stimuli induced phosphorylation of ikb", "induced phosphorylation of ikb molecule", "of ikb molecule scherer", "ikb molecule scherer dc", "molecule scherer dc et", "scherer dc et al. 1995", "et al. 1995 alkalay", "al. 1995 alkalay i", "1995 alkalay i et", "alkalay i et al. 1995", "et al. 1995 lawrence", "al. 1995 lawrence t", "1995 lawrence t 2009", "lawrence t 2009 hoesel", "t 2009 hoesel b", "2009 hoesel b and", "hoesel b and schmid ja", "b and schmid ja 2013", "and schmid ja 2013 .", "schmid ja 2013 . the", "ja 2013 . the phosphorylation", "2013 . the phosphorylation of", ". the phosphorylation of ikb", "the phosphorylation of ikb proteins", "phosphorylation of ikb proteins triggers", "of ikb proteins triggers their", "ikb proteins triggers their polyubiquitination", "proteins triggers their polyubiquitination and", "triggers their polyubiquitination and subsequent", "their polyubiquitination and subsequent degradation", "polyubiquitination and subsequent degradation by", "and subsequent degradation by 26s", "subsequent degradation by 26s proteasome", "by 26s proteasome allowing", "26s proteasome allowing free", "proteasome allowing free nfkb", "allowing free nfkb dimer to", "free nfkb dimer to translocate", "nfkb dimer to translocate to", "dimer to translocate to the", "to translocate to the nucleus", "translocate to the nucleus where", "to the nucleus where it", "the nucleus where it directs", "nucleus where it directs the", "where it directs the expression", "it directs the expression of", "directs the expression of target", "the expression of target genes.", "expression of target genes. studies", "of target genes. studies have", "target genes. studies have identified", "genes. studies have identified an", "studies have identified an autosomal", "have identified an autosomal dominant", "identified an autosomal dominant form", "an autosomal dominant form of", "autosomal dominant form of ectodermal", "dominant form of ectodermal dysplasia", "form of ectodermal dysplasia with", "of ectodermal dysplasia with immunodeficiency", "dysplasia with immunodeficiency ad", "with immunodeficiency ad eda", "immunodeficiency ad eda id", "ad eda id caused", "eda id caused by", "id caused by a", "caused by a hypermorphic heterozygous", "by a hypermorphic heterozygous mutation", "a hypermorphic heterozygous mutation of", "hypermorphic heterozygous mutation of nfkbia/ikba", "heterozygous mutation of nfkbia/ikba gene.", "mutation of nfkbia/ikba gene. the", "of nfkbia/ikba gene. the ikba", "nfkbia/ikba gene. the ikba defects", "gene. the ikba defects prevent", "the ikba defects prevent the", "ikba defects prevent the phosphorylation", "defects prevent the phosphorylation and", "prevent the phosphorylation and degradation", "the phosphorylation and degradation of", "phosphorylation and degradation of ikba", "and degradation of ikba protein", "degradation of ikba protein resulting", "of ikba protein resulting in", "ikba protein resulting in gain", "protein resulting in gain of", "resulting in gain of function", "in gain of function condition", "gain of function condition with", "of function condition with the", "function condition with the enhanced", "condition with the enhanced inhibitory", "with the enhanced inhibitory capacity", "the enhanced inhibitory capacity of", "enhanced inhibitory capacity of ikba", "inhibitory capacity of ikba in", "capacity of ikba in sequestering", "of ikba in sequestering nf?b", "ikba in sequestering nf?b dimers", "in sequestering nf?b dimers in", "sequestering nf?b dimers in the", "nf?b dimers in the cytoplasm", "in the cytoplasm courtois", "the cytoplasm courtois g", "cytoplasm courtois g et", "courtois g et al. 2003", "et al. 2003 lopes", "al. 2003 lopes granados", "2003 lopes granados e", "lopes granados e et al.", "granados e et al. 2008", "et al. 2008 schimke", "al. 2008 schimke lf", "2008 schimke lf et", "schimke lf et al. 2013", "lf et al. 2013 ." ] }, { "record_id": "GLY_000594_1_448", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5603041", "r hsa", "hsa 5603041", "r hsa 5603041" ] }, { "record_id": "GLY_000594_1_448", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak4 deficiency", "deficiency tlr2/4", "irak4 deficiency tlr2/4", "interleukin 1", "1 receptor", "receptor associated", "associated kinase", "kinase 4", "is a", "a serine/threonine", "serine/threonine kinase", "that mediates", "mediates activation", "activation of", "of transcriptional", "transcriptional factors", "factors such", "such as", "as nfkb", "nfkb and", "and ap1", "ap1 downstream", "downstream of", "of il", "il 1", "1 receptors", "receptors and", "and all", "all toll", "toll like", "like receptors", "except for", "for tlr3", "suzuki n", "n et", "et al.", "al. 2002", "2002 .", ". irak4", "irak4 is", "is recruited", "recruited to", "to the", "the tlr", "tlr receptor", "receptor complex", "complex through", "through a", "a homophilic", "homophilic interaction", "interaction of", "of the", "the death", "death domains", "domains of", "of irak4", "irak4 and", "and adaptor", "adaptor myeloid", "myeloid differentiation", "differentiation factor", "factor 88", "88 protein", "motshwene pg", "pg et", "al. 2009", "lin sc", "sc et", "al. 2010", "2010 .", ". studies", "studies have", "have identified", "identified patients", "patients with", "with an", "an autosomal", "autosomal recessive", "form of", "a health", "health condition", "condition with", "with clinical", "clinical manifestation", "manifestation in", "in infancy", "infancy or", "or early", "early childhood", "that predisposes", "predisposes affected", "affected patients", "patients to", "to recurrent", "recurrent pyogenic", "pyogenic bacterial", "bacterial infection", "streptococcus pneumoniae", "pneumoniae and", "and staphylococcus", "staphylococcus aureus", "picard c", "c et", "al. 2003", "ku cl", "cl et", "al. 2007", "al. 2011", "2011 .", ". leukocytes", "leukocytes derived", "derived from", "from irak4", "irak4 deficient", "deficient patients", "patients display", "display a", "a lack", "lack of", "of production", "production of", "of inflammatory", "inflammatory cytokines", "cytokines such", "as tnf", "tnf alpha", "il 6", "6 and", "and il", "1 beta", "beta by", "by whole", "whole blood", "blood or", "or a", "of cd62", "cd62 ligand", "shedding from", "from granulocytes", "granulocytes following", "following activation", "activation with", "with the", "the most", "most tlr", "tlr agonists", "agonists including", "including those", "those of", "of tlr1/2", "and tlr4", "mcdonald dr", "dr et", "al. 2006", "2007 .", ". however", "lps induced", "induced tlr4", "tlr4 mediated", "mediated production", "of some", "some cytokines", "il8 and", "and mip", "mip 1beta", "was reduced", "reduced but", "but not", "not abolished", ". lps", "lps stimulated", "stimulated induction", "induction of", "of type", "type i", "i ifn", "ifn via", "via myd88", "myd88 irak4", "irak4 independent", "independent signaling", "signaling axis", "axis was", "was normal", "normal or", "or weakly", "weakly affected", "affected suggesting", "suggesting that", "that tlr4", "tlr4 could", "could induce", "induce some", "some responses", "responses in", "in irak4", "patients yang", "yang k", "k et", "al. 2005", "2005 .

patients", ".

patients with", "with ar", "ar irak4", "deficiency were", "were found", "found to", "to bear", "bear homozygous", "homozygous or", "or compound", "compound heterozygous", "heterozygous mutations", "mutations in", "in the", "the irak4", "irak4 gene", "2006 .", ". here", "here we", "we describe", "describe selected", "selected mutations", "that have", "have been", "been functionally", "functionally characterized.", "characterized. cell", "cell based", "based assay", "assay as", "as well", "well as", "as in", "in vitro", "vitro protein", "protein interaction", "interaction analyses", "analyses with", "with irak4", "irak4 variants", "variants showed", "showed that", "that the", "the loss", "loss of", "of function", "function of", "of defective", "defective irak4", "is caused", "caused by", "by either", "either loss", "of protein", "protein production", "reported for", "for irak4", "irak4 q293*", "q293* and", "and e402*", "or an", "an impaired", "impaired interaction", "interaction with", "with myd88", "myd88 as", "as shown", "shown for", "for missense", "missense mutation", "mutation irak4", "irak4 r12c", "yamamoto t", "t et", "al. 2014", "2014 .

besides", ".

besides defective", "defective tlr2/4", "tlr2/4 mediated", "mediated signaling", "the reactome", "reactome module", "module describes", "describes the", "the impact", "impact of", "of functional", "functional deficiency", "deficiency of", "irak4 on", "on tlr5", "tlr5 pathways.", "pathways. the", "the module", "module does", "does not", "not include", "include defective", "defective tlr7", "tlr8 and", "and tlr9", "tlr9 signaling", "signaling events", "which are", "are associated", "associated mostly", "mostly with", "with viral", "viral infections", "although studies", "studies using", "using patient", "patient derived", "derived blood", "blood cells", "cells showed", "showed abolished", "abolished cytokine", "cytokine production", "production by", "by peripheral", "peripheral blood", "blood mononuclear", "mononuclear cells", "and lack", "granulocytes in", "in response", "response to", "to tlr7", "tlr7 9", "9 agonists", "von bernuth", "bernuth h", "h et", ". in", "in addition", "addition to", "tlr nfkappab", "nfkappab signaling", "endosomic tlr7", "9 activates", "activates ifn", "ifn alpha/beta", "alpha/beta and", "and ifn", "ifn gamma", "gamma responses", "responses and", "and these", "these are", "are also", "also impaired", "impaired in", "deficient pbmc", "2005 .", ". nevertheless", "gamma production", "production in", "in irak", "irak 4", "4 deficient", "deficient blood", "cells in", "to 9", "9 of", "of 11", "11 viruses", "viruses was", "that irak", "patients may", "may control", "control viral", "infections by", "by tlr7", "9 independent", "independent production", "of ifns", "ifns such", "as irak4", "independent antiviral", "antiviral rigi", "rigi and", "and mda5", "mda5 pathways", ". so", "so it", "it is", "is not", "not yet", "yet possible", "possible to", "to annotate", "annotate a", "a definitive", "definitive molecular", "molecular pathway", "pathway between", "between irak", "4 deficiency", "deficiency and", "and changes", "changes in", "in tlr7", "9 signaling.", "interleukin 1 receptor", "1 receptor associated", "receptor associated kinase", "associated kinase 4", "4 irak4", "is a serine/threonine", "a serine/threonine kinase", "kinase that", "that mediates activation", "mediates activation of", "activation of transcriptional", "of transcriptional factors", "transcriptional factors such", "factors such as", "such as nfkb", "as nfkb and", "nfkb and ap1", "and ap1 downstream", "ap1 downstream of", "downstream of il", "of il 1", "il 1 receptors", "1 receptors and", "receptors and all", "and all toll", "all toll like", "toll like receptors", "receptors tlr", "tlr except", "except for tlr3", "tlr3 suzuki", "suzuki n et", "n et al.", "et al. 2002", "al. 2002 .", "2002 . irak4", ". irak4 is", "irak4 is recruited", "is recruited to", "recruited to the", "to the tlr", "the tlr receptor", "tlr receptor complex", "receptor complex through", "complex through a", "through a homophilic", "a homophilic interaction", "homophilic interaction of", "interaction of the", "of the death", "the death domains", "death domains of", "domains of irak4", "of irak4 and", "irak4 and adaptor", "and adaptor myeloid", "adaptor myeloid differentiation", "myeloid differentiation factor", "differentiation factor 88", "factor 88 protein", "protein myd88", "motshwene pg et", "pg et al.", "et al. 2009", "2009 lin", "lin sc et", "sc et al.", "et al. 2010", "al. 2010 .", "2010 . studies", ". studies have", "studies have identified", "have identified patients", "identified patients with", "patients with an", "with an autosomal", "an autosomal recessive", "recessive ar", "ar form", "form of irak4", "of irak4 deficiency", "deficiency a", "a health condition", "health condition with", "condition with clinical", "with clinical manifestation", "clinical manifestation in", "manifestation in infancy", "in infancy or", "infancy or early", "or early childhood", "childhood that", "that predisposes affected", "predisposes affected patients", "affected patients to", "patients to recurrent", "to recurrent pyogenic", "recurrent pyogenic bacterial", "pyogenic bacterial infection", "infection e.g.", "e.g. streptococcus", "streptococcus pneumoniae and", "pneumoniae and staphylococcus", "and staphylococcus aureus", "picard c et", "c et al.", "et al. 2003", "2003 ku", "ku cl et", "cl et al.", "et al. 2007", "2007 picard", "2010 picard", "et al. 2011", "al. 2011 .", "2011 . leukocytes", ". leukocytes derived", "leukocytes derived from", "derived from irak4", "from irak4 deficient", "irak4 deficient patients", "deficient patients display", "patients display a", "display a lack", "a lack of", "lack of production", "of production of", "production of inflammatory", "of inflammatory cytokines", "inflammatory cytokines such", "cytokines such as", "such as tnf", "as tnf alpha", "alpha il", "il 6 and", "6 and il", "and il 1", "il 1 beta", "1 beta by", "beta by whole", "by whole blood", "whole blood or", "blood or a", "or a lack", "lack of cd62", "of cd62 ligand", "ligand cd62l", "cd62l shedding", "shedding from granulocytes", "from granulocytes following", "granulocytes following activation", "following activation with", "activation with the", "with the most", "the most tlr", "most tlr agonists", "tlr agonists including", "agonists including those", "including those of", "those of tlr1/2", "tlr1/2 pam3csk4", "tlr2/6 pam2csk4", "pam2csk4 and", "tlr4 lps", "2003 mcdonald", "mcdonald dr et", "dr et al.", "et al. 2006", "2006 ku", "al. 2007 .", "2007 . however", "however lps", "lps induced tlr4", "induced tlr4 mediated", "tlr4 mediated production", "mediated production of", "production of some", "of some cytokines", "cytokines il8", "il8 and mip", "and mip 1beta", "1beta was", "was reduced but", "reduced but not", "but not abolished", "abolished ku", "2007 . lps", ". lps stimulated", "lps stimulated induction", "stimulated induction of", "induction of type", "of type i", "type i ifn", "i ifn via", "ifn via myd88", "via myd88 irak4", "myd88 irak4 independent", "irak4 independent signaling", "independent signaling axis", "signaling axis was", "axis was normal", "was normal or", "normal or weakly", "or weakly affected", "weakly affected suggesting", "affected suggesting that", "suggesting that tlr4", "that tlr4 could", "tlr4 could induce", "could induce some", "induce some responses", "some responses in", "responses in irak4", "in irak4 deficient", "deficient patients yang", "patients yang k", "yang k et", "k et al.", "et al. 2005", "al. 2005 .

patients", "2005 .

patients with", ".

patients with ar", "with ar irak4", "ar irak4 deficiency", "irak4 deficiency were", "deficiency were found", "were found to", "found to bear", "to bear homozygous", "bear homozygous or", "homozygous or compound", "or compound heterozygous", "compound heterozygous mutations", "heterozygous mutations in", "mutations in the", "in the irak4", "the irak4 gene", "gene picard", "2007 mcdonald", "al. 2006 .", "2006 . here", ". here we", "here we describe", "we describe selected", "describe selected mutations", "mutations that", "that have been", "have been functionally", "been functionally characterized.", "functionally characterized. cell", "characterized. cell based", "cell based assay", "based assay as", "assay as well", "as well as", "well as in", "as in vitro", "in vitro protein", "vitro protein interaction", "protein interaction analyses", "interaction analyses with", "analyses with irak4", "with irak4 variants", "irak4 variants showed", "variants showed that", "showed that the", "that the loss", "the loss of", "loss of function", "of function of", "function of defective", "of defective irak4", "defective irak4 is", "irak4 is caused", "is caused by", "caused by either", "by either loss", "either loss of", "loss of protein", "of protein production", "production reported", "reported for irak4", "for irak4 q293*", "irak4 q293* and", "q293* and e402*", "e402* or", "or an impaired", "an impaired interaction", "impaired interaction with", "interaction with myd88", "with myd88 as", "myd88 as shown", "as shown for", "shown for missense", "for missense mutation", "missense mutation irak4", "mutation irak4 r12c", "r12c ku", "2007 yamamoto", "yamamoto t et", "t et al.", "et al. 2014", "al. 2014 .

besides", "2014 .

besides defective", ".

besides defective tlr2/4", "defective tlr2/4 mediated", "tlr2/4 mediated signaling", "signaling the", "the reactome module", "reactome module describes", "module describes the", "describes the impact", "the impact of", "impact of functional", "of functional deficiency", "functional deficiency of", "deficiency of irak4", "of irak4 on", "irak4 on tlr5", "on tlr5 pathways.", "tlr5 pathways. the", "pathways. the module", "the module does", "module does not", "does not include", "not include defective", "include defective tlr7", "tlr7 tlr8", "tlr8 and tlr9", "and tlr9 signaling", "tlr9 signaling events", "events which", "which are associated", "are associated mostly", "associated mostly with", "mostly with viral", "with viral infections", "infections although", "although studies using", "studies using patient", "using patient derived", "patient derived blood", "derived blood cells", "blood cells showed", "cells showed abolished", "showed abolished cytokine", "abolished cytokine production", "cytokine production by", "production by peripheral", "by peripheral blood", "peripheral blood mononuclear", "blood mononuclear cells", "cells pbmcs", "pbmcs and", "and lack of", "from granulocytes in", "granulocytes in response", "in response to", "response to tlr7", "to tlr7 9", "tlr7 9 agonists", "agonists mcdonald", "2006 von", "von bernuth h", "bernuth h et", "h et al.", "2007 . in", ". in addition", "in addition to", "addition to the", "the tlr nfkappab", "tlr nfkappab signaling", "nfkappab signaling axis", "axis endosomic", "endosomic tlr7 9", "tlr7 9 activates", "9 activates ifn", "activates ifn alpha/beta", "ifn alpha/beta and", "alpha/beta and ifn", "and ifn gamma", "ifn gamma responses", "gamma responses and", "responses and these", "and these are", "these are also", "are also impaired", "also impaired in", "impaired in irak4", "irak4 deficient pbmc", "pbmc yang", "al. 2005 .", "2005 . nevertheless", "nevertheless ifn", "and gamma", "gamma production in", "production in irak", "in irak 4", "irak 4 deficient", "4 deficient blood", "deficient blood cells", "blood cells in", "cells in response", "response to 9", "to 9 of", "9 of 11", "of 11 viruses", "11 viruses was", "viruses was normal", "suggesting that irak", "that irak 4", "4 deficient patients", "deficient patients may", "patients may control", "may control viral", "control viral infections", "viral infections by", "infections by tlr7", "by tlr7 9", "tlr7 9 independent", "9 independent production", "independent production of", "production of ifns", "of ifns such", "ifns such as", "such as irak4", "as irak4 independent", "irak4 independent antiviral", "independent antiviral rigi", "antiviral rigi and", "rigi and mda5", "and mda5 pathways", "pathways yang", "2005 . so", ". so it", "so it is", "it is not", "is not yet", "not yet possible", "yet possible to", "possible to annotate", "to annotate a", "annotate a definitive", "a definitive molecular", "definitive molecular pathway", "molecular pathway between", "pathway between irak", "between irak 4", "irak 4 deficiency", "4 deficiency and", "deficiency and changes", "and changes in", "changes in tlr7", "in tlr7 9", "tlr7 9 signaling.", "interleukin 1 receptor associated", "1 receptor associated kinase", "receptor associated kinase 4", "kinase 4 irak4", "irak4 is a", "is a serine/threonine kinase", "serine/threonine kinase that", "kinase that mediates", "that mediates activation of", "mediates activation of transcriptional", "activation of transcriptional factors", "of transcriptional factors such", "transcriptional factors such as", "factors such as nfkb", "such as nfkb and", "as nfkb and ap1", "nfkb and ap1 downstream", "and ap1 downstream of", "ap1 downstream of il", "downstream of il 1", "of il 1 receptors", "il 1 receptors and", "1 receptors and all", "receptors and all toll", "and all toll like", "all toll like receptors", "like receptors tlr", "tlr except for", "for tlr3 suzuki", "tlr3 suzuki n", "suzuki n et al.", "n et al. 2002", "et al. 2002 .", "al. 2002 . irak4", "2002 . irak4 is", ". irak4 is recruited", "irak4 is recruited to", "is recruited to the", "recruited to the tlr", "to the tlr receptor", "the tlr receptor complex", "tlr receptor complex through", "receptor complex through a", "complex through a homophilic", "through a homophilic interaction", "a homophilic interaction of", "homophilic interaction of the", "interaction of the death", "of the death domains", "the death domains of", "death domains of irak4", "domains of irak4 and", "of irak4 and adaptor", "irak4 and adaptor myeloid", "and adaptor myeloid differentiation", "adaptor myeloid differentiation factor", "myeloid differentiation factor 88", "differentiation factor 88 protein", "88 protein myd88", "myd88 motshwene", "motshwene pg et al.", "pg et al. 2009", "al. 2009 lin", "2009 lin sc", "lin sc et al.", "sc et al. 2010", "et al. 2010 .", "al. 2010 . studies", "2010 . studies have", ". studies have identified", "studies have identified patients", "have identified patients with", "identified patients with an", "patients with an autosomal", "with an autosomal recessive", "autosomal recessive ar", "ar form of", "form of irak4 deficiency", "irak4 deficiency a", "deficiency a health", "a health condition with", "health condition with clinical", "condition with clinical manifestation", "with clinical manifestation in", "clinical manifestation in infancy", "manifestation in infancy or", "in infancy or early", "infancy or early childhood", "early childhood that", "childhood that predisposes", "that predisposes affected patients", "predisposes affected patients to", "affected patients to recurrent", "patients to recurrent pyogenic", "to recurrent pyogenic bacterial", "recurrent pyogenic bacterial infection", "bacterial infection e.g.", "e.g. streptococcus pneumoniae", "streptococcus pneumoniae and staphylococcus", "pneumoniae and staphylococcus aureus", "aureus picard", "picard c et al.", "c et al. 2003", "al. 2003 ku", "2003 ku cl", "ku cl et al.", "cl et al. 2007", "al. 2007 picard", "2007 picard c", "c et al. 2010", "al. 2010 picard", "2010 picard c", "c et al. 2011", "et al. 2011 .", "al. 2011 . leukocytes", "2011 . leukocytes derived", ". leukocytes derived from", "leukocytes derived from irak4", "derived from irak4 deficient", "from irak4 deficient patients", "irak4 deficient patients display", "deficient patients display a", "patients display a lack", "display a lack of", "a lack of production", "lack of production of", "of production of inflammatory", "production of inflammatory cytokines", "of inflammatory cytokines such", "inflammatory cytokines such as", "cytokines such as tnf", "such as tnf alpha", "tnf alpha il", "alpha il 6", "il 6 and il", "6 and il 1", "and il 1 beta", "il 1 beta by", "1 beta by whole", "beta by whole blood", "by whole blood or", "whole blood or a", "blood or a lack", "or a lack of", "a lack of cd62", "lack of cd62 ligand", "cd62 ligand cd62l", "cd62l shedding from", "shedding from granulocytes following", "from granulocytes following activation", "granulocytes following activation with", "following activation with the", "activation with the most", "with the most tlr", "the most tlr agonists", "most tlr agonists including", "tlr agonists including those", "agonists including those of", "including those of tlr1/2", "of tlr1/2 pam3csk4", "pam3csk4 tlr2/6", "pam2csk4 and tlr4", "and tlr4 lps", "lps picard", "al. 2003 mcdonald", "2003 mcdonald dr", "mcdonald dr et al.", "dr et al. 2006", "al. 2006 ku", "2006 ku cl", "et al. 2007 .", "al. 2007 . however", ". however lps", "however lps induced", "lps induced tlr4 mediated", "induced tlr4 mediated production", "tlr4 mediated production of", "mediated production of some", "production of some cytokines", "some cytokines il8", "cytokines il8 and", "il8 and mip 1beta", "mip 1beta was", "1beta was reduced", "was reduced but not", "reduced but not abolished", "not abolished ku", "abolished ku cl", "al. 2007 . lps", "2007 . lps stimulated", ". lps stimulated induction", "lps stimulated induction of", "stimulated induction of type", "induction of type i", "of type i ifn", "type i ifn via", "i ifn via myd88", "ifn via myd88 irak4", "via myd88 irak4 independent", "myd88 irak4 independent signaling", "irak4 independent signaling axis", "independent signaling axis was", "signaling axis was normal", "axis was normal or", "was normal or weakly", "normal or weakly affected", "or weakly affected suggesting", "weakly affected suggesting that", "affected suggesting that tlr4", "suggesting that tlr4 could", "that tlr4 could induce", "tlr4 could induce some", "could induce some responses", "induce some responses in", "some responses in irak4", "responses in irak4 deficient", "in irak4 deficient patients", "irak4 deficient patients yang", "deficient patients yang k", "patients yang k et", "yang k et al.", "k et al. 2005", "et al. 2005 .

patients", "al. 2005 .

patients with", "2005 .

patients with ar", ".

patients with ar irak4", "with ar irak4 deficiency", "ar irak4 deficiency were", "irak4 deficiency were found", "deficiency were found to", "were found to bear", "found to bear homozygous", "to bear homozygous or", "bear homozygous or compound", "homozygous or compound heterozygous", "or compound heterozygous mutations", "compound heterozygous mutations in", "heterozygous mutations in the", "mutations in the irak4", "in the irak4 gene", "irak4 gene picard", "gene picard c", "al. 2007 mcdonald", "2007 mcdonald dr", "et al. 2006 .", "al. 2006 . here", "2006 . here we", ". here we describe", "here we describe selected", "we describe selected mutations", "selected mutations that", "mutations that have", "that have been functionally", "have been functionally characterized.", "been functionally characterized. cell", "functionally characterized. cell based", "characterized. cell based assay", "cell based assay as", "based assay as well", "assay as well as", "as well as in", "well as in vitro", "as in vitro protein", "in vitro protein interaction", "vitro protein interaction analyses", "protein interaction analyses with", "interaction analyses with irak4", "analyses with irak4 variants", "with irak4 variants showed", "irak4 variants showed that", "variants showed that the", "showed that the loss", "that the loss of", "the loss of function", "loss of function of", "of function of defective", "function of defective irak4", "of defective irak4 is", "defective irak4 is caused", "irak4 is caused by", "is caused by either", "caused by either loss", "by either loss of", "either loss of protein", "loss of protein production", "protein production reported", "production reported for", "reported for irak4 q293*", "for irak4 q293* and", "irak4 q293* and e402*", "and e402* or", "e402* or an", "or an impaired interaction", "an impaired interaction with", "impaired interaction with myd88", "interaction with myd88 as", "with myd88 as shown", "myd88 as shown for", "as shown for missense", "shown for missense mutation", "for missense mutation irak4", "missense mutation irak4 r12c", "irak4 r12c ku", "r12c ku cl", "al. 2007 yamamoto", "2007 yamamoto t", "yamamoto t et al.", "t et al. 2014", "et al. 2014 .

besides", "al. 2014 .

besides defective", "2014 .

besides defective tlr2/4", ".

besides defective tlr2/4 mediated", "defective tlr2/4 mediated signaling", "mediated signaling the", "signaling the reactome", "the reactome module describes", "reactome module describes the", "module describes the impact", "describes the impact of", "the impact of functional", "impact of functional deficiency", "of functional deficiency of", "functional deficiency of irak4", "deficiency of irak4 on", "of irak4 on tlr5", "irak4 on tlr5 pathways.", "on tlr5 pathways. the", "tlr5 pathways. the module", "pathways. the module does", "the module does not", "module does not include", "does not include defective", "not include defective tlr7", "defective tlr7 tlr8", "tlr7 tlr8 and", "tlr8 and tlr9 signaling", "and tlr9 signaling events", "signaling events which", "events which are", "which are associated mostly", "are associated mostly with", "associated mostly with viral", "mostly with viral infections", "viral infections although", "infections although studies", "although studies using patient", "studies using patient derived", "using patient derived blood", "patient derived blood cells", "derived blood cells showed", "blood cells showed abolished", "cells showed abolished cytokine", "showed abolished cytokine production", "abolished cytokine production by", "cytokine production by peripheral", "production by peripheral blood", "by peripheral blood mononuclear", "peripheral blood mononuclear cells", "mononuclear cells pbmcs", "pbmcs and lack", "and lack of cd62", "shedding from granulocytes in", "from granulocytes in response", "granulocytes in response to", "in response to tlr7", "response to tlr7 9", "to tlr7 9 agonists", "9 agonists mcdonald", "agonists mcdonald dr", "al. 2006 von", "2006 von bernuth", "von bernuth h et", "bernuth h et al.", "h et al. 2006", "al. 2007 . in", "2007 . in addition", ". in addition to", "in addition to the", "addition to the tlr", "to the tlr nfkappab", "the tlr nfkappab signaling", "tlr nfkappab signaling axis", "signaling axis endosomic", "axis endosomic tlr7", "endosomic tlr7 9 activates", "tlr7 9 activates ifn", "9 activates ifn alpha/beta", "activates ifn alpha/beta and", "ifn alpha/beta and ifn", "alpha/beta and ifn gamma", "and ifn gamma responses", "ifn gamma responses and", "gamma responses and these", "responses and these are", "and these are also", "these are also impaired", "are also impaired in", "also impaired in irak4", "impaired in irak4 deficient", "in irak4 deficient pbmc", "deficient pbmc yang", "pbmc yang k", "et al. 2005 .", "al. 2005 . nevertheless", ". nevertheless ifn", "nevertheless ifn alpha/beta", "alpha/beta and gamma", "and gamma production", "gamma production in irak", "production in irak 4", "in irak 4 deficient", "irak 4 deficient blood", "4 deficient blood cells", "deficient blood cells in", "blood cells in response", "cells in response to", "in response to 9", "response to 9 of", "to 9 of 11", "9 of 11 viruses", "of 11 viruses was", "11 viruses was normal", "viruses was normal or", "suggesting that irak 4", "that irak 4 deficient", "irak 4 deficient patients", "4 deficient patients may", "deficient patients may control", "patients may control viral", "may control viral infections", "control viral infections by", "viral infections by tlr7", "infections by tlr7 9", "by tlr7 9 independent", "tlr7 9 independent production", "9 independent production of", "independent production of ifns", "production of ifns such", "of ifns such as", "ifns such as irak4", "such as irak4 independent", "as irak4 independent antiviral", "irak4 independent antiviral rigi", "independent antiviral rigi and", "antiviral rigi and mda5", "rigi and mda5 pathways", "mda5 pathways yang", "pathways yang k", "al. 2005 . so", "2005 . so it", ". so it is", "so it is not", "it is not yet", "is not yet possible", "not yet possible to", "yet possible to annotate", "possible to annotate a", "to annotate a definitive", "annotate a definitive molecular", "a definitive molecular pathway", "definitive molecular pathway between", "molecular pathway between irak", "pathway between irak 4", "between irak 4 deficiency", "irak 4 deficiency and", "4 deficiency and changes", "deficiency and changes in", "and changes in tlr7", "changes in tlr7 9", "in tlr7 9 signaling.", "interleukin 1 receptor associated kinase", "1 receptor associated kinase 4", "associated kinase 4 irak4", "4 irak4 is", "irak4 is a serine/threonine", "a serine/threonine kinase that", "serine/threonine kinase that mediates", "kinase that mediates activation", "that mediates activation of transcriptional", "mediates activation of transcriptional factors", "activation of transcriptional factors such", "of transcriptional factors such as", "transcriptional factors such as nfkb", "factors such as nfkb and", "such as nfkb and ap1", "as nfkb and ap1 downstream", "nfkb and ap1 downstream of", "and ap1 downstream of il", "ap1 downstream of il 1", "downstream of il 1 receptors", "of il 1 receptors and", "il 1 receptors and all", "1 receptors and all toll", "receptors and all toll like", "and all toll like receptors", "toll like receptors tlr", "receptors tlr except", "tlr except for tlr3", "except for tlr3 suzuki", "for tlr3 suzuki n", "tlr3 suzuki n et", "suzuki n et al. 2002", "n et al. 2002 .", "et al. 2002 . irak4", "al. 2002 . irak4 is", "2002 . irak4 is recruited", ". irak4 is recruited to", "irak4 is recruited to the", "is recruited to the tlr", "recruited to the tlr receptor", "to the tlr receptor complex", "the tlr receptor complex through", "tlr receptor complex through a", "receptor complex through a homophilic", "complex through a homophilic interaction", "through a homophilic interaction of", "a homophilic interaction of the", "homophilic interaction of the death", "interaction of the death domains", "of the death domains of", "the death domains of irak4", "death domains of irak4 and", "domains of irak4 and adaptor", "of irak4 and adaptor myeloid", "irak4 and adaptor myeloid differentiation", "and adaptor myeloid differentiation factor", "adaptor myeloid differentiation factor 88", "myeloid differentiation factor 88 protein", "factor 88 protein myd88", "myd88 motshwene pg", "motshwene pg et al. 2009", "et al. 2009 lin", "al. 2009 lin sc", "2009 lin sc et", "lin sc et al. 2010", "sc et al. 2010 .", "et al. 2010 . studies", "al. 2010 . studies have", "2010 . studies have identified", ". studies have identified patients", "studies have identified patients with", "have identified patients with an", "identified patients with an autosomal", "patients with an autosomal recessive", "an autosomal recessive ar", "recessive ar form", "ar form of irak4", "of irak4 deficiency a", "irak4 deficiency a health", "deficiency a health condition", "a health condition with clinical", "health condition with clinical manifestation", "condition with clinical manifestation in", "with clinical manifestation in infancy", "clinical manifestation in infancy or", "manifestation in infancy or early", "in infancy or early childhood", "or early childhood that", "early childhood that predisposes", "childhood that predisposes affected", "that predisposes affected patients to", "predisposes affected patients to recurrent", "affected patients to recurrent pyogenic", "patients to recurrent pyogenic bacterial", "to recurrent pyogenic bacterial infection", "pyogenic bacterial infection e.g.", "infection e.g. streptococcus", "e.g. streptococcus pneumoniae and", "streptococcus pneumoniae and staphylococcus aureus", "staphylococcus aureus picard", "aureus picard c", "picard c et al. 2003", "et al. 2003 ku", "al. 2003 ku cl", "2003 ku cl et", "ku cl et al. 2007", "et al. 2007 picard", "al. 2007 picard c", "2007 picard c et", "picard c et al. 2010", "et al. 2010 picard", "al. 2010 picard c", "2010 picard c et", "picard c et al. 2011", "c et al. 2011 .", "et al. 2011 . leukocytes", "al. 2011 . leukocytes derived", "2011 . leukocytes derived from", ". leukocytes derived from irak4", "leukocytes derived from irak4 deficient", "derived from irak4 deficient patients", "from irak4 deficient patients display", "irak4 deficient patients display a", "deficient patients display a lack", "patients display a lack of", "display a lack of production", "a lack of production of", "lack of production of inflammatory", "of production of inflammatory cytokines", "production of inflammatory cytokines such", "of inflammatory cytokines such as", "inflammatory cytokines such as tnf", "cytokines such as tnf alpha", "as tnf alpha il", "tnf alpha il 6", "alpha il 6 and", "il 6 and il 1", "6 and il 1 beta", "and il 1 beta by", "il 1 beta by whole", "1 beta by whole blood", "beta by whole blood or", "by whole blood or a", "whole blood or a lack", "blood or a lack of", "or a lack of cd62", "a lack of cd62 ligand", "of cd62 ligand cd62l", "ligand cd62l shedding", "cd62l shedding from granulocytes", "shedding from granulocytes following activation", "from granulocytes following activation with", "granulocytes following activation with the", "following activation with the most", "activation with the most tlr", "with the most tlr agonists", "the most tlr agonists including", "most tlr agonists including those", "tlr agonists including those of", "agonists including those of tlr1/2", "those of tlr1/2 pam3csk4", "tlr2/6 pam2csk4 and", "lps picard c", "et al. 2003 mcdonald", "al. 2003 mcdonald dr", "2003 mcdonald dr et", "mcdonald dr et al. 2006", "et al. 2006 ku", "al. 2006 ku cl", "2006 ku cl et", "cl et al. 2007 .", "et al. 2007 . however", "2007 . however lps", ". however lps induced", "however lps induced tlr4", "lps induced tlr4 mediated production", "induced tlr4 mediated production of", "tlr4 mediated production of some", "mediated production of some cytokines", "of some cytokines il8", "some cytokines il8 and", "cytokines il8 and mip", "and mip 1beta was", "mip 1beta was reduced", "1beta was reduced but", "was reduced but not abolished", "but not abolished ku", "not abolished ku cl", "abolished ku cl et", "et al. 2007 . lps", "al. 2007 . lps stimulated", "2007 . lps stimulated induction", ". lps stimulated induction of", "lps stimulated induction of type", "stimulated induction of type i", "induction of type i ifn", "of type i ifn via", "type i ifn via myd88", "i ifn via myd88 irak4", "ifn via myd88 irak4 independent", "via myd88 irak4 independent signaling", "myd88 irak4 independent signaling axis", "irak4 independent signaling axis was", "independent signaling axis was normal", "signaling axis was normal or", "axis was normal or weakly", "was normal or weakly affected", "normal or weakly affected suggesting", "or weakly affected suggesting that", "weakly affected suggesting that tlr4", "affected suggesting that tlr4 could", "suggesting that tlr4 could induce", "that tlr4 could induce some", "tlr4 could induce some responses", "could induce some responses in", "induce some responses in irak4", "some responses in irak4 deficient", "responses in irak4 deficient patients", "in irak4 deficient patients yang", "irak4 deficient patients yang k", "deficient patients yang k et", "patients yang k et al.", "yang k et al. 2005", "k et al. 2005 .

patients", "et al. 2005 .

patients with", "al. 2005 .

patients with ar", "2005 .

patients with ar irak4", ".

patients with ar irak4 deficiency", "with ar irak4 deficiency were", "ar irak4 deficiency were found", "irak4 deficiency were found to", "deficiency were found to bear", "were found to bear homozygous", "found to bear homozygous or", "to bear homozygous or compound", "bear homozygous or compound heterozygous", "homozygous or compound heterozygous mutations", "or compound heterozygous mutations in", "compound heterozygous mutations in the", "heterozygous mutations in the irak4", "mutations in the irak4 gene", "the irak4 gene picard", "irak4 gene picard c", "gene picard c et", "et al. 2007 mcdonald", "al. 2007 mcdonald dr", "2007 mcdonald dr et", "dr et al. 2006 .", "et al. 2006 . here", "al. 2006 . here we", "2006 . here we describe", ". here we describe selected", "here we describe selected mutations", "describe selected mutations that", "selected mutations that have", "mutations that have been", "that have been functionally characterized.", "have been functionally characterized. cell", "been functionally characterized. cell based", "functionally characterized. cell based assay", "characterized. cell based assay as", "cell based assay as well", "based assay as well as", "assay as well as in", "as well as in vitro", "well as in vitro protein", "as in vitro protein interaction", "in vitro protein interaction analyses", "vitro protein interaction analyses with", "protein interaction analyses with irak4", "interaction analyses with irak4 variants", "analyses with irak4 variants showed", "with irak4 variants showed that", "irak4 variants showed that the", "variants showed that the loss", "showed that the loss of", "that the loss of function", "the loss of function of", "loss of function of defective", "of function of defective irak4", "function of defective irak4 is", "of defective irak4 is caused", "defective irak4 is caused by", "irak4 is caused by either", "is caused by either loss", "caused by either loss of", "by either loss of protein", "either loss of protein production", "of protein production reported", "protein production reported for", "production reported for irak4", "reported for irak4 q293* and", "for irak4 q293* and e402*", "q293* and e402* or", "and e402* or an", "e402* or an impaired", "or an impaired interaction with", "an impaired interaction with myd88", "impaired interaction with myd88 as", "interaction with myd88 as shown", "with myd88 as shown for", "myd88 as shown for missense", "as shown for missense mutation", "shown for missense mutation irak4", "for missense mutation irak4 r12c", "mutation irak4 r12c ku", "irak4 r12c ku cl", "r12c ku cl et", "et al. 2007 yamamoto", "al. 2007 yamamoto t", "2007 yamamoto t et", "yamamoto t et al. 2014", "t et al. 2014 .

besides", "et al. 2014 .

besides defective", "al. 2014 .

besides defective tlr2/4", "2014 .

besides defective tlr2/4 mediated", ".

besides defective tlr2/4 mediated signaling", "tlr2/4 mediated signaling the", "mediated signaling the reactome", "signaling the reactome module", "the reactome module describes the", "reactome module describes the impact", "module describes the impact of", "describes the impact of functional", "the impact of functional deficiency", "impact of functional deficiency of", "of functional deficiency of irak4", "functional deficiency of irak4 on", "deficiency of irak4 on tlr5", "of irak4 on tlr5 pathways.", "irak4 on tlr5 pathways. the", "on tlr5 pathways. the module", "tlr5 pathways. the module does", "pathways. the module does not", "the module does not include", "module does not include defective", "does not include defective tlr7", "include defective tlr7 tlr8", "defective tlr7 tlr8 and", "tlr7 tlr8 and tlr9", "tlr8 and tlr9 signaling events", "tlr9 signaling events which", "signaling events which are", "events which are associated", "which are associated mostly with", "are associated mostly with viral", "associated mostly with viral infections", "with viral infections although", "viral infections although studies", "infections although studies using", "although studies using patient derived", "studies using patient derived blood", "using patient derived blood cells", "patient derived blood cells showed", "derived blood cells showed abolished", "blood cells showed abolished cytokine", "cells showed abolished cytokine production", "showed abolished cytokine production by", "abolished cytokine production by peripheral", "cytokine production by peripheral blood", "production by peripheral blood mononuclear", "by peripheral blood mononuclear cells", "blood mononuclear cells pbmcs", "cells pbmcs and", "pbmcs and lack of", "and lack of cd62 ligand", "shedding from granulocytes in response", "from granulocytes in response to", "granulocytes in response to tlr7", "in response to tlr7 9", "response to tlr7 9 agonists", "tlr7 9 agonists mcdonald", "9 agonists mcdonald dr", "agonists mcdonald dr et", "et al. 2006 von", "al. 2006 von bernuth", "2006 von bernuth h", "von bernuth h et al.", "bernuth h et al. 2006", "et al. 2007 . in", "al. 2007 . in addition", "2007 . in addition to", ". in addition to the", "in addition to the tlr", "addition to the tlr nfkappab", "to the tlr nfkappab signaling", "the tlr nfkappab signaling axis", "nfkappab signaling axis endosomic", "signaling axis endosomic tlr7", "axis endosomic tlr7 9", "endosomic tlr7 9 activates ifn", "tlr7 9 activates ifn alpha/beta", "9 activates ifn alpha/beta and", "activates ifn alpha/beta and ifn", "ifn alpha/beta and ifn gamma", "alpha/beta and ifn gamma responses", "and ifn gamma responses and", "ifn gamma responses and these", "gamma responses and these are", "responses and these are also", "and these are also impaired", "these are also impaired in", "are also impaired in irak4", "also impaired in irak4 deficient", "impaired in irak4 deficient pbmc", "irak4 deficient pbmc yang", "deficient pbmc yang k", "pbmc yang k et", "k et al. 2005 .", "et al. 2005 . nevertheless", "2005 . nevertheless ifn", ". nevertheless ifn alpha/beta", "nevertheless ifn alpha/beta and", "ifn alpha/beta and gamma", "alpha/beta and gamma production", "and gamma production in", "gamma production in irak 4", "production in irak 4 deficient", "in irak 4 deficient blood", "irak 4 deficient blood cells", "4 deficient blood cells in", "deficient blood cells in response", "blood cells in response to", "cells in response to 9", "in response to 9 of", "response to 9 of 11", "to 9 of 11 viruses", "9 of 11 viruses was", "of 11 viruses was normal", "11 viruses was normal or", "viruses was normal or weakly", "affected suggesting that irak", "suggesting that irak 4 deficient", "that irak 4 deficient patients", "irak 4 deficient patients may", "4 deficient patients may control", "deficient patients may control viral", "patients may control viral infections", "may control viral infections by", "control viral infections by tlr7", "viral infections by tlr7 9", "infections by tlr7 9 independent", "by tlr7 9 independent production", "tlr7 9 independent production of", "9 independent production of ifns", "independent production of ifns such", "production of ifns such as", "of ifns such as irak4", "ifns such as irak4 independent", "such as irak4 independent antiviral", "as irak4 independent antiviral rigi", "irak4 independent antiviral rigi and", "independent antiviral rigi and mda5", "antiviral rigi and mda5 pathways", "and mda5 pathways yang", "mda5 pathways yang k", "pathways yang k et", "et al. 2005 . so", "al. 2005 . so it", "2005 . so it is", ". so it is not", "so it is not yet", "it is not yet possible", "is not yet possible to", "not yet possible to annotate", "yet possible to annotate a", "possible to annotate a definitive", "to annotate a definitive molecular", "annotate a definitive molecular pathway", "a definitive molecular pathway between", "definitive molecular pathway between irak", "molecular pathway between irak 4", "pathway between irak 4 deficiency", "between irak 4 deficiency and", "irak 4 deficiency and changes", "4 deficiency and changes in", "deficiency and changes in tlr7", "and changes in tlr7 9", "changes in tlr7 9 signaling." ] }, { "record_id": "GLY_000594_1_449", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5607761", "r hsa", "hsa 5607761", "r hsa 5607761" ] }, { "record_id": "GLY_000594_1_449", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dectin 1", "1 mediated", "mediated noncanonical", "noncanonical nf", "nf kb", "kb signaling", "dectin 1 mediated", "1 mediated noncanonical", "mediated noncanonical nf", "noncanonical nf kb", "nf kb signaling", "dectin 1 mediated noncanonical", "1 mediated noncanonical nf", "mediated noncanonical nf kb", "noncanonical nf kb signaling", "dectin 1 mediated noncanonical nf", "1 mediated noncanonical nf kb", 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"sustained several hours", "several hours longer", "hours longer than", "longer than does", "than does the", "does the activation", "canonical nf kb.", "nf kb. the", "kb. the noncanonical", "the noncanonical nf", "kb pathway is", "pathway is characterized", "is characterized by", "characterized by the", "by the post", "the post translational", "post translational processing", "translational processing of", "processing of nfkb2", "nfkb2 nuclear", "nuclear factor nf", "factor nf kappa", "nf kappa b", "b p100", "p100 subunit to", "subunit to the", "to the mature", "the mature p52", "mature p52 subunit.", "p52 subunit. this", "subunit. this subsequently", "this subsequently leads", "subsequently leads to", "leads to nuclear", "to nuclear translocation", "translocation of p52:relb", "p52:relb transcription", "transcription factor relb", "relb complexes", "complexes to induce", "to induce cytokine", "induce cytokine expression", "cytokine expression of", "expression of some", "of some genes", "genes c", "c c motif", "c motif chemokine", "motif chemokine 17", "17 ccl17", "ccl17 and", "ccl22 and", "and transcriptional repression", "transcriptional repression of", "repression of others", "others il12b", "2009 geijtenbeek", "2009 plato", "plato et al.", "et al. 2013", "al. 2013 .", "in addition to the", "addition to the activation", "to the activation of", "the activation of canonical", "activation of canonical nf", "of canonical nf kb", "canonical nf kb subunits", "kb subunits activation", "subunits activation of", "activation of syk pathway", "of syk pathway by", "syk pathway by dectin", "pathway by dectin 1", "by dectin 1 leads", "dectin 1 leads to", "1 leads to the", "leads to the induction", "to the induction of", "the induction of the", "induction of the non", "of the non canonical", "the non canonical nf", "non canonical nf kb", "canonical nf kb pathway", "kb pathway which", "pathway which mediates", "which mediates the nuclear", "mediates the nuclear 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.", "2009 . these", ". these cellular", "these cellular responses", "cellular responses mediated", "responses mediated by", "mediated by clec7a", "by clec7a rely", "clec7a rely on", "rely on both", "on both syk", "both syk dependent", "syk dependent and", "dependent and syk", "and syk independent", "syk independent signaling", "independent signaling cascades.", "signaling cascades. the", "cascades. the pathways", "the pathways leading", "pathways leading to", "leading to the", "to the syk", "the syk dependent", "syk dependent activation", "dependent activation of", "activation of nf", "of nf kb", "nf kb can", "kb can be", "can be categorised", "be categorised into", "categorised into both", "into both canonical", "both canonical and", "canonical and non", "and non canonical", "non canonical routes", "routes gringhuis", "gringhuis et al.", "2009 . activation", ". activation of", "activation of the", "of the canonical", "the canonical nf", "canonical nf kb", "nf kb pathway", "kb pathway 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"human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5617472", "r hsa", "hsa 5617472", "r hsa 5617472" ] }, { "record_id": "GLY_000594_1_454", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of anterior", "anterior hox", "hox genes", "genes in", "in hindbrain", "hindbrain development", "development during", "during early", "early embryogenesis", "activation of anterior", "of anterior hox", "anterior hox genes", "hox genes in", "genes in hindbrain", "in hindbrain development", "hindbrain development during", "development during early", "during early embryogenesis", "activation of anterior hox", "of anterior hox genes", "anterior hox genes in", "hox genes in hindbrain", "genes in hindbrain development", "in hindbrain development during", "hindbrain development during early", "development during early embryogenesis", "activation of anterior hox genes", "of anterior hox genes in", "anterior hox 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hoxa1", ".
hoxa1 appears", "appears to", "to set", "set the", "the anterior", "anterior limit", "limit of", "of hoxb1", "hoxb1 expression", "barrow et", "al. 2000", "2000 .", ". hoxb1", "hoxb1 initiates", "initiates expression", "of egr2", "presumptive r3.", "r3. egr2", "egr2 then", "then activates", "activates hoxa2", "hoxa2 expression", "in r3", "and r5", "r5 while", "while hoxb1", "together with", "pbx1 and", "and meis:pknox1", "activates expression", "of hoxa2", "hoxa2 in", "in r4", "r4 and", "and caudal", "caudal rhombomeres.", "ap 2", "2 transcription", "transcription factors", "factors maintain", "maintain expression", "in neural", "neural crest", "crest cells", "maconochie et", "1999 .", "hoxb1 also", "also activates", "of hoxb2", "hoxb2 in", "rhombomeres. egr2", "egr2 negatively", "negatively regulates", "regulates hoxb1", "hoxb1 so", "so that", "that by", "the time", "time rhombomeres", "rhombomeres appear", "is restricted", "restricted to", "to r4", "and hoxa1", "hoxa1 is", "is no", "no longer", "longer detectable", ". egr2", "egr2 and", "and mafb", "then activate", "activate hoxa3", "hoxa3 and", "and hoxb3", "hoxb3 in", "rhombomeres. retinoic", "acid activates", "activates hoxa4", "and hoxd4", "hoxd4 in", "in r7", "the final", "final rhombomere.", "rhombomere. hox", "hox proteins", "in turn", "activate expression", "of genes", "in combination", "combination with", "with other", "other factors", "notably members", "members of", "the tale", "tale family", "family of", "of transcription", "and meis", "in schulte", "schulte and", "and frank", "frank 2014", "rezsohazy et", "al. 2015", "2015 .", "proteins also", "also participate", "participate in", "in non", "non transcriptional", "transcriptional interactions", "in rezsohazy", "rezsohazy 2014", ". in", "in zebrafish", "and chicken", "chicken factors", "factors such", "such as", "as meis3", "and vhnf", "vhnf regulate", "regulate anterior", "however less", "less is", "is known", "known about", "about the", "the roles", "roles of", "of homologous", "homologous factors", "factors in", "in mammals.
", "mammals.
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prior to", ".
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hoxa1", "2013 .
hoxa1 appears", ".
hoxa1 appears to", "appears to set", "to set the", "set the anterior", "the anterior limit", "anterior limit of", "limit of hoxb1", "of hoxb1 expression", "expression barrow", "barrow et al.", "et al. 2000", "al. 2000 .", "2000 . hoxb1", ". hoxb1 initiates", "hoxb1 initiates expression", "initiates expression of", "expression of egr2", "egr2 krox20", "krox20 in", "in presumptive r3.", "presumptive r3. egr2", "r3. egr2 then", "egr2 then activates", "then activates hoxa2", "activates hoxa2 expression", "hoxa2 expression in", "expression in r3", "in r3 and", "r3 and r5", "and r5 while", "r5 while hoxb1", "hoxb1 together", "together with pbx1", "with pbx1 and", "pbx1 and meis:pknox1", "meis:pknox1 meis:prep", "activates expression of", "expression of hoxa2", "of hoxa2 in", "hoxa2 in r4", "in r4 and", "r4 and caudal", "and caudal rhombomeres.", "rhombomeres. ap", "ap 2 transcription", "2 transcription factors", "transcription factors maintain", "factors maintain expression", "maintain expression of", "hoxa2 in neural", "in neural crest", "neural crest cells", "cells maconochie", "maconochie et al.", "al. 1999 .", "1999 . hoxb1", ". hoxb1 also", "hoxb1 also activates", "also activates expression", "expression of hoxb2", "of hoxb2 in", "hoxb2 in r3", "r3 and caudal", "caudal rhombomeres. egr2", "rhombomeres. egr2 negatively", "egr2 negatively regulates", "negatively regulates hoxb1", "regulates hoxb1 so", "hoxb1 so that", "so that by", "that by the", "by the time", "the time rhombomeres", "time rhombomeres appear", "appear hoxb1", "hoxb1 is restricted", "is restricted to", "restricted to r4", "to r4 and", "r4 and hoxa1", "and hoxa1 is", "hoxa1 is no", "is no longer", "no longer detectable", "detectable barrow", "2000 . egr2", ". egr2 and", "egr2 and mafb", "mafb kreisler", "kreisler then", "then activate hoxa3", "activate hoxa3 and", "hoxa3 and hoxb3", "and hoxb3 in", "hoxb3 in r5", "r5 and caudal", "caudal rhombomeres. retinoic", "rhombomeres. retinoic acid", "retinoic acid activates", "acid activates hoxa4", "hoxa4 hoxb4", "hoxb4 and", "and hoxd4 in", "hoxd4 in r7", "r7 the", "the final rhombomere.", "final rhombomere. hox", "rhombomere. hox proteins", "proteins in", "turn activate", "activate expression of", "expression of genes", "of genes in", "genes in combination", "in combination with", "combination with other", "with other factors", "factors notably", "notably members of", "members of the", "of the tale", "the tale family", "tale family of", "family of transcription", "of transcription factors", "factors pbx", "pbx prep", "prep and", "meis reviewed", "reviewed in schulte", "in schulte and", "schulte and frank", "and frank 2014", "2014 rezsohazy", "rezsohazy et al.", "et al. 2015", "al. 2015 .", "2015 . hox", ". hox proteins", "hox proteins also", "proteins also participate", "also participate in", "participate in non", "in non transcriptional", "non transcriptional interactions", "interactions reviewed", "reviewed in rezsohazy", "in rezsohazy 2014", "rezsohazy 2014 .", "2014 . in", ". in zebrafish", "zebrafish xenopus", "xenopus and", "and chicken factors", "chicken factors such", "factors such as", "such as meis3", "meis3 fgf3", "fgf3 fgf8", "fgf8 and", "and vhnf regulate", "vhnf regulate anterior", "regulate anterior hox", "genes reviewed", "however less is", "less is known", "is known about", "known about the", "about the roles", "the roles of", "roles of homologous", "of homologous factors", "homologous factors in", "factors in mammals.
", "in mammals.
mutations", "mammals.
mutations in", "mutations in hoxa1", "in hoxa1 in", "hoxa1 in humans", "in humans have", "humans have been", "have been observed", "been observed to", "observed to cause", "to cause developmental", "cause developmental abnormalities", "developmental abnormalities located", "abnormalities located mostly", "located mostly in", "mostly in the", "in the head", "the head and", "head and neck", "and neck region", "region tischfield", "tischfield et al.", "et al. 2005", "2005 bosley", "bosley et al.", "et al. 2008", "al. 2008 .", "2008 . a", ". a missense", "a missense mutation", "missense mutation in", "mutation in hoxa2", "in hoxa2 causes", "hoxa2 causes microtia", "microtia hearing", "impairment and", "and partially cleft", "partially cleft palate", "palate alasti", "alasti et al.", "mutation in hoxb1", "in hoxb1 causes", "hoxb1 causes a", "causes a similar", "a similar phenotype", "similar phenotype to", "phenotype to the", "to the hoxb1", "the hoxb1 null", "hoxb1 null mutation", "null mutation in", "mutation in mice:", "in mice: bilateral", "mice: bilateral facial", "bilateral facial palsy", "palsy hearing", "loss and", "strabismus improper", "improper alignment of", "alignment of the", "of the eyes", "webb et al.", "et al. 2012", "al. 2012 .", "in mammals anterior", "mammals anterior hox", "anterior hox genes may", "hox genes may be", "genes may be defined", "may be defined as", "be defined as paralog", "defined as paralog groups", "as paralog groups 1", "paralog groups 1 to", "groups 1 to 4", "to 4 natale", "4 natale et", "natale et al. 2011", "2011 which", "which are involved in", "are involved in development", "involved in development of", "in development of the", "development of the hindbrain", "of the hindbrain through", "the hindbrain through sequential", "hindbrain through sequential expression", "through sequential expression in", "sequential expression in the", "expression in the rhombomeres", "the rhombomeres transient", "rhombomeres transient segments", "transient segments of the", "segments of the neural", "of the neural tube", "the neural tube that", "neural tube that form", "tube that form during", "that form during development", "form during development of", "during development of the", "the hindbrain reviewed", "hindbrain reviewed in", "reviewed in alexander et", "in alexander et al.", "alexander et al. 2009", "al. 2009 soshnikova", "2009 soshnikova and", "soshnikova and duboule 2009", "duboule 2009 tumpel", "2009 tumpel et", "tumpel et al. 2009", "al. 2009 mallo", "2009 mallo et", "mallo et al. 2010", "al. 2010 andrey", "2010 andrey and", "andrey and duboule 2014", "and duboule 2014 .", "duboule 2014 . hox", "2014 . hox gene", ". hox gene activation", "hox gene activation during", "gene activation during mammalian", "activation during mammalian development", "during mammalian development has", "mammalian development has been", "development has been most", "has been most thoroughly", "been most thoroughly studied", "most thoroughly studied in", "thoroughly studied in mouse", "studied in mouse embryos", "in mouse embryos and", "mouse embryos and the", "embryos and the results", "and the results have", "the results have been", "results have been extended", "have been extended to", "been extended to human", "extended to human development", "to human development by", "human development by in", "development by in vitro", "by in vitro experiments", "in vitro experiments with", "vitro experiments with human", "experiments with human embryonal", "with human embryonal carcinoma", "human embryonal carcinoma cells", "embryonal carcinoma cells and", "carcinoma cells and human", "cells and human embryonic", "and human embryonic stem", "human embryonic stem cells.
expression", "embryonic stem cells.
expression of", "stem cells.
expression of a", "cells.
expression of a typical", "of a typical anterior", "a typical anterior hox", "typical anterior hox gene", "anterior hox gene has", "hox gene has an", "gene has an anterior", "has an anterior boundary", "an anterior boundary located", "anterior boundary located at", "boundary located at the", "located at the junction", "at the junction between", "the junction between two", "junction between two rhombomeres", "between two rhombomeres and", "two rhombomeres and continues", "rhombomeres and continues caudally", "and continues caudally to", "continues caudally to regulate", "caudally to regulate segmentation", "to regulate segmentation and", "regulate segmentation and segmental", "segmentation and segmental fate", "and segmental fate in", "segmental fate in ectoderm", "in ectoderm mesoderm", "mesoderm and endoderm.", "and endoderm. anterior boundaries", "endoderm. anterior boundaries of", "anterior boundaries of expression", "boundaries of expression of", "of expression of successive", "expression of successive hox", "of successive hox paralog", "successive hox paralog groups", "hox paralog groups are", "paralog groups are generally", "groups are generally separated", "are generally separated from", "generally separated from each", "separated from each other", "from each other by", "each other by 2", "other by 2 rhombomeres.", "by 2 rhombomeres. for", "2 rhombomeres. for example", "for example hoxb2", "example hoxb2 is", "hoxb2 is expressed in", "is expressed in rhombomere", "expressed in rhombomere 3", "rhombomere 3 r3", "and caudally while hoxb3", "caudally while hoxb3 is", "while hoxb3 is expressed", "hoxb3 is expressed in", "is expressed in r5", "expressed in r5 and", "in r5 and caudally.", "r5 and caudally. exceptions", "and caudally. exceptions exist", "exceptions exist however", "however as hoxa1", "as hoxa1 hoxa2", "hoxa2 and hoxb1", "and hoxb1 do not", "hoxb1 do not follow", "do not follow the", "not follow the rule", "follow the rule and", "the rule and hoxd1", "rule and hoxd1 and", "and hoxd1 and hoxc4", "hoxd1 and hoxc4 are", "and hoxc4 are not", "hoxc4 are not expressed", "are not expressed in", "not expressed in rhombomeres.", "expressed in rhombomeres. hox", "in rhombomeres. hox genes", "rhombomeres. hox genes within", "hox genes within a", "genes within a hox", "within a hox cluster", "a hox cluster are", "hox cluster are expressed", "cluster are expressed colinearly:", "are expressed colinearly: the", "expressed colinearly: the gene", "colinearly: the gene at", "the gene at the", "gene at the 3'", "at the 3' end", "the 3' end of", "3' end of the", "end of the cluster", "of the cluster is", "the cluster is expressed", "cluster is expressed earliest", "expressed earliest and", "earliest and hence", "and hence most anteriorly", "most anteriorly then", "anteriorly then genes", "then genes 5' are", "genes 5' are activated", "5' are activated sequentially", "are activated sequentially in", "activated sequentially in the", "sequentially in the same", "in the same order", "the same order as", "same order as they", "order as they occur", "as they occur in", "they occur in the", "occur in the cluster.", "in the cluster.
activation", "the cluster.
activation of", "cluster.
activation of expression", "
activation of expression occurs", "of expression occurs epigenetically", "expression occurs epigenetically by", "occurs epigenetically by loss", "epigenetically by loss of", "by loss of polycomb", "loss of polycomb repressive", "of polycomb repressive complexes", "polycomb repressive complexes and", "repressive complexes and change", "complexes and change of", "and change of bivalent", "change of bivalent chromatin", "of bivalent chromatin to", "bivalent chromatin to active", "chromatin to active chromatin", "to active chromatin through", "chromatin through in", "through in part", "in part the", "part the actions", "the actions of trithorax", "actions of trithorax family", "of trithorax family proteins", "family proteins reviewed", "proteins reviewed in", "reviewed in soshnikova and", "in soshnikova and duboule", "and duboule 2009 .", "duboule 2009 . hox", "2009 . hox gene", ". hox gene expression", "hox gene expression initiates", "gene expression initiates in", "expression initiates in the", "initiates in the posterior", "in the posterior primitive", "the posterior primitive streak", "posterior primitive streak that", "primitive streak that will", "streak that will contribute", "that will contribute to", "will contribute to extraembryonic", "contribute to extraembryonic mesoderm.", "to extraembryonic mesoderm. expression", "extraembryonic mesoderm. expression then", "mesoderm. expression then extends", "expression then extends anteriorly", "then extends anteriorly into", "extends anteriorly into the", "anteriorly into the cells", "into the cells that", "the cells that will", "cells that will become", "that will become the", "will become the embryo", "the embryo where", "embryo where expression", "where expression is first", "expression is first observed", "is first observed in", "first observed in presumptive", "observed in presumptive lateral", "in presumptive lateral plate", "presumptive lateral plate mesoderm", "lateral plate mesoderm and", "plate mesoderm and is", "mesoderm and is transmitted", "and is transmitted to", "is transmitted to both", "transmitted to both paraxial", "to both paraxial mesoderm", "both paraxial mesoderm and", "paraxial mesoderm and neurectoderm", "mesoderm and neurectoderm formed", "and neurectoderm formed by", "neurectoderm formed by gastrulation", "formed by gastrulation along", "by gastrulation along the", "gastrulation along the primitive", "along the primitive streak", "primitive streak reviewed", "streak reviewed in", "reviewed in deschamps et", "in deschamps et al.", "deschamps et al. 1999", "al. 1999 casaca", "1999 casaca et", "casaca et al. 2014", "et al. 2014 .
prior", "al. 2014 .
prior to", "2014 .
prior to establishment", ".
prior to establishment of", "to establishment of the", "establishment of the rhombomeres", "the rhombomeres expression", "rhombomeres expression of", "expression of hoxa1 and", "of hoxa1 and hoxb1", "hoxa1 and hoxb1 is", "and hoxb1 is initiated", "hoxb1 is initiated near", "is initiated near the", "initiated near the future", "near the future site", "the future site of", "future site of r3", "site of r3 and", "of r3 and caudally", "r3 and caudally by", "and caudally by a", "caudally by a gradient", "by a gradient of", "a gradient of retinoic", "gradient of retinoic acid", "retinoic acid ra", "acid ra .", "ra . mechanisms", ". mechanisms of", "mechanisms of retinoic acid", "of retinoic acid signaling", "retinoic acid signaling are", "acid signaling are reviewed", "signaling are reviewed in", "are reviewed in cunningham", "reviewed in cunningham and", "in cunningham and duester", "cunningham and duester 2015.", "duester 2015. the", "2015. the ra", "the ra is generated", "ra is generated by", "is generated by the", "generated by the aldh1a2", "the aldh1a2 raldh2", "raldh2 enzyme located", "enzyme located in somites", "located in somites flanking", "in somites flanking the", "somites flanking the caudal", "flanking the caudal hindbrain", "the caudal hindbrain and", "caudal hindbrain and degraded", "hindbrain and degraded by", "and degraded by cyp26", "degraded by cyp26 enzymes", "by cyp26 enzymes expressed", "cyp26 enzymes expressed initially", "enzymes expressed initially in", "expressed initially in anterior", "initially in anterior neural", "in anterior neural ectoderm", "anterior neural ectoderm of", "neural ectoderm of the", "ectoderm of the early", "of the early gastrula", "the early gastrula and", "early gastrula and then", "gastrula and then throughout", "and then throughout most", "then throughout most of", "throughout most of the", "most of the hindbrain", "reviewed in white and", "in white and schilling", "white and schilling 2008", "and schilling 2008 .", "schilling 2008 . hoxa1", "2008 . hoxa1 with", ". hoxa1 with pbx1", "hoxa1 with pbx1 2", "with pbx1 2 and", "pbx1 2 and meis2", "2 and meis2 directly", "and meis2 directly activate", "meis2 directly activate transcription", "directly activate transcription of", "activate transcription of aldh1a2", "transcription of aldh1a2 to", "of aldh1a2 to maintain", "aldh1a2 to maintain retinoic", "to maintain retinoic acid", "maintain retinoic acid synthesis", "retinoic acid synthesis in", "acid synthesis in the", "synthesis in the somitic", "in the somitic mesoderm", "somitic mesoderm vitobello", "mesoderm vitobello et", "vitobello et al. 2011", "et al. 2011 .", "al. 2011 . differentiation", "2011 . differentiation of", ". differentiation of embryonal", "differentiation of embryonal carcinoma", "of embryonal carcinoma cells", "carcinoma cells and embryonic", "cells and embryonic stem", "and embryonic stem cells", "embryonic stem cells in", "stem cells in response", "cells in response to", "in response to retinoic", "response to retinoic acid", "to retinoic acid is", "retinoic acid is used", "acid is used to", "is used to model", "used to model the", "to model the process", "model the process of", "the process of differentiation", "process of differentiation in", "of differentiation in vitro", "in vitro reviewed", "vitro reviewed in", "reviewed in soprano et", "in soprano et al.", "soprano et al. 2007", "al. 2007 gudas", "2007 gudas et", "gudas et al. 2013", "et al. 2013 .
hoxa1", "al. 2013 .
hoxa1 appears", "2013 .
hoxa1 appears to", ".
hoxa1 appears to set", "appears to set the", "to set the anterior", "set the anterior limit", "the anterior limit of", "anterior limit of hoxb1", "limit of hoxb1 expression", "hoxb1 expression barrow", "expression barrow et", "barrow et al. 2000", "et al. 2000 .", "al. 2000 . hoxb1", "2000 . hoxb1 initiates", ". hoxb1 initiates expression", "hoxb1 initiates expression of", "initiates expression of egr2", "of egr2 krox20", "krox20 in presumptive", "in presumptive r3. egr2", "presumptive r3. egr2 then", "r3. egr2 then activates", "egr2 then activates hoxa2", "then activates hoxa2 expression", "activates hoxa2 expression in", "hoxa2 expression in r3", "expression in r3 and", "in r3 and r5", "r3 and r5 while", "and r5 while hoxb1", "while hoxb1 together", "hoxb1 together with", "together with pbx1 and", "with pbx1 and meis:pknox1", "and meis:pknox1 meis:prep", "meis:prep activates", "activates expression of hoxa2", "expression of hoxa2 in", "of hoxa2 in r4", "hoxa2 in r4 and", "in r4 and caudal", "r4 and caudal rhombomeres.", "caudal rhombomeres. ap", "rhombomeres. ap 2", "ap 2 transcription factors", "2 transcription factors maintain", "transcription factors maintain expression", "factors maintain expression of", "maintain expression of hoxa2", "of hoxa2 in neural", "hoxa2 in neural crest", "in neural crest cells", "crest cells maconochie", "cells maconochie et", "maconochie et al. 1999", "et al. 1999 .", "al. 1999 . hoxb1", "1999 . hoxb1 also", ". hoxb1 also activates", "hoxb1 also activates expression", "also activates expression of", "activates expression of hoxb2", "expression of hoxb2 in", "of hoxb2 in r3", "hoxb2 in r3 and", "in r3 and caudal", "r3 and caudal rhombomeres.", "and caudal rhombomeres. egr2", "caudal rhombomeres. egr2 negatively", "rhombomeres. egr2 negatively regulates", "egr2 negatively regulates hoxb1", "negatively regulates hoxb1 so", "regulates hoxb1 so that", "hoxb1 so that by", "so that by the", "that by the time", "by the time rhombomeres", "the time rhombomeres appear", "rhombomeres appear hoxb1", "appear hoxb1 is", "hoxb1 is restricted to", "is restricted to r4", "restricted to r4 and", "to r4 and hoxa1", "r4 and hoxa1 is", "and hoxa1 is no", "hoxa1 is no longer", "is no longer detectable", "longer detectable barrow", "detectable barrow et", "al. 2000 . egr2", "2000 . egr2 and", ". egr2 and mafb", "and mafb kreisler", "kreisler then activate", "then activate hoxa3 and", "activate hoxa3 and hoxb3", "hoxa3 and hoxb3 in", "and hoxb3 in r5", "hoxb3 in r5 and", "in r5 and caudal", "r5 and caudal rhombomeres.", "and caudal rhombomeres. retinoic", "caudal rhombomeres. retinoic acid", "rhombomeres. retinoic acid activates", "retinoic acid activates hoxa4", "activates hoxa4 hoxb4", "hoxb4 and hoxd4", "and hoxd4 in r7", "in r7 the", "r7 the final", "the final rhombomere. hox", "final rhombomere. hox proteins", "hox proteins in", "proteins in turn", "in turn activate", "turn activate expression", "activate expression of genes", "expression of genes in", "of genes in combination", "genes in combination with", "in combination with other", "combination with other factors", "other factors notably", "factors notably members", "notably members of the", "members of the tale", "of the tale family", "the tale family of", "tale family of transcription", "family of transcription factors", "transcription factors pbx", "prep and meis", "and meis reviewed", "meis reviewed in", "reviewed in schulte and", "in schulte and frank", "schulte and frank 2014", "frank 2014 rezsohazy", "2014 rezsohazy et", "rezsohazy et al. 2015", "et al. 2015 .", "al. 2015 . hox", "2015 . hox proteins", ". hox proteins also", "hox proteins also participate", "proteins also participate in", "also participate in non", "participate in non transcriptional", "in non transcriptional interactions", "transcriptional interactions reviewed", "interactions reviewed in", "reviewed in rezsohazy 2014", "in rezsohazy 2014 .", "rezsohazy 2014 . in", "2014 . in zebrafish", "in zebrafish xenopus", "xenopus and chicken", "and chicken factors such", "chicken factors such as", "factors such as meis3", "as meis3 fgf3", "fgf8 and vhnf", "and vhnf regulate anterior", "vhnf regulate anterior hox", "regulate anterior hox genes", "hox genes reviewed", "genes reviewed in", "2014 however", "however less is known", "less is known about", "is known about the", "known about the roles", "about the roles of", "the roles of homologous", "roles of homologous factors", "of homologous factors in", "homologous factors in mammals.
", "factors in mammals.
mutations", "in mammals.
mutations in", "mammals.
mutations in hoxa1", "mutations in hoxa1 in", "in hoxa1 in humans", "hoxa1 in humans have", "in humans have been", "humans have been observed", "have been observed to", "been observed to cause", "observed to cause developmental", "to cause developmental abnormalities", "cause developmental abnormalities located", "developmental abnormalities located mostly", "abnormalities located mostly in", "located mostly in the", "mostly in the head", "in the head and", "the head and neck", "head and neck region", "neck region tischfield", "region tischfield et", "tischfield et al. 2005", "al. 2005 bosley", "2005 bosley et", "bosley et al. 2008", "et al. 2008 .", "al. 2008 . a", "2008 . a missense", ". a missense mutation", "a missense mutation in", "missense mutation in hoxa2", "mutation in hoxa2 causes", "in hoxa2 causes microtia", "causes microtia hearing", "microtia hearing impairment", "hearing impairment and", "impairment and partially", "and partially cleft palate", "cleft palate alasti", "palate alasti et", "alasti et al. 2008", "missense mutation in hoxb1", "mutation in hoxb1 causes", "in hoxb1 causes a", "hoxb1 causes a similar", "causes a similar phenotype", "a similar phenotype to", "similar phenotype to the", "phenotype to the hoxb1", "to the hoxb1 null", "the hoxb1 null mutation", "hoxb1 null mutation in", "null mutation in mice:", "mutation in mice: bilateral", "in mice: bilateral facial", "mice: bilateral facial palsy", "facial palsy hearing", "palsy hearing loss", "hearing loss and", "loss and strabismus", "and strabismus improper", "strabismus improper alignment", "improper alignment of the", "alignment of the eyes", "eyes webb", "webb et al. 2012", "et al. 2012 .", "in mammals anterior hox", "mammals anterior hox genes", "anterior hox genes may be", "hox genes may be defined", "genes may be defined as", "may be defined as paralog", "be defined as paralog groups", "defined as paralog groups 1", "as paralog groups 1 to", "paralog groups 1 to 4", "1 to 4 natale", "to 4 natale et", "4 natale et al.", "al. 2011 which", "2011 which are", "which are involved in development", "are involved in development of", "involved in development of the", "in development of the hindbrain", "development of the hindbrain through", "of the hindbrain through sequential", "the hindbrain through sequential expression", "hindbrain through sequential expression in", "through sequential expression in the", "sequential expression in the rhombomeres", "in the rhombomeres transient", "the rhombomeres transient segments", "rhombomeres transient segments of", "transient segments of the neural", "segments of the neural tube", "of the neural tube that", "the neural tube that form", "neural tube that form during", "tube that form during development", "that form during development of", "form during development of the", "during development of the hindbrain", "of the hindbrain reviewed", "the hindbrain reviewed in", "hindbrain reviewed in alexander", "reviewed in alexander et al.", "in alexander et al. 2009", "et al. 2009 soshnikova", "al. 2009 soshnikova and", "2009 soshnikova and duboule", "and duboule 2009 tumpel", "duboule 2009 tumpel et", "2009 tumpel et al.", "et al. 2009 mallo", "al. 2009 mallo et", "2009 mallo et al.", "et al. 2010 andrey", "al. 2010 andrey and", "2010 andrey and duboule", "andrey and duboule 2014 .", "and duboule 2014 . hox", "duboule 2014 . hox gene", "2014 . hox gene activation", ". hox gene activation during", "hox gene activation during mammalian", "gene activation during mammalian development", "activation during mammalian development has", "during mammalian development has been", "mammalian development has been most", "development has been most thoroughly", "has been most thoroughly studied", "been most thoroughly studied in", "most thoroughly studied in mouse", "thoroughly studied in mouse embryos", "studied in mouse embryos and", "in mouse embryos and the", "mouse embryos and the results", "embryos and the results have", "and the results have been", "the results have been extended", "results have been extended to", "have been extended to human", "been extended to human development", "extended to human development by", "to human development by in", "human development by in vitro", "development by in vitro experiments", "by in vitro experiments with", "in vitro experiments with human", "vitro experiments with human embryonal", "experiments with human embryonal carcinoma", "with human embryonal carcinoma cells", "human embryonal carcinoma cells and", "embryonal carcinoma cells and human", "carcinoma cells and human embryonic", "cells and human embryonic stem", "and human embryonic stem cells.
expression", "human embryonic stem cells.
expression of", "embryonic stem cells.
expression of a", "stem cells.
expression of a typical", "cells.
expression of a typical anterior", "of a typical anterior hox", "a typical anterior hox gene", "typical anterior hox gene has", "anterior hox gene has an", "hox gene has an anterior", "gene has an anterior boundary", "has an anterior boundary located", "an anterior boundary located at", "anterior boundary located at the", "boundary located at the junction", "located at the junction between", "at the junction between two", "the junction between two rhombomeres", "junction between two rhombomeres and", "between two rhombomeres and continues", "two rhombomeres and continues caudally", "rhombomeres and continues caudally to", "and continues caudally to regulate", "continues caudally to regulate segmentation", "caudally to regulate segmentation and", "to regulate segmentation and segmental", "regulate segmentation and segmental fate", "segmentation and segmental fate in", "and segmental fate in ectoderm", "fate in ectoderm mesoderm", "ectoderm mesoderm and", "mesoderm and endoderm. anterior", "and endoderm. anterior boundaries of", "endoderm. anterior boundaries of expression", "anterior boundaries of expression of", "boundaries of expression of successive", "of expression of successive hox", "expression of successive hox paralog", "of successive hox paralog groups", "successive hox paralog groups are", "hox paralog groups are generally", "paralog groups are generally separated", "groups are generally separated from", "are generally separated from each", "generally separated from each other", "separated from each other by", "from each other by 2", "each other by 2 rhombomeres.", "other by 2 rhombomeres. for", "by 2 rhombomeres. for example", "rhombomeres. for example hoxb2", "for example hoxb2 is", "example hoxb2 is expressed", "hoxb2 is expressed in rhombomere", "is expressed in rhombomere 3", "in rhombomere 3 r3", "3 r3 and", "r3 and caudally while", "and caudally while hoxb3 is", "caudally while hoxb3 is expressed", "while hoxb3 is expressed in", "hoxb3 is expressed in r5", "is expressed in r5 and", "expressed in r5 and caudally.", "in r5 and caudally. exceptions", "r5 and caudally. exceptions exist", "caudally. exceptions exist however", "exist however as", "hoxa1 hoxa2 and", "hoxa2 and hoxb1 do", "and hoxb1 do not follow", "hoxb1 do not follow the", "do not follow the rule", "not follow the rule and", "follow the rule and hoxd1", "the rule and hoxd1 and", "rule and hoxd1 and hoxc4", "and hoxd1 and hoxc4 are", "hoxd1 and hoxc4 are not", "and hoxc4 are not expressed", "hoxc4 are not expressed in", "are not expressed in rhombomeres.", "not expressed in rhombomeres. hox", "expressed in rhombomeres. hox genes", "in rhombomeres. hox genes within", "rhombomeres. hox genes within a", "hox genes within a hox", "genes within a hox cluster", "within a hox cluster are", "a hox cluster are expressed", "hox cluster are expressed colinearly:", "cluster are expressed colinearly: the", "are expressed colinearly: the gene", "expressed colinearly: the gene at", "colinearly: the gene at the", "the gene at the 3'", "gene at the 3' end", "at the 3' end of", "the 3' end of the", "3' end of the cluster", "end of the cluster is", "of the cluster is expressed", "the cluster is expressed earliest", "is expressed earliest and", "expressed earliest and hence", "earliest and hence most", "hence most anteriorly then", "most anteriorly then genes", "anteriorly then genes 5'", "then genes 5' are activated", "genes 5' are activated sequentially", "5' are activated sequentially in", "are activated sequentially in the", "activated sequentially in the same", "sequentially in the same order", "in the same order as", "the same order as they", "same order as they occur", "order as they occur in", "as they occur in the", "they occur in the cluster.", "occur in the cluster.
activation", "in the cluster.
activation of", "the cluster.
activation of expression", "cluster.
activation of expression occurs", "
activation of expression occurs epigenetically", "of expression occurs epigenetically by", "expression occurs epigenetically by loss", "occurs epigenetically by loss of", "epigenetically by loss of polycomb", "by loss of polycomb repressive", "loss of polycomb repressive complexes", "of polycomb repressive complexes and", "polycomb repressive complexes and change", "repressive complexes and change of", "complexes and change of bivalent", "and change of bivalent chromatin", "change of bivalent chromatin to", "of bivalent chromatin to active", "bivalent chromatin to active chromatin", "chromatin to active chromatin through", "active chromatin through in", "chromatin through in part", "in part the actions", "part the actions of", "the actions of trithorax family", "actions of trithorax family proteins", "trithorax family proteins reviewed", "family proteins reviewed in", "proteins reviewed in soshnikova", "reviewed in soshnikova and duboule", "in soshnikova and duboule 2009", "soshnikova and duboule 2009 .", "and duboule 2009 . hox", "duboule 2009 . hox gene", "2009 . hox gene expression", ". hox gene expression initiates", "hox gene expression initiates in", "gene expression initiates in the", "expression initiates in the posterior", "initiates in the posterior primitive", "in the posterior primitive streak", "the posterior primitive streak that", "posterior primitive streak that will", "primitive streak that will contribute", "streak that will contribute to", "that will contribute to extraembryonic", "will contribute to extraembryonic mesoderm.", "contribute to extraembryonic mesoderm. expression", "to extraembryonic mesoderm. expression then", "extraembryonic mesoderm. expression then extends", "mesoderm. expression then extends anteriorly", "expression then extends anteriorly into", "then extends anteriorly into the", "extends anteriorly into the cells", "anteriorly into the cells that", "into the cells that will", "the cells that will become", "cells that will become the", "that will become the embryo", "become the embryo where", "the embryo where expression", "embryo where expression is", "where expression is first observed", "expression is first observed in", "is first observed in presumptive", "first observed in presumptive lateral", "observed in presumptive lateral plate", "in presumptive lateral plate mesoderm", "presumptive lateral plate mesoderm and", "lateral plate mesoderm and is", "plate mesoderm and is transmitted", "mesoderm and is transmitted to", "and is transmitted to both", "is transmitted to both paraxial", "transmitted to both paraxial mesoderm", "to both paraxial mesoderm and", "both paraxial mesoderm and neurectoderm", "paraxial mesoderm and neurectoderm formed", "mesoderm and neurectoderm formed by", "and neurectoderm formed by gastrulation", "neurectoderm formed by gastrulation along", "formed by gastrulation along the", "by gastrulation along the primitive", "gastrulation along the primitive streak", "the primitive streak reviewed", "primitive streak reviewed in", "streak reviewed in deschamps", "reviewed in deschamps et al.", "in deschamps et al. 1999", "et al. 1999 casaca", "al. 1999 casaca et", "1999 casaca et al.", "casaca et al. 2014 .
prior", "et al. 2014 .
prior to", "al. 2014 .
prior to establishment", "2014 .
prior to establishment of", ".
prior to establishment of the", "to establishment of the rhombomeres", "of the rhombomeres expression", "the rhombomeres expression of", "rhombomeres expression of hoxa1", "expression of hoxa1 and hoxb1", "of hoxa1 and hoxb1 is", "hoxa1 and hoxb1 is initiated", "and hoxb1 is initiated near", "hoxb1 is initiated near the", "is initiated near the future", "initiated near the future site", "near the future site of", "the future site of r3", "future site of r3 and", "site of r3 and caudally", "of r3 and caudally by", "r3 and caudally by a", "and caudally by a gradient", "caudally by a gradient of", "by a gradient of retinoic", "a gradient of retinoic acid", "of retinoic acid ra", "retinoic acid ra .", "ra . mechanisms of", ". mechanisms of retinoic", "mechanisms of retinoic acid signaling", "of retinoic acid signaling are", "retinoic acid signaling are reviewed", "acid signaling are reviewed in", "signaling are reviewed in cunningham", "are reviewed in cunningham and", "reviewed in cunningham and duester", "in cunningham and duester 2015.", "and duester 2015. the", "duester 2015. the ra", "2015. the ra is", "the ra is generated by", "ra is generated by the", "is generated by the aldh1a2", "by the aldh1a2 raldh2", "aldh1a2 raldh2 enzyme", "raldh2 enzyme located in", "enzyme located in somites flanking", "located in somites flanking the", "in somites flanking the caudal", "somites flanking the caudal hindbrain", "flanking the caudal hindbrain and", "the caudal hindbrain and degraded", "caudal hindbrain and degraded by", "hindbrain and degraded by cyp26", "and degraded by cyp26 enzymes", "degraded by cyp26 enzymes expressed", "by cyp26 enzymes expressed initially", "cyp26 enzymes expressed initially in", "enzymes expressed initially in anterior", "expressed initially in anterior neural", "initially in anterior neural ectoderm", "in anterior neural ectoderm of", "anterior neural ectoderm of the", "neural ectoderm of the early", "ectoderm of the early gastrula", "of the early gastrula and", "the early gastrula and then", "early gastrula and then throughout", "gastrula and then throughout most", "and then throughout most of", "then throughout most of the", "throughout most of the hindbrain", "hindbrain reviewed in white", "reviewed in white and schilling", "in white and schilling 2008", "white and schilling 2008 .", "and schilling 2008 . hoxa1", "schilling 2008 . hoxa1 with", "2008 . hoxa1 with pbx1", ". hoxa1 with pbx1 2", "hoxa1 with pbx1 2 and", "with pbx1 2 and meis2", "pbx1 2 and meis2 directly", "2 and meis2 directly activate", "and meis2 directly activate transcription", "meis2 directly activate transcription of", "directly activate transcription of aldh1a2", "activate transcription of aldh1a2 to", "transcription of aldh1a2 to maintain", "of aldh1a2 to maintain retinoic", "aldh1a2 to maintain retinoic acid", "to maintain retinoic acid synthesis", "maintain retinoic acid synthesis in", "retinoic acid synthesis in the", "acid synthesis in the somitic", "synthesis in the somitic mesoderm", "the somitic mesoderm vitobello", "somitic mesoderm vitobello et", "mesoderm vitobello et al.", "vitobello et al. 2011 .", "et al. 2011 . differentiation", "al. 2011 . differentiation of", "2011 . differentiation of embryonal", ". differentiation of embryonal carcinoma", "differentiation of embryonal carcinoma cells", "of embryonal carcinoma cells and", "embryonal carcinoma cells and embryonic", "carcinoma cells and embryonic stem", "cells and embryonic stem cells", "and embryonic stem cells in", "embryonic stem cells in response", "stem cells in response to", "cells in response to retinoic", "in response to retinoic acid", "response to retinoic acid is", "to retinoic acid is used", "retinoic acid is used to", "acid is used to model", "is used to model the", "used to model the process", "to model the process of", "model the process of differentiation", "the process of differentiation in", "process of differentiation in vitro", "differentiation in vitro reviewed", "in vitro reviewed in", "vitro reviewed in soprano", "reviewed in soprano et al.", "in soprano et al. 2007", "et al. 2007 gudas", "al. 2007 gudas et", "2007 gudas et al.", "gudas et al. 2013 .
hoxa1", "et al. 2013 .
hoxa1 appears", "al. 2013 .
hoxa1 appears to", "2013 .
hoxa1 appears to set", ".
hoxa1 appears to set the", "appears to set the anterior", "to set the anterior limit", "set the anterior limit of", "the anterior limit of hoxb1", "anterior limit of hoxb1 expression", "of hoxb1 expression barrow", "hoxb1 expression barrow et", "expression barrow et al.", "barrow et al. 2000 .", "et al. 2000 . hoxb1", "al. 2000 . hoxb1 initiates", "2000 . hoxb1 initiates expression", ". hoxb1 initiates expression of", "hoxb1 initiates expression of egr2", "expression of egr2 krox20", "egr2 krox20 in", "krox20 in presumptive r3.", "in presumptive r3. egr2 then", "presumptive r3. egr2 then activates", "r3. egr2 then activates hoxa2", "egr2 then activates hoxa2 expression", "then activates hoxa2 expression in", "activates hoxa2 expression in r3", "hoxa2 expression in r3 and", "expression in r3 and r5", "in r3 and r5 while", "r3 and r5 while hoxb1", "r5 while hoxb1 together", "while hoxb1 together with", "hoxb1 together with pbx1", "together with pbx1 and meis:pknox1", "pbx1 and meis:pknox1 meis:prep", "meis:prep activates expression", "activates expression of hoxa2 in", "expression of hoxa2 in r4", "of hoxa2 in r4 and", "hoxa2 in r4 and caudal", "in r4 and caudal rhombomeres.", "and caudal rhombomeres. ap", "caudal rhombomeres. ap 2", "rhombomeres. ap 2 transcription", "ap 2 transcription factors maintain", "2 transcription factors maintain expression", "transcription factors maintain expression of", "factors maintain expression of hoxa2", "maintain expression of hoxa2 in", "expression of hoxa2 in neural", "of hoxa2 in neural crest", "hoxa2 in neural crest cells", "neural crest cells maconochie", "crest cells maconochie et", "cells maconochie et al.", "maconochie et al. 1999 .", "et al. 1999 . hoxb1", "al. 1999 . hoxb1 also", "1999 . hoxb1 also activates", ". hoxb1 also activates expression", "hoxb1 also activates expression of", "also activates expression of hoxb2", "activates expression of hoxb2 in", "expression of hoxb2 in r3", "of hoxb2 in r3 and", "hoxb2 in r3 and caudal", "in r3 and caudal rhombomeres.", "r3 and caudal rhombomeres. egr2", "and caudal rhombomeres. egr2 negatively", "caudal rhombomeres. egr2 negatively regulates", "rhombomeres. egr2 negatively regulates hoxb1", "egr2 negatively regulates hoxb1 so", "negatively regulates hoxb1 so that", "regulates hoxb1 so that by", "hoxb1 so that by the", "so that by the time", "that by the time rhombomeres", "by the time rhombomeres appear", "time rhombomeres appear hoxb1", "rhombomeres appear hoxb1 is", "appear hoxb1 is restricted", "hoxb1 is restricted to r4", "is restricted to r4 and", "restricted to r4 and hoxa1", "to r4 and hoxa1 is", "r4 and hoxa1 is no", "and hoxa1 is no longer", "hoxa1 is no longer detectable", "no longer detectable barrow", "longer detectable barrow et", "detectable barrow et al.", "et al. 2000 . egr2", "al. 2000 . egr2 and", "2000 . egr2 and mafb", "egr2 and mafb kreisler", "mafb kreisler then", "kreisler then activate hoxa3", "then activate hoxa3 and hoxb3", "activate hoxa3 and hoxb3 in", "hoxa3 and hoxb3 in r5", "and hoxb3 in r5 and", "hoxb3 in r5 and caudal", "in r5 and caudal rhombomeres.", "r5 and caudal rhombomeres. retinoic", "and caudal rhombomeres. retinoic acid", "caudal rhombomeres. retinoic acid activates", "rhombomeres. retinoic acid activates hoxa4", "acid activates hoxa4 hoxb4", "hoxa4 hoxb4 and", "hoxb4 and hoxd4 in", "hoxd4 in r7 the", "in r7 the final", "r7 the final rhombomere.", "the final rhombomere. hox proteins", "rhombomere. hox proteins in", "hox proteins in turn", "in turn activate expression", "turn activate expression of", "activate expression of genes in", "expression of genes in combination", "of genes in combination with", "genes in combination with other", "in combination with other factors", "with other factors notably", "other factors notably members", "factors notably members of", "notably members of the tale", "members of the tale family", "of the tale family of", "the tale family of transcription", "tale family of transcription factors", "of transcription factors pbx", "factors pbx prep", "pbx prep and", "and meis reviewed in", "meis reviewed in schulte", "reviewed in schulte and frank", "in schulte and frank 2014", "and frank 2014 rezsohazy", "frank 2014 rezsohazy et", "2014 rezsohazy et al.", "rezsohazy et al. 2015 .", "et al. 2015 . hox", "al. 2015 . hox proteins", "2015 . hox proteins also", ". hox proteins also participate", "hox proteins also participate in", "proteins also participate in non", "also participate in non transcriptional", "participate in non transcriptional interactions", "non transcriptional interactions reviewed", "transcriptional interactions reviewed in", "interactions reviewed in rezsohazy", "reviewed in rezsohazy 2014 .", "in rezsohazy 2014 . in", "rezsohazy 2014 . in zebrafish", ". in zebrafish xenopus", "zebrafish xenopus and", "xenopus and chicken factors", "and chicken factors such as", "chicken factors such as meis3", "such as meis3 fgf3", "meis3 fgf3 fgf8", "fgf3 fgf8 and", "fgf8 and vhnf regulate", "and vhnf regulate anterior hox", "vhnf regulate anterior hox genes", "anterior hox genes reviewed", "hox genes reviewed in", "genes reviewed in schulte", "frank 2014 however", "2014 however less", "however less is known about", "less is known about the", "is known about the roles", "known about the roles of", "about the roles of homologous", "the roles of homologous factors", "roles of homologous factors in", "of homologous factors in mammals.
", "homologous factors in mammals.
mutations", "factors in mammals.
mutations in", "in mammals.
mutations in hoxa1", "mammals.
mutations in hoxa1 in", "mutations in hoxa1 in humans", "in hoxa1 in humans have", "hoxa1 in humans have been", "in humans have been observed", "humans have been observed to", "have been observed to cause", "been observed to cause developmental", "observed to cause developmental abnormalities", "to cause developmental abnormalities located", "cause developmental abnormalities located mostly", "developmental abnormalities located mostly in", "abnormalities located mostly in the", "located mostly in the head", "mostly in the head and", "in the head and neck", "the head and neck region", "and neck region tischfield", "neck region tischfield et", "region tischfield et al.", "et al. 2005 bosley", "al. 2005 bosley et", "2005 bosley et al.", "bosley et al. 2008 .", "et al. 2008 . a", "al. 2008 . a missense", "2008 . a missense mutation", ". a missense mutation in", "a missense mutation in hoxa2", "missense mutation in hoxa2 causes", "mutation in hoxa2 causes microtia", "hoxa2 causes microtia hearing", "causes microtia hearing impairment", "hearing impairment and partially", "impairment and partially cleft", "partially cleft palate alasti", "cleft palate alasti et", "palate alasti et al.", "alasti et al. 2008 .", "a missense mutation in hoxb1", "missense mutation in hoxb1 causes", "mutation in hoxb1 causes a", "in hoxb1 causes a similar", "hoxb1 causes a similar phenotype", "causes a similar phenotype to", "a similar phenotype to the", "similar phenotype to the hoxb1", "phenotype to the hoxb1 null", "to the hoxb1 null mutation", "the hoxb1 null mutation in", "hoxb1 null mutation in mice:", "null mutation in mice: bilateral", "mutation in mice: bilateral facial", "in mice: bilateral facial palsy", "bilateral facial palsy hearing", "facial palsy hearing loss", "hearing loss and strabismus", "and strabismus improper alignment", "strabismus improper alignment of", "improper alignment of the eyes", "the eyes webb", "eyes webb et", "webb et al. 2012 ." ] }, { "record_id": "GLY_000594_1_455", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5617833", "r hsa", "hsa 5617833", "r hsa 5617833" ] }, { "record_id": "GLY_000594_1_455", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cilium assembly", "cilia are", "are membrane", "membrane covered", "covered organelles", "organelles that", "that extend", "extend from", "from the", "the surface", "surface of", "of eukaryotic", "eukaryotic cells.", "cells. cilia", "cilia may", "may be", "be motile", "such as", "as respiratory", "respiratory cilia", "or non", "non motile", "as the", "the primary", "primary cilium", "and are", "are distinguished", "distinguished by", "by the", "the structure", "structure of", "of their", "their microtubule", "microtubule based", "based axonemes.", "axonemes. the", "the axoneme", "axoneme consists", "consists of", "of nine", "nine peripheral", "peripheral doublet", "doublet microtubules", "and 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"membrane and the", "and the subsequent", "the subsequent polymerization", "subsequent polymerization of", "polymerization of the", "of the microtubule", "the microtubule based", "microtubule based axoneme", "based axoneme and", "axoneme and extension", "and extension of", "extension of the", "of the plasma", "membrane reviewed", "reviewed in ishikawa", "in ishikawa and", "ishikawa and marshall", "marshall 2011", "2011 reiter", "reiter et al", "2012 . although", ". although the", "although the ciliary", "the ciliary membrane", "ciliary membrane is", "membrane is continuous", "is continuous with", "continuous with the", "with the plasma", "membrane the", "the protein and", "protein and lipid", "and lipid content", "lipid content of", "content of the", "of the cilium", "the cilium and", "cilium and the", "and the ciliary", "ciliary membrane are", "membrane are distinct", "are distinct from", "distinct from those", "from those of", "those of the", "of the bulk", "the bulk cytoplasm", "bulk cytoplasm and", "cytoplasm and plasma", "and plasma membrane", "reviewed in emmer", "in emmer et", "emmer et al", "al 2010", "2010 rohatgi", "rohatgi and snell", "snell 2010", "2010 . this", ". this specialized", "this specialized compartment", "specialized compartment is", "compartment is established", "is established and", "established and maintained", "and maintained during", "maintained during cilium", "during cilium biogenesis", "cilium biogenesis by", "biogenesis by the", "by the formation", "the formation of", "formation of a", "of a ciliary", "a ciliary transition", "ciliary transition zone", "zone a", "a proteinaceous structure", "proteinaceous structure that", "that with", "with the transition", "the transition fibres", "fibres anchors", "anchors the basal", "basal body to", "body to the", "to the plasma", "membrane and acts", "and acts as", "acts as a", "as a ciliary", "a ciliary pore", "ciliary pore to", "pore to limit", "to limit free", "limit free diffusion", "free diffusion from", "diffusion from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the cilium", "cilium reviewed", "reviewed in nachury", "in nachury et", "nachury et al", "2010 reiter", "2012 . ciliary", ". ciliary components", "ciliary components are", "components are targeted", "are targeted from", "targeted from the", "from the secretory", "the secretory system", "secretory system to", "system to the", "to the ciliary", "the ciliary base", "ciliary base and", "base and subsequently", "and subsequently transported", "subsequently transported to", "transported to the", "the ciliary tip", "tip where", "where extension of", "of the axoneme", "the axoneme occurs", "occurs by", "by a motor", "a motor driven", "motor driven process", "driven process called", "process called intraflagellar", "called intraflagellar transport", "transport ift", "ift . anterograde", ". anterograde transport", "anterograde transport of", "transport of cargo", "of cargo from", "cargo from the", "from the ciliary", "ciliary base to", "base to the", "to the tip", "the tip of", "tip of the", "the cilium requires", "cilium requires kinesin", "requires kinesin 2", "kinesin 2 type", "2 type motors", "motors while", "while the dynein", "the dynein 2", "dynein 2 motor", "2 motor is", "motor is required", "required for retrograde", "for retrograde transport", "retrograde transport back", "transport back to", "back to the", "the ciliary base.", "base. in", "addition both", "both anterograde and", "anterograde and retrograde", "and retrograde transport", "retrograde transport depend", "transport depend on", "depend on the", "on the ift", "the ift complex", "complex a", "a multiprotein assembly", "multiprotein assembly consisting", "assembly consisting of", "consisting of two", "of two subcomplexes", "subcomplexes ift", "ift a and", "a and ift", "and ift b.", "ift b. the", "b. the primary", "is a dynamic", "a dynamic structure", "dynamic structure that", "structure that undergoes", "that undergoes continuous", "undergoes continuous steady", "continuous steady state", "steady state turnover", "state turnover of", "turnover of tubulin", "of tubulin at", "tubulin at the", "at the tip", "tip as", "as a consequence", "consequence the", "the ift machinery", "ift machinery is", "machinery is required", "required for cilium", "for cilium maintenance", "cilium maintenance as", "maintenance as well", "well as biogenesis", "biogenesis reviewed", "reviewed in bhogaraju", "in bhogaraju et", "bhogaraju et al", "al 2013", "2013 hsiao", "2012 li", "li et al", "2012 taschner", "taschner et al", "2012 sung", "sung and leroux", "leroux 2013", "2013 . the", ". the importance", "the importance of", "importance of the", "the cilium in", "cilium in signaling", "in signaling and", "signaling and cell", "and cell biology", "cell biology is", "biology is highlighted", "is highlighted by", "highlighted by the", "by the wide", "the wide range", "wide range of", "range of defects", "of defects and", "defects and disorders", "disorders collectively", "collectively known as", "known as ciliopathies", "ciliopathies that", "that arise as", "arise as the", "as the result", "the result of", "result of mutations", "of mutations in", "mutations in genes", "in genes encoding", "genes encoding components", "encoding components of", "components of the", "of the ciliary", "the ciliary machinery", "machinery reviewed", "2010 madhivanan", "madhivanan and aguilar", "aguilar 2014", "cilia are membrane covered", "are membrane covered organelles", "membrane covered organelles that", "covered organelles that extend", "organelles that extend from", "that extend from the", "extend from the surface", "from the surface of", "the surface of eukaryotic", "surface of eukaryotic cells.", "of eukaryotic cells. cilia", "eukaryotic cells. cilia may", "cells. cilia may be", "cilia may be motile", "be motile such", "motile such as", "such as respiratory cilia", "respiratory cilia or", "cilia or non", "non motile such", "such as the primary", "as the primary cilium", "cilium and are", "and are distinguished by", "are distinguished by the", "distinguished by the structure", "by the structure of", "the structure of their", "structure of their microtubule", "of their microtubule based", "their microtubule based axonemes.", "microtubule based axonemes. the", "based axonemes. the axoneme", "axonemes. the axoneme consists", "the axoneme consists of", "axoneme consists of nine", "consists of nine peripheral", "of nine peripheral doublet", "nine peripheral doublet microtubules", "doublet microtubules and", "microtubules and in", "and in the case", "in the case of", "the case of many", "case of many motile", "of many motile cilia", "motile cilia may", "cilia may also", "may also contain a", "also contain a pair", "contain a pair of", "a pair of central", "pair of central single", "of central single microtubules.", "central single microtubules. these", "single microtubules. these are", "microtubules. these are referred", "these are referred to", "are referred to as", "referred to as 9+0", "to as 9+0 or", "as 9+0 or 9+2", "9+0 or 9+2 axonemes", "9+2 axonemes respectively.", "axonemes respectively. relative", "respectively. relative to their", "relative to their non", "to their non motile", "their non motile counterparts", "motile counterparts motile", "counterparts motile cilia", "motile cilia also contain", "cilia also contain additional", "also contain additional structures", "contain additional structures that", "additional structures that contribute", "structures that contribute to", "that contribute to motion", "to motion including", "motion including inner", "including inner and outer", "inner and outer dynein", "and outer dynein arms", "dynein arms radial", "arms radial spokes", "radial spokes and nexin", "spokes and nexin links.", "and nexin links. four", "nexin links. four main", "links. four main types", "four main types of", "main types of cilia", "types of cilia have", "of cilia have been", "cilia have been identified", "have been identified in", "been identified in humans:", "identified in humans: 9+2", "in humans: 9+2 motile", "9+2 motile such", "cilia 9+0", "9+0 motile nodal", "motile nodal cilia", "cilia 9+2", "non motile kinocilium", "motile kinocilium of", "kinocilium of hair cells", "hair cells and", "cells and 9+0", "and 9+0 non motile", "non motile primary", "motile primary cilium", "primary cilium and photoreceptor", "cilium and photoreceptor cells", "reviewed in fliegauf et", "in fliegauf et al", "et al 2007", "al 2007 .", "2007 . this pathway", ". this pathway describes", "this pathway describes cilia", "pathway describes cilia formation", "cilia formation with", "formation with an", "with an emphasis on", "an emphasis on the", "emphasis on the primary", "on the primary cilium.", "the primary cilium. the", "primary cilium. the primary", "cilium. the primary cilium", "the primary cilium is", "primary cilium is a", "cilium is a sensory", "is a sensory organelle", "a sensory organelle that", "sensory organelle that is", "organelle that is required", "that is required for", "is required for the", "required for the transduction", "for the transduction of", "the transduction of numerous", "transduction of numerous external", "of numerous external signals", "numerous external signals such", "external signals such as", "signals such as growth", "such as growth factors", "growth factors hormones", "factors hormones and", "and morphogens and", "morphogens and an", "and an intact primary", "an intact primary cilium", "intact primary cilium is", "primary cilium is needed", "cilium is needed for", "is needed for signaling", "needed for signaling pathways", "for signaling pathways mediated", "signaling pathways mediated by", "pathways mediated by hh", "by hh wnt", "calcium g protein", "g protein coupled receptors", "protein coupled receptors and", "coupled receptors and receptor", "receptors and receptor tyrosine", "and receptor tyrosine kinases", "tyrosine kinases among", "kinases among others", "among others reviewed", "others reviewed in", "reviewed in goetz and", "in goetz and anderson", "and anderson 2010", "2010 berbari et", "et al 2009", "nachury 2014 .", "2014 . unlike the", ". unlike the motile", "unlike the motile cilia", "motile cilia which", "cilia which are", "which are generally present", "are generally present in", "generally present in large", "present in large numbers", "in large numbers on", "large numbers on epithelial", "numbers on epithelial cells", "on epithelial cells and", "epithelial cells and are", "cells and are responsible", "and are responsible for", "are responsible for sensory", "responsible for sensory function", "for sensory function as", "sensory function as well", "function as well as", "as well as wave", "well as wave like", "as wave like beating", "wave like beating motions", "beating motions the", "motions the primary", "cilium is a non", "is a non motile", "a non motile sensory", "non motile sensory organelle", "motile sensory organelle that", "organelle that is present", "that is present in", "is present in a", "present in a single", "in a single copy", "a single copy at", "single copy at the", "copy at the apical", "at the apical surface", "the apical surface of", "apical surface of most", "surface of most quiescent", "of most quiescent cells", "quiescent cells reviewed", "cells reviewed in", "reviewed in hsiao et", "in hsiao et al", "et al 2012", "al 2012 .", "2012 . cilium biogenesis", ". cilium biogenesis involves", "cilium biogenesis involves the", "biogenesis involves the anchoring", "involves the anchoring of", "the anchoring of the", "anchoring of the basal", "of the basal body", "basal body a", "body a centriole", "a centriole derived organelle", "derived organelle near", "organelle near the", "near the plasma membrane", "the plasma membrane and", "plasma membrane and the", "membrane and the subsequent", "and the subsequent polymerization", "the subsequent polymerization of", "subsequent polymerization of the", "polymerization of the microtubule", "of the microtubule based", "the microtubule based axoneme", "microtubule based axoneme and", "based axoneme and extension", "axoneme and extension of", "and extension of the", "extension of the plasma", "of the plasma membrane", "plasma membrane reviewed", "membrane reviewed in", "reviewed in ishikawa and", "in ishikawa and marshall", "and marshall 2011", "2011 reiter et", "2012 . although the", ". although the ciliary", "although the ciliary membrane", "the ciliary membrane is", "ciliary membrane is continuous", "membrane is continuous with", "is continuous with the", "continuous with the plasma", "with the plasma membrane", "plasma membrane the", "membrane the protein", "the protein and lipid", "protein and lipid content", "and lipid content of", "lipid content of the", "content of the cilium", "of the cilium and", "the cilium and the", "cilium and the ciliary", "and the ciliary membrane", "the ciliary membrane are", "ciliary membrane are distinct", "membrane are distinct from", "are distinct from those", "distinct from those of", "from those of the", "those of the bulk", "of the bulk cytoplasm", "the bulk cytoplasm and", "bulk cytoplasm and plasma", "cytoplasm and plasma membrane", "reviewed in emmer et", "in emmer et al", "et al 2010", "2010 rohatgi and", "and snell 2010", "snell 2010 .", "2010 . this specialized", ". this specialized compartment", "this specialized compartment is", "specialized compartment is established", "compartment is established and", "is established and maintained", "established and maintained during", "and maintained during cilium", "maintained during cilium biogenesis", "during cilium biogenesis by", "cilium biogenesis by the", "biogenesis by the formation", "by the formation of", "the formation of a", "formation of a ciliary", "of a ciliary transition", "a ciliary transition zone", "transition zone a", "zone a proteinaceous", "a proteinaceous structure that", "structure that with", "that with the", "with the transition fibres", "transition fibres anchors", "fibres anchors the", "anchors the basal body", "the basal body to", "basal body to the", "body to the plasma", "to the plasma membrane", "plasma membrane and acts", "membrane and acts as", "and acts as a", "acts as a ciliary", "as a ciliary pore", "a ciliary pore to", "ciliary pore to limit", "pore to limit free", "to limit free diffusion", "limit free diffusion from", "free diffusion from the", "diffusion from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the cilium", "the cilium reviewed", "cilium reviewed in", "reviewed in nachury et", "in nachury et al", "2010 reiter et", "2012 . ciliary components", ". ciliary components are", "ciliary components are targeted", "components are targeted from", "are targeted from the", "targeted from the secretory", "from the secretory system", "the secretory system to", "secretory system to the", "system to the ciliary", "to the ciliary base", "the ciliary base and", "ciliary base and subsequently", "base and subsequently transported", "and subsequently transported to", "subsequently transported to the", "transported to the ciliary", "to the ciliary tip", "ciliary tip where", "tip where extension", "where extension of the", "extension of the axoneme", "of the axoneme occurs", "axoneme occurs by", "occurs by a", "by a motor driven", "a motor driven process", "motor driven process called", "driven process called intraflagellar", "process called intraflagellar transport", "intraflagellar transport ift", "transport ift .", "ift . anterograde transport", ". anterograde transport of", "anterograde transport of cargo", "transport of cargo from", "of cargo from the", "cargo from the ciliary", "from the ciliary base", "the ciliary base to", "ciliary base to the", "base to the tip", "to the tip of", "the tip of the", "tip of the cilium", "of the cilium requires", "the cilium requires kinesin", "cilium requires kinesin 2", "requires kinesin 2 type", "kinesin 2 type motors", "type motors while", "motors while the", "while the dynein 2", "the dynein 2 motor", "dynein 2 motor is", "2 motor is required", "motor is required for", "is required for retrograde", "required for retrograde transport", "for retrograde transport back", "retrograde transport back to", "transport back to the", "back to the ciliary", "to the ciliary base.", "ciliary base. in", "base. in addition", "in addition both", "addition both anterograde", "both anterograde and retrograde", "anterograde and retrograde transport", "and retrograde transport depend", "retrograde transport depend on", "transport depend on the", "depend on the ift", "on the ift complex", "ift complex a", "complex a multiprotein", "a multiprotein assembly consisting", "multiprotein assembly consisting of", "assembly consisting of two", "consisting of two subcomplexes", "two subcomplexes ift", "subcomplexes ift a", "ift a and ift", "a and ift b.", "and ift b. the", "ift b. the primary", "b. the primary cilium", "cilium is a dynamic", "is a dynamic structure", "a dynamic structure that", "dynamic structure that undergoes", "structure that undergoes continuous", "that undergoes continuous steady", "undergoes continuous steady state", "continuous steady state turnover", "steady state turnover of", "state turnover of tubulin", "turnover of tubulin at", "of tubulin at the", "tubulin at the tip", "the tip as", "tip as a", "a consequence the", "consequence the ift", "the ift machinery is", "ift machinery is required", "machinery is required for", "is required for cilium", "required for cilium maintenance", "for cilium maintenance as", "cilium maintenance as well", "maintenance as well as", "as well as biogenesis", "as biogenesis reviewed", "biogenesis reviewed in", "reviewed in bhogaraju et", "in bhogaraju et al", "et al 2013", "2013 hsiao et", "2012 li et", "2012 taschner et", "2012 sung and", "and leroux 2013", "leroux 2013 .", "2013 . the importance", ". the importance of", "the importance of the", "importance of the cilium", "of the cilium in", "the cilium in signaling", "cilium in signaling and", "in signaling and cell", "signaling and cell biology", "and cell biology is", "cell biology is highlighted", "biology is highlighted by", "is highlighted by the", "highlighted by the wide", "by the wide range", "the wide range of", "wide range of defects", "range of defects and", "of defects and disorders", "and disorders collectively", "disorders collectively known", "collectively known as ciliopathies", "as ciliopathies that", "ciliopathies that arise", "that arise as the", "arise as the result", "as the result of", "the result of mutations", "result of mutations in", "of mutations in genes", "mutations in genes encoding", "in genes encoding components", "genes encoding components of", "encoding components of the", "components of the ciliary", "of the ciliary machinery", "ciliary machinery reviewed", "machinery reviewed in", "2010 madhivanan and", "and aguilar 2014", "aguilar 2014 .", "cilia are membrane covered organelles", "are membrane covered organelles that", "membrane covered organelles that extend", "covered organelles that extend from", "organelles that extend from the", "that extend from the surface", "extend from the surface of", "from the surface of eukaryotic", "the surface of eukaryotic cells.", "surface of eukaryotic cells. cilia", "of eukaryotic cells. cilia may", "eukaryotic cells. cilia may be", "cells. cilia may be motile", "may be motile such", "be motile such as", "motile such as respiratory", "as respiratory cilia or", "respiratory cilia or non", "cilia or non motile", "or non motile such", "non motile such as", "motile such as the", "such as the primary cilium", "the primary cilium and", "primary cilium and are", "cilium and are distinguished", "and are distinguished by the", "are distinguished by the structure", "distinguished by the structure of", "by the structure of their", "the structure of their microtubule", "structure of their microtubule based", "of their microtubule based axonemes.", "their microtubule based axonemes. the", "microtubule based axonemes. the axoneme", "based axonemes. the axoneme consists", "axonemes. the axoneme consists of", "the axoneme consists of nine", "axoneme consists of nine peripheral", "consists of nine peripheral doublet", "of nine peripheral doublet microtubules", "peripheral doublet microtubules and", "doublet microtubules and in", "microtubules and in the", "and in the case of", "in the case of many", "the case of many motile", "case of many motile cilia", "many motile cilia may", "motile cilia may also", "cilia may also contain", "may also contain a pair", "also contain a pair of", "contain a pair of central", "a pair of central single", "pair of central single microtubules.", "of central single microtubules. these", "central single microtubules. these are", "single microtubules. these are referred", "microtubules. these are referred to", "these are referred to as", "are referred to as 9+0", "referred to as 9+0 or", "to as 9+0 or 9+2", "as 9+0 or 9+2 axonemes", "or 9+2 axonemes respectively.", "9+2 axonemes respectively. relative", "axonemes respectively. relative to", "respectively. relative to their non", "relative to their non motile", "to their non motile counterparts", "non motile counterparts motile", "motile counterparts motile cilia", "counterparts motile cilia also", "motile cilia also contain additional", "cilia also contain additional structures", "also contain additional structures that", "contain additional structures that contribute", "additional structures that contribute to", "structures that contribute to motion", "contribute to motion including", "to motion including inner", "motion including inner and", "including inner and outer dynein", "inner and outer dynein arms", "outer dynein arms radial", "dynein arms radial spokes", "arms radial spokes and", "radial spokes and nexin links.", "spokes and nexin links. four", "and nexin links. four main", "nexin links. four main types", "links. four main types of", "four main types of cilia", "main types of cilia have", "types of cilia have been", "of cilia have been identified", "cilia have been identified in", "have been identified in humans:", "been identified in humans: 9+2", "identified in humans: 9+2 motile", "humans: 9+2 motile such", "9+2 motile such as", "respiratory cilia 9+0", "cilia 9+0 motile", "9+0 motile nodal cilia", "nodal cilia 9+2", "cilia 9+2 non", "9+2 non motile kinocilium", "non motile kinocilium of", "motile kinocilium of hair", "of hair cells and", "hair cells and 9+0", "cells and 9+0 non", "9+0 non motile primary", "non motile primary cilium", "motile primary cilium and", "primary cilium and photoreceptor cells", "reviewed in fliegauf et al", "fliegauf et al 2007", "et al 2007 .", "al 2007 . this", "2007 . this pathway describes", ". this pathway describes cilia", "this pathway describes cilia formation", "describes cilia formation with", "cilia formation with an", "formation with an emphasis", "with an emphasis on the", "an emphasis on the primary", "emphasis on the primary cilium.", "on the primary cilium. the", "the primary cilium. the primary", "primary cilium. the primary cilium", "cilium. the primary cilium is", "the primary cilium is a", "primary cilium is a sensory", "cilium is a sensory organelle", "is a sensory organelle that", "a sensory organelle that is", "sensory organelle that is required", "organelle that is required for", "that is required for the", "is required for the transduction", "required for the transduction of", "for the transduction of numerous", "the transduction of numerous external", "transduction of numerous external signals", "of numerous external signals such", "numerous external signals such as", "external signals such as growth", "signals such as growth factors", "as growth factors hormones", "growth factors hormones and", "factors hormones and morphogens", "hormones and morphogens and", "and morphogens and an", "morphogens and an intact", "and an intact primary cilium", "an intact primary cilium is", "intact primary cilium is needed", "primary cilium is needed for", "cilium is needed for signaling", "is needed for signaling pathways", "needed for signaling pathways mediated", "for signaling pathways mediated by", "signaling pathways mediated by hh", "mediated by hh wnt", "hh wnt calcium", "wnt calcium g", "calcium g protein coupled", "g protein coupled receptors and", "protein coupled receptors and receptor", "coupled receptors and receptor tyrosine", "receptors and receptor tyrosine kinases", "receptor tyrosine kinases among", "tyrosine kinases among others", "among others reviewed in", "others reviewed in goetz", "reviewed in goetz and anderson", "goetz and anderson 2010", "anderson 2010 berbari", "2010 berbari et al", "berbari et al 2009", "al 2009 nachury", "2009 nachury 2014", "nachury 2014 . unlike", "2014 . unlike the motile", ". unlike the motile cilia", "the motile cilia which", "motile cilia which are", "cilia which are generally", "which are generally present in", "are generally present in large", "generally present in large numbers", "present in large numbers on", "in large numbers on epithelial", "large numbers on epithelial cells", "numbers on epithelial cells and", "on epithelial cells and are", "epithelial cells and are responsible", "cells and are responsible for", "and are responsible for sensory", "are responsible for sensory function", "responsible for sensory function as", "for sensory function as well", "sensory function as well as", "function as well as wave", "as well as wave like", "well as wave like beating", "as wave like beating motions", "like beating motions the", "beating motions the primary", "motions the primary cilium", "primary cilium is a non", "cilium is a non motile", "is a non motile sensory", "a non motile sensory organelle", "non motile sensory organelle that", "motile sensory organelle that is", "sensory organelle that is present", "organelle that is present in", "that is present in a", "is present in a single", "present in a single copy", "in a single copy at", "a single copy at the", "single copy at the apical", "copy at the apical surface", "at the apical surface of", "the apical surface of most", "apical surface of most quiescent", "surface of most quiescent cells", "most quiescent cells reviewed", "quiescent cells reviewed in", "cells reviewed in hsiao", "reviewed in hsiao et al", "hsiao et al 2012", "et al 2012 .", "al 2012 . cilium", "2012 . cilium biogenesis involves", ". cilium biogenesis involves the", "cilium biogenesis involves the anchoring", "biogenesis involves the anchoring of", "involves the anchoring of the", "the anchoring of the basal", "anchoring of the basal body", "the basal body a", "basal body a centriole", "body a centriole derived", "centriole derived organelle near", "derived organelle near the", "organelle near the plasma", "near the plasma membrane and", "the plasma membrane and the", "plasma membrane and the subsequent", "membrane and the subsequent polymerization", "and the subsequent polymerization of", "the subsequent polymerization of the", "subsequent polymerization of the microtubule", "polymerization of the microtubule based", "of the microtubule based axoneme", "the microtubule based axoneme and", "microtubule based axoneme and extension", "based axoneme and extension of", "axoneme and extension of the", "and extension of the plasma", "extension of the plasma membrane", "the plasma membrane reviewed", "plasma membrane reviewed in", "membrane reviewed in ishikawa", "reviewed in ishikawa and marshall", "ishikawa and marshall 2011", "marshall 2011 reiter", "2011 reiter et al", "reiter et al 2012", "al 2012 . although", "2012 . although the ciliary", ". although the ciliary membrane", "although the ciliary membrane is", "the ciliary membrane is continuous", "ciliary membrane is continuous with", "membrane is continuous with the", "is continuous with the plasma", "continuous with the plasma membrane", "the plasma membrane the", "plasma membrane the protein", "membrane the protein and", "the protein and lipid content", "protein and lipid content of", "and lipid content of the", "lipid content of the cilium", "content of the cilium and", "of the cilium and the", "the cilium and the ciliary", "cilium and the ciliary membrane", "and the ciliary membrane are", "the ciliary membrane are distinct", "ciliary membrane are distinct from", "membrane are distinct from those", "are distinct from those of", "distinct from those of the", "from those of the bulk", "those of the bulk cytoplasm", "of the bulk cytoplasm and", "the bulk cytoplasm and plasma", "bulk cytoplasm and plasma membrane", "and plasma membrane reviewed", "membrane reviewed in emmer", "reviewed in emmer et al", "emmer et al 2010", "al 2010 rohatgi", "2010 rohatgi and snell", "rohatgi and snell 2010", "and snell 2010 .", "snell 2010 . this", "2010 . this specialized compartment", ". this specialized compartment is", "this specialized compartment is established", "specialized compartment is established and", "compartment is established and maintained", "is established and maintained during", "established and maintained during cilium", "and maintained during cilium biogenesis", "maintained during cilium biogenesis by", "during cilium biogenesis by the", "cilium biogenesis by the formation", "biogenesis by the formation of", "by the formation of a", "the formation of a ciliary", "formation of a ciliary transition", "of a ciliary transition zone", "ciliary transition zone a", "transition zone a proteinaceous", "zone a proteinaceous structure", "proteinaceous structure that with", "structure that with the", "that with the transition", "the transition fibres anchors", "transition fibres anchors the", "fibres anchors the 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"acids like", "like arachidonic", "arachidonic acid", "acid and", "and phospholipids", "phospholipids in", "in vitro", "but the", "the in", "in vivo", "vivo significance", "significance of", "of this", "this activation", "activation remains", "remains unclear", "palmer et", "al. 1995", "yoshinaga et", "1999 .

pkns", ".

pkns play", "play important", "important roles", "roles in", "in diverse", "diverse functions", "including regulation", "regulation of", "of cell", "cell cycle", "receptor trafficking", "vesicle transport", "transport and", "and apoptosis.", "apoptosis. pkn", "pkn is", "is also", "also involved", "the ligand", "ligand dependent", "dependent transcriptional", "transcriptional activation", "activation by", "by the", "the androgen", "androgen receptor.", "receptor. more", "more than", "than 20", "20 proteins", "proteins and", "and several", "several peptides", "peptides have", "have been", "been shown", "shown to", "to be", "be phosphorylated", "phosphorylated by", "by pkn1", "pkn1 and", "and pkn2", "including cpi", "cpi 17", "hamaguchi et", "alpha actinin", "mukai et", "al. 1997", "collazos et", "misaki et", "al. 2001", "matsuzawa et", "kato et", "and egfr", "2011 .", ". there", "there are", "are no", "no known", "known substrates", "substrates for", "for pkn3", "protein kinases n", "n pkn", "also known as", "known as protein", "as protein kinase", "protein kinase c", "kinase c related", "c related kinases", "kinases pkr", "pkr feature", "feature a c", "a c terminal", "c terminal serine/threonine", "terminal serine/threonine kinase", "serine/threonine kinase domain", "kinase domain and", "domain and three", "and three rho", "three rho binding", "rho binding motifs", "binding motifs at", "motifs at the", "at the n", "the n terminus.", "n terminus. rho", "terminus. rho gtpases", "rho gtpases rhoa", "rhoa rhob", "rhob rhoc", "rhoc and rac1", "and rac1 bind", "rac1 bind pkn1", "pkn1 pkn2", "pkn2 and pkn3", "pkn3 maesaki", "maesaki et al.", "et al. 1999", "1999 zhong", "zhong et al.", "1999 owen", "owen et al.", "et al. 2003", "2003 modha", "modha et al.", "et al. 2008", "2008 hutchinson", "hutchinson et al.", "et al. 2011", "2011 hutchinson", "et al. 2013", "bringing them in", "them in proximity", "in proximity to", "proximity to the", "to the pip3", "the pip3 activated", "pip3 activated co", "activated co activator", "co activator pdpk1", "pdpk1 pdk1", "flynn et al.", "et al. 2000", "2000 torbett", "torbett et al.", "al. 2003 .", "2003 . pdpk1", ". pdpk1 phosphorylates", "pdpk1 phosphorylates pkns", "phosphorylates pkns on", "pkns on a", "on a highly", "a highly conserved", "highly conserved threonine", "conserved threonine residue", "threonine residue in", "residue in the", "in the kinase", "the kinase activation", "kinase activation loop", "loop which", "which is a", "is a prerequisite", "a prerequisite for", "prerequisite for pkn", "for pkn activation.", "pkn activation. phosphorylation", "activation. phosphorylation of", "phosphorylation of other", "of other residues", "other residues might", "residues might also", "might also be", "also be involved", "be involved in", "involved in activation", "activation flynn", "2003 dettori", "dettori et al.", "et al. 2009", "al. 2009 .", "2009 . pkns", ". pkns are", "pkns are activated", "are activated by", "activated by fatty", "by fatty acids", "fatty acids like", "acids like arachidonic", "like arachidonic acid", "arachidonic acid and", "acid and phospholipids", "and phospholipids in", "phospholipids in vitro", "vitro but", "but the in", "the in vivo", "in vivo significance", "vivo significance of", "significance of this", "of this activation", "this activation remains", "activation remains unclear", "unclear palmer", "palmer et al.", "et al. 1995", "1995 yoshinaga", "yoshinaga et al.", "al. 1999 .

pkns", "1999 .

pkns play", ".

pkns play important", "play important roles", "important roles in", "roles in diverse", "in diverse functions", "functions including", "including regulation of", "regulation of cell", "of cell cycle", "cycle receptor", "trafficking vesicle", "vesicle transport and", "transport and apoptosis.", "and apoptosis. pkn", "apoptosis. pkn is", "pkn is also", "is also involved", "also involved in", "involved in the", "in the ligand", "the ligand dependent", "ligand dependent transcriptional", "dependent transcriptional activation", "transcriptional activation by", "activation by the", "by the androgen", "the androgen receptor.", "androgen receptor. more", "receptor. more than", "more than 20", "than 20 proteins", "20 proteins and", "proteins and several", "and several peptides", "several peptides have", "peptides have been", "have been shown", "been shown to", "shown to be", "to be phosphorylated", "be phosphorylated by", "phosphorylated by pkn1", "by pkn1 and", "pkn1 and pkn2", "pkn2 including", "including cpi 17", "17 hamaguchi", "hamaguchi et al.", "actinin mukai", "mukai et al.", "et al. 1997", "adducin collazos", "collazos et al.", "cdc25c misaki", "misaki et al.", "et al. 2001", "vimentin matsuzawa", "matsuzawa et al.", "traf1 kato", "kato et al.", "clip170 collazos", "2011 and", "egfr collazos", "al. 2011 .", "2011 . there", ". there are", "there are no", "are no known", "no known substrates", "known substrates for", "substrates for pkn3", "pkn3 collazos", "kinases n pkn", "pkn also", "also known as protein", "known as protein kinase", "as protein kinase c", "protein kinase c related", "kinase c related kinases", "related kinases pkr", "pkr feature a", "feature a c terminal", "a c terminal serine/threonine", "c terminal serine/threonine kinase", "terminal serine/threonine kinase domain", "serine/threonine kinase domain and", "kinase domain and three", "domain and three rho", "and three rho binding", "three rho binding motifs", "rho binding motifs at", "binding motifs at the", "motifs at the n", "at the n terminus.", "the n terminus. rho", "n terminus. rho gtpases", "terminus. rho gtpases rhoa", "gtpases rhoa rhob", "rhob rhoc and", "rhoc and rac1 bind", "and rac1 bind pkn1", "bind pkn1 pkn2", "pkn1 pkn2 and", "and pkn3 maesaki", "pkn3 maesaki et", "maesaki et al. 1999", "al. 1999 zhong", "1999 zhong et", "zhong et al. 1999", "al. 1999 owen", "1999 owen et", "owen et al. 2003", "al. 2003 modha", "2003 modha et", "modha et al. 2008", "al. 2008 hutchinson", "2008 hutchinson et", "hutchinson et al. 2011", "al. 2011 hutchinson", "2011 hutchinson et", "hutchinson et al. 2013", "2013 bringing", "bringing them in proximity", "them in proximity to", "in proximity to the", "proximity to the pip3", "to the pip3 activated", "the pip3 activated co", "pip3 activated co activator", "activated co activator pdpk1", "activator pdpk1 pdk1", "pdk1 flynn", "flynn et al. 2000", "al. 2000 torbett", "2000 torbett et", "torbett et al. 2003", "et al. 2003 .", "al. 2003 . pdpk1", "2003 . pdpk1 phosphorylates", ". pdpk1 phosphorylates pkns", "pdpk1 phosphorylates pkns on", "phosphorylates pkns on a", "pkns on a highly", "on a highly conserved", "a highly conserved threonine", "highly conserved threonine residue", "conserved threonine residue in", "threonine residue in the", "residue in the kinase", "in the kinase activation", "the kinase activation loop", "activation loop which", "loop which is", "which is a prerequisite", "is a prerequisite for", "a prerequisite for pkn", "prerequisite for pkn activation.", "for pkn activation. phosphorylation", "pkn activation. phosphorylation of", "activation. phosphorylation of other", "phosphorylation of other residues", "of other residues might", "other residues might also", "residues might also be", "might also be involved", "also be involved in", "be involved in activation", "in activation flynn", "activation flynn et", "al. 2003 dettori", "2003 dettori et", "dettori et al. 2009", "et al. 2009 .", "al. 2009 . pkns", "2009 . pkns are", ". pkns are activated", "pkns are activated by", "are activated by fatty", "activated by fatty acids", "by fatty acids like", "fatty acids like arachidonic", "acids like arachidonic acid", "like arachidonic acid and", "arachidonic acid and phospholipids", "acid and phospholipids in", "and phospholipids in vitro", "in vitro but", "vitro but the", "but the in vivo", "the in vivo significance", "in vivo significance of", "vivo significance of this", "significance of this activation", "of this activation remains", "this activation remains unclear", "remains unclear palmer", "unclear palmer et", "palmer et al. 1995", "al. 1995 yoshinaga", "1995 yoshinaga et", "yoshinaga et al. 1999", "et al. 1999 .

pkns", "al. 1999 .

pkns play", "1999 .

pkns play important", ".

pkns play important roles", "play important roles in", "important roles in diverse", "roles in diverse functions", "diverse functions including", "functions including regulation", "including regulation of cell", "regulation of cell cycle", "cell cycle receptor", "cycle receptor trafficking", "receptor trafficking vesicle", "trafficking vesicle transport", "vesicle transport and apoptosis.", "transport and apoptosis. pkn", "and apoptosis. pkn is", "apoptosis. pkn is also", "pkn is also involved", "is also involved in", "also involved in the", "involved in the ligand", "in the ligand dependent", "the ligand dependent transcriptional", "ligand dependent transcriptional activation", "dependent transcriptional activation by", "transcriptional activation by the", "activation by the androgen", "by the androgen receptor.", "the androgen receptor. more", "androgen receptor. more than", "receptor. more than 20", "more than 20 proteins", "than 20 proteins and", "20 proteins and several", "proteins and several peptides", "and several peptides have", "several peptides have been", "peptides have been shown", "have been shown to", "been shown to be", "shown to be phosphorylated", "to be phosphorylated by", "be phosphorylated by pkn1", "phosphorylated by pkn1 and", "by pkn1 and pkn2", "and pkn2 including", "pkn2 including cpi", "cpi 17 hamaguchi", "17 hamaguchi et", "hamaguchi et al. 2000", "2000 alpha", "alpha actinin mukai", "actinin mukai et", "mukai et al. 1997", "1997 adducin", "adducin collazos et", "collazos et al. 2011", "2011 cdc25c", "cdc25c misaki et", "misaki et al. 2001", "2001 vimentin", "vimentin matsuzawa et", "matsuzawa et al. 1997", "1997 traf1", "traf1 kato et", "kato et al. 2008", "2008 clip170", "clip170 collazos et", "al. 2011 and", "2011 and egfr", "and egfr collazos", "egfr collazos et", "et al. 2011 .", "al. 2011 . there", "2011 . there are", ". there are no", "there are no known", "are no known substrates", "no known substrates for", "known substrates for pkn3", "for pkn3 collazos", "pkn3 collazos et", "protein kinases n pkn", "pkn also known", "also known as protein kinase", "known as protein kinase c", "as protein kinase c related", "protein kinase c related kinases", "c related kinases pkr", "kinases pkr feature", "pkr feature a c", "feature a c terminal serine/threonine", "a c terminal serine/threonine kinase", "c terminal serine/threonine kinase domain", "terminal serine/threonine kinase domain and", "serine/threonine kinase domain and three", "kinase domain and three rho", "domain and three rho binding", "and three rho binding motifs", "three rho binding motifs at", "rho binding motifs at the", "binding motifs at the n", "motifs at the n terminus.", "at the n terminus. rho", "the n terminus. rho gtpases", "n terminus. rho gtpases rhoa", "rho gtpases rhoa rhob", "rhoa rhob rhoc", "rhob rhoc and rac1", "rhoc and rac1 bind pkn1", "rac1 bind pkn1 pkn2", "bind pkn1 pkn2 and", "pkn1 pkn2 and pkn3", "pkn2 and pkn3 maesaki", "and pkn3 maesaki et", "pkn3 maesaki et al.", "et al. 1999 zhong", "al. 1999 zhong et", "1999 zhong et al.", "et al. 1999 owen", "al. 1999 owen et", "1999 owen et al.", "et al. 2003 modha", "al. 2003 modha et", "2003 modha et al.", "et al. 2008 hutchinson", "al. 2008 hutchinson et", "2008 hutchinson et al.", "et al. 2011 hutchinson", "al. 2011 hutchinson et", "2011 hutchinson et al.", "al. 2013 bringing", "2013 bringing them", "bringing them in proximity to", "them in proximity to the", "in proximity to the pip3", "proximity to the pip3 activated", "to the pip3 activated co", "the pip3 activated co activator", "pip3 activated co activator pdpk1", "co activator pdpk1 pdk1", "pdk1 flynn et", "et al. 2000 torbett", "al. 2000 torbett et", "2000 torbett et al.", "torbett et al. 2003 .", "et al. 2003 . pdpk1", "al. 2003 . pdpk1 phosphorylates", "2003 . pdpk1 phosphorylates pkns", ". pdpk1 phosphorylates pkns on", "pdpk1 phosphorylates pkns on a", "phosphorylates pkns on a highly", "pkns on a highly conserved", "on a highly conserved threonine", "a highly conserved threonine residue", "highly conserved threonine residue in", "conserved threonine residue in the", "threonine residue in the kinase", "residue in the kinase activation", "in the kinase activation loop", "kinase activation loop which", "activation loop which is", "loop which is a", "which is a prerequisite for", "is a prerequisite for pkn", "a prerequisite for pkn activation.", "prerequisite for pkn activation. phosphorylation", "for pkn activation. phosphorylation of", "pkn activation. phosphorylation of other", "activation. phosphorylation of other residues", "phosphorylation of other residues might", "of other residues might also", "other residues might also be", "residues might also be involved", "might also be involved in", "also be involved in activation", "involved in activation flynn", "in activation flynn et", "activation flynn et al.", "et al. 2003 dettori", "al. 2003 dettori et", "2003 dettori et al.", "dettori et al. 2009 .", "et al. 2009 . pkns", "al. 2009 . pkns are", "2009 . pkns are activated", ". pkns are activated by", "pkns are activated by fatty", "are activated by fatty acids", "activated by fatty acids like", "by fatty acids like arachidonic", "fatty acids like arachidonic acid", "acids like arachidonic acid and", "like arachidonic acid and phospholipids", "arachidonic acid and phospholipids in", "acid and phospholipids in vitro", "phospholipids in vitro but", "in vitro but the", "vitro but the in", "but the in vivo significance", "the in vivo significance of", "in vivo significance of this", "vivo significance of this activation", "significance of this activation remains", "of this activation remains unclear", "activation remains unclear palmer", "remains unclear palmer et", "unclear palmer et al.", "et al. 1995 yoshinaga", "al. 1995 yoshinaga et", "1995 yoshinaga et al.", "yoshinaga et al. 1999 .

pkns", "et al. 1999 .

pkns play", "al. 1999 .

pkns play important", "1999 .

pkns play important roles", ".

pkns play important roles in", "play important roles in diverse", "important roles in diverse functions", "in diverse functions including", "diverse functions including regulation", "functions including regulation of", "including regulation of cell cycle", "of cell cycle receptor", "cell cycle receptor trafficking", "receptor trafficking vesicle transport", "trafficking vesicle transport and", "vesicle transport and apoptosis. pkn", "transport and apoptosis. pkn is", "and apoptosis. pkn is also", "apoptosis. pkn is also involved", "pkn is also involved in", "is also involved in the", "also involved in the ligand", "involved in the ligand dependent", "in the ligand dependent transcriptional", "the ligand dependent transcriptional activation", "ligand dependent transcriptional activation by", "dependent transcriptional activation by the", "transcriptional activation by the androgen", "activation by the androgen receptor.", "by the androgen receptor. more", "the androgen receptor. more than", "androgen receptor. more than 20", "receptor. more than 20 proteins", "more than 20 proteins and", "than 20 proteins and several", "20 proteins and several peptides", "proteins and several peptides have", "and several peptides have been", "several peptides have been shown", "peptides have been shown to", "have been shown to be", "been shown to be phosphorylated", "shown to be phosphorylated by", "to be phosphorylated by pkn1", "be phosphorylated by pkn1 and", "phosphorylated by pkn1 and pkn2", "pkn1 and pkn2 including", "and pkn2 including cpi", "pkn2 including cpi 17", "including cpi 17 hamaguchi", "cpi 17 hamaguchi et", "17 hamaguchi et al.", "al. 2000 alpha", "2000 alpha actinin", "alpha actinin mukai et", "actinin mukai et al.", "al. 1997 adducin", "adducin collazos et al.", "al. 2011 cdc25c", "cdc25c misaki et al.", "al. 2001 vimentin", "vimentin matsuzawa et al.", "al. 1997 traf1", "traf1 kato et al.", "al. 2008 clip170", "clip170 collazos et al.", "et al. 2011 and", "al. 2011 and egfr", "and egfr collazos et", "egfr collazos et al.", "collazos et al. 2011 .", "et al. 2011 . there", "al. 2011 . there are", "2011 . there are no", ". there are no known", "there are no known substrates", "are no known substrates for", "no known substrates for pkn3", "substrates for pkn3 collazos", "for pkn3 collazos et", "pkn3 collazos et al." ] }, { "record_id": "GLY_000594_1_464", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5625900", "r hsa", "hsa 5625900", "r hsa 5625900" ] }, { "record_id": "GLY_000594_1_464", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate cit", "rho gtpases activate", "gtpases activate cit", "rho gtpases activate cit", "citron kinase", "or citron", "citron rho", "rho interacting", "interacting kinase", "shares similarities", "similarities with", "with rock", "rock kinases.", "kinases. like", "like rock", "it consists", "consists of", "of a", "a serine/threonine", "serine/threonine kinase", "kinase domain", "a coiled", "coiled coil", "coil region", "a rho", "rho binding", "binding domain", "a cysteine", "cysteine rich", "rich region", "region and", "and a", "a plekstrin", "plekstrin homology", "but additionally", "additionally features", "features a", "a proline", "proline rich", "a pdz", "pdz binding", "binding domain.", "domain. a", "a shorter", "shorter splicing", "splicing isoform", "isoform of", "of cit", "citron n", "is specifically", "specifically expressed", "expressed in", "in the", "the nervous", "nervous system", "system and", "and lacks", "lacks the", "the kinase", "kinase domain.", "domain. citron", "n is", "is a", "a component", "component of", "of the", "the post", "post synaptic", "synaptic density", "where it", "it binds", "binds to", "to the", "the pdz", "pdz domains", "domains of", "the scaffolding", "scaffolding protein", "protein pds", "pds 95/sap90", "zhang et", "et al.", "al. 2006", "2006 .

while", ".

while the", "the binding", "binding of", "cit to", "to rho", "gtpases rhoa", "rhoc and", "and rac1", "rac1 is", "is well", "well established", "madaule et", "al. 1995", "the mechanism", "mechanism of", "cit activation", "activation by", "by gtp", "gtp bound", "bound rho", "gtpases has", "has not", "not been", "been elucidated.", "elucidated. there", "there are", "are indications", "indications that", "that cit", "cit may", "may be", "be activated", "activated through", "through autophosphorylation", "autophosphorylation in", "the presence", "presence of", "of active", "active forms", "forms of", "of rho", "di cunto", "cunto et", "al. 1998", "1998 .", ". cit", "cit appears", "appears to", "to phosphorylate", "phosphorylate the", "the myosin", "myosin regulatory", "regulatory light", "light chain", "the only", "only substrate", "substrate identified", "identified to", "to date", "on the", "the same", "same residues", "residues that", "that are", "are phosphorylated", "phosphorylated by", "by rocks", "but it", "it has", "been established", "established yet", "yet how", "how this", "this relates", "relates to", "to activation", "by rho", "yamashiro et", "al. 2003", "2003 .", "cit and", "and rhoa", "rhoa are", "are implicated", "implicated to", "to act", "act together", "together in", "in golgi", "golgi apparatus", "apparatus organization", "organization through", "through regulation", "regulation of", "the actin", "actin cytoskeleton", "camera et", "cit is", "is also", "also involved", "involved in", "the regulation", "of cytokinesis", "cytokinesis through", "through its", "its interaction", "interaction with", "with kif14", "gruneberg et", "bassi et", "al. 2013", "watanabe et", "and p27", "p27 kip1", "serres et", "al. 2012", "2012 .", "kinase cit", "cit or", "or citron rho", "citron rho interacting", "rho interacting kinase", "kinase crik", "crik shares", "shares similarities with", "similarities with rock", "with rock kinases.", "rock kinases. like", "kinases. like rock", "rock it", "it consists of", "consists of a", "of a serine/threonine", "a serine/threonine kinase", "serine/threonine kinase domain", "domain a", "a coiled coil", "coiled coil region", "region a", "a rho binding", "rho binding domain", "a cysteine rich", "cysteine rich region", "rich region and", "region and a", "and a plekstrin", "a plekstrin homology", "homology ph", "ph domain", "domain but", "but additionally features", "additionally features a", "features a proline", "a proline rich", "proline rich region", "and a pdz", "a pdz binding", "pdz binding domain.", "binding domain. a", "domain. a shorter", "a shorter splicing", "shorter splicing isoform", "splicing isoform of", "isoform of cit", "cit citron", "is specifically expressed", "specifically expressed in", "expressed in the", "in the nervous", "the nervous system", "nervous system and", "system and lacks", "and lacks the", "lacks the kinase", "the kinase domain.", "kinase domain. citron", "domain. citron n", "citron n is", "n is a", "is a component", "a component of", "component of the", "of the post", "the post synaptic", "post synaptic density", "density where", "where it binds", "it binds to", "binds to the", "to the pdz", "the pdz domains", "pdz domains of", "domains of the", "of the scaffolding", "the scaffolding protein", "scaffolding protein pds", "protein pds 95/sap90", "95/sap90 zhang", "zhang et al.", "et al. 2006", "al. 2006 .

while", "2006 .

while the", ".

while the binding", "the binding of", "binding of cit", "of cit to", "cit to rho", "to rho gtpases", "rho gtpases rhoa", "rhoa rhob", "rhob rhoc", "rhoc and rac1", "and rac1 is", "rac1 is well", "is well established", "established madaule", "madaule et al.", "et al. 1995", "the mechanism of", "mechanism of cit", "of cit activation", "cit activation by", "activation by gtp", "by gtp bound", "gtp bound rho", "bound rho gtpases", "rho gtpases has", "gtpases has not", "has not been", "not been elucidated.", "been elucidated. there", "elucidated. there are", "there are indications", "are indications that", "indications that cit", "that cit may", "cit may be", "may be activated", "be activated through", "activated through autophosphorylation", "through autophosphorylation in", "autophosphorylation in the", "in the presence", "the presence of", "presence of active", "of active forms", "active forms of", "forms of rho", "of rho gtpases", "gtpases di", "di cunto et", "cunto et al.", "et al. 1998", "al. 1998 .", "1998 . cit", ". cit appears", "cit appears to", "appears to phosphorylate", "to phosphorylate the", "phosphorylate the myosin", "the myosin regulatory", "myosin regulatory light", "regulatory light chain", "chain mrlc", "the only substrate", "only substrate identified", "substrate identified to", "identified to date", "date on", "on the same", "the same residues", "same residues that", "residues that are", "that are phosphorylated", "are phosphorylated by", "phosphorylated by rocks", "rocks but", "but it has", "it has not", "not been established", "been established yet", "established yet how", "yet how this", "how this relates", "this relates to", "relates to activation", "to activation by", "activation by rho", "by rho gtpases", "gtpases yamashiro", "yamashiro et al.", "et al. 2003", "al. 2003 .", "2003 . cit", ". cit and", "cit and rhoa", "and rhoa are", "rhoa are implicated", "are implicated to", "implicated to act", "to act together", "act together in", "together in golgi", "in golgi apparatus", "golgi apparatus organization", "apparatus organization through", "organization through regulation", "through regulation of", "regulation of the", "of the actin", "the actin cytoskeleton", "cytoskeleton camera", "camera et al.", ". cit is", "cit is also", "is also involved", "also involved in", "involved in the", "in the regulation", "the regulation of", "regulation of cytokinesis", "of cytokinesis through", "cytokinesis through its", "through its interaction", "its interaction with", "interaction with kif14", "kif14 gruneberg", "gruneberg et al.", "2006 bassi", "bassi et al.", "et al. 2013", "2013 watanabe", "watanabe et al.", "2013 and", "and p27 kip1", "serres et al.", "et al. 2012", "al. 2012 .", "citron kinase cit", "cit or citron", "or citron rho interacting", "citron rho interacting kinase", "interacting kinase crik", "crik shares similarities", "shares similarities with rock", "similarities with rock kinases.", "with rock kinases. like", "rock kinases. like rock", "like rock it", "rock it consists", "it consists of a", "consists of a serine/threonine", "of a serine/threonine kinase", "a serine/threonine kinase domain", "kinase domain a", "domain a coiled", "a coiled coil region", "coil region a", "region a rho", "a rho binding domain", "binding domain a", "domain a cysteine", "a cysteine rich region", "cysteine rich region and", "rich region and a", "region and a plekstrin", "and a plekstrin homology", "plekstrin homology ph", "domain but additionally", "but additionally features a", "additionally features a proline", "features a proline rich", "a proline rich region", "proline rich region and", "region and a pdz", "and a pdz binding", "a pdz binding domain.", "pdz binding domain. a", "binding domain. a shorter", "domain. a shorter splicing", "a shorter splicing isoform", "shorter splicing isoform of", "splicing isoform of cit", "of cit citron", "cit citron n", "n is specifically", "is specifically expressed in", "specifically expressed in the", "expressed in the nervous", "in the nervous system", "the nervous system and", "nervous system and lacks", "system and lacks the", "and lacks the kinase", "lacks the kinase domain.", "the kinase domain. citron", "kinase domain. citron n", "domain. citron n is", "citron n is a", "n is a component", "is a component of", "a component of the", "component of the post", "of the post synaptic", "the post synaptic density", "synaptic density where", "density where it", "where it binds to", "it binds to the", "binds to the pdz", "to the pdz domains", "the pdz domains of", "pdz domains of the", "domains of the scaffolding", "of the scaffolding protein", "the scaffolding protein pds", "scaffolding protein pds 95/sap90", "pds 95/sap90 zhang", "95/sap90 zhang et", "zhang et al. 2006", "et al. 2006 .

while", "al. 2006 .

while the", "2006 .

while the binding", ".

while the binding of", "the binding of cit", "binding of cit to", "of cit to rho", "cit to rho gtpases", "to rho gtpases rhoa", "gtpases rhoa rhob", "rhob rhoc and", "rhoc and rac1 is", "and rac1 is well", "rac1 is well established", "well established madaule", "established madaule et", "madaule et al. 1995", "1995 the", "the mechanism of cit", "mechanism of cit activation", "of cit activation by", "cit activation by gtp", "activation by gtp bound", "by gtp bound rho", "gtp bound rho gtpases", "bound rho gtpases has", "rho gtpases has not", "gtpases has not been", "has not been elucidated.", "not been elucidated. there", "been elucidated. there are", "elucidated. there are indications", "there are indications that", "are indications that cit", "indications that cit may", "that cit may be", "cit may be activated", "may be activated through", "be activated through autophosphorylation", "activated through autophosphorylation in", "through autophosphorylation in the", "autophosphorylation in the presence", "in the presence of", "the presence of active", "presence of active forms", "of active forms of", "active forms of rho", "forms of rho gtpases", "rho gtpases di", "gtpases di cunto", "di cunto et al.", "cunto et al. 1998", "et al. 1998 .", "al. 1998 . cit", "1998 . cit appears", ". cit appears to", "cit appears to phosphorylate", "appears to phosphorylate the", "to phosphorylate the myosin", "phosphorylate the myosin regulatory", "the myosin regulatory light", "myosin regulatory light chain", "light chain mrlc", "mrlc the", "the only substrate identified", "only substrate identified to", "substrate identified to date", "to date on", "date on the", "on the same residues", "the same residues that", "same residues that are", "residues that are phosphorylated", "that are phosphorylated by", "are phosphorylated by rocks", "by rocks but", "rocks but it", "but it has not", "it has not been", "has not been established", "not been established yet", "been established yet how", "established yet how this", "yet how this relates", "how this relates to", "this relates to activation", "relates to activation by", "to activation by rho", "activation by rho gtpases", "rho gtpases yamashiro", "gtpases yamashiro et", "yamashiro et al. 2003", "et al. 2003 .", "al. 2003 . cit", "2003 . cit and", ". cit and rhoa", "cit and rhoa are", "and rhoa are implicated", "rhoa are implicated to", "are implicated to act", "implicated to act together", "to act together in", "act together in golgi", "together in golgi apparatus", "in golgi apparatus organization", "golgi apparatus organization through", "apparatus organization through regulation", "organization through regulation of", "through regulation of the", "regulation of the actin", "of the actin cytoskeleton", "actin cytoskeleton camera", "cytoskeleton camera et", "camera et al. 2003", "2003 . cit is", ". cit is also", "cit is also involved", "is also involved in", "also involved in the", "involved in the regulation", "in the regulation of", "the regulation of cytokinesis", "regulation of cytokinesis through", "of cytokinesis through its", "cytokinesis through its interaction", "through its interaction with", "its interaction with kif14", "with kif14 gruneberg", "kif14 gruneberg et", "gruneberg et al. 2006", "al. 2006 bassi", "2006 bassi et", "bassi et al. 2013", "al. 2013 watanabe", "2013 watanabe et", "watanabe et al. 2013", "al. 2013 and", "2013 and p27", "kip1 serres", "serres et al. 2012", "et al. 2012 .", "kinase cit or", "cit or citron rho", "or citron rho interacting kinase", "rho interacting kinase crik", "kinase crik shares", "crik shares similarities with", "shares similarities with rock kinases.", "similarities with rock kinases. like", "with rock kinases. like rock", "kinases. like rock it", "like rock it consists", "rock it consists of", "it consists of a serine/threonine", "consists of a serine/threonine kinase", "of a serine/threonine kinase domain", "serine/threonine kinase domain a", "kinase domain a coiled", "domain a coiled coil", "coiled coil region a", "coil region a rho", "region a rho binding", "rho binding domain a", "binding domain a cysteine", "domain a cysteine rich", "a cysteine rich region and", "cysteine rich region and a", "rich region and a plekstrin", "region and a plekstrin homology", "a plekstrin homology ph", "homology ph domain", "ph domain but", "domain but additionally features", "but additionally features a proline", "additionally features a proline rich", "features a proline rich region", "a proline rich region and", "proline rich region and a", "rich region and a pdz", "region and a pdz binding", "and a pdz binding domain.", "a pdz binding domain. a", "pdz binding domain. a shorter", "binding domain. a shorter splicing", "domain. a shorter splicing isoform", "a shorter splicing isoform of", "shorter splicing isoform of cit", "isoform of cit citron", "of cit citron n", "citron n is specifically", "n is specifically expressed", "is specifically expressed in the", "specifically expressed in the nervous", "expressed in the nervous system", "in the nervous system and", "the nervous system and lacks", "nervous system and lacks the", "system and lacks the kinase", "and lacks the kinase domain.", "lacks the kinase domain. citron", "the kinase domain. citron n", "kinase domain. citron n is", "domain. citron n is a", "citron n is a component", "n is a component of", "is a component of the", "a component of the post", "component of the post synaptic", "of the post synaptic density", "post synaptic density where", "synaptic density where it", "density where it binds", "where it binds to the", "it binds to the pdz", "binds to the pdz domains", "to the pdz domains of", "the pdz domains of the", "pdz domains of the scaffolding", "domains of the scaffolding protein", "of the scaffolding protein pds", "the scaffolding protein pds 95/sap90", "protein pds 95/sap90 zhang", "pds 95/sap90 zhang et", "95/sap90 zhang et al.", "zhang et al. 2006 .

while", "et al. 2006 .

while the", "al. 2006 .

while the binding", "2006 .

while the binding of", ".

while the binding of cit", "the binding of cit to", "binding of cit to rho", "of cit to rho gtpases", "cit to rho gtpases rhoa", "rho gtpases rhoa rhob", "rhoa rhob rhoc", "rhob rhoc and rac1", "rhoc and rac1 is well", "and rac1 is well established", "is well established madaule", "well established madaule et", "established madaule et al.", "al. 1995 the", "1995 the mechanism", "the mechanism of cit activation", "mechanism of cit activation by", "of cit activation by gtp", "cit activation by gtp bound", "activation by gtp bound rho", "by gtp bound rho gtpases", "gtp bound rho gtpases has", "bound rho gtpases has not", "rho gtpases has not been", "gtpases has not been elucidated.", "has not been elucidated. there", "not been elucidated. there are", "been elucidated. there are indications", "elucidated. there are indications that", "there are indications that cit", "are indications that cit may", "indications that cit may be", "that cit may be activated", "cit may be activated through", "may be activated through autophosphorylation", "be activated through autophosphorylation in", "activated through autophosphorylation in the", "through autophosphorylation in the presence", "autophosphorylation in the presence of", "in the presence of active", "the presence of active forms", "presence of active forms of", "of active forms of rho", "active forms of rho gtpases", "of rho gtpases di", "rho gtpases di cunto", "gtpases di cunto et", "di cunto et al. 1998", "cunto et al. 1998 .", "et al. 1998 . cit", "al. 1998 . cit appears", "1998 . cit appears to", ". cit appears to phosphorylate", "cit appears to phosphorylate the", "appears to phosphorylate the myosin", "to phosphorylate the myosin regulatory", "phosphorylate the myosin regulatory light", "the myosin regulatory light chain", "regulatory light chain mrlc", "mrlc the only", "the only substrate identified to", "only substrate identified to date", "identified to date on", "to date on the", "date on the same", "on the same residues that", "the same residues that are", "same residues that are phosphorylated", "residues that are phosphorylated by", "that are phosphorylated by rocks", "phosphorylated by rocks but", "by rocks but it", "rocks but it has", "but it has not been", "it has not been established", "has not been established yet", "not been established yet how", "been established yet how this", "established yet how this relates", "yet how this relates to", "how this relates to activation", "this relates to activation by", "relates to activation by rho", "to activation by rho gtpases", "by rho gtpases yamashiro", "rho gtpases yamashiro et", "gtpases yamashiro et al.", "yamashiro et al. 2003 .", "et al. 2003 . cit", "al. 2003 . cit and", "2003 . cit and rhoa", ". cit and rhoa are", "cit and rhoa are implicated", "and rhoa are implicated to", "rhoa are implicated to act", "are implicated to act together", "implicated to act together in", "to act together in golgi", "act together in golgi apparatus", "together in golgi apparatus organization", "in golgi apparatus organization through", "golgi apparatus organization through regulation", "apparatus organization through regulation of", "organization through regulation of the", "through regulation of the actin", "regulation of the actin cytoskeleton", "the actin cytoskeleton camera", "actin cytoskeleton camera et", "cytoskeleton camera et al.", "camera et al. 2003 .", "al. 2003 . cit is", "2003 . cit is also", ". cit is also involved", "cit is also involved in", "is also involved in the", "also involved in the regulation", "involved in the regulation of", "in the regulation of cytokinesis", "the regulation of cytokinesis through", "regulation of cytokinesis through its", "of cytokinesis through its interaction", "cytokinesis through its interaction with", "through its interaction with kif14", "interaction with kif14 gruneberg", "with kif14 gruneberg et", "kif14 gruneberg et al.", "et al. 2006 bassi", "al. 2006 bassi et", "2006 bassi et al.", "et al. 2013 watanabe", "al. 2013 watanabe et", "2013 watanabe et al.", "et al. 2013 and", "al. 2013 and p27", "2013 and p27 kip1", "p27 kip1 serres", "kip1 serres et", "serres et al. 2012 ." ] }, { "record_id": "GLY_000594_1_465", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5626467", "r hsa", "hsa 5626467", "r hsa 5626467" ] }, { "record_id": "GLY_000594_1_465", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate iqgaps", "rho gtpases activate", "gtpases activate iqgaps", "rho gtpases activate iqgaps", "iqgaps constitute", "constitute a", "a family", "family of", "of scaffolding", "scaffolding proteins", "proteins characterized", "characterized by", "by a", "a calponin", "calponin homology", "a polyproline", "polyproline binding", "binding region", "ww domain", "a tandem", "tandem of", "of four", "four iq", "isoleucine and", "and glutamine", 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iqgap1", ".

iqgap1 is", "is involved", "involved in", "in the", "the regulation", "of adherens", "adherens junctions", "junctions through", "through its", "its interaction", "interaction with", "with e", "e cadherin", "and catenins", "cttnb1 and", "and cttna1", "al. 1998", "hage et", "al. 2009", "2009 .", ". iqgap1", "iqgap1 contributes", "contributes to", "to cell", "cell polarity", "polarity and", "and lamellipodia", "lamellipodia formation", "formation through", "with microtubules", "suzuki and", "and takahashi", "takahashi 2008", "2008 .", "iqgaps constitute a", "constitute a family", "a family of", "family of scaffolding", "of scaffolding proteins", "scaffolding proteins characterized", "proteins characterized by", "characterized by a", "by a calponin", "a calponin homology", "homology ch", "domain a", "a polyproline binding", "polyproline binding region", "region ww", "a tandem of", "tandem of four", "of four iq", "iq isoleucine", "isoleucine and glutamine", "and glutamine rich", "rich repeats", "repeats and a", "and a ras", "a ras gtpase", "ras gtpase activating", "gtpase activating protein", "activating protein related", "protein related domain", "domain grd", "grd . three", ". three iqgaps", "three iqgaps have", "iqgaps have been", "have been identified", "been identified in", "identified in human", "human iqgap1", "iqgap1 iqgap2", "iqgap2 and iqgap3.", "and iqgap3. the", "iqgap3. the best", "the best characterized", "best characterized is", "characterized is iqgap1", "is iqgap1 and", "iqgap1 and over", "and over 90", "over 90 proteins", "90 proteins have", "proteins have been", "have been reported", "been reported to", "reported to bind", "to bind to", "bind to it.", "to it. iqgaps", "it. iqgaps integrate", "iqgaps integrate multiple", "integrate multiple signaling", "multiple signaling pathways", "signaling pathways and", "pathways and coordinate", "and coordinate a", "coordinate a large", "a large variety", "large variety of", "variety of cellular", "of cellular activities", "activities white", "white et al.", "et al. 2012", "al. 2012 .", "2012 . iqgap", ". iqgap proteins", "iqgap proteins iqgap1", "iqgap2 and iqgap3", "iqgap3 bind", "bind activated rho", "activated rho gtpases", "rho gtpases rac1", "gtpases rac1 and", "rac1 and cdc42", "and cdc42 via", "cdc42 via their", "via their grd", "their grd and", "grd and stabilize", "and stabilize them", "stabilize them in", "them in their", "in their gtp", "their gtp bound", "gtp bound state", "state kuroda", "kuroda et al.", "et al. 1996", "1996 swart", "swart mataraza et", "mataraza et al.", "et al. 2002", "2002 wang", "wang et al.", "et al. 2007", "al. 2007 .", "2007 . iqgaps", ". iqgaps bind", "iqgaps bind f", "bind f actin", "f actin filaments", "actin filaments via", "filaments via the", "via the ch", "the ch domain", "ch domain and", "domain and modulate", "and modulate cell", "modulate cell shape", "cell shape and", "shape and motility", "and motility through", "motility through regulation", "through regulation of", "regulation of g", "of g actin/f", "g actin/f actin", "actin/f actin equilibrium", "equilibrium brill", "brill et al.", "1996 fukata", "fukata et al.", "et al. 1997", "1997 bashour", "bashour et al.", "1997 wang", "2007 pelikan", "pelikan conchaudron et", "conchaudron et al.", "et al. 2011", "al. 2011 .", "2011 . binding", ". binding of", "binding of iqgaps", "of iqgaps to", "iqgaps to f", "to f actin", "f actin is", "actin is inhibited", "is inhibited by", "inhibited by calmodulin", "by calmodulin binding", "calmodulin binding to", "binding to the", "to the iq", "the iq repeats", "repeats bashour", "1997 pelikan", "2011 . based", ". based on", "based on iqgap1", "on iqgap1 studies", "studies iqgaps", "iqgaps presumably function", "presumably function as", "function as homodimers", "homodimers bashour", "al. 1997 .

iqgap1", "1997 .

iqgap1 is", ".

iqgap1 is involved", "is involved in", "involved in the", "in the regulation", "the regulation of", "regulation of adherens", "of adherens junctions", "adherens junctions through", "junctions through its", "through its interaction", "its interaction with", "interaction with e", "with e cadherin", "cadherin cdh1", "cdh1 and", "catenins cttnb1", "cttnb1 and cttna1", "et al. 1998", "1998 hage", "hage et al.", "et al. 2009", "al. 2009 .", "2009 . iqgap1", ". iqgap1 contributes", "iqgap1 contributes to", "contributes to cell", "to cell polarity", "cell polarity and", "polarity and lamellipodia", "and lamellipodia formation", "lamellipodia formation through", "formation through its", "interaction with microtubules", "microtubules fukata", "2002 suzuki", "suzuki and takahashi", "and takahashi 2008", "takahashi 2008 .", "iqgaps constitute a family", "constitute a family of", "a family of scaffolding", "family of scaffolding proteins", "of scaffolding proteins characterized", "scaffolding proteins characterized by", "proteins characterized by a", "characterized by a calponin", "by a calponin homology", "calponin homology ch", "domain a polyproline", "a polyproline binding region", "binding region ww", "region ww domain", "a tandem of four", "tandem of four iq", "four iq isoleucine", "iq isoleucine and", "isoleucine and glutamine rich", "glutamine rich repeats", "rich repeats and", "repeats and a ras", "and a ras gtpase", "a ras gtpase activating", "ras gtpase activating protein", "gtpase activating protein related", "activating protein related domain", "related domain grd", "domain grd .", "grd . three iqgaps", ". three iqgaps have", "three iqgaps have been", "iqgaps have been identified", "have been identified in", "been identified in human", "in human iqgap1", "iqgap1 iqgap2 and", "iqgap2 and iqgap3. the", "and iqgap3. the best", "iqgap3. the best characterized", "the best characterized is", "best characterized is iqgap1", "characterized is iqgap1 and", "is iqgap1 and over", "iqgap1 and over 90", "and over 90 proteins", "over 90 proteins have", "90 proteins have been", "proteins have been reported", "have been reported to", "been reported to bind", "reported to bind to", "to bind to it.", "bind to it. iqgaps", "to it. iqgaps integrate", "it. iqgaps integrate multiple", "iqgaps integrate multiple signaling", "integrate multiple signaling pathways", "multiple signaling pathways and", "signaling pathways and coordinate", "pathways and coordinate a", "and coordinate a large", "coordinate a large variety", "a large variety of", "large variety of cellular", "variety of cellular activities", "cellular activities white", "activities white et", "white et al. 2012", "et al. 2012 .", "al. 2012 . iqgap", "2012 . iqgap proteins", ". iqgap proteins iqgap1", "proteins iqgap1 iqgap2", "and iqgap3 bind", "iqgap3 bind activated", "bind activated rho gtpases", "activated rho gtpases rac1", "rho gtpases rac1 and", "gtpases rac1 and cdc42", "rac1 and cdc42 via", "and cdc42 via their", "cdc42 via their grd", "via their grd and", "their grd and stabilize", "grd and stabilize them", "and stabilize them in", "stabilize them in their", "them in their gtp", "in their gtp bound", "their gtp bound state", "bound state kuroda", "state kuroda et", "kuroda et al. 1996", "al. 1996 swart", "1996 swart mataraza", "swart mataraza et al.", "mataraza et al. 2002", "al. 2002 wang", "2002 wang et", "wang et al. 2007", "et al. 2007 .", "al. 2007 . iqgaps", "2007 . iqgaps bind", ". iqgaps bind f", "iqgaps bind f actin", "bind f actin filaments", "f actin filaments via", "actin filaments via the", "filaments via the ch", "via the ch domain", "the ch domain and", "ch domain and modulate", "domain and modulate cell", "and modulate cell shape", "modulate cell shape and", "cell shape and motility", "shape and motility through", "and motility through regulation", "motility through regulation of", "through regulation of g", "regulation of g actin/f", "of g actin/f actin", "g actin/f actin equilibrium", "actin equilibrium brill", "equilibrium brill et", "brill et al. 1996", "al. 1996 fukata", "1996 fukata et", "fukata et al. 1997", "al. 1997 bashour", "1997 bashour et", "bashour et al. 1997", "al. 1997 wang", "1997 wang et", "al. 2007 pelikan", "2007 pelikan conchaudron", "pelikan conchaudron et al.", "conchaudron et al. 2011", "et al. 2011 .", "al. 2011 . binding", "2011 . binding of", ". binding of iqgaps", "binding of iqgaps to", "of iqgaps to f", "iqgaps to f actin", "to f actin is", "f actin is inhibited", "actin is inhibited by", "is inhibited by calmodulin", "inhibited by calmodulin binding", "by calmodulin binding to", "calmodulin binding to the", "binding to the iq", "to the iq repeats", "iq repeats bashour", "repeats bashour et", "al. 1997 pelikan", "1997 pelikan conchaudron", "al. 2011 . based", "2011 . based on", ". based on iqgap1", "based on iqgap1 studies", "iqgap1 studies iqgaps", "studies iqgaps presumably", "iqgaps presumably function as", "presumably function as homodimers", "as homodimers bashour", "homodimers bashour et", "et al. 1997 .

iqgap1", "al. 1997 .

iqgap1 is", "1997 .

iqgap1 is involved", ".

iqgap1 is involved in", "is involved in the", "involved in the regulation", "in the regulation of", "the regulation of adherens", "regulation of adherens junctions", "of adherens junctions through", "adherens junctions through its", "junctions through its interaction", "through its interaction with", "its interaction with e", "interaction with e cadherin", "e cadherin cdh1", "cdh1 and catenins", "and catenins cttnb1", "catenins cttnb1 and", "cttna1 kuroda", "kuroda et al. 1998", "al. 1998 hage", "1998 hage et", "hage et al. 2009", "et al. 2009 .", "al. 2009 . iqgap1", "2009 . iqgap1 contributes", ". iqgap1 contributes to", "iqgap1 contributes to cell", "contributes to cell polarity", "to cell polarity and", "cell polarity and lamellipodia", "polarity and lamellipodia formation", "and lamellipodia formation through", "lamellipodia formation through its", "formation through its interaction", "its interaction with microtubules", "with microtubules fukata", "microtubules fukata et", "fukata et al. 2002", "al. 2002 suzuki", "2002 suzuki and", "suzuki and takahashi 2008", "and takahashi 2008 .", "iqgaps constitute a family of", "constitute a family of scaffolding", "a family of scaffolding proteins", "family of scaffolding proteins characterized", "of scaffolding proteins characterized by", "scaffolding proteins characterized by a", "proteins characterized by a calponin", "characterized by a calponin homology", "a calponin homology ch", "homology ch domain", "ch domain a", "domain a polyproline binding", "polyproline binding region ww", "binding region ww domain", "ww domain a", "domain a tandem", "a tandem of four iq", "of four iq isoleucine", "four iq isoleucine and", "iq isoleucine and glutamine", "and glutamine rich repeats", "glutamine rich repeats and", "rich repeats and a", "repeats and a ras gtpase", "and a ras gtpase activating", "a ras gtpase activating protein", "ras gtpase activating protein related", "gtpase activating protein related domain", "protein related domain grd", "related domain grd .", "domain grd . three", "grd . three iqgaps have", ". three iqgaps have been", "three iqgaps have been identified", "iqgaps have been identified in", "have been identified in human", "identified in human iqgap1", "human iqgap1 iqgap2", "iqgap1 iqgap2 and iqgap3.", "iqgap2 and iqgap3. the best", "and iqgap3. the best characterized", "iqgap3. the best characterized is", "the best characterized is iqgap1", "best characterized is iqgap1 and", "characterized is iqgap1 and over", "is iqgap1 and over 90", "iqgap1 and over 90 proteins", "and over 90 proteins have", "over 90 proteins have been", "90 proteins have been reported", "proteins have been reported to", "have been reported to bind", "been reported to bind to", "reported to bind to it.", "to bind to it. iqgaps", "bind to it. iqgaps integrate", "to it. iqgaps integrate multiple", "it. iqgaps integrate multiple signaling", "iqgaps integrate multiple signaling pathways", "integrate multiple signaling pathways and", "multiple signaling pathways and coordinate", "signaling pathways and coordinate a", "pathways and coordinate a large", "and coordinate a large variety", "coordinate a large variety of", "a large variety of cellular", "large variety of cellular activities", "of cellular activities white", "cellular activities white et", "activities white et al.", "white et al. 2012 .", "et al. 2012 . iqgap", "al. 2012 . iqgap proteins", "2012 . iqgap proteins iqgap1", "iqgap proteins iqgap1 iqgap2", "proteins iqgap1 iqgap2 and", "iqgap1 iqgap2 and iqgap3", "iqgap2 and iqgap3 bind", "and iqgap3 bind activated", "iqgap3 bind activated rho", "bind activated rho gtpases rac1", "activated rho gtpases rac1 and", "rho gtpases rac1 and cdc42", "gtpases rac1 and cdc42 via", "rac1 and cdc42 via their", "and cdc42 via their grd", "cdc42 via their grd and", "via their grd and stabilize", "their grd and stabilize them", "grd and stabilize them in", "and stabilize them in their", "stabilize them in their gtp", "them in their gtp bound", "in their gtp bound state", "gtp bound state kuroda", "bound state kuroda et", "state kuroda et al.", "et al. 1996 swart", "al. 1996 swart mataraza", "1996 swart mataraza et", "swart mataraza et al. 2002", "et al. 2002 wang", "al. 2002 wang et", "2002 wang et al.", "wang et al. 2007 .", "et al. 2007 . iqgaps", "al. 2007 . iqgaps bind", "2007 . iqgaps bind f", ". iqgaps bind f actin", "iqgaps bind f actin filaments", "bind f actin filaments via", "f actin filaments via the", "actin filaments via the ch", "filaments via the ch domain", "via the ch domain and", "the ch domain and modulate", "ch domain and modulate cell", "domain and modulate cell shape", "and modulate cell shape and", "modulate cell shape and motility", "cell shape and motility through", "shape and motility through regulation", "and motility through regulation of", "motility through regulation of g", "through regulation of g actin/f", "regulation of g actin/f actin", "of g actin/f actin equilibrium", "actin/f actin equilibrium brill", "actin equilibrium brill et", "equilibrium brill et al.", "et al. 1996 fukata", "al. 1996 fukata et", "1996 fukata et al.", "et al. 1997 bashour", "al. 1997 bashour et", "1997 bashour et al.", "et al. 1997 wang", "al. 1997 wang et", "1997 wang et al.", "et al. 2007 pelikan", "al. 2007 pelikan conchaudron", "2007 pelikan conchaudron et", "pelikan conchaudron et al. 2011", "conchaudron et al. 2011 .", "et al. 2011 . binding", "al. 2011 . binding of", "2011 . binding of iqgaps", ". binding of iqgaps to", "binding of iqgaps to f", "of iqgaps to f actin", "iqgaps to f actin is", "to f actin is inhibited", "f actin is inhibited by", "actin is inhibited by calmodulin", "is inhibited by calmodulin binding", "inhibited by calmodulin binding to", "by calmodulin binding to the", "calmodulin binding to the iq", "binding to the iq repeats", "the iq repeats bashour", "iq repeats bashour et", "repeats bashour et al.", "et al. 1997 pelikan", "al. 1997 pelikan conchaudron", "1997 pelikan conchaudron et", "et al. 2011 . based", "al. 2011 . based on", "2011 . based on iqgap1", ". based on iqgap1 studies", "on iqgap1 studies iqgaps", "iqgap1 studies iqgaps presumably", "studies iqgaps presumably function", "iqgaps presumably function as homodimers", "function as homodimers bashour", "as homodimers bashour et", "homodimers bashour et al.", "bashour et al. 1997 .

iqgap1", "et al. 1997 .

iqgap1 is", "al. 1997 .

iqgap1 is involved", "1997 .

iqgap1 is involved in", ".

iqgap1 is involved in the", "is involved in the regulation", "involved in the regulation of", "in the regulation of adherens", "the regulation of adherens junctions", "regulation of adherens junctions through", "of adherens junctions through its", "adherens junctions through its interaction", "junctions through its interaction with", "through its interaction with e", "its interaction with e cadherin", "with e cadherin cdh1", "cadherin cdh1 and", "and catenins cttnb1 and", "catenins cttnb1 and cttna1", "and cttna1 kuroda", "cttna1 kuroda et", "et al. 1998 hage", "al. 1998 hage et", "1998 hage et al.", "hage et al. 2009 .", "et al. 2009 . iqgap1", "al. 2009 . iqgap1 contributes", "2009 . iqgap1 contributes to", ". iqgap1 contributes to cell", "iqgap1 contributes to cell polarity", "contributes to cell polarity and", "to cell polarity and lamellipodia", "cell polarity and lamellipodia formation", "polarity and lamellipodia formation through", "and lamellipodia formation through its", "lamellipodia formation through its interaction", "formation through its interaction with", "through its interaction with microtubules", "interaction with microtubules fukata", "with microtubules fukata et", "microtubules fukata et al.", "et al. 2002 suzuki", "al. 2002 suzuki and", "2002 suzuki and takahashi", "suzuki and takahashi 2008 ." ] }, { "record_id": "GLY_000594_1_466", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5627117", "r hsa", "hsa 5627117", "r hsa 5627117" ] }, { "record_id": "GLY_000594_1_466", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate rocks", "rho gtpases activate", "gtpases activate rocks", "rho gtpases activate rocks", "rho associated", "coiled coil", "coil containing", "containing protein", "protein kinases", "kinases rock1", "rock1 and", "and rock2", "rock2 consist", "consist of", "of a", "a serine/threonine", "serine/threonine kinase", "kinase domain", "a coiled", "coil region", "a rho", "rho binding", "binding domain", "domain and", "and a", "a plekstrin", "plekstrin homology", "domain interspersed", "interspersed with", "with a", "a cysteine", "cysteine rich", "rich region.", "region. the", "the ph", "ph domain", "domain inhibits", "inhibits the", "the kinase", "kinase activity", "activity of", "of rocks", "rocks by", "by an", "an intramolecular", "intramolecular fold.", "fold. rocks", "rocks are", "are activated", "activated by", "by binding", "binding of", "of the", "the gtp", "gtp bound", "bound rho", "gtpases rhoa", "rhob and", "and rhoc", "rhoc to", "to the", "the rho", "domain of", "ishizaki et", "et al.", "al. 1996", "leung et", "which disrupts", "disrupts the", "the autoinhibitory", "autoinhibitory fold.", "fold. once", "once activated", "rock2 phosphorylate", "phosphorylate target", "target proteins", "many of", "of which", "which are", "are involved", "involved in", "in the", "the stabilization", "stabilization of", "of actin", "actin filaments", "filaments and", "and generation", "generation of", "actin myosin", "myosin contractile", "contractile force.", "force. rocks", "rocks phosphorylate", "phosphorylate lim", "lim kinases", "kinases limk1", "limk1 and", "and limk2", "enabling limks", "limks to", "to phosphorylate", "phosphorylate cofilin", "an actin", "actin depolymerizing", "depolymerizing factor", "and thereby", "thereby regulate", "regulate the", "the reorganization", "reorganization of", "the actin", "actin cytoskeleton", "ohashi et", "al. 2000", "sumi et", "al. 2001", "2001 .", ". rocks", "phosphorylate mrlc", "myosin regulatory", "regulatory light", "light chain", "which stimulates", "stimulates the", "the activity", "of non", "non muscle", "muscle myosin", "myosin ii", "actin based", "based motor", "motor protein", "protein involved", "in cell", "cell migration", "polarity formation", "formation and", "and cytokinesis", "amano et", "riento and", "and ridley", "ridley 2003", "watanabe et", "al. 2007", "al. 2010", "2010 .", "rocks also", "also phosphorylate", "phosphorylate the", "the myosin", "myosin phosphatase", "phosphatase targeting", "targeting subunit", "of mlc", "mlc phosphatase", "inhibiting the", "the phosphatase", "phosphatase activity", "activity and", "and preventing", "preventing dephosphorylation", "dephosphorylation of", "of mrlc.", "mrlc. this", "this pathway", "pathway acts", "acts synergistically", "synergistically with", "with phosphorylation", "phosphorylation of", "of mrlc", "mrlc by", "by rocks", "rocks towards", "towards stimulation", "stimulation of", "ii activity", "kimura et", "associated coiled", "coiled coil containing", "coil containing protein", "containing protein kinases", "protein kinases rock1", "kinases rock1 and", "rock1 and rock2", "and rock2 consist", "rock2 consist of", "consist of a", "of a serine/threonine", "a serine/threonine kinase", "serine/threonine kinase domain", "domain a", "a coiled coil", "coiled coil region", "region a", "a rho binding", "rho binding domain", "binding domain and", "domain and a", "and a plekstrin", "a plekstrin homology", "homology ph", "domain interspersed with", "interspersed with a", "with a cysteine", "a cysteine rich", "cysteine rich region.", "rich region. the", "region. the ph", "the ph domain", "ph domain inhibits", "domain inhibits the", "inhibits the kinase", "the kinase activity", "kinase activity of", "activity of rocks", "of rocks by", "rocks by an", "by an intramolecular", "an intramolecular fold.", "intramolecular fold. rocks", "fold. rocks are", "rocks are activated", "are activated by", "activated by binding", "by binding of", "binding of the", "of the gtp", "the gtp bound", "gtp bound rho", "bound rho gtpases", "rho gtpases rhoa", "rhoa rhob", "rhob and rhoc", "and rhoc to", "rhoc to the", "to the rho", "the rho binding", "binding domain of", "domain of rocks", "rocks ishizaki", "ishizaki et al.", "et al. 1996", "1996 leung", "leung et al.", "which disrupts the", "disrupts the autoinhibitory", "the autoinhibitory fold.", "autoinhibitory fold. once", "fold. once activated", "activated rock1", "and rock2 phosphorylate", "rock2 phosphorylate target", "phosphorylate target proteins", "proteins many", "many of which", "of which are", "which are involved", "are involved in", "involved in the", "in the stabilization", "the stabilization of", "stabilization of actin", "of actin filaments", "actin filaments and", "filaments and generation", "and generation of", "generation of actin", "of actin myosin", "actin myosin contractile", "myosin contractile force.", "contractile force. rocks", "force. rocks phosphorylate", "rocks phosphorylate lim", "phosphorylate lim kinases", "lim kinases limk1", "kinases limk1 and", "limk1 and limk2", "limk2 enabling", "enabling limks to", "limks to phosphorylate", "to phosphorylate cofilin", "cofilin an", "an actin depolymerizing", "actin depolymerizing factor", "factor and", "and thereby regulate", "thereby regulate the", "regulate the reorganization", "the reorganization of", "reorganization of the", "of the actin", "the actin cytoskeleton", "cytoskeleton ohashi", "ohashi et al.", "et al. 2000", "2000 sumi", "sumi et al.", "et al. 2001", "al. 2001 .", "2001 . rocks", ". rocks phosphorylate", "rocks phosphorylate mrlc", "mrlc myosin", "myosin regulatory light", "regulatory light chain", "which stimulates the", "stimulates the activity", "the activity of", "activity of non", "of non muscle", "non muscle myosin", "muscle myosin ii", "ii nmm2", "an actin based", "actin based motor", "based motor protein", "motor protein involved", "protein involved in", "involved in cell", "in cell migration", "migration polarity", "polarity formation and", "formation and cytokinesis", "cytokinesis amano", "amano et al.", "1996 riento", "riento and ridley", "and ridley 2003", "2003 watanabe", "watanabe et al.", "et al. 2007", "2007 amano", "et al. 2010", "al. 2010 .", "2010 . rocks", ". rocks also", "rocks also phosphorylate", "also phosphorylate the", "phosphorylate the myosin", "the myosin phosphatase", "myosin phosphatase targeting", "phosphatase targeting subunit", "subunit mypt1", "mypt1 of", "of mlc phosphatase", "phosphatase inhibiting", "inhibiting the phosphatase", "the phosphatase activity", "phosphatase activity and", "activity and preventing", "and preventing dephosphorylation", "preventing dephosphorylation of", "dephosphorylation of mrlc.", "of mrlc. this", "mrlc. this pathway", "this pathway acts", "pathway acts synergistically", "acts synergistically with", "synergistically with phosphorylation", "with phosphorylation of", "phosphorylation of mrlc", "of mrlc by", "mrlc by rocks", "by rocks towards", "rocks towards stimulation", "towards stimulation of", "stimulation of non", "myosin ii activity", "activity kimura", "kimura et al.", "1996 amano", "rho associated coiled", "associated coiled coil", "coiled coil containing protein", "coil containing protein kinases", "containing protein kinases rock1", "protein kinases rock1 and", "kinases rock1 and rock2", "rock1 and rock2 consist", "and rock2 consist of", "rock2 consist of a", "consist of a serine/threonine", "of a serine/threonine kinase", "a serine/threonine kinase domain", "kinase domain a", "domain a coiled", "a coiled coil region", "coil region a", "region a rho", "a rho binding domain", "rho binding domain and", "binding domain and a", "domain and a plekstrin", "and a plekstrin homology", "plekstrin homology ph", "ph domain interspersed", "domain interspersed with a", "interspersed with a cysteine", "with a cysteine rich", "a cysteine rich region.", "cysteine rich region. the", "rich region. the ph", "region. the ph domain", "the ph domain inhibits", "ph domain inhibits the", "domain inhibits the kinase", "inhibits the kinase activity", "the kinase activity of", "kinase activity of rocks", "activity of rocks by", "of rocks by an", "rocks by an intramolecular", "by an intramolecular fold.", "an intramolecular fold. rocks", "intramolecular fold. rocks are", "fold. rocks are activated", "rocks are activated by", "are activated by binding", "activated by binding of", "by binding of the", "binding of the gtp", "of the gtp bound", "the gtp bound rho", "gtp bound rho gtpases", "bound rho gtpases rhoa", "gtpases rhoa rhob", "rhoa rhob and", "rhob and rhoc to", "and rhoc to the", "rhoc to the rho", "to the rho binding", "the rho binding domain", "rho binding domain of", "binding domain of rocks", "of rocks ishizaki", "rocks ishizaki et", "ishizaki et al. 1996", "al. 1996 leung", "1996 leung et", "leung et al. 1996", "1996 which", "which disrupts the autoinhibitory", "disrupts the autoinhibitory fold.", "the autoinhibitory fold. once", "autoinhibitory fold. once activated", "once activated rock1", "activated rock1 and", "rock1 and rock2 phosphorylate", "and rock2 phosphorylate target", "rock2 phosphorylate target proteins", "target proteins many", "proteins many of", "many of which are", "of which are involved", "which are involved in", "are involved in the", "involved in the stabilization", "in the stabilization of", "the stabilization of actin", "stabilization of actin filaments", "of actin filaments and", "actin filaments and generation", "filaments and generation of", "and generation of actin", "generation of actin myosin", "of actin myosin contractile", "actin myosin contractile force.", "myosin contractile force. rocks", "contractile force. rocks phosphorylate", "force. rocks phosphorylate lim", "rocks phosphorylate lim kinases", "phosphorylate lim kinases limk1", "lim kinases limk1 and", "kinases limk1 and limk2", "and limk2 enabling", "limk2 enabling limks", "enabling limks to phosphorylate", "limks to phosphorylate cofilin", "phosphorylate cofilin an", "cofilin an actin", "an actin depolymerizing factor", "depolymerizing factor and", "factor and thereby", "and thereby regulate the", "thereby regulate the reorganization", "regulate the reorganization of", "the reorganization of the", "reorganization of the actin", "of the actin cytoskeleton", "actin cytoskeleton ohashi", "cytoskeleton ohashi et", "ohashi et al. 2000", "al. 2000 sumi", "2000 sumi et", "sumi et al. 2001", "et al. 2001 .", "al. 2001 . rocks", "2001 . rocks phosphorylate", ". rocks phosphorylate mrlc", "phosphorylate mrlc myosin", "mrlc myosin regulatory", "myosin regulatory light chain", "chain which", "which stimulates the activity", "stimulates the activity of", "the activity of non", "activity of non muscle", "of non muscle myosin", "non muscle myosin ii", "myosin ii nmm2", "nmm2 an", "an actin based motor", "actin based motor protein", "based motor protein involved", "motor protein involved in", "protein involved in cell", "involved in cell migration", "cell migration polarity", "migration polarity formation", "polarity formation and cytokinesis", "and cytokinesis amano", "cytokinesis amano et", "amano et al. 1996", "al. 1996 riento", "1996 riento and", "riento and ridley 2003", "ridley 2003 watanabe", "2003 watanabe et", "watanabe et al. 2007", "al. 2007 amano", "2007 amano et", "amano et al. 2010", "et al. 2010 .", "al. 2010 . rocks", "2010 . rocks also", ". rocks also phosphorylate", "rocks also phosphorylate the", "also phosphorylate the myosin", "phosphorylate the myosin phosphatase", "the myosin phosphatase targeting", "myosin phosphatase targeting subunit", "targeting subunit mypt1", "mypt1 of mlc", "mlc phosphatase inhibiting", "phosphatase inhibiting the", "inhibiting the phosphatase activity", "the phosphatase activity and", "phosphatase activity and preventing", "activity and preventing dephosphorylation", "and preventing dephosphorylation of", "preventing dephosphorylation of mrlc.", "dephosphorylation of mrlc. this", "of mrlc. this pathway", "mrlc. this pathway acts", "this pathway acts synergistically", "pathway acts synergistically with", "acts synergistically with phosphorylation", "synergistically with phosphorylation of", "with phosphorylation of mrlc", "phosphorylation of mrlc by", "of mrlc by rocks", "mrlc by rocks towards", "by rocks towards stimulation", "rocks towards stimulation of", "towards stimulation of non", "stimulation of non muscle", "muscle myosin ii activity", "ii activity kimura", "activity kimura et", "kimura et al. 1996", "al. 1996 amano", "1996 amano et", "rho associated coiled coil", "associated coiled coil containing", "coiled coil containing protein kinases", "coil containing protein kinases rock1", "containing protein kinases rock1 and", "protein kinases rock1 and rock2", "kinases rock1 and rock2 consist", "rock1 and rock2 consist of", "and rock2 consist of a", "rock2 consist of a serine/threonine", "consist of a serine/threonine kinase", "of a serine/threonine kinase domain", "serine/threonine kinase domain a", "kinase domain a coiled", "domain a coiled coil", "coiled coil region a", "coil region a rho", "region a rho binding", "a rho binding domain and", "rho binding domain and a", "binding domain and a plekstrin", "domain and a plekstrin homology", "a plekstrin homology ph", "homology ph domain", "ph domain interspersed with", "domain interspersed with a cysteine", "interspersed with a cysteine rich", "with a cysteine rich region.", "a cysteine rich region. the", "cysteine rich region. the ph", "rich region. the ph domain", "region. the ph domain inhibits", "the ph domain inhibits the", "ph domain inhibits the kinase", "domain inhibits the kinase activity", "inhibits the kinase activity of", "the kinase activity of rocks", "kinase activity of rocks by", "activity of rocks by an", "of rocks by an intramolecular", "rocks by an intramolecular fold.", "by an intramolecular fold. rocks", "an intramolecular fold. rocks are", "intramolecular fold. rocks are activated", "fold. rocks are activated by", "rocks are activated by binding", "are activated by binding of", "activated by binding of the", "by binding of the gtp", "binding of the gtp bound", "of the gtp bound rho", "the gtp bound rho gtpases", "gtp bound rho gtpases rhoa", "rho gtpases rhoa rhob", "gtpases rhoa rhob and", "rhoa rhob and rhoc", "rhob and rhoc to the", "and rhoc to the rho", "rhoc to the rho binding", "to the rho binding domain", "the rho binding domain of", "rho binding domain of rocks", "domain of rocks ishizaki", "of rocks ishizaki et", "rocks ishizaki et al.", "et al. 1996 leung", "al. 1996 leung et", "1996 leung et al.", "al. 1996 which", "1996 which disrupts", "which disrupts the autoinhibitory fold.", "disrupts the autoinhibitory fold. once", "the autoinhibitory fold. once activated", "fold. once activated rock1", "once activated rock1 and", "activated rock1 and rock2", "rock1 and rock2 phosphorylate target", "and rock2 phosphorylate target proteins", "phosphorylate target proteins many", "target proteins many of", "proteins many of which", "many of which are involved", "of which are involved in", "which are involved in the", "are involved in the stabilization", "involved in the stabilization of", "in the stabilization of actin", "the stabilization of actin filaments", "stabilization of actin filaments and", "of actin filaments and generation", "actin filaments and generation of", "filaments and generation of actin", "and generation of actin myosin", "generation of actin myosin contractile", "of actin myosin contractile force.", "actin myosin contractile force. rocks", "myosin contractile force. rocks phosphorylate", "contractile force. rocks phosphorylate lim", "force. rocks phosphorylate lim kinases", "rocks phosphorylate lim kinases limk1", "phosphorylate lim kinases limk1 and", "lim kinases limk1 and limk2", "limk1 and limk2 enabling", "and limk2 enabling limks", "limk2 enabling limks to", "enabling limks to phosphorylate cofilin", "to phosphorylate cofilin an", "phosphorylate cofilin an actin", "cofilin an actin depolymerizing", "actin depolymerizing factor and", "depolymerizing factor and thereby", "factor and thereby regulate", "and thereby regulate the reorganization", "thereby regulate the reorganization of", "regulate the reorganization of the", "the reorganization of the actin", "reorganization of the actin cytoskeleton", "the actin cytoskeleton ohashi", "actin cytoskeleton ohashi et", "cytoskeleton ohashi et al.", "et al. 2000 sumi", "al. 2000 sumi et", "2000 sumi et al.", "sumi et al. 2001 .", "et al. 2001 . rocks", "al. 2001 . rocks phosphorylate", "2001 . rocks phosphorylate mrlc", "rocks phosphorylate mrlc myosin", "phosphorylate mrlc myosin regulatory", "mrlc myosin regulatory light", "light chain which", "chain which stimulates", "which stimulates the activity of", "stimulates the activity of non", "the activity of non muscle", "activity of non muscle myosin", "of non muscle myosin ii", "muscle myosin ii nmm2", "nmm2 an actin", "an actin based motor protein", "actin based motor protein involved", "based motor protein involved in", "motor protein involved in cell", "protein involved in cell migration", "in cell migration polarity", "cell migration polarity formation", "migration polarity formation and", "formation and cytokinesis amano", "and cytokinesis amano et", "cytokinesis amano et al.", "et al. 1996 riento", "al. 1996 riento and", "1996 riento and ridley", "and ridley 2003 watanabe", "ridley 2003 watanabe et", "2003 watanabe et al.", "et al. 2007 amano", "al. 2007 amano et", "2007 amano et al.", "amano et al. 2010 .", "et al. 2010 . rocks", "al. 2010 . rocks also", "2010 . rocks also phosphorylate", ". rocks also phosphorylate the", "rocks also phosphorylate the myosin", "also phosphorylate the myosin phosphatase", "phosphorylate the myosin phosphatase targeting", "the myosin phosphatase targeting subunit", "phosphatase targeting subunit mypt1", "subunit mypt1 of", "mypt1 of mlc phosphatase", "of mlc phosphatase inhibiting", "mlc phosphatase inhibiting the", "phosphatase inhibiting the phosphatase", "inhibiting the phosphatase activity and", "the phosphatase activity and preventing", "phosphatase activity and preventing dephosphorylation", "activity and preventing dephosphorylation of", "and preventing dephosphorylation of mrlc.", "preventing dephosphorylation of mrlc. this", "dephosphorylation of mrlc. this pathway", "of mrlc. this pathway acts", "mrlc. this pathway acts synergistically", "this pathway acts synergistically with", "pathway acts synergistically with phosphorylation", "acts synergistically with phosphorylation of", "synergistically with phosphorylation of mrlc", "with phosphorylation of mrlc by", "phosphorylation of mrlc by rocks", "of mrlc by rocks towards", "mrlc by rocks towards stimulation", "by rocks towards stimulation of", "rocks towards stimulation of non", "towards stimulation of non muscle", "stimulation of non muscle myosin", "non muscle myosin ii activity", "myosin ii activity kimura", "ii activity kimura et", "activity kimura et al.", "et al. 1996 amano", "al. 1996 amano et", "1996 amano et al." ] }, { "record_id": "GLY_000594_1_467", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5627123", "r hsa", "hsa 5627123", "r hsa 5627123" ] }, { "record_id": "GLY_000594_1_467", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate paks", "rho gtpases activate", "gtpases activate paks", "rho gtpases activate paks", "the paks", "p21 activated", "activated kinases", "are a", "a family", "family of", "of serine/threonine", "serine/threonine kinases", "kinases mainly", "mainly implicated", "implicated in", "in cytoskeletal", "cytoskeletal rearrangements.", "rearrangements. all", "all paks", "paks share", "share a", "a conserved", "conserved catalytic", "catalytic domain", "domain located", "located at", "at the", "the carboxyl", "carboxyl terminus", "terminus and", "and a", "a highly", "highly conserved", "conserved motif", "motif in", "in the", "the amino", "amino terminus", "terminus known", "known as", "as p21", "p21 binding", "binding domain", "or cdc42/rac", "cdc42/rac interactive", "interactive binding", "domain. there", "there are", "are six", "six mammalian", "mammalian paks", "paks that", "that can", "can be", "be divided", "divided into", "into two", "two classes:", "classes: class", "class i", "or conventional", "pak1 3", "and class", "class ii", "ii paks", "pak4 6", "6 .", ". conventional", "conventional paks", "paks are", "are important", "important regulators", "regulators of", "of cytoskeletal", "cytoskeletal dynamics", "dynamics and", "and cell", "cell motility", "motility and", "and are", "are additionally", "additionally implicated", "in transcription", "transcription through", "through mapk", "mitogen activated", "activated protein", "protein kinase", "death and", "and survival", "survival signaling", "signaling and", "cell cycle", "cycle progression", "chan and", "and manser", "manser 2012", "2012 .

pak1", "pak2 and", "and pak3", "pak3 are", "are direct", "direct effectors", "effectors of", "of rac1", "rac1 and", "and cdc42", "cdc42 gtpases.", "gtpases. rac1", "cdc42 bind", "bind to", "to the", "the crib", "crib domain.", "domain. this", "this binding", "binding induces", "induces a", "a conformational", "conformational change", "change that", "that disrupts", "disrupts inactive", "inactive pak", "pak homodimers", "homodimers and", "and relieves", "relieves autoinhibition", "autoinhibition of", "of the", "the catalytic", "catalytic carboxyl", "carboxyl terminal", "terminal domain", "manser et", "et al.", "al. 1994", "al. 1995", "zhang et", "al. 1998", "lei et", "al. 2000", "parrini et", "al. 2002", "reviewed by", "by daniels", "daniels and", "and bokoch", "bokoch 1999", "szczepanowska 2009", "2009 .", ". autophosphorylation", "autophosphorylation of", "of a", "conserved threonine", "threonine residue", "residue in", "domain of", "of paks", "t423 in", "in pak1", "t402 in", "in pak2", "and t436", "t436 in", "in pak3", "is necessary", "necessary for", "for the", "the kinase", "kinase activity", "activity of", "of pak1", "and pak3.", "pak3. autophosphorylation", "pak1 serine", "serine residue", "residue s144", "pak2 serine", "residue s141", "pak3 serine", "residue s154", "s154 disrupts", "disrupts association", "association of", "paks with", "with rac1", "rac1 or", "or cdc42", "cdc42 and", "and enhances", "enhances kinase", "chong et", "al. 2001", "jung and", "and traugh", "traugh 2005", "wang et", "al. 2011", "2011 .", ". limk1", "limk1 is", "is one", "one of", "the downstream", "downstream targets", "targets of", "pak1 and", "and is", "is activated", "activated through", "through pak1", "pak1 mediated", "mediated phosphorylation", "phosphorylation of", "the threonine", "residue t508", "t508 within", "within its", "its activation", "activation loop", "edwards et", "al. 1999", "1999 .", ". further", "further targets", "targets are", "are the", "the myosin", "myosin regulatory", "regulatory light", "light chain", "myosin light", "chain kinase", "a subunit", "subunit of", "the arp2/3", "arp2/3 complex", "paxillin and", "and rhogdi", "to mention", "mention a", "a few", "2009 .

class", ".

class ii", "paks also", "also have", "have a", "a crib", "crib domain", "but lack", "lack a", "a defined", "defined autoinhibitory", "autoinhibitory domain", "domain and", "and proline", "proline rich", "rich regions.", "regions. they", "they do", "do not", "not require", "require gtpases", "gtpases for", "for their", "their kinase", "but their", "their interaction", "interaction with", "with rac", "rac or", "cdc42 affects", "affects their", "their subcellular", "subcellular localization.", "localization. only", "only conventional", "paks will", "will be", "be annotated", "annotated here.", "paks p21", "p21 activated kinases", "kinases are", "are a family", "a family of", "family of serine/threonine", "of serine/threonine kinases", "serine/threonine kinases mainly", "kinases mainly implicated", "mainly implicated in", "implicated in cytoskeletal", "in cytoskeletal rearrangements.", "cytoskeletal rearrangements. all", "rearrangements. all paks", "all paks share", "paks share a", "share a conserved", "a conserved catalytic", "conserved catalytic domain", "catalytic domain located", "domain located at", "located at the", "at the carboxyl", "the carboxyl terminus", "carboxyl terminus and", "terminus and a", "and a highly", "a highly conserved", "highly conserved motif", "conserved motif in", "motif in the", "in the amino", "the amino terminus", "amino terminus known", "terminus known as", "known as p21", "as p21 binding", "p21 binding domain", "domain pbd", "pbd or", "or cdc42/rac interactive", "cdc42/rac interactive binding", "binding crib", "domain. there are", "there are six", "are six mammalian", "six mammalian paks", "mammalian paks that", "paks that can", "that can be", "can be divided", "be divided into", "divided into two", "into two classes:", "two classes: class", "classes: class i", "i or", "paks pak1", "3 and", "and class ii", "class ii paks", "paks pak4", "pak4 6 .", "6 . conventional", ". conventional paks", "conventional paks are", "paks are important", "are important regulators", "important regulators of", "regulators of cytoskeletal", "of cytoskeletal dynamics", "cytoskeletal dynamics and", "dynamics and cell", "and cell motility", "cell motility and", "motility and are", "and are additionally", "are additionally implicated", "additionally implicated in", "implicated in transcription", "in transcription through", "transcription through mapk", "mapk mitogen", "mitogen activated protein", "activated protein kinase", "kinase cascades", "cascades death", "death and survival", "and survival signaling", "survival signaling and", "signaling and cell", "and cell cycle", "cell cycle progression", "progression chan", "chan and manser", "and manser 2012", "manser 2012 .

pak1", ".

pak1 pak2", "pak2 and pak3", "and pak3 are", "pak3 are direct", "are direct effectors", "direct effectors of", "effectors of rac1", "of rac1 and", "rac1 and cdc42", "and cdc42 gtpases.", "cdc42 gtpases. rac1", "gtpases. rac1 and", "and cdc42 bind", "cdc42 bind to", "bind to the", "to the crib", "the crib domain.", "crib domain. this", "domain. this binding", "this binding induces", "binding induces a", "induces a conformational", "a conformational change", "conformational change that", "change that disrupts", "that disrupts inactive", "disrupts inactive pak", "inactive pak homodimers", "pak homodimers and", "homodimers and relieves", "and relieves autoinhibition", "relieves autoinhibition of", "autoinhibition of the", "of the catalytic", "the catalytic carboxyl", "catalytic carboxyl terminal", "carboxyl terminal domain", "domain manser", "manser et al.", "et al. 1994", "1994 manser", "et al. 1995", "1995 zhang", "zhang et al.", "et al. 1998", "1998 lei", "lei et al.", "et al. 2000", "2000 parrini", "parrini et al.", "et al. 2002", "2002 reviewed", "reviewed by daniels", "by daniels and", "daniels and bokoch", "and bokoch 1999", "1999 szczepanowska", "szczepanowska 2009 .", "2009 . autophosphorylation", ". autophosphorylation of", "autophosphorylation of a", "of a conserved", "a conserved threonine", "conserved threonine residue", "threonine residue in", "residue in the", "in the catalytic", "the catalytic domain", "catalytic domain of", "domain of paks", "paks t423", "t423 in pak1", "pak1 t402", "t402 in pak2", "in pak2 and", "pak2 and t436", "and t436 in", "t436 in pak3", "pak3 is", "is necessary for", "necessary for the", "for the kinase", "the kinase activity", "kinase activity of", "activity of pak1", "pak1 pak2", "pak2 and pak3.", "and pak3. autophosphorylation", "pak3. autophosphorylation of", "autophosphorylation of pak1", "of pak1 serine", "pak1 serine residue", "serine residue s144", "s144 pak2", "pak2 serine residue", "serine residue s141", "s141 and", "and pak3 serine", "pak3 serine residue", "serine residue s154", "residue s154 disrupts", "s154 disrupts association", "disrupts association of", "association of paks", "of paks with", "paks with rac1", "with rac1 or", "rac1 or cdc42", "or cdc42 and", "cdc42 and enhances", "and enhances kinase", "enhances kinase activity", "activity lei", "2000 chong", "chong et al.", "et al. 2001", "2001 parrini", "2002 jung", "jung and traugh", "and traugh 2005", "2005 wang", "wang et al.", "et al. 2011", "al. 2011 .", "2011 . limk1", ". limk1 is", "limk1 is one", "is one of", "one of the", "of the downstream", "the downstream targets", "downstream targets of", "targets of pak1", "of pak1 and", "pak1 and is", "and is activated", "is activated through", "activated through pak1", "through pak1 mediated", "pak1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of the", "of the threonine", "the threonine residue", "threonine residue t508", "residue t508 within", "t508 within its", "within its activation", "its activation loop", "loop edwards", "edwards et al.", "et al. 1999", "al. 1999 .", "1999 . further", ". further targets", "further targets are", "targets are the", "are the myosin", "the myosin regulatory", "myosin regulatory light", "regulatory light chain", "chain mrlc", "myosin light chain", "light chain kinase", "kinase mlck", "filamin cortactin", "cortactin p41arc", "p41arc a", "a subunit of", "subunit of the", "of the arp2/3", "the arp2/3 complex", "caldesmon paxillin", "paxillin and rhogdi", "rhogdi to", "to mention a", "mention a few", "few szczepanowska", "szczepanowska 2009 .

class", "2009 .

class ii", ".

class ii paks", "ii paks also", "paks also have", "also have a", "have a crib", "a crib domain", "domain but", "but lack a", "lack a defined", "a defined autoinhibitory", "defined autoinhibitory domain", "autoinhibitory domain and", "domain and proline", "and proline rich", "proline rich regions.", "rich regions. they", "regions. they do", "they do not", "do not require", "not require gtpases", "require gtpases for", "gtpases for their", "for their kinase", "their kinase activity", "activity but", "but their interaction", "their interaction with", "interaction with rac", "with rac or", "rac or cdc42", "or cdc42 affects", "cdc42 affects their", "affects their subcellular", "their subcellular localization.", "subcellular localization. only", "localization. only conventional", "only conventional paks", "conventional paks will", "paks will be", "will be annotated", "be annotated here.", "the paks p21", "paks p21 activated", "activated kinases are", "kinases are a", "are a family of", "a family of serine/threonine", "family of serine/threonine kinases", "of serine/threonine kinases mainly", "serine/threonine kinases mainly implicated", "kinases mainly implicated in", "mainly implicated in cytoskeletal", "implicated in cytoskeletal rearrangements.", "in cytoskeletal rearrangements. all", "cytoskeletal rearrangements. all paks", "rearrangements. all paks share", "all paks share a", "paks share a conserved", "share a conserved catalytic", "a conserved catalytic domain", "conserved catalytic domain located", "catalytic domain located at", "domain located at the", "located at the carboxyl", "at the carboxyl terminus", "the carboxyl terminus and", "carboxyl terminus and a", "terminus and a highly", "and a highly conserved", "a highly conserved motif", "highly conserved motif in", "conserved motif in the", "motif in the amino", "in the amino terminus", "the amino terminus known", "amino terminus known as", "terminus known as p21", "known as p21 binding", "as p21 binding domain", "binding domain pbd", "pbd or cdc42/rac", "or cdc42/rac interactive binding", "interactive binding crib", "crib domain. there", "domain. there are six", "there are six mammalian", "are six mammalian paks", "six mammalian paks that", "mammalian paks that can", "paks that can be", "that can be divided", "can be divided into", "be divided into two", "divided into two classes:", "into two classes: class", "two classes: class i", "class i or", "i or conventional", "or conventional paks", "paks pak1 3", "pak1 3 and", "3 and class", "and class ii paks", "ii paks pak4", "paks pak4 6", "pak4 6 . conventional", "6 . conventional paks", ". conventional paks are", "conventional paks are important", "paks are important regulators", "are important regulators of", "important regulators of cytoskeletal", "regulators of cytoskeletal dynamics", "of cytoskeletal dynamics and", "cytoskeletal dynamics and cell", "dynamics and cell motility", "and cell motility and", "cell motility and are", "motility and are additionally", "and are additionally implicated", "are additionally implicated in", "additionally implicated in transcription", "implicated in transcription through", "in transcription through mapk", "through mapk mitogen", "mapk mitogen activated", "mitogen activated protein kinase", "protein kinase cascades", "cascades death and", "death and survival signaling", "and survival signaling and", "survival signaling and cell", "signaling and cell cycle", "and cell cycle progression", "cycle progression chan", "progression chan and", "chan and manser 2012", "and manser 2012 .

pak1", "2012 .

pak1 pak2", ".

pak1 pak2 and", "pak2 and pak3 are", "and pak3 are direct", "pak3 are direct effectors", "are direct effectors of", "direct effectors of rac1", "effectors of rac1 and", "of rac1 and cdc42", "rac1 and cdc42 gtpases.", "and cdc42 gtpases. rac1", "cdc42 gtpases. rac1 and", "gtpases. rac1 and cdc42", "rac1 and cdc42 bind", "and cdc42 bind to", "cdc42 bind to the", "bind to the crib", "to the crib domain.", "the crib domain. this", "crib domain. this binding", "domain. this binding induces", "this binding induces a", "binding induces a conformational", "induces a conformational change", "a conformational change that", "conformational change that disrupts", "change that disrupts inactive", "that disrupts inactive pak", "disrupts inactive pak homodimers", "inactive pak homodimers and", "pak homodimers and relieves", "homodimers and relieves autoinhibition", "and relieves autoinhibition of", "relieves autoinhibition of the", "autoinhibition of the catalytic", "of the catalytic carboxyl", "the catalytic carboxyl terminal", "catalytic carboxyl terminal domain", "terminal domain manser", "domain manser et", "manser et al. 1994", "al. 1994 manser", "1994 manser et", "manser et al. 1995", "al. 1995 zhang", "1995 zhang et", "zhang et al. 1998", "al. 1998 lei", "1998 lei et", "lei et al. 2000", "al. 2000 parrini", "2000 parrini et", "parrini et al. 2002", "al. 2002 reviewed", "2002 reviewed by", "reviewed by daniels and", "by daniels and bokoch", "daniels and bokoch 1999", "bokoch 1999 szczepanowska", "1999 szczepanowska 2009", "szczepanowska 2009 . autophosphorylation", "2009 . autophosphorylation of", ". autophosphorylation of a", "autophosphorylation of a conserved", "of a conserved threonine", "a conserved threonine residue", "conserved threonine residue in", "threonine residue in the", "residue in the catalytic", "in the catalytic domain", "the catalytic domain of", "catalytic domain of paks", "of paks t423", "paks t423 in", "in pak1 t402", "pak1 t402 in", "t402 in pak2 and", "in pak2 and t436", "pak2 and t436 in", "and t436 in pak3", "in pak3 is", "pak3 is necessary", "is necessary for the", "necessary for the kinase", "for the kinase activity", "the kinase activity of", "kinase activity of pak1", "of pak1 pak2", "pak1 pak2 and", "pak2 and pak3. autophosphorylation", "and pak3. autophosphorylation of", "pak3. autophosphorylation of pak1", "autophosphorylation of pak1 serine", "of pak1 serine residue", "pak1 serine residue s144", "residue s144 pak2", "s144 pak2 serine", "pak2 serine residue s141", "residue s141 and", "s141 and pak3", "and pak3 serine residue", "pak3 serine residue s154", "serine residue s154 disrupts", "residue s154 disrupts association", "s154 disrupts association of", "disrupts association of paks", "association of paks with", "of paks with rac1", "paks with rac1 or", "with rac1 or cdc42", "rac1 or cdc42 and", "or cdc42 and enhances", "cdc42 and enhances kinase", "and enhances kinase activity", "kinase activity lei", "activity lei et", "al. 2000 chong", "2000 chong et", "chong et al. 2001", "al. 2001 parrini", "2001 parrini et", "al. 2002 jung", "2002 jung and", "jung and traugh 2005", "traugh 2005 wang", "2005 wang et", "wang et al. 2011", "et al. 2011 .", "al. 2011 . limk1", "2011 . limk1 is", ". limk1 is one", "limk1 is one of", "is one of the", "one of the downstream", "of the downstream targets", "the downstream targets of", "downstream targets of pak1", "targets of pak1 and", "of pak1 and is", "pak1 and is activated", "and is activated through", "is activated through pak1", "activated through pak1 mediated", "through pak1 mediated phosphorylation", "pak1 mediated phosphorylation of", "mediated phosphorylation of the", "phosphorylation of the threonine", "of the threonine residue", "the threonine residue t508", "threonine residue t508 within", "residue t508 within its", "t508 within its activation", "within its activation loop", "activation loop edwards", "loop edwards et", "edwards et al. 1999", "et al. 1999 .", "al. 1999 . further", "1999 . further targets", ". further targets are", "further targets are the", "targets are the myosin", "are the myosin regulatory", "the myosin regulatory light", "myosin regulatory light chain", "light chain mrlc", "mrlc myosin", "myosin light chain kinase", "chain kinase mlck", "mlck filamin", "p41arc a subunit", "a subunit of the", "subunit of the arp2/3", "of the arp2/3 complex", "complex caldesmon", "caldesmon paxillin and", "and rhogdi to", "rhogdi to mention", "to mention a few", "a few szczepanowska", "few szczepanowska 2009", "szczepanowska 2009 .

class ii", "2009 .

class ii paks", ".

class ii paks also", "ii paks also have", "paks also have a", "also have a crib", "have a crib domain", "crib domain but", "domain but lack", "but lack a defined", "lack a defined autoinhibitory", "a defined autoinhibitory domain", "defined autoinhibitory domain and", "autoinhibitory domain and proline", "domain and proline rich", "and proline rich regions.", "proline rich regions. they", "rich regions. they do", "regions. they do not", "they do not require", "do not require gtpases", "not require gtpases for", "require gtpases for their", "gtpases for their kinase", "for their kinase activity", "kinase activity but", "activity but their", "but their interaction with", "their interaction with rac", "interaction with rac or", "with rac or cdc42", "rac or cdc42 affects", "or cdc42 affects their", "cdc42 affects their subcellular", "affects their subcellular localization.", "their subcellular localization. only", "subcellular localization. only conventional", "localization. only conventional paks", "only conventional paks will", "conventional paks will be", "paks will be annotated", "will be annotated here.", "the paks p21 activated", "paks p21 activated kinases", "p21 activated kinases are", "activated kinases are a", "kinases are a family", "are a family of serine/threonine", "a family of serine/threonine kinases", "family of serine/threonine kinases mainly", "of serine/threonine kinases mainly implicated", "serine/threonine kinases mainly implicated in", "kinases mainly implicated in cytoskeletal", "mainly implicated in cytoskeletal rearrangements.", "implicated in cytoskeletal rearrangements. all", "in cytoskeletal rearrangements. all paks", "cytoskeletal rearrangements. all paks share", "rearrangements. all paks share a", "all paks share a conserved", "paks share a conserved catalytic", "share a conserved catalytic domain", "a conserved catalytic domain located", "conserved catalytic domain located at", "catalytic domain located at the", "domain located at the carboxyl", "located at the carboxyl terminus", "at the carboxyl terminus and", "the carboxyl terminus and a", "carboxyl terminus and a highly", "terminus and a highly conserved", "and a highly conserved motif", "a highly conserved motif in", "highly conserved motif in the", "conserved motif in the amino", "motif in the amino terminus", "in the amino terminus known", "the amino terminus known as", "amino terminus known as p21", "terminus known as p21 binding", "known as p21 binding domain", "p21 binding domain pbd", "domain pbd or", "pbd or cdc42/rac interactive", "cdc42/rac interactive binding crib", "binding crib domain.", "crib domain. there are", "domain. there are six mammalian", "there are six mammalian paks", "are six mammalian paks that", "six mammalian paks that can", "mammalian paks that can be", "paks that can be divided", "that can be divided into", "can be divided into two", "be divided into two classes:", "divided into two classes: class", "into two classes: class i", "classes: class i or", "class i or conventional", "conventional paks pak1", "pak1 3 and class", "3 and class ii", "class ii paks pak4", "ii paks pak4 6", "paks pak4 6 .", "pak4 6 . conventional paks", "6 . conventional paks are", ". conventional paks are important", "conventional paks are important regulators", "paks are important regulators of", "are important regulators of cytoskeletal", "important regulators of cytoskeletal dynamics", "regulators of cytoskeletal dynamics and", "of cytoskeletal dynamics and cell", "cytoskeletal dynamics and cell motility", "dynamics and cell motility and", "and cell motility and are", "cell motility and are additionally", "motility and are additionally implicated", "and are additionally implicated in", "are additionally implicated in transcription", "additionally implicated in transcription through", "implicated in transcription through mapk", "transcription through mapk mitogen", "through mapk mitogen activated", "mapk mitogen activated protein", "activated protein kinase cascades", "kinase cascades death", "cascades death and survival", "death and survival signaling and", "and survival signaling and cell", "survival signaling and cell cycle", "signaling and cell cycle progression", "cell cycle progression chan", "cycle progression chan and", "progression chan and manser", "chan and manser 2012 .

pak1", "manser 2012 .

pak1 pak2", "2012 .

pak1 pak2 and", ".

pak1 pak2 and pak3", "pak2 and pak3 are direct", "and pak3 are direct effectors", "pak3 are direct effectors of", "are direct effectors of rac1", "direct effectors of rac1 and", "effectors of rac1 and cdc42", "of rac1 and cdc42 gtpases.", "rac1 and cdc42 gtpases. rac1", "and cdc42 gtpases. rac1 and", "cdc42 gtpases. rac1 and cdc42", "gtpases. rac1 and cdc42 bind", "rac1 and cdc42 bind to", "and cdc42 bind to the", "cdc42 bind to the crib", "bind to the crib domain.", "to the crib domain. this", "the crib domain. this binding", "crib domain. this binding induces", "domain. this binding induces a", "this binding induces a conformational", "binding induces a conformational change", "induces a conformational change that", "a conformational change that disrupts", "conformational change that disrupts inactive", "change that disrupts inactive pak", "that disrupts inactive pak homodimers", "disrupts inactive pak homodimers and", "inactive pak homodimers and relieves", "pak homodimers and relieves autoinhibition", "homodimers and relieves autoinhibition of", "and relieves autoinhibition of the", "relieves autoinhibition of the catalytic", "autoinhibition of the catalytic carboxyl", "of the catalytic carboxyl terminal", "the catalytic carboxyl terminal domain", "carboxyl terminal domain manser", "terminal domain manser et", "domain manser et al.", "et al. 1994 manser", "al. 1994 manser et", "1994 manser et al.", "et al. 1995 zhang", "al. 1995 zhang et", "1995 zhang et al.", "et al. 1998 lei", "al. 1998 lei et", "1998 lei et al.", "et al. 2000 parrini", "al. 2000 parrini et", "2000 parrini et al.", "et al. 2002 reviewed", "al. 2002 reviewed by", "2002 reviewed by daniels", "reviewed by daniels and bokoch", "by daniels and bokoch 1999", "and bokoch 1999 szczepanowska", "bokoch 1999 szczepanowska 2009", "1999 szczepanowska 2009 .", "szczepanowska 2009 . autophosphorylation of", "2009 . autophosphorylation of a", ". autophosphorylation of a conserved", "autophosphorylation of a conserved threonine", "of a conserved threonine residue", "a conserved threonine residue in", "conserved threonine residue in the", "threonine residue in the catalytic", "residue in the catalytic domain", "in the catalytic domain of", "the catalytic domain of paks", "domain of paks t423", "of paks t423 in", "paks t423 in pak1", "t423 in pak1 t402", "in pak1 t402 in", "pak1 t402 in pak2", "t402 in pak2 and t436", "in pak2 and t436 in", "pak2 and t436 in pak3", "t436 in pak3 is", "in pak3 is necessary", "pak3 is necessary for", "is necessary for the kinase", "necessary for the kinase activity", "for the kinase activity of", "the kinase activity of pak1", "activity of pak1 pak2", "of pak1 pak2 and", "pak1 pak2 and pak3.", "pak2 and pak3. autophosphorylation of", "and pak3. autophosphorylation of pak1", "pak3. autophosphorylation of pak1 serine", "autophosphorylation of pak1 serine residue", "of pak1 serine residue s144", "serine residue s144 pak2", "residue s144 pak2 serine", "s144 pak2 serine residue", "serine residue s141 and", "residue s141 and pak3", "s141 and pak3 serine", "and pak3 serine residue s154", "pak3 serine residue s154 disrupts", "serine residue s154 disrupts association", "residue s154 disrupts association of", "s154 disrupts association of paks", "disrupts association of paks with", "association of paks with rac1", "of paks with rac1 or", "paks with rac1 or cdc42", "with rac1 or cdc42 and", "rac1 or cdc42 and enhances", "or cdc42 and enhances kinase", "cdc42 and enhances kinase activity", "enhances kinase activity lei", "kinase activity lei et", "activity lei et al.", "et al. 2000 chong", "al. 2000 chong et", "2000 chong et al.", "et al. 2001 parrini", "al. 2001 parrini et", "2001 parrini et al.", "et al. 2002 jung", "al. 2002 jung and", "2002 jung and traugh", "and traugh 2005 wang", "traugh 2005 wang et", "2005 wang et al.", "wang et al. 2011 .", "et al. 2011 . limk1", "al. 2011 . limk1 is", "2011 . limk1 is one", ". limk1 is one of", "limk1 is one of the", "is one of the downstream", "one of the downstream targets", "of the downstream targets of", "the downstream targets of pak1", "downstream targets of pak1 and", "targets of pak1 and is", "of pak1 and is activated", "pak1 and is activated through", "and is activated through pak1", "is activated through pak1 mediated", "activated through pak1 mediated phosphorylation", "through pak1 mediated phosphorylation of", "pak1 mediated phosphorylation of the", "mediated phosphorylation of the threonine", "phosphorylation of the threonine residue", "of the threonine residue t508", "the threonine residue t508 within", "threonine residue t508 within its", "residue t508 within its activation", "t508 within its activation loop", "its activation loop edwards", "activation loop edwards et", "loop edwards et al.", "edwards et al. 1999 .", "et al. 1999 . further", "al. 1999 . further targets", "1999 . further targets are", ". further targets are the", "further targets are the myosin", "targets are the myosin regulatory", "are the myosin regulatory light", "the myosin regulatory light chain", "regulatory light chain mrlc", "mrlc myosin light", "light chain kinase mlck", "filamin cortactin p41arc", "cortactin p41arc a", "p41arc a subunit of", "a subunit of the arp2/3", "subunit of the arp2/3 complex", "arp2/3 complex caldesmon", "caldesmon paxillin and rhogdi", "paxillin and rhogdi to", "and rhogdi to mention", "rhogdi to mention a", "mention a few szczepanowska", "a few szczepanowska 2009", "few szczepanowska 2009 .

class", "szczepanowska 2009 .

class ii paks", "2009 .

class ii paks also", ".

class ii paks also have", "ii paks also have a", "paks also have a crib", "also have a crib domain", "a crib domain but", "crib domain but lack", "domain but lack a", "but lack a defined autoinhibitory", "lack a defined autoinhibitory domain", "a defined autoinhibitory domain and", "defined autoinhibitory domain and proline", "autoinhibitory domain and proline rich", "domain and proline rich regions.", "and proline rich regions. they", "proline rich regions. they do", "rich regions. they do not", "regions. they do not require", "they do not require gtpases", "do not require gtpases for", "not require gtpases for their", "require gtpases for their kinase", "gtpases for their kinase activity", "their kinase activity but", "kinase activity but their", "activity but their interaction", "but their interaction with rac", "their interaction with rac or", "interaction with rac or cdc42", "with rac or cdc42 affects", "rac or cdc42 affects their", "or cdc42 affects their subcellular", "cdc42 affects their subcellular localization.", "affects their subcellular localization. only", "their subcellular localization. only conventional", "subcellular localization. only conventional paks", "localization. only conventional paks will", "only conventional paks will be", "conventional paks will be annotated", "paks will be annotated here." ] }, { "record_id": "GLY_000594_1_468", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5628897", "r hsa", "hsa 5628897", "r hsa 5628897" ] }, { "record_id": "GLY_000594_1_468", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tp53 regulates", "regulates metabolic", "metabolic genes", "tp53 regulates metabolic", "regulates metabolic genes", "tp53 regulates metabolic genes", "while the", "the p53", "p53 tumor", "tumor suppressor", "suppressor protein", "is known", "known to", "to inhibit", "inhibit cell", "cell growth", "growth by", "by inducing", "inducing apoptosis", "senescence and", "and cell", "cell cycle", "cycle arrest", "recent studies", "studies have", "have found", "found that", "that p53", "p53 is", "is also", "also able", "able to", "to influence", "influence cell", "cell metabolism", "metabolism to", "to prevent", "prevent tumor", "tumor development.", "development. tp53", "regulates transcription", "transcription of", "of many", "many genes", "genes involved", "involved in", "in the", "the metabolism", "metabolism of", "of carbohydrates", "nucleotides and", "and amino", "amino acids", "protein synthesis", "synthesis and", "and aerobic", "aerobic respiration.

tp53", "respiration.

tp53 stimulates", "stimulates transcription", "of tigar", "a d", "d fructose", "fructose 2", "2 6", "6 bisphosphatase.", "bisphosphatase. tigar", "tigar activity", "activity decreases", "decreases glycolytic", "glycolytic rate", "rate and", "and lowers", "lowers ros", "reactive oxygen", "oxygen species", "levels in", "in cells", "bensaad et", "et al.", "al. 2006", "2006 .", ". tp53", "tp53 may", "may also", "also negatively", "negatively regulate", "regulate the", "the rate", "rate of", "of glycolysis", "glycolysis by", "by inhibiting", "inhibiting the", "the expression", "expression of", "of glucose", "glucose transporters", "transporters glut1", "glut3 and", "and glut4", "kondoh et", "al. 2005", "schwartzenberg bar", "bar yoseph", "yoseph et", "al. 2004", "kawauchi et", "al. 2008", "2008 .

tp53", ".

tp53 negatively", "negatively regulates", "regulates several", "several key", "key points", "points in", "in pi3k/akt", "pi3k/akt signaling", "signaling and", "and downstream", "downstream mtor", "mtor signaling", "decreasing the", "of protein", "cellular growth.", "growth. tp53", "tp53 directly", "directly stimulates", "of the", "the tumor", "suppressor pten", "which acts", "acts to", "inhibit pi3k", "pi3k mediated", "mediated activation", "activation of", "of akt", "stambolic et", "al. 2001", "2001 .", "tp53 stimulates", "of sestrin", "sestrin genes", "and sesn3", "velasco miguel", "miguel et", "al. 1999", "budanov et", "al. 2002", "brynczka et", "al. 2007", "2007 .", ". one", "one of", "sestrin functions", "functions may", "may be", "be to", "to reduce", "reduce and", "and reactivate", "reactivate overoxidized", "overoxidized peroxiredoxin", "peroxiredoxin prdx1", "thereby reducing", "reducing ros", "ros levels", "papadia et", "essler et", "al. 2009", "2009 .", ". another", "another function", "function of", "of sestrins", "sestrins is", "is to", "to bind", "bind the", "the activated", "activated ampk", "ampk complex", "complex and", "and protect", "protect it", "it from", "from akt", "akt mediated", "mediated inactivation.", "inactivation. by", "by enhancing", "enhancing ampk", "ampk activity", "sestrins negatively", "regulate mtor", "budanov and", "and karin", "karin 2008", "cam et", "al. 2014", "2014 .", ". the", "of ddit4", "another negative", "negative regulator", "regulator of", "of mtor", "is directly", "directly stimulated", "stimulated by", "by tp63", "tp63 and", "and tp53.", "tp53. ddit4", "ddit4 prevents", "prevents akt", "mediated inactivation", "inactivation of", "of tsc1:tsc2", "tsc1:tsc2 complex", "thus inhibiting", "inhibiting mtor", "mtor cascade", "ellisen et", "deyoung et", "2008 .", "also be", "be involved", "directly or", "or indirectly", "in regulation", "regulation of", "of expression", "of other", "other participants", "participants of", "of pi3k/akt/mtor", "pi3k/akt/mtor signaling", "such as", "as pik3ca", "singh et", "tsc2 and", "and ampkb", "feng et", ".

tp53", "

tp53 regulates", "regulates mitochondrial", "mitochondrial metabolism", "metabolism through", "through several", "several routes.", "routes. tp53", "of sco2", "sco2 gene", "which encodes", "encodes a", "a mitochondrial", "mitochondrial cytochrome", "cytochrome c", "c oxidase", "oxidase assembly", "assembly protein", "matoba et", "of rrm2b", "rrm2b gene", "a subunit", "subunit of", "the ribonucleotide", "ribonucleotide reductase", "reductase complex", "responsible for", "for the", "the conversion", "conversion of", "of ribonucleotides", "ribonucleotides to", "to deoxyribonucleotides", "deoxyribonucleotides and", "and essential", "essential for", "the maintenance", "maintenance of", "of mitochondrial", "mitochondrial dna", "dna content", "content in", "the cell", "tanaka et", "al. 2000", "bourdon et", "kulawiec et", "tp53 also", "also transactivates", "transactivates mitochondrial", "mitochondrial transcription", "transcription factor", "factor a", "a nuclear", "nuclear encoded", "encoded gene", "gene important", "important for", "for mitochondrial", "transcription and", "and maintenance", "park et", ". finally", "the mitochondrial", "mitochondrial glutaminase", "glutaminase gls2", "leading to", "to increased", "increased mitochondrial", "mitochondrial respiration", "respiration rate", "and reduced", "reduced ros", "hu et", "al. 2010", "2010 .", ".

the", "

the great", "great majority", "majority of", "of tumor", "tumor cells", "cells generate", "generate energy", "energy through", "through aerobic", "aerobic glycolysis", "rather than", "than the", "the much", "much more", "more efficient", "efficient aerobic", "aerobic mitochondrial", "and this", "this metabolic", "metabolic change", "change is", "known as", "as the", "the warburg", "warburg effect", "warburg 1956", "1956 .", ". since", "since the", "the majority", "cells have", "have impaired", "impaired tp53", "tp53 function", "and tp53", "regulates a", "a number", "number of", "of genes", "in glycolysis", "glycolysis and", "and mitochondrial", "it is", "is likely", "likely that", "that tp53", "tp53 inactivation", "inactivation plays", "plays an", "an important", "important role", "role in", "the metabolic", "metabolic derangement", "derangement of", "of cancer", "cancer cells", "cells such", "effect and", "and the", "the concomitant", "concomitant increased", "increased tumorigenicity", "reviewed by", "by feng", "feng and", "and levine", "levine 2010", ". on", "on the", "the other", "other hand", "some mutations", "mutations of", "of tp53", "tp53 in", "in li", "li fraumeni", "fraumeni syndrome", "syndrome may", "may result", "result in", "the retention", "retention of", "of its", "its wild", "wild type", "type metabolic", "metabolic activities", "activities while", "while losing", "losing cell", "cycle and", "and apoptosis", "apoptosis functions", "wang et", "al. 2013", "2013 .", ". consistent", "consistent with", "with such", "such human", "human data", "of p53", "unlike p53", "p53 null", "null state", "retain the", "the ability", "ability to", "to regulate", "regulate energy", "energy metabolism", "metabolism while", "while being", "being inactive", "inactive in", "in regulating", "regulating its", "its classic", "classic gene", "gene targets", "targets involved", "in cell", "apoptosis and", "and senescence.", "senescence. retention", "of metabolic", "metabolic and", "and antioxidant", "antioxidant functions", "functions of", "p53 protects", "protects p53", "p53 mutant", "mutant mice", "mice from", "from early", "early onset", "onset tumorigenesis", "li et", "al. 2012", "2012 .", "while the p53", "the p53 tumor", "p53 tumor suppressor", "tumor suppressor protein", "protein tp53", "tp53 is", "is known to", "known to inhibit", "to inhibit cell", "inhibit cell growth", "cell growth by", "growth by inducing", "by inducing apoptosis", "apoptosis senescence", "senescence and cell", "and cell cycle", "cell cycle arrest", "arrest recent", "recent studies have", "studies have found", "have found that", "found that p53", "that p53 is", "p53 is also", "is also able", "also able to", "able to influence", "to influence cell", "influence cell metabolism", "cell metabolism to", "metabolism to prevent", "to prevent tumor", "prevent tumor development.", "tumor development. tp53", "development. tp53 regulates", "tp53 regulates transcription", "regulates transcription of", "transcription of many", "of many genes", "many genes involved", "genes involved in", "involved in the", "in the metabolism", "the metabolism of", "metabolism of carbohydrates", "carbohydrates nucleotides", "nucleotides and amino", "and amino acids", "acids protein", "protein synthesis and", "synthesis and aerobic", "and aerobic respiration.

tp53", "aerobic respiration.

tp53 stimulates", "respiration.

tp53 stimulates transcription", "stimulates transcription of", "transcription of tigar", "tigar a", "a d fructose", "d fructose 2", "fructose 2 6", "2 6 bisphosphatase.", "6 bisphosphatase. tigar", "bisphosphatase. tigar activity", "tigar activity decreases", "activity decreases glycolytic", "decreases glycolytic rate", "glycolytic rate and", "rate and lowers", "and lowers ros", "ros reactive", "reactive oxygen species", "species levels", "levels in cells", "cells bensaad", "bensaad et al.", "et al. 2006", "al. 2006 .", "2006 . tp53", ". tp53 may", "tp53 may also", "may also negatively", "also negatively regulate", "negatively regulate the", "regulate the rate", "the rate of", "rate of glycolysis", "of glycolysis by", "glycolysis by inhibiting", "by inhibiting the", "inhibiting the expression", "the expression of", "expression of glucose", "of glucose transporters", "glucose transporters glut1", "glut1 glut3", "glut3 and glut4", "glut4 kondoh", "kondoh et al.", "et al. 2005", "2005 schwartzenberg", "schwartzenberg bar yoseph", "bar yoseph et", "yoseph et al.", "et al. 2004", "2004 kawauchi", "kawauchi et al.", "et al. 2008", "al. 2008 .

tp53", "2008 .

tp53 negatively", ".

tp53 negatively regulates", "negatively regulates several", "regulates several key", "several key points", "key points in", "points in pi3k/akt", "in pi3k/akt signaling", "pi3k/akt signaling and", "signaling and downstream", "and downstream mtor", "downstream mtor signaling", "signaling decreasing", "decreasing the rate", "rate of protein", "of protein synthesis", "and hence", "hence cellular", "cellular growth. tp53", "growth. tp53 directly", "tp53 directly stimulates", "directly stimulates transcription", "transcription of the", "of the tumor", "the tumor suppressor", "tumor suppressor pten", "pten which", "which acts to", "acts to inhibit", "to inhibit pi3k", "inhibit pi3k mediated", "pi3k mediated activation", "mediated activation of", "activation of akt", "akt stambolic", "stambolic et al.", "et al. 2001", "al. 2001 .", "2001 . tp53", ". tp53 stimulates", "tp53 stimulates transcription", "transcription of sestrin", "of sestrin genes", "genes sesn1", "sesn1 sesn2", "sesn2 and", "sesn3 velasco", "velasco miguel et", "miguel et al.", "et al. 1999", "1999 budanov", "budanov et al.", "et al. 2002", "2002 brynczka", "brynczka et al.", "et al. 2007", "al. 2007 .", "2007 . one", ". one of", "one of sestrin", "of sestrin functions", "sestrin functions may", "functions may be", "may be to", "be to reduce", "to reduce and", "reduce and reactivate", "and reactivate overoxidized", "reactivate overoxidized peroxiredoxin", "overoxidized peroxiredoxin prdx1", "prdx1 thereby", "thereby reducing ros", "reducing ros levels", "levels budanov", "2004 papadia", "papadia et al.", "2008 essler", "essler et al.", "et al. 2009", "al. 2009 .", "2009 . another", ". another function", "another function of", "function of sestrins", "of sestrins is", "sestrins is to", "is to bind", "to bind the", "bind the activated", "the activated ampk", "activated ampk complex", "ampk complex and", "complex and protect", "and protect it", "protect it from", "it from akt", "from akt mediated", "akt mediated inactivation.", "mediated inactivation. by", "inactivation. by enhancing", "by enhancing ampk", "enhancing ampk activity", "activity sestrins", "sestrins negatively regulate", "negatively regulate mtor", "regulate mtor signaling", "signaling budanov", "budanov and karin", "and karin 2008", "2008 cam", "cam et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the expression", "expression of ddit4", "ddit4 redd1", "another negative regulator", "negative regulator of", "regulator of mtor", "of mtor signaling", "signaling is", "is directly stimulated", "directly stimulated by", "stimulated by tp63", "by tp63 and", "tp63 and tp53.", "and tp53. ddit4", "tp53. ddit4 prevents", "ddit4 prevents akt", "prevents akt mediated", "akt mediated inactivation", "mediated inactivation of", "inactivation of tsc1:tsc2", "of tsc1:tsc2 complex", "complex thus", "thus inhibiting mtor", "inhibiting mtor cascade", "cascade cam", "2014 ellisen", "ellisen et al.", "2002 deyoung", "deyoung et al.", "al. 2008 .", "2008 . tp53", "may also be", "also be involved", "involved directly", "directly or indirectly", "indirectly in", "in regulation of", "regulation of expression", "of expression of", "expression of other", "of other participants", "other participants of", "participants of pi3k/akt/mtor", "of pi3k/akt/mtor signaling", "signaling such", "such as pik3ca", "pik3ca singh", "singh et al.", "tsc2 and ampkb", "ampkb feng", "feng et al.", "2007 .

tp53", ".

tp53 regulates", "

tp53 regulates mitochondrial", "regulates mitochondrial metabolism", "mitochondrial metabolism through", "metabolism through several", "through several routes.", "several routes. tp53", "routes. tp53 stimulates", "transcription of sco2", "of sco2 gene", "gene which", "which encodes a", "encodes a mitochondrial", "a mitochondrial cytochrome", "mitochondrial cytochrome c", "cytochrome c oxidase", "c oxidase assembly", "oxidase assembly protein", "protein matoba", "matoba et al.", "transcription of rrm2b", "of rrm2b gene", "encodes a subunit", "a subunit of", "subunit of the", "of the ribonucleotide", "the ribonucleotide reductase", "ribonucleotide reductase complex", "complex responsible", "responsible for the", "for the conversion", "the conversion of", "conversion of ribonucleotides", "of ribonucleotides to", "ribonucleotides to deoxyribonucleotides", "to deoxyribonucleotides and", "deoxyribonucleotides and essential", "and essential for", "essential for the", "for the maintenance", "the maintenance of", "maintenance of mitochondrial", "of mitochondrial dna", "mitochondrial dna content", "dna content in", "content in the", "in the cell", "cell tanaka", "tanaka et al.", "et al. 2000", "2000 bourdon", "bourdon et al.", "2007 kulawiec", "kulawiec et al.", "2009 . tp53", ". tp53 also", "tp53 also transactivates", "also transactivates mitochondrial", "transactivates mitochondrial transcription", "mitochondrial transcription factor", "transcription factor a", "a tfam", "a nuclear encoded", "nuclear encoded gene", "encoded gene important", "gene important for", "important for mitochondrial", "for mitochondrial dna", "dna mtdna", "mtdna transcription", "transcription and maintenance", "maintenance park", "park et al.", "2009 . finally", "finally tp53", "of the mitochondrial", "the mitochondrial glutaminase", "mitochondrial glutaminase gls2", "gls2 leading", "leading to increased", "to increased mitochondrial", "increased mitochondrial respiration", "mitochondrial respiration rate", "respiration rate and", "rate and reduced", "and reduced ros", "reduced ros levels", "levels hu", "hu et al.", "et al. 2010", "al. 2010 .", "2010 .

the", ".

the great", "

the great majority", "great majority of", "majority of tumor", "of tumor cells", "tumor cells generate", "cells generate energy", "generate energy through", "energy through aerobic", "through aerobic glycolysis", "glycolysis rather", "rather than the", "than the much", "the much more", "much more efficient", "more efficient aerobic", "efficient aerobic mitochondrial", "aerobic mitochondrial respiration", "respiration and", "and this metabolic", "this metabolic change", "metabolic change is", "change is known", "is known as", "known as the", "as the warburg", "the warburg effect", "effect warburg", "warburg 1956 .", "1956 . since", ". since the", "since the majority", "the majority of", "tumor cells have", "cells have impaired", "have impaired tp53", "impaired tp53 function", "function and", "and tp53 regulates", "tp53 regulates a", "regulates a number", "a number of", "number of genes", "of genes involved", "involved in glycolysis", "in glycolysis and", "glycolysis and mitochondrial", "and mitochondrial respiration", "respiration it", "it is likely", "is likely that", "likely that tp53", "that tp53 inactivation", "tp53 inactivation plays", "inactivation plays an", "plays an important", "an important role", "important role in", "role in the", "in the metabolic", "the metabolic derangement", "metabolic derangement of", "derangement of cancer", "of cancer cells", "cancer cells such", "cells such as", "such as the", "warburg effect and", "effect and the", "and the concomitant", "the concomitant increased", "concomitant increased tumorigenicity", "tumorigenicity reviewed", "reviewed by feng", "by feng and", "feng and levine", "and levine 2010", "levine 2010 .", "2010 . on", ". on the", "on the other", "the other hand", "hand some", "some mutations of", "mutations of tp53", "of tp53 in", "tp53 in li", "in li fraumeni", "li fraumeni syndrome", "fraumeni syndrome may", "syndrome may result", "may result in", "result in the", "in the retention", "the retention of", "retention of its", "of its wild", "its wild type", "wild type metabolic", "type metabolic activities", "metabolic activities while", "activities while losing", "while losing cell", "losing cell cycle", "cell cycle and", "cycle and apoptosis", "and apoptosis functions", "functions wang", "wang et al.", "et al. 2013", "al. 2013 .", "2013 . consistent", ". consistent with", "consistent with such", "with such human", "such human data", "data some", "mutations of p53", "p53 unlike", "unlike p53 null", "p53 null state", "state retain", "retain the ability", "the ability to", "ability to regulate", "to regulate energy", "regulate energy metabolism", "energy metabolism while", "metabolism while being", "while being inactive", "being inactive in", "inactive in regulating", "in regulating its", "regulating its classic", "its classic gene", "classic gene targets", "gene targets involved", "targets involved in", "involved in cell", "in cell cycle", "cycle apoptosis", "apoptosis and senescence.", "and senescence. retention", "senescence. retention of", "retention of metabolic", "of metabolic and", "metabolic and antioxidant", "and antioxidant functions", "antioxidant functions of", "functions of p53", "of p53 protects", "p53 protects p53", "protects p53 mutant", "p53 mutant mice", "mutant mice from", "mice from early", "from early onset", "early onset tumorigenesis", "tumorigenesis li", "li et al.", "et al. 2012", "al. 2012 .", "while the p53 tumor", "the p53 tumor suppressor", "p53 tumor suppressor protein", "suppressor protein tp53", "tp53 is known", "is known to inhibit", "known to inhibit cell", "to inhibit cell growth", "inhibit cell growth by", "cell growth by inducing", "growth by inducing apoptosis", "inducing apoptosis senescence", "apoptosis senescence and", "senescence and cell cycle", "and cell cycle arrest", "cycle arrest recent", "arrest recent studies", "recent studies have found", "studies have found that", "have found that p53", "found that p53 is", "that p53 is also", "p53 is also able", "is also able to", "also able to influence", "able to influence cell", "to influence cell metabolism", "influence cell metabolism to", "cell metabolism to prevent", "metabolism to prevent tumor", "to prevent tumor development.", "prevent tumor development. tp53", "tumor development. tp53 regulates", "development. tp53 regulates transcription", "tp53 regulates transcription of", "regulates transcription of many", "transcription of many genes", "of many genes involved", "many genes involved in", "genes involved in the", "involved in the metabolism", "in the metabolism of", "the metabolism of carbohydrates", "of carbohydrates nucleotides", "carbohydrates nucleotides and", "nucleotides and amino acids", "amino acids protein", "acids protein synthesis", "protein synthesis and aerobic", "synthesis and aerobic respiration.

tp53", "and aerobic respiration.

tp53 stimulates", "aerobic respiration.

tp53 stimulates transcription", "respiration.

tp53 stimulates transcription of", "stimulates transcription of tigar", "of tigar a", "tigar a d", "a d fructose 2", "d fructose 2 6", "fructose 2 6 bisphosphatase.", "2 6 bisphosphatase. tigar", "6 bisphosphatase. tigar activity", "bisphosphatase. tigar activity decreases", "tigar activity decreases glycolytic", "activity decreases glycolytic rate", "decreases glycolytic rate and", "glycolytic rate and lowers", "rate and lowers ros", "lowers ros reactive", "ros reactive oxygen", "oxygen species levels", "species levels in", "in cells bensaad", "cells bensaad et", "bensaad et al. 2006", "et al. 2006 .", "al. 2006 . tp53", "2006 . tp53 may", ". tp53 may also", "tp53 may also negatively", "may also negatively regulate", "also negatively regulate the", "negatively regulate the rate", "regulate the rate of", "the rate of glycolysis", "rate of glycolysis by", "of glycolysis by inhibiting", "glycolysis by inhibiting the", "by inhibiting the expression", "inhibiting the expression of", "the expression of glucose", "expression of glucose transporters", "of glucose transporters glut1", "transporters glut1 glut3", "glut1 glut3 and", "and glut4 kondoh", "glut4 kondoh et", "kondoh et al. 2005", "al. 2005 schwartzenberg", "2005 schwartzenberg bar", "schwartzenberg bar yoseph et", "bar yoseph et al.", "yoseph et al. 2004", "al. 2004 kawauchi", "2004 kawauchi et", "kawauchi et al. 2008", "et al. 2008 .

tp53", "al. 2008 .

tp53 negatively", "2008 .

tp53 negatively regulates", ".

tp53 negatively regulates several", "negatively regulates several key", "regulates several key points", "several key points in", "key points in pi3k/akt", "points in pi3k/akt signaling", "in pi3k/akt signaling and", "pi3k/akt signaling and downstream", "signaling and downstream mtor", "and downstream mtor signaling", "mtor signaling decreasing", "signaling decreasing the", "decreasing the rate of", "the rate of protein", "rate of protein synthesis", "of protein synthesis and", "synthesis and hence", "hence cellular growth.", "cellular growth. tp53 directly", "growth. tp53 directly stimulates", "tp53 directly stimulates transcription", "directly stimulates transcription of", "stimulates transcription of the", "transcription of the tumor", "of the tumor suppressor", "the tumor suppressor pten", "suppressor pten which", "pten which acts", "which acts to inhibit", "acts to inhibit pi3k", "to inhibit pi3k mediated", "inhibit pi3k mediated activation", "pi3k mediated activation of", "mediated activation of akt", "of akt stambolic", "akt stambolic et", "stambolic et al. 2001", "et al. 2001 .", "al. 2001 . tp53", "2001 . tp53 stimulates", ". tp53 stimulates transcription", "tp53 stimulates transcription of", "stimulates transcription of sestrin", "transcription of sestrin genes", "sestrin genes sesn1", "sesn2 and sesn3", "and sesn3 velasco", "sesn3 velasco miguel", "velasco miguel et al.", "miguel et al. 1999", "al. 1999 budanov", "1999 budanov et", "budanov et al. 2002", "al. 2002 brynczka", "2002 brynczka et", "brynczka et al. 2007", "et al. 2007 .", "al. 2007 . one", "2007 . one of", ". one of sestrin", "one of sestrin functions", "of sestrin functions may", "sestrin functions may be", "functions may be to", "may be to reduce", "be to reduce and", "to reduce and reactivate", "reduce and reactivate overoxidized", "and reactivate overoxidized peroxiredoxin", "reactivate overoxidized peroxiredoxin prdx1", "peroxiredoxin prdx1 thereby", "prdx1 thereby reducing", "thereby reducing ros levels", "ros levels budanov", "levels budanov et", "budanov et al. 2004", "al. 2004 papadia", "2004 papadia et", "papadia et al. 2008", "al. 2008 essler", "2008 essler et", "essler et al. 2009", "et al. 2009 .", "al. 2009 . another", "2009 . another function", ". another function of", "another function of sestrins", "function of sestrins is", "of sestrins is to", "sestrins is to bind", "is to bind the", "to bind the activated", "bind the activated ampk", "the activated ampk complex", "activated ampk complex and", "ampk complex and protect", "complex and protect it", "and protect it from", "protect it from akt", "it from akt mediated", "from akt mediated inactivation.", "akt mediated inactivation. by", "mediated inactivation. by enhancing", "inactivation. by enhancing ampk", "by enhancing ampk activity", "ampk activity sestrins", "activity sestrins negatively", "sestrins negatively regulate mtor", "negatively regulate mtor signaling", "mtor signaling budanov", "signaling budanov and", "budanov and karin 2008", "karin 2008 cam", "2008 cam et", "cam et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the expression", ". the expression of", "the expression of ddit4", "of ddit4 redd1", "redd1 another", "another negative regulator of", "negative regulator of mtor", "regulator of mtor signaling", "mtor signaling is", "signaling is directly", "is directly stimulated by", "directly stimulated by tp63", "stimulated by tp63 and", "by tp63 and tp53.", "tp63 and tp53. ddit4", "and tp53. ddit4 prevents", "tp53. ddit4 prevents akt", "ddit4 prevents akt mediated", "prevents akt mediated inactivation", "akt mediated inactivation of", "mediated inactivation of tsc1:tsc2", "inactivation of tsc1:tsc2 complex", "tsc1:tsc2 complex thus", "complex thus inhibiting", "thus inhibiting mtor cascade", "mtor cascade cam", "cascade cam et", "al. 2014 ellisen", "2014 ellisen et", "ellisen et al. 2002", "al. 2002 deyoung", "2002 deyoung et", "deyoung et al. 2008", "et al. 2008 .", "al. 2008 . tp53", "2008 . tp53 may", "tp53 may also be", "may also be involved", "be involved directly", "involved directly or", "or indirectly in", "indirectly in regulation", "in regulation of expression", "regulation of expression of", "of expression of other", "expression of other participants", "of other participants of", "other participants of pi3k/akt/mtor", "participants of pi3k/akt/mtor signaling", "pi3k/akt/mtor signaling such", "signaling such as", "as pik3ca singh", "pik3ca singh et", "singh et al. 2002", "2002 tsc2", "and ampkb feng", "ampkb feng et", "feng et al. 2007", "al. 2007 .

tp53", "2007 .

tp53 regulates", ".

tp53 regulates mitochondrial", "

tp53 regulates mitochondrial metabolism", "regulates mitochondrial metabolism through", "mitochondrial metabolism through several", "metabolism through several routes.", "through several routes. tp53", "several routes. tp53 stimulates", "routes. tp53 stimulates transcription", "stimulates transcription of sco2", "transcription of sco2 gene", "sco2 gene which", "gene which encodes", "which encodes a mitochondrial", "encodes a mitochondrial cytochrome", "a mitochondrial cytochrome c", "mitochondrial cytochrome c oxidase", "cytochrome c oxidase assembly", "c oxidase assembly protein", "assembly protein matoba", "protein matoba et", "matoba et al. 2006", "2006 . tp53 stimulates", "stimulates transcription of rrm2b", "transcription of rrm2b gene", "rrm2b gene which", "which encodes a subunit", "encodes a subunit of", "a subunit of the", "subunit of the ribonucleotide", "of the ribonucleotide reductase", "the ribonucleotide reductase complex", "reductase complex responsible", "complex responsible for", "responsible for the conversion", "for the conversion of", "the conversion of ribonucleotides", "conversion of ribonucleotides to", "of ribonucleotides to deoxyribonucleotides", "ribonucleotides to deoxyribonucleotides and", "to deoxyribonucleotides and essential", "deoxyribonucleotides and essential for", "and essential for the", "essential for the maintenance", "for the maintenance of", "the maintenance of mitochondrial", "maintenance of mitochondrial dna", "of mitochondrial dna content", "mitochondrial dna content in", "dna content in the", "content in the cell", "the cell tanaka", "cell tanaka et", "tanaka et al. 2000", "al. 2000 bourdon", "2000 bourdon et", "bourdon et al. 2007", "al. 2007 kulawiec", "2007 kulawiec et", "kulawiec et al. 2009", "al. 2009 . tp53", "2009 . tp53 also", ". tp53 also transactivates", "tp53 also transactivates mitochondrial", "also transactivates mitochondrial transcription", "transactivates mitochondrial transcription factor", "mitochondrial transcription factor a", "factor a tfam", "tfam a", "a nuclear encoded gene", "nuclear encoded gene important", "encoded gene important for", "gene important for mitochondrial", "important for mitochondrial dna", "mitochondrial dna mtdna", "mtdna transcription and", "and maintenance park", "maintenance park et", "park et al. 2009", "al. 2009 . finally", ". finally tp53", "finally tp53 stimulates", "transcription of the mitochondrial", "of the mitochondrial glutaminase", "the mitochondrial glutaminase gls2", "glutaminase gls2 leading", "gls2 leading to", "leading to increased mitochondrial", "to increased mitochondrial respiration", "increased mitochondrial respiration rate", "mitochondrial respiration rate and", "respiration rate and reduced", "rate and reduced ros", "and reduced ros levels", "ros levels hu", "levels hu et", "hu et al. 2010", "et al. 2010 .", "al. 2010 .

the", "2010 .

the great", ".

the great majority", "

the great majority of", "great majority of tumor", "majority of tumor cells", "of tumor cells generate", "tumor cells generate energy", "cells generate energy through", "generate energy through aerobic", "energy through aerobic glycolysis", "aerobic glycolysis rather", "glycolysis rather than", "rather than the much", "than the much more", "the much more efficient", "much more efficient aerobic", "more efficient aerobic mitochondrial", "efficient aerobic mitochondrial respiration", "mitochondrial respiration and", "respiration and this", "and this metabolic change", "this metabolic change is", "metabolic change is known", "change is known as", "is known as the", "known as the warburg", "as the warburg effect", "warburg effect warburg", "effect warburg 1956", "warburg 1956 . since", "1956 . since the", ". since the majority", "since the majority of", "the majority of tumor", "of tumor cells have", "tumor cells have impaired", "cells have impaired tp53", "have impaired tp53 function", "tp53 function and", "function and tp53", "and tp53 regulates a", "tp53 regulates a number", "regulates a number of", "a number of genes", "number of genes involved", "of genes involved in", "genes involved in glycolysis", "involved in glycolysis and", "in glycolysis and mitochondrial", "glycolysis and mitochondrial respiration", "mitochondrial respiration it", "respiration it is", "it is likely that", "is likely that tp53", "likely that tp53 inactivation", "that tp53 inactivation plays", "tp53 inactivation plays an", "inactivation plays an important", "plays an important role", "an important role in", "important role in the", "role in the metabolic", "in the metabolic derangement", "the metabolic derangement of", "metabolic derangement of cancer", "derangement of cancer cells", "of cancer cells such", "cancer cells such as", "cells such as the", "such as the warburg", "the warburg effect and", "warburg effect and the", "effect and the concomitant", "and the concomitant increased", "the concomitant increased tumorigenicity", "increased tumorigenicity reviewed", "tumorigenicity reviewed by", "reviewed by feng and", "by feng and levine", "feng and levine 2010", "and levine 2010 .", "levine 2010 . on", "2010 . on the", ". on the other", "on the other hand", "other hand some", "hand some mutations", "some mutations of tp53", "mutations of tp53 in", "of tp53 in li", "tp53 in li fraumeni", "in li fraumeni syndrome", "li fraumeni syndrome may", "fraumeni syndrome may result", "syndrome may result in", "may result in the", "result in the retention", "in the retention of", "the retention of its", "retention of its wild", "of its wild type", "its wild type metabolic", "wild type metabolic activities", "type metabolic activities while", "metabolic activities while losing", "activities while losing cell", "while losing cell cycle", "losing cell cycle and", "cell cycle and apoptosis", "cycle and apoptosis functions", "apoptosis functions wang", "functions wang et", "wang et al. 2013", "et al. 2013 .", "al. 2013 . consistent", "2013 . consistent with", ". consistent with such", "consistent with such human", "with such human data", "human data some", "data some mutations", "some mutations of p53", "of p53 unlike", "p53 unlike p53", "unlike p53 null state", "null state retain", "state retain the", "retain the ability to", "the ability to regulate", "ability to regulate energy", "to regulate energy metabolism", "regulate energy metabolism while", "energy metabolism while being", "metabolism while being inactive", "while being inactive in", "being inactive in regulating", "inactive in regulating its", "in regulating its classic", "regulating its classic gene", "its classic gene targets", "classic gene targets involved", "gene targets involved in", "targets involved in cell", "involved in cell cycle", "cell cycle apoptosis", "cycle apoptosis and", "apoptosis and senescence. retention", "and senescence. retention of", "senescence. retention of metabolic", "retention of metabolic and", "of metabolic and antioxidant", "metabolic and antioxidant functions", "and antioxidant functions of", "antioxidant functions of p53", "functions of p53 protects", "of p53 protects p53", "p53 protects p53 mutant", "protects p53 mutant mice", "p53 mutant mice from", "mutant mice from early", "mice from early onset", "from early onset tumorigenesis", "onset tumorigenesis li", "tumorigenesis li et", "li et al. 2012", "et al. 2012 .", "while the p53 tumor suppressor", "the p53 tumor suppressor protein", "tumor suppressor protein tp53", "protein tp53 is", "tp53 is known to", "is known to inhibit cell", "known to inhibit cell growth", "to inhibit cell growth by", "inhibit cell growth by inducing", "cell growth by inducing apoptosis", "by inducing apoptosis senescence", "inducing apoptosis senescence and", "apoptosis senescence and cell", "senescence and cell cycle arrest", "cell cycle arrest recent", "cycle arrest recent studies", "arrest recent studies have", "recent studies have found that", "studies have found that p53", "have found that p53 is", "found that p53 is also", "that p53 is also able", "p53 is also able to", "is also able to influence", "also able to influence cell", "able to influence cell metabolism", "to influence cell metabolism to", "influence cell metabolism to prevent", "cell metabolism to prevent tumor", "metabolism to prevent tumor development.", "to prevent tumor development. tp53", "prevent tumor development. tp53 regulates", "tumor development. tp53 regulates transcription", "development. tp53 regulates transcription of", "tp53 regulates transcription of many", "regulates transcription of many genes", "transcription of many genes involved", "of many genes involved in", "many genes involved in the", "genes involved in the metabolism", "involved in the metabolism of", "in the metabolism of carbohydrates", "metabolism of carbohydrates nucleotides", "of carbohydrates nucleotides and", "carbohydrates nucleotides and amino", "and amino acids protein", "amino acids protein synthesis", "acids protein synthesis and", "protein synthesis and aerobic respiration.

tp53", "synthesis and aerobic respiration.

tp53 stimulates", "and aerobic respiration.

tp53 stimulates transcription", "aerobic respiration.

tp53 stimulates transcription of", "respiration.

tp53 stimulates transcription of tigar", "transcription of tigar a", "of tigar a d", "tigar a d fructose", "a d fructose 2 6", "d fructose 2 6 bisphosphatase.", "fructose 2 6 bisphosphatase. tigar", "2 6 bisphosphatase. tigar activity", "6 bisphosphatase. tigar activity decreases", "bisphosphatase. tigar activity decreases glycolytic", "tigar activity decreases glycolytic rate", "activity decreases glycolytic rate and", "decreases glycolytic rate and lowers", "glycolytic rate and lowers ros", "and lowers ros reactive", "lowers ros reactive oxygen", "ros reactive oxygen species", "reactive oxygen species levels", "oxygen species levels in", "species levels in cells", "levels in cells bensaad", "in cells bensaad et", "cells bensaad et al.", "bensaad et al. 2006 .", "et al. 2006 . tp53", "al. 2006 . tp53 may", "2006 . tp53 may also", ". tp53 may also negatively", "tp53 may also negatively regulate", "may also negatively regulate the", "also negatively regulate the rate", "negatively regulate the rate of", "regulate the rate of glycolysis", "the rate of glycolysis by", "rate of glycolysis by inhibiting", "of glycolysis by inhibiting the", "glycolysis by inhibiting the expression", "by inhibiting the expression of", "inhibiting the expression of glucose", "the expression of glucose transporters", "expression of glucose transporters glut1", "glucose transporters glut1 glut3", "transporters glut1 glut3 and", "glut1 glut3 and glut4", "glut3 and glut4 kondoh", "and glut4 kondoh et", "glut4 kondoh et al.", "et al. 2005 schwartzenberg", "al. 2005 schwartzenberg bar", "2005 schwartzenberg bar yoseph", "schwartzenberg bar yoseph et al.", "bar yoseph et al. 2004", "et al. 2004 kawauchi", "al. 2004 kawauchi et", "2004 kawauchi et al.", "kawauchi et al. 2008 .

tp53", "et al. 2008 .

tp53 negatively", "al. 2008 .

tp53 negatively regulates", "2008 .

tp53 negatively regulates several", ".

tp53 negatively regulates several key", "negatively regulates several key points", "regulates several key points in", "several key points in pi3k/akt", "key points in pi3k/akt signaling", "points in pi3k/akt signaling and", "in pi3k/akt signaling and downstream", "pi3k/akt signaling and downstream mtor", "signaling and downstream mtor signaling", "downstream mtor signaling decreasing", "mtor signaling decreasing the", "signaling decreasing the rate", "decreasing the rate of protein", "the rate of protein synthesis", "rate of protein synthesis and", "protein synthesis and hence", "and hence cellular", "hence cellular growth. tp53", "cellular growth. tp53 directly stimulates", "growth. tp53 directly stimulates transcription", "tp53 directly stimulates transcription of", "directly stimulates transcription of the", "stimulates transcription of the tumor", "transcription of the tumor suppressor", "of the tumor suppressor pten", "tumor suppressor pten which", "suppressor pten which acts", "pten which acts to", "which acts to inhibit pi3k", "acts to inhibit pi3k mediated", "to inhibit pi3k mediated activation", "inhibit pi3k mediated activation of", "pi3k mediated activation of akt", "activation of akt stambolic", "of akt stambolic et", "akt stambolic et al.", "stambolic et al. 2001 .", "et al. 2001 . tp53", "al. 2001 . tp53 stimulates", "2001 . tp53 stimulates transcription", ". tp53 stimulates transcription of", "tp53 stimulates transcription of sestrin", "stimulates transcription of sestrin genes", "of sestrin genes sesn1", "genes sesn1 sesn2", "sesn1 sesn2 and", "and sesn3 velasco miguel", "sesn3 velasco miguel et", "velasco miguel et al. 1999", "et al. 1999 budanov", "al. 1999 budanov et", "1999 budanov et al.", "et al. 2002 brynczka", "al. 2002 brynczka et", "2002 brynczka et al.", "brynczka et al. 2007 .", "et al. 2007 . one", "al. 2007 . one of", "2007 . one of sestrin", ". one of sestrin functions", "one of sestrin functions may", "of sestrin functions may be", "sestrin functions may be to", "functions may be to reduce", "may be to reduce and", "be to reduce and reactivate", "to reduce and reactivate overoxidized", "reduce and reactivate overoxidized peroxiredoxin", "and reactivate overoxidized peroxiredoxin prdx1", "overoxidized peroxiredoxin prdx1 thereby", "peroxiredoxin prdx1 thereby reducing", "prdx1 thereby reducing ros", "reducing ros levels budanov", "ros levels budanov et", "levels budanov et al.", "et al. 2004 papadia", "al. 2004 papadia et", "2004 papadia et al.", "et al. 2008 essler", "al. 2008 essler et", "2008 essler et al.", "essler et al. 2009 .", "et al. 2009 . another", "al. 2009 . another function", "2009 . another function of", ". another function of sestrins", "another function of sestrins is", "function of sestrins is to", "of sestrins is to bind", "sestrins is to bind the", "is to bind the activated", "to bind the activated ampk", "bind the activated ampk complex", "the activated ampk complex and", "activated ampk complex and protect", "ampk complex and protect it", "complex and protect it from", "and protect it from akt", "protect it from akt mediated", "it from akt mediated inactivation.", "from akt mediated inactivation. by", "akt mediated inactivation. by enhancing", "mediated inactivation. by enhancing ampk", "inactivation. by enhancing ampk activity", "enhancing ampk activity sestrins", "ampk activity sestrins negatively", "activity sestrins negatively regulate", "sestrins negatively regulate mtor signaling", "regulate mtor signaling budanov", "mtor signaling budanov and", "signaling budanov and karin", "and karin 2008 cam", "karin 2008 cam et", "2008 cam et al.", "cam et al. 2014 .", "et al. 2014 . the", "al. 2014 . the expression", "2014 . the expression of", ". the expression of ddit4", "expression of ddit4 redd1", "redd1 another negative", "another negative regulator of mtor", "negative regulator of mtor signaling", "of mtor signaling is", "mtor signaling is directly", "signaling is directly stimulated", "is directly stimulated by tp63", "directly stimulated by tp63 and", "stimulated by tp63 and tp53.", "by tp63 and tp53. ddit4", "tp63 and tp53. ddit4 prevents", "and tp53. ddit4 prevents akt", "tp53. ddit4 prevents akt mediated", "ddit4 prevents akt mediated inactivation", "prevents akt mediated inactivation of", "akt mediated inactivation of tsc1:tsc2", "mediated inactivation of tsc1:tsc2 complex", "of tsc1:tsc2 complex thus", "tsc1:tsc2 complex thus inhibiting", "complex thus inhibiting mtor", "inhibiting mtor cascade cam", "mtor cascade cam et", "cascade cam et al.", "et al. 2014 ellisen", "al. 2014 ellisen et", "2014 ellisen et al.", "et al. 2002 deyoung", "al. 2002 deyoung et", "2002 deyoung et al.", "deyoung et al. 2008 .", "et al. 2008 . tp53", "al. 2008 . tp53 may", "2008 . tp53 may also", ". tp53 may also be", "tp53 may also be involved", "also be involved directly", "be involved directly or", "involved directly or indirectly", "directly or indirectly in", "or indirectly in regulation", "indirectly in regulation of", "in regulation of expression of", "regulation of expression of other", "of expression of other participants", "expression of other participants of", "of other participants of pi3k/akt/mtor", "other participants of pi3k/akt/mtor signaling", "of pi3k/akt/mtor signaling such", "pi3k/akt/mtor signaling such as", "signaling such as pik3ca", "such as pik3ca singh", "as pik3ca singh et", "pik3ca singh et al.", "al. 2002 tsc2", "2002 tsc2 and", "tsc2 and ampkb feng", "and ampkb feng et", "ampkb feng et al.", "feng et al. 2007 .", "et al. 2007 .

tp53", "al. 2007 .

tp53 regulates", "2007 .

tp53 regulates mitochondrial", ".

tp53 regulates mitochondrial metabolism", "

tp53 regulates mitochondrial metabolism through", "regulates mitochondrial metabolism through several", "mitochondrial metabolism through several routes.", "metabolism through several routes. tp53", "through several routes. tp53 stimulates", "several routes. tp53 stimulates transcription", "routes. tp53 stimulates transcription of", "tp53 stimulates transcription of sco2", "stimulates transcription of sco2 gene", "of sco2 gene which", "sco2 gene which encodes", "gene which encodes a", "which encodes a mitochondrial cytochrome", "encodes a mitochondrial cytochrome c", "a mitochondrial cytochrome c oxidase", "mitochondrial cytochrome c oxidase assembly", "cytochrome c oxidase assembly protein", "oxidase assembly protein matoba", "assembly protein matoba et", "protein matoba et al.", "matoba et al. 2006 .", "al. 2006 . tp53 stimulates", "2006 . tp53 stimulates transcription", "tp53 stimulates transcription of rrm2b", "stimulates transcription of rrm2b gene", "of rrm2b gene which", "rrm2b gene which encodes", "which encodes a subunit of", "encodes a subunit of the", "a subunit of the ribonucleotide", "subunit of the ribonucleotide reductase", "of the ribonucleotide reductase complex", "ribonucleotide reductase complex responsible", "reductase complex responsible for", "complex responsible for the", "responsible for the conversion of", "for the conversion of ribonucleotides", "the conversion of ribonucleotides to", "conversion of ribonucleotides to deoxyribonucleotides", "of ribonucleotides to deoxyribonucleotides and", "ribonucleotides to deoxyribonucleotides and essential", "to deoxyribonucleotides and essential for", "deoxyribonucleotides and essential for the", "and essential for the maintenance", "essential for the maintenance of", "for the maintenance of mitochondrial", "the maintenance of mitochondrial dna", "maintenance of mitochondrial dna content", "of mitochondrial dna content in", "mitochondrial dna content in the", "dna content in the cell", "in the cell tanaka", "the cell tanaka et", "cell tanaka et al.", "et al. 2000 bourdon", "al. 2000 bourdon et", "2000 bourdon et al.", "et al. 2007 kulawiec", "al. 2007 kulawiec et", "2007 kulawiec et al.", "kulawiec et al. 2009 .", "et al. 2009 . tp53", "al. 2009 . tp53 also", "2009 . tp53 also transactivates", ". tp53 also transactivates mitochondrial", "tp53 also transactivates mitochondrial transcription", "also transactivates mitochondrial transcription factor", "transactivates mitochondrial transcription factor a", "transcription factor a tfam", "tfam a nuclear", "a nuclear encoded gene important", "nuclear encoded gene important for", "encoded gene important for mitochondrial", "gene important for mitochondrial dna", "for mitochondrial dna mtdna", "dna mtdna transcription", "mtdna transcription and maintenance", "transcription and maintenance park", "and maintenance park et", "maintenance park et al.", "park et al. 2009 .", "et al. 2009 . finally", "2009 . finally tp53", ". finally tp53 stimulates", "finally tp53 stimulates transcription", "tp53 stimulates transcription of the", "stimulates transcription of the mitochondrial", "transcription of the mitochondrial glutaminase", "of the mitochondrial glutaminase gls2", "mitochondrial glutaminase gls2 leading", "glutaminase gls2 leading to", "gls2 leading to increased", "leading to increased mitochondrial respiration", "to increased mitochondrial respiration rate", "increased mitochondrial respiration rate and", "mitochondrial respiration rate and reduced", "respiration rate and reduced ros", "rate and reduced ros levels", "reduced ros levels hu", "ros levels hu et", "levels hu et al.", "hu et al. 2010 .", "et al. 2010 .

the", "al. 2010 .

the great", "2010 .

the great majority", ".

the great majority of", "

the great majority of tumor", "great majority of tumor cells", "majority of tumor cells generate", "of tumor cells generate energy", "tumor cells generate energy through", "cells generate energy through aerobic", "generate energy through aerobic glycolysis", "through aerobic glycolysis rather", "aerobic glycolysis rather than", "glycolysis rather than the", "rather than the much more", "than the much more efficient", "the much more efficient aerobic", "much more efficient aerobic mitochondrial", "more efficient aerobic mitochondrial respiration", "aerobic mitochondrial respiration and", "mitochondrial respiration and this", "respiration and this metabolic", "and this metabolic change is", "this metabolic change is known", "metabolic change is known as", "change is known as the", "is known as the warburg", "known as the warburg effect", "the warburg effect warburg", "warburg effect warburg 1956", "effect warburg 1956 .", "warburg 1956 . since the", "1956 . since the majority", ". since the majority of", "since the majority of tumor", "the majority of tumor cells", "majority of tumor cells have", "of tumor cells have impaired", "tumor cells have impaired tp53", "cells have impaired tp53 function", "impaired tp53 function and", "tp53 function and tp53", "function and tp53 regulates", "and tp53 regulates a number", "tp53 regulates a number of", "regulates a number of genes", "a number of genes involved", "number of genes involved in", "of genes involved in glycolysis", "genes involved in glycolysis and", "involved in glycolysis and mitochondrial", "in glycolysis and mitochondrial respiration", "and mitochondrial respiration it", "mitochondrial respiration it is", "respiration it is likely", "it is likely that tp53", "is likely that tp53 inactivation", "likely that tp53 inactivation plays", "that tp53 inactivation plays an", "tp53 inactivation plays an important", "inactivation plays an important role", "plays an important role in", "an important role in the", "important role in the metabolic", "role in the metabolic derangement", "in the metabolic derangement of", "the metabolic derangement of cancer", "metabolic derangement of cancer cells", "derangement of cancer cells such", "of cancer cells such as", "cancer cells such as the", "cells such as the warburg", "such as the warburg effect", "as the warburg effect and", "the warburg effect and the", "warburg effect and the concomitant", "effect and the concomitant increased", "and the concomitant increased tumorigenicity", "concomitant increased tumorigenicity reviewed", "increased tumorigenicity reviewed by", "tumorigenicity reviewed by feng", "reviewed by feng and levine", "by feng and levine 2010", "feng and levine 2010 .", "and levine 2010 . on", "levine 2010 . on the", "2010 . on the other", ". on the other hand", "the other hand some", "other hand some mutations", "hand some mutations of", "some mutations of tp53 in", "mutations of tp53 in li", "of tp53 in li fraumeni", "tp53 in li fraumeni syndrome", "in li fraumeni syndrome may", "li fraumeni syndrome may result", "fraumeni syndrome may result in", "syndrome may result in the", "may result in the retention", "result in the retention of", "in the retention of its", "the retention of its wild", "retention of its wild type", "of its wild type metabolic", "its wild type metabolic activities", "wild type metabolic activities while", "type metabolic activities while losing", "metabolic activities while losing cell", "activities while losing cell cycle", "while losing cell cycle and", "losing cell cycle and apoptosis", "cell cycle and apoptosis functions", "and apoptosis functions wang", "apoptosis functions wang et", "functions wang et al.", "wang et al. 2013 .", "et al. 2013 . consistent", "al. 2013 . consistent with", "2013 . consistent with such", ". consistent with such human", "consistent with such human data", "such human data some", "human data some mutations", "data some mutations of", "mutations of p53 unlike", "of 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functions", "metabolic and antioxidant functions of", "and antioxidant functions of p53", "antioxidant functions of p53 protects", "functions of p53 protects p53", "of p53 protects p53 mutant", "p53 protects p53 mutant mice", "protects p53 mutant mice from", "p53 mutant mice from early", "mutant mice from early onset", "mice from early onset tumorigenesis", "early onset tumorigenesis li", "onset tumorigenesis li et", "tumorigenesis li et al.", "li et al. 2012 ." ] }, { "record_id": "GLY_000594_1_469", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5632684", "r hsa", "hsa 5632684", "r hsa 5632684" ] }, { "record_id": "GLY_000594_1_469", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hedgehog 'on'", "'on' state", "hedgehog 'on' state", "hedgehog is", "is a", "a secreted", "secreted morphogen", "morphogen that", "that has", "has evolutionarily", "evolutionarily conserved", "conserved roles", 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", ".
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while", "
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vertebrate", ".
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of", "number of cilia", "of cilia related", "cilia related proteins", "related proteins that", "proteins that are", "that are required", "are required both", "required both to", "both to maintain", "to maintain hh", "maintain hh in", "hh in the", "in the 'off'", "the 'off' state", "'off' state and", "state and to", "and to transduce", "to transduce the", "transduce the signal", "the signal when", "signal when the", "when the pathway", "the pathway is", "pathway is activated", "activated reviewed", "reviewed in hui", "in hui and", "hui and angers", "angers 2011", "2011 goetz", "goetz and anderson", "anderson 2010", "hedgehog is a secreted", "is a secreted morphogen", "a secreted morphogen that", "secreted morphogen that has", "morphogen that has evolutionarily", "that has evolutionarily conserved", "has evolutionarily conserved roles", "evolutionarily conserved roles in", "conserved roles in body", "roles in body organization", "in body organization by", "body organization by 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to the nucleus", "to the nucleus to", "the nucleus to represses", "nucleus to represses hh", "to represses hh responsive", "represses hh responsive genes.", "hh responsive genes. binding", "responsive genes. binding of", "genes. binding of hh", "binding of hh ligand", "of hh ligand to", "hh ligand to the", "ligand to the patched", "the patched ptc", "ptc receptor allows", "receptor allows the 7", "allows the 7 pass", "the 7 pass transmembrane", "7 pass transmembrane protein", "pass transmembrane protein smoothened", "protein smoothened smo", "smo to be", "to be activated in", "be activated in an", "activated in an unknown", "in an unknown manner", "unknown manner disrupting", "manner disrupting the", "disrupting the partial proteolysis", "the partial proteolysis of", "partial proteolysis of ci", "proteolysis of ci and", "of ci and allowing", "ci and allowing the", "and allowing the full", "allowing the full length", "the full length activator", "full length activator form", "length activator form to", "activator form to accumulate", "to accumulate reviewed", "accumulate reviewed in", "reviewed in ingham et", "in ingham et al", "et al 2011", "2011 briscoe and", "and therond 2013", "therond 2013 .", "2013 .
while", ".
while many", "
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", "2013 .
vertebrate but", ".
vertebrate but not", "vertebrate but not fly", "but not fly hh", "not fly hh signaling", "fly hh signaling also", "hh signaling also depends", "signaling also depends on", "also depends on the", "depends on the movement", "on the movement of", "the movement of pathway", "movement of pathway components", "of pathway components through", "pathway components through the", "components through the primary", "through the primary cilium.", "the primary cilium. the", "primary cilium. the primary", "cilium. the primary cilium", "the primary cilium is", "primary cilium is a", "cilium is a non", "is a non motile", "a non motile microtubule", "non motile microtubule based", "motile microtubule based structure", "microtubule based structure whose", "based structure whose construction", "structure whose construction and", "whose construction and maintenance", "construction and maintenance depends", "and maintenance depends on", "maintenance depends on intraflagellar", "depends on intraflagellar transport", "intraflagellar transport ift", "transport ift .", "ift . anterograde ift", ". anterograde ift moves", "anterograde ift moves molecules", "ift moves molecules from", "moves molecules from the", "molecules from the ciliary", "from the ciliary base", "the ciliary base along", "ciliary base along the", "base along the axoneme", "along the axoneme to", "the axoneme to the", "axoneme to the ciliary", "to the ciliary tip", "the ciliary tip in", "ciliary tip in a", "tip in a manner", "in a manner that", "a manner that requires", "manner that requires the", "that requires the microtubule", "requires the microtubule plus", "the microtubule plus end", "microtubule plus end directed", "plus end directed kinesin", "end directed kinesin kif3", "directed kinesin kif3 motor", "kinesin kif3 motor complex", "kif3 motor complex and", "motor complex and the", "complex and the ift", "and the ift b", "the ift b protein", "ift b protein complex", "protein complex while", "complex while 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'off' state", "the 'off' state and", "'off' state and to", "state and to transduce", "and to transduce the", "to transduce the signal", "transduce the signal when", "the signal when the", "signal when the pathway", "when the pathway is", "the pathway is activated", "is activated reviewed", "activated reviewed in", "reviewed in hui and", "in hui and angers", "and angers 2011", "2011 goetz and", "and anderson 2010", "anderson 2010 .", "hedgehog is a secreted morphogen", "is a secreted morphogen that", "a secreted morphogen that has", "secreted morphogen that has evolutionarily", "morphogen that has evolutionarily conserved", "that has evolutionarily conserved roles", "has evolutionarily conserved roles in", "evolutionarily conserved roles in body", "conserved roles in body organization", "roles in body organization by", "in body organization by regulating", "body organization by regulating the", "organization by regulating the activity", "by regulating the activity of", "regulating the activity of the", "the activity of the ci/gli", "activity of the ci/gli transcription", "of the ci/gli transcription factor", "the ci/gli transcription factor family.", "ci/gli transcription factor family. in", "transcription factor family. in drosophila", "factor family. in drosophila in", "family. in drosophila in the", "in drosophila in the absence", "drosophila in the absence of", "in the absence of hh", "the absence of hh signaling", "of hh signaling full", "hh signaling full length", "signaling full length ci", "full length ci is partially", "length ci is partially degraded", "ci is partially degraded by", "is partially degraded by the", "partially degraded by the proteasome", "degraded by the proteasome to", "by the proteasome to generate", "the proteasome to generate a", "proteasome to generate a truncated", "to generate a truncated repressor", "generate a truncated repressor form", "a truncated repressor form that", "truncated repressor form that translocates", "repressor form that translocates to", "form that translocates to the", "that translocates to the nucleus", "translocates to the nucleus to", "to the nucleus to represses", "the nucleus to represses hh", "nucleus to represses hh responsive", "to represses hh responsive genes.", "represses hh responsive genes. binding", "hh responsive genes. binding of", "responsive genes. binding of hh", "genes. binding of hh ligand", "binding of hh ligand to", "of hh ligand to the", "hh ligand to the patched", "to the patched ptc", "patched ptc receptor", "ptc receptor allows the", "receptor allows the 7 pass", "allows the 7 pass transmembrane", "the 7 pass transmembrane protein", "7 pass transmembrane protein smoothened", "transmembrane protein smoothened smo", "smoothened smo to", "smo to be activated", "to be activated in an", "be activated in an unknown", "activated in an unknown manner", "an unknown manner disrupting", "unknown manner disrupting the", "manner disrupting the partial", "disrupting the partial proteolysis of", "the partial proteolysis of ci", "partial proteolysis of ci and", "proteolysis of ci and allowing", "of ci and allowing the", "ci and allowing the full", "and allowing the full length", "allowing the full length activator", "the full length activator form", "full length activator form to", "length activator form to accumulate", "form to accumulate reviewed", "to accumulate reviewed in", "accumulate reviewed in ingham", "reviewed in ingham et al", "ingham et al 2011", "al 2011 briscoe", "2011 briscoe and therond", "briscoe and therond 2013", "and therond 2013 .", "2013 .
while many", ".
while many of", "
while many of the core", "many of the core components", "of the core components of", "the core components of hh", "core components of hh signaling", "components of hh signaling are", "of hh signaling are conserved", "hh signaling are conserved from", "signaling are conserved from flies", "are conserved from flies to", "conserved from flies to humans", "flies to humans the", "to humans the pathways", "humans the pathways do", "the pathways do show points", "pathways do show points of", "do show points of significant", "show points of significant divergence.", "points of significant divergence. notably", "significant divergence. notably the", "divergence. notably the human", "notably the human genome", "the human genome encodes three", "human genome encodes three ci", "genome encodes three ci homologues", "three ci homologues gli1", "homologues gli1 2", "gli1 2 and 3", "2 and 3 that each", "and 3 that each play", "3 that each play slightly", "that each play slightly different", "each play slightly different roles", "play slightly different roles in", "slightly different roles in regulating", "different roles in regulating hh", "roles in regulating hh responsive", "in regulating hh responsive genes.", "regulating hh responsive genes. gli3", "hh responsive genes. gli3 is", "responsive genes. gli3 is the", "genes. gli3 is the primary", "gli3 is the primary repressor", "is the primary repressor of", "the primary repressor of hh", "primary repressor of hh signaling", "repressor of hh signaling in", "of hh signaling in vertebrates", "signaling in vertebrates and", "in vertebrates and is", "vertebrates and is converted", "and is converted to the", "is converted to the truncated", "converted to the truncated gli3r", "to the truncated gli3r repressor", "the truncated gli3r repressor form", "truncated gli3r repressor form in", "gli3r repressor form in the", "repressor form in the absence", "form in the absence of", "in the absence of hh.", "the absence of hh. gli2", "absence of hh. gli2 is", "of hh. gli2 is a", "hh. gli2 is a potent", "gli2 is a potent activator", "is a potent activator of", "a potent activator of transcription", "potent activator of transcription in", "activator of transcription in the", "of transcription in the presence", "transcription in the presence of", "in the presence of hh", "the presence of hh but", "presence of hh but contributes", "of hh but contributes only", "hh but contributes only minimally", "but contributes only minimally to", "contributes only minimally to the", "only minimally to the repression", "minimally to the repression function.", "to the repression function. while", "the repression function. while a", "repression function. while a minor", "function. while a minor fraction", "while a minor fraction of", "a minor fraction of gli2", "minor fraction of gli2 protein", "fraction of gli2 protein is", "of gli2 protein is processed", "gli2 protein is processed into", "protein is processed into the", "is processed into the repressor", "processed into the repressor form", "into the repressor form in", "the repressor form in the", "absence of hh the", "of hh the majority", "hh the majority is", "the majority is either fully", "majority is either fully degraded", "is either fully degraded by", "either fully degraded by the", "fully degraded by the proteasome", "degraded by the proteasome or", "by the proteasome or sequestered", "the proteasome or sequestered in", "proteasome or sequestered in the", "or sequestered in the full", "sequestered in the full length", "in the full length form", "the full length form in", "full length form in the", "length form in the cytosol", "form in the cytosol by", "in the cytosol by protein", "the cytosol by protein protein", "cytosol by protein protein interactions.", "by protein protein interactions. gli1", "protein protein interactions. gli1 lacks", "protein interactions. gli1 lacks the", "interactions. gli1 lacks the repression", "gli1 lacks the repression domain", "lacks the repression domain and", "the repression domain and appears", "repression domain and appears to", "domain and appears to be", "and appears to be an", "appears to be an obligate", "to be an obligate transcriptional", "be an obligate transcriptional activator", "obligate transcriptional activator reviewed", "transcriptional activator reviewed in", "activator reviewed in briscoe", "reviewed in briscoe and therond", "and therond 2013 .
", "therond 2013 .
vertebrate", "2013 .
vertebrate but not", ".
vertebrate but not fly", "vertebrate but not fly hh", "but not fly hh signaling", "not fly hh signaling also", "fly hh signaling also depends", "hh signaling also depends on", "signaling also depends on the", "also depends on the movement", "depends on the movement of", "on the movement of pathway", "the movement of pathway components", "movement of pathway components through", "of pathway components through the", "pathway components through the primary", "components through the primary cilium.", "through the primary cilium. the", "the primary cilium. the primary", "primary cilium. the primary cilium", "cilium. the primary cilium is", "the primary cilium is a", "primary cilium is a non", "cilium is a non motile", "is a non motile microtubule", "a non motile microtubule based", "non motile microtubule based structure", "motile microtubule based structure whose", "microtubule based structure whose construction", "based structure whose construction and", "structure whose construction and maintenance", "whose construction and maintenance depends", "construction and maintenance depends on", "and maintenance depends on intraflagellar", "maintenance depends on intraflagellar transport", "on intraflagellar transport ift", "intraflagellar transport ift .", "transport ift . anterograde", "ift . anterograde ift moves", ". anterograde ift moves molecules", "anterograde ift moves molecules from", "ift moves molecules from the", "moves molecules from the ciliary", "molecules from the ciliary base", "from the ciliary base along", "the ciliary base along the", "ciliary base along the axoneme", "base along the axoneme to", "along the axoneme to the", "the axoneme to the ciliary", "axoneme to the ciliary tip", "to the ciliary tip in", "the ciliary tip in a", "ciliary tip in a manner", "tip in a manner that", "in a manner that requires", "a manner that requires the", "manner that requires the microtubule", "that requires the microtubule plus", "requires the microtubule plus end", "the microtubule plus end directed", "microtubule plus end directed kinesin", "plus end directed kinesin kif3", "end directed kinesin kif3 motor", "directed kinesin kif3 motor complex", "kinesin kif3 motor complex and", "kif3 motor complex and the", "motor complex and the ift", "complex and the ift b", "and the ift b protein", "the ift b protein complex", "b protein complex while", "protein complex while retrograde", "complex while retrograde ift", "while retrograde ift back to", "retrograde ift back to the", "ift back to the ciliary", "back to the ciliary base", "to the ciliary base depends", "the ciliary base depends on", "ciliary base depends on the", "base depends on the minus", "depends on the minus end", "on the minus end directed", "the minus end directed dynein", "minus end directed dynein motor", "end directed dynein motor and", "directed dynein motor and the", "dynein motor and the ift", "motor and the ift a", "and the ift a complex.", "the ift a complex. genetic", "ift a complex. genetic screens", "a complex. genetic screens have", "complex. genetic screens have identified", "genetic screens have identified a", "screens have identified a number", "have identified a number of", "identified a number of cilia", "a number of cilia related", "number of cilia related proteins", "of cilia related proteins that", "cilia related proteins that are", "related proteins that are required", "proteins that are required both", "that are required both to", "are required both to maintain", "required both to maintain hh", "both to maintain hh in", "to maintain hh in the", "maintain hh in the 'off'", "hh in the 'off' state", "in the 'off' state and", "the 'off' state and to", "'off' state and to transduce", "state and to transduce the", "and to transduce the signal", "to transduce the signal when", "transduce the signal when the", "the signal when the pathway", "signal when the pathway is", "when the pathway is activated", "pathway is activated reviewed", "is activated reviewed in", "activated reviewed in hui", "reviewed in hui and angers", "hui and angers 2011", "angers 2011 goetz", "2011 goetz and anderson", "goetz and anderson 2010", "and anderson 2010 ." ] }, { "record_id": "GLY_000594_1_470", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5635838", "r hsa", "hsa 5635838", "r hsa 5635838" ] }, { "record_id": "GLY_000594_1_470", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of smo", "activation of smo", "of the", "the transmembrane", "transmembrane protein", "protein smo", "smo in", "in response", "response to", "to hh", "hh stimulation", "stimulation is", "is a", "a major", "major control", "control point", "point in", "in the", "the hh", "hh signaling", "signaling pathway", "reviewed in", "in ayers", "ayers and", "and therond", "jiang and", "and hui", "2008 .", ". in", "the absence", "absence of", "of ligand", "smo is", "is inhibited", "inhibited in", "in an", "an unknown", "unknown manner", "manner by", "by the", "hh receptor", "receptor ptch.", "ptch. ptch", "ptch regulates", "regulates smo", "in a", "a non", "non stoichiometric", "stoichiometric manner", "manner and", "and there", "there is", "is little", "little evidence", "evidence that", "that endogenous", "endogenous ptch", "ptch and", "and smo", "smo interact", "interact directly", "taipale et", "et al", "in huangfu", "huangfu and", "and anderson", "2006 .", ". ptch", "ptch may", "may regulate", "regulate smo", "smo activity", "activity by", "by controlling", "controlling the", "the flux", "flux of", "of sterol", "sterol related", "related smo", "smo agonists", "agonists and/or", "and/or antagonists", "although this", "this has", "has not", "not been", "been fully", "fully substantiated", "khaliullina et", "in rohatgi", "rohatgi and", "and scott", "briscoe and", "2013 .

ptch", ".

ptch mediated", "mediated inhibition", "inhibition of", "is relieved", "relieved upon", "upon ligand", "ligand stimulation", "stimulation of", "of ptch", "but the", "the mechanisms", "mechanisms for", "for this", "this relief", "relief are", "are again", "again unknown.", "unknown. smo", "smo and", "and ptch", "ptch appear", "appear to", "to have", "have opposing", "opposing localizations", "localizations in", "in both", "both the", "the 'off'", "'off' and", "and 'on'", "'on' state", "with ptch", "ptch exiting", "exiting and", "smo entering", "entering the", "the cilium", "cilium upon", "upon hh", "hh pathway", "pathway activation", "denef et", "rohatgi et", "in goetz", "goetz and", "hui and", "and angers", "2011 .", ". activation", "smo involves", "involves a", "a conserved", "conserved phosphorylation", "phosphorylation mediated", "mediated conformational", "conformational change", "change in", "the c", "c terminal", "terminal tails", "tails that", "that destabilizes", "destabilizes an", "an intramolecular", "intramolecular interaction", "interaction and", "and promotes", "promotes the", "the interaction", "interaction between", "between adjacent", "adjacent tails", "tails in", "the smo", "smo dimer.", "in drosophila", "this phosphorylation", "phosphorylation is", "is mediated", "mediated by", "by pka", "pka and", "and ck1", "while in", "in vertebrates", "vertebrates it", "it appears", "appears to", "to involve", "involve adrbk1/grk2", "adrbk1/grk2 and", "and csnk1a1.", "csnk1a1. sequential", "sequential phosphorylations", "phosphorylations along", "along multiple", "multiple serine", "serine and", "and threonine", "threonine motifs", "motifs in", "smo c", "terminal tail", "tail appear", "to allow", "allow a", "a graded", "graded response", "hh ligand", "ligand concentration", "concentration in", "both flies", "flies and", "and vertebrates", "zhao et", "chen et", "in flies", "tail phosphorylation", "phosphorylation promotes", "promotes an", "an association", "association with", "with the", "the hedgehog", "hedgehog signaling", "signaling complex", "through interaction", "interaction with", "the scaffolding", "scaffolding kinesin", "kinesin 2", "2 like", "like protein", "protein cos2", "activating the", "the fu", "fu kinase", "kinase and", "and ultimately", "ultimately releasing", "releasing uncleaved", "uncleaved ci", "ci from", "from the", "the complex", "zhang et", "ogden et", "lum et", "in mukhopadhyay", "mukhopadhyay and", "and rohatgi", "2014 .", "phosphorylation and", "and conformational", "change is", "is linked", "linked to", "to its", "its kif7", "kif7 dependent", "dependent ciliary", "ciliary accumulation", "2010 .", "is restricted", "restricted to", "to a", "a transition", "transition zone", "zone proximal", "proximal region", "region known", "known as", "as the", "the evc", "evc zone", "yang et", "blair et", "pusapati et", "in eggenschwiler", "eggenschwiler 2012", "2012 .", ". both", "both smo", "smo phosphorylation", "and its", "its ciliary", "ciliary localization", "localization are", "are required", "required to", "to promote", "promote the", "hh dependent", "dependent dissociation", "dissociation of", "the gli:sufu", "gli:sufu complex", "ultimately allowing", "allowing full", "full length", "length gli", "gli transcription", "transcription factors", "factors to", "to translocate", "translocate to", "to the", "the nucleus", "nucleus to", "to activate", "activate hh", "hh responsive", "responsive genes", "in briscoe", "2013 .


", "activation of the", "of the transmembrane", "the transmembrane protein", "transmembrane protein smo", "protein smo in", "smo in response", "in response to", "response to hh", "to hh stimulation", "hh stimulation is", "stimulation is a", "is a major", "a major control", "major control point", "control point in", "point in the", "in the hh", "the hh signaling", "hh signaling pathway", "pathway reviewed", "reviewed in ayers", "in ayers and", "ayers and therond", "therond 2010", "2010 jiang", "jiang and hui", "hui 2008", "2008 . in", ". in the", "in the absence", "the absence of", "absence of ligand", "ligand smo", "smo is inhibited", "is inhibited in", "inhibited in an", "in an unknown", "an unknown manner", "unknown manner by", "manner by the", "by the hh", "the hh receptor", "hh receptor ptch.", "receptor ptch. ptch", "ptch. ptch regulates", "ptch regulates smo", "regulates smo in", "smo in a", "in a non", "a non stoichiometric", "non stoichiometric manner", "stoichiometric manner and", "manner and there", "and there is", "there is little", "is little evidence", "little evidence that", "evidence that endogenous", "that endogenous ptch", "endogenous ptch and", "ptch and smo", "and smo interact", "smo interact directly", "directly taipale", "taipale et al", "al 2002", "2002 reviewed", "reviewed in huangfu", "in huangfu and", "huangfu and anderson", "anderson 2006", "2006 . ptch", ". ptch may", "ptch may regulate", "may regulate smo", "regulate smo activity", "smo activity by", "activity by controlling", "by controlling the", "controlling the flux", "the flux of", "flux of sterol", "of sterol related", "sterol related smo", "related smo agonists", "smo agonists and/or", "agonists and/or antagonists", "antagonists although", "although this has", "this has not", "has not been", "not been fully", "been fully substantiated", "substantiated khaliullina", "khaliullina et al", "al 2009", "2009 reviewed", "reviewed in rohatgi", "in rohatgi and", "rohatgi and scott", "scott 2007", "2007 briscoe", "briscoe and therond", "therond 2013", "2013 .

ptch mediated", ".

ptch mediated inhibition", "mediated inhibition of", "inhibition of smo", "of smo is", "smo is relieved", "is relieved upon", "relieved upon ligand", "upon ligand stimulation", "ligand stimulation of", "stimulation of ptch", "ptch but", "but the mechanisms", "the mechanisms for", "mechanisms for this", "for this relief", "this relief are", "relief are again", "are again unknown.", "again unknown. smo", "unknown. smo and", "smo and ptch", "and ptch appear", "ptch appear to", "appear to have", "to have opposing", "have opposing localizations", "opposing localizations in", "localizations in both", "in both the", "both the 'off'", "the 'off' and", "'off' and 'on'", "and 'on' state", "state with", "with ptch exiting", "ptch exiting and", "exiting and smo", "and smo entering", "smo entering the", "entering the cilium", "the cilium upon", "cilium upon hh", "upon hh pathway", "hh pathway activation", "activation denef", "denef et al", "al 2000", "2000 rohatgi", "rohatgi et al", "al 2007", "2007 reviewed", "reviewed in goetz", "in goetz and", "goetz and anderson", "anderson 2010", "2010 hui", "hui and angers", "angers 2011", "2011 . activation", ". activation of", "of smo involves", "smo involves a", "involves a conserved", "a conserved phosphorylation", "conserved phosphorylation mediated", "phosphorylation mediated conformational", "mediated conformational change", "conformational change in", "change in the", "in the c", "the c terminal", "c terminal tails", "terminal tails that", "tails that destabilizes", "that destabilizes an", "destabilizes an intramolecular", "an intramolecular interaction", "intramolecular interaction and", "interaction and promotes", "and promotes the", "promotes the interaction", "the interaction between", "interaction between adjacent", "between adjacent tails", "adjacent tails in", "tails in the", "in the smo", "the smo dimer.", "dimer. in", "drosophila this", "this phosphorylation is", "phosphorylation is mediated", "is mediated by", "mediated by pka", "by pka and", "pka and ck1", "ck1 while", "while in vertebrates", "in vertebrates it", "vertebrates it appears", "it appears to", "appears to involve", "to involve adrbk1/grk2", "involve adrbk1/grk2 and", "adrbk1/grk2 and csnk1a1.", "and csnk1a1. sequential", "csnk1a1. sequential phosphorylations", "sequential phosphorylations along", "phosphorylations along multiple", "along multiple serine", "multiple serine and", "serine and threonine", "and threonine motifs", "threonine motifs in", "motifs in the", "the smo c", "smo c terminal", "c terminal tail", "terminal tail appear", "tail appear to", "appear to allow", "to allow a", "allow a graded", "a graded response", "graded response to", "to hh ligand", "hh ligand concentration", "ligand concentration in", "concentration in both", "in both flies", "both flies and", "flies and vertebrates", "vertebrates zhao", "zhao et al", "2007 chen", "chen et al", "al 2010", "2010 chen", "al 2011", "flies smo", "terminal tail phosphorylation", "tail phosphorylation promotes", "phosphorylation promotes an", "promotes an association", "an association with", "association with the", "with the hedgehog", "the hedgehog signaling", "hedgehog signaling complex", "complex hsc", "hsc through", "through interaction with", "interaction with the", "with the scaffolding", "the scaffolding kinesin", "scaffolding kinesin 2", "kinesin 2 like", "2 like protein", "like protein cos2", "cos2 activating", "activating the fu", "the fu kinase", "fu kinase and", "kinase and ultimately", "and ultimately releasing", "ultimately releasing uncleaved", "releasing uncleaved ci", "uncleaved ci from", "ci from the", "from the complex", "complex zhang", "zhang et al", "al 2005", "2005 ogden", "ogden et al", "al 2003", "2003 lum", "lum et al", "2003 reviewed", "reviewed in mukhopadhyay", "in mukhopadhyay and", "mukhopadhyay and rohatgi", "rohatgi 2014", "2014 . in", ". in vertebrates", "vertebrates smo", "tail phosphorylation and", "phosphorylation and conformational", "and conformational change", "conformational change is", "change is linked", "is linked to", "linked to its", "to its kif7", "its kif7 dependent", "kif7 dependent ciliary", "dependent ciliary accumulation", "2011 zhao", "in the cilium", "cilium smo", "smo is restricted", "is restricted to", "restricted to a", "to a transition", "a transition zone", "transition zone proximal", "zone proximal region", "proximal region known", "region known as", "known as the", "as the evc", "the evc zone", "zone yang", "yang et al", "al 2012", "2012 blair", "blair et al", "2011 pusapati", "pusapati et al", "al 2014", "2014 reviewed", "reviewed in eggenschwiler", "in eggenschwiler 2012", "eggenschwiler 2012 .", "2012 . both", ". both smo", "both smo phosphorylation", "smo phosphorylation and", "phosphorylation and its", "and its ciliary", "its ciliary localization", "ciliary localization are", "localization are required", "are required to", "required to promote", "to promote the", "promote the hh", "the hh dependent", "hh dependent dissociation", "dependent dissociation of", "dissociation of the", "of the gli:sufu", "the gli:sufu complex", "complex ultimately", "ultimately allowing full", "allowing full length", "full length gli", "length gli transcription", "gli transcription factors", "transcription factors to", "factors to translocate", "to translocate to", "translocate to the", "to the nucleus", "the nucleus to", "nucleus to activate", "to activate hh", "activate hh responsive", "hh responsive genes", "genes reviewed", "reviewed in briscoe", "in briscoe and", "activation of the transmembrane", "of the transmembrane protein", "the transmembrane protein smo", "transmembrane protein smo in", "protein smo in response", "smo in response to", "in response to hh", "response to hh stimulation", "to hh stimulation is", "hh stimulation is a", "stimulation is a major", "is a major control", "a major control point", "major control point in", "control point in the", "point in the hh", "in the hh signaling", "the hh signaling pathway", "signaling pathway reviewed", "pathway reviewed in", "reviewed in ayers and", "in ayers and therond", "and therond 2010", "2010 jiang and", "and hui 2008", "hui 2008 .", "2008 . in the", ". in the absence", "in the absence of", "the absence of ligand", "of ligand smo", "ligand smo is", "smo is inhibited in", "is inhibited in an", "inhibited in an unknown", "in an unknown manner", "an unknown manner by", "unknown manner by the", "manner by the hh", "by the hh receptor", "the hh receptor ptch.", "hh receptor ptch. ptch", "receptor ptch. ptch regulates", "ptch. ptch regulates smo", "ptch regulates smo in", "regulates smo in a", "smo in a non", "in a non stoichiometric", "a non stoichiometric manner", "non stoichiometric manner and", "stoichiometric manner and there", "manner and there is", "and there is little", "there is little evidence", "is little evidence that", "little evidence that endogenous", "evidence that endogenous ptch", "that endogenous ptch and", "endogenous ptch and smo", "ptch and smo interact", "and smo interact directly", "interact directly taipale", "directly taipale et", "et al 2002", "2002 reviewed in", "reviewed in huangfu and", "in huangfu and anderson", "and anderson 2006", "anderson 2006 .", "2006 . ptch may", ". ptch may regulate", "ptch may regulate smo", "may regulate smo activity", "regulate smo activity by", "smo activity by controlling", "activity by controlling the", "by controlling the flux", "controlling the flux of", "the flux of sterol", "flux of sterol related", "of sterol related smo", "sterol related smo agonists", "related smo agonists and/or", "smo agonists and/or antagonists", "and/or antagonists although", "antagonists although this", "although this has not", "this has not been", "has not been fully", "not been fully substantiated", "fully substantiated khaliullina", "substantiated khaliullina et", "et al 2009", "2009 reviewed in", "reviewed in rohatgi and", "in rohatgi and scott", "and scott 2007", "2007 briscoe and", "and therond 2013", "therond 2013 .

ptch", "2013 .

ptch mediated inhibition", ".

ptch mediated inhibition of", "mediated inhibition of smo", "inhibition of smo is", "of smo is relieved", "smo is relieved upon", "is relieved upon ligand", "relieved upon ligand stimulation", "upon ligand stimulation of", "ligand stimulation of ptch", "of ptch but", "ptch but the", "but the mechanisms for", "the mechanisms for this", "mechanisms for this relief", "for this relief are", "this relief are again", "relief are again unknown.", "are again unknown. smo", "again unknown. smo and", "unknown. smo and ptch", "smo and ptch appear", "and ptch appear to", "ptch appear to have", "appear to have opposing", "to have opposing localizations", "have opposing localizations in", "opposing localizations in both", "localizations in both the", "in both the 'off'", "both the 'off' and", "the 'off' and 'on'", "'off' and 'on' state", "'on' state with", "state with ptch", "with ptch exiting and", "ptch exiting and smo", "exiting and smo entering", "and smo entering the", "smo entering the cilium", "entering the cilium upon", "the cilium upon hh", "cilium upon hh pathway", "upon hh pathway activation", "pathway activation denef", "activation denef et", "et al 2000", "2000 rohatgi et", "et al 2007", "2007 reviewed in", "reviewed in goetz and", "in goetz and anderson", "and anderson 2010", "2010 hui and", "and angers 2011", "angers 2011 .", "2011 . activation of", ". activation of smo", "activation of smo involves", "of smo involves a", "smo involves a conserved", "involves a conserved phosphorylation", "a conserved phosphorylation mediated", "conserved phosphorylation mediated conformational", "phosphorylation mediated conformational change", "mediated conformational change in", "conformational change in the", "change in the c", "in the c terminal", "the c terminal tails", "c terminal tails that", "terminal tails that destabilizes", "tails that destabilizes an", "that destabilizes an intramolecular", "destabilizes an intramolecular interaction", "an intramolecular interaction and", "intramolecular interaction and promotes", "interaction and promotes the", "and promotes the interaction", "promotes the interaction between", "the interaction between adjacent", "interaction between adjacent tails", "between adjacent tails in", "adjacent tails in the", "tails in the smo", "in the smo dimer.", "smo dimer. in", "dimer. in drosophila", "in drosophila this", "drosophila this phosphorylation", "this phosphorylation is mediated", "phosphorylation is mediated by", "is mediated by pka", "mediated by pka and", "by pka and ck1", "and ck1 while", "ck1 while in", "while in vertebrates it", "in vertebrates it appears", "vertebrates it appears to", "it appears to involve", "appears to involve adrbk1/grk2", "to involve adrbk1/grk2 and", "involve adrbk1/grk2 and csnk1a1.", "adrbk1/grk2 and csnk1a1. sequential", "and csnk1a1. sequential phosphorylations", "csnk1a1. sequential phosphorylations along", "sequential phosphorylations along multiple", "phosphorylations along multiple serine", "along multiple serine and", "multiple serine and threonine", "serine and threonine motifs", "and threonine motifs in", "threonine motifs in the", "motifs in the smo", "in the smo c", "the smo c terminal", "smo c terminal tail", "c terminal tail appear", "terminal tail appear to", "tail appear to allow", "appear to allow a", "to allow a graded", "allow a graded response", "a graded response to", "graded response to hh", "response to hh ligand", "to hh ligand concentration", "hh ligand concentration in", "ligand concentration in both", "concentration in both flies", "in both flies and", "both flies and vertebrates", "and vertebrates zhao", "vertebrates zhao et", "2007 chen et", "et al 2010", "2010 chen et", "et al 2011", "al 2011 .", "2011 . in", ". in flies", "in flies smo", "flies smo c", "c terminal tail phosphorylation", "terminal tail phosphorylation promotes", "tail phosphorylation promotes an", "phosphorylation promotes an association", "promotes an association with", "an association with the", "association with the hedgehog", "with the hedgehog signaling", "the hedgehog signaling complex", "signaling complex hsc", "hsc through interaction", "through interaction with the", "interaction with the scaffolding", "with the scaffolding kinesin", "the scaffolding kinesin 2", "scaffolding kinesin 2 like", "kinesin 2 like protein", "2 like protein cos2", "protein cos2 activating", "cos2 activating the", "activating the fu kinase", "the fu kinase and", "fu kinase and ultimately", "kinase and ultimately releasing", "and ultimately releasing uncleaved", "ultimately releasing uncleaved ci", "releasing uncleaved ci from", "uncleaved ci from the", "ci from the complex", "the complex zhang", "complex zhang et", "et al 2005", "2005 ogden et", "et al 2003", "2003 lum et", "2003 reviewed in", "reviewed in mukhopadhyay and", "in mukhopadhyay and rohatgi", "and rohatgi 2014", "rohatgi 2014 .", "2014 . in vertebrates", "in vertebrates smo", "vertebrates smo c", "terminal tail phosphorylation and", "tail phosphorylation and conformational", "phosphorylation and conformational change", "and conformational change is", "conformational change is linked", "change is linked to", "is linked to its", "linked to its kif7", "to its kif7 dependent", "its kif7 dependent ciliary", "kif7 dependent ciliary accumulation", "accumulation chen", "2011 zhao et", "al 2010 .", "2010 . in", "the cilium smo", "cilium smo is", "smo is restricted to", "is restricted to a", "restricted to a transition", "to a transition zone", "a transition zone proximal", "transition zone proximal region", "zone proximal region known", "proximal region known as", "region known as the", "known as the evc", "as the evc zone", "evc zone yang", "zone yang et", "et al 2012", "2012 blair et", "2011 pusapati et", "et al 2014", "2014 reviewed in", "reviewed in eggenschwiler 2012", "in eggenschwiler 2012 .", "eggenschwiler 2012 . both", "2012 . both smo", ". both smo phosphorylation", "both smo phosphorylation and", "smo phosphorylation and its", "phosphorylation and its ciliary", "and its ciliary localization", "its ciliary localization are", "ciliary localization are required", "localization are required to", "are required to promote", "required to promote the", "to promote the hh", "promote the hh dependent", "the hh dependent dissociation", "hh dependent dissociation of", "dependent dissociation of the", "dissociation of the gli:sufu", "of the gli:sufu complex", "gli:sufu complex ultimately", "complex ultimately allowing", "ultimately allowing full length", "allowing full length gli", "full length gli transcription", "length gli transcription factors", "gli transcription factors to", "transcription factors to translocate", "factors to translocate to", "to translocate to the", "translocate to the nucleus", "to the nucleus to", "the nucleus to activate", "nucleus to activate hh", "to activate hh responsive", "activate hh responsive genes", "responsive genes reviewed", "genes reviewed in", "reviewed in briscoe and", "in briscoe and therond", "therond 2013 .


", "activation of the transmembrane protein", "of the transmembrane protein smo", "the transmembrane protein smo in", "transmembrane protein smo in response", "protein smo in response to", "smo in response to hh", "in response to hh stimulation", "response to hh stimulation is", "to hh stimulation is a", "hh stimulation is a major", "stimulation is a major control", "is a major control point", "a major control point in", "major control point in the", "control point in the hh", "point in the hh signaling", "in the hh signaling pathway", "hh signaling pathway reviewed", "signaling pathway reviewed in", "pathway reviewed in ayers", "reviewed in ayers and therond", "ayers and therond 2010", "therond 2010 jiang", "2010 jiang and hui", "jiang and hui 2008", "and hui 2008 .", "hui 2008 . in", "2008 . in the absence", ". in the absence of", "in the absence of ligand", "absence of ligand smo", "of ligand smo is", "ligand smo is inhibited", "smo is inhibited in an", "is inhibited in an unknown", "inhibited in an unknown manner", "in an unknown manner by", "an unknown manner by the", "unknown manner by the hh", "manner by the hh receptor", "by the hh receptor ptch.", "the hh receptor ptch. ptch", "hh receptor ptch. ptch regulates", "receptor ptch. ptch regulates smo", "ptch. ptch regulates smo in", "ptch regulates smo in a", "regulates smo in a non", "smo in a non stoichiometric", "in a non stoichiometric manner", "a non stoichiometric manner and", "non stoichiometric manner and there", "stoichiometric manner and there is", "manner and there is little", "and there is little evidence", "there is little evidence that", "is little evidence that endogenous", "little evidence that endogenous ptch", "evidence that endogenous ptch and", "that endogenous ptch and smo", "endogenous ptch and smo interact", "ptch and smo interact directly", "smo interact directly taipale", "interact directly taipale et", "directly taipale et al", "taipale et al 2002", "al 2002 reviewed", "2002 reviewed in huangfu", "reviewed in huangfu and anderson", "huangfu and anderson 2006", "and anderson 2006 .", "anderson 2006 . ptch", "2006 . ptch may regulate", ". ptch may regulate smo", "ptch may regulate smo activity", "may regulate smo activity by", "regulate smo activity by controlling", "smo activity by controlling the", "activity by controlling the flux", "by controlling the flux of", "controlling the flux of sterol", "the flux of sterol related", "flux of sterol related smo", "of sterol related smo agonists", "sterol related smo agonists and/or", "related smo agonists and/or antagonists", "agonists and/or antagonists although", "and/or antagonists although this", "antagonists although this has", "although this has not been", "this has not been fully", "has not been fully substantiated", "been fully substantiated khaliullina", "fully substantiated khaliullina et", "substantiated khaliullina et al", "khaliullina et al 2009", "al 2009 reviewed", "2009 reviewed in rohatgi", "reviewed in rohatgi and scott", "rohatgi and scott 2007", "scott 2007 briscoe", "2007 briscoe and therond", "briscoe and therond 2013", "and therond 2013 .

ptch", "therond 2013 .

ptch mediated", "2013 .

ptch mediated inhibition of", ".

ptch mediated inhibition of smo", "mediated inhibition of smo is", "inhibition of smo is relieved", "of smo is relieved upon", "smo is relieved upon ligand", "is relieved upon ligand stimulation", "relieved upon ligand stimulation of", "upon ligand stimulation of ptch", "stimulation of ptch but", "of ptch but the", "ptch but the mechanisms", "but the mechanisms for this", "the mechanisms for this relief", "mechanisms for this relief are", "for this relief are again", "this relief are again unknown.", "relief are again unknown. smo", "are again unknown. smo and", "again unknown. smo and ptch", "unknown. smo and ptch appear", "smo and ptch appear to", "and ptch appear to have", "ptch appear to have opposing", "appear to have opposing localizations", "to have opposing localizations in", "have opposing localizations in both", "opposing localizations in both the", "localizations in both the 'off'", "in both the 'off' and", "both the 'off' and 'on'", "the 'off' and 'on' state", "and 'on' state with", "'on' state with ptch", "state with ptch exiting", "with ptch exiting and smo", "ptch exiting and smo entering", "exiting and smo entering the", "and smo entering the cilium", "smo entering the cilium upon", "entering the cilium upon hh", "the cilium upon hh pathway", "cilium upon hh pathway activation", "hh pathway activation denef", "pathway activation denef et", "activation denef et al", "denef et al 2000", "al 2000 rohatgi", "2000 rohatgi et al", "rohatgi et al 2007", "al 2007 reviewed", "2007 reviewed in goetz", "reviewed in goetz and anderson", "goetz and anderson 2010", "anderson 2010 hui", "2010 hui and angers", "hui and angers 2011", "and angers 2011 .", "angers 2011 . activation", "2011 . activation of smo", ". activation of smo involves", "activation of smo involves a", "of smo involves a conserved", "smo involves a conserved phosphorylation", "involves a conserved phosphorylation mediated", "a conserved phosphorylation mediated conformational", "conserved phosphorylation mediated conformational change", "phosphorylation mediated conformational change in", "mediated conformational change in the", "conformational change in the c", "change in the c terminal", "in the c terminal tails", "the c terminal tails that", "c terminal tails that destabilizes", "terminal tails that destabilizes an", "tails that destabilizes an intramolecular", "that destabilizes an intramolecular interaction", "destabilizes an intramolecular interaction and", "an intramolecular interaction and promotes", "intramolecular interaction and promotes the", "interaction and promotes the interaction", "and promotes the interaction between", "promotes the interaction between adjacent", "the interaction between adjacent tails", "interaction between adjacent tails in", "between adjacent tails in the", "adjacent tails in the smo", "tails in the smo dimer.", "the smo dimer. in", "smo dimer. in drosophila", "in drosophila this phosphorylation", "drosophila this phosphorylation is", "this phosphorylation is mediated by", "phosphorylation is mediated by pka", "is mediated by pka and", "mediated by pka and ck1", "pka and ck1 while", "and ck1 while in", "ck1 while in vertebrates", "while in vertebrates it appears", "in vertebrates it appears to", "vertebrates it appears to involve", "it appears to involve adrbk1/grk2", "appears to involve adrbk1/grk2 and", "to involve adrbk1/grk2 and csnk1a1.", "involve adrbk1/grk2 and csnk1a1. sequential", "adrbk1/grk2 and csnk1a1. sequential phosphorylations", "and csnk1a1. sequential phosphorylations along", "csnk1a1. sequential phosphorylations along multiple", "sequential phosphorylations along multiple serine", "phosphorylations along multiple serine and", "along multiple serine and threonine", "multiple serine and threonine motifs", "serine and threonine motifs in", "and threonine motifs in the", "threonine motifs in the smo", "motifs in the smo c", "in the smo c terminal", "the smo c terminal tail", "smo c terminal tail appear", "c terminal tail appear to", "terminal tail appear to allow", "tail appear to allow a", "appear to allow a graded", "to allow a graded response", "allow a graded response to", "a graded response to hh", "graded response to hh ligand", "response to hh ligand concentration", "to hh ligand concentration in", "hh ligand concentration in both", "ligand concentration in both flies", "concentration in both flies and", "in both flies and vertebrates", "flies and vertebrates zhao", "and vertebrates zhao et", "vertebrates zhao et al", "zhao et al 2007", "al 2007 chen", "2007 chen et al", "chen et al 2010", "al 2010 chen", "2010 chen et al", "chen et al 2011", "et al 2011 .", "2011 . in flies", "in flies smo c", "flies smo c terminal", "smo c terminal tail phosphorylation", "c terminal tail phosphorylation promotes", "terminal tail phosphorylation promotes an", "tail phosphorylation promotes an association", "phosphorylation promotes an association with", "promotes an association with the", "an association with the hedgehog", "association with the hedgehog signaling", "with the hedgehog signaling complex", "hedgehog signaling complex hsc", "complex hsc through", "hsc through interaction with", "through interaction with the scaffolding", "interaction with the scaffolding kinesin", "with the scaffolding kinesin 2", "the scaffolding kinesin 2 like", "scaffolding kinesin 2 like protein", "kinesin 2 like protein cos2", "like protein cos2 activating", "protein cos2 activating the", "cos2 activating the fu", "activating the fu kinase and", "the fu kinase and ultimately", "fu kinase and ultimately releasing", "kinase and ultimately releasing uncleaved", "and ultimately releasing uncleaved ci", "ultimately releasing uncleaved ci from", "releasing uncleaved ci from the", "uncleaved ci from the complex", "from the complex zhang", "the complex zhang et", "complex zhang et al", "zhang et al 2005", "al 2005 ogden", "2005 ogden et al", "ogden et al 2003", "al 2003 lum", "2003 lum et al", "lum et al 2003", "al 2003 reviewed", "2003 reviewed in mukhopadhyay", "reviewed in mukhopadhyay and rohatgi", "mukhopadhyay and rohatgi 2014", "and rohatgi 2014 .", "rohatgi 2014 . in", ". in vertebrates smo", "in vertebrates smo c", "vertebrates smo c terminal", "c terminal tail phosphorylation and", "terminal tail phosphorylation and conformational", "tail phosphorylation and conformational change", "phosphorylation and conformational change is", "and conformational change is linked", "conformational change is linked to", "change is linked to its", "is linked to its kif7", "linked to its kif7 dependent", "to its kif7 dependent ciliary", "its kif7 dependent ciliary accumulation", "ciliary accumulation chen", "accumulation chen et", "al 2011 zhao", "2011 zhao et al", "et al 2010 .", "2010 . in the", ". in the cilium", "in the cilium smo", "the cilium smo is", "cilium smo is restricted", "smo is restricted to a", "is restricted to a transition", "restricted to a transition zone", "to a transition zone proximal", "a transition zone proximal region", "transition zone proximal region known", "zone proximal region known as", "proximal region known as the", "region known as the evc", "known as the evc zone", "the evc zone yang", "evc zone yang et", "zone yang et al", "yang et al 2012", "al 2012 blair", "2012 blair et al", "blair et al 2011", "al 2011 pusapati", "2011 pusapati et al", "pusapati et al 2014", "al 2014 reviewed", "2014 reviewed in eggenschwiler", "reviewed in eggenschwiler 2012 .", "in eggenschwiler 2012 . both", "eggenschwiler 2012 . both smo", "2012 . both smo phosphorylation", ". both smo phosphorylation and", "both smo phosphorylation and its", "smo phosphorylation and its ciliary", "phosphorylation and its ciliary localization", "and its ciliary localization are", "its ciliary localization are required", "ciliary localization are required to", "localization are required to promote", "are required to promote the", "required to promote the hh", "to promote the hh dependent", "promote the hh dependent dissociation", "the hh dependent dissociation of", "hh dependent dissociation of the", "dependent dissociation of the gli:sufu", "dissociation of the gli:sufu complex", "the gli:sufu complex ultimately", "gli:sufu complex ultimately allowing", "complex ultimately allowing full", "ultimately allowing full length gli", "allowing full length gli transcription", "full length gli transcription factors", "length gli transcription factors to", "gli transcription factors to translocate", "transcription factors to translocate to", "factors to translocate to the", "to translocate to the nucleus", "translocate to the nucleus to", "to the nucleus to activate", "the nucleus to activate hh", "nucleus to activate hh responsive", "to activate hh responsive genes", "hh responsive genes reviewed", "responsive genes reviewed in", "genes reviewed in briscoe", "reviewed in briscoe and therond", "and therond 2013 .


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"fieldtype": "text", "phraselist": [ "signaling by", "by fgfr1", "fgfr1 in", "in disease", "signaling by fgfr1", "by fgfr1 in", "fgfr1 in disease", "signaling by fgfr1 in", "by fgfr1 in disease", "signaling by fgfr1 in disease", "the fgfr1", "fgfr1 gene", "gene has", "has been", "been shown", "shown to", "to be", "be subject", "subject to", "to activating", "activating mutations", "chromosomal rearrangements", "rearrangements and", "and gene", "gene amplification", "amplification leading", "leading to", "to a", "a variety", "variety of", "of proliferative", "proliferative and", "and developmental", "developmental disorders", "disorders depending", "depending on", "on whether", "whether these", "these events", "events occur", "occur in", "in the", "the germline", "germline or", "or arise", "arise somatically", "reviewed in", "in webster", "webster and", "and donoghue", "greulich and", "and pollock", "2011 .", "


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in", ".

in contrast", "is a", "a target", "target of", "of chromosomal", "rearrangements in", "a number", "of cancers.", "fgfr1 has", "be recurrently", "recurrently translocated", "translocated in", "the 8p11", "8p11 myeloproliferative", "myeloproliferative syndrome", "a pre", "pre leukemic", "leukemic condition", "condition also", "also known", "known as", "as stem", "stem cell", "cell leukemia/lymphoma", "that rapidly", "rapidly progresses", "progresses to", "to leukemia.", "this translocation", "translocation fuses", "fuses the", "the kinase", "domain of", "of fgfr1", "fgfr1 with", "the dimerization", "dimerization domain", "of one", "one of", "of 10", "10 identified", "identified fusion", "fusion partners", "resulting in", "the constitutive", "constitutive dimerization", "dimerization and", "and activation", "activation of", "in jackson", "2010 .", "

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more", "established.
more recently", "fgfr1 fusion", "fusion proteins", "proteins have", "these are", "are thought", "to undergo", "undergo constitutive", "constitutive ligand", "ligand independent", "independent dimerization", "activation based", "based on", "on dimerization", "dimerization motifs", "motifs found", "found in", "the fusion", "in parker", "2014 .", "the fgfr1 gene", "fgfr1 gene has", "gene has been", "has been shown", "been shown to", "shown to be", "to be subject", "be subject to", "subject to activating", "to activating mutations", "mutations chromosomal", "chromosomal rearrangements and", "rearrangements and gene", "and gene amplification", "gene amplification leading", "amplification leading to", "leading to a", "to a variety", "a variety of", "variety of proliferative", "of proliferative and", "proliferative and developmental", "and developmental disorders", "developmental disorders depending", "disorders depending on", "depending on whether", "on whether these", "whether these events", "these events occur", "events occur in", "occur in the", "in the germline", "the germline or", "germline or arise", "or arise somatically", "somatically reviewed", "reviewed in webster", "in webster and", "webster and donoghue", "donoghue 1997", "1997 burke", "burke 1998", "1998 cunningham", "cunningham 2007", "2007 wesche", "wesche 2011", "2011 greulich", "greulich and pollock", "pollock 2011", ".


activating", "


activating mutation p252r", "mutation p252r in", "p252r in fgfr1", "in fgfr1 is", "fgfr1 is associated", "is associated with", "associated with the", "with the development", "the development of", "development of pfeiffer", "of pfeiffer syndrome", "syndrome characterized", "characterized by craniosynostosis", "craniosynostosis premature", "premature fusion of", "fusion of several", "of several sutures", "several sutures in", "sutures in the", "in the skull", "skull and", "and broadened thumbs", "broadened thumbs and", "thumbs and toes", "toes muenke", "muenke 1994", "1994 reviewed", "reviewed in cunningham", ". this", "this residue falls", "residue falls in", "falls in a", "in a highly", "a highly conserved", "highly conserved pro", "conserved pro ser", "pro ser dipeptide", "ser dipeptide between", "dipeptide between the", "between the second", "the second and", "second and third", "and third ig", "third ig domains", "ig domains of", "domains of the", "of the extracellular", "the extracellular region", "extracellular region of", "region of the", "of the receptor.", "the receptor. the", "receptor. the mutation", "the mutation is", "mutation is thought", "is thought to", "thought to increase", "to increase the", "increase the number", "the number of", "number of hydrogen", "of hydrogen bonds", "hydrogen bonds formed", "bonds formed with", "formed with the", "with the ligand", "the ligand and", "ligand and to", "and to thereby", "to thereby increase", "thereby increase ligand", "increase ligand binding", "ligand binding affinity", "affinity ibrahimi", "ibrahimi 2004a", "2004a . unlike", ". unlike other", "unlike other fgf", "other fgf receptors", "receptors few", "few activating point", "activating point mutations", "point mutations in", "mutations in the", "in the fgfr1", "the fgfr1 coding", "fgfr1 coding sequence", "coding sequence have", "sequence have been", "have been identified", "been identified in", "identified in cancer.", "cancer. point", "in the ig", "the ig ii", "ig ii iii", "ii iii linker", "iii linker analagous", "linker analagous to", "analagous to the", "to the p252r", "the p252r pfeiffer", "p252r pfeiffer syndrome", "pfeiffer syndrome mutation", "syndrome mutation have", "mutation have been", "identified in lung", "in lung cancer", "lung cancer and", "cancer and melanoma", "melanoma ruhe", "ruhe 2007", "2007 davies", "davies 2005", "and two kinase", "two kinase domain", "kinase domain mutations", "domain mutations in", "mutations in fgfr1", "in fgfr1 have", "fgfr1 have been", "identified in glioblastoma", "glioblastoma rand", "rand 2005", "2005 network", "tcga 2008", "2008 .

in contrast", "fgfr1 is a", "is a target", "a target of", "target of chromosomal", "of chromosomal rearrangements", "chromosomal rearrangements in", "rearrangements in a", "in a number", "a number of", "number of cancers.", "cancers. fgfr1", "fgfr1 has been", "to be recurrently", "be recurrently translocated", "recurrently translocated in", "translocated in the", "in the 8p11", "the 8p11 myeloproliferative", "8p11 myeloproliferative syndrome", "syndrome ems", "a pre leukemic", "pre leukemic condition", "leukemic condition also", "condition also known", "also known as", "known as stem", "as stem cell", "stem cell leukemia/lymphoma", "leukemia/lymphoma scll", "scll that", "that rapidly progresses", "rapidly progresses to", "progresses to leukemia.", "leukemia. this", "this translocation fuses", "translocation fuses the", "fuses the kinase", "the kinase domain", "kinase domain of", "domain of fgfr1", "of fgfr1 with", "fgfr1 with the", "with the dimerization", "the dimerization domain", "dimerization domain of", "domain of one", "of one of", "one of 10", "of 10 identified", "10 identified fusion", "identified fusion partners", "partners resulting", "resulting in the", "in the constitutive", "the constitutive dimerization", "constitutive dimerization and", "dimerization and activation", "and activation of", "activation of the", "of the kinase", "kinase reviewed", "reviewed in jackson", "jackson 2010", ".

amplification", "

amplification of the", "of the fgfr1", "has been implicated", "been implicated as", "implicated as a", "as a oncogenic", "a oncogenic factor", "oncogenic factor in", "factor in a", "in a range", "a range of", "range of cancers", "cancers including", "breast ovarian", "ovarian bladder", "bladder lung", "lung oral", "oral squamous carcinomas", "carcinomas and", "rhabdomyosarcoma reviewed", "reviewed in turner", "in turner and", "turner and grose", "grose 2010", "2010 wesche", "although there are", "there are other", "are other candidate", "other candidate genes", "candidate genes in", "genes in the", "in the amplified", "the amplified region", "amplified region and", "region and the", "and the definitive", "the definitive role", "definitive role of", "role of fgfr1", "of fgfr1 has", "fgfr1 has not", "has not been", "not been fully", "been fully established.
more", "fully established.
more recently", "recently fgfr1", "fgfr1 fusion proteins", "fusion proteins have", "proteins have been", "identified in a", "number of cancers", "cancers these", "these are thought", "are thought to", "thought to undergo", "to undergo constitutive", "undergo constitutive ligand", "constitutive ligand independent", "ligand independent dimerization", "independent dimerization and", "and activation based", "activation based on", "based on dimerization", "on dimerization motifs", "dimerization motifs found", "motifs found in", "found in the", "in the fusion", "the fusion partners", "partners reviewed", "reviewed in parker", "parker 2014", "the fgfr1 gene has", "fgfr1 gene has been", "gene has been shown", "has been shown to", "been shown to be", "shown to be subject", "to be subject to", "be subject to activating", "subject to activating mutations", "activating mutations chromosomal", "mutations chromosomal rearrangements", "chromosomal rearrangements and gene", "rearrangements and gene amplification", "and gene amplification leading", "gene amplification leading to", "amplification leading to a", "leading to a variety", "to a variety of", "a variety of proliferative", "variety of proliferative and", "of proliferative and developmental", "proliferative and developmental disorders", "and developmental disorders depending", "developmental disorders depending on", "disorders depending on whether", "depending on whether these", "on whether these events", "whether these events occur", "these events occur in", "events occur in the", "occur in the germline", "in the germline or", "the germline or arise", "germline or arise somatically", "arise somatically reviewed", "somatically reviewed in", "reviewed in webster and", "in webster and donoghue", "and donoghue 1997", "2011 greulich and", "and pollock 2011", "pollock 2011 .", "2011 .


activating", ".


activating mutation", "


activating mutation p252r in", "mutation p252r in fgfr1", "p252r in fgfr1 is", "in fgfr1 is associated", "fgfr1 is associated with", "is associated with the", "associated with the development", "with the development of", "the development of pfeiffer", "development of pfeiffer syndrome", "pfeiffer syndrome characterized", "syndrome characterized by", "by craniosynostosis premature", "craniosynostosis premature fusion", "premature fusion of several", "fusion of several sutures", "of several sutures in", "several sutures in the", "sutures in the skull", "the skull and", "skull and broadened", "and broadened thumbs and", "broadened thumbs and toes", "and toes muenke", "1994 reviewed in", "in cunningham 2007", "cunningham 2007 .", "2007 . this", ". this residue", "this residue falls in", "residue falls in a", "falls in a highly", "in a highly conserved", "a highly conserved pro", "highly conserved pro ser", "conserved pro ser dipeptide", "pro ser dipeptide between", "ser dipeptide between the", "dipeptide between the second", "between the second and", "the second and third", "second and third ig", "and third ig domains", "third ig domains of", "ig domains of the", "domains of the extracellular", "of the extracellular region", "the extracellular region of", "extracellular region of the", "region of the receptor.", "of the receptor. the", "the receptor. the mutation", "receptor. the mutation is", "the mutation is thought", "mutation is thought to", "is thought to increase", "thought to increase the", "to increase the number", "increase the number of", "the number of hydrogen", "number of hydrogen bonds", "of hydrogen bonds formed", "hydrogen bonds formed with", "bonds formed with the", "formed with the ligand", "with the ligand and", "the ligand and to", "ligand and to thereby", "and to thereby increase", "to thereby increase ligand", "thereby increase ligand binding", "increase ligand binding affinity", "binding affinity ibrahimi", "ibrahimi 2004a .", "2004a . unlike other", ". unlike other fgf", "unlike other fgf receptors", "fgf receptors few", "receptors few activating", "few activating point mutations", "activating point mutations in", "point mutations in the", "mutations in the fgfr1", "in the fgfr1 coding", "the fgfr1 coding sequence", "fgfr1 coding sequence have", "coding sequence have been", "sequence have been identified", "have been identified in", "been identified in cancer.", "in cancer. point", "cancer. point mutations", "mutations in the ig", "in the ig ii", "the ig ii iii", "ig ii iii linker", "ii iii linker analagous", "iii linker analagous to", "linker analagous to the", "analagous to the p252r", "to the p252r pfeiffer", "the p252r pfeiffer syndrome", "p252r pfeiffer syndrome mutation", "pfeiffer syndrome mutation have", "syndrome mutation have been", "mutation have been identified", "been identified in lung", "identified in lung cancer", "in lung cancer and", "lung cancer and melanoma", "and melanoma ruhe", "2005 and", "and two kinase domain", "two kinase domain mutations", "kinase domain mutations in", "domain mutations in fgfr1", "mutations in fgfr1 have", "in fgfr1 have been", "fgfr1 have been identified", "been identified in glioblastoma", "in glioblastoma rand", "2005 network tcga", "network tcga 2008", "tcga 2008 .

in", "contrast fgfr1", "fgfr1 is a target", "is a target of", "a target of chromosomal", "target of chromosomal rearrangements", "of chromosomal rearrangements in", "chromosomal rearrangements in a", "rearrangements in a number", "in a number of", "a number of cancers.", "of cancers. fgfr1", "cancers. fgfr1 has", "fgfr1 has been shown", "shown to be recurrently", "to be recurrently translocated", "be recurrently translocated in", "recurrently translocated in the", "translocated in the 8p11", "in the 8p11 myeloproliferative", "the 8p11 myeloproliferative syndrome", "myeloproliferative syndrome ems", "ems a", "a pre leukemic condition", "pre leukemic condition also", "leukemic condition also known", "condition also known as", "also known as stem", "known as stem cell", "as stem cell leukemia/lymphoma", "cell leukemia/lymphoma scll", "scll that rapidly", "that rapidly progresses to", "rapidly progresses to leukemia.", "to leukemia. this", "leukemia. this translocation", "this translocation fuses the", "translocation fuses the kinase", "fuses the kinase domain", "the kinase domain of", "kinase domain of fgfr1", "domain of fgfr1 with", "of fgfr1 with the", "fgfr1 with the dimerization", "with the dimerization domain", "the dimerization domain of", "dimerization domain of one", "domain of one of", "of one of 10", "one of 10 identified", "of 10 identified fusion", "10 identified fusion partners", "fusion partners resulting", "partners resulting in", "resulting in the constitutive", "in the constitutive dimerization", "the constitutive dimerization and", "constitutive dimerization and activation", "dimerization and activation of", "and activation of the", "activation of the kinase", "the kinase reviewed", "kinase reviewed in", "in jackson 2010", "jackson 2010 .", "2010 .

amplification", ".

amplification of", "

amplification of the fgfr1", "of the fgfr1 gene", "gene has been implicated", "has been implicated as", "been implicated as a", "implicated as a oncogenic", "as a oncogenic factor", "a oncogenic factor in", "oncogenic factor in a", "factor in a range", "in a range of", "a range of cancers", "of cancers including", "cancers including breast", "including breast ovarian", "lung oral squamous", "squamous carcinomas and", "carcinomas and rhabdomyosarcoma", "and rhabdomyosarcoma reviewed", "rhabdomyosarcoma reviewed in", "reviewed in turner and", "in turner and grose", "and grose 2010", "2011 although", "although there are other", "there are other candidate", "are other candidate genes", "other candidate genes in", "candidate genes in the", "genes in the amplified", "in the amplified region", "the amplified region and", "amplified region and the", "region and the definitive", "and the definitive role", "the definitive role of", "definitive role of fgfr1", "role of fgfr1 has", "of fgfr1 has not", "fgfr1 has not been", "has not been fully", "not been fully established.
more", "been fully established.
more recently", "established.
more recently fgfr1", "recently fgfr1 fusion", "fgfr1 fusion proteins have", "fusion proteins have been", "proteins have been identified", "been identified in a", "identified in a number", "a number of cancers", "of cancers these", "cancers these are", "these are thought to", "are thought to undergo", "thought to undergo constitutive", "to undergo constitutive ligand", "undergo constitutive ligand independent", "constitutive ligand independent dimerization", "ligand independent dimerization and", "independent dimerization and activation", "dimerization and activation based", "and activation based on", "activation based on dimerization", "based on dimerization motifs", "on dimerization motifs found", "dimerization motifs found in", "motifs found in the", "found in the fusion", "in the fusion partners", "fusion partners reviewed", "partners reviewed in", "in parker 2014", "parker 2014 .", "the fgfr1 gene has been", "fgfr1 gene has been shown", "gene has been shown to", "has been shown to be", "been shown to be subject", "shown to be subject to", "to be subject to activating", "be subject to activating mutations", "to activating mutations chromosomal", "activating mutations chromosomal rearrangements", "mutations chromosomal rearrangements and", "chromosomal rearrangements and gene amplification", "rearrangements and gene amplification leading", "and gene amplification leading to", "gene amplification leading to a", "amplification leading to a variety", "leading to a variety of", "to a variety of proliferative", "a variety of proliferative and", "variety of proliferative and developmental", "of proliferative and developmental disorders", "proliferative and developmental disorders depending", "and developmental disorders depending on", "developmental disorders depending on whether", "disorders depending on whether these", "depending on whether these events", "on whether these events occur", "whether these events occur in", "these events occur in the", "events occur in the germline", "occur in the germline or", "in the germline or arise", "the germline or arise somatically", "or arise somatically reviewed", "arise somatically reviewed in", "somatically reviewed in webster", "reviewed in webster and donoghue", "webster and donoghue 1997", "donoghue 1997 burke", "1997 burke 1998", "burke 1998 cunningham", "1998 cunningham 2007", "cunningham 2007 wesche", "2007 wesche 2011", "wesche 2011 greulich", "2011 greulich and pollock", "greulich and pollock 2011", "and pollock 2011 .", "2011 .


activating mutation", ".


activating mutation p252r", "


activating mutation p252r in fgfr1", "mutation p252r in fgfr1 is", "p252r in fgfr1 is associated", "in fgfr1 is associated with", "fgfr1 is associated with the", "is associated with the development", "associated with the development of", "with the development of pfeiffer", "the development of pfeiffer syndrome", "of pfeiffer syndrome characterized", "pfeiffer syndrome characterized by", "syndrome characterized by craniosynostosis", "characterized by craniosynostosis premature", "by craniosynostosis premature fusion", "craniosynostosis premature fusion of", "premature fusion of several sutures", "fusion of several sutures in", "of several sutures in the", "several sutures in the skull", "in the skull and", "the skull and broadened", "skull and broadened thumbs", "and broadened thumbs and toes", "thumbs and toes muenke", "toes muenke 1994", "muenke 1994 reviewed", "1994 reviewed in cunningham", "reviewed in cunningham 2007", "in cunningham 2007 .", "2007 . this residue", ". this residue falls", "this residue falls in a", "residue falls in a highly", "falls in a highly conserved", "in a highly conserved pro", "a highly conserved pro ser", "highly conserved pro ser dipeptide", "conserved pro ser dipeptide between", "pro ser dipeptide between the", "ser dipeptide between the second", "dipeptide between the second and", "between the second and third", "the second and third ig", "second and third ig domains", "and third ig domains of", "third ig domains of the", "ig domains of the extracellular", "domains of the extracellular region", "of the extracellular region of", "the extracellular region of the", "extracellular region of the receptor.", "region of the receptor. the", "of the receptor. the mutation", "the receptor. the mutation is", "receptor. the mutation is thought", "the mutation is thought to", "mutation is thought to increase", "is thought to increase the", "thought to increase the number", "to increase the number of", "increase the number of hydrogen", "the number of hydrogen bonds", "number of hydrogen bonds formed", "of hydrogen bonds formed with", "hydrogen bonds formed with the", "bonds formed with the ligand", "formed with the ligand and", "with the ligand and to", "the ligand and to thereby", "ligand and to thereby increase", "and to thereby increase ligand", "to thereby increase ligand binding", "thereby increase ligand binding affinity", "ligand binding affinity ibrahimi", "affinity ibrahimi 2004a", "ibrahimi 2004a . unlike", "2004a . unlike other fgf", ". unlike other fgf receptors", "other fgf receptors few", "fgf receptors few activating", "receptors few activating point", "few activating point mutations in", "activating point mutations in the", "point mutations in the fgfr1", "mutations in the fgfr1 coding", "in the fgfr1 coding sequence", "the fgfr1 coding sequence have", "fgfr1 coding sequence have been", "coding sequence have been identified", "sequence have been identified in", "have been identified in cancer.", "identified in cancer. point", "in cancer. point mutations", "cancer. point mutations in", "point mutations in the ig", "mutations in the ig ii", "in the ig ii iii", "the ig ii iii linker", "ig ii iii linker analagous", "ii iii linker analagous to", "iii linker analagous to the", "linker analagous to the p252r", "analagous to the p252r pfeiffer", "to the p252r pfeiffer syndrome", "the p252r pfeiffer syndrome mutation", "p252r pfeiffer syndrome mutation have", "pfeiffer syndrome mutation have been", "syndrome mutation have been identified", "mutation have been identified in", "have been identified in lung", "been identified in lung cancer", "identified in lung cancer and", "in lung cancer and melanoma", "cancer and melanoma ruhe", "melanoma ruhe 2007", "ruhe 2007 davies", "2007 davies 2005", "2005 and two", "and two kinase domain mutations", "two kinase domain mutations in", "kinase domain mutations in fgfr1", "domain mutations in fgfr1 have", "mutations in fgfr1 have been", "in fgfr1 have been identified", "fgfr1 have been identified in", "have been identified in glioblastoma", "identified in glioblastoma rand", "glioblastoma rand 2005", "rand 2005 network", "network tcga 2008 .

in", "tcga 2008 .

in contrast", ".

in contrast fgfr1", "contrast fgfr1 is", "fgfr1 is a target of", "is a target of chromosomal", "a target of chromosomal rearrangements", "target of chromosomal rearrangements in", "of chromosomal rearrangements in a", "chromosomal rearrangements in a number", "rearrangements in a number of", "in a number of cancers.", "number of cancers. fgfr1", "of cancers. fgfr1 has", "cancers. fgfr1 has been", "fgfr1 has been shown to", "been shown to be recurrently", "shown to be recurrently translocated", "to be recurrently translocated in", "be recurrently translocated in the", "recurrently translocated in the 8p11", "translocated in the 8p11 myeloproliferative", "in the 8p11 myeloproliferative syndrome", "8p11 myeloproliferative syndrome ems", "ems a pre", "a pre leukemic condition also", "pre leukemic condition also known", "leukemic condition also known as", "condition also known as stem", "also known as stem cell", "known as stem cell leukemia/lymphoma", "stem cell leukemia/lymphoma scll", "leukemia/lymphoma scll that", "scll that rapidly progresses", "that rapidly progresses to leukemia.", "progresses to leukemia. this", "to leukemia. this translocation", "leukemia. this translocation fuses", "this translocation fuses the kinase", "translocation fuses the kinase domain", "fuses the kinase domain of", "the kinase domain of fgfr1", "kinase domain of fgfr1 with", "domain of fgfr1 with the", "of fgfr1 with the dimerization", "fgfr1 with the dimerization domain", "with the dimerization domain of", "the dimerization domain of one", "dimerization domain of one of", "domain of one of 10", "of one of 10 identified", "one of 10 identified fusion", "of 10 identified fusion partners", "identified fusion partners resulting", "fusion partners resulting in", "partners resulting in the", "resulting in the constitutive dimerization", "in the constitutive dimerization and", "the constitutive dimerization and activation", "constitutive dimerization and activation of", "dimerization and activation of the", "and activation of the kinase", "of the kinase reviewed", "the kinase reviewed in", "kinase reviewed in jackson", "reviewed in jackson 2010", "in jackson 2010 .", "2010 .

amplification of", ".

amplification of the", "

amplification of the fgfr1 gene", "of the fgfr1 gene has", "fgfr1 gene has been implicated", "gene has been implicated as", "has been implicated as a", "been implicated as a oncogenic", "implicated as a oncogenic factor", "as a oncogenic factor in", "a oncogenic factor in a", "oncogenic factor in a range", "factor in a range of", "in a range of cancers", "range of cancers including", "of cancers including breast", "breast ovarian bladder", "ovarian bladder lung", "bladder lung oral", "lung oral squamous carcinomas", "oral squamous carcinomas and", "squamous carcinomas and rhabdomyosarcoma", "and rhabdomyosarcoma reviewed in", "rhabdomyosarcoma reviewed in turner", "reviewed in turner and grose", "turner and grose 2010", "grose 2010 wesche", "2010 wesche 2011", "2011 although there", "although there are other candidate", "there are other candidate genes", "are other candidate genes in", "other candidate genes in the", "candidate genes in the amplified", "genes in the amplified region", "in the amplified region and", "the amplified region and the", "amplified region and the definitive", "region and the definitive role", "and the definitive role of", "the definitive role of fgfr1", "definitive role of fgfr1 has", "role of fgfr1 has not", "of fgfr1 has not been", "fgfr1 has not been fully", "has not been fully established.
more", "not been fully established.
more recently", "fully established.
more recently fgfr1", "established.
more recently fgfr1 fusion", "recently fgfr1 fusion proteins", "fgfr1 fusion proteins have been", "fusion proteins have been identified", "proteins have been identified in", "have been identified in a", "been identified in a number", "identified in a number of", "in a number of cancers", "number of cancers these", "of cancers these are", "cancers these are thought", "these are thought to undergo", "are thought to undergo constitutive", "thought to undergo constitutive ligand", "to undergo constitutive ligand independent", "undergo constitutive ligand independent dimerization", "constitutive ligand independent dimerization and", "ligand independent dimerization and activation", "independent dimerization and activation based", "dimerization and activation based on", "and activation based on dimerization", "activation based on dimerization motifs", "based on dimerization motifs found", "on dimerization motifs found in", "dimerization motifs found in the", "motifs found in the fusion", "found in the fusion partners", "the fusion partners reviewed", "fusion partners reviewed in", "partners reviewed in parker", "reviewed in parker 2014", "in parker 2014 ." ] }, { "record_id": "GLY_000594_1_473", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5656169", "r hsa", "hsa 5656169", "r hsa 5656169" ] }, { "record_id": "GLY_000594_1_473", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "termination of", "of translesion", "translesion dna", "dna synthesis", "termination of translesion", "of translesion dna", "translesion dna synthesis", "termination of translesion dna", "of translesion dna synthesis", "termination of translesion dna synthesis", "the initiation", "initiation and", "and extent", "extent of", "has to", "to be", "be tightly", "tightly controlled", "controlled in", "in order", "order to", "to limit", "limit tls", "tls induced", "induced mutagenesis", "caused by", "by the", 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through", "in actin polymerization through binding", "actin polymerization through binding g", "polymerization through binding g actin", "through binding g actin and", "binding g actin and the", "g actin and the arp2/3", "the arp2/3 complex reviewed", "arp2/3 complex reviewed by", "complex reviewed by lane", "reviewed by lane et al.", "by lane et al. 2014", "lane et al. 2014 ." ] }, { "record_id": "GLY_000594_1_476", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5663220", "r hsa", "hsa 5663220", "r hsa 5663220" ] }, { "record_id": "GLY_000594_1_476", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate formins", "rho gtpases activate", "gtpases activate formins", "rho gtpases activate formins", "formins are", "are a", "a family", "family of", "of proteins", "proteins with", "with 15", "15 members", "members in", "in mammals", "organized into", "into 8", "8 subfamilies.", "subfamilies. formins", "are involved", "involved in", "in the", "the regulation", "regulation of", "of actin", "actin cytoskeleton.", "cytoskeleton. many", "many but", "but not", "not all", "all formin", "formin family", "family members", "members are", "are activated", "activated by", "by rho", "rho gtpases.", "gtpases. formins", "formins that", "that serve", "serve as", "as effectors", "effectors of", "of rho", "gtpases belong", "belong to", "to different", "different formin", "formin subfamilies", "subfamilies but", "but they", "they all", "all share", "share a", "a structural", "structural similarity", "similarity to", "to drosophila", "drosophila protein", "protein diaphanous", "diaphanous and", "and are", "are hence", "hence named", "named diaphanous", "diaphanous related", "related formins", "drfs .

drfs", ".

drfs activated", "gtpases contain", "contain a", "a gtpase", "gtpase binding", "binding domain", "at their", "their n", "n terminus", "followed by", "by formin", "formin homology", "homology domains", "domains 3", "and 2", "and a", "a diaphanous", "diaphanous autoregulatory", "autoregulatory domain", "at the", "the c", "c terminus.", "terminus. most", "most drfs", "drfs contain", "a dimerization", "dimerization domain", "a coiled", "coiled coil", "coil region", "in between", "between fh3", "fh3 and", "and fh1", "fh1 domains", "reviewed by", "by kuhn", "kuhn and", "and geyer", "geyer 2014", "2014 .", ". rho", "rho gtpase", "gtpase activated", "activated drfs", "drfs are", "are autoinhibited", "autoinhibited through", "through the", "the interaction", "interaction between", "and dad", "dad which", "which is", "is disrupted", "disrupted upon", "upon binding", "binding to", "to an", "an active", "active rho", "li and", "and higgs", "higgs 2003", "lammers et", "et al.", "al. 2005", "nezami et", "al. 2006", "2006 .", ". since", "since formins", "formins dimerize", "it is", "is not", "not clear", "clear whether", "whether the", "the fh3", "fh3 dad", "dad interaction", "interaction is", "is intra", "or intermolecular.", "intermolecular. fh2", "fh2 domain", "domain is", "is responsible", "responsible for", "for binding", "to the", "the f", "f actin", "actin and", "and contributes", "contributes to", "the formation", "formation of", "of head", "head to", "to tail", "tail formin", "formin dimers", "xu et", "al. 2004", "2004 .", ". the", "the proline", "proline rich", "rich fh1", "fh1 domain", "domain interacts", "interacts with", "with the", "the actin", "actin binding", "binding proteins", "proteins profilins", "thereby facilitating", "facilitating actin", "actin recruitment", "recruitment to", "to formins", "formins and", "and accelerating", "accelerating actin", "actin polymerization", "romero et", "kovar et", "2006 .

different", ".

different formins", "by different", "different rho", "gtpases in", "in different", "different cell", "cell contexts.", "contexts. fmnl1", "formin like", "like protein", "protein 1", "is activated", "by binding", "the rac1:gtp", "rac1:gtp and", "and is", "is involved", "of lamellipodia", "lamellipodia in", "in macrophages", "yayoshi yamamoto", "yamamoto et", "al. 2000", "of the", "the golgi", "golgi complex", "complex structure", "colon franco", "franco et", "al. 2011", "2011 .", ". activation", "activation of", "of fmnl1", "fmnl1 by", "by cdc42:gtp", "cdc42:gtp contributes", "the phagocytic", "phagocytic cup", "seth et", "of fmnl2", "protein 2", "and fmnl3", "protein 3", "by rhoc:gtp", "rhoc:gtp is", "in cancer", "cancer cell", "cell motility", "motility and", "and invasiveness", "kitzing et", "al. 2010", "vega et", ". diaph1", "by rhoa:gtp", "promotes elongation", "elongation of", "actin filaments", "filaments and", "and activation", "of srf", "srf mediated", "mediated transcription", "transcription which", "is inhibited", "inhibited by", "by unpolymerized", "unpolymerized actin", "miralles et", "al. 2003", "2003 .", ". rhof", "rhof mediated", "mediated activation", "of diaph1", "diaph1 is", "is implicated", "implicated in", "in formation", "of stress", "stress fibers", "fan et", "2010 .", "diaph1 and", "and diaph3", "diaph3 by", "by rhob:gtp", "rhob:gtp leads", "leads to", "to actin", "actin coat", "coat formation", "formation around", "around endosomes", "endosomes and", "and regulates", "regulates endosome", "endosome motility", "and trafficking", "fernandez borja", "borja et", "wallar et", "al. 2007", "2007 .", ". endosome", "endosome trafficking", "trafficking is", "is also", "also regulated", "regulated by", "by diaph2", "diaph2 transcription", "transcription isoform", "isoform 3", "diaph2 3", "upon activation", "activation by", "by rhod:gtp", "recruits src", "src kinase", "kinase to", "to endosomes", "tominaga et", "gasman et", ". diaph2", "isoform 2", "diaph2 2", "in mitosis", "mitosis where", "upon being", "being activated", "it facilitates", "facilitates the", "the capture", "capture of", "of astral", "astral microtubules", "microtubules by", "by kinetochores", "yasuda et", "cheng et", "diaph2 is", "in ovarian", "ovarian maintenance", "maintenance and", "and premature", "premature ovarian", "ovarian failure", "bione et", "al. 1998", "1998 .", ". daam1", "in linking", "linking wnt", "wnt signaling", "signaling to", "to cytoskeleton", "cytoskeleton reorganization", "habas et", "al. 2001", "2001 .", "formins are a", "are a family", "a family of", "family of proteins", "of proteins with", "proteins with 15", "with 15 members", "15 members in", "members in mammals", "mammals organized", "organized into 8", "into 8 subfamilies.", "8 subfamilies. formins", "subfamilies. formins are", "formins are involved", "are involved in", "involved in the", "in the regulation", "the regulation of", "regulation of actin", "of actin cytoskeleton.", "actin cytoskeleton. many", "cytoskeleton. many but", "many but not", "but not all", "not all formin", "all formin family", "formin family members", "family members are", "members are activated", "are activated by", "activated by rho", "by rho gtpases.", "rho gtpases. formins", "gtpases. formins that", "formins that serve", "that serve as", "serve as effectors", "as effectors of", "effectors of rho", "of rho gtpases", "rho gtpases belong", "gtpases belong to", "belong to different", "to different formin", "different formin subfamilies", "formin subfamilies but", "subfamilies but they", "but they all", "they all share", "all share a", "share a structural", "a structural similarity", "structural similarity to", "similarity to drosophila", "to drosophila protein", "drosophila protein diaphanous", "protein diaphanous and", "diaphanous and are", "and are hence", "are hence named", "hence named diaphanous", "named diaphanous related", "diaphanous related formins", "formins drfs", "drfs .

drfs activated", ".

drfs activated by", "by rho gtpases", "rho gtpases contain", "gtpases contain a", "contain a gtpase", "a gtpase binding", "gtpase binding domain", "domain gbd", "gbd at", "at their n", "their n terminus", "terminus followed", "followed by formin", "by formin homology", "formin homology domains", "homology domains 3", "3 1", "1 and", "2 fh3", "fh3 fh1", "fh1 fh2", "fh2 and", "and a diaphanous", "a diaphanous autoregulatory", "diaphanous autoregulatory domain", "domain dad", "dad at", "at the c", "the c terminus.", "c terminus. most", "terminus. most drfs", "most drfs contain", "drfs contain a", "contain a dimerization", "a dimerization domain", "domain dd", "dd and", "and a coiled", "a coiled coil", "coiled coil region", "region cc", "cc in", "in between fh3", "between fh3 and", "fh3 and fh1", "and fh1 domains", "domains reviewed", "reviewed by kuhn", "by kuhn and", "kuhn and geyer", "and geyer 2014", "geyer 2014 .", "2014 . rho", ". rho gtpase", "rho gtpase activated", "gtpase activated drfs", "activated drfs are", "drfs are autoinhibited", "are autoinhibited through", "autoinhibited through the", "through the interaction", "the interaction between", "interaction between fh3", "fh3 and dad", "and dad which", "dad which is", "which is disrupted", "is disrupted upon", "disrupted upon binding", "upon binding to", "binding to an", "to an active", "an active rho", "active rho gtpase", "gtpase li", "li and higgs", "and higgs 2003", "2003 lammers", "lammers et al.", "et al. 2005", "2005 nezami", "nezami et al.", "et al. 2006", "al. 2006 .", "2006 . since", ". since formins", "since formins dimerize", "dimerize it", "it is not", "is not clear", "not clear whether", "clear whether the", "whether the fh3", "the fh3 dad", "fh3 dad interaction", "dad interaction is", "interaction is intra", "intra or", "or intermolecular. fh2", "intermolecular. fh2 domain", "fh2 domain is", "domain is responsible", "is responsible for", "responsible for binding", "for binding to", "binding to the", "to the f", "the f actin", "f actin and", "actin and contributes", "and contributes to", "contributes to the", "to the formation", "the formation of", "formation of head", "of head to", "head to tail", "to tail formin", "tail formin dimers", "dimers xu", "xu et al.", "et al. 2004", "al. 2004 .", "2004 . the", ". the proline", "the proline rich", "proline rich fh1", "rich fh1 domain", "fh1 domain interacts", "domain interacts with", "interacts with the", "with the actin", "the actin binding", "actin binding proteins", "binding proteins profilins", "profilins thereby", "thereby facilitating actin", "facilitating actin recruitment", "actin recruitment to", "recruitment to formins", "to formins and", "formins and accelerating", "and accelerating actin", "accelerating actin polymerization", "polymerization romero", "romero et al.", "2004 kovar", "kovar et al.", "al. 2006 .

different", "2006 .

different formins", ".

different formins are", "formins are activated", "activated by different", "by different rho", "different rho gtpases", "rho gtpases in", "gtpases in different", "in different cell", "different cell contexts.", "cell contexts. fmnl1", "fmnl1 formin", "formin like protein", "like protein 1", "1 is", "is activated by", "activated by binding", "by binding to", "to the rac1:gtp", "the rac1:gtp and", "rac1:gtp and is", "and is involved", "is involved in", "in the formation", "formation of lamellipodia", "of lamellipodia in", "lamellipodia in macrophages", "macrophages yayoshi", "yayoshi yamamoto et", "yamamoto et al.", "et al. 2000", "2000 and", "regulation of the", "of the golgi", "the golgi complex", "golgi complex structure", "structure colon", "colon franco et", "franco et al.", "et al. 2011", "al. 2011 .", "2011 . activation", ". activation of", "activation of fmnl1", "of fmnl1 by", "fmnl1 by cdc42:gtp", "by cdc42:gtp contributes", "cdc42:gtp contributes to", "formation of the", "of the phagocytic", "the phagocytic cup", "cup seth", "seth et al.", "2006 . activation", "activation of fmnl2", "fmnl2 formin", "like protein 2", "2 and", "fmnl3 formin", "like protein 3", "3 by", "by rhoc:gtp is", "rhoc:gtp is involved", "involved in cancer", "in cancer cell", "cancer cell motility", "cell motility and", "motility and invasiveness", "invasiveness kitzing", "kitzing et al.", "et al. 2010", "2010 vega", "vega et al.", "2011 . diaph1", "diaph1 activated", "activated by rhoa:gtp", "rhoa:gtp promotes", "promotes elongation of", "elongation of actin", "of actin filaments", "actin filaments and", "filaments and activation", "and activation of", "activation of srf", "of srf mediated", "srf mediated transcription", "mediated transcription which", "transcription which is", "which is inhibited", "is inhibited by", "inhibited by unpolymerized", "by unpolymerized actin", "actin miralles", "miralles et al.", "et al. 2003", "al. 2003 .", "2003 . rhof", ". rhof mediated", "rhof mediated activation", "mediated activation of", "activation of diaph1", "of diaph1 is", "diaph1 is implicated", "is implicated in", "implicated in formation", "in formation of", "formation of stress", "of stress fibers", "fibers fan", "fan et al.", "al. 2010 .", "2010 . activation", "of diaph1 and", "diaph1 and diaph3", "and diaph3 by", "diaph3 by rhob:gtp", "by rhob:gtp leads", "rhob:gtp leads to", "leads to actin", "to actin coat", "actin coat formation", "coat formation around", "formation around endosomes", "around endosomes and", "endosomes and regulates", "and regulates endosome", "regulates endosome motility", "endosome motility and", "motility and trafficking", "trafficking fernandez", "fernandez borja et", "borja et al.", "2005 wallar", "wallar et al.", "et al. 2007", "al. 2007 .", "2007 . endosome", ". endosome trafficking", "endosome trafficking is", "trafficking is also", "is also regulated", "also regulated by", "regulated by diaph2", "by diaph2 transcription", "diaph2 transcription isoform", "transcription isoform 3", "3 diaph2", "3 which", "which upon", "upon activation by", "activation by rhod:gtp", "rhod:gtp recruits", "recruits src kinase", "src kinase to", "kinase to endosomes", "endosomes tominaga", "tominaga et al.", "2000 gasman", "gasman et al.", "2003 . diaph2", ". diaph2 transcription", "transcription isoform 2", "2 diaph2", "2 is", "involved in mitosis", "in mitosis where", "where upon", "upon being activated", "being activated by", "activated by cdc42:gtp", "cdc42:gtp it", "it facilitates the", "facilitates the capture", "the capture of", "capture of astral", "of astral microtubules", "astral microtubules by", "microtubules by kinetochores", "kinetochores yasuda", "yasuda et al.", "2004 cheng", "cheng et al.", "2011 . diaph2", ". diaph2 is", "diaph2 is implicated", "implicated in ovarian", "in ovarian maintenance", "ovarian maintenance and", "maintenance and premature", "and premature ovarian", "premature ovarian failure", "failure bione", "bione et al.", "et al. 1998", "al. 1998 .", "1998 . daam1", "daam1 activated", "rhoa:gtp is", "involved in linking", "in linking wnt", "linking wnt signaling", "wnt signaling to", "signaling to cytoskeleton", "to cytoskeleton reorganization", "reorganization habas", "habas et al.", "et al. 2001", "al. 2001 .", "formins are a family", "are a family of", "a family of proteins", "family of proteins with", "of proteins with 15", "proteins with 15 members", "with 15 members in", "15 members in mammals", "in mammals organized", "mammals organized into", "organized into 8 subfamilies.", "into 8 subfamilies. formins", "8 subfamilies. formins are", "subfamilies. formins are involved", "formins are involved in", "are involved in the", "involved in the regulation", "in the regulation of", "the regulation of actin", "regulation of actin cytoskeleton.", "of actin cytoskeleton. many", "actin cytoskeleton. many but", "cytoskeleton. many but not", "many but not all", "but not all formin", "not all formin family", "all formin family members", "formin family members are", "family members are activated", "members are activated by", "are activated by rho", "activated by rho gtpases.", "by rho gtpases. formins", "rho gtpases. formins that", "gtpases. formins that serve", "formins that serve as", "that serve as effectors", "serve as effectors of", "as effectors of rho", "effectors of rho gtpases", "of rho gtpases belong", "rho gtpases belong to", "gtpases belong to different", "belong to different formin", "to different formin subfamilies", "different formin subfamilies but", "formin subfamilies but they", "subfamilies but they all", "but they all share", "they all share a", "all share a structural", "share a structural similarity", "a structural similarity to", "structural similarity to drosophila", "similarity to drosophila protein", "to drosophila protein diaphanous", "drosophila protein diaphanous and", "protein diaphanous and are", "diaphanous and are hence", "and are hence named", "are hence named diaphanous", "hence named diaphanous related", "named diaphanous related formins", "related formins drfs", "formins drfs .

drfs", "drfs .

drfs activated by", ".

drfs activated by rho", "activated by rho gtpases", "by rho gtpases contain", "rho gtpases contain a", "gtpases contain a gtpase", "contain a gtpase binding", "a gtpase binding domain", "binding domain gbd", "gbd at their", "at their n terminus", "n terminus followed", "terminus followed by", "followed by formin homology", "by formin homology domains", "formin homology domains 3", "domains 3 1", "1 and 2", "and 2 fh3", "fh2 and a", "and a diaphanous autoregulatory", "a diaphanous autoregulatory domain", "autoregulatory domain dad", "dad at the", "at the c terminus.", "the c terminus. most", "c terminus. most drfs", "terminus. most drfs contain", "most drfs contain a", "drfs contain a dimerization", "contain a dimerization domain", "dimerization domain dd", "dd and a", "and a coiled coil", "a coiled coil region", "coil region cc", "cc in between", "in between fh3 and", "between fh3 and fh1", "fh3 and fh1 domains", "fh1 domains reviewed", "domains reviewed by", "reviewed by kuhn and", "by kuhn and geyer", "kuhn and geyer 2014", "and geyer 2014 .", "geyer 2014 . rho", "2014 . rho gtpase", ". rho gtpase activated", "rho gtpase activated drfs", "gtpase activated drfs are", "activated drfs are autoinhibited", "drfs are autoinhibited through", "are autoinhibited through the", "autoinhibited through the interaction", "through the interaction between", "the interaction between fh3", "interaction between fh3 and", "between fh3 and dad", "fh3 and dad which", "and dad which is", "dad which is disrupted", "which is disrupted upon", "is disrupted upon binding", "disrupted upon binding to", "upon binding to an", "binding to an active", "to an active rho", "an active rho gtpase", "rho gtpase li", "gtpase li and", "li and higgs 2003", "higgs 2003 lammers", "2003 lammers et", "lammers et al. 2005", "al. 2005 nezami", "2005 nezami et", "nezami et al. 2006", "et al. 2006 .", "al. 2006 . since", "2006 . since formins", ". since formins dimerize", "formins dimerize it", "dimerize it is", "it is not clear", "is not clear whether", "not clear whether the", "clear whether the fh3", "whether the fh3 dad", "the fh3 dad interaction", "fh3 dad interaction is", "dad interaction is intra", "is intra or", "intra or intermolecular.", "or intermolecular. fh2 domain", "intermolecular. fh2 domain is", "fh2 domain is responsible", "domain is responsible for", "is responsible for binding", "responsible for binding to", "for binding to the", "binding to the f", "to the f actin", "the f actin and", "f actin and contributes", "actin and contributes to", "and contributes to the", "contributes to the formation", "to the formation of", "the formation of head", "formation of head to", "of head to tail", "head to tail formin", "to tail formin dimers", "formin dimers xu", "dimers xu et", "xu et al. 2004", "et al. 2004 .", "al. 2004 . the", "2004 . the proline", ". the proline rich", "the proline rich fh1", "proline rich fh1 domain", "rich fh1 domain interacts", "fh1 domain interacts with", "domain interacts with the", "interacts with the actin", "with the actin binding", "the actin binding proteins", "actin binding proteins profilins", "proteins profilins thereby", "profilins thereby facilitating", "thereby facilitating actin recruitment", "facilitating actin recruitment to", "actin recruitment to formins", "recruitment to formins and", "to formins and accelerating", "formins and accelerating actin", "and accelerating actin polymerization", "actin polymerization romero", "polymerization romero et", "romero et al. 2004", "al. 2004 kovar", "2004 kovar et", "kovar et al. 2006", "et al. 2006 .

different", "al. 2006 .

different formins", "2006 .

different formins are", ".

different formins are activated", "formins are activated by", "are activated by different", "activated by different rho", "by different rho gtpases", "different rho gtpases in", "rho gtpases in different", "gtpases in different cell", "in different cell contexts.", "different cell contexts. fmnl1", "contexts. fmnl1 formin", "fmnl1 formin like", "formin like protein 1", "protein 1 is", "1 is activated", "is activated by binding", "activated by binding to", "by binding to the", "binding to the rac1:gtp", "to the rac1:gtp and", "the rac1:gtp and is", "rac1:gtp and is involved", "and is involved in", "is involved in the", "involved in the formation", "in the formation of", "the formation of lamellipodia", "formation of lamellipodia in", "of lamellipodia in macrophages", "in macrophages yayoshi", "macrophages yayoshi yamamoto", "yayoshi yamamoto et al.", "yamamoto et al. 2000", "al. 2000 and", "2000 and is", "the regulation of the", "regulation of the golgi", "of the golgi complex", "the golgi complex structure", "complex structure colon", "structure colon franco", "colon franco et al.", "franco et al. 2011", "et al. 2011 .", "al. 2011 . activation", "2011 . activation of", ". activation of fmnl1", "activation of fmnl1 by", "of fmnl1 by cdc42:gtp", "fmnl1 by cdc42:gtp contributes", "by cdc42:gtp contributes to", "cdc42:gtp contributes to the", "the formation of the", "formation of the phagocytic", "of the phagocytic cup", "phagocytic cup seth", "cup seth et", "seth et al. 2006", "al. 2006 . activation", "2006 . activation of", ". activation of fmnl2", "of fmnl2 formin", "fmnl2 formin like", "formin like protein 2", "protein 2 and", "2 and fmnl3", "and fmnl3 formin", "fmnl3 formin like", "formin like protein 3", "protein 3 by", "3 by rhoc:gtp", "by rhoc:gtp is involved", "rhoc:gtp is involved in", "is involved in cancer", "involved in cancer cell", "in cancer cell motility", "cancer cell motility and", "cell motility and invasiveness", "and invasiveness kitzing", "invasiveness kitzing et", "kitzing et al. 2010", "al. 2010 vega", "2010 vega et", "vega et al. 2011", "al. 2011 . diaph1", ". diaph1 activated", "diaph1 activated by", "by rhoa:gtp promotes", "rhoa:gtp promotes elongation", "promotes elongation of actin", "elongation of actin filaments", "of actin filaments and", "actin filaments and activation", "filaments and activation of", "and activation of srf", "activation of srf mediated", "of srf mediated transcription", "srf mediated transcription which", "mediated transcription which is", "transcription which is inhibited", "which is inhibited by", "is inhibited by unpolymerized", "inhibited by unpolymerized actin", "unpolymerized actin miralles", "actin miralles et", "miralles et al. 2003", "et al. 2003 .", "al. 2003 . rhof", "2003 . rhof mediated", ". rhof mediated activation", "rhof mediated activation of", "mediated activation of diaph1", "activation of diaph1 is", "of diaph1 is implicated", "diaph1 is implicated in", "is implicated in formation", "implicated in formation of", "in formation of stress", "formation of stress fibers", "stress fibers fan", "fibers fan et", "fan et al. 2010", "et al. 2010 .", "al. 2010 . activation", "2010 . activation of", ". activation of diaph1", "activation of diaph1 and", "of diaph1 and diaph3", "diaph1 and diaph3 by", "and diaph3 by rhob:gtp", "diaph3 by rhob:gtp leads", "by rhob:gtp leads to", "rhob:gtp leads to actin", "leads to actin coat", "to actin coat formation", "actin coat formation around", "coat formation around endosomes", "formation around endosomes and", "around endosomes and regulates", "endosomes and regulates endosome", "and regulates endosome motility", "regulates endosome motility and", "endosome motility and trafficking", "and trafficking fernandez", "trafficking fernandez borja", "fernandez borja et al.", "borja et al. 2005", "al. 2005 wallar", "2005 wallar et", "wallar et al. 2007", "et al. 2007 .", "al. 2007 . endosome", "2007 . endosome trafficking", ". endosome trafficking is", "endosome trafficking is also", "trafficking is also regulated", "is also regulated by", "also regulated by diaph2", "regulated by diaph2 transcription", "by diaph2 transcription isoform", "diaph2 transcription isoform 3", "isoform 3 diaph2", "3 diaph2 3", "diaph2 3 which", "which upon activation", "upon activation by rhod:gtp", "by rhod:gtp recruits", "rhod:gtp recruits src", "recruits src kinase to", "src kinase to endosomes", "to endosomes tominaga", "endosomes tominaga et", "tominaga et al. 2000", "al. 2000 gasman", "2000 gasman et", "gasman et al. 2003", "al. 2003 . diaph2", "2003 . diaph2 transcription", ". diaph2 transcription isoform", "diaph2 transcription isoform 2", "isoform 2 diaph2", "2 diaph2 2", "diaph2 2 is", "2 is involved", "is involved in mitosis", "involved in mitosis where", "mitosis where upon", "where upon being", "upon being activated by", "being activated by cdc42:gtp", "by cdc42:gtp it", "cdc42:gtp it facilitates", "it facilitates the capture", "facilitates the capture of", "the capture of astral", "capture of astral microtubules", "of astral microtubules by", "astral microtubules by kinetochores", "by kinetochores yasuda", "kinetochores yasuda et", "yasuda et al. 2004", "al. 2004 cheng", "2004 cheng et", "cheng et al. 2011", "al. 2011 . diaph2", "2011 . diaph2 is", ". diaph2 is implicated", "diaph2 is implicated in", "is implicated in ovarian", "implicated in ovarian maintenance", "in ovarian maintenance and", "ovarian maintenance and premature", "maintenance and premature ovarian", "and premature ovarian failure", "ovarian failure bione", "failure bione et", "bione et al. 1998", "et al. 1998 .", "al. 1998 . daam1", ". daam1 activated", "daam1 activated by", "by rhoa:gtp is", "rhoa:gtp is involved", "is involved in linking", "involved in linking wnt", "in linking wnt signaling", "linking wnt signaling to", "wnt signaling to cytoskeleton", "signaling to cytoskeleton reorganization", "cytoskeleton reorganization habas", "reorganization habas et", "habas et al. 2001", "et al. 2001 .", "formins are a family of", "are a family of proteins", "a family of proteins with", "family of proteins with 15", "of proteins with 15 members", "proteins with 15 members in", "with 15 members in mammals", "members in mammals organized", "in mammals organized into", "mammals organized into 8", "organized into 8 subfamilies. formins", "into 8 subfamilies. formins are", "8 subfamilies. formins are involved", "subfamilies. formins are involved in", "formins are involved in the", "are involved in the regulation", "involved in the regulation of", "in the regulation of actin", "the regulation of actin cytoskeleton.", "regulation of actin cytoskeleton. many", "of actin cytoskeleton. many but", "actin cytoskeleton. many but not", "cytoskeleton. many but not all", "many but not all formin", "but not all formin family", "not all formin family members", "all formin family members are", "formin family members are activated", "family members are activated by", "members are activated by rho", "are activated by rho gtpases.", "activated by rho gtpases. formins", "by rho gtpases. formins that", "rho gtpases. formins that serve", "gtpases. formins that serve as", "formins that serve as effectors", "that serve as effectors of", "serve as effectors of rho", "as effectors of rho gtpases", "effectors of rho gtpases belong", "of rho gtpases belong to", "rho gtpases belong to different", "gtpases belong to different formin", "belong to different formin subfamilies", "to different formin subfamilies but", "different formin subfamilies but they", "formin subfamilies but they all", "subfamilies but they all share", "but they all share a", "they all share a structural", "all share a structural similarity", "share a structural similarity to", "a structural similarity to drosophila", "structural similarity to drosophila protein", "similarity to drosophila protein diaphanous", "to drosophila protein diaphanous and", "drosophila protein diaphanous and are", "protein diaphanous and are hence", "diaphanous and are hence named", "and are hence named diaphanous", "are hence named diaphanous related", "hence named diaphanous related formins", "diaphanous related formins drfs", "related formins drfs .

drfs", "formins drfs .

drfs activated", "drfs .

drfs activated by rho", ".

drfs activated by rho gtpases", "activated by rho gtpases contain", "by rho gtpases contain a", "rho gtpases contain a gtpase", "gtpases contain a gtpase binding", "contain a gtpase binding domain", "gtpase binding domain gbd", "domain gbd at", "gbd at their n", "their n terminus followed", "n terminus followed by", "terminus followed by formin", "followed by formin homology domains", "by formin homology domains 3", "homology domains 3 1", "3 1 and", "2 fh3 fh1", "fh3 fh1 fh2", "fh1 fh2 and", "fh2 and a diaphanous", "and a diaphanous autoregulatory domain", "diaphanous autoregulatory domain dad", "domain dad at", "dad at the c", "at the c terminus. most", "the c terminus. most drfs", "c terminus. most drfs contain", "terminus. most drfs contain a", "most drfs contain a dimerization", "drfs contain a dimerization domain", "a dimerization domain dd", "domain dd and", "dd and a coiled", "and a coiled coil region", "coiled coil region cc", "region cc in", "cc in between fh3", "in between fh3 and fh1", "between fh3 and fh1 domains", "and fh1 domains reviewed", "fh1 domains reviewed by", "domains reviewed by kuhn", "reviewed by kuhn and geyer", "by kuhn and geyer 2014", "kuhn and geyer 2014 .", "and geyer 2014 . rho", "geyer 2014 . rho gtpase", "2014 . rho gtpase activated", ". rho gtpase activated drfs", "rho gtpase activated drfs are", "gtpase activated drfs are autoinhibited", "activated drfs are autoinhibited through", "drfs are autoinhibited through the", "are autoinhibited through the interaction", "autoinhibited through the interaction between", "through the interaction between fh3", "the interaction between fh3 and", "interaction between fh3 and dad", "between fh3 and dad which", "fh3 and dad which is", "and dad which is disrupted", "dad which is disrupted upon", "which is disrupted upon binding", "is disrupted upon binding to", "disrupted upon binding to an", "upon binding to an active", "binding to an active rho", "to an active rho gtpase", "active rho gtpase li", "rho gtpase li and", "gtpase li and higgs", "and higgs 2003 lammers", "higgs 2003 lammers et", "2003 lammers et al.", "et al. 2005 nezami", "al. 2005 nezami et", "2005 nezami et al.", "nezami et al. 2006 .", "et al. 2006 . since", "al. 2006 . since formins", "2006 . since formins dimerize", "since formins dimerize it", "formins dimerize it is", "dimerize it is not", "it is not clear whether", "is not clear whether the", "not clear whether the fh3", "clear whether the fh3 dad", "whether the fh3 dad interaction", "the fh3 dad interaction is", "fh3 dad interaction is intra", "interaction is intra or", "is intra or intermolecular.", "intra or intermolecular. fh2", "or intermolecular. fh2 domain is", "intermolecular. fh2 domain is responsible", "fh2 domain is responsible for", "domain is responsible for binding", "is responsible for binding to", "responsible for binding to the", "for binding to the f", "binding to the f actin", "to the f actin and", "the f actin and contributes", "f actin and contributes to", "actin and contributes to the", "and contributes to the formation", "contributes to the formation of", "to the formation of head", "the formation of head to", "formation of head to tail", "of head to tail formin", "head to tail formin dimers", "tail formin dimers xu", "formin dimers xu et", "dimers xu et al.", "xu et al. 2004 .", "et al. 2004 . the", "al. 2004 . the proline", "2004 . the proline rich", ". the proline rich fh1", "the proline rich fh1 domain", "proline rich fh1 domain interacts", "rich fh1 domain interacts with", "fh1 domain interacts with the", "domain interacts with the actin", "interacts with the actin binding", "with the actin binding proteins", "the actin binding proteins profilins", "binding proteins profilins thereby", "proteins profilins thereby facilitating", "profilins thereby facilitating actin", "thereby facilitating actin recruitment to", "facilitating actin recruitment to formins", "actin recruitment to formins and", "recruitment to formins and accelerating", "to formins and accelerating actin", "formins and accelerating actin polymerization", "accelerating actin polymerization romero", "actin polymerization romero et", "polymerization romero et al.", "et al. 2004 kovar", "al. 2004 kovar et", "2004 kovar et al.", "kovar et al. 2006 .

different", "et al. 2006 .

different formins", "al. 2006 .

different formins are", "2006 .

different formins are activated", ".

different formins are activated by", "formins are activated by different", "are activated by different rho", "activated by different rho gtpases", "by different rho gtpases in", "different rho gtpases in different", "rho gtpases in different cell", "gtpases in different cell contexts.", "in different cell contexts. fmnl1", "cell contexts. fmnl1 formin", "contexts. fmnl1 formin like", "fmnl1 formin like protein", "like protein 1 is", "protein 1 is activated", "1 is activated by", "is activated by binding to", "activated by binding to the", "by binding to the rac1:gtp", "binding to the rac1:gtp and", "to the rac1:gtp and is", "the rac1:gtp and is involved", "rac1:gtp and is involved in", "and is involved in the", "is involved in the formation", "involved in the formation of", "in the formation of lamellipodia", "the formation of lamellipodia in", "formation of lamellipodia in macrophages", "lamellipodia in macrophages yayoshi", "in macrophages yayoshi yamamoto", "macrophages yayoshi yamamoto et", "yayoshi yamamoto et al. 2000", "et al. 2000 and", "al. 2000 and is", "2000 and is involved", "is involved in the regulation", "in the regulation of the", "the regulation of the golgi", "regulation of the golgi complex", "of the golgi complex structure", "golgi complex structure colon", "complex structure colon franco", "structure colon franco et", "colon franco et al. 2011", "franco et al. 2011 .", "et al. 2011 . activation", "al. 2011 . activation of", "2011 . activation of fmnl1", ". activation of fmnl1 by", "activation of fmnl1 by cdc42:gtp", "of fmnl1 by cdc42:gtp contributes", "fmnl1 by cdc42:gtp contributes to", "by cdc42:gtp contributes to the", "cdc42:gtp contributes to the formation", "to the formation of the", "the formation of the phagocytic", "formation of the phagocytic cup", "the phagocytic cup seth", "phagocytic cup seth et", "cup seth et al.", "seth et al. 2006 .", "et al. 2006 . activation", "al. 2006 . activation of", "2006 . activation of fmnl2", "activation of fmnl2 formin", "of fmnl2 formin like", "fmnl2 formin like protein", "like protein 2 and", "protein 2 and fmnl3", "and fmnl3 formin like", "fmnl3 formin like protein", "like protein 3 by", "protein 3 by rhoc:gtp", "3 by rhoc:gtp is", "by rhoc:gtp is involved in", "rhoc:gtp is involved in cancer", "is involved in cancer cell", "involved in cancer cell motility", "in cancer cell motility and", "cancer cell motility and invasiveness", "motility and invasiveness kitzing", "and invasiveness kitzing et", "invasiveness kitzing et al.", "et al. 2010 vega", "al. 2010 vega et", "2010 vega et al.", "vega et al. 2011 .", "et al. 2011 . diaph1", "2011 . diaph1 activated", ". diaph1 activated by", "diaph1 activated by rhoa:gtp", "activated by rhoa:gtp promotes", "by rhoa:gtp promotes elongation", "rhoa:gtp promotes elongation of", "promotes elongation of actin filaments", "elongation of actin filaments and", "of actin filaments and activation", "actin filaments and activation of", "filaments and activation of srf", "and activation of srf mediated", "activation of srf mediated transcription", "of srf mediated transcription which", "srf mediated transcription which is", "mediated transcription which is inhibited", "transcription which is inhibited by", "which is inhibited by unpolymerized", "is inhibited by unpolymerized actin", "by unpolymerized actin miralles", "unpolymerized actin miralles et", "actin miralles et al.", "miralles et al. 2003 .", "et al. 2003 . rhof", "al. 2003 . rhof mediated", "2003 . rhof mediated activation", ". rhof mediated activation of", "rhof mediated activation of diaph1", "mediated activation of diaph1 is", "activation of diaph1 is implicated", "of diaph1 is implicated in", "diaph1 is implicated in formation", "is implicated in formation of", "implicated in formation of stress", "in formation of stress fibers", "of stress fibers fan", "stress fibers fan et", "fibers fan et al.", "fan et al. 2010 .", "et al. 2010 . activation", "al. 2010 . activation of", "2010 . activation of diaph1", ". activation of diaph1 and", "activation of diaph1 and diaph3", "of diaph1 and diaph3 by", "diaph1 and diaph3 by rhob:gtp", "and diaph3 by rhob:gtp leads", "diaph3 by rhob:gtp leads to", "by rhob:gtp leads to actin", "rhob:gtp leads to actin coat", "leads to actin coat formation", "to actin coat formation around", "actin coat formation around endosomes", "coat formation around endosomes and", "formation around endosomes and regulates", "around endosomes and regulates endosome", "endosomes and regulates endosome motility", "and regulates endosome motility and", "regulates endosome motility and trafficking", "motility and trafficking fernandez", "and trafficking fernandez borja", "trafficking fernandez borja et", "fernandez borja et al. 2005", "et al. 2005 wallar", "al. 2005 wallar et", "2005 wallar et al.", "wallar et al. 2007 .", "et al. 2007 . endosome", "al. 2007 . endosome trafficking", "2007 . endosome trafficking is", ". endosome trafficking is also", "endosome trafficking is also regulated", "trafficking is also regulated by", "is also regulated by diaph2", "also regulated by diaph2 transcription", "regulated by diaph2 transcription isoform", "by diaph2 transcription isoform 3", "transcription isoform 3 diaph2", "isoform 3 diaph2 3", "3 which upon", "which upon activation by", "activation by rhod:gtp recruits", "by rhod:gtp recruits src", "rhod:gtp recruits src kinase", "recruits src kinase to endosomes", "kinase to endosomes tominaga", "to endosomes tominaga et", "endosomes tominaga et al.", "et al. 2000 gasman", "al. 2000 gasman et", "2000 gasman et al.", "gasman et al. 2003 .", "et al. 2003 . diaph2", "al. 2003 . diaph2 transcription", "2003 . diaph2 transcription isoform", ". diaph2 transcription isoform 2", "transcription isoform 2 diaph2", "isoform 2 diaph2 2", "diaph2 2 is involved", "2 is involved in", "is involved in mitosis where", "in mitosis where upon", "mitosis where upon being", "where upon being activated", "upon being activated by cdc42:gtp", "activated by cdc42:gtp it", "by cdc42:gtp it facilitates", "cdc42:gtp it facilitates the", "it facilitates the capture of", "facilitates the capture of astral", "the capture of astral microtubules", "capture of astral microtubules by", "of astral microtubules by kinetochores", "microtubules by kinetochores yasuda", "by kinetochores yasuda et", "kinetochores yasuda et al.", "et al. 2004 cheng", "al. 2004 cheng et", "2004 cheng et al.", "cheng et al. 2011 .", "et al. 2011 . diaph2", "al. 2011 . diaph2 is", "2011 . diaph2 is implicated", ". diaph2 is implicated in", "diaph2 is implicated in ovarian", "is implicated in ovarian maintenance", "implicated in ovarian maintenance and", "in ovarian maintenance and premature", "ovarian maintenance and premature ovarian", "maintenance and premature ovarian failure", "premature ovarian failure bione", "ovarian failure bione et", "failure bione et al.", "bione et al. 1998 .", "et al. 1998 . daam1", "1998 . daam1 activated", ". daam1 activated by", "daam1 activated by rhoa:gtp", "activated by rhoa:gtp is", "by rhoa:gtp is involved", "rhoa:gtp is involved in", "is involved in linking wnt", "involved in linking wnt signaling", "in linking wnt signaling to", "linking wnt signaling to cytoskeleton", "wnt signaling to cytoskeleton reorganization", "to cytoskeleton reorganization habas", "cytoskeleton reorganization habas et", "reorganization habas et al.", "habas et al. 2001 ." ] }, { "record_id": "GLY_000594_1_477", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5666185", "r hsa", "hsa 5666185", "r hsa 5666185" ] }, { "record_id": "GLY_000594_1_477", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate rhotekin", "rhotekin and", "and rhophilins", "rho gtpases activate", "gtpases activate rhotekin", "activate rhotekin and", "rhotekin and rhophilins", "rho gtpases activate rhotekin", "gtpases activate rhotekin and", "activate rhotekin and rhophilins", "rho gtpases activate rhotekin and", "gtpases activate rhotekin and rhophilins", "is a", "a protein", "protein with", "with an", "an n", "n terminally", "terminally located", "located rho", "rho gtpase", "gtpase binding", "binding domain", "that shares", "shares a", "a limited", "limited sequence", "sequence homology", "homology with", "with pkns", "pkns and", "and rhophilins.", "rhophilins. rtkn", "rtkn binds", "binds to", "to gtp", "gtp bound", "bound rhoa", "rhob and", "and rhoc", "rhoc and", "and can", "can inhibit", "inhibit their", "their gtpase", "gtpase activity", "reid et", "et al.", "al. 1996", "fu et", "al. 2000", "which can", "can be", "be corroborated", "corroborated by", "by protein", "protein kinase", "kinase d", "d mediated", "mediated phosphorylation", "phosphorylation of", "of rtkn", "pusapati et", "al. 2012", "2012 .", ". rtkn", "rtkn is", "is implicated", "implicated in", "in the", "the establishment", "establishment of", "of cell", "cell polarity", "sudo et", "al. 2006", "septin organization", "ito et", "al. 2005", "al. 2007", "and stimulation", "stimulation of", "of srf", "srf mediated", "mediated transcription", "reynaud et", "2000 .", "rtkn can", "can have", "have an", "an anti", "anti apoptotic", "apoptotic effect", "effect that", "that depends", "depends on", "on the", "the activation", "activation of", "of nfkb", "nf kappab", "liu et", "al. 2004", "2004 .", ". rtkn2", "rhotekin 2", "is another", "another rhotekin", "rhotekin exclusively", "exclusively expressed", "expressed in", "in lymphocytes", "collier et", ". the", "the function", "function and", "and the", "the mechanism", "mechanism of", "of action", "action of", "of rtkn2", "rtkn2 are", "are unknown.

rhophillins", "unknown.

rhophillins include", "include two", "two family", "family members", "rhophilin 1", "and rhophilin", "rhophilin 2", "with ~75%", "~75% sequence", "sequence identity.", "identity. a", "a rho", "domain is", "is located", "located at", "at the", "the n", "n terminus", "terminus of", "of rhophilins", "followed by", "by a", "a bro1", "bro1 domain", "characteristic of", "of proteins", "proteins involved", "involved in", "in protein", "kinase c", "c signaling", "and a", "a c", "c terminal", "terminal pdz", "pdz domain.", "domain. rhoa:gtp", "rhoa:gtp binds", "binds both", "both rhpn1", "rhpn1 and", "and rhpn2", "rhpn2 and", "and these", "these interactions", "interactions may", "may be", "be involved", "in organization", "organization of", "of the", "the actin", "actin cytoskeleton", "cytoskeleton and/or", "and/or cell", "cell motility", "watanabe et", "fujita et", "peck et", "al. 2002", "2002 .", ". rhob:gtp", "rhob:gtp recruits", "recruits rhpn2", "rhpn2 to", "to endosomes", "endosomes which", "which may", "function of", "of thyroid", "thyroid cells", "mircescu et", "rhotekin rtkn", "is a protein", "a protein with", "protein with an", "with an n", "an n terminally", "n terminally located", "terminally located rho", "located rho gtpase", "rho gtpase binding", "gtpase binding domain", "domain that", "that shares a", "shares a limited", "a limited sequence", "limited sequence homology", "sequence homology with", "homology with pkns", "with pkns and", "pkns and rhophilins.", "and rhophilins. rtkn", "rhophilins. rtkn binds", "rtkn binds to", "binds to gtp", "to gtp bound", "gtp bound rhoa", "rhoa rhob", "rhob and rhoc", "and rhoc and", "rhoc and can", "and can inhibit", "can inhibit their", "inhibit their gtpase", "their gtpase activity", "activity reid", "reid et al.", "et al. 1996", "1996 fu", "fu et al.", "et al. 2000", "which can be", "can be corroborated", "be corroborated by", "corroborated by protein", "by protein kinase", "protein kinase d", "kinase d mediated", "d mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of rtkn", "rtkn pusapati", "pusapati et al.", "et al. 2012", "al. 2012 .", "2012 . rtkn", ". rtkn is", "rtkn is implicated", "is implicated in", "implicated in the", "in the establishment", "the establishment of", "establishment of cell", "of cell polarity", "polarity sudo", "sudo et al.", "et al. 2006", "organization ito", "ito et al.", "et al. 2005", "2005 sudo", "et al. 2007", "2007 and", "and stimulation of", "stimulation of srf", "of srf mediated", "srf mediated transcription", "transcription reynaud", "reynaud et al.", "al. 2000 .", "2000 . rtkn", ". rtkn can", "rtkn can have", "can have an", "have an anti", "an anti apoptotic", "anti apoptotic effect", "apoptotic effect that", "effect that depends", "that depends on", "depends on the", "on the activation", "the activation of", "activation of nfkb", "nfkb nf", "liu et al.", "et al. 2004", "al. 2004 .", "2004 . rtkn2", "rtkn2 rhotekin", "2 is", "is another rhotekin", "another rhotekin exclusively", "rhotekin exclusively expressed", "exclusively expressed in", "expressed in lymphocytes", "lymphocytes collier", "collier et al.", "2004 . the", ". the function", "the function and", "function and the", "and the mechanism", "the mechanism of", "mechanism of action", "of action of", "action of rtkn2", "of rtkn2 are", "rtkn2 are unknown.

rhophillins", "are unknown.

rhophillins include", "unknown.

rhophillins include two", "include two family", "two family members", "1 rhnp1", "rhnp1 and", "and rhophilin 2", "2 rhpn2", "rhpn2 with", "with ~75% sequence", "~75% sequence identity.", "sequence identity. a", "identity. a rho", "a rho gtpase", "binding domain is", "domain is located", "is located at", "located at the", "at the n", "the n terminus", "n terminus of", "terminus of rhophilins", "rhophilins followed", "followed by a", "by a bro1", "a bro1 domain", "domain characteristic", "characteristic of proteins", "of proteins involved", "proteins involved in", "involved in protein", "in protein kinase", "protein kinase c", "kinase c signaling", "signaling and", "and a c", "a c terminal", "c terminal pdz", "terminal pdz domain.", "pdz domain. rhoa:gtp", "domain. rhoa:gtp binds", "rhoa:gtp binds both", "binds both rhpn1", "both rhpn1 and", "rhpn1 and rhpn2", "and rhpn2 and", "rhpn2 and these", "and these interactions", "these interactions may", "interactions may be", "may be involved", "be involved in", "involved in organization", "in organization of", "organization of the", "of the actin", "the actin cytoskeleton", "actin cytoskeleton and/or", "cytoskeleton and/or cell", "and/or cell motility", "motility watanabe", "watanabe et al.", "1996 fujita", "fujita et al.", "2000 peck", "peck et al.", "et al. 2002", "al. 2002 .", "2002 . rhob:gtp", ". rhob:gtp recruits", "rhob:gtp recruits rhpn2", "recruits rhpn2 to", "rhpn2 to endosomes", "to endosomes which", "endosomes which may", "which may be", "involved in the", "in the function", "the function of", "function of thyroid", "of thyroid cells", "cells mircescu", "mircescu et al.", "rtkn is a", "is a protein with", "a protein with an", "protein with an n", "with an n terminally", "an n terminally located", "n terminally located rho", "terminally located rho gtpase", "located rho gtpase binding", "rho gtpase binding domain", "binding domain that", "domain that shares", "that shares a limited", "shares a limited sequence", "a limited sequence homology", "limited sequence homology with", "sequence homology with pkns", "homology with pkns and", "with pkns and rhophilins.", "pkns and rhophilins. rtkn", "and rhophilins. rtkn binds", "rhophilins. rtkn binds to", "rtkn binds to gtp", "binds to gtp bound", "to gtp bound rhoa", "bound rhoa rhob", "rhoa rhob and", "rhob and rhoc and", "and rhoc and can", "rhoc and can inhibit", "and can inhibit their", "can inhibit their gtpase", "inhibit their gtpase activity", "gtpase activity reid", "activity reid et", "reid et al. 1996", "al. 1996 fu", "1996 fu et", "fu et al. 2000", "2000 which", "which can be corroborated", "can be corroborated by", "be corroborated by protein", "corroborated by protein kinase", "by protein kinase d", "protein kinase d mediated", "kinase d mediated phosphorylation", "d mediated phosphorylation of", "mediated phosphorylation of rtkn", "of rtkn pusapati", "rtkn pusapati et", "pusapati et al. 2012", "et al. 2012 .", "al. 2012 . rtkn", "2012 . rtkn is", ". rtkn is implicated", "rtkn is implicated in", "is implicated in the", "implicated in the establishment", "in the establishment of", "the establishment of cell", "establishment of cell polarity", "cell polarity sudo", "polarity sudo et", "sudo et al. 2006", "2006 septin", "septin organization ito", "organization ito et", "ito et al. 2005", "al. 2005 sudo", "2005 sudo et", "sudo et al. 2007", "al. 2007 and", "2007 and stimulation", "and stimulation of srf", "stimulation of srf mediated", "of srf mediated transcription", "mediated transcription reynaud", "transcription reynaud et", "reynaud et al. 2000", "et al. 2000 .", "al. 2000 . rtkn", "2000 . rtkn can", ". rtkn can have", "rtkn can have an", "can have an anti", "have an anti apoptotic", "an anti apoptotic effect", "anti apoptotic effect that", "apoptotic effect that depends", "effect that depends on", "that depends on the", "depends on the activation", "on the activation of", "the activation of nfkb", "of nfkb nf", "nfkb nf kappab", "kappab liu", "liu et al. 2004", "et al. 2004 .", "al. 2004 . rtkn2", ". rtkn2 rhotekin", "rtkn2 rhotekin 2", "rhotekin 2 is", "2 is another", "is another rhotekin exclusively", "another rhotekin exclusively expressed", "rhotekin exclusively expressed in", "exclusively expressed in lymphocytes", "in lymphocytes collier", "lymphocytes collier et", "collier et al. 2004", "al. 2004 . the", "2004 . the function", ". the function and", "the function and the", "function and the mechanism", "and the mechanism of", "the mechanism of action", "mechanism of action of", "of action of rtkn2", "action of rtkn2 are", "of rtkn2 are unknown.

rhophillins", "rtkn2 are unknown.

rhophillins include", "are unknown.

rhophillins include two", "unknown.

rhophillins include two family", "include two family members", "members rhophilin", "rhophilin 1 rhnp1", "rhnp1 and rhophilin", "rhophilin 2 rhpn2", "rhpn2 with ~75%", "with ~75% sequence identity.", "~75% sequence identity. a", "sequence identity. a rho", "identity. a rho gtpase", "a rho gtpase binding", "gtpase binding domain is", "binding domain is located", "domain is located at", "is located at the", "located at the n", "at the n terminus", "the n terminus of", "n terminus of rhophilins", "of rhophilins followed", "rhophilins followed by", "followed by a bro1", "by a bro1 domain", "bro1 domain characteristic", "domain characteristic of", "characteristic of proteins involved", "of proteins involved in", "proteins involved in protein", "involved in protein kinase", "in protein kinase c", "protein kinase c signaling", "c signaling and", "signaling and a", "and a c terminal", "a c terminal pdz", "c terminal pdz domain.", "terminal pdz domain. rhoa:gtp", "pdz domain. rhoa:gtp binds", "domain. rhoa:gtp binds both", "rhoa:gtp binds both rhpn1", "binds both rhpn1 and", "both rhpn1 and rhpn2", "rhpn1 and rhpn2 and", "and rhpn2 and these", "rhpn2 and these interactions", "and these interactions may", "these interactions may be", "interactions may be involved", "may be involved in", "be involved in organization", "involved in organization of", "in organization of the", "organization of the actin", "of the actin cytoskeleton", "the actin cytoskeleton and/or", "actin cytoskeleton and/or cell", "cytoskeleton and/or cell motility", "cell motility watanabe", "motility watanabe et", "watanabe et al. 1996", "al. 1996 fujita", "1996 fujita et", "fujita et al. 2000", "al. 2000 peck", "2000 peck et", "peck et al. 2002", "et al. 2002 .", "al. 2002 . rhob:gtp", "2002 . rhob:gtp recruits", ". rhob:gtp recruits rhpn2", "rhob:gtp recruits rhpn2 to", "recruits rhpn2 to endosomes", "rhpn2 to endosomes which", "to endosomes which may", "endosomes which may be", "which may be involved", "be involved in the", "involved in the function", "in the function of", "the function of thyroid", "function of thyroid cells", "thyroid cells mircescu", "cells mircescu et", "mircescu et al. 2002", "rhotekin rtkn is", "rtkn is a protein", "is a protein with an", "a protein with an n", "protein with an n terminally", "with an n terminally located", "an n terminally located rho", "n terminally located rho gtpase", "terminally located rho gtpase binding", "located rho gtpase binding domain", "gtpase binding domain that", "binding domain that shares", "domain that shares a", "that shares a limited sequence", "shares a limited sequence homology", "a limited sequence homology with", "limited sequence homology with pkns", "sequence homology with pkns and", "homology with pkns and rhophilins.", "with pkns and rhophilins. rtkn", "pkns and rhophilins. rtkn binds", "and rhophilins. rtkn binds to", "rhophilins. rtkn binds to gtp", "rtkn binds to gtp bound", "binds to gtp bound rhoa", "gtp bound rhoa rhob", "bound rhoa rhob and", "rhoa rhob and rhoc", "rhob and rhoc and can", "and rhoc and can inhibit", "rhoc and can inhibit their", "and can inhibit their gtpase", "can inhibit their gtpase activity", "their gtpase activity reid", "gtpase activity reid et", "activity reid et al.", "et al. 1996 fu", "al. 1996 fu et", "1996 fu et al.", "al. 2000 which", "2000 which can", "which can be corroborated by", "can be corroborated by protein", "be corroborated by protein kinase", "corroborated by protein kinase d", "by protein kinase d mediated", "protein kinase d mediated phosphorylation", "kinase d mediated phosphorylation of", "d mediated phosphorylation of rtkn", "phosphorylation of rtkn pusapati", "of rtkn pusapati et", "rtkn pusapati et al.", "pusapati et al. 2012 .", "et al. 2012 . rtkn", "al. 2012 . rtkn is", "2012 . rtkn is implicated", ". rtkn is implicated in", "rtkn is implicated in the", "is implicated in the establishment", "implicated in the establishment of", "in the establishment of cell", "the establishment of cell polarity", "of cell polarity sudo", "cell polarity sudo et", "polarity sudo et al.", "al. 2006 septin", "2006 septin organization", "septin organization ito et", "organization ito et al.", "et al. 2005 sudo", "al. 2005 sudo et", "2005 sudo et al.", "et al. 2007 and", "al. 2007 and stimulation", "2007 and stimulation of", "and stimulation of srf mediated", "stimulation of srf mediated transcription", "srf mediated transcription reynaud", "mediated transcription reynaud et", "transcription reynaud et al.", "reynaud et al. 2000 .", "et al. 2000 . rtkn", "al. 2000 . rtkn can", "2000 . rtkn can have", ". rtkn can have an", "rtkn can have an anti", "can have an anti apoptotic", "have an anti apoptotic effect", "an anti apoptotic effect that", "anti apoptotic effect that depends", "apoptotic effect that depends on", "effect that depends on the", "that depends on the activation", "depends on the activation of", "on the activation of nfkb", "activation of nfkb nf", "of nfkb nf kappab", "nf kappab liu", "kappab liu et", "liu et al. 2004 .", "et al. 2004 . rtkn2", "2004 . rtkn2 rhotekin", ". rtkn2 rhotekin 2", "rhotekin 2 is another", "2 is another rhotekin", "is another rhotekin exclusively expressed", "another rhotekin exclusively expressed in", "rhotekin exclusively expressed in lymphocytes", "expressed in lymphocytes collier", "in lymphocytes collier et", "lymphocytes collier et al.", "collier et al. 2004 .", "et al. 2004 . the", "al. 2004 . the function", "2004 . the function and", ". the function and the", "the function and the mechanism", "function and the mechanism of", "and the mechanism of action", "the mechanism of action of", "mechanism of action of rtkn2", "of action of rtkn2 are", "action of rtkn2 are unknown.

rhophillins", "of rtkn2 are unknown.

rhophillins include", "rtkn2 are unknown.

rhophillins include two", "are unknown.

rhophillins include two family", "unknown.

rhophillins include two family members", "family members rhophilin", "members rhophilin 1", "1 rhnp1 and", "rhnp1 and rhophilin 2", "and rhophilin 2 rhpn2", "2 rhpn2 with", "rhpn2 with ~75% sequence", "with ~75% sequence identity. a", "~75% sequence identity. a rho", "sequence identity. a rho gtpase", "identity. a rho gtpase binding", "a rho gtpase binding domain", "rho gtpase binding domain is", "gtpase binding domain is located", "binding domain is located at", "domain is located at the", "is located at the n", "located at the n terminus", "at the n terminus of", "the n terminus of rhophilins", "terminus of rhophilins followed", "of rhophilins followed by", "rhophilins followed by a", "followed by a bro1 domain", "a bro1 domain characteristic", "bro1 domain characteristic of", "domain characteristic of proteins", "characteristic of proteins involved in", "of proteins involved in protein", "proteins involved in protein kinase", "involved in protein kinase c", "in protein kinase c signaling", "kinase c signaling and", "c signaling and a", "signaling and a c", "and a c terminal pdz", "a c terminal pdz domain.", "c terminal pdz domain. rhoa:gtp", "terminal pdz domain. rhoa:gtp binds", "pdz domain. rhoa:gtp binds both", "domain. rhoa:gtp binds both rhpn1", "rhoa:gtp binds both rhpn1 and", "binds both rhpn1 and rhpn2", "both rhpn1 and rhpn2 and", "rhpn1 and rhpn2 and these", "and rhpn2 and these interactions", "rhpn2 and these interactions may", "and these interactions may be", "these interactions may be involved", "interactions may be involved in", "may be involved in organization", "be involved in organization of", "involved in organization of the", "in organization of the actin", "organization of the actin cytoskeleton", "of the actin cytoskeleton and/or", "the actin cytoskeleton and/or cell", "actin cytoskeleton and/or cell motility", "and/or cell motility watanabe", "cell motility watanabe et", "motility watanabe et al.", "et al. 1996 fujita", "al. 1996 fujita et", "1996 fujita et al.", "et al. 2000 peck", "al. 2000 peck et", "2000 peck et al.", "peck et al. 2002 .", "et al. 2002 . rhob:gtp", "al. 2002 . rhob:gtp recruits", "2002 . rhob:gtp recruits rhpn2", ". rhob:gtp recruits rhpn2 to", "rhob:gtp recruits rhpn2 to endosomes", "recruits rhpn2 to endosomes which", "rhpn2 to endosomes which may", "to endosomes which may be", "endosomes which may be involved", "which may be involved in", "may be involved in the", "be involved in the function", "involved in the function of", "in the function of thyroid", "the function of thyroid cells", "of thyroid cells mircescu", "thyroid cells mircescu et", "cells mircescu et al.", "mircescu et al. 2002 ." ] }, { "record_id": "GLY_000594_1_478", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5668541", "r hsa", "hsa 5668541", "r hsa 5668541" ] }, { "record_id": "GLY_000594_1_478", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tnfr2 non", "non canonical", "canonical nf", "nf kb", "kb pathway", "tnfr2 non canonical", "non canonical nf", "canonical nf kb", "nf kb pathway", "tnfr2 non canonical nf", "non canonical nf kb", "canonical nf kb pathway", "tnfr2 non canonical nf kb", "non canonical nf kb pathway", "tumor necrosis", "necrosis factor", "factor alpha", "exerts a", "a wide", "wide range", "range of", "of biological", "biological effects", "effects through", "through tnf", "tnf receptor", "receptor 1", "and tnf", "receptor 2", "tnfr2 .", ". under", "under normal", "normal physiological", "physiological conditions", "conditions tnfr2", "tnfr2 exhibits", "exhibits more", "more restricted", "restricted expression", "being found", "found on", "on certain", "certain subpopulation", "subpopulation of", "of immune", "immune cells", "cells and", "and few", "few other", "other cell", "cell types", "grell et", "et al.", "al. 1995", ". tnfr1", "tnfr1 mediated", "mediated signalling", "signalling pathways", "pathways have", "have been", "been very", "very well", "well characterized", "characterized but", "tnfr2 has", "has been", "been much", "much less", "less well", "well studied.", "studied. tnfr1", "tnfr1 upon", "upon activation", "activation by", "by tnfa", "tnfa activates", "activates apoptosis", "apoptosis through", "through two", "two pathways", "involving the", "the adaptor", "adaptor proteins", "proteins tnfr1", "tnfr1 associated", "associated death", "death domain", "and fas", "fas associated", "fadd .", ". in", "in contrast", "tnfr2 signalling", "signalling especially", "especially in", "in highly", "highly activated", "activated t", "t cells", "induces cell", "cell survival", "survival pathways", "pathways that", "that can", "can result", "result in", "in cell", "cell proliferation", "proliferation by", "by activating", "activating transcription", "transcription factor", "factor nf", "nuclear factor", "factor kb", "via the", "the alternative", "alternative non", "canonical route.", "route. tnfr2", "signalling seems", "seems to", "to play", "play an", "an important", "important role", "in particular", "particular for", "for the", "the function", "function of", "of regulatory", "regulatory t", "t cells.", "cells. it", "it offers", "offers protective", "protective roles", "roles in", "in several", "several disorders", "including autoimmune", "autoimmune diseases", "heart diseases", "demyelinating and", "and neurodegenerative", "neurodegenerative disorders", "disorders and", "and infectious", "infectious diseases", "faustman &", "& davis", "davis 2010", "2010 .
activation", ".
activation of", "of the", "the non", "canonical pathway", "pathway by", "by tnfr2", "tnfr2 is", "is mediated", "mediated through", "through a", "a signalling", "signalling complex", "complex that", "that includes", "includes tnf", "receptor associated", "associated factor", "traf2 and", "and traf3", "cellular inhibitor", "inhibitor of", "of apoptosis", "ciap1 and", "and ciap2", "and nf", "kb inducing", "inducing kinase", "nik .", "in this", "this complex", "complex traf3", "traf3 functions", "functions as", "as a", "a bridging", "bridging factor", "factor between", "between the", "the ciap1/2:traf2", "ciap1/2:traf2 complex", "complex and", "and nik.", "nik. in", "in resting", "resting cells", "cells ciap1/2", "ciap1/2 in", "in the", "the signalling", "complex mediates", "mediates k48", "k48 linked", "linked polyubiquitination", "polyubiquitination of", "of nik", "nik and", "and subsequent", "subsequent proteasomal", "proteasomal degradation", "degradation making", "making nik", "nik levels", "levels invisible.", "invisible. upon", "upon tnfr2", "tnfr2 stimulation", "traf2 is", "is recruited", "recruited to", "to the", "the intracellular", "intracellular traf", "traf binding", "binding motif", "motif and", "and this", "this also", "also indirectly", "indirectly recruits", "recruits traf1", "traf1 and", "and ciap1/2", "as well", "well as", "as traf3", "traf3 and", "and nik", "nik which", "which are", "are already", "already bound", "bound to", "to traf2", "traf2 in", "in unstimulated", "unstimulated cells.", "cells. traf2", "traf2 mediates", "mediates k63", "k63 linked", "linked ubiquitination", "ubiquitination of", "of ciap1/2", "ciap1/2 and", "this in", "in turn", "turn mediates", "mediates ciap", "ciap dependent", "dependent k48", "of traf3", "traf3 leading", "leading to", "the proteasome", "proteasome dependent", "dependent degradation", "degradation of", "the latter.", "latter. as", "traf3 is", "is degraded", "nik can", "can no", "no longer", "longer interact", "interact with", "with traf1/2:ciap", "traf1/2:ciap complex.", "complex. as", "a result", "result nik", "nik concentration", "concentration in", "the cytosol", "cytosol increases", "increases and", "nik gets", "gets stabilised", "stabilised and", "and activated.", "activated. activated", "activated nik", "nik phosphorylates", "phosphorylates ikkalpha", "which in", "turn phosphorylates", "phosphorylates p100", "subunit. phosphorylated", "phosphorylated p100", "p100 is", "is also", "also ubiquitinated", "ubiquitinated by", "by the", "the scf", "scf beta", "beta trcp", "trcp ubiquitin", "ubiquitin ligase", "ligase complex", "and is", "is subsequently", "subsequently processed", "processed by", "the proteaseome", "proteaseome to", "to p52", "which is", "is a", "a transcriptionally", "transcriptionally competent", "competent nf", "kb subunit", "subunit in", "in conjunction", "conjunction with", "with relb", "petrus et", "al. 2011", "sun 2011", "vallabhapurapu &", "& karin", "karin 2009", "2009 .", "tumor necrosis factor", "necrosis factor alpha", "alpha tnfa", "tnfa exerts", "exerts a wide", "a wide range", "wide range of", "range of biological", "of biological effects", "biological effects through", "effects through tnf", "through tnf receptor", "tnf receptor 1", "1 tnfr1", "tnfr1 and", "and tnf receptor", "tnf receptor 2", "2 tnfr2", "tnfr2 . under", ". under normal", "under normal physiological", "normal physiological conditions", "physiological conditions tnfr2", "conditions tnfr2 exhibits", "tnfr2 exhibits more", "exhibits more restricted", "more restricted expression", "expression being", "being found on", "found on certain", "on certain subpopulation", "certain subpopulation of", "subpopulation of immune", "of immune cells", "immune cells and", "cells and few", "and few other", "few other cell", "other cell types", "types grell", "grell et al.", "et al. 1995", "1995 .", ". tnfr1 mediated", "tnfr1 mediated signalling", "mediated signalling pathways", "signalling pathways have", "pathways have been", "have been very", "been very well", "very well characterized", "well characterized but", "but tnfr2", "tnfr2 has been", "has been much", "been much less", "much less well", "less well studied.", "well studied. tnfr1", "studied. tnfr1 upon", "tnfr1 upon activation", "upon activation by", "activation by tnfa", "by tnfa activates", "tnfa activates apoptosis", "activates apoptosis through", "apoptosis through two", "through two pathways", "pathways involving", "involving the adaptor", "the adaptor proteins", "adaptor proteins tnfr1", "proteins tnfr1 associated", "tnfr1 associated death", "associated death domain", "domain tradd", "tradd and", "and fas associated", "fas associated death", "domain fadd", "fadd . in", ". in contrast", "contrast tnfr2", "tnfr2 signalling especially", "signalling especially in", "especially in highly", "in highly activated", "highly activated t", "activated t cells", "cells induces", "induces cell survival", "cell survival pathways", "survival pathways that", "pathways that can", "that can result", "can result in", "result in cell", "in cell proliferation", "cell proliferation by", "proliferation by activating", "by activating transcription", "activating transcription factor", "transcription factor nf", "factor nf kb", "kb nuclear", "nuclear factor kb", "kb via", "via the alternative", "the alternative non", "alternative non canonical", "non canonical route.", "canonical route. tnfr2", "route. tnfr2 signalling", "tnfr2 signalling seems", "signalling seems to", "seems to play", "to play an", "play an important", "an important role", "role in", "in particular for", "particular for the", "for the function", "the function of", "function of regulatory", "of regulatory t", "regulatory t cells.", "t cells. it", "cells. it offers", "it offers protective", "offers protective roles", "protective roles in", "roles in several", "in several disorders", "disorders including", "including autoimmune diseases", "diseases heart", "diseases demyelinating", "demyelinating and neurodegenerative", "and neurodegenerative disorders", "neurodegenerative disorders and", "disorders and infectious", "and infectious diseases", "diseases faustman", "faustman & davis", "& davis 2010", "davis 2010 .
activation", "2010 .
activation of", ".
activation of the", "of the non", "the non canonical", "non canonical pathway", "canonical pathway by", "pathway by tnfr2", "by tnfr2 is", "tnfr2 is mediated", "is mediated through", "mediated through a", "through a signalling", "a signalling complex", "signalling complex that", "complex that includes", "that includes tnf", "includes tnf receptor", "tnf receptor associated", "receptor associated factor", "factor traf2", "traf2 and traf3", "cellular inhibitor of", "inhibitor of apoptosis", "apoptosis ciap1", "ciap1 and ciap2", "and nf kb", "nf kb inducing", "kb inducing kinase", "kinase nik", "nik . in", ". in this", "in this complex", "this complex traf3", "complex traf3 functions", "traf3 functions as", "functions as a", "as a bridging", "a bridging factor", "bridging factor between", "factor between the", "between the ciap1/2:traf2", "the ciap1/2:traf2 complex", "ciap1/2:traf2 complex and", "complex and nik.", "and nik. in", "nik. in resting", "in resting cells", "resting cells ciap1/2", "cells ciap1/2 in", "ciap1/2 in the", "in the signalling", "the signalling complex", "signalling complex mediates", "complex mediates k48", "mediates k48 linked", "k48 linked polyubiquitination", "linked polyubiquitination of", "polyubiquitination of nik", "of nik and", "nik and subsequent", "and subsequent proteasomal", "subsequent proteasomal degradation", "proteasomal degradation making", "degradation making nik", "making nik levels", "nik levels invisible.", "levels invisible. upon", "invisible. upon tnfr2", "upon tnfr2 stimulation", "stimulation traf2", "traf2 is recruited", "is recruited to", "recruited to the", "to the intracellular", "the intracellular traf", "intracellular traf binding", "traf binding motif", "binding motif and", "motif and this", "and this also", "this also indirectly", "also indirectly recruits", "indirectly recruits traf1", "recruits traf1 and", "traf1 and ciap1/2", "ciap1/2 as", "as well as", "well as traf3", "as traf3 and", "traf3 and nik", "and nik which", "nik which are", "which are already", "are already bound", "already bound to", "bound to traf2", "to traf2 in", "traf2 in unstimulated", "in unstimulated cells.", "unstimulated cells. traf2", "cells. traf2 mediates", "traf2 mediates k63", "mediates k63 linked", "k63 linked ubiquitination", "linked ubiquitination of", "ubiquitination of ciap1/2", "of ciap1/2 and", "ciap1/2 and this", "and this in", "this in turn", "in turn mediates", "turn mediates ciap", "mediates ciap dependent", "ciap dependent k48", "dependent k48 linked", "k48 linked ubiquitination", "ubiquitination of traf3", "of traf3 leading", "traf3 leading to", "leading to the", "to the proteasome", "the proteasome dependent", "proteasome dependent degradation", "dependent degradation of", "degradation of the", "of the latter.", "the latter. as", "latter. as traf3", "as traf3 is", "traf3 is degraded", "degraded nik", "nik can no", "can no longer", "no longer interact", "longer interact with", "interact with traf1/2:ciap", "with traf1/2:ciap complex.", "traf1/2:ciap complex. as", "complex. as a", "as a result", "a result nik", "result nik concentration", "nik concentration in", "concentration in the", "in the cytosol", "the cytosol increases", "cytosol increases and", "increases and nik", "and nik gets", "nik gets stabilised", "gets stabilised and", "stabilised and activated.", "and activated. activated", "activated. activated nik", "activated nik phosphorylates", "nik phosphorylates ikkalpha", "ikkalpha which", "which in turn", "in turn phosphorylates", "turn phosphorylates p100", "p100 nfkb2", "nfkb2 subunit.", "subunit. phosphorylated p100", "phosphorylated p100 is", "p100 is also", "is also ubiquitinated", "also ubiquitinated by", "ubiquitinated by the", "by the scf", "the scf beta", "scf beta trcp", "beta trcp ubiquitin", "trcp ubiquitin ligase", "ubiquitin ligase complex", "ligase complex and", "complex and is", "and is subsequently", "is subsequently processed", "subsequently processed by", "processed by the", "by the proteaseome", "the proteaseome to", "proteaseome to p52", "p52 which", "which is a", "is a transcriptionally", "a transcriptionally competent", "transcriptionally competent nf", "competent nf kb", "nf kb subunit", "kb subunit in", "subunit in conjunction", "in conjunction with", "conjunction with relb", "relb petrus", "petrus et al.", "et al. 2011", "2011 sun", "2011 vallabhapurapu", "vallabhapurapu & karin", "& karin 2009", "karin 2009 .", "tumor necrosis factor alpha", "factor alpha tnfa", "tnfa exerts a", "exerts a wide range", "a wide range of", "wide range of biological", "range of biological effects", "of biological effects through", "biological effects through tnf", "effects through tnf receptor", "through tnf receptor 1", "receptor 1 tnfr1", "tnfr1 and tnf", "and tnf receptor 2", "receptor 2 tnfr2", "2 tnfr2 .", "tnfr2 . under normal", ". under normal physiological", "under normal physiological conditions", "normal physiological conditions tnfr2", "physiological conditions tnfr2 exhibits", "conditions tnfr2 exhibits more", "tnfr2 exhibits more restricted", "exhibits more restricted expression", "restricted expression being", "expression being found", "being found on certain", "found on certain subpopulation", "on certain subpopulation of", "certain subpopulation of immune", "subpopulation of immune cells", "of immune cells and", "immune cells and few", "cells and few other", "and few other cell", "few other cell types", "cell types grell", "types grell et", "grell et al. 1995", "al. 1995 .", "1995 . tnfr1", ". tnfr1 mediated signalling", "tnfr1 mediated signalling pathways", "mediated signalling pathways have", "signalling pathways have been", "pathways have been very", "have been very well", "been very well characterized", "very well characterized but", "characterized but tnfr2", "but tnfr2 has", "tnfr2 has been much", "has been much less", "been much less well", "much less well studied.", "less well studied. tnfr1", "well studied. tnfr1 upon", "studied. tnfr1 upon activation", "tnfr1 upon activation by", "upon activation by tnfa", "activation by tnfa activates", "by tnfa activates apoptosis", "tnfa activates apoptosis through", "activates apoptosis through two", "apoptosis through two pathways", "two pathways involving", "pathways involving the", "involving the adaptor proteins", "the adaptor proteins tnfr1", "adaptor proteins tnfr1 associated", "proteins tnfr1 associated death", "tnfr1 associated death domain", "death domain tradd", "tradd and fas", "and fas associated death", "fas associated death domain", "death domain fadd", "domain fadd .", "fadd . in contrast", "in contrast tnfr2", "contrast tnfr2 signalling", "tnfr2 signalling especially in", "signalling especially in highly", "especially in highly activated", "in highly activated t", "highly activated t cells", "t cells induces", "cells induces cell", "induces cell survival pathways", "cell survival pathways that", "survival pathways that can", "pathways that can result", "that can result in", "can result in cell", "result in cell proliferation", "in cell proliferation by", "cell proliferation by activating", "proliferation by activating transcription", "by activating transcription factor", "activating transcription factor nf", "transcription factor nf kb", "nf kb nuclear", "kb nuclear factor", "factor kb via", "kb via the", "via the alternative non", "the alternative non canonical", "alternative non canonical route.", "non canonical route. tnfr2", "canonical route. tnfr2 signalling", "route. tnfr2 signalling seems", "tnfr2 signalling seems to", "signalling seems to play", "seems to play an", "to play an important", "play an important role", "important role in", "role in particular", "in particular for the", "particular for the function", "for the function of", "the function of regulatory", "function of regulatory t", "of regulatory t cells.", "regulatory t cells. it", "t cells. it offers", "cells. it offers protective", "it offers protective roles", "offers protective roles in", "protective roles in several", "roles in several disorders", "several disorders including", "disorders including autoimmune", "autoimmune diseases heart", "diseases heart diseases", "heart diseases demyelinating", "diseases demyelinating and", "demyelinating and neurodegenerative disorders", "and neurodegenerative disorders and", "neurodegenerative disorders and infectious", "disorders and infectious diseases", "infectious diseases faustman", "diseases faustman &", "faustman & davis 2010", "& davis 2010 .
activation", "davis 2010 .
activation of", "2010 .
activation of the", ".
activation of the non", "of the non canonical", "the non canonical pathway", "non canonical pathway by", "canonical pathway by tnfr2", "pathway by tnfr2 is", "by tnfr2 is mediated", "tnfr2 is mediated through", "is mediated through a", "mediated through a signalling", "through a signalling complex", "a signalling complex that", "signalling complex that includes", "complex that includes tnf", "that includes tnf receptor", "includes tnf receptor associated", "tnf receptor associated factor", "associated factor traf2", "factor traf2 and", "traf3 cellular", "cellular inhibitor of apoptosis", "of apoptosis ciap1", "apoptosis ciap1 and", "ciap2 and", "and nf kb inducing", "nf kb inducing kinase", "inducing kinase nik", "kinase nik .", "nik . in this", ". in this complex", "in this complex traf3", "this complex traf3 functions", "complex traf3 functions as", "traf3 functions as a", "functions as a bridging", "as a bridging factor", "a bridging factor between", "bridging factor between the", "factor between the ciap1/2:traf2", "between the ciap1/2:traf2 complex", "the ciap1/2:traf2 complex and", "ciap1/2:traf2 complex and nik.", "complex and nik. in", "and nik. in resting", "nik. in resting cells", "in resting cells ciap1/2", "resting cells ciap1/2 in", "cells ciap1/2 in the", "ciap1/2 in the signalling", "in the signalling complex", "the signalling complex mediates", "signalling complex mediates k48", "complex mediates k48 linked", "mediates k48 linked polyubiquitination", "k48 linked polyubiquitination of", "linked polyubiquitination of nik", "polyubiquitination of nik and", "of nik and subsequent", "nik and subsequent proteasomal", "and subsequent proteasomal degradation", "subsequent proteasomal degradation making", "proteasomal degradation making nik", "degradation making nik levels", "making nik levels invisible.", "nik levels invisible. upon", "levels invisible. upon tnfr2", "invisible. upon tnfr2 stimulation", "tnfr2 stimulation traf2", "stimulation traf2 is", "traf2 is recruited to", "is recruited to the", "recruited to the intracellular", "to the intracellular traf", "the intracellular traf binding", "intracellular traf binding motif", "traf binding motif and", "binding motif and this", "motif and this also", "and this also indirectly", "this also indirectly recruits", "also indirectly recruits traf1", "indirectly recruits traf1 and", "recruits traf1 and ciap1/2", "and ciap1/2 as", "ciap1/2 as well", "as well as traf3", "well as traf3 and", "as traf3 and nik", "traf3 and nik which", "and nik which are", "nik which are already", "which are already bound", "are already bound to", "already bound to traf2", "bound to traf2 in", "to traf2 in unstimulated", "traf2 in unstimulated cells.", "in unstimulated cells. traf2", "unstimulated cells. traf2 mediates", "cells. traf2 mediates k63", "traf2 mediates k63 linked", "mediates k63 linked ubiquitination", "k63 linked ubiquitination of", "linked ubiquitination of ciap1/2", "ubiquitination of ciap1/2 and", "of ciap1/2 and this", "ciap1/2 and this in", "and this in turn", "this in turn mediates", "in turn mediates ciap", "turn mediates ciap dependent", "mediates ciap dependent k48", "ciap dependent k48 linked", "dependent k48 linked ubiquitination", "k48 linked ubiquitination of", "linked ubiquitination of traf3", "ubiquitination of traf3 leading", "of traf3 leading to", "traf3 leading to the", "leading to the proteasome", "to the proteasome dependent", "the proteasome dependent degradation", "proteasome dependent degradation of", "dependent degradation of the", "degradation of the latter.", "of the latter. as", "the latter. as traf3", "latter. as traf3 is", "as traf3 is degraded", "is degraded nik", "degraded nik can", "nik can no longer", "can no longer interact", "no longer interact with", "longer interact with traf1/2:ciap", "interact with traf1/2:ciap complex.", "with traf1/2:ciap complex. as", "traf1/2:ciap complex. as a", "complex. as a result", "as a result nik", "a result nik concentration", "result nik concentration in", "nik concentration in the", "concentration in the cytosol", "in the cytosol increases", "the cytosol increases and", "cytosol increases and nik", "increases and nik gets", "and nik gets stabilised", "nik gets stabilised and", "gets stabilised and activated.", "stabilised and activated. activated", "and activated. activated nik", "activated. activated nik phosphorylates", "activated nik phosphorylates ikkalpha", "phosphorylates ikkalpha which", "ikkalpha which in", "which in turn phosphorylates", "in turn phosphorylates p100", "phosphorylates p100 nfkb2", "nfkb2 subunit. phosphorylated", "subunit. phosphorylated p100 is", "phosphorylated p100 is also", "p100 is also ubiquitinated", "is also ubiquitinated by", "also ubiquitinated by the", "ubiquitinated by the scf", "by the scf beta", "the scf beta trcp", "scf beta trcp ubiquitin", "beta trcp ubiquitin ligase", "trcp ubiquitin ligase complex", "ubiquitin ligase complex and", "ligase complex and is", "complex and is subsequently", "and is subsequently processed", "is subsequently processed by", "subsequently processed by the", "processed by the proteaseome", "by the proteaseome to", "the proteaseome to p52", "to p52 which", "p52 which is", "which is a transcriptionally", "is a transcriptionally competent", "a transcriptionally competent nf", "transcriptionally competent nf kb", "competent nf kb subunit", "nf kb subunit in", "kb subunit in conjunction", "subunit in conjunction with", "in conjunction with relb", "with relb petrus", "relb petrus et", "petrus et al. 2011", "al. 2011 sun", "2011 sun 2011", "sun 2011 vallabhapurapu", "2011 vallabhapurapu &", "vallabhapurapu & karin 2009", "& karin 2009 .", "necrosis factor alpha tnfa", "alpha tnfa exerts", "tnfa exerts a wide", "exerts a wide range of", "a wide range of biological", "wide range of biological effects", "range of biological effects through", "of biological effects through tnf", "biological effects through tnf receptor", "effects through tnf receptor 1", "tnf receptor 1 tnfr1", "1 tnfr1 and", "tnfr1 and tnf receptor", "tnf receptor 2 tnfr2", "receptor 2 tnfr2 .", "2 tnfr2 . under", "tnfr2 . under normal physiological", ". under normal physiological conditions", "under normal physiological conditions tnfr2", "normal physiological conditions tnfr2 exhibits", "physiological conditions tnfr2 exhibits more", "conditions tnfr2 exhibits more restricted", "tnfr2 exhibits more restricted expression", "more restricted expression being", "restricted expression being found", "expression being found on", "being found on certain subpopulation", "found on certain subpopulation of", "on certain subpopulation of immune", "certain subpopulation of immune cells", "subpopulation of immune cells and", "of immune cells and few", "immune cells and few other", "cells and few other cell", "and few other cell types", "other cell types grell", "cell types grell et", "types grell et al.", "et al. 1995 .", "al. 1995 . tnfr1", "1995 . tnfr1 mediated", ". tnfr1 mediated signalling pathways", "tnfr1 mediated signalling pathways have", "mediated signalling pathways have been", "signalling pathways have been very", "pathways have been very well", "have been very well characterized", "been very well characterized but", "well characterized but tnfr2", "characterized but tnfr2 has", "but tnfr2 has been", "tnfr2 has been much less", "has been much less well", "been much less well studied.", "much less well studied. tnfr1", "less well studied. tnfr1 upon", "well studied. tnfr1 upon activation", "studied. tnfr1 upon activation by", "tnfr1 upon activation by tnfa", "upon activation by tnfa activates", "activation by tnfa activates apoptosis", "by tnfa activates apoptosis through", "tnfa activates apoptosis through two", "activates apoptosis through two pathways", "through two pathways involving", "two pathways involving the", "pathways involving the adaptor", "involving the adaptor proteins tnfr1", "the adaptor proteins tnfr1 associated", "adaptor proteins tnfr1 associated death", "proteins tnfr1 associated death domain", "associated death domain tradd", "domain tradd and", "tradd and fas associated", "and fas associated death domain", "associated death domain fadd", "death domain fadd .", "domain fadd . in", ". in contrast tnfr2", "in contrast tnfr2 signalling", "contrast tnfr2 signalling especially", "tnfr2 signalling especially in highly", "signalling especially in highly activated", "especially in highly activated t", "in highly activated t cells", "activated t cells induces", "t cells induces cell", "cells induces cell survival", "induces cell survival pathways that", "cell survival pathways that can", "survival pathways that can result", "pathways that can result in", "that can result in cell", "can result in cell proliferation", "result in cell proliferation by", "in cell proliferation by activating", "cell proliferation by activating transcription", "proliferation by activating transcription factor", "by activating transcription factor nf", "activating transcription factor nf kb", "factor nf kb nuclear", "nf kb nuclear factor", "kb nuclear factor kb", "nuclear factor kb via", "factor kb via the", "kb via the alternative", "via the alternative non canonical", "the alternative non canonical route.", "alternative non canonical route. tnfr2", "non canonical route. tnfr2 signalling", "canonical route. tnfr2 signalling seems", "route. tnfr2 signalling seems to", "tnfr2 signalling seems to play", "signalling seems to play an", "seems to play an important", "to play an important role", "an important role in", "important role in particular", "role in particular for", "in particular for the function", "particular for the function of", "for the function of regulatory", "the function of regulatory t", "function of regulatory t cells.", "of regulatory t cells. it", "regulatory t cells. it offers", "t cells. it offers protective", "cells. it offers protective roles", "it offers protective roles in", "offers protective roles in several", "protective roles in several disorders", "in several disorders including", "several disorders including autoimmune", "disorders including autoimmune diseases", "including autoimmune diseases heart", "autoimmune diseases heart diseases", "heart diseases demyelinating and", "diseases demyelinating and neurodegenerative", "demyelinating and neurodegenerative disorders and", "and neurodegenerative disorders and infectious", "neurodegenerative disorders and infectious diseases", "and infectious diseases faustman", "infectious diseases faustman &", "diseases faustman & davis", "faustman & davis 2010 .
activation", "& davis 2010 .
activation of", "davis 2010 .
activation of the", "2010 .
activation of the non", ".
activation of the non canonical", "of the non canonical pathway", "the non canonical pathway by", "non canonical pathway by tnfr2", "canonical pathway by tnfr2 is", "pathway by tnfr2 is mediated", "by tnfr2 is mediated through", "tnfr2 is mediated through a", "is mediated through a signalling", "mediated through a signalling complex", "through a signalling complex that", "a signalling complex that includes", "signalling complex that includes tnf", "complex that includes tnf receptor", "that includes tnf receptor associated", "includes tnf receptor associated factor", "receptor associated factor traf2", "associated factor traf2 and", "factor traf2 and traf3", "and traf3 cellular", "traf3 cellular inhibitor", "inhibitor of apoptosis ciap1", "of apoptosis ciap1 and", "apoptosis ciap1 and ciap2", "and ciap2 and", "ciap2 and nf", "and nf kb inducing kinase", "kb inducing kinase nik", "inducing kinase nik .", "kinase nik . in", "nik . in this complex", ". in this complex traf3", "in this complex traf3 functions", "this complex traf3 functions as", "complex traf3 functions as a", "traf3 functions as a bridging", "functions as a bridging factor", "as a bridging factor between", "a bridging factor between the", "bridging factor between the ciap1/2:traf2", "factor between the ciap1/2:traf2 complex", "between the ciap1/2:traf2 complex and", "the ciap1/2:traf2 complex and nik.", "ciap1/2:traf2 complex and nik. in", "complex and nik. in resting", "and nik. in resting cells", "nik. in resting cells ciap1/2", "in resting cells ciap1/2 in", "resting cells ciap1/2 in the", "cells ciap1/2 in the signalling", "ciap1/2 in the signalling complex", "in the signalling complex mediates", "the signalling complex mediates k48", "signalling complex mediates k48 linked", "complex mediates k48 linked polyubiquitination", "mediates k48 linked polyubiquitination of", "k48 linked polyubiquitination of nik", "linked polyubiquitination of nik and", "polyubiquitination of nik and subsequent", "of nik and subsequent proteasomal", "nik and subsequent proteasomal degradation", "and subsequent proteasomal degradation making", "subsequent proteasomal degradation making nik", "proteasomal degradation making nik levels", "degradation making nik levels invisible.", "making nik levels invisible. upon", "nik levels invisible. upon tnfr2", "levels invisible. upon tnfr2 stimulation", "upon tnfr2 stimulation traf2", "tnfr2 stimulation traf2 is", "stimulation traf2 is recruited", "traf2 is recruited to the", "is recruited to the intracellular", "recruited to the intracellular traf", "to the intracellular traf binding", "the intracellular traf binding motif", "intracellular traf binding motif and", "traf binding motif and this", "binding motif and this also", "motif and this also indirectly", "and this also indirectly recruits", "this also indirectly recruits traf1", "also indirectly recruits traf1 and", "indirectly recruits traf1 and ciap1/2", "traf1 and ciap1/2 as", "and ciap1/2 as well", "ciap1/2 as well as", "as well as traf3 and", "well as traf3 and nik", "as traf3 and nik which", "traf3 and nik which are", "and nik which are already", "nik which are already bound", "which are already bound to", "are already bound to traf2", "already bound to traf2 in", "bound to traf2 in unstimulated", "to traf2 in unstimulated cells.", "traf2 in unstimulated cells. traf2", "in unstimulated cells. traf2 mediates", "unstimulated cells. traf2 mediates k63", "cells. traf2 mediates k63 linked", "traf2 mediates k63 linked ubiquitination", "mediates k63 linked ubiquitination of", "k63 linked ubiquitination of ciap1/2", "linked ubiquitination of ciap1/2 and", "ubiquitination of ciap1/2 and this", "of ciap1/2 and this in", "ciap1/2 and this in turn", "and this in turn mediates", "this in turn mediates ciap", "in turn mediates ciap dependent", "turn mediates ciap dependent k48", "mediates ciap dependent k48 linked", "ciap dependent k48 linked ubiquitination", "dependent k48 linked ubiquitination of", "k48 linked ubiquitination of traf3", "linked ubiquitination of traf3 leading", "ubiquitination of traf3 leading to", "of traf3 leading to the", "traf3 leading to the proteasome", "leading to the proteasome dependent", "to the proteasome dependent degradation", "the proteasome dependent degradation of", "proteasome dependent degradation of the", "dependent degradation of the latter.", "degradation of the latter. as", "of the latter. as traf3", "the latter. as traf3 is", "latter. as traf3 is degraded", "traf3 is degraded nik", "is degraded nik can", "degraded nik can no", "nik can no longer interact", "can no longer interact with", "no longer interact with traf1/2:ciap", "longer interact with traf1/2:ciap complex.", "interact with traf1/2:ciap complex. as", "with traf1/2:ciap complex. as a", "traf1/2:ciap complex. as a result", "complex. as a result nik", "as a result nik concentration", "a result nik concentration in", "result nik concentration in the", "nik concentration in the cytosol", "concentration in the cytosol increases", "in the cytosol increases and", "the cytosol increases and nik", "cytosol increases and nik gets", "increases and nik gets stabilised", "and nik gets stabilised and", "nik gets stabilised and activated.", "gets stabilised and activated. activated", "stabilised and activated. activated nik", "and activated. activated nik phosphorylates", "activated. activated nik phosphorylates ikkalpha", "nik phosphorylates ikkalpha which", "phosphorylates ikkalpha which in", "ikkalpha which in turn", "which in turn phosphorylates p100", "turn phosphorylates p100 nfkb2", "p100 nfkb2 subunit.", "nfkb2 subunit. phosphorylated p100", "subunit. phosphorylated p100 is also", "phosphorylated p100 is also ubiquitinated", "p100 is also ubiquitinated by", "is also ubiquitinated by the", "also ubiquitinated by the scf", "ubiquitinated by the scf beta", "by the scf beta trcp", "the scf beta trcp ubiquitin", "scf beta trcp ubiquitin ligase", "beta trcp ubiquitin ligase complex", "trcp ubiquitin ligase complex and", "ubiquitin ligase complex and is", "ligase complex and is subsequently", "complex and is subsequently processed", "and is subsequently processed by", "is subsequently processed by the", "subsequently processed by the proteaseome", "processed by the proteaseome to", "by the proteaseome to p52", "proteaseome to p52 which", "to p52 which is", "p52 which is a", "which is a transcriptionally competent", "is a transcriptionally competent nf", "a transcriptionally competent nf kb", "transcriptionally competent nf kb subunit", "competent nf kb subunit in", "nf kb subunit in conjunction", "kb subunit in conjunction with", "subunit in conjunction with relb", "conjunction with relb petrus", "with relb petrus et", "relb petrus et al.", "et al. 2011 sun", "al. 2011 sun 2011", "sun 2011 vallabhapurapu &", "2011 vallabhapurapu & karin", "vallabhapurapu & karin 2009 ." ] }, { "record_id": "GLY_000594_1_479", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5669034", "r hsa", "hsa 5669034", "r hsa 5669034" ] }, { "record_id": "GLY_000594_1_479", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tnfs bind", "bind their", "their physiological", "physiological receptors", "tnfs bind their", "bind their physiological", "their physiological receptors", "tnfs bind their physiological", "bind their physiological receptors", "tnfs bind their physiological receptors", "members of", "of the", "the tumour", "tumour necrosis", "necrosis factor", "factor superfamily", "and tnf", "tnf receptor", "receptor superfamily", "have crucial", "crucial roles", "roles in", "in both", "both innate", "innate and", "and adaptive", "adaptive immunity.", "immunity. these", "these members", "members are", "are implicated", "implicated in", "in various", "various acquired", "acquired or", "or genetic", "genetic human", "human diseases", "ranging from", "from septic", "septic shock", "shock to", "to autoimmune", "autoimmune disorders", "allograft rejection", "rejection and", "and cancer", "so et", "et al.", "al. 2006", "2006 .", "members of the", "of the tumour", "the tumour necrosis", "tumour necrosis factor", "necrosis factor superfamily", "superfamily tnfsf", "tnfsf and", "and tnf receptor", "tnf receptor superfamily", "superfamily tnfrsf", "tnfrsf have", "have crucial roles", "crucial roles in", "roles in both", "in both innate", "both innate and", "innate and adaptive", "and adaptive immunity.", "adaptive immunity. these", "immunity. these members", "these members are", "members are implicated", "are implicated in", "implicated in various", "in various acquired", "various acquired or", "acquired or genetic", "or genetic human", "genetic human diseases", "diseases ranging", "ranging from septic", "from septic shock", "septic shock to", "shock to autoimmune", "to autoimmune disorders", "disorders allograft", "allograft rejection and", "rejection and cancer", "cancer so", "so et al.", "et al. 2006", "al. 2006 .", "members of the tumour", "of the tumour necrosis", "the tumour necrosis factor", "tumour necrosis factor superfamily", "factor superfamily tnfsf", "tnfsf and tnf", "and tnf receptor superfamily", "receptor superfamily tnfrsf", "tnfrsf have crucial", "have crucial roles in", "crucial roles in both", "roles in both innate", "in both innate and", "both innate and adaptive", "innate and adaptive immunity.", "and adaptive immunity. these", "adaptive immunity. these members", "immunity. these members are", "these members are implicated", "members are implicated in", "are implicated in various", "implicated in various acquired", "in various acquired or", "various acquired or genetic", "acquired or genetic human", "or genetic human diseases", "human diseases ranging", "diseases ranging from", "ranging from septic shock", "from septic shock to", "septic shock to autoimmune", "shock to autoimmune disorders", "autoimmune disorders allograft", "disorders allograft rejection", "allograft rejection and cancer", "and cancer so", "cancer so et", "so et al. 2006", "et al. 2006 .", "members of the tumour necrosis", "of the tumour necrosis factor", "the tumour necrosis factor superfamily", "necrosis factor superfamily tnfsf", "superfamily tnfsf and", "tnfsf and tnf receptor", "tnf receptor superfamily tnfrsf", "superfamily tnfrsf have", "tnfrsf have crucial roles", "have crucial roles in both", "crucial roles in both innate", "roles in both innate and", "in both innate and adaptive", "both innate and adaptive immunity.", "innate and adaptive immunity. these", "and adaptive immunity. these members", "adaptive immunity. these members are", "immunity. these members are implicated", "these members are implicated in", "members are implicated in various", "are implicated in various acquired", "implicated in various acquired or", "in various acquired or genetic", "various acquired or genetic human", "acquired or genetic human diseases", "genetic human diseases ranging", "human diseases ranging from", "diseases ranging from septic", "ranging from septic shock to", "from septic shock to autoimmune", "septic shock to autoimmune disorders", "to autoimmune disorders allograft", "autoimmune disorders allograft rejection", "disorders allograft rejection and", "rejection and cancer so", "and cancer so et", "cancer so et al.", "so et al. 2006 ." ] }, { "record_id": "GLY_000594_1_480", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5673001", "r hsa", "hsa 5673001", "r hsa 5673001" ] }, { "record_id": "GLY_000594_1_480", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "raf/map kinase", "kinase cascade", "raf/map kinase cascade", "the ras", "ras raf", "raf mek", "mek erk", "erk pathway", "pathway regulates", "regulates processes", "processes such", "such as", "as proliferation", "senescence and", "and cell", "cell motility", "motility in", "in response", "response to", "to growth", "growth factors", "hormones and", "and cytokines", "among others.", "others. binding", "binding of", "of these", "these stimuli", "stimuli to", "to receptors", "receptors in", "in the", "the plasma", "plasma membrane", "membrane promotes", "promotes the", "the gef", "gef mediated", "mediated activation", "activation of", "of ras", "ras at", "at the", "membrane and", "and initiates", "initiates the", "the three", "three tiered", "tiered kinase", "cascade of", "of the", "the conventional", "conventional mapk", "mapk cascades.", "gtp bound", "bound ras", "ras recruits", "recruits raf", "the mapk", "mapk kinase", "kinase kinase", "and promotes", "promotes its", "its dimerization", "dimerization and", "and activation", "reviewed in", "in cseh", "cseh et", "et al", "mckay and", "and morrison", "wellbrock et", "2004 .", "activated raf", "raf phosphorylates", "phosphorylates the", "kinase proteins", "proteins mek1", "mek1 and", "and mek2", "also known", "known as", "as map2k1", "map2k1 and", "and map2k2", "which in", "in turn", "turn phophorylate", "phophorylate the", "the proline", "proline directed", "directed kinases", "kinases erk1", "erk1 and", "and 2", "as mapk3", "mapk3 and", "and mapk1", "in roskoski", "kryiakis and", "and avruch", "2012 .", "activated erk", "erk proteins", "proteins may", "may undergo", "undergo dimerization", "and have", "have identified", "identified targets", "targets in", "in both", "both the", "the nucleus", "nucleus and", "and the", "the cytosol", "consistent with", "with this", "a proportion", "proportion of", "of activated", "erk protein", "protein relocalizes", "relocalizes to", "to the", "nucleus in", "to stimuli", "roskoski 2012b", "turjanski et", "plotnikov et", "cargnello et", "2011 .", "although initially", "initially seen", "seen as", "as a", "a linear", "linear cascade", "cascade originating", "originating at", "and culminating", "culminating in", "the ras/raf", "ras/raf mapk", "mapk cascade", "cascade is", "is now", "now also", "known to", "to be", "be activated", "activated from", "from various", "various intracellular", "intracellular location.", "temporal and", "and spatial", "spatial specificity", "specificity of", "the cascade", "is achieved", "achieved in", "in part", "part through", "through the", "the interaction", "interaction of", "of pathway", "pathway components", "components with", "with numerous", "numerous scaffolding", "scaffolding proteins", "in mckay", "brown and", "and sacks", "2009 .", ".
", "
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", ".
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activated", ". activated raf", "activated raf phosphorylates the", "raf phosphorylates the mapk", "phosphorylates the mapk kinase", "the mapk kinase proteins", "mapk kinase proteins mek1", "kinase proteins mek1 and", "proteins mek1 and mek2", "and mek2 also", "mek2 also known", "also known as map2k1", "known as map2k1 and", "as map2k1 and map2k2", "map2k2 which", "which in turn phophorylate", "in turn phophorylate the", "turn phophorylate the proline", "phophorylate the proline directed", "the proline directed kinases", "proline directed kinases erk1", "directed kinases erk1 and", "kinases erk1 and 2", "and 2 also", "2 also known", "also known as mapk3", "known as mapk3 and", "as mapk3 and mapk1", "mapk1 reviewed", "in roskoski 2012a", "b kryiakis and", "and avruch 2012", "avruch 2012 .", "2012 . activated", ". activated erk", "activated erk proteins may", "erk proteins may undergo", "proteins may undergo dimerization", "may undergo dimerization and", "undergo dimerization and have", "dimerization and have identified", "and have identified targets", "have identified targets in", "identified targets in both", "targets in both the", "in both the nucleus", "both the nucleus and", "the nucleus and the", "nucleus and the cytosol", "the cytosol consistent", "cytosol consistent with", "with this a", "this a proportion", "a proportion of activated", "proportion of activated erk", "of activated erk protein", "activated erk protein relocalizes", "erk protein relocalizes to", "protein relocalizes to the", "relocalizes to the nucleus", "to the nucleus in", "the nucleus in response", "nucleus in response to", "in response to stimuli", "to stimuli reviewed", "stimuli reviewed in", "reviewed in roskoski 2012b", "roskoski 2012b turjanski", "2012b turjanski et", "et al 2007", "2007 plotnikov et", "et al 2010", "2010 cargnello et", "et al 2011", "al 2011 .", "2011 . although", ". although initially", "although initially seen as", "initially seen as a", "seen as a linear", "as a linear cascade", "a linear cascade originating", "linear cascade originating at", "cascade originating at the", "originating at the plasma", "plasma membrane and culminating", "membrane and culminating in", "and culminating in the", "culminating in the nucleus", "the nucleus the", "nucleus the ras/raf", "the ras/raf mapk cascade", "ras/raf mapk cascade is", "mapk cascade is now", "cascade is now also", "is now also known", "now also known to", "also known to be", "known to be activated", "to be activated from", "be activated from various", "activated from various intracellular", "from various intracellular location.", "intracellular location. temporal", "location. temporal and", "temporal and spatial specificity", "and spatial specificity of", "spatial specificity of the", "specificity of the cascade", "of the cascade is", "the cascade is achieved", "cascade is achieved in", "is achieved in part", "achieved in part through", "in part through the", "part through the interaction", "through the interaction of", "the interaction of pathway", "interaction of pathway components", "of pathway components with", "pathway components with numerous", "components with numerous scaffolding", "with numerous scaffolding proteins", "scaffolding proteins reviewed", "proteins reviewed in", "reviewed in mckay and", "in mckay and morrison", "2007 brown and", "and sacks 2009", "sacks 2009 .", "2009 .
the", ".
the importance", "
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while ~8%", "while ~8% of tumors", "~8% of tumors express", "of tumors express an", "tumors express an activated", "express an activated form", "an activated form of", "activated form of braf", "of braf roberts", "braf roberts and", "and der 2007", "2007 davies et", "et al 2002", "2002 cantwell dorris", "cantwell dorris et al", "the ras raf mek erk", "ras raf mek erk pathway", "raf mek erk pathway regulates", "mek erk pathway regulates processes", "erk pathway regulates processes such", "pathway regulates processes such as", "regulates processes such as proliferation", "such as proliferation differentiation", "proliferation differentiation survival", "differentiation survival senescence", "survival senescence and cell", "senescence and cell motility in", "and cell motility in response", "cell motility in response to", "motility in response to growth", "in response to growth factors", "to growth factors hormones", "growth factors hormones and", "factors hormones and cytokines", "hormones and cytokines among", "and cytokines among others.", "cytokines among others. binding", "among others. binding of these", "others. binding of these stimuli", "binding of these stimuli to", "of these stimuli to receptors", "these stimuli to receptors in", "stimuli to receptors in the", "to receptors in the plasma", "receptors in the plasma membrane", "in the plasma membrane promotes", "the plasma membrane promotes the", "plasma membrane promotes the gef", "membrane promotes the gef mediated", "promotes the gef mediated activation", "the gef mediated activation of", "gef mediated activation of ras", "mediated activation of ras at", "activation of ras at the", "of ras at the plasma", "ras at the plasma membrane", "at the plasma membrane and", "the plasma membrane and initiates", "plasma membrane and initiates the", "membrane and initiates the three", "and initiates the three tiered", "initiates the three tiered kinase", "the three tiered kinase cascade", "three tiered kinase cascade of", "tiered kinase cascade of the", "kinase cascade of the conventional", "cascade of the conventional mapk", "of the conventional mapk cascades.", "conventional mapk cascades. gtp", "mapk cascades. gtp bound", "cascades. gtp bound ras", "gtp bound ras recruits raf", "ras recruits raf the", "recruits raf the mapk", "raf the mapk kinase", "kinase kinase and", "kinase and promotes", "and promotes its dimerization and", "promotes its dimerization and activation", "dimerization and activation reviewed", "and activation reviewed in", "activation reviewed in cseh", "reviewed in cseh et al", "cseh et al 2014", "al 2014 roskoski", "2014 roskoski 2010", "roskoski 2010 mckay", "2010 mckay and morrison", "mckay and morrison 2007", "morrison 2007 wellbrock", "2007 wellbrock et al", "wellbrock et al 2004", "et al 2004 .", "2004 . activated raf", ". activated raf phosphorylates", "activated raf phosphorylates the mapk", "raf phosphorylates the mapk kinase", "phosphorylates the mapk kinase proteins", "the mapk kinase proteins mek1", "mapk kinase proteins mek1 and", "kinase proteins mek1 and mek2", "mek1 and mek2 also", "and mek2 also known", "mek2 also known as", "also known as map2k1 and", "known as map2k1 and map2k2", "and map2k2 which", "map2k2 which in", "which in turn phophorylate the", "in turn phophorylate the proline", "turn phophorylate the proline directed", "phophorylate the proline directed kinases", "the proline directed kinases erk1", "proline directed kinases erk1 and", "directed kinases erk1 and 2", "erk1 and 2 also", "and 2 also known", "2 also known as", "also known as mapk3 and", "known as mapk3 and mapk1", "and mapk1 reviewed", "mapk1 reviewed in", "reviewed in roskoski 2012a", "roskoski 2012a b", "2012a b kryiakis", "b kryiakis and avruch", "kryiakis and avruch 2012", "and avruch 2012 .", "2012 . activated erk", ". activated erk proteins", "activated erk proteins may undergo", "erk proteins may undergo dimerization", "proteins may undergo dimerization and", "may undergo dimerization and have", "undergo dimerization and have identified", "dimerization and have identified targets", "and have identified targets in", "have identified targets in both", "identified targets in both the", "targets in both the nucleus", "in both the nucleus and", "both the nucleus and the", "the nucleus and the cytosol", "and the cytosol consistent", "the cytosol consistent with", "cytosol consistent with this", "consistent with this a", "with this a proportion", "this a proportion of", "a proportion of activated erk", "proportion of activated erk protein", "of activated erk protein relocalizes", "activated erk protein relocalizes to", "erk protein relocalizes to the", "protein relocalizes to the nucleus", "relocalizes to the nucleus in", "to the nucleus in response", "the nucleus in response to", "nucleus in response to stimuli", "response to stimuli reviewed", "to stimuli reviewed in", "stimuli reviewed in roskoski", "in roskoski 2012b turjanski", "roskoski 2012b turjanski et", "2012b turjanski et al", "turjanski et al 2007", "al 2007 plotnikov", "2007 plotnikov et al", "plotnikov et al 2010", "al 2010 cargnello", "2010 cargnello et al", "cargnello et al 2011", "et al 2011 .", "2011 . although initially", ". although initially seen", "although initially seen as a", "initially seen as a linear", "seen as a linear cascade", "as a linear cascade originating", "a linear cascade originating at", "linear cascade originating at the", "cascade originating at the plasma", "originating at the plasma membrane", "the plasma membrane and culminating", "plasma membrane and culminating in", "membrane and culminating in the", "and culminating in the nucleus", "in the nucleus the", "the nucleus the ras/raf", "nucleus the ras/raf mapk", "the ras/raf mapk cascade is", "ras/raf mapk cascade is now", "mapk cascade is now also", "cascade is now also known", "is now also known to", "now also known to be", "also known to be activated", 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is always present", "that is always present at", "is always present at the", "always present at the plasma", "present at the plasma membrane", "the plasma membrane due", "plasma membrane due to", "membrane due to low", "due to low affinity for", "to low affinity for pip2.", "low affinity for pip2. therefore", "for pip2. therefore e17k", "pip2. therefore e17k substitution", "therefore e17k substitution abrogates", "e17k substitution abrogates the need", "substitution abrogates the need for", "abrogates the need for pi3k", "the need for pi3k in", "need for pi3k in akt1", "for pi3k in akt1 activation", "in akt1 activation carpten", "akt1 activation carpten et", "activation carpten et al.", "et al. 2007 landgraf", "al. 2007 landgraf et", "2007 landgraf et al.", "landgraf et al. 2008 ." ] }, { "record_id": "GLY_000594_1_482", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5676590", "r hsa", "hsa 5676590", "r hsa 5676590" ] }, { 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geijtenbeek &", "2009 geijtenbeek & gringhuis", "& gringhuis 2009 plato", "gringhuis 2009 plato et", "2009 plato et al.", "plato et al. 2013 ." ] }, { "record_id": "GLY_000594_1_483", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5676594", "r hsa", "hsa 5676594", "r hsa 5676594" ] }, { "record_id": "GLY_000594_1_483", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tnf receptor", "receptor superfamily", "members mediating", "mediating non", "non canonical", "canonical nf", "nf kb", "kb pathway", "tnf receptor superfamily", "superfamily tnfsf", "tnfsf members", "members mediating non", "mediating non canonical", "non canonical nf", "canonical nf kb", "nf kb pathway", "receptor superfamily tnfsf", "tnfsf members mediating", "members mediating non canonical", "mediating non canonical nf", "non canonical nf kb", "canonical nf kb pathway", "tnf receptor superfamily tnfsf", "superfamily tnfsf 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"al. 2002 cd40", "cd40 also known", "also known as tnfrsf5", "tnfrsf5 coope", "coope et al. 2002", "al. 2002 lymphotoxin", "2002 lymphotoxin beta", "beta receptor ltbr", "receptor ltbr also", "ltbr also known as", "also known as tnfrsf3", "tnfrsf3 dejardin", "dejardin et al. 2002", "2002 receptor", "receptor activator for nuclear", "activator for nuclear factor", "for nuclear factor kb", "factor kb rank", "kb rank also", "rank also known as", "also known as tnfrsf11a", "tnfrsf11a novack", "novack et al. 2003", "2003 cd27", "cd27 and fibroblast growth", "and fibroblast growth factor", "fibroblast growth factor inducible", "growth factor inducible immediate", "factor inducible immediate early", "inducible immediate early response", "immediate early response protein", "early response protein 14", "protein 14 fn14", "14 fn14 also", "fn14 also known as", "also known as tnfrsf12a", "as tnfrsf12a etc.", "tnfrsf12a etc. these", "etc. these receptors each", "these receptors each mediate", "receptors each mediate specific", "each mediate specific biological", "mediate specific biological roles", "specific biological roles of", "biological roles of the", "roles of the non", "of the non canonical", "the non canonical nf", "non canonical nf kb.", "canonical nf kb. these", "nf kb. these non", "kb. these non canonical", "these non canonical nf", "canonical nf kb stimulating", "nf kb stimulating receptors", "kb stimulating receptors have", "stimulating receptors have one", "receptors have one thing", "have one thing in", "one thing in common", "thing in common and", "in common and is", "common and is the", "and is the presence", "is the presence of", "the presence of a", "presence of a traf", "of a traf binding", "a traf binding motif", "binding motif which", "motif which recruits", "which recruits different tnf", "recruits different tnf receptor", "different tnf receptor associated", "tnf receptor associated factor", "associated factor traf", "members particularly traf2", "particularly traf2 and traf3", "and traf3 to", "traf3 to the", "to the receptor complex", "the receptor complex during", "receptor complex during ligand", "complex during ligand ligation", "ligand ligation grech", "ligation grech et", "grech et al. 2004", "al. 2004 bishop", "2004 bishop &", "bishop & xie 2007", "& xie 2007 .", "xie 2007 . receptor", "2007 . receptor recruitment", ". receptor recruitment of", "receptor recruitment of these", "recruitment of these traf", "of these traf members", "these traf members leads", "traf members leads to", "members leads to their", "leads to their degradation", "to their degradation which", "their degradation which is", "degradation which is a", "which is a critical", "is a critical step", "a critical step leading", "critical step leading to", "step leading to the", "leading to the activation", "to the activation of", "the activation of nik", "activation of nik and", "of nik and induction", "nik and induction of", "and induction of p100", "induction of p100 processing", "p100 processing sun", "processing sun 2011", "sun 2011 2012", "2011 2012 .", "activation of nf kb is", "of nf kb is fundamental", "nf kb is fundamental to", "kb is fundamental to signal", "is fundamental to signal transduction", "fundamental to signal transduction by", "to signal transduction by members", "signal transduction by members of", "transduction by members of the", "by members of the tnfrsf.", "members of the tnfrsf. expression", "of the tnfrsf. expression of", "the tnfrsf. expression of nf", "tnfrsf. expression of nf kb", "expression of nf kb target", "of nf kb target genes", "nf kb target genes is", "kb target genes is essential", "target genes is essential for", "genes is essential for mounting", "is essential for mounting innate", "essential for mounting innate immune", "for mounting innate immune responses", "mounting innate immune responses to", "innate immune responses to infectious", "immune responses to infectious microorganisms", "responses to infectious microorganisms but", "to infectious microorganisms but is", "infectious microorganisms but is also", "microorganisms but is also important", "but is also important for", "is also important for the", "also important for the proper", "important for the proper development", "for the proper development and", "the proper development and cellular", "proper development and cellular compartmentalization", "development and cellular compartmentalization of", "and cellular compartmentalization of secondary", "cellular compartmentalization of secondary lymphoid", "compartmentalization of secondary lymphoid organs", "of secondary lymphoid organs necessary", "secondary lymphoid organs necessary to", "lymphoid organs necessary to orchestrate", "organs necessary to orchestrate an", "necessary to orchestrate an adaptive", "to orchestrate an adaptive immune", "orchestrate an adaptive immune response.", "an adaptive immune response.
nf", "adaptive immune response.
nf kb", "immune response.
nf kb transcription", "response.
nf kb transcription factor", "
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activated by a", "be activated by a wide", "activated by a wide variety", "by a wide variety of", "a wide variety of receptors", "variety of receptors the", "of receptors the nf", "receptors the nf kb2", "the nf kb2 pathway is", "nf kb2 pathway is typically", "kb2 pathway is typically activated", "pathway is typically activated by", "is typically activated by a", "typically activated by a subset", "activated by a subset of", "by a subset of receptor", "a subset of receptor and", "subset of receptor and ligand", "of receptor and ligand pairs", "receptor and ligand pairs belonging", "and ligand pairs belonging to", "ligand pairs belonging to the", "pairs belonging to the tumor", "belonging to the tumor necrosis", "to the tumor necrosis factor", "the tumor necrosis factor receptor", "necrosis factor receptor tnf", "receptor tnf super", "family tnfrsf members.", "tnfrsf members. these members", "members. these members include tnfr2", "members include tnfr2 rauert", "include tnfr2 rauert et", "tnfr2 rauert et al.", "al. 2010 b", "2010 b cell", "b cell activating factor of", "cell activating factor of the", "activating factor of the tnf", "factor of the tnf family", "of the tnf family receptor", "tnf family receptor baffr", "family receptor baffr also", "receptor baffr also known", "baffr also known as tnfrsf13c", "as tnfrsf13c kayagaki", "tnfrsf13c kayagaki et", "et al. 2002 cd40", "2002 cd40 also", "cd40 also known as", "as tnfrsf5 coope", "tnfrsf5 coope et", "et al. 2002 lymphotoxin", "al. 2002 lymphotoxin beta", "2002 lymphotoxin beta receptor", "lymphotoxin beta receptor ltbr", "beta receptor ltbr also", "receptor ltbr also known", "ltbr also known as tnfrsf3", "as tnfrsf3 dejardin", "tnfrsf3 dejardin et", "al. 2002 receptor", "2002 receptor activator", "receptor activator for nuclear factor", "activator for nuclear factor kb", "nuclear factor kb rank", "factor kb rank also", "kb rank also known", "rank also known as tnfrsf11a", "as tnfrsf11a novack", "tnfrsf11a novack et", "al. 2003 cd27", "2003 cd27 and", "cd27 and fibroblast growth factor", "and fibroblast growth factor inducible", "fibroblast growth factor inducible immediate", "growth factor inducible immediate early", "factor inducible immediate early response", "inducible immediate early response protein", "immediate early response protein 14", "response protein 14 fn14", "protein 14 fn14 also", "14 fn14 also known", "fn14 also known as tnfrsf12a", "known as tnfrsf12a etc.", "as tnfrsf12a etc. these", "tnfrsf12a etc. these receptors", "etc. these receptors each mediate", "these receptors each mediate specific", "receptors each mediate specific biological", "each mediate specific biological roles", "mediate specific biological roles of", "specific biological roles of the", "biological roles of the non", "roles of the non canonical", "of the non canonical nf", "the non canonical nf kb.", "non canonical nf kb. these", "canonical nf kb. these non", "nf kb. these non canonical", "kb. these non canonical nf", "these non canonical nf kb", "non canonical nf kb stimulating", "canonical nf kb stimulating receptors", "nf kb stimulating receptors have", "kb stimulating receptors have one", "stimulating receptors have one thing", "receptors have one thing in", "have one thing in common", "one thing in common and", "thing in common and is", "in common and is the", "common and is the presence", "and is the presence of", "is the presence of a", "the presence of a traf", "presence of a traf binding", "of a traf binding motif", "traf binding motif which", "binding motif which recruits", "motif which recruits different", "which recruits different tnf receptor", "recruits different tnf receptor associated", "different tnf receptor associated factor", "receptor associated factor traf", "factor traf members", "traf members particularly", "members particularly traf2 and", "traf2 and traf3 to", "and traf3 to the", "traf3 to the receptor", "to the receptor complex during", "the receptor complex during ligand", "receptor complex during ligand ligation", "during ligand ligation grech", "ligand ligation grech et", "ligation grech et al.", "et al. 2004 bishop", "al. 2004 bishop &", "2004 bishop & xie", "bishop & xie 2007 .", "& xie 2007 . receptor", "xie 2007 . receptor recruitment", "2007 . receptor recruitment of", ". receptor recruitment of these", "receptor recruitment of these traf", "recruitment of these traf members", "of these traf members leads", "these traf members leads to", "traf members leads to their", "members leads to their degradation", "leads to their degradation which", "to their degradation which is", "their degradation which is a", "degradation which is a critical", "which is a critical step", "is a critical step leading", "a critical step leading to", "critical step leading to the", "step leading to the activation", "leading to the activation of", "to the activation of nik", "the activation of nik and", "activation of nik and induction", "of nik and induction of", "nik and induction of p100", "and induction of p100 processing", "of p100 processing sun", "p100 processing sun 2011", "sun 2011 2012 ." ] }, { "record_id": "GLY_000594_1_484", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5678895", "r hsa", "hsa 5678895", "r hsa 5678895" ] }, { "record_id": "GLY_000594_1_484", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cftr", "cftr causes", "causes cystic", "cystic fibrosis", "defective cftr causes", "cftr causes cystic", "causes cystic fibrosis", "defective cftr causes cystic", "cftr causes cystic fibrosis", "defective cftr causes cystic fibrosis", "fibrosis transmembrane", "transmembrane conductance", "conductance regulator", "is a", "a low", "low conductance", "conductance chloride", "chloride selective", "selective channel", "channel that", "that mediates", "mediates the", "the transport", "transport of", "of chloride", 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methylmalonic", "can cause methylmalonic aciduria", "cause methylmalonic aciduria and", "methylmalonic aciduria and homocystinuria", "and homocystinuria cblj", "homocystinuria cblj type", "cblj type mahcj", "mim:614857 a", "614857 a", "a genetically heterogeneous metabolic", "genetically heterogeneous metabolic disorder", "heterogeneous metabolic disorder of", "metabolic disorder of cbl", "disorder of cbl metabolism", "of cbl metabolism characterised", "cbl metabolism characterised by", "metabolism characterised by decreased", "characterised by decreased levels", "by decreased levels of", "decreased levels of the", "levels of the coenzymes", "of the coenzymes adenosylcobalamin", "coenzymes adenosylcobalamin adocbl", "adocbl and methylcobalamin", "and methylcobalamin mecbl", "methylcobalamin mecbl .", ". clinically symptoms", "clinically symptoms include", "symptoms include feeding difficulties", "feeding difficulties poor", "difficulties poor growth", "poor growth hypotonia", "lethargy anaemia and", "anaemia and delayed development", "delayed development coelho", "development coelho et", "coelho et al. 2012", "et al. 2012 .", "atp binding cassette sub family", "binding cassette sub family d", "cassette sub family d member", "sub family d member 4", "d member 4 abcd4", "4 abcd4 is", "abcd4 is thought to", "is thought to mediate the", "thought to mediate the lysosomal", "to mediate the lysosomal export", "mediate the lysosomal export of", "the lysosomal export of cobalamin", "export of cobalamin cbl", "of cobalamin cbl aka", "cobalamin cbl aka vitamin", "aka vitamin b12 into", "vitamin b12 into the", "b12 into the cytosol", "into the cytosol making", "the cytosol making it", "cytosol making it available", "making it available for the", "it available for the production", "available for the production of", "for the production of cbl", "the production of cbl cofactors.", "production of cbl cofactors. cbl", "of cbl cofactors. cbl is", "cbl cofactors. cbl is an", "cofactors. cbl is an important", "cbl is an important cofactor", "is an important cofactor for", "an important cofactor for correct", "important cofactor for correct haematological", "cofactor for correct haematological and", "for correct haematological and neurological", "correct haematological and neurological functions.", "haematological and neurological functions. defects", "and neurological functions. defects in", "neurological functions. defects in abcd4", "functions. defects in abcd4 can", "defects in abcd4 can cause", "in abcd4 can cause methylmalonic", "abcd4 can cause methylmalonic aciduria", "can cause methylmalonic aciduria and", "cause methylmalonic aciduria and homocystinuria", "aciduria and homocystinuria cblj", "and homocystinuria cblj type", "type mahcj mim:614857", "mim:614857 a genetically", "614857 a genetically", "a genetically heterogeneous metabolic disorder", "genetically heterogeneous metabolic disorder of", "heterogeneous metabolic disorder of cbl", "metabolic disorder of cbl metabolism", "disorder of cbl metabolism characterised", "of cbl metabolism characterised by", "cbl metabolism characterised by decreased", "metabolism characterised by decreased levels", "characterised by decreased levels of", "by decreased levels of the", "decreased levels of the coenzymes", "levels of the coenzymes adenosylcobalamin", "the coenzymes adenosylcobalamin adocbl", "adenosylcobalamin adocbl and", "and methylcobalamin mecbl .", "methylcobalamin mecbl . clinically", "mecbl . clinically symptoms", ". clinically symptoms include", "clinically symptoms include feeding", "include feeding difficulties poor", "feeding difficulties poor growth", "growth hypotonia lethargy", "hypotonia lethargy anaemia", "lethargy anaemia and delayed", "and delayed development coelho", "delayed development coelho et", "development coelho et al.", "coelho et al. 2012 ." ] }, { "record_id": "GLY_000594_1_486", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5684264", "r hsa", "hsa 5684264", "r hsa 5684264" ] }, { "record_id": "GLY_000594_1_486", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dependent mapk1/3", "mapk1/3 activation", "map3k8 tpl2", "tpl2 dependent", "dependent mapk1/3 activation", "tpl2 dependent mapk1/3", "map3k8 tpl2 dependent", "tpl2 dependent mapk1/3 activation", "tumor progression", "progression locus", "locus 2", "also known", "known as", "as cot", "cot and", "and map3k8", "functions as", "as a", "a mitogen", "mitogen activated", "activated protein", "protein kinase", "kinase kinase", "in various", "various stress", "stress responsive", "responsive signaling", "signaling cascades.", "cascades. map3k8", "mediates phosphorylation", "phosphorylation of", "of map2ks", "which in", "in turn", "turn phosphorylate", "phosphorylate mapk", "gantke t", "t et", "et al.", "2011 .

in", ".

in the", "the absence", "absence of", "of extra", "extra cellular", "cellular signals", "cytosolic map3k8", "is held", "held inactive", "inactive in", "in the", "the complex", "complex with", "with abin2", "and nfkb", "nfkb p105", "beinke s", "s et", "waterfield mr", "mr et", "lang v", "v et", "2004 .", ". this", "this interaction", "interaction stabilizes", "stabilizes map3k8", "but also", "also prevents", "prevents map3k8", "map3k8 and", "nfkb from", "from activating", "activating their", "their downstream", "downstream signaling", "signaling cascades", "cascades by", "by inhibiting", "inhibiting the", "the kinase", "kinase activity", "activity of", "of map3k8", "and the", "the proteolysis", "proteolysis of", "of nfkb", "nfkb precursor", "precursor protein", "protein p105.", "p105. upon", "upon activation", "activation of", "map3k8 by", "by various", "various stimuli", "such as", "as lps", "tnf alpha", "and il", "il 1", "1 beta", "ikbkb phosphorylates", "phosphorylates nfkb", "at ser927", "ser927 and", "and ser932", "which trigger", "trigger p105", "p105 proteasomal", "proteasomal degradation", "degradation and", "and releases", "releases map3k8", "map3k8 from", "from the", "roget k", "k et", "2012 .", ". simultaneously", "map3k8 is", "is activated", "activated by", "by auto", "and/or transphosphorylation", "al. 2011", "yang ht", "ht et", "al. 2012", ". the", "the released", "released active", "active map3k8", "map3k8 phosphorylates", "phosphorylates its", "its substrates", "map2ks. the", "the free", "free map3k8", "is also", "also unstable", "unstable and", "and is", "is targeted", "targeted for", "for proteasome", "proteasome mediated", "mediated degradation", "thus restricting", "restricting prolonged", "prolonged activation", "and its", "its downstream", "signaling pathways", "al. 2003", "cho j", "j et", "2005 .", ". furthermore", "partially degraded", "degraded nfkb", "into p50", "p50 can", "can dimerize", "dimerize with", "with other", "other nfkb", "nfkb family", "family members", "members to", "to regulate", "regulate the", "the transcription", "transcription of", "of target", "target genes.

map3k8", "genes.

map3k8 activity", "activity is", "is thought", "thought to", "the dynamics", "dynamics of", "of transcription", "transcription factors", "factors that", "that control", "control an", "an expression", "expression of", "of diverse", "diverse genes", "genes involved", "involved in", "in growth", "and inflammation.", "inflammation. suppressing", "suppressing the", "the map3k8", "map3k8 kinase", "activity with", "with selective", "selective inhibitors", "as c8", "c8 chloronaphthyridine", "chloronaphthyridine 3", "3 carbonitrile", "caused a", "a significant", "significant reduction", "reduction in", "in tnfalpha", "tnfalpha production", "production in", "in lps", "il 1beta", "1beta induced", "induced both", "both primary", "primary human", "human monocytes", "monocytes and", "and human", "human blood", "hall jp", "jp et", "al. 2007", "2007 .", ". similar", "similar results", "results have", "have been", "been reported", "reported for", "for mouse", "mouse lps", "lps stimulated", "stimulated raw264.7", "raw264.7 cells", "hirata k", "al. 2010", "2010 .", ". moreover", "stimulated macrophages", "macrophages derived", "derived from", "from map3k8", "map3k8 knockout", "knockout mice", "mice secreted", "secreted lower", "lower levels", "levels of", "of pro", "pro inflammatory", "inflammatory cytokines", "cytokines such", "as tnfalpha", "pge2 and", "and cxcl1", "dumitru cd", "cd et", "al. 2000", "eliopoulos ag", "ag et", "al. 2002", "2002 .", ". additionally", "bone marrow", "marrow derived", "derived dendritic", "dendritic cells", "and macrophages", "macrophages from", "mice showed", "showed significantly", "significantly lower", "lower expression", "of il", "1beta in", "in response", "response to", "to lps", "poly ic", "ic and", "and lps/mdp", "mielke et", "2009 .", ". however", "several other", "other studies", "studies seem", "seem to", "to contradict", "contradict these", "these findings", "findings and", "map3k8 deficiency", "deficiency in", "in mice", "mice has", "has been", "been also", "also reported", "reported to", "to enhance", "enhance pro", "inflammatory profiles.", "profiles. map3k8", "macrophages was", "was associated", "associated with", "with an", "an increase", "increase in", "in nitric", "nitric oxide", "oxide synthase", "synthase 2", "l\u00f3pez pel\u00e1ez", "pel\u00e1ez et", "2011 .", ". similarly", "of irak", "irak m", "whose function", "function is", "is to", "to compete", "compete with", "with il", "il 1r", "1r associated", "associated kinase", "family of", "of kinases", "was decreased", "decreased in", "in map3k8", "map3k8 /", "macrophages while", "while levels", "of tnf", "tnf and", "and il6", "il6 were", "were elevated", "zacharioudaki et", "significantly higher", "higher inflammation", "inflammation level", "level was", "was observed", "observed in", "in 12", "12 o", "o tetradecanoylphorbol", "tetradecanoylphorbol 13", "13 acetate", "treated map3k8", "mouse skin", "skin compared", "compared to", "to wt", "wt skin", "decicco skinner", "skinner k.", "k. et", "map3k8 activity", "is associated", "with nfkb", "nfkb inflammatory", "inflammatory pathway.", "pathway. high", "high levels", "of active", "active p65", "p65 nfkb", "nfkb were", "were observed", "the nucleus", "nucleus of", "mouse keratinocytes", "keratinocytes that", "that dramatically", "dramatically increased", "increased within", "within 15", "15 30", "30 minutes", "minutes of", "of tpa", "tpa treatment.", "treatment. similarly", "increased p65", "nfkb was", "map3k8 deficient", "deficient bmdc", "bmdc both", "both basally", "basally and", "and after", "after stimulation", "stimulation with", "with lps", "lps when", "when compared", "to wild", "wild type", "type controls", "the data", "data opposes", "opposes the", "the findings", "findings that", "that map3k8", "deficient mouse", "mouse embryo", "embryo fibroblasts", "fibroblasts and", "human jurkat", "jurkat t", "t cells", "cells with", "with kinase", "kinase domain", "domain deficient", "deficient protein", "protein have", "have a", "a reduction", "in nfkb", "nfkb activation", "activation but", "but only", "only when", "when certain", "certain stimuli", "stimuli are", "are administered", "lin et", "das s", ". thus", "it is", "is possible", "possible that", "that whether", "whether map3k8", "map3k8 serves", "serves more", "more of", "of a", "a pro", "inflammatory or", "or anti", "anti inflammatory", "inflammatory role", "role may", "may depend", "depend on", "on cell", "or tissue", "tissue type", "type and", "and on", "on stimuli", "lps vs.", "vs. tpa", "2012 .

map3k8", ".

map3k8 has", "also studied", "studied in", "the context", "context of", "of carcinogenesis", "however the", "the physiological", "physiological role", "role of", "map3k8 in", "the etiology", "etiology of", "of human", "human cancers", "cancers is", "also convoluted", "vougioukalaki m", "m et", "tumor progression locus", "progression locus 2", "2 tpl2", "tpl2 also", "also known as", "known as cot", "as cot and", "cot and map3k8", "map3k8 functions", "functions as a", "as a mitogen", "a mitogen activated", "mitogen activated protein", "activated protein kinase", "kinase mapk", "mapk kinase", "kinase map3k", "map3k in", "in various stress", "various stress responsive", "stress responsive signaling", "responsive signaling cascades.", "signaling cascades. map3k8", "tpl2 mediates", "mediates phosphorylation of", "phosphorylation of map2ks", "map2ks mek1/2", "mek1/2 which", "which in turn", "in turn phosphorylate", "turn phosphorylate mapk", "mapk erk1/2", "gantke t et", "t et al.", "2011 .

in the", ".

in the absence", "the absence of", "absence of extra", "of extra cellular", "extra cellular signals", "signals cytosolic", "tpl2 is", "is held inactive", "held inactive in", "inactive in the", "in the complex", "the complex with", "complex with abin2", "abin2 tnip2", "tnip2 and", "and nfkb p105", "p105 nfkb1", "beinke s et", "s et al.", "2003 waterfield", "waterfield mr et", "mr et al.", "2003 lang", "lang v et", "v et al.", "al. 2004", "2004 . this", ". this interaction", "this interaction stabilizes", "interaction stabilizes map3k8", "tpl2 but", "but also prevents", "also prevents map3k8", "prevents map3k8 and", "map3k8 and nfkb", "and nfkb from", "nfkb from activating", "from activating their", "activating their downstream", "their downstream signaling", "downstream signaling cascades", "signaling cascades by", "cascades by inhibiting", "by inhibiting the", "inhibiting the kinase", "the kinase activity", "kinase activity of", "activity of map3k8", "of map3k8 and", "map3k8 and the", "and the proteolysis", "the proteolysis of", "proteolysis of nfkb", "of nfkb precursor", "nfkb precursor protein", "precursor protein p105.", "protein p105. upon", "p105. upon activation", "upon activation of", "activation of map3k8", "of map3k8 by", "map3k8 by various", "by various stimuli", "stimuli such", "such as lps", "lps tnf", "alpha and", "and il 1", "il 1 beta", "ikbkb phosphorylates nfkb", "phosphorylates nfkb p105", "nfkb1 at", "at ser927 and", "ser927 and ser932", "ser932 which", "which trigger p105", "trigger p105 proteasomal", "p105 proteasomal degradation", "proteasomal degradation and", "degradation and releases", "and releases map3k8", "releases map3k8 from", "map3k8 from the", "from the complex", "complex beinke", "2003 2004", "2004 roget", "roget k et", "k et al.", "2012 . simultaneously", "simultaneously map3k8", "map3k8 is activated", "is activated by", "activated by auto", "auto and/or", "transphosphorylation gantke", "et al. 2011", "2011 yang", "yang ht et", "ht et al.", "et al. 2012", "al. 2012 .", "2012 . the", ". the released", "the released active", "released active map3k8", "active map3k8 phosphorylates", "map3k8 phosphorylates its", "phosphorylates its substrates", "substrates map2ks.", "map2ks. the free", "the free map3k8", "map3k8 however", "however is", "is also unstable", "also unstable and", "unstable and is", "and is targeted", "is targeted for", "targeted for proteasome", "for proteasome mediated", "proteasome mediated degradation", "degradation thus", "thus restricting prolonged", "restricting prolonged activation", "prolonged activation of", "tpl2 and", "and its downstream", "its downstream signaling", "downstream signaling pathways", "pathways waterfield", "et al. 2003", "2003 cho", "cho j et", "j et al.", "al. 2005", "2005 . furthermore", "furthermore partially", "partially degraded nfkb", "degraded nfkb p105", "nfkb1 into", "into p50 can", "p50 can dimerize", "can dimerize with", "dimerize with other", "with other nfkb", "other nfkb family", "nfkb family members", "family members to", "members to regulate", "to regulate the", "regulate the transcription", "the transcription of", "transcription of target", "of target genes.

map3k8", "target genes.

map3k8 activity", "genes.

map3k8 activity is", "activity is thought", "is thought to", "thought to regulate", "regulate the dynamics", "the dynamics of", "dynamics of transcription", "of transcription factors", "transcription factors that", "factors that control", "that control an", "control an expression", "an expression of", "expression of diverse", "of diverse genes", "diverse genes involved", "genes involved in", "involved in growth", "growth differentiation", "differentiation and", "and inflammation. suppressing", "inflammation. suppressing the", "suppressing the map3k8", "the map3k8 kinase", "map3k8 kinase activity", "kinase activity with", "activity with selective", "with selective inhibitors", "inhibitors such", "such as c8", "as c8 chloronaphthyridine", "c8 chloronaphthyridine 3", "chloronaphthyridine 3 carbonitrile", "carbonitrile caused", "caused a significant", "a significant reduction", "significant reduction in", "reduction in tnfalpha", "in tnfalpha production", "tnfalpha production in", "production in lps", "lps and", "and il 1beta", "il 1beta induced", "1beta induced both", "induced both primary", "both primary human", "primary human monocytes", "human monocytes and", "monocytes and human", "and human blood", "blood hall", "hall jp et", "jp et al.", "et al. 2007", "al. 2007 .", "2007 . similar", ". similar results", "similar results have", "results have been", "have been reported", "been reported for", "reported for mouse", "for mouse lps", "mouse lps stimulated", "lps stimulated raw264.7", "stimulated raw264.7 cells", "cells hirata", "hirata k et", "et al. 2010", "al. 2010 .", "2010 . moreover", "moreover lps", "lps stimulated macrophages", "stimulated macrophages derived", "macrophages derived from", "derived from map3k8", "from map3k8 knockout", "map3k8 knockout mice", "knockout mice secreted", "mice secreted lower", "secreted lower levels", "lower levels of", "levels of pro", "of pro inflammatory", "pro inflammatory cytokines", "inflammatory cytokines such", "cytokines such as", "such as tnfalpha", "tnfalpha cox2", "cox2 pge2", "pge2 and cxcl1", "cxcl1 dumitru", "dumitru cd et", "cd et al.", "et al. 2000", "2000 eliopoulos", "eliopoulos ag et", "ag et al.", "et al. 2002", "al. 2002 .", "2002 . additionally", "additionally bone", "bone marrow derived", "marrow derived dendritic", "derived dendritic cells", "cells bmdcs", "bmdcs and", "and macrophages from", "macrophages from map3k8", "knockout mice showed", "mice showed significantly", "showed significantly lower", "significantly lower expression", "lower expression of", "expression of il", "of il 1beta", "il 1beta in", "1beta in response", "in response to", "response to lps", "lps poly", "poly ic and", "ic and lps/mdp", "lps/mdp mielke", "mielke et al.", "al. 2009", "2009 . however", "however several", "several other studies", "other studies seem", "studies seem to", "seem to contradict", "to contradict these", "contradict these findings", "these findings and", "findings and map3k8", "and map3k8 deficiency", "map3k8 deficiency in", "deficiency in mice", "in mice has", "mice has been", "has been also", "been also reported", "also reported to", "reported to enhance", "to enhance pro", "enhance pro inflammatory", "pro inflammatory profiles.", "inflammatory profiles. map3k8", "profiles. map3k8 deficiency", "deficiency in lps", "in lps stimulated", "stimulated macrophages was", "macrophages was associated", "was associated with", "associated with an", "with an increase", "an increase in", "increase in nitric", "in nitric oxide", "nitric oxide synthase", "oxide synthase 2", "2 nos2", "nos2 expression", "expression l\u00f3pez", "l\u00f3pez pel\u00e1ez et", "pel\u00e1ez et al.", "2011 . similarly", "similarly expression", "expression of irak", "of irak m", "m whose", "whose function is", "function is to", "is to compete", "to compete with", "compete with il", "with il 1r", "il 1r associated", "1r associated kinase", "kinase irak", "irak family", "family of kinases", "kinases was", "was decreased in", "decreased in map3k8", "in map3k8 /", "/ macrophages", "macrophages while levels", "while levels of", "levels of tnf", "of tnf and", "tnf and il6", "and il6 were", "il6 were elevated", "elevated zacharioudaki", "zacharioudaki et al.", "2009 . moreover", "moreover significantly", "significantly higher inflammation", "higher inflammation level", "inflammation level was", "level was observed", "was observed in", "observed in 12", "in 12 o", "12 o tetradecanoylphorbol", "o tetradecanoylphorbol 13", "tetradecanoylphorbol 13 acetate", "acetate tpa", "tpa treated", "treated map3k8 /", "/ mouse", "mouse skin compared", "skin compared to", "compared to wt", "to wt skin", "skin decicco", "decicco skinner k.", "skinner k. et", "k. et al.", "2011 . additionally", "additionally map3k8", "map3k8 activity is", "activity is associated", "is associated with", "associated with nfkb", "with nfkb inflammatory", "nfkb inflammatory pathway.", "inflammatory pathway. high", "pathway. high levels", "high levels of", "levels of active", "of active p65", "active p65 nfkb", "p65 nfkb were", "nfkb were observed", "were observed in", "observed in the", "in the nucleus", "the nucleus of", "nucleus of map3k8", "mouse keratinocytes that", "keratinocytes that dramatically", "that dramatically increased", "dramatically increased within", "increased within 15", "within 15 30", "15 30 minutes", "30 minutes of", "minutes of tpa", "of tpa treatment.", "tpa treatment. similarly", "similarly increased", "increased p65 nfkb", "p65 nfkb was", "nfkb was observed", "observed in map3k8", "in map3k8 deficient", "map3k8 deficient bmdc", "deficient bmdc both", "bmdc both basally", "both basally and", "basally and after", "and after stimulation", "after stimulation with", "stimulation with lps", "with lps when", "lps when compared", "when compared to", "compared to wild", "to wild type", "wild type controls", "controls mielke", "2009 . the", ". the data", "the data opposes", "data opposes the", "opposes the findings", "the findings that", "findings that map3k8", "that map3k8 deficient", "map3k8 deficient mouse", "deficient mouse embryo", "mouse embryo fibroblasts", "embryo fibroblasts and", "fibroblasts and human", "and human jurkat", "human jurkat t", "jurkat t cells", "t cells with", "cells with kinase", "with kinase domain", "kinase domain deficient", "domain deficient protein", "deficient protein have", "protein have a", "have a reduction", "a reduction in", "reduction in nfkb", "in nfkb activation", "nfkb activation but", "activation but only", "but only when", "only when certain", "when certain stimuli", "certain stimuli are", "stimuli are administered", "administered lin", "lin et al.", "al. 1999", "1999 das", "das s et", "2005 . thus", "thus it", "it is possible", "is possible that", "possible that whether", "that whether map3k8", "whether map3k8 serves", "map3k8 serves more", "serves more of", "more of a", "of a pro", "a pro inflammatory", "pro inflammatory or", "inflammatory or anti", "or anti inflammatory", "anti inflammatory role", "inflammatory role may", "role may depend", "may depend on", "depend on cell", "cell or", "or tissue type", "tissue type and", "type and on", "and on stimuli", "stimuli lps", "lps vs. tpa", "tpa etc.", "2009 decicco", "2012 .

map3k8 has", ".

map3k8 has been", "been also studied", "also studied in", "studied in the", "in the context", "the context of", "context of carcinogenesis", "carcinogenesis however", "however the physiological", "the physiological role", "physiological role of", "role of map3k8", "of map3k8 in", "map3k8 in the", "in the etiology", "the etiology of", "etiology of human", "of human cancers", "human cancers is", "cancers is also", "is also convoluted", "convoluted vougioukalaki", "vougioukalaki m et", "m et al.", "2011 decicco", "tumor progression locus 2", "locus 2 tpl2", "tpl2 also known", "also known as cot", "known as cot and", "as cot and map3k8", "and map3k8 functions", "map3k8 functions as", "functions as a mitogen", "as a mitogen activated", "a mitogen activated protein", "mitogen activated protein kinase", "protein kinase mapk", "mapk kinase kinase", "kinase kinase map3k", "map3k in various", "in various stress responsive", "various stress responsive signaling", "stress responsive signaling cascades.", "responsive signaling cascades. map3k8", "cascades. map3k8 tpl2", "tpl2 mediates phosphorylation", "mediates phosphorylation of map2ks", "of map2ks mek1/2", "mek1/2 which in", "which in turn phosphorylate", "in turn phosphorylate mapk", "phosphorylate mapk erk1/2", "erk1/2 gantke", "gantke t et al.", "al. 2011 .

in", "2011 .

in the absence", ".

in the absence of", "the absence of extra", "absence of extra cellular", "of extra cellular signals", "cellular signals cytosolic", "signals cytosolic map3k8", "cytosolic map3k8 tpl2", "tpl2 is held", "is held inactive in", "held inactive in the", "inactive in the complex", "in the complex with", "the complex with abin2", "with abin2 tnip2", "tnip2 and nfkb", "nfkb p105 nfkb1", "nfkb1 beinke", "beinke s et al.", "2003 waterfield mr", "waterfield mr et al.", "2003 lang v", "lang v et al.", "et al. 2004", "al. 2004 .", "2004 . this interaction", ". this interaction stabilizes", "this interaction stabilizes map3k8", "stabilizes map3k8 tpl2", "tpl2 but also", "but also prevents map3k8", "also prevents map3k8 and", "prevents map3k8 and nfkb", "map3k8 and nfkb from", "and nfkb from activating", "nfkb from activating their", "from activating their downstream", "activating their downstream signaling", "their downstream signaling cascades", "downstream signaling cascades by", "signaling cascades by inhibiting", "cascades by inhibiting the", "by inhibiting the kinase", "inhibiting the kinase activity", "the kinase activity of", "kinase activity of map3k8", "activity of map3k8 and", "of map3k8 and the", "map3k8 and the proteolysis", "and the proteolysis of", "the proteolysis of nfkb", "proteolysis of nfkb precursor", "of nfkb precursor protein", "nfkb precursor protein p105.", "precursor protein p105. upon", "protein p105. upon activation", "p105. upon activation of", "upon activation of map3k8", "activation of map3k8 by", "of map3k8 by various", "map3k8 by various stimuli", "various stimuli such", "stimuli such as", "as lps tnf", "lps tnf alpha", "tnf alpha and", "alpha and il", "and il 1 beta", "beta ikbkb", "ikbkb phosphorylates nfkb p105", "nfkb1 at ser927", "at ser927 and ser932", "and ser932 which", "ser932 which trigger", "which trigger p105 proteasomal", "trigger p105 proteasomal degradation", "p105 proteasomal degradation and", "proteasomal degradation and releases", "degradation and releases map3k8", "and releases map3k8 from", "releases map3k8 from the", "map3k8 from the complex", "the complex beinke", "complex beinke s", "2004 roget k", "roget k et al.", ". simultaneously map3k8", "simultaneously map3k8 is", "map3k8 is activated by", "is activated by auto", "by auto and/or", "auto and/or transphosphorylation", "and/or transphosphorylation gantke", "transphosphorylation gantke t", "t et al. 2011", "al. 2011 yang", "2011 yang ht", "yang ht et al.", "ht et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the released", ". the released active", "the released active map3k8", "released active map3k8 phosphorylates", "active map3k8 phosphorylates its", "map3k8 phosphorylates its substrates", "its substrates map2ks.", "substrates map2ks. the", "map2ks. the free map3k8", "free map3k8 however", "however is also", "is also unstable and", "also unstable and is", "unstable and is targeted", "and is targeted for", "is targeted for proteasome", "targeted for proteasome mediated", "for proteasome mediated degradation", "mediated degradation thus", "degradation thus restricting", "thus restricting prolonged activation", "restricting prolonged activation of", "prolonged activation of map3k8", "of map3k8 tpl2", "tpl2 and its", "and its downstream signaling", "its downstream signaling pathways", "signaling pathways waterfield", "pathways waterfield mr", "mr et al. 2003", "al. 2003 cho", "2003 cho j", "cho j et al.", "et al. 2005", "al. 2005 .", ". furthermore partially", "furthermore partially degraded", "partially degraded nfkb p105", "nfkb1 into p50", "into p50 can dimerize", "p50 can dimerize with", "can dimerize with other", "dimerize with other nfkb", "with other nfkb family", "other nfkb family members", "nfkb family members to", "family members to regulate", "members to regulate the", "to regulate the transcription", "regulate the transcription of", "the transcription of target", "transcription of target genes.

map3k8", "of target genes.

map3k8 activity", "target genes.

map3k8 activity is", "genes.

map3k8 activity is thought", "activity is thought to", "is thought to regulate", "thought to regulate the", "to regulate the dynamics", "regulate the dynamics of", "the dynamics of transcription", "dynamics of transcription factors", "of transcription factors that", "transcription factors that control", "factors that control an", "that control an expression", "control an expression of", "an expression of diverse", "expression of diverse genes", "of diverse genes involved", "diverse genes involved in", "genes involved in growth", "in growth differentiation", "differentiation and inflammation.", "and inflammation. suppressing the", "inflammation. suppressing the map3k8", "suppressing the map3k8 kinase", "the map3k8 kinase activity", "map3k8 kinase activity with", "kinase activity with selective", "activity with selective inhibitors", "selective inhibitors such", "inhibitors such as", "such as c8 chloronaphthyridine", "as c8 chloronaphthyridine 3", "c8 chloronaphthyridine 3 carbonitrile", "3 carbonitrile caused", "carbonitrile caused a", "caused a significant reduction", "a significant reduction in", "significant reduction in tnfalpha", "reduction in tnfalpha production", "in tnfalpha production in", "tnfalpha production in lps", "in lps and", "lps and il", "and il 1beta induced", "il 1beta induced both", "1beta induced both primary", "induced both primary human", "both primary human monocytes", "primary human monocytes and", "human monocytes and human", "monocytes and human blood", "human blood hall", "blood hall jp", "hall jp et al.", "jp et al. 2007", "et al. 2007 .", "al. 2007 . similar", "2007 . similar results", ". similar results have", "similar results have been", "results have been reported", "have been reported for", "been reported for mouse", "reported for mouse lps", "for mouse lps stimulated", "mouse lps stimulated raw264.7", "lps stimulated raw264.7 cells", "raw264.7 cells hirata", "cells hirata k", "hirata k et al.", "k et al. 2010", "et al. 2010 .", "al. 2010 . moreover", ". moreover lps", "moreover lps stimulated", "lps stimulated macrophages derived", "stimulated macrophages derived from", "macrophages derived from map3k8", "derived from map3k8 knockout", "from map3k8 knockout mice", "map3k8 knockout mice secreted", "knockout mice secreted lower", "mice secreted lower levels", "secreted lower levels of", "lower levels of pro", "levels of pro inflammatory", "of pro inflammatory cytokines", "pro inflammatory cytokines such", "inflammatory cytokines such as", "cytokines such as tnfalpha", "as tnfalpha cox2", "cox2 pge2 and", "and cxcl1 dumitru", "cxcl1 dumitru cd", "dumitru cd et al.", "cd et al. 2000", "al. 2000 eliopoulos", "2000 eliopoulos ag", "eliopoulos ag et al.", "ag et al. 2002", "et al. 2002 .", "al. 2002 . additionally", ". additionally bone", "additionally bone marrow", "bone marrow derived dendritic", "marrow derived dendritic cells", "dendritic cells bmdcs", "bmdcs and macrophages", "and macrophages from map3k8", "macrophages from map3k8 knockout", "map3k8 knockout mice showed", "knockout mice showed significantly", "mice showed significantly lower", "showed significantly lower expression", "significantly lower expression of", "lower expression of il", "expression of il 1beta", "of il 1beta in", "il 1beta in response", "1beta in response to", "in response to lps", "to lps poly", "lps poly ic", "poly ic and lps/mdp", "and lps/mdp mielke", "lps/mdp mielke et", "et al. 2009", "al. 2009 .", ". however several", "however several other", "several other studies seem", "other studies seem to", "studies seem to contradict", "seem to contradict these", "to contradict these findings", "contradict these findings and", "these findings and map3k8", "findings and map3k8 deficiency", "and map3k8 deficiency in", "map3k8 deficiency in mice", "deficiency in mice has", "in mice has been", "mice has been also", "has been also reported", "been also reported to", "also reported to enhance", "reported to enhance pro", "to enhance pro inflammatory", "enhance pro inflammatory profiles.", "pro inflammatory profiles. map3k8", "inflammatory profiles. map3k8 deficiency", "profiles. map3k8 deficiency in", "map3k8 deficiency in lps", "deficiency in lps stimulated", "in lps stimulated macrophages", "lps stimulated macrophages was", "stimulated macrophages was associated", "macrophages was associated with", "was associated with an", "associated with an increase", "with an increase in", "an increase in nitric", "increase in nitric oxide", "in nitric oxide synthase", "nitric oxide synthase 2", "synthase 2 nos2", "expression l\u00f3pez pel\u00e1ez", "l\u00f3pez pel\u00e1ez et al.", "al. 2011 .", ". similarly expression", "similarly expression of", "expression of irak m", "irak m whose", "m whose function", "whose function is to", "function is to compete", "is to compete with", "to compete with il", "compete with il 1r", "with il 1r associated", "il 1r associated kinase", "associated kinase irak", "irak family of", "of kinases was", "kinases was decreased", "was decreased in map3k8", "decreased in map3k8 /", "map3k8 / macrophages", "/ macrophages while", "macrophages while levels of", "while levels of tnf", "levels of tnf and", "of tnf and il6", "tnf and il6 were", "and il6 were elevated", "were elevated zacharioudaki", "elevated zacharioudaki et", ". moreover significantly", "moreover significantly higher", "significantly higher inflammation level", "higher inflammation level was", "inflammation level was observed", "level was observed in", "was observed in 12", "observed in 12 o", "in 12 o tetradecanoylphorbol", "12 o tetradecanoylphorbol 13", "o tetradecanoylphorbol 13 acetate", "13 acetate tpa", "tpa treated map3k8", "map3k8 / mouse", "/ mouse skin", "mouse skin compared to", "skin compared to wt", "compared to wt skin", "wt skin decicco", "skin decicco skinner", "decicco skinner k. et", "skinner k. et al.", ". additionally map3k8", "additionally map3k8 activity", "map3k8 activity is associated", "activity is associated with", "is associated with nfkb", "associated with nfkb inflammatory", "with nfkb inflammatory pathway.", "nfkb inflammatory pathway. high", "inflammatory pathway. high levels", "pathway. high levels of", "high levels of active", "levels of active p65", "of active p65 nfkb", "active p65 nfkb were", "p65 nfkb were observed", "nfkb were observed in", "were observed in the", "observed in the nucleus", "in the nucleus of", "the nucleus of map3k8", "of map3k8 /", "/ mouse keratinocytes", "mouse keratinocytes that dramatically", "keratinocytes that dramatically increased", "that dramatically increased within", "dramatically increased within 15", "increased within 15 30", "within 15 30 minutes", "15 30 minutes of", "30 minutes of tpa", "minutes of tpa treatment.", "of tpa treatment. similarly", "treatment. similarly increased", "similarly increased p65", "increased p65 nfkb was", "p65 nfkb was observed", "nfkb was observed in", "was observed in map3k8", "observed in map3k8 deficient", "in map3k8 deficient bmdc", "map3k8 deficient bmdc both", "deficient bmdc both basally", "bmdc both basally and", "both basally and after", "basally and after stimulation", "and after stimulation with", "after stimulation with lps", "stimulation with lps when", "with lps when compared", "lps when compared to", "when compared to wild", "compared to wild type", "to wild type controls", "type controls mielke", "controls mielke et", "2009 . the data", ". the data opposes", "the data opposes the", "data opposes the findings", "opposes the findings that", "the findings that map3k8", "findings that map3k8 deficient", "that map3k8 deficient mouse", "map3k8 deficient mouse embryo", "deficient mouse embryo fibroblasts", "mouse embryo fibroblasts and", "embryo fibroblasts and human", "fibroblasts and human jurkat", "and human jurkat t", "human jurkat t cells", "jurkat t cells with", "t cells with kinase", "cells with kinase domain", "with kinase domain deficient", "kinase domain deficient protein", "domain deficient protein have", "deficient protein have a", "protein have a reduction", "have a reduction in", "a reduction in nfkb", "reduction in nfkb activation", "in nfkb activation but", "nfkb activation but only", "activation but only when", "but only when certain", "only when certain stimuli", "when certain stimuli are", "certain stimuli are administered", "are administered lin", "administered lin et", "et al. 1999", "1999 das s", "das s et al.", ". thus it", "thus it is", "it is possible that", "is possible that whether", "possible that whether map3k8", "that whether map3k8 serves", "whether map3k8 serves more", "map3k8 serves more of", "serves more of a", "more of a pro", "of a pro inflammatory", "a pro inflammatory or", "pro inflammatory or anti", "inflammatory or anti inflammatory", "or anti inflammatory role", "anti inflammatory role may", "inflammatory role may depend", "role may depend on", "may depend on cell", "on cell or", "cell or tissue", "or tissue type and", "tissue type and on", "type and on stimuli", "on stimuli lps", "stimuli lps vs.", "vs. tpa etc.", "etc. mielke", "2009 decicco skinner", "al. 2012 .

map3k8", "2012 .

map3k8 has been", ".

map3k8 has been also", "has been also studied", "been also studied in", "also studied in the", "studied in the context", "in the context of", "the context of carcinogenesis", "of carcinogenesis however", "carcinogenesis however the", "however the physiological role", "the physiological role of", "physiological role of map3k8", "role of map3k8 in", "of map3k8 in the", "map3k8 in the etiology", "in the etiology of", "the etiology of human", "etiology of human cancers", "of human cancers is", "human cancers is also", "cancers is also convoluted", "also convoluted vougioukalaki", "convoluted vougioukalaki m", "vougioukalaki m et al.", "2011 decicco skinner", "progression locus 2 tpl2", "2 tpl2 also", "tpl2 also known as", "also known as cot and", "known as cot and map3k8", "cot and map3k8 functions", "and map3k8 functions as", "map3k8 functions as a", "functions as a mitogen activated", "as a mitogen activated protein", "a mitogen activated protein kinase", "activated protein kinase mapk", "kinase mapk kinase", "kinase map3k in", "map3k in various stress", "in various stress responsive signaling", "various stress responsive signaling cascades.", "stress responsive signaling cascades. map3k8", "signaling cascades. map3k8 tpl2", "map3k8 tpl2 mediates", "tpl2 mediates phosphorylation of", "phosphorylation of map2ks mek1/2", "map2ks mek1/2 which", "mek1/2 which in turn", "which in turn phosphorylate mapk", "turn phosphorylate mapk erk1/2", "erk1/2 gantke t", "et al. 2011 .

in", "al. 2011 .

in the", "2011 .

in the absence of", ".

in the absence of extra", "the absence of extra cellular", "absence of extra cellular signals", "extra cellular signals cytosolic", "cellular signals cytosolic map3k8", "map3k8 tpl2 is", "tpl2 is held inactive", "is held inactive in the", "held inactive in the complex", "inactive in the complex with", "in the complex with abin2", "complex with abin2 tnip2", "abin2 tnip2 and", "tnip2 and nfkb p105", "and nfkb p105 nfkb1", "nfkb1 beinke s", "s et al. 2003", "al. 2003 waterfield", "2003 waterfield mr et", "al. 2003 lang", "2003 lang v et", "v et al. 2004", "et al. 2004 .", "al. 2004 . this", "2004 . this interaction stabilizes", ". this interaction stabilizes map3k8", "interaction stabilizes map3k8 tpl2", "map3k8 tpl2 but", "tpl2 but also prevents", "but also prevents map3k8 and", "also prevents map3k8 and nfkb", "prevents map3k8 and nfkb from", "map3k8 and nfkb from activating", "and nfkb from activating their", "nfkb from activating their downstream", "from activating their downstream signaling", "activating their downstream signaling cascades", "their downstream signaling cascades by", "downstream signaling cascades by inhibiting", "signaling cascades by inhibiting the", "cascades by inhibiting the kinase", "by inhibiting the kinase activity", "inhibiting the kinase activity of", "the kinase activity of map3k8", "kinase activity of map3k8 and", "activity of map3k8 and the", "of map3k8 and the proteolysis", "map3k8 and the proteolysis of", "and the proteolysis of nfkb", "the proteolysis of nfkb precursor", "proteolysis of nfkb precursor protein", "of nfkb precursor protein p105.", "nfkb precursor protein p105. upon", "precursor protein p105. upon activation", "protein p105. upon activation of", "p105. upon activation of map3k8", "upon activation of map3k8 by", "activation of map3k8 by various", "of map3k8 by various stimuli", "by various stimuli such", "various stimuli such as", "stimuli such as lps", "such as lps tnf", "as lps tnf alpha", "tnf alpha and il", "alpha and il 1", "1 beta ikbkb", "beta ikbkb phosphorylates", "phosphorylates nfkb p105 nfkb1", "p105 nfkb1 at", "nfkb1 at ser927 and", "ser927 and ser932 which", "and ser932 which trigger", "ser932 which trigger p105", "which trigger p105 proteasomal degradation", "trigger p105 proteasomal degradation and", "p105 proteasomal degradation and releases", "proteasomal degradation and releases map3k8", "degradation and releases map3k8 from", "and releases map3k8 from the", "releases map3k8 from the complex", "from the complex beinke", "the complex beinke s", "complex beinke s et", "al. 2003 2004", "2003 2004 roget", "2004 roget k et", "k et al. 2012", "al. 2012 . simultaneously", "2012 . simultaneously map3k8", ". simultaneously map3k8 is", "simultaneously map3k8 is activated", "map3k8 is activated by auto", "activated by auto and/or", "by auto and/or transphosphorylation", "and/or transphosphorylation gantke t", "transphosphorylation gantke t et", "gantke t et al. 2011", "et al. 2011 yang", "al. 2011 yang ht", "2011 yang ht et", "yang ht et al. 2012", "ht et al. 2012 .", "et al. 2012 . the", "al. 2012 . the released", "2012 . the released active", ". the released active map3k8", "the released active map3k8 phosphorylates", "released active map3k8 phosphorylates its", "active map3k8 phosphorylates its substrates", "phosphorylates its substrates map2ks.", "its substrates map2ks. the", "substrates map2ks. the free", "the free map3k8 however", "map3k8 however is", "however is also unstable", "is also unstable and is", "also unstable and is targeted", "unstable and is targeted for", "and is targeted for proteasome", "is targeted for proteasome mediated", "targeted for proteasome mediated degradation", "proteasome mediated degradation thus", "mediated degradation thus restricting", "degradation thus restricting prolonged", "thus restricting prolonged activation of", "restricting prolonged activation of map3k8", "activation of map3k8 tpl2", "map3k8 tpl2 and", "tpl2 and its downstream", "and its downstream signaling pathways", "downstream signaling pathways waterfield", "signaling pathways waterfield mr", "pathways waterfield mr et", "waterfield mr et al. 2003", "et al. 2003 cho", "al. 2003 cho j", "2003 cho j et", "j et al. 2005", "et al. 2005 .", "al. 2005 . furthermore", "2005 . furthermore partially", ". furthermore partially degraded", "furthermore partially degraded nfkb", "degraded nfkb p105 nfkb1", "p105 nfkb1 into", "nfkb1 into p50 can", "into p50 can dimerize with", "p50 can dimerize with other", "can dimerize with other nfkb", "dimerize with other nfkb family", "with other nfkb family members", "other nfkb family members to", "nfkb family members to regulate", "family members to regulate the", "members to regulate the transcription", "to regulate the transcription of", "regulate the transcription of target", "the transcription of target genes.

map3k8", "transcription of target genes.

map3k8 activity", "of target genes.

map3k8 activity is", "target genes.

map3k8 activity is thought", "genes.

map3k8 activity is thought to", "activity is thought to regulate", "is thought to regulate the", "thought to regulate the dynamics", "to regulate the dynamics of", "regulate the dynamics of transcription", "the dynamics of transcription factors", "dynamics of transcription factors that", "of transcription factors that control", "transcription factors that control an", "factors that control an expression", "that control an expression of", "control an expression of diverse", "an expression of diverse genes", "expression of diverse genes involved", "of diverse genes involved in", "diverse genes involved in growth", "involved in growth differentiation", "growth differentiation and", "differentiation and inflammation. suppressing", "and inflammation. suppressing the map3k8", "inflammation. suppressing the map3k8 kinase", "suppressing the map3k8 kinase activity", "the map3k8 kinase activity with", "map3k8 kinase activity with selective", "kinase activity with selective inhibitors", "with selective inhibitors such", "selective inhibitors such as", "inhibitors such as c8", "such as c8 chloronaphthyridine 3", "as c8 chloronaphthyridine 3 carbonitrile", "chloronaphthyridine 3 carbonitrile caused", "3 carbonitrile caused a", "carbonitrile caused a significant", "caused a significant reduction in", "a significant reduction in tnfalpha", "significant reduction in tnfalpha production", "reduction in tnfalpha production in", "in tnfalpha production in lps", "production in lps and", "in lps and il", "lps and il 1beta", "and il 1beta induced both", "il 1beta induced both primary", "1beta induced both primary human", "induced both primary human monocytes", "both primary human monocytes and", "primary human monocytes and human", "human monocytes and human blood", "and human blood hall", "human blood hall jp", "blood hall jp et", "hall jp et al. 2007", "jp et al. 2007 .", "et al. 2007 . similar", "al. 2007 . similar results", "2007 . similar results have", ". similar results have been", "similar results have been reported", "results have been reported for", "have been reported for mouse", "been reported for mouse lps", "reported for mouse lps stimulated", "for mouse lps stimulated raw264.7", "mouse lps stimulated raw264.7 cells", "stimulated raw264.7 cells hirata", "raw264.7 cells hirata k", "cells hirata k et", "hirata k et al. 2010", "k et al. 2010 .", "et al. 2010 . moreover", "2010 . moreover lps", ". moreover lps stimulated", "moreover lps stimulated macrophages", "lps stimulated macrophages derived from", "stimulated macrophages derived from map3k8", "macrophages derived from map3k8 knockout", "derived from map3k8 knockout mice", "from map3k8 knockout mice secreted", "map3k8 knockout mice secreted lower", "knockout mice secreted lower levels", "mice secreted lower levels of", "secreted lower levels of pro", "lower levels of pro inflammatory", "levels of pro inflammatory cytokines", "of pro inflammatory cytokines such", "pro inflammatory cytokines such as", "inflammatory cytokines such as tnfalpha", "such as tnfalpha cox2", "tnfalpha cox2 pge2", "cox2 pge2 and cxcl1", "pge2 and cxcl1 dumitru", "and cxcl1 dumitru cd", "cxcl1 dumitru cd et", "dumitru cd et al. 2000", "et al. 2000 eliopoulos", "al. 2000 eliopoulos ag", "2000 eliopoulos ag et", "eliopoulos ag et al. 2002", "ag et al. 2002 .", "et al. 2002 . additionally", "2002 . additionally bone", ". additionally bone marrow", "additionally bone marrow derived", "bone marrow derived dendritic cells", "derived dendritic cells bmdcs", "cells bmdcs and", "bmdcs and macrophages from", "and macrophages from map3k8 knockout", "macrophages from map3k8 knockout mice", "from map3k8 knockout mice showed", "map3k8 knockout mice showed significantly", "knockout mice showed significantly lower", "mice showed significantly lower expression", "showed significantly lower expression of", "significantly lower expression of il", "lower expression of il 1beta", "expression of il 1beta in", "of il 1beta in response", "il 1beta in response to", "1beta in response to lps", "response to lps poly", "to lps poly ic", "lps poly ic and", "ic and lps/mdp mielke", "and lps/mdp mielke et", "lps/mdp mielke et al.", "mielke et al. 2009", "et al. 2009 .", "al. 2009 . however", "2009 . however several", ". however several other", "however several other studies", "several other studies seem to", "other studies seem to contradict", "studies seem to contradict these", "seem to contradict these findings", "to contradict these findings and", "contradict these findings and map3k8", "these findings and map3k8 deficiency", "findings and map3k8 deficiency in", "and map3k8 deficiency in mice", "map3k8 deficiency in mice has", "deficiency in mice has been", "in mice has been also", "mice has been also reported", "has been also reported to", "been also reported to enhance", "also reported to enhance pro", "reported to enhance pro inflammatory", "to enhance pro inflammatory profiles.", "enhance pro inflammatory profiles. map3k8", "pro inflammatory profiles. map3k8 deficiency", "inflammatory profiles. map3k8 deficiency in", "profiles. map3k8 deficiency in lps", "map3k8 deficiency in lps stimulated", "deficiency in lps stimulated macrophages", "in lps stimulated macrophages was", "lps stimulated macrophages was associated", "stimulated macrophages was associated with", "macrophages was associated with an", "was associated with an increase", "associated with an increase in", "with an increase in nitric", "an increase in nitric oxide", "increase in nitric oxide synthase", "in nitric oxide synthase 2", "oxide synthase 2 nos2", "2 nos2 expression", "nos2 expression l\u00f3pez", "expression l\u00f3pez pel\u00e1ez et", "pel\u00e1ez et al. 2011", "et al. 2011 .", "al. 2011 . similarly", "2011 . similarly expression", ". similarly expression of", "similarly expression of irak", "of irak m whose", "irak m whose function", "m whose function is", "whose function is to compete", "function is to compete with", "is to compete with il", "to compete with il 1r", "compete with il 1r associated", "with il 1r associated kinase", "1r associated kinase irak", "kinase irak family", "irak family of kinases", "family of kinases was", "of kinases was decreased", "kinases was decreased in", "was decreased in map3k8 /", "in map3k8 / macrophages", "map3k8 / macrophages while", "/ macrophages while levels", "macrophages while levels of tnf", "while levels of tnf and", "levels of tnf and il6", "of tnf and il6 were", "tnf and il6 were elevated", "il6 were elevated zacharioudaki", "were elevated zacharioudaki et", "elevated zacharioudaki et al.", "zacharioudaki et al. 2009", "al. 2009 . moreover", "2009 . moreover significantly", ". moreover significantly higher", "moreover significantly higher inflammation", "significantly higher inflammation level was", "higher inflammation level was observed", "inflammation level was observed in", "level was observed in 12", "was observed in 12 o", "observed in 12 o tetradecanoylphorbol", "in 12 o tetradecanoylphorbol 13", "12 o tetradecanoylphorbol 13 acetate", "tetradecanoylphorbol 13 acetate tpa", "acetate tpa treated", "tpa treated map3k8 /", "treated map3k8 / mouse", "map3k8 / mouse skin", "/ mouse skin compared", "mouse skin compared to wt", "skin compared to wt skin", "to wt skin decicco", "wt skin decicco skinner", "skin decicco skinner k.", "decicco skinner k. et al.", "k. et al. 2011", "al. 2011 . additionally", "2011 . additionally map3k8", ". additionally map3k8 activity", "additionally map3k8 activity is", "map3k8 activity is associated with", "activity is associated with nfkb", "is associated with nfkb inflammatory", "associated with nfkb inflammatory pathway.", "with nfkb inflammatory pathway. high", "nfkb inflammatory pathway. high levels", "inflammatory pathway. high levels of", "pathway. high levels of active", "high levels of active p65", "levels of active p65 nfkb", "of active p65 nfkb were", "active p65 nfkb were observed", "p65 nfkb were observed in", "nfkb were observed in the", "were observed in the nucleus", "observed in the nucleus of", "in the nucleus of map3k8", "nucleus of map3k8 /", "/ mouse keratinocytes that", "mouse keratinocytes that dramatically increased", "keratinocytes that dramatically increased within", "that dramatically increased within 15", "dramatically increased within 15 30", "increased within 15 30 minutes", "within 15 30 minutes of", "15 30 minutes of tpa", "30 minutes of tpa treatment.", "minutes of tpa treatment. similarly", "tpa treatment. similarly increased", "treatment. similarly increased p65", "similarly increased p65 nfkb", "increased p65 nfkb was observed", "p65 nfkb was observed in", "nfkb was observed in map3k8", "was observed in map3k8 deficient", "observed in map3k8 deficient bmdc", "in map3k8 deficient bmdc both", "map3k8 deficient bmdc both basally", "deficient bmdc both basally and", "bmdc both basally and after", "both basally and after stimulation", "basally and after stimulation with", "and after stimulation with lps", "after stimulation with lps when", "stimulation with lps when compared", "with lps when compared to", "lps when compared to wild", "when compared to wild type", "compared to wild type controls", "wild type controls mielke", "type controls mielke et", "controls mielke et al.", "al. 2009 . the", "2009 . the data opposes", ". the data opposes the", "the data opposes the findings", "data opposes the findings that", "opposes the findings that map3k8", "the findings that map3k8 deficient", "findings that map3k8 deficient mouse", "that map3k8 deficient mouse embryo", "map3k8 deficient mouse embryo fibroblasts", "deficient mouse embryo fibroblasts and", "mouse embryo fibroblasts and human", "embryo fibroblasts and human jurkat", "fibroblasts and human jurkat t", "and human jurkat t cells", "human jurkat t cells with", "jurkat t cells with kinase", "t cells with kinase domain", "cells with kinase domain deficient", "with kinase domain deficient protein", "kinase domain deficient protein have", "domain deficient protein have a", "deficient protein have a reduction", "protein have a reduction in", "have a reduction in nfkb", "a reduction in nfkb activation", "reduction in nfkb activation but", "in nfkb activation but only", "nfkb activation but only when", "activation but only when certain", "but only when certain stimuli", "only when certain stimuli are", "when certain stimuli are administered", "stimuli are administered lin", "are administered lin et", "administered lin et al.", "lin et al. 1999", "al. 1999 das", "1999 das s et", "s et al. 2005", "al. 2005 . thus", "2005 . thus it", ". thus it is", "thus it is possible", "it is possible that whether", "is possible that whether map3k8", "possible that whether map3k8 serves", "that whether map3k8 serves more", "whether map3k8 serves more of", "map3k8 serves more of a", "serves more of a pro", "more of a pro inflammatory", "of a pro inflammatory or", "a pro inflammatory or anti", "pro inflammatory or anti inflammatory", "inflammatory or anti inflammatory role", "or anti inflammatory role may", "anti inflammatory role may depend", "inflammatory role may depend on", "role may depend on cell", "depend on cell or", "on cell or tissue", "cell or tissue type", "or tissue type and on", "tissue type and on stimuli", "and on stimuli lps", "on stimuli lps vs.", "stimuli lps vs. tpa", "lps vs. tpa etc.", "etc. mielke et", "al. 2009 decicco", "2009 decicco skinner k.", "k. et al. 2012", "et al. 2012 .

map3k8", "al. 2012 .

map3k8 has", "2012 .

map3k8 has been also", ".

map3k8 has been also studied", "has been also studied in", "been also studied in the", "also studied in the context", "studied in the context of", "in the context of carcinogenesis", "context of carcinogenesis however", "of carcinogenesis however the", "carcinogenesis however the physiological", "however the physiological role of", "the physiological role of map3k8", "physiological role of map3k8 in", "role of map3k8 in the", "of map3k8 in the etiology", "map3k8 in the etiology of", "in the etiology of human", "the etiology of human cancers", "etiology of human cancers is", "of human cancers is also", "human cancers is also convoluted", "is also convoluted vougioukalaki", "also convoluted vougioukalaki m", "convoluted vougioukalaki m et", "m et al. 2011", "al. 2011 decicco", "2011 decicco skinner k." ] }, { "record_id": "GLY_000594_1_487", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5685942", "r hsa", "hsa 5685942", "r hsa 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"in protein citrullination is involved", "protein citrullination is involved in", "citrullination is involved in disease", "is involved in disease pathophysiology", "in disease pathophysiology anzilotti", "disease pathophysiology anzilotti c", "pathophysiology anzilotti c et", "anzilotti c et al. 2010", "et al. 2010 sanchez", "al. 2010 sanchez pernaute", "2010 sanchez pernaute o", "sanchez pernaute o et al.", "pernaute o et al. 2013", "et al. 2013 sokolove", "al. 2013 sokolove j", "2013 sokolove j et", "sokolove j et al. 2011", "et al. 2011 sharma", "al. 2011 sharma p", "2011 sharma p et", "sharma p et al. 2012", "p et al. 2012 .", "et al. 2012 . citrullination", "al. 2012 . citrullination is", "2012 . citrullination is a", ". citrullination is a post", "citrullination is a post translational", "is a post translational modification", "a post translational modification event", "post translational modification event mediated", "translational modification event mediated by", "modification 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substrates by interactions", "their substrates by interactions of", "substrates by interactions of the", "by interactions of the variable", "interactions of the variable regions", "of the variable regions with", "the variable regions with the", "variable regions with the substrate", "regions with the substrate protein", "with the substrate protein directly", "substrate protein directly or", "protein directly or via", "directly or via scaffolds", "or via scaffolds or adapters", "via scaffolds or adapters in", "scaffolds or adapters in multiprotein", "or adapters in multiprotein complexes." ] }, { "record_id": "GLY_000594_1_492", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5689901", "r hsa", "hsa 5689901", "r hsa 5689901" ] }, { "record_id": "GLY_000594_1_492", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "metalloprotease dubs", "the jab1/mpn", "jab1/mpn +/mov34", "domain metalloproteases", 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jamm", "

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jamm", ".

jamm dub", "

jamm dub catalysis", "dub catalysis requires", "catalysis requires nucleophilic", "requires nucleophilic attack", "nucleophilic attack on", "attack on the", "on the carbonyl", "the carbonyl carbon", "carbonyl carbon of", "carbon of the", "of the isopeptide", "isopeptide bond by", "bond by an", "by an activated", "an activated water", "activated water molecule", "water molecule bound", "molecule bound to", "bound to zn2+", "to zn2+ and", "zn2+ and a", "and a conserved", "a conserved glutamate.", "conserved glutamate. a", "glutamate. a negatively", "a negatively charged", "negatively charged tetrahedral", "charged tetrahedral transition", "tetrahedral transition state", "transition state ensues", "ensues and", "and a nearby", "a nearby conserved", "nearby conserved ser/thr", "conserved ser/thr in", "ser/thr in the", "in the jamm", "the jamm domains", "jamm domains stabilizes", "domains stabilizes the", "stabilizes the oxyanion.", "the oxyanion. the", "oxyanion. the tetrahedral", "the tetrahedral intermediate", "tetrahedral intermediate then", "intermediate then collapses", "then collapses and", "collapses and the", "and the glu", "the glu serves", "glu serves as", "serves as a", "as a general", "a general base", "general base donating", "base donating a", "donating a proton", "a proton to", "proton to the", "to the leaving", "the leaving lys", "leaving lys side", "lys side chain", "chain ambroggio", "ambroggio et al.", "et al. 2004", "al. 2004 .", "jab1/mpn +/mov34 jamm", "jamm domain metalloproteases", "domain metalloproteases cleave the", "metalloproteases cleave the isopeptide", "cleave the isopeptide bond", "the isopeptide bond at", "isopeptide bond at or", "bond at or near", "at or near the", "or near the the", "near the the attachment", "the the attachment point", "the attachment point of", "attachment point of polyubiquitin", "point of polyubiquitin and", "of polyubiquitin and substrate.", "polyubiquitin and substrate. psmd14", "substrate. psmd14 rpn11", "rpn11 stambp", "amsh stambpl1", "stambpl1 amsh lp", "lp and", "and brcc3 brcc36", "brcc36 are highly", "are highly specific for", "highly specific for the", "specific for the k63", "for the k63 poly", "the k63 poly ub", "k63 poly ub linkage", "ub linkage which", "linkage which may", "which may be a", "may be a general", "be a general characteristic", "general characteristic eletr", "characteristic eletr &", "eletr & wilkinson 2014", "& wilkinson 2014 .", "wilkinson 2014 . two", "2014 . two multisubunit", ". two multisubunit complexes", "two multisubunit complexes represented", "multisubunit complexes represented elsewhere", "complexes represented elsewhere in", "represented elsewhere in reactome", "elsewhere in reactome contain", "in reactome contain jamm", "reactome contain jamm dubs.", "contain jamm dubs. the", "jamm dubs. the proteasome", "dubs. the proteasome 19s", "the proteasome 19s lid", "proteasome 19s lid complex", "19s lid complex includes", "lid complex includes psmd14", "includes psmd14 an", "psmd14 an endopeptidase", "an endopeptidase that cleaves", "endopeptidase that cleaves poly", "that cleaves poly ub", "cleaves poly ub chains", "poly ub chains from", "ub chains from substrates", "chains from substrates as", "from substrates as they", "substrates as they are", "as they are degraded", "they are degraded by", "are degraded by the", "degraded by the proteasome", "the proteasome verma", "proteasome verma et", "verma et al. 2002", "et al. 2002 .", "al. 2002 . the", "2002 . the cop9", ". the cop9 signalosome", "the cop9 signalosome contains", "cop9 signalosome contains cops5", "contains cops5 csn5", "csn5 which", "which deconjugates the ub", "deconjugates the ub like", "the ub like modifier", "ub like modifier nedd8", "modifier nedd8 modulating", "nedd8 modulating the", "modulating the activity of", "the activity of the", "activity of the scf", "of the scf e3", "the scf e3 ligase", "e3 ligase cope", "ligase cope et", "cope et al. 2002", "al. 2002 .

jamm", "2002 .

jamm dub", ".

jamm dub catalysis", "

jamm dub catalysis requires", "dub catalysis requires nucleophilic", "catalysis requires nucleophilic attack", "requires nucleophilic attack on", "nucleophilic attack on the", "attack on the carbonyl", "on the carbonyl carbon", "the carbonyl carbon of", "carbonyl carbon of the", "carbon of the isopeptide", "of the isopeptide bond", "the isopeptide bond by", "isopeptide bond by an", "bond by an activated", "by an activated water", "an activated water molecule", "activated water molecule bound", "water molecule bound to", "molecule bound to zn2+", "bound to zn2+ and", "to zn2+ and a", "zn2+ and a conserved", "and a conserved glutamate.", "a conserved glutamate. a", "conserved glutamate. a negatively", "glutamate. a negatively charged", "a negatively charged tetrahedral", "negatively charged tetrahedral transition", "charged tetrahedral transition state", "tetrahedral transition state ensues", "state ensues and", "ensues and a", "and a nearby conserved", "a nearby conserved ser/thr", "nearby conserved ser/thr in", "conserved ser/thr in the", "ser/thr in the jamm", "in the jamm domains", "the jamm domains stabilizes", "jamm domains stabilizes the", "domains stabilizes the oxyanion.", "stabilizes the oxyanion. the", "the oxyanion. the tetrahedral", "oxyanion. the tetrahedral intermediate", "the tetrahedral intermediate then", "tetrahedral intermediate then collapses", "intermediate then collapses and", "then collapses and the", "collapses and the glu", "and the glu serves", "the glu serves as", "glu serves as a", "serves as a general", "as a general base", "a general base donating", "general base donating a", "base donating a proton", "donating a proton to", "a proton to the", "proton to the leaving", "to the leaving lys", "the leaving lys side", "leaving lys side chain", "side chain ambroggio", "chain ambroggio et", "ambroggio et al. 2004", "et al. 2004 .", "the jab1/mpn +/mov34 jamm", "+/mov34 jamm domain", "jamm domain metalloproteases cleave", "domain metalloproteases cleave the isopeptide", "metalloproteases cleave the isopeptide bond", "cleave the isopeptide bond at", "the isopeptide bond at or", "isopeptide bond at or near", "bond at or near the", "at or near the the", "or near the the attachment", "near the the attachment point", "the the attachment point of", "the attachment point of polyubiquitin", "attachment point of polyubiquitin and", "point of polyubiquitin and substrate.", "of polyubiquitin and substrate. psmd14", "and substrate. psmd14 rpn11", "amsh lp and", "lp and brcc3", "brcc3 brcc36 are", "brcc36 are highly specific", "are highly specific for the", "highly specific for the k63", "specific for the k63 poly", "for the k63 poly ub", "the k63 poly ub linkage", "poly ub linkage which", "ub linkage which may", "linkage which may be", "which may be a general", "may be a general characteristic", "a general characteristic eletr", "general characteristic eletr &", "characteristic eletr & wilkinson", "eletr & wilkinson 2014 .", "& wilkinson 2014 . two", "wilkinson 2014 . two multisubunit", "2014 . two multisubunit complexes", ". two multisubunit complexes represented", "two multisubunit complexes represented elsewhere", "multisubunit complexes represented elsewhere in", "complexes represented elsewhere in reactome", "represented elsewhere in reactome contain", "elsewhere in reactome contain jamm", "in reactome contain jamm dubs.", "reactome contain jamm dubs. the", "contain jamm dubs. the proteasome", "jamm dubs. the proteasome 19s", "dubs. the proteasome 19s lid", "the proteasome 19s lid complex", "proteasome 19s lid complex includes", "19s lid complex includes psmd14", "complex includes psmd14 an", "includes psmd14 an endopeptidase", "psmd14 an endopeptidase that", "an endopeptidase that cleaves poly", "endopeptidase that cleaves poly ub", "that cleaves poly ub chains", "cleaves poly ub chains from", "poly ub chains from substrates", "ub chains from substrates as", "chains from substrates as they", "from substrates as they are", "substrates as they are degraded", "as they are degraded by", "they are degraded by the", "are degraded by the proteasome", "by the proteasome verma", "the proteasome verma et", "proteasome verma et al.", "verma et al. 2002 .", "et al. 2002 . the", "al. 2002 . the cop9", "2002 . the cop9 signalosome", ". the cop9 signalosome contains", "the cop9 signalosome contains cops5", "signalosome contains cops5 csn5", "csn5 which deconjugates", "which deconjugates the ub like", "deconjugates the ub like modifier", "the ub like modifier nedd8", "like modifier nedd8 modulating", "modifier nedd8 modulating the", "nedd8 modulating the activity", "modulating the activity of the", "the activity of the scf", "activity of the scf e3", "of the scf e3 ligase", "scf e3 ligase cope", "e3 ligase cope et", "ligase cope et al.", "cope et al. 2002 .", "et al. 2002 .

jamm", "al. 2002 .

jamm dub", "2002 .

jamm dub catalysis", ".

jamm dub catalysis requires", "

jamm dub catalysis requires nucleophilic", "dub catalysis requires nucleophilic attack", "catalysis requires nucleophilic attack on", "requires nucleophilic attack on the", "nucleophilic attack on the carbonyl", "attack on the carbonyl carbon", "on the carbonyl carbon of", "the carbonyl carbon of the", "carbonyl carbon of the isopeptide", "carbon of the isopeptide bond", "of the isopeptide bond by", "the isopeptide bond by an", "isopeptide bond by an activated", "bond by an activated water", "by an activated water molecule", "an activated water molecule bound", "activated water molecule bound to", "water molecule bound to zn2+", "molecule bound to zn2+ and", "bound to zn2+ and a", "to zn2+ and a conserved", "zn2+ and a conserved glutamate.", "and a conserved glutamate. a", "a conserved glutamate. a negatively", "conserved glutamate. a negatively charged", "glutamate. a negatively charged tetrahedral", "a negatively charged tetrahedral transition", "negatively charged tetrahedral transition state", "charged tetrahedral transition state ensues", "transition state ensues and", "state ensues and a", "ensues and a nearby", "and a nearby conserved ser/thr", "a nearby conserved ser/thr in", "nearby conserved ser/thr in the", "conserved ser/thr in the jamm", "ser/thr in the jamm domains", "in the jamm domains stabilizes", "the jamm domains stabilizes the", "jamm domains stabilizes the oxyanion.", "domains stabilizes the oxyanion. the", "stabilizes the oxyanion. the tetrahedral", "the oxyanion. the tetrahedral intermediate", "oxyanion. the tetrahedral intermediate then", "the tetrahedral intermediate then collapses", "tetrahedral intermediate then collapses and", "intermediate then collapses and the", "then collapses and the glu", "collapses and the glu serves", "and the glu serves as", "the glu serves as a", "glu serves as a general", "serves as a general base", "as a general base donating", "a general base donating a", "general base donating a proton", "base donating a proton to", "donating a proton to the", "a proton to the leaving", "proton to the leaving lys", "to the leaving lys side", "the leaving lys side chain", "lys side chain ambroggio", "side chain ambroggio et", "chain ambroggio et al.", "ambroggio et al. 2004 ." ] }, { "record_id": "GLY_000594_1_493", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5690714", "r hsa", "hsa 5690714", "r hsa 5690714" ] }, { "record_id": "GLY_000594_1_493", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cd22 mediated", "mediated bcr", "bcr regulation", "cd22 mediated bcr", "mediated bcr regulation", "cd22 mediated bcr regulation", "bcr activation", "activation is", "is highly", "highly regulated", "regulated and", "and coreceptors", "coreceptors like", "like cd22", "set a", "a signalling", "signalling threshold", "threshold to", "to prevent", "prevent aberrant", "aberrant immune", "immune response", "response and", "and autoimmune", "autoimmune disease", "cyster et", "et al.", "al. 1997", "han et", "al. 2005", "2005 .", ". cd22", "cd22 is", "is a", "a glycoprotein", "glycoprotein found", "found on", "on the", "the surface", "surface of", "of b", "b cells", "cells during", "during restricted", "restricted stages", "stages of", "of development.", "development. cd22", "a member", "member of", "of the", "the receptors", "receptors of", "the sialic", "sialic acid", "acid binding", "binding ig", "ig like", "like lectin", "family which", "which binds", "binds specifically", "specifically to", "to the", "the terminal", "terminal sequence", "sequence n", "n acetylneuraminic", "acetylneuraminic acid", "acid alpha", "alpha 2", "2 6", "neuac alpha", "present on", "on many", "many b", "b cell", "cell glycoproteins", "powell et", "al. 1993", "sgroi et", "1993 .", "cd22 has", "has seven", "seven immunoglobulin", "like extracellular", "extracellular domains", "domains and", "and a", "a cytoplasmic", "cytoplasmic tail", "tail containing", "containing six", "six tyrosines", "three of", "of which", "which belong", "belong to", "the inhibitory", "inhibitory immunoreceptor", "immunoreceptor tyrosine", "tyrosine based", "based inhibition", "inhibition motifs", "sequences. upon", "upon bcr", "bcr cross", "cross linking", "linking cd22", "is rapidly", "rapidly tyrosine", "tyrosine phosphorylated", "phosphorylated by", "by the", "the tyrosine", "tyrosine kinase", "kinase lyn", "thereby recruiting", "recruiting and", "and activating", "activating tyrosine", "tyrosine phosphatase", "shp 1", "1 and", "and inhibiting", "inhibiting calcium", "calcium signalling.", "bcr activation is", "activation is highly", "is highly regulated", "highly regulated and", "regulated and coreceptors", "and coreceptors like", "coreceptors like cd22", "cd22 siglec2", "siglec2 set", "set a signalling", "a signalling threshold", "signalling threshold to", "threshold to prevent", "to prevent aberrant", "prevent aberrant immune", "aberrant immune response", "immune response and", "response and autoimmune", "and autoimmune disease", "disease cyster", "cyster et al.", "et al. 1997", "1997 han", "han et al.", "et al. 2005", "al. 2005 .", "2005 . cd22", ". cd22 is", "cd22 is a", "is a glycoprotein", "a glycoprotein found", "glycoprotein found on", "found on the", "on the surface", "the surface of", "surface of b", "of b cells", "b cells during", "cells during restricted", "during restricted stages", "restricted stages of", "stages of development.", "of development. cd22", "development. cd22 is", "is a member", "a member of", "member of the", "of the receptors", "the receptors of", "receptors of the", "of the sialic", "the sialic acid", "sialic acid binding", "acid binding ig", "binding ig like", "ig like lectin", "lectin siglec", "siglec family", "family which binds", "which binds specifically", "binds specifically to", "specifically to the", "to the terminal", "the terminal sequence", "terminal sequence n", "sequence n acetylneuraminic", "n acetylneuraminic acid", "acetylneuraminic acid alpha", "acid alpha 2", "alpha 2 6", "6 galactose", "galactose neuac", "neuac alpha 2", "6 gal", "gal present", "present on many", "on many b", "many b cell", "b cell glycoproteins", "glycoproteins powell", "powell et al.", "et al. 1993", "1993 sgroi", "sgroi et al.", "al. 1993 .", "1993 . cd22", ". cd22 has", "cd22 has seven", "has seven immunoglobulin", "immunoglobulin ig", "like extracellular domains", "extracellular domains and", "domains and a", "and a cytoplasmic", "a cytoplasmic tail", "cytoplasmic tail containing", "tail containing six", "containing six tyrosines", "tyrosines three", "three of which", "of which belong", "which belong to", "belong to the", "to the inhibitory", "the inhibitory immunoreceptor", "inhibitory immunoreceptor tyrosine", "immunoreceptor tyrosine based", "tyrosine based inhibition", "based inhibition motifs", "motifs itims", "itims sequences.", "sequences. upon bcr", "upon bcr cross", "bcr cross linking", "cross linking cd22", "linking cd22 is", "cd22 is rapidly", "is rapidly tyrosine", "rapidly tyrosine phosphorylated", "tyrosine phosphorylated by", "phosphorylated by the", "by the tyrosine", "the tyrosine kinase", "tyrosine kinase lyn", "lyn thereby", "thereby recruiting and", "recruiting and activating", "and activating tyrosine", "activating tyrosine phosphatase", "phosphatase shp", "shp 1 and", "1 and inhibiting", "and inhibiting calcium", "inhibiting calcium signalling.", "bcr activation is highly", "activation is highly regulated", "is highly regulated and", "highly regulated and coreceptors", "regulated and coreceptors like", "and coreceptors like cd22", "like cd22 siglec2", "siglec2 set a", "set a signalling threshold", "a signalling threshold to", "signalling threshold to prevent", "threshold to prevent aberrant", "to prevent aberrant immune", "prevent aberrant immune response", "aberrant immune response and", "immune response and autoimmune", "response and autoimmune disease", "autoimmune disease cyster", "disease cyster et", "cyster et al. 1997", "al. 1997 han", "1997 han et", "han et al. 2005", "et al. 2005 .", "al. 2005 . cd22", "2005 . cd22 is", ". cd22 is a", "cd22 is a glycoprotein", "is a glycoprotein found", "a glycoprotein found on", "glycoprotein found on the", "found on the surface", "on the surface of", "the surface of b", "surface of b cells", "of b cells during", "b cells during restricted", "cells during restricted stages", "during restricted stages of", "restricted stages of development.", "stages of development. cd22", "of development. cd22 is", "development. cd22 is a", "cd22 is a member", "is a member of", "a member of the", "member of the receptors", "of the receptors of", "the receptors of the", "receptors of the sialic", "of the sialic acid", "the sialic acid binding", "sialic acid binding ig", "acid binding ig like", "binding ig like lectin", "like lectin siglec", "siglec family which", "family which 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"six tyrosines three", "tyrosines three of", "three of which belong", "of which belong to", "which belong to the", "belong to the inhibitory", "to the inhibitory immunoreceptor", "the inhibitory immunoreceptor tyrosine", "inhibitory immunoreceptor tyrosine based", "immunoreceptor tyrosine based inhibition", "tyrosine based inhibition motifs", "inhibition motifs itims", "itims sequences. upon", "sequences. upon bcr cross", "upon bcr cross linking", "bcr cross linking cd22", "cross linking cd22 is", "linking cd22 is rapidly", "cd22 is rapidly tyrosine", "is rapidly tyrosine phosphorylated", "rapidly tyrosine phosphorylated by", "tyrosine phosphorylated by the", "phosphorylated by the tyrosine", "by the tyrosine kinase", "the tyrosine kinase lyn", "kinase lyn thereby", "lyn thereby recruiting", "thereby recruiting and activating", "recruiting and activating tyrosine", "and activating tyrosine phosphatase", "tyrosine phosphatase shp", "phosphatase shp 1", "shp 1 and inhibiting", "1 and inhibiting calcium", "and inhibiting calcium signalling.", "bcr activation is highly regulated", "activation is highly regulated and", "is highly regulated and coreceptors", "highly regulated and coreceptors like", "regulated and coreceptors like cd22", "coreceptors like cd22 siglec2", "cd22 siglec2 set", "siglec2 set a signalling", "set a signalling threshold to", "a signalling threshold to prevent", "signalling threshold to prevent aberrant", "threshold to prevent aberrant immune", "to prevent aberrant immune response", "prevent aberrant immune response and", "aberrant immune response and autoimmune", "immune response and autoimmune disease", "and autoimmune disease cyster", "autoimmune disease cyster et", "disease cyster et al.", "et al. 1997 han", "al. 1997 han et", "1997 han et al.", "han et al. 2005 .", "et al. 2005 . cd22", "al. 2005 . cd22 is", "2005 . cd22 is a", ". cd22 is a glycoprotein", "cd22 is a glycoprotein found", "is a glycoprotein found on", "a glycoprotein found on the", "glycoprotein found on the surface", "found on the surface of", "on the surface of b", "the surface of b cells", "surface of b cells during", "of b cells during restricted", "b cells during restricted stages", "cells during restricted stages of", "during restricted stages of development.", "restricted stages of development. cd22", "stages of development. cd22 is", "of development. cd22 is a", "development. cd22 is a member", "cd22 is a member of", "is a member of the", "a member of the receptors", "member of the receptors of", "of the receptors of the", "the receptors of the sialic", "receptors of the sialic acid", "of the sialic acid binding", "the sialic acid binding ig", "sialic acid binding ig like", "acid binding ig like lectin", "ig like lectin siglec", "lectin siglec family", "siglec family which binds", "family which binds specifically to", "which binds specifically to the", "binds specifically to the terminal", "specifically to the terminal sequence", "to the terminal sequence n", "the terminal sequence n acetylneuraminic", "terminal sequence n acetylneuraminic acid", "sequence n acetylneuraminic acid alpha", "n acetylneuraminic acid alpha 2", "acetylneuraminic acid alpha 2 6", "alpha 2 6 galactose", "6 galactose neuac", "galactose neuac alpha 2", "alpha 2 6 gal", "6 gal present", "gal present on many", "present on many b cell", "on many b cell glycoproteins", "b cell glycoproteins powell", "cell glycoproteins powell et", "glycoproteins powell et al.", "et al. 1993 sgroi", "al. 1993 sgroi et", "1993 sgroi et al.", "sgroi et al. 1993 .", "et al. 1993 . cd22", "al. 1993 . cd22 has", "1993 . cd22 has seven", ". cd22 has seven immunoglobulin", "has seven immunoglobulin ig", "immunoglobulin ig like", "ig like extracellular domains", "like extracellular domains and a", "extracellular domains and a cytoplasmic", "domains and a cytoplasmic tail", "and a cytoplasmic tail containing", "a cytoplasmic tail containing six", "cytoplasmic tail containing six tyrosines", "containing six tyrosines three", "six tyrosines three of", "tyrosines three of which", "three of which belong to", "of which belong to the", "which belong to the inhibitory", "belong to the inhibitory immunoreceptor", "to the inhibitory immunoreceptor tyrosine", "the inhibitory immunoreceptor tyrosine based", "inhibitory immunoreceptor tyrosine based inhibition", "immunoreceptor tyrosine based inhibition motifs", "based inhibition motifs itims", "motifs itims sequences.", "itims sequences. upon bcr", "sequences. upon bcr cross linking", "upon bcr cross linking cd22", "bcr cross linking cd22 is", "cross linking cd22 is rapidly", "linking cd22 is rapidly tyrosine", "cd22 is rapidly tyrosine phosphorylated", "is rapidly tyrosine phosphorylated by", "rapidly tyrosine phosphorylated by the", "tyrosine phosphorylated by the tyrosine", "phosphorylated by the tyrosine kinase", "by the tyrosine kinase lyn", "tyrosine kinase lyn thereby", "kinase lyn thereby recruiting", "lyn thereby recruiting and", "thereby recruiting and activating tyrosine", "recruiting and activating tyrosine phosphatase", "activating tyrosine phosphatase shp", "tyrosine phosphatase shp 1", "phosphatase shp 1 and", "shp 1 and inhibiting calcium", "1 and inhibiting calcium signalling." ] }, { "record_id": "GLY_000594_1_494", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5693537", "r hsa", "hsa 5693537", "r hsa 5693537" ] }, { "record_id": "GLY_000594_1_494", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of d", "d loop", "loop structures", "resolution of d", "of d loop", "d loop structures", "resolution of d loop", "of d loop structures", "resolution of d loop structures", "once repair", "repair synthesis", "synthesis has", "has occurred", "the d", "loop structure", "structure may", "may be", "be resolved", "resolved either", "either through", "through holliday", "holliday 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mitchel", "mitchel et al.", "et al. 2010", "al. 2010 .", "2010 . sdsa", ". sdsa is", "sdsa is promoted", "is promoted by", "promoted by the", "by the dna", "the dna helicase", "dna helicase rtel1", "rtel1 barber", "barber et al.", "et al. 2008", "2008 uringa", "uringa et al.", "et al. 2012", "al. 2012 .", "2012 . additional", ". additional dna", "additional dna synthesis", "dna synthesis occurs", "synthesis occurs to", "occurs to fill", "to fill the", "fill the remaining", "the remaining single", "remaining single strand", "single strand gap", "strand gap present", "gap present in", "present in the", "in the reannealed", "the reannealed dna", "reannealed dna duplex.", "dna duplex. dna", "duplex. dna polymerase", "dna polymerase alpha", "polymerase alpha has", "alpha has been", "has been implicated", "been implicated in", "implicated in this", "in this late", "this late step", "late step of", "step of dna", "of dna repair", "synthesis levy", "levy et al.", "et al. 2009", "although rtel1 mediated", "rtel1 mediated recruitment", "mediated recruitment of", "recruitment of pcna", "of pcna bound", "pcna bound dna", "bound dna polymerases", "dna polymerases may", "polymerases may also", "may also be", "also be involved", "involved vannier", "vannier et al.", "et al. 2013", "al. 2013 .", "2013 . the", ". the remaining", "single strand nicks", "strand nicks are", "nicks are closed", "are closed by", "closed by dna", "by dna ligases", "ligases possibly", "possibly lig1 or", "lig1 or lig3", "lig3 mortusewicz", "mortusewicz et al.", "et al. 2006", "2006 puebla", "puebla osorio et", "osorio et al.", "al. 2006 .", "in the synthesis dependent", "the synthesis dependent strand", "sdsa model of", "model of d loop", "of d loop resolution", "loop resolution d", "resolution d loop", "d loop strands extended", "loop strands extended by", "strands extended by dna", "extended by dna repair", "by dna repair synthesis", "dna repair synthesis dissociate", "repair synthesis dissociate from", "synthesis dissociate from their", "dissociate from their sister", "from their sister chromatid", "their sister chromatid complements", "sister chromatid complements and", "chromatid complements and reanneal", "complements and reanneal with", "and reanneal with their", "reanneal with their original", "with their original complementary", "their original complementary strands", "complementary strands resulting", "strands resulting in", "resulting in non crossover", "in non crossover products", "crossover products mitchel", "products mitchel et", "mitchel et al. 2010", "et al. 2010 .", "al. 2010 . sdsa", "2010 . sdsa is", ". sdsa is promoted", "sdsa is promoted by", "is promoted by the", "promoted by the dna", "by the dna helicase", "the dna helicase rtel1", "helicase rtel1 barber", "rtel1 barber et", "barber et al. 2008", "al. 2008 uringa", "2008 uringa et", "uringa et al. 2012", "et al. 2012 .", "al. 2012 . additional", "2012 . additional dna", ". additional dna synthesis", "additional 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polymerases", "bound dna polymerases may", "dna polymerases may also", "polymerases may also be", "may also be involved", "be involved vannier", "involved vannier et", "vannier et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the remaining", ". the remaining single", "remaining single strand nicks", "single strand nicks are", "strand nicks are closed", "nicks are closed by", "are closed by dna", "closed by dna ligases", "dna ligases possibly", "ligases possibly lig1", "possibly lig1 or lig3", "or lig3 mortusewicz", "lig3 mortusewicz et", "mortusewicz et al. 2006", "al. 2006 puebla", "2006 puebla osorio", "puebla osorio et al.", "osorio et al. 2006", "et al. 2006 .", "in the synthesis dependent strand", "the synthesis dependent strand annealing", "annealing sdsa model", "sdsa model of d", "model of d loop resolution", "d loop resolution d", "loop resolution d loop", "resolution d loop strands", "d loop strands extended by", "loop strands extended by dna", "strands extended by 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the dna", "promoted by the dna helicase", "by the dna helicase rtel1", "dna helicase rtel1 barber", "helicase rtel1 barber et", "rtel1 barber et al.", "et al. 2008 uringa", "al. 2008 uringa et", "2008 uringa et al.", "uringa et al. 2012 .", "et al. 2012 . additional", "al. 2012 . additional dna", "2012 . additional dna synthesis", ". additional dna synthesis occurs", "additional dna synthesis occurs to", "dna synthesis occurs to fill", "synthesis occurs to fill the", "occurs to fill the remaining", "to fill the remaining single", "fill the remaining single strand", "the remaining single strand gap", "remaining single strand gap present", "single strand gap present in", "strand gap present in the", "gap present in the reannealed", "present in the reannealed dna", "in the reannealed dna duplex.", "the reannealed dna duplex. dna", "reannealed dna duplex. dna polymerase", "dna duplex. dna polymerase alpha", "duplex. dna polymerase alpha has", "dna polymerase alpha has been", "polymerase alpha has been implicated", "alpha has been implicated in", "has been implicated in this", "been implicated in this late", "implicated in this late step", "in this late step of", "this late step of dna", "late step of dna repair", "step of dna repair synthesis", "dna repair synthesis levy", "repair synthesis levy et", "synthesis levy et al.", "al. 2009 although", "2009 although rtel1", "although rtel1 mediated recruitment of", "rtel1 mediated recruitment of pcna", "mediated recruitment of pcna bound", "recruitment of pcna bound dna", "of pcna bound dna polymerases", "pcna bound dna polymerases may", "bound dna polymerases may also", "dna polymerases may also be", "polymerases may also be involved", "also be involved vannier", "be involved vannier et", "involved vannier et al.", "vannier et al. 2013 .", "et al. 2013 . the", "al. 2013 . the remaining", "2013 . the remaining single", ". the remaining single strand", "the remaining single strand nicks", "remaining single strand nicks are", "single strand nicks are closed", "strand nicks are closed by", "nicks are closed by dna", "are closed by dna ligases", "by dna ligases possibly", "dna ligases possibly lig1", "ligases possibly lig1 or", "lig1 or lig3 mortusewicz", "or lig3 mortusewicz et", "lig3 mortusewicz et al.", "et al. 2006 puebla", "al. 2006 puebla osorio", "2006 puebla osorio et", "puebla osorio et al. 2006", "osorio et al. 2006 ." ] }, { "record_id": "GLY_000594_1_496", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5693565", "r hsa", "hsa 5693565", "r hsa 5693565" ] }, { "record_id": "GLY_000594_1_496", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "recruitment and", "and atm", "atm mediated", "mediated phosphorylation", "phosphorylation of", "of repair", "repair and", "and signaling", "signaling proteins", "proteins at", "at dna", "dna double", "double strand", "strand breaks", "recruitment and atm", "and atm 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"proteins at dna double strand", "at dna double strand breaks", "activated atm", "atm phosphorylates", "phosphorylates a", "a number", "number of", "of proteins", "proteins involved", "involved in", "in the", "the dna", "dna damage", "damage checkpoint", "checkpoint and", "and dna", "dna repair", "thompson and", "and schild", "schild 2002", "ciccia and", "and elledge", "elledge 2010", "thereby triggering", "triggering and", "and coordinating", "coordinating accumulation", "accumulation of", "of dna", "dna dsb", "dsb repair", "repair proteins", "proteins in", "in nuclear", "nuclear foci", "foci known", "known as", "as ionizing", "ionizing radiation", "radiation induced", "induced foci", "irif .", ". while", "while irifs", "irifs include", "include chromatin", "chromatin regions", "regions kilobases", "kilobases away", "away from", "from the", "the actual", "actual dsb", "dsb site", "this reactome", "reactome pathway", "pathway represents", "represents simplified", "simplified foci", "foci and", "and events", "events that", "that happen", "happen proximal", "proximal to", "to the", "dsb ends.", "ends. in", "in general", "proteins localizing", "localizing to", "the nuclear", "foci in", "in response", "response to", "to atm", "atm signaling", "signaling are", "are cooperatively", "cooperatively retained", "retained at", "at the", "forming a", "a positive", "positive feedback", "feedback loop", "loop and", "and amplifying", "amplifying dna", "damage response", "soutoglou and", "and misteli", "misteli 2008", "2008 .

activated", ".

activated atm", "phosphorylates the", "the nbn", "subunit of", "of the", "the mrn", "mrn complex", "gatei et", "et al.", "al. 2000", "as well", "well as", "as the", "the nucleosome", "nucleosome histone", "histone h2afx", "on serine", "serine residue", "residue s139", "producing gamma", "gamma h2afx", "gamma h2ax", "containing nucleosomes", "rogakou et", "al. 1998", "burma et", "al. 2001", "2001 .", ". h2afx", "h2afx is", "is phosphorylated", "phosphorylated on", "on tyrosine", "tyrosine 142", "under basal", "basal conditions", "xiao et", "al. 2009", "2009 .", ". after", "after atm", "of h2afx", "h2afx on", "on s139", "tyrosine y142", "y142 has", "has to", "to be", "be dephosphorylated", "dephosphorylated by", "by eya", "eya family", "family phosphatases", "phosphatases in", "in order", "order for", "for the", "repair to", "to proceed", "proceed and", "and to", "to avoid", "avoid apoptosis", "apoptosis induced", "induced by", "by dna", "dna dsbs", "cook et", ". gamma", "h2afx recruits", "recruits mdc1", "mdc1 to", "to dna", "stucki et", "al. 2005", "2005 .", "phosphorylates mdc1", "liu et", "al. 2012", "h2afx nucleosomes", "and mdc1", "mdc1 serve", "serve as", "as a", "a core", "core of", "nuclear focus", "focus and", "and a", "a platform", "platform for", "the recruitment", "recruitment of", "of other", "other proteins", "in dna", "damage signaling", "signaling and", "and repair", "lukas et", "al. 2004", "2008 .

rnf8", ".

rnf8 ubiquitin", "ubiquitin ligase", "ligase binds", "binds phosphorylated", "phosphorylated mdc1", "kolas et", "al. 2007", "in cooperation", "cooperation with", "with herc2", "herc2 and", "and rnf168", "bekker jensen", "jensen et", "al. 2010", "campbell et", "ubiquitinates h2afx", "mailand et", "huen et", "stewart et", "doil et", "and histone", "histone demethylases", "demethylases kdm4a", "kdm4a and", "and kdm4b", "mallette et", "2012 .

ubiquitinated", ".

ubiquitinated gamma", "recruits uimc1", "promoting the", "the assembly", "assembly of", "the brca1", "brca1 a", "a complex", "complex at", "dna dsbs.", "dsbs. the", "complex consists", "consists of", "of rap80", "brca1:bard1 heterodimer", "and babam1", "wang et", "wang and", "elledge 2007", "2007

ubiquitin", "

ubiquitin mediated", "mediated degradation", "degradation of", "of kdm4a", "kdm4b allows", "allows tp53bp1", "to associate", "associate with", "with histone", "histone h4", "h4 dimethylated", "dimethylated on", "on lysine", "lysine k21", "h4k20me2 mark", "by whsc1", "whsc1 at", "dsb sites", "pei et", "al. 2011", "2011 .

once", ".

once recruited", "recruited to", "both brca1:bard1", "brca1:bard1 heterodimers", "heterodimers and", "and tp53bp1", "tp53bp1 are", "are phosphorylated", "phosphorylated by", "by atm", "cortez et", "al. 1999", "kim et", "al. 2006", "jowsey et", "which triggers", "triggers recruitment", "and activation", "activation of", "of chek2", "al. 2002", "wilson and", "and stern", "stern 2008", "melchionna et", "2000 .

depending", ".

depending on", "on the", "the cell", "cell cycle", "cycle stage", "brca1 and", "tp53bp1 competitively", "competitively promote", "promote either", "either homology", "homology directed", "directed repair", "or nonhomologous", "nonhomologous end", "end joining", "dsbs. hdr", "hdr through", "through homologous", "homologous recombination", "recombination repair", "or single", "single strand", "strand annealing", "is promoted", "promoted by", "by brca1", "brca1 in", "in association", "association with", "with rbbp8", "while nhej", "nhej is", "by tp53bp1", "tp53bp1 in", "with rif1", "escribano diaz", "diaz et", "al. 2013", "2013 .", "activated atm phosphorylates", "atm phosphorylates a", "phosphorylates a number", "a number of", "number of proteins", "of proteins involved", "proteins involved in", "involved in the", "in the dna", "the dna damage", "dna damage checkpoint", "damage checkpoint and", "checkpoint and dna", "and dna repair", "repair thompson", "thompson and schild", "and schild 2002", "2002 ciccia", "ciccia and elledge", "and elledge 2010", "thereby triggering and", "triggering and coordinating", "and coordinating accumulation", "coordinating accumulation of", "accumulation of dna", "of dna dsb", "dna dsb repair", "dsb repair proteins", "repair proteins in", "proteins in nuclear", "in nuclear foci", "nuclear foci known", "foci known as", "known as ionizing", "as ionizing radiation", "ionizing radiation induced", "radiation induced foci", "foci irif", "irif . while", ". while irifs", "while irifs include", "irifs include chromatin", "include chromatin regions", "chromatin regions kilobases", "regions kilobases away", "kilobases away from", "away from the", "from the actual", "the actual dsb", "actual dsb site", "site this", "this reactome pathway", "reactome pathway represents", "pathway represents simplified", "represents simplified foci", "simplified foci and", "foci and events", "and events that", "events that happen", "that happen proximal", "happen proximal to", "proximal to the", "to the dna", "the dna dsb", "dna dsb ends.", "dsb ends. in", "ends. in general", "general proteins", "proteins localizing to", "localizing to the", "to the nuclear", "the nuclear foci", "nuclear foci in", "foci in response", "in response to", "response to atm", "to atm signaling", "atm signaling are", "signaling are cooperatively", "are cooperatively retained", "cooperatively retained at", "retained at the", "at the dna", "dna dsb site", "site forming", "forming a positive", "a positive feedback", "positive feedback loop", "feedback loop and", "loop and amplifying", "and amplifying dna", "amplifying dna damage", "dna damage response", "response soutoglou", "soutoglou and misteli", "and misteli 2008", "misteli 2008 .

activated", "2008 .

activated atm", ".

activated atm phosphorylates", "atm phosphorylates the", "phosphorylates the nbn", "nbn nbs1", "nbs1 subunit", "subunit of the", "of the mrn", "the mrn complex", "complex mre11a:rad50:nbn", "gatei et al.", "et al. 2000", "as well as", "well as the", "as the nucleosome", "the nucleosome histone", "nucleosome histone h2afx", "h2afx h2ax", "h2ax on", "on serine residue", "serine residue s139", "s139 producing", "producing gamma h2afx", "h2afx gamma", "h2ax containing", "nucleosomes rogakou", "rogakou et al.", "et al. 1998", "1998 burma", "burma et al.", "et al. 2001", "al. 2001 .", "2001 . h2afx", ". h2afx is", "h2afx is phosphorylated", "is phosphorylated on", "phosphorylated on tyrosine", "on tyrosine 142", "142 y142", "y142 under", "under basal conditions", "conditions xiao", "xiao et al.", "et al. 2009", "al. 2009 .", "2009 . after", ". after atm", "after atm mediated", "phosphorylation of h2afx", "of h2afx on", "h2afx on s139", "s139 tyrosine", "tyrosine y142 has", "y142 has to", "has to be", "to be dephosphorylated", "be dephosphorylated by", "dephosphorylated by eya", "by eya family", "eya family phosphatases", "family phosphatases in", "phosphatases in order", "in order for", "order for the", "for the dna", "the dna repair", "dna repair to", "repair to proceed", "to proceed and", "proceed and to", "and to avoid", "to avoid apoptosis", "avoid apoptosis induced", "apoptosis induced by", "induced by dna", "by dna dsbs", "dsbs cook", "cook et al.", "2009 . gamma", ". gamma h2afx", "gamma h2afx recruits", "h2afx recruits mdc1", "recruits mdc1 to", "mdc1 to dna", "to dna dsbs", "dsbs stucki", "stucki et al.", "et al. 2005", "al. 2005 .", "2005 . after", "after atm phosphorylates", "atm phosphorylates mdc1", "mdc1 liu", "liu et al.", "et al. 2012", "complex gamma", "gamma h2afx nucleosomes", "nucleosomes and", "and mdc1 serve", "mdc1 serve as", "serve as a", "as a core", "a core of", "core of the", "of the nuclear", "the nuclear focus", "nuclear focus and", "focus and a", "and a platform", "a platform for", "platform for the", "for the recruitment", "the recruitment of", "recruitment of other", "of other proteins", "other proteins involved", "involved in dna", "in dna damage", "dna damage signaling", "damage signaling and", "signaling and repair", "repair lukas", "lukas et al.", "et al. 2004", "2004 soutoglou", "misteli 2008 .

rnf8", "2008 .

rnf8 ubiquitin", ".

rnf8 ubiquitin ligase", "ubiquitin ligase binds", "ligase binds phosphorylated", "binds phosphorylated mdc1", "mdc1 kolas", "kolas et al.", "et al. 2007", "2007 and", "and in", "in cooperation with", "cooperation with herc2", "with herc2 and", "herc2 and rnf168", "rnf168 bekker", "bekker jensen et", "jensen et al.", "et al. 2010", "2010 campbell", "campbell et al.", "h2afx mailand", "mailand et al.", "2007 huen", "huen et al.", "2007 stewart", "stewart et al.", "2009 doil", "doil et al.", "2009 and", "and histone demethylases", "histone demethylases kdm4a", "demethylases kdm4a and", "kdm4a and kdm4b", "kdm4b mallette", "mallette et al.", "al. 2012 .

ubiquitinated", "2012 .

ubiquitinated gamma", ".

ubiquitinated gamma h2afx", "h2afx recruits uimc1", "uimc1 rap80", "promoting the assembly", "the assembly of", "assembly of the", "of the brca1", "the brca1 a", "brca1 a complex", "a complex at", "complex at dna", "at dna dsbs.", "dna dsbs. the", "dsbs. the brca1", "a complex consists", "complex consists of", "consists of rap80", "rap80 fam175a", "fam175a abraxas", "heterodimer brcc3", "brcc3 brcc36", "bre brcc45", "brcc45 and", "babam1 merit40", "merit40 nba1", "wang et al.", "2007 wang", "wang and elledge", "and elledge 2007", "elledge 2007

ubiquitin", "2007

ubiquitin mediated", "

ubiquitin mediated degradation", "mediated degradation of", "degradation of kdm4a", "of kdm4a and", "and kdm4b allows", "kdm4b allows tp53bp1", "tp53bp1 53bp1", "53bp1 to", "to associate with", "associate with histone", "with histone h4", "histone h4 dimethylated", "h4 dimethylated on", "dimethylated on lysine", "on lysine k21", "k21 h4k20me2", "mark by", "by whsc1 at", "whsc1 at dna", "at dna dsb", "dna dsb sites", "sites pei", "pei et al.", "et al. 2011", "al. 2011 .

once", "2011 .

once recruited", ".

once recruited to", "recruited to dna", "dsbs both", "both brca1:bard1 heterodimers", "brca1:bard1 heterodimers and", "heterodimers and tp53bp1", "and tp53bp1 are", "tp53bp1 are phosphorylated", "are phosphorylated by", "phosphorylated by atm", "atm cortez", "cortez et al.", "et al. 1999", "1999 gatei", "2000 kim", "kim et al.", "et al. 2006", "2006 jowsey", "jowsey et al.", "which triggers recruitment", "triggers recruitment and", "recruitment and activation", "and activation of", "activation of chek2", "chek2 chk2", "chk2 cds1", "et al. 2002", "2002 wilson", "wilson and stern", "and stern 2008", "2008 melchionna", "melchionna et al.", "al. 2000 .

depending", "2000 .

depending on", ".

depending on the", "on the cell", "the cell cycle", "cell cycle stage", "stage brca1", "brca1 and tp53bp1", "and tp53bp1 competitively", "tp53bp1 competitively promote", "competitively promote either", "promote either homology", "either homology directed", "homology directed repair", "repair hdr", "hdr or", "or nonhomologous end", "nonhomologous end joining", "joining nhej", "nhej of", "of dna dsbs.", "dna dsbs. hdr", "dsbs. hdr through", "hdr through homologous", "through homologous recombination", "homologous recombination repair", "repair hrr", "hrr or", "or single strand", "single strand annealing", "annealing ssa", "ssa is", "is promoted by", "promoted by brca1", "by brca1 in", "brca1 in association", "in association with", "association with rbbp8", "rbbp8 ctip", "while nhej is", "nhej is promoted", "promoted by tp53bp1", "by tp53bp1 in", "tp53bp1 in association", "association with rif1", "rif1 escribano", "escribano diaz et", "diaz et al.", "et al. 2013", "al. 2013 .", "activated atm phosphorylates a", "atm phosphorylates a number", "phosphorylates a number of", "a number of proteins", "number of proteins involved", "of proteins involved in", "proteins involved in the", "involved in the dna", "in the dna damage", "the dna damage checkpoint", "dna damage checkpoint and", "damage checkpoint and dna", "checkpoint and dna repair", "dna repair thompson", "repair thompson and", "thompson and schild 2002", "schild 2002 ciccia", "2002 ciccia and", "ciccia and elledge 2010", "2010 thereby", "thereby triggering and coordinating", "triggering and coordinating accumulation", "and coordinating accumulation of", "coordinating accumulation of dna", "accumulation of dna dsb", "of dna dsb repair", "dna dsb repair proteins", "dsb repair proteins in", "repair proteins in nuclear", "proteins in nuclear foci", "in nuclear foci known", "nuclear foci known as", "foci known as ionizing", "known as ionizing radiation", "as ionizing radiation induced", "ionizing radiation induced foci", "induced foci irif", "foci irif .", "irif . while irifs", ". while irifs include", "while irifs include chromatin", "irifs include chromatin regions", "include chromatin regions kilobases", "chromatin regions kilobases away", "regions kilobases away from", "kilobases away from the", "away from the actual", "from the actual dsb", "the actual dsb site", "dsb site this", "site this reactome", "this reactome pathway represents", "reactome pathway represents simplified", "pathway represents simplified foci", "represents simplified foci and", "simplified foci and events", "foci and events that", "and events that happen", "events that happen proximal", "that happen proximal to", "happen proximal to the", "proximal to the dna", "to the dna dsb", "the dna dsb ends.", "dna dsb ends. in", "dsb ends. in general", "in general proteins", "general proteins localizing", "proteins localizing to the", "localizing to the nuclear", "to the nuclear foci", "the nuclear foci in", "nuclear foci in response", "foci in response to", "in response to atm", "response to atm signaling", "to atm signaling are", "atm signaling are cooperatively", "signaling are cooperatively retained", "are cooperatively retained at", "cooperatively retained at the", "retained at the dna", "at the dna dsb", "the dna dsb site", "dsb site forming", "site forming a", "forming a positive feedback", "a positive feedback loop", "positive feedback loop and", "feedback loop and amplifying", "loop and amplifying dna", "and amplifying dna damage", "amplifying dna damage response", "damage response soutoglou", "response soutoglou and", "soutoglou and misteli 2008", "and misteli 2008 .

activated", "misteli 2008 .

activated atm", "2008 .

activated atm phosphorylates", ".

activated atm phosphorylates the", "atm phosphorylates the nbn", "the nbn nbs1", "nbs1 subunit of", "subunit of the mrn", "of the mrn complex", "mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn gatei", "gatei et al. 2000", "2000 as", "as well as the", "well as the nucleosome", "as the nucleosome histone", "the nucleosome histone h2afx", "histone h2afx h2ax", "h2ax on serine", "on serine residue s139", "residue s139 producing", "s139 producing gamma", "gamma h2afx gamma", "h2afx gamma h2ax", "gamma h2ax containing", "h2ax containing nucleosomes", "containing nucleosomes rogakou", "nucleosomes rogakou et", "rogakou et al. 1998", "al. 1998 burma", "1998 burma et", "burma et al. 2001", "et al. 2001 .", "al. 2001 . h2afx", "2001 . h2afx is", ". h2afx is phosphorylated", "h2afx is phosphorylated on", "is phosphorylated on tyrosine", "phosphorylated on tyrosine 142", "tyrosine 142 y142", "y142 under basal", "basal conditions xiao", "conditions xiao et", "xiao et al. 2009", "et al. 2009 .", "al. 2009 . after", "2009 . after atm", ". after atm mediated", "after atm mediated phosphorylation", "mediated phosphorylation of h2afx", "phosphorylation of h2afx on", "of h2afx on s139", "on s139 tyrosine", "s139 tyrosine y142", "tyrosine y142 has to", "y142 has to be", "has to be dephosphorylated", "to be dephosphorylated by", "be dephosphorylated by eya", "dephosphorylated by eya family", "by eya family phosphatases", "eya family phosphatases in", "family phosphatases in order", "phosphatases in order for", "in order for the", "order for the dna", "for the dna repair", "the dna repair to", "dna repair to proceed", "repair to proceed and", "to proceed and to", "proceed and to avoid", "and to avoid apoptosis", "to avoid apoptosis induced", "avoid apoptosis induced by", "apoptosis induced by dna", "induced by dna dsbs", "dna dsbs cook", "dsbs cook et", "cook et al. 2009", "al. 2009 . gamma", "2009 . gamma h2afx", ". gamma h2afx recruits", "gamma h2afx recruits mdc1", "h2afx recruits mdc1 to", "recruits mdc1 to dna", "mdc1 to dna dsbs", "dna dsbs stucki", "dsbs stucki et", "stucki et al. 2005", "et al. 2005 .", "al. 2005 . after", "2005 . after atm", ". after atm phosphorylates", "after atm phosphorylates mdc1", "phosphorylates mdc1 liu", "mdc1 liu et", "liu et al. 2012", "2012 the", "mrn complex gamma", "complex gamma h2afx", "h2afx nucleosomes and", "nucleosomes and mdc1", "and mdc1 serve as", "mdc1 serve as a", "serve as a core", "as a core of", "a core of the", "core of the nuclear", "of the nuclear focus", "the nuclear focus and", "nuclear focus and a", "focus and a platform", "and a platform for", "a platform for the", "platform for the recruitment", "for the recruitment of", "the recruitment of other", "recruitment of other proteins", "of other proteins involved", "other proteins involved in", "proteins involved in dna", "involved in dna damage", "in dna damage signaling", "dna damage signaling and", "damage signaling and repair", "and repair lukas", "repair lukas et", "lukas et al. 2004", "al. 2004 soutoglou", "2004 soutoglou and", "and misteli 2008 .

rnf8", "misteli 2008 .

rnf8 ubiquitin", "2008 .

rnf8 ubiquitin ligase", ".

rnf8 ubiquitin ligase binds", "ubiquitin ligase binds phosphorylated", "ligase binds phosphorylated mdc1", "phosphorylated mdc1 kolas", "mdc1 kolas et", "kolas et al. 2007", "al. 2007 and", "and in cooperation", "in cooperation with herc2", "cooperation with herc2 and", "with herc2 and rnf168", "and rnf168 bekker", "rnf168 bekker jensen", "bekker jensen et al.", "jensen et al. 2010", "al. 2010 campbell", "2010 campbell et", "campbell et al. 2012", "2012 ubiquitinates", "ubiquitinates h2afx mailand", "h2afx mailand et", "mailand et al. 2007", "al. 2007 huen", "2007 huen et", "huen et al. 2007", "al. 2007 stewart", "2007 stewart et", "stewart et al. 2009", "al. 2009 doil", "2009 doil et", "doil et al. 2009", "al. 2009 and", "2009 and histone", "and histone demethylases kdm4a", "histone demethylases kdm4a and", "demethylases kdm4a and kdm4b", "and kdm4b mallette", "kdm4b mallette et", "mallette et al. 2012", "et al. 2012 .

ubiquitinated", "al. 2012 .

ubiquitinated gamma", "2012 .

ubiquitinated gamma h2afx", ".

ubiquitinated gamma h2afx recruits", "gamma h2afx recruits uimc1", "recruits uimc1 rap80", "rap80 promoting", "promoting the assembly of", "the assembly of the", "assembly of the brca1", "of the brca1 a", "the brca1 a complex", "brca1 a complex at", "a complex at dna", "complex at dna dsbs.", "at dna dsbs. the", "dna dsbs. the brca1", "dsbs. the brca1 a", "brca1 a complex consists", "a complex consists of", "complex consists of rap80", "of rap80 fam175a", "abraxas brca1:bard1", "brca1:bard1 heterodimer brcc3", "brcc36 bre", "brcc45 and babam1", "and babam1 merit40", "nba1 wang", "wang et al. 2007", "al. 2007 wang", "2007 wang and", "wang and elledge 2007", "and elledge 2007

ubiquitin", "elledge 2007

ubiquitin mediated", "2007

ubiquitin mediated degradation", "

ubiquitin mediated degradation of", "mediated degradation of kdm4a", "degradation of kdm4a and", "of kdm4a and kdm4b", "kdm4a and kdm4b allows", "and kdm4b allows tp53bp1", "allows tp53bp1 53bp1", "53bp1 to associate", "to associate with histone", "associate with histone h4", "with histone h4 dimethylated", "histone h4 dimethylated on", "h4 dimethylated on lysine", "dimethylated on lysine k21", "lysine k21 h4k20me2", "k21 h4k20me2 mark", "h4k20me2 mark by", "mark by whsc1", "by whsc1 at dna", "whsc1 at dna dsb", "at dna dsb sites", "dsb sites pei", "sites pei et", "pei et al. 2011", "et al. 2011 .

once", "al. 2011 .

once recruited", "2011 .

once recruited to", ".

once recruited to dna", "recruited to dna dsbs", "dna dsbs both", "dsbs both brca1:bard1", "both brca1:bard1 heterodimers and", "brca1:bard1 heterodimers and tp53bp1", "heterodimers and tp53bp1 are", "and tp53bp1 are phosphorylated", "tp53bp1 are phosphorylated by", "are phosphorylated by atm", "by atm cortez", "atm cortez et", "cortez et al. 1999", "al. 1999 gatei", "1999 gatei et", "al. 2000 kim", "2000 kim et", "kim et al. 2006", "al. 2006 jowsey", "2006 jowsey et", "jowsey et al. 2007", "2007 which", "which triggers recruitment and", "triggers recruitment and activation", "recruitment and activation of", "and activation of chek2", "of chek2 chk2", "cds1 wang", "wang et al. 2002", "al. 2002 wilson", "2002 wilson and", "wilson and stern 2008", "stern 2008 melchionna", "2008 melchionna et", "melchionna et al. 2000", "et al. 2000 .

depending", "al. 2000 .

depending on", "2000 .

depending on the", ".

depending on the cell", "on the cell cycle", "the cell cycle stage", "cycle stage brca1", "stage brca1 and", "brca1 and tp53bp1 competitively", "and tp53bp1 competitively promote", "tp53bp1 competitively promote either", "competitively promote either homology", "promote either homology directed", "either homology directed repair", "directed repair hdr", "hdr or nonhomologous", "or nonhomologous end joining", "end joining nhej", "nhej of dna", "of dna dsbs. hdr", "dna dsbs. hdr through", "dsbs. hdr through homologous", "hdr through homologous recombination", "through homologous recombination repair", "recombination repair hrr", "hrr or single", "or single strand annealing", "strand annealing ssa", "ssa is promoted", "is promoted by brca1", "promoted by brca1 in", "by brca1 in association", "brca1 in association with", "in association with rbbp8", "with rbbp8 ctip", "ctip while", "while nhej is promoted", "nhej is promoted by", "is promoted by tp53bp1", "promoted by tp53bp1 in", "by tp53bp1 in association", "tp53bp1 in association with", "in association with rif1", "with rif1 escribano", "rif1 escribano diaz", "escribano diaz et al.", "diaz et al. 2013", "et al. 2013 .", "activated atm phosphorylates a number", "atm phosphorylates a number of", "phosphorylates a number of proteins", "a number of proteins involved", "number of proteins involved in", "of proteins involved in the", "proteins involved in the dna", "involved in the dna damage", "in the dna damage checkpoint", "the dna damage checkpoint and", "dna damage checkpoint and dna", "damage checkpoint and dna repair", "and dna repair thompson", "dna repair thompson and", "repair thompson and schild", "and schild 2002 ciccia", "schild 2002 ciccia and", "2002 ciccia and elledge", "elledge 2010 thereby", "2010 thereby triggering", "thereby triggering and coordinating accumulation", "triggering and coordinating accumulation of", "and coordinating accumulation of dna", "coordinating accumulation of dna dsb", "accumulation of dna dsb repair", "of dna dsb repair proteins", "dna dsb repair proteins in", "dsb repair proteins in nuclear", "repair proteins in nuclear foci", "proteins in nuclear foci known", "in nuclear foci known as", "nuclear foci known as ionizing", "foci known as ionizing radiation", "known as ionizing radiation induced", "as ionizing radiation induced foci", "radiation induced foci irif", "induced foci irif .", "foci irif . while", "irif . while irifs include", ". while irifs include chromatin", "while irifs include chromatin regions", "irifs include chromatin regions kilobases", "include chromatin regions kilobases away", "chromatin regions kilobases away from", "regions kilobases away from the", "kilobases away from the actual", "away from the actual dsb", "from the actual dsb site", "actual dsb site this", "dsb site this reactome", "site this reactome pathway", "this reactome pathway represents simplified", "reactome pathway represents simplified foci", "pathway represents simplified foci and", "represents simplified foci and events", "simplified foci and events that", "foci and events that happen", "and events that happen proximal", "events that happen proximal to", "that happen proximal to the", "happen proximal to the dna", "proximal to the dna dsb", "to the dna dsb ends.", "the dna dsb ends. in", "dna dsb ends. in general", "ends. in general proteins", "in general proteins localizing", "general proteins localizing to", "proteins localizing to the nuclear", "localizing to the nuclear foci", "to the nuclear foci in", "the nuclear foci in response", "nuclear foci in response to", "foci in response to atm", "in response to atm signaling", "response to atm signaling are", "to atm signaling are cooperatively", "atm signaling are cooperatively retained", "signaling are cooperatively retained at", "are cooperatively retained at the", "cooperatively retained at the dna", "retained at the dna dsb", "at the dna dsb site", "dna dsb site forming", "dsb site forming a", "site forming a positive", "forming a positive feedback loop", "a positive feedback loop and", "positive feedback loop and amplifying", "feedback loop and amplifying dna", "loop and amplifying dna damage", "and amplifying dna damage response", "dna damage response soutoglou", "damage response soutoglou and", "response soutoglou and misteli", "soutoglou and misteli 2008 .

activated", "and misteli 2008 .

activated atm", "misteli 2008 .

activated atm phosphorylates", "2008 .

activated atm phosphorylates the", ".

activated atm phosphorylates the nbn", "phosphorylates the nbn nbs1", "nbn nbs1 subunit", "nbs1 subunit of the", "subunit of the mrn complex", "the mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn gatei et", "al. 2000 as", "2000 as well", "as well as the nucleosome", "well as the nucleosome histone", "as the nucleosome histone h2afx", "nucleosome histone h2afx h2ax", "h2afx h2ax on", "h2ax on serine residue", "serine residue s139 producing", "residue s139 producing gamma", "s139 producing gamma h2afx", "producing gamma h2afx gamma", "gamma h2afx gamma h2ax", "gamma h2ax containing nucleosomes", "containing nucleosomes rogakou et", "nucleosomes rogakou et al.", "et al. 1998 burma", "al. 1998 burma et", "1998 burma et al.", "burma et al. 2001 .", "et al. 2001 . h2afx", "al. 2001 . h2afx is", "2001 . h2afx is phosphorylated", ". h2afx is phosphorylated on", "h2afx is phosphorylated on tyrosine", "is phosphorylated on tyrosine 142", "on tyrosine 142 y142", "142 y142 under", "y142 under basal conditions", "under basal conditions xiao", "basal conditions xiao et", "conditions xiao et al.", "xiao et al. 2009 .", "et al. 2009 . after", "al. 2009 . after atm", "2009 . after atm mediated", ". after atm mediated phosphorylation", "after atm mediated phosphorylation of", "atm mediated phosphorylation of h2afx", "mediated phosphorylation of h2afx on", "phosphorylation of h2afx on s139", "h2afx on s139 tyrosine", "on s139 tyrosine y142", "s139 tyrosine y142 has", "tyrosine y142 has to be", "y142 has to be dephosphorylated", "has to be dephosphorylated by", "to be dephosphorylated by eya", "be dephosphorylated by eya family", "dephosphorylated by eya family phosphatases", "by eya family phosphatases in", "eya family phosphatases in order", "family phosphatases in order for", "phosphatases in order for the", "in order for the dna", "order for the dna repair", "for the dna repair to", "the dna repair to proceed", "dna repair to proceed and", "repair to proceed and to", "to proceed and to avoid", "proceed and to avoid apoptosis", "and to avoid apoptosis induced", "to avoid apoptosis induced by", "avoid apoptosis induced by dna", "apoptosis induced by dna dsbs", "by dna dsbs cook", "dna dsbs cook et", "dsbs cook et al.", "cook et al. 2009 .", "et al. 2009 . gamma", "al. 2009 . gamma h2afx", "2009 . gamma h2afx recruits", ". gamma h2afx recruits mdc1", "gamma h2afx recruits mdc1 to", "h2afx recruits mdc1 to dna", "recruits mdc1 to dna dsbs", "to dna dsbs stucki", "dna dsbs stucki et", "dsbs stucki et al.", "stucki et al. 2005 .", "et al. 2005 . after", "al. 2005 . after atm", "2005 . after atm phosphorylates", ". after atm phosphorylates mdc1", "atm phosphorylates mdc1 liu", "phosphorylates mdc1 liu et", "mdc1 liu et al.", "al. 2012 the", "2012 the mrn", "the mrn complex gamma", "mrn complex gamma h2afx", "complex gamma h2afx nucleosomes", "gamma h2afx nucleosomes and", "h2afx nucleosomes and mdc1", "nucleosomes and mdc1 serve", "and mdc1 serve as a", "mdc1 serve as a core", "serve as a core of", "as a core of the", "a core of the nuclear", "core of the nuclear focus", "of the nuclear focus and", "the nuclear focus and a", "nuclear focus and a platform", "focus and a platform for", "and a platform for the", "a platform for the recruitment", "platform for the recruitment of", "for the recruitment of other", "the recruitment of other proteins", "recruitment of other proteins involved", "of other proteins involved in", "other proteins involved in dna", "proteins involved in dna damage", "involved in dna damage signaling", "in dna damage signaling and", "dna damage signaling and repair", "signaling and repair lukas", "and repair lukas et", "repair lukas et al.", "et al. 2004 soutoglou", "al. 2004 soutoglou and", "2004 soutoglou and misteli", "soutoglou and misteli 2008 .

rnf8", "and misteli 2008 .

rnf8 ubiquitin", "misteli 2008 .

rnf8 ubiquitin ligase", "2008 .

rnf8 ubiquitin ligase binds", ".

rnf8 ubiquitin ligase binds phosphorylated", "ubiquitin ligase binds phosphorylated mdc1", "binds phosphorylated mdc1 kolas", "phosphorylated mdc1 kolas et", "mdc1 kolas et al.", "et al. 2007 and", "2007 and in", "and in cooperation with", "in cooperation with herc2 and", "cooperation with herc2 and rnf168", "herc2 and rnf168 bekker", "and rnf168 bekker jensen", "rnf168 bekker jensen et", "bekker jensen et al. 2010", "et al. 2010 campbell", "al. 2010 campbell et", "2010 campbell et al.", "al. 2012 ubiquitinates", "2012 ubiquitinates h2afx", "ubiquitinates h2afx mailand et", "h2afx mailand et al.", "et al. 2007 huen", "al. 2007 huen et", "2007 huen et al.", "et al. 2007 stewart", "al. 2007 stewart et", "2007 stewart et al.", "et al. 2009 doil", "al. 2009 doil et", "2009 doil et al.", "et al. 2009 and", "al. 2009 and histone", "2009 and histone demethylases", "and histone demethylases kdm4a and", "histone demethylases kdm4a and kdm4b", "kdm4a and kdm4b mallette", "and kdm4b mallette et", "kdm4b mallette et al.", "mallette et al. 2012 .

ubiquitinated", "et al. 2012 .

ubiquitinated gamma", "al. 2012 .

ubiquitinated gamma h2afx", "2012 .

ubiquitinated gamma h2afx recruits", ".

ubiquitinated gamma h2afx recruits uimc1", "h2afx recruits uimc1 rap80", "rap80 promoting the", "promoting the assembly of the", "the assembly of the brca1", "assembly of the brca1 a", "of the brca1 a complex", "the brca1 a complex at", "brca1 a complex at dna", "a complex at dna dsbs.", "complex at dna dsbs. the", "at dna dsbs. the brca1", "dna dsbs. the brca1 a", "dsbs. the brca1 a complex", "the brca1 a complex consists", "brca1 a complex consists of", "a complex consists of rap80", "consists of rap80 fam175a", "rap80 fam175a abraxas", "abraxas brca1:bard1 heterodimer", "heterodimer brcc3 brcc36", "bre brcc45 and", "babam1 merit40 nba1", "nba1 wang et", "et al. 2007 wang", "al. 2007 wang and", "2007 wang and elledge", "wang and elledge 2007

ubiquitin", "and elledge 2007

ubiquitin mediated", "elledge 2007

ubiquitin mediated degradation", "2007

ubiquitin mediated degradation of", "

ubiquitin mediated degradation of kdm4a", "mediated degradation of kdm4a and", "degradation of kdm4a and kdm4b", "of kdm4a and kdm4b allows", "kdm4a and kdm4b allows tp53bp1", "kdm4b allows tp53bp1 53bp1", "tp53bp1 53bp1 to", "53bp1 to associate with", "to associate with histone h4", "associate with histone h4 dimethylated", "with histone h4 dimethylated on", "histone h4 dimethylated on lysine", "h4 dimethylated on lysine k21", "on lysine k21 h4k20me2", "lysine k21 h4k20me2 mark", "h4k20me2 mark by whsc1", "mark by whsc1 at", "by whsc1 at dna dsb", "whsc1 at dna dsb sites", "dna dsb sites pei", "dsb sites pei et", "sites pei et al.", "pei et al. 2011 .

once", "et al. 2011 .

once recruited", "al. 2011 .

once recruited to", "2011 .

once recruited to dna", ".

once recruited to dna dsbs", "to dna dsbs both", "dna dsbs both brca1:bard1", "dsbs both brca1:bard1 heterodimers", "both brca1:bard1 heterodimers and tp53bp1", "brca1:bard1 heterodimers and tp53bp1 are", "heterodimers and tp53bp1 are phosphorylated", "and tp53bp1 are phosphorylated by", "tp53bp1 are phosphorylated by atm", "phosphorylated by atm cortez", "by atm cortez et", "atm cortez et al.", "et al. 1999 gatei", "al. 1999 gatei et", "1999 gatei et al.", "et al. 2000 kim", "al. 2000 kim et", "2000 kim et al.", "et al. 2006 jowsey", "al. 2006 jowsey et", "2006 jowsey et al.", "al. 2007 which", "2007 which triggers", "which triggers recruitment and activation", "triggers recruitment and activation of", "recruitment and activation of chek2", "activation of chek2 chk2", "chek2 chk2 cds1", "cds1 wang et", "et al. 2002 wilson", "al. 2002 wilson and", "2002 wilson and stern", "and stern 2008 melchionna", "stern 2008 melchionna et", "2008 melchionna et al.", "melchionna et al. 2000 .

depending", "et al. 2000 .

depending on", "al. 2000 .

depending on the", "2000 .

depending on the cell", ".

depending on the cell cycle", "on the cell cycle stage", "cell cycle stage brca1", "cycle stage brca1 and", "stage brca1 and tp53bp1", "brca1 and tp53bp1 competitively promote", "and tp53bp1 competitively promote either", "tp53bp1 competitively promote either homology", "competitively promote either homology directed", "promote either homology directed repair", "homology directed repair hdr", "repair hdr or", "hdr or nonhomologous end", "nonhomologous end joining nhej", "joining nhej of", "nhej of dna dsbs.", "of dna dsbs. hdr through", "dna dsbs. hdr through homologous", "dsbs. hdr through homologous recombination", "hdr through homologous recombination repair", "homologous recombination repair hrr", "repair hrr or", "hrr or single strand", "single strand annealing ssa", "annealing ssa is", "ssa is promoted by", "is promoted by brca1 in", "promoted by brca1 in association", "by brca1 in association with", "brca1 in association with rbbp8", "association with rbbp8 ctip", "ctip while nhej", "while nhej is promoted by", "nhej is promoted by tp53bp1", "is promoted by tp53bp1 in", "promoted by tp53bp1 in association", "by tp53bp1 in association with", "tp53bp1 in association with rif1", "association with rif1 escribano", "with rif1 escribano diaz", "rif1 escribano diaz et", "escribano diaz et al. 2013", "diaz et al. 2013 ." ] }, { "record_id": "GLY_000594_1_497", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5693568", "r hsa", "hsa 5693568", "r hsa 5693568" ] }, { "record_id": "GLY_000594_1_497", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of d", "d loop", "loop structures", "structures through", "through holliday", "holliday junction", "junction intermediates", "resolution of d", "of d loop", "d loop structures", "loop structures through", "structures through holliday", "through holliday junction", "holliday junction intermediates", "resolution of d loop", "of d loop structures", "d loop structures through", "loop structures through holliday", "structures through holliday junction", "through holliday junction intermediates", "resolution of d loop structures", "of d loop structures through", "d loop structures through holliday", "loop structures through holliday junction", "structures through holliday junction intermediates", "d loops", "loops generated", "generated after", "after strand", "strand invasion", "invasion and", "and dna", "dna repair", "repair synthesis", "synthesis during", "during homologous", "homologous recombination", "recombination repair", "can be", "be resolved", "resolved through", "junction intermediates.

a", "intermediates.

a d", "loop can", "be cleaved", "cleaved by", "by the", "the complex", "complex of", "of mus81", "mus81 and", "and eme1", "or mus81", "and eme2", "and resolved", "resolved without", "without the", "the formation", "formation of", "of double", "double holliday", "holliday junctions", "generating cross", "cross over", "over products.", "products. all", "all steps", "steps involved", "involved in", "in this", "this process", "process have", "have not", "not been", "been elucidated", "osman et", "et al.", "al. 2003", "schwartz et", "al. 2012", "pepe and", "and west", "west 2014", "2014 .

alternatively", "junctions can", "be created", "created by", "by ligation", "ligation of", "of crossed", "crossed strand", "strand intermediates.", "intermediates. double", "can then", "then be", "through the", "the action", "action of", "of the", "the blm", "blm helicase", "helicase complex", "complex known", "known as", "as btrr", "wan et", "al. 2013", "bocquet et", "al. 2014", "2014 .", ". blm", "blm mediated", "mediated resolution", "of holliday", "intermediates prevents", "prevents sister", "sister chromatid", "chromatid exchange", "between mitotic", "mitotic chromosomes", "chromosomes and", "and generates", "generates non", "non crossover", "crossover products.", "products. spidr", "spidr enables", "enables recruitment", "recruitment of", "the bttr", "bttr complex", "complex to", "to the", "the ionizing", "ionizing radiation", "radiation induced", "induced foci.", "foci. the", "of fignl1", "fignl1 and", "and firrm", "through fignl1", "simultaneously interacts", "interacts with", "with spidr", "yuan and", "and chen", "chen 2013", "and rad51", "fernandes et", "al. 2018", "may facilitate", "facilitate the", "the function", "function of", "of spidr", "spidr in", "in promoting", "promoting the", "the no", "no cross", "over route", "route of", "of homologous", "recombination repair.", "repair. mitotic", "mitotic sce", "sce can", "can result", "result in", "in the", "the loss", "loss of", "of heterozygosity", "which can", "can make", "make the", "the cell", "cell homozygous", "homozygous for", "for deleterious", "deleterious recessive", "recessive mutations", "e.g. in", "in tumor", "tumor suppressor", "suppressor genes", "wu and", "and hickson", "hickson 2003", "2003 .", ". double", "can also", "also be", "resolved by", "by cleavage", "mediated by", "by gen1", "gen1 or", "or the", "the slx", "slx mus", "mus complex", "composed of", "of slx1a:slx4", "slx1a:slx4 heterodimer", "heterodimer and", "and a", "a heterodimer", "heterodimer of", "eme1 or", "eme2 .", ". the", "the resolvase", "resolvase activity", "activity of", "of gen1", "gen1 and", "and slx", "mus predominantly", "predominantly results", "results in", "in crossover", "crossover products", "with sce", "fekairi et", "al. 2009", "wyatt et", "sarbajna et", "d loops generated", "loops generated after", "generated after strand", "after strand invasion", "strand invasion and", "invasion and dna", "and dna repair", "dna repair synthesis", "repair synthesis during", "synthesis during homologous", "during homologous recombination", "homologous recombination repair", "repair hrr", "hrr can", "can be resolved", "be resolved through", "resolved through holliday", "holliday junction intermediates.

a", "junction intermediates.

a d", "intermediates.

a d loop", "d loop can", "loop can be", "can be cleaved", "be cleaved by", "cleaved by the", "by the complex", "the complex of", "complex of mus81", "of mus81 and", "mus81 and eme1", "eme1 mus81:eme1", "mus81:eme1 or", "or mus81 and", "mus81 and eme2", "eme2 mus81:eme2", "mus81:eme2 and", "and resolved without", "resolved without the", "without the formation", "the formation of", "formation of double", "of double holliday", "double holliday junctions", "junctions generating", "generating cross over", "cross over products.", "over products. all", "products. all steps", "all steps involved", "steps involved in", "involved in this", "in this process", "this process have", "process have not", "have not been", "not been elucidated", "elucidated osman", "osman et al.", "et al. 2003", "2003 schwartz", "schwartz et al.", "et al. 2012", "2012 pepe", "pepe and west", "and west 2014", "west 2014 .

alternatively", ".

alternatively double", "holliday junctions can", "junctions can be", "can be created", "be created by", "created by ligation", "by ligation of", "ligation of crossed", "of crossed strand", "crossed strand intermediates.", "strand intermediates. double", "intermediates. double holliday", "junctions can then", "can then be", "then be resolved", "resolved through the", "through the action", "the action of", "action of the", "of the blm", "the blm helicase", "blm helicase complex", "helicase complex known", "complex known as", "known as btrr", "btrr blm:top3a:rmi1:rmi2", "wan et al.", "et al. 2013", "2013 bocquet", "bocquet et al.", "et al. 2014", "al. 2014 .", "2014 . blm", ". blm mediated", "blm mediated resolution", "mediated resolution of", "resolution of holliday", "of holliday junction", "junction intermediates prevents", "intermediates prevents sister", "prevents sister chromatid", "sister chromatid exchange", "exchange sce", "sce between", "between mitotic chromosomes", "mitotic chromosomes and", "chromosomes and generates", "and generates non", "generates non crossover", "non crossover products.", "crossover products. spidr", "products. spidr enables", "spidr enables recruitment", "enables recruitment of", "recruitment of the", "of the bttr", "the bttr complex", "bttr complex to", "complex to the", "to the ionizing", "the ionizing radiation", "ionizing radiation induced", "radiation induced foci.", "induced foci. the", "foci. the complex", "complex of fignl1", "of fignl1 and", "fignl1 and firrm", "firrm which", "which through", "fignl1 simultaneously", "simultaneously interacts with", "interacts with spidr", "spidr yuan", "yuan and chen", "and chen 2013", "2013 and", "rad51 yuan", "2013 fernandes", "fernandes et al.", "et al. 2018", "may facilitate the", "facilitate the function", "the function of", "function of spidr", "of spidr in", "spidr in promoting", "in promoting the", "promoting the no", "the no cross", "no cross over", "cross over route", "over route of", "route of homologous", "of homologous recombination", "homologous recombination repair.", "recombination repair. mitotic", "repair. mitotic sce", "mitotic sce can", "sce can result", "can result in", "result in the", "in the loss", "the loss of", "loss of heterozygosity", "heterozygosity loh", "which can make", "can make the", "make the cell", "the cell homozygous", "cell homozygous for", "homozygous for deleterious", "for deleterious recessive", "deleterious recessive mutations", "mutations e.g.", "e.g. in tumor", "in tumor suppressor", "tumor suppressor genes", "wu and hickson", "and hickson 2003", "hickson 2003 .", "2003 . double", ". double holliday", "junctions can also", "can also be", "also be resolved", "be resolved by", "resolved by cleavage", "cleavage mediated", "mediated by gen1", "by gen1 or", "gen1 or the", "or the slx", "the slx mus", "slx mus complex", "complex composed", "composed of slx1a:slx4", "of slx1a:slx4 heterodimer", "slx1a:slx4 heterodimer and", "heterodimer and a", "and a heterodimer", "a heterodimer of", "heterodimer of mus81", "and eme1 or", "or possibly", "possibly eme2", "eme2 . the", ". the resolvase", "the resolvase activity", "resolvase activity of", "activity of gen1", "of gen1 and", "gen1 and slx", "and slx mus", "slx mus predominantly", "mus predominantly results", "predominantly results in", "results in crossover", "in crossover products", "products with", "sce fekairi", "fekairi et al.", "et al. 2009", "2009 wyatt", "wyatt et al.", "2013 sarbajna", "sarbajna et al.", "d loops generated after", "loops generated after strand", "generated after strand invasion", "after strand invasion and", "strand invasion and dna", "invasion and dna repair", "and dna repair synthesis", "dna repair synthesis during", "repair synthesis during homologous", "synthesis during homologous recombination", "during homologous recombination repair", "recombination repair hrr", "hrr can be", "can be resolved through", "be resolved through holliday", "resolved through holliday junction", "through holliday junction intermediates.

a", "holliday junction intermediates.

a d", "junction intermediates.

a d loop", "intermediates.

a d loop can", "d loop can be", "loop can be cleaved", "can be cleaved by", "be cleaved by the", "cleaved by the complex", "by the complex of", "the complex of mus81", "complex of mus81 and", "of mus81 and eme1", "and eme1 mus81:eme1", "mus81:eme1 or mus81", "or mus81 and eme2", "and eme2 mus81:eme2", "mus81:eme2 and resolved", "and resolved without the", "resolved without the formation", "without the formation of", "the formation of double", "formation of double holliday", "of double holliday junctions", "holliday junctions generating", "junctions generating cross", "generating cross over products.", "cross over products. all", "over products. all steps", "products. all steps involved", "all steps involved in", "steps involved in this", "involved in this process", "in this process have", "this process have not", "process have not been", "have not been elucidated", "been elucidated osman", "elucidated osman et", "osman et al. 2003", "al. 2003 schwartz", "2003 schwartz et", "schwartz et al. 2012", "al. 2012 pepe", "2012 pepe and", "pepe and west 2014", "and west 2014 .

alternatively", "2014 .

alternatively double", ".

alternatively double holliday", "double holliday junctions can", "holliday junctions can be", "junctions can be created", "can be created by", "be created by ligation", "created by ligation of", "by ligation of crossed", "ligation of crossed strand", "of crossed strand intermediates.", "crossed strand intermediates. double", "strand intermediates. double holliday", "intermediates. double holliday junctions", "holliday junctions can then", "junctions can then be", "can then be resolved", "then be resolved through", "be resolved through the", "resolved through the action", "through the action of", "the action of the", "action of the blm", "of the blm helicase", "the blm helicase complex", "blm helicase complex known", "helicase complex known as", "complex known as btrr", "as btrr blm:top3a:rmi1:rmi2", "blm:top3a:rmi1:rmi2 wan", "wan et al. 2013", "al. 2013 bocquet", "2013 bocquet et", "bocquet et al. 2014", "et al. 2014 .", "al. 2014 . blm", "2014 . blm mediated", ". blm mediated resolution", "blm mediated resolution of", "mediated resolution of holliday", "resolution of holliday junction", "of holliday junction intermediates", "holliday junction intermediates prevents", "junction intermediates prevents sister", "intermediates prevents sister chromatid", "prevents sister chromatid exchange", "chromatid exchange sce", "sce between mitotic", "between mitotic chromosomes and", "mitotic chromosomes and generates", "chromosomes and generates non", "and generates non crossover", "generates non crossover products.", "non crossover products. spidr", "crossover products. spidr enables", "products. spidr enables recruitment", "spidr enables recruitment of", "enables recruitment of the", "recruitment of the bttr", "of the bttr complex", "the bttr complex to", "bttr complex to the", "complex to the ionizing", "to the ionizing radiation", "the ionizing radiation induced", "ionizing radiation induced foci.", "radiation induced foci. the", "induced foci. the complex", "foci. the complex of", "the complex of fignl1", "complex of fignl1 and", "of fignl1 and firrm", "and firrm which", "which through fignl1", "through fignl1 simultaneously", "fignl1 simultaneously interacts", "simultaneously interacts with spidr", "with spidr yuan", "spidr yuan and", "yuan and chen 2013", "chen 2013 and", "2013 and rad51", "and rad51 yuan", "rad51 yuan and", "chen 2013 fernandes", "2013 fernandes et", "fernandes et al. 2018", "2018 may", "may facilitate the function", "facilitate the function of", "the function of spidr", "function of spidr in", "of spidr in promoting", "spidr in promoting the", "in promoting the no", "promoting the no cross", "the no cross over", "no cross over route", "cross over route of", "over route of homologous", "route of homologous recombination", "of homologous recombination repair.", "homologous recombination repair. mitotic", "recombination repair. mitotic sce", "repair. mitotic sce can", "mitotic sce can result", "sce can result in", "can result in the", "result in the loss", "in the loss of", "the loss of heterozygosity", "of heterozygosity loh", "loh which", "which can make the", "can make the cell", "make the cell homozygous", "the cell homozygous for", "cell homozygous for deleterious", "homozygous for deleterious recessive", "for deleterious recessive mutations", "recessive mutations e.g.", "mutations e.g. in", "e.g. in tumor suppressor", "in tumor suppressor genes", "genes wu", "wu and hickson 2003", "and hickson 2003 .", "hickson 2003 . double", "2003 . double holliday", ". double holliday junctions", "holliday junctions can also", "junctions can also be", "can also be resolved", "also be resolved by", "be resolved by cleavage", "by cleavage mediated", "cleavage mediated by", "mediated by gen1 or", "by gen1 or the", "gen1 or the slx", "or the slx mus", "the slx mus complex", "mus complex composed", "complex composed of", "composed of slx1a:slx4 heterodimer", "of slx1a:slx4 heterodimer and", "slx1a:slx4 heterodimer and a", "heterodimer and a heterodimer", "and a heterodimer of", "a heterodimer of mus81", "heterodimer of mus81 and", "mus81 and eme1 or", "eme1 or possibly", "possibly eme2 .", "eme2 . the resolvase", ". the resolvase activity", "the resolvase activity of", "resolvase activity of gen1", "activity of gen1 and", "of gen1 and slx", "gen1 and slx mus", "and slx mus predominantly", "slx mus predominantly results", "mus predominantly results in", "predominantly results in crossover", "results in crossover products", "crossover products with", "products with sce", "with sce fekairi", "sce fekairi et", "fekairi et al. 2009", "al. 2009 wyatt", "2009 wyatt et", "wyatt et al. 2013", "al. 2013 sarbajna", "2013 sarbajna et", "sarbajna et al. 2014", "d loops generated after strand", "loops generated after strand invasion", "generated after strand invasion and", "after strand invasion and dna", "strand invasion and dna repair", "invasion and dna repair synthesis", "and dna repair synthesis during", "dna repair synthesis during homologous", "repair synthesis during homologous recombination", "synthesis during homologous recombination repair", "homologous recombination repair hrr", "repair hrr can", "hrr can be resolved", "can be resolved through holliday", "be resolved through holliday junction", "resolved through holliday junction intermediates.

a", "through holliday junction intermediates.

a d", "holliday junction intermediates.

a d loop", "junction intermediates.

a d loop can", "intermediates.

a d loop can be", "d loop can be cleaved", "loop can be cleaved by", "can be cleaved by the", "be cleaved by the complex", "cleaved by the complex of", "by the complex of mus81", "the complex of mus81 and", "complex of mus81 and eme1", "mus81 and eme1 mus81:eme1", "eme1 mus81:eme1 or", "mus81:eme1 or mus81 and", "mus81 and eme2 mus81:eme2", "eme2 mus81:eme2 and", "mus81:eme2 and resolved without", "and resolved without the formation", "resolved without the formation of", "without the formation of double", "the formation of double holliday", "formation of double holliday junctions", "double holliday junctions generating", "holliday junctions generating cross", "junctions generating cross over", "generating cross over products. all", "cross over products. all steps", "over products. all steps involved", "products. all steps involved in", "all steps involved in this", "steps involved in this process", "involved in this process have", "in this process have not", "this process have not been", "process have not been elucidated", "not been elucidated osman", "been elucidated osman et", "elucidated osman et al.", "et al. 2003 schwartz", "al. 2003 schwartz et", "2003 schwartz et al.", "et al. 2012 pepe", "al. 2012 pepe and", "2012 pepe and west", "pepe and west 2014 .

alternatively", "west 2014 .

alternatively double", "2014 .

alternatively double holliday", ".

alternatively double holliday junctions", "double holliday junctions can be", "holliday junctions can be created", "junctions can be created by", "can be created by ligation", "be created by ligation of", "created by ligation of crossed", "by ligation of crossed strand", "ligation of crossed strand intermediates.", "of crossed strand intermediates. double", "crossed strand intermediates. double holliday", "strand intermediates. double holliday junctions", "intermediates. double holliday junctions can", "double holliday junctions can then", "holliday junctions can then be", "junctions can then be resolved", "can then be resolved through", "then be resolved through the", "be resolved through the action", "resolved through the action of", "through the action of the", "the action of the blm", "action of the blm helicase", "of the blm helicase complex", "the blm helicase complex known", "blm helicase complex known as", "helicase complex known as btrr", "known as btrr blm:top3a:rmi1:rmi2", "blm:top3a:rmi1:rmi2 wan et", "et al. 2013 bocquet", "al. 2013 bocquet et", "2013 bocquet et al.", "bocquet et al. 2014 .", "et al. 2014 . blm", "al. 2014 . blm mediated", "2014 . blm mediated resolution", ". blm mediated resolution of", "blm mediated resolution of holliday", "mediated resolution of holliday junction", "resolution of holliday junction intermediates", "of holliday junction intermediates prevents", "holliday junction intermediates prevents sister", "junction intermediates prevents sister chromatid", "intermediates prevents sister chromatid exchange", "sister chromatid exchange sce", "exchange sce between", "sce between mitotic chromosomes", "between mitotic chromosomes and generates", "mitotic chromosomes and generates non", "chromosomes and generates non crossover", "and generates non crossover products.", "generates non crossover products. spidr", "non crossover products. spidr enables", "crossover products. spidr enables recruitment", "products. spidr enables recruitment of", "spidr enables recruitment of the", "enables recruitment of the bttr", "recruitment of the bttr complex", "of the bttr complex to", "the bttr complex to the", "bttr complex to the ionizing", "complex to the ionizing radiation", "to the ionizing radiation induced", "the ionizing radiation induced foci.", "ionizing radiation induced foci. the", "radiation induced foci. the complex", "induced foci. the complex of", "foci. the complex of fignl1", "the complex of fignl1 and", "complex of fignl1 and firrm", "fignl1 and firrm which", "firrm which through", "through fignl1 simultaneously interacts", "fignl1 simultaneously interacts with", "interacts with spidr yuan", "with spidr yuan and", "spidr yuan and chen", "and chen 2013 and", "chen 2013 and rad51", "and rad51 yuan and", "rad51 yuan and chen", "and chen 2013 fernandes", "chen 2013 fernandes et", "2013 fernandes et al.", "al. 2018 may", "2018 may facilitate", "may facilitate the function of", "facilitate the function of spidr", "the function of spidr in", "function of spidr in promoting", "of spidr in promoting the", "spidr in promoting the no", "in promoting the no cross", "promoting the no cross over", "the no cross over route", "no cross over route of", "cross over route of homologous", "over route of homologous recombination", "route of homologous recombination repair.", "of homologous recombination repair. mitotic", "homologous recombination repair. mitotic sce", "recombination repair. mitotic sce can", "repair. mitotic sce can result", "mitotic sce can result in", "sce can result in the", "can result in the loss", "result in the loss of", "in the loss of heterozygosity", "loss of heterozygosity loh", "loh which can", "which can make the cell", "can make the cell homozygous", "make the cell homozygous for", "the cell homozygous for deleterious", "cell homozygous for deleterious recessive", "homozygous for deleterious recessive mutations", "deleterious recessive mutations e.g.", "recessive mutations e.g. in", "mutations e.g. in tumor", "e.g. in tumor suppressor genes", "suppressor genes wu", "genes wu and", "wu and hickson 2003 .", "and hickson 2003 . double", "hickson 2003 . double holliday", "2003 . double holliday junctions", ". double holliday junctions can", "double holliday junctions can also", "holliday junctions can also be", "junctions can also be resolved", "can also be resolved by", "also be resolved by cleavage", "resolved by cleavage mediated", "by cleavage mediated by", "cleavage mediated by gen1", "mediated by gen1 or the", "by gen1 or the slx", "gen1 or the slx mus", "or the slx mus complex", "slx mus complex composed", "mus complex composed of", "complex composed of slx1a:slx4", "composed of slx1a:slx4 heterodimer and", "of slx1a:slx4 heterodimer and a", "slx1a:slx4 heterodimer and a heterodimer", "heterodimer and a heterodimer of", "and a heterodimer of mus81", "a heterodimer of mus81 and", "heterodimer of mus81 and eme1", "of mus81 and eme1 or", "and eme1 or possibly", "or possibly eme2", "possibly eme2 . the", "eme2 . the resolvase activity", ". the resolvase activity of", "the resolvase activity of gen1", "resolvase activity of gen1 and", "activity of gen1 and slx", "of gen1 and slx mus", "gen1 and slx mus predominantly", "and slx mus predominantly results", "slx mus predominantly results in", "mus predominantly results in crossover", "predominantly results in crossover products", "in crossover products with", "crossover products with sce", "with sce fekairi et", "sce fekairi et al.", "et al. 2009 wyatt", "al. 2009 wyatt et", "2009 wyatt et al.", "et al. 2013 sarbajna", "al. 2013 sarbajna et", "2013 sarbajna et al.", "sarbajna et al. 2014 ." ] }, { "record_id": "GLY_000594_1_498", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5693579", "r hsa", "hsa 5693579", "r hsa 5693579" ] }, { "record_id": "GLY_000594_1_498", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "homologous dna", "dna pairing", "pairing and", "and strand", "strand exchange", "homologous dna pairing", "dna pairing and", "pairing and strand", "and strand exchange", "homologous dna pairing and", "dna pairing and strand", "pairing and strand exchange", "homologous dna pairing and strand", "dna pairing and strand exchange", "the presynaptic", "presynaptic phase", "phase of", "of homologous", "exchange begins", "begins with", "with the", "the displacement", "displacement of", "of rpa", "rpa from", "from 3'", "3' ssdna", "ssdna overhangs", "overhangs created", "created by", "by extensive", "extensive resection", "resection of", "of dna", "dna double", "double strand", "strand break", "ends. rpa", "rpa is", "is displaced", "displaced by", "by the", "the joint", "joint action", "action of", "of rad51", "rad51 and", "and brca2.", "brca2. brca2", "brca2 nucleates", "nucleates rad51", "rad51 on", "on 3'", "leading to", "to formation", "formation of", "of invasive", "invasive rad51", "rad51 nucleofilaments", "nucleofilaments which", "which are", "are stabilized", "stabilized by", "the bcdx2", "bcdx2 complex", "rad51b:rad51c:rad51d:xrcc2 .", ". stable", "stable synaptic", "synaptic pairing", "pairing between", "between recombining", "recombining dna", "dna molecules", "molecules involves", "involves the", "the invasion", "invasion of", "of the", "the homologous", "homologous sister", "sister chromatid", "chromatid duplex", "duplex dna", "dna by", "the rad51", "rad51 nucleofilament", "nucleofilament and", "and base", "base pairing", "between the", "the invading", "invading ssdna", "ssdna and", "and the", "the complementary", "complementary sister", "chromatid dna", "dna strand", "while the", "the non", "non complementary", "complementary strand", "strand of", "the sister", "dna duplex", "duplex is", "is displaced.", "displaced. this", "this results", "results in", "in the", "the formation", "of a", "a d", "d loop", "loop structure", "sung et", "et al.", "2003 .", ". palb2", "palb2 and", "and rad51ap1", "rad51ap1 synergistically", "synergistically stimulate", "stimulate rad51", "rad51 recombinase", "recombinase activity", "activity and", "and d", "loop formation.", "formation. palb2", "palb2 simultaneously", "simultaneously interacts", "interacts with", "with rad51", "brca2 and", "modesti et", "al. 2007", "wiese et", "buisson et", "al. 2010", "dray et", "2010 .", "palb2 also", "also interacts", "with brca1", "and this", "this interaction", "interaction fine", "fine tunes", "tunes the", "the localization", "localization of", "of brca2", "and rad51", "rad51 at", "at dna", "dna dsbs", "zhang et", "al. 2009", "sy et", "2009 .", ". the", "the cx3", "cx3 complex", "composed of", "of rad51c", "rad51c and", "and xrcc3", "binds d", "loop structures", "structures through", "through interaction", "interaction with", "with palb2", "and may", "may be", "be involved", "involved in", "the resolution", "resolution of", "of holliday", "holliday junctions", "chun et", "al. 2013", "park et", "al. 2014", "2014 .

while", ".

while rad52", "rad52 promotes", "promotes formation", "nucleofilaments in", "in yeast", "human brca2", "brca2 performs", "performs this", "this function", "while human", "human rad52", "rad52 regulates", "regulates single", "single strand", "strand annealing", "reviewed by", "by ciccia", "ciccia and", "and elledge", "elledge 2010", "the presynaptic phase", "presynaptic phase of", "phase of homologous", "of homologous dna", "strand exchange begins", "exchange begins with", "begins with the", "with the displacement", "the displacement of", "displacement of rpa", "of rpa from", "rpa from 3'", "from 3' ssdna", "3' ssdna overhangs", "ssdna overhangs created", "overhangs created by", "created by extensive", "by extensive resection", "extensive resection of", "resection of dna", "of dna double", "dna double strand", "double strand break", "break dsb", "dsb ends.", "ends. rpa is", "rpa is displaced", "is displaced by", "displaced by the", "by the joint", "the joint action", "joint action of", "action of rad51", "of rad51 and", "rad51 and brca2.", "and brca2. brca2", "brca2. brca2 nucleates", "brca2 nucleates rad51", "nucleates rad51 on", "rad51 on 3'", "on 3' ssdna", "overhangs leading", "leading to formation", "to formation of", "formation of invasive", "of invasive rad51", "invasive rad51 nucleofilaments", "rad51 nucleofilaments which", "nucleofilaments which are", "which are stabilized", "are stabilized by", "stabilized by the", "by the bcdx2", "the bcdx2 complex", "complex rad51b:rad51c:rad51d:xrcc2", "rad51b:rad51c:rad51d:xrcc2 . stable", ". stable synaptic", "stable synaptic pairing", "synaptic pairing between", "pairing between recombining", "between recombining dna", "recombining dna molecules", "dna molecules involves", "molecules involves the", "involves the invasion", "the invasion of", "invasion of the", "of the homologous", "the homologous sister", "homologous sister chromatid", "sister chromatid duplex", "chromatid duplex dna", "duplex dna by", "dna by the", "by the rad51", "the rad51 nucleofilament", "rad51 nucleofilament and", "nucleofilament and base", "and base pairing", "base pairing between", "pairing between the", "between the invading", "the invading ssdna", "invading ssdna and", "ssdna and the", "and the complementary", "the complementary sister", "complementary sister chromatid", "sister chromatid dna", "chromatid dna strand", "strand while", "while the non", "the non complementary", "non complementary strand", "complementary strand of", "strand of the", "of the sister", "the sister chromatid", "chromatid dna duplex", "dna duplex is", "duplex is displaced.", "is displaced. this", "displaced. this results", "this results in", "results in the", "in the formation", "the formation of", "formation of a", "of a d", "a d loop", "d loop structure", "structure sung", "sung et al.", "al. 2003", "2003 . palb2", ". palb2 and", "palb2 and rad51ap1", "and rad51ap1 synergistically", "rad51ap1 synergistically stimulate", "synergistically stimulate rad51", "stimulate rad51 recombinase", "rad51 recombinase activity", "recombinase activity and", "activity and d", "and d loop", "d loop formation.", "loop formation. palb2", "formation. palb2 simultaneously", "palb2 simultaneously interacts", "simultaneously interacts with", "interacts with rad51", "rad51 brca2", "brca2 and rad51ap1", "rad51ap1 modesti", "modesti et al.", "et al. 2007", "2007 wiese", "wiese et al.", "2007 buisson", "buisson et al.", "et al. 2010", "2010 dray", "dray et al.", "al. 2010 .", "2010 . palb2", ". palb2 also", "palb2 also interacts", "also interacts with", "interacts with brca1", "brca1 and", "and this interaction", "this interaction fine", "interaction fine tunes", "fine tunes the", "tunes the localization", "the localization of", "localization of brca2", "of brca2 and", "brca2 and rad51", "and rad51 at", "rad51 at dna", "at dna dsbs", "dsbs zhang", "zhang et al.", "et al. 2009", "2009 sy", "sy et al.", "al. 2009 .", "2009 . the", ". the cx3", "the cx3 complex", "complex composed", "composed of rad51c", "of rad51c and", "rad51c and xrcc3", "xrcc3 binds", "binds d loop", "d loop structures", "loop structures through", "structures through interaction", "through interaction with", "interaction with palb2", "with palb2 and", "palb2 and may", "and may be", "may be involved", "be involved in", "involved in the", "in the resolution", "the resolution of", "resolution of holliday", "of holliday junctions", "junctions chun", "chun et al.", "et al. 2013", "2013 park", "park et al.", "et al. 2014", "al. 2014 .

while", "2014 .

while rad52", ".

while rad52 promotes", "rad52 promotes formation", "promotes formation of", "rad51 nucleofilaments in", "nucleofilaments in yeast", "yeast human", "human brca2 performs", "brca2 performs this", "performs this function", "function while", "while human rad52", "human rad52 regulates", "rad52 regulates single", "regulates single strand", "single strand annealing", "annealing ssa", "reviewed by ciccia", "by ciccia and", "ciccia and elledge", "and elledge 2010", "elledge 2010 .", "the presynaptic phase of", "presynaptic phase of homologous", "phase of homologous dna", "of homologous dna pairing", "and strand exchange begins", "strand exchange begins with", "exchange begins with the", "begins with the displacement", "with the displacement of", "the displacement of rpa", "displacement of rpa from", "of rpa from 3'", "rpa from 3' ssdna", "from 3' ssdna overhangs", "3' ssdna overhangs created", "ssdna overhangs created by", "overhangs created by extensive", "created by extensive resection", "by extensive resection of", "extensive resection of dna", "resection of dna double", "of dna double strand", "dna double strand break", "strand break dsb", "dsb ends. rpa", "ends. rpa is displaced", "rpa is displaced by", "is displaced by the", "displaced by the joint", "by the joint action", "the joint action of", "joint action of rad51", "action of rad51 and", "of rad51 and brca2.", "rad51 and brca2. brca2", "and brca2. brca2 nucleates", "brca2. brca2 nucleates rad51", "brca2 nucleates rad51 on", "nucleates rad51 on 3'", "rad51 on 3' ssdna", "on 3' ssdna overhangs", "ssdna overhangs leading", "overhangs leading to", "leading to formation of", "to formation of invasive", "formation of invasive rad51", "of invasive rad51 nucleofilaments", "invasive rad51 nucleofilaments which", "rad51 nucleofilaments which are", "nucleofilaments which are stabilized", "which are stabilized by", "are stabilized by the", "stabilized by the bcdx2", "by the bcdx2 complex", "bcdx2 complex rad51b:rad51c:rad51d:xrcc2", "complex rad51b:rad51c:rad51d:xrcc2 .", "rad51b:rad51c:rad51d:xrcc2 . stable synaptic", ". stable synaptic pairing", "stable synaptic pairing between", "synaptic pairing between recombining", "pairing between recombining dna", "between recombining dna molecules", "recombining dna molecules involves", "dna molecules involves the", "molecules involves the invasion", "involves the invasion of", "the invasion of the", "invasion of the homologous", "of the homologous sister", "the homologous sister chromatid", "homologous sister chromatid duplex", "sister chromatid duplex dna", "chromatid duplex dna by", "duplex dna by the", "dna by the rad51", "by the rad51 nucleofilament", "the rad51 nucleofilament and", "rad51 nucleofilament and base", "nucleofilament and base pairing", "and base pairing between", "base pairing between the", "pairing between the invading", "between the invading ssdna", "the invading ssdna and", "invading ssdna and the", "ssdna and the complementary", "and the complementary sister", "the complementary sister chromatid", "complementary sister chromatid dna", "sister chromatid dna strand", "dna strand while", "strand while the", "while the non complementary", "the non complementary strand", "non complementary strand of", "complementary strand of the", "strand of the sister", "of the sister chromatid", "the sister chromatid dna", "sister chromatid dna duplex", "chromatid dna duplex is", "dna duplex is displaced.", "duplex is displaced. this", "is displaced. this results", "displaced. this results in", "this results in the", "results in the formation", "in the formation of", "the formation of a", "formation of a d", "of a d loop", "a d loop structure", "loop structure sung", "structure sung et", "et al. 2003", "al. 2003 .", "2003 . palb2 and", ". palb2 and rad51ap1", "palb2 and rad51ap1 synergistically", "and rad51ap1 synergistically stimulate", "rad51ap1 synergistically stimulate rad51", "synergistically stimulate rad51 recombinase", "stimulate rad51 recombinase activity", "rad51 recombinase activity and", "recombinase activity and d", "activity and d loop", "and d loop formation.", "d loop formation. palb2", "loop formation. palb2 simultaneously", "formation. palb2 simultaneously interacts", "palb2 simultaneously interacts with", "simultaneously interacts with rad51", "with rad51 brca2", "rad51 brca2 and", "and rad51ap1 modesti", "rad51ap1 modesti et", "modesti et al. 2007", "al. 2007 wiese", "2007 wiese et", "wiese et al. 2007", "al. 2007 buisson", "2007 buisson et", "buisson et al. 2010", "al. 2010 dray", "2010 dray et", "dray et al. 2010", "et al. 2010 .", "al. 2010 . palb2", "2010 . palb2 also", ". palb2 also interacts", "palb2 also interacts with", "also interacts with brca1", "with brca1 and", "brca1 and this", "and this interaction fine", "this interaction fine tunes", "interaction fine tunes the", "fine tunes the localization", "tunes the localization of", "the localization of brca2", "localization of brca2 and", "of brca2 and rad51", "brca2 and rad51 at", "and rad51 at dna", "rad51 at dna dsbs", "dna dsbs zhang", "dsbs zhang et", "zhang et al. 2009", "al. 2009 sy", "2009 sy et", "sy et al. 2009", "et al. 2009 .", "al. 2009 . the", "2009 . the cx3", ". the cx3 complex", "cx3 complex composed", "complex composed of", "composed of rad51c and", "of rad51c and xrcc3", "and xrcc3 binds", "xrcc3 binds d", "binds d loop structures", "d loop structures through", "loop structures through interaction", "structures through interaction with", "through interaction with palb2", "interaction with palb2 and", "with palb2 and may", "palb2 and may be", "and may be involved", "may be involved in", "be involved in the", "involved in the resolution", "in the resolution of", "the resolution of holliday", "resolution of holliday junctions", "holliday junctions chun", "junctions chun et", "chun et al. 2013", "al. 2013 park", "2013 park et", "park et al. 2014", "et al. 2014 .

while", "al. 2014 .

while rad52", "2014 .

while rad52 promotes", ".

while rad52 promotes formation", "rad52 promotes formation of", "promotes formation of invasive", "invasive rad51 nucleofilaments in", "rad51 nucleofilaments in yeast", "in yeast human", "yeast human brca2", "human brca2 performs this", "brca2 performs this function", "this function while", "function while human", "while human rad52 regulates", "human rad52 regulates single", "rad52 regulates single strand", "regulates single strand annealing", "strand annealing ssa", "ssa reviewed", "reviewed by ciccia and", "by ciccia and elledge", "ciccia and elledge 2010", "and elledge 2010 .", "the presynaptic phase of homologous", "presynaptic phase of homologous dna", "phase of homologous dna pairing", "of homologous dna pairing and", "pairing and strand exchange begins", "and strand exchange begins with", "strand exchange begins with the", "exchange begins with the displacement", "begins with the displacement of", "with the displacement of rpa", "the displacement of rpa from", "displacement of rpa from 3'", "of rpa from 3' ssdna", "rpa from 3' ssdna overhangs", "from 3' ssdna overhangs created", "3' ssdna overhangs created by", "ssdna overhangs created by extensive", "overhangs created by extensive resection", "created by extensive resection of", "by extensive resection of dna", "extensive resection of dna double", "resection of dna double strand", "of dna double strand break", "double strand break dsb", "break dsb ends.", "dsb ends. rpa is", "ends. rpa is displaced by", "rpa is displaced by the", "is displaced by the joint", "displaced by the joint action", "by the joint action of", "the joint action of rad51", "joint action of rad51 and", "action of rad51 and brca2.", "of rad51 and brca2. brca2", "rad51 and brca2. brca2 nucleates", "and brca2. brca2 nucleates rad51", "brca2. brca2 nucleates rad51 on", "brca2 nucleates rad51 on 3'", "nucleates rad51 on 3' ssdna", "rad51 on 3' ssdna overhangs", "3' ssdna overhangs leading", "ssdna overhangs leading to", "overhangs leading to formation", "leading to formation of invasive", "to formation of invasive rad51", "formation of invasive rad51 nucleofilaments", "of invasive rad51 nucleofilaments which", "invasive rad51 nucleofilaments which are", "rad51 nucleofilaments which are stabilized", "nucleofilaments which are stabilized by", "which are stabilized by the", "are stabilized by the bcdx2", "stabilized by the bcdx2 complex", "the bcdx2 complex rad51b:rad51c:rad51d:xrcc2", "bcdx2 complex rad51b:rad51c:rad51d:xrcc2 .", "complex rad51b:rad51c:rad51d:xrcc2 . stable", "rad51b:rad51c:rad51d:xrcc2 . stable synaptic pairing", ". stable synaptic pairing between", "stable synaptic pairing between recombining", "synaptic pairing between recombining dna", "pairing between recombining dna molecules", "between recombining dna molecules involves", "recombining dna molecules involves the", "dna molecules involves the invasion", "molecules involves the invasion of", "involves the invasion of the", "the invasion of the homologous", "invasion of the homologous sister", "of the homologous sister chromatid", "the homologous sister chromatid duplex", "homologous sister chromatid duplex dna", "sister chromatid duplex dna by", "chromatid duplex dna by the", "duplex dna by the rad51", "dna by the rad51 nucleofilament", "by the rad51 nucleofilament and", "the rad51 nucleofilament and base", "rad51 nucleofilament and base pairing", "nucleofilament and base pairing between", "and base pairing between the", "base pairing between the invading", "pairing between the invading ssdna", "between the invading ssdna and", "the invading ssdna and the", "invading ssdna and the complementary", "ssdna and the complementary sister", "and the complementary sister chromatid", "the complementary sister chromatid dna", "complementary sister chromatid dna strand", "chromatid dna strand while", "dna strand while the", "strand while the non", "while the non complementary strand", "the non complementary strand of", "non complementary strand of the", "complementary strand of the sister", "strand of the sister chromatid", "of the sister chromatid dna", "the sister chromatid dna duplex", "sister chromatid dna duplex is", "chromatid dna duplex is displaced.", "dna duplex is displaced. this", "duplex is displaced. this results", "is displaced. this results in", "displaced. this results in the", "this results in the formation", "results in the formation of", "in the formation of a", "the formation of a d", "formation of a d loop", "of a d loop structure", "d loop structure sung", "loop structure sung et", "structure sung et al.", "sung et al. 2003", "et al. 2003 .", "al. 2003 . palb2", "2003 . palb2 and rad51ap1", ". palb2 and rad51ap1 synergistically", "palb2 and rad51ap1 synergistically stimulate", "and rad51ap1 synergistically stimulate rad51", "rad51ap1 synergistically stimulate rad51 recombinase", "synergistically stimulate rad51 recombinase activity", "stimulate rad51 recombinase activity and", "rad51 recombinase activity and d", "recombinase activity and d loop", "activity and d loop formation.", "and d loop formation. palb2", "d loop formation. palb2 simultaneously", "loop formation. palb2 simultaneously interacts", "formation. palb2 simultaneously interacts with", "palb2 simultaneously interacts with rad51", "interacts with rad51 brca2", "with rad51 brca2 and", "rad51 brca2 and rad51ap1", "brca2 and rad51ap1 modesti", "and rad51ap1 modesti et", "rad51ap1 modesti et al.", "et al. 2007 wiese", "al. 2007 wiese et", "2007 wiese et al.", "et al. 2007 buisson", "al. 2007 buisson et", "2007 buisson et al.", "et al. 2010 dray", "al. 2010 dray et", "2010 dray et al.", "dray et al. 2010 .", "et al. 2010 . palb2", "al. 2010 . palb2 also", "2010 . palb2 also interacts", ". palb2 also interacts with", "palb2 also interacts with brca1", "interacts with brca1 and", "with brca1 and this", "brca1 and this interaction", "and this interaction fine tunes", "this interaction fine tunes the", "interaction fine tunes the localization", "fine tunes the localization of", "tunes the localization of brca2", "the localization of brca2 and", "localization of brca2 and rad51", "of brca2 and rad51 at", "brca2 and rad51 at dna", "and rad51 at dna dsbs", "at dna dsbs zhang", "dna dsbs zhang et", "dsbs zhang et al.", "et al. 2009 sy", "al. 2009 sy et", "2009 sy et al.", "sy et al. 2009 .", "et al. 2009 . the", "al. 2009 . the cx3", "2009 . the cx3 complex", "the cx3 complex composed", "cx3 complex composed of", "complex composed of rad51c", "composed of rad51c and xrcc3", "rad51c and xrcc3 binds", "and xrcc3 binds d", "xrcc3 binds d loop", "binds d loop structures through", "d loop structures through interaction", "loop structures through interaction with", "structures through interaction with palb2", "through interaction with palb2 and", "interaction with palb2 and may", "with palb2 and may be", "palb2 and may be involved", "and may be involved in", "may be involved in the", "be involved in the resolution", "involved in the resolution of", "in the resolution of holliday", "the resolution of holliday junctions", "of holliday junctions chun", "holliday junctions chun et", "junctions chun et al.", "et al. 2013 park", "al. 2013 park et", "2013 park et al.", "park et al. 2014 .

while", "et al. 2014 .

while rad52", "al. 2014 .

while rad52 promotes", "2014 .

while rad52 promotes formation", ".

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goldberg", "mancias and goldberg 2008", "and goldberg 2008 .", "2008 . soluble cargo", ". soluble cargo in", "soluble cargo in the er", "cargo in the er lumen", "in the er lumen is", "the er lumen is concentrated", "er lumen is concentrated into", "lumen is concentrated into copii", "is concentrated into copii vesicles", "concentrated into copii vesicles through", "into copii vesicles through interaction", "copii vesicles through interaction with", "vesicles through interaction with a", "through interaction with a receptor", "interaction with a receptor of", "with a receptor of the", "a receptor of the ergic", "receptor of the ergic 53", "of the ergic 53 family", "ergic 53 family the", "53 family the p24", "family the p24 family", "the p24 family or the", "p24 family or the erv", "family or the erv family.", "or the erv family. each", "the erv family. each of", "erv family. each of these", "family. each of these families", "each of these families of", "of these families of 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"the copii vesicle along with", "copii vesicle along with the", "vesicle along with the cargo.", "with the cargo. the", "the cargo. the receptors", "cargo. the receptors are", "the receptors are subsequently recycled", "receptors are subsequently recycled to", "are subsequently recycled to the", "subsequently recycled to the er", "recycled to the er in", "to the er in copi", "the er in copi vesicles", "er in copi vesicles through", "in copi vesicles through retrograde", "copi vesicles through retrograde traffic", "through retrograde traffic reviewed", "retrograde traffic reviewed in", "traffic reviewed in dancourt", "reviewed in dancourt and barlowe", "dancourt and barlowe 2010", "and barlowe 2010 .", "2010 . packaging of", ". packaging of large", "packaging of large cargo such", "of large cargo such as", "large cargo such as fibrillar", "cargo such as fibrillar collagen", "such as fibrillar collagen depends", "as fibrillar collagen depends on", "fibrillar collagen depends on the", "collagen depends on the transmembrane", "depends on the transmembrane accessory", "on the transmembrane accessory factors", "the transmembrane accessory factors mia3", "accessory factors mia3 also", "factors mia3 also known", "mia3 also known as", "known as tango1 and", "as tango1 and ctage5.", "and ctage5. like the", "ctage5. like the ergic", "like the ergic p24", "the ergic p24 and", "ergic p24 and erv", "p24 and erv cargo receptors", "erv cargo receptors mia3", "cargo receptors mia3 and", "receptors mia3 and mia2", "mia3 and mia2 also", "and mia2 also known", "mia2 also known as", "known as ctage5 interact", "as ctage5 interact both", "ctage5 interact both with", "interact both with the collagen", "both with the collagen cargo", "with the collagen cargo and", "the collagen cargo and with", "collagen cargo and with components", "cargo and with components of", "components of the copii coat.", "of the copii coat. unlike", "the copii coat. unlike the", "copii coat. unlike the other", "coat. unlike the other cargo", "unlike the other cargo receptors", "other cargo receptors however", "receptors however mia3", "however mia3 and mia2", "mia3 and mia2 are not", "and mia2 are not loaded", "mia2 are not loaded into", "are not loaded into the", "not loaded into the vesicle", "loaded into the vesicle but", "into the vesicle but remain", "the vesicle but remain in", "vesicle but remain in the", "but remain in the er", "remain in the er membrane", "the er membrane reviewed", "er membrane reviewed in", "membrane reviewed in malhotra", "reviewed in malhotra and erlmann", "malhotra and erlmann 2011", "erlmann 2011 malhotra", "2011 malhotra et al", "malhotra et al 2015", "et al 2015 ." ] }, { "record_id": "GLY_000594_1_502", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "606279", "r hsa", "hsa 606279", "r hsa 606279" ] }, { "record_id": "GLY_000594_1_502", "filename": "human_protein_pathways_reactome", "fieldtype": "text", 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an", "generation.

an antiport", "atp adp", "adp translocase", "preferentially exports", "exports atp", "atp from", "matrix thereby", "thereby maintaining", "maintaining a", "a high", "high adp:atp", "adp:atp ratio", "ratio in", "matrix. the", "the tight", "tight coupling", "coupling of", "of electron", "electron flow", "to atp", "atp synthesis", "synthesis means", "means oxygen", "oxygen consumption", "consumption is", "is dependent", "dependent on", "on adp", "adp availability", "termed respiratory", "respiratory control", "control .", ". high", "high adp", "low atp", "increases electron", "flow thereby", "thereby increasing", "increasing oxygen", "consumption and", "and low", "low adp", "high atp", "decreases electron", "flow and", "and thereby", "thereby decreases", "decreases oxygen", "oxygen consumption.", "consumption. there", "there are", "are many", "many inhibitors", "inhibitors of", "of mitochondrial", "mitochondrial atp", "atp synthesis.", "synthesis. most", "most act", "act by", "by either", "either blocking", "blocking the", "the flow", "flow of", "eg cyanide", "carbon monoxide", "or uncoupling", "uncoupling electron", "flow from", "from atp", "eg dinitrophenol", "dinitrophenol .", ". thermogenin", "thermogenin is", "is a", "a natural", "natural protein", "protein found", "found in", "in brown", "brown fat.", "fat. newborn", "newborn babies", "babies have", "have a", "a large", "large amount", "amount of", "of brown", "brown fat", "fat and", "and the", "the heat", "heat generated", "generated by", "by thermogenin", "is an", "an alternative", "alternative to", "and thus", "thus electron", "flow only", "only produces", "produces heat", "and allows", "allows the", "the maintenance", "maintenance of", "of body", "body temperature", "temperature in", "in newborns.

the", "newborns.

the electron", "chain is", "is located", "located in", "inner mitochondrial", "mitochondrial membrane", "membrane and", "and comprises", "comprises some", "some 80", "80 proteins", "proteins organized", "organized in", "in four", "four enzymatic", "enzymatic complexes", "i iv", "iv .", ". complex", "complex v", "v generates", "generates atp", "atp but", "but has", "has no", "no electron", "electron transfer", "transfer activity.", "activity. in", "in addition", "addition to", "to these", "these 5", "5 complexes", "are also", "also two", "two electron", "electron shuttle", "shuttle molecules", "coenzyme q", "also known", "known as", "as ubiquinone", "and cytochrome", "cytochrome c", "cytc .", ". these", "these two", "two molecules", "molecules shuttle", "shuttle electrons", "electrons between", "between the", "the large", "large complexes", "complexes in", "the chain.

how", "chain.

how many", "many atps", "atps are", "are generated", "by this", "this process?", "process? theoretically", "for each", "each glucose", "glucose molecule", "32 atps", "atps can", "can be", "be produced.", "produced. as", "as electrons", "electrons drop", "drop from", "from nadh", "nadh to", "to oxygen", "oxygen in", "the number", "number of", "protons pumped", "pumped out", "out and", "and returning", "returning through", "through atp", "synthase can", "can produce", "produce 2.5", "2.5 atps", "atps per", "per electron", "electron pair.", "each pair", "pair donated", "donated by", "by fadh2", "only 1.5", "1.5 atps", "be formed.", "formed. twelve", "twelve pairs", "pairs of", "electrons are", "are removed", "removed from", "from each", "molecule

10", "

10 by", "by nad+", "nad+ =", "= 25", "25 atps
2", "atps
2 by", "fadh2 =", "= 3", "3 atps.

making", "atps.

making a", "a total", "total of", "of 28", "28 atps.", "atps. however", "2 atps", "are formed", "formed during", "during the", "the krebs'", "krebs' cycle", "cycle and", "and 2", "atps formed", "during glycolysis", "glycolysis for", "molecule therefore", "therefore making", "making a", "total atp", "atp yield", "yield of", "of 32", "32 atps.", "atps. in", "in reality", "the energy", "energy from", "is used", "used for", "for other", "other processes", "such as", "as active", "of important", "important ions", "ions and", "and molecules", "so under", "under conditions", "conditions of", "of normal", "normal respiration", "the actual", "actual atp", "yield probably", "probably does", "does not", "not reach", "reach 32", "32 atps.

the", "atps.

the reducing", "equivalents that", "that fuel", "fuel the", "namely nadh", "and fadh2", "are produced", "produced by", "tca cycle", "the beta", "fatty acids.", "acids. at", "at three", "three steps", "steps in", "isocitrate conversion", "conversion to", "to oxoglutarate", "oxoglutarate conversion", "to succinyl", "succinyl coa", "malate conversion", "to oxaloacetate", "a pair", "pair of", "removed and", "and transferred", "transferred to", "to nad+", "forming nadh", "and h+.", "h+. at", "at a", "a single", "single step", "from succinate", "reducing fad", "fad to", "to fadh2.", "fadh2. from", "one step", "step in", "the process", "process forms", "forms nadh", "and h+", "h+ and", "and another", "another step", "step forms", "forms fadh2.

cytoplasmic", "fadh2.

cytoplasmic nadh", "from glycolysis", "has to", "to be", "be oxidized", "oxidized to", "to reform", "reform nad+", "essential for", "for glycolysis", "otherwise glycolysis", "glycolysis would", "would cease", "cease to", "to function.", "function. there", "there is", "is no", "no carrier", "carrier that", "that transports", "transports nadh", "nadh directly", "directly into", "into the", "matrix and", "membrane is", "is impermeable", "impermeable to", "to nadh", "nadh so", "so the", "the cell", "cell uses", "uses two", "two shuttle", "shuttle systems", "systems to", "to move", "move reducing", "equivalents into", "the mitochondrion", "mitochondrion and", "and regenerate", "regenerate cytosolic", "cytosolic nad+.", "nad+.
the", "
the first", "first is", "the glycerol", "glycerol phosphate", "phosphate shuttle", "which uses", "uses electrons", "electrons from", "from cytosolic", "cytosolic nadh", "to produce", "produce fadh2", "fadh2 within", "within the", "inner membrane.", "membrane. these", "these electrons", "electrons then", "then flow", "to coenzyme", "coenzyme q.", "q. complex", "complex i", "i is", "is bypassed", "bypassed so", "so only", "be formed", "formed per", "per nadh", "nadh via", "via this", "this route.", "route. the", "the overall", "overall balanced", "balanced equation", "summing all", "all the", "the reactions", "reactions in", "in this", "this system", "+ h+", "+ nad+", "= nad+", "+ nadh", "mito.

the", "

the malate", "malate aspartate", "aspartate shuttle", "shuttle uses", "uses the", "of malate", "malate to", "to generate", "generate nadh", "nadh in", "matrix. this", "this nadh", "nadh can", "can then", "then be", "be fed", "fed directly", "directly to", "to complex", "i and", "thus can", "can form", "form 3", "3 atps", "atps via", "via the", "respiratory chain.", "chain. the", "equation is

nadh", "+ fad", "inner memb.", "+ fadh2", "memb.

both", "

both of", "of these", "these shuttle", "systems regenerate", "cytosolic nad+.

the", "nad+.

the entry", "entry point", "point for", "for nadh", "is complex", "nadh dehydrogenase", "the entry", "for fadh2", "q. the", "the input", "input of", "from fatty", "oxidation via", "via ubiquinone", "ubiquinone is", "is complicated", "complicated and", "and not", "not shown", "shown in", "the diagram.", "mitochondria are often", "are often described", "often described as", "described as the", "as the \\powerhouse\\", "the \\powerhouse\\ of", "\\powerhouse\\ of a", "of a cell", "a cell as", "cell as it", "as it is", "it is here", "is here that", "here that energy", "that energy is", "energy is largely", "is largely released", "largely released from", "released from the", "from the oxidation", "the oxidation of", "oxidation of food.", "of food. reducing", "food. reducing equivalents", "reducing equivalents generated", "equivalents generated from", "generated from beta", "from beta oxidation", "beta oxidation of", "oxidation of fatty", "of fatty acids", "fatty acids and", "acids and from", "and from the", "from the krebs", "the krebs cycle", "krebs cycle enter", "cycle enter the", "enter the electron", "the electron transport", "electron transport chain", "chain also", "also called the", "called the respiratory", "the respiratory chain", "respiratory chain .", "chain . during", ". during a", "during a series", "a series of", "series of redox", "of redox reactions", "reactions electrons", "electrons travel down", "travel down the", "down the chain", "the chain releasing", "chain releasing their", "releasing their energy", "their energy in", "energy in controlled", "in controlled steps.", "controlled steps. these", "steps. these reactions", "these reactions drive", "reactions drive the", "drive the active", "the active transport", "active transport of", "transport of protons", "of protons from", "protons from the", "from the mitochondrial", "the mitochondrial matrix", "through the inner", "the inner membrane", "inner membrane to", "membrane to the", "to the intermembrane", "the intermembrane space.", "intermembrane space. the", "space. the respiratory", "respiratory chain consists", "chain consists of", "consists of five", "of five main", "five main types", "main types of", "types of carrier", "carrier flavins", "flavins iron", "iron sulfur centres", "centres quinones", "quinones cytochromes", "cytochromes heme", "proteins and", "and copper. the", "copper. the two", "the two main", "two main reducing", "main reducing equivalents", "reducing equivalents entering", "equivalents entering the", "entering the respiratory", "respiratory chain are", "chain are nadh", "are nadh and", "nadh and fadh2.", "and fadh2. nadh", "fadh2. nadh is", "nadh is linked", "is linked through", "linked through the", "through the nadh", "the nadh specific", "nadh specific dehydrogenase", "specific dehydrogenase whereas", "dehydrogenase whereas fadh2", "whereas fadh2 is", "fadh2 is reoxidised", "is reoxidised within", "reoxidised within succinate", "within succinate dehydrogenase", "succinate dehydrogenase and", "dehydrogenase and a", "and a ubiquinone", "a ubiquinone reductase", "ubiquinone reductase of", "reductase of the", "of the fatty", "the fatty acid", "fatty acid oxidation", "acid oxidation pathway.", "oxidation pathway. oxygen", "pathway. oxygen is", "oxygen is the", "is the final", "the final acceptor", "final acceptor of", "acceptor of electrons", "of electrons and", "electrons and with", "and with protons", "protons is", "is converted to", "converted to form", "to form water", "water the", "the end product", "end product of", "product of aerobic", "of aerobic cellular", "aerobic cellular respiration.", "cellular respiration. a", "respiration. a proton", "a proton electrochemical", "proton electrochemical gradient", "gradient often", "often called protonmotive", "called protonmotive force", "force is", "is established across", "established across the", "across the inner", "membrane with", "with positive charge", "positive charge in", "charge in the", "in the intermembrane", "the intermembrane space", "intermembrane space relative", "space relative to", "relative to the", "to the matrix.", "the matrix. protons", "matrix. protons driven", "protons driven by", "driven by the", "by the proton", "the proton motive", "proton motive force", "can enter atp", "enter atp synthase", "atp synthase thus", "synthase thus returning", "thus returning to", "returning to the", "to the mitochondrial", "the mitochondrial matrix.", "mitochondrial matrix. atp", "matrix. atp synthases", "atp synthases use", "synthases use this", "use this exergonic", "this exergonic flow", "exergonic flow to", "flow to form", "to form atp", "form atp in", "atp in the", "in the matrix", "matrix a", "a process called", "process called chemiosmotic", "called chemiosmotic coupling.", "chemiosmotic coupling. a", "coupling. a by", "a by product", "by product of", "product of this", "of this process", "this process is", "process is heat", "is heat generation.

an", "heat generation.

an antiport", "antiport atp", "atp adp translocase", "translocase preferentially", "preferentially exports atp", "exports atp from", "atp from the", "from the matrix", "the matrix thereby", "matrix thereby maintaining", "thereby maintaining a", "maintaining a high", "a high adp:atp", "high adp:atp ratio", "adp:atp ratio in", "ratio in the", "in the matrix.", "the matrix. the", "matrix. the tight", "the tight coupling", "tight coupling of", "coupling of electron", "of electron flow", "electron flow to", "flow to atp", "to atp synthesis", "atp synthesis means", "synthesis means oxygen", "means oxygen consumption", "oxygen consumption is", "consumption is dependent", "is dependent on", "dependent on adp", "on adp availability", "availability termed", "termed respiratory control", "respiratory control .", "control . high", ". high adp", "adp low", "atp increases", "increases electron flow", "electron flow thereby", "flow thereby increasing", "thereby increasing oxygen", "increasing oxygen consumption", "oxygen consumption and", "consumption and low", "and low adp", "adp high", "atp decreases", "decreases electron flow", "electron flow and", "flow and thereby", "and thereby decreases", "thereby decreases oxygen", "decreases oxygen consumption.", "oxygen consumption. there", "consumption. there are", "there are many", "are many inhibitors", "many inhibitors of", "inhibitors of mitochondrial", "of mitochondrial atp", "mitochondrial atp synthesis.", "atp synthesis. most", "synthesis. most act", "most act by", "act by either", "by either blocking", "either blocking the", "blocking the flow", "the flow of", "flow of electrons", "electrons eg", "cyanide carbon", "monoxide rotenone", "rotenone or", "or uncoupling electron", "uncoupling electron flow", "electron flow from", "flow from atp", "from atp synthesis", "synthesis eg", "eg dinitrophenol .", "dinitrophenol . thermogenin", ". thermogenin is", "thermogenin is a", "is a natural", "a natural protein", "natural protein found", "protein found in", "found in brown", "in brown fat.", "brown fat. newborn", "fat. newborn babies", "newborn babies have", "babies have a", "have a large", "a large amount", "large amount of", "amount of brown", "of brown fat", "brown fat and", "fat and the", "and the heat", "the heat generated", "heat generated by", "generated by thermogenin", "by thermogenin is", "thermogenin is an", "is an alternative", "an alternative to", "alternative to atp", "synthesis and", "and thus electron", "thus electron flow", "electron flow only", "flow only produces", "only produces heat", "heat and", "and allows the", "allows the maintenance", "the maintenance of", "maintenance of body", "of body temperature", "body temperature in", "temperature in newborns.

the", "in newborns.

the electron", "newborns.

the electron transport", "transport chain is", "chain is located", "is located in", "located in the", "in the inner", "the inner mitochondrial", "inner mitochondrial membrane", "mitochondrial membrane and", "membrane and comprises", "and comprises some", "comprises some 80", "some 80 proteins", "80 proteins organized", "proteins organized in", "organized in four", "in four enzymatic", "four enzymatic complexes", "complexes i", "i iv .", "iv . complex", ". complex v", "complex v generates", "v generates atp", "generates atp but", "atp but has", "but has no", "has no electron", "no electron transfer", "electron transfer activity.", "transfer activity. in", "activity. in addition", "in addition to", "addition to these", "to these 5", "these 5 complexes", "complexes there", "are also two", "also two electron", "two electron shuttle", "electron shuttle molecules", "molecules coenzyme", "q also", "also known as", "known as ubiquinone", "ubiquinone coq", "coq and", "and cytochrome c", "c cytc", "cytc . these", ". these two", "these two molecules", "two molecules shuttle", "molecules shuttle electrons", "shuttle electrons between", "electrons between the", "between the large", "the large complexes", "large complexes in", "complexes in the", "in the chain.

how", "the chain.

how many", "chain.

how many atps", "many atps are", "atps are generated", "are generated by", "generated by this", "by this process?", "this process? theoretically", "theoretically for", "for each glucose", "each glucose molecule", "molecule 32", "32 atps can", "atps can be", "can be produced.", "be produced. as", "produced. as electrons", "as electrons drop", "electrons drop from", "drop from nadh", "from nadh to", "nadh to oxygen", "to oxygen in", "oxygen in the", "in the chain", "chain the", "the number of", "number of protons", "of protons pumped", "protons pumped out", "pumped out and", "out and returning", "and returning through", "returning through atp", "through atp synthase", "atp synthase can", "synthase can produce", "can produce 2.5", "produce 2.5 atps", "2.5 atps per", "atps per electron", "per electron pair.", "pair. for", "for each pair", "each pair donated", "pair donated by", "donated by fadh2", "fadh2 only", "only 1.5 atps", "1.5 atps can", "can be formed.", "be formed. twelve", "formed. twelve pairs", "twelve pairs of", "pairs of electrons", "of electrons are", "electrons are removed", "are removed from", "removed from each", "from each glucose", "glucose molecule

10", "molecule

10 by", "

10 by nad+", "by nad+ =", "nad+ = 25", "= 25 atps
2", "25 atps
2 by", "atps
2 by fadh2", "by fadh2 =", "fadh2 = 3", "= 3 atps.

making", "3 atps.

making a", "atps.

making a total", "a total of", "total of 28", "of 28 atps.", "28 atps. however", "however 2", "2 atps are", "atps are formed", "are formed during", "formed during the", "during the krebs'", "the krebs' cycle", "krebs' cycle and", "cycle and 2", "and 2 atps", "2 atps formed", "atps formed during", "formed during glycolysis", "during glycolysis for", "glycolysis for each", "glucose molecule therefore", "molecule therefore making", "therefore making a", "making a total", "a total atp", "total atp yield", "atp yield of", "yield of 32", "of 32 atps.", "32 atps. in", "atps. in reality", "reality the", "the energy from", "energy from the", "from the respiratory", "respiratory chain is", "chain is used", "is used for", "used for other", "for other processes", "processes such", "such as active", "as active transport", "transport of important", "of important ions", "important ions and", "ions and molecules", "molecules so", "so under conditions", "under conditions of", "conditions of normal", "of normal respiration", "respiration the", "the actual atp", "actual atp yield", "atp yield probably", "yield probably does", "probably does not", "does not reach", "not reach 32", "reach 32 atps.

the", "32 atps.

the reducing", "atps.

the reducing equivalents", "reducing equivalents that", "equivalents that fuel", "that fuel the", "fuel the electron", "chain namely", "namely nadh and", "nadh and fadh2", "fadh2 are", "are produced by", "produced by the", "by the krebs", "cycle tca", "and the beta", "the beta oxidation", "of fatty acids.", "fatty acids. at", "acids. at three", "at three steps", "three steps in", "steps in the", "in the krebs", "cycle isocitrate", "isocitrate conversion to", "conversion to oxoglutarate", "oxoglutarate oxoglutarate", "oxoglutarate conversion to", "conversion to succinyl", "to succinyl coa", "coa malate", "malate conversion to", "conversion to oxaloacetate", "a pair of", "pair of electrons", "electrons 2e", "are removed and", "removed and transferred", "and transferred to", "transferred to nad+", "nad+ forming", "forming nadh and", "nadh and h+.", "and h+. at", "h+. at a", "at a single", "a single step", "step a", "removed from succinate", "succinate reducing", "reducing fad to", "fad to fadh2.", "to fadh2. from", "fadh2. from the", "from the beta", "acids one", "one step in", "step in the", "in the process", "the process forms", "process forms nadh", "forms nadh and", "nadh and h+", "and h+ and", "h+ and another", "and another step", "another step forms", "step forms fadh2.

cytoplasmic", "forms fadh2.

cytoplasmic nadh", "nadh generated", "generated from glycolysis", "glycolysis has", "has to be", "to be oxidized", "be oxidized to", "oxidized to reform", "to reform nad+", "nad+ essential", "essential for glycolysis", "glycolysis otherwise", "otherwise glycolysis would", "glycolysis would cease", "would cease to", "cease to function.", "to function. there", "function. there is", "there is no", "is no carrier", "no carrier that", "carrier that transports", "that transports nadh", "transports nadh directly", "nadh directly into", "directly into the", "into the mitochondrial", "mitochondrial matrix and", "matrix and the", "and the inner", "mitochondrial membrane is", "membrane is impermeable", "is impermeable to", "impermeable to nadh", "to nadh so", "nadh so the", "so the cell", "the cell uses", "cell uses two", "uses two shuttle", "two shuttle systems", "shuttle systems to", "systems to move", "to move reducing", "move reducing equivalents", "reducing equivalents into", "equivalents into the", "into the mitochondrion", "the mitochondrion and", "mitochondrion and regenerate", "and regenerate cytosolic", "regenerate cytosolic nad+.", "cytosolic nad+.
the", "nad+.
the first", "
the first is", "first is the", "is the glycerol", "the glycerol phosphate", "glycerol phosphate shuttle", "shuttle which", "which uses electrons", "uses electrons from", "electrons from cytosolic", "from cytosolic nadh", "cytosolic nadh to", "nadh to produce", "to produce fadh2", "produce fadh2 within", "fadh2 within the", "within the inner", "the inner membrane.", "inner membrane. these", "membrane. these electrons", "these electrons then", "electrons then flow", "then flow to", "flow to coenzyme", "to coenzyme q.", "coenzyme q. complex", "q. complex i", "complex i is", "i is bypassed", "is bypassed so", "bypassed so only", "so only 1.5", "can be formed", "be formed per", "formed per nadh", "per nadh via", "nadh via this", "via this route.", "this route. the", "route. the overall", "the overall balanced", "overall balanced equation", "equation summing", "summing all the", "all the reactions", "the reactions in", "reactions in this", "in this system", "system is

nadh", "is

nadh cytosol", "cytosol +", "h+ cytosol", "nad+ mito.", "mito. =", "nad+ cytosol", "nadh mito.", "mito. +", "h+ mito.", "mito.

the malate", "

the malate aspartate", "malate aspartate shuttle", "aspartate shuttle uses", "shuttle uses the", "uses the oxidation", "oxidation of malate", "of malate to", "malate to generate", "to generate nadh", "generate nadh in", "nadh in the", "in the mitochondrial", "mitochondrial matrix. this", "matrix. this nadh", "this nadh can", "nadh can then", "can then be", "then be fed", "be fed directly", "fed directly to", "directly to complex", "to complex i", "complex i and", "i and thus", "and thus can", "thus can form", "can form 3", "form 3 atps", "3 atps via", "atps via the", "via the respiratory", "the respiratory chain.", "respiratory chain. the", "chain. the overall", "balanced equation is

nadh", "fad inner", "memb. =", "fadh2 inner", "inner memb.

both", "memb.

both of", "

both of these", "of these shuttle", "these shuttle systems", "shuttle systems regenerate", "systems regenerate cytosolic", "regenerate cytosolic nad+.

the", "cytosolic nad+.

the entry", "nad+.

the entry point", "entry point for", "point for nadh", "for nadh is", "nadh is complex", "is complex i", "i nadh", "and the entry", "the entry point", "point for fadh2", "for fadh2 is", "is coenzyme", "coenzyme q. the", "q. the input", "the input of", "input of electrons", "of electrons from", "electrons from fatty", "from fatty acid", "acid oxidation via", "oxidation via ubiquinone", "via ubiquinone is", "ubiquinone is complicated", "is complicated and", "complicated and not", "and not shown", "not shown in", "shown in the", "in the diagram.", "mitochondria are often described", "are often described as", "often described as the", "described as the \\powerhouse\\", "as the \\powerhouse\\ of", "the \\powerhouse\\ of a", "\\powerhouse\\ of a cell", "of a cell as", "a cell as it", "cell as it is", "as it is here", "it is here that", "is here that energy", "here that energy is", "that energy is largely", "energy is largely released", "is largely released from", "largely released from the", "released from the oxidation", "from the oxidation of", "the oxidation of food.", "oxidation of food. reducing", "of food. reducing equivalents", "food. reducing equivalents generated", "reducing equivalents generated from", "equivalents generated from beta", "generated from beta oxidation", "from beta oxidation of", "beta oxidation of fatty", "oxidation of fatty acids", "of fatty acids and", "fatty acids and from", "acids and from the", "and from the krebs", "from the krebs cycle", "the krebs cycle enter", "krebs cycle enter the", "cycle enter the electron", "enter the electron transport", "the electron transport chain", "transport chain also", "chain also called", "also called the respiratory", "called the respiratory chain", "the respiratory chain .", "respiratory chain . during", "chain . during a", ". during a series", "during a series of", "a series of redox", "series of redox reactions", "redox reactions electrons", "reactions electrons travel", "electrons travel down the", "travel down the chain", "down the chain releasing", "the chain releasing their", "chain releasing their energy", "releasing their energy in", "their energy in controlled", "energy in controlled steps.", "in controlled steps. these", "controlled steps. these reactions", "steps. these reactions drive", "these reactions drive the", "reactions drive the active", "drive the active transport", "the active transport of", "active transport of protons", "transport of protons from", "of protons from the", "protons from the mitochondrial", "from the mitochondrial matrix", "matrix through", "through the inner membrane", "the inner membrane to", "inner membrane to the", "membrane to the intermembrane", "to the intermembrane space.", "the intermembrane space. the", "intermembrane space. the respiratory", "space. the respiratory chain", "the respiratory chain consists", "respiratory chain consists of", "chain consists of five", "consists of five main", "of five main types", "five main types of", "main types of carrier", "of carrier flavins", "flavins iron sulfur", "sulfur centres quinones", "cytochromes heme proteins", "heme proteins and", "proteins and copper.", "and copper. the two", "copper. the two main", "the two main reducing", "two main reducing equivalents", "main reducing equivalents entering", "reducing equivalents entering the", "equivalents entering the respiratory", "entering the respiratory chain", "the respiratory chain are", "respiratory chain are nadh", "chain are nadh and", "are nadh and fadh2.", "nadh and fadh2. nadh", "and fadh2. nadh is", "fadh2. nadh is linked", "nadh is linked through", "is linked through the", "linked through the nadh", "through the nadh specific", "the nadh specific dehydrogenase", "nadh specific dehydrogenase whereas", "specific dehydrogenase whereas fadh2", "dehydrogenase whereas fadh2 is", "whereas fadh2 is reoxidised", "fadh2 is reoxidised within", "is reoxidised within succinate", "reoxidised within succinate dehydrogenase", "within succinate dehydrogenase and", "succinate dehydrogenase and a", "dehydrogenase and a ubiquinone", "and a ubiquinone reductase", "a ubiquinone reductase of", "ubiquinone reductase of the", "reductase of the fatty", "of the fatty acid", "the fatty acid oxidation", "fatty acid oxidation pathway.", "acid oxidation pathway. oxygen", "oxidation pathway. oxygen is", "pathway. oxygen is the", "oxygen is the final", "is the final acceptor", "the final acceptor of", "final acceptor of electrons", "acceptor of electrons and", "of electrons and with", "electrons and with protons", "with protons is", "protons is converted", "is converted to form", "converted to form water", "form water the", "water the end", "the end product of", "end product of aerobic", "product of aerobic cellular", "of aerobic cellular respiration.", "aerobic cellular respiration. a", "cellular respiration. a proton", "respiration. a proton electrochemical", "a proton electrochemical gradient", "electrochemical gradient often", "gradient often called", "often called protonmotive force", "protonmotive force is", "force is established", "is established across the", "established across the inner", "across the inner membrane", "inner membrane with", "membrane with positive", "with positive charge in", "positive charge in the", "charge in the intermembrane", "in the intermembrane space", "the intermembrane space relative", "intermembrane space relative to", "space relative to the", "relative to the matrix.", "to the matrix. protons", "the matrix. protons driven", "matrix. protons driven by", "protons driven by the", "driven by the proton", "by the proton motive", "the proton motive force", "force can", "can enter atp synthase", "enter atp synthase thus", "atp synthase thus returning", "synthase thus returning to", "thus returning to the", "returning to the mitochondrial", "to the mitochondrial matrix.", "the mitochondrial matrix. atp", "mitochondrial matrix. atp synthases", "matrix. atp synthases use", "atp synthases use this", "synthases use this exergonic", "use this exergonic flow", "this exergonic flow to", "exergonic flow to form", "flow to form atp", "to form atp in", "form atp in the", "atp in the matrix", "the matrix a", "matrix a process", "a process called chemiosmotic", "process called chemiosmotic coupling.", "called chemiosmotic coupling. a", "chemiosmotic coupling. a by", "coupling. a by product", "a by product of", "by product of this", "product of this process", "of this process is", "this process is heat", "process is heat generation.

an", "is heat generation.

an antiport", "generation.

an antiport atp", "antiport atp adp", "adp translocase preferentially", "translocase preferentially exports", "preferentially exports atp from", "exports atp from the", "atp from the matrix", "from the matrix thereby", "the matrix thereby maintaining", "matrix thereby maintaining a", "thereby maintaining a high", "maintaining a high adp:atp", "a high adp:atp ratio", "high adp:atp ratio in", "adp:atp ratio in the", "ratio in the matrix.", "in the matrix. the", "the matrix. the tight", "matrix. the tight coupling", "the tight coupling of", "tight coupling of electron", "coupling of electron flow", "of electron flow to", "electron flow to atp", "flow to atp synthesis", "to atp synthesis means", "atp synthesis means oxygen", "synthesis means oxygen consumption", "means oxygen consumption is", "oxygen consumption is dependent", "consumption is dependent on", "is dependent on adp", "dependent on adp availability", "adp availability termed", "availability termed respiratory", "termed respiratory control .", "respiratory control . high", "control . high adp", "high adp low", "adp low atp", "low atp increases", "atp increases electron", "increases electron flow thereby", "electron flow thereby increasing", "flow thereby increasing oxygen", "thereby increasing oxygen consumption", "increasing oxygen consumption and", "oxygen consumption and low", "consumption and low adp", "low adp high", "adp high atp", "high atp decreases", "atp decreases electron", "decreases electron flow and", "electron flow and thereby", "flow and thereby decreases", "and thereby decreases oxygen", "thereby decreases oxygen consumption.", "decreases oxygen consumption. there", "oxygen consumption. there are", "consumption. there are many", "there are many inhibitors", "are many inhibitors of", "many inhibitors of mitochondrial", "inhibitors of mitochondrial atp", "of mitochondrial atp synthesis.", "mitochondrial atp synthesis. most", "atp synthesis. most act", "synthesis. most act by", "most act by either", "act by either blocking", "by either blocking the", "either blocking the flow", "blocking the flow of", "the flow of electrons", "of electrons eg", "electrons eg cyanide", "eg cyanide carbon", "cyanide carbon monoxide", "carbon monoxide rotenone", "rotenone or uncoupling", "or uncoupling electron flow", "uncoupling electron flow from", "electron flow from atp", "flow from atp synthesis", "atp synthesis eg", "synthesis eg dinitrophenol", "eg dinitrophenol . thermogenin", "dinitrophenol . thermogenin is", ". thermogenin is a", "thermogenin is a natural", "is a natural protein", "a natural protein found", "natural protein found in", "protein found in brown", "found in brown fat.", "in brown fat. newborn", "brown fat. newborn babies", "fat. newborn babies have", "newborn babies have a", "babies have a large", "have a large amount", "a large amount of", "large amount of brown", "amount of brown fat", "of brown fat and", "brown fat and the", "fat and the heat", "and the heat generated", "the heat generated by", "heat generated by thermogenin", "generated by thermogenin is", "by thermogenin is an", "thermogenin is an alternative", "is an alternative to", "an alternative to atp", "alternative to atp synthesis", "atp synthesis and", "synthesis and thus", "and thus electron flow", "thus electron flow only", "electron flow only produces", "flow only produces heat", "produces heat and", "heat and allows", "and allows the maintenance", "allows the maintenance of", "the maintenance of body", "maintenance of body temperature", "of body temperature in", "body temperature in newborns.

the", "temperature in newborns.

the electron", "in newborns.

the electron transport", "newborns.

the electron transport chain", "electron transport chain is", "transport chain is located", "chain is located in", "is located in the", "located in the inner", "in the inner mitochondrial", "the inner mitochondrial membrane", "inner mitochondrial membrane and", "mitochondrial membrane and comprises", "membrane and comprises some", "and comprises some 80", "comprises some 80 proteins", "some 80 proteins organized", "80 proteins organized in", "proteins organized in four", "organized in four enzymatic", "in four enzymatic complexes", "enzymatic complexes i", "complexes i iv", "i iv . complex", "iv . complex v", ". complex v generates", "complex v generates atp", "v generates atp but", "generates atp but has", "atp but has no", "but has no electron", "has no electron transfer", "no electron transfer activity.", "electron transfer activity. in", "transfer activity. in addition", "activity. in addition to", "in addition to these", "addition to these 5", "to these 5 complexes", "5 complexes there", "there are also", "are also two electron", "also two electron shuttle", "two electron shuttle molecules", "shuttle molecules coenzyme", "molecules coenzyme q", "coenzyme q also", "q also known", "also known as ubiquinone", "as ubiquinone coq", "coq and cytochrome", "cytochrome c cytc", "c cytc .", "cytc . these two", ". these two molecules", "these two molecules shuttle", "two molecules shuttle electrons", "molecules shuttle electrons between", "shuttle electrons between the", "electrons between the large", "between the large complexes", "the large complexes in", "large complexes in the", "complexes in the chain.

how", "in the chain.

how many", "the chain.

how many atps", "chain.

how many atps are", "many atps are generated", "atps are generated by", "are generated by this", "generated by this process?", "by this process? theoretically", "process? theoretically for", "theoretically for each", "for each glucose molecule", "glucose molecule 32", "molecule 32 atps", "32 atps can be", "atps can be produced.", "can be produced. as", "be produced. as electrons", "produced. as electrons drop", "as electrons drop from", "electrons drop from nadh", "drop from nadh to", "from nadh to oxygen", "nadh to oxygen in", "to oxygen in the", "oxygen in the chain", "the chain the", "chain the number", "the number of protons", "number of protons pumped", "of protons pumped out", "protons pumped out and", "pumped out and returning", "out and returning through", "and returning through atp", "returning through atp synthase", "through atp synthase can", "atp synthase can produce", "synthase can produce 2.5", "can produce 2.5 atps", "produce 2.5 atps per", "2.5 atps per electron", "atps per electron pair.", "electron pair. for", "pair. for each", "for each pair donated", "each pair donated by", "pair donated by fadh2", "by fadh2 only", "fadh2 only 1.5", "only 1.5 atps can", "1.5 atps can be", "atps can be formed.", "can be formed. twelve", "be formed. twelve pairs", "formed. twelve pairs of", "twelve pairs of electrons", "pairs of electrons are", "of electrons are removed", "electrons are removed from", "are removed from each", "removed from each glucose", "from each glucose molecule", "each glucose molecule

10", "glucose molecule

10 by", "molecule

10 by nad+", "

10 by nad+ =", "by nad+ = 25", "nad+ = 25 atps
2", "= 25 atps
2 by", "25 atps
2 by fadh2", "atps
2 by fadh2 =", "by fadh2 = 3", "fadh2 = 3 atps.

making", "= 3 atps.

making a", "3 atps.

making a total", "atps.

making a total of", "a total of 28", "total of 28 atps.", "of 28 atps. however", "atps. however 2", "however 2 atps", "2 atps are formed", "atps are formed during", "are formed during the", "formed during the krebs'", "during the krebs' cycle", "the krebs' cycle and", "krebs' cycle and 2", "cycle and 2 atps", "and 2 atps formed", "2 atps formed during", "atps formed during glycolysis", "formed during glycolysis for", "during glycolysis for each", "glycolysis for each glucose", "each glucose molecule therefore", "glucose molecule therefore making", "molecule therefore making a", "therefore making a total", "making a total atp", "a total atp yield", "total atp yield of", "atp yield of 32", "yield of 32 atps.", "of 32 atps. in", "32 atps. in reality", "in reality the", "reality the energy", "the energy from the", "energy from the respiratory", "from the respiratory chain", "the respiratory chain is", "respiratory chain is used", "chain is used for", "is used for other", "used for other processes", "other processes such", "processes such as", "such as active transport", "as active transport of", "active transport of important", "transport of important ions", "of important ions and", "important ions and molecules", "and molecules so", "molecules so under", "so under conditions of", "under conditions of normal", "conditions of normal respiration", "normal respiration the", "respiration the actual", "the actual atp yield", "actual atp yield probably", "atp yield probably does", "yield probably does not", "probably does not reach", "does not reach 32", "not reach 32 atps.

the", "reach 32 atps.

the reducing", "32 atps.

the reducing equivalents", "atps.

the reducing equivalents that", "reducing equivalents that fuel", "equivalents that fuel the", "that fuel the electron", "fuel the electron transport", "transport chain namely", "chain namely nadh", "namely nadh and fadh2", "and fadh2 are", "fadh2 are produced", "are produced by the", "produced by the krebs", "by the krebs cycle", "krebs cycle tca", "cycle tca cycle", "tca cycle and", "cycle and the", "and the beta oxidation", "the beta oxidation of", "oxidation of fatty acids.", "of fatty acids. at", "fatty acids. at three", "acids. at three steps", "at three steps in", "three steps in the", "steps in the krebs", "in the krebs cycle", "krebs cycle isocitrate", "cycle isocitrate conversion", "isocitrate conversion to oxoglutarate", "to oxoglutarate oxoglutarate", "oxoglutarate oxoglutarate conversion", "oxoglutarate conversion to succinyl", "conversion to succinyl coa", "succinyl coa malate", "coa malate conversion", "malate conversion to oxaloacetate", "oxaloacetate a", "a pair of electrons", "of electrons 2e", "2e are", "are removed and transferred", "removed and transferred to", "and transferred to nad+", "to nad+ forming", "nad+ forming nadh", "forming nadh and h+.", "nadh and h+. at", "and h+. at a", "h+. at a single", "at a single step", "single step a", "step a pair", "pair of electrons are", "are removed from succinate", "from succinate reducing", "succinate reducing fad", "reducing fad to fadh2.", "fad to fadh2. from", "to fadh2. from the", "fadh2. from the beta", "from the beta oxidation", "fatty acids one", "acids one step", "one step in the", "step in the process", "in the process forms", "the process forms nadh", "process forms nadh and", "forms nadh and h+", "nadh and h+ and", "and h+ and another", "h+ and another step", "and another step forms", "another step forms fadh2.

cytoplasmic", "step forms fadh2.

cytoplasmic nadh", "fadh2.

cytoplasmic nadh generated", "nadh generated from", "from glycolysis has", "glycolysis has to", "has to be oxidized", "to be oxidized to", "be oxidized to reform", "oxidized to reform nad+", "reform nad+ essential", "nad+ essential for", "for glycolysis otherwise", "glycolysis otherwise glycolysis", "otherwise glycolysis would cease", "glycolysis would cease to", "would cease to function.", "cease to function. there", "to function. there is", "function. there is no", "there is no carrier", "is no carrier that", "no carrier that transports", "carrier that transports nadh", "that transports nadh directly", "transports nadh directly into", "nadh directly into the", "directly into the mitochondrial", "into the mitochondrial matrix", "the mitochondrial matrix and", "mitochondrial matrix and the", "matrix and the inner", "and the inner mitochondrial", "inner mitochondrial membrane is", "mitochondrial membrane is impermeable", "membrane is impermeable to", "is impermeable to nadh", "impermeable to nadh so", "to nadh so the", "nadh so the cell", "so the cell uses", "the cell uses two", "cell uses two shuttle", "uses two shuttle systems", "two shuttle systems to", "shuttle systems to move", "systems to move reducing", "to move reducing equivalents", "move reducing equivalents into", "reducing equivalents into the", "equivalents into the mitochondrion", "into the mitochondrion and", "the mitochondrion and regenerate", "mitochondrion and regenerate cytosolic", "and regenerate cytosolic nad+.", "regenerate cytosolic nad+.
the", "cytosolic nad+.
the first", "nad+.
the first is", "
the first is the", "first is the glycerol", "is the glycerol phosphate", "the glycerol phosphate shuttle", "phosphate shuttle which", "shuttle which uses", "which uses electrons from", "uses electrons from cytosolic", "electrons from cytosolic nadh", "from cytosolic nadh to", "cytosolic nadh to produce", "nadh to produce fadh2", "to produce fadh2 within", "produce fadh2 within the", "fadh2 within the inner", "within the inner membrane.", "the inner membrane. these", "inner membrane. these electrons", "membrane. these electrons then", "these electrons then flow", "electrons then flow to", "then flow to coenzyme", "flow to coenzyme q.", "to coenzyme q. complex", "coenzyme q. complex i", "q. complex i is", "complex i is bypassed", "i is bypassed so", "is bypassed so only", "bypassed so only 1.5", "so only 1.5 atps", "atps can be formed", "can be formed per", "be formed per nadh", "formed per nadh via", "per nadh via this", "nadh via this route.", "via this route. the", "this route. the overall", "route. the overall balanced", "the overall balanced equation", "balanced equation summing", "equation summing all", "summing all the reactions", "all the reactions in", "the reactions in this", "reactions in this system", "this system is

nadh", "cytosol + h+", "+ h+ cytosol", "cytosol + nad+", "+ nad+ mito.", "mito. = nad+", "= nad+ cytosol", "cytosol + nadh", "+ nadh mito.", "mito. + h+", "+ h+ mito.", "h+ mito.

the", "mito.

the malate aspartate", "

the malate aspartate shuttle", "malate aspartate shuttle uses", "aspartate shuttle uses the", "shuttle uses the oxidation", "uses the oxidation of", "the oxidation of malate", "oxidation of malate to", "of malate to generate", "malate to generate nadh", "to generate nadh in", "generate nadh in the", "nadh in the mitochondrial", "in the mitochondrial matrix.", "the mitochondrial matrix. this", "mitochondrial matrix. this nadh", "matrix. this nadh can", "this nadh can then", "nadh can then be", "can then be fed", "then be fed directly", "be fed directly to", "fed directly to complex", "directly to complex i", "to complex i and", "complex i and thus", "i and thus can", "and thus can form", "thus can form 3", "can form 3 atps", "form 3 atps via", "3 atps via the", "atps via the respiratory", "via the respiratory chain.", "the respiratory chain. the", "respiratory chain. the overall", "chain. the overall balanced", "overall balanced equation is

nadh", "equation is

nadh cytosol", "cytosol + fad", "+ fad inner", "fad inner memb.", "inner memb. =", "memb. = nad+", "cytosol + fadh2", "+ fadh2 inner", "fadh2 inner memb.", "inner memb.

both of", "memb.

both of these", "

both of these shuttle", "of these shuttle systems", "these shuttle systems regenerate", "shuttle systems regenerate cytosolic", "systems regenerate cytosolic nad+.

the", "regenerate cytosolic nad+.

the entry", "cytosolic nad+.

the entry point", "nad+.

the entry point for", "entry point for nadh", "point for nadh is", "for nadh is complex", "nadh is complex i", "complex i nadh", "i nadh dehydrogenase", "nadh dehydrogenase and", "dehydrogenase and the", "and the entry point", "the entry point for", "entry point for fadh2", "point for fadh2 is", "fadh2 is coenzyme", "is coenzyme q.", "coenzyme q. the input", "q. the input of", "the input of electrons", "input of electrons from", "of electrons from fatty", "electrons from fatty acid", "from fatty acid oxidation", "fatty acid oxidation via", "acid oxidation via ubiquinone", "oxidation via ubiquinone is", "via ubiquinone is complicated", "ubiquinone is complicated and", "is complicated and not", "complicated and not shown", "and not shown in", "not shown in the", "shown in the diagram.", "mitochondria are often described as", "are often described as the", "often described as the \\powerhouse\\", "described as the \\powerhouse\\ of", "as the \\powerhouse\\ of a", "the \\powerhouse\\ of a cell", "\\powerhouse\\ of a cell as", "of a cell as it", "a cell as it is", "cell as it is here", "as it is here that", "it is here that energy", "is here that energy is", "here that energy is largely", "that energy is largely released", "energy is largely released from", "is largely released from the", "largely released from the oxidation", "released from the oxidation of", "from the oxidation of food.", "the oxidation of food. reducing", "oxidation of food. reducing equivalents", "of food. reducing equivalents generated", "food. reducing equivalents generated from", "reducing equivalents generated from beta", "equivalents generated from beta oxidation", "generated from beta oxidation of", "from beta oxidation of fatty", "beta oxidation of fatty acids", "oxidation of fatty acids and", "of fatty acids and from", "fatty acids and from the", "acids and from the krebs", "and from the krebs cycle", "from the krebs cycle enter", "the krebs cycle enter the", "krebs cycle enter the electron", "cycle enter the electron transport", "enter the electron transport chain", "electron transport chain also", "transport chain also called", "chain also called the", "also called the respiratory chain", "called the respiratory chain .", "the respiratory chain . during", "respiratory chain . during a", "chain . during a series", ". during a series of", "during a series of redox", "a series of redox reactions", "of redox reactions electrons", "redox reactions electrons travel", "reactions electrons travel down", "electrons travel down the chain", "travel down the chain releasing", "down the chain releasing their", "the chain releasing their energy", "chain releasing their energy in", "releasing their energy in controlled", "their energy in controlled steps.", "energy in controlled steps. these", "in controlled steps. these reactions", "controlled steps. these reactions drive", "steps. these reactions drive the", "these reactions drive the active", "reactions drive the active transport", "drive the active transport of", "the active transport of protons", "active transport of protons from", "transport of protons from the", "of protons from the mitochondrial", "protons from the mitochondrial matrix", "mitochondrial matrix through", "matrix through the", "through the inner membrane to", "the inner membrane to the", "inner membrane to the intermembrane", "membrane to the intermembrane space.", "to the intermembrane space. the", "the intermembrane space. the respiratory", "intermembrane space. the respiratory chain", "space. the respiratory chain consists", "the respiratory chain consists of", "respiratory chain consists of five", "chain consists of five main", "consists of five main types", "of five main types of", "five main types of carrier", "types of carrier flavins", "carrier flavins iron", "flavins iron sulfur centres", "iron sulfur centres quinones", "centres quinones cytochromes", "quinones cytochromes heme", "heme proteins and copper.", "proteins and copper. the", "and copper. the two main", "copper. the two main reducing", "the two main reducing equivalents", "two main reducing equivalents entering", "main reducing equivalents entering the", "reducing equivalents entering the respiratory", "equivalents entering the respiratory chain", "entering the respiratory chain are", "the respiratory chain are nadh", "respiratory chain are nadh and", "chain are nadh and fadh2.", "are nadh and fadh2. nadh", "nadh and fadh2. nadh is", "and fadh2. nadh is linked", "fadh2. nadh is linked through", "nadh is linked through the", "is linked through the nadh", "linked through the nadh specific", "through the nadh specific dehydrogenase", "the nadh specific dehydrogenase whereas", "nadh specific dehydrogenase whereas fadh2", "specific dehydrogenase whereas fadh2 is", "dehydrogenase whereas fadh2 is reoxidised", "whereas fadh2 is reoxidised within", "fadh2 is reoxidised within succinate", "is reoxidised within succinate dehydrogenase", "reoxidised within succinate dehydrogenase and", "within succinate dehydrogenase and a", "succinate dehydrogenase and a ubiquinone", "dehydrogenase and a ubiquinone reductase", "and a ubiquinone reductase of", "a ubiquinone reductase of the", "ubiquinone reductase of the fatty", "reductase of the fatty acid", "of the fatty acid oxidation", "the fatty acid oxidation pathway.", "fatty acid oxidation pathway. oxygen", "acid oxidation pathway. oxygen is", "oxidation pathway. oxygen is the", "pathway. oxygen is the final", "oxygen is the final acceptor", "is the final acceptor of", "the final acceptor of electrons", "final acceptor of electrons and", "acceptor of electrons and with", "of electrons and with protons", "and with protons is", "with protons is converted", "protons is converted to", "is converted to form water", "to form water the", "form water the end", "water the end product", "the end product of aerobic", "end product of aerobic cellular", "product of aerobic cellular respiration.", "of aerobic cellular respiration. a", "aerobic cellular respiration. a proton", "cellular respiration. a proton electrochemical", "respiration. a proton electrochemical gradient", "proton electrochemical gradient often", "electrochemical gradient often called", "gradient often called protonmotive", "called protonmotive force is", "protonmotive force is established", "force is established across", "is established across the inner", "established across the inner membrane", "the inner membrane with", "inner membrane with positive", "membrane with positive charge", "with positive charge in the", "positive charge in the intermembrane", "charge in the intermembrane space", "in the intermembrane space relative", "the intermembrane space relative to", "intermembrane space relative to the", "space relative to the matrix.", "relative to the matrix. protons", "to the matrix. protons driven", "the matrix. protons driven by", "matrix. protons driven by the", "protons driven by the proton", "driven by the proton motive", "by the proton motive force", "motive force can", "force can enter", "can enter atp synthase thus", "enter atp synthase thus returning", "atp synthase thus returning to", "synthase thus returning to the", "thus returning to the mitochondrial", "returning to the mitochondrial matrix.", "to the mitochondrial matrix. atp", "the mitochondrial matrix. atp synthases", "mitochondrial matrix. atp synthases use", "matrix. atp synthases use this", "atp synthases use this exergonic", "synthases use this exergonic flow", "use this exergonic flow to", "this exergonic flow to form", "exergonic flow to form atp", "flow to form atp in", "to form atp in the", "form atp in the matrix", "in the matrix a", "the matrix a process", "matrix a process called", "a process called chemiosmotic coupling.", "process called chemiosmotic coupling. a", "called chemiosmotic coupling. a by", "chemiosmotic coupling. a by product", "coupling. a by product of", "a by product of this", "by product of this process", "product of this process is", "of this process is heat", "this process is heat generation.

an", "process is heat generation.

an antiport", "heat generation.

an antiport atp", "generation.

an antiport atp adp", "antiport atp adp translocase", "atp adp translocase preferentially", "adp translocase preferentially exports", "translocase preferentially exports atp", "preferentially exports atp from the", "exports atp from the matrix", "atp from the matrix thereby", "from the matrix thereby maintaining", "the matrix thereby maintaining a", "matrix thereby maintaining a high", "thereby maintaining a high adp:atp", "maintaining a high adp:atp ratio", "a high adp:atp ratio in", "high adp:atp ratio in the", "adp:atp ratio in the matrix.", "ratio in the matrix. the", "in the matrix. the tight", "the matrix. the tight coupling", "matrix. the tight coupling of", "the tight coupling of electron", "tight coupling of electron flow", "coupling of electron flow to", "of electron flow to atp", "electron flow to atp synthesis", "flow to atp synthesis means", "to atp synthesis means oxygen", "atp synthesis means oxygen consumption", "synthesis means oxygen consumption is", "means oxygen consumption is dependent", "oxygen consumption is dependent on", "consumption is dependent on adp", "is dependent on adp availability", "on adp availability termed", "adp availability termed respiratory", "availability termed respiratory control", "termed respiratory control . high", "respiratory control . high adp", ". high adp low", "high adp low atp", "low atp increases electron", "atp increases electron flow", "increases electron flow thereby increasing", "electron flow thereby increasing oxygen", "flow thereby increasing oxygen consumption", "thereby increasing oxygen consumption and", "increasing oxygen consumption and low", "oxygen consumption and low adp", "and low adp high", "low adp high atp", "high atp decreases electron", "atp decreases electron flow", "decreases electron flow and thereby", "electron flow and thereby decreases", "flow and thereby decreases oxygen", "and thereby decreases oxygen consumption.", "thereby decreases oxygen consumption. there", "decreases oxygen consumption. there are", "oxygen consumption. there are many", "consumption. there are many inhibitors", "there are many inhibitors of", "are many inhibitors of mitochondrial", "many inhibitors of mitochondrial atp", "inhibitors of mitochondrial atp synthesis.", "of mitochondrial atp synthesis. most", "mitochondrial atp synthesis. most act", "atp synthesis. most act by", "synthesis. most act by either", "most act by either blocking", "act by either blocking the", "by either blocking the flow", "either blocking the flow of", "blocking the flow of electrons", "flow of electrons eg", "of electrons eg cyanide", "eg cyanide carbon monoxide", "monoxide rotenone or", "rotenone or uncoupling electron", "or uncoupling electron flow from", "uncoupling electron flow from atp", "electron flow from atp synthesis", "from atp synthesis eg", "atp synthesis eg dinitrophenol", "synthesis eg dinitrophenol .", "eg dinitrophenol . thermogenin is", "dinitrophenol . thermogenin is a", ". thermogenin is a natural", "thermogenin is a natural protein", "is a natural protein found", "a natural protein found in", "natural protein found in brown", "protein found in brown fat.", "found in brown fat. newborn", "in brown fat. newborn babies", "brown fat. newborn babies have", "fat. newborn babies have a", "newborn babies have a large", "babies have a large amount", "have a large amount of", "a large amount of brown", "large amount of brown fat", "amount of brown fat and", "of brown fat and the", "brown fat and the heat", "fat and the heat generated", "and the heat generated by", "the heat generated by thermogenin", "heat generated by thermogenin is", "generated by thermogenin is an", "by thermogenin is an alternative", "thermogenin is an alternative to", "is an alternative to atp", "an alternative to atp synthesis", "to atp synthesis and", "atp synthesis and thus", "synthesis and thus electron", "and thus electron flow only", "thus electron flow only produces", "electron flow only produces heat", "only produces heat and", "produces heat and allows", "heat and allows the", "and allows the maintenance of", "allows the maintenance of body", "the maintenance of body temperature", "maintenance of body temperature in", "of body temperature in newborns.

the", "body temperature in newborns.

the electron", "temperature in newborns.

the electron transport", "in newborns.

the electron transport chain", "newborns.

the electron transport chain is", "electron transport chain is located", "transport chain is located in", "chain is located in the", "is located in the inner", "located in the inner mitochondrial", "in the inner mitochondrial membrane", "the inner mitochondrial membrane and", "inner mitochondrial membrane and comprises", "mitochondrial membrane and comprises some", "membrane and comprises some 80", "and comprises some 80 proteins", "comprises some 80 proteins organized", "some 80 proteins organized in", "80 proteins organized in four", "proteins organized in four enzymatic", "organized in four enzymatic complexes", "four enzymatic complexes i", "enzymatic complexes i iv", "complexes i iv .", "i iv . complex v", "iv . complex v generates", ". complex v generates atp", "complex v generates atp but", "v generates atp but has", "generates atp but has no", "atp but has no electron", "but has no electron transfer", "has no electron transfer activity.", "no electron transfer activity. in", "electron transfer activity. in addition", "transfer activity. in addition to", "activity. in addition to these", "in addition to these 5", "addition to these 5 complexes", "these 5 complexes there", "complexes there are", "there are also two", "are also two electron shuttle", "also two electron shuttle molecules", "electron shuttle molecules coenzyme", "shuttle molecules coenzyme q", "coenzyme q also known", "q also known as", "known as ubiquinone coq", "ubiquinone coq and", "coq and cytochrome c", "and cytochrome c cytc", "cytochrome c cytc .", "c cytc . these", "cytc . these two molecules", ". these two molecules shuttle", "these two molecules shuttle electrons", "two molecules shuttle electrons between", "molecules shuttle electrons between the", "shuttle electrons between the large", "electrons between the large complexes", "between the large complexes in", "the large complexes in the", "large complexes in the chain.

how", "complexes in the chain.

how many", "in the chain.

how many atps", "the chain.

how many atps are", "chain.

how many atps are generated", "many atps are generated by", "atps are generated by this", "are generated by this process?", "generated by this process? theoretically", "this process? theoretically for", "process? theoretically for each", "theoretically for each glucose", "each glucose molecule 32", "glucose molecule 32 atps", "molecule 32 atps can", "32 atps can be produced.", "atps can be produced. as", "can be produced. as electrons", "be produced. as electrons drop", "produced. as electrons drop from", "as electrons drop from nadh", "electrons drop from nadh to", "drop from nadh to oxygen", "from nadh to oxygen in", "nadh to oxygen in the", "to oxygen in the chain", "in the chain the", "the chain the number", "chain the number of", "the number of protons pumped", "number of protons pumped out", "of protons pumped out and", "protons pumped out and returning", "pumped out and returning through", "out and returning through atp", "and returning through atp synthase", "returning through atp synthase can", "through atp synthase can produce", "atp synthase can produce 2.5", "synthase can produce 2.5 atps", "can produce 2.5 atps per", "produce 2.5 atps per electron", "2.5 atps per electron pair.", "per electron pair. for", "electron pair. for each", "pair. for each pair", "for each pair donated by", "each pair donated by fadh2", "donated by fadh2 only", "by fadh2 only 1.5", "fadh2 only 1.5 atps", "only 1.5 atps can be", "1.5 atps can be formed.", "atps can be formed. twelve", "can be formed. twelve pairs", "be formed. twelve pairs of", "formed. twelve pairs of electrons", "twelve pairs of electrons are", "pairs of electrons are removed", "of electrons are removed from", "electrons are removed from each", "are removed from each glucose", "removed from each glucose molecule", "from each glucose molecule

10", "each glucose molecule

10 by", "glucose molecule

10 by nad+", "molecule

10 by nad+ =", "

10 by nad+ = 25", "by nad+ = 25 atps
2", "nad+ = 25 atps
2 by", "= 25 atps
2 by fadh2", "25 atps
2 by fadh2 =", "atps
2 by fadh2 = 3", "by fadh2 = 3 atps.

making", "fadh2 = 3 atps.

making a", "= 3 atps.

making a total", "3 atps.

making a total of", "atps.

making a total of 28", "a total of 28 atps.", "total of 28 atps. however", "28 atps. however 2", "atps. however 2 atps", "however 2 atps are", "2 atps are formed during", "atps are formed during the", "are formed during the krebs'", "formed during the krebs' cycle", "during the krebs' cycle and", "the krebs' cycle and 2", "krebs' cycle and 2 atps", "cycle and 2 atps formed", "and 2 atps formed during", "2 atps formed during glycolysis", "atps formed during glycolysis for", "formed during glycolysis for each", "during glycolysis for each glucose", "glycolysis for each glucose molecule", "for each glucose molecule therefore", "each glucose molecule therefore making", "glucose molecule therefore making a", "molecule therefore making a total", "therefore making a total atp", "making a total atp yield", "a total atp yield of", "total atp yield of 32", "atp yield of 32 atps.", "yield of 32 atps. in", "of 32 atps. in reality", "atps. in reality the", "in reality the energy", "reality the energy from", "the energy from the respiratory", "energy from the respiratory chain", "from the respiratory chain is", "the respiratory chain is used", "respiratory chain is used for", "chain is used for other", "is used for other processes", "for other processes such", "other processes such as", "processes such as active", "such as active transport of", "as active transport of important", "active transport of important ions", "transport of important ions and", "of important ions and molecules", "ions and molecules so", "and molecules so under", "molecules so under conditions", "so under conditions of normal", "under conditions of normal respiration", "of normal respiration the", "normal respiration the actual", "respiration the actual atp", "the actual atp yield probably", "actual atp yield probably does", "atp yield probably does not", "yield probably does not reach", "probably does not reach 32", "does not reach 32 atps.

the", "not reach 32 atps.

the reducing", "reach 32 atps.

the reducing equivalents", "32 atps.

the reducing equivalents that", "atps.

the reducing equivalents that fuel", "reducing equivalents that fuel the", "equivalents that fuel the electron", "that fuel the electron transport", "fuel the electron transport chain", "electron transport chain namely", "transport chain namely nadh", "chain namely nadh and", "nadh and fadh2 are", "and fadh2 are produced", "fadh2 are produced by", "are produced by the krebs", "produced by the krebs cycle", "the krebs cycle tca", "krebs cycle tca cycle", "tca cycle and the", "cycle and the beta", "and the beta oxidation of", "the beta oxidation of fatty", "beta oxidation of fatty acids.", "oxidation of fatty acids. at", "of fatty acids. at three", "fatty acids. at three steps", "acids. at three steps in", "at three steps in the", "three steps in the krebs", "steps in the krebs cycle", "the krebs cycle isocitrate", "krebs cycle isocitrate conversion", "cycle isocitrate conversion to", "conversion to oxoglutarate oxoglutarate", "to oxoglutarate oxoglutarate conversion", "oxoglutarate oxoglutarate conversion to", "oxoglutarate conversion to succinyl coa", "to succinyl coa malate", "succinyl coa malate conversion", "coa malate conversion to", "to oxaloacetate a", "oxaloacetate a pair", "pair of electrons 2e", "2e are removed", "are removed and transferred to", "removed and transferred to nad+", "transferred to nad+ forming", "to nad+ forming nadh", "nad+ forming nadh and", "forming nadh and h+. at", "nadh and h+. at a", "and h+. at a single", "h+. at a single step", "a single step a", "single step a pair", "step a pair of", "a pair of electrons are", "pair of electrons are removed", "electrons are removed from succinate", "removed from succinate reducing", "from succinate reducing fad", "succinate reducing fad to", "reducing fad to fadh2. from", "fad to fadh2. from the", "to fadh2. from the beta", "fadh2. from the beta oxidation", "from the beta oxidation of", "of fatty acids one", "fatty acids one step", "acids one step in", "one step in the process", "step in the process forms", "in the process forms nadh", "the process forms nadh and", "process forms nadh and h+", "forms nadh and h+ and", "nadh and h+ and another", "and h+ and another step", "h+ and another step forms", "and another step forms fadh2.

cytoplasmic", "another step forms fadh2.

cytoplasmic nadh", "forms fadh2.

cytoplasmic nadh generated", "fadh2.

cytoplasmic nadh generated from", "nadh generated from glycolysis", "generated from glycolysis has", "from glycolysis has to", "glycolysis has to be", "has to be oxidized to", "to be oxidized to reform", "be oxidized to reform nad+", "to reform nad+ essential", "reform nad+ essential for", "nad+ essential for glycolysis", "essential for glycolysis otherwise", "for glycolysis otherwise glycolysis", "glycolysis otherwise glycolysis would", "otherwise glycolysis would cease to", "glycolysis would cease to function.", "would cease to function. there", "cease to function. there is", "to function. there is no", "function. there is no carrier", "there is no carrier that", "is no carrier that transports", "no carrier that transports nadh", "carrier that transports nadh directly", "that transports nadh directly into", "transports nadh directly into the", "nadh directly into the mitochondrial", "directly into the mitochondrial matrix", "into the mitochondrial matrix and", "the mitochondrial matrix and the", "mitochondrial matrix and the inner", "matrix and the inner mitochondrial", "and the inner mitochondrial membrane", "the inner mitochondrial membrane is", "inner mitochondrial membrane is impermeable", "mitochondrial membrane is impermeable to", "membrane is impermeable to nadh", "is impermeable to nadh so", "impermeable to nadh so the", "to nadh so the cell", "nadh so the cell uses", "so the cell uses two", "the cell uses two shuttle", "cell uses two shuttle systems", "uses two shuttle systems to", "two shuttle systems to move", "shuttle systems to move reducing", "systems to move reducing equivalents", "to move reducing equivalents into", "move reducing equivalents into the", "reducing equivalents into the mitochondrion", "equivalents into the mitochondrion and", "into the mitochondrion and regenerate", "the mitochondrion and regenerate cytosolic", "mitochondrion and regenerate cytosolic nad+.", "and regenerate cytosolic nad+.
the", "regenerate cytosolic nad+.
the first", "cytosolic nad+.
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nadh", "system is

nadh cytosol", "is

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the", "h+ mito.

the malate", "mito.

the malate aspartate shuttle", "

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nadh", "balanced equation is

nadh cytosol", "+ fad inner memb.", "inner memb. = nad+", "+ fadh2 inner memb.", "fadh2 inner memb.

both", "inner memb.

both of these", "memb.

both of these shuttle", "

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the", "systems regenerate cytosolic nad+.

the entry", "regenerate cytosolic nad+.

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aminocarboxypropyl group", "an aminocarboxypropyl group to", "aminocarboxypropyl group to yield", "group to yield yw", "to yield yw 86", "yw 86 methylation", "86 methylation of", "methylation of yw 86", "of yw 86 to", "yw 86 to yield", "86 to yield yw", "to yield yw 72", "yw 72 methylation", "72 methylation of", "methylation of yw 72", "of yw 72 to", "yw 72 to yield", "72 to yield yw", "to yield yw 58", "yw 58 and", "58 and methoxycarbonylation", "and methoxycarbonylation of yw", "methoxycarbonylation of yw 58", "of yw 58 to", "yw 58 to yield", "58 to yield wybutosine", "yield wybutosine reviewed", "wybutosine reviewed in", "reviewed in young and", "in young and bandarian", "young and bandarian 2013", "bandarian 2013 perche", "2013 perche letuv\u00e9e", "perche letuv\u00e9e et al.", "letuv\u00e9e et al. 2014", "et al. 2014 .", "al. 2014 . wybutosine", "2014 . wybutosine may", ". wybutosine may further", "wybutosine may further be", "may further be modified", "further be modified by", "be modified by hydroxylation", "modified by hydroxylation and", "by hydroxylation and methylation.", "hydroxylation and methylation. wyosine", "and methylation. wyosine derivatives", "methylation. wyosine derivatives at", "wyosine derivatives at position", "derivatives at position 37", "at position 37 of", "position 37 of trnas", "37 of trnas participate", "of trnas participate in", "trnas participate in translational", "participate in translational fidelity", "in translational fidelity by", "translational fidelity by stabilizing", "fidelity by stabilizing codon", "by stabilizing codon anticodon", "stabilizing codon anticodon pairing", "anticodon pairing konevega", "pairing konevega et", "konevega et al. 2004", "al. 2004 and", "2004 and preventing", "preventing frameshifting waas", "frameshifting waas et", "waas et al. 2007", "et al. 2007 .", "derivatives of wyosine are tricyclic", "of wyosine are tricyclic bases", "wyosine are tricyclic bases found", "are tricyclic bases found at", "tricyclic bases found at nucleotide", "bases found at nucleotide 37", "found at nucleotide 37 of", "at nucleotide 37 of trna", "nucleotide 37 of trna phe", "of trna phe in", "trna phe in eukaryotes.", "phe in eukaryotes. the", "in eukaryotes. the pathway of", "eukaryotes. the pathway of wybutosine", "the pathway of wybutosine synthesis", "pathway of wybutosine synthesis begins", "of wybutosine synthesis begins with", "wybutosine synthesis begins with a", "synthesis begins with a templated", "begins with a templated guanosine", "with a templated guanosine residue", "a templated guanosine residue and", "templated guanosine residue and proceeds", "guanosine residue and proceeds through", "residue and proceeds through 6", "and proceeds through 6 steps", "proceeds through 6 steps catalyzed", "through 6 steps catalyzed by", "6 steps catalyzed by 5", "steps catalyzed by 5 enzymes:", "catalyzed by 5 enzymes: n1", "by 5 enzymes: n1 methylation", "5 enzymes: n1 methylation of", "enzymes: n1 methylation of guanosine", "methylation of guanosine condensation", "of guanosine condensation of", "guanosine condensation of 1", "condensation of 1 methylguanosine with", "of 1 methylguanosine with pyruvate", "1 methylguanosine with pyruvate to", "methylguanosine with pyruvate to yield", "with pyruvate to yield 4", "pyruvate to yield 4 demethylwyosine", "yield 4 demethylwyosine addition", "4 demethylwyosine addition of", "demethylwyosine addition of an", "addition of an aminocarboxypropyl group", "of an aminocarboxypropyl group to", "an aminocarboxypropyl group to yield", "aminocarboxypropyl group to yield yw", "group to yield yw 86", "yield yw 86 methylation", "yw 86 methylation of", "86 methylation of yw", "methylation of yw 86 to", "of yw 86 to yield", "yw 86 to yield yw", "86 to yield yw 72", "yield yw 72 methylation", "yw 72 methylation of", "72 methylation of yw", "methylation of yw 72 to", "of yw 72 to yield", "yw 72 to yield yw", "72 to yield yw 58", "yield yw 58 and", "yw 58 and methoxycarbonylation", "58 and methoxycarbonylation of", "and methoxycarbonylation of yw 58", "methoxycarbonylation of yw 58 to", "of yw 58 to yield", "yw 58 to yield wybutosine", "to yield wybutosine reviewed", "yield wybutosine reviewed in", "wybutosine reviewed in young", "reviewed in young and bandarian", "in young and bandarian 2013", "and bandarian 2013 perche", "bandarian 2013 perche letuv\u00e9e", "2013 perche letuv\u00e9e et", "perche letuv\u00e9e et al. 2014", "letuv\u00e9e et al. 2014 .", "et al. 2014 . wybutosine", "al. 2014 . wybutosine may", "2014 . wybutosine may further", ". wybutosine may further be", "wybutosine may further be modified", "may further be modified by", "further be modified by hydroxylation", "be modified by hydroxylation and", "modified by hydroxylation and methylation.", "by hydroxylation and methylation. wyosine", "hydroxylation and methylation. wyosine derivatives", "and methylation. wyosine derivatives at", "methylation. wyosine derivatives at position", "wyosine derivatives at position 37", "derivatives at position 37 of", "at position 37 of trnas", "position 37 of trnas participate", "37 of trnas participate in", "of trnas participate in translational", "trnas participate in translational fidelity", "participate in translational fidelity by", "in translational fidelity by stabilizing", "translational fidelity by stabilizing codon", "fidelity by stabilizing codon anticodon", "by stabilizing codon anticodon pairing", "codon anticodon pairing konevega", "anticodon pairing konevega et", "pairing konevega et al.", "et al. 2004 and", "al. 2004 and preventing", "2004 and preventing frameshifting", "and preventing frameshifting waas", "preventing frameshifting waas et", "frameshifting waas et al.", "waas et al. 2007 ." ] }, { "record_id": "GLY_000594_1_507", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6783310", "r hsa", "hsa 6783310", "r hsa 6783310" ] }, { "record_id": "GLY_000594_1_507", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fanconi anemia", "anemia pathway", "fanconi anemia pathway", "is a", "a genetic", "genetic disease", "disease of", "of genome", "genome instability", "instability characterized", "characterized by", "by congenital", "congenital skeletal", "skeletal defects", "aplastic anemia", "susceptibility to", "to leukemias", "and cellular", "cellular sensitivity", "sensitivity to", "to dna", "dna damaging", "damaging agents.", "agents. patients", "patients with", "with fa", "fa have", "have been", "been categorized", "categorized into", "into at", "at least", "least 15", "15 complementation", "complementation groups", "fa a", "o and", "p .", ". these", "these complementation", "groups correspond", "correspond to", "to the", "the genes", "genes fanca", "fanco/rad51c and", "and fancp/slx4.", "fancp/slx4. eight", "eight of", "of these", "these proteins", "and fancm", "together with", "with faap24", "apitd1 and", "and stra13", "form a", "a nuclear", "nuclear complex", "complex termed", "termed the", "the fa", "fa core", "core complex.", "complex. the", "core complex", "complex is", "is an", "an e3", "e3 ubiquitin", "ubiquitin ligase", "ligase that", "that recognizes", "recognizes and", "and is", "is activated", "activated by", "by dna", "dna damage", "damage in", "in the", "the form", "form of", "of interstrand", "interstrand crosslinks", "triggering monoubiquitination", "monoubiquitination of", "of fancd2", "fancd2 and", "and fanci", "which initiates", "initiates repair", "repair of", "of icl", "icl dna.

fancd2", "dna.

fancd2 and", "fanci form", "a complex", "complex and", "and are", "are mutually", "mutually dependent", "dependent on", "on one", "one another", "another for", "for their", "their respective", "respective monoubiquitination.", "monoubiquitination. after", "after dna", "damage and", "and during", "during s", "s phase", "fancd2 localizes", "localizes to", "to discrete", "discrete nuclear", "nuclear foci", "foci that", "that colocalize", "colocalize with", "with proteins", "proteins involved", "involved in", "in homologous", "homologous recombination", "recombination repair", "such as", "as brca1", "brca1 and", "and rad51.", "rad51. the", "fa pathway", "pathway is", "is regulated", "regulated by", "by ubiquitination", "ubiquitination and", "and phosphorylation", "phosphorylation of", "and fanci.", "fanci. atr", "atr dependent", "dependent phosphorylation", "of fanci", "fanci and", "and fancd2", "fancd2 promotes", "promotes monoubiquitination", "stimulating the", "cohn and", "and d'andrea", "d'andrea 2008", "wang 2007", "2007 .", ". the", "the complex", "complex of", "of usp1", "usp1 and", "and wdr48", "is responsible", "responsible for", "for deubiquitination", "deubiquitination of", "and negatively", "negatively regulates", "regulates the", "cohn et", "et al.", "al. 2007", ".

monoubiquitinated", "

monoubiquitinated fancd2", "fancd2 recruits", "recruits dna", "dna nucleases", "including slx4", "and fan1", "which unhook", "unhook the", "the icl", "icl from", "from one", "one of", "of the", "the two", "two covalently", "covalently linked", "linked dna", "dna strands.", "strands. the", "the dna", "dna polymerase", "polymerase nu", "performs translesion", "translesion dna", "dna synthesis", "synthesis using", "using the", "dna strand", "strand with", "with unhooked", "unhooked icl", "icl as", "as a", "a template", "thereby bypassing", "bypassing the", "the unhooked", "unhooked icl.", "icl. the", "icl is", "is subsequently", "subsequently removed", "removed from", "from the", "dna via", "via nucleotide", "nucleotide excision", "excision repair", "ner .", ". incision", "incision of", "the stalled", "stalled replication", "replication fork", "fork during", "during the", "the unhooking", "unhooking step", "step generates", "generates a", "a double", "double strand", "strand break", "dsb .", "the dsb", "dsb is", "is repaired", "repaired via", "via homologous", "and involves", "involves the", "fa genes", "genes brca2", "and brip1", "reviewed by", "by deans", "deans and", "and west", "west 2011", "kottemann and", "and smogorzewska", "smogorzewska 2013", "2013 .", ". homozygous", "homozygous mutations", "mutations in", "in brca2", "palb2 or", "or brip1", "brip1 result", "result in", "in fanconi", "while heterozygous", "heterozygous mutations", "in these", "these genes", "genes predispose", "predispose carriers", "carriers to", "to primarily", "primarily breast", "breast and", "and ovarian", "ovarian cancer.", "cancer. well", "well established", "established functions", "functions of", "of brca2", "palb2 and", "brip1 in", "in dna", "dna repair", "repair are", "are brca1", "brca1 dependent", "but it", "it is", "is not", "not yet", "yet clear", "clear whether", "whether there", "there are", "are additional", "additional roles", "roles for", "for these", "proteins in", "the fanconi", "pathway that", "that do", "do not", "not rely", "rely on", "on brca1", "evans and", "and longo", "longo 2014", "jiang and", "and greenberg", "greenberg 2015", "2015 .", ". heterozygous", "heterozygous brca1", "brca1 mutations", "mutations predispose", "to breast", "ovarian cancer", "cancer with", "with high", "high penetrance.", "penetrance. complete", "complete loss", "loss of", "of brca1", "brca1 function", "function is", "is embryonic", "embryonic lethal.", "lethal. it", "it has", "has only", "only recently", "recently been", "been reported", "reported that", "that a", "a partial", "partial germline", "germline loss", "function via", "via mutations", "mutations that", "that diminish", "diminish protein", "protein binding", "binding ability", "ability of", "the brct", "brct domain", "domain of", "brca1 result", "in a", "a fa", "fa like", "like syndrome.", "syndrome. brca1", "brca1 has", "has therefore", "therefore been", "been designated", "designated as", "as the", "the fancs", "fancs gene", "2015 .

the", ".

the fa", "is involved", "in repairing", "repairing dna", "dna icls", "icls that", "that arise", "arise by", "by exposure", "exposure to", "to endogenous", "endogenous mutagens", "mutagens produced", "produced as", "as by", "by products", "products of", "of normal", "normal cellular", "cellular metabolism", "as aldehyde", "aldehyde containing", "containing compounds.", "compounds. disruption", "disruption of", "the aldehyde", "aldehyde dehydrogenase", "dehydrogenase gene", "gene aldh2", "aldh2 in", "in fancd2", "fancd2 deficient", "deficient mice", "mice leads", "leads to", "to severe", "severe developmental", "developmental defects", "early lethality", "lethality and", "and predisposition", "predisposition to", "to leukemia.", "leukemia. in", "in addition", "addition to", "to this", "the double", "double knockout", "knockout mice", "mice are", "are exceptionally", "exceptionally sensitive", "sensitive to", "to ethanol", "ethanol consumption", "as ethanol", "ethanol metabolism", "metabolism results", "results in", "in accumulated", "accumulated levels", "levels of", "of aldehydes", "langevin et", "al. 2011", "2011 .", "anemia fa", "fa is", "is a genetic", "a genetic disease", "genetic disease of", "disease of genome", "of genome instability", "genome instability characterized", "instability characterized by", "characterized by congenital", "by congenital skeletal", "congenital skeletal defects", "defects aplastic", "anemia susceptibility", "susceptibility to leukemias", "leukemias and", "and cellular sensitivity", "cellular sensitivity to", "sensitivity to dna", "to dna damaging", "dna damaging agents.", "damaging agents. patients", "agents. patients with", "patients with fa", "with fa have", "fa have been", "have been categorized", "been categorized into", "categorized into at", "into at least", "at least 15", "least 15 complementation", "15 complementation groups", "groups fa", "and p", "p . these", ". these complementation", "these complementation groups", "complementation groups correspond", "groups correspond to", "correspond to the", "to the genes", "the genes fanca", "fanca fancb", "fancb fancc", "fancc fancd1/brca2", "fancd1/brca2 fancd2", "fancd2 fance", "fance fancf", "fancf fancg", "fancg fancj/brip1", "fancj/brip1 fancl", "fancl fancm", "fancm fancn/palb2", "fancn/palb2 fanco/rad51c", "fanco/rad51c and fancp/slx4.", "and fancp/slx4. eight", "fancp/slx4. eight of", "eight of these", "of these proteins", "proteins fanca", "fancc fance", "fancg fancl", "fancl and", "fancm together", "together with faap24", "faap24 faap100", "faap100 faap20", "faap20 apitd1", "apitd1 and stra13", "stra13 form", "form a nuclear", "a nuclear complex", "nuclear complex termed", "complex termed the", "termed the fa", "the fa core", "fa core complex.", "core complex. the", "complex. the fa", "fa core complex", "core complex is", "complex is an", "is an e3", "an e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase that", "ligase that recognizes", "that recognizes and", "recognizes and is", "and is activated", "is activated by", "activated by dna", "by dna damage", "dna damage in", "damage in the", "in the form", "the form of", "form of interstrand", "of interstrand crosslinks", "crosslinks icls", "triggering monoubiquitination of", "monoubiquitination of fancd2", "of fancd2 and", "fancd2 and fanci", "fanci which", "which initiates repair", "initiates repair of", "repair of icl", "of icl dna.

fancd2", "icl dna.

fancd2 and", "dna.

fancd2 and fanci", "and fanci form", "fanci form a", "form a complex", "a complex and", "complex and are", "and are mutually", "are mutually dependent", "mutually dependent on", "dependent on one", "on one another", "one another for", "another for their", "for their respective", "their respective monoubiquitination.", "respective monoubiquitination. after", "monoubiquitination. after dna", "after dna damage", "dna damage and", "damage and during", "and during s", "during s phase", "phase fancd2", "fancd2 localizes to", "localizes to discrete", "to discrete nuclear", "discrete nuclear foci", "nuclear foci that", "foci that colocalize", "that colocalize with", "colocalize with proteins", "with proteins involved", "proteins involved in", "involved in homologous", "in homologous recombination", "homologous recombination repair", "repair such", "such as brca1", "as brca1 and", "brca1 and rad51.", "and rad51. the", "rad51. the fa", "the fa pathway", "fa pathway is", "pathway is regulated", "is regulated by", "regulated by ubiquitination", "by ubiquitination and", "ubiquitination and phosphorylation", "and phosphorylation of", "phosphorylation of fancd2", "fancd2 and fanci.", "and fanci. atr", "fanci. atr dependent", "atr dependent phosphorylation", "dependent phosphorylation of", "phosphorylation of fanci", "of fanci and", "fanci and fancd2", "and fancd2 promotes", "fancd2 promotes monoubiquitination", "promotes monoubiquitination of", "fancd2 stimulating", "stimulating the fa", "pathway cohn", "cohn and d'andrea", "and d'andrea 2008", "2008 wang", "wang 2007 .", "2007 . the", ". the complex", "the complex of", "complex of usp1", "of usp1 and", "usp1 and wdr48", "wdr48 uaf1", "uaf1 is", "is responsible for", "responsible for deubiquitination", "for deubiquitination of", "deubiquitination of fancd2", "fancd2 and negatively", "and negatively regulates", "negatively regulates the", "regulates the fa", "cohn et al.", "et al. 2007", "al. 2007 .", "2007 .

monoubiquitinated", ".

monoubiquitinated fancd2", "

monoubiquitinated fancd2 recruits", "fancd2 recruits dna", "recruits dna nucleases", "nucleases including", "slx4 fancp", "fancp and", "fan1 which", "which unhook the", "unhook the icl", "the icl from", "icl from one", "from one of", "one of the", "of the two", "the two covalently", "two covalently linked", "covalently linked dna", "linked dna strands.", "dna strands. the", "strands. the dna", "the dna polymerase", "dna polymerase nu", "nu poln", "poln performs", "performs translesion dna", "translesion dna synthesis", "dna synthesis using", "synthesis using the", "using the dna", "the dna strand", "dna strand with", "strand with unhooked", "with unhooked icl", "unhooked icl as", "icl as a", "as a template", "template thereby", "thereby bypassing the", "bypassing the unhooked", "the unhooked icl.", "unhooked icl. the", "icl. the unhooked", "the unhooked icl", "unhooked icl is", "icl is subsequently", "is subsequently removed", "subsequently removed from", "removed from the", "from the dna", "the dna via", "dna via nucleotide", "via nucleotide excision", "nucleotide excision repair", "repair ner", "ner . incision", ". incision of", "incision of the", "of the stalled", "the stalled replication", "stalled replication fork", "replication fork during", "fork during the", "during the unhooking", "the unhooking step", "unhooking step generates", "step generates a", "generates a double", "a double strand", "double strand break", "break dsb", "dsb . the", ". the dsb", "the dsb is", "dsb is repaired", "is repaired via", "repaired via homologous", "via homologous recombination", "repair hrr", "hrr and", "and involves the", "involves the fa", "the fa genes", "fa genes brca2", "brca2 fancd1", "palb2 fancn", "fancn and", "brip1 fancj", "reviewed by deans", "by deans and", "deans and west", "and west 2011", "2011 kottemann", "kottemann and smogorzewska", "and smogorzewska 2013", "smogorzewska 2013 .", "2013 . homozygous", ". homozygous mutations", "homozygous mutations in", "mutations in brca2", "brca2 palb2", "palb2 or brip1", "or brip1 result", "brip1 result in", "result in fanconi", "in fanconi anemia", "anemia while", "while heterozygous mutations", "heterozygous mutations in", "mutations in these", "in these genes", "these genes predispose", "genes predispose carriers", "predispose carriers to", "carriers to primarily", "to primarily breast", "primarily breast and", "breast and ovarian", "and ovarian cancer.", "ovarian cancer. well", "cancer. well established", "well established functions", "established functions of", "functions of brca2", "palb2 and brip1", "and brip1 in", "brip1 in dna", "in dna repair", "dna repair are", "repair are brca1", "are brca1 dependent", "dependent but", "but it is", "it is not", "is not yet", "not yet clear", "yet clear whether", "clear whether there", "whether there are", "there are additional", "are additional roles", "additional roles for", "roles for these", "for these proteins", "these proteins in", "proteins in the", "in the fanconi", "the fanconi anemia", "anemia pathway that", "pathway that do", "that do not", "do not rely", "not rely on", "rely on brca1", "brca1 evans", "evans and longo", "and longo 2014", "2014 jiang", "jiang and greenberg", "and greenberg 2015", "greenberg 2015 .", "2015 . heterozygous", ". heterozygous brca1", "heterozygous brca1 mutations", "brca1 mutations predispose", "mutations predispose carriers", "carriers to breast", "to breast and", "and ovarian cancer", "ovarian cancer with", "cancer with high", "with high penetrance.", "high penetrance. complete", "penetrance. complete loss", "complete loss of", "loss of brca1", "of brca1 function", "brca1 function is", "function is embryonic", "is embryonic lethal.", "embryonic lethal. it", "lethal. it has", "it has only", "has only recently", "only recently been", "recently been reported", "been reported that", "reported that a", "that a partial", "a partial germline", "partial germline loss", "germline loss of", "brca1 function via", "function via mutations", "via mutations that", "mutations that diminish", "that diminish protein", "diminish protein binding", "protein binding ability", "binding ability of", "ability of the", "of the brct", "the brct domain", "brct domain of", "domain of brca1", "of brca1 result", "brca1 result in", "result in a", "in a fa", "a fa like", "fa like syndrome.", "like syndrome. brca1", "syndrome. brca1 has", "brca1 has therefore", "has therefore been", "therefore been designated", "been designated as", "designated as the", "as the fancs", "the fancs gene", "gene jiang", "greenberg 2015 .

the", "2015 .

the fa", ".

the fa pathway", "pathway is involved", "is involved in", "involved in repairing", "in repairing dna", "repairing dna icls", "dna icls that", "icls that arise", "that arise by", "arise by exposure", "by exposure to", "exposure to endogenous", "to endogenous mutagens", "endogenous mutagens produced", "mutagens produced as", "produced as by", "as by products", "by products of", "products of normal", "of normal cellular", "normal cellular metabolism", "metabolism such", "such as aldehyde", "as aldehyde containing", "aldehyde containing compounds.", "containing compounds. disruption", "compounds. disruption of", "disruption of the", "of the aldehyde", "the aldehyde dehydrogenase", "aldehyde dehydrogenase gene", "dehydrogenase gene aldh2", "gene aldh2 in", "aldh2 in fancd2", "in fancd2 deficient", "fancd2 deficient mice", "deficient mice leads", "mice leads to", "leads to severe", "to severe developmental", "severe developmental defects", "defects early", "early lethality and", "lethality and predisposition", "and predisposition to", "predisposition to leukemia.", "to leukemia. in", "leukemia. in addition", "in addition to", "addition to this", "this the", "the double knockout", "double knockout mice", "knockout mice are", "mice are exceptionally", "are exceptionally sensitive", "exceptionally sensitive to", "sensitive to ethanol", "to ethanol consumption", "consumption as", "as ethanol metabolism", "ethanol metabolism results", "metabolism results in", "results in accumulated", "in accumulated levels", "accumulated levels of", "levels of aldehydes", "aldehydes langevin", "langevin et al.", "et al. 2011", "al. 2011 .", "fanconi anemia fa", "fa is a", "is a genetic disease", "a genetic disease of", "genetic disease of genome", "disease of genome instability", "of genome instability characterized", "genome instability characterized by", "instability characterized by congenital", "characterized by congenital skeletal", "by congenital skeletal defects", "skeletal defects aplastic", "defects aplastic anemia", "aplastic anemia susceptibility", "anemia susceptibility to", "to leukemias and", "leukemias and cellular", "and cellular sensitivity to", "cellular sensitivity to dna", "sensitivity to dna damaging", "to dna damaging agents.", "dna damaging agents. patients", "damaging agents. patients with", "agents. patients with fa", "patients with fa have", "with fa have been", "fa have been categorized", "have been categorized into", "been categorized into at", "categorized into at least", "into at least 15", "at least 15 complementation", "least 15 complementation groups", "complementation groups fa", "groups fa a", "a b", "b c", "c d1", "d1 d2", "d2 e", "e f", "f g", "g i", "i j", "j l", "l m", "m n", "n o", "o and p", "and p .", "p . these complementation", ". these complementation groups", "these complementation groups correspond", "complementation groups correspond to", "groups correspond to the", "correspond to the genes", "to the genes fanca", "genes fanca fancb", "fancn/palb2 fanco/rad51c and", "fanco/rad51c and fancp/slx4. eight", "and fancp/slx4. eight of", "fancp/slx4. eight of these", "eight of these proteins", "these proteins fanca", "fancl and fancm", "and fancm together", "fancm together with", "with faap24 faap100", "faap20 apitd1 and", "and stra13 form", "stra13 form a", "form a nuclear complex", "a nuclear complex termed", "nuclear complex termed the", "complex termed the fa", "termed the fa core", "the fa core complex.", "fa core complex. the", "core complex. the fa", "complex. the fa core", "the fa core complex", "fa core complex is", "core complex is an", "complex is an e3", "is an e3 ubiquitin", "an e3 ubiquitin ligase", "e3 ubiquitin ligase that", "ubiquitin ligase that recognizes", "ligase that recognizes and", "that recognizes and is", "recognizes and is activated", "and is activated by", "is activated by dna", "activated by dna damage", "by dna damage in", "dna damage in the", "damage in the form", "in the form of", "the form of interstrand", "form of interstrand crosslinks", "interstrand crosslinks icls", "icls triggering", "triggering monoubiquitination of fancd2", "monoubiquitination of fancd2 and", "of fancd2 and fanci", "and fanci which", "fanci which initiates", "which initiates repair of", "initiates repair of icl", "repair of icl dna.

fancd2", "of icl dna.

fancd2 and", "icl dna.

fancd2 and fanci", "dna.

fancd2 and fanci form", "and fanci form a", "fanci form a complex", "form a complex and", "a complex and are", "complex and are mutually", "and are mutually dependent", "are mutually dependent on", "mutually dependent on one", "dependent on one another", "on one another for", "one another for their", "another for their respective", "for their respective monoubiquitination.", "their respective monoubiquitination. after", "respective monoubiquitination. after dna", "monoubiquitination. after dna damage", "after dna damage and", "dna damage and during", "damage and during s", "and during s phase", "s phase fancd2", "phase fancd2 localizes", "fancd2 localizes to discrete", "localizes to discrete nuclear", "to discrete nuclear foci", "discrete nuclear foci that", "nuclear foci that colocalize", "foci that colocalize with", "that colocalize with proteins", "colocalize with proteins involved", "with proteins involved in", "proteins involved in homologous", "involved in homologous recombination", "in homologous recombination repair", "recombination repair such", "repair such as", "such as brca1 and", "as brca1 and rad51.", "brca1 and rad51. the", "and rad51. the fa", "rad51. the fa pathway", "the fa pathway is", "fa pathway is regulated", "pathway is regulated by", "is regulated by ubiquitination", "regulated by ubiquitination and", "by ubiquitination and phosphorylation", "ubiquitination and phosphorylation of", "and phosphorylation of fancd2", "phosphorylation of fancd2 and", "of fancd2 and fanci.", "fancd2 and fanci. atr", "and fanci. atr dependent", "fanci. atr dependent phosphorylation", "atr dependent phosphorylation of", "dependent phosphorylation of fanci", "phosphorylation of fanci and", "of fanci and fancd2", "fanci and fancd2 promotes", "and fancd2 promotes monoubiquitination", "fancd2 promotes monoubiquitination of", "promotes monoubiquitination of fancd2", "of fancd2 stimulating", "fancd2 stimulating the", "stimulating the fa pathway", "fa pathway cohn", "pathway cohn and", "cohn and d'andrea 2008", "d'andrea 2008 wang", "2008 wang 2007", "wang 2007 . the", "2007 . the complex", ". the complex of", "the complex of usp1", "complex of usp1 and", "of usp1 and wdr48", "and wdr48 uaf1", "uaf1 is responsible", "is responsible for deubiquitination", "responsible for deubiquitination of", "for deubiquitination of fancd2", "deubiquitination of fancd2 and", "of fancd2 and negatively", "fancd2 and negatively regulates", "and negatively regulates the", "negatively regulates the fa", "regulates the fa pathway", "pathway cohn et", "cohn et al. 2007", "et al. 2007 .", "al. 2007 .

monoubiquitinated", "2007 .

monoubiquitinated fancd2", ".

monoubiquitinated fancd2 recruits", "

monoubiquitinated fancd2 recruits dna", "fancd2 recruits dna nucleases", "dna nucleases including", "nucleases including slx4", "including slx4 fancp", "fancp and fan1", "and fan1 which", "fan1 which unhook", "which unhook the icl", "unhook the icl from", "the icl from one", "icl from one of", "from one of the", "one of the two", "of the two covalently", "the two covalently linked", "two covalently linked dna", "covalently linked dna strands.", "linked dna strands. the", "dna strands. the dna", "strands. the dna polymerase", "the dna polymerase nu", "polymerase nu poln", "poln performs translesion", "performs translesion dna synthesis", "translesion dna synthesis using", "dna synthesis using the", "synthesis using the dna", "using the dna strand", "the dna strand with", "dna strand with unhooked", "strand with unhooked icl", "with unhooked icl as", "unhooked icl as a", "icl as a template", "a template thereby", "template thereby bypassing", "thereby bypassing the unhooked", "bypassing the unhooked icl.", "the unhooked icl. the", "unhooked icl. the unhooked", "icl. the unhooked icl", "the unhooked icl is", "unhooked icl is subsequently", "icl is subsequently removed", "is subsequently removed from", "subsequently removed from the", "removed from the dna", "from the dna via", "the dna via nucleotide", "dna via nucleotide excision", "via nucleotide excision repair", "excision repair ner", "repair ner .", "ner . incision of", ". incision of the", "incision of the stalled", "of the stalled replication", "the stalled replication fork", "stalled replication fork during", "replication fork during the", "fork during the unhooking", "during the unhooking step", "the unhooking step generates", "unhooking step generates a", "step generates a double", "generates a double strand", "a double strand break", "strand break dsb", "break dsb .", "dsb . the dsb", ". the dsb is", "the dsb is repaired", "dsb is repaired via", "is repaired via homologous", "repaired via homologous recombination", "via homologous recombination repair", "recombination repair hrr", "hrr and involves", "and involves the fa", "involves the fa genes", "the fa genes brca2", "genes brca2 fancd1", "fancd1 palb2", "fancn and brip1", "and brip1 fancj", "fancj reviewed", "reviewed by deans and", "by deans and west", "deans and west 2011", "west 2011 kottemann", "2011 kottemann and", "kottemann and smogorzewska 2013", "and smogorzewska 2013 .", "smogorzewska 2013 . homozygous", "2013 . homozygous mutations", ". homozygous mutations in", "homozygous mutations in brca2", "in brca2 palb2", "brca2 palb2 or", "palb2 or brip1 result", "or brip1 result in", "brip1 result in fanconi", "result in fanconi anemia", "fanconi anemia while", "anemia while heterozygous", "while heterozygous mutations in", "heterozygous mutations in these", "mutations in these genes", "in these genes predispose", "these genes predispose carriers", "genes predispose carriers to", "predispose carriers to primarily", "carriers to primarily breast", "to primarily breast and", "primarily breast and ovarian", "breast and ovarian cancer.", "and ovarian cancer. well", "ovarian cancer. well established", "cancer. well established functions", "well established functions of", "established functions of brca2", "of brca2 palb2", "brca2 palb2 and", "palb2 and brip1 in", "and brip1 in dna", "brip1 in dna repair", "in dna repair are", "dna repair are brca1", "repair are brca1 dependent", "brca1 dependent but", "dependent but it", "but it is not", "it is not yet", "is not yet clear", "not yet clear whether", "yet clear whether there", "clear whether there are", "whether there are additional", "there are additional roles", "are additional roles for", "additional roles for these", "roles for these proteins", "for these proteins in", "these proteins in the", "proteins in the fanconi", "in the fanconi anemia", "the fanconi anemia pathway", "fanconi anemia pathway that", "anemia pathway that do", "pathway that do not", "that do not rely", "do not rely on", "not rely on brca1", "on brca1 evans", "brca1 evans and", "evans and longo 2014", "longo 2014 jiang", "2014 jiang and", "jiang and greenberg 2015", "and greenberg 2015 .", "greenberg 2015 . heterozygous", "2015 . heterozygous brca1", ". heterozygous brca1 mutations", "heterozygous brca1 mutations predispose", "brca1 mutations predispose carriers", "mutations predispose carriers to", "predispose carriers to breast", "carriers to breast and", "to breast and ovarian", "breast and ovarian cancer", "and ovarian cancer with", "ovarian cancer with high", "cancer with high penetrance.", "with high penetrance. complete", "high penetrance. complete loss", "penetrance. complete loss of", "complete loss of brca1", "loss of brca1 function", "of brca1 function is", "brca1 function is embryonic", "function is embryonic lethal.", "is embryonic lethal. it", "embryonic lethal. it has", "lethal. it has only", "it has only recently", "has only recently been", "only recently been reported", "recently been reported that", "been reported that a", "reported that a partial", "that a partial germline", "a partial germline loss", "partial germline loss of", "germline loss of brca1", "of brca1 function via", "brca1 function via mutations", "function via mutations that", "via mutations that diminish", "mutations that diminish protein", "that diminish protein binding", "diminish protein binding ability", "protein binding ability of", "binding ability of the", "ability of the brct", "of the brct domain", "the brct domain of", "brct domain of brca1", "domain of brca1 result", "of brca1 result in", "brca1 result in a", "result in a fa", "in a fa like", "a fa like syndrome.", "fa like syndrome. brca1", "like syndrome. brca1 has", "syndrome. brca1 has therefore", "brca1 has therefore been", "has therefore been designated", "therefore been designated as", "been designated as the", "designated as the fancs", "as the fancs gene", "fancs gene jiang", "gene jiang and", "and greenberg 2015 .

the", "greenberg 2015 .

the fa", "2015 .

the fa pathway", ".

the fa pathway is", "fa pathway is involved", "pathway is involved in", "is involved in repairing", "involved in repairing dna", "in repairing dna icls", "repairing dna icls that", "dna icls that arise", "icls that arise by", "that arise by exposure", "arise by exposure to", "by exposure to endogenous", "exposure to endogenous mutagens", "to endogenous mutagens produced", "endogenous mutagens produced as", "mutagens produced as by", "produced as by products", "as by products of", "by products of normal", "products of normal cellular", "of normal cellular metabolism", "cellular metabolism such", "metabolism such as", "such as aldehyde containing", "as aldehyde containing compounds.", "aldehyde containing compounds. disruption", "containing compounds. disruption of", "compounds. disruption of the", "disruption of the aldehyde", "of the aldehyde dehydrogenase", "the aldehyde dehydrogenase gene", "aldehyde dehydrogenase gene aldh2", "dehydrogenase gene aldh2 in", "gene aldh2 in fancd2", "aldh2 in fancd2 deficient", "in fancd2 deficient mice", "fancd2 deficient mice leads", "deficient mice leads to", "mice leads to severe", "leads to severe developmental", "to severe developmental defects", "developmental defects early", "defects early lethality", "early lethality and predisposition", "lethality and predisposition to", "and predisposition to leukemia.", "predisposition to leukemia. in", "to leukemia. in addition", "leukemia. in addition to", "in addition to this", "to this the", "this the double", "the double knockout mice", "double knockout mice are", "knockout mice are exceptionally", "mice are exceptionally sensitive", "are exceptionally sensitive to", "exceptionally sensitive to ethanol", "sensitive to ethanol consumption", "ethanol consumption as", "consumption as ethanol", "as ethanol metabolism results", "ethanol metabolism results in", "metabolism results in accumulated", "results in accumulated levels", "in accumulated levels of", "accumulated levels of aldehydes", "of aldehydes langevin", "aldehydes langevin et", "langevin et al. 2011", "et al. 2011 .", "anemia fa is", "fa is a genetic", "is a genetic disease of", "a genetic disease of genome", "genetic disease of genome instability", "disease of genome instability characterized", "of genome instability characterized by", "genome instability characterized by congenital", "instability characterized by congenital skeletal", "characterized by congenital skeletal defects", "congenital skeletal defects aplastic", "skeletal defects aplastic anemia", "aplastic anemia susceptibility to", "anemia susceptibility to leukemias", "susceptibility to leukemias and", "to leukemias and cellular", "leukemias and cellular sensitivity", "and cellular sensitivity to dna", "cellular sensitivity to dna damaging", "sensitivity to dna damaging agents.", "to dna damaging agents. patients", "dna damaging agents. patients with", "damaging agents. patients with fa", "agents. patients with fa have", "patients with fa have been", "with fa have been categorized", "fa have been categorized into", "have been categorized into at", "been categorized into at least", "categorized into at least 15", "into at least 15 complementation", "at least 15 complementation groups", "15 complementation groups fa", "complementation groups fa a", "fa a b", "n o and", "o and p .", "and p . these", "p . these complementation groups", ". these complementation groups correspond", "these complementation groups correspond to", "complementation groups correspond to the", "groups correspond to the genes", "correspond to the genes fanca", "the genes fanca fancb", "fanca fancb fancc", "fancb fancc fancd1/brca2", "fancc fancd1/brca2 fancd2", "fancd1/brca2 fancd2 fance", "fancd2 fance fancf", "fance fancf fancg", "fancf fancg fancj/brip1", "fancg fancj/brip1 fancl", "fancj/brip1 fancl fancm", "fancl fancm fancn/palb2", "fancm fancn/palb2 fanco/rad51c", "fancn/palb2 fanco/rad51c and fancp/slx4.", "fanco/rad51c and fancp/slx4. eight of", "and fancp/slx4. eight of these", "fancp/slx4. eight of these proteins", "of these proteins fanca", "proteins fanca fancb", "fancb fancc fance", "fancc fance fancf", "fancf fancg fancl", "fancg fancl and", "and fancm together with", "fancm together with faap24", "together with faap24 faap100", "faap24 faap100 faap20", "faap100 faap20 apitd1", "faap20 apitd1 and stra13", "apitd1 and stra13 form", "and stra13 form a", "stra13 form a nuclear", "form a nuclear complex termed", "a nuclear complex termed the", "nuclear complex termed the fa", "complex termed the fa core", "termed the fa core complex.", "the fa core complex. the", "fa core complex. the fa", "core complex. the fa core", "complex. the fa core complex", "the fa core complex is", "fa core complex is an", "core complex is an e3", "complex is an e3 ubiquitin", "is an e3 ubiquitin ligase", "an e3 ubiquitin ligase that", "e3 ubiquitin ligase that recognizes", "ubiquitin ligase that recognizes and", "ligase that recognizes and is", "that recognizes and is activated", "recognizes and is activated by", "and is activated by dna", "is activated by dna damage", "activated by dna damage in", "by dna damage in the", "dna damage in the form", "damage in the form of", "in the form of interstrand", "the form of interstrand crosslinks", "of interstrand crosslinks icls", "icls triggering monoubiquitination", "triggering monoubiquitination of fancd2 and", "monoubiquitination of fancd2 and fanci", "fancd2 and fanci which", "and fanci which initiates", "fanci which initiates repair", "which initiates repair of icl", "initiates repair of icl dna.

fancd2", "repair of icl dna.

fancd2 and", "of icl dna.

fancd2 and fanci", "icl dna.

fancd2 and fanci form", "dna.

fancd2 and fanci form a", "and fanci form a complex", "fanci form a complex and", "form a complex and are", "a complex and are mutually", "complex and are mutually dependent", "and are mutually dependent on", "are mutually dependent on one", "mutually dependent on one another", "dependent on one another for", "on one another for their", "one another for their respective", "another for their respective monoubiquitination.", "for their respective monoubiquitination. after", "their respective monoubiquitination. after dna", "respective monoubiquitination. after dna damage", "monoubiquitination. after dna damage and", "after dna damage and during", "dna damage and during s", "damage and during s phase", "during s phase fancd2", "s phase fancd2 localizes", "phase fancd2 localizes to", "fancd2 localizes to discrete nuclear", "localizes to discrete nuclear foci", "to discrete nuclear foci that", "discrete nuclear foci that colocalize", "nuclear foci that colocalize with", "foci that colocalize with proteins", "that colocalize with proteins involved", "colocalize with proteins involved in", "with proteins involved in homologous", "proteins involved in homologous recombination", "involved in homologous recombination repair", "homologous recombination repair such", "recombination repair such as", "repair such as brca1", "such as brca1 and rad51.", "as brca1 and rad51. the", "brca1 and rad51. the fa", "and rad51. the fa pathway", "rad51. the fa pathway is", "the fa pathway is regulated", "fa pathway is regulated by", "pathway is regulated by ubiquitination", "is regulated by ubiquitination and", "regulated by ubiquitination and phosphorylation", "by ubiquitination and phosphorylation of", "ubiquitination and phosphorylation of fancd2", "and phosphorylation of fancd2 and", "phosphorylation of fancd2 and fanci.", "of fancd2 and fanci. atr", "fancd2 and fanci. atr dependent", "and fanci. atr dependent phosphorylation", "fanci. atr dependent phosphorylation of", "atr dependent phosphorylation of fanci", "dependent phosphorylation of fanci and", "phosphorylation of fanci and fancd2", "of fanci and fancd2 promotes", "fanci and fancd2 promotes monoubiquitination", "and fancd2 promotes monoubiquitination of", "fancd2 promotes monoubiquitination of fancd2", "monoubiquitination of fancd2 stimulating", "of fancd2 stimulating the", "fancd2 stimulating the fa", "the fa pathway cohn", "fa pathway cohn and", "pathway cohn and d'andrea", "and d'andrea 2008 wang", "d'andrea 2008 wang 2007", "2008 wang 2007 .", "wang 2007 . the complex", "2007 . the complex of", ". the complex of usp1", "the complex of usp1 and", "complex of usp1 and wdr48", "usp1 and wdr48 uaf1", "wdr48 uaf1 is", "uaf1 is responsible for", "is responsible for deubiquitination of", "responsible for deubiquitination of fancd2", "for deubiquitination of fancd2 and", "deubiquitination of fancd2 and negatively", "of fancd2 and negatively regulates", "fancd2 and negatively regulates the", "and negatively regulates the fa", "negatively regulates the fa pathway", "fa pathway cohn et", "pathway cohn et al.", "cohn et al. 2007 .", "et al. 2007 .

monoubiquitinated", "al. 2007 .

monoubiquitinated fancd2", "2007 .

monoubiquitinated fancd2 recruits", ".

monoubiquitinated fancd2 recruits dna", "

monoubiquitinated fancd2 recruits dna nucleases", "recruits dna nucleases including", "dna nucleases including slx4", "slx4 fancp and", "and fan1 which unhook", "fan1 which unhook the", "which unhook the icl from", "unhook the icl from one", "the icl from one of", "icl from one of the", "from one of the two", "one of the two covalently", "of the two covalently linked", "the two covalently linked dna", "two covalently linked dna strands.", "covalently linked dna strands. the", "linked dna strands. the dna", "dna strands. the dna polymerase", "strands. the dna polymerase nu", "dna polymerase nu poln", "nu poln performs", "poln performs translesion dna", "performs translesion dna synthesis using", "translesion dna synthesis using the", "dna synthesis using the dna", "synthesis using the dna strand", "using the dna strand with", "the dna strand with unhooked", "dna strand with unhooked icl", "strand with unhooked icl as", "with unhooked icl as a", "unhooked icl as a template", "as a template thereby", "a template thereby bypassing", "template thereby bypassing the", "thereby bypassing the unhooked icl.", "bypassing the unhooked icl. the", "the unhooked icl. the unhooked", "unhooked icl. the unhooked icl", "icl. the unhooked icl is", "the unhooked icl is subsequently", "unhooked icl is subsequently removed", "icl is subsequently removed from", "is subsequently removed from the", "subsequently removed from the dna", "removed from the dna via", "from the dna via nucleotide", "the dna via nucleotide excision", "dna via nucleotide excision repair", "nucleotide excision repair ner", "excision repair ner .", "repair ner . incision", "ner . incision of the", ". incision of the stalled", "incision of the stalled replication", "of the stalled replication fork", "the stalled replication fork during", "stalled replication fork during the", "replication fork during the unhooking", "fork during the unhooking step", "during the unhooking step generates", "the unhooking step generates a", "unhooking step generates a double", "step generates a double strand", "generates a double strand break", "double strand break dsb", "strand break dsb .", "break dsb . the", "dsb . the dsb is", ". the dsb is repaired", "the dsb is repaired via", "dsb is repaired via homologous", "is repaired via homologous recombination", "repaired via homologous recombination repair", "homologous recombination repair hrr", "repair hrr and", "hrr and involves the", "and involves the fa genes", "involves the fa genes brca2", "fa genes brca2 fancd1", "palb2 fancn and", "fancj reviewed by", "reviewed by deans and west", "by deans and west 2011", "and west 2011 kottemann", "west 2011 kottemann and", "2011 kottemann and smogorzewska", "kottemann and smogorzewska 2013 .", "and smogorzewska 2013 . homozygous", "smogorzewska 2013 . homozygous mutations", "2013 . homozygous mutations in", ". homozygous mutations in brca2", "mutations in brca2 palb2", "in brca2 palb2 or", "brca2 palb2 or brip1", "palb2 or brip1 result in", "or brip1 result in fanconi", "brip1 result in fanconi anemia", "in fanconi anemia while", "fanconi anemia while heterozygous", "anemia while heterozygous mutations", "while heterozygous mutations in these", "heterozygous mutations in these genes", "mutations in these genes predispose", "in these genes predispose carriers", "these genes predispose carriers to", "genes predispose carriers to primarily", "predispose carriers to primarily breast", "carriers to primarily breast and", "to primarily breast and ovarian", "primarily breast and ovarian cancer.", "breast and ovarian cancer. well", "and ovarian cancer. well established", "ovarian cancer. well established functions", "cancer. well established functions of", "well established functions of brca2", "functions of brca2 palb2", "of brca2 palb2 and", "brca2 palb2 and brip1", "palb2 and brip1 in dna", "and brip1 in dna repair", "brip1 in dna repair are", "in dna repair are brca1", "dna repair are brca1 dependent", "are brca1 dependent but", "brca1 dependent but it", "dependent but it is", "but it is not yet", "it is not yet clear", "is not yet clear whether", "not yet clear whether there", "yet clear whether there are", "clear whether there are additional", "whether there are additional roles", "there are additional roles for", "are additional roles for these", "additional roles for these proteins", "roles for these proteins in", "for these proteins in the", "these proteins in the fanconi", "proteins in the fanconi anemia", "in the fanconi anemia pathway", "the fanconi anemia pathway that", "fanconi anemia pathway that do", "anemia pathway that do not", "pathway that do not rely", "that do not rely on", "do not rely on brca1", "rely on brca1 evans", "on brca1 evans and", "brca1 evans and longo", "and longo 2014 jiang", "longo 2014 jiang and", "2014 jiang and greenberg", "jiang and greenberg 2015 .", "and greenberg 2015 . heterozygous", "greenberg 2015 . heterozygous brca1", "2015 . heterozygous brca1 mutations", ". heterozygous brca1 mutations predispose", "heterozygous brca1 mutations predispose carriers", "brca1 mutations predispose carriers to", "mutations predispose carriers to breast", "predispose carriers to breast and", "carriers to breast and ovarian", "to breast and ovarian cancer", "breast and ovarian cancer with", "and ovarian cancer with high", "ovarian cancer with high penetrance.", "cancer with high penetrance. complete", "with high penetrance. complete loss", "high penetrance. complete loss of", "penetrance. complete loss of brca1", "complete loss of brca1 function", "loss of brca1 function is", "of brca1 function is embryonic", "brca1 function is embryonic lethal.", "function is embryonic lethal. it", "is embryonic lethal. it has", "embryonic lethal. it has only", "lethal. it has only recently", "it has only recently been", "has only recently been reported", "only recently been reported that", "recently been reported that a", "been reported that a partial", "reported that a partial germline", "that a partial germline loss", "a partial germline loss of", "partial germline loss of brca1", "germline loss of brca1 function", "loss of brca1 function via", "of brca1 function via mutations", "brca1 function via mutations that", "function via mutations that diminish", "via mutations that diminish protein", "mutations that diminish protein binding", "that diminish protein binding ability", "diminish protein binding ability of", "protein binding ability of the", "binding ability of the brct", "ability of the brct domain", "of the brct domain of", "the brct domain of brca1", "brct domain of brca1 result", "domain of brca1 result in", "of brca1 result in a", "brca1 result in a fa", "result in a fa like", "in a fa like syndrome.", "a fa like syndrome. brca1", "fa like syndrome. brca1 has", "like syndrome. brca1 has therefore", "syndrome. brca1 has therefore been", "brca1 has therefore been designated", "has therefore been designated as", "therefore been designated as the", "been designated as the fancs", "designated as the fancs gene", "the fancs gene jiang", "fancs gene jiang and", "gene jiang and greenberg", "jiang and greenberg 2015 .

the", "and greenberg 2015 .

the fa", "greenberg 2015 .

the fa pathway", "2015 .

the fa pathway is", ".

the fa pathway is involved", "fa pathway is involved in", "pathway is involved in repairing", "is involved in repairing dna", "involved in repairing dna icls", "in repairing dna icls that", "repairing dna icls that arise", "dna icls that arise by", "icls that arise by exposure", "that arise by exposure to", "arise by exposure to endogenous", "by exposure to endogenous mutagens", "exposure to endogenous mutagens produced", "to endogenous mutagens produced as", "endogenous mutagens produced as by", "mutagens produced as by products", "produced as by products of", "as by products of normal", "by products of normal cellular", "products of normal cellular metabolism", "normal cellular metabolism such", "cellular metabolism such as", "metabolism such as aldehyde", "such as aldehyde containing compounds.", "as aldehyde containing compounds. disruption", "aldehyde containing compounds. disruption of", "containing compounds. disruption of the", "compounds. disruption of the aldehyde", "disruption of the aldehyde dehydrogenase", "of the aldehyde dehydrogenase gene", "the aldehyde dehydrogenase gene aldh2", "aldehyde dehydrogenase gene aldh2 in", "dehydrogenase gene aldh2 in fancd2", "gene aldh2 in fancd2 deficient", "aldh2 in fancd2 deficient mice", "in fancd2 deficient mice leads", "fancd2 deficient mice leads to", "deficient mice leads to severe", "mice leads to severe developmental", "leads to severe developmental defects", "severe developmental defects early", "developmental defects early lethality", "defects early lethality and", "early lethality and predisposition to", "lethality and predisposition to leukemia.", "and predisposition to leukemia. in", "predisposition to leukemia. in addition", "to leukemia. in addition to", "leukemia. in addition to this", "addition to this the", "to this the double", "this the double knockout", "the double knockout mice are", "double knockout mice are exceptionally", "knockout mice are exceptionally sensitive", "mice are exceptionally sensitive to", "are exceptionally sensitive to ethanol", "exceptionally sensitive to ethanol consumption", "to ethanol consumption as", "ethanol consumption as ethanol", "consumption as ethanol metabolism", "as ethanol metabolism results in", "ethanol metabolism results in accumulated", "metabolism results in accumulated levels", "results in accumulated levels of", "in accumulated levels of aldehydes", "levels of aldehydes langevin", "of aldehydes langevin et", "aldehydes langevin et al.", "langevin et al. 2011 ." ] }, { "record_id": "GLY_000594_1_508", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6783783", "r hsa", "hsa 6783783", "r hsa 6783783" ] }, { "record_id": "GLY_000594_1_508", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 10", "10 signaling", "interleukin 10 signaling", "was originally", "originally described", "described as", "as a", "a factor", "factor named", "named cytokine", "cytokine synthesis", "synthesis inhibitory", "inhibitory factor", "factor that", "inhibited t", "t helper", "1 activation", "activation and", "and th1", "th1 cytokine", "cytokine production", "fiorentino et", "et al.", "al. 1989", "1989 .", ". it", "it was", "was found", "found to", "to be", "be expressed", "expressed by", "by a", "a variety", "variety of", "of cell", "cell types", "types including", "including macrophages", "dendritic cell", "cell subsets", "b cells", "several t", "t cell", "cell subpopulations", "subpopulations including", "including th2", "th2 and", "and t", "t regulatory", "regulatory cells", "and natural", "natural killer", "moore et", "al. 2001", "2001 .", "it is", "is now", "now recognized", "recognized that", "that the", "the biological", "biological effects", "effects of", "of il10", "il10 are", "are directed", "directed at", "at antigen", "antigen presenting", "presenting cells", "such as", "as macrophages", "macrophages and", "and dendritic", "dendritic cells", "its effects", "effects on", "on t", "cell development", "development and", "and differentiation", "differentiation are", "are largely", "largely indirect", "indirect via", "via inhibition", "inhibition of", "of macrophage/dendritic", "macrophage/dendritic cell", "cell activation", "and maturation", "pestka et", "al. 2004", "mocellin et", "2004 .", ". t", "t cells", "cells are", "are thought", "thought to", "be the", "the main", "main source", "source of", "hedrich &", "& bream", "bream 2010", "2010 .", ". il10", "il10 inhibits", "inhibits a", "a broad", "broad spectrum", "spectrum of", "of activated", "activated macrophage/monocyte", "macrophage/monocyte functions", "functions including", "including monokine", "monokine synthesis", "no production", "and expression", "expression of", "of class", "class ii", "ii mhc", "mhc and", "and costimulatory", "costimulatory molecules", "molecules such", "as il12", "il12 and", "and cd80/cd86", "de waal", "waal malefyt", "malefyt et", "al. 1991", "gazzinelli et", "al. 1992", "1992 .", ". studies", "studies with", "with recombinant", "recombinant cytokine", "cytokine and", "and neutralizing", "neutralizing antibodies", "antibodies revealed", "revealed pleiotropic", "pleiotropic activities", "activities of", "il10 on", "on b", "and mast", "mast cells", "al. 1993", "rousset et", "thompson snipes", "snipes et", "and provided", "provided evidence", "evidence for", "for the", "the in", "in vivo", "vivo significance", "significance of", "il10 activities", "ishida et", "1993 .", "il10 antagonizes", "antagonizes the", "the expression", "of mhc", "mhc class", "ii and", "and the", "the co", "co stimulatory", "stimulatory molecules", "molecules cd80/cd86", "cd80/cd86 as", "as well", "well as", "as the", "the pro", "pro inflammatory", "inflammatory cytokines", "cytokines il1beta", "tnfalpha and", "and especially", "especially il12", "d'andrea et", ". the", "biological role", "role of", "il10 is", "is not", "not limited", "limited to", "to inactivation", "inactivation of", "of apcs", "it also", "also enhances", "enhances b", "b cell", "mast cell", "and keratinocyte", "keratinocyte growth/differentiation", "as nk", "nk cell", "cell and", "and cd8+", "cd8+ cytotoxic", "cytotoxic t", "il10 also", "enhances nk", "cell proliferation", "proliferation and/or", "and/or production", "production of", "of ifn", "ifn gamma", "cai et", "al. 1999", "1999 .", "

il10 deficient", "deficient mice", "mice exhibited", "exhibited inflammatory", "inflammatory bowel", "bowel disease", "and other", "other exaggerated", "exaggerated inflammatory", "inflammatory responses", "kuhn et", "berg et", "al. 1995", "indicating a", "a critical", "critical role", "role for", "for il10", "il10 in", "in limiting", "limiting inflammatory", "inflammatory responses.", "responses. dysregulation", "dysregulation of", "is linked", "linked with", "with susceptibility", "susceptibility to", "to numerous", "numerous infectious", "infectious and", "and autoimmune", "autoimmune diseases", "diseases in", "in humans", "humans and", "and mouse", "mouse models", ".

il10", "

il10 signaling", "signaling is", "is initiated", "initiated by", "by binding", "binding of", "of homodimeric", "homodimeric il10", "il10 to", "to the", "the extracellular", "extracellular domains", "domains of", "of two", "two adjoining", "adjoining il10ra", "il10ra molecules.", "molecules. this", "this tetramer", "tetramer then", "then binds", "binds two", "two il10rb", "il10rb chains.", "chains. il10rb", "il10rb cannot", "cannot bind", "bind to", "to il10", "il10 unless", "unless bound", "bound to", "to il10ra", "ding et", "yoon et", "al. 2006", "il10ra without", "without the", "co presence", "presence of", "of il10rb", "il10rb fails", "fails to", "to initiate", "initiate signal", "signal transduction", "kotenko et", "al. 1997", "1997 .

il10", ".

il10 binding", "binding activates", "activates the", "the receptor", "receptor associated", "associated janus", "janus tyrosine", "tyrosine kinases", "jak1 and", "and tyk2", "which are", "are constitutively", "constitutively bound", "to il10r1", "il10r1 and", "and il10r2", "il10r2 respectively.", "respectively. in", "in the", "the classic", "classic model", "model of", "of receptor", "receptor activation", "activation assembly", "assembly of", "of the", "receptor complex", "complex is", "is believed", "believed to", "to enable", "enable jak1/tyk2", "jak1/tyk2 to", "to phosphorylate", "phosphorylate and", "and activate", "activate each", "each other.", "other. alternatively", "alternatively the", "the binding", "il10 may", "may cause", "cause conformational", "conformational changes", "changes that", "that allow", "allow the", "the pseudokinase", "pseudokinase inhibitory", "inhibitory domain", "domain of", "of one", "one jak", "jak kinase", "kinase to", "to move", "move away", "away from", "from the", "the kinase", "kinase domain", "the other", "other jak", "jak within", "within the", "receptor dimer", "dimer jak", "jak complex", "allowing the", "the two", "two kinase", "kinase domains", "domains to", "to interact", "interact and", "and trans", "trans activate", "waters &", "& brooks", "brooks 2015", "2015 .

the", ".

the activated", "activated jak", "jak kinases", "kinases phosphorylate", "phosphorylate the", "the intracellular", "intracellular domains", "the il10r1", "il10r1 chains", "chains on", "on specific", "specific tyrosine", "tyrosine residues.", "residues. these", "these phosphorylated", "phosphorylated tyrosine", "tyrosine residues", "residues and", "and their", "their flanking", "flanking peptide", "peptide sequences", "sequences serve", "serve as", "as temporary", "temporary docking", "docking sites", "sites for", "the latent", "transcription factor", "stat3. stat3", "stat3 transiently", "transiently docks", "docks on", "on the", "il10r1 chain", "chain via", "via its", "its sh2", "sh2 domain", "and is", "is in", "in turn", "turn tyrosine", "tyrosine phosphorylated", "phosphorylated by", "by the", "associated jaks.", "jaks. once", "once activated", "it dissociates", "dissociates from", "dimerizes with", "with other", "other stat3", "stat3 molecules", "and translocates", "translocates to", "the nucleus", "nucleus where", "where it", "it binds", "binds with", "with high", "high affinity", "affinity to", "to stat", "stat binding", "binding elements", "the promoters", "promoters of", "of il", "il 10", "10 inducible", "inducible genes", "donnelly et", "10 il10", "il10 was", "was originally described", "originally described as", "described as a", "as a factor", "a factor named", "factor named cytokine", "named cytokine synthesis", "cytokine synthesis inhibitory", "synthesis inhibitory factor", "inhibitory factor that", "that inhibited", "inhibited t helper", "helper th", "th 1", "1 activation and", "activation and th1", "and th1 cytokine", "th1 cytokine production", "production fiorentino", "fiorentino et al.", "et al. 1989", "al. 1989 .", "1989 . it", ". it was", "it was found", "was found to", "found to be", "to be expressed", "be expressed by", "expressed by a", "by a variety", "a variety of", "variety of cell", "of cell types", "cell types including", "types including macrophages", "macrophages dendritic", "dendritic cell subsets", "subsets b", "cells several", "several t cell", "t cell subpopulations", "cell subpopulations including", "subpopulations including th2", "including th2 and", "th2 and t", "and t regulatory", "t regulatory cells", "cells tregs", "tregs and", "and natural killer", "killer nk", "nk cells", "cells moore", "moore et al.", "et al. 2001", "al. 2001 .", "2001 . it", ". it is", "it is now", "is now recognized", "now recognized that", "recognized that the", "that the biological", "the biological effects", "biological effects of", "effects of il10", "of il10 are", "il10 are directed", "are directed at", "directed at antigen", "at antigen presenting", "antigen presenting cells", "cells apcs", "apcs such", "such as macrophages", "as macrophages and", "macrophages and dendritic", "and dendritic cells", "cells dcs", "its effects on", "effects on t", "on t cell", "t cell development", "cell development and", "development and differentiation", "and differentiation are", "differentiation are largely", "are largely indirect", "largely indirect via", "indirect via inhibition", "via inhibition of", "inhibition of macrophage/dendritic", "of macrophage/dendritic cell", "macrophage/dendritic cell activation", "cell activation and", "activation and maturation", "maturation pestka", "pestka et al.", "et al. 2004", "2004 mocellin", "mocellin et al.", "al. 2004 .", "2004 . t", ". t cells", "t cells are", "cells are thought", "are thought to", "thought to be", "to be the", "be the main", "the main source", "main source of", "source of il10", "il10 hedrich", "hedrich & bream", "& bream 2010", "bream 2010 .", "2010 . il10", ". il10 inhibits", "il10 inhibits a", "inhibits a broad", "a broad spectrum", "broad spectrum of", "spectrum of activated", "of activated macrophage/monocyte", "activated macrophage/monocyte functions", "macrophage/monocyte functions including", "functions including monokine", "including monokine synthesis", "synthesis no", "production and", "and expression of", "expression of class", "of class ii", "class ii mhc", "ii mhc and", "mhc and costimulatory", "and costimulatory molecules", "costimulatory molecules such", "molecules such as", "such as il12", "as il12 and", "il12 and cd80/cd86", "cd80/cd86 de", "de waal malefyt", "waal malefyt et", "malefyt et al.", "et al. 1991", "1991 gazzinelli", "gazzinelli et al.", "et al. 1992", "al. 1992 .", "1992 . studies", ". studies with", "studies with recombinant", "with recombinant cytokine", "recombinant cytokine and", "cytokine and neutralizing", "and neutralizing antibodies", "neutralizing antibodies revealed", "antibodies revealed pleiotropic", "revealed pleiotropic activities", "pleiotropic activities of", "activities of il10", "of il10 on", "il10 on b", "b t", "t and", "and mast cells", "cells de", "et al. 1993", "1993 rousset", "rousset et al.", "1992 thompson", "thompson snipes et", "snipes et al.", "1991 and", "and provided evidence", "provided evidence for", "evidence for the", "for the in", "the in vivo", "in vivo significance", "vivo significance of", "significance of il10", "of il10 activities", "activities ishida", "ishida et al.", "1992 1993", "1993 . il10", ". il10 antagonizes", "il10 antagonizes the", "antagonizes the expression", "the expression of", "expression of mhc", "of mhc class", "mhc class ii", "class ii and", "ii and the", "and the co", "the co stimulatory", "co stimulatory molecules", "stimulatory molecules cd80/cd86", "molecules cd80/cd86 as", "cd80/cd86 as well", "as well as", "well as the", "as the pro", "the pro inflammatory", "pro inflammatory cytokines", "inflammatory cytokines il1beta", "il1beta il6", "il6 il8", "il8 tnfalpha", "tnfalpha and especially", "and especially il12", "il12 fiorentino", "1991 d'andrea", "d'andrea et al.", "al. 1993 .", "1993 . the", ". the biological", "the biological role", "biological role of", "role of il10", "of il10 is", "il10 is not", "is not limited", "not limited to", "limited to inactivation", "to inactivation of", "inactivation of apcs", "apcs it", "it also enhances", "also enhances b", "enhances b cell", "cell granulocyte", "granulocyte mast", "and keratinocyte growth/differentiation", "growth/differentiation as", "well as nk", "as nk cell", "nk cell and", "cell and cd8+", "and cd8+ cytotoxic", "cd8+ cytotoxic t", "cytotoxic t cell", "t cell activation", "activation moore", "2001 hedrich", ". il10 also", "il10 also enhances", "also enhances nk", "enhances nk cell", "nk cell proliferation", "cell proliferation and/or", "proliferation and/or production", "and/or production of", "production of ifn", "of ifn gamma", "gamma cai", "cai et al.", "et al. 1999", "al. 1999 .", "

il10 deficient mice", "deficient mice exhibited", "mice exhibited inflammatory", "exhibited inflammatory bowel", "inflammatory bowel disease", "disease ibd", "ibd and", "and other exaggerated", "other exaggerated inflammatory", "exaggerated inflammatory responses", "responses kuhn", "kuhn et al.", "1993 berg", "berg et al.", "et al. 1995", "1995 indicating", "indicating a critical", "a critical role", "critical role for", "role for il10", "for il10 in", "il10 in limiting", "in limiting inflammatory", "limiting inflammatory responses.", "inflammatory responses. dysregulation", "responses. dysregulation of", "dysregulation of il10", "il10 is linked", "is linked with", "linked with susceptibility", "with susceptibility to", "susceptibility to numerous", "to numerous infectious", "numerous infectious and", "infectious and autoimmune", "and autoimmune diseases", "autoimmune diseases in", "diseases in humans", "in humans and", "humans and mouse", "and mouse models", "models hedrich", "2010 .

il10", ".

il10 signaling", "

il10 signaling is", "signaling is initiated", "is initiated by", "initiated by binding", "by binding of", "binding of homodimeric", "of homodimeric il10", "homodimeric il10 to", "il10 to the", "to the extracellular", "the extracellular domains", "extracellular domains of", "domains of two", "of two adjoining", "two adjoining il10ra", "adjoining il10ra molecules.", "il10ra molecules. this", "molecules. this tetramer", "this tetramer then", "tetramer then binds", "then binds two", "binds two il10rb", "two il10rb chains.", "il10rb chains. il10rb", "chains. il10rb cannot", "il10rb cannot bind", "cannot bind to", "bind to il10", "to il10 unless", "il10 unless bound", "unless bound to", "bound to il10ra", "il10ra ding", "ding et al.", "2001 yoon", "yoon et al.", "et al. 2006", "binding of il10", "of il10 to", "il10 to il10ra", "to il10ra without", "il10ra without the", "without the co", "the co presence", "co presence of", "presence of il10rb", "of il10rb fails", "il10rb fails to", "fails to initiate", "to initiate signal", "initiate signal transduction", "transduction kotenko", "kotenko et al.", "et al. 1997", "al. 1997 .

il10", "1997 .

il10 binding", ".

il10 binding activates", "binding activates the", "activates the receptor", "the receptor associated", "receptor associated janus", "associated janus tyrosine", "janus tyrosine kinases", "kinases jak1", "jak1 and tyk2", "tyk2 which", "which are constitutively", "are constitutively bound", "constitutively bound to", "bound to il10r1", "to il10r1 and", "il10r1 and il10r2", "and il10r2 respectively.", "il10r2 respectively. in", "respectively. in the", "in the classic", "the classic model", "classic model of", "model of receptor", "of receptor activation", "receptor activation assembly", "activation assembly of", "assembly of the", "of the receptor", "the receptor complex", "receptor complex is", "complex is believed", "is believed to", "believed to enable", "to enable jak1/tyk2", "enable jak1/tyk2 to", "jak1/tyk2 to phosphorylate", "to phosphorylate and", "phosphorylate and activate", "and activate each", "activate each other.", "each other. alternatively", "other. alternatively the", "alternatively the binding", "the binding of", "of il10 may", "il10 may cause", "may cause conformational", "cause conformational changes", "conformational changes that", "changes that allow", "that allow the", "allow the pseudokinase", "the pseudokinase inhibitory", "pseudokinase inhibitory domain", "inhibitory domain of", "domain of one", "of one jak", "one jak kinase", "jak kinase to", "kinase to move", "to move away", "move away from", "away from the", "from the kinase", "the kinase domain", "kinase domain of", "domain of the", "of the other", "the other jak", "other jak within", "jak within the", "within the receptor", "the receptor dimer", "receptor dimer jak", "dimer jak complex", "complex allowing", "allowing the two", "the two kinase", "two kinase domains", "kinase domains to", "domains to interact", "to interact and", "interact and trans", "and trans activate", "activate waters", "waters & brooks", "& brooks 2015", "brooks 2015 .

the", "2015 .

the activated", ".

the activated jak", "activated jak kinases", "jak kinases phosphorylate", "kinases phosphorylate the", "phosphorylate the intracellular", "the intracellular domains", "intracellular domains of", "domains of the", "of the il10r1", "the il10r1 chains", "il10r1 chains on", "chains on specific", "on specific tyrosine", "specific tyrosine residues.", "tyrosine residues. these", "residues. these phosphorylated", "these phosphorylated tyrosine", "phosphorylated tyrosine residues", "tyrosine residues and", "residues and their", "and their flanking", "their flanking peptide", "flanking peptide sequences", "peptide sequences serve", "sequences serve as", "serve as temporary", "as temporary docking", "temporary docking sites", "docking sites for", "sites for the", "for the latent", "latent cytosolic", "cytosolic transcription", "factor stat3.", "stat3. stat3 transiently", "stat3 transiently docks", "transiently docks on", "docks on the", "on the il10r1", "the il10r1 chain", "il10r1 chain via", "chain via its", "via its sh2", "its sh2 domain", "domain and", "and is in", "is in turn", "in turn tyrosine", "turn tyrosine phosphorylated", "tyrosine phosphorylated by", "phosphorylated by the", "by the receptor", "receptor associated jaks.", "associated jaks. once", "jaks. once activated", "activated it", "it dissociates from", "dissociates from the", "from the receptor", "receptor dimerizes", "dimerizes with other", "with other stat3", "other stat3 molecules", "molecules and", "and translocates to", "translocates to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it binds", "it binds with", "binds with high", "with high affinity", "high affinity to", "affinity to stat", "to stat binding", "stat binding elements", "elements sbes", "sbes in", "in the promoters", "the promoters of", "promoters of il", "of il 10", "il 10 inducible", "10 inducible genes", "genes donnelly", "donnelly et al.", "interleukin 10 il10", "il10 was originally", "was originally described as", "originally described as a", "described as a factor", "as a factor named", "a factor named cytokine", "factor named cytokine synthesis", "named cytokine synthesis inhibitory", "cytokine synthesis inhibitory factor", "synthesis inhibitory factor that", "factor that inhibited", "that inhibited t", "t helper th", "th 1 activation", "1 activation and th1", "activation and th1 cytokine", "and th1 cytokine production", "cytokine production fiorentino", "production fiorentino et", "fiorentino et al. 1989", "et al. 1989 .", "al. 1989 . it", "1989 . it was", ". it was found", "it was found to", "was found to be", "found to be expressed", "to be expressed by", "be expressed by a", "expressed by a variety", "by a variety of", "a variety of cell", "variety of cell types", "of cell types including", "cell types including macrophages", "including macrophages dendritic", "macrophages dendritic cell", "cell subsets b", "subsets b cells", "b cells several", "cells several t", "several t cell subpopulations", "t cell subpopulations including", "cell subpopulations including th2", "subpopulations including th2 and", "including th2 and t", "th2 and t regulatory", "and t regulatory cells", "regulatory cells tregs", "tregs and natural", "natural killer nk", "cells moore et", "moore et al. 2001", "et al. 2001 .", "al. 2001 . it", "2001 . it is", ". it is now", "it is now recognized", "is now recognized that", "now recognized that the", "recognized that the biological", "that the biological effects", "the biological effects of", "biological effects of il10", "effects of il10 are", "of il10 are directed", "il10 are directed at", "are directed at antigen", "directed at antigen presenting", "at antigen presenting cells", "presenting cells apcs", "apcs such as", "such as macrophages and", "as macrophages and dendritic", "macrophages and dendritic cells", "dendritic cells dcs", "dcs its", "its effects on t", "effects on t cell", "on t cell development", "t cell development and", "cell development and differentiation", "development and differentiation are", "and differentiation are largely", "differentiation are largely indirect", "are largely indirect via", "largely indirect via inhibition", "indirect via inhibition of", "via inhibition of macrophage/dendritic", "inhibition of macrophage/dendritic cell", "of macrophage/dendritic cell activation", "macrophage/dendritic cell activation and", "cell activation and maturation", "and maturation pestka", "maturation pestka et", "pestka et al. 2004", "al. 2004 mocellin", "2004 mocellin et", "mocellin et al. 2004", "et al. 2004 .", "al. 2004 . t", "2004 . t cells", ". t cells are", "t cells are thought", "cells are thought to", "are thought to be", "thought to be the", "to be the main", "be the main source", "the main source of", "main source of il10", "of il10 hedrich", "il10 hedrich &", "hedrich & bream 2010", "& bream 2010 .", "bream 2010 . il10", "2010 . il10 inhibits", ". il10 inhibits a", "il10 inhibits a broad", "inhibits a broad spectrum", "a broad spectrum of", "broad spectrum of activated", "spectrum of activated macrophage/monocyte", "of activated macrophage/monocyte functions", "activated macrophage/monocyte functions including", "macrophage/monocyte functions including monokine", "functions including monokine synthesis", "monokine synthesis no", "synthesis no production", "no production and", "production and expression", "and expression of class", "expression of class ii", "of class ii mhc", "class ii mhc and", "ii mhc and costimulatory", "mhc and costimulatory molecules", "and costimulatory molecules such", "costimulatory molecules such as", "molecules such as il12", "such as il12 and", "as il12 and cd80/cd86", "and cd80/cd86 de", "cd80/cd86 de waal", "de waal malefyt et", "waal malefyt et al.", "malefyt et al. 1991", "al. 1991 gazzinelli", "1991 gazzinelli et", "gazzinelli et al. 1992", "et al. 1992 .", "al. 1992 . studies", "1992 . studies with", ". studies with recombinant", "studies with recombinant cytokine", "with recombinant cytokine and", "recombinant cytokine and neutralizing", "cytokine and neutralizing antibodies", "and neutralizing antibodies revealed", "neutralizing antibodies revealed pleiotropic", "antibodies revealed pleiotropic activities", "revealed pleiotropic activities of", "pleiotropic activities of il10", "activities of il10 on", "of il10 on b", "on b t", "t and mast", "mast cells de", "cells de waal", "malefyt et al. 1993", "al. 1993 rousset", "1993 rousset et", "rousset et al. 1992", "al. 1992 thompson", "1992 thompson snipes", "thompson snipes et al.", "snipes et al. 1991", "al. 1991 and", "1991 and provided", "and provided evidence for", "provided evidence for the", "evidence for the in", "for the in vivo", "the in vivo significance", "in vivo significance of", "vivo significance of il10", "significance of il10 activities", "il10 activities ishida", "activities ishida et", "ishida et al. 1992", "al. 1992 1993", "1992 1993 .", "1993 . il10 antagonizes", ". il10 antagonizes the", "il10 antagonizes the expression", "antagonizes the expression of", "the expression of mhc", "expression of mhc class", "of mhc class ii", "mhc class ii and", "class ii and the", "ii and the co", "and the co stimulatory", "the co stimulatory molecules", "co stimulatory molecules cd80/cd86", "stimulatory molecules cd80/cd86 as", "molecules cd80/cd86 as well", "cd80/cd86 as well as", "as well as the", "well as the pro", "as the pro inflammatory", "the pro inflammatory cytokines", "pro inflammatory cytokines il1beta", "cytokines il1beta il6", "il8 tnfalpha and", "tnfalpha and especially il12", "especially il12 fiorentino", "il12 fiorentino et", "fiorentino et al. 1991", "al. 1991 d'andrea", "1991 d'andrea et", "d'andrea et al. 1993", "et al. 1993 .", "al. 1993 . the", "1993 . the biological", ". the biological role", "the biological role of", "biological role of il10", "role of il10 is", "of il10 is not", "il10 is not limited", "is not limited to", "not limited to inactivation", "limited to inactivation of", "to inactivation of apcs", "of apcs it", "apcs it also", "it also enhances b", "also enhances b cell", "b cell granulocyte", "granulocyte mast cell", "mast cell and", "cell and keratinocyte", "keratinocyte growth/differentiation as", "growth/differentiation as well", "as well as nk", "well as nk cell", "as nk cell and", "nk cell and cd8+", "cell and cd8+ cytotoxic", "and cd8+ cytotoxic t", "cd8+ cytotoxic t cell", "cytotoxic t cell activation", "cell activation moore", "activation moore et", "al. 2001 hedrich", "2001 hedrich &", "2010 . il10 also", ". il10 also enhances", "il10 also enhances nk", "also enhances nk cell", "enhances nk cell proliferation", "nk cell proliferation and/or", "cell proliferation and/or production", "proliferation and/or production of", "and/or production of ifn", "production of ifn gamma", "ifn gamma cai", "gamma cai et", "cai et al. 1999", "et al. 1999 .", "1999 .

il10", ".

il10 deficient", "

il10 deficient mice exhibited", "deficient mice exhibited inflammatory", "mice exhibited inflammatory bowel", "exhibited inflammatory bowel disease", "bowel disease ibd", "ibd and other", "and other exaggerated inflammatory", "other exaggerated inflammatory responses", "inflammatory responses kuhn", "responses kuhn et", "kuhn et al. 1993", "al. 1993 berg", "1993 berg et", "berg et al. 1995", "al. 1995 indicating", "1995 indicating a", "indicating a critical role", "a critical role for", "critical role for il10", "role for il10 in", "for il10 in limiting", "il10 in limiting inflammatory", "in limiting inflammatory responses.", "limiting inflammatory responses. dysregulation", "inflammatory responses. dysregulation of", "responses. dysregulation of il10", "dysregulation of il10 is", "of il10 is linked", "il10 is linked with", "is linked with susceptibility", "linked with susceptibility to", "with susceptibility to numerous", "susceptibility to numerous infectious", "to numerous infectious and", "numerous infectious and autoimmune", "infectious and autoimmune diseases", "and autoimmune diseases in", "autoimmune diseases in humans", "diseases in humans and", "in humans and mouse", "humans and mouse models", "mouse models hedrich", "models hedrich &", "bream 2010 .

il10", "2010 .

il10 signaling", ".

il10 signaling is", "

il10 signaling is initiated", "signaling is initiated by", "is initiated by binding", "initiated by binding of", "by binding of homodimeric", "binding of homodimeric il10", "of homodimeric il10 to", "homodimeric il10 to the", "il10 to the extracellular", "to the extracellular domains", "the extracellular domains of", "extracellular domains of two", "domains of two adjoining", "of two adjoining il10ra", "two adjoining il10ra molecules.", "adjoining il10ra molecules. this", "il10ra molecules. this tetramer", "molecules. this tetramer then", "this tetramer then binds", "tetramer then binds two", "then binds two il10rb", "binds two il10rb chains.", "two il10rb chains. il10rb", "il10rb chains. il10rb cannot", "chains. il10rb cannot bind", "il10rb cannot bind to", "cannot bind to il10", "bind to il10 unless", "to il10 unless bound", "il10 unless bound to", "unless bound to il10ra", "to il10ra ding", "il10ra ding et", "ding et al. 2001", "al. 2001 yoon", "2001 yoon et", "yoon et al. 2006", "2006 binding", "binding of il10 to", "of il10 to il10ra", "il10 to il10ra without", "to il10ra without the", "il10ra without the co", "without the co presence", "the co presence of", "co presence of il10rb", "presence of il10rb fails", "of il10rb fails to", "il10rb fails to initiate", "fails to initiate signal", "to initiate signal transduction", "signal transduction kotenko", "transduction kotenko et", "kotenko et al. 1997", "et al. 1997 .

il10", "al. 1997 .

il10 binding", "1997 .

il10 binding activates", ".

il10 binding activates the", "binding activates the receptor", "activates the receptor associated", "the receptor associated janus", "receptor associated janus tyrosine", "associated janus tyrosine kinases", "tyrosine kinases jak1", "kinases jak1 and", "and tyk2 which", "tyk2 which are", "which are constitutively bound", "are constitutively bound to", "constitutively bound to il10r1", "bound to il10r1 and", "to il10r1 and il10r2", "il10r1 and il10r2 respectively.", "and il10r2 respectively. in", "il10r2 respectively. in the", "respectively. in the classic", "in the classic model", "the classic model of", "classic model of receptor", "model of receptor activation", "of receptor activation assembly", "receptor activation assembly of", "activation assembly of the", "assembly of the receptor", "of the receptor complex", "the receptor complex is", "receptor complex is believed", "complex is believed to", "is believed to enable", "believed to enable jak1/tyk2", "to enable jak1/tyk2 to", "enable jak1/tyk2 to phosphorylate", "jak1/tyk2 to phosphorylate and", "to phosphorylate and activate", "phosphorylate and activate each", "and activate each other.", "activate each other. alternatively", "each other. alternatively the", "other. alternatively the binding", "alternatively the binding of", "the binding of il10", "binding of il10 may", "of il10 may cause", "il10 may cause conformational", "may cause conformational changes", "cause conformational changes that", "conformational changes that allow", "changes that allow the", "that allow the pseudokinase", "allow the pseudokinase inhibitory", "the pseudokinase inhibitory domain", "pseudokinase inhibitory domain of", "inhibitory domain of one", "domain of one jak", "of one jak kinase", "one jak kinase to", "jak kinase to move", "kinase to move away", "to move away from", "move away from the", "away from the kinase", "from the kinase domain", "the kinase domain of", "kinase domain of the", "domain of the other", "of the other jak", "the other jak within", "other jak within the", "jak within the receptor", "within the receptor dimer", "the receptor dimer jak", "receptor dimer jak complex", "jak complex allowing", "complex allowing the", "allowing the two kinase", "the two kinase domains", "two kinase domains to", "kinase domains to interact", "domains to interact and", "to interact and trans", "interact and trans activate", "trans activate waters", "activate waters &", "waters & brooks 2015", "& brooks 2015 .

the", "brooks 2015 .

the activated", "2015 .

the activated jak", ".

the activated jak kinases", "activated jak kinases phosphorylate", "jak kinases phosphorylate the", "kinases phosphorylate the intracellular", "phosphorylate the intracellular domains", "the intracellular domains of", "intracellular domains of the", "domains of the il10r1", "of the il10r1 chains", "the il10r1 chains on", "il10r1 chains on specific", "chains on specific tyrosine", "on specific tyrosine residues.", "specific tyrosine residues. these", "tyrosine residues. these phosphorylated", "residues. these phosphorylated tyrosine", "these phosphorylated tyrosine residues", "phosphorylated tyrosine residues and", "tyrosine residues and their", "residues and their flanking", "and their flanking peptide", "their flanking peptide sequences", "flanking peptide sequences serve", "peptide sequences serve as", "sequences serve as temporary", "serve as temporary docking", "as temporary docking sites", "temporary docking sites for", "docking sites for the", "sites for the latent", "the latent cytosolic", "cytosolic transcription factor", "transcription factor stat3.", "factor stat3. stat3", "stat3. stat3 transiently docks", "stat3 transiently docks on", "transiently docks on the", "docks on the il10r1", "on the il10r1 chain", "the il10r1 chain via", "il10r1 chain via its", "chain via its sh2", "via its sh2 domain", "sh2 domain and", "domain and is", "and is in turn", "is in turn tyrosine", "in turn tyrosine phosphorylated", "turn tyrosine phosphorylated by", "tyrosine phosphorylated by the", "phosphorylated by the receptor", "by the receptor associated", "the receptor associated jaks.", "receptor associated jaks. once", "associated jaks. once activated", "once activated it", "activated it dissociates", "it dissociates from the", "dissociates from the receptor", "the receptor dimerizes", "receptor dimerizes with", "dimerizes with other stat3", "with other stat3 molecules", "stat3 molecules and", "molecules and translocates", "and translocates to the", "translocates to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it binds", "where it binds with", "it binds with high", "binds with high affinity", "with high affinity to", "high affinity to stat", "affinity to stat binding", "to stat binding elements", "binding elements sbes", "sbes in the", "in the promoters of", "the promoters of il", "promoters of il 10", "of il 10 inducible", "il 10 inducible genes", "inducible genes donnelly", "genes donnelly et", "donnelly et al. 1999", "10 il10 was", "il10 was originally described", "was originally described as a", "originally described as a factor", "described as a factor named", "as a factor named cytokine", "a factor named cytokine synthesis", "factor named cytokine synthesis inhibitory", "named cytokine synthesis inhibitory factor", "cytokine synthesis inhibitory factor that", "inhibitory factor that inhibited", "factor that inhibited t", "that inhibited t helper", "inhibited t helper th", "helper th 1", "th 1 activation and", "1 activation and th1 cytokine", "activation and th1 cytokine production", "th1 cytokine production fiorentino", "cytokine production fiorentino et", "production fiorentino et al.", "fiorentino et al. 1989 .", "et al. 1989 . it", "al. 1989 . it was", "1989 . it was found", ". it was found to", "it was found to be", "was found to be expressed", "found to be expressed by", "to be expressed by a", "be expressed by a variety", "expressed by a variety of", "by a variety of cell", "a variety of cell types", "variety of cell types including", "of cell types including macrophages", "types including macrophages dendritic", "including macrophages dendritic cell", "macrophages dendritic cell subsets", "dendritic cell subsets b", "cell subsets b cells", "b cells several t", "cells several t cell", "several t cell subpopulations including", "t cell subpopulations including th2", "cell subpopulations including th2 and", "subpopulations including th2 and t", "including th2 and t regulatory", "th2 and t regulatory cells", "t regulatory cells tregs", "cells tregs and", "tregs and natural killer", "and natural killer nk", "killer nk cells", "nk cells moore", "cells moore et al.", "moore et al. 2001 .", "et al. 2001 . it", "al. 2001 . it is", "2001 . it is now", ". it is now recognized", "it is now recognized that", "is now recognized that the", "now recognized that the biological", "recognized that the biological effects", "that the biological effects of", "the biological effects of il10", "biological effects of il10 are", "effects of il10 are directed", "of il10 are directed at", "il10 are directed at antigen", "are directed at antigen presenting", "directed at antigen presenting cells", "antigen presenting cells apcs", "cells apcs such", "apcs such as macrophages", "such as macrophages and dendritic", "as macrophages and dendritic cells", "and dendritic cells dcs", "dcs its effects", "its effects on t cell", "effects on t cell development", "on t cell development and", "t cell development and differentiation", "cell development and differentiation are", "development and differentiation are largely", "and differentiation are largely indirect", "differentiation are largely indirect via", "are largely indirect via inhibition", "largely indirect via inhibition of", "indirect via inhibition of macrophage/dendritic", "via inhibition of macrophage/dendritic cell", "inhibition of macrophage/dendritic cell activation", "of macrophage/dendritic cell activation and", "macrophage/dendritic cell activation and maturation", "activation and maturation pestka", "and maturation pestka et", "maturation pestka et al.", "et al. 2004 mocellin", "al. 2004 mocellin et", "2004 mocellin et al.", "mocellin et al. 2004 .", "et al. 2004 . t", "al. 2004 . t cells", "2004 . t cells are", ". t cells are thought", "t cells are thought to", "cells are thought to be", "are thought to be the", "thought to be the main", "to be the main source", "be the main source of", "the main source of il10", "source of il10 hedrich", "of il10 hedrich &", "il10 hedrich & bream", "hedrich & bream 2010 .", "& bream 2010 . il10", "bream 2010 . il10 inhibits", "2010 . il10 inhibits a", ". il10 inhibits a broad", "il10 inhibits a broad spectrum", "inhibits a broad spectrum of", "a broad spectrum of activated", "broad spectrum of activated macrophage/monocyte", "spectrum of activated macrophage/monocyte functions", "of activated macrophage/monocyte functions including", "activated macrophage/monocyte functions including monokine", "macrophage/monocyte functions including monokine synthesis", "including monokine synthesis no", "monokine synthesis no production", "no production and expression", "production and expression of", "and expression of class ii", "expression of class ii mhc", "of class ii mhc and", "class ii mhc and costimulatory", "ii mhc and costimulatory molecules", "mhc and costimulatory molecules such", "and costimulatory molecules such as", "costimulatory molecules such as il12", "molecules such as il12 and", "such as il12 and cd80/cd86", "il12 and cd80/cd86 de", "and cd80/cd86 de waal", "cd80/cd86 de waal malefyt", "de waal malefyt et al.", "waal malefyt et al. 1991", "et al. 1991 gazzinelli", "al. 1991 gazzinelli et", "1991 gazzinelli et al.", "gazzinelli et al. 1992 .", "et al. 1992 . studies", "al. 1992 . studies with", "1992 . studies with recombinant", ". studies with recombinant cytokine", "studies with recombinant cytokine and", "with recombinant cytokine and neutralizing", "recombinant cytokine and neutralizing antibodies", "cytokine and neutralizing antibodies revealed", "and neutralizing antibodies revealed pleiotropic", "neutralizing antibodies revealed pleiotropic activities", "antibodies revealed pleiotropic activities of", "revealed pleiotropic activities of il10", "pleiotropic activities of il10 on", "activities of il10 on b", "il10 on b t", "b t and", "t and mast cells", "and mast cells de", "mast cells de waal", "cells de waal malefyt", "waal malefyt et al. 1993", "et al. 1993 rousset", "al. 1993 rousset et", "1993 rousset et al.", "et al. 1992 thompson", "al. 1992 thompson snipes", "1992 thompson snipes et", "thompson snipes et al. 1991", "et al. 1991 and", "al. 1991 and provided", "1991 and provided evidence", "and provided evidence for the", "provided evidence for the in", "evidence for the in vivo", "for the in vivo significance", "the in vivo significance of", "in vivo significance of il10", "vivo significance of il10 activities", "of il10 activities ishida", "il10 activities ishida et", "activities ishida et al.", "et al. 1992 1993", "al. 1992 1993 .", "1992 1993 . il10", "1993 . il10 antagonizes the", ". il10 antagonizes the expression", "il10 antagonizes the expression of", "antagonizes the expression of mhc", "the expression of mhc class", "expression of mhc class ii", "of mhc class ii and", "mhc class ii and the", "class ii and the co", "ii and the co stimulatory", "and the co stimulatory molecules", "the co stimulatory molecules cd80/cd86", "co stimulatory molecules cd80/cd86 as", "stimulatory molecules cd80/cd86 as well", "molecules cd80/cd86 as well as", "cd80/cd86 as well as the", "as well as the pro", "well as the pro inflammatory", "as the pro inflammatory cytokines", "the pro inflammatory cytokines il1beta", "inflammatory cytokines il1beta il6", "il1beta il6 il8", "il6 il8 tnfalpha", "il8 tnfalpha and especially", "and especially il12 fiorentino", "especially il12 fiorentino et", "il12 fiorentino et al.", "et al. 1991 d'andrea", "al. 1991 d'andrea et", "1991 d'andrea et al.", "d'andrea et al. 1993 .", "et al. 1993 . the", "al. 1993 . the biological", "1993 . the biological role", ". the biological role of", "the biological role of il10", "biological role of il10 is", "role of il10 is not", "of il10 is not limited", "il10 is not limited to", "is not limited to inactivation", "not limited to inactivation of", "limited to inactivation of apcs", "inactivation of apcs it", "of apcs it also", "apcs it also enhances", "it also enhances b cell", "enhances b cell granulocyte", "cell granulocyte mast", "mast cell and keratinocyte", "cell and keratinocyte growth/differentiation", "and keratinocyte growth/differentiation as", "keratinocyte growth/differentiation as well", "growth/differentiation as well as", "as well as nk cell", "well as nk cell and", "as nk cell and cd8+", "nk cell and cd8+ cytotoxic", "cell and cd8+ cytotoxic t", "and cd8+ cytotoxic t cell", "cd8+ cytotoxic t cell activation", "t cell activation moore", "cell activation moore et", "activation moore et al.", "et al. 2001 hedrich", "al. 2001 hedrich &", "2001 hedrich & bream", "bream 2010 . il10 also", "2010 . il10 also enhances", ". il10 also enhances nk", "il10 also enhances nk cell", "also enhances nk cell proliferation", "enhances nk cell proliferation and/or", "nk cell proliferation and/or production", "cell proliferation and/or production of", "proliferation and/or production of ifn", "and/or production of ifn gamma", "of ifn gamma cai", "ifn gamma cai et", "gamma cai et al.", "cai et al. 1999 .", "al. 1999 .

il10", "1999 .

il10 deficient", ".

il10 deficient mice", "

il10 deficient mice exhibited inflammatory", "deficient mice exhibited inflammatory bowel", "mice exhibited inflammatory bowel disease", "inflammatory bowel disease ibd", "disease ibd and", "ibd and other exaggerated", "and other exaggerated inflammatory responses", "exaggerated inflammatory responses kuhn", "inflammatory responses kuhn et", "responses kuhn et al.", "et al. 1993 berg", "al. 1993 berg et", "1993 berg et al.", "et al. 1995 indicating", "al. 1995 indicating a", "1995 indicating a critical", "indicating a critical role for", "a critical role for il10", "critical role for il10 in", "role for il10 in limiting", "for il10 in limiting inflammatory", "il10 in limiting inflammatory responses.", "in limiting inflammatory responses. dysregulation", "limiting inflammatory responses. dysregulation of", "inflammatory responses. dysregulation of il10", "responses. dysregulation of il10 is", "dysregulation of il10 is linked", "of il10 is linked with", "il10 is linked with susceptibility", "is linked with susceptibility to", "linked with susceptibility to numerous", "with susceptibility to numerous infectious", "susceptibility to numerous infectious and", "to numerous infectious and autoimmune", "numerous infectious and autoimmune diseases", "infectious and autoimmune diseases in", "and autoimmune diseases in humans", "autoimmune diseases in humans and", "diseases in humans and mouse", "in humans and mouse models", "and mouse models hedrich", "mouse models hedrich &", "models hedrich & bream", "& bream 2010 .

il10", "bream 2010 .

il10 signaling", "2010 .

il10 signaling is", ".

il10 signaling is initiated", "

il10 signaling is initiated by", "signaling is initiated by binding", "is initiated by binding of", "initiated by binding of homodimeric", "by binding of homodimeric il10", "binding of homodimeric il10 to", "of homodimeric il10 to the", "homodimeric il10 to the extracellular", "il10 to the extracellular domains", "to the extracellular domains of", "the extracellular domains of two", "extracellular domains of two adjoining", "domains of two adjoining il10ra", "of two adjoining il10ra molecules.", "two adjoining il10ra molecules. this", "adjoining il10ra molecules. this tetramer", "il10ra molecules. this tetramer then", "molecules. this tetramer then binds", "this tetramer then binds two", "tetramer then binds two il10rb", "then binds two il10rb chains.", "binds two il10rb chains. il10rb", "two il10rb chains. il10rb cannot", "il10rb chains. il10rb cannot bind", "chains. il10rb cannot bind to", "il10rb cannot bind to il10", "cannot bind to il10 unless", "bind to il10 unless bound", "to il10 unless bound to", "il10 unless bound to il10ra", "bound to il10ra ding", "to il10ra ding et", "il10ra ding et al.", "et al. 2001 yoon", "al. 2001 yoon et", "2001 yoon et al.", "al. 2006 binding", "2006 binding of", "binding of il10 to il10ra", "of il10 to il10ra without", "il10 to il10ra without the", "to il10ra without the co", "il10ra without the co presence", "without the co presence of", "the co presence of il10rb", "co presence of il10rb fails", "presence of il10rb fails to", "of il10rb fails to initiate", "il10rb fails to initiate signal", "fails to initiate signal transduction", "initiate signal transduction kotenko", "signal transduction kotenko et", "transduction kotenko et al.", "kotenko et al. 1997 .

il10", "et al. 1997 .

il10 binding", "al. 1997 .

il10 binding activates", "1997 .

il10 binding activates the", ".

il10 binding activates the receptor", "binding activates the receptor associated", "activates the receptor associated janus", "the receptor associated janus tyrosine", "receptor associated janus tyrosine kinases", "janus tyrosine kinases jak1", "tyrosine kinases jak1 and", "kinases jak1 and tyk2", "jak1 and tyk2 which", "and tyk2 which are", "tyk2 which are constitutively", "which are constitutively bound to", "are constitutively bound to il10r1", "constitutively bound to il10r1 and", "bound to il10r1 and il10r2", "to il10r1 and il10r2 respectively.", "il10r1 and il10r2 respectively. in", "and il10r2 respectively. in the", "il10r2 respectively. in the classic", "respectively. in the classic model", "in the classic model of", "the classic model of receptor", "classic model of receptor activation", "model of receptor activation assembly", "of receptor activation assembly of", "receptor activation assembly of the", "activation assembly of the receptor", "assembly of the receptor complex", "of the receptor complex is", "the receptor complex is believed", "receptor complex is believed to", "complex is believed to enable", "is believed to enable jak1/tyk2", "believed to enable jak1/tyk2 to", "to enable jak1/tyk2 to phosphorylate", "enable jak1/tyk2 to phosphorylate and", "jak1/tyk2 to phosphorylate and activate", "to phosphorylate and activate each", "phosphorylate and activate each other.", "and activate each other. alternatively", "activate each other. alternatively the", "each other. alternatively the binding", "other. alternatively the binding of", "alternatively the binding of il10", "the binding of il10 may", "binding of il10 may cause", "of il10 may cause conformational", "il10 may cause conformational changes", "may cause conformational changes that", "cause conformational changes that allow", "conformational changes that allow the", "changes that allow the pseudokinase", "that allow the pseudokinase inhibitory", "allow the pseudokinase inhibitory domain", "the pseudokinase inhibitory domain of", "pseudokinase inhibitory domain of one", "inhibitory domain of one jak", "domain of one jak kinase", "of one jak kinase to", "one jak kinase to move", "jak kinase to move away", "kinase to move away from", "to move away from the", "move away from the kinase", "away from the kinase domain", "from the kinase domain of", "the kinase domain of the", "kinase domain of the other", "domain of the other jak", "of the other jak within", "the other jak within the", "other jak within the receptor", "jak within the receptor dimer", "within the receptor dimer jak", "the receptor dimer jak complex", "dimer jak complex allowing", "jak complex allowing the", "complex allowing the two", "allowing the two kinase domains", "the two kinase domains to", "two kinase domains to interact", "kinase domains to interact and", "domains to interact and trans", "to interact and trans activate", "and trans activate waters", "trans activate waters &", "activate waters & brooks", "waters & brooks 2015 .

the", "& brooks 2015 .

the activated", "brooks 2015 .

the activated jak", "2015 .

the activated jak kinases", ".

the activated jak kinases phosphorylate", "activated jak kinases phosphorylate the", "jak kinases phosphorylate the intracellular", "kinases phosphorylate the intracellular domains", "phosphorylate the intracellular domains of", "the intracellular domains of the", "intracellular domains of the il10r1", "domains of the il10r1 chains", "of the il10r1 chains on", "the il10r1 chains on specific", "il10r1 chains on specific tyrosine", "chains on specific tyrosine residues.", "on specific tyrosine residues. these", "specific tyrosine residues. these phosphorylated", "tyrosine residues. these phosphorylated tyrosine", "residues. these phosphorylated tyrosine residues", "these phosphorylated tyrosine residues and", "phosphorylated tyrosine residues and their", "tyrosine residues and their flanking", "residues and their flanking peptide", "and their flanking peptide sequences", "their flanking peptide sequences serve", "flanking peptide sequences serve as", "peptide sequences serve as temporary", "sequences serve as temporary docking", "serve as temporary docking sites", "as temporary docking sites for", "temporary docking sites for the", "docking sites for the latent", "for the latent cytosolic", "latent cytosolic transcription", "transcription factor stat3. stat3", "factor stat3. stat3 transiently", "stat3. stat3 transiently docks on", "stat3 transiently docks on the", "transiently docks on the il10r1", "docks on the il10r1 chain", "on the il10r1 chain via", "the il10r1 chain via its", "il10r1 chain via its sh2", "chain via its sh2 domain", "its sh2 domain and", "sh2 domain and is", "domain and is in", "and is in turn tyrosine", "is in turn tyrosine phosphorylated", "in turn tyrosine phosphorylated by", "turn tyrosine phosphorylated by the", "tyrosine phosphorylated by the receptor", "phosphorylated by the receptor associated", "by the receptor associated jaks.", "the receptor associated jaks. once", "receptor associated jaks. once activated", "jaks. once activated it", "once activated it dissociates", "activated it dissociates from", "it dissociates from the receptor", "from the receptor dimerizes", "the receptor dimerizes with", "receptor dimerizes with other", "dimerizes with other stat3 molecules", "other stat3 molecules and", "stat3 molecules and translocates", "molecules and translocates to", "and translocates to the nucleus", "translocates to the nucleus where", "to the nucleus where it", "the nucleus where it binds", "nucleus where it binds with", "where it binds with high", "it binds with high affinity", "binds with high affinity to", "with high affinity to stat", "high affinity to stat binding", "affinity to stat binding elements", "stat binding elements sbes", "elements sbes in", "sbes in the promoters", "in the promoters of il", "the promoters of il 10", "promoters of il 10 inducible", "of il 10 inducible genes", "10 inducible genes donnelly", "inducible genes donnelly et", "genes donnelly et al.", "donnelly et al. 1999 ." ] }, { "record_id": "GLY_000594_1_509", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6784531", "r hsa", "hsa 6784531", "r hsa 6784531" ] }, { "record_id": "GLY_000594_1_509", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "trna processing", "processing in", "in the", "the nucleus", "trna processing in", "processing in the", "in the nucleus", "trna processing in the", "processing in the nucleus", "trna processing in the nucleus", "genes encoding", "encoding transfer", "transfer rnas", "rnas are", "are transcribed", "transcribed in", "nucleus by", "by rna", "rna polymerase", "polymerase iii.", "distinct processes", "processes of", "of transcription", "transcription and", "and processing", "processing also", "also occur", "occur in", "in mitochondria.", "the initial", "initial transcripts", "pre trnas", "contain extra", "extra nucleotides", "nucleotides at", "at the", "the 5'", "5' end", "end and", "and 3'", "3' end.", "end. 6.3%", "32 of", "of 509", "of human", "human trnas", "trnas also", "also contain", "contain introns", "which are", "are located", "located in", "the anticodon", "anticodon loop", "3' to", "to the", "the anticodon.", "anticodon. the", "the additional", "additional nucleotides", "nucleotides are", "are removed", "removed and", "and a", "a non", "non templated", "templated cca", "cca sequence", "sequence is", "is added", "added to", "the resulting", "resulting 3'", "3' terminus", "terminus by", "by processing", "processing reactions", "reactions in", "nucleus and", "and cytosol", "reviewed in", "in nakanishi", "nakanishi and", "and nureki", "nureki 2005", "phizicky and", "and hopper", "hopper 2010", "2010 .
the", ".
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the 3' trailer", "3' trailer is", "trailer is then", "is then removed", "then removed by", "removed by rnase", "by rnase z", "rnase z activity", "activity a", "a single protein", "single protein in", "protein in humans", "humans reviewed", "reviewed in maraia", "in maraia and", "maraia and lamichhane", "and lamichhane 2011", "lamichhane 2011 .", "2011 . elac2", ". elac2 is", "elac2 is a", "is a rnase", "a rnase z", "rnase z found", "z found in", "found in both", "in both nucleus", "both nucleus and", "nucleus and mitochondria.", "and mitochondria. elac1", "mitochondria. elac1 is", "elac1 is found", "is found in", "found in the", "in the cytosol", "the cytosol and", "cytosol and may", "and may also", "may also act", "also act as", "act as an", "as an rnase", "an rnase z.", "rnase z. human", "z. human trna", "human trna genes", "trna genes do", "genes do not", "do not encode", "not encode the", "encode the universal", "the universal acceptor", "universal acceptor 3'", "acceptor 3' terminus", "3' terminus cca", "cca instead", "instead it is", "it is added", "is added post", "added post transcriptionally", "post transcriptionally by", "transcriptionally by trnt1", "trnt1 an", "an unusual polymerase", "unusual polymerase that", "polymerase that requires", "that requires no", "requires no nucleic", "no nucleic acid", "nucleic acid template", "template reviewed", "reviewed in xiong", "in xiong and", "xiong and steitz", "and steitz 2006", "2006 hou", "2010 tomita", "tomita and yamashita", "and yamashita 2014", "yamashita 2014 .
in", "2014 .
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in humans introns", "humans introns are", "introns are spliced", "are spliced from", "spliced from intron", "from intron containing", "intron containing trnas", "containing trnas in", "trnas in the", "nucleus by a", "by a two", "a two step", "two step mechanism", "step mechanism that", "mechanism that is", "that is distinct", "is distinct from", "distinct from mrna", "from mrna splicing", "splicing reviewed", "reviewed in popow", "in popow et", "popow et al.", "et al. 2012", "2012 lopes", "lopes et al.", "et al. 2015", "al. 2015 .", "2015 . the", ". the tsen", "the tsen complex", "tsen complex first", "complex first cleaves", "first cleaves 5'", "cleaves 5' and", "5' and 3'", "and 3' to", "to the intron", "intron generating", "generating a 2'3'", "a 2'3' cyclic", "2'3' cyclic phosphate", "cyclic phosphate on", "phosphate on the", "on the 5'", "the 5' exon", "5' exon and", "exon and a", "and a 5'", "a 5' hydroxyl", "5' hydroxyl group", "hydroxyl group on", "group on the", "on the 3'", "the 3' exon.", "3' exon. these", "exon. these two", "these two ends", "two ends are", "ends are ligated", "are ligated by", "ligated by a", "by a complex", "a complex containing", "complex containing at", "containing at least", "at least 6", "least 6 proteins", "6 proteins in", "proteins in a", "in a single", "a single reaction", "single reaction that", "reaction that both", "that both hydrolyzes", "both hydrolyzes the", "hydrolyzes the 2'", "the 2' phosphate", "2' phosphate bond", "phosphate bond and", "bond and joins", "and joins the", "joins the 3'", "the 3' phosphate", "3' phosphate to", "phosphate to the", "to the 5'", "the 5' hydroxyl.", "hydroxyl. in", "in yeast the", "yeast the ligation", "the ligation and", "ligation and the", "and the hydrolysis", "the hydrolysis of", "hydrolysis of the", "of the 2'", "2' phosphate are", "phosphate are separate", "are separate reactions.", "separate reactions. the", "reactions. the splicing", "the splicing reactions", "splicing reactions in", "reactions in yeast", "in yeast occur", "yeast occur in", "occur in the", "the cytosol at", "cytosol at the", "at the mitochondrial", "the mitochondrial outer", "mitochondrial outer membrane.", "membrane.
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mature transfer rnas", "transfer rnas contain", "rnas contain a", "contain a large", "a large number", "large number of", "number of modified", "of modified nucleotide", "modified nucleotide residues", "nucleotide residues that", "residues that are", "that are produced", "are produced by", "produced by post", "by post transcriptional", "post transcriptional modification", "transcriptional modification reactions", "reactions reviewed", "reviewed in li", "in li and", "li and mason", "and mason 2014", "mason 2014 .", "2014 . depending", ". depending on", "depending on the", "on the specific", "the specific trna", "specific trna these", "trna these reactions", "these reactions may", "reactions may occur", "may occur before", "occur before or", "before or after", "or after splicing", "after splicing and", "splicing and before", "and before or", "or after export", "after export from", "export from the", "from the nucleus", "the nucleus to", "nucleus to the", "to the cytosol.", "genes encoding transfer rnas", "encoding transfer rnas are", "transfer rnas are transcribed", "rnas are transcribed in", "are transcribed in the", "transcribed in the nucleus", "in the nucleus by", "the nucleus by rna", "nucleus by rna polymerase", "by rna polymerase iii.", "polymerase iii. distinct", "iii. distinct processes", "distinct processes of transcription", "processes of transcription and", "of transcription and processing", "transcription and processing also", "and processing also occur", "processing also occur in", "also occur in mitochondria.", "in mitochondria. the", "mitochondria. the initial", "initial transcripts pre", "transcripts pre trnas", "pre trnas contain", "trnas contain extra", "contain extra nucleotides at", "extra nucleotides at the", "nucleotides at the 5'", "at the 5' end", "the 5' end and", "5' end and 3'", "end and 3' end.", "and 3' end. 6.3%", "end. 6.3% 32", "6.3% 32 of", "of 509 of", "509 of human", "of human trnas also", "human trnas also contain", "trnas also contain introns", "contain introns which", "introns which are", "which are located in", "are located in the", "located in the anticodon", "in the anticodon loop", "anticodon loop 3'", "loop 3' to", "3' to the anticodon.", "to the anticodon. the", "the anticodon. the additional", "anticodon. the additional nucleotides", "the additional nucleotides are", "additional nucleotides are removed", "nucleotides are removed and", "are removed and a", "removed and a non", "and a non templated", "a non templated cca", "non templated cca sequence", "templated cca sequence is", "cca sequence is added", "sequence is added to", "is added to the", "added to the resulting", "to the resulting 3'", "the resulting 3' terminus", "resulting 3' terminus by", "3' terminus by processing", "terminus by processing reactions", "by processing reactions in", "processing reactions in the", "reactions in the nucleus", "in the nucleus and", "the nucleus and cytosol", "and cytosol reviewed", "cytosol reviewed in", "reviewed in nakanishi and", "in nakanishi and nureki", "nakanishi and nureki 2005", "nureki 2005 phizicky", "2005 phizicky and", "phizicky and hopper 2010", "and hopper 2010 .
the", "hopper 2010 .
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the 3' trailer is", "3' trailer is then", "trailer is then removed", "is then removed by", "then removed by rnase", "removed by rnase z", "by rnase z activity", "z activity a", "activity a single", "a single protein in", "single protein in humans", "in humans reviewed", "humans reviewed in", "reviewed in maraia and", "in maraia and lamichhane", "maraia and lamichhane 2011", "and lamichhane 2011 .", "lamichhane 2011 . elac2", "2011 . elac2 is", ". elac2 is a", "elac2 is a rnase", "is a rnase z", "a rnase z found", "rnase z found in", "z found in both", "found in both nucleus", "in both nucleus and", "both nucleus and mitochondria.", "nucleus and mitochondria. elac1", "and mitochondria. elac1 is", "mitochondria. elac1 is found", "elac1 is found in", "is found in the", "found in the cytosol", "in the cytosol and", "the cytosol and may", "cytosol and may also", "and may also act", "may also act as", "also act as an", "act as an rnase", "as an rnase z.", "an rnase z. human", "rnase z. human trna", "z. human trna genes", "human trna genes do", "trna genes do not", "genes do not encode", "do not encode the", "not encode the universal", "encode the universal acceptor", "the universal acceptor 3'", "universal acceptor 3' terminus", "acceptor 3' terminus cca", "terminus cca instead", "cca instead it", "instead it is added", "it is added post", "is added post transcriptionally", "added post transcriptionally by", "post transcriptionally by trnt1", "by trnt1 an", "trnt1 an unusual", "an unusual polymerase that", "unusual polymerase that requires", "polymerase that requires no", "that requires no nucleic", "requires no nucleic acid", "no nucleic acid template", "acid template reviewed", "template reviewed in", "reviewed in xiong and", "in xiong and steitz", "xiong and steitz 2006", "steitz 2006 hou", "2006 hou 2010", "hou 2010 tomita", "2010 tomita and", "tomita and yamashita 2014", "and yamashita 2014 .
in", "yamashita 2014 .
in humans", "2014 .
in humans introns", ".
in humans introns are", "humans introns are spliced", "introns are spliced from", "are spliced from intron", "spliced from intron containing", "from intron containing trnas", "intron containing trnas in", "containing trnas in the", "trnas in the nucleus", "the nucleus by a", "nucleus by a two", "by a two step", "a two step mechanism", "two step mechanism that", "step mechanism that is", "mechanism that is distinct", "that is distinct from", "is distinct from mrna", "distinct from mrna splicing", "mrna splicing reviewed", "splicing reviewed in", "reviewed in popow et", "in popow et al.", "popow et al. 2012", "al. 2012 lopes", "2012 lopes et", "lopes et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the tsen", ". the tsen complex", "the tsen complex first", "tsen complex first cleaves", "complex first cleaves 5'", "first cleaves 5' and", "cleaves 5' and 3'", "5' and 3' to", "and 3' to the", "3' to the intron", "the intron generating", "intron generating a", "generating a 2'3' cyclic", "a 2'3' cyclic phosphate", "2'3' cyclic phosphate on", "cyclic phosphate on the", "phosphate on the 5'", "on the 5' exon", "the 5' exon and", "5' exon and a", "exon and a 5'", "and a 5' hydroxyl", "a 5' hydroxyl group", "5' hydroxyl group on", "hydroxyl group on the", "group on the 3'", "on the 3' exon.", "the 3' exon. these", "3' exon. these two", "exon. these two ends", "these two ends are", "two ends are ligated", "ends are ligated by", "are ligated by a", "ligated by a complex", "by a complex containing", "a complex containing at", "complex containing at least", "containing at least 6", "at least 6 proteins", "least 6 proteins in", "6 proteins in a", "proteins in a single", "in a single reaction", "a single reaction that", "single reaction that both", "reaction that both hydrolyzes", "that both hydrolyzes the", "both hydrolyzes the 2'", "hydrolyzes the 2' phosphate", "the 2' phosphate bond", "2' phosphate bond and", "phosphate bond and joins", "bond and joins the", "and joins the 3'", "joins the 3' phosphate", "the 3' phosphate to", "3' phosphate to the", "phosphate to the 5'", "to the 5' hydroxyl.", "5' hydroxyl. in", "hydroxyl. in yeast", "in yeast the ligation", "yeast the ligation and", "the ligation and the", "ligation and the hydrolysis", "and the hydrolysis of", "the hydrolysis of the", "hydrolysis of the 2'", "of the 2' phosphate", "the 2' phosphate are", "2' phosphate are separate", "phosphate are separate reactions.", "are separate reactions. the", "separate reactions. the splicing", "reactions. the splicing reactions", "the splicing reactions in", "splicing reactions in yeast", "reactions in yeast occur", "in yeast occur in", "yeast occur in the", "occur in the cytosol", "in the cytosol at", "the cytosol at the", "cytosol at the mitochondrial", "at the mitochondrial outer", "the mitochondrial outer membrane.", "outer membrane.
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the", "and hopper 2010 .
the order", "hopper 2010 .
the order of", "2010 .
the order of processing", ".
the order of processing and", "order of processing and nucleotide", "of processing and nucleotide modification", "processing and nucleotide modification events", "and nucleotide modification events may", "nucleotide modification events may be", "modification events may be different", "events may be different for", "may be different for different", "be different for different trnas", "different for different trnas and", "for different trnas and its", "different trnas and its analysis", "trnas and its analysis is", "and its analysis is complicated", "its analysis is complicated by", "analysis is complicated by a", "is complicated by a retrograde", "complicated by a retrograde transport", "by a retrograde transport mechanism", "a retrograde transport mechanism that", "retrograde transport mechanism that can", "transport mechanism that can import", "mechanism that can import trnas", "that can import trnas from", "can import trnas from the", "import trnas from the cytosol", "trnas from the cytosol back", "from the cytosol back to", "the cytosol back to the", "cytosol back to the nucleus", "to the nucleus retrograde", "the nucleus retrograde movement", "retrograde movement shaheen and", "movement shaheen and hopper", "and hopper 2005 reviewed", "hopper 2005 reviewed in", "2005 reviewed in phizicky", "reviewed in phizicky 2005", "in phizicky 2005 .", "phizicky 2005 . generally", "2005 . generally the", ". generally the 5'", "generally the 5' leader", "the 5' leader of the", "5' leader of the pre", "leader of the pre trna", "of the pre trna is", "the pre trna is removed", "pre trna is removed first", "trna is removed first by", "is removed first by endonucleolytic", "removed first by endonucleolytic cleavage", "first by endonucleolytic cleavage by", "by endonucleolytic cleavage by the", "endonucleolytic cleavage by the rnase", "cleavage by the rnase p", "by the rnase p ribonucleoprotein", "the rnase p ribonucleoprotein complex", "p ribonucleoprotein complex which", "ribonucleoprotein complex which contains", "complex which contains a", "which contains a catalytic rna", "a catalytic rna rna", "catalytic rna rna h1", "rna rna h1 in", "h1 in humans and", "in humans and at", "humans and at least", "and at least 10 protein", "at least 10 protein subunits", "10 protein subunits reviewed", "protein subunits reviewed in", "subunits reviewed in jarrous", "in jarrous 2002 xiao", "jarrous 2002 xiao et", "2002 xiao et al.", "et al. 2002 jarrous", "al. 2002 jarrous and", "2002 jarrous and gopalan", "jarrous and gopalan 2010 .
the", "and gopalan 2010 .
the 3'", "gopalan 2010 .
the 3' trailer", "2010 .
the 3' trailer is", ".
the 3' trailer is then", "3' trailer is then removed", "trailer is then removed by", "is then removed by rnase", "then removed by rnase z", "removed by rnase z activity", "rnase z activity a", "z activity a single", "activity a single protein", "a single protein in humans", "protein in humans reviewed", "in humans reviewed in", "humans reviewed in maraia", "reviewed in maraia and lamichhane", "in maraia and lamichhane 2011", "maraia and lamichhane 2011 .", "and lamichhane 2011 . elac2", "lamichhane 2011 . elac2 is", "2011 . elac2 is a", ". elac2 is a rnase", "elac2 is a rnase z", "is a rnase z found", "a rnase z found in", "rnase z found in both", "z found in both nucleus", "found in both nucleus and", "in both nucleus and mitochondria.", "both nucleus and mitochondria. elac1", "nucleus and mitochondria. elac1 is", "and mitochondria. elac1 is found", "mitochondria. elac1 is found in", "elac1 is found in the", "is found in the cytosol", "found in the cytosol and", "in the cytosol and may", "the cytosol and may also", "cytosol and may also act", "and may also act as", "may also act as an", "also act as an rnase", "act as an rnase z.", "as an rnase z. human", "an rnase z. human trna", "rnase z. human trna genes", "z. human trna genes do", "human trna genes do not", "trna genes do not encode", "genes do not encode the", "do not encode the universal", "not encode the universal acceptor", "encode the universal acceptor 3'", "the universal acceptor 3' terminus", "universal acceptor 3' terminus cca", "3' terminus cca instead", "terminus cca instead it", "cca instead it is", "instead it is added post", "it is added post transcriptionally", "is added post transcriptionally by", "added post transcriptionally by trnt1", "transcriptionally by trnt1 an", "by trnt1 an unusual", "trnt1 an unusual polymerase", "an unusual polymerase that requires", "unusual polymerase that requires no", "polymerase that requires no nucleic", "that requires no nucleic acid", "requires no nucleic acid template", "nucleic acid template reviewed", "acid template reviewed in", "template reviewed in xiong", "reviewed in xiong and steitz", "in xiong and steitz 2006", "and steitz 2006 hou", "steitz 2006 hou 2010", "hou 2010 tomita and", "2010 tomita and yamashita", "tomita and yamashita 2014 .
in", "and yamashita 2014 .
in humans", "yamashita 2014 .
in humans introns", "2014 .
in humans introns are", ".
in humans introns are spliced", "humans introns are spliced from", "introns are spliced from intron", "are spliced from intron containing", "spliced from intron containing trnas", "from intron containing trnas in", "intron containing trnas in the", "containing trnas in the nucleus", "trnas in the nucleus by", "in the nucleus by a", "the nucleus by a two", "nucleus by a two step", "by a two step mechanism", "a two step mechanism that", "two step mechanism that is", "step mechanism that is distinct", "mechanism that is distinct from", "that is distinct from mrna", "is distinct from mrna splicing", "from mrna splicing reviewed", "mrna splicing reviewed in", "splicing reviewed in popow", "reviewed in popow et al.", "in popow et al. 2012", "et al. 2012 lopes", "al. 2012 lopes et", "2012 lopes et al.", "lopes et al. 2015 .", "et al. 2015 . the", "al. 2015 . the tsen", "2015 . the tsen complex", ". the tsen complex first", "the tsen complex first cleaves", "tsen complex first cleaves 5'", "complex first cleaves 5' and", "first cleaves 5' and 3'", "cleaves 5' and 3' to", "5' and 3' to the", "and 3' to the intron", "to the intron generating", "the intron generating a", "intron generating a 2'3'", "generating a 2'3' cyclic phosphate", "a 2'3' cyclic phosphate on", "2'3' cyclic phosphate on the", "cyclic phosphate on the 5'", "phosphate on the 5' exon", "on the 5' exon and", "the 5' exon and a", "5' exon and a 5'", "exon and a 5' hydroxyl", "and a 5' hydroxyl group", "a 5' hydroxyl group on", "5' hydroxyl group on the", "hydroxyl group on the 3'", "group on the 3' exon.", "on the 3' exon. these", "the 3' exon. these two", "3' exon. these two ends", "exon. these two ends are", "these two ends are ligated", "two ends are ligated by", "ends are ligated by a", "are ligated by a complex", "ligated by a complex containing", "by a complex containing at", "a complex containing at least", "complex containing at least 6", "containing at least 6 proteins", "at least 6 proteins in", "least 6 proteins in a", "6 proteins in a single", "proteins in a single reaction", "in a single reaction that", "a single reaction that both", "single reaction that both hydrolyzes", "reaction that both hydrolyzes the", "that both hydrolyzes the 2'", "both hydrolyzes the 2' phosphate", "hydrolyzes the 2' phosphate bond", "the 2' phosphate bond and", "2' phosphate bond and joins", "phosphate bond and joins the", "bond and joins the 3'", "and joins the 3' phosphate", "joins the 3' phosphate to", "the 3' phosphate to the", "3' phosphate to the 5'", "phosphate to the 5' hydroxyl.", "the 5' hydroxyl. in", "5' hydroxyl. in yeast", "hydroxyl. in yeast the", "in yeast the ligation and", "yeast the ligation and the", "the ligation and the hydrolysis", "ligation and the hydrolysis of", "and the hydrolysis of the", "the hydrolysis of the 2'", "hydrolysis of the 2' phosphate", "of the 2' phosphate are", "the 2' phosphate are separate", "2' phosphate are separate reactions.", "phosphate are separate reactions. the", "are separate reactions. the splicing", "separate reactions. the splicing reactions", "reactions. the splicing reactions in", "the splicing reactions in yeast", "splicing reactions in yeast occur", "reactions in yeast occur in", "in yeast occur in the", "yeast occur in the cytosol", "occur in the cytosol at", "in the cytosol at the", "the cytosol at the mitochondrial", "cytosol at the mitochondrial outer", "at the mitochondrial outer membrane.", "mitochondrial outer membrane.
mature", "outer membrane.
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may", "trna these reactions may occur", "these reactions may occur before", "reactions may occur before or", "may occur before or after", "occur before or after splicing", "before or after splicing and", "or after splicing and before", "after splicing and before or", "splicing and before or after", "and before or after export", "before or after export from", "or after export from the", "after export from the nucleus", "export from the nucleus to", "from the nucleus to the", "the nucleus to the cytosol." ] }, { "record_id": "GLY_000594_1_510", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6785470", "r hsa", "hsa 6785470", "r hsa 6785470" ] }, { "record_id": "GLY_000594_1_510", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "trna processing", "processing in", "in the", "the mitochondrion", "trna processing in", "processing in the", "in the mitochondrion", "trna processing in the", "processing 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al.", "in suzuki et al. 2011", "et al. 2011 rossmanith", "al. 2011 rossmanith 2012", "rossmanith 2012 powell et", "2012 powell et al.", "powell et al. 2015 .", "et al. 2015 . mitochondrial", "al. 2015 . mitochondrial rnase", "2015 . mitochondrial rnase p", "mitochondrial rnase p which", "rnase p which is", "p which is completely", "which is completely distinct from", "is completely distinct from nuclear", "completely distinct from nuclear rnase", "distinct from nuclear rnase p", "from nuclear rnase p in", "nuclear rnase p in having", "rnase p in having different", "p in having different protein", "in having different protein subunits", "having different protein subunits and", "different protein subunits and no", "protein subunits and no rna", "subunits and no rna component", "no rna component cleaves", "rna component cleaves at", "component cleaves at the", "cleaves at the 5' ends", "at the 5' ends of", "the 5' ends of trnas.", "5' ends of trnas. rnase", "ends of trnas. rnase z", "trnas. rnase z an", "rnase z an isoform", "z an isoform of", "an isoform of elac2 in", "isoform of elac2 in mitochondria", "elac2 in mitochondria cleaves", "in mitochondria cleaves at", "mitochondria cleaves at the", "cleaves at the 3' ends", "at the 3' ends of", "the 3' ends of trnas.", "ends of trnas. a", "of trnas. a different", "trnas. a different isoform", "a different isoform of elac2", "different isoform of elac2 serves", "isoform of elac2 serves as", "of elac2 serves as rnase", "elac2 serves as rnase z", "serves as rnase z in", "as rnase z in the", "rnase z in the nucleus.", "in the nucleus. unknown", "the nucleus. unknown nucleases", "nucleus. unknown nucleases make", "unknown nucleases make additional cleavages", "nucleases make additional cleavages near", "make additional cleavages near the", "additional cleavages near the 5'", "cleavages near the 5' end", "near the 5' end of", "the 5' end of mt", "5' end of mt co3", "of mt co3 the", "mt co3 the 5'", "co3 the 5' end", "the 5' end of co1", "end of co1 the", "of co1 the 5'", "co1 the 5' end", "the 5' end of cyb", "end of cyb and", "of cyb and the", "cyb and the 3'", "and the 3' end of", "the 3' end of nd6.", "3' end of nd6. trnt1", "of nd6. trnt1 cca", "nd6. trnt1 cca adding", "trnt1 cca adding enzyme", "cca adding enzyme then", "adding enzyme then post", "enzyme then post transcriptionally", "then post transcriptionally polymerizes the", "post transcriptionally polymerizes the universal", "transcriptionally polymerizes the universal acceptor", "polymerizes the universal acceptor sequence", "the universal acceptor sequence cca", "universal acceptor sequence cca onto", "acceptor sequence cca onto the", "sequence cca onto the 3'", "cca onto the 3' ends", "onto the 3' ends of", "the 3' ends of the", "3' ends of the cleaved", "ends of the cleaved trnas.", "of the cleaved trnas. in", "the cleaved trnas. in yeast", "trnas. in yeast plants", "yeast plants and", "plants and protozoa additional", "and protozoa additional trnas encoded", "protozoa additional trnas encoded in", "additional trnas encoded in the", "trnas encoded in the nucleus", "encoded in the nucleus are", "in the nucleus are imported", "the nucleus are imported into", "nucleus are imported into mitochondria", "are imported into mitochondria from", "imported into mitochondria from the", "into mitochondria from the cytosol", "from the cytosol reviewed", "the cytosol reviewed in", "cytosol reviewed in schneider", "schneider 2011 however", "2011 however human", "however human mitochondria encode a", "human mitochondria encode a complete", "mitochondria encode a complete complement", "encode a complete complement of", "a complete complement of 22", "complete complement of 22 trnas", "complement of 22 trnas required", "of 22 trnas required for", "22 trnas required for translation", "trnas required for translation and", "required for translation and trna", "for translation and trna import", "translation and trna import has", "and trna import has not", "trna import has not been", "import has not been observed", "has not been observed in", "not been observed in mammals.", "been observed in mammals. mutations", "observed in mammals. mutations that", "in mammals. mutations that affect", "mammals. mutations that affect mitochondrial", "mutations that affect mitochondrial trna", "that affect mitochondrial trna processing", "affect mitochondrial trna processing cause", "mitochondrial trna processing cause human", "trna processing cause human diseases", "processing cause human diseases that", "cause human diseases that are", "human diseases that are generally", "diseases that are generally characterized", "that are generally characterized by", "are generally characterized by abnormalities", "generally characterized by abnormalities in", "characterized by abnormalities in energy", "by abnormalities in energy requiring", "abnormalities in energy requiring tissues", "in energy requiring tissues such", "energy requiring tissues such as", "requiring tissues such as brain", "tissues such as brain and", "such as brain and muscle", "brain and muscle reviewed", "and muscle reviewed in", "muscle reviewed in suzuki", "et al. 2011 sarin", "al. 2011 sarin and", "2011 sarin and leidel", "sarin and leidel 2014 ." ] }, { "record_id": "GLY_000594_1_511", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6785631", "r hsa", "hsa 6785631", "r hsa 6785631" ] }, { "record_id": "GLY_000594_1_511", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "erbb2 regulates", "regulates cell", "cell motility", "erbb2 regulates cell", "regulates cell motility", "erbb2 regulates cell motility", "activated erbb2", "erbb2 heterodimers", "heterodimers regulate", "regulate cell", "motility through", "through association", "association with", "with memo1.", "memo1. memo1", "memo1 retains", "retains activated", "activated rhoa", "rhoa gtpase", "gtpase 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interleukin 13", "4 and interleukin 13 signaling", "is a", "a principal", "principal regulatory", "regulatory cytokine", "cytokine during", "during the", "the immune", "immune response", "crucially important", "important in", "in allergy", "allergy and", "and asthma", "nelms et", "et al.", "al. 1999", "1999 .", ". when", "when resting", "resting t", "t cells", "cells are", "are antigen", "antigen activated", "activated and", "and expand", "expand in", "in response", "response to", "to interleukin", "interleukin 2", "they can", "can differentiate", "differentiate as", "as type", "type 1", "or type", "type 2", "t helper", "helper cells.", "cells. the", "the outcome", "outcome is", "is influenced", "influenced by", "by il4.", "il4. th2", "th2 cells", "cells secrete", "secrete il4", "which both", "both stimulates", "stimulates th2", "th2 in", "in an", "an autocrine", "autocrine fashion", "fashion and", "and acts", "acts as", "as a", "a potent", "potent b", "b cell", "cell growth", "growth factor", "factor to", "to promote", "promote humoral", "humoral immunity", ".

interleukin", "

interleukin 13", "is an", "an immunoregulatory", "immunoregulatory cytokine", "cytokine secreted", "secreted predominantly", "predominantly by", "by activated", "activated th2", "th2 cells.", "cells. it", "it is", "a key", "key mediator", "mediator in", "in the", "the pathogenesis", "pathogenesis of", "of allergic", "allergic inflammation.", "inflammation. il13", "il13 shares", "shares many", "many functional", "functional properties", "properties with", "with il4", "stemming from", "from the", "the fact", "fact that", "that they", "they share", "share a", "a common", "common receptor", "receptor subunit.", "subunit. il13", "il13 receptors", "receptors are", "are expressed", "expressed on", "on human", "human b", "b cells", "mast cells", "endothelial cells", "respiratory epithelial", "epithelial cells", "and smooth", "smooth muscle", "muscle cells", "but unlike", "unlike il4", "not t", "t cells.", "cells. thus", "thus il13", "il13 does", "does not", "not appear", "appear to", "to be", "be important", "the initial", "initial differentiation", "differentiation of", "of cd4", "cd4 t", "cells into", "into th2", "rather it", "is important", "the effector", "effector phase", "phase of", "allergic inflammation", "hershey et", "al. 2003", "2003 .", ". il4", "il4 and", "and il13", "il13 induce", "induce \u201calternative", "\u201calternative activation\u201d", "activation\u201d of", "of macrophages", "inducing an", "an anti", "anti inflammatory", "inflammatory phenotype", "phenotype by", "by signaling", "signaling through", "through il4r", "il4r alpha", "alpha in", "in a", "a stat6", "stat6 dependent", "dependent manner.", "manner. this", "this signaling", "signaling plays", "plays an", "an important", "important role", "role in", "the th2", "th2 response", "mediating anti", "anti parasitic", "parasitic effects", "effects and", "and aiding", "aiding wound", "wound healing", "gordon &", "& martinez", "martinez 2010", "loke et", "al. 2002", "there are", "are two", "two types", "types of", "of il4", "il4 receptor", "receptor complex", "andrews et", "al. 2006", "2006 .", ". type", "type i", "i il4r", "is predominantly", "predominantly expressed", "on the", "the surface", "surface of", "of hematopoietic", "hematopoietic cells", "cells and", "and consists", "consists of", "of il4r", "il4r and", "and il2rg", "the common", "common gamma", "gamma chain.", "chain. type", "type ii", "ii il4r", "of nonhematopoietic", "nonhematopoietic cells", "it consists", "and il13ra1", "il13ra1 and", "and is", "is also", "also the", "the type", "ii receptor", "receptor for", "for il13.", "obiri et", "al. 1995", "aman et", "al. 1996", "hilton et", "miloux et", "al. 1997", "zhang et", "1997 .", ". the", "the second", "second receptor", "for il13", "il13 consists", "13 receptor", "receptor alpha", "alpha 2", "sometimes called", "called interleukin", "13 binding", "binding protein", "il13bp .", ". it", "it has", "has a", "a high", "high affinity", "affinity receptor", "kd =", "= 250", "250 pmol/l", "but is", "is not", "not sufficient", "sufficient to", "to render", "render cells", "cells responsive", "responsive to", "to il13", "even in", "the presence", "presence of", "donaldson et", "al. 1998", "1998 .", "is reported", "reported to", "to exist", "exist in", "in soluble", "soluble form", "and when", "when overexpressed", "overexpressed reduces", "reduces jak", "jak stat", "stat signaling", "kawakami et", "al. 2001", "2001 .", ". it's", "it's function", "function may", "may be", "be to", "to prevent", "prevent il13", "il13 signalling", "signalling via", "via the", "the functional", "functional il4r:il13ra1", "il4r:il13ra1 receptor.", "receptor. il13ra2", "il13ra2 is", "is overexpressed", "overexpressed and", "and enhances", "enhances cell", "cell invasion", "invasion in", "in some", "some human", "human cancers", "joshi &", "& puri", "puri 2012", "2012 .

the", ".

the first", "first step", "step in", "the formation", "formation of", "of il4r1", "is the", "the binding", "binding of", "il4 with", "with il4r", "hoffman et", "shen et", "hage et", ". this", "this is", "the first", "in formation", "of il4r2", "il4:il4r:il13ra1 .", ". after", "after the", "initial binding", "and il4r", "il2rb binds", "laporte et", "al. 2008", "to form", "form il4r1.", "il4r1. alternatively", "il13ra1 binds", "forming il4r2.", "il4r2. in", "in contrast", "ii il13", "il13 complex", "forms with", "with il13", "il13 first", "first binding", "binding to", "to il13ra1", "il13ra1 followed", "followed by", "by recruitment", "recruitment of", "wang et", "al. 2009", "2009 .

crystal", ".

crystal structures", "structures of", "of the", "the il4:il4r:il2rg", "il4:il4r:il13ra1 and", "and il13:il4r:il13ra1", "il13:il4r:il13ra1 complexes", "complexes have", "have been", "been determined", "2008 .", ". consistent", "consistent with", "with these", "these structures", "in monocytes", "monocytes il4r", "il4r is", "is tyrosine", "tyrosine phosphorylated", "phosphorylated in", "to both", "both il4", "roy et", "while il13ra1", "il13ra1 phosphorylation", "phosphorylation is", "is induced", "induced only", "only by", "by il13", "il2rg phosphorylation", "by il4", "2002 .

both", ".

both il4", "receptor complexes", "complexes signal", "signal through", "through jak/stat", "jak/stat cascades.", "cascades. il4r", "is constitutively", "constitutively associated", "associated with", "with jak2", "and associates", "associates with", "with jak1", "jak1 following", "following binding", "yin et", "al. 1994", "or il13", "2002 .", ". il2rg", "il2rg constitutively", "constitutively associates", "with jak3", "boussiotis et", "1994 .", ". il13ra1", "il13ra1 constitutively", "with tyk2", "umeshita suyama", "suyama et", "al. 2000", "bhattacharjee et", "al. 2013", "2013 .", ".

il4", "

il4 binding", "to il4r1", "il4r1 leads", "leads to", "to phosphorylation", "phosphorylation of", "of jak1", "but not", "not jak2", "and stat6", "stat6 activation", "takeda et", "ratthe et", "al. 2007", ".

il13", "

il13 binding", "binding increases", "increases activating", "activating tyrosine", "tyrosine 99", "99 phosphorylation", "of il13ra1", "il13ra1 but", "not that", "that of", "of il2rg.", "il2rg. il4", "il4 binding", "to il2rg", "il2rg leads", "to its", "its tyrosine", "tyrosine phosphorylation", ". il13", "il13 binding", "to il4r2", "il4r2 leads", "to tyk2", "tyk2 and", "and jak2", "not jak1", "roy &", "& cathcart", "cathcart 1998", "2002 .

phosphorylated", ".

phosphorylated tyk2", "tyk2 binds", "binds and", "and phosphorylates", "phosphorylates stat6", "stat6 and", "and possibly", "possibly stat1", "

a second", "second mechanism", "mechanism of", "of signal", "signal transduction", "transduction activated", "activated by", "il13 leads", "to the", "the insulin", "insulin receptor", "receptor substrate", "kelly welch", "welch et", ". il4r1", "il4r1 associates", "with insulin", "substrate 2", "2 and", "and activates", "activates the", "the pi3k/akt", "pi3k/akt and", "and ras/mek/erk", "ras/mek/erk pathways", "pathways involved", "involved in", "in cell", "cell proliferation", "survival and", "and translational", "translational control.", "control. il4r2", "il4r2 does", "not associate", "associate with", "and consequently", "consequently the", "pathways are", "are not", "not activated", "busch dienstfertig", "dienstfertig &", "& gonz\u00e1lez", "gonz\u00e1lez rodr\u00edguez", "rodr\u00edguez 2013", "4 il4", "il4 is", "is a principal", "a principal regulatory", "principal regulatory cytokine", "regulatory cytokine during", "cytokine during the", "during the immune", "the immune response", "response crucially", "crucially important in", "important in allergy", "in allergy and", "allergy and asthma", "asthma nelms", "nelms et al.", "et al. 1999", "al. 1999 .", "1999 . when", ". when resting", "when resting t", "resting t cells", "t cells are", "cells are antigen", "are antigen activated", "antigen activated and", "activated and expand", "and expand in", "expand in response", "in response to", "response to interleukin", "to interleukin 2", "2 il2", "they can differentiate", "can differentiate as", "differentiate as type", "as type 1", "1 th1", "th1 or", "or type 2", "2 th2", "th2 t", "t helper cells.", "helper cells. the", "cells. the outcome", "the outcome is", "outcome is influenced", "is influenced by", "influenced by il4.", "by il4. th2", "il4. th2 cells", "th2 cells secrete", "cells secrete il4", "il4 which", "which both stimulates", "both stimulates th2", "stimulates th2 in", "th2 in an", "in an autocrine", "an autocrine fashion", "autocrine fashion and", "fashion and acts", "and acts as", "acts as a", "as a potent", "a potent b", "potent b cell", "b cell growth", "cell growth factor", "growth factor to", "factor to promote", "to promote humoral", "promote humoral immunity", "immunity nelms", "1999 .

interleukin", ".

interleukin 13", "13 il13", "il13 is", "is an immunoregulatory", "an immunoregulatory cytokine", "immunoregulatory cytokine secreted", "cytokine secreted predominantly", "secreted predominantly by", "predominantly by activated", "by activated th2", "activated th2 cells.", "th2 cells. it", "cells. it is", "it is a", "is a key", "a key mediator", "key mediator in", "mediator in the", "in the pathogenesis", "the pathogenesis of", "pathogenesis of allergic", "of allergic inflammation.", "allergic inflammation. il13", "inflammation. il13 shares", "il13 shares many", "shares many functional", "many functional properties", "functional properties with", "properties with il4", "il4 stemming", "stemming from the", "from the fact", "the fact that", "fact that they", "that they share", "they share a", "share a common", "a common receptor", "common receptor subunit.", "receptor subunit. il13", "subunit. il13 receptors", "il13 receptors are", "receptors are expressed", "are expressed on", "expressed on human", "on human b", "human b cells", "cells basophils", "basophils eosinophils", "eosinophils mast", "cells endothelial", "cells fibroblasts", "fibroblasts monocytes", "monocytes macrophages", "macrophages respiratory", "respiratory epithelial cells", "and smooth muscle", "smooth muscle cells", "cells but", "but unlike il4", "il4 not", "not t cells.", "t cells. thus", "cells. thus il13", "thus il13 does", "il13 does not", "does not appear", "not appear to", "appear to be", "to be important", "be important in", "important in the", "in the initial", "the initial differentiation", "initial differentiation of", "differentiation of cd4", "of cd4 t", "cd4 t cells", "t cells into", "cells into th2", "into th2 cells", "cells rather", "rather it is", "it is important", "is important in", "in the effector", "the effector phase", "effector phase of", "phase of allergic", "of allergic inflammation", "inflammation hershey", "hershey et al.", "et al. 2003", "al. 2003 .", "2003 . il4", ". il4 and", "il4 and il13", "and il13 induce", "il13 induce \u201calternative", "induce \u201calternative activation\u201d", "\u201calternative activation\u201d of", "activation\u201d of macrophages", "macrophages inducing", "inducing an anti", "an anti inflammatory", "anti inflammatory phenotype", "inflammatory phenotype by", "phenotype by signaling", "by signaling through", "signaling through il4r", "through il4r alpha", "il4r alpha in", "alpha in a", "in a stat6", "a stat6 dependent", "stat6 dependent manner.", "dependent manner. this", "manner. this signaling", "this signaling plays", "signaling plays an", "plays an important", "an important role", "important role in", "role in the", "in the th2", "the th2 response", "response mediating", "mediating anti parasitic", "anti parasitic effects", "parasitic effects and", "effects and aiding", "and aiding wound", "aiding wound healing", "healing gordon", "gordon & martinez", "& martinez 2010", "2010 loke", "loke et al.", "et al. 2002", "2002 there", "there are two", "are two types", "two types of", "types of il4", "of il4 receptor", "il4 receptor complex", "complex andrews", "andrews et al.", "et al. 2006", "al. 2006 .", "2006 . type", ". type i", "type i il4r", "il4r il4r1", "il4r1 is", "is predominantly expressed", "predominantly expressed on", "expressed on the", "on the surface", "the surface of", "surface of hematopoietic", "of hematopoietic cells", "hematopoietic cells and", "cells and consists", "and consists of", "consists of il4r", "of il4r and", "il4r and il2rg", "il2rg the", "the common gamma", "common gamma chain.", "gamma chain. type", "chain. type ii", "type ii il4r", "il4r il4r2", "il4r2 is", "surface of nonhematopoietic", "of nonhematopoietic cells", "cells it", "it consists of", "il4r and il13ra1", "and il13ra1 and", "il13ra1 and is", "and is also", "is also the", "also the type", "the type ii", "type ii receptor", "ii receptor for", "receptor for il13.", "il13. obiri", "obiri et al.", "et al. 1995", "1995 aman", "aman et al.", "et al. 1996", "1996 hilton", "hilton et al.", "1996 miloux", "miloux et al.", "et al. 1997", "1997 zhang", "zhang et al.", "al. 1997 .", "1997 . the", ". the second", "the second receptor", "second receptor for", "receptor for il13", "for il13 consists", "il13 consists of", "il4r and interleukin", "interleukin 13 receptor", "13 receptor alpha", "receptor alpha 2", "2 il13ra2", "sometimes called interleukin", "called interleukin 13", "interleukin 13 binding", "13 binding protein", "protein il13bp", "il13bp . it", ". it has", "it has a", "has a high", "a high affinity", "high affinity receptor", "affinity receptor for", "il13 kd", "kd = 250", "= 250 pmol/l", "pmol/l but", "but is not", "is not sufficient", "not sufficient to", "sufficient to render", "to render cells", "render cells responsive", "cells responsive to", "responsive to il13", "il13 even", "even in the", "in the presence", "the presence of", "presence of il4r", "il4r donaldson", "donaldson et al.", "et al. 1998", "al. 1998 .", "1998 . it", ". it is", "it is reported", "is reported to", "reported to exist", "to exist in", "exist in soluble", "in soluble form", "form zhang", "1997 and", "and when overexpressed", "when overexpressed reduces", "overexpressed reduces jak", "reduces jak stat", "jak stat signaling", "signaling kawakami", "kawakami et al.", "et al. 2001", "al. 2001 .", "2001 . it's", ". it's function", "it's function may", "function may be", "may be to", "be to prevent", "to prevent il13", "prevent il13 signalling", "il13 signalling via", "signalling via the", "via the functional", "the functional il4r:il13ra1", "functional il4r:il13ra1 receptor.", "il4r:il13ra1 receptor. il13ra2", "receptor. il13ra2 is", "il13ra2 is overexpressed", "is overexpressed and", "overexpressed and enhances", "and enhances cell", "enhances cell invasion", "cell invasion in", "invasion in some", "in some human", "some human cancers", "cancers joshi", "joshi & puri", "& puri 2012", "puri 2012 .

the", "2012 .

the first", ".

the first step", "first step in", "step in the", "in the formation", "the formation of", "formation of il4r1", "il4r1 il4:il4r:il2rb", "il4:il4r:il2rb is", "is the binding", "the binding of", "binding of il4", "of il4 with", "il4 with il4r", "il4r hoffman", "hoffman et al.", "1995 shen", "shen et al.", "1996 hage", "hage et al.", "1999 . this", ". this is", "this is also", "also the first", "the first step", "step in formation", "in formation of", "formation of il4r2", "il4r2 il4:il4r:il13ra1", "il4:il4r:il13ra1 . after", ". after the", "after the initial", "the initial binding", "initial binding of", "of il4 and", "il4 and il4r", "il4r il2rb", "binds laporte", "laporte et al.", "et al. 2008", "to form il4r1.", "form il4r1. alternatively", "alternatively il13ra1", "binds forming", "forming il4r2. in", "il4r2. in contrast", "contrast the", "type ii il13", "ii il13 complex", "complex il13r2", "il13r2 forms", "forms with il13", "with il13 first", "il13 first binding", "first binding to", "binding to il13ra1", "to il13ra1 followed", "il13ra1 followed by", "followed by recruitment", "by recruitment of", "il4r wang", "wang et al.", "et al. 2009", "al. 2009 .

crystal", "2009 .

crystal structures", ".

crystal structures of", "structures of the", "of the il4:il4r:il2rg", "il4:il4r:il2rg il4:il4r:il13ra1", "il4:il4r:il13ra1 and il13:il4r:il13ra1", "and il13:il4r:il13ra1 complexes", "il13:il4r:il13ra1 complexes have", "complexes have been", "have been determined", "determined laporte", "al. 2008 .", "2008 . consistent", ". consistent with", "consistent with these", "with these structures", "structures in", "in monocytes il4r", "monocytes il4r is", "il4r is tyrosine", "is tyrosine phosphorylated", "tyrosine phosphorylated in", "phosphorylated in response", "response to both", "to both il4", "both il4 and", "il13 roy", "roy et al.", "2002 gordon", "2010 while", "while il13ra1 phosphorylation", "il13ra1 phosphorylation is", "phosphorylation is induced", "is induced only", "induced only by", "only by il13", "2002 laporte", "2008 and", "and il2rg phosphorylation", "il2rg phosphorylation is", "only by il4", "il4 roy", "al. 2002 .

both", "2002 .

both il4", ".

both il4 receptor", "il4 receptor complexes", "receptor complexes signal", "complexes signal through", "signal through jak/stat", "through jak/stat cascades.", "jak/stat cascades. il4r", "cascades. il4r is", "il4r is constitutively", "is constitutively associated", "constitutively associated with", "associated with jak2", "jak2 roy", "2002 and", "and associates with", "associates with jak1", "with jak1 following", "jak1 following binding", "following binding of", "il4 yin", "yin et al.", "et al. 1994", "1994 or", "al. 2002 .", "2002 . il2rg", ". il2rg constitutively", "il2rg constitutively associates", "constitutively associates with", "associates with jak3", "jak3 boussiotis", "boussiotis et al.", "1994 russell", "russell et", "al. 1994 .", "1994 . il13ra1", ". il13ra1 constitutively", "il13ra1 constitutively associates", "associates with tyk2", "tyk2 umeshita", "umeshita suyama et", "suyama et al.", "et al. 2000", "2000 roy", "2008 bhattacharjee", "bhattacharjee et al.", "et al. 2013", "al. 2013 .", "2013 .

il4", ".

il4 binding", "

il4 binding to", "binding to il4r1", "to il4r1 leads", "il4r1 leads to", "leads to phosphorylation", "to phosphorylation of", "phosphorylation of jak1", "jak1 but", "but not jak2", "jak2 and", "and stat6 activation", "activation takeda", "takeda et al.", "1994 ratthe", "ratthe et al.", "et al. 2007", "2007 bhattacharjee", "2013 .

il13", ".

il13 binding", "

il13 binding increases", "binding increases activating", "increases activating tyrosine", "activating tyrosine 99", "tyrosine 99 phosphorylation", "99 phosphorylation of", "phosphorylation of il13ra1", "of il13ra1 but", "il13ra1 but not", "but not that", "not that of", "that of il2rg.", "of il2rg. il4", "il2rg. il4 binding", "il4 binding to", "binding to il2rg", "to il2rg leads", "il2rg leads to", "leads to its", "to its tyrosine", "its tyrosine phosphorylation", "phosphorylation roy", "2002 . il13", ". il13 binding", "il13 binding to", "binding to il4r2", "to il4r2 leads", "il4r2 leads to", "leads to tyk2", "to tyk2 and", "tyk2 and jak2", "jak2 but", "but not jak1", "jak1 phosphorylation", "roy & cathcart", "& cathcart 1998", "1998 roy", "al. 2002 .

phosphorylated", "2002 .

phosphorylated tyk2", ".

phosphorylated tyk2 binds", "tyk2 binds and", "binds and phosphorylates", "and phosphorylates stat6", "phosphorylates stat6 and", "stat6 and possibly", "and possibly stat1", "stat1 bhattacharjee", ".

a", "

a second mechanism", "second mechanism of", "mechanism of signal", "of signal transduction", "signal transduction activated", "transduction activated by", "activated by il4", "by il4 and", "and il13 leads", "il13 leads to", "leads to the", "to the insulin", "the insulin receptor", "insulin receptor substrate", "substrate irs", "irs family", "family kelly", "kelly welch et", "welch et al.", "2003 . il4r1", ". il4r1 associates", "il4r1 associates with", "associates with insulin", "with insulin receptor", "receptor substrate 2", "substrate 2 and", "2 and activates", "and activates the", "activates the pi3k/akt", "the pi3k/akt and", "pi3k/akt and ras/mek/erk", "and ras/mek/erk pathways", "ras/mek/erk pathways involved", "pathways involved in", "involved in cell", "in cell proliferation", "proliferation survival", "survival and translational", "and translational control.", "translational control. il4r2", "control. il4r2 does", "il4r2 does not", "does not associate", "not associate with", "associate with insulin", "2 and consequently", "and consequently the", "consequently the pi3k/akt", "ras/mek/erk pathways are", "pathways are not", "are not activated", "activated busch", "busch dienstfertig &", "dienstfertig & gonz\u00e1lez", "& gonz\u00e1lez rodr\u00edguez", "gonz\u00e1lez rodr\u00edguez 2013", "rodr\u00edguez 2013 .", "interleukin 4 il4", "il4 is a", "is a principal regulatory", "a principal regulatory cytokine", "principal regulatory cytokine during", "regulatory cytokine during the", "cytokine during the immune", "during the immune response", "immune response crucially", "response crucially important", "crucially important in allergy", "important in allergy and", "in allergy and asthma", "and asthma nelms", "asthma nelms et", "nelms et al. 1999", "et al. 1999 .", "al. 1999 . when", "1999 . when resting", ". when resting t", "when resting t cells", "resting t cells are", "t cells are antigen", "cells are antigen activated", "are antigen activated and", "antigen activated and expand", "activated and expand in", "and expand in response", "expand in response to", "in response to interleukin", "response to interleukin 2", "interleukin 2 il2", "il2 they", "they can differentiate as", "can differentiate as type", "differentiate as type 1", "type 1 th1", "th1 or type", "type 2 th2", "th2 t helper", "t helper cells. the", "helper cells. the outcome", "cells. the outcome is", "the outcome is influenced", "outcome is influenced by", "is influenced by il4.", "influenced by il4. th2", "by il4. th2 cells", "il4. th2 cells secrete", "th2 cells secrete il4", "secrete il4 which", "il4 which both", "which both stimulates th2", "both stimulates th2 in", "stimulates th2 in an", "th2 in an autocrine", "in an autocrine fashion", "an autocrine fashion and", "autocrine fashion and acts", "fashion and acts as", "and acts as a", "acts as a potent", "as a potent b", "a potent b cell", "potent b cell growth", "b cell growth factor", "cell growth factor to", "growth factor to promote", "factor to promote humoral", "to promote humoral immunity", "humoral immunity nelms", "immunity nelms et", "al. 1999 .

interleukin", "1999 .

interleukin 13", "

interleukin 13 il13", "il13 is an", "is an immunoregulatory cytokine", "an immunoregulatory cytokine secreted", "immunoregulatory cytokine secreted predominantly", "cytokine secreted predominantly by", "secreted predominantly by activated", "predominantly by activated th2", "by activated th2 cells.", "activated th2 cells. it", "th2 cells. it is", "cells. it is a", "it is a key", "is a key mediator", "a key mediator in", "key mediator in the", "mediator in the pathogenesis", "in the pathogenesis of", "the pathogenesis of allergic", "pathogenesis of allergic inflammation.", "of allergic inflammation. il13", "allergic inflammation. il13 shares", "inflammation. il13 shares many", "il13 shares many functional", "shares many functional properties", "many functional properties with", "functional properties with il4", "with il4 stemming", "il4 stemming from", "stemming from the fact", "from the fact that", "the fact that they", "fact that they share", "that they share a", "they share a common", "share a common receptor", "a common receptor subunit.", "common receptor subunit. il13", "receptor subunit. il13 receptors", "subunit. il13 receptors are", "il13 receptors are expressed", "receptors are expressed on", "are expressed on human", "expressed on human b", "on human b cells", "b cells basophils", "eosinophils mast cells", "mast cells endothelial", "cells endothelial cells", "endothelial cells fibroblasts", "macrophages respiratory epithelial", "epithelial cells and", "cells and smooth", "and smooth muscle cells", "muscle cells but", "cells but unlike", "unlike il4 not", "il4 not t", "not t cells. thus", "t cells. thus il13", "cells. thus il13 does", "thus il13 does not", "il13 does not appear", "does not appear to", "not appear to be", "appear to be important", "to be important in", "be important in the", "important in the initial", "in the initial differentiation", "the initial differentiation of", "initial differentiation of cd4", "differentiation of cd4 t", "of cd4 t cells", "cd4 t cells into", "t cells into th2", "cells into th2 cells", "th2 cells rather", "cells rather it", "rather it is important", "it is important in", "is important in the", "important in the effector", "in the effector phase", "the effector phase of", "effector phase of allergic", "phase of allergic inflammation", "allergic inflammation hershey", "inflammation hershey et", "hershey et al. 2003", "et al. 2003 .", "al. 2003 . il4", "2003 . il4 and", ". il4 and il13", "il4 and il13 induce", "and il13 induce \u201calternative", "il13 induce \u201calternative activation\u201d", "induce \u201calternative activation\u201d of", "\u201calternative activation\u201d of macrophages", "of macrophages inducing", "macrophages inducing an", "inducing an anti inflammatory", "an anti inflammatory phenotype", "anti inflammatory phenotype by", "inflammatory phenotype by signaling", "phenotype by signaling through", "by signaling through il4r", "signaling through il4r alpha", "through il4r alpha in", "il4r alpha in a", "alpha in a stat6", "in a stat6 dependent", "a stat6 dependent manner.", "stat6 dependent manner. this", "dependent manner. this signaling", "manner. this signaling plays", "this signaling plays an", "signaling plays an important", "plays an important role", "an important role in", "important role in the", "role in the th2", "in the th2 response", "th2 response mediating", "response mediating anti", "mediating anti parasitic effects", "anti parasitic effects and", "parasitic effects and aiding", "effects and aiding wound", "and aiding wound healing", "wound healing gordon", "healing gordon &", "gordon & martinez 2010", "martinez 2010 loke", "2010 loke et", "loke et al. 2002", "al. 2002 there", "2002 there are", "there are two types", "are two types of", "two types of il4", "types of il4 receptor", "of il4 receptor complex", "receptor complex andrews", "complex andrews et", "andrews et al. 2006", "et al. 2006 .", "al. 2006 . type", "2006 . type i", ". type i il4r", "i il4r il4r1", "il4r1 is predominantly", "is predominantly expressed on", "predominantly expressed on the", "expressed on the surface", "on the surface of", "the surface of hematopoietic", "surface of hematopoietic cells", "of hematopoietic cells and", "hematopoietic cells and consists", "cells and consists of", "and consists of il4r", "consists of il4r and", "of il4r and il2rg", "and il2rg the", "il2rg the common", "the common gamma chain.", "common gamma chain. type", "gamma chain. type ii", "chain. type ii il4r", "ii il4r il4r2", "il4r2 is predominantly", "the surface of nonhematopoietic", "surface of nonhematopoietic cells", "nonhematopoietic cells it", "cells it consists", "it consists of il4r", "of il4r and il13ra1", "il4r and il13ra1 and", "and il13ra1 and is", "il13ra1 and is also", "and is also the", "is also the type", "also the type ii", "the type ii receptor", "type ii receptor for", "ii receptor for il13.", "for il13. obiri", "il13. obiri et", "obiri et al. 1995", "al. 1995 aman", "1995 aman et", "aman et al. 1996", "al. 1996 hilton", "1996 hilton et", "hilton et al. 1996", "al. 1996 miloux", "1996 miloux et", "miloux et al. 1997", "al. 1997 zhang", "1997 zhang et", "zhang et al. 1997", "et al. 1997 .", "al. 1997 . the", "1997 . the second", ". the second receptor", "the second receptor for", "second receptor for il13", "receptor for il13 consists", "for il13 consists of", "il13 consists of il4r", "of il4r and interleukin", "il4r and interleukin 13", "and interleukin 13 receptor", "interleukin 13 receptor alpha", "13 receptor alpha 2", "alpha 2 il13ra2", "il13ra2 sometimes", "sometimes called interleukin 13", "called interleukin 13 binding", "interleukin 13 binding protein", "binding protein il13bp", "protein il13bp .", "il13bp . it has", ". it has a", "it has a high", "has a high affinity", "a high affinity receptor", "high affinity receptor for", "affinity receptor for il13", "for il13 kd", "il13 kd =", "kd = 250 pmol/l", "250 pmol/l but", "pmol/l but is", "but is not sufficient", "is not sufficient to", "not sufficient to render", "sufficient to render cells", "to render cells responsive", "render cells responsive to", "cells responsive to il13", "to il13 even", "il13 even in", "even in the presence", "in the presence of", "the presence of il4r", "of il4r donaldson", "il4r donaldson et", "donaldson et al. 1998", "et al. 1998 .", "al. 1998 . it", "1998 . it is", ". it is reported", "it is reported to", "is reported to exist", "reported to exist in", "to exist in soluble", "exist in soluble form", "soluble form zhang", "form zhang et", "al. 1997 and", "1997 and when", "and when overexpressed reduces", "when overexpressed reduces jak", "overexpressed reduces jak stat", "reduces jak stat signaling", "stat signaling kawakami", "signaling kawakami et", "kawakami et al. 2001", "et al. 2001 .", "al. 2001 . it's", "2001 . it's function", ". it's function may", "it's function may be", "function may be to", "may be to prevent", "be to prevent il13", "to prevent il13 signalling", "prevent il13 signalling via", "il13 signalling via the", "signalling via the functional", "via the functional il4r:il13ra1", "the functional il4r:il13ra1 receptor.", "functional il4r:il13ra1 receptor. il13ra2", "il4r:il13ra1 receptor. il13ra2 is", "receptor. il13ra2 is overexpressed", "il13ra2 is overexpressed and", "is overexpressed and enhances", "overexpressed and enhances cell", "and enhances cell invasion", "enhances cell invasion in", "cell invasion in some", "invasion in some human", "in some human cancers", "human cancers joshi", "cancers joshi &", "joshi & puri 2012", "& puri 2012 .

the", "puri 2012 .

the first", "2012 .

the first step", ".

the first step in", "first step in the", "step in the formation", "in the formation of", "the formation of il4r1", "of il4r1 il4:il4r:il2rb", "il4:il4r:il2rb is the", "is the binding of", "the binding of il4", "binding of il4 with", "of il4 with il4r", "with il4r hoffman", "il4r hoffman et", "hoffman et al. 1995", "al. 1995 shen", "1995 shen et", "shen et al. 1996", "al. 1996 hage", "1996 hage et", "hage et al. 1999", "al. 1999 . this", "1999 . this is", ". this is also", "this is also the", "is also the first", "also the first step", "the first step in", "first step in formation", "step in formation of", "in formation of il4r2", "of il4r2 il4:il4r:il13ra1", "il4r2 il4:il4r:il13ra1 .", "il4:il4r:il13ra1 . after the", ". after the initial", "after the initial binding", "the initial binding of", "initial binding of il4", "binding of il4 and", "of il4 and il4r", "and il4r il2rb", "il4r il2rb binds", "il2rb binds laporte", "binds laporte et", "laporte et al. 2008", "2008 to", "to form il4r1. alternatively", "il4r1. alternatively il13ra1", "alternatively il13ra1 binds", "il13ra1 binds forming", "binds forming il4r2.", "forming il4r2. in contrast", "in contrast the", "contrast the type", "the type ii il13", "type ii il13 complex", "il13 complex il13r2", "il13r2 forms with", "forms with il13 first", "with il13 first binding", "il13 first binding to", "first binding to il13ra1", "binding to il13ra1 followed", "to il13ra1 followed by", "il13ra1 followed by recruitment", "followed by recruitment of", "recruitment of il4r", "il4r wang et", "wang et al. 2009", "et al. 2009 .

crystal", "al. 2009 .

crystal structures", "2009 .

crystal structures of", ".

crystal structures of the", "structures of the il4:il4r:il2rg", "the il4:il4r:il2rg il4:il4r:il13ra1", "il4:il4r:il2rg il4:il4r:il13ra1 and", "il4:il4r:il13ra1 and il13:il4r:il13ra1 complexes", "and il13:il4r:il13ra1 complexes have", "il13:il4r:il13ra1 complexes have been", "complexes have been determined", "been determined laporte", "determined laporte et", "et al. 2008 .", "al. 2008 . consistent", "2008 . consistent with", ". consistent with these", "consistent with these structures", "these structures in", "structures in monocytes", "in monocytes il4r is", "monocytes il4r is tyrosine", "il4r is tyrosine phosphorylated", "is tyrosine phosphorylated in", "tyrosine phosphorylated in response", "phosphorylated in response to", "in response to both", "response to both il4", "to both il4 and", "both il4 and il13", "and il13 roy", "il13 roy et", "roy et al. 2002", "al. 2002 gordon", "2002 gordon &", "martinez 2010 while", "2010 while il13ra1", "while il13ra1 phosphorylation is", "il13ra1 phosphorylation is induced", "phosphorylation is induced only", "is induced only by", "induced only by il13", "by il13 roy", "al. 2002 laporte", "2002 laporte et", "al. 2008 and", "2008 and il2rg", "and il2rg phosphorylation is", "il2rg phosphorylation is induced", "induced only by il4", "by il4 roy", "il4 roy et", "et al. 2002 .

both", "al. 2002 .

both il4", "2002 .

both il4 receptor", ".

both il4 receptor complexes", "il4 receptor complexes signal", "receptor complexes signal through", "complexes signal through jak/stat", "signal through jak/stat cascades.", "through jak/stat cascades. il4r", "jak/stat cascades. il4r is", "cascades. il4r is constitutively", "il4r is constitutively associated", "is constitutively associated with", "constitutively associated with jak2", "with jak2 roy", "jak2 roy et", "al. 2002 and", "2002 and associates", "and associates with jak1", "associates with jak1 following", "with jak1 following binding", "jak1 following binding of", "following binding of il4", "of il4 yin", "il4 yin et", "yin et al. 1994", "al. 1994 or", "1994 or il13", "or il13 roy", "et al. 2002 .", "al. 2002 . il2rg", "2002 . il2rg constitutively", ". il2rg constitutively associates", "il2rg constitutively associates with", "constitutively associates with jak3", "with jak3 boussiotis", "jak3 boussiotis et", "boussiotis et al. 1994", "al. 1994 russell", "russell et al.", "et al. 1994 .", "al. 1994 . il13ra1", "1994 . il13ra1 constitutively", ". il13ra1 constitutively associates", "il13ra1 constitutively associates with", "constitutively associates with tyk2", "with tyk2 umeshita", "tyk2 umeshita suyama", "umeshita suyama et al.", "suyama et al. 2000", "al. 2000 roy", "2000 roy et", "al. 2008 bhattacharjee", "2008 bhattacharjee et", "bhattacharjee et al. 2013", "et al. 2013 .", "al. 2013 .

il4", "2013 .

il4 binding", ".

il4 binding to", "

il4 binding to il4r1", "binding to il4r1 leads", "to il4r1 leads to", "il4r1 leads to phosphorylation", "leads to phosphorylation of", "to phosphorylation of jak1", "of jak1 but", "jak1 but not", "not jak2 and", "jak2 and stat6", "stat6 activation takeda", "activation takeda et", "takeda et al. 1994", "al. 1994 ratthe", "1994 ratthe et", "ratthe et al. 2007", "al. 2007 bhattacharjee", "2007 bhattacharjee et", "al. 2013 .

il13", "2013 .

il13 binding", ".

il13 binding increases", "

il13 binding increases activating", "binding increases activating tyrosine", "increases activating tyrosine 99", "activating tyrosine 99 phosphorylation", "tyrosine 99 phosphorylation of", "99 phosphorylation of il13ra1", "phosphorylation of il13ra1 but", "of il13ra1 but not", "il13ra1 but not that", "but not that of", "not that of il2rg.", "that of il2rg. il4", "of il2rg. il4 binding", "il2rg. il4 binding to", "il4 binding to il2rg", "binding to il2rg leads", "to il2rg leads to", "il2rg leads to its", "leads to its tyrosine", "to its tyrosine phosphorylation", "tyrosine phosphorylation roy", "phosphorylation roy et", "al. 2002 . il13", "2002 . il13 binding", ". il13 binding to", "il13 binding to il4r2", "binding to il4r2 leads", "to il4r2 leads to", "il4r2 leads to tyk2", "leads to tyk2 and", "to tyk2 and jak2", "and jak2 but", "jak2 but not", "not jak1 phosphorylation", "phosphorylation roy &", "roy & cathcart 1998", "cathcart 1998 roy", "1998 roy et", "et al. 2002 .

phosphorylated", "al. 2002 .

phosphorylated tyk2", "2002 .

phosphorylated tyk2 binds", ".

phosphorylated tyk2 binds and", "tyk2 binds and phosphorylates", "binds and phosphorylates stat6", "and phosphorylates stat6 and", "phosphorylates stat6 and possibly", "stat6 and possibly stat1", "possibly stat1 bhattacharjee", "stat1 bhattacharjee et", "2013 .

a", ".

a second", "

a second mechanism of", "second mechanism of signal", "mechanism of signal transduction", "of signal transduction activated", "signal transduction activated by", "transduction activated by il4", "activated by il4 and", "by il4 and il13", "il4 and il13 leads", "and il13 leads to", "il13 leads to the", "leads to the insulin", "to the insulin receptor", "the insulin receptor substrate", "receptor substrate irs", "family kelly welch", "kelly welch et al.", "welch et al. 2003", "al. 2003 . il4r1", "2003 . il4r1 associates", ". il4r1 associates with", "il4r1 associates with insulin", "associates with insulin receptor", "with insulin receptor substrate", "insulin receptor substrate 2", "receptor substrate 2 and", "substrate 2 and activates", "2 and activates the", "and activates the pi3k/akt", "activates the pi3k/akt and", "the pi3k/akt and ras/mek/erk", "pi3k/akt and ras/mek/erk pathways", "and ras/mek/erk pathways involved", "ras/mek/erk pathways involved in", "pathways involved in cell", "involved in cell proliferation", "cell proliferation survival", "proliferation survival and", "survival and translational control.", "and translational control. il4r2", "translational control. il4r2 does", "control. il4r2 does not", "il4r2 does not associate", "does not associate with", "not associate with insulin", "associate with insulin receptor", "substrate 2 and consequently", "2 and consequently the", "and consequently the pi3k/akt", "consequently the pi3k/akt and", "and ras/mek/erk pathways are", "ras/mek/erk pathways are not", "pathways are not activated", "not activated busch", "activated busch dienstfertig", "busch dienstfertig & gonz\u00e1lez", "dienstfertig & gonz\u00e1lez rodr\u00edguez", "& gonz\u00e1lez rodr\u00edguez 2013", "gonz\u00e1lez rodr\u00edguez 2013 .", "4 il4 is", "il4 is a principal", "is a principal regulatory cytokine", "a principal regulatory cytokine during", "principal regulatory cytokine during the", "regulatory cytokine during the immune", "cytokine during the immune response", "the immune response crucially", "immune response crucially important", "response crucially important in", "crucially important in allergy and", "important in allergy and asthma", "allergy and asthma nelms", "and asthma nelms et", "asthma nelms et al.", "nelms et al. 1999 .", "et al. 1999 . when", "al. 1999 . when resting", "1999 . when resting t", ". when resting t cells", "when resting t cells are", "resting t cells are antigen", "t cells are antigen activated", "cells are antigen activated and", "are antigen activated and expand", "antigen activated and expand in", "activated and expand in response", "and expand in response to", "expand in response to interleukin", "in response to interleukin 2", "to interleukin 2 il2", "il2 they can", "they can differentiate as type", "can differentiate as type 1", "as type 1 th1", "1 th1 or", "th1 or type 2", "or type 2 th2", "2 th2 t", "th2 t helper cells.", "t helper cells. the outcome", "helper cells. the outcome is", "cells. the outcome is influenced", "the outcome is influenced by", "outcome is influenced by il4.", "is influenced by il4. th2", "influenced by il4. th2 cells", "by il4. th2 cells secrete", "il4. th2 cells secrete il4", "cells secrete il4 which", "secrete il4 which both", "il4 which both stimulates", "which both stimulates th2 in", "both stimulates th2 in an", "stimulates th2 in an autocrine", "th2 in an autocrine fashion", "in an autocrine fashion and", "an autocrine fashion and acts", "autocrine fashion and acts as", "fashion and acts as a", "and acts as a potent", "acts as a potent b", "as a potent b cell", "a potent b cell growth", "potent b cell growth factor", "b cell growth factor to", "cell growth factor to promote", "growth factor to promote humoral", "factor to promote humoral immunity", "promote humoral immunity nelms", "humoral immunity nelms et", "immunity nelms et al.", "et al. 1999 .

interleukin", "al. 1999 .

interleukin 13", ".

interleukin 13 il13", "13 il13 is", "il13 is an immunoregulatory", "is an immunoregulatory cytokine secreted", "an immunoregulatory cytokine secreted predominantly", "immunoregulatory cytokine secreted predominantly by", "cytokine secreted predominantly by activated", "secreted predominantly by activated th2", "predominantly by activated th2 cells.", "by activated th2 cells. it", "activated th2 cells. it is", "th2 cells. it is a", "cells. it is a key", "it is a key mediator", "is a key mediator in", "a key mediator in the", "key mediator in the pathogenesis", "mediator in the pathogenesis of", "in the pathogenesis of allergic", "the pathogenesis of allergic inflammation.", "pathogenesis of allergic inflammation. il13", "of allergic inflammation. il13 shares", "allergic inflammation. il13 shares many", "inflammation. il13 shares many functional", "il13 shares many functional properties", "shares many functional properties with", "many functional properties with il4", "properties with il4 stemming", "with il4 stemming from", "il4 stemming from the", "stemming from the fact that", "from the fact that they", "the fact that they share", "fact that they share a", "that they share a common", "they share a common receptor", "share a common receptor subunit.", "a common receptor subunit. il13", "common receptor subunit. il13 receptors", "receptor subunit. il13 receptors are", "subunit. il13 receptors are expressed", "il13 receptors are expressed on", "receptors are expressed on human", "are expressed on human b", "expressed on human b cells", "human b cells basophils", "cells basophils eosinophils", "basophils eosinophils mast", "mast cells endothelial cells", "cells fibroblasts monocytes", "fibroblasts monocytes macrophages", "monocytes macrophages respiratory", "macrophages respiratory epithelial cells", "respiratory epithelial cells and", "epithelial cells and smooth", "cells and smooth muscle", "smooth muscle cells but", "muscle cells but unlike", "cells but unlike il4", "but unlike il4 not", "unlike il4 not t", "il4 not t cells.", "not t cells. thus il13", "t cells. thus il13 does", "cells. thus il13 does not", "thus il13 does not appear", "il13 does not appear to", "does not appear to be", "not appear to be important", "appear to be important in", "to be important in the", "be important in the initial", "important in the initial differentiation", "in the initial differentiation of", "the initial differentiation of cd4", "initial differentiation of cd4 t", "differentiation of cd4 t cells", "of cd4 t cells into", "cd4 t cells into th2", "t cells into th2 cells", "into th2 cells rather", "th2 cells rather it", "cells rather it is", "rather it is important in", "it is important in the", "is important in the effector", "important in the effector phase", "in the effector phase of", "the effector phase of allergic", "effector phase of allergic inflammation", "of allergic inflammation hershey", "allergic inflammation hershey et", "inflammation hershey et al.", "hershey et al. 2003 .", "et al. 2003 . il4", "al. 2003 . il4 and", "2003 . il4 and il13", ". il4 and il13 induce", "il4 and il13 induce \u201calternative", "and il13 induce \u201calternative activation\u201d", "il13 induce \u201calternative activation\u201d of", "induce \u201calternative activation\u201d of macrophages", "activation\u201d of macrophages inducing", "of macrophages inducing an", "macrophages inducing an anti", "inducing an anti inflammatory phenotype", "an anti inflammatory phenotype by", "anti inflammatory phenotype by signaling", "inflammatory phenotype by signaling through", "phenotype by signaling through il4r", "by signaling through il4r alpha", "signaling through il4r alpha in", "through il4r alpha in a", "il4r alpha in a stat6", "alpha in a stat6 dependent", "in a stat6 dependent manner.", "a stat6 dependent manner. this", "stat6 dependent manner. this signaling", "dependent manner. this signaling plays", "manner. this signaling plays an", "this signaling plays an important", "signaling plays an important role", "plays an important role in", "an important role in the", "important role in the th2", "role in the th2 response", "the th2 response mediating", "th2 response mediating anti", "response mediating anti parasitic", "mediating anti parasitic effects and", "anti parasitic effects and aiding", "parasitic effects and aiding wound", "effects and aiding wound healing", "aiding wound healing gordon", "wound healing gordon &", "healing gordon & martinez", "& martinez 2010 loke", "martinez 2010 loke et", "2010 loke et al.", "et al. 2002 there", "al. 2002 there are", "2002 there are two", "there are two types of", "are two types of il4", "two types of il4 receptor", "types of il4 receptor complex", "il4 receptor complex andrews", "receptor complex andrews et", "complex andrews et al.", "andrews et al. 2006 .", "et al. 2006 . type", "al. 2006 . type i", "2006 . type i il4r", "type i il4r il4r1", "il4r il4r1 is", "il4r1 is predominantly expressed", "is predominantly expressed on the", "predominantly expressed on the surface", "expressed on the surface of", "on the surface of hematopoietic", "the surface of hematopoietic cells", "surface of hematopoietic cells and", "of hematopoietic cells and consists", "hematopoietic cells and consists of", "cells and consists of il4r", "and consists of il4r and", "consists of il4r and il2rg", "il4r and il2rg the", "and il2rg the common", "il2rg the common gamma", "the common gamma chain. type", "common gamma chain. type ii", "gamma chain. type ii il4r", "type ii il4r il4r2", "il4r il4r2 is", "il4r2 is predominantly expressed", "on the surface of nonhematopoietic", "the surface of nonhematopoietic cells", "of nonhematopoietic cells it", "nonhematopoietic cells it consists", "cells it consists of", "it consists of il4r and", "consists of il4r and il13ra1", "of il4r and il13ra1 and", "il4r and il13ra1 and is", "and il13ra1 and is also", "il13ra1 and is also the", "and is also the type", "is also the type ii", "also the type ii receptor", "the type ii receptor for", "type ii receptor for il13.", "receptor for il13. obiri", "for il13. obiri et", "il13. obiri et al.", "et al. 1995 aman", "al. 1995 aman et", "1995 aman et al.", "et al. 1996 hilton", "al. 1996 hilton et", "1996 hilton et al.", "et al. 1996 miloux", "al. 1996 miloux et", "1996 miloux et al.", "et al. 1997 zhang", "al. 1997 zhang et", "1997 zhang et al.", "zhang et al. 1997 .", "et al. 1997 . the", "al. 1997 . the second", "1997 . the second receptor", ". the second receptor for", "the second receptor for il13", "second receptor for il13 consists", "receptor for il13 consists of", "for il13 consists of il4r", "il13 consists of il4r and", "consists of il4r and interleukin", "of il4r and interleukin 13", "il4r and interleukin 13 receptor", "and interleukin 13 receptor alpha", "interleukin 13 receptor alpha 2", "receptor alpha 2 il13ra2", "il13ra2 sometimes called", "sometimes called interleukin 13 binding", "called interleukin 13 binding protein", "13 binding protein il13bp", "binding protein il13bp .", "protein il13bp . it", "il13bp . it has a", ". it has a high", "it has a high affinity", "has a high affinity receptor", "a high affinity receptor for", "high affinity receptor for il13", "receptor for il13 kd", "for il13 kd =", "il13 kd = 250", "= 250 pmol/l but", "250 pmol/l but is", "pmol/l but is not", "but is not sufficient to", "is not sufficient to render", "not sufficient to render cells", "sufficient to render cells responsive", "to render cells responsive to", "render cells responsive to il13", "responsive to il13 even", "to il13 even in", "il13 even in the", "even in the presence of", "in the presence of il4r", "presence of il4r donaldson", "of il4r donaldson et", "il4r donaldson et al.", "donaldson et al. 1998 .", "et al. 1998 . it", "al. 1998 . it is", "1998 . it is reported", ". it is reported to", "it is reported to exist", "is reported to exist in", "reported to exist in soluble", "to exist in soluble form", "in soluble form zhang", "soluble form zhang et", "form zhang et al.", "et al. 1997 and", "al. 1997 and when", "1997 and when overexpressed", "and when overexpressed reduces jak", "when overexpressed reduces jak stat", "overexpressed reduces jak stat signaling", "jak stat signaling kawakami", "stat signaling kawakami et", "signaling kawakami et al.", "kawakami et al. 2001 .", "et al. 2001 . it's", "al. 2001 . it's function", "2001 . it's function may", ". it's function may be", "it's function may be to", "function may be to prevent", "may be to prevent il13", "be to prevent il13 signalling", "to prevent il13 signalling via", "prevent il13 signalling via the", "il13 signalling via the functional", "signalling via the functional il4r:il13ra1", "via the functional il4r:il13ra1 receptor.", "the functional il4r:il13ra1 receptor. il13ra2", "functional il4r:il13ra1 receptor. il13ra2 is", "il4r:il13ra1 receptor. il13ra2 is overexpressed", "receptor. il13ra2 is overexpressed and", "il13ra2 is overexpressed and enhances", "is overexpressed and enhances cell", "overexpressed and enhances cell invasion", "and enhances cell invasion in", "enhances cell invasion in some", "cell invasion in some human", "invasion in some human cancers", "some human cancers joshi", "human cancers joshi &", "cancers joshi & puri", "joshi & puri 2012 .

the", "& puri 2012 .

the first", "puri 2012 .

the first step", "2012 .

the first step in", ".

the first step in the", "first step in the formation", "step in the formation of", "in the formation of il4r1", "formation of il4r1 il4:il4r:il2rb", "il4r1 il4:il4r:il2rb is", "il4:il4r:il2rb is the binding", "is the binding of il4", "the binding of il4 with", "binding of il4 with il4r", "il4 with il4r hoffman", "with il4r hoffman et", "il4r hoffman et al.", "et al. 1995 shen", "al. 1995 shen et", "1995 shen et al.", "et al. 1996 hage", "al. 1996 hage et", "1996 hage et al.", "hage et al. 1999 .", "et al. 1999 . this", "al. 1999 . this is", "1999 . this is also", ". this is also the", "this is also the first", "is also the first step", "also the first step in", "the first step in formation", "first step in formation of", "step in formation of il4r2", "formation of il4r2 il4:il4r:il13ra1", "of il4r2 il4:il4r:il13ra1 .", "il4r2 il4:il4r:il13ra1 . after", "il4:il4r:il13ra1 . after the initial", ". after the initial binding", "after the initial binding of", "the initial binding of il4", "initial binding of il4 and", "binding of il4 and il4r", "il4 and il4r il2rb", "and il4r il2rb binds", "il2rb binds laporte et", "binds laporte et al.", "al. 2008 to", "2008 to form", "form il4r1. alternatively il13ra1", "il4r1. alternatively il13ra1 binds", "il13ra1 binds forming il4r2.", "binds forming il4r2. in", "il4r2. in contrast the", "in contrast the type", "contrast the type ii", "the type ii il13 complex", "ii il13 complex il13r2", "complex il13r2 forms", "il13r2 forms with il13", "forms with il13 first binding", "with il13 first binding to", "il13 first binding to il13ra1", "first binding to il13ra1 followed", "binding to il13ra1 followed by", "to il13ra1 followed by recruitment", "il13ra1 followed by recruitment of", "by recruitment of il4r", "of il4r wang", "il4r wang et al.", "wang et al. 2009 .

crystal", "et al. 2009 .

crystal structures", "al. 2009 .

crystal structures of", "2009 .

crystal structures of the", ".

crystal structures of the il4:il4r:il2rg", "of the il4:il4r:il2rg il4:il4r:il13ra1", "the il4:il4r:il2rg il4:il4r:il13ra1 and", "il4:il4r:il2rg il4:il4r:il13ra1 and il13:il4r:il13ra1", "il4:il4r:il13ra1 and il13:il4r:il13ra1 complexes have", "and il13:il4r:il13ra1 complexes have been", "il13:il4r:il13ra1 complexes have been determined", "have been determined laporte", "been determined laporte et", "determined laporte et al.", "laporte et al. 2008 .", "et al. 2008 . consistent", "al. 2008 . consistent with", "2008 . consistent with these", ". consistent with these structures", "with these structures in", "these structures in monocytes", "structures in monocytes il4r", "in monocytes il4r is tyrosine", "monocytes il4r is tyrosine phosphorylated", "il4r is tyrosine phosphorylated in", "is tyrosine phosphorylated in response", "tyrosine phosphorylated in response to", "phosphorylated in response to both", "in response to both il4", "response to both il4 and", "to both il4 and il13", "il4 and il13 roy", "and il13 roy et", "il13 roy et al.", "et al. 2002 gordon", "al. 2002 gordon &", "2002 gordon & martinez", "& martinez 2010 while", "martinez 2010 while il13ra1", "2010 while il13ra1 phosphorylation", "while il13ra1 phosphorylation is induced", "il13ra1 phosphorylation is induced only", "phosphorylation is induced only by", "is induced only by il13", "only by il13 roy", "by il13 roy et", "et al. 2002 laporte", "al. 2002 laporte et", "2002 laporte et al.", "et al. 2008 and", "al. 2008 and il2rg", "2008 and il2rg phosphorylation", "and il2rg phosphorylation is induced", "il2rg phosphorylation is induced only", "is induced only by il4", "only by il4 roy", "by il4 roy et", "il4 roy et al.", "roy et al. 2002 .

both", "et al. 2002 .

both il4", "al. 2002 .

both il4 receptor", "2002 .

both il4 receptor complexes", ".

both il4 receptor complexes signal", "il4 receptor complexes signal through", "receptor complexes signal through jak/stat", "complexes signal through jak/stat cascades.", "signal through jak/stat cascades. il4r", "through jak/stat cascades. il4r is", "jak/stat cascades. il4r is constitutively", "cascades. il4r is constitutively associated", "il4r is constitutively associated with", "is constitutively associated with jak2", "associated with jak2 roy", "with jak2 roy et", "jak2 roy et al.", "et al. 2002 and", "al. 2002 and associates", "2002 and associates with", "and associates with jak1 following", "associates with jak1 following binding", "with jak1 following binding of", "jak1 following binding of il4", "binding of il4 yin", "of il4 yin et", "il4 yin et al.", "et al. 1994 or", "al. 1994 or il13", "or il13 roy et", "roy et al. 2002 .", "et al. 2002 . il2rg", "al. 2002 . il2rg constitutively", "2002 . il2rg constitutively associates", ". il2rg constitutively associates with", "il2rg constitutively associates with jak3", "associates with jak3 boussiotis", "with jak3 boussiotis et", "jak3 boussiotis et al.", "et al. 1994 russell", "1994 russell et", "russell et al. 1994", "et al. 1994 . il13ra1", "al. 1994 . il13ra1 constitutively", "1994 . il13ra1 constitutively associates", ". il13ra1 constitutively associates with", "il13ra1 constitutively associates with tyk2", "associates with tyk2 umeshita", "with tyk2 umeshita suyama", "tyk2 umeshita suyama et", "umeshita suyama et al. 2000", "et al. 2000 roy", "al. 2000 roy et", "2000 roy et al.", "et al. 2008 bhattacharjee", "al. 2008 bhattacharjee et", "2008 bhattacharjee et al.", "bhattacharjee et al. 2013 .", "et al. 2013 .

il4", "al. 2013 .

il4 binding", "2013 .

il4 binding to", ".

il4 binding to il4r1", "

il4 binding to il4r1 leads", "binding to il4r1 leads to", "to il4r1 leads to phosphorylation", "il4r1 leads to phosphorylation of", "leads to phosphorylation of jak1", "phosphorylation of jak1 but", "of jak1 but not", "jak1 but not jak2", "but not jak2 and", "not jak2 and stat6", "jak2 and stat6 activation", "and stat6 activation takeda", "stat6 activation takeda et", "activation takeda et al.", "et al. 1994 ratthe", "al. 1994 ratthe et", "1994 ratthe et al.", "et al. 2007 bhattacharjee", "al. 2007 bhattacharjee et", "2007 bhattacharjee et al.", "et al. 2013 .

il13", "al. 2013 .

il13 binding", "2013 .

il13 binding increases", ".

il13 binding increases activating", "

il13 binding increases activating tyrosine", "binding increases activating tyrosine 99", "increases activating tyrosine 99 phosphorylation", "activating tyrosine 99 phosphorylation of", "tyrosine 99 phosphorylation of il13ra1", "99 phosphorylation of il13ra1 but", "phosphorylation of il13ra1 but not", "of il13ra1 but not that", "il13ra1 but not that of", "but not that of il2rg.", "not that of il2rg. il4", "that of il2rg. il4 binding", "of il2rg. il4 binding to", "il2rg. il4 binding to il2rg", "il4 binding to il2rg leads", "binding to il2rg leads to", "to il2rg leads to its", "il2rg leads to its tyrosine", "leads to its tyrosine phosphorylation", "its tyrosine phosphorylation roy", "tyrosine phosphorylation roy et", "phosphorylation roy et al.", "et al. 2002 . il13", "al. 2002 . il13 binding", "2002 . il13 binding to", ". il13 binding to il4r2", "il13 binding to il4r2 leads", "binding to il4r2 leads to", "to il4r2 leads to tyk2", "il4r2 leads to tyk2 and", "leads to tyk2 and jak2", "tyk2 and jak2 but", "and jak2 but not", "jak2 but not jak1", "but not jak1 phosphorylation", "jak1 phosphorylation roy", "phosphorylation roy & cathcart", "& cathcart 1998 roy", "cathcart 1998 roy et", "1998 roy et al.", "roy et al. 2002 .

phosphorylated", "et al. 2002 .

phosphorylated tyk2", "al. 2002 .

phosphorylated tyk2 binds", "2002 .

phosphorylated tyk2 binds and", ".

phosphorylated tyk2 binds and phosphorylates", "tyk2 binds and phosphorylates stat6", "binds and phosphorylates stat6 and", "and phosphorylates stat6 and possibly", "phosphorylates stat6 and possibly stat1", "and possibly stat1 bhattacharjee", "possibly stat1 bhattacharjee et", "stat1 bhattacharjee et al.", "al. 2013 .

a", "2013 .

a second", ".

a second mechanism", "

a second mechanism of signal", "second mechanism of signal transduction", "mechanism of signal transduction activated", "of signal transduction activated by", "signal transduction activated by il4", "transduction activated by il4 and", "activated by il4 and il13", "by il4 and il13 leads", "il4 and il13 leads to", "and il13 leads to the", "il13 leads to the insulin", "leads to the insulin receptor", "to the insulin receptor substrate", "insulin receptor substrate irs", "substrate irs family", "irs family kelly", "family kelly welch et", "kelly welch et al. 2003", "welch et al. 2003 .", "et al. 2003 . il4r1", "al. 2003 . il4r1 associates", "2003 . il4r1 associates with", ". il4r1 associates with insulin", "il4r1 associates with insulin receptor", "associates with insulin receptor substrate", "with insulin receptor substrate 2", "insulin receptor substrate 2 and", "receptor substrate 2 and activates", "substrate 2 and activates the", "2 and activates the pi3k/akt", "and activates the pi3k/akt and", "activates the pi3k/akt and ras/mek/erk", "the pi3k/akt and ras/mek/erk pathways", "pi3k/akt and ras/mek/erk pathways involved", "and ras/mek/erk pathways involved in", "ras/mek/erk pathways involved in cell", "pathways involved in cell proliferation", "in cell proliferation survival", "cell proliferation survival and", "proliferation survival and translational", "survival and translational control. il4r2", "and translational control. il4r2 does", "translational control. il4r2 does not", "control. il4r2 does not associate", "il4r2 does not associate with", "does not associate with insulin", "not associate with insulin receptor", "associate with insulin receptor substrate", "receptor substrate 2 and consequently", "substrate 2 and consequently the", "2 and consequently the pi3k/akt", "and consequently the pi3k/akt and", "consequently the pi3k/akt and ras/mek/erk", "pi3k/akt and ras/mek/erk pathways are", "and ras/mek/erk pathways are not", "ras/mek/erk pathways are not activated", "are not activated busch", "not activated busch dienstfertig", "activated busch dienstfertig &", "busch dienstfertig & gonz\u00e1lez rodr\u00edguez", "dienstfertig & gonz\u00e1lez rodr\u00edguez 2013", "& gonz\u00e1lez rodr\u00edguez 2013 ." ] }, { "record_id": "GLY_000594_1_513", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6787450", "r hsa", "hsa 6787450", "r hsa 6787450" ] }, { "record_id": "GLY_000594_1_513", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "trna modification", "modification in", "in the", "the mitochondrion", "trna modification in", "modification in the", "in the mitochondrion", "trna modification in the", "modification in the mitochondrion", "trna modification in the mitochondrion", "the 22", "22 trnas", "trnas encoded", "encoded by", "by the", "the mitochondrial", "mitochondrial genome", "genome are", "are modified", "modified in", "mitochondrial matrix", "matrix by", "by enzymes", "enzymes encoded", "encoded in", "the nucleus", "nucleus and", "and imported", "imported into", "into mitochondria", "reviewed in", "in suzuki", "suzuki et", "et al.", "al. 2011", "salinas giege", "giege et", "al. 2015", "2015 .", ". some", "some enzymes", "enzymes such", "such as", "as pus1", "pus1 and", "and trit1", "trit1 are", "are located", "located in", "in more", "more than", "than one", "one compartment", "compartment and", "and modify", "modify both", "both mitochondrial", "mitochondrial trnas", "trnas and", "and cytosolic", "cytosolic trnas.", "trnas. other", "other enzymes", "as mto1", "and trmt61b", "trmt61b are", "are exclusively", "mitochondrial.
modifications near", "near the", "the anticodon", "anticodon and", "and near", "the 3'", "3' end", "end of", "of trnas", "trnas tend", "tend to", "to affect", "affect interaction", "interaction of", "of the", "the trna", "trna with", "with mrna", "mrna within", "within ribosomes", "ribosomes and", "and with", "with trna", "trna synthetases", "respectively. modifications", "modifications in", "in other", "other regions", "typically in", "the \\core\\", "\\core\\ of", "trna tend", "affect folding", "folding and", "and stability", "stability of", "in hou", "hou et", ". the", "the unusual", "unusual modification", "modification 5", "5 taurinomethyl", "taurinomethyl 2", "2 thiouridine", "thiouridine 34", "34 in", "anticodon of", "of at", "at least", "least 3", "3 trnas", "trnas is", "is found", "found only", "only in", "in mammalian", "mammalian mitochondria", "mitochondria and", "and mutations", "mutations that", "that affect", "affect the", "the responsible", "responsible biosynthetic", "biosynthetic enzymes", "cause mitochondrial", "mitochondrial dysfunction", "dysfunction and", "and disease", "in torres", "torres et", "al. 2014", "2014 .", "the 22 trnas", "22 trnas encoded", "trnas encoded by", "encoded by the", "by the mitochondrial", "the mitochondrial genome", "mitochondrial genome are", "genome are modified", "are modified in", "modified in the", "in the mitochondrial", "the mitochondrial matrix", "mitochondrial matrix by", "matrix by enzymes", "by enzymes encoded", "enzymes encoded in", "encoded in the", "in the nucleus", "the nucleus and", "nucleus and imported", "and imported into", "imported into mitochondria", "mitochondria reviewed", "reviewed in suzuki", "in suzuki et", "suzuki et al.", "et al. 2011", "2011 salinas", "salinas giege et", "giege et al.", "et al. 2015", "al. 2015 .", "2015 . some", ". some enzymes", "some enzymes such", "enzymes such as", "such as pus1", "as pus1 and", "pus1 and trit1", "and trit1 are", "trit1 are located", "are located in", "located in more", "in more than", "more than one", "than one compartment", "one compartment and", "compartment and modify", "and modify both", "modify both mitochondrial", "both mitochondrial trnas", "mitochondrial trnas and", "trnas and cytosolic", "and cytosolic trnas.", "cytosolic trnas. other", "trnas. other enzymes", "other enzymes such", "such as mto1", "mto1 trmu", "trmu and", "and trmt61b are", "trmt61b are exclusively", "exclusively mitochondrial.
modifications", "mitochondrial.
modifications near the", "near the anticodon", "the anticodon and", "anticodon and near", "and near the", "near the 3'", "the 3' end", "3' end of", "end of trnas", "of trnas tend", "trnas tend to", "tend to affect", "to affect interaction", "affect interaction of", "interaction of the", "of the trna", "the trna with", "trna with mrna", "with mrna within", "mrna within ribosomes", "within ribosomes and", "ribosomes and with", "and with trna", "with trna synthetases", "synthetases respectively.", "respectively. modifications in", "modifications in other", "in other regions", "regions typically", "typically in the", "in the \\core\\", "the \\core\\ of", "\\core\\ of the", "the trna tend", "trna tend to", "to affect folding", "affect folding and", "folding and stability", "and stability of", "stability of the", "trna reviewed", "reviewed in hou", "in hou et", "hou et al.", "2015 . the", ". the unusual", "the unusual modification", "unusual modification 5", "modification 5 taurinomethyl", "5 taurinomethyl 2", "taurinomethyl 2 thiouridine", "2 thiouridine 34", "thiouridine 34 in", "34 in the", "in the anticodon", "the anticodon of", "anticodon of at", "of at least", "at least 3", "least 3 trnas", "3 trnas is", "trnas is found", "is found only", "found only in", "only in mammalian", "in mammalian mitochondria", "mammalian mitochondria and", "mitochondria and mutations", "and mutations that", "mutations that affect", "that affect the", "affect the responsible", "the responsible biosynthetic", "responsible biosynthetic enzymes", "enzymes gtpbp3", "gtpbp3 mto1", "trmu cause", "cause mitochondrial dysfunction", "mitochondrial dysfunction and", "dysfunction and disease", "disease reviewed", "reviewed in torres", "in torres et", "torres et al.", "et al. 2014", "al. 2014 .", "the 22 trnas encoded", "22 trnas encoded by", "trnas encoded by the", "encoded by the mitochondrial", "by the mitochondrial genome", "the mitochondrial genome are", "mitochondrial genome are modified", "genome are modified in", "are modified in the", "modified in the mitochondrial", "in the mitochondrial matrix", "the mitochondrial matrix by", "mitochondrial matrix by enzymes", "matrix by enzymes encoded", "by enzymes encoded in", "enzymes encoded in the", "encoded in the nucleus", "in the nucleus and", "the nucleus and imported", "nucleus and imported into", "and imported into mitochondria", "into mitochondria reviewed", "mitochondria reviewed in", "reviewed in suzuki et", "in suzuki et al.", "suzuki et al. 2011", "al. 2011 salinas", "2011 salinas giege", "salinas giege et al.", "giege et al. 2015", "et al. 2015 .", "al. 2015 . some", "2015 . some enzymes", ". some enzymes such", "some enzymes such as", "enzymes such as pus1", "such as pus1 and", "as pus1 and trit1", "pus1 and trit1 are", "and trit1 are located", "trit1 are located in", "are located in more", "located in more than", "in more than one", "more than one compartment", "than one compartment and", "one compartment and modify", "compartment and modify both", "and modify both mitochondrial", "modify both mitochondrial trnas", "both mitochondrial trnas and", "mitochondrial trnas and cytosolic", "trnas and cytosolic trnas.", "and cytosolic trnas. other", "cytosolic trnas. other enzymes", "trnas. other enzymes such", "other enzymes such as", "enzymes such as mto1", "as mto1 trmu", "trmu and trmt61b", "and trmt61b are exclusively", "are exclusively mitochondrial.
modifications", "exclusively mitochondrial.
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and modify nucleotides.", "rrna and modify nucleotides. through", "and modify nucleotides. through addition", "modify nucleotides. through addition of", "nucleotides. through addition of subunits", "through addition of subunits the", "addition of subunits the ssu", "of subunits the ssu processome", "subunits the ssu processome appears", "the ssu processome appears to", "ssu processome appears to be", "processome appears to be converted", "appears to be converted into", "to be converted into the", "be converted into the larger", "converted into the larger 90s", "into the larger 90s pre", "the larger 90s pre ribosome", "90s pre ribosome inferred", "pre ribosome inferred from", "ribosome inferred from yeast", "inferred from yeast in grandi", "from yeast in grandi et", "yeast in grandi et al.", "in grandi et al. 2002", "grandi et al. 2002 .", "et al. 2002 . an", "al. 2002 . an analogous", "2002 . an analogous large", ". an analogous large subunit", "an analogous large subunit processome", 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expression", "2016 .

expression of", ".

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expression", "al. 2016 .

expression of", "2016 .

expression of several", ".

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tp53", "genes under genotoxic stress.

tp53 directly", "under genotoxic stress.

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tp53 directly stimulates transcription of", "directly stimulates transcription of several", "stimulates transcription of several genes", "transcription of several genes involved", "of several genes involved in", "several genes involved in dna", "genes involved in dna mismatch", "involved in dna mismatch repair", "dna mismatch repair including", "mismatch repair including msh2", "including msh2 scherer et", "msh2 scherer et al.", "et al. 2000 warnick", "al. 2000 warnick et", "2000 warnick et al.", "al. 2001 pms2", "2001 pms2 and", "pms2 and mlh1 chen", "and mlh1 chen and", "mlh1 chen and sadowski", "chen and sadowski 2005 .", "and sadowski 2005 . tp53", "sadowski 2005 . tp53 also", "2005 . tp53 also directly", ". tp53 also directly stimulates", "tp53 also directly stimulates transcription", "also directly stimulates transcription of", "directly stimulates transcription of ddb2", "transcription of ddb2 involved", "of ddb2 involved in", "ddb2 involved in nucleotide", "involved in nucleotide excision repair", "nucleotide excision repair tan", "excision repair tan and", "repair tan and chu", "chu 2002 and", "2002 and fancc", "and fancc involved in", "fancc involved in the", "involved in the fanconi anemia", "in the fanconi anemia pathway", "the fanconi anemia pathway that", "fanconi anemia pathway that repairs", "anemia pathway that repairs dna", "pathway that repairs dna interstrand", "that repairs dna interstrand crosslinks", "dna interstrand crosslinks liebetrau", "interstrand crosslinks liebetrau et", "crosslinks liebetrau et al.", "liebetrau et al. 1997 .", "et al. 1997 . other", "al. 1997 . other p53", "1997 . other p53 targets", ". other p53 targets that", "other p53 targets that can", "p53 targets that can influence", "targets that can influence dna", "that can influence dna repair", "can influence dna repair functions", "influence dna repair functions are", "dna repair functions are rrm2b", "functions are rrm2b kuo", "are rrm2b kuo et", "rrm2b kuo et al.", "al. 2012 xpc", "xpc fitch et al.", "al. 2003 gadd45a", "gadd45a amundson et al.", "al. 2002 cdkn1a", "cdkn1a cazzalini et al.", "et al. 2010 and", "al. 2010 and pcna", "and pcna xu and", "pcna xu and morris", "xu and morris 1999 .", "and morris 1999 . interestingly", "1999 . interestingly the", ". interestingly the responsiveness", "interestingly the responsiveness of", "the responsiveness of some of", "responsiveness of some of these", "of some of these dna", "some of these dna repair", "of these dna repair genes", "these dna repair genes to", "dna repair genes to p53", "repair genes to p53 activation", "genes to p53 activation has", "to p53 activation has been", "p53 activation has been shown", "activation has been shown in", "has been shown in human", "been shown in human cells", "shown in human cells but", "in human cells but not", "human cells but not for", "cells but not for orthologous", "but not for orthologous mouse", "not for orthologous mouse genes", "orthologous mouse genes jegga", "mouse genes jegga et", "genes jegga et al.", "et al. 2008 tan", "al. 2008 tan and", "2008 tan and chu", "tan and chu 2002 .", "and chu 2002 . contrary", "chu 2002 . contrary to", "2002 . contrary to the", ". contrary to the positive", "contrary to the positive modulation", "to the positive modulation of", "the positive modulation of nucleotide", "positive modulation of nucleotide excision", "modulation of nucleotide excision repair", "nucleotide excision repair ner", "repair ner and", "ner and mismatch repair", "and mismatch repair mmr", "mmr p53 can", "p53 can negatively modulate base", "can negatively modulate base excision", "negatively modulate base excision repair", "base excision repair ber", "ber by down", "by down regulating the endonuclease", "down regulating the endonuclease apex1", "the endonuclease apex1 ape1", "ape1 acting in", "acting in concert with sp1", "concert with sp1 poletto", "with sp1 poletto et", "sp1 poletto et al.", "poletto et al. 2016 .

expression", "et al. 2016 .

expression of", "al. 2016 .

expression of several", "2016 .

expression of several dna", ".

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et", "2011 cheng et al.", "et al. 2012 bosken", "al. 2012 bosken et", "2012 bosken et al.", "et al. 2014 bartkowiak", "al. 2014 bartkowiak and", "2014 bartkowiak and greenleaf", "and greenleaf 2015 ekumi", "greenleaf 2015 ekumi et", "2015 ekumi et al.", "ekumi et al. 2015 ." ] }, { "record_id": "GLY_000594_1_519", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6798695", "r hsa", "hsa 6798695", "r hsa 6798695" ] }, { "record_id": "GLY_000594_1_519", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "neutrophil degranulation", "neutrophils are", "are the", "the most", "most abundant", "abundant leukocytes", "white blood", "blood cells", "indispensable in", "in defending", "defending the", "the body", "body against", "against invading", "invading microorganisms.", "microorganisms. in", "in response", "response to", "to infection", "neutrophils leave", "leave the", "the circulation", "circulation 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granules", ".

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", "

the", "
the classical", "classical granule", "granule subsets", "subsets are", "are azurophil", "azurophil or", "or primary", "primary granules", "secondary granules", "and gelatinase", "gelatinase granules", "gg .", ". neutrophils", "neutrophils also", "also contain", "contain exocytosable", "exocytosable storage", "storage cell", "cell organelles", "storage vesicles", "formed by", "by endocytosis", "endocytosis they", "contain many", "many cell", "surface markers", "markers and", "and extracellular", "plasma proteins", "al. 1992", "1992 .", ". ficolin", "ficolin 1", "1 rich", "rich granules", "are like", "like ggs", "ggs highly", "highly exocytosable", "exocytosable but", "but gelatinase", "gelatinase poor", "rorvig et", "al. 2009", "2009 .", "neutrophils are the", "are the most", "the most abundant", "most abundant leukocytes", "leukocytes white", "white blood cells", "indispensable in defending", "in defending the", "defending the body", "the body against", "body against invading", "against invading microorganisms.", "invading microorganisms. in", "microorganisms. in response", "in response to", "response to infection", "infection neutrophils", "neutrophils leave the", "leave the circulation", "the circulation and", "circulation and migrate", "and migrate towards", "migrate towards the", "towards the inflammatory", "the inflammatory focus.", "inflammatory focus. they", "focus. they contain", "they contain several", "contain several subsets", "several subsets of", "subsets of granules", "of granules that", "granules that are", "that are mobilized", "are mobilized to", "mobilized to fuse", "to fuse with", "fuse with the", "with the cell", "the cell membrane", "cell membrane or", "membrane or phagosomal", "or phagosomal membrane", "membrane resulting", "resulting in the", "in the exocytosis", "the exocytosis or", "exocytosis or exposure", "or exposure of", "exposure of membrane", "of membrane proteins.", "membrane proteins. traditionally", "traditionally neutrophil", "neutrophil granule constituents", "granule constituents are", "constituents are described", "are described as", "described as antimicrobial", "as antimicrobial or", "antimicrobial or proteolytic", "proteolytic but", "but granules also", "granules also introduce", "also introduce membrane", "introduce membrane proteins", "membrane proteins to", "proteins to the", "to the cell", "the cell surface", "surface changing", "changing how the", "how the neutrophil", "the neutrophil responds", "neutrophil responds to", "responds to its", "to its environment", "environment borregaard", "borregaard et al.", "et al. 2007", "al. 2007 .", "2007 . primed", ". primed neutrophils", "primed neutrophils actively", "neutrophils actively secrete", "actively secrete cytokines", "secrete cytokines and", "cytokines and other", "and other inflammatory", "other inflammatory mediators", "inflammatory mediators and", "mediators and can", "and can present", "can present antigens", "present antigens via", "antigens via mhc", "via mhc ii", "ii stimulating", "stimulating t cells", "cells wright", "wright et al.", "et al. 2010", "al. 2010 .

granules", "2010 .

granules form", ".

granules form during", "form during neutrophil", "during neutrophil differentiation.", "neutrophil differentiation. granule", "differentiation. granule subtypes", "granule subtypes can", "subtypes can be", "can be distinguished", "be distinguished by", "distinguished by their", "by their content", "their content but", "content but overlap", "but overlap in", "overlap in structure", "in structure and", "structure and composition.", "and composition. the", "composition. the differences", "the differences are", "differences are believed", "are believed to", "believed to be", "to be a", "be a consequence", "a consequence of", "consequence of changing", "of changing protein", "changing protein expression", "protein expression and", "expression and differential", "and differential timing", "differential timing of", "timing of granule", "of granule formation", "granule formation during", "formation during the", "during the terminal", "the terminal processes", "terminal processes of", "processes of neutrophil", "of neutrophil differentiation", "differentiation rather", "rather than sorting", "sorting le", "le cabec et", "cabec et al.", "et al. 1996", "al. 1996 .", "1996 .
", ".

the", "

the classical", "
the classical granule", "classical granule subsets", "granule subsets are", "subsets are azurophil", "are azurophil or", "azurophil or primary", "or primary granules", "granules ag", "granules sg", "sg and", "and gelatinase granules", "granules gg", "gg . neutrophils", ". neutrophils also", "neutrophils also contain", "also contain exocytosable", "contain exocytosable storage", "exocytosable storage cell", "storage cell organelles", "organelles storage", "vesicles sv", "formed by endocytosis", "by endocytosis they", "endocytosis they contain", "they contain many", "contain many cell", "many cell surface", "cell surface markers", "surface markers and", "markers and extracellular", "extracellular plasma", "proteins borregaard", "et al. 1992", "al. 1992 .", "1992 . ficolin", ". ficolin 1", "ficolin 1 rich", "1 rich granules", "granules fg", "fg are", "are like ggs", "like ggs highly", "ggs highly exocytosable", "highly exocytosable but", "exocytosable but gelatinase", "but gelatinase poor", "poor rorvig", "rorvig et al.", "et al. 2009", "al. 2009 .", "neutrophils are the most", "are the most abundant", "the most abundant leukocytes", "abundant leukocytes white", "leukocytes white blood", "cells indispensable", "indispensable in defending the", "in defending the body", "defending the body against", "the body against invading", "body against invading microorganisms.", "against invading microorganisms. in", "invading microorganisms. in response", "microorganisms. in response to", "in response to infection", "to infection neutrophils", "infection neutrophils leave", "neutrophils leave the circulation", "leave the circulation and", "the circulation and migrate", "circulation and migrate towards", "and migrate towards the", "migrate towards the inflammatory", "towards the inflammatory focus.", "the inflammatory focus. they", "inflammatory focus. they contain", "focus. they contain several", "they contain several subsets", "contain several subsets of", "several subsets of granules", "subsets of granules that", "of granules that are", "granules that are mobilized", "that are mobilized to", "are mobilized to fuse", "mobilized to fuse with", "to fuse with the", "fuse with the cell", "with the cell membrane", "the cell membrane or", "cell membrane or phagosomal", "membrane or phagosomal membrane", "phagosomal membrane resulting", "membrane resulting in", "resulting in the exocytosis", "in the exocytosis or", "the exocytosis or exposure", "exocytosis or exposure of", "or exposure of membrane", "exposure of membrane proteins.", "of membrane proteins. traditionally", "proteins. traditionally neutrophil", "traditionally neutrophil granule", "neutrophil granule constituents are", "granule constituents are described", "constituents are described as", "are described as antimicrobial", "described as antimicrobial or", "as antimicrobial or proteolytic", "or proteolytic but", "proteolytic but granules", "but granules also introduce", "granules also introduce membrane", "also introduce membrane proteins", "introduce membrane proteins to", "membrane proteins to the", "proteins to the cell", "to the cell surface", "cell surface changing", "surface changing how", "changing how the neutrophil", "how the neutrophil responds", "the neutrophil responds to", "neutrophil responds to its", "responds to its environment", "its environment borregaard", "environment borregaard et", "borregaard et al. 2007", "et al. 2007 .", "al. 2007 . primed", "2007 . primed neutrophils", ". primed neutrophils actively", "primed neutrophils actively secrete", "neutrophils actively secrete cytokines", "actively secrete cytokines and", "secrete cytokines and other", "cytokines and other inflammatory", "and other inflammatory mediators", "other inflammatory mediators and", "inflammatory mediators and can", "mediators and can present", "and can present antigens", "can present antigens via", "present antigens via mhc", "antigens via mhc ii", "mhc ii stimulating", "ii stimulating t", "t cells wright", "cells wright et", "wright et al. 2010", "et al. 2010 .

granules", "al. 2010 .

granules form", "2010 .

granules form during", ".

granules form during neutrophil", "form during neutrophil differentiation.", "during neutrophil differentiation. granule", "neutrophil differentiation. granule subtypes", "differentiation. granule subtypes can", "granule subtypes can be", "subtypes can be distinguished", "can be distinguished by", "be distinguished by their", "distinguished by their content", "by their content but", "their content but overlap", "content but overlap in", "but overlap in structure", "overlap in structure and", "in structure and composition.", "structure and composition. the", "and composition. the differences", "composition. the differences are", "the differences are believed", "differences are believed to", "are believed to be", "believed to be a", "to be a consequence", "be a consequence of", "a consequence of changing", "consequence of changing protein", "of changing protein expression", "changing protein expression and", "protein expression and differential", "expression and differential timing", "and differential timing of", "differential timing of granule", "timing of granule formation", "of granule formation during", "granule formation during the", "formation during the terminal", "during the terminal processes", "the terminal processes of", "terminal processes of neutrophil", "processes of neutrophil differentiation", "neutrophil differentiation rather", "differentiation rather than", "than sorting le", "sorting le cabec", "le cabec et al.", "cabec et al. 1996", "et al. 1996 .", "al. 1996 .
", "1996 .

the", ".

the classical", "

the classical granule", "
the classical granule subsets", "classical granule subsets are", "granule subsets are azurophil", "subsets are azurophil or", "are azurophil or primary", "azurophil or primary granules", "primary granules ag", "ag secondary", "secondary granules sg", "sg and gelatinase", "gelatinase granules gg", "granules gg .", "gg . neutrophils also", ". neutrophils also contain", "neutrophils also contain exocytosable", "also contain exocytosable storage", "contain exocytosable storage cell", "exocytosable storage cell organelles", "cell organelles storage", "organelles storage vesicles", "storage vesicles sv", "sv formed", "formed by endocytosis they", "by endocytosis they contain", "endocytosis they contain many", "they contain many cell", "contain many cell surface", "many cell surface markers", "cell surface markers and", "surface markers and extracellular", "and extracellular plasma", "extracellular plasma proteins", "plasma proteins borregaard", "proteins borregaard et", "borregaard et al. 1992", "et al. 1992 .", "al. 1992 . ficolin", "1992 . ficolin 1", ". ficolin 1 rich", "ficolin 1 rich granules", "rich granules fg", "fg are like", "are like ggs highly", "like ggs highly exocytosable", "ggs highly exocytosable but", "highly exocytosable but gelatinase", "exocytosable but gelatinase poor", "gelatinase poor rorvig", "poor rorvig et", "rorvig et al. 2009", "et al. 2009 .", "neutrophils are the most abundant", "are the most abundant leukocytes", "most abundant leukocytes white", "abundant leukocytes white blood", "leukocytes white blood cells", "blood cells indispensable", "cells indispensable in", "indispensable in defending the body", "in defending the body against", "defending the body against invading", "the body against invading microorganisms.", "body against invading microorganisms. in", "against invading microorganisms. in response", "invading microorganisms. in response to", "microorganisms. in response to infection", "response to infection neutrophils", "to infection neutrophils leave", "infection neutrophils leave the", "neutrophils leave the circulation and", "leave the circulation and migrate", "the circulation and migrate towards", "circulation and migrate towards the", "and migrate towards the inflammatory", "migrate towards the inflammatory focus.", "towards the inflammatory focus. they", "the inflammatory focus. they contain", "inflammatory focus. they contain several", "focus. they contain several subsets", "they contain several subsets of", "contain several subsets of granules", "several subsets of granules that", "subsets of granules that are", "of granules that are mobilized", "granules that are mobilized to", "that are mobilized to fuse", "are mobilized to fuse with", "mobilized to fuse with the", "to fuse with the cell", "fuse with the cell membrane", "with the cell membrane or", "the cell membrane or phagosomal", "cell membrane or phagosomal membrane", "or phagosomal membrane resulting", "phagosomal membrane resulting in", "membrane resulting in the", "resulting in the exocytosis or", "in the exocytosis or exposure", "the exocytosis or exposure of", "exocytosis or exposure of membrane", "or exposure of membrane proteins.", "exposure of membrane proteins. traditionally", "membrane proteins. traditionally neutrophil", "proteins. traditionally neutrophil granule", "traditionally neutrophil granule constituents", "neutrophil granule constituents are described", "granule constituents are described as", "constituents are described as antimicrobial", "are described as antimicrobial or", "described as antimicrobial or proteolytic", "antimicrobial or proteolytic but", "or proteolytic but granules", "proteolytic but granules also", "but granules also introduce membrane", "granules also introduce membrane proteins", "also introduce membrane proteins to", "introduce membrane proteins to the", "membrane proteins to the cell", "proteins to the cell surface", "the cell surface changing", "cell surface changing how", "surface changing how the", "changing how the neutrophil responds", "how the neutrophil responds to", "the neutrophil responds to its", "neutrophil responds to its environment", "to its environment borregaard", "its environment borregaard et", "environment borregaard et al.", "borregaard et al. 2007 .", "et al. 2007 . primed", "al. 2007 . primed neutrophils", "2007 . primed neutrophils actively", ". primed neutrophils actively secrete", "primed neutrophils actively secrete cytokines", "neutrophils actively secrete cytokines and", "actively secrete cytokines and other", "secrete cytokines and other inflammatory", "cytokines and other inflammatory mediators", "and other inflammatory mediators and", "other inflammatory mediators and can", "inflammatory mediators and can present", "mediators and can present antigens", "and can present antigens via", "can present antigens via mhc", "present antigens via mhc ii", "via mhc ii stimulating", "mhc ii stimulating t", "ii stimulating t cells", "stimulating t cells wright", "t cells wright et", "cells wright et al.", "wright et al. 2010 .

granules", "et al. 2010 .

granules form", "al. 2010 .

granules form during", "2010 .

granules form during neutrophil", ".

granules form during neutrophil differentiation.", "form during neutrophil differentiation. granule", "during neutrophil differentiation. granule subtypes", "neutrophil differentiation. granule subtypes can", "differentiation. granule subtypes can be", "granule subtypes can be distinguished", "subtypes can be distinguished by", "can be distinguished by their", "be distinguished by their content", "distinguished by their content but", "by their content but overlap", "their content but overlap in", "content but overlap in structure", "but overlap in structure and", "overlap in structure and composition.", "in structure and composition. the", "structure and composition. the differences", "and composition. the differences are", "composition. the differences are believed", "the differences are believed to", "differences are believed to be", "are believed to be a", "believed to be a consequence", "to be a consequence of", "be a consequence of changing", "a consequence of changing protein", "consequence of changing protein expression", "of changing protein expression and", "changing protein expression and differential", "protein expression and differential timing", "expression and differential timing of", "and differential timing of granule", "differential timing of granule formation", "timing of granule formation during", "of granule formation during the", "granule formation during the terminal", "formation during the terminal processes", "during the terminal processes of", "the terminal processes of neutrophil", "terminal processes of neutrophil differentiation", "of neutrophil differentiation rather", "neutrophil differentiation rather than", "differentiation rather than sorting", "rather than sorting le", "than sorting le cabec", "sorting le cabec et", "le cabec et al. 1996", "cabec et al. 1996 .", "et al. 1996 .
", "al. 1996 .

the", "1996 .

the classical", ".

the classical granule", "

the classical granule subsets", "
the classical granule subsets are", "classical granule subsets are azurophil", "granule subsets are azurophil or", "subsets are azurophil or primary", "are azurophil or primary granules", "or primary granules ag", "ag secondary granules", "granules sg and", "sg and gelatinase granules", "and gelatinase granules gg", "gelatinase granules gg .", "granules gg . neutrophils", "gg . neutrophils also contain", ". neutrophils also contain exocytosable", "neutrophils also contain exocytosable storage", "also contain exocytosable storage cell", "contain exocytosable storage cell organelles", "storage cell organelles storage", "cell organelles storage vesicles", "sv formed by", "formed by endocytosis they contain", "by endocytosis they contain many", "endocytosis they contain many cell", "they contain many cell surface", "contain many cell surface markers", "many cell surface markers and", "cell surface markers and extracellular", "markers and extracellular plasma", "and extracellular plasma proteins", "plasma proteins borregaard et", "proteins borregaard et al.", "borregaard et al. 1992 .", "et al. 1992 . ficolin", "al. 1992 . ficolin 1", "1992 . ficolin 1 rich", ". ficolin 1 rich granules", "1 rich granules fg", "granules fg are", "fg are like ggs", "are like ggs highly exocytosable", "like ggs highly exocytosable but", "ggs highly exocytosable but gelatinase", "highly exocytosable but gelatinase poor", "but gelatinase poor rorvig", "gelatinase poor rorvig et", "poor rorvig et al.", "rorvig et al. 2009 ." ] }, { "record_id": "GLY_000594_1_520", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6799198", "r hsa", "hsa 6799198", "r hsa 6799198" ] }, { "record_id": "GLY_000594_1_520", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "complex i", "i biogenesis", "complex i biogenesis", "nadh:ubiquinone oxidoreductase", "oxidoreductase or", "or nadh", "nadh dehydrogenase", "utilises 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transcriptional", "apoptotic pathway.

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transcriptional", "the apoptotic pathway.

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transcriptional activation of tp53aip1", "pathway.

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ep300 prmt1", "ep300 prmt1 and", "and carm1 an", "carm1 an et", "an et al. 2004", "et al. 2004 .", "al. 2004 . gadd45a", "2004 . gadd45a binds", ". gadd45a binds aurora", "gadd45a binds aurora kinase", "binds aurora kinase a", "kinase a aurka", "aurka inhibiting", "inhibiting its catalytic activity", "its catalytic activity and", "catalytic activity and preventing", "activity and preventing aurka", "and preventing aurka mediated", "preventing aurka mediated g2/m", "aurka mediated g2/m transition", "g2/m transition shao", "transition shao et", "shao et al. 2006", "al. 2006 sanchez", "2006 sanchez et", "sanchez et al. 2010", "et al. 2010 .", "al. 2010 . gadd45a", "2010 . gadd45a also", ". gadd45a also forms", "gadd45a also forms a", "also forms a complex", "forms a complex with", "a complex with pcna.", "complex with pcna. pcna", "with pcna. pcna is", "pcna. pcna is involved", "pcna is involved in", "is involved in both", "involved in both normal", "in both normal and", "both normal and repair", "normal and repair dna", "and repair dna synthesis.", "repair dna synthesis. the", "dna synthesis. the effect", "synthesis. the effect of", "the effect of gadd45", "effect of gadd45 interaction", "of gadd45 interaction with", "gadd45 interaction with pcna", "with pcna if", "pcna if any", "if any on", "any on s", "on s phase progression", "phase progression g2", "progression g2 arrest", "g2 arrest and dna", "arrest and dna repair", "and dna repair is", "dna repair is not", "repair is not known", "not known smith", "known smith et", "smith et al. 1994", "al. 1994 hall", "1994 hall et", "hall et al. 1995", "al. 1995 sanchez", "1995 sanchez et", "al. 2010 kim", "2010 kim et", "kim et al. 2013", "et al. 2013 .", "al. 2013 . sfn", ". sfn 14", "sfn 14 3", "14 3 3 sigma", "3 sigma is", "sigma is induced", "is induced by tp53", "by tp53 hermeking", "tp53 hermeking et", "hermeking et al. 1997", "al. 1997 and", "1997 and contributes", "and contributes to g2", "contributes to g2 arrest", "to g2 arrest by", "g2 arrest by binding", "arrest by binding to", "by binding to the", "binding to the complex", "to the complex of", "the complex of cdk1", "complex of cdk1 and", "of cdk1 and ccnb1", "and ccnb1 cyclin", "ccnb1 cyclin b1", "cyclin b1 and", "b1 and preventing", "and preventing its translocation", "preventing its translocation to", "its translocation to the", "translocation to the nucleus.", "to the nucleus. phosphorylation", "the nucleus. phosphorylation of", "nucleus. phosphorylation of a", "phosphorylation of a number", "of a number of", "a number of nuclear", "number of nuclear proteins", "of nuclear proteins by", "nuclear proteins by the", "proteins by the complex", "by the complex of", "cdk1 and ccnb1 is", "and ccnb1 is needed", "ccnb1 is needed for", "is needed for g2/m", "needed for g2/m transition", "g2/m transition chan", "transition chan et", "chan et al. 1999", "et al. 1999 .", "al. 1999 . while", "1999 . while promoting", ". while promoting g2", "while promoting g2 arrest", "g2 arrest sfn", "arrest sfn can", "sfn can simultaneously inhibit", "can simultaneously inhibit apoptosis", "simultaneously inhibit apoptosis by", "inhibit apoptosis by binding", "apoptosis by binding to", "by binding to bax", "binding to bax and", "to bax and preventing", "bax and preventing its", "its translocation to mitochondria", "to mitochondria a", "mitochondria a step", "a step involved in", "step involved in cytochrome", "involved in cytochrome c", "in cytochrome c release", "c release samuel", "release samuel et", "samuel et al. 2001", "et al. 2001 .", "al. 2001 . tp53", "2001 . tp53 binds", ". tp53 binds the", "tp53 binds the promoter", "binds the promoter of", "the promoter of the", "promoter of the cdc25c", "of the cdc25c gene", "the cdc25c gene in", "cdc25c gene in cooperation", "gene in cooperation with", "in cooperation with the", "cooperation with the transcriptional", "with the transcriptional repressor", "the transcriptional repressor e2f4", "transcriptional repressor e2f4 and", "repressor e2f4 and represses", "e2f4 and represses cdc25c", "and represses cdc25c transcription", "cdc25c transcription thus", "transcription thus maintaining", "thus maintaining g2 arrest", "g2 arrest st", "arrest st clair", "st clair et al.", "clair et al. 2004", "al. 2004 benson", "2004 benson et", "benson et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the zinc", ". the zinc finger", "the zinc finger transcription", "zinc finger transcription factor", "finger transcription factor znf385a", "factor znf385a hzf", "hzf is a", "is a direct transcriptional", "a direct transcriptional target", "direct transcriptional target of", "transcriptional target of tp53", "target of tp53 that", "of tp53 that can", "tp53 that can form", "that can form a", "can form a complex", "form a complex with", "a complex with tp53", "complex with tp53 and", "with tp53 and facilitate", "tp53 and facilitate tp53", "and facilitate tp53 mediated", "facilitate tp53 mediated induction", "tp53 mediated induction of", "mediated induction of sfn", "induction of sfn transcription", "sfn transcription das", "transcription das et", "das et al. 2007", "et al. 2007 .", "tp53 contributes to the establishment", "contributes to the establishment of", "to the establishment of g2", "the establishment of g2 arrest", "establishment of g2 arrest by", "of g2 arrest by inducing", "g2 arrest by inducing transcription", "arrest by inducing transcription of", "by inducing transcription of gadd45a", "inducing transcription of gadd45a and", "transcription of gadd45a and sfn", "gadd45a and sfn and", "and sfn and by", "sfn and by inhibiting", "and by inhibiting transcription of", "by inhibiting transcription of cdc25c.", "inhibiting transcription of cdc25c. tp53", "transcription of cdc25c. tp53 induces", "of cdc25c. tp53 induces gadd45a", "cdc25c. tp53 induces gadd45a transcription", "tp53 induces gadd45a transcription in", "induces gadd45a transcription in cooperation", "gadd45a transcription in cooperation with", "transcription in cooperation with chromatin", "in cooperation with chromatin modifying", "cooperation with chromatin modifying enzymes", "with chromatin modifying enzymes ep300", "modifying enzymes ep300 prmt1", "enzymes ep300 prmt1 and", "ep300 prmt1 and carm1", "prmt1 and carm1 an", "and carm1 an et", "carm1 an et al.", "an et al. 2004 .", "et al. 2004 . gadd45a", "al. 2004 . gadd45a binds", "2004 . gadd45a binds aurora", ". gadd45a binds aurora kinase", "gadd45a binds aurora kinase a", "aurora kinase a aurka", "aurka inhibiting its", "inhibiting its catalytic activity and", "its catalytic activity and preventing", "catalytic activity and preventing aurka", "activity and preventing aurka mediated", "and preventing aurka mediated g2/m", "preventing aurka mediated g2/m transition", "mediated g2/m transition shao", "g2/m transition shao et", "transition shao et al.", "et al. 2006 sanchez", "al. 2006 sanchez et", "2006 sanchez et al.", "sanchez et al. 2010 .", "et al. 2010 . gadd45a", "al. 2010 . gadd45a also", "2010 . gadd45a also forms", ". gadd45a also forms a", "gadd45a also forms a complex", "also forms a complex with", "forms a complex with pcna.", "a complex with pcna. pcna", "complex with pcna. pcna is", "with pcna. pcna is involved", "pcna. pcna is involved in", "pcna is involved in both", "is involved in both normal", "involved in both normal and", "in both normal and repair", "both normal and repair dna", "normal and repair dna synthesis.", "and repair dna synthesis. the", "repair dna synthesis. the effect", "dna synthesis. the effect of", "synthesis. the effect of gadd45", "the effect of gadd45 interaction", "effect of gadd45 interaction with", "of gadd45 interaction with pcna", "interaction with pcna if", "with pcna if any", "if any on s", "any on s phase", "s phase progression g2", "phase progression g2 arrest", "progression g2 arrest and", "g2 arrest and dna repair", "arrest and dna repair is", "and dna repair is not", "dna repair is not known", "is not known smith", "not known smith et", "known smith et al.", "et al. 1994 hall", "al. 1994 hall et", "1994 hall et al.", "et al. 1995 sanchez", "al. 1995 sanchez et", "1995 sanchez et al.", "et al. 2010 kim", "al. 2010 kim et", "2010 kim et al.", "kim et al. 2013 .", "et al. 2013 . sfn", "2013 . sfn 14", ". sfn 14 3", "sfn 14 3 3", "3 3 sigma is", "3 sigma is induced", "sigma is induced by", "induced by tp53 hermeking", "by tp53 hermeking et", "tp53 hermeking et al.", "et al. 1997 and", "al. 1997 and contributes", "1997 and contributes to", "and contributes to g2 arrest", "contributes to g2 arrest by", "to g2 arrest by binding", "g2 arrest by binding to", "arrest by binding to the", "by binding to the complex", "binding to the complex of", "to the complex of cdk1", "the complex of cdk1 and", "complex of cdk1 and ccnb1", "cdk1 and ccnb1 cyclin", "and ccnb1 cyclin b1", "cyclin b1 and preventing", "b1 and preventing its", "and preventing its translocation to", "preventing its translocation to the", "its translocation to the nucleus.", "translocation to the nucleus. phosphorylation", "to the nucleus. phosphorylation of", "the nucleus. phosphorylation of a", "nucleus. phosphorylation of a number", "phosphorylation of a number of", "of a number of nuclear", "a number of nuclear proteins", "number of nuclear proteins by", "of nuclear proteins by the", "nuclear proteins by the complex", "proteins by the complex of", "by the complex of cdk1", "of cdk1 and ccnb1 is", "cdk1 and ccnb1 is needed", "and ccnb1 is needed for", "ccnb1 is needed for g2/m", "is needed for g2/m transition", "for g2/m transition chan", "g2/m transition chan et", "transition chan et al.", "chan et al. 1999 .", "et al. 1999 . while", "al. 1999 . while promoting", "1999 . while promoting g2", ". while promoting g2 arrest", "promoting g2 arrest sfn", "g2 arrest sfn can", "arrest sfn can simultaneously", "sfn can simultaneously inhibit apoptosis", "can simultaneously inhibit apoptosis by", "simultaneously inhibit apoptosis by binding", "inhibit apoptosis by binding to", "apoptosis by binding to bax", "by binding to bax and", "binding to bax and preventing", "to bax and preventing its", "bax and preventing its translocation", "preventing its translocation to mitochondria", "translocation to mitochondria a", "to mitochondria a step", "mitochondria a step involved", "a step involved in cytochrome", "step involved in cytochrome c", "involved in cytochrome c release", "cytochrome c release samuel", "c release samuel et", "release samuel et al.", "samuel et al. 2001 .", "et al. 2001 . tp53", "al. 2001 . tp53 binds", "2001 . tp53 binds the", ". tp53 binds the promoter", "tp53 binds the promoter of", "binds the promoter of the", "the promoter of the cdc25c", "promoter of the cdc25c gene", "of the cdc25c gene in", "the cdc25c gene in cooperation", "cdc25c gene in cooperation with", "gene in cooperation with the", "in cooperation with the transcriptional", "cooperation with the transcriptional repressor", "with the transcriptional repressor e2f4", "the transcriptional repressor e2f4 and", "transcriptional repressor e2f4 and represses", "repressor e2f4 and represses cdc25c", "e2f4 and represses cdc25c transcription", "represses cdc25c transcription thus", "cdc25c transcription thus maintaining", "transcription thus maintaining g2", "maintaining g2 arrest st", "g2 arrest st clair", "arrest st clair et", "st clair et al. 2004", "et al. 2004 benson", "al. 2004 benson et", "2004 benson et al.", "benson et al. 2014 .", "et al. 2014 . the", "al. 2014 . the zinc", "2014 . the zinc finger", ". the zinc finger transcription", "the zinc finger transcription factor", "zinc finger transcription factor znf385a", "transcription factor znf385a hzf", "znf385a hzf is", "hzf is a direct", "is a direct transcriptional target", "a direct transcriptional target of", "direct transcriptional target of tp53", "transcriptional target of tp53 that", "target of tp53 that can", "of tp53 that can form", "tp53 that can form a", "that can form a complex", "can form a complex with", "form a complex with tp53", "a complex with tp53 and", "complex with tp53 and facilitate", "with tp53 and facilitate tp53", "tp53 and facilitate tp53 mediated", "and facilitate tp53 mediated induction", "facilitate tp53 mediated induction of", "tp53 mediated induction of sfn", "mediated induction of sfn transcription", "of sfn transcription das", "sfn transcription das et", "transcription das et al.", "das et al. 2007 ." ] }, { "record_id": "GLY_000594_1_528", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6804115", "r hsa", "hsa 6804115", "r hsa 6804115" ] }, { "record_id": "GLY_000594_1_528", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tp53 regulates", "regulates transcription", "transcription of", "of additional", "additional cell", "cell cycle", 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mechanism", "mechanism has", "has not", "not been", "been elucidated", "al. 1998", "mauxion et", "al. 2008", "horiuchi et", "al. 2009", "doidge et", "al. 2012", "ezzeddine et", "2012 .", ". two", "two polo", "polo like", "like kinases", "plk2 and", "and plk3", "are direct", "direct transcriptional", "transcriptional targets", "targets of", "of tp53.", "tp53. tp53", "tp53 mediated", "mediated induction", "induction of", "of plk2", "plk2 may", "may be", "be important", "important for", "for prevention", "prevention of", "of mitotic", "mitotic catastrophe", "catastrophe after", "after spindle", "spindle damage", "burns et", "al. 2003", "2003 .", ". plk2", "plk2 is", "is involved", "involved in", "the regulation", "regulation of", "of centrosome", "centrosome duplication", "duplication through", "through phosphorylation", "phosphorylation of", "centrosome related", "related proteins", "proteins cenpj", "chang et", "al. 2010", "and npm1", "krause and", "and hoffmann", "hoffmann 2010", "2010 .", "is frequently", "frequently transcriptionally", "transcriptionally silenced", "silenced through", "through promoter", "promoter methylation", "methylation in", "in b", "b cell", "cell malignancies", "syed et", "al. 2006", "2006 .", ". induction", "of plk3", "plk3 transcription", "transcription by", "jen and", "and cheung", "cheung 2005", "for coordination", "coordination of", "of m", "m phase", "phase events", "events through", "through plk3", "plk3 mediated", "mediated nuclear", "nuclear accumulation", "accumulation of", "of cdc25c", "bahassi et", "al. 2004", "2004 .", ". rgcc", "rgcc is", "tp53 and", "and implicated", "implicated in", "in cell", "cycle regulation", "possibly through", "through its", "its association", "association with", "with plk1", "saigusa et", "al. 2007", "2007 .", ". plagl1", "is a", "a zinc", "zinc finger", "finger protein", "protein directly", "directly transcriptionally", "transcriptionally induced", "rozenfeld granot", "granot et", "plagl1 expression", "expression is", "frequently lost", "lost in", "in cancer", "varrault et", "and plagl1", "plagl1 has", "has been", "been implicated", "in both", "both cell", "cycle arrest", "arrest and", "and apoptosis", "spengler et", "al. 1997", "but its", "its mechanism", "mechanism of", "of action", "action remains", "remains unknown.", "btg2 is induced", "is induced by", "induced by tp53", "tp53 leading", "leading to cessation", "to cessation of", "cessation of cellular", "of cellular proliferation", "proliferation rouault", "rouault et al.", "et al. 1996", "1996 duriez", "duriez et al.", "et al. 2002", "al. 2002 .", "2002 . btg2", ". btg2 binds", "btg2 binds to", "binds to the", "to the ccr4", "the ccr4 not", "ccr4 not complex", "not complex and", "complex and promotes", "and promotes mrna", "promotes mrna deadenylation", "mrna deadenylation activity", "deadenylation activity of", "activity of this", "of this complex.", "this complex. interaction", "complex. interaction between", "interaction between btg2", "between btg2 and", "btg2 and ccr4", "and ccr4 not", "ccr4 not is", "not is needed", "is needed for", "needed for the", "for the antiproliferative", "the antiproliferative activity", "antiproliferative activity of", "activity of btg2", "btg2 but", "but the underlying", "the underlying mechanism", "underlying mechanism has", "mechanism has not", "has not been", "not been elucidated", "elucidated rouault", "et al. 1998", "1998 mauxion", "mauxion et al.", "et al. 2008", "2008 horiuchi", "horiuchi et al.", "et al. 2009", "2009 doidge", "doidge et al.", "et al. 2012", "2012 ezzeddine", "ezzeddine et al.", "al. 2012 .", "2012 . two", ". two polo", "two polo like", "polo like kinases", "kinases plk2", "plk2 and plk3", "plk3 are", "are direct transcriptional", "direct transcriptional targets", "transcriptional targets of", "targets of tp53.", "of tp53. tp53", "tp53. tp53 mediated", "tp53 mediated induction", "mediated induction of", "induction of plk2", "of plk2 may", "plk2 may be", "may be important", "be important for", "important for prevention", "for prevention of", "prevention of mitotic", "of mitotic catastrophe", "mitotic catastrophe after", "catastrophe after spindle", "after spindle damage", "damage burns", "burns et al.", "et al. 2003", "al. 2003 .", "2003 . plk2", ". plk2 is", "plk2 is involved", "is involved in", "involved in the", "in the regulation", "the regulation of", "regulation of centrosome", "of centrosome duplication", "centrosome duplication through", "duplication through phosphorylation", "through phosphorylation of", "phosphorylation of centrosome", "of centrosome related", "centrosome related proteins", "related proteins cenpj", "cenpj chang", "chang et al.", "et al. 2010", "2010 and", "npm1 krause", "krause and hoffmann", "and hoffmann 2010", "hoffmann 2010 .", "2010 . plk2", "plk2 is frequently", "is frequently transcriptionally", "frequently transcriptionally silenced", "transcriptionally silenced through", "silenced through promoter", "through promoter methylation", "promoter methylation in", "methylation in b", "in b cell", "b cell malignancies", "malignancies syed", "syed et al.", "et al. 2006", "al. 2006 .", "2006 . induction", ". induction of", "induction of plk3", "of plk3 transcription", "plk3 transcription by", "transcription by tp53", "tp53 jen", "jen and cheung", "and cheung 2005", "2005 may", "important for coordination", "for coordination of", "coordination of m", "of m phase", "m phase events", "phase events through", "events through plk3", "through plk3 mediated", "plk3 mediated nuclear", "mediated nuclear accumulation", "nuclear accumulation of", "accumulation of cdc25c", "cdc25c bahassi", "bahassi et al.", "et al. 2004", "al. 2004 .", "2004 . rgcc", ". rgcc is", "rgcc is induced", "by tp53 and", "tp53 and implicated", "and implicated in", "implicated in cell", "in cell cycle", "cell cycle regulation", "regulation possibly", "possibly through its", "through its association", "its association with", "association with plk1", "plk1 saigusa", "saigusa et al.", "et al. 2007", "al. 2007 .", "2007 . plagl1", "plagl1 zac1", "zac1 is", "is a zinc", "a zinc finger", "zinc finger protein", "finger protein directly", "protein directly transcriptionally", "directly transcriptionally induced", "transcriptionally induced by", "tp53 rozenfeld", "rozenfeld granot et", "granot et al.", "2002 . plagl1", ". plagl1 expression", "plagl1 expression is", "expression is frequently", "is frequently lost", "frequently lost in", "lost in cancer", "cancer varrault", "varrault et al.", "1998 and", "and plagl1 has", "plagl1 has been", "has been implicated", "been implicated in", "implicated in both", "in both cell", "both cell cycle", "cell cycle arrest", "cycle arrest and", "arrest and apoptosis", "apoptosis spengler", "spengler et al.", "et al. 1997", "but its mechanism", "its mechanism of", "mechanism of action", "of action remains", "action remains unknown.", "btg2 is induced by", "is induced by tp53", "by tp53 leading", "tp53 leading to", "leading to cessation of", "to cessation of cellular", "cessation of cellular proliferation", "cellular proliferation rouault", "proliferation rouault et", "rouault et al. 1996", "al. 1996 duriez", "1996 duriez et", "duriez et al. 2002", "et al. 2002 .", "al. 2002 . btg2", "2002 . btg2 binds", ". btg2 binds to", "btg2 binds to the", "binds to the ccr4", "to the ccr4 not", "the ccr4 not complex", "ccr4 not complex and", "not complex and promotes", "complex and promotes mrna", "and promotes mrna deadenylation", "promotes mrna deadenylation activity", "mrna deadenylation activity of", "deadenylation activity of this", "activity of this complex.", "of this complex. interaction", "this complex. interaction between", "complex. interaction between btg2", "interaction between btg2 and", "between btg2 and ccr4", "btg2 and ccr4 not", "and ccr4 not is", "ccr4 not is needed", "not is needed for", "is needed for the", "needed for the antiproliferative", "for the antiproliferative activity", "the antiproliferative activity of", "antiproliferative activity of btg2", "of btg2 but", "btg2 but the", "but the underlying mechanism", "the underlying mechanism has", "underlying mechanism has not", "mechanism has not been", "has not been elucidated", "been elucidated rouault", "elucidated rouault et", "rouault et al. 1998", "al. 1998 mauxion", "1998 mauxion et", "mauxion et al. 2008", "al. 2008 horiuchi", "2008 horiuchi et", "horiuchi et al. 2009", "al. 2009 doidge", "2009 doidge et", "doidge et al. 2012", "al. 2012 ezzeddine", "2012 ezzeddine et", "ezzeddine et al. 2012", "et al. 2012 .", "al. 2012 . two", "2012 . two polo", ". two polo like", "two polo like kinases", "like kinases plk2", "kinases plk2 and", "and plk3 are", "plk3 are direct", "are direct transcriptional targets", "direct transcriptional targets of", "transcriptional targets of tp53.", "targets of tp53. tp53", "of tp53. tp53 mediated", "tp53. tp53 mediated induction", "tp53 mediated induction of", "mediated induction of plk2", "induction of plk2 may", "of plk2 may be", "plk2 may be important", "may be important for", "be important for prevention", "important for prevention of", "for prevention of mitotic", "prevention of mitotic catastrophe", "of mitotic catastrophe after", "mitotic catastrophe after spindle", "catastrophe after spindle damage", "spindle damage burns", "damage burns et", "burns et al. 2003", "et al. 2003 .", "al. 2003 . plk2", "2003 . plk2 is", ". plk2 is involved", "plk2 is involved in", "is involved in the", "involved in the regulation", "in the regulation of", "the regulation of centrosome", "regulation of centrosome duplication", "of centrosome duplication through", "centrosome duplication through phosphorylation", "duplication through phosphorylation of", "through phosphorylation of centrosome", "phosphorylation of centrosome related", "of centrosome related proteins", "centrosome related proteins cenpj", "proteins cenpj chang", "cenpj chang et", "chang et al. 2010", "al. 2010 and", "2010 and npm1", "and npm1 krause", "npm1 krause and", "krause and hoffmann 2010", "and hoffmann 2010 .", "hoffmann 2010 . plk2", "2010 . plk2 is", ". plk2 is frequently", "plk2 is frequently transcriptionally", "is frequently transcriptionally silenced", "frequently transcriptionally silenced through", "transcriptionally silenced through promoter", "silenced through promoter methylation", "through promoter methylation in", "promoter methylation in b", "methylation in b cell", "in b cell malignancies", "cell malignancies syed", "malignancies syed et", "syed et al. 2006", "et al. 2006 .", "al. 2006 . induction", "2006 . induction of", ". induction of plk3", "induction of plk3 transcription", "of plk3 transcription by", "plk3 transcription by tp53", "by tp53 jen", "tp53 jen and", "jen and cheung 2005", "cheung 2005 may", "2005 may be", "be important for coordination", "important for coordination of", "for coordination of m", "coordination of m phase", "of m phase events", "m phase events through", "phase events through plk3", "events through plk3 mediated", "through plk3 mediated nuclear", "plk3 mediated nuclear accumulation", "mediated nuclear accumulation of", "nuclear accumulation of cdc25c", "of cdc25c bahassi", "cdc25c bahassi et", "bahassi et al. 2004", "et al. 2004 .", "al. 2004 . rgcc", "2004 . rgcc is", ". rgcc is induced", "rgcc is induced by", "induced by tp53 and", "by tp53 and implicated", "tp53 and implicated in", "and implicated in cell", "implicated in cell cycle", "in cell cycle regulation", "cycle regulation possibly", "regulation possibly through", "possibly through its association", "through its association with", "its association with plk1", "with plk1 saigusa", "plk1 saigusa et", "saigusa et al. 2007", "et al. 2007 .", "al. 2007 . plagl1", ". plagl1 zac1", "zac1 is a", "is a zinc finger", "a zinc finger protein", "zinc finger protein directly", "finger protein directly transcriptionally", "protein directly transcriptionally induced", "directly transcriptionally induced by", "transcriptionally induced by tp53", "by tp53 rozenfeld", "tp53 rozenfeld granot", "rozenfeld granot et al.", "granot et al. 2002", "al. 2002 . plagl1", "2002 . plagl1 expression", ". plagl1 expression is", "plagl1 expression is frequently", "expression is frequently lost", "is frequently lost in", "frequently lost in cancer", "in cancer varrault", "cancer varrault et", "varrault et al. 1998", "al. 1998 and", "1998 and plagl1", "and plagl1 has been", "plagl1 has been implicated", "has been implicated in", "been implicated in both", "implicated in both cell", "in both cell cycle", "both cell cycle arrest", "cell cycle arrest and", "cycle arrest and apoptosis", "and apoptosis spengler", "apoptosis spengler et", "spengler et al. 1997", "1997 but", "but its mechanism of", "its mechanism of action", "mechanism of action remains", "of action remains unknown.", "btg2 is induced by tp53", "induced by tp53 leading", "by tp53 leading to", "tp53 leading to cessation", "leading to cessation of cellular", "to cessation of cellular proliferation", "of cellular proliferation rouault", "cellular proliferation rouault et", "proliferation rouault et al.", "et al. 1996 duriez", "al. 1996 duriez et", "1996 duriez et al.", "duriez et al. 2002 .", "et al. 2002 . btg2", "al. 2002 . btg2 binds", "2002 . btg2 binds to", ". btg2 binds to the", "btg2 binds to the ccr4", "binds to the ccr4 not", "to the ccr4 not complex", "the ccr4 not complex and", "ccr4 not complex and promotes", "not complex and promotes mrna", "complex and promotes mrna deadenylation", "and promotes mrna deadenylation activity", "promotes mrna deadenylation activity of", "mrna deadenylation activity of this", "deadenylation activity of this complex.", "activity of this complex. interaction", "of this complex. interaction between", "this complex. interaction between btg2", "complex. interaction between btg2 and", "interaction between btg2 and ccr4", "between btg2 and ccr4 not", "btg2 and ccr4 not is", "and ccr4 not is needed", "ccr4 not is needed for", "not is needed for the", "is needed for the antiproliferative", "needed for the antiproliferative activity", "for the antiproliferative activity of", "the antiproliferative activity of btg2", "activity of btg2 but", "of btg2 but the", "btg2 but the underlying", "but the underlying mechanism has", "the underlying mechanism has not", "underlying mechanism has not been", "mechanism has not been elucidated", "not been elucidated rouault", "been elucidated rouault et", "elucidated rouault et al.", "et al. 1998 mauxion", "al. 1998 mauxion et", "1998 mauxion et al.", "et al. 2008 horiuchi", "al. 2008 horiuchi et", "2008 horiuchi et al.", "et al. 2009 doidge", "al. 2009 doidge et", "2009 doidge et al.", "et al. 2012 ezzeddine", "al. 2012 ezzeddine et", "2012 ezzeddine et al.", "ezzeddine et al. 2012 .", "et al. 2012 . two", "al. 2012 . two polo", "2012 . two polo like", ". two polo like kinases", "polo like kinases plk2", "like kinases plk2 and", "kinases plk2 and plk3", "plk2 and plk3 are", "and plk3 are direct", "plk3 are direct transcriptional", "are direct transcriptional targets of", "direct transcriptional targets of tp53.", "transcriptional targets of tp53. tp53", "targets of tp53. tp53 mediated", "of tp53. tp53 mediated induction", "tp53. tp53 mediated induction of", "tp53 mediated induction of plk2", "mediated induction of plk2 may", "induction of plk2 may be", "of plk2 may be important", "plk2 may be important for", "may be important for prevention", "be important for prevention of", "important for prevention of mitotic", "for prevention of mitotic catastrophe", "prevention of mitotic catastrophe after", "of mitotic catastrophe after spindle", "mitotic catastrophe after spindle damage", "after spindle damage burns", "spindle damage burns et", "damage burns et al.", "burns et al. 2003 .", "et al. 2003 . plk2", "al. 2003 . plk2 is", "2003 . plk2 is involved", ". plk2 is involved in", "plk2 is involved in the", "is involved in the regulation", "involved in the regulation of", "in the regulation of centrosome", "the regulation of centrosome duplication", "regulation of centrosome duplication through", "of centrosome duplication through phosphorylation", "centrosome duplication through phosphorylation of", "duplication through phosphorylation of centrosome", "through phosphorylation of centrosome related", "phosphorylation of centrosome related proteins", "of centrosome related proteins cenpj", "related proteins cenpj chang", "proteins cenpj chang et", "cenpj chang et al.", "et al. 2010 and", "al. 2010 and npm1", "and npm1 krause and", "npm1 krause and hoffmann", "krause and hoffmann 2010 .", "and hoffmann 2010 . plk2", "hoffmann 2010 . plk2 is", "2010 . plk2 is frequently", ". plk2 is frequently transcriptionally", "plk2 is frequently transcriptionally silenced", "is frequently transcriptionally silenced through", "frequently transcriptionally silenced through promoter", "transcriptionally silenced through promoter methylation", "silenced through promoter methylation in", "through promoter methylation in b", "promoter methylation in b cell", "methylation in b cell malignancies", "b cell malignancies syed", "cell malignancies syed et", "malignancies syed et al.", "syed et al. 2006 .", "et al. 2006 . induction", "al. 2006 . induction of", "2006 . induction of plk3", ". induction of plk3 transcription", "induction of plk3 transcription by", "of plk3 transcription by tp53", "transcription by tp53 jen", "by tp53 jen and", "tp53 jen and cheung", "and cheung 2005 may", "cheung 2005 may be", "2005 may be important", "may be important for coordination", "be important for coordination of", "important for coordination of m", "for coordination of m phase", "coordination of m phase events", "of m phase events through", "m phase events through plk3", "phase events through plk3 mediated", "events through plk3 mediated nuclear", "through plk3 mediated nuclear accumulation", "plk3 mediated nuclear accumulation of", "mediated nuclear accumulation of cdc25c", "accumulation of cdc25c bahassi", "of cdc25c bahassi et", "cdc25c bahassi et al.", "bahassi et al. 2004 .", "et al. 2004 . rgcc", "al. 2004 . rgcc is", "2004 . rgcc is induced", ". rgcc is induced by", "rgcc is induced by tp53", "is induced by tp53 and", "induced by tp53 and implicated", "by tp53 and implicated in", "tp53 and implicated in cell", "and implicated in cell cycle", "implicated in cell cycle regulation", "cell cycle regulation possibly", "cycle regulation possibly through", "regulation possibly through its", "possibly through its association with", "through its association with plk1", "association with plk1 saigusa", "with plk1 saigusa et", "plk1 saigusa et al.", "saigusa et al. 2007 .", "et al. 2007 . plagl1", "2007 . plagl1 zac1", "plagl1 zac1 is", "zac1 is a zinc", "is a zinc finger protein", "a zinc finger protein directly", "zinc finger protein directly transcriptionally", "finger protein directly transcriptionally induced", "protein directly transcriptionally induced by", "directly transcriptionally induced by tp53", "induced by tp53 rozenfeld", "by tp53 rozenfeld granot", "tp53 rozenfeld granot et", "rozenfeld granot et al. 2002", "granot et al. 2002 .", "et al. 2002 . plagl1", "al. 2002 . plagl1 expression", "2002 . plagl1 expression is", ". plagl1 expression is frequently", "plagl1 expression is frequently lost", "expression is frequently lost in", "is frequently lost in cancer", "lost in cancer varrault", "in cancer varrault et", "cancer varrault et al.", "et al. 1998 and", "al. 1998 and plagl1", "1998 and plagl1 has", "and plagl1 has been implicated", "plagl1 has been implicated in", "has been implicated in both", "been implicated in both cell", "implicated in both cell cycle", "in both cell cycle arrest", "both cell cycle arrest and", "cell cycle arrest and apoptosis", "arrest and apoptosis spengler", "and apoptosis spengler et", "apoptosis spengler et al.", "al. 1997 but", "1997 but its", "but its mechanism of action", "its mechanism of action remains", "mechanism of action remains unknown." ] }, { "record_id": "GLY_000594_1_529", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6804116", "r hsa", "hsa 6804116", "r hsa 6804116" ] }, { "record_id": "GLY_000594_1_529", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tp53 regulates", "regulates transcription", "transcription of", "of genes", "genes involved", "involved in", "in g1", "g1 cell", "cell cycle", "cycle arrest", "tp53 regulates transcription", "regulates transcription of", "transcription of genes", "of genes involved", "genes involved in", "involved in g1", "in g1 cell", "g1 cell cycle", "cell cycle arrest", "tp53 regulates transcription of", "regulates transcription of genes", "transcription of genes 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"factor that", "that promotes", "promotes expression", "of many", "many genes", "genes needed", "needed for", "for g1/s", "aksoy et", "al. 2012", "carvajal et", "2012 .", ". arid3a", "arid3a is", "is a", "a direct", "direct transcriptional", "transcriptional target", "target of", "of tp53", "ma et", "al. 2003", "that may", "may promote", "promote g1", "by cooperating", "cooperating with", "with tp53", "tp53 in", "in induction", "induction of", "of cdkn1a", "cdkn1a transcription", "lestari et", ". however", "arid3a may", "may also", "also promote", "promote g1/s", "transition by", "by stimulating", "stimulating transcriptional", "transcriptional activity", "activity of", "suzuki et", "al. 1998", "peeper et", "al. 2002", "2002 .

tp53", ".

tp53 has", "has co", "co factors", "factors that", "that are", "are key", "key determinants", "determinants of", "of transcriptional", "transcriptional selectivity", "selectivity within", "within the", "the p53", "p53 network.", "network. for", "the zinc", "zinc finger", "finger transcription", "factor znf385a", "tp53 that", "that can", "can form", "form a", "a complex", "tp53 and", "and facilitate", "facilitate tp53", "tp53 mediated", "mediated induction", "strongly favouring", "favouring cell", "arrest over", "over apoptosis", "das et", "al. 2007", "2007 .", "the most prominent", "most prominent tp53", "prominent tp53 target", "tp53 target involved", "target involved in", "in g1 arrest", "g1 arrest is", "arrest is the", "is the inhibitor", "the inhibitor of", "inhibitor of cyclin", "of cyclin dependent", "cyclin dependent kinases", "dependent kinases cdkn1a", "cdkn1a p21", "p21 . cdkn1a", ". cdkn1a is", "cdkn1a is one", "is one of", "one of the", "of the earliest", "the earliest genes", "earliest genes induced", "genes induced by", "induced by tp53", "tp53 el", "el deiry et", "deiry et al.", "et al. 1993", "al. 1993 .", "1993 . cdkn1a", ". cdkn1a binds", "cdkn1a binds and", "binds and inactivates", "and inactivates cdk2", "inactivates cdk2 in", "cdk2 in complex", "in complex with", "complex with cyclin", "with cyclin a", "a ccna", "ccna or", "e ccne", "thus preventing g1/s", "preventing g1/s transition", "transition harper", "harper et al.", "1993 . considering", ". considering its", "considering its impact", "its impact on", "impact on the", "on the cell", "the cell cycle", "cell cycle outcome", "outcome cdkn1a", "cdkn1a expression levels", "expression levels are", "levels are tightly", "are tightly regulated.", "tightly regulated. for", "regulated. for instance", "instance under", "under prolonged stress", "stress tp53", "tp53 can induce", "can induce the", "induce the transcription", "the transcription of", "transcription of an", "of an rna", "an rna binding", "rna binding protein", "binding protein pcbp4", "pcbp4 which", "which can bind", "can bind and", "bind and destabilize", "and destabilize cdkn1a", "destabilize cdkn1a mrna", "mrna thus", "thus alleviating g1", "alleviating g1 arrest", "g1 arrest and", "arrest and directing", "and directing the", "directing the affected", "the affected cell", "affected cell towards", "cell towards g2", "towards g2 arrest", "g2 arrest and", "and possibly", "possibly apoptosis", "apoptosis zhu", "zhu and chen", "and chen 2000", "2000 scoumanne", "scoumanne et al.", "et al. 2011", "al. 2011 .", "2011 . expression", ". expression of", "expression of e2f7", "of e2f7 is", "e2f7 is directly", "is directly induced", "directly induced by", "induced by tp53.", "by tp53. e2f7", "tp53. e2f7 contributes", "e2f7 contributes to", "contributes to g1", "to g1 cell", "cycle arrest by", "arrest by repressing", "by repressing transcription", "repressing transcription of", "transcription of e2f1", "e2f1 a", "a transcription factor", "transcription factor that", "factor that promotes", "that promotes expression", "promotes expression of", "expression of many", "of many genes", "many genes needed", "genes needed for", "needed for g1/s", "for g1/s transition", "transition aksoy", "aksoy et al.", "et al. 2012", "2012 carvajal", "carvajal et al.", "al. 2012 .", "2012 . arid3a", ". arid3a is", "arid3a is a", "is a direct", "a direct transcriptional", "direct transcriptional target", "transcriptional target of", "target of tp53", "tp53 ma", "ma et al.", "et al. 2003", "2003 that", "that may promote", "may promote g1", "promote g1 arrest", "g1 arrest by", "arrest by cooperating", "by cooperating with", "cooperating with tp53", "with tp53 in", "tp53 in induction", "in induction of", "induction of cdkn1a", "of cdkn1a transcription", "transcription lestari", "lestari et al.", "2012 . however", "however arid3a", "arid3a may also", "may also promote", "also promote g1/s", "promote g1/s transition", "g1/s transition by", "transition by stimulating", "by stimulating transcriptional", "stimulating transcriptional activity", "transcriptional activity of", "activity of e2f1", "e2f1 suzuki", "suzuki et al.", "et al. 1998", "1998 peeper", "peeper et al.", "et al. 2002", "al. 2002 .

tp53", "2002 .

tp53 has", ".

tp53 has co", "has co factors", "co factors that", "factors that are", "that are key", "are key determinants", "key determinants of", "determinants of transcriptional", "of transcriptional selectivity", "transcriptional selectivity within", "selectivity within the", "within the p53", "the p53 network.", "p53 network. for", "network. for instance", "instance the", "the zinc finger", "zinc finger transcription", "finger transcription factor", "transcription factor znf385a", "znf385a hzf", "hzf is", "of tp53 that", "tp53 that can", "that can form", "can form a", "form a complex", "a complex with", "complex with tp53", "with tp53 and", "tp53 and facilitate", "and facilitate tp53", "facilitate tp53 mediated", "tp53 mediated induction", "mediated induction of", "cdkn1a strongly", "strongly favouring cell", "favouring cell cycle", "cycle arrest over", "arrest over apoptosis", "apoptosis das", "das et al.", "et al. 2007", "al. 2007 .", "the most prominent tp53", "most prominent tp53 target", "prominent tp53 target involved", "tp53 target involved in", "target involved in g1", "involved in g1 arrest", "in g1 arrest is", "g1 arrest is the", "arrest is the inhibitor", "is the inhibitor of", "the inhibitor of cyclin", "inhibitor of cyclin dependent", "of cyclin dependent kinases", "cyclin dependent kinases cdkn1a", "kinases cdkn1a p21", "cdkn1a p21 .", "p21 . cdkn1a is", ". cdkn1a is one", "cdkn1a is one of", "is one of the", "one of the earliest", "of the earliest genes", "the earliest genes induced", "earliest genes induced by", "genes induced by tp53", "by tp53 el", "tp53 el deiry", "el deiry et al.", "deiry et al. 1993", "et al. 1993 .", "al. 1993 . cdkn1a", "1993 . cdkn1a binds", ". cdkn1a binds and", "cdkn1a binds and inactivates", "binds and inactivates cdk2", "and inactivates cdk2 in", "inactivates cdk2 in complex", "cdk2 in complex with", "in complex with cyclin", "complex with cyclin a", "cyclin a ccna", "ccna or e", "or e ccne", "ccne thus", "thus preventing g1/s transition", "g1/s transition harper", "transition harper et", "harper et al. 1993", "al. 1993 . considering", "1993 . considering its", ". considering its impact", "considering its impact on", "its impact on the", "impact on the cell", "on the cell cycle", "the cell cycle outcome", "cycle outcome cdkn1a", "outcome cdkn1a expression", "cdkn1a expression levels are", "expression levels are tightly", "levels are tightly regulated.", "are tightly regulated. for", "tightly regulated. for instance", "for instance under", "instance under prolonged", "prolonged stress tp53", "stress tp53 can", "tp53 can induce the", "can induce the transcription", "induce the transcription of", "the transcription of an", "transcription of an rna", "of an rna binding", "an rna binding protein", "rna binding protein pcbp4", "protein pcbp4 which", "pcbp4 which can", "which can bind and", "can bind and destabilize", "bind and destabilize cdkn1a", "and destabilize cdkn1a mrna", "cdkn1a mrna thus", "mrna thus alleviating", "thus alleviating g1 arrest", "alleviating g1 arrest and", "g1 arrest and directing", "arrest and directing the", "and directing the affected", "directing the affected cell", "the affected cell towards", "affected cell towards g2", "cell towards g2 arrest", "towards g2 arrest and", "arrest and possibly", "apoptosis zhu and", "zhu and chen 2000", "chen 2000 scoumanne", "2000 scoumanne et", "scoumanne et al. 2011", "et al. 2011 .", "al. 2011 . expression", "2011 . expression of", ". expression of e2f7", "expression of e2f7 is", "of e2f7 is directly", "e2f7 is directly induced", "is directly induced by", "directly induced by tp53.", "induced by tp53. e2f7", "by tp53. e2f7 contributes", "tp53. e2f7 contributes to", "e2f7 contributes to g1", "contributes to g1 cell", "to g1 cell cycle", "cell cycle arrest by", "cycle arrest by repressing", "arrest by repressing transcription", "by repressing transcription of", "repressing transcription of e2f1", "of e2f1 a", "e2f1 a transcription", "a transcription factor that", "transcription factor that promotes", "factor that promotes expression", "that promotes expression of", "promotes expression of many", "expression of many genes", "of many genes needed", "many genes needed for", "genes needed for g1/s", "needed for g1/s transition", "g1/s transition aksoy", "transition aksoy et", "aksoy et al. 2012", "al. 2012 carvajal", "2012 carvajal et", "carvajal et al. 2012", "et al. 2012 .", "al. 2012 . arid3a", "2012 . arid3a is", ". arid3a is a", "arid3a is a direct", "is a direct transcriptional", "a direct transcriptional target", "direct transcriptional target of", "transcriptional target of tp53", "of tp53 ma", "tp53 ma et", "ma et al. 2003", "al. 2003 that", "2003 that may", "that may promote g1", "may promote g1 arrest", "promote g1 arrest by", "g1 arrest by cooperating", "arrest by cooperating with", "by cooperating with tp53", "cooperating with tp53 in", "with tp53 in induction", "tp53 in induction of", "in induction of cdkn1a", "induction of cdkn1a transcription", "cdkn1a transcription lestari", "transcription lestari et", "lestari et al. 2012", "al. 2012 . however", ". however arid3a", "however arid3a may", "arid3a may also promote", "may also promote g1/s", "also promote g1/s transition", "promote g1/s transition by", "g1/s transition by stimulating", "transition by stimulating transcriptional", "by stimulating transcriptional activity", "stimulating transcriptional activity of", "transcriptional activity of e2f1", "of e2f1 suzuki", "e2f1 suzuki et", "suzuki et al. 1998", "al. 1998 peeper", "1998 peeper et", "peeper et al. 2002", "et al. 2002 .

tp53", "al. 2002 .

tp53 has", "2002 .

tp53 has co", ".

tp53 has co factors", "has co factors that", "co factors that are", "factors that are key", "that are key determinants", "are key determinants of", "key determinants of transcriptional", "determinants of transcriptional selectivity", "of transcriptional selectivity within", "transcriptional selectivity within the", "selectivity within the p53", "within the p53 network.", "the p53 network. for", "p53 network. for instance", "for instance the", "instance the zinc", "the zinc finger transcription", "zinc finger transcription factor", "finger transcription factor znf385a", "factor znf385a hzf", "hzf is a", "target of tp53 that", "of tp53 that can", "tp53 that can form", "that can form a", "can form a complex", "form a complex with", "a complex with tp53", "complex with tp53 and", "with tp53 and facilitate", "tp53 and facilitate tp53", "and facilitate tp53 mediated", "facilitate tp53 mediated induction", "tp53 mediated induction of", "mediated induction of cdkn1a", "of cdkn1a strongly", "cdkn1a strongly favouring", "strongly favouring cell cycle", "favouring cell cycle arrest", "cell cycle arrest over", "cycle arrest over apoptosis", "over apoptosis das", "apoptosis das et", "das et al. 2007", "et al. 2007 .", "the most prominent tp53 target", "most prominent tp53 target involved", "prominent tp53 target involved in", "tp53 target involved in g1", "target involved in g1 arrest", "involved in g1 arrest is", "in g1 arrest is the", "g1 arrest is the inhibitor", "arrest is the inhibitor of", "is the inhibitor of cyclin", "the inhibitor of cyclin dependent", "inhibitor of cyclin dependent kinases", "of cyclin dependent kinases cdkn1a", "dependent kinases cdkn1a p21", "kinases cdkn1a p21 .", "cdkn1a p21 . cdkn1a", "p21 . cdkn1a is one", ". cdkn1a is one of", "cdkn1a is one of the", "is one of the earliest", "one of the earliest genes", "of the earliest genes induced", "the earliest genes induced by", "earliest genes induced by tp53", "induced by tp53 el", "by tp53 el deiry", "tp53 el deiry et", "el deiry et al. 1993", "deiry et al. 1993 .", "et al. 1993 . cdkn1a", "al. 1993 . cdkn1a binds", "1993 . cdkn1a binds and", ". cdkn1a binds and inactivates", "cdkn1a binds and inactivates cdk2", "binds and inactivates cdk2 in", "and inactivates cdk2 in complex", "inactivates cdk2 in complex with", "cdk2 in complex with cyclin", "in complex with cyclin a", "with cyclin a ccna", "a ccna or", "ccne thus preventing", "preventing g1/s transition harper", "g1/s transition harper et", "transition harper et al.", "harper et al. 1993 .", "et al. 1993 . considering", "al. 1993 . considering its", "1993 . considering its impact", ". considering its impact on", "considering its impact on the", "its impact on the cell", "impact on the cell cycle", "on the cell cycle outcome", "cell cycle outcome cdkn1a", "cycle outcome cdkn1a expression", "outcome cdkn1a expression levels", "cdkn1a expression levels are tightly", "expression levels are tightly regulated.", "levels are tightly regulated. for", "are tightly regulated. for instance", "regulated. for instance under", "for instance under prolonged", "instance under prolonged stress", "under prolonged stress tp53", "prolonged stress tp53 can", "stress tp53 can induce", "tp53 can induce the transcription", "can induce the transcription of", "induce the transcription of an", "the transcription of an rna", "transcription of an rna binding", "of an rna binding protein", "an rna binding protein pcbp4", "binding protein pcbp4 which", "protein pcbp4 which can", "pcbp4 which can bind", "which can bind and destabilize", "can bind and destabilize cdkn1a", "bind and destabilize cdkn1a mrna", "destabilize cdkn1a mrna thus", "cdkn1a mrna thus alleviating", "mrna thus alleviating g1", "thus alleviating g1 arrest and", "alleviating g1 arrest and directing", "g1 arrest and directing the", "arrest and directing the affected", "and directing the affected cell", "directing the affected cell towards", "the affected cell towards g2", "affected cell towards g2 arrest", "cell towards g2 arrest and", "g2 arrest and possibly", "and possibly apoptosis", "possibly apoptosis zhu", "apoptosis zhu and chen", "and chen 2000 scoumanne", "chen 2000 scoumanne et", "2000 scoumanne et al.", "scoumanne et al. 2011 .", "et al. 2011 . expression", "al. 2011 . expression of", "2011 . expression of e2f7", ". expression of e2f7 is", "expression of e2f7 is directly", "of e2f7 is directly induced", "e2f7 is directly induced by", "is directly induced by tp53.", "directly induced by tp53. e2f7", "induced by tp53. e2f7 contributes", "by tp53. e2f7 contributes to", "tp53. e2f7 contributes to g1", "e2f7 contributes to g1 cell", "contributes to g1 cell cycle", "to g1 cell cycle arrest", "g1 cell cycle arrest by", "cell cycle arrest by repressing", "cycle arrest by repressing transcription", "arrest by repressing transcription of", "by repressing transcription of e2f1", "transcription of e2f1 a", "of e2f1 a transcription", "e2f1 a transcription factor", "a transcription factor that promotes", "transcription factor that promotes expression", "factor that promotes expression of", "that promotes expression of many", "promotes expression of many genes", "expression of many genes needed", "of many genes needed for", "many genes needed for g1/s", "genes needed for g1/s transition", "for g1/s transition aksoy", "g1/s transition aksoy et", "transition aksoy et al.", "et al. 2012 carvajal", "al. 2012 carvajal et", "2012 carvajal et al.", "carvajal et al. 2012 .", "et al. 2012 . arid3a", "al. 2012 . arid3a is", "2012 . arid3a is a", ". arid3a is a direct", "arid3a is a direct transcriptional", "is a direct transcriptional target", "a direct transcriptional target of", "direct transcriptional target of tp53", "target of tp53 ma", "of tp53 ma et", "tp53 ma et al.", "et al. 2003 that", "al. 2003 that may", "2003 that may promote", "that may promote g1 arrest", "may promote g1 arrest by", "promote g1 arrest by cooperating", "g1 arrest by cooperating with", "arrest by cooperating with tp53", "by cooperating with tp53 in", "cooperating with tp53 in induction", "with tp53 in induction of", "tp53 in induction of cdkn1a", "in induction of cdkn1a transcription", "of cdkn1a transcription lestari", "cdkn1a transcription lestari et", "transcription lestari et al.", "lestari et al. 2012 .", "et al. 2012 . however", "2012 . however arid3a", ". however arid3a may", "however arid3a may also", "arid3a may also promote g1/s", "may also promote g1/s transition", "also promote g1/s transition by", "promote g1/s transition by stimulating", "g1/s transition by stimulating transcriptional", "transition by stimulating transcriptional activity", "by stimulating transcriptional activity of", "stimulating transcriptional activity of e2f1", "activity of e2f1 suzuki", "of e2f1 suzuki et", "e2f1 suzuki et al.", "et al. 1998 peeper", "al. 1998 peeper et", "1998 peeper et al.", "peeper et al. 2002 .

tp53", "et al. 2002 .

tp53 has", "al. 2002 .

tp53 has co", "2002 .

tp53 has co factors", ".

tp53 has co factors that", "has co factors that are", "co factors that are key", "factors that are key determinants", "that are key determinants of", "are key determinants of transcriptional", "key determinants of transcriptional selectivity", "determinants of transcriptional selectivity within", "of transcriptional selectivity within the", "transcriptional selectivity within the p53", "selectivity within the p53 network.", "within the p53 network. for", "the p53 network. for instance", "network. for instance the", "for instance the zinc", "instance the zinc finger", "the zinc finger transcription factor", "zinc finger transcription factor znf385a", "transcription factor znf385a hzf", "znf385a hzf is", "hzf is a direct", "transcriptional target of tp53 that", "target of tp53 that can", "of tp53 that can form", "tp53 that can form a", "that can form a complex", "can form a complex with", "form a complex with tp53", "a complex with tp53 and", "complex with tp53 and facilitate", "with tp53 and facilitate tp53", "tp53 and facilitate tp53 mediated", "and facilitate tp53 mediated induction", "facilitate tp53 mediated induction of", "tp53 mediated induction of cdkn1a", "induction of cdkn1a strongly", "of cdkn1a strongly favouring", "cdkn1a strongly favouring cell", "strongly favouring cell cycle arrest", "favouring cell cycle arrest over", "cell cycle arrest over apoptosis", "arrest over apoptosis das", "over apoptosis das et", "apoptosis das et al.", "das et al. 2007 ." ] }, { "record_id": "GLY_000594_1_530", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6804756", "r hsa", "hsa 6804756", "r hsa 6804756" ] }, { "record_id": "GLY_000594_1_530", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of tp53", "tp53 activity", "activity through", "through phosphorylation", "regulation of tp53", "of tp53 activity", "tp53 activity through", "activity through phosphorylation", "regulation of tp53 activity", "of tp53 activity through", "tp53 activity through phosphorylation", "regulation of tp53 activity through", "of tp53 activity through phosphorylation", "phosphorylation of", "at the", "the n", "n terminal", "terminal serine", "serine residues", "residues s15", "s15 and", "and s20", "s20 plays", "plays a", "a critical", "critical role", "role in", "in protein", "protein stabilization", "stabilization as", "as phosphorylation", "phosphorylation at", "at these", "these sites", "sites interferes", "interferes with", "with binding", "binding of", "of the", "the ubiquitin", "ubiquitin ligase", "ligase mdm2", "mdm2 to", "to tp53.", "tp53. several", "several different", "different kinases", "kinases can", "can phosphorylate", "phosphorylate tp53", "tp53 at", "at s15", "and s20.", "s20. in", "in response", "response to", "to double", "double strand", "strand dna", "dna breaks", "s15 is", "is phosphorylated", "phosphorylated by", "by atm", "banin et", "et al.", "al. 1998", "canman et", "khanna et", "s20 by", "by chek2", "chehab et", "al. 1999", "al. 2000", "hirao et", "2000 .", ". dna", "dna damage", "damage or", "or other", "other types", "types of", "of genotoxic", "genotoxic stress", "such as", "as stalled", "stalled replication", "replication forks", "can trigger", "trigger atr", "atr mediated", "mediated phosphorylation", "lakin et", "tibbetts et", "and chek1", "chek1 mediated", "at s20", "shieh et", ". in", "to various", "various types", "of cell", "cell stress", "hou et", "al. 2011", "zhang et", "al. 2002", "lee et", "al. 2007", "al. 2008", "jones et", "al. 2005", "and tp53rk", "abe et", "al. 2001", "facchin et", "al. 2003", "while plk3", "wang et", "wu et", "at s20.

phosphorylation", "s20.

phosphorylation of", "at serine", "serine residue", "residue s46", "s46 promotes", "promotes transcription", "transcription of", "tp53 regulated", "regulated apoptotic", "apoptotic genes", "genes rather", "rather than", "than cell", "cell cycle", "cycle arrest", "arrest genes.", "genes. several", "several kinases", "phosphorylate s46", "s46 of", "including atm", "atm activated", "activated dyrk2", "like tp53", "is targeted", "targeted for", "for degradation", "degradation by", "by mdm2", "taira et", "al. 2010", "2010 .", ". tp53", "tp53 is", "is also", "also phosphorylated", "phosphorylated at", "at s46", "s46 by", "by hipk2", "hipk2 in", "in the", "the presence", "presence of", "the tp53", "tp53 transcriptional", "transcriptional target", "target tp53inp1", "d'orazi et", "hofmann et", "tomasini et", "2003 .", ". cdk5", "in addition", "addition to", "to phosphorylating", "phosphorylating tp53", "also phosphorylates", "phosphorylates it", "it at", "at s33", "s33 and", "and s46", "which promotes", "promotes neuronal", "neuronal cell", "cell death", "2007 .

mapkapk5", "phosphorylates tp53", "residue s37", "promoting cell", "arrest and", "and cellular", "cellular senescence", "senescence in", "to oncogenic", "oncogenic ras", "ras signaling", "sun et", "2007 .

nuak1", ".

nuak1 phosphorylates", "and s392", "and phosphorylation", "at s392", "s392 may", "may contribute", "contribute to", "to tp53", "tp53 mediated", "mediated transcriptional", "transcriptional activation", "activation of", "arrest genes", "2011 .", ". s392", "s392 of", "by the", "the complex", "complex of", "of casein", "casein kinase", "kinase ii", "bound to", "to the", "the fact", "fact complex", "enhancing transcriptional", "transcriptional activity", "activity of", "tp53 in", "to uv", "uv irradiation", "keller et", "keller and", "and lu", "lu 2002", "2002 .

the", ".

the activity", "is inhibited", "inhibited by", "by phosphorylation", "residue s315", "which enhances", "enhances mdm2", "mdm2 binding", "binding and", "and degradation", "degradation of", "of tp53.", "tp53. s315", "s315 of", "by aurora", "aurora kinase", "kinase a", "katayama et", "al. 2004", "and cdk2", "luciani et", ". interaction", "interaction with", "with mdm2", "mdm2 and", "and the", "the consequent", "consequent tp53", "tp53 degradation", "degradation is", "also increased", "increased by", "tp53 threonine", "threonine residue", "residue t55", "t55 by", "the transcription", "transcription initiation", "initiation factor", "factor complex", "complex tfiid", "li et", "2004 .

aurora", ".

aurora kinase", "kinase b", "has been", "been shown", "shown to", "to phosphorylate", "residue s269", "s269 and", "and threonine", "residue t284", "which is", "is possibly", "possibly facilitated", "facilitated by", "the binding", "the nir", "nir co", "co repressor.", "repressor. aurkb", "aurkb mediated", "phosphorylation was", "was reported", "reported to", "to inhibit", "inhibit tp53", "through an", "an unknown", "unknown mechanism", ". a", "a putative", "putative direct", "direct interaction", "interaction between", "between tp53", "tp53 and", "and aurkb", "aurkb has", "has also", "also been", "been described", "described and", "and linked", "linked to", "tp53 phosphorylation", "phosphorylation and", "and s183", "t211 and", "and s215", "s215 and", "and tp53", "gully et", "al. 2012", "2012 .", "phosphorylation of tp53", "tp53 p53", "p53 at", "at the n", "the n terminal", "n terminal serine", "terminal serine residues", "serine residues s15", "residues s15 and", "s15 and s20", "and s20 plays", "s20 plays a", "plays a critical", "a critical role", "critical role in", "role in protein", "in protein stabilization", "protein stabilization as", "stabilization as phosphorylation", "as phosphorylation at", "phosphorylation at these", "at these sites", "these sites interferes", "sites interferes with", "interferes with binding", "with binding of", "binding of the", "of the ubiquitin", "the ubiquitin ligase", "ubiquitin ligase mdm2", "ligase mdm2 to", "mdm2 to tp53.", "to tp53. several", "tp53. several different", "several different kinases", "different kinases can", "kinases can phosphorylate", "can phosphorylate tp53", "phosphorylate tp53 at", "tp53 at s15", "at s15 and", "s15 and s20.", "and s20. in", "s20. in response", "in response to", "response to double", "to double strand", "double strand dna", "strand dna breaks", "breaks s15", "s15 is phosphorylated", "is phosphorylated by", "phosphorylated by atm", "atm banin", "banin et al.", "et al. 1998", "1998 canman", "canman et al.", "1998 khanna", "khanna et al.", "and s20 by", "s20 by chek2", "chek2 chehab", "chehab et al.", "et al. 1999", "1999 chehab", "et al. 2000", "2000 hirao", "hirao et al.", "al. 2000 .", "2000 . dna", ". dna damage", "dna damage or", "damage or other", "or other types", "other types of", "types of genotoxic", "of genotoxic stress", "stress such", "such as stalled", "as stalled replication", "stalled replication forks", "forks can", "can trigger atr", "trigger atr mediated", "atr mediated phosphorylation", "mediated phosphorylation of", "of tp53 at", "s15 lakin", "lakin et al.", "1999 tibbetts", "tibbetts et al.", "1999 and", "and chek1 mediated", "chek1 mediated phosphorylation", "tp53 at s20", "s20 shieh", "shieh et al.", "2000 . in", ". in response", "response to various", "to various types", "various types of", "types of cell", "of cell stress", "stress nuak1", "nuak1 hou", "hou et al.", "et al. 2011", "cdk5 zhang", "zhang et al.", "et al. 2002", "2002 lee", "lee et al.", "et al. 2007", "2007 lee", "et al. 2008", "ampk jones", "jones et al.", "et al. 2005", "2005 and", "tp53rk abe", "abe et al.", "et al. 2001", "2001 facchin", "facchin et al.", "et al. 2003", "2003 can", "s15 while", "plk3 xie", "xie wang", "wang et al.", "2001 xie", "xie wu", "wu et al.", "2001 can", "tp53 at s20.

phosphorylation", "at s20.

phosphorylation of", "s20.

phosphorylation of tp53", "tp53 at serine", "at serine residue", "serine residue s46", "residue s46 promotes", "s46 promotes transcription", "promotes transcription of", "transcription of tp53", "of tp53 regulated", "tp53 regulated apoptotic", "regulated apoptotic genes", "apoptotic genes rather", "genes rather than", "rather than cell", "than cell cycle", "cell cycle arrest", "cycle arrest genes.", "arrest genes. several", "genes. several kinases", "several kinases can", "can phosphorylate s46", "phosphorylate s46 of", "s46 of tp53", "tp53 including", "including atm activated", "atm activated dyrk2", "dyrk2 which", "which like", "is targeted for", "targeted for degradation", "for degradation by", "degradation by mdm2", "mdm2 taira", "taira et al.", "2007 taira", "et al. 2010", "al. 2010 .", "2010 . tp53", ". tp53 is", "tp53 is also", "is also phosphorylated", "also phosphorylated at", "phosphorylated at s46", "at s46 by", "s46 by hipk2", "by hipk2 in", "hipk2 in the", "in the presence", "the presence of", "presence of the", "of the tp53", "the tp53 transcriptional", "tp53 transcriptional target", "transcriptional target tp53inp1", "tp53inp1 d'orazi", "d'orazi et al.", "2002 hofmann", "hofmann et al.", "2002 tomasini", "tomasini et al.", "al. 2003 .", "2003 . cdk5", "cdk5 in", "in addition to", "addition to phosphorylating", "to phosphorylating tp53", "phosphorylating tp53 at", "s15 also", "also phosphorylates it", "phosphorylates it at", "it at s33", "at s33 and", "s33 and s46", "s46 which", "which promotes neuronal", "promotes neuronal cell", "neuronal cell death", "death lee", "al. 2007 .

mapkapk5", ".

mapkapk5 prak", "prak phosphorylates", "phosphorylates tp53 at", "serine residue s37", "s37 promoting", "promoting cell cycle", "cycle arrest and", "arrest and cellular", "and cellular senescence", "cellular senescence in", "senescence in response", "response to oncogenic", "to oncogenic ras", "oncogenic ras signaling", "signaling sun", "sun et al.", "al. 2007 .

nuak1", "2007 .

nuak1 phosphorylates", ".

nuak1 phosphorylates tp53", "s15 and s392", "s392 and", "and phosphorylation at", "phosphorylation at s392", "at s392 may", "s392 may contribute", "may contribute to", "contribute to tp53", "to tp53 mediated", "tp53 mediated transcriptional", "mediated transcriptional activation", "transcriptional activation of", "activation of cell", "of cell cycle", "cycle arrest genes", "genes hou", "al. 2011 .", "2011 . s392", ". s392 of", "s392 of tp53", "of tp53 is", "also phosphorylated by", "phosphorylated by the", "by the complex", "the complex of", "complex of casein", "of casein kinase", "casein kinase ii", "ii ck2", "ck2 bound", "bound to the", "to the fact", "the fact complex", "complex enhancing", "enhancing transcriptional activity", "transcriptional activity of", "activity of tp53", "of tp53 in", "tp53 in response", "response to uv", "to uv irradiation", "irradiation keller", "keller et al.", "2001 keller", "keller and lu", "and lu 2002", "lu 2002 .

the", "2002 .

the activity", ".

the activity of", "tp53 is inhibited", "is inhibited by", "inhibited by phosphorylation", "by phosphorylation at", "phosphorylation at serine", "serine residue s315", "s315 which", "which enhances mdm2", "enhances mdm2 binding", "mdm2 binding and", "binding and degradation", "and degradation of", "degradation of tp53.", "of tp53. s315", "tp53. s315 of", "s315 of tp53", "tp53 is phosphorylated", "phosphorylated by aurora", "by aurora kinase", "aurora kinase a", "a aurka", "katayama et al.", "et al. 2004", "2004 and", "cdk2 luciani", "luciani et al.", "2000 . interaction", ". interaction with", "interaction with mdm2", "with mdm2 and", "mdm2 and the", "and the consequent", "the consequent tp53", "consequent tp53 degradation", "tp53 degradation is", "degradation is also", "is also increased", "also increased by", "increased by phosphorylation", "by phosphorylation of", "of tp53 threonine", "tp53 threonine residue", "threonine residue t55", "residue t55 by", "t55 by the", "by the transcription", "the transcription initiation", "transcription initiation factor", "initiation factor complex", "factor complex tfiid", "tfiid li", "li et al.", "al. 2004 .

aurora", "2004 .

aurora kinase", ".

aurora kinase b", "b aurkb", "has been shown", "been shown to", "shown to phosphorylate", "to phosphorylate tp53", "serine residue s269", "residue s269 and", "s269 and threonine", "and threonine residue", "threonine residue t284", "t284 which", "which is possibly", "is possibly facilitated", "possibly facilitated by", "facilitated by the", "by the binding", "the binding of", "of the nir", "the nir co", "nir co repressor.", "co repressor. aurkb", "repressor. aurkb mediated", "aurkb mediated phosphorylation", "mediated phosphorylation was", "phosphorylation was reported", "was reported to", "reported to inhibit", "to inhibit tp53", "inhibit tp53 transcriptional", "tp53 transcriptional activity", "transcriptional activity through", "activity through an", "through an unknown", "an unknown mechanism", "mechanism wu", "2011 . a", ". a putative", "a putative direct", "putative direct interaction", "direct interaction between", "interaction between tp53", "between tp53 and", "tp53 and aurkb", "and aurkb has", "aurkb has also", "has also been", "also been described", "been described and", "described and linked", "and linked to", "linked to tp53", "to tp53 phosphorylation", "tp53 phosphorylation and", "phosphorylation and s183", "s183 t211", "t211 and s215", "and s215 and", "s215 and tp53", "and tp53 degradation", "degradation gully", "gully et al.", "et al. 2012", "al. 2012 .", "of tp53 p53", "p53 at the", "at the n terminal", "the n terminal serine", "n terminal serine residues", "terminal serine residues s15", "serine residues s15 and", "residues s15 and s20", "s15 and s20 plays", "and s20 plays a", "s20 plays a critical", "plays a critical role", "a critical role in", "critical role in protein", "role in protein stabilization", "in protein stabilization as", "protein stabilization as phosphorylation", "stabilization as phosphorylation at", "as phosphorylation at these", "phosphorylation at these sites", "at these sites interferes", "these sites interferes with", "sites interferes with binding", "interferes with binding of", "with binding of the", "binding of the ubiquitin", "of the ubiquitin ligase", "the ubiquitin ligase mdm2", "ubiquitin ligase mdm2 to", "ligase mdm2 to tp53.", "mdm2 to tp53. several", "to tp53. several different", "tp53. several different kinases", "several different kinases can", "different kinases can phosphorylate", "kinases can phosphorylate tp53", "can phosphorylate tp53 at", "phosphorylate tp53 at s15", "tp53 at s15 and", "at s15 and s20.", "s15 and s20. in", "and s20. in response", "s20. in response to", "in response to double", "response to double strand", "to double strand dna", "double strand dna breaks", "dna breaks s15", "breaks s15 is", "s15 is phosphorylated by", "is phosphorylated by atm", "by atm banin", "atm banin et", "banin et al. 1998", "al. 1998 canman", "1998 canman et", "canman et al. 1998", "al. 1998 khanna", "1998 khanna et", "khanna et al. 1998", "1998 and", "and s20 by chek2", "by chek2 chehab", "chek2 chehab et", "chehab et al. 1999", "al. 1999 chehab", "1999 chehab et", "chehab et al. 2000", "al. 2000 hirao", "2000 hirao et", "hirao et al. 2000", "et al. 2000 .", "al. 2000 . dna", "2000 . dna damage", ". dna damage or", "dna damage or other", "damage or other types", "or other types of", "other types of genotoxic", "types of genotoxic stress", "genotoxic stress such", "stress such as", "such as stalled replication", "as stalled replication forks", "replication forks can", "forks can trigger", "can trigger atr mediated", "trigger atr mediated phosphorylation", "atr mediated phosphorylation of", "mediated phosphorylation of tp53", "phosphorylation of tp53 at", "of tp53 at s15", "at s15 lakin", "s15 lakin et", "lakin et al. 1999", "al. 1999 tibbetts", "1999 tibbetts et", "tibbetts et al. 1999", "al. 1999 and", "1999 and chek1", "and chek1 mediated phosphorylation", "chek1 mediated phosphorylation of", "of tp53 at s20", "at s20 shieh", "s20 shieh et", "shieh et al. 2000", "al. 2000 . in", "2000 . in response", ". in response to", "in response to various", "response to various types", "to various types of", "various types of cell", "types of cell stress", "cell stress nuak1", "nuak1 hou et", "hou et al. 2011", "2011 cdk5", "cdk5 zhang et", "zhang et al. 2002", "al. 2002 lee", "2002 lee et", "lee et al. 2007", "al. 2007 lee", "2007 lee et", "lee et al. 2008", "2008 ampk", "ampk jones et", "jones et al. 2005", "al. 2005 and", "2005 and tp53rk", "and tp53rk abe", "tp53rk abe et", "abe et al. 2001", "al. 2001 facchin", "2001 facchin et", "facchin et al. 2003", "al. 2003 can", "2003 can phosphorylate", "at s15 while", "s15 while plk3", "while plk3 xie", "xie wang et", "wang et al. 2001", "al. 2001 xie", "xie wu et", "wu et al. 2001", "al. 2001 can", "2001 can phosphorylate", "phosphorylate tp53 at s20.

phosphorylation", "tp53 at s20.

phosphorylation of", "at s20.

phosphorylation of tp53", "s20.

phosphorylation of tp53 at", "of tp53 at serine", "tp53 at serine residue", "at serine residue s46", "serine residue s46 promotes", "residue s46 promotes transcription", "s46 promotes transcription of", "promotes transcription of tp53", "transcription of tp53 regulated", "of tp53 regulated apoptotic", "tp53 regulated apoptotic genes", "regulated apoptotic genes rather", "apoptotic genes rather than", "genes rather than cell", "rather than cell cycle", "than cell cycle arrest", "cell cycle arrest genes.", "cycle arrest genes. several", "arrest genes. several kinases", "genes. several kinases can", "several kinases can phosphorylate", "kinases can phosphorylate s46", "can phosphorylate s46 of", "phosphorylate s46 of tp53", "of tp53 including", "tp53 including atm", "including atm activated dyrk2", "activated dyrk2 which", "which like tp53", "like tp53 is", "tp53 is targeted", "is targeted for degradation", "targeted for degradation by", "for degradation by mdm2", "by mdm2 taira", "mdm2 taira et", "taira et al. 2007", "al. 2007 taira", "2007 taira et", "taira et al. 2010", "et al. 2010 .", "al. 2010 . tp53", "2010 . tp53 is", ". tp53 is also", "tp53 is also phosphorylated", "is also phosphorylated at", "also phosphorylated at s46", "phosphorylated at s46 by", "at s46 by hipk2", "s46 by hipk2 in", "by hipk2 in the", "hipk2 in the presence", "in the presence of", "the presence of the", "presence of the tp53", "of the tp53 transcriptional", "the tp53 transcriptional target", "tp53 transcriptional target tp53inp1", "target tp53inp1 d'orazi", "tp53inp1 d'orazi et", "d'orazi et al. 2002", "al. 2002 hofmann", "2002 hofmann et", "hofmann et al. 2002", "al. 2002 tomasini", "2002 tomasini et", "tomasini et al. 2003", "et al. 2003 .", "al. 2003 . cdk5", ". cdk5 in", "cdk5 in addition", "in addition to phosphorylating", "addition to phosphorylating tp53", "to phosphorylating tp53 at", "phosphorylating tp53 at s15", "at s15 also", "s15 also phosphorylates", "also phosphorylates it at", "phosphorylates it at s33", "it at s33 and", "at s33 and s46", "and s46 which", "s46 which promotes", "which promotes neuronal cell", "promotes neuronal cell death", "cell death lee", "death lee et", "et al. 2007 .

mapkapk5", "2007 .

mapkapk5 prak", "prak phosphorylates tp53", "phosphorylates tp53 at serine", "at serine residue s37", "residue s37 promoting", "s37 promoting cell", "promoting cell cycle arrest", "cell cycle arrest and", "cycle arrest and cellular", "arrest and cellular senescence", "and cellular senescence in", "cellular senescence in response", "senescence in response to", "in response to oncogenic", "response to oncogenic ras", "to oncogenic ras signaling", "ras signaling sun", "signaling sun et", "sun et al. 2007", "et al. 2007 .

nuak1", "al. 2007 .

nuak1 phosphorylates", "2007 .

nuak1 phosphorylates tp53", ".

nuak1 phosphorylates tp53 at", "phosphorylates tp53 at s15", "at s15 and s392", "and s392 and", "s392 and phosphorylation", "and phosphorylation at s392", "phosphorylation at s392 may", "at s392 may contribute", "s392 may contribute to", "may contribute to tp53", "contribute to tp53 mediated", "to tp53 mediated transcriptional", "tp53 mediated transcriptional activation", "mediated transcriptional activation of", "transcriptional activation of cell", "activation of cell cycle", "of cell cycle arrest", "cell cycle arrest genes", "arrest genes hou", "genes hou et", "et al. 2011 .", "al. 2011 . s392", "2011 . s392 of", ". s392 of tp53", "s392 of tp53 is", "of tp53 is also", "is also phosphorylated by", "also phosphorylated by the", "phosphorylated by the complex", "by the complex of", "the complex of casein", "complex of casein kinase", "of casein kinase ii", "kinase ii ck2", "ck2 bound to", "bound to the fact", "to the fact complex", "fact complex enhancing", "complex enhancing transcriptional", "enhancing transcriptional activity of", "transcriptional activity of tp53", "activity of tp53 in", "of tp53 in response", "tp53 in response to", "in response to uv", "response to uv irradiation", "uv irradiation keller", "irradiation keller et", "keller et al. 2001", "al. 2001 keller", "2001 keller and", "keller and lu 2002", "and lu 2002 .

the", "lu 2002 .

the activity", "2002 .

the activity of", ".

the activity of tp53", "activity of tp53 is", "of tp53 is inhibited", "tp53 is inhibited by", "is inhibited by phosphorylation", "inhibited by phosphorylation at", "by phosphorylation at serine", "phosphorylation at serine residue", "at serine residue s315", "residue s315 which", "s315 which enhances", "which enhances mdm2 binding", "enhances mdm2 binding and", "mdm2 binding and degradation", "binding and degradation of", "and degradation of tp53.", "degradation of tp53. s315", "of tp53. s315 of", "tp53. s315 of tp53", "s315 of tp53 is", "of tp53 is phosphorylated", "tp53 is phosphorylated by", "is phosphorylated by aurora", "phosphorylated by aurora kinase", "by aurora kinase a", "kinase a aurka", "aurka katayama", "katayama et al. 2004", "al. 2004 and", "2004 and cdk2", "and cdk2 luciani", "cdk2 luciani et", "luciani et al. 2000", "al. 2000 . interaction", "2000 . interaction with", ". interaction with mdm2", "interaction with mdm2 and", "with mdm2 and the", "mdm2 and the consequent", "and the consequent tp53", "the consequent tp53 degradation", "consequent tp53 degradation is", "tp53 degradation is also", "degradation is also increased", "is also increased by", "also increased by phosphorylation", "increased by phosphorylation of", "by phosphorylation of tp53", "phosphorylation of tp53 threonine", "of tp53 threonine residue", "tp53 threonine residue t55", "threonine residue t55 by", "residue t55 by the", "t55 by the transcription", "by the transcription initiation", "the transcription initiation factor", "transcription initiation factor complex", "initiation factor complex tfiid", "complex tfiid li", "tfiid li et", "li et al. 2004", "et al. 2004 .

aurora", "al. 2004 .

aurora kinase", "2004 .

aurora kinase b", "kinase b aurkb", "aurkb has been", "has been shown to", "been shown to phosphorylate", "shown to phosphorylate tp53", "to phosphorylate tp53 at", "phosphorylate tp53 at serine", "at serine residue s269", "serine residue s269 and", "residue s269 and threonine", "s269 and threonine residue", "and threonine residue t284", "residue t284 which", "t284 which is", "which is possibly facilitated", "is possibly facilitated by", "possibly facilitated by the", "facilitated by the binding", "by the binding of", "the binding of the", "binding of the nir", "of the nir co", "the nir co repressor.", "nir co repressor. aurkb", "co repressor. aurkb mediated", "repressor. aurkb mediated phosphorylation", "aurkb mediated phosphorylation was", "mediated phosphorylation was reported", "phosphorylation was reported to", "was reported to inhibit", "reported to inhibit tp53", "to inhibit tp53 transcriptional", "inhibit tp53 transcriptional activity", "tp53 transcriptional activity through", "transcriptional activity through an", "activity through an unknown", "through an unknown mechanism", "unknown mechanism wu", "mechanism wu et", "wu et al. 2011", "al. 2011 . a", "2011 . a putative", ". a putative direct", "a putative direct interaction", "putative direct interaction between", "direct interaction between tp53", "interaction between tp53 and", "between tp53 and aurkb", "tp53 and aurkb has", "and aurkb has also", "aurkb has also been", "has also been described", "also been described and", "been described and linked", "described and linked to", "and linked to tp53", "linked to tp53 phosphorylation", "to tp53 phosphorylation and", "tp53 phosphorylation and s183", "and s183 t211", "s183 t211 and", "t211 and s215 and", "and s215 and tp53", "s215 and tp53 degradation", "tp53 degradation gully", "degradation gully et", "gully et al. 2012", "et al. 2012 .", "phosphorylation of tp53 p53", "tp53 p53 at", "p53 at the n", "at the n terminal serine", "the n terminal serine residues", "n terminal serine residues s15", "terminal serine residues s15 and", "serine residues s15 and s20", "residues s15 and s20 plays", "s15 and s20 plays a", "and s20 plays a critical", "s20 plays a critical role", "plays a critical role in", "a critical role in protein", "critical role in protein stabilization", "role in protein stabilization as", "in protein stabilization as phosphorylation", "protein stabilization as phosphorylation at", "stabilization as phosphorylation at these", "as phosphorylation at these sites", "phosphorylation at these sites interferes", "at these sites interferes with", "these sites interferes with binding", "sites interferes with binding of", "interferes with binding of the", "with binding of the ubiquitin", "binding of the ubiquitin ligase", "of the ubiquitin ligase mdm2", "the ubiquitin ligase mdm2 to", "ubiquitin ligase mdm2 to tp53.", "ligase mdm2 to tp53. several", "mdm2 to tp53. several different", "to tp53. several different kinases", "tp53. several different kinases can", "several different kinases can phosphorylate", "different kinases can phosphorylate tp53", "kinases can phosphorylate tp53 at", "can phosphorylate tp53 at s15", "phosphorylate tp53 at s15 and", "tp53 at s15 and s20.", "at s15 and s20. in", "s15 and s20. in response", "and s20. in response to", "s20. in response to double", "in response to double strand", "response to double strand dna", "to double strand dna breaks", "strand dna breaks s15", "dna breaks s15 is", "breaks s15 is phosphorylated", "s15 is phosphorylated by atm", "phosphorylated by atm banin", "by atm banin et", "atm banin et al.", "et al. 1998 canman", "al. 1998 canman et", "1998 canman et al.", "et al. 1998 khanna", "al. 1998 khanna et", "1998 khanna et al.", "al. 1998 and", "1998 and s20", "s20 by chek2 chehab", "by chek2 chehab et", "chek2 chehab et al.", "et al. 1999 chehab", "al. 1999 chehab et", "1999 chehab et al.", "et al. 2000 hirao", "al. 2000 hirao et", "2000 hirao et al.", "hirao et al. 2000 .", "et al. 2000 . dna", "al. 2000 . dna damage", "2000 . dna damage or", ". dna damage or other", "dna damage or other types", "damage or other types of", "or other types of genotoxic", "other types of genotoxic stress", "of genotoxic stress such", "genotoxic stress such as", "stress such as stalled", "such as stalled replication forks", "stalled replication forks can", "replication forks can trigger", "forks can trigger atr", "can trigger atr mediated phosphorylation", "trigger atr mediated phosphorylation of", "atr mediated phosphorylation of tp53", "mediated phosphorylation of tp53 at", "phosphorylation of tp53 at s15", "tp53 at s15 lakin", "at s15 lakin et", "s15 lakin et al.", "et al. 1999 tibbetts", "al. 1999 tibbetts et", "1999 tibbetts et al.", "et al. 1999 and", "al. 1999 and chek1", "1999 and chek1 mediated", "and chek1 mediated phosphorylation of", "chek1 mediated phosphorylation of tp53", "phosphorylation of tp53 at s20", "tp53 at s20 shieh", "at s20 shieh et", "s20 shieh et al.", "shieh et al. 2000 .", "et al. 2000 . in", "al. 2000 . in response", "2000 . in response to", ". in response to various", "in response to various types", "response to various types of", "to various types of cell", "various types of cell stress", "of cell stress nuak1", "stress nuak1 hou", "nuak1 hou et al.", "al. 2011 cdk5", "cdk5 zhang et al.", "et al. 2002 lee", "al. 2002 lee et", "2002 lee et al.", "et al. 2007 lee", "al. 2007 lee et", "2007 lee et al.", "al. 2008 ampk", "ampk jones et al.", "et al. 2005 and", "al. 2005 and tp53rk", "and tp53rk abe et", "tp53rk abe et al.", "et al. 2001 facchin", "al. 2001 facchin et", "2001 facchin et al.", "et al. 2003 can", "al. 2003 can phosphorylate", "2003 can phosphorylate tp53", "tp53 at s15 while", "at s15 while plk3", "plk3 xie wang", "xie wang et al.", "et al. 2001 xie", "2001 xie wu", "xie wu et al.", "et al. 2001 can", "al. 2001 can phosphorylate", "2001 can phosphorylate tp53", "can phosphorylate tp53 at s20.

phosphorylation", "phosphorylate tp53 at s20.

phosphorylation of", "tp53 at s20.

phosphorylation of tp53", "at s20.

phosphorylation of tp53 at", "s20.

phosphorylation of tp53 at serine", "of tp53 at serine residue", "tp53 at serine residue s46", "at serine residue s46 promotes", "serine residue s46 promotes transcription", "residue s46 promotes transcription of", "s46 promotes transcription of tp53", "promotes transcription of tp53 regulated", "transcription of tp53 regulated apoptotic", "of tp53 regulated apoptotic genes", "tp53 regulated apoptotic genes rather", "regulated apoptotic genes rather than", "apoptotic genes rather than cell", "genes rather than cell cycle", "rather than cell cycle arrest", "than cell cycle arrest genes.", "cell cycle arrest genes. several", "cycle arrest genes. several kinases", "arrest genes. several kinases can", "genes. several kinases can phosphorylate", "several kinases can phosphorylate s46", "kinases can phosphorylate s46 of", "can phosphorylate s46 of tp53", "s46 of tp53 including", "of tp53 including atm", "tp53 including atm activated", "atm activated dyrk2 which", "dyrk2 which like", "like tp53 is targeted", "tp53 is targeted for", "is targeted for degradation by", "targeted for degradation by mdm2", "degradation by mdm2 taira", "by mdm2 taira et", "mdm2 taira et al.", "et al. 2007 taira", "al. 2007 taira et", "2007 taira et al.", "taira et al. 2010 .", "et al. 2010 . tp53", "al. 2010 . tp53 is", "2010 . tp53 is also", ". tp53 is also phosphorylated", "tp53 is also phosphorylated at", "is also phosphorylated at s46", "also phosphorylated at s46 by", "phosphorylated at s46 by hipk2", "at s46 by hipk2 in", "s46 by hipk2 in the", "by hipk2 in the presence", "hipk2 in the presence of", "in the presence of the", "the presence of the tp53", "presence of the tp53 transcriptional", "of the tp53 transcriptional target", "the tp53 transcriptional target tp53inp1", "transcriptional target tp53inp1 d'orazi", "target tp53inp1 d'orazi et", "tp53inp1 d'orazi et al.", "et al. 2002 hofmann", "al. 2002 hofmann et", "2002 hofmann et al.", "et al. 2002 tomasini", "al. 2002 tomasini et", "2002 tomasini et al.", "tomasini et al. 2003 .", "et al. 2003 . cdk5", "2003 . cdk5 in", ". cdk5 in addition", "cdk5 in addition to", "in addition to phosphorylating tp53", "addition to phosphorylating tp53 at", "to phosphorylating tp53 at s15", "tp53 at s15 also", "at s15 also phosphorylates", "s15 also phosphorylates it", "also phosphorylates it at s33", "phosphorylates it at s33 and", "it at s33 and s46", "s33 and s46 which", "and s46 which promotes", "s46 which promotes neuronal", "which promotes neuronal cell death", "neuronal cell death lee", "cell death lee et", "death lee et al.", "lee et al. 2007 .

mapkapk5", "al. 2007 .

mapkapk5 prak", ".

mapkapk5 prak phosphorylates", "prak phosphorylates tp53 at", "phosphorylates tp53 at serine residue", "tp53 at serine residue s37", "serine residue s37 promoting", "residue s37 promoting cell", "s37 promoting cell cycle", "promoting cell cycle arrest and", "cell cycle arrest and cellular", "cycle arrest and cellular senescence", "arrest and cellular senescence in", "and cellular senescence in response", "cellular senescence in response to", "senescence in response to oncogenic", "in response to oncogenic ras", "response to oncogenic ras signaling", "oncogenic ras signaling sun", "ras signaling sun et", "signaling sun et al.", "sun et al. 2007 .

nuak1", "et al. 2007 .

nuak1 phosphorylates", "al. 2007 .

nuak1 phosphorylates tp53", "2007 .

nuak1 phosphorylates tp53 at", ".

nuak1 phosphorylates tp53 at s15", "phosphorylates tp53 at s15 and", "tp53 at s15 and s392", "s15 and s392 and", "and s392 and phosphorylation", "s392 and phosphorylation at", "and phosphorylation at s392 may", "phosphorylation at s392 may contribute", "at s392 may contribute to", "s392 may contribute to tp53", "may contribute to tp53 mediated", "contribute to tp53 mediated transcriptional", "to tp53 mediated transcriptional activation", "tp53 mediated transcriptional activation of", "mediated transcriptional activation of cell", "transcriptional activation of cell cycle", "activation of cell cycle arrest", "of cell cycle arrest genes", "cycle arrest genes hou", "arrest genes hou et", "genes hou et al.", "hou et al. 2011 .", "et al. 2011 . s392", "al. 2011 . s392 of", "2011 . s392 of tp53", ". s392 of tp53 is", "s392 of tp53 is also", "of tp53 is also phosphorylated", "tp53 is also phosphorylated by", "is also phosphorylated by the", "also phosphorylated by the complex", "phosphorylated by the complex of", "by the complex of casein", "the complex of casein kinase", "complex of casein kinase ii", "casein kinase ii ck2", "ii ck2 bound", "ck2 bound to the", "bound to the fact complex", "the fact complex enhancing", "fact complex enhancing transcriptional", "complex enhancing transcriptional activity", "enhancing transcriptional activity of tp53", "transcriptional activity of tp53 in", "activity of tp53 in response", "of tp53 in response to", "tp53 in response to uv", "in response to uv irradiation", "to uv irradiation keller", "uv irradiation keller et", "irradiation keller et al.", "et al. 2001 keller", "al. 2001 keller and", "2001 keller and lu", "keller and lu 2002 .

the", "and lu 2002 .

the activity", "lu 2002 .

the activity of", "2002 .

the activity of tp53", ".

the activity of tp53 is", "activity of tp53 is inhibited", "of tp53 is inhibited by", "tp53 is inhibited by phosphorylation", "is inhibited by phosphorylation at", "inhibited by phosphorylation at serine", "by phosphorylation at serine residue", "phosphorylation at serine residue s315", "serine residue s315 which", "residue s315 which enhances", "s315 which enhances mdm2", "which enhances mdm2 binding and", "enhances mdm2 binding and degradation", "mdm2 binding and degradation of", "binding and degradation of tp53.", "and degradation of tp53. s315", "degradation of tp53. s315 of", "of tp53. s315 of tp53", "tp53. s315 of tp53 is", "s315 of tp53 is phosphorylated", "of tp53 is phosphorylated by", "tp53 is phosphorylated by aurora", "is phosphorylated by aurora kinase", "phosphorylated by aurora kinase a", "aurora kinase a aurka", "aurka katayama et", "et al. 2004 and", "al. 2004 and cdk2", "and cdk2 luciani et", "cdk2 luciani et al.", "luciani et al. 2000 .", "et al. 2000 . interaction", "al. 2000 . interaction with", "2000 . interaction with mdm2", ". interaction with mdm2 and", "interaction with mdm2 and the", "with mdm2 and the consequent", "mdm2 and the consequent tp53", "and the consequent tp53 degradation", "the consequent tp53 degradation is", "consequent tp53 degradation is also", "tp53 degradation is also increased", "degradation is also increased by", "is also increased by phosphorylation", "also increased by phosphorylation of", "increased by phosphorylation of tp53", "by phosphorylation of tp53 threonine", "phosphorylation of tp53 threonine residue", "of tp53 threonine residue t55", "tp53 threonine residue t55 by", "threonine residue t55 by the", "residue t55 by the transcription", "t55 by the transcription initiation", "by the transcription initiation factor", "the transcription initiation factor complex", "transcription initiation factor complex tfiid", "factor complex tfiid li", "complex tfiid li et", "tfiid li et al.", "li et al. 2004 .

aurora", "et al. 2004 .

aurora kinase", "al. 2004 .

aurora kinase b", ".

aurora kinase b aurkb", "b aurkb has", "aurkb has been shown", "has been shown to phosphorylate", "been shown to phosphorylate tp53", "shown to phosphorylate tp53 at", "to phosphorylate tp53 at serine", "phosphorylate tp53 at serine residue", "tp53 at serine residue s269", "at serine residue s269 and", "serine residue s269 and threonine", "residue s269 and threonine residue", "s269 and threonine residue t284", "threonine residue t284 which", "residue t284 which is", "t284 which is possibly", "which is possibly facilitated by", "is possibly facilitated by the", "possibly facilitated by the binding", "facilitated by the binding of", "by the binding of the", "the binding of the nir", "binding of the nir co", "of the nir co repressor.", "the nir co repressor. aurkb", "nir co repressor. aurkb mediated", "co repressor. aurkb mediated phosphorylation", "repressor. aurkb mediated phosphorylation was", "aurkb mediated phosphorylation was reported", "mediated phosphorylation was reported to", "phosphorylation was reported to inhibit", "was reported to inhibit tp53", "reported to inhibit tp53 transcriptional", "to inhibit tp53 transcriptional activity", "inhibit tp53 transcriptional activity through", "tp53 transcriptional activity through an", "transcriptional activity through an unknown", "activity through an unknown mechanism", "an unknown mechanism wu", "unknown mechanism wu et", "mechanism wu et al.", "wu et al. 2011 .", "et al. 2011 . a", "al. 2011 . a putative", "2011 . a putative direct", ". a putative direct interaction", "a putative direct interaction between", "putative direct interaction between tp53", "direct interaction between tp53 and", "interaction between tp53 and aurkb", "between tp53 and aurkb has", "tp53 and aurkb has also", "and aurkb has also been", "aurkb has also been described", "has also been described and", "also been described and linked", "been described and linked to", "described and linked to tp53", "and linked to tp53 phosphorylation", "linked to tp53 phosphorylation and", "to tp53 phosphorylation and s183", "phosphorylation and s183 t211", "and s183 t211 and", "s183 t211 and s215", "t211 and s215 and tp53", "and s215 and tp53 degradation", "and tp53 degradation gully", "tp53 degradation gully et", "degradation gully et al.", "gully et al. 2012 ." ] }, { "record_id": "GLY_000594_1_531", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6804757", "r hsa", "hsa 6804757", "r hsa 6804757" ] }, { "record_id": "GLY_000594_1_531", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of tp53", "tp53 degradation", "regulation of tp53", "of tp53 degradation", "regulation of tp53 degradation", "in unstressed", "unstressed cells", "has a", "a short", "short half", "half life", "life as", "as it", "it undergoes", "undergoes rapid", "rapid ubiquitination", "ubiquitination and", "and proteasome", "proteasome mediated", "mediated degradation.", "degradation. the", "the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase mdm2", "which is", "is a", "a transcriptional", "transcriptional target", "target of", "plays the", "the main", "main role", "role in", "in tp53", "tp53 protein", "protein down", "down regulation", "wu et", "et al.", "al. 1993", "1993 .", ". mdm2", "mdm2 forms", "forms homodimers", "homodimers and", "and homo", "homo oligomers", "but also", "also functions", "functions as", "as a", "a heterodimer/hetero", "heterodimer/hetero oligomer", "oligomer with", "with mdm4", "sharp et", "al. 1999", "cheng et", "al. 2011", "huang et", "pant et", "2011 .", ". the", "the heterodimers", "heterodimers of", "of mdm2", "mdm2 and", "and mdm4", "mdm4 may", "may be", "be especially", "especially important", "important for", "for downregulation", "downregulation of", "tp53 during", "during embryonic", "embryonic development", "2011 .

the", ".

the nuclear", "nuclear localization", "localization of", "mdm2 is", "is positively", "positively regulated", "regulated by", "by akt", "or sgk1", "mediated phosphorylation", "mayo and", "and donner", "donner 2001", "zhou et", "al. 2001", "amato et", "al. 2009", "lyo et", "al. 2010", "2010 .", ". phosphorylation", "phosphorylation of", "mdm2 by", "by cdk1", "cdk1 or", "or cdk2", "cdk2 decreases", "decreases affinity", "affinity of", "mdm2 for", "for tp53", "zhang and", "and prives", "prives 2001", "2001 .", ". atm", "atm and", "and chek2", "chek2 kinases", "activated by", "by double", "double strand", "strand dna", "dna breaks", "phosphorylate tp53", "reducing its", "its affinity", "affinity for", "for mdm2", "banin et", "al. 1998", "canman et", "khanna et", "chehab et", "al. 2000", "2000 .", ". at", "at the", "the same", "same time", "atm phosphorylates", "phosphorylates mdm2", "preventing mdm2", "mdm2 dimerization", ". both", "both atm", "chek2 phosphorylate", "phosphorylate mdm4", "triggering mdm2", "mdm2 mediated", "mediated ubiquitination", "ubiquitination of", "of mdm4", "chen et", "al. 2005", "pereg et", "2005 .", ". cyclin", "cyclin g1", "transcriptionally induced", "induced by", "by tp53", "targets the", "the pp2a", "pp2a phosphatase", "phosphatase complex", "complex to", "to mdm2", "resulting in", "in dephosphorylation", "dephosphorylation of", "mdm2 at", "at specific", "specific sites", "which can", "can have", "have either", "either a", "a positive", "positive or", "or a", "a negative", "negative impact", "impact on", "on mdm2", "mdm2 function", "okamoto et", "al. 2002", "2002 .

in", ".

in contrast", "contrast to", "ubiquitin ligases", "ligases rnf34", "and rffl", "can ubiquitinate", "ubiquitinate phosphorylated", "phosphorylated tp53", "yang et", "al. 2007", "2007 .

in", ".

in addition", "addition to", "to ubiquitinating", "ubiquitinating mdm4", "mdm2 can", "can also", "also undergo", "undergo auto", "auto ubiquitination", "fang et", "mdm4 can", "can be", "be deubiquitinated", "deubiquitinated by", "by the", "the ubiquitin", "ubiquitin protease", "protease usp2", "stevenson et", "allende vega", "vega et", "protease usp7", "usp7 can", "can deubiquitinate", "deubiquitinate tp53", "but in", "in the", "the presence", "presence of", "of daxx", "daxx deubiquitinates", "deubiquitinates mdm2", "li et", "sheng et", "al. 2006", "tang et", "2006 .

the", ".

the tumor", "tumor suppressor", "suppressor p14", "p14 arf", "expressed from", "from the", "the cdkn2a", "cdkn2a gene", "gene in", "in response", "response to", "to oncogenic", "oncogenic or", "or oxidative", "oxidative stress", "forms a", "a tripartite", "tripartite complex", "complex with", "with mdm2", "and tp53", "sequesters mdm2", "mdm2 from", "from tp53", "and thus", "thus prevents", "prevents tp53", "zhang et", "parisi et", "voncken et", "2005 .

for", ".

for review", "review of", "of this", "this topic", "please refer", "refer to", "to kruse", "kruse and", "and gu", "gu 2009.", "in unstressed cells", "cells tp53", "tp53 p53", "p53 has", "has a short", "a short half", "short half life", "half life as", "life as it", "as it undergoes", "it undergoes rapid", "undergoes rapid ubiquitination", "rapid ubiquitination and", "ubiquitination and proteasome", "and proteasome mediated", "proteasome mediated degradation.", "mediated degradation. the", "degradation. the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase mdm2", "mdm2 which", "which is a", "is a transcriptional", "a transcriptional target", "transcriptional target of", "target of tp53", "tp53 plays", "plays the main", "the main role", "main role in", "role in tp53", "in tp53 protein", "tp53 protein down", "protein down regulation", "regulation wu", "wu et al.", "et al. 1993", "al. 1993 .", "1993 . mdm2", ". mdm2 forms", "mdm2 forms homodimers", "forms homodimers and", "homodimers and homo", "and homo oligomers", "oligomers but", "but also functions", "also functions as", "functions as a", "as a heterodimer/hetero", "a heterodimer/hetero oligomer", "heterodimer/hetero oligomer with", "oligomer with mdm4", "mdm4 mdmx", "sharp et al.", "et al. 1999", "1999 cheng", "cheng et al.", "et al. 2011", "2011 huang", "huang et al.", "2011 pant", "pant et al.", "al. 2011 .", "2011 . the", ". the heterodimers", "the heterodimers of", "heterodimers of mdm2", "of mdm2 and", "mdm2 and mdm4", "and mdm4 may", "mdm4 may be", "may be especially", "be especially important", "especially important for", "important for downregulation", "for downregulation of", "downregulation of tp53", "of tp53 during", "tp53 during embryonic", "during embryonic development", "development pant", "al. 2011 .

the", "2011 .

the nuclear", ".

the nuclear localization", "nuclear localization of", "localization of mdm2", "of mdm2 is", "mdm2 is positively", "is positively regulated", "positively regulated by", "regulated by akt", "akt or", "sgk1 mediated", "phosphorylation mayo", "mayo and donner", "and donner 2001", "2001 zhou", "zhou et al.", "et al. 2001", "2001 amato", "amato et al.", "et al. 2009", "2009 lyo", "lyo et al.", "et al. 2010", "al. 2010 .", "2010 . phosphorylation", ". phosphorylation of", "phosphorylation of mdm2", "of mdm2 by", "mdm2 by cdk1", "by cdk1 or", "cdk1 or cdk2", "or cdk2 decreases", "cdk2 decreases affinity", "decreases affinity of", "affinity of mdm2", "of mdm2 for", "mdm2 for tp53", "tp53 zhang", "zhang and prives", "and prives 2001", "prives 2001 .", "2001 . atm", ". atm and", "atm and chek2", "and chek2 kinases", "kinases activated", "activated by double", "by double strand", "double strand dna", "strand dna breaks", "breaks phosphorylate", "tp53 reducing", "reducing its affinity", "its affinity for", "affinity for mdm2", "mdm2 banin", "banin et al.", "et al. 1998", "1998 canman", "canman et al.", "1998 khanna", "khanna et al.", "1998 chehab", "chehab et al.", "1999 chehab", "et al. 2000", "al. 2000 .", "2000 . at", ". at the", "at the same", "the same time", "time atm", "atm phosphorylates mdm2", "mdm2 preventing", "preventing mdm2 dimerization", "dimerization cheng", "2009 cheng", "2011 . both", ". both atm", "both atm and", "and chek2 phosphorylate", "chek2 phosphorylate mdm4", "mdm4 triggering", "triggering mdm2 mediated", "mdm2 mediated ubiquitination", "mediated ubiquitination of", "ubiquitination of mdm4", "mdm4 chen", "chen et al.", "et al. 2005", "2005 pereg", "pereg et al.", "al. 2005 .", "2005 . cyclin", ". cyclin g1", "g1 ccng1", "transcriptionally induced by", "induced by tp53", "tp53 targets", "targets the pp2a", "the pp2a phosphatase", "pp2a phosphatase complex", "phosphatase complex to", "complex to mdm2", "mdm2 resulting", "resulting in dephosphorylation", "in dephosphorylation of", "dephosphorylation of mdm2", "of mdm2 at", "mdm2 at specific", "at specific sites", "sites which", "which can have", "can have either", "have either a", "either a positive", "a positive or", "positive or a", "or a negative", "a negative impact", "negative impact on", "impact on mdm2", "on mdm2 function", "function okamoto", "okamoto et al.", "et al. 2002", "al. 2002 .

in", "2002 .

in contrast", ".

in contrast to", "contrast to mdm2", "mdm2 e3", "e3 ubiquitin ligases", "ubiquitin ligases rnf34", "rnf34 carp1", "carp1 and", "rffl carp2", "carp2 can", "can ubiquitinate phosphorylated", "ubiquitinate phosphorylated tp53", "tp53 yang", "yang et al.", "et al. 2007", "al. 2007 .

in", "2007 .

in addition", ".

in addition to", "addition to ubiquitinating", "to ubiquitinating mdm4", "mdm4 pereg", "mdm2 can also", "can also undergo", "also undergo auto", "undergo auto ubiquitination", "ubiquitination fang", "fang et al.", "2000 . mdm2", ". mdm2 and", "and mdm4 can", "mdm4 can be", "can be deubiquitinated", "be deubiquitinated by", "deubiquitinated by the", "by the ubiquitin", "the ubiquitin protease", "ubiquitin protease usp2", "usp2 stevenson", "stevenson et al.", "2007 allende", "allende vega et", "vega et al.", "2010 . the", ". the ubiquitin", "ubiquitin protease usp7", "protease usp7 can", "usp7 can deubiquitinate", "can deubiquitinate tp53", "tp53 but", "but in the", "in the presence", "the presence of", "presence of daxx", "of daxx deubiquitinates", "daxx deubiquitinates mdm2", "mdm2 li", "li et al.", "2002 sheng", "sheng et al.", "et al. 2006", "2006 tang", "tang et al.", "al. 2006 .

the", "2006 .

the tumor", ".

the tumor suppressor", "tumor suppressor p14", "suppressor p14 arf", "arf expressed", "expressed from the", "from the cdkn2a", "the cdkn2a gene", "cdkn2a gene in", "gene in response", "in response to", "response to oncogenic", "to oncogenic or", "oncogenic or oxidative", "or oxidative stress", "stress forms", "forms a tripartite", "a tripartite complex", "tripartite complex with", "complex with mdm2", "with mdm2 and", "mdm2 and tp53", "tp53 sequesters", "sequesters mdm2 from", "mdm2 from tp53", "tp53 and", "and thus prevents", "thus prevents tp53", "prevents tp53 degradation", "degradation zhang", "zhang et al.", "1998 parisi", "parisi et al.", "2002 voncken", "voncken et al.", "al. 2005 .

for", "2005 .

for review", ".

for review of", "review of this", "of this topic", "topic please", "please refer to", "refer to kruse", "to kruse and", "kruse and gu", "and gu 2009.", "unstressed cells tp53", "p53 has a", "has a short half", "a short half life", "short half life as", "half life as it", "life as it undergoes", "as it undergoes rapid", "it undergoes rapid ubiquitination", "undergoes rapid ubiquitination and", "rapid ubiquitination and proteasome", "ubiquitination and proteasome mediated", "and proteasome mediated degradation.", "proteasome mediated degradation. the", "mediated degradation. the e3", "degradation. the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase mdm2", "ligase mdm2 which", "mdm2 which is", "which is a transcriptional", "is a transcriptional target", "a transcriptional target of", "transcriptional target of tp53", "of tp53 plays", "tp53 plays the", "plays the main role", "the main role in", "main role in tp53", "role in tp53 protein", "in tp53 protein down", "tp53 protein down regulation", "down regulation wu", "regulation wu et", "wu et al. 1993", "et al. 1993 .", "al. 1993 . mdm2", "1993 . mdm2 forms", ". mdm2 forms homodimers", "mdm2 forms homodimers and", "forms homodimers and homo", "homodimers and homo oligomers", "homo oligomers but", "oligomers but also", "but also functions as", "also functions as a", "functions as a heterodimer/hetero", "as a heterodimer/hetero oligomer", "a heterodimer/hetero oligomer with", "heterodimer/hetero oligomer with mdm4", "with mdm4 mdmx", "mdmx sharp", "sharp et al. 1999", "al. 1999 cheng", "1999 cheng et", "cheng et al. 2011", "al. 2011 huang", "2011 huang et", "huang et al. 2011", "al. 2011 pant", "2011 pant et", "pant et al. 2011", "et al. 2011 .", "al. 2011 . the", "2011 . the heterodimers", ". the heterodimers of", "the heterodimers of mdm2", "heterodimers of mdm2 and", "of mdm2 and mdm4", "mdm2 and mdm4 may", "and mdm4 may be", "mdm4 may be especially", "may be especially important", "be especially important for", "especially important for downregulation", "important for downregulation of", "for downregulation of tp53", "downregulation of tp53 during", "of tp53 during embryonic", "tp53 during embryonic development", "embryonic development pant", "development pant et", "et al. 2011 .

the", "al. 2011 .

the nuclear", "2011 .

the nuclear localization", ".

the nuclear localization of", "nuclear localization of mdm2", "localization of mdm2 is", "of mdm2 is positively", "mdm2 is positively regulated", "is positively regulated by", "positively regulated by akt", "by akt or", "akt or sgk1", "or sgk1 mediated", "sgk1 mediated phosphorylation", "mediated phosphorylation mayo", "phosphorylation mayo and", "mayo and donner 2001", "donner 2001 zhou", "2001 zhou et", "zhou et al. 2001", "al. 2001 amato", "2001 amato et", "amato et al. 2009", "al. 2009 lyo", "2009 lyo et", "lyo et al. 2010", "et al. 2010 .", "al. 2010 . phosphorylation", "2010 . phosphorylation of", ". phosphorylation of mdm2", "phosphorylation of mdm2 by", "of mdm2 by cdk1", "mdm2 by cdk1 or", "by cdk1 or cdk2", "cdk1 or cdk2 decreases", "or cdk2 decreases affinity", "cdk2 decreases affinity of", "decreases affinity of mdm2", "affinity of mdm2 for", "of mdm2 for tp53", "for tp53 zhang", "tp53 zhang and", "zhang and prives 2001", "and prives 2001 .", "prives 2001 . atm", "2001 . atm and", ". atm and chek2", "atm and chek2 kinases", "chek2 kinases activated", "kinases activated by", "activated by double strand", "by double strand dna", "double strand dna breaks", "dna breaks phosphorylate", "breaks phosphorylate tp53", "phosphorylate tp53 reducing", "tp53 reducing its", "reducing its affinity for", "its affinity for mdm2", "for mdm2 banin", "mdm2 banin et", "banin et al. 1998", "al. 1998 canman", "1998 canman et", "canman et al. 1998", "al. 1998 khanna", "1998 khanna et", "khanna et al. 1998", "al. 1998 chehab", "1998 chehab et", "chehab et al. 1999", "al. 1999 chehab", "1999 chehab et", "chehab et al. 2000", "et al. 2000 .", "al. 2000 . at", "2000 . at the", ". at the same", "at the same time", "same time atm", "time atm phosphorylates", "phosphorylates mdm2 preventing", "mdm2 preventing mdm2", "mdm2 dimerization cheng", "dimerization cheng et", "cheng et al. 2009", "al. 2009 cheng", "2009 cheng et", "al. 2011 . both", "2011 . both atm", ". both atm and", "both atm and chek2", "atm and chek2 phosphorylate", "and chek2 phosphorylate mdm4", "phosphorylate mdm4 triggering", "mdm4 triggering mdm2", "triggering mdm2 mediated ubiquitination", "mdm2 mediated ubiquitination of", "mediated ubiquitination of mdm4", "of mdm4 chen", "mdm4 chen et", "chen et al. 2005", "al. 2005 pereg", "2005 pereg et", "pereg et al. 2005", "et al. 2005 .", "al. 2005 . cyclin", "2005 . cyclin g1", "cyclin g1 ccng1", "ccng1 transcriptionally", "transcriptionally induced by tp53", "by tp53 targets", "tp53 targets the", "targets the pp2a phosphatase", "the pp2a phosphatase complex", "pp2a phosphatase complex to", "phosphatase complex to mdm2", "to mdm2 resulting", "mdm2 resulting in", "resulting in dephosphorylation of", "in dephosphorylation of mdm2", "dephosphorylation of mdm2 at", "of mdm2 at specific", "mdm2 at specific sites", "specific sites which", "sites which can", "which can have either", "can have either a", "have either a positive", "either a positive or", "a positive or a", "positive or a negative", "or a negative impact", "a negative impact on", "negative impact on mdm2", "impact on mdm2 function", "mdm2 function okamoto", "function okamoto et", "okamoto et al. 2002", "et al. 2002 .

in", "al. 2002 .

in contrast", "2002 .

in contrast to", ".

in contrast to mdm2", "to mdm2 e3", "mdm2 e3 ubiquitin", "e3 ubiquitin ligases rnf34", "ligases rnf34 carp1", "carp1 and rffl", "and rffl carp2", "carp2 can ubiquitinate", "can ubiquitinate phosphorylated tp53", "phosphorylated tp53 yang", "tp53 yang et", "yang et al. 2007", "et al. 2007 .

in", "al. 2007 .

in addition", "2007 .

in addition to", ".

in addition to ubiquitinating", "addition to ubiquitinating mdm4", "ubiquitinating mdm4 pereg", "mdm4 pereg et", "2005 mdm2", "mdm2 can also undergo", "can also undergo auto", "also undergo auto ubiquitination", "auto ubiquitination fang", "ubiquitination fang et", "fang et al. 2000", "al. 2000 . mdm2", "2000 . mdm2 and", ". mdm2 and mdm4", "mdm2 and mdm4 can", "and mdm4 can be", "mdm4 can be deubiquitinated", "can be deubiquitinated by", "be deubiquitinated by the", "deubiquitinated by the ubiquitin", "by the ubiquitin protease", "the ubiquitin protease usp2", "protease usp2 stevenson", "usp2 stevenson et", "stevenson et al. 2007", "al. 2007 allende", "2007 allende vega", "allende vega et al.", "vega et al. 2010", "al. 2010 . the", "2010 . the ubiquitin", ". the ubiquitin protease", "the ubiquitin protease usp7", "ubiquitin protease usp7 can", "protease usp7 can deubiquitinate", "usp7 can deubiquitinate tp53", "deubiquitinate tp53 but", "tp53 but in", "but in the presence", "in the presence of", "the presence of daxx", "presence of daxx deubiquitinates", "of daxx deubiquitinates mdm2", "deubiquitinates mdm2 li", "mdm2 li et", "li et al. 2002", "al. 2002 sheng", "2002 sheng et", "sheng et al. 2006", "al. 2006 tang", "2006 tang et", "tang et al. 2006", "et al. 2006 .

the", "al. 2006 .

the tumor", "2006 .

the tumor suppressor", ".

the tumor suppressor p14", "tumor suppressor p14 arf", "p14 arf expressed", "arf expressed from", "expressed from the cdkn2a", "from the cdkn2a gene", "the cdkn2a gene in", "cdkn2a gene in response", "gene in response to", "in response to oncogenic", "response to oncogenic or", "to oncogenic or oxidative", "oncogenic or oxidative stress", "oxidative stress forms", "stress forms a", "forms a tripartite complex", "a tripartite complex with", "tripartite complex with mdm2", "complex with mdm2 and", "with mdm2 and tp53", "and tp53 sequesters", "tp53 sequesters mdm2", "sequesters mdm2 from tp53", "from tp53 and", "tp53 and thus", "and thus prevents tp53", "thus prevents tp53 degradation", "tp53 degradation zhang", "degradation zhang et", "zhang et al. 1998", "al. 1998 parisi", "1998 parisi et", "parisi et al. 2002", "al. 2002 voncken", "2002 voncken et", "voncken et al. 2005", "et al. 2005 .

for", "al. 2005 .

for review", "2005 .

for review of", ".

for review of this", "review of this topic", "this topic please", "topic please refer", "please refer to kruse", "refer to kruse and", "to kruse and gu", "kruse and gu 2009.", "in unstressed cells tp53", "cells tp53 p53", "tp53 p53 has", "p53 has a short", "has a short half life", "a short half life as", "short half life as it", "half life as it undergoes", "life as it undergoes rapid", "as it undergoes rapid ubiquitination", "it undergoes rapid ubiquitination and", "undergoes rapid ubiquitination and proteasome", "rapid ubiquitination and proteasome mediated", "ubiquitination and proteasome mediated degradation.", "and proteasome mediated degradation. the", "proteasome mediated degradation. the e3", "mediated degradation. the e3 ubiquitin", "degradation. the e3 ubiquitin ligase", "the e3 ubiquitin ligase mdm2", "ubiquitin ligase mdm2 which", "ligase mdm2 which is", "mdm2 which is a", "which is a transcriptional target", "is a transcriptional target of", "a transcriptional target of tp53", "target of tp53 plays", "of tp53 plays the", "tp53 plays the main", "plays the main role in", "the main role in tp53", "main role in tp53 protein", "role in tp53 protein down", "in tp53 protein down regulation", "protein down regulation wu", "down regulation wu et", "regulation wu et al.", "wu et al. 1993 .", "et al. 1993 . mdm2", "al. 1993 . mdm2 forms", "1993 . mdm2 forms homodimers", ". mdm2 forms homodimers and", "mdm2 forms homodimers and homo", "forms homodimers and homo oligomers", "and homo oligomers but", "homo oligomers but also", "oligomers but also functions", "but also functions as a", "also functions as a heterodimer/hetero", "functions as a heterodimer/hetero oligomer", "as a heterodimer/hetero oligomer with", "a heterodimer/hetero oligomer with mdm4", "oligomer with mdm4 mdmx", "mdmx sharp et", "et al. 1999 cheng", "al. 1999 cheng et", "1999 cheng et al.", "et al. 2011 huang", "al. 2011 huang et", "2011 huang et al.", "et al. 2011 pant", "al. 2011 pant et", "2011 pant et al.", "pant et al. 2011 .", "et al. 2011 . the", "al. 2011 . the heterodimers", "2011 . the heterodimers of", ". the heterodimers of mdm2", "the heterodimers of mdm2 and", "heterodimers of mdm2 and mdm4", "of mdm2 and mdm4 may", "mdm2 and mdm4 may be", "and mdm4 may be especially", "mdm4 may be especially important", "may be especially important for", "be especially important for downregulation", "especially important for downregulation of", "important for downregulation of tp53", "for downregulation of tp53 during", "downregulation of tp53 during embryonic", "of tp53 during embryonic development", "during embryonic development pant", "embryonic development pant et", "development pant et al.", "pant et al. 2011 .

the", "et al. 2011 .

the nuclear", "al. 2011 .

the nuclear localization", "2011 .

the nuclear localization of", ".

the nuclear localization of mdm2", "nuclear localization of mdm2 is", "localization of mdm2 is positively", "of mdm2 is positively regulated", "mdm2 is positively regulated by", "is positively regulated by akt", "regulated by akt or", "by akt or sgk1", "or sgk1 mediated phosphorylation", "mediated phosphorylation mayo and", "phosphorylation mayo and donner", "and donner 2001 zhou", "donner 2001 zhou et", "2001 zhou et al.", "et al. 2001 amato", "al. 2001 amato et", "2001 amato et al.", "et al. 2009 lyo", "al. 2009 lyo et", "2009 lyo et al.", "lyo et al. 2010 .", "et al. 2010 . phosphorylation", "al. 2010 . phosphorylation of", "2010 . phosphorylation of mdm2", ". phosphorylation of mdm2 by", "phosphorylation of mdm2 by cdk1", "of mdm2 by cdk1 or", "mdm2 by cdk1 or cdk2", "by cdk1 or cdk2 decreases", "cdk1 or cdk2 decreases affinity", "or cdk2 decreases affinity of", "cdk2 decreases affinity of mdm2", "decreases affinity of mdm2 for", "affinity of mdm2 for tp53", "mdm2 for tp53 zhang", "for tp53 zhang and", "tp53 zhang and prives", "zhang and prives 2001 .", "and prives 2001 . atm", "prives 2001 . atm and", "2001 . atm and chek2", ". atm and chek2 kinases", "and chek2 kinases activated", "chek2 kinases activated by", "kinases activated by double", "activated by double strand dna", "by double strand dna breaks", "strand dna breaks phosphorylate", "dna breaks phosphorylate tp53", "phosphorylate tp53 reducing its", "tp53 reducing its affinity", "reducing its affinity for mdm2", "affinity for mdm2 banin", "for mdm2 banin et", "mdm2 banin et al.", "et al. 1998 canman", "al. 1998 canman et", "1998 canman et al.", "et al. 1998 khanna", "al. 1998 khanna et", "1998 khanna et al.", "et al. 1998 chehab", "al. 1998 chehab et", "1998 chehab et al.", "et al. 1999 chehab", "al. 1999 chehab et", "1999 chehab et al.", "chehab et al. 2000 .", "et al. 2000 . at", "al. 2000 . at the", "2000 . at the same", ". at the same time", "the same time atm", "same time atm phosphorylates", "time atm phosphorylates mdm2", "atm phosphorylates mdm2 preventing", "phosphorylates mdm2 preventing mdm2", "mdm2 preventing mdm2 dimerization", "preventing mdm2 dimerization cheng", "mdm2 dimerization cheng et", "dimerization cheng et al.", "et al. 2009 cheng", "al. 2009 cheng et", "2009 cheng et al.", "cheng et al. 2011 .", "et al. 2011 . both", "al. 2011 . both atm", "2011 . both atm and", ". both atm and chek2", "both atm and chek2 phosphorylate", "atm and chek2 phosphorylate mdm4", "chek2 phosphorylate mdm4 triggering", "phosphorylate mdm4 triggering mdm2", "mdm4 triggering mdm2 mediated", "triggering mdm2 mediated ubiquitination of", "mdm2 mediated ubiquitination of mdm4", "ubiquitination of mdm4 chen", "of mdm4 chen et", "mdm4 chen et al.", "et al. 2005 pereg", "al. 2005 pereg et", "2005 pereg et al.", "pereg et al. 2005 .", "et al. 2005 . cyclin", "al. 2005 . cyclin g1", ". cyclin g1 ccng1", "ccng1 transcriptionally induced", "induced by tp53 targets", "by tp53 targets the", "tp53 targets the pp2a", "targets the pp2a phosphatase complex", "the pp2a phosphatase complex to", "pp2a phosphatase complex to mdm2", "complex to mdm2 resulting", "to mdm2 resulting in", "mdm2 resulting in dephosphorylation", "resulting in dephosphorylation of mdm2", "in dephosphorylation of mdm2 at", "dephosphorylation of mdm2 at specific", "of mdm2 at specific sites", "at specific sites which", "specific sites which can", "sites which can have", "which can have either a", "can have either a positive", "have either a positive or", "either a positive or a", "a positive or a negative", "positive or a negative impact", "or a negative impact on", "a negative impact on mdm2", "negative impact on mdm2 function", "on mdm2 function okamoto", "mdm2 function okamoto et", "function okamoto et al.", "okamoto et al. 2002 .

in", "et al. 2002 .

in contrast", "al. 2002 .

in contrast to", "2002 .

in contrast to mdm2", "contrast to mdm2 e3", "to mdm2 e3 ubiquitin", "mdm2 e3 ubiquitin ligases", "ubiquitin ligases rnf34 carp1", "rnf34 carp1 and", "rffl carp2 can", "carp2 can ubiquitinate phosphorylated", "ubiquitinate phosphorylated tp53 yang", "phosphorylated tp53 yang et", "tp53 yang et al.", "yang et al. 2007 .

in", "et al. 2007 .

in addition", "al. 2007 .

in addition to", "2007 .

in addition to ubiquitinating", ".

in addition to ubiquitinating mdm4", "to ubiquitinating mdm4 pereg", "ubiquitinating mdm4 pereg et", "mdm4 pereg et al.", "al. 2005 mdm2", "2005 mdm2 can", "mdm2 can also undergo auto", "can also undergo auto ubiquitination", "undergo auto ubiquitination fang", "auto ubiquitination fang et", "ubiquitination fang et al.", "fang et al. 2000 .", "et al. 2000 . mdm2", "al. 2000 . mdm2 and", "2000 . mdm2 and mdm4", ". mdm2 and mdm4 can", "mdm2 and mdm4 can be", "and mdm4 can be deubiquitinated", "mdm4 can be deubiquitinated by", "can be deubiquitinated by the", "be deubiquitinated by the ubiquitin", "deubiquitinated by the ubiquitin protease", "by the ubiquitin protease usp2", "ubiquitin protease usp2 stevenson", "protease usp2 stevenson et", "usp2 stevenson et al.", "et al. 2007 allende", "al. 2007 allende vega", "2007 allende vega et", "allende vega et al. 2010", "vega et al. 2010 .", "et al. 2010 . the", "al. 2010 . the ubiquitin", "2010 . the ubiquitin protease", ". the ubiquitin protease usp7", "the ubiquitin protease usp7 can", "ubiquitin protease usp7 can deubiquitinate", "protease usp7 can deubiquitinate tp53", "can deubiquitinate tp53 but", "deubiquitinate tp53 but in", "tp53 but in the", "but in the presence of", "in the presence of daxx", "the presence of daxx deubiquitinates", "presence of daxx deubiquitinates mdm2", "daxx deubiquitinates mdm2 li", "deubiquitinates mdm2 li et", "mdm2 li et al.", "et al. 2002 sheng", "al. 2002 sheng et", "2002 sheng et al.", "et al. 2006 tang", "al. 2006 tang et", "2006 tang et al.", "tang et al. 2006 .

the", "et al. 2006 .

the tumor", "al. 2006 .

the tumor suppressor", "2006 .

the tumor suppressor p14", ".

the tumor suppressor p14 arf", "suppressor p14 arf expressed", "p14 arf expressed from", "arf expressed from the", "expressed from the cdkn2a gene", "from the cdkn2a gene in", "the cdkn2a gene in response", "cdkn2a gene in response to", "gene in response to oncogenic", "in response to oncogenic or", "response to oncogenic or oxidative", "to oncogenic or oxidative stress", "or oxidative stress forms", "oxidative stress forms a", "stress forms a tripartite", "forms a tripartite complex with", "a tripartite complex with mdm2", "tripartite complex with mdm2 and", "complex with mdm2 and tp53", "mdm2 and tp53 sequesters", "and tp53 sequesters mdm2", "tp53 sequesters mdm2 from", "mdm2 from tp53 and", "from tp53 and thus", "tp53 and thus prevents", "and thus prevents tp53 degradation", "prevents tp53 degradation zhang", "tp53 degradation zhang et", "degradation zhang et al.", "et al. 1998 parisi", "al. 1998 parisi et", "1998 parisi et al.", "et al. 2002 voncken", "al. 2002 voncken et", "2002 voncken et al.", "voncken et al. 2005 .

for", "et al. 2005 .

for review", "al. 2005 .

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binding", ".

binding of", "of aspp", "aspp family", "family proteins", "proteins ppp1r13b", "or tp53bp2", "tp53 stimulates", "apoptotic tp53", "tp53 targets", "samuels lev", "lev et", "al. 2001", "bergamaschi et", "al. 2004", "2004 .", "the aspp", "family member", "member ppp1r13l", "inhibits tp53", "tp53 mediated", "mediated activation", "activation of", "genes probably", "probably by", "by interfering", "interfering with", "with binding", "of stimulatory", "stimulatory aspps", "aspps to", "al. 2003", "2003 .", ". transcription", "genes is", "is also", "also stimulated", "stimulated by", "by binding", "tp53 to", "to pou4f2", "budrham mahadeo", "al. 2006", "al. 2014", "or to", "to hcas/cse1l", "tanaka et", "2007 .

binding", "of co", "factors to", "tp53 can", "can also", "also affect", "affect protein", "protein stability.", "stability. for", "for example", "phf20 binds", "binds to", "tp53 dimethylated", "dimethylated on", "on lysine", "lysine residues", "residues k370", "k370 and", "and k382", "k382 by", "by unidentified", "unidentified protein", "protein lysine", "lysine methyltransferase", "methyltransferase s", "and interferes", "interferes with", "with mdm2", "mdm2 binding", "resulting in", "in prolonged", "prolonged tp53", "tp53 half", "half life", "cui et", "al. 2012", "2012 .", ". long", "long noncoding", "noncoding rnas", "rnas can", "can contribute", "contribute to", "to p53", "p53 dependent", "dependent transcriptional", "transcriptional responses", "huarte et", "al. 2010", "2010 .", ". for", "for a", "a general", "general review", "review on", "on this", "this topic", "see espinosa", "espinosa 2008", "beckerman and", "and prives", "prives 2010", "murray zmijewski", "zmijewski et", "al. 2008", "an et", "2004 and", "and barsotti", "barsotti and", "prives 2010.", "association of tp53", "tp53 p53", "p53 with", "with various transcriptional", "various transcriptional co", "transcriptional co factors", "co factors can", "factors can promote", "promote inhibit", "inhibit or provide", "or provide specificity", "provide specificity towards", "specificity towards either", "towards either transcription", "either transcription of", "transcription of cell", "of cell cycle", "cell cycle arrest", "cycle arrest genes", "arrest genes or", "genes or transcription", "or transcription of", "of cell death", "cell death genes.", "death genes. binding", "genes. binding of", "binding of the", "of the zinc", "the zinc finger", "zinc finger protein", "finger protein znf385a", "znf385a hzf", "which is a", "is a transcriptional", "a transcriptional target", "transcriptional target of", "target of tp53", "stimulates transcription of", "genes such", "such as cdkn1a", "cdkn1a das", "das et al.", "et al. 2007", "al. 2007 .", "2007 . binding", ". binding of", "binding of pou4f1", "pou4f1 brn3a", "brn3a to", "to tp53 also", "tp53 also stimulates", "also stimulates transcription", "arrest genes while", "genes while inhibiting", "while inhibiting transcription", "inhibiting transcription of", "transcription of pro", "of pro apoptotic", "pro apoptotic genes", "genes budhram", "budhram mahadeo et", "mahadeo et al.", "et al. 1999", "1999 hudson", "hudson et al.", "et al. 2005", "al. 2005 .

binding", "2005 .

binding of", ".

binding of aspp", "of aspp family", "aspp family proteins", "family proteins ppp1r13b", "ppp1r13b aspp1", "aspp1 or", "tp53bp2 aspp2", "aspp2 to", "to tp53 stimulates", "tp53 stimulates transcription", "pro apoptotic tp53", "apoptotic tp53 targets", "targets samuels", "samuels lev et", "lev et al.", "et al. 2001", "2001 bergamaschi", "bergamaschi et al.", "et al. 2004", "al. 2004 .", "2004 . binding", "of the aspp", "the aspp family", "aspp family member", "family member ppp1r13l", "ppp1r13l iassp", "iassp inhibits", "inhibits tp53 mediated", "tp53 mediated activation", "mediated activation of", "activation of pro", "apoptotic genes probably", "genes probably by", "probably by interfering", "by interfering with", "interfering with binding", "with binding of", "binding of stimulatory", "of stimulatory aspps", "stimulatory aspps to", "aspps to tp53", "tp53 bergamaschi", "et al. 2003", "al. 2003 .", "2003 . transcription", ". transcription of", "apoptotic genes is", "genes is also", "is also stimulated", "also stimulated by", "stimulated by binding", "by binding of", "binding of tp53", "of tp53 to", "tp53 to pou4f2", "pou4f2 brn3b", "budrham mahadeo et", "et al. 2006", "2006 budhram", "et al. 2014", "2014 or", "or to hcas/cse1l", "hcas/cse1l tanaka", "tanaka et al.", "al. 2007 .

binding", "2007 .

binding of", ".

binding of co", "of co factors", "co factors to", "factors to tp53", "to tp53 can", "tp53 can also", "can also affect", "also affect protein", "affect protein stability.", "protein stability. for", "stability. for example", "example phf20", "phf20 binds to", "binds to tp53", "to tp53 dimethylated", "tp53 dimethylated on", "dimethylated on lysine", "on lysine residues", "lysine residues k370", "residues k370 and", "k370 and k382", "and k382 by", "k382 by unidentified", "by unidentified protein", "unidentified protein lysine", "protein lysine methyltransferase", "lysine methyltransferase s", "s and", "and interferes with", "interferes with mdm2", "with mdm2 binding", "binding resulting", "resulting in prolonged", "in prolonged tp53", "prolonged tp53 half", "tp53 half life", "life cui", "cui et al.", "et al. 2012", "al. 2012 .", "2012 . long", ". long noncoding", "long noncoding rnas", "noncoding rnas can", "rnas can contribute", "can contribute to", "contribute to p53", "to p53 dependent", "p53 dependent transcriptional", "dependent transcriptional responses", "responses huarte", "huarte et al.", "et al. 2010", "al. 2010 .", "2010 . for", ". for a", "for a general", "a general review", "general review on", "review on this", "on this topic", "topic see", "see espinosa 2008", "2008 beckerman", "beckerman and prives", "and prives 2010", "2010 murray", "murray zmijewski et", "zmijewski et al.", "et al. 2008", "2008 an", "an et al.", "al. 2004 and", "2004 and barsotti", "and barsotti and", "barsotti and prives", "and prives 2010.", "of tp53 p53", "p53 with various", "with various transcriptional co", "various transcriptional co factors", "transcriptional co factors can", "co factors can promote", "can promote inhibit", "promote inhibit or", "inhibit or provide specificity", "or provide specificity towards", "provide specificity towards either", "specificity towards either transcription", "towards either transcription of", "either transcription of cell", "transcription of cell cycle", "of cell cycle arrest", "cell cycle arrest genes", "cycle arrest genes or", "arrest genes or transcription", "genes or transcription of", "or transcription of cell", "transcription of cell death", "of cell death genes.", "cell death genes. binding", "death genes. binding of", "genes. binding of the", "binding of the zinc", "of the zinc finger", "the zinc finger protein", "zinc finger protein znf385a", "protein znf385a hzf", "hzf which", "which is a transcriptional", "is a transcriptional target", "a transcriptional target of", "transcriptional target of tp53", "of tp53 stimulates", "stimulates transcription of cell", "arrest genes such", "genes such as", "as cdkn1a das", "cdkn1a das et", "das et al. 2007", "et al. 2007 .", "al. 2007 . binding", "2007 . binding of", ". binding of pou4f1", "of pou4f1 brn3a", "brn3a to tp53", "to tp53 also stimulates", "tp53 also stimulates transcription", "also stimulates transcription of", "cycle arrest genes while", "arrest genes while inhibiting", "genes while inhibiting transcription", "while inhibiting transcription of", "inhibiting transcription of pro", "transcription of pro apoptotic", "of pro apoptotic genes", "apoptotic genes budhram", "genes budhram mahadeo", "budhram mahadeo et al.", "mahadeo et al. 1999", "al. 1999 hudson", "1999 hudson et", "hudson et al. 2005", "et al. 2005 .

binding", "al. 2005 .

binding of", "2005 .

binding of aspp", ".

binding of aspp family", "of aspp family proteins", "aspp family proteins ppp1r13b", "proteins ppp1r13b aspp1", "aspp1 or tp53bp2", "or tp53bp2 aspp2", "aspp2 to tp53", "to tp53 stimulates transcription", "tp53 stimulates transcription of", "stimulates transcription of pro", "of pro apoptotic tp53", "pro apoptotic tp53 targets", "tp53 targets samuels", "targets samuels lev", "samuels lev et al.", "lev et al. 2001", "al. 2001 bergamaschi", "2001 bergamaschi et", "bergamaschi et al. 2004", "et al. 2004 .", "al. 2004 . binding", "2004 . binding of", ". binding of the", "binding of the aspp", "of the aspp family", "the aspp family member", "aspp family member ppp1r13l", "member ppp1r13l iassp", "iassp inhibits tp53", "inhibits tp53 mediated activation", "tp53 mediated activation of", "mediated activation of pro", "activation of pro apoptotic", "pro apoptotic genes probably", "apoptotic genes probably by", "genes probably by interfering", "probably by interfering with", "by interfering with binding", "interfering with binding of", "with binding of stimulatory", "binding of stimulatory aspps", "of stimulatory aspps to", "stimulatory aspps to tp53", "to tp53 bergamaschi", "tp53 bergamaschi et", "bergamaschi et al. 2003", "et al. 2003 .", "al. 2003 . transcription", "2003 . transcription of", ". transcription of pro", "pro apoptotic genes is", "apoptotic genes is also", "genes is also stimulated", "is also stimulated by", "also stimulated by binding", "stimulated by binding of", "by binding of tp53", "binding of tp53 to", "of tp53 to pou4f2", "to pou4f2 brn3b", "brn3b budrham", "budrham mahadeo et al.", "mahadeo et al. 2006", "al. 2006 budhram", "2006 budhram mahadeo", "mahadeo et al. 2014", "al. 2014 or", "2014 or to", "to hcas/cse1l tanaka", "hcas/cse1l tanaka et", "tanaka et al. 2007", "et al. 2007 .

binding", "al. 2007 .

binding of", "2007 .

binding of co", ".

binding of co factors", "of co factors to", "co factors to tp53", "factors to tp53 can", "to tp53 can also", "tp53 can also affect", "can also affect protein", "also affect protein stability.", "affect protein stability. for", "protein stability. for example", "for example phf20", "example phf20 binds", "phf20 binds to tp53", "binds to tp53 dimethylated", "to tp53 dimethylated on", "tp53 dimethylated on lysine", "dimethylated on lysine residues", "on lysine residues k370", "lysine residues k370 and", "residues k370 and k382", "k370 and k382 by", "and k382 by unidentified", "k382 by unidentified protein", "by unidentified protein lysine", "unidentified protein lysine methyltransferase", "protein lysine methyltransferase s", "methyltransferase s and", "s and interferes", "and interferes with mdm2", "interferes with mdm2 binding", "mdm2 binding resulting", "binding resulting in", "resulting in prolonged tp53", "in prolonged tp53 half", "prolonged tp53 half life", "half life cui", "life cui et", "cui et al. 2012", "et al. 2012 .", "al. 2012 . long", "2012 . long noncoding", ". long noncoding rnas", "long noncoding rnas can", "noncoding rnas can contribute", "rnas can contribute to", "can contribute to p53", "contribute to p53 dependent", "to p53 dependent transcriptional", "p53 dependent transcriptional responses", "transcriptional responses huarte", "responses huarte et", "huarte et al. 2010", "et al. 2010 .", "al. 2010 . for", "2010 . for a", ". for a general", "for a general review", "a general review on", "general review on this", "review on this topic", "this topic see", "topic see espinosa", "espinosa 2008 beckerman", "2008 beckerman and", "beckerman and prives 2010", "prives 2010 murray", "2010 murray zmijewski", "murray zmijewski et al.", "zmijewski et al. 2008", "al. 2008 an", "2008 an et", "an et al. 2004", "et al. 2004 and", "al. 2004 and barsotti", "2004 and barsotti and", "and barsotti and prives", "barsotti and prives 2010.", "association of tp53 p53", "tp53 p53 with", "p53 with various transcriptional", "with various transcriptional co factors", "various transcriptional co factors can", "transcriptional co factors can promote", "factors can promote inhibit", "can promote inhibit or", "promote inhibit or provide", "inhibit or provide specificity towards", "or provide specificity towards either", "provide specificity towards either transcription", "specificity towards either transcription of", "towards either transcription of cell", "either transcription of cell cycle", "transcription of cell cycle arrest", "of cell cycle arrest genes", "cell cycle arrest genes or", "cycle arrest genes or transcription", "arrest genes or transcription of", "genes or transcription of cell", "or transcription of cell death", "transcription of cell death genes.", "of cell death genes. binding", "cell death genes. binding of", "death genes. binding of the", "genes. binding of the zinc", "binding of the zinc finger", "of the zinc finger protein", "the zinc finger protein znf385a", "finger protein znf385a hzf", "hzf which is", "which is a transcriptional target", "is a transcriptional target of", "a transcriptional target of tp53", "target of tp53 stimulates", "of tp53 stimulates transcription", "stimulates transcription of cell cycle", "cycle arrest genes such", "arrest genes such as", "genes such as cdkn1a", "such as cdkn1a das", "as cdkn1a das et", "cdkn1a das et al.", "das et al. 2007 .", "et al. 2007 . binding", "al. 2007 . binding of", "2007 . binding of pou4f1", "binding of pou4f1 brn3a", "pou4f1 brn3a to", "brn3a to tp53 also", "to tp53 also stimulates transcription", "tp53 also stimulates transcription of", "also stimulates transcription of cell", "cell cycle arrest genes while", "cycle arrest genes while inhibiting", "arrest genes while inhibiting transcription", "genes while inhibiting transcription of", "while inhibiting transcription of pro", "inhibiting transcription of pro apoptotic", "transcription of pro apoptotic genes", "pro apoptotic genes budhram", "apoptotic genes budhram mahadeo", "genes budhram mahadeo et", "budhram mahadeo et al. 1999", "et al. 1999 hudson", "al. 1999 hudson et", "1999 hudson et al.", "hudson et al. 2005 .

binding", "et al. 2005 .

binding of", "al. 2005 .

binding of aspp", "2005 .

binding of aspp family", ".

binding of aspp family proteins", "of aspp family proteins ppp1r13b", "family proteins ppp1r13b aspp1", "ppp1r13b aspp1 or", "tp53bp2 aspp2 to", "aspp2 to tp53 stimulates", "to tp53 stimulates transcription of", "tp53 stimulates transcription of pro", "stimulates transcription of pro apoptotic", "transcription of pro apoptotic tp53", "of pro apoptotic tp53 targets", "apoptotic tp53 targets samuels", "tp53 targets samuels lev", "targets samuels lev et", "samuels lev et al. 2001", "et al. 2001 bergamaschi", "al. 2001 bergamaschi et", "2001 bergamaschi et al.", "bergamaschi et al. 2004 .", "et al. 2004 . binding", "al. 2004 . binding of", "2004 . binding of the", ". binding of the aspp", "binding of the aspp family", "of the aspp family member", "the aspp family member ppp1r13l", "family member ppp1r13l iassp", "ppp1r13l iassp inhibits", "iassp inhibits tp53 mediated", "inhibits tp53 mediated activation of", "tp53 mediated activation of pro", "mediated activation of pro apoptotic", "activation of pro apoptotic genes", "of pro apoptotic genes probably", "pro apoptotic genes probably by", "apoptotic genes probably by interfering", "genes probably by interfering with", "probably by interfering with binding", "by interfering with binding of", "interfering with binding of stimulatory", "with binding of stimulatory aspps", "binding of stimulatory aspps to", "of stimulatory aspps to tp53", "aspps to tp53 bergamaschi", "to tp53 bergamaschi et", "tp53 bergamaschi et al.", "bergamaschi et al. 2003 .", "et al. 2003 . transcription", "al. 2003 . transcription of", "2003 . transcription of pro", ". transcription of pro apoptotic", "of pro apoptotic genes is", "pro apoptotic genes is also", "apoptotic genes is also stimulated", "genes is also stimulated by", "is also stimulated by binding", "also stimulated by binding of", "stimulated by binding of tp53", "by binding of tp53 to", "binding of tp53 to pou4f2", "tp53 to pou4f2 brn3b", "brn3b budrham mahadeo", "budrham mahadeo et al. 2006", "et al. 2006 budhram", "al. 2006 budhram mahadeo", "2006 budhram mahadeo et", "budhram mahadeo et al. 2014", "et al. 2014 or", "al. 2014 or to", "2014 or to hcas/cse1l", "or to hcas/cse1l tanaka", "to hcas/cse1l tanaka et", "hcas/cse1l tanaka et al.", "tanaka et al. 2007 .

binding", "et al. 2007 .

binding of", "al. 2007 .

binding of co", "2007 .

binding of co factors", ".

binding of co factors to", "of co factors to tp53", "co factors to tp53 can", "factors to tp53 can also", "to tp53 can also affect", "tp53 can also affect protein", "can also affect protein stability.", "also affect protein stability. for", "affect protein stability. for example", "stability. for example phf20", "for example phf20 binds", "example phf20 binds to", "phf20 binds to tp53 dimethylated", "binds to tp53 dimethylated on", "to tp53 dimethylated on lysine", "tp53 dimethylated on lysine residues", "dimethylated on lysine residues k370", "on lysine residues k370 and", "lysine residues k370 and k382", "residues k370 and k382 by", "k370 and k382 by unidentified", "and k382 by unidentified protein", "k382 by unidentified protein lysine", "by unidentified protein lysine methyltransferase", "unidentified protein lysine methyltransferase s", "lysine methyltransferase s and", "methyltransferase s and interferes", "s and interferes with", "and interferes with mdm2 binding", "with mdm2 binding resulting", "mdm2 binding resulting in", "binding resulting in prolonged", "resulting in prolonged tp53 half", "in prolonged tp53 half life", "tp53 half life cui", "half life cui et", "life cui et al.", "cui et al. 2012 .", "et al. 2012 . long", "al. 2012 . long noncoding", "2012 . long noncoding rnas", ". long noncoding rnas can", "long noncoding rnas can contribute", "noncoding rnas can contribute to", "rnas can contribute to p53", "can contribute to p53 dependent", "contribute to p53 dependent transcriptional", "to p53 dependent transcriptional responses", "dependent transcriptional responses huarte", "transcriptional responses huarte et", "responses huarte et al.", "huarte et al. 2010 .", "et al. 2010 . for", "al. 2010 . for a", "2010 . for a general", ". for a general review", "for a general review on", "a general review on this", "general review on this topic", "on this topic see", "this topic see espinosa", "topic see espinosa 2008", "see espinosa 2008 beckerman", "espinosa 2008 beckerman and", "2008 beckerman and prives", "and prives 2010 murray", "prives 2010 murray zmijewski", "2010 murray zmijewski et", "murray zmijewski et al. 2008", "et al. 2008 an", "al. 2008 an et", "2008 an et al.", "an et al. 2004 and", "et al. 2004 and barsotti", "al. 2004 and barsotti and", "2004 and barsotti and prives", "and barsotti and prives 2010." ] }, { "record_id": "GLY_000594_1_533", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6804760", "r hsa", "hsa 6804760", "r hsa 6804760" ] }, { "record_id": "GLY_000594_1_533", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of tp53", "tp53 activity", "activity through", "through methylation", "regulation of tp53", "of tp53 activity", "tp53 activity through", "activity through methylation", "regulation of tp53 activity", "of tp53 activity through", "tp53 activity through methylation", "regulation of tp53 activity through", "of tp53 activity through methylation", "undergoes methylation", "methylation on", "on several", "several lysine", "lysine and", "and arginine", "arginine residues", "which modulates", "modulates its", "its transcriptional", "transcriptional activity.

prmt5", "recruited to", "to tp53", "tp53 as", "as part", "part of", "of the", "the atm", "atm activated", "activated complex", "complex that", "that includes", "includes ttc5", "jmy and", "and ep300", "methylates tp53", "tp53 arginine", "residues r333", "r335 and", "and r337.", "r337. prmt5", "prmt5 mediated", "mediated methylation", "methylation promotes", "promotes tp53", "tp53 stimulated", "stimulated expression", "expression of", "of cell", "cell cycle", "cycle arrest", "arrest genes", "shikama et", "et al.", "al. 1999", "demonacos et", "al. 2001", "al. 2004", "adams et", "al. 2008", "al. 2012", "2012 .", ". setd9", "tp53 at", "at lysine", "lysine residue", "residue k372", "resulting in", "in increased", "increased stability", "stability and", "and activity", "activity of", "chuikov et", "couture et", "al. 2006", "bai et", "al. 2011", "2011 .

tp53", ".

tp53 transcriptional", "transcriptional activity", "activity is", "is repressed", "repressed by", "by smyd2", "smyd2 mediated", "methylation of", "residue k370", "huang et", "2006 .", ". dimethylation", "dimethylation of", "residue k373", "k373 by", "by the", "the complex", "complex of", "of methyltransferases", "methyltransferases ehmt1", "ehmt1 and", "and ehmt2", "ehmt2 also", "also represses", "represses tp53", "tp53 mediated", "mediated transcription", "al. 2010", "2010 .", ". the", "the chromatin", "chromatin compaction", "compaction factor", "factor l3mbtl1", "l3mbtl1 binds", "binds tp53", "tp53 monomethylated", "monomethylated at", "lysine k382", "k382 by", "by setd8", "probably through", "through changing", "changing local", "local chromatin", "chromatin architecture", "represses transcription", "transcription of", "tp53 targets", "west et", "the histone", "histone lysine", "lysine specific", "specific demethylase", "demethylase lsd1", "lsd1 interacts", "interacts with", "with tp53", "tp53 and", "and represses", "represses p53", "p53 mediated", "mediated transcriptional", "transcriptional activation", "al. 2007", "2007 .", ". prmt1", "prmt1 and", "and carm1", "carm1 can", "can also", "also modulate", "modulate p53", "p53 functions", "functions in", "in a", "a cooperative", "cooperative manner", "an et", "2004 .", "tp53 p53", "p53 undergoes", "undergoes methylation on", "methylation on several", "on several lysine", "several lysine and", "lysine and arginine", "and arginine residues", "residues which", "which modulates its", "modulates its transcriptional", "its transcriptional activity.

prmt5", "activity.

prmt5 recruited", "recruited to tp53", "to tp53 as", "tp53 as part", "as part of", "part of the", "of the atm", "the atm activated", "atm activated complex", "activated complex that", "complex that includes", "that includes ttc5", "ttc5 jmy", "jmy and ep300", "ep300 p300", "methylates tp53 arginine", "tp53 arginine residues", "arginine residues r333", "r333 r335", "r335 and r337.", "and r337. prmt5", "r337. prmt5 mediated", "prmt5 mediated methylation", "mediated methylation promotes", "methylation promotes tp53", "promotes tp53 stimulated", "tp53 stimulated expression", "stimulated expression of", "expression of cell", "of cell cycle", "cell cycle arrest", "cycle arrest genes", "genes shikama", "shikama et al.", "et al. 1999", "1999 demonacos", "demonacos et al.", "et al. 2001", "2001 demonacos", "et al. 2004", "2004 adams", "adams et al.", "et al. 2008", "2008 adams", "et al. 2012", "al. 2012 .", "2012 . setd9", "setd9 set9", "set9 methylates", "methylates tp53 at", "tp53 at lysine", "at lysine residue", "lysine residue k372", "k372 resulting", "resulting in increased", "in increased stability", "increased stability and", "stability and activity", "and activity of", "activity of tp53", "tp53 chuikov", "chuikov et al.", "2004 couture", "couture et al.", "et al. 2006", "2006 bai", "bai et al.", "et al. 2011", "al. 2011 .

tp53", "2011 .

tp53 transcriptional", ".

tp53 transcriptional activity", "transcriptional activity is", "activity is repressed", "is repressed by", "repressed by smyd2", "by smyd2 mediated", "smyd2 mediated methylation", "mediated methylation of", "methylation of tp53", "of tp53 at", "lysine residue k370", "k370 huang", "huang et al.", "al. 2006 .", "2006 . dimethylation", ". dimethylation of", "dimethylation of tp53", "lysine residue k373", "residue k373 by", "k373 by the", "by the complex", "the complex of", "complex of methyltransferases", "of methyltransferases ehmt1", "methyltransferases ehmt1 and", "ehmt1 and ehmt2", "and ehmt2 also", "ehmt2 also represses", "also represses tp53", "represses tp53 mediated", "tp53 mediated transcription", "transcription huang", "et al. 2010", "al. 2010 .", "2010 . the", ". the chromatin", "the chromatin compaction", "chromatin compaction factor", "compaction factor l3mbtl1", "factor l3mbtl1 binds", "l3mbtl1 binds tp53", "binds tp53 monomethylated", "tp53 monomethylated at", "monomethylated at lysine", "at lysine k382", "lysine k382 by", "k382 by setd8", "setd8 set8", "set8 and", "and probably", "probably through changing", "through changing local", "changing local chromatin", "local chromatin architecture", "architecture represses", "represses transcription of", "transcription of tp53", "of tp53 targets", "targets west", "west et al.", ". the histone", "the histone lysine", "histone lysine specific", "lysine specific demethylase", "specific demethylase lsd1", "demethylase lsd1 interacts", "lsd1 interacts with", "interacts with tp53", "with tp53 and", "tp53 and represses", "and represses p53", "represses p53 mediated", "p53 mediated transcriptional", "mediated transcriptional activation", "activation huang", "et al. 2007", "al. 2007 .", "2007 . prmt1", ". prmt1 and", "prmt1 and carm1", "and carm1 can", "carm1 can also", "can also modulate", "also modulate p53", "modulate p53 functions", "p53 functions in", "functions in a", "in a cooperative", "a cooperative manner", "manner an", "an et al.", "al. 2004 .", "p53 undergoes methylation", "undergoes methylation on several", "methylation on several lysine", "on several lysine and", "several lysine and arginine", "lysine and arginine residues", "arginine residues which", "residues which modulates", "which modulates its transcriptional", "modulates its transcriptional activity.

prmt5", "transcriptional activity.

prmt5 recruited", "activity.

prmt5 recruited to", "recruited to tp53 as", "to tp53 as part", "tp53 as part of", "as part of the", "part of the atm", "of the atm activated", "the atm activated complex", "atm activated complex that", "activated complex that includes", "complex that includes ttc5", "includes ttc5 jmy", "ttc5 jmy and", "and ep300 p300", "p300 methylates", "methylates tp53 arginine residues", "tp53 arginine residues r333", "residues r333 r335", "r333 r335 and", "r335 and r337. prmt5", "and r337. prmt5 mediated", "r337. prmt5 mediated methylation", "prmt5 mediated methylation promotes", "mediated methylation promotes tp53", "methylation promotes tp53 stimulated", "promotes tp53 stimulated expression", "tp53 stimulated expression of", "stimulated expression of cell", "expression of cell cycle", "of cell cycle arrest", "cell cycle arrest genes", "arrest genes shikama", "genes shikama et", "shikama et al. 1999", "al. 1999 demonacos", "1999 demonacos et", "demonacos et al. 2001", "al. 2001 demonacos", "2001 demonacos et", "demonacos et al. 2004", "al. 2004 adams", "2004 adams et", "adams et al. 2008", "al. 2008 adams", "2008 adams et", "adams et al. 2012", "et al. 2012 .", "al. 2012 . setd9", ". setd9 set9", "set9 methylates tp53", "methylates tp53 at lysine", "tp53 at lysine residue", "at lysine residue k372", "residue k372 resulting", "k372 resulting in", "resulting in increased stability", "in increased stability and", "increased stability and activity", "stability and activity of", "and activity of tp53", "of tp53 chuikov", "tp53 chuikov et", "chuikov et al. 2004", "al. 2004 couture", "2004 couture et", "couture et al. 2006", "al. 2006 bai", "2006 bai et", "bai et al. 2011", "et al. 2011 .

tp53", "al. 2011 .

tp53 transcriptional", "2011 .

tp53 transcriptional activity", ".

tp53 transcriptional activity is", "transcriptional activity is repressed", "activity is repressed by", "is repressed by smyd2", "repressed by smyd2 mediated", "by smyd2 mediated methylation", "smyd2 mediated methylation of", "mediated methylation of tp53", "methylation of tp53 at", "of tp53 at lysine", "at lysine residue k370", "residue k370 huang", "k370 huang et", "huang et al. 2006", "et al. 2006 .", "al. 2006 . dimethylation", "2006 . dimethylation of", ". dimethylation of tp53", "dimethylation of tp53 at", "at lysine residue k373", "lysine residue k373 by", "residue k373 by the", "k373 by the complex", "by the complex of", "the complex of methyltransferases", "complex of methyltransferases ehmt1", "of methyltransferases ehmt1 and", "methyltransferases ehmt1 and ehmt2", "ehmt1 and ehmt2 also", "and ehmt2 also represses", "ehmt2 also represses tp53", "also represses tp53 mediated", "represses tp53 mediated transcription", "mediated transcription huang", "transcription huang et", "huang et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the chromatin", ". the chromatin compaction", "the chromatin compaction factor", "chromatin compaction factor l3mbtl1", "compaction factor l3mbtl1 binds", "factor l3mbtl1 binds tp53", "l3mbtl1 binds tp53 monomethylated", "binds tp53 monomethylated at", "tp53 monomethylated at lysine", "monomethylated at lysine k382", "at lysine k382 by", "lysine k382 by setd8", "by setd8 set8", "and probably through", "probably through changing local", "through changing local chromatin", "changing local chromatin architecture", "chromatin architecture represses", "architecture represses transcription", "represses transcription of tp53", "transcription of tp53 targets", "tp53 targets west", "targets west et", "west et al. 2010", "2010 . the histone", ". the histone lysine", "the histone lysine specific", "histone lysine specific demethylase", "lysine specific demethylase lsd1", "specific demethylase lsd1 interacts", "demethylase lsd1 interacts with", "lsd1 interacts with tp53", "interacts with tp53 and", "with tp53 and represses", "tp53 and represses p53", "and represses p53 mediated", "represses p53 mediated transcriptional", "p53 mediated transcriptional activation", "transcriptional activation huang", "activation huang et", "huang et al. 2007", "et al. 2007 .", "al. 2007 . prmt1", "2007 . prmt1 and", ". prmt1 and carm1", "prmt1 and carm1 can", "and carm1 can also", "carm1 can also modulate", "can also modulate p53", "also modulate p53 functions", "modulate p53 functions in", "p53 functions in a", "functions in a cooperative", "in a cooperative manner", "cooperative manner an", "manner an et", "an et al. 2004", "et al. 2004 .", "tp53 p53 undergoes", "p53 undergoes methylation on", "undergoes methylation on several lysine", "methylation on several lysine and", "on several lysine and arginine", "several lysine and arginine residues", "and arginine residues which", "arginine residues which modulates", "residues which modulates its", "which modulates its transcriptional activity.

prmt5", "its transcriptional activity.

prmt5 recruited", "transcriptional activity.

prmt5 recruited to", "activity.

prmt5 recruited to tp53", "recruited to tp53 as part", "to tp53 as part of", "tp53 as part of the", "as part of the atm", "part of the atm activated", "of the atm activated complex", "the atm activated complex that", "atm activated complex that includes", "activated complex that includes ttc5", "that includes ttc5 jmy", "includes ttc5 jmy and", "ttc5 jmy and ep300", "jmy and ep300 p300", "p300 methylates tp53", "methylates tp53 arginine residues r333", "arginine residues r333 r335", "residues r333 r335 and", "r333 r335 and r337.", "r335 and r337. prmt5 mediated", "and r337. prmt5 mediated methylation", "r337. prmt5 mediated methylation promotes", "prmt5 mediated methylation promotes tp53", "mediated methylation promotes tp53 stimulated", "methylation promotes tp53 stimulated expression", "promotes tp53 stimulated expression of", "tp53 stimulated expression of cell", "stimulated expression of cell cycle", "expression of cell cycle arrest", "of cell cycle arrest genes", "cycle arrest genes shikama", "arrest genes shikama et", "genes shikama et al.", "et al. 1999 demonacos", "al. 1999 demonacos et", "1999 demonacos et al.", "et al. 2001 demonacos", "al. 2001 demonacos et", "2001 demonacos et al.", "et al. 2004 adams", "al. 2004 adams et", "2004 adams et al.", "et al. 2008 adams", "al. 2008 adams et", "2008 adams et al.", "adams et al. 2012 .", "et al. 2012 . setd9", "2012 . setd9 set9", "setd9 set9 methylates", "set9 methylates tp53 at", "methylates tp53 at lysine residue", "tp53 at lysine residue k372", "lysine residue k372 resulting", "residue k372 resulting in", "k372 resulting in increased", "resulting in increased stability and", "in increased stability and activity", "increased stability and activity of", "stability and activity of tp53", "activity of tp53 chuikov", "of tp53 chuikov et", "tp53 chuikov et al.", "et al. 2004 couture", "al. 2004 couture et", "2004 couture et al.", "et al. 2006 bai", "al. 2006 bai et", "2006 bai et al.", "bai et al. 2011 .

tp53", "et al. 2011 .

tp53 transcriptional", "al. 2011 .

tp53 transcriptional activity", "2011 .

tp53 transcriptional activity is", ".

tp53 transcriptional activity is repressed", "transcriptional activity is repressed by", "activity is repressed by smyd2", "is repressed by smyd2 mediated", "repressed by smyd2 mediated methylation", "by smyd2 mediated methylation of", "smyd2 mediated methylation of tp53", "mediated methylation of tp53 at", "methylation of tp53 at lysine", "of tp53 at lysine residue", "tp53 at lysine residue k370", "lysine residue k370 huang", "residue k370 huang et", "k370 huang et al.", "huang et al. 2006 .", "et al. 2006 . dimethylation", "al. 2006 . dimethylation of", "2006 . dimethylation of tp53", ". dimethylation of tp53 at", "dimethylation of tp53 at lysine", "tp53 at lysine residue k373", "at lysine residue k373 by", "lysine residue k373 by the", "residue k373 by the complex", "k373 by the complex of", "by the complex of methyltransferases", "the complex of methyltransferases ehmt1", "complex of methyltransferases ehmt1 and", "of methyltransferases ehmt1 and ehmt2", "methyltransferases ehmt1 and ehmt2 also", "ehmt1 and ehmt2 also represses", "and ehmt2 also represses tp53", "ehmt2 also represses tp53 mediated", "also represses tp53 mediated transcription", "tp53 mediated transcription huang", "mediated transcription huang et", "transcription huang et al.", "huang et al. 2010 .", "et al. 2010 . the", "al. 2010 . the chromatin", "2010 . the chromatin compaction", ". the chromatin compaction factor", "the chromatin compaction factor l3mbtl1", "chromatin compaction factor l3mbtl1 binds", "compaction factor l3mbtl1 binds tp53", "factor l3mbtl1 binds tp53 monomethylated", "l3mbtl1 binds tp53 monomethylated at", "binds tp53 monomethylated at lysine", "tp53 monomethylated at lysine k382", "monomethylated at lysine k382 by", "at lysine k382 by setd8", "k382 by setd8 set8", "setd8 set8 and", "set8 and probably", "and probably through changing", "probably through changing local chromatin", "through changing local chromatin architecture", "local chromatin architecture represses", "chromatin architecture represses transcription", "architecture represses transcription of", "represses transcription of tp53 targets", "of tp53 targets west", "tp53 targets west et", "targets west et al.", "west et al. 2010 .", "al. 2010 . the histone", "2010 . the histone lysine", ". the histone lysine specific", "the histone lysine specific demethylase", "histone lysine specific demethylase lsd1", "lysine specific demethylase lsd1 interacts", "specific demethylase lsd1 interacts with", "demethylase lsd1 interacts with tp53", "lsd1 interacts with tp53 and", "interacts with tp53 and represses", "with tp53 and represses p53", "tp53 and represses p53 mediated", "and represses p53 mediated transcriptional", "represses p53 mediated transcriptional activation", "mediated transcriptional activation huang", "transcriptional activation huang et", "activation huang et al.", "huang et al. 2007 .", "et al. 2007 . prmt1", "al. 2007 . prmt1 and", "2007 . prmt1 and carm1", ". prmt1 and carm1 can", "prmt1 and carm1 can also", "and carm1 can also modulate", "carm1 can also modulate p53", "can also modulate p53 functions", "also modulate p53 functions in", "modulate p53 functions in a", "p53 functions in a cooperative", "functions in a cooperative manner", "a cooperative manner an", "cooperative manner an et", "manner an et al.", "an et al. 2004 ." ] }, { "record_id": "GLY_000594_1_534", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6805567", "r hsa", "hsa 6805567", "r hsa 6805567" ] }, { "record_id": "GLY_000594_1_534", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "keratins are", "are the", "the major", "major structural", "structural protein", "protein of", "of vertebrate", "vertebrate epidermis", "constituting up", "up to", "to 85%", "85% of", "of a", "a fully", "fully differentiated", "differentiated keratinocyte", "fuchs 1995", "1995 .", ". keratins", "keratins belong", "belong 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acidic type", "acidic type i", "type i and", "i and basic", "and basic /neutral", "basic /neutral type", "/neutral type 2", "type 2 keratins.", "2 keratins. humans", "keratins. humans have", "humans have 54", "have 54 keratin", "54 keratin genes", "genes schweitzer", "schweitzer et al.", "et al. 2006", "al. 2006 .", "2006 . they", ". they have", "they have highly", "have highly specific", "highly specific expression", "specific expression patterns", "patterns related", "related to the", "to the epithelial", "the epithelial type", "epithelial type and", "type and stage", "and stage of", "stage of differentiation.", "of differentiation. roughly", "differentiation. roughly half", "roughly half of", "half of human", "of human keratins", "human keratins are", "keratins are specific", "are specific to", "specific to hair", "to hair follicles", "follicles langbein", "langbein & schweizer", "& schweizer 2005", "schweizer 2005 .", "2005 . keratin", ". keratin filaments", "keratin filaments bundle", "filaments bundle into", "bundle into tonofilaments", "into tonofilaments that", "tonofilaments that span", "that span the", "span the cytoplasm", "the cytoplasm and", "cytoplasm and bind", "and bind to", "bind to desmosomes", "to desmosomes and", "desmosomes and other", "and other cell", "other cell membrane", "cell membrane structures", "structures waschke", "waschke 2008 .", "2008 . this", ". this reflects", "this reflects their", "reflects their primary", "their primary function", "function maintaining", "maintaining the mechanical", "the mechanical stability", "mechanical stability of", "stability of individual", "of individual cells", "individual cells and", "cells and epithelial", "and epithelial tissues", "tissues moll", "moll et al.", "et al. 2008", "al. 2008 .", "keratins are the major", "are the major structural", "the major structural protein", "major structural protein of", "structural protein of vertebrate", "protein of vertebrate epidermis", "vertebrate epidermis constituting", "epidermis constituting up", "constituting up to 85%", "up to 85% of", "to 85% of a", "85% of a fully", "of a fully differentiated", "a fully differentiated keratinocyte", "differentiated keratinocyte fuchs", "keratinocyte fuchs 1995", "fuchs 1995 . keratins", "1995 . keratins belong", ". keratins belong to", "keratins belong to a", "belong to a superfamily", "to a superfamily of", "a superfamily of intermediate", "superfamily of intermediate filament", "intermediate filament if", "if proteins that", "proteins that form alpha", "that form alpha helical", "form alpha helical coiled", "alpha helical coiled coil", "helical coiled coil dimers", "coil dimers which", "dimers which associate", "which associate laterally and", "associate laterally and end", "laterally and end to", "and end to end", "end to end to", "to end to form", "end to form approximately", "to form approximately 10", "form approximately 10 nm", "approximately 10 nm diameter", "10 nm diameter filaments.", "nm diameter filaments. keratin", "diameter filaments. keratin filaments", "filaments. keratin filaments are", "keratin filaments are heteropolymeric", "are heteropolymeric formed", "heteropolymeric formed from", "formed from equal amounts", "from equal amounts of", "equal amounts of acidic", "amounts of acidic type", "of acidic type i", "acidic type i and", "type i and basic", "i and basic /neutral", "and basic /neutral type", "basic /neutral type 2", "/neutral type 2 keratins.", "type 2 keratins. humans", "2 keratins. humans have", "keratins. humans have 54", "humans have 54 keratin", "have 54 keratin genes", "keratin genes schweitzer", "genes schweitzer et", "schweitzer et al. 2006", "et al. 2006 .", "al. 2006 . they", "2006 . they have", ". they have highly", "they have highly specific", "have highly specific expression", "highly specific expression patterns", "expression patterns related", "patterns related to", "related to the epithelial", "to the epithelial type", "the epithelial type and", "epithelial type and stage", "type and stage of", "and stage of differentiation.", "stage of differentiation. roughly", "of differentiation. roughly half", "differentiation. roughly half of", "roughly half of human", "half of human keratins", "of human keratins are", "human keratins are specific", "keratins are specific to", "are specific to hair", "specific to hair follicles", "hair follicles langbein", "follicles langbein &", "langbein & schweizer 2005", "& schweizer 2005 .", "schweizer 2005 . keratin", "2005 . keratin filaments", ". keratin filaments bundle", "keratin filaments bundle into", "filaments bundle into tonofilaments", "bundle into tonofilaments that", "into tonofilaments that span", "tonofilaments that span the", "that span the cytoplasm", "span the cytoplasm and", "the cytoplasm and bind", "cytoplasm and bind to", "and bind to desmosomes", "bind to desmosomes and", "to desmosomes and other", "desmosomes and other cell", "and other cell membrane", "other cell membrane structures", "membrane structures waschke", "structures waschke 2008", "waschke 2008 . this", "2008 . this reflects", ". this reflects their", "this reflects their primary", "reflects their primary function", "primary function maintaining", "function maintaining the", "maintaining the mechanical stability", "the mechanical stability of", "mechanical stability of individual", "stability of individual cells", "of individual cells and", "individual cells and epithelial", "cells and epithelial tissues", "epithelial tissues moll", "tissues moll et", "moll et al. 2008", "et al. 2008 .", "keratins are the major structural", "are the major structural protein", "the major structural protein of", "major structural protein of vertebrate", "structural protein of vertebrate epidermis", "of vertebrate epidermis constituting", "vertebrate epidermis constituting up", "epidermis constituting up to", "constituting up to 85% of", "up to 85% of a", "to 85% of a fully", "85% of a fully differentiated", "of a fully differentiated keratinocyte", "fully differentiated keratinocyte fuchs", "differentiated keratinocyte fuchs 1995", "keratinocyte fuchs 1995 .", "fuchs 1995 . keratins belong", "1995 . keratins belong to", ". keratins belong to a", "keratins belong to a superfamily", "belong to a superfamily of", "to a superfamily of intermediate", "a superfamily of intermediate filament", "of intermediate filament if", "filament if proteins", "if proteins that form", "proteins that form alpha helical", "that form alpha helical coiled", "form alpha helical coiled coil", "alpha helical coiled coil dimers", "coiled coil dimers which", "coil dimers which associate", "dimers which associate laterally", "which associate laterally and end", "associate laterally and end to", "laterally and end to end", "and end to end to", "end to end to form", "to end to form approximately", "end to form approximately 10", "to form approximately 10 nm", "form approximately 10 nm diameter", "approximately 10 nm diameter filaments.", "10 nm diameter filaments. keratin", "nm diameter filaments. keratin filaments", "diameter filaments. keratin filaments are", "filaments. keratin filaments are heteropolymeric", "filaments are heteropolymeric formed", "are heteropolymeric formed from", "heteropolymeric formed from equal", "formed from equal amounts of", "from equal amounts of acidic", "equal amounts of acidic type", "amounts of acidic type i", "of acidic type i and", "acidic type i and basic", "type i and basic /neutral", "i and basic /neutral type", "and basic /neutral type 2", "basic /neutral type 2 keratins.", "/neutral type 2 keratins. humans", "type 2 keratins. humans have", "2 keratins. humans have 54", "keratins. humans have 54 keratin", "humans have 54 keratin genes", "54 keratin genes schweitzer", "keratin genes schweitzer et", "genes schweitzer et al.", "schweitzer et al. 2006 .", "et al. 2006 . they", "al. 2006 . they have", "2006 . they have highly", ". they have highly specific", "they have highly specific expression", "have highly specific expression patterns", "specific expression patterns related", "expression patterns related to", "patterns related to the", "related to the epithelial type", "to the epithelial type and", "the epithelial type and stage", "epithelial type and stage of", "type and stage of differentiation.", "and stage of differentiation. roughly", "stage of differentiation. roughly half", "of differentiation. roughly half of", "differentiation. roughly half of human", "roughly half of human keratins", "half of human keratins are", "of human keratins are specific", "human keratins are specific to", "keratins are specific to hair", "are specific to hair follicles", "to hair follicles langbein", "hair follicles langbein &", "follicles langbein & schweizer", "langbein & schweizer 2005 .", "& schweizer 2005 . keratin", "schweizer 2005 . keratin filaments", "2005 . keratin filaments bundle", ". keratin filaments bundle into", "keratin filaments bundle into tonofilaments", "filaments bundle into tonofilaments that", "bundle into tonofilaments that span", "into tonofilaments that span the", "tonofilaments that span the cytoplasm", "that span the cytoplasm and", "span the cytoplasm and bind", "the cytoplasm and bind to", "cytoplasm and bind to desmosomes", "and bind to desmosomes and", "bind to desmosomes and other", "to desmosomes and other cell", "desmosomes and other cell membrane", "and other cell membrane structures", "cell membrane structures waschke", "membrane structures waschke 2008", "structures waschke 2008 .", "waschke 2008 . this reflects", "2008 . this reflects their", ". this reflects their primary", "this reflects their primary function", "their primary function maintaining", "primary function maintaining the", "function maintaining the mechanical", "maintaining the mechanical stability of", "the mechanical stability of individual", "mechanical stability of individual cells", "stability of individual cells and", "of individual cells and epithelial", "individual cells and epithelial tissues", "and epithelial tissues moll", "epithelial tissues moll et", "tissues moll et al.", "moll et al. 2008 ." ] }, { "record_id": "GLY_000594_1_535", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6807004", "r hsa", "hsa 6807004", "r hsa 6807004" ] }, { "record_id": "GLY_000594_1_535", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of met", "met activity", "negative regulation of", "regulation of met", "of met activity", "negative regulation of met", "regulation of met activity", "negative regulation of met activity", "signaling by", "by met", "met receptor", "receptor is", "is negatively", "negatively regulated", "regulated mainly", "mainly by", "receptor dephosphorylation", "dephosphorylation or", "or met", "receptor degradation.", "degradation. protein", "protein tyrosine", "tyrosine phosphatase", "phosphatase ptprj", "ptprj dephosphorylates", "dephosphorylates met", "met tyrosine", "tyrosine residue", "residue y1349", "thus removing", "removing the", "the docking", "docking site", "site for", "for the", "the gab1", "gab1 adapter", "palka et", "et al.", "al. 2003", "2003 .", ". protein", "tyrosine phosphatases", "phosphatases ptpn1", "ptpn1 and", "and ptpn2", "ptpn2 dephosphorylate", "dephosphorylate met", "met tyrosines", "tyrosines y1234", "y1234 and", "and y1235", "y1235 in", "in the", "the kinase", "kinase activation", "activation loop", "thus attenuating", "attenuating catalytic", "catalytic activity", "activity of", "sangwan et", "al. 2008", "2008 .", ". the", "the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase cbl", "cbl promotes", "promotes ubiquitination", "ubiquitination of", "of the", "the activated", "activated met", "receptor and", "and subsequent", "subsequent met", "met degradation.", "degradation. cbl", "cbl 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2002", "2002 .", ". lrig1", "lrig1 promotes", "promotes lysosome", "lysosome dependent", "dependent degradation", "degradation of", "met in", "the absence", "absence of", "of hgf", "hgf mediated", "mediated activation", "lee et", "al. 2014", "oh et", "2014 .
met", ".
met mediated", "activation of", "of ras", "ras signaling", "signaling is", "is inhibited", "inhibited by", "receptor binding", "binding to", "to muc20", "higuchi et", "al. 2004", "or ranbp10", "wang et", "2004 .", "signaling by met", "by met receptor", "met receptor is", "receptor is negatively", "is negatively regulated", "negatively regulated mainly", "regulated mainly by", "mainly by met", "met receptor dephosphorylation", "receptor dephosphorylation or", "dephosphorylation or met", "or met receptor", "met receptor degradation.", "receptor degradation. protein", "degradation. protein tyrosine", "protein tyrosine phosphatase", "tyrosine phosphatase ptprj", "phosphatase ptprj dephosphorylates", "ptprj dephosphorylates met", "dephosphorylates met tyrosine", "met tyrosine residue", "tyrosine residue y1349", "y1349 thus", "thus removing the", "removing the docking", "the docking site", "docking site for", "site for the", "for the gab1", "the gab1 adapter", "adapter palka", "palka et al.", "et al. 2003", "al. 2003 .", "2003 . protein", ". protein tyrosine", "protein tyrosine phosphatases", "tyrosine phosphatases ptpn1", "phosphatases ptpn1 and", "ptpn1 and ptpn2", "and ptpn2 dephosphorylate", "ptpn2 dephosphorylate met", "dephosphorylate met tyrosines", "met tyrosines y1234", "tyrosines y1234 and", "y1234 and y1235", "and y1235 in", "y1235 in the", "in the kinase", "the kinase activation", "kinase activation loop", "loop thus", "thus attenuating catalytic", "attenuating catalytic activity", "catalytic activity of", "activity of met", "met sangwan", "sangwan et al.", "et al. 2008", "al. 2008 .", "2008 . the", ". the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase cbl", "ligase cbl promotes", "cbl promotes ubiquitination", "promotes ubiquitination of", "ubiquitination of the", "of the activated", "the activated met", "activated met receptor", "met receptor and", "receptor and subsequent", "and subsequent met", "subsequent met degradation.", "met degradation. cbl", "degradation. cbl contains", "cbl contains a", "contains a ring", "a ring finger", "ring finger domain", "finger domain that", "domain that engages", "that engages e2", "engages e2 protein", "e2 protein ubiquitin", "protein ubiquitin ligases", "ubiquitin ligases to", "ligases to mediate", "to mediate ubiquitination", "mediate ubiquitination of", "ubiquitination of met", "met which", "which may occur", "may occur at", "occur at the", "at the cell", "the cell membrane", "cell membrane or", "membrane or in", "or in the", "in the early", "the early endocytic", "early endocytic compartment.", "endocytic compartment. ubiquitinated", "compartment. ubiquitinated met", "ubiquitinated met is", "met is degraded", "is degraded in", "degraded in a", "in a late", "a late endosomal", "late endosomal or", "endosomal or lysosomal", "or lysosomal compartment", "lysosomal compartment in", "compartment in a", "in a proteasome", "a proteasome dependent", "proteasome dependent manner.", "dependent manner. the", "manner. the involvement", "the involvement of", "involvement of proteasome", "of proteasome in", "proteasome in met", "in met degradation", "met degradation seems", "degradation seems to", "seems to be", "to be indirect", "indirect through", "through an effect", "an effect on", "effect on met", "on met endocytic", "met endocytic trafficking", "trafficking jeffers", "jeffers et al.", "et al. 1997", "1997 peschard", "peschard et al.", "et al. 2001", "2001 hammond", "hammond et al.", "2001 petrelli", "petrelli et al.", "et al. 2002", "al. 2002 .", "2002 . lrig1", ". lrig1 promotes", "lrig1 promotes lysosome", "promotes lysosome dependent", "lysosome dependent degradation", "dependent degradation of", "degradation of met", "of met in", "met in the", "in the absence", "the absence of", "absence of hgf", "of hgf mediated", "hgf mediated activation", "activation lee", "lee et al.", "et al. 2014", "2014 oh", "oh et al.", "al. 2014 .
met", "2014 .
met mediated", ".
met mediated activation", "mediated activation of", "activation of ras", "of ras signaling", "ras signaling is", "signaling is inhibited", "is inhibited by", "inhibited by met", "met receptor binding", "receptor binding to", "binding to muc20", "muc20 higuchi", "higuchi et al.", "et al. 2004", "2004 or", "ranbp10 wang", "wang et al.", "al. 2004 .", "signaling by met receptor", "by met receptor is", "met receptor is negatively", "receptor is negatively regulated", "is negatively regulated mainly", "negatively regulated mainly by", "regulated mainly by met", "mainly by met receptor", "by met receptor dephosphorylation", "met receptor dephosphorylation or", "receptor dephosphorylation or met", "dephosphorylation or met receptor", "or met receptor degradation.", "met receptor degradation. protein", "receptor degradation. protein tyrosine", "degradation. protein tyrosine phosphatase", "protein tyrosine phosphatase ptprj", "tyrosine phosphatase ptprj dephosphorylates", "phosphatase ptprj dephosphorylates met", "ptprj dephosphorylates met tyrosine", "dephosphorylates met tyrosine residue", "met tyrosine residue y1349", "residue y1349 thus", "y1349 thus removing", "thus removing the docking", "removing the docking site", "the docking site for", "docking site for the", "site for the gab1", "for the gab1 adapter", "gab1 adapter palka", "adapter palka et", "palka et al. 2003", "et al. 2003 .", "al. 2003 . protein", "2003 . protein tyrosine", ". protein tyrosine phosphatases", "protein tyrosine phosphatases ptpn1", "tyrosine phosphatases ptpn1 and", "phosphatases ptpn1 and ptpn2", "ptpn1 and ptpn2 dephosphorylate", "and ptpn2 dephosphorylate met", "ptpn2 dephosphorylate met tyrosines", "dephosphorylate met tyrosines y1234", "met tyrosines y1234 and", "tyrosines y1234 and y1235", "y1234 and y1235 in", "and y1235 in the", "y1235 in the kinase", "in the kinase activation", "the kinase activation loop", "activation loop thus", "loop thus attenuating", "thus attenuating catalytic activity", "attenuating catalytic activity of", "catalytic activity of met", "of met sangwan", "met sangwan et", "sangwan et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the e3", ". the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase cbl", "ubiquitin ligase cbl promotes", "ligase cbl promotes ubiquitination", "cbl promotes ubiquitination of", "promotes ubiquitination of the", "ubiquitination of the activated", "of the activated met", "the activated met receptor", "activated met receptor and", "met receptor and subsequent", "receptor and subsequent met", "and subsequent met degradation.", "subsequent met degradation. cbl", "met degradation. cbl contains", "degradation. cbl contains a", "cbl contains a ring", "contains a ring finger", "a ring finger domain", "ring finger domain that", "finger domain that engages", "domain that engages e2", "that engages e2 protein", "engages e2 protein ubiquitin", "e2 protein ubiquitin ligases", "protein ubiquitin ligases to", "ubiquitin ligases to mediate", "ligases to mediate ubiquitination", "to mediate ubiquitination of", "mediate ubiquitination of met", "of met which", "met which may", "which may occur at", "may occur at the", "occur at the cell", "at the cell membrane", "the cell membrane or", "cell membrane or in", "membrane or in the", "or in the early", "in the early endocytic", "the early endocytic compartment.", "early endocytic compartment. ubiquitinated", "endocytic compartment. ubiquitinated met", "compartment. ubiquitinated met is", "ubiquitinated met is degraded", "met is degraded in", "is degraded in a", "degraded in a late", "in a late endosomal", "a late endosomal or", "late endosomal or lysosomal", "endosomal or lysosomal compartment", "or lysosomal compartment in", "lysosomal compartment in a", "compartment in a proteasome", "in a proteasome dependent", "a proteasome dependent manner.", "proteasome dependent manner. the", "dependent manner. the involvement", "manner. the involvement of", "the involvement of proteasome", "involvement of proteasome in", "of proteasome in met", "proteasome in met degradation", "in met degradation seems", "met degradation seems to", "degradation seems to be", "seems to be indirect", "be indirect through", "indirect through an", "through an effect on", "an effect on met", "effect on met endocytic", "on met endocytic trafficking", "endocytic trafficking jeffers", "trafficking jeffers et", "jeffers et al. 1997", "al. 1997 peschard", "1997 peschard et", "peschard et al. 2001", "al. 2001 hammond", "2001 hammond et", "hammond et al. 2001", "al. 2001 petrelli", "2001 petrelli et", "petrelli et al. 2002", "et al. 2002 .", "al. 2002 . lrig1", "2002 . lrig1 promotes", ". lrig1 promotes lysosome", "lrig1 promotes lysosome dependent", "promotes lysosome dependent degradation", "lysosome dependent degradation of", "dependent degradation of met", "degradation of met in", "of met in the", "met in the absence", "in the absence of", "the absence of hgf", "absence of hgf mediated", "of hgf mediated activation", "mediated activation lee", "activation lee et", "lee et al. 2014", "al. 2014 oh", "2014 oh et", "oh et al. 2014", "et al. 2014 .
met", "al. 2014 .
met mediated", "2014 .
met mediated activation", ".
met mediated activation of", "mediated activation of ras", "activation of ras signaling", "of ras signaling is", "ras signaling is inhibited", "signaling is inhibited by", "is inhibited by met", "inhibited by met receptor", "by met receptor binding", "met receptor binding to", "receptor binding to muc20", "to muc20 higuchi", "muc20 higuchi et", "higuchi et al. 2004", "al. 2004 or", "2004 or ranbp10", "or ranbp10 wang", "ranbp10 wang et", "wang et al. 2004", "et al. 2004 .", "signaling by met receptor is", "by met receptor is negatively", "met receptor is negatively regulated", "receptor is negatively regulated mainly", "is negatively regulated mainly by", "negatively regulated mainly by met", "regulated mainly by met receptor", "mainly by met receptor dephosphorylation", "by met receptor dephosphorylation or", "met receptor dephosphorylation or met", "receptor dephosphorylation or met receptor", "dephosphorylation or met receptor degradation.", "or met receptor degradation. protein", "met receptor degradation. protein tyrosine", "receptor degradation. protein tyrosine phosphatase", "degradation. protein tyrosine phosphatase ptprj", "protein tyrosine phosphatase ptprj dephosphorylates", "tyrosine phosphatase ptprj dephosphorylates met", "phosphatase ptprj dephosphorylates met tyrosine", "ptprj dephosphorylates met tyrosine residue", "dephosphorylates met tyrosine residue y1349", "tyrosine residue y1349 thus", "residue y1349 thus removing", "y1349 thus removing the", "thus removing the docking site", "removing the docking site for", "the docking site for the", "docking site for the gab1", "site for the gab1 adapter", "the gab1 adapter palka", "gab1 adapter palka et", "adapter palka et al.", "palka et al. 2003 .", "et al. 2003 . protein", "al. 2003 . protein tyrosine", "2003 . protein tyrosine phosphatases", ". protein tyrosine phosphatases ptpn1", "protein tyrosine phosphatases ptpn1 and", "tyrosine phosphatases ptpn1 and ptpn2", "phosphatases ptpn1 and ptpn2 dephosphorylate", "ptpn1 and ptpn2 dephosphorylate met", "and ptpn2 dephosphorylate met tyrosines", "ptpn2 dephosphorylate met tyrosines y1234", "dephosphorylate met tyrosines y1234 and", "met tyrosines y1234 and y1235", "tyrosines y1234 and y1235 in", "y1234 and y1235 in the", "and y1235 in the kinase", "y1235 in the kinase activation", "in the kinase activation loop", "kinase activation loop thus", "activation loop thus attenuating", "loop thus attenuating catalytic", "thus attenuating catalytic activity of", "attenuating catalytic activity of met", "activity of met sangwan", "of met sangwan et", "met sangwan et al.", "sangwan et al. 2008 .", "et al. 2008 . the", "al. 2008 . the e3", "2008 . the e3 ubiquitin", ". the e3 ubiquitin ligase", "the e3 ubiquitin ligase cbl", "e3 ubiquitin ligase cbl promotes", "ubiquitin ligase cbl promotes ubiquitination", "ligase cbl promotes ubiquitination of", "cbl promotes ubiquitination of the", "promotes ubiquitination of the activated", "ubiquitination of the activated met", "of the activated met receptor", "the activated met receptor and", "activated met receptor and subsequent", "met receptor and subsequent met", "receptor and subsequent met degradation.", "and subsequent met degradation. cbl", "subsequent met degradation. cbl contains", "met degradation. cbl contains a", "degradation. cbl contains a ring", "cbl contains a ring finger", "contains a ring finger domain", "a ring finger domain that", "ring finger domain that engages", "finger domain that engages e2", "domain that engages e2 protein", "that engages e2 protein ubiquitin", "engages e2 protein ubiquitin ligases", "e2 protein ubiquitin ligases to", "protein ubiquitin ligases to mediate", "ubiquitin ligases to mediate ubiquitination", "ligases to mediate ubiquitination of", "to mediate ubiquitination of met", "ubiquitination of met which", "of met which may", "met which may occur", "which may occur at the", "may occur at the cell", "occur at the cell membrane", "at the cell membrane or", "the cell membrane or in", "cell membrane or in the", "membrane or in the early", "or in the early endocytic", "in the early endocytic compartment.", "the early endocytic compartment. ubiquitinated", "early endocytic compartment. ubiquitinated met", "endocytic compartment. ubiquitinated met is", "compartment. ubiquitinated met is degraded", "ubiquitinated met is degraded in", "met is degraded in a", "is degraded in a late", "degraded in a late endosomal", "in a late endosomal or", "a late endosomal or lysosomal", "late endosomal or lysosomal compartment", "endosomal or lysosomal compartment in", "or lysosomal compartment in a", "lysosomal compartment in a proteasome", "compartment in a proteasome dependent", "in a proteasome dependent manner.", "a proteasome dependent manner. the", "proteasome dependent manner. the involvement", "dependent manner. the involvement of", "manner. the involvement of proteasome", "the involvement of proteasome in", "involvement of proteasome in met", "of proteasome in met degradation", "proteasome in met degradation seems", "in met degradation seems to", "met degradation seems to be", "degradation seems to be indirect", "to be indirect through", "be indirect through an", "indirect through an effect", "through an effect on met", "an effect on met endocytic", "effect on met endocytic trafficking", "met endocytic trafficking jeffers", "endocytic trafficking jeffers et", "trafficking jeffers et al.", "et al. 1997 peschard", "al. 1997 peschard et", "1997 peschard et al.", "et al. 2001 hammond", "al. 2001 hammond et", "2001 hammond et al.", "et al. 2001 petrelli", "al. 2001 petrelli et", "2001 petrelli et al.", "petrelli et al. 2002 .", "et al. 2002 . lrig1", "al. 2002 . lrig1 promotes", "2002 . lrig1 promotes lysosome", ". lrig1 promotes lysosome dependent", "lrig1 promotes lysosome dependent degradation", "promotes lysosome dependent degradation of", "lysosome dependent degradation of met", "dependent degradation of met in", "degradation of met in the", "of met in the absence", "met in the absence of", "in the absence of hgf", "the absence of hgf mediated", "absence of hgf mediated activation", "hgf mediated activation lee", "mediated activation lee et", "activation lee et al.", "et al. 2014 oh", "al. 2014 oh et", "2014 oh et al.", "oh et al. 2014 .
met", "et al. 2014 .
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met mediated activation of", ".
met mediated activation of ras", "mediated activation of ras signaling", "activation of ras signaling is", "of ras signaling is inhibited", "ras signaling is inhibited by", "signaling is inhibited by met", "is inhibited by met receptor", "inhibited by met receptor binding", "by met receptor binding to", "met receptor binding to muc20", "binding to muc20 higuchi", "to muc20 higuchi et", "muc20 higuchi et al.", "et al. 2004 or", "al. 2004 or ranbp10", "or ranbp10 wang et", "ranbp10 wang et al.", "wang et al. 2004 ." ] }, { "record_id": "GLY_000594_1_536", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6807505", "r hsa", "hsa 6807505", "r hsa 6807505" ] }, { "record_id": "GLY_000594_1_536", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase ii", "ii transcribes", "transcribes snrna", "snrna genes", "rna polymerase ii", "polymerase ii transcribes", "ii transcribes snrna", "transcribes snrna genes", "rna polymerase ii transcribes", "polymerase ii transcribes snrna", "ii transcribes snrna genes", "rna polymerase ii transcribes snrna", "polymerase ii transcribes snrna genes", "small nuclear", "nuclear rnas", "play key", "key roles", "roles in", "in splicing", "splicing and", "and some", "some of", "of them", "specifically the", "the u1", "u1 and", "and u2", "u2 snrnas", "are encoded", "encoded by", "by multicopy", "multicopy snrna", "snrna gene", "gene clusters", "clusters containing", "containing tandem", "tandem arrays", "arrays of", "of genes", "about 30", "30 in", "in the", "the rnu1", "rnu1 cluster", "bernstein et", "et al.", "al. 1985", "and about", "about 10", "10 20", "20 in", "the rnu2", "rnu2 cluster", "van ardsell", "ardsell and", "and weiner", "weiner 1984", "1984 .", ". whereas", "whereas u6", "u6 snrna", "genes are", "are transcribed", "transcribed by", "by rna", "polymerase iii", "u1 u2", "and u12", "u12 genes", "polymerase ii.", "ii. transcription", "transcription of", "of the", "u2 genes", "genes has", "has been", "been most", "most extensively", "extensively studied", "studied and", "and the", "the other", "other snrna", "genes as", "as well", "well as", "as other", "other genes", "genes with", "with similar", "similar promoter", "promoter structures", "for example", "example the", "the snord13", "snord13 gene", "are inferred", "inferred to", "to be", "be transcribed", "by similar", "similar reactions.", "reactions. the", "the snrna", "genes transcribed", "ii are", "are distinguished", "distinguished from", "from mrna", "mrna encoding", "encoding genes", "genes by", "by the", "the presence", "presence of", "of a", "a proximal", "proximal sequence", "sequence element", "rather than", "than a", "a tata", "tata box", "box and", "the integrator", "integrator complex", "complex rather", "than the", "the mediator", "mediator complex", "reviewed in", "in egloff", "egloff et", "al. 2008", "jawdeker and", "and henry", "henry 2008", "2008 .
the", ".
the snrna", "are among", "among the", "the most", "most rapidly", "rapidly transcribed", "transcribed genes", "genes in", "the genome.", "genome. the", "the 5'", "5' transcribed", "transcribed region", "region of", "the u2", "u2 snrna", "gene is", "is largely", "largely single", "single stranded", "stranded during", "during interphase", "interphase and", "and metaphase", "pavelitz et", "and chromatin", "chromatin within", "within the", "the transcribed", "region is", "is cleared", "cleared of", "of nucleosomes", "o'reilly et", "al. 2014", "2014 .", ". transcriptional", "transcriptional activation", "activation of", "the rna", "ii transcribed", "transcribed snrna", "genes begins", "begins with", "with binding", "binding of", "of transcription", "transcription factors", "factors to", "to the", "the distal", "distal sequence", "the promoter", "in hernandez", "hernandez 2001", "2008 .", ". the", "the factors", "which include", "include pou2f1", "oct 1", "oct 2", "and sp1", "promote binding", "the snapc", "snapc complex", "also known", "known as", "as ptf", "ptf and", "and pbp", "the pse.", "pse. snapc", "snapc helps", "helps clear", "clear the", "the gene", "gene of", "and recruits", "recruits initiation", "initiation factors", "and sntafc:tbp", "which recruit", "recruit rna", "ii. phosphorylation", "phosphorylation of", "the c", "c terminal", "terminal domain", "of rna", "egloff and", "and murphy", "murphy 2008", "by cdk7", "cdk7 recruits", "recruits rpap2", "rpap2 and", "which is", "is required", "required for", "for later", "later processing", "processing of", "the 3'", "3' end", "end of", "the pre", "pre snrna", "snrna transcript", "in chen", "chen and", "and wagner", "wagner 2010", "baillat and", "wagner 2015", "2015 .", "the little", "little elongation", "elongation complex", "also appears", "appears to", "to bind", "bind around", "around the", "the time", "time of", "transcription initiation", "hu et", "al. 2013", "2013 .", ". as", "as transcription", "transcription proceeds", "rpap2 dephosphorylates", "dephosphorylates serine", "serine 5", "5 and", "and p", "p tefb", "tefb phosphorylates", "phosphorylates serine", "serine 2", "2 of", "the ctd.", "ctd. as", "transcription reaches", "reaches the", "the end", "gene serine", "serine 7", "7 of", "the ctd", "ctd is", "is phosphorylated.", "phosphorylated. these", "these marks", "marks serve", "serve to", "bind protein", "protein complexes", "complexes and", "and are", "are required", "for 3'", "3' processing", ". after", "after transcription", "proceeds through", "through the", "the conserved", "conserved 3'", "processing sequence", "sequence of", "snrna the", "complex cleaves", "cleaves the", "pre snrna.", "snrna. transcription", "transcription then", "then terminates", "terminates downstream", "downstream in", "in a", "a less", "less well", "well characterized", "characterized reaction", "reaction that", "that requires", "requires elements", "elements of", "the polyadenylation", "polyadenylation system.", "small nuclear rnas", "rnas snrnas", "snrnas play", "play key roles", "key roles in", "roles in splicing", "in splicing and", "splicing and some", "and some of", "some of them", "them specifically", "specifically the u1", "the u1 and", "u1 and u2", "and u2 snrnas", "snrnas are", "are encoded by", "encoded by multicopy", "by multicopy snrna", "multicopy snrna gene", "snrna gene clusters", "gene clusters containing", "clusters containing tandem", "containing tandem arrays", "tandem arrays of", "arrays of genes", "genes about", "about 30 in", "30 in the", "in the rnu1", "the rnu1 cluster", "cluster bernstein", "bernstein et al.", "et al. 1985", "1985 and", "and about 10", "about 10 20", "10 20 in", "20 in the", "in the rnu2", "the rnu2 cluster", "cluster van", "van ardsell and", "ardsell and weiner", "and weiner 1984", "weiner 1984 .", "1984 . whereas", ". whereas u6", "whereas u6 snrna", "u6 snrna genes", "snrna genes are", "genes are transcribed", "are transcribed by", "transcribed by rna", "by rna polymerase", "rna polymerase iii", "iii u1", "u2 u4", "u4 u4atac", "u4atac u5", "u5 u11", "u11 and", "and u12 genes", "u12 genes are", "rna polymerase ii.", "polymerase ii. transcription", "ii. transcription of", "transcription of the", "of the u1", "and u2 genes", "u2 genes has", "genes has been", "has been most", "been most extensively", "most extensively studied", "extensively studied and", "studied and the", "and the other", "the other snrna", "other snrna genes", "snrna genes as", "genes as well", "as well as", "well as other", "as other genes", "other genes with", "genes with similar", "with similar promoter", "similar promoter structures", "structures for", "for example the", "example the snord13", "the snord13 gene", "gene are", "are inferred to", "inferred to be", "to be transcribed", "be transcribed by", "transcribed by similar", "by similar reactions.", "similar reactions. the", "reactions. the snrna", "the snrna genes", "snrna genes transcribed", "genes transcribed by", "polymerase ii are", "ii are distinguished", "are distinguished from", "distinguished from mrna", "from mrna encoding", "mrna encoding genes", "encoding genes by", "genes by the", "by the presence", "the presence of", "presence of a", "of a proximal", "a proximal sequence", "proximal sequence element", "element pse", "pse rather", "rather than a", "than a tata", "a tata box", "tata box and", "box and the", "and the presence", "presence of the", "of the integrator", "the integrator complex", "integrator complex rather", "complex rather than", "rather than the", "than the mediator", "the mediator complex", "complex reviewed", "reviewed in egloff", "in egloff et", "egloff et al.", "et al. 2008", "2008 jawdeker", "jawdeker and henry", "and henry 2008", "henry 2008 .
the", "2008 .
the snrna", ".
the snrna genes", "genes are among", "are among the", "among the most", "the most rapidly", "most rapidly transcribed", "rapidly transcribed genes", "transcribed genes in", "genes in the", "in the genome.", "the genome. the", "genome. the 5'", "the 5' transcribed", "5' transcribed region", "transcribed region of", "region of the", "of the u2", "the u2 snrna", "u2 snrna gene", "snrna gene is", "gene is largely", "is largely single", "largely single stranded", "single stranded during", "stranded during interphase", "during interphase and", "interphase and metaphase", "metaphase pavelitz", "pavelitz et al.", "2008 and", "and chromatin within", "chromatin within the", "within the transcribed", "the transcribed region", "transcribed region is", "region is cleared", "is cleared of", "cleared of nucleosomes", "nucleosomes o'reilly", "o'reilly et al.", "et al. 2014", "al. 2014 .", "2014 . transcriptional", ". transcriptional activation", "transcriptional activation of", "activation of the", 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layer", "layer that", "that confers", "confers rigidity", "rigidity to", "to the", "allows keratin", "keratin filaments", "filaments to", "to attach", "attach to", "to any", "any location", "location in", "the cell", "cell membrane", "kirfel et", "al. 2003", "and acts", "acts as", "as a", "a water", "water impermeable", "impermeable barrier.", "barrier. the", "ce has", "has two", "two functional", "functional parts:", "parts: covalently", "covalently cross", "cross linked", "linked proteins", "10 nm", "nm thick", "that comprise", "comprise the", "the backbone", "backbone of", "the envelope", "envelope and", "and covalently", "covalently linked", "linked lipids", "5 nm", "that coat", "coat the", "the exterior", "eckert et", "al. 2005", "2005 .", ". desmosomal", "desmosomal components", "components are", "are crosslinked", "crosslinked to", "ce to", "to form", "form corneodesmosomes", "which bind", "bind cornified", "cornified cells", "cells together", "ishida yamamoto", "yamamoto et", "al. 2011", "2011 .", ". mature", "mature terminally", "terminally differentiated", "differentiated cornified", "cells consist", "consist mostly", "mostly of", "of keratin", "filaments covalently", "covalently attached", "attached to", "ce embedded", "embedded in", "in lipid", "lipid lamellae", "kalinin et", "al. 2002", "2002 .", ". the", "the exact", "exact composition", "composition of", "envelope varies", "varies between", "between epithelia", "steinert et", "al. 1998", "the relative", "relative amino", "amino acid", "acid composition", "the proteins", "proteins used", "used may", "may determine", "determine differential", "differential mechanical", "mechanical properties", "kartasova et", "al. 1996", "1996 .", "as keratinocytes progress", "keratinocytes progress towards", "progress towards the", "towards the upper", "the upper epidermis", "epidermis they", "they undergo a", "undergo a unique", "a unique process", "unique process of", "process of cell", "of cell death", "cell death termed", "death termed cornification", "cornification eckhart", "eckhart et al.", "et al. 2013", "al. 2013 .", "2013 . this", ". this involves", "this involves the", "involves the crosslinking", "the crosslinking of", "crosslinking of keratinocyte", "of keratinocyte proteins", "keratinocyte proteins such", "proteins such as", "such as loricrin", "as loricrin and", "loricrin and involucrin", "and involucrin by", "involucrin by transglutaminases", "by transglutaminases and", "transglutaminases and the", "and the breakdown", "the breakdown of", "breakdown of the", "of the nucleus", "the nucleus and", "nucleus and other", "and other organelles", "other organelles by", "organelles by intracellular", "by intracellular and", "intracellular and secreted", "and secreted proteases", "proteases eckhart", "et al. 2000", "2000 denecker", "denecker et al.", "et al. 2008", "al. 2008 .", "2008 . this", ". this process", "this process is", "process is strictly", "is strictly regulated", "strictly regulated by", "regulated by the", "by the ca2+", "the ca2+ concentration", "ca2+ concentration gradient", "concentration gradient in", "gradient in the", "in the epidermis", "epidermis esholtz", "esholtz et al.", "et al. 2014", "al. 2014 .", "2014 . loricrin", ". loricrin and", "and involucrin are", "involucrin are encoded", "are encoded in", "encoded in \u2018epidermal", "in \u2018epidermal differentiation", "\u2018epidermal differentiation complex\u2019", "differentiation complex\u2019 linked", "complex\u2019 linked to", "linked to a", "to a large", "a large number", "large number of", "number of genes", "of genes encoding", "genes encoding nonredundant", "encoding nonredundant components", "nonredundant components of", "components of the", "of the ce", "ce kypriotou", "kypriotou et al.", "et al. 2012", "2012 niehues", "niehues et al.", "et al. 2016", "al. 2016 .", "2016 . keratinocytes", ". keratinocytes produce", "keratinocytes produce specialized", "produce specialized proteins", "specialized proteins and", "proteins and lipids", "and lipids which", "lipids which are", "which are used", "are used to", "used to construct", "to construct the", "construct the cornified", "envelope ce", "a heavily crosslinked", "heavily crosslinked submembranous", "crosslinked submembranous layer", "submembranous layer that", "layer that confers", "that confers rigidity", "confers rigidity to", "rigidity to the", "to the upper", "epidermis allows", "allows keratin filaments", "keratin filaments to", "filaments to attach", "to attach to", "attach to any", "to any location", "any location in", "location in the", "in the cell", "the cell membrane", "membrane kirfel", "kirfel et al.", "et al. 2003", "2003 and", "and acts as", "acts as a", "as a water", "a water impermeable", "water impermeable barrier.", "impermeable barrier. the", "barrier. the ce", "the ce has", "ce has two", "has two functional", "two functional parts:", "functional parts: covalently", "parts: covalently cross", "covalently cross linked", "cross linked proteins", "proteins 10", "10 nm thick", "thick that", "that comprise the", "comprise the backbone", "the backbone of", "backbone of the", "of the envelope", "the envelope and", "envelope and covalently", "and covalently linked", "covalently linked lipids", "lipids 5", "5 nm thick", "that coat the", "coat the exterior", "exterior eckert", "eckert et al.", "et al. 2005", "al. 2005 .", "2005 . desmosomal", ". desmosomal components", "desmosomal components are", "components are crosslinked", "are crosslinked to", "crosslinked to the", "to the ce", "the ce to", "ce to form", "to form corneodesmosomes", "corneodesmosomes which", "which bind cornified", "bind cornified cells", "cornified cells together", "together ishida", "ishida yamamoto et", "yamamoto et al.", "et al. 2011", "al. 2011 .", "2011 . mature", ". mature terminally", "mature terminally differentiated", "terminally differentiated cornified", "differentiated cornified cells", "cornified cells consist", "cells consist mostly", "consist mostly of", "mostly of keratin", "of keratin filaments", "keratin filaments covalently", "filaments covalently attached", "covalently attached to", "attached to the", "the ce embedded", "ce embedded in", "embedded in lipid", "in lipid lamellae", "lamellae kalinin", "kalinin et al.", "et al. 2002", "al. 2002 .", "2002 . the", ". the exact", "the exact composition", "exact composition of", "composition of the", "cornified envelope varies", "envelope varies between", "varies between epithelia", "epithelia steinert", "steinert et al.", "et al. 1998", "the relative amino", "relative amino acid", "amino acid composition", "acid composition of", "of the proteins", "the proteins used", "proteins used may", "used may determine", "may determine differential", "determine differential mechanical", "differential mechanical properties", "properties kartasova", "kartasova et al.", "et al. 1996", "al. 1996 .", "as keratinocytes progress towards", "keratinocytes progress towards the", "progress towards the upper", "towards the upper epidermis", "upper epidermis they", "epidermis they undergo", "they undergo a unique", "undergo a unique process", "a unique process of", "unique process of cell", "process of cell death", "of cell death termed", "cell death termed cornification", "termed cornification eckhart", "cornification eckhart et", "eckhart et al. 2013", "et al. 2013 .", "al. 2013 . this", "2013 . this involves", ". this involves the", "this involves the crosslinking", "involves the crosslinking of", "the crosslinking of keratinocyte", "crosslinking of keratinocyte proteins", "of keratinocyte proteins such", "keratinocyte proteins such as", "proteins such as loricrin", "such as loricrin and", "as loricrin and involucrin", "loricrin and involucrin by", "and involucrin by transglutaminases", "involucrin by transglutaminases and", "by transglutaminases and the", "transglutaminases and the breakdown", "and the breakdown of", "the breakdown of the", "breakdown of the nucleus", "of the nucleus and", "the nucleus and other", "nucleus and other organelles", "and other organelles by", "other organelles by intracellular", "organelles by intracellular and", "by intracellular and secreted", "intracellular and secreted proteases", "secreted proteases eckhart", "proteases eckhart et", "eckhart et al. 2000", "al. 2000 denecker", "2000 denecker et", "denecker et al. 2008", "et al. 2008 .", "al. 2008 . this", "2008 . this process", ". this process is", "this process is strictly", "process is strictly regulated", "is strictly regulated by", "strictly regulated by the", "regulated by the ca2+", "by the ca2+ concentration", "the ca2+ concentration gradient", "ca2+ concentration gradient in", "concentration gradient in the", "gradient in the epidermis", "the epidermis esholtz", "epidermis esholtz et", "esholtz et al. 2014", "et al. 2014 .", "al. 2014 . loricrin", "2014 . loricrin and", ". loricrin and involucrin", "loricrin and involucrin are", "and involucrin are encoded", "involucrin are encoded in", "are encoded in \u2018epidermal", "encoded in \u2018epidermal differentiation", "in \u2018epidermal differentiation complex\u2019", "\u2018epidermal differentiation complex\u2019 linked", "differentiation complex\u2019 linked to", "complex\u2019 linked to a", "linked to a large", "to a large number", "a large number of", "large number of genes", "number of genes encoding", "of genes encoding nonredundant", "genes encoding nonredundant components", "encoding nonredundant components of", "nonredundant components of the", "components of the ce", "the ce kypriotou", "ce kypriotou et", "kypriotou et al. 2012", "al. 2012 niehues", "2012 niehues et", "niehues et al. 2016", "et al. 2016 .", "al. 2016 . keratinocytes", "2016 . keratinocytes produce", ". keratinocytes produce specialized", "keratinocytes produce specialized proteins", "produce specialized proteins and", "specialized proteins and lipids", "proteins and lipids which", "and lipids which are", "lipids which are used", "which are used to", "are used to construct", "used to construct the", "to construct the cornified", "construct the cornified envelope", "cornified envelope ce", "ce a", "a heavily crosslinked submembranous", "heavily crosslinked submembranous layer", "crosslinked submembranous layer that", "submembranous layer that confers", "layer that confers rigidity", "that confers rigidity to", "confers rigidity to the", "rigidity to the upper", "to the upper epidermis", "upper epidermis allows", "epidermis allows keratin", "allows keratin filaments to", "keratin filaments to attach", "filaments to attach to", "to attach to any", "attach to any location", "to any location in", "any location in the", "location in the cell", "in the cell membrane", "cell membrane kirfel", "membrane kirfel et", "kirfel et al. 2003", "al. 2003 and", "2003 and acts", "and acts as a", "acts as a water", "as a water impermeable", "a water impermeable barrier.", "water impermeable barrier. the", "impermeable barrier. the ce", "barrier. the ce has", "the ce has two", "ce has two functional", "has two functional parts:", "two functional parts: covalently", "functional parts: covalently cross", "parts: covalently cross linked", "covalently cross linked proteins", "linked proteins 10", "proteins 10 nm", "nm thick that", "thick that comprise", "that comprise the backbone", "comprise the backbone of", "the backbone of the", "backbone of the envelope", "of the envelope and", "the envelope and covalently", "envelope and covalently linked", "and covalently linked lipids", "linked lipids 5", "lipids 5 nm", "thick that coat", "that coat the exterior", "the exterior eckert", "exterior eckert et", "eckert et al. 2005", "et al. 2005 .", "al. 2005 . desmosomal", "2005 . desmosomal components", ". desmosomal components are", "desmosomal components are crosslinked", "components are crosslinked to", "are crosslinked to the", "crosslinked to the ce", "to the ce to", "the ce to form", "ce to form corneodesmosomes", "form corneodesmosomes which", "corneodesmosomes which bind", "which bind cornified cells", "bind cornified cells together", "cells together ishida", "together ishida yamamoto", "ishida yamamoto et al.", "yamamoto et al. 2011", "et al. 2011 .", "al. 2011 . mature", "2011 . mature terminally", ". mature terminally differentiated", "mature terminally differentiated cornified", "terminally differentiated cornified cells", "differentiated cornified cells consist", "cornified cells consist mostly", "cells consist mostly of", "consist mostly of keratin", "mostly of keratin filaments", "of keratin filaments covalently", "keratin filaments covalently attached", "filaments covalently attached to", "covalently attached to the", "attached to the ce", "to the ce embedded", "the ce embedded in", "ce embedded in lipid", "embedded in lipid lamellae", "lipid lamellae kalinin", "lamellae kalinin et", "kalinin et al. 2002", "et al. 2002 .", "al. 2002 . the", "2002 . the exact", ". the exact composition", "the exact composition of", "exact composition of the", "composition of the cornified", "the cornified envelope varies", "cornified envelope varies between", "envelope varies between epithelia", "between epithelia steinert", "epithelia steinert et", "steinert et al. 1998", "1998 the", "the relative amino acid", "relative amino acid composition", "amino acid composition of", "acid composition of the", "composition of the proteins", "of the proteins used", "the proteins used may", "proteins used may determine", "used may determine differential", "may determine differential mechanical", "determine differential mechanical properties", "mechanical properties kartasova", "properties kartasova et", "kartasova et al. 1996", "et al. 1996 .", "as keratinocytes progress towards the", "keratinocytes progress towards the upper", "progress towards the upper epidermis", "the upper epidermis they", "upper epidermis they undergo", "epidermis they undergo a", "they undergo a unique process", "undergo a unique process of", "a unique process of cell", "unique process of cell death", "process of cell death termed", "of cell death termed cornification", "death termed cornification eckhart", "termed cornification eckhart et", "cornification eckhart et al.", "eckhart et al. 2013 .", "et al. 2013 . this", "al. 2013 . this involves", "2013 . this involves the", ". this involves the crosslinking", "this involves the crosslinking of", "involves the crosslinking of keratinocyte", "the crosslinking of keratinocyte proteins", "crosslinking of keratinocyte proteins such", "of keratinocyte proteins such as", "keratinocyte proteins such as loricrin", "proteins such as loricrin and", "such as loricrin and involucrin", "as loricrin and involucrin by", "loricrin and involucrin by transglutaminases", "and involucrin by transglutaminases and", "involucrin by transglutaminases and the", "by transglutaminases and the breakdown", "transglutaminases and the breakdown of", "and the breakdown of the", "the breakdown of the nucleus", "breakdown of the nucleus and", "of the nucleus and other", "the nucleus and other organelles", "nucleus and other organelles by", "and other organelles by intracellular", "other organelles by intracellular and", "organelles by intracellular and secreted", "by intracellular and secreted proteases", "and secreted proteases eckhart", "secreted proteases eckhart et", "proteases eckhart et al.", "et al. 2000 denecker", "al. 2000 denecker et", "2000 denecker et al.", "denecker et al. 2008 .", "et al. 2008 . this", "al. 2008 . this process", "2008 . this process is", ". this process is strictly", "this process is strictly regulated", "process is strictly regulated by", "is strictly regulated by the", "strictly regulated by the ca2+", "regulated by the ca2+ concentration", "by the ca2+ concentration gradient", "the ca2+ concentration gradient in", "ca2+ concentration gradient in the", "concentration gradient in the epidermis", "in the epidermis esholtz", "the epidermis esholtz et", "epidermis esholtz et al.", "esholtz et al. 2014 .", "et al. 2014 . loricrin", "al. 2014 . loricrin and", "2014 . loricrin and involucrin", ". loricrin and involucrin are", "loricrin and involucrin are encoded", "and involucrin are encoded in", "involucrin are encoded in \u2018epidermal", "are encoded in \u2018epidermal differentiation", "encoded in \u2018epidermal differentiation complex\u2019", "in \u2018epidermal differentiation complex\u2019 linked", "\u2018epidermal differentiation complex\u2019 linked to", "differentiation complex\u2019 linked to a", "complex\u2019 linked to a large", "linked to a large number", "to a large number of", "a large number of genes", "large number of genes encoding", "number of genes encoding nonredundant", "of genes encoding nonredundant components", "genes encoding nonredundant components of", "encoding nonredundant components of the", "nonredundant components of the ce", "of the ce kypriotou", "the ce kypriotou et", "ce kypriotou et al.", "et al. 2012 niehues", "al. 2012 niehues et", "2012 niehues et al.", "niehues et al. 2016 .", "et al. 2016 . keratinocytes", "al. 2016 . keratinocytes produce", "2016 . keratinocytes produce specialized", ". keratinocytes produce specialized proteins", "keratinocytes produce specialized proteins and", "produce specialized proteins and lipids", "specialized proteins and lipids which", "proteins and lipids which are", "and lipids which are used", "lipids which are used to", "which are used to construct", "are used to construct the", "used to construct the cornified", "to construct the cornified envelope", "the cornified envelope ce", "ce a heavily", "a heavily crosslinked submembranous layer", "heavily crosslinked submembranous layer that", "crosslinked submembranous layer that confers", "submembranous layer that confers rigidity", "layer that confers rigidity to", "that confers rigidity to the", "confers rigidity to the upper", "rigidity to the upper epidermis", "the upper epidermis allows", "upper epidermis allows keratin", "epidermis allows keratin filaments", "allows keratin filaments to attach", "keratin filaments to attach to", "filaments to attach to any", "to attach to any location", "attach to any location in", "to any location in the", "any location in the cell", "location in the cell membrane", "the cell membrane kirfel", "cell membrane kirfel et", "membrane kirfel et al.", "et al. 2003 and", "al. 2003 and acts", "2003 and acts as", "and acts as a water", "acts as a water impermeable", "as a water impermeable barrier.", "a water impermeable barrier. the", "water impermeable barrier. the ce", "impermeable barrier. the ce has", "barrier. the ce has two", "the ce has two functional", "ce has two functional parts:", "has two functional parts: covalently", "two functional parts: covalently cross", "functional parts: covalently cross linked", "parts: covalently cross linked proteins", "cross linked proteins 10", "linked proteins 10 nm", "proteins 10 nm thick", "10 nm thick that", "nm thick that comprise", "thick that comprise the", "that comprise the backbone of", "comprise the backbone of the", "the backbone of the envelope", "backbone of the envelope and", "of the envelope and covalently", "the envelope and covalently linked", "envelope and covalently linked lipids", "covalently linked lipids 5", "linked lipids 5 nm", "lipids 5 nm thick", "5 nm thick that", "nm thick that coat", "thick that coat the", "coat the exterior eckert", "the exterior eckert et", "exterior eckert et al.", "eckert et al. 2005 .", "et al. 2005 . desmosomal", "al. 2005 . desmosomal components", "2005 . desmosomal components are", ". desmosomal components are crosslinked", "desmosomal components are crosslinked to", "components are crosslinked to the", "are crosslinked to the ce", "crosslinked to the ce to", "to the ce to form", "the ce to form corneodesmosomes", "to form corneodesmosomes which", "form corneodesmosomes which bind", "corneodesmosomes which bind cornified", "which bind cornified cells together", "cornified cells together ishida", "cells together ishida yamamoto", "together ishida yamamoto et", "ishida yamamoto et al. 2011", "yamamoto et al. 2011 .", "et al. 2011 . mature", "al. 2011 . mature terminally", "2011 . mature terminally differentiated", ". mature terminally differentiated cornified", "mature terminally differentiated cornified cells", "terminally differentiated cornified cells consist", "differentiated cornified cells consist mostly", "cornified cells consist mostly of", "cells consist mostly of keratin", "consist mostly of keratin filaments", "mostly of keratin filaments covalently", "of keratin filaments covalently attached", "keratin filaments covalently attached to", "filaments covalently attached to the", "covalently attached to the ce", "attached to the ce embedded", "to the ce embedded in", "the ce embedded in lipid", "ce embedded in lipid lamellae", "in lipid lamellae kalinin", "lipid lamellae kalinin et", "lamellae kalinin et al.", "kalinin et al. 2002 .", "et al. 2002 . the", "al. 2002 . the exact", "2002 . the exact composition", ". the exact composition of", "the exact composition of the", "exact composition of the cornified", "composition of the cornified envelope", "of the cornified envelope varies", "the cornified envelope varies between", "cornified envelope varies between epithelia", "varies between epithelia steinert", "between epithelia steinert et", "epithelia steinert et al.", "al. 1998 the", "1998 the relative", "the relative amino acid composition", "relative amino acid composition of", "amino acid composition of the", "acid composition of the proteins", "composition of the proteins used", "of the proteins used may", "the proteins used may determine", "proteins used may determine differential", "used may determine differential mechanical", "may determine differential mechanical 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pip3 is", "2007 . pip3 is necessary", ". pip3 is necessary for", "pip3 is necessary for the", "is necessary for the activating", "necessary for the activating phosphorylation", "for the activating phosphorylation of", "the activating phosphorylation of akt.", "activating phosphorylation of akt. akt1", "phosphorylation of akt. akt1 can", "of akt. akt1 can be", "akt. akt1 can be deactivated", "akt1 can be deactivated by", "can be deactivated by the", "be deactivated by the protein", "deactivated by the protein phosphatase", "by the protein phosphatase 2a", "protein phosphatase 2a pp2a", "2a pp2a complex", "pp2a complex that contains", "complex that contains a regulatory", "that contains a regulatory subunit", "contains a regulatory subunit b56", "a regulatory subunit b56 beta", "subunit b56 beta ppp2r5b", "beta ppp2r5b or", "ppp2r5b or b56 gamma", "or b56 gamma ppp2r5c", "b56 gamma ppp2r5c .", "gamma ppp2r5c . pi5p", "ppp2r5c . pi5p inhibits akt1", ". pi5p inhibits akt1 dephosphorylation", "pi5p inhibits akt1 dephosphorylation by", "inhibits akt1 dephosphorylation by pp2a", "akt1 dephosphorylation by pp2a through", "dephosphorylation by pp2a through an", "by pp2a through an unknown", "pp2a through an unknown mechanism", "an unknown mechanism ramel", "unknown mechanism ramel et", "mechanism ramel et al.", "ramel et al. 2009 .", "et al. 2009 . increased", "al. 2009 . increased pi5p", "2009 . increased pi5p levels", ". increased pi5p levels correlate", "increased pi5p levels correlate with", "pi5p levels correlate with inhibitory", "levels correlate with inhibitory phosphorylation", "correlate with inhibitory phosphorylation s", "inhibitory phosphorylation s of", "phosphorylation s of the", "s of the pp2a", "of the pp2a complex. mapk1", "pp2a complex. mapk1 erk2", "mapk1 erk2 and", "mapk3 erk1 are", "erk1 are involved in", "are involved in inhibitory phosphorylation", "involved in inhibitory phosphorylation of", "in inhibitory phosphorylation of pp2a", 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"cloned genes have been characterized", "have been characterized but", "been characterized but the", "characterized but the atp", "but the atp binding and", "the atp binding and hydrolyzing", "atp binding and hydrolyzing properties", "binding and hydrolyzing properties of", "and hydrolyzing properties of these", "hydrolyzing properties of these proteins", "properties of these proteins and", "of these proteins and complexes", "these proteins and complexes of", "proteins and complexes of them", "and complexes of them have", "complexes of them have not", "of them have not been", "them have not been determined." ] }, { "record_id": "GLY_000594_1_550", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "69017", "r hsa", "hsa 69017", "r hsa 69017" ] }, { "record_id": "GLY_000594_1_550", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cdk mediated", "mediated phosphorylation", "phosphorylation and", "and removal", "removal of", "of cdc6", "cdk mediated phosphorylation", "mediated phosphorylation and", "phosphorylation and removal", "and removal of", "removal of cdc6", "cdk mediated phosphorylation and", "mediated phosphorylation and removal", "phosphorylation and removal of", "and removal of cdc6", "cdk mediated phosphorylation and removal", "mediated phosphorylation and removal of", "phosphorylation and removal of cdc6", "as cells", "cells enter", "enter s", "s phase", "hscdc6p is", "is phosphorylated", "phosphorylated by", "by cdk", "cdk promoting", "promoting its", "its export", "export from", "from the", "the nucleus", "see bell", "bell and", "and dutta", "dutta 2002", "2002 .", "as cells enter", "cells enter s", "enter s phase", "phase hscdc6p", "hscdc6p is phosphorylated", "is phosphorylated by", "phosphorylated by cdk", "by cdk promoting", "cdk promoting its", "promoting its export", "its export from", "export from the", "from the nucleus", "nucleus see", "see bell and", "bell 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"human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "69231", "r hsa", "hsa 69231", "r hsa 69231" ] }, { "record_id": "GLY_000594_1_551", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cyclin d", "d associated", "associated events", "events in", "in g1", "cyclin d associated", "d associated events", "associated events in", "events in g1", "cyclin d associated events", "d associated events in", "associated events in g1", "cyclin d associated events in", "d associated events in g1", "three d", "d type", "type cyclins", "cyclins are", "are essential", "essential for", "for progression", "progression from", "from g1", "g1 to", "to s", "s phase.", "phase. these", "these d", "d cyclins", "cyclins bind", "bind to", "to and", "and activate", "activate both", "both cdk4", "cdk4 and", "and cdk6.", "cdk6. the", "the formation", "formation of", "all possible", "possible complexes", "complexes between", "between the", "the 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transition", "g2/m transition remove", "transition remove the", "remove the inhibitory phosphorylations", "the inhibitory phosphorylations and", "phosphorylations and together", "and together with", "together with the activating", "with the activating phosphorylation", "the activating phosphorylation mediated", "activating phosphorylation mediated by", "phosphorylation mediated by the", "mediated by the cak", "by the cak complex", "cak complex reviewed", "complex reviewed in", "reviewed in lolli and", "in lolli and johnson", "lolli and johnson 2005", "2005 enable", "enable the full activation", "the full activation of", "full activation of cdk1", "conde 2019 . ccna:cdk1", "2019 . ccna:cdk1 and", ". ccna:cdk1 and ccnb:cdk1", "ccna:cdk1 and ccnb:cdk1 complexes", "and ccnb:cdk1 complexes phosphorylate", "ccnb:cdk1 complexes phosphorylate a", "complexes phosphorylate a large", "phosphorylate a large number", "a large number of", "large number of proteins", "number of proteins involved", 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ccnb2 are ubiquitously", "ccnb2 are ubiquitously expressed", "ubiquitously expressed ccna1", "expressed ccna1 is", "ccna1 is predominantly expressed", "is predominantly expressed in", "predominantly expressed in the", "expressed in the testes", "in the testes and", "the testes and plays", "testes and plays an", "and plays an important", "plays an important role", "an important role in", "important role in meiosis", "in meiosis reviewed", "meiosis reviewed in", "reviewed in chotiner et", "in chotiner et al.", "chotiner et al. 2019", "2019 but", "but it is also", "it is also implicated", "is also implicated in", "also implicated in mitosis", "implicated in mitosis in", "in mitosis in specific", "mitosis in specific cell", "in specific cell types", "cell types such", "types such as", "such as hematopoietic stem", "as hematopoietic stem cells", "stem cells reviewed", "cells reviewed in", "reviewed in dai et", "in dai et al.", "dai et al. 2019", "et al. 2019 .", "al. 2019 . ccnb3", "2019 . ccnb3 functions", ". ccnb3 functions exclusively", "ccnb3 functions exclusively in", "functions exclusively in meiosis", "cell cycle progression is regulated", "cycle progression is regulated by", "progression is regulated by activation", "is regulated by activation of", "regulated by activation of cyclin", "by activation of cyclin dependent", "activation of cyclin dependent protein", "of cyclin dependent protein kinases", "cyclin dependent protein kinases at", "dependent protein kinases at g1/s", "kinases at g1/s s/g2", "g1/s s/g2 and", "s/g2 and g2/m transitions", "and g2/m transitions reviewed", "g2/m transitions reviewed in", "transitions reviewed in lemmens", "reviewed in lemmens and lindqvist", "in lemmens and lindqvist 2019", "lemmens and lindqvist 2019 .", "and lindqvist 2019 . completion", "lindqvist 2019 . completion of", "2019 . completion of dna", ". completion of dna replication", "completion of dna replication at", "of dna replication at the", "dna replication at the 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promotes the activation", "then promotes the activation of", "promotes the activation of cyclin", "the activation of cyclin b:cdk1", "of cyclin b:cdk1 ccnb:cdk1", "b:cdk1 ccnb:cdk1 complexes", "ccnb:cdk1 complexes reviewed", "complexes reviewed in pintard", "reviewed in pintard and archambault", "in pintard and archambault 2018", "and archambault 2018 lemmens", "archambault 2018 lemmens and", "2018 lemmens and lindqvist", "and lindqvist 2019 moura", "lindqvist 2019 moura and", "2019 moura and conde", "moura and conde 2019 .", "and conde 2019 . inhibitory", "conde 2019 . inhibitory pkmyt1", "2019 . inhibitory pkmyt1 and", ". inhibitory pkmyt1 and wee1", "inhibitory pkmyt1 and wee1 kinases", "pkmyt1 and wee1 kinases prevent", "and wee1 kinases prevent premature", "wee1 kinases prevent premature activation", "kinases prevent premature activation of", "prevent premature activation of cdk1", "premature activation of cdk1 complexes", "of cdk1 complexes reviewed", "cdk1 complexes reviewed in", "complexes reviewed in lemmens", "and lindqvist 2019 . the", "lindqvist 2019 . the cdc25", "2019 . the cdc25 family", ". the cdc25 family phosphatases", "cdc25 family phosphatases cdc25a", "phosphatases cdc25a cdc25b", "cdc25a cdc25b and", "and cdc25c activated", "cdc25c activated at", "at g2/m transition remove", "g2/m transition remove the", "transition remove the inhibitory", "remove the inhibitory phosphorylations and", "inhibitory phosphorylations and together", "phosphorylations and together with", "and together with the", "together with the activating phosphorylation", "with the activating phosphorylation mediated", "the activating phosphorylation mediated by", "activating phosphorylation mediated by the", "phosphorylation mediated by the cak", "mediated by the cak complex", "the cak complex reviewed", "cak complex reviewed in", "complex reviewed in lolli", "reviewed in lolli and johnson", "in lolli and johnson 2005", "johnson 2005 enable", "2005 enable the", "enable the full activation of", "the full activation of cdk1", "full activation of cdk1 complexes", "and conde 2019 . ccna:cdk1", "conde 2019 . ccna:cdk1 and", "2019 . ccna:cdk1 and ccnb:cdk1", ". ccna:cdk1 and ccnb:cdk1 complexes", "ccna:cdk1 and ccnb:cdk1 complexes phosphorylate", "and ccnb:cdk1 complexes phosphorylate a", "ccnb:cdk1 complexes phosphorylate a large", "complexes phosphorylate a large number", "phosphorylate a large number of", "a large number of proteins", "large number of proteins involved", "number of proteins involved in", "of proteins involved in mitosis", "involved in mitosis m", "in mitosis m phase", "m phase reviewed", "phase reviewed in", "reviewed in sefton 2001", "2001 including lamins", "including lamins reviewed in", "lamins reviewed in lemmens", "and lindqvist 2019 liu", "lindqvist 2019 liu and", "2019 liu and ikegami", "and ikegami 2020 and", "ikegami 2020 and other", "2020 and other proteins", "and other proteins involved in", "other proteins involved in nuclear", "proteins involved in nuclear envelope", "involved in nuclear envelope breakdown", "nuclear envelope breakdown reviewed", "envelope breakdown reviewed in", "breakdown reviewed in lindqvist", "reviewed in lindqvist et al.", "in lindqvist et al. 2009", "et al. 2009 lacroix", "al. 2009 lacroix et", "2009 lacroix et al.", "al. 2022 proteins", "2022 proteins involved", "proteins involved in mitotic spindle", "involved in mitotic spindle formation", "mitotic spindle formation reviewed", "spindle formation reviewed in", "formation reviewed in hayward", "reviewed in hayward et al.", "in hayward et al. 2019", "et al. 2019 lacroix", "al. 2019 lacroix et", "2019 lacroix et al.", "al. 2022 and", "2022 and proteins", "and proteins involved in disassembly", "proteins involved in disassembly of", "involved in disassembly of the", "in disassembly of the golgi", "disassembly of the golgi apparatus", "the golgi apparatus reviewed", "golgi apparatus reviewed in", "apparatus reviewed in preisinger", "reviewed in preisinger and barr", "in preisinger and barr 2005", "preisinger and barr 2005 .", "and barr 2005 . while", "barr 2005 . while cdk1", "2005 . while cdk1 complexes", ". while cdk1 complexes may", "while cdk1 complexes may exhibit", "cdk1 complexes may exhibit a", "complexes may exhibit a high", "may exhibit a high level", "exhibit a high level of", "a high level of redundancy", "high level of redundancy in", "level of redundancy in vitro", "redundancy in vitro bellanger", "in vitro bellanger et", "vitro bellanger et al.", "al. 2007 their", "2007 their substrate", "their substrate specificity in vivo", "substrate specificity in vivo is", "specificity in vivo is partially", "in vivo is partially determined", "vivo is partially determined by", "is partially determined by their", "partially determined by their subcellular", "determined by their subcellular localization", "their subcellular localization with", "subcellular localization with ccna:cdk1", "localization with ccna:cdk1 complexes", "with ccna:cdk1 complexes being mainly", "ccna:cdk1 complexes being mainly nuclear", "being mainly nuclear the", "mainly nuclear the ccnb1:cdk1", "nuclear the ccnb1:cdk1 complex", "the ccnb1:cdk1 complex being mainly", "ccnb1:cdk1 complex being mainly cytosolic", "being mainly cytosolic and", "mainly cytosolic and the", "cytosolic and the ccnb2:cdk1", "and the ccnb2:cdk1 complex localizing", "the ccnb2:cdk1 complex localizing mainly", "ccnb2:cdk1 complex localizing mainly to", "complex localizing mainly to the", "localizing mainly to the golgi", "mainly to the golgi membrane", "the golgi membrane jackman", "golgi membrane jackman et", "membrane jackman et al.", "et al. 1995 hagting", "al. 1995 hagting et", "1995 hagting et al.", "et al. 1999 dravian", "al. 1999 dravian et", "1999 dravian et al.", "et al. 2001 reviewed", "al. 2001 reviewed in", "2001 reviewed in yang", "reviewed in yang and kornbluth", "in yang and kornbluth 1999", "yang and kornbluth 1999 .", "and kornbluth 1999 . in", "kornbluth 1999 . in addition", ". in addition while", "in addition while ccna2", "ccna2 ccnb1 and", "ccnb1 and ccnb2 are", "and ccnb2 are ubiquitously expressed", "are ubiquitously expressed ccna1", "ubiquitously expressed ccna1 is", "expressed ccna1 is predominantly", "ccna1 is predominantly expressed in", "is predominantly expressed in the", "predominantly expressed in the testes", "expressed in the testes and", "in the testes and plays", "the testes and plays an", "testes and plays an important", "and plays an important role", "plays an important role in", "an important role in meiosis", "role in meiosis reviewed", "in meiosis reviewed in", "meiosis reviewed in chotiner", "reviewed in chotiner et al.", "in chotiner et al. 2019", "al. 2019 but", "2019 but it", "but it is also implicated", "it is also implicated in", "is also implicated in mitosis", "also implicated in mitosis in", "implicated in mitosis in specific", "in mitosis in specific cell", "mitosis in 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via electron transport to", "via electron transport to yield", "electron transport to yield additional", "transport to yield additional atp", "yield additional atp while", "additional atp while under", "atp while under anaerobic", "while under anaerobic conditions or", "under anaerobic conditions or in", "anaerobic conditions or in cells", "conditions or in cells lacking", "or in cells lacking mitochondria", "in cells lacking mitochondria nad+", "cells lacking mitochondria nad+ can", "lacking mitochondria nad+ can be", "mitochondria nad+ can be regenerated", "nad+ can be regenerated via", "can be regenerated via the", "be regenerated via the reduction", "regenerated via the reduction of", "via the reduction of pyruvate", "the reduction of pyruvate to", "reduction of pyruvate to lactate." ] }, { "record_id": "GLY_000594_1_559", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "70221", "r hsa", "hsa 70221", "r hsa 70221" ] }, { 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glycogen", ".

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enzymes", ".

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enzymes in", ".

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glycogen can", "1976 .

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enzymes", "gaa .

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glycogen", "hers 1976 .

glycogen can also", "1976 .

glycogen can also be", ".

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. they", ". they are", "they are major", "are major constituents", "major constituents of", "constituents of muscle", "of muscle protein.", "muscle protein. the", "protein. the breakdown", "the breakdown of", "breakdown of these", "of these amino", "these amino acids", "amino acids starts", "acids starts with", "starts with two", "with two common", "two common steps", "common steps catalyzed", "steps catalyzed by", "catalyzed by enzymes", "by enzymes that", "enzymes that act", "that act on", "act on all", "on all three", "all three amino", "three amino acids:", "amino acids: reversible", "acids: reversible transamination", "reversible transamination by", "transamination by branched", "by branched chain", "amino acid aminotransferase", "aminotransferase and", "and irreversible oxidative", "irreversible oxidative decarboxylation", "oxidative decarboxylation by", "decarboxylation by the", "by the branched", "branched chain ketoacid", "chain ketoacid dehydrogenase", "ketoacid dehydrogenase 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oxidized via", "fully oxidized via the", "oxidized via the citric", "via the citric acid", "the citric acid cycle", "acid cycle in", "cycle in liver", "in liver they can", "liver they can be", "they can be directed", "can be directed toward", "be directed toward the", "directed toward the synthesis", "toward the synthesis of", "the synthesis of ketone", "synthesis of ketone bodies", "ketone bodies acetoacetate", "bodies acetoacetate and", "acetoacetate and acetyl coa", "coa and glucose", "and glucose succinyl", "glucose succinyl coa", "coa neinast", "neinast et al. 2019", "et al. 2019 .", "the branched chain amino acids", "chain amino acids leucine", "acids leucine isoleucine", "leucine isoleucine and", "and valine are all", "valine are all essential", "are all essential amino acids", "essential amino acids i.e.", "acids i.e. ones", "i.e. ones required in", "ones required in the diet", "required in the diet .", "in the diet . they", "the diet . they are", "diet . they are major", ". they are major constituents", "they are major constituents of", "are major constituents of muscle", "major constituents of muscle protein.", "constituents of muscle protein. the", "of muscle protein. the breakdown", "muscle protein. the breakdown of", "protein. the breakdown of these", "the breakdown of these amino", "breakdown of these amino acids", "of these amino acids starts", "these amino acids starts with", "amino acids starts with two", "acids starts with two common", "starts with two common steps", "with two common steps catalyzed", "two common steps catalyzed by", "common steps catalyzed by enzymes", "steps catalyzed by enzymes that", "catalyzed by enzymes that act", "by enzymes that act on", "enzymes that act on all", "that act on all three", "act on all three amino", "on all three amino acids:", "all three amino acids: reversible", "three amino acids: reversible transamination", "amino acids: reversible transamination by", "acids: reversible transamination by branched", "reversible transamination by branched chain", "transamination by branched chain amino", "by branched chain amino acid", "branched chain amino acid aminotransferase", "amino acid aminotransferase and", "acid aminotransferase and irreversible", "aminotransferase and irreversible oxidative", "and irreversible oxidative decarboxylation by", "irreversible oxidative decarboxylation by the", "oxidative decarboxylation by the branched", "decarboxylation by the branched chain", "by the branched chain ketoacid", "the branched chain ketoacid dehydrogenase", "branched chain ketoacid dehydrogenase complex.", "chain ketoacid dehydrogenase complex. isovaleryl", "ketoacid dehydrogenase complex. isovaleryl coa", "dehydrogenase complex. isovaleryl coa is", "complex. isovaleryl coa is produced", "isovaleryl coa is produced from", "coa is produced from leucine", "is produced from leucine by", "produced from leucine by these", "from leucine by these two", "leucine by these two reactions", "these two reactions alpha", "two reactions alpha methylbutyryl", "reactions alpha methylbutyryl coa", "alpha methylbutyryl coa from isoleucine", "coa from isoleucine and", "from isoleucine and isobutyryl", "isoleucine and isobutyryl coa", "and isobutyryl coa from valine.", "isobutyryl coa from valine. these", "coa from valine. these acyl", "from valine. these acyl coa's", "valine. these acyl coa's undergo", "these acyl coa's undergo dehydrogenation", "coa's undergo dehydrogenation catalyzed", "undergo dehydrogenation catalyzed by", "dehydrogenation catalyzed by three", "catalyzed by three different but", "by three different but related", "three different but related enzymes", "but related enzymes and", "related enzymes and the", "enzymes and the breakdown", "and the breakdown pathways then", "the breakdown pathways then diverge.", "breakdown pathways then diverge. leucine", "pathways then diverge. leucine is", "then diverge. leucine is ultimately", "diverge. leucine is ultimately converted", "leucine is ultimately converted to", "is ultimately converted to acetyl", "ultimately converted to acetyl coa", "converted to acetyl coa and", "to acetyl coa and acetoacetate", "coa and acetoacetate isoleucine", "and acetoacetate isoleucine to", "acetoacetate isoleucine to acetyl", "isoleucine to acetyl coa and", "to acetyl coa and succinyl", "acetyl coa and succinyl coa", "and succinyl coa and", "succinyl coa and valine", "coa and valine to", "and valine to succinyl coa.", "valine to succinyl coa. under", "to succinyl coa. under fasting", "succinyl coa. under fasting conditions", "under fasting conditions substantial", "fasting conditions substantial amounts", "conditions substantial amounts of", "substantial amounts of all three", "amounts of all three amino", "of all three amino acids", "all three amino acids are", "three amino acids are generated", "amino acids are generated by", "acids are generated by protein", "are generated by protein breakdown.", "generated by protein breakdown. in", "by protein breakdown. in muscle", "breakdown. in muscle the", "in muscle the final", "muscle the final products", "the final products of leucine", "products of leucine isoleucine", "isoleucine and valine catabolism", "and valine catabolism can be", "valine catabolism can be fully", "catabolism can be fully oxidized", "can be fully oxidized via", "be fully oxidized via the", "fully oxidized via the citric", "oxidized via the citric acid", "via the citric acid cycle", "citric acid cycle in", "acid cycle in liver", "cycle in liver they", "in liver they can be", "liver they can be directed", "they can be directed toward", "can be directed toward the", "be directed toward the synthesis", "directed toward the synthesis of", "toward the synthesis of ketone", "the synthesis of ketone bodies", "of ketone bodies acetoacetate", "ketone bodies acetoacetate and", "bodies acetoacetate and acetyl", "and acetyl coa and", "acetyl coa and glucose", "and glucose succinyl coa", "succinyl coa neinast", "coa neinast et", "neinast et al. 2019 ." ] }, { "record_id": "GLY_000594_1_563", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "70921", "r hsa", "hsa 70921", "r hsa 70921" ] }, { "record_id": "GLY_000594_1_563", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "histidine catabolism", "the major", "major pathway", "pathway of", "of histidine", "annotated here", "proceeds in", "in four", "four steps", "steps to", "to yield", "yield glutamate", "glutamate and", "in the", "the process", "convert one", "one molecule", "molecule of", "of tetrahydrofolate", "tetrahydrofolate to", "to 5", "5 formiminotetrahydrofolate", "morris et", "et al.", "al. 1972", "1972 .", ". histidine", "histidine can", "can also", "also be", "be decarboxylated", "decarboxylated to", "to form", "form histamine.", "histamine. histidine", "be used", "used to", "form carnosine", "beta alanyl", "alanyl l", "l histidine", "an abundant", "abundant dipeptide", "dipeptide in", "in skeletal", "skeletal muscle", "muscle and", "and brain", "brain of", "of most", "most vertebrates.", "the major pathway", "major pathway of", "pathway of histidine", "of histidine catabolism", "catabolism annotated", "here proceeds", "proceeds in four", "in four steps", "four steps to", "steps to yield", "to yield glutamate", "yield glutamate and", "and in", "in the process", "process convert", "convert one molecule", "one molecule of", "molecule of tetrahydrofolate", "of tetrahydrofolate to", "tetrahydrofolate to 5", "to 5 formiminotetrahydrofolate", "formiminotetrahydrofolate morris", "morris et al.", "et al. 1972", "al. 1972 .", "1972 . histidine", ". histidine can", "histidine can also", "can also be", "also be decarboxylated", "be decarboxylated to", "decarboxylated to form", "to form histamine.", "form histamine. histidine", "histamine. histidine can", "also be used", "be used to", "used to form", "to form carnosine", "carnosine beta", "beta alanyl l", "alanyl l histidine", "an abundant dipeptide", "abundant dipeptide in", "dipeptide in skeletal", "in skeletal muscle", "skeletal muscle and", "muscle and brain", "and brain of", "brain of most", "of most vertebrates.", "the major pathway of", "major pathway of histidine", "pathway of histidine catabolism", "histidine catabolism annotated", "catabolism annotated here", "annotated here proceeds", "here proceeds in", "proceeds in four steps", "in four steps to", "four steps to yield", "steps to yield glutamate", "to yield glutamate and", "glutamate and in", "and in the", "the process convert", "process convert one", "convert one molecule of", "one molecule of tetrahydrofolate", "molecule of tetrahydrofolate to", "of tetrahydrofolate to 5", "tetrahydrofolate to 5 formiminotetrahydrofolate", "5 formiminotetrahydrofolate morris", "formiminotetrahydrofolate morris et", "morris et al. 1972", "et al. 1972 .", "al. 1972 . histidine", "1972 . histidine can", ". histidine can also", "histidine can also be", "can also be decarboxylated", "also be decarboxylated to", "be decarboxylated to form", "decarboxylated to form histamine.", "to form histamine. histidine", "form histamine. histidine can", "histamine. histidine can also", "can also be used", "also be used to", "be used to form", "used to form carnosine", "form carnosine beta", "carnosine beta alanyl", "beta alanyl l histidine", "histidine an", "an abundant dipeptide in", "abundant dipeptide in skeletal", "dipeptide in skeletal muscle", "in skeletal muscle and", "skeletal muscle and brain", "muscle and brain of", "and brain of most", "brain of most vertebrates.", "the major pathway of histidine", "major pathway of histidine catabolism", "of histidine catabolism annotated", "histidine catabolism annotated here", "annotated here proceeds in", "here proceeds in four", "proceeds in four steps to", "in four steps to yield", "four steps to yield glutamate", "steps to yield 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freeman 2001", "freeman 2001 .", "in humans most", "humans most catabolism", "most catabolism of l", "catabolism of l lysine", "of l lysine normally", "l lysine normally proceeds", "lysine normally proceeds via", "normally proceeds via a", "proceeds via a sequence", "via a sequence of", "a sequence of seven", "sequence of seven reactions", "of seven reactions which", "seven reactions which feeds", "reactions which feeds into", "which feeds into the", "feeds into the pathway", "into the pathway for", "the pathway for fatty", "pathway for fatty acid", "for fatty acid catabolism.", "fatty acid catabolism. in", "acid catabolism. in the", "catabolism. in the first", "in the first two", "the first two reactions", "two reactions catalyzed", "reactions catalyzed by", "catalyzed by a single", "by a single enzyme", "a single enzyme complex", "enzyme complex lysine", "complex lysine is", "lysine is combined with", "is combined with alpha", "combined with alpha ketoglutarate", "with alpha 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the conversion", "responsible for the conversion of", "for the conversion of alpha", "the conversion of alpha ketoglutarate", "conversion of alpha ketoglutarate to", "of alpha ketoglutarate to succinyl", "alpha ketoglutarate to succinyl coa", "ketoglutarate to succinyl coa in", "to succinyl coa in the", "succinyl coa in the citric", "coa in the citric acid", "in the citric acid cycle", "acid cycle yielding", "cycle yielding glutaryl", "yielding glutaryl coa. glutaryl coa", "glutaryl coa. glutaryl coa is", "coa. glutaryl coa is converted", "glutaryl coa is converted to", "coa is converted to crotonyl", "is converted to crotonyl coa", "to crotonyl coa crotonyl", "crotonyl coa crotonyl coa", "coa crotonyl coa is", "crotonyl coa is converted to", "coa is converted to beta", "is converted to beta hydroxybutyryl", "converted to beta hydroxybutyryl coa", "beta hydroxybutyryl coa and", "hydroxybutyryl coa and beta", "coa and beta hydroxybutyryl", "and beta hydroxybutyryl coa is", "beta hydroxybutyryl coa is converted", "hydroxybutyryl coa is converted to", "coa is converted to acetoacetyl", "is converted to acetoacetyl coa.", "converted to acetoacetyl coa. the", "to acetoacetyl coa. the products", "acetoacetyl coa. the products of", "coa. the products of lysine", "the products of lysine catabolism", "products of lysine catabolism are", "of lysine catabolism are thus", "lysine catabolism are thus exclusively", "catabolism are thus exclusively ketogenic", "thus exclusively ketogenic i.e.", "ketogenic i.e. under", "i.e. under starvation conditions", "under starvation conditions they can", "starvation conditions they can be", "conditions they can be used", "they can be used for", "can be used for the", "be used for the synthesis", "used for the synthesis of", "for the synthesis of ketone", "the synthesis of ketone bodies", "of ketone bodies beta", "ketone bodies beta hydroxybutyrate", "bodies beta hydroxybutyrate and", "hydroxybutyrate and acetoacetate but", "and acetoacetate but not", "acetoacetate but not for", "but not for the net", "not for the net synthesis", "for the net synthesis of", "the net synthesis of glucose", "synthesis of glucose cox", "of glucose cox 2001", "cox 2001 goodman and", "2001 goodman and freeman", "goodman and freeman 2001 ." ] }, { "record_id": "GLY_000594_1_565", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71240", "r hsa", "hsa 71240", "r hsa 71240" ] }, { "record_id": "GLY_000594_1_565", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tryptophan catabolism", "tryptophan is", "is catabolized", "catabolized in", "in seven", "seven steps", "steps to", "to yield", "yield aminomuconate.", "aminomuconate. intermediates", "intermediates in", "in this", "this process", "process are", "are also", "also used", "used in", "in the", "the synthesis", "synthesis of", "of serotonin", "serotonin and", "and kynurenine", "peters 1991", "1991 .", "tryptophan is catabolized", "is catabolized in", "catabolized in seven", "in seven steps", "seven steps to", "steps to yield", "to yield aminomuconate.", "yield aminomuconate. intermediates", "aminomuconate. intermediates in", "intermediates in this", "in this process", "this process are", "process are also", "are also used", "also used in", "used in the", "in the synthesis", "the synthesis of", "synthesis of serotonin", "of serotonin and", "serotonin and kynurenine", "kynurenine peters", "peters 1991 .", "tryptophan is catabolized in", "is catabolized in seven", "catabolized in seven steps", "in seven steps to", "seven steps to yield", "steps to yield aminomuconate.", "to yield aminomuconate. intermediates", "yield aminomuconate. intermediates in", "aminomuconate. intermediates in this", "intermediates in this process", "in this process are", "this process are also", "process are also used", "are also used in", "also used in the", "used in the synthesis", "in the synthesis of", "the synthesis of serotonin", "synthesis of serotonin and", "of serotonin and kynurenine", "and kynurenine peters", "kynurenine peters 1991", "tryptophan is catabolized in seven", "is catabolized in seven steps", "catabolized in seven steps to", "in seven steps to yield", "seven steps to yield aminomuconate.", "steps to yield aminomuconate. intermediates", "to yield aminomuconate. intermediates in", "yield aminomuconate. intermediates in this", "aminomuconate. intermediates in this process", "intermediates in this process are", "in this process are also", "this process are also used", "process are also used in", "are also used in the", "also used in the synthesis", "used in the synthesis of", "in the synthesis of serotonin", "the synthesis of serotonin and", "synthesis of serotonin and kynurenine", "serotonin and kynurenine peters", "and kynurenine peters 1991", "kynurenine peters 1991 ." ] }, { "record_id": "GLY_000594_1_566", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71403", "r hsa", "hsa 71403", "r hsa 71403" ] }, { "record_id": "GLY_000594_1_566", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "citric acid", "acid cycle", "tca cycle", "citric acid cycle", "cycle tca", "acid cycle tca", "cycle tca cycle", "citric acid cycle tca", "acid cycle tca cycle", "in the", "the citric", "acid or", "or tricarboxylic", "tricarboxylic acid", "the acetyl", "acetyl group", "group of", "of acetyl", "acetyl coa", "derived primarily", "primarily from", "from oxidative", "oxidative decarboxylation", "decarboxylation of", "of pyruvate", "beta oxidation", "oxidation of", "of long", "long chain", "chain fatty", "fatty acids", "and catabolism", "catabolism of", "of ketone", "ketone bodies", "bodies and", "and several", "several amino", "amino acids", "can be", "be completely", "completely oxidized", "oxidized to", "to co2", "co2 in", "in reactions", "reactions that", "that 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eight", "mitochondrion.

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the", "annotated.

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eight", "the mitochondrion.

eight canonical", "mitochondrion.

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the cyclical nature of", "annotated.

the cyclical nature of the", "cyclical nature of the reactions", "nature of the reactions responsible", "of the reactions responsible for", "the reactions responsible for the", "reactions responsible for the oxidation", "responsible for the oxidation of", "for the oxidation of acetate", "the oxidation of acetate was", "oxidation of acetate was first", "of acetate was first suggested", "acetate was first suggested by", "was first suggested by hans", "first suggested by hans krebs", "suggested by hans krebs from", "by hans krebs from biochemical", "hans krebs from biochemical studies", "krebs from biochemical studies of", "from biochemical studies of pigeon", "biochemical studies of pigeon breast", "studies of pigeon breast muscle", "pigeon breast muscle krebs", "breast muscle krebs et", "muscle krebs et al.", "krebs et al. 1938", "al. 1938 krebs", "1938 krebs and eggleston", "krebs and eggleston 1940", "and eggleston 1940 .", "eggleston 1940 . ochoa", "1940 . ochoa and colleagues", ". ochoa and colleagues studied", "ochoa and colleagues studied many", "and colleagues studied many molecular", "colleagues studied many molecular details", "studied many molecular details of", "many molecular details of individual", "molecular details of individual reactions", "of individual reactions mainly", "individual reactions mainly by", "reactions mainly by studying", "mainly by studying enzymes purified", "by studying enzymes purified from", "studying enzymes purified from pig", "enzymes purified from pig hearts", "from pig hearts ochoa", "hearts ochoa 1980", "ochoa 1980 . while", "1980 . while the human", ". while the human homologs", "while the human homologs of", "the human homologs of these", "human homologs of these enzymes", "homologs of these enzymes have", "of these enzymes have all", "these enzymes have all been", "enzymes have all been identified", "all been identified their", "been identified their biochemical", "identified their biochemical characterization", "biochemical characterization has in", "characterization has in general", "in general been limited", "been limited and many", "limited and many molecular", "and many molecular details of", "many molecular details of the", "molecular details of the human", "details of the human reactions", "of the human reactions are", "the human reactions are inferred", "human reactions are inferred from", "reactions are inferred from those", "are inferred from those worked", "inferred from those worked out", "from those worked out in", "those worked out in studies", "worked out in studies of", "out in studies of the", "in studies of the model", "studies of the model systems.", "of the model systems. studies", "the model systems. studies examining", "model systems. studies examining the", "systems. studies examining the impact", "studies examining the impact of", "examining the impact of elevated", "the impact of elevated citric", "impact of elevated citric acid", "of elevated citric acid cycle", "elevated citric acid cycle intermediates", "citric acid cycle intermediates such", "acid cycle intermediates such as", "cycle intermediates such as succinate", "intermediates such as succinate and", "such as succinate and fumarate", "as succinate and fumarate led", "succinate and fumarate led to", "and fumarate led to the", "fumarate led to the recognition", "led to the recognition of", "to the recognition of the", "the recognition of the role", "recognition of the role of", "of the role of metabolites", "the role of metabolites in", "role of metabolites in driving", "of metabolites in driving cancer", "metabolites in driving cancer progression", "driving cancer progression 'oncometabolites'", "'oncometabolites' pollard et", "pollard et al. 2005", "al. 2005 reviewed", "2005 reviewed in hayashi", "reviewed in hayashi et al.", "hayashi et al. 2018", "et al. 2018 .", "al. 2018 . the", "2018 . the role of", ". the role of tca", "the role of tca enzymes", "role of tca enzymes in", "of tca enzymes in disease", "tca enzymes in disease was", "enzymes in disease was reviewed", "in disease was reviewed by", "disease was reviewed by kang", "was reviewed by kang et", "reviewed by kang et al.", "kang et al. 2021." ] }, { "record_id": "GLY_000594_1_567", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72086", "r hsa", "hsa 72086", "r hsa 72086" ] }, { "record_id": "GLY_000594_1_567", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna capping", "the 5'", "5' ends", "ends of", "of all", "all eukaryotic", "eukaryotic pre", "pre mrnas", "mrnas studied", "studied thus", "thus far", "far are", "are converted", "converted to", "to cap", "cap structures.", "structures. the", "the cap", "cap is", "is thought", "thought to", "to influence", "influence splicing", "splicing of", "of the", "the first", "first intron", "and is", "is bound", "bound by", "by 'cap", "'cap binding'", "binding' 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the", "export to the cytoplasm.
the capping", "to the cytoplasm.
the capping reaction", "the cytoplasm.
the capping reaction usually", "cytoplasm.
the capping reaction usually occurs", "capping reaction usually occurs very", "reaction usually occurs very rapidly", "usually occurs very rapidly on", "occurs very rapidly on nascent", "very rapidly on nascent transcripts", "on nascent transcripts after", "nascent transcripts after the", "transcripts after the synthesis", "after the synthesis of only", "the synthesis of only a", "synthesis of only a few", "of only a few nucleotides", "only a few nucleotides by", "a few nucleotides by rna", "few nucleotides by rna polymerase", "nucleotides by rna polymerase ii.", "by rna polymerase ii. the", "rna polymerase ii. the capping", "polymerase ii. the capping reaction", "ii. the capping reaction involves", "the capping reaction involves the", "capping reaction involves the conversion", "reaction involves the conversion of", "involves the conversion of the", "the conversion of the 5'", "conversion of the 5' end", "of the 5' end of", "the 5' end of the", "5' end of the nascent", "end of the nascent transcript", "of the nascent transcript from", "the nascent transcript from a", "nascent transcript from a triphosphate", "transcript from a triphosphate to", "from a triphosphate to a", "a triphosphate to a diphosphate", "triphosphate to a diphosphate by", "to a diphosphate by a", "a diphosphate by a rna", "diphosphate by a rna 5'", "by a rna 5' triphosphatase", "rna 5' triphosphatase followed", "5' triphosphatase followed by", "triphosphatase followed by the", "followed by the addition of", "by the addition of a", "the addition of a guanosine", "addition of a guanosine monophosphate", "of a guanosine monophosphate by", "a guanosine monophosphate by the", "guanosine monophosphate by the mrna", "monophosphate by the mrna guanylyltransferase", "the mrna guanylyltransferase to", "mrna guanylyltransferase to form", "guanylyltransferase to form a", "to form a 5' 5'", "form a 5' 5' triphosphate", "a 5' 5' triphosphate linkage.", "5' 5' triphosphate linkage. this", "5' triphosphate linkage. this cap", "triphosphate linkage. this cap is", "linkage. this cap is then", "this cap is then methylated", "cap is then methylated by", "is then methylated by 2'", "then methylated by 2' o", "methylated by 2' o methyltransferases.

" ] }, { "record_id": "GLY_000594_1_568", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72163", "r hsa", "hsa 72163", "r hsa 72163" ] }, { "record_id": "GLY_000594_1_568", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna splicing", "major pathway", "splicing major", "mrna splicing major", "splicing major pathway", "eukaryotic genes", "genes are", "are transcribed", "transcribed to", "to yield", "yield pre", "pre mrnas", "mrnas that", "that are", "are processed", "processed to", "to add", "add methyl", "methyl guanosine", "guanosine cap", "cap structures", "structures and", "and polyadenylate", "polyadenylate tails", "tails and", "and to", "to splice", "splice together", "together segments", "segments of", "of a", "a pre", "pre mrna", "mrna termed", "termed exons", "thereby removing", "removing segments", "segments termed", "termed introns.", "introns. more", "more than", "than 90%", "90% of", "of human", "human genes", "genes contain", "contain introns", "with an", "an average", "average of", "of 4.0", "4.0 introns", "introns per", "per gene", "gene and", "and 3413", "3413 nucleotides", "nucleotides per", "per intron", "intron compared", "compared with", "with 5.0", "5.0 exons", "exons per", "and 50.9", "50.9 nucleotides", "per exon", "deutsch and", "and long", "long 1999", "1999 .", "notable exceptions", "exceptions are", "are the", "the histone", "histone genes", "which are", "are intronless.", "
pre mrna", "splicing is", "is performed", "performed by", "by a", "a large", "large ribonucleoprotein", "ribonucleoprotein complex", "the spliceosome", "which contains", "contains 5", "5 small", "small nuclear", "nuclear rnas", "and more", "than 150", "150 proteins", "reviewed in", "in will", "will and", "and luhrmann", "luhrmann 2011", "kastner et", "et al.", "al. 2019", "yan et", "fica et", "al. 2020", "wan et", "wilkinson et", "2020 .", ". the", "the catalyst", "catalyst in", "in the", "spliceosome comprises", "comprises magnesium", "magnesium ions", "ions coordinated", "coordinated by", "by the", "the u6", "u6 snrna", "snrna that", "that catalyze", "catalyze transesterification", "transesterification reactions", "reactions between", "between hydroxyl", "hydroxyl groups", "groups and", "and phosphate", "phosphate groups", "groups from", "from the", "the pre", "pre mrna.", "mrna. the", "the role", "role of", "of the", "snrna demonstrates", "demonstrates that", "that the", "spliceosome is", "is a", "a ribozyme", "ribozyme hints", "hints at", "at the", "the origin", "origin of", "spliceosome as", "as a", "a self", "self splicing", "splicing group", "group ii", "ii intron.", "intron.
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et", "al. 2011", "haselbach et", "busetto et", ". dissociation", "the sf3a", "sf3a and", "and sf3b", "sf3b subcomplexes", "subcomplexes of", "snrnp allows", "allows the", "intron branch", "point to", "to dock", "dock near", "near the", "forming the", "the b*", "b* spliceosomal", "spliceosomal complex.", "complex. reaction", "reaction of", "point at", "yields the", "spliceosomal c", "c complex", "jurica et", "reichert et", "gencheva et", "alexandrov et", "barbosa et", "steckelberg et", "point is", "is rotated", "rotated to", "to allow", "allow the", "site to", "to enter", "enter the", "yielding the", "spliceosomal c*", "c* complex", "ortlepp et", "zhou and", "and reed", "reed 1998", "ilagan et", ". reaction", "exon at", "site yields", "spliceosomal p", "zhou et", "tange et", "al. 2005", "zhang and", "and krainer", "krainer 2007", "p complex", "complex then", "then dissociates", "dissociates to", "yield an", "an mrnp", "mrnp containing", "the spliced", "and associated", "associated proteins", "including the", "the exon", "exon junction", "junction complex", "ohno and", "and shimura", "shimura 1996", "merz et", "yoshimoto et", "zanini et", "felisberto rodrigues", "rodrigues et", "ejc reviewed", "in schlautmann", "schlautmann and", "and gehring", "gehring 2020", "intron lariat", "lariat spliceosome", "intron lariat.", "lariat. the", "the ils", "ils is", "is then", "then disassembled", "disassembled to", "to free", "free its", "its components", "components for", "for further", "further splicing", "splicing reactions", "reactions and", "lariat is", "is degraded", "wen et", "studer et", "eukaryotic genes are", "genes are transcribed", "are transcribed to", "transcribed to yield", "to yield pre", "yield pre mrnas", "pre mrnas that", "mrnas that are", "that are processed", "are processed to", "processed to add", "to add methyl", "add methyl guanosine", "methyl guanosine cap", "guanosine cap structures", "cap structures and", "structures and polyadenylate", "and polyadenylate tails", "polyadenylate tails and", "tails and to", "and to splice", "to splice together", "splice together segments", "together segments of", "segments of a", "of a pre", "a pre mrna", "pre mrna termed", "mrna termed exons", "exons thereby", "thereby removing segments", "removing segments termed", "segments termed introns.", "termed introns. more", "introns. more than", "more than 90%", "than 90% of", "90% of human", "of human genes", "human genes contain", "genes contain introns", "introns with", "with an average", "an average of", "average of 4.0", "of 4.0 introns", "4.0 introns per", "introns per gene", "per gene and", "gene and 3413", "and 3413 nucleotides", "3413 nucleotides per", "nucleotides per intron", "per intron compared", "intron compared with", "compared with 5.0", "with 5.0 exons", "5.0 exons per", "exons per gene", "gene and 50.9", "and 50.9 nucleotides", "50.9 nucleotides per", "nucleotides per exon", "exon deutsch", "deutsch and long", "and long 1999", "long 1999 .", ". notable", "notable exceptions are", "exceptions are the", "are the histone", "the histone genes", "genes which", "which are intronless.", "intronless.
pre", "
pre mrna splicing", "mrna splicing is", "splicing is performed", "is performed by", "performed by a", "by a large", "a large ribonucleoprotein", "large ribonucleoprotein complex", "complex the", "spliceosome which", "which contains 5", "contains 5 small", "5 small nuclear", "small nuclear rnas", "rnas snrnas", "snrnas and", "and more than", "more than 150", "than 150 proteins", "proteins reviewed", "reviewed in will", "in will and", "will and luhrmann", "and luhrmann 2011", "2011 kastner", "kastner et al.", "et al. 2019", "2019 yan", "yan et al.", "2019 fica", "fica et al.", "et al. 2020", "2020 wan", "wan et al.", "2020 wilkinson", "wilkinson et al.", "al. 2020 .", "2020 . the", ". the catalyst", "the catalyst in", "catalyst in the", "in the spliceosome", "the spliceosome comprises", "spliceosome comprises magnesium", "comprises magnesium ions", "magnesium ions coordinated", "ions coordinated by", "coordinated by the", "by the u6", "the u6 snrna", "u6 snrna that", "snrna that catalyze", "that catalyze transesterification", "catalyze transesterification reactions", "transesterification reactions between", "reactions between hydroxyl", "between hydroxyl groups", "hydroxyl groups and", "groups and phosphate", "and phosphate groups", "phosphate groups from", "groups from the", "from the pre", "the pre mrna.", "pre mrna. the", "mrna. the role", "the role of", "role of the", "of the u6", "u6 snrna demonstrates", "snrna demonstrates that", "demonstrates that the", "that the spliceosome", "the spliceosome is", "spliceosome is a", "is a ribozyme", "a ribozyme hints", "ribozyme hints at", "hints at the", "at the origin", "the origin of", "origin of the", "of the spliceosome", "the spliceosome as", "spliceosome as a", "as a self", "a self splicing", "self splicing group", "splicing group ii", "group ii intron.", "ii intron.
the", "intron.
the spliceosome", "
the spliceosome is", "spliceosome is initially", "is initially assembled", "initially assembled cotranscriptionally", "assembled cotranscriptionally on", "cotranscriptionally on the", "on the pre", "the pre mrna", "pre mrna as", "mrna as the", "as the spliceosomal", "the spliceosomal e", "e early", "early complex", "complex and then", "and then remodelled", "then remodelled sequentially", "remodelled sequentially by", "sequentially by association", "by association and", "association and dissociation", "and dissociation of", "dissociation of proteins", "of proteins and", "proteins and snrnas", "and snrnas to", "snrnas to catalyze", "to catalyze of", "catalyze of the", "of the two", "the two reactions", "two reactions of", "reactions of splicing.", "of splicing. first", "first a", "a nucleophilic attack", "nucleophilic attack by", "attack by the", "by the 2'", "the 2' hydroxyl", "2' hydroxyl group", "hydroxyl group of", "group of a", "of a conserved", "a conserved adenine", "conserved adenine residue", "residue the", "the branch point", "point within", "within the intron", "the intron on", "intron on the", "on the phosphate", "the phosphate group", "phosphate group of", "group of the", "of the 5'", "the 5' residue", "5' residue of", "residue of the", "of the intron", "the intron yields", "intron yields a", "yields a lariat", "lariat looped", "looped structure", "structure in the", "in the intron", "the intron joined", "intron joined to", "joined to the", "to the downstream", "downstream 3'", "3' exon", "exon and a", "and a free", "a free upstream", "free upstream exon", "upstream exon with", "exon with a", "with a 3'", "a 3' hydroxyl", "3' hydroxyl group.", "hydroxyl group. second", "second a", "by the 3'", "the 3' hydroxyl", "3' hydroxyl group", "of the upstream", "the upstream exon", "upstream exon on", "exon on the", "the phosphate of", "phosphate of the", "of the downstream", "the downstream exon", "downstream exon yields", "exon yields a", "yields a spliced", "a spliced mrna", "spliced mrna containing", "mrna containing the", "containing the upstream", "upstream exon ligated", "exon ligated to", "ligated to the", "downstream exon and", "a free intron", "free intron containing", "intron containing a", "containing a lariat", "a lariat structure.", "lariat structure.
the", "structure.
the spliceosomal", "
the spliceosomal e", "spliceosomal e complex", "e complex contains", "complex contains the", "contains the u1", "the u1 snrnp", "u1 snrnp bound", "snrnp bound to", "bound to the", "to the 5'", "the 5' splice", "5' splice site", "site sf1", "sf1 bound to", "to the branch", "point and", "and the u2af", "the u2af complex", "u2af complex bound", "complex bound to", "to the polypyrimidine", "the polypyrimidine tract", "polypyrimidine tract of", "tract of the", "the intron and", "intron and the", "and the 3'", "the 3' splice", "3' splice site", "splice site of", "site of the", "of the pre", "mrna zhuang", "zhuang and weiner", "and weiner 1986", "1986 hong", "hong et al.", "et al. 1997", "1997 das", "das et al.", "et al. 2000", "2000 hartmuth", "hartmuth et al.", "et al. 2002", "2002 rappsilber", "rappsilber et al.", "2002 hegele", "hegele et al.", "et al. 2012", "2012 makarov", "makarov et al.", "2012 crisci", "crisci et al.", "et al. 2015", "2015 kondo", "kondo et al.", "2015 tan", "tan et al.", "et al. 2016", "al. 2016 .", "2016 . sf1", ". sf1 and", "sf1 and u2af", "and u2af are", "u2af are displaced", "are displaced on", "displaced on the", "pre mrna and", "mrna and the", "and the u2", "the u2 snrnp", "u2 snrnp binds", "snrnp binds the", "binds the branch", "the branch region", "branch region to", "region to yield", "to yield the", "yield the spliceosomal", "the spliceosomal a", "spliceosomal a complex", "complex wu", "wu and manley", "and manley 1989", "1989 fleckner", "fleckner et al.", "1997 neubauer", "neubauer et al.", "et al. 1998", "1998 hartmuth", "2002 xu", "xu et al.", "et al. 2004", "2004 behzadnia", "behzadnia et al.", "et al. 2007", "2007 shen", "shen et al.", "et al. 2008", "2008 chen", "chen et al.", "et al. 2017", "2017 zhang", "zhang et al.", ". the u4/u6.u5", "the u4/u6.u5 tri", "u4/u6.u5 tri snrnp", "snrnp containing", "containing the u4", "the u4 snrna", "u4 snrna base", "snrna base paired", "base paired with", "paired with the", "with the u6", "u6 snrna plus", "snrna plus the", "plus the u5", "the u5 snrnp", "u5 snrnp and", "snrnp and accessory", "and accessory proteins", "proteins binds", "binds the spliceosomal", "a complex to", "complex to form", "to form the", "form the spliceosomal", "the spliceosomal pre", "spliceosomal pre b", "pre b complex", "complex hausner", "hausner et al.", "et al. 1990", "1990 kataoka", "kataoka and dreyfuss", "and dreyfuss 2004", "2004 chi", "chi et al.", "et al. 2013", "2013 mohlmann", "mohlmann et al.", "et al. 2014", "2014 boesler", "boesler et al.", "2016 zhan", "zhan et al.", "et al. 2018", "2018 charenton", "charenton et al.", "2019 kastner", "2019 townsend", "townsend et al.", ". the u1", "u1 snrnp is", "snrnp is replaced", "is replaced at", "replaced at the", "at the 5'", "splice site by", "site by the", "u6 snrna and", "snrna and the", "and the spliceosome", "spliceosome is remodelled", "is remodelled to", "remodelled to yield", "the spliceosomal b", "spliceosomal b complex", "complex isma\u00efli", "isma\u00efli et al.", "et al. 2001", "2001 deckert", "deckert et al.", "et al. 2006", "2006 bessonov", "bessonov et al.", "2008 wolf", "wolf et al.", "et al. 2009", "2009 bessonov", "et al. 2010", "2010 schmidt", "schmidt et al.", "2016 bertram", "bertram et al.", "2018 kastner", "al. 2019 .", "2019 . the", ". the spliceosomal", "b complex is", "complex is activated", "is activated to", "activated to form", "the spliceosomal bact", "spliceosomal bact complex", "bact complex by", "complex by dissociation", "by dissociation of", "dissociation of the", "of the u4", "the u4 snrnp", "u4 snrnp and", "snrnp and lsm", "and lsm proteins", "lsm proteins from", "proteins from the", "from the u6", "snrna freeing", "freeing the u6", "u6 snrna to", "snrna to form", "form the active", "the active site", "active site of", "spliceosome lamond", "lamond et al.", "et al. 1988", "1988 laggerbauer", "laggerbauer et al.", "1998 ajuh", "ajuh et al.", "2000 bessonov", "2010 agafonov", "agafonov et al.", "et al. 2011", "2011 haselbach", "haselbach et al.", "2018 zhang", "2019 busetto", "busetto et al.", "2020 . dissociation", ". dissociation of", "of the sf3a", "the sf3a and", "sf3a and sf3b", "and sf3b subcomplexes", "sf3b subcomplexes of", "subcomplexes of the", "of the u2", "u2 snrnp allows", "snrnp allows the", "allows the intron", "the intron branch", "intron branch point", "branch point to", "point to dock", "to dock near", "dock near the", "near the 5'", "site forming", "forming the b*", "the b* spliceosomal", "b* spliceosomal complex.", "spliceosomal complex. reaction", "complex. reaction of", "reaction of the", "of the branch", "branch point at", "point at the", "yields the spliceosomal", "the spliceosomal c", "spliceosomal c complex", "complex jurica", "jurica et al.", "2002 makarov", "2002 reichert", "reichert et al.", "2002 kataoka", "2004 bessonov", "2010 gencheva", "gencheva et al.", "2011 alexandrov", "alexandrov et al.", "2012 barbosa", "barbosa et al.", "2012 steckelberg", "steckelberg et al.", "2012 schmidt", "2014 zhan", ". the branch", "branch point is", "point is rotated", "is rotated to", "rotated to allow", "to allow the", "allow the 3'", "splice site to", "site to enter", "to enter the", "enter the active", "site yielding", "yielding the spliceosomal", "the spliceosomal c*", "spliceosomal c* complex", "complex ortlepp", "ortlepp et al.", "1998 zhou", "zhou and reed", "and reed 1998", "1998 jurica", "2002 ilagan", "ilagan et al.", "2013 bertram", "2017 kastner", "2019 . reaction", ". reaction of", "of the 3'", "upstream exon at", "exon at the", "at the 3'", "splice site yields", "site yields the", "the spliceosomal p", "p postcatalytic", "postcatalytic complex", "complex zhou", "zhou et al.", "2000 kataoka", "2004 tange", "tange et al.", "et al. 2005", "2005 zhang", "zhang and krainer", "and krainer 2007", "2007 chi", "2013 ilagan", "2017 fica", "2019 zhang", "spliceosomal p complex", "p complex then", "complex then dissociates", "then dissociates to", "dissociates to yield", "to yield an", "yield an mrnp", "an mrnp containing", "mrnp containing the", "containing the spliced", "the spliced mrna", "spliced mrna and", "mrna and associated", "and associated proteins", "proteins including", "including the exon", "the exon junction", "exon junction complex", "complex ejc", "ohno and shimura", "and shimura 1996", "1996 merz", "merz et al.", "2007 yoshimoto", "yoshimoto et al.", "2009 zanini", "zanini et al.", "2017 felisberto", "felisberto rodrigues et", "rodrigues et al.", "2019 ejc", "ejc reviewed in", "reviewed in schlautmann", "in schlautmann and", "schlautmann and gehring", "and gehring 2020", "and the intron", "the intron lariat", "intron lariat spliceosome", "spliceosome ils", "which contains the", "contains the intron", "the intron lariat.", "intron lariat. the", "lariat. the ils", "the ils is", "ils is then", "is then disassembled", "then disassembled to", "disassembled to free", "to free its", "free its components", "its components for", "components for further", "for further splicing", "further splicing reactions", "splicing reactions and", "reactions and the", "intron lariat is", "lariat is degraded", "degraded wen", "wen et al.", "2008 yoshimoto", "2009 yoshimoto", "2014 zhang", "2019 studer", "studer et al.", "eukaryotic genes are transcribed", "genes are transcribed to", "are transcribed to yield", "transcribed to yield pre", "to yield pre mrnas", "yield pre mrnas that", "pre mrnas that are", "mrnas that are processed", "that are processed to", "are processed to add", "processed to add methyl", "to add methyl guanosine", "add methyl guanosine cap", "methyl guanosine cap structures", "guanosine cap structures and", "cap structures and polyadenylate", "structures and polyadenylate tails", "and polyadenylate tails and", "polyadenylate tails and to", "tails and to splice", "and to splice together", "to splice together segments", "splice together segments of", "together segments of a", "segments of a pre", "of a pre mrna", "a pre mrna termed", "pre mrna termed exons", "termed exons thereby", "exons thereby removing", "thereby removing segments termed", "removing segments termed introns.", "segments termed introns. more", "termed introns. more than", "introns. more than 90%", "more than 90% of", "than 90% of human", "90% of human genes", "of human genes contain", "human genes contain introns", "contain introns with", "introns with an", "with an average of", "an average of 4.0", "average of 4.0 introns", "of 4.0 introns per", "4.0 introns per gene", "introns per gene and", "per gene and 3413", "gene and 3413 nucleotides", "and 3413 nucleotides per", "3413 nucleotides per intron", "nucleotides per intron compared", "per intron compared with", "intron compared with 5.0", "compared with 5.0 exons", "with 5.0 exons per", "5.0 exons per gene", "exons per gene and", "per gene and 50.9", "gene and 50.9 nucleotides", "and 50.9 nucleotides per", "50.9 nucleotides per exon", "per exon deutsch", "exon deutsch and", "deutsch and long 1999", "and long 1999 .", "1999 . notable", ". notable exceptions", "notable exceptions are the", "exceptions are the histone", "are the histone genes", "histone genes which", "genes which are", "are intronless.
pre", "intronless.
pre mrna", "
pre mrna splicing is", "mrna splicing is performed", "splicing is performed by", "is performed by a", "performed by a large", "by a large ribonucleoprotein", "a large ribonucleoprotein complex", "ribonucleoprotein complex the", "complex the spliceosome", "the spliceosome which", "spliceosome which contains", "which contains 5 small", "contains 5 small nuclear", "5 small nuclear rnas", "nuclear rnas snrnas", "snrnas and more", "and more than 150", "more than 150 proteins", "150 proteins reviewed", "proteins reviewed in", "reviewed in will and", "in will and luhrmann", "will and luhrmann 2011", "luhrmann 2011 kastner", "2011 kastner et", "kastner et al. 2019", "al. 2019 yan", "2019 yan et", "yan et al. 2019", "al. 2019 fica", "2019 fica et", "fica et al. 2020", "al. 2020 wan", "2020 wan et", "wan et al. 2020", "al. 2020 wilkinson", "2020 wilkinson et", "wilkinson et al. 2020", "et al. 2020 .", "al. 2020 . the", "2020 . the catalyst", ". the catalyst in", "the catalyst in the", "catalyst in the spliceosome", "in the spliceosome comprises", "the spliceosome comprises magnesium", "spliceosome comprises magnesium ions", "comprises magnesium ions coordinated", "magnesium ions coordinated by", "ions coordinated by the", "coordinated by the u6", "by the u6 snrna", "the u6 snrna that", "u6 snrna that catalyze", "snrna that catalyze transesterification", "that catalyze transesterification reactions", "catalyze transesterification reactions between", "transesterification reactions between hydroxyl", "reactions between hydroxyl groups", "between hydroxyl groups and", "hydroxyl groups and phosphate", "groups and phosphate groups", "and phosphate groups from", "phosphate groups from the", "groups from the pre", "from the pre mrna.", "the pre mrna. the", "pre mrna. the role", "mrna. the role of", "the role of the", "role of the u6", "of the u6 snrna", "the u6 snrna demonstrates", "u6 snrna demonstrates that", "snrna demonstrates that the", "demonstrates that the spliceosome", "that the spliceosome is", "the spliceosome is a", "spliceosome is a ribozyme", "is a ribozyme hints", "a ribozyme hints at", "ribozyme hints at the", "hints at the origin", "at the origin of", "the origin of the", "origin of the spliceosome", "of the spliceosome as", "the spliceosome as a", "spliceosome as a self", "as a self splicing", "a self splicing group", "self splicing group ii", "splicing group ii intron.", "group ii intron.
the", "ii intron.
the spliceosome", "intron.
the spliceosome is", "
the spliceosome is initially", "spliceosome is initially assembled", "is initially assembled cotranscriptionally", "initially assembled cotranscriptionally on", "assembled cotranscriptionally on the", "cotranscriptionally on the pre", "on the pre mrna", "the pre mrna as", "pre mrna as the", "mrna as the spliceosomal", "as the spliceosomal e", "spliceosomal e early", "early complex and", "complex and then remodelled", "and then remodelled sequentially", "then remodelled sequentially by", "remodelled sequentially by association", "sequentially by association and", "by association and dissociation", "association and dissociation of", "and dissociation of proteins", "dissociation of proteins and", "of proteins and snrnas", "proteins and snrnas to", "and snrnas to catalyze", "snrnas to catalyze of", "to catalyze of the", "catalyze of the two", "of the two reactions", "the two reactions of", "two reactions of splicing.", "reactions of splicing. first", "splicing. first a", "first a nucleophilic", "a nucleophilic attack by", "nucleophilic attack by the", "attack by the 2'", "by the 2' hydroxyl", "the 2' hydroxyl group", "2' hydroxyl group of", "hydroxyl group of a", "group of a conserved", "of a conserved adenine", "a conserved adenine residue", "adenine residue the", "residue the branch", "branch point within", "point within the", "within the intron on", "the intron on the", "intron on the phosphate", "on the phosphate group", "the phosphate group of", "phosphate group of the", "group of the 5'", "of the 5' residue", "the 5' residue of", "5' residue of the", "residue of the intron", "of the intron yields", "the intron yields a", "intron yields a lariat", "a lariat looped", "looped structure in", "structure in the intron", "in the intron joined", "the intron joined to", "intron joined to the", "joined to the downstream", "the downstream 3'", "3' exon and", "exon and a free", "and a free upstream", "a free upstream exon", "free upstream exon with", "upstream exon with a", "exon with a 3'", "with a 3' hydroxyl", "a 3' hydroxyl group.", "3' hydroxyl group. second", "group. second a", "second a nucleophilic", "attack by the 3'", "by the 3' hydroxyl", "the 3' hydroxyl group", "3' hydroxyl group of", "hydroxyl group of the", "group of the upstream", "of the upstream exon", "the upstream exon on", "upstream exon on the", "exon on the phosphate", "on the phosphate of", "the phosphate of the", "phosphate of the 5'", "residue of the downstream", "of the downstream exon", "the downstream exon yields", "downstream exon yields a", "exon yields a spliced", "yields a spliced mrna", "a spliced mrna containing", "spliced mrna containing the", "mrna containing the upstream", "containing the upstream exon", "the upstream exon ligated", "upstream exon ligated to", "exon ligated to the", "ligated to the downstream", "to the downstream exon", "the downstream exon and", "downstream exon and a", "and a free intron", "a free intron containing", "free intron containing a", "intron containing a lariat", "containing a lariat structure.", "a lariat structure.
the", "lariat structure.
the spliceosomal", "structure.
the spliceosomal e", "
the spliceosomal e complex", "spliceosomal e complex contains", "e complex contains the", "complex contains the u1", "contains the u1 snrnp", "the u1 snrnp bound", "u1 snrnp bound to", "snrnp bound to the", "bound to the 5'", "to the 5' splice", "the 5' splice site", "splice site sf1", "site sf1 bound", "sf1 bound to the", "bound to the branch", "to the branch point", "branch point and", "point and the", "and the u2af complex", "the u2af complex bound", "u2af complex bound to", "complex bound to the", "bound to the polypyrimidine", "to the polypyrimidine tract", "the polypyrimidine tract of", "polypyrimidine tract of the", "tract of the intron", "of the intron and", "the intron and the", "intron and the 3'", "and the 3' splice", "the 3' splice site", "3' splice site of", "splice site of the", "site of the pre", "of the pre mrna", "pre mrna zhuang", "mrna zhuang and", "zhuang and weiner 1986", "weiner 1986 hong", "1986 hong et", "hong et al. 1997", "al. 1997 das", "1997 das et", "das et al. 2000", "al. 2000 hartmuth", "2000 hartmuth et", "hartmuth et al. 2002", "al. 2002 rappsilber", "2002 rappsilber et", "rappsilber et al. 2002", "al. 2002 hegele", "2002 hegele et", "hegele et al. 2012", "al. 2012 makarov", "2012 makarov et", "makarov et al. 2012", "al. 2012 crisci", "2012 crisci et", "crisci et al. 2015", "al. 2015 kondo", "2015 kondo et", "kondo et al. 2015", "al. 2015 tan", "2015 tan et", "tan et al. 2016", "et al. 2016 .", "al. 2016 . sf1", "2016 . sf1 and", ". sf1 and u2af", "sf1 and u2af are", "and u2af are displaced", "u2af are displaced on", "are displaced on the", "displaced on the pre", "the pre mrna and", "pre mrna and the", "mrna and the u2", "and the u2 snrnp", "the u2 snrnp binds", "u2 snrnp binds the", "snrnp binds the branch", "binds the branch region", "the branch region to", "branch region to yield", "region to yield the", "to yield the spliceosomal", "yield the spliceosomal a", "the spliceosomal a complex", "a complex wu", "complex wu and", "wu and manley 1989", "manley 1989 fleckner", "1989 fleckner et", "fleckner et al. 1997", "al. 1997 neubauer", "1997 neubauer et", "neubauer et al. 1998", "al. 1998 hartmuth", "1998 hartmuth et", "al. 2002 xu", "2002 xu et", "xu et al. 2004", "al. 2004 behzadnia", "2004 behzadnia et", "behzadnia et al. 2007", "al. 2007 shen", "2007 shen et", "shen et al. 2008", "al. 2008 chen", "2008 chen et", "chen et al. 2017", "al. 2017 zhang", "2017 zhang et", "zhang et al. 2020", "2020 . the u4/u6.u5", ". the u4/u6.u5 tri", "the u4/u6.u5 tri snrnp", "tri snrnp containing", "snrnp containing the", "containing the u4 snrna", "the u4 snrna base", "u4 snrna base paired", "snrna base paired with", "base paired with the", "paired with the u6", "with the u6 snrna", "the u6 snrna plus", "u6 snrna plus the", "snrna plus the u5", "plus the u5 snrnp", "the u5 snrnp and", "u5 snrnp and accessory", "snrnp and accessory proteins", "accessory proteins binds", "proteins binds the", "binds the spliceosomal a", "spliceosomal a complex to", "a complex to form", "complex to form the", "to form the spliceosomal", "form the spliceosomal pre", "the spliceosomal pre b", "spliceosomal pre b complex", "b complex hausner", "complex hausner et", "hausner et al. 1990", "al. 1990 kataoka", "1990 kataoka and", "kataoka and dreyfuss 2004", "dreyfuss 2004 chi", "2004 chi et", "chi et al. 2013", "al. 2013 mohlmann", "2013 mohlmann et", "mohlmann et al. 2014", "al. 2014 boesler", "2014 boesler et", "boesler et al. 2016", "al. 2016 zhan", "2016 zhan et", "zhan et al. 2018", "al. 2018 charenton", "2018 charenton et", "charenton et al. 2019", "al. 2019 kastner", "2019 kastner et", "al. 2019 townsend", "2019 townsend et", "townsend et al. 2020", "2020 . the u1", ". the u1 snrnp", "the u1 snrnp is", "u1 snrnp is replaced", "snrnp is replaced at", "is replaced at the", "replaced at the 5'", "at the 5' splice", "5' splice site by", "splice site by the", "site by the u6", "the u6 snrna and", "u6 snrna and the", "snrna and the spliceosome", "and the spliceosome is", "the spliceosome is remodelled", "spliceosome is remodelled to", "is remodelled to yield", "remodelled to yield the", "yield the spliceosomal b", "the spliceosomal b complex", "b complex isma\u00efli", "complex isma\u00efli et", "isma\u00efli et al. 2001", "al. 2001 deckert", "2001 deckert et", "deckert et al. 2006", "al. 2006 bessonov", "2006 bessonov et", "bessonov et al. 2008", "al. 2008 wolf", "2008 wolf et", "wolf et al. 2009", "al. 2009 bessonov", "2009 bessonov et", "bessonov et al. 2010", "al. 2010 schmidt", "2010 schmidt et", "schmidt et al. 2014", "al. 2016 bertram", "2016 bertram et", "bertram et al. 2017", "zhang et al. 2018", "al. 2018 kastner", "2018 kastner et", "et al. 2019 .", "al. 2019 . the", "2019 . the spliceosomal", ". the spliceosomal b", "spliceosomal b complex is", "b complex is activated", "complex is activated to", "is activated to form", "activated to form the", "form the spliceosomal bact", "the spliceosomal bact complex", "spliceosomal bact complex by", "bact complex by dissociation", "complex by dissociation of", "by dissociation of the", "dissociation of the u4", "of the u4 snrnp", "the u4 snrnp and", "u4 snrnp and lsm", "snrnp and lsm proteins", "and lsm proteins from", "lsm proteins from the", "proteins from the u6", "from the u6 snrna", "u6 snrna freeing", "snrna freeing the", "freeing the u6 snrna", "the u6 snrna to", "u6 snrna to form", "snrna to form the", "to form the active", "form the active site", "the active site of", "active site of the", "site of the spliceosome", "the spliceosome lamond", "spliceosome lamond et", "lamond et al. 1988", "al. 1988 laggerbauer", "1988 laggerbauer et", "laggerbauer et al. 1998", "al. 1998 ajuh", "1998 ajuh et", "ajuh et al. 2000", "al. 2000 bessonov", "2000 bessonov et", "al. 2010 agafonov", "2010 agafonov et", "agafonov et al. 2011", "al. 2011 haselbach", "2011 haselbach et", "haselbach et al. 2018", "al. 2018 zhang", "2018 zhang et", "al. 2019 busetto", "2019 busetto et", "busetto et al. 2020", "al. 2020 . dissociation", "2020 . dissociation of", ". dissociation of the", "dissociation of the sf3a", "of the sf3a and", "the sf3a and sf3b", "sf3a and sf3b subcomplexes", "and sf3b subcomplexes of", "sf3b subcomplexes of the", "subcomplexes of the u2", "of the u2 snrnp", "the u2 snrnp allows", "u2 snrnp allows the", "snrnp allows the intron", "allows the intron branch", "the intron branch point", "intron branch point to", "branch point to dock", "point to dock near", "to dock near the", "dock near the 5'", "near the 5' splice", "splice site forming", "site forming the", "forming the b* spliceosomal", "the b* spliceosomal complex.", "b* spliceosomal complex. reaction", "spliceosomal complex. reaction of", "complex. reaction of the", "reaction of the branch", "of the branch point", "the branch point at", "branch point at the", "point at the 5'", "yields the spliceosomal c", "the spliceosomal c complex", "c complex jurica", "complex jurica et", "jurica et al. 2002", "al. 2002 makarov", "2002 makarov et", "makarov et al. 2002", "al. 2002 reichert", "2002 reichert et", "reichert et al. 2002", "al. 2002 kataoka", "2002 kataoka and", "dreyfuss 2004 bessonov", "2004 bessonov et", "al. 2010 gencheva", "2010 gencheva et", "gencheva et al. 2010", "al. 2011 alexandrov", "2011 alexandrov et", "alexandrov et al. 2012", "al. 2012 barbosa", "2012 barbosa et", "barbosa et al. 2012", "al. 2012 steckelberg", "2012 steckelberg et", "steckelberg et al. 2012", "al. 2012 schmidt", "2012 schmidt et", "al. 2014 zhan", "2014 zhan et", "2020 . the branch", ". the branch point", "the branch point is", "branch point is rotated", "point is rotated to", "is rotated to allow", "rotated to allow the", "to allow the 3'", "allow the 3' splice", "3' splice site to", "splice site to enter", "site to enter the", "to enter the active", "enter the active site", "active site yielding", "site yielding the", "yielding the spliceosomal c*", "the spliceosomal c* complex", "c* complex ortlepp", "complex ortlepp et", "ortlepp et al. 1998", "al. 1998 zhou", "1998 zhou and", "zhou and reed 1998", "reed 1998 jurica", "1998 jurica et", "al. 2002 ilagan", "2002 ilagan et", "ilagan et al. 2013", "al. 2013 bertram", "2013 bertram et", "zhang et al. 2017", "al. 2017 kastner", "2017 kastner et", "al. 2019 . reaction", "2019 . reaction of", ". reaction of the", "reaction of the 3'", "of the 3' hydroxyl", "the upstream exon at", "upstream exon at the", "exon at the 3'", "at the 3' splice", "3' splice site yields", "splice site yields the", "site yields the spliceosomal", "yields the spliceosomal p", "spliceosomal p postcatalytic", "complex zhou et", "zhou et al. 2000", "al. 2000 kataoka", "2000 kataoka and", "dreyfuss 2004 tange", "2004 tange et", "tange et al. 2005", "al. 2005 zhang", "2005 zhang and", "zhang and krainer 2007", "krainer 2007 chi", "2007 chi et", "al. 2013 ilagan", "2013 ilagan et", "al. 2017 fica", "2017 fica et", "fica et al. 2019", "al. 2019 zhang", "2019 zhang et", "zhang et al. 2019", ". the spliceosomal p", "the spliceosomal p complex", "spliceosomal p complex then", "p complex then dissociates", "complex then dissociates to", "then dissociates to yield", "dissociates to yield an", "to yield an mrnp", "yield an mrnp containing", "an mrnp containing the", "mrnp containing the spliced", "containing the spliced mrna", "the spliced mrna and", "spliced mrna and associated", "mrna and associated proteins", "associated proteins including", "proteins including the", "including the exon junction", "the exon junction complex", "junction complex ejc", "ejc ohno", "ohno and shimura 1996", "shimura 1996 merz", "1996 merz et", "merz et al. 2007", "al. 2007 yoshimoto", "2007 yoshimoto et", "yoshimoto et al. 2009", "al. 2009 zanini", "2009 zanini et", "zanini et al. 2017", "al. 2017 felisberto", "2017 felisberto rodrigues", "felisberto rodrigues et al.", "rodrigues et al. 2019", "al. 2019 ejc", "2019 ejc reviewed", "ejc reviewed in schlautmann", "reviewed in schlautmann and", "in schlautmann and gehring", "schlautmann and gehring 2020", "2020 and", "and the intron lariat", "the intron lariat spliceosome", "lariat spliceosome ils", "ils which", "which contains the intron", "contains the intron lariat.", "the intron lariat. the", "intron lariat. the ils", "lariat. the ils is", "the ils is then", "ils is then disassembled", "is then disassembled to", "then disassembled to free", "disassembled to free its", "to free its components", "free its components for", "its components for further", "components for further splicing", "for further splicing reactions", "further splicing reactions and", "splicing reactions and the", "reactions and the intron", "the intron lariat is", "intron lariat is degraded", "is degraded wen", "degraded wen et", "wen et al. 2008", "al. 2008 yoshimoto", "2008 yoshimoto et", "al. 2009 yoshimoto", "2009 yoshimoto et", "yoshimoto et al. 2014", "al. 2014 zhang", "2014 zhang et", "al. 2019 studer", "2019 studer et", "studer et al. 2020", "eukaryotic genes are transcribed to", "genes are transcribed to yield", "are transcribed to yield pre", "transcribed to yield pre mrnas", "to yield pre mrnas that", "yield pre mrnas that are", "pre mrnas that are processed", "mrnas that are processed to", "that are processed to add", "are processed to add methyl", "processed to add methyl guanosine", "to add methyl guanosine cap", "add methyl guanosine cap structures", "methyl guanosine cap structures and", "guanosine cap structures and polyadenylate", "cap structures and polyadenylate tails", "structures and polyadenylate tails and", "and polyadenylate tails and to", "polyadenylate tails and to splice", "tails and to splice together", "and to splice together segments", "to splice together segments of", "splice together segments of a", "together segments of a pre", "segments of a pre mrna", "of a pre mrna termed", "a pre mrna termed exons", "mrna termed exons thereby", "termed exons thereby removing", "exons thereby removing segments", "thereby removing segments termed introns.", "removing segments termed introns. more", "segments termed introns. more than", "termed introns. more than 90%", "introns. more than 90% of", "more than 90% of human", "than 90% of human genes", "90% of human genes contain", "of human genes contain introns", "genes contain introns with", "contain introns with an", "introns with an average", "with an average of 4.0", "an average of 4.0 introns", "average of 4.0 introns per", "of 4.0 introns per gene", "4.0 introns per gene and", "introns per gene and 3413", "per gene and 3413 nucleotides", "gene and 3413 nucleotides per", "and 3413 nucleotides per intron", "3413 nucleotides per intron compared", "nucleotides per intron compared with", "per intron compared with 5.0", "intron compared with 5.0 exons", "compared with 5.0 exons per", "with 5.0 exons per gene", "5.0 exons per gene and", "exons per gene and 50.9", "per gene and 50.9 nucleotides", "gene and 50.9 nucleotides per", "and 50.9 nucleotides per exon", "nucleotides per exon deutsch", "per exon deutsch and", "exon deutsch and long", "deutsch and long 1999 .", "long 1999 . notable", "1999 . notable exceptions", ". notable exceptions are", "notable exceptions are the histone", "exceptions are the histone genes", "the histone genes which", "histone genes which are", "genes which are intronless.", "which are intronless.
pre", "are intronless.
pre mrna", "intronless.
pre mrna splicing", "
pre mrna splicing is performed", "mrna splicing is performed by", "splicing is performed by a", "is performed by a large", "performed by a large ribonucleoprotein", "by a large ribonucleoprotein complex", "large ribonucleoprotein complex the", "ribonucleoprotein complex the spliceosome", "the spliceosome which contains", "spliceosome which contains 5", "which contains 5 small nuclear", "contains 5 small nuclear rnas", "small nuclear rnas snrnas", "rnas snrnas and", "snrnas and more than", "and more than 150 proteins", "than 150 proteins reviewed", "150 proteins reviewed in", "proteins reviewed in will", "reviewed in will and luhrmann", "in will and luhrmann 2011", "and luhrmann 2011 kastner", "luhrmann 2011 kastner et", "2011 kastner et al.", "et al. 2019 yan", "al. 2019 yan et", "2019 yan et al.", "et al. 2019 fica", "al. 2019 fica et", "2019 fica et al.", "et al. 2020 wan", "al. 2020 wan et", "2020 wan et al.", "et al. 2020 wilkinson", "al. 2020 wilkinson et", "2020 wilkinson et al.", "wilkinson et al. 2020 .", "et al. 2020 . the", "al. 2020 . the catalyst", "2020 . the catalyst in", ". the catalyst in the", "the catalyst in the spliceosome", "catalyst in the spliceosome comprises", "in the spliceosome comprises magnesium", "the spliceosome comprises magnesium ions", "spliceosome comprises magnesium ions coordinated", "comprises magnesium ions coordinated by", "magnesium ions coordinated by the", "ions coordinated by the u6", "coordinated by the u6 snrna", "by the u6 snrna that", "the u6 snrna that catalyze", "u6 snrna that catalyze transesterification", "snrna that catalyze transesterification reactions", "that catalyze transesterification reactions between", "catalyze transesterification reactions between hydroxyl", "transesterification reactions between hydroxyl groups", "reactions between hydroxyl groups and", "between hydroxyl groups and phosphate", "hydroxyl groups and phosphate groups", "groups and phosphate groups from", "and phosphate groups from the", "phosphate groups from the pre", "groups from the pre mrna.", "from the pre mrna. the", "the pre mrna. the role", "pre mrna. the role of", "mrna. the role of the", "the role of the u6", "role of the u6 snrna", "of the u6 snrna demonstrates", "the u6 snrna demonstrates that", "u6 snrna demonstrates that the", "snrna demonstrates that the spliceosome", "demonstrates that the spliceosome is", "that the spliceosome is a", "the spliceosome is a ribozyme", "spliceosome is a ribozyme hints", "is a ribozyme hints at", "a ribozyme hints at the", "ribozyme hints at the origin", "hints at the origin of", "at the origin of the", "the origin of the spliceosome", "origin of the spliceosome as", "of the spliceosome as a", "the spliceosome as a self", "spliceosome as a self splicing", "as a self splicing group", "a self splicing group ii", "self splicing group ii intron.", "splicing group ii intron.
the", "group ii intron.
the spliceosome", "ii intron.
the spliceosome is", "intron.
the spliceosome is initially", "
the spliceosome is initially assembled", "spliceosome is initially assembled cotranscriptionally", "is initially assembled cotranscriptionally on", "initially assembled cotranscriptionally on the", "assembled cotranscriptionally on the pre", "cotranscriptionally on the pre mrna", "on the pre mrna as", "the pre mrna as the", "pre mrna as the spliceosomal", "mrna as the spliceosomal e", "the spliceosomal e early", "e early complex", "early complex and then", "complex and then remodelled sequentially", "and then remodelled sequentially by", "then remodelled sequentially by association", "remodelled sequentially by association and", "sequentially by association and dissociation", "by association and dissociation of", "association and dissociation of proteins", "and dissociation of proteins and", "dissociation of proteins and snrnas", "of proteins and snrnas to", "proteins and snrnas to catalyze", "and snrnas to catalyze of", "snrnas to catalyze of the", "to catalyze of the two", "catalyze of the two reactions", "of the two reactions of", "the two reactions of splicing.", "two reactions of splicing. first", "of splicing. first a", "splicing. first a nucleophilic", "first a nucleophilic attack", "a nucleophilic attack by the", "nucleophilic attack by the 2'", "attack by the 2' hydroxyl", "by the 2' hydroxyl group", "the 2' hydroxyl group of", "2' hydroxyl group of a", "hydroxyl group of a conserved", "group of a conserved adenine", "of a conserved adenine residue", "conserved adenine residue the", "adenine residue the branch", "residue the branch point", "the branch point within", "branch point within the", "point within the intron", "within the intron on the", "the intron on the phosphate", "intron on the phosphate group", "on the phosphate group of", "the phosphate group of the", "phosphate group of the 5'", "group of the 5' residue", "of the 5' residue of", "the 5' residue of the", "5' residue of the intron", "residue of the intron yields", "of the intron yields a", "the intron yields a lariat", "yields a lariat looped", "lariat looped structure", "looped structure in the", "structure in the intron joined", "in the intron joined to", "the intron joined to the", "intron joined to the downstream", "to the downstream 3'", "downstream 3' exon", "3' exon and a", "exon and a free upstream", "and a free upstream exon", "a free upstream exon with", "free upstream exon with a", "upstream exon with a 3'", "exon with a 3' hydroxyl", "with a 3' hydroxyl group.", "a 3' hydroxyl group. second", "hydroxyl group. second a", "group. second a nucleophilic", "second a nucleophilic attack", "nucleophilic attack by the 3'", "attack by the 3' hydroxyl", "by the 3' hydroxyl group", "the 3' hydroxyl group of", "3' hydroxyl group of the", "hydroxyl group of the upstream", "group of the upstream exon", "of the upstream exon on", "the upstream exon on the", "upstream exon on the phosphate", "exon on the phosphate of", "on the phosphate of the", "the phosphate of the 5'", "phosphate of the 5' residue", "5' residue of the downstream", "residue of the downstream exon", "of the downstream exon yields", "the downstream exon yields a", "downstream exon yields a spliced", "exon yields a spliced mrna", "yields a spliced mrna containing", "a spliced mrna containing the", "spliced mrna containing the upstream", "mrna containing the upstream exon", "containing the upstream exon ligated", "the upstream exon ligated to", "upstream exon ligated to the", "exon ligated to the downstream", "ligated to the downstream exon", "to the downstream exon and", "the downstream exon and a", "downstream exon and a free", "exon and a free intron", "and a free intron containing", "a free intron containing a", "free intron containing a lariat", "intron containing a lariat structure.", "containing a lariat structure.
the", "a lariat structure.
the spliceosomal", "lariat structure.
the spliceosomal e", "structure.
the spliceosomal e complex", "
the spliceosomal e complex contains", "spliceosomal e complex contains the", "e complex contains the u1", "complex contains the u1 snrnp", "contains the u1 snrnp bound", "the u1 snrnp bound to", "u1 snrnp bound to the", "snrnp bound to the 5'", "bound to the 5' splice", "to the 5' splice site", "5' splice site sf1", "splice site sf1 bound", "site sf1 bound to", "sf1 bound to the branch", "bound to the branch point", "the branch point and", "branch point and the", "point and the u2af", "and the u2af complex bound", "the u2af complex bound to", "u2af complex bound to the", "complex bound to the polypyrimidine", "bound to the polypyrimidine tract", "to the polypyrimidine tract of", "the polypyrimidine tract of the", "polypyrimidine tract of the intron", "tract of the intron and", "of the intron and the", "the intron and the 3'", "intron and the 3' splice", "and the 3' splice site", "the 3' splice site of", "3' splice site of the", "splice site of the pre", "site of the pre mrna", "the pre mrna zhuang", "pre mrna zhuang and", "mrna zhuang and weiner", "and weiner 1986 hong", "weiner 1986 hong et", "1986 hong et al.", "et al. 1997 das", "al. 1997 das et", "1997 das et al.", "et al. 2000 hartmuth", "al. 2000 hartmuth et", "2000 hartmuth et al.", "et al. 2002 rappsilber", "al. 2002 rappsilber et", "2002 rappsilber et al.", "et al. 2002 hegele", "al. 2002 hegele et", "2002 hegele et al.", "et al. 2012 makarov", "al. 2012 makarov et", "2012 makarov et al.", "et al. 2012 crisci", "al. 2012 crisci et", "2012 crisci et al.", "et al. 2015 kondo", "al. 2015 kondo et", "2015 kondo et al.", "et al. 2015 tan", "al. 2015 tan et", "2015 tan et al.", "tan et al. 2016 .", "et al. 2016 . sf1", "al. 2016 . sf1 and", "2016 . sf1 and u2af", ". sf1 and u2af are", "sf1 and u2af are displaced", "and u2af are displaced on", "u2af are displaced on the", "are displaced on the pre", "displaced on the pre mrna", "on the pre mrna and", "the pre mrna and the", "pre mrna and the u2", "mrna and the u2 snrnp", "and the u2 snrnp binds", "the u2 snrnp binds the", "u2 snrnp binds the branch", "snrnp binds the branch region", "binds the branch region to", "the branch region to yield", "branch region to yield the", "region to yield the spliceosomal", "to yield the spliceosomal a", "yield the spliceosomal a complex", "spliceosomal a complex wu", "a complex wu and", "complex wu and manley", "and manley 1989 fleckner", "manley 1989 fleckner et", "1989 fleckner et al.", "et al. 1997 neubauer", "al. 1997 neubauer et", "1997 neubauer et al.", "et al. 1998 hartmuth", "al. 1998 hartmuth et", "1998 hartmuth et al.", "et al. 2002 xu", "al. 2002 xu et", "2002 xu et al.", "et al. 2004 behzadnia", "al. 2004 behzadnia et", "2004 behzadnia et al.", "et al. 2007 shen", "al. 2007 shen et", "2007 shen et al.", "et al. 2008 chen", "al. 2008 chen et", "2008 chen et al.", "et al. 2017 zhang", "al. 2017 zhang et", "2017 zhang et al.", "zhang et al. 2020 .", "al. 2020 . the u4/u6.u5", "2020 . the u4/u6.u5 tri", ". the u4/u6.u5 tri snrnp", "u4/u6.u5 tri snrnp containing", "tri snrnp containing the", "snrnp containing the u4", "containing the u4 snrna base", "the u4 snrna base paired", "u4 snrna base paired with", "snrna base paired with the", "base paired with the u6", "paired with the u6 snrna", "with the u6 snrna plus", "the u6 snrna plus the", "u6 snrna plus the u5", "snrna plus the u5 snrnp", "plus the u5 snrnp and", "the u5 snrnp and accessory", "u5 snrnp and accessory proteins", "and accessory proteins binds", "accessory proteins binds the", "proteins binds the spliceosomal", "binds the spliceosomal a complex", "the spliceosomal a complex to", "spliceosomal a complex to form", "a complex to form the", "complex to form the spliceosomal", "to form the spliceosomal pre", "form the spliceosomal pre b", "the spliceosomal pre b complex", "pre b complex hausner", "b complex hausner et", "complex hausner et al.", "et al. 1990 kataoka", "al. 1990 kataoka and", "1990 kataoka and dreyfuss", "and dreyfuss 2004 chi", "dreyfuss 2004 chi et", "2004 chi et al.", "et al. 2013 mohlmann", "al. 2013 mohlmann et", "2013 mohlmann et al.", "et al. 2014 boesler", "al. 2014 boesler et", "2014 boesler et al.", "et al. 2016 zhan", "al. 2016 zhan et", "2016 zhan et al.", "et al. 2018 charenton", "al. 2018 charenton et", "2018 charenton et al.", "et al. 2019 kastner", "al. 2019 kastner et", "2019 kastner et al.", "et al. 2019 townsend", "al. 2019 townsend et", "2019 townsend et al.", "townsend et al. 2020 .", "al. 2020 . the u1", "2020 . the u1 snrnp", ". the u1 snrnp is", "the u1 snrnp is replaced", "u1 snrnp is replaced at", "snrnp is replaced at the", "is replaced at the 5'", "replaced at the 5' splice", "at the 5' splice site", "the 5' splice site by", "5' splice site by the", "splice site by the u6", "site by the u6 snrna", "by the u6 snrna and", "the u6 snrna and the", "u6 snrna and the spliceosome", "snrna and the spliceosome is", "and the spliceosome is remodelled", "the spliceosome is remodelled to", "spliceosome is remodelled to yield", "is remodelled to yield the", "remodelled to yield the spliceosomal", "to yield the spliceosomal b", "yield the spliceosomal b complex", "spliceosomal b complex isma\u00efli", "b complex isma\u00efli et", "complex isma\u00efli et al.", "et al. 2001 deckert", "al. 2001 deckert et", "2001 deckert et al.", "et al. 2006 bessonov", "al. 2006 bessonov et", "2006 bessonov et al.", "et al. 2008 wolf", "al. 2008 wolf et", "2008 wolf et al.", "et al. 2009 bessonov", "al. 2009 bessonov et", "2009 bessonov et al.", "et al. 2010 schmidt", "al. 2010 schmidt et", "2010 schmidt et al.", "et al. 2016 bertram", "al. 2016 bertram et", "2016 bertram et al.", "et al. 2018 kastner", "al. 2018 kastner et", "2018 kastner et al.", "kastner et al. 2019 .", "et al. 2019 . the", "al. 2019 . the spliceosomal", "2019 . the spliceosomal b", ". the spliceosomal b complex", "the spliceosomal b complex is", "spliceosomal b complex is activated", "b complex is activated to", "complex is activated to form", "is activated to form the", "activated to form the spliceosomal", "to form the spliceosomal bact", "form the spliceosomal bact complex", "the spliceosomal bact complex by", "spliceosomal bact complex by dissociation", "bact complex by dissociation of", "complex by dissociation of the", "by dissociation of the u4", "dissociation of the u4 snrnp", "of the u4 snrnp and", "the u4 snrnp and lsm", "u4 snrnp and lsm proteins", "snrnp and lsm proteins from", "and lsm proteins from the", "lsm proteins from the u6", "proteins from the u6 snrna", "the u6 snrna freeing", "u6 snrna freeing the", "snrna freeing the u6", "freeing the u6 snrna to", "the u6 snrna to form", "u6 snrna to form the", "snrna to form the active", "to form the active site", "form the active site of", "the active site of the", "active site of the spliceosome", "of the spliceosome lamond", "the spliceosome lamond et", "spliceosome lamond et al.", "et al. 1988 laggerbauer", "al. 1988 laggerbauer et", "1988 laggerbauer et al.", "et al. 1998 ajuh", "al. 1998 ajuh et", "1998 ajuh et al.", "et al. 2000 bessonov", "al. 2000 bessonov et", "2000 bessonov et al.", "et al. 2010 agafonov", "al. 2010 agafonov et", "2010 agafonov et al.", "et al. 2011 haselbach", "al. 2011 haselbach et", "2011 haselbach et al.", "et al. 2018 zhang", "al. 2018 zhang et", "2018 zhang et al.", "et al. 2019 busetto", "al. 2019 busetto et", "2019 busetto et al.", "busetto et al. 2020 .", "et al. 2020 . dissociation", "al. 2020 . dissociation of", "2020 . dissociation of the", ". dissociation of the sf3a", "dissociation of the sf3a and", "of the sf3a and sf3b", "the sf3a and sf3b subcomplexes", "sf3a and sf3b subcomplexes of", "and sf3b subcomplexes of the", "sf3b subcomplexes of the u2", "subcomplexes of the u2 snrnp", "of the u2 snrnp allows", "the u2 snrnp allows the", "u2 snrnp allows the intron", "snrnp allows the intron branch", "allows the intron branch point", "the intron branch point to", "intron branch point to dock", "branch point to dock near", "point to dock near the", "to dock near the 5'", "dock near the 5' splice", "near the 5' splice site", "5' splice site forming", "splice site forming the", "site forming the b*", "forming the b* spliceosomal complex.", "the b* spliceosomal complex. reaction", "b* spliceosomal complex. reaction of", "spliceosomal complex. reaction of the", "complex. reaction of the branch", "reaction of the branch point", "of the branch point at", "the branch point at the", "branch point at the 5'", "point at the 5' splice", "5' splice site yields", "yields the spliceosomal c complex", "spliceosomal c complex jurica", "c complex jurica et", "complex jurica et al.", "et al. 2002 makarov", "al. 2002 makarov et", "2002 makarov et al.", "et al. 2002 reichert", "al. 2002 reichert et", "2002 reichert et al.", "et al. 2002 kataoka", "al. 2002 kataoka and", "2002 kataoka and dreyfuss", "and dreyfuss 2004 bessonov", "dreyfuss 2004 bessonov et", "2004 bessonov et al.", "et al. 2010 gencheva", "al. 2010 gencheva et", "2010 gencheva et al.", "et al. 2011 alexandrov", "al. 2011 alexandrov et", "2011 alexandrov et al.", "et al. 2012 barbosa", "al. 2012 barbosa et", "2012 barbosa et al.", "et al. 2012 steckelberg", "al. 2012 steckelberg et", "2012 steckelberg et al.", "et al. 2012 schmidt", "al. 2012 schmidt et", "2012 schmidt et al.", "et al. 2014 zhan", "al. 2014 zhan et", "2014 zhan et al.", "al. 2020 . the branch", "2020 . the branch point", ". the branch point is", "the branch point is rotated", "branch point is rotated to", "point is rotated to allow", "is rotated to allow the", "rotated to allow the 3'", "to allow the 3' splice", "allow the 3' splice site", "the 3' splice site to", "3' splice site to enter", "splice site to enter the", "site to enter the active", "to enter the active site", "the active site yielding", "active site yielding the", "site yielding the spliceosomal", "yielding the spliceosomal c* complex", "spliceosomal c* complex ortlepp", "c* complex ortlepp et", "complex ortlepp et al.", "et al. 1998 zhou", "al. 1998 zhou and", "1998 zhou and reed", "and reed 1998 jurica", "reed 1998 jurica et", "1998 jurica et al.", "et al. 2002 ilagan", "al. 2002 ilagan et", "2002 ilagan et al.", "et al. 2013 bertram", "al. 2013 bertram et", "2013 bertram et al.", "et al. 2017 kastner", "al. 2017 kastner et", "2017 kastner et al.", "et al. 2019 . reaction", "al. 2019 . reaction of", "2019 . reaction of the", ". reaction of the 3'", "reaction of the 3' hydroxyl", "of the 3' hydroxyl group", "of the upstream exon at", "the upstream exon at the", "upstream exon at the 3'", "exon at the 3' splice", "at the 3' splice site", "the 3' splice site yields", "3' splice site yields the", "splice site yields the spliceosomal", "site yields the spliceosomal p", "the spliceosomal p postcatalytic", "p postcatalytic complex", "postcatalytic complex zhou", "complex zhou et al.", "et al. 2000 kataoka", "al. 2000 kataoka and", "2000 kataoka and dreyfuss", "and dreyfuss 2004 tange", "dreyfuss 2004 tange et", "2004 tange et al.", "et al. 2005 zhang", "al. 2005 zhang and", "2005 zhang and krainer", "and krainer 2007 chi", "krainer 2007 chi et", "2007 chi et al.", "et al. 2013 ilagan", "al. 2013 ilagan et", "2013 ilagan et al.", "et al. 2017 fica", "al. 2017 fica et", "2017 fica et al.", "et al. 2019 zhang", "al. 2019 zhang et", "2019 zhang et al.", "zhang et al. 2019 .", "2019 . the spliceosomal p", ". the spliceosomal p complex", "the spliceosomal p complex then", "spliceosomal p complex then dissociates", "p complex then dissociates to", "complex then dissociates to yield", "then dissociates to yield an", "dissociates to yield an mrnp", "to yield an mrnp containing", "yield an mrnp containing the", "an mrnp containing the spliced", "mrnp containing the spliced mrna", "containing the spliced mrna and", "the spliced mrna and associated", "spliced mrna and associated proteins", "and associated proteins including", "associated proteins including the", "proteins including the exon", "including the exon junction complex", "exon junction complex ejc", "ejc ohno and", "and shimura 1996 merz", "shimura 1996 merz et", "1996 merz et al.", "et al. 2007 yoshimoto", "al. 2007 yoshimoto et", "2007 yoshimoto et al.", "et al. 2009 zanini", "al. 2009 zanini et", "2009 zanini et al.", "et al. 2017 felisberto", "al. 2017 felisberto rodrigues", "2017 felisberto rodrigues et", "felisberto rodrigues et al. 2019", "et al. 2019 ejc", "al. 2019 ejc reviewed", "2019 ejc reviewed in", "ejc reviewed in schlautmann and", "reviewed in schlautmann and gehring", "in schlautmann and gehring 2020", "gehring 2020 and", "2020 and the", "and the intron lariat spliceosome", "intron lariat spliceosome ils", "ils which contains", "which contains the intron lariat.", "contains the intron lariat. the", "the intron lariat. the ils", "intron lariat. the ils is", "lariat. the ils is then", "the ils is then disassembled", "ils is then disassembled to", "is then disassembled to free", "then disassembled to free its", "disassembled to free its components", "to free its components for", "free its components for further", "its components for further splicing", "components for further splicing reactions", "for further splicing reactions and", "further splicing reactions and the", "splicing reactions and the intron", "reactions and the intron lariat", "and the intron lariat is", "the intron lariat is degraded", "lariat is degraded wen", "is degraded wen et", "degraded wen et al.", "et al. 2008 yoshimoto", "al. 2008 yoshimoto et", "2008 yoshimoto et al.", "et al. 2009 yoshimoto", "al. 2009 yoshimoto et", "2009 yoshimoto et al.", "et al. 2014 zhang", "al. 2014 zhang et", "2014 zhang et al.", "et al. 2019 studer", "al. 2019 studer et", "2019 studer et al.", "studer et al. 2020 ." ] }, { "record_id": "GLY_000594_1_569", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72187", "r hsa", "hsa 72187", "r hsa 72187" ] }, { "record_id": "GLY_000594_1_569", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna 3'", "3' end", "end processing", "mrna 3' end", "3' end processing", "mrna 3' end processing", "the 3'", "3' ends", "ends of", "of eukaryotic", "eukaryotic mrnas", "mrnas are", "are generated", "generated by", "by posttranscriptional", "posttranscriptional processing", "processing of", "of an", "an extended", "extended primary", "primary transcript.", "transcript. for", "for almost", "almost all", "all rnas", "processing consists", "consists of", "of two", "two steps:", "the mrna", "mrna is", "is first", "first cleaved", "cleaved at", "at a", "a particular", "particular phosphodiester", "phosphodiester bond", "bond downstream", "downstream of", "of the", "the coding", "coding sequence", "the upstream", "upstream fragment", "fragment then", "then receives", "receives a", "a poly", "poly a", 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"id", "phraselist": [ "gly_000594", "hsa", "73614", "r hsa", "hsa 73614", "r hsa 73614" ] }, { "record_id": "GLY_000594_1_576", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pyrimidine salvage", "in pyrimidine", "salvage reactions", "nucleosides and", "and free", "free bases", "bases generated", "generated by", "by dna", "dna and", "and rna", "rna breakdown", "breakdown are", "are converted", "converted back", "back to", "to nucleotide", "nucleotide monophosphates", "allowing them", "them to", "to re", "re enter", "enter the", "the pathways", "pathways of", "of pyrimidine", "pyrimidine biosynthesis", "biosynthesis and", "and interconversion.", "in pyrimidine salvage", "pyrimidine salvage reactions", "reactions nucleosides", "nucleosides and free", "and free bases", "free bases generated", "bases generated by", "generated by dna", "by dna and", "dna and rna", "and rna breakdown", "rna breakdown are", "breakdown are converted", "are converted back", 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"phraselist": [ "gly_000594", "hsa", "73779", "r hsa", "hsa 73779", "r hsa 73779" ] }, { "record_id": "GLY_000594_1_580", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase ii", "ii transcription", "transcription pre", "pre initiation", "initiation and", "and promoter", "promoter opening", "rna polymerase ii", "polymerase ii transcription", "ii transcription pre", "transcription pre initiation", "pre initiation and", "initiation and promoter", "and promoter opening", "rna polymerase ii transcription", "polymerase ii transcription pre", "ii transcription pre initiation", "transcription pre initiation and", "pre initiation and promoter", "initiation and promoter opening", "rna polymerase ii transcription pre", "polymerase ii transcription pre initiation", "ii transcription pre initiation and", "transcription pre initiation and promoter", "pre initiation and promoter opening", "formation of", "of the", "the pre", "initiation 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" ] }, { "record_id": "GLY_000594_1_591", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75815", "r hsa", "hsa 75815", "r hsa 75815" ] }, { "record_id": "GLY_000594_1_591", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ubiquitin dependent", "dependent degradation", "degradation of", "of cyclin", "cyclin d", "ubiquitin dependent degradation", "dependent degradation of", "degradation of cyclin", "of cyclin d", "ubiquitin dependent degradation of", "dependent degradation of cyclin", "degradation of cyclin d", "ubiquitin dependent degradation of cyclin", "dependent degradation of cyclin d", "d turnover", "turnover is", "is regulated", "by ubiquitination", "ubiquitination and", "and proteasomal", "proteasomal degradation", "degradation which", "which are", "are positively", "positively regulated", "regulated by", "by cyclin", "d phosphorylation", "phosphorylation on", "on threonine", "threonine 286", "diehl et", "et al.", "1997 .

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coa.", "c16:0 coa. in a", "coa. in a series of", "in a series of less", "a series of less well", "series of less well characterized", "of less well characterized reactions", "less well characterized reactions in", "well characterized reactions in the", "characterized reactions in the cytosol", "reactions in the cytosol and", "in the cytosol and endoplasmic", "the cytosol and endoplasmic reticulum", "and endoplasmic reticulum these", "endoplasmic reticulum these molecules", "reticulum these molecules are", "these molecules are converted to", "molecules are converted to ether", "are converted to ether lipids", "to ether lipids plasmalogens", "ether lipids plasmalogens .", "lipids plasmalogens . the", "plasmalogens . the functions of", ". the functions of plasmalogens", "the functions of plasmalogens are", "functions of plasmalogens are not", "of plasmalogens are not well", "plasmalogens are not well understood.", "are not well understood. they", "not well understood. they are", "well understood. they are an", "understood. they are an abundant", "they are an abundant subclass", "are an abundant subclass of", "an abundant subclass of phospholipids", "subclass of phospholipids however", "phospholipids however and", "however and defects in", "and defects in their metabolism", "defects in their metabolism are", "in their metabolism are associated", "their metabolism are associated with", "metabolism are associated with serious", "are associated with serious human", "associated with serious human disease", "serious human disease de", "human disease de vet", "disease de vet et", "de vet et al. 1999", "et al. 1999 nagan", "al. 1999 nagan and", "1999 nagan and zoeller", "nagan and zoeller 2001 ." ] }, { "record_id": "GLY_000594_1_594", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75953", "r hsa", "hsa 75953", "r hsa 75953" ] }, { "record_id": "GLY_000594_1_594", "filename": "human_protein_pathways_reactome", 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complex", "not involve open complex formation.", "open complex formation. this", "complex formation. this reaction", "this reaction is sensitive to", "reaction is sensitive to inhibition", "is sensitive to inhibition by", "sensitive to inhibition by single", "to inhibition by single stranded", "inhibition by single stranded oligonucleotides." ] }, { "record_id": "GLY_000594_1_595", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75955", "r hsa", "hsa 75955", "r hsa 75955" ] }, { "record_id": "GLY_000594_1_595", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase ii", "ii transcription", "transcription elongation", "rna polymerase ii", "polymerase ii transcription", "ii transcription elongation", "rna polymerase ii transcription", "polymerase ii transcription elongation", "rna polymerase ii transcription elongation", "the mechanisms", "mechanisms governing", "governing 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polymerase during the", "polymerase during the transcription", "during the transcription cycle.", "transcription cycle. komarnitsky", "cycle. komarnitsky et", "et al. 2000", "al. 2000 .", "2000 . komarnitsky", ". komarnitsky et", "komarnitsky et al 2000", "al 2000 arndt", "2000 arndt &", "arndt & kane 2003", "kane 2003 shilatifard", "2003 shilatifard et", "shilatifard et al 2003", "the mechanisms governing the process", "mechanisms governing the process of", "governing the process of elongation", "the process of elongation during", "process of elongation during eukaryotic", "of elongation during eukaryotic mrna", "elongation during eukaryotic mrna synthesis", "during eukaryotic mrna synthesis are", "eukaryotic mrna synthesis are being", "mrna synthesis are being unraveled", "synthesis are being unraveled by", "are being unraveled by recent", "being unraveled by recent studies.", "unraveled by recent studies. these", "by recent studies. these studies", "recent studies. these studies 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2003 .", "2003 . elongation also", ". elongation also represents", "elongation also represents processive phase", "also represents processive phase of", "represents processive phase of transcription", "processive phase of transcription in", "phase of transcription in which", "of transcription in which the", "transcription in which the activities", "in which the activities of", "which the activities of several", "the activities of several mrna", "activities of several mrna processing", "of several mrna processing factors", "several mrna processing factors are", "mrna processing factors are coupled", "processing factors are coupled to", "factors are coupled to transcription", "are coupled to transcription through", "coupled to transcription through their", "to transcription through their binding", "transcription through their binding to", "through their binding to rna", "their binding to rna polymerase", "to rna polymerase pol", "rna polymerase pol ii", "polymerase pol ii .", "pol ii . 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"of five subunits which", "five subunits which differs", "subunits which differs from", "which differs from the six", "differs from the six subunits", "from the six subunits in", "the six subunits in s.", "six subunits in s. cerevisiae", "in s. cerevisiae in", "s. cerevisiae in human", "cerevisiae in human cells", "in human cells and s.", "human cells and s. pombe.", "and s. pombe. once", "s. pombe. once the", "pombe. once the dna/tfiiia/tfiiic", "once the dna/tfiiia/tfiiic complex is", "the dna/tfiiia/tfiiic complex is formed", "complex is formed brf1", "is formed brf1 tfiiib", "formed brf1 tfiiib joins", "brf1 tfiiib joins the complex", "tfiiib joins the complex and", "joins the complex and this", "the complex and this in", "complex and this in turn", "and this in turn allows", "this in turn allows the", "in turn allows the recruitment", "turn allows the recruitment of", "allows the recruitment of rna", "the recruitment of rna polymerase", "recruitment of rna polymerase iii", "rna polymerase iii bieker", "polymerase iii bieker et", "iii bieker et al.", "bieker et al. 1985", "al. 1985 setzer", "1985 setzer and brown", "setzer and brown 1985", "and brown 1985 ." ] }, { "record_id": "GLY_000594_1_598", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "76066", "r hsa", "hsa 76066", "r hsa 76066" ] }, { "record_id": "GLY_000594_1_598", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase iii", "iii transcription", "transcription initiation", "initiation from", "from type", "type 2", "2 promoter", "rna polymerase iii", "polymerase iii transcription", "iii transcription initiation", "transcription initiation from", "initiation from type", "from type 2", "type 2 promoter", "rna polymerase iii transcription", "polymerase iii transcription initiation", "iii transcription initiation from", "transcription initiation from type", "initiation from type 2", "from 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transcription ." ] }, { "record_id": "GLY_000594_1_599", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "76071", "r hsa", "hsa 76071", "r hsa 76071" ] }, { "record_id": "GLY_000594_1_599", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna polymerase", "polymerase iii", "iii transcription", "transcription initiation", "initiation from", "from type", "type 3", "3 promoter", "rna polymerase iii", "polymerase iii transcription", "iii transcription initiation", "transcription initiation from", "initiation from type", "from type 3", "type 3 promoter", "rna polymerase iii transcription", "polymerase iii transcription initiation", "iii transcription initiation from", "transcription initiation from type", "initiation from type 3", "from type 3 promoter", "rna polymerase iii transcription initiation", "polymerase iii transcription initiation from", "iii transcription initiation from type", "transcription initiation from type 3", "initiation from type 3 promoter", "the metazoan", "metazoan specific", "specific type", "3 promoters", "which are", "are exemplified", "exemplified by", "by the", "the human", "human u6", "u6 promoter", "recruit a", "a complex", "complex variously", "variously called", "called the", "the snrna", "snrna activating", "activating protein", "protein complex", "sadowski et", "et al.", "the pse", "pse binding", "binding protein", "waldschmidt et", "or the", "pse transcription", "transcription factor", "murphy et", "1992 .", "the complex", "complex contains", "contains five", "five types", "types of", "of subunits", "subunits and", "and binds", "binds to", "to the", "the pse.", "promoters also", "also recruit", "recruit brf2", "brf2 tfiiib", "tfiiib through", "through a", "a combination", "combination of", "of protein", "protein protein", "protein contacts", "contacts with", "with snapc", "snapc and", "and a", "a direct", "direct association", "association of", "of the", "the tbp", "tbp component", "component of", "of brf2", "tfiiib with", "with the", "the tata", "tata box.", "this then", "then allows", "allows rna", "iii to", "to join", "join the", "the complex.

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the", "the complex.

the down", "complex.

the down stream", "down stream element", "element dse", "dse of", "of type 3", "which enhances transcription", "enhances transcription from", "transcription from the", "from the core", "the core promoter", "promoter almost", "almost invariably contains", "invariably contains an", "contains an octamer", "an octamer sequence", "octamer sequence and", "sequence and an", "and an sph", "an sph element", "element also", "also called nonoct", "called nonoct element", "element cheung", "cheung et al.", "1993 danzeiser", "danzeiser et al.", "1993 kunkel", "kunkel et al.", "al. 1996", "1996 myslinski", "myslinski et al.", "the octamer sequence", "octamer sequence recruits", "sequence recruits the", "recruits the pou", "the pou domain", "pou domain protein", "domain protein oct", "protein oct 1", "1 herr", "herr et al.", "al. 1988", "1988 sturm", "sturm et al.", "and the sph", "the sph element", "sph element recruits", "element recruits a", "recruits a zinc", "a zinc finger", "zinc finger protein", "finger protein known", "protein known as", "known as staf", "as staf or", "staf or sph", "or sph binding", "sph binding factor", "factor sbf", "which has been", "has been cloned", "been cloned from", "cloned from humans", "humans myslinski", "al. 1998", "1998 rincon", "rincon et al.", "the metazoan specific type", "metazoan specific type 3", "specific type 3 promoters", "3 promoters which", "promoters which are", "which are exemplified by", "are exemplified by the", "exemplified by the human", "by the human u6", "the human u6 promoter", "u6 promoter recruit", "promoter recruit a", "recruit a complex variously", "a complex variously called", "complex variously called the", "variously called the snrna", "called the snrna activating", "the snrna activating protein", "snrna activating protein complex", "protein complex snapc", "snapc sadowski", "et al. 1993", "1993 the", "the pse binding protein", "binding protein pbp", "pbp waldschmidt", "et al. 1991", "1991 or", "or the pse transcription", "the pse transcription factor", "transcription factor ptf", "ptf murphy", "et al. 1992", "al. 1992 .", "1992 . the", ". the complex", "the complex contains five", "complex contains five types", "contains five types of", "five types of subunits", "types of subunits and", "of subunits and binds", "subunits and binds to", "and binds to the", "binds to the pse.", "the pse. type", "pse. type 3", "type 3 promoters also", "3 promoters also recruit", "promoters also recruit brf2", "also recruit brf2 tfiiib", "recruit brf2 tfiiib through", "brf2 tfiiib through a", "tfiiib through a combination", "through a combination of", "a combination of protein", "combination of protein protein", "of protein protein contacts", "protein protein contacts with", "protein contacts with snapc", "contacts with snapc and", "with snapc and a", "snapc and a direct", "and a direct association", "a direct association of", "direct association of the", "association of the tbp", "of the tbp component", "the tbp component of", "tbp component of brf2", "component of brf2 tfiiib", "of brf2 tfiiib with", "brf2 tfiiib with the", "tfiiib with the tata", "with the tata box.", "tata box. this", "box. this then", "this then allows rna", "then allows rna polymerase", "allows rna polymerase iii", "rna polymerase iii to", "polymerase iii to join", "iii to join the", "to join the complex.

the", "join the complex.

the down", "the complex.

the down stream", "complex.

the down stream element", "stream element dse", "dse of type", "of type 3 promoters", "promoters which enhances", "which enhances transcription from", "enhances transcription from the", "transcription from the core", "from the core promoter", "core promoter almost", "promoter almost invariably", "almost invariably contains an", "invariably contains an octamer", "contains an octamer sequence", "an octamer sequence and", "octamer sequence and an", "sequence and an sph", "and an sph element", "sph element also", "element also called", "also called nonoct element", "nonoct element cheung", "element cheung et", "1993 danzeiser et", "1993 kunkel et", "et al. 1996", "1996 myslinski et", ". the octamer", "the octamer sequence recruits", "octamer sequence recruits the", "sequence recruits the pou", "recruits the pou domain", "the pou domain protein", "pou domain protein oct", "domain protein oct 1", "oct 1 herr", "1 herr et", "et al. 1988", "1988 sturm et", "1988 and", "and the sph element", "the sph element recruits", "sph element recruits a", "element recruits a zinc", "recruits a zinc finger", "a zinc finger protein", "zinc finger protein known", "finger protein known as", "protein known as staf", "known as staf or", "as staf or sph", "staf or sph binding", "or sph binding factor", "binding factor sbf", "sbf which", "which has been cloned", "has been cloned from", "been cloned from humans", "from humans myslinski", "humans myslinski et", "et al. 1998", "1998 rincon et", "al. 1998 .", "the metazoan specific type 3", "metazoan specific type 3 promoters", "type 3 promoters which", "3 promoters which are", "promoters which are exemplified", "which are exemplified by the", "are exemplified by the human", "exemplified by the human u6", "by the human u6 promoter", "human u6 promoter recruit", "u6 promoter recruit a", "promoter recruit a complex", "recruit a complex variously called", "a complex variously called the", "complex variously called the snrna", "variously called the snrna activating", "called the snrna activating protein", "the snrna activating protein complex", "activating protein complex snapc", "snapc sadowski et", "sadowski et al. 1993", "1993 the pse", "pse binding protein pbp", "pbp waldschmidt et", "waldschmidt et al. 1991", "1991 or the", "or the pse transcription factor", "pse transcription factor ptf", "ptf murphy et", "murphy et al. 1992", "et al. 1992 .", "1992 . the complex", ". the complex contains", "the complex contains five types", "complex contains five types of", "contains five types of subunits", "five types of subunits and", "types of subunits and binds", "of subunits and binds to", "subunits and binds to the", "and binds to the pse.", "to the pse. type", "the pse. type 3", "pse. type 3 promoters", "type 3 promoters also recruit", "3 promoters also recruit brf2", "promoters also recruit brf2 tfiiib", "also recruit brf2 tfiiib through", "recruit brf2 tfiiib through a", "brf2 tfiiib through a combination", "tfiiib through a combination of", "through a combination of protein", "a combination of protein protein", "combination of protein protein contacts", "of protein protein contacts with", "protein protein contacts with snapc", "protein contacts with snapc and", "contacts with snapc and a", "with snapc and a direct", "snapc and a direct association", "and a direct association of", "a direct association of the", "direct association of the tbp", "association of the tbp component", "of the tbp component of", "the tbp component of brf2", "tbp component of brf2 tfiiib", "component of brf2 tfiiib with", "of brf2 tfiiib with the", "brf2 tfiiib with the tata", "tfiiib with the tata box.", "the tata box. this", "tata box. this then", "box. this then allows", "this then allows rna polymerase", "then allows rna polymerase iii", "allows rna polymerase iii to", "rna polymerase iii to join", "polymerase iii to join the", "iii to join the complex.

the", "to join the complex.

the down", "join the complex.

the down stream", "the complex.

the down stream element", "down stream element dse", "element dse of", "dse of type 3", "3 promoters which enhances", "promoters which enhances transcription", "which enhances transcription from the", "enhances transcription from the core", "transcription from the core promoter", "the core promoter almost", "core promoter almost invariably", "promoter almost invariably contains", "almost invariably contains an octamer", "invariably contains an octamer sequence", "contains an octamer sequence and", "an octamer sequence and an", "octamer sequence and an sph", "sequence and an sph element", "an sph element also", "sph element also called", "element also called nonoct", "called nonoct element cheung", "nonoct element cheung et", "element cheung et al.", "cheung et al. 1993", "al. 1993 danzeiser", "1993 danzeiser et al.", "danzeiser et al. 1993", "al. 1993 kunkel", "1993 kunkel et al.", "kunkel et al. 1996", "al. 1996 myslinski", "1996 myslinski et al.", "myslinski et al. 1992", "1992 . the octamer", ". the octamer sequence", "the octamer sequence recruits the", "octamer sequence recruits the pou", "sequence recruits the pou domain", "recruits the pou domain protein", "the pou domain protein oct", "pou domain protein oct 1", "protein oct 1 herr", "oct 1 herr et", "1 herr et al.", "herr et al. 1988", "al. 1988 sturm", "1988 sturm et al.", "sturm et al. 1988", "1988 and the", "and the sph element recruits", "the sph element recruits a", "sph element recruits a zinc", "element recruits a zinc finger", "recruits a zinc finger protein", "a zinc finger protein known", "zinc finger protein known as", "finger protein known as staf", "protein known as staf or", "known as staf or sph", "as staf or sph binding", "staf or sph binding factor", "sph binding factor sbf", "sbf which has", "which has been cloned from", "has been cloned from humans", "cloned from humans myslinski", "from humans myslinski et", "humans myslinski et al.", "myslinski et al. 1998", "al. 1998 rincon", "1998 rincon et al.", "rincon et al. 1998", "et al. 1998 ." ] }, { "record_id": "GLY_000594_1_600", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77075", "r hsa", "hsa 77075", "r hsa 77075" ] }, { "record_id": "GLY_000594_1_600", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rna pol", "pol ii", "ii ctd", "ctd phosphorylation", "phosphorylation and", "and interaction", "interaction with", "with ce", "rna pol ii", "pol ii ctd", "ii ctd phosphorylation", "ctd phosphorylation and", "phosphorylation and interaction", "and interaction with", "interaction with ce", "rna pol ii ctd", "pol ii ctd phosphorylation", "ii ctd phosphorylation and", "ctd phosphorylation and interaction", "phosphorylation and interaction with", "and interaction with ce", "rna pol ii ctd phosphorylation", "pol ii ctd phosphorylation and", "ii ctd phosphorylation and interaction", "ctd phosphorylation and interaction with", "phosphorylation and interaction with ce", "to facilitate", "facilitate co", "co transcriptional", "transcriptional capping", "and thereby", "thereby restrict", "restrict the", "the cap", "cap structure", "structure to", "to rnas", "rnas made", "made by", "by rna", "rna polymerase", "polymerase ii", "the capping", "capping enzymes", "enzymes bind", "bind directly", "directly to", "to the", "the rna", "polymerase ii.", "the c", "c terminal", "terminal domain", "domain of", "of the", "the largest", "largest pol", "ii subunit", "subunit contains", "contains several", "several phosphorylation", "phosphorylation sites", "sites on", "on its", "its heptapeptide", "heptapeptide repeats.", "capping enzyme", "enzyme guanylyltransferase", "guanylyltransferase and", "and the", "the methyltransferase", "methyltransferase bind", "specifically to", "to ctd", "ctd phosphorylated", "phosphorylated at", "at serine", "serine 5", "5 within", "within the", "the ctd.", "kinase subunit", "subunit of", "of 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has been", "has been shown", "been shown that", "shown that binding", "that binding of", "binding of capping", "of capping enzyme", "capping enzyme to", "enzyme to the", "to the serine", "the serine 5", "serine 5 phosphorylated", "5 phosphorylated ctd", "phosphorylated ctd stimulates", "ctd stimulates guanylyltransferase", "stimulates guanylyltransferase activity", "guanylyltransferase activity in", "activity in vitro.", "to facilitate co transcriptional", "facilitate co transcriptional capping", "transcriptional capping and", "capping and thereby", "and thereby restrict the", "thereby restrict the cap", "restrict the cap structure", "the cap structure to", "cap structure to rnas", "structure to rnas made", "to rnas made by", "rnas made by rna", "made by rna polymerase", "by rna polymerase ii", "polymerase ii the", "ii the capping", "the capping enzymes bind", "capping enzymes bind directly", "enzymes bind directly to", "bind directly to the", "directly to the rna", "to the rna polymerase", "the rna polymerase ii.", "polymerase ii. the", "ii. the c", "the c terminal domain", "c terminal domain of", "terminal domain of the", "domain of the largest", "of the largest pol", "the largest pol ii", "largest pol ii subunit", "pol ii subunit contains", "ii subunit contains several", "subunit contains several phosphorylation", "contains several phosphorylation sites", "several phosphorylation sites on", "phosphorylation sites on its", "sites on its heptapeptide", "on its heptapeptide repeats.", "heptapeptide repeats. the", "repeats. the capping", "the capping enzyme guanylyltransferase", "capping enzyme guanylyltransferase and", "enzyme guanylyltransferase and the", "guanylyltransferase and the methyltransferase", "and the methyltransferase bind", "methyltransferase bind specifically", "bind specifically to", "specifically to ctd phosphorylated", "to ctd phosphorylated at", "ctd phosphorylated at serine", "phosphorylated at serine 5", "at serine 5 within", "serine 5 within the", "5 within the ctd.", "the ctd. kinase", "ctd. kinase subunit", "kinase subunit of tfiih", "of tfiih cdk7", "cdk7 catalyzes this", "catalyzes this phosphorylation event", "this phosphorylation event that", "phosphorylation event that occurs", "event that occurs near", "that occurs near the", "occurs near the promoter.", "the promoter. in", "promoter. in addition", "in addition it", "addition it has", "it has been shown", "has been shown that", "been shown that binding", "shown that binding of", "that binding of capping", "binding of capping enzyme", "of capping enzyme to", "capping enzyme to the", "enzyme to the serine", "to the serine 5", "the serine 5 phosphorylated", "serine 5 phosphorylated ctd", "5 phosphorylated ctd stimulates", "phosphorylated ctd stimulates guanylyltransferase", "ctd stimulates guanylyltransferase activity", "stimulates guanylyltransferase activity in", "guanylyltransferase activity in vitro.", "to facilitate co transcriptional capping", "co transcriptional capping and", "transcriptional capping and thereby", "capping and thereby restrict", "and thereby restrict the cap", "thereby restrict the cap structure", "restrict the cap structure to", "the cap structure to rnas", "cap structure to rnas made", "structure to rnas made by", "to rnas made by rna", "rnas made by rna polymerase", "made by rna polymerase ii", "rna polymerase ii the", "polymerase ii the capping", "ii the capping enzymes", "the capping enzymes bind directly", "capping enzymes bind directly to", "enzymes bind directly to the", "bind directly to the rna", "directly to the rna polymerase", "to the rna polymerase ii.", "rna polymerase ii. the", "polymerase ii. the c", "ii. the c terminal", "the c terminal domain of", "c terminal domain of the", "terminal domain of the largest", "domain of the largest pol", "of the largest pol ii", "the largest pol ii subunit", "largest pol ii subunit contains", "pol ii subunit contains several", "ii subunit contains several phosphorylation", "subunit contains several phosphorylation sites", "contains several phosphorylation sites on", "several phosphorylation sites on its", "phosphorylation sites on its heptapeptide", "sites on its heptapeptide repeats.", "its heptapeptide repeats. the", "heptapeptide repeats. the capping", "repeats. the capping enzyme", "the capping enzyme guanylyltransferase and", "capping enzyme guanylyltransferase and the", "enzyme guanylyltransferase and the methyltransferase", "guanylyltransferase and the methyltransferase bind", "the methyltransferase bind specifically", "methyltransferase bind specifically to", "bind specifically to ctd", "specifically to ctd phosphorylated at", "to ctd phosphorylated at serine", "ctd phosphorylated at serine 5", "phosphorylated at serine 5 within", "at serine 5 within the", "serine 5 within the ctd.", "within the ctd. kinase", "the ctd. kinase subunit", "ctd. kinase subunit of", "subunit of tfiih cdk7", "tfiih cdk7 catalyzes", "cdk7 catalyzes this phosphorylation", "catalyzes this phosphorylation event that", "this phosphorylation event that occurs", "phosphorylation event that occurs near", "event that occurs near the", "that occurs near the promoter.", "near the promoter. in", "the promoter. in addition", "in addition it has", "addition it has been", "it has been shown that", "has been shown that binding", "been shown that binding of", "shown that binding of capping", "that binding of capping enzyme", "binding of capping enzyme to", "of capping enzyme to the", "capping enzyme to the serine", "enzyme to the serine 5", "to the serine 5 phosphorylated", "the serine 5 phosphorylated ctd", "serine 5 phosphorylated ctd stimulates", "5 phosphorylated ctd stimulates guanylyltransferase", "phosphorylated ctd stimulates guanylyltransferase activity", "ctd stimulates guanylyltransferase activity in", "stimulates guanylyltransferase activity in vitro." ] }, { "record_id": "GLY_000594_1_601", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77289", "r hsa", "hsa 77289", "r hsa 77289" ] }, { "record_id": "GLY_000594_1_601", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitochondrial fatty", "fatty acid", "acid beta", "beta oxidation", "mitochondrial fatty acid", "fatty acid beta", "acid beta oxidation", "mitochondrial fatty acid beta", "fatty acid beta oxidation", "mitochondrial fatty acid beta oxidation", "oxidation begins", "begins once", "once fatty", "fatty acids", "acids have", "have been", "been imported", "imported into", "into the", "the mitochondrial", "mitochondrial matrix", "matrix by", "by carnitine", "carnitine acyltransferases.", "acyltransferases. the", "the beta", "oxidation spiral", "spiral of", "of fatty", "acids metabolism", "metabolism involves", "involves the", "the repetitive", "repetitive removal", "removal of", "of two", "two carbon", "carbon units", "units from", "from 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beta", "atps.

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beta", "129 atps.

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consumes intermediates with a", "consumes intermediates with a trans", "intermediates with a trans configuration", "a trans configuration unsaturated", "trans configuration unsaturated fatty", "configuration unsaturated fatty acids", "unsaturated fatty acids that have", "fatty acids that have bonds", "acids that have bonds in", "that have bonds in the", "have bonds in the cis", "bonds in the cis configuration", "in the cis configuration require", "the cis configuration require three", "cis configuration require three separate", "configuration require three separate enzymatic", "require three separate enzymatic steps", "three separate enzymatic steps to", "separate enzymatic steps to prepare", "enzymatic steps to prepare these", "steps to prepare these molecules", "to prepare these molecules for", "prepare these molecules for the", "these molecules for the beta", "molecules for the beta oxidation", "for the beta oxidation pathway." ] }, { "record_id": "GLY_000594_1_602", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77387", "r hsa", "hsa 77387", "r hsa 77387" ] }, { "record_id": "GLY_000594_1_602", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "insulin receptor", "receptor recycling", "insulin receptor recycling", "triggered by", "by acidification", "acidification of", "of the", "the endosome", "insulin dissociates", "dissociates from", "from the", "the receptor", "receptor and", "and is", "is degraded.", "degraded. the", "receptor is", "is dephosphorylated", "dephosphorylated and", "and re", "re integrated", "integrated into", "into the", "the plasma", "plasma membrane", "ready to", "to be", "be activated", "activated again", "again by", "by the", "the binding", "binding of", "of insulin", "insulin molecules.", "triggered by acidification", "by acidification of", "acidification of the", "of the endosome", "endosome insulin", "insulin dissociates from", "dissociates 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"dephosphorylated and re integrated into", "and re integrated into the", "re integrated into the plasma", "integrated into the plasma membrane", "the plasma membrane ready", "plasma membrane ready to", "membrane ready to be", "ready to be activated again", "to be activated again by", "be activated again by the", "activated again by the binding", "again by the binding of", "by the binding of insulin", "the binding of insulin molecules." ] }, { "record_id": "GLY_000594_1_603", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "83936", "r hsa", "hsa 83936", "r hsa 83936" ] }, { "record_id": "GLY_000594_1_603", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transport of", "of nucleosides", "nucleosides and", "and free", "free purine", "purine and", "and pyrimidine", "pyrimidine bases", "bases across", "across the", "the plasma", "plasma membrane", "transport of nucleosides", "of nucleosides and", "nucleosides and free", "and free purine", "free purine and", "purine and pyrimidine", "and pyrimidine bases", "pyrimidine bases across", "bases across the", "across the plasma", "the plasma membrane", "transport of nucleosides and", "of nucleosides and free", "nucleosides and free purine", "and free purine and", "free purine and pyrimidine", "purine and pyrimidine bases", "and pyrimidine bases across", "pyrimidine bases across the", "bases across the plasma", "across the plasma membrane", "transport of nucleosides and free", "of nucleosides and free purine", "nucleosides and free purine and", "and free purine and pyrimidine", "free purine and pyrimidine bases", "purine and pyrimidine bases across", "and pyrimidine bases across the", "pyrimidine bases across the plasma", "bases across the plasma membrane", "two families", "families of", "of transport", "transport proteins", "proteins mediate", "mediate the", "the movement", "movement of", "plasma membrane.", "equilibrative nucleoside", "nucleoside transporters", "transporters allow", "allow the", "of these", "these molecules", "molecules along", "along concentration", "concentration gradients", "gradients into", "into or", "or out", "out of", "of cells", "baldwin et", "et al.", "al. 2003", "concentrative nucleoside", "transporters actively", "actively transport", "transport nucleosides", "nucleosides into", "into cells", "cells by", "by coupling", "coupling their", "their transport", "transport to", "to the", "the inward", "inward movement", "of sodium", "sodium ions", "gray et", "2003 .

of", ".

of the", "the four", "four human", "human equilibrative", "two are", "are well", "well characterized.", "solute carrier", "carrier family", "family 29", "member 1", "mediates the", "the transport", "nucleosides across", "member 2", "of both", "both nucleosides", "free bases.", "transporter specificities", "specificities were", "were determined", "determined by", "by expressing", "expressing cloned", "cloned human", "human genes", "genes in", "in xenopus", "xenopus oocytes", "oocytes or", "or in", "in mammalian", "mammalian cultured", "cultured cell", "cell lines", "lines whose", "whose own", "own nucleotide", "nucleotide transporters", "transporters had", "had been", "been disrupted", "disrupted by", "by mutation.", "these studies", "studies establish", "establish that", "that the", "transport processes", "processes are", "are specific", "specific and", "and saturable", "and that", "the multiple", "multiple nucleotides", "nucleotides and", "and bases", "bases compete", "compete for", "for a", "a single", "single binding", "binding site", "site on", "on each", "each transporter.", "some features", "features of", "slc29a2 specificity", "specificity are", "are complex.", "for example", "in the", "the xenopus", "xenopus oocyte", "oocyte system", "radiolabeled uracil", "uracil and", "and adenine", "adenine are", "are taken", "taken up", "and an", "an excess", "excess of", "of either", "either molecule", "molecule inhibits", "inhibits uptake", "uptake of", "of radiolabeled", "radiolabeled hypoxanthine", "while in", "the cultured", "cultured mammalian", "mammalian cell", "cell system", "neither adenine", "adenine nor", "nor uracil", "uracil can", "can inhibit", "inhibit uptake", "radiolabeled uridine.", "if these", "these results", "results reflect", "reflect ent2", "ent2 function", "function in", "in vivo", "they indicate", "indicate that", "the net", "net movement", "of a", "a nucleoside", "nucleoside or", "or base", "base across", "the cell", "cell membrane", "membrane is", "is determined", "determined not", "not only", "only by", "by its", "its own", "own concentrations", "concentrations in", "the extracellular", "extracellular space", "space and", "and the", "the cytosol", "but also", "also by", "by the", "the concentrations", "concentrations of", "of the", "the other", "other nucleosides", "bases competing", "competing for", "for access", "access to", "the transporter.

the", "transporter.

the human", "human genome", "genome encodes", "encodes three", "three concentrative", "concentrative transporters", "and 3", "family 28", "sodium coupled", "coupled nucleoside", "nucleoside transporter", "3 .", "all three", "three genes", "genes have", "have been", "been cloned", "and expression", "expression of", "the human", "human proteins", "proteins in", "oocytes has", "has allowed", "allowed their", "transport properties", "properties to", "to be", "be determined.", "slc28a1 mediates", "the uptake", "of pyrimidine", "pyrimidine nucleosides", "and adenosine", "ritzel et", "al. 1997", "slc28a2 the", "of purine", "purine nucleosides", "and uridine", "wang et", "and slc28a3", "slc28a3 the", "al. 2001", "2001 .", "amino acid", "acid sequence", "sequence motifs", "motifs that", "that determine", "determine the", "the specificities", "specificities of", "these transporters", "transporters have", "been identified", "identified in", "in studies", "studies of", "of chimeric", "chimeric and", "and mutant", "mutant proteins", "loewen et", "al. 1999", "1999 .", "slc28a3 protein", "protein co", "co transports", "transports two", "two sodium", "ions per", "per nucleoside", "slc28a1 and", "and 2", "2 transport", "transport one", "one sodium", "sodium per", "2001 .

physiological", ".

physiological roles", "roles for", "for nucleoside", "nucleoside and", "and base", "base transport", "transport include", "include provision", "provision of", "nucleosides to", "to cells", "cells with", "with little", "little capacity", "capacity to", "to synthesize", "synthesize these", "molecules de", "de novo", "and regulation", "regulation of", "of extracellular", "extracellular levels", "levels of", "of adenosine", "which is", "is released", "released from", "from muscle", "muscle during", "during intense", "intense exercise", "exercise and", "and has", "has signaling", "signaling properties.", "in kidney", "kidney and", "and intestinal", "intestinal epithelia", "the combination", "combination of", "of apically", "apically localized", "localized cnt", "cnt transporters", "transporters and", "and basolaterally", "basolaterally localized", "localized ent", "ent transporters", "transporters provides", "provides a", "a mechanism", "mechanism for", "for net", "net transport", "mangravite et", "2003 .", "transporters also", "also mediate", "of nucleoside", "nucleoside analogs", "analogs used", "used clinically", "clinically as", "as anti", "anti viral", "viral and", "and anti", "anti tumor", "tumor drugs.

orthologs", "drugs.

orthologs of", "of human", "human concentrative", "concentrative and", "and equilibrative", "equilibrative transporter", "transporter proteins", "proteins have", "in many", "many eukaryotes", "but functional", "functional studies", "of transporters", "transporters even", "even from", "from organisms", "organisms closely", "closely related", "related to", "to humans", "e.g. rat", "gerstin et", "al. 2002", "have revealed", "revealed differences", "differences in", "in substrate", "substrate specificities.", "prediction of", "of drug", "drug uptake", "uptake and", "and other", "other functions", "functions of", "molecules by", "by human", "model organism", "organism orthology", "orthology is", "is thus", "thus risky.", "two families of", "families of transport", "of transport proteins", "transport proteins mediate", "proteins mediate the", "mediate the movement", "the movement of", "movement of nucleosides", "the plasma membrane.", "membrane. equilibrative", "equilibrative nucleoside transporters", "nucleoside transporters allow", "transporters allow the", "allow the movement", "movement of these", "of these molecules", "these molecules along", "molecules along concentration", "along concentration gradients", "concentration gradients into", "gradients into or", "into or out", "or out of", "out of cells", "cells baldwin", "baldwin et al.", "et al. 2003", "concentrative nucleoside transporters", "nucleoside transporters actively", "transporters actively transport", "actively transport nucleosides", "transport nucleosides into", "nucleosides into cells", "into cells by", "cells by coupling", "by coupling their", "coupling their transport", "their transport to", "transport to the", "to the inward", "the inward movement", "inward movement of", "movement of sodium", "of sodium ions", "ions gray", "gray et al.", "al. 2003 .

of", "2003 .

of the", ".

of the four", "the four human", "four human equilibrative", "human equilibrative nucleoside", "transporters two", "two are well", "are well characterized.", "characterized. slc29a1", "slc29a1 solute", "solute carrier family", "carrier family 29", "29 nucleoside", "1 mediates", "mediates the transport", "the transport of", "of nucleosides across", "nucleosides across the", "membrane. slc29a2", "slc29a2 solute", "2 mediates", "transport of both", "of both nucleosides", "both nucleosides and", "and free bases.", "bases. transporter", "transporter specificities were", "specificities were determined", "were determined by", "determined by expressing", "by expressing cloned", "expressing cloned human", "cloned human genes", "human genes in", "genes in xenopus", "in xenopus oocytes", "xenopus oocytes or", "oocytes or in", "or in mammalian", "in mammalian cultured", "mammalian cultured cell", "cultured cell lines", "cell lines whose", "lines whose own", "whose own nucleotide", "own nucleotide transporters", "nucleotide transporters had", "transporters had been", "had been disrupted", "been disrupted by", "disrupted by mutation.", "mutation. these", "these studies establish", "studies establish that", "establish that the", "that the transport", "the transport processes", "transport processes are", "processes are specific", "are specific and", "specific and saturable", "saturable and", "and that the", "that the multiple", "the multiple nucleotides", "multiple nucleotides and", "nucleotides and bases", "and bases compete", "bases compete for", "compete for a", "for a single", "a single binding", "single binding site", "binding site on", "site on each", "on each transporter.", "transporter. some", "some features of", "of slc29a2", "slc29a2 specificity are", "specificity are complex.", "complex. for", "example in", "in the xenopus", "the xenopus oocyte", "xenopus oocyte system", "system radiolabeled", "radiolabeled uracil and", "uracil and adenine", "and adenine are", "adenine are taken", "are taken up", "up and", "and an excess", "an excess of", "excess of either", "of either molecule", "either molecule inhibits", "molecule inhibits uptake", "inhibits uptake of", "uptake of radiolabeled", "of radiolabeled hypoxanthine", "hypoxanthine while", "while in the", "in the cultured", "the cultured mammalian", "cultured mammalian cell", "mammalian cell system", "system neither", "neither adenine nor", "adenine nor uracil", "nor uracil can", "uracil can inhibit", "can inhibit uptake", "inhibit uptake of", "of radiolabeled uridine.", "uridine. if", "if these results", "these results reflect", "results reflect ent2", "reflect ent2 function", "ent2 function in", "function in vivo", "vivo they", "they indicate that", "indicate that the", "that the net", "the net movement", "net movement of", "movement of a", "of a nucleoside", "a nucleoside or", "nucleoside or base", "or base across", "base across the", "across the cell", "the cell membrane", "cell membrane is", "membrane is determined", "is determined not", "determined not only", "not only by", "only by its", "by its own", "its own concentrations", "own concentrations in", "concentrations in the", "in the extracellular", "the extracellular space", "extracellular space and", "space and the", "and the cytosol", "cytosol but", "but also by", "also by the", "by the concentrations", "the concentrations of", "concentrations of the", "of the other", "the other nucleosides", "other nucleosides and", "nucleosides and bases", "and bases competing", "bases competing for", "competing for access", "for access to", "access to the", "to the transporter.

the", "the transporter.

the human", "transporter.

the human genome", "human genome encodes", "genome encodes three", "encodes three concentrative", "three concentrative transporters", "transporters slc28a1", "slc28a1 2", "2 and", "3 solute", "carrier family 28", "28 sodium", "sodium coupled nucleoside", "coupled nucleoside transporter", "1 2", "and 3 .", ". all", "all three genes", "three genes have", "genes have been", "have been cloned", "cloned and", "and expression of", "expression of the", "of the human", "the human proteins", "human proteins in", "proteins in xenopus", "xenopus oocytes has", "oocytes has allowed", "has allowed their", "allowed their transport", "their transport properties", "transport properties to", "properties to be", "to be determined.", "determined. slc28a1", "slc28a1 mediates the", "mediates the uptake", "the uptake of", "uptake of pyrimidine", "of pyrimidine nucleosides", "pyrimidine nucleosides and", "nucleosides and adenosine", "adenosine ritzel", "ritzel et al.", "et al. 1997", "slc28a2 the uptake", "uptake of purine", "of purine nucleosides", "purine nucleosides and", "nucleosides and uridine", "uridine wang", "wang et al.", "and slc28a3 the", "slc28a3 the uptake", "of purine and", "and pyrimidine nucleosides", "nucleosides ritzel", "et al. 2001", "al. 2001 .", ". amino", "amino acid sequence", "acid sequence motifs", "sequence motifs that", "motifs that determine", "that determine the", "determine the specificities", "the specificities of", "specificities of these", "of these transporters", "these transporters have", "transporters have been", "have been identified", "been identified in", "identified in studies", "in studies of", "studies of chimeric", "of chimeric and", "chimeric and mutant", "and mutant proteins", "proteins loewen", "loewen et al.", "et al. 1999", "al. 1999 .", ". slc28a3", "slc28a3 protein co", "protein co transports", "co transports two", "transports two sodium", "two sodium ions", "sodium ions per", "ions per nucleoside", "nucleoside slc28a1", "slc28a1 and 2", "and 2 transport", "2 transport one", "transport one sodium", "one sodium per", "sodium per nucleoside", "nucleoside ritzel", "al. 2001 .

physiological", "2001 .

physiological roles", ".

physiological roles for", "roles for nucleoside", "for nucleoside and", "nucleoside and base", "and base transport", "base transport include", "transport include provision", "include provision of", "provision of nucleosides", "of nucleosides to", "nucleosides to cells", "to cells with", "cells with little", "with little capacity", "little capacity to", "capacity to synthesize", "to synthesize these", "synthesize these molecules", "these molecules de", "molecules de novo", "novo and", "and regulation of", "regulation of extracellular", "of extracellular levels", "extracellular levels of", "levels of adenosine", "adenosine which", "which is released", "is released from", "released from muscle", "from muscle during", "muscle during intense", "during intense exercise", "intense exercise and", "exercise and has", "and has signaling", "has signaling properties.", "properties. in", "in kidney and", "kidney and intestinal", "and intestinal epithelia", "epithelia the", "the combination of", "combination of apically", "of apically localized", "apically localized cnt", "localized cnt transporters", "cnt transporters and", "transporters and basolaterally", "and basolaterally localized", "basolaterally localized ent", "localized ent transporters", "ent transporters provides", "transporters provides a", "provides a mechanism", "a mechanism for", "mechanism for net", "for net transport", "net transport of", "nucleosides mangravite", "mangravite et al.", "al. 2003 .", ". these", "these transporters also", "transporters also mediate", "also mediate the", "mediate the uptake", "uptake of nucleoside", "of nucleoside analogs", "nucleoside analogs used", "analogs used clinically", "used clinically as", "clinically as anti", "as anti viral", "anti viral and", "viral and anti", "and anti tumor", "anti tumor drugs.

orthologs", "tumor drugs.

orthologs of", "drugs.

orthologs of human", "of human concentrative", "human concentrative and", "concentrative and equilibrative", "and equilibrative transporter", "equilibrative transporter proteins", "transporter proteins have", "proteins have been", "identified in many", "in many eukaryotes", "eukaryotes but", "but functional studies", "functional studies of", "studies of transporters", "of transporters even", "transporters even from", "even from organisms", "from organisms closely", "organisms closely related", "closely related to", "related to humans", "humans e.g.", "rat gerstin", "gerstin et al.", "et al. 2002", "2002 have", "have revealed differences", "revealed differences in", "differences in substrate", "in substrate specificities.", "specificities. prediction", "prediction of drug", "of drug uptake", "drug uptake and", "uptake and other", "and other functions", "other functions of", "functions of these", "these molecules by", "molecules by human", "model organism orthology", "organism orthology is", "orthology is thus", "is thus risky.", "two families of transport", "families of transport proteins", "of transport proteins mediate", "transport proteins mediate the", "proteins mediate the movement", "mediate the movement of", "the movement of nucleosides", "movement of nucleosides and", "across the plasma membrane.", "plasma membrane. equilibrative", "membrane. equilibrative nucleoside", "equilibrative nucleoside transporters allow", "nucleoside transporters allow the", "transporters allow the movement", "allow the movement of", "the movement of these", "movement of these molecules", "of these molecules along", "these molecules along concentration", "molecules along concentration gradients", "along concentration gradients into", "concentration gradients into or", "gradients into or out", "into or out of", "or out of cells", "of cells baldwin", "cells baldwin et", "baldwin et al. 2003", "2003 concentrative", "concentrative nucleoside transporters actively", "nucleoside transporters actively transport", "transporters actively transport nucleosides", "actively transport nucleosides into", "transport nucleosides into cells", "nucleosides into cells by", "into cells by coupling", "cells by coupling their", "by coupling their transport", "coupling their transport to", "their transport to the", "transport to the inward", "to the inward movement", "the inward movement of", "inward movement of sodium", "movement of sodium ions", "sodium ions gray", "ions gray et", "gray et al. 2003", "et al. 2003 .

of", "al. 2003 .

of the", "2003 .

of the four", ".

of the four human", "the four human equilibrative", "four human equilibrative nucleoside", "human equilibrative nucleoside transporters", "nucleoside transporters two", "transporters two are", "two are well characterized.", "well characterized. slc29a1", "slc29a1 solute carrier", "solute carrier family 29", "family 29 nucleoside", "29 nucleoside transporters", "transporters member", "member 1 mediates", "1 mediates the", "mediates the transport of", "the transport of nucleosides", "transport of nucleosides across", "of nucleosides across the", "nucleosides across the plasma", "plasma membrane. slc29a2", "slc29a2 solute carrier", "member 2 mediates", "2 mediates the", "the transport of both", "transport of both nucleosides", "of both nucleosides and", "both nucleosides and free", "nucleosides and free bases.", "free bases. transporter", "bases. transporter specificities", "transporter specificities were determined", "specificities were determined by", "were determined by expressing", "determined by expressing cloned", "by expressing cloned human", "expressing cloned human genes", "cloned human genes in", "human genes in xenopus", "genes in xenopus oocytes", "in xenopus oocytes or", "xenopus oocytes or in", "oocytes or in mammalian", "or in mammalian cultured", "in mammalian cultured cell", "mammalian cultured cell lines", "cultured cell lines whose", "cell lines whose own", "lines whose own nucleotide", "whose own nucleotide transporters", "own nucleotide transporters had", "nucleotide transporters had been", "transporters had been disrupted", "had been disrupted by", "been disrupted by mutation.", "by mutation. these", "mutation. these studies", "these studies establish that", "studies establish that the", "establish that the transport", "that the transport processes", "the transport processes are", "transport processes are specific", "processes are specific and", "are specific and saturable", "and saturable and", "saturable and that", "and that the multiple", "that the multiple nucleotides", "the multiple nucleotides and", "multiple nucleotides and bases", "nucleotides and bases compete", "and bases compete for", "bases compete for a", "compete for a single", "for a single binding", "a single binding site", "single binding site on", "binding site on each", "site on each transporter.", "each transporter. some", "transporter. some features", "features of slc29a2", "of slc29a2 specificity", "slc29a2 specificity are complex.", "are complex. for", "complex. for example", "for example in", "example in the", "in the xenopus oocyte", "the xenopus oocyte system", "oocyte system radiolabeled", "system radiolabeled uracil", "radiolabeled uracil and adenine", "uracil and adenine are", "and adenine are taken", "adenine are taken up", "taken up and", "up and an", "and an excess of", "an excess of either", "excess of either molecule", "of either molecule inhibits", "either molecule inhibits uptake", "molecule inhibits uptake of", "inhibits uptake of radiolabeled", "uptake of radiolabeled hypoxanthine", "radiolabeled hypoxanthine while", "hypoxanthine while in", "while in the cultured", "in the cultured mammalian", "the cultured mammalian cell", "cultured mammalian cell system", "cell system neither", "system neither adenine", "neither adenine nor uracil", "adenine nor uracil can", "nor uracil can inhibit", "uracil can inhibit uptake", "can inhibit uptake of", "inhibit uptake of radiolabeled", "uptake of radiolabeled uridine.", "radiolabeled uridine. if", "uridine. if these", "if these results reflect", "these results reflect ent2", "results reflect ent2 function", "reflect ent2 function in", "ent2 function in vivo", "in vivo they", "vivo they indicate", "they indicate that the", "indicate that the net", "that the net movement", "the net movement of", "net movement of a", "movement of a nucleoside", "of a nucleoside or", "a nucleoside or base", "nucleoside or base across", "or base across the", "base across the cell", "across the cell membrane", "the cell membrane is", "cell membrane is determined", "membrane is determined not", "is determined not only", "determined not only by", "not only by its", "only by its own", "by its own concentrations", "its own concentrations in", "own concentrations in the", "concentrations in the extracellular", "in the extracellular space", "the extracellular space and", "extracellular space and the", "space and the cytosol", "the cytosol but", "cytosol but also", "but also by the", "also by the concentrations", "by the concentrations of", "the concentrations of the", "concentrations of the other", "of the other nucleosides", "the other nucleosides and", "other nucleosides and bases", "nucleosides and bases competing", "and bases competing for", "bases competing for access", "competing for access to", "for access to the", "access to the transporter.

the", "to the transporter.

the human", "the transporter.

the human genome", "transporter.

the human genome encodes", "human genome encodes three", "genome encodes three concentrative", "encodes three concentrative transporters", "concentrative transporters slc28a1", "2 and 3", "and 3 solute", "3 solute carrier", "solute carrier family 28", "family 28 sodium", "28 sodium coupled", "sodium coupled nucleoside transporter", "transporter member", "member 1 2", "3 . all", ". all three", "all three genes have", "three genes have been", "genes have been cloned", "been cloned and", "cloned and expression", "and expression of the", "expression of the human", "of the human proteins", "the human proteins in", "human proteins in xenopus", "proteins in xenopus oocytes", "in xenopus oocytes has", "xenopus oocytes has allowed", "oocytes has allowed their", "has allowed their transport", "allowed their transport properties", "their transport properties to", "transport properties to be", "properties to be determined.", "be determined. slc28a1", "determined. slc28a1 mediates", "slc28a1 mediates the uptake", "mediates the uptake of", "the uptake of pyrimidine", "uptake of pyrimidine nucleosides", "of pyrimidine nucleosides and", "pyrimidine nucleosides and adenosine", "and adenosine ritzel", "adenosine ritzel et", "ritzel et al. 1997", "1997 slc28a2", "slc28a2 the uptake of", "the uptake of purine", "uptake of purine nucleosides", "of purine nucleosides and", "purine nucleosides and uridine", "and uridine wang", "uridine wang et", "wang et al. 1997", "1997 and", "and slc28a3 the uptake", "slc28a3 the uptake of", "uptake of purine and", "of purine and pyrimidine", "purine and pyrimidine nucleosides", "pyrimidine nucleosides ritzel", "nucleosides ritzel et", "ritzel et al. 2001", "et al. 2001 .", "2001 . amino", ". amino acid", "amino acid sequence motifs", "acid sequence motifs that", "sequence motifs that determine", "motifs that determine the", "that determine the specificities", "determine the specificities of", "the specificities of these", "specificities of these transporters", "of these transporters have", "these transporters have been", "transporters have been identified", "have been identified in", "been identified in studies", "identified in studies of", "in studies of chimeric", "studies of chimeric and", "of chimeric and mutant", "chimeric and mutant proteins", "mutant proteins loewen", "proteins loewen et", "loewen et al. 1999", "et al. 1999 .", "1999 . slc28a3", ". slc28a3 protein", "slc28a3 protein co transports", "protein co transports two", "co transports two sodium", "transports two sodium ions", "two sodium ions per", "sodium ions per nucleoside", "per nucleoside slc28a1", "nucleoside slc28a1 and", "slc28a1 and 2 transport", "and 2 transport one", "2 transport one sodium", "transport one sodium per", "one sodium per nucleoside", "per nucleoside ritzel", "nucleoside ritzel et", "et al. 2001 .

physiological", "al. 2001 .

physiological roles", "2001 .

physiological roles for", ".

physiological roles for nucleoside", "roles for nucleoside and", "for nucleoside and base", "nucleoside and base transport", "and base transport include", "base transport include provision", "transport include provision of", "include provision of nucleosides", "provision of nucleosides to", "of nucleosides to cells", "nucleosides to cells with", "to cells with little", "cells with little capacity", "with little capacity to", "little capacity to synthesize", "capacity to synthesize these", "to synthesize these molecules", "synthesize these molecules de", "these molecules de novo", "de novo and", "novo and regulation", "and regulation of extracellular", "regulation of extracellular levels", "of extracellular levels of", "extracellular levels of adenosine", "of adenosine which", "adenosine which is", "which is released from", "is released from muscle", "released from muscle during", "from muscle during intense", "muscle during intense exercise", "during intense exercise and", "intense exercise and has", "exercise and has signaling", "and has signaling properties.", "signaling properties. in", "properties. in kidney", "in kidney and intestinal", "kidney and intestinal epithelia", "intestinal epithelia the", "epithelia the combination", "the combination of apically", "combination of apically localized", "of apically localized cnt", "apically localized cnt transporters", "localized cnt transporters and", "cnt transporters and basolaterally", "transporters and basolaterally localized", "and basolaterally localized ent", "basolaterally localized ent transporters", "localized ent transporters provides", "ent transporters provides a", "transporters provides a mechanism", "provides a mechanism for", "a mechanism for net", "mechanism for net transport", "for net transport of", "net transport of nucleosides", "of nucleosides mangravite", "nucleosides mangravite et", "mangravite et al. 2003", "et al. 2003 .", "2003 . these", ". these transporters", "these transporters also mediate", "transporters also mediate the", "also mediate the uptake", "mediate the uptake of", "the uptake of nucleoside", "uptake of nucleoside analogs", "of nucleoside analogs used", "nucleoside analogs used clinically", "analogs used clinically as", "used clinically as anti", "clinically as anti viral", "as anti viral and", "anti viral and anti", "viral and anti tumor", "and anti tumor drugs.

orthologs", "anti tumor drugs.

orthologs of", "tumor drugs.

orthologs of human", "drugs.

orthologs of human concentrative", "of human concentrative and", "human concentrative and equilibrative", "concentrative and equilibrative transporter", "and equilibrative transporter proteins", "equilibrative transporter proteins have", "transporter proteins have been", "proteins have been identified", "been identified in many", "identified in many eukaryotes", "many eukaryotes but", "eukaryotes but functional", "but functional studies of", "functional studies of transporters", "studies of transporters even", "of transporters even from", "transporters even from organisms", "even from organisms closely", "from organisms closely related", "organisms closely related to", "closely related to humans", "to humans e.g.", "humans e.g. rat", "e.g. rat gerstin", "rat gerstin et", "gerstin et al. 2002", "al. 2002 have", "2002 have revealed", "have revealed differences in", "revealed differences in substrate", "differences in substrate specificities.", "substrate specificities. prediction", "specificities. prediction of", "prediction of drug uptake", "of drug uptake and", "drug uptake and other", "uptake and other functions", "and other functions of", "other functions of these", "functions of these molecules", "of these molecules by", "these molecules by human", "human model", "model organism orthology is", "organism orthology is thus", "orthology is thus risky.", "two families of transport proteins", "families of transport proteins mediate", "of transport proteins mediate the", "transport proteins mediate the movement", "proteins mediate the movement of", "mediate the movement of nucleosides", "the movement of nucleosides and", "movement of nucleosides and free", "bases across the plasma membrane.", "the plasma membrane. equilibrative", "plasma membrane. equilibrative nucleoside", "membrane. equilibrative nucleoside transporters", "equilibrative nucleoside transporters allow the", "nucleoside transporters allow the movement", "transporters allow the movement of", "allow the movement of these", "the movement of these molecules", "movement of these molecules along", "of these molecules along concentration", "these molecules along concentration gradients", "molecules along concentration gradients into", "along concentration gradients into or", "concentration gradients into or out", "gradients into or out of", "into or out of cells", "out of cells baldwin", "of cells baldwin et", "cells baldwin et al.", "al. 2003 concentrative", "2003 concentrative nucleoside", "concentrative nucleoside transporters actively transport", "nucleoside transporters actively transport nucleosides", "transporters actively transport nucleosides into", "actively transport nucleosides into cells", "transport nucleosides into cells by", "nucleosides into cells by coupling", "into cells by coupling their", "cells by coupling their transport", "by coupling their transport to", "coupling their transport to the", "their transport to the inward", "transport to the inward movement", "to the inward movement of", "the inward movement of sodium", "inward movement of sodium ions", "of sodium ions gray", "sodium ions gray et", "ions gray et al.", "gray et al. 2003 .

of", "et al. 2003 .

of the", "al. 2003 .

of the four", "2003 .

of the four human", ".

of the four human equilibrative", "the four human equilibrative nucleoside", "four human equilibrative nucleoside transporters", "equilibrative nucleoside transporters two", "nucleoside transporters two are", "transporters two are well", "are well characterized. slc29a1", "characterized. slc29a1 solute", "slc29a1 solute carrier family", "carrier family 29 nucleoside", "family 29 nucleoside transporters", "nucleoside transporters member", "transporters member 1", "member 1 mediates the", "1 mediates the transport", "mediates the transport of nucleosides", "the transport of nucleosides across", "transport of nucleosides across the", "of nucleosides across the plasma", "nucleosides across the plasma membrane.", "the plasma membrane. slc29a2", "membrane. slc29a2 solute", "slc29a2 solute carrier family", "transporters member 2", "member 2 mediates the", "2 mediates the transport", "mediates the transport of both", "the transport of both nucleosides", "transport of both nucleosides and", "of both nucleosides and free", "both nucleosides and free bases.", "and free bases. transporter", "free bases. transporter specificities", "bases. transporter specificities were", "transporter specificities were determined by", "specificities were determined by expressing", "were determined by expressing cloned", "determined by expressing cloned human", "by expressing cloned human genes", "expressing cloned human genes in", "cloned human genes in xenopus", "human genes in xenopus oocytes", "genes in xenopus oocytes or", "in xenopus oocytes or in", "xenopus oocytes or in mammalian", "oocytes or in mammalian cultured", "or in mammalian cultured cell", "in mammalian cultured cell lines", "mammalian cultured cell lines whose", "cultured cell lines whose own", "cell lines whose own nucleotide", "lines whose own nucleotide transporters", "whose own nucleotide transporters had", "own nucleotide transporters had been", "nucleotide transporters had been disrupted", "transporters had been disrupted by", "had been disrupted by mutation.", "disrupted by mutation. these", "by mutation. these studies", "mutation. these studies establish", "these studies establish that the", "studies establish that the transport", "establish that the transport processes", "that the transport processes are", "the transport processes are specific", "transport processes are specific and", "processes are specific and saturable", "specific and saturable and", "and saturable and that", "saturable and that the", "and that the multiple nucleotides", "that the multiple nucleotides and", "the multiple nucleotides and bases", "multiple nucleotides and bases compete", "nucleotides and bases compete for", "and bases compete for a", "bases compete for a single", "compete for a single binding", "for a single binding site", "a single binding site on", "single binding site on each", "binding site on each transporter.", "on each transporter. some", "each transporter. some features", "transporter. some features of", "some features of slc29a2", "features of slc29a2 specificity", "of slc29a2 specificity are", "specificity are complex. for", "are complex. for example", "for example in the", "example in the xenopus", "in the xenopus oocyte system", "xenopus oocyte system radiolabeled", "oocyte system radiolabeled uracil", "system radiolabeled uracil and", "radiolabeled uracil and adenine are", "uracil and adenine are taken", "and adenine are taken up", "are taken up and", "taken up and an", "up and an excess", "and an excess of either", "an excess of either molecule", "excess of either molecule inhibits", "of either molecule inhibits uptake", "either molecule inhibits uptake of", "molecule inhibits uptake of radiolabeled", "inhibits uptake of radiolabeled hypoxanthine", "of radiolabeled hypoxanthine while", "radiolabeled hypoxanthine while in", "hypoxanthine while in the", "while in the cultured mammalian", "in the cultured mammalian cell", "the cultured mammalian cell system", "mammalian cell system neither", "cell system neither adenine", "system neither adenine nor", "neither adenine nor uracil can", "adenine nor uracil can inhibit", "nor uracil can inhibit uptake", "uracil can inhibit uptake of", "can inhibit uptake of radiolabeled", "inhibit uptake of radiolabeled uridine.", "of radiolabeled uridine. if", "radiolabeled uridine. if these", "uridine. if these results", "if these results reflect ent2", "these results reflect ent2 function", "results reflect ent2 function in", "reflect ent2 function in vivo", "function in vivo they", "in vivo they indicate", "vivo they indicate that", "they indicate that the net", "indicate that the net movement", "that the net movement of", "the net movement of a", "net movement of a nucleoside", "movement of a nucleoside or", "of a nucleoside or base", "a nucleoside or base across", "nucleoside or base across the", "or base across the cell", "base across the cell membrane", "across the cell membrane is", "the cell membrane is determined", "cell membrane is determined not", "membrane is determined not only", "is determined not only by", "determined not only by its", "not only by its own", "only by its own concentrations", "by its own concentrations in", "its own concentrations in the", "own concentrations in the extracellular", "concentrations in the extracellular space", "in the extracellular space and", "the extracellular space and the", "extracellular space and the cytosol", "and the cytosol but", "the cytosol but also", "cytosol but also by", "but also by the concentrations", "also by the concentrations of", "by the concentrations of the", "the concentrations of the other", "concentrations of the other nucleosides", "of the other nucleosides and", "the other nucleosides and bases", "other nucleosides and bases competing", "nucleosides and bases competing for", "and bases competing for access", "bases competing for access to", "competing for access to the", "for access to the transporter.

the", "access to the transporter.

the human", "to the transporter.

the human genome", "the transporter.

the human genome encodes", "transporter.

the human genome encodes three", "human genome encodes three concentrative", "genome encodes three concentrative transporters", "three concentrative transporters slc28a1", "transporters slc28a1 2", "slc28a1 2 and", "and 3 solute carrier", "3 solute carrier family", "carrier family 28 sodium", "family 28 sodium coupled", "28 sodium coupled nucleoside", "nucleoside transporter member", "transporter member 1", "1 2 and", "2 and 3 .", "and 3 . all", "3 . all three", ". all three genes", "all three genes have been", "three genes have been cloned", "have been cloned and", "been cloned and expression", "cloned and expression of", "and expression of the human", "expression of the human proteins", "of the human proteins in", "the human proteins in xenopus", "human proteins in xenopus oocytes", "proteins in xenopus oocytes has", "in xenopus oocytes has allowed", "xenopus oocytes has allowed their", "oocytes has allowed their transport", "has allowed their transport properties", "allowed their transport properties to", "their transport properties to be", "transport properties to be determined.", "to be determined. slc28a1", "be determined. slc28a1 mediates", "determined. slc28a1 mediates the", "slc28a1 mediates the uptake of", "mediates the uptake of pyrimidine", "the uptake of pyrimidine nucleosides", "uptake of pyrimidine nucleosides and", "of pyrimidine nucleosides and adenosine", "nucleosides and adenosine ritzel", "and adenosine ritzel et", "adenosine ritzel et al.", "al. 1997 slc28a2", "1997 slc28a2 the", "slc28a2 the uptake of purine", "the uptake of purine nucleosides", "uptake of purine nucleosides and", "of purine nucleosides and uridine", "nucleosides and uridine wang", "and uridine wang et", "uridine wang et al.", "al. 1997 and", "1997 and slc28a3", "and slc28a3 the uptake of", "slc28a3 the uptake of purine", "the uptake of purine and", "uptake of purine and pyrimidine", "of purine and pyrimidine nucleosides", "and pyrimidine nucleosides ritzel", "pyrimidine nucleosides ritzel et", "nucleosides ritzel et al.", "ritzel et al. 2001 .", "al. 2001 . amino", "2001 . amino acid", ". amino acid sequence", "amino acid sequence motifs that", "acid sequence motifs that determine", "sequence motifs that determine the", "motifs that determine the specificities", "that determine the specificities of", "determine the specificities of these", "the specificities of these transporters", "specificities of these transporters have", "of these transporters have been", "these transporters have been identified", "transporters have been identified in", "have been identified in studies", "been identified in studies of", "identified in studies of chimeric", "in studies of chimeric and", "studies of chimeric and mutant", "of chimeric and mutant proteins", "and mutant proteins loewen", "mutant proteins loewen et", "proteins loewen et al.", "loewen et al. 1999 .", "al. 1999 . slc28a3", "1999 . slc28a3 protein", ". slc28a3 protein co", "slc28a3 protein co transports two", "protein co transports two sodium", "co transports two sodium ions", "transports two sodium ions per", "two sodium ions per nucleoside", "ions per nucleoside slc28a1", "per nucleoside slc28a1 and", "nucleoside slc28a1 and 2", "slc28a1 and 2 transport one", "and 2 transport one sodium", "2 transport one sodium per", "transport one sodium per nucleoside", "sodium per nucleoside ritzel", "per nucleoside ritzel et", "nucleoside ritzel et al.", "ritzel et al. 2001 .

physiological", "et al. 2001 .

physiological roles", "al. 2001 .

physiological roles for", "2001 .

physiological roles for nucleoside", ".

physiological roles for nucleoside and", "roles for nucleoside and base", "for nucleoside and base transport", "nucleoside and base transport include", "and base transport include provision", "base transport include provision of", "transport include provision of nucleosides", "include provision of nucleosides to", "provision of nucleosides to cells", "of nucleosides to cells with", "nucleosides to cells with little", "to cells with little capacity", "cells with little capacity to", "with little capacity to synthesize", "little capacity to synthesize these", "capacity to synthesize these molecules", "to synthesize these molecules de", "synthesize these molecules de novo", "molecules de novo and", "de novo and regulation", "novo and regulation of", "and regulation of extracellular levels", "regulation of extracellular levels of", "of extracellular levels of adenosine", "levels of adenosine which", "of adenosine which is", "adenosine which is released", "which is released from muscle", "is released from muscle during", "released from muscle during intense", "from muscle during intense exercise", "muscle during intense exercise and", "during intense exercise and has", "intense exercise and has signaling", "exercise and has signaling properties.", "has signaling properties. in", "signaling properties. in kidney", "properties. in kidney and", "in kidney and intestinal epithelia", "and intestinal epithelia the", "intestinal epithelia the combination", "epithelia the combination of", "the combination of apically localized", "combination of apically localized cnt", "of apically localized cnt transporters", "apically localized cnt transporters and", "localized cnt transporters and basolaterally", "cnt transporters and basolaterally localized", "transporters and basolaterally localized ent", "and basolaterally localized ent transporters", "basolaterally localized ent transporters provides", "localized ent transporters provides a", "ent transporters provides a mechanism", "transporters provides a mechanism for", "provides a mechanism for net", "a mechanism for net transport", "mechanism for net transport of", "for net transport of nucleosides", "transport of nucleosides mangravite", "of nucleosides mangravite et", "nucleosides mangravite et al.", "mangravite et al. 2003 .", "al. 2003 . these", "2003 . these transporters", ". these transporters also", "these transporters also mediate the", "transporters also mediate the uptake", "also mediate the uptake of", "mediate the uptake of nucleoside", "the uptake of nucleoside analogs", "uptake of nucleoside analogs used", "of nucleoside analogs used clinically", "nucleoside analogs used clinically as", "analogs used clinically as anti", "used clinically as anti viral", "clinically as anti viral and", "as anti viral and anti", "anti viral and anti tumor", "viral and anti tumor drugs.

orthologs", "and anti tumor drugs.

orthologs of", "anti tumor drugs.

orthologs of human", "tumor drugs.

orthologs of human concentrative", "drugs.

orthologs of human concentrative and", "of human concentrative and equilibrative", "human concentrative and equilibrative transporter", "concentrative and equilibrative transporter proteins", "and equilibrative transporter proteins have", "equilibrative transporter proteins have been", "transporter proteins have been identified", "proteins have been identified in", "have been identified in many", "been identified in many eukaryotes", "in many eukaryotes but", "many eukaryotes but functional", "eukaryotes but functional studies", "but functional studies of transporters", "functional studies of transporters even", "studies of transporters even from", "of transporters even from organisms", "transporters even from organisms closely", "even from organisms closely related", "from organisms closely related to", "organisms closely related to humans", "related to humans e.g.", "to humans e.g. rat", "e.g. rat gerstin et", "rat gerstin et al.", "et al. 2002 have", "al. 2002 have revealed", "2002 have revealed differences", "have revealed differences in substrate", "revealed differences in substrate specificities.", "in substrate specificities. prediction", "substrate specificities. prediction of", "specificities. prediction of drug", "prediction of drug uptake and", "of drug uptake and other", "drug uptake and other functions", "uptake and other functions of", "and other functions of these", "other functions of these molecules", "functions of these molecules by", "of these molecules by human", "by human model", "human model organism", "model organism orthology is thus", "organism orthology is thus risky." ] }, { "record_id": "GLY_000594_1_604", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "844615", "r hsa", "hsa 844615", "r hsa 844615" ] }, { "record_id": "GLY_000594_1_604", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "the aim2", "aim2 inflammasome", "the aim2 inflammasome", "aim2 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ko", "and salm5 ko et", "salm5 ko et al.", "2006 wang et al.2006", "wang et al.2006 morimura", "et al.2006 morimura et", "al.2006 morimura et al.", "morimura et al. 2006 ." ] }, { "record_id": "GLY_000594_1_610", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8851680", "r hsa", "hsa 8851680", "r hsa 8851680" ] }, { "record_id": "GLY_000594_1_610", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "family interactions", "butyrophilin btn", "btn family", "btn family interactions", "butyrophilin btn family", "and butyrophilin", "butyrophilin like", "molecules are", "are regulators", "regulators of", "of immune", "immune responses", "responses that", "that belong", "belong to", "to the", "the immunoglobulin", "superfamily of", "of transmembrane", "transmembrane proteins.", "proteins. they", "they are", "are structurally", "structurally related", "related to", "the b7", "b7 family", "family of", "of 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the", "
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the", ".
the human", "
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the", "2014 .
the human", ".
the human butyrophilin", "
the human butyrophilin family", "human butyrophilin family includes", "butyrophilin family includes seven", "family includes seven members", "includes seven members that", "seven members that are", "members that are subdivided", "that are subdivided into", "are subdivided into three", "subdivided into three subfamilies:", "into three subfamilies: btn1", "subfamilies: btn1 btn2", "btn1 btn2 and", "btn2 and btn3. the", "and btn3. the btn1", "btn3. the btn1 subfamily", "the btn1 subfamily contains", "btn1 subfamily contains only", "subfamily contains only the", "contains only the prototypic", "only the prototypic single", "the prototypic single copy", "prototypic single copy btn1a1", "single copy btn1a1 gene", "btn1a1 gene whereas", "gene whereas the", "whereas the btn2 and", "the btn2 and btn3", "btn2 and btn3 subfamilies", "and btn3 subfamilies each", "btn3 subfamilies each contain", "subfamilies each contain three", "each contain three genes", "contain three genes btn2a1", "genes 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"as regulators of immune", "regulators of immune responses.", "of immune responses. btnl", "immune responses. btnl proteins", "responses. btnl proteins share", "btnl proteins share considerable", "proteins share considerable homology", "share considerable homology to", "considerable homology to the", "homology to the btn", "to the btn family", "the btn family members.", "btn family members. the", "family members. the human", "members. the human genome", "the human genome contains", "human genome contains four", "genome contains four btnl", "contains four btnl genes:", "four btnl genes: btnl2", "genes: btnl2 3", "3 8 and", "and 9 abeler", "9 abeler domer", "butyrophilins btns and", "btns and butyrophilin like", "and butyrophilin like btnl", "like btnl molecules", "btnl molecules are regulators", "molecules are regulators of immune", "are regulators of immune responses", "regulators of immune responses that", "of immune responses that belong", "immune responses that belong to", "responses that belong to the", "that belong to the immunoglobulin", "to the immunoglobulin ig", "immunoglobulin ig superfamily", "ig superfamily of transmembrane", "superfamily of transmembrane proteins. they", "of transmembrane proteins. they are", "transmembrane proteins. they are structurally", "proteins. they are structurally related", "they are structurally related to", "are structurally related to the", "structurally related to the b7", "related to the b7 family", "to the b7 family of", "the b7 family of co", "b7 family of co stimulatory", "family of co stimulatory molecules", "of co stimulatory molecules and", "co stimulatory molecules and have", "stimulatory molecules and have similar", "molecules and have similar immunomodulatory", "and have similar immunomodulatory functions", "similar immunomodulatory functions afrache", "immunomodulatory functions afrache et", "functions afrache et al.", "et al. 2012 arnett", "al. 2012 arnett &", "2012 arnett & viney", "arnett & viney 2014 .", "& viney 2014 . btns", "viney 2014 . btns are", "2014 . btns are implicated", ". btns are implicated in", "btns are implicated in t", "are implicated in t cell", "implicated in t cell development", "t cell development activation", "cell development activation and", "development activation and inhibition", "activation and inhibition as", "and inhibition as well", "inhibition as well as", "as well as in the", "well as in the modulation", "as in the modulation of", "in the modulation of the", "the modulation of the interactions", "modulation of the interactions of", "of the interactions of t", "the interactions of t cells", "interactions of t cells with", "of t cells with antigen", "t cells with antigen presenting", "cells with antigen presenting cells", "with antigen presenting cells and", "antigen presenting cells and epithelial", "presenting cells and epithelial cells.", "cells and epithelial cells. certain", "and epithelial cells. certain btnsare", "epithelial cells. certain btnsare genetically", "cells. certain btnsare genetically associated", "certain btnsare genetically associated with", "btnsare genetically associated with autoimmune", "genetically associated with autoimmune and", "associated with autoimmune and inflammatory", "with autoimmune and inflammatory diseases", "and inflammatory diseases abeler", "inflammatory diseases abeler domer", "diseases abeler domer et", "abeler domer et al. 2014", "domer et al. 2014 .", "et al. 2014 .
the", "al. 2014 .
the human", "2014 .
the human butyrophilin", ".
the human butyrophilin family", "
the human butyrophilin family includes", "human butyrophilin family includes seven", "butyrophilin family includes seven members", "family includes seven members that", "includes seven members that are", "seven members that are subdivided", "members that are subdivided into", "that are subdivided into three", "are subdivided into three subfamilies:", "subdivided into three subfamilies: btn1", "three subfamilies: btn1 btn2", "subfamilies: btn1 btn2 and", "btn1 btn2 and btn3.", "btn2 and btn3. the btn1", "and btn3. the btn1 subfamily", "btn3. the btn1 subfamily contains", "the btn1 subfamily contains only", "btn1 subfamily contains only the", "subfamily contains only the prototypic", "contains only the prototypic single", "only the prototypic single copy", "the prototypic single copy btn1a1", "prototypic single copy btn1a1 gene", "copy btn1a1 gene whereas", "btn1a1 gene whereas the", "gene whereas the btn2", "whereas the btn2 and btn3", "the btn2 and btn3 subfamilies", "btn2 and btn3 subfamilies each", "and btn3 subfamilies each contain", "btn3 subfamilies each contain three", "subfamilies each contain three genes", "each contain three genes btn2a1", "three genes btn2a1 btn2a2", "genes btn2a1 btn2a2 and", "btn2a1 btn2a2 and btn2a3", "btn2a2 and btn2a3 and", "and btn2a3 and btn3a1", "and btn3a1 btn3a2 and", "btn3a1 btn3a2 and btn3a3", "btn3a2 and btn3a3 respectively", "btn3a3 respectively note", "respectively note that btn2a3", "note that btn2a3 is a", "that btn2a3 is a pseudogene", "btn2a3 is a pseudogene .", "is a pseudogene . btn1a1", "a pseudogene . btn1a1 has", "pseudogene . btn1a1 has a", ". btn1a1 has a crucial", "btn1a1 has a crucial function", "has a crucial function in", "a crucial function in the", "crucial function in the secretion", "function in the secretion of", "in the secretion of lipids", "the secretion of lipids into", "secretion of lipids into milk", "lipids into milk ogg", "into milk ogg et", "milk ogg et al.", "et al. 2004 and", "al. 2004 and collectively", "and collectively btn2 and", "collectively btn2 and btn3", "btn2 and btn3 proteins are", "and btn3 proteins are cell", "btn3 proteins are cell surface", "proteins are cell surface transmembrane", "are cell surface transmembrane glycoproteins", "surface transmembrane glycoproteins that", "transmembrane glycoproteins that act", "glycoproteins that act as", "that act as regulators of", "act as regulators of immune", "as regulators of immune responses.", "regulators of immune responses. btnl", "of immune responses. btnl proteins", "immune responses. btnl proteins share", "responses. btnl proteins share considerable", "btnl proteins share considerable homology", "proteins share considerable homology to", "share considerable homology to the", "considerable homology to the btn", "homology to the btn family", "to the btn family members.", "the btn family members. the", "btn family members. the human", "family members. the human genome", "members. the human genome contains", "the human genome contains four", "human genome contains four btnl", "genome contains four btnl genes:", "contains four btnl genes: btnl2", "btnl genes: btnl2 3", "btnl2 3 8", "3 8 and 9", "8 and 9 abeler", "and 9 abeler domer", "9 abeler domer et" ] }, { "record_id": "GLY_000594_1_611", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8852276", "r hsa", "hsa 8852276", "r hsa 8852276" ] }, { "record_id": "GLY_000594_1_611", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "the role", "role of", "of gtse1", "gtse1 in", "in g2/m", "g2/m progression", "progression after", "after g2", "g2 checkpoint", "the role of", "role of gtse1", "of gtse1 in", "gtse1 in g2/m", "in g2/m progression", "g2/m progression after", "progression after g2", "after g2 checkpoint", "the role of gtse1", "role of gtse1 in", "of gtse1 in g2/m", "gtse1 in g2/m progression", "in g2/m progression after", "g2/m progression after g2", 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"a role", "role in", "checkpoint recovery", "recovery after", "after dna", "damage but", "but is", "is not", "not transcriptionally", "transcriptionally regulated", "regulated by", "by tp53", "monte et", "al. 2003", "al. 2004", "scolz et", "al. 2012", "2012 .

in", ".

in g1", "g1 cells", "gtse1 is", "is found", "found at", "at the", "the microtubule", "microtubule lattice", "likely due", "due to", "to direct", "direct binding", "binding to", "to tubulin.", "tubulin. an", "an evolutionarily", "evolutionarily conserved", "conserved interaction", "interaction between", "between gtse1", "gtse1 and", "and mapre1", "microtubule plus", "plus end", "end protein", "promotes gtse1", "gtse1 localization", "localization to", "the growing", "growing tip", "tip of", "the microtubules", "which contributes", "contributes to", "to cell", "cell migration", "migration and", "and is", "is likely", "likely involved", "involved in", "in cancer", "cancer cell", "cell invasiveness.", "invasiveness. highly", "highly invasive", "invasive breast", "breast cancer", "cell lines", "lines exhibit", "exhibit high", "high gtse1", "gtse1 levels", "in g1", "while gtse1", "g1 are", "are normally", "normally low.", "low. at", "the beginning", "beginning of", "of mitotic", "mitotic prometaphase", "is phosphorylated", "phosphorylated by", "by mitotic", "mitotic kinase", "kinase s", "possibly cdk1", "in proximity", "proximity to", "the mapre1", "mapre1 binding", "binding region", "causing gtse1", "gtse1 dissociation", "dissociation from", "from the", "the plus", "end microtubule", "microtubule ends", "2012 .

during", ".

during g2", "cycle re", "re entry", "entry after", "damage induced", "induced g2", "g2 arrest", "gtse1 relocates", "relocates to", "the nucleus", "nucleus where", "where it", "it binds", "binds tp53", "tp53 and", "in an", "an mdm2", "mdm2 dependent", "dependent manner", "promotes tp53", "tp53 cytoplasmic", "cytoplasmic translocation", "translocation and", "and proteasome", "proteasome mediated", "mediated degradation", "2004 .", ". relocation", "relocation of", "gtse1 to", "nucleus in", "g2 phase", "phase depends", "depends on", "on plk1", "plk1 mediated", "mediated phosphorylation", "phosphorylation of", "liu et", "al. 2010", "2010 .

gtse1", ".

gtse1 facilitated", "facilitated down", "down regulation", "regulation of", "tp53 in", "g2 allows", "allows cells", "cells to", "to avoid", "avoid tp53", "tp53 mediated", "mediated apoptosis", "apoptosis upon", "upon dna", "damage and", "and to", "to re", "re enter", "enter cell", "2003 .", ". while", "while tp53", "tp53 down", "regulation mediated", "mediated by", "by gtse1", "g2 correlates", "correlates with", "with decreased", "decreased expression", "expression of", "tp53 target", "target genes", "genes involved", "in apoptosis", "apoptosis and", "and cell", "cycle arrest", "gtse1 can", "can also", "also increase", "increase the", "the half", "half life", "life of", "the tp53", "target p21", "cdkn1a .", ". gtse1", "gtse1 mediated", "mediated stabilization", "stabilization of", "of cdkn1a", "cdkn1a involves", "involves interaction", "interaction of", "gtse1 with", "with cdkn1a", "cdkn1a and", "and its", "its chaperone", "chaperone complex", "consisting of", "of hsp90", "hsp90 and", "and fkbpl", "and may", "may be", "be involved", "in resistance", "resistance to", "to paclitaxel", "paclitaxel treatment", "bublik et", "2010 .", "gtse1 b99", "b99 was", "was identified as", "identified as a", "as a microtubule", "a microtubule associated", "microtubule associated protein", "associated protein product", "protein product of", "product of the", "of the mouse", "the mouse b99", "mouse b99 gene", "gene which", "which exhibits both", "exhibits both a", "both a cell", "a cell cycle", "cell cycle regulated", "cycle regulated expression", "with highest levels", "highest levels in", "levels in g2", "and dna damage", "dna damage triggered", "damage triggered expression", "triggered expression under", "expression under direct", "under direct control", "direct control of", "control of tp53", "tp53 p53", "utrera et al.", "et al. 1998", "1998 collavin", "collavin et al.", "et al. 2000", "al. 2000 .", "2000 . human", ". human gtse1", "gtse1 similar", "similar to the", "to the mouse", "the mouse counterpart", "counterpart binds", "binds to microtubules", "microtubules shows", "shows cell cycle", "regulated expression with", "expression with a", "with a peak", "a peak in", "peak in g2", "in g2 and", "g2 and plays", "and plays a", "plays a role", "a role in", "role in g2", "in g2 checkpoint", "g2 checkpoint recovery", "checkpoint recovery after", "recovery after dna", "after dna damage", "dna damage but", "damage but is", "but is not", "is not transcriptionally", "not transcriptionally regulated", "transcriptionally regulated by", "regulated by tp53", "tp53 monte", "monte et al.", "et al. 2003", "2003 monte", "et al. 2004", "2004 scolz", "scolz et al.", "et al. 2012", "al. 2012 .

in", "2012 .

in g1", ".

in g1 cells", "cells gtse1", "gtse1 is found", "is found at", "found at the", "at the microtubule", "the microtubule lattice", "lattice likely", "likely due to", "due to direct", "to direct binding", "direct binding to", "binding to tubulin.", "to tubulin. an", "tubulin. an evolutionarily", "an evolutionarily conserved", "evolutionarily conserved interaction", "conserved interaction between", "interaction between gtse1", "between gtse1 and", "gtse1 and mapre1", "mapre1 eb1", "a microtubule plus", "microtubule plus end", "plus end protein", "protein promotes", "promotes gtse1 localization", "gtse1 localization to", "localization to the", "to the growing", "the growing tip", "growing tip of", "tip of the", "of the microtubules", "microtubules which", "which contributes to", "contributes to cell", "to cell migration", "cell migration and", "migration and is", "and is likely", "is likely involved", "likely involved in", "involved in cancer", "in cancer cell", "cancer cell invasiveness.", "cell invasiveness. highly", "invasiveness. highly invasive", "highly invasive breast", "invasive breast cancer", "breast cancer cell", "cancer cell lines", "cell lines exhibit", "lines exhibit high", "exhibit high gtse1", "high gtse1 levels", "gtse1 levels in", "levels in g1", "g1 while", "while gtse1 levels", "in g1 are", "g1 are normally", "are normally low.", "normally low. at", "low. at the", "at the beginning", "the beginning of", "beginning of mitotic", "of mitotic prometaphase", "prometaphase gtse1", "gtse1 is phosphorylated", "is phosphorylated by", "phosphorylated by mitotic", "by mitotic kinase", "mitotic kinase s", "cdk1 in", "in proximity to", "proximity to the", "to the mapre1", "the mapre1 binding", "mapre1 binding region", "region causing", "causing gtse1 dissociation", "gtse1 dissociation from", "dissociation from the", "from the plus", "the plus end", "plus end microtubule", "end microtubule ends", "ends scolz", "al. 2012 .

during", "2012 .

during g2", ".

during g2 checkpoint", "recovery cell", "cell cycle re", "cycle re entry", "re entry after", "entry after dna", "dna damage induced", "damage induced g2", "induced g2 arrest", "gtse1 relocates to", "relocates to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it binds", "it binds tp53", "binds tp53 and", "and in", "in an mdm2", "an mdm2 dependent", "mdm2 dependent manner", "manner promotes", "promotes tp53 cytoplasmic", "tp53 cytoplasmic translocation", "cytoplasmic translocation and", "translocation and proteasome", "and proteasome mediated", "proteasome mediated degradation", "degradation monte", "al. 2004 .", "2004 . relocation", ". relocation of", "relocation of gtse1", "of gtse1 to", "gtse1 to the", "the nucleus in", "nucleus in g2", "in g2 phase", "g2 phase depends", "phase depends on", "depends on plk1", "on plk1 mediated", "plk1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of gtse1", "gtse1 liu", "liu et al.", "et al. 2010", "al. 2010 .

gtse1", "2010 .

gtse1 facilitated", ".

gtse1 facilitated down", "facilitated down regulation", "down regulation of", "regulation of tp53", "of tp53 in", "tp53 in g2", "in g2 allows", "g2 allows cells", "allows cells to", "cells to avoid", "to avoid tp53", "avoid tp53 mediated", "tp53 mediated apoptosis", "mediated apoptosis upon", "apoptosis upon dna", "upon dna damage", "dna damage and", "damage and to", "and to re", "to re enter", "re enter cell", "enter cell cycle", "cycle monte", "al. 2003 .", "2003 . while", ". while tp53", "while tp53 down", "tp53 down regulation", "down regulation mediated", "regulation mediated by", "mediated by gtse1", "by gtse1 in", "gtse1 in g2", "in g2 correlates", "g2 correlates with", "correlates with decreased", "with decreased expression", "decreased expression of", "expression of tp53", "of tp53 target", "tp53 target genes", "target genes involved", "genes involved in", "involved in apoptosis", "in apoptosis and", "apoptosis and cell", "and cell cycle", "cell cycle arrest", "arrest gtse1", "gtse1 can also", "can also increase", "also increase the", "increase the half", "the half life", "half life of", "life of the", "of the tp53", "the tp53 target", "tp53 target p21", "p21 cdkn1a", "cdkn1a . gtse1", ". gtse1 mediated", "gtse1 mediated stabilization", "mediated stabilization of", "stabilization of cdkn1a", "of cdkn1a involves", "cdkn1a involves interaction", "involves interaction of", "interaction of gtse1", "of gtse1 with", "gtse1 with cdkn1a", "with cdkn1a and", "cdkn1a and its", "and its chaperone", "its chaperone complex", "complex consisting", "consisting of hsp90", "of hsp90 and", "hsp90 and fkbpl", "fkbpl wisp39", "and may be", "may be involved", "be involved in", "involved in resistance", "in resistance to", "resistance to paclitaxel", "to paclitaxel treatment", "treatment bublik", "bublik et al.", "al. 2010 .", "b99 was identified", "was identified as a", "identified as a microtubule", "as a microtubule associated", "a microtubule associated protein", "microtubule associated protein product", "associated protein product of", "protein product of the", "product of the mouse", "of the mouse b99", "the mouse b99 gene", "b99 gene which", "gene which exhibits", "which exhibits both a", "exhibits both a cell", "both a cell cycle", "a cell cycle regulated", "cell cycle regulated expression", "expression with highest", "with highest levels in", "highest levels in g2", "g2 and dna", "and dna damage triggered", "dna damage triggered expression", "damage triggered expression under", "triggered expression under direct", "expression under direct control", "under direct control of", "direct control of tp53", "of tp53 p53", "p53 utrera", "utrera et al. 1998", "al. 1998 collavin", "1998 collavin et", "collavin et al. 2000", "et al. 2000 .", "al. 2000 . human", "2000 . human gtse1", "human gtse1 similar", "gtse1 similar to", "similar to the mouse", "to the mouse counterpart", "mouse counterpart binds", "counterpart binds to", "to microtubules shows", "microtubules shows cell", "shows cell cycle regulated", "cycle regulated expression with", "regulated expression with a", "expression with a peak", "with a peak in", "a peak in g2", "peak in g2 and", "in g2 and plays", "g2 and plays a", "and plays a role", "plays a role in", "a role in g2", "role in g2 checkpoint", "in g2 checkpoint recovery", "g2 checkpoint recovery after", "checkpoint recovery after dna", "recovery after dna damage", "after dna damage but", "dna damage but is", "damage but is not", "but is not transcriptionally", "is not transcriptionally regulated", "not transcriptionally regulated by", "transcriptionally regulated by tp53", "by tp53 monte", "tp53 monte et", "monte et al. 2003", "al. 2003 monte", "2003 monte et", "monte et al. 2004", "al. 2004 scolz", "2004 scolz et", "scolz et al. 2012", "et al. 2012 .

in", "al. 2012 .

in g1", "2012 .

in g1 cells", "g1 cells gtse1", "cells gtse1 is", "gtse1 is found at", "is found at the", "found at the microtubule", "at the microtubule lattice", "microtubule lattice likely", "lattice likely due", "likely due to direct", "due to direct binding", "to direct binding to", "direct binding to tubulin.", "binding to tubulin. an", "to tubulin. an evolutionarily", "tubulin. an evolutionarily conserved", "an evolutionarily conserved interaction", "evolutionarily conserved interaction between", "conserved interaction between gtse1", "interaction between gtse1 and", "between gtse1 and mapre1", "and mapre1 eb1", "eb1 a", "a microtubule plus end", "microtubule plus end protein", "end protein promotes", "protein promotes gtse1", "promotes gtse1 localization to", "gtse1 localization to the", "localization to the growing", "to the growing tip", "the growing tip of", "growing tip of the", "tip of the microtubules", "the microtubules which", "microtubules which contributes", "which contributes to cell", "contributes to cell migration", "to cell migration and", "cell migration and is", "migration and is likely", "and is likely involved", "is likely involved in", "likely involved in cancer", "involved in cancer cell", "in cancer cell invasiveness.", "cancer cell invasiveness. highly", "cell invasiveness. highly invasive", "invasiveness. highly invasive breast", "highly invasive breast cancer", "invasive breast cancer cell", "breast cancer cell lines", "cancer cell lines exhibit", "cell lines exhibit high", "lines exhibit high gtse1", "exhibit high gtse1 levels", "high gtse1 levels in", "gtse1 levels in g1", "in g1 while", "g1 while gtse1", "while gtse1 levels in", "levels in g1 are", "in g1 are normally", "g1 are normally low.", "are normally low. at", "normally low. at the", "low. at the beginning", "at the beginning of", "the beginning of mitotic", "beginning of mitotic prometaphase", "mitotic prometaphase gtse1", "prometaphase gtse1 is", "gtse1 is phosphorylated by", "is phosphorylated by mitotic", "phosphorylated by mitotic kinase", "by mitotic kinase s", "s possibly", "possibly cdk1 in", "cdk1 in proximity", "in proximity to the", "proximity to the mapre1", "to the mapre1 binding", "the mapre1 binding region", "binding region causing", "region causing gtse1", "causing gtse1 dissociation from", "gtse1 dissociation from the", "dissociation from the plus", "from the plus end", "the plus end microtubule", "plus end microtubule ends", "microtubule ends scolz", "ends scolz et", "et al. 2012 .

during", "al. 2012 .

during g2", "2012 .

during g2 checkpoint", ".

during g2 checkpoint recovery", "checkpoint recovery cell", "recovery cell cycle", "cell cycle re entry", "cycle re entry after", "re entry after dna", "entry after dna damage", "after dna damage induced", "dna damage induced g2", "damage induced g2 arrest", "gtse1 relocates to the", "relocates to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it binds", "where it binds tp53", "it binds tp53 and", "tp53 and in", "and in an", "in an mdm2 dependent", "an mdm2 dependent manner", "dependent manner promotes", "manner promotes tp53", "promotes tp53 cytoplasmic translocation", "tp53 cytoplasmic translocation and", "cytoplasmic translocation and proteasome", "translocation and proteasome mediated", "and proteasome mediated degradation", "mediated degradation monte", "degradation monte et", "et al. 2004 .", "al. 2004 . relocation", "2004 . relocation of", ". relocation of gtse1", "relocation of gtse1 to", "of gtse1 to the", "gtse1 to the nucleus", "to the nucleus in", "the nucleus in g2", "nucleus in g2 phase", "in g2 phase depends", "g2 phase depends on", "phase depends on plk1", "depends on plk1 mediated", "on plk1 mediated phosphorylation", "plk1 mediated phosphorylation of", "mediated phosphorylation of gtse1", "of gtse1 liu", "gtse1 liu et", "liu et al. 2010", "et al. 2010 .

gtse1", "al. 2010 .

gtse1 facilitated", "2010 .

gtse1 facilitated down", ".

gtse1 facilitated down regulation", "facilitated down regulation of", "down regulation of tp53", "regulation of tp53 in", "of tp53 in g2", "tp53 in g2 allows", "in g2 allows cells", "g2 allows cells to", "allows cells to avoid", "cells to avoid tp53", "to avoid tp53 mediated", "avoid tp53 mediated apoptosis", "tp53 mediated apoptosis upon", "mediated apoptosis upon dna", "apoptosis upon dna damage", "upon dna damage and", "dna damage and to", "damage and to re", "and to re enter", "to re enter cell", "re enter cell cycle", "cell cycle monte", "cycle monte et", "et al. 2003 .", "al. 2003 . while", "2003 . while tp53", ". while tp53 down", "while tp53 down regulation", "tp53 down regulation mediated", "down regulation mediated by", "regulation mediated by gtse1", "mediated by gtse1 in", "by gtse1 in g2", "gtse1 in g2 correlates", "in g2 correlates with", "g2 correlates with decreased", "correlates with decreased expression", "with decreased expression of", "decreased expression of tp53", "expression of tp53 target", "of tp53 target genes", "tp53 target genes involved", "target genes involved in", "genes involved in apoptosis", "involved in apoptosis and", "in apoptosis and cell", "apoptosis and cell cycle", "and cell cycle arrest", "cycle arrest gtse1", "arrest gtse1 can", "gtse1 can also increase", "can also increase the", "also increase the half", "increase the half life", "the half life of", "half life of the", "life of the tp53", "of the tp53 target", "the tp53 target p21", "target p21 cdkn1a", "p21 cdkn1a .", "cdkn1a . gtse1 mediated", ". gtse1 mediated stabilization", "gtse1 mediated stabilization of", "mediated stabilization of cdkn1a", "stabilization of cdkn1a involves", "of cdkn1a involves interaction", "cdkn1a involves interaction of", "involves interaction of gtse1", "interaction of gtse1 with", "of gtse1 with cdkn1a", "gtse1 with cdkn1a and", "with cdkn1a and its", "cdkn1a and its chaperone", "and its chaperone complex", "chaperone complex consisting", "complex consisting of", "consisting of hsp90 and", "of hsp90 and fkbpl", "and fkbpl wisp39", "wisp39 and", "and may be involved", "may be involved in", "be involved in resistance", "involved in resistance to", "in resistance to paclitaxel", "resistance to paclitaxel treatment", "paclitaxel treatment bublik", "treatment bublik et", "bublik et al. 2010", "et al. 2010 .", "gtse1 b99 was", "b99 was identified as", "was identified as a microtubule", "identified as a microtubule associated", "as a microtubule associated protein", "a microtubule associated protein product", "microtubule associated protein product of", "associated protein product of the", "protein product of the mouse", "product of the mouse b99", "of the mouse b99 gene", "mouse b99 gene which", "b99 gene which exhibits", "gene which exhibits both", "which exhibits both a cell", "exhibits both a cell cycle", "both a cell cycle regulated", "a cell cycle regulated expression", "regulated expression with highest", "expression with highest levels", "with highest levels in g2", "levels in g2 and", "in g2 and dna", "g2 and dna damage", "and dna damage triggered expression", "dna damage triggered expression under", "damage triggered expression under direct", "triggered expression under direct control", "expression under direct control of", "under direct control of tp53", "control of tp53 p53", "p53 utrera et", "et al. 1998 collavin", "al. 1998 collavin et", "1998 collavin et al.", "collavin et al. 2000 .", "et al. 2000 . human", "al. 2000 . human gtse1", ". human gtse1 similar", "human gtse1 similar to", "gtse1 similar to the", "similar to the mouse counterpart", "the mouse counterpart binds", "mouse counterpart binds to", "counterpart binds to microtubules", "binds to microtubules shows", "to microtubules shows cell", "microtubules shows cell cycle", "shows cell cycle regulated expression", "cell cycle regulated expression with", "cycle regulated expression with a", "regulated expression with a peak", "expression with a peak in", "with a peak in g2", "a peak in g2 and", "peak in g2 and plays", "in g2 and plays a", "g2 and plays a role", "and plays a role in", "plays a role in g2", "a role in g2 checkpoint", "role in g2 checkpoint recovery", "in g2 checkpoint recovery after", "g2 checkpoint recovery after dna", "checkpoint recovery after dna damage", "recovery after dna damage but", "after dna damage but is", "dna damage but is not", "damage but is not transcriptionally", "but is not transcriptionally regulated", "is not transcriptionally regulated by", "not transcriptionally regulated by tp53", "regulated by tp53 monte", "by tp53 monte et", "tp53 monte et al.", "et al. 2003 monte", "al. 2003 monte et", "2003 monte et al.", "et al. 2004 scolz", "al. 2004 scolz et", "2004 scolz et al.", "scolz et al. 2012 .

in", "et al. 2012 .

in g1", "al. 2012 .

in g1 cells", ".

in g1 cells gtse1", "g1 cells gtse1 is", "cells gtse1 is found", "gtse1 is found at the", "is found at the microtubule", "found at the microtubule lattice", "the microtubule lattice likely", "microtubule lattice likely due", "lattice likely due to", "likely due to direct binding", "due to direct binding to", "to direct binding to tubulin.", "direct binding to tubulin. an", "binding to tubulin. an evolutionarily", "to tubulin. an evolutionarily conserved", "tubulin. an evolutionarily conserved interaction", "an evolutionarily conserved interaction between", "evolutionarily conserved interaction between gtse1", "conserved interaction between gtse1 and", "interaction between gtse1 and mapre1", "gtse1 and mapre1 eb1", "eb1 a microtubule", "a microtubule plus end protein", "plus end protein promotes", "end protein promotes gtse1", "protein promotes gtse1 localization", "promotes gtse1 localization to the", "gtse1 localization to the growing", "localization to the growing tip", "to the growing tip of", "the growing tip of the", "growing tip of the microtubules", "of the microtubules which", "the microtubules which contributes", "microtubules which contributes to", "which contributes to cell migration", "contributes to cell migration and", "to cell migration and is", "cell migration and is likely", "migration and is likely involved", "and is likely involved in", "is likely involved in cancer", "likely involved in cancer cell", "involved in cancer cell invasiveness.", "in cancer cell invasiveness. highly", "cancer cell invasiveness. highly invasive", "cell invasiveness. highly invasive breast", "invasiveness. highly invasive breast cancer", "highly invasive breast cancer cell", "invasive breast cancer cell lines", "breast cancer cell lines exhibit", "cancer cell lines exhibit high", "cell lines exhibit high gtse1", "lines exhibit high gtse1 levels", "exhibit high gtse1 levels in", "high gtse1 levels in g1", "levels in g1 while", "in g1 while gtse1", "g1 while gtse1 levels", "while gtse1 levels in g1", "gtse1 levels in g1 are", "levels in g1 are normally", "in g1 are normally low.", "g1 are normally low. at", "are normally low. at the", "normally low. at the beginning", "low. at the beginning of", "at the beginning of mitotic", "the beginning of mitotic prometaphase", "of mitotic prometaphase gtse1", "mitotic prometaphase gtse1 is", "prometaphase gtse1 is phosphorylated", "gtse1 is phosphorylated by mitotic", "is phosphorylated by mitotic kinase", "phosphorylated by mitotic kinase s", "kinase s possibly", "s possibly cdk1", "possibly cdk1 in proximity", "cdk1 in proximity to", "in proximity to the mapre1", "proximity to the mapre1 binding", "to the mapre1 binding region", "mapre1 binding region causing", "binding region causing gtse1", "region causing gtse1 dissociation", "causing gtse1 dissociation from the", "gtse1 dissociation from the plus", "dissociation from the plus end", "from the plus end microtubule", "the plus end microtubule ends", "end microtubule ends scolz", "microtubule ends scolz et", "ends scolz et al.", "scolz et al. 2012 .

during", "et al. 2012 .

during g2", "al. 2012 .

during g2 checkpoint", "2012 .

during g2 checkpoint recovery", "g2 checkpoint recovery cell", "checkpoint recovery cell cycle", "recovery cell cycle re", "cell cycle re entry after", "cycle re entry after dna", "re entry after dna damage", "entry after dna damage induced", "after dna damage induced g2", "dna damage induced g2 arrest", "g2 arrest gtse1", "arrest gtse1 relocates", "gtse1 relocates to the nucleus", "relocates to the nucleus where", "to the nucleus where it", "the nucleus where it binds", "nucleus where it binds tp53", "where it binds tp53 and", "binds tp53 and in", "tp53 and in an", "and in an mdm2", "in an mdm2 dependent manner", "mdm2 dependent manner promotes", "dependent manner promotes tp53", "manner promotes tp53 cytoplasmic", "promotes tp53 cytoplasmic translocation and", "tp53 cytoplasmic translocation and proteasome", "cytoplasmic translocation and proteasome mediated", "translocation and proteasome mediated degradation", "proteasome mediated degradation monte", "mediated degradation monte et", "degradation monte et al.", "monte et al. 2004 .", "et al. 2004 . relocation", "al. 2004 . relocation of", "2004 . relocation of gtse1", ". relocation of gtse1 to", "relocation of gtse1 to the", "of gtse1 to the nucleus", "gtse1 to the nucleus in", "to the nucleus in g2", "the nucleus in g2 phase", "nucleus in g2 phase depends", "in g2 phase depends on", "g2 phase depends on plk1", "phase depends on plk1 mediated", "depends on plk1 mediated phosphorylation", "on plk1 mediated phosphorylation of", "plk1 mediated phosphorylation of gtse1", "phosphorylation of gtse1 liu", "of gtse1 liu et", "gtse1 liu et al.", "liu et al. 2010 .

gtse1", "et al. 2010 .

gtse1 facilitated", "al. 2010 .

gtse1 facilitated down", "2010 .

gtse1 facilitated down regulation", ".

gtse1 facilitated down regulation of", "facilitated down regulation of tp53", "down regulation of tp53 in", "regulation of tp53 in g2", "of tp53 in g2 allows", "tp53 in g2 allows cells", "in g2 allows cells to", "g2 allows cells to avoid", "allows cells to avoid tp53", "cells to avoid tp53 mediated", "to avoid tp53 mediated apoptosis", "avoid tp53 mediated apoptosis upon", "tp53 mediated apoptosis upon dna", "mediated apoptosis upon dna damage", "apoptosis upon dna damage and", "upon dna damage and to", "dna damage and to re", "damage and to re enter", "and to re enter cell", "to re enter cell cycle", "enter cell cycle monte", "cell cycle monte et", "cycle monte et al.", "monte et al. 2003 .", "et al. 2003 . while", "al. 2003 . while tp53", "2003 . while tp53 down", ". while tp53 down regulation", "while tp53 down regulation mediated", "tp53 down regulation mediated by", "down regulation mediated by gtse1", "regulation mediated by gtse1 in", "mediated by gtse1 in g2", "by gtse1 in g2 correlates", "gtse1 in g2 correlates with", "in g2 correlates with decreased", "g2 correlates with decreased expression", "correlates with decreased expression of", "with decreased expression of tp53", "decreased expression of tp53 target", "expression of tp53 target genes", "of tp53 target genes involved", "tp53 target genes involved in", "target genes involved in apoptosis", "genes involved in apoptosis and", "involved in apoptosis and cell", "in apoptosis and cell cycle", "apoptosis and cell cycle arrest", "cell cycle arrest gtse1", "cycle arrest gtse1 can", "arrest gtse1 can also", "gtse1 can also increase the", "can also increase the half", "also increase the half life", "increase the half life of", "the half life of the", "half life of the tp53", "life of the tp53 target", "of the tp53 target p21", "tp53 target p21 cdkn1a", "target p21 cdkn1a .", "p21 cdkn1a . gtse1", "cdkn1a . gtse1 mediated stabilization", ". gtse1 mediated stabilization of", "gtse1 mediated stabilization of cdkn1a", "mediated stabilization of cdkn1a involves", "stabilization of cdkn1a involves interaction", "of cdkn1a involves interaction of", "cdkn1a involves interaction of gtse1", "involves interaction of gtse1 with", "interaction of gtse1 with cdkn1a", "of gtse1 with cdkn1a and", "gtse1 with cdkn1a and its", "with cdkn1a and its chaperone", "cdkn1a and its chaperone complex", "its chaperone complex consisting", "chaperone complex consisting of", "complex consisting of hsp90", "consisting of hsp90 and fkbpl", "hsp90 and fkbpl wisp39", "wisp39 and may", "and may be involved in", "may be involved in resistance", "be involved in resistance to", "involved in resistance to paclitaxel", "in resistance to paclitaxel treatment", "to paclitaxel treatment bublik", "paclitaxel treatment bublik et", "treatment bublik et al.", "bublik et al. 2010 ." ] }, { "record_id": "GLY_000594_1_612", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8853383", "r hsa", "hsa 8853383", "r hsa 8853383" ] }, { "record_id": "GLY_000594_1_612", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lysosomal oligosaccharide", "oligosaccharide catabolism", "lysosomal oligosaccharide catabolism", "n glycosylation", "glycosylation is", "is one", "one of", "of the", "the most", "most common", "common co", "and posttranslational", "posttranslational modifications", "modifications of", "of eukaryotic", "eukaryotic proteins", "proteins occurring", "occurring in", "in the", "the er", "er lumen.", "lumen. n", "glycosylation plays", "plays pivotal", "pivotal roles", "roles in", "in protein", "protein folding", "folding and", "and intra", "or inter", "inter cellular", "cellular trafficking", "trafficking of", "of n", "n glycosylated", "glycosylated proteins.", "proteins. quality", "quality control", "control mechanisms", "mechanisms in", "er sift", "sift out", "out incorrectly", "incorrectly folded", "folded 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cleaved from the oligosaccharide", "from the oligosaccharide forming", "the oligosaccharide forming free", "oligosaccharide forming free oligosaccharides", "forming free oligosaccharides fos", "fos step wise", "step wise degradation of mannose", "wise degradation of mannose moieties", "of mannose moieties both", "mannose moieties both in", "moieties both in the", "in the cytosol suzuki", "the cytosol suzuki &", "cytosol suzuki & harada", "& harada 2014 and", "harada 2014 and then", "2014 and then in", "and then in the lysosome", "in the lysosome aronson", "the lysosome aronson &", "lysosome aronson & kuranda", "& kuranda 1989 winchester", "kuranda 1989 winchester 2005", "winchester 2005 results", "2005 results in", "results in complete degradation. breakdown", "in complete degradation. breakdown must", "complete degradation. breakdown must be", "degradation. breakdown must be complete", "breakdown must be complete to", "must be complete to avoid", "be complete to avoid lysosomal", "complete to avoid lysosomal storage", "to avoid lysosomal storage diseases", "avoid lysosomal storage diseases that", "lysosomal storage diseases that occur", "storage diseases that occur when", "diseases that occur when fragments", "that occur when fragments as", "occur when fragments as small", "when fragments as small as", "fragments as small as dimers", "as small as dimers are", "small as dimers are left", "as dimers are left undigested." ] }, { "record_id": "GLY_000594_1_613", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8853659", "r hsa", "hsa 8853659", "r hsa 8853659" ] }, { "record_id": "GLY_000594_1_613", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ret signaling", "the ret", "ret proto", "proto oncogene", "oncogene encodes", "encodes a", "a receptor", "receptor tyrosine", "tyrosine kinase", "kinase expressed", "expressed primarily", "primarily in", "in urogenital", "urogenital precursor", "precursor cells", "dopaminergic neurons", "motor neurons", "neurons and", "and neural", "neural crest", "crest progenitors", "progenitors and", "and derived", "derived cells.", "cells. .", ". it", "it is", "is essential", "essential for", "for kidney", "kidney genesis", "spermatogonial self", "self renewal", "renewal and", "and survivial", "axonal growth", "growth and", "and axon", "axon guidance", "guidance of", "of developing", "developing enteric", "enteric neurons", "parasympathetic neurons", "and somatosensory", "somatosensory neurons", "schuchardt et", "et al.", "al. 1994", "enomoto et", "al. 2001", "naughton et", "al. 2006", "kramer et", "luo et", "2009 .", ". ret", "ret was", "was identified", "identified as", "as the", "the causative", "causative gene", "gene for", "for human", "human papillary", "papillary thyroid", "thyroid carcinoma", "grieco et", "al. 1990", "multiple endocrine", "endocrine neoplasia", "type 2a", "mulligan et", "al. 1993", "type 2b", "hofstra et", "carlson et", "and hirschsprung's", "hirschsprung's disease", "romeo et", "edery et", "1994 .", "

ret contains", "contains a", "a cadherin", "cadherin related", "related motif", "motif and", "and a", "a cysteine", "cysteine rich", "rich domain", "domain in", "in the", "the extracellular", "extracellular domain", "takahashi et", "al. 1988", "1988 .", "is the", "the receptor", "receptor for", "for members", "members of", "of the", "the glial", "glial cell", "cell derived", "derived neurotrophic", "neurotrophic factor", "family of", "of ligands", "lin et", "kotzbauer et", "al. 1996", "baloh et", "al. 1998", "and persephin", "milbrandt et", "which form", "form a", "a family", "of neurotrophic", "neurotrophic factors.", "factors. to", "to stimulate", "stimulate ret", "these ligands", "ligands need", "need a", "a glycosylphosphatidylinositol", "anchored co", "co receptor", "collectively termed", "termed gdnf", "gdnf family", "family receptor", "receptor alpha", "treanor et", "jing et", "1996 .", ". the", "the four", "four members", "of this", "this family", "family have", "have different", "overlapping ligand", "ligand preferences.", "preferences. gfra1", "and gfra4", "gfra4 preferentially", "preferentially bind", "bind gdnf", "artn and", "and pspn", "creedon et", "al. 1997", "masure et", "al. 2000", "2000 .", "the gfra", "gfra co", "receptor can", "can come", "come from", "from the", "the same", "same cell", "cell as", "as ret", "or from", "from a", "a different", "different cell.", "cell. when", "when the", "the co", "receptor is", "is produced", "produced by", "by the", "is termed", "termed cis", "cis signaling.", "signaling. when", "by another", "another cell", "termed trans", "trans signaling.", "signaling. cis", "cis and", "and trans", "trans activation", "activation has", "has been", "been proposed", "proposed to", "to diversify", "diversify ret", "either by", "by recruiting", "recruiting different", "different downstream", "downstream effectors", "effectors or", "or by", "by changing", "changing the", "the kinetics", "kinetics or", "or efficacy", "efficacy of", "of kinase", "kinase activation", "tansey et", "paratcha et", "2001 .", ". whether", "whether cis", "trans signaling", "signaling has", "has significant", "significant differences", "differences in", "in vivo", "vivo is", "is unresolved", "fleming et", "al. 2015", "2015 .", ". different", "different gdnf", "family members", "members could", "could activate", "activate similar", "similar downstream", "downstream signaling", "signaling pathways", "pathways since", "since all", "all gfras", "gfras bind", "bind to", "to and", "and activate", "activate the", "same tyrosine", "kinase and", "and induce", "induce coordinated", "coordinated phosphorylation", "phosphorylation of", "same four", "four ret", "ret tyrosines", "and tyr1096", "with similar", "similar kinetics", "coulpier et", "al. 2002", "2002 .", ". however", "however the", "the exact", "exact ret", "pathways in", "in different", "different types", "types of", "of cells", "cells and", "and neurons", "neurons remain", "remain to", "to be", "be determined.", "the ret proto", "ret proto oncogene", "proto oncogene encodes", "oncogene encodes a", "encodes a receptor", "a receptor tyrosine", "receptor tyrosine kinase", "tyrosine kinase expressed", "kinase expressed primarily", "expressed primarily in", "primarily in urogenital", "in urogenital precursor", "urogenital precursor cells", "cells spermatogonocytes", "spermatogonocytes dopaminergic", "neurons motor", "motor neurons and", "neurons and neural", "and neural crest", "neural crest progenitors", "crest progenitors and", "progenitors and derived", "and derived cells.", "derived cells. .", "cells. . it", ". it is", "it is essential", "is essential for", "essential for kidney", "for kidney genesis", "genesis spermatogonial", "spermatogonial self renewal", "self renewal and", "renewal and survivial", "survivial specification", "specification migration", "migration axonal", "axonal growth and", "growth and axon", "and axon guidance", "axon guidance of", "guidance of developing", "of developing enteric", "developing enteric neurons", "neurons parasympathetic", "parasympathetic neurons and", "neurons and somatosensory", "and somatosensory neurons", "neurons schuchardt", "schuchardt et al.", "et al. 1994", "1994 enomoto", "enomoto et al.", "et al. 2001", "2001 naughton", "naughton et al.", "et al. 2006", "2006 kramer", "kramer et al.", "2006 luo", "luo et al.", "2006 2009", "2009 . ret", ". ret was", "ret was identified", "was identified as", "identified as the", "as the causative", "the causative gene", "causative gene for", "gene for human", "for human papillary", "human papillary thyroid", "papillary thyroid carcinoma", "carcinoma grieco", "grieco et al.", "et al. 1990", "multiple endocrine neoplasia", "neoplasia men", "men type", "2a mulligan", "mulligan et al.", "et al. 1993", "2b hofstra", "hofstra et al.", "1994 carlson", "carlson et al.", "and hirschsprung's disease", "disease romeo", "romeo et al.", "1994 edery", "edery et al.", "al. 1994 .", ".

ret", "

ret contains a", "contains a cadherin", "a cadherin related", "cadherin related motif", "related motif and", "motif and a", "and a cysteine", "a cysteine rich", "cysteine rich domain", "rich domain in", "domain in the", "in the extracellular", "the extracellular domain", "domain takahashi", "takahashi et al.", "et al. 1988", "al. 1988 .", "1988 . it", "it is the", "is the receptor", "the receptor for", "receptor for members", "for members of", "members of the", "of the glial", "the glial cell", "glial cell derived", "cell derived neurotrophic", "derived neurotrophic factor", "factor gdnf", "family of ligands", "ligands gdnf", "gdnf lin", "lin et al.", "neurturin nrtn", "kotzbauer et al.", "et al. 1996", "artemin artn", "baloh et al.", "et al. 1998", "persephin pspn", "milbrandt et al.", "which form a", "form a family", "a family of", "family of neurotrophic", "of neurotrophic factors.", "neurotrophic factors. to", "factors. to stimulate", "to stimulate ret", "ret these", "these ligands need", "ligands need a", "need a glycosylphosphatidylinositol", "glycosylphosphatidylinositol gpi", "gpi anchored", "anchored co receptor", "receptor collectively", "collectively termed gdnf", "termed gdnf family", "gdnf family receptor", "family receptor alpha", "alpha gfra", "treanor et al.", "1996 jing", "jing et al.", "al. 1996 .", "1996 . the", ". the four", "the four members", "four members of", "members of this", "of this family", "this family have", "family have different", "different overlapping", "overlapping ligand preferences.", "ligand preferences. gfra1", "gfra1 gfra2", "gfra2 gfra3", "gfra3 and", "and gfra4 preferentially", "gfra4 preferentially bind", "preferentially bind gdnf", "gdnf nrtn", "nrtn artn", "artn and pspn", "pspn respectively", "respectively jing", "1996 1997", "1997 creedon", "creedon et al.", "et al. 1997", "1997 baloh", "1997 1998", "1998 masure", "masure et al.", "et al. 2000", "al. 2000 .", "2000 . the", ". the gfra", "the gfra co", "gfra co receptor", "co receptor can", "receptor can come", "can come from", "come from the", "from the same", "the same cell", "same cell as", "cell as ret", "ret or", "or from a", "from a different", "a different cell.", "different cell. when", "cell. when the", "when the co", "the co receptor", "co receptor is", "receptor is produced", "is produced by", "produced by the", "by the same", "ret it", "it is termed", "is termed cis", "termed cis signaling.", "cis signaling. when", "signaling. when the", "produced by another", "by another cell", "cell it", "is termed trans", "termed trans signaling.", "trans signaling. cis", "signaling. cis and", "cis and trans", "and trans activation", "trans activation has", "activation has been", "has been proposed", "been proposed to", "proposed to diversify", "to diversify ret", "diversify ret signaling", "signaling either", "either by recruiting", "by recruiting different", "recruiting different downstream", "different downstream effectors", "downstream effectors or", "effectors or by", "or by changing", "by changing the", "changing the kinetics", "the kinetics or", "kinetics or efficacy", "or efficacy of", "efficacy of kinase", "of kinase activation", "activation tansey", "tansey et al.", "2000 paratcha", "paratcha et al.", "al. 2001 .", "2001 . whether", ". whether cis", "whether cis and", "and trans signaling", "trans signaling has", "signaling has significant", "has significant differences", "significant differences in", "differences in vivo", "in vivo is", "vivo is unresolved", "unresolved fleming", "fleming et al.", "et al. 2015", "al. 2015 .", "2015 . different", ". different gdnf", "different gdnf family", "gdnf family members", "family members could", "members could activate", "could activate similar", "activate similar downstream", "similar downstream signaling", "downstream signaling pathways", "signaling pathways since", "pathways since all", "since all gfras", "all gfras bind", "gfras bind to", "bind to and", "to and activate", "and activate the", "activate the same", "the same tyrosine", "same tyrosine kinase", "tyrosine kinase and", "kinase and induce", "and induce coordinated", "induce coordinated phosphorylation", "coordinated phosphorylation of", "phosphorylation of the", "of the same", "the same four", "same four ret", "four ret tyrosines", "tyrosines tyr905", "tyr905 tyr1015", "tyr1015 tyr1062", "tyr1062 and", "tyr1096 with", "with similar kinetics", "kinetics coulpier", "coulpier et al.", "et al. 2002", "al. 2002 .", "2002 . however", ". however the", "however the exact", "the exact ret", "exact ret signaling", "ret signaling pathways", "signaling pathways in", "pathways in different", "in different types", "different types of", "types of cells", "of cells and", "cells and neurons", "and neurons remain", "neurons remain to", "remain to be", "to be determined.", "the ret proto oncogene", "ret proto oncogene encodes", "proto oncogene encodes a", "oncogene encodes a receptor", "encodes a receptor tyrosine", "a receptor tyrosine kinase", "receptor tyrosine kinase expressed", "tyrosine kinase expressed primarily", "kinase expressed primarily in", "expressed primarily in urogenital", "primarily in urogenital precursor", "in urogenital precursor cells", "precursor cells spermatogonocytes", "spermatogonocytes dopaminergic neurons", "dopaminergic neurons motor", "neurons motor neurons", "motor neurons and neural", "neurons and neural crest", "and neural crest progenitors", "neural crest progenitors and", "crest progenitors and derived", "progenitors and derived cells.", "and derived cells. .", "derived cells. . it", "cells. . it is", ". it is essential", "it is essential for", "is essential for kidney", "essential for kidney genesis", "kidney genesis spermatogonial", "genesis spermatogonial self", "spermatogonial self renewal and", "self renewal and survivial", "and survivial specification", "migration axonal growth", "axonal growth and axon", "growth and axon guidance", "and axon guidance of", "axon guidance of developing", "guidance of developing enteric", "of developing enteric neurons", "enteric neurons motor", "motor neurons parasympathetic", "neurons parasympathetic neurons", "parasympathetic neurons and somatosensory", "neurons and somatosensory neurons", "somatosensory neurons schuchardt", "neurons schuchardt et", "schuchardt et al. 1994", "al. 1994 enomoto", "1994 enomoto et", "enomoto et al. 2001", "al. 2001 naughton", "2001 naughton et", "naughton et al. 2006", "al. 2006 kramer", "2006 kramer et", "kramer et al. 2006", "al. 2006 luo", "2006 luo et", "luo et al. 2006", "al. 2006 2009", "2006 2009 .", "2009 . ret was", ". ret was identified", "ret was identified as", "was identified as the", "identified as the causative", "as the causative gene", "the causative gene for", "causative gene for human", "gene for human papillary", "for human papillary thyroid", "human papillary thyroid carcinoma", "thyroid carcinoma grieco", "carcinoma grieco et", "grieco et al. 1990", "1990 multiple", "endocrine neoplasia men", "men type 2a", "type 2a mulligan", "2a mulligan et", "mulligan et al. 1993", "1993 type", "type 2b hofstra", "2b hofstra et", "hofstra et al. 1994", "al. 1994 carlson", "1994 carlson et", "carlson et al. 1994", "1994 and", "hirschsprung's disease romeo", "disease romeo et", "romeo et al. 1994", "al. 1994 edery", "1994 edery et", "edery et al. 1994", "et al. 1994 .", "1994 .

ret", ".

ret contains", "

ret contains a cadherin", "contains a cadherin related", "a cadherin related motif", "cadherin related motif and", "related motif and a", "motif and a cysteine", "and a cysteine rich", "a cysteine rich domain", "cysteine rich domain in", "rich domain in the", "domain in the extracellular", "in the extracellular domain", "extracellular domain takahashi", "domain takahashi et", "takahashi et al. 1988", "et al. 1988 .", "al. 1988 . it", "1988 . it is", ". it is the", "it is the receptor", "is the receptor for", "the receptor for members", "receptor for members of", "for members of the", "members of the glial", "of the glial cell", "the glial cell derived", "glial cell derived neurotrophic", "cell derived neurotrophic factor", "neurotrophic factor gdnf", "gdnf family of", "of ligands gdnf", "gdnf lin et", "lin et al. 1993", "1993 neurturin", "nrtn kotzbauer", "kotzbauer et al. 1996", "1996 artemin", "artn baloh", "baloh et al. 1998", "1998 and", "and persephin pspn", "pspn milbrandt", "milbrandt et al. 1998", "1998 which", "which form a family", "form a family of", "a family of neurotrophic", "family of neurotrophic factors.", "of neurotrophic factors. to", "neurotrophic factors. to stimulate", "factors. to stimulate ret", "stimulate ret these", "ret these ligands", "these ligands need a", "ligands need a glycosylphosphatidylinositol", "a glycosylphosphatidylinositol gpi", "gpi anchored co", "co receptor collectively", "receptor collectively termed", "collectively termed gdnf family", "termed gdnf family receptor", "gdnf family receptor alpha", "receptor alpha gfra", "gfra treanor", "treanor et al. 1996", "al. 1996 jing", "1996 jing et", "jing et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the four", ". the four members", "the four members of", "four members of this", "members of this family", "of this family have", "this family have different", "have different overlapping", "different overlapping ligand", "overlapping ligand preferences. gfra1", "preferences. gfra1 gfra2", "gfra3 and gfra4", "and gfra4 preferentially bind", "gfra4 preferentially bind gdnf", "bind gdnf nrtn", "nrtn artn and", "and pspn respectively", "respectively jing et", "al. 1996 1997", "1997 creedon et", "creedon et al. 1997", "al. 1997 baloh", "1997 baloh et", "baloh et al. 1997", "al. 1997 1998", "1998 masure et", "masure et al. 2000", "et al. 2000 .", "al. 2000 . the", "2000 . the gfra", ". the gfra co", "the gfra co receptor", "gfra co receptor can", "co receptor can come", "receptor can come from", "can come from the", "come from the same", "from the same cell", "the same cell as", "same cell as ret", "as ret or", "ret or from", "or from a different", "from a different cell.", "a different cell. when", "different cell. when the", "cell. when the co", "when the co receptor", "the co receptor is", "co receptor is produced", "receptor is produced by", "is produced by the", "produced by the same", "by the same cell", "as ret it", "ret it is", "it is termed cis", "is termed cis signaling.", "termed cis signaling. when", "cis signaling. when the", "signaling. when the co", "is produced by another", "produced by another cell", "another cell it", "cell it is", "it is termed trans", "is termed trans signaling.", "termed trans signaling. cis", "trans signaling. cis and", "signaling. cis and trans", "cis and trans activation", "and trans activation has", "trans activation has been", "activation has been proposed", "has been proposed to", "been proposed to diversify", "proposed to diversify ret", "to diversify ret signaling", "ret signaling either", "signaling either by", "either by recruiting different", "by recruiting different downstream", "recruiting different downstream effectors", "different downstream effectors or", "downstream effectors or by", "effectors or by changing", "or by changing the", "by changing the kinetics", "changing the kinetics or", "the kinetics or efficacy", "kinetics or efficacy of", "or efficacy of kinase", "efficacy of kinase activation", "kinase activation tansey", "activation tansey et", "tansey et al. 2000", "al. 2000 paratcha", "2000 paratcha et", "paratcha et al. 2001", "et al. 2001 .", "al. 2001 . whether", "2001 . whether cis", ". whether cis and", "whether cis and trans", "cis and trans signaling", "and trans signaling has", "trans signaling has significant", "signaling has significant differences", "has significant differences in", "significant differences in vivo", "differences in vivo is", "in vivo is unresolved", "is unresolved fleming", "unresolved fleming et", "fleming et al. 2015", "et al. 2015 .", "al. 2015 . different", "2015 . different gdnf", ". different gdnf family", "different gdnf family members", "gdnf family members could", "family members could activate", "members could activate similar", "could activate similar downstream", "activate similar downstream signaling", "similar downstream signaling pathways", "downstream signaling pathways since", "signaling pathways since all", "pathways since all gfras", "since all gfras bind", "all gfras bind to", "gfras bind to and", "bind to and activate", "to and activate the", "and activate the same", "activate the same tyrosine", "the same tyrosine kinase", "same tyrosine kinase and", "tyrosine kinase and induce", "kinase and induce coordinated", "and induce coordinated phosphorylation", "induce coordinated phosphorylation of", "coordinated phosphorylation of the", "phosphorylation of the same", "of the same four", "the same four ret", "same four ret tyrosines", "ret tyrosines tyr905", "tyr1062 and tyr1096", "and tyr1096 with", "tyr1096 with similar", "similar kinetics coulpier", "kinetics coulpier et", "coulpier et al. 2002", "et al. 2002 .", "al. 2002 . however", "2002 . however the", ". however the exact", "however the exact ret", "the exact ret signaling", "exact ret signaling pathways", "ret signaling pathways in", "signaling pathways in different", "pathways in different types", "in different types of", "different types of cells", "types of cells and", "of cells and neurons", "cells and neurons remain", "and neurons remain to", "neurons remain to be", "remain to be determined.", "the ret proto oncogene encodes", "ret proto oncogene encodes a", "proto oncogene encodes a receptor", "oncogene encodes a receptor tyrosine", "encodes a receptor tyrosine kinase", "a receptor tyrosine kinase expressed", "receptor tyrosine kinase expressed primarily", "tyrosine kinase expressed primarily in", "kinase expressed primarily in urogenital", "expressed primarily in urogenital precursor", "primarily in urogenital precursor cells", "urogenital precursor cells spermatogonocytes", "cells spermatogonocytes dopaminergic", "dopaminergic neurons motor neurons", "neurons motor neurons and", "motor neurons and neural crest", "neurons and neural crest progenitors", "and neural crest progenitors and", "neural crest progenitors and derived", "crest progenitors and derived cells.", "progenitors and derived cells. .", "and derived cells. . it", "derived cells. . it is", "cells. . it is essential", ". it is essential for", "it is essential for kidney", "is essential for kidney genesis", "for kidney genesis spermatogonial", "kidney genesis spermatogonial self", "genesis spermatogonial self renewal", "spermatogonial self renewal and survivial", "renewal and survivial specification", "survivial specification migration", "specification migration axonal", "migration axonal growth and", "axonal growth and axon guidance", "growth and axon guidance of", "and axon guidance of developing", "axon guidance of developing enteric", "guidance of developing enteric neurons", "developing enteric neurons motor", "enteric neurons motor neurons", "motor neurons parasympathetic neurons", "neurons parasympathetic neurons and", "parasympathetic neurons and somatosensory neurons", "and somatosensory neurons schuchardt", "somatosensory neurons schuchardt et", "neurons schuchardt et al.", "et al. 1994 enomoto", "al. 1994 enomoto et", "1994 enomoto et al.", "et al. 2001 naughton", "al. 2001 naughton et", "2001 naughton et al.", "et al. 2006 kramer", "al. 2006 kramer et", "2006 kramer et al.", "et al. 2006 luo", "al. 2006 luo et", "2006 luo et al.", "et al. 2006 2009", "al. 2006 2009 .", "2006 2009 . ret", "2009 . ret was identified", ". ret was identified as", "ret was identified as the", "was identified as the causative", "identified as the causative gene", "as the causative gene for", "the causative gene for human", "causative gene for human papillary", "gene for human papillary thyroid", "for human papillary thyroid carcinoma", "papillary thyroid carcinoma grieco", "thyroid carcinoma grieco et", "carcinoma grieco et al.", "al. 1990 multiple", "1990 multiple endocrine", "multiple endocrine neoplasia men", "neoplasia men type", "type 2a mulligan et", "2a mulligan et al.", "al. 1993 type", "1993 type 2b", "type 2b hofstra et", "2b hofstra et al.", "et al. 1994 carlson", "al. 1994 carlson et", "1994 carlson et al.", "al. 1994 and", "1994 and hirschsprung's", "and hirschsprung's disease romeo", "hirschsprung's disease romeo et", "disease romeo et al.", "et al. 1994 edery", "al. 1994 edery et", "1994 edery et al.", "edery et al. 1994 .", "al. 1994 .

ret", "1994 .

ret contains", ".

ret contains a", "

ret contains a cadherin related", "contains a cadherin related motif", "a cadherin related motif and", "cadherin related motif and a", "related motif and a cysteine", "motif and a cysteine rich", "and a cysteine rich domain", "a cysteine rich domain in", "cysteine rich domain in the", "rich domain in the extracellular", "domain in the extracellular domain", "the extracellular domain takahashi", "extracellular domain takahashi et", "domain takahashi et al.", "takahashi et al. 1988 .", "et al. 1988 . it", "al. 1988 . it is", "1988 . it is the", ". it is the receptor", "it is the receptor for", "is the receptor for members", "the receptor for members of", "receptor for members of the", "for members of the glial", "members of the glial cell", "of the glial cell derived", "the glial cell derived neurotrophic", "glial cell derived neurotrophic factor", "derived neurotrophic factor gdnf", "factor gdnf family", "gdnf family of ligands", "family of ligands gdnf", "ligands gdnf lin", "gdnf lin et al.", "al. 1993 neurturin", "nrtn kotzbauer et", "al. 1996 artemin", "artn baloh et", "al. 1998 and", "1998 and persephin", "pspn milbrandt et", "al. 1998 which", "1998 which form", "which form a family of", "form a family of neurotrophic", "a family of neurotrophic factors.", "family of neurotrophic factors. to", "of neurotrophic factors. to stimulate", "neurotrophic factors. to stimulate ret", "to stimulate ret these", "stimulate ret these ligands", "ret these ligands need", "these ligands need a glycosylphosphatidylinositol", "need a glycosylphosphatidylinositol gpi", "glycosylphosphatidylinositol gpi anchored", "gpi anchored co receptor", "anchored co receptor collectively", "co receptor collectively termed", "receptor collectively termed gdnf", "collectively termed gdnf family receptor", "termed gdnf family receptor alpha", "family receptor alpha gfra", "gfra treanor et", "et al. 1996 jing", "al. 1996 jing et", "1996 jing et al.", "jing et al. 1996 .", "et al. 1996 . the", "al. 1996 . the four", "1996 . the four members", ". the four members of", "the four members of this", "four members of this family", "members of this family have", "of this family have different", "family have different overlapping", "have different overlapping ligand", "different overlapping ligand preferences.", "ligand preferences. gfra1 gfra2", "gfra1 gfra2 gfra3", "gfra2 gfra3 and", "gfra3 and gfra4 preferentially", "and gfra4 preferentially bind gdnf", "preferentially bind gdnf nrtn", "gdnf nrtn artn", "nrtn artn and pspn", "artn and pspn respectively", "pspn respectively jing", "respectively jing et al.", "et al. 1996 1997", "1996 1997 creedon", "1997 creedon et al.", "et al. 1997 baloh", "al. 1997 baloh et", "1997 baloh et al.", "et al. 1997 1998", "1997 1998 masure", "1998 masure et al.", "masure et al. 2000 .", "et al. 2000 . the", "al. 2000 . the gfra", "2000 . the gfra co", ". the gfra co receptor", "the gfra co receptor can", "gfra co receptor can come", "co receptor can come from", "receptor can come from the", "can come from the same", "come from the same cell", "from the same cell as", "the same cell as ret", "cell as ret or", "as ret or from", "ret or from a", "or from a different cell.", "from a different cell. when", "a different cell. when the", "different cell. when the co", "cell. when the co receptor", "when the co receptor is", "the co receptor is produced", "co receptor is produced by", "receptor is produced by the", "is produced by the same", "produced by the same cell", "by the same cell as", "cell as ret it", "as ret it is", "ret it is termed", "it is termed cis signaling.", "is termed cis signaling. when", "termed cis signaling. when the", "cis signaling. when the co", "signaling. when the co receptor", "receptor is produced by another", "is produced by another cell", "by another cell it", "another cell it is", "cell it is termed", "it is termed trans signaling.", "is termed trans signaling. cis", "termed trans signaling. cis and", "trans signaling. cis and trans", "signaling. cis and trans activation", "cis and trans activation has", "and trans activation has been", "trans activation has been proposed", "activation has been proposed to", "has been proposed to diversify", "been proposed to diversify ret", "proposed to diversify ret signaling", "diversify ret signaling either", "ret signaling either by", "signaling either by recruiting", "either by recruiting different downstream", "by recruiting different downstream effectors", "recruiting different downstream effectors or", "different downstream effectors or by", "downstream effectors or by changing", "effectors or by changing the", "or by changing the kinetics", "by changing the kinetics or", "changing the kinetics or efficacy", "the kinetics or efficacy of", "kinetics or efficacy of kinase", "or efficacy of kinase activation", "of kinase activation tansey", "kinase activation tansey et", "activation tansey et al.", "et al. 2000 paratcha", "al. 2000 paratcha et", "2000 paratcha et al.", "paratcha et al. 2001 .", "et al. 2001 . whether", "al. 2001 . whether cis", "2001 . whether cis and", ". whether cis and trans", "whether cis and trans signaling", "cis and trans signaling has", "and trans signaling has significant", "trans signaling has significant differences", "signaling has significant differences in", "has significant differences in vivo", "significant differences in vivo is", "differences in vivo is unresolved", "vivo is unresolved fleming", "is unresolved fleming et", "unresolved fleming et al.", "fleming et al. 2015 .", "et al. 2015 . different", "al. 2015 . different gdnf", "2015 . different gdnf family", ". different gdnf family members", "different gdnf family members could", "gdnf family members could activate", "family members could activate similar", "members could activate similar downstream", "could activate similar downstream signaling", "activate similar downstream signaling pathways", "similar downstream signaling pathways since", "downstream signaling pathways since all", "signaling pathways since all gfras", "pathways since all gfras bind", "since all gfras bind to", "all gfras bind to and", "gfras bind to and activate", "bind to and activate the", "to and activate the same", "and activate the same tyrosine", "activate the same tyrosine kinase", "the same tyrosine kinase and", "same tyrosine kinase and induce", "tyrosine kinase and induce coordinated", "kinase and induce coordinated phosphorylation", "and induce coordinated phosphorylation of", "induce coordinated phosphorylation of the", "coordinated phosphorylation of the same", "phosphorylation of the same four", "of the same four ret", "the same four ret tyrosines", "four ret tyrosines tyr905", "tyrosines tyr905 tyr1015", "tyr905 tyr1015 tyr1062", "tyr1015 tyr1062 and", "and tyr1096 with similar", "tyr1096 with similar kinetics", "with similar kinetics coulpier", "similar kinetics coulpier et", "kinetics coulpier et al.", "coulpier et al. 2002 .", "et al. 2002 . however", "al. 2002 . however the", "2002 . however the exact", ". however the exact ret", "however the exact ret signaling", "the exact ret signaling pathways", "exact ret signaling pathways in", "ret signaling pathways in different", "signaling pathways in different types", "pathways in different types of", "in different types of cells", "different types of cells and", "types of cells and neurons", "of cells and neurons remain", "cells and neurons remain to", "and neurons remain to be", "neurons remain to be determined." ] }, { "record_id": "GLY_000594_1_614", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8854050", "r hsa", "hsa 8854050", "r hsa 8854050" ] }, { "record_id": "GLY_000594_1_614", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fbxl7 down", "down regulates", "regulates aurka", "aurka during", "during mitotic", "mitotic entry", "entry and", "and in", "in early", "early mitosis", "fbxl7 down regulates", "down regulates aurka", "regulates aurka during", "aurka during mitotic", "during mitotic entry", "mitotic entry and", "entry and in", "and in early", "in early mitosis", "fbxl7 down regulates aurka", "down regulates aurka during", "regulates aurka during mitotic", "aurka during mitotic entry", "during mitotic entry and", "mitotic entry and in", "entry and in early", "and in early mitosis", "fbxl7 down regulates aurka during", "down regulates aurka during mitotic", "regulates aurka during mitotic entry", "aurka during mitotic entry and", "during mitotic entry and in", "mitotic entry and in early", "entry and in early mitosis", "the protein", "protein levels", "levels of", "of aurora", "aurora kinase", "kinase a", "mitosis can", "can be", "be reduced", "reduced by", "by the", "the action", "action of", "of the", "the scf", "scf fbxl7", "fbxl7 e3", "e3 ubiquitin", "ubiquitin ligase", "ligase complex", "complex consisting", "consisting of", "of skp1", "rbx1 and", "and fbxl7", "fbxl7 subunits.", "subunits. fbxl7", "fbxl7 is", "is the", "the substrate", "substrate recognition", "recognition subunit", "subunit of", "fbxl7 complex", "complex that", "that associates", "associates with", "with the", "the centrosome", "centrosome bound", "bound aurka", "promoting its", "its ubiquitination", "ubiquitination and", "and proteasome", "proteasome mediated", "mediated degradation.", "degradation. overexpression", "overexpression of", "of fbxl7", "fbxl7 results", "results in", "in g2/m", "g2/m cell", "cell cycle", "cycle arrest", "arrest and", "and apoptosis", "coon et", "et al.", "al. 2011", "2011 .

fbxl7", ".

fbxl7 protein", "levels are", "are down", "down regulated", "regulated by", "scf fbxl18", "fbxl18 e3", "and the", "subunit fbxl18.", "fbxl18. fbxl18", "fbxl18 binds", "binds to", "to the", "the fq", "fq motif", "motif of", "targeting it", "it for", "for ubiquitination", "mediated degradation", "counteracting its", "its pro", "pro apoptotic", "apoptotic activity", "liu et", "al. 2015", "2015 .", ". cell", "cycle stage", "stage dependency", "dependency of", "of down", "down regulation", "regulation of", "fbxl7 by", "by fbxl18", "fbxl18 is", "is unknown.", "the protein levels", "protein levels of", "levels of aurora", "of aurora kinase", "aurora kinase a", "a aurka", "early mitosis can", "mitosis can be", "can be reduced", "be reduced by", "reduced by the", "by the action", "the action of", "action of the", "of the scf", "the scf fbxl7", "scf fbxl7 e3", "fbxl7 e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase complex", "ligase complex consisting", "complex consisting of", "consisting of skp1", "skp1 cul1", "cul1 rbx1", "rbx1 and fbxl7", "and fbxl7 subunits.", "fbxl7 subunits. fbxl7", "subunits. fbxl7 is", "fbxl7 is the", "is the substrate", "the substrate recognition", "substrate recognition subunit", "recognition subunit of", "subunit of the", "scf fbxl7 complex", "fbxl7 complex that", "complex that associates", "that associates with", "associates with the", "with the centrosome", "the centrosome bound", "centrosome bound aurka", "aurka promoting", "promoting its ubiquitination", "its ubiquitination and", "ubiquitination and proteasome", "and proteasome mediated", "proteasome mediated degradation.", "mediated degradation. overexpression", "degradation. overexpression of", "overexpression of fbxl7", "of fbxl7 results", "fbxl7 results in", "results in g2/m", "in g2/m cell", "g2/m cell cycle", "cell cycle arrest", "cycle arrest and", "arrest and apoptosis", "apoptosis coon", "coon et al.", "et al. 2011", "al. 2011 .

fbxl7", "2011 .

fbxl7 protein", ".

fbxl7 protein levels", "protein levels are", "levels are down", "are down regulated", "down regulated by", "regulated by the", "the scf fbxl18", "scf fbxl18 e3", "fbxl18 e3 ubiquitin", "rbx1 and the", "and the substrate", "recognition subunit fbxl18.", "subunit fbxl18. fbxl18", "fbxl18. fbxl18 binds", "fbxl18 binds to", "binds to the", "to the fq", "the fq motif", "fq motif of", "motif of fbxl7", "fbxl7 targeting", "targeting it for", "it for ubiquitination", "for ubiquitination and", "proteasome mediated degradation", "degradation counteracting", "counteracting its pro", "its pro apoptotic", "pro apoptotic activity", "activity liu", "liu et al.", "et al. 2015", "al. 2015 .", "2015 . cell", ". cell cycle", "cell cycle stage", "cycle stage dependency", "stage dependency of", "dependency of down", "of down regulation", "down regulation of", "regulation of fbxl7", "of fbxl7 by", "fbxl7 by fbxl18", "by fbxl18 is", "fbxl18 is unknown.", "the protein levels of", "protein levels of aurora", "levels of aurora kinase", "of aurora kinase a", "kinase a aurka", "in early mitosis can", "early mitosis can be", "mitosis can be reduced", "can be reduced by", "be reduced by the", "reduced by the action", "by the action of", "the action of the", "action of the scf", "of the scf fbxl7", "the scf fbxl7 e3", "scf fbxl7 e3 ubiquitin", "fbxl7 e3 ubiquitin ligase", "e3 ubiquitin ligase complex", "ubiquitin ligase complex consisting", "ligase complex consisting of", "complex consisting of skp1", "of skp1 cul1", "cul1 rbx1 and", "rbx1 and fbxl7 subunits.", "and fbxl7 subunits. fbxl7", "fbxl7 subunits. fbxl7 is", "subunits. fbxl7 is the", "fbxl7 is the substrate", "is the substrate recognition", "the substrate recognition subunit", "substrate recognition subunit of", "recognition subunit of the", "subunit of the scf", "the scf fbxl7 complex", "scf fbxl7 complex that", "fbxl7 complex that associates", "complex that associates with", "that associates with the", "associates with the centrosome", "with the centrosome bound", "the centrosome bound aurka", "bound aurka promoting", "aurka promoting its", "promoting its ubiquitination and", "its ubiquitination and proteasome", "ubiquitination and proteasome mediated", "and proteasome mediated degradation.", "proteasome mediated degradation. overexpression", "mediated degradation. overexpression of", "degradation. overexpression of fbxl7", "overexpression of fbxl7 results", "of fbxl7 results in", "fbxl7 results in g2/m", "results in g2/m cell", "in g2/m cell cycle", "g2/m cell cycle arrest", "cell cycle arrest and", "cycle arrest and apoptosis", "and apoptosis coon", "apoptosis coon et", "coon et al. 2011", "et al. 2011 .

fbxl7", "al. 2011 .

fbxl7 protein", "2011 .

fbxl7 protein levels", ".

fbxl7 protein levels are", "protein levels are down", "levels are down regulated", "are down regulated by", "down regulated by the", "regulated by the action", "of the scf fbxl18", "the scf fbxl18 e3", "scf fbxl18 e3 ubiquitin", "fbxl18 e3 ubiquitin ligase", "rbx1 and the substrate", "and the substrate recognition", "substrate recognition subunit fbxl18.", "recognition subunit fbxl18. fbxl18", "subunit fbxl18. fbxl18 binds", "fbxl18. fbxl18 binds to", "fbxl18 binds to the", "binds to the fq", "to the fq motif", "the fq motif of", "fq motif of fbxl7", "of fbxl7 targeting", "fbxl7 targeting it", "targeting it for ubiquitination", "it for ubiquitination and", "for ubiquitination and proteasome", "and proteasome mediated degradation", "mediated degradation counteracting", "degradation counteracting its", "counteracting its pro apoptotic", "its pro apoptotic activity", "apoptotic activity liu", "activity liu et", "liu et al. 2015", "et al. 2015 .", "al. 2015 . cell", "2015 . cell cycle", ". cell cycle stage", "cell cycle stage dependency", "cycle stage dependency of", "stage dependency of down", "dependency of down regulation", "of down regulation of", "down regulation of fbxl7", "regulation of fbxl7 by", "of fbxl7 by fbxl18", "fbxl7 by fbxl18 is", "by fbxl18 is unknown.", "the protein levels of aurora", "protein levels of aurora kinase", "levels of aurora kinase a", "aurora kinase a aurka", "a aurka during", "and in early mitosis can", "in early mitosis can be", "early mitosis can be reduced", "mitosis can be reduced by", "can be reduced by the", "be reduced by the action", "reduced by the action of", "by the action of the", "the action of the scf", "action of the scf fbxl7", "of the scf fbxl7 e3", "the scf fbxl7 e3 ubiquitin", "scf fbxl7 e3 ubiquitin ligase", "fbxl7 e3 ubiquitin ligase complex", "e3 ubiquitin ligase complex consisting", "ubiquitin ligase complex consisting of", "ligase complex consisting of skp1", "consisting of skp1 cul1", "skp1 cul1 rbx1", "cul1 rbx1 and fbxl7", "rbx1 and fbxl7 subunits. fbxl7", "and fbxl7 subunits. fbxl7 is", "fbxl7 subunits. fbxl7 is the", "subunits. fbxl7 is the substrate", "fbxl7 is the substrate recognition", "is the substrate recognition subunit", "the substrate recognition subunit of", "substrate recognition subunit of the", "recognition subunit of the scf", "subunit of the scf fbxl7", "of the scf fbxl7 complex", "the scf fbxl7 complex that", "scf fbxl7 complex that associates", "fbxl7 complex that associates with", "complex that associates with the", "that associates with the centrosome", "associates with the centrosome bound", "with the centrosome bound aurka", "centrosome bound aurka promoting", "bound aurka promoting its", "aurka promoting its ubiquitination", "promoting its ubiquitination and proteasome", "its ubiquitination and proteasome mediated", "ubiquitination and proteasome mediated degradation.", "and proteasome mediated degradation. overexpression", "proteasome mediated degradation. overexpression of", "mediated degradation. overexpression of fbxl7", "degradation. overexpression of fbxl7 results", "overexpression of fbxl7 results in", "of fbxl7 results in g2/m", "fbxl7 results in g2/m cell", "results in g2/m cell cycle", "in g2/m cell cycle arrest", "g2/m cell cycle arrest and", "cell cycle arrest and apoptosis", "arrest and apoptosis coon", "and apoptosis coon et", "apoptosis coon et al.", "coon et al. 2011 .

fbxl7", "et al. 2011 .

fbxl7 protein", "al. 2011 .

fbxl7 protein levels", "2011 .

fbxl7 protein levels are", ".

fbxl7 protein levels are down", "protein levels are down regulated", "levels are down regulated by", "are down regulated by the", "down regulated by the action", "regulated by the action of", "action of the scf fbxl18", "of the scf fbxl18 e3", "the scf fbxl18 e3 ubiquitin", "scf fbxl18 e3 ubiquitin ligase", "fbxl18 e3 ubiquitin ligase complex", "cul1 rbx1 and the", "rbx1 and the substrate recognition", "and the substrate recognition subunit", "the substrate recognition subunit fbxl18.", "substrate recognition subunit fbxl18. fbxl18", "recognition subunit fbxl18. fbxl18 binds", "subunit fbxl18. fbxl18 binds to", "fbxl18. fbxl18 binds to the", "fbxl18 binds to the fq", "binds to the fq motif", "to the fq motif of", "the fq motif of fbxl7", "motif of fbxl7 targeting", "of fbxl7 targeting it", "fbxl7 targeting it for", "targeting it for ubiquitination and", "it for ubiquitination and proteasome", "for ubiquitination and proteasome mediated", "ubiquitination and proteasome mediated degradation", "proteasome mediated degradation counteracting", "mediated degradation counteracting its", "degradation counteracting its pro", "counteracting its pro apoptotic activity", "pro apoptotic activity liu", "apoptotic activity liu et", "activity liu et al.", "liu et al. 2015 .", "et al. 2015 . cell", "al. 2015 . cell cycle", "2015 . cell cycle stage", ". cell cycle stage dependency", "cell cycle stage dependency of", "cycle stage dependency of down", "stage dependency of down regulation", "dependency of down regulation of", "of down regulation of fbxl7", "down regulation of fbxl7 by", "regulation of fbxl7 by fbxl18", "of fbxl7 by fbxl18 is", "fbxl7 by fbxl18 is unknown." ] }, { "record_id": "GLY_000594_1_615", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8854518", "r hsa", "hsa 8854518", "r hsa 8854518" ] }, { "record_id": "GLY_000594_1_615", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "aurka activation", "activation by", "by tpx2", "aurka activation by", "activation by tpx2", "aurka activation by tpx2", "tpx2 binds", "binds to", "to aurora", "aurora kinase", "kinase a", "at centrosomes", "centrosomes and", "and promotes", "promotes its", "its activation", "by facilitating", "facilitating aurka", "aurka active", "active conformation", "conformation and", "and autophosphorylation", "autophosphorylation of", "of the", "the aurka", "aurka threonine", "threonine residue", "residue t288", "bayliss et", "et al.", "al. 2003", "xu et", "al. 2011", "giubettini et", "dodson and", "and bayliss", "bayliss 2012", "2012 .", "tpx2 binds to", "binds to aurora", "to aurora kinase", "aurora kinase a", "a aurka", "aurka at", "at centrosomes and", "centrosomes and promotes", "and promotes its", "promotes its activation", "its activation by", "activation by facilitating", "by facilitating aurka", "facilitating aurka active", "aurka active conformation", "active 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a", "

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in", ".


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a", "motifs.

a number", "

a number of", "number of studies", "of studies have", "studies have been", "have been performed", "been performed to", "performed to test", "to test whether", "test whether ap", "whether ap 2", "ap 2 is", "2 is essential", "is essential for", "essential for all", "for all forms", "all forms of", "forms of clathrin", "endocytosis keyel", "keyel et al", "al 2006", "2006 motely", "motely et al", "al 2003", "2003 huang", "huang et al", "al 2004", "2004 boucrot", "boucrot et al", "al 2010", "2010 henne", "henne et al", "2010 johannessen", "johannessen et al", "2006 gu", "gu et al", "al 2013", "2013 reviewed", "traub 2009", "2009 mcmahon", "mcmahon and boucrot", "boucrot 2011", "2011 . although", ". although depletion", "although depletion of", "depletion of ap", "of ap 2", "ap 2 differentially", "2 differentially affects", "differentially affects the", "affects the endocytosis", "endocytosis of different", "of different cargo", "cargo extensive", "extensive depletion of", "ap 2 through", "2 through rnai", "through rnai reduces", "rnai reduces clathrin", "reduces clathrin coated", "coated pit formation", "pit formation by", "formation by 80", "by 80 90%", "90% and", "and the ccps", "the ccps that", "ccps that do", "that do form", "do form still", "form still contain", "still contain ap", "contain ap 2", "2 highlighting", "highlighting the critcical", "the critcical role", "critcical role of", "role of this", "of this complex", "this complex in", "complex in cme", "cme johannessen", "2006 boucrot", "2010 .


in addition", ".


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a", "based motifs.

a number", "motifs.

a number of", "

a number of studies", "number of studies have", "of studies have been", "studies have been performed", "have been performed to", "been performed to test", "performed to test whether", "to test whether ap", "test whether ap 2", "whether ap 2 is", "ap 2 is essential", "2 is essential for", "is essential for all", "essential for all forms", "for all forms of", "all forms of clathrin", "forms of clathrin mediated", "mediated endocytosis keyel", "endocytosis keyel et", "et al 2006", "2006 motely et", "et al 2003", "2003 huang et", "et al 2004", "2004 boucrot et", "et al 2010", "2010 henne et", "2010 johannessen et", "2006 gu et", "et al 2013", "2013 reviewed in", "in traub 2009", "2009 mcmahon and", "and boucrot 2011", "boucrot 2011 .", "2011 . although depletion", ". although depletion of", "although depletion of ap", "depletion of ap 2", "of ap 2 differentially", "ap 2 differentially affects", "2 differentially affects the", "differentially affects the endocytosis", "affects the endocytosis of", "the endocytosis of different", "endocytosis of different cargo", "different cargo extensive", "cargo extensive depletion", "extensive depletion of ap", "of ap 2 through", "ap 2 through rnai", "2 through rnai reduces", "through rnai reduces clathrin", "rnai reduces clathrin coated", "reduces clathrin coated pit", "clathrin coated pit formation", "coated pit formation by", "pit formation by 80", "formation by 80 90%", "80 90% and", "90% and the", "and the ccps that", "the ccps that do", "ccps that do form", "that do form still", "do form still contain", "form still contain ap", "still contain ap 2", "ap 2 highlighting", "2 highlighting the", "highlighting the critcical role", "the critcical role of", "critcical role of this", "role of this complex", "of this complex in", "this complex in cme", "in cme johannessen", "cme johannessen et", "2006 boucrot et", "al 2010 .


in", "2010 .


in addition to", ".


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"reviewed in traub and bonifacino", "traub and bonifacino 2013", "and bonifacino 2013 .", "2013 . the tetrameric", ". the tetrameric ap", "the tetrameric ap 2 complex", "ap 2 complex first", "2 complex first identified", "complex first identified in", "first identified in early studies", "identified in early studies of", "in early studies of clathrin", "early studies of clathrin mediated", "studies of clathrin mediated endocytosis", "clathrin mediated endocytosis was", "mediated endocytosis was at", "endocytosis was at one", "was at one time thought", "at one time thought to", "one time thought to be", "time thought to be the", "thought to be the primary", "to be the primary clasp", "be the primary clasp protein", "the primary clasp protein involved", "primary clasp protein involved in", "clasp protein involved in cargo", "protein involved in cargo recognition", "involved in cargo recognition at", "in cargo recognition at the", "cargo recognition at the plasma", "recognition at the plasma membrane", "the plasma membrane and", "plasma membrane and indeed", "membrane and indeed plays", "and indeed plays a key", "indeed plays a key role", "plays a key role in", "a key role in the", "key role in the endocytosis", "role in the endocytosis of", "in the endocytosis of cargo", "the endocytosis of cargo carrying", "endocytosis of cargo carrying dileucine", "cargo carrying dileucine or", "carrying dileucine or tyrosine", "dileucine or tyrosine based", "or tyrosine based motifs.

a", "tyrosine based motifs.

a number", "based motifs.

a number of", "motifs.

a number of studies", "

a number of studies have", "number of studies have been", "of studies have been performed", "studies have been performed to", "have been performed to test", "been performed to test whether", "performed to test whether ap", "to test whether ap 2", "test whether ap 2 is", "whether ap 2 is essential", "ap 2 is essential for", "2 is essential for all", "is essential for all forms", "essential for all forms of", "for all forms of clathrin", "all forms of clathrin mediated", "forms of clathrin mediated endocytosis", "clathrin mediated endocytosis keyel", "mediated endocytosis keyel et", "endocytosis keyel et al", "keyel et al 2006", "al 2006 motely", "2006 motely et al", "motely et al 2003", "al 2003 huang", "2003 huang et al", "huang et al 2004", "al 2004 boucrot", "2004 boucrot et al", "boucrot et al 2010", "al 2010 henne", "2010 henne et al", "henne et al 2010", "al 2010 johannessen", "2010 johannessen et al", "johannessen et al 2006", "al 2006 gu", "2006 gu et al", "gu et al 2013", "al 2013 reviewed", "2013 reviewed in traub", "reviewed in traub 2009", "traub 2009 mcmahon", "2009 mcmahon and boucrot", "mcmahon and boucrot 2011", "and boucrot 2011 .", "boucrot 2011 . although", "2011 . although depletion of", ". although depletion of ap", "although depletion of ap 2", "depletion of ap 2 differentially", "of ap 2 differentially affects", "ap 2 differentially affects the", "2 differentially affects the endocytosis", "differentially affects the endocytosis of", "affects the endocytosis of different", "the endocytosis of different cargo", "of different cargo extensive", "different cargo extensive depletion", "cargo extensive depletion of", "extensive depletion of ap 2", "depletion of ap 2 through", "of ap 2 through rnai", "ap 2 through rnai reduces", "2 through rnai reduces clathrin", "through rnai reduces clathrin coated", "rnai reduces clathrin coated pit", "reduces clathrin coated pit formation", "clathrin coated pit formation by", "coated pit formation by 80", "pit formation by 80 90%", "by 80 90% and", "80 90% and the", "90% and the ccps", "and the ccps that do", "the ccps that do form", "ccps that do form still", "that do form still contain", "do form still contain ap", "form still contain ap 2", "contain ap 2 highlighting", "ap 2 highlighting the", "2 highlighting the critcical", "highlighting the critcical role of", "the critcical role of this", "critcical role of this complex", "role of this complex in", "of this complex in cme", "complex in cme johannessen", "in cme johannessen et", "cme johannessen et al", "al 2006 boucrot", "2006 boucrot et al", "et al 2010 .


in", "al 2010 .


in addition", "2010 .


in addition to ap", ".


in addition to ap 2", "to ap 2 a", "ap 2 a wide", "2 a wide range", "a wide range of other", "wide range of other clasps", "range of other clasps including", "of other clasps including proteins", "other clasps including proteins of", "clasps including proteins of the", "including proteins of the beta", "proteins of the beta arrestin", "the beta arrestin stonin", "beta arrestin stonin and", "arrestin stonin and epsin", "and epsin families engage", "epsin families engage sorting", "families engage sorting motifs", "engage sorting motifs in other", "sorting motifs in other cargo", "motifs in other cargo and", "in other cargo and interact", "other cargo and interact either", "cargo and interact either with", "and interact either with clathrin", "either with clathrin ap", "with clathrin ap 2", "clathrin ap 2 or", "ap 2 or each other", "2 or each other to", "or each other to facilitate", "each other to facilitate assembly", "other to facilitate assembly of", "to facilitate assembly of a", "facilitate assembly of a clathin", "assembly of a clathin coated", "of a clathin coated pit", "clathin coated pit reviewed" ] }, { "record_id": "GLY_000594_1_618", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8856828", "r hsa", "hsa 8856828", "r hsa 8856828" ] }, { "record_id": "GLY_000594_1_618", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "clathrin mediated", "mediated endocytosis", "clathrin mediated endocytosis", "is one", "one of", "of a", "a number", "number of", "of process", "process that", "that control", "control the", "the uptake", "uptake of", "of material", "material from", "from the", "the plasma", "plasma membrane", "and leads", "leads to", "to the", "the formation", "formation of", "of clathrin", "clathrin coated", "coated vesicles", "pearse et", "et al", "reviewed in", "in robinson", "mcmahon and", "and boucrot", "kirchhausen et", "2014 .", "cme contributes", "contributes to", "to signal", "signal transduction", "transduction by", "by regulating", "regulating the", "the cell", "cell surface", "surface expression", "expression and", "and signaling", "signaling of", "of receptor", "receptor tyrosine", "tyrosine kinases", "and g", "g protein", "protein coupled", "coupled receptors", "gpcrs .", "most rtks", "rtks exhibit", "exhibit a", "a robust", "robust increase", "increase in", "in internalization", "internalization rate", "rate after", "after binding", "binding specific", "specific ligands", "some rtks", "rtks may", "may also", "also exhibit", "exhibit significant", "significant ligand", "ligand independent", "independent internalization", "in goh", "goh and", "and sorkin", "2013 .", ". cme", "cme controls", "controls rtk", "rtk and", "and gpcr", "gpcr signaling", "signaling by", "by organizing", "organizing signaling", "signaling both", "both within", "within the", "membrane and", "and on", "on endosomes", "in eichel", "eichel et", "garay et", "vieira et", "sorkin and", "and von", "von zastrow", "di fiori", "fiori and", "barbieri et", "2016 .", "cme also", "also contributes", "material such", "such as", "as metabolites", "hormones and", "and other", "other proteins", "proteins from", "the extracellular", "extracellular space", "and regulates", "regulates membrane", "membrane composition", "composition by", "by recycling", "recycling membrane", "membrane components", "components and/or", "and/or targeting", "targeting them", "them for", "for degradation.", "degradation.


clathrin", "


clathrin mediated", "endocytosis involves", "involves initiation", "initiation of", "coated pit", "cargo selection", "coat assembly", "assembly and", "and stabilization", "membrane scission", "scission and", "and vesicle", "vesicle uncoating.", "although for", "for simplicity", "simplicity in", "in this", "this pathway", "the steps", "steps leading", "leading to", "to a", "a mature", "mature ccp", "ccp are", "are represented", "represented in", "in a", "a linear", "linear and", "and temporally", "temporally distinct", "distinct fashion", "a clathrin", "coated vesicle", "vesicle is", "is a", "a highly", "highly heterogeneous", "heterogeneous process", "process and", "and clear", "clear temporal", "temporal boundaries", "boundaries between", "between these", "these processes", "processes may", "may not", "not exist", "see for", "for instance", "instance taylor", "taylor et", "antonescu et", "in kirchhausen", ". cargo", "selection in", "in particular", "particular is", "a critical", "critical aspect", "aspect of", "of the", "mature and", "and stable", "stable ccp", "and many", "many of", "the proteins", "proteins involved", "involved in", "in the", "the initiation", "initiation and", "and maturation", "maturation of", "a ccp", "ccp contribute", "contribute to", "to cargo", "selection and", "and are", "are themselves", "themselves stabilized", "stabilized upon", "upon incorporation", "incorporation of", "of cargo", "cargo into", "into the", "the nascent", "nascent vesicle", "2011 .



although", ".



although the", "the clathrin", "clathrin triskelion", "triskelion was", "was identified", "identified early", "early as", "as a", "a major", "major component", "component of", "the coated", "clathrin does", "does not", "not bind", "bind directly", "directly to", "to membranes", "membranes or", "or to", "the endocytosed", "endocytosed cargo.", "vesicle formation", "formation instead", "instead relies", "relies on", "on many", "many proteins", "proteins and", "and adaptors", "adaptors that", "that can", "can bind", "bind the", "and interact", "interact with", "with cargo", "cargo molecules.", "molecules. cargo", "selection depends", "depends on", "on the", "the recognition", "recognition of", "of endocytic", "endocytic signals", "signals in", "in cytoplasmic", "cytoplasmic tails", "tails of", "the cargo", "cargo proteins", "proteins by", "by adaptors", "that interact", "with components", "components of", "the vesicle's", "vesicle's inner", "inner coat.", "the classic", "classic adaptor", "adaptor for", "for clathrin", "vesicles is", "is the", "the tetrameric", "tetrameric ap", "ap 2", "2 complex", "which along", "along with", "with clathrin", "clathrin was", "the coat.", "some cargo", "cargo indeed", "indeed bind", "to ap", "but subsequent", "subsequent work", "work has", "has revealed", "revealed a", "a large", "large family", "family of", "of proteins", "proteins collectively", "collectively known", "known as", "as clasps", "associated sorting", "sorting proteins", "that mediate", "mediate the", "the recruitment", "recruitment of", "of diverse", "diverse cargo", "the emerging", "emerging clathrin", "in traub", "traub and", "and bonifacino", "of these", "these clasp", "clasp proteins", "proteins themselves", "themselves interact", "with ap", "2 and", "and clathrin", "coordinating cargo", "cargo recruitment", "recruitment with", "with coat", "coat formation", "schmid et", "edeling et", "


initiation of", "of ccp", "ccp formation", "formation is", "is also", "also influenced", "influenced by", "by lipid", "lipid composition", "regulated by", "by clathrin", "clathrin associated", "associated phosphatases", "phosphatases and", "and kinases", "in picas", "picas et", ". the", "membrane is", "is enriched", "enriched in", "in pi", "pi 4", "4 5", "5 p2.", "in initiating", "initiating clathrin", "pit formation", "formation bind", "bind to", "to pi", "5 p2", "p2 and", "and induce", "induce membrane", "membrane curvature", "curvature through", "through their", "their bar", "bar domains", "in mcmahon", "daumke et", "epsin also", "to early", "early membrane", "through its", "its epsin", "epsin n", "n terminal", "terminal homology", "which promotes", "promotes membrane", "curvature by", "by inserting", "inserting into", "the lipid", "lipid bilayer", "ford et", "2002 .", ".

following", "

following initiation", "some ccps", "ccps progress", "progress to", "to formation", "of vesicles", "while others", "others undergo", "undergo disassembly", "disassembly at", "at the", "surface without", "without producing", "producing vesicles", "ehrlich et", "loerke et", "aguet et", "2011 .", "the assembly", "stabilization of", "of nascent", "nascent ccps", "ccps is", "is regulated", "by several", "several proteins", "and lipids", "mettlen et", "2011 .


maturation", ".


maturation of", "is accompanied", "accompanied by", "by further", "further changes", "changes in", "composition of", "the membrane", "and increased", "increased membrane", "promoted by", "by the", "of n", "n bar", "bar domain", "domain containing", "containing proteins", "in daumke", "ferguson and", "and de", "de camilli", ". some", "some n", "proteins also", "also contribute", "the large", "large gtpase", "gtpase dynamin", "which is", "is responsible", "responsible for", "for scission", "scission of", "the mature", "mature vesicle", "vesicle from", "koh et", "lundmark and", "and carlsson", "soulet et", "david et", "owen et", "shupliakov et", "ferguson et", "posor et", "chappie et", "shnyrova et", "in mettlen", "after vesicle", "vesicle scission", "clathrin coat", "coat is", "is dissociated", "dissociated from", "the new", "new vesicle", "vesicle by", "the atpase", "atpase hspa8", "also known", "as hsc70", "and its", "its dnaj", "dnaj cofactor", "cofactor auxilin", "priming the", "the vesicle", "vesicle for", "for fusion", "fusion with", "with a", "a subsequent", "subsequent endocytic", "endocytic compartment", "compartment and", "and releasing", "releasing clathrin", "clathrin for", "for reuse", "sousa and", "and laufer", "2015 .", "endocytosis cme", "cme is", "is one of", "one of a", "of a number", "a number of", "number of process", "of process that", "process that control", "that control the", "control the uptake", "the uptake of", "uptake of material", "of material from", "material from the", "from the plasma", "the plasma membrane", "and leads to", "leads to the", "to the formation", "the formation of", "formation of clathrin", "of clathrin coated", "clathrin coated vesicles", "vesicles pearse", "pearse et al", "al 1975", "1975 reviewed", "reviewed in robinson", "robinson 2015", "2015 mcmahon", "mcmahon and boucrot", "boucrot 2011", "2011 kirchhausen", "kirchhausen et al", "al 2014", "cme contributes to", "contributes to signal", "to signal transduction", "signal transduction by", "transduction by regulating", "by regulating the", "regulating the cell", "the cell surface", "cell surface expression", "surface expression and", "expression and signaling", "and signaling of", "signaling of receptor", "of receptor tyrosine", "receptor tyrosine kinases", "kinases rtks", "rtks and", "and g protein", "g protein coupled", "protein coupled receptors", "receptors gpcrs", ". most", "most rtks exhibit", "rtks exhibit a", "exhibit a robust", "a robust increase", "robust increase in", "increase in internalization", "in internalization rate", "internalization rate after", "rate after binding", "after binding specific", "binding specific ligands", "ligands however", "however some", "some rtks may", "rtks may also", "may also exhibit", "also exhibit significant", "exhibit significant ligand", "significant ligand independent", "ligand independent internalization", "internalization reviewed", "reviewed in goh", "in goh and", "goh and sorkin", "sorkin 2013", "2013 . cme", ". cme controls", "cme controls rtk", "controls rtk and", "rtk and gpcr", "and gpcr signaling", "gpcr signaling by", "signaling by organizing", "by organizing signaling", "organizing signaling both", "signaling both within", "both within the", "within the plasma", "plasma membrane and", "membrane and on", "and on endosomes", "endosomes reviewed", "reviewed in eichel", "in eichel et", "eichel et al", "al 2016", "2016 garay", "garay et al", "al 2015", "2015 vieira", "vieira et al", "al 1996", "1996 sorkin", "sorkin and von", "and von zastrow", "zastrow 2014", "2014 di", "di fiori and", "fiori and von", "2014 barbieri", "barbieri et al", "2016 . cme", ". cme also", "cme also contributes", "also contributes to", "contributes to the", "to the uptake", "of material such", "material such as", "such as metabolites", "metabolites hormones", "hormones and other", "and other proteins", "other proteins from", "proteins from the", "from the extracellular", "the extracellular space", "space and", "and regulates membrane", "regulates membrane composition", "membrane composition by", "composition by recycling", "by recycling membrane", "recycling membrane components", "membrane components and/or", "components and/or targeting", "and/or targeting them", "targeting them for", "them for degradation.", "for degradation.


clathrin", "degradation.


clathrin mediated", "


clathrin mediated endocytosis", "mediated endocytosis involves", "endocytosis involves initiation", "involves initiation of", "initiation of clathrin", "clathrin coated pit", "pit ccp", "formation cargo", "selection coat", "coat assembly and", "assembly and stabilization", "stabilization membrane", "membrane scission and", "scission and vesicle", "and vesicle uncoating.", "uncoating. although", "although for simplicity", "for simplicity in", "simplicity in this", "in this pathway", "pathway the", "the steps leading", "steps leading to", "leading to a", "to a mature", "a mature ccp", "mature ccp are", "ccp are represented", "are represented in", "represented in a", "in a linear", "a linear and", "linear and temporally", "and temporally distinct", "temporally distinct fashion", "fashion the", "formation of a", "of a clathrin", "a clathrin coated", "clathrin coated vesicle", "coated vesicle is", "vesicle is a", "is a highly", "a highly heterogeneous", "highly heterogeneous process", "heterogeneous process and", "process and clear", "and clear temporal", "clear temporal boundaries", "temporal boundaries between", "boundaries between these", "between these processes", "these processes may", "processes may not", "may not exist", "exist see", "see for instance", "for instance taylor", "instance taylor et", "taylor et al", "al 2011", "2011 antonescu", "antonescu et al", "2011 reviewed", "reviewed in kirchhausen", "in kirchhausen et", "2014 . cargo", ". cargo selection", "cargo selection in", "selection in particular", "in particular is", "particular is a", "is a critical", "a critical aspect", "critical aspect of", "aspect of the", "of the formation", "of a mature", "a mature and", "mature and stable", "and stable ccp", "ccp and", "and many of", "many of the", "of the proteins", "the proteins involved", "proteins involved in", "involved in the", "in the initiation", "the initiation and", "initiation and maturation", "and maturation of", "maturation of a", "of a ccp", "a ccp contribute", "ccp contribute to", "contribute to cargo", "to cargo selection", "cargo selection and", "selection and are", "and are themselves", "are themselves stabilized", "themselves stabilized upon", "stabilized upon incorporation", "upon incorporation of", "incorporation of cargo", "of cargo into", "cargo into the", "into the nascent", "the nascent vesicle", "vesicle reviewed", "2014 mcmahon", "2011 .



although the", ".



although the clathrin", "the clathrin triskelion", "clathrin triskelion was", "triskelion was identified", "was identified early", "identified early as", "early as a", "as a major", "a major component", "major component of", "component of the", "of the coated", "the coated vesicles", "vesicles clathrin", "clathrin does not", "does not bind", "not bind directly", "bind directly to", "directly to membranes", "to membranes or", "membranes or to", "or to the", "to the endocytosed", "the endocytosed cargo.", "cargo. vesicle", "vesicle formation instead", "formation instead relies", "instead relies on", "relies on many", "on many proteins", "many proteins and", "proteins and adaptors", "and adaptors that", "adaptors that can", "that can bind", "can bind the", "bind the plasma", "membrane and interact", "and interact with", "interact with cargo", "with cargo molecules.", "cargo molecules. cargo", "molecules. cargo selection", "cargo selection depends", "selection depends on", "depends on the", "on the recognition", "the recognition of", "recognition of endocytic", "of endocytic signals", "endocytic signals in", "signals in cytoplasmic", "in cytoplasmic tails", "cytoplasmic tails of", "tails of the", "of the cargo", "the cargo proteins", "cargo proteins by", "proteins by adaptors", "by adaptors that", "adaptors that interact", "that interact with", "interact with components", "with components of", "components of the", "of the vesicle's", "the vesicle's inner", "vesicle's inner coat.", "coat. the", "the classic adaptor", "classic adaptor for", "adaptor for clathrin", "for clathrin coated", "coated vesicles is", "vesicles is the", "is the tetrameric", "the tetrameric ap", "tetrameric ap 2", "ap 2 complex", "complex which", "which along with", "along with clathrin", "with clathrin was", "clathrin was identified", "of the coat.", "coat. some", "some cargo indeed", "cargo indeed bind", "indeed bind directly", "directly to ap", "to ap 2", "2 but", "but subsequent work", "subsequent work has", "work has revealed", "has revealed a", "revealed a large", "a large family", "large family of", "family of proteins", "of proteins collectively", "proteins collectively known", "collectively known as", "known as clasps", "clasps clathrin", "associated sorting proteins", "proteins that", "that mediate the", "mediate the recruitment", "the recruitment of", "recruitment of diverse", "of diverse cargo", "diverse cargo into", "into the emerging", "the emerging clathrin", "emerging clathrin coated", "vesicles reviewed", "reviewed in traub", "in traub and", "traub and bonifacino", "bonifacino 2013", ". many", "many of these", "of these clasp", "these clasp proteins", "clasp proteins themselves", "proteins themselves interact", "themselves interact with", "interact with ap", "with ap 2", "ap 2 and", "2 and clathrin", "clathrin coordinating", "coordinating cargo recruitment", "cargo recruitment with", "recruitment with coat", "with coat formation", "formation schmid", "schmid et al", "al 2006", "2006 edeling", "edeling et al", "2006 reviewed", "2013 kirchhausen", ".


initiation", "


initiation of ccp", "of ccp formation", "ccp formation is", "formation is also", "is also influenced", "also influenced by", "influenced by lipid", "by lipid composition", "composition regulated", "regulated by clathrin", "by clathrin associated", "clathrin associated phosphatases", "associated phosphatases and", "phosphatases and kinases", "kinases reviewed", "reviewed in picas", "in picas et", "picas et al", "2016 . the", ". the plasma", "plasma membrane is", "membrane is enriched", "is enriched in", "enriched in pi", "in pi 4", "pi 4 5", "4 5 p2.", "p2. many", "involved in initiating", "in initiating clathrin", "initiating clathrin coated", "coated pit formation", "pit formation bind", "formation bind to", "bind to pi", "to pi 4", "4 5 p2", "5 p2 and", "p2 and induce", "and induce membrane", "induce membrane curvature", "membrane curvature through", "curvature through their", "through their bar", "their bar domains", "domains reviewed", "reviewed in mcmahon", "in mcmahon and", "2011 daumke", "daumke et al", ". epsin", "epsin also contributes", "contributes to early", "to early membrane", "early membrane curvature", "curvature through its", "through its epsin", "its epsin n", "epsin n terminal", "n terminal homology", "homology enth", "enth domain", "domain which", "which promotes membrane", "promotes membrane curvature", "membrane curvature by", "curvature by inserting", "by inserting into", "inserting into the", "into the lipid", "the lipid bilayer", "bilayer ford", "ford et al", "al 2002", "2002 .

following", ".

following initiation", "initiation some", "some ccps progress", "ccps progress to", "progress to formation", "to formation of", "formation of vesicles", "vesicles while", "while others undergo", "others undergo disassembly", "undergo disassembly at", "disassembly at the", "at the cell", "cell surface without", "surface without producing", "without producing vesicles", "vesicles ehrlich", "ehrlich et al", "al 2004", "2004 loerke", "loerke et al", "al 2009", "2009 loerke", "2011 aguet", "aguet et al", "al 2013", "2013 taylor", "2011 . the", ". the assembly", "the assembly and", "and stabilization of", "stabilization of nascent", "of nascent ccps", "nascent ccps is", "ccps is regulated", "is regulated by", "regulated by several", "by several proteins", "several proteins and", "proteins and lipids", "lipids mettlen", "mettlen et al", "2009 antonescu", "2011 .


maturation of", ".


maturation of the", "of the emerging", "vesicle is accompanied", "is accompanied by", "accompanied by further", "by further changes", "further changes in", "changes in the", "in the lipid", "the lipid composition", "lipid composition of", "composition of the", "of the membrane", "the membrane and", "membrane and increased", "and increased membrane", "increased membrane curvature", "curvature promoted", "promoted by the", "by the recruitment", "recruitment of n", "of n bar", "n bar domain", "bar domain containing", "domain containing proteins", "proteins reviewed", "reviewed in daumke", "in daumke et", "2014 ferguson", "ferguson and de", "and de camilli", "camilli 2012", "2012 picas", "2016 . some", ". some n", "some n bar", "containing proteins also", "proteins also contribute", "also contribute to", "contribute to the", "to the recruitment", "recruitment of the", "of the large", "the large gtpase", "large gtpase dynamin", "dynamin which", "which is responsible", "is responsible for", "responsible for scission", "for scission of", "scission of the", "of the mature", "the mature vesicle", "mature vesicle from", "vesicle from the", "membrane koh", "koh et al", "al 2007", "2007 lundmark", "lundmark and carlsson", "carlsson 2003", "2003 soulet", "soulet et al", "al 2005", "2005 david", "david et al", "1996 owen", "owen et al", "al 1998", "1998 shupliakov", "shupliakov et al", "al 1997", "1997 taylor", "2011 ferguson", "ferguson et al", "2009 aguet", "2013 posor", "posor et al", "2013 chappie", "chappie et al", "al 2010", "2010 shnyrova", "shnyrova et al", "2013 reviewed", "reviewed in mettlen", "in mettlen et", "2009 daumke", ". after", "after vesicle scission", "scission the", "the clathrin coat", "clathrin coat is", "coat is dissociated", "is dissociated from", "dissociated from the", "from the new", "the new vesicle", "new vesicle by", "vesicle by the", "by the atpase", "the atpase hspa8", "hspa8 also", "also known as", "known as hsc70", "hsc70 and", "and its dnaj", "its dnaj cofactor", "dnaj cofactor auxilin", "auxilin priming", "priming the vesicle", "the vesicle for", "vesicle for fusion", "for fusion with", "fusion with a", "with a subsequent", "a subsequent endocytic", "subsequent endocytic compartment", "endocytic compartment and", "compartment and releasing", "and releasing clathrin", "releasing clathrin for", "clathrin for reuse", "2011 sousa", "sousa and laufer", "laufer 2015", "mediated endocytosis cme", "cme is one", "is one of a", "one of a number", "of a number of", "a number of process", "number of process that", "of process that control", "process that control the", "that control the uptake", "control the uptake of", "the uptake of material", "uptake of material from", "of material from the", "material from the plasma", "from the plasma membrane", "membrane and leads", "and leads to the", "leads to the formation", "to the formation of", "the formation of clathrin", "formation of clathrin coated", "of clathrin coated vesicles", "coated vesicles pearse", "vesicles pearse et", "et al 1975", "1975 reviewed in", "in robinson 2015", "2015 mcmahon and", "and boucrot 2011", "2011 kirchhausen et", "et al 2014", "al 2014 .", "2014 . cme", ". cme contributes", "cme contributes to signal", "contributes to signal transduction", "to signal transduction by", "signal transduction by regulating", "transduction by regulating the", "by regulating the cell", "regulating the cell surface", "the cell surface expression", "cell surface expression and", "surface expression and signaling", "expression and signaling of", "and signaling of receptor", "signaling of receptor tyrosine", "of receptor tyrosine kinases", "tyrosine kinases rtks", "rtks and g", "and g protein coupled", "g protein coupled receptors", "coupled receptors gpcrs", "receptors gpcrs .", "gpcrs . most", ". most rtks", "most rtks exhibit a", "rtks exhibit a robust", "exhibit a robust increase", "a robust increase in", "robust increase in internalization", "increase in internalization rate", "in internalization rate after", "internalization rate after binding", "rate after binding specific", "after binding specific ligands", "specific ligands however", "however some rtks", "some rtks may also", "rtks may also exhibit", "may also exhibit significant", "also exhibit significant ligand", "exhibit significant ligand independent", "significant ligand independent internalization", "independent internalization reviewed", "internalization reviewed in", "reviewed in goh and", "in goh and sorkin", "and sorkin 2013", "sorkin 2013 .", "2013 . cme controls", ". cme controls rtk", "cme controls rtk and", "controls rtk and gpcr", "rtk and gpcr signaling", "and gpcr signaling by", "gpcr signaling by organizing", "signaling by organizing signaling", "by organizing signaling both", "organizing signaling both within", "signaling both within the", "both within the plasma", "within the plasma membrane", "the plasma membrane and", "plasma membrane and on", "membrane and on endosomes", "on endosomes reviewed", "endosomes reviewed in", "reviewed in eichel et", "in eichel et al", "et al 2016", "2016 garay et", "et al 2015", "2015 vieira et", "et al 1996", "1996 sorkin and", "sorkin and von zastrow", "von zastrow 2014", "2014 di fiori", "di fiori and von", "fiori and von zastrow", "2014 barbieri et", "al 2016 .", "2016 . cme also", ". cme also contributes", "cme also contributes to", "also contributes to the", "contributes to the uptake", "to the uptake of", "uptake of material such", "of material such as", "material such as metabolites", "as metabolites hormones", "metabolites hormones and", "hormones and other proteins", "and other proteins from", "other proteins from the", "proteins from the extracellular", "from the extracellular space", "extracellular space and", "space and regulates", "and regulates membrane composition", "regulates membrane composition by", "membrane composition by recycling", "composition by recycling membrane", "by recycling membrane components", "recycling membrane components and/or", "membrane components and/or targeting", "components and/or targeting them", "and/or targeting them for", "targeting them for degradation.", "them for degradation.


clathrin", "for degradation.


clathrin mediated", "degradation.


clathrin mediated endocytosis", "


clathrin mediated endocytosis involves", "mediated endocytosis involves initiation", "endocytosis involves initiation of", "involves initiation of clathrin", "initiation of clathrin coated", "of clathrin coated pit", "coated pit ccp", "formation cargo selection", "cargo selection coat", "selection coat assembly", "coat assembly and stabilization", "and stabilization membrane", "stabilization membrane scission", "membrane scission and vesicle", "scission and vesicle uncoating.", "vesicle uncoating. although", "uncoating. although for", "although for simplicity in", "for simplicity in this", "simplicity in this pathway", "this pathway the", "pathway the steps", "the steps leading to", "steps leading to a", "leading to a mature", "to a mature ccp", "a mature ccp are", "mature ccp are represented", "ccp are represented in", "are represented in a", "represented in a linear", "in a linear and", "a linear and temporally", "linear and temporally distinct", "and temporally distinct fashion", "distinct fashion the", "fashion the formation", "the formation of a", "formation of a clathrin", "of a clathrin coated", "a clathrin coated vesicle", "clathrin coated vesicle is", "coated vesicle is a", "vesicle is a highly", "is a highly heterogeneous", "a highly heterogeneous process", "highly heterogeneous process and", "heterogeneous process and clear", "process and clear temporal", "and clear temporal boundaries", "clear temporal boundaries between", "temporal boundaries between these", "boundaries between these processes", "between these processes may", "these processes may not", "processes may not exist", "not exist see", "exist see for", "see for instance taylor", "for instance taylor et", "instance taylor et al", "et al 2011", "2011 antonescu et", "2011 reviewed in", "reviewed in kirchhausen et", "in kirchhausen et al", "2014 . cargo selection", ". cargo selection in", "cargo selection in particular", "selection in particular is", "in particular is a", "particular is a critical", "is a critical aspect", "a critical aspect of", "critical aspect of the", "aspect of the formation", "of the formation of", "formation of a mature", "of a mature and", "a mature and stable", "mature and stable ccp", "stable ccp and", "ccp and many", "and many of the", "many of the proteins", "of the proteins involved", "the proteins involved in", "proteins involved in the", "involved in the initiation", "in the initiation and", "the initiation and maturation", "initiation and maturation of", "and maturation of a", "maturation of a ccp", "of a ccp contribute", "a ccp contribute to", "ccp contribute to cargo", "contribute to cargo selection", "to cargo selection and", "cargo selection and are", "selection and are themselves", "and are themselves stabilized", "are themselves stabilized upon", "themselves stabilized upon incorporation", "stabilized upon incorporation of", "upon incorporation of cargo", "incorporation of cargo into", "of cargo into the", "cargo into the nascent", "into the nascent vesicle", "nascent vesicle reviewed", "vesicle reviewed in", "2014 mcmahon and", "boucrot 2011 .



although", "2011 .



although the clathrin", ".



although the clathrin triskelion", "the clathrin triskelion was", "clathrin triskelion was identified", "triskelion was identified early", "was identified early as", "identified early as a", "early as a major", "as a major component", "a major component of", "major component of the", "component of the coated", "of the coated vesicles", "coated vesicles clathrin", "vesicles clathrin does", "clathrin does not bind", "does not bind directly", "not bind directly to", "bind directly to membranes", "directly to membranes or", "to membranes or to", "membranes or to the", "or to the endocytosed", "to the endocytosed cargo.", "endocytosed cargo. vesicle", "cargo. vesicle formation", "vesicle formation instead relies", "formation instead relies on", "instead relies on many", "relies on many proteins", "on many proteins and", "many proteins and adaptors", "proteins and adaptors that", "and adaptors that can", "adaptors that can bind", "that can bind the", "can bind the plasma", "bind the plasma membrane", "plasma membrane and interact", "membrane and interact with", "and interact with cargo", "interact with cargo molecules.", "with cargo molecules. cargo", "cargo molecules. cargo selection", "molecules. cargo selection depends", "cargo selection depends on", "selection depends on the", "depends on the recognition", "on the recognition of", "the recognition of endocytic", "recognition of endocytic signals", "of endocytic signals in", "endocytic signals in cytoplasmic", "signals in cytoplasmic tails", "in cytoplasmic tails of", "cytoplasmic tails of the", "tails of the cargo", "of the cargo proteins", "the cargo proteins by", "cargo proteins by adaptors", "proteins by adaptors that", "by adaptors that interact", "adaptors that interact with", "that interact with components", "interact with components of", "with components of the", "components of the vesicle's", "of the vesicle's inner", "the vesicle's inner coat.", "inner coat. the", "coat. the classic", "the classic adaptor for", "classic adaptor for clathrin", "adaptor for clathrin coated", "for clathrin coated vesicles", "clathrin coated vesicles is", "coated vesicles is the", "vesicles is the tetrameric", "is the tetrameric ap", "the tetrameric ap 2", "tetrameric ap 2 complex", "2 complex which", "complex which along", "which along with clathrin", "along with clathrin was", "with clathrin was identified", "clathrin was identified early", "component of the coat.", "the coat. some", "coat. some cargo", "some cargo indeed bind", "cargo indeed bind directly", "indeed bind directly to", "bind directly to ap", "directly to ap 2", "ap 2 but", "2 but subsequent", "but subsequent work has", "subsequent work has revealed", "work has revealed a", "has revealed a large", "revealed a large family", "a large family of", "large family of proteins", "family of proteins collectively", "of proteins collectively known", "proteins collectively known as", "collectively known as clasps", "as clasps clathrin", "clathrin associated sorting", "sorting proteins that", "proteins that mediate", "that mediate the recruitment", "mediate the recruitment of", "the recruitment of diverse", "recruitment of diverse cargo", "of diverse cargo into", "diverse cargo into the", "cargo into the emerging", "into the emerging clathrin", "the emerging clathrin coated", "emerging clathrin coated vesicles", "coated vesicles reviewed", "vesicles reviewed in", "reviewed in traub and", "in traub and bonifacino", "and bonifacino 2013", "bonifacino 2013 .", "2013 . many", ". many of", "many of these clasp", "of these clasp proteins", "these clasp proteins themselves", "clasp proteins themselves interact", "proteins themselves interact with", "themselves interact with ap", "interact with ap 2", "with ap 2 and", "ap 2 and clathrin", "and clathrin coordinating", "clathrin coordinating cargo", "coordinating cargo recruitment with", "cargo recruitment with coat", "recruitment with coat formation", "coat formation schmid", "formation schmid et", "et al 2006", "2006 edeling et", "2006 reviewed in", "2013 kirchhausen et", "2014 .


initiation", ".


initiation of", "


initiation of ccp formation", "of ccp formation is", "ccp formation is also", "formation is also influenced", "is also influenced by", "also influenced by lipid", "influenced by lipid composition", "lipid composition regulated", "composition regulated by", "regulated by clathrin associated", "by clathrin associated phosphatases", "clathrin associated phosphatases and", "associated phosphatases and kinases", "and kinases reviewed", "kinases reviewed in", "reviewed in picas et", "in picas et al", "2016 . the plasma", ". the plasma membrane", "the plasma membrane is", "plasma membrane is enriched", "membrane is enriched in", "is enriched in pi", "enriched in pi 4", "in pi 4 5", "pi 4 5 p2.", "5 p2. many", "p2. many of", "proteins involved in initiating", "involved in initiating clathrin", "in initiating clathrin coated", "initiating clathrin coated pit", "clathrin coated pit formation", "coated pit formation bind", "pit formation bind to", "formation bind to pi", "bind to pi 4", "to pi 4 5", "pi 4 5 p2", "4 5 p2 and", "5 p2 and induce", "p2 and induce membrane", "and induce membrane curvature", "induce membrane curvature through", "membrane curvature through their", "curvature through their bar", "through their bar domains", "bar domains reviewed", "domains reviewed in", "reviewed in mcmahon and", "in mcmahon and boucrot", "2011 daumke et", "2014 . epsin", ". epsin also", "epsin also contributes to", "also contributes to early", "contributes to early membrane", "to early membrane curvature", "early membrane curvature through", "membrane curvature through its", "curvature through its epsin", "through its epsin n", "its epsin n terminal", "epsin n terminal homology", "terminal homology enth", "domain which promotes", "which promotes membrane curvature", "promotes membrane curvature by", "membrane curvature by inserting", "curvature by inserting into", "by inserting into the", "inserting into the lipid", "into the lipid bilayer", "lipid bilayer ford", "bilayer ford et", "et al 2002", "al 2002 .", "2002 .

following initiation", "

following initiation some", "initiation some ccps", "some ccps progress to", "ccps progress to formation", "progress to formation of", "to formation of vesicles", "of vesicles while", "vesicles while others", "while others undergo disassembly", "others undergo disassembly at", "undergo disassembly at the", "disassembly at the cell", "at the cell surface", "the cell surface without", "cell surface without producing", "surface without producing vesicles", "producing vesicles ehrlich", "vesicles ehrlich et", "et al 2004", "2004 loerke et", "et al 2009", "2009 loerke et", "2011 aguet et", "et al 2013", "2013 taylor et", "al 2011 .", "2011 . the assembly", ". the assembly and", "the assembly and stabilization", "assembly and stabilization of", "and stabilization of nascent", "stabilization of nascent ccps", "of nascent ccps is", "nascent ccps is regulated", "ccps is regulated by", "is regulated by several", "regulated by several proteins", "by several proteins and", "several proteins and lipids", "and lipids mettlen", "lipids mettlen et", "2009 antonescu et", "al 2011 .


maturation", "2011 .


maturation of the", ".


maturation of the emerging", "of the emerging clathrin", "emerging clathrin coated vesicle", "coated vesicle is accompanied", "vesicle is accompanied by", "is accompanied by further", "accompanied by further changes", "by further changes in", "further changes in the", "changes in the lipid", "in the lipid composition", "the lipid composition of", "lipid composition of the", "composition of the membrane", "of the membrane and", "the membrane and increased", "membrane and increased membrane", "and increased membrane curvature", "membrane curvature promoted", "curvature promoted by", "promoted by the recruitment", "by the recruitment of", "the recruitment of n", "recruitment of n bar", "of n bar domain", "n bar domain containing", "bar domain containing proteins", "containing proteins reviewed", "proteins reviewed in", "reviewed in daumke et", "in daumke et al", "2014 ferguson and", "ferguson and de camilli", "de camilli 2012", "2012 picas et", "2016 . some n", ". some n bar", "some n bar domain", "domain containing proteins also", "containing proteins also contribute", "proteins also contribute to", "also contribute to the", "contribute to the recruitment", "to the recruitment of", "the recruitment of the", "recruitment of the large", "of the large gtpase", "the large gtpase dynamin", "gtpase dynamin which", "dynamin which is", "which is responsible for", "is responsible for scission", "responsible for scission of", "for scission of the", "scission of the mature", "of the mature vesicle", "the mature vesicle from", "mature vesicle from the", "vesicle from the plasma", "plasma membrane koh", "membrane koh et", "et al 2007", "2007 lundmark and", "and carlsson 2003", "2003 soulet et", "et al 2005", "2005 david et", "1996 owen et", "et al 1998", "1998 shupliakov et", "et al 1997", "1997 taylor et", "2011 ferguson et", "2009 aguet et", "2013 posor et", "2013 chappie et", "et al 2010", "2010 shnyrova et", "2013 reviewed in", "reviewed in mettlen et", "in mettlen et al", "2009 daumke et", "2014 . after", ". after vesicle", "vesicle scission the", "scission the clathrin", "the clathrin coat is", "clathrin coat is dissociated", "coat is dissociated from", "is dissociated from the", "dissociated from the new", "from the new vesicle", "the new vesicle by", "new vesicle by the", "vesicle by the atpase", "by the atpase hspa8", "atpase hspa8 also", "hspa8 also known", "also known as hsc70", "as hsc70 and", "hsc70 and its", "and its dnaj cofactor", "its dnaj cofactor auxilin", "cofactor auxilin priming", "auxilin priming the", "priming the vesicle for", "the vesicle for fusion", "vesicle for fusion with", "for fusion with a", "fusion with a subsequent", "with a subsequent endocytic", "a subsequent endocytic compartment", "subsequent endocytic compartment and", "endocytic compartment and releasing", "compartment and releasing clathrin", "and releasing clathrin for", "releasing clathrin for reuse", "reuse reviewed", "2011 sousa and", "and laufer 2015", "laufer 2015 .", "clathrin mediated endocytosis cme", "endocytosis cme is", "cme is one of", "is one of a number", "one of a number of", "of a number of process", "a number of process that", "number of process that control", "of process that control the", "process that control the uptake", "that control the uptake of", "control the uptake of material", "the uptake of material from", "uptake of material from the", "of material from the plasma", "material from the plasma membrane", "plasma membrane and leads", "membrane and leads to", "and leads to the formation", "leads to the formation of", "to the formation of clathrin", "the formation of clathrin coated", "formation of clathrin coated vesicles", "clathrin coated vesicles pearse", "coated vesicles pearse et", "vesicles pearse et al", "pearse et al 1975", "al 1975 reviewed", "1975 reviewed in robinson", "reviewed in robinson 2015", "robinson 2015 mcmahon", "2015 mcmahon and boucrot", "mcmahon and boucrot 2011", "boucrot 2011 kirchhausen", "2011 kirchhausen et al", "kirchhausen et al 2014", "et al 2014 .", "2014 . cme contributes", ". cme contributes to", "cme contributes to signal transduction", "contributes to signal transduction by", "to signal transduction by regulating", "signal transduction by regulating the", "transduction by regulating the cell", "by regulating the cell surface", "regulating the cell surface expression", "the cell surface expression and", "cell surface expression and signaling", "surface expression and signaling of", "expression and signaling of receptor", "and signaling of receptor tyrosine", "signaling of receptor tyrosine kinases", "receptor tyrosine kinases rtks", "kinases rtks and", "rtks and g protein", "and g protein coupled receptors", "protein coupled receptors gpcrs", "coupled receptors gpcrs .", "gpcrs . most rtks", ". most rtks exhibit", "most rtks exhibit a robust", "rtks exhibit a robust increase", "exhibit a robust increase in", "a robust increase in internalization", "robust increase in internalization rate", "increase in internalization rate after", "in internalization rate after binding", "internalization rate after binding specific", "rate after binding specific ligands", "binding specific ligands however", "ligands however some", "however some rtks may", "some rtks may also exhibit", "rtks may also exhibit significant", "may also exhibit significant ligand", "also exhibit significant ligand independent", "exhibit significant ligand independent internalization", "ligand independent internalization reviewed", "independent internalization reviewed in", "internalization reviewed in goh", "reviewed in goh and sorkin", "goh and sorkin 2013", "and sorkin 2013 .", "sorkin 2013 . cme", "2013 . cme controls rtk", ". cme controls rtk and", "cme controls rtk and gpcr", "controls rtk and gpcr signaling", "rtk and gpcr signaling by", "and gpcr signaling by organizing", "gpcr signaling by organizing signaling", "signaling by organizing signaling both", "by organizing signaling both within", "organizing signaling both within the", "signaling both within the plasma", "both within the plasma membrane", "within the plasma membrane and", "the plasma membrane and on", "plasma membrane and on endosomes", "and on endosomes reviewed", "on endosomes reviewed in", "endosomes reviewed in eichel", "reviewed in eichel et al", "eichel et al 2016", "al 2016 garay", "2016 garay et al", "garay et al 2015", "al 2015 vieira", "2015 vieira et al", "vieira et al 1996", "al 1996 sorkin", "1996 sorkin and von", "and von zastrow 2014", "zastrow 2014 di", "2014 di fiori and", "di fiori and von zastrow", "zastrow 2014 barbieri", "2014 barbieri et al", "barbieri et al 2016", "et al 2016 .", "al 2016 . cme", "2016 . cme also contributes", ". cme also contributes to", "cme also contributes to the", "also contributes to the uptake", "contributes to the uptake of", "to the uptake of material", "the uptake of material such", "uptake of material such as", "of material such as metabolites", "such as metabolites hormones", "as metabolites hormones and", "metabolites hormones and other", "hormones and other proteins from", "and other proteins from the", "other proteins from the extracellular", "proteins from the extracellular space", "the extracellular space and", "extracellular space and regulates", "space and regulates membrane", "and regulates membrane composition by", "regulates membrane composition by recycling", "membrane composition by recycling membrane", "composition by recycling membrane components", "by recycling membrane components and/or", "recycling membrane components and/or targeting", "membrane components and/or targeting them", "components and/or targeting them for", "and/or targeting them for degradation.", "targeting them for degradation.


clathrin", "them for degradation.


clathrin mediated", "for degradation.


clathrin mediated endocytosis", "degradation.


clathrin mediated endocytosis involves", "


clathrin mediated endocytosis involves initiation", "mediated endocytosis involves initiation of", "endocytosis involves initiation of clathrin", "involves initiation of clathrin coated", "initiation of clathrin coated pit", "clathrin coated pit ccp", "pit ccp formation", "ccp formation cargo", "cargo selection coat assembly", "selection coat assembly and", "assembly and stabilization membrane", "and stabilization membrane scission", "stabilization membrane scission and", "membrane scission and vesicle uncoating.", "and vesicle uncoating. although", "vesicle uncoating. although for", "uncoating. although for simplicity", "although for simplicity in this", "for simplicity in this pathway", "in this pathway the", "this pathway the steps", "pathway the steps leading", "the steps leading to a", "steps leading to a mature", "leading to a mature ccp", "to a mature ccp are", "a mature ccp are represented", "mature ccp are represented in", "ccp are represented in a", "are represented in a linear", "represented in a linear and", "in a linear and temporally", "a linear and temporally distinct", "linear and temporally distinct fashion", "temporally distinct fashion the", "distinct fashion the formation", "fashion the formation of", "the formation of a clathrin", "formation of a clathrin coated", "of a clathrin coated vesicle", "a clathrin coated vesicle is", "clathrin coated vesicle is a", "coated vesicle is a highly", "vesicle is a highly heterogeneous", "is a highly heterogeneous process", "a highly heterogeneous process and", "highly heterogeneous process and clear", "heterogeneous process and clear temporal", "process and clear temporal boundaries", "and clear temporal boundaries between", "clear temporal boundaries between these", "temporal boundaries between these processes", "boundaries between these processes may", "between these processes may not", "these processes may not exist", "may not exist see", "not exist see for", "exist see for instance", "see for instance taylor et", "for instance taylor et al", "taylor et al 2011", "al 2011 antonescu", "2011 antonescu et al", "antonescu et al 2011", "al 2011 reviewed", "2011 reviewed in kirchhausen", "reviewed in kirchhausen et al", "al 2014 . cargo", "2014 . cargo selection in", ". cargo selection in particular", "cargo selection in particular is", "selection in particular is a", "in particular is a critical", "particular is a critical aspect", "is a critical aspect of", "a critical aspect of the", "critical aspect of the formation", "aspect of the formation of", "of the formation of a", "the formation of a mature", "formation of a mature and", "of a mature and stable", "a mature and stable ccp", "and stable ccp and", "stable ccp and many", "ccp and many of", "and many of the proteins", "many of the proteins involved", "of the proteins involved in", "the proteins involved in the", "proteins involved in the initiation", "involved in the initiation and", "in the initiation and maturation", "the initiation and maturation of", "initiation and maturation of a", "and maturation of a ccp", "maturation of a ccp contribute", "of a ccp contribute to", "a ccp contribute to cargo", "ccp contribute to cargo selection", "contribute to cargo selection and", "to cargo selection and are", "cargo selection and are themselves", "selection and are themselves stabilized", "and are themselves stabilized upon", "are themselves stabilized upon incorporation", "themselves stabilized upon incorporation of", "stabilized upon incorporation of cargo", "upon incorporation of cargo into", "incorporation of cargo into the", "of cargo into the nascent", "cargo into the nascent vesicle", "the nascent vesicle reviewed", "nascent vesicle reviewed in", "vesicle reviewed in kirchhausen", "al 2014 mcmahon", "2014 mcmahon and boucrot", "and boucrot 2011 .



although", "boucrot 2011 .



although the", "2011 .



although the clathrin triskelion", ".



although the clathrin triskelion was", "the clathrin triskelion was identified", "clathrin triskelion was identified early", "triskelion was identified early as", "was identified early as a", "identified early as a major", "early as a major component", "as a major component of", "a major component of the", "major component of the coated", "component of the coated vesicles", "the coated vesicles clathrin", "coated vesicles clathrin does", "vesicles clathrin does not", "clathrin does not bind directly", "does not bind directly to", "not bind directly to membranes", "bind directly to membranes or", "directly to membranes or to", "to membranes or to the", "membranes or to the endocytosed", "or to the endocytosed cargo.", "the endocytosed cargo. vesicle", "endocytosed cargo. vesicle formation", "cargo. vesicle formation instead", "vesicle formation instead relies on", "formation instead relies on many", "instead relies on many proteins", "relies on many proteins and", "on many proteins and adaptors", "many proteins and adaptors that", "proteins and adaptors that can", "and adaptors that can bind", "adaptors that can bind the", "that can bind the plasma", "can bind the plasma membrane", "bind the plasma membrane and", "the plasma membrane and interact", "plasma membrane and interact with", "membrane and interact with cargo", "and interact with cargo molecules.", "interact with cargo molecules. cargo", "with cargo molecules. cargo selection", "cargo molecules. cargo selection depends", "molecules. cargo selection depends on", "cargo selection depends on the", "selection depends on the recognition", "depends on the recognition of", "on the recognition of endocytic", "the recognition of endocytic signals", "recognition of endocytic signals in", "of endocytic signals in cytoplasmic", "endocytic signals in cytoplasmic tails", "signals in cytoplasmic tails of", "in cytoplasmic tails of the", "cytoplasmic tails of the cargo", "tails of the cargo proteins", "of the cargo proteins by", "the cargo proteins by adaptors", "cargo proteins by adaptors that", "proteins by adaptors that interact", "by adaptors that interact with", "adaptors that interact with components", "that interact with components of", "interact with components of the", "with components of the vesicle's", "components of the vesicle's inner", "of the vesicle's inner coat.", "vesicle's inner coat. the", "inner coat. the classic", "coat. the classic adaptor", "the classic adaptor for clathrin", "classic adaptor for clathrin coated", "adaptor for clathrin coated vesicles", "for clathrin coated vesicles is", "clathrin coated vesicles is the", "coated vesicles is the tetrameric", "vesicles is the tetrameric ap", "is the tetrameric ap 2", "the tetrameric ap 2 complex", "ap 2 complex which", "2 complex which along", "complex which along with", "which along with clathrin was", "along with clathrin was identified", "with clathrin was identified early", "clathrin was identified early as", "major component of the coat.", "of the coat. some", "the coat. some cargo", "coat. some cargo indeed", "some cargo indeed bind directly", "cargo indeed bind directly to", "indeed bind directly to ap", "bind directly to ap 2", "to ap 2 but", "ap 2 but subsequent", "2 but subsequent work", "but subsequent work has revealed", "subsequent work has revealed a", "work has revealed a large", "has revealed a large family", "revealed a large family of", "a large family of proteins", "large family of proteins collectively", "family of proteins collectively known", "of proteins collectively known as", "proteins collectively known as clasps", "known as clasps clathrin", "clasps clathrin associated", "clathrin associated sorting proteins", "associated sorting proteins that", "sorting proteins that mediate", "proteins that mediate the", "that mediate the recruitment of", "mediate the recruitment of diverse", "the recruitment of diverse cargo", "recruitment of diverse cargo into", "of diverse cargo into the", "diverse cargo into the emerging", "cargo into the emerging clathrin", "into the emerging clathrin coated", "the emerging clathrin coated vesicles", "clathrin coated vesicles reviewed", "coated vesicles reviewed in", "vesicles reviewed in traub", "reviewed in traub and bonifacino", "traub and bonifacino 2013", "and bonifacino 2013 .", "2013 . many of", ". many of these", "many of these clasp proteins", "of these clasp proteins themselves", "these clasp proteins themselves interact", "clasp proteins themselves interact with", "proteins themselves interact with ap", "themselves interact with ap 2", "interact with ap 2 and", "with ap 2 and clathrin", "2 and clathrin coordinating", "and clathrin coordinating cargo", "clathrin coordinating cargo recruitment", "coordinating cargo recruitment with coat", "cargo recruitment with coat formation", "with coat formation schmid", "coat formation schmid et", "formation schmid et al", "schmid et al 2006", "al 2006 edeling", "2006 edeling et al", "edeling et al 2006", "al 2006 reviewed", "2006 reviewed in traub", "bonifacino 2013 kirchhausen", "2013 kirchhausen et al", "2014 .


initiation of", ".


initiation of ccp", "


initiation of ccp formation is", "of ccp formation is also", "ccp formation is also influenced", "formation is also influenced by", "is also influenced by lipid", "also influenced by lipid composition", "by lipid composition regulated", "lipid composition regulated by", "composition regulated by clathrin", "regulated by clathrin associated phosphatases", "by clathrin associated phosphatases and", "clathrin associated phosphatases and kinases", "phosphatases and kinases reviewed", "and kinases reviewed in", "kinases reviewed in picas", "reviewed in picas et al", "picas et al 2016", "al 2016 . the", "2016 . the plasma membrane", ". the plasma membrane is", "the plasma membrane is enriched", "plasma membrane is enriched in", "membrane is enriched in pi", "is enriched in pi 4", "enriched in pi 4 5", "in pi 4 5 p2.", "4 5 p2. many", "5 p2. many of", "p2. many of the", "the proteins involved in initiating", "proteins involved in initiating clathrin", "involved in initiating clathrin coated", "in initiating clathrin coated pit", "initiating clathrin coated pit formation", "clathrin coated pit formation bind", "coated pit formation bind to", "pit formation bind to pi", "formation bind to pi 4", "bind to pi 4 5", "to pi 4 5 p2", "pi 4 5 p2 and", "4 5 p2 and induce", "5 p2 and induce membrane", "p2 and induce membrane curvature", "and induce membrane curvature through", "induce membrane curvature through their", "membrane curvature through their bar", "curvature through their bar domains", "their bar domains reviewed", "bar domains reviewed in", "domains reviewed in mcmahon", "reviewed in mcmahon and boucrot", "boucrot 2011 daumke", "2011 daumke et al", "daumke et al 2014", "2014 . epsin also", ". epsin also contributes", "epsin also contributes to early", "also contributes to early membrane", "contributes to early membrane curvature", "to early membrane curvature through", "early membrane curvature through its", "membrane curvature through its epsin", "curvature through its epsin n", "through its epsin n terminal", "its epsin n terminal homology", "n terminal homology enth", "homology enth domain", "enth domain which", "domain which promotes membrane", "which promotes membrane curvature by", "promotes membrane curvature by inserting", "membrane curvature by inserting into", "curvature by inserting into the", "by inserting into the lipid", "inserting into the lipid bilayer", "the lipid bilayer ford", "lipid bilayer ford et", "bilayer ford et al", "ford et al 2002", "et al 2002 .", "al 2002 .

following", ".

following initiation some", "

following initiation some ccps", "initiation some ccps progress", "some ccps progress to formation", "ccps progress to formation of", "progress to formation of vesicles", "formation of vesicles while", "of vesicles while others", "vesicles while others undergo", "while others undergo disassembly at", "others undergo disassembly at the", "undergo disassembly at the cell", "disassembly at the cell surface", "at the cell surface without", "the cell surface without producing", "cell surface without producing vesicles", "without producing vesicles ehrlich", "producing vesicles ehrlich et", "vesicles ehrlich et al", "ehrlich et al 2004", "al 2004 loerke", "2004 loerke et al", "loerke et al 2009", "al 2009 loerke", "2009 loerke et al", "loerke et al 2011", "al 2011 aguet", "2011 aguet et al", "aguet et al 2013", "al 2013 taylor", "2013 taylor et al", "et al 2011 .", "al 2011 . the", "2011 . the assembly and", ". the assembly and stabilization", "the assembly and stabilization of", "assembly and stabilization of nascent", "and stabilization of nascent ccps", "stabilization of nascent ccps is", "of nascent ccps is regulated", "nascent ccps is regulated by", "ccps is regulated by several", "is regulated by several proteins", "regulated by several proteins and", "by several proteins and lipids", "proteins and lipids mettlen", "and lipids mettlen et", "lipids mettlen et al", "mettlen et al 2009", "al 2009 antonescu", "2009 antonescu et al", "et al 2011 .


maturation", "al 2011 .


maturation of", "2011 .


maturation of the emerging", ".


maturation of the emerging clathrin", "of the emerging clathrin coated", "the emerging clathrin coated vesicle", "emerging clathrin coated vesicle is", "clathrin coated vesicle is accompanied", "coated vesicle is accompanied by", "vesicle is accompanied by further", "is accompanied by further changes", "accompanied by further changes in", "by further changes in the", "further changes in the lipid", "changes in the lipid composition", "in the lipid composition of", "the lipid composition of the", "lipid composition of the membrane", "composition of the membrane and", "of the membrane and increased", "the membrane and increased membrane", "membrane and increased membrane curvature", "increased membrane curvature promoted", "membrane curvature promoted by", "curvature promoted by the", "promoted by the recruitment of", "by the recruitment of n", "the recruitment of n bar", "recruitment of n bar domain", "of n bar domain containing", "n bar domain containing proteins", "domain containing proteins reviewed", "containing proteins reviewed in", "proteins reviewed in daumke", "reviewed in daumke et al", "al 2014 ferguson", "2014 ferguson and de", "and de camilli 2012", "camilli 2012 picas", "2012 picas et al", "al 2016 . some", "2016 . some n bar", ". some n bar domain", "some n bar domain containing", "bar domain containing proteins also", "domain containing proteins also contribute", "containing proteins also contribute to", "proteins also contribute to the", "also contribute to the recruitment", "contribute to the recruitment of", "to the recruitment of the", "the recruitment of the large", "recruitment of the large gtpase", "of the large gtpase dynamin", "large gtpase dynamin which", "gtpase dynamin which is", "dynamin which is responsible", "which is responsible for scission", "is responsible for scission of", "responsible for scission of the", "for scission of the mature", "scission of the mature vesicle", "of the mature vesicle from", "the mature vesicle from the", "mature vesicle from the plasma", "vesicle from the plasma membrane", "the plasma membrane koh", "plasma membrane koh et", "membrane koh et al", "koh et al 2007", "al 2007 lundmark", "2007 lundmark and carlsson", "lundmark and carlsson 2003", "carlsson 2003 soulet", "2003 soulet et al", "soulet et al 2005", "al 2005 david", "2005 david et al", "david et al 1996", "al 1996 owen", "1996 owen et al", "owen et al 1998", "al 1998 shupliakov", "1998 shupliakov et al", "shupliakov et al 1997", "al 1997 taylor", "1997 taylor et al", "al 2011 ferguson", "2011 ferguson et al", "ferguson et al 2009", "al 2009 aguet", "2009 aguet et al", "al 2013 posor", "2013 posor et al", "posor et al 2013", "al 2013 chappie", "2013 chappie et al", "chappie et al 2010", "al 2010 shnyrova", "2010 shnyrova et al", "shnyrova et al 2013", "al 2013 reviewed", "2013 reviewed in mettlen", "reviewed in mettlen et al", "al 2009 daumke", "2009 daumke et al", "2014 . after vesicle", ". after vesicle scission", "after vesicle scission the", "vesicle scission the clathrin", "scission the clathrin coat", "the clathrin coat is dissociated", "clathrin coat is dissociated from", "coat is dissociated from the", "is dissociated from the new", "dissociated from the new vesicle", "from the new vesicle by", "the new vesicle by the", "new vesicle by the atpase", "vesicle by the atpase hspa8", "the atpase hspa8 also", "atpase hspa8 also known", "hspa8 also known as", "known as hsc70 and", "as hsc70 and its", "hsc70 and its dnaj", "and its dnaj cofactor auxilin", "dnaj cofactor auxilin priming", "cofactor auxilin priming the", "auxilin priming the vesicle", "priming the vesicle for fusion", "the vesicle for fusion with", "vesicle for fusion with a", "for fusion with a subsequent", "fusion with a subsequent endocytic", "with a subsequent endocytic compartment", "a subsequent endocytic compartment and", "subsequent endocytic compartment and releasing", "endocytic compartment and releasing clathrin", "compartment and releasing clathrin for", "and releasing clathrin for reuse", "for reuse reviewed", "reuse reviewed in", "boucrot 2011 sousa", "2011 sousa and laufer", "sousa and laufer 2015", "and laufer 2015 ." ] }, { "record_id": "GLY_000594_1_619", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8863795", "r hsa", "hsa 8863795", "r hsa 8863795" ] }, { "record_id": "GLY_000594_1_619", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "downregulation of", "of erbb2", "erbb2 signaling", "downregulation of erbb2", "of erbb2 signaling", "downregulation of erbb2 signaling", "signaling by", "by erbb2", "erbb2 can", "can be", "be downregulated", "downregulated by", "by ubiquitination", "ubiquitination and", "and subsequent", "subsequent proteasome", "proteasome dependent", "dependent degradation", "degradation of", "erbb2 or", "or activated", "activated erbb2", "erbb2 heterodimers.", "heterodimers. in", "in addition", "protein tyrosine", "tyrosine phosphatases", "phosphatases that", "that dephosphorylate", "dephosphorylate tyrosine", "tyrosine residues", "residues in", "in the", "the c", "c terminus", "terminus of", "erbb2 prevent", "prevent the", "the recruitment", "recruitment of", "of adapter", "adapter proteins", "proteins involved", "involved in", "in signal", "signal transduction", "thus attenuating", "attenuating erbb2", "erbb2 signaling.
stub1", "and cul5", "cul5 are", "are e3", "e3 ubiquitin", "ubiquitin ligases", "ligases that", "that can", "can target", "target non", "non activated", "erbb2 for", "for proteasome", "xu et", "et al.", "al. 2002", "ehrlich et", "al. 2009", "2009 .", ". rnf41", "is an", "an e3", "ubiquitin ligase", "ligase that", "that targets", "targets erbb3", "erbb3 and", "and activated", "activated heterodimers", "heterodimers of", "erbb2 and", "and erbb3", "erbb3 for", "degradation by", "by ubiquitinating", "ubiquitinating erbb3", "cao et", "al. 2007", "2007 .
two", ".
two protein", "phosphatases of", "of the", "the pest", "pest family", "ptpn12 and", "and ptpn18", "thus preventing", "preventing signal", "transduction to", "to ras", "ras and", "and pi3k", "pi3k effectors", "sun et", "al. 2011", "wang et", "al. 2014", "2014 .", "signaling by erbb2", "by erbb2 can", "erbb2 can be", "can be downregulated", "be downregulated by", "downregulated by ubiquitination", "by ubiquitination and", "ubiquitination and subsequent", "and subsequent proteasome", "subsequent proteasome dependent", "proteasome dependent degradation", "dependent degradation of", "degradation of erbb2", "of erbb2 or", "erbb2 or activated", "or activated erbb2", "activated erbb2 heterodimers.", "erbb2 heterodimers. in", "heterodimers. in addition", "addition protein", "protein tyrosine phosphatases", "tyrosine phosphatases that", "phosphatases that dephosphorylate", "that dephosphorylate tyrosine", "dephosphorylate tyrosine residues", "tyrosine residues in", "residues in the", "in the c", "the c terminus", "c terminus of", "terminus of erbb2", "of erbb2 prevent", "erbb2 prevent the", "prevent the recruitment", "the recruitment of", "recruitment of adapter", "of adapter proteins", "adapter proteins involved", "proteins involved in", "involved in signal", "in signal transduction", "transduction thus", "thus attenuating erbb2", "attenuating erbb2 signaling.
stub1", "signaling.
stub1 chip", "chip and", "and cul5 are", "cul5 are e3", "are e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases that", "ligases that can", "that can target", "can target non", "target non activated", "non activated erbb2", "activated erbb2 for", "erbb2 for proteasome", "for proteasome dependent", "degradation xu", "xu et al.", "et al. 2002", "2002 ehrlich", "ehrlich et al.", "et al. 2009", "al. 2009 .", "2009 . rnf41", "rnf41 nrdp1", "nrdp1 is", "is an e3", "an e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase that", "ligase that targets", "that targets erbb3", "targets erbb3 and", "erbb3 and activated", "and activated heterodimers", "activated heterodimers of", "heterodimers of erbb2", "of erbb2 and", "erbb2 and erbb3", "and erbb3 for", "erbb3 for proteasome", "dependent degradation by", "degradation by ubiquitinating", "by ubiquitinating erbb3", "erbb3 cao", "cao et al.", "et al. 2007", "al. 2007 .
two", "2007 .
two protein", ".
two protein tyrosine", "tyrosine phosphatases of", "phosphatases of the", "of the pest", "the pest family", "family ptpn12", "ptpn12 and ptpn18", "ptpn18 dephosphorylate", "erbb2 thus", "thus preventing signal", "preventing signal transduction", "signal transduction to", "transduction to ras", "to ras and", "ras and pi3k", "and pi3k effectors", "effectors sun", "sun et al.", "et al. 2011", "2011 wang", "wang et al.", "et al. 2014", "al. 2014 .", "signaling by erbb2 can", "by erbb2 can be", "erbb2 can be downregulated", "can be downregulated by", "be downregulated by ubiquitination", "downregulated by ubiquitination and", "by ubiquitination and subsequent", "ubiquitination and subsequent proteasome", "and subsequent proteasome dependent", "subsequent proteasome dependent degradation", "proteasome dependent degradation of", "dependent degradation of erbb2", "degradation of erbb2 or", "of erbb2 or activated", "erbb2 or activated erbb2", "or activated erbb2 heterodimers.", "activated erbb2 heterodimers. in", "erbb2 heterodimers. in addition", "in addition protein", "addition protein tyrosine", "protein tyrosine phosphatases that", "tyrosine phosphatases that dephosphorylate", "phosphatases that dephosphorylate tyrosine", "that dephosphorylate tyrosine residues", "dephosphorylate tyrosine residues in", "tyrosine residues in the", "residues in the c", "in the c terminus", "the c terminus of", "c terminus of erbb2", "terminus of erbb2 prevent", "of erbb2 prevent the", "erbb2 prevent the recruitment", "prevent the recruitment of", "the recruitment of adapter", "recruitment of adapter proteins", "of adapter proteins involved", "adapter proteins involved in", "proteins involved in signal", "involved in signal transduction", "signal transduction thus", "transduction thus attenuating", "thus attenuating erbb2 signaling.
stub1", "erbb2 signaling.
stub1 chip", "chip and cul5", "and cul5 are e3", "cul5 are e3 ubiquitin", "are e3 ubiquitin ligases", "e3 ubiquitin ligases that", "ubiquitin ligases that can", "ligases that can target", "that can target non", "can target non activated", "target non activated erbb2", "non activated erbb2 for", "activated erbb2 for proteasome", "erbb2 for proteasome dependent", "for proteasome dependent degradation", "dependent degradation xu", "degradation xu et", "xu et al. 2002", "al. 2002 ehrlich", "2002 ehrlich et", "ehrlich et al. 2009", "et al. 2009 .", "al. 2009 . rnf41", ". rnf41 nrdp1", "nrdp1 is an", "is an e3 ubiquitin", "an e3 ubiquitin ligase", "e3 ubiquitin ligase that", "ubiquitin ligase that targets", "ligase that targets erbb3", "that targets erbb3 and", "targets erbb3 and activated", "erbb3 and activated heterodimers", "and activated heterodimers of", "activated heterodimers of erbb2", "heterodimers of erbb2 and", "of erbb2 and erbb3", "erbb2 and erbb3 for", "and erbb3 for proteasome", "erbb3 for proteasome dependent", "proteasome dependent degradation by", "dependent degradation by ubiquitinating", "degradation by ubiquitinating erbb3", "ubiquitinating erbb3 cao", "erbb3 cao et", "cao et al. 2007", "et al. 2007 .
two", "al. 2007 .
two protein", "2007 .
two protein tyrosine", ".
two protein tyrosine phosphatases", "protein tyrosine phosphatases of", "tyrosine phosphatases of the", "phosphatases of the pest", "of the pest family", "pest family ptpn12", "family ptpn12 and", "and ptpn18 dephosphorylate", "ptpn18 dephosphorylate tyrosine", "of erbb2 thus", "erbb2 thus preventing", "thus preventing signal transduction", "preventing signal transduction to", "signal transduction to ras", "transduction to ras and", "to ras and pi3k", "ras and pi3k effectors", "pi3k effectors sun", "effectors sun et", "sun et al. 2011", "al. 2011 wang", "2011 wang et", "wang et al. 2014", "et al. 2014 .", "signaling by erbb2 can be", "by erbb2 can be downregulated", "erbb2 can be downregulated by", "can be downregulated by ubiquitination", "be downregulated by ubiquitination and", "downregulated by ubiquitination and subsequent", "by ubiquitination and subsequent proteasome", "ubiquitination and subsequent proteasome dependent", "and subsequent proteasome dependent degradation", "subsequent proteasome dependent degradation of", "proteasome dependent degradation of erbb2", "dependent degradation of erbb2 or", "degradation of erbb2 or activated", "of erbb2 or activated erbb2", "erbb2 or activated erbb2 heterodimers.", "or activated erbb2 heterodimers. in", "activated erbb2 heterodimers. in addition", "heterodimers. in addition protein", "in addition protein tyrosine", "addition protein tyrosine phosphatases", "protein tyrosine phosphatases that dephosphorylate", "tyrosine phosphatases that dephosphorylate tyrosine", "phosphatases that dephosphorylate tyrosine residues", "that dephosphorylate tyrosine residues in", "dephosphorylate tyrosine residues in the", "tyrosine residues in the c", "residues in the c terminus", "in the c terminus of", "the c terminus of erbb2", "c terminus of erbb2 prevent", "terminus of erbb2 prevent the", "of erbb2 prevent the recruitment", "erbb2 prevent the recruitment of", "prevent the recruitment of adapter", "the recruitment of adapter proteins", "recruitment of adapter proteins involved", "of adapter proteins involved in", "adapter proteins involved in signal", "proteins involved in signal transduction", "in signal transduction thus", "signal transduction thus attenuating", "transduction thus attenuating erbb2", "attenuating erbb2 signaling.
stub1 chip", "signaling.
stub1 chip and", "chip and cul5 are", "and cul5 are e3 ubiquitin", "cul5 are e3 ubiquitin ligases", "are e3 ubiquitin ligases that", "e3 ubiquitin ligases that can", "ubiquitin ligases that can target", "ligases that can target non", "that can target non activated", "can target non activated erbb2", "target non activated erbb2 for", "non activated erbb2 for proteasome", "activated erbb2 for proteasome dependent", "erbb2 for proteasome dependent degradation", "proteasome dependent degradation xu", "dependent degradation xu et", "degradation xu et al.", "et al. 2002 ehrlich", "al. 2002 ehrlich et", "2002 ehrlich et al.", "ehrlich et al. 2009 .", "et al. 2009 . rnf41", "2009 . rnf41 nrdp1", "rnf41 nrdp1 is", "nrdp1 is an e3", "is an e3 ubiquitin ligase", "an e3 ubiquitin ligase that", "e3 ubiquitin ligase that targets", "ubiquitin ligase that targets erbb3", "ligase that targets erbb3 and", "that targets erbb3 and activated", "targets erbb3 and activated heterodimers", "erbb3 and activated heterodimers of", "and activated heterodimers of erbb2", "activated heterodimers of erbb2 and", "heterodimers of erbb2 and erbb3", "of erbb2 and erbb3 for", "erbb2 and erbb3 for proteasome", "and erbb3 for proteasome dependent", "erbb3 for proteasome dependent degradation", "for proteasome dependent degradation by", "proteasome dependent degradation by ubiquitinating", "dependent degradation by ubiquitinating erbb3", "by ubiquitinating erbb3 cao", "ubiquitinating erbb3 cao et", "erbb3 cao et al.", "cao et al. 2007 .
two", "et al. 2007 .
two protein", "al. 2007 .
two protein tyrosine", "2007 .
two protein tyrosine phosphatases", ".
two protein tyrosine phosphatases of", "protein tyrosine phosphatases of the", "tyrosine phosphatases of the pest", "phosphatases of the pest family", "the pest family ptpn12", "pest family ptpn12 and", "family ptpn12 and ptpn18", "ptpn12 and ptpn18 dephosphorylate", "and ptpn18 dephosphorylate tyrosine", "ptpn18 dephosphorylate tyrosine residues", "terminus of erbb2 thus", "of erbb2 thus preventing", "erbb2 thus preventing signal", "thus preventing signal transduction to", "preventing signal transduction to ras", "signal transduction to ras and", "transduction to ras and pi3k", "to ras and pi3k effectors", "and pi3k effectors sun", "pi3k effectors sun et", "effectors sun et al.", "et al. 2011 wang", "al. 2011 wang et", "2011 wang et al.", "wang et al. 2014 ." ] }, { "record_id": "GLY_000594_1_620", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8866652", "r hsa", "hsa 8866652", "r hsa 8866652" ] }, { "record_id": 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et al.", "in deshaies et al. 2009", "et al. 2009 metzger", "al. 2009 metzger et", "2009 metzger et al.", "et al. 2012 metzger", "al. 2012 metzger et", "2012 metzger et al.", "al. 2014 hect", "2014 hect type", "hect type ligases reviewed", "ligases reviewed in rotin", "reviewed in rotin et al.", "in rotin et al. 2009", "al. 2012 and", "2012 and rbr", "rbr type ligases reviewed", "ligases reviewed in dove", "reviewed in dove et al.", "in dove et al. 2016", "dove et al. 2016 .", "et al. 2016 . a", "al. 2016 . a subset", "2016 . a subset of", ". a subset of the", "a subset of the ring", "subset of the ring type", "of the ring type ligases", "the ring type ligases participate", "ring type ligases participate in", "type ligases participate in cullin", "ligases participate in cullin ring", "participate in cullin ring ligase", "in cullin ring ligase complexes", "ring ligase complexes crls", "ligase complexes crls which", "complexes crls which include", "crls which include scf complexes", 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some", "et al. 2014 .
some e3", "al. 2014 .
some e3 e2", "2014 .
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"GLY_000594_1_623", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rab geranylgeranylation", "human cells", "cells have", "have more", "more than", "than 60", "60 rab", "rab proteins", "proteins that", "that are", "are involved", "involved in", "in trafficking", "trafficking of", "of proteins", "proteins in", "in the", "the endolysosomal", "endolysosomal system.", "system. these", "these small", "small gtpases", "gtpases contribute", "contribute to", "to trafficking", "trafficking specificity", "specificity by", "by localizing", "localizing to", "to the", "the membranes", "membranes of", "of different", "different endocytic", "endocytic compartments", "compartments and", "and interacting", "interacting with", "with effectors", "effectors such", "such as", "as sorting", "sorting adaptors", "tethering factors", "phosphatases and", "and tubular", "tubular vesicular", "vesicular cargo", "reviewed in", "in stenmark", "stenmark et", "et al", "wandinger ness", "ness and", "and zerial", "2014 .", ". rab", "rab localization", "localization depends", "depends on", "on a", "a number", "number of", "of factors", "factors including", "including c", "c terminal", "terminal prenylation", "the sequence", "sequence of", "of an", "an upstream", "upstream hypervariable", "hypervariable regions", "regions and", "and what", "what nucleotide", "nucleotide is", "is bound", "chavrier et", "ullrich et", "soldati et", "farnsworth et", "wu et", ". in", "the active", "gtp bound", "bound form", "prenylated rab", "proteins are", "are membrane", "membrane associated", "while in", "the inactive", "inactive gdp", "gdp bound", "rabs are", "are extracted", "extracted from", "from the", "the target", "target membrane", "membrane and", "and exist", "exist in", "in a", "a soluble", "soluble form", "form in", "in complex", "complex with", "with gdp", "gdp dissociation", "dissociation inhibitors", "gavriljuk et", "2103 .", ". conversion", "conversion between", "between the", "inactive and", "and active", "active form", "form relies", "relies on", "on the", "the activities", "activities of", "of rab", "rab guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "and gtpase", "gtpase activating", "activating proteins", "yoshimura et", "pan et", "frasa et", "2014 .
newly", ".
newly synthesized", "synthesized rabs", "are bound", "bound by", "by a", "a rab", "rab escort", "escort protein", "also known", "known as", "as rep1", "or chml", "alexandrov et", "shen and", "and seabra", "1996 .", ". chm/rep", "chm/rep proteins", "are the", "the substrate", "substrate binding", "binding component", "component of", "of the", "the trimeric", "trimeric rab", "rab geranylgeranyltransferase", "geranylgeranyltransferase enzyme", "along with", "with the", "the two", "two catalytic", "catalytic subunits", "subunits rabggta", "rabggta and", "and rabggtb", "gutkowska and", "and swiezewska", "palsuledesai and", "and distefano", "2015 .", ". rep", "rep proteins", "proteins recruit", "recruit the", "the unmodified", "unmodified rab", "rab in", "in its", "its gdp", "bound state", "state to", "the ggtase", "ggtase for", "for sequential", "sequential geranylgeranylation", "geranylgeranylation at", "at one", "one or", "or two", "two c", "terminal cysteine", "cysteine residues", "seabra et", "al 1996", "baron and", "2008 .", ". after", "after geranylgeranylation", "proteins remain", "remain in", "the geranylgeranylated", "geranylgeranylated rab", "rab and", "and escort", "escort it", "it to", "to its", "its target", "where its", "its activity", "activity is", "is regulated", "regulated by", "by gaps", "gdis and", "and membrane", "membrane bound", "bound gdi", "gdi displacement", "displacement factors", "sivars et", "human cells have", "cells have more", "have more than", "more than 60", "than 60 rab", "60 rab proteins", "rab proteins that", "proteins that are", "that are involved", "are involved in", "involved in trafficking", "in trafficking of", "trafficking of proteins", "of proteins in", "proteins in the", "in the endolysosomal", "the endolysosomal system.", "endolysosomal system. these", "system. these small", "these small gtpases", "small gtpases contribute", "gtpases contribute to", "contribute to trafficking", "to trafficking specificity", "trafficking specificity by", "specificity by localizing", "by localizing to", "localizing to the", "to the membranes", "the membranes of", "membranes of different", "of different endocytic", "different endocytic compartments", "endocytic compartments and", "compartments and interacting", "and interacting with", "interacting with effectors", "with effectors such", "effectors such as", "such as sorting", "as sorting adaptors", "adaptors tethering", "factors kinases", "kinases phosphatases", "phosphatases and tubular", "and tubular vesicular", "tubular vesicular cargo", "cargo reviewed", "reviewed in stenmark", "in stenmark et", "stenmark et al", "al 2009", "2009 wandinger", "wandinger ness and", "ness and zerial", "zerial 2014", "2014 . rab", ". rab localization", "rab localization depends", "localization depends on", "depends on a", "on a number", "a number of", "number of factors", "of factors including", "factors including c", "including c terminal", "c terminal prenylation", "prenylation the", "the sequence of", "sequence of an", "of an upstream", "an upstream hypervariable", "upstream hypervariable regions", "hypervariable regions and", "regions and what", "and what nucleotide", "what nucleotide is", "nucleotide is bound", "bound chavrier", "chavrier et al", "al 1991", "1991 ullrich", "ullrich et al", "al 1993", "1993 soldati", "soldati et al", "al 1994", "1994 farnsworth", "farnsworth et al", "1994 seabra", "seabra 1996", "1996 wu", "wu et al", "al 2010", "2010 reviewed", "stenmark 2009", "2014 . in", ". in the", "in the active", "active gtp", "gtp bound form", "form prenylated", "prenylated rab proteins", "rab proteins are", "proteins are membrane", "are membrane associated", "associated while", "while in the", "in the inactive", "the inactive gdp", "inactive gdp bound", "gdp bound form", "form rabs", "rabs are extracted", "are extracted from", "extracted from the", "from the target", "the target membrane", "target membrane and", "membrane and exist", "and exist in", "exist in a", "in a soluble", "a soluble form", "soluble form in", "form in complex", "in complex with", "complex with gdp", "with gdp dissociation", "gdp dissociation inhibitors", "inhibitors gdis", "1994 gavriljuk", "gavriljuk et al", "al 2103", "2103 . conversion", ". conversion between", "conversion between the", "between the inactive", "the inactive and", "inactive and active", "and active form", "active form relies", "form relies on", "relies on the", "on the activities", "the activities of", "activities of rab", "of rab guanine", "rab guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factors", "factors gefs", "gefs and", "and gtpase activating", "gtpase activating proteins", "proteins gaps", "yoshimura et al", "2010 wu", "al 2011", "2011 pan", "pan et al", "al 2006", "2006 frasa", "frasa et al", "al 2012", "2012 reviewed", "2014 .
newly synthesized", ".
newly synthesized rabs", "synthesized rabs are", "rabs are bound", "are bound by", "bound by a", "by a rab", "a rab escort", "rab escort protein", "protein chm", "chm also", "also known as", "known as rep1", "rep1 or", "chml rep2", "alexandrov et al", "1994 shen", "shen and seabra", "1996 . chm/rep", ". chm/rep proteins", "chm/rep proteins are", "proteins are the", "are the substrate", "the substrate binding", "substrate binding component", "binding component of", "component of the", "of the trimeric", "the trimeric rab", "trimeric rab geranylgeranyltransferase", "rab geranylgeranyltransferase enzyme", "enzyme ggtaseii", "ggtaseii along", "along with the", "with the two", "the two catalytic", "two catalytic subunits", "catalytic subunits rabggta", "subunits rabggta and", "rabggta and rabggtb", "rabggtb reviewed", "in gutkowska", "gutkowska and swiezewska", "swiezewska 2012", "2012 palsuledesai", "palsuledesai and distefano", "distefano 2015", "2015 . rep", ". rep proteins", "rep proteins recruit", "proteins recruit the", "recruit the unmodified", "the unmodified rab", "unmodified rab in", "rab in its", "in its gdp", "its gdp bound", "gdp bound state", "bound state to", "state to the", "to the ggtase", "the ggtase for", "ggtase for sequential", "for sequential geranylgeranylation", "sequential geranylgeranylation at", "geranylgeranylation at one", "at one or", "one or two", "or two c", "two c terminal", "c terminal cysteine", "terminal cysteine residues", "residues alexandrov", "seabra et al", "et al 1996", "1996 shen", "1996 baron", "baron and seabra", "seabra 2008", "2008 . after", ". after geranylgeranylation", "geranylgeranylation chm/rep", "chm/rep proteins remain", "proteins remain in", "remain in complex", "complex with the", "with the geranylgeranylated", "the geranylgeranylated rab", "geranylgeranylated rab and", "rab and escort", "and escort it", "escort it to", "it to its", "to its target", "its target membrane", "membrane where", "where its activity", "its activity is", "activity is regulated", "is regulated by", "regulated by gaps", "gaps gefs", "gefs gdis", "gdis and membrane", "and membrane bound", "membrane bound gdi", "bound gdi displacement", "gdi displacement factors", "factors gdfs", "sivars et al", "al 2003", "2003 reviewed", "human cells have more", "cells have more than", "have more than 60", "more than 60 rab", "than 60 rab proteins", "60 rab proteins that", "rab proteins that are", "proteins that are involved", "that are involved in", "are involved in trafficking", "involved in trafficking of", "in trafficking of proteins", "trafficking of proteins in", "of proteins in the", "proteins in the endolysosomal", "in the endolysosomal system.", "the endolysosomal system. these", "endolysosomal system. these small", "system. these small gtpases", "these small gtpases contribute", "small gtpases contribute to", "gtpases contribute to trafficking", "contribute to trafficking specificity", "to trafficking specificity by", "trafficking specificity by localizing", "specificity by localizing to", "by localizing to the", "localizing to the membranes", "to the membranes of", "the membranes of different", "membranes of different endocytic", "of different endocytic compartments", "different endocytic compartments and", "endocytic compartments and interacting", "compartments and interacting with", "and interacting with effectors", "interacting with effectors such", "with effectors such as", "effectors such as sorting", "such as sorting adaptors", "sorting adaptors tethering", "adaptors tethering factors", "tethering factors kinases", "kinases phosphatases and", "phosphatases and tubular vesicular", "and tubular vesicular cargo", "vesicular cargo reviewed", "cargo reviewed in", "reviewed in stenmark et", "in stenmark et al", "et al 2009", "2009 wandinger ness", "wandinger ness and zerial", "and zerial 2014", "zerial 2014 .", "2014 . rab localization", ". rab localization depends", "rab localization depends on", "localization depends on a", "depends on a number", "on a number of", "a number of factors", "number of factors including", "of factors including c", "factors including c terminal", "including c terminal prenylation", "terminal prenylation the", "prenylation the sequence", "the sequence of an", "sequence of an upstream", "of an upstream hypervariable", "an upstream hypervariable regions", "upstream hypervariable regions and", "hypervariable regions and what", "regions and what nucleotide", "and what nucleotide is", "what nucleotide is bound", "is bound chavrier", "bound chavrier et", "et al 1991", "1991 ullrich et", "et al 1993", "1993 soldati et", "et al 1994", "1994 farnsworth et", "1996 wu et", "et al 2010", "2010 reviewed in", "in stenmark 2009", "2014 . in the", ". in the active", "the active gtp", "active gtp bound", "bound form prenylated", "form prenylated rab", "prenylated rab proteins are", "rab proteins are membrane", "proteins are membrane associated", "membrane associated while", "associated while in", "while in the inactive", "in the inactive gdp", "the inactive gdp bound", "inactive gdp bound form", "bound form rabs", "form rabs are", "rabs are extracted from", "are extracted from the", "extracted from the target", "from the target membrane", "the target membrane and", "target membrane and exist", "membrane and exist in", "and exist in a", "exist in a soluble", "in a soluble form", "a soluble form in", "soluble form in complex", "form in complex with", "in complex with gdp", "complex with gdp dissociation", "with gdp dissociation inhibitors", "dissociation inhibitors gdis", "gdis ullrich", "1994 gavriljuk et", "et al 2103", "al 2103 .", "2103 . conversion between", ". conversion between the", "conversion between the inactive", "between the inactive and", "the inactive and active", "inactive and active form", "and active form relies", "active form relies on", "form relies on the", "relies on the activities", "on the activities of", "the activities of rab", "activities of rab guanine", "of rab guanine nucleotide", "rab guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs and gtpase", "and gtpase activating proteins", "activating proteins gaps", "gaps yoshimura", "2010 wu et", "et al 2011", "2011 pan et", "et al 2006", "2006 frasa et", "et al 2012", "2012 reviewed in", "zerial 2014 .
newly", "2014 .
newly synthesized rabs", ".
newly synthesized rabs are", "synthesized rabs are bound", "rabs are bound by", "are bound by a", "bound by a rab", "by a rab escort", "a rab escort protein", "escort protein chm", "chm also known", "also known as rep1", "as rep1 or", "rep1 or chml", "or chml rep2", "rep2 alexandrov", "1994 shen and", "and seabra 1996", "seabra 1996 .", "1996 . chm/rep proteins", ". chm/rep proteins are", "chm/rep proteins are the", "proteins are the substrate", "are the substrate binding", "the substrate binding component", "substrate binding component of", "binding component of the", "component of the trimeric", "of the trimeric rab", "the trimeric rab geranylgeranyltransferase", "trimeric rab geranylgeranyltransferase enzyme", "geranylgeranyltransferase enzyme ggtaseii", "ggtaseii along with", "along with the two", "with the two catalytic", "the two catalytic subunits", "two catalytic subunits rabggta", "catalytic subunits rabggta and", "subunits rabggta and rabggtb", "and rabggtb reviewed", "rabggtb reviewed in", "reviewed in gutkowska", "in gutkowska and", "and swiezewska 2012", "2012 palsuledesai and", "and distefano 2015", "distefano 2015 .", "2015 . rep proteins", ". rep proteins recruit", "rep proteins recruit the", "proteins recruit the unmodified", "recruit the unmodified rab", "the unmodified rab in", "unmodified rab in its", "rab in its gdp", "in its gdp bound", "its gdp bound state", "gdp bound state to", "bound state to the", "state to the ggtase", "to the ggtase for", "the ggtase for sequential", "ggtase for sequential geranylgeranylation", "for sequential geranylgeranylation at", "sequential geranylgeranylation at one", "geranylgeranylation at one or", "at one or two", "one or two c", "or two c terminal", "two c terminal cysteine", "c terminal cysteine residues", "cysteine residues alexandrov", "residues alexandrov et", "1994 seabra et", "seabra et al 1996", "al 1996 shen", "1996 shen and", "1996 baron and", "and seabra 2008", "seabra 2008 .", "2008 . after geranylgeranylation", "after geranylgeranylation chm/rep", "geranylgeranylation chm/rep proteins", "chm/rep proteins remain in", "proteins remain in complex", "remain in complex with", "in complex with the", "complex with the geranylgeranylated", "with the geranylgeranylated rab", "the geranylgeranylated rab and", "geranylgeranylated rab and escort", "rab and escort it", "and escort it to", "escort it to its", "it to its target", "to its target membrane", "target membrane where", "membrane where its", "where its activity is", "its activity is regulated", "activity is regulated by", "is regulated by gaps", "by gaps gefs", "gefs gdis and", "gdis and membrane bound", "and membrane bound gdi", "membrane bound gdi displacement", "bound gdi displacement factors", "displacement factors gdfs", "gdfs sivars", "et al 2003", "2003 reviewed in", "human cells have more than", "cells have more than 60", "have more than 60 rab", "more than 60 rab proteins", "than 60 rab proteins that", "60 rab proteins that are", "rab proteins that are involved", "proteins that are involved in", "that are involved in trafficking", "are involved in trafficking of", "involved in trafficking of proteins", "in trafficking of proteins in", "trafficking of proteins in the", "of proteins in the endolysosomal", "proteins in the endolysosomal system.", "in the endolysosomal system. these", "the endolysosomal system. these small", "endolysosomal system. these small gtpases", "system. these small gtpases contribute", "these small gtpases contribute to", "small gtpases contribute to trafficking", "gtpases contribute to trafficking specificity", "contribute to trafficking specificity by", "to trafficking specificity by localizing", "trafficking specificity by localizing to", "specificity by localizing to the", "by localizing to the membranes", "localizing to the membranes of", "to the membranes of different", "the membranes of different endocytic", "membranes of different endocytic compartments", "of different endocytic compartments and", "different endocytic compartments and interacting", "endocytic compartments and interacting with", "compartments and interacting with effectors", "and interacting with effectors such", "interacting with effectors such as", "with effectors such as sorting", "effectors such as sorting adaptors", "as sorting adaptors tethering", "sorting adaptors tethering factors", "factors kinases phosphatases", "kinases phosphatases and tubular", "phosphatases and tubular vesicular cargo", "tubular vesicular cargo reviewed", "vesicular cargo reviewed in", "cargo reviewed in stenmark", "reviewed in stenmark et al", "stenmark et al 2009", "al 2009 wandinger", "2009 wandinger ness and", "ness and zerial 2014", "and zerial 2014 .", "zerial 2014 . rab", "2014 . rab localization depends", ". rab localization depends on", "rab localization depends on a", "localization depends on a number", "depends on a number of", "on a number of factors", "a number of factors including", "number of factors including c", "of factors including c terminal", "factors including c terminal prenylation", "c terminal prenylation the", "terminal prenylation the sequence", "prenylation the sequence of", "the sequence of an upstream", "sequence of an upstream hypervariable", "of an upstream hypervariable regions", "an upstream hypervariable regions and", "upstream hypervariable regions and what", "hypervariable regions and what nucleotide", "regions and what nucleotide is", "and what nucleotide is bound", "nucleotide is bound chavrier", "is bound chavrier et", "bound chavrier et al", "chavrier et al 1991", "al 1991 ullrich", "1991 ullrich et al", "ullrich et al 1993", "al 1993 soldati", "1993 soldati et al", "soldati et al 1994", "al 1994 farnsworth", "1994 farnsworth et al", "farnsworth et al 1994", "al 1994 seabra", "1994 seabra 1996", "seabra 1996 wu", "1996 wu et al", "wu et al 2010", "al 2010 reviewed", "2010 reviewed in stenmark", "reviewed in stenmark 2009", "stenmark 2009 wandinger", "zerial 2014 . in", "2014 . in the active", "in the active gtp", "the active gtp bound", "active gtp bound form", "gtp bound form prenylated", "bound form prenylated rab", "form prenylated rab proteins", "prenylated rab proteins are membrane", "rab proteins are membrane associated", "are membrane associated while", "membrane associated while in", "associated while in the", "while in the inactive gdp", "in the inactive gdp bound", "the inactive gdp bound form", "gdp bound form rabs", "bound form rabs are", "form rabs are extracted", "rabs are extracted from the", "are extracted from the target", "extracted from the target membrane", "from the target membrane and", "the target membrane and exist", "target membrane and exist in", "membrane and exist in a", "and exist in a soluble", "exist in a soluble form", "in a soluble form in", "a soluble form in complex", "soluble form in complex with", "form in complex with gdp", "in complex with gdp dissociation", "complex with gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "gdis ullrich et", "al 1994 gavriljuk", "1994 gavriljuk et al", "gavriljuk et al 2103", "et al 2103 .", "al 2103 . conversion", "2103 . conversion between the", ". conversion between the inactive", "conversion between the inactive and", "between the inactive and active", "the inactive and active form", "inactive and active form relies", "and active form relies on", "active form relies on the", "form relies on the activities", "relies on the activities of", "on the activities of rab", "the activities of rab guanine", "activities of rab guanine nucleotide", "of rab guanine nucleotide exchange", "rab guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "factors gefs and", "gefs and gtpase activating", "gtpase activating proteins gaps", "gaps yoshimura et", "yoshimura et al 2010", "al 2010 wu", "2010 wu et al", "wu et al 2011", "al 2011 pan", "2011 pan et al", "pan et al 2006", "al 2006 frasa", "2006 frasa et al", "frasa et al 2012", "al 2012 reviewed", "2012 reviewed in stenmark", "and zerial 2014 .
newly", "zerial 2014 .
newly synthesized", "2014 .
newly synthesized rabs are", ".
newly synthesized rabs are bound", "synthesized rabs are bound by", "rabs are bound by a", "are bound by a rab", "bound by a rab escort", "by a rab escort protein", "rab escort protein chm", "protein chm also", "chm also known as", "known as rep1 or", "as rep1 or chml", "rep2 alexandrov et", "alexandrov et al 1994", "al 1994 shen", "1994 shen and seabra", "shen and seabra 1996", "and seabra 1996 .", "seabra 1996 . chm/rep", "1996 . chm/rep proteins are", ". chm/rep proteins are the", "chm/rep proteins are the substrate", "proteins are the substrate binding", "are the substrate binding component", "the substrate binding component of", "substrate binding component of the", "binding component of the trimeric", "component of the trimeric rab", "of the trimeric rab geranylgeranyltransferase", "the trimeric rab geranylgeranyltransferase enzyme", "rab geranylgeranyltransferase enzyme ggtaseii", "enzyme ggtaseii along", "ggtaseii along with the", "along with the two catalytic", "with the two catalytic subunits", "the two catalytic subunits rabggta", "two catalytic subunits rabggta and", "catalytic subunits rabggta and rabggtb", "rabggta and rabggtb reviewed", "and rabggtb reviewed in", "reviewed in gutkowska and", "in gutkowska and swiezewska", "gutkowska and swiezewska 2012", "swiezewska 2012 palsuledesai", "2012 palsuledesai and distefano", "palsuledesai and distefano 2015", "and distefano 2015 .", "distefano 2015 . rep", "2015 . rep proteins recruit", ". rep proteins recruit the", "rep proteins recruit the unmodified", "proteins recruit the unmodified rab", "recruit the unmodified rab in", "the unmodified rab in its", "unmodified rab in its gdp", "rab in its gdp bound", "in its gdp bound state", "its gdp bound state to", "gdp bound state to the", "bound state to the ggtase", "state to the ggtase for", "to the ggtase for sequential", "the ggtase for sequential geranylgeranylation", "ggtase for sequential geranylgeranylation at", "for sequential geranylgeranylation at one", "sequential geranylgeranylation at one or", "geranylgeranylation at one or two", "at one or two c", "one or two c terminal", "or two c terminal cysteine", "two c terminal cysteine residues", "terminal cysteine residues alexandrov", "cysteine residues alexandrov et", "residues alexandrov et al", "1994 seabra et al", "et al 1996 shen", "al 1996 shen and", "1996 shen and seabra", "seabra 1996 baron", "1996 baron and seabra", "baron and seabra 2008", "and seabra 2008 .", "seabra 2008 . after", ". after geranylgeranylation chm/rep", "after geranylgeranylation chm/rep proteins", "geranylgeranylation chm/rep proteins remain", "chm/rep proteins remain in complex", "proteins remain in complex with", "remain in complex with the", "in complex with the geranylgeranylated", "complex with the geranylgeranylated rab", "with the geranylgeranylated rab and", "the geranylgeranylated rab and escort", "geranylgeranylated rab and escort it", "rab and escort it to", "and escort it to its", "escort it to its target", "it to its target membrane", "its target membrane where", "target membrane where its", "membrane where its activity", "where its activity is regulated", "its activity is regulated by", "activity is regulated by gaps", "regulated by gaps gefs", "gaps gefs gdis", "gefs gdis and membrane", "gdis and membrane bound gdi", "and membrane bound gdi displacement", "membrane bound gdi displacement factors", "gdi displacement factors gdfs", "gdfs sivars et", "sivars et al 2003", "al 2003 reviewed", "2003 reviewed in stenmark" ] }, { "record_id": "GLY_000594_1_624", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8874081", "r hsa", "hsa 8874081", "r hsa 8874081" ] }, { "record_id": "GLY_000594_1_624", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "met activates", "activates ptk2", "ptk2 signaling", "met activates ptk2", "activates ptk2 signaling", "met activates ptk2 signaling", "met 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a", ".
a potential", "potential coreceptor", "coreceptor role", "role of", "of cd44", "cd44 in", "in inlb", "mediated met", "met activation", "activation is", "is contradictory", "jung et", "al. 2009", "dortet et", "inlb a", "a cell wall", "cell wall protein", "wall protein of", "protein of listeria", "monocytogenes binds", "binds met receptor", "receptor acting", "acting as an", "as an hgf", "an hgf agonist", "agonist shen", "shen et al.", "et al. 2000", "2000 veiga", "veiga and cossart", "and cossart 2005", "cossart 2005 .", "2005 . listeria", ". listeria monocytogenes", "listeria monocytogenes inlb", "monocytogenes inlb proteins", "inlb proteins dimerize", "proteins dimerize through", "dimerize through their", "through their leucine", "their leucine rich", "leucine rich repeat", "rich repeat regions", "regions lrrs", "promoting dimerization of", "dimerization of met", "of met receptors", "met receptors that", "receptors that they", "that they are", "they are bound", "are bound to", "to ferraris", "ferraris et al.", "et al. 2010", "al. 2010 .", "2010 . inlb", ". inlb induced", "inlb induced met", "induced met receptor", "met receptor dimerization", "receptor dimerization is", "dimerization is followed", "is followed by", "followed by met", "by met trans", "met trans autophosphorylation", "trans autophosphorylation and", "autophosphorylation and activation", "and activation of", "activation of downstream", "of downstream ras/raf/mapk", "downstream ras/raf/mapk signaling", "ras/raf/mapk signaling and", "signaling and pi3k/akt", "and pi3k/akt signaling", "signaling niemann", "niemann et al.", "et al. 2007", "2007 ferraris", ". inlb bound", "inlb bound phosphorylated", "bound phosphorylated met", "phosphorylated met receptor", "met receptor recruits", "receptor recruits the", "recruits the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase cbl", "ligase cbl through", "cbl through grb2.", "through grb2. cbl", "grb2. cbl mediated", "cbl mediated monoubiquitination", "mediated monoubiquitination of", "monoubiquitination of inlb", "of inlb bound", "inlb bound met", "bound met promotes", "met promotes endocytosis", "promotes endocytosis and", "endocytosis and entry", "and entry of", "listeria monocytogenes to", "monocytogenes to host", "to host cells", "cells veiga", "2005 . cin85", ". cin85 is", "cin85 is necessary", "is necessary for", "necessary for endocytosis", "for endocytosis mediated", "endocytosis mediated entry", "listeria monocytogenes triggered", "monocytogenes triggered by", "triggered by cbl", "by cbl mediated", "monoubiquitination of met", "met veiga", "2005 . proteins", ". proteins involved", "proteins involved in", "involved in clathrin", "in clathrin mediated", "clathrin mediated endocytosis", "mediated endocytosis eps15", "endocytosis eps15 and", "eps15 and hgs", "hgs hrs", "hrs are", "are both necessary", "both necessary for", "necessary for cbl", "for cbl and", "cbl and met", "and met mediated", "met mediated entry", "into host cells", "cossart 2005 .
a", "2005 .
a potential", ".
a potential coreceptor", "potential coreceptor role", "coreceptor role of", "role of cd44", "of cd44 in", "cd44 in inlb", "in inlb mediated", "inlb mediated met", "mediated met activation", "met activation is", "activation is contradictory", "contradictory jung", "jung et al.", "et al. 2009", "2009 dortet", "dortet et al.", "inlb a cell", "a cell wall protein", "cell wall protein of", "wall protein of listeria", "protein of listeria monocytogenes", "listeria monocytogenes binds", "monocytogenes binds met", "met receptor acting", "receptor acting as", "acting as an hgf", "as an hgf agonist", "hgf agonist shen", "agonist shen et", "shen et al. 2000", "al. 2000 veiga", "2000 veiga and", "veiga and cossart 2005", "and cossart 2005 .", "cossart 2005 . listeria", "2005 . listeria monocytogenes", ". listeria monocytogenes inlb", "listeria monocytogenes inlb proteins", "monocytogenes inlb proteins dimerize", "inlb proteins dimerize through", "proteins dimerize through their", "dimerize through their leucine", "through their leucine rich", "their leucine rich repeat", "leucine rich repeat regions", "repeat regions lrrs", "lrrs promoting", "promoting dimerization of met", "dimerization of met receptors", "of met receptors that", "met receptors that they", "receptors that they are", "that they are bound", "they are bound to", "bound to ferraris", "to ferraris et", "ferraris et al. 2010", "et al. 2010 .", "al. 2010 . inlb", "2010 . inlb induced", ". inlb induced met", "inlb induced met receptor", "induced met receptor dimerization", "met receptor dimerization is", "receptor dimerization is followed", "dimerization is followed by", "is followed by met", "followed by met trans", "by met trans autophosphorylation", "met trans autophosphorylation and", "trans autophosphorylation and activation", "autophosphorylation and activation of", "and activation of downstream", "activation of downstream ras/raf/mapk", "of downstream ras/raf/mapk signaling", "downstream ras/raf/mapk signaling and", "ras/raf/mapk signaling and pi3k/akt", "signaling and pi3k/akt signaling", "pi3k/akt signaling niemann", "signaling niemann et", "niemann et al. 2007", "al. 2007 ferraris", "2007 ferraris et", "2010 . inlb bound", ". inlb bound phosphorylated", "inlb bound phosphorylated met", "bound phosphorylated met receptor", "phosphorylated met receptor recruits", "met receptor recruits the", "receptor recruits the e3", "recruits the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase cbl", "ubiquitin ligase cbl through", "ligase cbl through grb2.", "cbl through grb2. cbl", "through grb2. cbl mediated", "grb2. cbl mediated monoubiquitination", "cbl mediated monoubiquitination of", "mediated monoubiquitination of inlb", "monoubiquitination of inlb bound", "of inlb bound met", "inlb bound met promotes", "bound met promotes endocytosis", "met promotes endocytosis and", "promotes endocytosis and entry", "endocytosis and entry of", "and entry of listeria", "of listeria monocytogenes to", "listeria monocytogenes to host", "monocytogenes to host cells", "host cells veiga", "cells veiga and", "cossart 2005 . cin85", "2005 . cin85 is", ". cin85 is necessary", "cin85 is necessary for", "is necessary for endocytosis", "necessary for endocytosis mediated", "for endocytosis mediated entry", "endocytosis mediated entry of", "of listeria monocytogenes triggered", "listeria monocytogenes triggered by", "monocytogenes triggered by cbl", "triggered by cbl mediated", "by cbl mediated monoubiquitination", "mediated monoubiquitination of met", "of met veiga", "met veiga and", "cossart 2005 . proteins", "2005 . proteins involved", ". proteins involved in", "proteins involved in clathrin", "involved in clathrin mediated", "in clathrin mediated endocytosis", "clathrin mediated endocytosis eps15", "mediated endocytosis eps15 and", "endocytosis eps15 and hgs", "and hgs hrs", "hrs are both", "are both necessary for", "both necessary for cbl", "necessary for cbl and", "for cbl and met", "cbl and met mediated", "and met mediated entry", "met mediated entry of", "monocytogenes into host cells", "and cossart 2005 .
a", "cossart 2005 .
a potential", "2005 .
a potential coreceptor", ".
a potential coreceptor role", "potential coreceptor role of", "coreceptor role of cd44", "role of cd44 in", "of cd44 in inlb", "cd44 in inlb mediated", "in inlb mediated met", "inlb mediated met activation", "mediated met activation is", "met activation is contradictory", "is contradictory jung", "contradictory jung et", "jung et al. 2009", "al. 2009 dortet", "2009 dortet et", "dortet et al. 2010", "inlb a cell wall", "a cell wall protein of", "cell wall protein of listeria", "wall protein of listeria monocytogenes", "of listeria monocytogenes binds", "listeria monocytogenes binds met", "monocytogenes binds met receptor", "binds met receptor acting", "met receptor acting as", "receptor acting as an", "acting as an hgf agonist", "an hgf agonist shen", "hgf agonist shen et", "agonist shen et al.", "et al. 2000 veiga", "al. 2000 veiga and", "2000 veiga and cossart", "veiga and cossart 2005 .", "and cossart 2005 . listeria", "cossart 2005 . listeria monocytogenes", "2005 . listeria monocytogenes inlb", ". listeria monocytogenes inlb proteins", "listeria monocytogenes inlb proteins dimerize", "monocytogenes inlb proteins dimerize through", "inlb proteins dimerize through their", "proteins dimerize through their leucine", "dimerize through their leucine rich", "through their leucine rich repeat", "their leucine rich repeat regions", "rich repeat regions lrrs", "lrrs promoting dimerization", "promoting dimerization of met receptors", "dimerization of met receptors that", "of met receptors that they", "met receptors that they are", "receptors that they are bound", "that they are bound to", "are bound to ferraris", "bound to ferraris et", "to ferraris et al.", "ferraris et al. 2010 .", "et al. 2010 . inlb", "al. 2010 . inlb induced", "2010 . inlb induced met", ". inlb induced met receptor", "inlb induced met receptor dimerization", "induced met receptor dimerization is", "met receptor dimerization is followed", "receptor dimerization is followed by", "dimerization is followed by met", "is followed by met trans", "followed by met trans autophosphorylation", "by met trans autophosphorylation and", "met trans autophosphorylation and activation", "trans autophosphorylation and activation of", "autophosphorylation and activation of downstream", "and activation of downstream ras/raf/mapk", "activation of downstream ras/raf/mapk signaling", "of downstream ras/raf/mapk signaling and", "downstream ras/raf/mapk signaling and pi3k/akt", "ras/raf/mapk signaling and pi3k/akt signaling", "and pi3k/akt signaling niemann", "pi3k/akt signaling niemann et", "signaling niemann et al.", "et al. 2007 ferraris", "al. 2007 ferraris et", "2007 ferraris et al.", "al. 2010 . inlb bound", "2010 . inlb bound phosphorylated", ". inlb bound phosphorylated met", "inlb bound phosphorylated met receptor", "bound phosphorylated met receptor recruits", "phosphorylated met receptor recruits the", "met receptor recruits the e3", "receptor recruits the e3 ubiquitin", "recruits the e3 ubiquitin ligase", "the e3 ubiquitin ligase cbl", "e3 ubiquitin ligase cbl through", "ubiquitin ligase cbl through grb2.", "ligase cbl through grb2. cbl", "cbl through grb2. cbl mediated", "through grb2. cbl mediated monoubiquitination", "grb2. cbl mediated monoubiquitination of", "cbl mediated monoubiquitination of inlb", "mediated monoubiquitination of inlb bound", "monoubiquitination of inlb bound met", "of inlb bound met promotes", "inlb bound met promotes endocytosis", "bound met promotes endocytosis and", "met promotes endocytosis and entry", "promotes endocytosis and entry of", "endocytosis and entry of listeria", "and entry of listeria monocytogenes", "entry of listeria monocytogenes to", "of listeria monocytogenes to host", "listeria monocytogenes to host cells", "to host cells veiga", "host cells veiga and", "cells veiga and cossart", "and cossart 2005 . cin85", "cossart 2005 . cin85 is", "2005 . cin85 is necessary", ". cin85 is necessary for", "cin85 is necessary for endocytosis", "is necessary for endocytosis mediated", "necessary for endocytosis mediated entry", "for endocytosis mediated entry of", "endocytosis mediated entry of listeria", "entry of listeria monocytogenes triggered", "of listeria monocytogenes triggered by", "listeria monocytogenes triggered by cbl", "monocytogenes triggered by cbl mediated", "triggered by cbl mediated monoubiquitination", "by cbl mediated monoubiquitination of", "cbl mediated monoubiquitination of met", "monoubiquitination of met veiga", "of met veiga and", "met veiga and cossart", "and cossart 2005 . proteins", "cossart 2005 . proteins involved", "2005 . proteins involved in", ". proteins involved in clathrin", "proteins involved in clathrin mediated", "involved in clathrin mediated endocytosis", "in clathrin mediated endocytosis eps15", "clathrin mediated endocytosis eps15 and", "mediated endocytosis eps15 and hgs", "eps15 and hgs hrs", "hgs hrs are", "hrs are both necessary", "are both necessary for cbl", "both necessary for cbl and", "necessary for cbl and met", "for cbl and met mediated", "cbl and met mediated entry", "and met mediated entry of", "met mediated entry of listeria", "listeria monocytogenes into host cells", "into host cells veiga", "veiga and cossart 2005 .
a", "and cossart 2005 .
a potential", "cossart 2005 .
a potential coreceptor", "2005 .
a potential coreceptor role", ".
a potential coreceptor role of", "potential coreceptor role of cd44", "coreceptor role of cd44 in", "role of cd44 in inlb", "of cd44 in inlb mediated", "cd44 in inlb mediated met", "in inlb mediated met activation", "inlb mediated met activation is", "mediated met activation is contradictory", "activation is contradictory jung", "is contradictory jung et", "contradictory jung et al.", "et al. 2009 dortet", "al. 2009 dortet et", "2009 dortet et al.", "dortet et al. 2010 ." ] }, { "record_id": "GLY_000594_1_626", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8876198", "r hsa", "hsa 8876198", "r hsa 8876198" ] }, { "record_id": "GLY_000594_1_626", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rab gefs", "gefs exchange", "exchange gtp", "gtp for", "for gdp", "gdp on", "on rabs", "rab gefs exchange", "gefs exchange gtp", "exchange gtp for", "gtp for gdp", "for gdp on", "gdp on rabs", "rab gefs exchange gtp", "gefs exchange gtp for", "exchange gtp for gdp", "gtp for gdp on", "for gdp on rabs", "rab gefs exchange gtp for", "gefs exchange gtp for gdp", "exchange gtp for gdp on", "gtp for gdp on rabs", "human cells", "cells have", "have more", "more than", "than 60", "60 rab", "rab proteins", "proteins that", "that are", "are key", "key regulators", "regulators of", "of intracellular", "intracellular membrane", "membrane trafficking.", "trafficking. these", "these small", "small gtpases", "gtpases contribute", "contribute to", "to trafficking", "trafficking specificity", "specificity by", "by localizing", "localizing to", "to the", "the membranes", "membranes of", "of different", "different organelles", "organelles and", "and interacting", "interacting with", "with effectors", "effectors such", "such as", "as sorting", "sorting adaptors", "tethering factors", "phosphatases and", "and tubular", "tubular vesicular", "vesicular cargo", "reviewed in", "in stenmark", "stenmark et", "et al", "wandinger ness", "ness and", "and zerial", "zhen and", "and stenmark", "2015 .", ".

rab", "

rab localization", "localization depends", "depends on", "on a", "a number", "number of", "of factors", "factors including", "including c", "c terminal", "terminal prenylation", "the sequence", "sequence of", "of upstream", "upstream hypervariable", "hypervariable regions", "regions and", "and what", "what nucleotide", "nucleotide is", "is bound", "as well", "well as", "as interaction", "interaction with", "with rab", "rab interacting", "interacting proteins", "chavrier et", "ullrich et", "soldati et", "farnsworth et", "wu et", "2014 .", "more recently", "the activity", "activity of", "of rab", "gefs has", "has also", "also been", "been implicated", "implicated in", "in regulating", "regulating the", "the localization", "localization of", "blumer et", "schoebel et", "cabrera and", "and ungermann", "in barr", "2015

in", "

in the", "the active", "gtp bound", "bound form", "proteins are", "are membrane", "membrane associated", "while in", "in the", "the inactive", "inactive gdp", "gdp bound", "rabs are", "are extracted", "extracted from", "from the", "the target", "target membrane", "membrane and", "and exist", "exist in", "in a", "a soluble", "soluble form", "form in", "in complex", "complex with", "with gdp", "gdp dissociation", "dissociation inhibitors", "gavriljuk et", "2013 .", ". conversion", "conversion between", "between the", "inactive and", "and active", "active form", "form relies", "relies on", "on the", "the activities", "activities of", "rab guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "and gtpase", "gtpase activating", "activating proteins", "yoshimura et", "pan et", "frasa et", "ishida et", "2016 .

newly", ".

newly synthesized", "synthesized rabs", "are bound", "bound to", "to a", "a rab", "rab escort", "escort protein", "also known", "known as", "as rep1", "or chml", "alexandrov et", "shen and", "and seabra", "1996 .", ". chm/rep", "chm/rep proteins", "are the", "the substrate", "substrate binding", "binding component", "component of", "of the", "the trimeric", "trimeric rab", "rab geranylgeranyltransferase", "geranylgeranyltransferase enzyme", "along with", "with the", "the two", "two catalytic", "catalytic subunits", "subunits rabggta", "rabggta and", "and rabggtb", "in gutkowska", "gutkowska and", "and swiezewska", "palsuledesai and", "and distefano", ". rep", "rep proteins", "proteins recruit", "recruit the", "the unmodified", "unmodified rab", "rab in", "in its", "its gdp", "bound state", "state to", "the ggtase", "ggtase for", "for sequential", "sequential geranylgeranylation", "geranylgeranylation at", "at one", "one or", "or two", "two c", "terminal cysteine", "cysteine residues", "seabra et", "al 1996", "baron and", "2008 .", ". after", "after geranylation", "proteins remain", "remain in", "the geranylated", "geranylated rab", "rab and", "and escort", "escort it", "it to", "to its", "its target", "where rab", "rab activity", "activity is", "is regulated", "regulated by", "by gaps", "gdis and", "and membrane", "membrane bound", "bound gdi", "gdi displacement", "displacement factors", "sivars et", "2014 .

unlike", ".

unlike the", "the rab", "rab gaps", "to date", "all contain", "contain a", "a shared", "shared tbc", "tbc domain", "gefs are", "are structurally", "structurally diverse", "diverse and", "and range", "range from", "from monomeric", "monomeric to", "to multisubunit", "multisubunit complexes", "in fukuda", "fukuda et", "cherfils and", "and zeghouf", "2016 .", "while many", "many gefs", "gefs contain", "contain one", "one of", "of three", "three conserved", "conserved gef", "gef domains", "domains identified", "identified to", "the denn", "differentially expressed", "expressed in", "in normal", "normal and", "and neoplastic", "neoplastic cell", "the vps9", "vps9 domain", "domain and", "and the", "the sec2", "sec2 domain", "other gefs", "gefs lack", "lack a", "a conserved", "conserved domain", "in ishida", ". based", "based on", "on sequence", "sequence conservation", "conservation and", "and subunit", "subunit organization", "gefs can", "can be", "be grouped", "grouped into", "into 6", "6 general", "general classes:", "classes: the", "the dennd", "dennd containing", "containing gefs", "vps9 containing", "both monomeric", "sec2 containing", "heterodimeric gef", "gef complexes", "complexes such", "as ric1:rgp1", "the multisubunit", "multisubunit trappc", "trappc gef", "and others", "barr and", "and lambright", "marat et", ". gefs", "gefs for", "for many", "many rabs", "rabs have", "have still", "still not", "not been", "been identified", "human cells have", "cells have more", "have more than", "more than 60", "than 60 rab", "60 rab proteins", "rab proteins that", "proteins that are", "that are key", "are key regulators", "key regulators of", "regulators of intracellular", "of intracellular membrane", "intracellular membrane trafficking.", "membrane trafficking. these", "trafficking. these small", "these small gtpases", "small gtpases contribute", "gtpases contribute to", "contribute to trafficking", "to trafficking specificity", "trafficking specificity by", "specificity by localizing", "by localizing to", "localizing to the", "to the membranes", "the membranes of", "membranes of different", "of different organelles", "different organelles and", "organelles and interacting", "and interacting with", "interacting with effectors", "with effectors such", "effectors such as", "such as sorting", "as sorting adaptors", "adaptors tethering", "factors kinases", "kinases phosphatases", "phosphatases and tubular", "and tubular vesicular", "tubular vesicular cargo", "cargo reviewed", "reviewed in stenmark", "in stenmark et", "stenmark et al", "al 2009", "2009 wandinger", "wandinger ness and", "ness and zerial", "zerial 2014", "2014 zhen", "zhen and stenmark", "stenmark 2015", "2015 .

rab", ".

rab localization", "

rab localization depends", "localization depends on", "depends on a", "on a number", "a number of", "number of factors", "of factors including", "factors including c", "including c terminal", "c terminal prenylation", "prenylation the", "the sequence of", "sequence of upstream", "of upstream hypervariable", "upstream hypervariable regions", "hypervariable regions and", "regions and what", "and what nucleotide", "what nucleotide is", "nucleotide is bound", "bound as", "as well as", "well as interaction", "as interaction with", "interaction with rab", "with rab interacting", "rab interacting proteins", "proteins chavrier", "chavrier et al", "al 1991", "1991 ullrich", "ullrich et al", "al 1993", "1993 soldati", "soldati et al", "al 1994", "1994 farnsworth", "farnsworth et al", "1994 seabra", "seabra 1996", "1996 wu", "wu et al", "al 2010", "2010 reviewed", "stenmark 2009", ". more", "recently the", "the activity of", "activity of rab", "of rab gefs", "rab gefs has", "gefs has also", "has also been", "also been implicated", "been implicated in", "implicated in regulating", "in regulating the", "regulating the localization", "the localization of", "localization of rab", "of rab proteins", "proteins blumer", "blumer et al", "al 2103", "2103 schoebel", "schoebel et al", "2009 cabrera", "cabrera and ungermann", "ungermann 2013", "2013 reviewed", "reviewed in barr", "barr 2013", "2013 zhen", "2015

in the", "

in the active", "active gtp", "gtp bound form", "form rab", "rab proteins are", "proteins are membrane", "are membrane associated", "associated while", "while in the", "in the inactive", "the inactive gdp", "inactive gdp bound", "gdp bound form", "form rabs", "rabs are extracted", "are extracted from", "extracted from the", "from the target", "the target membrane", "target membrane and", "membrane and exist", "and exist in", "exist in a", "in a soluble", "a soluble form", "soluble form in", "form in complex", "in complex with", "complex with gdp", "with gdp dissociation", "gdp dissociation inhibitors", "inhibitors gdis", "1994 gavriljuk", "gavriljuk et al", "al 2013", "2013 . conversion", ". conversion between", "conversion between the", "between the inactive", "the inactive and", "inactive and active", "and active form", "active form relies", "form relies on", "relies on the", "on the activities", "the activities of", "activities of rab", "of rab guanine", "rab guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factors", "factors gefs", "gefs and", "and gtpase activating", "gtpase activating proteins", "proteins gaps", "yoshimura et al", "2010 wu", "al 2011", "2011 pan", "pan et al", "al 2006", "2006 frasa", "frasa et al", "al 2012", "2012 reviewed", "2014 ishida", "ishida et al", "al 2016", "2016 .

newly synthesized", ".

newly synthesized rabs", "synthesized rabs are", "rabs are bound", "are bound to", "bound to a", "to a rab", "a rab escort", "rab escort protein", "protein chm", "chm also", "also known as", "known as rep1", "rep1 or", "chml rep2", "alexandrov et al", "1994 shen", "shen and seabra", "1996 . chm/rep", ". chm/rep proteins", "chm/rep proteins are", "proteins are the", "are the substrate", "the substrate binding", "substrate binding component", "binding component of", "component of the", "of the trimeric", "the trimeric rab", "trimeric rab geranylgeranyltransferase", "rab geranylgeranyltransferase enzyme", "enzyme ggtaseii", "ggtaseii along", "along with the", "with the two", "the two catalytic", "two catalytic subunits", "catalytic subunits rabggta", "subunits rabggta and", "rabggta and rabggtb", "rabggtb reviewed", "reviewed in gutkowska", "in gutkowska and", "gutkowska and swiezewska", "swiezewska 2012", "2012 palsuledesai", "palsuledesai and distefano", "distefano 2015", "2015 . rep", ". rep proteins", "rep proteins recruit", "proteins recruit the", "recruit the unmodified", "the unmodified rab", "unmodified rab in", "rab in its", "in its gdp", "its gdp bound", "gdp bound state", "bound state to", "state to the", "to the ggtase", "the ggtase for", "ggtase for sequential", "for sequential geranylgeranylation", "sequential geranylgeranylation at", "geranylgeranylation at one", "at one or", "one or two", "or two c", "two c terminal", "c terminal cysteine", "terminal cysteine residues", "residues alexandrov", "seabra et al", "et al 1996", "1996 shen", "1996 baron", "baron and seabra", "seabra 2008", "2008 . after", ". after geranylation", "geranylation chm/rep", "chm/rep proteins remain", "proteins remain in", "remain in complex", "complex with the", "with the geranylated", "the geranylated rab", "geranylated rab and", "rab and escort", "and escort it", "escort it to", "it to its", "to its target", "its target membrane", "membrane where", "where rab activity", "rab activity is", "activity is regulated", "is regulated by", "regulated by gaps", "gaps gefs", "gefs gdis", "gdis and membrane", "and membrane bound", "membrane bound gdi", "bound gdi displacement", "gdi displacement factors", "factors gdfs", "sivars et al", "al 2003", "2003 reviewed", "2014 .

unlike the", ".

unlike the rab", "the rab gaps", "gaps which", "which to", "date all", "all contain a", "contain a shared", "a shared tbc", "shared tbc domain", "domain rab", "rab gefs are", "gefs are structurally", "are structurally diverse", "structurally diverse and", "diverse and range", "and range from", "range from monomeric", "from monomeric to", "monomeric to multisubunit", "to multisubunit complexes", "complexes reviewed", "reviewed in fukuda", "in fukuda et", "fukuda et al", "2011 frasa", "2012 cherfils", "cherfils and zeghouf", "zeghouf 2013", "2013 ishida", ". while", "while many gefs", "many gefs contain", "gefs contain one", "contain one of", "one of three", "of three conserved", "three conserved gef", "conserved gef domains", "gef domains identified", "domains identified to", "identified to date", "denn differentially", "differentially expressed in", "expressed in normal", "in normal and", "normal and neoplastic", "and neoplastic cell", "cell domain", "domain the", "the vps9 domain", "vps9 domain and", "domain and the", "and the sec2", "the sec2 domain", "domain other", "other gefs lack", "gefs lack a", "lack a conserved", "a conserved domain", "domain reviewed", "reviewed in ishida", "in ishida et", "2016 . based", ". based on", "based on sequence", "on sequence conservation", "sequence conservation and", "conservation and subunit", "and subunit organization", "organization gefs", "gefs can be", "can be grouped", "be grouped into", "grouped into 6", "into 6 general", "6 general classes:", "general classes: the", "classes: the dennd", "the dennd containing", "dennd containing gefs", "gefs the", "the vps9 containing", "vps9 containing gefs", "gefs both", "the sec2 containing", "sec2 containing gefs", "gefs homodimeric", "heterodimeric gef complexes", "gef complexes such", "complexes such as", "such as ric1:rgp1", "ric1:rgp1 the", "the multisubunit trappc", "multisubunit trappc gef", "gef and", "others reviewed", "in barr and", "barr and lambright", "lambright 2010", "2010 marat", "marat et al", "2011 ishida", "2016 . gefs", ". gefs for", "gefs for many", "for many rabs", "many rabs have", "rabs have still", "have still not", "still not been", "not been identified", "identified however.", "human cells have more", "cells have more than", "have more than 60", "more than 60 rab", "than 60 rab proteins", "60 rab proteins that", "rab proteins that are", "proteins that are key", "that are key regulators", "are key regulators of", "key regulators of intracellular", "regulators of intracellular membrane", "of intracellular membrane trafficking.", "intracellular membrane trafficking. these", "membrane trafficking. these small", "trafficking. these small gtpases", "these small gtpases contribute", "small gtpases contribute to", "gtpases contribute to trafficking", "contribute to trafficking specificity", "to trafficking specificity by", "trafficking specificity by localizing", "specificity by localizing to", "by localizing to the", "localizing to the membranes", "to the membranes of", "the membranes of different", "membranes of different organelles", "of different organelles and", "different organelles and interacting", "organelles and interacting with", "and interacting with effectors", "interacting with effectors such", "with effectors such as", "effectors such as sorting", "such as sorting adaptors", "sorting adaptors tethering", "adaptors tethering factors", "tethering factors kinases", "kinases phosphatases and", "phosphatases and tubular vesicular", "and tubular vesicular cargo", "vesicular cargo reviewed", "cargo reviewed in", "reviewed in stenmark et", "in stenmark et al", "et al 2009", "2009 wandinger ness", "wandinger ness and zerial", "and zerial 2014", "2014 zhen and", "and stenmark 2015", "stenmark 2015 .", "2015 .

rab localization", ".

rab localization depends", "

rab localization depends on", "localization depends on a", "depends on a number", "on a number of", "a number of factors", "number of factors including", "of factors including c", "factors including c terminal", "including c terminal prenylation", "terminal prenylation the", "prenylation the sequence", "the sequence of upstream", "sequence of upstream hypervariable", "of upstream hypervariable regions", "upstream hypervariable regions and", "hypervariable regions and what", "regions and what nucleotide", "and what nucleotide is", "what nucleotide is bound", "is bound as", "bound as well", "as well as interaction", "well as interaction with", "as interaction with rab", "interaction with rab interacting", "with rab interacting proteins", "interacting proteins chavrier", "proteins chavrier et", "et al 1991", "1991 ullrich et", "et al 1993", "1993 soldati et", "et al 1994", "1994 farnsworth et", "1996 wu et", "et al 2010", "2010 reviewed in", "in stenmark 2009", "zerial 2014 .", "2014 . more", ". more recently", "more recently the", "recently the activity", "the activity of rab", "activity of rab gefs", "of rab gefs has", "rab gefs has also", "gefs has also been", "has also been implicated", "also been implicated in", "been implicated in regulating", "implicated in regulating the", "in regulating the localization", "regulating the localization of", "the localization of rab", "localization of rab proteins", "rab proteins blumer", "proteins blumer et", "et al 2103", "2103 schoebel et", "2009 cabrera and", "and ungermann 2013", "2013 reviewed in", "in barr 2013", "2013 zhen and", "stenmark 2015

in", "2015

in the active", "the active gtp", "active gtp bound", "bound form rab", "form rab proteins", "rab proteins are membrane", "proteins are membrane associated", "membrane associated while", "associated while in", "while in the inactive", "in the inactive gdp", "the inactive gdp bound", "inactive gdp bound form", "bound form rabs", "form rabs are", "rabs are extracted from", "are extracted from the", "extracted from the target", "from the target membrane", "the target membrane and", "target membrane and exist", "membrane and exist in", "and exist in a", "exist in a soluble", "in a soluble form", "a soluble form in", "soluble form in complex", "form in complex with", "in complex with gdp", "complex with gdp dissociation", "with gdp dissociation inhibitors", "dissociation inhibitors gdis", "gdis ullrich", "1994 gavriljuk et", "et al 2013", "al 2013 .", "2013 . conversion between", ". conversion between the", "conversion between the inactive", "between the inactive and", "the inactive and active", "inactive and active form", "and active form relies", "active form relies on", "form relies on the", "relies on the activities", "on the activities of", "the activities of rab", "activities of rab guanine", "of rab guanine nucleotide", "rab guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs and gtpase", "and gtpase activating proteins", "activating proteins gaps", "gaps yoshimura", "2010 wu et", "et al 2011", "2011 pan et", "et al 2006", "2006 frasa et", "et al 2012", "2012 reviewed in", "2014 ishida et", "et al 2016", "al 2016 .

newly", "2016 .

newly synthesized rabs", ".

newly synthesized rabs are", "synthesized rabs are bound", "rabs are bound to", "are bound to a", "bound to a rab", "to a rab escort", "a rab escort protein", "escort protein chm", "chm also known", "also known as rep1", "as rep1 or", "rep1 or chml", "or chml rep2", "rep2 alexandrov", "1994 shen and", "and seabra 1996", "seabra 1996 .", "1996 . chm/rep proteins", ". chm/rep proteins are", "chm/rep proteins are the", "proteins are the substrate", "are the substrate binding", "the substrate binding component", "substrate binding component of", "binding component of the", "component of the trimeric", "of the trimeric rab", "the trimeric rab geranylgeranyltransferase", "trimeric rab geranylgeranyltransferase enzyme", "geranylgeranyltransferase enzyme ggtaseii", "ggtaseii along with", "along with the two", "with the two catalytic", "the two catalytic subunits", "two catalytic subunits rabggta", "catalytic subunits rabggta and", "subunits rabggta and rabggtb", "and rabggtb reviewed", "rabggtb reviewed in", "reviewed in gutkowska and", "in gutkowska and swiezewska", "and swiezewska 2012", "2012 palsuledesai and", "and distefano 2015", "distefano 2015 .", "2015 . rep proteins", ". rep proteins recruit", "rep proteins recruit the", "proteins recruit the unmodified", "recruit the unmodified rab", "the unmodified rab in", "unmodified rab in its", "rab in its gdp", "in its gdp bound", "its gdp bound state", "gdp bound state to", "bound state to the", "state to the ggtase", "to the ggtase for", "the ggtase for sequential", "ggtase for sequential geranylgeranylation", "for sequential geranylgeranylation at", "sequential geranylgeranylation at one", "geranylgeranylation at one or", "at one or two", "one or two c", "or two c terminal", "two c terminal cysteine", "c terminal cysteine residues", "cysteine residues alexandrov", "residues alexandrov et", "1994 seabra et", "seabra et al 1996", "al 1996 shen", "1996 shen and", "1996 baron and", "and seabra 2008", "seabra 2008 .", "2008 . after geranylation", "after geranylation chm/rep", "geranylation chm/rep proteins", "chm/rep proteins remain in", "proteins remain in complex", "remain in complex with", "in complex with the", "complex with the geranylated", "with the geranylated rab", "the geranylated rab and", "geranylated rab and escort", "rab and escort it", "and escort it to", "escort it to its", "it to its target", "to its target membrane", "target membrane where", "membrane where rab", "where rab activity is", "rab activity is regulated", "activity is regulated by", "is regulated by gaps", "by gaps gefs", "gefs gdis and", "gdis and membrane bound", "and membrane bound gdi", "membrane bound gdi displacement", "bound gdi displacement factors", "displacement factors gdfs", "gdfs sivars", "et al 2003", "2003 reviewed in", "zerial 2014 .

unlike", "2014 .

unlike the rab", ".

unlike the rab gaps", "rab gaps which", "which to date", "to date all", "date all contain", "all contain a shared", "contain a shared tbc", "a shared tbc domain", "tbc domain rab", "domain rab gefs", "rab gefs are structurally", "gefs are structurally diverse", "are structurally diverse and", "structurally diverse and range", "diverse and range from", "and range from monomeric", "range from monomeric to", "from monomeric to multisubunit", "monomeric to multisubunit complexes", "multisubunit complexes reviewed", "complexes reviewed in", "reviewed in fukuda et", "in fukuda et al", "2011 frasa et", "2012 cherfils and", "and zeghouf 2013", "2013 ishida et", "al 2016 .", "2016 . while", ". while many", "while many gefs contain", "many gefs contain one", "gefs contain one of", "contain one of three", "one of three conserved", "of three conserved gef", "three conserved gef domains", "conserved gef domains identified", "gef domains identified to", "domains identified to date", "the denn differentially", "denn differentially expressed", "differentially expressed in normal", "expressed in normal and", "in normal and neoplastic", "normal and neoplastic cell", "neoplastic cell domain", "domain the vps9", "the vps9 domain and", "vps9 domain and the", "domain and the sec2", "and the sec2 domain", "sec2 domain other", "domain other gefs", "other gefs lack a", "gefs lack a conserved", "lack a conserved domain", "conserved domain reviewed", "domain reviewed in", "reviewed in ishida et", "in ishida et al", "2016 . based on", ". based on sequence", "based on sequence conservation", "on sequence conservation and", "sequence conservation and subunit", "conservation and subunit organization", "subunit organization gefs", "organization gefs can", "gefs can be grouped", "can be grouped into", "be grouped into 6", "grouped into 6 general", "into 6 general classes:", "6 general classes: the", "general classes: the dennd", "classes: the dennd containing", "the dennd containing gefs", "containing gefs the", "gefs the vps9", "the vps9 containing gefs", "containing gefs both", "gefs both monomeric", "monomeric the", "the sec2 containing gefs", "containing gefs homodimeric", "homodimeric heterodimeric", "heterodimeric gef complexes such", "gef complexes such as", "complexes such as ric1:rgp1", "as ric1:rgp1 the", "ric1:rgp1 the multisubunit", "the multisubunit trappc gef", "trappc gef and", "gef and others", "and others reviewed", "others reviewed in", "reviewed in barr and", "in barr and lambright", "and lambright 2010", "2010 marat et", "2011 ishida et", "2016 . gefs for", ". gefs for many", "gefs for many rabs", "for many rabs have", "many rabs have still", "rabs have still not", "have still not been", "still not been identified", "been identified however.", "human cells have more than", "cells have more than 60", "have more than 60 rab", "more than 60 rab proteins", "than 60 rab proteins that", "60 rab proteins that are", "rab proteins that are key", "proteins that are key regulators", "that are key regulators of", "are key regulators of intracellular", "key regulators of intracellular membrane", "regulators of intracellular membrane trafficking.", "of intracellular membrane trafficking. these", "intracellular membrane trafficking. these small", "membrane trafficking. these small gtpases", "trafficking. these small gtpases contribute", "these small gtpases contribute to", "small gtpases contribute to trafficking", "gtpases contribute to trafficking specificity", "contribute to trafficking specificity by", "to trafficking specificity by localizing", "trafficking specificity by localizing to", "specificity by localizing to the", "by localizing to the membranes", "localizing to the membranes of", "to the membranes of different", "the membranes of different organelles", "membranes of different organelles and", "of different organelles and interacting", "different organelles and interacting with", "organelles and interacting with effectors", "and interacting with effectors such", "interacting with effectors such as", "with effectors such as sorting", "effectors such as sorting adaptors", "as sorting adaptors tethering", "sorting adaptors tethering factors", "factors kinases phosphatases", "kinases phosphatases and tubular", "phosphatases and tubular vesicular cargo", "tubular vesicular cargo reviewed", "vesicular cargo reviewed in", "cargo reviewed in stenmark", "reviewed in stenmark et al", "stenmark et al 2009", "al 2009 wandinger", "2009 wandinger ness and", "ness and zerial 2014", "zerial 2014 zhen", "2014 zhen and stenmark", "zhen and stenmark 2015", "and stenmark 2015 .", "stenmark 2015 .

rab", "2015 .

rab localization depends", ".

rab localization depends on", "

rab localization depends on a", "localization depends on a number", "depends on a number of", "on a number of factors", "a number of factors including", "number of factors including c", "of factors including c terminal", "factors including c terminal prenylation", "c terminal prenylation the", "terminal prenylation the sequence", "prenylation the sequence of", "the sequence of upstream hypervariable", "sequence of upstream hypervariable regions", "of upstream hypervariable regions and", "upstream hypervariable regions and what", "hypervariable regions and what nucleotide", "regions and what nucleotide is", "and what nucleotide is bound", "nucleotide is bound as", "is bound as well", "bound as well as", "as well as interaction with", "well as interaction with rab", "as interaction with rab interacting", "interaction with rab interacting proteins", "rab interacting proteins chavrier", "interacting proteins chavrier et", "proteins chavrier et al", "chavrier et al 1991", "al 1991 ullrich", "1991 ullrich et al", "ullrich et al 1993", "al 1993 soldati", "1993 soldati et al", "soldati et al 1994", "al 1994 farnsworth", "1994 farnsworth et al", "farnsworth et al 1994", "al 1994 seabra", "1994 seabra 1996", "seabra 1996 wu", "1996 wu et al", "wu et al 2010", "al 2010 reviewed", "2010 reviewed in stenmark", "reviewed in stenmark 2009", "stenmark 2009 wandinger", "and zerial 2014 .", "2014 . more recently", "more recently the activity", "recently the activity of", "the activity of rab gefs", "activity of rab gefs has", "of rab gefs has also", "rab gefs has also been", "gefs has also been implicated", "has also been implicated in", "also been implicated in regulating", "been implicated in regulating the", "implicated in regulating the localization", "in regulating the localization of", "regulating the localization of rab", "the localization of rab proteins", "of rab proteins blumer", "rab proteins blumer et", "proteins blumer et al", "blumer et al 2103", "al 2103 schoebel", "2103 schoebel et al", "schoebel et al 2009", "al 2009 cabrera", "2009 cabrera and ungermann", "cabrera and ungermann 2013", "ungermann 2013 reviewed", "2013 reviewed in barr", "reviewed in barr 2013", "barr 2013 zhen", "2013 zhen and stenmark", "and stenmark 2015

in", "stenmark 2015

in the", "

in the active gtp", "the active gtp bound", "active gtp bound form", "gtp bound form rab", "bound form rab proteins", "form rab proteins are", "rab proteins are membrane associated", "are membrane associated while", "membrane associated while in", "associated while in the", "while in the inactive gdp", "in the inactive gdp bound", "the inactive gdp bound form", "gdp bound form rabs", "bound form rabs are", "form rabs are extracted", "rabs are extracted from the", "are extracted from the target", "extracted from the target membrane", "from the target membrane and", "the target membrane and exist", "target membrane and exist in", "membrane and exist in a", "and exist in a soluble", "exist in a soluble form", "in a soluble form in", "a soluble form in complex", "soluble form in complex with", "form in complex with gdp", "in complex with gdp dissociation", "complex with gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "gdis ullrich et", "al 1994 gavriljuk", "1994 gavriljuk et al", "gavriljuk et al 2013", "et al 2013 .", "al 2013 . conversion", "2013 . conversion between the", ". conversion between the inactive", "conversion between the inactive and", "between the inactive and active", "the inactive and active form", "inactive and active form relies", "and active form relies on", "active form relies on the", "form relies on the activities", "relies on the activities of", "on the activities of rab", "the activities of rab guanine", "activities of rab guanine nucleotide", "of rab guanine nucleotide exchange", "rab guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "factors gefs and", "gefs and gtpase activating", "gtpase activating proteins gaps", "gaps yoshimura et", "yoshimura et al 2010", "al 2010 wu", "2010 wu et al", "wu et al 2011", "al 2011 pan", "2011 pan et al", "pan et al 2006", "al 2006 frasa", "2006 frasa et al", "frasa et al 2012", "al 2012 reviewed", "2012 reviewed in stenmark", "zerial 2014 ishida", "2014 ishida et al", "ishida et al 2016", "et al 2016 .

newly", "al 2016 .

newly synthesized", "2016 .

newly synthesized rabs are", ".

newly synthesized rabs are bound", "synthesized rabs are bound to", "rabs are bound to a", "are bound to a rab", "bound to a rab escort", "to a rab escort protein", "rab escort protein chm", "protein chm also", "chm also known as", "known as rep1 or", "as rep1 or chml", "rep2 alexandrov et", "alexandrov et al 1994", "al 1994 shen", "1994 shen and seabra", "shen and seabra 1996", "and seabra 1996 .", "seabra 1996 . chm/rep", "1996 . chm/rep proteins are", ". chm/rep proteins are the", "chm/rep proteins are the substrate", "proteins are the substrate binding", "are the substrate binding component", "the substrate binding component of", "substrate binding component of the", "binding component of the trimeric", "component of the trimeric rab", "of the trimeric rab geranylgeranyltransferase", "the trimeric rab geranylgeranyltransferase enzyme", "rab geranylgeranyltransferase enzyme ggtaseii", "enzyme ggtaseii along", "ggtaseii along with the", "along with the two catalytic", "with the two catalytic subunits", "the two catalytic subunits rabggta", "two catalytic subunits rabggta and", "catalytic subunits rabggta and rabggtb", "rabggta and rabggtb reviewed", "and rabggtb reviewed in", "rabggtb reviewed in gutkowska", "reviewed in gutkowska and swiezewska", "gutkowska and swiezewska 2012", "swiezewska 2012 palsuledesai", "2012 palsuledesai and distefano", "palsuledesai and distefano 2015", "and distefano 2015 .", "distefano 2015 . rep", "2015 . rep proteins recruit", ". rep proteins recruit the", "rep proteins recruit the unmodified", "proteins recruit the unmodified rab", "recruit the unmodified rab in", "the unmodified rab in its", "unmodified rab in its gdp", "rab in its gdp bound", "in its gdp bound state", "its gdp bound state to", "gdp bound state to the", "bound state to the ggtase", "state to the ggtase for", "to the ggtase for sequential", "the ggtase for sequential geranylgeranylation", "ggtase for sequential geranylgeranylation at", "for sequential geranylgeranylation at one", "sequential geranylgeranylation at one or", "geranylgeranylation at one or two", "at one or two c", "one or two c terminal", "or two c terminal cysteine", "two c terminal cysteine residues", "terminal cysteine residues alexandrov", "cysteine residues alexandrov et", "residues alexandrov et al", "1994 seabra et al", "et al 1996 shen", "al 1996 shen and", "1996 shen and seabra", "seabra 1996 baron", "1996 baron and seabra", "baron and seabra 2008", "and seabra 2008 .", "seabra 2008 . after", ". after geranylation chm/rep", "after geranylation chm/rep proteins", "geranylation chm/rep proteins remain", "chm/rep proteins remain in complex", "proteins remain in complex with", "remain in complex with the", "in complex with the geranylated", "complex with the geranylated rab", "with the geranylated rab and", "the geranylated rab and escort", "geranylated rab and escort it", "rab and escort it to", "and escort it to its", "escort it to its target", "it to its target membrane", "its target membrane where", "target membrane where rab", "membrane where rab activity", "where rab activity is regulated", "rab activity is regulated by", "activity is regulated by gaps", "regulated by gaps gefs", "gaps gefs gdis", "gefs gdis and membrane", "gdis and membrane bound gdi", "and membrane bound gdi displacement", "membrane bound gdi displacement factors", "gdi displacement factors gdfs", "gdfs sivars et", "sivars et al 2003", "al 2003 reviewed", "2003 reviewed in stenmark", "and zerial 2014 .

unlike", "zerial 2014 .

unlike the", "2014 .

unlike the rab gaps", "the rab gaps which", "gaps which to", "to date all contain", "date all contain a", "all contain a shared tbc", "contain a shared tbc domain", "shared tbc domain rab", "tbc domain rab gefs", "domain rab gefs are", "rab gefs are structurally diverse", "gefs are structurally diverse and", "are structurally diverse and range", "structurally diverse and range from", "diverse and range from monomeric", "and range from monomeric to", "range from monomeric to multisubunit", "from monomeric to multisubunit complexes", "to multisubunit complexes reviewed", "multisubunit complexes reviewed in", "complexes reviewed in fukuda", "reviewed in fukuda et al", "fukuda et al 2011", "al 2011 frasa", "2011 frasa et al", "al 2012 cherfils", "2012 cherfils and zeghouf", "cherfils and zeghouf 2013", "zeghouf 2013 ishida", "2013 ishida et al", "et al 2016 .", "2016 . while many", ". while many gefs", "while many gefs contain one", "many gefs contain one of", "gefs contain one of three", "contain one of three conserved", "one of three conserved gef", "of three conserved gef domains", "three conserved gef domains identified", "conserved gef domains identified to", "gef domains identified to date", "date the", "the denn differentially expressed", "denn differentially expressed in", "differentially expressed in normal and", "expressed in normal and neoplastic", "in normal and neoplastic cell", "and neoplastic cell domain", "cell domain the", "domain the vps9 domain", "the vps9 domain and the", "vps9 domain and the sec2", "domain and the sec2 domain", "the sec2 domain other", "sec2 domain other gefs", "domain other gefs lack", "other gefs lack a conserved", "gefs lack a conserved domain", "a conserved domain reviewed", "conserved domain reviewed in", "domain reviewed in ishida", "reviewed in ishida et al", "al 2016 . based", "2016 . based on sequence", ". based on sequence conservation", "based on sequence conservation and", "on sequence conservation and subunit", "sequence conservation and subunit organization", "and subunit organization gefs", "subunit organization gefs can", "organization gefs can be", "gefs can be grouped into", "can be grouped into 6", "be grouped into 6 general", "grouped into 6 general classes:", "into 6 general classes: the", "6 general classes: the dennd", "general classes: the dennd containing", "classes: the dennd containing gefs", "dennd containing gefs the", "containing gefs the vps9", "gefs the vps9 containing", "vps9 containing gefs both", "containing gefs both monomeric", "both monomeric the", "monomeric the sec2", "sec2 containing gefs homodimeric", "homodimeric heterodimeric gef", "heterodimeric gef complexes such as", "gef complexes such as ric1:rgp1", "such as ric1:rgp1 the", "as ric1:rgp1 the multisubunit", "ric1:rgp1 the multisubunit trappc", "multisubunit trappc gef and", "trappc gef and others", "and others reviewed in", "others reviewed in barr", "reviewed in barr and lambright", "barr and lambright 2010", "lambright 2010 marat", "2010 marat et al", "marat et al 2011", "al 2011 ishida", "2011 ishida et al", "al 2016 . gefs", "2016 . gefs for many", ". gefs for many rabs", "gefs for many rabs have", "for many rabs have still", "many rabs have still not", "rabs have still not been", "have still not been identified", "not been identified however." ] }, { "record_id": "GLY_000594_1_627", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8878166", "r hsa", "hsa 8878166", "r hsa 8878166" ] }, { "record_id": "GLY_000594_1_627", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation by", "by runx2", "transcriptional regulation by", "regulation by runx2", "transcriptional regulation by runx2", "cbfa1 or", "or aml3", "transcription factor", "similar to", "to other", "other runx", "runx family", "family members", "runx1 and", "and runx3", "can function", "function in", "in complex", "complex with", "with cbfb", "cbf beta", "kundu et", "et al.", "al. 2002", "yoshida et", "otto et", "2002 .", ". runx2", "runx2 mainly", "mainly regulates", "regulates transcription", "transcription of", "of genes", "genes involved", "involved in", "in skeletal", "skeletal development", "reviewed in", "in karsenty", "karsenty 2008", "2008 .", "runx2 is", "is involved", "in development", "development of", "of both", "both intramembraneous", "intramembraneous and", "and endochondral", "endochondral bones", "bones through", "through regulation", "regulation of", "of osteoblast", "osteoblast differentiation", "differentiation and", "and chondrocyte", "chondrocyte maturation", "respectively. runx2", "runx2 stimulates", "stimulates transcription", "of the", "the bglap", "bglap gene", "ducy and", "and karsenty", "karsenty 1995", "ducy et", "al. 1997", "which encodes", "encodes osteocalcin", "a bone", "bone derived", "derived hormone", "hormone which", "which is", "is one", "one of", "the most", "most abundant", "abundant non", "non collagenous", "collagenous proteins", "proteins of", "the bone", "bone extracellular", "extracellular matrix", "karsenty and", "and olson", "olson 2016", "2016 .", "runx2 directly", "directly controls", "controls the", "the expression", "expression of", "of most", "most genes", "genes associated", "associated with", "with osteoblast", "and function", "sato et", "al. 1998", "al. 1999", "roce et", "al. 2005", "2005 .", "runx2 mediated", "mediated transcriptional", "of several", "several genes", "in gpcr", "g protein", "protein coupled", "coupled receptor", "signaling is", "is implicated", "implicated in", "in the", "the control", "control of", "of growth", "growth of", "osteoblast progenitors", "teplyuk et", "al. 2009", "2009 .", "runx2 promotes", "promotes chondrocyte", "maturation by", "by stimulating", "stimulating transcription", "the ihh", "ihh gene", "encoding indian", "indian hedgehog", "takeda et", "al. 2001", "al. 2004", "2004 .", ". germline", "germline loss", "loss of", "of function", "function mutations", "mutations of", "the runx2", "runx2 gene", "gene are", "are associated", "with cleidocranial", "cleidocranial dysplasia", "dysplasia syndrome", "an autosomal", "autosomal skeletal", "skeletal disorder", "in jaruga", "jaruga et", "al. 2016", ". the", "the function", "function of", "of runx2", "is frequently", "frequently disrupted", "disrupted in", "in osteosarcoma", "in mortus", "mortus et", "al. 2014", "2014 .", ". vitamin", "vitamin d3", "d3 is", "in regulation", "of transcriptional", "transcriptional activity", "activity of", "the runx2:cbfb", "runx2:cbfb complex", "underwood et", "al. 2012", "2012 .

runx2", ".

runx2 expression", "expression is", "is regulated", "regulated by", "by estrogen", "estrogen signaling", "and runx2", "in breast", "breast cancer", "cancer development", "development and", "and metastasis", "in wysokinski", "wysokinski et", ". besides", "besides estrogen", "estrogen receptor", "receptor alpha", "and estrogen", "estrogen related", "related receptor", "kammerer et", "al. 2013", "runx2 transcription", "transcription is", "is also", "also regulated", "by twist1", "yang et", "al. 2011", "glucocorticoid receptor", "zhang et", "nkx3 2", "tribioli and", "and lufkin", "lufkin 1999", "lengner et", "robledo et", "lee et", "and msx2", "runx2 can", "can autoregulate", "by directly", "directly inhibiting", "inhibiting its", "its own", "own transcription", "drissi et", "al. 2000", "2000 .", ". several", "several e3", "e3 ubiquitin", "ubiquitin ligases", "ligases target", "target runx2", "runx2 for", "for proteasome", "proteasome mediated", "mediated degradation:", "degradation: stub1", "li et", "al. 2008", "zhao et", "al. 2003", "jones et", "al. 2006", "and skp2", "thacker et", "besides formation", "formation of", "of runx2:cbfb", "runx2:cbfb heterodimers", "by binding", "binding to", "to a", "a number", "number of", "of other", "other transcription", "transcription factors", "for example", "example sox9", "zhou et", "bialek et", "and rb1", "thomas et", "2001 .

runx2", ".

runx2 regulates", "regulates expression", "genes implicated", "in cell", "cell migration", "migration during", "during normal", "normal development", "and bone", "bone metastasis", "metastasis of", "of breast", "cancer cells.", "cells. runx2", "the itga5", "itga5 gene", "encoding integrin", "integrin alpha", "alpha 5", "and the", "the itgbl1", "itgbl1 gene", "integrin beta", "beta like", "like protein", "protein 1", "al. 2015", "2015 .", "mediated transcription", "the mmp13", "mmp13 gene", "encoding colagenase", "colagenase 3", "matrix metalloproteinase", "metalloproteinase 13", "is stimulated", "stimulated by", "by akt", "akt mediated", "mediated phosphorylation", "phosphorylation of", "pande et", "2013 .", "in positive", "positive regulation", "of akt", "akt signaling", "signaling by", "stimulating expression", "akt activating", "activating torc2", "torc2 complex", "complex components", "components mtor", "mtor and", "and rictor", "which may", "may contribute", "contribute to", "to survival", "survival of", "cancer cells", "tandon et", "2014 .

runx2", ".

runx2 inhibits", "inhibits cdkn1a", "cdkn1a transcription", "thus preventing", "preventing cdkn1a", "cdkn1a induced", "induced cell", "cell cycle", "cycle arrest.", "arrest. phosphorylation", "runx2 by", "by cdk4", "cdk4 in", "in response", "response to", "to high", "high glucose", "glucose enhances", "enhances runx2", "mediated repression", "repression of", "the cdkn1a", "cdkn1a gene", "gene in", "in endothelial", "endothelial cells", "pierce et", "2012 .", ". in", "in mice", "of cdkn1a", "cdkn1a may", "to the", "the development", "of acute", "acute myeloid", "myeloid leukemia", "kuo et", "can stimulate", "stimulate transcription", "the lgals3", "lgals3 gene", "encoding galectin", "galectin 3", "vladimirova et", ". galectin", "3 is", "is expressed", "expressed in", "in myeloid", "myeloid progenitors", "progenitors and", "and its", "its levels", "levels increase", "increase during", "during the", "the maturation", "maturation process", "le marer", "marer 2000", "2000 .

for", ".

for a", "a review", "review of", "runx2 function", "please refer", "refer to", "to long", "long 2012", "2012 and", "and ito", "ito et", "al. 2015.", "runx2 cbfa1", "cbfa1 or aml3", "aml3 transcription", "factor similar", "similar to other", "to other runx", "other runx family", "runx family members", "members runx1", "runx1 and runx3", "runx3 can", "can function in", "function in complex", "in complex with", "complex with cbfb", "cbfb cbf", "kundu et al.", "et al. 2002", "2002 yoshida", "yoshida et al.", "2002 otto", "otto et al.", "al. 2002 .", "2002 . runx2", ". runx2 mainly", "runx2 mainly regulates", "mainly regulates transcription", "regulates transcription of", "transcription of genes", "of genes involved", "genes involved in", "involved in skeletal", "in skeletal development", "development reviewed", "reviewed in karsenty", "in karsenty 2008", "karsenty 2008 .", "2008 . runx2", ". runx2 is", "runx2 is involved", "is involved in", "involved in development", "in development of", "development of both", "of both intramembraneous", "both intramembraneous and", "intramembraneous and endochondral", "and endochondral bones", "endochondral bones through", "bones through regulation", "through regulation of", "regulation of osteoblast", "of osteoblast differentiation", "osteoblast differentiation and", "differentiation and chondrocyte", "and chondrocyte maturation", "maturation respectively.", "respectively. runx2 stimulates", "runx2 stimulates transcription", "stimulates transcription of", "transcription of the", "of the bglap", "the bglap gene", "gene ducy", "ducy and karsenty", "and karsenty 1995", "1995 ducy", "ducy et al.", "et al. 1997", "which encodes osteocalcin", "osteocalcin a", "a bone derived", "bone derived hormone", "derived hormone which", "hormone which is", "which is one", "is one of", "one of the", "of the most", "the most abundant", "most abundant non", "abundant non collagenous", "non collagenous proteins", "collagenous proteins of", "proteins of the", "of the bone", "the bone extracellular", "bone extracellular matrix", "matrix reviewed", "in karsenty and", "karsenty and olson", "and olson 2016", "olson 2016 .", "2016 . runx2", ". runx2 directly", "runx2 directly controls", "directly controls the", "controls the expression", "the expression of", "expression of most", "of most genes", "most genes associated", "genes associated with", "associated with osteoblast", "with osteoblast differentiation", "differentiation and function", "function sato", "sato et al.", "et al. 1998", "1998 ducy", "et al. 1999", "1999 roce", "roce et al.", "et al. 2005", "al. 2005 .", "2005 . runx2", ". runx2 mediated", "runx2 mediated transcriptional", "mediated transcriptional regulation", "transcriptional regulation of", "regulation of several", "of several genes", "several genes involved", "involved in gpcr", "gpcr g", "g protein coupled", "protein coupled receptor", "receptor signaling", "signaling is implicated", "is implicated in", "implicated in the", "in the control", "the control of", "control of growth", "of growth of", "growth of osteoblast", "of osteoblast progenitors", "progenitors teplyuk", "teplyuk et al.", "et al. 2009", "al. 2009 .", "2009 . runx2", ". runx2 promotes", "runx2 promotes chondrocyte", "promotes chondrocyte maturation", "chondrocyte maturation by", "maturation by stimulating", "by stimulating transcription", "stimulating transcription of", "of the ihh", "the ihh gene", "gene encoding", "encoding indian hedgehog", "hedgehog takeda", "takeda et al.", "et al. 2001", "2001 yoshida", "et al. 2004", "al. 2004 .", "2004 . germline", ". germline loss", "germline loss of", "loss of function", "of function mutations", "function mutations of", "mutations of the", "of the runx2", "the runx2 gene", "runx2 gene are", "gene are associated", "are associated with", "associated with cleidocranial", "with cleidocranial dysplasia", "cleidocranial dysplasia syndrome", "syndrome ccd", "an autosomal skeletal", "autosomal skeletal disorder", "disorder reviewed", "reviewed in jaruga", "in jaruga et", "jaruga et al.", "et al. 2016", "al. 2016 .", "2016 . the", ". the function", "the function of", "function of runx2", "of runx2 is", "runx2 is frequently", "is frequently disrupted", "frequently disrupted in", "disrupted in osteosarcoma", "osteosarcoma reviewed", "reviewed in mortus", "in mortus et", "mortus et al.", "et al. 2014", "al. 2014 .", "2014 . vitamin", ". vitamin d3", "vitamin d3 is", "d3 is implicated", "implicated in regulation", "in regulation of", "regulation of transcriptional", "of transcriptional activity", "transcriptional activity of", "activity of the", "of the runx2:cbfb", "the runx2:cbfb complex", "complex underwood", "underwood et al.", "et al. 2012", "al. 2012 .

runx2", "2012 .

runx2 expression", ".

runx2 expression is", "expression is regulated", "is regulated by", "regulated by estrogen", "by estrogen signaling", "signaling and", "and runx2 is", "runx2 is implicated", "implicated in breast", "in breast cancer", "breast cancer development", "cancer development and", "development and metastasis", "metastasis reviewed", "reviewed in wysokinski", "in wysokinski et", "wysokinski et al.", "2014 . besides", ". besides estrogen", "besides estrogen receptor", "estrogen receptor alpha", "alpha esr1", "esr1 and", "and estrogen related", "estrogen related receptor", "related receptor alpha", "alpha erra", "kammerer et al.", "et al. 2013", "runx2 transcription is", "transcription is also", "is also regulated", "also regulated by", "regulated by twist1", "twist1 yang", "yang yang", "yang et al.", "et al. 2011", "receptor nr3c1", "zhang et al.", "2 bapx1", "tribioli and lufkin", "and lufkin 1999", "1999 lengner", "lengner et al.", "dlx5 robledo", "robledo et al.", "2002 lee", "lee et al.", "2005 and", "msx2 lee", ". runx2 can", "runx2 can autoregulate", "autoregulate by", "by directly inhibiting", "directly inhibiting its", "inhibiting its own", "its own transcription", "transcription drissi", "drissi et al.", "et al. 2000", "al. 2000 .", "2000 . several", ". several e3", "several e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases target", "ligases target runx2", "target runx2 for", "runx2 for proteasome", "for proteasome mediated", "proteasome mediated degradation:", "mediated degradation: stub1", "stub1 chip", "li et al.", "et al. 2008", "smurf1 zhao", "zhao et al.", "et al. 2003", "2003 yang", "wwp1 jones", "jones et al.", "et al. 2006", "skp2 thacker", "thacker et al.", "2016 . besides", ". besides formation", "besides formation of", "formation of runx2:cbfb", "of runx2:cbfb heterodimers", "heterodimers transcriptional", "activity of runx2", "runx2 is regulated", "regulated by binding", "by binding to", "binding to a", "to a number", "a number of", "number of other", "of other transcription", "other transcription factors", "factors for", "for example sox9", "sox9 zhou", "zhou et al.", "2006 twist1", "twist1 bialek", "bialek et al.", "2004 and", "rb1 thomas", "thomas et al.", "al. 2001 .

runx2", "2001 .

runx2 regulates", ".

runx2 regulates expression", "regulates expression of", "expression of several", "several genes implicated", "genes implicated in", "implicated in cell", "in cell migration", "cell migration during", "migration during normal", "during normal development", "normal development and", "development and bone", "and bone metastasis", "bone metastasis of", "metastasis of breast", "of breast cancer", "breast cancer cells.", "cancer cells. runx2", "cells. runx2 stimulates", "of the itga5", "the itga5 gene", "encoding integrin alpha", "integrin alpha 5", "5 li", "2016 and", "and the itgbl1", "the itgbl1 gene", "encoding integrin beta", "integrin beta like", "beta like protein", "like protein 1", "1 li", "et al. 2015", "al. 2015 .", "2015 . runx2", "runx2 mediated transcription", "mediated transcription of", "of the mmp13", "the mmp13 gene", "encoding colagenase 3", "3 matrix", "matrix metalloproteinase 13", "is stimulated by", "stimulated by akt", "by akt mediated", "akt mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of runx2", "runx2 pande", "pande et al.", "al. 2013 .", "2013 . runx2", "implicated in positive", "in positive regulation", "positive regulation of", "regulation of akt", "of akt signaling", "akt signaling by", "signaling by stimulating", "by stimulating expression", "stimulating expression of", "expression of akt", "of akt activating", "akt activating torc2", "activating torc2 complex", "torc2 complex components", "complex components mtor", "components mtor and", "mtor and rictor", "rictor which", "which may contribute", "may contribute to", "contribute to survival", "to survival of", "survival of breast", "breast cancer cells", "cells tandon", "tandon et al.", "al. 2014 .

runx2", "2014 .

runx2 inhibits", ".

runx2 inhibits cdkn1a", "inhibits cdkn1a transcription", "transcription thus", "thus preventing cdkn1a", "preventing cdkn1a induced", "cdkn1a induced cell", "induced cell cycle", "cell cycle arrest.", "cycle arrest. phosphorylation", "arrest. phosphorylation of", "of runx2 by", "runx2 by cdk4", "by cdk4 in", "cdk4 in response", "in response to", "response to high", "to high glucose", "high glucose enhances", "glucose enhances runx2", "enhances runx2 mediated", "runx2 mediated repression", "mediated repression of", "repression of the", "of the cdkn1a", "the cdkn1a gene", "cdkn1a gene in", "gene in endothelial", "in endothelial cells", "cells pierce", "pierce et al.", "al. 2012 .", "2012 . in", ". in mice", "mice runx2", "repression of cdkn1a", "of cdkn1a may", "cdkn1a may contribute", "contribute to the", "to the development", "the development of", "development of acute", "of acute myeloid", "acute myeloid leukemia", "leukemia aml", "kuo et al.", "runx2 can stimulate", "can stimulate transcription", "stimulate transcription of", "of the lgals3", "the lgals3 gene", "encoding galectin 3", "3 vladimirova", "vladimirova et al.", "2008 zhang", "2009 . galectin", ". galectin 3", "galectin 3 is", "3 is expressed", "is expressed in", "expressed in myeloid", "in myeloid progenitors", "myeloid progenitors and", "progenitors and its", "and its levels", "its levels increase", "levels increase during", "increase during the", "during the maturation", "the maturation process", "process le", "le marer 2000", "marer 2000 .

for", "2000 .

for a", ".

for a review", "a review of", "review of runx2", "of runx2 function", "function please", "please refer to", "refer to long", "to long 2012", "long 2012 and", "2012 and ito", "and ito et", "ito et al.", "et al. 2015.", "runx2 cbfa1 or", "or aml3 transcription", "aml3 transcription factor", "transcription factor similar", "factor similar to", "similar to other runx", "to other runx family", "other runx family members", "family members runx1", "members runx1 and", "and runx3 can", "runx3 can function", "can function in complex", "function in complex with", "in complex with cbfb", "with cbfb cbf", "cbfb cbf beta", "beta kundu", "kundu et al. 2002", "al. 2002 yoshida", "2002 yoshida et", "yoshida et al. 2002", "al. 2002 otto", "2002 otto et", "otto et al. 2002", "et al. 2002 .", "al. 2002 . runx2", "2002 . runx2 mainly", ". runx2 mainly regulates", "runx2 mainly regulates transcription", "mainly regulates transcription of", "regulates transcription of genes", "transcription of genes involved", "of genes involved in", "genes involved in skeletal", "involved in skeletal development", "skeletal development reviewed", "development reviewed in", "reviewed in karsenty 2008", "in karsenty 2008 .", "karsenty 2008 . runx2", "2008 . runx2 is", ". runx2 is involved", "runx2 is involved in", "is involved in development", "involved in development of", "in development of both", "development of both intramembraneous", "of both intramembraneous and", "both intramembraneous and endochondral", "intramembraneous and endochondral bones", "and endochondral bones through", "endochondral bones through regulation", "bones through regulation of", "through regulation of osteoblast", "regulation of osteoblast differentiation", "of osteoblast differentiation and", "osteoblast differentiation and chondrocyte", "differentiation and chondrocyte maturation", "chondrocyte maturation respectively.", "maturation respectively. runx2", "respectively. runx2 stimulates transcription", "runx2 stimulates transcription of", "stimulates transcription of the", "transcription of the bglap", "of the bglap gene", "bglap gene ducy", "gene ducy and", "ducy and karsenty 1995", "karsenty 1995 ducy", "1995 ducy et", "ducy et al. 1997", "1997 which", "encodes osteocalcin a", "osteocalcin a bone", "a bone derived hormone", "bone derived hormone which", "derived hormone which is", "hormone which is one", "which is one of", "is one of the", "one of the most", "of the most abundant", "the most abundant non", "most abundant non collagenous", "abundant non collagenous proteins", "non collagenous proteins of", "collagenous proteins of the", "proteins of the bone", "of the bone extracellular", "the bone extracellular matrix", "extracellular matrix reviewed", "matrix reviewed in", "reviewed in karsenty and", "in karsenty and olson", "karsenty and olson 2016", "and olson 2016 .", "olson 2016 . runx2", "2016 . runx2 directly", ". runx2 directly controls", "runx2 directly controls the", "directly controls the expression", "controls the expression of", "the expression of most", "expression of most genes", "of most genes associated", "most genes associated with", "genes associated with osteoblast", "associated with osteoblast differentiation", "with osteoblast differentiation and", "osteoblast differentiation and function", "and function sato", "function sato et", "sato et al. 1998", "al. 1998 ducy", "1998 ducy et", "ducy et al. 1999", "al. 1999 roce", "1999 roce et", "roce et al. 2005", "et al. 2005 .", "al. 2005 . runx2", "2005 . runx2 mediated", ". runx2 mediated transcriptional", "runx2 mediated transcriptional regulation", "mediated transcriptional regulation of", "transcriptional regulation of several", "regulation of several genes", "of several genes involved", "several genes involved in", "genes involved in gpcr", "in gpcr g", "gpcr g protein", "g protein coupled receptor", "coupled receptor signaling", "receptor signaling is", "signaling is implicated in", "is implicated in the", "implicated in the control", "in the control of", "the control of growth", "control of growth of", "of growth of osteoblast", "growth of osteoblast progenitors", "osteoblast progenitors teplyuk", "progenitors teplyuk et", "teplyuk et al. 2009", "et al. 2009 .", "al. 2009 . runx2", "2009 . runx2 promotes", ". runx2 promotes chondrocyte", "runx2 promotes chondrocyte maturation", "promotes chondrocyte maturation by", "chondrocyte maturation by stimulating", "maturation by stimulating transcription", "by stimulating transcription of", "stimulating transcription of the", "transcription of the ihh", "of the ihh gene", "ihh gene encoding", "gene encoding indian", "indian hedgehog takeda", "hedgehog takeda et", "takeda et al. 2001", "al. 2001 yoshida", "2001 yoshida et", "yoshida et al. 2004", "et al. 2004 .", "al. 2004 . germline", "2004 . germline loss", ". germline loss of", "germline loss of function", "loss of function mutations", "of function mutations of", "function mutations of the", "mutations of the runx2", "of the runx2 gene", "the runx2 gene are", "runx2 gene are associated", "gene are associated with", "are associated with cleidocranial", "associated with cleidocranial dysplasia", "with cleidocranial dysplasia syndrome", "dysplasia syndrome ccd", "ccd an", "an autosomal skeletal disorder", "skeletal disorder reviewed", "disorder reviewed in", "reviewed in jaruga et", "in jaruga et al.", "jaruga et al. 2016", "et al. 2016 .", "al. 2016 . the", "2016 . the function", ". the function of", "the function of runx2", "function of runx2 is", "of runx2 is frequently", "runx2 is frequently disrupted", "is frequently disrupted in", "frequently disrupted in osteosarcoma", "in osteosarcoma reviewed", "osteosarcoma reviewed in", "reviewed in mortus et", "in mortus et al.", "mortus et al. 2014", "et al. 2014 .", "al. 2014 . vitamin", "2014 . vitamin d3", ". vitamin d3 is", "vitamin d3 is implicated", "d3 is implicated in", "is implicated in regulation", "implicated in regulation of", "in regulation of transcriptional", "regulation of transcriptional activity", "of transcriptional activity of", "transcriptional activity of the", "activity of the runx2:cbfb", "of the runx2:cbfb complex", "runx2:cbfb complex underwood", "complex underwood et", "underwood et al. 2012", "et al. 2012 .

runx2", "al. 2012 .

runx2 expression", "2012 .

runx2 expression is", ".

runx2 expression is regulated", "expression is regulated by", "is regulated by estrogen", "regulated by estrogen signaling", "estrogen signaling and", "signaling and runx2", "and runx2 is implicated", "runx2 is implicated in", "is implicated in breast", "implicated in breast cancer", "in breast cancer development", "breast cancer development and", "cancer development and metastasis", "and metastasis reviewed", "metastasis reviewed in", "reviewed in wysokinski et", "in wysokinski et al.", "wysokinski et al. 2014", "al. 2014 . besides", "2014 . besides estrogen", ". besides estrogen receptor", "besides estrogen receptor alpha", "receptor alpha esr1", "esr1 and estrogen", "and estrogen related receptor", "estrogen related receptor alpha", "receptor alpha erra", "erra kammerer", "kammerer et al. 2013", "2013 runx2", "runx2 transcription is also", "transcription is also regulated", "is also regulated by", "also regulated by twist1", "by twist1 yang", "yang yang et", "yang et al. 2011", "2011 glucocorticoid", "glucocorticoid receptor nr3c1", "nr3c1 zhang", "zhang et al. 2012", "2012 nkx3", "nkx3 2 bapx1", "bapx1 tribioli", "tribioli and lufkin 1999", "lufkin 1999 lengner", "1999 lengner et", "lengner et al. 2005", "2005 dlx5", "dlx5 robledo et", "robledo et al. 2002", "al. 2002 lee", "2002 lee et", "lee et al. 2005", "al. 2005 and", "2005 and msx2", "and msx2 lee", "msx2 lee et", "2005 . runx2 can", ". runx2 can autoregulate", "can autoregulate by", "autoregulate by directly", "by directly inhibiting its", "directly inhibiting its own", "inhibiting its own transcription", "own transcription drissi", "transcription drissi et", "drissi et al. 2000", "et al. 2000 .", "al. 2000 . several", "2000 . several e3", ". several e3 ubiquitin", "several e3 ubiquitin ligases", "e3 ubiquitin ligases target", "ubiquitin ligases target runx2", "ligases target runx2 for", "target runx2 for proteasome", "runx2 for proteasome mediated", "for proteasome mediated degradation:", "proteasome mediated degradation: stub1", "degradation: stub1 chip", "chip li", "li et al. 2008", "2008 smurf1", "smurf1 zhao et", "zhao et al. 2003", "al. 2003 yang", "2003 yang et", "yang et al. 2014", "2014 wwp1", "wwp1 jones et", "jones et al. 2006", "2006 and", "and skp2 thacker", "skp2 thacker et", "thacker et al. 2016", "al. 2016 . besides", "2016 . besides formation", ". besides formation of", "besides formation of runx2:cbfb", "formation of runx2:cbfb heterodimers", "runx2:cbfb heterodimers transcriptional", "heterodimers transcriptional activity", "transcriptional activity of runx2", "activity of runx2 is", "of runx2 is regulated", "runx2 is regulated by", "is regulated by binding", "regulated by binding to", "by binding to a", "binding to a number", "to a number of", "a number of other", "number of other transcription", "of other transcription factors", "transcription factors for", "factors for example", "example sox9 zhou", "sox9 zhou et", "zhou et al. 2006", "al. 2006 twist1", "twist1 bialek et", "bialek et al. 2004", "al. 2004 and", "2004 and rb1", "and rb1 thomas", "rb1 thomas et", "thomas et al. 2001", "et al. 2001 .

runx2", "al. 2001 .

runx2 regulates", "2001 .

runx2 regulates expression", ".

runx2 regulates expression of", "regulates expression of several", "expression of several genes", "of several genes implicated", "several genes implicated in", "genes implicated in cell", "implicated in cell migration", "in cell migration during", "cell migration during normal", "migration during normal development", "during normal development and", "normal development and bone", "development and bone metastasis", "and bone metastasis of", "bone metastasis of breast", "metastasis of breast cancer", "of breast cancer cells.", "breast cancer cells. runx2", "cancer cells. runx2 stimulates", "cells. runx2 stimulates transcription", "transcription of the itga5", "of the itga5 gene", "itga5 gene encoding", "gene encoding integrin", "encoding integrin alpha 5", "alpha 5 li", "5 li et", "li et al. 2016", "al. 2016 and", "2016 and the", "and the itgbl1 gene", "itgbl1 gene encoding", "encoding integrin beta like", "integrin beta like protein", "beta like protein 1", "protein 1 li", "1 li et", "li et al. 2015", "et al. 2015 .", "al. 2015 . runx2", "2015 . runx2 mediated", ". runx2 mediated transcription", "runx2 mediated transcription of", "mediated transcription of the", "transcription of the mmp13", "of the mmp13 gene", "mmp13 gene encoding", "gene encoding colagenase", "colagenase 3 matrix", "3 matrix metalloproteinase", "13 is", "is stimulated by akt", "stimulated by akt mediated", "by akt mediated phosphorylation", "akt mediated phosphorylation of", "mediated phosphorylation of runx2", "of runx2 pande", "runx2 pande et", "pande et al. 2013", "et al. 2013 .", "al. 2013 . runx2", "2013 . runx2 is", ". runx2 is implicated", "is implicated in positive", "implicated in positive regulation", "in positive regulation of", "positive regulation of akt", "regulation of akt signaling", "of akt signaling by", "akt signaling by stimulating", "signaling by stimulating expression", "by stimulating expression of", "stimulating expression of akt", "expression of akt activating", "of akt activating torc2", "akt activating torc2 complex", "activating torc2 complex components", "torc2 complex components mtor", "complex components mtor and", "components mtor and rictor", "and rictor which", "rictor which may", "which may contribute to", "may contribute to survival", "contribute to survival of", "to survival of breast", "survival of breast cancer", "of breast cancer cells", "cancer cells tandon", "cells tandon et", "tandon et al. 2014", "et al. 2014 .

runx2", "al. 2014 .

runx2 inhibits", "2014 .

runx2 inhibits cdkn1a", ".

runx2 inhibits cdkn1a transcription", "cdkn1a transcription thus", "transcription thus preventing", "thus preventing cdkn1a induced", "preventing cdkn1a induced cell", "cdkn1a induced cell cycle", "induced cell cycle arrest.", "cell cycle arrest. phosphorylation", "cycle arrest. phosphorylation of", "arrest. phosphorylation of runx2", "phosphorylation of runx2 by", "of runx2 by cdk4", "runx2 by cdk4 in", "by cdk4 in response", "cdk4 in response to", "in response to high", "response to high glucose", "to high glucose enhances", "high glucose enhances runx2", "glucose enhances runx2 mediated", "enhances runx2 mediated repression", "runx2 mediated repression of", "mediated repression of the", "repression of the cdkn1a", "of the cdkn1a gene", "the cdkn1a gene in", "cdkn1a gene in endothelial", "gene in endothelial cells", "endothelial cells pierce", "cells pierce et", "pierce et al. 2012", "et al. 2012 .", "al. 2012 . in", "2012 . in mice", "in mice runx2", "mice runx2 mediated", "mediated repression of cdkn1a", "repression of cdkn1a may", "of cdkn1a may contribute", "cdkn1a may contribute to", "may contribute to the", "contribute to the development", "to the development of", "the development of acute", "development of acute myeloid", "of acute myeloid leukemia", "myeloid leukemia aml", "aml kuo", "kuo et al. 2009", "2009 . runx2 can", ". runx2 can stimulate", "runx2 can stimulate transcription", "can stimulate transcription of", "stimulate transcription of the", "transcription of the lgals3", "of the lgals3 gene", "lgals3 gene encoding", "gene encoding galectin", "galectin 3 vladimirova", "3 vladimirova et", "vladimirova et al. 2008", "al. 2008 zhang", "2008 zhang et", "zhang et al. 2009", "al. 2009 . galectin", "2009 . galectin 3", ". galectin 3 is", "galectin 3 is expressed", "3 is expressed in", "is expressed in myeloid", "expressed in myeloid progenitors", "in myeloid progenitors and", "myeloid progenitors and its", "progenitors and its levels", "and its levels increase", "its levels increase during", "levels increase during the", "increase during the maturation", "during the maturation process", "maturation process le", "process le marer", "le marer 2000 .

for", "marer 2000 .

for a", "2000 .

for a review", ".

for a review of", "a review of runx2", "review of runx2 function", "runx2 function please", "function please refer", "please refer to long", "refer to long 2012", "to long 2012 and", "long 2012 and ito", "2012 and ito et", "and ito et al.", "ito et al. 2015.", "runx2 cbfa1 or aml3", "cbfa1 or aml3 transcription", "or aml3 transcription factor", "transcription factor similar to", "factor similar to other", "similar to other runx family", "to other runx family members", "runx family members runx1", "family members runx1 and", "members runx1 and runx3", "runx1 and runx3 can", "and runx3 can function", "runx3 can function in", "can function in complex with", "function in complex with cbfb", "complex with cbfb cbf", "with cbfb cbf beta", "cbf beta kundu", "beta kundu et", "et al. 2002 yoshida", "al. 2002 yoshida et", "2002 yoshida et al.", "et al. 2002 otto", "al. 2002 otto et", "2002 otto et al.", "otto et al. 2002 .", "et al. 2002 . runx2", "al. 2002 . runx2 mainly", "2002 . runx2 mainly regulates", ". runx2 mainly regulates transcription", "runx2 mainly regulates transcription of", "mainly regulates transcription of genes", "regulates transcription of genes involved", "transcription of genes involved in", "of genes involved in skeletal", "genes involved in skeletal development", "in skeletal development reviewed", "skeletal development reviewed in", "development reviewed in karsenty", "reviewed in karsenty 2008 .", "in karsenty 2008 . runx2", "karsenty 2008 . runx2 is", "2008 . runx2 is involved", ". runx2 is involved in", "runx2 is involved in development", "is involved in development of", "involved in development of both", "in development of both intramembraneous", "development of both intramembraneous and", "of both intramembraneous and endochondral", "both intramembraneous and endochondral bones", "intramembraneous and endochondral bones through", "and endochondral bones through regulation", "endochondral bones through regulation of", "bones through regulation of osteoblast", "through regulation of osteoblast differentiation", "regulation of osteoblast differentiation and", "of osteoblast differentiation and chondrocyte", "osteoblast differentiation and chondrocyte maturation", "and chondrocyte maturation respectively.", "chondrocyte maturation respectively. runx2", "maturation respectively. runx2 stimulates", "respectively. runx2 stimulates transcription of", "runx2 stimulates transcription of the", "stimulates transcription of the bglap", "transcription of the bglap gene", "the bglap gene ducy", "bglap gene ducy and", "gene ducy and karsenty", "and karsenty 1995 ducy", "karsenty 1995 ducy et", "1995 ducy et al.", "al. 1997 which", "1997 which encodes", "which encodes osteocalcin a", "encodes osteocalcin a bone", "osteocalcin a bone derived", "a bone derived hormone which", "bone derived hormone which is", "derived hormone which is one", "hormone which is one of", "which is one of the", "is one of the most", "one of the most abundant", "of the most abundant non", "the most abundant non collagenous", "most abundant non collagenous proteins", "abundant non collagenous proteins of", "non collagenous proteins of the", "collagenous proteins of the bone", "proteins of the bone extracellular", "of the bone extracellular matrix", "bone extracellular matrix reviewed", "extracellular matrix reviewed in", "matrix reviewed in karsenty", "reviewed in karsenty and olson", "in karsenty and olson 2016", "karsenty and olson 2016 .", "and olson 2016 . runx2", "olson 2016 . runx2 directly", "2016 . runx2 directly controls", ". runx2 directly controls the", "runx2 directly controls the expression", "directly controls the expression of", "controls the expression of most", "the expression of most genes", "expression of most genes associated", "of most genes associated with", "most genes associated with osteoblast", "genes associated with osteoblast differentiation", "associated with osteoblast differentiation and", "with osteoblast differentiation and function", "differentiation and function sato", "and function sato et", "function sato et al.", "et al. 1998 ducy", "al. 1998 ducy et", "1998 ducy et al.", "et al. 1999 roce", "al. 1999 roce et", "1999 roce et al.", "roce et al. 2005 .", "et al. 2005 . runx2", "al. 2005 . runx2 mediated", "2005 . runx2 mediated transcriptional", ". runx2 mediated transcriptional regulation", "runx2 mediated transcriptional regulation of", "mediated transcriptional regulation of several", "transcriptional regulation of several genes", "regulation of several genes involved", "of several genes involved in", "several genes involved in gpcr", "involved in gpcr g", "in gpcr g protein", "gpcr g protein coupled", "protein coupled receptor signaling", "coupled receptor signaling is", "receptor signaling is implicated", "signaling is implicated in the", "is implicated in the control", "implicated in the control of", "in the control of growth", "the control of growth of", "control of growth of osteoblast", "of growth of osteoblast progenitors", "of osteoblast progenitors teplyuk", "osteoblast progenitors teplyuk et", "progenitors teplyuk et al.", "teplyuk et al. 2009 .", "et al. 2009 . runx2", "al. 2009 . runx2 promotes", "2009 . runx2 promotes chondrocyte", ". runx2 promotes chondrocyte maturation", "runx2 promotes chondrocyte maturation by", "promotes chondrocyte maturation by stimulating", "chondrocyte maturation by stimulating transcription", "maturation by stimulating transcription of", "by stimulating transcription of the", "stimulating transcription of the ihh", "transcription of the ihh gene", "the ihh gene encoding", "ihh gene encoding indian", "gene encoding indian hedgehog", "encoding indian hedgehog takeda", "indian hedgehog takeda et", "hedgehog takeda et al.", "et al. 2001 yoshida", "al. 2001 yoshida et", "2001 yoshida et al.", "yoshida et al. 2004 .", "et al. 2004 . germline", "al. 2004 . germline loss", "2004 . germline loss of", ". germline loss of function", "germline loss of function mutations", "loss of function mutations of", "of function mutations of the", "function mutations of the runx2", "mutations of the runx2 gene", "of the runx2 gene are", "the runx2 gene are associated", "runx2 gene are associated with", "gene are associated with cleidocranial", "are associated with cleidocranial dysplasia", "associated with cleidocranial dysplasia syndrome", "cleidocranial dysplasia syndrome ccd", "ccd an autosomal", "autosomal skeletal disorder reviewed", "skeletal disorder reviewed in", "disorder reviewed in jaruga", "reviewed in jaruga et al.", "in jaruga et al. 2016", "jaruga et al. 2016 .", "et al. 2016 . the", "al. 2016 . the function", "2016 . the function of", ". the function of runx2", "the function of runx2 is", "function of runx2 is frequently", "of runx2 is frequently disrupted", "runx2 is frequently disrupted in", "is frequently disrupted in osteosarcoma", "disrupted in osteosarcoma reviewed", "in osteosarcoma reviewed in", "osteosarcoma reviewed in mortus", "reviewed in mortus et al.", "in mortus et al. 2014", "mortus et al. 2014 .", "et al. 2014 . vitamin", "al. 2014 . vitamin d3", "2014 . vitamin d3 is", ". vitamin d3 is implicated", "vitamin d3 is implicated in", "d3 is implicated in regulation", "is implicated in regulation of", "implicated in regulation of transcriptional", "in regulation of transcriptional activity", "regulation of transcriptional activity of", "of transcriptional activity of the", "transcriptional activity of the runx2:cbfb", "activity of the runx2:cbfb complex", "the runx2:cbfb complex underwood", "runx2:cbfb complex underwood et", "complex underwood et al.", "underwood et al. 2012 .

runx2", "et al. 2012 .

runx2 expression", "al. 2012 .

runx2 expression is", "2012 .

runx2 expression is regulated", ".

runx2 expression is regulated by", "expression is regulated by estrogen", "is regulated by estrogen signaling", "by estrogen signaling and", "estrogen signaling and runx2", "signaling and runx2 is", "and runx2 is implicated in", "runx2 is implicated in breast", "is implicated in breast cancer", "implicated in breast cancer development", "in breast cancer development and", "breast cancer development and metastasis", "development and metastasis reviewed", "and metastasis reviewed in", "metastasis reviewed in wysokinski", "reviewed in wysokinski et al.", "in wysokinski et al. 2014", "wysokinski et al. 2014 .", "et al. 2014 . besides", "al. 2014 . besides estrogen", "2014 . besides estrogen receptor", ". besides estrogen receptor alpha", "estrogen receptor alpha esr1", "alpha esr1 and", "esr1 and estrogen related", "and estrogen related receptor alpha", "related receptor alpha erra", "erra kammerer et", "al. 2013 runx2", "2013 runx2 transcription", "runx2 transcription is also regulated", "transcription is also regulated by", "is also regulated by twist1", "regulated by twist1 yang", "twist1 yang yang", "yang yang et al.", "al. 2011 glucocorticoid", "2011 glucocorticoid receptor", "nr3c1 zhang et", "al. 2012 nkx3", "2012 nkx3 2", "bapx1 tribioli and", "and lufkin 1999 lengner", "lufkin 1999 lengner et", "1999 lengner et al.", "al. 2005 dlx5", "dlx5 robledo et al.", "et al. 2002 lee", "al. 2002 lee et", "2002 lee et al.", "et al. 2005 and", "al. 2005 and msx2", "and msx2 lee et", "msx2 lee et al.", "lee et al. 2005 .", "al. 2005 . runx2 can", "2005 . runx2 can autoregulate", "runx2 can autoregulate by", "can autoregulate by directly", "autoregulate by directly inhibiting", "by directly inhibiting its own", "directly inhibiting its own transcription", "its own transcription drissi", "own transcription drissi et", "transcription drissi et al.", "drissi et al. 2000 .", "et al. 2000 . several", "al. 2000 . several e3", "2000 . several e3 ubiquitin", ". several e3 ubiquitin ligases", "several e3 ubiquitin ligases target", "e3 ubiquitin ligases target runx2", "ubiquitin ligases target runx2 for", "ligases target runx2 for proteasome", "target runx2 for proteasome mediated", "runx2 for proteasome mediated degradation:", "for proteasome mediated degradation: stub1", "mediated degradation: stub1 chip", "chip li et", "al. 2008 smurf1", "smurf1 zhao et al.", "et al. 2003 yang", "al. 2003 yang et", "2003 yang et al.", "al. 2014 wwp1", "wwp1 jones et al.", "al. 2006 and", "2006 and skp2", "and skp2 thacker et", "skp2 thacker et al.", "thacker et al. 2016 .", "et al. 2016 . besides", "al. 2016 . besides formation", "2016 . besides formation of", ". besides formation of runx2:cbfb", "besides formation of runx2:cbfb heterodimers", "of runx2:cbfb heterodimers transcriptional", "runx2:cbfb heterodimers transcriptional activity", "heterodimers transcriptional activity of", "transcriptional activity of runx2 is", "activity of runx2 is regulated", "of runx2 is regulated by", "runx2 is regulated by binding", "is regulated by binding to", "regulated by binding to a", "by binding to a number", "binding to a number of", "to a number of other", "a number of other transcription", "number of other transcription factors", "other transcription factors for", "transcription factors for example", "factors for example sox9", "for example sox9 zhou", "example sox9 zhou et", "sox9 zhou et al.", "et al. 2006 twist1", "2006 twist1 bialek", "twist1 bialek et al.", "et al. 2004 and", "al. 2004 and rb1", "and rb1 thomas et", "rb1 thomas et al.", "thomas et al. 2001 .

runx2", "et al. 2001 .

runx2 regulates", "al. 2001 .

runx2 regulates expression", "2001 .

runx2 regulates expression of", ".

runx2 regulates expression of several", "regulates expression of several genes", "expression of several genes implicated", "of several genes implicated in", "several genes implicated in cell", "genes implicated in cell migration", "implicated in cell migration during", "in cell migration during normal", "cell migration during normal development", "migration during normal development and", "during normal development and bone", "normal development and bone metastasis", "development and bone metastasis of", "and bone metastasis of breast", "bone metastasis of breast cancer", "metastasis of breast cancer cells.", "of breast cancer cells. runx2", "breast cancer cells. runx2 stimulates", "cancer cells. runx2 stimulates transcription", "cells. runx2 stimulates transcription of", "stimulates transcription of the itga5", "transcription of the itga5 gene", "the itga5 gene encoding", "itga5 gene encoding integrin", "gene encoding integrin alpha", "integrin alpha 5 li", "alpha 5 li et", "5 li et al.", "et al. 2016 and", "al. 2016 and the", "2016 and the itgbl1", "the itgbl1 gene encoding", "itgbl1 gene encoding integrin", "gene encoding integrin beta", "encoding integrin beta like protein", "integrin beta like protein 1", "like protein 1 li", "protein 1 li et", "1 li et al.", "li et al. 2015 .", "et al. 2015 . runx2", "al. 2015 . runx2 mediated", "2015 . runx2 mediated transcription", ". runx2 mediated transcription of", "runx2 mediated transcription of the", "mediated transcription of the mmp13", "transcription of the mmp13 gene", "the mmp13 gene encoding", "mmp13 gene encoding colagenase", "gene encoding colagenase 3", "encoding colagenase 3 matrix", "colagenase 3 matrix metalloproteinase", "3 matrix metalloproteinase 13", "metalloproteinase 13 is", "13 is stimulated", "is stimulated by akt mediated", "stimulated by akt mediated phosphorylation", "by akt mediated phosphorylation of", "akt mediated phosphorylation of runx2", "phosphorylation of runx2 pande", "of runx2 pande et", "runx2 pande et al.", "pande et al. 2013 .", "et al. 2013 . runx2", "al. 2013 . runx2 is", "2013 . runx2 is implicated", ". runx2 is implicated in", "runx2 is implicated in positive", "is implicated in positive regulation", "implicated in positive regulation of", "in positive regulation of akt", "positive regulation of akt signaling", "regulation of akt signaling by", "of akt signaling by stimulating", "akt signaling by stimulating expression", "signaling by stimulating expression of", "by stimulating expression of akt", "stimulating expression of akt activating", "expression of akt activating torc2", "of akt activating torc2 complex", "akt activating torc2 complex components", "activating torc2 complex components mtor", "torc2 complex components mtor and", "complex components mtor and rictor", "mtor and rictor which", "and rictor which may", "rictor which may contribute", "which may contribute to survival", "may contribute to survival of", "contribute to survival of breast", "to survival of breast cancer", "survival of breast cancer cells", "breast cancer cells tandon", "cancer cells tandon et", "cells tandon et al.", "tandon et al. 2014 .

runx2", "et al. 2014 .

runx2 inhibits", "al. 2014 .

runx2 inhibits cdkn1a", "2014 .

runx2 inhibits cdkn1a transcription", "inhibits cdkn1a transcription thus", "cdkn1a transcription thus preventing", "transcription thus preventing cdkn1a", "thus preventing cdkn1a induced cell", "preventing cdkn1a induced cell cycle", "cdkn1a induced cell cycle arrest.", "induced cell cycle arrest. phosphorylation", "cell cycle arrest. phosphorylation of", "cycle arrest. phosphorylation of runx2", "arrest. phosphorylation of runx2 by", "phosphorylation of runx2 by cdk4", "of runx2 by cdk4 in", "runx2 by cdk4 in response", "by cdk4 in response to", "cdk4 in response to high", "in response to high glucose", "response to high glucose enhances", "to high glucose enhances runx2", "high glucose enhances runx2 mediated", "glucose enhances runx2 mediated repression", "enhances runx2 mediated repression of", "runx2 mediated repression of the", "mediated repression of the cdkn1a", "repression of the cdkn1a gene", "of the cdkn1a gene in", "the cdkn1a gene in endothelial", "cdkn1a gene in endothelial cells", "in endothelial cells pierce", "endothelial cells pierce et", "cells pierce et al.", "pierce et al. 2012 .", "et al. 2012 . in", "al. 2012 . in mice", ". in mice runx2", "in mice runx2 mediated", "mice runx2 mediated repression", "runx2 mediated repression of cdkn1a", "mediated repression of cdkn1a may", "repression of cdkn1a may contribute", "of cdkn1a may contribute to", "cdkn1a may contribute to the", "may contribute to the development", "contribute to the development of", "to the development of acute", "the development of acute myeloid", "development of acute myeloid leukemia", "acute myeloid leukemia aml", "aml kuo et", "kuo et al. 2009 .", "al. 2009 . runx2 can", "2009 . runx2 can stimulate", ". runx2 can stimulate transcription", "runx2 can stimulate transcription of", "can stimulate transcription of the", "stimulate transcription of the lgals3", "transcription of the lgals3 gene", "the lgals3 gene encoding", "lgals3 gene encoding galectin", "gene encoding galectin 3", "encoding galectin 3 vladimirova", "galectin 3 vladimirova et", "3 vladimirova et al.", "et al. 2008 zhang", "al. 2008 zhang et", "2008 zhang et al.", "zhang et al. 2009 .", "et al. 2009 . galectin", "al. 2009 . galectin 3", "2009 . galectin 3 is", ". galectin 3 is expressed", "galectin 3 is expressed in", "3 is expressed in myeloid", "is expressed in myeloid progenitors", "expressed in myeloid progenitors and", "in myeloid progenitors and its", "myeloid progenitors and its levels", "progenitors and its levels increase", "and its levels increase during", "its levels increase during the", "levels increase during the maturation", "increase during the maturation process", "the maturation process le", "maturation process le marer", "process le marer 2000", "le marer 2000 .

for a", "marer 2000 .

for a review", "2000 .

for a review of", ".

for a review of runx2", "a review of runx2 function", "of runx2 function please", "runx2 function please refer", "function please refer to", "please refer to long 2012", "refer to long 2012 and", "to long 2012 and ito", "long 2012 and ito et", "2012 and ito et al.", "and ito et al. 2015." ] }, { "record_id": "GLY_000594_1_628", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "888590", "r hsa", "hsa 888590", "r hsa 888590" ] }, { "record_id": "GLY_000594_1_628", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gaba synthesis", "reuptake and", "and degradation", "synthesis release", "release reuptake", "reuptake and degradation", "gaba synthesis release", "release reuptake and", "synthesis release reuptake", "release reuptake and degradation", "gaba is", "is a", "a major", "major inhibitory", "inhibitory neurotransmitter", "neurotransmitter in", "in the", "the mammalian", "mammalian central", 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complex", "the snare complex that", "snare complex that also", "complex that also includes", "that also includes snap25", "also includes snap25 and", "includes snap25 and syntaxin", "and syntaxin leading", "syntaxin leading to", "leading to synaptic vesicle", "to synaptic vesicle fusion.", "synaptic vesicle fusion. release", "vesicle fusion. release of", "fusion. release of gaba", "release of gaba in", "of gaba in the", "gaba in the synaptic", "in the synaptic cleft", "the synaptic cleft leads", "synaptic cleft leads to", "cleft leads to binding", "leads to binding of", "to binding of gaba", "binding of gaba by", "of gaba by the", "gaba by the gaba", "by the gaba receptors", "the gaba receptors and", "gaba receptors and post", "receptors and post ligand", "and post ligand binding", "post ligand binding events.", "gaba is a major inhibitory", "is a major inhibitory neurotransmitter", "a major inhibitory neurotransmitter in", "major inhibitory neurotransmitter in the", "inhibitory neurotransmitter in the mammalian", "neurotransmitter in the mammalian central", "in the mammalian central nervous", "the mammalian central nervous system.", "mammalian central nervous system. gaba", "central nervous system. gaba modulates", "nervous system. gaba modulates neuronal", "system. gaba modulates neuronal excitability", "gaba modulates neuronal excitability throughout", "modulates neuronal excitability throughout the", "neuronal excitability throughout the nervous", "excitability throughout the nervous system.", "throughout the nervous system. disruption", "the nervous system. disruption of", "nervous system. disruption of gaba", "system. disruption of gaba neurotransmission", "disruption of gaba neurotransmission leads", "of gaba neurotransmission leads to", "gaba neurotransmission leads to many", "neurotransmission leads to many neurological", "leads to many neurological diseases", "to many neurological diseases including", "many neurological diseases including epilepsy", "neurological diseases including epilepsy and", "diseases including epilepsy and a", "including epilepsy and a general", "epilepsy and a general anxiety", "and a general anxiety disorder.", "a general anxiety disorder. gaba", "general anxiety disorder. gaba is", "anxiety disorder. gaba is synthesized", "disorder. gaba is synthesized by", "gaba is synthesized by two", "is synthesized by two distinct", "synthesized by two distinct enzymes", "by two distinct enzymes gad67", "two distinct enzymes gad67 and", "distinct enzymes gad67 and gad65", "enzymes gad67 and gad65 that", "gad67 and gad65 that differ", "and gad65 that differ in", "gad65 that differ in their", "that differ in their cellular", "differ in their cellular localization", "their cellular localization functional", "cellular localization functional properties", "localization functional properties and", "functional properties and co factor", "properties and co factor requirements.", "and co factor requirements. gaba", "co factor requirements. gaba synthesized", "factor requirements. gaba synthesized by", "requirements. gaba synthesized by gad65", "gaba synthesized by gad65 is", "synthesized by gad65 is used", "by gad65 is used for", "gad65 is used for neurotransmission", "is used for neurotransmission whereas", "used for neurotransmission whereas gaba", "for neurotransmission whereas gaba synthesized", "neurotransmission whereas gaba synthesized by", "whereas gaba synthesized by gad67", "gaba synthesized by gad67 is", "synthesized by gad67 is used", "by gad67 is used for", "gad67 is used for processes", "is used for processes other", "used for processes other than", "for processes other than neurotransmission", "processes other than neurotransmission such", "other than neurotransmission such as", "than neurotransmission such as synaptogenesis", "neurotransmission such as synaptogenesis and", "such as synaptogenesis and protection", "as synaptogenesis and protection against", "synaptogenesis and protection against neuronal", "and protection against neuronal injury.", "protection against neuronal injury. gaba", "against neuronal injury. gaba is", "neuronal injury. gaba is loaded", "injury. gaba is loaded into", "gaba is loaded into synaptic", "is loaded into synaptic vesicle", "loaded into synaptic vesicle with", "into synaptic vesicle with the", "synaptic vesicle with the help", "vesicle with the help of", "with the help of vesicular", "the help of vesicular inhibitory", "help of vesicular inhibitory amino", "of vesicular inhibitory amino acid", "vesicular inhibitory amino acid transporter", "inhibitory amino acid transporter or", "amino acid transporter or vgat.", "acid transporter or vgat. gad65", "transporter or vgat. gad65 and", "or vgat. gad65 and vgat", "vgat. gad65 and vgat are", "gad65 and vgat are functionally", "and vgat are functionally linked", "vgat are functionally linked at", "are functionally linked at the", "functionally linked at the synaptic", "linked at the synaptic vesicle", "at the synaptic vesicle membrane", "the synaptic vesicle membrane and", "synaptic vesicle membrane and gaba", "vesicle membrane and gaba synthesized", "membrane and gaba synthesized by", "and gaba synthesized by gad65", "synthesized by gad65 is preferentially", "by gad65 is preferentially loaded", "gad65 is preferentially loaded into", "is preferentially loaded into the", "preferentially loaded into the synaptic", "loaded into the synaptic vesicle", "into the synaptic vesicle over", "the synaptic vesicle over gaba", "synaptic vesicle over gaba synthesized", "vesicle over gaba synthesized in", "over gaba synthesized in cytoplasm", "gaba synthesized in cytoplasm by", "synthesized in cytoplasm by gad67.the", "in cytoplasm by gad67.the gaba", "cytoplasm by gad67.the gaba loaded", "by gad67.the gaba loaded synaptic", "gad67.the gaba loaded synaptic vesicles", "gaba loaded synaptic vesicles are", "loaded synaptic vesicles are docked", "synaptic vesicles are docked at", "vesicles 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ligand binding events." ] }, { "record_id": "GLY_000594_1_629", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8931987", "r hsa", "hsa 8931987", "r hsa 8931987" ] }, { "record_id": "GLY_000594_1_629", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "runx1 regulates", "regulates estrogen", "estrogen receptor", "receptor mediated", "mediated transcription", "runx1 regulates estrogen", "regulates estrogen receptor", "estrogen receptor mediated", "receptor mediated transcription", "runx1 regulates estrogen receptor", "regulates estrogen receptor mediated", "estrogen receptor mediated transcription", "runx1 regulates estrogen receptor mediated", "regulates estrogen receptor mediated transcription", "the runx1:cbfb", "runx1:cbfb complex", "complex can", "can associate", "associate with", "with the", "the activated", "activated estrogen", "receptor alpha", "through direct", "direct interaction", 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"human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8935690", "r hsa", "hsa 8935690", "r hsa 8935690" ] }, { "record_id": "GLY_000594_1_630", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dietary carbohydrates", "and proteins", "proteins must", "must be", "be broken", "broken down", "down to", "to their", "their constituent", "constituent monosaccharides", "fatty acids", "acids and", "and sterols", "and amino", "amino acids", "before they", "they can", "can be", "be absorbed", "absorbed in", "in the", "the intestine.
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carbohydrates include", "into enterocytes.
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carbohydrates include starch", "enterocytes.
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megakaryocytic", "2013 .
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the", "2009 .
the runx1:cbfb", ".
the runx1:cbfb complex", "runx1:cbfb complex stimulates", "complex stimulates transcription", "stimulates transcription of", "transcription of the", "of the pf4", "the pf4 gene", "gene encoding", "encoding a component", "a component of", "component of platelet", "of platelet alpha", "platelet alpha granules", "granules aneja", "aneja et al.", "et al. 2011", "the nr4a3 gene", "gene associated", "associated with the", "with the familial", "the familial platelet", "familial platelet disorder", "disorder fpd", "bluteau et al.", "the prkcq gene", "associated with inherited", "with inherited thrombocytopenia", "thrombocytopenia jalagadugula", "jalagadugula et al.", "the myl9 gene", "gene involved", "involved in thrombopoiesis", "thrombopoiesis jalagadugula", "et al. 2010", "and the nfe2", "the nfe2 gene", "gene a", "a regulator of", "regulator of erythroid", "of erythroid and", "erythroid and megakaryocytic", "and megakaryocytic maturation", "megakaryocytic maturation and", "maturation and differentiation", "differentiation wang", "wang et al.", "al. 2010 .", "in human hematopoietic progenitors", "hematopoietic progenitors runx1", "progenitors runx1 and", "runx1 and its partner", "and its partner cbfb", "its partner cbfb are", "partner cbfb are up", "cbfb are up regulated", "are up regulated at", "up regulated at the", "regulated at the onset", "at the onset of", "the onset of megakaryocytic", "onset of megakaryocytic differentiation", "of megakaryocytic differentiation and", "megakaryocytic differentiation and down", "differentiation and down regulated", "and down regulated at", "down regulated at the", "the onset of erythroid", "onset of erythroid differentiation.", "of erythroid differentiation. the", "erythroid differentiation. the complex", "differentiation. the complex of", "the complex of runx1", "complex of runx1 and", "of runx1 and cbfb", "runx1 and cbfb cooperates", "and cbfb cooperates with", "cbfb cooperates with the", "cooperates with the transcription", "with the transcription factor", "the transcription factor gata1", "transcription factor gata1 in", "factor gata1 in the", "gata1 in the transactivation", "in the transactivation of", "the transactivation of megakaryocyte", "transactivation of megakaryocyte specific", "of megakaryocyte specific genes.", "megakaryocyte specific genes. in", "specific genes. in addition", "in addition runx1", "addition runx1 and", "runx1 and gata1 physically", "and gata1 physically interact", "physically interact elagib", "interact elagib et", "elagib et al. 2003", "2003 and", "and this interaction involves", "this interaction involves the", "interaction involves the zinc", "involves the zinc finger", "the zinc finger domain", "zinc finger domain of", "finger domain of gata1", "of gata1 xu", "gata1 xu et", "xu et al. 2006", "et al. 2006 .", "al. 2006 . other", "2006 . other components", ". other components of", "other components of the", "components of the runx1:cbfb", "of the runx1:cbfb activating", "the 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transcriptional", "the transcriptional repressor complex", "transcriptional repressor complex can", "repressor complex can form", "complex can form at", "can form at megakaryocytic", "form at megakaryocytic promoters", "megakaryocytic promoters as", "promoters as runx1", "as runx1 that is", "runx1 that is not", "that is not arginine", "is not arginine methylated", "not arginine methylated can", "arginine methylated can bind", "methylated can bind to", "can bind to sin3a/sin3b", "bind to sin3a/sin3b co", "to sin3a/sin3b co repressors", "co repressors zhao", "repressors zhao et", "zhao et al. 2008", "et al. 2008 .", "al. 2008 . besides", "2008 . besides sin3a/sin3b", "besides sin3a/sin3b the", "sin3a/sin3b the runx1:cbfb", "the runx1:cbfb repressor complex", "runx1:cbfb repressor complex at", "repressor complex at megakaryocytic", "at megakaryocytic promoters also", "megakaryocytic promoters also includes", "promoters also includes histone", "also includes histone deacetylase", "includes histone deacetylase hdac1", "histone deacetylase hdac1 and", "deacetylase hdac1 and histone", "hdac1 and histone arginine", "and histone arginine methyltransferase", "histone arginine methyltransferase prmt6", "methyltransferase prmt6 herglotz", "prmt6 herglotz et", "et al. 2013 .
megakaryocytic", "al. 2013 .
megakaryocytic promoters", "2013 .
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megakaryocytic promoters regulated by", "promoters regulated by the", "regulated by the described", "by the described runx1:cbfb", "the described runx1:cbfb activating", "described runx1:cbfb activating and", "runx1:cbfb activating and repressing", "activating and repressing complexes", "and repressing complexes include", "repressing complexes include itga2b", "include itga2b gp1ba", "gp1ba thbs1 and", "and mir27a herglotz", "mir27a herglotz et", "al. 2013 . itga2b", "2013 . itga2b is", ". itga2b is only", "itga2b is only expressed", "is only expressed in", "only expressed in maturing", "expressed in maturing megakaryocytes", "in maturing megakaryocytes and", "maturing megakaryocytes and platelets", "megakaryocytes and platelets and", "and platelets and is", "platelets and is involved", "and is involved in", "is involved in platelet", "involved in platelet aggregation", "platelet aggregation block", "aggregation block and", "block and poncz 1995", "and poncz 1995 .", "poncz 1995 . gp1ba", "1995 . gp1ba is", ". gp1ba is expressed", "gp1ba is expressed at", "is expressed at the", "expressed at the cell", "at the cell surface", "the cell surface membrane", "cell surface membrane of", "surface membrane of maturing", "membrane of maturing megakaryocytes", "of maturing megakaryocytes and", "and platelets and participates", "platelets and participates in", "and participates in formation", "participates in formation of", "in formation of platelet", "formation of platelet plugs", "platelet plugs cauwenberghs", "plugs cauwenberghs et", "cauwenberghs et al. 2000", "al. 2000 jilma", "2000 jilma stohlawetz", "jilma stohlawetz et al.", "stohlawetz et al. 2003", "al. 2003 debili", "2003 debili et", "debili et al. 1990", "et al. 1990 .", "al. 1990 . thbs1", "1990 . thbs1 homotrimers", ". thbs1 homotrimers contribute", "thbs1 homotrimers contribute to", "homotrimers contribute to stabilization", "contribute to stabilization of", "to stabilization of the", "stabilization of the platelet", "of the platelet aggregate", "platelet aggregate bonnefoy", "aggregate bonnefoy and", "bonnefoy and hoylaerts 2008", "and hoylaerts 2008 .", "hoylaerts 2008 . mir27a", "2008 . mir27a is", ". mir27a is a", "mir27a is a negative", "is a negative regulator", "a negative regulator of", "negative regulator of runx1", "regulator of runx1 mrna", "of runx1 mrna translation", "runx1 mrna translation and", "mrna translation and may", "translation and may be", "and may be involved", "may be involved in", "be involved in erythroid/megakaryocytic", "involved in erythroid/megakaryocytic lineage", "in erythroid/megakaryocytic lineage determination", "lineage determination ben", "determination ben ami", "ben ami et al.", "ami et al. 2009", "et al. 2009 .
the", "al. 2009 .
the runx1:cbfb", "2009 .
the runx1:cbfb complex", ".
the runx1:cbfb complex stimulates", "runx1:cbfb complex stimulates transcription", "complex stimulates transcription of", "stimulates transcription of the", "transcription of the pf4", "of the pf4 gene", "pf4 gene encoding", "gene encoding a", "encoding a component of", "a component of platelet", "component of platelet alpha", "of platelet alpha granules", "alpha granules aneja", "granules aneja et", "aneja et al. 2011", "2011 the", "nr4a3 gene associated", "gene associated with", "associated with the familial", "with the familial platelet", "the familial platelet disorder", "platelet disorder fpd", "fpd bluteau", "bluteau et al. 2011", "prkcq gene associated", "associated with inherited thrombocytopenia", "inherited thrombocytopenia jalagadugula", "thrombocytopenia jalagadugula et", "jalagadugula et al. 2011", "myl9 gene involved", "gene involved in", "in thrombopoiesis jalagadugula", "thrombopoiesis jalagadugula et", "jalagadugula et al. 2010", "2010 and", "and the nfe2 gene", "nfe2 gene a", "gene a regulator", "a regulator of erythroid", "regulator of erythroid and", "of erythroid and megakaryocytic", "erythroid and megakaryocytic maturation", "and megakaryocytic maturation and", "megakaryocytic maturation and differentiation", "and differentiation wang", "differentiation wang et", "wang et al. 2010", "et al. 2010 .", "human hematopoietic progenitors runx1", "hematopoietic progenitors runx1 and", "progenitors runx1 and its", "runx1 and its partner cbfb", "and its partner cbfb are", "its partner cbfb are up", "partner cbfb are up regulated", "cbfb are up regulated at", "are up regulated at the", "up regulated at the onset", "regulated at the onset of", "at the onset of megakaryocytic", "the onset of megakaryocytic differentiation", "onset of megakaryocytic differentiation and", "of megakaryocytic differentiation and down", "megakaryocytic differentiation and down regulated", "differentiation and down regulated at", "and down regulated at the", "down regulated at the onset", "at the onset of erythroid", "the onset of erythroid differentiation.", "onset of erythroid differentiation. the", "of erythroid differentiation. the complex", "erythroid differentiation. the complex of", "differentiation. the complex of runx1", "the complex of runx1 and", "complex of runx1 and cbfb", "of runx1 and cbfb cooperates", "runx1 and cbfb cooperates with", "and cbfb cooperates with the", "cbfb cooperates with the transcription", "cooperates with the transcription factor", "with the transcription factor gata1", "the transcription factor gata1 in", "transcription factor gata1 in the", "factor gata1 in the transactivation", "gata1 in the transactivation of", "in the transactivation of megakaryocyte", "the transactivation of megakaryocyte specific", "transactivation of megakaryocyte specific genes.", "of megakaryocyte specific genes. in", "megakaryocyte specific genes. in addition", "genes. in addition runx1", "in addition runx1 and", "addition runx1 and gata1", "runx1 and gata1 physically interact", "gata1 physically interact elagib", "physically interact elagib et", "interact elagib et al.", "al. 2003 and", "2003 and this", "and this interaction involves the", "this interaction involves the zinc", "interaction involves the zinc finger", "involves the zinc finger domain", "the zinc finger domain of", "zinc finger domain of gata1", "domain of gata1 xu", "of gata1 xu et", "gata1 xu et al.", "xu et al. 2006 .", "et al. 2006 . other", "al. 2006 . other components", "2006 . other components of", ". other components of the", "other components of the runx1:cbfb", "components of the runx1:cbfb activating", "of the runx1:cbfb activating complex", "the runx1:cbfb activating complex at", "runx1:cbfb activating complex at megakaryocytic", "activating complex at megakaryocytic promoters", "complex at megakaryocytic promoters are", "at megakaryocytic promoters are gata1", "megakaryocytic promoters are gata1 heterodimerization", "promoters are gata1 heterodimerization partner", "gata1 heterodimerization partner zfpm1", "partner zfpm1 fog1", "fog1 histone acetyltransferases", "histone acetyltransferases ep300 p300", "ep300 p300 and", "pcaf the wdr5", "the wdr5 containing histone methyltransferase", "wdr5 containing histone methyltransferase mll", "containing histone methyltransferase mll complex", "histone methyltransferase mll complex and", "methyltransferase mll complex and the", "mll complex and the arginine", "complex and the arginine methyltransferase", "and the arginine methyltransferase prmt1", "arginine methyltransferase prmt1 herglotz", "methyltransferase prmt1 herglotz et", "prmt1 herglotz et al.", "herglotz et al. 2013 .", "et al. 2013 . in", "al. 2013 . in the", "2013 . in the absence", ". in the absence of", "in the absence of prmt1", "absence of prmt1 the", "of prmt1 the transcriptional", "prmt1 the transcriptional repressor", "the transcriptional repressor complex can", "transcriptional repressor complex can form", "repressor complex can form at", "complex can form at megakaryocytic", "can form at megakaryocytic promoters", "at megakaryocytic promoters as", "megakaryocytic promoters as runx1", "promoters as runx1 that", "as runx1 that is not", "runx1 that is not arginine", "that is not arginine methylated", "is not arginine methylated can", "not arginine methylated can bind", "arginine methylated can bind to", "methylated can bind to sin3a/sin3b", "can bind to sin3a/sin3b co", "bind to sin3a/sin3b co repressors", "sin3a/sin3b co repressors zhao", "co repressors zhao et", "repressors zhao et al.", "zhao et al. 2008 .", "et al. 2008 . besides", "al. 2008 . besides sin3a/sin3b", ". besides sin3a/sin3b the", "besides sin3a/sin3b the runx1:cbfb", "sin3a/sin3b the runx1:cbfb repressor", "the runx1:cbfb repressor complex at", "runx1:cbfb repressor complex at megakaryocytic", "repressor complex at megakaryocytic promoters", "complex at megakaryocytic promoters also", "at megakaryocytic promoters also includes", "megakaryocytic promoters also includes histone", "promoters also includes histone deacetylase", "also includes histone deacetylase hdac1", "includes histone deacetylase hdac1 and", "histone deacetylase hdac1 and histone", "deacetylase hdac1 and histone arginine", "hdac1 and histone arginine methyltransferase", "and histone arginine methyltransferase prmt6", "arginine methyltransferase prmt6 herglotz", "methyltransferase prmt6 herglotz et", "prmt6 herglotz et al.", "herglotz et al. 2013 .
megakaryocytic", "et al. 2013 .
megakaryocytic promoters", "al. 2013 .
megakaryocytic promoters regulated", "2013 .
megakaryocytic promoters regulated by", ".
megakaryocytic promoters regulated by the", "promoters regulated by the described", "regulated by the described runx1:cbfb", "by the described runx1:cbfb activating", "the described runx1:cbfb activating and", "described runx1:cbfb activating and repressing", "runx1:cbfb activating and repressing complexes", "activating and repressing complexes include", "and repressing complexes include itga2b", "complexes include itga2b gp1ba", "itga2b gp1ba thbs1", "gp1ba thbs1 and mir27a", "thbs1 and mir27a herglotz", "and mir27a herglotz et", "mir27a herglotz et al.", "et al. 2013 . itga2b", "al. 2013 . itga2b is", "2013 . itga2b is only", ". itga2b is only expressed", "itga2b is only expressed in", "is only expressed in maturing", "only expressed in maturing megakaryocytes", "expressed in maturing megakaryocytes and", "in maturing megakaryocytes and platelets", "maturing megakaryocytes and platelets and", "megakaryocytes and platelets and is", "and platelets and is involved", "platelets and is involved in", "and is involved in platelet", "is involved in platelet aggregation", "in platelet aggregation block", "platelet aggregation block and", "aggregation block and poncz", "block and poncz 1995 .", "and poncz 1995 . gp1ba", "poncz 1995 . gp1ba is", "1995 . gp1ba is expressed", ". gp1ba is expressed at", "gp1ba is expressed at the", "is expressed at the cell", "expressed at the cell surface", "at the cell surface membrane", "the cell surface membrane of", "cell surface membrane of maturing", "surface membrane of maturing megakaryocytes", "membrane of maturing megakaryocytes and", "of maturing megakaryocytes and platelets", "megakaryocytes and platelets and participates", "and platelets and participates in", "platelets and participates in formation", "and participates in formation of", "participates in formation of platelet", "in formation of platelet plugs", "of platelet plugs cauwenberghs", "platelet plugs cauwenberghs et", "plugs cauwenberghs et al.", "et al. 2000 jilma", "al. 2000 jilma stohlawetz", "2000 jilma stohlawetz et", "jilma stohlawetz et al. 2003", "et al. 2003 debili", "al. 2003 debili et", "2003 debili et al.", "debili et al. 1990 .", "et al. 1990 . thbs1", "al. 1990 . thbs1 homotrimers", "1990 . thbs1 homotrimers contribute", ". thbs1 homotrimers contribute to", "thbs1 homotrimers contribute to stabilization", "homotrimers contribute to stabilization of", "contribute to stabilization of the", "to stabilization of the platelet", "stabilization of the platelet aggregate", "the platelet aggregate bonnefoy", "platelet aggregate bonnefoy and", "aggregate bonnefoy and hoylaerts", "bonnefoy and hoylaerts 2008 .", "and hoylaerts 2008 . mir27a", "hoylaerts 2008 . mir27a is", "2008 . mir27a is a", ". mir27a is a negative", "mir27a is a negative regulator", "is a negative regulator of", "a negative regulator of runx1", "negative regulator of runx1 mrna", "regulator of runx1 mrna translation", "of runx1 mrna translation and", "runx1 mrna translation and may", "mrna translation and may be", "translation and may be involved", "and may be involved in", "may be involved in erythroid/megakaryocytic", "be involved in erythroid/megakaryocytic lineage", "involved in erythroid/megakaryocytic lineage determination", "erythroid/megakaryocytic lineage determination ben", "lineage determination ben ami", "determination ben ami et", "ben ami et al. 2009", "ami et al. 2009 .
the", "et al. 2009 .
the runx1:cbfb", "al. 2009 .
the runx1:cbfb complex", "2009 .
the runx1:cbfb complex stimulates", ".
the runx1:cbfb complex stimulates transcription", "runx1:cbfb complex stimulates transcription of", "complex stimulates transcription of the", "stimulates transcription of the pf4", "transcription of the pf4 gene", "the pf4 gene encoding", "pf4 gene encoding a", "gene encoding a component", "encoding a component of platelet", "a component of platelet alpha", "component of platelet alpha granules", "platelet alpha granules aneja", "alpha granules aneja et", "granules aneja et al.", "al. 2011 the", "2011 the nr4a3", "the nr4a3 gene associated", "nr4a3 gene associated with", "gene associated with the", "associated with the familial platelet", "with the familial platelet disorder", "familial platelet disorder fpd", "fpd bluteau et", "2011 the prkcq", "the prkcq gene associated", "prkcq gene associated with", "gene associated with inherited", "with inherited thrombocytopenia jalagadugula", "inherited thrombocytopenia jalagadugula et", "thrombocytopenia jalagadugula et al.", "2011 the myl9", "the myl9 gene involved", "myl9 gene involved in", "gene involved in thrombopoiesis", "involved in thrombopoiesis jalagadugula", "in thrombopoiesis jalagadugula et", "thrombopoiesis jalagadugula et al.", "al. 2010 and", "2010 and the", "the nfe2 gene a", "nfe2 gene a regulator", "gene a regulator of", "a regulator of erythroid and", "regulator of erythroid and megakaryocytic", "of erythroid and megakaryocytic maturation", "erythroid and megakaryocytic maturation and", "and megakaryocytic maturation and differentiation", "maturation and differentiation wang", "and differentiation wang et", "differentiation wang et al.", "wang et al. 2010 ." ] }, { "record_id": "GLY_000594_1_633", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8937144", "r hsa", "hsa 8937144", "r hsa 8937144" ] }, { "record_id": "GLY_000594_1_633", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "aryl hydrocarbon", "hydrocarbon receptor", "receptor signalling", "aryl hydrocarbon receptor", "hydrocarbon receptor signalling", "aryl hydrocarbon receptor signalling", "the aryl", "is a", "a ligand", "ligand activated", "activated transcription", "transcription factor", "factor that", "that belongs", "belongs to", "to the", "the basic", "basic helix", "helix loop", "loop helix/per", "helix/per arnt", "arnt sim", "sim family", "family of", "of dna", "dna binding", "binding proteins", "proteins and", "and controls", "controls the", "the expression", "expression of", "of a", "a diverse", "diverse set", "set of", "of genes.", "genes. two", "two major", "major types", "types of", "of environmental", "environmental compounds", "compounds can", "can activate", "activate ahr", "ahr signaling:", "signaling: halogenated", "halogenated aromatic", "aromatic hydrocarbons", "hydrocarbons such", "such as", "as 2", "2 3", "3 7", "7 8", "8 tetrachlorodibenzo", "tetrachlorodibenzo p", "p dioxin", "and polycyclic", "polycyclic aromatic", "as benzo", "benzo a", "a pyrene.", "pyrene. unliganded", "unliganded ahr", "ahr forms", "forms a", "a complex", "complex in", "in the", "the cytosol", "cytosol with", "with two", "two copies", "copies of", "of 90kd", "90kd heat", "heat shock", "shock protein", "one x", "x associated", "associated protein", "and one", "one p23", "p23 molecular", "molecular chaperone", "chaperone protein", "ptges3 .", ". after", "after ligand", "ligand binding", "binding and", "and activation", "the ahr", "ahr complex", "complex translocates", "translocates to", "the nucleus", "disassociates from", "from the", "the chaperone", "chaperone subunits", "dimerises with", "with the", "receptor nuclear", "nuclear translocator", "and transactivates", "transactivates target", "target genes", "genes via", "via binding", "binding to", "to xenobiotic", "xenobiotic response", "response elements", "in their", "their promoter", "promoter regions.", "regions. ahr", "ahr targets", "targets genes", "genes of", "of phase", "phase i", "i and", "and phase", "phase ii", "ii metabolism", "as cytochrome", "cytochrome p450", "p450 1a1", "cytochorme p450", "p450 1b1", "nad p", "p h:quinone", "h:quinone oxidoreductase", "oxidoreductase i", "and aldehyde", "aldehyde dehydrogenase", "dehydrogenase 3", "alhd3a1 .", ". this", "this is", "is thought", "thought to", "to be", "be an", "an organism's", "organism's response", "response to", "to foreign", "foreign chemical", "chemical exposure", "exposure and", "and normally", "foreign chemicals", "chemicals are", "are made", "made less", "less reactive", "reactive by", "by the", "the induction", "induction and", "and therefore", "therefore increased", "increased activity", "activity of", "of these", "these enzymes", "beischlag et", "et al.", "al. 2008", "2008 .

ahr", ".

ahr itself", "itself is", "is regulated", "regulated by", "receptor repressor", "aka bhlhe77", "an evolutionarily", "evolutionarily conserved", "conserved bhlh", "bhlh pas", "pas protein", "protein that", "that inhibits", "inhibits both", "both xenobiotic", "xenobiotic induced", "induced and", "and constitutively", "constitutively active", "active ahr", "ahr transcriptional", "transcriptional activity", "activity in", "in many", "many species.", "species. ahrr", "resides predominantly", "predominantly in", "the nuclear", "nuclear compartment", "compartment where", "where it", "it competes", "competes with", "with ahr", "ahr for", "for binding", "to arnt.", "arnt. as", "as a", "a result", "there is", "is competition", "competition between", "between ahr:arnt", "ahr:arnt and", "and ahrr:arnt", "ahrr:arnt complexes", "complexes for", "to xres", "xres in", "in target", "genes and", "and ahrr", "ahrr can", "can repress", "repress the", "the transcription", "transcription activity", "of ahr", "hahn et", "al. 2009", "haarmann stemmann", "stemmann &", "& abel", "abel 2006", "2006 .", "the aryl hydrocarbon", "receptor ahr", "ahr is", "is a ligand", "a ligand activated", "ligand activated transcription", "activated transcription factor", "transcription factor that", "factor that belongs", "that belongs to", "belongs to the", "to the basic", "the basic helix", "basic helix loop", "helix loop helix/per", "loop helix/per arnt", "helix/per arnt sim", "arnt sim family", "sim family of", "family of dna", "of dna binding", "dna binding proteins", "binding proteins and", "proteins and controls", "and controls the", "controls the expression", "the expression of", "expression of a", "of a diverse", "a diverse set", "diverse set of", "set of genes.", "of genes. two", "genes. two major", "two major types", "major types of", "types of environmental", "of environmental compounds", "environmental compounds can", "compounds can activate", "can activate ahr", "activate ahr signaling:", "ahr signaling: halogenated", "signaling: halogenated aromatic", "halogenated aromatic hydrocarbons", "aromatic hydrocarbons such", "hydrocarbons such as", "such as 2", "as 2 3", "2 3 7", "3 7 8", "7 8 tetrachlorodibenzo", "8 tetrachlorodibenzo p", "tetrachlorodibenzo p dioxin", "dioxin tcdd", "tcdd and", "and polycyclic aromatic", "polycyclic aromatic hydrocarbons", "hydrocarbons pah", "pah such", "such as benzo", "as benzo a", "benzo a pyrene.", "a pyrene. unliganded", "pyrene. unliganded ahr", "unliganded ahr forms", "ahr forms a", "forms a complex", "a complex in", "complex in the", "in the cytosol", "the cytosol with", "cytosol with two", "with two copies", "two copies of", "copies of 90kd", "of 90kd heat", "90kd heat shock", "heat shock protein", "protein hsp90ab1", "one x associated", "x associated protein", "protein aip", "and one p23", "one p23 molecular", "p23 molecular chaperone", "molecular chaperone protein", "protein ptges3", "ptges3 . after", ". after ligand", "after ligand binding", "ligand binding and", "binding and activation", "activation the", "the ahr complex", "ahr complex translocates", "complex translocates to", "translocates to the", "to the nucleus", "nucleus disassociates", "disassociates from the", "from the chaperone", "the chaperone subunits", "subunits dimerises", "dimerises with the", "with the aryl", "hydrocarbon receptor nuclear", "receptor nuclear translocator", "translocator arnt", "arnt and", "and transactivates target", "transactivates target genes", "target genes via", "genes via binding", "via binding to", "binding to xenobiotic", "to xenobiotic response", "xenobiotic response elements", "elements xres", "in their promoter", "their promoter regions.", "promoter regions. ahr", "regions. ahr targets", "ahr targets genes", "targets genes of", "genes of phase", "of phase i", "phase i and", "i and phase", "and phase ii", "phase ii metabolism", "metabolism such", "such as cytochrome", "as cytochrome p450", "cytochrome p450 1a1", "1a1 cyp1a1", "cytochorme p450 1b1", "1b1 cyp1b1", "nad p h:quinone", "p h:quinone oxidoreductase", "h:quinone oxidoreductase i", "i nqo1", "nqo1 and", "and aldehyde dehydrogenase", "aldehyde dehydrogenase 3", "3 alhd3a1", "alhd3a1 . this", ". this is", "this is thought", "is thought to", "thought to be", "to be an", "be an organism's", "an organism's response", "organism's response to", "response to foreign", "to foreign chemical", "foreign chemical exposure", "chemical exposure and", "exposure and normally", "normally foreign", "foreign chemicals are", "chemicals are made", "are made less", "made less reactive", "less reactive by", "reactive by the", "by the induction", "the induction and", "induction and therefore", "and therefore increased", "therefore increased activity", "increased activity of", "activity of these", "of these enzymes", "enzymes beischlag", "beischlag et al.", "et al. 2008", "al. 2008 .

ahr", "2008 .

ahr itself", ".

ahr itself is", "itself is regulated", "is regulated by", "regulated by the", "by the aryl", "hydrocarbon receptor repressor", "repressor ahrr", "ahrr aka", "bhlhe77 kiaa1234", "an evolutionarily conserved", "evolutionarily conserved bhlh", "conserved bhlh pas", "bhlh pas protein", "pas protein that", "protein that inhibits", "that inhibits both", "inhibits both xenobiotic", "both xenobiotic induced", "xenobiotic induced and", "induced and constitutively", "and constitutively active", "constitutively active ahr", "active ahr transcriptional", "ahr transcriptional activity", "transcriptional activity in", "activity in many", "in many species.", "many species. ahrr", "ahrr resides", "resides predominantly in", "predominantly in the", "in the nuclear", "the nuclear compartment", "nuclear compartment where", "compartment where it", "where it competes", "it competes with", "competes with ahr", "with ahr for", "ahr for binding", "for binding to", "binding to arnt.", "to arnt. as", "arnt. as a", "as a result", "result there", "there is competition", "is competition between", "competition between ahr:arnt", "between ahr:arnt and", "ahr:arnt and ahrr:arnt", "and ahrr:arnt complexes", "ahrr:arnt complexes for", "complexes for binding", "binding to xres", "to xres in", "xres in target", "in target genes", "target genes and", "genes and ahrr", "and ahrr can", "ahrr can repress", "can repress the", "repress the transcription", "the transcription activity", "transcription activity of", "activity of ahr", "ahr hahn", "hahn et al.", "et al. 2009", "2009 haarmann", "haarmann stemmann &", "stemmann & abel", "& abel 2006", "abel 2006 .", "the aryl hydrocarbon receptor", "hydrocarbon receptor ahr", "ahr is a", "is a ligand activated", "a ligand activated transcription", "ligand activated transcription factor", "activated transcription factor that", "transcription factor that belongs", "factor that belongs to", "that belongs to the", "belongs to the basic", "to the basic helix", "the basic helix loop", "basic helix loop helix/per", "helix loop helix/per arnt", "loop helix/per arnt sim", "helix/per arnt sim family", "arnt sim family of", "sim family of dna", "family of dna binding", "of dna binding proteins", "dna binding proteins and", "binding proteins and controls", "proteins and controls the", "and controls the expression", "controls the expression of", "the expression of a", "expression of a diverse", "of a diverse set", "a diverse set of", "diverse set of genes.", "set of genes. two", "of genes. two major", "genes. two major types", "two major types of", "major types of environmental", "types of environmental compounds", "of environmental compounds can", "environmental compounds can activate", "compounds can activate ahr", "can activate ahr signaling:", "activate ahr signaling: halogenated", "ahr signaling: halogenated aromatic", "signaling: halogenated aromatic hydrocarbons", "halogenated aromatic hydrocarbons such", "aromatic hydrocarbons such as", "hydrocarbons such as 2", "such as 2 3", "as 2 3 7", "2 3 7 8", "3 7 8 tetrachlorodibenzo", "7 8 tetrachlorodibenzo p", "8 tetrachlorodibenzo p dioxin", "p dioxin tcdd", "tcdd and polycyclic", "and polycyclic aromatic hydrocarbons", "aromatic hydrocarbons pah", "pah such as", "such as benzo a", "as benzo a pyrene.", "benzo a pyrene. unliganded", "a pyrene. unliganded ahr", "pyrene. unliganded ahr forms", "unliganded ahr forms a", "ahr forms a complex", "forms a complex in", "a complex in the", "complex in the cytosol", "in the cytosol with", "the cytosol with two", "cytosol with two copies", "with two copies of", "two copies of 90kd", "copies of 90kd heat", "of 90kd heat shock", "90kd heat shock protein", "shock protein hsp90ab1", "hsp90ab1 one", "one x associated protein", "associated protein aip", "aip and", "and one p23 molecular", "one p23 molecular chaperone", "p23 molecular chaperone protein", "chaperone protein ptges3", "protein ptges3 .", "ptges3 . after ligand", ". after ligand binding", "after ligand binding and", "ligand binding and activation", "and activation the", "activation the ahr", "the ahr complex translocates", "ahr complex translocates to", "complex translocates to the", "translocates to the nucleus", "the nucleus disassociates", "nucleus disassociates from", "disassociates from the chaperone", "from the chaperone subunits", "chaperone subunits dimerises", "subunits dimerises with", "dimerises with the aryl", "with the aryl hydrocarbon", "aryl hydrocarbon receptor nuclear", "hydrocarbon receptor nuclear translocator", "nuclear translocator arnt", "arnt and transactivates", "and transactivates target genes", "transactivates target genes via", "target genes via binding", "genes via binding to", "via binding to xenobiotic", "binding to xenobiotic response", "to xenobiotic response elements", "response elements xres", "xres in their", "in their promoter regions.", "their promoter regions. ahr", "promoter regions. ahr targets", "regions. ahr targets genes", "ahr targets genes of", "targets genes of phase", "genes of phase i", "of phase i and", "phase i and phase", "i and phase ii", "and phase ii metabolism", "ii metabolism such", "metabolism such as", "such as cytochrome p450", "as cytochrome p450 1a1", "p450 1a1 cyp1a1", "cyp1a1 cytochorme", "p450 1b1 cyp1b1", "cyp1b1 nad", "nad p h:quinone oxidoreductase", "p h:quinone oxidoreductase i", "oxidoreductase i nqo1", "nqo1 and aldehyde", "and aldehyde dehydrogenase 3", "dehydrogenase 3 alhd3a1", "3 alhd3a1 .", "alhd3a1 . this is", ". this is thought", "this is thought to", "is thought to be", "thought to be an", "to be an organism's", "be an organism's response", "an organism's response to", "organism's response to foreign", "response to foreign chemical", "to foreign chemical exposure", "foreign chemical exposure and", "chemical exposure and normally", "and normally foreign", "normally foreign chemicals", "foreign chemicals are made", "chemicals are made less", "are made less reactive", "made less reactive by", "less reactive by the", "reactive by the induction", "by the induction and", "the induction and therefore", "induction and therefore increased", "and therefore increased activity", "therefore increased activity of", "increased activity of these", "activity of these enzymes", "these enzymes beischlag", "enzymes beischlag et", "beischlag et al. 2008", "et al. 2008 .

ahr", "al. 2008 .

ahr itself", "2008 .

ahr itself is", ".

ahr itself is regulated", "itself is regulated by", "is regulated by the", "regulated by the aryl", "by the aryl hydrocarbon", "aryl hydrocarbon receptor repressor", "receptor repressor ahrr", "ahrr aka bhlhe77", "aka bhlhe77 kiaa1234", "kiaa1234 an", "an evolutionarily conserved bhlh", "evolutionarily conserved bhlh pas", "conserved bhlh pas protein", "bhlh pas protein that", "pas protein that inhibits", "protein that inhibits both", "that inhibits both xenobiotic", "inhibits both xenobiotic induced", "both xenobiotic induced and", "xenobiotic induced and constitutively", "induced and constitutively active", "and constitutively active ahr", "constitutively active ahr transcriptional", "active ahr transcriptional activity", "ahr transcriptional activity in", "transcriptional activity in many", "activity in many species.", "in many species. ahrr", "species. ahrr resides", "ahrr resides predominantly", "resides predominantly in the", "predominantly in the nuclear", "in the nuclear compartment", "the nuclear compartment where", "nuclear compartment where it", "compartment where it competes", "where it competes with", "it competes with ahr", "competes with ahr for", "with ahr for binding", "ahr for binding to", "for binding to arnt.", "binding to arnt. as", "to arnt. as a", "arnt. as a result", "a result there", "result there is", "there is competition between", "is competition between ahr:arnt", "competition between ahr:arnt and", "between ahr:arnt and ahrr:arnt", "ahr:arnt and ahrr:arnt complexes", "and ahrr:arnt complexes for", "ahrr:arnt complexes for binding", "complexes for binding to", "for binding to xres", "binding to xres in", "to xres in target", "xres in target genes", "in target genes and", "target genes and ahrr", "genes and ahrr can", "and ahrr can repress", "ahrr can repress the", "can repress the transcription", "repress the transcription activity", "the transcription activity of", "transcription activity of ahr", "of ahr hahn", "ahr hahn et", "hahn et al. 2009", "al. 2009 haarmann", "2009 haarmann stemmann", "haarmann stemmann & abel", "stemmann & abel 2006", "& abel 2006 .", "aryl hydrocarbon receptor ahr", "receptor ahr is", "ahr is a ligand", "is a ligand activated transcription", "a ligand activated transcription factor", "ligand activated transcription factor that", "activated transcription factor that belongs", "transcription factor that belongs to", "factor that belongs to the", "that belongs to the basic", "belongs to the basic helix", "to the basic helix loop", "the basic helix loop helix/per", "basic helix loop helix/per arnt", "helix loop helix/per arnt sim", "loop helix/per arnt sim family", "helix/per arnt sim family of", "arnt sim family of dna", "sim family of dna binding", "family of dna binding proteins", "of dna binding proteins and", "dna binding proteins and controls", "binding proteins and controls the", "proteins and controls the expression", "and controls the expression of", "controls the expression of a", "the expression of a diverse", "expression of a diverse set", "of a diverse set of", "a diverse set of genes.", "diverse set of genes. two", "set of genes. two major", "of genes. two major types", "genes. two major types of", "two major types of environmental", "major types of environmental compounds", "types of environmental compounds can", "of environmental compounds can activate", "environmental compounds can activate ahr", "compounds can activate ahr signaling:", "can activate ahr signaling: halogenated", "activate ahr signaling: halogenated aromatic", "ahr signaling: halogenated aromatic hydrocarbons", "signaling: halogenated aromatic hydrocarbons such", "halogenated aromatic hydrocarbons such as", "aromatic hydrocarbons such as 2", "hydrocarbons such as 2 3", "such as 2 3 7", "as 2 3 7 8", "2 3 7 8 tetrachlorodibenzo", "3 7 8 tetrachlorodibenzo p", "7 8 tetrachlorodibenzo p dioxin", "tetrachlorodibenzo p dioxin tcdd", "dioxin tcdd and", "tcdd and polycyclic aromatic", "polycyclic aromatic hydrocarbons pah", "hydrocarbons pah such", "pah such as benzo", "such as benzo a pyrene.", "as benzo a pyrene. unliganded", "benzo a pyrene. unliganded ahr", "a pyrene. unliganded ahr forms", "pyrene. unliganded ahr forms a", "unliganded ahr forms a complex", "ahr forms a complex in", "forms a complex in the", "a complex in the cytosol", "complex in the cytosol with", "in the cytosol with two", "the cytosol with two copies", "cytosol with two copies of", "with two copies of 90kd", "two copies of 90kd heat", "copies of 90kd heat shock", "of 90kd heat shock protein", "heat shock protein hsp90ab1", "hsp90ab1 one x", "x associated protein aip", "aip and one", "and one p23 molecular chaperone", "one p23 molecular chaperone protein", "molecular chaperone protein ptges3", "chaperone protein ptges3 .", "protein ptges3 . after", "ptges3 . after ligand binding", ". after ligand binding and", "after ligand binding and activation", "binding and activation the", "and activation the ahr", "activation the ahr complex", "the ahr complex translocates to", "ahr complex translocates to the", "complex translocates to the nucleus", "to the nucleus disassociates", "the nucleus disassociates from", "nucleus disassociates from the", "disassociates from the chaperone subunits", "the chaperone subunits dimerises", "chaperone subunits dimerises with", "subunits dimerises with the", "dimerises with the aryl hydrocarbon", "with the aryl hydrocarbon receptor", "the aryl hydrocarbon receptor nuclear", "aryl hydrocarbon receptor nuclear translocator", "receptor nuclear translocator arnt", "translocator arnt and", "arnt and transactivates target", "and transactivates target genes via", "transactivates target genes via binding", "target genes via binding to", "genes via binding to xenobiotic", "via binding to xenobiotic response", "binding to xenobiotic response elements", "xenobiotic response elements xres", "elements xres in", "xres in their promoter", "in their promoter regions. ahr", "their promoter regions. ahr targets", "promoter regions. ahr targets genes", "regions. ahr targets genes of", "ahr targets genes of phase", "targets genes of phase i", "genes of phase i and", "of phase i and phase", "phase i and phase ii", "i and phase ii metabolism", "phase ii metabolism such", "ii metabolism such as", "metabolism such as cytochrome", "such as cytochrome p450 1a1", "cytochrome p450 1a1 cyp1a1", "cyp1a1 cytochorme p450", "cytochorme p450 1b1 cyp1b1", "cyp1b1 nad p", "nad p h:quinone oxidoreductase i", "h:quinone oxidoreductase i nqo1", "i nqo1 and", "nqo1 and aldehyde dehydrogenase", "aldehyde dehydrogenase 3 alhd3a1", "dehydrogenase 3 alhd3a1 .", "3 alhd3a1 . this", "alhd3a1 . this is thought", ". this is thought to", "this is thought to be", "is thought to be an", "thought to be an organism's", "to be an organism's response", "be an organism's response to", "an organism's response to foreign", "organism's response to foreign chemical", "response to foreign chemical exposure", "to foreign chemical exposure and", "foreign chemical exposure and normally", "exposure and normally foreign", "and normally foreign chemicals", "normally foreign chemicals are", "foreign chemicals are made less", "chemicals are made less reactive", "are made less reactive by", "made less reactive by the", "less reactive by the induction", "reactive by the induction and", "by the induction and therefore", "the induction and therefore increased", "induction and therefore increased activity", "and therefore increased activity of", "therefore increased activity of these", "increased activity of these enzymes", "of these enzymes beischlag", "these enzymes beischlag et", "enzymes beischlag et al.", "beischlag et al. 2008 .

ahr", "et al. 2008 .

ahr itself", "al. 2008 .

ahr itself is", "2008 .

ahr itself is regulated", ".

ahr itself is regulated by", "itself is regulated by the", "is regulated by the aryl", "regulated by the aryl hydrocarbon", "by the aryl hydrocarbon receptor", "the aryl hydrocarbon receptor repressor", "hydrocarbon receptor repressor ahrr", "repressor ahrr aka", "kiaa1234 an evolutionarily", "an evolutionarily conserved bhlh pas", "evolutionarily conserved bhlh pas protein", "conserved bhlh pas protein that", "bhlh pas protein that inhibits", "pas protein that inhibits both", "protein that inhibits both xenobiotic", "that inhibits both xenobiotic induced", "inhibits both xenobiotic induced and", "both xenobiotic induced and constitutively", "xenobiotic induced and constitutively active", "induced and constitutively active ahr", "and constitutively active ahr transcriptional", "constitutively active ahr transcriptional activity", "active ahr transcriptional activity in", "ahr transcriptional activity in many", "transcriptional activity in many species.", "activity in many species. ahrr", "many species. ahrr resides", "species. ahrr resides predominantly", "ahrr resides predominantly in", "resides predominantly in the nuclear", "predominantly in the nuclear compartment", "in the nuclear compartment where", "the nuclear compartment where it", "nuclear compartment where it competes", "compartment where it competes with", "where it competes with ahr", "it competes with ahr for", "competes with ahr for binding", "with ahr for binding to", "ahr for binding to arnt.", "for binding to arnt. as", "binding to arnt. as a", "to arnt. as a result", "as a result there", "a result there is", "result there is competition", "there is competition between ahr:arnt", "is competition between ahr:arnt and", "competition between ahr:arnt and ahrr:arnt", "between ahr:arnt and ahrr:arnt complexes", "ahr:arnt and ahrr:arnt complexes for", "and ahrr:arnt complexes for binding", "ahrr:arnt complexes for binding to", "complexes for binding to xres", "for binding to xres in", "binding to xres in target", "to xres in target genes", "xres in target genes and", "in target genes and ahrr", "target genes and ahrr can", "genes and ahrr can repress", "and ahrr can repress the", "ahrr can repress the transcription", "can repress the transcription activity", "repress the transcription activity of", "the transcription activity of ahr", "activity of ahr hahn", "of ahr hahn et", "ahr hahn et al.", "et al. 2009 haarmann", "al. 2009 haarmann stemmann", "2009 haarmann stemmann &", "haarmann stemmann & abel 2006", "stemmann & abel 2006 ." ] }, { "record_id": "GLY_000594_1_634", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8939236", "r hsa", "hsa 8939236", "r hsa 8939236" ] }, { "record_id": "GLY_000594_1_634", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "runx1 regulates", "regulates transcription", "transcription of", "of genes", "genes involved", "involved in", "in differentiation", "differentiation of", "of hscs", "runx1 regulates transcription", "regulates transcription of", "transcription of genes", "of genes involved", "genes involved in", "involved in differentiation", "in differentiation of", "differentiation of hscs", "runx1 regulates transcription of", "regulates transcription of genes", "transcription of genes involved", "of genes involved in", "genes involved in differentiation", "involved in differentiation of", "in differentiation of hscs", "runx1 regulates transcription of genes", "regulates transcription of genes involved", "transcription of genes involved in", "of genes involved in differentiation", "genes involved in differentiation of", "involved in differentiation of hscs", "the runx1:cbfb", "runx1:cbfb complex", "complex regulates", "of the", "the spi1", "of hematopoietic", "hematopoietic stem", "stem cells", "hscs .", ". runx1", "runx1 recruits", "recruits histone", "histone methyltransferase", "methyltransferase kmt2a", "to the", "spi1 gene", "gene locus", "leading to", "to generation", "generation of", "the activating", "activating h3k4me3", "h3k4me3 mark", "mark on", "on nucleosomes", "nucleosomes associated", "associated with", "with the", "spi1 promoter", "promoter and", "and the", "the upstream", "upstream regulatory", "regulatory element", "huang et", "et al.", "al. 2011", "2011 .", ". spi1", "spi1 transactivation", "transactivation represses", "represses self", "self renewal", "renewal and", "and proliferation", "proliferation of", "fukuchi et", "al. 2008", "and is", "is needed", "needed for", "for commitment", "commitment of", "hscs to", "to specific", "specific hematopoietic", "hematopoietic lineages", "imperato et", "al. 2015", "2015 .
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activated", ".
activated estrogen", "estrogen receptor", "receptor alpha", "binds estrogen", "estrogen response", "response elements", "in the", "the p2", "promoter and", "and stimulates", "stimulates runx2", "runx2 transcription", "kammerer et", "et al.", "al. 2013", "2013 .", ". estrogen", "estrogen related", "related receptor", "binds eres", "eres or", "or estrogen", "related response", "promoter of", "of runx2.", "runx2. when", "when erra", "erra is", "is bound", "bound to", "to its", "its co", "co factor", "factor pparg1ca", "it stimulates", "runx2 transcription.", "transcription. when", "when bound", "factor pparg1cb", "erra represses", "represses runx2", "2013 .
twist1", "a basic", "basic helix", "helix loop", "loop helix", "transcription factor", "transcription by", "by binding", "binding to", "the e1", "e1 box", "box in", "yang et", "al. 2011", "2011 .", ". twist", "twist proteins", "proteins also", "also interact", "interact with", "with the", "the dna", "dna binding", "binding domain", "domain of", "runx2 to", "to modulate", "modulate its", "its activity", "activity during", "during skeletogenesis", "bialek et", "al. 2004", "2004 .", ". schnurri", "schnurri 3", "is another", "another protein", "protein that", "that interacts", "interacts with", "with runx2", "to decrease", "decrease its", "its availability", "availability in", "the nucleus", "nucleus and", "and therefore", "therefore its", "jones et", "al. 2006", "2006 .", ". in", "in contrast", "runx2 and", "and satb2", "satb2 interact", "interact to", "to enhance", "enhance the", "the expression", "expression of", "of osteoblast", "osteoblast specific", "specific genes", "dobreva et", ". formation", "formation of", "the heterodimer", "heterodimer with", "with cbfb", "cbf beta", "also enhances", "enhances the", "the transcriptional", "transcriptional activity", "activity of", "kundu et", "al. 2002", "yoshida et", "otto et", "2002 .
transcription", ".
transcription of", "runx2 from", "proximal promoter", "promoter is", "is inhibited", "inhibited by", "binding of", "the glucocorticoid", "glucocorticoid receptor", "activated by", "by dexamethasone", "to a", "a glucocorticoid", "receptor response", "response element", "which is", "is also", "also present", "present in", "the human", "human promoter", "zhang et", "al. 2012", "2012 .
nkx3", ".
nkx3 2", "required for", "for embryonic", "embryonic development", "development of", "the axial", "axial skeleton", "tribioli and", "and lufkin", "lufkin 1999", "binds the", "gene and", "and inhibits", "inhibits its", "its transcription", "lengner et", "al. 2005", "2005 .", ". runx2", "runx2 p1", "p1 transcription", "transcription is", "also autoinhibited", "autoinhibited by", "by runx2", "which binds", "binds to", "to runx2", "runx2 response", "elements in", "the p1", "drissi et", "al. 2000", "2000 .", "runx2 p2", "p2 to", "promoter autoactivates", "autoactivates transcription", "transcription of", "ducy et", "al. 1999", "1999 .", ". binding", "of a", "a homeodomain", "homeodomain transcription", "factor dlx5", "and possibly", "possibly dlx6", "promoter stimulates", "robledo et", "lee et", ". the", "the homeobox", "homeobox transcription", "factor msx2", "msx2 can", "can bind", "bind to", "to dlx5", "dlx5 sites", "sites in", "the promoter", "and inhibit", "inhibit transcription", "2005 .
translocation", ".
translocation of", "runx2 protein", "protein to", "nucleus is", "to non", "non activated", "activated stat1", "kim et", "al. 2003", "2003 .
several", ".
several e3", "e3 ubiquitin", "ubiquitin ligases", "ligases were", "were shown", "shown to", "to polyubiquitinate", "polyubiquitinate runx2", "targeting it", "it for", "for proteasome", "proteasome mediated", "mediated degradation:", "degradation: stub1", "li et", "al. 2008", "zhao et", "al. 2014", "and skp2", "thacker et", "al. 2016", "2016 .", "several transcription factors", "transcription factors have", "factors have been", "have been implicated", "been implicated in", "implicated in regulation", "in regulation of", "regulation of the", "of the runx2", "the runx2 gene", "runx2 gene transcription.", "gene transcription. similar", "transcription. similar to", "similar to the", "to the runx1", "the runx1 gene", "gene the", "runx2 gene expression", "gene expression can", "expression can be", "can be regulated", "be regulated from", "regulated from the", "from the proximal", "the proximal p2", "proximal p2 promoter", "p2 promoter or", "promoter or the", "or the distal", "the distal p1", "distal p1 promoter", "promoter reviewed", "reviewed in li", "in li and", "li and xiao", "and xiao 2007", "xiao 2007 .
activated", "2007 .
activated estrogen", ".
activated estrogen receptor", "estrogen receptor alpha", "alpha esr1", "esr1 binds", "binds estrogen response", "estrogen response elements", "elements eres", "eres in", "in the p2", "the p2 promoter", "p2 promoter and", "promoter and stimulates", "and stimulates runx2", "stimulates runx2 transcription", "transcription kammerer", "kammerer et al.", "et al. 2013", "al. 2013 .", "2013 . estrogen", ". estrogen related", "estrogen related receptor", "related receptor alpha", "alpha erra", "erra binds", "binds eres or", "eres or estrogen", "or estrogen related", "estrogen related response", "related response elements", "elements erres", "erres in", "p2 promoter of", "promoter of runx2.", "of runx2. when", "runx2. when erra", "when erra is", "erra is bound", "is bound to", "bound to its", "to its co", "its co factor", "co factor pparg1ca", "pparg1ca pgc1a", "it stimulates runx2", "stimulates runx2 transcription.", "runx2 transcription. when", "transcription. when bound", "when bound to", "co factor pparg1cb", "pparg1cb pgc1b", "erra represses runx2", "represses runx2 transcription", "al. 2013 .
twist1", ".
twist1 a", "a basic helix", "basic helix loop", "helix loop helix", "helix bhlh", "bhlh transcription", "factor stimulates", "runx2 transcription by", "transcription by binding", "by binding to", "binding to the", "to the e1", "the e1 box", "e1 box in", "box in the", "promoter yang", "yang yang", "yang et al.", "et al. 2011", "al. 2011 .", "2011 . twist", ". twist proteins", "twist proteins also", "proteins also interact", "also interact with", "interact with the", "with the dna", "the dna binding", "dna binding domain", "binding domain of", "domain of runx2", "of runx2 to", "runx2 to modulate", "to modulate its", "modulate its activity", "its activity during", "activity during skeletogenesis", "skeletogenesis bialek", "bialek et al.", "et al. 2004", "al. 2004 .", "2004 . schnurri", ". schnurri 3", "3 shn3", "shn3 is", "is another protein", "another protein that", "protein that interacts", "that interacts with", "interacts with runx2", "with runx2 to", "runx2 to decrease", "to decrease its", "decrease its availability", "its availability in", "availability in the", "in the nucleus", "the nucleus and", "nucleus and therefore", "and therefore its", "therefore its activity", "activity jones", "jones et al.", "et al. 2006", "al. 2006 .", "2006 . in", ". in contrast", "contrast runx2", "runx2 and satb2", "and satb2 interact", "satb2 interact to", "interact to enhance", "to enhance the", "enhance the expression", "the expression of", "expression of osteoblast", "of osteoblast specific", "osteoblast specific genes", "genes dobreva", "dobreva et al.", "2006 . formation", ". formation of", "formation of the", "of the heterodimer", "the heterodimer with", "heterodimer with cbfb", "cbfb cbf", "beta also", "also enhances the", "enhances the transcriptional", "the transcriptional activity", "transcriptional activity of", "activity of runx2", "runx2 kundu", "kundu et al.", "et al. 2002", "2002 yoshida", "yoshida et al.", "2002 otto", "otto et al.", "al. 2002 .
transcription", "2002 .
transcription of", ".
transcription of runx2", "of runx2 from", "runx2 from the", "the proximal promoter", "proximal promoter is", "promoter is inhibited", "is inhibited by", "inhibited by binding", "by binding of", "binding of the", "of the glucocorticoid", "the glucocorticoid receptor", "receptor nr3c1", "nr3c1 activated", "activated by dexamethasone", "dexamethasone dexa", "dexa to", "to a glucocorticoid", "a glucocorticoid receptor", "glucocorticoid receptor response", "receptor response element", "element gre", "which is also", "is also present", "also present in", "present in the", "in the human", "the human promoter", "promoter zhang", "zhang et al.", "et al. 2012", "al. 2012 .
nkx3", "2012 .
nkx3 2", "2 bapx1", "required for embryonic", "for embryonic development", "embryonic development of", "development of the", "of the axial", "the axial skeleton", "skeleton tribioli", "tribioli and lufkin", "and lufkin 1999", "binds the distal", "promoter of the", "runx2 gene and", "gene and inhibits", "and inhibits its", "inhibits its transcription", "transcription lengner", "lengner et al.", "et al. 2005", "al. 2005 .", "2005 . runx2", ". runx2 p1", "runx2 p1 transcription", "p1 transcription is", "transcription is also", "is also autoinhibited", "also autoinhibited by", "autoinhibited by runx2", "by runx2 p1", "p1 which", "which binds to", "binds to runx2", "to runx2 response", "runx2 response elements", "response elements in", "elements in the", "in the p1", "the p1 promoter", "p1 promoter of", "promoter of runx2", "runx2 drissi", "drissi et al.", "et al. 2000", "al. 2000 .", "2000 . in", "contrast binding", "binding of runx2", "of runx2 p2", "runx2 p2 to", "p2 to the", "to the proximal", "p2 promoter autoactivates", "promoter autoactivates transcription", "autoactivates transcription of", "transcription of runx2", "p2 ducy", "ducy et al.", "et al. 1999", "al. 1999 .", "1999 . binding", ". binding of", "binding of a", "of a homeodomain", "a homeodomain transcription", "homeodomain transcription factor", "transcription factor dlx5", "dlx5 and", "and possibly dlx6", "dlx6 to", "to the runx2", "the runx2 p1", "runx2 p1 promoter", "p1 promoter stimulates", "promoter stimulates runx2", "transcription robledo", "robledo et al.", "2002 lee", "lee et al.", "2005 . the", ". the homeobox", "the homeobox transcription", "homeobox transcription factor", "transcription factor msx2", "factor msx2 can", "msx2 can bind", "can bind to", "bind to dlx5", "to dlx5 sites", "dlx5 sites in", "sites in the", "in the promoter", "the promoter of", "of runx2 and", "runx2 and inhibit", "and inhibit transcription", "inhibit transcription of", "of runx2 p1", "p1 lee", "al. 2005 .
translocation", "2005 .
translocation of", ".
translocation of runx2", "of runx2 protein", "runx2 protein to", "protein to the", "to the nucleus", "the nucleus is", "nucleus is inhibited", "binding to non", "to non activated", "non activated stat1", "stat1 kim", "kim et al.", "et al. 2003", "al. 2003 .
several", "2003 .
several e3", ".
several e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases were", "ligases were shown", "were shown to", "shown to polyubiquitinate", "to polyubiquitinate runx2", "runx2 targeting", "targeting it for", "it for proteasome", "for proteasome mediated", "proteasome mediated degradation:", "mediated degradation: stub1", "stub1 chip", "li et al.", "et al. 2008", "smurf1 zhao", "zhao et al.", "2003 yang", "et al. 2014", "wwp1 jones", "skp2 thacker", "thacker et al.", "et al. 2016", "al. 2016 .", "several transcription factors have", "transcription factors have been", "factors have been implicated", "have been implicated in", "been implicated in regulation", "implicated in regulation of", "in regulation of the", "regulation of the runx2", "of the runx2 gene", "the runx2 gene transcription.", "runx2 gene transcription. similar", "gene transcription. similar to", "transcription. similar to the", "similar to the runx1", "to the runx1 gene", "runx1 gene the", "gene the runx2", "the runx2 gene expression", "runx2 gene expression can", "gene expression can be", "expression can be regulated", "can be regulated from", "be regulated from the", "regulated from the proximal", "from the proximal p2", "the proximal p2 promoter", "proximal p2 promoter or", "p2 promoter or the", "promoter or the distal", "or the distal p1", "the distal p1 promoter", "p1 promoter reviewed", "promoter reviewed in", "reviewed in li and", "in li and xiao", "li and xiao 2007", "and xiao 2007 .
activated", "xiao 2007 .
activated estrogen", "2007 .
activated estrogen receptor", ".
activated estrogen receptor alpha", "receptor alpha esr1", "esr1 binds estrogen", "binds estrogen response elements", "response elements eres", "eres in the", "in the p2 promoter", "the p2 promoter and", "p2 promoter and stimulates", "promoter and stimulates runx2", "and stimulates runx2 transcription", "runx2 transcription kammerer", "transcription kammerer et", "kammerer et al. 2013", "et al. 2013 .", "al. 2013 . estrogen", "2013 . estrogen related", ". estrogen related receptor", "estrogen related receptor alpha", "receptor alpha erra", "erra binds eres", "binds eres or estrogen", "eres or estrogen related", "or estrogen related response", "estrogen related response elements", "response elements erres", "erres in the", "the p2 promoter of", "p2 promoter of runx2.", "promoter of runx2. when", "of runx2. when erra", "runx2. when erra is", "when erra is bound", "erra is bound to", "is bound to its", "bound to its co", "to its co factor", "its co factor pparg1ca", "factor pparg1ca pgc1a", "pgc1a it", "it stimulates runx2 transcription.", "stimulates runx2 transcription. when", "runx2 transcription. when bound", "transcription. when bound to", "when bound to its", "its co factor pparg1cb", "factor pparg1cb pgc1b", "pgc1b erra", "erra represses runx2 transcription", "et al. 2013 .
twist1", "2013 .
twist1 a", ".
twist1 a basic", "a basic helix loop", "basic helix loop helix", "loop helix bhlh", "bhlh transcription factor", "transcription factor stimulates", "factor stimulates runx2", "stimulates runx2 transcription by", "runx2 transcription by binding", "transcription by binding to", "by binding to the", "binding to the e1", "to the e1 box", "the e1 box in", "e1 box in the", "box in the p2", "p2 promoter yang", "yang yang et", "yang et al. 2011", "et al. 2011 .", "al. 2011 . twist", "2011 . twist proteins", ". twist proteins also", "twist proteins also interact", "proteins also interact with", "also interact with the", "interact with the dna", "with the dna binding", "the dna binding domain", "dna binding domain of", "binding domain of runx2", "domain of runx2 to", "of runx2 to modulate", "runx2 to modulate its", "to modulate its activity", "modulate its activity during", "its activity during skeletogenesis", "during skeletogenesis bialek", "skeletogenesis bialek et", "bialek et al. 2004", "et al. 2004 .", "al. 2004 . schnurri", "2004 . schnurri 3", "schnurri 3 shn3", "shn3 is another", "is another protein that", "another protein that interacts", "protein that interacts with", "that interacts with runx2", "interacts with runx2 to", "with runx2 to decrease", "runx2 to decrease its", "to decrease its availability", "decrease its availability in", "its availability in the", "availability in the nucleus", "in the nucleus and", "the nucleus and therefore", "nucleus and therefore its", "and therefore its activity", "its activity jones", "activity jones et", "jones et al. 2006", "et al. 2006 .", "al. 2006 . in", "2006 . in contrast", "in contrast runx2", "contrast runx2 and", "runx2 and satb2 interact", "and satb2 interact to", "satb2 interact to enhance", "interact to enhance the", "to enhance the expression", "enhance the expression of", "the expression of osteoblast", "expression of osteoblast specific", "of osteoblast specific genes", "specific genes dobreva", "genes dobreva et", "dobreva et al. 2006", "al. 2006 . formation", "2006 . formation of", ". formation of the", "formation of the heterodimer", "of the heterodimer with", "the heterodimer with cbfb", "with cbfb cbf", "cbfb cbf beta", "cbf beta also", "beta also enhances", "also enhances the transcriptional", "enhances the transcriptional activity", "the transcriptional activity of", "transcriptional activity of runx2", "of runx2 kundu", "runx2 kundu et", "kundu et al. 2002", "al. 2002 yoshida", "2002 yoshida et", "yoshida et al. 2002", "al. 2002 otto", "2002 otto et", "otto et al. 2002", "et al. 2002 .
transcription", "al. 2002 .
transcription of", "2002 .
transcription of runx2", ".
transcription of runx2 from", "of runx2 from the", "runx2 from the proximal", "from the proximal promoter", "the proximal promoter is", "proximal promoter is inhibited", "promoter is inhibited by", "is inhibited by binding", "inhibited by binding of", "by binding of the", "binding of the glucocorticoid", "of the glucocorticoid receptor", "glucocorticoid receptor nr3c1", "nr3c1 activated by", "by dexamethasone dexa", "dexa to a", "to a glucocorticoid receptor", "a glucocorticoid receptor response", "glucocorticoid receptor response element", "response element gre", "gre which", "which is also present", "is also present in", "also present in the", "present in the human", "in the human promoter", "human promoter zhang", "promoter zhang et", "zhang et al. 2012", "et al. 2012 .
nkx3", "al. 2012 .
nkx3 2", ".
nkx3 2 bapx1", "bapx1 required", "required for embryonic development", "for embryonic development of", "embryonic development of the", "development of the axial", "of the axial skeleton", "axial skeleton tribioli", "skeleton tribioli and", "tribioli and lufkin 1999", "1999 binds", "promoter of the runx2", "the runx2 gene and", "runx2 gene and inhibits", "gene and inhibits its", "and inhibits its transcription", "its transcription lengner", "transcription lengner et", "lengner et al. 2005", "et al. 2005 .", "al. 2005 . runx2", "2005 . runx2 p1", ". runx2 p1 transcription", "runx2 p1 transcription is", "p1 transcription is also", "transcription is also autoinhibited", "is also autoinhibited by", "also autoinhibited by runx2", "autoinhibited by runx2 p1", "runx2 p1 which", "p1 which binds", "which binds to runx2", "binds to runx2 response", "to runx2 response elements", "runx2 response elements in", "response elements in the", "elements in the p1", "in the p1 promoter", "the p1 promoter of", "p1 promoter of runx2", "of runx2 drissi", "runx2 drissi et", "drissi et al. 2000", "et al. 2000 .", "al. 2000 . in", "2000 . in contrast", "in contrast binding", "contrast binding of", "binding of runx2 p2", "of runx2 p2 to", "runx2 p2 to the", "p2 to the proximal", "to the proximal p2", "proximal p2 promoter autoactivates", "p2 promoter autoactivates transcription", "promoter autoactivates transcription of", "autoactivates transcription of runx2", "transcription of runx2 p2", "runx2 p2 ducy", "p2 ducy et", "ducy et al. 1999", "et al. 1999 .", "al. 1999 . binding", "1999 . binding of", ". binding of a", "binding of a homeodomain", "of a homeodomain transcription", "a homeodomain transcription factor", "homeodomain transcription factor dlx5", "factor dlx5 and", "dlx5 and possibly", "possibly dlx6 to", "dlx6 to the", "to the runx2 p1", "the runx2 p1 promoter", "runx2 p1 promoter stimulates", "p1 promoter stimulates runx2", "promoter stimulates runx2 transcription", "runx2 transcription robledo", "transcription robledo et", "robledo et al. 2002", "al. 2002 lee", "2002 lee et", "lee et al. 2005", "al. 2005 . the", "2005 . the homeobox", ". the homeobox transcription", "the homeobox transcription factor", "homeobox transcription factor msx2", "transcription factor msx2 can", "factor msx2 can bind", "msx2 can bind to", "can bind to dlx5", "bind to dlx5 sites", "to dlx5 sites in", "dlx5 sites in the", "sites in the promoter", "in the promoter of", "the promoter of runx2", "promoter of runx2 and", "of runx2 and inhibit", "runx2 and inhibit transcription", "and inhibit transcription of", "inhibit transcription of runx2", "transcription of runx2 p1", "runx2 p1 lee", "p1 lee et", "et al. 2005 .
translocation", "al. 2005 .
translocation of", "2005 .
translocation of runx2", ".
translocation of runx2 protein", "of runx2 protein to", "runx2 protein to the", "protein to the nucleus", "to the nucleus is", "the nucleus is inhibited", "nucleus is inhibited by", "inhibited by binding to", "by binding to non", "binding to non activated", "to non activated stat1", "activated stat1 kim", "stat1 kim et", "kim et al. 2003", "et al. 2003 .
several", "al. 2003 .
several e3", "2003 .
several e3 ubiquitin", ".
several e3 ubiquitin ligases", "e3 ubiquitin ligases were", "ubiquitin ligases were shown", "ligases were shown to", "were shown to polyubiquitinate", "shown to polyubiquitinate runx2", "polyubiquitinate runx2 targeting", "runx2 targeting it", "targeting it for proteasome", "it for proteasome mediated", "for proteasome mediated degradation:", "proteasome mediated degradation: stub1", "degradation: stub1 chip", "chip li", "li et al. 2008", "2008 smurf1", "smurf1 zhao et", "zhao et al. 2003", "al. 2003 yang", "2003 yang et", "yang et al. 2014", "2014 wwp1", "wwp1 jones et", "2006 and", "and skp2 thacker", "skp2 thacker et", "thacker et al. 2016", "et al. 2016 .", "several transcription factors have been", "transcription factors have been implicated", "factors have been implicated in", "have been implicated in regulation", "been implicated in regulation of", "implicated in regulation of the", "in regulation of the runx2", "regulation of the runx2 gene", "of the runx2 gene transcription.", "the runx2 gene transcription. similar", "runx2 gene transcription. similar to", "gene transcription. similar to the", "transcription. similar to the runx1", "similar to the runx1 gene", "the runx1 gene the", "runx1 gene the runx2", "gene the runx2 gene", "the runx2 gene expression can", "runx2 gene expression can be", "gene expression can be regulated", "expression can be regulated from", "can be regulated from the", "be regulated from the proximal", "regulated from the proximal p2", "from the proximal p2 promoter", "the proximal p2 promoter or", "proximal p2 promoter or the", "p2 promoter or the distal", "promoter or the distal p1", "or the distal p1 promoter", "distal p1 promoter reviewed", "p1 promoter reviewed in", "promoter reviewed in li", "reviewed in li and xiao", "in li and xiao 2007", "li and xiao 2007 .
activated", "and xiao 2007 .
activated estrogen", "xiao 2007 .
activated estrogen receptor", "2007 .
activated estrogen receptor alpha", "estrogen receptor alpha esr1", "alpha esr1 binds", "esr1 binds estrogen response", "estrogen response elements eres", "elements eres in", "eres in the p2", "in the p2 promoter and", "the p2 promoter and stimulates", "p2 promoter and stimulates runx2", "promoter and stimulates runx2 transcription", "stimulates runx2 transcription kammerer", "runx2 transcription kammerer et", "transcription kammerer et al.", "kammerer et al. 2013 .", "et al. 2013 . estrogen", "al. 2013 . estrogen related", "2013 . estrogen related receptor", ". estrogen related receptor alpha", "related receptor alpha erra", "alpha erra binds", "erra binds eres or", "binds eres or estrogen related", "eres or estrogen related response", "or estrogen related response elements", "related response elements erres", "elements erres in", "erres in the p2", "in the p2 promoter of", "the p2 promoter of runx2.", "p2 promoter of runx2. when", "promoter of runx2. when erra", "of runx2. when erra is", "runx2. when erra is bound", "when erra is bound to", "erra is bound to its", "is bound to its co", "bound to its co factor", "to its co factor pparg1ca", "co factor pparg1ca pgc1a", "pgc1a it stimulates", "it stimulates runx2 transcription. when", "stimulates runx2 transcription. when bound", "runx2 transcription. when bound to", "transcription. when bound to its", "when bound to its co", "to its co factor pparg1cb", "co factor pparg1cb pgc1b", "pgc1b erra represses", "represses runx2 transcription kammerer", "kammerer et al. 2013 .
twist1", "al. 2013 .
twist1 a", "2013 .
twist1 a basic", ".
twist1 a basic helix", "a basic helix loop helix", "helix loop helix bhlh", "helix bhlh transcription", "transcription factor stimulates runx2", "factor stimulates runx2 transcription", "stimulates runx2 transcription by binding", "runx2 transcription by binding to", "transcription by binding to the", "by binding to the e1", "binding to the e1 box", "to the e1 box in", "the e1 box in the", "e1 box in the p2", "box in the p2 promoter", "the p2 promoter yang", "promoter yang yang", "yang yang et al.", "yang et al. 2011 .", "et al. 2011 . twist", "al. 2011 . twist proteins", "2011 . twist proteins also", ". twist proteins also interact", "twist proteins also interact with", "proteins also interact with the", "also interact with the dna", "interact with the dna binding", "with the dna binding domain", "the dna binding domain of", "dna binding domain of runx2", "binding domain of runx2 to", "domain of runx2 to modulate", "of runx2 to modulate its", "runx2 to modulate its activity", "to modulate its activity during", "modulate its activity during skeletogenesis", "activity during skeletogenesis bialek", "during skeletogenesis bialek et", "skeletogenesis bialek et al.", "bialek et al. 2004 .", "et al. 2004 . schnurri", "al. 2004 . schnurri 3", ". schnurri 3 shn3", "3 shn3 is", "shn3 is another protein", "is another protein that interacts", "another protein that interacts with", "protein that interacts with runx2", "that interacts with runx2 to", "interacts with runx2 to decrease", "with runx2 to decrease its", "runx2 to decrease its availability", "to decrease its availability in", "decrease its availability in the", "its availability in the nucleus", "availability in the nucleus and", "in the nucleus and therefore", "the nucleus and therefore its", "nucleus and therefore its activity", "therefore its activity jones", "its activity jones et", "activity jones et al.", "jones et al. 2006 .", "et al. 2006 . in", "al. 2006 . in contrast", ". in contrast runx2", "in contrast runx2 and", "contrast runx2 and satb2", "runx2 and satb2 interact to", "and satb2 interact to enhance", "satb2 interact to enhance the", "interact to enhance the expression", "to enhance the expression of", "enhance the expression of osteoblast", "the expression of osteoblast specific", "expression of osteoblast specific genes", "osteoblast specific genes dobreva", "specific genes dobreva et", "genes dobreva et al.", "dobreva et al. 2006 .", "et al. 2006 . formation", "al. 2006 . formation of", "2006 . formation of the", ". formation of the heterodimer", "formation of the heterodimer with", "of the heterodimer with cbfb", "heterodimer with cbfb cbf", "with cbfb cbf beta", "cbf beta also enhances", "beta also enhances the", "also enhances the transcriptional activity", "enhances the transcriptional activity of", "the transcriptional activity of runx2", "activity of runx2 kundu", "of runx2 kundu et", "runx2 kundu et al.", "et al. 2002 yoshida", "al. 2002 yoshida et", "2002 yoshida et al.", "et al. 2002 otto", "al. 2002 otto et", "2002 otto et al.", "otto et al. 2002 .
transcription", "et al. 2002 .
transcription of", "al. 2002 .
transcription of runx2", "2002 .
transcription of runx2 from", ".
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nkx3", "et al. 2012 .
nkx3 2", "2012 .
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translocation", "et al. 2005 .
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several", "et al. 2003 .
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several e3 ubiquitin", "2003 .
several e3 ubiquitin ligases", ".
several e3 ubiquitin ligases were", "e3 ubiquitin ligases were shown", "ubiquitin ligases were shown to", "ligases were shown to polyubiquitinate", "were shown to polyubiquitinate runx2", "to polyubiquitinate runx2 targeting", "polyubiquitinate runx2 targeting it", "runx2 targeting it for", "targeting it for proteasome mediated", "it for proteasome mediated degradation:", "for proteasome mediated degradation: stub1", "mediated degradation: stub1 chip", "chip li et", "al. 2008 smurf1", "smurf1 zhao et al.", "et al. 2003 yang", "al. 2003 yang et", "2003 yang et al.", "al. 2014 wwp1", "wwp1 jones et al.", "al. 2006 and", "2006 and skp2", "and skp2 thacker et", "skp2 thacker et al.", "thacker et al. 2016 ." ] }, { "record_id": "GLY_000594_1_639", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8940973", "r hsa", "hsa 8940973", "r hsa 8940973" ] }, { "record_id": "GLY_000594_1_639", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "runx2 regulates", "regulates osteoblast", "osteoblast differentiation", "runx2 regulates osteoblast", "regulates osteoblast differentiation", "runx2 regulates osteoblast differentiation", "the complex", "complex of", "of runx2", "runx2 and", "and cbfb", "cbfb regulates", "regulates transcription", "transcription of", "of genes", "genes involved", "involved in", "in differentiation", "differentiation of", "of osteoblasts.
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runx3 protein", "protein levels", "levels are", "are inversely", "inversely related", "related to", "to the", "the levels", "levels of", "of microrna", "microrna mir", "mir 130b.", "130b. based", "based on", "on in", "in silico", "silico analysis", "runx3 is", "is predicted", "predicted to", "to be", "be the", "the target", "target of", "of mir", "mir 130b", "but binding", "binding assays", "assays and", "and 3'utr", "3'utr reporter", "reporter assays", "assays have", "have not", "not been", "been done", "done to", "to confirm", "confirm this", "lai et", "al. 2010", "paudel et", "al. 2016", "2016 .
similar", ".
similar to", "to runx1", "runx1 and", "and runx2", "runx3 forms", "forms a", "a transcriptionally", "transcriptionally active", "active heterodimer", "heterodimer with", "with cbfb", "cbf beta", "kim et", "al. 2013", "2013 .", "runx3 activity", "activity can", "can be", "be regulated", "regulated by", "by changes", "changes in", "in runx3", "runx3 localization.", "localization. src", "src protein", "protein tyrosine", "tyrosine kinase", "kinase phosphorylates", "phosphorylates runx3", "runx3 on", "on multiple", "multiple tyrosine", "tyrosine residues", "inhibiting its", "its translocation", "translocation from", "from the", "the cytosol", "cytosol to", "the nucleus", "nucleus and", "and thus", "thus inhibiting", "inhibiting runx3", "runx3 mediated", "mediated transcription", "goh et", "2010 .", ". subcellular", "subcellular localization", "localization of", "may be", "be affected", "by pim1", "pim1 mediated", "mediated phosphorylation", "al. 2008", "2008 .
the", ".
the p1", "p1 and", "and p2", "p2 promoters", "promoters regulate", "regulate runx3", "transcription in", "in a", "a cell", "cell type/differentiation", "type/differentiation dependent", "dependent manner", "giving rise", "rise to", "the p44", "p44 and", "and p46", "p46 isoforms", "isoforms of", "respectively. several", "several splicing", "splicing isoforms", "isoforms have", "have also", "also been", "been reported.", "reported. one", "one example", "example is", "is the", "the generation", "generation of", "of a", "a 33", "33 kda", "kda protein", "protein isoform", "by alternative", "alternative splicing.", "splicing. the", "runx3 p33", "p33 isoform", "isoform lacks", "lacks the", "the runt", "runt domain", "domain and", "and is", "is unable", "unable to", "to transactivate", "transactivate the", "the regulatory", "regulatory regions", "regions of", "of integrin", "integrin genes.", "genes. the", "the p33", "isoform is", "is induced", "induced during", "during maturation", "maturation of", "of monocyte", "monocyte derived", "derived dendritic", "dendritic cells", "leading to", "to reduced", "reduced expression", "expression of", "of genes", "genes involved", "involved in", "in inflammatory", "inflammatory responses", "such as", "as il8", "interleukin 8", "puig kroger", "kroger et", "2010 .
e3", ".
e3 ubiquitin", "ubiquitin ligases", "ligases mdm2", "chi et", "smurf1 and", "and smurf2", "jin et", "al. 2004", "are implicated", "implicated in", "runx3 polyubiquitination", "polyubiquitination and", "and degradation.", "runx3 like", "like other runx", "other runx family", "runx family members", "members is", "is transcribed from", "transcribed from two", "from two promoters", "the proximal p2", "proximal p2 promoter", "p2 promoter and", "promoter and the", "and the distal", "the distal p1", "distal p1 promoter.", "p1 promoter. the", "promoter. the p2", "the p2 promoter", "p2 promoter is", "promoter is positioned", "is positioned within", "positioned within a", "within a large", "a large cpg", "large cpg island", "cpg island that", "island that is", "that is frequently", "is frequently methylated", "frequently methylated in", "methylated in solid", "in solid tumors", "tumors resulting", "resulting in epigenetic", "in epigenetic inactivation", "epigenetic inactivation of", "inactivation of the", "of the runx3", "the runx3 gene", "gene reviewed", "reviewed by levanon", "by levanon and", "levanon and groner", "and groner 2004", "groner 2004 .", "2004 . runx3", ". runx3 transcription", "runx3 transcription is", "transcription is affected", "is affected by", "affected by smad4", "by smad4 levels.", "smad4 levels. runx3", "levels. runx3 may", "runx3 may directly", "may directly upregulate", "directly upregulate its", "upregulate its own", "its own transcription", "own transcription through", "transcription through a", "through a positive", "a positive feedback", "positive feedback loop", "loop whittle", "whittle et al.", "et al. 2015", "al. 2015 .", "2015 . under", ". under hypoxic", "under hypoxic conditions", "conditions runx3", "transcription is downregulated.", "is downregulated. hypoxic", "downregulated. hypoxic silencing", "hypoxic silencing of", "silencing of runx3", "of runx3 involves", "runx3 involves hypoxia", "involves hypoxia induced", "hypoxia induced upregulation", "induced upregulation of", "upregulation of the", "of the histone", "the histone methyltransferase", "histone methyltransferase g9a", "methyltransferase g9a and", "g9a and histone", "and histone deacetylase", "histone deacetylase hdac1", "hdac1 which", "which leads to", "leads to increased", "to increased dimethylation", "increased dimethylation of", "dimethylation of histone", "of histone h3", "histone h3 at", "h3 at lysine", "at lysine residue", "lysine residue k9", "k9 k10", "k10 when taking", "when taking into", "taking into account", "into account the", "account the initiator", "the initiator methionine", "methionine and", "and reduced acetylation", "reduced acetylation of", "acetylation of histone", "h3 at the", "at the runx3", "the runx3 promoter", "promoter lee", "lee et al.", "et al. 2009", "al. 2009 .
runx3", "2009 .
runx3 protein", ".
runx3 protein levels", "protein levels are", "levels are inversely", "are inversely related", "inversely related to", "related to the", "to the levels", "the levels of", "levels of microrna", "of microrna mir", "microrna mir 130b.", "mir 130b. based", "130b. based on", "based on in", "on in silico", "in silico analysis", "analysis runx3", "runx3 is predicted", "is predicted to", "predicted to be", "to be the", "be the target", "the target of", "target of mir", "of mir 130b", "130b but", "but binding assays", "binding assays and", "assays and 3'utr", "and 3'utr reporter", "3'utr reporter assays", "reporter assays have", "assays have not", "have not been", "not been done", "been done to", "done to confirm", "to confirm this", "this lai", "lai et al.", "et al. 2010", "2010 paudel", "paudel et al.", "et al. 2016", "al. 2016 .
similar", "2016 .
similar to", ".
similar to runx1", "to runx1 and", "runx1 and runx2", "runx2 runx3", "runx3 forms a", "forms a transcriptionally", "a transcriptionally active", "transcriptionally active heterodimer", "active heterodimer with", "heterodimer with cbfb", "cbfb cbf", "kim et al.", "et al. 2013", "al. 2013 .", "2013 . runx3", ". runx3 activity", "runx3 activity can", "activity can be", "can be regulated", "be regulated by", "regulated by changes", "by changes in", "changes in runx3", "in runx3 localization.", "runx3 localization. src", "localization. src protein", "src protein tyrosine", "protein tyrosine kinase", "tyrosine kinase phosphorylates", "kinase phosphorylates runx3", "phosphorylates runx3 on", "runx3 on multiple", "on multiple tyrosine", "multiple tyrosine residues", "residues inhibiting", "inhibiting its translocation", "its translocation from", "translocation from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the nucleus", "the nucleus and", "nucleus and thus", "and thus inhibiting", "thus inhibiting runx3", "inhibiting runx3 mediated", "runx3 mediated transcription", "transcription goh", "goh et al.", "al. 2010 .", "2010 . subcellular", ". subcellular localization", "subcellular localization of", "localization of runx3", "of runx3 may", "runx3 may be", "may be affected", "be affected by", "affected by pim1", "by pim1 mediated", "pim1 mediated phosphorylation", "phosphorylation kim", "et al. 2008", "al. 2008 .
the", "2008 .
the p1", ".
the p1 and", "p1 and p2", "and p2 promoters", "p2 promoters regulate", "promoters regulate runx3", "regulate runx3 transcription", "runx3 transcription in", "transcription in a", "in a cell", "a cell type/differentiation", "cell type/differentiation dependent", "type/differentiation dependent manner", "manner giving", "giving rise to", "rise to the", "to the p44", "the p44 and", "p44 and p46", "and p46 isoforms", "p46 isoforms of", "isoforms of runx3", "runx3 respectively.", "respectively. several splicing", "several splicing isoforms", "splicing isoforms have", "isoforms have also", "have also been", "also been reported.", "been reported. one", "reported. one example", "one example is", "example is the", "is the generation", "the generation of", "generation of a", "of a 33", "a 33 kda", "33 kda protein", "kda protein isoform", "isoform p33", "p33 by", "by alternative splicing.", "alternative splicing. the", "splicing. the runx3", "the runx3 p33", "runx3 p33 isoform", "p33 isoform lacks", "isoform lacks the", "lacks the runt", "the runt domain", "runt domain and", "domain and is", "and is unable", "is unable to", "unable to transactivate", "to transactivate the", "transactivate the regulatory", "the regulatory regions", "regulatory regions of", "regions of integrin", "of integrin genes.", "integrin genes. the", "genes. the p33", "the p33 isoform", "p33 isoform is", "isoform is induced", "is induced during", "induced during maturation", "during maturation of", "maturation of monocyte", "of monocyte derived", "monocyte derived dendritic", "derived dendritic cells", "cells mddc", "leading to reduced", "to reduced expression", "reduced expression of", "expression of genes", "of genes involved", "genes involved in", "involved in inflammatory", "in inflammatory responses", "responses such", "such as il8", "il8 interleukin", "puig kroger et", "kroger et al.", "al. 2010 .
e3", "2010 .
e3 ubiquitin", ".
e3 ubiquitin ligases", "ubiquitin ligases mdm2", "mdm2 chi", "chi et al.", "smurf1 and smurf2", "smurf2 jin", "jin et al.", "et al. 2004", "2004 are", "are implicated in", "implicated in runx3", "in runx3 polyubiquitination", "runx3 polyubiquitination and", "polyubiquitination and degradation.", "runx3 like other", "like other runx family", "other runx family members", "family members is", "members is transcribed", "is transcribed from two", "transcribed from two promoters", "promoters the", "the proximal p2 promoter", "proximal p2 promoter and", "p2 promoter and the", "promoter and the distal", "and the distal p1", "the distal p1 promoter.", "distal p1 promoter. the", "p1 promoter. the p2", "promoter. the p2 promoter", "the p2 promoter is", "p2 promoter is positioned", "promoter is positioned within", "is positioned within a", "positioned within a large", "within a large cpg", "a large cpg island", "large cpg island that", "cpg island that is", "island that is frequently", "that is frequently methylated", "is frequently methylated in", "frequently methylated in solid", "methylated in solid tumors", "solid tumors resulting", "tumors resulting in", "resulting in epigenetic inactivation", "in epigenetic inactivation of", "epigenetic inactivation of the", "inactivation of the runx3", "of the runx3 gene", "runx3 gene reviewed", "gene reviewed by", "reviewed by levanon and", "by levanon and groner", "levanon and groner 2004", "and groner 2004 .", "groner 2004 . runx3", "2004 . runx3 transcription", ". runx3 transcription is", "runx3 transcription is affected", "transcription is affected by", "is affected by smad4", "affected by smad4 levels.", "by smad4 levels. runx3", "smad4 levels. runx3 may", "levels. runx3 may directly", "runx3 may directly upregulate", "may directly upregulate its", "directly upregulate its own", "upregulate its own transcription", "its own transcription through", "own transcription through a", "transcription through a positive", "through a positive feedback", "a positive feedback loop", "feedback loop whittle", "loop whittle et", "whittle et al. 2015", "et al. 2015 .", "al. 2015 . under", "2015 . under hypoxic", ". under hypoxic conditions", "hypoxic conditions runx3", "conditions runx3 transcription", "runx3 transcription is downregulated.", "transcription is downregulated. hypoxic", "is downregulated. hypoxic silencing", "downregulated. hypoxic silencing of", "hypoxic silencing of runx3", "silencing of runx3 involves", "of runx3 involves hypoxia", "runx3 involves hypoxia induced", "involves hypoxia induced upregulation", "hypoxia induced upregulation of", "induced upregulation of the", "upregulation of the histone", "of the histone methyltransferase", "the histone methyltransferase g9a", "histone methyltransferase g9a and", "methyltransferase g9a and histone", "g9a and histone deacetylase", "and histone deacetylase hdac1", "deacetylase hdac1 which", "hdac1 which leads", "which leads to increased", "leads to increased dimethylation", "to increased dimethylation of", "increased dimethylation of histone", "dimethylation of histone h3", "of histone h3 at", "histone h3 at lysine", "h3 at lysine residue", "at lysine residue k9", "residue k9 k10", "k9 k10 when", "k10 when taking into", "when taking into account", "taking into account the", "into account the initiator", "account the initiator methionine", "initiator methionine and", "methionine and reduced", "and reduced acetylation of", "reduced acetylation of histone", "acetylation of histone h3", "histone h3 at the", "h3 at the runx3", "at the runx3 promoter", "runx3 promoter lee", "promoter lee et", "lee et al. 2009", "et al. 2009 .
runx3", "al. 2009 .
runx3 protein", "2009 .
runx3 protein levels", ".
runx3 protein levels are", "protein levels are inversely", "levels are inversely related", "are inversely related to", "inversely related to the", "related to the levels", "to the levels of", "the levels of microrna", "levels of microrna mir", "of microrna mir 130b.", "microrna mir 130b. based", "mir 130b. based on", "130b. based on in", "based on in silico", "on in silico analysis", "silico analysis runx3", "analysis runx3 is", "runx3 is predicted to", "is predicted to be", "predicted to be the", "to be the target", "be the target of", "the target of mir", "target of mir 130b", "mir 130b but", "130b but binding", "but binding assays and", "binding assays and 3'utr", "assays and 3'utr reporter", "and 3'utr reporter assays", "3'utr reporter assays have", "reporter assays have not", "assays have not been", "have not been done", "not been done to", "been done to confirm", "done to confirm this", "confirm this lai", "this lai et", "lai et al. 2010", "al. 2010 paudel", "2010 paudel et", "paudel et al. 2016", "et al. 2016 .
similar", "al. 2016 .
similar to", "2016 .
similar to runx1", ".
similar to runx1 and", "to runx1 and runx2", "and runx2 runx3", "runx2 runx3 forms", "runx3 forms a transcriptionally", "forms a transcriptionally active", "a transcriptionally active heterodimer", "transcriptionally active heterodimer with", "active heterodimer with cbfb", "with cbfb cbf", "cbfb cbf beta", "beta kim", "kim et al. 2013", "et al. 2013 .", "al. 2013 . runx3", "2013 . runx3 activity", ". runx3 activity can", "runx3 activity can be", "activity can be regulated", "can be regulated by", "be regulated by changes", "regulated by changes in", "by changes in runx3", "changes in runx3 localization.", "in runx3 localization. src", "runx3 localization. src protein", "localization. src protein tyrosine", "src protein tyrosine kinase", "protein tyrosine kinase phosphorylates", "tyrosine kinase phosphorylates runx3", "kinase phosphorylates runx3 on", "phosphorylates runx3 on multiple", "runx3 on multiple tyrosine", "on multiple tyrosine residues", "tyrosine residues inhibiting", "residues inhibiting its", "inhibiting its translocation from", "its translocation from the", "translocation from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the nucleus", "to the nucleus and", "the nucleus and thus", "nucleus and thus inhibiting", "and thus inhibiting runx3", "thus inhibiting runx3 mediated", "inhibiting runx3 mediated transcription", "mediated transcription goh", "transcription goh et", "goh et al. 2010", "et al. 2010 .", "al. 2010 . subcellular", "2010 . subcellular localization", ". subcellular localization of", "subcellular localization of runx3", "localization of runx3 may", "of runx3 may be", "runx3 may be affected", "may be affected by", "be affected by pim1", "affected by pim1 mediated", "by pim1 mediated phosphorylation", "mediated phosphorylation kim", "phosphorylation kim et", "kim et al. 2008", "et al. 2008 .
the", "al. 2008 .
the p1", "2008 .
the p1 and", ".
the p1 and p2", "p1 and p2 promoters", "and p2 promoters regulate", "p2 promoters regulate runx3", "promoters regulate runx3 transcription", "regulate runx3 transcription in", "runx3 transcription in a", "transcription in a cell", "in a cell type/differentiation", "a cell type/differentiation dependent", "cell type/differentiation dependent manner", "dependent manner giving", "manner giving rise", "giving rise to the", "rise to the p44", "to the p44 and", "the p44 and p46", "p44 and p46 isoforms", "and p46 isoforms of", "p46 isoforms of runx3", "of runx3 respectively.", "runx3 respectively. several", "respectively. several splicing isoforms", "several splicing isoforms have", "splicing isoforms have also", "isoforms have also been", "have also been reported.", "also been reported. one", "been reported. one example", "reported. one example is", "one example is the", "example is the generation", "is the generation of", "the generation of a", "generation of a 33", "of a 33 kda", "a 33 kda protein", "33 kda protein isoform", "protein isoform p33", "p33 by alternative", "by alternative splicing. the", "alternative splicing. the runx3", "splicing. the runx3 p33", "the runx3 p33 isoform", "runx3 p33 isoform lacks", "p33 isoform lacks the", "isoform lacks the runt", "lacks the runt domain", "the runt domain and", "runt domain and is", "domain and is unable", "and is unable to", "is unable to transactivate", "unable to transactivate the", "to transactivate the regulatory", "transactivate the regulatory regions", "the regulatory regions of", "regulatory regions of integrin", "regions of integrin genes.", "of integrin genes. the", "integrin genes. the p33", "genes. the p33 isoform", "the p33 isoform is", "p33 isoform is induced", "isoform is induced during", "is induced during maturation", "induced during maturation of", "during maturation of monocyte", "maturation of monocyte derived", "of monocyte derived dendritic", "monocyte derived dendritic cells", "dendritic cells mddc", "mddc leading", "leading to reduced expression", "to reduced expression of", "reduced expression of genes", "expression of genes involved", "of genes involved in", "genes involved in inflammatory", "involved in inflammatory responses", "inflammatory responses such", "responses such as", "as il8 interleukin", "il8 interleukin 8", "8 puig", "puig kroger et al.", "kroger et al. 2010", "et al. 2010 .
e3", "al. 2010 .
e3 ubiquitin", "2010 .
e3 ubiquitin ligases", ".
e3 ubiquitin ligases mdm2", "ligases mdm2 chi", "mdm2 chi et", "chi et al. 2009", "2009 smurf1", "and smurf2 jin", "smurf2 jin et", "jin et al. 2004", "al. 2004 are", "2004 are implicated", "are implicated in runx3", "implicated in runx3 polyubiquitination", "in runx3 polyubiquitination and", "runx3 polyubiquitination and degradation.", "runx3 like other runx", "like other runx family members", "runx family members is", "family members is transcribed", "members is transcribed from", "is transcribed from two promoters", "two promoters the", "promoters the proximal", "the proximal p2 promoter and", "proximal p2 promoter and the", "p2 promoter and the distal", "promoter and the distal p1", "and the distal p1 promoter.", "the distal p1 promoter. the", "distal p1 promoter. the p2", "p1 promoter. the p2 promoter", "promoter. the p2 promoter is", "the p2 promoter is positioned", "p2 promoter is positioned within", "promoter is positioned within a", "is positioned within a large", "positioned within a large cpg", "within a large cpg island", "a large cpg island that", "large cpg island that is", "cpg island that is frequently", "island that is frequently methylated", "that is frequently methylated in", "is frequently methylated in solid", "frequently methylated in solid tumors", "in solid tumors resulting", "solid tumors resulting in", "tumors resulting in epigenetic", "resulting in epigenetic inactivation of", "in epigenetic inactivation of the", "epigenetic inactivation of the runx3", "inactivation of the runx3 gene", "the runx3 gene reviewed", "runx3 gene reviewed by", "gene reviewed by levanon", "reviewed by levanon and groner", "by levanon and groner 2004", "levanon and groner 2004 .", "and groner 2004 . runx3", "groner 2004 . runx3 transcription", "2004 . runx3 transcription is", ". runx3 transcription is affected", "runx3 transcription is affected by", "transcription is affected by smad4", "is affected by smad4 levels.", "affected by smad4 levels. runx3", "by smad4 levels. runx3 may", "smad4 levels. runx3 may directly", "levels. runx3 may directly upregulate", "runx3 may directly upregulate its", "may directly upregulate its own", "directly upregulate its own transcription", "upregulate its own transcription through", "its own transcription through a", "own transcription through a positive", "transcription through a positive feedback", "through a positive feedback loop", "positive feedback loop whittle", "feedback loop whittle et", "loop whittle et al.", "whittle et al. 2015 .", "et al. 2015 . under", "al. 2015 . under hypoxic", "2015 . under hypoxic conditions", "under hypoxic conditions runx3", "hypoxic conditions runx3 transcription", "conditions runx3 transcription is", "runx3 transcription is downregulated. hypoxic", "transcription is downregulated. hypoxic silencing", "is downregulated. hypoxic silencing of", "downregulated. hypoxic silencing of runx3", "hypoxic silencing of runx3 involves", "silencing of runx3 involves hypoxia", "of runx3 involves hypoxia induced", "runx3 involves hypoxia induced upregulation", "involves hypoxia induced upregulation of", "hypoxia induced upregulation of the", "induced upregulation of the histone", "upregulation of the histone methyltransferase", "of the histone methyltransferase g9a", "the histone methyltransferase g9a and", "histone methyltransferase g9a and histone", "methyltransferase g9a and histone deacetylase", "g9a and histone deacetylase hdac1", "histone deacetylase hdac1 which", "deacetylase hdac1 which leads", "hdac1 which leads to", "which leads to increased dimethylation", "leads to increased dimethylation of", "to increased dimethylation of histone", "increased dimethylation of histone h3", "dimethylation of histone h3 at", "of histone h3 at lysine", "histone h3 at lysine residue", "h3 at lysine residue k9", "lysine residue k9 k10", "residue k9 k10 when", "k9 k10 when taking", "k10 when taking into account", "when taking into account the", "taking into account the initiator", "into account the initiator methionine", "the initiator methionine and", "initiator methionine and reduced", "methionine and reduced acetylation", "and reduced acetylation of histone", "reduced acetylation of histone h3", "acetylation of histone h3 at", "of histone h3 at the", "histone h3 at the runx3", "h3 at the runx3 promoter", "the runx3 promoter lee", "runx3 promoter lee et", "promoter lee et al.", "lee et al. 2009 .
runx3", "et al. 2009 .
runx3 protein", "al. 2009 .
runx3 protein levels", "2009 .
runx3 protein levels are", ".
runx3 protein levels are inversely", "protein levels are inversely related", "levels are inversely related to", "are inversely related to the", "inversely related to the levels", "related to the levels of", "to the levels of microrna", "the levels of microrna mir", "levels of microrna mir 130b.", "of microrna mir 130b. based", "microrna mir 130b. based on", "mir 130b. based on in", "130b. based on in silico", "based on in silico analysis", "in silico analysis runx3", "silico analysis runx3 is", "analysis runx3 is predicted", "runx3 is predicted to be", "is predicted to be the", "predicted to be the target", "to be the target of", "be the target of mir", "the target of mir 130b", "of mir 130b but", "mir 130b but binding", "130b but binding assays", "but binding assays and 3'utr", "binding assays and 3'utr reporter", "assays and 3'utr reporter assays", "and 3'utr reporter assays have", "3'utr reporter assays have not", "reporter assays have not been", "assays have not been done", "have not been done to", "not been done to confirm", "been done to confirm this", "to confirm this lai", "confirm this lai et", "this lai et al.", "et al. 2010 paudel", "al. 2010 paudel et", "2010 paudel et al.", "paudel et al. 2016 .
similar", "et al. 2016 .
similar to", "al. 2016 .
similar to runx1", "2016 .
similar to runx1 and", ".
similar to runx1 and runx2", "runx1 and runx2 runx3", "and runx2 runx3 forms", "runx2 runx3 forms a", "runx3 forms a transcriptionally active", "forms a transcriptionally active heterodimer", "a transcriptionally active heterodimer with", "transcriptionally active heterodimer with cbfb", "heterodimer with cbfb cbf", "with cbfb cbf beta", "cbf beta kim", "beta kim et", "kim et al. 2013 .", "et al. 2013 . runx3", "al. 2013 . runx3 activity", "2013 . runx3 activity can", ". runx3 activity can be", "runx3 activity can be regulated", "activity can be regulated by", "can be regulated by changes", "be regulated by changes in", "regulated by changes in runx3", "by changes in runx3 localization.", "changes in runx3 localization. src", "in runx3 localization. src protein", "runx3 localization. src protein tyrosine", "localization. src protein tyrosine kinase", "src protein tyrosine kinase phosphorylates", "protein tyrosine kinase phosphorylates runx3", "tyrosine kinase phosphorylates runx3 on", "kinase phosphorylates runx3 on multiple", "phosphorylates runx3 on multiple tyrosine", "runx3 on multiple tyrosine residues", "multiple tyrosine residues inhibiting", "tyrosine residues inhibiting its", "residues inhibiting its translocation", "inhibiting its translocation from the", "its translocation from the cytosol", "translocation from the cytosol to", "from the cytosol to the", "the cytosol to the nucleus", "cytosol to the nucleus and", "to the nucleus and thus", "the nucleus and thus inhibiting", "nucleus and thus inhibiting runx3", "and thus inhibiting runx3 mediated", "thus inhibiting runx3 mediated transcription", "runx3 mediated transcription goh", "mediated transcription goh et", "transcription goh et al.", "goh et al. 2010 .", "et al. 2010 . subcellular", "al. 2010 . subcellular localization", "2010 . subcellular localization of", ". subcellular localization of runx3", "subcellular localization of runx3 may", "localization of runx3 may be", "of runx3 may be affected", "runx3 may be affected by", "may be affected by pim1", "be affected by pim1 mediated", "affected by pim1 mediated phosphorylation", "pim1 mediated phosphorylation kim", "mediated phosphorylation kim et", "phosphorylation kim et al.", "kim et al. 2008 .
the", "et al. 2008 .
the p1", "al. 2008 .
the p1 and", "2008 .
the p1 and p2", ".
the p1 and p2 promoters", "p1 and p2 promoters regulate", "and p2 promoters regulate runx3", "p2 promoters regulate runx3 transcription", "promoters regulate runx3 transcription in", "regulate runx3 transcription in a", "runx3 transcription in a cell", "transcription in a cell type/differentiation", "in a cell type/differentiation dependent", "a cell type/differentiation dependent manner", "type/differentiation dependent manner giving", "dependent manner giving rise", "manner giving rise to", "giving rise to the p44", "rise to the p44 and", "to the p44 and p46", "the p44 and p46 isoforms", "p44 and p46 isoforms of", "and p46 isoforms of runx3", "isoforms of runx3 respectively.", "of runx3 respectively. several", "runx3 respectively. several splicing", "respectively. several splicing isoforms have", "several splicing isoforms have also", "splicing isoforms have also been", "isoforms have also been reported.", "have also been reported. one", "also been reported. one example", "been reported. one example is", "reported. one example is the", "one example is the generation", "example is the generation of", "is the generation of a", "the generation of a 33", "generation of a 33 kda", "of a 33 kda protein", "a 33 kda protein isoform", "kda protein isoform p33", "isoform p33 by", "p33 by alternative splicing.", "by alternative splicing. the runx3", "alternative splicing. the runx3 p33", "splicing. the runx3 p33 isoform", "the runx3 p33 isoform lacks", "runx3 p33 isoform lacks the", "p33 isoform lacks the runt", "isoform lacks the runt domain", "lacks the runt domain and", "the runt domain and is", "runt domain and is unable", "domain and is unable to", "and is unable to transactivate", "is unable to transactivate the", "unable to transactivate the regulatory", "to transactivate the regulatory regions", "transactivate the regulatory regions of", "the regulatory regions of integrin", "regulatory regions of integrin genes.", "regions of integrin genes. the", "of integrin genes. the p33", "integrin genes. the p33 isoform", "genes. the p33 isoform is", "the p33 isoform is induced", "p33 isoform is induced during", "isoform is induced during maturation", "is induced during maturation of", "induced during maturation of monocyte", "during maturation of monocyte derived", "maturation of monocyte derived dendritic", "of monocyte derived dendritic cells", "derived dendritic cells mddc", "mddc leading to", "leading to reduced expression of", "to reduced expression of genes", "reduced expression of genes involved", "expression of genes involved in", "of genes involved in inflammatory", "genes involved in inflammatory responses", "in inflammatory responses such", "inflammatory responses such as", "responses such as il8", "such as il8 interleukin", "as il8 interleukin 8", "interleukin 8 puig", "8 puig kroger", "puig kroger et al. 2010", "kroger et al. 2010 .
e3", "et al. 2010 .
e3 ubiquitin", "al. 2010 .
e3 ubiquitin ligases", "2010 .
e3 ubiquitin ligases mdm2", "ubiquitin ligases mdm2 chi", "ligases mdm2 chi et", "mdm2 chi et al.", "al. 2009 smurf1", "2009 smurf1 and", "smurf1 and smurf2 jin", "and smurf2 jin et", "smurf2 jin et al.", "et al. 2004 are", "al. 2004 are implicated", "2004 are implicated in", "are implicated in runx3 polyubiquitination", "implicated in runx3 polyubiquitination and", "in runx3 polyubiquitination and degradation." ] }, { "record_id": "GLY_000594_1_641", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8943724", "r hsa", "hsa 8943724", "r hsa 8943724" ] }, { "record_id": "GLY_000594_1_641", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of pten", "pten gene", "gene transcription", "regulation of pten", "of pten gene", "pten gene transcription", "regulation of pten gene", "of pten gene transcription", "regulation of pten gene transcription", "transcription of", "of the", "the pten", "gene is", "is regulated", "regulated at", "at multiple", "multiple levels.", "levels. epigenetic", "epigenetic repression", "repression involves", "involves the", "the recruitment", "recruitment of", "of mi", "mi 2/nurd", "2/nurd upon", "upon sall4", "sall4 binding", "binding to", "to the", "pten promoter", "yang et", "et al.", "al. 2008", "lu et", "al. 2009", "or evi1", "evi1 mediated", "mediated recruitment", "the polycomb", "polycomb repressor", "repressor complex", "song et", "yoshimi et", "al. 2011", "2011 .", ". transcriptional", "transcriptional regulation", "regulation is", "is also", "also elicited", "elicited by", "by negative", "negative regulators", "including nr2e1:atn1", "atrophin 1", "c jun", "snail and", "and slug", "zhang et", "al. 2006", "vasudevan et", "al. 2007", "escriva et", "uygur et", "al. 2015", "and positive", "positive regulators", "regulators such", "such as", "as tp53", "egr1 or", "or pparg", "stambolic et", "al. 2001", "virolle et", "patel et", "shen et", "li et", "al. 2016", "2016 .", "transcription of the", "of the pten", "the pten gene", "pten gene is", "gene is regulated", "is regulated at", "regulated at multiple", "at multiple levels.", "multiple levels. epigenetic", "levels. epigenetic repression", "epigenetic repression involves", "repression involves the", "involves the recruitment", "the recruitment of", "recruitment of mi", "of mi 2/nurd", "mi 2/nurd upon", "2/nurd upon sall4", "upon sall4 binding", "sall4 binding to", "binding to the", "to the pten", "the pten promoter", "promoter yang", "yang et al.", "et al. 2008", "2008 lu", "lu et al.", "et al. 2009", "2009 or", "or evi1 mediated", "evi1 mediated recruitment", "mediated recruitment of", "recruitment of the", "of the polycomb", "the polycomb repressor", "polycomb repressor complex", "complex prc", "prc to", "promoter song", "song et al.", "2009 yoshimi", "yoshimi et al.", "et al. 2011", "al. 2011 .", "2011 . transcriptional", ". transcriptional regulation", "transcriptional regulation is", "regulation is also", "is also elicited", "also elicited by", "elicited by negative", "by negative regulators", "regulators including", "nr2e1:atn1 atrophin", "1 complex", "complex jun", "jun c", "snail and slug", "slug zhang", "zhang et al.", "et al. 2006", "2006 vasudevan", "vasudevan et al.", "et al. 2007", "2007 escriva", "escriva et al.", "2008 uygur", "uygur et al.", "et al. 2015", "2015 and", "and positive regulators", "positive regulators such", "regulators such as", "such as tp53", "tp53 p53", "maf1 atf2", "atf2 egr1", "egr1 or pparg", "pparg stambolic", "stambolic et al.", "et al. 2001", "2001 virolle", "virolle et al.", "2001 patel", "patel et al.", "2001 shen", "shen et al.", "2006 li", "li et al.", "et al. 2016", "al. 2016 .", "transcription of the pten", "of the pten gene", "the pten gene is", "pten gene is regulated", "gene is regulated at", "is regulated at multiple", "regulated at multiple levels.", "at multiple levels. epigenetic", "multiple levels. epigenetic repression", "levels. epigenetic repression involves", "epigenetic repression involves the", "repression involves the recruitment", "involves the recruitment of", "the recruitment of mi", "recruitment of mi 2/nurd", "of mi 2/nurd upon", "mi 2/nurd upon sall4", "2/nurd upon sall4 binding", "upon sall4 binding to", "sall4 binding to the", "binding to the pten", "to the pten promoter", "pten promoter yang", "promoter yang et", "yang et al. 2008", "al. 2008 lu", "2008 lu et", "lu et al. 2009", "al. 2009 or", "2009 or evi1", "or evi1 mediated recruitment", "evi1 mediated recruitment of", "mediated recruitment of the", "recruitment of the polycomb", "of the polycomb repressor", "the polycomb repressor complex", "repressor complex prc", "prc to the", "pten promoter song", "promoter song et", "song et al. 2009", "al. 2009 yoshimi", "2009 yoshimi et", "yoshimi et al. 2011", "et al. 2011 .", "al. 2011 . transcriptional", "2011 . transcriptional regulation", ". transcriptional regulation is", "transcriptional regulation is also", "regulation is also elicited", "is also elicited by", "also elicited by negative", "elicited by negative regulators", "negative regulators including", "regulators including nr2e1:atn1", "including nr2e1:atn1 atrophin", "nr2e1:atn1 atrophin 1", "atrophin 1 complex", "jun c jun", "jun snail", "and slug zhang", "slug zhang et", "zhang et al. 2006", "al. 2006 vasudevan", "2006 vasudevan et", "vasudevan et al. 2007", "al. 2007 escriva", "2007 escriva et", "escriva et al. 2008", "al. 2008 uygur", "2008 uygur et", "uygur et al. 2015", "al. 2015 and", "2015 and positive", "and positive regulators such", "positive regulators such as", "regulators such as tp53", "as tp53 p53", "p53 maf1", "atf2 egr1 or", "or pparg stambolic", "pparg stambolic et", "stambolic et al. 2001", "al. 2001 virolle", "2001 virolle et", "virolle et al. 2001", "al. 2001 patel", "2001 patel et", "patel et al. 2001", "al. 2001 shen", "2001 shen et", "shen et al. 2006", "al. 2006 li", "2006 li et", "li et al. 2016", "et al. 2016 .", "transcription of the pten gene", "of the pten gene is", "the pten gene is regulated", "pten gene is regulated at", "gene is regulated at multiple", "is regulated at multiple levels.", "regulated at multiple levels. epigenetic", "at multiple levels. epigenetic repression", "multiple levels. epigenetic repression involves", "levels. epigenetic repression involves the", "epigenetic repression involves the recruitment", "repression involves the recruitment of", "involves the recruitment of mi", "the recruitment of mi 2/nurd", "recruitment of mi 2/nurd upon", "of mi 2/nurd upon sall4", "mi 2/nurd upon sall4 binding", "2/nurd upon sall4 binding to", "upon sall4 binding to the", "sall4 binding to the pten", "binding to the pten promoter", "the pten promoter yang", "pten promoter yang et", "promoter yang et al.", "et al. 2008 lu", "al. 2008 lu et", "2008 lu et al.", "et al. 2009 or", "al. 2009 or evi1", "2009 or evi1 mediated", "or evi1 mediated recruitment of", "evi1 mediated recruitment of the", "mediated recruitment of the polycomb", "recruitment of the polycomb repressor", "of the polycomb repressor complex", "polycomb repressor complex prc", "complex prc to", "prc to the pten", "the pten promoter song", "pten promoter song et", "promoter song et al.", "et al. 2009 yoshimi", "al. 2009 yoshimi et", "2009 yoshimi et al.", "yoshimi et al. 2011 .", "et al. 2011 . transcriptional", "al. 2011 . transcriptional regulation", "2011 . transcriptional regulation is", ". transcriptional regulation is also", "transcriptional regulation is also elicited", "regulation is also elicited by", "is also elicited by negative", "also elicited by negative regulators", "by negative regulators including", "negative regulators including nr2e1:atn1", "including nr2e1:atn1 atrophin 1", "1 complex jun", "complex jun c", "c jun snail", "jun snail and", "snail and slug zhang", "and slug zhang et", "slug zhang et al.", "et al. 2006 vasudevan", "al. 2006 vasudevan et", "2006 vasudevan et al.", "et al. 2007 escriva", "al. 2007 escriva et", "2007 escriva et al.", "et al. 2008 uygur", "al. 2008 uygur et", "2008 uygur et al.", "et al. 2015 and", "al. 2015 and positive", "2015 and positive regulators", "and positive regulators such as", "positive regulators such as tp53", "such as tp53 p53", "maf1 atf2 egr1", "atf2 egr1 or pparg", "egr1 or pparg stambolic", "or pparg stambolic et", "pparg stambolic et al.", "et al. 2001 virolle", "al. 2001 virolle et", "2001 virolle et al.", "et al. 2001 patel", "al. 2001 patel et", "2001 patel et al.", "et al. 2001 shen", "al. 2001 shen et", "2001 shen et al.", "et al. 2006 li", "al. 2006 li et", "2006 li et al.", "li et al. 2016 ." ] }, { "record_id": "GLY_000594_1_642", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8948216", "r hsa", "hsa 8948216", "r hsa 8948216" ] }, { "record_id": "GLY_000594_1_642", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "collagen chain", "chain trimerization", "collagen chain trimerization", "the c", "c propeptides", "propeptides of", "of collagen", "collagen propeptide", "propeptide chains", "chains are", "are essential", "essential for", "for the", "the association", "association of", "of three", "three peptide", "peptide chains", "chains into", "into a", "a trimeric", "trimeric but", "non helical", "helical procollagen.", "procollagen. this", "this initial", "initial binding", "binding event", "event determines", "determines the", "the composition", "composition of", "of the", "the trimer", "brings the", "the individual", "individual chains", "into the", "the correct", "correct register", "register and", "and initiates", "initiates formation", "formation of", "the triple", "triple helix", "helix at", "at the", "c terminus", "which then", "then proceeds", "proceeds towards", "towards the", "the n", "n terminus", "terminus in", "in a", "a zipper", "zipper like", "like fashion", "engel &", "& prockop", "prockop 1991", "1991 .", ". most", "most early", "early refolding", "refolding studies", "studies were", "were performed", "performed with", "with collagen", "collagen type", "type iii", "which contains", "contains a", "a disulfide", "disulfide linkage", "linkage at", "terminus of", "of its", "its triple", "b\u00e4chinger et", "et al.", "al. 1978", "bruckner et", "that acts", "acts as", "as a", "a permanent", "permanent linker", "linker even", "even after", "after removal", "removal of", "the non", "non collagenous", "collagenous domains.", "domains.

mutations", "

mutations within", "within the", "propeptides further", "further suggest", "suggest that", "that they", "they are", "are crucial", "crucial for", "correct interaction", "interaction of", "the three", "three polypeptide", "polypeptide chains", "chains and", "and for", "for subsequent", "subsequent correct", "correct folding", "refs. in", "in boudko", "boudko et", "al. 2011", "2011 .", "the c propeptides", "c propeptides of", "propeptides of collagen", "of collagen propeptide", "collagen propeptide chains", "propeptide chains are", "chains are essential", "are essential for", "essential for the", "for the association", "the association of", "association of three", "of three peptide", "three peptide chains", "peptide chains into", "chains into a", "into a trimeric", "a trimeric but", "but non", "non helical procollagen.", "helical procollagen. this", "procollagen. this initial", "this initial binding", "initial binding event", "binding event determines", "event determines the", "determines the composition", "the composition of", "composition of the", "of the trimer", "trimer brings", "brings the individual", "the individual chains", "individual chains into", "chains into the", "into the correct", "the correct register", "correct register and", "register and initiates", "and initiates formation", "initiates formation of", "formation of the", "of the triple", "the triple helix", "triple helix at", "helix at the", "at the c", "the c terminus", "terminus which", "which then proceeds", "then proceeds towards", "proceeds towards the", "towards the n", "the n terminus", "n terminus in", "terminus in a", "in a zipper", "a zipper like", "zipper like fashion", "fashion engel", "engel & prockop", "& prockop 1991", "prockop 1991 .", "1991 . most", ". most early", "most early refolding", "early refolding studies", "refolding studies were", "studies were performed", "were performed with", "performed with collagen", "with collagen type", "collagen type iii", "iii which", "which contains a", "contains a disulfide", "a disulfide linkage", "disulfide linkage at", "linkage at the", "c terminus of", "terminus of its", "of its triple", "its triple helix", "helix b\u00e4chinger", "b\u00e4chinger et al.", "et al. 1978", "1978 bruckner", "bruckner et al.", "1978 that", "that acts as", "acts as a", "as a permanent", "a permanent linker", "permanent linker even", "linker even after", "even after removal", "after removal of", "removal of the", "of the non", "the non collagenous", "non collagenous domains.", "collagenous domains.

mutations", "domains.

mutations within", "

mutations within the", "within the c", "c propeptides further", "propeptides further suggest", "further suggest that", "suggest that they", "that they are", "they are crucial", "are crucial for", "crucial for the", "for the correct", "the correct interaction", "correct interaction of", "interaction of the", "of the three", "the three polypeptide", "three polypeptide chains", "polypeptide chains and", "chains and for", "and for subsequent", "for subsequent correct", "subsequent correct folding", "folding refs.", "refs. in boudko", "in boudko et", "boudko et al.", "et al. 2011", "al. 2011 .", "the c propeptides of", "c propeptides of collagen", "propeptides of collagen propeptide", "of collagen propeptide chains", "collagen propeptide chains are", "propeptide chains are essential", "chains are essential for", "are essential for the", "essential for the association", "for the association of", "the association of three", "association of three peptide", "of three peptide chains", "three peptide chains into", "peptide chains into a", "chains into a trimeric", "into a trimeric but", "trimeric but non", "but non helical", "non helical procollagen. this", "helical procollagen. this initial", "procollagen. this initial binding", "this initial binding event", "initial binding event determines", "binding event determines the", "event determines the composition", "determines the composition of", "the composition of the", "composition of the trimer", "the trimer brings", "trimer brings the", "brings the individual chains", "the individual chains into", "individual chains into the", "chains into the correct", "into the correct register", "the correct register and", "correct register and initiates", "register and initiates formation", "and initiates formation of", "initiates formation of the", "formation of the triple", "of the triple helix", "the triple helix at", "triple helix at the", "helix at the c", "at the c terminus", "c terminus which", "terminus which then", "which then proceeds towards", "then proceeds towards the", "proceeds towards the n", "towards the n terminus", "the n terminus in", "n terminus in a", "terminus in a zipper", "in a zipper like", "a zipper like fashion", "like fashion engel", "fashion engel &", "engel & prockop 1991", "& prockop 1991 .", "prockop 1991 . most", "1991 . most early", ". most early refolding", "most early refolding studies", "early refolding studies were", "refolding studies were performed", "studies were performed with", "were performed with collagen", "performed with collagen type", "with collagen type iii", "type iii which", "iii which contains", "which contains a disulfide", "contains a disulfide linkage", "a disulfide linkage at", "disulfide linkage at the", "linkage at the c", "the c terminus of", "c terminus of its", "terminus of its triple", "of its triple helix", "triple helix b\u00e4chinger", "helix b\u00e4chinger et", "b\u00e4chinger et al. 1978", "al. 1978 bruckner", "1978 bruckner et", "bruckner et al. 1978", "al. 1978 that", "1978 that acts", "that acts as a", "acts as a permanent", "as a permanent linker", "a permanent linker even", "permanent linker even after", "linker even after removal", "even after removal of", "after removal of the", "removal of the non", "of the non collagenous", "the non collagenous domains.", "non collagenous domains.

mutations", "collagenous domains.

mutations within", "domains.

mutations within the", "

mutations within the c", "within the c propeptides", "the c propeptides further", "c propeptides further suggest", "propeptides further suggest that", "further suggest that they", "suggest that they are", "that they are crucial", "they are crucial for", "are crucial for the", "crucial for the correct", "for the correct interaction", "the correct interaction of", "correct interaction of the", "interaction of the three", "of the three polypeptide", "the three polypeptide chains", "three polypeptide chains and", "polypeptide chains and for", "chains and for subsequent", "and for subsequent correct", "for subsequent correct folding", "correct folding refs.", "folding refs. in", "refs. in boudko et", "in boudko et al.", "boudko et al. 2011", "et al. 2011 .", "the c propeptides of collagen", "c propeptides of collagen propeptide", "propeptides of collagen propeptide chains", "of collagen propeptide chains are", "collagen propeptide chains are essential", "propeptide chains are essential for", "chains are essential for the", "are essential for the association", "essential for the association of", "for the association of three", "the association of three peptide", "association of three peptide chains", "of three peptide chains into", "three peptide chains into a", "peptide chains into a trimeric", "chains into a trimeric but", "a trimeric but non", "trimeric but non helical", "but non helical procollagen.", "non helical procollagen. this initial", "helical procollagen. this initial binding", "procollagen. this initial binding event", "this initial binding event determines", "initial binding event determines the", "binding event determines the composition", "event determines the composition of", "determines the composition of the", "the composition of the trimer", "of the trimer brings", "the trimer brings the", "trimer brings the individual", "brings the individual chains into", "the individual chains into the", "individual chains into the correct", "chains into the correct register", "into the correct register and", "the correct register and initiates", "correct register and initiates formation", "register and initiates formation of", "and initiates formation of the", "initiates formation of the triple", "formation of the triple helix", "of the triple helix at", "the triple helix at the", "triple helix at the c", "helix at the c terminus", "the c terminus which", "c terminus which then", "terminus which then proceeds", "which then proceeds towards the", "then proceeds towards the n", "proceeds towards the n terminus", "towards the n terminus in", "the n terminus in a", "n terminus in a zipper", "terminus in a zipper like", "in a zipper like fashion", "zipper like fashion engel", "like fashion engel &", "fashion engel & prockop", "engel & prockop 1991 .", "& prockop 1991 . most", "prockop 1991 . most early", "1991 . most early refolding", ". most early refolding studies", "most early refolding studies were", "early refolding studies were performed", "refolding studies were performed with", "studies were performed with collagen", "were performed with collagen type", "performed with collagen type iii", "collagen type iii which", "type iii which contains", "iii which contains a", "which contains a disulfide linkage", "contains a disulfide linkage at", "a disulfide linkage at the", "disulfide linkage at the c", "linkage at the c terminus", "at the c terminus of", "the c terminus of its", "c terminus of its triple", "terminus of its triple helix", "its triple helix b\u00e4chinger", "triple helix b\u00e4chinger et", "helix b\u00e4chinger et al.", "et al. 1978 bruckner", "al. 1978 bruckner et", "1978 bruckner et al.", "et al. 1978 that", "al. 1978 that acts", "1978 that acts as", "that acts as a permanent", "acts as a permanent linker", "as a permanent linker even", "a permanent linker even after", "permanent linker even after removal", "linker even after removal of", "even after removal of the", "after removal of the non", "removal of the non collagenous", "of the non collagenous domains.", "the non collagenous domains.

mutations", "non collagenous domains.

mutations within", "collagenous domains.

mutations within the", "domains.

mutations within the c", "

mutations within the c propeptides", "within the c propeptides further", "the c propeptides further suggest", "c propeptides further suggest that", "propeptides further suggest that they", "further suggest that they are", "suggest that they are crucial", "that they are crucial for", "they are crucial for the", "are crucial for the correct", "crucial for the correct interaction", "for the correct interaction of", "the correct interaction of the", "correct interaction of the three", "interaction of the three polypeptide", "of the three polypeptide chains", "the three polypeptide chains and", "three polypeptide chains and for", "polypeptide chains and for subsequent", "chains and for subsequent correct", "and for subsequent correct folding", "subsequent correct folding refs.", "correct folding refs. in", "folding refs. in boudko", "refs. in boudko et al.", "in boudko et al. 2011", "boudko et al. 2011 ." ] }, { "record_id": "GLY_000594_1_643", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8948751", "r hsa", "hsa 8948751", "r hsa 8948751" ] }, { "record_id": "GLY_000594_1_643", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of pten", "pten stability", "stability and", "and activity", "regulation of pten", "of pten stability", "pten stability and", "stability and activity", "regulation of pten stability", "of pten stability and", "pten stability and activity", "regulation of pten stability and", "of pten stability and activity", "pten protein", "protein stability", "stability is", "is regulated", "regulated by", "by ubiquitin", "ubiquitin ligases", "such as", "as nedd4", "mkrn1 and", "and rnf146", "which polyubiquitinate", "polyubiquitinate pten", "pten in", "in response", "response to", "to different", "different stimuli", "stimuli and", "and thus", "thus target", "target it", "it for", "for proteasome", "proteasome mediated", "mediated degradation", "wang et", "et al.", "al. 2007", "van themsche", "themsche et", "al. 2009", "maddika et", "al. 2011", "ahmed et", "al. 2012", "lee et", "al. 2015", "li et", "2015 .", ". several", "several ubiquitin", "ubiquitin proteases", "as usp13", "usp13 and", "and otud3", "can remove", "remove polyubiquitin", "polyubiquitin chains", "chains from", "from pten", "pten and", "and rescue", "rescue it", "it from", "from degradation", "zhang et", "al. 2013", "yuan et", ". trim27", "is an", "an e3", "e3 ubiquitin", "ubiquitin ligase", "ligase that", "that polyubiquitinates", "polyubiquitinates pten", "pten on", "on multiple", "multiple lysines", "lysines in", "in the", "the c2", "c2 domain", "domain of", "pten using", "using k27", "k27 linkage", "linkage between", "between ubiquitin", "ubiquitin molecules.", "molecules. trim27", "trim27 mediated", "mediated ubiquitination", "ubiquitination inhibits", "inhibits pten", "pten lipid", "lipid phosphatase", "phosphatase activity", "but does", "does not", "not affect", "affect pten", "protein localization", "localization or", "or stability", "2013 .
pten", ".
pten phosphorylation", "phosphorylation by", "by the", "the tyrosine", "tyrosine kinase", "kinase frk", "inhibits nedd4", "nedd4 mediated", "mediated polyubiquitination", "polyubiquitination and", "and subsequent", "subsequent degradation", "degradation of", "thus increasing", "increasing pten", "pten half", "half life.", "life. frk", "frk mediated", "mediated phosphorylation", "phosphorylation also", "also increases", "increases pten", "pten enzymatic", "enzymatic activity", "yim et", "2009 .", ". casein", "casein kinase", "kinase 2", "phosphorylation of", "of the", "the c", "c terminus", "terminus of", "multiple serine", "serine and", "and threonine", "threonine residues", "residues increases", "torres and", "and pulido", "pulido 2001", "but results", "results in", "in ~30%", "~30% reduction", "reduction in", "in pten", "miller et", "al. 2002", "2002 .
prex2", "a rac1", "rac1 guanine", "guanine nucleotide", "nucleotide exchange", "exchange factor", "can binds", "binds to", "to pten", "and inhibit", "inhibit its", "its catalytic", "catalytic activity", "fine et", "pten protein stability", "protein stability is", "stability is regulated", "is regulated by", "regulated by ubiquitin", "by ubiquitin ligases", "ligases such", "such as nedd4", "nedd4 wwp2", "wwp2 stub1", "stub1 chip", "xiap mkrn1", "mkrn1 and rnf146", "rnf146 which", "which polyubiquitinate pten", "polyubiquitinate pten in", "pten in response", "in response to", "response to different", "to different stimuli", "different stimuli and", "stimuli and thus", "and thus target", "thus target it", "target it for", "it for proteasome", "for proteasome mediated", "proteasome mediated degradation", "degradation wang", "wang et al.", "et al. 2007", "2007 van", "van themsche et", "themsche et al.", "et al. 2009", "2009 maddika", "maddika et al.", "et al. 2011", "2011 ahmed", "ahmed et al.", "et al. 2012", "2012 lee", "lee et al.", "et al. 2015", "2015 li", "li et al.", "al. 2015 .", "2015 . several", ". several ubiquitin", "several ubiquitin proteases", "proteases such", "such as usp13", "as usp13 and", "usp13 and otud3", "otud3 can", "can remove polyubiquitin", "remove polyubiquitin chains", "polyubiquitin chains from", "chains from pten", "from pten and", "pten and rescue", "and rescue it", "rescue it from", "it from degradation", "degradation zhang", "zhang et al.", "et al. 2013", "2013 yuan", "yuan et al.", "2015 . trim27", "trim27 rfp", "rfp is", "is an e3", "an e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase that", "ligase that polyubiquitinates", "that polyubiquitinates pten", "polyubiquitinates pten on", "pten on multiple", "on multiple lysines", "multiple lysines in", "lysines in the", "in the c2", "the c2 domain", "c2 domain of", "domain of pten", "of pten using", "pten using k27", "using k27 linkage", "k27 linkage between", "linkage between ubiquitin", "between ubiquitin molecules.", "ubiquitin molecules. trim27", "molecules. trim27 mediated", "trim27 mediated ubiquitination", "mediated ubiquitination inhibits", "ubiquitination inhibits pten", "inhibits pten lipid", "pten lipid phosphatase", "lipid phosphatase activity", "activity but", "but does not", "does not affect", "not affect pten", "affect pten protein", "pten protein localization", "protein localization or", "localization or stability", "stability lee", "al. 2013 .
pten", "2013 .
pten phosphorylation", ".
pten phosphorylation by", "phosphorylation by the", "by the tyrosine", "the tyrosine kinase", "tyrosine kinase frk", "frk rak", "rak inhibits", "inhibits nedd4 mediated", "nedd4 mediated polyubiquitination", "mediated polyubiquitination and", "polyubiquitination and subsequent", "and subsequent degradation", "subsequent degradation of", "degradation of pten", "pten thus", "thus increasing pten", "increasing pten half", "pten half life.", "half life. frk", "life. frk mediated", "frk mediated phosphorylation", "mediated phosphorylation also", "phosphorylation also increases", "also increases pten", "increases pten enzymatic", "pten enzymatic activity", "activity yim", "yim et al.", "al. 2009 .", "2009 . casein", ". casein kinase", "casein kinase 2", "2 ck2", "ck2 mediated", "mediated phosphorylation of", "phosphorylation of the", "of the c", "the c terminus", "c terminus of", "terminus of pten", "of pten on", "on multiple serine", "multiple serine and", "serine and threonine", "and threonine residues", "threonine residues increases", "residues increases pten", "increases pten protein", "stability torres", "torres and pulido", "and pulido 2001", "2001 but", "but results in", "results in ~30%", "in ~30% reduction", "~30% reduction in", "reduction in pten", "in pten lipid", "activity miller", "miller et al.", "et al. 2002", "al. 2002 .
prex2", ".
prex2 a", "a rac1 guanine", "rac1 guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factor", "factor gef", "gef can", "can binds to", "binds to pten", "to pten and", "pten and inhibit", "and inhibit its", "inhibit its catalytic", "its catalytic activity", "activity fine", "fine et al.", "pten protein stability is", "protein stability is regulated", "stability is regulated by", "is regulated by ubiquitin", "regulated by ubiquitin ligases", "ubiquitin ligases such", "ligases such as", "as nedd4 wwp2", "chip xiap", "xiap mkrn1 and", "and rnf146 which", "rnf146 which polyubiquitinate", "which polyubiquitinate pten in", "polyubiquitinate pten in response", "pten in response to", "in response to different", "response to different stimuli", "to different stimuli and", "different stimuli and thus", "stimuli and thus target", "and thus target it", "thus target it for", "target it for proteasome", "it for proteasome mediated", "for proteasome mediated degradation", "mediated degradation wang", "degradation wang et", "wang et al. 2007", "al. 2007 van", "2007 van themsche", "van themsche et al.", "themsche et al. 2009", "al. 2009 maddika", "2009 maddika et", "maddika et al. 2011", "al. 2011 ahmed", "2011 ahmed et", "ahmed et al. 2012", "al. 2012 lee", "2012 lee et", "lee et al. 2015", "al. 2015 li", "2015 li et", "li et al. 2015", "et al. 2015 .", "al. 2015 . several", "2015 . several ubiquitin", ". several ubiquitin proteases", "ubiquitin proteases such", "proteases such as", "such as usp13 and", "as usp13 and otud3", "and otud3 can", "otud3 can remove", "can remove polyubiquitin chains", "remove polyubiquitin chains from", "polyubiquitin chains from pten", "chains from pten and", "from pten and rescue", "pten and rescue it", "and rescue it from", "rescue it from degradation", "from degradation zhang", "degradation zhang et", "zhang et al. 2013", "al. 2013 yuan", "2013 yuan et", "yuan et al. 2015", "al. 2015 . trim27", ". trim27 rfp", "rfp is an", "is an e3 ubiquitin", "an e3 ubiquitin ligase", "e3 ubiquitin ligase that", "ubiquitin ligase that polyubiquitinates", "ligase that polyubiquitinates pten", "that polyubiquitinates pten on", "polyubiquitinates pten on multiple", "pten on multiple lysines", "on multiple lysines in", "multiple lysines in the", "lysines in the c2", "in the c2 domain", "the c2 domain of", "c2 domain of pten", "domain of pten using", "of pten using k27", "pten using k27 linkage", "using k27 linkage between", "k27 linkage between ubiquitin", "linkage between ubiquitin molecules.", "between ubiquitin molecules. trim27", "ubiquitin molecules. trim27 mediated", "molecules. trim27 mediated ubiquitination", "trim27 mediated ubiquitination inhibits", "mediated ubiquitination inhibits pten", "ubiquitination inhibits pten lipid", "inhibits pten lipid phosphatase", "pten lipid phosphatase activity", "phosphatase activity but", "activity but does", "but does not affect", "does not affect pten", "not affect pten protein", "affect pten protein localization", "pten protein localization or", "protein localization or stability", "or stability lee", "stability lee et", "lee et al. 2013", "et al. 2013 .
pten", "al. 2013 .
pten phosphorylation", "2013 .
pten phosphorylation by", ".
pten phosphorylation by the", "phosphorylation by the tyrosine", "by the tyrosine kinase", "the tyrosine kinase frk", "kinase frk rak", "rak inhibits nedd4", "inhibits nedd4 mediated polyubiquitination", "nedd4 mediated polyubiquitination and", "mediated polyubiquitination and subsequent", "polyubiquitination and subsequent degradation", "and subsequent degradation of", "subsequent degradation of pten", "of pten thus", "pten thus increasing", "thus increasing pten half", "increasing pten half life.", "pten half life. frk", "half life. frk mediated", "life. frk mediated phosphorylation", "frk mediated phosphorylation also", "mediated phosphorylation also increases", "phosphorylation also increases pten", "also increases pten enzymatic", "increases pten enzymatic activity", "enzymatic activity yim", "activity yim et", "yim et al. 2009", "et al. 2009 .", "al. 2009 . casein", "2009 . casein kinase", ". casein kinase 2", "kinase 2 ck2", "ck2 mediated phosphorylation", "mediated phosphorylation of the", "phosphorylation of the c", "of the c terminus", "the c terminus of", "c terminus of pten", "terminus of pten on", "of pten on multiple", "pten on multiple serine", "on multiple serine and", "multiple serine and threonine", "serine and threonine residues", "and threonine residues increases", "threonine residues increases pten", "residues increases pten protein", "increases pten protein stability", "protein stability torres", "stability torres and", "torres and pulido 2001", "pulido 2001 but", "2001 but results", "but results in ~30%", "results in ~30% reduction", "in ~30% reduction in", "~30% reduction in pten", "reduction in pten lipid", "in pten lipid phosphatase", "phosphatase activity miller", "activity miller et", "miller et al. 2002", "et al. 2002 .
prex2", "2002 .
prex2 a", ".
prex2 a rac1", "a rac1 guanine nucleotide", "rac1 guanine nucleotide exchange", "guanine nucleotide exchange factor", "exchange factor gef", "gef can binds", "can binds to pten", "binds to pten and", "to pten and inhibit", "pten and inhibit its", "and inhibit its catalytic", "inhibit its catalytic activity", "catalytic activity fine", "activity fine et", "fine et al. 2009", "pten protein stability is regulated", "protein stability is regulated by", "stability is regulated by ubiquitin", "is regulated by ubiquitin ligases", "by ubiquitin ligases such", "ubiquitin ligases such as", "ligases such as nedd4", "such as nedd4 wwp2", "nedd4 wwp2 stub1", "wwp2 stub1 chip", "xiap mkrn1 and rnf146", "mkrn1 and rnf146 which", "and rnf146 which polyubiquitinate", "rnf146 which polyubiquitinate pten", "which polyubiquitinate pten in response", "polyubiquitinate pten in response to", "pten in response to different", "in response to different stimuli", "response to different stimuli and", "to different stimuli and thus", "different stimuli and thus target", "stimuli and thus target it", "and thus target it for", "thus target it for proteasome", "target it for proteasome mediated", "it for proteasome mediated degradation", "proteasome mediated degradation wang", "mediated degradation wang et", "degradation wang et al.", "et al. 2007 van", "al. 2007 van themsche", "2007 van themsche et", "van themsche et al. 2009", "et al. 2009 maddika", "al. 2009 maddika et", "2009 maddika et al.", "et al. 2011 ahmed", "al. 2011 ahmed et", "2011 ahmed et al.", "et al. 2012 lee", "al. 2012 lee et", "2012 lee et al.", "et al. 2015 li", "al. 2015 li et", "2015 li et al.", "li et al. 2015 .", "et al. 2015 . several", "al. 2015 . several ubiquitin", "2015 . several ubiquitin proteases", "several ubiquitin proteases such", "ubiquitin proteases such as", "proteases such as usp13", "such as usp13 and otud3", "usp13 and otud3 can", "and otud3 can remove", "otud3 can remove polyubiquitin", "can remove polyubiquitin chains from", "remove polyubiquitin chains from pten", "polyubiquitin chains from pten and", "chains from pten and rescue", "from pten and rescue it", "pten and rescue it from", "and rescue it from degradation", "it from degradation zhang", "from degradation zhang et", "degradation zhang et al.", "et al. 2013 yuan", "al. 2013 yuan et", "2013 yuan et al.", "yuan et al. 2015 .", "et al. 2015 . trim27", "2015 . trim27 rfp", "trim27 rfp is", "rfp is an e3", "is an e3 ubiquitin ligase", "an e3 ubiquitin ligase that", "e3 ubiquitin ligase that polyubiquitinates", "ubiquitin ligase that polyubiquitinates pten", "ligase that polyubiquitinates pten on", "that polyubiquitinates pten on multiple", "polyubiquitinates pten on multiple lysines", "pten on multiple lysines in", "on multiple lysines in the", "multiple lysines in the c2", "lysines in the c2 domain", "in the c2 domain of", "the c2 domain of pten", "c2 domain of pten using", "domain of pten using k27", "of pten using k27 linkage", "pten using k27 linkage between", "using k27 linkage between ubiquitin", "k27 linkage between ubiquitin molecules.", "linkage between ubiquitin molecules. trim27", "between ubiquitin molecules. trim27 mediated", "ubiquitin molecules. trim27 mediated ubiquitination", "molecules. trim27 mediated ubiquitination inhibits", "trim27 mediated ubiquitination inhibits pten", "mediated ubiquitination inhibits pten lipid", "ubiquitination inhibits pten lipid phosphatase", "inhibits pten lipid phosphatase activity", "lipid phosphatase activity but", "phosphatase activity but does", "activity but does not", "but does not affect pten", "does not affect pten protein", "not affect pten protein localization", "affect pten protein localization or", "pten protein localization or stability", "localization or stability lee", "or stability lee et", "stability lee et al.", "lee et al. 2013 .
pten", "et al. 2013 .
pten phosphorylation", "al. 2013 .
pten phosphorylation by", "2013 .
pten phosphorylation by the", ".
pten phosphorylation by the tyrosine", "phosphorylation by the tyrosine kinase", "by the tyrosine kinase frk", "tyrosine kinase frk rak", "frk rak inhibits", "rak inhibits nedd4 mediated", "inhibits nedd4 mediated polyubiquitination and", "nedd4 mediated polyubiquitination and subsequent", "mediated polyubiquitination and subsequent degradation", "polyubiquitination and subsequent degradation of", "and subsequent degradation of pten", "degradation of pten thus", "of pten thus increasing", "pten thus increasing pten", "thus increasing pten half life.", "increasing pten half life. frk", "pten half life. frk mediated", "half life. frk mediated phosphorylation", "life. frk mediated phosphorylation also", "frk mediated phosphorylation also increases", "mediated phosphorylation also increases pten", "phosphorylation also increases pten enzymatic", "also increases pten enzymatic activity", "pten enzymatic activity yim", "enzymatic activity yim et", "activity yim et al.", "yim et al. 2009 .", "et al. 2009 . casein", "al. 2009 . casein kinase", "2009 . casein kinase 2", "casein kinase 2 ck2", "2 ck2 mediated", "ck2 mediated phosphorylation of", "mediated phosphorylation of the c", "phosphorylation of the c terminus", "of the c terminus of", "the c terminus of pten", "c terminus of pten on", "terminus of pten on multiple", "of pten on multiple serine", "pten on multiple serine and", "on multiple serine and threonine", "multiple serine and threonine residues", "serine and threonine residues increases", "and threonine residues increases pten", "threonine residues increases pten protein", "residues increases pten protein stability", "pten protein stability torres", "protein stability torres and", "stability torres and pulido", "and pulido 2001 but", "pulido 2001 but results", "2001 but results in", "but results in ~30% reduction", "results in ~30% reduction in", "in ~30% reduction in pten", "~30% reduction in pten lipid", "reduction in pten lipid phosphatase", "in pten lipid phosphatase activity", "lipid phosphatase activity miller", "phosphatase activity miller et", "activity miller et al.", "miller et al. 2002 .
prex2", "al. 2002 .
prex2 a", "2002 .
prex2 a rac1", ".
prex2 a rac1 guanine", "a rac1 guanine nucleotide exchange", "rac1 guanine nucleotide exchange factor", "nucleotide exchange factor gef", "factor gef can", "gef can binds to", "can binds to pten and", "binds to pten and inhibit", "to pten and inhibit its", "pten and inhibit its catalytic", "and inhibit its catalytic activity", "its catalytic activity fine", "catalytic activity fine et", "activity fine et al.", "fine et al. 2009 ." ] }, { "record_id": "GLY_000594_1_644", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8950505", "r hsa", "hsa 8950505", "r hsa 8950505" ] }, { "record_id": "GLY_000594_1_644", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gene and", "and protein", "protein expression", "expression by", "by jak", "jak stat", "stat signaling", "signaling after", "after interleukin", "interleukin 12", "12 stimulation", "gene and protein", "and protein expression", "protein expression by", "expression by jak", "by jak stat", "jak stat signaling", "stat signaling after", "signaling after interleukin", "after interleukin 12", "interleukin 12 stimulation", "gene and protein expression", "and protein expression by", "protein expression by jak", "expression by jak stat", "by jak stat signaling", "jak stat signaling after", "stat signaling after interleukin", "signaling after interleukin 12", "after interleukin 12 stimulation", "gene and protein expression by", "and protein expression by jak", "protein expression by jak stat", "expression by jak stat signaling", "by jak stat signaling after", "jak stat signaling after interleukin", "stat signaling after interleukin 12", "signaling after interleukin 12 stimulation", "experiments using", "using human", "human cord", "cord blood", "blood cd4", "cd4 +", "t cells", "cells show", "show 22", "22 protein", "protein spots", "spots and", "and 20", "20 protein", "upregulated and", "and downregulated", "downregulated proteins", "proteins respectively", "following interleukin", "rosengren et.al", "2005 .", ". the", "the identified", "identified upregulated", "upregulated proteins", "proteins are:", "ppia and", "pdcd4.
and the", "identified downregulated", "proteins are:
anxa2", "rap1b and", "and gsto1.", "experiments using human", "using human cord", "human cord blood", "cord blood cd4", "blood cd4 +", "+ t", "t cells show", "cells show 22", "show 22 protein", "22 protein spots", "protein spots and", "spots and 20", "and 20 protein", "20 protein spots", "spots upregulated", "upregulated and downregulated", "and downregulated proteins", "downregulated proteins respectively", "respectively following", "following interleukin 12", "stimulation rosengren", "et.al 2005", "2005 . the", ". the identified", "the identified upregulated", "identified upregulated proteins", "upregulated proteins are:", "are: bola2", "bola2 psme2", "mtap ca1", "sod1 ppia", "and pdcd4.
and", "pdcd4.
and the identified", "the identified downregulated", "identified downregulated proteins", "downregulated proteins are:
anxa2", "are:
anxa2 rplp0", "rplp0 capza1", "capza1 sod2", "sod2 snrpa1", "snrpa1 lmnb1", "lmnb1 lcp1", "lcp1 hspa9", "hspa9 serpinb2", "serpinb2 hnrnpf", "hnrnpf taldo1", "taldo1 pak2", "pak2 tcp1", "tcp1 hnrnpa2b1", "hnrnpa2b1 msn", "msn pitpna", "pitpna arf1", "arf1 sod2", "sod2 anxa2", "anxa2 cdc42", "cdc42 rap1b", "rap1b and gsto1.", "experiments using human cord", "using human cord blood", "human cord blood cd4", "cord blood cd4 +", "cd4 + t", "+ t cells", "t cells show 22", "cells show 22 protein", "show 22 protein spots", "22 protein spots and", "protein spots and 20", "spots and 20 protein", "and 20 protein spots", "protein spots upregulated", "spots upregulated and", "upregulated and downregulated proteins", "and downregulated proteins respectively", "proteins respectively following", "respectively following interleukin", "following interleukin 12 stimulation", "12 stimulation rosengren", "stimulation rosengren et.al", "rosengren et.al 2005", "et.al 2005 .", "2005 . the identified", ". the identified upregulated", "the identified upregulated proteins", "identified upregulated proteins are:", "proteins are: bola2", "psme2 mtap", "ca1 gsta2", "gsta2 rala", "rala cnn2", "cnn2 cfl1", "cfl1 tcp1", "tcp1 hnrnpdl", "hnrnpdl mif", "mif aip", "aip sod1", "sod1 ppia and", "ppia and pdcd4.
and", "and pdcd4.
and the", "pdcd4.
and the identified downregulated", "the identified downregulated proteins", "identified downregulated proteins are:
anxa2", "proteins are:
anxa2 rplp0", "cdc42 rap1b and", "experiments using human cord blood", "using human cord blood cd4", "human cord blood cd4 +", "blood cd4 + t", "cd4 + t cells", "+ t cells show", "t cells show 22 protein", "cells show 22 protein spots", "show 22 protein spots and", "22 protein spots and 20", "protein spots and 20 protein", "spots and 20 protein spots", "20 protein spots upregulated", "protein spots upregulated and", "spots upregulated and downregulated", "upregulated and downregulated proteins respectively", "downregulated proteins respectively following", "proteins respectively following interleukin", "respectively following interleukin 12", "interleukin 12 stimulation rosengren", "12 stimulation rosengren et.al", "rosengren et.al 2005 .", "et.al 2005 . the", "2005 . the identified upregulated", ". the identified upregulated proteins", "the identified upregulated proteins are:", "upregulated proteins are: bola2", "are: bola2 psme2", "ppia and pdcd4.
and the", "and pdcd4.
and the identified", "pdcd4.
and the identified downregulated proteins", "the identified downregulated proteins are:
anxa2", "downregulated proteins are:
anxa2 rplp0", "are:
anxa2 rplp0 capza1", "rplp0 capza1 sod2", "capza1 sod2 snrpa1", "sod2 snrpa1 lmnb1", "snrpa1 lmnb1 lcp1", "lmnb1 lcp1 hspa9", "lcp1 hspa9 serpinb2", "hspa9 serpinb2 hnrnpf", "serpinb2 hnrnpf taldo1", "hnrnpf taldo1 pak2", "taldo1 pak2 tcp1", "pak2 tcp1 hnrnpa2b1", "tcp1 hnrnpa2b1 msn", "hnrnpa2b1 msn pitpna", "msn pitpna arf1", "pitpna arf1 sod2", "arf1 sod2 anxa2", "sod2 anxa2 cdc42", "anxa2 cdc42 rap1b", "cdc42 rap1b and gsto1." ] }, { "record_id": "GLY_000594_1_645", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8951664", "r hsa", "hsa 8951664", "r hsa 8951664" ] }, { "record_id": "GLY_000594_1_645", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nedd8 is", "is a", "a small", "small ubiquitin", "ubiquitin like", "like molecule", "molecule that", "that is", "is conjugated", "conjugated to", "to substrate", "substrate proteins", "proteins through", "through an", "an e1", "e1 to", "to e3", "e3 enzyme", "enzyme cascade", "cascade similar", "similar to", "to that", "that for", "for ubiquitin.", "ubiquitin. the", "the best", "best characterized", "characterized target", "target of", "of neddylation", "neddylation is", "is the", "the cullin", "cullin scaffold", "scaffold subunit", "subunit of", "of cullin", "cullin ring", "ring e3", "e3 ubiquitin", "ubiquitin ligases", "which themselves", "themselves target", "target numerous", "numerous cellular", "cellular proteins", "proteins for", "for degradation", "degradation by", "by the", "the proteasome", "hori et", "et al", "reviewed in", "in soucy", "soucy et", "lyedeard et", "2013 .", ". the", "the multisubunit", "multisubunit crl", "crl complexes", "complexes are", "are compositionally", "compositionally diverse", "but each", "each contains", "contains a", "a scaffolding", "scaffolding cullin", "cullin protein", "7 or", "or 9", "and a", "a ring", "ring box", "box containing", "containing e3", "e3 ligase", "ligase subunit", "subunit rbx", "along with", "with other", "other adaptor", "adaptor and", "and substrate", "substrate interacting", "interacting subunits.", "subunits. rbx2", "also known", "known as", "as rnf7", "interacts preferentially", "preferentially with", "with cul5", "while rbx1", "rbx1 is", "the primary", "primary e3", "e3 for", "for most", "most other", "other cullin", "cullin family", "family members", "in mahon", "mahon et", "2014 .", ". neddylation", "neddylation of", "of the", "cullin subunit", "subunit increases", "increases the", "the ubiquitination", "ubiquitination activity", "activity of", "the crl", "crl complex", "podust et", "read et", "wu et", "kawakami et", "ohh et", "yu et", "2015 .", ". in", "in addition", "addition to", "to crl", "a number", "number of", "of other", "other less", "less well", "well characterized", "characterized nedd8", "nedd8 targets", "targets have", "have been", "been identified.", "identified. these", "these include", "include other", "other e3", "ligases such", "such as", "as smurf1", "smurf1 and", "and mdm2", "receptor tyrosine", "tyrosine kinases", "kinases such", "as egfr", "egfr and", "and tgf", "tgf beta", "beta rii", "and proteins", "proteins that", "that contribute", "contribute to", "to transcriptional", "transcriptional regulation", "among others", "xie et", "watson et", "oved et", "zuo et", "xirodimas et", "singh et", "abida et", "liu et", "al 2010", "loftus et", "aoki et", "in enchev", "enchev et", ".
like", "
like ubiquitin", "nedd8 undergoes", "undergoes post", "post translational", "translational processing", "processing to", "to generate", "generate the", "the mature", "mature form.", "form. uchl3", "or senp8", "senp8 mediated", "mediated proteolysis", "proteolysis removes", "removes the", "the c", "c terminal", "terminal 5", "5 amino", "amino acids", "acids of", "of nedd8", "generating a", "a novel", "novel c", "terminal glycine", "glycine residue", "residue for", "for conjugation", "conjugation to", "to the", "the cysteine", "cysteine residues", "residues in", "in the", "the e1", "e2 enzymes", "enzymes or", "or lysine", "lysine residues", "the substrate", "substrate protein", "usually the", "the e3", "e3 nedd8", "nedd8 ligase", "ligase itself", "wada et", ". most", "most substrates", "substrates in", "in vivo", "vivo appear", "appear to", "to be", "be singly", "singly neddylated", "neddylated on", "on one", "one or", "or more", "more lysine", "but nedd8", "nedd8 chains", "chains have", "been formed", "formed on", "on cullin", "cullin substrates", "in vitro", "vitro and", "and on", "on histone", "histone h4", "h4 in", "in cultured", "cultured human", "human cells", "cells after", "after dna", "dna damage", "jones et", "ohki et", "jeram et", "ma et", "the significance", "significance of", "chains is", "is still", "still not", "not clear.", "clear.
nedd8", "
nedd8 has", "has a", "a single", "single heterodimeric", "heterodimeric e1", "e1 enzyme", "consisting of", "of nae1", "as appbp1", "and uba3", "and two", "two e2", "ube2m and", "and ube2f", "which are", "are n", "n terminally", "terminally acetylated", "walden et", "bohnsack et", "huang et", "scott et", "monda et", ". all", "all nedd8", "nedd8 e3", "e3 enzymes", "enzymes reported", "reported to", "to date", "date also", "also function", "function as", "as e3", "and most", "most belong", "belong to", "the ring", "ring domain", "domain class.", "class. the", "enzymes are", "are the", "complexes described", "described above.", "above. rbx1", "rbx1 containing", "containing complexes", "complexes interact", "interact preferentially", "with ube2m", "while ube2f", "ube2f is", "the e2", "e2 for", "for rbx2", "rbx2 containing", ".
neddylation", "
neddylation is", "is regulated", "regulated in", "vivo by", "by interaction", "interaction with", "with dcun1d", "dcun1d proteins", "also called", "called dcnls", "dcnls .", "the 5", "5 human", "human dcun1d", "proteins interact", "interact both", "both with", "with cullins", "cullins and", "and with", "with the", "the nedd8", "nedd8 e2", "e2 proteins", "proteins and", "and thereby", "thereby increase", "increase the", "the kinetic", "kinetic efficiency", "efficiency of", "kurz et", ". glomulin", "is another", "another regulator", "regulator of", "of crl", "crl function", "function that", "that binds", "binds to", "the neddylated", "neddylated cullin", "cullin and", "and competitively", "competitively inhibits", "inhibits interaction", "the ubiquitin", "ubiquitin e2", "e2 enzyme", "arai et", "tron et", "duda et", "2014 .
the", ".
the multisubunit", "multisubunit cop9", "cop9 signalosome", "signalosome is", "the only", "only cullin", "cullin deneddylase", "while senp8", "as den1", "contributes to", "to deneddylation", "deneddylation of", "other non", "non cullin", "cullin nedd8", "cope et", "emberley et", "chan et", "in wei", "wei et", "the deneddylated", "deneddylated state", "cullins bind", "bind to", "to cand1", "cullin associated", "associated nedd8", "nedd8 dissociated", "dissociated protein1", "which displaces", "displaces the", "the cop9", "signalosome and", "and promotes", "promotes the", "the exchange", "exchange of", "ubiquitin substrate", "substrate specific", "specific adaptor.", "adaptor. this", "this allows", "allows crl", "complexes to", "be reconfigured", "reconfigured to", "to target", "target other", "other subtrates", "subtrates for", "for ubiquitination", "schmidt et", "pierce et", "2014 .

", "nedd8 is a", "is a small", "a small ubiquitin", "small ubiquitin like", "ubiquitin like molecule", "like molecule that", "molecule that is", "that is conjugated", "is conjugated to", "conjugated to substrate", "to substrate proteins", "substrate proteins through", "proteins through an", "through an e1", "an e1 to", "e1 to e3", "to e3 enzyme", "e3 enzyme cascade", "enzyme cascade similar", "cascade similar to", "similar to that", "to that for", "that for ubiquitin.", "for ubiquitin. the", "ubiquitin. the best", "the best characterized", "best characterized target", "characterized target of", "target of neddylation", "of neddylation is", "neddylation is the", "is the cullin", "the cullin scaffold", "cullin scaffold subunit", "scaffold subunit of", "subunit of cullin", "of cullin ring", "cullin ring e3", "ring e3 ubiquitin", "e3 ubiquitin ligases", "ligases crls", "which themselves target", "themselves target numerous", "target numerous cellular", "numerous cellular proteins", "cellular proteins for", "proteins for degradation", "for degradation by", "degradation by the", "by the proteasome", "proteasome hori", "hori et al", "al 1999", "1999 reviewed", "reviewed in soucy", "in soucy et", "soucy et al", "2010 lyedeard", "lyedeard et al", "al 2013", "2013 . the", ". the multisubunit", "the multisubunit crl", "multisubunit crl complexes", "crl complexes are", "complexes are compositionally", "are compositionally diverse", "diverse but", "but each contains", "each contains a", "contains a scaffolding", "a scaffolding cullin", "scaffolding cullin protein", "protein cul1", "cul1 2", "2 3", "3 4a", "4a 4b", "4b 5", "5 7", "7 or 9", "9 and", "and a ring", "a ring box", "ring box containing", "box containing e3", "containing e3 ligase", "e3 ligase subunit", "ligase subunit rbx", "rbx along", "along with other", "with other adaptor", "other adaptor and", "adaptor and substrate", "and substrate interacting", "substrate interacting subunits.", "interacting subunits. rbx2", "rbx2 also", "also known as", "known as rnf7", "rnf7 interacts", "interacts preferentially with", "preferentially with cul5", "cul5 while", "while rbx1 is", "rbx1 is the", "is the primary", "the primary e3", "primary e3 for", "e3 for most", "for most other", "most other cullin", "other cullin family", "cullin family members", "members reviewed", "reviewed in mahon", "in mahon et", "mahon et al", "al 2014", "2014 . neddylation", ". neddylation of", "neddylation of the", "of the cullin", "the cullin subunit", "cullin subunit increases", "subunit increases the", "increases the ubiquitination", "the ubiquitination activity", "ubiquitination activity of", "activity of the", "of the crl", "the crl complex", "complex podust", "podust et al", "al 2000", "2000 read", "read et al", "2000 wu", "wu et al", "2000 kawakami", "kawakami et al", "al 2001", "2001 ohh", "ohh et al", "al 2002", "2002 yu", "yu et al", "al 2015", "2015 . in", ". in addition", "in addition to", "addition to crl", "to crl complexes", "complexes a", "a number of", "number of other", "of other less", "other less well", "less well characterized", "well characterized nedd8", "characterized nedd8 targets", "nedd8 targets have", "targets have been", "have been identified.", "been identified. these", "identified. these include", "these include other", "include other e3", "other e3 ubiquitin", "ubiquitin ligases such", "ligases such as", "such as smurf1", "as smurf1 and", "smurf1 and mdm2", "mdm2 receptor", "receptor tyrosine kinases", "tyrosine kinases such", "kinases such as", "such as egfr", "as egfr and", "egfr and tgf", "and tgf beta", "tgf beta rii", "rii and", "and proteins that", "proteins that contribute", "that contribute to", "contribute to transcriptional", "to transcriptional regulation", "regulation among", "others xie", "xie et al", "2014 watson", "watson et al", "2010 oved", "oved et al", "al 2006", "2006 zuo", "zuo et al", "2013 xirodimas", "xirodimas et al", "al 2004", "2004 singh", "singh et al", "al 2007", "2007 abida", "abida et al", "2007 liu", "liu et al", "et al 2010", "2010 watson", "2006 loftus", "loftus et al", "al 2012", "2012 aoki", "aoki et al", "2013 reviewed", "reviewed in enchev", "in enchev et", "enchev et al", "2015 .
like", ".
like ubiquitin", "ubiquitin nedd8", "nedd8 undergoes post", "undergoes post translational", "post translational processing", "translational processing to", "processing to generate", "to generate the", "generate the mature", "the mature form.", "mature form. uchl3", "uchl3 or", "or senp8 mediated", "senp8 mediated proteolysis", "mediated proteolysis removes", "proteolysis removes the", "removes the c", "the c terminal", "c terminal 5", "terminal 5 amino", "5 amino acids", "amino acids of", "acids of nedd8", "nedd8 generating", "generating a novel", "a novel c", "novel c terminal", "c terminal glycine", "terminal glycine residue", "glycine residue for", "residue for conjugation", "for conjugation to", "conjugation to the", "to the cysteine", "the cysteine residues", "cysteine residues in", "residues in the", "in the e1", "e1 e2", "e2 enzymes or", "enzymes or lysine", "or lysine residues", "lysine residues in", "in the substrate", "the substrate protein", "protein usually", "usually the e3", "the e3 nedd8", "e3 nedd8 ligase", "nedd8 ligase itself", "itself wada", "wada et al", "al 1998", "1998 reviewed", "2015 . most", ". most substrates", "most substrates in", "substrates in vivo", "in vivo appear", "vivo appear to", "appear to be", "to be singly", "be singly neddylated", "singly neddylated on", "neddylated on one", "on one or", "one or more", "or more lysine", "more lysine residues", "residues but", "but nedd8 chains", "nedd8 chains have", "chains have been", "have been formed", "been formed on", "formed on cullin", "on cullin substrates", "cullin substrates in", "substrates in vitro", "in vitro and", "vitro and on", "and on histone", "on histone h4", "histone h4 in", "h4 in cultured", "in cultured human", "cultured human cells", "human cells after", "cells after dna", "after dna damage", "damage jones", "jones et al", "al 2008", "2008 ohki", "ohki et al", "al 2009", "2009 xirodimas", "2008 jeram", "jeram et al", "2010 ma", "ma et al", "2015 . the", ". the significance", "the significance of", "significance of nedd8", "of nedd8 chains", "nedd8 chains is", "chains is still", "is still not", "still not clear.", "not clear.
nedd8", "clear.
nedd8 has", "
nedd8 has a", "has a single", "a single heterodimeric", "single heterodimeric e1", "heterodimeric e1 enzyme", "enzyme consisting", "consisting of nae1", "nae1 also", "known as appbp1", "appbp1 and", "uba3 and", "and two e2", "two e2 enzymes", "enzymes ube2m", "ube2m and ube2f", "ube2f which", "which are n", "are n terminally", "n terminally acetylated", "acetylated walden", "walden et al", "al 2003", "2003 bohnsack", "bohnsack et al", "2003 huang", "huang et al", "2004 huang", "al 2005", "2005 huang", "2009 scott", "scott et al", "al 2011a", "2011a monda", "monda et al", "2015 . all", ". all nedd8", "all nedd8 e3", "nedd8 e3 enzymes", "e3 enzymes reported", "enzymes reported to", "reported to date", "to date also", "date also function", "also function as", "function as e3", "as e3 ubiquitin", "ligases and", "and most belong", "most belong to", "belong to the", "to the ring", "the ring domain", "ring domain class.", "domain class. the", "class. the best", "best characterized nedd8", "characterized nedd8 e3", "e3 enzymes are", "enzymes are the", "are the crl", "the crl complexes", "crl complexes described", "complexes described above.", "described above. rbx1", "above. rbx1 containing", "rbx1 containing complexes", "containing complexes interact", "complexes interact preferentially", "interact preferentially with", "preferentially with ube2m", "ube2m while", "while ube2f is", "ube2f is the", "is the e2", "the e2 for", "e2 for rbx2", "for rbx2 containing", "rbx2 containing complexes", "complexes huang", "2009 monda", "2013 .
neddylation", ".
neddylation is", "
neddylation is regulated", "is regulated in", "regulated in vivo", "in vivo by", "vivo by interaction", "by interaction with", "interaction with dcun1d", "with dcun1d proteins", "proteins also", "also called dcnls", "called dcnls .", "dcnls . the", ". the 5", "the 5 human", "5 human dcun1d", "human dcun1d proteins", "dcun1d proteins interact", "proteins interact both", "interact both with", "both with cullins", "with cullins and", "cullins and with", "and with the", "with the nedd8", "the nedd8 e2", "nedd8 e2 proteins", "e2 proteins and", "proteins and thereby", "and thereby increase", "thereby increase the", "increase the kinetic", "the kinetic efficiency", "kinetic efficiency of", "efficiency of neddylation", "neddylation kurz", "kurz et al", "2005 kurz", "2008 scott", "2010 scott", "2011a scott", "2014 monda", "2013 . glomulin", "glomulin glmn", "glmn is", "is another regulator", "another regulator of", "regulator of crl", "of crl function", "crl function that", "function that binds", "that binds to", "binds to the", "to the neddylated", "the neddylated cullin", "neddylated cullin and", "cullin and competitively", "and competitively inhibits", "competitively inhibits interaction", "inhibits interaction with", "interaction with the", "with the ubiquitin", "the ubiquitin e2", "ubiquitin e2 enzyme", "enzyme arai", "arai et al", "2003 tron", "tron et al", "2012 duda", "duda et al", "2012 reviewed", "2014 .
the multisubunit", ".
the multisubunit cop9", "multisubunit cop9 signalosome", "cop9 signalosome is", "signalosome is the", "is the only", "the only cullin", "only cullin deneddylase", "deneddylase while", "senp8 also", "known as den1", "den1 contributes", "contributes to deneddylation", "to deneddylation of", "deneddylation of other", "of other non", "other non cullin", "non cullin nedd8", "cullin nedd8 targets", "targets cope", "cope et al", "2002 emberley", "emberley et al", "2012 chan", "chan et al", "2008 wu", "2003 reviewed", "reviewed in wei", "in wei et", "wei et al", "2008 enchev", ". in the", "in the deneddylated", "the deneddylated state", "state cullins", "cullins bind to", "bind to cand1", "cand1 cullin", "cullin associated nedd8", "associated nedd8 dissociated", "nedd8 dissociated protein1", "which displaces the", "displaces the cop9", "the cop9 signalosome", "cop9 signalosome and", "signalosome and promotes", "and promotes the", "promotes the exchange", "the exchange of", "exchange of the", "of the ubiquitin", "the ubiquitin substrate", "ubiquitin substrate specific", "substrate specific adaptor.", "specific adaptor. this", "adaptor. this allows", "this allows crl", "allows crl complexes", "crl complexes to", "complexes to be", "to be reconfigured", "be reconfigured to", "reconfigured to target", "to target other", "target other subtrates", "other subtrates for", "subtrates for ubiquitination", "ubiquitination liu", "2002 schmidt", "schmidt et al", "2009 pierce", "pierce et al", "nedd8 is a small", "is a small ubiquitin", "a small ubiquitin like", "small ubiquitin like molecule", "ubiquitin like molecule that", "like molecule that is", "molecule that is conjugated", "that is conjugated to", "is conjugated to substrate", "conjugated to substrate proteins", "to substrate proteins through", "substrate proteins through an", "proteins through an e1", "through an e1 to", "an e1 to e3", "e1 to e3 enzyme", "to e3 enzyme cascade", "e3 enzyme cascade similar", "enzyme cascade similar to", "cascade similar to that", "similar to that for", "to that for ubiquitin.", "that for ubiquitin. the", "for ubiquitin. the best", "ubiquitin. the best characterized", "the best characterized target", "best characterized target of", "characterized target of neddylation", "target of neddylation is", "of neddylation is the", "neddylation is the cullin", "is the cullin scaffold", "the cullin scaffold subunit", "cullin scaffold subunit of", "scaffold subunit of cullin", "subunit of cullin ring", "of cullin ring e3", "cullin ring e3 ubiquitin", "ring e3 ubiquitin ligases", "ubiquitin ligases crls", "crls which", "which themselves target numerous", "themselves target numerous cellular", "target numerous cellular proteins", "numerous cellular proteins for", "cellular proteins for degradation", "proteins for degradation by", "for degradation by the", "degradation by the proteasome", "the proteasome hori", "proteasome hori et", "et al 1999", "1999 reviewed in", "reviewed in soucy et", "in soucy et al", "2010 lyedeard et", "et al 2013", "al 2013 .", "2013 . the multisubunit", ". the multisubunit crl", "the multisubunit crl complexes", "multisubunit crl complexes are", "crl complexes are compositionally", "complexes are compositionally diverse", "compositionally diverse but", "diverse but each", "but each contains a", "each contains a scaffolding", "contains a scaffolding cullin", "a scaffolding cullin protein", "cullin protein cul1", "5 7 or", "or 9 and", "9 and a", "and a ring box", "a ring box containing", "ring box containing e3", "box containing e3 ligase", "containing e3 ligase subunit", "e3 ligase subunit rbx", "subunit rbx along", "rbx along with", "along with other adaptor", "with other adaptor and", "other adaptor and substrate", "adaptor and substrate interacting", "and substrate interacting subunits.", "substrate interacting subunits. rbx2", "subunits. rbx2 also", "rbx2 also known", "also known as rnf7", "as rnf7 interacts", "rnf7 interacts preferentially", "interacts preferentially with cul5", "with cul5 while", "cul5 while rbx1", "while rbx1 is the", "rbx1 is the primary", "is the primary e3", "the primary e3 for", "primary e3 for most", "e3 for most other", "for most other cullin", "most other cullin family", "other cullin family members", "family members reviewed", "members reviewed in", "reviewed in mahon et", "in mahon et al", "et al 2014", "al 2014 .", "2014 . neddylation of", ". neddylation of the", "neddylation of the cullin", "of the cullin subunit", "the cullin subunit increases", "cullin subunit increases the", "subunit increases the ubiquitination", "increases the ubiquitination activity", "the ubiquitination activity of", "ubiquitination activity of the", "activity of the crl", "of the crl complex", "crl complex podust", "complex podust et", "et al 2000", "2000 read et", "2000 wu et", "2000 kawakami et", "et al 2001", "2001 ohh et", "et al 2002", "2002 yu et", "et al 2015", "al 2015 .", "2015 . in addition", ". in addition to", "in addition to crl", "addition to crl complexes", "crl complexes a", "complexes a number", "a number of other", "number of other less", "of other less well", "other less well characterized", "less well characterized nedd8", "well characterized nedd8 targets", "characterized nedd8 targets have", "nedd8 targets have been", "targets have been identified.", "have been identified. these", "been identified. these include", "identified. these include other", "these include other e3", "include other e3 ubiquitin", "other e3 ubiquitin ligases", "e3 ubiquitin ligases such", "ubiquitin ligases such as", "ligases such as smurf1", "such as smurf1 and", "as smurf1 and mdm2", "and mdm2 receptor", "mdm2 receptor tyrosine", "receptor tyrosine kinases such", "tyrosine kinases such as", "kinases such as egfr", "such as egfr and", "as egfr and tgf", "egfr and tgf beta", "and tgf beta rii", "beta rii and", "rii and proteins", "and proteins that contribute", "proteins that contribute to", "that contribute to transcriptional", "contribute to transcriptional regulation", "transcriptional regulation among", "regulation among others", "among others xie", "others xie et", "2014 watson et", "2010 oved et", "et al 2006", "2006 zuo et", "2013 xirodimas et", "et al 2004", "2004 singh et", "et al 2007", "2007 abida et", "2007 liu et", "liu et al 2010", "al 2010 watson", "2010 watson et", "2006 loftus et", "et al 2012", "2012 aoki et", "2013 reviewed in", "reviewed in enchev et", "in enchev et al", "2015 .
like ubiquitin", "
like ubiquitin nedd8", "ubiquitin nedd8 undergoes", "nedd8 undergoes post translational", "undergoes post translational processing", "post translational processing to", "translational processing to generate", "processing to generate the", "to generate the mature", "generate the mature form.", "the mature form. uchl3", "form. uchl3 or", "uchl3 or senp8", "or senp8 mediated proteolysis", "senp8 mediated proteolysis removes", "mediated proteolysis removes the", "proteolysis removes the c", "removes the c terminal", "the c terminal 5", "c terminal 5 amino", "terminal 5 amino acids", "5 amino acids of", "amino acids of nedd8", "of nedd8 generating", "nedd8 generating a", "generating a novel c", "a novel c terminal", "novel c terminal glycine", "c terminal glycine residue", "terminal glycine residue for", "glycine residue for conjugation", "residue for conjugation to", "for conjugation to the", "conjugation to the cysteine", "to the cysteine residues", "the cysteine residues in", "cysteine residues in the", "residues in the e1", "the e1 e2", "e1 e2 enzymes", "e2 enzymes or lysine", "enzymes or lysine residues", "or lysine residues in", "lysine residues in the", "residues in the substrate", "in the substrate protein", "substrate protein usually", "protein usually the", "usually the e3 nedd8", "the e3 nedd8 ligase", "e3 nedd8 ligase itself", "ligase itself wada", "itself wada et", "et al 1998", "1998 reviewed in", "2015 . most substrates", ". most substrates in", "most substrates in vivo", "substrates in vivo appear", "in vivo appear to", "vivo appear to be", "appear to be singly", "to be singly neddylated", "be singly neddylated on", "singly neddylated on one", "neddylated on one or", "on one or more", "one or more lysine", "or more lysine residues", "lysine residues but", "residues but nedd8", "but nedd8 chains have", "nedd8 chains have been", "chains have been formed", "have been formed on", "been formed on cullin", "formed on cullin substrates", "on cullin substrates in", "cullin substrates in vitro", "substrates in vitro and", "in vitro and on", "vitro and on histone", "and on histone h4", "on histone h4 in", "histone h4 in cultured", "h4 in cultured human", "in cultured human cells", "cultured human cells after", "human cells after dna", "cells after dna damage", "dna damage jones", "damage jones et", "et al 2008", "2008 ohki et", "et al 2009", "2009 xirodimas et", "2008 jeram et", "2010 ma et", "2015 . the significance", ". the significance of", "the significance of nedd8", "significance of nedd8 chains", "of nedd8 chains is", "nedd8 chains is still", "chains is still not", "is still not clear.", "still not clear.
nedd8", "not clear.
nedd8 has", "clear.
nedd8 has a", "
nedd8 has a single", "has a single heterodimeric", "a single heterodimeric e1", "single heterodimeric e1 enzyme", "e1 enzyme consisting", "enzyme consisting of", "of nae1 also", "nae1 also known", "also known as appbp1", "as appbp1 and", "appbp1 and uba3", "and uba3 and", "uba3 and two", "and two e2 enzymes", "e2 enzymes ube2m", "enzymes ube2m and", "and ube2f which", "ube2f which are", "which are n terminally", "are n terminally acetylated", "terminally acetylated walden", "acetylated walden et", "et al 2003", "2003 bohnsack et", "2003 huang et", "2004 huang et", "et al 2005", "2005 huang et", "2009 scott et", "et al 2011a", "2011a monda et", "2015 . all nedd8", ". all nedd8 e3", "all nedd8 e3 enzymes", "nedd8 e3 enzymes reported", "e3 enzymes reported to", "enzymes reported to date", "reported to date also", "to date also function", "date also function as", "also function as e3", "function as e3 ubiquitin", "as e3 ubiquitin ligases", "ubiquitin ligases and", "ligases and most", "and most belong to", "most belong to the", "belong to the ring", "to the ring domain", "the ring domain class.", "ring domain class. the", "domain class. the best", "class. the best characterized", "the best characterized nedd8", "best characterized nedd8 e3", "characterized nedd8 e3 enzymes", "nedd8 e3 enzymes are", "e3 enzymes are the", "enzymes are the crl", "are the crl complexes", "the crl complexes described", "crl complexes described above.", "complexes described above. rbx1", "described above. rbx1 containing", "above. rbx1 containing complexes", "rbx1 containing complexes interact", "containing complexes interact preferentially", "complexes interact preferentially with", "interact preferentially with ube2m", "with ube2m while", "ube2m while ube2f", "while ube2f is the", "ube2f is the e2", "is the e2 for", "the e2 for rbx2", "e2 for rbx2 containing", "for rbx2 containing complexes", "containing complexes huang", "complexes huang et", "2009 monda et", "2013 .
neddylation is", ".
neddylation is regulated", "
neddylation is regulated in", "is regulated in vivo", "regulated in vivo by", "in vivo by interaction", "vivo by interaction with", "by interaction with dcun1d", "interaction with dcun1d proteins", "dcun1d proteins also", "proteins also called", "also called dcnls .", "called dcnls . the", "dcnls . the 5", ". the 5 human", "the 5 human dcun1d", "5 human dcun1d proteins", "human dcun1d proteins interact", "dcun1d proteins interact both", "proteins interact both with", "interact both with cullins", "both with cullins and", "with cullins and with", "cullins and with the", "and with the nedd8", "with the nedd8 e2", "the nedd8 e2 proteins", "nedd8 e2 proteins and", "e2 proteins and thereby", "proteins and thereby increase", "and thereby increase the", "thereby increase the kinetic", "increase the kinetic efficiency", "the kinetic efficiency of", "kinetic efficiency of neddylation", "of neddylation kurz", "neddylation kurz et", "2005 kurz et", "2008 scott et", "2010 scott et", "2011a scott et", "2014 monda et", ". glomulin glmn", "glmn is another", "is another regulator of", "another regulator of crl", "regulator of crl function", "of crl function that", "crl function that binds", "function that binds to", "that binds to the", "binds to the neddylated", "to the neddylated cullin", "the neddylated cullin and", "neddylated cullin and competitively", "cullin and competitively inhibits", "and competitively inhibits interaction", "competitively inhibits interaction with", "inhibits interaction with the", "interaction with the ubiquitin", "with the ubiquitin e2", "the ubiquitin e2 enzyme", "e2 enzyme arai", "enzyme arai et", "2003 tron et", "2012 duda et", "2012 reviewed in", "al 2014 .
the", "2014 .
the multisubunit cop9", ".
the multisubunit cop9 signalosome", "multisubunit cop9 signalosome is", "cop9 signalosome is the", "signalosome is the only", "is the only cullin", "the only cullin deneddylase", "cullin deneddylase while", "deneddylase while senp8", "while senp8 also", "senp8 also known", "also known as den1", "as den1 contributes", "den1 contributes to", "contributes to deneddylation of", "to deneddylation of other", "deneddylation of other non", "of other non cullin", "other non cullin nedd8", "non cullin nedd8 targets", "nedd8 targets cope", "targets cope et", "2002 emberley et", "2012 chan et", "2008 wu et", "2003 reviewed in", "reviewed in wei et", "in wei et al", "2008 enchev et", "2015 . in the", ". in the deneddylated", "in the deneddylated state", "deneddylated state cullins", "state cullins bind", "cullins bind to cand1", "to cand1 cullin", "cand1 cullin associated", "cullin associated nedd8 dissociated", "associated nedd8 dissociated protein1", "protein1 which", "which displaces the cop9", "displaces the cop9 signalosome", "the cop9 signalosome and", "cop9 signalosome and promotes", "signalosome and promotes the", "and promotes the exchange", "promotes the exchange of", "the exchange of the", "exchange of the ubiquitin", "of the ubiquitin substrate", "the ubiquitin substrate specific", "ubiquitin substrate specific adaptor.", "substrate specific adaptor. this", "specific adaptor. this allows", "adaptor. this allows crl", "this allows crl complexes", "allows crl complexes to", "crl complexes to be", "complexes to be reconfigured", "to be reconfigured to", "be reconfigured to target", "reconfigured to target other", "to target other subtrates", "target other subtrates for", "other subtrates for ubiquitination", "for ubiquitination liu", "ubiquitination liu et", "2002 schmidt et", "2009 pierce et", "al 2014 .

", "nedd8 is a small ubiquitin", "is a small ubiquitin like", "a small ubiquitin like molecule", "small ubiquitin like molecule that", "ubiquitin like molecule that is", "like molecule that is conjugated", "molecule that is conjugated to", "that is conjugated to substrate", "is conjugated to substrate proteins", "conjugated to substrate proteins through", "to substrate proteins through an", "substrate proteins through an e1", "proteins through an e1 to", "through an e1 to e3", "an e1 to e3 enzyme", "e1 to e3 enzyme cascade", "to e3 enzyme cascade similar", "e3 enzyme cascade similar to", "enzyme cascade similar to that", "cascade similar to that for", "similar to that for ubiquitin.", "to that for ubiquitin. the", "that for ubiquitin. the best", "for ubiquitin. the best characterized", "ubiquitin. the best characterized target", "the best characterized target of", "best characterized target of neddylation", "characterized target of neddylation is", "target of neddylation is the", "of neddylation is the cullin", "neddylation is the cullin scaffold", "is the cullin scaffold subunit", "the cullin scaffold subunit of", "cullin scaffold subunit of cullin", "scaffold subunit of cullin ring", "subunit of cullin ring e3", "of cullin ring e3 ubiquitin", "cullin ring e3 ubiquitin ligases", "e3 ubiquitin ligases crls", "crls which themselves", "which themselves target numerous cellular", "themselves target numerous cellular proteins", "target numerous cellular proteins for", "numerous cellular proteins for degradation", "cellular proteins for degradation by", "proteins for degradation by the", "for degradation by the proteasome", "by the proteasome hori", "the proteasome hori et", "proteasome hori et al", "hori et al 1999", "al 1999 reviewed", "1999 reviewed in soucy", "reviewed in soucy et al", "soucy et al 2010", "al 2010 lyedeard", "2010 lyedeard et al", "lyedeard et al 2013", "et al 2013 .", "al 2013 . the", "2013 . the multisubunit crl", ". the multisubunit crl complexes", "the multisubunit crl complexes are", "multisubunit crl complexes are compositionally", "crl complexes are compositionally diverse", "are compositionally diverse but", "compositionally diverse but each", "diverse but each contains", "but each contains a scaffolding", "each contains a scaffolding cullin", "contains a scaffolding cullin protein", "scaffolding cullin protein cul1", "protein cul1 2", "cul1 2 3", "2 3 4a", "3 4a 4b", "4a 4b 5", "4b 5 7", "5 7 or 9", "7 or 9 and", "or 9 and a", "9 and a ring", "and a ring box containing", "a ring box containing e3", "ring box containing e3 ligase", "box containing e3 ligase subunit", "containing e3 ligase subunit rbx", "ligase subunit rbx along", "subunit rbx along with", "rbx along with other", "along with other adaptor and", "with other adaptor and substrate", "other adaptor and substrate interacting", "adaptor and substrate interacting subunits.", "and substrate interacting subunits. rbx2", "interacting subunits. rbx2 also", "subunits. rbx2 also known", "rbx2 also known as", "known as rnf7 interacts", "as rnf7 interacts preferentially", "rnf7 interacts preferentially with", "preferentially with cul5 while", "with cul5 while rbx1", "cul5 while rbx1 is", "while rbx1 is the primary", "rbx1 is the primary e3", "is the primary e3 for", "the primary e3 for most", "primary e3 for most other", "e3 for most other cullin", "for most other cullin family", "most other cullin family members", "cullin family members reviewed", "family members reviewed in", "members reviewed in mahon", "reviewed in mahon et al", "mahon et al 2014", "et al 2014 .", "al 2014 . neddylation", "2014 . neddylation of the", ". neddylation of the cullin", "neddylation of the cullin subunit", "of the cullin subunit increases", "the cullin subunit increases the", "cullin subunit increases the ubiquitination", "subunit increases the ubiquitination activity", "increases the ubiquitination activity of", "the ubiquitination activity of the", "ubiquitination activity of the crl", "activity of the crl complex", "the crl complex podust", "crl complex podust et", "complex podust et al", "podust et al 2000", "al 2000 read", "2000 read et al", "read et al 2000", "al 2000 wu", "2000 wu et al", "wu et al 2000", "al 2000 kawakami", "2000 kawakami et al", "kawakami et al 2001", "al 2001 ohh", "2001 ohh et al", "ohh et al 2002", "al 2002 yu", "2002 yu et al", "yu et al 2015", "et al 2015 .", "al 2015 . in", "2015 . in addition to", ". in addition to crl", "in addition to crl complexes", "to crl complexes a", "crl complexes a number", "complexes a number of", "a number of other less", "number of other less well", "of other less well characterized", "other less well characterized nedd8", "less well characterized nedd8 targets", "well characterized nedd8 targets have", "characterized nedd8 targets have been", "nedd8 targets have been identified.", "targets have been identified. these", "have been identified. these include", "been identified. these include other", "identified. these include other e3", "these include other e3 ubiquitin", "include other e3 ubiquitin ligases", "other e3 ubiquitin ligases such", "e3 ubiquitin ligases such as", "ubiquitin ligases such as smurf1", "ligases such as smurf1 and", "such as smurf1 and mdm2", "smurf1 and mdm2 receptor", "and mdm2 receptor tyrosine", "mdm2 receptor tyrosine kinases", "receptor tyrosine kinases such as", "tyrosine kinases such as egfr", "kinases such as egfr and", "such as egfr and tgf", "as egfr and tgf beta", "egfr and tgf beta rii", "tgf beta rii and", "beta rii and proteins", "rii and proteins that", "and proteins that contribute to", "proteins that contribute to transcriptional", "that contribute to transcriptional regulation", "to transcriptional regulation among", "transcriptional regulation among others", "among others xie et", "others xie et al", "xie et al 2014", "al 2014 watson", "2014 watson et al", "watson et al 2010", "al 2010 oved", "2010 oved et al", "oved et al 2006", "al 2006 zuo", "2006 zuo et al", "zuo et al 2013", "al 2013 xirodimas", "2013 xirodimas et al", "xirodimas et al 2004", "al 2004 singh", "2004 singh et al", "singh et al 2007", "al 2007 abida", "2007 abida et al", "abida et al 2007", "al 2007 liu", "2007 liu et al", "et al 2010 watson", "al 2010 watson et", "2010 watson et al", "watson et al 2006", "al 2006 loftus", "2006 loftus et al", "loftus et al 2012", "al 2012 aoki", "2012 aoki et al", "aoki et al 2013", "al 2013 reviewed", "2013 reviewed in enchev", "reviewed in enchev et al", "enchev et al 2015", "al 2015 .
like", ".
like ubiquitin nedd8", "
like ubiquitin nedd8 undergoes", "ubiquitin nedd8 undergoes post", "nedd8 undergoes post translational processing", "undergoes post translational processing to", "post translational processing to generate", "translational processing to generate the", "processing to generate the mature", "to generate the mature form.", "generate the mature form. uchl3", "mature form. uchl3 or", "form. uchl3 or senp8", "uchl3 or senp8 mediated", "or senp8 mediated proteolysis removes", "senp8 mediated proteolysis removes the", "mediated proteolysis removes the c", "proteolysis removes the c terminal", "removes the c terminal 5", "the c terminal 5 amino", "c terminal 5 amino acids", "terminal 5 amino acids of", "5 amino acids of nedd8", "acids of nedd8 generating", "of nedd8 generating a", "nedd8 generating a novel", "generating a novel c terminal", "a novel c terminal glycine", "novel c terminal glycine residue", "c terminal glycine residue for", "terminal glycine residue for conjugation", "glycine residue for conjugation to", "residue for conjugation to the", "for conjugation to the cysteine", "conjugation to the cysteine residues", "to the cysteine residues in", "the cysteine residues in the", "cysteine residues in the e1", "in the e1 e2", "the e1 e2 enzymes", "e1 e2 enzymes or", "e2 enzymes or lysine residues", "enzymes or lysine residues in", "or lysine residues in the", "lysine residues in the substrate", "residues in the substrate protein", "the substrate protein usually", "substrate protein usually the", "protein usually the e3", "usually the e3 nedd8 ligase", "the e3 nedd8 ligase itself", "nedd8 ligase itself wada", "ligase itself wada et", "itself wada et al", "wada et al 1998", "al 1998 reviewed", "1998 reviewed in enchev", "al 2015 . most", "2015 . most substrates in", ". most substrates in vivo", "most substrates in vivo appear", "substrates in vivo appear to", "in vivo appear to be", "vivo appear to be singly", "appear to be singly neddylated", "to be singly neddylated on", "be singly neddylated on one", "singly neddylated on one or", "neddylated on one or more", "on one or more lysine", "one or more lysine residues", "more lysine residues but", "lysine residues but nedd8", "residues but nedd8 chains", "but nedd8 chains have been", "nedd8 chains have been formed", "chains have been formed on", "have been formed on cullin", "been formed on cullin substrates", "formed on cullin substrates in", "on cullin substrates in vitro", "cullin substrates in vitro and", "substrates in vitro and on", "in vitro and on histone", "vitro and on histone h4", "and on histone h4 in", "on histone h4 in cultured", "histone h4 in cultured human", "h4 in cultured human cells", "in cultured human cells after", "cultured human cells after dna", "human cells after dna damage", "after dna damage jones", "dna damage jones et", "damage jones et al", "jones et al 2008", "al 2008 ohki", "2008 ohki et al", "ohki et al 2009", "al 2009 xirodimas", "2009 xirodimas et al", "xirodimas et al 2008", "al 2008 jeram", "2008 jeram et al", "jeram et al 2010", "al 2010 ma", "2010 ma et al", "ma et al 2013", "al 2015 . the", "2015 . the significance of", ". the significance of nedd8", "the significance of nedd8 chains", "significance of nedd8 chains is", "of nedd8 chains is still", "nedd8 chains is still not", "chains is still not clear.", "is still not clear.
nedd8", "still not clear.
nedd8 has", "not clear.
nedd8 has a", "clear.
nedd8 has a single", "
nedd8 has a single heterodimeric", "has a single heterodimeric e1", "a single heterodimeric e1 enzyme", "heterodimeric e1 enzyme consisting", "e1 enzyme consisting of", "enzyme consisting of nae1", "consisting of nae1 also", "of nae1 also known", "nae1 also known as", "known as appbp1 and", "as appbp1 and uba3", "and uba3 and two", "uba3 and two e2", "two e2 enzymes ube2m", "e2 enzymes ube2m and", "enzymes ube2m and ube2f", "ube2m and ube2f which", "and ube2f which are", "ube2f which are n", "which are n terminally acetylated", "n terminally acetylated walden", "terminally acetylated walden et", "acetylated walden et al", "walden et al 2003", "al 2003 bohnsack", "2003 bohnsack et al", "bohnsack et al 2003", "al 2003 huang", "2003 huang et al", "huang et al 2004", "al 2004 huang", "2004 huang et al", "huang et al 2005", "al 2005 huang", "2005 huang et al", "huang et al 2009", "al 2009 scott", "2009 scott et al", "scott et al 2011a", "al 2011a monda", "2011a monda et al", "monda et al 2013", "al 2015 . all", "2015 . all nedd8 e3", ". all nedd8 e3 enzymes", "all nedd8 e3 enzymes reported", "nedd8 e3 enzymes reported to", "e3 enzymes reported to date", "enzymes reported to date also", "reported to date also function", "to date also function as", "date also function as e3", "also function as e3 ubiquitin", "function as e3 ubiquitin ligases", "e3 ubiquitin ligases and", "ubiquitin ligases and most", "ligases and most belong", "and most belong to the", "most belong to the ring", "belong to the ring domain", "to the ring domain class.", "the ring domain class. the", "ring domain class. the best", "domain class. the best characterized", "class. the best characterized nedd8", "the best characterized nedd8 e3", "best characterized nedd8 e3 enzymes", "characterized nedd8 e3 enzymes are", "nedd8 e3 enzymes are the", "e3 enzymes are the crl", "enzymes are the crl complexes", "are the crl complexes described", "the crl complexes described above.", "crl complexes described above. rbx1", "complexes described above. rbx1 containing", "described above. rbx1 containing complexes", "above. rbx1 containing complexes interact", "rbx1 containing complexes interact preferentially", "containing complexes interact preferentially with", "complexes interact preferentially with ube2m", "preferentially with ube2m while", "with ube2m while ube2f", "ube2m while ube2f is", "while ube2f is the e2", "ube2f is the e2 for", "is the e2 for rbx2", "the e2 for rbx2 containing", "e2 for rbx2 containing complexes", "rbx2 containing complexes huang", "containing complexes huang et", "complexes huang et al", "al 2009 monda", "2009 monda et al", "al 2013 .
neddylation", "2013 .
neddylation is regulated", ".
neddylation is regulated in", "
neddylation is regulated in vivo", "is regulated in vivo by", "regulated in vivo by interaction", "in vivo by interaction with", "vivo by interaction with dcun1d", "by interaction with dcun1d proteins", "with dcun1d proteins also", "dcun1d proteins also called", "proteins also called dcnls", "also called dcnls . the", "called dcnls . the 5", "dcnls . the 5 human", ". the 5 human dcun1d", "the 5 human dcun1d proteins", "5 human dcun1d proteins interact", "human dcun1d proteins interact both", "dcun1d proteins interact both with", "proteins interact both with cullins", "interact both with cullins and", "both with cullins and with", "with cullins and with the", "cullins and with the nedd8", "and with the nedd8 e2", "with the nedd8 e2 proteins", "the nedd8 e2 proteins and", "nedd8 e2 proteins and thereby", "e2 proteins and thereby increase", "proteins and thereby increase the", "and thereby increase the kinetic", "thereby increase the kinetic efficiency", "increase the kinetic efficiency of", "the kinetic efficiency of neddylation", "efficiency of neddylation kurz", "of neddylation kurz et", "neddylation kurz et al", "kurz et al 2005", "al 2005 kurz", "2005 kurz et al", "kurz et al 2008", "al 2008 scott", "2008 scott et al", "scott et al 2010", "al 2010 scott", "2010 scott et al", "al 2011a scott", "2011a scott et al", "scott et al 2014", "al 2014 monda", "2014 monda et al", "al 2013 . glomulin", "2013 . glomulin glmn", "glomulin glmn is", "glmn is another regulator", "is another regulator of crl", "another regulator of crl function", "regulator of crl function that", "of crl function that binds", "crl function that binds to", "function that binds to the", "that binds to the neddylated", "binds to the neddylated cullin", "to the neddylated cullin and", "the neddylated cullin and competitively", "neddylated cullin and competitively inhibits", "cullin and competitively inhibits interaction", "and competitively inhibits interaction with", "competitively inhibits interaction with the", "inhibits interaction with the ubiquitin", "interaction with the ubiquitin e2", "with the ubiquitin e2 enzyme", "ubiquitin e2 enzyme arai", "e2 enzyme arai et", "enzyme arai et al", "arai et al 2003", "al 2003 tron", "2003 tron et al", "tron et al 2012", "al 2012 duda", "2012 duda et al", "duda et al 2012", "al 2012 reviewed", "2012 reviewed in mahon", "et al 2014 .
the", "al 2014 .
the multisubunit", "2014 .
the multisubunit cop9 signalosome", ".
the multisubunit cop9 signalosome is", "multisubunit cop9 signalosome is the", "cop9 signalosome is the only", "signalosome is the only cullin", "is the only cullin deneddylase", "only cullin deneddylase while", "cullin deneddylase while senp8", "while senp8 also known", "senp8 also known as", "known as den1 contributes", "as den1 contributes to", "den1 contributes to deneddylation", "contributes to deneddylation of other", "to deneddylation of other non", "deneddylation of other non cullin", "of other non cullin nedd8", "other non cullin nedd8 targets", "cullin nedd8 targets cope", "nedd8 targets cope et", "targets cope et al", "cope et al 2002", "al 2002 emberley", "2002 emberley et al", "emberley et al 2012", "al 2012 chan", "2012 chan et al", "chan et al 2008", "al 2008 wu", "2008 wu et al", "wu et al 2003", "al 2003 reviewed", "2003 reviewed in wei", "reviewed in wei et al", "wei et al 2008", "al 2008 enchev", "2008 enchev et al", "2015 . in the deneddylated", ". in the deneddylated state", "the deneddylated state cullins", "deneddylated state cullins bind", "state cullins bind to", "bind to cand1 cullin", "to cand1 cullin associated", "cand1 cullin associated nedd8", "cullin associated nedd8 dissociated protein1", "dissociated protein1 which", "protein1 which displaces", "which displaces the cop9 signalosome", "displaces the cop9 signalosome and", "the cop9 signalosome and promotes", "cop9 signalosome and promotes the", "signalosome and promotes the exchange", "and promotes the exchange of", "promotes the exchange of the", "the exchange of the ubiquitin", "exchange of the ubiquitin substrate", "of the ubiquitin substrate specific", "the ubiquitin substrate specific adaptor.", "ubiquitin substrate specific adaptor. this", "substrate specific adaptor. this allows", "specific adaptor. this allows crl", "adaptor. this allows crl complexes", "this allows crl complexes to", "allows crl complexes to be", "crl complexes to be reconfigured", "complexes to be reconfigured to", "to be reconfigured to target", "be reconfigured to target other", "reconfigured to target other subtrates", "to target other subtrates for", "target other subtrates for ubiquitination", "subtrates for ubiquitination liu", "for ubiquitination liu et", "ubiquitination liu et al", "liu et al 2002", "al 2002 schmidt", "2002 schmidt et al", "schmidt et al 2009", "al 2009 pierce", "2009 pierce et al", "pierce et al 2013", "2013 reviewed in mahon", "et al 2014 .

" ] }, { "record_id": "GLY_000594_1_646", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8953750", "r hsa", "hsa 8953750", "r hsa 8953750" ] }, { "record_id": "GLY_000594_1_646", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation by", "by e2f6", "transcriptional regulation by", "regulation by e2f6", "transcriptional regulation by e2f6", "similar to", "to other", "other e2f", "e2f proteins", "possesses the", "the dna", "dna binding", "binding domain", "the dimerization", "dimerization domain", "domain and", "and the", "the marked", "marked box.", "box. e2f6", "does not", "not have", "have a", "a pocket", "pocket protein", "protein binding", "and thus", "thus does", "not interact", "interact with", "with the", "the retinoblastoma", "retinoblastoma family", "family members", "members rb1", "and rbl2", "gaubatz et", "et al.", "al. 1998", "trimarchi et", "cartwright et", "1998 .", ". e2f6", "e2f6 lacks", "lacks the", "the transactivation", "transactivation domain", "and acts", "acts as", "as a", "a transcriptional", "transcriptional repressor", "e2f6 forms", "forms a", "a heterodimer", "heterodimer with", "with tfdp1", "dp 1", "ogawa et", "al. 2002", "or tfdp2", "dp 2", "1998 .

e2f6", ".

e2f6 knockout", "knockout mice", "mice are", "are viable", "viable and", "and embryonic", "embryonic fibroblasts", "fibroblasts derived", "derived from", "from these", "these mice", "mice proliferate", "proliferate normally.", "normally. although", "although e2f6", "e2f6 knockout", "mice appear", "appear healthy", "they are", "are affected", "affected by", "by homeotic", "homeotic transformations", "transformations of", "of the", "the axial", "axial skeleton", "involving vertebrae", "vertebrae and", "and ribs.", "ribs. similar", "similar skeletal", "skeletal defects", "defects have", "have been", "been reported", "reported in", "in mice", "mice harboring", "harboring mutations", "mutations in", "in polycomb", "polycomb genes", "suggesting that", "that e2f6", "e2f6 may", "may function", "function in", "in recruitment", "recruitment of", "of polycomb", "polycomb repressor", "repressor complex", "complex es", "to target", "target promoters", "storre et", "2002 .

e2f6", ".

e2f6 mediates", "mediates repression", "repression of", "of e2f", "e2f responsive", "responsive genes.", "genes. while", "while e2f6", "e2f6 was", "was suggested", "suggested to", "to maintain", "maintain g0", "g0 state", "state in", "in quiescent", "quiescent cells", "this finding", "finding has", "has been", "been challenged", "giangrande et", "al. 2004", "bertoli et", "al. 2013", "al. 2016", "2016 .", ". instead", "e2f6 mediated", "mediated gene", "gene repression", "repression in", "in proliferating", "non quiescent", "cells is", "is thought", "thought to", "to repress", "repress e2f", "e2f targets", "targets involved", "involved in", "in g1/s", "g1/s transition", "transition during", "during s", "s phase", "phase of", "the cell", "cell cycle.", "cycle. e2f6", "e2f6 does", "not affect", "affect e2f", "in g2/m", "g2/m transition", "oberley et", "al. 2003", "attwooll et", "al. 2005", "trojer et", "al. 2011", "2013 .", ". in", "in the", "the context", "context of", "the e2f6.com", "e2f6.com 1", "1 complex", "was shown", "shown to", "to bind", "bind to", "to promoters", "promoters of", "of e2f1", "cdc25a and", "and tk1", "tk1 genes", "2002 .", "e2f6 also", "also binds", "binds the", "the promoters", "of cdc6", "pcna and", "and tyms", "as well", "well as", "as the", "the promoter", "promoter of", "the dhfr", "dhfr gene", ". while", "while transcriptional", "transcriptional repression", "repression by", "by the", "complex may", "may be", "be associated", "associated with", "with histone", "histone methyltransferase", "methyltransferase activity", "e2f6 can", "can also", "also repress", "repress transcription", "transcription independently", "independently of", "of h3k9", "h3k9 methylation", "2003 .

during", ".

during s", "e2f6 is", "is involved", "dna replication", "replication stress", "stress checkpoint", ". under", "under replication", "chek1 mediated", "mediated phosphorylation", "phosphorylation prevents", "prevents association", "association of", "of e2f6", "e2f6 with", "with its", "its target", "allowing transcription", "transcription of", "e2f target", "target genes", "genes whose", "whose expression", "expression is", "is needed", "needed for", "for resolution", "resolution of", "of stalled", "stalled replication", "replication forks", "forks and", "and restart", "restart of", "of dna", "dna synthesis.", "synthesis. inability", "inability to", "to induce", "induce transcription", "due to", "to chek1", "chek1 inhibition", "inhibition or", "or e2f6", "e2f6 overexpression", "leads to", "to replication", "stress induced", "induced dna", "dna damage", "e2f6 represses", "represses transcription", "of a", "a number", "number of", "in dna", "dna synthesis", "synthesis and", "and repair", "such as", "as rrm2", "and rbbp8", "e2f6 similar", "similar to other", "to other e2f", "other e2f proteins", "proteins possesses", "possesses the dna", "the dna binding", "dna binding domain", "domain the", "the dimerization domain", "dimerization domain and", "domain and the", "and the marked", "the marked box.", "marked box. e2f6", "e2f6 however", "however does", "does not have", "not have a", "have a pocket", "a pocket protein", "pocket protein binding", "protein binding domain", "binding domain and", "domain and thus", "and thus does", "thus does not", "does not interact", "not interact with", "interact with the", "with the retinoblastoma", "the retinoblastoma family", "retinoblastoma family members", "family members rb1", "rb1 rbl1", "rbl1 p107", "p107 and", "rbl2 p130", "gaubatz et al.", "et al. 1998", "1998 trimarchi", "trimarchi et al.", "1998 cartwright", "cartwright et al.", "al. 1998 .", "1998 . e2f6", ". e2f6 lacks", "e2f6 lacks the", "lacks the transactivation", "the transactivation domain", "transactivation domain and", "domain and acts", "and acts as", "acts as a", "as a transcriptional", "a transcriptional repressor", "repressor gaubatz", ". e2f6 forms", "e2f6 forms a", "forms a heterodimer", "a heterodimer with", "heterodimer with tfdp1", "tfdp1 dp", "1998 ogawa", "ogawa et al.", "et al. 2002", "2002 cartwright", "1998 or", "tfdp2 dp", "al. 1998 .

e2f6", "1998 .

e2f6 knockout", ".

e2f6 knockout mice", "knockout mice are", "mice are viable", "are viable and", "viable and embryonic", "and embryonic fibroblasts", "embryonic fibroblasts derived", "fibroblasts derived from", "derived from these", "from these mice", "these mice proliferate", "mice proliferate normally.", "proliferate normally. although", "normally. although e2f6", "although e2f6 knockout", "e2f6 knockout mice", "knockout mice appear", "mice appear healthy", "healthy they", "they are affected", "are affected by", "affected by homeotic", "by homeotic transformations", "homeotic transformations of", "transformations of the", "of the axial", "the axial skeleton", "skeleton involving", "involving vertebrae and", "vertebrae and ribs.", "and ribs. similar", "ribs. similar skeletal", "similar skeletal defects", "skeletal defects have", "defects have been", "have been reported", "been reported in", "reported in mice", "in mice harboring", "mice harboring mutations", "harboring mutations in", "mutations in polycomb", "in polycomb genes", "genes suggesting", "suggesting that e2f6", "that e2f6 may", "e2f6 may function", "may function in", "function in recruitment", "in recruitment of", "recruitment of polycomb", "of polycomb repressor", "polycomb repressor complex", "repressor complex es", "es to", "to target promoters", "promoters storre", "storre et al.", "al. 2002 .

e2f6", "2002 .

e2f6 mediates", ".

e2f6 mediates repression", "mediates repression of", "repression of e2f", "of e2f responsive", "e2f responsive genes.", "responsive genes. while", "genes. while e2f6", "while e2f6 was", "e2f6 was suggested", "was suggested to", "suggested to maintain", "to maintain g0", "maintain g0 state", "g0 state in", "state in quiescent", "in quiescent cells", "cells gaubatz", "this finding has", "finding has been", "has been challenged", "challenged giangrande", "giangrande et al.", "et al. 2004", "2004 bertoli", "bertoli et al.", "et al. 2013", "2013 bertoli", "et al. 2016", "al. 2016 .", "2016 . instead", "instead e2f6", "e2f6 mediated gene", "mediated gene repression", "gene repression in", "repression in proliferating", "proliferating non", "cells is thought", "is thought to", "thought to repress", "to repress e2f", "repress e2f targets", "e2f targets involved", "targets involved in", "involved in g1/s", "in g1/s transition", "g1/s transition during", "transition during s", "during s phase", "s phase of", "phase of the", "of the cell", "the cell cycle.", "cell cycle. e2f6", "cycle. e2f6 does", "e2f6 does not", "does not affect", "not affect e2f", "affect e2f targets", "involved in g2/m", "in g2/m transition", "transition oberley", "oberley et al.", "et al. 2003", "2003 giangrande", "2004 attwooll", "attwooll et al.", "et al. 2005", "2005 trojer", "trojer et al.", "et al. 2011", "2011 bertoli", "al. 2013 .", "2013 . in", ". in the", "in the context", "the context of", "context of the", "of the e2f6.com", "the e2f6.com 1", "e2f6.com 1 complex", "complex e2f6", "e2f6 was shown", "was shown to", "shown to bind", "to bind to", "bind to promoters", "to promoters of", "promoters of e2f1", "e2f1 myc", "myc cdc25a", "cdc25a and tk1", "and tk1 genes", "genes ogawa", "al. 2002 .", "2002 . e2f6", ". e2f6 also", "e2f6 also binds", "also binds the", "binds the promoters", "the promoters of", "promoters of cdc6", "cdc6 rrm1", "rrm1 rr1", "pcna and tyms", "tyms ts", "ts genes", "genes giangrande", "as well as", "well as the", "as the promoter", "the promoter of", "promoter of the", "of the dhfr", "the dhfr gene", "gene gaubatz", "1998 . while", ". while transcriptional", "while transcriptional repression", "transcriptional repression by", "repression by the", "by the e2f6.com", "1 complex may", "complex may be", "may be associated", "be associated with", "associated with histone", "with histone methyltransferase", "histone methyltransferase activity", "activity ogawa", "e2f6 can also", "can also repress", "also repress transcription", "repress transcription independently", "transcription independently of", "independently of h3k9", "of h3k9 methylation", "methylation oberley", "al. 2003 .

during", "2003 .

during s", ".

during s phase", "phase e2f6", "e2f6 is involved", "is involved in", "involved in the", "in the dna", "the dna replication", "dna replication stress", "replication stress checkpoint", "checkpoint bertoli", "2016 . under", ". under replication", "under replication stress", "stress chek1", "chek1 mediated phosphorylation", "mediated phosphorylation prevents", "phosphorylation prevents association", "prevents association of", "association of e2f6", "of e2f6 with", "e2f6 with its", "with its target", "its target promoters", "promoters allowing", "allowing transcription of", "transcription of e2f", "of e2f target", "e2f target genes", "target genes whose", "genes whose expression", "whose expression is", "expression is needed", "is needed for", "needed for resolution", "for resolution of", "resolution of stalled", "of stalled replication", "stalled replication forks", "replication forks and", "forks and restart", "and restart of", "restart of dna", "of dna synthesis.", "dna synthesis. inability", "synthesis. inability to", "inability to induce", "to induce transcription", "induce transcription of", "genes due", "due to chek1", "to chek1 inhibition", "chek1 inhibition or", "inhibition or e2f6", "or e2f6 overexpression", "overexpression leads", "leads to replication", "to replication stress", "replication stress induced", "stress induced dna", "induced dna damage", "damage bertoli", "2016 . e2f6", ". e2f6 represses", "e2f6 represses transcription", "represses transcription of", "transcription of a", "of a number", "a number of", "number of e2f", "of e2f targets", "involved in dna", "in dna synthesis", "dna synthesis and", "synthesis and repair", "repair such", "such as rrm2", "rrm2 rad51", "rad51 brca1", "brca1 and", "rbbp8 oberley", "2003 bertoli", "e2f6 similar to", "similar to other e2f", "to other e2f proteins", "e2f proteins possesses", "proteins possesses the", "possesses the dna binding", "the dna binding domain", "binding domain the", "domain the dimerization", "the dimerization domain and", "dimerization domain and the", "domain and the marked", "and the marked box.", "the marked box. e2f6", "box. e2f6 however", "however does not", "does not have a", "not have a pocket", "have a pocket protein", "a pocket protein binding", "pocket protein binding domain", "protein binding domain and", "binding domain and thus", "domain and thus does", "and thus does not", "thus does not interact", "does not interact with", "not interact with the", "interact with the retinoblastoma", "with the retinoblastoma family", "the retinoblastoma family members", "retinoblastoma family members rb1", "members rb1 rbl1", "p107 and rbl2", "and rbl2 p130", "p130 gaubatz", "gaubatz et al. 1998", "al. 1998 trimarchi", "1998 trimarchi et", "trimarchi et al. 1998", "al. 1998 cartwright", "1998 cartwright et", "cartwright et al. 1998", "et al. 1998 .", "al. 1998 . e2f6", "1998 . e2f6 lacks", ". e2f6 lacks the", "e2f6 lacks the transactivation", "lacks the transactivation domain", "the transactivation domain and", "transactivation domain and acts", "domain and acts as", "and acts as a", "acts as a transcriptional", "as a transcriptional repressor", "transcriptional repressor gaubatz", "repressor gaubatz et", "1998 . e2f6 forms", ". e2f6 forms a", "e2f6 forms a heterodimer", "forms a heterodimer with", "a heterodimer with tfdp1", "with tfdp1 dp", "tfdp1 dp 1", "1 trimarchi", "al. 1998 ogawa", "1998 ogawa et", "ogawa et al. 2002", "al. 2002 cartwright", "2002 cartwright et", "al. 1998 or", "1998 or tfdp2", "or tfdp2 dp", "tfdp2 dp 2", "2 gaubatz", "et al. 1998 .

e2f6", "al. 1998 .

e2f6 knockout", "1998 .

e2f6 knockout mice", ".

e2f6 knockout mice are", "knockout mice are viable", "mice are viable and", "are viable and embryonic", "viable and embryonic fibroblasts", "and embryonic fibroblasts derived", "embryonic fibroblasts derived from", "fibroblasts derived from these", "derived from these mice", "from these mice proliferate", "these mice proliferate normally.", "mice proliferate normally. although", "proliferate normally. although e2f6", "normally. although e2f6 knockout", "although e2f6 knockout mice", "e2f6 knockout mice appear", "knockout mice appear healthy", "appear healthy they", "healthy they are", "they are affected by", "are affected by homeotic", "affected by homeotic transformations", "by homeotic transformations of", "homeotic transformations of the", "transformations of the axial", "of the axial skeleton", "axial skeleton involving", "skeleton involving vertebrae", "involving vertebrae and ribs.", "vertebrae and ribs. similar", "and ribs. similar skeletal", "ribs. similar skeletal defects", "similar skeletal defects have", "skeletal defects have been", "defects have been reported", "have been reported in", "been reported in mice", "reported in mice harboring", "in mice harboring mutations", "mice harboring mutations in", "harboring mutations in polycomb", "mutations in polycomb genes", "polycomb genes suggesting", "genes suggesting that", "suggesting that e2f6 may", "that e2f6 may function", "e2f6 may function in", "may function in recruitment", "function in recruitment of", "in recruitment of polycomb", "recruitment of polycomb repressor", "of polycomb repressor complex", "polycomb repressor complex es", "complex es to", "es to target", "target promoters storre", "promoters storre et", "storre et al. 2002", "et al. 2002 .

e2f6", "al. 2002 .

e2f6 mediates", "2002 .

e2f6 mediates repression", ".

e2f6 mediates repression of", "mediates repression of e2f", "repression of e2f responsive", "of e2f responsive genes.", "e2f responsive genes. while", "responsive genes. while e2f6", "genes. while e2f6 was", "while e2f6 was suggested", "e2f6 was suggested to", "was suggested to maintain", "suggested to maintain g0", "to maintain g0 state", "maintain g0 state in", "g0 state in quiescent", "state in quiescent cells", "quiescent cells gaubatz", "cells gaubatz et", "2002 this", "this finding has been", "finding has been challenged", "been challenged giangrande", "challenged giangrande et", "giangrande et al. 2004", "al. 2004 bertoli", "2004 bertoli et", "bertoli et al. 2013", "al. 2013 bertoli", "2013 bertoli et", "bertoli et al. 2016", "et al. 2016 .", "al. 2016 . instead", ". instead e2f6", "instead e2f6 mediated", "e2f6 mediated gene repression", "mediated gene repression in", "gene repression in proliferating", "in proliferating non", "proliferating non quiescent", "non quiescent cells", "quiescent cells is", "cells is thought to", "is thought to repress", "thought to repress e2f", "to repress e2f targets", "repress e2f targets involved", "e2f targets involved in", "targets involved in g1/s", "involved in g1/s transition", "in g1/s transition during", "g1/s transition during s", "transition during s phase", "during s phase of", "s phase of the", "phase of the cell", "of the cell cycle.", "the cell cycle. e2f6", "cell cycle. e2f6 does", "cycle. e2f6 does not", "e2f6 does not affect", "does not affect e2f", "not affect e2f targets", "affect e2f targets involved", "targets involved in g2/m", "involved in g2/m transition", "g2/m transition oberley", "transition oberley et", "oberley et al. 2003", "al. 2003 giangrande", "2003 giangrande et", "al. 2004 attwooll", "2004 attwooll et", "attwooll et al. 2005", "al. 2005 trojer", "2005 trojer et", "trojer et al. 2011", "al. 2011 bertoli", "2011 bertoli et", "et al. 2013 .", "al. 2013 . in", "2013 . in the", ". in the context", "in the context of", "the context of the", "context of the e2f6.com", "of the e2f6.com 1", "the e2f6.com 1 complex", "1 complex e2f6", "complex e2f6 was", "e2f6 was shown to", "was shown to bind", "shown to bind to", "to bind to promoters", "bind to promoters of", "to promoters of e2f1", "of e2f1 myc", "myc cdc25a and", "cdc25a and tk1 genes", "tk1 genes ogawa", "genes ogawa et", "et al. 2002 .", "al. 2002 . e2f6", "2002 . e2f6 also", ". e2f6 also binds", "e2f6 also binds the", "also binds the promoters", "binds the promoters of", "the promoters of cdc6", "of cdc6 rrm1", "rr1 pcna", "and tyms ts", "genes giangrande et", "2004 as", "as well as the", "well as the promoter", "as the promoter of", "the promoter of the", "promoter of the dhfr", "of the dhfr gene", "dhfr gene gaubatz", "gene gaubatz et", "al. 1998 . while", "1998 . while transcriptional", ". while transcriptional repression", "while transcriptional repression by", "transcriptional repression by the", "repression by the e2f6.com", "by the e2f6.com 1", "e2f6.com 1 complex may", "1 complex may be", "complex may be associated", "may be associated with", "be associated with histone", "associated with histone methyltransferase", "with histone methyltransferase activity", "methyltransferase activity ogawa", "activity ogawa et", "2002 e2f6", "e2f6 can also repress", "can also repress transcription", "also repress transcription independently", "repress transcription independently of", "transcription independently of h3k9", "independently of h3k9 methylation", "h3k9 methylation oberley", "methylation oberley et", "et al. 2003 .

during", "al. 2003 .

during s", "2003 .

during s phase", "s phase e2f6", "phase e2f6 is", "e2f6 is involved in", "is involved in the", "involved in the dna", "in the dna replication", "the dna replication stress", "dna replication stress checkpoint", "stress checkpoint bertoli", "checkpoint bertoli et", "al. 2016 . under", "2016 . under replication", ". under replication stress", "replication stress chek1", "stress chek1 mediated", "chek1 mediated phosphorylation prevents", "mediated phosphorylation prevents association", "phosphorylation prevents association of", "prevents association of e2f6", "association of e2f6 with", "of e2f6 with its", "e2f6 with its target", "with its target promoters", "target promoters allowing", "promoters allowing transcription", "allowing transcription of e2f", "transcription of e2f target", "of e2f target genes", "e2f target genes whose", "target genes whose expression", "genes whose expression is", "whose expression is needed", "expression is needed for", "is needed for resolution", "needed for resolution of", "for resolution of stalled", "resolution of stalled replication", "of stalled replication forks", "stalled replication forks and", "replication forks and restart", "forks and restart of", "and restart of dna", "restart of dna synthesis.", "of dna synthesis. inability", "dna synthesis. inability to", "synthesis. inability to induce", "inability to induce transcription", "to induce transcription of", "induce transcription of e2f", "target genes due", "genes due to", "due to chek1 inhibition", "to chek1 inhibition or", "chek1 inhibition or e2f6", "inhibition or e2f6 overexpression", "e2f6 overexpression leads", "overexpression leads to", "leads to replication stress", "to replication stress induced", "replication stress induced dna", "stress induced dna damage", "dna damage bertoli", "damage bertoli et", "al. 2016 . e2f6", "2016 . e2f6 represses", ". e2f6 represses transcription", "e2f6 represses transcription of", "represses transcription of a", "transcription of a number", "of a number of", "a number of e2f", "number of e2f targets", "of e2f targets involved", "targets involved in dna", "involved in dna synthesis", "in dna synthesis and", "dna synthesis and repair", "and repair such", "repair such as", "as rrm2 rad51", "brca1 and rbbp8", "and rbbp8 oberley", "rbbp8 oberley et", "al. 2003 bertoli", "2003 bertoli et", "e2f6 similar to other", "similar to other e2f proteins", "other e2f proteins possesses", "e2f proteins possesses the", "proteins possesses the dna", "possesses the dna binding domain", "dna binding domain the", "binding domain the dimerization", "domain the dimerization domain", "the dimerization domain and the", "dimerization domain and the marked", "domain and the marked box.", "and the marked box. e2f6", "marked box. e2f6 however", "e2f6 however does", "however does not have", "does not have a pocket", "not have a pocket protein", "have a pocket protein binding", "a pocket protein binding domain", "pocket protein binding domain and", "protein binding domain and thus", "binding domain and thus does", "domain and thus does not", "and thus does not interact", "thus does not interact with", "does not interact with the", "not interact with the retinoblastoma", "interact with the retinoblastoma family", "with the retinoblastoma family members", "the retinoblastoma family members rb1", "family members rb1 rbl1", "rb1 rbl1 p107", "rbl1 p107 and", "p130 gaubatz et", "et al. 1998 trimarchi", "al. 1998 trimarchi et", "1998 trimarchi et al.", "et al. 1998 cartwright", "al. 1998 cartwright et", "1998 cartwright et al.", "cartwright et al. 1998 .", "et al. 1998 . e2f6", "al. 1998 . e2f6 lacks", "1998 . e2f6 lacks the", ". e2f6 lacks the transactivation", "e2f6 lacks the transactivation domain", "lacks the transactivation domain and", "the transactivation domain and acts", "transactivation domain and acts as", "domain and acts as a", "and acts as a transcriptional", "acts as a transcriptional repressor", "a transcriptional repressor gaubatz", "transcriptional repressor gaubatz et", "repressor gaubatz et al.", "al. 1998 . e2f6 forms", "1998 . e2f6 forms a", ". e2f6 forms a heterodimer", "e2f6 forms a heterodimer with", "forms a heterodimer with tfdp1", "heterodimer with tfdp1 dp", "with tfdp1 dp 1", "dp 1 trimarchi", "1 trimarchi et", "et al. 1998 ogawa", "al. 1998 ogawa et", "1998 ogawa et al.", "et al. 2002 cartwright", "al. 2002 cartwright et", "2002 cartwright et al.", "et al. 1998 or", "al. 1998 or tfdp2", "or tfdp2 dp 2", "dp 2 gaubatz", "2 gaubatz et", "cartwright et al. 1998 .

e2f6", "et al. 1998 .

e2f6 knockout", "al. 1998 .

e2f6 knockout mice", "1998 .

e2f6 knockout mice are", ".

e2f6 knockout mice are viable", "knockout mice are viable and", "mice are viable and embryonic", "are viable and embryonic fibroblasts", "viable and embryonic fibroblasts derived", "and embryonic fibroblasts derived from", "embryonic fibroblasts derived from these", "fibroblasts derived from these mice", "derived from these mice proliferate", "from these mice proliferate normally.", "these mice proliferate normally. although", "mice proliferate normally. although e2f6", "proliferate normally. although e2f6 knockout", "normally. although e2f6 knockout mice", "although e2f6 knockout mice appear", "e2f6 knockout mice appear healthy", "mice appear healthy they", "appear healthy they are", "healthy they are affected", "they are affected by homeotic", "are affected by homeotic transformations", "affected by homeotic transformations of", "by homeotic transformations of the", "homeotic transformations of the axial", "transformations of the axial skeleton", "the axial skeleton involving", "axial skeleton involving vertebrae", "skeleton involving vertebrae and", "involving vertebrae and ribs. similar", "vertebrae and ribs. similar skeletal", "and ribs. similar skeletal defects", "ribs. similar skeletal defects have", "similar skeletal defects have been", "skeletal defects have been reported", "defects have been reported in", "have been reported in mice", "been reported in mice harboring", "reported in mice harboring mutations", "in mice harboring mutations in", "mice harboring mutations in polycomb", "harboring mutations in polycomb genes", "in polycomb genes suggesting", "polycomb genes suggesting that", "genes suggesting that e2f6", "suggesting that e2f6 may function", "that e2f6 may function in", "e2f6 may function in recruitment", "may function in recruitment of", "function in recruitment of polycomb", "in recruitment of polycomb repressor", "recruitment of polycomb repressor complex", "of polycomb repressor complex es", "repressor complex es to", "complex es to target", "es to target promoters", "to target promoters storre", "target promoters storre et", "promoters storre et al.", "storre et al. 2002 .

e2f6", "et al. 2002 .

e2f6 mediates", "al. 2002 .

e2f6 mediates repression", "2002 .

e2f6 mediates repression of", ".

e2f6 mediates repression of e2f", "mediates repression of e2f responsive", "repression of e2f responsive genes.", "of e2f responsive genes. while", "e2f responsive genes. while e2f6", "responsive genes. while e2f6 was", "genes. while e2f6 was suggested", "while e2f6 was suggested to", "e2f6 was suggested to maintain", "was suggested to maintain g0", "suggested to maintain g0 state", "to maintain g0 state in", "maintain g0 state in quiescent", "g0 state in quiescent cells", "in quiescent cells gaubatz", "quiescent cells gaubatz et", "cells gaubatz et al.", "al. 2002 this", "2002 this finding", "this finding has been challenged", "has been challenged giangrande", "been challenged giangrande et", "challenged giangrande et al.", "et al. 2004 bertoli", "al. 2004 bertoli et", "2004 bertoli et al.", "et al. 2013 bertoli", "al. 2013 bertoli et", "2013 bertoli et al.", "bertoli et al. 2016 .", "et al. 2016 . instead", "2016 . instead e2f6", ". instead e2f6 mediated", "instead e2f6 mediated gene", "e2f6 mediated gene repression in", "mediated gene repression in proliferating", "repression in proliferating non", "in proliferating non quiescent", "non quiescent cells is", "quiescent cells is thought", "cells is thought to repress", "is thought to repress e2f", "thought to repress e2f targets", "to repress e2f targets involved", "repress e2f targets involved in", "e2f targets involved in g1/s", "targets involved in g1/s transition", "involved in g1/s transition during", "in g1/s transition during s", "g1/s transition during s phase", "transition during s phase of", "during s phase of the", "s phase of the cell", "phase of the cell cycle.", "of the cell cycle. e2f6", "the cell cycle. e2f6 does", "cell cycle. e2f6 does not", "cycle. e2f6 does not affect", "e2f6 does not affect e2f", "does not affect e2f targets", "not affect e2f targets involved", "affect e2f targets involved in", "e2f targets involved in g2/m", "targets involved in g2/m transition", "in g2/m transition oberley", "g2/m transition oberley et", "transition oberley et al.", "et al. 2003 giangrande", "al. 2003 giangrande et", "2003 giangrande et al.", "et al. 2004 attwooll", "al. 2004 attwooll et", "2004 attwooll et al.", "et al. 2005 trojer", "al. 2005 trojer et", "2005 trojer et al.", "et al. 2011 bertoli", "al. 2011 bertoli et", "2011 bertoli et al.", "bertoli et al. 2013 .", "et al. 2013 . in", "al. 2013 . in the", "2013 . in the context", ". in the context of", "in the context of the", "the context of the e2f6.com", "context of the e2f6.com 1", "of the e2f6.com 1 complex", "e2f6.com 1 complex e2f6", "1 complex e2f6 was", "complex e2f6 was shown", "e2f6 was shown to bind", "was shown to bind to", "shown to bind to promoters", "to bind to promoters of", "bind to promoters of e2f1", "promoters of e2f1 myc", "e2f1 myc cdc25a", "myc cdc25a and tk1", "and tk1 genes ogawa", "tk1 genes ogawa et", "genes ogawa et al.", "ogawa et al. 2002 .", "et al. 2002 . e2f6", "al. 2002 . e2f6 also", "2002 . e2f6 also binds", ". e2f6 also binds the", "e2f6 also binds the promoters", "also binds the promoters of", "binds the promoters of cdc6", "promoters of cdc6 rrm1", "cdc6 rrm1 rr1", "rr1 pcna and", "pcna and tyms ts", "tyms ts genes", "ts genes giangrande", "genes giangrande et al.", "al. 2004 as", "2004 as well", "as well as the promoter", "well as the promoter of", "as the promoter of the", "the promoter of the dhfr", "promoter of the dhfr gene", "the dhfr gene gaubatz", "dhfr gene gaubatz et", "gene gaubatz et al.", "gaubatz et al. 1998 .", "et al. 1998 . while", "al. 1998 . while transcriptional", "1998 . while transcriptional repression", ". while transcriptional repression by", "while transcriptional repression by the", "transcriptional repression by the e2f6.com", "repression by the e2f6.com 1", "by the e2f6.com 1 complex", "the e2f6.com 1 complex may", "e2f6.com 1 complex may be", "1 complex may be associated", "complex may be associated with", "may be associated with histone", "be associated with histone methyltransferase", "associated with histone methyltransferase activity", "histone methyltransferase activity ogawa", "methyltransferase activity ogawa et", "activity ogawa et al.", "al. 2002 e2f6", "2002 e2f6 can", "e2f6 can also repress transcription", "can also repress transcription independently", "also repress transcription independently of", "repress transcription independently of h3k9", "transcription independently of h3k9 methylation", "of h3k9 methylation oberley", "h3k9 methylation oberley et", "methylation oberley et al.", "oberley et al. 2003 .

during", "et al. 2003 .

during s", "al. 2003 .

during s phase", ".

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trisphosphate pip3", "pip3 recruits", "recruits the non receptor", "the non receptor tyrosine", "non receptor tyrosine protein", "receptor tyrosine protein kinase", "tyrosine protein kinase btk", "protein kinase btk to", "kinase btk to the", "btk to the cell", "to the cell membrane.", "the cell membrane. here", "membrane. here the", "here the g", "the g protein beta", "beta gamma complex activates", "gamma complex activates btk.", "complex activates btk. subsequently", "btk. subsequently active", "subsequently active btk", "active btk dissociates from", "btk dissociates from the", "dissociates from the complex", "from the complex to", "the complex to phosphorylate", "complex to phosphorylate downstream", "to phosphorylate downstream substrates.", "phosphorylate downstream substrates. physiologically", "substrates. physiologically btk", "physiologically btk plays", "btk plays a key", "plays a key role", "a key role in", "key role in b", "role in b lymphocyte", "in b lymphocyte development", "lymphocyte development differentiation", "development differentiation and", "protein coupled receptors gpcr", "receptors gpcr sense", "gpcr sense extracellular signals", "sense extracellular signals and activate", "extracellular signals and activate different", "signals and activate different guanine", "and activate different guanine nucleotide", "activate different guanine nucleotide binding", "different guanine nucleotide binding proteins", "nucleotide binding proteins g", "binding proteins g proteins", "g proteins that have", "proteins that have alpha", "that have alpha beta", "have alpha beta and", "alpha beta and gamma", "beta and gamma subunits. upon", "and gamma subunits. upon activation", "subunits. upon activation the", "upon activation the alpha", "activation the alpha subunit", "the alpha subunit of g", "alpha subunit of g proteins", "subunit of g proteins dissociates", "of g proteins dissociates from", "g proteins dissociates from beta", "proteins dissociates from beta gamma", "dissociates from beta gamma and", "from beta gamma and the", "beta gamma and the both", "gamma and the both are", "and the both are then", "the both are then free", "both are then free to", "are then free to regulate", "then free to regulate downstream", "free to regulate downstream effectors.", "to regulate downstream effectors. g", "regulate downstream effectors. g protein", "downstream effectors. g protein beta", "effectors. g protein beta gamma", "g protein beta gamma complex", "beta gamma complex along", "gamma complex along with", "complex along with phosphatidylinositol", "along with phosphatidylinositol 3 4", "with phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "4 5 trisphosphate pip3", "pip3 recruits the", "recruits the non receptor tyrosine", "the non receptor tyrosine protein", "non receptor tyrosine protein kinase", "receptor tyrosine protein kinase btk", "tyrosine protein kinase btk to", "protein kinase btk to the", "kinase btk to the cell", "btk to the cell membrane.", "to the cell membrane. here", "cell membrane. here the", "membrane. here the g", "here the g protein", "the g protein beta gamma", "protein beta gamma complex activates", "beta gamma complex activates btk.", "gamma complex activates btk. subsequently", "activates btk. subsequently active", "btk. subsequently active btk", "subsequently active btk dissociates", "active btk dissociates from the", "btk dissociates from the complex", "dissociates from the complex to", "from the complex to phosphorylate", "the complex to phosphorylate downstream", "complex to phosphorylate downstream substrates.", "to phosphorylate downstream substrates. physiologically", "downstream substrates. physiologically btk", "substrates. physiologically btk plays", "physiologically btk plays a", "btk plays a key role", "plays a key role in", "a key role in b", "key role in b lymphocyte", "role in b lymphocyte development", "b lymphocyte development differentiation", "lymphocyte development differentiation and", "development differentiation and signalling." ] }, { "record_id": "GLY_000594_1_651", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8964572", "r hsa", "hsa 8964572", "r hsa 8964572" ] }, { "record_id": "GLY_000594_1_651", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lipid particle", "particle organization", "lipid particle organization", "lipid droplets", "are cytosolic", "cytosolic structures", "structures found", "found in", "in cells", "cells of", "of all", "all eukaryotes", "comprising a", "a monolayer", "monolayer of", "of phospholipids", "phospholipids surrounding", "surrounding a", "a core", "core of", "of uncharged", "uncharged lipids", "lipids such", "such as", "as triglyceride", "and sterol", "sterol esters.", "esters. cidea", "cideb and", "and cidec", "cidec were", "were first", "first studied", "studied for", "for their", "their 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"disease. hypoxia", "hypoxia inducible", "inducible lipid", "lipid droplet", "droplet associated", "associated protein", "a lipid", "droplet protein", "protein and", "and stimulates", "stimulates intracellular", "intracellular lipid", "lipid accumulation.", "droplets lds", "lds are", "are cytosolic structures", "cytosolic structures found", "structures found in", "found in cells", "in cells of", "cells of all", "of all eukaryotes", "eukaryotes comprising", "comprising a monolayer", "a monolayer of", "monolayer of phospholipids", "of phospholipids surrounding", "phospholipids surrounding a", "surrounding a core", "a core of", "core of uncharged", "of uncharged lipids", "uncharged lipids such", "lipids such as", "such as triglyceride", "triglyceride tag", "tag and", "and sterol esters.", "sterol esters. cidea", "cidea cideb", "cideb and cidec", "and cidec were", "cidec were first", "were first studied", "first studied for", "studied for their", "for their roles", "their roles in", "roles 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associated", "droplet associated protein", "protein hilpda", "hilpda is", "is a lipid", "a lipid droplet", "lipid droplet protein", "droplet protein and", "protein and stimulates", "and stimulates intracellular", "stimulates intracellular lipid", "intracellular lipid accumulation.", "lipid droplets lds", "lds are cytosolic", "are cytosolic structures found", "cytosolic structures found in", "structures found in cells", "found in cells of", "in cells of all", "cells of all eukaryotes", "all eukaryotes comprising", "eukaryotes comprising a", "comprising a monolayer of", "a monolayer of phospholipids", "monolayer of phospholipids surrounding", "of phospholipids surrounding a", "phospholipids surrounding a core", "surrounding a core of", "a core of uncharged", "core of uncharged lipids", "of uncharged lipids such", "uncharged lipids such as", "lipids such as triglyceride", "as triglyceride tag", "tag and sterol", "and sterol esters. cidea", "esters. cidea cideb", "cidea cideb and", "cideb 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triglyceride tag", "triglyceride tag and", "tag and sterol esters.", "sterol esters. cidea cideb", "esters. cidea cideb and", "cidea cideb and cidec", "cideb and cidec were first", "and cidec were first studied", "cidec were first studied for", "were first studied for their", "first studied for their roles", "studied for their roles in", "for their roles in promotion", "their roles in promotion of", "roles in promotion of apoptosis", "in promotion of apoptosis but", "promotion of apoptosis but they", "of apoptosis but they are", "apoptosis but they are also", "but they are also known", "they are also known to", "are also known to play", "also known to play a", "known to play a role", "to play a role in", "play a role in energy", "a role in energy metabolism.", "role in energy metabolism. cidea", "in energy metabolism. cidea and", "energy metabolism. cidea and c", "metabolism. cidea and c bind", "cidea and c bind to", "and c bind to lipid", "c bind to lipid droplets", "bind to lipid droplets and", "to lipid droplets and regulate", "lipid droplets and regulate their", "droplets and regulate their enlargement", "regulate their enlargement thereby", "their enlargement thereby restricting", "enlargement thereby restricting lipolysis", "thereby restricting lipolysis and favouring", "restricting lipolysis and favouring storage", "and favouring storage by", "favouring storage by promoting", "storage by promoting net", "by promoting net neutral lipid", "promoting net neutral lipid transfer", "net neutral lipid transfer from", "neutral lipid transfer from smaller", "lipid transfer from smaller to", "transfer from smaller to larger", "from smaller to larger lipid", "smaller to larger lipid droplets", "lipid droplets gao", "droplets gao &", "gao & goodman 2015 .", "& goodman 2015 . ld", "goodman 2015 . ld formation", "2015 . ld formation involves", ". ld formation involves the", "ld formation involves the partitioning", "formation involves the partitioning of", "involves the partitioning of neutral", "the partitioning of neutral lipids", "partitioning of neutral lipids from", "of neutral lipids from their", "neutral lipids from their site", "lipids from their site of", "from their site of synthesis", "their site of synthesis at", "site of synthesis at the", "of synthesis at the endoplasmic", "synthesis at the endoplasmic reticulum", "the endoplasmic reticulum er", "reticulum er to", "er to the cytosol.", "to the cytosol. the fat", "the cytosol. the fat storage", "cytosol. the fat storage inducing", "the fat storage inducing transmembrane", "fat storage inducing transmembrane proteins", "storage inducing transmembrane proteins 1", "inducing transmembrane proteins 1 and", "transmembrane proteins 1 and 2", "1 and 2 fitm1", "and 2 fitm1 and", "2 fitm1 and fitm2", "and fitm2 associated", "fitm2 associated with", "associated with the er membrane", "the er membrane mediate", "er membrane mediate binding", "membrane mediate binding and", "mediate binding and partitioning of", "binding and partitioning of tags", "and partitioning of tags into", "partitioning of tags into lds.", "of tags into lds. the", "tags into lds. the short", "into lds. the short chain", "lds. the short chain dehydrogenases/reductases", "short chain dehydrogenases/reductases sdr", "dehydrogenases/reductases sdr family", "sdr family is a", "family is a large family", "is a large family of", "a large family of nad", "family of nad or", "of nad or nadp", "nad or nadp dependent", "or nadp dependent oxidoreductase enzymes.", "nadp dependent oxidoreductase enzymes. 17", "dependent oxidoreductase enzymes. 17 beta", "oxidoreductase enzymes. 17 beta hydroxysteroid", "enzymes. 17 beta hydroxysteroid dehydrogenase", "17 beta hydroxysteroid dehydrogenase 13", "hydroxysteroid dehydrogenase 13 hsd17b13", "13 hsd17b13 is", "hsd17b13 is a recently", "is a recently discovered enzyme", "a recently discovered enzyme of", "recently discovered enzyme of unknown", "discovered enzyme of 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"droplet associated protein hilpda", "protein hilpda is", "hilpda is a lipid", "is a lipid droplet protein", "a lipid droplet protein and", "lipid droplet protein and stimulates", "droplet protein and stimulates intracellular", "protein and stimulates intracellular lipid", "and stimulates intracellular lipid accumulation." ] }, { "record_id": "GLY_000594_1_652", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8964616", "r hsa", "hsa 8964616", "r hsa 8964616" ] }, { "record_id": "GLY_000594_1_652", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "g beta:gamma", "beta:gamma signalling", "signalling through", "through cdc42", "g beta:gamma signalling", "beta:gamma signalling through", "signalling through cdc42", "g beta:gamma signalling through", "beta:gamma signalling through cdc42", "g beta:gamma signalling through cdc42", "g protein", "protein coupled", "coupled receptors", "sense 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division control", "activates cell division control protein", "cell division control protein 42", "division control protein 42 homolog", "protein 42 homolog cdc42", "homolog cdc42 by", "cdc42 by acting as", "by acting as a gef.", "acting as a gef. once", "as a gef. once active", "gef. once active cdc42", "once active cdc42 can", "active cdc42 can facilitate", "cdc42 can facilitate the activation", "can facilitate the activation of", "facilitate the activation of pak1.", "the activation of pak1. cdc42", "activation of pak1. cdc42 is", "of pak1. cdc42 is known", "pak1. cdc42 is known to", "cdc42 is known to be", "is known to be involved", "known to be involved in", "to be involved in epithelial", "be involved in epithelial cell", "involved in epithelial cell polarization", "in epithelial cell polarization processes." ] }, { "record_id": "GLY_000594_1_653", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8983711", "r hsa", "hsa 8983711", "r hsa 8983711" ] }, { "record_id": "GLY_000594_1_653", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "oas antiviral", "antiviral response", "oas antiviral response", "the human", "human oligoadenylate", "oligoadenylate synthetase", "family consists", "consists of", "of four", "four proteins", "proteins whose", "whose production", "production is", "is stimulated", "stimulated by", "by interferon", "and oasl.", "oasl. the", "the first", "first three", "three members", "members have", "have the", "the 2'", "2' 5'", "5' oligoadenylate", "synthetase activity", "activity for", "for which", "which the", "the family", "family is", "is named", "sadler aj", "aj &", "& williams", "williams br", "br 2008", "whereas oasl", "oasl is", "is devoid", "devoid of", "of this", "this activity", "activity despite", "despite sharing", "sharing significant", "significant sequence", "sequence similarity", "similarity with", "with the", "the other", "other oas", 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some", ".

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some", "2014 .

some oas", ".

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some", "al. 2014 .

some oas", "2014 .

some oas proteins", ".

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to synthesize", "stranded rna to synthesize 5'", "rna to synthesize 5' triphosphorylated", "to synthesize 5' triphosphorylated 2'", "synthesize 5' triphosphorylated 2' 5'", "5' triphosphorylated 2' 5' oligoadenylates", "2' 5' oligoadenylates 2", "5' oligoadenylates 2 5a", "2 5a from atp", "from atp kerr im", "atp kerr im &", "kerr im & brown re", "im & brown re 1978", "& brown re 1978 .", "brown re 1978 . the", "re 1978 . the 2", "1978 . the 2 5a", ". the 2 5a serve", "the 2 5a serve as", "2 5a serve as chemically", "5a serve as chemically unique", "serve as chemically unique second", "as chemically unique second messengers", "chemically unique second messengers that", "unique second messengers that induce", "second messengers that induce regulated", "messengers that induce regulated rna", "that induce regulated rna decay", "induce regulated rna decay by", "regulated rna decay by activating", "rna decay by activating ribonuclease", "decay by activating ribonuclease l", "activating 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cleaves single", "rnase l cleaves single stranded", "l cleaves single stranded rna", "single stranded rna ssrna", "rna ssrna in", "ssrna in u rich", "u rich sequences typically", "rich sequences typically after", "sequences typically after uu", "typically after uu or ua", "after uu or ua dinucleotides", "uu or ua dinucleotides leaving", "or ua dinucleotides leaving a", "ua dinucleotides leaving a 5'", "dinucleotides leaving a 5' oh", "leaving a 5' oh and", "a 5' oh and 2'", "5' oh and 2' 3'", "oh and 2' 3' cyclic", "and 2' 3' cyclic phosphate", "3' cyclic phosphate floyd", "cyclic phosphate floyd smith", "phosphate floyd smith g", "floyd smith g et al.", "smith g et al. 1981", "et al. 1981 wreschner", "al. 1981 wreschner dh", "1981 wreschner dh et", "dh et al.1981 cooper", "et al.1981 cooper da", "al.1981 cooper da et", "cooper da et al. 2014", "da et al. 2014 .

some", "et al. 2014 .

some oas", "al. 2014 .

some oas proteins", "2014 .

some oas proteins have", ".

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"isoforms. the", "mecp2_e2 isoform", "isoform was", "was cloned", "cloned first", "first and", "and is", "is therefore", "therefore more", "more extensively", "extensively studied.", "studied. the", "isoform is", "is more", "more abundant", "abundant in", "in the", "the brain", "mnatzakanian et", "et al.", "al. 2004", "kriaucionis and", "and bird", "bird 2004", "kaddoum et", "al. 2013", "2013 .", ". mecp2", "mecp2 isoforms", "isoforms show", "show different", "different expression", "expression patterns", "patterns during", "during mouse", "mouse brain", "brain development", "development and", "and in", "in adult", "adult brain", "brain regions", "dragich et", "al. 2007", "olson et", "al. 2014", "2014 .", ". while", "while rett", "syndrome mutations", "mutations mainly", "mainly occur", "occur in", "in exons", "4 of", "of mecp2", "thereby affecting", "affecting both", "both mecp2", "some mutations", "mutations occur", "in exon", "affecting mecp2_e1", "mecp2_e1 only.", "only. no", "no mutations", "mutations have", "have been", "been described", "described in", "gianakopoulos et", "al. 2012", "2012 .", ". knockout", "knockout of", "of mecp2_e1", "isoform in", "in mice", "through a", "a naturally", "naturally occurring", "occurring rett", "syndrome point", "point mutation", "mutation which", "which affects", "affects the", "the first", "first translation", "translation codon", "codon of", "recapitulates rett", "rett like", "like phenotype.", "phenotype. knockout", "of mecp2_e2", "mice does", "does not", "not result", "result in", "in impairment", "impairment of", "of neurologic", "neurologic functions", "yasui et", ". in", "in mecp2", "mecp2 null", "null mice", "transgenic expression", "of either", "either mecp2_e1", "mecp2_e1 or", "or mecp2_e2", "mecp2_e2 prevents", "prevents development", "development of", "like phenotype", "with mecp2_e1", "mecp2_e1 rescuing", "rescuing more", "more rett", "like symptoms", "symptoms than", "than mecp2_e2.", "mecp2_e2. this", "this indicates", "indicates that", "that both", "both splice", "splice variants", "variants can", "can fulfill", "fulfill basic", "basic mecp2", "mecp2 functions", "functions in", "the mouse", "kerr et", ". changes", "changes in", "in gene", "gene expression", "expression upon", "upon over", "over expression", "mecp2_e2 imply", "imply overlapping", "overlapping as", "as well", "well as", "as distinct", "distinct target", "target genes", "orlic milacic", "milacic et", "2014 .

methyl", ".

methyl cpg", "cpg binding", "binding protein", "protein 2", "2 encoded", "by the", "gene binds", "binds to", "to methylated", "methylated cpg", "cpg sequences", "sequences in", "the dna.", "dna. the", "the binding", "binding is", "is not", "not generic", "but is", "is affected", "affected by", "the underlying", "underlying dna", "dna sequence", "yoon et", "al. 2003", "2003 .", "mecp2 binds", "to dna", "dna containing", "containing 5", "5 methylcytosine", "5mc dna", "a dna", "dna modification", "modification associated", "associated with", "with transcriptional", "transcriptional repression", "mellen et", "both in", "the context", "context of", "of cpg", "cpg islands", "islands and", "and outside", "outside of", "chen et", "al. 2015", "2015 .", "in addition", "5 hydroxymethylcytosine", "5hmc dna", "transcriptional activation", "dna as", "as a", "a monomer", "occupying about", "about 11", "11 bp", "bp of", "dna. binding", "binding of", "of one", "one mecp2", "mecp2 molecule", "molecule facilitates", "facilitates binding", "second mecp2", "and therefore", "therefore clustering", "clustering can", "can occur", "occur at", "at target", "target sites.", "sites. mecp2", "mecp2 binding", "binding to", "to chromatin", "chromatin may", "may be", "be facilitated", "facilitated by", "by nucleosome", "nucleosome methylation", "ghosh et", "al. 2010", "2010 .

mecp2", ".

mecp2 was", "was initially", "initially proposed", "proposed to", "to act", "act as", "a generic", "generic repressor", "repressor of", "of gene", "gene transcription.", "transcription. however", "high throughput", "throughput studies", "studies of", "mecp2 induced", "induced changes", "expression in", "in mouse", "mouse hippocampus", "chahrour et", "al. 2008", "and mouse", "mouse and", "and human", "human cell", "cell lines", "indicate that", "that more", "more genes", "genes are", "are up", "up regulated", "regulated than", "than down", "down regulated", "regulated when", "when mecp2", "is overexpressed.", "overexpressed. at", "at least", "least for", "for some", "some genes", "genes directly", "directly upregulated", "upregulated by", "it was", "was shown", "shown that", "that a", "a complex", "complex of", "mecp2 and", "and creb1", "creb1 was", "was involved", "involved in", "in transcriptional", "transcriptional stimulation", "2013 .

mecp2", ".

mecp2 expression", "expression is", "is the", "the highest", "highest in", "in postmitotic", "postmitotic neurons", "neurons compared", "compared to", "to other", "other cell", "cell types", "with mecp2", "mecp2 being", "being almost", "almost as", "as abundant", "abundant as", "as core", "core histones.", "histones. phosphorylation", "phosphorylation of", "mecp2 in", "in response", "response to", "to neuronal", "neuronal activity", "activity regulates", "regulates binding", "mecp2 to", "suggesting that", "that mecp2", "mecp2 may", "may remodel", "remodel chromatin", "chromatin in", "in a", "a neuronal", "activity dependent", "dependent manner.", "manner. the", "the resulting", "resulting changes", "expression would", "would then", "then modulate", "modulate synaptic", "synaptic plasticity", "plasticity and", "and behavior", "reviewed by", "by ebert", "ebert and", "and greenberg", "greenberg 2013", "in human", "human embryonic", "embryonic stem", "stem cell", "cell derived", "derived rett", "syndrome neurons", "is associated", "with a", "a significant", "significant reduction", "reduction in", "in transcription", "transcription of", "of neuronally", "neuronally active", "active genes", "the reduction", "in nascent", "nascent protein", "protein synthesis.", "synthesis. the", "protein synthesis", "synthesis can", "can at", "least in", "in part", "part be", "be attributed", "attributed to", "to the", "the decreased", "decreased activity", "activity of", "the pi3k/akt/mtor", "pi3k/akt/mtor signaling", "signaling pathway.", "pathway. neuronal", "neuronal morphology", "reduced soma", "soma size", "and the", "the level", "level of", "of protein", "synthesis in", "in rett", "rett neurons", "neurons can", "can be", "be ameliorated", "ameliorated by", "by treating", "treating the", "the cells", "cells with", "with growth", "growth factors", "factors which", "which activate", "activate the", "pi3k/akt/mtor cascade", "cascade or", "or by", "by inhibition", "inhibition of", "of pten", "the negative", "negative regulator", "regulator of", "of akt", "akt activation.", "activation. mitochondrial", "mitochondrial gene", "is also", "also downregulated", "downregulated in", "which is", "a reduced", "reduced capacity", "capacity of", "the mitochondrial", "mitochondrial electron", "electron transport", "transport chain", "ricciardi et", "al. 2011", "li et", ". treatment", "treatment of", "mice with", "with igf1", "insulin like", "like growth", "growth factor", "factor 1", "reverses or", "or ameliorates", "ameliorates some", "some rett", "like features", "features such", "such as", "as locomotion", "respiratory difficulties", "difficulties and", "and irregular", "irregular heart", "heart rate", "tropea et", "al. 2009", "2009 .

mecp2", ".

mecp2 regulates", "regulates expression", "of a", "a number", "number of", "of ligands", "ligands and", "and receptors", "receptors involved", "in neuronal", "neuronal development", "and function.", "function. ligands", "ligands regulated", "regulated by", "mecp2 include", "include bdnf", "by li", "li and", "and pozzo", "pozzo miller", "miller 2014", "and khorshidahmad", "khorshidahmad et", "al. 2016", "mcgill et", "al. 2006", "samaco et", "and dll1", "mecp2 also", "also regulates", "regulates transcription", "of genes", "genes involved", "the synthesis", "synthesis of", "the neurotransmitter", "neurotransmitter gaba", "gaba \u2013", "\u2013 gad1", "chao et", "and gad2", "he et", "be involved", "in direct", "direct stimulation", "stimulation of", "of transcription", "transcription from", "from the", "the glud1", "glud1 gene", "gene promoter", "encoding mitochondrial", "mitochondrial glutamate", "glutamate dehydrogenase", "dehydrogenase 1", "which may", "the turnover", "turnover of", "neurotransmitter glutamate", "livide et", ". receptors", "receptors regulated", "include glutamate", "glutamate receptor", "receptor gria2", "qiu et", "nmda receptor", "receptor subunits", "subunits grin2a", "durand et", "and grin2b", "lee et", "opioid receptors", "receptors oprk1", "and oprm1", "hwang et", "plummer et", ". channels/transporters", "channels/transporters regulated", "include trpc3", "and slc2a3", "mecp2 regulates", "of fkbp5", "in trafficking", "trafficking of", "of glucocorticoid", "glucocorticoid receptors", "nuber et", "al. 2005", "urdinguio et", "2008 .", "is implicated", "implicated in", "in regulation", "regulation of", "of expression", "of sema3f", "semaphorin 3f", "mouse olfactory", "olfactory neurons", "degano et", "2009 .", "in zebrafish", "in sensory", "sensory axon", "axon guidance", "guidance by", "by direct", "of sema5b", "sema5b and", "and robo2", "leong et", "may indirectly", "indirectly regulate", "regulate signaling", "signaling by", "by neuronal", "neuronal receptor", "receptor tyrosine", "tyrosine kinases", "kinases by", "by regulating", "regulating transcription", "protein tyrosine", "tyrosine phosphatases", "krishnan et", "and ptpn4", "williamson et", "2015 .

mecp2", "of several", "several transcription", "transcription factors", "factors involved", "in functioning", "functioning of", "the nervous", "nervous system", "as creb1", "and pparg", "mann et", "joss moore", "moore et", "2011 .

mecp2", ".

mecp2 associates", "associates with", "with transcription", "transcription and", "and chromatin", "chromatin remodeling", "remodeling factors", "the hdac1/2", "hdac1/2 containing", "containing sin3a", "sin3a co", "co repressor", "repressor complex", "nan et", "al. 1998", "the ncor/smrt", "ncor/smrt complex", "lyst et", "ebert et", ". there", "there are", "are contradictory", "contradictory reports", "reports on", "on the", "the interaction", "interaction of", "mecp2 with", "with the", "the swi/snf", "swi/snf chromatin", "remodeling complex", "harikrishnan et", "hu et", "2006 .", ". interaction", "the dna", "dna methyltransferase", "methyltransferase dnmt1", "dnmt1 has", "has been", "been reported", "a concomitant", "concomitant increase", "increase in", "in enzymatic", "enzymatic activity", "of dnmt1", "kimura and", "and shiota", "shiota 2003", "2003 .

in", ".

in addition", "addition to", "dna binding", "binding dependent", "dependent regulation", "expression by", "may influence", "influence gene", "by interaction", "interaction with", "with components", "components of", "the drosha", "drosha microprocessor", "microprocessor complex", "complex and", "the consequent", "consequent change", "change in", "the levels", "levels of", "of mature", "mature micrornas", "cheng et", "tsujimura et", "2015 .

increased", ".

increased mecp2", "mecp2 promoter", "promoter methylation", "methylation is", "is observed", "observed in", "both male", "male and", "and female", "female autism", "autism patients", "nagarajan et", ". regulatory", "regulatory elements", "elements that", "that undergo", "undergo methylation", "methylation are", "are found", "found in", "the promoter", "promoter and", "first intron", "intron of", "and their", "their methylation", "methylation was", "shown to", "to regulate", "regulate mecp2", "mecp2 expression", "liyanage et", ". mouse", "mouse mecp2", "to be", "be affected", "by stress", "franklin et", "2010 .

the", ".

the rett", "phenotype of", "mice is", "is reversible", "guy et", "but appropriate", "appropriate levels", "expression need", "need to", "be achieved", "alvarez saavedra", "saavedra et", "2007 .", ". when", "is restored", "restored in", "in astrocytes", "astrocytes of", "amelioration of", "rett symptoms", "symptoms occurs", "involving non", "non cell", "cell autonomous", "autonomous positive", "positive effect", "effect on", "on mutant", "mutant neurons", "neurons and", "and increasing", "increasing level", "the excitatory", "excitatory glutamate", "glutamate transporter", "transporter vglut1", "lioy et", "2011 .", ". microglia", "microglia derived", "derived from", "from mecp2", "mice releases", "releases higher", "higher than", "than normal", "normal levels", "of glutamate", "which has", "has toxic", "toxic effect", "on neurons.", "neurons. increased", "increased glutamate", "glutamate secretion", "secretion may", "be due", "due to", "to increased", "increased levels", "of glutaminase", "in glutamate", "glutamate synthesis", "and increased", "of connexin", "connexin 32", "glutamate release", "null microglia", "maezawa and", "and jin", "jin 2010", "2010 .", ". targeted", "targeted deletion", "deletion of", "mecp2 from", "from sim1", "sim1 expressing", "expressing neurons", "neurons of", "mouse hypothalamus", "hypothalamus recapitulates", "recapitulates some", "syndrome like", "features and", "and highlights", "highlights the", "the role", "role of", "in feeding", "feeding behavior", "behavior and", "and response", "to stress", "fyffe et", "2008 .

mecp2", ".

mecp2 overexpression", "similar to", "to mecp2", "mecp2 duplication", "duplication syndrome", "causes neurologic", "neurologic phenotype", "phenotype similar", "to rett", "collins et", "luikenhuis et", "van esch", "esch et", "saavedra 2007", "the phenotype", "mouse model", "model of", "syndrome in", "adult mice", "reversible when", "expression levels", "levels are", "are corrected", "sztainberg et", "mecp2 is an", "is an x", "an x chromosome", "x chromosome gene", "chromosome gene whose", "gene whose loss", "whose loss of", "loss of function", "of function mutations", "function mutations are", "mutations are an", "are an underlying", "an underlying cause", "underlying cause of", "cause of the", "of the majority", "the majority of", "majority of rett", "of rett syndrome", "rett syndrome cases.", "syndrome cases. the", "cases. the mecp2", "the mecp2 gene", "mecp2 gene locus", "gene locus consists", "locus consists of", "consists of four", "of four exons.", "four exons. both", "exons. both exon", "both exon 1", "exon 1 and", "1 and exon", "and exon 2", "exon 2 contain", "2 contain translation", "contain translation start", "translation start sites.", "start sites. alternative", "sites. alternative splicing", "alternative splicing of", "splicing of the", "of the second", "the second exon", "second exon results", "exon results in", "results in expression", "in expression of", "expression of two", "of two mecp2", "two mecp2 transcript", "mecp2 transcript isoforms", "isoforms mecp2_e1", "mecp2_e1 mecp2b", "mecp2b or mecp2alpha", "mecp2alpha and", "mecp2_e2 mecp2a", "mecp2a or mecp2beta", "or mecp2beta .", "mecp2beta . the", ". the n", "the n terminus", "n terminus of", "terminus of the", "of the mecp2_e1", "the mecp2_e1 isoform", "in which exon", "which exon 2", "exon 2 is", "2 is spliced", "is spliced out", "out is", "is encoded by", "encoded by exon", "by exon 1.", "exon 1. the", "1. the n", "of the mecp2_e2", "the mecp2_e2 isoforms", "isoforms which", "which includes both", "includes both exon", "by exon 2", "2 as", "as the exon", "the exon 2", "exon 2 translation", "2 translation start", "translation start site", "start site is", "site is used.", "is used. exons", "used. exons 3", "exons 3 and", "3 and 4", "and 4 are", "4 are present", "are present in", "present in both", "in both isoforms.", "both isoforms. the", "isoforms. the mecp2_e2", "the mecp2_e2 isoform", "mecp2_e2 isoform was", "isoform was cloned", "was cloned first", "cloned first and", "first and is", "and is therefore", "is therefore more", "therefore more extensively", "more extensively studied.", "extensively studied. the", "studied. the mecp2_e1", "mecp2_e1 isoform is", "isoform is more", "is more abundant", "more abundant in", "abundant in the", "in the brain", "brain mnatzakanian", "mnatzakanian et al.", "et al. 2004", "2004 kriaucionis", "kriaucionis and bird", "and bird 2004", "2004 kaddoum", "kaddoum et al.", "et al. 2013", "al. 2013 .", "2013 . mecp2", ". mecp2 isoforms", "mecp2 isoforms show", "isoforms show different", "show different expression", "different expression patterns", "expression patterns during", "patterns during mouse", "during mouse brain", "mouse brain development", "brain development and", "development and in", "and in adult", "in adult brain", "adult brain regions", "regions dragich", "dragich et al.", "et al. 2007", "2007 olson", "olson et al.", "et al. 2014", "al. 2014 .", "2014 . while", ". while rett", "while rett syndrome", "rett syndrome mutations", "syndrome mutations mainly", "mutations mainly occur", "mainly occur in", "occur in exons", "in exons 3", "and 4 of", "4 of mecp2", "mecp2 thereby", "thereby affecting both", "affecting both mecp2", "both mecp2 isoforms", "isoforms mnatzakanian", "some mutations occur", "mutations occur in", "occur in exon", "in exon 1", "1 affecting", "affecting mecp2_e1 only.", "mecp2_e1 only. no", "only. no mutations", "no mutations have", "mutations have been", "have been described", "been described in", "described in exon", "in exon 2", "2 gianakopoulos", "gianakopoulos et al.", "et al. 2012", "al. 2012 .", "2012 . knockout", ". knockout of", "knockout of mecp2_e1", "of mecp2_e1 isoform", "mecp2_e1 isoform in", "isoform in mice", "mice through", "through a naturally", "a naturally occurring", "naturally occurring rett", "occurring rett syndrome", "rett syndrome point", "syndrome point mutation", "point mutation which", "mutation which affects", "which affects the", "affects the first", "the first translation", "first translation codon", "translation codon of", "codon of mecp2_e1", "mecp2_e1 recapitulates", "recapitulates rett like", "rett like phenotype.", "like phenotype. knockout", "phenotype. knockout of", "knockout of mecp2_e2", "of mecp2_e2 isoform", "mecp2_e2 isoform in", "in mice does", "mice does not", "does not result", "not result in", "result in impairment", "in impairment of", "impairment of neurologic", "of neurologic functions", "functions yasui", "yasui et al.", "2014 . in", ". in mecp2", "in mecp2 null", "mecp2 null mice", "mice transgenic", "transgenic expression of", "expression of either", "of either mecp2_e1", "either mecp2_e1 or", "mecp2_e1 or mecp2_e2", "or mecp2_e2 prevents", "mecp2_e2 prevents development", "prevents development of", "development of rett", "of rett like", "rett like phenotype", "phenotype with", "with mecp2_e1 rescuing", "mecp2_e1 rescuing more", "rescuing more rett", "more rett like", "rett like symptoms", "like symptoms than", "symptoms than mecp2_e2.", "than mecp2_e2. this", "mecp2_e2. this indicates", "this indicates that", "indicates that both", "that both splice", "both splice variants", "splice variants can", "variants can fulfill", "can fulfill basic", "fulfill basic mecp2", "basic mecp2 functions", "mecp2 functions in", "functions in the", "in the mouse", "the mouse brain", "brain kerr", "kerr et al.", "2012 . changes", ". changes in", "changes in gene", "in gene expression", "gene expression upon", "expression upon over", "upon over expression", "over expression of", "or mecp2_e2 imply", "mecp2_e2 imply overlapping", "imply overlapping as", "overlapping as well", "as well as", "well as distinct", "as distinct target", "distinct target genes", "genes orlic", "orlic milacic et", "milacic et al.", "al. 2014 .

methyl", "2014 .

methyl cpg", ".

methyl cpg binding", "cpg binding protein", "binding protein 2", "protein 2 encoded", "2 encoded by", "encoded by the", "by the mecp2", "mecp2 gene binds", "gene binds to", "binds to methylated", "to methylated cpg", "methylated cpg sequences", "cpg sequences in", "sequences in the", "in the dna.", "the dna. the", "dna. the binding", "the binding is", "binding is not", "is not generic", "generic however", "however but", "but is affected", "is affected by", "affected by the", "by the underlying", "the underlying dna", "underlying dna sequence", "sequence yoon", "yoon et al.", "et al. 2003", "al. 2003 .", "2003 . mecp2", ". mecp2 binds", "mecp2 binds to", "binds to dna", "to dna containing", "dna containing 5", "containing 5 methylcytosine", "methylcytosine 5mc", "a dna modification", "dna modification associated", "modification associated with", "associated with transcriptional", "with transcriptional repression", "repression mellen", "mellen et al.", "both in the", "in the context", "the context of", "context of cpg", "of cpg islands", "cpg islands and", "islands and outside", "and outside of", "outside of cpg", "islands chen", "chen et al.", "et al. 2015", "al. 2015 .", "2015 . in", ". in addition", "addition mecp2", "containing 5 hydroxymethylcytosine", "hydroxymethylcytosine 5hmc", "with transcriptional activation", "activation mellen", "2012 . mecp2", "to dna as", "dna as a", "as a monomer", "monomer occupying", "occupying about 11", "about 11 bp", "11 bp of", "bp of the", "of the dna.", "the dna. binding", "dna. binding of", "binding of one", "of one mecp2", "one mecp2 molecule", "mecp2 molecule facilitates", "molecule facilitates binding", "facilitates binding of", "binding of the", "the second mecp2", "second mecp2 molecule", "molecule and", "and therefore clustering", "therefore clustering can", "clustering can occur", "can occur at", "occur at target", "at target sites.", "target sites. mecp2", "sites. mecp2 binding", "mecp2 binding to", "binding to chromatin", "to chromatin may", "chromatin may be", "may be facilitated", "be facilitated by", "facilitated by nucleosome", "by nucleosome methylation", "methylation ghosh", "ghosh et al.", "et al. 2010", "al. 2010 .

mecp2", "2010 .

mecp2 was", ".

mecp2 was initially", "was initially proposed", "initially proposed to", "proposed to act", "to act as", "act as a", "as a generic", "a generic repressor", "generic repressor of", "repressor of gene", "of gene transcription.", "gene transcription. however", "however high", "high throughput studies", "throughput studies of", "studies of mecp2", "of mecp2 induced", "mecp2 induced changes", "induced changes in", "gene expression in", "expression in mouse", "in mouse hippocampus", "hippocampus chahrour", "chahrour et al.", "et al. 2008", "and mouse and", "mouse and human", "and human cell", "human cell lines", "lines orlic", "2014 indicate", "indicate that more", "that more genes", "more genes are", "genes are up", "are up regulated", "up regulated than", "regulated than down", "than down regulated", "down regulated when", "regulated when mecp2", "when mecp2 is", "mecp2 is overexpressed.", "is overexpressed. at", "overexpressed. at least", "at least for", "least for some", "for some genes", "some genes directly", "genes directly upregulated", "directly upregulated by", "upregulated by mecp2", "mecp2 it", "it was shown", "was shown that", "shown that a", "that a complex", "a complex of", "complex of mecp2", "of mecp2 and", "mecp2 and creb1", "and creb1 was", "creb1 was involved", "was involved in", "involved in transcriptional", "in transcriptional stimulation", "stimulation chahrour", "2008 chen", "al. 2013 .

mecp2", "2013 .

mecp2 expression", ".

mecp2 expression is", "expression is the", "is the highest", "the highest in", "highest in postmitotic", "in postmitotic neurons", "postmitotic neurons compared", "neurons compared to", "compared to other", "to other cell", "other cell types", "types with", "with mecp2 being", "mecp2 being almost", "being almost as", "almost as abundant", "as abundant as", "abundant as core", "as core histones.", "core histones. phosphorylation", "histones. phosphorylation of", "phosphorylation of mecp2", "of mecp2 in", "mecp2 in response", "in response to", "response to neuronal", "to neuronal activity", "neuronal activity regulates", "activity regulates binding", "regulates binding of", "binding of mecp2", "of mecp2 to", "mecp2 to dna", "dna suggesting", "suggesting that mecp2", "that mecp2 may", "mecp2 may remodel", "may remodel chromatin", "remodel chromatin in", "chromatin in a", "in a neuronal", "a neuronal activity", "neuronal activity dependent", "activity dependent manner.", "dependent manner. the", "manner. the resulting", "the resulting changes", "resulting changes in", "gene expression would", "expression would then", "would then modulate", "then modulate synaptic", "modulate synaptic plasticity", "synaptic plasticity and", "plasticity and behavior", "behavior reviewed", "reviewed by ebert", "by ebert and", "ebert and greenberg", "and greenberg 2013", "greenberg 2013 .", "2013 . in", ". in human", "in human embryonic", "human embryonic stem", "embryonic stem cell", "stem cell derived", "cell derived rett", "derived rett syndrome", "rett syndrome neurons", "neurons loss", "loss of mecp2", "of mecp2 is", "mecp2 is associated", "is associated with", "associated with a", "with a significant", "a significant reduction", "significant reduction in", "reduction in transcription", "in transcription of", "transcription of neuronally", "of neuronally active", "neuronally active genes", "genes as", "well as the", "as the reduction", "the reduction in", "reduction in nascent", "in nascent protein", "nascent protein synthesis.", "protein synthesis. the", "synthesis. the reduction", "nascent protein synthesis", "protein synthesis can", "synthesis can at", "can at least", "at least in", "least in part", "in part be", "part be attributed", "be attributed to", "attributed to the", "to the decreased", "the decreased activity", "decreased activity of", "activity of the", "of the pi3k/akt/mtor", "the pi3k/akt/mtor signaling", "pi3k/akt/mtor signaling pathway.", "signaling pathway. neuronal", "pathway. neuronal morphology", "morphology reduced", "reduced soma size", "size and", "and the level", "the level of", "level of protein", "of protein synthesis", "protein synthesis in", "synthesis in rett", "in rett neurons", "rett neurons can", "neurons can be", "can be ameliorated", "be ameliorated by", "ameliorated by treating", "by treating the", "treating the cells", "the cells with", "cells with growth", "with growth factors", "growth factors which", "factors which activate", "which activate the", "activate the pi3k/akt/mtor", "the pi3k/akt/mtor cascade", "pi3k/akt/mtor cascade or", "cascade or by", "or by inhibition", "by inhibition of", "inhibition of pten", "pten the", "the negative regulator", "negative regulator of", "regulator of akt", "of akt activation.", "akt activation. mitochondrial", "activation. mitochondrial gene", "mitochondrial gene expression", "gene expression is", "expression is also", "is also downregulated", "also downregulated in", "downregulated in rett", "neurons which", "which is associated", "with a reduced", "a reduced capacity", "reduced capacity of", "capacity of the", "of the mitochondrial", "the mitochondrial electron", "mitochondrial electron transport", "electron transport chain", "chain ricciardi", "ricciardi et al.", "et al. 2011", "2011 li", "li et al.", "2013 . treatment", ". treatment of", "treatment of mecp2", "of mecp2 null", "null mice with", "mice with igf1", "igf1 insulin", "insulin like growth", "like growth factor", "growth factor 1", "1 reverses", "reverses or ameliorates", "or ameliorates some", "ameliorates some rett", "some rett like", "rett like features", "like features such", "features such as", "such as locomotion", "locomotion respiratory", "respiratory difficulties and", "difficulties and irregular", "and irregular heart", "irregular heart rate", "rate tropea", "tropea et al.", "et al. 2009", "al. 2009 .

mecp2", "2009 .

mecp2 regulates", ".

mecp2 regulates expression", "regulates expression of", "expression of a", "of a number", "a number of", "number of ligands", "of ligands and", "ligands and receptors", "and receptors involved", "receptors involved in", "involved in neuronal", "in neuronal development", "neuronal development and", "development and function.", "and function. ligands", "function. ligands regulated", "ligands regulated by", "regulated by mecp2", "by mecp2 include", "mecp2 include bdnf", "bdnf reviewed", "reviewed by li", "by li and", "li and pozzo", "and pozzo miller", "pozzo miller 2014", "2014 and", "and khorshidahmad et", "khorshidahmad et al.", "et al. 2016", "crh mcgill", "mcgill et al.", "et al. 2006", "2006 samaco", "samaco et al.", "sst somatostatin", "dll1 li", "2014 . mecp2", ". mecp2 also", "mecp2 also regulates", "also regulates transcription", "regulates transcription of", "transcription of genes", "of genes involved", "genes involved in", "involved in the", "in the synthesis", "the synthesis of", "synthesis of the", "of the neurotransmitter", "the neurotransmitter gaba", "neurotransmitter gaba \u2013", "gaba \u2013 gad1", "gad1 chao", "chao et al.", "2010 and", "gad2 chao", "2010 he", "he et al.", ". mecp2 may", "mecp2 may be", "may be involved", "be involved in", "involved in direct", "in direct stimulation", "direct stimulation of", "stimulation of transcription", "of transcription from", "transcription from the", "from the glud1", "the glud1 gene", "glud1 gene promoter", "promoter encoding", "encoding mitochondrial glutamate", "mitochondrial glutamate dehydrogenase", "glutamate dehydrogenase 1", "1 which", "which may be", "in the turnover", "the turnover of", "turnover of the", "the neurotransmitter glutamate", "glutamate livide", "livide et al.", "2015 . receptors", ". receptors regulated", "receptors regulated by", "mecp2 include glutamate", "include glutamate receptor", "glutamate receptor gria2", "gria2 qiu", "qiu et al.", "nmda receptor subunits", "receptor subunits grin2a", "grin2a durand", "durand et al.", "2012 and", "grin2b lee", "lee et al.", "opioid receptors oprk1", "oprk1 chahrour", "2008 and", "oprm1 hwang", "hwang et al.", "2009 hwang", "2010 samaco", "gprin1 chahrour", "met plummer", "plummer et al.", "notch1 li", "2014 . channels/transporters", ". channels/transporters regulated", "channels/transporters regulated by", "mecp2 include trpc3", "trpc3 li", "slc2a3 chen", ". mecp2 regulates", "mecp2 regulates transcription", "transcription of fkbp5", "fkbp5 involved", "involved in trafficking", "in trafficking of", "trafficking of glucocorticoid", "of glucocorticoid receptors", "receptors nuber", "nuber et al.", "et al. 2005", "2005 urdinguio", "urdinguio et al.", "al. 2008 .", "2008 . mecp2", ". mecp2 is", "mecp2 is implicated", "is implicated in", "implicated in regulation", "in regulation of", "regulation of expression", "of expression of", "expression of sema3f", "sema3f semaphorin", "3f in", "in mouse olfactory", "mouse olfactory neurons", "neurons degano", "degano et al.", "al. 2009 .", "2009 . in", ". in zebrafish", "zebrafish mecp2", "implicated in sensory", "in sensory axon", "sensory axon guidance", "axon guidance by", "guidance by direct", "by direct stimulation", "of transcription of", "transcription of sema5b", "of sema5b and", "sema5b and robo2", "robo2 leong", "leong et al.", "2015 . mecp2", "mecp2 may indirectly", "may indirectly regulate", "indirectly regulate signaling", "regulate signaling by", "signaling by neuronal", "by neuronal receptor", "neuronal receptor tyrosine", "receptor tyrosine kinases", "tyrosine kinases by", "kinases by regulating", "by regulating transcription", "regulating transcription of", "transcription of protein", "of protein tyrosine", "protein tyrosine phosphatases", "phosphatases ptpn1", "ptpn1 krishnan", "krishnan et al.", "2015 and", "ptpn4 williamson", "williamson et al.", "al. 2015 .

mecp2", "2015 .

mecp2 regulates", ".

mecp2 regulates transcription", "transcription of several", "of several transcription", "several transcription factors", "transcription factors involved", "factors involved in", "involved in functioning", "in functioning of", "functioning of the", "of the nervous", "the nervous system", "system such", "such as creb1", "creb1 mef2c", "mef2c rbfox1", "rbfox1 chahrour", "pparg mann", "mann et al.", "2010 joss", "joss moore et", "moore et al.", "al. 2011 .

mecp2", "2011 .

mecp2 associates", ".

mecp2 associates with", "associates with transcription", "with transcription and", "transcription and chromatin", "and chromatin remodeling", "chromatin remodeling factors", "factors such", "creb1 chahrour", "the hdac1/2 containing", "hdac1/2 containing sin3a", "containing sin3a co", "sin3a co repressor", "co repressor complex", "complex nan", "nan et al.", "et al. 1998", "and the ncor/smrt", "the ncor/smrt complex", "complex lyst", "lyst et al.", "2013 ebert", "ebert et al.", "2013 . there", ". there are", "there are contradictory", "are contradictory reports", "contradictory reports on", "reports on the", "on the interaction", "the interaction of", "interaction of mecp2", "of mecp2 with", "mecp2 with the", "with the swi/snf", "the swi/snf chromatin", "swi/snf chromatin remodeling", "chromatin remodeling complex", "complex harikrishnan", "harikrishnan et al.", "2005 hu", "hu et al.", "al. 2006 .", "2006 . interaction", ". interaction of", "with the dna", "the dna methyltransferase", "dna methyltransferase dnmt1", "methyltransferase dnmt1 has", "dnmt1 has been", "has been reported", "reported with", "with a concomitant", "a concomitant increase", "concomitant increase in", "increase in enzymatic", "in enzymatic activity", "enzymatic activity of", "activity of dnmt1", "dnmt1 kimura", "kimura and shiota", "and shiota 2003", "shiota 2003 .

in", "2003 .

in addition", ".

in addition to", "addition to dna", "to dna binding", "dna binding dependent", "binding dependent regulation", "dependent regulation of", "regulation of gene", "of gene expression", "gene expression by", "expression by mecp2", "mecp2 mecp2", "mecp2 may influence", "may influence gene", "influence gene expression", "expression by interaction", "by interaction with", "interaction with components", "with components of", "components of the", "of the drosha", "the drosha microprocessor", "drosha microprocessor complex", "microprocessor complex and", "complex and the", "and the consequent", "the consequent change", "consequent change in", "change in the", "in the levels", "the levels of", "levels of mature", "of mature micrornas", "micrornas cheng", "cheng et al.", "2014 tsujimura", "tsujimura et al.", "al. 2015 .

increased", "2015 .

increased mecp2", ".

increased mecp2 promoter", "mecp2 promoter methylation", "promoter methylation is", "methylation is observed", "is observed in", "observed in both", "in both male", "both male and", "male and female", "and female autism", "female autism patients", "patients nagarajan", "nagarajan et al.", "2008 . regulatory", ". regulatory elements", "regulatory elements that", "elements that undergo", "that undergo methylation", "undergo methylation are", "methylation are found", "are found in", "found in the", "in the promoter", "the promoter and", "promoter and the", "and the first", "the first intron", "first intron of", "intron of mecp2", "mecp2 and their", "and their methylation", "their methylation was", "methylation was shown", "was shown to", "shown to regulate", "to regulate mecp2", "regulate mecp2 expression", "mecp2 expression in", "expression in mice", "mice liyanage", "liyanage et al.", "2013 . mouse", ". mouse mecp2", "mouse mecp2 promoter", "promoter methylation was", "shown to be", "to be affected", "be affected by", "affected by stress", "stress franklin", "franklin et al.", "al. 2010 .

the", "2010 .

the rett", ".

the rett like", "like phenotype of", "phenotype of mecp2", "null mice is", "mice is reversible", "reversible guy", "guy et al.", "but appropriate levels", "appropriate levels of", "levels of mecp2", "of mecp2 expression", "mecp2 expression need", "expression need to", "need to be", "to be achieved", "achieved alvarez", "alvarez saavedra et", "saavedra et al.", "al. 2007 .", "2007 . when", ". when mecp2", "when mecp2 expression", "mecp2 expression is", "expression is restored", "is restored in", "restored in astrocytes", "in astrocytes of", "astrocytes of mecp2", "mice amelioration", "amelioration of rett", "of rett symptoms", "rett symptoms occurs", "occurs involving", "involving non cell", "non cell autonomous", "cell autonomous positive", "autonomous positive effect", "positive effect on", "effect on mutant", "on mutant neurons", "mutant neurons and", "neurons and increasing", "and increasing level", "increasing level of", "level of the", "of the excitatory", "the excitatory glutamate", "excitatory glutamate transporter", "glutamate transporter vglut1", "vglut1 lioy", "lioy et al.", "al. 2011 .", "2011 . microglia", ". microglia derived", "microglia derived from", "derived from mecp2", "from mecp2 null", "null mice releases", "mice releases higher", "releases higher than", "higher than normal", "than normal levels", "normal levels of", "levels of glutamate", "glutamate which", "which has toxic", "has toxic effect", "toxic effect on", "effect on neurons.", "on neurons. increased", "neurons. increased glutamate", "increased glutamate secretion", "glutamate secretion may", "secretion may be", "may be due", "be due to", "due to increased", "to increased levels", "increased levels of", "levels of glutaminase", "glutaminase gls", "involved in glutamate", "in glutamate synthesis", "synthesis and", "and increased levels", "levels of connexin", "of connexin 32", "32 gjb1", "in glutamate release", "release in", "mecp2 null microglia", "microglia maezawa", "maezawa and jin", "and jin 2010", "jin 2010 .", "2010 . targeted", ". targeted deletion", "targeted deletion of", "deletion of mecp2", "of mecp2 from", "mecp2 from sim1", "from sim1 expressing", "sim1 expressing neurons", "expressing neurons of", "neurons of the", "of the mouse", "the mouse hypothalamus", "mouse hypothalamus recapitulates", "hypothalamus recapitulates some", "recapitulates some rett", "some rett syndrome", "rett syndrome like", "syndrome like features", "like features and", "features and highlights", "and highlights the", "highlights the role", "the role of", "role of mecp2", "mecp2 in feeding", "in feeding behavior", "feeding behavior and", "behavior and response", "and response to", "response to stress", "stress fyffe", "fyffe et al.", "al. 2008 .

mecp2", "2008 .

mecp2 overexpression", "overexpression similar", "similar to mecp2", "to mecp2 duplication", "mecp2 duplication syndrome", "syndrome causes", "causes neurologic phenotype", "neurologic phenotype similar", "phenotype similar to", "similar to rett", "rett collins", "collins et al.", "2004 luikenhuis", "luikenhuis et al.", "2004 van", "van esch et", "esch et al.", "2005 alvarez", "alvarez saavedra 2007", "2007 van", "2012 . the", ". the phenotype", "the phenotype of", "phenotype of the", "the mouse model", "mouse model of", "model of the", "of the mecp2", "the mecp2 duplication", "duplication syndrome in", "syndrome in adult", "in adult mice", "adult mice is", "is reversible when", "reversible when mecp2", "mecp2 expression levels", "expression levels are", "levels are corrected", "corrected sztainberg", "sztainberg et al.", "mecp2 is an x", "is an x chromosome", "an x chromosome gene", "x chromosome gene whose", "chromosome gene whose loss", "gene whose loss of", "whose loss of function", "loss of function mutations", "of function mutations are", "function mutations are an", "mutations are an underlying", "are an underlying cause", "an underlying cause of", "underlying cause of the", "cause of the majority", "of the majority of", "the majority of rett", "majority of rett syndrome", "of rett syndrome cases.", "rett syndrome cases. the", "syndrome cases. the mecp2", "cases. the mecp2 gene", "the mecp2 gene locus", "mecp2 gene locus consists", "gene locus consists of", "locus consists of four", "consists of four exons.", "of four exons. both", "four exons. both exon", "exons. both exon 1", "both exon 1 and", "exon 1 and exon", "1 and exon 2", "and exon 2 contain", "exon 2 contain translation", "2 contain translation start", "contain translation start sites.", "translation start sites. alternative", "start sites. alternative splicing", "sites. alternative splicing of", "alternative splicing of the", "splicing of the second", "of the second exon", "the second exon results", "second exon results in", "exon results in expression", "results in expression of", "in expression of two", "expression of two mecp2", "of two mecp2 transcript", "two mecp2 transcript isoforms", "transcript isoforms mecp2_e1", "mecp2_e1 mecp2b or", "or mecp2alpha and", "mecp2alpha and mecp2_e2", "and mecp2_e2 mecp2a", "mecp2_e2 mecp2a or", "mecp2a or mecp2beta .", "or mecp2beta . the", "mecp2beta . the n", ". the n terminus", "the n terminus of", "n terminus of the", "terminus of the mecp2_e1", "of the mecp2_e1 isoform", "isoform in which", "in which exon 2", "which exon 2 is", "exon 2 is spliced", "2 is spliced out", "spliced out is", "out is encoded", "is encoded by exon", "encoded by exon 1.", "by exon 1. the", "exon 1. the n", "1. the n terminus", "terminus of the mecp2_e2", "of the mecp2_e2 isoforms", "mecp2_e2 isoforms which", "isoforms which includes", "which includes both exon", "includes both exon 1", "2 is encoded", "encoded by exon 2", "exon 2 as", "2 as the", "as the exon 2", "the exon 2 translation", "exon 2 translation start", "2 translation start site", "translation start site is", "start site is used.", "site is used. exons", "is used. exons 3", "used. exons 3 and", "exons 3 and 4", "3 and 4 are", "and 4 are present", "4 are present in", "are present in both", "present in both isoforms.", "in both isoforms. the", "both isoforms. the mecp2_e2", "isoforms. the mecp2_e2 isoform", "the mecp2_e2 isoform was", "mecp2_e2 isoform was cloned", "isoform was cloned first", "was cloned first and", "cloned first and is", "first and is therefore", "and is therefore more", "is therefore more extensively", "therefore more extensively studied.", "more extensively studied. the", "extensively studied. the mecp2_e1", "studied. the mecp2_e1 isoform", "the mecp2_e1 isoform is", "mecp2_e1 isoform is more", "isoform is more abundant", "is more abundant in", "more abundant in the", "abundant in the brain", "the brain mnatzakanian", "brain mnatzakanian et", "mnatzakanian et al. 2004", "al. 2004 kriaucionis", "2004 kriaucionis and", "kriaucionis and bird 2004", "bird 2004 kaddoum", "2004 kaddoum et", "kaddoum et al. 2013", "et al. 2013 .", "al. 2013 . mecp2", "2013 . mecp2 isoforms", ". mecp2 isoforms show", "mecp2 isoforms show different", "isoforms show different expression", "show different expression patterns", "different expression patterns during", "expression patterns during mouse", "patterns during mouse brain", "during mouse brain development", "mouse brain development and", "brain development and in", "development and in adult", "and in adult brain", "in adult brain regions", "brain regions dragich", "regions dragich et", "dragich et al. 2007", "al. 2007 olson", "2007 olson et", "olson et al. 2014", "et al. 2014 .", "al. 2014 . while", "2014 . while rett", ". while rett syndrome", "while rett syndrome mutations", "rett syndrome mutations mainly", "syndrome mutations mainly occur", "mutations mainly occur in", "mainly occur in exons", "occur in exons 3", "in exons 3 and", "3 and 4 of", "and 4 of mecp2", "of mecp2 thereby", "mecp2 thereby affecting", "thereby affecting both mecp2", "affecting both mecp2 isoforms", "mecp2 isoforms mnatzakanian", "isoforms mnatzakanian et", "2004 some", "some mutations occur in", "mutations occur in exon", "occur in exon 1", "exon 1 affecting", "1 affecting mecp2_e1", "affecting mecp2_e1 only. no", "mecp2_e1 only. no mutations", "only. no mutations have", "no mutations have been", "mutations have been described", "have been described in", "been described in exon", "described in exon 2", "exon 2 gianakopoulos", "2 gianakopoulos et", "gianakopoulos et al. 2012", "et al. 2012 .", "al. 2012 . knockout", "2012 . knockout of", ". knockout of mecp2_e1", "knockout of mecp2_e1 isoform", "of mecp2_e1 isoform in", "mecp2_e1 isoform in mice", "in mice through", "mice through a", "through a naturally occurring", "a naturally occurring rett", "naturally occurring rett syndrome", "occurring rett syndrome point", "rett syndrome point mutation", "syndrome point mutation which", "point mutation which affects", "mutation which affects the", "which affects the first", "affects the first translation", "the first translation codon", "first translation codon of", "translation codon of mecp2_e1", "of mecp2_e1 recapitulates", "mecp2_e1 recapitulates rett", "recapitulates rett like phenotype.", "rett like phenotype. knockout", "like phenotype. knockout of", "phenotype. knockout of mecp2_e2", "knockout of mecp2_e2 isoform", "of mecp2_e2 isoform in", "mecp2_e2 isoform in mice", "isoform in mice does", "in mice does not", "mice does not result", "does not result in", "not result in impairment", "result in impairment of", "in impairment of neurologic", "impairment of neurologic functions", "neurologic functions yasui", "functions yasui et", "yasui et al. 2014", "al. 2014 . in", "2014 . in mecp2", ". in mecp2 null", "in mecp2 null mice", "null mice transgenic", "mice transgenic expression", "transgenic expression of either", "expression of either mecp2_e1", "of either mecp2_e1 or", "either mecp2_e1 or mecp2_e2", "mecp2_e1 or mecp2_e2 prevents", "or mecp2_e2 prevents development", "mecp2_e2 prevents development of", "prevents development of rett", "development of rett like", "of rett like phenotype", "like phenotype with", "phenotype with mecp2_e1", "with mecp2_e1 rescuing more", "mecp2_e1 rescuing more rett", "rescuing more rett like", "more rett like symptoms", "rett like symptoms than", "like symptoms than mecp2_e2.", "symptoms than mecp2_e2. this", "than mecp2_e2. this indicates", "mecp2_e2. this indicates that", "this indicates that both", "indicates that both splice", "that both splice variants", "both splice variants can", "splice variants can fulfill", "variants can fulfill basic", "can fulfill basic mecp2", "fulfill basic mecp2 functions", "basic mecp2 functions in", "mecp2 functions in the", "functions in the mouse", "in the mouse brain", "mouse brain kerr", "brain kerr et", "kerr et al. 2012", "al. 2012 . changes", "2012 . changes in", ". changes in gene", "changes in gene expression", "in gene expression upon", "gene expression upon over", "expression upon over expression", "upon over expression of", "over expression of either", "mecp2_e1 or mecp2_e2 imply", "or mecp2_e2 imply overlapping", "mecp2_e2 imply overlapping as", "imply overlapping as well", "overlapping as well as", "as well as distinct", "well as distinct target", "as distinct target genes", "target genes orlic", "genes orlic milacic", "orlic milacic et al.", "milacic et al. 2014", "et al. 2014 .

methyl", "al. 2014 .

methyl cpg", "2014 .

methyl cpg binding", ".

methyl cpg binding protein", "cpg binding protein 2", "binding protein 2 encoded", "protein 2 encoded by", "2 encoded by the", "encoded by the mecp2", "by the mecp2 gene", "the mecp2 gene binds", "mecp2 gene binds to", "gene binds to methylated", "binds to methylated cpg", "to methylated cpg sequences", "methylated cpg sequences in", "cpg sequences in the", "sequences in the dna.", "in the dna. the", "the dna. the binding", "dna. the binding is", "the binding is not", "binding is not generic", "not generic however", "however but is", "but is affected by", "is affected by the", "affected by the underlying", "by the underlying dna", "the underlying dna sequence", "dna sequence yoon", "sequence yoon et", "yoon et al. 2003", "et al. 2003 .", "al. 2003 . mecp2", "2003 . mecp2 binds", ". mecp2 binds to", "mecp2 binds to dna", "binds to dna containing", "to dna containing 5", "dna containing 5 methylcytosine", "5 methylcytosine 5mc", "methylcytosine 5mc dna", "dna a", "a dna modification associated", "dna modification associated with", "modification associated with transcriptional", "associated with transcriptional repression", "transcriptional repression mellen", "repression mellen et", "mellen et al. 2012", "2012 both", "both in the context", "in the context of", "the context of cpg", "context of cpg islands", "of cpg islands and", "cpg islands and outside", "islands and outside of", "and outside of cpg", "outside of cpg islands", "cpg islands chen", "islands chen et", "chen et al. 2015", "et al. 2015 .", "al. 2015 . in", "2015 . in addition", "in addition mecp2", "addition mecp2 binds", "dna containing 5 hydroxymethylcytosine", "5 hydroxymethylcytosine 5hmc", "hydroxymethylcytosine 5hmc dna", "associated with transcriptional activation", "transcriptional activation mellen", "activation mellen et", "al. 2012 . mecp2", "2012 . mecp2 binds", "binds to dna as", "to dna as a", "dna as a monomer", "a monomer occupying", "monomer occupying about", "occupying about 11 bp", "about 11 bp of", "11 bp of the", "bp of the dna.", "of the dna. binding", "the dna. binding of", "dna. binding of one", "binding of one mecp2", "of one mecp2 molecule", "one mecp2 molecule facilitates", "mecp2 molecule facilitates binding", "molecule facilitates binding of", "facilitates binding of the", "binding of the second", "of the second mecp2", "the second mecp2 molecule", "mecp2 molecule and", "molecule and therefore", "and therefore clustering can", "therefore clustering can occur", "clustering can occur at", "can occur at target", "occur at target sites.", "at target sites. mecp2", "target sites. mecp2 binding", "sites. mecp2 binding to", "mecp2 binding to chromatin", "binding to chromatin may", "to chromatin may be", "chromatin may be facilitated", "may be facilitated by", "be facilitated by nucleosome", "facilitated by nucleosome methylation", "nucleosome methylation ghosh", "methylation ghosh et", "ghosh et al. 2010", "et al. 2010 .

mecp2", "al. 2010 .

mecp2 was", "2010 .

mecp2 was initially", ".

mecp2 was initially proposed", "was initially proposed to", "initially proposed to act", "proposed to act as", "to act as a", "act as a generic", "as a generic repressor", "a generic repressor of", "generic repressor of gene", "repressor of gene transcription.", "of gene transcription. however", "transcription. however high", "however high throughput", "high throughput studies of", "throughput studies of mecp2", "studies of mecp2 induced", "of mecp2 induced changes", "mecp2 induced changes in", "induced changes in gene", "in gene expression in", "gene expression in mouse", "expression in mouse hippocampus", "mouse hippocampus chahrour", "hippocampus chahrour et", "chahrour et al. 2008", "and mouse and human", "mouse and human cell", "and human cell lines", "cell lines orlic", "lines orlic milacic", "al. 2014 indicate", "2014 indicate that", "indicate that more genes", "that more genes are", "more genes are up", "genes are up regulated", "are up regulated than", "up regulated than down", "regulated than down regulated", "than down regulated when", "down regulated when mecp2", "regulated when mecp2 is", "when mecp2 is overexpressed.", "mecp2 is overexpressed. at", "is overexpressed. at least", "overexpressed. at least for", "at least for some", "least for some genes", "for some genes directly", "some genes directly upregulated", "genes directly upregulated by", "directly upregulated by mecp2", "by mecp2 it", "mecp2 it was", "it was shown that", "was shown that a", "shown that a complex", "that a complex of", "a complex of mecp2", "complex of mecp2 and", "of mecp2 and creb1", "mecp2 and creb1 was", "and creb1 was involved", "creb1 was involved in", "was involved in transcriptional", "involved in transcriptional stimulation", "transcriptional stimulation chahrour", "stimulation chahrour et", "al. 2008 chen", "2008 chen et", "chen et al. 2013", "et al. 2013 .

mecp2", "al. 2013 .

mecp2 expression", "2013 .

mecp2 expression is", ".

mecp2 expression is the", "expression is the highest", "is the highest in", "the highest in postmitotic", "highest in postmitotic neurons", "in postmitotic neurons compared", "postmitotic neurons compared to", "neurons compared to other", "compared to other cell", "to other cell types", "cell types with", "types with mecp2", "with mecp2 being almost", "mecp2 being almost as", "being almost as abundant", "almost as abundant as", "as abundant as core", "abundant as core histones.", "as core histones. phosphorylation", "core histones. phosphorylation of", "histones. phosphorylation of mecp2", "phosphorylation of mecp2 in", "of mecp2 in response", "mecp2 in response to", "in response to neuronal", "response to neuronal activity", "to neuronal activity regulates", "neuronal activity regulates binding", "activity regulates binding of", "regulates binding of mecp2", "binding of mecp2 to", "of mecp2 to dna", "to dna suggesting", "dna suggesting that", "suggesting that mecp2 may", "that mecp2 may remodel", "mecp2 may remodel chromatin", "may remodel chromatin in", "remodel chromatin in a", "chromatin in a neuronal", "in a neuronal activity", "a neuronal activity dependent", "neuronal activity dependent manner.", "activity dependent manner. the", "dependent manner. the resulting", "manner. the resulting changes", "the resulting changes in", "resulting changes in gene", "in gene expression would", "gene expression would then", "expression would then modulate", "would then modulate synaptic", "then modulate synaptic plasticity", "modulate synaptic plasticity and", "synaptic plasticity and behavior", "and behavior reviewed", "behavior reviewed by", "reviewed by ebert and", "by ebert and greenberg", "ebert and greenberg 2013", "and greenberg 2013 .", "greenberg 2013 . in", "2013 . in human", ". in human embryonic", "in human embryonic stem", "human embryonic stem cell", "embryonic stem cell derived", "stem cell derived rett", "cell derived rett syndrome", "derived rett syndrome neurons", "syndrome neurons loss", "neurons loss of", "loss of mecp2 is", "of mecp2 is associated", "mecp2 is associated with", "is associated with a", "associated with a significant", "with a significant reduction", "a significant reduction in", "significant reduction in transcription", "reduction in transcription of", "in transcription of neuronally", "transcription of neuronally active", "of neuronally active genes", "active genes as", "genes as well", "as well as the", "well as the reduction", "as the reduction in", "the reduction in nascent", "reduction in nascent protein", "in nascent protein synthesis.", "nascent protein synthesis. the", "protein synthesis. the reduction", "synthesis. the reduction in", "in nascent protein synthesis", "nascent protein synthesis can", "protein synthesis can at", "synthesis can at least", "can at least in", "at least in part", "least in part be", "in part be attributed", "part be attributed to", "be attributed to the", "attributed to the decreased", "to the decreased activity", "the decreased activity of", "decreased activity of the", "activity of the pi3k/akt/mtor", "of the pi3k/akt/mtor signaling", "the pi3k/akt/mtor signaling pathway.", "pi3k/akt/mtor signaling pathway. neuronal", "signaling pathway. neuronal morphology", "neuronal morphology reduced", "morphology reduced soma", "soma size and", "size and the", "and the level of", "the level of protein", "level of protein synthesis", "of protein synthesis in", "protein synthesis in rett", "synthesis in rett neurons", "in rett neurons can", "rett neurons can be", "neurons can be ameliorated", "can be ameliorated by", "be ameliorated by treating", "ameliorated by treating the", "by treating the cells", "treating the cells with", "the cells with growth", "cells with growth factors", "with growth factors which", "growth factors which activate", "factors which activate the", "which activate the pi3k/akt/mtor", "activate the pi3k/akt/mtor cascade", "the pi3k/akt/mtor cascade or", "pi3k/akt/mtor cascade or by", "cascade or by inhibition", "or by inhibition of", "by inhibition of pten", "of pten the", "pten the negative", "the negative regulator of", "negative regulator of akt", "regulator of akt activation.", "of akt activation. mitochondrial", "akt activation. mitochondrial gene", "activation. mitochondrial gene expression", "mitochondrial gene expression is", "gene expression is also", "expression is also downregulated", "is also downregulated in", "also downregulated in rett", "downregulated in rett neurons", "rett neurons which", "neurons which is", "which is associated with", "associated with a reduced", "with a reduced capacity", "a reduced capacity of", "reduced capacity of the", "capacity of the mitochondrial", "of the mitochondrial electron", "the mitochondrial electron transport", "mitochondrial electron transport chain", "transport chain ricciardi", "chain ricciardi et", "ricciardi et al. 2011", "al. 2011 li", "2011 li et", "li et al. 2013", "al. 2013 . treatment", "2013 . treatment of", ". treatment of mecp2", "treatment of mecp2 null", "of mecp2 null mice", "mecp2 null mice with", "null mice with igf1", "with igf1 insulin", "igf1 insulin like", "insulin like growth factor", "like growth factor 1", "factor 1 reverses", "1 reverses or", "reverses or ameliorates some", "or ameliorates some rett", "ameliorates some rett like", "some rett like features", "rett like features such", "like features such as", "features such as locomotion", "as locomotion respiratory", "locomotion respiratory difficulties", "respiratory difficulties and irregular", "difficulties and irregular heart", "and irregular heart rate", "heart rate tropea", "rate tropea et", "tropea et al. 2009", "et al. 2009 .

mecp2", "al. 2009 .

mecp2 regulates", "2009 .

mecp2 regulates expression", ".

mecp2 regulates expression of", "regulates expression of a", "expression of a number", "of a number of", "a number of ligands", "number of ligands and", "of ligands and receptors", "ligands and receptors involved", "and receptors involved in", "receptors involved in neuronal", "involved in neuronal development", "in neuronal development and", "neuronal development and function.", "development and function. ligands", "and function. ligands regulated", "function. ligands regulated by", "ligands regulated by mecp2", "regulated by mecp2 include", "by mecp2 include bdnf", "include bdnf reviewed", "bdnf reviewed by", "reviewed by li and", "by li and pozzo", "li and pozzo miller", "and pozzo miller 2014", "miller 2014 and", "2014 and khorshidahmad", "and khorshidahmad et al.", "khorshidahmad et al. 2016", "2016 crh", "crh mcgill et", "mcgill et al. 2006", "al. 2006 samaco", "2006 samaco et", "samaco et al. 2012", "2012 sst", "somatostatin chahrour", "and dll1 li", "dll1 li et", "li et al. 2014", "al. 2014 . mecp2", "2014 . mecp2 also", ". mecp2 also regulates", "mecp2 also regulates transcription", "also regulates transcription of", "regulates transcription of genes", "transcription of genes involved", "of genes involved in", "genes involved in the", "involved in the synthesis", "in the synthesis of", "the synthesis of the", "synthesis of the neurotransmitter", "of the neurotransmitter gaba", "the neurotransmitter gaba \u2013", "neurotransmitter gaba \u2013 gad1", "\u2013 gad1 chao", "gad1 chao et", "chao et al. 2010", "al. 2010 and", "2010 and gad2", "and gad2 chao", "gad2 chao et", "al. 2010 he", "2010 he et", "he et al. 2014", "2014 . mecp2 may", ". mecp2 may be", "mecp2 may be involved", "may be involved in", "be involved in direct", "involved in direct stimulation", "in direct stimulation of", "direct stimulation of transcription", "stimulation of transcription from", "of transcription from the", "transcription from the glud1", "from the glud1 gene", "the glud1 gene promoter", "gene promoter encoding", "promoter encoding mitochondrial", "encoding mitochondrial glutamate dehydrogenase", "mitochondrial glutamate dehydrogenase 1", "dehydrogenase 1 which", "1 which may", "which may be involved", "be involved in the", "involved in the turnover", "in the turnover of", "the turnover of the", "turnover of the neurotransmitter", "of the neurotransmitter glutamate", "neurotransmitter glutamate livide", "glutamate livide et", "livide et al. 2015", "al. 2015 . receptors", "2015 . receptors regulated", ". receptors regulated by", "receptors regulated by mecp2", "by mecp2 include glutamate", "mecp2 include glutamate receptor", "include glutamate receptor gria2", "receptor gria2 qiu", "gria2 qiu et", "qiu et al. 2012", "2012 nmda", "nmda receptor subunits grin2a", "subunits grin2a durand", "grin2a durand et", "durand et al. 2012", "al. 2012 and", "2012 and grin2b", "and grin2b lee", "grin2b lee et", "lee et al. 2008", "2008 opioid", "receptors oprk1 chahrour", "oprk1 chahrour et", "al. 2008 and", "2008 and oprm1", "and oprm1 hwang", "oprm1 hwang et", "hwang et al. 2009", "al. 2009 hwang", "2009 hwang et", "hwang et al. 2010", "al. 2010 samaco", "2010 samaco et", "2012 gprin1", "gprin1 chahrour et", "2008 met", "met plummer et", "plummer et al. 2013", "2013 notch1", "notch1 li et", "al. 2014 . channels/transporters", "2014 . channels/transporters regulated", ". channels/transporters regulated by", "channels/transporters regulated by mecp2", "by mecp2 include trpc3", "include trpc3 li", "trpc3 li et", "li et al. 2012", "2012 and slc2a3", "and slc2a3 chen", "slc2a3 chen et", "2013 . mecp2 regulates", ". mecp2 regulates transcription", "mecp2 regulates transcription of", "regulates transcription of fkbp5", "of fkbp5 involved", "fkbp5 involved in", "involved in trafficking of", "in trafficking of glucocorticoid", "trafficking of glucocorticoid receptors", "glucocorticoid receptors nuber", "receptors nuber et", "nuber et al. 2005", "al. 2005 urdinguio", "2005 urdinguio et", "urdinguio et al. 2008", "et al. 2008 .", "al. 2008 . mecp2", "2008 . mecp2 is", ". mecp2 is implicated", "mecp2 is implicated in", "is implicated in regulation", "implicated in regulation of", "in regulation of expression", "regulation of expression of", "of expression of sema3f", "of sema3f semaphorin", "sema3f semaphorin 3f", "semaphorin 3f in", "3f in mouse", "in mouse olfactory neurons", "olfactory neurons degano", "neurons degano et", "degano et al. 2009", "et al. 2009 .", "al. 2009 . in", "2009 . in zebrafish", "in zebrafish mecp2", "zebrafish mecp2 is", "is implicated in sensory", "implicated in sensory axon", "in sensory axon guidance", "sensory axon guidance by", "axon guidance by direct", "guidance by direct stimulation", "by direct stimulation of", "stimulation of transcription of", "of transcription of sema5b", "transcription of sema5b and", "of sema5b and robo2", "and robo2 leong", "robo2 leong et", "leong et al. 2015", "al. 2015 . mecp2", "2015 . mecp2 may", ". mecp2 may indirectly", "mecp2 may indirectly regulate", "may indirectly regulate signaling", "indirectly regulate signaling by", "regulate signaling by neuronal", "signaling by neuronal receptor", "by neuronal receptor tyrosine", "neuronal receptor tyrosine kinases", "receptor tyrosine kinases by", "tyrosine kinases by regulating", "kinases by regulating transcription", "by regulating transcription of", "regulating transcription of protein", "transcription of protein tyrosine", "of protein tyrosine phosphatases", "tyrosine phosphatases ptpn1", "ptpn1 krishnan et", "krishnan et al. 2015", "al. 2015 and", "2015 and ptpn4", "and ptpn4 williamson", "ptpn4 williamson et", "williamson et al. 2015", "et al. 2015 .

mecp2", "al. 2015 .

mecp2 regulates", "2015 .

mecp2 regulates transcription", ".

mecp2 regulates transcription of", "regulates transcription of several", "transcription of several transcription", "of several transcription factors", "several transcription factors involved", "transcription factors involved in", "factors involved in functioning", "involved in functioning of", "in functioning of the", "functioning of the nervous", "of the nervous system", "nervous system such", "system such as", "as creb1 mef2c", "rbfox1 chahrour et", "2008 and pparg", "and pparg mann", "pparg mann et", "mann et al. 2010", "al. 2010 joss", "2010 joss moore", "joss moore et al.", "moore et al. 2011", "et al. 2011 .

mecp2", "al. 2011 .

mecp2 associates", "2011 .

mecp2 associates with", ".

mecp2 associates with transcription", "associates with transcription and", "with transcription and chromatin", "transcription and chromatin remodeling", "and chromatin remodeling factors", "remodeling factors such", "factors such as", "as creb1 chahrour", "creb1 chahrour et", "2013 the", "the hdac1/2 containing sin3a", "hdac1/2 containing sin3a co", "containing sin3a co repressor", "sin3a co repressor complex", "repressor complex nan", "complex nan et", "nan et al. 1998", "1998 and", "and the ncor/smrt complex", "ncor/smrt complex lyst", "complex lyst et", "lyst et al. 2013", "al. 2013 ebert", "2013 ebert et", "ebert et al. 2013", "al. 2013 . there", "2013 . there are", ". there are contradictory", "there are contradictory reports", "are contradictory reports on", "contradictory reports on the", "reports on the interaction", "on the interaction of", "the interaction of mecp2", "interaction of mecp2 with", "of mecp2 with the", "mecp2 with the swi/snf", "with the swi/snf chromatin", "the swi/snf chromatin remodeling", "swi/snf chromatin remodeling complex", "remodeling complex harikrishnan", "complex harikrishnan et", "harikrishnan et al. 2005", "al. 2005 hu", "2005 hu et", "hu et al. 2006", "et al. 2006 .", "al. 2006 . interaction", "2006 . interaction of", ". interaction of mecp2", "mecp2 with the dna", "with the dna methyltransferase", "the dna methyltransferase dnmt1", "dna methyltransferase dnmt1 has", "methyltransferase dnmt1 has been", "dnmt1 has been reported", "been reported with", "reported with a", "with a concomitant increase", "a concomitant increase in", "concomitant increase in enzymatic", "increase in enzymatic activity", "in enzymatic activity of", "enzymatic activity of dnmt1", "of dnmt1 kimura", "dnmt1 kimura and", "kimura and shiota 2003", "and shiota 2003 .

in", "shiota 2003 .

in addition", "2003 .

in addition to", ".

in addition to dna", "addition to dna binding", "to dna binding dependent", "dna binding dependent regulation", "binding dependent regulation of", "dependent regulation of gene", "regulation of gene expression", "of gene expression by", "gene expression by mecp2", "by mecp2 mecp2", "mecp2 mecp2 may", "mecp2 may influence gene", "may influence gene expression", "influence gene expression by", "gene expression by interaction", "expression by interaction with", "by interaction with components", "interaction with components of", "with components of the", "components of the drosha", "of the drosha microprocessor", "the drosha microprocessor complex", "drosha microprocessor complex and", "microprocessor complex and the", "complex and the consequent", "and the consequent change", "the consequent change in", "consequent change in the", "change in the levels", "in the levels of", "the levels of mature", "levels of mature micrornas", "mature micrornas cheng", "micrornas cheng et", "cheng et al. 2014", "al. 2014 tsujimura", "2014 tsujimura et", "tsujimura et al. 2015", "et al. 2015 .

increased", "al. 2015 .

increased mecp2", "2015 .

increased mecp2 promoter", ".

increased mecp2 promoter methylation", "mecp2 promoter methylation is", "promoter methylation is observed", "methylation is observed in", "is observed in both", "observed in both male", "in both male and", "both male and female", "male and female autism", "and female autism patients", "autism patients nagarajan", "patients nagarajan et", "nagarajan et al. 2008", "al. 2008 . regulatory", "2008 . regulatory elements", ". regulatory elements that", "regulatory elements that undergo", "elements that undergo methylation", "that undergo methylation are", "undergo methylation are found", "methylation are found in", "are found in the", "found in the promoter", "in the promoter and", "the promoter and the", "promoter and the first", "and the first intron", "the first intron of", "first intron of mecp2", "intron of mecp2 and", "of mecp2 and their", "mecp2 and their methylation", "and their methylation was", "their methylation was shown", "methylation was shown to", "was shown to regulate", "shown to regulate mecp2", "to regulate mecp2 expression", "regulate mecp2 expression in", "mecp2 expression in mice", "in mice liyanage", "mice liyanage et", "liyanage et al. 2013", "al. 2013 . mouse", "2013 . mouse mecp2", ". mouse mecp2 promoter", "mouse mecp2 promoter methylation", "mecp2 promoter methylation was", "promoter methylation was shown", "was shown to be", "shown to be affected", "to be affected by", "be affected by stress", "by stress franklin", "stress franklin et", "franklin et al. 2010", "et al. 2010 .

the", "al. 2010 .

the rett", "2010 .

the rett like", ".

the rett like phenotype", "rett like phenotype of", "like phenotype of mecp2", "phenotype of mecp2 null", "mecp2 null mice is", "null mice is reversible", "is reversible guy", "reversible guy et", "guy et al. 2007", "2007 but", "but appropriate levels of", "appropriate levels of mecp2", "levels of mecp2 expression", "of mecp2 expression need", "mecp2 expression need to", "expression need to be", "need to be achieved", "be achieved alvarez", "achieved alvarez saavedra", "alvarez saavedra et al.", "saavedra et al. 2007", "et al. 2007 .", "al. 2007 . when", "2007 . when mecp2", ". when mecp2 expression", "when mecp2 expression is", "mecp2 expression is restored", "expression is restored in", "is restored in astrocytes", "restored in astrocytes of", "in astrocytes of mecp2", "astrocytes of mecp2 null", "null mice amelioration", "mice amelioration of", "amelioration of rett symptoms", "of rett symptoms occurs", "symptoms occurs involving", "occurs involving non", "involving non cell autonomous", "non cell autonomous positive", "cell autonomous positive effect", "autonomous positive effect on", "positive effect on mutant", "effect on mutant neurons", "on mutant neurons and", "mutant neurons and increasing", "neurons and increasing level", "and increasing level of", "increasing level of the", "level of the excitatory", "of the excitatory glutamate", "the excitatory glutamate transporter", "excitatory glutamate transporter vglut1", "transporter vglut1 lioy", "vglut1 lioy et", "lioy et al. 2011", "et al. 2011 .", "al. 2011 . microglia", "2011 . microglia derived", ". microglia derived from", "microglia derived from mecp2", "derived from mecp2 null", "from mecp2 null mice", "mecp2 null mice releases", "null mice releases higher", "mice releases higher than", "releases higher than normal", "higher than normal levels", "than normal levels of", "normal levels of glutamate", "of glutamate which", "glutamate which has", "which has toxic effect", "has toxic effect on", "toxic effect on neurons.", "effect on neurons. increased", "on neurons. increased glutamate", "neurons. increased glutamate secretion", "increased glutamate secretion may", "glutamate secretion may be", "secretion may be due", "may be due to", "be due to increased", "due to increased levels", "to increased levels of", "increased levels of glutaminase", "of glutaminase gls", "gls involved", "involved in glutamate synthesis", "glutamate synthesis and", "synthesis and increased", "and increased levels of", "increased levels of connexin", "levels of connexin 32", "connexin 32 gjb1", "gjb1 involved", "involved in glutamate release", "glutamate release in", "release in mecp2", "in mecp2 null microglia", "null microglia maezawa", "microglia maezawa and", "maezawa and jin 2010", "and jin 2010 .", "jin 2010 . targeted", "2010 . targeted deletion", ". targeted deletion of", "targeted deletion of mecp2", "deletion of mecp2 from", "of mecp2 from sim1", "mecp2 from sim1 expressing", "from sim1 expressing neurons", "sim1 expressing neurons of", "expressing neurons of the", "neurons of the mouse", "of the mouse hypothalamus", "the mouse hypothalamus recapitulates", "mouse hypothalamus recapitulates some", "hypothalamus recapitulates some rett", "recapitulates some rett syndrome", "some rett syndrome like", "rett syndrome like features", "syndrome like features and", "like features and highlights", "features and highlights the", "and highlights the role", "highlights the role of", "the role of mecp2", "role of mecp2 in", "of mecp2 in feeding", "mecp2 in feeding behavior", "in feeding behavior and", "feeding behavior and response", "behavior and response to", "and response to stress", "to stress fyffe", "stress fyffe et", "fyffe et al. 2008", "et al. 2008 .

mecp2", "al. 2008 .

mecp2 overexpression", ".

mecp2 overexpression similar", "overexpression similar to", "similar to mecp2 duplication", "to mecp2 duplication syndrome", "duplication syndrome causes", "syndrome causes neurologic", "causes neurologic phenotype similar", "neurologic phenotype similar to", "phenotype similar to rett", "to rett collins", "rett collins et", "collins et al. 2004", "al. 2004 luikenhuis", "2004 luikenhuis et", "luikenhuis et al. 2004", "al. 2004 van", "2004 van esch", "van esch et al.", "esch et al. 2005", "al. 2005 alvarez", "2005 alvarez saavedra", "saavedra 2007 van", "2007 van esch", "esch et al. 2012", "al. 2012 . the", "2012 . the phenotype", ". the phenotype of", "the phenotype of the", "phenotype of the mouse", "of the mouse model", "the mouse model of", "mouse model of the", "model of the mecp2", "of the mecp2 duplication", "the mecp2 duplication syndrome", "mecp2 duplication syndrome in", "duplication syndrome in adult", "syndrome in adult mice", "in adult mice is", "adult mice is reversible", "mice is reversible when", "is reversible when mecp2", "reversible when mecp2 expression", "when mecp2 expression levels", "mecp2 expression levels are", "expression levels are corrected", "are corrected sztainberg", "corrected sztainberg et", "sztainberg et al. 2015", "mecp2 is an x chromosome", "is an x chromosome gene", "an x chromosome gene whose", "x chromosome gene whose loss", "chromosome gene whose loss of", "gene whose loss of function", "whose loss of function mutations", "loss of function mutations are", "of function mutations are an", "function mutations are an underlying", "mutations are an underlying cause", "are an underlying cause of", "an underlying cause of the", "underlying cause of the majority", "cause of the majority of", "of the majority of rett", "the majority of rett syndrome", "majority of rett syndrome cases.", "of rett syndrome cases. the", "rett syndrome cases. the mecp2", "syndrome cases. the mecp2 gene", "cases. the mecp2 gene locus", "the mecp2 gene locus consists", "mecp2 gene locus consists of", "gene locus consists of four", "locus consists of four exons.", "consists of four exons. both", "of four exons. both exon", "four exons. both exon 1", "exons. both exon 1 and", "both exon 1 and exon", "exon 1 and exon 2", "1 and exon 2 contain", "and exon 2 contain translation", "exon 2 contain translation start", "2 contain translation start sites.", "contain translation start sites. alternative", "translation start sites. alternative splicing", "start sites. alternative splicing of", "sites. alternative splicing of the", "alternative splicing of the second", "splicing of the second exon", "of the second exon results", "the second exon results in", "second exon results in expression", "exon results in expression of", "results in expression of two", "in expression of two mecp2", "expression of two mecp2 transcript", "of two mecp2 transcript isoforms", "mecp2 transcript isoforms mecp2_e1", "isoforms mecp2_e1 mecp2b", "mecp2_e1 mecp2b or mecp2alpha", "mecp2b or mecp2alpha and", "or mecp2alpha and mecp2_e2", "and mecp2_e2 mecp2a or", "mecp2_e2 mecp2a or mecp2beta", "mecp2a or mecp2beta . the", "or mecp2beta . the n", "mecp2beta . the n terminus", ". the n terminus of", "the n terminus of the", "n terminus of the mecp2_e1", "terminus of the mecp2_e1 isoform", "the mecp2_e1 isoform in", "mecp2_e1 isoform in which", "isoform in which exon", "in which exon 2 is", "which exon 2 is spliced", "exon 2 is spliced out", "is spliced out is", "spliced out is encoded", "out is encoded by", "is encoded by exon 1.", "encoded by exon 1. the", "by exon 1. the n", "exon 1. the n terminus", "1. the n terminus of", "n terminus of the mecp2_e2", "terminus of the mecp2_e2 isoforms", "the mecp2_e2 isoforms which", "mecp2_e2 isoforms which includes", "isoforms which includes both", "which includes both exon 1", "includes both exon 1 and", "and exon 2 is", "exon 2 is encoded", "2 is encoded by", "is encoded by exon 2", "by exon 2 as", "exon 2 as the", "2 as the exon", "as the exon 2 translation", "the exon 2 translation start", "exon 2 translation start site", "2 translation start site is", "translation start site is used.", "start site is used. exons", "site is used. exons 3", "is used. exons 3 and", "used. exons 3 and 4", "exons 3 and 4 are", "3 and 4 are present", "and 4 are present in", "4 are present in both", "are present in both isoforms.", "present in both isoforms. the", "in both isoforms. the mecp2_e2", "both isoforms. the mecp2_e2 isoform", "isoforms. the mecp2_e2 isoform was", "the mecp2_e2 isoform was cloned", "mecp2_e2 isoform was cloned first", "isoform was cloned first and", "was cloned first and is", "cloned first and is therefore", "first and is therefore more", "and is therefore more extensively", "is therefore more extensively studied.", "therefore more extensively studied. the", "more extensively studied. the mecp2_e1", "extensively studied. the mecp2_e1 isoform", "studied. the mecp2_e1 isoform is", "the mecp2_e1 isoform is more", "mecp2_e1 isoform is more abundant", "isoform is more abundant in", "is more abundant in the", "more abundant in the brain", "in the brain mnatzakanian", "the brain mnatzakanian et", "brain mnatzakanian et al.", "et al. 2004 kriaucionis", "al. 2004 kriaucionis and", "2004 kriaucionis and bird", "and bird 2004 kaddoum", "bird 2004 kaddoum et", "2004 kaddoum et al.", "kaddoum et al. 2013 .", "et al. 2013 . mecp2", "al. 2013 . mecp2 isoforms", "2013 . mecp2 isoforms show", ". mecp2 isoforms show different", "mecp2 isoforms show different expression", "isoforms show different expression patterns", "show different expression patterns during", "different expression patterns during mouse", "expression patterns during mouse brain", "patterns during mouse brain development", "during mouse brain development and", "mouse brain development and in", "brain development and in adult", "development and in adult brain", "and in adult brain regions", "adult brain regions dragich", "brain regions dragich et", "regions dragich et al.", "et al. 2007 olson", "al. 2007 olson et", "2007 olson et al.", "olson et al. 2014 .", "et al. 2014 . while", "al. 2014 . while rett", "2014 . while rett syndrome", ". while rett syndrome mutations", "while rett syndrome mutations mainly", "rett syndrome mutations mainly occur", "syndrome mutations mainly occur in", "mutations mainly occur in exons", "mainly occur in exons 3", "occur in exons 3 and", "in exons 3 and 4", "exons 3 and 4 of", "3 and 4 of mecp2", "4 of mecp2 thereby", "of mecp2 thereby affecting", "mecp2 thereby affecting both", "thereby affecting both mecp2 isoforms", "both mecp2 isoforms mnatzakanian", "mecp2 isoforms mnatzakanian et", "isoforms mnatzakanian et al.", "al. 2004 some", "2004 some mutations", "some mutations occur in exon", "mutations occur in exon 1", "in exon 1 affecting", "exon 1 affecting mecp2_e1", "1 affecting mecp2_e1 only.", "affecting mecp2_e1 only. no mutations", "mecp2_e1 only. no mutations have", "only. no mutations have been", "no mutations have been described", "mutations have been described in", "have been described in exon", "been described in exon 2", "in exon 2 gianakopoulos", "exon 2 gianakopoulos et", "2 gianakopoulos et al.", "gianakopoulos et al. 2012 .", "et al. 2012 . knockout", "al. 2012 . knockout of", "2012 . knockout of mecp2_e1", ". knockout of mecp2_e1 isoform", "knockout of mecp2_e1 isoform in", "of mecp2_e1 isoform in mice", "isoform in mice through", "in mice through a", "mice through a naturally", "through a naturally occurring rett", "a naturally occurring rett syndrome", "naturally occurring rett syndrome point", "occurring rett syndrome point mutation", "rett syndrome point mutation which", "syndrome point mutation which affects", "point mutation which affects the", "mutation which affects the first", "which affects the first translation", "affects the first translation codon", "the first translation codon of", "first translation codon of mecp2_e1", "codon of mecp2_e1 recapitulates", "of mecp2_e1 recapitulates rett", "mecp2_e1 recapitulates rett like", "recapitulates rett like phenotype. knockout", "rett like phenotype. knockout of", "like phenotype. knockout of mecp2_e2", "phenotype. knockout of mecp2_e2 isoform", "knockout of mecp2_e2 isoform in", "of mecp2_e2 isoform in mice", "mecp2_e2 isoform in mice does", "isoform in mice does not", "in mice does not result", "mice does not result in", "does not result in impairment", "not result in impairment of", "result in impairment of neurologic", "in impairment of neurologic functions", "of neurologic functions yasui", "neurologic functions yasui et", "functions yasui et al.", "yasui et al. 2014 .", "et al. 2014 . in", "al. 2014 . in mecp2", "2014 . in mecp2 null", ". in mecp2 null mice", "mecp2 null mice transgenic", "null mice transgenic expression", "mice transgenic expression of", "transgenic expression of either mecp2_e1", "expression of either mecp2_e1 or", "of either mecp2_e1 or mecp2_e2", "either mecp2_e1 or mecp2_e2 prevents", "mecp2_e1 or mecp2_e2 prevents development", "or mecp2_e2 prevents development of", "mecp2_e2 prevents development of rett", "prevents development of rett like", "development of rett like phenotype", "rett like phenotype with", "like phenotype with mecp2_e1", "phenotype with mecp2_e1 rescuing", "with mecp2_e1 rescuing more rett", "mecp2_e1 rescuing more rett like", "rescuing more rett like symptoms", "more rett like symptoms than", "rett like symptoms than mecp2_e2.", "like symptoms than mecp2_e2. this", "symptoms than mecp2_e2. this indicates", "than mecp2_e2. this indicates that", "mecp2_e2. this indicates that both", "this indicates that both splice", "indicates that both splice variants", "that both splice variants can", "both splice variants can fulfill", "splice variants can fulfill basic", "variants can fulfill basic mecp2", "can fulfill basic mecp2 functions", "fulfill basic mecp2 functions in", "basic mecp2 functions in the", "mecp2 functions in the mouse", "functions in the mouse brain", "the mouse brain kerr", "mouse brain kerr et", "brain kerr et al.", "kerr et al. 2012 .", "et al. 2012 . changes", "al. 2012 . changes in", "2012 . changes in gene", ". changes in gene expression", "changes in gene expression upon", "in gene expression upon over", "gene expression upon over expression", "expression upon over expression of", "upon over expression of either", "over expression of either mecp2_e1", "either mecp2_e1 or mecp2_e2 imply", "mecp2_e1 or mecp2_e2 imply overlapping", "or mecp2_e2 imply overlapping as", "mecp2_e2 imply overlapping as well", "imply overlapping as well as", "overlapping as well as distinct", "as well as distinct target", "well as distinct target genes", "distinct target genes orlic", "target genes orlic milacic", "genes orlic milacic et", "orlic milacic et al. 2014", "milacic et al. 2014 .

methyl", "et al. 2014 .

methyl cpg", "al. 2014 .

methyl cpg binding", "2014 .

methyl cpg binding protein", ".

methyl cpg binding protein 2", "cpg binding protein 2 encoded", "binding protein 2 encoded by", "protein 2 encoded by the", "2 encoded by the mecp2", "encoded by the mecp2 gene", "by the mecp2 gene binds", "the mecp2 gene binds to", "mecp2 gene binds to methylated", "gene binds to methylated cpg", "binds to methylated cpg sequences", "to methylated cpg sequences in", "methylated cpg sequences in the", "cpg sequences in the dna.", "sequences in the dna. the", "in the dna. the binding", "the dna. the binding is", "dna. the binding is not", "the binding is not generic", "is not generic however", "generic however but", "however but is affected", "but is affected by the", "is affected by the underlying", "affected by the underlying dna", "by the underlying dna sequence", "underlying dna sequence yoon", "dna sequence yoon et", "sequence yoon et al.", "yoon et al. 2003 .", "et al. 2003 . mecp2", "al. 2003 . mecp2 binds", "2003 . mecp2 binds to", ". mecp2 binds to dna", "mecp2 binds to dna containing", "binds to dna containing 5", "to dna containing 5 methylcytosine", "containing 5 methylcytosine 5mc", "5 methylcytosine 5mc dna", "5mc dna a", "dna a dna", "a dna modification associated with", "dna modification associated with transcriptional", "modification associated with transcriptional repression", "with transcriptional repression mellen", "transcriptional repression mellen et", "repression mellen et al.", "al. 2012 both", "2012 both in", "both in the context of", "in the context of cpg", "the context of cpg islands", "context of cpg islands and", "of cpg islands and outside", "cpg islands and outside of", "islands and outside of cpg", "and outside of cpg islands", "of cpg islands chen", "cpg islands chen et", "islands chen et al.", "chen et al. 2015 .", "et al. 2015 . in", "al. 2015 . in addition", ". in addition mecp2", "in addition mecp2 binds", "addition mecp2 binds to", "to dna containing 5 hydroxymethylcytosine", "containing 5 hydroxymethylcytosine 5hmc", "5 hydroxymethylcytosine 5hmc dna", "5hmc dna a", "modification associated with transcriptional activation", "with transcriptional activation mellen", "transcriptional activation mellen et", "activation mellen et al.", "mellen et al. 2012 .", "et al. 2012 . mecp2", "al. 2012 . mecp2 binds", "2012 . mecp2 binds to", "mecp2 binds to dna as", "binds to dna as a", "to dna as a monomer", "as a monomer occupying", "a monomer occupying about", "monomer occupying about 11", "occupying about 11 bp of", "about 11 bp of the", "11 bp of the dna.", "bp of the dna. binding", "of the dna. binding of", "the dna. binding of one", "dna. binding of one mecp2", "binding of one mecp2 molecule", "of one mecp2 molecule facilitates", "one mecp2 molecule facilitates binding", "mecp2 molecule facilitates binding of", "molecule facilitates binding of the", "facilitates binding of the second", "binding of the second mecp2", "of the second mecp2 molecule", "second mecp2 molecule and", "mecp2 molecule and therefore", "molecule and therefore clustering", "and therefore clustering can occur", "therefore clustering can occur at", "clustering can occur at target", "can occur at target sites.", "occur at target sites. mecp2", "at target sites. mecp2 binding", "target sites. mecp2 binding to", "sites. mecp2 binding to chromatin", "mecp2 binding to chromatin may", "binding to chromatin may be", "to chromatin may be facilitated", "chromatin may be facilitated by", "may be facilitated by nucleosome", "be facilitated by nucleosome methylation", "by nucleosome methylation ghosh", "nucleosome methylation ghosh et", "methylation ghosh et al.", "ghosh et al. 2010 .

mecp2", "et al. 2010 .

mecp2 was", "al. 2010 .

mecp2 was initially", "2010 .

mecp2 was initially proposed", ".

mecp2 was initially proposed to", "was initially proposed to act", "initially proposed to act as", "proposed to act as a", "to act as a generic", "act as a generic repressor", "as a generic repressor of", "a generic repressor of gene", "generic repressor of gene transcription.", "repressor of gene transcription. however", "gene transcription. however high", "transcription. however high throughput", "however high throughput studies", "high throughput studies of mecp2", "throughput studies of mecp2 induced", "studies of mecp2 induced changes", "of mecp2 induced changes in", "mecp2 induced changes in gene", "induced changes in gene expression", "changes in gene expression in", "in gene expression in mouse", "gene expression in mouse hippocampus", "in mouse hippocampus chahrour", "mouse hippocampus chahrour et", "hippocampus chahrour et al.", "2008 and mouse", "and mouse and human cell", "mouse and human cell lines", "human cell lines orlic", "cell lines orlic milacic", "lines orlic milacic et", "et al. 2014 indicate", "al. 2014 indicate that", "2014 indicate that more", "indicate that more genes are", "that more genes are up", "more genes are up regulated", "genes are up regulated than", "are up regulated than down", "up regulated than down regulated", "regulated than down regulated when", "than down regulated when mecp2", "down regulated when mecp2 is", "regulated when mecp2 is overexpressed.", "when mecp2 is overexpressed. at", "mecp2 is overexpressed. at least", "is overexpressed. at least for", "overexpressed. at least for some", "at least for some genes", "least for some genes directly", "for some genes directly upregulated", "some genes directly upregulated by", "genes directly upregulated by mecp2", "upregulated by mecp2 it", "by mecp2 it was", "mecp2 it was shown", "it was shown that a", "was shown that a complex", "shown that a complex of", "that a complex of mecp2", "a complex of mecp2 and", "complex of mecp2 and creb1", "of mecp2 and creb1 was", "mecp2 and creb1 was involved", "and creb1 was involved in", "creb1 was involved in transcriptional", "was involved in transcriptional stimulation", "in transcriptional stimulation chahrour", "transcriptional stimulation chahrour et", "stimulation chahrour et al.", "et al. 2008 chen", "al. 2008 chen et", "2008 chen et al.", "chen et al. 2013 .

mecp2", "et al. 2013 .

mecp2 expression", "al. 2013 .

mecp2 expression is", "2013 .

mecp2 expression is the", ".

mecp2 expression is the highest", "expression is the highest in", "is the highest in postmitotic", "the highest in postmitotic neurons", "highest in postmitotic neurons compared", "in postmitotic neurons compared to", "postmitotic neurons compared to other", "neurons compared to other cell", "compared to other cell types", "other cell types with", "cell types with mecp2", "types with mecp2 being", "with mecp2 being almost as", "mecp2 being almost as abundant", "being almost as abundant as", "almost as abundant as core", "as abundant as core histones.", "abundant as core histones. phosphorylation", "as core histones. phosphorylation of", "core histones. phosphorylation of mecp2", "histones. phosphorylation of mecp2 in", "phosphorylation of mecp2 in response", "of mecp2 in response to", "mecp2 in response to neuronal", "in response to neuronal activity", "response to neuronal activity regulates", "to neuronal activity regulates binding", "neuronal activity regulates binding of", "activity regulates binding of mecp2", "regulates binding of mecp2 to", "binding of mecp2 to dna", "mecp2 to dna suggesting", "to dna suggesting that", "dna suggesting that mecp2", "suggesting that mecp2 may remodel", "that mecp2 may remodel chromatin", "mecp2 may remodel chromatin in", "may remodel chromatin in a", "remodel chromatin in a neuronal", "chromatin in a neuronal activity", "in a neuronal activity dependent", "a neuronal activity dependent manner.", "neuronal activity dependent manner. the", "activity dependent manner. the resulting", "dependent manner. the resulting changes", "manner. the resulting changes in", "the resulting changes in gene", "resulting changes in gene expression", "changes in gene expression would", "in gene expression would then", "gene expression would then modulate", "expression would then modulate synaptic", "would then modulate synaptic plasticity", "then modulate synaptic plasticity and", "modulate synaptic plasticity and behavior", "plasticity and behavior reviewed", "and behavior reviewed by", "behavior reviewed by ebert", "reviewed by ebert and greenberg", "by ebert and greenberg 2013", "ebert and greenberg 2013 .", "and greenberg 2013 . in", "greenberg 2013 . in human", "2013 . in human embryonic", ". in human embryonic stem", "in human embryonic stem cell", "human embryonic stem cell derived", "embryonic stem cell derived rett", "stem cell derived rett syndrome", "cell derived rett syndrome neurons", "rett syndrome neurons loss", "syndrome neurons loss of", "neurons loss of mecp2", "loss of mecp2 is associated", "of mecp2 is associated with", "mecp2 is associated with a", "is associated with a significant", "associated with a significant reduction", "with a significant reduction in", "a significant reduction in transcription", "significant reduction in transcription of", "reduction in transcription of neuronally", "in transcription of neuronally active", "transcription of neuronally active genes", "neuronally active genes as", "active genes as well", "genes as well as", "as well as the reduction", "well as the reduction in", "as the reduction in nascent", "the reduction in nascent protein", "reduction in nascent protein synthesis.", "in nascent protein synthesis. the", "nascent protein synthesis. the reduction", "protein synthesis. the reduction in", "synthesis. the reduction in nascent", "reduction in nascent protein synthesis", "in nascent protein synthesis can", "nascent protein synthesis can at", "protein synthesis can at least", "synthesis can at least in", "can at least in part", "at least in part be", "least in part be attributed", "in part be attributed to", "part be attributed to the", "be attributed to the decreased", "attributed to the decreased activity", "to the decreased activity of", "the decreased activity of the", "decreased activity of the pi3k/akt/mtor", "activity of the pi3k/akt/mtor signaling", "of the pi3k/akt/mtor signaling pathway.", "the pi3k/akt/mtor signaling pathway. neuronal", "pi3k/akt/mtor signaling pathway. neuronal morphology", "pathway. neuronal morphology reduced", "neuronal morphology reduced soma", "morphology reduced soma size", "reduced soma size and", "soma size and the", "size and the level", "and the level of protein", "the level of protein synthesis", "level of protein synthesis in", "of protein synthesis in rett", "protein synthesis in rett neurons", "synthesis in rett neurons can", "in rett neurons can be", "rett neurons can be ameliorated", "neurons can be ameliorated by", "can be ameliorated by treating", "be ameliorated by treating the", "ameliorated by treating the cells", "by treating the cells with", "treating the cells with growth", "the cells with growth factors", "cells with growth factors which", "with growth factors which activate", "growth factors which activate the", "factors which activate the pi3k/akt/mtor", "which activate the pi3k/akt/mtor cascade", "activate the pi3k/akt/mtor cascade or", "the pi3k/akt/mtor cascade or by", "pi3k/akt/mtor cascade or by inhibition", "cascade or by inhibition of", "or by inhibition of pten", "inhibition of pten the", "of pten the negative", "pten the negative regulator", "the negative regulator of akt", "negative regulator of akt activation.", "regulator of akt activation. mitochondrial", "of akt activation. mitochondrial gene", "akt activation. mitochondrial gene expression", "activation. mitochondrial gene expression is", "mitochondrial gene expression is also", "gene expression is also downregulated", "expression is also downregulated in", "is also downregulated in rett", "also downregulated in rett neurons", "in rett neurons which", "rett neurons which is", "neurons which is associated", "which is associated with a", "is associated with a reduced", "associated with a reduced capacity", "with a reduced capacity of", "a reduced capacity of the", "reduced capacity of the mitochondrial", "capacity of the mitochondrial electron", "of the mitochondrial electron transport", "the mitochondrial electron transport chain", "electron transport chain ricciardi", "transport chain ricciardi et", "chain ricciardi et al.", "et al. 2011 li", "al. 2011 li et", "2011 li et al.", "li et al. 2013 .", "et al. 2013 . treatment", "al. 2013 . treatment of", "2013 . treatment of mecp2", ". treatment of mecp2 null", "treatment of mecp2 null mice", "of mecp2 null mice with", "mecp2 null mice with igf1", "mice with igf1 insulin", "with igf1 insulin like", "igf1 insulin like growth", "insulin like growth factor 1", "growth factor 1 reverses", "factor 1 reverses or", "1 reverses or ameliorates", "reverses or ameliorates some rett", "or ameliorates some rett like", "ameliorates some rett like features", "some rett like features such", "rett like features such as", "like features such as locomotion", "such as locomotion respiratory", "as locomotion respiratory difficulties", "locomotion respiratory difficulties and", "respiratory difficulties and irregular heart", "difficulties and irregular heart rate", "irregular heart rate tropea", "heart rate tropea et", "rate tropea et al.", "tropea et al. 2009 .

mecp2", "et al. 2009 .

mecp2 regulates", "al. 2009 .

mecp2 regulates expression", "2009 .

mecp2 regulates expression of", ".

mecp2 regulates expression of a", "regulates expression of a number", "expression of a number of", "of a number of ligands", "a number of ligands and", "number of ligands and receptors", "of ligands and receptors involved", "ligands and receptors involved in", "and receptors involved in neuronal", "receptors involved in neuronal development", "involved in neuronal development and", "in neuronal development and function.", "neuronal development and function. ligands", "development and function. ligands regulated", "and function. ligands regulated by", "function. ligands regulated by mecp2", "ligands regulated by mecp2 include", "regulated by mecp2 include bdnf", "mecp2 include bdnf reviewed", "include bdnf reviewed by", "bdnf reviewed by li", "reviewed by li and pozzo", "by li and pozzo miller", "li and pozzo miller 2014", "pozzo miller 2014 and", "miller 2014 and khorshidahmad", "2014 and khorshidahmad et", "and khorshidahmad et al. 2016", "al. 2016 crh", "crh mcgill et al.", "et al. 2006 samaco", "al. 2006 samaco et", "2006 samaco et al.", "al. 2012 sst", "somatostatin chahrour et", "2008 and dll1", "and dll1 li et", "dll1 li et al.", "li et al. 2014 .", "et al. 2014 . mecp2", "al. 2014 . mecp2 also", "2014 . mecp2 also regulates", ". mecp2 also regulates transcription", "mecp2 also regulates transcription of", "also regulates transcription of genes", "regulates transcription of genes involved", "transcription of genes involved in", "of genes involved in the", "genes involved in the synthesis", "involved in the synthesis of", "in the synthesis of the", "the synthesis of the neurotransmitter", "synthesis of the neurotransmitter gaba", "of the neurotransmitter gaba \u2013", "the neurotransmitter gaba \u2013 gad1", "gaba \u2013 gad1 chao", "\u2013 gad1 chao et", "gad1 chao et al.", "et al. 2010 and", "al. 2010 and gad2", "and gad2 chao et", "gad2 chao et al.", "et al. 2010 he", "al. 2010 he et", "2010 he et al.", "he et al. 2014 .", "al. 2014 . mecp2 may", "2014 . mecp2 may be", ". mecp2 may be involved", "mecp2 may be involved in", "may be involved in direct", "be involved in direct stimulation", "involved in direct stimulation of", "in direct stimulation of transcription", "direct stimulation of transcription from", "stimulation of transcription from the", "of transcription from the glud1", "transcription from the glud1 gene", "from the glud1 gene promoter", "glud1 gene promoter encoding", "gene promoter encoding mitochondrial", "promoter encoding mitochondrial glutamate", "encoding mitochondrial glutamate dehydrogenase 1", "glutamate dehydrogenase 1 which", "dehydrogenase 1 which may", "1 which may be", "which may be involved in", "may be involved in the", "be involved in the turnover", "involved in the turnover of", "in the turnover of the", "the turnover of the neurotransmitter", "turnover of the neurotransmitter glutamate", "the neurotransmitter glutamate livide", "neurotransmitter glutamate livide et", "glutamate livide et al.", "livide et al. 2015 .", "et al. 2015 . receptors", "al. 2015 . receptors regulated", "2015 . receptors regulated by", ". receptors regulated by mecp2", "receptors regulated by mecp2 include", "regulated by mecp2 include glutamate", "by mecp2 include glutamate receptor", "mecp2 include glutamate receptor gria2", "glutamate receptor gria2 qiu", "receptor gria2 qiu et", "gria2 qiu et al.", "al. 2012 nmda", "2012 nmda receptor", "receptor subunits grin2a durand", "subunits grin2a durand et", "grin2a durand et al.", "et al. 2012 and", "al. 2012 and grin2b", "and grin2b lee et", "grin2b lee et al.", "al. 2008 opioid", "2008 opioid receptors", "opioid receptors oprk1 chahrour", "receptors oprk1 chahrour et", "oprk1 chahrour et al.", "et al. 2008 and", "al. 2008 and oprm1", "and oprm1 hwang et", "oprm1 hwang et al.", "et al. 2009 hwang", "al. 2009 hwang et", "2009 hwang et al.", "et al. 2010 samaco", "al. 2010 samaco et", "2010 samaco et al.", "al. 2012 gprin1", "gprin1 chahrour et al.", "al. 2008 met", "met plummer et al.", "al. 2013 notch1", "notch1 li et al.", "et al. 2014 . channels/transporters", "al. 2014 . channels/transporters regulated", "2014 . channels/transporters regulated by", ". channels/transporters regulated by mecp2", "channels/transporters regulated by mecp2 include", "regulated by mecp2 include trpc3", "mecp2 include trpc3 li", "include trpc3 li et", "trpc3 li et al.", "al. 2012 and slc2a3", "and slc2a3 chen et", "slc2a3 chen et al.", "chen et al. 2013 .", "al. 2013 . mecp2 regulates", "2013 . mecp2 regulates transcription", ". mecp2 regulates transcription of", "mecp2 regulates transcription of fkbp5", "transcription of fkbp5 involved", "of fkbp5 involved in", "fkbp5 involved in trafficking", "involved in trafficking of glucocorticoid", "in trafficking of glucocorticoid receptors", "of glucocorticoid receptors nuber", "glucocorticoid receptors nuber et", "receptors nuber et al.", "et al. 2005 urdinguio", "al. 2005 urdinguio et", "2005 urdinguio et al.", "urdinguio et al. 2008 .", "et al. 2008 . mecp2", "al. 2008 . mecp2 is", "2008 . mecp2 is implicated", ". mecp2 is implicated in", "mecp2 is implicated in regulation", "is implicated in regulation of", "implicated in regulation of expression", "in regulation of expression of", "regulation of expression of sema3f", "expression of sema3f semaphorin", "of sema3f semaphorin 3f", "semaphorin 3f in mouse", "3f in mouse olfactory", "mouse olfactory neurons degano", "olfactory neurons degano et", "neurons degano et al.", "degano et al. 2009 .", "et al. 2009 . in", "al. 2009 . in zebrafish", ". in zebrafish mecp2", "in zebrafish mecp2 is", "zebrafish mecp2 is implicated", "mecp2 is implicated in sensory", "is implicated in sensory axon", "implicated in sensory axon guidance", "in sensory axon guidance by", "sensory axon guidance by direct", "axon guidance by direct stimulation", "guidance by direct stimulation of", "by direct stimulation of transcription", "direct stimulation of transcription of", "stimulation of transcription of sema5b", "of transcription of sema5b and", "transcription of sema5b and robo2", "sema5b and robo2 leong", "and robo2 leong et", "robo2 leong et al.", "leong et al. 2015 .", "et al. 2015 . mecp2", "al. 2015 . mecp2 may", "2015 . mecp2 may indirectly", ". mecp2 may indirectly regulate", "mecp2 may indirectly regulate signaling", "may indirectly regulate signaling by", "indirectly regulate signaling by neuronal", "regulate signaling by neuronal receptor", "signaling by neuronal receptor tyrosine", "by neuronal receptor tyrosine kinases", "neuronal receptor tyrosine kinases by", "receptor tyrosine kinases by regulating", "tyrosine kinases by regulating transcription", "kinases by regulating transcription of", "by regulating transcription of protein", "regulating transcription of protein tyrosine", "transcription of protein tyrosine phosphatases", "protein tyrosine phosphatases ptpn1", "phosphatases ptpn1 krishnan", "ptpn1 krishnan et al.", "et al. 2015 and", "al. 2015 and ptpn4", "and ptpn4 williamson et", "ptpn4 williamson et al.", "williamson et al. 2015 .

mecp2", "et al. 2015 .

mecp2 regulates", "al. 2015 .

mecp2 regulates transcription", "2015 .

mecp2 regulates transcription of", ".

mecp2 regulates transcription of several", "regulates transcription of several transcription", "transcription of several transcription factors", "of several transcription factors involved", "several transcription factors involved in", "transcription factors involved in functioning", "factors involved in functioning of", "involved in functioning of the", "in functioning of the nervous", "functioning of the nervous system", "the nervous system such", "nervous system such as", "system such as creb1", "such as creb1 mef2c", "creb1 mef2c rbfox1", "mef2c rbfox1 chahrour", "rbfox1 chahrour et al.", "al. 2008 and pparg", "and pparg mann et", "pparg mann et al.", "et al. 2010 joss", "al. 2010 joss moore", "2010 joss moore et", "joss moore et al. 2011", "moore et al. 2011 .

mecp2", "et al. 2011 .

mecp2 associates", "al. 2011 .

mecp2 associates with", "2011 .

mecp2 associates with transcription", ".

mecp2 associates with transcription and", "associates with transcription and chromatin", "with transcription and chromatin remodeling", "transcription and chromatin remodeling factors", "chromatin remodeling factors such", "remodeling factors such as", "factors such as creb1", "such as creb1 chahrour", "as creb1 chahrour et", "creb1 chahrour et al.", "al. 2013 the", "2013 the hdac1/2", "the hdac1/2 containing sin3a co", "hdac1/2 containing sin3a co repressor", "containing sin3a co repressor complex", "co repressor complex nan", "repressor complex nan et", "complex nan et al.", "al. 1998 and", "1998 and the", "the ncor/smrt complex lyst", "ncor/smrt complex lyst et", "complex lyst et al.", "et al. 2013 ebert", "al. 2013 ebert et", "2013 ebert et al.", "ebert et al. 2013 .", "et al. 2013 . there", "al. 2013 . there are", "2013 . there are contradictory", ". there are contradictory reports", "there are contradictory reports on", "are contradictory reports on the", "contradictory reports on the interaction", "reports on the interaction of", "on the interaction of mecp2", "the interaction of mecp2 with", "interaction of mecp2 with the", "of mecp2 with the swi/snf", "mecp2 with the swi/snf chromatin", "with the swi/snf chromatin remodeling", "the swi/snf chromatin remodeling complex", "chromatin remodeling complex harikrishnan", "remodeling complex harikrishnan et", "complex harikrishnan et al.", "et al. 2005 hu", "al. 2005 hu et", "2005 hu et al.", "hu et al. 2006 .", "et al. 2006 . interaction", "al. 2006 . interaction of", "2006 . interaction of mecp2", ". interaction of mecp2 with", "of mecp2 with the dna", "mecp2 with the dna methyltransferase", "with the dna methyltransferase dnmt1", "the dna methyltransferase dnmt1 has", "dna methyltransferase dnmt1 has been", "methyltransferase dnmt1 has been reported", "has been reported with", "been reported with a", "reported with a concomitant", "with a concomitant increase in", "a concomitant increase in enzymatic", "concomitant increase in enzymatic activity", "increase in enzymatic activity of", "in enzymatic activity of dnmt1", "activity of dnmt1 kimura", "of dnmt1 kimura and", "dnmt1 kimura and shiota", "kimura and shiota 2003 .

in", "and shiota 2003 .

in addition", "shiota 2003 .

in addition to", "2003 .

in addition to dna", ".

in addition to dna binding", "addition to dna binding dependent", "to dna binding dependent regulation", "dna binding dependent regulation of", "binding dependent regulation of gene", "dependent regulation of gene expression", "regulation of gene expression by", "of gene expression by mecp2", "expression by mecp2 mecp2", "by mecp2 mecp2 may", "mecp2 mecp2 may influence", "mecp2 may influence gene expression", "may influence gene expression by", "influence gene expression by interaction", "gene expression by interaction with", "expression by interaction with components", "by interaction with components of", "interaction with components of the", "with components of the drosha", "components of the drosha microprocessor", "of the drosha microprocessor complex", "the drosha microprocessor complex and", "drosha microprocessor complex and the", "microprocessor complex and the consequent", "complex and the consequent change", "and the consequent change in", "the consequent change in the", "consequent change in the levels", "change in the levels of", "in the levels of mature", "the levels of mature micrornas", "of mature micrornas cheng", "mature micrornas cheng et", "micrornas cheng et al.", "et al. 2014 tsujimura", "al. 2014 tsujimura et", "2014 tsujimura et al.", "tsujimura et al. 2015 .

increased", "et al. 2015 .

increased mecp2", "al. 2015 .

increased mecp2 promoter", "2015 .

increased mecp2 promoter methylation", ".

increased mecp2 promoter methylation is", "mecp2 promoter methylation is observed", "promoter methylation is observed in", "methylation is observed in both", "is observed in both male", "observed in both male and", "in both male and female", "both male and female autism", "male and female autism patients", "female autism patients nagarajan", "autism patients nagarajan et", "patients nagarajan et al.", "nagarajan et al. 2008 .", "et al. 2008 . regulatory", "al. 2008 . regulatory elements", "2008 . regulatory elements that", ". regulatory elements that undergo", "regulatory elements that undergo methylation", "elements that undergo methylation are", "that undergo methylation are found", "undergo methylation are found in", "methylation are found in the", "are found in the promoter", "found in the promoter and", "in the promoter and the", "the promoter and the first", "promoter and the first intron", "and the first intron of", "the first intron of mecp2", "first intron of mecp2 and", "intron of mecp2 and their", "of mecp2 and their methylation", "mecp2 and their methylation was", "and their methylation was shown", "their methylation was shown to", "methylation was shown to regulate", "was shown to regulate mecp2", "shown to regulate mecp2 expression", "to regulate mecp2 expression in", "regulate mecp2 expression in mice", "expression in mice liyanage", "in mice liyanage et", "mice liyanage et al.", "liyanage et al. 2013 .", "et al. 2013 . mouse", "al. 2013 . mouse mecp2", "2013 . mouse mecp2 promoter", ". mouse mecp2 promoter methylation", "mouse mecp2 promoter methylation was", "mecp2 promoter methylation was shown", "promoter methylation was shown to", "methylation was shown to be", "was shown to be affected", "shown to be affected by", "to be affected by stress", "affected by stress franklin", "by stress franklin et", "stress franklin et al.", "franklin et al. 2010 .

the", "et al. 2010 .

the rett", "al. 2010 .

the rett like", "2010 .

the rett like phenotype", ".

the rett like phenotype of", "rett like phenotype of mecp2", "like phenotype of mecp2 null", "phenotype of mecp2 null mice", "of mecp2 null mice is", "mecp2 null mice is reversible", "mice is reversible guy", "is reversible guy et", "reversible guy et al.", "al. 2007 but", "2007 but appropriate", "but appropriate levels of mecp2", "appropriate levels of mecp2 expression", "levels of mecp2 expression need", "of mecp2 expression need to", "mecp2 expression need to be", "expression need to be achieved", "to be achieved alvarez", "be achieved alvarez saavedra", "achieved alvarez saavedra et", "alvarez saavedra et al. 2007", "saavedra et al. 2007 .", "et al. 2007 . when", "al. 2007 . when mecp2", "2007 . when mecp2 expression", ". when mecp2 expression is", "when mecp2 expression is restored", "mecp2 expression is restored in", "expression is restored in astrocytes", "is restored in astrocytes of", "restored in astrocytes of mecp2", "in astrocytes of mecp2 null", "astrocytes of mecp2 null mice", "mecp2 null mice amelioration", "null mice amelioration of", "mice amelioration of rett", "amelioration of rett symptoms occurs", "rett symptoms occurs involving", "symptoms occurs involving non", "occurs involving non cell", "involving non cell autonomous positive", "non cell autonomous positive effect", "cell autonomous positive effect on", "autonomous positive effect on mutant", "positive effect on mutant neurons", "effect on mutant neurons and", "on mutant neurons and increasing", "mutant neurons and increasing level", "neurons and increasing level of", "and increasing level of the", "increasing level of the excitatory", "level of the excitatory glutamate", "of the excitatory glutamate transporter", "the excitatory glutamate transporter vglut1", "glutamate transporter vglut1 lioy", "transporter vglut1 lioy et", "vglut1 lioy et al.", "lioy et al. 2011 .", "et al. 2011 . microglia", "al. 2011 . microglia derived", "2011 . microglia derived from", ". microglia derived from mecp2", "microglia derived from mecp2 null", "derived from mecp2 null mice", "from mecp2 null mice releases", "mecp2 null mice releases higher", "null mice releases higher than", "mice releases higher than normal", "releases higher than normal levels", "higher than normal levels of", "than normal levels of glutamate", "levels of glutamate which", "of glutamate which has", "glutamate which has toxic", "which has toxic effect on", "has toxic effect on neurons.", "toxic effect on neurons. increased", "effect on neurons. increased glutamate", "on neurons. increased glutamate secretion", "neurons. increased glutamate secretion may", "increased glutamate secretion may be", "glutamate secretion may be due", "secretion may be due to", "may be due to increased", "be due to increased levels", "due to increased levels of", "to increased levels of glutaminase", "levels of glutaminase gls", "gls involved in", "in glutamate synthesis and", "glutamate synthesis and increased", "synthesis and increased levels", "and increased levels of connexin", "increased levels of connexin 32", "of connexin 32 gjb1", "gjb1 involved in", "in glutamate release in", "glutamate release in mecp2", "release in mecp2 null", "mecp2 null microglia maezawa", "null microglia maezawa and", "microglia maezawa and jin", "maezawa and jin 2010 .", "and jin 2010 . targeted", "jin 2010 . targeted deletion", "2010 . targeted deletion of", ". targeted deletion of mecp2", "targeted deletion of mecp2 from", "deletion of mecp2 from sim1", "of mecp2 from sim1 expressing", "mecp2 from sim1 expressing neurons", "from sim1 expressing neurons of", "sim1 expressing neurons of the", "expressing neurons of the mouse", "neurons of the mouse hypothalamus", "of the mouse hypothalamus recapitulates", "the mouse hypothalamus recapitulates some", "mouse hypothalamus recapitulates some rett", "hypothalamus recapitulates some rett syndrome", "recapitulates some rett syndrome like", "some rett syndrome like features", "rett syndrome like features and", "syndrome like features and highlights", "like features and highlights the", "features and highlights the role", "and highlights the role of", "highlights the role of mecp2", "the role of mecp2 in", "role of mecp2 in feeding", "of mecp2 in feeding behavior", "mecp2 in feeding behavior and", "in feeding behavior and response", "feeding behavior and response to", "behavior and response to stress", "response to stress fyffe", "to stress fyffe et", "stress fyffe et al.", "fyffe et al. 2008 .

mecp2", "et al. 2008 .

mecp2 overexpression", "2008 .

mecp2 overexpression similar", ".

mecp2 overexpression similar to", "overexpression similar to mecp2", "similar to mecp2 duplication syndrome", "mecp2 duplication syndrome causes", "duplication syndrome causes neurologic", "syndrome causes neurologic phenotype", "causes neurologic phenotype similar to", "neurologic phenotype similar to rett", "similar to rett collins", "to rett collins et", "rett collins et al.", "et al. 2004 luikenhuis", "al. 2004 luikenhuis et", "2004 luikenhuis et al.", "et al. 2004 van", "al. 2004 van esch", "2004 van esch et", "van esch et al. 2005", "et al. 2005 alvarez", "al. 2005 alvarez saavedra", "2005 alvarez saavedra 2007", "alvarez saavedra 2007 van", "saavedra 2007 van esch", "2007 van esch et", "van esch et al. 2012", "esch et al. 2012 .", "et al. 2012 . the", "al. 2012 . the phenotype", "2012 . the phenotype of", ". the phenotype of the", "the phenotype of the mouse", "phenotype of the mouse model", "of the mouse model of", "the mouse model of the", "mouse model of the mecp2", "model of the mecp2 duplication", "of the mecp2 duplication syndrome", "the mecp2 duplication syndrome in", "mecp2 duplication syndrome in adult", "duplication syndrome in adult mice", "syndrome in adult mice is", "in adult mice is reversible", "adult mice is reversible when", "mice is reversible when mecp2", "is reversible when mecp2 expression", "reversible when mecp2 expression levels", "when mecp2 expression levels are", "mecp2 expression levels are corrected", "levels are corrected sztainberg", "are corrected sztainberg et", "corrected sztainberg et al.", "sztainberg et al. 2015 ." ] }, { "record_id": "GLY_000594_1_655", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9009391", "r hsa", "hsa 9009391", "r hsa 9009391" ] }, { "record_id": "GLY_000594_1_655", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "extra nuclear", "nuclear estrogen", "estrogen signaling", "extra nuclear estrogen", "nuclear estrogen signaling", "extra nuclear estrogen signaling", "in addition", "addition to", "to its", "its well", "well characterized", "characterized role", "role in", "in estrogen", "estrogen dependent", "dependent transcription", "beta estradiol", "also known", "known as", "as e2", "also plays", "plays a", "a rapid", "non genomic", "genomic role", "role through", "through interaction", "interaction with", "with receptors", "receptors localized", "localized at", "at the", "the plasma", "plasma membrane", "membrane by", "by virtue", "virtue of", "of dynamic", "dynamic palmitoylation.", "palmitoylation. estrogen", "estrogen receptor", "receptor palmitoylation", "palmitoylation is", "is a", "a prerequisite", "prerequisite for", "for the", "the e2", "e2 dependent", "dependent activation", "activation of", "of extra", "nuclear signaling", "signaling both", "both in", "in vitro", "vitro and", "and in", "in animal", "animal models", "acconcia et", "et al", "marino et", "marino and", "and ascenzi", "2006 .", ". non", "genomic signaling", "signaling through", "through the", "the estrogen", "receptor esr1", "esr1 also", "also depends", "depends on", "on receptor", "receptor arginine", "arginine methylation", "methylation by", "by pmrt1", "pedram et", "le romancer", "romancer et", "reviewed in", "in arnal", ".
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extra nuclear", ".
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recent", "2012
recent data have", "
recent data have demonstrated", "data have demonstrated that", "have demonstrated that the", "demonstrated that the membrane", "that the membrane esr1", "the membrane esr1 can", "membrane esr1 can interact", "esr1 can interact with", "can interact with various", "interact with various endocytic", "with various endocytic proteins", "various endocytic proteins to", "endocytic proteins to traffic", "proteins to traffic and", "to traffic and signal", "traffic and signal within", "and signal within the", "signal within the cytoplasm.", "within the cytoplasm. this", "the cytoplasm. this receptor", "cytoplasm. this receptor intracellular", "this receptor intracellular trafficking", "receptor intracellular trafficking appears", "intracellular trafficking appears to", "trafficking appears to be", "appears to be dependent", "to be dependent on", "be dependent on the", "dependent on the phyical", "on the phyical interaction", "the phyical interaction of", "phyical interaction of esr1", "interaction of esr1 with", "of esr1 with specific", "esr1 with specific trans", "with specific trans membrane", "specific trans membrane receptors", "trans membrane receptors such", "membrane receptors such as", "receptors such as igr", "such as igr 1r", "as igr 1r and", "igr 1r and beta", "1r and beta 1", "and beta 1 integrin", "1 integrin sampayo", "integrin sampayo et", "et al 2018", "in addition to its well", "addition to its well characterized", "to its well characterized role", "its well characterized role in", "well characterized role in estrogen", "characterized role in estrogen dependent", "role in estrogen dependent transcription", "estrogen dependent transcription estrogen", "transcription estrogen beta", "beta estradiol also known", "estradiol also known as", "known as e2 also", "as e2 also plays", "e2 also plays a", "plays a rapid non", "a rapid non genomic", "rapid non genomic role", "non genomic role through interaction", "genomic role through interaction with", "role through interaction with receptors", "through interaction with receptors localized", "interaction with receptors localized at", "with receptors localized at the", "receptors localized at the plasma", "localized at the plasma membrane", "at the plasma membrane by", "the plasma membrane by virtue", "plasma membrane by virtue of", "membrane by virtue of dynamic", "by virtue of dynamic palmitoylation.", "virtue of dynamic palmitoylation. estrogen", "of dynamic palmitoylation. estrogen receptor", "dynamic palmitoylation. estrogen receptor palmitoylation", "palmitoylation. estrogen receptor palmitoylation is", "estrogen receptor palmitoylation is a", "receptor palmitoylation is a prerequisite", "palmitoylation is a prerequisite for", "is a prerequisite for the", "a prerequisite for the e2", "prerequisite for the e2 dependent", "for the e2 dependent activation", "the e2 dependent activation of", "e2 dependent activation of extra", "dependent activation of extra nuclear", "activation of extra nuclear signaling", "of extra nuclear signaling both", "extra nuclear signaling both in", "nuclear signaling both in vitro", "signaling both in vitro and", "both in vitro and in", "in vitro and in animal", "vitro and in animal models", "in animal models acconcia", "animal models acconcia et", "models acconcia et al", "acconcia et al 2004", "al 2004 acconcia", "2004 acconcia et al", "acconcia et al 2005", "al 2005 marino", "2005 marino et al", "marino et al 2006", "al 2006 marino", "2006 marino and ascenzi", "marino and ascenzi 2006", "and ascenzi 2006 .", "ascenzi 2006 . non", "2006 . non genomic signaling", ". non genomic signaling through", "non genomic signaling through the", "genomic signaling through the estrogen", "signaling through the estrogen receptor", "through the estrogen receptor esr1", "the estrogen receptor esr1 also", "estrogen receptor esr1 also depends", "receptor esr1 also depends on", "esr1 also depends on receptor", "also depends on receptor arginine", "depends on receptor arginine methylation", "on receptor arginine methylation by", "receptor arginine methylation by pmrt1", "methylation by pmrt1 pedram", "by pmrt1 pedram et", "pmrt1 pedram et al", "pedram et al 2007", "al 2007 pedram", "2007 pedram et al", "pedram et al 2012", "al 2012 le", "2012 le romancer et", "romancer et al 2008", "al 2008 reviewed", "2008 reviewed in arnal", "reviewed in arnal 2017", "arnal 2017 le", "2017 le romancer et", "romancer et al 2011", "2011 .
e2 evoked", ".
e2 evoked extra nuclear", "
e2 evoked extra nuclear signaling", "evoked extra nuclear signaling is", "extra nuclear signaling is independent", "nuclear signaling is independent of", "signaling is independent of the", "is independent of the transcriptional", "independent of the transcriptional activity", "of the transcriptional activity of", "the transcriptional activity of estrogen", "transcriptional activity of estrogen receptors", "activity of estrogen receptors and", "of estrogen receptors and occurs", "estrogen receptors and occurs within", "receptors and occurs within seconds", "and occurs within seconds to", "occurs within seconds to minutes", "within seconds to minutes following", "seconds to minutes following e2", "to minutes following e2 administration", "minutes following e2 administration to", "following e2 administration to target", "e2 administration to target cells.", "administration to target cells. extra", "to target cells. extra nuclear", "target cells. extra nuclear signaling", "cells. extra nuclear signaling consists", "extra nuclear signaling consists of", "nuclear signaling consists of the", "signaling consists of the activation", "consists of the activation of", "of the activation of a", "the activation of a plethora", "activation of a plethora of", "of a plethora of signaling", "a plethora of signaling pathways", "plethora of signaling pathways including", "of signaling pathways including the", "signaling pathways including the raf/map", "pathways including the raf/map kinase", "including the raf/map kinase cascade", "the raf/map kinase cascade and", "raf/map kinase cascade and the", "kinase cascade and the pi3k/akt", "cascade and the pi3k/akt signaling", "and the pi3k/akt signaling cascade", "the pi3k/akt signaling cascade and", "pi3k/akt signaling cascade and governs", "signaling cascade and governs processes", "cascade and governs processes such", "and governs processes such as", "processes such as apoptosis", "as apoptosis cellular", "apoptosis cellular proliferation and", "proliferation and metastasis reviewed", "and metastasis reviewed in", "metastasis reviewed in hammes", "reviewed in hammes et al", "hammes et al 2007", "al 2007 handa", "2007 handa et al", "handa et al 2012", "al 2012 lange", "2012 lange et al", "lange et al 2007", "al 2007 losel", "2007 losel et al", "losel et al 2003", "al 2003 arnal", "2003 arnal et al", "arnal et al 2017", "al 2017 le", "et al 2011 .", "al 2011 . esr", "2011 . esr mediated signaling", ". esr mediated signaling also", "esr mediated signaling also cross", "mediated signaling also cross talks", "signaling also cross talks with", "also cross talks with receptor", "cross talks with receptor tyrosine", "talks with receptor tyrosine kinase", "receptor tyrosine kinase nf", "kinase nf kappa", "nf kappa beta and", "kappa beta and gpcr signaling", "beta and gpcr signaling pathways", "and gpcr signaling pathways by", "gpcr signaling pathways by modulating", "signaling pathways by modulating the", "pathways by modulating the post", "by modulating the post translational", "modulating the post translational modification", "the post translational modification of", "post translational modification of enzymes", "translational modification of enzymes and", "modification of enzymes and other", "of enzymes and other proteins", "enzymes and other proteins and", "and other proteins and regulating", "other proteins and regulating second", "proteins and regulating second messengers", "regulating second messengers reviewed", "second messengers reviewed in", "messengers reviewed in arnal", "reviewed in arnal et al", "al 2017 schwartz", "2017 schwartz et al", "schwartz et al 2016", "al 2016 boonyaratanakornkit", "2016 boonyaratanakornkit 2011", "boonyaratanakornkit 2011 biswas", "2011 biswas et al", "biswas et al 2005", "et al 2005 .", "al 2005 . in", "2005 . in the nervous", ". in the nervous system", "the nervous system e2", "nervous system e2 affects", "system e2 affects neural", "e2 affects neural functions such", "affects neural functions such as", "neural functions such as cognition", "such as cognition behaviour", "cognition behaviour stress", "behaviour stress responses and", "stress responses and reproduction in", "responses and reproduction in part", "and reproduction in part by", "reproduction in part by inducing", "in part by inducing such", "part by inducing such rapid", "by inducing such rapid extra", "inducing such rapid extra nuclear", "such rapid extra nuclear responses", "extra nuclear responses farach", "nuclear responses farach carson", "responses farach carson and", "carson and davis 2003", "davis 2003 losel", "2003 losel et al", "2003 while in", "in endothelial cells non", "endothelial cells non genomic", "cells non genomic esr", "non genomic esr dependent signaling", "genomic esr dependent signaling also", "esr dependent signaling also regulates", "dependent signaling also regulates vasodilation", "signaling also regulates vasodilation through", "also regulates vasodilation through the", "regulates vasodilation through the enos", "vasodilation through the enos pathway", "the enos pathway reviewed", "enos pathway reviewed in", "pathway reviewed in levin", "reviewed in levin 2011", "in levin 2011 .", "levin 2011 .
extra", "2011 .
extra nuclear signaling", ".
extra nuclear signaling additionally", "
extra nuclear signaling additionally cross", "nuclear signaling additionally cross talks", "signaling additionally cross talks with", "additionally cross talks with nuclear", "cross talks with nuclear estrogen", "talks with nuclear estrogen receptor", "with nuclear estrogen receptor signaling", "nuclear estrogen receptor signaling and", "estrogen receptor signaling and is", "receptor signaling and is required", "signaling and is required to", "and is required to control", "is required to control er", "required to control er protein", "to control er protein stability", "er protein stability la", "protein stability la rosa", "stability la rosa et", "rosa et al 2012", "et al 2012
recent", "al 2012
recent data", "2012
recent data have demonstrated", "
recent data have demonstrated that", "data have demonstrated that the", "have demonstrated that the membrane", "demonstrated that the membrane esr1", "that the membrane esr1 can", "the membrane esr1 can interact", "membrane esr1 can interact with", "esr1 can interact with various", "can interact with various endocytic", "interact with various endocytic proteins", "with various endocytic proteins to", "various endocytic proteins to traffic", "endocytic proteins to traffic and", "proteins to traffic and signal", "to traffic and signal within", "traffic and signal within the", "and signal within the cytoplasm.", "signal within the cytoplasm. this", "within the cytoplasm. this receptor", "the cytoplasm. this receptor intracellular", "cytoplasm. this receptor intracellular trafficking", "this receptor intracellular trafficking appears", "receptor intracellular trafficking appears to", "intracellular trafficking appears to be", "trafficking appears to be dependent", "appears to be dependent on", "to be dependent on the", "be dependent on the phyical", "dependent on the phyical interaction", "on the phyical interaction of", "the phyical interaction of esr1", "phyical interaction of esr1 with", "interaction of esr1 with specific", "of esr1 with specific trans", "esr1 with specific trans membrane", "with specific trans membrane receptors", "specific trans membrane receptors such", "trans membrane receptors such as", "membrane receptors such as igr", "receptors such as igr 1r", "such as igr 1r and", "as igr 1r and beta", "igr 1r and beta 1", "1r and beta 1 integrin", "beta 1 integrin sampayo", "1 integrin sampayo et", "integrin sampayo et al", "sampayo et al 2018" ] }, { "record_id": "GLY_000594_1_656", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "901032", "r hsa", "hsa 901032", "r hsa 901032" ] }, { "record_id": "GLY_000594_1_656", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ 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when the", "glycans when the mannose", "when the mannose on 1a", "the mannose on 1a is", "mannose on 1a is trimmed", "1a is trimmed udp", "is trimmed udp glc:glycoprotein", "trimmed udp glc:glycoprotein glucosyltransferases", "udp glc:glycoprotein glucosyltransferases 1 and", "glc:glycoprotein glucosyltransferases 1 and 2", "1 and 2 uggt1", "and 2 uggt1 and", "2 uggt1 and 2", "uggt1 and 2 are", "and 2 are no", "2 are no longer", "are no longer able to", "no longer able to re", "longer able to re add", "able to re add the", "to re add the glucose", "add the glucose and", "the glucose and therefore", "glucose and therefore the", "and therefore the protein is", "therefore the protein is destined", "the protein is destined for", "protein is destined for erad.", "is destined for erad. glycoproteins", "destined for erad. glycoproteins subject", "for erad. glycoproteins subject to", "erad. glycoproteins subject to endoplasmic", "glycoproteins subject to endoplasmic reticulum", "subject to 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2.", "by uggt1 and 2. for", "uggt1 and 2. for years", "and 2. for years it", "2. for years it has", "for years it has been", "years it has been thought", "it has been thought that", "has been thought that the", "been thought that the removal", "thought that the removal of", "that the removal of the", "the removal of the mannose", "removal of the mannose in", "of the mannose in position", "the mannose in position b", "mannose in position b of", "in position b of the", "position b of the n", "b of the n glycan", "of the n glycan was", "the n glycan was the", "n glycan was the signal", "glycan was the signal to", "was the signal to direct", "the signal to direct proteins", "signal to direct proteins to", "to direct proteins to degradation.", "direct proteins to degradation. however", "to degradation. however this", "degradation. however this mechanism", "however this mechanism has", "this mechanism has been described", "mechanism has been described better", "has been described better by", "been described better by avezov", "described better by avezov et", "better by avezov et al", "avezov et al avezov", "et al avezov et", "al avezov et al.", "et al. 2008 and", "al. 2008 and it", "2008 and it has", "and it has been demonstrated", "it has been demonstrated that", "has been demonstrated that even", "been demonstrated that even glycoproteins", "demonstrated that even glycoproteins with", "that even glycoproteins with man8", "even glycoproteins with man8 or", "glycoproteins with man8 or man7", "with man8 or man7 glycans", "man8 or man7 glycans can", "or man7 glycans can be", "man7 glycans can be re", "glycans can be re glucosylated", "can be re glucosylated and", "be re glucosylated and interact", "re glucosylated and interact again", "glucosylated and interact again with", "and interact again with cnx", "cnx or crt for", "or crt for a", "crt for a review", "for a review on this", "a review on this topic", "on this topic see", "this topic see lederkremer", "topic see lederkremer 2009", "see lederkremer 2009 and maattanen", "lederkremer 2009 and maattanen p", "2009 and maattanen p et", "and maattanen p et al", "p et al 2010", "et al 2010 ." ] }, { "record_id": "GLY_000594_1_657", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9010553", "r hsa", "hsa 9010553", "r hsa 9010553" ] }, { "record_id": "GLY_000594_1_657", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of expression", "expression of", "of slits", "slits and", "and robos", "regulation of expression", "of expression of", "expression of slits", "of slits and", "slits and robos", "regulation of expression of", "of expression of slits", "expression of slits and", "of slits and robos", "regulation of expression of slits", "of expression of slits and", "expression of slits and robos", "of slit", "slit and", "and robo", "robo proteins", "proteins is", "is regulated", "regulated at", "at 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type", "in a cell type dependent", "a cell type dependent transcriptional", "cell type dependent transcriptional regulation", "type dependent transcriptional regulation of", "dependent transcriptional regulation of robo1", "regulation of robo1 robo2", "robo1 robo2 robo3", "robo2 robo3 and slit2", "robo3 and slit2 wilson", "and slit2 wilson et", "slit2 wilson et al.", "et al. 2008 marcos", "al. 2008 marcos mondejar", "2008 marcos mondejar et", "marcos mondejar et al. 2012", "et al. 2012 kim", "al. 2012 kim et", "2012 kim et al.", "kim et al. 2016 .", "et al. 2016 . homeobox", "al. 2016 . homeobox transcription", "2016 . homeobox transcription factor", ". homeobox transcription factor hoxa2", "homeobox transcription factor hoxa2 is", "transcription factor hoxa2 is involved", "factor hoxa2 is involved in", "hoxa2 is involved in transcriptional", "is involved in transcriptional regulation", "involved in transcriptional regulation of", "in transcriptional regulation of robo2", "regulation of robo2 geisen", "of robo2 geisen et", "robo2 geisen et al.", "geisen et al. 2008 .", "et al. 2008 . transcription", "al. 2008 . transcription of", "2008 . transcription of slit1", ". transcription of slit1 during", "transcription of slit1 during optic", "of slit1 during optic tract", "slit1 during optic tract development", "during optic tract development in", "optic tract development in xenopus", "tract development in xenopus is", "development in xenopus is stimulated", "in xenopus is stimulated by", "xenopus is stimulated by fgf", "is stimulated by fgf signaling", "stimulated by fgf signaling and", "by fgf signaling and may", "fgf signaling and may also", "signaling and may also involve", "and may also involve the", "may also involve the transcription", "also involve the transcription factor", "involve the transcription factor hoxa2", "transcription factor hoxa2 but", "factor hoxa2 but the", "hoxa2 but the mechanism", "but the mechanism has not", "the mechanism has not been", "mechanism has not been established", "not been established atkinson", "been established atkinson leadbeater", "established atkinson leadbeater et", "atkinson leadbeater et al. 2010", "leadbeater et al. 2010 .", "et al. 2010 . pax6", "al. 2010 . pax6 and", "2010 . pax6 and the", ". pax6 and the homeodomain", "pax6 and the homeodomain transcription", "and the homeodomain transcription factor", "the homeodomain transcription factor nkx2.2", "homeodomain transcription factor nkx2.2 are", "transcription factor nkx2.2 are also", "factor nkx2.2 are also implicated", "nkx2.2 are also implicated in", "are also implicated in regulation", "also implicated in regulation of", "implicated in regulation of slit1", "in regulation of slit1 transcription", "of slit1 transcription genethliou", "slit1 transcription genethliou et", "transcription genethliou et al.", "genethliou et al. 2009 .", "et al. 2009 . an", "al. 2009 . an rna", "2009 . an rna binding", ". an rna binding protein", "rna binding protein msi1", "protein msi1 binds", "msi1 binds robo3 mrna", "binds robo3 mrna and promotes", "robo3 mrna and promotes its", "mrna and promotes its translation", "promotes its translation thus", "its translation thus increasing", "translation thus increasing robo3", "thus increasing robo3 protein levels", "robo3 protein levels kuwako", "protein levels kuwako et", "levels kuwako et al.", "kuwako et al. 2010 .", "et al. 2010 . a", "al. 2010 . a poorly", "2010 . a poorly studied", ". a poorly studied e3", "a poorly studied e3 ubiquitin", "poorly studied e3 ubiquitin ligase", "studied e3 ubiquitin ligase zswim8", "e3 ubiquitin ligase zswim8 promotes", "ubiquitin ligase zswim8 promotes degradation", "ligase zswim8 promotes degradation of", "zswim8 promotes degradation of robo3", "degradation of robo3 wang", "of robo3 wang et", "robo3 wang et al.", "wang et al. 2013 .", "et al. 2013 . robo1", "al. 2013 . robo1 is", "2013 . robo1 is protein", ". robo1 is protein half", "robo1 is protein half life", "is protein half life is", "protein half life is increased", "half life is increased via", "life is increased via deubiquitination", "is increased via deubiquitination of", "increased via deubiquitination of robo1", "via deubiquitination of robo1 by", "deubiquitination of robo1 by a", "of robo1 by a ubiquitin", "robo1 by a ubiquitin protease", "by a ubiquitin protease usp33", "ubiquitin protease usp33 yuasa", "protease usp33 yuasa kawada", "usp33 yuasa kawada et", "yuasa kawada et al. 2009", "et al. 2009 huang", "al. 2009 huang et", "2009 huang et al.", "huang et al. 2015 .", "et al. 2015 . interaction", "al. 2015 . interaction of", "2015 . interaction of slit2", ". interaction of slit2 with", "interaction of slit2 with dag1", "slit2 with dag1 dystroglycan", "dag1 dystroglycan is", "dystroglycan is important for", "is important for proper localization", "important for proper localization of", "for proper localization of slit2", "proper localization of slit2 at", "localization of 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signaling", ".

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signaling", "2014 .

signaling by", ".

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signaling", "al. 2014 .

signaling by", "2014 .

signaling by notch4", "by notch4 similar", "notch4 similar to", "similar to other notch", "to other notch family", "other notch family proteins", "family proteins involves", "proteins involves proteolytic", "involves proteolytic cleavage of", "proteolytic cleavage of the", "cleavage of the membrane", "of the membrane bound", "the membrane bound notch4", "membrane bound notch4 receptor", "bound notch4 receptor and", "notch4 receptor and release", "receptor and release of", "and release of the", "release of the notch4", "of the notch4 intracellular", "the notch4 intracellular domain", "notch4 intracellular domain fragment", "domain fragment nicd4", "nicd4 into the", "the cytosol saxena", "cytosol saxena et", "saxena et al. 2001", "al. 2001 das", "2001 das et", "das et al. 2004", "et al. 2004 .", "al. 2004 . nicd4", "2004 . nicd4 traffics", ". nicd4 traffics from", "nicd4 traffics from the", "traffics from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the nucleus", "the nucleus where", "nucleus where it", "where it acts as", "it acts as a", "acts as a transcription", "as a transcription factor", "transcription factor lin", "factor lin et", "lin et al. 2002", "et al. 2002 .", "notch4 is co expressed with", "is co expressed with dll4", "expressed with dll4 delta", "with dll4 delta 4", "delta 4 and jag1", "and jag1 jagged 1", "jagged 1 in the", "1 in the vascular", "the vascular system shutter", "vascular system shutter et", "system shutter et al.", "et al. 2000 uyttendaele", "al. 2000 uyttendaele et", "2000 uyttendaele et al.", "uyttendaele et al. 2000 .", "et al. 2000 . notch4", "al. 2000 . notch4 can", "2000 . notch4 can be", ". notch4 can be activated", "notch4 can be activated by", "can be activated by dll4", "be activated by dll4 and", "activated by dll4 and jag1", "by dll4 and jag1 when", "dll4 and jag1 when hmvecd", "and jag1 when hmvecd cells", "when hmvecd cells human", "hmvecd cells human primary", "cells human primary endothelial", "human primary endothelial cell line", "primary endothelial cell line derived", "endothelial cell line derived from", "cell line derived from neonatal", "line derived from neonatal dermal", "derived from neonatal dermal microvasculature", "neonatal dermal microvasculature or", "dermal microvasculature or huvec", "microvasculature or huvec cells", "or huvec cells human", "huvec cells human umbilical", "cells human umbilical venous", "human umbilical venous endothelial cell", "umbilical venous endothelial cell line", "endothelial cell line expressing", "cell line expressing recombinant", "line expressing recombinant mouse", "expressing recombinant mouse notch4 are", "recombinant mouse notch4 are co", "mouse notch4 are co cultured", "notch4 are co cultured with", "are co cultured with hmvecd", "co cultured with hmvecd or", "cultured with hmvecd or huvec", "with hmvecd or huvec cells", "hmvecd or huvec cells expressing", "or huvec cells expressing recombinant", "huvec cells expressing recombinant human", "cells expressing recombinant human or", "expressing recombinant human or mouse", "recombinant human or mouse dll4", "or mouse dll4 shawber", "mouse dll4 shawber et", "dll4 shawber et al.", "et al. 2003 shawber", "al. 2003 shawber et", "2003 shawber et al.", "et al. 2007 or", "al. 2007 or mouse", "2007 or mouse jag1", "or mouse jag1 shawber", "mouse jag1 shawber et", "jag1 shawber et al.", "shawber et al. 2007 .", "et al. 2007 . activation", "al. 2007 . activation of", "2007 . activation of notch4", ". activation of notch4 by", "activation of notch4 by dll4", "of notch4 by dll4 and", "notch4 by dll4 and jag1", "by dll4 and jag1 could", "dll4 and jag1 could not", "and jag1 could not be", "jag1 could not be reproduced", "could not be reproduced when", "not be reproduced when the", "be reproduced when the mouse", "reproduced when the mouse fibroblast", "when the mouse fibroblast cell", "the mouse fibroblast cell line", "mouse fibroblast cell line nih", "fibroblast cell line nih 3t3", "cell line nih 3t3 or", "line nih 3t3 or human", "nih 3t3 or human embryonic", "3t3 or human embryonic kidney", "or human embryonic kidney cell", "human embryonic kidney cell line", "embryonic kidney cell line hek293", "kidney cell line hek293 was", "cell line hek293 was transduced", "line hek293 was transduced with", "hek293 was transduced with notch4", "transduced with notch4 or", "with notch4 or either", "notch4 or either dll4", "or either dll4 or", "either dll4 or jag1", "dll4 or jag1 expressing", "or jag1 expressing vectors and", "jag1 expressing vectors and used", "expressing vectors and used in", "vectors and used in co", "and used in co culture", "used in co culture experiments", "co culture experiments aste", "culture experiments aste amezaga", "experiments aste amezaga et", "aste amezaga et al. 2010", "et al. 2010 james", "al. 2010 james et", "2010 james et al.", "james et al. 2014 .

signaling", "et al. 2014 .

signaling by", "al. 2014 .

signaling by notch4", ".

signaling by notch4 similar", "by notch4 similar to", "notch4 similar to other", "similar to other notch family", "to other notch family proteins", "notch family proteins involves", "family proteins involves proteolytic", "proteins involves proteolytic cleavage", "involves proteolytic cleavage of the", "proteolytic cleavage of the membrane", "cleavage of the membrane bound", "of the membrane bound notch4", "the membrane bound notch4 receptor", "membrane bound notch4 receptor and", "bound notch4 receptor and release", "notch4 receptor and release of", "receptor and release of the", "and release of the notch4", "release of the notch4 intracellular", "of the notch4 intracellular domain", "the notch4 intracellular domain fragment", "intracellular domain fragment nicd4", "fragment nicd4 into", "nicd4 into the cytosol", "into the cytosol saxena", "the cytosol saxena et", "cytosol saxena et al.", "et al. 2001 das", "al. 2001 das et", "2001 das et al.", "das et al. 2004 .", "et al. 2004 . nicd4", "al. 2004 . nicd4 traffics", "2004 . nicd4 traffics from", ". nicd4 traffics from the", "nicd4 traffics from the cytosol", "traffics from the cytosol to", "from the cytosol to the", "the cytosol to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it acts", "where it acts as a", "it acts as a transcription", "acts as a transcription factor", "a transcription factor lin", "transcription factor lin et", "factor lin et al.", "lin et al. 2002 ." ] }, { "record_id": "GLY_000594_1_660", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013957", "r hsa", "hsa 9013957", "r hsa 9013957" ] }, { "record_id": "GLY_000594_1_660", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tlr3 mediated", "mediated ticam1", "ticam1 dependent", "dependent programmed", "programmed cell", "cell death", "tlr3 mediated ticam1", "mediated ticam1 dependent", "ticam1 dependent programmed", 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caspases. in", "of caspases. in addition", "caspases. in addition to", "in addition to apoptosis", "to apoptosis tlr3/tlr4", "apoptosis tlr3/tlr4 activation", "tlr3/tlr4 activation induces rip3", "activation induces rip3 dependent", "induces rip3 dependent necroptosis.", "rip3 dependent necroptosis. these", "dependent necroptosis. these two", "necroptosis. these two programmed", "these two programmed cell", "two programmed cell death", "programmed cell death pathways", "cell death pathways may", "death pathways may suppress", "pathways may suppress each", "may suppress each other.", "suppress each other. when", "each other. when the", "other. when the caspase", "when the caspase activity", "the caspase activity is", "caspase activity is impaired", "activity is impaired or", "is impaired or inhibited", "or inhibited certain", "inhibited certain cell", "certain cell types switch", "cell types switch the", "types switch the apoptotic", "switch the apoptotic death", "the apoptotic death program", "apoptotic death program to", "death program to necroptosis", "program to necroptosis in", "to necroptosis in response", "necroptosis in response to", "in response to various", "response to various stimuli", "various stimuli tnf", "fas viral infection", "viral infection and other", "infection and other stress", "and other stress stimuli", "stimuli kalai", "al. 2002 weber", "2002 weber a", "weber a et al.", "a et al. 2010", "al. 2010 feoktistova", "2010 feoktistova m", "feoktistova m et al.", "m et al. 2011", "al. 2011 tenev", "2011 tenev et", "tenev et al 2011", "et al 2011 .", "tlr3 and tlr4 trigger trif", "and tlr4 trigger trif ticam1", "trigger trif ticam1 dependent", "trif ticam1 dependent programmed", "dependent programmed cell death in", "programmed cell death in various", "cell death in various human", "death in various human and", "in various human and mouse", "various human and mouse cells", "and mouse cells kalai", "mouse cells kalai m", "cells kalai m et", "kalai m et al. 2002", "et al. 2002 han", "al. 2002 han kj", "2002 han kj et", "han kj et al. 2004", "et al. 2004 kaiser", "al. 2004 kaiser wj", "2004 kaiser wj and", "kaiser wj and offermann mk", "wj and offermann mk 2005", "offermann mk 2005 estornes", "mk 2005 estornes y", "2005 estornes y et", "estornes y et al. 2012", "et al. 2012 he", "al. 2012 he s", "2012 he s et", "he s et al. 2011", "s et al. 2011 .", "et al. 2011 . apoptosis", "al. 2011 . apoptosis is", "2011 . apoptosis is a", ". apoptosis is a prevalent", "apoptosis is a prevalent form", "is a prevalent form of", "a prevalent form of programmed", "prevalent form of programmed cell", "form of programmed cell death", "of programmed cell death and", "programmed cell death and is", "cell death and is mediated", "death and is mediated by", "and is mediated by the", "is mediated by the activation", "mediated by the activation of", "by the activation of a", "the activation of a set", "activation of a set of", "of a set of caspases.", "a 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"GLY_000594_1_661", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013973", "r hsa", "hsa 9013973", "r hsa 9013973" ] }, { "record_id": "GLY_000594_1_661", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ticam1 dependent", "dependent activation", "activation of", "of irf3/irf7", "ticam1 dependent activation", "dependent activation of", "activation of irf3/irf7", "ticam1 dependent activation of", "dependent activation of irf3/irf7", "ticam1 dependent activation of irf3/irf7", "cell stimulation", "stimulation with", "with viral", "viral double", "double stranded", "rna and", "and bacterial", "bacterial lipopolysaccharide", "activate toll", "toll like", "like receptors", "receptors 3", "and tlr4", "triggering the", "the activation", "activation the", "of two", "two ikk", "ikk related", "related serine/threonine", "serine/threonine kinases", "tank binding", "binding kinase", "kinase 1", "and 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irf3", "

irf3 activation", "activation and", "and interferon", "interferon \u03b2", "production by", "by poly", "poly i:c", "a synthetic", "synthetic analog", "analog of", "of dsrna", "are decreased", "decreased in", "in tbk1", "tbk1 deficient", "deficient mouse", "mouse fibroblasts", "whereas normal", "normal activation", "activation was", "was observed", "observed in", "in the", "the ikbke", "ikbke deficient", "deficient fibroblasts.", "fibroblasts. however", "in double", "double deficient", "of irf3", "irf3 is", "is completely", "completely abolished", "suggesting a", "a partially", "partially redundant", "redundant functions", "functions of", "of tbk1", "and ikk\u03b5", "hemmi h", "h et", "et al.", "2004 .", ".

the", "

the poly", "induced phosphorylation", "phosphorylation of", "and irf3", "irf3 was", "was abolished", "abolished in", "in trif", "knockout human", "human keratinocyte", "keratinocyte hacat", "hacat cells", "bakshi s", "s et", "2017 .", ". ticam1", "ticam1 is", "is utilized", "utilized as", "as an", "an adaptor", "adaptor protein", "protein by", "by tlr3", "tlr3 and", "yamamoto m", "m et", "2003 .", ".

tlr3", "

tlr3 recruits", "recruits and", "and activates", "activates pi3", "pi3 kinase", "which activates", "activates the", "the downstream", "downstream kinase", "leading to", "to full", "full phosphorylation", "phosphorylation and", "and activation", "sarkar sn", "sn et", ". when", "when pi3k", "pi3k is", "is not", "not recruited", "recruited to", "to tlr3", "tlr3 or", "or its", "its activity", "activity is", "is blocked", "is only", "only partially", "partially phosphorylated", "phosphorylated and", "and fails", "fails to", "to bind", "bind the", "the promoter", "promoter of", "of the", "the target", "target gene", "cell stimulation with", "stimulation with viral", "with viral double", "viral double stranded", "stranded ds", "ds rna", "rna and bacterial", "and bacterial lipopolysaccharide", "lipopolysaccharide lps", "lps activate", "activate toll like", "toll like receptors", "like receptors 3", "3 tlr3", "tlr4 respectively", "respectively triggering", "triggering the activation", "the activation the", "activation the activation", "the activation of", "activation of two", "of two ikk", "two ikk related", "ikk related serine/threonine", "related serine/threonine kinases", "kinases tank", "tank binding kinase", "binding kinase 1", "1 tbk1", "and i\u03bab kinase", "i\u03bab kinase \u03b5", "\u03b5 ikk\u03b5", "ikk\u03b5 ikbke", "ikbke which", "which directly phosphorylate", "directly phosphorylate interferon", "phosphorylate interferon regulatory", "interferon regulatory factor", "regulatory factor 3", "3 irf3", "irf3 and", "and irf7 promoting", "irf7 promoting their", "promoting their dimerization", "their dimerization and", "dimerization and translocation", "and translocation into", "translocation into the", "into the nucleus.", "the nucleus. although", "nucleus. although both", "although both kinases", "both kinases show", "kinases show structural", "show structural and", "structural and functional", "and functional similarities", "similarities it", "it seems that", "seems that tbk1", "that tbk1 and", "tbk1 and ikbke", "and ikbke differ", "ikbke differ in", "differ in their", "in their regulation", "their regulation of", "regulation of downstream", "of downstream signaling", "downstream signaling events", "signaling events of", "events of tlr3/tlr4.", "of tlr3/tlr4.

irf3", "tlr3/tlr4.

irf3 activation", "

irf3 activation and", "activation and interferon", "and interferon \u03b2", "\u03b2 ifn\u03b2", "ifn\u03b2 production", "production by poly", "by poly i:c", "a synthetic analog", "synthetic analog of", "analog of dsrna", "dsrna are", "are decreased in", "decreased in tbk1", "in tbk1 deficient", "tbk1 deficient mouse", "deficient mouse fibroblasts", "fibroblasts whereas", "whereas normal activation", "normal activation was", "activation was observed", "was observed in", "observed in the", "in the ikbke", "the ikbke deficient", "ikbke deficient fibroblasts.", "deficient fibroblasts. however", "however in", "in double deficient", "double deficient mouse", "fibroblasts the", "activation of irf3", "of irf3 is", "irf3 is completely", "is completely abolished", "abolished suggesting", "suggesting a partially", "a partially redundant", "partially redundant functions", "redundant functions of", "functions of tbk1", "of tbk1 and", "tbk1 and ikk\u03b5", "hemmi h et", "h et al.", "al. 2004", "2004 .

the", ".

the poly", "

the poly i:c", "i:c induced", "induced phosphorylation of", "phosphorylation of tbk1", "tbk1 and irf3", "and irf3 was", "irf3 was abolished", "was abolished in", "abolished in trif", "trif ticam1", "ticam1 knockout", "knockout human keratinocyte", "human keratinocyte hacat", "keratinocyte hacat cells", "cells bakshi", "bakshi s et", "s et al.", "al. 2017", "2017 . ticam1", ". ticam1 is", "ticam1 is utilized", "is utilized as", "utilized as an", "as an adaptor", "an adaptor protein", "adaptor protein by", "protein by tlr3", "by tlr3 and", "tlr3 and tlr4", "tlr4 yamamoto", "yamamoto m et", "m et al.", "al. 2003", "2003 .

tlr3", ".

tlr3 recruits", "

tlr3 recruits and", "recruits and activates", "and activates pi3", "activates pi3 kinase", "kinase pi3k", "which activates the", "activates the downstream", "the downstream kinase", "kinase akt", "akt leading", "leading to full", "to full phosphorylation", "full phosphorylation and", "phosphorylation and activation", "and activation of", "irf3 sarkar", "sarkar sn et", "sn et al.", "2004 . when", ". when pi3k", "when pi3k is", "pi3k is not", "is not recruited", "not recruited to", "recruited to tlr3", "to tlr3 or", "tlr3 or its", "or its activity", "its activity is", "activity is blocked", "blocked irf3", "irf3 is only", "is only partially", "only partially phosphorylated", "partially phosphorylated and", "phosphorylated and fails", "and fails to", "fails to bind", "to bind the", "bind the promoter", "the promoter of", "promoter of the", "of the target", "the target gene", "gene sarkar", "cell stimulation with viral", "stimulation with viral double", "with viral double stranded", "double stranded ds", "ds rna and", "rna and bacterial lipopolysaccharide", "bacterial lipopolysaccharide lps", "lps activate toll", "activate toll like receptors", "toll like receptors 3", "receptors 3 tlr3", "and tlr4 respectively", "respectively triggering the", "triggering the activation the", "the activation the activation", "activation the activation of", "the activation of two", "activation of two ikk", "of two ikk related", "two ikk related serine/threonine", "ikk related serine/threonine kinases", "serine/threonine kinases tank", "kinases tank binding", "tank binding kinase 1", "kinase 1 tbk1", "tbk1 and i\u03bab", "and i\u03bab kinase \u03b5", "kinase \u03b5 ikk\u03b5", "ikbke which directly", "which directly phosphorylate interferon", "directly phosphorylate interferon regulatory", "phosphorylate interferon regulatory factor", "interferon regulatory factor 3", "factor 3 irf3", "irf3 and irf7", "and irf7 promoting their", "irf7 promoting their dimerization", "promoting their dimerization and", "their dimerization and translocation", "dimerization and translocation into", "and translocation into the", "translocation into the nucleus.", "into the nucleus. although", "the nucleus. although both", "nucleus. although both kinases", "although both kinases show", "both kinases show structural", "kinases show structural and", "show structural and functional", "structural and functional similarities", "functional similarities it", "similarities it seems", "it seems that tbk1", "seems that tbk1 and", "that tbk1 and ikbke", "tbk1 and ikbke differ", "and ikbke differ in", "ikbke differ in their", "differ in their regulation", "in their regulation of", "their regulation of downstream", "regulation of downstream signaling", "of downstream signaling events", "downstream signaling events of", "signaling events of tlr3/tlr4.", "events of tlr3/tlr4.

irf3", "of tlr3/tlr4.

irf3 activation", "tlr3/tlr4.

irf3 activation and", "

irf3 activation and interferon", "activation and interferon \u03b2", "interferon \u03b2 ifn\u03b2", "ifn\u03b2 production by", "production by poly i:c", "i:c a", "a synthetic analog of", "synthetic analog of dsrna", "of dsrna are", "dsrna are decreased", "are decreased in tbk1", "decreased in tbk1 deficient", "in tbk1 deficient mouse", "tbk1 deficient mouse fibroblasts", "mouse fibroblasts whereas", "fibroblasts whereas normal", "whereas normal activation was", "normal activation was observed", "activation was observed in", "was observed in the", "observed in the ikbke", "in the ikbke deficient", "the ikbke deficient fibroblasts.", "ikbke deficient fibroblasts. however", "fibroblasts. however in", "however in double", "in double deficient mouse", "double deficient mouse fibroblasts", "mouse fibroblasts the", "fibroblasts the activation", "the activation of irf3", "activation of irf3 is", "of irf3 is completely", "irf3 is completely abolished", "completely abolished suggesting", "abolished suggesting a", "suggesting a partially redundant", "a partially redundant functions", "partially redundant functions of", "redundant functions of tbk1", "functions of tbk1 and", "of tbk1 and ikk\u03b5", "and ikk\u03b5 ikbke", "ikbke hemmi", "hemmi h et al.", "et al. 2004", "al. 2004 .", "2004 .

the poly", ".

the poly i:c", "poly i:c induced", "i:c induced phosphorylation", "induced phosphorylation of tbk1", "phosphorylation of tbk1 and", "of tbk1 and irf3", "tbk1 and irf3 was", "and irf3 was abolished", "irf3 was abolished in", "was abolished in trif", "in trif ticam1", "ticam1 knockout human", "knockout human keratinocyte hacat", "human keratinocyte hacat cells", "hacat cells bakshi", "cells bakshi s", "bakshi s et al.", "et al. 2017", "al. 2017 .", "2017 . ticam1 is", ". ticam1 is utilized", "ticam1 is utilized as", "is utilized as an", "utilized as an adaptor", "as an adaptor protein", "an adaptor protein by", "adaptor protein by tlr3", "protein by tlr3 and", "by tlr3 and tlr4", "and tlr4 yamamoto", "tlr4 yamamoto m", "yamamoto m et al.", "et al. 2003", "al. 2003 .", "2003 .

tlr3 recruits", ".

tlr3 recruits and", "

tlr3 recruits and activates", "recruits and activates pi3", "and activates pi3 kinase", "pi3 kinase pi3k", "pi3k which", "which activates the downstream", "activates the downstream kinase", "downstream kinase akt", "akt leading to", "leading to full phosphorylation", "to full phosphorylation and", "full phosphorylation and activation", "phosphorylation and activation of", "and activation of irf3", "of irf3 sarkar", "irf3 sarkar sn", "sarkar sn et al.", "2004 . when pi3k", ". when pi3k is", "when pi3k is not", "pi3k is not recruited", "is not recruited to", "not recruited to tlr3", "recruited to tlr3 or", "to tlr3 or its", "tlr3 or its activity", "or its activity is", "its activity is blocked", "is blocked irf3", "blocked irf3 is", "irf3 is only partially", "is only partially phosphorylated", "only partially phosphorylated and", "partially phosphorylated and fails", "phosphorylated and fails to", "and fails to bind", "fails to bind the", "to bind the promoter", "bind the promoter of", "the promoter of the", "promoter of the target", "of the target gene", "target gene sarkar", "gene sarkar sn", "cell stimulation with viral double", "stimulation with viral double stranded", "viral double stranded ds", "stranded ds rna", "ds rna and bacterial", "and bacterial lipopolysaccharide lps", "lipopolysaccharide lps activate", "lps activate toll like", "activate toll like receptors 3", "like receptors 3 tlr3", "3 tlr3 and", "tlr4 respectively triggering", "respectively triggering the activation", "triggering the activation the activation", "the activation the activation of", "activation the activation of two", "the activation of two ikk", "activation of two ikk related", "of two ikk related serine/threonine", "two ikk related serine/threonine kinases", "related serine/threonine kinases tank", "serine/threonine kinases tank binding", "kinases tank binding kinase", "binding kinase 1 tbk1", "1 tbk1 and", "tbk1 and i\u03bab kinase", "i\u03bab kinase \u03b5 ikk\u03b5", "\u03b5 ikk\u03b5 ikbke", "ikk\u03b5 ikbke which", "ikbke which directly phosphorylate", "which directly phosphorylate interferon regulatory", "directly phosphorylate interferon regulatory factor", "phosphorylate interferon regulatory factor 3", "regulatory factor 3 irf3", "3 irf3 and", "irf3 and irf7 promoting", "and irf7 promoting their dimerization", "irf7 promoting their dimerization and", "promoting their dimerization and translocation", "their dimerization and translocation into", "dimerization and translocation into the", "and translocation into the nucleus.", "translocation into the nucleus. although", "into the nucleus. although both", "the nucleus. although both kinases", "nucleus. although both kinases show", "although both kinases show structural", "both kinases show structural and", "kinases show structural and functional", "show structural and functional similarities", "and functional similarities it", "functional similarities it seems", "similarities it seems that", "it seems that tbk1 and", "seems that tbk1 and ikbke", "that tbk1 and ikbke differ", "tbk1 and ikbke differ in", "and ikbke differ in their", "ikbke differ in their regulation", "differ in their regulation of", "in their regulation of downstream", "their regulation of downstream signaling", "regulation of downstream signaling events", "of downstream signaling events of", "downstream signaling events of tlr3/tlr4.", "signaling events of tlr3/tlr4.

irf3", "events of tlr3/tlr4.

irf3 activation", "of tlr3/tlr4.

irf3 activation and", "tlr3/tlr4.

irf3 activation and interferon", "

irf3 activation and interferon \u03b2", "and interferon \u03b2 ifn\u03b2", "\u03b2 ifn\u03b2 production", "ifn\u03b2 production by poly", "poly i:c a", "i:c a synthetic", "a synthetic analog of dsrna", "analog of dsrna are", "of dsrna are decreased", "dsrna are decreased in", "are decreased in tbk1 deficient", "decreased in tbk1 deficient mouse", "in tbk1 deficient mouse fibroblasts", "deficient mouse fibroblasts whereas", "mouse fibroblasts whereas normal", "fibroblasts whereas normal activation", "whereas normal activation was observed", "normal activation was observed in", "activation was observed in the", "was observed in the ikbke", "observed in the ikbke deficient", "in the ikbke deficient fibroblasts.", "the ikbke deficient fibroblasts. however", "deficient fibroblasts. however in", "fibroblasts. however in double", "however in double deficient", "in double deficient mouse fibroblasts", "deficient mouse fibroblasts the", "mouse fibroblasts the activation", "fibroblasts the activation of", "the activation of irf3 is", "activation of irf3 is completely", "of irf3 is completely abolished", "is completely abolished suggesting", "completely abolished suggesting a", "abolished suggesting a partially", "suggesting a partially redundant functions", "a partially redundant functions of", "partially redundant functions of tbk1", "redundant functions of tbk1 and", "functions of tbk1 and ikk\u03b5", "tbk1 and ikk\u03b5 ikbke", "ikbke hemmi h", "h et al. 2004", "et al. 2004 .", "al. 2004 .

the", "2004 .

the poly i:c", "

the poly i:c induced", "poly i:c induced phosphorylation", "i:c induced phosphorylation of", "induced phosphorylation of tbk1 and", "phosphorylation of tbk1 and irf3", "of tbk1 and irf3 was", "tbk1 and irf3 was abolished", "and irf3 was abolished in", "irf3 was abolished in trif", "abolished in trif ticam1", "trif ticam1 knockout", "ticam1 knockout human keratinocyte", "knockout human keratinocyte hacat cells", "keratinocyte hacat cells bakshi", "hacat cells bakshi s", "cells bakshi s et", "s et al. 2017", "et al. 2017 .", "al. 2017 . ticam1", "2017 . ticam1 is utilized", ". ticam1 is utilized as", "ticam1 is utilized as an", "is utilized as an adaptor", "utilized as an adaptor protein", "as an adaptor protein by", "an adaptor protein by tlr3", "adaptor protein by tlr3 and", "protein by tlr3 and tlr4", "tlr3 and tlr4 yamamoto", "and tlr4 yamamoto m", "tlr4 yamamoto m et", "m et al. 2003", "et al. 2003 .", "al. 2003 .

tlr3", "2003 .

tlr3 recruits and", ".

tlr3 recruits and activates", "

tlr3 recruits and activates pi3", "recruits and activates pi3 kinase", "activates pi3 kinase pi3k", "pi3k which activates", "which activates the downstream kinase", "the downstream kinase akt", "kinase akt leading", "akt leading to full", "leading to full phosphorylation and", "to full phosphorylation and activation", "full phosphorylation and activation of", "phosphorylation and activation of irf3", "activation of irf3 sarkar", "of irf3 sarkar sn", "irf3 sarkar sn et", "sn et al. 2004", "al. 2004 . when", "2004 . when pi3k is", ". when pi3k is not", "when pi3k is not recruited", "pi3k is not recruited to", "is not recruited to tlr3", "not recruited to tlr3 or", "recruited to tlr3 or its", "to tlr3 or its activity", "tlr3 or its activity is", "or its activity is blocked", "activity is blocked irf3", "is blocked irf3 is", "blocked irf3 is only", "irf3 is only partially phosphorylated", "is only partially phosphorylated and", "only partially phosphorylated and fails", "partially phosphorylated and fails to", "phosphorylated and fails to bind", "and fails to bind the", "fails to bind the promoter", "to bind the promoter of", "bind the promoter of the", "the promoter of the target", "promoter of the target gene", "the target gene sarkar", "target gene sarkar sn", "gene sarkar sn et" ] }, { "record_id": "GLY_000594_1_662", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9014325", "r hsa", "hsa 9014325", "r hsa 9014325" ] }, { "record_id": "GLY_000594_1_662", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ticam1 traf6", "traf6 dependent", "dependent induction", "induction of", "of tak1", "tak1 complex", "ticam1 traf6 dependent", "traf6 dependent induction", "dependent induction of", "induction of tak1", "of tak1 complex", "ticam1 traf6 dependent induction", "traf6 dependent induction of", "dependent induction of tak1", "induction of tak1 complex", "ticam1 traf6 dependent induction of", "traf6 dependent induction of tak1", "dependent induction of tak1 complex", "in human", "together with", "with ubiquitin", "ubiquitin conjugating", "conjugating e2", "e2 type", "type enzymes", "enzymes ubc13", "ubc13 and", "and uev1a", "also known", "known as", "as ube2v1", "traf6 catalyses", "catalyses lys63", "lys63 linked", "linked ubiquitination.", "ubiquitination. it", "it is", "is believed", "believed that", "that auto", "auto polyubiquitination", "and oligomerization", "oligomerization of", "of traf6", "traf6 is", "is followed", "followed by", "by binding", "binding the", "the ubiquitin", "ubiquitin receptors", "receptors of", "of tab2", "tab2 or", "or tab3", "tak1 binding", "binding protein", "protein 2", "2 and", "and 3", "which stimulates", "stimulates phosphorylation", "phosphorylation and", "and activation", "activation of", "of tgf", "tgf beta", "beta activated", "activated kinase", "kinase 1", "1 tak1", "tak1 .

tak1", ".

tak1 phosphorylates", "phosphorylates ikk", "ikk alpha", "alpha and", "and ikk", "ikk beta", "which in", "in turn", "turn phosphorylate", "phosphorylate nf", "nf kb", "kb inhibitors", "and eventually", "eventually results", "results in", "in ikb", "ikb degradation", "degradation and", "and nf", "kb translocation", "translocation to", "to the", "the nucleus.", "nucleus. also", "also tak1", "tak1 mediates", "mediates jnk", "jnk and", "and p38", "p38 map", "map kinases", "kinases activation", "activation by", "by phosphorylating", "phosphorylating mkk4/7", "mkk4/7 and", "and mkk3/6", "mkk3/6 respectivly", "respectivly resulting", "resulting in", "in the", "the activation", "of many", "many transcription", "transcription factors.", "factors.

the", "

the role", "role of", "is somewhat", "somewhat controversial", "controversial and", "and probably", "probably cell", "cell type", "type specific.", "specific. traf6", "traf6 autoubiquitination", "autoubiquitination was", "was found", "found to", "to be", "be dispensable", "dispensable for", "for traf6", "traf6 function", "function to", "to activate", "activate tak1", "tak1 pathway.", "pathway. these", "these findings", "findings are", "are consistent", "consistent with", "with the", "the new", "new mechanism", "mechanism of", "traf6 mediated", "mediated nf", "kb activation", "activation that", "that was", "was suggested", "suggested by", "by xia", "xia et", "et al.", "2009 .", ". traf6", "traf6 generates", "generates unanchored", "unanchored lys63", "linked polyubiquitin", "polyubiquitin chains", "chains that", "that bind", "bind to", "the regulatory", "regulatory subunits", "subunits of", "ikk nemo", "leading to", "of the", "the kinases.

", "kinases.

xia", "demonstrated in", "in vitro", "vitro that", "that unlike", "unlike polyubiquitin", "chains covalently", "covalently attached", "attached to", "to traf6", "traf6 or", "or irak", "tab2 and", "and nemo", "nemo associated", "associated ubiquitin", "ubiquitin chains", "chains were", "were found", "be unanchored", "unanchored and", "and susceptible", "susceptible to", "to n", "n terminal", "terminal ubiquitin", "ubiquitin cleavage.", "cleavage. only", "only k63", "k63 linked", "but not", "not monomeric", "monomeric ubiquitin", "activated tak1", "tak1 in", "in a", "a dose", "dose dependent", "dependent manner.", "manner. optimal", "optimal activation", "the ikk", "ikk complex", "complex was", "was achieved", "achieved using", "using ubiquitin", "ubiquitin polymers", "polymers containing", "containing both", "both k48", "k48 and", "and k63", "k63 linkages.

furthermore", "the authors", "authors proposed", "proposed that", "that the", "the tak1", "tak1 complexes", "complexes might", "might be", "be brougt", "brougt in", "in close", "close proximity", "proximity by", "binding several", "several tab2/3", "tab2/3 to", "to a", "a single", "single polyubiquitin", "polyubiquitin chain", "chain to", "to facilitate", "facilitate tak1", "tak1 kinase", "kinase trans", "trans phosphorylation.", "phosphorylation. alternativly", "the possibility", "possibility that", "that polyub", "polyub binding", "binding promotes", "promotes allosteric", "allosteric activation", "complex should", "be considered", "walsh et", "et al", "al 2008", "2008 .", "human together", "together with ubiquitin", "with ubiquitin conjugating", "ubiquitin conjugating e2", "conjugating e2 type", "e2 type enzymes", "type enzymes ubc13", "enzymes ubc13 and", "ubc13 and uev1a", "uev1a also", "also known as", "known as ube2v1", "traf6 catalyses lys63", "catalyses lys63 linked", "lys63 linked ubiquitination.", "linked ubiquitination. it", "ubiquitination. it is", "it is believed", "is believed that", "believed that auto", "that auto polyubiquitination", "polyubiquitination and", "and oligomerization of", "oligomerization of traf6", "of traf6 is", "traf6 is followed", "is followed by", "followed by binding", "by binding the", "binding the ubiquitin", "the ubiquitin receptors", "ubiquitin receptors of", "receptors of tab2", "of tab2 or", "tab2 or tab3", "tab3 tak1", "tak1 binding protein", "binding protein 2", "protein 2 and", "2 and 3", "which stimulates phosphorylation", "stimulates phosphorylation and", "phosphorylation and activation", "and activation of", "activation of tgf", "of tgf beta", "tgf beta activated", "beta activated kinase", "activated kinase 1", "kinase 1 tak1", "1 tak1 .

tak1", "tak1 .

tak1 phosphorylates", ".

tak1 phosphorylates ikk", "phosphorylates ikk alpha", "ikk alpha and", "alpha and ikk", "and ikk beta", "beta which", "which in turn", "in turn phosphorylate", "turn phosphorylate nf", "phosphorylate nf kb", "nf kb inhibitors", "ikb and", "and eventually results", "eventually results in", "results in ikb", "in ikb degradation", "ikb degradation and", "degradation and nf", "and nf kb", "nf kb translocation", "kb translocation to", "translocation to the", "to the nucleus.", "the nucleus. also", "nucleus. also tak1", "also tak1 mediates", "tak1 mediates jnk", "mediates jnk and", "jnk and p38", "and p38 map", "p38 map kinases", "map kinases activation", "kinases activation by", "activation by phosphorylating", "by phosphorylating mkk4/7", "phosphorylating mkk4/7 and", "mkk4/7 and mkk3/6", "and mkk3/6 respectivly", "mkk3/6 respectivly resulting", "respectivly resulting in", "resulting in the", "in the activation", "the activation of", "activation of many", "of many transcription", "many transcription factors.", "transcription factors.

the", "factors.

the role", "

the role of", "role of traf6", "traf6 is somewhat", "is somewhat controversial", "somewhat controversial and", "controversial and probably", "and probably cell", "probably cell type", "cell type specific.", "type specific. traf6", "specific. traf6 autoubiquitination", "traf6 autoubiquitination was", "autoubiquitination was found", "was found to", "found to be", "to be dispensable", "be dispensable for", "dispensable for traf6", "for traf6 function", "traf6 function to", "function to activate", "to activate tak1", "activate tak1 pathway.", "tak1 pathway. these", "pathway. these findings", "these findings are", "findings are consistent", "are consistent with", "consistent with the", "with the new", "the new mechanism", "new mechanism of", "mechanism of traf6", "of traf6 mediated", "traf6 mediated nf", "mediated nf kb", "nf kb activation", "kb activation that", "activation that was", "that was suggested", "was suggested by", "suggested by xia", "by xia et", "xia et al.", "al. 2009", "2009 . traf6", ". traf6 generates", "traf6 generates unanchored", "generates unanchored lys63", "unanchored lys63 linked", "lys63 linked polyubiquitin", "linked polyubiquitin chains", "polyubiquitin chains that", "chains that bind", "that bind to", "bind to the", "to the regulatory", "the regulatory subunits", "regulatory subunits of", "subunits of tak1", "tak1 tab2", "tab3 and", "and ikk nemo", "leading to the", "to the activation", "activation of the", "of the kinases.

", "the kinases.

xia", "kinases.

xia et", "2009 demonstrated", "demonstrated in vitro", "in vitro that", "vitro that unlike", "that unlike polyubiquitin", "unlike polyubiquitin chains", "polyubiquitin chains covalently", "chains covalently attached", "covalently attached to", "attached to traf6", "to traf6 or", "traf6 or irak", "irak tab2", "tab2 and nemo", "and nemo associated", "nemo associated ubiquitin", "associated ubiquitin chains", "ubiquitin chains were", "chains were found", "were found to", "to be unanchored", "be unanchored and", "unanchored and susceptible", "and susceptible to", "susceptible to n", "to n terminal", "n terminal ubiquitin", "terminal ubiquitin cleavage.", "ubiquitin cleavage. only", "cleavage. only k63", "only k63 linked", "k63 linked polyubiquitin", "chains but", "but not monomeric", "not monomeric ubiquitin", "ubiquitin activated", "activated tak1 in", "tak1 in a", "in a dose", "a dose dependent", "dose dependent manner.", "dependent manner. optimal", "manner. optimal activation", "optimal activation of", "of the ikk", "the ikk complex", "ikk complex was", "complex was achieved", "was achieved using", "achieved using ubiquitin", "using ubiquitin polymers", "ubiquitin polymers containing", "polymers containing both", "containing both k48", "both k48 and", "k48 and k63", "and k63 linkages.

furthermore", "linkages.

furthermore the", "the authors proposed", "authors proposed that", "proposed that the", "that the tak1", "the tak1 complexes", "tak1 complexes might", "complexes might be", "might be brougt", "be brougt in", "brougt in close", "in close proximity", "close proximity by", "proximity by binding", "by binding several", "binding several tab2/3", "several tab2/3 to", "tab2/3 to a", "to a single", "a single polyubiquitin", "single polyubiquitin chain", "polyubiquitin chain to", "chain to facilitate", "to facilitate tak1", "facilitate tak1 kinase", "tak1 kinase trans", "kinase trans phosphorylation.", "trans phosphorylation. alternativly", "alternativly the", "the possibility that", "possibility that polyub", "that polyub binding", "polyub binding promotes", "binding promotes allosteric", "promotes allosteric activation", "allosteric activation of", "activation of tak1", "tak1 complex should", "should be", "considered walsh", "walsh et al", "et al 2008", "al 2008 .", "in human together", "human together with", "together with ubiquitin conjugating", "with ubiquitin conjugating e2", "ubiquitin conjugating e2 type", "conjugating e2 type enzymes", "e2 type enzymes ubc13", "type enzymes ubc13 and", "enzymes ubc13 and uev1a", "and uev1a also", "uev1a also known", "also known as ube2v1", "ube2v1 traf6", "traf6 catalyses lys63 linked", "catalyses lys63 linked ubiquitination.", "lys63 linked ubiquitination. it", "linked ubiquitination. it is", "ubiquitination. it is believed", "it is believed that", "is believed that auto", "believed that auto polyubiquitination", "auto polyubiquitination and", "polyubiquitination and oligomerization", "and oligomerization of traf6", "oligomerization of traf6 is", "of traf6 is followed", "traf6 is followed by", "is followed by binding", "followed by binding the", "by binding the ubiquitin", "binding the ubiquitin receptors", "the ubiquitin receptors of", "ubiquitin receptors of tab2", "receptors of tab2 or", "of tab2 or tab3", "or tab3 tak1", "tab3 tak1 binding", "tak1 binding protein 2", "binding protein 2 and", "protein 2 and 3", "3 which", "which stimulates phosphorylation and", "stimulates phosphorylation and activation", "phosphorylation and activation of", "and activation of tgf", "activation of tgf beta", "of tgf beta activated", "tgf beta activated kinase", "beta activated kinase 1", "activated kinase 1 tak1", "kinase 1 tak1 .

tak1", "1 tak1 .

tak1 phosphorylates", "tak1 .

tak1 phosphorylates ikk", ".

tak1 phosphorylates ikk alpha", "phosphorylates ikk alpha and", "ikk alpha and ikk", "alpha and ikk beta", "ikk beta which", "beta which in", "which in turn phosphorylate", "in turn phosphorylate nf", "turn phosphorylate nf kb", "phosphorylate nf kb inhibitors", "inhibitors ikb", "ikb and eventually", "and eventually results in", "eventually results in ikb", "results in ikb degradation", "in ikb degradation and", "ikb degradation and nf", "degradation and nf kb", "and nf kb translocation", "nf kb translocation to", "kb translocation to the", "translocation to the nucleus.", "to the nucleus. also", "the nucleus. also tak1", "nucleus. also tak1 mediates", "also tak1 mediates jnk", "tak1 mediates jnk and", "mediates jnk and p38", "jnk and p38 map", "and p38 map kinases", "p38 map kinases activation", "map kinases activation by", "kinases activation by phosphorylating", "activation by phosphorylating mkk4/7", "by phosphorylating mkk4/7 and", "phosphorylating mkk4/7 and mkk3/6", "mkk4/7 and mkk3/6 respectivly", "and mkk3/6 respectivly resulting", "mkk3/6 respectivly resulting in", "respectivly resulting in the", "resulting in the activation", "in the activation of", "the activation of many", "activation of many transcription", "of many transcription factors.", "many transcription factors.

the", "transcription factors.

the role", "factors.

the role of", "

the role of traf6", "role of traf6 is", "of traf6 is somewhat", "traf6 is somewhat controversial", "is somewhat controversial and", "somewhat controversial and probably", "controversial and probably cell", "and probably cell type", "probably cell type specific.", "cell type specific. traf6", "type specific. traf6 autoubiquitination", "specific. traf6 autoubiquitination was", "traf6 autoubiquitination was found", "autoubiquitination was found to", "was found to be", "found to be dispensable", "to be dispensable for", "be dispensable for traf6", "dispensable for traf6 function", "for traf6 function to", "traf6 function to activate", "function to activate tak1", "to activate tak1 pathway.", "activate tak1 pathway. these", "tak1 pathway. these findings", "pathway. these findings are", "these findings are consistent", "findings are consistent with", "are consistent with the", "consistent with the new", "with the new mechanism", "the new mechanism of", "new mechanism of traf6", "mechanism of traf6 mediated", "of traf6 mediated nf", "traf6 mediated nf kb", "mediated nf kb activation", "nf kb activation that", "kb activation that was", "activation that was suggested", "that was suggested by", "was suggested by xia", "suggested by xia et", "by xia et al.", "et al. 2009", "al. 2009 .", "2009 . traf6 generates", ". traf6 generates unanchored", "traf6 generates unanchored lys63", "generates unanchored lys63 linked", "unanchored lys63 linked polyubiquitin", "lys63 linked polyubiquitin chains", "linked polyubiquitin chains that", "polyubiquitin chains that bind", "chains that bind to", "that bind to the", "bind to the regulatory", "to the regulatory subunits", "the regulatory subunits of", "regulatory subunits of tak1", "of tak1 tab2", "tak1 tab2 or", "or tab3 and", "tab3 and ikk", "nemo leading", "leading to the activation", "to the activation of", "the activation of the", "activation of the kinases.

", "of the kinases.

xia", "the kinases.

xia et", "kinases.

xia et al.", "2009 demonstrated in", "demonstrated in vitro that", "in vitro that unlike", "vitro that unlike polyubiquitin", "that unlike polyubiquitin chains", "unlike polyubiquitin chains covalently", "polyubiquitin chains covalently attached", "chains covalently attached to", "covalently attached to traf6", "attached to traf6 or", "to traf6 or irak", "or irak tab2", "irak tab2 and", "tab2 and nemo associated", "and nemo associated ubiquitin", "nemo associated ubiquitin chains", "associated ubiquitin chains were", "ubiquitin chains were found", "chains were found to", "were found to be", "found to be unanchored", "to be unanchored and", "be unanchored and susceptible", "unanchored and susceptible to", "and susceptible to n", "susceptible to n terminal", "to n terminal ubiquitin", "n terminal ubiquitin cleavage.", "terminal ubiquitin cleavage. only", "ubiquitin cleavage. only k63", "cleavage. only k63 linked", "only k63 linked polyubiquitin", "k63 linked polyubiquitin chains", "polyubiquitin chains but", "chains but not", "but not monomeric ubiquitin", "monomeric ubiquitin activated", "ubiquitin activated tak1", "activated tak1 in a", "tak1 in a dose", "in a dose dependent", "a dose dependent manner.", "dose dependent manner. optimal", "dependent manner. optimal activation", "manner. optimal activation of", "optimal activation of the", "activation of the ikk", "of the ikk complex", "the ikk complex was", "ikk complex was achieved", "complex was achieved using", "was achieved using ubiquitin", "achieved using ubiquitin polymers", "using ubiquitin polymers containing", "ubiquitin polymers containing both", "polymers containing both k48", "containing both k48 and", "both k48 and k63", "k48 and k63 linkages.

furthermore", "k63 linkages.

furthermore the", "linkages.

furthermore the authors", "the authors proposed that", "authors proposed that the", "proposed that the tak1", "that the tak1 complexes", "the tak1 complexes might", "tak1 complexes might be", "complexes might be brougt", "might be brougt in", "be brougt in close", "brougt in close proximity", "in close proximity by", "close proximity by binding", "proximity by binding several", "by binding several tab2/3", "binding several tab2/3 to", "several tab2/3 to a", "tab2/3 to a single", "to a single polyubiquitin", "a single polyubiquitin chain", "single polyubiquitin chain to", "polyubiquitin chain to facilitate", "chain to facilitate tak1", "to facilitate tak1 kinase", "facilitate tak1 kinase trans", "tak1 kinase trans phosphorylation.", "kinase trans phosphorylation. alternativly", "phosphorylation. alternativly the", "alternativly the possibility", "the possibility that polyub", "possibility that polyub binding", "that polyub binding promotes", "polyub binding promotes allosteric", "binding promotes allosteric activation", "promotes allosteric activation of", "allosteric activation of tak1", "activation of tak1 complex", "of tak1 complex should", "complex should be", "should be considered", "be considered walsh", "considered walsh et", "walsh et al 2008", "et al 2008 .", "in human together with", "human together with ubiquitin", "together with ubiquitin conjugating e2", "with ubiquitin conjugating e2 type", "ubiquitin conjugating e2 type enzymes", "conjugating e2 type enzymes ubc13", "e2 type enzymes ubc13 and", "type enzymes ubc13 and uev1a", "ubc13 and uev1a also", "and uev1a also known", "uev1a also known as", "as ube2v1 traf6", "ube2v1 traf6 catalyses", "traf6 catalyses lys63 linked ubiquitination.", "catalyses lys63 linked ubiquitination. it", "lys63 linked ubiquitination. it is", "linked ubiquitination. it is believed", "ubiquitination. it is believed that", "it is believed that auto", "is believed that auto polyubiquitination", "that auto polyubiquitination and", "auto polyubiquitination and oligomerization", "polyubiquitination and oligomerization of", "and oligomerization of traf6 is", "oligomerization of traf6 is followed", "of traf6 is followed by", "traf6 is followed by binding", "is followed by binding the", "followed by binding the ubiquitin", "by binding the ubiquitin receptors", "binding the ubiquitin receptors of", "the ubiquitin receptors of tab2", "ubiquitin receptors of tab2 or", "receptors of tab2 or tab3", "tab2 or tab3 tak1", "or tab3 tak1 binding", "tab3 tak1 binding protein", "tak1 binding protein 2 and", "binding protein 2 and 3", "and 3 which", "3 which stimulates", "which stimulates phosphorylation and activation", "stimulates phosphorylation and activation of", "phosphorylation and activation of tgf", "and activation of tgf beta", "activation of tgf beta activated", "of tgf beta activated kinase", "tgf beta activated kinase 1", "beta activated kinase 1 tak1", "activated kinase 1 tak1 .

tak1", "kinase 1 tak1 .

tak1 phosphorylates", "1 tak1 .

tak1 phosphorylates ikk", "tak1 .

tak1 phosphorylates ikk alpha", ".

tak1 phosphorylates ikk alpha and", "phosphorylates ikk alpha and ikk", "ikk alpha and ikk beta", "and ikk beta which", "ikk beta which in", "beta which in turn", "which in turn phosphorylate nf", "in turn phosphorylate nf kb", "turn phosphorylate nf kb inhibitors", "kb inhibitors ikb", "ikb and eventually results", "and eventually results in ikb", "eventually results in ikb degradation", "results in ikb degradation and", "in ikb degradation and nf", "ikb degradation and nf kb", "degradation and nf kb translocation", "and nf kb translocation to", "nf kb translocation to the", "kb translocation to the nucleus.", "translocation to the nucleus. also", "to the nucleus. also tak1", "the nucleus. also tak1 mediates", "nucleus. also tak1 mediates jnk", "also tak1 mediates jnk and", "tak1 mediates jnk and p38", "mediates jnk and p38 map", "jnk and p38 map kinases", "and p38 map kinases activation", "p38 map kinases activation by", "map kinases activation by phosphorylating", "kinases activation by phosphorylating mkk4/7", "activation by phosphorylating mkk4/7 and", "by phosphorylating mkk4/7 and mkk3/6", "phosphorylating mkk4/7 and mkk3/6 respectivly", "mkk4/7 and mkk3/6 respectivly resulting", "and mkk3/6 respectivly resulting in", "mkk3/6 respectivly resulting in the", "respectivly resulting in the activation", "resulting in the activation of", "in the activation of many", "the activation of many transcription", "activation of many transcription factors.", "of many transcription factors.

the", "many transcription factors.

the role", "transcription factors.

the role of", "factors.

the role of traf6", "

the role of traf6 is", "role of traf6 is somewhat", "of traf6 is somewhat controversial", "traf6 is somewhat controversial and", "is somewhat controversial and probably", "somewhat controversial and probably cell", "controversial and probably cell type", "and probably cell type specific.", "probably cell type specific. traf6", "cell type specific. traf6 autoubiquitination", "type specific. traf6 autoubiquitination was", "specific. traf6 autoubiquitination was found", "traf6 autoubiquitination was found to", "autoubiquitination was found to be", "was found to be dispensable", "found to be dispensable for", "to be dispensable for traf6", "be dispensable for traf6 function", "dispensable for traf6 function to", "for traf6 function to activate", "traf6 function to activate tak1", "function to activate tak1 pathway.", "to activate tak1 pathway. these", "activate tak1 pathway. these findings", "tak1 pathway. these findings are", "pathway. these findings are consistent", "these findings are consistent with", "findings are consistent with the", "are consistent with the new", "consistent with the new mechanism", "with the new mechanism of", "the new mechanism of traf6", "new mechanism of traf6 mediated", "mechanism of traf6 mediated nf", "of traf6 mediated nf kb", "traf6 mediated nf kb activation", "mediated nf kb activation that", "nf kb activation that was", "kb activation that was suggested", "activation that was suggested by", "that was suggested by xia", "was suggested by xia et", "suggested by xia et al.", "xia et al. 2009", "et al. 2009 .", "al. 2009 . traf6", "2009 . traf6 generates unanchored", ". traf6 generates unanchored lys63", "traf6 generates unanchored lys63 linked", "generates unanchored lys63 linked polyubiquitin", "unanchored lys63 linked polyubiquitin chains", "lys63 linked polyubiquitin chains that", "linked polyubiquitin chains that bind", "polyubiquitin chains that bind to", "chains that bind to the", "that bind to the regulatory", "bind to the regulatory subunits", "to the regulatory subunits of", "the regulatory subunits of tak1", "subunits of tak1 tab2", "of tak1 tab2 or", "tak1 tab2 or tab3", "tab2 or tab3 and", "or tab3 and ikk", "tab3 and ikk nemo", "ikk nemo leading", "nemo leading to", "leading to the activation of", "to the activation of the", "the activation of the kinases.

", "activation of the kinases.

xia", "of the kinases.

xia et", "the kinases.

xia et al.", "al. 2009 demonstrated", "2009 demonstrated in vitro", "demonstrated in vitro that unlike", "in vitro that unlike polyubiquitin", "vitro that unlike polyubiquitin chains", "that unlike polyubiquitin chains covalently", "unlike polyubiquitin chains covalently attached", "polyubiquitin chains covalently attached to", "chains covalently attached to traf6", "covalently attached to traf6 or", "attached to traf6 or irak", "traf6 or irak tab2", "or irak tab2 and", "irak tab2 and nemo", "tab2 and nemo associated ubiquitin", "and nemo associated ubiquitin chains", "nemo associated ubiquitin chains were", "associated ubiquitin chains were found", "ubiquitin chains were found to", "chains were found to be", "were found to be unanchored", "found to be unanchored and", "to be unanchored and susceptible", "be unanchored and susceptible to", "unanchored and susceptible to n", "and susceptible to n terminal", "susceptible to n terminal ubiquitin", "to n terminal ubiquitin cleavage.", "n terminal ubiquitin cleavage. only", "terminal ubiquitin cleavage. only k63", "ubiquitin cleavage. only k63 linked", "cleavage. only k63 linked polyubiquitin", "only k63 linked polyubiquitin chains", "linked polyubiquitin chains but", "polyubiquitin chains but not", "chains but not monomeric", "not monomeric ubiquitin activated", "monomeric ubiquitin activated tak1", "ubiquitin activated tak1 in", "activated tak1 in a dose", "tak1 in a dose dependent", "in a dose dependent manner.", "a dose dependent manner. optimal", "dose dependent manner. optimal activation", "dependent manner. optimal activation of", "manner. optimal activation of the", "optimal activation of the ikk", "activation of the ikk complex", "of the ikk complex was", "the ikk complex was achieved", "ikk complex was achieved using", "complex was achieved using ubiquitin", "was achieved using ubiquitin polymers", "achieved using ubiquitin polymers containing", "using ubiquitin polymers containing both", "ubiquitin polymers containing both k48", "polymers containing both k48 and", "containing both k48 and k63", "both k48 and k63 linkages.

furthermore", "and k63 linkages.

furthermore the", "k63 linkages.

furthermore the authors", "linkages.

furthermore the authors proposed", "the authors proposed that the", "authors proposed that the tak1", "proposed that the tak1 complexes", "that the tak1 complexes might", "the tak1 complexes might be", "tak1 complexes might be brougt", "complexes might be brougt in", "might be brougt in close", "be brougt in close proximity", "brougt in close proximity by", "in close proximity by binding", "close proximity by binding several", "proximity by binding several tab2/3", "by binding several tab2/3 to", "binding several tab2/3 to a", "several tab2/3 to a single", "tab2/3 to a single polyubiquitin", "to a single polyubiquitin chain", "a single polyubiquitin chain to", "single polyubiquitin chain to facilitate", "polyubiquitin chain to facilitate tak1", "chain to facilitate tak1 kinase", "to facilitate tak1 kinase trans", "facilitate tak1 kinase trans phosphorylation.", "tak1 kinase trans phosphorylation. alternativly", "trans phosphorylation. alternativly the", "phosphorylation. alternativly the possibility", "alternativly the possibility that", "the possibility that polyub binding", "possibility that polyub binding promotes", "that polyub binding promotes allosteric", "polyub binding promotes allosteric activation", "binding promotes allosteric activation of", "promotes allosteric activation of tak1", "allosteric activation of tak1 complex", "activation of tak1 complex should", "tak1 complex should be", "complex should be considered", "be considered walsh et", "considered walsh et al", "walsh et al 2008 ." ] }, { "record_id": "GLY_000594_1_663", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9018519", "r hsa", "hsa 9018519", "r hsa 9018519" ] }, { "record_id": "GLY_000594_1_663", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "estrogen dependent", "dependent gene", "gene expression", "estrogen dependent gene", "dependent gene expression", "estrogen dependent gene expression", 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the", "the target", "target gene", "gene promoter", "or indirectly", "indirectly through", "with another", "another dna", "dna binding", "binding protein", "protein such", "such as", "as runx1", "ap1 or", "or nf", "nf kappa", "kappa beta", "reviewed in", "in bai", "bai and", "and gust", "and krause", "2014 .", ". binding", "binding of", "of estrogen", "receptors to", "to the", "the dna", "dna promotes", "promotes the", "the assembly", "assembly of", "of higher", "higher order", "order transcriptional", "transcriptional complexes", "complexes containing", "containing methyltransferases", "histone acetyltransferases", "acetyltransferases and", "and other", "other transcriptional", "transcriptional activators", "which promote", "promote transcription", "transcription by", "by establishing", "establishing active", "active chromatin", "chromatin marks", "marks and", "and by", "by recruiting", "recruiting general", "general transcription", "transcription factors", "factors and", "and rna", 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"appears to", "to be", "be primed", "primed by", "by the", "the binding", "of pioneering", "pioneering transcription", "factors such", "as foxa1", "pbx1 among", "among others.", "others. these", "these factors", "factors bind", "bind to", "to heterochromatin", "heterochromatin by", "by virtue", "virtue of", "of their", "their winged", "winged helix", "helix domains", "domains and", "and promote", "promote chromatin", "chromatin opening", "allowing subsequent", "subsequent recruitment", "of other", "other transcription", "in zaret", "zaret and", "fiorito et", "magnani et", "estrogens mediate their", "mediate their transcriptional", "their transcriptional effects", "transcriptional effects through", "effects through interaction", "through interaction with", "interaction with the", "with the estrogen", "the estrogen receptors", "receptors esr1", "esr1 also", "also known as", "known as er", "as er alpha", "alpha and", "esr2 er", "er beta .", "beta . esr1", ". esr1 and", "esr1 and esr2", "and esr2 share", "esr2 share overlapping", "share overlapping but", "overlapping but distinct", "but distinct functions", "functions with", "with esr1 playing", "esr1 playing the", "playing the primary", "the primary role", "primary role in", "role in transcriptional", "in transcriptional activation", "transcriptional activation in", "activation in most", "in most cell", "most cell types", "types hah", "hah and krauss", "krauss 2014", "2014 haldos\u00e9n", "haldos\u00e9n et al", "al 2014.", "2014. the receptors", "the receptors function", "receptors function as", "function as ligand", "as ligand dependent", "ligand dependent dimers", "dependent dimers and", "dimers and can", "and can activate", "can activate target", "activate target genes", "target genes either", "genes either through", "either through direct", "through direct binding", "direct binding to", "binding to an", "to an estrogen", "an estrogen responsive", "estrogen responsive element", "element ere", "ere in", "in the target", "the target gene", "target gene promoter", "promoter or", "or indirectly through", "indirectly through interaction", "interaction with another", "with another dna", "another dna binding", "dna binding protein", "binding protein such", "protein such as", "such as runx1", "runx1 sp1", "sp1 ap1", "ap1 or nf", "or nf kappa", "nf kappa beta", "beta reviewed", "reviewed in bai", "in bai and", "bai and gust", "gust 2009", "2009 hah", "hah and krause", "krause 2014", "2014 . binding", ". binding of", "binding of estrogen", "of estrogen receptors", "estrogen receptors to", "receptors to the", "to the dna", "the dna promotes", "dna promotes the", "promotes the assembly", "the assembly of", "assembly of higher", "of higher order", "higher order transcriptional", "order transcriptional complexes", "transcriptional complexes containing", "complexes containing methyltransferases", "methyltransferases histone", "histone acetyltransferases and", "acetyltransferases and other", "and other 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"kittler et al", "al 2013", "2013 mohammed", "mohammed et al", "2013 foulds", "foulds et al", "al 2015", "2015 liu", "liu et al", "al 2014", "2014 reviewed", "reviewed in magnani", "in magnani and", "magnani and lupien", "lupien 2014", "2014 arnal", "arnal 2017", "2017 . in", ". in some", "in some circumstances", "circumstances ligand", "ligand bound receptors", "bound receptors can", "receptors can also", "can also promote", "also promote the", "promote the assembly", "assembly of a", "of a repression", "a repression complex", "repression complex at", "complex at a", "at a target", "a target gene", "gene and", "and in some", "in some cases", "cases heterodimers", "heterodimers of esr1", "of esr1 and", "and esr2 serve", "esr2 serve as", "serve as repressors", "as repressors of", "repressors of esr1", "of esr1 mediated", "esr1 mediated target", "mediated target gene", "target gene activation", "activation reviewed", "reviewed in hah", "in hah and", "hah and kraus", "kraus 2014", "arnal et al", "al 2017", ". phosphorylation", "phosphorylation of the", "of the estrogen", "the estrogen receptor", "estrogen receptor also", "receptor also modulates", "also modulates its", "modulates its activity", "activity and", "and provides cross", "provides cross talk", "cross talk between", "talk between nuclear", "between nuclear estrogen", "nuclear estrogen dependent", "estrogen dependent signaling", "dependent signaling and", "signaling and non", "and non genomic", "non genomic estrogen", "genomic estrogen signaling", "estrogen signaling from", "signaling from the", "from the plasma", "the plasma membrane", "membrane reviewed", "reviewed in anbalagan", "in anbalagan and", "anbalagan and rowan", "rowan 2015", "2015 halods\u00e8n", "halods\u00e8n et al", "2014 schwartz", "schwartz et al", "al 2016", "2016

a", "

a number of", "number of recent", "of recent genome", "recent genome wide", "genome wide studies", "wide studies highlight", "studies highlight the", "highlight the breadth", "the breadth of", "breadth of the", "of the transcriptional", "the transcriptional response", "transcriptional response to", "response to estrogen.", "to estrogen. the", "estrogen. the number", "the number of", "number of predicted", "of predicted estrogen", "predicted estrogen dependent", "estrogen dependent target", "dependent target genes", "target genes ranges", "genes ranges from", "ranges from a", "from a couple", "a couple of", "couple of hundred", "hundred based", "based on microarray", "on microarray studies", "studies to", "to upwards of", "upwards of 10000", "10000 based", "based on chip", "on chip chip", "chip chip or", "chip or chip", "or chip seq", "seq cheung", "cheung and kraus", "kraus 2010", "2010 kinnis", "kinnis and kraus", "kraus 2008", "2008 lin", "lin et al", "al 2004", "2004 welboren", "welboren et al", "al 2009", "2009 ikeda", "ikeda et al", "2015 lin", "al 2007", "2007 carroll", "carroll et al", "al 2006", "2006 . many", ". many of", "many of these", "of these predicted", "these predicted sites", "predicted sites may", "sites may not", "may not represent", "not represent transcriptionally", "represent transcriptionally productive", "transcriptionally productive binding", "productive binding events", "events however.", "however. a study", "a study examining", "study examining esr1", "examining esr1 binding", "esr1 binding by", "binding by chip", "by chip seq", "chip seq in", "seq in 20", "in 20 primary", "20 primary breast", "primary breast cancers", "breast cancers identified", "cancers identified a", "identified a core", "a core of", "core of 484", "of 484 esr", "484 esr binding", "esr binding events", "binding events that", "events that were", "that were conserved", "were conserved in", "conserved in at", "in at least", "at least 75%", "least 75% of", "75% of er+", "of er+ tumors", "tumors which", "which may represent", "may represent a", "represent a more", "a more realistic", "more realistic estimate", "estimate ross", "ross innes et", "innes et al", "al 2012", "2012 . these", ". these studies", "these studies also", "studies also highlight", "also highlight the", "highlight the long", "the long range", "long range effect", "range effect of", "effect of estrogen", "of estrogen receptor", "estrogen receptor binding", "binding with", "with distal enhancer", "distal enhancer or", "enhancer or promoter", "or promoter elements", "promoter elements regulating", "elements regulating the", "regulating the expression", "the expression of", "expression of many", "of many target", "many target genes", "genes often", "often through looping", "through looping or", "looping or other", "or other higher", "other higher order", "higher order chromatin", "order chromatin structures", "structures kittler", "2013 reviewed", "reviewed in dietz", "in dietz and", "dietz and carroll", "carroll 2008", "2008 liu", "liu and cheung", "cheung 2014", "2014 magnani", "2014 . transcription", ". transcription from", "transcription from a", "from a number", "a number of", "number of estrogen", "of estrogen responsive", "estrogen responsive target", "responsive target genes", "target genes also", "genes also appears", "also appears to", "appears to be", "to be primed", "be primed by", "primed by the", "by the binding", "the binding of", "binding of pioneering", "of pioneering transcription", "pioneering transcription factors", "transcription factors such", "factors such as", "such as foxa1", "foxa1 gata3", "gata3 pbx1", "pbx1 among others.", "among others. these", "others. these factors", "these factors bind", "factors bind to", "bind to heterochromatin", "to heterochromatin by", "heterochromatin by virtue", "by virtue of", "virtue of their", "of their winged", "their winged helix", "winged helix domains", "helix domains and", "domains and promote", "and promote chromatin", "promote chromatin opening", "opening allowing", "allowing subsequent recruitment", "subsequent recruitment of", "recruitment of other", "of other transcription", "other transcription factors", "factors reviewed", "reviewed in zaret", "in zaret and", "zaret and carroll", "carroll 2011", "2011 fiorito", "fiorito et al", "2013 arnal", "2017 magnani", "magnani et al", "al 2011", "estrogens mediate their transcriptional", "mediate their transcriptional effects", "their transcriptional effects through", "transcriptional effects through interaction", "effects through interaction with", "through interaction with the", "interaction with the estrogen", "with the estrogen receptors", "estrogen receptors esr1", "esr1 also known", "also known as er", "known as er alpha", "er alpha and", "alpha and esr2", "and esr2 er", "esr2 er beta", "er beta . esr1", "beta . esr1 and", ". esr1 and esr2", "esr1 and esr2 share", "and esr2 share overlapping", "esr2 share overlapping but", "share overlapping but distinct", "overlapping but distinct functions", "distinct functions with", "functions with esr1", "with esr1 playing the", "esr1 playing the primary", "playing the primary role", "the primary role in", "primary role in transcriptional", "role in transcriptional activation", "in transcriptional activation in", "transcriptional activation in most", "activation in most cell", "in most cell types", "cell types hah", "types hah and", "and krauss 2014", "2014 haldos\u00e9n et", "et al 2014.", "al 2014. the", "2014. the receptors function", "the receptors function as", "receptors function as ligand", "function as ligand dependent", "as ligand dependent dimers", "ligand dependent dimers and", "dependent dimers and can", "dimers and can activate", "and can activate target", "can activate target genes", "activate target genes either", "target genes either through", "genes either through direct", "either through direct binding", "through direct binding to", "direct binding to an", "binding to an estrogen", "to an estrogen responsive", "an estrogen responsive element", "responsive element ere", "ere in the", "in the target gene", "the target gene promoter", "gene promoter or", "promoter or indirectly", "or indirectly through interaction", "indirectly through interaction with", "through interaction with another", "interaction with another dna", "with another dna binding", "another dna binding protein", "dna binding protein such", "binding protein such as", "protein such as runx1", "as runx1 sp1", "sp1 ap1 or", "ap1 or nf kappa", "or nf kappa beta", "kappa beta reviewed", "beta reviewed in", "reviewed in bai and", "in bai and gust", "and gust 2009", "2009 hah and", "and krause 2014", "krause 2014 .", "2014 . binding of", ". binding of estrogen", "binding of estrogen receptors", "of estrogen receptors to", "estrogen receptors to the", "receptors to the dna", "to the dna promotes", "the dna promotes the", "dna promotes the assembly", "promotes the assembly of", "the assembly of higher", "assembly of higher order", "of higher order transcriptional", "higher order transcriptional complexes", "order transcriptional complexes containing", "transcriptional complexes containing methyltransferases", "containing methyltransferases histone", "methyltransferases histone acetyltransferases", "histone acetyltransferases and other", "acetyltransferases and other transcriptional", "and other transcriptional activators", "transcriptional activators which", "activators which promote", "which promote transcription by", "promote transcription by establishing", "transcription by establishing active", "by establishing active chromatin", "establishing active chromatin marks", "active chromatin marks and", "chromatin marks and by", "marks and by recruiting", "and by recruiting general", "by recruiting general transcription", "recruiting general transcription factors", "general transcription factors and", "transcription factors and rna", "factors and rna polymerase", "and rna polymerase ii.", "rna polymerase ii. esr1", "ii. esr1 and", "esr1 and estrogen", "and estrogen dependent recruitment", "estrogen dependent recruitment of", "dependent recruitment of up", "recruitment of up to", "of up to hundreds", "up to hundreds of", "to hundreds of coregulators", "hundreds of coregulators has", "of coregulators has been", "coregulators has been demonstrated", "has been demonstrated by", "been demonstrated by varied", "demonstrated by varied co", "by varied co immunoprecipitation", "varied co immunoprecipitation and", "co immunoprecipitation and proteomic", "immunoprecipitation and proteomic approaches", "proteomic approaches kittler", "approaches kittler et", "et al 2013", "2013 mohammed et", "2013 foulds et", "et al 2015", "2015 liu et", "et al 2014", "2014 reviewed in", "reviewed in magnani and", "in magnani and lupien", "and lupien 2014", "arnal 2017 .", "2017 . in some", ". in some circumstances", "some circumstances ligand", "circumstances ligand bound", "ligand bound receptors can", "bound receptors can also", "receptors can also promote", "can also promote the", "also promote the assembly", "promote the assembly of", "the assembly of a", "assembly of a repression", "of a repression complex", "a repression complex at", "repression complex at a", "complex at a target", "at a target gene", "target gene and", "gene and in", "and in some cases", "some cases heterodimers", "cases heterodimers of", "heterodimers of esr1 and", "of esr1 and esr2", "esr1 and esr2 serve", "and esr2 serve as", "esr2 serve as repressors", "serve as repressors of", "as repressors of esr1", "repressors of esr1 mediated", "of esr1 mediated target", "esr1 mediated target gene", "mediated target gene activation", "gene activation reviewed", "activation reviewed in", "reviewed in hah and", "in hah and kraus", "and kraus 2014", "2014 arnal et", "et al 2017", "al 2017 .", "2017 . phosphorylation", ". phosphorylation of", "phosphorylation of the estrogen", "of the estrogen receptor", "the estrogen receptor also", "estrogen receptor also modulates", "receptor also modulates its", "also modulates its activity", "its activity and", "activity and provides", "and provides cross talk", "provides cross talk between", "cross talk between nuclear", "talk between nuclear estrogen", "between nuclear estrogen dependent", "nuclear estrogen dependent signaling", "estrogen dependent signaling and", "dependent signaling and non", "signaling and non genomic", "and non genomic estrogen", "non genomic estrogen signaling", "genomic estrogen signaling from", "estrogen signaling from the", "signaling from the plasma", "from the plasma membrane", "plasma membrane reviewed", "membrane reviewed in", "reviewed in anbalagan and", "in anbalagan and rowan", "and rowan 2015", "2015 halods\u00e8n et", "2014 schwartz et", "et al 2016", "2016

a number", "

a number of recent", "number of recent genome", "of recent genome wide", "recent genome wide studies", "genome wide studies highlight", "wide studies highlight the", "studies highlight the breadth", "highlight the breadth of", "the breadth of the", "breadth of the transcriptional", "of the transcriptional response", "the transcriptional response to", "transcriptional response to estrogen.", "response to estrogen. the", "to estrogen. the number", "estrogen. the number of", "the number of predicted", "number of predicted estrogen", "of predicted estrogen dependent", "predicted estrogen dependent target", "estrogen dependent target genes", "dependent target genes ranges", "target genes ranges from", "genes ranges from a", "ranges from a couple", "from a couple of", "a couple of hundred", "of hundred based", "hundred based on", "based on microarray studies", "microarray studies to", "studies to upwards", "to upwards of 10000", "of 10000 based", "10000 based on", "based on chip chip", "on chip chip or", "chip chip or chip", "chip or chip seq", "chip seq cheung", "seq cheung and", "and kraus 2010", "2010 kinnis and", "and kraus 2008", "2008 lin et", "et al 2004", "2004 welboren et", "et al 2009", "2009 ikeda et", "2015 lin et", "et al 2007", "2007 carroll et", "et al 2006", "al 2006 .", "2006 . many of", ". many of these", "many of these predicted", "of these predicted sites", "these predicted sites may", "predicted sites may not", "sites may not represent", "may not represent transcriptionally", "not represent transcriptionally productive", "represent transcriptionally productive binding", "transcriptionally productive binding events", "binding events however.", "events however. a", "however. a study examining", "a study examining esr1", "study examining esr1 binding", "examining esr1 binding by", "esr1 binding by chip", "binding by chip seq", "by chip seq in", "chip seq in 20", "seq in 20 primary", "in 20 primary breast", "20 primary breast cancers", "primary breast cancers identified", "breast cancers identified a", "cancers identified a core", "identified a core of", "a core of 484", "core of 484 esr", "of 484 esr binding", "484 esr binding events", "esr binding events that", "binding events that were", "events that were conserved", "that were conserved in", "were conserved in at", "conserved in at least", "in at least 75%", "at least 75% of", "least 75% of er+", "75% of er+ tumors", "er+ tumors which", "tumors which may", "which may represent a", "may represent a more", "represent a more realistic", "a more realistic estimate", "realistic estimate ross", "estimate ross innes", "ross innes et al", "et al 2012", "al 2012 .", "2012 . these studies", ". these studies also", "these studies also highlight", "studies also highlight the", "also highlight the long", "highlight the long range", "the long range effect", "long range effect of", "range effect of estrogen", "effect of estrogen receptor", "of estrogen receptor binding", "receptor binding with", "binding with distal", "with distal enhancer or", "distal enhancer or promoter", "enhancer or promoter elements", "or promoter elements regulating", "promoter elements regulating the", "elements regulating the expression", "regulating the expression of", "the expression of many", "expression of many target", "of many target genes", "target genes often", "genes often through", "often through looping or", "through looping or other", "looping or other higher", "or other higher order", "other higher order chromatin", "higher order chromatin structures", "chromatin structures kittler", "structures kittler et", "2013 reviewed in", "reviewed in dietz and", "in dietz and carroll", "and carroll 2008", "2008 liu and", "and cheung 2014", "2014 magnani and", "lupien 2014 .", "2014 . transcription from", ". transcription from a", "transcription from a number", "from a number of", "a number of estrogen", "number of estrogen responsive", "of estrogen responsive target", "estrogen responsive target genes", "responsive target genes also", "target genes also appears", "genes also appears to", "also appears to be", "appears to be primed", "to be primed by", "be primed by the", "primed by the binding", "by the binding of", "the binding of pioneering", "binding of pioneering transcription", "of pioneering transcription factors", "pioneering transcription factors such", "transcription factors such as", "factors such as foxa1", "as foxa1 gata3", "gata3 pbx1 among", "pbx1 among others. these", "among others. these factors", "others. these factors bind", "these factors bind to", "factors bind to heterochromatin", "bind to heterochromatin by", "to heterochromatin by virtue", "heterochromatin by virtue of", "by virtue of their", "virtue of their winged", "of their winged helix", "their winged helix domains", "winged helix domains and", "helix domains and promote", "domains and promote chromatin", "and promote chromatin opening", "chromatin opening allowing", "opening allowing subsequent", "allowing subsequent recruitment of", "subsequent recruitment of other", "recruitment of other transcription", "of other transcription factors", "transcription factors reviewed", "factors reviewed in", "reviewed in zaret and", "in zaret and carroll", "and carroll 2011", "2011 fiorito et", "2013 arnal et", "2017 magnani et", "et al 2011", "estrogens mediate their transcriptional effects", "mediate their transcriptional effects through", "their transcriptional effects through interaction", "transcriptional effects through interaction with", "effects through interaction with the", "through interaction with the estrogen", "interaction with the estrogen receptors", "the estrogen receptors esr1", "receptors esr1 also", "esr1 also known as", "also known as er alpha", "as er alpha and", "er alpha and esr2", "and esr2 er beta", "esr2 er beta .", "er beta . esr1 and", "beta . esr1 and esr2", ". esr1 and esr2 share", "esr1 and esr2 share overlapping", "and esr2 share overlapping but", "esr2 share overlapping but distinct", "share overlapping but distinct functions", "but distinct functions with", "distinct functions with esr1", "functions with esr1 playing", "with esr1 playing the primary", "esr1 playing the primary role", "playing the primary role in", "the primary role in transcriptional", "primary role in transcriptional activation", "role in transcriptional activation in", "in transcriptional activation in most", "transcriptional activation in most cell", "activation in most cell types", "most cell types hah", "cell types hah and", "types hah and krauss", "hah and krauss 2014", "krauss 2014 haldos\u00e9n", "2014 haldos\u00e9n et al", "haldos\u00e9n et al 2014.", "et al 2014. the", "al 2014. the receptors", "2014. the receptors function as", "the receptors function as ligand", "receptors function as ligand dependent", "function as ligand dependent dimers", "as ligand dependent dimers and", "ligand dependent dimers and can", "dependent dimers and can activate", "dimers and can activate target", "and can activate target genes", "can activate target genes either", "activate target genes either through", "target genes either through direct", "genes either through direct binding", "either through direct binding to", "through direct binding to an", "direct binding to an estrogen", "binding to an estrogen responsive", "to an estrogen responsive element", "estrogen responsive element ere", "element ere in", "ere in the target", "in the target gene promoter", "target gene promoter or", "gene promoter or indirectly", "promoter or indirectly through", "or indirectly through interaction with", "indirectly through interaction with another", "through interaction with another dna", "interaction with another dna binding", "with another dna binding protein", "another dna binding protein such", "dna binding protein such as", "binding protein such as runx1", "such as runx1 sp1", "runx1 sp1 ap1", "sp1 ap1 or nf", "ap1 or nf kappa beta", "nf kappa beta reviewed", "kappa beta reviewed in", "beta reviewed in bai", "reviewed in bai and gust", "bai and gust 2009", "gust 2009 hah", "2009 hah and krause", "hah and krause 2014", "and krause 2014 .", "krause 2014 . binding", "2014 . binding of estrogen", ". binding of estrogen receptors", "binding of estrogen receptors to", "of estrogen receptors to the", "estrogen receptors to the dna", "receptors to the dna promotes", "to the dna promotes the", "the dna promotes the assembly", "dna promotes the assembly of", "promotes the assembly of higher", "the assembly of higher order", "assembly of higher order transcriptional", "of higher order transcriptional complexes", "higher order transcriptional complexes containing", "order transcriptional complexes containing methyltransferases", "complexes containing methyltransferases histone", "containing methyltransferases histone acetyltransferases", "methyltransferases histone acetyltransferases and", "histone acetyltransferases and other transcriptional", "acetyltransferases and other transcriptional activators", "other transcriptional activators which", "transcriptional activators which promote", "activators which promote transcription", "which promote transcription by establishing", "promote transcription by establishing active", "transcription by establishing active chromatin", "by establishing active chromatin marks", "establishing active chromatin marks and", "active chromatin marks and by", "chromatin marks and by recruiting", "marks and by recruiting general", "and by recruiting general transcription", "by recruiting general transcription factors", "recruiting general transcription factors and", "general transcription factors and rna", "transcription factors and rna polymerase", "factors and rna polymerase ii.", "and rna polymerase ii. esr1", "polymerase ii. esr1 and", "ii. esr1 and estrogen", "esr1 and estrogen dependent", "and estrogen dependent recruitment of", "estrogen dependent recruitment of up", "dependent recruitment of up to", "recruitment of up to hundreds", "of up to hundreds of", "up to hundreds of coregulators", "to hundreds of coregulators has", "hundreds of coregulators has been", "of coregulators has been demonstrated", "coregulators has been demonstrated by", "has been demonstrated by varied", "been demonstrated by varied co", "demonstrated by varied co immunoprecipitation", "by varied co immunoprecipitation and", "varied co immunoprecipitation and proteomic", "co immunoprecipitation and proteomic approaches", "and proteomic approaches kittler", "proteomic approaches kittler et", "approaches kittler et al", "kittler et al 2013", "al 2013 mohammed", "2013 mohammed et al", "mohammed et al 2013", "al 2013 foulds", "2013 foulds et al", "foulds et al 2013", "mohammed et al 2015", "al 2015 liu", "2015 liu et al", "liu et al 2014", "al 2014 reviewed", "2014 reviewed in magnani", "reviewed in magnani and lupien", "magnani and lupien 2014", "lupien 2014 arnal", "2014 arnal 2017", "arnal 2017 . in", "2017 . in some circumstances", "in some circumstances ligand", "some circumstances ligand bound", "circumstances ligand bound receptors", "ligand bound receptors can also", "bound receptors can also promote", "receptors can also promote the", "can also promote the assembly", "also promote the assembly of", "promote the assembly of a", "the assembly of a repression", "assembly of a repression complex", "of a repression complex at", "a repression complex at a", "repression complex at a target", "complex at a target gene", "a target gene and", "target gene and in", "gene and in some", "in some cases heterodimers", "some cases heterodimers of", "cases heterodimers of esr1", "heterodimers of esr1 and esr2", "of esr1 and esr2 serve", "esr1 and esr2 serve as", "and esr2 serve as repressors", "esr2 serve as repressors of", "serve as repressors of esr1", "as repressors of esr1 mediated", "repressors of esr1 mediated target", "of esr1 mediated target gene", "esr1 mediated target gene activation", "target gene activation reviewed", "gene activation reviewed in", "activation reviewed in hah", "reviewed in hah and kraus", "hah and kraus 2014", "kraus 2014 arnal", "2014 arnal et al", "arnal et al 2017", "et al 2017 .", "2017 . phosphorylation of", ". phosphorylation of the", "phosphorylation of the estrogen receptor", "of the estrogen receptor also", "the estrogen receptor also modulates", "estrogen receptor also modulates its", "receptor also modulates its activity", "modulates its activity and", "its activity and provides", "activity and provides cross", "and provides cross talk between", "provides cross talk between nuclear", "cross talk between nuclear estrogen", "talk between nuclear estrogen dependent", "between nuclear estrogen dependent signaling", "nuclear estrogen dependent signaling and", "estrogen dependent signaling and non", "dependent signaling and non genomic", "signaling and non genomic estrogen", "and non genomic estrogen signaling", "non genomic estrogen signaling from", "genomic estrogen signaling from the", "estrogen signaling from the plasma", "signaling from the plasma membrane", "the plasma membrane reviewed", "plasma membrane reviewed in", "membrane reviewed in anbalagan", "reviewed in anbalagan and rowan", "anbalagan and rowan 2015", "rowan 2015 halods\u00e8n", "2015 halods\u00e8n et al", "halods\u00e8n et al 2014", "al 2014 schwartz", "2014 schwartz et al", "schwartz et al 2016", "al 2016

a", "2016

a number of", "

a number of recent genome", "number of recent genome wide", "of recent genome wide studies", "recent genome wide studies highlight", "genome wide studies highlight the", "wide studies highlight the breadth", "studies highlight the breadth of", "highlight the breadth of the", "the breadth of the transcriptional", "breadth of the transcriptional response", "of the transcriptional response to", "the transcriptional response to estrogen.", "transcriptional response to estrogen. the", "response to estrogen. the number", "to estrogen. the number of", "estrogen. the number of predicted", "the number of predicted estrogen", "number of predicted estrogen dependent", "of predicted estrogen dependent target", "predicted estrogen dependent target genes", "estrogen dependent target genes ranges", "dependent target genes ranges from", "target genes ranges from a", "genes ranges from a couple", "ranges from a couple of", "from a couple of hundred", "couple of hundred based", "of hundred based on", "hundred based on microarray", "on microarray studies to", "microarray studies to upwards", "studies to upwards of", "upwards of 10000 based", "of 10000 based on", "10000 based on chip", "based on chip chip or", "on chip chip or chip", "chip chip or chip seq", "or chip seq cheung", "chip seq cheung and", "seq cheung and kraus", "cheung and kraus 2010", "kraus 2010 kinnis", "2010 kinnis and kraus", "kinnis and kraus 2008", "kraus 2008 lin", "2008 lin et al", "lin et al 2004", "al 2004 welboren", "2004 welboren et al", "welboren et al 2009", "al 2009 ikeda", "2009 ikeda et al", "ikeda et al 2015", "al 2015 lin", "2015 lin et al", "lin et al 2007", "al 2007 carroll", "2007 carroll et al", "carroll et al 2006", "et al 2006 .", "al 2006 . many", "2006 . many of these", ". many of these predicted", "many of these predicted sites", "of these predicted sites may", "these predicted sites may not", "predicted sites may not represent", "sites may not represent transcriptionally", "may not represent transcriptionally productive", "not represent transcriptionally productive binding", "represent transcriptionally productive binding events", "productive binding events however.", "binding events however. a", "events however. a study", "however. a study examining esr1", "a study examining esr1 binding", "study examining esr1 binding by", "examining esr1 binding by chip", "esr1 binding by chip seq", "binding by chip seq in", "by chip seq in 20", "chip seq in 20 primary", "seq in 20 primary breast", "in 20 primary breast cancers", "20 primary breast cancers identified", "primary breast cancers identified a", "breast cancers identified a core", "cancers identified a core of", "identified a core of 484", "a core of 484 esr", "core of 484 esr binding", "of 484 esr binding events", "484 esr binding events that", "esr binding events that were", "binding events that were conserved", "events that were conserved in", "that were conserved in at", "were conserved in at least", "conserved in at least 75%", "in at least 75% of", "at least 75% of er+", "least 75% of er+ tumors", "of er+ tumors which", "er+ tumors which may", "tumors which may represent", "which may represent a more", "may represent a more realistic", "represent a more realistic estimate", "more realistic estimate ross", "realistic estimate ross innes", "estimate ross innes et", "innes et al 2012", "et al 2012 .", "al 2012 . these", "2012 . these studies also", ". these studies also highlight", "these studies also highlight the", "studies also highlight the long", "also highlight the long range", "highlight the long range effect", "the long range effect of", "long range effect of estrogen", "range effect of estrogen receptor", "effect of estrogen receptor binding", "estrogen receptor binding with", "receptor binding with distal", "binding with distal enhancer", "with distal enhancer or promoter", "distal enhancer or promoter elements", "enhancer or promoter elements regulating", "or promoter elements regulating the", "promoter elements regulating the expression", "elements regulating the expression of", "regulating the expression of many", "the expression of many target", "expression of many target genes", "many target genes often", "target genes often through", "genes often through looping", "often through looping or other", "through looping or other higher", "looping or other higher order", "or other higher order chromatin", "other higher order chromatin structures", "order chromatin structures kittler", "chromatin structures kittler et", "structures kittler et al", "al 2013 reviewed", "2013 reviewed in dietz", "reviewed in dietz and carroll", "dietz and carroll 2008", "carroll 2008 liu", "2008 liu and cheung", "liu and cheung 2014", "cheung 2014 magnani", "2014 magnani and lupien", "and lupien 2014 .", "lupien 2014 . transcription", "2014 . transcription from a", ". transcription from a number", "transcription from a number of", "from a number of estrogen", "a number of estrogen responsive", "number of estrogen responsive target", "of estrogen responsive target genes", "estrogen responsive target genes also", "responsive target genes also appears", "target genes also appears to", "genes also appears to be", "also appears to be primed", "appears to be primed by", "to be primed by the", "be primed by the binding", "primed by the binding of", "by the binding of pioneering", "the binding of pioneering transcription", "binding of pioneering transcription factors", "of pioneering transcription factors such", "pioneering transcription factors such as", "transcription factors such as foxa1", "such as foxa1 gata3", "foxa1 gata3 pbx1", "gata3 pbx1 among others.", "pbx1 among others. these factors", "among others. these factors bind", "others. these factors bind to", "these factors bind to heterochromatin", "factors bind to heterochromatin by", "bind to heterochromatin by virtue", "to heterochromatin by virtue of", "heterochromatin by virtue of their", "by virtue of their winged", "virtue of their winged helix", "of their winged helix domains", "their winged helix domains and", "winged helix domains and promote", "helix domains and promote chromatin", "domains and promote chromatin opening", "promote chromatin opening allowing", "chromatin opening allowing subsequent", "opening allowing subsequent recruitment", "allowing subsequent recruitment of other", "subsequent recruitment of other transcription", "recruitment of other transcription factors", "other transcription factors reviewed", "transcription factors reviewed in", "factors reviewed in zaret", "reviewed in zaret and carroll", "zaret and carroll 2011", "carroll 2011 fiorito", "2011 fiorito et al", "fiorito et al 2013", "al 2013 arnal", "2013 arnal et al", "al 2017 magnani", "2017 magnani et al", "magnani et al 2011" ] }, { "record_id": "GLY_000594_1_664", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020702", "r hsa", "hsa 9020702", "r hsa 9020702" ] }, { "record_id": "GLY_000594_1_664", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 1", "1 signaling", "interleukin 1 signaling", "signals via", "via interleukin", "1 receptor", "receptor 1", "the only", "only signaling", "signaling capable", "capable il1", "il1 receptor.", "receptor. this", "this is", "is a", "a single", "single chain", "chain type", "type 1", "1 transmembrane", "transmembrane protein", "protein comprising", "comprising an", "an extracellular", "extracellular ligand", "ligand binding", "binding domain", "domain and", "and an", "an intracellular", "region called", "called the", "the toll/interleukin", "toll/interleukin 1", "domain that", "that is", "is structurally", "structurally conserved", "conserved and", "and shared", "shared by", "by other", "other members", "members of", "of the", "the two", "two families", "families of", "of receptors", "xu et", "et al.", "al. 2000", "2000 .", ". this", "this domain", "domain is", "is also", "also shared", "by the", "the downstream", "downstream adapter", "adapter molecule", "molecule myd88.", "myd88. il1", "il1 binding", "binding to", "to il1r1", "il1r1 leads", "leads to", "to the", "the recruitment", "recruitment of", "of a", "a second", "second receptor", "receptor chain", "chain termed", "termed the", "the il1", "il1 receptor", "receptor accessory", "accessory protein", "il1rap or", "or il1racp", "enabling the", "the formation", "formation of", "a high", "high affinity", "affinity ligand", "ligand receptor", "receptor complex", "complex that", "is capable", "capable of", "of signal", "signal transduction.", "transduction. intracellular", "intracellular signaling", "signaling is", "is initiated", "initiated by", "of myd88", "myd88 to", "the il", "il 1r1/il1rap", "1r1/il1rap complex.", "complex. il1rap", "il1rap is", "is only", "only recruited", "recruited to", "il1r1 when", "when il1", "il1 is", "is present", "it is", "is believed", "believed that", "that a", "a tir", "tir domain", "domain signaling", "signaling complex", "complex is", "is formed", "formed between", "between the", "the receptor", "receptor and", "and the", "the adapter", "adapter tir", "tir domains.", "domains. the", "myd88 leads", "of interleukin", "receptor associated", "associated kinase", "1 and", "probably via", "via their", "their death", "death domains.", "domains. irak4", "irak4 then", "then activates", "activates irak1", "allowing irak1", "irak1 to", "to autophosphorylate.", "autophosphorylate. both", "both irak1", "irak1 and", "and irak4", "then dissociate", "dissociate from", "from myd88", "brikos et", "al. 2007", "which remains", "remains stably", "stably complexed", "complexed with", "with il", "il 1r1", "1r1 and", "and il1rap.", "il1rap. they", "they in", "in turn", "turn interact", "interact with", "with tumor", "tumor necrosis", "necrosis factor", "factor receptor", "associated factor", "factor 6", "which is", "is an", "an e3", "e3 ubiquitin", "ubiquitin ligase", "deng et", ". traf6", "traf6 is", "is then", "then thought", "thought to", "to auto", "auto ubiquinate", "attaching k63", "k63 polyubiquitin", "polyubiquitin to", "to itself", "itself with", "with the", "the assistance", "assistance of", "the e2", "e2 conjugating", "conjugating complex", "complex ubc13/uev1a.", "ubc13/uev1a. k63", "k63 pub", "pub traf6", "traf6 recruits", "recruits transforming", "transforming growth", "growth factor", "beta activated", "activated protein", "protein kinase", "kinase 1", "in a", "a complex", "complex with", "with tak1", "tak1 binding", "binding protein", "protein 2", "and tab3", "which both", "both contain", "contain nuclear", "nuclear zinc", "zinc finger", "finger motifs", "motifs that", "that interact", "with k63", "polyubiquitin chains", "ninomiya tsuji", "tsuji et", "al. 1999", "1999 .", "this activates", "activates tak1", "which then", "inhibitor of", "of nf", "nf kappab", "kinase 2", "ikk2 or", "or ikkb", "within the", "the ikk", "ikk complex", "the kinase", "kinase responsible", "responsible for", "for phosphorylation", "phosphorylation of", "of ikappab.", "ikappab. the", "complex also", "also contains", "contains the", "the scaffold", "scaffold protein", "protein nf", "nf kappa", "kappa b", "b essential", "essential modulator", "nemo .", ". tak1", "tak1 also", "also couples", "couples to", "the upstream", "upstream kinases", "kinases for", "for p38", "p38 and", "and c", "c jun", "jun n", "n terminal", "terminal kinase", "jnk .", ". irak1", "irak1 undergoes", "undergoes k63", "k63 linked", "linked polyubiquination", "pellino e3", "e3 ligases", "ligases are", "are important", "important in", "in this", "this process.", "butler et", "ordureau et", "al. 2008", "2008 .", ". the", "the activity", "activity of", "of these", "these proteins", "proteins is", "is greatly", "greatly enhanced", "enhanced by", "by irak", "irak phosphorylation", "schauvliege et", "al. 2006", "leading to", "to k63", "linked polyubiquitination", "polyubiquitination of", "of irak1.", "irak1. this", "this recruits", "recruits nemo", "nemo to", "to irak1", "with nemo", "nemo binding", "to polyubiquitin", "conze et", "2008 .

tak1", ".

tak1 activates", "activates ikkb", "and ikk", "resulting in", "in phosphorylation", "the inhibitory", "inhibitory ikb", "ikb proteins", "proteins and", "and enabling", "enabling translocation", "translocation of", "of nfkb", "nfkb to", "the nucleus", "ikkb also", "also phosphorylates", "phosphorylates nfkb", "nfkb p105", "to its", "its degradation", "degradation and", "the subsequent", "subsequent release", "release of", "of active", "active tpl2", "tpl2 that", "that triggers", "triggers the", "the extracellular", "extracellular signal", "signal regulated", "regulated kinase", "erk 1/2", "1/2 mapk", "mapk cascade.", "cascade. tak1", "tak1 can", "can also", "also trigger", "trigger the", "the p38", "and jnk", "jnk mapk", "mapk pathways", "pathways via", "via activating", "activating the", "upstream mkks3", "4 and", "and 6.", "6. the", "the mapk", "pathways activate", "activate a", "a number", "number of", "of downstream", "downstream kinases", "kinases and", "and transcription", "transcription factors", "factors that", "that co", "co operate", "operate with", "with nfkb", "to induce", "induce the", "the expression", "expression of", "a range", "range of", "of tlr/il", "tlr/il 1r", "1r responsive", "responsive genes.", "genes. there", "there are", "are reports", "reports suggesting", "suggesting that", "that il1", "il1 stimulation", "stimulation increases", "increases nuclear", "nuclear localization", "localization of", "of irak1", "bol et", "and that", "that nuclear", "nuclear irak1", "irak1 binds", "binds to", "the promoter", "promoter of", "nfkb regulated", "regulated gene", "gene and", "and ikba", "enhancing binding", "binding of", "the nfkb", "nfkb p65", "p65 subunit", "subunit to", "to nfkb", "nfkb responsive", "responsive elements", "elements within", "the ikba", "ikba promoter.", "irak1 is", "is required", "required for", "for il1", "il1 induced", "induced ser", "ser 10", "10 phosphorylation", "of histone", "histone h3", "h3 in", "in vivo", "liu et", ". however", "details of", "of this", "this aspect", "aspect of", "irak1 signaling", "signaling mechanisms", "mechanisms remain", "remain unclear.", "unclear. interleukin", "interleukin 18", "18 is", "is another", "another interleukin", "1 related", "related cytokine", "cytokine which", "which signals", "signals through", "through il18r", "il18r and", "and il18rap", "il18rap subunit", "subunit receptors", "which share", "share homology", "homology with", "with il1r", "il1r and", "and il1rap", "il1rap in", "in the", "the cytokine", "cytokine signaling", "signaling cascade", "cascade .", ". later", "later it", "it follows", "follows a", "a myd88/irak1/traf6", "myd88/irak1/traf6 cascade", "cascade signaling", "signaling until", "until reach", "reach the", "nfkb activation", "moller et", "al. 2002", "2002 .", ". interleukin", "interleukin 33", "37 and", "and 38", "38 are", "are relatively", "relatively recently", "recently discovered", "discovered interleukin", "related citokines", "citokines which", "which are", "are also", "also able", "able to", "to signal", "signal through", "through il1", "receptor subunits", "subunits or", "or other", "other as", "as il18r", "schmitz et", "al. 2005", "yi et", "al. 2016", "lunding et", "al. 2015", "van de", "de veendorck", "veendorck et", "al. 2012", "lin et", "al. 2001", "2001 .", "1 il1", "il1 signals", "signals via interleukin", "via interleukin 1", "interleukin 1 receptor", "1 receptor 1", "1 il1r1", "the only signaling", "only signaling capable", "signaling capable il1", "capable il1 receptor.", "il1 receptor. this", "receptor. this is", "this is a", "is a single", "a single chain", "single chain type", "chain type 1", "type 1 transmembrane", "1 transmembrane protein", "transmembrane protein comprising", "protein comprising an", "comprising an extracellular", "an extracellular ligand", "extracellular ligand binding", "ligand binding domain", "binding domain and", "domain and an", "and an intracellular", "intracellular region", "region called the", "called the toll/interleukin", "the toll/interleukin 1", "toll/interleukin 1 receptor", "receptor tir", "domain that is", "that is structurally", "is structurally conserved", "structurally conserved and", "conserved and shared", "and shared by", "shared by other", "by other members", "other members of", "members of the", "of the two", "the two families", "two families of", "families of receptors", "receptors xu", "xu et al.", "et al. 2000", "al. 2000 .", "2000 . this", ". this domain", "this domain is", "domain is also", "is also shared", "also shared by", "shared by the", "by the downstream", "the downstream adapter", "downstream adapter molecule", "adapter molecule myd88.", "molecule myd88. il1", "myd88. il1 binding", "il1 binding to", "binding to il1r1", "to il1r1 leads", "il1r1 leads to", "leads to the", "to the recruitment", "the recruitment of", "recruitment of a", "of a second", "a second receptor", "second receptor chain", "receptor chain termed", "chain termed the", "termed the il1", "the il1 receptor", "il1 receptor accessory", "receptor accessory protein", "protein il1rap", "il1rap or il1racp", "il1racp enabling", "enabling the formation", "the formation of", "formation of a", "of a high", "a high affinity", "high affinity ligand", "affinity ligand receptor", "ligand receptor complex", "receptor complex that", "complex that is", "that is capable", "is capable of", "capable of signal", "of signal transduction.", "signal transduction. intracellular", "transduction. intracellular signaling", "intracellular signaling is", "signaling is initiated", "is initiated by", "initiated by the", "by the recruitment", "recruitment of myd88", "of myd88 to", "myd88 to the", "to the il", "the il 1r1/il1rap", "il 1r1/il1rap complex.", "1r1/il1rap complex. il1rap", "complex. il1rap is", "il1rap is only", "is only recruited", "only recruited to", "recruited to il1r1", "to il1r1 when", "il1r1 when il1", "when il1 is", "il1 is present", "present it", "it is believed", "is believed that", "believed that a", "that a tir", "a tir domain", "tir domain signaling", "domain signaling complex", "signaling complex is", "complex is formed", "is formed between", "formed between the", "between the receptor", "the receptor and", "receptor and the", "and the adapter", "the adapter tir", "adapter tir domains.", "tir domains. the", "domains. the recruitment", "of myd88 leads", "myd88 leads to", "recruitment of interleukin", "of interleukin 1", "1 receptor associated", "receptor associated kinase", "kinase irak", "irak 1", "and 4", "4 probably", "probably via their", "via their death", "their death domains.", "death domains. irak4", "domains. irak4 then", "irak4 then activates", "then activates irak1", "irak1 allowing", "allowing irak1 to", "irak1 to autophosphorylate.", "to autophosphorylate. both", "autophosphorylate. both irak1", "both irak1 and", "irak1 and irak4", "and irak4 then", "irak4 then dissociate", "then dissociate from", "dissociate from myd88", "myd88 brikos", "brikos et al.", "et al. 2007", "2007 which", "which remains stably", "remains stably complexed", "stably complexed with", "complexed with il", "with il 1r1", "il 1r1 and", "1r1 and il1rap.", "and il1rap. they", "il1rap. they in", "they in turn", "in turn interact", "turn interact with", "interact with tumor", "with tumor necrosis", "tumor necrosis factor", "necrosis factor receptor", "receptor tnfr", "tnfr associated", "associated factor 6", "6 traf6", "which is an", "is an e3", "an e3 ubiquitin", "e3 ubiquitin ligase", "ligase deng", "deng et al.", "2000 . traf6", ". traf6 is", "traf6 is then", "is then thought", "then thought to", "thought to auto", "to auto ubiquinate", "ubiquinate attaching", "attaching k63 polyubiquitin", "k63 polyubiquitin to", "polyubiquitin to itself", "to itself with", "itself with the", "with the assistance", "the assistance of", "assistance of the", "of the e2", "the e2 conjugating", "e2 conjugating complex", "conjugating complex ubc13/uev1a.", "complex ubc13/uev1a. k63", "ubc13/uev1a. k63 pub", "k63 pub traf6", "pub traf6 recruits", "traf6 recruits transforming", "recruits transforming growth", "transforming growth factor", "factor tgf", "tgf beta", "beta activated protein", "activated protein kinase", "protein kinase 1", "1 tak1", "tak1 in", "in a complex", "a complex with", "complex with tak1", "with tak1 binding", "tak1 binding protein", "binding protein 2", "2 tab2", "tab2 and", "tab3 which", "which both contain", "both contain nuclear", "contain nuclear zinc", "nuclear zinc finger", "zinc finger motifs", "finger motifs that", "motifs that interact", "that interact with", "interact with k63", "with k63 polyubiquitin", "k63 polyubiquitin chains", "chains ninomiya", "ninomiya tsuji et", "tsuji et al.", "et al. 1999", "al. 1999 .", "1999 . this", ". this activates", "this activates tak1", "tak1 which", "which then activates", "activates inhibitor", "inhibitor of nf", "of nf kappab", "kappab ikappab", "ikappab kinase", "2 ikk2", "ikk2 or ikkb", "ikkb within", "within the ikk", "the ikk complex", "complex the", "the kinase responsible", "kinase responsible for", "responsible for phosphorylation", "for phosphorylation of", "phosphorylation of ikappab.", "of ikappab. the", "ikappab. the ikk", "ikk complex also", "complex also contains", "also contains the", "contains the scaffold", "the scaffold protein", "scaffold protein nf", "protein nf kappa", "nf kappa b", "kappa b essential", "b essential modulator", "modulator nemo", "nemo . tak1", ". tak1 also", "tak1 also couples", "also couples to", "couples to the", "to the upstream", "the upstream kinases", "upstream kinases for", "kinases for p38", "for p38 and", "p38 and c", "and c jun", "c jun n", "jun n terminal", "n terminal kinase", "kinase jnk", "jnk . irak1", ". irak1 undergoes", "irak1 undergoes k63", "undergoes k63 linked", "k63 linked polyubiquination", "polyubiquination pellino", "pellino e3 ligases", "e3 ligases are", "ligases are important", "are important in", "important in this", "in this process.", "process. butler", "butler et al.", "2007 ordureau", "ordureau et al.", "et al. 2008", "al. 2008 .", "2008 . the", ". the activity", "the activity of", "activity of these", "of these proteins", "these proteins is", "proteins is greatly", "is greatly enhanced", "greatly enhanced by", "enhanced by irak", "by irak phosphorylation", "phosphorylation schauvliege", "schauvliege et al.", "et al. 2006", "leading to k63", "to k63 linked", "k63 linked polyubiquitination", "linked polyubiquitination of", "polyubiquitination of irak1.", "of irak1. this", "irak1. this recruits", "this recruits nemo", "recruits nemo to", "nemo to irak1", "irak1 with", "with nemo binding", "nemo binding to", "binding to polyubiquitin", "polyubiquitin conze", "conze et al.", "al. 2008 .

tak1", "2008 .

tak1 activates", ".

tak1 activates ikkb", "ikkb and", "resulting in phosphorylation", "in phosphorylation of", "phosphorylation of the", "of the inhibitory", "the inhibitory ikb", "inhibitory ikb proteins", "ikb proteins and", "proteins and enabling", "and enabling translocation", "enabling translocation of", "translocation of nfkb", "of nfkb to", "nfkb to the", "to the nucleus", "nucleus ikkb", "ikkb also phosphorylates", "also phosphorylates nfkb", "phosphorylates nfkb p105", "p105 leading", "leading to its", "to its degradation", "its degradation and", "degradation and the", "and the subsequent", "the subsequent release", "subsequent release of", "release of active", "of active tpl2", "active tpl2 that", "tpl2 that triggers", "that triggers the", "triggers the extracellular", "the extracellular signal", "extracellular signal regulated", "signal regulated kinase", "kinase erk", "erk 1/2 mapk", "1/2 mapk cascade.", "mapk cascade. tak1", "cascade. tak1 can", "tak1 can also", "can also trigger", "also trigger the", "trigger the p38", "the p38 and", "p38 and jnk", "and jnk mapk", "jnk mapk pathways", "mapk pathways via", "pathways via activating", "via activating the", "activating the upstream", "the upstream mkks3", "mkks3 4", "4 and 6.", "and 6. the", "6. the mapk", "the mapk pathways", "mapk pathways activate", "pathways activate a", "activate a number", "a number of", "number of downstream", "of downstream kinases", "downstream kinases and", "kinases and transcription", "and transcription factors", "transcription factors that", "factors that co", "that co operate", "co operate with", "operate with nfkb", "with nfkb to", "nfkb to induce", "to induce the", "induce the expression", "the expression of", "expression of a", "of a range", "a range of", "range of tlr/il", "of tlr/il 1r", "tlr/il 1r responsive", "1r responsive genes.", "responsive genes. there", "genes. there are", "there are reports", "are reports suggesting", "reports suggesting that", "suggesting that il1", "that il1 stimulation", "il1 stimulation increases", "stimulation increases nuclear", "increases nuclear localization", "nuclear localization of", "localization of irak1", "irak1 bol", "bol et al.", "2000 and", "and that nuclear", "that nuclear irak1", "nuclear irak1 binds", "irak1 binds to", "binds to the", "to the promoter", "the promoter of", "promoter of nfkb", "of nfkb regulated", "nfkb regulated gene", "regulated gene and", "gene and ikba", "ikba enhancing", "enhancing binding of", "binding of the", "of the nfkb", "the nfkb p65", "nfkb p65 subunit", "p65 subunit to", "subunit to nfkb", "to nfkb responsive", "nfkb responsive elements", "responsive elements within", "elements within the", "within the ikba", "the ikba promoter.", "promoter. irak1", "irak1 is required", "is required for", "required for il1", "for il1 induced", "il1 induced ser", "induced ser 10", "ser 10 phosphorylation", "10 phosphorylation of", "phosphorylation of histone", "of histone h3", "histone h3 in", "h3 in vivo", "vivo liu", "liu et al.", "2008 . however", "however details", "details of this", "of this aspect", "this aspect of", "aspect of irak1", "of irak1 signaling", "irak1 signaling mechanisms", "signaling mechanisms remain", "mechanisms remain unclear.", "remain unclear. interleukin", "unclear. interleukin 18", "interleukin 18 is", "18 is another", "is another interleukin", "another interleukin 1", "interleukin 1 related", "1 related cytokine", "related cytokine which", "cytokine which signals", "which signals through", "signals through il18r", "through il18r and", "il18r and il18rap", "and il18rap subunit", "il18rap subunit receptors", "receptors which", "which share homology", "share homology with", "homology with il1r", "with il1r and", "il1r and il1rap", "and il1rap in", "il1rap in the", "in the cytokine", "the cytokine signaling", "cytokine signaling cascade", "signaling cascade .", "cascade . later", ". later it", "later it follows", "it follows a", "follows a myd88/irak1/traf6", "a myd88/irak1/traf6 cascade", "myd88/irak1/traf6 cascade signaling", "cascade signaling until", "signaling until reach", "until reach the", "reach the nfkb", "the nfkb activation", "activation moller", "moller et al.", "et al. 2002", "al. 2002 .", "2002 . interleukin", ". interleukin 33", "33 36", "36 37", "37 and 38", "and 38 are", "38 are relatively", "are relatively recently", "relatively recently discovered", "recently discovered interleukin", "discovered interleukin 1", "1 related citokines", "related citokines which", "citokines which are", "which are also", "are also able", "also able to", "able to signal", "to signal through", "signal through il1", "through il1 receptor", "il1 receptor subunits", "receptor subunits or", "subunits or other", "or other as", "other as il18r", "il18r il37r", "il37r schmitz", "schmitz et al.", "et al. 2005", "2005 yi", "yi et al.", "et al. 2016", "2016 lunding", "lunding et al.", "et al. 2015", "2015 van", "van de veendorck", "de veendorck et", "veendorck et al.", "et al. 2012", "2012 lin", "lin et al.", "et al. 2001", "al. 2001 .", "interleukin 1 il1", "il1 signals via", "signals via interleukin 1", "via interleukin 1 receptor", "interleukin 1 receptor 1", "receptor 1 il1r1", "il1r1 the", "the only signaling capable", "only signaling capable il1", "signaling capable il1 receptor.", "capable il1 receptor. this", "il1 receptor. this is", "receptor. this is a", "this is a single", "is a single chain", "a single chain type", "single chain type 1", "chain type 1 transmembrane", "type 1 transmembrane protein", "1 transmembrane protein comprising", "transmembrane protein comprising an", "protein comprising an extracellular", "comprising an extracellular ligand", "an extracellular ligand binding", "extracellular ligand binding domain", "ligand binding domain and", "binding domain and an", "domain and an intracellular", "an intracellular region", "intracellular region called", "region called the toll/interleukin", "called the toll/interleukin 1", "the toll/interleukin 1 receptor", "1 receptor tir", "tir domain that", "domain that is structurally", "that is structurally conserved", "is structurally conserved and", "structurally conserved and shared", "conserved and shared by", "and shared by other", "shared by other members", "by other members of", "other members of the", "members of the two", "of the two families", "the two families of", "two families of receptors", "of receptors xu", "receptors xu et", "xu et al. 2000", "et al. 2000 .", "al. 2000 . this", "2000 . this domain", ". this domain is", "this domain is also", "domain is also shared", "is also shared by", "also shared by the", "shared by the downstream", "by the downstream adapter", "the downstream adapter molecule", "downstream adapter molecule myd88.", "adapter molecule myd88. il1", "molecule myd88. il1 binding", "myd88. il1 binding to", "il1 binding to il1r1", "binding to il1r1 leads", "to il1r1 leads to", "il1r1 leads to the", "leads to the recruitment", "to the recruitment of", "the recruitment of a", "recruitment of a second", "of a second receptor", "a second receptor chain", "second receptor chain termed", "receptor chain termed the", "chain termed the il1", "termed the il1 receptor", "the il1 receptor accessory", "il1 receptor accessory protein", "accessory protein il1rap", "protein il1rap or", "or il1racp enabling", "il1racp enabling the", "enabling the formation of", "the formation of a", "formation of a high", "of a high affinity", "a high affinity ligand", "high affinity ligand receptor", "affinity ligand receptor complex", "ligand receptor complex that", "receptor complex that is", "complex that is capable", "that is capable of", "is capable of signal", "capable of signal transduction.", "of signal transduction. intracellular", "signal transduction. intracellular signaling", "transduction. intracellular signaling is", "intracellular signaling is initiated", "signaling is initiated by", "is initiated by the", "initiated by the recruitment", "by the recruitment of", "the recruitment of myd88", "recruitment of myd88 to", "of myd88 to the", "myd88 to the il", "to the il 1r1/il1rap", "the il 1r1/il1rap complex.", "il 1r1/il1rap complex. il1rap", "1r1/il1rap complex. il1rap is", "complex. il1rap is only", "il1rap is only recruited", "is only recruited to", "only recruited to il1r1", "recruited to il1r1 when", "to il1r1 when il1", "il1r1 when il1 is", "when il1 is present", "is present it", "present it is", "it is believed that", "is believed that a", "believed that a tir", "that a tir domain", "a tir domain signaling", "tir domain signaling complex", "domain signaling complex is", "signaling complex is formed", "complex is formed between", "is formed between the", "formed between the receptor", "between the receptor and", "the receptor and the", "receptor and the adapter", "and the adapter tir", "the adapter tir domains.", "adapter tir domains. the", "tir domains. the recruitment", "domains. the recruitment of", "recruitment of myd88 leads", "of myd88 leads to", "myd88 leads to the", "the recruitment of interleukin", "recruitment of interleukin 1", "of interleukin 1 receptor", "interleukin 1 receptor associated", "1 receptor associated kinase", "associated kinase irak", "irak 1 and", "1 and 4", "4 probably via", "probably via their death", "via their death domains.", "their death domains. irak4", "death domains. irak4 then", "domains. irak4 then activates", "irak4 then activates irak1", "activates irak1 allowing", "irak1 allowing irak1", "allowing irak1 to autophosphorylate.", "irak1 to autophosphorylate. both", "to autophosphorylate. both irak1", "autophosphorylate. both irak1 and", "both irak1 and irak4", "irak1 and irak4 then", "and irak4 then dissociate", "irak4 then dissociate from", "then dissociate from myd88", "from myd88 brikos", "myd88 brikos et", "brikos et al. 2007", "al. 2007 which", "2007 which remains", "which remains stably complexed", "remains stably complexed with", "stably complexed with il", "complexed with il 1r1", "with il 1r1 and", "il 1r1 and il1rap.", "1r1 and il1rap. they", "and il1rap. they in", "il1rap. they in turn", "they in turn interact", "in turn interact with", "turn interact with tumor", "interact with tumor necrosis", "with tumor necrosis factor", "tumor necrosis factor receptor", "factor receptor tnfr", "tnfr associated factor", "factor 6 traf6", "traf6 which", "which is an e3", "is an e3 ubiquitin", "an e3 ubiquitin ligase", "ubiquitin ligase deng", "ligase deng et", "deng et al. 2000", "al. 2000 . traf6", "2000 . traf6 is", ". traf6 is then", "traf6 is then thought", "is then thought to", "then thought to auto", "thought to auto ubiquinate", "auto ubiquinate attaching", "ubiquinate attaching k63", "attaching k63 polyubiquitin to", "k63 polyubiquitin to itself", "polyubiquitin to itself with", "to itself with the", "itself with the assistance", "with the assistance of", "the assistance of the", "assistance of the e2", "of the e2 conjugating", "the e2 conjugating complex", "e2 conjugating complex ubc13/uev1a.", "conjugating complex ubc13/uev1a. k63", "complex ubc13/uev1a. k63 pub", "ubc13/uev1a. k63 pub traf6", "k63 pub traf6 recruits", "pub traf6 recruits transforming", "traf6 recruits transforming growth", "recruits transforming growth factor", "growth factor tgf", "tgf beta activated", "beta activated protein kinase", "activated protein kinase 1", "kinase 1 tak1", "tak1 in a", "in a complex with", "a complex with tak1", "complex with tak1 binding", "with tak1 binding protein", "tak1 binding protein 2", "protein 2 tab2", "tab2 and tab3", "and tab3 which", "tab3 which both", "which both contain nuclear", "both contain nuclear zinc", "contain nuclear zinc finger", "nuclear zinc finger motifs", "zinc finger motifs that", "finger motifs that interact", "motifs that interact with", "that interact with k63", "interact with k63 polyubiquitin", "with k63 polyubiquitin chains", "polyubiquitin chains ninomiya", "chains ninomiya tsuji", "ninomiya tsuji et al.", "tsuji et al. 1999", "et al. 1999 .", "al. 1999 . this", "1999 . this activates", ". this activates tak1", "activates tak1 which", "tak1 which then", "then activates inhibitor", "activates inhibitor of", "inhibitor of nf kappab", "nf kappab ikappab", "ikappab kinase 2", "kinase 2 ikk2", "2 ikk2 or", "or ikkb within", "ikkb within the", "within the ikk complex", "ikk complex the", "complex the kinase", "the kinase responsible for", "kinase responsible for phosphorylation", "responsible for phosphorylation of", "for phosphorylation of ikappab.", "phosphorylation of ikappab. the", "of ikappab. the ikk", "ikappab. the ikk complex", "the ikk complex also", "ikk complex also contains", "complex also contains the", "also contains the scaffold", "contains the scaffold protein", "the scaffold protein nf", "scaffold protein nf kappa", "protein nf kappa b", "nf kappa b essential", "kappa b essential modulator", "essential modulator nemo", "modulator nemo .", "nemo . tak1 also", ". tak1 also couples", "tak1 also couples to", "also couples to the", "couples to the upstream", "to the upstream kinases", "the upstream kinases for", "upstream kinases for p38", "kinases for p38 and", "for p38 and c", "p38 and c jun", "and c jun n", "c jun n terminal", "jun n terminal kinase", "terminal kinase jnk", "kinase jnk .", "jnk . irak1 undergoes", ". irak1 undergoes k63", "irak1 undergoes k63 linked", "undergoes k63 linked polyubiquination", "linked polyubiquination pellino", "polyubiquination pellino e3", "pellino e3 ligases are", "e3 ligases are important", "ligases are important in", "are important in this", "important in this process.", "this process. butler", "process. butler et", "butler et al. 2007", "al. 2007 ordureau", "2007 ordureau et", "ordureau et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the activity", ". the activity of", "the activity of these", "activity of these proteins", "of these proteins is", "these proteins is greatly", "proteins is greatly enhanced", "is greatly enhanced by", "greatly enhanced by irak", "enhanced by irak phosphorylation", "irak phosphorylation schauvliege", "phosphorylation schauvliege et", "schauvliege et al. 2006", "2006 leading", "leading to k63 linked", "to k63 linked polyubiquitination", "k63 linked polyubiquitination of", "linked polyubiquitination of irak1.", "polyubiquitination of irak1. this", "of irak1. this recruits", "irak1. this recruits nemo", "this recruits nemo to", "recruits nemo to irak1", "to irak1 with", "irak1 with nemo", "with nemo binding to", "nemo binding to polyubiquitin", "to polyubiquitin conze", "polyubiquitin conze et", "conze et al. 2008", "et al. 2008 .

tak1", "al. 2008 .

tak1 activates", "2008 .

tak1 activates ikkb", "activates ikkb and", "ikkb and ikk", "ikk resulting", "resulting in phosphorylation of", "in phosphorylation of the", "phosphorylation of the inhibitory", "of the inhibitory ikb", "the inhibitory ikb proteins", "inhibitory ikb proteins and", "ikb proteins and enabling", "proteins and enabling translocation", "and enabling translocation of", "enabling translocation of nfkb", "translocation of nfkb to", "of nfkb to the", "nfkb to the nucleus", "the nucleus ikkb", "nucleus ikkb also", "ikkb also phosphorylates nfkb", "also phosphorylates nfkb p105", "nfkb p105 leading", "p105 leading to", "leading to its degradation", "to its degradation and", "its degradation and the", "degradation and the subsequent", "and the subsequent release", "the subsequent release of", "subsequent release of active", "release of active tpl2", "of active tpl2 that", "active tpl2 that triggers", "tpl2 that triggers the", "that triggers the extracellular", "triggers the extracellular signal", "the extracellular signal regulated", "extracellular signal regulated kinase", "regulated kinase erk", "kinase erk 1/2", "erk 1/2 mapk cascade.", "1/2 mapk cascade. tak1", "mapk cascade. tak1 can", "cascade. tak1 can also", "tak1 can also trigger", "can also trigger the", "also trigger the p38", "trigger the p38 and", "the p38 and jnk", "p38 and jnk mapk", "and jnk mapk pathways", "jnk mapk pathways via", "mapk pathways via activating", "pathways via activating the", "via activating the upstream", "activating the upstream mkks3", "upstream mkks3 4", "mkks3 4 and", "4 and 6. the", "and 6. the mapk", "6. the mapk pathways", "the mapk pathways activate", "mapk pathways activate a", "pathways activate a number", "activate a number of", "a number of downstream", "number of downstream kinases", "of downstream kinases and", "downstream kinases and transcription", "kinases and transcription factors", "and transcription factors that", "transcription factors that co", "factors that co operate", "that co operate with", "co operate with nfkb", "operate with nfkb to", "with nfkb to induce", "nfkb to induce the", "to induce the expression", "induce the expression of", "the expression of a", "expression of a range", "of a range of", "a range of tlr/il", "range of tlr/il 1r", "of tlr/il 1r responsive", "tlr/il 1r responsive genes.", "1r responsive genes. there", "responsive genes. there are", "genes. there are reports", "there are reports suggesting", "are reports suggesting that", "reports suggesting that il1", "suggesting that il1 stimulation", "that il1 stimulation increases", "il1 stimulation increases nuclear", "stimulation increases nuclear localization", "increases nuclear localization of", "nuclear localization of irak1", "of irak1 bol", "irak1 bol et", "bol et al. 2000", "al. 2000 and", "2000 and that", "and that nuclear irak1", "that nuclear irak1 binds", "nuclear irak1 binds to", "irak1 binds to the", "binds to the promoter", "to the promoter of", "the promoter of nfkb", "promoter of nfkb regulated", "of nfkb regulated gene", "nfkb regulated gene and", "regulated gene and ikba", "and ikba enhancing", "ikba enhancing binding", "enhancing binding of the", "binding of the nfkb", "of the nfkb p65", "the nfkb p65 subunit", "nfkb p65 subunit to", "p65 subunit to nfkb", "subunit to nfkb responsive", "to nfkb responsive elements", "nfkb responsive elements within", "responsive elements within the", "elements within the ikba", "within the ikba promoter.", "ikba promoter. irak1", "promoter. irak1 is", "irak1 is required for", "is required for il1", "required for il1 induced", "for il1 induced ser", "il1 induced ser 10", "induced ser 10 phosphorylation", "ser 10 phosphorylation of", "10 phosphorylation of histone", "phosphorylation of histone h3", "of histone h3 in", "histone h3 in vivo", "in vivo liu", "vivo liu et", "liu et al. 2008", "al. 2008 . however", ". however details", "however details of", "details of this aspect", "of this aspect of", "this aspect of irak1", "aspect of irak1 signaling", "of irak1 signaling mechanisms", "irak1 signaling mechanisms remain", "signaling mechanisms remain unclear.", "mechanisms remain unclear. interleukin", "remain unclear. interleukin 18", "unclear. interleukin 18 is", "interleukin 18 is another", "18 is another interleukin", "is another interleukin 1", "another interleukin 1 related", "interleukin 1 related cytokine", "1 related cytokine which", "related cytokine which signals", "cytokine which signals through", "which signals through il18r", "signals through il18r and", "through il18r and il18rap", "il18r and il18rap subunit", "and il18rap subunit receptors", "subunit receptors which", "receptors which share", "which share homology with", "share homology with il1r", "homology with il1r and", "with il1r and il1rap", "il1r and il1rap in", "and il1rap in the", "il1rap in the cytokine", "in the cytokine signaling", "the cytokine signaling cascade", "cytokine signaling cascade .", "signaling cascade . later", "cascade . later it", ". later it follows", "later it follows a", "it follows a myd88/irak1/traf6", "follows a myd88/irak1/traf6 cascade", "a myd88/irak1/traf6 cascade signaling", "myd88/irak1/traf6 cascade signaling until", "cascade signaling until reach", "signaling until reach the", "until reach the nfkb", "reach the nfkb activation", "nfkb activation moller", "activation moller et", "moller et al. 2002", "et al. 2002 .", "al. 2002 . interleukin", "2002 . interleukin 33", "interleukin 33 36", "36 37 and", "37 and 38 are", "and 38 are relatively", "38 are relatively recently", "are relatively recently discovered", "relatively recently discovered interleukin", "recently discovered interleukin 1", "discovered interleukin 1 related", "interleukin 1 related citokines", "1 related citokines which", "related citokines which are", "citokines which are also", "which are also able", "are also able to", "also able to signal", "able to signal through", "to signal through il1", "signal through il1 receptor", "through il1 receptor subunits", "il1 receptor subunits or", "receptor subunits or other", "subunits or other as", "or other as il18r", "as il18r il37r", "il37r schmitz et", "schmitz et al. 2005", "al. 2005 yi", "2005 yi et", "yi et al. 2016", "al. 2016 lunding", "2016 lunding et", "lunding et al. 2015", "al. 2015 van", "2015 van de", "van de veendorck et", "de veendorck et al.", "veendorck et al. 2012", "al. 2012 lin", "2012 lin et", "lin et al. 2001", "et al. 2001 .", "1 il1 signals", "il1 signals via interleukin", "signals via interleukin 1 receptor", "via interleukin 1 receptor 1", "1 receptor 1 il1r1", "il1r1 the only", "the only signaling capable il1", "only signaling capable il1 receptor.", "signaling capable il1 receptor. this", "capable il1 receptor. this is", "il1 receptor. this is a", "receptor. this is a single", "this is a single chain", "is a single chain type", "a single chain type 1", "single chain type 1 transmembrane", "chain type 1 transmembrane protein", "type 1 transmembrane protein comprising", "1 transmembrane protein comprising an", "transmembrane protein comprising an extracellular", "protein comprising an extracellular ligand", "comprising an extracellular ligand binding", "an extracellular ligand binding domain", "extracellular ligand binding domain and", "ligand binding domain and an", "binding domain and an intracellular", "and an intracellular region", "an intracellular region called", "intracellular region called the", "region called the toll/interleukin 1", "called the toll/interleukin 1 receptor", "toll/interleukin 1 receptor tir", "receptor tir domain", "tir domain that is", "domain that is structurally conserved", "that is structurally conserved and", "is structurally conserved and shared", "structurally conserved and shared by", "conserved and shared by other", "and shared by other members", "shared by other members of", "by other members of the", "other members of the two", "members of the two families", "of the two families of", "the two families of receptors", "families of receptors xu", "of receptors xu et", "receptors xu et al.", "xu et al. 2000 .", "et al. 2000 . this", "al. 2000 . this domain", "2000 . this domain is", ". this domain is also", "this domain is also shared", "domain is also shared by", "is also shared by the", "also shared by the downstream", "shared by the downstream adapter", "by the downstream adapter molecule", "the downstream adapter molecule myd88.", "downstream adapter molecule myd88. il1", "adapter molecule myd88. il1 binding", "molecule myd88. il1 binding to", "myd88. il1 binding to il1r1", "il1 binding to il1r1 leads", "binding to il1r1 leads to", "to il1r1 leads to the", "il1r1 leads to the recruitment", "leads to the recruitment of", "to the recruitment of a", "the recruitment of a second", "recruitment of a second receptor", "of a second receptor chain", "a second receptor chain termed", "second receptor chain termed the", "receptor chain termed the il1", "chain termed the il1 receptor", "termed the il1 receptor accessory", "the il1 receptor accessory protein", "receptor accessory protein il1rap", "accessory protein il1rap or", "protein il1rap or il1racp", "il1rap or il1racp enabling", "or il1racp enabling the", "il1racp enabling the formation", "enabling the formation of a", "the formation of a high", "formation of a high affinity", "of a high affinity ligand", "a high affinity ligand receptor", "high affinity ligand receptor complex", "affinity ligand receptor complex that", "ligand receptor complex that is", "receptor complex that is capable", "complex that is capable of", "that is capable of signal", "is capable of signal transduction.", "capable of signal transduction. intracellular", "of signal transduction. intracellular signaling", "signal transduction. intracellular signaling is", "transduction. intracellular signaling is initiated", "intracellular signaling is initiated by", "signaling is initiated by the", "is initiated by the recruitment", "initiated by the recruitment of", "by the recruitment of myd88", "the recruitment of myd88 to", "recruitment of myd88 to the", "of myd88 to the il", "myd88 to the il 1r1/il1rap", "to the il 1r1/il1rap complex.", "the il 1r1/il1rap complex. il1rap", "il 1r1/il1rap complex. il1rap is", "1r1/il1rap complex. il1rap is only", "complex. il1rap is only recruited", "il1rap is only recruited to", "is only recruited to il1r1", "only recruited to il1r1 when", "recruited to il1r1 when il1", "to il1r1 when il1 is", "il1r1 when il1 is present", "il1 is present it", "is present it is", "present it is believed", "it is believed that a", "is believed that a tir", "believed that a tir domain", "that a tir domain signaling", "a tir domain signaling complex", "tir domain signaling complex is", "domain signaling complex is formed", "signaling complex is formed between", "complex is formed between the", "is formed between the receptor", "formed between the receptor and", "between the receptor and the", "the receptor and the adapter", "receptor and the adapter tir", "and the adapter tir domains.", "the adapter tir domains. the", "adapter tir domains. the recruitment", "tir domains. the recruitment of", "domains. the recruitment of myd88", "the recruitment of myd88 leads", "recruitment of myd88 leads to", "of myd88 leads to the", "myd88 leads to the recruitment", "to the recruitment of interleukin", "the recruitment of interleukin 1", "recruitment of interleukin 1 receptor", "of interleukin 1 receptor associated", "interleukin 1 receptor associated kinase", "receptor associated kinase irak", "kinase irak 1", "and 4 probably", "4 probably via their", "probably via their death domains.", "via their death domains. irak4", "their death domains. irak4 then", "death domains. irak4 then activates", "domains. irak4 then activates irak1", "then activates irak1 allowing", "activates irak1 allowing irak1", "irak1 allowing irak1 to", "allowing irak1 to autophosphorylate. both", "irak1 to autophosphorylate. both irak1", "to autophosphorylate. both irak1 and", "autophosphorylate. both irak1 and irak4", "both irak1 and irak4 then", "irak1 and irak4 then dissociate", "and irak4 then dissociate from", "irak4 then dissociate from myd88", "dissociate from myd88 brikos", "from myd88 brikos et", "myd88 brikos et al.", "et al. 2007 which", "al. 2007 which remains", "2007 which remains stably", "which remains stably complexed with", "remains stably complexed with il", "stably complexed with il 1r1", "complexed with il 1r1 and", "with il 1r1 and il1rap.", "il 1r1 and il1rap. they", "1r1 and il1rap. they in", "and il1rap. they in turn", "il1rap. they in turn interact", "they in turn interact with", "in turn interact with tumor", "turn interact with tumor necrosis", "interact with tumor necrosis factor", "with tumor necrosis factor receptor", "necrosis factor receptor tnfr", "receptor tnfr associated", "tnfr associated factor 6", "associated factor 6 traf6", "traf6 which is", "which is an e3 ubiquitin", "is an e3 ubiquitin ligase", "e3 ubiquitin ligase deng", "ubiquitin ligase deng et", "ligase deng et al.", "deng et al. 2000 .", "et al. 2000 . traf6", "al. 2000 . traf6 is", "2000 . traf6 is then", ". traf6 is then thought", "traf6 is then thought to", "is then thought to auto", "then thought to auto ubiquinate", "to auto ubiquinate attaching", "auto ubiquinate attaching k63", "ubiquinate attaching k63 polyubiquitin", "attaching k63 polyubiquitin to itself", "k63 polyubiquitin to itself with", "polyubiquitin to itself with the", "to itself with the assistance", "itself with the assistance of", "with the assistance of the", "the assistance of the e2", "assistance of the e2 conjugating", "of the e2 conjugating complex", "the e2 conjugating complex ubc13/uev1a.", "e2 conjugating complex ubc13/uev1a. k63", "conjugating complex ubc13/uev1a. k63 pub", "complex ubc13/uev1a. k63 pub traf6", "ubc13/uev1a. k63 pub traf6 recruits", "k63 pub traf6 recruits transforming", "pub traf6 recruits transforming growth", "traf6 recruits transforming growth factor", "transforming growth factor tgf", "factor tgf beta", "tgf beta activated protein", "beta activated protein kinase 1", "protein kinase 1 tak1", "1 tak1 in", "tak1 in a complex", "in a complex with tak1", "a complex with tak1 binding", "complex with tak1 binding protein", "with tak1 binding protein 2", "binding protein 2 tab2", "2 tab2 and", "and tab3 which both", "tab3 which both contain", "which both contain nuclear zinc", "both contain nuclear zinc finger", "contain nuclear zinc finger motifs", "nuclear zinc finger motifs that", "zinc finger motifs that interact", "finger motifs that interact with", "motifs that interact with k63", "that interact with k63 polyubiquitin", "interact with k63 polyubiquitin chains", "k63 polyubiquitin chains ninomiya", "polyubiquitin chains ninomiya tsuji", "chains ninomiya tsuji et", "ninomiya tsuji et al. 1999", "tsuji et al. 1999 .", "et al. 1999 . this", "al. 1999 . this activates", "1999 . this activates tak1", "this activates tak1 which", "activates tak1 which then", "tak1 which then activates", "which then activates inhibitor", "then activates inhibitor of", "activates inhibitor of nf", "of nf kappab ikappab", "kappab ikappab kinase", "kinase 2 ikk2 or", "2 ikk2 or ikkb", "ikk2 or ikkb within", "or ikkb within the", "ikkb within the ikk", "the ikk complex the", "ikk complex the kinase", "complex the kinase responsible", "the kinase responsible for phosphorylation", "kinase responsible for phosphorylation of", "responsible for phosphorylation of ikappab.", "for phosphorylation of ikappab. the", "phosphorylation of ikappab. the ikk", "of ikappab. the ikk complex", "ikappab. the ikk complex also", "the ikk complex also contains", "ikk complex also contains the", "complex also contains the scaffold", "also contains the scaffold protein", "contains the scaffold protein nf", "the scaffold protein nf kappa", "scaffold protein nf kappa b", "protein nf kappa b essential", "nf kappa b essential modulator", "b essential modulator nemo", "essential modulator nemo .", "modulator nemo . tak1", "nemo . tak1 also couples", ". tak1 also couples to", "tak1 also couples to the", "also couples to the upstream", "couples to the upstream kinases", "to the upstream kinases for", "the upstream kinases for p38", "upstream kinases for p38 and", "kinases for p38 and c", "for p38 and c jun", "p38 and c jun n", "and c jun n terminal", "c jun n terminal kinase", "n terminal kinase jnk", "terminal kinase jnk .", "kinase jnk . irak1", "jnk . irak1 undergoes k63", ". irak1 undergoes k63 linked", "irak1 undergoes k63 linked polyubiquination", "k63 linked polyubiquination pellino", "linked polyubiquination pellino e3", "polyubiquination pellino e3 ligases", "pellino e3 ligases are important", "e3 ligases are important in", "ligases are important in this", "are important in this process.", "in this process. butler", "this process. butler et", "process. butler et al.", "et al. 2007 ordureau", "al. 2007 ordureau et", "2007 ordureau et al.", "ordureau et al. 2008 .", "et al. 2008 . the", "al. 2008 . the activity", "2008 . the activity of", ". the activity of these", "the activity of these proteins", "activity of these proteins is", "of these proteins is greatly", "these proteins is greatly enhanced", "proteins is greatly enhanced by", "is greatly enhanced by irak", "greatly enhanced by irak phosphorylation", "by irak phosphorylation schauvliege", "irak phosphorylation schauvliege et", "phosphorylation schauvliege et al.", "al. 2006 leading", "2006 leading to", "leading to k63 linked polyubiquitination", "to k63 linked polyubiquitination of", "k63 linked polyubiquitination of irak1.", "linked polyubiquitination of irak1. this", "polyubiquitination of irak1. this recruits", "of irak1. this recruits nemo", "irak1. this recruits nemo to", "this recruits nemo to irak1", "nemo to irak1 with", "to irak1 with nemo", "irak1 with nemo binding", "with nemo binding to polyubiquitin", "binding to polyubiquitin conze", "to polyubiquitin conze et", "polyubiquitin conze et al.", "conze et al. 2008 .

tak1", "et al. 2008 .

tak1 activates", "al. 2008 .

tak1 activates ikkb", ".

tak1 activates ikkb and", "activates ikkb and ikk", "and ikk resulting", "ikk resulting in", "resulting in phosphorylation of the", "in phosphorylation of the inhibitory", "phosphorylation of the inhibitory ikb", "of the inhibitory ikb proteins", "the inhibitory ikb proteins and", "inhibitory ikb proteins and enabling", "ikb proteins and enabling translocation", "proteins and enabling translocation of", "and enabling translocation of nfkb", "enabling translocation of nfkb to", "translocation of nfkb to the", "of nfkb to the nucleus", "to the nucleus ikkb", "the nucleus ikkb also", "nucleus ikkb also phosphorylates", "ikkb also phosphorylates nfkb p105", "phosphorylates nfkb p105 leading", "nfkb p105 leading to", "p105 leading to its", "leading to its degradation and", "to its degradation and the", "its degradation and the subsequent", "degradation and the subsequent release", "and the subsequent release of", "the subsequent release of active", "subsequent release of active tpl2", "release of active tpl2 that", "of active tpl2 that triggers", "active tpl2 that triggers the", "tpl2 that triggers the extracellular", "that triggers the extracellular signal", "triggers the extracellular signal regulated", "the extracellular signal regulated kinase", "signal regulated kinase erk", "regulated kinase erk 1/2", "kinase erk 1/2 mapk", "erk 1/2 mapk cascade. tak1", "1/2 mapk cascade. tak1 can", "mapk cascade. tak1 can also", "cascade. tak1 can also trigger", "tak1 can also trigger the", "can also trigger the p38", "also trigger the p38 and", "trigger the p38 and jnk", "the p38 and jnk mapk", "p38 and jnk mapk pathways", "and jnk mapk pathways via", "jnk mapk pathways via activating", "mapk pathways via activating the", "pathways via activating the upstream", "via activating the upstream mkks3", "the upstream mkks3 4", "upstream mkks3 4 and", "mkks3 4 and 6.", "4 and 6. the mapk", "and 6. the mapk pathways", "6. the mapk pathways activate", "the mapk pathways activate a", "mapk pathways activate a number", "pathways activate a number of", "activate a number of downstream", "a number of downstream kinases", "number of downstream kinases and", "of downstream kinases and transcription", "downstream kinases and transcription factors", "kinases and transcription factors that", "and transcription factors that co", "transcription factors that co operate", "factors that co operate with", "that co operate with nfkb", "co operate with nfkb to", "operate with nfkb to induce", "with nfkb to induce the", "nfkb to induce the expression", "to induce the expression of", "induce the expression of a", "the expression of a range", "expression of a range of", "of a range of tlr/il", "a range of tlr/il 1r", "range of tlr/il 1r responsive", "of tlr/il 1r responsive genes.", "tlr/il 1r responsive genes. there", "1r responsive genes. there are", "responsive genes. there are reports", "genes. there are reports suggesting", "there are reports suggesting that", "are reports suggesting that il1", "reports suggesting that il1 stimulation", "suggesting that il1 stimulation increases", "that il1 stimulation increases nuclear", "il1 stimulation increases nuclear localization", "stimulation increases nuclear localization of", "increases nuclear localization of irak1", "localization of irak1 bol", "of irak1 bol et", "irak1 bol et al.", "et al. 2000 and", "al. 2000 and that", "2000 and that nuclear", "and that nuclear irak1 binds", "that nuclear irak1 binds to", "nuclear irak1 binds to the", "irak1 binds to the promoter", "binds to the promoter of", "to the promoter of nfkb", "the promoter of nfkb regulated", "promoter of nfkb regulated gene", "of nfkb regulated gene and", "nfkb regulated gene and ikba", "gene and ikba enhancing", "and ikba enhancing binding", "ikba enhancing binding of", "enhancing binding of the nfkb", "binding of the nfkb p65", "of the nfkb p65 subunit", "the nfkb p65 subunit to", "nfkb p65 subunit to nfkb", "p65 subunit to nfkb responsive", "subunit to nfkb responsive elements", "to nfkb responsive elements within", "nfkb responsive elements within the", "responsive elements within the ikba", "elements within the ikba promoter.", "the ikba promoter. irak1", "ikba promoter. irak1 is", "promoter. irak1 is required", "irak1 is required for il1", "is required for il1 induced", "required for il1 induced ser", "for il1 induced ser 10", "il1 induced ser 10 phosphorylation", "induced ser 10 phosphorylation of", "ser 10 phosphorylation of histone", "10 phosphorylation of histone h3", "phosphorylation of histone h3 in", "of histone h3 in vivo", "h3 in vivo liu", "in vivo liu et", "vivo liu et al.", "liu et al. 2008 .", "et al. 2008 . however", "2008 . however details", ". however details of", "however details of this", "details of this aspect of", "of this aspect of irak1", "this aspect of irak1 signaling", "aspect of irak1 signaling mechanisms", "of irak1 signaling mechanisms remain", "irak1 signaling mechanisms remain unclear.", "signaling mechanisms remain unclear. interleukin", "mechanisms remain unclear. interleukin 18", "remain unclear. interleukin 18 is", "unclear. interleukin 18 is another", "interleukin 18 is another interleukin", "18 is another interleukin 1", "is another interleukin 1 related", "another interleukin 1 related cytokine", "interleukin 1 related cytokine which", "1 related cytokine which signals", "related cytokine which signals through", "cytokine which signals through il18r", "which signals through il18r and", "signals through il18r and il18rap", "through il18r and il18rap subunit", "il18r and il18rap subunit receptors", "il18rap subunit receptors which", "subunit receptors which share", "receptors which share homology", "which share homology with il1r", "share homology with il1r and", "homology with il1r and il1rap", "with il1r and il1rap in", "il1r and il1rap in the", "and il1rap in the cytokine", "il1rap in the cytokine signaling", "in the cytokine signaling cascade", "the cytokine signaling cascade .", "cytokine signaling cascade . later", "signaling cascade . later it", "cascade . later it follows", ". later it follows a", "later it follows a myd88/irak1/traf6", "it follows a myd88/irak1/traf6 cascade", "follows a myd88/irak1/traf6 cascade signaling", "a myd88/irak1/traf6 cascade signaling until", "myd88/irak1/traf6 cascade signaling until reach", "cascade signaling until reach the", "signaling until reach the nfkb", "until reach the nfkb activation", "the nfkb activation moller", "nfkb activation moller et", "activation moller et al.", "moller et al. 2002 .", "et al. 2002 . interleukin", "al. 2002 . interleukin 33", ". interleukin 33 36", "33 36 37", "36 37 and 38", "37 and 38 are relatively", "and 38 are relatively recently", "38 are relatively recently discovered", "are relatively recently discovered interleukin", "relatively recently discovered interleukin 1", "recently discovered interleukin 1 related", "discovered interleukin 1 related citokines", "interleukin 1 related citokines which", "1 related citokines which are", "related citokines which are also", "citokines which are also able", "which are also able to", "are also able to signal", "also able to signal through", "able to signal through il1", "to signal through il1 receptor", "signal through il1 receptor subunits", "through il1 receptor subunits or", "il1 receptor subunits or other", "receptor subunits or other as", "subunits or other as il18r", "other as il18r il37r", "il18r il37r schmitz", "il37r schmitz et al.", "et al. 2005 yi", "al. 2005 yi et", "2005 yi et al.", "et al. 2016 lunding", "al. 2016 lunding et", "2016 lunding et al.", "et al. 2015 van", "al. 2015 van de", "2015 van de veendorck", "van de veendorck et al.", "de veendorck et al. 2012", "et al. 2012 lin", "al. 2012 lin et", "2012 lin et al.", "lin et al. 2001 ." ] }, { "record_id": "GLY_000594_1_665", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9022537", "r hsa", "hsa 9022537", "r hsa 9022537" ] }, { "record_id": "GLY_000594_1_665", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "loss of", "of mecp2", "mecp2 binding", "binding ability", "ability to", "to the", "the ncor/smrt", "ncor/smrt complex", "loss of mecp2", "of mecp2 binding", "mecp2 binding ability", "binding ability to", "ability to the", "to the ncor/smrt", "the ncor/smrt complex", "loss of mecp2 binding", "of mecp2 binding ability", "mecp2 binding ability to", "binding ability to the", "ability to the ncor/smrt", "to the ncor/smrt complex", "loss of mecp2 binding ability", "of mecp2 binding ability to", "mecp2 binding ability to the", "binding ability to the ncor/smrt", "ability to the ncor/smrt complex", "missense mutations", "mutations in", "in the", "the transcriptional", "transcriptional repression", "repression domain", "domain of", "of methyl", "methyl cpg", "cpg binding", "binding protein", "protein 2", "can negatively", 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translation", ".

translation of", "mecp2 mrna", "mrna is", "is negatively", "negatively regulated", "by the", "the microrna", "microrna mir", "mir 132.", "132. transcription", "of mir", "mir 132", "132 is", "is regulated", "by bdnf", "bdnf signaling", "through an", "an unknown", "unknown mechanism", "klein et", "al. 2007", "su et", "al. 2015", "2015 .

binding", ".

binding of", "mecp2 to", "to other", "other proteins", "proteins and", "and to", "to dna", "dna is", "by posttranslational", "posttranslational modifications", "of which", "which phosphorylation", "phosphorylation has", "has been", "been best", "best studied.", "studied. calcium", "calcium dependent", "dependent protein", "protein kinases", "pka and", "and camk", "camk iv", "activated by", "by neuronal", "neuronal membrane", "membrane depolarization", "phosphorylate mecp2", "mecp2 at", "at threonine", "threonine residue", "residue t308", "corresponding to", "to t320", "t320 in", "in the", "the longer", "longer mecp2", "mecp2 splicing", "splicing isoform", "mecp2_e1 .", ". phosphorylation", "phosphorylation at", "at t308", "t308 correlates", "correlates with", "with neuronal", "neuronal activity", "activity and", "and inhibits", "inhibits binding", "binding of", "to the", "the nuclear", "nuclear receptor", "receptor co", "co repressor", "repressor complex", "ebert et", "2013 .", ". in", "in resting", "resting neurons", "mecp2 is", "is phosphorylated", "phosphorylated at", "at serine", "serine residue", "residue s80", "which results", "results in", "in a", "a decreased", "decreased association", "association of", "mecp2 with", "with chromatin.", "chromatin. nuclear", "nuclear serine/threonine", "serine/threonine protein", "protein kinase", "kinase hipk2", "hipk2 phosphorylates", "phosphorylates mecp2", "mecp2 on", "on serine", "bracaglia et", "al. 2009", "2009 .", "in activity", "activity induced", "induced neurons", "upon neuronal", "mecp2 s80", "s80 becomes", "becomes dephosphorylated", "and mecp2", "mecp2 acquires", "acquires phosphorylation", "phosphorylation on", "serine s423", "to mouse", "mouse mecp2", "mecp2 serine", "serine s421", "s421 .", ". camk", "iv is", "is one", "one of", "the kinases", "kinases that", "that can", "can phosphorylate", "on s423.", "s423. phosphorylation", "phosphorylation of", "at s423", "s423 increases", "increases mecp2", "mecp2 binding", "binding to", "to chromatin", "zhou et", "al. 2006", "tao et", "qiu et", "al. 2012", "2012 .", ". aurkb", "aurkb phosphorylates", "residue s423", "s423 in", "in dividing", "dividing adult", "adult neuronal", "neuronal progenitor", "progenitor cells", "li et", "al. 2014", "2014 .

besides", ".

besides binding", "the ncor/smrt", "ncor/smrt co", "lyst et", "mecp2 binds", "binds the", "the sin3a", "sin3a co", "repressor complex.", "complex. this", "this interaction", "interaction involves", "involves the", "the transcriptional", "transcriptional repressor", "repressor domain", "domain of", "mecp2 and", "the amino", "amino terminal", "terminal part", "part of", "the hdac", "hdac interaction", "interaction domain", "of sin3a.", "sin3a. hdac1", "hdac1 and", "and hdac2", "hdac2 are", "are part", "complex that", "that co", "co immunoprecipitates", "immunoprecipitates with", "with mecp2", "nan et", "al. 1998", "1998 .", ". while", "while binding", "to sin3a", "sin3a at", "at target", "target genes", "genes is", "is associated", "associated with", "with transcriptional", "transcriptional repression", "to creb1", "creb1 at", "transcriptional activation", "chahrour et", "chen et", ". function", "function of", "mecp2 can", "can be", "be affected", "affected by", "by binding", "to foxg1", "another gene", "gene mutated", "mutated in", "in rett", "rett syndrome", "syndrome besides", "besides mecp2", "and cdkl5", "dastidar et", "and htt", "mcfarland et", ". the", "the subnuclear", "subnuclear localization", "localization of", "mecp2 may", "may be", "the lamin", "lamin b", "b receptor", "guarda et", "transcription of the", "of the mecp2", "the mecp2 gene", "mecp2 gene is", "gene is known", "is known to", "known to be", "to be regulated", "be regulated by", "regulated by methylation", "by methylation of", "methylation of the", "of the promoter", "the promoter and", "promoter and the", "and the first", "the first intron", "intron but", "but the responsible", "the responsible methyltransferases", "responsible methyltransferases are", "methyltransferases are not", "are not known", "known nagarajan", "nagarajan et al.", "et al. 2008", "2008 franklin", "franklin et al.", "et al. 2010", "2010 liyanage", "liyanage et al.", "et al. 2013", "al. 2013 .

translation", "2013 .

translation of", ".

translation of mecp2", "of mecp2 mrna", "mecp2 mrna is", "mrna is negatively", "is negatively regulated", "negatively regulated by", "regulated by the", "by the microrna", "the microrna mir", "microrna mir 132.", "mir 132. transcription", "132. transcription of", "transcription of mir", "of mir 132", "mir 132 is", "132 is regulated", "is regulated by", "regulated by bdnf", "by bdnf signaling", "signaling through", "through an unknown", "an unknown mechanism", "mechanism klein", "klein et al.", "et al. 2007", "2007 su", "su et al.", "et al. 2015", "al. 2015 .

binding", "2015 .

binding of", ".

binding of mecp2", "of mecp2 to", "mecp2 to other", "to other proteins", "other proteins and", "proteins and to", "and to dna", "to dna is", "dna is regulated", "regulated by posttranslational", "by posttranslational modifications", "modifications of", "of which phosphorylation", "which phosphorylation has", "phosphorylation has been", "has been best", "been best studied.", "best studied. calcium", "studied. calcium dependent", "calcium dependent protein", "dependent protein kinases", "kinases pka", "pka and camk", "and camk iv", "iv activated", "activated by neuronal", "by neuronal membrane", "neuronal membrane depolarization", "depolarization phosphorylate", "phosphorylate mecp2 at", "mecp2 at threonine", "at threonine residue", "threonine residue t308", "t308 corresponding", "corresponding to t320", "to t320 in", "t320 in the", "in the longer", "the longer mecp2", "longer mecp2 splicing", "mecp2 splicing isoform", "isoform mecp2_e1", "mecp2_e1 . phosphorylation", ". phosphorylation at", "phosphorylation at t308", "at t308 correlates", "t308 correlates with", "correlates with neuronal", "with neuronal activity", "neuronal activity and", "activity and inhibits", "and inhibits binding", "inhibits binding of", "binding of mecp2", "mecp2 to the", "to the nuclear", "the nuclear receptor", "nuclear receptor co", "receptor co repressor", "co repressor complex", "complex ncor/smrt", "ebert et al.", "al. 2013 .", "2013 . in", ". in resting", "in resting neurons", "neurons mecp2", "mecp2 is phosphorylated", "is phosphorylated at", "phosphorylated at serine", "at serine residue", "serine residue s80", "s80 which", "which results in", "results in a", "in a decreased", "a decreased association", "decreased association of", "association of mecp2", "of mecp2 with", "mecp2 with chromatin.", "with chromatin. nuclear", "chromatin. nuclear serine/threonine", "nuclear serine/threonine protein", "serine/threonine protein kinase", "protein kinase hipk2", "kinase hipk2 phosphorylates", "hipk2 phosphorylates mecp2", "phosphorylates mecp2 on", "mecp2 on serine", "on serine residue", "s80 bracaglia", "bracaglia et al.", "et al. 2009", "al. 2009 .", "2009 . in", ". in activity", "in activity induced", "activity induced neurons", "neurons upon", "upon neuronal membrane", "depolarization mecp2", "mecp2 s80 becomes", "s80 becomes dephosphorylated", "dephosphorylated and", "and mecp2 acquires", "mecp2 acquires phosphorylation", "acquires phosphorylation on", "phosphorylation on serine", "on serine s423", "s423 corresponding", "corresponding to mouse", "to mouse mecp2", "mouse mecp2 serine", "mecp2 serine s421", "serine s421 .", "s421 . camk", ". camk iv", "camk iv is", "iv is one", "is one of", "one of the", "of the kinases", "the kinases that", "kinases that can", "that can phosphorylate", "can phosphorylate mecp2", "phosphorylate mecp2 on", "mecp2 on s423.", "on s423. phosphorylation", "s423. phosphorylation of", "phosphorylation of mecp2", "of mecp2 at", "mecp2 at s423", "at s423 increases", "s423 increases mecp2", "increases mecp2 binding", "mecp2 binding to", "binding to chromatin", "chromatin zhou", "zhou et al.", "et al. 2006", "2006 tao", "tao et al.", "2009 qiu", "qiu et al.", "et al. 2012", "al. 2012 .", "2012 . aurkb", ". aurkb phosphorylates", "aurkb phosphorylates mecp2", "phosphorylates mecp2 at", "mecp2 at serine", "serine residue s423", "residue s423 in", "s423 in dividing", "in dividing adult", "dividing adult neuronal", "adult neuronal progenitor", "neuronal progenitor cells", "cells li", "li et al.", "et al. 2014", "al. 2014 .

besides", "2014 .

besides binding", ".

besides binding to", "binding to the", "to the ncor/smrt", "the ncor/smrt co", "ncor/smrt co repressor", "complex lyst", "lyst et al.", "2013 ebert", "mecp2 binds the", "binds the sin3a", "the sin3a co", "sin3a co repressor", "co repressor complex.", "repressor complex. this", "complex. this interaction", "this interaction involves", "interaction involves the", "involves the transcriptional", "the transcriptional repressor", "transcriptional repressor domain", "repressor domain of", "domain of mecp2", "of mecp2 and", "mecp2 and the", "and the amino", "the amino terminal", "amino terminal part", "terminal part of", "part of the", "of the hdac", "the hdac interaction", "hdac interaction domain", "domain hid", "hid of", "of sin3a. hdac1", "sin3a. hdac1 and", "hdac1 and hdac2", "and hdac2 are", "hdac2 are part", "are part of", "of the sin3a", "repressor complex that", "complex that co", "that co immunoprecipitates", "co immunoprecipitates with", "immunoprecipitates with mecp2", "mecp2 nan", "nan et al.", "et al. 1998", "al. 1998 .", "1998 . while", ". while binding", "while binding of", "mecp2 to sin3a", "to sin3a at", "sin3a at target", "at target genes", "target genes is", "genes is associated", "is associated with", "associated with transcriptional", "with transcriptional repression", "repression binding", "binding to creb1", "to creb1 at", "creb1 at target", "with transcriptional activation", "activation chahrour", "chahrour et al.", "2008 chen", "chen et al.", "2013 . function", ". function of", "function of mecp2", "of mecp2 can", "mecp2 can be", "can be affected", "be affected by", "affected by binding", "by binding to", "binding to foxg1", "foxg1 another", "another gene mutated", "gene mutated in", "mutated in rett", "in rett syndrome", "rett syndrome besides", "syndrome besides mecp2", "besides mecp2 and", "mecp2 and cdkl5", "cdkl5 dastidar", "dastidar et al.", "htt huntingtin", "mcfarland et al.", "2013 . the", ". the subnuclear", "the subnuclear localization", "subnuclear localization of", "localization of mecp2", "of mecp2 may", "mecp2 may be", "may be affected", "to the lamin", "the lamin b", "lamin b receptor", "receptor lbr", "guarda et al.", "transcription of the mecp2", "of the mecp2 gene", "the mecp2 gene is", "mecp2 gene is known", "gene is known to", "is known to be", "known to be regulated", "to be regulated by", "be regulated by methylation", "regulated by methylation of", "by methylation of the", "methylation of the promoter", "of the promoter and", "the promoter and the", "promoter and the first", "and the first intron", "first intron but", "intron but the", "but the responsible methyltransferases", "the responsible methyltransferases are", "responsible methyltransferases are not", "methyltransferases are not known", "not known nagarajan", "known nagarajan et", "nagarajan et al. 2008", "al. 2008 franklin", "2008 franklin et", "franklin et al. 2010", "al. 2010 liyanage", "2010 liyanage et", "liyanage et al. 2013", "et al. 2013 .

translation", "al. 2013 .

translation of", "2013 .

translation of mecp2", ".

translation of mecp2 mrna", "of mecp2 mrna is", "mecp2 mrna is negatively", "mrna is negatively regulated", "is negatively regulated by", "negatively regulated by the", "regulated by the microrna", "by the microrna mir", "the microrna mir 132.", "microrna mir 132. transcription", "mir 132. transcription of", "132. transcription of mir", "transcription of mir 132", "of mir 132 is", "mir 132 is regulated", "132 is regulated by", "is regulated by bdnf", "regulated by bdnf signaling", "bdnf signaling through", "signaling through an", "through an unknown mechanism", "unknown mechanism klein", "mechanism klein et", "klein et al. 2007", "al. 2007 su", "2007 su et", "su et al. 2015", "et al. 2015 .

binding", "al. 2015 .

binding of", "2015 .

binding of mecp2", ".

binding of mecp2 to", "of mecp2 to other", "mecp2 to other proteins", "to other proteins and", "other proteins and to", "proteins and to dna", "and to dna is", "to dna is regulated", "dna is regulated by", "is regulated by posttranslational", "regulated by posttranslational modifications", "posttranslational modifications of", "modifications of which", "of which phosphorylation has", "which phosphorylation has been", "phosphorylation has been best", "has been best studied.", "been best studied. calcium", "best studied. calcium dependent", "studied. calcium dependent protein", "calcium dependent protein kinases", "protein kinases pka", "kinases pka and", "pka and camk iv", "camk iv activated", "iv activated by", "activated by neuronal membrane", "by neuronal membrane depolarization", "membrane depolarization phosphorylate", "depolarization phosphorylate mecp2", "phosphorylate mecp2 at threonine", "mecp2 at threonine residue", "at threonine residue t308", "residue t308 corresponding", "t308 corresponding to", "corresponding to t320 in", "to t320 in the", "t320 in the longer", "in the longer mecp2", "the longer mecp2 splicing", "longer mecp2 splicing isoform", "splicing isoform mecp2_e1", "isoform mecp2_e1 .", "mecp2_e1 . phosphorylation at", ". phosphorylation at t308", "phosphorylation at t308 correlates", "at t308 correlates with", "t308 correlates with neuronal", "correlates with neuronal activity", "with neuronal activity and", "neuronal activity and inhibits", "activity and inhibits binding", "and inhibits binding of", "inhibits binding of mecp2", "binding of mecp2 to", "of mecp2 to the", "mecp2 to the nuclear", "to the nuclear receptor", "the nuclear receptor co", "nuclear receptor co repressor", "receptor co repressor complex", "repressor complex ncor/smrt", "ncor/smrt ebert", "ebert et al. 2013", "et al. 2013 .", "al. 2013 . in", "2013 . in resting", ". in resting neurons", "resting neurons mecp2", "neurons mecp2 is", "mecp2 is phosphorylated at", "is phosphorylated at serine", "phosphorylated at serine residue", "at serine residue s80", "residue s80 which", "s80 which results", "which results in a", "results in a decreased", "in a decreased association", "a decreased association of", "decreased association of mecp2", "association of mecp2 with", "of mecp2 with chromatin.", "mecp2 with chromatin. nuclear", "with chromatin. nuclear serine/threonine", "chromatin. nuclear serine/threonine protein", "nuclear serine/threonine protein kinase", "serine/threonine protein kinase hipk2", "protein kinase hipk2 phosphorylates", "kinase hipk2 phosphorylates mecp2", "hipk2 phosphorylates mecp2 on", "phosphorylates mecp2 on serine", "mecp2 on serine residue", "on serine residue s80", "residue s80 bracaglia", "s80 bracaglia et", "bracaglia et al. 2009", "et al. 2009 .", "al. 2009 . in", "2009 . in activity", ". in activity induced", "in activity induced neurons", "induced neurons upon", "neurons upon neuronal", "upon neuronal membrane depolarization", "membrane depolarization mecp2", "depolarization mecp2 s80", "mecp2 s80 becomes dephosphorylated", "becomes dephosphorylated and", "dephosphorylated and mecp2", "and mecp2 acquires phosphorylation", "mecp2 acquires phosphorylation on", "acquires phosphorylation on serine", "phosphorylation on serine s423", "serine s423 corresponding", "s423 corresponding to", "corresponding to mouse mecp2", "to mouse mecp2 serine", "mouse mecp2 serine s421", "mecp2 serine s421 .", "serine s421 . camk", "s421 . camk iv", ". camk iv is", "camk iv is one", "iv is one of", "is one of the", "one of the kinases", "of the kinases that", "the kinases that can", "kinases that can phosphorylate", "that can phosphorylate mecp2", "can phosphorylate mecp2 on", "phosphorylate mecp2 on s423.", "mecp2 on s423. phosphorylation", "on s423. phosphorylation of", "s423. phosphorylation of mecp2", "phosphorylation of mecp2 at", "of mecp2 at s423", "mecp2 at s423 increases", "at s423 increases mecp2", "s423 increases mecp2 binding", "increases mecp2 binding to", "mecp2 binding to chromatin", "to chromatin zhou", "chromatin zhou et", "zhou et al. 2006", "al. 2006 tao", "2006 tao et", "tao et al. 2009", "al. 2009 qiu", "2009 qiu et", "qiu et al. 2012", "et al. 2012 .", "al. 2012 . aurkb", "2012 . aurkb phosphorylates", ". aurkb phosphorylates mecp2", "aurkb phosphorylates mecp2 at", "phosphorylates mecp2 at serine", "mecp2 at serine residue", "at serine residue s423", "serine residue s423 in", "residue s423 in dividing", "s423 in dividing adult", "in dividing adult neuronal", "dividing adult neuronal progenitor", "adult neuronal progenitor cells", "progenitor cells li", "cells li et", "li et al. 2014", "et al. 2014 .

besides", "al. 2014 .

besides binding", "2014 .

besides binding to", ".

besides binding to the", "binding to the ncor/smrt", "to the ncor/smrt co", "the ncor/smrt co repressor", "ncor/smrt co repressor complex", "repressor complex lyst", "complex lyst et", "lyst et al. 2013", "al. 2013 ebert", "2013 ebert et", "2013 mecp2", "mecp2 binds the sin3a", "binds the sin3a co", "the sin3a co repressor", "sin3a co repressor complex.", "co repressor complex. this", "repressor complex. this interaction", "complex. this interaction involves", "this interaction involves the", "interaction involves the transcriptional", "involves the transcriptional repressor", "the transcriptional repressor domain", "transcriptional repressor domain of", "repressor domain of mecp2", "domain of mecp2 and", "of mecp2 and the", "mecp2 and the amino", "and the amino terminal", "the amino terminal part", "amino terminal part of", "terminal part of the", "part of the hdac", "of the hdac interaction", "the hdac interaction domain", "interaction domain hid", "hid of sin3a.", "of sin3a. hdac1 and", "sin3a. hdac1 and hdac2", "hdac1 and hdac2 are", "and hdac2 are part", "hdac2 are part of", "are part of the", "part of the sin3a", "of the sin3a co", "sin3a co repressor complex", "co repressor complex that", "repressor complex that co", "complex that co immunoprecipitates", "that co immunoprecipitates with", "co immunoprecipitates with mecp2", "with mecp2 nan", "mecp2 nan et", "nan et al. 1998", "et al. 1998 .", "al. 1998 . while", "1998 . while binding", ". while binding of", "while binding of mecp2", "of mecp2 to sin3a", "mecp2 to sin3a at", "to sin3a at target", "sin3a at target genes", "at target genes is", "target genes is associated", "genes is associated with", "is associated with transcriptional", "associated with transcriptional repression", "transcriptional repression binding", "repression binding to", "binding to creb1 at", "to creb1 at target", "creb1 at target genes", "associated with transcriptional activation", "transcriptional activation chahrour", "activation chahrour et", "chahrour et al. 2008", "al. 2008 chen", "2008 chen et", "chen et al. 2013", "al. 2013 . function", "2013 . function of", ". function of mecp2", "function of mecp2 can", "of mecp2 can be", "mecp2 can be affected", "can be affected by", "be affected by binding", "affected by binding to", "by binding to foxg1", "to foxg1 another", "foxg1 another gene", "another gene mutated in", "gene mutated in rett", "mutated in rett syndrome", "in rett syndrome besides", "rett syndrome besides mecp2", "syndrome besides mecp2 and", "besides mecp2 and cdkl5", "and cdkl5 dastidar", "cdkl5 dastidar et", "dastidar et al. 2012", "2012 and", "and htt huntingtin", "huntingtin mcfarland", "mcfarland et al. 2013", "al. 2013 . the", "2013 . the subnuclear", ". the subnuclear localization", "the subnuclear localization of", "subnuclear localization of mecp2", "localization of mecp2 may", "of mecp2 may be", "mecp2 may be affected", "may be affected by", "by binding to the", "binding to the lamin", "to the lamin b", "the lamin b receptor", "b receptor lbr", "lbr guarda", "guarda et al. 2009", "transcription of the mecp2 gene", "of the mecp2 gene is", "the mecp2 gene is known", "mecp2 gene is known to", "gene is known to be", "is known to be regulated", "known to be regulated by", "to be regulated by methylation", "be regulated by methylation of", "regulated by methylation of the", "by methylation of the promoter", "methylation of the promoter and", "of the promoter and the", "the promoter and the first", "promoter and the first intron", "the first intron but", "first intron but the", "intron but the responsible", "but the responsible methyltransferases are", "the responsible methyltransferases are not", "responsible methyltransferases are not known", "are not known nagarajan", "not known nagarajan et", "known nagarajan et al.", "et al. 2008 franklin", "al. 2008 franklin et", "2008 franklin et al.", "et al. 2010 liyanage", "al. 2010 liyanage et", "2010 liyanage et al.", "liyanage et al. 2013 .

translation", "et al. 2013 .

translation of", "al. 2013 .

translation of mecp2", "2013 .

translation of mecp2 mrna", ".

translation of mecp2 mrna is", "of mecp2 mrna is negatively", "mecp2 mrna is negatively regulated", "mrna is negatively regulated by", "is negatively regulated by the", "negatively regulated by the microrna", "regulated by the microrna mir", "by the microrna mir 132.", "the microrna mir 132. transcription", "microrna mir 132. transcription of", "mir 132. transcription of mir", "132. transcription of mir 132", "transcription of mir 132 is", "of mir 132 is regulated", "mir 132 is regulated by", "132 is regulated by bdnf", "is regulated by bdnf signaling", "by bdnf signaling through", "bdnf signaling through an", "signaling through an unknown", "an unknown mechanism klein", "unknown mechanism klein et", "mechanism klein et al.", "et al. 2007 su", "al. 2007 su et", "2007 su et al.", "su et al. 2015 .

binding", "et al. 2015 .

binding of", "al. 2015 .

binding of mecp2", "2015 .

binding of mecp2 to", ".

binding of mecp2 to other", "of mecp2 to other proteins", "mecp2 to other proteins and", "to other proteins and to", "other proteins and to dna", "proteins and to dna is", "and to dna is regulated", "to dna is regulated by", "dna is regulated by posttranslational", "is regulated by posttranslational modifications", "by posttranslational modifications of", "posttranslational modifications of which", "modifications of which phosphorylation", "of which phosphorylation has been", "which phosphorylation has been best", "phosphorylation has been best studied.", "has been best studied. calcium", "been best studied. calcium dependent", "best studied. calcium dependent protein", "studied. calcium dependent protein kinases", "dependent protein kinases pka", "protein kinases pka and", "kinases pka and camk", "and camk iv activated", "camk iv activated by", "iv activated by neuronal", "activated by neuronal membrane depolarization", "neuronal membrane depolarization phosphorylate", "membrane depolarization phosphorylate mecp2", "depolarization phosphorylate mecp2 at", "phosphorylate mecp2 at threonine residue", "mecp2 at threonine residue t308", "threonine residue t308 corresponding", "residue t308 corresponding to", "t308 corresponding to t320", "corresponding to t320 in the", "to t320 in the longer", "t320 in the longer mecp2", "in the longer mecp2 splicing", "the longer mecp2 splicing isoform", "mecp2 splicing isoform mecp2_e1", "splicing isoform mecp2_e1 .", "isoform mecp2_e1 . phosphorylation", "mecp2_e1 . phosphorylation at t308", ". phosphorylation at t308 correlates", "phosphorylation at t308 correlates with", "at t308 correlates with neuronal", "t308 correlates with neuronal activity", "correlates with neuronal activity and", "with neuronal activity and inhibits", "neuronal activity and inhibits binding", "activity and inhibits binding of", "and inhibits binding of mecp2", "inhibits binding of mecp2 to", "binding of mecp2 to the", "of mecp2 to the nuclear", "mecp2 to the nuclear receptor", "to the nuclear receptor co", "the nuclear receptor co repressor", "nuclear receptor co repressor complex", "co repressor complex ncor/smrt", "ncor/smrt ebert et", "ebert et al. 2013 .", "et al. 2013 . in", "al. 2013 . in resting", "2013 . in resting neurons", "in resting neurons mecp2", "resting neurons mecp2 is", "neurons mecp2 is phosphorylated", "mecp2 is phosphorylated at serine", "is phosphorylated at serine residue", "phosphorylated at serine residue s80", "serine residue s80 which", "residue s80 which results", "s80 which results in", "which results in a decreased", "results in a decreased association", "in a decreased association of", "a decreased association of mecp2", "decreased association of mecp2 with", "association of mecp2 with chromatin.", "of mecp2 with chromatin. nuclear", "mecp2 with chromatin. nuclear serine/threonine", "with chromatin. nuclear serine/threonine protein", "chromatin. nuclear serine/threonine protein kinase", "nuclear serine/threonine protein kinase hipk2", "serine/threonine protein kinase hipk2 phosphorylates", "protein kinase hipk2 phosphorylates mecp2", "kinase hipk2 phosphorylates mecp2 on", "hipk2 phosphorylates mecp2 on serine", "phosphorylates mecp2 on serine residue", "mecp2 on serine residue s80", "serine residue s80 bracaglia", "residue s80 bracaglia et", "s80 bracaglia et al.", "bracaglia et al. 2009 .", "et al. 2009 . in", "al. 2009 . in activity", "2009 . in activity induced", ". in activity induced neurons", "activity induced neurons upon", "induced neurons upon neuronal", "neurons upon neuronal membrane", "neuronal membrane depolarization mecp2", "membrane depolarization mecp2 s80", "depolarization mecp2 s80 becomes", "s80 becomes dephosphorylated and", "becomes dephosphorylated and mecp2", "dephosphorylated and mecp2 acquires", "and mecp2 acquires phosphorylation on", "mecp2 acquires phosphorylation on serine", "acquires phosphorylation on serine s423", "on serine s423 corresponding", "serine s423 corresponding to", "s423 corresponding to mouse", "corresponding to mouse mecp2 serine", "to mouse mecp2 serine s421", "mouse mecp2 serine s421 .", "mecp2 serine s421 . camk", "serine s421 . camk iv", "s421 . camk iv is", ". camk iv is one", "camk iv is one of", "iv is one of the", "is one of the kinases", "one of the kinases that", "of the kinases that can", "the kinases that can phosphorylate", "kinases that can phosphorylate mecp2", "that can phosphorylate mecp2 on", "can phosphorylate mecp2 on s423.", "phosphorylate mecp2 on s423. phosphorylation", "mecp2 on s423. phosphorylation of", "on s423. phosphorylation of mecp2", "s423. phosphorylation of mecp2 at", "phosphorylation of mecp2 at s423", "of mecp2 at s423 increases", "mecp2 at s423 increases mecp2", "at s423 increases mecp2 binding", "s423 increases mecp2 binding to", "increases mecp2 binding to chromatin", "binding to chromatin zhou", "to chromatin zhou et", "chromatin zhou et al.", "et al. 2006 tao", "al. 2006 tao et", "2006 tao et al.", "et al. 2009 qiu", "al. 2009 qiu et", "2009 qiu et al.", "qiu et al. 2012 .", "et al. 2012 . aurkb", "al. 2012 . aurkb phosphorylates", "2012 . aurkb phosphorylates mecp2", ". aurkb phosphorylates mecp2 at", "aurkb phosphorylates mecp2 at serine", "phosphorylates mecp2 at serine residue", "mecp2 at serine residue s423", "at serine residue s423 in", "serine residue s423 in dividing", "residue s423 in dividing adult", "s423 in dividing adult neuronal", "in dividing adult neuronal progenitor", "dividing adult neuronal progenitor cells", "neuronal progenitor cells li", "progenitor cells li et", "cells li et al.", "li et al. 2014 .

besides", "et al. 2014 .

besides binding", "al. 2014 .

besides binding to", "2014 .

besides binding to the", ".

besides binding to the ncor/smrt", "binding to the ncor/smrt co", "to the ncor/smrt co repressor", "the ncor/smrt co repressor complex", "co repressor complex lyst", "repressor complex lyst et", "complex lyst et al.", "et al. 2013 ebert", "al. 2013 ebert et", "2013 ebert et al.", "al. 2013 mecp2", "2013 mecp2 binds", "mecp2 binds the sin3a co", "binds the sin3a co repressor", "the sin3a co repressor complex.", "sin3a co repressor complex. this", "co repressor complex. this interaction", "repressor complex. this interaction involves", "complex. this interaction involves the", "this interaction involves the transcriptional", "interaction involves the transcriptional repressor", "involves the transcriptional repressor domain", "the transcriptional repressor domain of", "transcriptional repressor domain of mecp2", "repressor domain of mecp2 and", "domain of mecp2 and the", "of mecp2 and the amino", "mecp2 and the amino terminal", "and the amino terminal part", "the amino terminal part of", "amino terminal part of the", "terminal part of the hdac", "part of the hdac interaction", "of the hdac interaction domain", "hdac interaction domain hid", "domain hid of", "hid of sin3a. hdac1", "of sin3a. hdac1 and hdac2", "sin3a. hdac1 and hdac2 are", "hdac1 and hdac2 are part", "and hdac2 are part of", "hdac2 are part of the", "are part of the sin3a", "part of the sin3a co", "of the sin3a co repressor", "the sin3a co repressor complex", "sin3a co repressor complex that", "co repressor complex that co", "repressor complex that co immunoprecipitates", "complex that co immunoprecipitates with", "that co immunoprecipitates with mecp2", "immunoprecipitates with mecp2 nan", "with mecp2 nan et", "mecp2 nan et al.", "nan et al. 1998 .", "et al. 1998 . while", "al. 1998 . while binding", "1998 . while binding of", ". while binding of mecp2", "while binding of mecp2 to", "binding of mecp2 to sin3a", "of mecp2 to sin3a at", "mecp2 to sin3a at target", "to sin3a at target genes", "sin3a at target genes is", "at target genes is associated", "target genes is associated with", "genes is associated with transcriptional", "is associated with transcriptional repression", "with transcriptional repression binding", "transcriptional repression binding to", "repression binding to creb1", "binding to creb1 at target", "to creb1 at target genes", "creb1 at target genes is", "is associated with transcriptional activation", "with transcriptional activation chahrour", "transcriptional activation chahrour et", "activation chahrour et al.", "et al. 2008 chen", "al. 2008 chen et", "2008 chen et al.", "chen et al. 2013 .", "et al. 2013 . function", "al. 2013 . function of", "2013 . function of mecp2", ". function of mecp2 can", "function of mecp2 can be", "of mecp2 can be affected", "mecp2 can be affected by", "can be affected by binding", "be affected by binding to", "affected by binding to foxg1", "binding to foxg1 another", "to foxg1 another gene", "foxg1 another gene mutated", "another gene mutated in rett", "gene mutated in rett syndrome", "mutated in rett syndrome besides", "in rett syndrome besides mecp2", "rett syndrome besides mecp2 and", "syndrome besides mecp2 and cdkl5", "mecp2 and cdkl5 dastidar", "and cdkl5 dastidar et", "cdkl5 dastidar et al.", "al. 2012 and", "2012 and htt", "huntingtin mcfarland et", "mcfarland et al. 2013 .", "et al. 2013 . the", "al. 2013 . the subnuclear", "2013 . the subnuclear localization", ". the subnuclear localization of", "the subnuclear localization of mecp2", "subnuclear localization of mecp2 may", "localization of mecp2 may be", "of mecp2 may be affected", "mecp2 may be affected by", "may be affected by binding", "affected by binding to the", "by binding to the lamin", "binding to the lamin b", "to the lamin b receptor", "lamin b receptor lbr", "lbr guarda et", "guarda et al. 2009 ." ] }, { "record_id": "GLY_000594_1_667", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9022702", "r hsa", "hsa 9022702", "r hsa 9022702" ] }, { "record_id": "GLY_000594_1_667", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mecp2 regulates", "regulates transcription", "transcription of", "of neuronal", "neuronal ligands", "mecp2 regulates transcription", "regulates transcription of", "transcription of neuronal", "of neuronal ligands", "mecp2 regulates transcription of", "regulates transcription of neuronal", "transcription of neuronal ligands", "mecp2 regulates transcription of neuronal", "regulates transcription of neuronal ligands", "ligands regulated", "regulated by", "by mecp2", "mecp2 include", "include bdnf", "reviewed by", "by li", "li and", "and pozzo", "pozzo miller", "miller 2014", "and khorshidahmad", "khorshidahmad et", "et al.", "al. 2016", "mcgill et", "al. 2006", "samaco et", "al. 2012", "chahrour et", "al. 2008", "and dll1", "li et", "al. 2014", "2014 .", "ligands regulated by", "regulated by mecp2", "by mecp2 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nr1h3", "the control", "control of", "of lipogenesis.", "the liver x", "liver x receptor", "x receptor \u03b1", "\u03b1 lxr\u03b1", "lxr\u03b1 or nr1h3", "lxr\u03b2 nr1h2", "nr1h2 are", "are nuclear receptors", "nuclear receptors that", "receptors that are", "that are activated", "are activated by", "activated by endogenous", "by endogenous oxidized", "endogenous oxidized derivatives", "oxidized derivatives of", "derivatives of cholesterol", "of cholesterol known", "cholesterol known as", "known as oxysterols", "oxysterols janowski", "janowski ba et", "ba et al.", "et al. 1999", "1999 jakobsson", "jakobsson t et", "t et al.", "et al. 2012", "al. 2012 .", "2012 . nr1h2", ". nr1h2 and", "nr1h2 and nr1h3", "and nr1h3 act", "nr1h3 act as", "act as whole", "as whole body", "whole body cholesterol", "body cholesterol sensors", "cholesterol sensors and", "sensors and their", "and their activation", "their activation results", "activation results in", "results in a", "in a net", "a net 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in fatty", "in fatty acid", "fatty acid biosynthesis", "biosynthesis schultz", "schultz jr et", "jr et al.", "al. 2000 .", "2000 . nr1h2", ". nr1h2 &", "& nr1h3 may", "nr1h3 may activate", "may activate lipogenic", "activate lipogenic gene", "lipogenic gene transcription", "gene transcription directly", "transcription directly by", "directly by biding", "by biding lxr", "biding lxr responsive", "lxr responsive element", "element lxre", "lxre found", "found in the", "in the promoter", "the promoter regions", "promoter regions of", "regions of several", "of several genes", "genes such", "such as fatty", "as fatty acid", "fatty acid synthase", "synthase fas", "fas or fasn", "fasn and", "and stearoyl coa", "stearoyl coa desaturase", "coa desaturase 1", "1 scd1", "et al. 2000b", "2000b yoshikawa", "yoshikawa t et", "et al. 2001", "2001 joseph", "joseph sb et", "sb et al.", "et al. 2002", "2002 chu", "chu k et", "k et al.", "et al. 2006", "al. 2006 .", "2006 . mice", ". mice carrying", "mice 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administration of", "administration of the", "of the synthetic", "the synthetic nr1h2", "synthetic nr1h2 or", "nr1h2 or nr1h3", "or nr1h3 ligands", "nr1h3 ligands to", "ligands to mice", "to mice triggered", "mice triggered induction", "triggered induction of", "induction of the", "of the lipogenic", "the lipogenic pathway", "lipogenic pathway and", "pathway and raised", "and raised plasma", "raised plasma triglyceride", "plasma triglyceride levels", "levels schultz", "2000 . these", ". these studies", "these studies demonstrate", "studies demonstrate the", "demonstrate the role", "the role of", "role of nr1h3", "lxr\u03b2 in", "in the control", "the control of", "control of lipogenesis.", "the liver x receptor", "liver x receptor \u03b1", "receptor \u03b1 lxr\u03b1", "\u03b1 lxr\u03b1 or", "or nr1h3 and", "nr1h3 and lxr\u03b2", "and lxr\u03b2 nr1h2", "nr1h2 are nuclear", "are nuclear receptors that", "nuclear receptors that are", "receptors that are activated", "that are activated by", "are activated by endogenous", "activated by endogenous oxidized", "by endogenous oxidized derivatives", "endogenous oxidized derivatives of", "oxidized derivatives of cholesterol", "derivatives of cholesterol known", "of cholesterol known as", "cholesterol known as oxysterols", "as oxysterols janowski", "oxysterols janowski ba", "janowski ba et al.", "ba et al. 1999", "al. 1999 jakobsson", "1999 jakobsson t", "jakobsson t et al.", "t et al. 2012", "et al. 2012 .", "al. 2012 . nr1h2", "2012 . nr1h2 and", ". nr1h2 and nr1h3", "nr1h2 and nr1h3 act", "and nr1h3 act as", "nr1h3 act as whole", "act as whole body", "as whole body cholesterol", "whole body cholesterol sensors", "body cholesterol sensors and", "cholesterol sensors and their", "sensors and their activation", "and their activation results", "their activation results in", "activation results in a", "results in a net", "in a net elimination", "a net elimination of", "net elimination of cholesterol", "elimination of cholesterol from", "of cholesterol from the", "cholesterol from the body", "from the body and", "the body and amelioration", "body and amelioration of", "and amelioration of the", "amelioration of the plasma", "of the plasma lipoprotein", "the plasma lipoprotein profile", "plasma lipoprotein profile by", "lipoprotein profile by mobilizing", "profile by mobilizing cholesterol", "by mobilizing cholesterol from", "mobilizing cholesterol from the", "cholesterol from the periphery", "the periphery venkateswaran", "periphery venkateswaran a", "venkateswaran a et al.", "a et al. 2000", "al. 2000 repa", "2000 repa jj", "repa jj et al.", "jj et al. 2000a", "al. 2000a ishibashi", "2000a ishibashi m", "ishibashi m et al.", "m et al. 2013", "et al. 2013 .", "al. 2013 . nr1h3", ". nr1h3 lxr\u03b1", "lxr\u03b1 and nr1h2", "and nr1h2 lxr\u03b2", "lxr\u03b2 also contribute", "also contribute to lowering", "contribute to lowering of", "to lowering of whole", "lowering of whole body", "of whole body cholesterol", "whole body cholesterol levels", "body cholesterol levels by", "cholesterol levels by shifting", "levels by shifting acetyl", "by shifting acetyl coa", "shifting acetyl coa units", "acetyl coa units from", "coa units from cholesterol", "units from cholesterol de", "from cholesterol de novo", "cholesterol de novo biosynthesis", "de novo biosynthesis to", "novo biosynthesis to fatty", "biosynthesis to fatty acid", "to fatty acid synthesis.", "fatty acid synthesis. nr1h2", "acid synthesis. nr1h2 or", "synthesis. nr1h2 or 3", "nr1h2 or 3 induced", "or 3 induced hepatic", "3 induced hepatic lipogenesis", "induced hepatic lipogenesis in", "hepatic lipogenesis in rodents", "lipogenesis in rodents and", "in rodents and humans", "rodents and humans is", "and humans is mediated", "humans is mediated by", "is mediated by direct", "mediated by direct upregulation", "by direct upregulation of", "direct upregulation of sterol", "upregulation of sterol regulatory", "of sterol regulatory element", "sterol regulatory element binding", "regulatory element binding protein", "element binding protein 1", "protein 1 srebf1", "srebf1 the", "the main regulator of", "main regulator of hepatic", "regulator of hepatic lipogenesis", "of hepatic lipogenesis that", "hepatic lipogenesis that controls", "lipogenesis that controls the", "that controls the transcription", "controls the transcription of", "the transcription of genes", "transcription of genes involved", "of genes involved in", "genes involved in fatty", "involved in fatty acid", "in fatty acid biosynthesis", "acid biosynthesis schultz", "biosynthesis schultz jr", "schultz jr et al.", "jr et al. 2000", "et al. 2000 .", "al. 2000 . nr1h2", "2000 . nr1h2 &", ". nr1h2 & nr1h3", "nr1h2 & nr1h3 may", "& nr1h3 may activate", "nr1h3 may activate lipogenic", "may activate lipogenic gene", "activate lipogenic gene transcription", "lipogenic gene transcription directly", "gene transcription directly by", "transcription directly by biding", "directly by biding lxr", "by biding lxr responsive", "biding lxr responsive element", "responsive element lxre", "lxre found in", "found in the promoter", "in the promoter regions", "the promoter regions of", "promoter regions of several", "regions of several genes", "several genes such", "genes such as", "such as fatty acid", "as fatty acid synthase", "acid synthase fas", "synthase fas or", "or fasn and", "fasn and stearoyl", "and stearoyl coa desaturase", "stearoyl coa desaturase 1", "desaturase 1 scd1", "scd1 repa", "jj et al. 2000b", "al. 2000b yoshikawa", "2000b yoshikawa t", "yoshikawa t et al.", "t et al. 2001", "al. 2001 joseph", "2001 joseph sb", "joseph sb et al.", "sb et al. 2002", "al. 2002 chu", "2002 chu k", "chu k et al.", "k et al. 2006", "et al. 2006 .", "al. 2006 . mice", "2006 . mice carrying", ". mice carrying a", "mice carrying a targeted", "carrying a targeted disruption", "a targeted disruption in", "targeted disruption in the", "disruption in the nr1h3", "the nr1h3 lxr\u03b1", "lxr\u03b1 gene were", "gene were deficient in", "were deficient in expression", "deficient in expression of", "in expression of fas", "of fas scd1", "acc and srebf1", "and srebf1 peet", "srebf1 peet dj", "peet dj et al.", "dj et al. 1998", "et al. 1998 .", "al. 1998 . mice", "1998 . mice ablated", ". mice ablated of", "mice ablated of both", "ablated of both nr1h3", "of both nr1h3 and", "both nr1h3 and nr1h2", "nr1h3 and nr1h2 showed", "and nr1h2 showed defective", "nr1h2 showed defective hepatic", "showed defective hepatic lipid", "defective hepatic lipid metabolism", "hepatic lipid metabolism decreasing", "lipid metabolism decreasing lipogenesis", "metabolism decreasing lipogenesis by", "decreasing lipogenesis by 80%", "lipogenesis by 80% and", "by 80% and were", "80% and were resistant", "and were resistant to", "were resistant to obesity", "to obesity repa", "obesity repa jj", "jj et al. 2000", "al. 2000 kalaany", "2000 kalaany ny", "kalaany ny et al.", "ny et al. 2005", "al. 2005 beaven", "2005 beaven sw", "beaven sw et al.", "sw et al. 2013", "al. 2013 . further", ". further the", "further the administration", "the administration of the", "administration of the synthetic", "of the synthetic nr1h2", "the synthetic nr1h2 or", "synthetic nr1h2 or nr1h3", "nr1h2 or nr1h3 ligands", "or nr1h3 ligands to", "nr1h3 ligands to mice", "ligands to mice triggered", "to mice triggered induction", "mice triggered induction of", "triggered induction of the", "induction of the lipogenic", "of the lipogenic pathway", "the lipogenic pathway and", "lipogenic pathway and raised", "pathway and raised plasma", "and raised plasma triglyceride", "raised plasma triglyceride levels", "triglyceride levels schultz", "levels schultz jr", "al. 2000 . these", "2000 . these studies", ". these studies demonstrate", "these studies demonstrate the", "studies demonstrate the role", "demonstrate the role of", "the role of nr1h3", "of nr1h3 lxr\u03b1", "lxr\u03b2 in the", "in the control of", "the control of lipogenesis.", "the liver x receptor \u03b1", "x receptor \u03b1 lxr\u03b1", "receptor \u03b1 lxr\u03b1 or", "\u03b1 lxr\u03b1 or nr1h3", "lxr\u03b1 or nr1h3 and", "or nr1h3 and lxr\u03b2", "lxr\u03b2 nr1h2 are", "nr1h2 are nuclear receptors", "are nuclear receptors that are", "nuclear receptors that are activated", "receptors that are activated by", "that are activated by endogenous", "are activated by endogenous oxidized", "activated by endogenous oxidized derivatives", "by endogenous oxidized derivatives of", "endogenous oxidized derivatives of cholesterol", "oxidized derivatives of cholesterol known", "derivatives of cholesterol known as", "of cholesterol known as oxysterols", "known as oxysterols janowski", "as oxysterols janowski ba", "oxysterols janowski ba et", "janowski ba et al. 1999", "et al. 1999 jakobsson", "al. 1999 jakobsson t", "1999 jakobsson t et", "jakobsson t et al. 2012", "t et al. 2012 .", "et al. 2012 . nr1h2", "al. 2012 . nr1h2 and", "2012 . nr1h2 and nr1h3", ". nr1h2 and nr1h3 act", "nr1h2 and nr1h3 act as", "and nr1h3 act as whole", "nr1h3 act as whole body", "act as whole body cholesterol", "as whole body cholesterol sensors", "whole body cholesterol sensors and", "body cholesterol sensors and their", "cholesterol sensors and their activation", "sensors and their activation results", "and their activation results in", "their activation results in a", "activation results in a net", "results in a net elimination", "in a net elimination of", "a net elimination of cholesterol", "net elimination of cholesterol from", "elimination of cholesterol from the", "of cholesterol from the body", "cholesterol from the body and", "from the body and amelioration", "the body and amelioration of", "body and amelioration of the", "and amelioration of the plasma", "amelioration of the plasma lipoprotein", "of the plasma lipoprotein profile", "the plasma lipoprotein profile by", "plasma lipoprotein profile by mobilizing", "lipoprotein profile by mobilizing cholesterol", "profile by mobilizing cholesterol from", "by mobilizing cholesterol from the", "mobilizing cholesterol from the periphery", "from the periphery venkateswaran", "the periphery venkateswaran a", "periphery venkateswaran a et", "venkateswaran a et al. 2000", "et al. 2000 repa", "al. 2000 repa jj", "2000 repa jj et", "repa jj et al. 2000a", "et al. 2000a ishibashi", "al. 2000a ishibashi m", "2000a ishibashi m et", "ishibashi m et al. 2013", "m et al. 2013 .", "et al. 2013 . nr1h3", "2013 . nr1h3 lxr\u03b1", "nr1h3 lxr\u03b1 and", "nr1h2 lxr\u03b2 also", "lxr\u03b2 also contribute to", "also contribute to lowering of", "contribute to lowering of whole", "to lowering of whole body", "lowering of whole body cholesterol", "of whole body cholesterol levels", "whole body cholesterol levels by", "body cholesterol levels by shifting", "cholesterol levels by shifting acetyl", "levels by shifting acetyl coa", "by shifting acetyl coa units", "shifting acetyl coa units from", "acetyl coa units from cholesterol", "coa units from cholesterol de", "units from cholesterol de novo", "from cholesterol de novo biosynthesis", "cholesterol de novo biosynthesis to", "de novo biosynthesis to fatty", "novo biosynthesis to fatty acid", "biosynthesis to fatty acid synthesis.", "to fatty acid synthesis. nr1h2", "fatty acid synthesis. nr1h2 or", "acid synthesis. nr1h2 or 3", "synthesis. nr1h2 or 3 induced", "nr1h2 or 3 induced hepatic", "or 3 induced hepatic lipogenesis", "3 induced hepatic lipogenesis in", "induced hepatic lipogenesis in rodents", "hepatic lipogenesis in rodents and", "lipogenesis in rodents and humans", "in rodents and humans is", "rodents and humans is mediated", "and humans is mediated by", "humans is mediated by direct", "is mediated by direct upregulation", "mediated by direct upregulation of", "by direct upregulation of sterol", "direct upregulation of sterol regulatory", "upregulation of sterol regulatory element", "of sterol regulatory element binding", "sterol regulatory element binding protein", "regulatory element binding protein 1", "binding protein 1 srebf1", "srebf1 the main", "the main regulator of hepatic", "main regulator of hepatic lipogenesis", "regulator of hepatic lipogenesis that", "of hepatic lipogenesis that controls", "hepatic lipogenesis that controls the", "lipogenesis that controls the transcription", "that controls the transcription of", "controls the transcription of genes", "the transcription of genes involved", "transcription of genes involved in", "of genes involved in fatty", "genes involved in fatty acid", "involved in fatty acid biosynthesis", "fatty acid biosynthesis schultz", "acid biosynthesis schultz jr", "biosynthesis schultz jr et", "schultz jr et al. 2000", "jr et al. 2000 .", "et al. 2000 . nr1h2", "al. 2000 . nr1h2 &", "2000 . nr1h2 & nr1h3", ". nr1h2 & nr1h3 may", "nr1h2 & nr1h3 may activate", "& nr1h3 may activate lipogenic", "nr1h3 may activate lipogenic gene", "may activate lipogenic gene transcription", "activate lipogenic gene transcription directly", "lipogenic gene transcription directly by", "gene transcription directly by biding", "transcription directly by biding lxr", "directly by biding lxr responsive", "by biding lxr responsive element", "lxr responsive element lxre", "element lxre found", "lxre found in the", "found in the promoter regions", "in the promoter regions of", "the promoter regions of several", "promoter regions of several genes", "of several genes such", "several genes such as", "genes such as fatty", "such as fatty acid synthase", "fatty acid synthase fas", "acid synthase fas or", "synthase fas or fasn", "fas or fasn and", "or fasn and stearoyl", "fasn and stearoyl coa", "and stearoyl coa desaturase 1", "coa desaturase 1 scd1", "scd1 repa jj", "repa jj et al. 2000b", "et al. 2000b yoshikawa", "al. 2000b yoshikawa t", "2000b yoshikawa t et", "yoshikawa t et al. 2001", "et al. 2001 joseph", "al. 2001 joseph sb", "2001 joseph sb et", "joseph sb et al. 2002", "et al. 2002 chu", "al. 2002 chu k", "2002 chu k et", "chu k et al. 2006", "k et al. 2006 .", "et al. 2006 . mice", "al. 2006 . mice carrying", "2006 . mice carrying a", ". mice carrying a targeted", "mice carrying a targeted disruption", "carrying a targeted disruption in", "a targeted disruption in the", "targeted disruption in the nr1h3", "in the nr1h3 lxr\u03b1", "nr1h3 lxr\u03b1 gene", "lxr\u03b1 gene were deficient", "gene were deficient in expression", "were deficient in expression of", "deficient in expression of fas", "expression of fas scd1", "fas scd1 acc", "scd1 acc and", "and srebf1 peet dj", "srebf1 peet dj et", "peet dj et al. 1998", "dj et al. 1998 .", "et al. 1998 . mice", "al. 1998 . mice ablated", "1998 . mice ablated of", ". mice ablated of both", "mice ablated of both nr1h3", "ablated of both nr1h3 and", "of both nr1h3 and nr1h2", "both nr1h3 and nr1h2 showed", "nr1h3 and nr1h2 showed defective", "and nr1h2 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nr1h2 or nr1h3", "synthetic nr1h2 or nr1h3 ligands", "nr1h2 or nr1h3 ligands to", "or nr1h3 ligands to mice", "nr1h3 ligands to mice triggered", "ligands to mice triggered induction", "to mice triggered induction of", "mice triggered induction of the", "triggered induction of the lipogenic", "induction of the lipogenic pathway", "of the lipogenic pathway and", "the lipogenic pathway and raised", "lipogenic pathway and raised plasma", "pathway and raised plasma triglyceride", "and raised plasma triglyceride levels", "plasma triglyceride levels schultz", "triglyceride levels schultz jr", "levels schultz jr et", "et al. 2000 . these", "al. 2000 . these studies", "2000 . these studies demonstrate", ". these studies demonstrate the", "these studies demonstrate the role", "studies demonstrate the role of", "demonstrate the role of nr1h3", "role of nr1h3 lxr\u03b1", "nr1h2 lxr\u03b2 in", "lxr\u03b2 in the control", "in the control of lipogenesis." ] }, { "record_id": "GLY_000594_1_670", 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"dahlman\u2011wright k 2010", "2010 ma", "ma z et", "z et al.", "et al. 2017", "al. 2017 .", "2017 . in", ". in peripheral", "in peripheral cells", "peripheral cells such", "cells such as", "such as macrophages", "macrophages nr1h2", "nr1h2 and nr1h3", "and nr1h3 increase", "nr1h3 increase cholesterol", "increase cholesterol efflux", "cholesterol efflux by", "efflux by inducing", "by inducing expression", "inducing expression of", "expression of atp", "of atp binding", "atp binding cassette", "binding cassette subfamily", "cassette subfamily a", "subfamily a type", "a type 1", "1 abca1", "abcg1 and", "and apolipoprotein apoe", "apoe jakobsson", "jakobsson t et", "t et al.", "et al. 2009", "2009 laffitte", "laffitte ba et", "et al. 2001", "2001 mak", "mak pa et", "pa et al.", "et al. 2002", "al. 2002 .", "2002 . in", ". in the", "in the intestine", "intestine lxr", "lxr agonists decrease", "agonists decrease cholesterol", "decrease cholesterol absorption", "cholesterol absorption through", "absorption through induction", "through induction of", "induction of abca1", "abca1 abcg5", "abcg5 and", "abcg8 repa", "repa jj et", "jj et al.", "et al. 2000", "2000 back", "back ss et", "ss et al.", "et al. 2013", "al. 2013 .", "2013 . cholesterol", ". cholesterol removal", "cholesterol removal from", "removal from non", "from non hepatic", "non hepatic peripheral", "hepatic peripheral cells", "such as lipid", "as lipid laden", "lipid laden macrophages", "macrophages and", "and its delivery", "its delivery back", "delivery back to", "back to the", "to the liver", "the liver for", "liver for catabolism", "for catabolism and", "catabolism and excretion", "and excretion are", "excretion are processes", "are processes collectively", "processes collectively known", "collectively known as", "known as reverse", "as reverse cholesterol", "reverse cholesterol transport", "transport rct", "francis ga 2010", "2010 rosenson", "rosenson rs et", "rs et al.", "et al. 2012", "al. 2012 .", "2012 . this", ". this reactome", "this reactome module", "reactome module describes", "module describes the", "describes the activation", "the activation of", "activation of several", "of several direct", "several direct nr1h2", "direct nr1h2 3", "nr1h2 3 target", "3 target genes", "target genes that", "genes that are", "that are closely", "are closely associated", "closely associated with", "associated with the", "with the rct", "the rct pathway", "pathway including", "including genes encoding", "genes encoding membrane", "encoding membrane lipid", "membrane lipid transporters", "transporters such", "abca1 abcg1", "abcg1 abcg5", "abcg5 abcg8", "abcg8 and a", "and a cluster", "a cluster of", "cluster of apolipoprotein", "of apolipoprotein genes", "apolipoprotein genes apoe", "apoe apoc1", "apoc1 apoc2", "apoc2 and apoc4", "apoc4 jakobsson", "2009 back", "2013 mak", "the liver x receptors", "x receptors lxrs", "lxrs lxr\u03b1", "nr1h3 and lxr\u03b2", "and lxr\u03b2 nr1h2", "nr1h2 are", "are nuclear receptors that", "nuclear receptors that are", "receptors that are activated", "that are activated by", "are activated by endogenous", "activated by endogenous oxysterols", "endogenous oxysterols oxidized", "oxysterols oxidized derivatives", "oxidized derivatives of cholesterol", "of cholesterol janowski", "cholesterol janowski ba", "janowski ba et al.", "ba et al. 1996", "et al. 1996 .", "al. 1996 . when", "1996 . when cellular", ". when cellular oxysterols", "when cellular oxysterols accumulate", "cellular oxysterols accumulate as", "oxysterols accumulate as a", "accumulate as a result", "as a result of", "a result of increasing", "result of increasing concentrations", "of increasing concentrations of", "increasing concentrations of cholesterol", "of cholesterol nr1h2", "cholesterol nr1h2 3", "nr1h2 3 induce the", "3 induce the transcription", "induce the transcription of", "the transcription of genes", "transcription of genes that", "of genes that protect", "genes that protect cells", "that protect cells from", "protect cells from cholesterol", "cells from cholesterol overload", "cholesterol overload zhao", "overload zhao c", "zhao c & dahlman\u2011wright", "c & dahlman\u2011wright k", "& dahlman\u2011wright k 2010", "k 2010 ma", "2010 ma z", "ma z et al.", "z et al. 2017", "et al. 2017 .", "al. 2017 . in", "2017 . in peripheral", ". in peripheral cells", "in peripheral cells such", "peripheral cells such as", "cells such as macrophages", "as macrophages nr1h2", "macrophages nr1h2 and", "nr1h2 and nr1h3 increase", "and nr1h3 increase cholesterol", "nr1h3 increase cholesterol efflux", "increase cholesterol efflux by", "cholesterol efflux by inducing", "efflux by inducing expression", "by inducing expression of", "inducing expression of atp", "expression of atp binding", "of atp binding cassette", "atp binding cassette subfamily", "binding cassette subfamily a", "cassette subfamily a type", "subfamily a type 1", "type 1 abca1", "abcg1 and apolipoprotein", "apolipoprotein apoe jakobsson", "apoe jakobsson t", "jakobsson t et al.", "t et al. 2009", "al. 2009 laffitte", "2009 laffitte ba", "laffitte ba et al.", "ba et al. 2001", "al. 2001 mak", "2001 mak pa", "mak pa et al.", "pa et al. 2002", "et al. 2002 .", "al. 2002 . in", "2002 . in the", ". in the intestine", "the intestine lxr", "intestine lxr agonists", "lxr agonists decrease cholesterol", "agonists decrease cholesterol absorption", "decrease cholesterol absorption through", "cholesterol absorption through induction", "absorption through induction of", "through induction of abca1", "of abca1 abcg5", "abcg5 and abcg8", "and abcg8 repa", "abcg8 repa jj", "repa jj et al.", "jj et al. 2000", "al. 2000 back", "2000 back ss", "back ss et al.", "ss et al. 2013", "et al. 2013 .", "al. 2013 . cholesterol", "2013 . cholesterol removal", ". cholesterol removal from", "cholesterol removal from non", "removal from non hepatic", "from non hepatic peripheral", "non hepatic peripheral cells", "such as lipid laden", "as lipid laden macrophages", "laden macrophages and", "macrophages and its", "and its delivery back", "its delivery back to", "delivery back to the", "back to the liver", "to the liver for", "the liver for catabolism", "liver for catabolism and", "for catabolism and excretion", "catabolism and excretion are", "and excretion are processes", "excretion are processes collectively", "are processes collectively known", "processes collectively known as", "collectively known as reverse", "known as reverse cholesterol", "as reverse cholesterol transport", "cholesterol transport rct", "rct francis", "ga 2010 rosenson", "2010 rosenson rs", "rosenson rs et al.", "rs et al. 2012", "et al. 2012 .", "al. 2012 . this", "2012 . this reactome", ". this reactome module", "this reactome module describes", "reactome module describes the", "module describes the activation", "describes the activation of", "the activation of several", "activation of several direct", "of several direct nr1h2", "several direct nr1h2 3", "direct nr1h2 3 target", "nr1h2 3 target genes", "3 target genes that", "target genes that are", "genes that are closely", "that are closely associated", "are closely associated with", "closely associated with the", "associated with the rct", "with the rct pathway", "rct pathway including", "pathway including genes", "including genes encoding membrane", "genes encoding membrane lipid", "encoding membrane lipid transporters", "lipid transporters such", "transporters such abca1", "such abca1 abcg1", "abcg5 abcg8 and", "abcg8 and a cluster", "and a cluster of", "a cluster of apolipoprotein", "cluster of apolipoprotein genes", "of apolipoprotein genes apoe", "genes apoe apoc1", "apoc1 apoc2 and", "and apoc4 jakobsson", "apoc4 jakobsson t", "al. 2009 back", "2009 back ss", "al. 2013 mak", "2013 mak pa", "liver x receptors lxrs", "lxr\u03b1 nr1h3 and", "nr1h2 are nuclear", "are nuclear receptors that are", "nuclear receptors that are activated", "receptors that are activated by", "that are activated by endogenous", "are activated by endogenous oxysterols", "by endogenous oxysterols oxidized", "endogenous oxysterols oxidized derivatives", "oxysterols oxidized derivatives of", "derivatives of cholesterol janowski", "of cholesterol janowski ba", "cholesterol janowski ba et", "janowski ba et al. 1996", "ba et al. 1996 .", "et al. 1996 . when", "al. 1996 . when cellular", "1996 . when cellular oxysterols", ". when cellular oxysterols accumulate", "when cellular oxysterols accumulate as", "cellular oxysterols accumulate as a", "oxysterols accumulate as a result", "accumulate as a result of", "as a result of increasing", "a result of increasing concentrations", "result of increasing concentrations of", "of increasing concentrations of cholesterol", "concentrations of cholesterol nr1h2", "of cholesterol nr1h2 3", "cholesterol nr1h2 3 induce", "nr1h2 3 induce the transcription", "3 induce the transcription of", "induce the transcription of genes", "the transcription of genes that", "transcription of genes that protect", "of genes that protect cells", "genes that protect cells from", "that protect cells from cholesterol", "protect cells from cholesterol overload", "from cholesterol overload zhao", "cholesterol overload zhao c", "overload zhao c &", "zhao c & dahlman\u2011wright k", "c & dahlman\u2011wright k 2010", "dahlman\u2011wright k 2010 ma", "k 2010 ma z", "2010 ma z et", "ma z et al. 2017", "z et al. 2017 .", "et al. 2017 . in", "al. 2017 . in peripheral", "2017 . in peripheral cells", ". in peripheral cells such", "in peripheral cells such as", "peripheral cells such as macrophages", "such as macrophages nr1h2", "as macrophages nr1h2 and", "macrophages nr1h2 and nr1h3", "nr1h2 and nr1h3 increase cholesterol", "and nr1h3 increase cholesterol efflux", "nr1h3 increase cholesterol efflux by", "increase cholesterol efflux by inducing", "cholesterol efflux by inducing expression", "efflux by inducing expression of", "by inducing expression of atp", "inducing expression of atp binding", "expression of atp binding cassette", "of atp binding cassette subfamily", "atp binding cassette subfamily a", "binding cassette subfamily a type", "cassette subfamily a type 1", "a type 1 abca1", "abcg1 and apolipoprotein apoe", "and apolipoprotein apoe jakobsson", "apolipoprotein apoe jakobsson t", "apoe jakobsson t et", "jakobsson t et al. 2009", "et al. 2009 laffitte", "al. 2009 laffitte ba", "2009 laffitte ba et", "laffitte ba et al. 2001", "et al. 2001 mak", "al. 2001 mak pa", "2001 mak pa et", "mak pa et al. 2002", "pa et al. 2002 .", "et al. 2002 . in", "al. 2002 . in the", "2002 . in the intestine", "in the intestine lxr", "the intestine lxr agonists", "intestine lxr agonists decrease", "lxr agonists decrease cholesterol absorption", "agonists decrease cholesterol absorption through", "decrease cholesterol absorption through induction", "cholesterol absorption through induction of", "absorption through induction of abca1", "induction of abca1 abcg5", "abca1 abcg5 and", "and abcg8 repa jj", "abcg8 repa jj et", "repa jj et al. 2000", "et al. 2000 back", "al. 2000 back ss", "2000 back ss et", "back ss et al. 2013", "ss et al. 2013 .", "et al. 2013 . cholesterol", "al. 2013 . cholesterol removal", "2013 . cholesterol removal from", ". cholesterol removal from non", "cholesterol removal from non hepatic", "removal from non hepatic peripheral", "from non hepatic peripheral cells", "hepatic peripheral cells such", "cells such as lipid", "such as lipid laden macrophages", "lipid laden macrophages and", "laden macrophages and its", "macrophages and its delivery", "and its delivery back to", "its delivery back to the", "delivery back to the liver", "back to the liver for", "to the liver for catabolism", "the liver for catabolism and", "liver for catabolism and excretion", "for catabolism and excretion are", "catabolism and excretion are processes", "and excretion are processes collectively", "excretion are processes collectively known", "are processes collectively known as", "processes collectively known as reverse", "collectively known as reverse cholesterol", "known as reverse cholesterol transport", "reverse cholesterol transport rct", "rct francis ga", "francis ga 2010 rosenson", "ga 2010 rosenson rs", "2010 rosenson rs et", "rosenson rs et al. 2012", "rs et al. 2012 .", "et al. 2012 . this", "al. 2012 . this reactome", "2012 . this reactome module", ". this reactome module describes", "this reactome module describes the", "reactome module describes the activation", "module describes the activation of", "describes the activation of several", "the activation of several direct", "activation of several direct nr1h2", "of several direct nr1h2 3", "several direct nr1h2 3 target", "direct nr1h2 3 target genes", "nr1h2 3 target genes that", "3 target genes that are", "target genes that are closely", "genes that are closely associated", "that are closely associated with", "are closely associated with the", "closely associated with the rct", "associated with the rct pathway", "the rct pathway including", "rct pathway including genes", "pathway including genes encoding", "including genes encoding membrane lipid", "genes encoding membrane lipid transporters", "membrane lipid transporters such", "lipid transporters such abca1", "abca1 abcg1 abcg5", "abcg1 abcg5 abcg8", "abcg5 abcg8 and a", "abcg8 and a cluster of", "and a cluster of apolipoprotein", "a cluster of apolipoprotein genes", "cluster of apolipoprotein genes apoe", "apolipoprotein genes apoe apoc1", "apoe apoc1 apoc2", "apoc1 apoc2 and apoc4", "apoc2 and apoc4 jakobsson", "and apoc4 jakobsson t", "apoc4 jakobsson t et", "et al. 2009 back", "al. 2009 back ss", "2009 back ss et", "et al. 2013 mak", "al. 2013 mak pa", "2013 mak pa et" ] }, { "record_id": "GLY_000594_1_671", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9033241", "r hsa", "hsa 9033241", "r hsa 9033241" ] }, { "record_id": "GLY_000594_1_671", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "peroxisomal protein", "protein import", "peroxisomal protein import", "peroxisomes are", "are small", "small cellular", "cellular organelles", "organelles that", "that are", "are bounded", "bounded by", "by a", "a single", "single membrane", "membrane and", "and contain", "contain variable", "variable compositions", "compositions of", "of proteins", "proteins depending", "depending on", "on cell", "cell type.", "type. peroxisomes", "peroxisomes function", "function in", "in oxidation", "oxidation of", "of fatty", "fatty acids", "detoxification of", "of glyoxylate", "and synthesis", "synthesis of", "of plasmalogens", "glycerophospholipids containing", "containing an", "an alcohol", "alcohol with", "with a", "a vinyl", "vinyl ether", "ether bond", "reviewed in", "in lohdi", "lohdi and", "and semenkovich", "semenkovich 2014", "2014 .", ". all", "all of", "of the", "the approximately", "approximately 46", "46 proteins", "proteins contained", "contained in", "in peroxisomal", "peroxisomal matrix", "matrix are", "are imported", "imported from", "from the", "the cytosol", "cytosol by", "a unique", "unique mechanism", "mechanism that", "that does", "does not", "not require", "require the", "the imported", "imported proteins", "proteins to", "to be", "be unfolded", "unfolded as", "as they", "they cross", "cross the", "the membrane", "walton et", "et al.", "al. 1995", "in ma", "ma et", "al. 2011", "fujiki et", "al. 2014", "baker et", "al. 2016", "dias et", "et al", "al 2016", "emmanoulidis et", "erdmann 2016", "francisco et", "al. 2017", "2017 .", ". the", "the incompletely", "incompletely characterized", "characterized process", "process appears", "appears to", "to involve", "involve the", "the transport", "transport of", "the proteins", "proteins through", "through a", "a variably", "variably sized", "sized pore", "pore in", "in the", "membrane comprising", "comprising at", "at least", "least pex5", "pex5 and", "and pex14", "inferred from", "the yeast", "yeast homologs", "homologs in", "in meinecke", "meinecke et", "al. 2010", "yeast pore", "pore is", "is reviewed", "2016 .", ". oligomeric", "oligomeric proteins", "proteins are", "are also", "also observed", "observed to", "to cross", "the peroxisomal", "peroxisomal membrane", "otera and", "and fujiki", "fujiki 2012", "but their", "their transport", "transport appears", "be less", "less efficient", "efficient than", "than monomeric", "monomeric proteins", "freitas et", "from mouse", "mouse homologs", "in freitas", "al. 2015", "in dias", "2016 .
in", ".
in the", "receptor proteins", "and pex7", "bind to", "to specific", "specific sequence", "sequence motifs", "motifs in", "in cargo", "cargo proteins", "dodt et", "wiemer et", "braverman et", "al. 1997", "1997 .", "the long", "long and", "and short", "short isoforms", "isoforms of", "of pex5", "pex5l and", "and pex5s", "bind peroxisome", "peroxisome targeting", "targeting sequence", "sequence 1", "originally identified", "identified in", "in firefly", "firefly luciferase", "luciferase by", "by gould", "gould et", "al. 1989", "found on", "on most", "most peroxisomal", "matrix proteins", "pex7 binds", "binds pts2", "in rat", "rat 3", "3 ketoacyl", "ketoacyl coa", "coa thiolase", "thiolase by", "by swinkels", "swinkels et", "al. 1991", "on 3", "3 imported", "proteins thus", "thus far", "far in", "in humans.", "humans. the", "long isoform", "isoform of", "then binds", "binds the", "the pex7:cargo", "pex7:cargo protein", "protein complex", "al. 1998", "otera et", "al. 2000", "2000 .", ". pex5s", "pex5s l", "l bound", "bound to", "to a", "a cargo", "cargo protein", "protein or", "or pex5l", "pex5l bound", "to pex7:cargo", "protein then", "then interacts", "interacts with", "a complex", "complex comprising", "comprising pex13", "and pex12", "pex12 at", "at the", "al. 1996", "fransen et", "from rat", "rat homologs", "in reguenga", "reguenga et", "al. 2001", "2001 .
the", ".
the ensuing", "ensuing step", "step in", "in which", "which the", "the cargo", "protein is", "is translocated", "translocated across", "across the", "membrane is", "is not", "not completely", "completely understood.", "understood. during", "during translocation", "pex7 become", "become inserted", "inserted into", "into the", "oliveira et", "al. 2003", "and expose", "expose a", "a portion", "portion of", "of their", "their polypeptide", "polypeptide chains", "chains to", "to the", "the organellar", "organellar matrix", "rodrigues et", "2015 .", ". one", "one current", "current model", "model envisages", "envisages pex5", "pex5 as", "as a", "a plunger", "plunger that", "that inserts", "inserts into", "into a", "a transmembrane", "transmembrane barrel", "barrel formed", "formed by", "by pex14", "the docking", "docking translocation", "translocation module", "2017 .
after", ".
after delivering", "delivering cargo", "cargo to", "the matrix", "pex7 are", "are recycled", "recycled back", "back to", "a process", "process requiring", "requiring mono", "mono ubiquitination", "ubiquitination of", "and atp", "atp hydrolysis", "imanaka et", "al. 1987", "thoms and", "and erdmann", "erdmann 2006", "carvalho et", "al. 2007", "2007 .", ". pex7", "pex7 is", "not ubiquitinated", "ubiquitinated but", "but its", "its recycling", "recycling requires", "requires pex5", "pex5 mono", "mono ubiquitination.", "ubiquitination. a", "a subcomplex", "subcomplex of", "module comprising", "comprising the", "the ring", "ring finger", "finger proteins", "proteins pex2", "pex12 conjugates", "conjugates a", "single ubiquitin", "ubiquitin to", "a cysteine", "cysteine residue", "residue of", "in platta", "platta et", "the mono", "mono ubiquitinated", "ubiquitinated pex5", "and associated", "associated pex7", "are then", "then extracted", "extracted by", "by the", "the exportomer", "exportomer complex", "complex consisting", "consisting of", "of pex1", "and zfand6", "in miyata", "miyata et", "al. 2012", "2012 .", ". pex1", "pex1 and", "and pex6", "pex6 are", "are members", "members of", "the atpases", "atpases associated", "associated with", "with diverse", "diverse cellular", "cellular activities", "a group", "group of", "proteins that", "that use", "use the", "the energy", "energy of", "of atp", "hydrolysis to", "to remodel", "remodel molecular", "molecular complexes.", "complexes. pex1", "pex6 form", "form a", "a hetero", "hetero hexameric", "hexameric ring", "best described", "described as", "a trimer", "trimer of", "of pex1/pex6", "pex1/pex6 dimers", "from yeast", "yeast in", "al. 2005", "homologs reviewed", "in schwerter", "schwerter et", ". data", "data on", "on the", "yeast pex1:pex6", "pex1:pex6 complex", "complex suggest", "suggest that", "that these", "these atpases", "atpases use", "use a", "a substrate", "substrate threading", "threading mechanism", "mechanism to", "to disrupt", "disrupt protein", "protein protein", "protein interactions", "gardner et", "al. 2018", "2018 .", "is also", "also then", "then returned", "returned to", ". once", "once in", "pex5 is", "is enzymatically", "enzymatically deubiquitinated", "deubiquitinated by", "by usp9x", "usp9x and", "and may", "may also", "also be", "be non", "non enzymatically", "by nucleophilic", "nucleophilic attack", "attack of", "the thioester", "thioester bond", "bond between", "between ubiquitin", "ubiquitin and", "and the", "the cysteine", "pex5 by", "by small", "small metabolites", "metabolites such", "such as", "as glutathione", "grou et", "2012 .
defects", ".
defects in", "peroxisomal import", "import cause", "cause human", "human diseases:", "diseases: zellweger", "zellweger syndrome", "neonatal adrenoleukodystrophy", "infantile refsum", "refsum disease", "disease and", "and rhizomelic", "rhizomelic chondrodysplasia", "chondrodysplasia punctata", "punctata types", "types 1", "1 and", "and 5", "bar\u00f8y et", "in nagotu", "nagotu et", "al. 2013", "wanders 2014", "fujiki 2016", "waterham et", "peroxisomes are small", "are small cellular", "small cellular organelles", "cellular organelles that", "organelles that are", "that are bounded", "are bounded by", "bounded by a", "by a single", "a single membrane", "single membrane and", "membrane and contain", "and contain variable", "contain variable compositions", "variable compositions of", "compositions of proteins", "of proteins depending", "proteins depending on", "depending on cell", "on cell type.", "cell type. peroxisomes", "type. peroxisomes function", "peroxisomes function in", "function in oxidation", "in oxidation of", "oxidation of fatty", "of fatty acids", "acids detoxification", "detoxification of glyoxylate", "glyoxylate and", "and synthesis of", "synthesis of plasmalogens", "plasmalogens glycerophospholipids", "glycerophospholipids containing an", "containing an alcohol", "an alcohol with", "alcohol with a", "with a vinyl", "a vinyl ether", "vinyl ether bond", "bond reviewed", "reviewed in lohdi", "in lohdi and", "lohdi and semenkovich", "and semenkovich 2014", "semenkovich 2014 .", "2014 . all", ". all of", "all of the", "of the approximately", "the approximately 46", "approximately 46 proteins", "46 proteins contained", "proteins contained in", "contained in peroxisomal", "in peroxisomal matrix", "peroxisomal matrix are", "matrix are imported", "are imported from", "imported from the", "from the cytosol", "the cytosol by", "cytosol by a", "by a unique", "a unique mechanism", "unique mechanism that", "mechanism that does", "that does not", "does not require", "not require the", "require the imported", "the imported proteins", "imported proteins to", "proteins to be", "to be unfolded", "be unfolded as", "unfolded as they", "as they cross", "they cross the", "cross the membrane", "membrane walton", "walton et al.", "et al. 1995", "1995 reviewed", "reviewed in ma", "in ma et", "ma et al.", "et al. 2011", "2011 fujiki", "fujiki et al.", "et al. 2014", "2014 baker", "baker et al.", "et al. 2016", "2016 dias", "dias et al", "et al 2016", "2016 emmanoulidis", "emmanoulidis et al.", "2016 erdmann", "2016 francisco", "francisco et al.", "et al. 2017", "al. 2017 .", "2017 . the", ". the incompletely", "the incompletely characterized", "incompletely characterized process", "characterized process appears", "process appears to", "appears to involve", "to involve the", "involve the transport", "the transport of", "transport of the", "of the proteins", "the proteins through", "proteins through a", "through a variably", "a variably sized", "variably sized pore", "sized pore in", "pore in the", "in the membrane", "the membrane comprising", "membrane comprising at", "comprising at least", "at least pex5", "least pex5 and", "pex5 and pex14", "pex14 inferred", "inferred from the", "from the yeast", "the yeast homologs", "yeast homologs in", "homologs in meinecke", "in meinecke et", "meinecke et al.", "et al. 2010", "2010 the", "the yeast pore", "yeast pore is", "pore is reviewed", "is reviewed in", "reviewed in meinecke", "al. 2016 .", "2016 . oligomeric", ". oligomeric proteins", "oligomeric proteins are", "proteins are also", "are also observed", "also observed to", "observed to cross", "to cross the", "cross the peroxisomal", "the peroxisomal membrane", "membrane otera", "otera and fujiki", "and fujiki 2012", "2012 but", "but their transport", "their transport appears", "transport appears to", "appears to be", "to be less", "be less efficient", "less efficient than", "efficient than monomeric", "than monomeric proteins", "proteins freitas", "freitas et al.", "2011 inferred", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in freitas", "in freitas et", "et al. 2015", "2015 reviewed", "reviewed in dias", "in dias et", "dias et al.", "al. 2016 .
in", "2016 .
in the", ".
in the cytosol", "cytosol receptor", "proteins pex5", "pex5 and pex7", "pex7 bind", "bind to specific", "to specific sequence", "specific sequence motifs", "sequence motifs in", "motifs in cargo", "in cargo proteins", "proteins dodt", "dodt et al.", "1995 wiemer", "wiemer et al.", "1995 braverman", "braverman et al.", "et al. 1997", "al. 1997 .", "1997 . the", ". the long", "the long and", "long and short", "and short isoforms", "short isoforms of", "isoforms of pex5", "pex5 pex5l", "pex5l and pex5s", "pex5s bind", "bind peroxisome targeting", "peroxisome targeting sequence", "targeting sequence 1", "1 pts1", "pts1 originally", "originally identified in", "identified in firefly", "in firefly luciferase", "firefly luciferase by", "luciferase by gould", "by gould et", "gould et al.", "et al. 1989", "1989 found", "found on most", "on most peroxisomal", "most peroxisomal matrix", "peroxisomal matrix proteins", "proteins pex7", "pex7 binds pts2", "pts2 originally", "identified in rat", "in rat 3", "rat 3 ketoacyl", "3 ketoacyl coa", "ketoacyl coa thiolase", "coa thiolase by", "thiolase by swinkels", "by swinkels et", "swinkels et al.", "et al. 1991", "1991 found", "found on 3", "on 3 imported", "3 imported proteins", "imported proteins thus", "proteins thus far", "thus far in", "far in humans.", "in humans. the", "humans. the long", "the long isoform", "long isoform of", "isoform of pex5", "pex5l then", "then binds the", "binds the pex7:cargo", "the pex7:cargo protein", "pex7:cargo protein complex", "complex braverman", "et al. 1998", "1998 otera", "otera et al.", "et al. 2000", "al. 2000 .", "2000 . pex5s", ". pex5s l", "pex5s l bound", "l bound to", "bound to a", "to a cargo", "a cargo protein", "cargo protein or", "protein or pex5l", "or pex5l bound", "pex5l bound to", "bound to pex7:cargo", "to pex7:cargo protein", "pex7:cargo protein then", "protein then interacts", "then interacts with", "interacts with a", "with a complex", "a complex comprising", "complex comprising pex13", "pex13 pex14", "pex14 pex2", "pex2 pex10", "pex10 and", "and pex12 at", "pex12 at the", "at the peroxisomal", "membrane gould", "et al. 1996", "1996 fransen", "fransen et al.", "1998 inferred", "inferred from rat", "from rat homologs", "rat homologs in", "homologs in reguenga", "in reguenga et", "reguenga et al.", "et al. 2001", "al. 2001 .
the", "2001 .
the ensuing", ".
the ensuing step", "ensuing step in", "step in which", "in which the", "which the cargo", "the cargo protein", "cargo protein is", "protein is translocated", "is translocated across", "translocated across the", "across the membrane", "the membrane is", "membrane is not", "is not completely", "not completely understood.", "completely understood. during", "understood. during translocation", "translocation pex5", "and pex7 become", "pex7 become inserted", "become inserted into", "inserted into the", "into the membrane", "membrane wiemer", "1995 dodt", "1995 oliveira", "oliveira et al.", "et al. 2003", "2003 and", "and expose a", "expose a portion", "a portion of", "portion of their", "of their polypeptide", "their polypeptide chains", "polypeptide chains to", "chains to the", "to the organellar", "the organellar matrix", "matrix rodrigues", "rodrigues et al.", "al. 2015 .", "2015 . one", ". one current", "one current model", "current model envisages", "model envisages pex5", "envisages pex5 as", "pex5 as a", "as a plunger", "a plunger that", "plunger that inserts", "that inserts into", "inserts into a", "into a transmembrane", "a transmembrane barrel", "transmembrane barrel formed", "barrel formed by", "formed by pex14", "pex14 pex13", "pex13 pex2", "pex12 the", "the docking translocation", "docking translocation module", "al. 2017 .
after", "2017 .
after delivering", ".
after delivering cargo", "delivering cargo to", "cargo to the", "to the matrix", "matrix pex5", "and pex7 are", "pex7 are recycled", "are recycled back", "recycled back to", "back to the", "to the cytosol", "by a process", "a process requiring", "process requiring mono", "requiring mono ubiquitination", "mono ubiquitination of", "ubiquitination of pex5", "of pex5 and", "pex5 and atp", "and atp hydrolysis", "hydrolysis imanaka", "imanaka et al.", "et al. 1987", "1987 thoms", "thoms and erdmann", "and erdmann 2006", "2006 carvalho", "carvalho et al.", "et al. 2007", "al. 2007 .", "2007 . pex7", ". pex7 is", "pex7 is not", "is not ubiquitinated", "not ubiquitinated but", "ubiquitinated but its", "but its recycling", "its recycling requires", "recycling requires pex5", "requires pex5 mono", "pex5 mono ubiquitination.", "mono ubiquitination. a", "ubiquitination. a subcomplex", "a subcomplex of", "subcomplex of the", "of the docking", "translocation module comprising", "module comprising the", "comprising the ring", "the ring finger", "ring finger proteins", "finger proteins pex2", "and pex12 conjugates", "pex12 conjugates a", "conjugates a single", "a single ubiquitin", "single ubiquitin to", "ubiquitin to a", "to a cysteine", "a cysteine residue", "cysteine residue of", "residue of pex5", "pex5 carvalho", "2007 reviewed", "reviewed in platta", "in platta et", "platta et al.", "2016 . the", ". the mono", "the mono ubiquitinated", "mono ubiquitinated pex5", "ubiquitinated pex5 and", "pex5 and associated", "and associated pex7", "associated pex7 are", "pex7 are then", "are then extracted", "then extracted by", "extracted by the", "by the exportomer", "the exportomer complex", "exportomer complex consisting", "complex consisting of", "consisting of pex1", "pex1 pex6", "pex6 pex26", "pex26 and", "zfand6 inferred", "homologs in miyata", "in miyata et", "miyata et al.", "et al. 2012", "al. 2012 .", "2012 . pex1", ". pex1 and", "pex1 and pex6", "and pex6 are", "pex6 are members", "are members of", "members of the", "of the atpases", "the atpases associated", "atpases associated with", "associated with diverse", "with diverse cellular", "diverse cellular activities", "activities aaa", "aaa family", "family a", "a group of", "group of proteins", "of proteins that", "proteins that use", "that use the", "use the energy", "the energy of", "energy of atp", "of atp hydrolysis", "atp hydrolysis to", "hydrolysis to remodel", "to remodel molecular", "remodel molecular complexes.", "molecular complexes. pex1", "complexes. pex1 and", "and pex6 form", "pex6 form a", "form a hetero", "a hetero hexameric", "hetero hexameric ring", "ring best", "best described as", "described as a", "as a trimer", "a trimer of", "trimer of pex1/pex6", "of pex1/pex6 dimers", "dimers inferred", "inferred from yeast", "from yeast in", "yeast in platta", "et al. 2005", "2005 yeast", "yeast homologs reviewed", "homologs reviewed in", "reviewed in schwerter", "in schwerter et", "schwerter et al.", "2017 . data", ". data on", "data on the", "on the yeast", "the yeast pex1:pex6", "yeast pex1:pex6 complex", "pex1:pex6 complex suggest", "complex suggest that", "suggest that these", "that these atpases", "these atpases use", "atpases use a", "use a substrate", "a substrate threading", "substrate threading mechanism", "threading mechanism to", "mechanism to disrupt", "to disrupt protein", "disrupt protein protein", "protein protein interactions", "interactions gardner", "gardner et al.", "et al. 2018", "al. 2018 .", "2018 . pex7", "pex7 is also", "is also then", "also then returned", "then returned to", "returned to the", "cytosol rodrigues", "al. 2014 .", "2014 . once", ". once in", "once in the", "in the cytosol", "cytosol ubiquitinated", "ubiquitinated pex5 is", "pex5 is enzymatically", "is enzymatically deubiquitinated", "enzymatically deubiquitinated by", "deubiquitinated by usp9x", "by usp9x and", "usp9x and may", "and may also", "may also be", "also be non", "be non enzymatically", "non enzymatically deubiquitinated", "deubiquitinated by nucleophilic", "by nucleophilic attack", "nucleophilic attack of", "attack of the", "of the thioester", "the thioester bond", "thioester bond between", "bond between ubiquitin", "between ubiquitin and", "ubiquitin and the", "and the cysteine", "the cysteine residue", "of pex5 by", "pex5 by small", "by small metabolites", "small metabolites such", "metabolites such as", "such as glutathione", "glutathione grou", "grou et al.", "al. 2012 .
defects", "2012 .
defects in", ".
defects in peroxisomal", "in peroxisomal import", "peroxisomal import cause", "import cause human", "cause human diseases:", "human diseases: zellweger", "diseases: zellweger syndrome", "syndrome neonatal", "adrenoleukodystrophy infantile", "infantile refsum disease", "refsum disease and", "disease and rhizomelic", "and rhizomelic chondrodysplasia", "rhizomelic chondrodysplasia punctata", "chondrodysplasia punctata types", "punctata types 1", "types 1 and", "1 and 5", "5 bar\u00f8y", "bar\u00f8y et al.", "reviewed in nagotu", "in nagotu et", "nagotu et al.", "2012 braverman", "et al. 2013", "2013 wanders", "2014 fujiki", "2016 waterham", "waterham et al.", "peroxisomes are small cellular", "are small cellular organelles", "small cellular organelles that", "cellular organelles that are", "organelles that are bounded", "that are bounded by", "are bounded by a", "bounded by a single", "by a single membrane", "a single membrane and", "single membrane and contain", "membrane and contain variable", "and contain variable compositions", "contain variable compositions of", "variable compositions of proteins", "compositions of proteins depending", "of proteins depending on", "proteins depending on cell", "depending on cell type.", "on cell type. peroxisomes", "cell type. peroxisomes function", "type. peroxisomes function in", "peroxisomes function in oxidation", "function in oxidation of", "in oxidation of fatty", "oxidation of fatty acids", "fatty acids detoxification", "acids detoxification of", "of glyoxylate and", "glyoxylate and synthesis", "and synthesis of plasmalogens", "of plasmalogens glycerophospholipids", "plasmalogens glycerophospholipids containing", "glycerophospholipids containing an alcohol", "containing an alcohol with", "an alcohol with a", "alcohol with a vinyl", "with a vinyl ether", "a vinyl ether bond", "ether bond reviewed", "bond reviewed in", "reviewed in lohdi and", "in lohdi and semenkovich", "lohdi and semenkovich 2014", "and semenkovich 2014 .", "semenkovich 2014 . all", "2014 . all of", ". all of the", "all of the approximately", "of the approximately 46", "the approximately 46 proteins", "approximately 46 proteins contained", "46 proteins contained in", "proteins contained in peroxisomal", "contained in peroxisomal matrix", "in peroxisomal matrix are", "peroxisomal matrix are imported", "matrix are imported from", "are imported from the", "imported from the cytosol", "from the cytosol by", "the cytosol by a", "cytosol by a unique", "by a unique mechanism", "a unique mechanism that", "unique mechanism that does", "mechanism that does not", "that does not require", "does not require the", "not require the imported", "require the imported proteins", "the imported proteins to", "imported proteins to be", "proteins to be unfolded", "to be unfolded as", "be unfolded as they", "unfolded as they cross", "as they cross the", "they cross the membrane", "the membrane walton", "membrane walton et", "walton et al. 1995", "al. 1995 reviewed", "1995 reviewed in", "reviewed in ma et", "in ma et al.", "ma et al. 2011", "al. 2011 fujiki", "2011 fujiki et", "fujiki et al. 2014", "al. 2014 baker", "2014 baker et", "baker et al. 2016", "al. 2016 dias", "2016 dias et", "dias et al 2016", "al 2016 emmanoulidis", "2016 emmanoulidis et", "emmanoulidis et al. 2016", "al. 2016 erdmann", "2016 erdmann 2016", "erdmann 2016 francisco", "2016 francisco et", "francisco et al. 2017", "et al. 2017 .", "al. 2017 . the", "2017 . the incompletely", ". the incompletely characterized", "the incompletely characterized process", "incompletely characterized process appears", "characterized process appears to", "process appears to involve", "appears to involve the", "to involve the transport", "involve the transport of", "the transport of the", "transport of the proteins", "of the proteins through", "the proteins through a", "proteins through a variably", "through a variably sized", "a variably sized pore", "variably sized pore in", "sized pore in the", "pore in the membrane", "in the membrane comprising", "the membrane comprising at", "membrane comprising at least", "comprising at least pex5", "at least pex5 and", "least pex5 and pex14", "and pex14 inferred", "pex14 inferred from", "inferred from the yeast", "from the yeast homologs", "the yeast homologs in", "yeast homologs in meinecke", "homologs in meinecke et", "in meinecke et al.", "meinecke et al. 2010", "al. 2010 the", "2010 the yeast", "the yeast pore is", "yeast pore is reviewed", "pore is reviewed in", "is reviewed in meinecke", "reviewed in meinecke et", "meinecke et al. 2016", "et al. 2016 .", "al. 2016 . oligomeric", "2016 . oligomeric proteins", ". oligomeric proteins are", "oligomeric proteins are also", "proteins are also observed", "are also observed to", "also observed to cross", "observed to cross the", "to cross the peroxisomal", "cross the peroxisomal membrane", "peroxisomal membrane otera", "membrane otera and", "otera and fujiki 2012", "fujiki 2012 but", "2012 but their", "but their transport appears", "their transport appears to", "transport appears to be", "appears to be less", "to be less efficient", "be less efficient than", "less efficient than monomeric", "efficient than monomeric proteins", "monomeric proteins freitas", "proteins freitas et", "freitas et al. 2011", "al. 2011 inferred", "2011 inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in freitas", "homologs in freitas et", "in freitas et al.", "freitas et al. 2015", "al. 2015 reviewed", "2015 reviewed in", "reviewed in dias et", "in dias et al.", "dias et al. 2016", "et al. 2016 .
in", "al. 2016 .
in the", "2016 .
in the cytosol", "the cytosol receptor", "cytosol receptor proteins", "receptor proteins pex5", "proteins pex5 and", "and pex7 bind", "pex7 bind to", "bind to specific sequence", "to specific sequence motifs", "specific sequence motifs in", "sequence motifs in cargo", "motifs in cargo proteins", "cargo proteins dodt", "proteins dodt et", "dodt et al. 1995", "al. 1995 wiemer", "1995 wiemer et", "wiemer et al. 1995", "al. 1995 braverman", "1995 braverman et", "braverman et al. 1997", "et al. 1997 .", "al. 1997 . the", "1997 . the long", ". the long and", "the long and short", "long and short isoforms", "and short isoforms of", "short isoforms of pex5", "of pex5 pex5l", "pex5 pex5l and", "and pex5s bind", "pex5s bind peroxisome", "bind peroxisome targeting sequence", "peroxisome targeting sequence 1", "sequence 1 pts1", "pts1 originally identified", "originally identified in firefly", "identified in firefly luciferase", "in firefly luciferase by", "firefly luciferase by gould", "luciferase by gould et", "by gould et al.", "gould et al. 1989", "al. 1989 found", "1989 found on", "found on most peroxisomal", "on most peroxisomal matrix", "most peroxisomal matrix proteins", "matrix proteins pex7", "proteins pex7 binds", "binds pts2 originally", "pts2 originally identified", "originally identified in rat", "identified in rat 3", "in rat 3 ketoacyl", "rat 3 ketoacyl coa", "3 ketoacyl coa thiolase", "ketoacyl coa thiolase by", "coa thiolase by swinkels", "thiolase by swinkels et", "by swinkels et al.", "swinkels et al. 1991", "al. 1991 found", "1991 found on", "found on 3 imported", "on 3 imported proteins", "3 imported proteins thus", "imported proteins thus far", "proteins thus far in", "thus far in humans.", "far in humans. the", "in humans. the long", "humans. the long isoform", "the long isoform of", "long isoform of pex5", "pex5l then binds", "then binds the pex7:cargo", "binds the pex7:cargo protein", "the pex7:cargo protein complex", "protein complex braverman", "complex braverman et", "braverman et al. 1998", "al. 1998 otera", "1998 otera et", "otera et al. 2000", "et al. 2000 .", "al. 2000 . pex5s", "2000 . pex5s l", ". pex5s l bound", "pex5s l bound to", "l bound to a", "bound to a cargo", "to a cargo protein", "a cargo protein or", "cargo protein or pex5l", "protein or pex5l bound", "or pex5l bound to", "pex5l bound to pex7:cargo", "bound to pex7:cargo protein", "to pex7:cargo protein then", "pex7:cargo protein then interacts", "protein then interacts with", "then interacts with a", "interacts with a complex", "with a complex comprising", "a complex comprising pex13", "comprising pex13 pex14", "pex10 and pex12", "and pex12 at the", "pex12 at the peroxisomal", "at the peroxisomal membrane", "peroxisomal membrane gould", "membrane gould et", "gould et al. 1996", "al. 1996 fransen", "1996 fransen et", "fransen et al. 1998", "al. 1998 inferred", "1998 inferred from", "inferred from rat homologs", "from rat homologs in", "rat homologs in reguenga", "homologs in reguenga et", "in reguenga et al.", "reguenga et al. 2001", "et al. 2001 .
the", "al. 2001 .
the ensuing", "2001 .
the ensuing step", ".
the ensuing step in", "ensuing step in which", "step in which the", "in which the cargo", "which the cargo protein", "the cargo protein is", "cargo protein is translocated", "protein is translocated across", "is translocated across the", "translocated across the membrane", "across the membrane is", "the membrane is not", "membrane is not completely", "is not completely understood.", "not completely understood. during", "completely understood. during translocation", "during translocation pex5", "translocation pex5 and", "pex5 and pex7 become", "and pex7 become inserted", "pex7 become inserted into", "become inserted into the", "inserted into the membrane", "the membrane wiemer", "membrane wiemer et", "al. 1995 dodt", "1995 dodt et", "al. 1995 oliveira", "1995 oliveira et", "oliveira et al. 2003", "al. 2003 and", "2003 and expose", "and expose a portion", "expose a portion of", "a portion of their", "portion of their polypeptide", "of their polypeptide chains", "their polypeptide chains to", "polypeptide chains to the", "chains to the organellar", "to the organellar matrix", "organellar matrix rodrigues", "matrix rodrigues et", "rodrigues et al. 2015", "et al. 2015 .", "al. 2015 . one", "2015 . one current", ". one current model", "one current model envisages", "current model envisages pex5", "model envisages pex5 as", "envisages pex5 as a", "pex5 as a plunger", "as a plunger that", "a plunger that inserts", "plunger that inserts into", "that inserts into a", "inserts into a transmembrane", "into a transmembrane barrel", "a transmembrane barrel formed", "transmembrane barrel formed by", "barrel formed by pex14", "by pex14 pex13", "and pex12 the", "pex12 the docking", "the docking translocation module", "module francisco", "et al. 2017 .
after", "al. 2017 .
after delivering", "2017 .
after delivering cargo", ".
after delivering cargo to", "delivering cargo to the", "cargo to the matrix", "the matrix pex5", "matrix pex5 and", "pex5 and pex7 are", "and pex7 are recycled", "pex7 are recycled back", "are recycled back to", "recycled back to the", "back to the cytosol", "to the cytosol by", "cytosol by a process", "by a process requiring", "a process requiring mono", "process requiring mono ubiquitination", "requiring mono ubiquitination of", "mono ubiquitination of pex5", "ubiquitination of pex5 and", "of pex5 and atp", "pex5 and atp hydrolysis", "atp hydrolysis imanaka", "hydrolysis imanaka et", "imanaka et al. 1987", "al. 1987 thoms", "1987 thoms and", "thoms and erdmann 2006", "erdmann 2006 carvalho", "2006 carvalho et", "carvalho et al. 2007", "et al. 2007 .", "al. 2007 . pex7", "2007 . pex7 is", ". pex7 is not", "pex7 is not ubiquitinated", "is not ubiquitinated but", "not ubiquitinated but its", "ubiquitinated but its recycling", "but its recycling requires", "its recycling requires pex5", "recycling requires pex5 mono", "requires pex5 mono ubiquitination.", "pex5 mono ubiquitination. a", "mono ubiquitination. a subcomplex", "ubiquitination. a subcomplex of", "a subcomplex of the", "subcomplex of the docking", "of the docking translocation", "docking translocation module comprising", "translocation module comprising the", "module comprising the ring", "comprising the ring finger", "the ring finger proteins", "ring finger proteins pex2", "proteins pex2 pex10", "and pex12 conjugates a", "pex12 conjugates a single", "conjugates a single ubiquitin", "a single ubiquitin to", "single ubiquitin to a", "ubiquitin to a cysteine", "to a cysteine residue", "a cysteine residue of", "cysteine residue of pex5", "of pex5 carvalho", "pex5 carvalho et", "al. 2007 reviewed", "2007 reviewed in", "reviewed in platta et", "in platta et al.", "platta et al. 2016", "al. 2016 . the", "2016 . the mono", ". the mono ubiquitinated", "the mono ubiquitinated pex5", "mono ubiquitinated pex5 and", "ubiquitinated pex5 and associated", "pex5 and associated pex7", "and associated pex7 are", "associated pex7 are then", "pex7 are then extracted", "are then extracted by", "then extracted by the", "extracted by the exportomer", "by the exportomer complex", "the exportomer complex consisting", "exportomer complex consisting of", "complex consisting of pex1", "of pex1 pex6", "pex26 and zfand6", "and zfand6 inferred", "zfand6 inferred from", "rat homologs in miyata", "homologs in miyata et", "in miyata et al.", "miyata et al. 2012", "et al. 2012 .", "al. 2012 . pex1", "2012 . pex1 and", ". pex1 and pex6", "pex1 and pex6 are", "and pex6 are members", "pex6 are members of", "are members of the", "members of the atpases", "of the atpases associated", "the atpases associated with", "atpases associated with diverse", "associated with diverse cellular", "with diverse cellular activities", "cellular activities aaa", "family a group", "a group of proteins", "group of proteins that", "of proteins that use", "proteins that use the", "that use the energy", "use the energy of", "the energy of atp", "energy of atp hydrolysis", "of atp hydrolysis to", "atp hydrolysis to remodel", "hydrolysis to remodel molecular", "to remodel molecular complexes.", "remodel molecular complexes. pex1", "molecular complexes. pex1 and", "complexes. pex1 and pex6", "pex1 and pex6 form", "and pex6 form a", "pex6 form a hetero", "form a hetero hexameric", "a hetero hexameric ring", "hexameric ring best", "ring best described", "best described as a", "described as a trimer", "as a trimer of", "a trimer of pex1/pex6", "trimer of pex1/pex6 dimers", "pex1/pex6 dimers inferred", "dimers inferred from", "inferred from yeast in", "from yeast in platta", "yeast in platta et", "platta et al. 2005", "al. 2005 yeast", "2005 yeast homologs", "yeast homologs reviewed in", "homologs reviewed in schwerter", "reviewed in schwerter et", "in schwerter et al.", "schwerter et al. 2017", "al. 2017 . data", "2017 . data on", ". data on the", "data on the yeast", "on the yeast pex1:pex6", "the yeast pex1:pex6 complex", "yeast pex1:pex6 complex suggest", "pex1:pex6 complex suggest that", "complex suggest that these", "suggest that these atpases", "that these atpases use", "these atpases use a", "atpases use a substrate", "use a substrate threading", "a substrate threading mechanism", "substrate threading mechanism to", "threading mechanism to disrupt", "mechanism to disrupt protein", "to disrupt protein protein", "disrupt protein protein interactions", "protein interactions gardner", "interactions gardner et", "gardner et al. 2018", "et al. 2018 .", "al. 2018 . pex7", "2018 . pex7 is", ". pex7 is also", "pex7 is also then", "is also then returned", "also then returned to", "then returned to the", "returned to the cytosol", "the cytosol rodrigues", "cytosol rodrigues et", "rodrigues et al. 2014", "et al. 2014 .", "al. 2014 . once", "2014 . once in", ". once in the", "once in the cytosol", "the cytosol ubiquitinated", "cytosol ubiquitinated pex5", "ubiquitinated pex5 is enzymatically", "pex5 is enzymatically deubiquitinated", "is enzymatically deubiquitinated by", "enzymatically deubiquitinated by usp9x", "deubiquitinated by usp9x and", "by usp9x and may", "usp9x and may also", "and may also be", "may also be non", "also be non enzymatically", "be non enzymatically deubiquitinated", "non enzymatically deubiquitinated by", "enzymatically deubiquitinated by nucleophilic", "deubiquitinated by nucleophilic attack", "by nucleophilic attack of", "nucleophilic attack of the", "attack of the thioester", "of the thioester bond", "the thioester bond between", "thioester bond between ubiquitin", "bond between ubiquitin and", "between ubiquitin and the", "ubiquitin and the cysteine", "and the cysteine residue", "the cysteine residue of", "residue of pex5 by", "of pex5 by small", "pex5 by small metabolites", "by small metabolites such", "small metabolites such as", "metabolites such as glutathione", "as glutathione grou", "glutathione grou et", "grou et al. 2012", "et al. 2012 .
defects", "al. 2012 .
defects in", "2012 .
defects in peroxisomal", ".
defects in peroxisomal import", "in peroxisomal import cause", "peroxisomal import cause human", "import cause human diseases:", "cause human diseases: zellweger", "human diseases: zellweger syndrome", "zellweger syndrome neonatal", "syndrome neonatal adrenoleukodystrophy", "neonatal adrenoleukodystrophy infantile", "adrenoleukodystrophy infantile refsum", "infantile refsum disease and", "refsum disease and rhizomelic", "disease and rhizomelic chondrodysplasia", "and rhizomelic chondrodysplasia punctata", "rhizomelic chondrodysplasia punctata types", "chondrodysplasia punctata types 1", "punctata types 1 and", "types 1 and 5", "and 5 bar\u00f8y", "5 bar\u00f8y et", "bar\u00f8y et al. 2015", "reviewed in nagotu et", "in nagotu et al.", "nagotu et al. 2012", "al. 2012 braverman", "2012 braverman et", "braverman et al. 2013", "al. 2013 wanders", "2013 wanders 2014", "wanders 2014 fujiki", "2014 fujiki 2016", "fujiki 2016 waterham", "2016 waterham et", "waterham et al. 2016", "peroxisomes are small cellular organelles", "are small cellular organelles that", "small cellular organelles that are", "cellular organelles that are bounded", "organelles that are bounded by", "that are bounded by a", "are bounded by a single", "bounded by a single membrane", "by a single membrane and", "a single membrane and contain", "single membrane and contain variable", "membrane and contain variable compositions", "and contain variable compositions of", "contain variable compositions of proteins", "variable compositions of proteins depending", "compositions of proteins depending on", "of proteins depending on cell", "proteins depending on cell type.", "depending on cell type. peroxisomes", "on cell type. peroxisomes function", "cell type. peroxisomes function in", "type. peroxisomes function in oxidation", "peroxisomes function in oxidation of", "function in oxidation of fatty", "in oxidation of fatty acids", "of fatty acids detoxification", "fatty acids detoxification of", "acids detoxification of glyoxylate", "detoxification of glyoxylate and", "of glyoxylate and synthesis", "glyoxylate and synthesis of", "synthesis of plasmalogens glycerophospholipids", "of plasmalogens glycerophospholipids containing", "plasmalogens glycerophospholipids containing an", "glycerophospholipids containing an alcohol with", "containing an alcohol with a", "an alcohol with a vinyl", "alcohol with a vinyl ether", "with a vinyl ether bond", "vinyl ether bond reviewed", "ether bond reviewed in", "bond reviewed in lohdi", "reviewed in lohdi and semenkovich", "in lohdi and semenkovich 2014", "lohdi and semenkovich 2014 .", "and semenkovich 2014 . all", "semenkovich 2014 . all of", "2014 . all of the", ". all of the approximately", "all of the approximately 46", "of the approximately 46 proteins", "the approximately 46 proteins contained", "approximately 46 proteins contained in", "46 proteins contained in peroxisomal", "proteins contained in peroxisomal matrix", "contained in peroxisomal matrix are", "in peroxisomal matrix are imported", "peroxisomal matrix are imported from", "matrix are imported from the", "are imported from the cytosol", "imported from the cytosol by", "from the cytosol by a", "the cytosol by a unique", "cytosol by a unique mechanism", "by a unique mechanism that", "a unique mechanism that does", "unique mechanism that does not", "mechanism that does not require", "that does not require the", "does not require the imported", "not require the imported proteins", "require the imported proteins to", "the imported proteins to be", "imported proteins to be unfolded", "proteins to be unfolded as", "to be unfolded as they", "be unfolded as they cross", "unfolded as they cross the", "as they cross the membrane", "cross the membrane walton", "the membrane walton et", "membrane walton et al.", "et al. 1995 reviewed", "al. 1995 reviewed in", "1995 reviewed in ma", "reviewed in ma et al.", "in ma et al. 2011", "et al. 2011 fujiki", "al. 2011 fujiki et", "2011 fujiki et al.", "et al. 2014 baker", "al. 2014 baker et", "2014 baker et al.", "et al. 2016 dias", "al. 2016 dias et", "2016 dias et al", "et al 2016 emmanoulidis", "al 2016 emmanoulidis et", "2016 emmanoulidis et al.", "et al. 2016 erdmann", "al. 2016 erdmann 2016", "erdmann 2016 francisco et", "2016 francisco et al.", "francisco et al. 2017 .", "et al. 2017 . the", "al. 2017 . the incompletely", "2017 . the incompletely characterized", ". the incompletely characterized process", "the incompletely characterized process appears", "incompletely characterized process appears to", "characterized process appears to involve", "process appears to involve the", "appears to involve the transport", "to involve the transport of", "involve the transport of the", "the transport of the proteins", "transport of the proteins through", "of the proteins through a", "the proteins through a variably", "proteins through a variably sized", "through a variably sized pore", "a variably sized pore in", "variably sized pore in the", "sized pore in the membrane", "pore in the membrane comprising", "in the membrane comprising at", "the membrane comprising at least", "membrane comprising at least pex5", "comprising at least pex5 and", "at least pex5 and pex14", "pex5 and pex14 inferred", "and pex14 inferred from", "pex14 inferred from the", "inferred from the yeast homologs", "from the yeast homologs in", "the yeast homologs in meinecke", "yeast homologs in meinecke et", "homologs in meinecke et al.", "in meinecke et al. 2010", "et al. 2010 the", "al. 2010 the yeast", "2010 the yeast pore", "the yeast pore is reviewed", "yeast pore is reviewed in", "pore is reviewed in meinecke", "is reviewed in meinecke et", "reviewed in meinecke et al.", "in meinecke et al. 2016", "meinecke et al. 2016 .", "et al. 2016 . oligomeric", "al. 2016 . oligomeric proteins", "2016 . oligomeric proteins are", ". oligomeric proteins are also", "oligomeric proteins are also observed", "proteins are also observed to", "are also observed to cross", "also observed to cross the", "observed to cross the peroxisomal", "to cross the peroxisomal membrane", "the peroxisomal membrane otera", "peroxisomal membrane otera and", "membrane otera and fujiki", "and fujiki 2012 but", "fujiki 2012 but their", "2012 but their transport", "but their transport appears to", "their transport appears to be", "transport appears to be less", "appears to be less efficient", "to be less efficient than", "be less efficient than monomeric", "less efficient than monomeric proteins", "than monomeric proteins freitas", "monomeric proteins freitas et", "proteins freitas et al.", "et al. 2011 inferred", "al. 2011 inferred from", "2011 inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in freitas", "mouse homologs in freitas et", "homologs in freitas et al.", "in freitas et al. 2015", "et al. 2015 reviewed", "al. 2015 reviewed in", "2015 reviewed in dias", "reviewed in dias et al.", "in dias et al. 2016", "dias et al. 2016 .
in", "et al. 2016 .
in the", "al. 2016 .
in the cytosol", ".
in the cytosol receptor", "the cytosol receptor proteins", "receptor proteins pex5 and", "proteins pex5 and pex7", "pex5 and pex7 bind", "and pex7 bind to", "pex7 bind to specific", "bind to specific sequence motifs", "to specific sequence motifs in", "specific sequence motifs in cargo", "sequence motifs in cargo proteins", "in cargo proteins dodt", "cargo proteins dodt et", "proteins dodt et al.", "et al. 1995 wiemer", "al. 1995 wiemer et", "1995 wiemer et al.", "et al. 1995 braverman", "al. 1995 braverman et", "1995 braverman et al.", "braverman et al. 1997 .", "et al. 1997 . the", "al. 1997 . the long", "1997 . the long and", ". the long and short", "the long and short isoforms", "long and short isoforms of", "and short isoforms of pex5", "isoforms of pex5 pex5l", "of pex5 pex5l and", "pex5 pex5l and pex5s", "pex5l and pex5s bind", "and pex5s bind peroxisome", "pex5s bind peroxisome targeting", "bind peroxisome targeting sequence 1", "targeting sequence 1 pts1", "1 pts1 originally", "pts1 originally identified in", "originally identified in firefly luciferase", "identified in firefly luciferase by", "in firefly luciferase by gould", "firefly luciferase by gould et", "luciferase by gould et al.", "by gould et al. 1989", "et al. 1989 found", "al. 1989 found on", "1989 found on most", "found on most peroxisomal matrix", "on most peroxisomal matrix proteins", "peroxisomal matrix proteins pex7", "matrix proteins pex7 binds", "proteins pex7 binds pts2", "pex7 binds pts2 originally", "binds pts2 originally identified", "pts2 originally identified in", "originally identified in rat 3", "identified in rat 3 ketoacyl", "in rat 3 ketoacyl coa", "rat 3 ketoacyl coa thiolase", "3 ketoacyl coa thiolase by", "ketoacyl coa thiolase by swinkels", "coa thiolase by swinkels et", "thiolase by swinkels et al.", "by swinkels et al. 1991", "et al. 1991 found", "al. 1991 found on", "1991 found on 3", "found on 3 imported proteins", "on 3 imported proteins thus", "3 imported proteins thus far", "imported proteins thus far in", "proteins thus far in humans.", "thus far in humans. the", "far in humans. the long", "in humans. the long isoform", "humans. the long isoform of", "the long isoform of pex5", "isoform of pex5 pex5l", "pex5 pex5l then", "pex5l then binds the", "then binds the pex7:cargo protein", "binds the pex7:cargo protein complex", "pex7:cargo protein complex braverman", "protein complex braverman et", "complex braverman et al.", "et al. 1998 otera", "al. 1998 otera et", "1998 otera et al.", "otera et al. 2000 .", "et al. 2000 . pex5s", "al. 2000 . pex5s l", "2000 . pex5s l bound", ". pex5s l bound to", "pex5s l bound to a", "l bound to a cargo", "bound to a cargo protein", "to a cargo protein or", "a cargo protein or pex5l", "cargo protein or pex5l bound", "protein or pex5l bound to", "or pex5l bound to pex7:cargo", "pex5l bound to pex7:cargo protein", "bound to pex7:cargo protein then", "to pex7:cargo protein then interacts", "pex7:cargo protein then interacts with", "protein then interacts with a", "then interacts with a complex", "interacts with a complex comprising", "with a complex comprising pex13", "complex comprising pex13 pex14", "pex13 pex14 pex2", "pex14 pex2 pex10", "pex2 pex10 and", "pex10 and pex12 at", "and pex12 at the peroxisomal", "pex12 at the peroxisomal membrane", "the peroxisomal membrane gould", "peroxisomal membrane gould et", "membrane gould et al.", "et al. 1996 fransen", "al. 1996 fransen et", "1996 fransen et al.", "et al. 1998 inferred", "al. 1998 inferred from", "1998 inferred from rat", "inferred from rat homologs in", "from rat homologs in reguenga", "rat homologs in reguenga et", "homologs in reguenga et al.", "in reguenga et al. 2001", "reguenga et al. 2001 .
the", "et al. 2001 .
the ensuing", "al. 2001 .
the ensuing step", "2001 .
the ensuing step in", ".
the ensuing step in which", "ensuing step in which the", "step in which the cargo", "in which the cargo protein", "which the cargo protein is", "the cargo protein is translocated", "cargo protein is translocated across", "protein is translocated across the", "is translocated across the membrane", "translocated across the membrane is", "across the membrane is not", "the membrane is not completely", "membrane is not completely understood.", "is not completely understood. during", "not completely understood. during translocation", "understood. during translocation pex5", "during translocation pex5 and", "translocation pex5 and pex7", "pex5 and pex7 become inserted", "and pex7 become inserted into", "pex7 become inserted into the", "become inserted into the membrane", "into the membrane wiemer", "the membrane wiemer et", "membrane wiemer et al.", "et al. 1995 dodt", "al. 1995 dodt et", "1995 dodt et al.", "et al. 1995 oliveira", "al. 1995 oliveira et", "1995 oliveira et al.", "et al. 2003 and", "al. 2003 and expose", "2003 and expose a", "and expose a portion of", "expose a portion of their", "a portion of their polypeptide", "portion of their polypeptide chains", "of their polypeptide chains to", "their polypeptide chains to the", "polypeptide chains to the organellar", "chains to the organellar matrix", "the organellar matrix rodrigues", "organellar matrix rodrigues et", "matrix rodrigues et al.", "rodrigues et al. 2015 .", "et al. 2015 . one", "al. 2015 . one current", "2015 . one current model", ". one current model envisages", "one current model envisages pex5", "current model envisages pex5 as", "model envisages pex5 as a", "envisages pex5 as a plunger", "pex5 as a plunger that", "as a plunger that inserts", "a plunger that inserts into", "plunger that inserts into a", "that inserts into a transmembrane", "inserts into a transmembrane barrel", "into a transmembrane barrel formed", "a transmembrane barrel formed by", "transmembrane barrel formed by pex14", "formed by pex14 pex13", "pex14 pex13 pex2", "pex13 pex2 pex10", "and pex12 the docking", "pex12 the docking translocation", "translocation module francisco", "module francisco et", "francisco et al. 2017 .
after", "et al. 2017 .
after delivering", "al. 2017 .
after delivering cargo", "2017 .
after delivering cargo to", ".
after delivering cargo to the", "delivering cargo to the matrix", "to the matrix pex5", "the matrix pex5 and", "matrix pex5 and pex7", "pex5 and pex7 are recycled", "and pex7 are recycled back", "pex7 are recycled back to", "are recycled back to the", "recycled back to the cytosol", "back to the cytosol by", "to the cytosol by a", "the cytosol by a process", "cytosol by a process requiring", "by a process requiring mono", "a process requiring mono ubiquitination", "process requiring mono ubiquitination of", "requiring mono ubiquitination of pex5", "mono ubiquitination of pex5 and", "ubiquitination of pex5 and atp", "of pex5 and atp hydrolysis", "and atp hydrolysis imanaka", "atp hydrolysis imanaka et", "hydrolysis imanaka et al.", "et al. 1987 thoms", "al. 1987 thoms and", "1987 thoms and erdmann", "and erdmann 2006 carvalho", "erdmann 2006 carvalho et", "2006 carvalho et al.", "carvalho et al. 2007 .", "et al. 2007 . pex7", "al. 2007 . pex7 is", "2007 . pex7 is not", ". pex7 is not ubiquitinated", "pex7 is not ubiquitinated but", "is not ubiquitinated but its", "not ubiquitinated but its recycling", "ubiquitinated but its recycling requires", "but its recycling requires pex5", "its recycling requires pex5 mono", "recycling requires pex5 mono ubiquitination.", "requires pex5 mono ubiquitination. a", "pex5 mono ubiquitination. a subcomplex", "mono ubiquitination. a subcomplex of", "ubiquitination. a subcomplex of the", "a subcomplex of the docking", "subcomplex of the docking translocation", "of the docking translocation module", "the docking translocation module comprising", "docking translocation module comprising the", "translocation module comprising the ring", "module comprising the ring finger", "comprising the ring finger proteins", "the ring finger proteins pex2", "finger proteins pex2 pex10", "pex10 and pex12 conjugates", "and pex12 conjugates a single", "pex12 conjugates a single ubiquitin", "conjugates a single ubiquitin to", "a single ubiquitin to a", "single ubiquitin to a cysteine", "ubiquitin to a cysteine residue", "to a cysteine residue of", "a cysteine residue of pex5", "residue of pex5 carvalho", "of pex5 carvalho et", "pex5 carvalho et al.", "et al. 2007 reviewed", "al. 2007 reviewed in", "2007 reviewed in platta", "reviewed in platta et al.", "in platta et al. 2016", "platta et al. 2016 .", "et al. 2016 . the", "al. 2016 . the mono", "2016 . the mono ubiquitinated", ". the mono ubiquitinated pex5", "the mono ubiquitinated pex5 and", "mono ubiquitinated pex5 and associated", "ubiquitinated pex5 and associated pex7", "pex5 and associated pex7 are", "and associated pex7 are then", "associated pex7 are then extracted", "pex7 are then extracted by", "are then extracted by the", "then extracted by the exportomer", "extracted by the exportomer complex", "by the exportomer complex consisting", "the exportomer complex consisting of", "exportomer complex consisting of pex1", "consisting of pex1 pex6", "pex1 pex6 pex26", "pex6 pex26 and", "and zfand6 inferred from", "zfand6 inferred from rat", "from rat homologs in miyata", "rat homologs in miyata et", "homologs in miyata et al.", "in miyata et al. 2012", "miyata et al. 2012 .", "et al. 2012 . pex1", "al. 2012 . pex1 and", "2012 . pex1 and pex6", ". pex1 and pex6 are", "pex1 and pex6 are members", "and pex6 are members of", "pex6 are members of the", "are members of the atpases", "members of the atpases associated", "of the atpases associated with", "the atpases associated with diverse", "atpases associated with diverse cellular", "associated with diverse cellular activities", "diverse cellular activities aaa", "activities aaa family", "aaa family a", "family a group of", "a group of proteins that", "group of proteins that use", "of proteins that use the", "proteins that use the energy", "that use the energy of", "use the energy of atp", "the energy of atp hydrolysis", "energy of atp hydrolysis to", "of atp hydrolysis to remodel", "atp hydrolysis to remodel molecular", "hydrolysis to remodel molecular complexes.", "to remodel molecular complexes. pex1", "remodel molecular complexes. pex1 and", "molecular complexes. pex1 and pex6", "complexes. pex1 and pex6 form", "pex1 and pex6 form a", "and pex6 form a hetero", "pex6 form a hetero hexameric", "form a hetero hexameric ring", "hetero hexameric ring best", "hexameric ring best described", "ring best described as", "best described as a trimer", "described as a trimer of", "as a trimer of pex1/pex6", "a trimer of pex1/pex6 dimers", "of pex1/pex6 dimers inferred", "pex1/pex6 dimers inferred from", "dimers inferred from yeast", "inferred from yeast in platta", "from yeast in platta et", "yeast in platta et al.", "in platta et al. 2005", "et al. 2005 yeast", "al. 2005 yeast homologs", "2005 yeast homologs reviewed", "yeast homologs reviewed in schwerter", "homologs reviewed in schwerter et", "reviewed in schwerter et al.", "in schwerter et al. 2017", "schwerter et al. 2017 .", "et al. 2017 . data", "al. 2017 . data on", "2017 . data on the", ". data on the yeast", "data on the yeast pex1:pex6", "on the yeast pex1:pex6 complex", "the yeast pex1:pex6 complex suggest", "yeast pex1:pex6 complex suggest that", "pex1:pex6 complex suggest that these", "complex suggest that these atpases", "suggest that these atpases use", "that these atpases use a", "these atpases use a substrate", "atpases use a substrate threading", "use a substrate threading mechanism", "a substrate threading mechanism to", "substrate threading mechanism to disrupt", "threading mechanism to disrupt protein", "mechanism to disrupt protein protein", "to disrupt protein protein interactions", "protein protein interactions gardner", "protein interactions gardner et", "interactions gardner et al.", "gardner et al. 2018 .", "et al. 2018 . pex7", "al. 2018 . pex7 is", "2018 . pex7 is also", ". pex7 is also then", "pex7 is also then returned", "is also then returned to", "also then returned to the", "then returned to the cytosol", "to the cytosol rodrigues", "the cytosol rodrigues et", "cytosol rodrigues et al.", "rodrigues et al. 2014 .", "et al. 2014 . once", "al. 2014 . once in", "2014 . once in the", ". once in the cytosol", "in the cytosol ubiquitinated", "the cytosol ubiquitinated pex5", "cytosol ubiquitinated pex5 is", "ubiquitinated pex5 is enzymatically deubiquitinated", "pex5 is enzymatically deubiquitinated by", "is enzymatically deubiquitinated by usp9x", "enzymatically deubiquitinated by usp9x and", "deubiquitinated by usp9x and may", "by usp9x and may also", "usp9x and may also be", "and may also be non", "may also be non enzymatically", "also be non enzymatically deubiquitinated", "be non enzymatically deubiquitinated by", "non enzymatically deubiquitinated by nucleophilic", "enzymatically deubiquitinated by nucleophilic attack", "deubiquitinated by nucleophilic attack of", "by nucleophilic attack of the", "nucleophilic attack of the thioester", "attack of the thioester bond", "of the thioester bond between", "the thioester bond between ubiquitin", "thioester bond between ubiquitin and", "bond between ubiquitin and the", "between ubiquitin and the cysteine", "ubiquitin and the cysteine residue", "and the cysteine residue of", "the cysteine residue of pex5", "cysteine residue of pex5 by", "residue of pex5 by small", "of pex5 by small metabolites", "pex5 by small metabolites such", "by small metabolites such as", "small metabolites such as glutathione", "such as glutathione grou", "as glutathione grou et", "glutathione grou et al.", "grou et al. 2012 .
defects", "et al. 2012 .
defects in", "al. 2012 .
defects in peroxisomal", "2012 .
defects in peroxisomal import", ".
defects in peroxisomal import cause", "in peroxisomal import cause human", "peroxisomal import cause human diseases:", "import cause human diseases: zellweger", "cause human diseases: zellweger syndrome", "diseases: zellweger syndrome neonatal", "zellweger syndrome neonatal adrenoleukodystrophy", "neonatal adrenoleukodystrophy infantile refsum", "adrenoleukodystrophy infantile refsum disease", "infantile refsum disease and rhizomelic", "refsum disease and rhizomelic chondrodysplasia", "disease and rhizomelic chondrodysplasia punctata", "and rhizomelic chondrodysplasia punctata types", "rhizomelic chondrodysplasia punctata types 1", "chondrodysplasia punctata types 1 and", "punctata types 1 and 5", "1 and 5 bar\u00f8y", "and 5 bar\u00f8y et", "5 bar\u00f8y et al.", "2015 reviewed in nagotu", "reviewed in nagotu et al.", "in nagotu et al. 2012", "et al. 2012 braverman", "al. 2012 braverman et", "2012 braverman et al.", "et al. 2013 wanders", "al. 2013 wanders 2014", "wanders 2014 fujiki 2016", "fujiki 2016 waterham et", "2016 waterham et al.", "waterham et al. 2016 ." ] }, { "record_id": "GLY_000594_1_672", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9033500", "r hsa", "hsa 9033500", "r hsa 9033500" ] }, { "record_id": "GLY_000594_1_672", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tysnd1 cleaves", "cleaves peroxisomal", "peroxisomal proteins", "tysnd1 cleaves peroxisomal", "cleaves peroxisomal proteins", "tysnd1 cleaves peroxisomal proteins", "after proteins", "proteins are", "are imported", "imported into", "into the", "the peroxisome", "peroxisome a", "a subset", "subset of", "of proteins", "are cleaved", "cleaved by", "by the", "the protease", "protease tysnd1", "okumoto et", "et al.", "al. 2011", "2011 .", ". based", "based onmutagenesis", "onmutagenesis of", "of human", "human tysnd1", "and the", "the homolog", "homolog in", "in arabidopsis", "schuhmann et", "al. 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"GLY_000594_1_674", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "912446", "r hsa", "hsa 912446", "r hsa 912446" ] }, { "record_id": "GLY_000594_1_674", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "meiotic recombination", "recombination exchanges", "exchanges segments", "segments of", "of duplex", "duplex dna", "dna between", "between chromosomal", "chromosomal homologs", "generating genetic", "genetic diversity", "reviewed in", "in handel", "handel and", "and schimenti", "schimenti 2010", "inagaki et", "et al.", "al. 2010", "cohen et", "al. 2006", "2006 .", ". there", "there are", "are two", "two forms", "forms of", "of recombination:", "recombination: non", "non crossover", "and crossover", "co .", ". in", "in mammals", "the former", "former is", "is required", "required for", "for correct", "correct pairing", "pairing and", "and synapsis", "synapsis of", "of homologous", "homologous 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the", "2010.

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for review", "review please", "please refer to", "refer to cohen", "to cohen et", "2006 inagaki", "2010 handel", "and schimenti 2010.

the", "schimenti 2010.

the firrm:fignl1", "2010.

the firrm:fignl1 complex", "firrm:fignl1 complex has", "complex has recently", "has recently been", "recently been reported", "been reported to", "reported to interact", "to interact with", "interact with both", "with both rad51", "both rad51 and", "and dmc1 recombinases", "dmc1 recombinases and", "recombinases and limit", "and limit the", "limit the formation", "formation of meiotic", "of meiotic crossovers", "meiotic crossovers by", "crossovers by regulating", "by regulating rad51", "regulating rad51 and", "and dmc1 dynamics", "dmc1 dynamics during", "dynamics during meiosis", "meiosis fernandes", "fernandes et al.", "et al. 2018", "al. 2018 .", "meiotic recombination exchanges segments", "recombination exchanges segments of", "exchanges segments of duplex", "segments of duplex dna", "of duplex dna between", "duplex dna between chromosomal", "dna between chromosomal homologs", "chromosomal homologs generating", "homologs generating genetic", "genetic diversity reviewed", "diversity reviewed in", "reviewed in handel and", "in handel and schimenti", "handel and schimenti 2010", "schimenti 2010 inagaki", "2010 inagaki et", "inagaki et al. 2010", "al. 2010 cohen", "2010 cohen et", "cohen et al. 2006", "et al. 2006 .", "al. 2006 . there", "2006 . there are", ". there are two", "there are two forms", "are two forms of", "two forms of recombination:", "forms of recombination: non", "of recombination: non crossover", "non crossover nco", "nco and crossover", "and crossover co", "crossover co .", "co . in mammals", "in mammals the", "mammals the former", "the former is required", "former is required for", "is required for correct", "required for correct pairing", "for correct pairing and", "correct pairing and synapsis", "pairing and synapsis of", "and synapsis of homologous", "synapsis of homologous chromosomes", "homologous chromosomes while", "chromosomes while co", "while co intermediates called", "co intermediates called chiasmata", "intermediates called chiasmata are", "called chiasmata are required", "chiasmata are required for", "are required for correct", "required for correct segregation", "for correct segregation of", "correct segregation of bivalents.
meiotic", "segregation of bivalents.
meiotic recombination", "of bivalents.
meiotic recombination is", "bivalents.
meiotic recombination is initiated", "recombination is initiated by", "is initiated by double", "initiated by double strand", "by double strand breaks", "double strand breaks created", "strand breaks created by", "breaks created by spo11", "by spo11 which", "spo11 which remains", "which remains covalently attached", "remains covalently attached to", "covalently attached to the", "attached to the 5'", "to the 5' ends", "the 5' ends after", "5' ends after cleavage.", "ends after cleavage. spo11", "after cleavage. spo11 is", "cleavage. spo11 is removed", "spo11 is removed by", "is removed by cleavage", "removed by cleavage of", "by cleavage of single", "cleavage of single dna", "of single dna strands", "single dna strands adjacent", "dna strands adjacent to", "strands adjacent to the", "adjacent to the covalent", "to the covalent linkage.", "the covalent linkage. the", "covalent linkage. the resulting", "linkage. the resulting 5'", "the resulting 5' ends", "resulting 5' ends are", "5' ends are further", "ends are further resected", "are further resected to", "further resected to produce", "resected to produce protruding", "to produce protruding 3'", "produce protruding 3' ends.", "protruding 3' ends. the", "3' ends. the single", "ends. the single stranded", "the single stranded 3'", "single stranded 3' ends", "stranded 3' ends are", "3' ends are bound", "ends are bound by", "are bound by rad51", "bound by rad51 and", "by rad51 and dmc1", "and dmc1 homologs", "dmc1 homologs of", "homologs of reca that", "of reca that catalyze", "reca that catalyze a", "that catalyze a search", "catalyze a search for", "a search for homology", "search for homology between", "for homology between the", "homology between the bound", "between the bound single", "the bound single strand", "bound single strand and", "single strand and duplex", "strand and duplex dna", "and duplex dna of", "duplex dna of the", "dna of the chromosomal", "of the chromosomal homolog.", "the chromosomal homolog. rad51", "chromosomal homolog. rad51 and", "homolog. rad51 and dmc1", "rad51 and dmc1 then", "and dmc1 then catalyze", "dmc1 then catalyze the", "then catalyze the invasion", "catalyze the invasion of", "the invasion of the", "invasion of the single", "of the single strand", "the single strand into", "single strand into the", "strand into the homologous", "into the homologous duplex", "the homologous duplex and", "homologous duplex and the", "duplex and the formation", "and the formation of", "the formation of a", "formation of a d", "of a d loop", "a d loop heteroduplex.", "d loop heteroduplex. approximately", "loop heteroduplex. approximately 90%", "heteroduplex. approximately 90% of", "approximately 90% of heteroduplexes", "90% of heteroduplexes are", "of heteroduplexes are resolved", "heteroduplexes are resolved without", "are resolved without crossovers", "without crossovers nco", "nco probably", "probably by synthesis dependent", "by synthesis dependent strand", "synthesis dependent strand annealing.
the", "dependent strand annealing.
the invasive", "strand annealing.
the invasive strand", "annealing.
the invasive strand is", "invasive strand is extended", "strand is extended along", "is extended along the", "extended along the homolog", "along the homolog and", "the homolog and ligated", "homolog and ligated back", "and ligated back to", "ligated back to its", "back to its original", "to its original duplex", "original duplex creating", "duplex creating a", "creating a double holliday", "a double holliday junction.", "double holliday junction. the", "holliday junction. the mismatch", "junction. the mismatch repair", "the mismatch repair proteins", "mismatch repair proteins msh4", "proteins msh4 msh5", "msh4 msh5 participate", "msh5 participate in this", "participate in this process", "this process possibly", "process possibly by", "possibly by stabilizing the", "by stabilizing the duplexes.", "stabilizing the duplexes. the", "the duplexes. the mismatch", "duplexes. the mismatch repair", "mismatch repair proteins mlh1", "repair proteins mlh1 and", "proteins mlh1 and mlh3", "mlh1 and mlh3 are", "and mlh3 are then", "mlh3 are then recruited", "are then recruited to", "then recruited to the", "recruited to the double", "to the double holliday", "the double holliday structure", "double holliday structure and", "holliday structure and an", "structure and an unidentified", "and an unidentified resolvase", "unidentified resolvase mus81?", "resolvase mus81? gen1?", "mus81? gen1? cleaves", "gen1? cleaves the", "cleaves the junctions to", "the junctions to yield", "junctions to yield a", "to yield a crossover.", "yield a crossover.
crossovers", "a crossover.
crossovers are", "crossover.
crossovers are not", "
crossovers are not randomly", "are not randomly distributed:", "not randomly distributed: the", "randomly distributed: the histone", "distributed: the histone methyltransferase", "the histone methyltransferase prdm9", "histone methyltransferase prdm9 recruits", "methyltransferase prdm9 recruits the", "prdm9 recruits the recombination", "recruits the recombination machinery", "the recombination machinery to", "recombination machinery to genetically", "machinery to genetically determined", "to genetically determined hotspots", "genetically determined hotspots in", "determined hotspots in the", "hotspots in the genome", "in the genome and", "the genome and each", "genome and each incipient", "and each incipient crossover", "each incipient crossover somehow", "incipient crossover somehow inhibits", "crossover somehow inhibits formation", "somehow inhibits formation of", "inhibits formation of crossovers", "formation of crossovers nearby", "crossovers nearby a", "nearby a phenomenon", "a phenomenon called crossover", "phenomenon called crossover interference.", "called crossover interference. each", "crossover interference. each chromosome", "interference. each chromosome bivalent", "chromosome bivalent including", "bivalent including the", "including the x y", "the x y body", "x y body in", "y body in males", "in males has", "males has at", "has at least one", "at least one crossover", "least one crossover and", "one crossover and this", "crossover and this is", "and this is required", "this is required for", "is required for meiosis", "required for meiosis to", "for meiosis to proceed", "meiosis to proceed correctly.

for", "to proceed correctly.

for review", "correctly.

for review please", "review please refer", "please refer to cohen", "refer to cohen et", "to cohen et al.", "al. 2006 inagaki", "2006 inagaki et", "al. 2010 handel", "2010 handel and", "handel and schimenti 2010.

the", "and schimenti 2010.

the firrm:fignl1", "schimenti 2010.

the firrm:fignl1 complex", "2010.

the firrm:fignl1 complex has", "firrm:fignl1 complex has recently", "complex has recently been", "has recently been reported", "recently been reported to", "been reported to interact", "reported to interact with", "to interact with both", "interact with both rad51", "with both rad51 and", "both rad51 and dmc1", "rad51 and dmc1 recombinases", "and dmc1 recombinases and", "dmc1 recombinases and limit", "recombinases and limit the", "and limit the formation", "limit the formation of", "the formation of meiotic", "formation of meiotic crossovers", "of meiotic crossovers by", "meiotic crossovers by regulating", "crossovers by regulating rad51", "by regulating rad51 and", "regulating rad51 and dmc1", "rad51 and dmc1 dynamics", "and dmc1 dynamics during", "dmc1 dynamics during meiosis", "during meiosis fernandes", "meiosis fernandes et", "fernandes et al. 2018", "et al. 2018 .", "meiotic recombination exchanges segments of", "recombination exchanges segments of duplex", "exchanges segments of duplex dna", "segments of duplex dna between", "of duplex dna between chromosomal", "duplex dna between chromosomal homologs", "between chromosomal homologs generating", "chromosomal homologs generating genetic", "homologs generating genetic diversity", "generating genetic diversity reviewed", "genetic diversity reviewed in", "diversity reviewed in handel", "reviewed in handel and schimenti", "in handel and schimenti 2010", "and schimenti 2010 inagaki", "schimenti 2010 inagaki et", "2010 inagaki et al.", "et al. 2010 cohen", "al. 2010 cohen et", "2010 cohen et al.", "cohen et al. 2006 .", "et al. 2006 . there", "al. 2006 . there are", "2006 . there are two", ". there are two forms", "there are two forms of", "are two forms of recombination:", "two forms of recombination: non", "forms of recombination: non crossover", "recombination: non crossover nco", "crossover nco and", "and crossover co .", "crossover co . in", ". in mammals the", "in mammals the former", "mammals the former is", "the former is required for", "former is required for correct", "is required for correct pairing", "required for correct pairing and", "for correct pairing and synapsis", "correct pairing and synapsis of", "pairing and synapsis of homologous", "and synapsis of homologous chromosomes", "of homologous chromosomes while", "homologous chromosomes while co", "chromosomes while co intermediates", "while co intermediates called chiasmata", "co intermediates called chiasmata are", "intermediates called chiasmata are required", "called chiasmata are required for", "chiasmata are required for correct", "are required for correct segregation", "required for correct segregation of", "for correct segregation of bivalents.
meiotic", "correct segregation of bivalents.
meiotic recombination", "segregation of bivalents.
meiotic recombination is", "of bivalents.
meiotic recombination is initiated", "bivalents.
meiotic recombination is initiated by", "recombination is initiated by double", "is initiated by double strand", "initiated by double strand breaks", "by double strand breaks created", "double strand breaks created by", "strand breaks created by spo11", "created by spo11 which", "by spo11 which remains", "spo11 which remains covalently", "which remains covalently attached to", "remains covalently attached to the", "covalently attached to the 5'", "attached to the 5' ends", "to the 5' ends after", "the 5' ends after cleavage.", "5' ends after cleavage. spo11", "ends after cleavage. spo11 is", "after cleavage. spo11 is removed", "cleavage. spo11 is removed by", "spo11 is removed by cleavage", "is removed by cleavage of", "removed by cleavage of single", "by cleavage of single dna", "cleavage of single dna strands", "of single dna strands adjacent", "single dna strands adjacent to", "dna strands adjacent to the", "strands adjacent to the covalent", "adjacent to the covalent linkage.", "to the covalent linkage. the", "the covalent linkage. the resulting", "covalent linkage. the resulting 5'", "linkage. the resulting 5' ends", "the resulting 5' ends are", "resulting 5' ends are further", "5' ends are further resected", "ends are further resected to", "are further resected to produce", "further resected to produce protruding", "resected to produce protruding 3'", "to produce protruding 3' ends.", "produce protruding 3' ends. the", "protruding 3' ends. the single", "3' ends. the single stranded", "ends. the single stranded 3'", "the single stranded 3' ends", "single stranded 3' ends are", "stranded 3' ends are bound", "3' ends are bound by", "ends are bound by rad51", "are bound by rad51 and", "bound by rad51 and dmc1", "rad51 and dmc1 homologs", "and dmc1 homologs of", "dmc1 homologs of reca", "homologs of reca that catalyze", "of reca that catalyze a", "reca that catalyze a search", "that catalyze a search for", "catalyze a search for homology", "a search for homology between", "search for homology between the", "for homology between the bound", "homology between the bound single", "between the bound single strand", "the bound single strand and", "bound single strand and duplex", "single strand and duplex dna", "strand and duplex dna of", "and duplex dna of the", "duplex dna of the chromosomal", "dna of the chromosomal homolog.", "of the chromosomal homolog. rad51", "the chromosomal homolog. rad51 and", "chromosomal homolog. rad51 and dmc1", "homolog. rad51 and dmc1 then", "rad51 and dmc1 then catalyze", "and dmc1 then catalyze the", "dmc1 then catalyze the invasion", "then catalyze the invasion of", "catalyze the invasion of the", "the invasion of the single", "invasion of the single strand", "of the single strand into", "the single strand into the", "single strand into the homologous", "strand into the homologous duplex", "into the homologous duplex and", "the homologous duplex and the", "homologous duplex and the formation", "duplex and the formation of", "and the formation of a", "the formation of a d", "formation of a d loop", "of a d loop heteroduplex.", "a d loop heteroduplex. approximately", "d loop heteroduplex. approximately 90%", "loop heteroduplex. approximately 90% of", "heteroduplex. approximately 90% of heteroduplexes", "approximately 90% of heteroduplexes are", "90% of heteroduplexes are resolved", "of heteroduplexes are resolved without", "heteroduplexes are resolved without crossovers", "resolved without crossovers nco", "nco probably by", "probably by synthesis dependent strand", "by synthesis dependent strand annealing.
the", "synthesis dependent strand annealing.
the invasive", "dependent strand annealing.
the invasive strand", "strand annealing.
the invasive strand is", "annealing.
the invasive strand is extended", "invasive strand is extended along", "strand is extended along the", "is extended along the homolog", "extended along the homolog and", "along the homolog and ligated", "the homolog and ligated back", "homolog and ligated back to", "and ligated back to its", "ligated back to its original", "back to its original duplex", "its original duplex creating", "original duplex creating a", "duplex creating a double", "creating a double holliday junction.", "a double holliday junction. the", "double holliday junction. the mismatch", "holliday junction. the mismatch repair", "junction. the mismatch repair proteins", "the mismatch repair proteins msh4", "repair proteins msh4 msh5", "proteins msh4 msh5 participate", "msh4 msh5 participate in", "msh5 participate in this process", "in this process possibly", "this process possibly by", "process possibly by stabilizing", "possibly by stabilizing the duplexes.", "by stabilizing the duplexes. the", "stabilizing the duplexes. the mismatch", "the duplexes. the mismatch repair", "duplexes. the mismatch repair proteins", "the mismatch repair proteins mlh1", "mismatch repair proteins mlh1 and", "repair proteins mlh1 and mlh3", "proteins mlh1 and mlh3 are", "mlh1 and mlh3 are then", "and mlh3 are then recruited", "mlh3 are then recruited to", "are then recruited to the", "then recruited to the double", "recruited to the double holliday", "to the double holliday structure", "the double holliday structure and", "double holliday structure and an", "holliday structure and an unidentified", "structure and an unidentified resolvase", "an unidentified resolvase mus81?", "unidentified resolvase mus81? gen1?", "mus81? gen1? cleaves the", "gen1? cleaves the junctions", "cleaves the junctions to yield", "the junctions to yield a", "junctions to yield a crossover.", "to yield a crossover.
crossovers", "yield a crossover.
crossovers are", "a crossover.
crossovers are not", "crossover.
crossovers are not randomly", "
crossovers are not randomly distributed:", "are not randomly distributed: the", "not randomly distributed: the histone", "randomly distributed: the histone methyltransferase", "distributed: the histone methyltransferase prdm9", "the histone methyltransferase prdm9 recruits", "histone methyltransferase prdm9 recruits the", "methyltransferase prdm9 recruits the recombination", "prdm9 recruits the recombination machinery", "recruits the recombination machinery to", "the recombination machinery to genetically", "recombination machinery to genetically determined", "machinery to genetically determined hotspots", "to genetically determined hotspots in", "genetically determined hotspots in the", "determined hotspots in the genome", "hotspots in the genome and", "in the genome and each", "the genome and each incipient", "genome and each incipient crossover", "and each incipient crossover somehow", "each incipient crossover somehow inhibits", "incipient crossover somehow inhibits formation", "crossover somehow inhibits formation of", "somehow inhibits formation of crossovers", "inhibits formation of crossovers nearby", "of crossovers nearby a", "crossovers nearby a phenomenon", "nearby a phenomenon called", "a phenomenon called crossover interference.", "phenomenon called crossover interference. each", "called crossover interference. each chromosome", "crossover interference. each chromosome bivalent", "each chromosome bivalent including", "chromosome bivalent including the", "bivalent including the x", "including the x y body", "the x y body in", "x y body in males", "body in males has", "in males has at", "males has at least", "has at least one crossover", "at least one crossover and", "least one crossover and this", "one crossover and this is", "crossover and this is required", "and this is required for", "this is required for meiosis", "is required for meiosis to", "required for meiosis to proceed", "for meiosis to proceed correctly.

for", "meiosis to proceed correctly.

for review", "proceed correctly.

for review please", "correctly.

for review please refer", "review please refer to", "please refer to cohen et", "refer to cohen et al.", "to cohen et al. 2006", "et al. 2006 inagaki", "al. 2006 inagaki et", "2006 inagaki et al.", "et al. 2010 handel", "al. 2010 handel and", "2010 handel and schimenti", "handel and schimenti 2010.

the firrm:fignl1", "and schimenti 2010.

the firrm:fignl1 complex", "schimenti 2010.

the firrm:fignl1 complex has", "2010.

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figure", "ship.

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figure", "with ship.

figure reproduced", "ship.

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figure", "and with ship.

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copyright american society for", "american society for microbiology.", "society for microbiology. all", "for microbiology. all rights", "microbiology. all rights reserved.", "phosphorylation of shc at three", "of shc at three tyrosine", "shc at three tyrosine residues", "three tyrosine residues 239", "residues 239 240", "239 240 gotoh", "240 gotoh et al.", "et al. 1996 and", "al. 1996 and 317", "and 317 salcini et", "317 salcini et al.", "et al. 1994 involves", "al. 1994 involves unidentified", "1994 involves unidentified tyrosine", "involves unidentified tyrosine kinases presumed", "unidentified tyrosine kinases presumed to", "tyrosine kinases presumed to be", "kinases presumed to be part", "presumed to be part of", "to be part of the", "be part of the activated", "part of the activated receptor", "of the activated receptor complex.", "the activated receptor complex. these", "activated receptor complex. these phosphorylated", "receptor complex. these phosphorylated tyrosines", "complex. these phosphorylated tyrosines subsequently", "these phosphorylated tyrosines subsequently bind", "phosphorylated tyrosines subsequently bind sh2", "tyrosines subsequently bind sh2 signaling", "subsequently bind sh2 signaling proteins", "bind sh2 signaling proteins such", "sh2 signaling proteins such as", "signaling proteins such as grb2", "such as grb2 gab2", "as grb2 gab2 and", "grb2 gab2 and ship", "gab2 and ship that are", "and ship that are involved", "ship that are involved in", "that are involved in the", "are involved in the regulation", "involved in the regulation of", "in the regulation of different", "the regulation of different signaling", "regulation of different signaling pathways.", "of different signaling pathways. grb2", "different signaling pathways. grb2 can", "signaling pathways. grb2 can associate", "pathways. grb2 can associate with", "grb2 can associate with the", "can associate with the guanosine", "associate with the guanosine diphosphate", "with the guanosine diphosphate guanosine", "the guanosine diphosphate guanosine triphosphate", "guanosine diphosphate guanosine triphosphate exchange", "diphosphate guanosine triphosphate exchange factor", "guanosine triphosphate exchange factor sos1", "exchange factor sos1 leading", "factor sos1 leading to", "sos1 leading to ras", "leading to ras activation and", "to ras activation and regulation", "ras activation and regulation of", "activation and regulation of cell", "and regulation of cell proliferation.", "regulation of cell proliferation. downstream", "of cell proliferation. downstream signals", "cell proliferation. downstream signals are", "proliferation. downstream signals are mediated", "downstream signals are mediated via", "signals are mediated via the", "are mediated via the raf", "mediated via the raf mek", "via the raf mek erk", "the raf mek erk pathway.grb2", "raf mek erk pathway.grb2 can", "mek erk pathway.grb2 can also", "erk pathway.grb2 can also associate", "pathway.grb2 can also associate through", "can also associate through gab2", "also associate through gab2 with", "associate through gab2 with pi3k", "through gab2 with pi3k and", "gab2 with pi3k and with", "with pi3k and with ship.

figure", "pi3k and with ship.

figure reproduced", "and with ship.

figure reproduced from", "with ship.

figure reproduced from gu", "reproduced from gu h.", "from gu h. et", "gu h. et al.", "h. et al. 2000. mol.", "et al. 2000. mol. cell.", "al. 2000. mol. cell. biol.", "2000. mol. cell. biol. 20", "mol. cell. biol. 20 19", "cell. biol. 20 19 :7109", "biol. 20 19 :7109 7120
copyright", "20 19 :7109 7120
copyright american", "19 :7109 7120
copyright american society", ":7109 7120
copyright american society for", "7120
copyright american society for microbiology.", "american society for microbiology. all", "society for microbiology. all rights", "for microbiology. all rights reserved." ] }, { "record_id": "GLY_000594_1_676", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "912631", "r hsa", "hsa 912631", "r hsa 912631" ] }, { "record_id": "GLY_000594_1_676", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of signaling", "signaling by", "by cbl", "regulation of signaling", "of signaling by", "signaling by cbl", "regulation of signaling by", "of signaling by cbl", "regulation of signaling by cbl", "cbl is", "is an", "an e3", "e3 ubiquitin", "ubiquitin protein", "protein ligase", "ligase that", "that negatively", "negatively regulates", "regulates signaling", "signaling pathways", "pathways by", "by targeting", "targeting proteins", "proteins for", "for ubiquitination", "ubiquitination and", "and proteasomal", "proteasomal degradation", "rao et", "et al.", "al. 2002", "2002 .", ". cbl", "cbl negatively", "regulates pi3k", "pi3k via", "via this", "this mechanism", "dufour et", "al. 2008", "2008 .", ". the", "the binding", "binding of", "of cbl", "cbl to", "to the", "the p85", "p85 subunit", "subunit of", "of pi3k", "pi3k is", "is mediated", "mediated at", "at least", "least in", "in part", "part by", "by tyrosine", "tyrosine phosphorylation", "phosphorylation at", "at y731", ". fyn", "fyn and", "and the", "the related", "related kinases", "hck and", "and lyn", "lyn are", "are known", "known to", "to be", "be associated", "associated with", "with cbl", "anderson et", "al. 1997", "hunter et", "al. 1999", "1999 .", "fyn is", "is proven", "proven capable", "capable of", "cbl y731", "y731 phosphorylation", "1999 .the", ".the association", "association of", "of fyn", "and cbl", "cbl has", "has been", "been described", "described as", "as constitutive", "cbl further", "further associates", "associates with", "with the", "hartley et", "al. 1995", "this also", "also described", "constitutive and", "and mediated", "mediated by", "by the", "the sh3", "sh3 domain", "domain of", "of p85.", "p85. binding", "of the", "the sh2", "sh2 domain", "of p85", "p85 to", "to a", "a specific", "specific phosphorylation", "phosphorylation site", "site in", "in cbl", "is postulated", "postulated to", "to explain", "explain the", "the the", "the increase", "increase in", "in cbl/p85", "cbl/p85 association", "association seen", "seen in", "in activated", "activated cells", "panchamoorthy et", "et al", "al 1996", "which negatively", "pi3k activity", "fang et", "al. 2001", "2001 .", "the negative", "negative effect", "effect of", "of increased", "increased cbl", "cbl pi3k", "pi3k interaction", "interaction is", "by y731", "y731 of", "of cbl.", "cbl. cbl", "cbl binding", "binding increases", "increases pi3k", "pi3k ubiquitination", "and proteasome", "proteasome degradation", "2008 .


cbl", ".


cbl is", "is constitutively", "constitutively associated", "with grb", "grb in", "in resting", "resting hematopoietic", "hematopoietic cells", "odai et", "park et", "al. 1998", "al. 1996", "1996 .", ". both", "both the", "sh2 and", "and sh3", "sh3 domains", "domains of", "of grb2", "grb2 are", "are involved.", "involved. cbl", "has 2", "2 distinct", "distinct c", "c terminal", "terminal domains", "proximal and", "and distal.", "distal. the", "the proximal", "proximal domain", "domain binds", "binds grb2", "grb2 in", "resting and", "and stimulated", "stimulated cells", "and in", "in stimulated", "cells also", "also binds", "binds shc.", "shc. the", "the distal", "distal domain", "binds the", "the adaptor", "adaptor protein", "protein crkl.", "crkl. tyrosine", "phosphorylation of", "cbl in", "in response", "response to", "to il", "il 3", "3 releases", "releases the", "grb2 which", "which then", "then is", "is free", "free to", "to bind", "bind other", "other molecules", "1998 .", "is tyrosine", "tyrosine phosphorylated", "phosphorylated in", "to many", "many cytokines", "cytokines including", "including il", "il 2", "gesbert et", "and il", "il 4", "ueno et", "cbl is an", "is an e3", "an e3 ubiquitin", "e3 ubiquitin protein", "ubiquitin protein ligase", "protein ligase that", "ligase that negatively", "that negatively regulates", "negatively regulates signaling", "regulates signaling pathways", "signaling pathways by", "pathways by targeting", "by targeting proteins", "targeting proteins for", "proteins for ubiquitination", "for ubiquitination and", "ubiquitination and proteasomal", "and proteasomal degradation", "degradation rao", "rao et al.", "et al. 2002", "al. 2002 .", "2002 . cbl", ". cbl negatively", "cbl negatively regulates", "negatively regulates pi3k", "regulates pi3k via", "pi3k via this", "via this mechanism", "mechanism dufour", "dufour et al.", "et al. 2008", "al. 2008 .", "2008 . the", ". the binding", "the binding of", "binding of cbl", "of cbl to", "cbl to the", "to the p85", "the p85 subunit", "p85 subunit of", "subunit of pi3k", "of pi3k is", "pi3k is mediated", "is mediated at", "mediated at least", "at least in", "least in part", "in part by", "part by tyrosine", "by tyrosine phosphorylation", "tyrosine phosphorylation at", "phosphorylation at y731", "y731 dufour", "2008 . fyn", ". fyn and", "fyn and the", "and the related", "the related kinases", "kinases hck", "hck and lyn", "and lyn are", "lyn are known", "are known to", "known to be", "to be associated", "be associated with", "associated with cbl", "cbl anderson", "anderson et al.", "et al. 1997", "1997 hunter", "hunter et al.", "et al. 1999", "al. 1999 .", "1999 . fyn", ". fyn is", "fyn is proven", "is proven capable", "proven capable of", "capable of cbl", "of cbl y731", "cbl y731 phosphorylation", "phosphorylation hunter", "al. 1999 .the", "1999 .the association", ".the association of", "association of fyn", "of fyn and", "fyn and cbl", "and cbl has", "cbl has been", "has been described", "been described as", "described as constitutive", "constitutive hunter", "1999 . cbl", ". cbl further", "cbl further associates", "further associates with", "associates with the", "with the p85", "pi3k hartley", "hartley et al.", "et al. 1995", "1995 anderson", "this also described", "also described as", "as constitutive and", "constitutive and mediated", "and mediated by", "mediated by the", "by the sh3", "the sh3 domain", "sh3 domain of", "domain of p85.", "of p85. binding", "p85. binding of", "binding of the", "of the sh2", "the sh2 domain", "sh2 domain of", "domain of p85", "of p85 to", "p85 to a", "to a specific", "a specific phosphorylation", "specific phosphorylation site", "phosphorylation site in", "site in cbl", "in cbl is", "cbl is postulated", "is postulated to", "postulated to explain", "to explain the", "explain the the", "the the increase", "the increase in", "increase in cbl/p85", "in cbl/p85 association", "cbl/p85 association seen", "association seen in", "seen in activated", "in activated cells", "cells panchamoorthy", "panchamoorthy et al", "et al 1996", "1996 which", "which negatively regulates", "regulates pi3k activity", "activity fang", "fang et al.", "et al. 2001", "al. 2001 .", "2001 . the", ". the negative", "the negative effect", "negative effect of", "effect of increased", "of increased cbl", "increased cbl pi3k", "cbl pi3k interaction", "pi3k interaction is", "interaction is mediated", "is mediated by", "mediated by y731", "by y731 of", "y731 of cbl.", "of cbl. cbl", "cbl. cbl binding", "cbl binding increases", "binding increases pi3k", "increases pi3k ubiquitination", "pi3k ubiquitination and", "ubiquitination and proteasome", "and proteasome degradation", "degradation dufour", "al. 2008 .


cbl", "2008 .


cbl is", ".


cbl is constitutively", "is constitutively associated", "constitutively associated with", "associated with grb", "with grb in", "grb in resting", "in resting hematopoietic", "resting hematopoietic cells", "cells anderson", "1997 odai", "odai et al.", "1995 park", "park et al.", "et al. 1998", "1998 panchamoorthy", "panchamoorthy et al.", "et al. 1996", "al. 1996 .", "1996 . both", ". both the", "both the sh2", "the sh2 and", "sh2 and sh3", "and sh3 domains", "sh3 domains of", "domains of grb2", "of grb2 are", "grb2 are involved.", "are involved. cbl", "involved. cbl has", "cbl has 2", "has 2 distinct", "2 distinct c", "distinct c terminal", "c terminal domains", "domains proximal", "proximal and distal.", "and distal. the", "distal. the proximal", "the proximal domain", "proximal domain binds", "domain binds grb2", "binds grb2 in", "grb2 in resting", "in resting and", "resting and stimulated", "and stimulated cells", "cells and", "and in stimulated", "in stimulated cells", "stimulated cells also", "cells also binds", "also binds shc.", "binds shc. the", "shc. the distal", "the distal domain", "distal domain binds", "domain binds the", "binds the adaptor", "the adaptor protein", "adaptor protein crkl.", "protein crkl. tyrosine", "crkl. tyrosine phosphorylation", "tyrosine phosphorylation of", "phosphorylation of cbl", "of cbl in", "cbl in response", "in response to", "response to il", "to il 3", "il 3 releases", "3 releases the", "releases the sh3", "domain of grb2", "of grb2 which", "grb2 which then", "which then is", "then is free", "is free to", "free to bind", "to bind other", "bind other molecules", "molecules park", "al. 1998 .", "1998 . cbl", ". cbl is", "cbl is tyrosine", "is tyrosine phosphorylated", "tyrosine phosphorylated in", "phosphorylated in response", "response to many", "to many cytokines", "many cytokines including", "cytokines including il", "including il 3", "3 il", "2 gesbert", "gesbert et al.", "1998 and", "and il 4", "4 ueno", "ueno et al.", "cbl is an e3", "is an e3 ubiquitin", "an e3 ubiquitin protein", "e3 ubiquitin protein ligase", "ubiquitin protein ligase that", "protein ligase that negatively", "ligase that negatively regulates", "that negatively regulates signaling", "negatively regulates signaling pathways", "regulates signaling pathways by", "signaling pathways by targeting", "pathways by targeting proteins", "by targeting proteins for", "targeting proteins for ubiquitination", "proteins for ubiquitination and", "for ubiquitination and proteasomal", "ubiquitination and proteasomal degradation", "proteasomal degradation rao", "degradation rao et", "rao et al. 2002", "et al. 2002 .", "al. 2002 . cbl", "2002 . cbl negatively", ". cbl negatively regulates", "cbl negatively regulates pi3k", "negatively regulates pi3k via", "regulates pi3k via this", "pi3k via this mechanism", "this mechanism dufour", "mechanism dufour et", "dufour et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the binding", ". the binding of", "the binding of cbl", "binding of cbl to", "of cbl to the", "cbl to the p85", "to the p85 subunit", "the p85 subunit of", "p85 subunit of pi3k", "subunit of pi3k is", "of pi3k is mediated", "pi3k is mediated at", "is mediated at least", "mediated at least in", "at least in part", "least in part by", "in part by tyrosine", "part by tyrosine phosphorylation", "by tyrosine phosphorylation at", "tyrosine phosphorylation at y731", "at y731 dufour", "y731 dufour et", "al. 2008 . fyn", "2008 . fyn and", ". fyn and the", "fyn and the related", "and the related kinases", "related kinases hck", "kinases hck and", "hck and lyn are", "and lyn are known", "lyn are known to", "are known to be", "known to be associated", "to be associated with", "be associated with cbl", "with cbl anderson", "cbl anderson et", "anderson et al. 1997", "al. 1997 hunter", "1997 hunter et", "hunter et al. 1999", "et al. 1999 .", "al. 1999 . fyn", "1999 . fyn is", ". fyn is proven", "fyn is proven capable", "is proven capable of", "proven capable of cbl", "capable of cbl y731", "of cbl y731 phosphorylation", "y731 phosphorylation hunter", "phosphorylation hunter et", "et al. 1999 .the", "al. 1999 .the association", "1999 .the association of", ".the association of fyn", "association of fyn and", "of fyn and cbl", "fyn and cbl has", "and cbl has been", "cbl has been described", "has been described as", "been described as constitutive", "as constitutive hunter", "constitutive hunter et", "al. 1999 . cbl", "1999 . cbl further", ". cbl further associates", "cbl further associates with", "further associates with the", "associates with the p85", "with the p85 subunit", "of pi3k hartley", "pi3k hartley et", "hartley et al. 1995", "al. 1995 anderson", "1995 anderson et", "hunter et al. 1997", "1997 this", "this also described as", "also described as constitutive", "described as constitutive and", "as constitutive and mediated", "constitutive and mediated by", "and mediated by the", "mediated by the sh3", "by the sh3 domain", "the sh3 domain of", "sh3 domain of p85.", "domain of p85. binding", "of p85. binding of", "p85. binding of the", "binding of the sh2", "of the sh2 domain", "the sh2 domain of", "sh2 domain of p85", "domain of p85 to", "of p85 to a", "p85 to a specific", "to a specific phosphorylation", "a specific phosphorylation site", "specific phosphorylation site in", "phosphorylation site in cbl", "site in cbl is", "in cbl is postulated", "cbl is postulated to", "is postulated to explain", "postulated to explain the", "to explain the the", "explain the the increase", "the the increase in", "the increase in cbl/p85", "increase in cbl/p85 association", "in cbl/p85 association seen", "cbl/p85 association seen in", "association seen in activated", "seen in activated cells", "activated cells panchamoorthy", "cells panchamoorthy et", "panchamoorthy et al 1996", "al 1996 which", "1996 which negatively", "which negatively regulates pi3k", "negatively regulates pi3k activity", "pi3k activity fang", "activity fang et", "fang et al. 2001", "et al. 2001 .", "al. 2001 . the", "2001 . the negative", ". the negative effect", "the negative effect of", "negative effect of increased", "effect of increased cbl", "of increased cbl pi3k", "increased cbl pi3k interaction", "cbl pi3k interaction is", "pi3k interaction is mediated", "interaction is mediated by", "is mediated by y731", "mediated by y731 of", "by y731 of cbl.", "y731 of cbl. cbl", "of cbl. cbl binding", "cbl. cbl binding increases", "cbl binding increases pi3k", "binding increases pi3k ubiquitination", "increases pi3k ubiquitination and", "pi3k ubiquitination and proteasome", "ubiquitination and proteasome degradation", "proteasome degradation dufour", "degradation dufour et", "et al. 2008 .


cbl", "al. 2008 .


cbl is", "2008 .


cbl is constitutively", ".


cbl is constitutively associated", "is constitutively associated with", "constitutively associated with grb", "associated with grb in", "with grb in resting", "grb in resting hematopoietic", "in resting hematopoietic cells", "hematopoietic cells anderson", "cells anderson et", "al. 1997 odai", "1997 odai et", "odai et al. 1995", "al. 1995 park", "1995 park et", "park et al. 1998", "al. 1998 panchamoorthy", "1998 panchamoorthy et", "panchamoorthy et al. 1996", "et al. 1996 .", "al. 1996 . both", "1996 . both the", ". both the sh2", "both the sh2 and", "the sh2 and sh3", "sh2 and sh3 domains", "and sh3 domains of", "sh3 domains of grb2", "domains of grb2 are", "of grb2 are involved.", "grb2 are involved. cbl", "are involved. cbl has", "involved. cbl has 2", "cbl has 2 distinct", "has 2 distinct c", "2 distinct c terminal", "distinct c terminal domains", "terminal domains proximal", "domains proximal and", "proximal and distal. the", "and distal. the proximal", "distal. the proximal domain", "the proximal domain binds", "proximal domain binds grb2", "domain binds grb2 in", "binds grb2 in resting", "grb2 in resting and", "in resting and stimulated", "resting and stimulated cells", "stimulated cells and", "cells and in", "and in stimulated cells", "in stimulated cells also", "stimulated cells also binds", "cells also binds shc.", "also binds shc. the", "binds shc. the distal", "shc. the distal domain", "the distal domain binds", "distal domain binds the", "domain binds the adaptor", "binds the adaptor protein", "the adaptor protein crkl.", "adaptor protein crkl. tyrosine", "protein crkl. tyrosine phosphorylation", "crkl. tyrosine phosphorylation of", "tyrosine phosphorylation of cbl", "phosphorylation of cbl in", "of cbl in response", "cbl in response to", "in response to il", "response to il 3", "to il 3 releases", "il 3 releases the", "3 releases the sh3", "releases the sh3 domain", "sh3 domain of grb2", "domain of grb2 which", "of grb2 which then", "grb2 which then is", "which then is free", "then is free to", "is free to bind", "free to bind other", "to bind other molecules", "other molecules park", "molecules park et", "et al. 1998 .", "al. 1998 . cbl", "1998 . cbl is", ". cbl is tyrosine", "cbl is tyrosine phosphorylated", "is tyrosine phosphorylated in", "tyrosine phosphorylated in response", "phosphorylated in response to", "in response to many", "response to many cytokines", "to many cytokines including", "many cytokines including il", "cytokines including il 3", "il 3 il", "3 il 2", "il 2 gesbert", "2 gesbert et", "gesbert et al. 1998", "al. 1998 and", "1998 and il", "il 4 ueno", "4 ueno et", "ueno et al. 1998", "cbl is an e3 ubiquitin", "is an e3 ubiquitin protein", "an e3 ubiquitin protein ligase", "e3 ubiquitin protein ligase that", "ubiquitin protein ligase that negatively", "protein ligase that negatively regulates", "ligase that negatively regulates signaling", "that negatively regulates signaling pathways", "negatively regulates signaling pathways by", "regulates signaling pathways by targeting", "signaling pathways by targeting proteins", "pathways by targeting proteins for", "by targeting proteins for ubiquitination", "targeting proteins for ubiquitination and", "proteins for ubiquitination and proteasomal", "for ubiquitination and proteasomal degradation", "and proteasomal degradation rao", "proteasomal degradation rao et", "degradation rao et al.", "rao et al. 2002 .", "et al. 2002 . cbl", "al. 2002 . cbl negatively", "2002 . cbl negatively regulates", ". cbl negatively regulates pi3k", "cbl negatively regulates pi3k via", "negatively regulates pi3k via this", "regulates pi3k via this mechanism", "via this mechanism dufour", "this mechanism dufour et", "mechanism dufour et al.", "dufour et al. 2008 .", "et al. 2008 . the", "al. 2008 . the binding", "2008 . the binding of", ". the binding of cbl", "the binding of cbl to", "binding of cbl to the", "of cbl to the p85", "cbl to the p85 subunit", "to the p85 subunit of", "the p85 subunit of pi3k", "p85 subunit of pi3k is", "subunit of pi3k is mediated", "of pi3k is mediated at", "pi3k is mediated at least", "is mediated at least in", "mediated at least in part", "at least in part by", "least in part by tyrosine", "in part by tyrosine phosphorylation", "part by tyrosine phosphorylation at", "by tyrosine phosphorylation at y731", "phosphorylation at y731 dufour", "at y731 dufour et", "y731 dufour et al.", "et al. 2008 . fyn", "al. 2008 . fyn and", "2008 . fyn and the", ". fyn and the related", "fyn and the related kinases", "the related kinases hck", "related kinases hck and", "kinases hck and lyn", "hck and lyn are known", "and lyn are known to", "lyn are known to be", "are known to be associated", "known to be associated with", "to be associated with cbl", "associated with cbl anderson", "with cbl anderson et", "cbl anderson et al.", "et al. 1997 hunter", "al. 1997 hunter et", "1997 hunter et al.", "hunter et al. 1999 .", "et al. 1999 . fyn", "al. 1999 . fyn is", "1999 . fyn is proven", ". fyn is proven capable", "fyn is proven capable of", "is proven capable of cbl", "proven capable of cbl y731", "capable of cbl y731 phosphorylation", "cbl y731 phosphorylation hunter", "y731 phosphorylation hunter et", "phosphorylation hunter et al.", "hunter et al. 1999 .the", "et al. 1999 .the association", "al. 1999 .the association of", "1999 .the association of fyn", ".the association of fyn and", "association of fyn and cbl", "of fyn and cbl has", "fyn and cbl has been", "and cbl has been described", "cbl has been described as", "has been described as constitutive", "described as constitutive hunter", "as constitutive hunter et", "constitutive hunter et al.", "et al. 1999 . cbl", "al. 1999 . cbl further", "1999 . cbl further associates", ". cbl further associates with", "cbl further associates with the", "further associates with the p85", "associates with the p85 subunit", "with the p85 subunit of", "subunit of pi3k hartley", "of pi3k hartley et", "pi3k hartley et al.", "et al. 1995 anderson", "al. 1995 anderson et", "1995 anderson et al.", "al. 1997 this", "1997 this also", "this also described as constitutive", "also described as constitutive and", "described as constitutive and mediated", "as constitutive and mediated by", "constitutive and mediated by the", "and mediated by the sh3", "mediated by the sh3 domain", "by the sh3 domain of", "the sh3 domain of p85.", "sh3 domain of p85. binding", "domain of p85. binding of", "of p85. binding of the", "p85. binding of the sh2", "binding of the sh2 domain", "of the sh2 domain of", "the sh2 domain of p85", "sh2 domain of p85 to", "domain of p85 to a", "of p85 to a specific", "p85 to a specific phosphorylation", "to a specific phosphorylation site", "a specific phosphorylation site in", "specific phosphorylation site in cbl", "phosphorylation site in cbl is", "site in cbl is postulated", "in cbl is postulated to", "cbl is postulated to explain", "is postulated to explain the", "postulated to explain the the", "to explain the the increase", "explain the the increase in", "the the increase in cbl/p85", "the increase in cbl/p85 association", "increase in cbl/p85 association seen", "in cbl/p85 association seen in", "cbl/p85 association seen in activated", "association seen in activated cells", "in activated cells panchamoorthy", "activated cells panchamoorthy et", "cells panchamoorthy et al", "et al 1996 which", "al 1996 which negatively", "1996 which negatively regulates", "which negatively regulates pi3k activity", "regulates pi3k activity fang", "pi3k activity fang et", "activity fang et al.", "fang et al. 2001 .", "et al. 2001 . the", "al. 2001 . the negative", "2001 . the negative effect", ". the negative effect of", "the negative effect of increased", "negative effect of increased cbl", "effect of increased cbl pi3k", "of increased cbl pi3k interaction", "increased cbl pi3k interaction is", "cbl pi3k interaction is mediated", "pi3k interaction is mediated by", "interaction is mediated by y731", "is mediated by y731 of", "mediated by y731 of cbl.", "by y731 of cbl. cbl", "y731 of cbl. cbl binding", "of cbl. cbl binding increases", "cbl. cbl binding increases pi3k", "cbl binding increases pi3k ubiquitination", "binding increases pi3k ubiquitination and", "increases pi3k ubiquitination and proteasome", "pi3k ubiquitination and proteasome degradation", "and proteasome degradation dufour", "proteasome degradation dufour et", "degradation dufour et al.", "dufour et al. 2008 .


cbl", "et al. 2008 .


cbl is", "al. 2008 .


cbl is constitutively", "2008 .


cbl is constitutively associated", ".


cbl is constitutively associated with", "is constitutively associated with grb", "constitutively associated with grb in", "associated with grb in resting", "with grb in resting hematopoietic", "grb in resting hematopoietic cells", "resting hematopoietic cells anderson", "hematopoietic cells anderson et", "cells anderson et al.", "et al. 1997 odai", "al. 1997 odai et", "1997 odai et al.", "et al. 1995 park", "al. 1995 park et", "1995 park et al.", "et al. 1998 panchamoorthy", "al. 1998 panchamoorthy et", "1998 panchamoorthy et al.", "panchamoorthy et al. 1996 .", "et al. 1996 . both", "al. 1996 . both the", "1996 . both the sh2", ". both the sh2 and", "both the sh2 and sh3", "the sh2 and sh3 domains", "sh2 and sh3 domains of", "and sh3 domains of grb2", "sh3 domains of grb2 are", "domains of grb2 are involved.", "of grb2 are involved. cbl", "grb2 are involved. cbl has", "are involved. cbl has 2", "involved. cbl has 2 distinct", "cbl has 2 distinct c", "has 2 distinct c terminal", "2 distinct c terminal domains", "c terminal domains proximal", "terminal domains proximal and", "domains proximal and distal.", "proximal and distal. the proximal", "and distal. the proximal domain", "distal. the proximal domain binds", "the proximal domain binds grb2", "proximal domain binds grb2 in", "domain binds grb2 in resting", "binds grb2 in resting and", "grb2 in resting and stimulated", "in resting and stimulated cells", "and stimulated cells and", "stimulated cells and in", "cells and in stimulated", "and in stimulated cells also", "in stimulated cells also binds", "stimulated cells also binds shc.", "cells also binds shc. the", "also binds shc. the distal", "binds shc. the distal domain", "shc. the distal domain binds", "the distal domain binds the", "distal domain binds the adaptor", "domain binds the adaptor protein", "binds the adaptor protein crkl.", "the adaptor protein crkl. tyrosine", "adaptor protein crkl. tyrosine phosphorylation", "protein crkl. tyrosine phosphorylation of", "crkl. tyrosine phosphorylation of cbl", "tyrosine phosphorylation of cbl in", "phosphorylation of cbl in response", "of cbl in response to", "cbl in response to il", "in response to il 3", "response to il 3 releases", "to il 3 releases the", "il 3 releases the sh3", "3 releases the sh3 domain", "releases the sh3 domain of", "the sh3 domain of grb2", "sh3 domain of grb2 which", "domain of grb2 which then", "of grb2 which then is", "grb2 which then is free", "which then is free to", "then is free to bind", "is free to bind other", "free to bind other molecules", "bind other molecules park", "other molecules park et", "molecules park et al.", "park et al. 1998 .", "et al. 1998 . cbl", "al. 1998 . cbl is", "1998 . cbl is tyrosine", ". cbl is tyrosine phosphorylated", "cbl is tyrosine phosphorylated in", "is tyrosine phosphorylated in response", "tyrosine phosphorylated in response to", "phosphorylated in response to many", "in response to many cytokines", "response to many cytokines including", "to many cytokines including il", "many cytokines including il 3", "including il 3 il", "il 3 il 2", "il 2 gesbert et", "2 gesbert et al.", "et al. 1998 and", "al. 1998 and il", "1998 and il 4", "and il 4 ueno", "il 4 ueno et", "4 ueno et al.", "ueno et al. 1998 ." ] }, { "record_id": "GLY_000594_1_677", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "912694", "r hsa", "hsa 912694", "r hsa 912694" ] }, { "record_id": "GLY_000594_1_677", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of ifna/ifnb", "ifna/ifnb signaling", "regulation of ifna/ifnb", "of ifna/ifnb signaling", "regulation of ifna/ifnb signaling", "there are", "are several", "several proteins", "proteins and", "and mechanisms", "mechanisms involved", "involved in", "in controlling", "controlling the", "the extent", "extent of", "of ligand", "ligand stimulation", "stimulation of", "of 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"mediated production of", "production of ifn", "of ifn can", "can in", "turn increase", "increase the transcription", "the transcription of", "transcription of rig", "of rig i", "rig i itself", "itself thus", "thus setting into", "setting into motion", "into motion an", "motion an ifn", "an ifn amplification", "ifn amplification loop", "loop which", "which if left", "if left unchecked", "unchecked could", "could become deleterious", "become deleterious to", "deleterious to the", "to the host.", "the host. this", "host. this module", "this module mainly", "module mainly focuses", "mainly focuses on", "focuses on the", "on the endogenous", "the endogenous negative", "endogenous negative regulation", "negative regulation of", "regulation of the", "of the rig", "the rig i", "rig i like", "i like receptor", "receptor rlr", "rlr family", "family proteins rig", "proteins rig i", "i ddx58", "ddx58 and", "mda5 ifih1", "as with other cytokine", "with other cytokine systems", "cytokine systems production", "systems production of", "production of type i", "of type i ifn", "type i ifn is", "i ifn is a", "ifn is a transient", "is a transient process", "transient process and", "process and can", "and can be hazardous", "can be hazardous to", "be hazardous to the", "hazardous to the host", "to the host if", "the host if unregulated", "if unregulated resulting", "unregulated resulting in", "resulting in chronic cellular", "in chronic cellular toxicity", "chronic cellular toxicity or", "cellular toxicity or inflammatory", "toxicity or inflammatory and", "or inflammatory and autoimmune", "inflammatory and autoimmune diseases.", "and autoimmune diseases. rig", "autoimmune diseases. rig i", "diseases. rig i mediated", "rig i mediated production", "i mediated production of", "mediated production of ifn", "production of ifn can", "ifn can in", "can in turn", "in turn increase", "turn increase the", "increase the transcription of", "the transcription of rig", "transcription of rig i", "of rig i itself", "i itself thus", "itself thus setting", "thus setting into motion", "setting into motion an", "into motion an ifn", "motion an ifn amplification", "an ifn amplification loop", "amplification loop which", "loop which if", "which if left unchecked", "left unchecked could", "unchecked could become", "could become deleterious to", "become deleterious to the", "deleterious to the host.", "to the host. this", "the host. this module", "host. this module mainly", "this module mainly focuses", "module mainly focuses on", "mainly focuses on the", "focuses on the endogenous", "on the endogenous negative", "the endogenous negative regulation", "endogenous negative regulation of", "negative regulation of the", "regulation of the rig", "of the rig i", "the rig i like", "rig i like receptor", "like receptor rlr", "rlr family proteins", "family proteins rig i", "rig i ddx58", "ddx58 and mda5", "and mda5 ifih1", "mda5 ifih1 .", "as with other cytokine systems", "other cytokine systems production", "cytokine systems production of", "systems production of type", "production of type i ifn", "of type i ifn is", "type i ifn is a", "i ifn is a transient", "ifn is a transient process", "a transient process and", "transient process and can", "process and can be", "and can be hazardous to", "can be hazardous to the", "be hazardous to the host", "hazardous to the host if", "to the host if unregulated", "host if unregulated resulting", "if unregulated resulting in", "unregulated resulting in chronic", "resulting in chronic cellular toxicity", "in chronic cellular toxicity or", "chronic cellular toxicity or inflammatory", "cellular toxicity or inflammatory and", "toxicity or inflammatory and autoimmune", "or inflammatory and autoimmune diseases.", "inflammatory and autoimmune diseases. rig", "and autoimmune diseases. rig i", "autoimmune diseases. rig i mediated", "diseases. rig i mediated production", "rig i mediated production of", "i mediated production of ifn", "mediated production of ifn can", "of ifn can in", "ifn can in turn", "in turn increase the", "turn increase the transcription", "increase the transcription of rig", "the transcription of rig i", "transcription of rig i itself", "rig i itself thus", "i itself thus setting", "itself thus setting into", "thus setting into motion an", "setting into motion an ifn", "into motion an ifn amplification", "motion an ifn amplification loop", "ifn amplification loop which", "amplification loop which if", "loop which if left", "if left unchecked could", "left unchecked could become", "unchecked could become deleterious", "could become deleterious to the", "become deleterious to the host.", "deleterious to the host. this", "to the host. this module", "the host. this module mainly", "host. this module mainly focuses", "this module mainly focuses on", "module mainly focuses on the", "mainly focuses on the endogenous", "focuses on the endogenous negative", "on the endogenous negative regulation", "the endogenous negative regulation of", "endogenous negative regulation of the", "negative regulation of the rig", "regulation of the rig i", "of the rig i like", "the rig i like receptor", "i like receptor rlr", "receptor rlr family", "rlr family proteins rig", "proteins rig i ddx58", "i ddx58 and", "and mda5 ifih1 ." ] }, { "record_id": "GLY_000594_1_683", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "936837", "r hsa", "hsa 936837", "r hsa 936837" ] }, { "record_id": "GLY_000594_1_683", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ion transport", "transport by", "by p", "p type", "type atpases", "ion transport by", "transport by p", "by p type", "p type atpases", "ion transport by p", "transport by p type", "by p type atpases", "ion transport by p type", "transport by p type atpases", "the p", "e1 e2", "e2 atpases", "are a", "a large", "large group", "group of", "of evolutionarily", "evolutionarily related", "related ion", "ion pumps", "pumps that", "that are", "are found", "found in", "in bacteria", "and eukaryotes.", "eukaryotes. they", "they are", "are referred", "referred to", "to as", "as p", "atpases because", "because they", "they catalyze", "catalyze auto", "auto phosphorylation", "phosphorylation of", "of a", "a key", "key conserved", "conserved aspartate", "aspartate residue", "residue within", "within the", "the pump.", "pump. they", "they all", "all appear", "appear to", "to interconvert", "interconvert between", "between at", "at least", "least two", "two different", "different conformations", "e1 and", "and e2.", "e2. most", "most members", "members of", "of this", "this transporter", "transporter family", "family pump", "pump a", "large variety", "variety of", "of cations", "kuhlbrandt w", "2004 .", "the p type", "atpases e1", "e1 e2 atpases", "atpases are", "are a large", "a large group", "large group of", "group of evolutionarily", "of evolutionarily related", "evolutionarily related ion", "related ion pumps", "ion pumps that", "pumps that are", "that are found", "are found in", "found in bacteria", "bacteria archaea", "archaea and", "and eukaryotes. they", "eukaryotes. they are", "they are referred", "are referred to", "referred to as", "to as p", "as p type", "type atpases because", "atpases because they", "because they catalyze", "they catalyze auto", "catalyze auto phosphorylation", "auto phosphorylation of", "phosphorylation of a", "of a key", "a key conserved", "key conserved aspartate", "conserved aspartate residue", "aspartate residue within", "residue within the", "within the pump.", "the pump. they", "pump. they all", "they all appear", "all appear to", "appear to interconvert", "to interconvert between", "interconvert between at", "between at least", "at least two", "least two different", "two different conformations", "conformations e1", "e1 and e2.", "and e2. most", "e2. most members", "most members of", "members of this", "of this transporter", "this transporter family", "transporter family pump", "family pump a", "pump a large", "a large variety", "large variety of", "variety of cations", "cations kuhlbrandt", "w 2004", "the p type atpases", "type atpases e1", "atpases e1 e2", "e2 atpases are", "atpases are a", "are a large group", "a large group of", "large group of evolutionarily", "group of evolutionarily related", "of evolutionarily related ion", "evolutionarily related ion pumps", "related ion pumps that", "ion pumps that are", "pumps that are found", "that are found in", "are found in bacteria", "in bacteria archaea", "archaea and eukaryotes.", "and eukaryotes. they are", "eukaryotes. they are referred", "they are referred to", "are referred to as", "referred to as p", "to as p type", "as p type atpases", "p type atpases because", "type atpases because they", "atpases because they catalyze", "because they catalyze auto", "they catalyze auto phosphorylation", "catalyze auto phosphorylation of", "auto phosphorylation of a", "phosphorylation of a key", "of a key conserved", "a key conserved aspartate", "key conserved aspartate residue", "conserved aspartate residue within", "aspartate residue within the", "residue within the pump.", "within the pump. they", "the pump. they all", "pump. they all appear", "they all appear to", "all appear to interconvert", "appear to interconvert between", "to interconvert between at", "interconvert between at least", "between at least two", "at least two different", "least two different conformations", "different conformations e1", "conformations e1 and", "e1 and e2. most", "and e2. most members", "e2. most members of", "most members of this", "members of this transporter", "of this transporter family", "this transporter family pump", "transporter family pump a", "family pump a large", "pump a large variety", "a large variety of", "large variety of cations", "of cations kuhlbrandt", "cations kuhlbrandt w", "kuhlbrandt w 2004", "w 2004 .", "p type atpases e1", "type atpases e1 e2", "atpases e1 e2 atpases", "e1 e2 atpases are", "e2 atpases are a", "atpases are a large", "are a large group of", "a large group of evolutionarily", "large group of evolutionarily related", "group of evolutionarily related ion", "of evolutionarily related ion pumps", "evolutionarily related ion pumps that", "related ion pumps that are", "ion pumps that are found", "pumps that are found in", "that are found in bacteria", "found in bacteria archaea", "bacteria archaea and", "archaea and eukaryotes. they", "and eukaryotes. they are referred", "eukaryotes. they are referred to", "they are referred to as", "are referred to as p", "referred to as p type", "to as p type atpases", "as p type atpases because", "p type atpases because they", "type atpases because they catalyze", "atpases because they catalyze auto", "because they catalyze auto phosphorylation", "they catalyze auto phosphorylation of", "catalyze auto phosphorylation of a", "auto phosphorylation of a key", "phosphorylation of a key conserved", "of a key conserved aspartate", "a key conserved aspartate residue", "key conserved aspartate residue within", "conserved aspartate residue within the", "aspartate residue within the pump.", "residue within the pump. they", "within the pump. they all", "the pump. they all appear", "pump. they all appear to", "they all appear to interconvert", "all appear to interconvert between", "appear to interconvert between at", "to interconvert between at least", "interconvert between at least two", "between at least two different", "at least two different conformations", "two different conformations e1", "different conformations e1 and", "conformations e1 and e2.", "e1 and e2. most members", "and e2. most members of", "e2. most members of this", "most members of this transporter", "members of this transporter family", "of this transporter family pump", "this transporter family pump a", "transporter family pump a large", "family pump a large variety", "pump a large variety of", "a large variety of cations", "variety of cations kuhlbrandt", "of cations kuhlbrandt w", "kuhlbrandt w 2004 ." ] }, { "record_id": "GLY_000594_1_684", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "936964", "r hsa", "hsa 936964", "r hsa 936964" ] }, { "record_id": "GLY_000594_1_684", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of irf3", "irf7 mediated", "mediated by", "by tbk1", "activation of irf3", "irf3 irf7", "irf7 mediated by", "mediated by tbk1", "tbk1 ikk\u03b5", "ikk\u03b5 ikbke", "of irf3 irf7", "irf3 irf7 mediated", "irf7 mediated by tbk1", "by tbk1 ikk\u03b5", "activation of irf3 irf7", "of irf3 irf7 mediated", "irf3 irf7 mediated by", "mediated by tbk1 ikk\u03b5", "tbk1 ikk\u03b5 ikbke", "cell stimulation", "stimulation with", "with viral", "viral double", "double stranded", "rna and", "and bacterial", "bacterial lipopolysaccharide", "activate toll", "toll like", "like receptors", "receptors 3", "and tlr4", "triggering the", "the activation", "activation the", "of two", "two ikk", "ikk related", "related serine/threonine", "serine/threonine kinases", "tank binding", "binding kinase", "kinase 1", "and i\u03bab", "i\u03bab kinase", "kinase \u03b5", "which directly", "directly phosphorylate", "phosphorylate interferon", "interferon regulatory", "regulatory factor", "factor 3", "and irf7", "irf7 promoting", "promoting their", "their dimerization", "dimerization and", "and translocation", "translocation into", "into the", "the nucleus.", "nucleus. although", "although both", "both kinases", "kinases show", "show structural", "structural and", "and functional", "functional similarities", "it seems", "seems that", "that tbk1", "tbk1 and", "and ikbke", "ikbke differ", "differ in", "in their", "their regulation", "regulation of", "of downstream", "downstream signaling", "signaling events", "events of", "of tlr3/tlr4.", "tlr3/tlr4.

irf3", "

irf3 activation", "activation and", "and interferon", "interferon \u03b2", "production by", "by poly", "poly i:c", "a synthetic", "synthetic analog", "analog of", "of dsrna", "are decreased", "decreased in", "in tbk1", "tbk1 deficient", "deficient mouse", "mouse fibroblasts", "whereas normal", "normal activation", "activation was", "was observed", "observed in", "in the", "the ikbke", "ikbke deficient", "deficient fibroblasts.", "fibroblasts. however", "in double", "double deficient", "irf3 is", "is completely", "completely abolished", "suggesting a", "a partially", "partially redundant", "redundant functions", "functions of", "of tbk1", "and ikk\u03b5", "hemmi h", "h et", "et al.", "2004 .", ".

the", "

the poly", "induced phosphorylation", "phosphorylation of", "and irf3", "irf3 was", "was abolished", "abolished in", "in trif", "knockout human", "human keratinocyte", "keratinocyte hacat", "hacat cells", "bakshi s", "s et", "2017 .", ". ticam1", "ticam1 is", "is utilized", "utilized as", "as an", "an adaptor", "adaptor protein", "protein by", "by tlr3", "tlr3 and", "yamamoto m", "m et", "2003 .", ".

tlr3", "

tlr3 recruits", "recruits and", "and activates", "activates pi3", "pi3 kinase", "which activates", "activates the", "the downstream", "downstream kinase", "leading to", "to full", "full phosphorylation", "phosphorylation and", "and activation", "sarkar sn", "sn et", ". when", "when pi3k", "pi3k is", "is not", "not recruited", "recruited to", "to tlr3", "tlr3 or", "or its", "its activity", "activity is", "is blocked", "is only", "only partially", "partially phosphorylated", "phosphorylated and", "and fails", "fails to", "to bind", "bind the", "the promoter", "promoter of", "of the", "the target", "target gene", "cell stimulation with", "stimulation with viral", "with viral double", "viral double stranded", "stranded ds", "ds rna", "rna and bacterial", "and bacterial lipopolysaccharide", "lipopolysaccharide lps", "lps activate", "activate toll like", "toll like receptors", "like receptors 3", "3 tlr3", "tlr4 respectively", "respectively triggering", "triggering the activation", "the activation the", "activation the activation", "the activation of", "activation of two", "of two ikk", "two ikk related", "ikk related serine/threonine", "related serine/threonine kinases", "kinases tank", "tank binding kinase", "binding kinase 1", "1 tbk1", "and i\u03bab kinase", "i\u03bab kinase \u03b5", "\u03b5 ikk\u03b5", "ikbke which", "which directly phosphorylate", "directly phosphorylate interferon", "phosphorylate interferon regulatory", "interferon regulatory factor", "regulatory factor 3", "3 irf3", "irf3 and", "and irf7 promoting", "irf7 promoting their", "promoting their dimerization", "their dimerization and", "dimerization and translocation", "and translocation into", "translocation into the", "into the nucleus.", "the nucleus. although", "nucleus. although both", "although both kinases", "both kinases show", "kinases show structural", "show structural and", "structural and functional", "and functional similarities", "similarities it", "it seems that", "seems that tbk1", "that tbk1 and", "tbk1 and ikbke", "and ikbke differ", "ikbke differ in", "differ in their", "in their regulation", "their regulation of", "regulation of downstream", "of downstream signaling", "downstream signaling events", "signaling events of", "events of tlr3/tlr4.", "of tlr3/tlr4.

irf3", "tlr3/tlr4.

irf3 activation", "

irf3 activation and", "activation and interferon", "and interferon \u03b2", "\u03b2 ifn\u03b2", "ifn\u03b2 production", "production by poly", "by poly i:c", "a synthetic analog", "synthetic analog of", "analog of dsrna", "dsrna are", "are decreased in", "decreased in tbk1", "in tbk1 deficient", "tbk1 deficient mouse", "deficient mouse fibroblasts", "fibroblasts whereas", "whereas normal activation", "normal activation was", "activation was observed", "was observed in", "observed in the", "in the ikbke", "the ikbke deficient", "ikbke deficient fibroblasts.", "deficient fibroblasts. however", "however in", "in double deficient", "double deficient mouse", "fibroblasts the", "of irf3 is", "irf3 is completely", "is completely abolished", "abolished suggesting", "suggesting a partially", "a partially redundant", "partially redundant functions", "redundant functions of", "functions of tbk1", "of tbk1 and", "tbk1 and ikk\u03b5", "hemmi h et", "h et al.", "al. 2004", "2004 .

the", ".

the poly", "

the poly i:c", "i:c induced", "induced phosphorylation of", "phosphorylation of tbk1", "tbk1 and irf3", "and irf3 was", "irf3 was abolished", "was abolished in", "abolished in trif", "trif ticam1", "ticam1 knockout", "knockout human keratinocyte", "human keratinocyte hacat", "keratinocyte hacat cells", "cells bakshi", "bakshi s et", "s et al.", "al. 2017", "2017 . ticam1", ". ticam1 is", "ticam1 is utilized", "is utilized as", "utilized as an", "as an adaptor", "an adaptor protein", "adaptor protein by", "protein by tlr3", "by tlr3 and", "tlr3 and tlr4", "tlr4 yamamoto", "yamamoto m et", "m et al.", "al. 2003", "2003 .

tlr3", ".

tlr3 recruits", "

tlr3 recruits and", "recruits and activates", "and activates pi3", "activates pi3 kinase", "kinase pi3k", "which activates the", "activates the downstream", "the downstream kinase", "kinase akt", "akt leading", "leading to full", "to full phosphorylation", "full phosphorylation and", "phosphorylation and activation", "and activation of", "irf3 sarkar", "sarkar sn et", "sn et al.", "2004 . when", ". when pi3k", "when pi3k is", "pi3k is not", "is not recruited", "not recruited to", "recruited to tlr3", "to tlr3 or", "tlr3 or its", "or its activity", "its activity is", "activity is blocked", "blocked irf3", "irf3 is only", "is only partially", "only partially phosphorylated", "partially phosphorylated and", "phosphorylated and fails", "and fails to", "fails to bind", "to bind the", "bind the promoter", "the promoter of", "promoter of the", "of the target", "the target gene", "gene sarkar", "cell stimulation with viral", "stimulation with viral double", "with viral double stranded", "double stranded ds", "ds rna and", "rna and bacterial lipopolysaccharide", "bacterial lipopolysaccharide lps", "lps activate toll", "activate toll like receptors", "toll like receptors 3", "receptors 3 tlr3", "and tlr4 respectively", "respectively triggering the", "triggering the activation the", "the activation the activation", "activation the activation of", "the activation of two", "activation of two ikk", "of two ikk related", "two ikk related serine/threonine", "ikk related serine/threonine kinases", "serine/threonine kinases tank", "kinases tank binding", "tank binding kinase 1", "kinase 1 tbk1", "tbk1 and i\u03bab", "and i\u03bab kinase \u03b5", "kinase \u03b5 ikk\u03b5", "ikbke which directly", "which directly phosphorylate interferon", "directly phosphorylate interferon regulatory", "phosphorylate interferon regulatory factor", "interferon regulatory factor 3", "factor 3 irf3", "irf3 and irf7", "and irf7 promoting their", "irf7 promoting their dimerization", "promoting their dimerization and", "their dimerization and translocation", "dimerization and translocation into", "and translocation into the", "translocation into the nucleus.", "into the nucleus. although", "the nucleus. although both", "nucleus. although both kinases", "although both kinases show", "both kinases show structural", "kinases show structural and", "show structural and functional", "structural and functional similarities", "functional similarities it", "similarities it seems", "it seems that tbk1", "seems that tbk1 and", "that tbk1 and ikbke", "tbk1 and ikbke differ", "and ikbke differ in", "ikbke differ in their", "differ in their regulation", "in their regulation of", "their regulation of downstream", "regulation of downstream signaling", "of downstream signaling events", "downstream signaling events of", "signaling events of tlr3/tlr4.", "events of tlr3/tlr4.

irf3", "of tlr3/tlr4.

irf3 activation", "tlr3/tlr4.

irf3 activation and", "

irf3 activation and interferon", "activation and interferon \u03b2", "interferon \u03b2 ifn\u03b2", "ifn\u03b2 production by", "production by poly i:c", "i:c a", "a synthetic analog of", "synthetic analog of dsrna", "of dsrna are", "dsrna are decreased", "are decreased in tbk1", "decreased in tbk1 deficient", "in tbk1 deficient mouse", "tbk1 deficient mouse fibroblasts", "mouse fibroblasts whereas", "fibroblasts whereas normal", "whereas normal activation was", "normal activation was observed", "activation was observed in", "was observed in the", "observed in the ikbke", "in the ikbke deficient", "the ikbke deficient fibroblasts.", "ikbke deficient fibroblasts. however", "fibroblasts. however in", "however in double", "in double deficient mouse", "double deficient mouse fibroblasts", "mouse fibroblasts the", "fibroblasts the activation", "the activation of irf3", "activation of irf3 is", "of irf3 is completely", "irf3 is completely abolished", "completely abolished suggesting", "abolished suggesting a", "suggesting a partially redundant", "a partially redundant functions", "partially redundant functions of", "redundant functions of tbk1", "functions of tbk1 and", "of tbk1 and ikk\u03b5", "and ikk\u03b5 ikbke", "ikbke hemmi", "hemmi h et al.", "et al. 2004", "al. 2004 .", "2004 .

the poly", ".

the poly i:c", "poly i:c induced", "i:c induced phosphorylation", "induced phosphorylation of tbk1", "phosphorylation of tbk1 and", "of tbk1 and irf3", "tbk1 and irf3 was", "and irf3 was abolished", "irf3 was abolished in", "was abolished in trif", "in trif ticam1", "ticam1 knockout human", "knockout human keratinocyte hacat", "human keratinocyte hacat cells", "hacat cells bakshi", "cells bakshi s", "bakshi s et al.", "et al. 2017", "al. 2017 .", "2017 . ticam1 is", ". ticam1 is utilized", "ticam1 is utilized as", "is utilized as an", "utilized as an adaptor", "as an adaptor protein", "an adaptor protein by", "adaptor protein by tlr3", "protein by tlr3 and", "by tlr3 and tlr4", "and tlr4 yamamoto", "tlr4 yamamoto m", "yamamoto m et al.", "et al. 2003", "al. 2003 .", "2003 .

tlr3 recruits", ".

tlr3 recruits and", "

tlr3 recruits and activates", "recruits and activates pi3", "and activates pi3 kinase", "pi3 kinase pi3k", "pi3k which", "which activates the downstream", "activates the downstream kinase", "downstream kinase akt", "akt leading to", "leading to full phosphorylation", "to full phosphorylation and", "full phosphorylation and activation", "phosphorylation and activation of", "and activation of irf3", "of irf3 sarkar", "irf3 sarkar sn", "sarkar sn et al.", "2004 . when pi3k", ". when pi3k is", "when pi3k is not", "pi3k is not recruited", "is not recruited to", "not recruited to tlr3", "recruited to tlr3 or", "to tlr3 or its", "tlr3 or its activity", "or its activity is", "its activity is blocked", "is blocked irf3", "blocked irf3 is", "irf3 is only partially", "is only partially phosphorylated", "only partially phosphorylated and", "partially phosphorylated and fails", "phosphorylated and fails to", "and fails to bind", "fails to bind the", "to bind the promoter", "bind the promoter of", "the promoter of the", "promoter of the target", "of the target gene", "target gene sarkar", "gene sarkar sn", "cell stimulation with viral double", "stimulation with viral double stranded", "viral double stranded ds", "stranded ds rna", "ds rna and bacterial", "and bacterial lipopolysaccharide lps", "lipopolysaccharide lps activate", "lps activate toll like", "activate toll like receptors 3", "like receptors 3 tlr3", "3 tlr3 and", "tlr4 respectively triggering", "respectively triggering the activation", "triggering the activation the activation", "the activation the activation of", "activation the activation of two", "the activation of two ikk", "activation of two ikk related", "of two ikk related serine/threonine", "two ikk related serine/threonine kinases", "related serine/threonine kinases tank", "serine/threonine kinases tank binding", "kinases tank binding kinase", "binding kinase 1 tbk1", "1 tbk1 and", "tbk1 and i\u03bab kinase", "i\u03bab kinase \u03b5 ikk\u03b5", "\u03b5 ikk\u03b5 ikbke", "ikk\u03b5 ikbke which", "ikbke which directly phosphorylate", "which directly phosphorylate interferon regulatory", "directly phosphorylate interferon regulatory factor", "phosphorylate interferon regulatory factor 3", "regulatory factor 3 irf3", "3 irf3 and", "irf3 and irf7 promoting", "and irf7 promoting their dimerization", "irf7 promoting their dimerization and", "promoting their dimerization and translocation", "their dimerization and translocation into", "dimerization and translocation into the", "and translocation into the nucleus.", "translocation into the nucleus. although", "into the nucleus. although both", "the nucleus. although both kinases", "nucleus. although both kinases show", "although both kinases show structural", "both kinases show structural and", "kinases show structural and functional", "show structural and functional similarities", "and functional similarities it", "functional similarities it seems", "similarities it seems that", "it seems that tbk1 and", "seems that tbk1 and ikbke", "that tbk1 and ikbke differ", "tbk1 and ikbke differ in", "and ikbke differ in their", "ikbke differ in their regulation", "differ in their regulation of", "in their regulation of downstream", "their regulation of downstream signaling", "regulation of downstream signaling events", "of downstream signaling events of", "downstream signaling events of tlr3/tlr4.", "signaling events of tlr3/tlr4.

irf3", "events of tlr3/tlr4.

irf3 activation", "of tlr3/tlr4.

irf3 activation and", "tlr3/tlr4.

irf3 activation and interferon", "

irf3 activation and interferon \u03b2", "and interferon \u03b2 ifn\u03b2", "\u03b2 ifn\u03b2 production", "ifn\u03b2 production by poly", "poly i:c a", "i:c a synthetic", "a synthetic analog of dsrna", "analog of dsrna are", "of dsrna are decreased", "dsrna are decreased in", "are decreased in tbk1 deficient", "decreased in tbk1 deficient mouse", "in tbk1 deficient mouse fibroblasts", "deficient mouse fibroblasts whereas", "mouse fibroblasts whereas normal", "fibroblasts whereas normal activation", "whereas normal activation was observed", "normal activation was observed in", "activation was observed in the", "was observed in the ikbke", "observed in the ikbke deficient", "in the ikbke deficient fibroblasts.", "the ikbke deficient fibroblasts. however", "deficient fibroblasts. however in", "fibroblasts. however in double", "however in double deficient", "in double deficient mouse fibroblasts", "deficient mouse fibroblasts the", "mouse fibroblasts the activation", "fibroblasts the activation of", "the activation of irf3 is", "activation of irf3 is completely", "of irf3 is completely abolished", "is completely abolished suggesting", "completely abolished suggesting a", "abolished suggesting a partially", "suggesting a partially redundant functions", "a partially redundant functions of", "partially redundant functions of tbk1", "redundant functions of tbk1 and", "functions of tbk1 and ikk\u03b5", "tbk1 and ikk\u03b5 ikbke", "ikbke hemmi h", "h et al. 2004", "et al. 2004 .", "al. 2004 .

the", "2004 .

the poly i:c", "

the poly i:c induced", "poly i:c induced phosphorylation", "i:c induced phosphorylation of", "induced phosphorylation of tbk1 and", "phosphorylation of tbk1 and irf3", "of tbk1 and irf3 was", "tbk1 and irf3 was abolished", "and irf3 was abolished in", "irf3 was abolished in trif", "abolished in trif ticam1", "trif ticam1 knockout", "ticam1 knockout human keratinocyte", "knockout human keratinocyte hacat cells", "keratinocyte hacat cells bakshi", "hacat cells bakshi s", "cells bakshi s et", "s et al. 2017", "et al. 2017 .", "al. 2017 . ticam1", "2017 . ticam1 is utilized", ". ticam1 is utilized as", "ticam1 is utilized as an", "is utilized as an adaptor", "utilized as an adaptor protein", "as an adaptor protein by", "an adaptor protein by tlr3", "adaptor protein by tlr3 and", "protein by tlr3 and tlr4", "tlr3 and tlr4 yamamoto", "and tlr4 yamamoto m", "tlr4 yamamoto m et", "m et al. 2003", "et al. 2003 .", "al. 2003 .

tlr3", "2003 .

tlr3 recruits and", ".

tlr3 recruits and activates", "

tlr3 recruits and activates pi3", "recruits and activates pi3 kinase", "activates pi3 kinase pi3k", "pi3k which activates", "which activates the downstream kinase", "the downstream kinase akt", "kinase akt leading", "akt leading to full", "leading to full phosphorylation and", "to full phosphorylation and activation", "full phosphorylation and activation of", "phosphorylation and activation of irf3", "activation of irf3 sarkar", "of irf3 sarkar sn", "irf3 sarkar sn et", "sn et al. 2004", "al. 2004 . when", "2004 . when pi3k is", ". when pi3k is not", "when pi3k is not recruited", "pi3k is not recruited to", "is not recruited to tlr3", "not recruited to tlr3 or", "recruited to tlr3 or its", "to tlr3 or its activity", "tlr3 or its activity is", "or its activity is blocked", "activity is blocked irf3", "is blocked irf3 is", "blocked irf3 is only", "irf3 is only partially phosphorylated", "is only partially phosphorylated and", "only partially phosphorylated and fails", "partially phosphorylated and fails to", "phosphorylated and fails to bind", "and fails to bind the", "fails to bind the promoter", "to bind the promoter of", "bind the promoter of the", "the promoter of the target", "promoter of the target gene", "the target gene sarkar", "target gene sarkar sn", "gene sarkar sn et" ] }, { "record_id": "GLY_000594_1_685", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "937039", "r hsa", "hsa 937039", "r hsa 937039" ] }, { "record_id": "GLY_000594_1_685", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak1 recruits", "recruits ikk", "ikk complex", "irak1 recruits ikk", "recruits ikk complex", "irak1 recruits ikk complex", "the role", "role of", "of irak1", "irak1 kinase", "kinase activity", "activity in", "in the", "the activation", "activation of", "of nf", "nf kappa", "kappa b", "b by", "by il", "il 1/tlr", "is still", "still uncertain.", "uncertain. it", "it has", "has been", "been shown", "shown that", "that a", "a kinase", "kinase dead", "dead irak1", "irak1 mutants", "mutants can", "can still", "still activate", "activate nf", "kappa b.", "b. furthermore", "stimulation of", "irak1 deficient", "deficient i1a", "i1a 293", "293 cells", "cells with", "with lmp1", "latent membrane", "membrane protein", "protein 1", "a known", "known viral", "viral activator", "activator of", "leads to", "to traf6", "traf6 polyubiquitination", "polyubiquitination and", "and ikkbeta", "ikkbeta activation", "song et", "et al", "al 2006", "2006 .", ". on", "on the", "the other", "other hand", "irak1 enhances", "enhances p65", "p65 ser536", "ser536 phosphorylation", "and p65", "p65 binding", "binding to", "to the", "the promoter", "promoter of", "b dependent", "dependent target", "target genes", "liu g", "g et", "al 2008", "2008 .

", ".

irak1", "irak1 has", "has also", "also been", "shown to", "to be", "be itself", "itself lys63", "lys63 polyubiquitinated", "probably by", "by pellino", "pellino proteins", "which have", "have e3", "e3 ligase", "ligase activity", "activity .", ". mutation", "mutation of", "of the", "the ubiquitination", "ubiquitination sites", "sites on", "on irak1", "irak1 prevented", "prevented interaction", "interaction with", "with the", "the nemo", "nemo subunit", "subunit of", "of ikk", "complex and", "and subsequent", "subsequent il", "1/tlr induced", "induced nf", "b activation", "conze et", "2008 .", ". these", "these data", "data suggest", "suggest that", "that kinase", "activity of", "irak1 is", "is not", "not essential", "essential for", "for its", "its ability", "ability to", "to activate", "while its", "its lys63", "lys63 polyubuquitination", "polyubuquitination allows", "allows irak1", "irak1 to", "to bind", "bind nemo", "nemo thus", "thus facilitating", "facilitating association", "association of", "of traf6", "traf6 and", "and tak1", "tak1 complex", "complex with", "with ikk", "complex followed", "followed by", "by induction", "induction of", "b.

upon", "

upon il", "1/tlr stimulation", "stimulation irak1", "irak1 protein", "protein can", "can undergo", "undergo covalent", "covalent modifications", "modifications including", "including phosphorylation", "kollewe et", "al 2004", "conze db", "db et", "and sumoylation", "huang et", "2004 .", ". depending", "depending upon", "upon the", "the nature", "nature of", "of its", "its modification", "irak1 may", "may perform", "perform distinct", "distinct functions", "functions including", "including activation", "of irf5/7", "uematsu et", "al 2005", "schoenemeyer et", "and stat1/3", "nguyen et", "al 2003", "2003 .", "the role of", "role of irak1", "of irak1 kinase", "irak1 kinase activity", "kinase activity in", "activity in the", "in the activation", "the activation of", "activation of nf", "of nf kappa", "nf kappa b", "kappa b by", "b by il", "by il 1/tlr", "1/tlr is", "is still uncertain.", "still uncertain. it", "uncertain. it has", "it has been", "has been shown", "been shown that", "shown that a", "that a kinase", "a kinase dead", "kinase dead irak1", "dead irak1 mutants", "irak1 mutants can", "mutants can still", "can still activate", "still activate nf", "activate nf kappa", "nf kappa b.", "kappa b. furthermore", "furthermore stimulation", "stimulation of irak1", "of irak1 deficient", "irak1 deficient i1a", "deficient i1a 293", "i1a 293 cells", "293 cells with", "cells with lmp1", "lmp1 latent", "latent membrane protein", "membrane protein 1", "1 a", "a known viral", "known viral activator", "viral activator of", "activator of nf", "b leads", "leads to traf6", "to traf6 polyubiquitination", "traf6 polyubiquitination and", "polyubiquitination and ikkbeta", "and ikkbeta activation", "activation song", "song et al", "et al 2006", "al 2006 .", "2006 . on", ". on the", "on the other", "the other hand", "hand irak1", "irak1 enhances p65", "enhances p65 ser536", "p65 ser536 phosphorylation", "phosphorylation song", "2006 and", "and p65 binding", "p65 binding to", "binding to the", "to the promoter", "the promoter of", "promoter of nf", "kappa b dependent", "b dependent target", "dependent target genes", "genes liu", "liu g et", "g et al", "et al 2008", "al 2008 .

", "2008 .

irak1", ".

irak1 has", "irak1 has also", "has also been", "also been shown", "been shown to", "shown to be", "to be itself", "be itself lys63", "itself lys63 polyubiquitinated", "polyubiquitinated probably", "probably by pellino", "by pellino proteins", "proteins which", "which have e3", "have e3 ligase", "e3 ligase activity", "ligase activity .", "activity . mutation", ". mutation of", "mutation of the", "of the ubiquitination", "the ubiquitination sites", "ubiquitination sites on", "sites on irak1", "on irak1 prevented", "irak1 prevented interaction", "prevented interaction with", "interaction with the", "with the nemo", "the nemo subunit", "nemo subunit of", "subunit of ikk", "of ikk complex", "ikk complex and", "complex and subsequent", "and subsequent il", "subsequent il 1/tlr", "il 1/tlr induced", "1/tlr induced nf", "induced nf kappa", "kappa b activation", "activation conze", "conze et al", "al 2008 .", "2008 . these", ". these data", "these data suggest", "data suggest that", "suggest that kinase", "that kinase activity", "kinase activity of", "activity of irak1", "of irak1 is", "irak1 is not", "is not essential", "not essential for", "essential for its", "for its ability", "its ability to", "ability to activate", "to activate nf", "b while", "while its lys63", "its lys63 polyubuquitination", "lys63 polyubuquitination allows", "polyubuquitination allows irak1", "allows irak1 to", "irak1 to bind", "to bind nemo", "bind nemo thus", "nemo thus facilitating", "thus facilitating association", "facilitating association of", "association of traf6", "of traf6 and", "traf6 and tak1", "and tak1 complex", "tak1 complex with", "complex with ikk", "with ikk complex", "ikk complex followed", "complex followed by", "followed by induction", "by induction of", "induction of nf", "kappa b.

upon", "b.

upon il", "

upon il 1/tlr", "il 1/tlr stimulation", "1/tlr stimulation irak1", "stimulation irak1 protein", "irak1 protein can", "protein can undergo", "can undergo covalent", "undergo covalent modifications", "covalent modifications including", "modifications including phosphorylation", "phosphorylation kollewe", "kollewe et al", "et al 2004", "ubiquitination conze", "conze db et", "db et al", "2008 and", "sumoylation huang", "huang et al", "al 2004 .", "2004 . depending", ". depending upon", "depending upon the", "upon the nature", "the nature of", "nature of its", "of its modification", "modification irak1", "irak1 may perform", "may perform distinct", "perform distinct functions", "distinct functions including", "functions including activation", "including activation of", "activation of irf5/7", "irf5/7 uematsu", "uematsu et al", "et al 2005", "2005 schoenemeyer", "schoenemeyer et al", "b song", "stat1/3 huang", "2004 nguyen", "nguyen et al", "et al 2003", "al 2003 .", "the role of irak1", "role of irak1 kinase", "of irak1 kinase activity", "irak1 kinase activity in", "kinase activity in the", "activity in the activation", "in the activation of", "the activation of nf", "activation of nf kappa", "of nf kappa b", "nf kappa b by", "kappa b by il", "b by il 1/tlr", "il 1/tlr is", "1/tlr is still", "is still uncertain. it", "still uncertain. it has", "uncertain. it has been", "it has been shown", "has been shown that", "been shown that a", "shown that a kinase", "that a kinase dead", "a kinase dead irak1", "kinase dead irak1 mutants", "dead irak1 mutants can", "irak1 mutants can still", "mutants can still activate", "can still activate nf", "still activate nf kappa", "activate nf kappa b.", "nf kappa b. furthermore", "b. furthermore stimulation", "furthermore stimulation of", "stimulation of irak1 deficient", "of irak1 deficient i1a", "irak1 deficient i1a 293", "deficient i1a 293 cells", "i1a 293 cells with", "293 cells with lmp1", "with lmp1 latent", "lmp1 latent membrane", "latent membrane protein 1", "protein 1 a", "1 a known", "a known viral activator", "known viral activator of", "viral activator of nf", "activator of nf kappa", "kappa b leads", "b leads to", "leads to traf6 polyubiquitination", "to traf6 polyubiquitination and", "traf6 polyubiquitination and ikkbeta", "polyubiquitination and ikkbeta activation", "ikkbeta activation song", "activation song et", "song et al 2006", "et al 2006 .", "al 2006 . on", "2006 . on the", ". on the other", "on the other hand", "other hand irak1", "hand irak1 enhances", "irak1 enhances p65 ser536", "enhances p65 ser536 phosphorylation", "ser536 phosphorylation song", "phosphorylation song et", "al 2006 and", "2006 and p65", "and p65 binding to", "p65 binding to the", "binding to the promoter", "to the promoter of", "the promoter of nf", "promoter of nf kappa", "nf kappa b dependent", "kappa b dependent target", "b dependent target genes", "target genes liu", "genes liu g", "liu g et al", "g et al 2008", "et al 2008 .

", "al 2008 .

irak1", "2008 .

irak1 has", ".

irak1 has also", "irak1 has also been", "has also been shown", "also been shown to", "been shown to be", "shown to be itself", "to be itself lys63", "be itself lys63 polyubiquitinated", "lys63 polyubiquitinated probably", "polyubiquitinated probably by", "probably by pellino proteins", "pellino proteins which", "proteins which have", "which have e3 ligase", "have e3 ligase activity", "e3 ligase activity .", "ligase activity . mutation", "activity . mutation of", ". mutation of the", "mutation of the ubiquitination", "of the ubiquitination sites", "the ubiquitination sites on", "ubiquitination sites on irak1", "sites on irak1 prevented", "on irak1 prevented interaction", "irak1 prevented interaction with", "prevented interaction with the", "interaction with the nemo", "with the nemo subunit", "the nemo subunit of", "nemo subunit of ikk", "subunit of ikk complex", "of ikk complex and", "ikk complex and subsequent", "complex and subsequent il", "and subsequent il 1/tlr", "subsequent il 1/tlr induced", "il 1/tlr induced nf", "1/tlr induced nf kappa", "induced nf kappa b", "nf kappa b activation", "b activation conze", "activation conze et", "conze et al 2008", "et al 2008 .", "al 2008 . these", "2008 . these data", ". these data suggest", "these data suggest that", "data suggest that kinase", "suggest that kinase activity", "that kinase activity of", "kinase activity of irak1", "activity of irak1 is", "of irak1 is not", "irak1 is not essential", "is not essential for", "not essential for its", "essential for its ability", "for its ability to", "its ability to activate", "ability to activate nf", "to activate nf kappa", "activate nf kappa b", "kappa b while", "b while its", "while its lys63 polyubuquitination", "its lys63 polyubuquitination allows", "lys63 polyubuquitination allows irak1", "polyubuquitination allows irak1 to", "allows irak1 to bind", "irak1 to bind nemo", "to bind nemo thus", "bind nemo thus facilitating", "nemo thus facilitating association", "thus facilitating association of", "facilitating association of traf6", "association of traf6 and", "of traf6 and tak1", "traf6 and tak1 complex", "and tak1 complex with", "tak1 complex with ikk", "complex with ikk complex", "with ikk complex followed", "ikk complex followed by", "complex followed by induction", "followed by induction of", "by induction of nf", "induction of nf kappa", "of nf kappa b.", "nf kappa b.

upon", "kappa b.

upon il", "b.

upon il 1/tlr", "

upon il 1/tlr stimulation", "il 1/tlr stimulation irak1", "1/tlr stimulation irak1 protein", "stimulation irak1 protein can", "irak1 protein can undergo", "protein can undergo covalent", "can undergo covalent modifications", "undergo covalent modifications including", "covalent modifications including phosphorylation", "including phosphorylation kollewe", "phosphorylation kollewe et", "kollewe et al 2004", "2004 ubiquitination", "ubiquitination conze db", "conze db et al", "db et al 2008", "al 2008 and", "2008 and sumoylation", "and sumoylation huang", "sumoylation huang et", "huang et al 2004", "et al 2004 .", "al 2004 . depending", "2004 . depending upon", ". depending upon the", "depending upon the nature", "upon the nature of", "the nature of its", "nature of its modification", "its modification irak1", "modification irak1 may", "irak1 may perform distinct", "may perform distinct functions", "perform distinct functions including", "distinct functions including activation", "functions including activation of", "including activation of irf5/7", "of irf5/7 uematsu", "irf5/7 uematsu et", "uematsu et al 2005", "al 2005 schoenemeyer", "2005 schoenemeyer et", "schoenemeyer et al 2005", "2005 nf", "kappa b song", "b song et", "and stat1/3 huang", "stat1/3 huang et", "al 2004 nguyen", "2004 nguyen et", "nguyen et al 2003", "et al 2003 .", "the role of irak1 kinase", "role of irak1 kinase activity", "of irak1 kinase activity in", "irak1 kinase activity in the", "kinase activity in the activation", "activity in the activation of", "in the activation of nf", "the activation of nf kappa", "activation of nf kappa b", "of nf kappa b by", "nf kappa b by il", "kappa b by il 1/tlr", "by il 1/tlr is", "il 1/tlr is still", "1/tlr is still uncertain.", "is still uncertain. it has", "still uncertain. it has been", "uncertain. it has been shown", "it has been shown that", "has been shown that a", "been shown that a kinase", "shown that a kinase dead", "that a kinase dead irak1", "a kinase dead irak1 mutants", "kinase dead irak1 mutants can", "dead irak1 mutants can still", "irak1 mutants can still activate", "mutants can still activate nf", "can still activate nf kappa", "still activate nf kappa b.", "activate nf kappa b. furthermore", "kappa b. furthermore stimulation", "b. furthermore stimulation of", "furthermore stimulation of irak1", "stimulation of irak1 deficient i1a", "of irak1 deficient i1a 293", "irak1 deficient i1a 293 cells", "deficient i1a 293 cells with", "i1a 293 cells with lmp1", "cells with lmp1 latent", "with lmp1 latent membrane", "lmp1 latent membrane protein", "membrane protein 1 a", "protein 1 a known", "1 a known viral", "a known viral activator of", "known viral activator of nf", "viral activator of nf kappa", "activator of nf kappa b", "nf kappa b leads", "kappa b leads to", "b leads to traf6", "leads to traf6 polyubiquitination and", "to traf6 polyubiquitination and ikkbeta", "traf6 polyubiquitination and ikkbeta activation", "and ikkbeta activation song", "ikkbeta activation song et", "activation song et al", "song et al 2006 .", "et al 2006 . on", "al 2006 . on the", "2006 . on the other", ". on the other hand", "the other hand irak1", "other hand irak1 enhances", "hand irak1 enhances p65", "irak1 enhances p65 ser536 phosphorylation", "p65 ser536 phosphorylation song", "ser536 phosphorylation song et", "phosphorylation song et al", "et al 2006 and", "al 2006 and p65", "2006 and p65 binding", "and p65 binding to the", "p65 binding to the promoter", "binding to the promoter of", "to the promoter of nf", "the promoter of nf kappa", "promoter of nf kappa b", "of nf kappa b dependent", "nf kappa b dependent target", "kappa b dependent target genes", "dependent target genes liu", "target genes liu g", "genes liu g et", "liu g et al 2008", "g et al 2008 .

", "et al 2008 .

irak1", "al 2008 .

irak1 has", "2008 .

irak1 has also", ".

irak1 has also been", "irak1 has also been shown", "has also been shown to", "also been shown to be", "been shown to be itself", "shown to be itself lys63", "to be itself lys63 polyubiquitinated", "itself lys63 polyubiquitinated probably", "lys63 polyubiquitinated probably by", "polyubiquitinated probably by pellino", "by pellino proteins which", "pellino proteins which have", "proteins which have e3", "which have e3 ligase activity", "have e3 ligase activity .", "e3 ligase activity . mutation", "ligase activity . mutation of", "activity . mutation of the", ". mutation of the ubiquitination", "mutation of the ubiquitination sites", "of the ubiquitination sites on", "the ubiquitination sites on irak1", "ubiquitination sites on irak1 prevented", "sites on irak1 prevented interaction", "on irak1 prevented interaction with", "irak1 prevented interaction with the", "prevented interaction with the nemo", "interaction with the nemo subunit", "with the nemo subunit of", "the nemo subunit of ikk", "nemo subunit of ikk complex", "subunit of ikk complex and", "of ikk complex and subsequent", "ikk complex and subsequent il", "complex and subsequent il 1/tlr", "and subsequent il 1/tlr induced", "subsequent il 1/tlr induced nf", "il 1/tlr induced nf kappa", "1/tlr induced nf kappa b", "induced nf kappa b activation", "kappa b activation conze", "b activation conze et", "activation conze et al", "conze et al 2008 .", "et al 2008 . these", "al 2008 . these data", "2008 . these data suggest", ". these data suggest that", "these data suggest that kinase", "data suggest that kinase activity", "suggest that kinase activity of", "that kinase activity of irak1", "kinase activity of irak1 is", "activity of irak1 is not", "of irak1 is not essential", "irak1 is not essential for", "is not essential for its", "not essential for its ability", "essential for its ability to", "for its ability to activate", "its ability to activate nf", "ability to activate nf kappa", "to activate nf kappa b", "nf kappa b while", "kappa b while its", "b while its lys63", "while its lys63 polyubuquitination allows", "its lys63 polyubuquitination allows irak1", "lys63 polyubuquitination allows irak1 to", "polyubuquitination allows irak1 to bind", "allows irak1 to bind nemo", "irak1 to bind nemo thus", "to bind nemo thus facilitating", "bind nemo thus facilitating association", "nemo thus facilitating association of", "thus facilitating association of traf6", "facilitating association of traf6 and", "association of traf6 and tak1", "of traf6 and tak1 complex", "traf6 and tak1 complex with", "and tak1 complex with ikk", "tak1 complex with ikk complex", "complex with ikk complex followed", "with ikk complex followed by", "ikk complex followed by induction", "complex followed by induction of", "followed by induction of nf", "by induction of nf kappa", "induction of nf kappa b.", "of nf kappa b.

upon", "nf kappa b.

upon il", "kappa b.

upon il 1/tlr", "b.

upon il 1/tlr stimulation", "

upon il 1/tlr stimulation irak1", "il 1/tlr stimulation irak1 protein", "1/tlr stimulation irak1 protein can", "stimulation irak1 protein can undergo", "irak1 protein can undergo covalent", "protein can undergo covalent modifications", "can undergo covalent modifications including", "undergo covalent modifications including phosphorylation", "modifications including phosphorylation kollewe", "including phosphorylation kollewe et", "phosphorylation kollewe et al", "al 2004 ubiquitination", "ubiquitination conze db et", "conze db et al 2008", "et al 2008 and", "al 2008 and sumoylation", "and sumoylation huang et", "sumoylation huang et al", "huang et al 2004 .", "et al 2004 . depending", "al 2004 . depending upon", "2004 . depending upon the", ". depending upon the nature", "depending upon the nature of", "upon the nature of its", "the nature of its modification", "of its modification irak1", "its modification irak1 may", "modification irak1 may perform", "irak1 may perform distinct functions", "may perform distinct functions including", "perform distinct functions including activation", "distinct functions including activation of", "functions including activation of irf5/7", "activation of irf5/7 uematsu", "of irf5/7 uematsu et", "irf5/7 uematsu et al", "et al 2005 schoenemeyer", "al 2005 schoenemeyer et", "2005 schoenemeyer et al", "al 2005 nf", "2005 nf kappa", "nf kappa b song", "kappa b song et", "b song et al", "2006 and stat1/3", "and stat1/3 huang et", "stat1/3 huang et al", "et al 2004 nguyen", "al 2004 nguyen et", "2004 nguyen et al", "nguyen et al 2003 ." ] }, { "record_id": "GLY_000594_1_686", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "937041", "r hsa", "hsa 937041", "r hsa 937041" ] }, { "record_id": "GLY_000594_1_686", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ikk complex", "complex recruitment", "recruitment mediated", "mediated by", "by rip1", "ikk complex recruitment", "complex recruitment mediated", "recruitment mediated by", "mediated by rip1", "ikk complex recruitment mediated", "complex recruitment mediated by", "recruitment mediated by rip1", "ikk complex recruitment mediated by", "complex recruitment mediated by rip1", "receptor interacting", "interacting protein", "protein 1", "mediates the", "the activation", "activation of", "of proinflammatory", "proinflammatory cytokines", "cytokines via", "via intermediate", "intermediate induction", "induction of", "of ikk", "complex in", "in nfkb", "nfkb pathways", "ea et", "et al.", "al. 2006", "2006 .", ". poly", "poly i", "i c", "treatment stimulated", "stimulated the", "the recruitment", "recruitment of", "of rip1", "and tak1", "tak1 to", "to the", "the tlr3", "tlr3 receptor", "receptor complex", "in human", "human embryonic", "embryonic kidney", "kidney hek293", "hek293 transfected", "transfected with", "with flag", "flag tagged", "tagged tlr3", "cusson hermance", 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"GLY_000594_1_687", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "937072", "r hsa", "hsa 937072", "r hsa 937072" ] }, { "record_id": "GLY_000594_1_687", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "traf6 mediated", "mediated induction", "induction of", "of tak1", "tak1 complex", "complex within", "within tlr4", "tlr4 complex", "traf6 mediated induction", "mediated induction of", "induction of tak1", "of tak1 complex", "tak1 complex within", "complex within tlr4", "within tlr4 complex", "traf6 mediated induction of", "mediated induction of tak1", "induction of tak1 complex", "of tak1 complex within", "tak1 complex within tlr4", "complex within tlr4 complex", "traf6 mediated induction of tak1", "mediated induction of tak1 complex", "induction of tak1 complex within", "of tak1 complex within tlr4", "tak1 complex within tlr4 complex", "in human", "together with", "with ubiquitin", "ubiquitin 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tak1", ".

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the", "

the role", "role of", "is somewhat", "somewhat controversial", "controversial and", "and probably", "probably cell", "cell type", "type specific.", "specific. traf6", "traf6 autoubiquitination", "autoubiquitination was", "was found", "found to", "to be", "be dispensable", "dispensable for", "for traf6", "traf6 function", "function to", "to activate", "activate tak1", "tak1 pathway.", "pathway. these", "these findings", "findings are", "are consistent", "consistent with", "with the", "the new", "new mechanism", "mechanism of", "mediated nf", "kb activation", "activation that", "that was", "was suggested", "suggested by", "by xia", "xia et", "et al.", "2009 .", ". traf6", "traf6 generates", "generates unanchored", "unanchored lys63", "linked polyubiquitin", "polyubiquitin chains", "chains that", "that bind", "bind to", "the regulatory", "regulatory subunits", "subunits of", "ikk nemo", "leading to", "of the", "the kinases.

", "kinases.

xia", "demonstrated in", "in vitro", "vitro that", "that unlike", "unlike polyubiquitin", "chains covalently", "covalently attached", "attached to", "to traf6", "traf6 or", "or irak", "tab2 and", "and nemo", "nemo associated", "associated ubiquitin", "ubiquitin chains", "chains were", "were found", "be unanchored", "unanchored and", "and susceptible", "susceptible to", "to n", "n terminal", "terminal ubiquitin", "ubiquitin cleavage.", "cleavage. only", "only k63", "k63 linked", "but not", "not monomeric", "monomeric ubiquitin", "activated tak1", "tak1 in", "in a", "a dose", "dose dependent", "dependent manner.", "manner. optimal", "optimal activation", "the ikk", "ikk complex", "complex was", "was achieved", "achieved using", "using ubiquitin", "ubiquitin polymers", "polymers containing", "containing both", "both k48", "k48 and", "and k63", "k63 linkages.

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tak1", "tak1 .

tak1 phosphorylates", ".

tak1 phosphorylates ikk", "phosphorylates ikk alpha", "ikk alpha and", "alpha and ikk", "and ikk beta", "beta which", "which in turn", "in turn phosphorylate", "turn phosphorylate nf", "phosphorylate nf kb", "nf kb inhibitors", "ikb and", "and eventually results", "eventually results in", "results in ikb", "in ikb degradation", "ikb degradation and", "degradation and nf", "and nf kb", "nf kb translocation", "kb translocation to", "translocation to the", "to the nucleus.", "the nucleus. also", "nucleus. also tak1", "also tak1 mediates", "tak1 mediates jnk", "mediates jnk and", "jnk and p38", "and p38 map", "p38 map kinases", "map kinases activation", "kinases activation by", "activation by phosphorylating", "by phosphorylating mkk4/7", "phosphorylating mkk4/7 and", "mkk4/7 and mkk3/6", "and mkk3/6 respectivly", "mkk3/6 respectivly resulting", "respectivly resulting in", "resulting in the", "in the activation", "the activation of", "activation of many", "of many transcription", "many transcription factors.", "transcription factors.

the", "factors.

the role", "

the role of", "role of traf6", "traf6 is somewhat", "is somewhat controversial", "somewhat controversial and", "controversial and probably", "and probably cell", "probably cell type", "cell type specific.", "type specific. traf6", "specific. traf6 autoubiquitination", "traf6 autoubiquitination was", "autoubiquitination was found", "was found to", "found to be", "to be dispensable", "be dispensable for", "dispensable for traf6", "for traf6 function", "traf6 function to", "function to activate", "to activate tak1", "activate tak1 pathway.", "tak1 pathway. these", "pathway. these findings", "these findings are", "findings are consistent", "are consistent with", "consistent with the", "with the new", "the new mechanism", "new mechanism of", "mechanism of traf6", "of traf6 mediated", "traf6 mediated nf", "mediated nf kb", "nf kb activation", "kb activation that", "activation that was", "that was suggested", "was suggested by", "suggested by xia", "by xia et", "xia et al.", "al. 2009", "2009 . traf6", ". traf6 generates", "traf6 generates unanchored", "generates unanchored lys63", "unanchored lys63 linked", "lys63 linked polyubiquitin", "linked polyubiquitin chains", "polyubiquitin chains that", "chains that bind", "that bind to", "bind to the", "to the regulatory", "the regulatory subunits", "regulatory subunits of", "subunits of tak1", "tak1 tab2", "tab3 and", "and ikk nemo", "leading to the", "to the activation", "activation of the", "of the kinases.

", "the kinases.

xia", "kinases.

xia et", "2009 demonstrated", "demonstrated in vitro", "in vitro that", "vitro that unlike", "that unlike polyubiquitin", "unlike polyubiquitin chains", "polyubiquitin chains covalently", "chains covalently attached", "covalently attached to", "attached to traf6", "to traf6 or", "traf6 or irak", "irak tab2", "tab2 and nemo", "and nemo associated", "nemo associated ubiquitin", "associated ubiquitin chains", "ubiquitin chains were", "chains were found", "were found to", "to be unanchored", "be unanchored and", "unanchored and susceptible", "and susceptible to", "susceptible to n", "to n terminal", "n terminal ubiquitin", "terminal ubiquitin cleavage.", "ubiquitin cleavage. only", "cleavage. only k63", "only k63 linked", "k63 linked polyubiquitin", "chains but", "but not monomeric", "not monomeric ubiquitin", "ubiquitin activated", "activated tak1 in", "tak1 in a", "in a dose", "a dose dependent", "dose dependent manner.", "dependent manner. optimal", "manner. optimal activation", "optimal activation of", "of the ikk", "the ikk complex", "ikk complex was", "complex was achieved", "was achieved using", "achieved using ubiquitin", "using ubiquitin polymers", "ubiquitin polymers containing", "polymers containing both", "containing both k48", "both k48 and", "k48 and k63", "and k63 linkages.

furthermore", "linkages.

furthermore the", "the authors proposed", "authors proposed that", "proposed that the", "that the tak1", "the tak1 complexes", "tak1 complexes might", "complexes might be", "might be brougt", "be brougt in", "brougt in close", "in close proximity", "close proximity by", "proximity by binding", "by binding several", "binding several tab2/3", "several tab2/3 to", "tab2/3 to a", "to a single", "a single polyubiquitin", "single polyubiquitin chain", "polyubiquitin chain to", "chain to facilitate", "to facilitate tak1", "facilitate tak1 kinase", "tak1 kinase trans", "kinase trans phosphorylation.", "trans phosphorylation. alternativly", "alternativly the", "the possibility that", "possibility that polyub", "that polyub binding", "polyub binding promotes", "binding promotes allosteric", "promotes allosteric activation", "allosteric activation of", "activation of tak1", "tak1 complex should", "should be", "considered walsh", "walsh et al", "et al 2008", "al 2008 .", "in human together", "human together with", "together with ubiquitin conjugating", "with ubiquitin conjugating e2", "ubiquitin conjugating e2 type", "conjugating e2 type enzymes", "e2 type enzymes ubc13", "type enzymes ubc13 and", "enzymes ubc13 and uev1a", "and uev1a also", "uev1a also known", "also known as ube2v1", "ube2v1 traf6", "traf6 catalyses lys63 linked", "catalyses lys63 linked ubiquitination.", "lys63 linked ubiquitination. it", "linked ubiquitination. it is", "ubiquitination. it is believed", "it is believed that", "is believed that auto", "believed that auto polyubiquitination", "auto polyubiquitination and", "polyubiquitination and oligomerization", "and oligomerization of traf6", "oligomerization of traf6 is", "of traf6 is followed", "traf6 is followed by", "is followed by binding", "followed by binding the", "by binding the ubiquitin", "binding the ubiquitin receptors", "the ubiquitin receptors of", "ubiquitin receptors of tab2", "receptors of tab2 or", "of tab2 or tab3", "or tab3 tak1", "tab3 tak1 binding", "tak1 binding protein 2", "binding protein 2 and", "protein 2 and 3", "3 which", "which stimulates phosphorylation and", "stimulates phosphorylation and activation", "phosphorylation and activation of", "and activation of tgf", "activation of tgf beta", "of tgf beta activated", "tgf beta activated kinase", "beta activated kinase 1", "activated kinase 1 tak1", "kinase 1 tak1 .

tak1", "1 tak1 .

tak1 phosphorylates", "tak1 .

tak1 phosphorylates ikk", ".

tak1 phosphorylates ikk alpha", "phosphorylates ikk alpha and", "ikk alpha and ikk", "alpha and ikk beta", "ikk beta which", "beta which in", "which in turn phosphorylate", "in turn phosphorylate nf", "turn phosphorylate nf kb", "phosphorylate nf kb inhibitors", "inhibitors ikb", "ikb and eventually", "and eventually results in", "eventually results in ikb", "results in ikb degradation", "in ikb degradation and", "ikb degradation and nf", "degradation and nf kb", "and nf kb translocation", "nf kb translocation to", "kb translocation to the", "translocation to the nucleus.", "to the nucleus. also", "the nucleus. also tak1", "nucleus. also tak1 mediates", "also tak1 mediates jnk", "tak1 mediates jnk and", "mediates jnk and p38", "jnk and p38 map", "and p38 map kinases", "p38 map kinases activation", "map kinases activation by", "kinases activation by phosphorylating", "activation by phosphorylating mkk4/7", "by phosphorylating mkk4/7 and", "phosphorylating mkk4/7 and mkk3/6", "mkk4/7 and mkk3/6 respectivly", "and mkk3/6 respectivly resulting", "mkk3/6 respectivly resulting in", "respectivly resulting in the", "resulting in the activation", "in the activation of", "the activation of many", "activation of many transcription", "of many transcription factors.", "many transcription factors.

the", "transcription factors.

the role", "factors.

the role of", "

the role of traf6", "role of traf6 is", "of traf6 is somewhat", "traf6 is somewhat controversial", "is somewhat controversial and", "somewhat controversial and probably", "controversial and probably cell", "and probably cell type", "probably cell type specific.", "cell type specific. traf6", "type specific. traf6 autoubiquitination", "specific. traf6 autoubiquitination was", "traf6 autoubiquitination was found", "autoubiquitination was found to", "was found to be", "found to be dispensable", "to be dispensable for", "be dispensable for traf6", "dispensable for traf6 function", "for traf6 function to", "traf6 function to activate", "function to activate tak1", "to activate tak1 pathway.", "activate tak1 pathway. these", "tak1 pathway. these findings", "pathway. these findings are", "these findings are consistent", "findings are consistent with", "are consistent with the", "consistent with the new", "with the new mechanism", "the new mechanism of", "new mechanism of traf6", "mechanism of traf6 mediated", "of traf6 mediated nf", "traf6 mediated nf kb", "mediated nf kb activation", "nf kb activation that", "kb activation that was", "activation that was suggested", "that was suggested by", "was suggested by xia", "suggested by xia et", "by xia et al.", "et al. 2009", "al. 2009 .", "2009 . traf6 generates", ". traf6 generates unanchored", "traf6 generates unanchored lys63", "generates unanchored lys63 linked", "unanchored lys63 linked polyubiquitin", "lys63 linked polyubiquitin chains", "linked polyubiquitin chains that", "polyubiquitin chains that bind", "chains that bind to", "that bind to the", "bind to the regulatory", "to the regulatory subunits", "the regulatory subunits of", "regulatory subunits of tak1", "of tak1 tab2", "tak1 tab2 or", "or tab3 and", "tab3 and ikk", "nemo leading", "leading to the activation", "to the activation of", "the activation of the", "activation of the kinases.

", "of the kinases.

xia", "the kinases.

xia et", "kinases.

xia et al.", "2009 demonstrated in", "demonstrated in vitro that", "in vitro that unlike", "vitro that unlike polyubiquitin", "that unlike polyubiquitin chains", "unlike polyubiquitin chains covalently", "polyubiquitin chains covalently attached", "chains covalently attached to", "covalently attached to traf6", "attached to traf6 or", "to traf6 or irak", "or irak tab2", "irak tab2 and", "tab2 and nemo associated", "and nemo associated ubiquitin", "nemo associated ubiquitin chains", "associated ubiquitin chains were", "ubiquitin chains were found", "chains were found to", "were found to be", "found to be unanchored", "to be unanchored and", "be unanchored and susceptible", "unanchored and susceptible to", "and susceptible to n", "susceptible to n terminal", "to n terminal ubiquitin", "n terminal ubiquitin cleavage.", "terminal ubiquitin cleavage. only", "ubiquitin cleavage. only k63", "cleavage. only k63 linked", "only k63 linked polyubiquitin", "k63 linked polyubiquitin chains", "polyubiquitin chains but", "chains but not", "but not monomeric ubiquitin", "monomeric ubiquitin activated", "ubiquitin activated tak1", "activated tak1 in a", "tak1 in a dose", "in a dose dependent", "a dose dependent manner.", "dose dependent manner. optimal", "dependent manner. optimal activation", "manner. optimal activation of", "optimal activation of the", "activation of the ikk", "of the ikk complex", "the ikk complex was", "ikk complex was achieved", "complex was achieved using", "was achieved using ubiquitin", "achieved using ubiquitin polymers", "using ubiquitin polymers containing", "ubiquitin polymers containing both", "polymers containing both k48", "containing both k48 and", "both k48 and k63", "k48 and k63 linkages.

furthermore", "k63 linkages.

furthermore the", "linkages.

furthermore the authors", "the authors proposed that", "authors proposed that the", "proposed that the tak1", "that the tak1 complexes", "the tak1 complexes might", "tak1 complexes might be", "complexes might be brougt", "might be brougt in", "be brougt in close", "brougt in close proximity", "in close proximity by", "close proximity by binding", "proximity by binding several", "by binding several tab2/3", "binding several tab2/3 to", "several tab2/3 to a", "tab2/3 to a single", "to a single polyubiquitin", "a single polyubiquitin chain", "single polyubiquitin chain to", "polyubiquitin chain to facilitate", "chain to facilitate tak1", "to facilitate tak1 kinase", "facilitate tak1 kinase trans", "tak1 kinase trans phosphorylation.", "kinase trans phosphorylation. alternativly", "phosphorylation. alternativly the", "alternativly the possibility", "the possibility that polyub", "possibility that polyub binding", "that polyub binding promotes", "polyub binding promotes allosteric", "binding promotes allosteric activation", "promotes allosteric activation of", "allosteric activation of tak1", "activation of tak1 complex", "of tak1 complex should", "complex should be", "should be considered", "be considered walsh", "considered walsh et", "walsh et al 2008", "et al 2008 .", "in human together with", "human together with ubiquitin", "together with ubiquitin conjugating e2", "with ubiquitin conjugating e2 type", "ubiquitin conjugating e2 type enzymes", "conjugating e2 type enzymes ubc13", "e2 type enzymes ubc13 and", "type enzymes ubc13 and uev1a", "ubc13 and uev1a also", "and uev1a also known", "uev1a also known as", "as ube2v1 traf6", "ube2v1 traf6 catalyses", "traf6 catalyses lys63 linked ubiquitination.", "catalyses lys63 linked ubiquitination. it", "lys63 linked ubiquitination. it is", "linked ubiquitination. it is believed", "ubiquitination. it is believed that", "it is believed that auto", "is believed that auto polyubiquitination", "that auto polyubiquitination and", "auto polyubiquitination and oligomerization", "polyubiquitination and oligomerization of", "and oligomerization of traf6 is", "oligomerization of traf6 is followed", "of traf6 is followed by", "traf6 is followed by binding", "is followed by binding the", "followed by binding the ubiquitin", "by binding the ubiquitin receptors", "binding the ubiquitin receptors of", "the ubiquitin receptors of tab2", "ubiquitin receptors of tab2 or", "receptors of tab2 or tab3", "tab2 or tab3 tak1", "or tab3 tak1 binding", "tab3 tak1 binding protein", "tak1 binding protein 2 and", "binding protein 2 and 3", "and 3 which", "3 which stimulates", "which stimulates phosphorylation and activation", "stimulates phosphorylation and activation of", "phosphorylation and activation of tgf", "and activation of tgf beta", "activation of tgf beta activated", "of tgf beta activated kinase", "tgf beta activated kinase 1", "beta activated kinase 1 tak1", "activated kinase 1 tak1 .

tak1", "kinase 1 tak1 .

tak1 phosphorylates", "1 tak1 .

tak1 phosphorylates ikk", "tak1 .

tak1 phosphorylates ikk alpha", ".

tak1 phosphorylates ikk alpha and", "phosphorylates ikk alpha and ikk", "ikk alpha and ikk beta", "and ikk beta which", "ikk beta which in", "beta which in turn", "which in turn phosphorylate nf", "in turn phosphorylate nf kb", "turn phosphorylate nf kb inhibitors", "kb inhibitors ikb", "ikb and eventually results", "and eventually results in ikb", "eventually results in ikb degradation", "results in ikb degradation and", "in ikb degradation and nf", "ikb degradation and nf kb", "degradation and nf kb translocation", "and nf kb translocation to", "nf kb translocation to the", "kb translocation to the nucleus.", "translocation to the nucleus. also", "to the nucleus. also tak1", "the nucleus. also tak1 mediates", "nucleus. also tak1 mediates jnk", "also tak1 mediates jnk and", "tak1 mediates jnk and p38", "mediates jnk and p38 map", "jnk and p38 map kinases", "and p38 map kinases activation", "p38 map kinases activation by", "map kinases activation by phosphorylating", "kinases activation by phosphorylating mkk4/7", "activation by phosphorylating mkk4/7 and", "by phosphorylating mkk4/7 and mkk3/6", "phosphorylating mkk4/7 and mkk3/6 respectivly", "mkk4/7 and mkk3/6 respectivly resulting", "and mkk3/6 respectivly resulting in", "mkk3/6 respectivly resulting in the", "respectivly resulting in the activation", "resulting in the activation of", "in the activation of many", "the activation of many transcription", "activation of many transcription factors.", "of many transcription factors.

the", "many transcription factors.

the role", "transcription factors.

the role of", "factors.

the role of traf6", "

the role of traf6 is", "role of traf6 is somewhat", "of traf6 is somewhat controversial", "traf6 is somewhat controversial and", "is somewhat controversial and probably", "somewhat controversial and probably cell", "controversial and probably cell type", "and probably cell type specific.", "probably cell type specific. traf6", "cell type specific. traf6 autoubiquitination", "type specific. traf6 autoubiquitination was", "specific. traf6 autoubiquitination was found", "traf6 autoubiquitination was found to", "autoubiquitination was found to be", "was found to be dispensable", "found to be dispensable for", "to be dispensable for traf6", "be dispensable for traf6 function", "dispensable for traf6 function to", "for traf6 function to activate", "traf6 function to activate tak1", "function to activate tak1 pathway.", "to activate tak1 pathway. these", "activate tak1 pathway. these findings", "tak1 pathway. these findings are", "pathway. these findings are consistent", "these findings are consistent with", "findings are consistent with the", "are consistent with the new", "consistent with the new mechanism", "with the new mechanism of", "the new mechanism of traf6", "new mechanism of traf6 mediated", "mechanism of traf6 mediated nf", "of traf6 mediated nf kb", "traf6 mediated nf kb activation", "mediated nf kb activation that", "nf kb activation that was", "kb activation that was suggested", "activation that was suggested by", "that was suggested by xia", "was suggested by xia et", "suggested by xia et al.", "xia et al. 2009", "et al. 2009 .", "al. 2009 . traf6", "2009 . traf6 generates unanchored", ". traf6 generates unanchored lys63", "traf6 generates unanchored lys63 linked", "generates unanchored lys63 linked polyubiquitin", "unanchored lys63 linked polyubiquitin chains", "lys63 linked polyubiquitin chains that", "linked polyubiquitin chains that bind", "polyubiquitin chains that bind to", "chains that bind to the", "that bind to the regulatory", "bind to the regulatory subunits", "to the regulatory subunits of", "the regulatory subunits of tak1", "subunits of tak1 tab2", "of tak1 tab2 or", "tak1 tab2 or tab3", "tab2 or tab3 and", "or tab3 and ikk", "tab3 and ikk nemo", "ikk nemo leading", "nemo leading to", "leading to the activation of", "to the activation of the", "the activation of the kinases.

", "activation of the kinases.

xia", "of the kinases.

xia et", "the kinases.

xia et al.", "al. 2009 demonstrated", "2009 demonstrated in vitro", "demonstrated in vitro that unlike", "in vitro that unlike polyubiquitin", "vitro that unlike polyubiquitin chains", "that unlike polyubiquitin chains covalently", "unlike polyubiquitin chains covalently attached", "polyubiquitin chains covalently attached to", "chains covalently attached to traf6", "covalently attached to traf6 or", "attached to traf6 or irak", "traf6 or irak tab2", "or irak tab2 and", "irak tab2 and nemo", "tab2 and nemo associated ubiquitin", "and nemo associated ubiquitin chains", "nemo associated ubiquitin chains were", "associated ubiquitin chains were found", "ubiquitin chains were found to", "chains were found to be", "were found to be unanchored", "found to be unanchored and", "to be unanchored and susceptible", "be unanchored and susceptible to", "unanchored and susceptible to n", "and susceptible to n terminal", "susceptible to n terminal ubiquitin", "to n terminal ubiquitin cleavage.", "n terminal ubiquitin cleavage. only", "terminal ubiquitin cleavage. only k63", "ubiquitin cleavage. only k63 linked", "cleavage. only k63 linked polyubiquitin", "only k63 linked polyubiquitin chains", "linked polyubiquitin chains but", "polyubiquitin chains but not", "chains but not monomeric", "not monomeric ubiquitin activated", "monomeric ubiquitin activated tak1", "ubiquitin activated tak1 in", "activated tak1 in a dose", "tak1 in a dose dependent", "in a dose dependent manner.", "a dose dependent manner. optimal", "dose dependent manner. optimal activation", "dependent manner. optimal activation of", "manner. optimal activation of the", "optimal activation of the ikk", "activation of the ikk complex", "of the ikk complex was", "the ikk complex was achieved", "ikk complex was achieved using", "complex was achieved using ubiquitin", "was achieved using ubiquitin polymers", "achieved using ubiquitin polymers containing", "using ubiquitin polymers containing both", "ubiquitin polymers containing both k48", "polymers containing both k48 and", "containing both k48 and k63", "both k48 and k63 linkages.

furthermore", "and k63 linkages.

furthermore the", "k63 linkages.

furthermore the authors", "linkages.

furthermore the authors proposed", "the authors proposed that the", "authors proposed that the tak1", "proposed that the tak1 complexes", "that the tak1 complexes might", "the tak1 complexes might be", "tak1 complexes might be brougt", "complexes might be brougt in", "might be brougt in close", "be brougt in close proximity", "brougt in close proximity by", "in close proximity by binding", "close proximity by binding several", "proximity by binding several tab2/3", "by binding several tab2/3 to", "binding several tab2/3 to a", "several tab2/3 to a single", "tab2/3 to a single polyubiquitin", "to a single polyubiquitin chain", "a single polyubiquitin chain to", "single polyubiquitin chain to facilitate", "polyubiquitin chain to facilitate tak1", "chain to facilitate tak1 kinase", "to facilitate tak1 kinase trans", "facilitate tak1 kinase trans phosphorylation.", "tak1 kinase trans phosphorylation. alternativly", "trans phosphorylation. alternativly the", "phosphorylation. alternativly the possibility", "alternativly the possibility that", "the possibility that polyub binding", "possibility that polyub binding promotes", "that polyub binding promotes allosteric", "polyub binding promotes allosteric activation", "binding promotes allosteric activation of", "promotes allosteric activation of tak1", "allosteric activation of tak1 complex", "activation of tak1 complex should", "tak1 complex should be", "complex should be considered", "be considered walsh et", "considered walsh et al", "walsh et al 2008 ." ] }, { "record_id": "GLY_000594_1_688", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9603798", "r hsa", "hsa 9603798", "r hsa 9603798" ] }, { "record_id": "GLY_000594_1_688", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "class i", "i peroxisomal", "peroxisomal membrane", "membrane protein", "protein import", "class i peroxisomal", "i peroxisomal membrane", "peroxisomal membrane protein", "membrane protein import", "class i peroxisomal membrane", "i peroxisomal membrane protein", "peroxisomal membrane protein import", "class i peroxisomal membrane protein", "i peroxisomal membrane protein import", "most peroxisomal", "membrane proteins", "are inserted", "inserted into", "into the", "the peroxisomal", "membrane by", "by the", "the receptor", "receptor chaperone", "chaperone pex19", "pex19 and", "and the", "the docking", "docking receptor", "receptor pex3", "soukupova et", "et al.", "al. 1999", "muntau et", "al. 2003", "fang et", "al. 2004", "fujiki et", "al. 2006", "matsuzono and", "and fujiki", "fujiki 2006", "matsuzono et", "pinto et", "sato et", "al. 2008", "al. 2010", "schmidt et", "hattula et", "al. 2014", "reviewed in", "in fujiki", "mayerhofer 2016", "2016 .", ". pex19", "pex19 binds", "binds the", "the pmp", "pmp as", "as it", "it is", "is translated", "translated in", "in the", "the cytosol.", "cytosol. recognition", "recognition of", "of the", "pmp by", "by pex", "pex 19", "19 appears", "appears to", "to depend", "depend on", "on positively", "positively charged", "charged residues", "residues in", "the transmembrane", "transmembrane domain", "domain of", "costello et", "al. 2017", "2017 .", ". the", "the pex19:pmp", "pex19:pmp complex", "complex then", "then interacts", "interacts with", "with pex3", "pex3 located", "located in", "peroxisomal membrane.", "membrane. through", "through a", "a mechanism", "mechanism that", "that is", "is not", "not yet", "yet clear", "pmp is", "is inserted", "membrane and", "and pex19", "pex19 dissociates", "dissociates from", "from pex3.", "pex3. a", "a current", "current model", "model involves", "involves transfer", "transfer of", "pmp from", "from pex19", "pex19 to", "to a", "a hydrophobic", "hydrophobic region", "region of", "of pex3", "pex3 followed", "followed by", "by insertion", "insertion of", "pmp into", "the membrane", "chen et", "reviewed by", "by giannopoulou", "giannopoulou et", "al. 2016", "the process", "process does", "does not", "not appear", "appear to", "to require", "require hydrolysis", "hydrolysis of", "of atp", "atp or", "or gtp", "2006 .
unlike", ".
unlike other", "other pmps", "pex3 is", "by binding", "binding pex19", "and then", "then docking", "docking with", "with pex16", "matsuzaki and", "fujiki 2008", "2008 .", ". both", "both pex3", "pex3 and", "and pex16", "pex16 can", "can also", "also be", "be co", "co translationally", "translationally inserted", "the endoplasmic", "endoplasmic reticulum", "reticulum membrane", "kim et", "yonekawa et", "al. 2011", "aranovich et", "hua et", "al. 2015", "mayerhofer et", ". this", "this region", "the er", "er membrane", "membrane then", "then buds", "buds to", "to contribute", "contribute to", "to new", "new peroxisomes.", "peroxisomes. pex3", "is also", "also observed", "observed to", "to insert", "insert into", "the mitochondrial", "mitochondrial outer", "outer membrane", "sugiura et", ". regions", "regions of", "and mitochondrial", "membrane are", "are then", "then released", "released to", "to form", "form pre", "pre peroxisomal", "peroxisomal vesicles", "vesicles which", "which fuse", "fuse to", "form new", "new peroxisomes", ". peroxisomes", "peroxisomes therefore", "therefore appear", "to arise", "arise from", "from fission", "fission of", "of existing", "existing peroxisomes", "peroxisomes and", "and production", "production of", "of new", "peroxisomes from", "from precursors", "precursors derived", "derived from", "from mitochondria", "mitochondria and", "hua and", "and kim", "kim 2016", "most peroxisomal membrane", "peroxisomal membrane proteins", "proteins pmps", "pmps are", "are inserted into", "inserted into the", "into the peroxisomal", "the peroxisomal membrane", "peroxisomal membrane by", "membrane by the", "by the receptor", "the receptor chaperone", "receptor chaperone pex19", "chaperone pex19 and", "pex19 and the", "and the docking", "the docking receptor", "docking receptor pex3", "pex3 soukupova", "soukupova et al.", "et al. 1999", "1999 muntau", "muntau et al.", "et al. 2003", "2003 fang", "fang et al.", "et al. 2004", "2004 fujiki", "fujiki et al.", "et al. 2006", "2006 matsuzono", "matsuzono and fujiki", "and fujiki 2006", "matsuzono et al.", "2006 pinto", "pinto et al.", "2006 sato", "sato et al.", "et al. 2008", "2008 sato", "et al. 2010", "2010 schmidt", "schmidt et al.", "2010 hattula", "hattula et al.", "et al. 2014", "2014 reviewed", "reviewed in fujiki", "in fujiki et", "2014 mayerhofer", "mayerhofer 2016 .", "2016 . pex19", ". pex19 binds", "pex19 binds the", "binds the pmp", "the pmp as", "pmp as it", "as it is", "it is translated", "is translated in", "translated in the", "in the cytosol.", "the cytosol. recognition", "cytosol. recognition of", "recognition of the", "of the pmp", "the pmp by", "pmp by pex", "by pex 19", "pex 19 appears", "19 appears to", "appears to depend", "to depend on", "depend on positively", "on positively charged", "positively charged residues", "charged residues in", "residues in the", "in the transmembrane", "the transmembrane domain", "transmembrane domain of", "domain of the", "pmp costello", "costello et al.", "et al. 2017", "al. 2017 .", "2017 . the", ". the pex19:pmp", "the pex19:pmp complex", "pex19:pmp complex then", "complex then interacts", "then interacts with", "interacts with pex3", "with pex3 located", "pex3 located in", "located in the", "in the peroxisomal", "the peroxisomal membrane.", "peroxisomal membrane. through", "membrane. through a", "through a mechanism", "a mechanism that", "mechanism that is", "that is not", "is not yet", "not yet clear", "clear the", "the pmp is", "pmp is inserted", "is inserted into", "peroxisomal membrane and", "membrane and pex19", "and pex19 dissociates", "pex19 dissociates from", "dissociates from pex3.", "from pex3. a", "pex3. a current", "a current model", "current model involves", "model involves transfer", "involves transfer of", "transfer of the", "the pmp from", "pmp from pex19", "from pex19 to", "pex19 to a", "to a hydrophobic", "a hydrophobic region", "hydrophobic region of", "region of pex3", "of pex3 followed", "pex3 followed by", "followed by insertion", "by insertion of", "insertion of the", "the pmp into", "pmp into the", "into the membrane", "membrane chen", "chen et al.", "reviewed by giannopoulou", "by giannopoulou et", "giannopoulou et al.", "et al. 2016", "al. 2016 .", "2016 . the", ". the process", "the process does", "process does not", "does not appear", "not appear to", "appear to require", "to require hydrolysis", "require hydrolysis of", "hydrolysis of atp", "of atp or", "atp or gtp", "gtp pinto", "al. 2006 .
unlike", "2006 .
unlike other", ".
unlike other pmps", "pmps pex3", "pex3 is inserted", "membrane by binding", "by binding pex19", "binding pex19 and", "pex19 and then", "and then docking", "then docking with", "docking with pex16", "pex16 matsuzaki", "matsuzaki and fujiki", "and fujiki 2008", "fujiki 2008 .", "2008 . both", ". both pex3", "both pex3 and", "pex3 and pex16", "and pex16 can", "pex16 can also", "can also be", "also be co", "be co translationally", "co translationally inserted", "translationally inserted into", "into the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum membrane", "membrane kim", "kim et al.", "2006 yonekawa", "yonekawa et al.", "et al. 2011", "2011 aranovich", "aranovich et al.", "2014 hua", "hua et al.", "et al. 2015", "2015 mayerhofer", "mayerhofer et al.", "2016 . this", ". this region", "this region of", "region of the", "of the er", "the er membrane", "er membrane then", "membrane then buds", "then buds to", "buds to contribute", "to contribute to", "contribute to new", "to new peroxisomes.", "new peroxisomes. pex3", "peroxisomes. pex3 is", "pex3 is also", "is also observed", "also observed to", "observed to insert", "to insert into", "insert into the", "into the mitochondrial", "the mitochondrial outer", "mitochondrial outer membrane", "membrane sugiura", "sugiura et al.", "2017 . regions", ". regions of", "regions of the", "er membrane and", "membrane and mitochondrial", "and mitochondrial outer", "outer membrane are", "membrane are then", "are then released", "then released to", "released to form", "to form pre", "form pre peroxisomal", "pre peroxisomal vesicles", "peroxisomal vesicles which", "vesicles which fuse", "which fuse to", "fuse to form", "to form new", "form new peroxisomes", "peroxisomes sugiura", "2017 . peroxisomes", ". peroxisomes therefore", "peroxisomes therefore appear", "therefore appear to", "appear to arise", "to arise from", "arise from fission", "from fission of", "fission of existing", "of existing peroxisomes", "existing peroxisomes and", "peroxisomes and production", "and production of", "production of new", "of new peroxisomes", "new peroxisomes from", "peroxisomes from precursors", "from precursors derived", "precursors derived from", "derived from mitochondria", "from mitochondria and", "mitochondria and the", "and the er", "er sugiura", "2017 reviewed", "hua and kim", "and kim 2016", "kim 2016 .", "most peroxisomal membrane proteins", "membrane proteins pmps", "pmps are inserted", "are inserted into the", "inserted into the peroxisomal", "into the peroxisomal membrane", "the peroxisomal membrane by", "peroxisomal membrane by the", "membrane by the receptor", "by the receptor chaperone", "the receptor chaperone pex19", "receptor chaperone pex19 and", "chaperone pex19 and the", "pex19 and the docking", "and the docking receptor", "the docking receptor pex3", "receptor pex3 soukupova", "pex3 soukupova et", "soukupova et al. 1999", "al. 1999 muntau", "1999 muntau et", "muntau et al. 2003", "al. 2003 fang", "2003 fang et", "fang et al. 2004", "al. 2004 fujiki", "2004 fujiki et", "fujiki et al. 2006", "al. 2006 matsuzono", "2006 matsuzono and", "matsuzono and fujiki 2006", "fujiki 2006 matsuzono", "2006 matsuzono et", "matsuzono et al. 2006", "al. 2006 pinto", "2006 pinto et", "pinto et al. 2006", "al. 2006 sato", "2006 sato et", "sato et al. 2008", "al. 2008 sato", "2008 sato et", "sato et al. 2010", "al. 2010 schmidt", "2010 schmidt et", "schmidt et al. 2010", "al. 2010 hattula", "2010 hattula et", "hattula et al. 2014", "al. 2014 reviewed", "2014 reviewed in", "reviewed in fujiki et", "in fujiki et al.", "fujiki et al. 2014", "al. 2014 mayerhofer", "2014 mayerhofer 2016", "mayerhofer 2016 . pex19", "2016 . pex19 binds", ". pex19 binds the", "pex19 binds the pmp", "binds the pmp as", "the pmp as it", "pmp as it is", "as it is translated", "it is translated in", "is translated in the", "translated in the cytosol.", "in the cytosol. recognition", "the cytosol. recognition of", "cytosol. recognition of the", "recognition of the pmp", "of the pmp by", "the pmp by pex", "pmp by pex 19", "by pex 19 appears", "pex 19 appears to", "19 appears to depend", "appears to depend on", "to depend on positively", "depend on positively charged", "on positively charged residues", "positively charged residues in", "charged residues in the", "residues in the transmembrane", "in the transmembrane domain", "the transmembrane domain of", "transmembrane domain of the", "domain of the pmp", "the pmp costello", "pmp costello et", "costello et al. 2017", "et al. 2017 .", "al. 2017 . the", "2017 . the pex19:pmp", ". the pex19:pmp complex", "the pex19:pmp complex then", "pex19:pmp complex then interacts", "complex then interacts with", "then interacts with pex3", "interacts with pex3 located", "with pex3 located in", "pex3 located in the", "located in the peroxisomal", "in the peroxisomal membrane.", "the peroxisomal membrane. through", "peroxisomal membrane. through a", "membrane. through a mechanism", "through a mechanism that", "a mechanism that is", "mechanism that is not", "that is not yet", "is not yet clear", "yet clear the", "clear the pmp", "the pmp is inserted", "pmp is inserted into", "is inserted into the", "the peroxisomal membrane and", "peroxisomal membrane and pex19", "membrane and pex19 dissociates", "and pex19 dissociates from", "pex19 dissociates from pex3.", "dissociates from pex3. a", "from pex3. a current", "pex3. a current model", "a current model involves", "current model involves transfer", "model involves transfer of", "involves transfer of the", "transfer of the pmp", "of the pmp from", "the pmp from pex19", "pmp from pex19 to", "from pex19 to a", "pex19 to a hydrophobic", "to a hydrophobic region", "a hydrophobic region of", "hydrophobic region of pex3", "region of pex3 followed", "of pex3 followed by", "pex3 followed by insertion", "followed by insertion of", "by insertion of the", "insertion of the pmp", "of the pmp into", "the pmp into the", "pmp into the membrane", "the membrane chen", "membrane chen et", "chen et al. 2014", "2014 reviewed by", "reviewed by giannopoulou et", "by giannopoulou et al.", "giannopoulou et al. 2016", "et al. 2016 .", "al. 2016 . the", "2016 . the process", ". the process does", "the process does not", "process does not appear", "does not appear to", "not appear to require", "appear to require hydrolysis", "to require hydrolysis of", "require hydrolysis of atp", "hydrolysis of atp or", "of atp or gtp", "or gtp pinto", "gtp pinto et", "et al. 2006 .
unlike", "al. 2006 .
unlike other", "2006 .
unlike other pmps", "other pmps pex3", "pmps pex3 is", "pex3 is inserted into", "peroxisomal membrane by binding", "membrane by binding pex19", "by binding pex19 and", "binding pex19 and then", "pex19 and then docking", "and then docking with", "then docking with pex16", "with pex16 matsuzaki", "pex16 matsuzaki and", "matsuzaki and fujiki 2008", "and fujiki 2008 .", "fujiki 2008 . both", "2008 . both pex3", ". both pex3 and", "both pex3 and pex16", "pex3 and pex16 can", "and pex16 can also", "pex16 can also be", "can also be co", "also be co translationally", "be co translationally inserted", "co translationally inserted into", "translationally inserted into the", "inserted into the endoplasmic", "into the endoplasmic reticulum", "the endoplasmic reticulum membrane", "reticulum membrane kim", "membrane kim et", "kim et al. 2006", "al. 2006 yonekawa", "2006 yonekawa et", "yonekawa et al. 2011", "al. 2011 aranovich", "2011 aranovich et", "aranovich et al. 2014", "al. 2014 hua", "2014 hua et", "hua et al. 2015", "al. 2015 mayerhofer", "2015 mayerhofer et", "mayerhofer et al. 2016", "al. 2016 . this", "2016 . this region", ". this region of", "this region of the", "region of the er", "of the er membrane", "the er membrane then", "er membrane then buds", "membrane then buds to", "then buds to contribute", "buds to contribute to", "to contribute to new", "contribute to new peroxisomes.", "to new peroxisomes. pex3", "new peroxisomes. pex3 is", "peroxisomes. pex3 is also", "pex3 is also observed", "is also observed to", "also observed to insert", "observed to insert into", "to insert into the", "insert into the mitochondrial", "into the mitochondrial outer", "the mitochondrial outer membrane", "outer membrane sugiura", "membrane sugiura et", "sugiura et al. 2017", "al. 2017 . regions", "2017 . regions of", ". regions of the", "regions of the er", "the er membrane and", "er membrane and mitochondrial", "membrane and mitochondrial outer", "and mitochondrial outer membrane", "mitochondrial outer membrane are", "outer membrane are then", "membrane are then released", "are then released to", "then released to form", "released to form pre", "to form pre peroxisomal", "form pre peroxisomal vesicles", "pre peroxisomal vesicles which", "peroxisomal vesicles which fuse", "vesicles which fuse to", "which fuse to form", "fuse to form new", "to form new peroxisomes", "new peroxisomes sugiura", "peroxisomes sugiura et", "al. 2017 . peroxisomes", "2017 . peroxisomes therefore", ". peroxisomes therefore appear", "peroxisomes therefore appear to", "therefore appear to arise", "appear to arise from", "to arise from fission", "arise from fission of", "from fission of existing", "fission of existing peroxisomes", "of existing peroxisomes and", "existing peroxisomes and production", "peroxisomes and production of", "and production of new", "production of new peroxisomes", "of new peroxisomes from", "new peroxisomes from precursors", "peroxisomes from precursors derived", "from precursors derived from", "precursors derived from mitochondria", "derived from mitochondria and", "from mitochondria and the", "mitochondria and the er", "the er sugiura", "er sugiura et", "al. 2017 reviewed", "2017 reviewed in", "2014 hua and", "hua and kim 2016", "and kim 2016 .", "peroxisomal membrane proteins pmps", "proteins pmps are", "pmps are inserted into", "are inserted into the peroxisomal", "inserted into the peroxisomal membrane", "into the peroxisomal membrane by", "the peroxisomal membrane by the", "peroxisomal membrane by the receptor", "membrane by the receptor chaperone", "by the receptor chaperone pex19", "the receptor chaperone pex19 and", "receptor chaperone pex19 and the", "chaperone pex19 and the docking", "pex19 and the docking receptor", "and the docking receptor pex3", "docking receptor pex3 soukupova", "receptor pex3 soukupova et", "pex3 soukupova et al.", "et al. 1999 muntau", "al. 1999 muntau et", "1999 muntau et al.", "et al. 2003 fang", "al. 2003 fang et", "2003 fang et al.", "et al. 2004 fujiki", "al. 2004 fujiki et", "2004 fujiki et al.", "et al. 2006 matsuzono", "al. 2006 matsuzono and", "2006 matsuzono and fujiki", "and fujiki 2006 matsuzono", "fujiki 2006 matsuzono et", "2006 matsuzono et al.", "et al. 2006 pinto", "al. 2006 pinto et", "2006 pinto et al.", "et al. 2006 sato", "al. 2006 sato et", "2006 sato et al.", "et al. 2008 sato", "al. 2008 sato et", "2008 sato et al.", "et al. 2010 schmidt", "al. 2010 schmidt et", "2010 schmidt et al.", "et al. 2010 hattula", "al. 2010 hattula et", "2010 hattula et al.", "et al. 2014 reviewed", "al. 2014 reviewed in", "2014 reviewed in fujiki", "reviewed in fujiki et al.", "in fujiki et al. 2014", "et al. 2014 mayerhofer", "al. 2014 mayerhofer 2016", "2014 mayerhofer 2016 .", "mayerhofer 2016 . pex19 binds", "2016 . pex19 binds the", ". pex19 binds the pmp", "pex19 binds the pmp as", "binds the pmp as it", "the pmp as it is", "pmp as it is translated", "as it is translated in", "it is translated in the", "is translated in the cytosol.", "translated in the cytosol. recognition", "in the cytosol. recognition of", "the cytosol. recognition of the", "cytosol. recognition of the pmp", "recognition of the pmp by", "of the pmp by pex", "the pmp by pex 19", "pmp by pex 19 appears", "by pex 19 appears to", "pex 19 appears to depend", "19 appears to depend on", "appears to depend on positively", "to depend on positively charged", "depend on positively charged residues", "on positively charged residues in", "positively charged residues in the", "charged residues in the transmembrane", "residues in the transmembrane domain", "in the transmembrane domain of", "the transmembrane domain of the", "transmembrane domain of the pmp", "of the pmp costello", "the pmp costello et", "pmp costello et al.", "costello et al. 2017 .", "et al. 2017 . the", "al. 2017 . the pex19:pmp", "2017 . the pex19:pmp complex", ". the pex19:pmp complex then", "the pex19:pmp complex then interacts", "pex19:pmp complex then interacts with", "complex then interacts with pex3", "then interacts with pex3 located", "interacts with pex3 located in", "with pex3 located in the", "pex3 located in the peroxisomal", "located in the peroxisomal membrane.", "in the peroxisomal membrane. through", "the peroxisomal membrane. through a", "peroxisomal membrane. through a mechanism", "membrane. through a mechanism that", "through a mechanism that is", "a mechanism that is not", "mechanism that is not yet", "that is not yet clear", "not yet clear the", "yet clear the pmp", "clear the pmp is", "the pmp is inserted into", "pmp is inserted into the", "is inserted into the peroxisomal", "into the peroxisomal membrane and", "the peroxisomal membrane and pex19", "peroxisomal membrane and pex19 dissociates", "membrane and pex19 dissociates from", "and pex19 dissociates from pex3.", "pex19 dissociates from pex3. a", "dissociates from pex3. a current", "from pex3. a current model", "pex3. a current model involves", "a current model involves transfer", "current model involves transfer of", "model involves transfer of the", "involves transfer of the pmp", "transfer of the pmp from", "of the pmp from pex19", "the pmp from pex19 to", "pmp from pex19 to a", "from pex19 to a hydrophobic", "pex19 to a hydrophobic region", "to a hydrophobic region of", "a hydrophobic region of pex3", "hydrophobic region of pex3 followed", "region of pex3 followed by", "of pex3 followed by insertion", "pex3 followed by insertion of", "followed by insertion of the", "by insertion of the pmp", "insertion of the pmp into", "of the pmp into the", "the pmp into the membrane", "into the membrane chen", "the membrane chen et", "membrane chen et al.", "al. 2014 reviewed by", "2014 reviewed by giannopoulou", "reviewed by giannopoulou et al.", "by giannopoulou et al. 2016", "giannopoulou et al. 2016 .", "et al. 2016 . the", "al. 2016 . the process", "2016 . the process does", ". the process does not", "the process does not appear", "process does not appear to", "does not appear to require", "not appear to require hydrolysis", "appear to require hydrolysis of", "to require hydrolysis of atp", "require hydrolysis of atp or", "hydrolysis of atp or gtp", "atp or gtp pinto", "or gtp pinto et", "gtp pinto et al.", "pinto et al. 2006 .
unlike", "et al. 2006 .
unlike other", "al. 2006 .
unlike other pmps", ".
unlike other pmps pex3", "other pmps pex3 is", "pmps pex3 is inserted", "pex3 is inserted into the", "the peroxisomal membrane by binding", "peroxisomal membrane by binding pex19", "membrane by binding pex19 and", "by binding pex19 and then", "binding pex19 and then docking", "pex19 and then docking with", "and then docking with pex16", "docking with pex16 matsuzaki", "with pex16 matsuzaki and", "pex16 matsuzaki and fujiki", "matsuzaki and fujiki 2008 .", "and fujiki 2008 . both", "fujiki 2008 . both pex3", "2008 . both pex3 and", ". both pex3 and pex16", "both pex3 and pex16 can", "pex3 and pex16 can also", "and pex16 can also be", "pex16 can also be co", "can also be co translationally", "also be co translationally inserted", "be co translationally inserted into", "co translationally inserted into the", "translationally inserted into the endoplasmic", "inserted into the endoplasmic reticulum", "into the endoplasmic reticulum membrane", "endoplasmic reticulum membrane kim", "reticulum membrane kim et", "membrane kim et al.", "et al. 2006 yonekawa", "al. 2006 yonekawa et", "2006 yonekawa et al.", "et al. 2011 aranovich", "al. 2011 aranovich et", "2011 aranovich et al.", "et al. 2014 hua", "al. 2014 hua et", "2014 hua et al.", "et al. 2015 mayerhofer", "al. 2015 mayerhofer et", "2015 mayerhofer et al.", "mayerhofer et al. 2016 .", "et al. 2016 . this", "al. 2016 . this region", "2016 . this region of", ". this region of the", "this region of the er", "region of the er membrane", "of the er membrane then", "the er membrane then buds", "er membrane then buds to", "membrane then buds to contribute", "then buds to contribute to", "buds to contribute to new", "to contribute to new peroxisomes.", "contribute to new peroxisomes. pex3", "to new peroxisomes. pex3 is", "new peroxisomes. pex3 is also", "peroxisomes. pex3 is also observed", "pex3 is also observed to", "is also observed to insert", "also observed to insert into", "observed to insert into the", "to insert into the mitochondrial", "insert into the mitochondrial outer", "into the mitochondrial outer membrane", "mitochondrial outer membrane sugiura", "outer membrane sugiura et", "membrane sugiura et al.", "sugiura et al. 2017 .", "et al. 2017 . regions", "al. 2017 . regions of", "2017 . regions of the", ". regions of the er", "regions of the er membrane", "of the er membrane and", "the er membrane and mitochondrial", "er membrane and mitochondrial outer", "membrane and mitochondrial outer membrane", "and mitochondrial outer membrane are", "mitochondrial outer membrane are then", "outer membrane are then released", "membrane are then released to", "are then released to form", "then released to form pre", "released to form pre peroxisomal", "to form pre peroxisomal vesicles", "form pre peroxisomal vesicles which", "pre peroxisomal vesicles which fuse", "peroxisomal vesicles which fuse to", "vesicles which fuse to form", "which fuse to form new", "fuse to form new peroxisomes", "form new peroxisomes sugiura", "new peroxisomes sugiura et", "peroxisomes sugiura et al.", "et al. 2017 . peroxisomes", "al. 2017 . peroxisomes therefore", "2017 . peroxisomes therefore appear", ". peroxisomes therefore appear to", "peroxisomes therefore appear to arise", "therefore appear to arise from", "appear to arise from fission", "to arise from fission of", "arise from fission of existing", "from fission of existing peroxisomes", "fission of existing peroxisomes and", "of existing peroxisomes and production", "existing peroxisomes and production of", "peroxisomes and production of new", "and production of new peroxisomes", "production of new peroxisomes from", "of new peroxisomes from precursors", "new peroxisomes from precursors derived", "peroxisomes from precursors derived from", "from precursors derived from mitochondria", "precursors derived from mitochondria and", "derived from mitochondria and the", "from mitochondria and the er", "and the er sugiura", "the er sugiura et", "er sugiura et al.", "et al. 2017 reviewed", "al. 2017 reviewed in", "2017 reviewed in fujiki", "al. 2014 hua and", "2014 hua and kim", "hua and kim 2016 ." ] }, { "record_id": "GLY_000594_1_689", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9604323", "r hsa", "hsa 9604323", "r hsa 9604323" ] }, { "record_id": "GLY_000594_1_689", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of notch4", "notch4 signaling", "negative regulation of", "regulation of notch4", "of notch4 signaling", "negative regulation of notch4", "regulation of notch4 signaling", "negative regulation of notch4 signaling", "signaling can", "can be", "be negatively", "negatively regulated", "regulated at", "at the", "the level", "level of", "of nuclear", "nuclear translocation", "translocation of", "of the", "the notch4", "notch4 intracellular", "intracellular domain", "domain fragment", "nicd4 .", ". akt", "akt mediated", "mediated phosphorylation", "phosphorylation of", "of nicd4", "nicd4 promotes", "promotes binding", "binding of", "nicd4 with", "with 14", "14 3", "3 3", "3 zeta", "leading to", "to retention", "retention of", "nicd4 in", "in the", "the cytosol", "ramakrishnan et", "et al.", "al. 2015", "2015 .

the", ".

the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase fbxw7", "a component", "component of", "the scf", "scf ubiquitin", "ligase complex", "binds to", "to and", "and ubiquitinates", "ubiquitinates phosphorylated", "phosphorylated nicd4", "targeting it", "it for", "for proteasome", "proteasome mediated", "mediated degradation", "wu et", "al. 2001", "2001 .", ". the", "nicd4 is", "is significantly", "significantly increased", "increased in", "in fbxw7", "fbxw7 knockout", "knockout mouse", "mouse embryos", "which die", "die in", "in utero", "utero and", "and have", "have impaired", "impaired development", "development of", "the vascular", "vascular system", "tsunematsu et", "al. 2004", "2004 .

binding", ".

binding of", "notch4 to", "to eloc", "elongin c", "is involved", "involved in", "in proteasome", "degradation of", "but the", "the exact", "exact mechanism", "mechanism has", "has not", "not been", "been elucidated", "cummins et", "al. 2011", "2011 .", ". mdm2", "a tp53", "tp53 induced", "induced ubiquitin", "was reported", "reported to", "to ubiquitinate", "ubiquitinate nicd4", "nicd4 and", "and target", "target it", "for degradation", "degradation in", "in response", "response to", "to tp53", "tp53 activation", "sun et", "2011 .

notch4", ".

notch4 signaling", "signaling is", "is inhibited", "inhibited by", "by binding", "nicd4 to", "to the", "the transforming", "transforming acidic", "acidic coiled", "coiled coil", "coil protein", "protein 3", "but he", "he mechanism", "mechanism is", "is not", "not known", "bargo et", "al. 2010", "2010 .", "notch4 signaling can", "signaling can be", "can be negatively", "be negatively regulated", "negatively regulated at", "regulated at the", "at the level", "the level of", "level of nuclear", "of nuclear translocation", "nuclear translocation of", "translocation of the", "of the notch4", "the notch4 intracellular", "notch4 intracellular domain", "intracellular domain fragment", "fragment nicd4", "nicd4 . akt", ". akt mediated", "akt mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of nicd4", "of nicd4 promotes", "nicd4 promotes binding", "promotes binding of", "binding of nicd4", "of nicd4 with", "nicd4 with 14", "with 14 3", "14 3 3", "3 3 zeta", "zeta ywhaz", "leading to retention", "to retention of", "retention of nicd4", "of nicd4 in", "nicd4 in the", "in the cytosol", "cytosol ramakrishnan", "ramakrishnan et al.", "et al. 2015", "al. 2015 .

the", "2015 .

the e3", ".

the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase fbxw7", "fbxw7 a", "a component of", "component of the", "of the scf", "the scf ubiquitin", "scf ubiquitin ligase", "ubiquitin ligase complex", "complex binds", "binds to and", "to and ubiquitinates", "and ubiquitinates phosphorylated", "ubiquitinates phosphorylated nicd4", "nicd4 targeting", "targeting it for", "it for proteasome", "for proteasome mediated", "proteasome mediated degradation", "degradation wu", "wu et al.", "et al. 2001", "al. 2001 .", "2001 . the", ". the level", "level of nicd4", "of nicd4 is", "nicd4 is significantly", "is significantly increased", "significantly increased in", "increased in fbxw7", "in fbxw7 knockout", "fbxw7 knockout mouse", "knockout mouse embryos", "embryos which", "which die in", "die in utero", "in utero and", "utero and have", "and have impaired", "have impaired development", "impaired development of", "development of the", "of the vascular", "the vascular system", "system tsunematsu", "tsunematsu et al.", "et al. 2004", "al. 2004 .

binding", "2004 .

binding of", ".

binding of notch4", "of notch4 to", "notch4 to eloc", "eloc elongin", "c is", "is involved in", "involved in proteasome", "in proteasome mediated", "mediated degradation of", "degradation of notch4", "notch4 but", "but the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "has not been", "not been elucidated", "elucidated cummins", "cummins et al.", "et al. 2011", "al. 2011 .", "2011 . mdm2", "mdm2 a", "a tp53 induced", "tp53 induced ubiquitin", "induced ubiquitin ligase", "ligase was", "was reported to", "reported to ubiquitinate", "to ubiquitinate nicd4", "ubiquitinate nicd4 and", "nicd4 and target", "and target it", "target it for", "it for degradation", "for degradation in", "degradation in response", "in response to", "response to tp53", "to tp53 activation", "activation sun", "sun et al.", "al. 2011 .

notch4", "2011 .

notch4 signaling", ".

notch4 signaling is", "signaling is inhibited", "is inhibited by", "inhibited by binding", "by binding of", "of nicd4 to", "nicd4 to the", "to the transforming", "the transforming acidic", "transforming acidic coiled", "acidic coiled coil", "coiled coil protein", "coil protein 3", "3 but", "but he mechanism", "he mechanism is", "mechanism is not", "is not known", "known bargo", "bargo et al.", "et al. 2010", "al. 2010 .", "notch4 signaling can be", "signaling can be negatively", "can be negatively regulated", "be negatively regulated at", "negatively regulated at the", "regulated at the level", "at the level of", "the level of nuclear", "level of nuclear translocation", "of nuclear translocation of", "nuclear translocation of the", "translocation of the notch4", "of the notch4 intracellular", "the notch4 intracellular domain", "notch4 intracellular domain fragment", "domain fragment nicd4", "fragment nicd4 .", "nicd4 . akt mediated", ". akt mediated phosphorylation", "akt mediated phosphorylation of", "mediated phosphorylation of nicd4", "phosphorylation of nicd4 promotes", "of nicd4 promotes binding", "nicd4 promotes binding of", "promotes binding of nicd4", "binding of nicd4 with", "of nicd4 with 14", "nicd4 with 14 3", "with 14 3 3", "14 3 3 zeta", "3 zeta ywhaz", "ywhaz leading", "leading to retention of", "to retention of nicd4", "retention of nicd4 in", "of nicd4 in the", "nicd4 in the cytosol", "the cytosol ramakrishnan", "cytosol ramakrishnan et", "ramakrishnan et al. 2015", "et al. 2015 .

the", "al. 2015 .

the e3", "2015 .

the e3 ubiquitin", ".

the e3 ubiquitin ligase", "e3 ubiquitin ligase fbxw7", "ligase fbxw7 a", "fbxw7 a component", "a component of the", "component of the scf", "of the scf ubiquitin", "the scf ubiquitin ligase", "scf ubiquitin ligase complex", "ligase complex binds", "complex binds to", "binds to and ubiquitinates", "to and ubiquitinates phosphorylated", "and ubiquitinates phosphorylated nicd4", "phosphorylated nicd4 targeting", "nicd4 targeting it", "targeting it for proteasome", "it for proteasome mediated", "for proteasome mediated degradation", "mediated degradation wu", "degradation wu et", "wu et al. 2001", "et al. 2001 .", "al. 2001 . the", "2001 . the level", ". the level of", "the level of nicd4", "level of nicd4 is", "of nicd4 is significantly", "nicd4 is significantly increased", "is significantly increased in", "significantly increased in fbxw7", "increased in fbxw7 knockout", "in fbxw7 knockout mouse", "fbxw7 knockout mouse embryos", "mouse embryos which", "embryos which die", "which die in utero", "die in utero and", "in utero and have", "utero and have impaired", "and have impaired development", "have impaired development of", "impaired development of the", "development of the vascular", "of the vascular system", "vascular system tsunematsu", "system tsunematsu et", "tsunematsu et al. 2004", "et al. 2004 .

binding", "al. 2004 .

binding of", "2004 .

binding of notch4", ".

binding of notch4 to", "of notch4 to eloc", "to eloc elongin", "eloc elongin c", "elongin c is", "c is involved", "is involved in proteasome", "involved in proteasome mediated", "in proteasome mediated degradation", "proteasome mediated degradation of", "mediated degradation of notch4", "of notch4 but", "notch4 but the", "but the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been elucidated", "been elucidated cummins", "elucidated cummins et", "cummins et al. 2011", "et al. 2011 .", "al. 2011 . mdm2", ". mdm2 a", "mdm2 a tp53", "a tp53 induced ubiquitin", "tp53 induced ubiquitin ligase", "ubiquitin ligase was", "ligase was reported", "was reported to ubiquitinate", "reported to ubiquitinate nicd4", "to ubiquitinate nicd4 and", "ubiquitinate nicd4 and target", "nicd4 and target it", "and target it for", "target it for degradation", "it for degradation in", "for degradation in response", "degradation in response to", "in response to tp53", "response to tp53 activation", "tp53 activation sun", "activation sun et", "sun et al. 2011", "et al. 2011 .

notch4", "al. 2011 .

notch4 signaling", "2011 .

notch4 signaling is", ".

notch4 signaling is inhibited", "signaling is inhibited by", "is inhibited by binding", "inhibited by binding of", "by binding of nicd4", "binding of nicd4 to", "of nicd4 to the", "nicd4 to the transforming", "to the transforming acidic", "the transforming acidic coiled", "transforming acidic coiled coil", "acidic coiled coil protein", "coiled coil protein 3", "protein 3 but", "3 but he", "but he mechanism is", "he mechanism is not", "mechanism is not known", "not known bargo", "known bargo et", "bargo et al. 2010", "et al. 2010 .", "notch4 signaling can be negatively", "signaling can be negatively regulated", "can be negatively regulated at", "be negatively regulated at the", "negatively regulated at the level", "regulated at the level of", "at the level of nuclear", "the level of nuclear translocation", "level of nuclear translocation of", "of nuclear translocation of the", "nuclear translocation of the notch4", "translocation of the notch4 intracellular", "of the notch4 intracellular domain", "the notch4 intracellular domain fragment", "intracellular domain fragment nicd4", "domain fragment nicd4 .", "fragment nicd4 . akt", "nicd4 . akt mediated phosphorylation", ". akt mediated phosphorylation of", "akt mediated phosphorylation of nicd4", "mediated phosphorylation of nicd4 promotes", "phosphorylation of nicd4 promotes binding", "of nicd4 promotes binding of", "nicd4 promotes binding of nicd4", "promotes binding of nicd4 with", "binding of nicd4 with 14", "of nicd4 with 14 3", "nicd4 with 14 3 3", "with 14 3 3 zeta", "3 3 zeta ywhaz", "ywhaz leading to", "leading to retention of nicd4", "to retention of nicd4 in", "retention of nicd4 in the", "of nicd4 in the cytosol", "in the cytosol ramakrishnan", "the cytosol ramakrishnan et", "cytosol ramakrishnan et al.", "ramakrishnan et al. 2015 .

the", "et al. 2015 .

the e3", "al. 2015 .

the e3 ubiquitin", "2015 .

the e3 ubiquitin ligase", ".

the e3 ubiquitin ligase fbxw7", "ubiquitin ligase fbxw7 a", "ligase fbxw7 a component", "fbxw7 a component of", "a component of the scf", "component of the scf ubiquitin", "of the scf ubiquitin ligase", "the scf ubiquitin ligase complex", "ubiquitin ligase complex binds", "ligase complex binds to", "complex binds to and", "binds to and ubiquitinates phosphorylated", "to and ubiquitinates phosphorylated nicd4", "ubiquitinates phosphorylated nicd4 targeting", "phosphorylated nicd4 targeting it", "nicd4 targeting it for", "targeting it for proteasome mediated", "it for proteasome mediated degradation", "proteasome mediated degradation wu", "mediated degradation wu et", "degradation wu et al.", "wu et al. 2001 .", "et al. 2001 . the", "al. 2001 . the level", "2001 . the level of", ". the level of nicd4", "the level of nicd4 is", "level of nicd4 is significantly", "of nicd4 is significantly increased", "nicd4 is significantly increased in", "is significantly increased in fbxw7", "significantly increased in fbxw7 knockout", "increased in fbxw7 knockout mouse", "in fbxw7 knockout mouse embryos", "knockout mouse embryos which", "mouse embryos which die", "embryos which die in", "which die in utero and", "die in utero and have", "in utero and have impaired", "utero and have impaired development", "and have impaired development of", "have impaired development of the", "impaired development of the vascular", "development of the vascular system", "the vascular system tsunematsu", "vascular system tsunematsu et", "system tsunematsu et al.", "tsunematsu et al. 2004 .

binding", "et al. 2004 .

binding of", "al. 2004 .

binding of notch4", "2004 .

binding of notch4 to", ".

binding of notch4 to eloc", "notch4 to eloc elongin", "to eloc elongin c", "elongin c is involved", "c is involved in", "is involved in proteasome mediated", "involved in proteasome mediated degradation", "in proteasome mediated degradation of", "proteasome mediated degradation of notch4", "degradation of notch4 but", "of notch4 but the", "notch4 but the exact", "but the exact mechanism has", "the exact mechanism has not", "exact mechanism has not been", "mechanism has not been elucidated", "not been elucidated cummins", "been elucidated cummins et", "elucidated cummins et al.", "cummins et al. 2011 .", "et al. 2011 . mdm2", "2011 . mdm2 a", ". mdm2 a tp53", "mdm2 a tp53 induced", "a tp53 induced ubiquitin ligase", "induced ubiquitin ligase was", "ubiquitin ligase was reported", "ligase was reported to", "was reported to ubiquitinate nicd4", "reported to ubiquitinate nicd4 and", "to ubiquitinate nicd4 and target", "ubiquitinate nicd4 and target it", "nicd4 and target it for", "and target it for degradation", "target it for degradation in", "it for degradation in response", "for degradation in response to", "degradation in response to tp53", "in response to tp53 activation", "to tp53 activation sun", "tp53 activation sun et", "activation sun et al.", "sun et al. 2011 .

notch4", "et al. 2011 .

notch4 signaling", "al. 2011 .

notch4 signaling is", "2011 .

notch4 signaling is inhibited", ".

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misfolded ta", "2014 .
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misfolded", "et al. 2014 .
misfolded ta", "al. 2014 .
misfolded ta proteins", ".
misfolded ta proteins overexpressed", "ta proteins overexpressed ta", "proteins overexpressed ta proteins", "overexpressed ta proteins and", "ta proteins and membrane", "proteins and membrane proteins", "and membrane proteins mislocalized in", "membrane proteins mislocalized in the", "proteins mislocalized in the cytosol", "mislocalized in the cytosol bind", "in the cytosol bind sgta", "the cytosol bind sgta but", "cytosol bind sgta but are", "bind sgta but are not", "sgta but are not efficiently", "but are not efficiently transferred", "are not efficiently transferred to", "not efficiently transferred to asna1", "efficiently transferred to asna1 and", "to asna1 and instead", "and instead are", "instead are retained by", "are retained by bag6 which", "retained by bag6 which recruits", "by bag6 which recruits rnf126", "bag6 which recruits rnf126 to", "which recruits rnf126 to ubiquitinate", "recruits rnf126 to ubiquitinate them", "to ubiquitinate them targeting", "ubiquitinate them targeting them", "them targeting them for", "targeting them for degradation by", "them for degradation by the", "for degradation by the proteasome", "by the proteasome wang", "the proteasome wang et", "proteasome wang et al.", "et al. 2012 rodrigo", "al. 2012 rodrigo brenni", "2012 rodrigo brenni et", "rodrigo brenni et al. 2014", "et al. 2014 wunderly", "al. 2014 wunderly et", "2014 wunderly et al.", "2017 reviewed in lee", "reviewed in lee and ye", "in lee and ye 2013", "and ye 2013 casson", "ye 2013 casson et", "2013 casson et al.", "et al. 2016 krysztofinska", "al. 2016 krysztofinska et", "2016 krysztofinska et al.", "et al. 2016 guna", "al. 2016 guna and", "2016 guna and hegde", "guna and hegde 2018 ." ] }, { "record_id": "GLY_000594_1_691", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9609736", "r hsa", "hsa 9609736", "r hsa 9609736" ] }, { "record_id": "GLY_000594_1_691", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "assembly and", "and cell", "cell surface", "surface presentation", "presentation of", "of nmda", "nmda receptors", "assembly and cell", "and cell surface", "cell surface presentation", "surface presentation of", "presentation of nmda", "of nmda receptors", "assembly and cell surface", "and cell surface presentation", "cell surface presentation of", "surface presentation of nmda", "presentation of nmda receptors", "assembly and cell surface presentation", "and cell surface presentation of", "cell surface presentation of nmda", "surface presentation of nmda receptors", "n methyl", "methyl d", "d aspartate", "aspartate receptors", "are tetramers", "tetramers that", "that consist", "consist of", "of two", "two glun1", "subunits and", "and two", "two subunits", "subunits that", "that belong", "belong to", "to either", "either the", "the glun2", "glun2c and", "and glun2d", "or the", "the glun3", "glun3a and", "and glun3b", "glun3b .", ". the", "the glun2/glun3", "glun2/glun3 subunits", "subunits in", "in the", "the nmda", "nmda tetramer", "tetramer can", "can either", "either be", "be identical", "constituting an", "an nmda", "nmda di", "di heteromer", "di heterotetramer", "which consists", "consists of", "two subunit", "subunit types", "glun1 and", "and one", "one of", "of glun2s/glun3s", "or they", "they can", "can be", "be two", "two different", "different glun2/glun3", "glun2/glun3 proteins", "nmda tri", "tri heteromer", "tri heterotetramer", "of three", "three subunit", "two of", "monyer et", "et al.", "al. 1992", "wafford et", "al. 1993", "sheng et", "al. 1994", "dunah et", "al. 1998", "perez otano", "otano et", "al. 2001", "chatterton et", "al. 2002", "matsuda et", "yamakura et", "al. 2005", "nilsson et", "al. 2007", "hansen et", "al. 2014", "kaiser et", "al. 2018", "bhattacharya et", "bhattacharya and", "and traynelis", "traynelis 2018", "2018 .
nmda", ".
nmda tetramers", "tetramers assemble", "assemble in", "the endoplasmic", "endoplasmic reticulum", "reticulum and", "and traffic", "traffic to", "to the", "the plasma", "plasma membrane", "membrane as", "as part", "part of", "of transport", "transport vesicles", "mcilhinney et", "2001 .", ". nmda", "nmda receptor", "receptor subunits", "subunits undergo", "undergo n", "n glycosylation", "which impacts", "impacts their", "their trafficking", "trafficking from", "from the", "reticulum to", "plasma membrane.", "membrane. trafficking", "trafficking efficiency", "efficiency may", "may vary", "vary among", "among different", "different subunits", "subunits of", "of nmdars", "lichnereva et", "al. 2015", "2015 .", ". mechanistic", "mechanistic details", "such as", "as glycosyl", "glycosyl transferases", "transferases involved", "involved and", "and the", "the type", "type of", "of sugar", "sugar side", "side chains", "chains added", "are not", "not known.
as", "known.
as there", "there are", "are eight", "eight splicing", "splicing isoforms", "isoforms of", "of glun1", "four different", "different glun2", "glun2 and", "different glun3", "glun3 proteins", "many different", "different combinations", "combinations of", "of nmdar", "nmdar subunits", "subunits are", "are possible", "but only", "only a", "a handful", "handful of", "of distinct", "distinct nmdar", "nmdar receptors", "receptors have", "have been", "been experimentally", "experimentally confirmed", "confirmed and", "and functionally", "functionally studied.", "studied. the", "the composition", "composition of", "nmdars affects", "affects trafficking", "including synaptic", "ligand preference", "channel conductivity", "conductivity and", "and downstream", "downstream signal", "signal transmission.", "transmission. prevalent", "prevalent nmdars", "nmdars differ", "differ at", "at different", "different stages", "stages of", "of neuronal", "neuronal development", "in different", "different regions", "regions of", "of the", "the central", "central nervous", "nervous system", "and at", "different levels", "levels of", "neuronal activity.", "activity. for", "for review", "please refer", "refer to", "to lau", "lau and", "and zukin", "zukin 2007", "traynelis et", "al. 2010", "paoletti et", "al. 2013", "p\u00e9rez ota\u00f1o", "ota\u00f1o et", "al. 2016", "iacobucci and", "and popescu", "popescu 2017.", "n methyl d", "methyl d aspartate", "d aspartate receptors", "receptors nmdars", "nmdars are", "are tetramers that", "tetramers that consist", "that consist of", "consist of two", "of two glun1", "glun1 grin1", "grin1 subunits", "subunits and two", "and two subunits", "two subunits that", "subunits that belong", "that belong to", "belong to either", "to either the", "either the glun2", "glun2 grin2", "grin2 subfamily", "subfamily glun2a", "glun2a glun2b", "glun2b glun2c", "glun2c and glun2d", "glun2d or", "or the glun3", "glun3 grin3", "grin3 subfamily", "subfamily glun3a", "glun3a and glun3b", "and glun3b .", "glun3b . the", ". the glun2/glun3", "the glun2/glun3 subunits", "glun2/glun3 subunits in", "subunits in the", "in the nmda", "the nmda tetramer", "nmda tetramer can", "tetramer can either", "can either be", "either be identical", "identical constituting", "constituting an nmda", "an nmda di", "nmda di heteromer", "heteromer di", "which consists of", "consists of two", "of two subunit", "two subunit types", "types glun1", "glun1 and one", "and one of", "one of glun2s/glun3s", "glun2s/glun3s or", "or they can", "they can be", "can be two", "be two different", "two different glun2/glun3", "different glun2/glun3 proteins", "proteins constituting", "an nmda tri", "nmda tri heteromer", "heteromer tri", "consists of three", "of three subunit", "three subunit types", "glun1 and two", "and two of", "two of glun2s/glun3s", "glun2s/glun3s monyer", "monyer et al.", "et al. 1992", "1992 wafford", "wafford et al.", "et al. 1993", "1993 sheng", "sheng et al.", "et al. 1994", "1994 dunah", "dunah et al.", "et al. 1998", "1998 perez", "perez otano et", "otano et al.", "et al. 2001", "2001 chatterton", "chatterton et al.", "et al. 2002", "2002 matsuda", "matsuda et al.", "2002 yamakura", "yamakura et al.", "et al. 2005", "2005 nilsson", "nilsson et al.", "et al. 2007", "2007 hansen", "hansen et al.", "et al. 2014", "2014 kaiser", "kaiser et al.", "et al. 2018", "2018 bhattacharya", "bhattacharya et al.", "bhattacharya and traynelis", "and traynelis 2018", "traynelis 2018 .
nmda", "2018 .
nmda tetramers", ".
nmda tetramers assemble", "tetramers assemble in", "assemble in the", "in the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum and", "reticulum and traffic", "and traffic to", "traffic to the", "to the plasma", "the plasma membrane", "plasma membrane as", "membrane as part", "as part of", "part of transport", "of transport vesicles", "vesicles mcilhinney", "mcilhinney et al.", "al. 2001 .", "2001 . nmda", ". nmda receptor", "nmda receptor subunits", "receptor subunits undergo", "subunits undergo n", "undergo n glycosylation", "glycosylation which", "which impacts their", "impacts their trafficking", "their trafficking from", "trafficking from the", "from the endoplasmic", "endoplasmic reticulum to", "reticulum to the", "the plasma membrane.", "plasma membrane. trafficking", "membrane. trafficking efficiency", "trafficking efficiency may", "efficiency may vary", "may vary among", "vary among different", "among different subunits", "different subunits of", "subunits of nmdars", "nmdars lichnereva", "lichnereva et al.", "et al. 2015", "al. 2015 .", "2015 . mechanistic", ". mechanistic details", "details such", "such as glycosyl", "as glycosyl transferases", "glycosyl transferases involved", "transferases involved and", "involved and the", "and the type", "the type of", "type of sugar", "of sugar side", "sugar side chains", "side chains added", "added are", "are not known.
as", "not known.
as there", "known.
as there are", "there are eight", "are eight splicing", "eight splicing isoforms", "splicing isoforms of", "isoforms of glun1", "glun1 four", "four different glun2", "different glun2 and", "glun2 and two", "and two different", "two different glun3", "different glun3 proteins", "proteins many", "many different combinations", "different combinations of", "combinations of nmdar", "of nmdar subunits", "nmdar subunits are", "subunits are possible", "possible but", "but only a", "only a handful", "a handful of", "handful of distinct", "of distinct nmdar", "distinct nmdar receptors", "nmdar receptors have", "receptors have been", "have been experimentally", "been experimentally confirmed", "experimentally confirmed and", "confirmed and functionally", "and functionally studied.", "functionally studied. the", "studied. the composition", "the composition of", "composition of nmdars", "of nmdars affects", "nmdars affects trafficking", "trafficking spatial", "spatial including", "synaptic localization", "localization ligand", "preference channel", "channel conductivity and", "conductivity and downstream", "and downstream signal", "downstream signal transmission.", "signal transmission. prevalent", "transmission. prevalent nmdars", "prevalent nmdars differ", "nmdars differ at", "differ at different", "at different stages", "different stages of", "stages of neuronal", "of neuronal development", "development in", "in different regions", "different regions of", "regions of the", "of the central", "the central nervous", "central nervous system", "system and", "and at different", "at different levels", "different levels of", "levels of neuronal", "of neuronal activity.", "neuronal activity. for", "activity. for review", "review please", "please refer to", "refer to lau", "to lau and", "lau and zukin", "and zukin 2007", "2007 traynelis", "traynelis et al.", "et al. 2010", "2010 paoletti", "paoletti et al.", "et al. 2013", "2013 p\u00e9rez", "p\u00e9rez ota\u00f1o et", "ota\u00f1o et al.", "et al. 2016", "2016 iacobucci", "iacobucci and popescu", "and popescu 2017.", "n methyl d aspartate", "methyl d aspartate receptors", "aspartate receptors nmdars", "nmdars are tetramers", "are tetramers that consist", "tetramers that consist of", "that consist of two", "consist of two glun1", "two glun1 grin1", "grin1 subunits and", "subunits and two subunits", "and two subunits that", "two subunits that belong", "subunits that belong to", "that belong to either", "belong to either the", "to either the glun2", "the glun2 grin2", "glun2b glun2c and", "and glun2d or", "glun2d or the", "the glun3 grin3", "subfamily glun3a and", "glun3a and glun3b .", "and glun3b . the", "glun3b . the glun2/glun3", ". the glun2/glun3 subunits", "the glun2/glun3 subunits in", "glun2/glun3 subunits in the", "subunits in the nmda", "in the nmda tetramer", "the nmda tetramer can", "nmda tetramer can either", "tetramer can either be", "can either be identical", "be identical constituting", "identical constituting an", "constituting an nmda di", "an nmda di heteromer", "di heteromer di", "heteromer di heterotetramer", "heterotetramer which", "which consists of two", "consists of two subunit", "of two subunit types", "subunit types glun1", "types glun1 and", "glun1 and one of", "and one of glun2s/glun3s", "of glun2s/glun3s or", "glun2s/glun3s or they", "or they can be", "they can be two", "can be two different", "be two different glun2/glun3", "two different glun2/glun3 proteins", "glun2/glun3 proteins constituting", "proteins constituting an", "constituting an nmda tri", "an nmda tri heteromer", "tri heteromer tri", "heteromer tri heterotetramer", "which consists of three", "consists of three subunit", "of three subunit types", "glun1 and two of", "and two of glun2s/glun3s", "of glun2s/glun3s monyer", "glun2s/glun3s monyer et", "monyer et al. 1992", "al. 1992 wafford", "1992 wafford et", "wafford et al. 1993", "al. 1993 sheng", "1993 sheng et", "sheng et al. 1994", "al. 1994 dunah", "1994 dunah et", "dunah et al. 1998", "al. 1998 perez", "1998 perez otano", "perez otano et al.", "otano et al. 2001", "al. 2001 chatterton", "2001 chatterton et", "chatterton et al. 2002", "al. 2002 matsuda", "2002 matsuda et", "matsuda et al. 2002", "al. 2002 yamakura", "2002 yamakura et", "yamakura et al. 2005", "al. 2005 nilsson", "2005 nilsson et", "nilsson et al. 2007", "al. 2007 hansen", "2007 hansen et", "hansen et al. 2014", "al. 2014 kaiser", "2014 kaiser et", "kaiser et al. 2018", "al. 2018 bhattacharya", "2018 bhattacharya et", "bhattacharya et al. 2018", "2018 bhattacharya and", "bhattacharya and traynelis 2018", "and traynelis 2018 .
nmda", "traynelis 2018 .
nmda tetramers", "2018 .
nmda tetramers assemble", ".
nmda tetramers assemble in", "tetramers assemble in the", "assemble in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum and", "endoplasmic reticulum and traffic", "reticulum and traffic to", "and traffic to the", "traffic to the plasma", "to the plasma membrane", "the plasma membrane as", "plasma membrane as part", "membrane as part of", "as part of transport", "part of transport vesicles", "transport vesicles mcilhinney", "vesicles mcilhinney et", "mcilhinney et al. 1998", "et al. 2001 .", "al. 2001 . nmda", "2001 . nmda receptor", ". nmda receptor subunits", "nmda receptor subunits undergo", "receptor subunits undergo n", "subunits undergo n glycosylation", "n glycosylation which", "glycosylation which impacts", "which impacts their trafficking", "impacts their trafficking from", "their trafficking from the", "trafficking from the endoplasmic", "from the endoplasmic reticulum", "the endoplasmic reticulum to", "endoplasmic reticulum to the", "reticulum to the plasma", "to the plasma membrane.", "the plasma membrane. trafficking", "plasma membrane. trafficking efficiency", "membrane. trafficking efficiency may", "trafficking efficiency may vary", "efficiency may vary among", "may vary among different", "vary among different subunits", "among different subunits of", "different subunits of nmdars", "of nmdars lichnereva", "nmdars lichnereva et", "lichnereva et al. 2015", "et al. 2015 .", "al. 2015 . mechanistic", "2015 . mechanistic details", "mechanistic details such", "details such as", "such as glycosyl transferases", "as glycosyl transferases involved", "glycosyl transferases involved and", "transferases involved and the", "involved and the type", "and the type of", "the type of sugar", "type of sugar side", "of sugar side chains", "sugar side chains added", "chains added are", "added are not", "are not known.
as there", "not known.
as there are", "known.
as there are eight", "there are eight splicing", "are eight splicing isoforms", "eight splicing isoforms of", "splicing isoforms of glun1", "of glun1 four", "glun1 four different", "four different glun2 and", "different glun2 and two", "glun2 and two different", "and two different glun3", "two different glun3 proteins", "glun3 proteins many", "proteins many different", "many different combinations of", "different combinations of nmdar", "combinations of nmdar subunits", "of nmdar subunits are", "nmdar subunits are possible", "are possible but", "possible but only", "but only a handful", "only a handful of", "a handful of distinct", "handful of distinct nmdar", "of distinct nmdar receptors", "distinct nmdar receptors have", "nmdar receptors have been", "receptors have been experimentally", "have been experimentally confirmed", "been experimentally confirmed and", "experimentally confirmed and functionally", "confirmed and functionally studied.", "and functionally studied. the", "functionally studied. the composition", "studied. the composition of", "the composition of nmdars", "composition of nmdars affects", "of nmdars affects trafficking", "affects trafficking spatial", "spatial including synaptic", "including synaptic localization", "localization ligand preference", "ligand preference channel", "preference channel conductivity", "channel conductivity and downstream", "conductivity and downstream signal", "and downstream signal transmission.", "downstream signal transmission. prevalent", "signal transmission. prevalent nmdars", "transmission. prevalent nmdars differ", "prevalent nmdars differ at", "nmdars differ at different", "differ at different stages", "at different stages of", "different stages of neuronal", "stages of neuronal development", "neuronal development in", "development in different", "in different regions of", "different regions of the", "regions of the central", "of the central nervous", "the central nervous system", "nervous system and", "system and at", "and at different levels", "at different levels of", "different levels of neuronal", "levels of neuronal activity.", "of neuronal activity. for", "neuronal activity. for review", "for review please", "review please refer", "please refer to lau", "refer to lau and", "to lau and zukin", "lau and zukin 2007", "zukin 2007 traynelis", "2007 traynelis et", "traynelis et al. 2010", "al. 2010 paoletti", "2010 paoletti et", "paoletti et al. 2013", "al. 2013 p\u00e9rez", "2013 p\u00e9rez ota\u00f1o", "p\u00e9rez ota\u00f1o et al.", "ota\u00f1o et al. 2016", "al. 2016 iacobucci", "2016 iacobucci and", "iacobucci and popescu 2017.", "n methyl d aspartate receptors", "d aspartate receptors nmdars", "receptors nmdars are", "nmdars are tetramers that", "are tetramers that consist of", "tetramers that consist of two", "that consist of two glun1", "of two glun1 grin1", "glun1 grin1 subunits", "grin1 subunits and two", "subunits and two subunits that", "and two subunits that belong", "two subunits that belong to", "subunits that belong to either", "that belong to either the", "belong to either the glun2", "either the glun2 grin2", "glun2 grin2 subfamily", "grin2 subfamily glun2a", "subfamily glun2a glun2b", "glun2a glun2b glun2c", "glun2b glun2c and glun2d", "glun2c and glun2d or", "and glun2d or the", "glun2d or the glun3", "or the glun3 grin3", "glun3 grin3 subfamily", "grin3 subfamily glun3a", "subfamily glun3a and glun3b", "glun3a and glun3b . the", "and glun3b . the glun2/glun3", "glun3b . the glun2/glun3 subunits", ". the glun2/glun3 subunits in", "the glun2/glun3 subunits in the", "glun2/glun3 subunits in the nmda", "subunits in the nmda tetramer", "in the nmda tetramer can", "the nmda tetramer can either", "nmda tetramer can either be", "tetramer can either be identical", "either be identical constituting", "be identical constituting an", "identical constituting an nmda", "constituting an nmda di heteromer", "nmda di heteromer di", "di heteromer di heterotetramer", "di heterotetramer which", "heterotetramer which consists", "which consists of two subunit", "consists of two subunit types", "two subunit types glun1", "subunit types glun1 and", "types glun1 and one", "glun1 and one of glun2s/glun3s", "one of glun2s/glun3s or", "of glun2s/glun3s or they", "glun2s/glun3s or they can", "or they can be two", "they can be two different", "can be two different glun2/glun3", "be two different glun2/glun3 proteins", "different glun2/glun3 proteins constituting", "glun2/glun3 proteins constituting an", "proteins constituting an nmda", "constituting an nmda tri heteromer", "nmda tri heteromer tri", "tri heteromer tri heterotetramer", "tri heterotetramer which", "which consists of three subunit", "consists of three subunit types", "three subunit types glun1", "types glun1 and two", "glun1 and two of glun2s/glun3s", "two of glun2s/glun3s monyer", "of glun2s/glun3s monyer et", "glun2s/glun3s monyer et al.", "et al. 1992 wafford", "al. 1992 wafford et", "1992 wafford et al.", "et al. 1993 sheng", "al. 1993 sheng et", "1993 sheng et al.", "et al. 1994 dunah", "al. 1994 dunah et", "1994 dunah et al.", "et al. 1998 perez", "al. 1998 perez otano", "1998 perez otano et", "perez otano et al. 2001", "et al. 2001 chatterton", "al. 2001 chatterton et", "2001 chatterton et al.", "et al. 2002 matsuda", "al. 2002 matsuda et", "2002 matsuda et al.", "et al. 2002 yamakura", "al. 2002 yamakura et", "2002 yamakura et al.", "et al. 2005 nilsson", "al. 2005 nilsson et", "2005 nilsson et al.", "et al. 2007 hansen", "al. 2007 hansen et", "2007 hansen et al.", "et al. 2014 kaiser", "al. 2014 kaiser et", "2014 kaiser et al.", "et al. 2018 bhattacharya", "al. 2018 bhattacharya et", "2018 bhattacharya et al.", "al. 2018 bhattacharya and", "2018 bhattacharya and traynelis", "bhattacharya and traynelis 2018 .
nmda", "and traynelis 2018 .
nmda tetramers", "traynelis 2018 .
nmda tetramers assemble", "2018 .
nmda tetramers assemble in", ".
nmda tetramers assemble in the", "tetramers assemble in the endoplasmic", "assemble in the endoplasmic reticulum", "in the endoplasmic reticulum and", "the endoplasmic reticulum and traffic", "endoplasmic reticulum and traffic to", "reticulum and traffic to the", "and traffic to the plasma", "traffic to the plasma membrane", "to the plasma membrane as", "the plasma membrane as part", "plasma membrane as part of", "membrane as part of transport", "as part of transport vesicles", "of transport vesicles mcilhinney", "transport vesicles mcilhinney et", "vesicles mcilhinney et al.", "otano et al. 2001 .", "et al. 2001 . nmda", "al. 2001 . nmda receptor", "2001 . nmda receptor subunits", ". nmda receptor subunits undergo", "nmda receptor subunits undergo n", "receptor subunits undergo n glycosylation", "undergo n glycosylation which", "n glycosylation which impacts", "glycosylation which impacts their", "which impacts their trafficking from", "impacts their trafficking from the", "their trafficking from the endoplasmic", "trafficking from the endoplasmic reticulum", "from the endoplasmic reticulum to", "the endoplasmic reticulum to the", "endoplasmic reticulum to the plasma", "reticulum to the plasma membrane.", "to the plasma membrane. trafficking", "the plasma membrane. trafficking efficiency", "plasma membrane. trafficking efficiency may", "membrane. trafficking efficiency may vary", "trafficking efficiency may vary among", "efficiency may vary among different", "may vary among different subunits", "vary among different subunits of", "among different subunits of nmdars", "subunits of nmdars lichnereva", "of nmdars lichnereva et", "nmdars lichnereva et al.", "lichnereva et al. 2015 .", "et al. 2015 . mechanistic", "al. 2015 . mechanistic details", ". mechanistic details such", "mechanistic details such as", "details such as glycosyl", "such as glycosyl transferases involved", "as glycosyl transferases involved and", "glycosyl transferases involved and the", "transferases involved and the type", "involved and the type of", "and the type of sugar", "the type of sugar side", "type of sugar side chains", "of sugar side chains added", "side chains added are", "chains added are not", "added are not known.
as", "are not known.
as there are", "not known.
as there are eight", "known.
as there are eight splicing", "there are eight splicing isoforms", "are eight splicing isoforms of", "eight splicing isoforms of glun1", "isoforms of glun1 four", "of glun1 four different", "glun1 four different glun2", "four different glun2 and two", "different glun2 and two different", "glun2 and two different glun3", "and two different glun3 proteins", "different glun3 proteins many", "glun3 proteins many different", "proteins many different combinations", "many different combinations of nmdar", "different combinations of nmdar subunits", "combinations of nmdar subunits are", "of nmdar subunits are possible", "subunits are possible but", "are possible but only", "possible but only a", "but only a handful of", "only a handful of distinct", "a handful of distinct nmdar", "handful of distinct nmdar receptors", "of distinct nmdar receptors have", "distinct nmdar receptors have been", "nmdar receptors have been experimentally", "receptors have been experimentally confirmed", "have been experimentally confirmed and", "been experimentally confirmed and functionally", "experimentally confirmed and functionally studied.", "confirmed and functionally studied. the", "and functionally studied. the composition", "functionally studied. the composition of", "studied. the composition of nmdars", "the composition of nmdars affects", "composition of nmdars affects trafficking", "nmdars affects trafficking spatial", "trafficking spatial including", "synaptic localization ligand", "ligand preference channel conductivity", "preference channel conductivity and", "channel conductivity and downstream signal", "conductivity and downstream signal transmission.", "and downstream signal transmission. prevalent", "downstream signal transmission. prevalent nmdars", "signal transmission. prevalent nmdars differ", "transmission. prevalent nmdars differ at", "prevalent nmdars differ at different", "nmdars differ at different stages", "differ at different stages of", "at different stages of neuronal", "different stages of neuronal development", "of neuronal development in", "neuronal development in different", "development in different regions", "in different regions of the", "different regions of the central", "regions of the central nervous", "of the central nervous system", "central nervous system and", "nervous system and at", "system and at different", "and at different levels of", "at different levels of neuronal", "different levels of neuronal activity.", "levels of neuronal activity. for", "of neuronal activity. for review", "activity. for review please", "for review please refer", "review please refer to", "please refer to lau and", "refer to lau and zukin", "to lau and zukin 2007", "and zukin 2007 traynelis", "zukin 2007 traynelis et", "2007 traynelis et al.", "et al. 2010 paoletti", "al. 2010 paoletti et", "2010 paoletti et al.", "et al. 2013 p\u00e9rez", "al. 2013 p\u00e9rez ota\u00f1o", "2013 p\u00e9rez ota\u00f1o et", "p\u00e9rez ota\u00f1o et al. 2016", "et al. 2016 iacobucci", "al. 2016 iacobucci and", "2016 iacobucci and popescu" ] }, { "record_id": "GLY_000594_1_692", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9614399", "r hsa", "hsa 9614399", "r hsa 9614399" ] }, { "record_id": "GLY_000594_1_692", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of localization", "localization of", "of foxo", "foxo transcription", "transcription factors", "regulation of localization", "of localization of", "localization of foxo", "of foxo transcription", "foxo transcription factors", "regulation of localization of", "of localization of foxo", "localization of foxo transcription", "of foxo transcription factors", "regulation of localization of foxo", "of localization of foxo transcription", "localization of foxo transcription factors", "factors foxo1", "foxo3 and", "and foxo4", "foxo4 is", "is regulated", "regulated by", "by akt", "akt mediated", "mediated phosphorylation.", "phosphorylation. in", "in the", "the absence", "absence of", "of pi3k/akt", "pi3k/akt signaling", "foxo4 localize", "localize to", "to the", "the nucleus.", "nucleus. akt", "mediated phosphorylation", "phosphorylation induces", "induces a", "a conformational", "conformational change", "change that", "that exposes", "exposes a", "a nuclear", "nuclear export", "export signal", "and promotes", "promotes translocation", "translocation of", "of foxo1", "foxo4 to", "the cytosol", "rena et", "et al.", "al. 1999", "brunet et", "kops et", "1999 .", ". akt", "akt phosphorylated", "phosphorylated foxo1", "foxo4 bind", "bind to", "to 14", "14 3", "3 3", "3 proteins", "which contributes", "contributes to", "to their", "their retention", "retention in", "al. 2001", "arimoto ishida", "ishida et", "al. 2004", "obsilova et", "al. 2005", "boura et", "al. 2007", "silhan et", "al. 2009", "2009 .", ". foxo6", "foxo6 lacks", "lacks the", "the nes", "nes sequence", "sequence and", "and is", "is exclusively", "exclusively nuclear", "but phosphorylation", "phosphorylation in", "in response", "response to", "to pi3k/akt", "signaling affects", "affects the", "the transcriptional", "transcriptional activity", "activity of", "of foxo6", "jacobs et", "al. 2003", "van der", "der heide", "heide et", "2005 .", "transcription factors foxo1", "foxo1 foxo3", "foxo3 and foxo4", "and foxo4 is", "foxo4 is regulated", "is regulated by", "regulated by akt", "by akt mediated", "akt mediated phosphorylation.", "mediated phosphorylation. in", "phosphorylation. in the", "in the absence", "the absence of", "absence of pi3k/akt", "of pi3k/akt signaling", "signaling foxo1", "and foxo4 localize", "foxo4 localize to", "localize to the", "to the nucleus.", "the nucleus. akt", "nucleus. akt mediated", "akt mediated phosphorylation", "mediated phosphorylation induces", "phosphorylation induces a", "induces a conformational", "a conformational change", "conformational change that", "change that exposes", "that exposes a", "exposes a nuclear", "a nuclear export", "nuclear export signal", "signal nes", "nes and", "and promotes translocation", "promotes translocation of", "translocation of foxo1", "and foxo4 to", "foxo4 to the", "to the cytosol", "cytosol rena", "rena et al.", "et al. 1999", "1999 brunet", "brunet et al.", "1999 kops", "kops et al.", "al. 1999 .", "1999 . akt", ". akt phosphorylated", "akt phosphorylated foxo1", "and foxo4 bind", "foxo4 bind to", "bind to 14", "to 14 3", "14 3 3", "3 3 proteins", "proteins which", "which contributes to", "contributes to their", "to their retention", "their retention in", "retention in the", "in the cytosol", "et al. 2001", "2001 brunet", "1999 arimoto", "arimoto ishida et", "ishida et al.", "et al. 2004", "2004 obsilova", "obsilova et al.", "et al. 2005", "2005 boura", "boura et al.", "et al. 2007", "2007 silhan", "silhan et al.", "et al. 2009", "al. 2009 .", "2009 . foxo6", ". foxo6 lacks", "foxo6 lacks the", "lacks the nes", "the nes sequence", "nes sequence and", "sequence and is", "and is exclusively", "is exclusively nuclear", "nuclear but", "but phosphorylation in", "phosphorylation in response", "in response to", "response to pi3k/akt", "to pi3k/akt signaling", "pi3k/akt signaling affects", "signaling affects the", "affects the transcriptional", "the transcriptional activity", "transcriptional activity of", "activity of foxo6", "foxo6 jacobs", "jacobs et al.", "et al. 2003", "2003 van", "van der heide", "der heide et", "heide et al.", "al. 2005 .", "foxo transcription factors foxo1", "factors foxo1 foxo3", "foxo1 foxo3 and", "foxo3 and foxo4 is", "and foxo4 is regulated", "foxo4 is regulated by", "is regulated by akt", "regulated by akt mediated", "by akt mediated phosphorylation.", "akt mediated phosphorylation. in", "mediated phosphorylation. in the", "phosphorylation. in the absence", "in the absence of", "the absence of pi3k/akt", "absence of pi3k/akt signaling", "pi3k/akt signaling foxo1", "foxo3 and foxo4 localize", "and foxo4 localize to", "foxo4 localize to the", "localize to the nucleus.", "to the nucleus. akt", "the nucleus. akt mediated", "nucleus. akt mediated phosphorylation", "akt mediated phosphorylation induces", "mediated phosphorylation induces a", "phosphorylation induces a conformational", "induces a conformational change", "a conformational change that", "conformational change that exposes", "change that exposes a", "that exposes a nuclear", "exposes a nuclear export", "a nuclear export signal", "export signal nes", "nes and promotes", "and promotes translocation of", "promotes translocation of foxo1", "of foxo1 foxo3", "foxo3 and foxo4 to", "and foxo4 to the", "foxo4 to the cytosol", "the cytosol rena", "cytosol rena et", "rena et al. 1999", "al. 1999 brunet", "1999 brunet et", "brunet et al. 1999", "al. 1999 kops", "1999 kops et", "kops et al. 1999", "et al. 1999 .", "al. 1999 . akt", "1999 . akt phosphorylated", ". akt phosphorylated foxo1", "phosphorylated foxo1 foxo3", "foxo3 and foxo4 bind", "and foxo4 bind to", "foxo4 bind to 14", "bind to 14 3", "to 14 3 3", "14 3 3 proteins", "3 proteins which", "proteins which contributes", "which contributes to their", "contributes to their retention", "to their retention in", "their retention in the", "retention in the cytosol", "rena et al. 2001", "al. 2001 brunet", "2001 brunet et", "al. 1999 arimoto", "1999 arimoto ishida", "arimoto ishida et al.", "ishida et al. 2004", "al. 2004 obsilova", "2004 obsilova et", "obsilova et al. 2005", "al. 2005 boura", "2005 boura et", "boura et al. 2007", "al. 2007 silhan", "2007 silhan et", "silhan et al. 2009", "et al. 2009 .", "al. 2009 . foxo6", "2009 . foxo6 lacks", ". foxo6 lacks the", "foxo6 lacks the nes", "lacks the nes sequence", "the nes sequence and", "nes sequence and is", "sequence and is exclusively", "and is exclusively nuclear", "exclusively nuclear but", "nuclear but phosphorylation", "but phosphorylation in response", "phosphorylation in response to", "in response to pi3k/akt", "response to pi3k/akt signaling", "to pi3k/akt signaling affects", "pi3k/akt signaling affects the", "signaling affects the transcriptional", "affects the transcriptional activity", "the transcriptional activity of", "transcriptional activity of foxo6", "of foxo6 jacobs", "foxo6 jacobs et", "jacobs et al. 2003", "al. 2003 van", "2003 van der", "van der heide et", "der heide et al.", "heide et al. 2005", "et al. 2005 .", "of foxo transcription factors foxo1", "transcription factors foxo1 foxo3", "factors foxo1 foxo3 and", "foxo1 foxo3 and foxo4", "foxo3 and foxo4 is regulated", "and foxo4 is regulated by", "foxo4 is regulated by akt", "is regulated by akt mediated", "regulated by akt mediated phosphorylation.", "by akt mediated phosphorylation. in", "akt mediated phosphorylation. in the", "mediated phosphorylation. in the absence", "phosphorylation. in the absence of", "in the absence of pi3k/akt", "the absence of pi3k/akt signaling", "of pi3k/akt signaling foxo1", "signaling foxo1 foxo3", "foxo3 and foxo4 localize to", "and foxo4 localize to the", "foxo4 localize to the nucleus.", "localize to the nucleus. akt", "to the nucleus. akt mediated", "the nucleus. akt mediated phosphorylation", "nucleus. akt mediated phosphorylation induces", "akt mediated phosphorylation induces a", "mediated phosphorylation induces a conformational", "phosphorylation induces a conformational change", "induces a conformational change that", "a conformational change that exposes", "conformational change that exposes a", "change that exposes a nuclear", "that exposes a nuclear export", "exposes a nuclear export signal", "nuclear export signal nes", "signal nes and", "nes and promotes translocation", "and promotes translocation of foxo1", "translocation of foxo1 foxo3", "of foxo1 foxo3 and", "foxo3 and foxo4 to the", "and foxo4 to the cytosol", "to the cytosol rena", "the cytosol rena et", "cytosol rena et al.", "et al. 1999 brunet", "al. 1999 brunet et", "1999 brunet et al.", "et al. 1999 kops", "al. 1999 kops et", "1999 kops et al.", "kops et al. 1999 .", "et al. 1999 . akt", "al. 1999 . akt phosphorylated", "1999 . akt phosphorylated foxo1", "akt phosphorylated foxo1 foxo3", "phosphorylated foxo1 foxo3 and", "foxo3 and foxo4 bind to", "and foxo4 bind to 14", "foxo4 bind to 14 3", "bind to 14 3 3", "to 14 3 3 proteins", "3 3 proteins which", "3 proteins which contributes", "proteins which contributes to", "which contributes to their retention", "contributes to their retention in", "to their retention in the", "their retention in the cytosol", "in the cytosol rena", "et al. 2001 brunet", "al. 2001 brunet et", "2001 brunet et al.", "et al. 1999 arimoto", "al. 1999 arimoto ishida", "1999 arimoto ishida et", "arimoto ishida et al. 2004", "et al. 2004 obsilova", "al. 2004 obsilova et", "2004 obsilova et al.", "et al. 2005 boura", "al. 2005 boura et", "2005 boura et al.", "et al. 2007 silhan", "al. 2007 silhan et", "2007 silhan et al.", "silhan et al. 2009 .", "et al. 2009 . foxo6", "al. 2009 . foxo6 lacks", "2009 . foxo6 lacks the", ". foxo6 lacks the nes", "foxo6 lacks the nes sequence", "lacks the nes sequence and", "the nes sequence and is", "nes sequence and is exclusively", "sequence and is exclusively nuclear", "is exclusively nuclear but", "exclusively nuclear but phosphorylation", "nuclear but phosphorylation in", "but phosphorylation in response to", "phosphorylation in response to pi3k/akt", "in response to pi3k/akt signaling", "response to pi3k/akt signaling affects", "to pi3k/akt signaling affects the", "pi3k/akt signaling affects the transcriptional", "signaling affects the transcriptional activity", "affects the transcriptional activity of", "the transcriptional activity of foxo6", "activity of foxo6 jacobs", "of foxo6 jacobs et", "foxo6 jacobs et al.", "et al. 2003 van", "al. 2003 van der", "2003 van der heide", "van der heide et al.", "der heide et al. 2005", "heide et al. 2005 ." ] }, { "record_id": "GLY_000594_1_693", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9615017", "r hsa", "hsa 9615017", "r hsa 9615017" ] }, { "record_id": "GLY_000594_1_693", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "foxo mediated", "mediated transcription", "transcription of", "of oxidative", "oxidative stress", "metabolic and", "and neuronal", "neuronal genes", "foxo mediated transcription", "mediated transcription of", "transcription of oxidative", "of oxidative stress", "stress metabolic", "metabolic and neuronal", "and neuronal genes", "foxo mediated transcription of", "mediated transcription of oxidative", "transcription of oxidative stress", "oxidative stress metabolic", "stress metabolic and", "metabolic and neuronal genes", "foxo mediated transcription of oxidative", "mediated transcription of oxidative stress", "of oxidative stress metabolic", "oxidative stress metabolic and", "stress metabolic and neuronal", "the least", "least studied", "studied member", "member of", "of the", "the foxo", "foxo family", "directly stimulates", "stimulates transcription", "of plxna4", "plxna4 gene", "encoding a", "a co", "co factor", "factor for", "for the", "the semaphorin", "semaphorin sema3a", "sema3a receptor.", "receptor. foxo6", "foxo6 mediated", "mediated regulation", "regulation of", "plxna4 expression", "expression plays", "plays an", "an important", "important role", "role in", "in radial", "radial glia", "glia migration", "migration during", "during cortical", "cortical development", "paap et", "et al.", "al. 2016", "2016 .
foxo", ".
foxo mediated", "mediated up", "up regulation", "of genes", "genes involved", "involved in", "in reduction", "reduction of", "the oxidative", "stress burden", "burden is", "is not", "not specific", "specific to", "to neurons", "but plays", "in neuronal", "neuronal survival", "survival and", "and neurodegenerative", "neurodegenerative diseases.", "diseases. foxo3", "foxo3 and", "and foxo4", "and possibly", "possibly foxo1", "directly stimulate", "stimulate transcription", "the sod2", "sod2 gene", "encoding mitochondrial", "mitochondrial manganese", "manganese dependent", "dependent superoxide", "superoxide dismutase", "which converts", "converts superoxide", "superoxide to", "to the", "the less", "less harmful", "harmful hydrogen", "hydrogen peroxide", "peroxide and", "and oxygen", "kops et", "al. 2002", "hori et", "al. 2013", "araujo et", "al. 2011", "guan et", "2016 .", ". foxo4", "foxo4 stimulates", "stimulates sod2", "gene transcription", "transcription in", "in collaboration", "collaboration with", "with atxn3", "a protein", "protein involved", "in spinocerebellar", "spinocerebellar ataxia", "ataxia type", "type 3", "2011 .", ". foxo3", "and foxo6", "the cat", "cat gene", "encoding catalase", "an enzyme", "enzyme that", "that converts", "converts hydrogen", "peroxide to", "to water", "water and", "thus protecting", "protecting cells", "cells from", "from the", "awad et", "al. 2014", "kim et", "rangarajan et", "al. 2015", "song et", "liao et", "guo et", ".
foxo transcription", "transcription factors", "factors regulate", "regulate transcription", "of several", "several genes", "genes whose", "whose protein", "protein products", "products are", "are secreted", "secreted from", "from hypothalamic", "hypothalamic neurons", "neurons to", "to control", "control appetite", "appetite and", "and food", "food intake:", "intake: npy", "npy gene", "agrp gene", "gene and", "and pomc", "pomc gene.", "gene. at", "at low", "low insulin", "insulin levels", "characteristic of", "of starvation", "foxo transcription", "factors bind", "bind to", "to insulin", "insulin responsive", "responsive elements", "in the", "the regulatory", "regulatory regions", "regions of", "of npy", "agrp and", "gene. foxo1", "foxo1 directly", "the npy", "encoding neuropeptide", "neuropeptide y", "al. 2006", "hong et", "al. 2012", "and the", "the agrp", "encoding agouti", "agouti related", "related protein", "kitamura et", "which both", "both stimulate", "stimulate food", "food intake.", "intake. at", "at the", "the same", "same time", "directly represses", "represses transcription", "the pomc", "pomc gene", "encoding melanocyte", "melanocyte stimulating", "stimulating hormone", "hormone alpha", "which suppresses", "suppresses food", "food intake", "2006 .", ". when", "upon food", "blood insulin", "levels rise", "insulin mediated", "mediated activation", "activation of", "of pi3k/akt", "pi3k/akt signaling", "signaling inhibits", "inhibits foxo", "foxo transcriptional", "transcriptional activity.
in", "activity.
in liver", "liver cells", "in gluconeogenesis:", "gluconeogenesis: g6pc", "g6pc gene", "encoding glucose", "glucose 6", "6 phosphatase", "phosphatase and", "and pck1", "pck1 gene", "encoding phosphoenolpyruvate", "phosphoenolpyruvate carboxykinase.", "carboxykinase. actions", "actions of", "of g6pc", "g6pc and", "pck1 enable", "enable steady", "steady glucose", "glucose blood", "blood levels", "levels during", "during fasting.", "fasting. foxo1", "foxo4 directly", "stimulate pck1", "hall et", "al. 2000", "yang et", "puigserver et", "al. 2003", "while all", "all four", "four foxos", "foxo4 and", "foxo6 directly", "stimulate g6pc", "onuma et", ". foxo", "mediated induction", "induction of", "pck1 genes", "genes is", "is negatively", "negatively regulated", "regulated by", "by insulin", "insulin induced", "induced pi3k/akt", "pi3k/akt signaling.
foxo1", "the igfbp1", "igfbp1 gene", "encoding insulin", "insulin growth", "growth factor", "factor binding", "binding protein", "protein 2", "tang et", "al. 1999", "which increases", "increases sensitivity", "sensitivity of", "of cells", "cells to", "to insulin.
foxo1", "insulin.
foxo1 and", "and foxo3", "foxo3 directly", "the abca6", "atp binding", "binding cassette", "cassette sub", "sub family", "family a", "a member", "member 6", "a putative", "putative transporter", "transporter protein", "protein that", "that is", "is thought", "thought to", "to be", "be involved", "in lipid", "lipid homeostasis", "gai et", "2013 .", ". the", "the gck", "gene is", "is another", "another gene", "gene involved", "homeostasis that", "is regulated", "by foxos.", "foxos. foxo1", "acting with", "with the", "the sin3a:hdac", "sin3a:hdac complex", "represses the", "gck gene", "thus repressing", "repressing lipogenesis", "lipogenesis in", "the absence", "absence of", "of insulin", "langlet et", "al. 2017", "2017 .", "the srebf1", "which encodes", "encodes a", "a transcriptional", "transcriptional activator", "activator required", "required for", "for lipid", "is directly", "directly transcriptionally", "transcriptionally repressed", "repressed by", "by foxo1", "deng et", "2012 .", ". transcription", "the retn", "retn gene", "encoding resistin", "an adipocyte", "adipocyte specific", "specific hormone", "hormone that", "that suppresses", "suppresses insulin", "mediated uptake", "uptake of", "of glucose", "glucose by", "by adipose", "adipose cells", "directly stimulated", "stimulated by", "liu et", "2014 .
transcription", ".
transcription of", "of two", "two genes", "genes encoding", "encoding e3", "e3 ubiquitin", "ubiquitin ligases", "ligases fbxo32", "atrogin 1", "and trim63", "in degradation", "degradation of", "of muscle", "muscle proteins", "proteins and", "and muscle", "muscle wasting", "wasting during", "during starvation", "is positively", "positively regulated", "by foxo", "sandri et", "al. 2004", "waddell et", "al. 2008", "raffaello et", "al. 2010", "senf et", "bollinger et", "wang et", "foxo6 the", "the least studied", "least studied member", "studied member of", "member of the", "of the foxo", "the foxo family", "family directly", "directly stimulates transcription", "stimulates transcription of", "transcription of plxna4", "of plxna4 gene", "gene encoding", "encoding a co", "a co factor", "co factor for", "factor for the", "for the semaphorin", "the semaphorin sema3a", "semaphorin sema3a receptor.", "sema3a receptor. foxo6", "receptor. foxo6 mediated", "foxo6 mediated regulation", "mediated regulation of", "regulation of plxna4", "of plxna4 expression", "plxna4 expression plays", "expression plays an", "plays an important", "an important role", "important role in", "role in radial", "in radial glia", "radial glia migration", "glia migration during", "migration during cortical", "during cortical development", "development paap", "paap et al.", "et al. 2016", "al. 2016 .
foxo", "2016 .
foxo mediated", ".
foxo mediated up", "mediated up regulation", "up regulation of", "regulation of genes", "of genes involved", "genes involved in", "involved in reduction", "in reduction of", "reduction of the", "of the oxidative", "the oxidative stress", "oxidative stress burden", "stress burden is", "burden is not", "is not specific", "not specific to", "specific to neurons", "neurons but", "but plays an", "role in neuronal", "in neuronal survival", "neuronal survival and", "survival and neurodegenerative", "and neurodegenerative diseases.", "neurodegenerative diseases. foxo3", "diseases. foxo3 and", "foxo3 and foxo4", "and possibly foxo1", "directly stimulate transcription", "stimulate transcription of", "transcription of the", "of the sod2", "the sod2 gene", "encoding mitochondrial manganese", "mitochondrial manganese dependent", "manganese dependent superoxide", "dependent superoxide dismutase", "dismutase which", "which converts superoxide", "converts superoxide to", "superoxide to the", "to the less", "the less harmful", "less harmful hydrogen", "harmful hydrogen peroxide", "hydrogen peroxide and", "peroxide and oxygen", "oxygen kops", "kops et al.", "et al. 2002", "2002 hori", "hori et al.", "et al. 2013", "2013 araujo", "araujo et al.", "et al. 2011", "2011 guan", "guan et al.", "al. 2016 .", "2016 . foxo4", ". foxo4 stimulates", "foxo4 stimulates sod2", "stimulates sod2 gene", "sod2 gene transcription", "gene transcription in", "transcription in collaboration", "in collaboration with", "collaboration with atxn3", "atxn3 a", "a protein involved", "protein involved in", "involved in spinocerebellar", "in spinocerebellar ataxia", "spinocerebellar ataxia type", "ataxia type 3", "3 sca3", "al. 2011 .", "2011 . foxo3", ". foxo3 and", "foxo3 and foxo6", "foxo6 and", "of the cat", "the cat gene", "catalase an", "an enzyme that", "enzyme that converts", "that converts hydrogen", "converts hydrogen peroxide", "hydrogen peroxide to", "peroxide to water", "to water and", "water and oxygen", "oxygen thus", "thus protecting cells", "protecting cells from", "cells from the", "from the oxidative", "stress awad", "awad et al.", "et al. 2014", "2014 kim", "kim et al.", "2014 rangarajan", "rangarajan et al.", "et al. 2015", "2015 song", "song et al.", "2016 liao", "liao et al.", "2016 guo", "guo et al.", "2016 .
foxo transcription", ".
foxo transcription factors", "transcription factors regulate", "factors regulate transcription", "regulate transcription of", "transcription of several", "of several genes", "several genes whose", "genes whose protein", "whose protein products", "protein products are", "products are secreted", "are secreted from", "secreted from hypothalamic", "from hypothalamic neurons", "hypothalamic neurons to", "neurons to control", "to control appetite", "control appetite and", "appetite and food", "and food intake:", "food intake: npy", "intake: npy gene", "gene agrp", "agrp gene and", "gene and pomc", "and pomc gene.", "pomc gene. at", "gene. at low", "at low insulin", "low insulin levels", "levels characteristic", "characteristic of starvation", "starvation foxo", "foxo transcription factors", "transcription factors bind", "factors bind to", "bind to insulin", "to insulin responsive", "insulin responsive elements", "elements ires", "ires in", "in the regulatory", "the regulatory regions", "regulatory regions of", "regions of npy", "npy agrp", "agrp and pomc", "pomc gene. foxo1", "gene. foxo1 directly", "foxo1 directly stimulates", "of the npy", "the npy gene", "encoding neuropeptide y", "y kim", "et al. 2006", "2006 hong", "hong et al.", "et al. 2012", "and the agrp", "the agrp gene", "encoding agouti related", "agouti related protein", "protein kitamura", "kitamura et al.", "2006 kim", "which both stimulate", "both stimulate food", "stimulate food intake.", "food intake. at", "intake. at the", "at the same", "the same time", "time foxo1", "foxo1 directly represses", "directly represses transcription", "represses transcription of", "of the pomc", "the pomc gene", "encoding melanocyte stimulating", "melanocyte stimulating hormone", "stimulating hormone alpha", "which suppresses food", "suppresses food intake", "intake kitamura", "al. 2006 .", "2006 . when", "when upon", "upon food intake", "intake blood", "blood insulin levels", "insulin levels rise", "rise insulin", "insulin mediated activation", "mediated activation of", "activation of pi3k/akt", "of pi3k/akt signaling", "pi3k/akt signaling inhibits", "signaling inhibits foxo", "inhibits foxo transcriptional", "foxo transcriptional activity.
in", "transcriptional activity.
in liver", "activity.
in liver cells", "cells foxo", "transcription of genes", "involved in gluconeogenesis:", "in gluconeogenesis: g6pc", "gluconeogenesis: g6pc gene", "encoding glucose 6", "glucose 6 phosphatase", "6 phosphatase and", "phosphatase and pck1", "and pck1 gene", "encoding phosphoenolpyruvate carboxykinase.", "phosphoenolpyruvate carboxykinase. actions", "carboxykinase. actions of", "actions of g6pc", "of g6pc and", "g6pc and pck1", "and pck1 enable", "pck1 enable steady", "enable steady glucose", "steady glucose blood", "glucose blood levels", "blood levels during", "levels during fasting.", "during fasting. foxo1", "foxo1 foxo3", "and foxo4 directly", "foxo4 directly stimulate", "directly stimulate pck1", "stimulate pck1 gene", "pck1 gene transcription", "transcription hall", "hall et al.", "et al. 2000", "2000 yang", "yang et al.", "2002 puigserver", "puigserver et al.", "et al. 2003", "while all four", "all four foxos", "foxos foxo1", "foxo3 foxo4", "foxo4 and foxo6", "and foxo6 directly", "foxo6 directly stimulate", "directly stimulate g6pc", "stimulate g6pc gene", "g6pc gene transcription", "transcription yang", "2003 onuma", "onuma et al.", "2011 . foxo", ". foxo mediated", "foxo mediated induction", "mediated induction of", "induction of g6pc", "and pck1 genes", "pck1 genes is", "genes is negatively", "is negatively regulated", "negatively regulated by", "regulated by insulin", "by insulin induced", "insulin induced pi3k/akt", "induced pi3k/akt signaling.
foxo1", "signaling.
foxo1 foxo3", "of the igfbp1", "the igfbp1 gene", "encoding insulin growth", "insulin growth factor", "growth factor binding", "factor binding protein", "binding protein 2", "2 tang", "tang et al.", "et al. 1999", "1999 kops", "1999 hall", "which increases sensitivity", "increases sensitivity of", "sensitivity of cells", "of cells to", "cells to insulin.
foxo1", "to insulin.
foxo1 and", "insulin.
foxo1 and foxo3", "and foxo3 directly", "foxo3 directly stimulate", "of the abca6", "abca6 atp", "atp binding cassette", "binding cassette sub", "cassette sub family", "sub family a", "family a member", "a member 6", "6 gene", "encoding a putative", "a putative transporter", "putative transporter protein", "transporter protein that", "protein that is", "that is thought", "is thought to", "thought to be", "to be involved", "be involved in", "involved in lipid", "in lipid homeostasis", "homeostasis gai", "gai et al.", "al. 2013 .", "2013 . the", ". the gck", "gck glucokinase", "glucokinase gene", "gene is another", "is another gene", "another gene involved", "gene involved in", "lipid homeostasis that", "homeostasis that is", "that is regulated", "is regulated by", "regulated by foxos.", "by foxos. foxo1", "foxo1 acting", "acting with the", "with the sin3a:hdac", "the sin3a:hdac complex", "complex directly", "directly represses the", "represses the gck", "the gck gene", "gck gene transcription", "transcription thus", "thus repressing lipogenesis", "repressing lipogenesis in", "lipogenesis in the", "in the absence", "the absence of", "absence of insulin", "insulin langlet", "langlet et al.", "et al. 2017", "al. 2017 .", "2017 . the", ". the srebf1", "srebf1 srebp1", "srebp1 gene", "gene which", "which encodes a", "encodes a transcriptional", "a transcriptional activator", "transcriptional activator required", "activator required for", "required for lipid", "for lipid homeostasis", "homeostasis is", "is directly transcriptionally", "directly transcriptionally repressed", "transcriptionally repressed by", "repressed by foxo1", "foxo1 deng", "deng et al.", "al. 2012 .", "2012 . transcription", ". transcription of", "of the retn", "the retn gene", "resistin an", "an adipocyte specific", "adipocyte specific hormone", "specific hormone that", "hormone that suppresses", "that suppresses insulin", "suppresses insulin mediated", "insulin mediated uptake", "mediated uptake of", "uptake of glucose", "of glucose by", "glucose by adipose", "by adipose cells", "cells is", "is directly stimulated", "directly stimulated by", "stimulated by foxo1", "foxo1 liu", "liu et al.", "al. 2014 .
transcription", "2014 .
transcription of", ".
transcription of two", "of two genes", "two genes encoding", "genes encoding e3", "encoding e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases fbxo32", "fbxo32 atrogin", "1 and", "trim63 murf1", "involved in degradation", "in degradation of", "degradation of muscle", "of muscle proteins", "muscle proteins and", "proteins and muscle", "and muscle wasting", "muscle wasting during", "wasting during starvation", "starvation is", "is positively regulated", "positively regulated by", "regulated by foxo", "by foxo transcription", "factors sandri", "sandri et al.", "et al. 2004", "2004 waddell", "waddell et al.", "et al. 2008", "2008 raffaello", "raffaello et al.", "et al. 2010", "2010 senf", "senf et al.", "2011 bollinger", "bollinger et al.", "2014 wang", "wang et al.", "foxo6 the least", "the least studied member", "least studied member of", "studied member of the", "member of the foxo", "of the foxo family", "foxo family directly", "family directly stimulates", "directly stimulates transcription of", "stimulates transcription of plxna4", "transcription of plxna4 gene", "plxna4 gene encoding", "gene encoding a", "encoding a co factor", "a co factor for", "co factor for the", "factor for the semaphorin", "for the semaphorin sema3a", "the semaphorin sema3a receptor.", "semaphorin sema3a receptor. foxo6", "sema3a receptor. foxo6 mediated", "receptor. foxo6 mediated regulation", "foxo6 mediated regulation of", "mediated regulation of plxna4", "regulation of plxna4 expression", "of plxna4 expression plays", "plxna4 expression plays an", "expression plays an important", "plays an important role", "an important role in", "important role in radial", "role in radial glia", "in radial glia migration", "radial glia migration during", "glia migration during cortical", "migration during cortical development", "cortical development paap", "development paap et", "paap et al. 2016", "et al. 2016 .
foxo", "al. 2016 .
foxo mediated", "2016 .
foxo mediated up", ".
foxo mediated up regulation", "mediated up regulation of", "up regulation of genes", "regulation of genes involved", "of genes involved in", "genes involved in reduction", "involved in reduction of", "in reduction of the", "reduction of the oxidative", "of the oxidative stress", "the oxidative stress burden", "oxidative stress burden is", "stress burden is not", "burden is not specific", "is not specific to", "not specific to neurons", "to neurons but", "neurons but plays", "but plays an important", "important role in neuronal", "role in neuronal survival", "in neuronal survival and", "neuronal survival and neurodegenerative", "survival and neurodegenerative diseases.", "and neurodegenerative diseases. foxo3", "neurodegenerative diseases. foxo3 and", "diseases. foxo3 and foxo4", "and foxo4 and", "foxo4 and possibly", "possibly foxo1 directly", "foxo1 directly stimulate", "directly stimulate transcription of", "stimulate transcription of the", "transcription of the sod2", "of the sod2 gene", "sod2 gene encoding", "gene encoding mitochondrial", "encoding mitochondrial manganese dependent", "mitochondrial manganese dependent superoxide", "manganese dependent superoxide dismutase", "superoxide dismutase which", "dismutase which converts", "which converts superoxide to", "converts superoxide to the", "superoxide to the less", "to the less harmful", "the less harmful hydrogen", "less harmful hydrogen peroxide", "harmful hydrogen peroxide and", "hydrogen peroxide and oxygen", "and oxygen kops", "oxygen kops et", "kops et al. 2002", "al. 2002 hori", "2002 hori et", "hori et al. 2013", "al. 2013 araujo", "2013 araujo et", "araujo et al. 2011", "al. 2011 guan", "2011 guan et", "guan et al. 2016", "et al. 2016 .", "al. 2016 . foxo4", "2016 . foxo4 stimulates", ". foxo4 stimulates sod2", "foxo4 stimulates sod2 gene", "stimulates sod2 gene transcription", "sod2 gene transcription in", "gene transcription in collaboration", "transcription in collaboration with", "in collaboration with atxn3", "with atxn3 a", "atxn3 a protein", "a protein involved in", "protein involved in spinocerebellar", "involved in spinocerebellar ataxia", "in spinocerebellar ataxia type", "spinocerebellar ataxia type 3", "type 3 sca3", "sca3 araujo", "et al. 2011 .", "al. 2011 . foxo3", "2011 . foxo3 and", ". foxo3 and foxo6", "and foxo6 and", "foxo6 and possibly", "transcription of the cat", "of the cat gene", "cat gene encoding", "gene encoding catalase", "encoding catalase an", "catalase an enzyme", "an enzyme that converts", "enzyme that converts hydrogen", "that converts hydrogen peroxide", "converts hydrogen peroxide to", "hydrogen peroxide to water", "peroxide to water and", "to water and oxygen", "and oxygen thus", "oxygen thus protecting", "thus protecting cells from", "protecting cells from the", "cells from the oxidative", "from the oxidative stress", "oxidative stress awad", "stress awad et", "awad et al. 2014", "al. 2014 kim", "2014 kim et", "kim et al. 2014", "al. 2014 rangarajan", "2014 rangarajan et", "rangarajan et al. 2015", "al. 2015 song", "2015 song et", "song et al. 2016", "al. 2016 liao", "2016 liao et", "liao et al. 2016", "al. 2016 guo", "2016 guo et", "guo et al. 2016", "al. 2016 .
foxo transcription", "2016 .
foxo transcription factors", ".
foxo transcription factors regulate", "transcription factors regulate transcription", "factors regulate transcription of", "regulate transcription of several", "transcription of several genes", "of several genes whose", "several genes whose protein", "genes whose protein products", "whose protein products are", "protein products are secreted", "products are secreted from", "are secreted from hypothalamic", "secreted from hypothalamic neurons", "from hypothalamic neurons to", "hypothalamic neurons to control", "neurons to control appetite", "to control appetite and", "control appetite and food", "appetite and food intake:", "and food intake: npy", "food intake: npy gene", "npy gene agrp", "gene agrp gene", "agrp gene and pomc", "gene and pomc gene.", "and pomc gene. at", "pomc gene. at low", "gene. at low insulin", "at low insulin levels", "insulin levels characteristic", "levels characteristic of", "of starvation foxo", "starvation foxo transcription", "foxo transcription factors bind", "transcription factors bind to", "factors bind to insulin", "bind to insulin responsive", "to insulin responsive elements", "responsive elements ires", "ires in the", "in the regulatory regions", "the regulatory regions of", "regulatory regions of npy", "of npy agrp", "npy agrp and", "agrp and pomc gene.", "and pomc gene. foxo1", "pomc gene. foxo1 directly", "gene. foxo1 directly stimulates", "foxo1 directly stimulates transcription", "stimulates transcription of the", "transcription of the npy", "of the npy gene", "npy gene encoding", "gene encoding neuropeptide", "neuropeptide y kim", "y kim et", "kim et al. 2006", "al. 2006 hong", "2006 hong et", "hong et al. 2012", "2012 and", "and the agrp gene", "agrp gene encoding", "gene encoding agouti", "encoding agouti related protein", "related protein kitamura", "protein kitamura et", "kitamura et al. 2006", "al. 2006 kim", "2006 kim et", "2006 which", "which both stimulate food", "both stimulate food intake.", "stimulate food intake. at", "food intake. at the", "intake. at the same", "at the same time", "same time foxo1", "time foxo1 directly", "foxo1 directly represses transcription", "directly represses transcription of", "represses transcription of the", "transcription of the pomc", "of the pomc gene", "pomc gene encoding", "gene encoding melanocyte", "encoding melanocyte stimulating hormone", "melanocyte stimulating hormone alpha", "alpha which", "which suppresses food intake", "food intake kitamura", "intake kitamura et", "et al. 2006 .", "al. 2006 . when", ". when upon", "when upon food", "food intake blood", "intake blood insulin", "blood insulin levels rise", "levels rise insulin", "rise insulin mediated", "insulin mediated activation of", "mediated activation of pi3k/akt", "activation of pi3k/akt signaling", "of pi3k/akt signaling inhibits", "pi3k/akt signaling inhibits foxo", "signaling inhibits foxo transcriptional", "inhibits foxo transcriptional activity.
in", "foxo transcriptional activity.
in liver", "transcriptional activity.
in liver cells", "liver cells foxo", "cells foxo transcription", "foxo transcription factors regulate", "regulate transcription of genes", "transcription of genes involved", "genes involved in gluconeogenesis:", "involved in gluconeogenesis: g6pc", "in gluconeogenesis: g6pc gene", "g6pc gene encoding", "gene encoding glucose", "encoding glucose 6 phosphatase", "glucose 6 phosphatase and", "6 phosphatase and pck1", "phosphatase and pck1 gene", "pck1 gene encoding", "gene encoding phosphoenolpyruvate", "encoding phosphoenolpyruvate carboxykinase. actions", "phosphoenolpyruvate carboxykinase. actions of", "carboxykinase. actions of g6pc", "actions of g6pc and", "of g6pc and pck1", "g6pc and pck1 enable", "and pck1 enable steady", "pck1 enable steady glucose", "enable steady glucose blood", "steady glucose blood levels", "glucose blood levels during", "blood levels during fasting.", "levels during fasting. foxo1", "fasting. foxo1 foxo3", "foxo1 foxo3 and", "foxo3 and foxo4 directly", "and foxo4 directly stimulate", "foxo4 directly stimulate pck1", "directly stimulate pck1 gene", "stimulate pck1 gene transcription", "gene transcription hall", "transcription hall et", "hall et al. 2000", "al. 2000 yang", "2000 yang et", "yang et al. 2002", "al. 2002 puigserver", "2002 puigserver et", "puigserver et al. 2003", "2003 while", "while all four foxos", "four foxos foxo1", "foxo3 foxo4 and", "foxo4 and foxo6 directly", "and foxo6 directly stimulate", "foxo6 directly stimulate g6pc", "directly stimulate g6pc gene", "stimulate g6pc gene transcription", "gene transcription yang", "transcription yang et", "al. 2003 onuma", "2003 onuma et", "onuma et al. 2006", "kim et al. 2011", "al. 2011 . foxo", "2011 . foxo mediated", ". foxo mediated induction", "foxo mediated induction of", "mediated induction of g6pc", "induction of g6pc and", "g6pc and pck1 genes", "and pck1 genes is", "pck1 genes is negatively", "genes is negatively regulated", "is negatively regulated by", "negatively regulated by insulin", "regulated by insulin induced", "by insulin induced pi3k/akt", "insulin induced pi3k/akt signaling.
foxo1", "pi3k/akt signaling.
foxo1 foxo3", "signaling.
foxo1 foxo3 and", "foxo4 directly stimulate transcription", "transcription of the igfbp1", "of the igfbp1 gene", "igfbp1 gene encoding", "gene encoding insulin", "encoding insulin growth factor", "insulin growth factor binding", "growth factor binding protein", "factor binding protein 2", "protein 2 tang", "2 tang et", "tang et al. 1999", "al. 1999 kops", "1999 kops et", "kops et al. 1999", "al. 1999 hall", "1999 hall et", "2002 which", "which increases sensitivity of", "increases sensitivity of cells", "sensitivity of cells to", "of cells to insulin.
foxo1", "cells to insulin.
foxo1 and", "to insulin.
foxo1 and foxo3", "insulin.
foxo1 and foxo3 directly", "and foxo3 directly stimulate", "foxo3 directly stimulate transcription", "transcription of the abca6", "the abca6 atp", "abca6 atp binding", "atp binding cassette sub", "binding cassette sub family", "cassette sub family a", "sub family a member", "family a member 6", "member 6 gene", "encoding a putative transporter", "a putative transporter protein", "putative transporter protein that", "transporter protein that is", "protein that is thought", "that is thought to", "is thought to be", "thought to be involved", "to be involved in", "be involved in lipid", "involved in lipid homeostasis", "lipid homeostasis gai", "homeostasis gai et", "gai et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the gck", "the gck glucokinase", "glucokinase gene is", "gene is another gene", "is another gene involved", "another gene involved in", "gene involved in lipid", "in lipid homeostasis that", "lipid homeostasis that is", "homeostasis that is regulated", "that is regulated by", "is regulated by foxos.", "regulated by foxos. foxo1", "foxos. foxo1 acting", "foxo1 acting with", "acting with the sin3a:hdac", "with the sin3a:hdac complex", "sin3a:hdac complex directly", "complex directly represses", "directly represses the gck", "represses the gck gene", "the gck gene transcription", "gene transcription thus", "transcription thus repressing", "thus repressing lipogenesis in", "repressing lipogenesis in the", "lipogenesis in the absence", "in the absence of", "the absence of insulin", "of insulin langlet", "insulin langlet et", "langlet et al. 2017", "et al. 2017 .", "al. 2017 . the", "2017 . the srebf1", "the srebf1 srebp1", "gene which encodes", "which encodes a transcriptional", "encodes a transcriptional activator", "a transcriptional activator required", "transcriptional activator required for", "activator required for lipid", "required for lipid homeostasis", "lipid homeostasis is", "homeostasis is directly", "is directly transcriptionally repressed", "directly transcriptionally repressed by", "transcriptionally repressed by foxo1", "by foxo1 deng", "foxo1 deng et", "deng et al. 2012", "et al. 2012 .", "al. 2012 . transcription", "2012 . transcription of", ". transcription of the", "transcription of the retn", "of the retn gene", "retn gene encoding", "gene encoding resistin", "encoding resistin an", "resistin an adipocyte", "an adipocyte specific hormone", "adipocyte specific hormone that", "specific hormone that suppresses", "hormone that suppresses insulin", "that suppresses insulin mediated", "suppresses insulin mediated uptake", "insulin mediated uptake of", "mediated uptake of glucose", "uptake of glucose by", "of glucose by adipose", "glucose by adipose cells", "adipose cells is", "cells is directly", "is directly stimulated by", "directly stimulated by foxo1", "by foxo1 liu", "foxo1 liu et", "liu et al. 2014", "et al. 2014 .
transcription", "al. 2014 .
transcription of", "2014 .
transcription of two", ".
transcription of two genes", "of two genes encoding", "two genes encoding e3", "genes encoding e3 ubiquitin", "encoding e3 ubiquitin ligases", "e3 ubiquitin ligases fbxo32", "ligases fbxo32 atrogin", "fbxo32 atrogin 1", "atrogin 1 and", "1 and trim63", "and trim63 murf1", "murf1 involved", "involved in degradation of", "in degradation of muscle", "degradation of muscle proteins", "of muscle proteins and", "muscle proteins and muscle", "proteins and muscle wasting", "and muscle wasting during", "muscle wasting during starvation", "during starvation is", "starvation is positively", "is positively regulated by", "positively regulated by foxo", "regulated by foxo transcription", "by foxo transcription factors", "transcription factors sandri", "factors sandri et", "sandri et al. 2004", "al. 2004 waddell", "2004 waddell et", "waddell et al. 2008", "al. 2008 raffaello", "2008 raffaello et", "raffaello et al. 2010", "al. 2010 senf", "2010 senf et", "senf et al. 2011", "al. 2011 bollinger", "2011 bollinger et", "bollinger et al. 2014", "al. 2014 wang", "2014 wang et", "wang et al. 2017", "foxo6 the least studied", "the least studied member of", "least studied member of the", "studied member of the foxo", "member of the foxo family", "the foxo family directly", "foxo family directly stimulates", "family directly stimulates transcription", "directly stimulates transcription of plxna4", "stimulates transcription of plxna4 gene", "of plxna4 gene encoding", "plxna4 gene encoding a", "gene encoding a co", "encoding a co factor for", "a co factor for the", "co factor for the semaphorin", "factor for the semaphorin sema3a", "for the semaphorin sema3a receptor.", "the semaphorin sema3a receptor. foxo6", "semaphorin sema3a receptor. foxo6 mediated", "sema3a receptor. foxo6 mediated regulation", "receptor. foxo6 mediated regulation of", "foxo6 mediated regulation of plxna4", "mediated regulation of plxna4 expression", "regulation of plxna4 expression plays", "of plxna4 expression plays an", "plxna4 expression plays an important", "expression plays an important role", "plays an important role in", "an important role in radial", "important role in radial glia", "role in radial glia migration", "in radial glia migration during", "radial glia migration during cortical", "glia migration during cortical development", "during cortical development paap", "cortical development paap et", "development paap et al.", "paap et al. 2016 .
foxo", "et al. 2016 .
foxo mediated", "al. 2016 .
foxo mediated up", "2016 .
foxo mediated up regulation", ".
foxo mediated up regulation of", "mediated up regulation of genes", "up regulation of genes involved", "regulation of genes involved in", "of genes involved in reduction", "genes involved in reduction of", "involved in reduction of the", "in reduction of the oxidative", "reduction of the oxidative stress", "of the oxidative stress burden", "the oxidative stress burden is", "oxidative stress burden is not", "stress burden is not specific", "burden is not specific to", "is not specific to neurons", "specific to neurons but", "to neurons but plays", "neurons but plays an", "but plays an important role", "an important role in neuronal", "important role in neuronal survival", "role in neuronal survival and", "in neuronal survival and neurodegenerative", "neuronal survival and neurodegenerative diseases.", "survival and neurodegenerative diseases. foxo3", "and neurodegenerative diseases. foxo3 and", "neurodegenerative diseases. foxo3 and foxo4", "foxo3 and foxo4 and", "and foxo4 and possibly", "foxo4 and possibly foxo1", "and possibly foxo1 directly", "possibly foxo1 directly stimulate", "foxo1 directly stimulate transcription", "directly stimulate transcription of the", "stimulate transcription of the sod2", "transcription of the sod2 gene", "the sod2 gene encoding", "sod2 gene encoding mitochondrial", "gene encoding mitochondrial manganese", "encoding mitochondrial manganese dependent superoxide", "mitochondrial manganese dependent superoxide dismutase", "dependent superoxide dismutase which", "superoxide dismutase which converts", "dismutase which converts superoxide", "which converts superoxide to the", "converts superoxide to the less", "superoxide to the less harmful", "to the less harmful hydrogen", "the less harmful hydrogen peroxide", "less harmful hydrogen peroxide and", "harmful hydrogen peroxide and oxygen", "peroxide and oxygen kops", "and oxygen kops et", "oxygen kops et al.", "et al. 2002 hori", "al. 2002 hori et", "2002 hori et al.", "et al. 2013 araujo", "al. 2013 araujo et", "2013 araujo et al.", "et al. 2011 guan", "al. 2011 guan et", "2011 guan et al.", "guan et al. 2016 .", "et al. 2016 . foxo4", "al. 2016 . foxo4 stimulates", "2016 . foxo4 stimulates sod2", ". foxo4 stimulates sod2 gene", "foxo4 stimulates sod2 gene transcription", "stimulates sod2 gene transcription in", "sod2 gene transcription in collaboration", "gene transcription in collaboration with", "transcription in collaboration with atxn3", "collaboration with atxn3 a", "with atxn3 a protein", "atxn3 a protein involved", "a protein involved in spinocerebellar", "protein involved in spinocerebellar ataxia", "involved in spinocerebellar ataxia type", "in spinocerebellar ataxia type 3", "ataxia type 3 sca3", "sca3 araujo et", "araujo et al. 2011 .", "et al. 2011 . foxo3", "al. 2011 . foxo3 and", "2011 . foxo3 and foxo6", "foxo3 and foxo6 and", "and foxo6 and possibly", "foxo6 and possibly foxo1", "stimulate transcription of the cat", "transcription of the cat gene", "the cat gene encoding", "cat gene encoding catalase", "encoding catalase an enzyme", "catalase an enzyme that", "an enzyme that converts hydrogen", "enzyme that converts hydrogen peroxide", "that converts hydrogen peroxide to", "converts hydrogen peroxide to water", "hydrogen peroxide to water and", "peroxide to water and oxygen", "water and oxygen thus", "and oxygen thus protecting", "oxygen thus protecting cells", "thus protecting cells from the", "protecting cells from the oxidative", "cells from the oxidative stress", "the oxidative stress awad", "oxidative stress awad et", "stress awad et al.", "et al. 2014 kim", "al. 2014 kim et", "2014 kim et al.", "et al. 2014 rangarajan", "al. 2014 rangarajan et", "2014 rangarajan et al.", "et al. 2015 song", "al. 2015 song et", "2015 song et al.", "et al. 2016 liao", "al. 2016 liao et", "2016 liao et al.", "et al. 2016 guo", "al. 2016 guo et", "2016 guo et al.", "guo et al. 2016 .
foxo", "et al. 2016 .
foxo transcription", "al. 2016 .
foxo transcription factors", "2016 .
foxo transcription factors regulate", ".
foxo transcription factors regulate transcription", "transcription factors regulate transcription of", "factors regulate transcription of several", "regulate transcription of several genes", "transcription of several genes whose", "of several genes whose protein", "several genes whose protein products", "genes whose protein products are", "whose protein products are secreted", "protein products are secreted from", "products are secreted from hypothalamic", "are secreted from hypothalamic neurons", "secreted from hypothalamic neurons to", "from hypothalamic neurons to control", "hypothalamic neurons to control appetite", "neurons to control appetite and", "to control appetite and food", "control appetite and food intake:", "appetite and food intake: npy", "and food intake: npy gene", "intake: npy gene agrp", "npy gene agrp gene", "gene agrp gene and", "agrp gene and pomc gene.", "gene and pomc gene. at", "and pomc gene. at low", "pomc gene. at low insulin", "gene. at low insulin levels", "low insulin levels characteristic", "insulin levels characteristic of", "levels characteristic of starvation", "characteristic of starvation foxo", "of starvation foxo transcription", "starvation foxo transcription factors", "foxo transcription factors bind to", "transcription factors bind to insulin", "factors bind to insulin responsive", "bind to insulin responsive elements", "insulin responsive elements ires", "elements ires in", "ires in the regulatory", "in the regulatory regions of", "the regulatory regions of npy", "regions of npy agrp", "of npy agrp and", "npy agrp and pomc", "agrp and pomc gene. foxo1", "and pomc gene. foxo1 directly", "pomc gene. foxo1 directly stimulates", "gene. foxo1 directly stimulates transcription", "foxo1 directly stimulates transcription of", "directly stimulates transcription of the", "stimulates transcription of the npy", "transcription of the npy gene", "the npy gene encoding", "npy gene encoding neuropeptide", "gene encoding neuropeptide y", "encoding neuropeptide y kim", "neuropeptide y kim et", "y kim et al.", "et al. 2006 hong", "al. 2006 hong et", "2006 hong et al.", "al. 2012 and", "2012 and the", "the agrp gene encoding", "agrp gene encoding agouti", "gene encoding agouti related", "agouti related protein kitamura", "related protein kitamura et", "protein kitamura et al.", "et al. 2006 kim", "al. 2006 kim et", "2006 kim et al.", "al. 2006 which", "2006 which both", "which both stimulate food intake.", "both stimulate food intake. at", "stimulate food intake. at the", "food intake. at the same", "intake. at the same time", "the same time foxo1", "same time foxo1 directly", "time foxo1 directly represses", "foxo1 directly represses transcription of", "directly represses transcription of the", "represses transcription of the pomc", "transcription of the pomc gene", "the pomc gene encoding", "pomc gene encoding melanocyte", "gene encoding melanocyte stimulating", "encoding melanocyte stimulating hormone alpha", "hormone alpha which", "alpha which suppresses", "suppresses food intake kitamura", "food intake kitamura et", "intake kitamura et al.", "kim et al. 2006 .", "et al. 2006 . when", "2006 . when upon", ". when upon food", "when upon food intake", "upon food intake blood", "food intake blood insulin", "intake blood insulin levels", "insulin levels rise insulin", "levels rise insulin mediated", "rise insulin mediated activation", "insulin mediated activation of pi3k/akt", "mediated activation of pi3k/akt signaling", "activation of pi3k/akt signaling inhibits", "of pi3k/akt signaling inhibits foxo", "pi3k/akt signaling inhibits foxo transcriptional", "signaling inhibits foxo transcriptional activity.
in", "inhibits foxo transcriptional activity.
in liver", "foxo transcriptional activity.
in liver cells", "activity.
in liver cells foxo", "liver cells foxo transcription", "cells foxo transcription factors", "foxo transcription factors regulate transcription", "factors regulate transcription of genes", "regulate transcription of genes involved", "transcription of genes involved in", "of genes involved in gluconeogenesis:", "genes involved in gluconeogenesis: g6pc", "involved in gluconeogenesis: g6pc gene", "gluconeogenesis: g6pc gene encoding", "g6pc gene encoding glucose", "gene encoding glucose 6", "encoding glucose 6 phosphatase and", "glucose 6 phosphatase and pck1", "6 phosphatase and pck1 gene", "and pck1 gene encoding", "pck1 gene encoding phosphoenolpyruvate", "gene encoding phosphoenolpyruvate carboxykinase.", "encoding phosphoenolpyruvate carboxykinase. actions of", "phosphoenolpyruvate carboxykinase. actions of g6pc", "carboxykinase. actions of g6pc and", "actions of g6pc and pck1", "of g6pc and pck1 enable", "g6pc and pck1 enable steady", "and pck1 enable steady glucose", "pck1 enable steady glucose blood", "enable steady glucose blood levels", "steady glucose blood levels during", "glucose blood levels during fasting.", "blood levels during fasting. foxo1", "during fasting. foxo1 foxo3", "fasting. foxo1 foxo3 and", "foxo1 foxo3 and foxo4", "foxo3 and foxo4 directly stimulate", "and foxo4 directly stimulate pck1", "foxo4 directly stimulate pck1 gene", "directly stimulate pck1 gene transcription", "pck1 gene transcription hall", "gene transcription hall et", "transcription hall et al.", "et al. 2000 yang", "al. 2000 yang et", "2000 yang et al.", "et al. 2002 puigserver", "al. 2002 puigserver et", "2002 puigserver et al.", "al. 2003 while", "2003 while all", "all four foxos foxo1", "foxos foxo1 foxo3", "foxo1 foxo3 foxo4", "foxo3 foxo4 and foxo6", "foxo4 and foxo6 directly stimulate", "and foxo6 directly stimulate g6pc", "foxo6 directly stimulate g6pc gene", "directly stimulate g6pc gene transcription", "g6pc gene transcription yang", "gene transcription yang et", "transcription yang et al.", "et al. 2003 onuma", "al. 2003 onuma et", "2003 onuma et al.", "kim et al. 2011 .", "et al. 2011 . foxo", "al. 2011 . foxo mediated", "2011 . foxo mediated induction", ". foxo mediated induction of", "foxo mediated induction of g6pc", "mediated induction of g6pc and", "induction of g6pc and pck1", "of g6pc and pck1 genes", "g6pc and pck1 genes is", "and pck1 genes is negatively", "pck1 genes is negatively regulated", "genes is negatively regulated by", "is negatively regulated by insulin", "negatively regulated by insulin induced", "regulated by insulin induced pi3k/akt", "by insulin induced pi3k/akt signaling.
foxo1", "induced pi3k/akt signaling.
foxo1 foxo3", "pi3k/akt signaling.
foxo1 foxo3 and", "signaling.
foxo1 foxo3 and foxo4", "and foxo4 directly stimulate transcription", "foxo4 directly stimulate transcription of", "stimulate transcription of the igfbp1", "transcription of the igfbp1 gene", "the igfbp1 gene encoding", "igfbp1 gene encoding insulin", "gene encoding insulin growth", "encoding insulin growth factor binding", "insulin growth factor binding protein", "growth factor binding protein 2", "binding protein 2 tang", "protein 2 tang et", "2 tang et al.", "et al. 1999 kops", "al. 1999 kops et", "1999 kops et al.", "et al. 1999 hall", "al. 1999 hall et", "1999 hall et al.", "al. 2002 which", "2002 which increases", "which increases sensitivity of cells", "increases sensitivity of cells to", "sensitivity of cells to insulin.
foxo1", "of cells to insulin.
foxo1 and", "cells to insulin.
foxo1 and foxo3", "to insulin.
foxo1 and foxo3 directly", "insulin.
foxo1 and foxo3 directly stimulate", "and foxo3 directly stimulate transcription", "foxo3 directly stimulate transcription of", "stimulate transcription of the abca6", "of the abca6 atp", "the abca6 atp binding", "abca6 atp binding cassette", "atp binding cassette sub family", "binding cassette sub family a", "cassette sub family a member", "sub family a member 6", "a member 6 gene", "6 gene encoding", "gene encoding a putative", "encoding a putative transporter protein", "a putative transporter protein that", "putative transporter protein that is", "transporter protein that is thought", "protein that is thought to", "that is thought to be", "is thought to be involved", "thought to be involved in", "to be involved in lipid", "be involved in lipid homeostasis", "in lipid homeostasis gai", "lipid homeostasis gai et", "homeostasis gai et al.", "gai et al. 2013 .", "et al. 2013 . the", "al. 2013 . the gck", ". the gck glucokinase", "gck glucokinase gene", "glucokinase gene is another", "gene is another gene involved", "is another gene involved in", "another gene involved in lipid", "gene involved in lipid homeostasis", "involved in lipid homeostasis that", "in lipid homeostasis that is", "lipid homeostasis that is regulated", "homeostasis that is regulated by", "that is regulated by foxos.", "is regulated by foxos. foxo1", "by foxos. foxo1 acting", "foxos. foxo1 acting with", "foxo1 acting with the", "acting with the sin3a:hdac complex", "the sin3a:hdac complex directly", "sin3a:hdac complex directly represses", "complex directly represses the", "directly represses the gck gene", "represses the gck gene transcription", "gck gene transcription thus", "gene transcription thus repressing", "transcription thus repressing lipogenesis", "thus repressing lipogenesis in the", "repressing lipogenesis in the absence", "lipogenesis in the absence of", "in the absence of insulin", "absence of insulin langlet", "of insulin langlet et", "insulin langlet et al.", "langlet et al. 2017 .", "et al. 2017 . the", "al. 2017 . the srebf1", ". the srebf1 srebp1", "srebf1 srebp1 gene", "srebp1 gene which", "gene which encodes a", "which encodes a transcriptional activator", "encodes a transcriptional activator required", "a transcriptional activator required for", "transcriptional activator required for lipid", "activator required for lipid homeostasis", "for lipid homeostasis is", "lipid homeostasis is directly", "homeostasis is directly transcriptionally", "is directly transcriptionally repressed by", "directly transcriptionally repressed by foxo1", "repressed by foxo1 deng", "by foxo1 deng et", "foxo1 deng et al.", "deng et al. 2012 .", "et al. 2012 . transcription", "al. 2012 . transcription of", "2012 . transcription of the", ". transcription of the retn", "transcription of the retn gene", "the retn gene encoding", "retn gene encoding resistin", "encoding resistin an adipocyte", "resistin an adipocyte specific", "an adipocyte specific hormone that", "adipocyte specific hormone that suppresses", "specific hormone that suppresses insulin", "hormone that suppresses insulin mediated", "that suppresses insulin mediated uptake", "suppresses insulin mediated uptake of", "insulin mediated uptake of glucose", "mediated uptake of glucose by", "uptake of glucose by adipose", "of glucose by adipose cells", "by adipose cells is", "adipose cells is directly", "cells is directly stimulated", "is directly stimulated by foxo1", "stimulated by foxo1 liu", "by foxo1 liu et", "foxo1 liu et al.", "liu et al. 2014 .
transcription", "et al. 2014 .
transcription of", "al. 2014 .
transcription of two", "2014 .
transcription of two genes", ".
transcription of two genes encoding", "of two genes encoding e3", "two genes encoding e3 ubiquitin", "genes encoding e3 ubiquitin ligases", "encoding e3 ubiquitin ligases fbxo32", "ubiquitin ligases fbxo32 atrogin", "ligases fbxo32 atrogin 1", "atrogin 1 and trim63", "murf1 involved in", "involved in degradation of muscle", "in degradation of muscle proteins", "degradation of muscle proteins and", "of muscle proteins and muscle", "muscle proteins and muscle wasting", "proteins and muscle wasting during", "and muscle wasting during starvation", "wasting during starvation is", "during starvation is positively", "starvation is positively regulated", "is positively regulated by foxo", "positively regulated by foxo transcription", "regulated by foxo transcription factors", "foxo transcription factors sandri", "transcription factors sandri et", "factors sandri et al.", "et al. 2004 waddell", "al. 2004 waddell et", "2004 waddell et al.", "et al. 2008 raffaello", "al. 2008 raffaello et", "2008 raffaello et al.", "et al. 2010 senf", "al. 2010 senf et", "2010 senf et al.", "et al. 2011 bollinger", "al. 2011 bollinger et", "2011 bollinger et al.", "et al. 2014 wang", "al. 2014 wang et", "2014 wang et al.", "wang et al. 2017 ." ] }, { "record_id": "GLY_000594_1_694", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9615710", "r hsa", "hsa 9615710", "r hsa 9615710" ] }, { "record_id": "GLY_000594_1_694", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "late endosomal", "endosomal microautophagy", "late endosomal microautophagy", "is a", "a non", "non selective", "selective autophagic", "autophagic pathway", "pathway that", "that involves", "involves internalisation", "internalisation of", "of cytosolic", "cytosolic cargo", "cargo through", "through invaginations", "invaginations of", "of the", "the lysosomal", "lysosomal membrane.", "membrane. mi", "mi can", "can be", "be induced", "induced by", "by nitrogen", "nitrogen starvation", "starvation and", "and complements", "complements other", "other related", "related self", "self eating", "eating processes", "processes such", "such as", "as macroautophagy", "and chaperone", "chaperone mediated", "mediated autophagy", "cma .", ". mi", "can degrade", "degrade cell", "cell organelles", "organelles and", "and bulk", "bulk cytosolic", "cytosolic proteins", "proteins directly", "directly via", "via the", "the lysosome", "lysosome and", "and late", "late endosome.", "endosome. mi", "can also", "also target", "target substrates", "substrates with", "with kferq", "kferq motifs", "motifs with", "with the", "the help", "help of", "of hspa8", "li w", "w w", "w et", "et al.", "al. 2012", "2012 .", "microautophagy mi", "mi is", "is a non", "a non selective", "non selective autophagic", "selective autophagic pathway", "autophagic pathway that", "pathway that involves", "that involves internalisation", "involves internalisation of", "internalisation of cytosolic", "of cytosolic cargo", "cytosolic cargo through", "cargo through invaginations", "through invaginations of", "invaginations of the", "of the lysosomal", "the lysosomal membrane.", "lysosomal membrane. mi", "membrane. mi can", "mi can be", "can be induced", "be induced by", "induced by nitrogen", "by nitrogen starvation", "nitrogen starvation and", "starvation and complements", "and complements other", "complements other related", "other related self", "related self eating", "self eating processes", "eating processes such", "processes such as", "such as macroautophagy", "macroautophagy ma", "ma and", "and chaperone mediated", "chaperone mediated autophagy", "autophagy cma", "cma . mi", ". mi can", "mi can degrade", "can degrade cell", "degrade cell organelles", "cell organelles and", "organelles and bulk", "and bulk cytosolic", "bulk cytosolic proteins", "cytosolic proteins directly", "proteins directly via", "directly via the", "via the lysosome", "the lysosome and", "lysosome and late", "and late endosome.", "late endosome. mi", "endosome. mi can", "mi can also", "can also target", "also target substrates", "target substrates with", "substrates with kferq", "with kferq motifs", "kferq motifs with", "motifs with the", "with the help", "the help of", "help of hspa8", "hspa8 li", "li w w", "w w et", "w et al.", "et al. 2012", "al. 2012 .", "mi is a", "is a non selective", "a non selective autophagic", "non selective autophagic pathway", "selective autophagic pathway that", "autophagic pathway that involves", "pathway that involves internalisation", "that involves internalisation of", "involves internalisation of cytosolic", "internalisation of cytosolic cargo", "of cytosolic cargo through", "cytosolic cargo through invaginations", "cargo through invaginations of", "through invaginations of the", "invaginations of the lysosomal", "of the lysosomal membrane.", "the lysosomal membrane. mi", "lysosomal membrane. mi can", "membrane. mi can be", "mi can be induced", "can be induced by", "be induced by nitrogen", "induced by nitrogen starvation", "by nitrogen starvation and", "nitrogen starvation and complements", "starvation and complements other", "and complements other related", "complements other related self", "other related self eating", "related self eating processes", "self eating processes such", "eating processes such as", "processes such as macroautophagy", "as macroautophagy ma", "ma and chaperone", "and chaperone mediated autophagy", "mediated autophagy cma", "autophagy cma .", "cma . mi can", ". mi can degrade", "mi can degrade cell", "can degrade cell organelles", "degrade cell organelles and", "cell organelles and bulk", "organelles and bulk cytosolic", "and bulk cytosolic proteins", "bulk cytosolic proteins directly", "cytosolic proteins directly via", "proteins directly via the", "directly via the lysosome", "via the lysosome and", "the lysosome and late", "lysosome and late endosome.", "and late endosome. mi", "late endosome. mi can", "endosome. mi can also", "mi can also target", "can also target substrates", "also target substrates with", "target substrates with kferq", "substrates with kferq motifs", "with kferq motifs with", "kferq motifs with the", "motifs with the help", "with the help of", "the help of hspa8", "of hspa8 li", "hspa8 li w", "li w w et", "w w et al.", "w et al. 2012", "et al. 2012 .", "microautophagy mi is", "mi is a non", "is a non selective autophagic", "a non selective autophagic pathway", "non selective autophagic pathway that", "selective autophagic pathway that involves", "autophagic pathway that involves internalisation", "pathway that involves internalisation of", "that involves internalisation of cytosolic", "involves internalisation of cytosolic cargo", "internalisation of cytosolic cargo through", "of cytosolic cargo through invaginations", "cytosolic cargo through invaginations of", "cargo through invaginations of the", "through invaginations of the lysosomal", "invaginations of the lysosomal membrane.", "of the lysosomal membrane. mi", "the lysosomal membrane. mi can", "lysosomal membrane. mi can be", "membrane. mi can be induced", "mi can be induced by", "can be induced by nitrogen", "be induced by nitrogen starvation", "induced by nitrogen starvation and", "by nitrogen starvation and complements", "nitrogen starvation and complements other", "starvation and complements other related", "and complements other related self", "complements other related self eating", "other related self eating processes", "related self eating processes such", "self eating processes such as", "eating processes such as macroautophagy", "such as macroautophagy ma", "macroautophagy ma and", "ma and chaperone mediated", "chaperone mediated autophagy cma", "mediated autophagy cma .", "autophagy cma . mi", "cma . mi can degrade", ". mi can degrade cell", "mi can degrade cell organelles", "can degrade cell organelles and", "degrade cell organelles and bulk", "cell organelles and bulk cytosolic", "organelles and bulk cytosolic proteins", "and bulk cytosolic proteins directly", "bulk cytosolic proteins directly via", "cytosolic proteins directly via the", "proteins directly via the lysosome", "directly via the lysosome and", "via the lysosome and late", "the lysosome and late endosome.", "lysosome and late endosome. mi", "and late endosome. mi can", "late endosome. mi can also", "endosome. mi can also target", "mi can also target substrates", "can also target substrates with", "also target substrates with kferq", "target substrates with kferq motifs", "substrates with kferq motifs with", "with kferq motifs with the", "kferq motifs with the help", "motifs with the help of", "with the help of hspa8", "help of hspa8 li", "of hspa8 li w", "hspa8 li w w", "li w w et al.", "w w et al. 2012", "w et al. 2012 ." ] }, { "record_id": "GLY_000594_1_695", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9617324", "r hsa", "hsa 9617324", "r hsa 9617324" ] }, { "record_id": "GLY_000594_1_695", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of nmda", "nmda receptor", "receptor mediated", "mediated neuronal", "neuronal transmission", "negative regulation of", "regulation of nmda", "of nmda receptor", "nmda receptor mediated", "receptor mediated neuronal", "mediated neuronal transmission", "negative regulation of nmda", "regulation of nmda receptor", "of nmda receptor mediated", "nmda receptor mediated neuronal", "receptor mediated neuronal transmission", "negative regulation of nmda receptor", "regulation of nmda receptor mediated", "of nmda receptor mediated neuronal", "nmda receptor mediated neuronal transmission", "the duration", "duration of", "transmission can", "can be", "be limited", "limited by", "by binding", "binding of", "of the", "the activated", "activated calmodulin", "calmodulin to", "to the", "activated nmda", "nmda receptor.", "receptor. in", "in addition", "addition to", "to shortening", "shortening the", "the nmda", "nmda channel", "channel pore", "pore open", "open state", "calmodulin interferes", "interferes with", "with actn2", "actn2 mediated", "mediated anchoring", "anchoring of", "nmda receptors", "receptors to", "the postsynaptic", "postsynaptic density", "ehlers et", "et al.", "al. 1996", "wyszynski et", "al. 1997", "1997 .", ". protein", "protein phosphatases", "phosphatases ppm1e", "ppm1e and", "and ppm1f", "ppm1f dephosphorylate", "dephosphorylate activated", "activated calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinases", "thus halting", "halting camk", "camk mediated", "mediated signaling", "okuno et", "al. 1998", "ishida et", "kitani et", "al. 2003", "2003 .", "the duration of", "duration of nmda", "neuronal transmission can", "transmission can be", "can be limited", "be limited by", "limited by binding", "by binding of", "binding of the", "of the activated", "the activated calmodulin", "activated calmodulin to", "calmodulin to the", "to the activated", "the activated nmda", "activated nmda receptor.", "nmda receptor. in", "receptor. in addition", "in addition to", "addition to shortening", "to shortening the", "shortening the nmda", "the nmda channel", "nmda channel pore", "channel pore open", "pore open state", "state calmodulin", "calmodulin interferes with", "interferes with actn2", "with actn2 mediated", "actn2 mediated anchoring", "mediated anchoring of", "anchoring of nmda", "of nmda receptors", "nmda receptors to", "receptors to the", "to the postsynaptic", "the postsynaptic density", "density ehlers", "ehlers et al.", "et al. 1996", "1996 wyszynski", "wyszynski et al.", "et al. 1997", "al. 1997 .", "1997 . protein", ". protein phosphatases", "protein phosphatases ppm1e", "phosphatases ppm1e and", "ppm1e and ppm1f", "and ppm1f dephosphorylate", "ppm1f dephosphorylate activated", "dephosphorylate activated calcium/calmodulin", "activated calcium/calmodulin dependent", "calcium/calmodulin dependent kinases", "kinases camks", "thus halting camk", "halting camk mediated", "camk mediated signaling", "signaling ishida", "ishida okuno", "okuno et al.", "et al. 1998", "1998 ishida", "ishida et al.", "1998 kitani", "kitani et al.", "et al. 2003", "al. 2003 .", "the duration of nmda", "duration of nmda receptor", "mediated neuronal transmission can", "neuronal transmission can be", "transmission can be limited", "can be limited by", "be limited by binding", "limited by binding of", "by binding of the", "binding of the activated", "of the activated calmodulin", "the activated calmodulin to", "activated calmodulin to the", "calmodulin to the activated", "to the activated nmda", "the activated nmda receptor.", "activated nmda receptor. in", "nmda receptor. in addition", "receptor. in addition to", "in addition to shortening", "addition to shortening the", "to shortening the nmda", "shortening the nmda channel", "the nmda channel pore", "nmda channel pore open", "channel pore open state", "open state calmodulin", "state calmodulin interferes", "calmodulin interferes with actn2", "interferes with actn2 mediated", "with actn2 mediated anchoring", "actn2 mediated anchoring of", "mediated anchoring of nmda", "anchoring of nmda receptors", "of nmda receptors to", "nmda receptors to the", "receptors to the postsynaptic", "to the postsynaptic density", "postsynaptic density ehlers", "density ehlers et", "ehlers et al. 1996", "al. 1996 wyszynski", "1996 wyszynski et", "wyszynski et al. 1997", "et al. 1997 .", "al. 1997 . protein", "1997 . protein phosphatases", ". protein phosphatases ppm1e", "protein phosphatases ppm1e and", "phosphatases ppm1e and ppm1f", "ppm1e and ppm1f dephosphorylate", "and ppm1f dephosphorylate activated", "ppm1f dephosphorylate activated calcium/calmodulin", "dephosphorylate activated calcium/calmodulin dependent", "activated calcium/calmodulin dependent kinases", "dependent kinases camks", "camks thus", "thus halting camk mediated", "halting camk mediated signaling", "mediated signaling ishida", "ishida okuno et", "okuno et al. 1998", "al. 1998 ishida", "1998 ishida et", "ishida et al. 1998", "al. 1998 kitani", "1998 kitani et", "kitani et al. 2003", "et al. 2003 .", "the duration of nmda receptor", "duration of nmda receptor mediated", "receptor mediated neuronal transmission can", "mediated neuronal transmission can be", "neuronal transmission can be limited", "transmission can be limited by", "can be limited by binding", "be limited by binding of", "limited by binding of the", "by binding of the activated", "binding of the activated calmodulin", "of the activated calmodulin to", "the activated calmodulin to the", "activated calmodulin to the activated", "calmodulin to the activated nmda", "to the activated nmda receptor.", "the activated nmda receptor. in", "activated nmda receptor. in addition", "nmda receptor. in addition to", "receptor. in addition to shortening", "in addition to shortening the", "addition to shortening the nmda", "to shortening the nmda channel", "shortening the nmda channel pore", "the nmda channel pore open", "nmda channel pore open state", "pore open state calmodulin", "open state calmodulin interferes", "state calmodulin interferes with", "calmodulin interferes with actn2 mediated", "interferes with actn2 mediated anchoring", "with actn2 mediated anchoring of", "actn2 mediated anchoring of nmda", "mediated anchoring of nmda receptors", "anchoring of nmda receptors to", "of nmda receptors to the", "nmda receptors to the postsynaptic", "receptors to the postsynaptic density", "the postsynaptic density ehlers", "postsynaptic density ehlers et", "density ehlers et al.", "et al. 1996 wyszynski", "al. 1996 wyszynski et", "1996 wyszynski et al.", "wyszynski et al. 1997 .", "et al. 1997 . protein", "al. 1997 . protein phosphatases", "1997 . protein phosphatases ppm1e", ". protein phosphatases ppm1e and", "protein phosphatases ppm1e and ppm1f", "phosphatases ppm1e and ppm1f dephosphorylate", "ppm1e and ppm1f dephosphorylate activated", "and ppm1f dephosphorylate activated calcium/calmodulin", "ppm1f dephosphorylate activated calcium/calmodulin dependent", "dephosphorylate activated calcium/calmodulin dependent kinases", "calcium/calmodulin dependent kinases camks", "camks thus halting", "thus halting camk mediated signaling", "camk mediated signaling ishida", "signaling ishida okuno", "ishida okuno et al.", "et al. 1998 ishida", "al. 1998 ishida et", "1998 ishida et al.", "et al. 1998 kitani", "al. 1998 kitani et", "1998 kitani et al.", "kitani et al. 2003 ." ] }, { "record_id": "GLY_000594_1_696", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9617828", "r hsa", "hsa 9617828", "r hsa 9617828" ] }, { "record_id": "GLY_000594_1_696", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "foxo mediated", "mediated transcription", "transcription of", "of cell", "cell cycle", "cycle genes", "foxo mediated transcription", "mediated transcription of", "transcription of cell", "of cell cycle", "cell cycle genes", "foxo mediated transcription of", "mediated transcription of cell", "transcription of cell cycle", "of cell cycle genes", "foxo mediated transcription of cell", "mediated transcription of cell cycle", "transcription of cell cycle genes", "foxo transcription", "transcription factors", "factors induce", "induce expression", "expression of", "of several", "several genes", "genes that", "that negatively", "negatively regulate", "regulate proliferation", "proliferation of", "of different", "different cell", "cell types", "such as", "as erythroid", "erythroid progenitors", "bakker et", "et al.", "al. 2004", "wang et", "al. 2015", "and neuroepithelial", "neuroepithelial progenitor", "progenitor cells", "cells in", "in the", "the telencephalon", "seoane et", "2004 .
transcription", ".
transcription of", "of cyclin", "cyclin dependent", "dependent kinase", "inhibitors cdkn1a", "is directly", "directly stimulated", "stimulated by", "by foxo1", "foxo3 and", "and foxo4", "tinkum et", "al. 2013", "2013 .", ". foxo", "factors can", "can cooperate", "cooperate with", "with the", "the smad2/3:smad4", "smad2/3:smad4 complex", "complex to", "to induce", "induce cdkn1a", "cdkn1a transcription", "transcription in", "in response", "response to", "to tgf", "tgf beta", "beta signaling", "2004 .
foxo", ".
foxo transcription", "factors foxo1", "foxo4 stimulate", "stimulate transcription", "of the", "the cdkn1b", "but direct", "direct binding", "binding of", "of foxos", "foxos to", "to the", "cdkn1b gene", "gene locus", "locus has", "has not", "not been", "been demonstrated", "dijkers et", "al. 2000", "medema et", "lees et", "al. 2008", "2008 .
foxo3", ".
foxo3 and", "and possibly", "possibly foxo1", "directly stimulate", "the gadd45a", "tran et", "al. 2002", "furukawa hibi", "hibi et", "hughes et", "al. 2011", "sengupta et", "ju et", "al. 2014", "2014 .
transcription", "the retinoblastoma", "retinoblastoma family", "family protein", "protein rbl2", "involved in", "the maintenance", "maintenance of", "of quiescent", "kops et", "chen et", "al. 2006", "2006 .
transcription", "the anti", "anti proliferative", "proliferative protein", "protein ccng2", "ccng2 is", "foxo1 and", "and foxo3", "possibly foxo4", "martinez gac", "gac et", "2006 .", ". transcription", "protein btg1", "btg1 is", "by foxo3", "al. 2007", "2015 .
transcription", "of cav1", "encoding caveolin", "caveolin 1", "in negative", "negative regulation", "regulation of", "of growth", "growth factor", "factor receptor", "receptor signaling", "signaling and", "and establishment", "establishment of", "quiescent cell", "cell phenotype", "van den", "den heuvel", "heuvel et", "al. 2005", "roy et", "nho et", "sisci et", "2013 .
foxo1", ".
foxo1 and", "foxo3 promote", "promote transcription", "the klf4", "klf4 gene", "encoding a", "a transcription", "transcription factor", "factor krueppel", "krueppel like", "like factor", "factor 4", "which inhibits", "inhibits proliferation", "of mouse", "mouse b", "b cells", "yusuf et", "2008 .
", ".
foxo1", "together with", "the p", "p 2s", "2s smad2/3:smad4", "stimulates transcription", "the mstn", "mstn gene", "encoding myostatin", "a tgf", "beta family", "family member", "member that", "that stimulates", "stimulates differentiation", "differentiation of", "of myoblasts", "allen and", "and unterman", "unterman 2007", "2007 .", "foxo transcription factors", "transcription factors induce", "factors induce expression", "induce expression of", "expression of several", "of several genes", "several genes that", "genes that negatively", "that negatively regulate", "negatively regulate proliferation", "regulate proliferation of", "proliferation of different", "of different cell", "different cell types", "types such", "such as erythroid", "as erythroid progenitors", "progenitors bakker", "bakker et al.", "et al. 2004", "2004 wang", "wang et al.", "et al. 2015", "2015 and", "and neuroepithelial progenitor", "neuroepithelial progenitor cells", "progenitor cells in", "cells in the", "in the telencephalon", "telencephalon seoane", "seoane et al.", "al. 2004 .
transcription", "2004 .
transcription of", ".
transcription of cyclin", "of cyclin dependent", "cyclin dependent kinase", "kinase cdk", "cdk inhibitors", "cdkn1a p21cip1", "p21cip1 is", "is directly stimulated", "directly stimulated by", "stimulated by foxo1", "foxo1 foxo3", "foxo3 and foxo4", "foxo4 seoane", "2004 tinkum", "tinkum et al.", "et al. 2013", "al. 2013 .", "2013 . foxo", ". foxo transcription", "transcription factors can", "factors can cooperate", "can cooperate with", "cooperate with the", "with the smad2/3:smad4", "the smad2/3:smad4 complex", "smad2/3:smad4 complex to", "complex to induce", "to induce cdkn1a", "induce cdkn1a transcription", "cdkn1a transcription in", "transcription in response", "in response to", "response to tgf", "to tgf beta", "tgf beta signaling", "signaling seoane", "al. 2004 .
foxo", "2004 .
foxo transcription", ".
foxo transcription factors", "transcription factors foxo1", "and foxo4 stimulate", "foxo4 stimulate transcription", "stimulate transcription of", "transcription of the", "of the cdkn1b", "cdkn1b p27kip1", "p27kip1 gene", "gene but", "but direct binding", "direct binding of", "binding of foxos", "of foxos to", "foxos to the", "to the cdkn1b", "the cdkn1b gene", "cdkn1b gene locus", "gene locus has", "locus has not", "has not been", "not been demonstrated", "demonstrated dijkers", "dijkers et al.", "et al. 2000", "2000 medema", "medema et al.", "2000 lees", "lees et al.", "et al. 2008", "al. 2008 .
foxo3", "2008 .
foxo3 and", ".
foxo3 and foxo4", "foxo4 and", "and possibly foxo1", "foxo1 directly", "directly stimulate transcription", "of the gadd45a", "gadd45a gene", "gene tran", "tran et al.", "et al. 2002", "2002 furukawa", "furukawa hibi et", "hibi et al.", "2002 hughes", "hughes et al.", "et al. 2011", "2011 sengupta", "sengupta et al.", "2011 ju", "ju et al.", "et al. 2014", "al. 2014 .
transcription", "2014 .
transcription of", ".
transcription of the", "of the retinoblastoma", "the retinoblastoma family", "retinoblastoma family protein", "family protein rbl2", "rbl2 p130", "involved in the", "in the maintenance", "the maintenance of", "maintenance of quiescent", "quiescent g0", "g0 state", "state is", "foxo4 kops", "kops et al.", "2002 chen", "chen et al.", "et al. 2006", "al. 2006 .
transcription", "2006 .
transcription of", "of the anti", "the anti proliferative", "anti proliferative protein", "proliferative protein ccng2", "protein ccng2 is", "ccng2 is directly", "by foxo1 and", "foxo1 and foxo3", "and possibly foxo4", "foxo4 martinez", "martinez gac et", "gac et al.", "2004 chen", "al. 2006 .", "2006 . transcription", ". transcription of", "proliferative protein btg1", "protein btg1 is", "btg1 is directly", "stimulated by foxo3", "foxo3 bakker", "2004 bakker", "et al. 2007", "2007 wang", "al. 2015 .
transcription", "2015 .
transcription of", ".
transcription of cav1", "cav1 encoding", "encoding caveolin 1", "1 involved", "involved in negative", "in negative regulation", "negative regulation of", "regulation of growth", "of growth factor", "growth factor receptor", "factor receptor signaling", "receptor signaling and", "signaling and establishment", "and establishment of", "establishment of quiescent", "of quiescent cell", "quiescent cell phenotype", "phenotype is", "foxo3 van", "van den heuvel", "den heuvel et", "heuvel et al.", "et al. 2005", "2005 roy", "roy et al.", "2008 nho", "nho et al.", "2013 sisci", "sisci et al.", "al. 2013 .
foxo1", "2013 .
foxo1 and", ".
foxo1 and foxo3", "and foxo3 promote", "foxo3 promote transcription", "promote transcription of", "of the klf4", "the klf4 gene", "gene encoding", "encoding a transcription", "a transcription factor", "transcription factor krueppel", "factor krueppel like", "krueppel like factor", "like factor 4", "4 which", "which inhibits proliferation", "inhibits proliferation of", "proliferation of mouse", "of mouse b", "mouse b cells", "cells yusuf", "yusuf et al.", "al. 2008 .
", "2008 .
foxo1", "foxo1 together", "together with the", "with the p", "the p 2s", "p 2s smad2/3:smad4", "2s smad2/3:smad4 complex", "complex stimulates", "stimulates transcription of", "of the mstn", "the mstn gene", "myostatin a", "a tgf beta", "tgf beta family", "beta family member", "family member that", "member that stimulates", "that stimulates differentiation", "stimulates differentiation of", "differentiation of myoblasts", "myoblasts allen", "allen and unterman", "and unterman 2007", "unterman 2007 .", "foxo transcription factors induce", "transcription factors induce expression", "factors induce expression of", "induce expression of several", "expression of several genes", "of several genes that", "several genes that negatively", "genes that negatively regulate", "that negatively regulate proliferation", "negatively regulate proliferation of", "regulate proliferation of different", "proliferation of different cell", "of different cell types", "cell types such", "types such as", "such as erythroid progenitors", "erythroid progenitors bakker", "progenitors bakker et", "bakker et al. 2004", "al. 2004 wang", "2004 wang et", "wang et al. 2015", "al. 2015 and", "2015 and neuroepithelial", "and neuroepithelial progenitor cells", "neuroepithelial progenitor cells in", "progenitor cells in the", "cells in the telencephalon", "the telencephalon seoane", "telencephalon seoane et", "seoane et al. 2004", "et al. 2004 .
transcription", "al. 2004 .
transcription of", "2004 .
transcription of cyclin", ".
transcription of cyclin dependent", "of cyclin dependent kinase", "dependent kinase cdk", "cdk inhibitors cdkn1a", "inhibitors cdkn1a p21cip1", "p21cip1 is directly", "is directly stimulated by", "directly stimulated by foxo1", "by foxo1 foxo3", "foxo1 foxo3 and", "and foxo4 seoane", "foxo4 seoane et", "al. 2004 tinkum", "2004 tinkum et", "tinkum et al. 2013", "et al. 2013 .", "al. 2013 . foxo", "2013 . foxo transcription", ". foxo transcription factors", "foxo transcription factors can", "transcription factors can cooperate", "factors can cooperate with", "can cooperate with the", "cooperate with the smad2/3:smad4", "with the smad2/3:smad4 complex", "the smad2/3:smad4 complex to", "smad2/3:smad4 complex to induce", "complex to induce cdkn1a", "to induce cdkn1a transcription", "induce cdkn1a transcription in", "cdkn1a transcription in response", "transcription in response to", "in response to tgf", "response to tgf beta", "to tgf beta signaling", "beta signaling seoane", "signaling seoane et", "et al. 2004 .
foxo", "al. 2004 .
foxo transcription", "2004 .
foxo transcription factors", ".
foxo transcription factors foxo1", "factors foxo1 foxo3", "foxo3 and foxo4 stimulate", "and foxo4 stimulate transcription", "foxo4 stimulate transcription of", "stimulate transcription of the", "transcription of the cdkn1b", "the cdkn1b p27kip1", "gene but direct", "but direct binding of", "direct binding of foxos", "binding of foxos to", "of foxos to the", "foxos to the cdkn1b", "to the cdkn1b gene", "the cdkn1b gene locus", "cdkn1b gene locus has", "gene locus has not", "locus has not been", "has not been demonstrated", "been demonstrated dijkers", "demonstrated dijkers et", "dijkers et al. 2000", "al. 2000 medema", "2000 medema et", "medema et al. 2000", "al. 2000 lees", "2000 lees et", "lees et al. 2008", "et al. 2008 .
foxo3", "al. 2008 .
foxo3 and", "2008 .
foxo3 and foxo4", "and foxo4 and", "foxo4 and possibly", "possibly foxo1 directly", "foxo1 directly stimulate", "directly stimulate transcription of", "transcription of the gadd45a", "the gadd45a gene", "gene tran et", "tran et al. 2002", "al. 2002 furukawa", "2002 furukawa hibi", "furukawa hibi et al.", "hibi et al. 2002", "al. 2002 hughes", "2002 hughes et", "hughes et al. 2011", "al. 2011 sengupta", "2011 sengupta et", "sengupta et al. 2011", "al. 2011 ju", "2011 ju et", "ju et al. 2014", "et al. 2014 .
transcription", "al. 2014 .
transcription of", "2014 .
transcription of the", ".
transcription of the retinoblastoma", "of the retinoblastoma family", "the retinoblastoma family protein", "retinoblastoma family protein rbl2", "protein rbl2 p130", "p130 involved", "involved in the maintenance", "in the maintenance of", "the maintenance of quiescent", "of quiescent g0", "state is directly", "and foxo4 kops", "foxo4 kops et", "kops et al. 2002", "al. 2002 chen", "2002 chen et", "chen et al. 2006", "et al. 2006 .
transcription", "al. 2006 .
transcription of", "2006 .
transcription of the", ".
transcription of the anti", "of the anti proliferative", "the anti proliferative protein", "anti proliferative protein ccng2", "proliferative protein ccng2 is", "protein ccng2 is directly", "ccng2 is directly stimulated", "stimulated by foxo1 and", "by foxo1 and foxo3", "and foxo3 and", "foxo3 and possibly", "possibly foxo4 martinez", "foxo4 martinez gac", "martinez gac et al.", "gac et al. 2004", "al. 2004 chen", "2004 chen et", "et al. 2006 .", "al. 2006 . transcription", "2006 . transcription of", ". transcription of the", "transcription of the anti", "anti proliferative protein btg1", "proliferative protein btg1 is", "protein btg1 is directly", "btg1 is directly stimulated", "directly stimulated by foxo3", "by foxo3 bakker", "foxo3 bakker et", "al. 2004 bakker", "2004 bakker et", "bakker et al. 2007", "al. 2007 wang", "2007 wang et", "et al. 2015 .
transcription", "al. 2015 .
transcription of", "2015 .
transcription of cav1", "of cav1 encoding", "cav1 encoding caveolin", "caveolin 1 involved", "1 involved in", "involved in negative regulation", "in negative regulation of", "negative regulation of growth", "regulation of growth factor", "of growth factor receptor", "growth factor receptor signaling", "factor receptor signaling and", "receptor signaling and establishment", "signaling and establishment of", "and establishment of quiescent", "establishment of quiescent cell", "of quiescent cell phenotype", "cell phenotype is", "phenotype is directly", "and foxo3 van", "foxo3 van den", "van den heuvel et", "den heuvel et al.", "heuvel et al. 2005", "al. 2005 roy", "2005 roy et", "roy et al. 2008", "al. 2008 nho", "2008 nho et", "nho et al. 2013", "al. 2013 sisci", "2013 sisci et", "sisci et al. 2013", "et al. 2013 .
foxo1", "al. 2013 .
foxo1 and", "2013 .
foxo1 and foxo3", ".
foxo1 and foxo3 promote", "and foxo3 promote transcription", "foxo3 promote transcription of", "promote transcription of the", "transcription of the klf4", "of the klf4 gene", "klf4 gene encoding", "gene encoding a", "encoding a transcription factor", "a transcription factor krueppel", "transcription factor krueppel like", "factor krueppel like factor", "krueppel like factor 4", "factor 4 which", "4 which inhibits", "which inhibits proliferation of", "inhibits proliferation of mouse", "proliferation of mouse b", "of mouse b cells", "b cells yusuf", "cells yusuf et", "yusuf et al. 2008", "et al. 2008 .
", "al. 2008 .
foxo1", ".
foxo1 together", "foxo1 together with", "together with the p", "with the p 2s", "the p 2s smad2/3:smad4", "p 2s smad2/3:smad4 complex", "smad2/3:smad4 complex stimulates", "complex stimulates transcription", "stimulates transcription of the", "transcription of the mstn", "of the mstn gene", "mstn gene encoding", "gene encoding myostatin", "encoding myostatin a", "myostatin a tgf", "a tgf beta family", "tgf beta family member", "beta family member that", "family member that stimulates", "member that stimulates differentiation", "that stimulates differentiation of", "stimulates differentiation of myoblasts", "of myoblasts allen", "myoblasts allen and", "allen and unterman 2007", "and unterman 2007 .", "foxo transcription factors induce expression", "transcription factors induce expression of", "factors induce expression of several", "induce expression of several genes", "expression of several genes that", "of several genes that negatively", "several genes that negatively regulate", "genes that negatively regulate proliferation", "that negatively regulate proliferation of", "negatively regulate proliferation of different", "regulate proliferation of different cell", "proliferation of different cell types", "different cell types such", "cell types such as", "types such as erythroid", "as erythroid progenitors bakker", "erythroid progenitors bakker et", "progenitors bakker et al.", "et al. 2004 wang", "al. 2004 wang et", "2004 wang et al.", "et al. 2015 and", "al. 2015 and neuroepithelial", "2015 and neuroepithelial progenitor", "and neuroepithelial progenitor cells in", "neuroepithelial progenitor cells in the", "progenitor cells in the telencephalon", "in the telencephalon seoane", "the telencephalon seoane et", "telencephalon seoane et al.", "seoane et al. 2004 .
transcription", "et al. 2004 .
transcription of", "al. 2004 .
transcription of cyclin", "2004 .
transcription of cyclin dependent", ".
transcription of cyclin dependent kinase", "cyclin dependent kinase cdk", "kinase cdk inhibitors", "cdkn1a p21cip1 is", "p21cip1 is directly stimulated", "is directly stimulated by foxo1", "stimulated by foxo1 foxo3", "by foxo1 foxo3 and", "foxo1 foxo3 and foxo4", "foxo3 and foxo4 seoane", "and foxo4 seoane et", "foxo4 seoane et al.", "et al. 2004 tinkum", "al. 2004 tinkum et", "2004 tinkum et al.", "tinkum et al. 2013 .", "et al. 2013 . foxo", "al. 2013 . foxo transcription", "2013 . foxo transcription factors", ". foxo transcription factors can", "foxo transcription factors can cooperate", "transcription factors can cooperate with", "factors can cooperate with the", "can cooperate with the smad2/3:smad4", "cooperate with the smad2/3:smad4 complex", "with the smad2/3:smad4 complex to", "the smad2/3:smad4 complex to induce", "smad2/3:smad4 complex to induce cdkn1a", "complex to induce cdkn1a transcription", "to induce cdkn1a transcription in", "induce cdkn1a transcription in response", "cdkn1a transcription in response to", "transcription in response to tgf", "in response to tgf beta", "response to tgf beta signaling", "tgf beta signaling seoane", "beta signaling seoane et", "signaling seoane et al.", "seoane et al. 2004 .
foxo", "et al. 2004 .
foxo transcription", "al. 2004 .
foxo transcription factors", "2004 .
foxo transcription factors foxo1", "transcription factors foxo1 foxo3", "factors foxo1 foxo3 and", "foxo3 and foxo4 stimulate transcription", "and foxo4 stimulate transcription of", "foxo4 stimulate transcription of the", "stimulate transcription of the cdkn1b", "of the cdkn1b p27kip1", "cdkn1b p27kip1 gene", "p27kip1 gene but", "gene but direct binding", "but direct binding of foxos", "direct binding of foxos to", "binding of foxos to the", "of foxos to the cdkn1b", "foxos to the cdkn1b gene", "to the cdkn1b gene locus", "the cdkn1b gene locus has", "cdkn1b gene locus has not", "gene locus has not been", "locus has not been demonstrated", "not been demonstrated dijkers", "been demonstrated dijkers et", "demonstrated dijkers et al.", "et al. 2000 medema", "al. 2000 medema et", "2000 medema et al.", "et al. 2000 lees", "al. 2000 lees et", "2000 lees et al.", "lees et al. 2008 .
foxo3", "et al. 2008 .
foxo3 and", "al. 2008 .
foxo3 and foxo4", ".
foxo3 and foxo4 and", "and foxo4 and possibly", "foxo4 and possibly foxo1", "and possibly foxo1 directly", "possibly foxo1 directly stimulate", "foxo1 directly stimulate transcription", "directly stimulate transcription of the", "stimulate transcription of the gadd45a", "of the gadd45a gene", "gadd45a gene tran", "gene tran et al.", "et al. 2002 furukawa", "al. 2002 furukawa hibi", "2002 furukawa hibi et", "furukawa hibi et al. 2002", "et al. 2002 hughes", "al. 2002 hughes et", "2002 hughes et al.", "et al. 2011 sengupta", "al. 2011 sengupta et", "2011 sengupta et al.", "et al. 2011 ju", "al. 2011 ju et", "2011 ju et al.", "ju et al. 2014 .
transcription", "et al. 2014 .
transcription of", "al. 2014 .
transcription of the", "2014 .
transcription of the retinoblastoma", ".
transcription of the retinoblastoma family", "of the retinoblastoma family protein", "the retinoblastoma family protein rbl2", "family protein rbl2 p130", "p130 involved in", "involved in the maintenance of", "in the maintenance of quiescent", "maintenance of quiescent g0", "quiescent g0 state", "g0 state is", "state is directly stimulated", "foxo3 and foxo4 kops", "and foxo4 kops et", "foxo4 kops et al.", "et al. 2002 chen", "al. 2002 chen et", "2002 chen et al.", "chen et al. 2006 .
transcription", "et al. 2006 .
transcription of", "al. 2006 .
transcription of the", "2006 .
transcription of the anti", ".
transcription of the anti proliferative", "of the anti proliferative protein", "the anti proliferative protein ccng2", "anti proliferative protein ccng2 is", "proliferative protein ccng2 is directly", "protein ccng2 is directly stimulated", "ccng2 is directly stimulated by", "directly stimulated by foxo1 and", "stimulated by foxo1 and foxo3", "foxo1 and foxo3 and", "and foxo3 and possibly", "foxo3 and possibly foxo4", "and possibly foxo4 martinez", "possibly foxo4 martinez gac", "foxo4 martinez gac et", "martinez gac et al. 2004", "et al. 2004 chen", "al. 2004 chen et", "2004 chen et al.", "chen et al. 2006 .", "et al. 2006 . transcription", "al. 2006 . transcription of", "2006 . transcription of the", ". transcription of the anti", "transcription of the anti proliferative", "the anti proliferative protein btg1", "anti proliferative protein btg1 is", "proliferative protein btg1 is directly", "protein btg1 is directly stimulated", "btg1 is directly stimulated by", "is directly stimulated by foxo3", "stimulated by foxo3 bakker", "by foxo3 bakker et", "foxo3 bakker et al.", "et al. 2004 bakker", "al. 2004 bakker et", "2004 bakker et al.", "et al. 2007 wang", "al. 2007 wang et", "2007 wang et al.", "wang et al. 2015 .
transcription", "et al. 2015 .
transcription of", "al. 2015 .
transcription of cav1", ".
transcription of cav1 encoding", "of cav1 encoding caveolin", "cav1 encoding caveolin 1", "encoding caveolin 1 involved", "caveolin 1 involved in", "1 involved in negative", "involved in negative regulation of", "in negative regulation of growth", "negative regulation of growth factor", "regulation of growth factor receptor", "of growth factor receptor signaling", "growth factor receptor signaling and", "factor receptor signaling and establishment", "receptor signaling and establishment of", "signaling and establishment of quiescent", "and establishment of quiescent cell", "establishment of quiescent cell phenotype", "quiescent cell phenotype is", "cell phenotype is directly", "phenotype is directly stimulated", "foxo1 and foxo3 van", "and foxo3 van den", "foxo3 van den heuvel", "van den heuvel et al.", "den heuvel et al. 2005", "et al. 2005 roy", "al. 2005 roy et", "2005 roy et al.", "et al. 2008 nho", "al. 2008 nho et", "2008 nho et al.", "et al. 2013 sisci", "al. 2013 sisci et", "2013 sisci et al.", "sisci et al. 2013 .
foxo1", "et al. 2013 .
foxo1 and", "al. 2013 .
foxo1 and foxo3", "2013 .
foxo1 and foxo3 promote", ".
foxo1 and foxo3 promote transcription", "and foxo3 promote transcription of", "foxo3 promote transcription of the", "promote transcription of the klf4", "transcription of the klf4 gene", "the klf4 gene encoding", "klf4 gene encoding a", "gene encoding a transcription", "encoding a transcription factor krueppel", "a transcription factor krueppel like", "transcription factor krueppel like factor", "factor krueppel like factor 4", "like factor 4 which", "factor 4 which inhibits", "4 which inhibits proliferation", "which inhibits proliferation of mouse", "inhibits proliferation of mouse b", "proliferation of mouse b cells", "mouse b cells yusuf", "b cells yusuf et", "cells yusuf et al.", "yusuf et al. 2008 .
", "et al. 2008 .
foxo1", "2008 .
foxo1 together", ".
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amino", ".
amino acids", "by at", "at least", "least 4", "4 mechanisms", "in zhuang", "zhuang et", "al. 2019", "wolfson and", "and sabatini", "yao et", ". 1", "or sestrin2", "binds leucine", "leucine and", "and the", "the sestrin1", "sestrin1 2:leucine", "2:leucine complex", "complex is", "is then", "then released", "released from", "the gator2", "gator2 complex", "allowing gator2", "gator2 to", "to positively", "positively regulate", "mtorc1 activation", "chantranupong et", "parmigiani et", "al. 2015", "wolfson et", "al. 2016", "saxton et", "2016 .", ". 2", "castor1 in", "in a", "a homodimer", "homodimer or", "or a", "a heterodimer", "heterodimer with", "with castor2", "castor2 binds", "binds arginine", "arginine and", "the castor1:arginine", "castor1:arginine complex", "is likewise", "likewise released", "from gator2", "to activate", "activate mtorc1", "gai et", "xia et", ". 3", "a negative", "negative regulator", "regulator of", "binds s", "s adenosylmethionine", "a derivative", "derivative of", "of methionine", "gu et", "of sam", "sam causes", "causes bmt2", "bmt2 to", "to dissociate", "dissociate from", "from gator1", "allowing the", "the activation", "activation of", "mtorc1. 4", "the amino", "amino acid", "acid transporter", "transporter slc38a9", "slc38a9 binds", "and slc38a9", "slc38a9 then", "then acts", "a gef", "gef to", "to convert", "convert rraga", "rraga b:gdp", "b:gdp to", "active form", "rraga b:gtp", "rebsamen et", "wang et", "wyant et", "shen and", "sabatini 2018", ". amino", "acid starvation", "starvation also", "also regulates", "regulates the", "the assembly", "assembly of", "the v0", "v0 and", "and v1", "v1 subunits", "subunits of", "of v", "atpase by", "by an", "an uncharacterized", "uncharacterized mechanism", "stransky and", "and forgac", "forgac 2015", "and v", "atpase is", "required for", "for activation", "mtorc1 by", "by amino", "zoncu et", "al. 2011", "2011 .", ". glutamine", "glutamine activates", "activates mtorc1", "by a", "a mechanism", "mechanism that", "that is", "is independent", "independent of", "rag gtpases", "requires arf1", "but is", "is not", "not yet", "yet fully", "fully elucidated", "jewell et", "2015 .", "the mtorc1 complex", "mtorc1 complex acts", "complex acts as", "acts as an", "as an integrator", "an integrator that", "integrator that regulates", "that regulates translation", "translation lipid", "synthesis autophagy", "autophagy and", "and cell growth", "cell growth in", "growth in response", "in response to", "response to multiple", "to multiple inputs", "inputs notably", "glucose oxygen", "oxygen amino", "acids and", "and growth factors", "growth factors such", "factors such as", "such as insulin", "insulin reviewed", "reviewed in sabatini", "in sabatini 2017", "2017 meng", "meng et al.", "et al. 2018", "2018 kim", "kim and guan", "and guan 2019", "guan 2019 .
mtor", ".
mtor the", "the kinase subunit", "kinase subunit of", "subunit of mtorc1", "mtorc1 is", "is activated by", "activated by interaction", "by interaction with", "interaction with rheb:gtp", "with rheb:gtp at", "rheb:gtp at the", "at the cytosolic", "the cytosolic face", "cytosolic face of", "face of lysosomal", "of lysosomal membrane", "membrane long", "long et al.", "et al. 2005", "2005 tee", "tee et al.", "2005 long", "et al. 2007", "2007 yang", "yang et al.", "et al. 2017", "al. 2017 .", "2017 . recruitment", ". recruitment of", "recruitment of mtorc1", "of mtorc1 to", "mtorc1 to the", "to the lysosomal", "the lysosomal membrane", "lysosomal membrane is", "membrane is intricate", "is intricate and", "intricate and incompletely", "and incompletely understood.", "incompletely understood. at", "understood. at the", "at the center", "the center of", "center of the", "of the system", "the system is", "system is a", "is a complex", "a complex of", "complex of two", "of two small", "two small gtpases", "gtpases the", "the rag heterodimer", "heterodimer rraga", "rraga or rragb", "or rragb bound", "rragb bound to", "bound to rragc", "to rragc or", "rragc or rragd", "or rragd .", "rragd . the", ". the rag", "rag heterodimer is", "heterodimer is tethered", "is tethered to", "tethered to the", "to the membrane", "the membrane by", "membrane by the", "by the ragulator", "the ragulator complex", "complex which", "which also binds", "also binds the", "binds the v", "the v atpase", "v atpase complex.", "atpase complex. the", "complex. the rag", "rag heterodimer acts", "heterodimer acts as", "acts as a", "as a cross", "a cross regulating", "cross regulating switch", "switch with", "with the binding", "the binding of", "binding of gtp", "of gtp by", "gtp by one", "by one subunit", "one subunit inhibiting", "subunit inhibiting the", "inhibiting the exchange", "the exchange of", "exchange of gdp", "of gdp for", "gdp for gtp", "for gtp by", "gtp by the", "by the other", "the other subunit", "subunit shen", "shen et al.", "2017 . the", ". the active", "the active conformation", "active conformation of", "conformation of the", "of the rag", "rag heterodimer that", "heterodimer that recruits", "that recruits mtorc1", "recruits mtorc1 to", "membrane is rraga", "is rraga b:gtp:rragc", "rraga b:gtp:rragc d:gdp", "b:gtp:rragc d:gdp while", "d:gdp while the", "while the inactive", "the inactive conformation", "conformation rraga", "rraga b:gdp:rragc d:gtp", "d:gtp releases", "mtorc1 sancak", "sancak et al.", "et al. 2008", "2008 kim", "kim et al.", "2008 sancak", "et al. 2010", "2010 lawrence", "lawrence et al.", "al. 2018 .", "2018 . gtpase", ". gtpase activating", "gtpase activating proteins", "proteins gaps", "gaps and", "and guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange factors", "factors gefs", "gefs acting", "acting upon the", "upon the rag", "rag heterodimer thereby", "heterodimer thereby regulate", "thereby regulate recruitment", "regulate recruitment of", "recruitment of mtorc1.", "of mtorc1. rheb:gtp", "mtorc1. rheb:gtp at", "at the lysosomal", "lysosomal membrane also", "membrane also binds", "also binds mtorc1", "binds mtorc1 and", "mtorc1 and directly", "and directly activates", "directly activates mtorc1.", "activates mtorc1. during", "mtorc1. during inactivation", "during inactivation of", "inactivation of mtorc1", "of mtorc1 in", "mtorc1 in response", "response to removal", "to removal of", "removal of amino", "of amino acids", "acids the", "the tsc complex", "complex a", "a gap for", "gap for rheb", "rheb is", "is required in", "required in addition", "in addition to", "addition to the", "to the inactive", "the inactive rag", "inactive rag complex", "rag complex to", "complex to release", "to release mtorc1", "release mtorc1 from", "mtorc1 from rheb", "from rheb and", "rheb and hence", "and hence fully", "hence fully release", "fully release mtorc1", "mtorc1 from the", "from the lysosomal", "membrane demetriades", "demetriades et al.", "et al. 2014", "al. 2014 .
amino", "2014 .
amino acids", ".
amino acids regulate", "acids regulate recruitment", "lysosomal membrane by", "membrane by at", "by at least", "at least 4", "least 4 mechanisms", "mechanisms reviewed", "reviewed in zhuang", "in zhuang et", "zhuang et al.", "et al. 2019", "2019 wolfson", "wolfson and sabatini", "and sabatini 2017", "2017 yao", "yao et al.", "2017 . 1", "1 sestrin1", "sestrin1 sesn1", "sesn1 or", "sestrin2 sesn2", "sesn2 binds", "binds leucine and", "leucine and the", "and the sestrin1", "the sestrin1 2:leucine", "sestrin1 2:leucine complex", "2:leucine complex is", "complex is then", "is then released", "then released from", "released from the", "from the gator2", "the gator2 complex", "complex allowing", "allowing gator2 to", "gator2 to positively", "to positively regulate", "positively regulate mtorc1", "regulate mtorc1 activation", "activation chantranupong", "chantranupong et al.", "2014 parmigiani", "parmigiani et al.", "2014 kim", "et al. 2015", "2015 wolfson", "wolfson et al.", "et al. 2016", "2016 saxton", "saxton et al.", "al. 2016 .", "2016 . 2", "2 castor1", "castor1 in a", "in a homodimer", "a homodimer or", "homodimer or a", "or a heterodimer", "a heterodimer with", "heterodimer with castor2", "with castor2 binds", "castor2 binds arginine", "binds arginine and", "arginine and the", "and the castor1:arginine", "the castor1:arginine complex", "castor1:arginine complex is", "complex is likewise", "is likewise released", "likewise released from", "released from gator2", "gator2 allowing", "gator2 to activate", "to activate mtorc1", "mtorc1 chantranupong", "2016 gai", "gai et al.", "2016 xia", "xia et al.", "2016 . 3", "3 bmt2", "bmt2 samtor", "a negative regulator", "negative regulator of", "regulator of mtorc1", "of mtorc1 activation", "activation binds", "binds s adenosylmethionine", "adenosylmethionine sam", "a derivative of", "derivative of methionine", "methionine gu", "gu et al.", ". the binding", "binding of sam", "of sam causes", "sam causes bmt2", "causes bmt2 to", "bmt2 to dissociate", "to dissociate from", "dissociate from gator1", "gator1 allowing", "allowing the activation", "the activation of", "activation of mtorc1.", "of mtorc1. 4", "4 the", "the amino acid", "amino acid transporter", "acid transporter slc38a9", "transporter slc38a9 binds", "slc38a9 binds arginine", "arginine and slc38a9", "and slc38a9 then", "slc38a9 then acts", "then acts as", "as a gef", "a gef to", "gef to convert", "to convert rraga", "convert rraga b:gdp", "rraga b:gdp to", "b:gdp to the", "to the active", "the active form", "form rraga", "b:gtp rebsamen", "rebsamen et al.", "2015 wang", "wang et al.", "2015 wyant", "wyant et al.", "2017 shen", "shen and sabatini", "and sabatini 2018", "sabatini 2018 .", "2018 . amino", ". amino acid", "amino acid starvation", "acid starvation also", "starvation also regulates", "also regulates the", "regulates the assembly", "the assembly of", "assembly of the", "of the v0", "the v0 and", "v0 and v1", "and v1 subunits", "v1 subunits of", "subunits of v", "of v atpase", "v atpase by", "atpase by an", "by an uncharacterized", "an uncharacterized mechanism", "mechanism stransky", "stransky and forgac", "and forgac 2015", "2015 and", "and v atpase", "v atpase is", "atpase is required", "is required for", "required for activation", "for activation of", "activation of mtorc1", "of mtorc1 by", "mtorc1 by amino", "by amino acids", "acids zoncu", "zoncu et al.", "et al. 2011", "al. 2011 .", "2011 . glutamine", ". glutamine activates", "glutamine activates mtorc1", "activates mtorc1 by", "mtorc1 by a", "by a mechanism", "a mechanism that", "mechanism that is", "that is independent", "is independent of", "independent of the", "the rag gtpases", "gtpases requires", "arf1 but", "but is not", "is not yet", "not yet fully", "yet fully elucidated", "elucidated jewell", "jewell et al.", "al. 2015 .", "the mtorc1 complex acts", "mtorc1 complex acts as", "complex acts as an", "acts as an integrator", "as an integrator that", "an integrator that regulates", "integrator that regulates translation", "regulates translation lipid", "translation lipid synthesis", "lipid synthesis autophagy", "autophagy and cell", "and cell growth in", "cell growth in response", "growth in response to", "in response to multiple", "response to multiple inputs", "multiple inputs notably", "inputs notably glucose", "notably glucose oxygen", "oxygen amino acids", "amino acids and", "acids and growth", "and growth factors such", "growth factors such as", "factors such as insulin", "as insulin reviewed", "insulin reviewed in", "reviewed in sabatini 2017", "sabatini 2017 meng", "2017 meng et", "meng et al. 2018", "al. 2018 kim", "2018 kim and", "kim and guan 2019", "and guan 2019 .
mtor", "2019 .
mtor the", ".
mtor the kinase", "the kinase subunit of", "kinase subunit of mtorc1", "of mtorc1 is", "mtorc1 is activated", "is activated by interaction", "activated by interaction with", "by interaction with rheb:gtp", "interaction with rheb:gtp at", "with rheb:gtp at the", "rheb:gtp at the cytosolic", "at the cytosolic face", "the cytosolic face of", "cytosolic face of lysosomal", "face of lysosomal membrane", "lysosomal membrane long", "membrane long et", "long et al. 2005", "al. 2005 tee", "2005 tee et", "tee et al. 2005", "al. 2005 long", "2005 long et", "long et al. 2007", "al. 2007 yang", "2007 yang et", "yang et al. 2017", "et al. 2017 .", "al. 2017 . recruitment", "2017 . recruitment of", ". recruitment of mtorc1", "recruitment of mtorc1 to", "of mtorc1 to the", "mtorc1 to the lysosomal", "to the lysosomal membrane", "the lysosomal membrane is", "lysosomal membrane is intricate", "membrane is intricate and", "is intricate and incompletely", "intricate and incompletely understood.", "and incompletely understood. at", "incompletely understood. at the", "understood. at the center", "at the center of", "the center of the", "center of the system", "of the system is", "the system is a", "system is a complex", "is a complex of", "a complex of two", "complex of two small", "of two small gtpases", "small gtpases the", "gtpases the rag", "rag heterodimer rraga", "heterodimer rraga or", "rraga or rragb bound", "or rragb bound to", "rragb bound to rragc", "bound to rragc or", "to rragc or rragd", "rragc or rragd .", "or rragd . the", "rragd . the rag", ". the rag heterodimer", "the rag heterodimer is", "rag heterodimer is tethered", "heterodimer is tethered to", "is tethered to the", "tethered to the membrane", "to the membrane by", "the membrane by the", "membrane by the ragulator", "by the ragulator complex", "ragulator complex which", "complex which also", "which also binds the", "also binds the v", "binds the v atpase", "the v atpase complex.", "v atpase complex. the", "atpase complex. the rag", "complex. the rag heterodimer", "the rag heterodimer acts", "rag heterodimer acts as", "heterodimer acts as a", "acts as a cross", "as a cross regulating", "a cross regulating switch", "regulating switch with", "switch with the", "with the binding of", "the binding of gtp", "binding of gtp by", "of gtp by one", "gtp by one subunit", "by one subunit inhibiting", "one subunit inhibiting the", "subunit inhibiting the exchange", "inhibiting the exchange of", "the exchange of gdp", "exchange of gdp for", "of gdp for gtp", "gdp for gtp by", "for gtp by the", "gtp by the other", "by the other subunit", "other subunit shen", "subunit shen et", "shen et al. 2017", "al. 2017 . the", "2017 . the active", ". the active conformation", "the active conformation of", "active conformation of the", "conformation of the rag", "of the rag heterodimer", "the rag heterodimer that", "rag heterodimer that recruits", "heterodimer that recruits mtorc1", "that recruits mtorc1 to", "recruits mtorc1 to the", "lysosomal membrane is rraga", "membrane is rraga b:gtp:rragc", "is rraga b:gtp:rragc d:gdp", "rraga b:gtp:rragc d:gdp while", "b:gtp:rragc d:gdp while the", "d:gdp while the inactive", "while the inactive conformation", "inactive conformation rraga", "conformation rraga b:gdp:rragc", "b:gdp:rragc d:gtp releases", "d:gtp releases mtorc1", "releases mtorc1 sancak", "mtorc1 sancak et", "sancak et al. 2008", "al. 2008 kim", "2008 kim et", "kim et al. 2008", "al. 2008 sancak", "2008 sancak et", "sancak et al. 2010", "al. 2010 lawrence", "2010 lawrence et", "lawrence et al. 2018", "et al. 2018 .", "al. 2018 . gtpase", "2018 . gtpase activating", ". gtpase activating proteins", "activating proteins gaps", "gaps and guanyl", "and guanyl nucleotide exchange", "guanyl nucleotide exchange factors", "exchange factors gefs", "gefs acting upon", "acting upon the rag", "upon the rag heterodimer", "the rag heterodimer thereby", "rag heterodimer thereby regulate", "heterodimer thereby regulate recruitment", "thereby regulate recruitment of", "regulate recruitment of mtorc1.", "recruitment of mtorc1. rheb:gtp", "of mtorc1. rheb:gtp at", "mtorc1. rheb:gtp at the", "rheb:gtp at the lysosomal", "at the lysosomal membrane", "the lysosomal membrane also", "lysosomal membrane also binds", "membrane also binds mtorc1", "also binds mtorc1 and", "binds mtorc1 and directly", "mtorc1 and directly activates", "and directly activates mtorc1.", "directly activates mtorc1. during", "activates mtorc1. during inactivation", "mtorc1. during inactivation of", "during inactivation of mtorc1", "inactivation of mtorc1 in", "of mtorc1 in response", "mtorc1 in response to", "in response to removal", "response to removal of", "to removal of amino", "removal of amino acids", "amino acids the", "acids the tsc", "tsc complex a", "complex a gap", "a gap for rheb", "for rheb is", "rheb is required", "is required in addition", "required in addition to", "in addition to the", "addition to the inactive", "to the inactive rag", "the inactive rag complex", "inactive rag complex to", "rag complex to release", "complex to release mtorc1", "to release mtorc1 from", "release mtorc1 from rheb", "mtorc1 from rheb and", "from rheb and hence", "rheb and hence fully", "and hence fully release", "hence fully release mtorc1", "fully release mtorc1 from", "release mtorc1 from the", "mtorc1 from the lysosomal", "from the lysosomal membrane", "lysosomal membrane demetriades", "membrane demetriades et", "demetriades et al. 2014", "et al. 2014 .
amino", "al. 2014 .
amino acids", "2014 .
amino acids regulate", ".
amino acids regulate recruitment", "acids regulate recruitment of", "regulate recruitment of mtorc1", "the lysosomal membrane by", "lysosomal membrane by at", "membrane by at least", "by at least 4", "at least 4 mechanisms", "4 mechanisms reviewed", "mechanisms reviewed in", "reviewed in zhuang et", "in zhuang et al.", "zhuang et al. 2019", "al. 2019 wolfson", "2019 wolfson and", "wolfson and sabatini 2017", "sabatini 2017 yao", "2017 yao et", "yao et al. 2017", "al. 2017 . 1", ". 1 sestrin1", "sesn1 or sestrin2", "or sestrin2 sesn2", "sesn2 binds leucine", "binds leucine and the", "leucine and the sestrin1", "and the sestrin1 2:leucine", "the sestrin1 2:leucine complex", "sestrin1 2:leucine complex is", "2:leucine complex is then", "complex is then released", "is then released from", "then released from the", "released from the gator2", "from the gator2 complex", "gator2 complex allowing", "complex allowing gator2", "allowing gator2 to positively", "gator2 to positively regulate", "to positively regulate mtorc1", "positively regulate mtorc1 activation", "mtorc1 activation chantranupong", "activation chantranupong et", "chantranupong et al. 2014", "al. 2014 parmigiani", "2014 parmigiani et", "parmigiani et al. 2014", "al. 2014 kim", "2014 kim et", "kim et al. 2015", "al. 2015 wolfson", "2015 wolfson et", "wolfson et al. 2016", "al. 2016 saxton", "2016 saxton et", "saxton et al. 2016", "et al. 2016 .", "al. 2016 . 2", ". 2 castor1", "2 castor1 in", "castor1 in a homodimer", "in a homodimer or", "a homodimer or a", "homodimer or a heterodimer", "or a heterodimer with", "a heterodimer with castor2", "heterodimer with castor2 binds", "with castor2 binds arginine", "castor2 binds arginine and", "binds arginine and the", "arginine and the castor1:arginine", "and the castor1:arginine complex", "the castor1:arginine complex is", "castor1:arginine complex is likewise", "complex is likewise released", "is likewise released from", "likewise released from gator2", "from gator2 allowing", "gator2 allowing gator2", "allowing gator2 to activate", "gator2 to activate mtorc1", "activate mtorc1 chantranupong", "mtorc1 chantranupong et", "chantranupong et al. 2016", "al. 2016 gai", "2016 gai et", "gai et al. 2016", "al. 2016 xia", "2016 xia et", "xia et al. 2016", "al. 2016 . 3", ". 3 bmt2", "samtor a", "a negative regulator of", "negative regulator of mtorc1", "regulator of mtorc1 activation", "mtorc1 activation binds", "activation binds s", "s adenosylmethionine sam", "sam a", "a derivative of methionine", "of methionine gu", "methionine gu et", "gu et al. 2017", "2017 . the binding", ". the binding of", "the binding of sam", "binding of sam causes", "of sam causes bmt2", "sam causes bmt2 to", "causes bmt2 to dissociate", "bmt2 to dissociate from", "to dissociate from gator1", "from gator1 allowing", "gator1 allowing the", "allowing the activation of", "the activation of mtorc1.", "activation of mtorc1. 4", "mtorc1. 4 the", "4 the amino", "the amino acid transporter", "amino acid transporter slc38a9", "acid transporter slc38a9 binds", "transporter slc38a9 binds arginine", "slc38a9 binds arginine and", "binds arginine and slc38a9", "arginine and slc38a9 then", "and slc38a9 then acts", "slc38a9 then acts as", "then acts as a", "acts as a gef", "as a gef to", "a gef to convert", "gef to convert rraga", "to convert rraga b:gdp", "convert rraga b:gdp to", "rraga b:gdp to the", "b:gdp to the active", "to the active form", "active form rraga", "form rraga b:gtp", "rraga b:gtp rebsamen", "b:gtp rebsamen et", "rebsamen et al. 2015", "al. 2015 wang", "2015 wang et", "wang et al. 2015", "al. 2015 wyant", "2015 wyant et", "wyant et al. 2017", "al. 2017 shen", "2017 shen and", "shen and sabatini 2018", "and sabatini 2018 .", "sabatini 2018 . amino", "2018 . amino acid", ". amino acid starvation", "amino acid starvation also", "acid starvation also regulates", "starvation also regulates the", "also regulates the assembly", "regulates the assembly of", "the assembly of the", "assembly of the v0", "of the v0 and", "the v0 and v1", "v0 and v1 subunits", "and v1 subunits of", "v1 subunits of v", "subunits of v atpase", "of v atpase by", "v atpase by an", "atpase by an uncharacterized", "by an uncharacterized mechanism", "uncharacterized mechanism stransky", "mechanism stransky and", "stransky and forgac 2015", "forgac 2015 and", "2015 and v", "and v atpase is", "v atpase is required", "atpase is required for", "is required for activation", "required for activation of", "for activation of mtorc1", "activation of mtorc1 by", "of mtorc1 by amino", "mtorc1 by amino acids", "amino acids zoncu", "acids zoncu et", "zoncu et al. 2011", "et al. 2011 .", "al. 2011 . glutamine", "2011 . glutamine activates", ". glutamine activates mtorc1", "glutamine activates mtorc1 by", "activates mtorc1 by a", "mtorc1 by a mechanism", "by a mechanism that", "a mechanism that is", "mechanism that is independent", "that is independent of", "is independent of the", "independent of the rag", "of the rag gtpases", "rag gtpases requires", "gtpases requires arf1", "requires arf1 but", "arf1 but is", "but is not yet", "is not yet fully", "not yet fully elucidated", "fully elucidated jewell", "elucidated jewell et", "jewell et al. 2015", "et al. 2015 .", "the mtorc1 complex acts as", "mtorc1 complex acts as an", "complex acts as an integrator", "acts as an integrator that", "as an integrator that regulates", "an integrator that regulates translation", "that regulates translation lipid", "regulates translation lipid synthesis", "synthesis autophagy and", "autophagy and cell growth", "and cell growth in response", "cell growth in response to", "growth in response to multiple", "in response to multiple inputs", "to multiple inputs notably", "multiple inputs notably glucose", "glucose oxygen amino", "amino acids and growth", "acids and growth factors", "and growth factors such as", "growth factors such as insulin", "such as insulin reviewed", "as insulin reviewed in", "insulin reviewed in sabatini", "in sabatini 2017 meng", "sabatini 2017 meng et", "2017 meng et al.", "et al. 2018 kim", "al. 2018 kim and", "2018 kim and guan", "kim and guan 2019 .
mtor", "guan 2019 .
mtor the", "2019 .
mtor the kinase", ".
mtor the kinase subunit", "the kinase subunit of mtorc1", "subunit of mtorc1 is", "of mtorc1 is activated", "mtorc1 is activated by", "is activated by interaction with", "activated by interaction with rheb:gtp", "by interaction with rheb:gtp at", "interaction with rheb:gtp at the", "with rheb:gtp at the cytosolic", "rheb:gtp at the cytosolic face", "at the cytosolic face of", "the cytosolic face of lysosomal", "cytosolic face of lysosomal membrane", "of lysosomal membrane long", "lysosomal membrane long et", "membrane long et al.", "et al. 2005 tee", "al. 2005 tee et", "2005 tee et al.", "et al. 2005 long", "al. 2005 long et", "2005 long et al.", "et al. 2007 yang", "al. 2007 yang et", "2007 yang et al.", "yang et al. 2017 .", "et al. 2017 . recruitment", "al. 2017 . recruitment of", "2017 . recruitment of mtorc1", ". recruitment of mtorc1 to", "recruitment of mtorc1 to the", "of mtorc1 to the lysosomal", "mtorc1 to the lysosomal membrane", "to the lysosomal membrane is", "the lysosomal membrane is intricate", "lysosomal membrane is intricate and", "membrane is intricate and incompletely", "is intricate and incompletely understood.", "intricate and incompletely understood. at", "and incompletely understood. at the", "incompletely understood. at the center", "understood. at the center of", "at the center of the", "the center of the system", "center of the system is", "of the system is a", "the system is a complex", "system is a complex of", "is a complex of two", "a complex of two small", "complex of two small gtpases", "two small gtpases the", "small gtpases the rag", "gtpases the rag heterodimer", "the rag heterodimer rraga", "rag heterodimer rraga or", "heterodimer rraga or rragb", "rraga or rragb bound to", "or rragb bound to rragc", "rragb bound to rragc or", "bound to rragc or rragd", "to rragc or rragd .", "rragc or rragd . the", "or rragd . the rag", "rragd . the rag heterodimer", ". the rag heterodimer is", "the rag heterodimer is tethered", "rag heterodimer is tethered to", "heterodimer is tethered to the", "is tethered to the membrane", "tethered to the membrane by", "to the membrane by the", "the membrane by the ragulator", "membrane by the ragulator complex", "the ragulator complex which", "ragulator complex which also", "complex which also binds", "which also binds the v", "also binds the v atpase", "binds the v atpase complex.", "the v atpase complex. the", "v atpase complex. the rag", "atpase complex. the rag heterodimer", "complex. the rag heterodimer acts", "the rag heterodimer acts as", "rag heterodimer acts as a", "heterodimer acts as a cross", "acts as a cross regulating", "as a cross regulating switch", "cross regulating switch with", "regulating switch with the", "switch with the binding", "with the binding of gtp", "the binding of gtp by", "binding of gtp by one", "of gtp by one subunit", "gtp by one subunit inhibiting", "by one subunit inhibiting the", "one subunit inhibiting the exchange", "subunit inhibiting the exchange of", "inhibiting the exchange of gdp", "the exchange of gdp for", "exchange of gdp for gtp", "of gdp for gtp by", "gdp for gtp by the", "for gtp by the other", "gtp by the other subunit", "the other subunit shen", "other subunit shen et", "subunit shen et al.", "shen et al. 2017 .", "et al. 2017 . the", "al. 2017 . the active", "2017 . the active conformation", ". the active conformation of", "the active conformation of the", "active conformation of the rag", "conformation of the rag heterodimer", "of the rag heterodimer that", "the rag heterodimer that recruits", "rag heterodimer that recruits mtorc1", "heterodimer that recruits mtorc1 to", "that recruits mtorc1 to the", "recruits mtorc1 to the lysosomal", "the lysosomal membrane is rraga", "lysosomal membrane is rraga b:gtp:rragc", "membrane is rraga b:gtp:rragc d:gdp", "is rraga b:gtp:rragc d:gdp while", "rraga b:gtp:rragc d:gdp while the", "b:gtp:rragc d:gdp while the inactive", "d:gdp while the inactive conformation", "the inactive conformation rraga", "inactive conformation rraga b:gdp:rragc", "conformation rraga b:gdp:rragc d:gtp", "rraga b:gdp:rragc d:gtp releases", "b:gdp:rragc d:gtp releases mtorc1", "releases mtorc1 sancak et", "mtorc1 sancak et al.", "et al. 2008 kim", "al. 2008 kim et", "2008 kim et al.", "et al. 2008 sancak", "al. 2008 sancak et", "2008 sancak et al.", "et al. 2010 lawrence", "al. 2010 lawrence et", "2010 lawrence et al.", "lawrence et al. 2018 .", "et al. 2018 . gtpase", "al. 2018 . gtpase activating", "2018 . gtpase activating proteins", "gtpase activating proteins gaps", "proteins gaps and", "gaps and guanyl nucleotide", "and guanyl nucleotide exchange factors", "nucleotide exchange factors gefs", "factors gefs acting", "gefs acting upon the", "acting upon the rag heterodimer", "upon the rag heterodimer thereby", "the rag heterodimer thereby regulate", "rag heterodimer thereby regulate recruitment", "heterodimer thereby regulate recruitment of", "thereby regulate recruitment of mtorc1.", "regulate recruitment of mtorc1. rheb:gtp", "recruitment of mtorc1. rheb:gtp at", "of mtorc1. rheb:gtp at the", "mtorc1. rheb:gtp at the lysosomal", "rheb:gtp at the lysosomal membrane", "at the lysosomal membrane also", "the lysosomal membrane also binds", "lysosomal membrane also binds mtorc1", "membrane also binds mtorc1 and", "also binds mtorc1 and directly", "binds mtorc1 and directly activates", "mtorc1 and directly activates mtorc1.", "and directly activates mtorc1. during", "directly activates mtorc1. during inactivation", "activates mtorc1. during inactivation of", "mtorc1. during inactivation of mtorc1", "during inactivation of mtorc1 in", "inactivation of mtorc1 in response", "of mtorc1 in response to", "mtorc1 in response to removal", "in response to removal of", "response to removal of amino", "to removal of amino acids", "of amino acids the", "amino acids the tsc", "acids the tsc complex", "the tsc complex a", "tsc complex a gap", "complex a gap for", "gap for rheb is", "for rheb is required", "rheb is required in", "is required in addition to", "required in addition to the", "in addition to the inactive", "addition to the inactive rag", "to the inactive rag complex", "the inactive rag complex to", "inactive rag complex to release", "rag complex to release mtorc1", "complex to release mtorc1 from", "to release mtorc1 from rheb", "release mtorc1 from rheb and", "mtorc1 from rheb and hence", "from rheb and hence fully", "rheb and hence fully release", "and hence fully release mtorc1", "hence fully release mtorc1 from", "fully release mtorc1 from the", "release mtorc1 from the lysosomal", "mtorc1 from the lysosomal membrane", "the lysosomal membrane demetriades", "lysosomal membrane demetriades et", "membrane demetriades et al.", "demetriades et al. 2014 .
amino", "et al. 2014 .
amino acids", "al. 2014 .
amino acids regulate", "2014 .
amino acids regulate recruitment", ".
amino acids regulate recruitment of", "acids regulate recruitment of mtorc1", "regulate recruitment of mtorc1 to", "to the lysosomal membrane by", "the lysosomal membrane by at", "lysosomal membrane by at least", "membrane by at least 4", "by at least 4 mechanisms", "least 4 mechanisms reviewed", "4 mechanisms reviewed in", "mechanisms reviewed in zhuang", "reviewed in zhuang et al.", "in zhuang et al. 2019", "et al. 2019 wolfson", "al. 2019 wolfson and", "2019 wolfson and sabatini", "and sabatini 2017 yao", "sabatini 2017 yao et", "2017 yao et al.", "yao et al. 2017 .", "et al. 2017 . 1", "2017 . 1 sestrin1", "1 sestrin1 sesn1", "sestrin1 sesn1 or", "sestrin2 sesn2 binds", "sesn2 binds leucine and", "binds leucine and the sestrin1", "leucine and the sestrin1 2:leucine", "and the sestrin1 2:leucine complex", "the sestrin1 2:leucine complex is", "sestrin1 2:leucine complex is then", "2:leucine complex is then released", "complex is then released from", "is then released from the", "then released from the gator2", "released from the gator2 complex", "the gator2 complex allowing", "gator2 complex allowing gator2", "complex allowing gator2 to", "allowing gator2 to positively regulate", "gator2 to positively regulate mtorc1", "to positively regulate mtorc1 activation", "regulate mtorc1 activation chantranupong", "mtorc1 activation chantranupong et", "activation chantranupong et al.", "et al. 2014 parmigiani", "al. 2014 parmigiani et", "2014 parmigiani et al.", "et al. 2014 kim", "al. 2014 kim et", "2014 kim et al.", "et al. 2015 wolfson", "al. 2015 wolfson et", "2015 wolfson et al.", "et al. 2016 saxton", "al. 2016 saxton et", "2016 saxton et al.", "saxton et al. 2016 .", "et al. 2016 . 2", "2016 . 2 castor1", ". 2 castor1 in", "2 castor1 in a", "castor1 in a homodimer or", "in a homodimer or a", "a homodimer or a heterodimer", "homodimer or a heterodimer with", "or a heterodimer with castor2", "a heterodimer with castor2 binds", "heterodimer with castor2 binds arginine", "with castor2 binds arginine and", "castor2 binds arginine and the", "binds arginine and the castor1:arginine", "arginine and the castor1:arginine complex", "and the castor1:arginine complex is", "the castor1:arginine complex is likewise", "castor1:arginine complex is likewise released", "complex is likewise released from", "is likewise released from gator2", "released from gator2 allowing", "from gator2 allowing gator2", "gator2 allowing gator2 to", "allowing gator2 to activate mtorc1", "to activate mtorc1 chantranupong", "activate mtorc1 chantranupong et", "mtorc1 chantranupong et al.", "et al. 2016 gai", "al. 2016 gai et", "2016 gai et al.", "et al. 2016 xia", "al. 2016 xia et", "2016 xia et al.", "xia et al. 2016 .", "et al. 2016 . 3", "2016 . 3 bmt2", "3 bmt2 samtor", "samtor a negative", "a negative regulator of mtorc1", "negative regulator of mtorc1 activation", "of mtorc1 activation binds", "mtorc1 activation binds s", "activation binds s adenosylmethionine", "binds s adenosylmethionine sam", "sam a derivative", "derivative of methionine gu", "of methionine gu et", "methionine gu et al.", "gu et al. 2017 .", "al. 2017 . the binding", "2017 . the binding of", ". the binding of sam", "the binding of sam causes", "binding of sam causes bmt2", "of sam causes bmt2 to", "sam causes bmt2 to dissociate", "causes bmt2 to dissociate from", "bmt2 to dissociate from gator1", "dissociate from gator1 allowing", "from gator1 allowing the", "gator1 allowing the activation", "allowing the activation of mtorc1.", "the activation of mtorc1. 4", "of mtorc1. 4 the", "mtorc1. 4 the amino", "4 the amino acid", "the amino acid transporter slc38a9", "amino acid transporter slc38a9 binds", "acid transporter slc38a9 binds arginine", "transporter slc38a9 binds arginine and", "slc38a9 binds arginine and slc38a9", "binds arginine and slc38a9 then", "arginine and slc38a9 then acts", "and slc38a9 then acts as", "slc38a9 then acts as a", "then acts as a gef", "acts as a gef to", "as a gef to convert", "a gef to convert rraga", "gef to convert rraga b:gdp", "to convert rraga b:gdp to", "convert rraga b:gdp to the", "rraga b:gdp to the active", "b:gdp to the active form", "the active form rraga", "active form rraga b:gtp", "rraga b:gtp rebsamen et", "b:gtp rebsamen et al.", "et al. 2015 wang", "al. 2015 wang et", "2015 wang et al.", "et al. 2015 wyant", "al. 2015 wyant et", "2015 wyant et al.", "et al. 2017 shen", "al. 2017 shen and", "2017 shen and sabatini", "shen and sabatini 2018 .", "and sabatini 2018 . amino", "sabatini 2018 . amino acid", "2018 . amino acid starvation", ". amino acid starvation also", "amino acid starvation also regulates", "acid starvation also regulates the", "starvation also regulates the assembly", "also regulates the assembly of", "regulates the assembly of the", "the assembly of the v0", "assembly of the v0 and", "of the v0 and v1", "the v0 and v1 subunits", "v0 and v1 subunits of", "and v1 subunits of v", "v1 subunits of v atpase", "subunits of v atpase by", "of v atpase by an", "v atpase by an uncharacterized", "atpase by an uncharacterized mechanism", "an uncharacterized mechanism stransky", "uncharacterized mechanism stransky and", "mechanism stransky and forgac", "and forgac 2015 and", "forgac 2015 and v", "2015 and v atpase", "and v atpase is required", "v atpase is required for", "atpase is required for activation", "is required for activation of", "required for activation of mtorc1", "for activation of mtorc1 by", "activation of mtorc1 by amino", "of mtorc1 by amino acids", "by amino acids zoncu", "amino acids zoncu et", "acids zoncu et al.", "zoncu et al. 2011 .", "et al. 2011 . glutamine", "al. 2011 . glutamine activates", "2011 . glutamine activates mtorc1", ". glutamine activates mtorc1 by", "glutamine activates mtorc1 by a", "activates mtorc1 by a mechanism", "mtorc1 by a mechanism that", "by a mechanism that is", "a mechanism that is independent", "mechanism that is independent of", "that is independent of the", "is independent of the rag", "independent of the rag gtpases", "the rag gtpases requires", "rag gtpases requires arf1", "requires arf1 but is", "arf1 but is not", "but is not yet fully", "is not yet fully elucidated", "yet fully elucidated jewell", "fully elucidated jewell et", "elucidated jewell et al.", "jewell et al. 2015 ." ] }, { "record_id": "GLY_000594_1_702", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "964975", "r hsa", "hsa 964975", "r hsa 964975" ] }, { "record_id": "GLY_000594_1_702", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "vitamin b6", "b6 activation", "activation to", "to pyridoxal", "pyridoxal phosphate", "vitamin b6 activation", "b6 activation to", "activation to pyridoxal", "to pyridoxal phosphate", "vitamin b6 activation to", "b6 activation to pyridoxal", "activation to pyridoxal phosphate", "vitamin b6 activation to pyridoxal", "b6 activation to pyridoxal phosphate", "animals cannot", "cannot synthesize", "synthesize pyridoxal", "pyridoxal 5'", "5' phosphate", "which is", "is a", "a ligand", "ligand in", "in aminotransferases", "aminotransferases and", "and other", "other enzymes.", "enzymes. plp's", "plp's accessible", "accessible derivatives", "derivatives pyridoxine", "and pyridoxamine", "pyridoxamine are", "are traditionally", "traditionally called", "called vitamins", "vitamins b6.", "b6. they", "they are", "are taken", "taken up", "up nutritionally", "nutritionally from", "from bacteria", "bacteria and", "and plants", "but also", "also created", "created from", "from plp", "plp in", "in the", "the body.", "body. the", "the pathways", "pathways used", "used to", "to recycle", "recycle plp", "plp from", "from these", "these three", "three compounds", "compounds can", "can therefore", "therefore be", "be called", "called vitamin", "activation as", "as well", "well as", "as plp", "plp salvage.", "salvage. because", "because of", "of the", "the close", "close similarity", "similarity of", "the molecules", "only two", "two enzymes", "enzymes are", "are needed", "needed for", "for the", "the task", "mccormick &", "& chen", "1999 .", "animals cannot synthesize", "cannot synthesize pyridoxal", "synthesize pyridoxal 5'", "pyridoxal 5' phosphate", "phosphate plp", "plp which", "which is a", "is a ligand", "a ligand in", "ligand in aminotransferases", "in aminotransferases and", "aminotransferases and other", "and other enzymes.", "other enzymes. plp's", "enzymes. plp's accessible", "plp's accessible derivatives", "accessible derivatives pyridoxine", "pyridoxine pyridoxal", "pyridoxal and", "and pyridoxamine are", "pyridoxamine are traditionally", "are traditionally called", "traditionally called vitamins", "called vitamins b6.", "vitamins b6. they", "b6. they are", "they are taken", "are taken up", "taken up nutritionally", "up nutritionally from", "nutritionally from bacteria", "from bacteria and", "bacteria and plants", "plants but", "but also created", "also created from", "created from plp", "from plp in", "plp in the", "in the body.", "the body. the", "body. the pathways", "the pathways used", "pathways used to", "used to recycle", "to recycle plp", "recycle plp from", "plp from these", "from these three", "these three compounds", "three compounds can", "compounds can therefore", "can therefore be", "therefore be called", "be called vitamin", "called vitamin b6", "b6 activation as", "activation as well", "as well as", "well as plp", "as plp salvage.", "plp salvage. because", "salvage. because of", "because of the", "of the close", "the close similarity", "close similarity of", "similarity of the", "of the molecules", "molecules only", "only two enzymes", "two enzymes are", "enzymes are needed", "are needed for", "needed for the", "for the task", "task mccormick", "mccormick & chen", "chen 1999", "animals cannot synthesize pyridoxal", "cannot synthesize pyridoxal 5'", "synthesize pyridoxal 5' phosphate", "5' phosphate plp", "plp which is", "which is a ligand", "is a ligand in", "a ligand in aminotransferases", "ligand in aminotransferases and", "in aminotransferases and other", "aminotransferases and other enzymes.", "and other enzymes. plp's", "other enzymes. plp's accessible", "enzymes. plp's accessible derivatives", "plp's accessible derivatives pyridoxine", "derivatives pyridoxine pyridoxal", "pyridoxal and pyridoxamine", "and pyridoxamine are traditionally", "pyridoxamine are traditionally called", "are traditionally called vitamins", "traditionally called vitamins b6.", "called vitamins b6. they", "vitamins b6. they are", "b6. they are taken", "they are taken up", "are taken up nutritionally", "taken up nutritionally from", "up nutritionally from bacteria", "nutritionally from bacteria and", "from bacteria and plants", "and plants but", "plants but also", "but also created from", "also created from plp", "created from plp in", "from plp in the", "plp in the body.", "in the body. the", "the body. the pathways", "body. the pathways used", "the pathways used to", "pathways used to recycle", "used to recycle plp", "to recycle plp from", "recycle plp from these", "plp from these three", "from these three compounds", "these three compounds can", "three compounds can therefore", "compounds can therefore be", "can therefore be called", "therefore be called vitamin", "be called vitamin b6", "called vitamin b6 activation", "vitamin b6 activation as", "b6 activation as well", "activation as well as", "as well as plp", "well as plp salvage.", "as plp salvage. because", "plp salvage. because of", "salvage. because of the", "because of the close", "of the close similarity", "the close similarity of", "close similarity of the", "similarity of the molecules", "the molecules only", "molecules only two", "only two enzymes are", "two enzymes are needed", "enzymes are needed for", "are needed for the", "needed for the task", "the task mccormick", "task mccormick &", "& chen 1999", "chen 1999 .", "animals cannot synthesize pyridoxal 5'", "cannot synthesize pyridoxal 5' phosphate", "pyridoxal 5' phosphate plp", "phosphate plp which", "plp which is a", "which is a ligand in", "is a ligand in aminotransferases", "a ligand in aminotransferases and", "ligand in aminotransferases and other", "in aminotransferases and other enzymes.", "aminotransferases and other enzymes. plp's", "and other enzymes. plp's accessible", "other enzymes. plp's accessible derivatives", "enzymes. plp's accessible derivatives pyridoxine", "accessible derivatives pyridoxine pyridoxal", "pyridoxine pyridoxal and", "pyridoxal and pyridoxamine are", "and pyridoxamine are traditionally called", "pyridoxamine are traditionally called vitamins", "are traditionally called vitamins b6.", "traditionally called vitamins b6. they", "called vitamins b6. they are", "vitamins b6. they are taken", "b6. they are taken up", "they are taken up nutritionally", "are taken up nutritionally from", "taken up nutritionally from bacteria", "up nutritionally from bacteria and", "nutritionally from bacteria and plants", "bacteria and plants but", "and plants but also", "plants but also created", "but also created from plp", "also created from plp in", "created from plp in the", "from plp in the body.", "plp in the body. the", "in the body. the pathways", "the body. the pathways used", "body. the pathways used to", "the pathways used to recycle", "pathways used to recycle plp", "used to recycle plp from", "to recycle plp from these", "recycle plp from these three", "plp from these three compounds", "from these three compounds can", "these three compounds can therefore", "three compounds can therefore be", "compounds can therefore be called", "can therefore be called vitamin", "therefore be called vitamin b6", "be called vitamin b6 activation", "called vitamin b6 activation as", "vitamin b6 activation as well", "b6 activation as well as", "activation as well as plp", "as well as plp salvage.", "well as plp salvage. because", "as plp salvage. because of", "plp salvage. because of the", "salvage. because of the close", "because of the close similarity", "of the close similarity of", "the close similarity of the", "close similarity of the molecules", "of the molecules only", "the molecules only two", "molecules only two enzymes", "only two enzymes are needed", "two enzymes are needed for", "enzymes are needed for the", "are needed for the task", "for the task mccormick", "the task mccormick &", "task mccormick & chen", "mccormick & chen 1999", "& chen 1999 ." ] }, { "record_id": "GLY_000594_1_703", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975144", "r hsa", "hsa 975144", "r hsa 975144" ] }, { "record_id": "GLY_000594_1_703", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak1 recruits", "recruits ikk", "ikk complex", "complex upon", "upon tlr7/8", "tlr7/8 or", "or 9", "9 stimulation", "irak1 recruits ikk", "recruits ikk complex", "ikk complex upon", "complex upon tlr7/8", "upon tlr7/8 or", "tlr7/8 or 9", "or 9 stimulation", "irak1 recruits ikk complex", "recruits ikk complex upon", "ikk complex upon tlr7/8", "complex upon tlr7/8 or", "upon tlr7/8 or 9", "tlr7/8 or 9 stimulation", "irak1 recruits ikk complex upon", "recruits ikk complex upon tlr7/8", "ikk complex upon tlr7/8 or", "complex upon tlr7/8 or 9", "upon tlr7/8 or 9 stimulation", "the role", "role of", "of irak1", "irak1 kinase", "kinase activity", "activity in", "in the", "the activation", "activation of", "of nf", "nf kappa", "kappa b", "b by", "by il", "il 1/tlr", "is still", "still uncertain.", "uncertain. it", "it has", "has been", "been shown", "shown that", "that a", "a kinase", "kinase dead", "dead irak1", "irak1 mutants", "mutants can", "can still", "still activate", "activate nf", "kappa b.", "b. furthermore", "stimulation of", "irak1 deficient", "deficient i1a", "i1a 293", "293 cells", "cells with", "with lmp1", "latent membrane", "membrane protein", "protein 1", "a known", "known viral", "viral activator", "activator of", "leads to", "to traf6", "traf6 polyubiquitination", "polyubiquitination and", "and ikkbeta", "ikkbeta activation", "song et", "et al", "al 2006", "2006 .", ". on", "on the", "the other", "other hand", "irak1 enhances", "enhances p65", "p65 ser536", "ser536 phosphorylation", "and p65", "p65 binding", "binding to", "to the", "the promoter", "promoter of", "b dependent", "dependent target", "target genes", "liu g", "g et", "al 2008", "2008 .

", ".

irak1", "irak1 has", "has also", "also been", "shown to", "to be", "be itself", "itself lys63", "lys63 polyubiquitinated", "probably by", "by pellino", "pellino proteins", "which have", "have e3", "e3 ligase", "ligase activity", "activity .", ". mutation", "mutation of", "of the", "the ubiquitination", "ubiquitination sites", "sites on", "on irak1", "irak1 prevented", "prevented interaction", "interaction with", "with the", "the nemo", "nemo subunit", "subunit of", "of ikk", "complex and", "and subsequent", "subsequent il", "1/tlr induced", "induced nf", "b activation", "conze et", "2008 .", ". these", "these data", "data suggest", "suggest that", "that kinase", "activity of", "irak1 is", "is not", "not essential", "essential for", "for its", "its ability", "ability to", "to activate", "while its", "its lys63", "lys63 polyubuquitination", "polyubuquitination allows", "allows irak1", "irak1 to", "to bind", "bind nemo", "nemo thus", "thus facilitating", "facilitating association", "association of", "of traf6", "traf6 and", "and tak1", "tak1 complex", "complex with", "with ikk", "complex followed", "followed by", "by induction", "induction of", "b.

upon", "

upon il", "1/tlr stimulation", "stimulation irak1", "irak1 protein", "protein can", "can undergo", "undergo covalent", "covalent modifications", "modifications including", "including phosphorylation", "kollewe et", "al 2004", "conze db", "db et", "and sumoylation", "huang et", "2004 .", ". depending", "depending upon", "upon the", "the nature", "nature of", "of its", "its modification", "irak1 may", "may perform", "perform distinct", "distinct functions", "functions including", "including activation", "of irf5/7", "uematsu et", "al 2005", "schoenemeyer et", "and stat1/3", "nguyen et", "al 2003", "2003 .", "the role of", "role of irak1", "of irak1 kinase", "irak1 kinase activity", "kinase activity in", "activity in the", "in the activation", "the activation of", "activation of nf", "of nf kappa", "nf kappa b", "kappa b by", "b by il", "by il 1/tlr", "1/tlr is", "is still uncertain.", "still uncertain. it", "uncertain. it has", "it has been", "has been shown", "been shown that", "shown that a", "that a kinase", "a kinase dead", "kinase dead irak1", "dead irak1 mutants", "irak1 mutants can", "mutants can still", "can still activate", "still activate nf", "activate nf kappa", "nf kappa b.", "kappa b. furthermore", "furthermore stimulation", "stimulation of irak1", "of irak1 deficient", "irak1 deficient i1a", "deficient i1a 293", "i1a 293 cells", "293 cells with", "cells with lmp1", "lmp1 latent", "latent membrane protein", "membrane protein 1", "1 a", "a known viral", "known viral activator", "viral activator of", "activator of nf", "b leads", "leads to traf6", "to traf6 polyubiquitination", "traf6 polyubiquitination and", "polyubiquitination and ikkbeta", "and ikkbeta activation", "activation song", "song et al", "et al 2006", "al 2006 .", "2006 . on", ". on the", "on the other", "the other hand", "hand irak1", "irak1 enhances p65", "enhances p65 ser536", "p65 ser536 phosphorylation", "phosphorylation song", "2006 and", "and p65 binding", "p65 binding to", "binding to the", "to the promoter", "the promoter of", "promoter of nf", "kappa b dependent", "b dependent target", "dependent target genes", "genes liu", "liu g et", "g et al", "et al 2008", "al 2008 .

", "2008 .

irak1", ".

irak1 has", "irak1 has also", "has also been", "also been shown", "been shown to", "shown to be", "to be itself", "be itself lys63", "itself lys63 polyubiquitinated", "polyubiquitinated probably", "probably by pellino", "by pellino proteins", "proteins which", "which have e3", "have e3 ligase", "e3 ligase activity", "ligase activity .", "activity . mutation", ". mutation of", "mutation of the", "of the ubiquitination", "the ubiquitination sites", "ubiquitination sites on", "sites on irak1", "on irak1 prevented", "irak1 prevented interaction", "prevented interaction with", "interaction with the", "with the nemo", "the nemo subunit", "nemo subunit of", "subunit of ikk", "of ikk complex", "ikk complex and", "complex and subsequent", "and subsequent il", "subsequent il 1/tlr", "il 1/tlr induced", "1/tlr induced nf", "induced nf kappa", "kappa b activation", "activation conze", "conze et al", "al 2008 .", "2008 . these", ". these data", "these data suggest", "data suggest that", "suggest that kinase", "that kinase activity", "kinase activity of", "activity of irak1", "of irak1 is", "irak1 is not", "is not essential", "not essential for", "essential for its", "for its ability", "its ability to", "ability to activate", "to activate nf", "b while", "while its lys63", "its lys63 polyubuquitination", "lys63 polyubuquitination allows", "polyubuquitination allows irak1", "allows irak1 to", "irak1 to bind", "to bind nemo", "bind nemo thus", "nemo thus facilitating", "thus facilitating association", "facilitating association of", "association of traf6", "of traf6 and", "traf6 and tak1", "and tak1 complex", "tak1 complex with", "complex with ikk", "with ikk complex", "ikk complex followed", "complex followed by", "followed by induction", "by induction of", "induction of nf", "kappa b.

upon", "b.

upon il", "

upon il 1/tlr", "il 1/tlr stimulation", "1/tlr stimulation irak1", "stimulation irak1 protein", "irak1 protein can", "protein can undergo", "can undergo covalent", "undergo covalent modifications", "covalent modifications including", "modifications including phosphorylation", "phosphorylation kollewe", "kollewe et al", "et al 2004", "ubiquitination conze", "conze db et", "db et al", "2008 and", "sumoylation huang", "huang et al", "al 2004 .", "2004 . depending", ". depending upon", "depending upon the", "upon the nature", "the nature of", "nature of its", "of its modification", "modification irak1", "irak1 may perform", "may perform distinct", "perform distinct functions", "distinct functions including", "functions including activation", "including activation of", "activation of irf5/7", "irf5/7 uematsu", "uematsu et al", "et al 2005", "2005 schoenemeyer", "schoenemeyer et al", "b song", "stat1/3 huang", "2004 nguyen", "nguyen et al", "et al 2003", "al 2003 .", "the role of irak1", "role of irak1 kinase", "of irak1 kinase activity", "irak1 kinase activity in", "kinase activity in the", "activity in the activation", "in the activation of", "the activation of nf", "activation of nf kappa", "of nf kappa b", "nf kappa b by", "kappa b by il", "b by il 1/tlr", "il 1/tlr is", "1/tlr is still", "is still uncertain. it", "still uncertain. it has", "uncertain. it has been", "it has been shown", "has been shown that", "been shown that a", "shown that a kinase", "that a kinase dead", "a kinase dead irak1", "kinase dead irak1 mutants", "dead irak1 mutants can", "irak1 mutants can still", "mutants can still activate", "can still activate nf", "still activate nf kappa", "activate nf kappa b.", "nf kappa b. furthermore", "b. furthermore stimulation", "furthermore stimulation of", "stimulation of irak1 deficient", "of irak1 deficient i1a", "irak1 deficient i1a 293", "deficient i1a 293 cells", "i1a 293 cells with", "293 cells with lmp1", "with lmp1 latent", "lmp1 latent membrane", "latent membrane protein 1", "protein 1 a", "1 a known", "a known viral activator", "known viral activator of", "viral activator of nf", "activator of nf kappa", "kappa b leads", "b leads to", "leads to traf6 polyubiquitination", "to traf6 polyubiquitination and", "traf6 polyubiquitination and ikkbeta", "polyubiquitination and ikkbeta activation", "ikkbeta activation song", "activation song et", "song et al 2006", "et al 2006 .", "al 2006 . on", "2006 . on the", ". on the other", "on the other hand", "other hand irak1", "hand irak1 enhances", "irak1 enhances p65 ser536", "enhances p65 ser536 phosphorylation", "ser536 phosphorylation song", "phosphorylation song et", "al 2006 and", "2006 and p65", "and p65 binding to", "p65 binding to the", "binding to the promoter", "to the promoter of", "the promoter of nf", "promoter of nf kappa", "nf kappa b dependent", "kappa b dependent target", "b dependent target genes", "target genes liu", "genes liu g", "liu g et al", "g et al 2008", "et al 2008 .

", "al 2008 .

irak1", "2008 .

irak1 has", ".

irak1 has also", "irak1 has also been", "has also been shown", "also been shown to", "been shown to be", "shown to be itself", "to be itself lys63", "be itself lys63 polyubiquitinated", "lys63 polyubiquitinated probably", "polyubiquitinated probably by", "probably by pellino proteins", "pellino proteins which", "proteins which have", "which have e3 ligase", "have e3 ligase activity", "e3 ligase activity .", "ligase activity . mutation", "activity . mutation of", ". mutation of the", "mutation of the ubiquitination", "of the ubiquitination sites", "the ubiquitination sites on", "ubiquitination sites on irak1", "sites on irak1 prevented", "on irak1 prevented interaction", "irak1 prevented interaction with", "prevented interaction with the", "interaction with the nemo", "with the nemo subunit", "the nemo subunit of", "nemo subunit of ikk", "subunit of ikk complex", "of ikk complex and", "ikk complex and subsequent", "complex and subsequent il", "and subsequent il 1/tlr", "subsequent il 1/tlr induced", "il 1/tlr induced nf", "1/tlr induced nf kappa", "induced nf kappa b", "nf kappa b activation", "b activation conze", "activation conze et", "conze et al 2008", "et al 2008 .", "al 2008 . these", "2008 . these data", ". these data suggest", "these data suggest that", "data suggest that kinase", "suggest that kinase activity", "that kinase activity of", "kinase activity of irak1", "activity of irak1 is", "of irak1 is not", "irak1 is not essential", "is not essential for", "not essential for its", "essential for its ability", "for its ability to", "its ability to activate", "ability to activate nf", "to activate nf kappa", "activate nf kappa b", "kappa b while", "b while its", "while its lys63 polyubuquitination", "its lys63 polyubuquitination allows", "lys63 polyubuquitination allows irak1", "polyubuquitination allows irak1 to", "allows irak1 to bind", "irak1 to bind nemo", "to bind nemo thus", "bind nemo thus facilitating", "nemo thus facilitating association", "thus facilitating association of", "facilitating association of traf6", "association of traf6 and", "of traf6 and tak1", "traf6 and tak1 complex", "and tak1 complex with", "tak1 complex with ikk", "complex with ikk complex", "with ikk complex followed", "ikk complex followed by", "complex followed by induction", "followed by induction of", "by induction of nf", "induction of nf kappa", "of nf kappa b.", "nf kappa b.

upon", "kappa b.

upon il", "b.

upon il 1/tlr", "

upon il 1/tlr stimulation", "il 1/tlr stimulation irak1", "1/tlr stimulation irak1 protein", "stimulation irak1 protein can", "irak1 protein can undergo", "protein can undergo covalent", "can undergo covalent modifications", "undergo covalent modifications including", "covalent modifications including phosphorylation", "including phosphorylation kollewe", "phosphorylation kollewe et", "kollewe et al 2004", "2004 ubiquitination", "ubiquitination conze db", "conze db et al", "db et al 2008", "al 2008 and", "2008 and sumoylation", "and sumoylation huang", "sumoylation huang et", "huang et al 2004", "et al 2004 .", "al 2004 . depending", "2004 . depending upon", ". depending upon the", "depending upon the nature", "upon the nature of", "the nature of its", "nature of its modification", "its modification irak1", "modification irak1 may", "irak1 may perform distinct", "may perform distinct functions", "perform distinct functions including", "distinct functions including activation", "functions including activation of", "including activation of irf5/7", "of irf5/7 uematsu", "irf5/7 uematsu et", "uematsu et al 2005", "al 2005 schoenemeyer", "2005 schoenemeyer et", "schoenemeyer et al 2005", "2005 nf", "kappa b song", "b song et", "and stat1/3 huang", "stat1/3 huang et", "al 2004 nguyen", "2004 nguyen et", "nguyen et al 2003", "et al 2003 .", "the role of irak1 kinase", "role of irak1 kinase activity", "of irak1 kinase activity in", "irak1 kinase activity in the", "kinase activity in the activation", "activity in the activation of", "in the activation of nf", "the activation of nf kappa", "activation of nf kappa b", "of nf kappa b by", "nf kappa b by il", "kappa b by il 1/tlr", "by il 1/tlr is", "il 1/tlr is still", "1/tlr is still uncertain.", "is still uncertain. it has", "still uncertain. it has been", "uncertain. it has been shown", "it has been shown that", "has been shown that a", "been shown that a kinase", "shown that a kinase dead", "that a kinase dead irak1", "a kinase dead irak1 mutants", "kinase dead irak1 mutants can", "dead irak1 mutants can still", "irak1 mutants can still activate", "mutants can still activate nf", "can still activate nf kappa", "still activate nf kappa b.", "activate nf kappa b. furthermore", "kappa b. furthermore stimulation", "b. furthermore stimulation of", "furthermore stimulation of irak1", "stimulation of irak1 deficient i1a", "of irak1 deficient i1a 293", "irak1 deficient i1a 293 cells", "deficient i1a 293 cells with", "i1a 293 cells with lmp1", "cells with lmp1 latent", "with lmp1 latent membrane", "lmp1 latent membrane protein", "membrane protein 1 a", "protein 1 a known", "1 a known viral", "a known viral activator of", "known viral activator of nf", "viral activator of nf kappa", "activator of nf kappa b", "nf kappa b leads", "kappa b leads to", "b leads to traf6", "leads to traf6 polyubiquitination and", "to traf6 polyubiquitination and ikkbeta", "traf6 polyubiquitination and ikkbeta activation", "and ikkbeta activation song", "ikkbeta activation song et", "activation song et al", "song et al 2006 .", "et al 2006 . on", "al 2006 . on the", "2006 . on the other", ". on the other hand", "the other hand irak1", "other hand irak1 enhances", "hand irak1 enhances p65", "irak1 enhances p65 ser536 phosphorylation", "p65 ser536 phosphorylation song", "ser536 phosphorylation song et", "phosphorylation song et al", "et al 2006 and", "al 2006 and p65", "2006 and p65 binding", "and p65 binding to the", "p65 binding to the promoter", "binding to the promoter of", "to the promoter of nf", "the promoter of nf kappa", "promoter of nf kappa b", "of nf kappa b dependent", "nf kappa b dependent target", "kappa b dependent target genes", "dependent target genes liu", "target genes liu g", "genes liu g et", "liu g et al 2008", "g et al 2008 .

", "et al 2008 .

irak1", "al 2008 .

irak1 has", "2008 .

irak1 has also", ".

irak1 has also been", "irak1 has also been shown", "has also been shown to", "also been shown to be", "been shown to be itself", "shown to be itself lys63", "to be itself lys63 polyubiquitinated", "itself lys63 polyubiquitinated probably", "lys63 polyubiquitinated probably by", "polyubiquitinated probably by pellino", "by pellino proteins which", "pellino proteins which have", "proteins which have e3", "which have e3 ligase activity", "have e3 ligase activity .", "e3 ligase activity . mutation", "ligase activity . mutation of", "activity . mutation of the", ". mutation of the ubiquitination", "mutation of the ubiquitination sites", "of the ubiquitination sites on", "the ubiquitination sites on irak1", "ubiquitination sites on irak1 prevented", "sites on irak1 prevented interaction", "on irak1 prevented interaction with", "irak1 prevented interaction with the", "prevented interaction with the nemo", "interaction with the nemo subunit", "with the nemo subunit of", "the nemo subunit of ikk", "nemo subunit of ikk complex", "subunit of ikk complex and", "of ikk complex and subsequent", "ikk complex and subsequent il", "complex and subsequent il 1/tlr", "and subsequent il 1/tlr induced", "subsequent il 1/tlr induced nf", "il 1/tlr induced nf kappa", "1/tlr induced nf kappa b", "induced nf kappa b activation", "kappa b activation conze", "b activation conze et", "activation conze et al", "conze et al 2008 .", "et al 2008 . these", "al 2008 . these data", "2008 . these data suggest", ". these data suggest that", "these data suggest that kinase", "data suggest that kinase activity", "suggest that kinase activity of", "that kinase activity of irak1", "kinase activity of irak1 is", "activity of irak1 is not", "of irak1 is not essential", "irak1 is not essential for", "is not essential for its", "not essential for its ability", "essential for its ability to", "for its ability to activate", "its ability to activate nf", "ability to activate nf kappa", "to activate nf kappa b", "nf kappa b while", "kappa b while its", "b while its lys63", "while its lys63 polyubuquitination allows", "its lys63 polyubuquitination allows irak1", "lys63 polyubuquitination allows irak1 to", "polyubuquitination allows irak1 to bind", "allows irak1 to bind nemo", "irak1 to bind nemo thus", "to bind nemo thus facilitating", "bind nemo thus facilitating association", "nemo thus facilitating association of", "thus facilitating association of traf6", "facilitating association of traf6 and", "association of traf6 and tak1", "of traf6 and tak1 complex", "traf6 and tak1 complex with", "and tak1 complex with ikk", "tak1 complex with ikk complex", "complex with ikk complex followed", "with ikk complex followed by", "ikk complex followed by induction", "complex followed by induction of", "followed by induction of nf", "by induction of nf kappa", "induction of nf kappa b.", "of nf kappa b.

upon", "nf kappa b.

upon il", "kappa b.

upon il 1/tlr", "b.

upon il 1/tlr stimulation", "

upon il 1/tlr stimulation irak1", "il 1/tlr stimulation irak1 protein", "1/tlr stimulation irak1 protein can", "stimulation irak1 protein can undergo", "irak1 protein can undergo covalent", "protein can undergo covalent modifications", "can undergo covalent modifications including", "undergo covalent modifications including phosphorylation", "modifications including phosphorylation kollewe", "including phosphorylation kollewe et", "phosphorylation kollewe et al", "al 2004 ubiquitination", "ubiquitination conze db et", "conze db et al 2008", "et al 2008 and", "al 2008 and sumoylation", "and sumoylation huang et", "sumoylation huang et al", "huang et al 2004 .", "et al 2004 . depending", "al 2004 . depending upon", "2004 . depending upon the", ". depending upon the nature", "depending upon the nature of", "upon the nature of its", "the nature of its modification", "of its modification irak1", "its modification irak1 may", "modification irak1 may perform", "irak1 may perform distinct functions", "may perform distinct functions including", "perform distinct functions including activation", "distinct functions including activation of", "functions including activation of irf5/7", "activation of irf5/7 uematsu", "of irf5/7 uematsu et", "irf5/7 uematsu et al", "et al 2005 schoenemeyer", "al 2005 schoenemeyer et", "2005 schoenemeyer et al", "al 2005 nf", "2005 nf kappa", "nf kappa b song", "kappa b song et", "b song et al", "2006 and stat1/3", "and stat1/3 huang et", "stat1/3 huang et al", "et al 2004 nguyen", "al 2004 nguyen et", "2004 nguyen et al", "nguyen et al 2003 ." ] }, { "record_id": "GLY_000594_1_704", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975163", "r hsa", "hsa 975163", "r hsa 975163" ] }, { "record_id": "GLY_000594_1_704", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak2 mediated", "mediated activation", "activation of", "of tak1", "tak1 complex", "complex upon", "upon tlr7/8", "tlr7/8 or", "or 9", "9 stimulation", "irak2 mediated activation", "mediated activation of", "activation of tak1", "of tak1 complex", "tak1 complex upon", "complex upon tlr7/8", "upon tlr7/8 or", "tlr7/8 or 9", "or 9 stimulation", "irak2 mediated activation of", "mediated activation of tak1", "activation of tak1 complex", "of tak1 complex upon", "tak1 complex upon tlr7/8", "complex upon tlr7/8 or", "upon tlr7/8 or 9", "tlr7/8 or 9 stimulation", "irak2 mediated activation of tak1", "mediated activation of tak1 complex", "activation of tak1 complex upon", "of tak1 complex upon tlr7/8", "tak1 complex upon tlr7/8 or", "complex upon tlr7/8 or 9", "upon tlr7/8 or 9 stimulation", "although irak", "irak 1", "1 was", "was originally", "originally thought", "thought to", "to be", "be a", "a key", "key mediator", "mediator of", "of traf6", "traf6 activation", "activation in", "in the", "the il1r/tlr", "il1r/tlr signaling", "dong w", "w et", "et al.", "al. 2006", "recent studies", "studies showed", "showed that", "that irak", "irak 2", "but not", "not irak", "led to", "to traf6", "traf6 polyubiquitination", "keating se", "se et", "et al", "al 2007", "2007 .", ". irak", "2 loss", "loss of", "of function", "function mutants", "with mutated", "mutated traf6", "traf6 binding", "binding motifs", "could no", "no longer", "longer activate", "activate nf", "nf kb", "kb and", "and could", "longer stimulate", "stimulate traf", "traf 6", "6 ubiquitination", ". furthermore", "the proxyvirus", "proxyvirus protein", "protein a52", "an inhibitor", "inhibitor of", "of all", "all il", "il 1r/tlr", "1r/tlr pathways", "pathways to", "to nf", "kb activation", "was found", "found to", "to interact", "interact with", "with both", "both irak", "2 and", "and traf6", "irak 1.", "1. further", "further work", "work showed", "that a52", "a52 inhibits", "inhibits irak", "2 functions", "whereas association", "association with", "with traf6", "traf6 results", "results in", "in a52", "a52 induced", "induced mapk", "mapk activation.", "activation. the", "the strong", "strong inhibition", "inhibition effect", "effect of", "of a52", "a52 was", "was also", "also observed", "observed on", "on the", "the tlr3", "tlr3 nfkb", "nfkb axis", "axis and", "and this", "this observation", "observation led", "to the", "the discovery", "discovery that", "2 is", "is recruited", "recruited to", "to tlr3", "tlr3 to", "to activate", ". thus", "a52 possibly", "possibly inhibits", "inhibits myd88", "myd88 independent", "independent tlr3", "tlr3 pathways", "via targeting", "targeting irak", "2 as", "as it", "it does", "does for", "for other", "other il", "although it", "it remains", "remains unclear", "unclear how", "how irak", "is involved", "involved in", "in tlr3", "tlr3 signaling.

irak", "signaling.

irak 2", "2 was", "was shown", "shown to", "to have", "have two", "two traf6", "motifs that", "that are", "are responsible", "responsible for", "for initiating", "initiating traf6", "traf6 signaling", "signaling transduction", "ye h", "h et", "al 2002", "2002 .", "although irak 1", "irak 1 was", "1 was originally", "was originally thought", "originally thought to", "thought to be", "to be a", "be a key", "a key mediator", "key mediator of", "mediator of traf6", "of traf6 activation", "traf6 activation in", "activation in the", "in the il1r/tlr", "the il1r/tlr signaling", "signaling dong", "dong w et", "w et al.", "et al. 2006", "recent studies showed", "studies showed that", "showed that irak", "that irak 2", "2 but", "but not irak", "not irak 1", "1 led", "led to traf6", "to traf6 polyubiquitination", "polyubiquitination keating", "keating se et", "se et al", "et al 2007", "al 2007 .", "2007 . irak", ". irak 2", "irak 2 loss", "2 loss of", "loss of function", "of function mutants", "mutants with", "with mutated traf6", "mutated traf6 binding", "traf6 binding motifs", "motifs could", "could no longer", "no longer activate", "longer activate nf", "activate nf kb", "nf kb and", "kb and could", "and could no", "no longer stimulate", "longer stimulate traf", "stimulate traf 6", "traf 6 ubiquitination", "ubiquitination keating", "2007 . furthermore", "furthermore the", "the proxyvirus protein", "proxyvirus protein a52", "an inhibitor of", "inhibitor of all", "of all il", "all il 1r/tlr", "il 1r/tlr pathways", "1r/tlr pathways to", "pathways to nf", "to nf kb", "nf kb activation", "activation was", "was found to", "found to interact", "to interact with", "interact with both", "with both irak", "both irak 2", "irak 2 and", "2 and traf6", "traf6 but", "not irak 1.", "irak 1. further", "1. further work", "further work showed", "work showed that", "showed that a52", "that a52 inhibits", "a52 inhibits irak", "inhibits irak 2", "irak 2 functions", "functions whereas", "whereas association with", "association with traf6", "with traf6 results", "traf6 results in", "results in a52", "in a52 induced", "a52 induced mapk", "induced mapk activation.", "mapk activation. the", "activation. the strong", "the strong inhibition", "strong inhibition effect", "inhibition effect of", "effect of a52", "of a52 was", "a52 was also", "was also observed", "also observed on", "observed on the", "on the tlr3", "the tlr3 nfkb", "tlr3 nfkb axis", "nfkb axis and", "axis and this", "and this observation", "this observation led", "observation led to", "led to the", "to the discovery", "the discovery that", "discovery that irak", "irak 2 is", "2 is recruited", "is recruited to", "recruited to tlr3", "to tlr3 to", "tlr3 to activate", "to activate nf", "kb keating", "2007 . thus", "thus a52", "a52 possibly inhibits", "possibly inhibits myd88", "inhibits myd88 independent", "myd88 independent tlr3", "independent tlr3 pathways", "tlr3 pathways to", "kb via", "via targeting irak", "targeting irak 2", "irak 2 as", "2 as it", "as it does", "it does for", "does for other", "for other il", "other il 1r/tlr", "pathways although", "although it remains", "it remains unclear", "remains unclear how", "unclear how irak", "how irak 2", "2 is involved", "is involved in", "involved in tlr3", "in tlr3 signaling.

irak", "tlr3 signaling.

irak 2", "signaling.

irak 2 was", "2 was shown", "was shown to", "shown to have", "to have two", "have two traf6", "two traf6 binding", "binding motifs that", "motifs that are", "that are responsible", "are responsible for", "responsible for initiating", "for initiating traf6", "initiating traf6 signaling", "traf6 signaling transduction", "transduction ye", "ye h et", "h et al", "et al 2002", "al 2002 .", "although irak 1 was", "irak 1 was originally", "1 was originally thought", "was originally thought to", "originally thought to be", "thought to be a", "to be a key", "be a key mediator", "a key mediator of", "key mediator of traf6", "mediator of traf6 activation", "of traf6 activation in", "traf6 activation in the", "activation in the il1r/tlr", "in the il1r/tlr signaling", "il1r/tlr signaling dong", "signaling dong w", "dong w et al.", "w et al. 2006", "2006 recent", "recent studies showed that", "studies showed that irak", "showed that irak 2", "irak 2 but", "2 but not", "but not irak 1", "irak 1 led", "1 led to", "led to traf6 polyubiquitination", "traf6 polyubiquitination keating", "polyubiquitination keating se", "keating se et al", "se et al 2007", "et al 2007 .", "al 2007 . irak", "2007 . irak 2", ". irak 2 loss", "irak 2 loss of", "2 loss of function", "loss of function mutants", "function mutants with", "mutants with mutated", "with mutated traf6 binding", "mutated traf6 binding motifs", "binding motifs could", "motifs could no", "could no longer activate", "no longer activate nf", "longer activate nf kb", "activate nf kb and", "nf kb and could", "kb and could no", "and could no longer", "could no longer stimulate", "no longer stimulate traf", "longer stimulate traf 6", "stimulate traf 6 ubiquitination", "6 ubiquitination keating", "ubiquitination keating se", "al 2007 . furthermore", ". furthermore the", "furthermore the proxyvirus", "the proxyvirus protein a52", "a52 an", "an inhibitor of all", "inhibitor of all il", "of all il 1r/tlr", "all il 1r/tlr pathways", "il 1r/tlr pathways to", "1r/tlr pathways to nf", "pathways to nf kb", "to nf kb activation", "kb activation was", "activation was found", "was found to interact", "found to interact with", "to interact with both", "interact with both irak", "with both irak 2", "both irak 2 and", "irak 2 and traf6", "and traf6 but", "traf6 but not", "but not irak 1.", "not irak 1. further", "irak 1. further work", "1. further work showed", "further work showed that", "work showed that a52", "showed that a52 inhibits", "that a52 inhibits irak", "a52 inhibits irak 2", "inhibits irak 2 functions", "2 functions whereas", "functions whereas association", "whereas association with traf6", "association with traf6 results", "with traf6 results in", "traf6 results in a52", "results in a52 induced", "in a52 induced mapk", "a52 induced mapk activation.", "induced mapk activation. the", "mapk activation. the strong", "activation. the strong inhibition", "the strong inhibition effect", "strong inhibition effect of", "inhibition effect of a52", "effect of a52 was", "of a52 was also", "a52 was also observed", "was also observed on", "also observed on the", "observed on the tlr3", "on the tlr3 nfkb", "the tlr3 nfkb axis", "tlr3 nfkb axis and", "nfkb axis and this", "axis and this observation", "and this observation led", "this observation led to", "observation led to the", "led to the discovery", "to the discovery that", "the discovery that irak", "discovery that irak 2", "that irak 2 is", "irak 2 is recruited", "2 is recruited to", "is recruited to tlr3", "recruited to tlr3 to", "to tlr3 to activate", "tlr3 to activate nf", "to activate nf kb", "nf kb keating", "kb keating se", "al 2007 . thus", ". thus a52", "thus a52 possibly", "a52 possibly inhibits myd88", "possibly inhibits myd88 independent", "inhibits myd88 independent tlr3", "myd88 independent tlr3 pathways", "independent tlr3 pathways to", "tlr3 pathways to nf", "nf kb via", "kb via targeting", "via targeting irak 2", "targeting irak 2 as", "irak 2 as it", "2 as it does", "as it does for", "it does for other", "does for other il", "for other il 1r/tlr", "other il 1r/tlr pathways", "1r/tlr pathways although", "pathways although it", "although it remains unclear", "it remains unclear how", "remains unclear how irak", "unclear how irak 2", "how irak 2 is", "irak 2 is involved", "2 is involved in", "is involved in tlr3", "involved in tlr3 signaling.

irak", "in tlr3 signaling.

irak 2", "tlr3 signaling.

irak 2 was", "signaling.

irak 2 was shown", "2 was shown to", "was shown to have", "shown to have two", "to have two traf6", "have two traf6 binding", "two traf6 binding motifs", "traf6 binding motifs that", "binding motifs that are", "motifs that are responsible", "that are responsible for", "are responsible for initiating", "responsible for initiating traf6", "for initiating traf6 signaling", "initiating traf6 signaling transduction", "signaling transduction ye", "transduction ye h", "ye h et al", "h et al 2002", "et al 2002 .", "although irak 1 was originally", "irak 1 was originally thought", "1 was originally thought to", "was originally thought to be", "originally thought to be a", "thought to be a key", "to be a key mediator", "be a key mediator of", "a key mediator of traf6", "key mediator of traf6 activation", "mediator of traf6 activation in", "of traf6 activation in the", "traf6 activation in the il1r/tlr", "activation in the il1r/tlr signaling", "the il1r/tlr signaling dong", "il1r/tlr signaling dong w", "signaling dong w et", "dong w et al. 2006", "al. 2006 recent", "2006 recent studies", "recent studies showed that irak", "studies showed that irak 2", "that irak 2 but", "irak 2 but not", "2 but not irak", "not irak 1 led", "irak 1 led to", "1 led to traf6", "to traf6 polyubiquitination keating", "traf6 polyubiquitination keating se", "polyubiquitination keating se et", "keating se et al 2007", "se et al 2007 .", "et al 2007 . irak", "al 2007 . irak 2", "2007 . irak 2 loss", ". irak 2 loss of", "irak 2 loss of function", "2 loss of function mutants", "of function mutants with", "function mutants with mutated", "mutants with mutated traf6", "with mutated traf6 binding motifs", "traf6 binding motifs could", "binding motifs could no", "motifs could no longer", "could no longer activate nf", "no longer activate nf kb", "longer activate nf kb and", "activate nf kb and could", "nf kb and could no", "kb and could no longer", "and could no longer stimulate", "could no longer stimulate traf", "no longer stimulate traf 6", "longer stimulate traf 6 ubiquitination", "traf 6 ubiquitination keating", "6 ubiquitination keating se", "ubiquitination keating se et", "et al 2007 . furthermore", "2007 . furthermore the", ". furthermore the proxyvirus", "furthermore the proxyvirus protein", "protein a52 an", "a52 an inhibitor", "an inhibitor of all il", "inhibitor of all il 1r/tlr", "of all il 1r/tlr pathways", "all il 1r/tlr pathways to", "il 1r/tlr pathways to nf", "1r/tlr pathways to nf kb", "pathways to nf kb activation", "nf kb activation was", "kb activation was found", "activation was found to", "was found to interact with", "found to interact with both", "to interact with both irak", "interact with both irak 2", "with both irak 2 and", "both irak 2 and traf6", "2 and traf6 but", "and traf6 but not", "traf6 but not irak", "but not irak 1. further", "not irak 1. further work", "irak 1. further work showed", "1. further work showed that", "further work showed that a52", "work showed that a52 inhibits", "showed that a52 inhibits irak", "that a52 inhibits irak 2", "a52 inhibits irak 2 functions", "irak 2 functions whereas", "2 functions whereas association", "functions whereas association with", "whereas association with traf6 results", "association with traf6 results in", "with traf6 results in a52", "traf6 results in a52 induced", "results in a52 induced mapk", "in a52 induced mapk activation.", "a52 induced mapk activation. the", "induced mapk activation. the strong", "mapk activation. the strong inhibition", "activation. the strong inhibition effect", "the strong inhibition effect of", "strong inhibition effect of a52", "inhibition effect of a52 was", "effect of a52 was also", "of a52 was also observed", "a52 was also observed on", "was also observed on the", "also observed on the tlr3", "observed on the tlr3 nfkb", "on the tlr3 nfkb axis", "the tlr3 nfkb axis and", "tlr3 nfkb axis and this", "nfkb axis and this observation", "axis and this observation led", "and this observation led to", "this observation led to the", "observation led to the discovery", "led to the discovery that", "to the discovery that irak", "the discovery that irak 2", "discovery that irak 2 is", "that irak 2 is recruited", "irak 2 is recruited to", "2 is recruited to tlr3", "is recruited to tlr3 to", "recruited to tlr3 to activate", "to tlr3 to activate nf", "tlr3 to activate nf kb", "activate nf kb keating", "nf kb keating se", "kb keating se et", "et al 2007 . thus", "2007 . thus a52", ". thus a52 possibly", "thus a52 possibly inhibits", "a52 possibly inhibits myd88 independent", "possibly inhibits myd88 independent tlr3", "inhibits myd88 independent tlr3 pathways", "myd88 independent tlr3 pathways to", "independent tlr3 pathways to nf", "tlr3 pathways to nf kb", "to nf kb via", "nf kb via targeting", "kb via targeting irak", "via targeting irak 2 as", "targeting irak 2 as it", "irak 2 as it does", "2 as it does for", "as it does for other", "it does for other il", "does for other il 1r/tlr", "for other il 1r/tlr pathways", "il 1r/tlr pathways although", "1r/tlr pathways although it", "pathways although it remains", "although it remains unclear how", "it remains unclear how irak", "remains unclear how irak 2", "unclear how irak 2 is", "how irak 2 is involved", "irak 2 is involved in", "2 is involved in tlr3", "is involved in tlr3 signaling.

irak", "involved in tlr3 signaling.

irak 2", "in tlr3 signaling.

irak 2 was", "tlr3 signaling.

irak 2 was shown", "signaling.

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", "enhance nmd.
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", "to enhance nmd.
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upf1", "triggering nmd.
upf1 is believed", "nmd.
upf1 is believed to", "is believed to form", "believed to form a", "to form a complex", "form a complex containing", "a complex containing smg1", "containing smg1 smg8", "smg8 and smg9.", "and smg9. in the", "smg9. in the key", "in the key regulatory", "the key regulatory step", "key regulatory step of", "regulatory step of nmd", "step of nmd smg1", "of nmd smg1 phosphorylates", "nmd smg1 phosphorylates upf1.", "smg1 phosphorylates upf1. the", "phosphorylates upf1. the phosphorylated", "upf1. the phosphorylated upf1", "the phosphorylated upf1 then", "phosphorylated upf1 then recruits", "upf1 then recruits either", "then recruits either smg6", "recruits either smg6 or", "either smg6 or smg5", "smg6 or smg5 and", "or smg5 and smg7.", "smg5 and smg7. smg6", "and smg7. smg6 is", "smg7. smg6 is itself", "smg6 is itself an", "is itself an endoribonuclease", "itself an endoribonuclease that", "an endoribonuclease that cleaves", "endoribonuclease that cleaves the", "that cleaves the mrna.", "cleaves the mrna. smg5", "the mrna. smg5 and", "mrna. smg5 and smg7", "smg5 and smg7 do", "and smg7 do not", "smg7 do not have", "do not have endoribonuclease", "not have endoribonuclease activty", "endoribonuclease activty but", "activty but are", "but are thought to", "are thought to recruit", "thought to recruit ribonucleases.", "to recruit ribonucleases. nonsense", "recruit ribonucleases. nonsense mediated", "ribonucleases. nonsense mediated decay", "nonsense mediated decay has", "mediated decay has been", "decay has been observed", "has been observed to", "been observed to involve", "observed to involve deadenlyation", "involve deadenlyation decapping", "decapping and both", "and both 5' to", "both 5' to 3'", "5' to 3' and", "to 3' and 3'", "3' and 3' to", "and 3' to 5'", "3' to 5' exonuclease", "to 5' exonuclease activities", "exonuclease activities but", "activities but the", "but the exact degradative", "the exact degradative pathways", "exact degradative pathways taken", "degradative pathways taken by", "pathways taken by a", "taken by a given", "by a given mrna", "a given mrna are", "given mrna are not", "mrna are not yet", "are not yet known.
upf1", "not yet known.
upf1 also", "yet known.
upf1 also plays", "known.
upf1 also plays roles", "also plays roles in", "plays roles in staufen", "roles in staufen mediated", "in staufen mediated decay", "mediated decay histone", "decay histone mrna", "mrna decay telomere", "decay telomere maintenance", "telomere maintenance genome", "maintenance genome integrity", "genome integrity and", "integrity and may", "and may play a", "may play a role", "play a role in", "a role in normal", "role in normal termination", "in normal termination of", "normal termination of translation.", "during normal translation termination erf3", "normal translation termination erf3 associates", "translation termination erf3 associates with", "termination erf3 associates with the", "erf3 associates with the ribosome", "associates with the ribosome and", "with the ribosome and then", "the ribosome and then interacts", "ribosome and then interacts with", "and then interacts with pabp", "then interacts with pabp bound", "interacts with pabp bound to", "with pabp bound to the", "pabp bound to the polyadenylate", "bound to the polyadenylate tail", "to the polyadenylate tail of", "the polyadenylate tail of the", "polyadenylate tail of the mrna", "tail of the mrna to", "of the mrna to release", "the mrna to release the", "mrna to release the ribosome", "to release the ribosome and", "release the ribosome and allow", "the ribosome and allow a", "ribosome and allow a new", "and allow a new round", "allow a new round of", "a new round of translation", "new round of translation to", "round of translation to commence.", "of translation to commence. nonsense", "translation to commence. nonsense mediated", "to commence. nonsense mediated decay", "decay nmd is", "nmd is triggered if", "is triggered if erf3 at", "triggered if erf3 at the", "if erf3 at the ribosome", "erf3 at the ribosome interacts", "at the ribosome interacts with", "the ribosome interacts with upf1", "interacts with upf1 which", "with upf1 which may", "upf1 which may compete", "which may compete with pabp", "compete with pabp reviewed", "with pabp reviewed in", "pabp reviewed in isken", "reviewed in isken and maquat", "in isken and maquat 2007", "and maquat 2007 chang", "maquat 2007 chang et", "2007 chang et al.", "et al. 2007 behm", "al. 2007 behm ansmant", "2007 behm ansmant et", "behm ansmant et al. 2007", "et al. 2007 rebbapragada", "al. 2007 rebbapragada and", "2007 rebbapragada and lykke", "rebbapragada and lykke andersen 2009", "lykke andersen 2009 bhuvanagiri", "andersen 2009 bhuvanagiri et", "2009 bhuvanagiri et al.", "et al. 2010 nicholson", "al. 2010 nicholson et", "2010 nicholson et al.", "et al. 2010 durand", "al. 2010 durand and", "2010 durand and lykke", "durand and lykke andersen 2011", "and lykke andersen 2011 .", "lykke andersen 2011 . an", "andersen 2011 . an exon", "2011 . an exon junction", ". an exon junction located", "an exon junction located 50", "exon junction located 50 55", "junction located 50 55 nt", "located 50 55 nt downstream", "50 55 nt downstream of", "55 nt downstream of a", "nt downstream of a termination", "downstream of a termination codon", "of a termination codon is", "a termination codon is observed", "termination codon is observed to", "codon is observed to enhance", "is observed to enhance nmd.
", "observed to enhance nmd.
exon", "to enhance nmd.
exon junction", "enhance nmd.
exon junction complexes", "exon junction complexes ejcs", "complexes ejcs are", "ejcs are deposited on", "are deposited on the mrna", "deposited on the mrna during", "on the mrna during splicing", "the mrna during splicing in", "mrna during splicing in the", "during splicing in the nucleus", "in the nucleus remain", "the nucleus remain on", "nucleus remain on mrnas", "remain on mrnas after transport", "on mrnas after transport to", "mrnas after transport to the", "after transport to the cytosol", "to the cytosol and", "the cytosol and are", "cytosol and are dislodged", "and are dislodged by the", "are dislodged by the ribosome", "dislodged by the ribosome as", "by the ribosome as it", "the ribosome as it progresses", "ribosome as it progresses along", "as it progresses along the", "it progresses along the mrna", "progresses along the mrna during", "along the mrna during the", "the mrna during the pioneer", "mrna during the pioneer round", "during the pioneer round of", "the pioneer round of translation", "round of translation gehring", "of translation gehring et", "translation gehring et al.", "gehring et al. 2009 .", "et al. 2009 . ejcs", "al. 2009 . ejcs contain", "2009 . ejcs contain the", ". ejcs contain the core", "ejcs contain the core factors", "contain the core factors eif4a", "the core factors eif4a iii", "factors eif4a iii magoh", "eif4a iii magoh y14", "magoh y14 and casc3", "y14 and casc3 as", "and casc3 as well as", "casc3 as well as the", "as well as the peripheral", "well as the peripheral factors", "as the peripheral factors rnps1", "peripheral factors rnps1 upf2", "rnps1 upf2 and", "upf2 and upf3. upf2", "and upf3. upf2 and upf3", "upf2 and upf3 recruit", "and upf3 recruit upf1", "upf3 recruit upf1 to", "recruit upf1 to erf3 at", "upf1 to erf3 at the", "to erf3 at the terminating", "erf3 at the terminating ribosome.", "at the terminating ribosome. thus", "the terminating ribosome. thus an", "terminating ribosome. thus an ejc", "ribosome. thus an ejc downstream", "thus an ejc downstream of", "an ejc downstream of a", "ejc downstream of a termination", "of a termination codon will", "a termination codon will not", "termination codon will not have", "codon will not have been", "will not have been dislodged", "not have been dislodged during", "have been dislodged during translation", "been dislodged during translation and", "dislodged during translation and will", "during translation and will recruit", "translation and will recruit upf1", "will recruit upf1 triggering", "recruit upf1 triggering nmd.
upf1", "upf1 triggering nmd.
upf1 is", "triggering nmd.
upf1 is believed to", "nmd.
upf1 is believed to form", "is believed to form a", "believed to form a complex", "to form a complex containing", "form a complex containing smg1", "complex containing smg1 smg8", "smg1 smg8 and", "smg8 and smg9. in", "and smg9. in the key", "smg9. in the key regulatory", "in the key regulatory step", "the key regulatory step of", "key regulatory step of nmd", "regulatory step of nmd smg1", "step of nmd smg1 phosphorylates", "of nmd smg1 phosphorylates upf1.", "nmd smg1 phosphorylates upf1. the", "smg1 phosphorylates upf1. the phosphorylated", "phosphorylates upf1. the phosphorylated upf1", "upf1. the phosphorylated upf1 then", "the phosphorylated upf1 then recruits", "phosphorylated upf1 then recruits either", "upf1 then recruits either smg6", "then recruits either smg6 or", "recruits either smg6 or smg5", "either smg6 or smg5 and", "smg6 or smg5 and smg7.", "or smg5 and smg7. smg6", "smg5 and smg7. smg6 is", "and smg7. smg6 is itself", "smg7. smg6 is itself an", "smg6 is itself an endoribonuclease", "is itself an endoribonuclease that", "itself an endoribonuclease that cleaves", "an endoribonuclease that cleaves the", "endoribonuclease that cleaves the mrna.", "that cleaves the mrna. smg5", "cleaves the mrna. smg5 and", "the mrna. smg5 and smg7", "mrna. smg5 and smg7 do", "smg5 and smg7 do not", "and smg7 do not have", "smg7 do not have endoribonuclease", "do not have endoribonuclease activty", "have endoribonuclease activty but", "endoribonuclease activty but are", "activty but are thought", "but are thought to recruit", "are thought to recruit ribonucleases.", "thought to recruit ribonucleases. nonsense", "to recruit ribonucleases. nonsense mediated", "recruit ribonucleases. nonsense mediated decay", "ribonucleases. nonsense mediated decay has", "nonsense mediated decay has been", "mediated decay has been observed", "decay has been observed to", "has been observed to involve", "been observed to involve deadenlyation", "to involve deadenlyation decapping", "deadenlyation decapping and", "decapping and both 5'", "and both 5' to 3'", "both 5' to 3' and", "5' to 3' and 3'", "to 3' and 3' to", "3' and 3' to 5'", "and 3' to 5' exonuclease", "3' to 5' exonuclease activities", "5' exonuclease activities but", "exonuclease activities but the", "activities but the exact", "but the exact degradative pathways", "the exact degradative pathways taken", "exact degradative pathways taken by", "degradative pathways taken by a", "pathways taken by a given", "taken by a given mrna", "by a given mrna are", "a given mrna are not", "given mrna are not yet", "mrna are not yet known.
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upf1 also", "not yet known.
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initial", "initial event", "event may", "may be", "be aggregation", "aggregation of", "of misfolded", "misfolded or", "or unfolded", "unfolded peptides.", "peptides. early", "early studies", "studies of", "amyloid beta", "beta assembly", "assembly led", "led to", "to a", "a widely", "widely accepted", "accepted model", "model that", "that assembly", "assembly was", "was a", "a nucleation", "nucleation dependent", "dependent polymerization", "polymerization reaction", "teplow 1998", "but it", "it is", "is now", "now understood", "understood to", "to be", "be more", "more complex", "with multiple", "multiple 'off", "'off pathway'", "pathway' events", "events leading", "leading to", "a variety", "variety of", "of oligomeric", "oligomeric structures", "structures in", "in addition", "addition to", "to fibrils", "roychaudhuri et", "al. 2008", "though it", "is unclear", "unclear whether", "whether these", "these intermediate", "intermediate steps", "steps are", "are required", "required in", "in vivo.", "vivo. an", "an increasing", "increasing body", "body of", "of evidence", "evidence suggests", "suggests that", "that these", "these oligomeric", "oligomeric forms", "forms are", "are primarily", "primarily responsible", "responsible for", "for the", "the neurotoxic", "neurotoxic effects", "effects of", "alpha synuclein", "winner et", "al. 2011", "and tau", "dance &", "& strobel", "strobel 2009", "meraz rios", "rios et", ". amyloid", "amyloid oligomers", "oligomers are", "are believed", "believed to", "to have", "have a", "a common", "common structural", "structural motif", "motif that", "that is", "is independent", "independent of", "the protein", "protein involved", "involved and", "and not", "not present", "present in", "in fibrils", "kayed et", "al. 2003", "2003 .", ". conformation", "conformation dependent", "aggregation specific", "specific antibodies", "antibodies suggest", "suggest that", "that there", "there are", "are 3", "3 general", "general classes", "classes 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direction of", "direction of the", "of the fibril", "fibril sawaya", "sawaya et al.", "et al. 2007", "al. 2007 .", "2007 . often", ". often the", "often the fibril", "the fibril has", "fibril has a", "has a left", "a left handed", "left handed twist", "twist nelson", "nelson & eisenberg", "& eisenberg 2006", "eisenberg 2006 .", "2006 . at", ". at least", "at least 27", "least 27 human", "27 human proteins", "human proteins form", "proteins form amyloid", "form amyloid fibrils", "fibrils sipe", "sipe et al.", "et al. 2010", "al. 2010 .", "2010 . many", ". many of", "many of these", "of these proteins", "these proteins have", "proteins have non", "have non pathological", "non pathological functions", "functions the", "the trigger that", "trigger that leads", "that leads to", "leads to abnormal", "to abnormal aggregations", "abnormal aggregations differs", "aggregations differs between", "differs between proteins", "between proteins and", "proteins and is", "and is not", "is not well", 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2003", "al. 2003 .", "2003 . conformation", ". conformation dependent", "dependent aggregation", "aggregation specific antibodies", "specific antibodies suggest", "antibodies suggest that", "suggest that there", "that there are", "there are 3", "are 3 general", "3 general classes", "general classes of", "classes of amyloid", "of amyloid oligomer", "amyloid oligomer structures", "structures glabe", "2009 including", "including annular structures", "annular structures which", "structures which may", "which may be", "may be responsible", "be responsible for", "for the widely", "the widely reported", "widely reported membrane", "reported membrane permeabilization", "membrane permeabilization effect", "permeabilization effect of", "effect of amyloid", "of amyloid oligomers.", "amyloid oligomers. toxicity", "oligomers. toxicity of", "toxicity of amyloid", "of amyloid oligomers", "amyloid oligomers preceeds", "oligomers preceeds the", "preceeds the appearance", "the appearance of", "appearance of plaques", "of plaques in", "plaques in mouse", "in mouse models", "models ferretti", "ferretti et al.", "al. 2011 .", "2011 .
fibrils", ".
fibrils are", "
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2011", "al. 2011 and", "2011 and tau", "and tau dance", "tau dance &", "dance & strobel 2009", "strobel 2009 meraz", "2009 meraz rios", "meraz rios et al.", "rios et al. 2010", "al. 2010 . amyloid", "2010 . amyloid oligomers", ". amyloid oligomers are", "amyloid oligomers are believed", "oligomers are believed to", "are believed to have", "believed to have a", "to have a common", "have a common structural", "a common structural motif", "common structural motif that", "structural motif that is", "motif that is independent", "that is independent of", "is independent of the", "independent of the protein", "of the protein involved", "the protein involved and", "protein involved and not", "involved and not present", "and not present in", "not present in fibrils", "in fibrils kayed", "fibrils kayed et", "kayed et al. 2003", "et al. 2003 .", "al. 2003 . conformation", "2003 . conformation dependent", "conformation dependent aggregation", "dependent aggregation specific", "aggregation specific 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fibrils", "2011 .
fibrils are", ".
fibrils are often", "
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parkinson's", "as alzheimer's parkinson's and", "alzheimer's parkinson's and huntington's.", "parkinson's and huntington's. amyloid deposits", "and huntington's. amyloid deposits consist", "huntington's. amyloid deposits consist predominantly", "amyloid deposits consist predominantly of", "deposits consist predominantly of amyloid", "consist predominantly of amyloid fibrils", "of amyloid fibrils rigid", "fibrils rigid non", "rigid non branching structures", "non branching structures that form", "branching structures that form ordered", "structures that form ordered assemblies", "form ordered assemblies characteristically", "ordered assemblies characteristically with", "assemblies characteristically with a", "characteristically with a cross beta", "with a cross beta sheet", "a cross beta sheet structure", "cross beta sheet structure where", "beta sheet structure where the", "sheet structure where the sheets", "structure where the sheets run", "where the sheets run parallel", "the sheets 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"biochem mol biol", "mol biol 42", "42 2007", "2007 3", "3 14 .", "14 . gaba", ". gaba b", "gaba b receptors", "b receptors are", "receptors are slow", "are slow acting", "slow acting metabotropic", "acting metabotropic gprotein", "metabotropic gprotein coupled", "gprotein coupled receptors", "coupled receptors that", "receptors that act", "that act via", "act via the", "via the inhibitory", "the inhibitory action", "inhibitory action of", "action of their", "of their galpha/go", "their galpha/go subunits", "galpha/go subunits on", "subunits on adenylate", "on adenylate cyclase", "adenylate cyclase to", "cyclase to attenuate", "to attenuate the", "attenuate the actions", "the actions of", "actions of pka.", "of pka. in", "pka. in addition", "addition their", "their gbeta/gamma subunits", "gbeta/gamma subunits interact", "subunits interact directly", "interact directly with", "directly with n", "with n and", "n and p/q", "and p/q ca2+", "p/q ca2+ channels", "ca2+ channels to", "channels 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"subunits interact directly with", "interact directly with n", "directly with n and", "with n and p/q", "n and p/q ca2+", "and p/q ca2+ channels", "p/q ca2+ channels to", "ca2+ channels to decrease", "channels to decrease the", "to decrease the release", "decrease the release of", "the release of ca2+.", "release of ca2+. gaba", "of ca2+. gaba b", "ca2+. gaba b receptors", "gaba b receptors also", "b receptors also interact", "receptors also interact with", "also interact with kir3", "interact with kir3 k+", "with kir3 k+ channels", "kir3 k+ channels and", "k+ channels and increase", "channels and increase the", "and increase the influx", "increase the influx of", "the influx of k+", "of k+ leading", "k+ leading to", "leading to cell membrane", "to cell membrane hyperpolarization", "cell membrane hyperpolarization and", "membrane hyperpolarization and inhibition", "hyperpolarization and inhibition of", "and inhibition of channels", "inhibition of channels such", "of channels such as", 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that", "chloride ion channels that mediate", "ion channels that mediate membrane", "channels that mediate membrane depolarization", "that mediate membrane depolarization and", "mediate membrane depolarization and thus", "membrane depolarization and thus inhibit", "depolarization and thus inhibit neurotransmitter", "and thus inhibit neurotransmitter release", "inhibit neurotransmitter release g", "neurotransmitter release g michels", "release g michels et", "g michels et al crit", "michels et al crit rev", "et al crit rev biochem", "al crit rev biochem mol", "crit rev biochem mol biol", "rev biochem mol biol 42", "mol biol 42 2007", "42 2007 3", "2007 3 14 .", "3 14 . gaba b", "14 . gaba b receptors", ". gaba b receptors are", "gaba b receptors are slow", "b receptors are slow acting", "receptors are slow acting metabotropic", "are slow acting metabotropic gprotein", "slow acting metabotropic gprotein coupled", "acting metabotropic gprotein coupled receptors", "metabotropic gprotein 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2.", "activation.
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complement", ".

complement cascade", "cascade activation", "activation is", "is regulated", "regulated by", "by a", "a family", "family of", "of related", "related proteins", "proteins termed", "termed the", "the regulators", "regulators of", "rca .", ". these", "these are", "are expressed", "expressed on", "on healthy", "healthy host", "host cells.", "cells. most", "most pathogens", "pathogens do", "do not", "not express", "express rca", "rca proteins", "proteins on", "on their", "their surface", "but many", "many have", "have found", "found ways", "ways to", "to evade", "evade the", "the complement", "complement system", "system by", "by stably", "stably binding", "binding the", "the rca", "rca that", "that circulates", "circulates in", "in human", "human plasma", "lambris et", "et al.", "al. 2008", "trapping rca", "rca is", "is by", "by far", "far the", "the most", "most widely", "widely employed", "employed strategy", "strategy for", "for avoiding", "avoiding the", "complement response.", "response. rca", "rca recruitment", "recruitment is", "is common", "common in", "in bacteria", "bacteria such", "such as", "as e.", "e. coli", "coli and", "and streptococci", "kraiczy &", "& wurzner", "wurzner 2006", "and has", "has also", "also been", "been described", "described for", "for viruses", "fungi and", "parasites. rca", "rca deposition", "deposition and", "and the", "system also", "also have", "have an", "an important", "important role", "role in", "in tissue", "tissue homeostasis", "clearing dead", "dead cells", "cells and", "and debris", "and preventing", "preventing damage", "damage from", "from oxidative", "oxidative stress", "weismann et", "al. 2011", "2011 .

rca", ".

rca proteins", "proteins control", "control complement", "activation in", "in two", "two different", "different ways", "by promoting", "promoting the", "the irreversible", "irreversible dissociation", "decay acceleration", "complement convertases", "convertases and", "and by", "by acting", "acting as", "as cofactors", "cofactors for", "for complement", "complement factor", "factor i", "mediated cleavage", "cleavage of", "of c3b", "c3b and", "and c4b.
decay", "c4b.
decay accelerating", "accelerating factor", "factor h", "membrane cofactor", "cofactor protein", "and complement", "complement receptor", "receptor 1", "are composed", "composed of", "of arrays", "arrays of", "of tandem", "tandem globular", "globular domains", "domains termed", "termed ccps", "complement control", "control protein", "protein repeats", "or scrs", "short consensus", "consensus repeats", "repeats .", ". cr1", "mcp and", "and fh", "fh are", "are cofactors", "for the", "the cfi", "cfi mediated", "generating ic3b.", "ic3b. cr1", "cr1 and", "and mcp", "mcp are", "are also", "also cofactors", "for c4b", "c4b cleavage.
", "cleavage.
c4bp", "c4bp is", "an additional", "additional cofactor", "cofactor for", "of c4b.", "two inherent features", "inherent features of", "features of complement", "of complement activation", "complement activation make", "activation make its", "make its regulation", "its regulation very", "regulation very important:", "very important:
1.", "important:
1. there", "
1. there is", "there is an", "is an inherent", "an inherent positive", "inherent positive feedback", "positive feedback loop", "feedback loop because", "loop because the", "because the product", "the product of", "product of c3", "of c3 activation", "c3 activation forms", "activation forms part", "forms part of", "part of an", "of an enzyme", "an enzyme that", "enzyme that causes", "that causes more", "causes more c3", "more c3 activation.
2.", "c3 activation.
2. there", "activation.
2. there is", "there is continuous", "is continuous low", "continuous low level", "low level activation", "level activation of", "activation of the", "of the alternative", "the alternative pathway", "pathway see", "see spontaneous hydrolysis", "spontaneous hydrolysis of", "hydrolysis of c3", "of c3 thioester", "c3 thioester .

complement", "thioester .

complement cascade", ".

complement cascade activation", "cascade activation is", "activation is regulated", "is regulated by", "regulated by a", "by a family", "a family of", "family of related", "of related proteins", "related proteins termed", "proteins termed the", "termed the regulators", "the regulators of", "regulators of complement", "activation rca", "rca . these", ". these are", "these are expressed", "are expressed on", "expressed on healthy", "on healthy host", "healthy host cells.", "host cells. most", "cells. most pathogens", "most pathogens do", "pathogens do not", "do not express", "not express rca", "express rca proteins", "rca proteins on", "proteins on their", "on their surface", "surface but", "but many have", "many have found", "have found ways", "found ways to", "ways to evade", "to evade the", "evade the complement", "the complement system", "complement system by", "system by stably", "by stably binding", "stably binding the", "binding the rca", "the rca that", "rca that circulates", "that circulates in", "circulates in human", "in human plasma", "plasma lambris", "lambris et al.", "et al. 2008", "trapping rca is", "rca is by", "is by far", "by far the", "far the most", "the most widely", "most widely employed", "widely employed strategy", "employed strategy for", "strategy for avoiding", "for avoiding the", "avoiding the complement", "the complement response.", "complement response. rca", "response. rca recruitment", "rca recruitment is", "recruitment is common", "is common in", "common in bacteria", "in bacteria such", "bacteria such as", "such as e.", "as e. coli", "e. coli and", "coli and streptococci", "streptococci kraiczy", "kraiczy & wurzner", "& wurzner 2006", "2006 and", "and has also", "has also been", "also been described", "been described for", "described for viruses", "viruses fungi", "and parasites.", "parasites. rca deposition", "rca deposition and", "deposition and the", "and the complement", "complement system also", "system also have", "also have an", "have an important", "an important role", "important role in", "role in tissue", "in tissue homeostasis", "homeostasis clearing", "clearing dead cells", "dead cells and", "cells and debris", "debris and", "and preventing damage", "preventing damage from", "damage from oxidative", "from oxidative stress", "stress weismann", "weismann et al.", "et al. 2011", "al. 2011 .

rca", "2011 .

rca proteins", ".

rca proteins control", "proteins control complement", "control complement activation", "complement activation in", "activation in two", "in two different", "two different ways", "ways by", "by promoting the", "promoting the irreversible", "the irreversible dissociation", "dissociation decay", "acceleration of", "of complement convertases", "complement convertases and", "convertases and by", "and by acting", "by acting as", "acting as cofactors", "as cofactors for", "cofactors for complement", "for complement factor", "complement factor i", "i cfi", "mediated cleavage of", "cleavage of c3b", "of c3b and", "c3b and c4b.
decay", "and c4b.
decay accelerating", "c4b.
decay accelerating factor", "factor daf", "daf cd55", "complement factor h", "h fh", "membrane cofactor protein", "protein mcp", "and complement receptor", "complement receptor 1", "1 cr1", "cr1 are", "are composed of", "composed of arrays", "of arrays of", "arrays of tandem", "of tandem globular", "tandem globular domains", "globular domains termed", "domains termed ccps", "ccps complement", "complement control protein", "control protein repeats", "repeats or", "scrs short", "short consensus repeats", "consensus repeats .", "repeats . cr1", "cr1 mcp", "mcp and fh", "and fh are", "fh are cofactors", "are cofactors for", "cofactors for the", "for the cfi", "the cfi mediated", "cfi mediated cleavage", "c3b generating", "generating ic3b. cr1", "ic3b. cr1 and", "cr1 and mcp", "and mcp are", "mcp are also", "are also cofactors", "also cofactors for", "cofactors for c4b", "for c4b cleavage.
", "c4b cleavage.
c4bp", "cleavage.
c4bp is", "c4bp is an", "is an additional", "an additional cofactor", "additional cofactor for", "cofactor for the", "cleavage of c4b.", "two inherent features of", "inherent features of complement", "features of complement activation", "of complement activation make", "complement activation make its", "activation make its regulation", "make its regulation very", "its regulation very important:", "regulation very important:
1.", "very important:
1. there", "important:
1. there is", "
1. there is an", "there is an inherent", "is an inherent positive", "an inherent positive feedback", "inherent positive feedback loop", "positive feedback loop because", "feedback loop because the", "loop because the product", "because the product of", "the product of c3", "product of c3 activation", "of c3 activation forms", "c3 activation forms part", "activation forms part of", "forms part of an", "part of an enzyme", "of an enzyme that", "an enzyme that causes", "enzyme that causes more", "that causes more c3", "causes more c3 activation.
2.", "more c3 activation.
2. there", "c3 activation.
2. there is", "activation.
2. there is continuous", "there is continuous low", "is continuous low level", "continuous low level activation", "low level activation of", "level activation of the", "activation of the alternative", "of the alternative pathway", "alternative pathway see", "pathway see spontaneous", "see spontaneous hydrolysis of", "spontaneous hydrolysis of c3", "hydrolysis of c3 thioester", "of c3 thioester .

complement", "c3 thioester .

complement cascade", "thioester .

complement cascade activation", ".

complement cascade activation is", "cascade activation is regulated", "activation is regulated by", "is regulated by a", "regulated by a family", "by a family of", "a family of related", "family of related proteins", "of related proteins termed", "related proteins termed the", "proteins termed the regulators", "termed the regulators of", "the regulators of complement", "regulators of complement activation", "complement activation rca", "activation rca .", "rca . these are", ". these are expressed", "these are expressed on", "are expressed on healthy", "expressed on healthy host", "on healthy host cells.", "healthy host cells. most", "host cells. most pathogens", "cells. most pathogens do", "most pathogens do not", "pathogens do not express", "do not express rca", "not express rca proteins", "express rca proteins on", "rca proteins on their", "proteins on their surface", "their surface but", "surface but many", "but many have found", "many have found ways", "have found ways to", "found ways to evade", "ways to evade the", "to evade the complement", "evade the complement system", "the complement system by", "complement system by stably", "system by stably binding", "by stably binding the", "stably binding the rca", "binding the rca that", "the rca that circulates", "rca that circulates in", "that circulates in human", "circulates in human plasma", "human plasma lambris", "plasma lambris et", "lambris et al. 2008", "2008 trapping", "trapping rca is by", "rca is by far", "is by far the", "by far the most", "far the most widely", "the most widely employed", "most widely employed strategy", "widely employed strategy for", "employed strategy for avoiding", "strategy for avoiding the", "for avoiding the complement", "avoiding the complement response.", "the complement response. rca", "complement response. rca recruitment", "response. rca recruitment is", "rca recruitment is common", "recruitment is common in", "is common in bacteria", "common in bacteria such", "in bacteria such as", "bacteria such as e.", "such as e. coli", "as e. coli and", "e. coli and streptococci", "and streptococci kraiczy", "streptococci kraiczy &", "kraiczy & wurzner 2006", "wurzner 2006 and", "2006 and has", "and has also been", "has also been described", "also been described for", "been described for viruses", "for viruses fungi", "viruses fungi and", "fungi and parasites.", "and parasites. rca", "parasites. rca deposition and", "rca deposition and the", "deposition and the complement", "and the complement system", "the complement system also", "complement system also have", "system also have an", "also have an important", "have an important role", "an important role in", "important role in tissue", "role in tissue homeostasis", "tissue homeostasis clearing", "homeostasis clearing dead", "clearing dead cells and", "dead cells and debris", "and debris and", "debris and preventing", "and preventing damage from", "preventing damage from oxidative", "damage from oxidative stress", "oxidative stress weismann", "stress weismann et", "weismann et al. 2011", "et al. 2011 .

rca", "al. 2011 .

rca proteins", "2011 .

rca proteins control", ".

rca proteins control complement", "proteins control complement activation", "control complement activation in", "complement activation in two", "activation in two different", "in two different ways", "different ways by", "ways by promoting", "by promoting the irreversible", "promoting the irreversible dissociation", "irreversible dissociation decay", "dissociation decay acceleration", "decay acceleration of", "acceleration of complement", "of complement convertases and", "complement convertases and by", "convertases and by acting", "and by acting as", "by acting as cofactors", "acting as cofactors for", "as cofactors for complement", "cofactors for complement factor", "for complement factor i", "factor i cfi", "mediated cleavage of c3b", "cleavage of c3b and", "of c3b and c4b.
decay", "c3b and c4b.
decay accelerating", "and c4b.
decay accelerating factor", "accelerating factor daf", "cd55 complement", "factor h fh", "fh membrane", "cofactor protein mcp", "mcp and complement", "and complement receptor 1", "receptor 1 cr1", "cr1 are composed", "are composed of arrays", "composed of arrays of", "of arrays of tandem", "arrays of tandem globular", "of tandem globular domains", "tandem globular domains termed", "globular domains termed ccps", "termed ccps complement", "ccps complement control", "complement control protein repeats", "protein repeats or", "repeats or scrs", "or scrs short", "scrs short consensus", "short consensus repeats .", "consensus repeats . cr1", ". cr1 mcp", "cr1 mcp and", "mcp and fh are", "and fh are cofactors", "fh are cofactors for", "are cofactors for the", "cofactors for the cfi", "for the cfi mediated", "the cfi mediated cleavage", "cfi mediated cleavage of", "of c3b generating", "c3b generating ic3b.", "generating ic3b. cr1 and", "ic3b. cr1 and mcp", "cr1 and mcp are", "and mcp are also", "mcp are also cofactors", "are also cofactors for", "also cofactors for c4b", "cofactors for c4b cleavage.
", "for c4b cleavage.
c4bp", "c4b cleavage.
c4bp is", "cleavage.
c4bp is an", "c4bp is an additional", "is an additional cofactor", "an additional cofactor for", "additional cofactor for the", "cofactor for the cfi", "mediated cleavage of c4b.", "two inherent features of complement", "inherent features of complement activation", "features of complement activation make", "of complement activation make its", "complement activation make its regulation", "activation make its regulation very", "make its regulation very important:", "its regulation very important:
1.", "regulation very important:
1. there", "very important:
1. there is", "important:
1. there is an", "
1. there is an inherent", "there is an inherent positive", "is an inherent positive feedback", "an inherent positive feedback loop", "inherent positive feedback loop because", "positive feedback loop because the", "feedback loop because the product", "loop because the product of", "because the product of c3", "the product of c3 activation", "product of c3 activation forms", "of c3 activation forms part", "c3 activation forms part of", "activation forms part of an", "forms part of an enzyme", "part of an enzyme that", "of an enzyme that causes", "an enzyme that causes more", "enzyme that causes more c3", "that causes more c3 activation.
2.", "causes more c3 activation.
2. there", "more c3 activation.
2. there is", "c3 activation.
2. there is continuous", "activation.
2. there is continuous low", "there is continuous low level", "is continuous low level activation", "continuous low level activation of", "low level activation of the", "level activation of the alternative", "activation of the alternative pathway", "the alternative pathway see", "alternative pathway see spontaneous", "pathway see spontaneous hydrolysis", "see spontaneous hydrolysis of c3", "spontaneous hydrolysis of c3 thioester", "hydrolysis of c3 thioester .

complement", "of c3 thioester .

complement cascade", "c3 thioester .

complement cascade activation", "thioester .

complement cascade activation is", ".

complement cascade activation is regulated", "cascade activation is regulated by", "activation is regulated by a", "is regulated by a family", "regulated by a family of", "by a family of related", "a family of related proteins", "family of related proteins termed", "of related proteins termed the", "related proteins termed the regulators", "proteins termed the regulators of", "termed the regulators of complement", "the regulators of complement activation", "of complement activation rca", "complement activation rca .", "activation rca . these", "rca . these are expressed", ". these are expressed on", "these are expressed on healthy", "are expressed on healthy host", "expressed on healthy host cells.", "on healthy host cells. most", "healthy host cells. most pathogens", "host cells. most pathogens do", "cells. most pathogens do not", "most pathogens do not express", "pathogens do not express rca", "do not express rca proteins", "not express rca proteins on", "express rca proteins on their", "rca proteins on their surface", "on their surface but", "their surface but many", "surface but many have", "but many have found ways", "many have found ways to", "have found ways to evade", "found ways to evade the", "ways to evade the complement", "to evade the complement system", "evade the complement system by", "the complement system by stably", "complement system by stably binding", "system by stably binding the", "by stably binding the rca", "stably binding the rca that", "binding the rca that circulates", "the rca that circulates in", "rca that circulates in human", "that circulates in human plasma", "in human plasma lambris", "human plasma lambris et", "plasma lambris et al.", "al. 2008 trapping", "2008 trapping rca", "trapping rca is by far", "rca is by far the", "is by far the most", "by far the most widely", "far the most widely employed", "the most widely employed strategy", "most widely employed strategy for", "widely employed strategy for avoiding", "employed strategy for avoiding the", "strategy for avoiding the complement", "for avoiding the complement response.", "avoiding the complement response. rca", "the complement response. rca recruitment", "complement response. rca recruitment is", "response. rca recruitment is common", "rca recruitment is common in", "recruitment is common in bacteria", "is common in bacteria such", "common in bacteria such as", "in bacteria such as e.", "bacteria such as e. coli", "such as e. coli and", "as e. coli and streptococci", "coli and streptococci kraiczy", "and streptococci kraiczy &", "streptococci kraiczy & wurzner", "& wurzner 2006 and", "wurzner 2006 and has", "2006 and has also", "and has also been described", "has also been described for", "also been described for viruses", "described for viruses fungi", "for viruses fungi and", "fungi and parasites. rca", "and parasites. rca deposition", "parasites. rca deposition and the", "rca deposition and the complement", "deposition and the complement system", "and the complement system also", "the complement system also have", "complement system also have an", "system also have an important", "also have an important role", "have an important role in", "an important role in tissue", "important role in tissue homeostasis", "in tissue homeostasis clearing", "tissue homeostasis clearing dead", "homeostasis clearing dead cells", "clearing dead cells and debris", "cells and debris and", "and debris and preventing", "debris and preventing damage", "and preventing damage from oxidative", "preventing damage from oxidative stress", "from oxidative stress weismann", "oxidative stress weismann et", "stress weismann et al.", "weismann et al. 2011 .

rca", "et al. 2011 .

rca proteins", "al. 2011 .

rca proteins control", "2011 .

rca proteins control complement", ".

rca proteins control complement activation", "proteins control complement activation in", "control complement activation in two", "complement activation in two different", "activation in two different ways", "two different ways by", "different ways by promoting", "ways by promoting the", "by promoting the irreversible dissociation", "the irreversible dissociation decay", "irreversible dissociation decay acceleration", "decay acceleration of complement", "acceleration of complement convertases", "of complement convertases and by", "complement convertases and by acting", "convertases and by acting as", "and by acting as cofactors", "by acting as cofactors for", "acting as cofactors for complement", "as cofactors for complement factor", "cofactors for complement factor i", "complement factor i cfi", "i cfi mediated", "mediated cleavage of c3b and", "cleavage of c3b and c4b.
decay", "of c3b and c4b.
decay accelerating", "c3b and c4b.
decay accelerating factor", "c4b.
decay accelerating factor daf", "factor daf cd55", "cd55 complement factor", "complement factor h fh", "fh membrane cofactor", "membrane cofactor protein mcp", "protein mcp and", "mcp and complement receptor", "complement receptor 1 cr1", "1 cr1 are", "cr1 are composed of", "are composed of arrays of", "composed of arrays of tandem", "of arrays of tandem globular", "arrays of tandem globular domains", "of tandem globular domains termed", "tandem globular domains termed ccps", "domains termed ccps complement", "termed ccps complement control", "ccps complement control protein", "control protein repeats or", "protein repeats or scrs", "or scrs short consensus", "scrs short consensus repeats", "short consensus repeats . cr1", "repeats . cr1 mcp", ". cr1 mcp and", "cr1 mcp and fh", "mcp and fh are cofactors", "and fh are cofactors for", "fh are cofactors for the", "are cofactors for the cfi", "cofactors for the cfi mediated", "for the cfi mediated cleavage", "the cfi mediated cleavage of", "cfi mediated cleavage of c3b", "cleavage of c3b generating", "of c3b generating ic3b.", "c3b generating ic3b. cr1", "generating ic3b. cr1 and mcp", "ic3b. cr1 and mcp are", "cr1 and mcp are also", "and mcp are also cofactors", "mcp are also cofactors for", "are also cofactors for c4b", "also cofactors for c4b cleavage.
", "cofactors for c4b cleavage.
c4bp", "for c4b cleavage.
c4bp is", "c4b cleavage.
c4bp is an", "cleavage.
c4bp is an additional", "c4bp is an additional cofactor", "is an additional cofactor for", "an additional cofactor for the", "additional cofactor for the cfi", "cofactor for the cfi mediated", "cfi mediated cleavage of c4b." ] }, { "record_id": "GLY_000594_1_711", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "982772", "r hsa", "hsa 982772", "r hsa 982772" ] }, { "record_id": "GLY_000594_1_711", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "growth hormone", "hormone receptor", "receptor signaling", "growth hormone receptor", "hormone receptor signaling", "growth hormone receptor signaling", "somatotropin or", "or gh", "is a", "a key", "key factor", "factor in", "in determining", "determining lean", "lean body", "body mass", "stimulating the", "the growth", "growth and", "and metabolism", "metabolism of", "of muscle", "bone and", "and cartilage", "cartilage cells", "while reducing", "reducing body", "body fat.", "fat. it", "it has", "has many", "many other", "other roles", "it acts", "acts to", "to regulate", "regulate cell", "cell growth", "and reorganisation", "reorganisation of", "of the", "the cytoskeleton", "affecting diverse", "diverse processes", "processes such", "such as", "as cardiac", "cardiac function", "immune function", "brain function", "and aging.", "gh also", "also has", "has insulin", "insulin like", "like effects", "effects such", "as stimulating", "stimulating amino", "amino acid", "acid transport", "protein synthesis", "glucose transport", "and lipogenesis.", "lipogenesis. the", "a a", "a member", "member of", "the cytokine", "cytokine receptor", "receptor family.", "family. when", "when the", "the dimeric", "dimeric receptor", "receptor binds", "binds gh", "gh it", "it undergoes", "undergoes a", "a conformational", "conformational change", "change which", "which leads", "leads to", "to phosphorylation", "phosphorylation of", "of key", "key tyrosine", "tyrosine residues", "residues in", "in its", "its cytoplasmic", "cytoplasmic domains", "domains and", "and activation", "activation of", "of associated", "associated tyrosine", "tyrosine kinase", "kinase jak2.", "jak2. this", "this leads", "to recruitment", "recruitment of", "of signaling", "signaling molecules", "molecules such", "as stat5", "stat5 and", "and src", "src family", "family kinases", "kinases such", "as lyn", "lyn leading", "leading to", "to erk", "erk activation.", "activation. the", "the signal", "signal is", "is attenuated", "attenuated by", "by association", "association of", "of suppressor", "suppressor of", "of cytokine", "cytokine signaling", "proteins and", "and shp", "shp phosphatases", "phosphatases which", "which bind", "bind to", "to or", "or dephosphorylate", "dephosphorylate specific", "specific phosphorylated", "phosphorylated tyrosines", "tyrosines on", "on ghr/jak.", "ghr/jak. the", "the availability", "availability of", "of ghr", "ghr on", "on the", "the cell", "cell surface", "surface is", "is regulated", "regulated by", "by at", "at least", "least two", "two processes", "internalization and", "and cleavage", "cleavage from", "from the", "the suface", "suface by", "by metalloproteases.", "hormone somatotropin", "somatotropin or gh", "gh is", "is a key", "a key factor", "key factor in", "factor in determining", "in determining lean", "determining lean body", "lean body mass", "mass stimulating", "stimulating the growth", "the growth and", "growth and metabolism", "and metabolism of", "metabolism of muscle", "muscle bone", "bone and cartilage", "and cartilage cells", "cells while", "while reducing body", "reducing body fat.", "body fat. it", "fat. it has", "it has many", "has many other", "many other roles", "roles it", "it acts to", "acts to regulate", "to regulate cell", "regulate cell growth", "growth differentiation", "differentiation apoptosis", "apoptosis and", "and reorganisation of", "reorganisation of the", "of the cytoskeleton", "cytoskeleton affecting", "affecting diverse processes", "diverse processes such", "processes such as", "such as cardiac", "as cardiac function", "function immune", "function brain", "function and", "aging. gh", "gh also has", "also has insulin", "has insulin like", "insulin like effects", "like effects such", "effects such as", "such as stimulating", "as stimulating amino", "stimulating amino acid", "amino acid transport", "transport protein", "synthesis glucose", "transport and", "and lipogenesis. the", "lipogenesis. the growth", "the growth hormone", "receptor ghr", "ghr is", "is a a", "a a member", "a member of", "member of the", "of the cytokine", "the cytokine receptor", "cytokine receptor family.", "receptor family. when", "family. when the", "when the dimeric", "the dimeric receptor", "dimeric receptor binds", "receptor binds gh", "binds gh it", "gh it undergoes", "it undergoes a", "undergoes a conformational", "a conformational change", "conformational change which", "change which leads", "which leads to", "leads to phosphorylation", "to phosphorylation of", "phosphorylation of key", "of key tyrosine", "key tyrosine residues", "tyrosine residues in", "residues in its", "in its cytoplasmic", "its cytoplasmic domains", "cytoplasmic domains and", "domains and activation", "and activation of", "activation of associated", "of associated tyrosine", "associated tyrosine kinase", "tyrosine kinase jak2.", "kinase jak2. this", "jak2. this leads", "this leads to", "leads to recruitment", "to recruitment of", "recruitment of signaling", "of signaling molecules", "signaling molecules such", "molecules such as", "such as stat5", "as stat5 and", "stat5 and src", "and src family", "src family kinases", "family kinases such", "kinases such as", "such as lyn", "as lyn leading", "lyn leading to", "leading to erk", "to erk activation.", "erk activation. the", "activation. the signal", "the signal is", "signal is attenuated", "is attenuated by", "attenuated by association", "by association of", "association of suppressor", "of suppressor of", "suppressor of cytokine", "of cytokine signaling", "signaling socs", "socs proteins", "proteins and shp", "and shp phosphatases", "shp phosphatases which", "phosphatases which bind", "which bind to", "bind to or", "to or dephosphorylate", "or dephosphorylate specific", "dephosphorylate specific phosphorylated", "specific phosphorylated tyrosines", "phosphorylated tyrosines on", "tyrosines on ghr/jak.", "on ghr/jak. the", "ghr/jak. the availability", "the availability of", "availability of ghr", "of ghr on", "ghr on the", "on the cell", "the cell surface", "cell surface is", "surface is regulated", "is regulated by", "regulated by at", "by at least", "at least two", "least two processes", "processes internalization", "internalization and cleavage", "and cleavage from", "cleavage from the", "from the suface", "the suface by", "suface by metalloproteases.", "growth hormone somatotropin", "hormone somatotropin or", "or gh is", "gh is a", "is a key factor", "a key factor in", "key factor in determining", "factor in determining lean", "in determining lean body", "determining lean body mass", "body mass stimulating", "mass stimulating the", "stimulating the growth and", "the growth and metabolism", "growth and metabolism of", "and metabolism of muscle", "of muscle bone", "muscle bone and", "bone and cartilage cells", "cartilage cells while", "cells while reducing", "while reducing body fat.", "reducing body fat. it", "body fat. it has", "fat. it has many", "it has many other", "has many other roles", "other roles it", "roles it acts", "it acts to regulate", "acts to regulate cell", "to regulate cell growth", "cell growth differentiation", "apoptosis and reorganisation", "and reorganisation of the", "reorganisation of the cytoskeleton", "the cytoskeleton affecting", "cytoskeleton affecting diverse", "affecting diverse processes such", "diverse processes such as", "processes such as cardiac", "such as cardiac function", "cardiac function immune", "function immune function", "immune function brain", "function brain function", "brain function and", "function and aging.", "and aging. gh", "aging. gh also", "gh also has insulin", "also has insulin like", "has insulin like effects", "insulin like effects such", "like effects such as", "effects such as stimulating", "such as stimulating amino", "as stimulating amino acid", "stimulating amino acid transport", "acid transport protein", "transport protein synthesis", "protein synthesis glucose", "synthesis glucose transport", "glucose transport and", "transport and lipogenesis.", "and lipogenesis. the growth", "lipogenesis. the growth hormone", "the growth hormone receptor", "hormone receptor ghr", "ghr is a", "is a a member", "a a member of", "a member of the", "member of the cytokine", "of the cytokine receptor", "the cytokine receptor family.", "cytokine receptor family. when", "receptor family. when the", "family. when the dimeric", "when the dimeric receptor", "the dimeric receptor binds", "dimeric receptor binds gh", "receptor binds gh it", "binds gh it undergoes", "gh it undergoes a", "it undergoes a conformational", "undergoes a conformational change", "a conformational change which", "conformational change which leads", "change which leads to", "which leads to phosphorylation", "leads to phosphorylation of", "to phosphorylation of key", "phosphorylation of key tyrosine", "of key tyrosine residues", "key tyrosine residues in", "tyrosine residues in its", "residues in its cytoplasmic", "in its cytoplasmic domains", "its cytoplasmic domains and", "cytoplasmic domains and activation", "domains and activation of", "and activation of associated", "activation of associated tyrosine", "of associated tyrosine kinase", "associated tyrosine kinase jak2.", "tyrosine kinase jak2. this", "kinase jak2. this leads", "jak2. this leads to", "this leads to recruitment", "leads to recruitment of", "to recruitment of signaling", "recruitment of signaling molecules", "of signaling molecules such", "signaling molecules such as", "molecules such as stat5", "such as stat5 and", "as stat5 and src", "stat5 and src family", "and src family kinases", "src family kinases such", "family kinases such as", "kinases such as lyn", "such as lyn leading", "as lyn leading to", "lyn leading to erk", "leading to erk activation.", "to erk activation. the", "erk activation. the signal", "activation. the signal is", "the signal is attenuated", "signal is attenuated by", "is attenuated by association", "attenuated by association of", "by association of suppressor", "association of suppressor of", "of suppressor of cytokine", "suppressor of cytokine signaling", "cytokine signaling socs", "socs proteins and", "proteins and shp phosphatases", "and shp phosphatases which", "shp phosphatases which bind", "phosphatases which bind to", "which bind to or", "bind to or dephosphorylate", "to or dephosphorylate specific", "or dephosphorylate specific phosphorylated", "dephosphorylate specific phosphorylated tyrosines", "specific phosphorylated tyrosines on", "phosphorylated tyrosines on ghr/jak.", "tyrosines on ghr/jak. the", "on ghr/jak. the availability", "ghr/jak. the availability of", "the availability of ghr", "availability of ghr on", "of ghr on the", "ghr on the cell", "on the cell surface", "the cell surface is", "cell surface is regulated", "surface is regulated by", "is regulated by at", "regulated by at least", "by at least two", "at least two processes", "two processes internalization", "processes internalization and", "internalization and cleavage from", "and cleavage from the", "cleavage from the suface", "from the suface by", "the suface by metalloproteases.", "growth hormone somatotropin or", "hormone somatotropin or gh", "somatotropin or gh is", "or gh is a", "gh is a key", "is a key factor in", "a key factor in determining", "key factor in determining lean", "factor in determining lean body", "in determining lean body mass", "lean body mass stimulating", "body mass stimulating the", "mass stimulating the growth", "stimulating the growth and metabolism", "the growth and metabolism of", "growth and metabolism of muscle", "metabolism of muscle bone", "of muscle bone and", "muscle bone and cartilage", "and cartilage cells while", "cartilage cells while reducing", "cells while reducing body", "while reducing body fat. it", "reducing body fat. it has", "body fat. it has many", "fat. it has many other", "it has many other roles", "many other roles it", "other roles it acts", "roles it acts to", "it acts to regulate cell", "acts to regulate cell growth", "regulate cell growth differentiation", "growth differentiation apoptosis", "differentiation apoptosis and", "apoptosis and reorganisation of", "and reorganisation of the cytoskeleton", "of the cytoskeleton affecting", "the cytoskeleton affecting diverse", "cytoskeleton affecting diverse processes", "affecting diverse processes such as", "diverse processes such as cardiac", "processes such as cardiac function", "as cardiac function immune", "cardiac function immune function", "immune function brain function", "brain function and aging.", "and aging. gh also", "aging. gh also has", "gh also has insulin like", "also has insulin like effects", "has insulin like effects such", "insulin like effects such as", "like effects such as stimulating", "effects such as stimulating amino", "such as stimulating amino acid", "as stimulating amino acid transport", "amino acid transport protein", "acid transport protein synthesis", "protein synthesis glucose transport", "glucose transport and lipogenesis.", "transport and lipogenesis. the", "and lipogenesis. the growth hormone", "lipogenesis. the growth hormone receptor", "growth hormone receptor ghr", "receptor ghr is", "ghr is a a", "is a a member of", "a a member of the", "a member of the cytokine", "member of the cytokine receptor", "of the cytokine receptor family.", "the cytokine receptor family. when", "cytokine receptor family. when the", "receptor family. when the dimeric", "family. when the dimeric receptor", "when the dimeric receptor binds", "the dimeric receptor binds gh", "dimeric receptor binds gh it", "receptor binds gh it undergoes", "binds gh it undergoes a", "gh it undergoes a conformational", "it undergoes a conformational change", "undergoes a conformational change which", "a conformational change which leads", "conformational change which leads to", "change which leads to phosphorylation", "which leads to phosphorylation of", "leads to phosphorylation of key", "to phosphorylation of key tyrosine", "phosphorylation of key tyrosine residues", "of key tyrosine residues in", "key tyrosine residues in its", "tyrosine residues in its cytoplasmic", "residues in its cytoplasmic domains", "in its cytoplasmic domains and", "its cytoplasmic domains and activation", "cytoplasmic domains and activation of", "domains and activation of associated", "and activation of associated tyrosine", "activation of associated tyrosine kinase", "of associated tyrosine kinase jak2.", "associated tyrosine kinase jak2. this", "tyrosine kinase jak2. this leads", "kinase jak2. this leads to", "jak2. this leads to recruitment", "this leads to recruitment of", "leads to recruitment of signaling", "to recruitment of signaling molecules", "recruitment of signaling molecules such", "of signaling molecules such as", "signaling molecules such as stat5", "molecules such as stat5 and", "such as stat5 and src", "as stat5 and src family", "stat5 and src family kinases", "and src family kinases such", "src family kinases such as", "family kinases such as lyn", "kinases such as lyn leading", "such as lyn leading to", "as lyn leading to erk", "lyn leading to erk activation.", "leading to erk activation. the", "to erk activation. the signal", "erk activation. the signal is", "activation. the signal is attenuated", "the signal is attenuated by", "signal is attenuated by association", "is attenuated by association of", "attenuated by association of suppressor", "by association of suppressor of", "association of suppressor of cytokine", "of suppressor of cytokine signaling", "of cytokine signaling socs", "signaling socs proteins", "socs proteins and shp", "proteins and shp phosphatases which", "and shp phosphatases which bind", "shp phosphatases which bind to", "phosphatases which bind to or", "which bind to or dephosphorylate", "bind to or dephosphorylate specific", "to or dephosphorylate specific phosphorylated", "or dephosphorylate specific phosphorylated tyrosines", "dephosphorylate specific phosphorylated tyrosines on", "specific phosphorylated tyrosines on ghr/jak.", "phosphorylated tyrosines on ghr/jak. the", "tyrosines on ghr/jak. the availability", "on ghr/jak. the availability of", "ghr/jak. the availability of ghr", "the availability of ghr on", "availability of ghr on the", "of ghr on the cell", "ghr on the cell surface", "on the cell surface is", "the cell surface is regulated", "cell surface is regulated by", "surface is regulated by at", "is regulated by at least", "regulated by at least two", "by at least two processes", "least two processes internalization", "two processes internalization and", "processes internalization and cleavage", "internalization and cleavage from the", "and cleavage from the suface", "cleavage from the suface by", "from the suface by metalloproteases." ] }, { "record_id": "GLY_000594_1_712", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "983168", "r hsa", "hsa 983168", "r hsa 983168" ] }, { "record_id": "GLY_000594_1_712", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "antigen processing:", "processing: ubiquitination", "ubiquitination &", "& proteasome", "proteasome degradation", "antigen processing: ubiquitination", "processing: ubiquitination &", "ubiquitination & proteasome", "& proteasome degradation", "antigen processing: ubiquitination &", "processing: ubiquitination & proteasome", "ubiquitination & proteasome degradation", "antigen processing: ubiquitination & proteasome", "processing: ubiquitination & proteasome degradation", "intracellular foreign", "foreign or", "or aberrant", "aberrant host", "host proteins", "proteins are", "are cleaved", "cleaved into", "into peptide", "peptide fragments", "fragments of", "of a", "a precise", "precise size", "such that", "that they", "they can", "can be", "be loaded", "loaded on", "on to", "to class", "class i", "i mhc", "mhc molecules", "molecules and", "and presented", "presented externally", "externally to", "to cytotoxic", "cytotoxic t", "t cells.", "cells. the", "the ubiquitin", "ubiquitin 26s", "26s proteasome", "proteasome system", "system plays", "plays a", "a central", "central role", "role in", "in the", "the generation", "generation of", "of these", "these class", "mhc antigens.", "antigens.
ubiquitination", "
ubiquitination is", "is the", "the mechanism", "mechanism of", "of adding", "adding ubiquitin", "ubiquitin to", "to lysine", "lysine residues", "residues on", "on substrate", "substrate protein", "protein leading", "leading to", "to the", "the formation", "formation of", "a polyubiquitinated", "polyubiquitinated substrate.", "substrate. this", "this process", "process involves", "involves three", "three classes", "classes of", "of enzyme", "an e1", "e1 ubiquitin", "ubiquitin activating", "activating enzyme", "an e2", "e2 ubiquitin", "ubiquitin conjugating", "conjugating enzyme", "and an", "an e3", "e3 ubiquitin", "ubiquitin ligase.", "ligase. polyubiquitination", "polyubiquitination through", "through lysine", "lysine 48", "generally targets", "targets the", "the substrate", "protein for", "for proteasomal", "proteasomal destruction.", "destruction. the", "the protease", "protease responsible", "responsible for", "for the", "the degradation", "degradation of", "of k48", "k48 polyubiquitinated", "polyubiquitinated proteins", "proteins is", "the 26s", "26s proteasome.", "proteasome. this", "this proteasome", "proteasome is", "is a", "a two", "two subunit", "subunit protein", "protein complex", "complex composed", "composed of", "of the", "the 20s", "catalytic core", "core particle", "and 19s", "regulatory particle", "proteasome complexes.", "complexes. the", "the proteasome", "proteasome eliminates", "eliminates most", "most of", "the foreign", "foreign and", "and non", "non functional", "functional proteins", "proteins from", "from the", "the cell", "cell by", "by degrading", "degrading them", "them into", "into short", "short peptides", "only a", "a small", "small fraction", "fraction of", "the peptides", "peptides generated", "generated are", "are of", "the correct", "correct length", "length to", "to be", "be presented", "presented by", "by the", "the mhc", "mhc class", "i system.", "system. it", "it has", "has been", "been calculated", "calculated that", "that between", "between 994", "994 and", "and 3122", "3122 protein", "protein molecules", "molecules have", "have to", "be degraded", "degraded for", "a single", "stable mhc", "i complex", "complex at", "at the", "cell surface", "with an", "an average", "average efficiency", "efficiency of", "of 1", "1 in", "in 2000", "kloetzel et", "et al.", "al. 2004", "princiotta et", "al. 2003", "2003 .", "intracellular foreign or", "foreign or aberrant", "or aberrant host", "aberrant host proteins", "host proteins are", "proteins are cleaved", "are cleaved into", "cleaved into peptide", "into peptide fragments", "peptide fragments of", "fragments of a", "of a precise", "a precise size", "size such", "such that they", "that they can", "they can be", "can be loaded", "be loaded on", "loaded on to", "on to class", "to class i", "class i mhc", "i mhc molecules", "mhc molecules and", "molecules and presented", "and presented externally", "presented externally to", "externally to cytotoxic", "to cytotoxic t", "cytotoxic t cells.", "t cells. the", "cells. the ubiquitin", "the ubiquitin 26s", "ubiquitin 26s proteasome", "26s proteasome system", "proteasome system plays", "system plays a", "plays a central", "a central role", "central role in", "role in the", "in the generation", "the generation of", "generation of these", "of these class", "these class i", "i mhc antigens.", "mhc antigens.
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richardson", "richardson et al.", "mks give rise", "give rise to circulating", "rise to circulating platelets", "circulating platelets thrombocytes", "thrombocytes through terminal", "through terminal differentiation of", "terminal differentiation of mks", "differentiation of mks which", "of mks which release", "mks which release cytoplasmic", "which release cytoplasmic fragments", "release cytoplasmic fragments as", "cytoplasmic fragments as circulating", "fragments as circulating platelets.", "as circulating platelets. as", "circulating platelets. as mks", "platelets. as mks mature", "as mks mature they", "mks mature they undergo", "mature they undergo endoreduplication", "undergo endoreduplication polyploidisation", "polyploidisation and expansion", "and expansion of cytoplasmic", "expansion of cytoplasmic mass", "of cytoplasmic mass to", "cytoplasmic mass to cell", "mass to cell sizes", "to cell sizes larger", "cell sizes larger than", "sizes larger than 50", "larger than 50 100", "than 50 100 microns", "100 microns and", "microns and ploidy", "and ploidy ranges up", "ploidy ranges up to", "ranges up to 128", "up to 128 n.", "to 128 n. as", "128 n. as mks", "n. as mks mature", "mks mature the", "mature the polyploid", "the polyploid nucleus becomes", "polyploid nucleus becomes horseshoe", "nucleus becomes horseshoe shaped", "horseshoe shaped the", "shaped the cytoplasm", "cytoplasm expands and", "expands and platelet", "and platelet organelles and", "platelet organelles and the", "organelles and the demarcation", "and the demarcation membrane", "the demarcation membrane system", "demarcation membrane system are", "membrane system are amplified.", "system are amplified. proplatelet", "are amplified. proplatelet projections", "amplified. proplatelet projections form", "proplatelet projections form which", "projections form which give", "form which give rise", "which give rise to", "give rise to de", "rise to de novo", "to de novo circulating", "de novo circulating platelets", "circulating platelets deutsch", "platelets deutsch &", "deutsch & tomer 2006", "& tomer 2006 .", "2006 .
the", ".
the processes", "
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differentiation", "proliferation differentiation and", "differentiation and platelet release", "platelet release kaushansky", "release kaushansky 2003", "kaushansky 2003 . thrombopoietin", ". thrombopoietin tpo/c", "thrombopoietin tpo/c mpl", "mpl ligand is", "ligand is the", "is the most potent", "the most potent cytokine", "most potent cytokine stimulating", "potent cytokine stimulating proliferation", "cytokine stimulating proliferation and", "stimulating proliferation and maturation", "proliferation and maturation of", "and maturation of mk", "maturation of mk progenitors", "mk progenitors kaushansky", "progenitors kaushansky 2005", "kaushansky 2005 but", "2005 but many", "but many other growth", "many other growth factors", "other growth factors are", "growth factors are involved.", "factors are involved. mk", "are involved. mk development", "involved. mk development is", "mk development is controlled", "development is controlled by", "is controlled by the", "controlled by the action", "by the action of", "the action of multiple", "action of multiple transcription", "of multiple transcription factors.", "multiple transcription factors. many", "transcription factors. many mk", "factors. many mk specific", "many mk specific genes", "mk specific genes are", "specific genes are co", "genes are co regulated", "are co regulated by", "co regulated by gata", "regulated by gata and", "by gata and friend", "gata and friend of", "and friend of gata", "of gata fog", "fog runx1", "runx1 and ets proteins.", "and ets proteins. nuclear", "ets proteins. nuclear factor", "proteins. nuclear factor erythroid", "nuclear factor erythroid 2", "erythroid 2 nf", "2 nf e2", "e2 which", "which has an mk", "has an mk erythroid", "an mk erythroid specific", "mk erythroid specific 45", "erythroid specific 45 kda", "specific 45 kda subunit", "kda subunit controls", "subunit controls terminal", "controls terminal mk maturation", "mk maturation proplatelet", "maturation proplatelet formation", "proplatelet formation and platelet", "formation and platelet release", "platelet release schulze", "release schulze &", "schulze & shivdasani 2004", "& shivdasani 2004 .", "shivdasani 2004 . nf", "2004 . nf e2", ". nf e2 deficient", "nf e2 deficient mice", "e2 deficient mice have", "deficient mice have profound", "mice have profound thrombocytopenia", "profound thrombocytopenia shiraga", "thrombocytopenia shiraga et", "shiraga et al. 1999", "et al. 1999 .", "al. 1999 . myb", ". myb c", "myb c myb", "c myb functions", "myb functions with", "with ep300 p300", "p300 as a", "as a negative regulator", "a negative regulator of", "negative regulator of thrombopoiesis", "of thrombopoiesis metcalf", "thrombopoiesis metcalf et", "metcalf et al. 2005", "et al. 2005 .", "al. 2005 . during", "2005 . during mk", ". during mk maturation", "mk maturation internal", "maturation internal membrane", "membrane systems granules", "systems granules and", "granules and organelles are", "and organelles are assembled.", "organelles are assembled. cytoplasmic", "are assembled. cytoplasmic fragmentation", "assembled. cytoplasmic fragmentation requires", "cytoplasmic fragmentation requires changes", "fragmentation requires changes in", "requires changes in the", "changes in the mk", "in the mk cytoskeleton", "the mk cytoskeleton and", "mk cytoskeleton and formation", "cytoskeleton and formation of", "and formation of organelles", "formation of organelles and", "of organelles and channels.", "organelles and channels. individual", "and channels. individual organelles", "channels. individual organelles migrate", "individual organelles migrate from", "organelles migrate from the", "migrate from the cell", "from the cell body", "the cell body to", "cell body to the", "body to the proplatelet", "to the proplatelet ends", "proplatelet ends with", "ends with approximately", "with approximately 30 percent", "approximately 30 percent of", "30 percent of organelles/granules", "percent of organelles/granules in", "of organelles/granules in motion", "organelles/granules in motion at", "in motion at any", "motion at any given", "at any given time", "given time richardson", "time richardson et", "richardson et al. 2005", "megakaryocytes mks give", "mks give rise to", "give rise to circulating platelets", "to circulating platelets thrombocytes", "platelets thrombocytes through", "thrombocytes through terminal differentiation", "through terminal differentiation of mks", "terminal differentiation of mks which", "differentiation of mks which release", "of mks which release cytoplasmic", "mks which release cytoplasmic fragments", "which release cytoplasmic fragments as", "release cytoplasmic fragments as circulating", "cytoplasmic fragments as circulating platelets.", "fragments as circulating platelets. as", "as circulating platelets. as mks", "circulating platelets. as mks mature", "platelets. as mks mature they", "as mks mature they undergo", "mks mature they undergo endoreduplication", "they undergo endoreduplication polyploidisation", "endoreduplication polyploidisation and", "polyploidisation and expansion of", "and expansion of cytoplasmic mass", "expansion of cytoplasmic mass to", "of cytoplasmic mass to cell", "cytoplasmic mass to cell sizes", "mass to cell sizes larger", "to cell sizes larger than", "cell sizes larger than 50", "sizes larger than 50 100", "larger than 50 100 microns", "50 100 microns and", "100 microns and ploidy", "microns and ploidy ranges", "and ploidy ranges up to", "ploidy ranges up to 128", "ranges up to 128 n.", "up to 128 n. as", "to 128 n. as mks", "128 n. as mks mature", "as mks mature the", "mks mature the polyploid", "mature the polyploid nucleus", "the polyploid nucleus becomes horseshoe", "polyploid nucleus becomes horseshoe shaped", "becomes horseshoe shaped the", "horseshoe shaped the cytoplasm", "shaped the cytoplasm expands", "the cytoplasm expands and", "cytoplasm expands and platelet", "expands and platelet organelles", "and platelet organelles and the", "platelet organelles and the demarcation", "organelles and the demarcation membrane", "and the demarcation membrane system", "the demarcation membrane system are", "demarcation membrane system are amplified.", "membrane system are amplified. proplatelet", "system are amplified. proplatelet projections", "are amplified. proplatelet projections form", "amplified. proplatelet projections form which", "proplatelet projections form which give", "projections form which give rise", "form which give rise to", "which give rise to de", "give rise to de novo", "rise to de novo circulating", "to de novo circulating platelets", "novo circulating platelets deutsch", "circulating platelets deutsch &", "platelets deutsch & tomer", "deutsch & tomer 2006 .", "tomer 2006 .
the", "2006 .
the processes", ".
the processes of", "
the processes of megakaryocytopoiesis and", "processes of megakaryocytopoiesis and platelet", "of megakaryocytopoiesis and platelet production", "megakaryocytopoiesis and platelet production occur", "and platelet production occur within", "platelet production occur within a", "production occur within a complex", "occur within a complex microenvironment", "within a complex microenvironment where", "a complex microenvironment where chemokines", "microenvironment where chemokines cytokines", "where chemokines cytokines and", "chemokines cytokines and adhesive", "cytokines and adhesive interactions play", "and adhesive interactions play major", "adhesive interactions play major roles", "play major roles avecilla", "major roles avecilla et", "roles avecilla et al.", "avecilla et al. 2004 .", "et al. 2004 . megakaryocytopoiesis", "al. 2004 . megakaryocytopoiesis is", "2004 . megakaryocytopoiesis is regulated", ". megakaryocytopoiesis is regulated at", "megakaryocytopoiesis is regulated at several", "is regulated at several levels", "regulated at several levels including", "at several levels including proliferation", "levels including proliferation differentiation", "including proliferation differentiation and", "proliferation differentiation and platelet", "and platelet release kaushansky", "platelet release kaushansky 2003", "release kaushansky 2003 .", "2003 . thrombopoietin tpo/c", ". thrombopoietin tpo/c mpl", "thrombopoietin tpo/c mpl ligand", "tpo/c mpl ligand is", "mpl ligand is the", "ligand is the most", "is the most potent cytokine", "the most potent cytokine stimulating", "most potent cytokine stimulating proliferation", "potent cytokine stimulating proliferation and", "cytokine stimulating proliferation and maturation", "stimulating proliferation and maturation of", "proliferation and maturation of mk", "and maturation of mk progenitors", "of mk progenitors kaushansky", "mk progenitors kaushansky 2005", "kaushansky 2005 but many", "2005 but many other", "but 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"profound thrombocytopenia shiraga et", "thrombocytopenia shiraga et al.", "shiraga et al. 1999 .", "et al. 1999 . myb", "1999 . myb c", ". myb c myb", "c myb functions with", "myb functions with ep300", "functions with ep300 p300", "ep300 p300 as", "p300 as a negative", "as a negative regulator of", "a negative regulator of thrombopoiesis", "regulator of thrombopoiesis metcalf", "of thrombopoiesis metcalf et", "thrombopoiesis metcalf et al.", "metcalf et al. 2005 .", "et al. 2005 . during", "al. 2005 . during mk", "2005 . during mk maturation", "during mk maturation internal", "mk maturation internal membrane", "maturation internal membrane systems", "internal membrane systems granules", "membrane systems granules and", "systems granules and organelles", "granules and organelles are assembled.", "and organelles are assembled. cytoplasmic", "organelles are assembled. cytoplasmic fragmentation", "are assembled. cytoplasmic fragmentation requires", "assembled. cytoplasmic fragmentation 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activated", "2010 .
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phosphorylated", "other kinases.
phosphorylated bcap", "kinases.
phosphorylated bcap recruits", "bcap recruits pi3k", "pi3k which", "which is phosphorylated", "is phosphorylated by", "phosphorylated by a", "by a syk", "a syk dependent", "syk dependent mechanism", "mechanism kuwahara", "kuwahara et al.", "et al. 1996", "1996 and", "and produces phosphatidylinositol", "produces phosphatidylinositol 3", "phosphatidylinositol 3 4", "3 4 5", "4 5 trisphosphate", "trisphosphate pip3", "pip3 . phosphorylated", ". phosphorylated cd19", "phosphorylated cd19 likewise", "cd19 likewise recruits", "likewise recruits pip3k.", "recruits pip3k. pip3", "pip3k. pip3 recruits", "pip3 recruits bam32", "bam32 marshall", "marshall et al.", "et al. 2000", "2000 and", "btk de", "de weers et", "weers et al.", "1994 baba", "baba et al.", "et al. 2001", "2001 to", "plasma membrane via", "membrane via their", "via their ph", "their ph domains.", "ph domains. pip3", "domains. pip3 also", "pip3 also recruits", "also recruits and", "recruits and activates", "and activates plc", "activates plc gamma1", "plc gamma1 and", "gamma1 and plc", "and plc gamma2", "gamma2 bae", "bae et al.", "et al. 1998", "al. 1998 .", "1998 . btk", ". btk binds", "btk binds phosphorylated", "binds phosphorylated blnk", "phosphorylated blnk via", "blnk via its", "via its sh2", "its sh2 domain", "domain baba", "al. 2001 .", "2001 . btk", ". btk phosphorylates", "btk phosphorylates plc", "phosphorylates plc gamma2", "gamma2 rodriguez", "rodriguez et al.", "which activates phospholipase", "activates phospholipase activity", "activity carter", "carter et al.", "1991 roifman", "roifman and wang", "and wang 1992", "1992 kim", "kim et al.", "et al. 2004", "2004 sekiya", "sekiya et al.", "al. 2004 .", "2004 . phosphorylated", ". phosphorylated blnk", "phosphorylated blnk recruits", "blnk recruits plc", "recruits plc gamma", "gamma vav", "vav grb2", "grb2 and", "nck fu", "fu and chan", "and chan 1997", "1997 fu", "1998 chiu", "chiu et al.", "et al. 2002", "al. 2002 .
plc", "2002 .
plc gamma", ".
plc gamma hydrolyzes", "gamma hydrolyzes phosphatidylinositol", "hydrolyzes phosphatidylinositol 4", "phosphatidylinositol 4 5", "4 5 bisphosphate", "5 bisphosphate to", "bisphosphate to yield", "to yield inositol", "yield inositol 1", "inositol 1 4", "1 4 5", "trisphosphate ip3", "ip3 and", "diacylglycerol carter", "1991 kim", "2004 . ip3", ". ip3 binds", "ip3 binds receptors", "binds receptors on", "receptors on the", "on the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum and", "reticulum and causes", "and causes release", "causes release of", "release of ca2+", "of ca2+ ions", "ca2+ ions from", "ions from the", "from the er", "the er into", "er into the", "into the cytosol.", "the cytosol. the", "cytosol. the depletion", "the depletion of", "depletion of calcium", "of calcium from", "calcium from the", "the er in", "er in turn", "in turn activates", "turn activates stim1", "activates stim1 to", "stim1 to interact", "to interact with", "interact with orai", "with orai and", "orai and trpc1", "and trpc1 channels", "channels and", "and possibly other", "possibly other trp", "other trp channels", "channels in", "in the plasma", "membrane resulting", "resulting in an", "in an influx", "an influx of", "influx of extracellular", "of extracellular calcium", "extracellular calcium ions", "ions mori", "mori et al.", "2002 muik", "muik et al.", "2008 luik", "luik et al.", "2008 park", "park et al.", "et al. 2009", "al. 2009 .", "mature b cells express", "b cells express igm", "cells express igm and", "express igm and igd", "igm and igd immunoglobulins", "and igd immunoglobulins which", "igd immunoglobulins which are", "immunoglobulins which are complexed", "which are complexed with", "are complexed with ig", "complexed with ig alpha", "ig alpha cd79a", "cd79a mb 1", "mb 1 and", "1 and ig", "ig beta cd79b", "b29 to form", "to form the b", "form the b cell", "the b cell receptor", "bcr fu", "fu et al. 1974", "al. 1974 fu", "1974 fu et", "fu et al. 1975", "al. 1975 kunkel", "1975 kunkel et", "kunkel et al. 1975", "al. 1975 van", "1975 van noesal", "van noesal et al.", "noesal et al. 1992", "al. 1992 sanchez", "1992 sanchez et", "sanchez et al. 1993", "al. 1993 reviewed", "1993 reviewed in", "reviewed in brezski and", "in brezski and monroe", "brezski and monroe 2008", "and monroe 2008 .", "monroe 2008 . binding", "2008 . binding of", ". binding of antigen", "binding of antigen to", "of antigen to the", "antigen to the immunoglobulin", "to the immunoglobulin activates", "the immunoglobulin activates phosphorylation", "immunoglobulin activates phosphorylation of", "activates phosphorylation of immunoreceptor", "phosphorylation of immunoreceptor tyrosine", "of immunoreceptor tyrosine based", "immunoreceptor tyrosine based activation", "tyrosine based activation motifs", "activation motifs itams", "itams in the", "in the cytoplasmic tails", "the cytoplasmic tails of", "cytoplasmic tails of ig", "tails of ig alpha", "of ig alpha and", "ig alpha and ig", "alpha and ig beta", "and ig beta by", "ig beta by src", "beta by src family", "by src family tyrosine", "src family tyrosine kinases", "tyrosine kinases including", "kinases including lyn", "including lyn fyn", "fyn and blk", "and blk nel", "blk nel et", "nel et al. 1984", "al. 1984 yamanashi", "1984 yamanashi et", "yamanashi et al. 1991", "al. 1991 flaswinkel", "1991 flaswinkel and", "flaswinkel and reth 1994", "reth 1994 saouaf", "1994 saouaf et", "saouaf et al. 1994", "al. 1994 hata", "1994 hata et", "hata et al. 1994", "al. 1994 saouaf", "saouaf et al. 1995", "al. 1995 reviewed", "1995 reviewed in", "reviewed in gauld and", "in gauld and cambier", "gauld and cambier 2004", "cambier 2004 reviewed", "2004 reviewed in", "reviewed in harwood and", "in harwood and batista", "harwood and batista 2010", "and batista 2010 .", "batista 2010 . the", "2010 . the protein", ". the protein kinase", "the protein kinase syk", "protein kinase syk may", "kinase syk may also", "syk may also be", "may also be involved", "also be involved in", "be involved in phosphorylating", "involved in phosphorylating the", "in phosphorylating the itams.
the", "phosphorylating the itams.
the protein", "the itams.
the protein kinase", "itams.
the protein kinase syk", "protein kinase syk binds", "kinase syk binds the", "syk binds the phosphorylated", "binds the phosphorylated immunoreceptor", "the phosphorylated immunoreceptor tyrosine", "phosphorylated immunoreceptor tyrosine activated", "immunoreceptor tyrosine activated motifs", "activated motifs itams", "itams on the", "on the cytoplasmic tails", "b29 wienands", "wienands et al. 1995", "al. 1995 rowley", "1995 rowley et", "rowley et al. 1995", "al. 1995 tsang", "1995 tsang et", "tsang et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the binding", ". the binding causes", "the binding causes the", "binding causes the activation", "causes the activation and", "the activation and autophosphorylation", "activation and autophosphorylation of", "and autophosphorylation of syk", "of syk law", "syk law et", "law et al. 1994", "al. 1994 irish", "1994 irish et", "irish et al. 2006", "al. 2006 baldock", "2006 baldock et", "baldock et al. 2008", "al. 2008 tsang", "2008 tsang et", "al. 2008 reviewed", "2008 reviewed in", "reviewed in bradshaw 2010", "in bradshaw 2010 .
activated", "bradshaw 2010 .
activated syk", "2010 .
activated syk and", ".
activated syk and other", "syk and other kinases", "and other kinases phosphorylate", "other kinases phosphorylate blnk", "phosphorylate blnk slp", "blnk slp 65", "slp 65 bash", "bash and bcap.", "and bcap. lyn", "bcap. lyn and", "lyn and fyn phosphorylate", "and fyn phosphorylate cd19.", "fyn phosphorylate cd19. phosphorylated", "phosphorylate cd19. phosphorylated blnk", "phosphorylated blnk bcap", "and cd19 serve as", "cd19 serve as scaffolds", "serve as scaffolds which", "as scaffolds which recruit", "scaffolds which recruit effectors", "which recruit effectors to", "recruit effectors to the", "effectors to the plasma", "to the plasma membrane", "the plasma membrane and", "plasma membrane and assemble", "membrane and assemble large", "and assemble large complexes", "large complexes the", "complexes the signalosomes.", "the signalosomes. bcap", "signalosomes. bcap and", "bcap and cd19 recruit", "and cd19 recruit phosphoinositol", "cd19 recruit phosphoinositol 3", "recruit phosphoinositol 3 kinase", "3 kinase pi3k", "kinase pi3k .", "pi3k . blnk recruits", ". blnk recruits phospholipase", "blnk recruits phospholipase c", "recruits phospholipase c gamma", "c gamma predominantly", "gamma predominantly plc", "predominantly plc gamma2 in", "plc gamma2 in b", "gamma2 in b cells", "b cells coggeshall", "cells coggeshall et", "coggeshall et al. 1992", "1992 nck", "vav1 and shc.", "and shc. the effectors", "shc. the effectors are", "the effectors are phosphorylated", "effectors are phosphorylated by", "are phosphorylated by syk", "phosphorylated by syk and", "by syk and other", "syk and other kinases.
phosphorylated", "and other kinases.
phosphorylated bcap", "other kinases.
phosphorylated bcap recruits", "kinases.
phosphorylated bcap recruits pi3k", "recruits pi3k which", "pi3k which is", "which is phosphorylated by", "is phosphorylated by a", "phosphorylated by a syk", "by a syk dependent", "a syk dependent mechanism", "dependent mechanism kuwahara", "mechanism kuwahara et", "kuwahara et al. 1996", "al. 1996 and", "1996 and produces", "and produces phosphatidylinositol 3", "produces phosphatidylinositol 3 4", "phosphatidylinositol 3 4 5", "3 4 5 trisphosphate", "5 trisphosphate pip3", "trisphosphate pip3 .", "pip3 . phosphorylated cd19", ". phosphorylated cd19 likewise", "phosphorylated cd19 likewise recruits", "cd19 likewise recruits pip3k.", "likewise recruits pip3k. pip3", "recruits pip3k. pip3 recruits", "pip3k. pip3 recruits bam32", "recruits bam32 marshall", "bam32 marshall et", "marshall et al. 2000", "al. 2000 and", "2000 and btk", "and btk de", "btk de weers", "de weers et al.", "weers et al. 1994", "al. 1994 baba", "1994 baba et", "baba et al. 2001", "al. 2001 to", "2001 to the", "the plasma membrane via", "plasma membrane via their", "membrane via their ph", "via their ph domains.", "their ph domains. pip3", "ph domains. pip3 also", "domains. pip3 also recruits", "pip3 also recruits and", "also recruits and activates", "recruits and activates plc", "and activates plc gamma1", "activates plc gamma1 and", "plc gamma1 and plc", "gamma1 and plc gamma2", "plc gamma2 bae", "gamma2 bae et", "bae et al. 1998", "et al. 1998 .", "al. 1998 . btk", "1998 . btk binds", ". btk binds phosphorylated", "btk binds phosphorylated blnk", "binds phosphorylated blnk via", "phosphorylated blnk via its", "blnk via its sh2", "via its sh2 domain", "sh2 domain baba", "domain baba et", "et al. 2001 .", "al. 2001 . btk", "2001 . btk phosphorylates", ". btk phosphorylates plc", "btk phosphorylates plc gamma2", "plc gamma2 rodriguez", "gamma2 rodriguez et", "rodriguez et al. 2001", "2001 which", "which activates phospholipase activity", "phospholipase activity carter", "activity carter et", "carter et al. 1991", "al. 1991 roifman", "1991 roifman and", "roifman and wang 1992", "wang 1992 kim", "1992 kim et", "kim et al. 2004", "al. 2004 sekiya", "2004 sekiya et", "sekiya et al. 2004", "et al. 2004 .", "al. 2004 . phosphorylated", "2004 . phosphorylated blnk", ". phosphorylated blnk recruits", "phosphorylated blnk recruits plc", "blnk recruits plc gamma", "plc gamma vav", "grb2 and nck", "and nck fu", "nck fu and", "fu and chan 1997", "chan 1997 fu", "1997 fu et", "fu et al. 1998", "al. 1998 chiu", "1998 chiu et", "chiu et al. 2002", "et al. 2002 .
plc", "al. 2002 .
plc gamma", "2002 .
plc gamma hydrolyzes", ".
plc gamma hydrolyzes phosphatidylinositol", "gamma hydrolyzes phosphatidylinositol 4", "hydrolyzes phosphatidylinositol 4 5", "phosphatidylinositol 4 5 bisphosphate", "4 5 bisphosphate to", "5 bisphosphate to yield", "bisphosphate to yield inositol", "to yield inositol 1", "yield inositol 1 4", "inositol 1 4 5", "1 4 5 trisphosphate", "5 trisphosphate ip3", "ip3 and diacylglycerol", "and diacylglycerol carter", "diacylglycerol carter et", "al. 1991 kim", "1991 kim et", "al. 2004 . ip3", "2004 . ip3 binds", ". ip3 binds receptors", "ip3 binds receptors on", "binds receptors on the", "receptors on the endoplasmic", "on the endoplasmic reticulum", "the endoplasmic reticulum and", "endoplasmic reticulum and causes", "reticulum and causes release", "and causes release of", "causes release of ca2+", "release of ca2+ ions", "of ca2+ ions from", "ca2+ ions from the", "ions from the er", "from the er into", "the er into the", "er into the cytosol.", "into the cytosol. the", "the cytosol. the depletion", "cytosol. the depletion of", "the depletion of calcium", "depletion of calcium from", "of calcium from the", "calcium from the er", "from the er in", "the er in turn", "er in turn activates", "in turn activates stim1", "turn activates stim1 to", "activates stim1 to interact", "stim1 to interact with", "to interact with orai", "interact with orai and", "with orai and trpc1", "orai and trpc1 channels", "trpc1 channels and", "channels and possibly", "and possibly other trp", "possibly other trp channels", "trp channels in", "channels in the", "in the plasma membrane", "plasma membrane resulting", "membrane resulting in", "resulting in an influx", "in an influx of", "an influx of extracellular", "influx of extracellular calcium", "of extracellular calcium ions", "calcium ions mori", "ions mori et", "mori et al. 2002", "al. 2002 muik", "2002 muik et", "muik et al. 2008", "al. 2008 luik", "2008 luik et", "luik et al. 2008", "al. 2008 park", "2008 park et", "park et al. 2009", "et al. 2009 .", "mature b cells express igm", "b cells express igm and", "cells express igm and igd", "express igm and igd immunoglobulins", "igm and igd immunoglobulins which", "and igd immunoglobulins which are", "igd immunoglobulins which are complexed", "immunoglobulins which are complexed with", "which are complexed with ig", "are complexed with ig alpha", "with ig alpha cd79a", "alpha cd79a mb", "mb 1 and ig", "1 and ig beta", "and ig beta cd79b", "beta cd79b b29", "cd79b b29 to", "b29 to form the", "to form the b cell", "form the b cell receptor", "bcr fu et", "et al. 1974 fu", "al. 1974 fu et", "1974 fu et al.", "et al. 1975 kunkel", "al. 1975 kunkel et", "1975 kunkel et al.", "et al. 1975 van", "al. 1975 van noesal", "1975 van noesal et", "van noesal et al. 1992", "et al. 1992 sanchez", "al. 1992 sanchez et", "1992 sanchez et al.", "et al. 1993 reviewed", "al. 1993 reviewed in", "1993 reviewed in brezski", "reviewed in brezski and monroe", "in brezski and monroe 2008", "brezski and monroe 2008 .", "and monroe 2008 . binding", "monroe 2008 . binding of", "2008 . binding of antigen", ". binding of antigen to", "binding of antigen to the", "of antigen to the immunoglobulin", "antigen to the immunoglobulin activates", "to the immunoglobulin activates phosphorylation", "the immunoglobulin activates phosphorylation of", "immunoglobulin activates phosphorylation of immunoreceptor", "activates phosphorylation of immunoreceptor tyrosine", "phosphorylation of immunoreceptor tyrosine based", "of immunoreceptor tyrosine based activation", "immunoreceptor tyrosine based activation motifs", "based activation motifs itams", "motifs itams in", "itams in the cytoplasmic", "in the cytoplasmic tails of", "the cytoplasmic tails of ig", "cytoplasmic tails of ig alpha", "tails of ig alpha and", "of ig alpha and ig", "ig alpha and ig beta", "alpha and ig beta by", "and ig beta by src", "ig beta by src family", "beta by src family tyrosine", "by src family tyrosine kinases", "family tyrosine kinases including", "tyrosine kinases including lyn", "lyn fyn and", "and blk nel et", "blk nel et al.", "et al. 1984 yamanashi", "al. 1984 yamanashi et", "1984 yamanashi et al.", "et al. 1991 flaswinkel", "al. 1991 flaswinkel and", "1991 flaswinkel and reth", "and reth 1994 saouaf", "reth 1994 saouaf et", "1994 saouaf et al.", "et al. 1994 hata", "al. 1994 hata et", "1994 hata et al.", "et al. 1994 saouaf", "al. 1994 saouaf et", "et al. 1995 reviewed", "al. 1995 reviewed in", "1995 reviewed in gauld", "reviewed in gauld and cambier", "in gauld and cambier 2004", "and cambier 2004 reviewed", "cambier 2004 reviewed in", "2004 reviewed in harwood", "reviewed in harwood and batista", "in harwood and batista 2010", "harwood and batista 2010 .", "and batista 2010 . the", "batista 2010 . the protein", "2010 . the protein kinase", ". the protein kinase syk", "the protein kinase syk may", "protein kinase syk may also", "kinase syk may also be", "syk may also be involved", "may also be involved in", "also be involved in phosphorylating", "be involved in phosphorylating the", "involved in phosphorylating the itams.
the", "in phosphorylating the itams.
the protein", "phosphorylating the itams.
the protein kinase", "the itams.
the protein kinase syk", "itams.
the protein kinase syk binds", "protein kinase syk binds the", "kinase syk binds the phosphorylated", "syk binds the phosphorylated immunoreceptor", "binds the phosphorylated immunoreceptor tyrosine", "the phosphorylated immunoreceptor tyrosine activated", "phosphorylated immunoreceptor tyrosine activated motifs", "tyrosine activated motifs itams", "motifs itams on", "itams on the cytoplasmic", "on the cytoplasmic tails of", "of ig alpha cd79a", "b29 wienands et", "et al. 1995 rowley", "al. 1995 rowley et", "1995 rowley et al.", "et al. 1995 tsang", "al. 1995 tsang et", "1995 tsang et al.", "tsang et al. 2008 .", "et al. 2008 . the", "al. 2008 . the binding", "2008 . the binding causes", ". the binding causes the", "the binding causes the activation", "binding causes the activation and", "causes the activation and autophosphorylation", "the activation and autophosphorylation of", "activation and autophosphorylation of syk", "autophosphorylation of syk law", "of syk law et", "syk law et al.", "et al. 1994 irish", "al. 1994 irish et", "1994 irish et al.", "et al. 2006 baldock", "al. 2006 baldock et", "2006 baldock et al.", "et al. 2008 tsang", "al. 2008 tsang et", "2008 tsang et al.", "et al. 2008 reviewed", "al. 2008 reviewed in", "2008 reviewed in bradshaw", "reviewed in bradshaw 2010 .
activated", "in bradshaw 2010 .
activated syk", "bradshaw 2010 .
activated syk and", "2010 .
activated syk and other", ".
activated syk and other kinases", "syk and other kinases phosphorylate", "and other kinases phosphorylate blnk", "kinases phosphorylate blnk slp", "phosphorylate blnk slp 65", "65 bash and", "and bcap. lyn and", "bcap. lyn and fyn", "lyn and fyn phosphorylate cd19.", "and fyn phosphorylate cd19. phosphorylated", "fyn phosphorylate cd19. phosphorylated blnk", "cd19. phosphorylated blnk bcap", "blnk bcap and", "bcap and cd19 serve", "and cd19 serve as scaffolds", "cd19 serve as scaffolds which", "serve as scaffolds which recruit", "as scaffolds which recruit effectors", "scaffolds which recruit effectors to", "which recruit effectors to the", "recruit effectors to the plasma", "effectors to the plasma membrane", "to the plasma membrane and", "the plasma membrane and assemble", "plasma membrane and assemble large", "membrane and assemble large complexes", "assemble large complexes the", "large complexes the signalosomes.", "the signalosomes. bcap and", "signalosomes. bcap and cd19", "bcap and cd19 recruit phosphoinositol", "and cd19 recruit phosphoinositol 3", "cd19 recruit phosphoinositol 3 kinase", "phosphoinositol 3 kinase pi3k", "3 kinase pi3k .", "kinase pi3k . blnk", "pi3k . blnk recruits phospholipase", ". blnk recruits phospholipase c", "blnk recruits phospholipase c gamma", "phospholipase c gamma predominantly", "c gamma predominantly plc", "gamma predominantly plc gamma2", "predominantly plc gamma2 in b", "plc gamma2 in b cells", "in b cells coggeshall", "b cells coggeshall et", "cells coggeshall et al.", "al. 1992 nck", "nck bam32 btk", "bam32 btk vav1", "btk vav1 and", "vav1 and shc. the", "and shc. the effectors are", "shc. the effectors are phosphorylated", "the effectors are phosphorylated by", "effectors are phosphorylated by syk", "are phosphorylated by syk and", "phosphorylated by syk and other", "by syk and other kinases.
phosphorylated", "syk and other kinases.
phosphorylated bcap", "and other kinases.
phosphorylated bcap recruits", "other kinases.
phosphorylated bcap recruits pi3k", "bcap recruits pi3k which", "recruits pi3k which is", "pi3k which is phosphorylated", "which is phosphorylated by a", "is phosphorylated by a syk", "phosphorylated by a syk dependent", "by a syk dependent mechanism", "syk dependent mechanism kuwahara", "dependent mechanism kuwahara et", "mechanism kuwahara et al.", "et al. 1996 and", "al. 1996 and produces", "1996 and produces phosphatidylinositol", "and produces phosphatidylinositol 3 4", "produces phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "4 5 trisphosphate pip3", "5 trisphosphate pip3 .", "trisphosphate pip3 . phosphorylated", "pip3 . phosphorylated cd19 likewise", ". phosphorylated cd19 likewise recruits", "phosphorylated cd19 likewise recruits pip3k.", "cd19 likewise recruits pip3k. pip3", "likewise recruits pip3k. pip3 recruits", "recruits pip3k. pip3 recruits bam32", "pip3 recruits bam32 marshall", "recruits bam32 marshall et", "bam32 marshall et al.", "et al. 2000 and", "al. 2000 and btk", "and btk de weers", "btk de weers et", "de weers et al. 1994", "et al. 1994 baba", "al. 1994 baba et", "1994 baba et al.", "et al. 2001 to", "al. 2001 to the", "2001 to the plasma", "to the plasma membrane via", "the plasma membrane via their", "plasma membrane via their ph", "membrane via their ph domains.", "via their ph domains. pip3", "their ph domains. pip3 also", "ph domains. pip3 also recruits", "domains. pip3 also recruits and", "pip3 also recruits and activates", "also recruits and activates plc", "recruits and activates plc gamma1", "and activates plc gamma1 and", "activates plc gamma1 and plc", "plc gamma1 and plc gamma2", "and plc gamma2 bae", "plc gamma2 bae et", "gamma2 bae et al.", "bae et al. 1998 .", "et al. 1998 . btk", "al. 1998 . btk binds", "1998 . btk binds phosphorylated", ". btk binds phosphorylated blnk", "btk binds phosphorylated blnk via", "binds phosphorylated blnk via its", "phosphorylated blnk via its sh2", "blnk via its sh2 domain", "its sh2 domain baba", "sh2 domain baba et", "domain baba et al.", "baba et al. 2001 .", "et al. 2001 . btk", "al. 2001 . btk phosphorylates", "2001 . btk phosphorylates plc", ". btk phosphorylates plc gamma2", "phosphorylates plc gamma2 rodriguez", "plc gamma2 rodriguez et", "gamma2 rodriguez et al.", "al. 2001 which", "2001 which activates", "activates phospholipase activity carter", "phospholipase activity carter et", "activity carter et al.", "et al. 1991 roifman", "al. 1991 roifman and", "1991 roifman and wang", "and wang 1992 kim", "wang 1992 kim et", "1992 kim et al.", "et al. 2004 sekiya", "al. 2004 sekiya et", "2004 sekiya et al.", "sekiya et al. 2004 .", "et al. 2004 . phosphorylated", "al. 2004 . phosphorylated blnk", "2004 . phosphorylated blnk recruits", ". phosphorylated blnk recruits plc", "phosphorylated blnk recruits plc gamma", "recruits plc gamma vav", "gamma vav grb2", "vav grb2 and", "and nck fu and", "nck fu and chan", "and chan 1997 fu", "chan 1997 fu et", "1997 fu et al.", "et al. 1998 chiu", "al. 1998 chiu et", "1998 chiu et al.", "chiu et al. 2002 .
plc", "et al. 2002 .
plc gamma", "al. 2002 .
plc gamma hydrolyzes", "2002 .
plc gamma hydrolyzes phosphatidylinositol", ".
plc gamma hydrolyzes phosphatidylinositol 4", "gamma hydrolyzes phosphatidylinositol 4 5", "hydrolyzes phosphatidylinositol 4 5 bisphosphate", "phosphatidylinositol 4 5 bisphosphate to", "4 5 bisphosphate to yield", "5 bisphosphate to yield inositol", "bisphosphate to yield inositol 1", "to yield inositol 1 4", "yield inositol 1 4 5", "inositol 1 4 5 trisphosphate", "4 5 trisphosphate ip3", "trisphosphate ip3 and", "and diacylglycerol carter et", "diacylglycerol carter et al.", "et al. 1991 kim", "al. 1991 kim et", "1991 kim et al.", "kim et al. 2004 .", "et al. 2004 . ip3", "al. 2004 . ip3 binds", "2004 . ip3 binds receptors", ". ip3 binds receptors on", "ip3 binds receptors on the", "binds receptors on the endoplasmic", "receptors on the endoplasmic reticulum", "on the endoplasmic reticulum and", "the endoplasmic reticulum and causes", "endoplasmic reticulum and causes release", "reticulum and causes release of", "and causes release of ca2+", "causes release of ca2+ ions", "release of ca2+ ions from", "of ca2+ ions from the", "ca2+ ions from the er", "ions from the er into", "from the er into the", "the er into the cytosol.", "er into the cytosol. the", "into the cytosol. the depletion", "the cytosol. the depletion of", "cytosol. the depletion of calcium", "the depletion of calcium from", "depletion of calcium from the", "of calcium from the er", "calcium from the er in", "from the er in turn", "the er in turn activates", "er in turn activates stim1", "in turn activates stim1 to", "turn activates stim1 to interact", "activates stim1 to interact with", "stim1 to interact with orai", "to interact with orai and", "interact with orai and trpc1", "with orai and trpc1 channels", "and trpc1 channels and", "trpc1 channels and possibly", "channels and possibly other", "and possibly other trp channels", "other trp channels in", "trp channels in the", "channels in the plasma", "the plasma membrane resulting", "plasma membrane resulting in", "membrane resulting in an", "resulting in an influx of", "in an influx of extracellular", "an influx of extracellular calcium", "influx of extracellular calcium ions", "extracellular calcium ions mori", "calcium ions mori et", "ions mori et al.", "et al. 2002 muik", "al. 2002 muik et", "2002 muik et al.", "et al. 2008 luik", "al. 2008 luik et", "2008 luik et al.", "et al. 2008 park", "al. 2008 park et", "2008 park et al.", "park et al. 2009 ." ] }, { "record_id": "GLY_000594_1_716", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "983712", "r hsa", "hsa 983712", "r hsa 983712" ] }, { "record_id": "GLY_000594_1_716", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ion channel", "channel transport", "ion channel transport", "ion channels", "channels mediate", "mediate the", "the flow", "flow of", "of ions", "ions across", "across the", "the plasma", "plasma membrane", "membrane of", "of cells.", "cells. they", "they are", 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membrane ghomashchi et", "membrane ghomashchi et al.", "et al. 2010 singer", "al. 2010 singer et", "2010 singer et al.", "et al. 2002 cao", "al. 2002 cao et", "2002 cao et al.", "et al. 2008 zhao", "al. 2008 zhao et", "2008 zhao et al.", "zhao et al. 2008 ." ] }, { "record_id": "GLY_000594_1_719", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1482801", "r hsa", "hsa 1482801", "r hsa 1482801" ] }, { "record_id": "GLY_000594_1_719", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acyl chain", "chain remodelling", "remodelling of", "of ps", "acyl chain remodelling", "chain remodelling of", "remodelling of ps", "acyl chain remodelling of", "chain remodelling of ps", "acyl chain remodelling of ps", "in the", "the acyl", "remodelling pathway", "lands cycle", "is hydrolysed", "hydrolysed by", "by phopholipases", "phopholipases and", "and subsequently", "subsequently reacylated", "reacylated by", "by 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"composition of glycerophospholipids", "of glycerophospholipids to", "glycerophospholipids to generate", "to generate diverse", "generate diverse molecules", "diverse molecules asymmetrically", "molecules asymmetrically distributed", "asymmetrically distributed in", "distributed in the", "in the cell", "the cell membrane", "membrane ghomashchi", "ghomashchi et al.", "et al. 2010", "2010 singer", "singer et al.", "et al. 2002", "2002 cao", "cao et al.", "et al. 2008", "2008 hishikawa", "hishikawa et al.", "al. 2008 .", "in the acyl chain", "the acyl chain remodelling", "acyl chain remodelling pathway", "remodelling pathway lands", "pathway lands cycle", "cycle phosphatidylserine", "ps is hydrolysed", "is hydrolysed by phopholipases", "hydrolysed by phopholipases and", "by phopholipases and subsequently", "phopholipases and subsequently reacylated", "and subsequently reacylated by", "subsequently reacylated by acyltransferases.", "reacylated by acyltransferases. these", "by 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asymmetrically", "generate diverse molecules asymmetrically distributed", "diverse molecules asymmetrically distributed in", "molecules asymmetrically distributed in the", "asymmetrically distributed in the cell", "distributed in the cell membrane", "the cell membrane ghomashchi", "cell membrane ghomashchi et", "membrane ghomashchi et al.", "et al. 2010 singer", "al. 2010 singer et", "2010 singer et al.", "et al. 2002 cao", "al. 2002 cao et", "2002 cao et al.", "et al. 2008 hishikawa", "al. 2008 hishikawa et", "2008 hishikawa et al.", "hishikawa et al. 2008 ." ] }, { "record_id": "GLY_000594_1_720", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1482839", "r hsa", "hsa 1482839", "r hsa 1482839" ] }, { "record_id": "GLY_000594_1_720", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acyl chain", "chain remodelling", "remodelling of", "of pe", "acyl chain remodelling", "chain remodelling of", 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"of cholesterol biosynthesis by srebp", "biosynthesis by srebp srebf", "sterol regulatory", "regulatory element", "element binding", "binding proteins", "respond to", "to low", "low cholesterol", "cholesterol concentrations", "concentrations by", "by transiting", "transiting to", "to the", "the nucleus", "nucleus and", "and activating", "activating genes", "genes involved", "involved in", "in cholesterol", "cholesterol and", "and lipid", "lipid biosynthesis", "reviewed in", "in brown", "brown and", "and goldstein", "goldstein 2009", "osborne and", "and espenshade", "espenshade 2009", "weber et", "et al.", "al. 2004", "2004 .
", ".
newly", "newly synthesized", "synthesized srebps", "srebps are", "are transmembrane", "transmembrane proteins", "proteins that", "that bind", "bind scap", "scap in", "in the", "the endoplasmic", "endoplasmic reticulum", "membrane. scap", "scap binds", "binds cholesterol", "cholesterol which", "which causes", "causes a", "a conformational", "conformational change", "change that", "that allows", "allows scap", "scap to", "to interact", "interact with", "with insig", "retaining the", "the scap:srebp", "scap:srebp complex", "complex in", "the er.", "er. insig", "insig binds", "binds oxysterols", "which cause", "cause insig", "insig to", "to bind", "scap and", "and retain", "retain scap:srebp", "scap:srebp in", "endoplasmic reticulum.
in", "reticulum.
in low", "below about", "about 5", "5 mol%", "scap no", "no longer", "longer interacts", "interacts with", "with cholesterol", "cholesterol or", "or insig", "insig and", "and binds", "binds sec24", "sec24 of", "of the", "the copii", "copii coat", "coat complex", "complex instead.", "instead. thus", "thus scap:srebp", "scap:srebp transits", "transits with", "with the", "copii complex", "complex from", "from the", "the er", "er to", "the golgi.", "golgi. in", "the golgi", "golgi srebp", "srebp is", "is cleaved", "cleaved by", "by s1p", "s1p and", "and then", "then by", "by s2p", "releasing the", "the n", "n terminal", "terminal fragment", "fragment of", "of srebp", "srebp into", "into the", "the cytosol.", "cytosol. the", "fragment is", "is imported", "imported to", "nucleus by", "by importin", "importin beta", "beta and", "then acts", "acts with", "with other", "other factors", "such as", "as sp1", "sp1 and", "and nf", "nf y", "to activate", "activate transcription", "transcription of", "of target", "target genes.", "genes. targets", "targets of", "srebp include", "include the", "the genes", "genes encoding", "encoding all", "all enzymes", "enzymes of", "biosynthesis and", "and several", "several genes", "in lipogenesis.", "lipogenesis. srebp2", "srebp2 most", "most strongly", "strongly activates", "activates cholesterol", "biosynthesis while", "while srebp1c", "srebp1c most", "activates lipogenesis.", "sterol regulatory element", "regulatory element binding", "element binding proteins", "proteins srebps", "srebps srebfs", "srebfs respond", "respond to low", "to low cholesterol", "low cholesterol concentrations", "cholesterol concentrations by", "concentrations by transiting", "by transiting to", "transiting to the", "to the nucleus", "the nucleus and", "nucleus and activating", "and activating genes", "activating genes involved", "genes involved in", "involved in cholesterol", "in cholesterol and", "cholesterol and lipid", "and lipid biosynthesis", "biosynthesis reviewed", "reviewed in brown", "in brown and", "brown and goldstein", "and goldstein 2009", "2009 osborne", "osborne and espenshade", "and espenshade 2009", "2009 weber", "weber et al.", "et al. 2004", "al. 2004 .
", "2004 .
newly", ".
newly synthesized", "newly synthesized srebps", "synthesized srebps are", "srebps are transmembrane", "are transmembrane proteins", "transmembrane proteins that", "proteins that bind", "that bind scap", "bind scap in", "scap in the", "in the endoplasmic", "the endoplasmic reticulum", "reticulum er", "er membrane.", "membrane. scap binds", "scap binds cholesterol", "binds cholesterol which", "cholesterol which causes", "which causes a", "causes a conformational", "a conformational change", "conformational change that", "change that allows", "that allows scap", "allows scap to", "scap to interact", "to interact with", "interact with insig", "insig retaining", "retaining the scap:srebp", "the scap:srebp complex", "scap:srebp complex in", "complex in the", "in the er.", "the er. insig", "er. insig binds", "insig binds oxysterols", "oxysterols which", "which cause insig", "cause insig to", "insig to bind", "to bind scap", "bind scap and", "scap and retain", "and retain scap:srebp", "retain scap:srebp in", "scap:srebp in the", "the endoplasmic reticulum.
in", "endoplasmic reticulum.
in low", "reticulum.
in low cholesterol", "cholesterol below", "below about 5", "about 5 mol%", "mol% scap", "scap no longer", "no longer interacts", "longer interacts with", "interacts with cholesterol", "with cholesterol or", "cholesterol or insig", "or insig and", "insig and binds", "and binds sec24", "binds sec24 of", "sec24 of the", "of the copii", "the copii coat", "copii coat complex", "coat complex instead.", "complex instead. thus", "instead. thus scap:srebp", "thus scap:srebp transits", "scap:srebp transits with", "transits with the", "with the copii", "the copii complex", "copii complex from", "complex from the", "from the er", "the er to", "er to the", "to the golgi.", "the golgi. in", "golgi. in the", "in the golgi", "the golgi srebp", "golgi srebp is", "srebp is cleaved", "is cleaved by", "cleaved by s1p", "by s1p and", "s1p and then", "and then by", "then by s2p", "s2p releasing", "releasing the n", "the n terminal", "n terminal fragment", "terminal fragment of", "fragment of srebp", "of srebp into", "srebp into the", "into the cytosol.", "the cytosol. the", "cytosol. the n", "terminal fragment is", "fragment is imported", "is imported to", "imported to the", "the nucleus by", "nucleus by importin", "by importin beta", "importin beta and", "beta and then", "and then acts", "then acts with", "acts with other", "with other factors", "factors such", "such as sp1", "as sp1 and", "sp1 and nf", "and nf y", "y to", "to activate transcription", "activate transcription of", "transcription of target", "of target genes.", "target genes. targets", "genes. targets of", "targets of srebp", "of srebp include", "srebp include the", "include the genes", "the genes encoding", "genes encoding all", "encoding all enzymes", "all enzymes of", "enzymes of cholesterol", "cholesterol biosynthesis and", "biosynthesis and several", "and several genes", "several genes involved", "involved in lipogenesis.", "in lipogenesis. srebp2", "lipogenesis. srebp2 most", "srebp2 most strongly", "most strongly activates", "strongly activates cholesterol", "activates cholesterol biosynthesis", "cholesterol biosynthesis while", "biosynthesis while srebp1c", "while srebp1c most", "srebp1c most strongly", "strongly activates lipogenesis.", "sterol regulatory element binding", "regulatory element binding proteins", "binding proteins srebps", "srebfs respond to", "respond to low cholesterol", "to low cholesterol concentrations", "low cholesterol concentrations by", "cholesterol concentrations by transiting", "concentrations by transiting to", "by transiting to the", "transiting to the nucleus", "to the nucleus and", "the nucleus and activating", "nucleus and activating genes", "and activating genes involved", "activating genes involved in", "genes involved in cholesterol", "involved in cholesterol and", "in cholesterol and lipid", "cholesterol and lipid biosynthesis", "lipid biosynthesis reviewed", "biosynthesis reviewed in", "reviewed in brown and", "in brown and goldstein", "brown and goldstein 2009", "goldstein 2009 osborne", "2009 osborne and", "osborne and espenshade 2009", "espenshade 2009 weber", "2009 weber et", "weber et al. 2004", "et al. 2004 .
", "al. 2004 .
newly", "2004 .
newly synthesized", ".
newly synthesized srebps", "newly synthesized srebps are", "synthesized srebps are transmembrane", "srebps are transmembrane proteins", "are transmembrane proteins that", "transmembrane proteins that bind", "proteins that bind scap", "that bind scap in", "bind scap in the", "scap in the endoplasmic", "in the endoplasmic reticulum", "endoplasmic reticulum er", "er membrane. scap", "membrane. scap binds cholesterol", "scap binds cholesterol which", "binds cholesterol which causes", "cholesterol which causes a", "which causes a conformational", "causes a conformational change", "a conformational change that", "conformational change that allows", "change that allows scap", "that allows scap to", "allows scap to interact", "scap to interact with", "to interact with insig", "with insig retaining", "insig retaining the", "retaining the scap:srebp complex", "the scap:srebp complex in", "scap:srebp complex in the", "complex in the er.", "in the er. insig", "the er. insig binds", "er. insig binds oxysterols", "binds oxysterols which", "oxysterols which cause", "which cause insig to", "cause insig to bind", "insig to bind scap", "to bind scap and", "bind scap and retain", "scap and retain scap:srebp", "and retain scap:srebp in", "retain scap:srebp in the", "scap:srebp in the endoplasmic", "in the endoplasmic reticulum.
in", "the endoplasmic reticulum.
in low", "endoplasmic reticulum.
in low cholesterol", "low cholesterol below", "cholesterol below about", "below about 5 mol%", "5 mol% scap", "mol% scap no", "scap no longer interacts", "no longer interacts with", "longer interacts with cholesterol", "interacts with cholesterol or", "with cholesterol or insig", "cholesterol or insig and", "or insig and binds", "insig and binds sec24", "and binds sec24 of", "binds sec24 of the", "sec24 of the copii", "of the copii coat", "the copii coat complex", "copii coat complex instead.", "coat complex instead. thus", "complex instead. thus scap:srebp", "instead. thus scap:srebp transits", "thus scap:srebp transits with", "scap:srebp transits with the", "transits with the copii", "with the copii complex", "the copii complex from", "copii complex from the", "complex from the er", "from the er to", "the er to the", "er to the golgi.", "to the golgi. in", "the golgi. in the", "golgi. in the golgi", "in the golgi srebp", "the golgi srebp is", "golgi srebp is cleaved", "srebp is cleaved by", "is cleaved by s1p", "cleaved by s1p and", "by s1p and then", "s1p and then by", "and then by s2p", "by s2p releasing", "s2p releasing the", "releasing the n terminal", "the n terminal fragment", "n terminal fragment of", "terminal fragment of srebp", "fragment of srebp into", "of srebp into the", "srebp into the cytosol.", "into the cytosol. the", "the cytosol. the n", "cytosol. the n terminal", "n terminal fragment is", "terminal fragment is imported", "fragment is imported to", "is imported to the", "imported to the nucleus", "to the nucleus by", "the nucleus by importin", "nucleus by importin beta", "by importin beta and", "importin beta and then", "beta and then acts", "and then acts with", "then acts with other", "acts with other factors", "other factors such", "factors such as", "such as sp1 and", "as sp1 and nf", "sp1 and nf y", "nf y to", "y to activate", "to activate transcription of", "activate transcription of target", "transcription of target genes.", "of target genes. targets", "target genes. targets of", "genes. targets of srebp", "targets of srebp include", "of srebp include the", "srebp include the genes", "include the genes encoding", "the genes encoding all", "genes encoding all enzymes", "encoding all enzymes of", "all enzymes of cholesterol", "enzymes of cholesterol biosynthesis", "of cholesterol biosynthesis and", "cholesterol biosynthesis and several", "biosynthesis and several genes", "and several genes involved", "several genes involved in", "genes involved in lipogenesis.", "involved in lipogenesis. srebp2", "in lipogenesis. srebp2 most", "lipogenesis. srebp2 most strongly", "srebp2 most strongly activates", "most strongly activates cholesterol", "strongly activates cholesterol biosynthesis", "activates cholesterol biosynthesis while", "cholesterol biosynthesis while srebp1c", "biosynthesis while srebp1c most", "while srebp1c most strongly", "srebp1c most strongly activates", "most strongly activates lipogenesis.", "sterol regulatory element binding proteins", "element binding proteins srebps", "proteins srebps srebfs", "srebps srebfs respond", "srebfs respond to low", "respond to low cholesterol concentrations", "to low cholesterol concentrations by", "low cholesterol concentrations by transiting", "cholesterol concentrations by transiting to", "concentrations by transiting to the", "by transiting to the nucleus", "transiting to the nucleus and", "to the nucleus and activating", "the nucleus and activating genes", "nucleus and activating genes involved", "and activating genes involved in", "activating genes involved in cholesterol", "genes involved in cholesterol and", "involved in cholesterol and lipid", "in cholesterol and lipid biosynthesis", "and lipid biosynthesis reviewed", "lipid biosynthesis reviewed in", "biosynthesis reviewed in brown", "reviewed in brown and goldstein", "in brown and goldstein 2009", "and goldstein 2009 osborne", "goldstein 2009 osborne and", "2009 osborne and espenshade", "and espenshade 2009 weber", "espenshade 2009 weber et", "2009 weber et al.", "weber et al. 2004 .
", "et al. 2004 .
newly", "al. 2004 .
newly synthesized", "2004 .
newly synthesized srebps", ".
newly synthesized srebps are", "newly synthesized srebps are transmembrane", "synthesized srebps are transmembrane proteins", "srebps are transmembrane proteins that", "are transmembrane proteins that bind", "transmembrane proteins that bind scap", "proteins that bind scap in", "that bind scap in the", "bind scap in the endoplasmic", "scap in the endoplasmic reticulum", "the endoplasmic reticulum er", "reticulum er membrane.", "er membrane. scap binds", "membrane. scap binds cholesterol which", "scap binds cholesterol which causes", "binds cholesterol which causes a", "cholesterol which causes a conformational", "which causes a conformational change", "causes a conformational change that", "a conformational change that allows", "conformational change that allows scap", "change that allows scap to", "that allows scap to interact", "allows scap to interact with", "scap to interact with insig", "interact with insig retaining", "with insig retaining the", "insig retaining the scap:srebp", "retaining the scap:srebp complex in", "the scap:srebp complex in the", "scap:srebp complex in the er.", "complex in the er. insig", "in the er. insig binds", "the er. insig binds oxysterols", "insig binds oxysterols which", "binds oxysterols which cause", "oxysterols which cause insig", "which cause insig to bind", "cause insig to bind scap", "insig to bind scap and", "to bind scap and retain", "bind scap and retain scap:srebp", "scap and retain scap:srebp in", "and retain scap:srebp in the", "retain scap:srebp in the endoplasmic", "scap:srebp in the endoplasmic reticulum.
in", "in the endoplasmic reticulum.
in low", "the endoplasmic reticulum.
in low cholesterol", "reticulum.
in low cholesterol below", "low cholesterol below about", "cholesterol below about 5", "about 5 mol% scap", "5 mol% scap no", "mol% scap no longer", "scap no longer interacts with", "no longer interacts with cholesterol", "longer interacts with cholesterol or", "interacts with cholesterol or insig", "with cholesterol or insig and", "cholesterol or insig and binds", "or insig and binds sec24", "insig and binds sec24 of", "and binds sec24 of the", "binds sec24 of the copii", "sec24 of the copii coat", "of the copii coat complex", "the copii coat complex instead.", "copii coat complex instead. thus", "coat complex instead. thus scap:srebp", "complex instead. thus scap:srebp transits", "instead. thus scap:srebp transits with", "thus scap:srebp transits with the", "scap:srebp transits with the copii", "transits with the copii complex", "with the copii complex from", "the copii complex from the", "copii complex from the er", "complex from the er to", "from the er to the", "the er to the golgi.", "er to the golgi. in", "to the golgi. in the", "the golgi. in the golgi", "golgi. in the golgi srebp", "in the golgi srebp is", "the golgi srebp is cleaved", "golgi srebp is cleaved by", "srebp is cleaved by s1p", "is cleaved by s1p and", "cleaved by s1p and then", "by s1p and then by", "s1p and then by s2p", "then by s2p releasing", "by s2p releasing the", "s2p releasing the n", "releasing the n terminal fragment", "the n terminal fragment of", "n terminal fragment of srebp", "terminal fragment of srebp into", "fragment of srebp into the", "of srebp into the cytosol.", "srebp into the cytosol. the", "into the cytosol. the n", "the cytosol. the n terminal", "cytosol. the n terminal fragment", "the n terminal fragment is", "n terminal fragment is imported", "terminal fragment is imported to", "fragment is imported to the", "is imported to the nucleus", "imported to the nucleus by", "to the nucleus by importin", "the nucleus by importin beta", "nucleus by importin beta and", "by importin beta and then", "importin beta and then acts", "beta and then acts with", "and then acts with other", "then acts with other factors", "with other factors such", "other factors such as", "factors such as sp1", "such as sp1 and nf", "as sp1 and nf y", "and nf y to", "nf y to activate", "y to activate transcription", "to activate transcription of target", "activate transcription of target genes.", "transcription of target genes. targets", "of target genes. targets of", "target genes. targets of srebp", "genes. targets of srebp include", "targets of srebp include the", "of srebp include the genes", "srebp include the genes encoding", "include the genes encoding all", "the genes encoding all enzymes", "genes encoding all enzymes of", "encoding all enzymes of cholesterol", "all enzymes of cholesterol biosynthesis", "enzymes of cholesterol biosynthesis and", "of cholesterol biosynthesis and several", "cholesterol biosynthesis and several genes", "biosynthesis and several genes involved", "and several genes involved in", "several genes involved in lipogenesis.", "genes involved in lipogenesis. srebp2", "involved in lipogenesis. srebp2 most", "in lipogenesis. srebp2 most strongly", "lipogenesis. srebp2 most strongly activates", "srebp2 most strongly activates cholesterol", "most strongly activates cholesterol biosynthesis", "strongly activates cholesterol biosynthesis while", "activates cholesterol biosynthesis while srebp1c", "cholesterol biosynthesis while srebp1c most", "biosynthesis while srebp1c most strongly", "while srebp1c most strongly activates", "srebp1c most strongly activates lipogenesis." ] }, { "record_id": "GLY_000594_1_723", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "203927", "r hsa", "hsa 203927", "r hsa 203927" ] }, { "record_id": "GLY_000594_1_723", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "microrna mirna", "mirna biogenesis", "microrna mirna biogenesis", "biogenesis of", "of micrornas", "can be", "be summarized", "summarized in", "in five", "five steps", "reviewed in", "in ketting", "ketting 2011", "nowotny and", "and yang", "yang 2009", "kim et", "et al.", "al. 2009", "chua et", "hannon and", "and he", "he 2004", "2004 :
1.", ":
1. transcription.", "transcription. mirna", "mirna transcripts", "transcripts may", "may come", "come from", "from autonomously", "autonomously transcribed", "transcribed genes", "they may", "may be", "be contained", "contained in", "in cotranscripts", "cotranscripts with", "with other", "other genes", "or they", "be located", "located in", "in introns", "introns of", "of host", "host genes.", "genes. most", "most mirnas", "mirnas are", "are transcribed", "transcribed by", "by rna", "rna polymerase", "polymerase ii", "however a", "a few", "few mirnas", "mirnas originate", "originate as", "as rna", "polymerase iii", "iii cotranscripts", "with neighboring", "neighboring repetitive", "repetitive elements.", "elements. the", "the initial", "initial transcript", "termed a", "a primary", "primary microrna", "pri mirna", "contains an", "an imperfectly", "imperfectly double", "double stranded", "stranded region", "region within", "within a", "a hairpin", "hairpin loop.", "loop. longer", "longer sequences", "sequences extend", "extend from", "from the", "the 5'", "5' and", "and 3'", "3' ends", "ends of", "of the", "the hairpin", "hairpin and", "and may", "may also", "also contain", "contain double", "stranded regions.", "regions.
2.", "
2. cleavage", "cleavage by", "by drosha.", "drosha. the", "the pri", "mirna are", "are removed", "removed during", "during endoribonucleolytic", "endoribonucleolytic cleavage", "by the", "the drosha", "drosha nuclease", "nuclease in", "in a", "a complex", "complex with", "with the", "the rna", "rna binding", "binding protein", "protein dgcr8", "the microprocessor", "microprocessor complex", "complex .", ". the", "the cleavage", "cleavage product", "product is", "is a", "a short", "short hairpin", "hairpin of", "of about", "about 60", "60 to", "to 70", "70 nt", "nt called", "called the", "the pre", "pre microrna", "pre mirna", "mirna .", ".
3.", "
3. nuclear", "nuclear export", "export by", "by exportin", "exportin 5.", "5. the", "the resulting", "resulting pre", "mirna is", "is bound", "bound by", "exportin 5", "5 in", "with ran", "ran and", "and gtp.", "gtp. the", "the complex", "complex translocates", "translocates the", "mirna through", "through the", "the nuclear", "nuclear pore", "pore into", "into the", "the cytoplasm.", "cytoplasm.
4.", "
4. cleavage", "by dicer1.", "dicer1. once", "once in", "in the", "the cytoplasm", "cytoplasm the", "the risc", "risc loading", "loading complex", "complex which", "which contains", "contains dicer1", "an argonaute", "argonaute protein", "protein and", "and either", "either tarbp2", "tarbp2 or", "or prkra.", "prkra. dicer1", "dicer1 cleaves", "cleaves the", "mirna to", "to yield", "yield an", "stranded mirna", "mirna of", "about 21", "21 to", "to 23", "23 nucleotides.", "nucleotides. at", "at this", "this stage", "stage the", "the double", "mirna has", "has protruding", "protruding single", "single stranded", "stranded 3'", "of 2", "2 3", "3 nt.", "nt.
5.", "
5. incorporation", "incorporation into", "into rna", "rna induced", "induced silencing", "silencing complex", "and strand", "strand selection.", "selection. the", "is passed", "passed to", "to a", "a argonaute", "protein contained", "loading complex.", "complex. one", "one strand", "the passenger", "passenger strand", "will be", "be removed", "removed and", "and degraded", "the other", "other strand", "the guide", "guide strand", "be retained", "retained and", "and will", "will guide", "guide the", "the argonaute:mirna", "argonaute:mirna complex", "to target", "target mrnas.
the", "mrnas.
the human", "human genome", "genome encodes", "encodes 4", "4 argonaute", "argonaute proteins", "however only", "only ago2", "can cleave", "cleave target", "target mrnas", "mrnas with", "with perfect", "perfect or", "or nearly", "nearly perfect", "perfect complementarity", "complementarity to", "to the", "guide mirna.", "mirna. for", "for complexes", "complexes that", "that contain", "contain ago2", "cleavage of", "strand of", "mirna accompanies", "accompanies removal", "removal of", "passenger strand.", "strand. complexes", "complexes containing", "containing other", "other argonautes", "argonautes may", "may use", "use a", "a helicase", "helicase to", "to remove", "remove the", "strand but", "but this", "this is", "is not", "not fully", "fully known.", "known. the", "resulting mirna", "mirna loaded", "loaded ago2", "ago2 is", "is predominantly", "predominantly located", "in complexes", "complexes with", "with tarbp2", "or prkra", "prkra at", "at the", "the cytosolic", "cytosolic face", "face of", "the rough", "rough endoplasmic", "endoplasmic reticulum.", "reticulum. ago2", "and dicer1", "dicer1 are", "are also", "also observed", "observed in", "the nucleus.", "biogenesis of micrornas", "micrornas mirnas", "mirnas can", "can be summarized", "be summarized in", "summarized in five", "in five steps", "steps reviewed", "reviewed in ketting", "in ketting 2011", "2011 nowotny", "nowotny and yang", "and yang 2009", "2009 kim", "kim et al.", "et al. 2009", "2009 chua", "chua et al.", "2009 hannon", "hannon and he", "and he 2004", "he 2004 :
1.", "2004 :
1. transcription.", ":
1. transcription. mirna", "transcription. mirna transcripts", "mirna transcripts may", "transcripts may come", "may come from", "come from autonomously", "from autonomously transcribed", "autonomously transcribed genes", "genes they", "they may be", "may be contained", "be contained in", "contained in cotranscripts", "in cotranscripts with", "cotranscripts with other", "with other genes", "genes or", "or they may", "may be located", "be located in", "located in introns", "in introns of", "introns of host", "of host genes.", "host genes. most", "genes. most mirnas", "most mirnas are", "mirnas are transcribed", "are transcribed by", "transcribed by rna", "by rna polymerase", "rna polymerase ii", "ii however", "however a few", "a few mirnas", "few mirnas originate", "mirnas originate as", "originate as rna", "as rna polymerase", "rna polymerase iii", "polymerase iii cotranscripts", "iii cotranscripts with", "cotranscripts with neighboring", "with neighboring repetitive", "neighboring repetitive elements.", "repetitive elements. the", "elements. the initial", "the initial transcript", "transcript termed", "termed a primary", "a primary microrna", "microrna pri", "contains an imperfectly", "an imperfectly double", "imperfectly double stranded", "double stranded region", "stranded region within", "region within a", "within a hairpin", "a hairpin loop.", "hairpin loop. longer", "loop. longer sequences", "longer sequences extend", "sequences extend from", "extend from the", "from the 5'", "the 5' and", "5' and 3'", "and 3' ends", "3' ends of", "ends of the", "of the hairpin", "the hairpin and", "hairpin and may", "and may also", "may also contain", "also contain double", "contain double stranded", "double stranded regions.", "stranded regions.
2.", "regions.
2. cleavage", "
2. cleavage by", "cleavage by drosha.", "by drosha. the", "drosha. the 5'", "of the pri", "the pri mirna", "pri mirna are", "mirna are removed", "are removed during", "removed during endoribonucleolytic", "during endoribonucleolytic cleavage", "endoribonucleolytic cleavage by", "cleavage by the", "by the drosha", "the drosha nuclease", "drosha nuclease in", "nuclease in a", "in a complex", "a complex with", "complex with the", "with the rna", "the rna binding", "rna binding protein", "binding protein dgcr8", "dgcr8 the", "the microprocessor complex", "microprocessor complex .", "complex . the", ". the cleavage", "the cleavage product", "cleavage product is", "product is a", "is a short", "a short hairpin", "short hairpin of", "hairpin of about", "of about 60", "about 60 to", "60 to 70", "to 70 nt", "70 nt called", "nt called the", "called the pre", "the pre microrna", "microrna pre", "pre mirna .", "mirna .
3.", ".
3. nuclear", "
3. nuclear export", "nuclear export by", "export by exportin", "by exportin 5.", "exportin 5. the", "5. the resulting", "the resulting pre", "resulting pre mirna", "pre mirna is", "mirna is bound", "is bound by", "bound by exportin", "by exportin 5", "exportin 5 in", "5 in a", "complex with ran", "with ran and", "ran and gtp.", "and gtp. the", "gtp. the complex", "the complex translocates", "complex translocates the", "translocates the pre", "the pre mirna", "pre mirna through", "mirna through the", "through the nuclear", "the nuclear pore", "nuclear pore into", "pore into the", "into the cytoplasm.", "the cytoplasm.
4.", "cytoplasm.
4. cleavage", "
4. cleavage by", "cleavage by dicer1.", "by dicer1. once", "dicer1. once in", "once in the", "in the cytoplasm", "the cytoplasm the", "cytoplasm the pre", "bound by the", "by the risc", "the risc loading", "risc loading complex", "loading complex which", "complex which contains", "which contains dicer1", "dicer1 an", "an argonaute protein", "argonaute protein and", "protein and either", "and either tarbp2", "either tarbp2 or", "tarbp2 or prkra.", "or prkra. dicer1", "prkra. dicer1 cleaves", "dicer1 cleaves the", "cleaves the pre", "pre mirna to", "mirna to yield", "to yield an", "yield an imperfectly", "double stranded mirna", "stranded mirna of", "mirna of about", "of about 21", "about 21 to", "21 to 23", "to 23 nucleotides.", "23 nucleotides. at", "nucleotides. at this", "at this stage", "this stage the", "stage the double", "the double stranded", "stranded mirna has", "mirna has protruding", "has protruding single", "protruding single stranded", "single stranded 3'", "stranded 3' ends", "ends of 2", "of 2 3", "2 3 nt.", "3 nt.
5.", "nt.
5. incorporation", "
5. incorporation into", "incorporation into rna", "into rna induced", "rna induced silencing", "induced silencing complex", "complex risc", "risc and", "and strand selection.", "strand selection. the", "selection. the double", "stranded mirna is", "mirna is passed", "is passed to", "passed to a", "to a argonaute", "a argonaute protein", "argonaute protein contained", "protein contained in", "contained in the", "in the risc", "risc loading complex.", "loading complex. one", "complex. one strand", "strand the", "the passenger strand", "strand will", "will be removed", "be removed and", "removed and degraded", "degraded the", "the other strand", "the guide strand", "will be retained", "be retained and", "retained and will", "and will guide", "will guide the", "guide the argonaute:mirna", "the argonaute:mirna complex", "risc to", "to target mrnas.
the", "target mrnas.
the human", "mrnas.
the human genome", "human genome encodes", "genome encodes 4", "encodes 4 argonaute", "4 argonaute proteins", "proteins ago1", "ago1 eif2c1", "ago2 eif2c2", "ago3 eif2c3", "ago4 eif2c4", "however only ago2", "eif2c2 can", "can cleave target", "cleave target mrnas", "target mrnas with", "mrnas with perfect", "with perfect or", "perfect or nearly", "or nearly perfect", "nearly perfect complementarity", "perfect complementarity to", "complementarity to the", "to the guide", "the guide mirna.", "guide mirna. for", "mirna. for complexes", "for complexes that", "complexes that contain", "that contain ago2", "ago2 cleavage", "cleavage of the", "of the passenger", "passenger strand of", "strand of the", "of the double", "stranded mirna accompanies", "mirna accompanies removal", "accompanies removal of", "removal of the", "the passenger strand.", "passenger strand. complexes", "strand. complexes containing", "complexes containing other", "containing other argonautes", "other argonautes may", "argonautes may use", "may use a", "use a helicase", "a helicase to", "helicase to remove", "to remove the", "remove the passenger", "passenger strand but", "strand but this", "but this is", "this is not", "is not fully", "not fully known.", "fully known. the", "known. the resulting", "the resulting mirna", "resulting mirna loaded", "mirna loaded ago2", "loaded ago2 is", "ago2 is predominantly", "is predominantly located", "predominantly located in", "located in complexes", "in complexes with", "complexes with tarbp2", "with tarbp2 or", "tarbp2 or prkra", "or prkra at", "prkra at the", "at the cytosolic", "the cytosolic face", "cytosolic face of", "face of the", "of the rough", "the rough endoplasmic", "rough endoplasmic reticulum.", "endoplasmic reticulum. ago2", "ago2 tarbp2", "tarbp2 and", "and dicer1 are", "dicer1 are also", "are also observed", "also observed in", "observed in the", "in the nucleus.", "of micrornas mirnas", "mirnas can be", "can be summarized in", "be summarized in five", "summarized in five steps", "five steps reviewed", "steps reviewed in", "reviewed in ketting 2011", "ketting 2011 nowotny", "2011 nowotny and", "nowotny and yang 2009", "yang 2009 kim", "2009 kim et", "kim et al. 2009", "al. 2009 chua", "2009 chua et", "chua et al. 2009", "al. 2009 hannon", "2009 hannon and", "hannon and he 2004", "and he 2004 :
1.", "he 2004 :
1. transcription.", "2004 :
1. transcription. mirna", ":
1. transcription. mirna transcripts", "transcription. mirna transcripts may", "mirna transcripts may come", "transcripts may come from", "may come from autonomously", "come from autonomously transcribed", "from autonomously transcribed genes", "transcribed genes they", "genes they may", "they may be contained", "may be contained in", "be contained in cotranscripts", "contained in cotranscripts with", "in cotranscripts with other", "cotranscripts with other genes", "other genes or", "genes or they", "or they may be", "they may be located", "may be located in", "be located in introns", "located in introns of", "in introns of host", "introns of host genes.", "of host genes. most", "host genes. most mirnas", "genes. most mirnas are", "most mirnas are transcribed", "mirnas are transcribed by", "are transcribed by rna", "transcribed by rna polymerase", "by rna polymerase ii", "polymerase ii however", "ii however a", "however a few mirnas", "a few mirnas originate", "few mirnas originate as", "mirnas originate as rna", "originate as rna polymerase", "as rna polymerase iii", "rna polymerase iii cotranscripts", "polymerase iii cotranscripts with", "iii cotranscripts with neighboring", "cotranscripts with neighboring repetitive", "with neighboring repetitive elements.", "neighboring repetitive elements. the", "repetitive elements. the initial", "elements. the initial transcript", "initial transcript termed", "transcript termed a", "termed a primary microrna", "primary microrna pri", "microrna pri mirna", "mirna contains", "contains an imperfectly double", "an imperfectly double stranded", "imperfectly double stranded region", "double stranded region within", "stranded region within a", "region within a hairpin", "within a hairpin loop.", "a hairpin loop. longer", "hairpin loop. longer sequences", "loop. longer sequences extend", "longer sequences extend from", "sequences extend from the", "extend from the 5'", "from the 5' and", "the 5' and 3'", "5' and 3' ends", "and 3' ends of", "3' ends of the", "ends of the hairpin", "of the hairpin and", "the hairpin and may", "hairpin and may also", "and may also contain", "may also contain double", "also contain double stranded", "contain double stranded regions.", "double stranded regions.
2.", "stranded regions.
2. cleavage", "regions.
2. cleavage by", "
2. cleavage by drosha.", "cleavage by drosha. the", "by drosha. the 5'", "drosha. the 5' and", "ends of the pri", "of the pri mirna", "the pri mirna are", "pri mirna are removed", "mirna are removed during", "are removed during endoribonucleolytic", "removed during endoribonucleolytic cleavage", "during endoribonucleolytic cleavage by", "endoribonucleolytic cleavage by the", "cleavage by the drosha", "by the drosha nuclease", "the drosha nuclease in", "drosha nuclease in a", "nuclease in a complex", "in a complex with", "a complex with the", "complex with the rna", "with the rna binding", "the rna binding protein", "rna binding protein dgcr8", "protein dgcr8 the", "dgcr8 the microprocessor", "the microprocessor complex .", "microprocessor complex . the", "complex . the cleavage", ". the cleavage product", "the cleavage product is", "cleavage product is a", "product is a short", "is a short hairpin", "a short hairpin of", "short hairpin of about", "hairpin of about 60", "of about 60 to", "about 60 to 70", "60 to 70 nt", "to 70 nt called", "70 nt called the", "nt called the pre", "called the pre microrna", "pre microrna pre", "microrna pre mirna", "pre mirna .
3.", "mirna .
3. nuclear", ".
3. nuclear export", "
3. nuclear export by", "nuclear export by exportin", "export by exportin 5.", "by exportin 5. the", "exportin 5. the resulting", "5. the resulting pre", "the resulting pre mirna", "resulting pre mirna is", "pre mirna is bound", "mirna is bound by", "is bound by exportin", "bound by exportin 5", "by exportin 5 in", "exportin 5 in a", "5 in a complex", "a complex with ran", "complex with ran and", "with ran and gtp.", "ran and gtp. the", "and gtp. the complex", "gtp. the complex translocates", "the complex translocates the", "complex translocates the pre", "translocates the pre mirna", "the pre mirna through", "pre mirna through the", "mirna through the nuclear", "through the nuclear pore", "the nuclear pore into", "nuclear pore into the", "pore into the cytoplasm.", "into the cytoplasm.
4.", "the cytoplasm.
4. cleavage", "cytoplasm.
4. cleavage by", "
4. cleavage by dicer1.", "cleavage by dicer1. once", "by dicer1. once in", "dicer1. once in the", "once in the cytoplasm", "in the cytoplasm the", "the cytoplasm the pre", "cytoplasm the pre mirna", "the pre mirna is", "is bound by the", "bound by the risc", "by the risc loading", "the risc loading complex", "risc loading complex which", "loading complex which contains", "complex which contains dicer1", "contains dicer1 an", "dicer1 an argonaute", "an argonaute protein and", "argonaute protein and either", "protein and either tarbp2", "and either tarbp2 or", "either tarbp2 or prkra.", "tarbp2 or prkra. dicer1", "or prkra. dicer1 cleaves", "prkra. dicer1 cleaves the", "dicer1 cleaves the pre", "cleaves the pre mirna", "the pre mirna to", "pre mirna to yield", "mirna to yield an", "to yield an imperfectly", "yield an imperfectly double", "imperfectly double stranded mirna", "double stranded mirna of", "stranded mirna of about", "mirna of about 21", "of about 21 to", "about 21 to 23", "21 to 23 nucleotides.", "to 23 nucleotides. at", "23 nucleotides. at this", "nucleotides. at this stage", "at this stage the", "this stage the double", "stage the double stranded", "the double stranded mirna", "double stranded mirna has", "stranded mirna has protruding", "mirna has protruding single", "has protruding single stranded", "protruding single stranded 3'", "single stranded 3' ends", "stranded 3' ends of", "3' ends of 2", "ends of 2 3", "of 2 3 nt.", "2 3 nt.
5.", "3 nt.
5. incorporation", "nt.
5. incorporation into", "
5. incorporation into rna", "incorporation into rna induced", "into rna induced silencing", "rna induced silencing complex", "silencing complex risc", "risc and strand", "and strand selection. the", "strand selection. the double", "selection. the double stranded", "double stranded mirna is", "stranded mirna is passed", "mirna is passed to", "is passed to a", "passed to a argonaute", "to a argonaute protein", "a argonaute protein contained", "argonaute protein contained in", "protein contained in the", "contained in the risc", "in the risc loading", "the risc loading complex.", "risc loading complex. one", "loading complex. one strand", "one strand the", "strand the passenger", "passenger strand will", "strand will be", "will be removed and", "be removed and degraded", "and degraded the", "degraded the other", "other strand the", "strand the guide", "guide strand will", "will be retained and", "be retained and will", "retained and will guide", "and will guide the", "will guide the argonaute:mirna", "guide the argonaute:mirna complex", "argonaute:mirna complex risc", "risc to target", "to target mrnas.
the human", "target mrnas.
the human genome", "mrnas.
the human genome encodes", "human genome encodes 4", "genome encodes 4 argonaute", "encodes 4 argonaute proteins", "argonaute proteins ago1", "eif2c1 ago2", "eif2c2 ago3", "eif2c3 ago4", "only ago2 eif2c2", "eif2c2 can cleave", "can cleave target mrnas", "cleave target mrnas with", "target mrnas with perfect", "mrnas with perfect or", "with perfect or nearly", "perfect or nearly perfect", "or nearly perfect complementarity", "nearly perfect complementarity to", "perfect complementarity to the", "complementarity to the guide", "to the guide mirna.", "the guide mirna. for", "guide mirna. for complexes", "mirna. for complexes that", "for complexes that contain", "complexes that contain ago2", "contain ago2 cleavage", "ago2 cleavage of", "cleavage of the passenger", "of the passenger strand", "the passenger strand of", "passenger strand of the", "strand of the double", "of the double stranded", "double stranded mirna accompanies", "stranded mirna accompanies removal", "mirna accompanies removal of", "accompanies removal of the", "removal of the passenger", "of the passenger strand.", "the passenger strand. complexes", "passenger strand. complexes containing", "strand. complexes containing other", "complexes containing other argonautes", "containing other argonautes may", "other argonautes may use", "argonautes may use a", "may use a helicase", "use a helicase to", "a helicase to remove", "helicase to remove the", "to remove the passenger", "remove the passenger strand", "the passenger strand but", "passenger strand but this", "strand but this is", "but this is not", "this is not fully", "is not fully known.", "not fully known. the", "fully known. the resulting", "known. the resulting mirna", "the resulting mirna loaded", "resulting mirna loaded ago2", "mirna loaded ago2 is", "loaded ago2 is predominantly", "ago2 is predominantly located", "is predominantly located in", "predominantly located in complexes", "located in complexes with", "in complexes with tarbp2", "complexes with tarbp2 or", "with tarbp2 or prkra", "tarbp2 or prkra at", "or prkra at the", "prkra at the cytosolic", "at the cytosolic face", "the cytosolic face of", "cytosolic face of the", "face of the rough", "of the rough endoplasmic", "the rough endoplasmic reticulum.", "rough endoplasmic reticulum. ago2", "reticulum. ago2 tarbp2", "tarbp2 and dicer1", "and dicer1 are also", "dicer1 are also observed", "are also observed in", "also observed in the", "observed in the nucleus.", "biogenesis of micrornas mirnas", "micrornas mirnas can", "mirnas can be summarized", "can be summarized in five", "be summarized in five steps", "in five steps reviewed", "five steps reviewed in", "steps reviewed in ketting", "in ketting 2011 nowotny", "ketting 2011 nowotny and", "2011 nowotny and yang", "and yang 2009 kim", "yang 2009 kim et", "2009 kim et al.", "et al. 2009 chua", "al. 2009 chua et", "2009 chua et al.", "et al. 2009 hannon", "al. 2009 hannon and", "2009 hannon and he", "hannon and he 2004 :
1.", "and he 2004 :
1. transcription.", "he 2004 :
1. transcription. mirna", "2004 :
1. transcription. mirna transcripts", ":
1. transcription. mirna transcripts may", "transcription. mirna transcripts may come", "mirna transcripts may come from", "transcripts may come from autonomously", "may come from autonomously transcribed", "come from autonomously transcribed genes", "autonomously transcribed genes they", "transcribed genes they may", "genes they may be", "they may be contained in", "may be contained in cotranscripts", "be contained in cotranscripts with", "contained in cotranscripts with other", "in cotranscripts with other genes", "with other genes or", "other genes or they", "genes or they may", "or they may be located", "they may be located in", "may be located in introns", "be located in introns of", "located in introns of host", "in introns of host genes.", "introns of host genes. most", "of host genes. most mirnas", "host genes. most mirnas are", "genes. most mirnas are transcribed", "most mirnas are transcribed by", "mirnas are transcribed by rna", "are transcribed by rna polymerase", "transcribed by rna polymerase ii", "rna polymerase ii however", "polymerase ii however a", "ii however a few", "however a few mirnas originate", "a few mirnas originate as", "few mirnas originate as rna", "mirnas originate as rna polymerase", "originate as rna polymerase iii", "as rna polymerase iii cotranscripts", "rna polymerase iii cotranscripts with", "polymerase iii cotranscripts with neighboring", "iii cotranscripts with neighboring repetitive", "cotranscripts with neighboring repetitive elements.", "with neighboring repetitive elements. the", "neighboring repetitive elements. the initial", "repetitive elements. the initial transcript", "the initial transcript termed", "initial transcript termed a", "transcript termed a primary", "a primary microrna pri", "primary microrna pri mirna", "pri mirna contains", "mirna contains an", "contains an imperfectly double stranded", "an imperfectly double stranded region", "imperfectly double stranded region within", "double stranded region within a", "stranded region within a hairpin", "region within a hairpin loop.", "within a hairpin loop. longer", "a hairpin loop. longer sequences", "hairpin loop. longer sequences extend", "loop. longer sequences extend from", "longer sequences extend from the", "sequences extend from the 5'", "extend from the 5' and", "from the 5' and 3'", "the 5' and 3' ends", "5' and 3' ends of", "and 3' ends of the", "3' ends of the hairpin", "ends of the hairpin and", "of the hairpin and may", "the hairpin and may also", "hairpin and may also contain", "and may also contain double", "may also contain double stranded", "also contain double stranded regions.", "contain double stranded regions.
2.", "double stranded regions.
2. cleavage", "stranded regions.
2. cleavage by", "regions.
2. cleavage by drosha.", "
2. cleavage by drosha. the", "cleavage by drosha. the 5'", "by drosha. the 5' and", "drosha. the 5' and 3'", "3' ends of the pri", "ends of the pri mirna", "of the pri mirna are", "the pri mirna are removed", "pri mirna are removed during", "mirna are removed during endoribonucleolytic", "are removed during endoribonucleolytic cleavage", "removed during endoribonucleolytic cleavage by", "during endoribonucleolytic cleavage by the", "endoribonucleolytic cleavage by the drosha", "cleavage by the drosha nuclease", "by the drosha nuclease in", "the drosha nuclease in a", "drosha nuclease in a complex", "nuclease in a complex with", "in a complex with the", "a complex with the rna", "complex with the rna binding", "with the rna binding protein", "the rna binding protein dgcr8", "binding protein dgcr8 the", "protein dgcr8 the microprocessor", "dgcr8 the microprocessor complex", "the microprocessor complex . the", "microprocessor complex . the cleavage", "complex . the cleavage product", ". the cleavage product is", "the cleavage product is a", "cleavage product is a short", "product is a short hairpin", "is a short hairpin of", "a short hairpin of about", "short hairpin of about 60", "hairpin of about 60 to", "of about 60 to 70", "about 60 to 70 nt", "60 to 70 nt called", "to 70 nt called the", "70 nt called the pre", "nt called the pre microrna", "the pre microrna pre", "pre microrna pre mirna", "microrna pre mirna .", "pre mirna .
3. nuclear", "mirna .
3. nuclear export", ".
3. nuclear export by", "
3. nuclear export by exportin", "nuclear export by exportin 5.", "export by exportin 5. the", "by exportin 5. the resulting", "exportin 5. the resulting pre", "5. the resulting pre mirna", "the resulting pre mirna is", "resulting pre mirna is bound", "pre mirna is bound by", "mirna is bound by exportin", "is bound by exportin 5", "bound by exportin 5 in", "by exportin 5 in a", "exportin 5 in a complex", "5 in a complex with", "in a complex with ran", "a complex with ran and", "complex with ran and gtp.", "with ran and gtp. the", "ran and gtp. the complex", "and gtp. the complex translocates", "gtp. the complex translocates the", "the complex translocates the pre", "complex translocates the pre mirna", "translocates the pre mirna through", "the pre mirna through the", "pre mirna through the nuclear", "mirna through the nuclear pore", "through the nuclear pore into", "the nuclear pore into the", "nuclear pore into the cytoplasm.", "pore into the cytoplasm.
4.", "into the cytoplasm.
4. cleavage", "the cytoplasm.
4. cleavage by", "cytoplasm.
4. cleavage by dicer1.", "
4. cleavage by dicer1. once", "cleavage by dicer1. once in", "by dicer1. once in the", "dicer1. once in the cytoplasm", "once in the cytoplasm the", "in the cytoplasm the pre", "the cytoplasm the pre mirna", "cytoplasm the pre mirna is", "the pre mirna is bound", "mirna is bound by the", "is bound by the risc", "bound by the risc loading", "by the risc loading complex", "the risc loading complex which", "risc loading complex which contains", "loading complex which contains dicer1", "which contains dicer1 an", "contains dicer1 an argonaute", "dicer1 an argonaute protein", "an argonaute protein and either", "argonaute protein and either tarbp2", "protein and either tarbp2 or", "and either tarbp2 or prkra.", "either tarbp2 or prkra. dicer1", "tarbp2 or prkra. dicer1 cleaves", "or prkra. dicer1 cleaves the", "prkra. dicer1 cleaves the pre", "dicer1 cleaves the pre mirna", "cleaves the pre mirna to", "the pre mirna to yield", "pre mirna to yield an", "mirna to yield an imperfectly", "to yield an imperfectly double", "yield an imperfectly double stranded", "an imperfectly double stranded mirna", "imperfectly double stranded mirna of", "double stranded mirna of about", "stranded mirna of about 21", "mirna of about 21 to", "of about 21 to 23", "about 21 to 23 nucleotides.", "21 to 23 nucleotides. at", "to 23 nucleotides. at this", "23 nucleotides. at this stage", "nucleotides. at this stage the", "at this stage the double", "this stage the double stranded", "stage the double stranded mirna", "the double stranded mirna has", "double stranded mirna has protruding", "stranded mirna has protruding single", "mirna has protruding single stranded", "has protruding single stranded 3'", "protruding single stranded 3' ends", "single stranded 3' ends of", "stranded 3' ends of 2", "3' ends of 2 3", "ends of 2 3 nt.", "of 2 3 nt.
5.", "2 3 nt.
5. incorporation", "3 nt.
5. incorporation into", "nt.
5. incorporation into rna", "
5. incorporation into rna induced", "incorporation into rna induced silencing", "into rna induced silencing complex", "induced silencing complex risc", "complex risc and", "risc and strand selection.", "and strand selection. the double", "strand selection. the double stranded", "selection. the double stranded mirna", "the double stranded mirna is", "double stranded mirna is passed", "stranded mirna is passed to", "mirna is passed to a", "is passed to a argonaute", "passed to a argonaute protein", "to a argonaute protein contained", "a argonaute protein contained in", "argonaute protein contained in the", "protein contained in the risc", "contained in the risc loading", "in the risc loading complex.", "the risc loading complex. one", "risc loading complex. one strand", "complex. one strand the", "one strand the passenger", "strand the passenger strand", "the passenger strand will", "passenger strand will be", "strand will be removed", "will be removed and degraded", "removed and degraded the", "and degraded the other", "degraded the other strand", "the other strand the", "other strand the guide", "strand the guide strand", "the guide strand will", "guide strand will be", "strand will be retained", "will be retained and will", "be retained and will guide", "retained and will guide the", "and will guide the argonaute:mirna", "will guide the argonaute:mirna complex", "the argonaute:mirna complex risc", "complex risc to", "risc to target mrnas.
the", "to target mrnas.
the human genome", "target mrnas.
the human genome encodes", "mrnas.
the human genome encodes 4", "human genome encodes 4 argonaute", "genome encodes 4 argonaute proteins", "4 argonaute proteins ago1", "proteins ago1 eif2c1", "eif2c4 however", "however only ago2 eif2c2", "ago2 eif2c2 can", "eif2c2 can cleave target", "can cleave target mrnas with", "cleave target mrnas with perfect", "target mrnas with perfect or", "mrnas with perfect or nearly", "with perfect or nearly perfect", "perfect or nearly perfect complementarity", "or nearly perfect complementarity to", "nearly perfect complementarity to the", "perfect complementarity to the guide", "complementarity to the guide mirna.", "to the guide mirna. for", "the guide mirna. for complexes", "guide mirna. for complexes that", "mirna. for complexes that contain", "for complexes that contain ago2", "that contain ago2 cleavage", "contain ago2 cleavage of", "ago2 cleavage of the", "cleavage of the passenger strand", "of the passenger strand of", "the passenger strand of the", "passenger strand of the double", "strand of the double stranded", "of the double stranded mirna", "the double stranded mirna accompanies", "double stranded mirna accompanies removal", "stranded mirna accompanies removal of", "mirna accompanies removal of the", "accompanies removal of the passenger", "removal of the passenger strand.", "of the passenger strand. complexes", "the passenger strand. complexes containing", "passenger strand. complexes containing other", "strand. complexes containing other argonautes", "complexes containing other argonautes may", "containing other argonautes may use", "other argonautes may use a", "argonautes may use a helicase", "may use a helicase to", "use a helicase to remove", "a helicase to remove the", "helicase to remove the passenger", "to remove the passenger strand", "remove the passenger strand but", "the passenger strand but this", "passenger strand but this is", "strand but this is not", "but this is not fully", "this is not fully known.", "is not fully known. the", "not fully known. the resulting", "fully known. the resulting mirna", "known. the resulting mirna loaded", "the resulting mirna loaded ago2", "resulting mirna loaded ago2 is", "mirna loaded ago2 is predominantly", "loaded ago2 is predominantly located", "ago2 is predominantly located in", "is predominantly located in complexes", "predominantly located in complexes with", "located in complexes with tarbp2", "in complexes with tarbp2 or", "complexes with tarbp2 or prkra", "with tarbp2 or prkra at", "tarbp2 or prkra at the", "or prkra at the cytosolic", "prkra at the cytosolic face", "at the cytosolic face of", "the cytosolic face of the", "cytosolic face of the rough", "face of the rough endoplasmic", "of the rough endoplasmic reticulum.", "the rough endoplasmic reticulum. ago2", "endoplasmic reticulum. ago2 tarbp2", "ago2 tarbp2 and", "tarbp2 and dicer1 are", "and dicer1 are also observed", "dicer1 are also observed in", "are also observed in the", "also observed in the nucleus." ] }, { "record_id": "GLY_000594_1_724", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5601884", "r hsa", "hsa 5601884", "r hsa 5601884" ] }, { "record_id": "GLY_000594_1_724", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "piwi interacting", "interacting rna", "piwi interacting rna", "rna pirna", "pirna biogenesis", "interacting rna pirna", "piwi interacting rna pirna", "rna pirna biogenesis", "in germ", "germ cells", "cells of", "of humans", "humans and", "and mice", "precursors of", "of piwi", "interacting rnas", "are transcribed", "transcribed from", "from a", "a few", "few hundred", "hundred sequence", "sequence clusters", "as well", "well as", "as individual", "individual transposons", "intergenic regions", "and genes", "genes in", "in the", "the genome.", "genome. these", "these longer", "longer transcripts", "transcripts are", "are processed", "processed to", "to yield", "yield pirnas", "pirnas of", "of 26", "26 30", "30 nucleotides", "nucleotides independently", "independently of", "of dicer", "the enzyme", "enzyme responsible", "responsible for", "for micrornas", "and small", "small interfering", "interfering rnas", "reviewed in", "in girard", "girard and", "and hannon", "hannon 2008", "siomi et", "et al.", "al. 2011", "ishizu et", "al. 2012", "pillai and", "and chuma", "chuma 2012", "bortvin 2013", "chuma and", "and nakano", "nakano 2013", "sato and", "and siomi", "siomi 2013", "2013 .", ". the", "the initial", "initial step", "step in", "in processing", "processing long", "long transcripts", "transcripts to", "to pirnas", "pirnas is", "is cleavage", "cleavage by", "by pld6", "which generates", "generates the", "the mature", "mature 5'", "5' end.", "end. the", "the cleavage", "cleavage products", "products of", "of pld6", "pld6 are", "are bound", "bound by", "by either", "either piwil1", "or piwil2", "in complexes", "complexes with", "with several", "several other", "other proteins.", "proteins. the", "the 3'", "3' end", "end is", "is trimmed", "trimmed by", "by an", "an unknown", "unknown exonuclease", "exonuclease to", "to generate", "generate the", "mature pirna.", "pirna. piwil1:pirna", "piwil1:pirna complexes", "complexes appear", "appear to", "to be", "be involved", "involved in", "in post", "post transcriptional", "transcriptional silencing", "silencing in", "the cytosol", "cytosol while", "while piwil2:pirna", "piwil2:pirna complexes", "complexes generate", "generate further", "further pirnas", "pirnas from", "from transposon", "transposon transcripts", "transcripts and", "and other", "other transcripts", "transcripts in", "the cytosol.", "cytosol. cleavage", "products from", "from piwil2:pirna", "piwil2:pirna may", "may be", "be loaded", "loaded into", "into either", "either piwil2", "piwil2 or", "or piwil4", "miwi2 .", ". loading", "loading into", "into piwil2", "piwil2 forms", "forms a", "a step", "in a", "a cytosolic", "cytosolic amplification", "amplification loop", "loop called", "called the", "the \\ping", "\\ping pong", "pong cycle\\", "cycle\\ which", "which yields", "yields further", "further piwil2:pirna", "complexes from", "from cleaved", "cleaved precursor", "precursor rnas.", "rnas. loading", "into piwil4", "piwil4 yields", "yields a", "a complex", "complex also", "also containing", "containing tdrd9", "tdrd9 that", "that translocates", "translocates to", "to the", "the nucleus", "nucleus and", "and directs", "directs dna", "dna methylation", "methylation of", "of cognate", "cognate loci", "causing transcriptional", "silencing during", "during spermatogenesis.", "spermatogenesis. transcriptional", "silencing by", "by pirnas", "is necessary", "necessary to", "to limit", "limit transposition", "transposition of", "of endogenous", "endogenous transposons", "transposons such", "such as", "as l1", "l1 elements", "elements in", "in germ cells", "germ cells of", "cells of humans", "of humans and", "humans and mice", "mice precursors", "precursors of piwi", "of piwi interacting", "piwi interacting rnas", "rnas pirnas", "pirnas are", "are transcribed from", "transcribed from a", "from a few", "a few hundred", "few hundred sequence", "hundred sequence clusters", "clusters as", "as well as", "well as individual", "as individual transposons", "transposons intergenic", "regions and", "and genes in", "genes in the", "in the genome.", "the genome. these", "genome. these longer", "these longer transcripts", "longer transcripts are", "transcripts are processed", "are processed to", "processed to yield", "to yield pirnas", "yield pirnas of", "pirnas of 26", "of 26 30", "26 30 nucleotides", "30 nucleotides independently", "nucleotides independently of", "independently of dicer", "dicer the", "the enzyme responsible", "enzyme responsible for", "responsible for micrornas", "micrornas mirnas", "mirnas and", "and small interfering", "small interfering rnas", "rnas sirnas", "reviewed in girard", "in girard and", "girard and hannon", "and hannon 2008", "2008 siomi", "siomi et al.", "et al. 2011", "2011 ishizu", "ishizu et al.", "et al. 2012", "2012 pillai", "pillai and chuma", "and chuma 2012", "2012 bortvin", "2013 chuma", "chuma and nakano", "and nakano 2013", "2013 sato", "sato and siomi", "and siomi 2013", "siomi 2013 .", "2013 . the", ". the initial", "the initial step", "initial step in", "step in processing", "in processing long", "processing long transcripts", "long transcripts to", "transcripts to pirnas", "to pirnas is", "pirnas is cleavage", "is cleavage by", "cleavage by pld6", "pld6 mitopld", "which generates the", "generates the mature", "the mature 5'", "mature 5' end.", "5' end. the", "end. the cleavage", "the cleavage products", "cleavage products of", "products of pld6", "of pld6 are", "pld6 are bound", "are bound by", "bound by either", "by either piwil1", "piwil1 hiwi", "hiwi miwi", "miwi or", "piwil2 hili", "hili mili", "mili in", "in complexes with", "complexes with several", "with several other", "several other proteins.", "other proteins. the", "proteins. the 3'", "the 3' end", "3' end is", "end is trimmed", "is trimmed by", "trimmed by an", "by an unknown", "an unknown exonuclease", "unknown exonuclease to", "exonuclease to generate", "to generate the", "generate the mature", "the mature pirna.", "mature pirna. piwil1:pirna", "pirna. piwil1:pirna complexes", "piwil1:pirna complexes appear", "complexes appear to", "appear to be", "to be involved", "be involved in", "involved in post", "in post transcriptional", "post transcriptional silencing", "transcriptional silencing in", "silencing in the", "in the cytosol", "the cytosol while", "cytosol while piwil2:pirna", "while piwil2:pirna complexes", "piwil2:pirna complexes generate", "complexes generate further", "generate further pirnas", "further pirnas from", "pirnas from transposon", "from transposon transcripts", "transposon transcripts and", "transcripts and other", "and other transcripts", "other transcripts in", "transcripts in the", "in the cytosol.", "the cytosol. cleavage", "cytosol. cleavage products", "cleavage products from", "products from piwil2:pirna", "from piwil2:pirna may", "piwil2:pirna may be", "may be loaded", "be loaded into", "loaded into either", "into either piwil2", "either piwil2 or", "piwil2 or piwil4", "piwil4 hiwi2", "hiwi2 miwi2", "miwi2 . loading", ". loading into", "loading into piwil2", "into piwil2 forms", "piwil2 forms a", "forms a step", "a step in", "step in a", "in a cytosolic", "a cytosolic amplification", "cytosolic amplification loop", "amplification loop called", "loop called the", "called the \\ping", "the \\ping pong", "\\ping pong cycle\\", "pong cycle\\ which", "cycle\\ which yields", "which yields further", "yields further piwil2:pirna", "further piwil2:pirna complexes", "piwil2:pirna complexes from", "complexes from cleaved", "from cleaved precursor", "cleaved precursor rnas.", "precursor rnas. loading", "rnas. loading into", "loading into piwil4", "into piwil4 yields", "piwil4 yields a", "yields a complex", "a complex also", "complex also containing", "also containing tdrd9", "containing tdrd9 that", "tdrd9 that translocates", "that translocates to", "translocates to the", "to the nucleus", "the nucleus and", "nucleus and directs", "and directs dna", "directs dna methylation", "dna methylation of", "methylation of cognate", "of cognate loci", "loci causing", "causing transcriptional silencing", "transcriptional silencing during", "silencing during spermatogenesis.", "during spermatogenesis. transcriptional", "spermatogenesis. transcriptional silencing", "transcriptional silencing by", "silencing by pirnas", "by pirnas is", "pirnas is necessary", "is necessary to", "necessary to limit", "to limit transposition", "limit transposition of", "transposition of endogenous", "of endogenous transposons", "endogenous transposons such", "transposons such as", "such as l1", "as l1 elements", "l1 elements in", "elements in the", "in germ cells of", "germ cells of humans", "cells of humans and", "of humans and mice", "and mice precursors", "mice precursors of", "precursors of piwi interacting", "of piwi interacting rnas", "interacting rnas pirnas", "pirnas are transcribed", "are transcribed from a", "transcribed from a few", "from a few hundred", "a few hundred sequence", "few hundred sequence clusters", "sequence clusters as", "clusters as well", "as well as individual", "well as individual transposons", "individual transposons intergenic", "transposons intergenic regions", "intergenic regions and", "regions and genes", "and genes in the", "genes in the genome.", "in the genome. these", "the genome. these longer", "genome. these longer transcripts", "these longer transcripts are", "longer transcripts are processed", "transcripts are processed to", "are processed to yield", "processed to yield pirnas", "to yield pirnas of", "yield pirnas of 26", "pirnas of 26 30", "of 26 30 nucleotides", "26 30 nucleotides independently", "30 nucleotides independently of", "nucleotides independently of dicer", "of dicer the", "dicer the enzyme", "the enzyme responsible for", "enzyme responsible for micrornas", "for micrornas mirnas", "mirnas and small", "and small interfering rnas", "interfering rnas sirnas", "sirnas reviewed", "reviewed in girard and", "in girard and hannon", "girard and hannon 2008", "hannon 2008 siomi", "2008 siomi et", "siomi et al. 2011", "al. 2011 ishizu", "2011 ishizu et", "ishizu et al. 2012", "al. 2012 pillai", "2012 pillai and", "pillai and chuma 2012", "chuma 2012 bortvin", "2012 bortvin 2013", "bortvin 2013 chuma", "2013 chuma and", "chuma and nakano 2013", "nakano 2013 sato", "2013 sato and", "sato and siomi 2013", "and siomi 2013 .", "siomi 2013 . the", "2013 . the initial", ". the initial step", "the initial step in", "initial step in processing", "step in processing long", "in processing long transcripts", "processing long transcripts to", "long transcripts to pirnas", "transcripts to pirnas is", "to pirnas is cleavage", "pirnas is cleavage by", "is cleavage by pld6", "by pld6 mitopld", "mitopld which", "which generates the mature", "generates the mature 5'", "the mature 5' end.", "mature 5' end. the", "5' end. the cleavage", "end. the cleavage products", "the cleavage products of", "cleavage products of pld6", "products of pld6 are", "of pld6 are bound", "pld6 are bound by", "are bound by either", "bound by either piwil1", "either piwil1 hiwi", "miwi or piwil2", "or piwil2 hili", "mili in complexes", "in complexes with several", "complexes with several other", "with several other proteins.", "several other proteins. the", "other proteins. the 3'", "proteins. the 3' end", "the 3' end is", "3' end is trimmed", "end is trimmed by", "is trimmed by an", "trimmed by an unknown", "by an unknown exonuclease", "an unknown exonuclease to", "unknown exonuclease to generate", "exonuclease to generate the", "to generate the mature", "generate the mature pirna.", "the mature pirna. piwil1:pirna", "mature pirna. piwil1:pirna complexes", "pirna. piwil1:pirna complexes appear", "piwil1:pirna complexes appear to", "complexes appear to be", "appear to be involved", "to be involved in", "be involved in post", "involved in post transcriptional", "in post transcriptional silencing", "post transcriptional silencing in", "transcriptional silencing in the", "silencing in the cytosol", "in the cytosol while", "the cytosol while piwil2:pirna", "cytosol while piwil2:pirna complexes", "while piwil2:pirna complexes generate", "piwil2:pirna complexes generate further", "complexes generate further pirnas", "generate further pirnas from", "further pirnas from transposon", "pirnas from transposon transcripts", "from transposon transcripts and", "transposon transcripts and other", "transcripts and other transcripts", "and other transcripts in", "other transcripts in the", "transcripts in the cytosol.", "in the cytosol. cleavage", "the cytosol. cleavage products", "cytosol. cleavage products from", "cleavage products from piwil2:pirna", "products from piwil2:pirna may", "from piwil2:pirna may be", "piwil2:pirna may be loaded", "may be loaded into", "be loaded into either", "loaded into either piwil2", "into either piwil2 or", "either piwil2 or piwil4", "or piwil4 hiwi2", "hiwi2 miwi2 .", "miwi2 . loading into", ". loading into piwil2", "loading into piwil2 forms", "into piwil2 forms a", "piwil2 forms a step", "forms a step in", "a step in a", "step in a cytosolic", "in a cytosolic amplification", "a cytosolic amplification loop", "cytosolic amplification loop called", "amplification loop called the", "loop called the \\ping", "called the \\ping pong", "the \\ping pong cycle\\", "\\ping pong cycle\\ which", "pong cycle\\ which yields", "cycle\\ which yields further", "which yields further piwil2:pirna", "yields further piwil2:pirna complexes", "further piwil2:pirna complexes from", "piwil2:pirna complexes from cleaved", "complexes from cleaved precursor", "from cleaved precursor rnas.", "cleaved precursor rnas. loading", "precursor rnas. loading into", "rnas. loading into piwil4", "loading into piwil4 yields", "into piwil4 yields a", "piwil4 yields a complex", "yields a complex also", "a complex also containing", "complex also containing tdrd9", "also containing tdrd9 that", "containing tdrd9 that translocates", "tdrd9 that translocates to", "that translocates to the", "translocates to the nucleus", "to the nucleus and", "the nucleus and directs", "nucleus and directs dna", "and directs dna methylation", "directs dna methylation of", "dna methylation of cognate", "methylation of cognate loci", "cognate loci causing", "loci causing transcriptional", "causing transcriptional silencing during", "transcriptional silencing during spermatogenesis.", "silencing during spermatogenesis. transcriptional", "during spermatogenesis. transcriptional silencing", "spermatogenesis. transcriptional silencing by", "transcriptional silencing by pirnas", "silencing by pirnas is", "by pirnas is necessary", "pirnas is necessary to", "is necessary to limit", "necessary to limit transposition", "to limit transposition of", "limit transposition of endogenous", "transposition of endogenous transposons", "of endogenous transposons such", "endogenous transposons such as", "transposons such as l1", "such as l1 elements", "as l1 elements in", "l1 elements in the", "elements in the genome.", "in germ cells of humans", "germ cells of humans and", "cells of humans and mice", "humans and mice precursors", "and mice precursors of", "mice precursors of piwi", "precursors of piwi interacting rnas", "piwi interacting rnas pirnas", "rnas pirnas are", "pirnas are transcribed from", "are transcribed from a few", "transcribed from a few hundred", "from a few hundred sequence", "a few hundred sequence clusters", "hundred sequence clusters as", "sequence clusters as well", "clusters as well as", "as well as individual transposons", "as individual transposons intergenic", "individual transposons intergenic regions", "intergenic regions and genes", "regions and genes in", "and genes in the genome.", "genes in the genome. these", "in the genome. these longer", "the genome. these longer transcripts", "genome. these longer transcripts are", "these longer transcripts are processed", "longer transcripts are processed to", "transcripts are processed to yield", "are processed to yield pirnas", "processed to yield pirnas of", "to yield pirnas of 26", "yield pirnas of 26 30", "pirnas of 26 30 nucleotides", "of 26 30 nucleotides independently", "26 30 nucleotides independently of", "30 nucleotides independently of dicer", "independently of dicer the", "of dicer the enzyme", "dicer the enzyme responsible", "the enzyme responsible for micrornas", "responsible for micrornas mirnas", "micrornas mirnas and", "mirnas and small interfering", "small interfering rnas sirnas", "sirnas reviewed in", "reviewed in girard and hannon", "in girard and hannon 2008", "and hannon 2008 siomi", "hannon 2008 siomi et", "2008 siomi et al.", "et al. 2011 ishizu", "al. 2011 ishizu et", "2011 ishizu et al.", "et al. 2012 pillai", "al. 2012 pillai and", "2012 pillai and chuma", "and chuma 2012 bortvin", "chuma 2012 bortvin 2013", "bortvin 2013 chuma and", "2013 chuma and nakano", "and nakano 2013 sato", "nakano 2013 sato and", "2013 sato and siomi", "sato and siomi 2013 .", "and siomi 2013 . the", "siomi 2013 . the initial", "2013 . the initial step", ". the initial step in", "the initial step in processing", "initial step in processing long", "step in processing long transcripts", "in processing long transcripts to", "processing long transcripts to pirnas", "long transcripts to pirnas is", "transcripts to pirnas is cleavage", "to pirnas is cleavage by", "pirnas is cleavage by pld6", "cleavage by pld6 mitopld", "mitopld which generates", "which generates the mature 5'", "generates the mature 5' end.", "the mature 5' end. the", "mature 5' end. the cleavage", "5' end. the cleavage products", "end. the cleavage products of", "the cleavage products of pld6", "cleavage products of pld6 are", "products of pld6 are bound", "of pld6 are bound by", "pld6 are bound by either", "are bound by either piwil1", "by either piwil1 hiwi", "piwil1 hiwi miwi", "hiwi miwi or", "piwil2 hili mili", "hili mili in", "mili in complexes with", "in complexes with several other", "complexes with several other proteins.", "with several other proteins. the", "several other proteins. the 3'", "other proteins. the 3' end", "proteins. the 3' end is", "the 3' end is trimmed", "3' end is trimmed by", "end is trimmed by an", "is trimmed by an unknown", "trimmed by an unknown exonuclease", "by an unknown exonuclease to", "an unknown exonuclease to generate", "unknown exonuclease to generate the", "exonuclease to generate the mature", "to generate the mature pirna.", "generate the mature pirna. piwil1:pirna", "the mature pirna. piwil1:pirna complexes", "mature pirna. piwil1:pirna complexes appear", "pirna. piwil1:pirna complexes appear to", "piwil1:pirna complexes appear to be", "complexes appear to be involved", "appear to be involved in", "to be involved in post", "be involved in post transcriptional", "involved in post transcriptional silencing", "in post transcriptional silencing in", "post transcriptional silencing in the", "transcriptional silencing in the cytosol", "silencing in the cytosol while", "in the cytosol while piwil2:pirna", "the cytosol while piwil2:pirna complexes", "cytosol while piwil2:pirna complexes generate", "while piwil2:pirna complexes generate further", "piwil2:pirna complexes generate further pirnas", "complexes generate further pirnas from", "generate further pirnas from transposon", "further pirnas from transposon transcripts", "pirnas from transposon transcripts and", "from transposon transcripts and other", "transposon transcripts and other transcripts", "transcripts and other transcripts in", "and other transcripts in the", "other transcripts in the cytosol.", "transcripts in the cytosol. cleavage", "in the cytosol. cleavage products", "the cytosol. cleavage products from", "cytosol. cleavage products from piwil2:pirna", "cleavage products from piwil2:pirna may", "products from piwil2:pirna may be", "from piwil2:pirna may be loaded", "piwil2:pirna may be loaded into", "may be loaded into either", "be loaded into either piwil2", "loaded into either piwil2 or", "into either piwil2 or piwil4", "piwil2 or piwil4 hiwi2", "piwil4 hiwi2 miwi2", "hiwi2 miwi2 . loading", "miwi2 . loading into piwil2", ". loading into piwil2 forms", "loading into piwil2 forms a", "into piwil2 forms a step", "piwil2 forms a step in", "forms a step in a", "a step in a cytosolic", "step in a cytosolic amplification", "in a cytosolic amplification loop", "a cytosolic amplification loop called", "cytosolic amplification loop called the", "amplification loop called the \\ping", "loop called the \\ping pong", "called the \\ping pong cycle\\", "the \\ping pong cycle\\ which", "\\ping pong cycle\\ which yields", "pong cycle\\ which yields further", "cycle\\ which yields further piwil2:pirna", "which yields further piwil2:pirna complexes", "yields further piwil2:pirna complexes from", "further piwil2:pirna complexes from cleaved", "piwil2:pirna complexes from cleaved precursor", "complexes from cleaved precursor rnas.", "from cleaved precursor rnas. loading", "cleaved precursor rnas. loading into", "precursor rnas. loading into piwil4", "rnas. loading into piwil4 yields", "loading into piwil4 yields a", "into piwil4 yields a complex", "piwil4 yields a complex also", "yields a complex also containing", "a complex also containing tdrd9", "complex also containing tdrd9 that", "also containing tdrd9 that translocates", "containing tdrd9 that translocates to", "tdrd9 that translocates to the", "that translocates to the nucleus", "translocates to the nucleus and", "to the nucleus and directs", "the nucleus and directs dna", "nucleus and directs dna methylation", "and directs dna methylation of", "directs dna methylation of cognate", "dna methylation of cognate loci", "of cognate loci causing", "cognate loci causing transcriptional", "loci causing transcriptional silencing", "causing transcriptional silencing during spermatogenesis.", "transcriptional silencing during spermatogenesis. transcriptional", "silencing during spermatogenesis. transcriptional silencing", "during spermatogenesis. transcriptional silencing by", "spermatogenesis. transcriptional silencing by pirnas", "transcriptional silencing by pirnas is", "silencing by pirnas is necessary", "by pirnas is necessary to", "pirnas is necessary to limit", "is necessary to limit transposition", "necessary to limit transposition of", "to limit transposition of endogenous", "limit transposition of endogenous transposons", "transposition of endogenous transposons such", "of endogenous transposons such as", "endogenous transposons such as l1", "transposons such as l1 elements", "such as l1 elements in", "as l1 elements in the", "l1 elements in the genome." ] }, { "record_id": "GLY_000594_1_725", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "110056", "r hsa", "hsa 110056", "r hsa 110056" ] }, { "record_id": "GLY_000594_1_725", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mapk3 erk1", "erk1 activation", "mapk3 erk1 activation", "mitogen activated", "activated protein", "protein kinase", "kinase kinase", "kinase map2k1", "also known", "known as", "as mek1", "is a", "a dual", "dual threonine", "threonine and", "and tyrosine", "tyrosine recognition", "recognition kinase", "kinase that", "that phosphorylates", "phosphorylates and", "and activates", "activates mapk3", "ohren et", "et al.", "al. 2004", "roskoski 2012a", "2012a .", "mitogen activated protein", "activated protein kinase", "protein kinase kinase", "kinase kinase map2k1", "map2k1 also", "also known as", "known as mek1", "mek1 is", "is a dual", "a dual threonine", "dual threonine and", "threonine and tyrosine", "and tyrosine recognition", "tyrosine recognition kinase", "recognition kinase that", "kinase that phosphorylates", "that phosphorylates and", "phosphorylates and activates", "and activates mapk3", "ohren et al.", "et al. 2004", "2004 roskoski", "roskoski 2012a .", "mitogen activated protein kinase", "activated protein kinase kinase", "protein kinase kinase map2k1", "kinase map2k1 also", "map2k1 also known", "also known as mek1", "as mek1 is", "mek1 is a", "is a dual threonine", "a dual threonine and", "dual threonine and tyrosine", "threonine and tyrosine recognition", "and tyrosine recognition kinase", "tyrosine recognition kinase that", "recognition kinase that phosphorylates", "kinase that phosphorylates and", "that phosphorylates and activates", "phosphorylates and activates mapk3", "activates mapk3 erk1", "erk1 ohren", "ohren et al. 2004", "al. 2004 roskoski", "2004 roskoski 2012a", "mitogen activated protein kinase kinase", "activated protein kinase kinase map2k1", "kinase kinase map2k1 also", "kinase map2k1 also known", "map2k1 also known as", "known as mek1 is", "as mek1 is a", "mek1 is a dual", "is a dual threonine and", "a dual threonine and tyrosine", "dual threonine and tyrosine recognition", "threonine and tyrosine recognition kinase", "and tyrosine recognition kinase that", "tyrosine recognition kinase that phosphorylates", "recognition kinase that phosphorylates and", "kinase that phosphorylates and activates", "that phosphorylates and activates mapk3", "and activates mapk3 erk1", "erk1 ohren et", "et al. 2004 roskoski", "al. 2004 roskoski 2012a", "2004 roskoski 2012a ." ] }, { "record_id": "GLY_000594_1_726", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "110312", "r hsa", "hsa 110312", "r hsa 110312" ] }, 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in", ".

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"il1beta signaling pathways", "pathways gantke", "gantke t et", "et al. 2011", "al. 2011 .

in", "2011 .

in response", ".

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leading to", "leading to changes", "to changes in", "changes in gene", "in gene expression", "expression zuber", "zuber j et", "et al. 2000", "al. 2000 .", "depending upon the stimulus", "upon the stimulus and", "the stimulus and cell", "stimulus and cell type", "and cell type mitogen", "cell type mitogen activated", "type mitogen activated protein", "mitogen activated protein kinases", "protein kinases mapk", "mapk signaling pathway", "signaling pathway can transmit", "pathway can transmit signals", "can transmit signals to", "transmit signals to regulate", "signals to regulate many", "to regulate many different", "regulate many different biological", "many different biological processes", "different biological processes by", "biological processes by virtue", "processes by virtue of", "by virtue of their", "virtue of their ability", "of their ability to", "their ability to target", "ability to target multiple", "to target multiple effector", "target multiple effector proteins", "effector proteins kyriakis", "proteins kyriakis jm", "kyriakis jm & avruch", "jm & avruch j", "& avruch j 2012", "j 2012 yoon", "2012 yoon and", "yoon and seger 2006", "seger 2006 shaul", "2006 shaul yd", "shaul yd & seger", "yd & seger r", "& seger r 2007", "r 2007 arthur", "2007 arthur js", "arthur js & ley", "js & ley sc", "& ley sc 2013", "ley sc 2013 .", "sc 2013 . in", "2013 . in particular", "in particular the", "particular the extracellular", "the extracellular signal regulated", "extracellular signal regulated kinases", "signal regulated kinases mapk3", "regulated kinases mapk3 erk1", "mapk3 erk1 and", "erk1 and mapk1", "and mapk1 erk2", "erk2 are involved", "are involved in diverse", "involved in diverse cellular", "in diverse cellular processes", "diverse cellular processes such", "cellular processes such as", "processes such as proliferation", "as proliferation differentiation", "differentiation regulation of", "regulation of inflammatory responses", "inflammatory responses cytoskeletal", "responses cytoskeletal remodeling", "cytoskeletal remodeling cell", "remodeling cell motility", "cell motility and invasion", "motility and invasion through", "and invasion through the", "invasion through the increase", "through the increase of", "the increase of matrix", "increase of matrix metalloproteinase", "of matrix metalloproteinase production", "metalloproteinase production viala", "production viala e", "viala e & pouyssegur", "e & pouyssegur j", "& pouyssegur j 2004", "j 2004 hsu", "2004 hsu mc", "hsu mc et al.", "mc et al. 2006", "al. 2006 dawson", "2006 dawson cw", "dawson cw et al.2008", "et al.2008 kuriakose", "al.2008 kuriakose t", "kuriakose t et al.", "t et al. 2014", "et al. 2014 .the", "al. 2014 .the canonical", "2014 .the canonical raf:map2k:mapk1/3", ".the canonical raf:map2k:mapk1/3 cascade", "canonical raf:map2k:mapk1/3 cascade is", "raf:map2k:mapk1/3 cascade is stimulated", "cascade is stimulated by", "is stimulated by various", "stimulated by various extracellular", "by various extracellular stimuli", "various extracellular stimuli including", "extracellular stimuli including hormones", "including hormones cytokines", "cytokines growth factors", "growth factors heat", "factors heat shock", "heat shock and uv", "shock and uv irradiation", "and uv irradiation triggering", "uv irradiation triggering the", "irradiation triggering the gef", "triggering the gef mediated", "the gef mediated activation", "gef mediated activation of", "mediated activation of ras", "activation of ras at", "of ras at the", "ras at the plasma", "at the plasma membrane", "the plasma membrane and", "plasma membrane and leading", "membrane and leading to", "and leading to the", "leading to the activation", "to the activation of", "the activation of the", "activation of the raf", "of the raf map3", "the raf map3 kinases.", "raf map3 kinases. however", "kinases. however many", "however many physiological", "many physiological and pathological", "physiological and pathological stimuli", "and pathological stimuli have", "pathological stimuli have been", "stimuli have been found", "have been found to", "been found to activate", "found to activate mapk1/3", "to activate mapk1/3 independently", "activate mapk1/3 independently of", "mapk1/3 independently of raf", "independently of raf and", "of raf and ras", "and ras dawson", "ras dawson cw", "dawson cw et al.", "cw et al. 2008", "al. 2008 wang", "2008 wang j", "wang j et al.", "j et al. 2009", "al. 2009 kuriakose", "2009 kuriakose t", "et al. 2014 .", "al. 2014 . for", "2014 . for example", "for example amp", "example amp activated", "amp activated protein kinase", "protein kinase ampk", "ampk but", "not raf1 was", "raf1 was reported", "was reported to regulate", "reported to regulate map2k1/2", "to regulate map2k1/2 and", "regulate map2k1/2 and mapk1/3", "and mapk1/3 mek", "mapk1/3 mek and", "and erk activation", "erk activation in", "activation in rat hepatoma", "in rat hepatoma h4iie", "rat hepatoma h4iie and", "hepatoma h4iie and human", "h4iie and human erythroleukemia", "and human erythroleukemia k562", "human erythroleukemia k562 cells", "erythroleukemia k562 cells in", "k562 cells in response", "cells in response to", "in response to autophagy", "response to autophagy stimuli", "autophagy stimuli wang", "stimuli wang j", "et al. 2009 .", "al. 2009 . tumor", "2009 . tumor progression", ". tumor progression locus", "tumor progression locus 2", "locus 2 tpl2", "tpl2 also known", "also known as map3k8", "known as map3k8 and", "as map3k8 and cot", "and cot is", "cot is another", "is another map3 kinase", "another map3 kinase which", "map3 kinase which promotes", "kinase which promotes mapk1/3", "promotes mapk1/3 erk", "erk regulated immune", "regulated immune responses downstream", "immune responses downstream of", "responses downstream of toll", "downstream of toll like", "of toll like receptors", "like receptors tlr", "tlr tnf", "tnf receptor and il1beta", "receptor and il1beta signaling", "and il1beta signaling pathways", "signaling pathways gantke", "pathways gantke t", "gantke t et al.", "t et al. 2011", "et al. 2011 .

in", "al. 2011 .

in response", "2011 .

in response to", ".

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activities of an", "activities of an ever", "of an ever growing", "an ever growing pool", "ever growing pool of", "growing pool of substrates", "pool of substrates that", "of substrates that are", "substrates that are estimated", "that are estimated to", "are estimated to comprise", "estimated to comprise over", "to comprise over 160", "comprise over 160 proteins", "160 proteins yoon", "proteins yoon and", "and seger 2006 .", "seger 2006 . the", "2006 . the majority", ". the majority of", "the majority of erk", "majority of erk substrates", "of erk substrates are", "erk substrates are nuclear", "substrates are nuclear proteins", "nuclear proteins but", "proteins but others", "but others are found", "others are found in", "are found in the", "found in the cytoplasm", "in the cytoplasm and", "the cytoplasm and other", "cytoplasm and other organelles.", "and other organelles. activated", "other organelles. activated mapk1/3", "organelles. activated mapk1/3 can", "activated mapk1/3 can translocate", "mapk1/3 can translocate to", "can translocate to the", "translocate to the nucleus", "the nucleus where", "nucleus where they", "where they phosphorylate and", "they phosphorylate and regulate", "phosphorylate and regulate various", "and regulate various transcription", "regulate various transcription factors", "transcription factors such", "factors such as", "such as ets family", "as ets family transcription", "ets family transcription factors", "transcription factors e.g.", "elk1 ultimately", "ultimately leading to changes", "leading to changes in", "to changes in gene", "changes in gene expression", "gene expression zuber", "expression zuber j", "zuber j et al.", "j et al. 2000", "et al. 2000 .", "depending upon the stimulus and", "upon the stimulus and cell", "the stimulus and cell type", "stimulus and cell type mitogen", "and cell type mitogen activated", "cell type mitogen activated protein", "type mitogen activated protein kinases", "activated protein kinases mapk", "kinases mapk signaling", "mapk signaling pathway can", "signaling pathway can transmit signals", "pathway can transmit signals to", "can transmit signals to regulate", "transmit signals to regulate many", "signals to regulate many different", "to regulate many different biological", "regulate many different biological processes", "many different biological processes by", "different biological processes by virtue", "biological processes by virtue of", "processes by virtue of their", "by virtue of their ability", "virtue of their ability to", "of their ability to target", "their ability to target multiple", "ability to target multiple effector", "to target multiple effector proteins", "multiple effector proteins kyriakis", "effector proteins kyriakis jm", "proteins kyriakis jm &", "kyriakis jm & avruch j", "jm & avruch j 2012", "avruch j 2012 yoon", "j 2012 yoon and", "2012 yoon and seger", "and seger 2006 shaul", "seger 2006 shaul yd", "2006 shaul yd &", "shaul yd & seger r", "yd & seger r 2007", "seger r 2007 arthur", "r 2007 arthur js", "2007 arthur js &", "arthur js & ley sc", "js & ley sc 2013", "& ley sc 2013 .", "ley sc 2013 . in", "sc 2013 . in particular", ". in particular the", "in particular the extracellular", "particular the extracellular signal", "the extracellular signal regulated kinases", "extracellular signal regulated kinases mapk3", "signal regulated kinases mapk3 erk1", "kinases mapk3 erk1 and", "mapk3 erk1 and mapk1", "mapk1 erk2 are", "erk2 are involved in", "are involved in diverse cellular", "involved in diverse cellular processes", "in diverse cellular processes such", "diverse cellular processes such as", "cellular processes such as proliferation", "such as proliferation differentiation", "proliferation differentiation regulation", "differentiation regulation of inflammatory", "of inflammatory responses cytoskeletal", "inflammatory responses cytoskeletal remodeling", "cytoskeletal remodeling cell motility", "remodeling cell motility and", "cell motility and invasion through", "motility and invasion through the", "and invasion through the increase", "invasion through the increase of", "through the increase of matrix", "the increase of matrix metalloproteinase", "increase of matrix metalloproteinase production", "matrix metalloproteinase production viala", "metalloproteinase production viala e", "production viala e &", "viala e & pouyssegur j", "e & pouyssegur j 2004", "pouyssegur j 2004 hsu", "j 2004 hsu mc", "2004 hsu mc et", "hsu mc et al. 2006", "et al. 2006 dawson", "al. 2006 dawson cw", "2006 dawson cw et", "cw et al.2008 kuriakose", "et al.2008 kuriakose t", "al.2008 kuriakose t et", "kuriakose t et al. 2014", "t et al. 2014 .the", "et al. 2014 .the canonical", "al. 2014 .the canonical raf:map2k:mapk1/3", "2014 .the canonical raf:map2k:mapk1/3 cascade", ".the canonical raf:map2k:mapk1/3 cascade is", "canonical raf:map2k:mapk1/3 cascade is stimulated", "raf:map2k:mapk1/3 cascade is stimulated by", "cascade is stimulated by various", "is stimulated by various extracellular", "stimulated by various extracellular stimuli", "by various extracellular stimuli including", "various extracellular stimuli including hormones", "stimuli including hormones cytokines", "hormones cytokines growth", "growth factors heat shock", "factors heat shock and", "heat shock and uv irradiation", "shock and uv irradiation triggering", "and uv irradiation triggering the", "uv irradiation triggering the gef", "irradiation triggering the gef mediated", "triggering the gef mediated activation", "the gef mediated activation of", "gef mediated activation of ras", "mediated activation of ras at", "activation of ras at the", "of ras at the plasma", "ras at the plasma membrane", "at the plasma membrane and", "the plasma membrane and leading", "plasma membrane and leading to", "membrane and leading to the", "and leading to the activation", "leading to the activation of", "to the activation of the", "the activation of the raf", "activation of the raf map3", "of the raf map3 kinases.", "the raf map3 kinases. however", "map3 kinases. however many", "kinases. however many physiological", "however many physiological and", "many physiological and pathological stimuli", "physiological and pathological stimuli have", "and pathological stimuli have been", "pathological stimuli have been found", "stimuli have been found to", "have been found to activate", "been found to activate mapk1/3", "found to activate mapk1/3 independently", "to activate mapk1/3 independently of", "activate mapk1/3 independently of raf", "mapk1/3 independently of raf and", "independently of raf and ras", "raf and ras dawson", "and ras dawson cw", "ras dawson cw et", "dawson cw et al. 2008", "et al. 2008 wang", "al. 2008 wang j", "2008 wang j et", "wang j et al. 2009", "et al. 2009 kuriakose", "al. 2009 kuriakose t", "2009 kuriakose t et", "t et al. 2014 .", "et al. 2014 . for", "al. 2014 . for example", ". for example amp", "for 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tumor progression locus", ". tumor progression locus 2", "progression locus 2 tpl2", "2 tpl2 also", "tpl2 also known as", "also known as map3k8 and", "known as map3k8 and cot", "map3k8 and cot is", "and cot is another", "cot is another map3", "is another map3 kinase which", "another map3 kinase which promotes", "map3 kinase which promotes mapk1/3", "which promotes mapk1/3 erk", "mapk1/3 erk regulated", "erk regulated immune responses", "regulated immune responses downstream of", "immune responses downstream of toll", "responses downstream of toll like", "downstream of toll like receptors", "toll like receptors tlr", "tlr tnf receptor", "tnf receptor and il1beta signaling", "receptor and il1beta signaling pathways", "il1beta signaling pathways gantke", "signaling pathways gantke t", "pathways gantke t et", "gantke t et al. 2011", "t et al. 2011 .

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"varied functions", "bole feysot", "feysot et", "et al.", "al. 1998", "1998 .", ". despite", "despite this", "few pathologies", "pathologies have", "have been", "been associated", "associated with", "with abnormalities", "abnormalities in", "in prolactin", "though roles", "roles in", "in various", "various forms", "forms of", "of cancer", "cancer and", "and certain", "certain autoimmune", "autoimmune disorders", "disorders have", "been suggested", "goffin et", "al. 2002", "2002 .", ". a", "a vast", "vast body", "body of", "of literature", "literature suggests", "suggests effects", "effects of", "of prl", "prl in", "in immune", "immune cells", "matera 1996", "but prlr", "prlr ko", "ko mice", "mice have", "have unaltered", "unaltered immune", "immune system", "system development", "development and", "and function", "bouchard et", "al. 1999", "1999 .", ". in", "in addition", "addition to", "to the", "the pituitary", "numerous other", "other tissues", "tissues produce", "produce prl", "including the", "the decidua", "decidua and", "and myometrium", "certain cells", "cells of", "the immune", "skin and", "and exocrine", "exocrine glands", "glands such", "such as", "as the", "sweat and", "and lacrimal", "lacrimal glands", "ben jonathan", "jonathan et", "al. 1996", "1996 .", ". pituitary", "pituitary prl", "prl secretion", "secretion is", "is negatively", "negatively regulated", "regulated by", "by inhibitory", "inhibitory factors", "factors originating", "originating from", "from the", "the hypothalamus", "the most", "most important", "important of", "of which", "which is", "is dopamine", "acting through", "through the", "the d2", "d2 subclass", "subclass of", "of dopamine", "dopamine receptors", "receptors present", "present in", "in lactotrophs", "freeman et", "al. 2000", "2000 .", ". prl", "prl binding", "binding sites", "sites or", "or receptors", "receptors have", "been identified", "identified in", "in numerous", "numerous cells", "cells and", "and tissues", "tissues of", "of adult", "adult mammals.", "mammals. various", "of prlr", "generated by", "by alternative", "alternative splicing", "been reported", "reported in", "in several", "several species", "species including", "including humans", "kelly et", "al. 1991", "clevenger et", "al. 2003", "2003 .

prlr", ".

prlr is", "a member", "member of", "the cytokine", "cytokine receptor", "receptor superfamily.", "superfamily. like", "like many", "many other", "other members", "members of", "of this", "this family", "the first", "first step", "step in", "in receptor", "receptor activation", "activation was", "was generally", "generally believed", "believed to", "to be", "be ligand", "ligand induced", "induced dimerization", "dimerization whereby", "whereby one", "one molecule", "molecule of", "prl bound", "bound to", "to two", "two molecules", "molecules of", "of receptor", "elkins et", ". recent", "recent reports", "reports suggest", "suggest that", "that prlr", "prlr pre", "pre assembles", "assembles at", "at the", "the plasma", "plasma membrane", "membrane in", "in the", "the absence", "absence of", "of ligand", "gadd &", "& clevenger", "clevenger 2006", "tallet et", "al. 2011", "suggesting that", "that ligand", "induced activation", "activation involves", "involves conformational", "conformational changes", "changes in", "in preformed", "preformed prlr", "prlr dimers", "broutin et", "al. 2010", "2010 .", ".

prlr", "

prlr has", "has no", "no intrinsic", "intrinsic kinase", "kinase activity", "activity but", "but associates", "lebrun et", "al. 1994", "with janus", "janus kinase", "kinase 2", "is activated", "activated following", "following receptor", "campbell et", "rui et", "carter su", "su et", "barua et", "al. 2009", "2009 .", ". jak2", "jak2 dependent", "dependent activation", "activation of", "of jak1", "jak1 has", "has also", "also been", "neilson et", "al. 2007", "2007 .", ". it", "it is", "is generally", "generally accepted", "accepted that", "that activation", "of jak2", "jak2 occurs", "occurs by", "by transphosphorylation", "transphosphorylation upon", "upon ligand", "induced receptor", "based on", "on jak", "jak activation", "activation by", "by chimeric", "chimeric receptors", "receptors in", "in which", "which various", "various extracellular", "extracellular domains", "domains of", "of cytokine", "cytokine or", "or tyrosine", "tyrosine kinase", "kinase receptors", "receptors were", "were fused", "fused to", "the il", "il 2", "2 receptor", "receptor beta", "beta chain", "see ihle", "ihle et", "1994 .", ". this", "this activation", "activation step", "step involves", "involves the", "the tyrosine", "tyrosine phosphorylation", "phosphorylation of", "which in", "in turn", "turn phosphorylates", "phosphorylates prlr", "prlr on", "on specific", "specific intracellular", "intracellular tyrosine", "tyrosine residues", "residues leading", "leading to", "to stat5", "stat5 recruitment", "recruitment and", "and signaling", "considered to", "be the", "important signaling", "signaling cascade", "cascade for", "for prlr.", "prlr. stat1", "stat1 and", "and stat3", "stat3 activation", "activation have", "have also", "dasilva et", "as have", "have many", "other signaling", "signaling pathways", "signaling through", "through map", "map kinases", "has been", "reported as", "as a", "a consequence", "consequence of", "prl stimuilation", "stimuilation in", "in many", "many different", "different cellular", "cellular systems", "see bole", "though it", "is not", "not clear", "clear how", "how this", "this signal", "signal is", "is propagated.", "propagated. other", "other cascades", "cascades non", "non exhaustively", "exhaustively include", "include src", "src kinases", "focal adhesion", "adhesion kinase", "phospholipase c", "c gamma", "pi3 kinase/akt", "kinase/akt and", "and nek3", "miller et", ". the", "the protein", "protein tyrosine", "tyrosine phosphatase", "phosphatase shp2", "shp2 is", "is recruited", "recruited to", "the c", "c terminal", "terminal tyrosine", "tyrosine of", "prlr and", "and may", "may have", "have a", "a regulatory", "regulatory role", "ali &", "& ali", "ali 2000", ". prlr", "prlr phosphotyrosines", "phosphotyrosines can", "can recruit", "recruit insulin", "insulin receptor", "receptor substrates", "and other", "other adaptor", "adaptor proteins", "proteins to", "the receptor", "receptor complex", "1998 .

female", ".

female homozygous", "homozygous prlr", "prlr knockout", "knockout mice", "mice are", "are completely", "completely infertile", "infertile and", "and show", "show a", "a lack", "lack of", "of mammary", "mammary development", "ormandy et", "al. 1997", "1997 .", ". hemizogotes", "hemizogotes are", "are unable", "unable to", "to lactate", "lactate following", "following their", "their first", "first pregnancy", "pregnancy and", "and depending", "depending on", "on the", "the genetic", "genetic background", "this phenotype", "phenotype can", "can persist", "persist through", "through subsequent", "subsequent pregnancies", "al. 2001", "2001 .", "prolactin prl", "prl is", "is a hormone", "a hormone secreted", "hormone secreted mainly", "secreted mainly by", "mainly by the", "by the anterior", "the anterior pituitary", "anterior pituitary gland.", "pituitary gland. it", "gland. it was", "it was originally", "was originally identified", "originally identified by", "identified by its", "by its ability", "its ability to", "ability to stimulate", "to stimulate the", "stimulate the development", "the development of", "development of the", "of the mammary", "the mammary gland", "mammary gland and", "gland and lactation", "lactation but", "but is now", "is now known", "now known to", "known to have", "to have numerous", "have numerous and", "numerous and varied", "and varied functions", "functions bole", "bole feysot et", "feysot et al.", "et al. 1998", "al. 1998 .", "1998 . despite", ". despite this", "this few", "few pathologies have", "pathologies have been", "have been associated", "been associated with", "associated with abnormalities", "with abnormalities in", "abnormalities in prolactin", "in prolactin receptor", "receptor prlr", "prlr signaling", "signaling though", "though roles in", "roles in various", "in various forms", "various forms of", "forms of cancer", "of cancer and", "cancer and certain", "and certain autoimmune", "certain autoimmune disorders", "autoimmune disorders have", "disorders have been", "have been suggested", "suggested goffin", "goffin et al.", "et al. 2002", "al. 2002 .", "2002 . a", ". a vast", "a vast body", "vast body of", "body of literature", "of literature suggests", "literature suggests effects", "suggests effects of", "effects of prl", "of prl in", "prl in immune", "in immune cells", "cells matera", "1996 but", "but prlr ko", "prlr ko mice", "ko mice have", "mice have unaltered", "have unaltered immune", "unaltered immune system", "immune system development", "system development and", "development and function", "function bouchard", "bouchard et al.", "et al. 1999", "al. 1999 .", "1999 . in", ". in addition", "in addition to", "addition to the", "to the pituitary", "pituitary numerous", "numerous other tissues", "other tissues produce", "tissues produce prl", "prl including", "including the decidua", "the decidua and", "decidua and myometrium", "myometrium certain", "certain cells of", "cells of the", "of the immune", "the immune system", "system brain", "brain skin", "skin and exocrine", "and exocrine glands", "exocrine glands such", "glands such as", "such as the", "as the mammary", "mammary sweat", "sweat and lacrimal", "and lacrimal glands", "glands ben", "ben jonathan et", "jonathan et al.", "et al. 1996", "al. 1996 .", "1996 . pituitary", ". pituitary prl", "pituitary prl secretion", "prl secretion is", "secretion is negatively", "is negatively regulated", "negatively regulated by", "regulated by inhibitory", "by inhibitory factors", "inhibitory factors originating", "factors originating from", "originating from the", "from the hypothalamus", "hypothalamus the", "the most important", "most important of", "important of which", "of which is", "which is dopamine", "dopamine acting", "acting through the", "through the d2", "the d2 subclass", "d2 subclass of", "subclass of dopamine", "of dopamine receptors", "dopamine receptors present", "receptors present in", "present in lactotrophs", "lactotrophs freeman", "freeman et al.", "et al. 2000", "al. 2000 .", "2000 . prl", ". prl binding", "prl binding sites", "binding sites or", "sites or receptors", "or receptors have", "receptors have been", "have been identified", "been identified in", "identified in numerous", "in numerous cells", "numerous cells and", "cells and tissues", "and tissues of", "tissues of adult", "of adult mammals.", "adult mammals. various", "mammals. various forms", "forms of prlr", "prlr generated", "generated by alternative", "by alternative splicing", "splicing have", "have been reported", "been reported in", "reported in several", "in several species", "several species including", "species including humans", "humans kelly", "kelly et al.", "et al. 1991", "1991 clevenger", "clevenger et al.", "et al. 2003", "al. 2003 .

prlr", "2003 .

prlr is", ".

prlr is a", "is a member", "a member of", "member of the", "of the cytokine", "the cytokine receptor", "cytokine receptor superfamily.", "receptor superfamily. like", "superfamily. like many", "like many other", "many other members", "other members of", "members of this", "of this family", "family the", "the first step", "first step in", "step in receptor", "in receptor activation", "receptor activation was", "activation was generally", "was generally believed", "generally believed to", "believed to be", "to be ligand", "be ligand induced", "ligand induced dimerization", "induced dimerization whereby", "dimerization whereby one", "whereby one molecule", "one molecule of", "molecule of prl", "of prl bound", "prl bound to", "bound to two", "to two molecules", "two molecules of", "molecules of receptor", "receptor elkins", "elkins et al.", "2000 . recent", ". recent reports", "recent reports suggest", "reports suggest that", "suggest that prlr", "that prlr pre", "prlr pre assembles", "pre assembles at", "assembles at the", "at the plasma", "the plasma membrane", "plasma membrane in", "membrane in the", "in the absence", "the absence of", "absence of ligand", "ligand gadd", "gadd & clevenger", "& clevenger 2006", "2006 tallet", "tallet et al.", "et al. 2011", "suggesting that ligand", "that ligand induced", "ligand induced activation", "induced activation involves", "activation involves conformational", "involves conformational changes", "conformational changes in", "changes in preformed", "in preformed prlr", "preformed prlr dimers", "dimers broutin", "broutin et al.", "et al. 2010", "al. 2010 .", "2010 .

prlr", ".

prlr has", "

prlr has no", "has no intrinsic", "no intrinsic kinase", "intrinsic kinase activity", "kinase activity but", "activity but associates", "associates lebrun", "lebrun et al.", "et al. 1994", "1994 1995", "1995 with", "with janus kinase", "janus kinase 2", "2 jak2", "jak2 which", "which is activated", "is activated following", "activated following receptor", "following receptor activation", "activation campbell", "campbell et al.", "1994 rui", "rui et al.", "1994 carter", "carter su et", "su et al.", "2000 barua", "barua et al.", "et al. 2009", "al. 2009 .", "2009 . jak2", ". jak2 dependent", "jak2 dependent activation", "dependent activation of", "activation of jak1", "of jak1 has", "jak1 has also", "has also been", "also been reported", "reported neilson", "neilson et al.", "et al. 2007", "al. 2007 .", "2007 . it", ". it is", "it is generally", "is generally accepted", "generally accepted that", "accepted that activation", "that activation of", "activation of jak2", "of jak2 occurs", "jak2 occurs by", "occurs by transphosphorylation", "by transphosphorylation upon", "transphosphorylation upon ligand", "upon ligand induced", "ligand induced receptor", "induced receptor activation", "activation based", "based on jak", "on jak activation", "jak activation by", "activation by chimeric", "by chimeric receptors", "chimeric receptors in", "receptors in which", "in which various", "which various extracellular", "various extracellular domains", "extracellular domains of", "domains of cytokine", "of cytokine or", "cytokine or tyrosine", "or tyrosine kinase", "tyrosine kinase receptors", "kinase receptors were", "receptors were fused", "were fused to", "fused to the", "to the il", "the il 2", "il 2 receptor", "2 receptor beta", "receptor beta chain", "chain see", "see ihle et", "ihle et al.", "al. 1994 .", "1994 . this", ". this activation", "this activation step", "activation step involves", "step involves the", "involves the tyrosine", "the tyrosine phosphorylation", "tyrosine phosphorylation of", "phosphorylation of jak2", "which in turn", "in turn phosphorylates", "turn phosphorylates prlr", "phosphorylates prlr on", "prlr on specific", "on specific intracellular", "specific intracellular tyrosine", "intracellular tyrosine residues", "tyrosine residues leading", "residues leading to", "leading to stat5", "to stat5 recruitment", "stat5 recruitment and", "recruitment and signaling", "signaling considered", "considered to be", "to be the", "be the most", "most important signaling", "important signaling cascade", "signaling cascade for", "cascade for prlr.", "for prlr. stat1", "prlr. stat1 and", "stat1 and stat3", "and stat3 activation", "stat3 activation have", "activation have also", "have also been", "reported dasilva", "dasilva et al.", "1996 as", "as have many", "have many other", "many other signaling", "other signaling pathways", "pathways signaling", "signaling through map", "through map kinases", "kinases shc/sos/grb2/ras/raf/mapk", "shc/sos/grb2/ras/raf/mapk has", "has been reported", "been reported as", "reported as a", "as a consequence", "a consequence of", "consequence of prl", "of prl stimuilation", "prl stimuilation in", "stimuilation in many", "in many different", "many different cellular", "different cellular systems", "systems see", "see bole feysot", "1998 though", "though it is", "it is not", "is not clear", "not clear how", "clear how this", "how this signal", "this signal is", "signal is propagated.", "is propagated. other", "propagated. other cascades", "other cascades non", "cascades non exhaustively", "non exhaustively include", "exhaustively include src", "include src kinases", "kinases focal", "focal adhesion kinase", "kinase phospholipase", "phospholipase c gamma", "gamma pi3", "pi3 kinase/akt and", "kinase/akt and nek3", "nek3 clevenger", "2003 miller", "miller et al.", "2007 . the", ". the protein", "the protein tyrosine", "protein tyrosine phosphatase", "tyrosine phosphatase shp2", "phosphatase shp2 is", "shp2 is recruited", "is recruited to", "recruited to the", "to the c", "the c terminal", "c terminal tyrosine", "terminal tyrosine of", "tyrosine of prlr", "of prlr and", "prlr and may", "and may have", "may have a", "have a regulatory", "a regulatory role", "role ali", "ali & ali", "& ali 2000", "ali 2000 .", "2000 . prlr", ". prlr phosphotyrosines", "prlr phosphotyrosines can", "phosphotyrosines can recruit", "can recruit insulin", "recruit insulin receptor", "insulin receptor substrates", "substrates irs", "irs and", "and other adaptor", "other adaptor proteins", "adaptor proteins to", "proteins to the", "to the receptor", "the receptor complex", "complex bole", "al. 1998 .

female", "1998 .

female homozygous", ".

female homozygous prlr", "homozygous prlr knockout", "prlr knockout mice", "knockout mice are", "mice are completely", "are completely infertile", "completely infertile and", "infertile and show", "and show a", "show a lack", "a lack of", "lack of mammary", "of mammary development", "development ormandy", "ormandy et al.", "et al. 1997", "al. 1997 .", "1997 . hemizogotes", ". hemizogotes are", "hemizogotes are unable", "are unable to", "unable to lactate", "to lactate following", "lactate following their", "following their first", "their first pregnancy", "first pregnancy and", "pregnancy and depending", "and depending on", "depending on the", "on the genetic", "the genetic background", "background this", "this phenotype can", "phenotype can persist", "can persist through", "persist through subsequent", "through subsequent pregnancies", "pregnancies kelly", "et al. 2001", "al. 2001 .", "prl is a", "is a hormone secreted", "a hormone secreted mainly", "hormone secreted mainly by", "secreted mainly by the", "mainly by the anterior", "by the anterior pituitary", "the anterior pituitary gland.", "anterior pituitary gland. it", "pituitary gland. it was", "gland. it was originally", "it was originally identified", "was originally identified by", "originally identified by its", "identified by its ability", "by its ability to", "its ability to stimulate", "ability to stimulate the", "to stimulate the development", "stimulate the development of", "the development of the", "development of the mammary", "of the mammary gland", "the mammary gland and", "mammary gland and lactation", "and lactation but", "lactation but is", "but is now known", "is now known to", "now known to have", "known to have numerous", "to have numerous and", "have numerous and varied", "numerous and varied functions", "varied functions bole", "functions bole feysot", "bole feysot et al.", "feysot et al. 1998", "et al. 1998 .", "al. 1998 . despite", "1998 . despite this", "despite this few", "this few pathologies", "few pathologies have been", "pathologies have been associated", "have been associated with", "been associated with abnormalities", "associated with abnormalities in", "with abnormalities in prolactin", "abnormalities in prolactin receptor", "prolactin receptor prlr", "signaling though roles", "though roles in various", "roles in various forms", "in various forms of", "various forms of cancer", "forms of cancer and", "of cancer and certain", "cancer and certain autoimmune", "and certain autoimmune disorders", "certain autoimmune disorders have", "autoimmune disorders have been", "disorders have been suggested", "been suggested goffin", "suggested goffin et", "goffin et al. 2002", "et al. 2002 .", "al. 2002 . a", "2002 . a vast", ". a vast body", "a vast body of", "vast body of literature", "body of literature suggests", "of literature suggests effects", "literature suggests effects of", "suggests effects of prl", "effects of prl in", "of prl in immune", "prl in immune cells", "immune cells matera", "cells matera 1996", "matera 1996 but", "1996 but prlr", "but prlr ko mice", "prlr ko mice have", "ko mice have unaltered", "mice have unaltered immune", "have unaltered immune system", "unaltered immune system development", "immune system development and", "system development and function", "and function bouchard", "function bouchard et", "bouchard et al. 1999", "et al. 1999 .", "al. 1999 . in", "1999 . in addition", ". in addition to", "in addition to the", "addition to the pituitary", "the pituitary numerous", "pituitary numerous other", "numerous other tissues produce", "other tissues produce prl", "produce prl including", "prl including the", "including the decidua and", "the decidua and myometrium", "and myometrium certain", "myometrium certain cells", "certain cells of the", "cells of the immune", "of the immune system", "immune system brain", "brain skin and", "skin and exocrine glands", "and exocrine glands such", "exocrine glands such as", "glands such as the", "such as the mammary", "the mammary sweat", "mammary sweat and", "sweat and lacrimal glands", "lacrimal glands ben", "glands ben jonathan", "ben jonathan et al.", "jonathan et al. 1996", "et al. 1996 .", "al. 1996 . pituitary", "1996 . pituitary prl", ". pituitary prl secretion", "pituitary prl secretion is", "prl secretion is negatively", "secretion is negatively regulated", "is negatively regulated by", "negatively regulated by inhibitory", "regulated by inhibitory factors", "by inhibitory factors originating", "inhibitory factors originating from", "factors originating from the", "originating from the hypothalamus", "the hypothalamus the", "hypothalamus the most", "the most important of", "most important of which", "important of which is", "of which is dopamine", "is dopamine acting", "dopamine acting through", "acting through the d2", "through the d2 subclass", "the d2 subclass of", "d2 subclass of dopamine", "subclass of dopamine receptors", "of dopamine receptors present", "dopamine receptors present in", "receptors present in lactotrophs", "in lactotrophs freeman", "lactotrophs freeman et", "freeman et al. 2000", "et al. 2000 .", "al. 2000 . prl", "2000 . prl binding", ". prl binding sites", "prl binding sites or", "binding sites or receptors", "sites or receptors have", "or receptors have been", "receptors have been identified", "have been identified in", "been identified in numerous", "identified in numerous cells", "in numerous cells and", "numerous cells and tissues", "cells and tissues of", "and tissues of adult", "tissues of adult mammals.", "of adult mammals. various", "adult mammals. various forms", "mammals. various forms of", "various forms of prlr", "of prlr generated", "prlr generated by", "generated by alternative splicing", "alternative splicing have", "splicing have been", "have been reported in", "been reported in several", "reported in several species", "in several species including", "several species including humans", "including humans kelly", "humans kelly et", "kelly et al. 1991", "al. 1991 clevenger", "1991 clevenger et", "clevenger et al. 2003", "et al. 2003 .

prlr", "al. 2003 .

prlr is", "2003 .

prlr is a", ".

prlr is a member", "is a member of", "a member of the", "member of the cytokine", "of the cytokine receptor", "the cytokine receptor superfamily.", "cytokine receptor superfamily. like", "receptor superfamily. like many", "superfamily. like many other", "like many other members", "many other members of", "other members of this", "members of this family", "this family the", "family the first", "the first step in", "first step in receptor", "step in receptor activation", "in receptor activation was", "receptor activation was generally", "activation was generally believed", "was generally believed to", "generally believed to be", "believed to be ligand", "to be ligand induced", "be ligand induced dimerization", "ligand induced dimerization whereby", "induced dimerization whereby one", "dimerization whereby one molecule", "whereby one molecule of", "one molecule of prl", "molecule of prl bound", "of prl bound to", "prl bound to two", "bound to two molecules", "to two molecules of", "two molecules of receptor", "of receptor elkins", "receptor elkins et", "elkins et al. 2000", "al. 2000 . recent", "2000 . recent reports", ". recent reports suggest", "recent reports suggest that", "reports suggest that prlr", "suggest that prlr pre", "that prlr pre assembles", "prlr pre assembles at", "pre assembles at the", "assembles at the plasma", "at the plasma membrane", "the plasma membrane in", "plasma membrane in the", "membrane in the absence", "in the absence of", "the absence of ligand", "of ligand gadd", "ligand gadd &", "gadd & clevenger 2006", "clevenger 2006 tallet", "2006 tallet et", "tallet et al. 2011", "2011 suggesting", "suggesting that ligand induced", "that ligand induced activation", "ligand induced activation involves", "induced activation involves conformational", "activation involves conformational changes", "involves conformational changes in", "conformational changes in preformed", "changes in preformed prlr", "in preformed prlr dimers", "prlr dimers broutin", "dimers broutin et", "broutin et al. 2010", "et al. 2010 .", "al. 2010 .

prlr", "2010 .

prlr has", ".

prlr has no", "

prlr has no intrinsic", "has no intrinsic kinase", "no intrinsic kinase activity", "intrinsic kinase activity but", "kinase activity but associates", "but associates lebrun", "associates lebrun et", "lebrun et al. 1994", "al. 1994 1995", "1995 with janus", "with janus kinase 2", "kinase 2 jak2", "jak2 which is", "which is activated following", "is activated following receptor", "activated following receptor activation", "receptor activation campbell", "activation campbell et", "campbell et al. 1994", "al. 1994 rui", "1994 rui et", "rui et al. 1994", "al. 1994 carter", "1994 carter su", "carter su et al.", "su et al. 2000", "al. 2000 barua", "2000 barua et", "barua et al. 2009", "et al. 2009 .", "al. 2009 . jak2", "2009 . jak2 dependent", ". jak2 dependent activation", "jak2 dependent activation of", "dependent activation of jak1", "activation of jak1 has", "of jak1 has also", "jak1 has also been", "has also been reported", "been reported neilson", "reported neilson et", "neilson et al. 2007", "et al. 2007 .", "al. 2007 . it", "2007 . it is", ". it is generally", "it is generally accepted", "is generally accepted that", "generally accepted that activation", "accepted that activation of", "that activation of jak2", "activation of jak2 occurs", "of jak2 occurs by", "jak2 occurs by transphosphorylation", "occurs by transphosphorylation upon", "by transphosphorylation upon ligand", "transphosphorylation upon ligand induced", "upon ligand induced receptor", "ligand induced receptor activation", "receptor activation based", "activation based on", "based on jak activation", "on jak activation by", "jak activation by chimeric", "activation by chimeric receptors", "by chimeric receptors in", "chimeric receptors in which", "receptors in which various", "in which various extracellular", "which various extracellular domains", "various extracellular domains of", "extracellular domains of cytokine", "domains of cytokine or", "of cytokine or tyrosine", "cytokine or tyrosine kinase", "or tyrosine kinase receptors", "tyrosine kinase receptors were", "kinase receptors were fused", "receptors were fused to", "were fused to the", "fused to the il", "to the il 2", "the il 2 receptor", "il 2 receptor beta", "2 receptor beta chain", "beta chain see", "chain see ihle", "see ihle et al.", "ihle et al. 1994", "et al. 1994 .", "al. 1994 . this", "1994 . this activation", ". this activation step", "this activation step involves", "activation step involves the", "step involves the tyrosine", "involves the tyrosine phosphorylation", "the tyrosine phosphorylation of", "tyrosine phosphorylation of jak2", "of jak2 which", "jak2 which in", "which in turn phosphorylates", "in turn phosphorylates prlr", "turn phosphorylates prlr on", "phosphorylates prlr on specific", "prlr on specific intracellular", "on specific intracellular tyrosine", "specific intracellular tyrosine residues", "intracellular tyrosine residues leading", "tyrosine residues leading to", "residues leading to stat5", "leading to stat5 recruitment", "to stat5 recruitment and", "stat5 recruitment and signaling", "and signaling considered", "signaling considered to", "considered to be the", "to be the most", "be the most important", "the most important signaling", "most important signaling cascade", "important signaling cascade for", "signaling cascade for prlr.", "cascade for prlr. stat1", "for prlr. stat1 and", "prlr. stat1 and stat3", "stat1 and stat3 activation", "and stat3 activation have", "stat3 activation have also", "activation have also been", "have also been reported", "been reported dasilva", "reported dasilva et", "dasilva et al. 1996", "al. 1996 as", "1996 as have", "as have many other", "have many other signaling", "many other signaling pathways", "signaling pathways signaling", "pathways signaling through", "signaling through map kinases", "map kinases shc/sos/grb2/ras/raf/mapk", "shc/sos/grb2/ras/raf/mapk has been", "has been reported as", "been reported as a", "reported as a consequence", "as a consequence of", "a consequence of prl", "consequence of prl stimuilation", "of prl stimuilation in", "prl stimuilation in many", "stimuilation in many different", "in many different cellular", "many different cellular systems", "cellular systems see", "systems see bole", "see bole feysot et", "al. 1998 though", "1998 though it", "though it is not", "it is not clear", "is not clear how", "not clear how this", "clear how this signal", "how this signal is", "this signal is propagated.", "signal is propagated. other", "is propagated. other cascades", "propagated. other cascades non", "other cascades non exhaustively", "cascades non exhaustively include", "non exhaustively include src", "exhaustively include src kinases", "src kinases focal", "kinases focal adhesion", "adhesion kinase phospholipase", "kinase phospholipase c", "c gamma pi3", "gamma pi3 kinase/akt", "pi3 kinase/akt and nek3", "and nek3 clevenger", "nek3 clevenger et", "al. 2003 miller", "2003 miller et", "miller et al. 2007", "al. 2007 . the", "2007 . the protein", ". the protein tyrosine", "the protein tyrosine phosphatase", "protein tyrosine phosphatase shp2", "tyrosine phosphatase shp2 is", "phosphatase shp2 is recruited", "shp2 is recruited to", "is recruited to the", "recruited to the c", "to the c terminal", "the c terminal tyrosine", "c terminal tyrosine of", "terminal tyrosine of prlr", "tyrosine of prlr and", "of prlr and may", "prlr and may have", "and may have a", "may have a regulatory", "have a regulatory role", "regulatory role ali", "role ali &", "ali & ali 2000", "& ali 2000 .", "ali 2000 . prlr", "2000 . prlr phosphotyrosines", ". prlr phosphotyrosines can", "prlr phosphotyrosines can recruit", "phosphotyrosines can recruit insulin", "can recruit insulin receptor", "recruit insulin receptor substrates", "receptor substrates irs", "irs and other", "and other adaptor proteins", "other adaptor proteins to", "adaptor proteins to the", "proteins to the receptor", "to the receptor complex", "receptor complex bole", "complex bole feysot", "et al. 1998 .

female", "al. 1998 .

female homozygous", "1998 .

female homozygous prlr", ".

female homozygous prlr knockout", "homozygous prlr knockout mice", "prlr knockout mice are", "knockout mice are completely", "mice are completely infertile", "are completely infertile and", "completely infertile and show", "infertile and show a", "and show a lack", "show a lack of", "a lack of mammary", "lack of mammary development", "mammary development ormandy", "development ormandy et", "ormandy et al. 1997", "et al. 1997 .", "al. 1997 . hemizogotes", "1997 . hemizogotes are", ". hemizogotes are unable", "hemizogotes are unable to", "are unable to lactate", "unable to lactate following", "to lactate following their", "lactate following their first", "following their first pregnancy", "their first pregnancy and", "first pregnancy and depending", "pregnancy and depending on", "and depending on the", "depending on the genetic", "on the genetic background", "genetic background this", "background this phenotype", "this phenotype can persist", "phenotype can persist through", "can persist through subsequent", "persist through subsequent pregnancies", "subsequent pregnancies kelly", "pregnancies kelly et", "kelly et al. 2001", "et al. 2001 .", "prolactin prl is", "prl is a hormone", "is a hormone secreted mainly", "a hormone secreted mainly by", "hormone secreted mainly by the", "secreted mainly by the anterior", "mainly by the anterior pituitary", "by the anterior pituitary gland.", "the anterior pituitary gland. it", "anterior pituitary gland. it was", "pituitary gland. it was originally", "gland. it was originally identified", "it was originally identified by", "was originally identified by its", "originally identified by its ability", "identified by its ability to", "by its ability to stimulate", "its ability to stimulate the", "ability to stimulate the development", "to stimulate the development of", "stimulate the development of the", "the development of the mammary", "development of the mammary gland", "of the mammary gland and", "the mammary gland and lactation", "gland and lactation but", "and lactation but is", "lactation but is now", "but is now known to", "is now known to have", "now known to have numerous", "known to have numerous and", "to have numerous and varied", "have numerous and varied functions", "and varied functions bole", "varied functions bole feysot", "functions bole feysot et", "bole feysot et al. 1998", "feysot et al. 1998 .", "et al. 1998 . despite", "al. 1998 . despite this", ". despite this few", "despite this few pathologies", "this few pathologies have", "few pathologies have been associated", "pathologies have been associated with", "have been associated with abnormalities", "been associated with abnormalities in", "associated with abnormalities in prolactin", "with abnormalities in prolactin receptor", "in prolactin receptor prlr", "receptor prlr signaling", "prlr signaling though", "signaling though roles in", "though roles in various forms", "roles in various forms of", "in various forms of cancer", "various forms of cancer and", "forms of cancer and certain", "of cancer and certain autoimmune", "cancer and certain autoimmune disorders", "and certain autoimmune disorders have", "certain autoimmune disorders have been", "autoimmune disorders have been suggested", "have been suggested goffin", "been suggested goffin et", "suggested goffin et al.", "goffin et al. 2002 .", "et al. 2002 . a", "al. 2002 . a vast", "2002 . a vast body", ". a vast body of", "a vast body of literature", "vast body of literature suggests", "body of literature suggests effects", "of literature suggests effects of", "literature suggests effects of prl", "suggests effects of prl in", "effects of prl in immune", "of prl in immune cells", "in immune cells matera", "immune cells matera 1996", "matera 1996 but prlr", "1996 but prlr ko", "but prlr ko mice have", "prlr ko mice have unaltered", "ko mice have unaltered immune", "mice have unaltered immune system", "have unaltered immune system development", "unaltered immune system development and", "immune system development and function", "development and function bouchard", "and function bouchard et", "function bouchard et al.", "bouchard et al. 1999 .", "et al. 1999 . in", "al. 1999 . in addition", "1999 . in addition to", ". in addition to the", "in addition to the pituitary", "to the pituitary numerous", "the pituitary numerous other", "pituitary numerous other tissues", "numerous other tissues produce prl", "tissues produce prl including", "produce prl including the", "prl including the decidua", "including the decidua and myometrium", "decidua and myometrium certain", "and myometrium certain cells", "myometrium certain cells of", "certain cells of the immune", "cells of the immune system", "the immune system brain", "system brain skin", "brain skin and exocrine", "skin and exocrine glands such", "and exocrine glands such as", "exocrine glands such as the", "glands such as the mammary", "as the mammary sweat", "the mammary sweat and", "mammary sweat and lacrimal", "and lacrimal glands ben", "lacrimal glands ben jonathan", "glands ben jonathan et", "ben jonathan et al. 1996", "jonathan et al. 1996 .", "et al. 1996 . pituitary", "al. 1996 . pituitary prl", "1996 . pituitary prl secretion", ". pituitary prl secretion is", "pituitary prl secretion is negatively", "prl secretion is negatively regulated", "secretion is negatively regulated by", "is negatively regulated by inhibitory", "negatively regulated by inhibitory factors", "regulated by inhibitory factors originating", "by inhibitory factors originating from", "inhibitory factors originating from the", "factors originating from the hypothalamus", "from the hypothalamus the", "the hypothalamus the most", "hypothalamus the most important", "the most important of which", "most important of which is", "important of which is dopamine", "which is dopamine acting", "is dopamine acting through", "dopamine acting through the", "acting through the d2 subclass", "through the d2 subclass of", "the d2 subclass of dopamine", "d2 subclass of dopamine receptors", "subclass of dopamine receptors present", "of dopamine receptors present in", "dopamine receptors present in lactotrophs", "present in lactotrophs freeman", "in lactotrophs freeman et", "lactotrophs freeman et al.", "freeman et al. 2000 .", "et al. 2000 . prl", "al. 2000 . prl binding", "2000 . prl binding sites", ". prl binding sites or", "prl binding sites or receptors", "binding sites or receptors have", "sites or receptors have been", "or receptors have been identified", "receptors have been identified in", "have been identified in numerous", "been identified in numerous cells", "identified in numerous cells and", "in numerous cells and tissues", "numerous cells and tissues of", "cells and tissues of adult", "and tissues of adult mammals.", "tissues of adult mammals. various", "of adult mammals. various forms", "adult mammals. various forms of", "mammals. various forms of prlr", "forms of prlr generated", "of prlr generated by", "prlr generated by alternative", "by alternative splicing have", "alternative splicing have been", "splicing have been reported", "have been reported in several", "been reported in several species", "reported in several species including", "in several species including humans", "species including humans kelly", "including humans kelly et", "humans kelly et al.", "et al. 1991 clevenger", "al. 1991 clevenger et", "1991 clevenger et al.", "clevenger et al. 2003 .

prlr", "et al. 2003 .

prlr is", "al. 2003 .

prlr is a", "2003 .

prlr is a member", ".

prlr is a member of", "is a member of the", "a member of the cytokine", "member of the cytokine receptor", "of the cytokine receptor superfamily.", "the cytokine receptor superfamily. like", "cytokine receptor superfamily. like many", "receptor superfamily. like many other", "superfamily. like many other members", "like many other members of", "many other members of this", "other members of this family", "of this family the", "this family the first", "family the first step", "the first step in receptor", "first step in receptor activation", "step in receptor activation was", "in receptor activation was generally", "receptor activation was generally believed", "activation was generally believed to", "was generally believed to be", "generally believed to be ligand", "believed to be ligand induced", "to be ligand induced dimerization", "be ligand induced dimerization whereby", "ligand induced dimerization whereby one", "induced dimerization whereby one molecule", "dimerization whereby one molecule of", "whereby one molecule of prl", "one molecule of prl bound", "molecule of prl bound to", "of prl bound to two", "prl bound to two molecules", "bound to two molecules of", "to two molecules of receptor", "molecules of receptor elkins", "of receptor elkins et", "receptor elkins et al.", "elkins et al. 2000 .", "et al. 2000 . recent", "al. 2000 . recent reports", "2000 . recent reports suggest", ". recent reports suggest that", "recent reports suggest that prlr", "reports suggest that prlr pre", "suggest that prlr pre assembles", "that prlr pre assembles at", "prlr pre assembles at the", "pre assembles at the plasma", "assembles at the plasma membrane", "at the plasma membrane in", "the plasma membrane in the", "plasma membrane in the absence", "membrane in the absence of", "in the absence of ligand", "absence of ligand gadd", "of ligand gadd &", "ligand gadd & clevenger", "& clevenger 2006 tallet", "clevenger 2006 tallet et", "2006 tallet et al.", "al. 2011 suggesting", "2011 suggesting that", "suggesting that ligand induced activation", "that ligand induced activation involves", "ligand induced activation involves conformational", "induced activation involves conformational changes", "activation involves conformational changes in", "involves conformational changes in preformed", "conformational changes in preformed prlr", "changes in preformed prlr dimers", "preformed prlr dimers broutin", "prlr dimers broutin et", "dimers broutin et al.", "broutin et al. 2010 .", "et al. 2010 .

prlr", "al. 2010 .

prlr has", "2010 .

prlr has no", ".

prlr has no intrinsic", "

prlr has no intrinsic kinase", "has no intrinsic kinase activity", "no intrinsic kinase activity but", "intrinsic kinase activity but associates", "activity but associates lebrun", "but associates lebrun et", "associates lebrun et al.", "et al. 1994 1995", "1994 1995 with", "1995 with janus kinase", "janus kinase 2 jak2", "2 jak2 which", "jak2 which is activated", "which is activated following receptor", "is activated following receptor activation", "following receptor activation campbell", "receptor activation campbell et", "activation campbell et al.", "et al. 1994 rui", "al. 1994 rui et", "1994 rui et al.", "et al. 1994 carter", "al. 1994 carter su", "1994 carter su et", "carter su et al. 2000", "et al. 2000 barua", "al. 2000 barua et", "2000 barua et al.", "barua et al. 2009 .", "et al. 2009 . jak2", "al. 2009 . jak2 dependent", "2009 . jak2 dependent activation", ". jak2 dependent activation of", "jak2 dependent activation of jak1", "dependent activation of jak1 has", "activation of jak1 has also", "of jak1 has also been", "jak1 has also been reported", "also been reported neilson", "been reported neilson et", "reported neilson et al.", "neilson et al. 2007 .", "et al. 2007 . it", "al. 2007 . it is", "2007 . it is generally", ". it is generally accepted", "it is generally accepted that", "is generally accepted that activation", "generally accepted that activation of", "accepted that activation of jak2", "that activation of jak2 occurs", "activation of jak2 occurs by", "of jak2 occurs by transphosphorylation", "jak2 occurs by transphosphorylation upon", "occurs by transphosphorylation upon ligand", "by transphosphorylation upon ligand induced", "transphosphorylation upon ligand induced receptor", "upon ligand induced receptor activation", "induced receptor activation based", "receptor activation based on", "activation based on jak", "based on jak activation by", "on jak activation by chimeric", "jak activation by chimeric receptors", "activation by chimeric receptors in", "by chimeric receptors in which", "chimeric receptors in which various", "receptors in which various extracellular", "in which various extracellular domains", "which various extracellular domains of", "various extracellular domains of cytokine", "extracellular domains of cytokine or", "domains of cytokine or tyrosine", "of cytokine or tyrosine kinase", "cytokine or tyrosine kinase receptors", "or tyrosine kinase receptors were", "tyrosine kinase receptors were fused", "kinase receptors were fused to", "receptors were fused to the", "were fused to the il", "fused to the il 2", "to the il 2 receptor", "the il 2 receptor beta", "il 2 receptor beta chain", "receptor beta chain see", "beta chain see ihle", "chain see ihle et", "see ihle et al. 1994", "ihle et al. 1994 .", "et al. 1994 . this", "al. 1994 . this activation", "1994 . this activation step", ". this activation step involves", "this activation step involves the", "activation step involves the tyrosine", "step involves the tyrosine phosphorylation", "involves the tyrosine phosphorylation of", "the tyrosine phosphorylation of jak2", "phosphorylation of jak2 which", "of jak2 which in", "jak2 which in turn", "which in turn phosphorylates prlr", "in turn phosphorylates prlr on", "turn phosphorylates prlr on specific", "phosphorylates prlr on specific intracellular", "prlr on specific intracellular tyrosine", "on specific intracellular tyrosine residues", "specific intracellular tyrosine residues leading", "intracellular tyrosine residues leading to", "tyrosine residues leading to stat5", "residues leading to stat5 recruitment", "leading to stat5 recruitment and", "to stat5 recruitment and signaling", "recruitment and signaling considered", "and signaling considered to", "signaling considered to be", "considered to be the most", "to be the most important", "be the most important signaling", "the most important signaling cascade", "most important signaling cascade for", "important signaling cascade for prlr.", "signaling cascade for prlr. stat1", "cascade for prlr. stat1 and", "for prlr. stat1 and stat3", "prlr. stat1 and stat3 activation", "stat1 and stat3 activation have", "and stat3 activation have also", "stat3 activation have also been", "activation have also been reported", "also been reported dasilva", "been reported dasilva et", "reported dasilva et al.", "et al. 1996 as", "al. 1996 as have", "1996 as have many", "as have many other signaling", "have many other signaling pathways", "other signaling pathways signaling", "signaling pathways signaling through", "pathways signaling through map", "through map kinases shc/sos/grb2/ras/raf/mapk", "kinases shc/sos/grb2/ras/raf/mapk has", "shc/sos/grb2/ras/raf/mapk has been reported", "has been reported as a", "been reported as a consequence", "reported as a consequence of", "as a consequence of prl", "a consequence of prl stimuilation", "consequence of prl stimuilation in", "of prl stimuilation in many", "prl stimuilation in many different", "stimuilation in many different cellular", "in many different cellular systems", "different cellular systems see", "cellular systems see bole", "systems see bole feysot", "see bole feysot et al.", "et al. 1998 though", "al. 1998 though it", "1998 though it is", "though it is not clear", "it is not clear how", "is not clear how this", "not clear how this signal", "clear how this signal is", "how this signal is propagated.", "this signal is propagated. other", "signal is propagated. other cascades", "is propagated. other cascades non", "propagated. other cascades non exhaustively", "other cascades non exhaustively include", "cascades non exhaustively include src", "non exhaustively include src kinases", "include src kinases focal", "src kinases focal adhesion", "kinases focal adhesion kinase", "focal adhesion kinase phospholipase", "adhesion kinase phospholipase c", "kinase phospholipase c gamma", "phospholipase c gamma pi3", "c gamma pi3 kinase/akt", "gamma pi3 kinase/akt and", "kinase/akt and nek3 clevenger", "and nek3 clevenger et", "nek3 clevenger et al.", "et al. 2003 miller", "al. 2003 miller et", "2003 miller et al.", "miller et al. 2007 .", "et al. 2007 . the", "al. 2007 . the protein", "2007 . the protein tyrosine", ". the protein tyrosine phosphatase", "the protein tyrosine phosphatase shp2", "protein tyrosine phosphatase shp2 is", "tyrosine phosphatase shp2 is recruited", "phosphatase shp2 is recruited to", "shp2 is recruited to the", "is recruited to the c", "recruited to the c terminal", "to the c terminal tyrosine", "the c terminal tyrosine of", "c terminal tyrosine of prlr", "terminal tyrosine of prlr and", "tyrosine of prlr and may", "of prlr and may have", "prlr and may have a", "and may have a regulatory", "may have a regulatory role", "a regulatory role ali", "regulatory role ali &", "role ali & ali", "ali & ali 2000 .", "& ali 2000 . prlr", "ali 2000 . prlr phosphotyrosines", "2000 . prlr phosphotyrosines can", ". prlr phosphotyrosines can recruit", "prlr phosphotyrosines can recruit insulin", "phosphotyrosines can recruit insulin receptor", "can recruit insulin receptor substrates", "insulin receptor substrates irs", "substrates irs and", "irs and other adaptor", "and other adaptor proteins to", "other adaptor proteins to the", "adaptor proteins to the receptor", "proteins to the receptor complex", "the receptor complex bole", "receptor complex bole feysot", "complex bole feysot et", "feysot et al. 1998 .

female", "et al. 1998 .

female homozygous", "al. 1998 .

female homozygous prlr", "1998 .

female homozygous prlr knockout", ".

female homozygous prlr knockout mice", "homozygous prlr knockout mice are", "prlr knockout mice are completely", "knockout mice are completely infertile", "mice are completely infertile and", "are completely infertile and show", "completely infertile and show a", "infertile and show a lack", "and show a lack of", "show a lack of mammary", "a lack of mammary development", "of mammary development ormandy", "mammary development ormandy et", "development ormandy et al.", "ormandy et al. 1997 .", "et al. 1997 . hemizogotes", "al. 1997 . hemizogotes are", "1997 . hemizogotes are unable", ". hemizogotes are unable to", "hemizogotes are unable to lactate", "are unable to lactate following", "unable to lactate following their", "to lactate following their first", "lactate following their first pregnancy", "following their first pregnancy and", "their first pregnancy and depending", "first pregnancy and depending on", "pregnancy and depending on the", "and depending on the genetic", "depending on the genetic background", "the genetic background this", "genetic background this phenotype", "background this phenotype can", "this phenotype can persist through", "phenotype can persist through subsequent", "can persist through subsequent pregnancies", "through subsequent pregnancies kelly", "subsequent pregnancies kelly et", "pregnancies kelly et al.", "kelly et al. 2001 ." ] }, { "record_id": "GLY_000594_1_744", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1234158", "r hsa", "hsa 1234158", "r hsa 1234158" ] }, { "record_id": "GLY_000594_1_744", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of gene", "gene expression", "expression by", "by hypoxia", "hypoxia inducible", "inducible factor", "regulation of gene", "of gene expression", "gene expression by", "expression by hypoxia", "by hypoxia inducible", "hypoxia inducible factor", "regulation of gene expression", "of 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two pathways: importin", "by two pathways: importin 4/7", "pathways: importin 4/7 chachami", "importin 4/7 chachami et", "4/7 chachami et al.", "et al. 2009 and", "al. 2009 and importin", "2009 and importin alpha/beta", "and importin alpha/beta depping", "importin alpha/beta depping et", "alpha/beta depping et al.", "depping et al. 2008 .", "et al. 2008 . once", "al. 2008 . once in", "2008 . once in the", ". once in the nucleus", "once in the nucleus hif", "in the nucleus hif alpha", "the nucleus hif alpha heterodimerizes", "nucleus hif alpha heterodimerizes with", "hif alpha heterodimerizes with hif", "alpha heterodimerizes with hif beta", "with hif beta arnt", "arnt wang et", "et al. 1995 jiang", "al. 1995 jiang et", "1995 jiang et al.", "et al. 1996 tian", "al. 1996 tian et", "1996 tian et al.", "et al. 1997 gu", "al. 1997 gu et", "1997 gu et al.", "et al. 1998 erbel", "al. 1998 erbel et", "1998 erbel et al.", "et al. 2003 and", "al. 2003 and recruits", "2003 and recruits cbp", "and recruits cbp and p300", "recruits cbp and p300 to", "cbp and p300 to promoters", "and p300 to promoters of", "p300 to promoters of target", "to promoters of target genes", "of target genes ebert", "target genes ebert and", "genes ebert and bunn", "and bunn 1998 kallio", "bunn 1998 kallio et", "1998 kallio et al.", "et al. 1998 ema", "al. 1998 ema et", "1998 ema et al.", "et al. 1999 gu", "al. 1999 gu et", "1999 gu et al.", "et al. 2001 dames", "al. 2001 dames et", "2001 dames et al.", "et al. 2002 freedman", "al. 2002 freedman et", "2002 freedman et al.", "freedman et al. 2002 ." ] }, { "record_id": "GLY_000594_1_745", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1236382", "r hsa", "hsa 1236382", "r hsa 1236382" ] }, { "record_id": "GLY_000594_1_745", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "constitutive signaling", "signaling by", "by ligand", "ligand responsive", "responsive egfr", "egfr cancer", "cancer variants", "constitutive signaling by", "signaling by ligand", "by ligand responsive", "ligand responsive egfr", "responsive egfr cancer", "egfr cancer variants", "constitutive signaling by ligand", "signaling by ligand responsive", "by ligand responsive egfr", "ligand responsive egfr cancer", "responsive egfr cancer variants", "constitutive signaling by ligand responsive", "signaling by ligand responsive egfr", "by ligand responsive egfr cancer", "ligand responsive egfr cancer variants", "by egfr", "egfr is", "is frequently", "frequently activated", "activated in", "in cancer", "cancer through", "through activating", "activating mutations", "mutations in", "in the", "the coding", "coding sequence", "sequence of", "of the", "the egfr", "egfr gene", "resulting in", "in expression", "expression of", "of a", "a constitutively", "constitutively active", "active mutant", "mutant protein.", "protein.

epidermal", "

epidermal growth", "growth factor", "factor receptor", "receptor kinase", "kinase domain", "domain mutants", "mutants are", "are present", "present in", "in ~16%", "~16% of", "of non", "non small", "small cell", "cell lung", "lung cancers", "but are", "are also", "also found", "found in", "in other", "other cancer", "cancer types", "such as", "as breast", "breast cancer", "colorectal cancer", "ovarian cancer", "cancer and", "and thyroid", "thyroid cancer.", "cancer. egfr", "egfr kinase", "mutants harbor", "harbor activating", "in exons", "exons 18", "18 21", "21 which", "which code", "code for", "for the", "the kinase", "amino acids", "acids 712", "712 979", ". small", "small deletions", "insertions or", "or substitutions", "substitutions of", "of amino", "acids within", "within the", "domain lock", "lock egfr", "egfr in", "in its", "its active", "active conformation", "conformation in", "in which", "which the", "the enzyme", "enzyme can", "can dimerize", "dimerize and", "and undergo", "undergo autophosphorylation", "autophosphorylation spontaneously", "without ligand", "ligand binding", "although ligand", "binding ability", "ability is", "is preserved", "and activate", "activate downstream", "downstream signaling", "signaling pathways", "pathways that", "that promote", "promote cell", "cell survival", "greulich et", "et al.", "al. 2005", "zhang et", "al. 2006", "yun et", "al. 2007", "red brewer", "brewer et", "al. 2009", "2009 .", ".

point", "

point mutations", "the extracellular", "extracellular domain", "domain of", "of egfr", "egfr are", "are frequently", "frequently found", "in glioblastoma.", "glioblastoma. similar", "similar to", "to kinase", "domain mutations", "point mutations", "domain result", "result in", "in constitutively", "active egfr", "egfr proteins", "proteins that", "that signal", "signal in", "the absence", "absence of", "of ligands", "but ligand", "ability and", "and responsiveness", "responsiveness are", "are preserved", "lee et", "2006 .", "

egfr kinase", "mutants need", "need to", "to maintain", "maintain association", "association with", "with the", "the chaperone", "chaperone heat", "heat shock", "shock protein", "protein 90", "for proper", "proper functioning", "shimamura et", "lavictoire et", "al. 2003", "2003 .", ". cdc37", "cdc37 is", "is a", "a co", "co chaperone", "chaperone of", "of hsp90", "hsp90 that", "that acts", "acts as", "as a", "a scaffold", "scaffold and", "and regulator", "regulator of", "of interaction", "interaction between", "between hsp90", "hsp90 and", "and its", "its protein", "protein kinase", "kinase clients.", "clients. cdc37", "frequently over", "over expressed", "expressed in", "in cancers", "cancers involving", "involving mutant", "mutant kinases", "kinases and", "and acts", "as an", "an oncogene", "roe et", "al. 2004", "reviewed by", "by gray", "gray jr.", "jr. et", "al. 2008", "2008 .", ".

over", "

over expression", "the wild", "wild type", "type egfr", "egfr or", "or egfr", "cancer mutants", "mutants results", "results in", "in aberrant", "aberrant activation", "activation of", "of downstream", "signaling cascades", "namely ras/raf/map", "ras/raf/map kinase", "kinase signaling", "signaling and", "and pi3k/akt", "pi3k/akt signaling", "and possibly", "possibly signaling", "by plcg1", "which leads", "leads to", "to increased", "increased cell", "cell proliferation", "proliferation and", "and survival", "providing selective", "selective advantage", "advantage to", "to cancer", "cancer cells", "cells that", "that harbor", "sordella et", "huang et", "2007 .", ".

while", "

while growth", "factor activated", "activated wild", "is promptly", "promptly down", "down regulated", "regulated by", "by internalization", "internalization and", "and degradation", "mutants of", "egfr demonstrate", "demonstrate prolonged", "prolonged activation", "lynch et", "2004 .", ". association", "association of", "hsp90 with", "with egfr", "mutants negatively", "negatively affects", "affects cbl", "cbl mediated", "mediated ubiquitination", "possibly through", "through decreasing", "decreasing the", "the affinity", "affinity of", "mutants for", "for phosphorylated", "phosphorylated cbl", "so that", "that cbl", "cbl dissociates", "dissociates from", "from the", "the complex", "complex upon", "upon phosphorylation", "phosphorylation and", "and cannot", "cannot perform", "perform ubiquitination", "yang et", "padron et", "

various molecular", "molecular therapeutics", "therapeutics are", "are being", "being developed", "developed to", "to target", "target aberrantly", "aberrantly activated", "activated egfr", "in cancer.", "cancer. non", "non covalent", "small tyrosine", "tyrosine kinase", "kinase inhibitors", "as gefitinib", "gefitinib and", "and erlotinib", "selectively bind", "bind kinase", "competitively inhibiting", "inhibiting atp", "atp binding", "binding and", "and subsequent", "subsequent autophosphorylation", "autophosphorylation of", "egfr dimers.", "dimers. egfr", "mutants sensitive", "sensitive to", "to non", "covalent tkis", "tkis exhibit", "exhibit greater", "greater affinity", "affinity for", "for tkis", "tkis than", "than atp", "atp compared", "compared with", "egfr protein", "and are", "are therefore", "therefore preferential", "preferential targets", "targets of", "covalent tki", "tki therapeutics", ". egfr", "harbor point", "domain also", "also show", "show sensitivity", "sensitivity to", "covalent tyrosine", "mutants harboring", "harboring small", "small insertions", "insertions in", "in exon", "exon 20", "20 or", "or a", "a secondary", "secondary t790m", "t790m mutation", "mutation are", "are resistant", "resistant to", "to reversible", "reversible tkis", "balak et", "due to", "increased affinity", "for atp", "are targets", "of covalent", "tkis that", "that form", "form a", "a covalent", "covalent bond", "bond with", "egfr cysteine", "cysteine residue", "residue c397.", "c397. however", "effective concentrations", "concentrations of", "tkis also", "also inhibit", "inhibit wild", "causing severe", "severe side", "side effects", "zhou et", ". hence", "tkis have", "have not", "not shown", "shown much", "much promise", "promise in", "in clinical", "clinical trials", "by pao", "pao and", "and chmielecki", "chmielecki in", "in 2010", "2010 .", "signaling by egfr", "by egfr is", "egfr is frequently", "is frequently activated", "frequently activated in", "activated in cancer", "in cancer through", "cancer through activating", "through activating mutations", "activating mutations in", "mutations in the", "in the coding", "the coding sequence", "coding sequence of", "sequence of the", "of the egfr", "the egfr gene", "gene resulting", "resulting in expression", "in expression of", "expression of a", "of a constitutively", "a constitutively active", "constitutively active mutant", "active mutant protein.", "mutant protein.

epidermal", "protein.

epidermal growth", "

epidermal growth factor", "growth factor receptor", "factor receptor kinase", "receptor kinase domain", "kinase domain mutants", "domain mutants are", "mutants are present", "are present in", "present in ~16%", "in ~16% of", "~16% of non", "of non small", "non small cell", "small cell lung", "cell lung cancers", "cancers nsclcs", "but are also", "are also found", "also found in", "found in other", "in other cancer", "other cancer types", "types such", "such as breast", "as breast cancer", "cancer colorectal", "cancer ovarian", "ovarian cancer and", "cancer and thyroid", "and thyroid cancer.", "thyroid cancer. egfr", "cancer. egfr kinase", "egfr kinase domain", "domain mutants harbor", "mutants harbor activating", "harbor activating mutations", "mutations in exons", "in exons 18", "exons 18 21", "18 21 which", "21 which code", "which code for", "code for the", "for the kinase", "the kinase domain", "domain amino", "amino acids 712", "acids 712 979", "979 .", ". small deletions", "deletions insertions", "insertions or substitutions", "or substitutions of", "substitutions of amino", "of amino acids", "amino acids within", "acids within the", "within the kinase", "kinase domain lock", "domain lock egfr", "lock egfr in", "egfr in its", "in its active", "its active conformation", "active conformation in", "conformation in which", "in which the", "which the enzyme", "the enzyme can", "enzyme can dimerize", "can dimerize and", "dimerize and undergo", "and undergo autophosphorylation", "undergo autophosphorylation spontaneously", "spontaneously without", "without ligand binding", "binding although", "although ligand binding", "ligand binding ability", "binding ability is", "ability is preserved", "and activate downstream", "activate downstream signaling", "downstream signaling pathways", "signaling pathways that", "pathways that promote", "that promote cell", "promote cell survival", "survival greulich", "greulich et al.", "et al. 2005", "2005 zhang", "zhang et al.", "et al. 2006", "2006 yun", "yun et al.", "et al. 2007", "2007 red", "red brewer et", "brewer et al.", "et al. 2009", "al. 2009 .", "2009 .

point", ".

point mutations", "

point mutations in", "in the extracellular", "the extracellular domain", "extracellular domain of", "domain of egfr", "of egfr are", "egfr are frequently", "are frequently found", "frequently found in", "found in glioblastoma.", "in glioblastoma. similar", "glioblastoma. similar to", "similar to kinase", "to kinase domain", "kinase domain mutations", "mutations point", "point mutations in", "extracellular domain result", "domain result in", "result in constitutively", "in constitutively active", "constitutively active egfr", "active egfr proteins", "egfr proteins that", "proteins that signal", "that signal in", "signal in the", "in the absence", "the absence of", "absence of ligands", "ligands but", "but ligand binding", "binding ability and", "ability and responsiveness", "and responsiveness are", "responsiveness are preserved", "preserved lee", "lee et al.", "al. 2006 .", ".

egfr", "

egfr kinase domain", "domain mutants need", "mutants need to", "need to maintain", "to maintain association", "maintain association with", "association with the", "with the chaperone", "the chaperone heat", "chaperone heat shock", "heat shock protein", "shock protein 90", "90 hsp90", "hsp90 for", "for proper functioning", "functioning shimamura", "shimamura et al.", "2005 lavictoire", "lavictoire et al.", "et al. 2003", "al. 2003 .", "2003 . cdc37", ". cdc37 is", "cdc37 is a", "is a co", "a co chaperone", "co chaperone of", "chaperone of hsp90", "of hsp90 that", "hsp90 that acts", "that acts as", "acts as a", "as a scaffold", "a scaffold and", "scaffold and regulator", "and regulator of", "regulator of interaction", "of interaction between", "interaction between hsp90", "between hsp90 and", "hsp90 and its", "and its protein", "its protein kinase", "protein kinase clients.", "kinase clients. cdc37", "clients. cdc37 is", "cdc37 is frequently", "is frequently over", "frequently over expressed", "over expressed in", "expressed in cancers", "in cancers involving", "cancers involving mutant", "involving mutant kinases", "mutant kinases and", "kinases and acts", "and acts as", "acts as an", "as an oncogene", "oncogene roe", "roe et al.", "et al. 2004", "2004 reviewed", "reviewed by gray", "by gray jr.", "gray jr. et", "jr. et al.", "et al. 2008", "al. 2008 .", "2008 .

over", ".

over expression", "

over expression of", "expression of the", "of the wild", "the wild type", "wild type egfr", "type egfr or", "egfr or egfr", "or egfr cancer", "egfr cancer mutants", "cancer mutants results", "mutants results in", "results in aberrant", "in aberrant activation", "aberrant activation of", "activation of downstream", "of downstream signaling", "downstream signaling cascades", "cascades namely", "namely ras/raf/map kinase", "ras/raf/map kinase signaling", "kinase signaling and", "signaling and pi3k/akt", "and pi3k/akt signaling", "and possibly signaling", "possibly signaling by", "signaling by plcg1", "plcg1 which", "which leads to", "leads to increased", "to increased cell", "increased cell proliferation", "cell proliferation and", "proliferation and survival", "survival providing", "providing selective advantage", "selective advantage to", "advantage to cancer", "to cancer cells", "cancer cells that", "cells that harbor", "that harbor activating", "in the egfr", "gene sordella", "sordella et al.", "2004 huang", "huang et al.", "al. 2007 .", "2007 .

while", ".

while growth", "

while growth factor", "growth factor activated", "factor activated wild", "activated wild type", "type egfr is", "egfr is promptly", "is promptly down", "promptly down regulated", "down regulated by", "regulated by internalization", "by internalization and", "internalization and degradation", "degradation cancer", "cancer mutants of", "mutants of egfr", "of egfr demonstrate", "egfr demonstrate prolonged", "demonstrate prolonged activation", "activation lynch", "lynch et al.", "al. 2004 .", "2004 . association", ". association of", "association of hsp90", "of hsp90 with", "hsp90 with egfr", "with egfr kinase", "domain mutants negatively", "mutants negatively affects", "negatively affects cbl", "affects cbl mediated", "cbl mediated ubiquitination", "ubiquitination possibly", "possibly through decreasing", "through decreasing the", "decreasing the affinity", "the affinity of", "affinity of egfr", "of egfr kinase", "domain mutants for", "mutants for phosphorylated", "for phosphorylated cbl", "cbl so", "so that cbl", "that cbl dissociates", "cbl dissociates from", "dissociates from the", "from the complex", "the complex upon", "complex upon phosphorylation", "upon phosphorylation and", "phosphorylation and cannot", "and cannot perform", "cannot perform ubiquitination", "ubiquitination yang", "yang et al.", "2006 padron", "padron et al.", ".

various", "

various molecular therapeutics", "molecular therapeutics are", "therapeutics are being", "are being developed", "being developed to", "developed to target", "to target aberrantly", "target aberrantly activated", "aberrantly activated egfr", "activated egfr in", "egfr in cancer.", "in cancer. non", "cancer. non covalent", "covalent reversible", "reversible small", "small tyrosine kinase", "tyrosine kinase inhibitors", "inhibitors tkis", "such as gefitinib", "as gefitinib and", "gefitinib and erlotinib", "erlotinib selectively", "selectively bind kinase", "bind kinase domain", "kinase domain of", "egfr competitively", "competitively inhibiting atp", "inhibiting atp binding", "atp binding and", "binding and subsequent", "and subsequent autophosphorylation", "subsequent autophosphorylation of", "autophosphorylation of egfr", "of egfr dimers.", "egfr dimers. egfr", "dimers. egfr kinase", "domain mutants sensitive", "mutants sensitive to", "sensitive to non", "to non covalent", "non covalent tkis", "covalent tkis exhibit", "tkis exhibit greater", "exhibit greater affinity", "greater affinity for", "affinity for tkis", "for tkis than", "tkis than atp", "than atp compared", "atp compared with", "compared with the", "with the wild", "type egfr protein", "protein and", "and are therefore", "are therefore preferential", "therefore preferential targets", "preferential targets of", "targets of non", "of non covalent", "non covalent tki", "covalent tki therapeutics", "therapeutics yun", "2007 . egfr", ". egfr proteins", "proteins that harbor", "that harbor point", "harbor point mutations", "extracellular domain also", "domain also show", "also show sensitivity", "show sensitivity to", "sensitivity to non", "non covalent tyrosine", "covalent tyrosine kinase", "inhibitors lee", "2006 . egfr", ". egfr kinase", "domain mutants harboring", "mutants harboring small", "harboring small insertions", "small insertions in", "insertions in exon", "in exon 20", "exon 20 or", "20 or a", "or a secondary", "a secondary t790m", "secondary t790m mutation", "t790m mutation are", "mutation are resistant", "are resistant to", "resistant to reversible", "to reversible tkis", "tkis balak", "balak et al.", "2006 due", "due to increased", "to increased affinity", "increased affinity for", "affinity for atp", "atp yun", "and are targets", "are targets of", "targets of covalent", "covalent irreversible", "irreversible tkis", "tkis that form", "that form a", "form a covalent", "a covalent bond", "covalent bond with", "bond with egfr", "with egfr cysteine", "egfr cysteine residue", "cysteine residue c397.", "residue c397. however", "however effective", "effective concentrations of", "concentrations of covalent", "of covalent tkis", "covalent tkis also", "tkis also inhibit", "also inhibit wild", "inhibit wild type", "egfr causing", "causing severe side", "severe side effects", "effects zhou", "zhou et al.", "2009 . hence", "hence covalent", "covalent tkis have", "tkis have not", "have not shown", "not shown much", "shown much promise", "much promise in", "promise in clinical", "in clinical trials", "trials reviewed", "reviewed by pao", "by pao and", "pao and chmielecki", "and chmielecki in", "chmielecki in 2010", "in 2010 .", "signaling by egfr is", "by egfr is frequently", "egfr is frequently activated", "is frequently activated in", "frequently activated in cancer", "activated in cancer through", "in cancer through activating", "cancer through activating mutations", "through activating mutations in", "activating mutations in the", "mutations in the coding", "in the coding sequence", "the coding sequence of", "coding sequence of the", "sequence of the egfr", "of the egfr gene", "egfr gene resulting", "gene resulting in", "resulting in expression of", "in expression of a", "expression of a constitutively", "of a constitutively active", "a constitutively active mutant", "constitutively active mutant protein.", "active mutant protein.

epidermal", "mutant protein.

epidermal growth", "protein.

epidermal growth factor", "

epidermal growth factor receptor", "growth factor receptor kinase", "factor receptor kinase domain", "receptor kinase domain mutants", "kinase domain mutants are", "domain mutants are present", "mutants are present in", "are present in ~16%", "present in ~16% of", "in ~16% of non", "~16% of non small", "of non small cell", "non small cell lung", "small cell lung cancers", "lung cancers nsclcs", "nsclcs but", "but are also found", "are also found in", "also found in other", "found in other cancer", "in other cancer types", "cancer types such", "types such as", "such as breast cancer", "breast cancer colorectal", "cancer colorectal cancer", "colorectal cancer ovarian", "cancer ovarian cancer", "ovarian cancer and thyroid", "cancer and thyroid cancer.", "and thyroid cancer. egfr", "thyroid cancer. egfr kinase", "cancer. egfr kinase domain", "egfr kinase domain mutants", "kinase domain mutants harbor", "domain mutants harbor activating", "mutants harbor activating mutations", "harbor activating mutations in", "activating mutations in exons", "mutations in exons 18", "in exons 18 21", "exons 18 21 which", "18 21 which code", "21 which code for", "which code for the", "code for the kinase", "for the kinase domain", "kinase domain amino", "domain amino acids", "amino acids 712 979", "712 979 .", "979 . small", "small deletions insertions", "deletions insertions or", "insertions or substitutions of", "or substitutions of amino", "substitutions of amino acids", "of amino acids within", "amino acids within the", "acids within the kinase", "within the kinase domain", "the kinase domain lock", "kinase domain lock egfr", "domain lock egfr in", "lock egfr in its", "egfr in its active", "in its active conformation", "its active conformation in", "active conformation in which", "conformation in which the", "in which the enzyme", "which the enzyme can", "the enzyme can dimerize", "enzyme can dimerize and", "can dimerize and undergo", "dimerize and undergo autophosphorylation", "and undergo autophosphorylation spontaneously", "autophosphorylation spontaneously without", "spontaneously without ligand", "ligand binding although", "binding although ligand", "although ligand binding ability", "ligand binding ability is", "binding ability is preserved", "preserved and", "and activate downstream signaling", "activate downstream signaling pathways", "downstream signaling pathways that", "signaling pathways that promote", "pathways that promote cell", "that promote cell survival", "cell survival greulich", "survival greulich et", "greulich et al. 2005", "al. 2005 zhang", "2005 zhang et", "zhang et al. 2006", "al. 2006 yun", "2006 yun et", "yun et al. 2007", "al. 2007 red", "2007 red brewer", "red brewer et al.", "brewer et al. 2009", "et al. 2009 .", "al. 2009 .

point", "2009 .

point mutations", ".

point mutations in", "

point mutations in the", "mutations in the extracellular", "in the extracellular domain", "the extracellular domain of", "extracellular domain of egfr", "domain of egfr are", "of egfr are frequently", "egfr are frequently found", "are frequently found in", "frequently found in glioblastoma.", "found in glioblastoma. similar", "in glioblastoma. similar to", "glioblastoma. similar to kinase", "similar to kinase domain", "to kinase domain mutations", "domain mutations point", "mutations point mutations", "point mutations in the", "the extracellular domain result", "extracellular domain result in", "domain result in constitutively", "result in constitutively active", "in constitutively active egfr", "constitutively active egfr proteins", "active egfr proteins that", "egfr proteins that signal", "proteins that signal in", "that signal in the", "signal in the absence", "in the absence of", "the absence of ligands", "of ligands but", "ligands but ligand", "but ligand binding ability", "ligand binding ability and", "binding ability and responsiveness", "ability and responsiveness are", "and responsiveness are preserved", "are preserved lee", "preserved lee et", "lee et al. 2006", "et al. 2006 .", "2006 .

egfr", ".

egfr kinase", "

egfr kinase domain mutants", "kinase domain mutants need", "domain mutants need to", "mutants need to maintain", "need to maintain association", "to maintain association with", "maintain association with the", "association with the chaperone", "with the chaperone heat", "the chaperone heat shock", "chaperone heat shock protein", "heat shock protein 90", "protein 90 hsp90", "hsp90 for proper", "proper functioning shimamura", "functioning shimamura et", "shimamura et al. 2005", "al. 2005 lavictoire", "2005 lavictoire et", "lavictoire et al. 2003", "et al. 2003 .", "al. 2003 . cdc37", "2003 . cdc37 is", ". cdc37 is a", "cdc37 is a co", "is a co chaperone", "a co chaperone of", "co chaperone of hsp90", "chaperone of hsp90 that", "of hsp90 that acts", "hsp90 that acts as", "that acts as a", "acts as a scaffold", "as a scaffold and", "a scaffold and regulator", "scaffold and regulator of", "and regulator of interaction", "regulator of interaction between", "of interaction between hsp90", "interaction between hsp90 and", "between hsp90 and its", "hsp90 and its protein", "and its protein kinase", "its protein kinase clients.", "protein kinase clients. cdc37", "kinase clients. cdc37 is", "clients. cdc37 is frequently", "cdc37 is frequently over", "is frequently over expressed", "frequently over expressed in", "over expressed in cancers", "expressed in cancers involving", "in cancers involving mutant", "cancers involving mutant kinases", "involving mutant kinases and", "mutant kinases and acts", "kinases and acts as", "and acts as an", "acts as an oncogene", "an oncogene roe", "oncogene roe et", "roe et al. 2004", "al. 2004 reviewed", "2004 reviewed by", "reviewed by gray jr.", "by gray jr. et", "gray jr. et al.", "jr. et al. 2008", "et al. 2008 .", "al. 2008 .

over", "2008 .

over expression", ".

over expression of", "

over expression of the", "expression of the wild", "of the wild type", "the wild type egfr", "wild type egfr or", "type egfr or egfr", "egfr or egfr cancer", "or egfr cancer mutants", "egfr cancer mutants results", "cancer mutants results in", "mutants results in aberrant", "results in aberrant activation", "in aberrant activation of", "aberrant activation of downstream", "activation of downstream signaling", "of downstream signaling cascades", "signaling cascades namely", "cascades namely ras/raf/map", "namely ras/raf/map kinase signaling", "ras/raf/map kinase signaling and", "kinase signaling and pi3k/akt", "signaling and pi3k/akt signaling", "pi3k/akt signaling and", "signaling and possibly", "and possibly signaling by", "possibly signaling by plcg1", "by plcg1 which", "plcg1 which leads", "which leads to increased", "leads to increased cell", "to increased cell proliferation", "increased cell proliferation and", "cell proliferation and survival", "and survival providing", "survival providing selective", "providing selective advantage to", "selective advantage to cancer", "advantage to cancer cells", "to cancer cells that", "cancer cells that harbor", "cells that harbor activating", "that harbor activating mutations", "mutations in the egfr", "in the egfr gene", "egfr gene sordella", "gene sordella et", "sordella et al. 2004", "al. 2004 huang", "2004 huang et", "huang et al. 2007", "et al. 2007 .", "al. 2007 .

while", "2007 .

while growth", ".

while growth factor", "

while growth factor activated", "growth factor activated wild", "factor activated wild type", "activated wild type egfr", "wild type egfr is", "type egfr is promptly", "egfr is promptly down", "is promptly down regulated", "promptly down regulated by", "down regulated by internalization", "regulated by internalization and", "by internalization and degradation", "and degradation cancer", "degradation cancer mutants", "cancer mutants of egfr", "mutants of egfr demonstrate", "of egfr demonstrate prolonged", "egfr demonstrate prolonged activation", "prolonged activation lynch", "activation lynch et", "lynch et al. 2004", "et al. 2004 .", "al. 2004 . association", "2004 . association of", ". association of hsp90", "association of hsp90 with", "of hsp90 with egfr", "hsp90 with egfr kinase", "with egfr kinase domain", "kinase domain mutants negatively", "domain mutants negatively affects", "mutants negatively affects cbl", "negatively affects cbl mediated", "affects cbl mediated ubiquitination", "mediated ubiquitination possibly", "ubiquitination possibly through", "possibly through decreasing the", "through decreasing the affinity", "decreasing the affinity of", "the affinity of egfr", "affinity of egfr kinase", "of egfr kinase domain", "kinase domain mutants for", "domain mutants for phosphorylated", "mutants for phosphorylated cbl", "phosphorylated cbl so", "cbl so that", "so that cbl dissociates", "that cbl dissociates from", "cbl dissociates from the", "dissociates from the complex", "from the complex upon", "the complex upon phosphorylation", "complex upon phosphorylation and", "upon phosphorylation and cannot", "phosphorylation and cannot perform", "and cannot perform ubiquitination", "perform ubiquitination yang", "ubiquitination yang et", "yang et al. 2006", "al. 2006 padron", "2006 padron et", "padron et al. 2007", "2007 .

various", ".

various molecular", "

various molecular therapeutics are", "molecular therapeutics are being", "therapeutics are being developed", "are being developed to", "being developed to target", "developed to target aberrantly", "to target aberrantly activated", "target aberrantly activated egfr", "aberrantly activated egfr in", "activated egfr in cancer.", "egfr in cancer. non", "in cancer. non covalent", "non covalent reversible", "reversible small tyrosine", "small tyrosine kinase inhibitors", "kinase inhibitors tkis", "tkis such", "such as gefitinib and", "as gefitinib and erlotinib", "and erlotinib selectively", "erlotinib selectively bind", "selectively bind kinase domain", "bind kinase domain of", "kinase domain of egfr", "of egfr competitively", "egfr competitively inhibiting", "competitively inhibiting atp binding", "inhibiting atp binding and", "atp binding and subsequent", "binding and subsequent autophosphorylation", "and subsequent autophosphorylation of", "subsequent autophosphorylation of egfr", "autophosphorylation of egfr dimers.", "of egfr dimers. egfr", "egfr dimers. egfr kinase", "dimers. egfr kinase domain", "kinase domain mutants sensitive", "domain mutants sensitive to", "mutants sensitive to non", "sensitive to non covalent", "to non covalent tkis", "non covalent tkis exhibit", "covalent tkis exhibit greater", "tkis exhibit greater affinity", "exhibit greater affinity for", "greater affinity for tkis", "affinity for tkis than", "for tkis than atp", "tkis than atp compared", "than atp compared with", "atp compared with the", "compared with the wild", "with the wild type", "wild type egfr protein", "egfr protein and", "protein and are", "and are therefore preferential", "are therefore preferential targets", "therefore preferential targets of", "preferential targets of non", "targets of non covalent", "of non covalent tki", "non covalent tki therapeutics", "tki therapeutics yun", "therapeutics yun et", "al. 2007 . egfr", "2007 . egfr proteins", ". egfr proteins that", "egfr proteins that harbor", "proteins that harbor point", "that harbor point mutations", "harbor point mutations in", "the extracellular domain also", "extracellular domain also show", "domain also show sensitivity", "also show sensitivity to", "show sensitivity to non", "sensitivity to non covalent", "to non covalent tyrosine", "non covalent tyrosine kinase", "covalent tyrosine kinase inhibitors", "kinase inhibitors lee", "inhibitors lee et", "al. 2006 . egfr", "2006 . egfr kinase", ". egfr kinase domain", "kinase domain mutants harboring", "domain mutants harboring small", "mutants harboring small insertions", "harboring small insertions in", "small insertions in exon", "insertions in exon 20", "in exon 20 or", "exon 20 or a", "20 or a secondary", "or a secondary t790m", "a secondary t790m mutation", "secondary t790m mutation are", "t790m mutation are resistant", "mutation are resistant to", "are resistant to reversible", "resistant to reversible tkis", "reversible tkis balak", "tkis balak et", "balak et al. 2006", "al. 2006 due", "2006 due to", "due to increased affinity", "to increased affinity for", "increased affinity for atp", "for atp yun", "atp yun et", "yun et al. 2008", "2008 and", "and are targets of", "are targets of covalent", "of covalent irreversible", "irreversible tkis that", "tkis that form a", "that form a covalent", "form a covalent bond", "a covalent bond with", "covalent bond with egfr", "bond with egfr cysteine", "with egfr cysteine residue", "egfr cysteine residue c397.", "cysteine residue c397. however", "c397. however effective", "however effective concentrations", "effective concentrations of covalent", "concentrations of covalent tkis", "of covalent tkis also", "covalent tkis also inhibit", "tkis also inhibit wild", "also inhibit wild type", "inhibit wild type egfr", "type egfr causing", "egfr causing severe", "causing severe side effects", "side effects zhou", "effects zhou et", "zhou et al. 2009", "al. 2009 . hence", ". hence covalent", "hence covalent tkis", "covalent tkis have not", "tkis have not shown", "have not shown much", "not shown much promise", "shown much promise in", "much promise in clinical", "promise in clinical trials", "clinical trials reviewed", "trials reviewed by", "reviewed by pao and", "by pao and chmielecki", "pao and chmielecki in", "and chmielecki in 2010", "chmielecki in 2010 .", "signaling by egfr is frequently", "by egfr is frequently activated", "egfr is frequently activated in", "is frequently activated in cancer", "frequently activated in cancer through", "activated in cancer through activating", "in cancer through activating mutations", "cancer through activating mutations in", "through activating mutations in the", "activating mutations in the coding", "mutations in the coding sequence", "in the coding sequence of", "the coding sequence of the", "coding sequence of the egfr", "sequence of the egfr gene", "the egfr gene resulting", "egfr gene resulting in", "gene resulting in expression", "resulting in expression of a", "in expression of a constitutively", "expression of a constitutively active", "of a constitutively active mutant", "a constitutively active mutant protein.", "constitutively active mutant protein.

epidermal", "active mutant protein.

epidermal growth", "mutant protein.

epidermal growth factor", "protein.

epidermal growth factor receptor", "

epidermal growth factor receptor kinase", "growth factor receptor kinase domain", "factor receptor kinase domain mutants", "receptor kinase domain mutants are", "kinase domain mutants are present", "domain mutants are present in", "mutants are present in ~16%", "are present in ~16% of", "present in ~16% of non", "in ~16% of non small", "~16% of non small cell", "of non small cell lung", "non small cell lung cancers", "cell lung cancers nsclcs", "nsclcs but are", "but are also found in", "are also found in other", "also found in other cancer", "found in other cancer types", "other cancer types such", "cancer types such as", "types such as breast", "as breast cancer colorectal", "breast cancer colorectal cancer", "colorectal cancer ovarian cancer", "cancer ovarian cancer and", "ovarian cancer and thyroid cancer.", "cancer and thyroid cancer. egfr", "and thyroid cancer. egfr kinase", "thyroid cancer. egfr kinase domain", "cancer. egfr kinase domain mutants", "egfr kinase domain mutants harbor", "kinase domain mutants harbor activating", "domain mutants harbor activating mutations", "mutants harbor activating mutations in", "harbor activating mutations in exons", "activating mutations in exons 18", "mutations in exons 18 21", "in exons 18 21 which", "exons 18 21 which code", "18 21 which code for", "21 which code for the", "which code for the kinase", "code for the kinase domain", "the kinase domain amino", "kinase domain amino acids", "domain amino acids 712", "acids 712 979 .", "712 979 . small", "979 . small deletions", ". small deletions insertions", "small deletions insertions or", "deletions insertions or substitutions", "insertions or substitutions of amino", "or substitutions of amino acids", "substitutions of amino acids within", "of amino acids within the", "amino acids within the kinase", "acids within the kinase domain", "within the kinase domain lock", "the kinase domain lock egfr", "kinase domain lock egfr in", "domain lock egfr in its", "lock egfr in its active", "egfr in its active conformation", "in its active conformation in", "its active conformation in which", "active conformation in which the", "conformation in which the enzyme", "in which the enzyme can", "which the enzyme can dimerize", "the enzyme can dimerize and", "enzyme can dimerize and undergo", "can dimerize and undergo autophosphorylation", "dimerize and undergo autophosphorylation spontaneously", "undergo autophosphorylation spontaneously without", "autophosphorylation spontaneously without ligand", "spontaneously without ligand binding", "without ligand binding although", "ligand binding although ligand", "binding although ligand binding", "although ligand binding ability is", "ligand binding ability is preserved", "is preserved and", "preserved and activate", "and activate downstream signaling pathways", "activate downstream signaling pathways that", "downstream signaling pathways that promote", "signaling pathways that promote cell", "pathways that promote cell survival", "promote cell survival greulich", "cell survival greulich et", "survival greulich et al.", "et al. 2005 zhang", "al. 2005 zhang et", "2005 zhang et al.", "et al. 2006 yun", "al. 2006 yun et", "2006 yun et al.", "et al. 2007 red", "al. 2007 red brewer", "2007 red brewer et", "red brewer et al. 2009", "brewer et al. 2009 .", "et al. 2009 .

point", "al. 2009 .

point mutations", "2009 .

point mutations in", ".

point mutations in the", "

point mutations in the extracellular", "mutations in the extracellular domain", "in the extracellular domain of", "the extracellular domain of egfr", "extracellular domain of egfr are", "domain of egfr are frequently", "of egfr are frequently found", "egfr are frequently found in", "are frequently found in glioblastoma.", "frequently found in glioblastoma. similar", "found in glioblastoma. similar to", "in glioblastoma. similar to kinase", "glioblastoma. similar to kinase domain", "similar to kinase domain mutations", "kinase domain mutations point", "domain mutations point mutations", "mutations point mutations in", "point mutations in the extracellular", "in the extracellular domain result", "the extracellular domain result in", "extracellular domain result in constitutively", "domain result in constitutively active", "result in constitutively active egfr", "in constitutively active egfr proteins", "constitutively active egfr proteins that", "active egfr proteins that signal", "egfr proteins that signal in", "proteins that signal in the", "that signal in the absence", "signal in the absence of", "in the absence of ligands", "absence of ligands but", "of ligands but ligand", "ligands but ligand binding", "but ligand binding ability and", "ligand binding ability and responsiveness", "binding ability and responsiveness are", "ability and responsiveness are preserved", "responsiveness are preserved lee", "are preserved lee et", "preserved lee et al.", "lee et al. 2006 .", "al. 2006 .

egfr", "2006 .

egfr kinase", ".

egfr kinase domain", "

egfr kinase domain mutants need", "kinase domain mutants need to", "domain mutants need to maintain", "mutants need to maintain association", "need to maintain association with", "to maintain association with the", "maintain association with the chaperone", "association with the chaperone heat", "with the chaperone heat shock", "the chaperone heat shock protein", "chaperone heat shock protein 90", "shock protein 90 hsp90", "90 hsp90 for", "hsp90 for proper functioning", "for proper functioning shimamura", "proper functioning shimamura et", "functioning shimamura et al.", "et al. 2005 lavictoire", "al. 2005 lavictoire et", "2005 lavictoire et al.", "lavictoire et al. 2003 .", "et al. 2003 . cdc37", "al. 2003 . cdc37 is", "2003 . cdc37 is a", ". cdc37 is a co", "cdc37 is a co chaperone", "is a co chaperone of", "a co chaperone of hsp90", "co chaperone of hsp90 that", "chaperone of hsp90 that acts", "of hsp90 that acts as", "hsp90 that acts as a", "that acts as a scaffold", "acts as a scaffold and", "as a scaffold and regulator", "a scaffold and regulator of", "scaffold and regulator of interaction", "and regulator of interaction between", "regulator of interaction between hsp90", "of interaction between hsp90 and", "interaction between hsp90 and its", "between hsp90 and its protein", "hsp90 and its protein kinase", "and its protein kinase clients.", "its protein kinase clients. cdc37", "protein kinase clients. cdc37 is", "kinase clients. cdc37 is frequently", "clients. cdc37 is frequently over", "cdc37 is frequently over expressed", "is frequently over expressed in", "frequently over expressed in cancers", "over expressed in cancers involving", "expressed in cancers involving mutant", "in cancers involving mutant kinases", "cancers involving mutant kinases and", "involving mutant kinases and acts", "mutant kinases and acts as", "kinases and acts as an", "and acts as an oncogene", "as an oncogene roe", "an oncogene roe et", "oncogene roe et al.", "et al. 2004 reviewed", "al. 2004 reviewed by", "2004 reviewed by gray", "reviewed by gray jr. et", "by gray jr. et al.", "gray jr. et al. 2008", "jr. et al. 2008 .", "et al. 2008 .

over", "al. 2008 .

over expression", "2008 .

over expression of", ".

over expression of the", "

over expression of the wild", "expression of the wild type", "of the wild type egfr", "the wild type egfr or", "wild type egfr or egfr", "type egfr or egfr cancer", "egfr or egfr cancer mutants", "or egfr cancer mutants results", "egfr cancer mutants results in", "cancer mutants results in aberrant", "mutants results in aberrant activation", "results in aberrant activation of", "in aberrant activation of downstream", "aberrant activation of downstream signaling", "activation of downstream signaling cascades", "downstream signaling cascades namely", "signaling cascades namely ras/raf/map", "cascades namely ras/raf/map kinase", "namely ras/raf/map kinase signaling and", "ras/raf/map kinase signaling and pi3k/akt", "kinase signaling and pi3k/akt signaling", "and pi3k/akt signaling and", "pi3k/akt signaling and possibly", "signaling and possibly signaling", "and possibly signaling by plcg1", "signaling by plcg1 which", "by plcg1 which leads", "plcg1 which leads to", "which leads to increased cell", "leads to increased cell proliferation", "to increased cell proliferation and", "increased cell proliferation and survival", "proliferation and survival providing", "and survival providing selective", "survival providing selective advantage", "providing selective advantage to cancer", "selective advantage to cancer cells", "advantage to cancer cells that", "to cancer cells that harbor", "cancer cells that harbor activating", "cells that harbor activating mutations", "that harbor activating mutations in", "harbor activating mutations in the", "activating mutations in the egfr", "mutations in the egfr gene", "the egfr gene sordella", "egfr gene sordella et", "gene sordella et al.", "et al. 2004 huang", "al. 2004 huang et", "2004 huang et al.", "huang et al. 2007 .", "et al. 2007 .

while", "al. 2007 .

while growth", "2007 .

while growth factor", ".

while growth factor activated", "

while growth factor activated wild", "growth factor activated wild type", "factor activated wild type egfr", "activated wild type egfr is", "wild type egfr is promptly", "type egfr is promptly down", "egfr is promptly down regulated", "is promptly down regulated by", "promptly down regulated by internalization", "down regulated by internalization and", "regulated by internalization and degradation", "internalization and degradation cancer", "and degradation cancer mutants", "degradation cancer mutants of", "cancer mutants of egfr demonstrate", "mutants of egfr demonstrate prolonged", "of egfr demonstrate prolonged activation", "demonstrate prolonged activation lynch", "prolonged activation lynch et", "activation lynch et al.", "lynch et al. 2004 .", "et al. 2004 . association", "al. 2004 . association of", "2004 . association of hsp90", ". association of hsp90 with", "association of hsp90 with egfr", "of hsp90 with egfr kinase", "hsp90 with egfr kinase domain", "with egfr kinase domain mutants", "egfr kinase domain mutants negatively", "kinase domain mutants negatively affects", "domain mutants negatively affects cbl", "mutants negatively affects cbl mediated", "negatively affects cbl mediated ubiquitination", "cbl mediated ubiquitination possibly", "mediated ubiquitination possibly through", "ubiquitination possibly through decreasing", "possibly through decreasing the affinity", "through decreasing the affinity of", "decreasing the affinity of egfr", "the affinity of egfr kinase", "affinity of egfr kinase domain", "of egfr kinase domain mutants", "egfr kinase domain mutants for", "kinase domain mutants for phosphorylated", "domain mutants for phosphorylated cbl", "for phosphorylated cbl so", "phosphorylated cbl so that", "cbl so that cbl", "so that cbl dissociates from", "that cbl dissociates from the", "cbl dissociates from the complex", "dissociates from the complex upon", "from the complex upon phosphorylation", "the complex upon phosphorylation and", "complex upon phosphorylation and cannot", "upon phosphorylation and cannot perform", "phosphorylation and cannot perform ubiquitination", "cannot perform ubiquitination yang", "perform ubiquitination yang et", "ubiquitination yang et al.", "et al. 2006 padron", "al. 2006 padron et", "2006 padron et al.", "padron et al. 2007 .", "al. 2007 .

various", "2007 .

various molecular", ".

various molecular therapeutics", "

various molecular therapeutics are being", "molecular therapeutics are being developed", "therapeutics are being developed to", "are being developed to target", "being developed to target aberrantly", "developed to target aberrantly activated", "to target aberrantly activated egfr", "target aberrantly activated egfr in", "aberrantly activated egfr in cancer.", "activated egfr in cancer. non", "egfr in cancer. non covalent", "cancer. non covalent reversible", "covalent reversible small", "reversible small tyrosine kinase", "tyrosine kinase inhibitors tkis", "tkis such as", "such as gefitinib and erlotinib", "gefitinib and erlotinib selectively", "and erlotinib selectively bind", "erlotinib selectively bind kinase", "selectively bind kinase domain of", "bind kinase domain of egfr", "domain of egfr competitively", "of egfr competitively inhibiting", "egfr competitively inhibiting atp", "competitively inhibiting atp binding and", "inhibiting atp binding and subsequent", "atp binding and subsequent autophosphorylation", "binding and subsequent autophosphorylation of", "and subsequent autophosphorylation of egfr", "subsequent autophosphorylation of egfr dimers.", "autophosphorylation of egfr dimers. egfr", "of egfr dimers. egfr kinase", "egfr dimers. egfr kinase domain", "dimers. egfr kinase domain mutants", "egfr kinase domain mutants sensitive", "kinase domain mutants sensitive to", "domain mutants sensitive to non", "mutants sensitive to non covalent", "sensitive to non covalent tkis", "to non covalent tkis exhibit", "non covalent tkis exhibit greater", "covalent tkis exhibit greater affinity", "tkis exhibit greater affinity for", "exhibit greater affinity for tkis", "greater affinity for tkis than", "affinity for tkis than atp", "for tkis than atp compared", "tkis than atp compared with", "than atp compared with the", "atp compared with the wild", "compared with the wild type", "with the wild type egfr", "the wild type egfr protein", "type egfr protein and", "egfr protein and are", "protein and are therefore", "and are therefore preferential targets", "are therefore preferential targets of", "therefore preferential targets of non", "preferential targets of non covalent", "targets of non covalent tki", "of non covalent tki therapeutics", "covalent tki therapeutics yun", "tki therapeutics yun et", "therapeutics yun et al.", "yun et al. 2007 .", "et al. 2007 . egfr", "al. 2007 . egfr proteins", "2007 . egfr proteins that", ". egfr proteins that harbor", "egfr proteins that harbor point", "proteins that harbor point mutations", "that harbor point mutations in", "harbor point mutations in the", "in the extracellular domain also", "the extracellular domain also show", "extracellular domain also show sensitivity", "domain also show sensitivity to", "also show sensitivity to non", "show sensitivity to non covalent", "sensitivity to non covalent tyrosine", "to non covalent tyrosine kinase", "non covalent tyrosine kinase inhibitors", "tyrosine kinase inhibitors lee", "kinase inhibitors lee et", "inhibitors lee et al.", "et al. 2006 . egfr", "al. 2006 . egfr kinase", "2006 . egfr kinase domain", ". egfr kinase domain mutants", "egfr kinase domain mutants harboring", "kinase domain mutants harboring small", "domain mutants harboring small insertions", "mutants harboring small insertions in", "harboring small insertions in exon", "small insertions in exon 20", "insertions in exon 20 or", "in exon 20 or a", "exon 20 or a secondary", "20 or a secondary t790m", "or a secondary t790m mutation", "a secondary t790m mutation are", "secondary t790m mutation are resistant", "t790m mutation are resistant to", "mutation are resistant to reversible", "are resistant to reversible tkis", "to reversible tkis balak", "reversible tkis balak et", "tkis balak et al.", "et al. 2006 due", "al. 2006 due to", "2006 due to increased", "due to increased affinity for", "to increased affinity for atp", "affinity for atp yun", "for atp yun et", "atp yun et al.", "al. 2008 and", "2008 and are", "and are targets of covalent", "targets of covalent irreversible", "covalent irreversible tkis", "irreversible tkis that form", "tkis that form a covalent", "that form a covalent bond", "form a covalent bond with", "a covalent bond with egfr", "covalent bond with egfr cysteine", "bond with egfr cysteine residue", "with egfr cysteine residue c397.", "egfr cysteine residue c397. however", "residue c397. however effective", "c397. however effective concentrations", "however effective concentrations of", "effective concentrations of covalent tkis", "concentrations of covalent tkis also", "of covalent tkis also inhibit", "covalent tkis also inhibit wild", "tkis also inhibit wild type", "also inhibit wild type egfr", "wild type egfr causing", "type egfr causing severe", "egfr causing severe side", "severe side effects zhou", "side effects zhou et", "effects zhou et al.", "zhou et al. 2009 .", "et al. 2009 . hence", "2009 . hence covalent", ". hence covalent tkis", "hence covalent tkis have", "covalent tkis have not shown", "tkis have not shown much", "have not shown much promise", "not shown much promise in", "shown much promise in clinical", "much promise in clinical trials", "in clinical trials reviewed", "clinical trials reviewed by", "trials reviewed by pao", "reviewed by pao and chmielecki", "by pao and chmielecki in", "pao and chmielecki in 2010", "and chmielecki in 2010 ." ] }, { "record_id": "GLY_000594_1_746", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1236977", "r hsa", "hsa 1236977", "r hsa 1236977" ] }, { "record_id": "GLY_000594_1_746", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "endosomal/vacuolar pathway", "some antigens", "antigens are", "are cross", "cross presented", "presented through", "through a", "a vacuolar", "vacuolar mechanism", "mechanism that", "that involves", "involves generation", "generation of", "of antigenic", "antigenic peptides", "peptides and", "and their", "their loading", "loading on", "on to", "to mhc", "mhc i", "i molecules", "molecules within", "within the", "the endosomal", "endosomal compartment", "compartment in", "in a", "a proteasome", "proteasome and", "and tap", "tap independent", "independent manner.", "manner. antigens", "antigens within", "the endosome", "endosome are", "are processed", "processed by", "by cathepsin", "cathepsin s", "s and", "and other", "other proteases", "proteases into", "into antigenic", "antigenic peptides.", "peptides. loading", "loading of", "of these", "these peptides", "peptides onto", "onto mhc", "molecules occurs", "occurs directly", "directly within", "within early", "early and", "and late", "late endosomal", "endosomal compartments.", "compartments. why", "why certain", "certain antigens", "presented exclusively", "exclusively by", "by the", "the cytosolic", "cytosolic pathway", "pathway while", "while others", "others use", "use the", "the vacuolar", "vacuolar pathway", "pathway is", "is unknown.", "unknown. it", "it may", "may be", "be because", "because some", "some epitopes", "epitopes cannot", "cannot be", "be generated", "generated by", "by endosomal", "endosomal proteolysis", "or are", "are completely", "completely destroyed.", "destroyed. alternatively", "the physical", "physical form", "form of", "of the", "the antigen", "antigen may", "may influence", "influence its", "its accessibility", "accessibility to", "to the", "endosomal or", "or vacuolar", "vacuolar pathways", "shen et", "et al.", "al. 2004", "2004 .", "some antigens are", "antigens are cross", "are cross presented", "cross presented through", "presented through a", "through a vacuolar", "a vacuolar mechanism", "vacuolar mechanism that", "mechanism that involves", "that involves generation", "involves generation of", "generation of antigenic", "of antigenic peptides", "antigenic peptides and", "peptides and their", "and their loading", "their 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"late endosomal compartments.", "endosomal compartments. why", "compartments. why certain", "why certain antigens", "certain antigens are", "cross presented exclusively", "presented exclusively by", "exclusively by the", "by the cytosolic", "the cytosolic pathway", "cytosolic pathway while", "pathway while others", "while others use", "others use the", "use the vacuolar", "the vacuolar pathway", "vacuolar pathway is", "pathway is unknown.", "is unknown. it", "unknown. it may", "it may be", "may be because", "be because some", "because some epitopes", "some epitopes cannot", "epitopes cannot be", "cannot be generated", "be generated by", "generated by endosomal", "by endosomal proteolysis", "proteolysis or", "or are completely", "are completely destroyed.", "completely destroyed. alternatively", "alternatively the", "the physical form", "physical form of", "form of the", "of the antigen", "the antigen may", "antigen may influence", "may influence its", "influence its accessibility", "its accessibility to", "accessibility to the", "to the endosomal", "the endosomal or", "endosomal or vacuolar", "or vacuolar pathways", "pathways shen", "shen et al.", "et al. 2004", "al. 2004 .", "some antigens are cross", "antigens are cross presented", "are cross presented through", "cross presented through a", "presented through a vacuolar", "through a vacuolar mechanism", "a vacuolar mechanism that", "vacuolar mechanism that involves", "mechanism that involves generation", "that involves generation of", "involves generation of antigenic", "generation of antigenic peptides", "of antigenic peptides and", "antigenic peptides and their", "peptides and their loading", "and their loading on", "their loading on to", "loading on to mhc", "on to mhc i", "to mhc i molecules", "mhc i molecules within", "i molecules within the", "molecules within the endosomal", "within the endosomal compartment", "the endosomal compartment in", "endosomal compartment in a", "compartment in a proteasome", "in a proteasome and", "a proteasome and tap", "proteasome and tap independent", "and tap independent manner.", "tap independent manner. antigens", "independent manner. antigens within", "manner. antigens within the", "antigens within the endosome", "within the endosome are", "the endosome are processed", "endosome are processed by", "are processed by cathepsin", "processed by cathepsin s", "by cathepsin s and", "cathepsin s and other", "s and other proteases", "and other proteases into", "other proteases into antigenic", "proteases into antigenic peptides.", "into antigenic peptides. loading", "antigenic peptides. loading of", "peptides. loading of these", "loading of these peptides", "of these peptides onto", "these peptides onto mhc", "peptides onto mhc i", "onto mhc i molecules", "mhc i molecules occurs", "i molecules occurs directly", "molecules occurs directly within", "occurs directly within early", "directly within early and", "within early and late", "early and late endosomal", "and late endosomal compartments.", "late endosomal compartments. why", "endosomal compartments. why certain", "compartments. why certain antigens", "why certain antigens are", "certain antigens are cross", "are cross presented exclusively", "cross presented exclusively by", "presented exclusively by the", "exclusively by the cytosolic", "by the cytosolic pathway", "the cytosolic pathway while", "cytosolic pathway while others", "pathway while others use", "while others use the", "others use the vacuolar", "use the vacuolar pathway", "the vacuolar pathway is", "vacuolar pathway is unknown.", "pathway is unknown. it", "is unknown. it may", "unknown. it may be", "it may be because", "may be because some", "be because some epitopes", "because some epitopes cannot", "some epitopes cannot be", "epitopes cannot be generated", "cannot be generated by", "be generated by endosomal", "generated by endosomal proteolysis", "endosomal proteolysis or", "proteolysis or are", "or are 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"proteolysis or are completely", "or are completely destroyed. alternatively", "completely destroyed. alternatively the", "destroyed. alternatively the physical", "alternatively the physical form", "the physical form of the", "physical form of the antigen", "form of the antigen may", "of the antigen may influence", "the antigen may influence its", "antigen may influence its accessibility", "may influence its accessibility to", "influence its accessibility to the", "its accessibility to the endosomal", "accessibility to the endosomal or", "to the endosomal or vacuolar", "the endosomal or vacuolar pathways", "or vacuolar pathways shen", "vacuolar pathways shen et", "pathways shen et al.", "shen et al. 2004 ." ] }, { "record_id": "GLY_000594_1_747", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1237044", "r hsa", "hsa 1237044", "r hsa 1237044" ] }, { "record_id": "GLY_000594_1_747", "filename": "human_protein_pathways_reactome", 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voltage", "influx though voltage activated", "though voltage activated ca2+", "voltage activated ca2+ channels", "ca2+ channels vgcc", "vgcc thereby regulating", "thereby regulating the influx", "regulating the influx of", "the influx of ca2+", "influx of ca2+ flow", "of ca2+ flow via", "ca2+ flow via vgcc.", "ca2+ activated potassium channels are", "activated potassium channels are expressed", "potassium channels are expressed in", "channels are expressed in neuronal", "are expressed in neuronal and", "expressed in neuronal and non", "in neuronal and non neuronal", "neuronal and non neuronal tissue", "and non neuronal tissue such", "non neuronal tissue such as", "neuronal tissue such as smooth", "tissue such as smooth muscle", "as smooth muscle epithelial", "smooth muscle epithelial cell", "muscle epithelial cell and", "epithelial cell and sensory cells.", "cell and sensory cells. ca2+", "and sensory cells. ca2+ activated", "sensory cells. ca2+ activated potassium", "cells. ca2+ activated potassium channels", "activated potassium channels are activated", "potassium channels are activated when", "channels are activated when the", "are activated when the ca2+", "activated when the ca2+ ion", "when the ca2+ ion concentration", "the ca2+ ion concentration increased", "ion concentration increased the", "concentration increased the efflux", "increased the efflux of", "the efflux of k+ via", "efflux of k+ via these", "of k+ via these channels", "k+ via these channels leads", "via these channels leads to", "these channels leads to repolarization/hyperpolarization", "channels leads to repolarization/hyperpolarization of", "leads to repolarization/hyperpolarization of the", "to repolarization/hyperpolarization of the membrane", "repolarization/hyperpolarization of the membrane potential", "of the membrane potential which", "the membrane potential which limits", "membrane potential which limits the", "potential which limits the ca2+", "which limits the ca2+ influx", "limits the ca2+ influx though", "the ca2+ influx though voltage", "ca2+ influx though voltage activated", "influx though voltage activated ca2+", "though voltage activated ca2+ channels", "activated ca2+ channels vgcc", "channels vgcc thereby", "vgcc thereby regulating the", "thereby regulating the influx of", "regulating the influx of ca2+", "the influx of ca2+ flow", "influx of ca2+ flow via", "of ca2+ flow via vgcc." ] }, { "record_id": "GLY_000594_1_753", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1296061", "r hsa", "hsa 1296061", "r hsa 1296061" ] }, { "record_id": "GLY_000594_1_753", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hcn channels", "hyperpolarization activated", "activated cyclic", "cyclic nucleotide", "nucleotide gated", "channels are", "are nonselective", "nonselective ligand", "ligand gated", "gated cation", "cation channels", "channels in", "in the", "the plasma", "plasma membranes", "membranes of", "of heart", "heart and", "and brain", "brain cells.", "cells. hcn", "are sometimes", "sometimes referred", "referred to", "to as", "as \u201cpacemaker", "\u201cpacemaker channels\u201d", "channels\u201d because", "because they", "they help", "help to", "to generate", "generate rhythmic", "rhythmic activity", "activity within", "within groups", "groups of", "cells. they", "they are", "are highly", "highly expressed", "expressed in", "in spontaneously", "spontaneously active", "active cardiac", "cardiac regions", "such as", "as the", "the sinoatrial", "sinoatrial node", "the natural", "natural pacemaker", "pacemaker region", "the atrioventricular", "atrioventricular node", "and the", "the purkinje", "purkinje fibres", "fibres of", "of conduction", "conduction tissue.", "tissue. hcn", "are encoded", "encoded by", "by four", "four genes", "and are", "are widely", "widely expressed", "expressed throughout", "throughout the", "the heart", "the central", "central nervous", "nervous system.", "system. hcn", "are homotetramers", "homotetramers of", "of four", "four subunits", "subunits and", "and conduct", "conduct a", "a na+", "na+ and", "and k+", "k+ current", "current with", "with a", "a permeability", "permeability of", "of 1:4.", "1:4. the", "the mixed", "mixed sodium\u2013potassium", "sodium\u2013potassium current", "current activates", "activates upon", "upon hyperpolarization", "hyperpolarization at", "at voltages", "voltages in", "the diastolic", "diastolic range", "normally from", "from \u221260/\u221270", "\u221260/\u221270 mv", "mv to", "to \u221240", "\u221240 mv", "mv .", ". at", "at the", "the end", "end of", "of a", "a sinoatrial", "sinoatrial action", "action potential", "the membrane", "membrane repolarizes", "repolarizes below", "below \u221240/\u221250", "\u221240/\u221250 mv", "the \\funny", "\\funny current\\", "current\\ is", "is activated", "activated and", "and supplies", "supplies inward", "inward current", "which is", "is responsible", "responsible for", "for starting", "starting the", "diastolic depolarization", "depolarization phase", "by this", "this mechanism", "the funny", "funny current", "current controls", "controls the", "the rate", "rate of", "of spontaneous", "spontaneous activity", "activity of", "of sinoatrial", "sinoatrial myocytes", "hence the", "the cardiac", "cardiac rate.", "rate. hcn", "are involved", "involved in", "in controlling", "controlling the", "the rhythmic", "of pacemaker", "pacemaker current", "current in", "in autorythymic", "autorythymic cells", "cells in", "in heart", "and neuronal", "neuronal processes", "processes such", "as dendritic", "dendritic integration", "integration and", "and synaptic", "synaptic transmission.", "hyperpolarization activated cyclic", "activated cyclic nucleotide", "cyclic nucleotide gated", "gated hcn", "channels are nonselective", "are nonselective ligand", "nonselective ligand gated", "ligand gated cation", "gated cation channels", "cation channels in", "channels in the", "in the plasma", "the plasma membranes", "plasma membranes of", "membranes of heart", "of heart and", "heart and brain", "and brain cells.", "brain cells. hcn", "cells. hcn channels", "hcn channels are", "channels are sometimes", "are sometimes referred", "sometimes referred to", "referred to as", "to as \u201cpacemaker", "as \u201cpacemaker channels\u201d", "\u201cpacemaker channels\u201d because", "channels\u201d because they", "because they help", "they help to", "help to generate", "to generate rhythmic", "generate rhythmic activity", "rhythmic activity within", "activity within groups", "within groups of", "groups of heart", "brain cells. they", "cells. they are", "they are highly", "are highly expressed", "highly expressed in", "expressed in spontaneously", "in spontaneously active", "spontaneously active cardiac", "active cardiac regions", "regions such", "such as the", "as the sinoatrial", "the sinoatrial node", "node san", "san the", "the natural pacemaker", "natural pacemaker region", "the atrioventricular node", "node avn", "avn and", "and the purkinje", "the purkinje fibres", "purkinje fibres of", "fibres of conduction", "of conduction tissue.", "conduction tissue. hcn", "tissue. hcn channels", "channels are encoded", "are encoded by", "encoded by four", "by four genes", "genes hcn1", "hcn1 2", "2 3", "3 4", "4 and", "and are widely", "are widely expressed", "widely expressed throughout", "expressed throughout the", "throughout the heart", "the heart and", "heart and the", "and the central", "the central nervous", "central nervous system.", "nervous system. hcn", "system. hcn channels", "channels are homotetramers", "are homotetramers of", "homotetramers of four", "of four subunits", "four subunits and", "subunits and conduct", "and conduct a", "conduct a na+", "a na+ and", "na+ and k+", "and k+ current", "k+ current with", "current with a", "with a permeability", "a permeability of", "permeability of 1:4.", "of 1:4. the", "1:4. the mixed", "the mixed sodium\u2013potassium", "mixed sodium\u2013potassium current", "sodium\u2013potassium current activates", "current activates upon", "activates upon hyperpolarization", "upon hyperpolarization at", "hyperpolarization at voltages", "at voltages in", "voltages in the", "in the diastolic", "the diastolic range", "range normally", "normally from \u221260/\u221270", "from \u221260/\u221270 mv", "\u221260/\u221270 mv to", "mv to \u221240", "to \u221240 mv", "\u221240 mv .", "mv . at", ". at the", "at the end", "the end of", "end of a", "of a sinoatrial", "a sinoatrial action", "sinoatrial action potential", "potential the", "the membrane repolarizes", "membrane repolarizes below", "repolarizes below \u221240/\u221250", "below \u221240/\u221250 mv", "mv the", "the \\funny current\\", "\\funny current\\ is", "current\\ is activated", "is activated and", "activated and supplies", "and supplies inward", "supplies inward current", "current which", "which is responsible", "is responsible for", "responsible for starting", "for starting the", "starting the diastolic", "the diastolic depolarization", "diastolic depolarization phase", "phase dd", "by this mechanism", "mechanism the", "the funny current", "funny current controls", "current controls the", "controls the rate", "the rate of", "rate of spontaneous", "of spontaneous activity", "spontaneous activity of", "activity of sinoatrial", "of sinoatrial myocytes", "myocytes hence", "hence the cardiac", "the cardiac rate.", "cardiac rate. hcn", "rate. hcn channels", "channels are involved", "are involved in", "involved in controlling", "in controlling the", "controlling the rhythmic", "the rhythmic activity", "rhythmic activity of", "activity of pacemaker", "of pacemaker current", "pacemaker current in", "current in autorythymic", "in autorythymic cells", "autorythymic cells in", "cells in heart", "in heart and", "heart and neuronal", "and neuronal processes", "neuronal processes such", "processes such as", "such as dendritic", "as dendritic integration", "dendritic integration and", "integration and synaptic", "and synaptic transmission.", "hyperpolarization activated cyclic nucleotide", "activated cyclic nucleotide gated", "nucleotide gated hcn", "channels are nonselective ligand", "are nonselective ligand gated", "nonselective ligand gated cation", "ligand gated cation channels", "gated cation channels in", "cation channels in the", "channels in the plasma", "in the plasma membranes", "the plasma membranes of", "plasma membranes of heart", "membranes of heart and", "of heart and brain", "heart and brain cells.", "and brain cells. hcn", "brain cells. hcn channels", "cells. hcn channels are", "hcn channels are sometimes", "channels are sometimes referred", "are sometimes referred to", "sometimes referred to as", "referred to as \u201cpacemaker", "to as \u201cpacemaker channels\u201d", "as \u201cpacemaker channels\u201d because", "\u201cpacemaker channels\u201d because they", "channels\u201d because they help", "because they help to", "they help to generate", "help to generate rhythmic", "to generate rhythmic activity", "generate rhythmic activity within", "rhythmic activity within groups", "activity within groups of", "within groups of heart", "groups of heart and", "and brain cells. they", "brain cells. they are", "cells. they are highly", "they are highly expressed", "are highly expressed in", "highly expressed in spontaneously", "expressed in spontaneously active", "in spontaneously active cardiac", "spontaneously active cardiac regions", "cardiac regions such", "regions such as", "such as the sinoatrial", "as the sinoatrial node", "sinoatrial node san", "san the natural", "the natural pacemaker region", "region the", "atrioventricular node avn", "avn and the", "and the purkinje fibres", "the purkinje fibres of", "purkinje fibres of conduction", "fibres of conduction tissue.", "of conduction tissue. hcn", "conduction tissue. hcn channels", "tissue. hcn channels are", "hcn channels are encoded", "channels are encoded by", "are encoded by four", "encoded by four genes", "four genes hcn1", "4 and are", "and are widely expressed", "are widely expressed throughout", "widely expressed throughout the", "expressed throughout the heart", "throughout the heart and", "the heart and the", "heart and the central", "and the central nervous", "the central nervous system.", "central nervous system. hcn", "nervous system. hcn channels", "system. hcn channels are", "hcn channels are homotetramers", "channels are homotetramers of", "are homotetramers of four", "homotetramers of four subunits", "of four subunits and", "four subunits and conduct", "subunits and conduct a", "and conduct a na+", "conduct a na+ and", "a na+ and k+", "na+ and k+ current", "and k+ current with", "k+ current with a", "current with a permeability", "with a permeability of", "a permeability of 1:4.", "permeability of 1:4. the", "of 1:4. the mixed", "1:4. the mixed sodium\u2013potassium", "the mixed sodium\u2013potassium current", "mixed sodium\u2013potassium current activates", "sodium\u2013potassium current activates upon", "current activates upon hyperpolarization", "activates upon hyperpolarization at", "upon hyperpolarization at voltages", "hyperpolarization at voltages in", "at voltages in the", "voltages in the diastolic", "in the diastolic range", "diastolic range normally", "range normally from", "normally from \u221260/\u221270 mv", "from \u221260/\u221270 mv to", "\u221260/\u221270 mv to \u221240", "mv to \u221240 mv", "to \u221240 mv .", "\u221240 mv . at", "mv . at the", ". at the end", "at the end of", "the end of a", "end of a sinoatrial", "of a sinoatrial action", "a sinoatrial action potential", "action potential the", "potential the membrane", "the membrane repolarizes below", "membrane repolarizes below \u221240/\u221250", "repolarizes below \u221240/\u221250 mv", "\u221240/\u221250 mv the", "mv the \\funny", "the \\funny current\\ is", "\\funny current\\ is activated", "current\\ is activated and", "is activated and supplies", "activated and supplies inward", "and supplies inward current", "inward current which", "current which is", "which is responsible for", "is responsible for starting", "responsible for starting the", "for starting the diastolic", "starting the diastolic depolarization", "the diastolic depolarization phase", "depolarization phase dd", "dd by", "this mechanism the", "mechanism the funny", "the funny current controls", "funny current controls the", "current controls the rate", "controls the rate of", "the rate of spontaneous", "rate of spontaneous activity", "of spontaneous activity of", "spontaneous activity of sinoatrial", "activity of sinoatrial myocytes", "sinoatrial myocytes hence", "myocytes hence the", "hence the cardiac rate.", "the cardiac rate. hcn", "cardiac rate. hcn channels", "rate. hcn channels are", "hcn channels are involved", "channels are involved in", "are involved in controlling", "involved in controlling the", "in controlling the rhythmic", "controlling the rhythmic activity", "the rhythmic activity of", "rhythmic activity of pacemaker", "activity of pacemaker current", "of pacemaker current in", "pacemaker current in autorythymic", "current in autorythymic cells", "in autorythymic cells in", "autorythymic cells in heart", "cells in heart and", "in heart and neuronal", "heart and neuronal processes", "and neuronal processes such", "neuronal processes such as", "processes such as dendritic", "such as dendritic integration", "as dendritic integration and", "dendritic integration and synaptic", "integration and synaptic transmission.", "hyperpolarization activated cyclic nucleotide gated", "cyclic nucleotide gated hcn", "gated hcn channels", "hcn channels are nonselective", "channels are nonselective ligand gated", "are nonselective ligand gated cation", "nonselective ligand gated cation channels", "ligand gated cation channels in", "gated cation channels in the", "cation channels in the plasma", "channels in the plasma membranes", "in the plasma membranes of", "the plasma membranes of heart", "plasma membranes of heart and", "membranes of heart and brain", "of heart and brain cells.", "heart and brain cells. hcn", "and brain cells. hcn channels", "brain cells. hcn channels are", "cells. hcn channels are sometimes", "hcn channels are sometimes referred", "channels are sometimes referred to", "are sometimes referred to as", "sometimes referred to as \u201cpacemaker", "referred to as \u201cpacemaker channels\u201d", "to as \u201cpacemaker channels\u201d because", "as \u201cpacemaker channels\u201d because they", "\u201cpacemaker channels\u201d because they help", "channels\u201d because they help to", "because they help to generate", "they help to generate rhythmic", "help to generate rhythmic activity", "to generate rhythmic activity within", "generate rhythmic activity within groups", "rhythmic activity within groups of", "activity within groups of heart", "within groups of heart and", "groups of heart and brain", "heart and brain cells. they", "and brain cells. they are", "brain cells. they are highly", "cells. they are highly expressed", "they are highly expressed in", "are highly expressed in spontaneously", "highly expressed in spontaneously active", "expressed in spontaneously active cardiac", "in spontaneously active cardiac regions", "active cardiac regions such", "cardiac regions such as", "regions such as the", "such as the sinoatrial node", "the sinoatrial node san", "node san the", "san the natural pacemaker", "pacemaker region the", "region the atrioventricular", "the atrioventricular node avn", "node avn and", "avn and the purkinje", "and the purkinje fibres of", "the purkinje fibres of conduction", "purkinje fibres of conduction tissue.", "fibres of conduction tissue. hcn", "of conduction tissue. hcn channels", "conduction tissue. hcn channels are", "tissue. hcn channels are encoded", "hcn channels are encoded by", "channels are encoded by four", "are encoded by four genes", "by four genes hcn1", "genes hcn1 2", "hcn1 2 3", "2 3 4", "3 4 and", "4 and are widely", "and are widely expressed throughout", "are widely expressed throughout the", "widely expressed throughout the heart", "expressed throughout the heart and", "throughout the heart and the", "the heart and the central", "heart and the central nervous", "and the central nervous system.", "the central nervous system. hcn", "central nervous system. hcn channels", "nervous system. hcn channels are", "system. hcn channels are homotetramers", "hcn channels are homotetramers of", "channels are homotetramers of four", "are homotetramers of four subunits", "homotetramers of four subunits and", "of four subunits and conduct", "four subunits and conduct a", "subunits and conduct a na+", "and conduct a na+ and", "conduct a na+ and k+", "a na+ and k+ current", "na+ and k+ current with", "and k+ current with a", "k+ current with a permeability", "current with a permeability of", "with a permeability of 1:4.", "a permeability of 1:4. the", "permeability of 1:4. the mixed", "of 1:4. the mixed sodium\u2013potassium", "1:4. the mixed sodium\u2013potassium current", "the mixed sodium\u2013potassium current activates", "mixed sodium\u2013potassium current activates upon", "sodium\u2013potassium current activates upon hyperpolarization", "current activates upon hyperpolarization at", "activates upon hyperpolarization at voltages", "upon hyperpolarization at voltages in", "hyperpolarization at voltages in the", "at voltages in the diastolic", "voltages in the diastolic range", "the diastolic range normally", "diastolic range normally from", "range normally from \u221260/\u221270", "normally from \u221260/\u221270 mv to", "from \u221260/\u221270 mv to \u221240", "\u221260/\u221270 mv to \u221240 mv", "mv to \u221240 mv .", "to \u221240 mv . at", "\u221240 mv . at the", "mv . at the end", ". at the end of", "at the end of a", "the end of a sinoatrial", "end of a sinoatrial action", "of a sinoatrial action potential", "sinoatrial action potential the", "action potential the membrane", "potential the membrane repolarizes", "the membrane repolarizes below \u221240/\u221250", "membrane repolarizes below \u221240/\u221250 mv", "below \u221240/\u221250 mv the", "\u221240/\u221250 mv the \\funny", "mv the \\funny current\\", "the \\funny current\\ is activated", "\\funny current\\ is activated and", "current\\ is activated and supplies", "is activated and supplies inward", "activated and supplies inward current", "supplies inward current which", "inward current which is", "current which is responsible", "which is responsible for starting", "is responsible for starting the", "responsible for starting the diastolic", "for starting the diastolic depolarization", "starting the diastolic depolarization phase", "diastolic depolarization phase dd", "dd by this", "by this mechanism the", "this mechanism the funny", "mechanism the funny current", "the funny current controls the", "funny current controls the rate", "current controls the rate of", "controls the rate of spontaneous", "the rate of spontaneous activity", "rate of spontaneous activity of", "of spontaneous activity of sinoatrial", "spontaneous activity of sinoatrial myocytes", "of sinoatrial myocytes hence", "sinoatrial myocytes hence the", "myocytes hence the cardiac", "hence the cardiac rate. hcn", "the cardiac rate. hcn channels", "cardiac rate. hcn channels are", "rate. hcn channels are involved", "hcn channels are involved in", "channels are involved in controlling", "are involved in controlling the", "involved in controlling the rhythmic", "in controlling the rhythmic activity", "controlling the rhythmic activity of", "the rhythmic activity of pacemaker", "rhythmic activity of pacemaker current", "activity of pacemaker current in", "of pacemaker current in autorythymic", "pacemaker current in autorythymic cells", "current in autorythymic cells in", "in autorythymic cells in heart", "autorythymic cells in heart and", "cells in heart and neuronal", "in heart and neuronal processes", "heart and neuronal processes such", "and neuronal processes such as", "neuronal processes such as dendritic", "processes such as dendritic integration", "such as dendritic integration and", "as dendritic integration and synaptic", "dendritic integration and synaptic transmission." ] }, { "record_id": "GLY_000594_1_754", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1296072", "r hsa", "hsa 1296072", "r hsa 1296072" ] }, { "record_id": "GLY_000594_1_754", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "voltage gated", "gated potassium", "potassium channels", "voltage gated potassium", "gated potassium channels", "voltage gated potassium channels", "gated k+", "k+ channels", "determine the", "the excitability", "excitability of", "of heart", "brain and", "and skeletal", "skeletal muscle", "muscle cells.", "cells. kv", "kv form", "form octameric", "octameric channel", "channel with", "with alpha", "alpha subunits", "subunits that", "that forms", "forms the", "the pore", "pore of", "of the", "the channel", "channel and", "and associated", "associated beta", "beta subunits.", "subunits. the", "the alpha", "subunits associate", "associate with", "with beta", "beta subunits", "subunits with", "with a", "a stoichiometry", "stoichiometry of", "of alpha4beta4.the", "alpha4beta4.the alpha", "subunits have", "have been", "been classified", "classified into", "into 12", "12 families", "1 12", "12 with", "with several", "several representatives", "representatives from", "from each", "each family.", "family. members", "members of", "of kv", "kv 1", "1 4", "4 form", "form both", "both homotetramers", "homotetramers and", "and heterotetramers", "kv 5", "5 12", "form functional", "functional heterotetramers.", "heterotetramers. kv's", "kv's are", "are expressed", "expressed in", "in the", "the axon", "at axon", "axon nodes", "somatodendritic sites", "sites and", "and axon", "axon termini.", "voltage gated k+", "gated k+ channels", "channels kv", "kv determine", "determine the excitability", "the excitability of", "excitability of heart", "heart brain", "brain and skeletal", "and skeletal muscle", "skeletal muscle cells.", "muscle cells. kv", "cells. kv form", "kv form octameric", "form octameric channel", "octameric channel with", "channel with alpha", "with alpha subunits", "alpha subunits that", "subunits that forms", "that forms the", "forms the pore", "the pore of", "pore of the", "of the channel", "the channel and", "channel and associated", "and associated beta", "associated beta subunits.", "beta subunits. the", "subunits. the alpha", "the alpha subunits", "alpha subunits associate", "subunits associate with", "associate with beta", "with beta subunits", "beta 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somatodendritic sites", "nodes somatodendritic sites and", "somatodendritic sites and axon termini." ] }, { "record_id": "GLY_000594_1_755", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1299503", "r hsa", "hsa 1299503", "r hsa 1299503" ] }, { "record_id": "GLY_000594_1_755", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "twik related", "related potassium", "potassium channel", "twik related potassium", "related potassium channel", "channel trek", "twik related potassium channel", "potassium channel trek", "related potassium channel trek", "trek1 and", "and trek", "trek 2", "2 are", "are activated", "activated by", "by physiochemical", "physiochemical changes", "changes like", "like stretch", "convex deformation", "deformation of", "of the", "the plasma", "plasma membrane", "heat and", "and intracellular", "intracellular acidosis.", "acidosis. polyunsaturated", "polyunsaturated fatty", 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"depolarization heat and intracellular", "heat and intracellular acidosis. polyunsaturated", "and intracellular acidosis. polyunsaturated fatty", "intracellular acidosis. polyunsaturated fatty acids", "polyunsaturated fatty acids pufa", "acids pufa including", "pufa including arachidonic acid", "including arachidonic acid open trek", "arachidonic acid open trek channels." ] }, { "record_id": "GLY_000594_1_756", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1307965", "r hsa", "hsa 1307965", "r hsa 1307965" ] }, { "record_id": "GLY_000594_1_756", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "betaklotho mediated", "mediated ligand", "ligand binding", "betaklotho mediated ligand", "mediated ligand binding", "betaklotho mediated ligand binding", "fgf21 and", "and fgf19", "fgf19 require", "require betaklotho", "betaklotho for", "for efficient", "efficient signaling", "signaling through", "through 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the", "et al. 2003 .
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the", ".

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while", "

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kininogen", "kallikrein.

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the", "2004 .

the second", ".

the second group", "second group of", "group of events", "events occurs", "occurs in vivo", "in vivo on", "vivo on the", "on the surfaces", "the surfaces of", "surfaces of activated", "of activated platelets", "platelets although", "although most biochemical", "most biochemical characterization", "biochemical characterization of", "characterization of the", "of the reactions", "the reactions was", "reactions was originally", "was originally done", "originally done with", "done with purified", "with purified proteins", "purified proteins in", "proteins in solution", "in solution .", "solution . factor", ". factor xi", "factor xi binds", "xi binds to", "binds to the", "to the platelet", "the platelet glycoprotein", "glycoprotein gp", "gp ib:ix:v", "complex where", "where it can", "it can be", "can be activated", "be activated by", "activated by cleavage", "by cleavage either", "cleavage either by", "either by thrombin", "thrombin generated", "generated by reactions", "by reactions of", "of the common", "the common pathway", "pathway or", "or by activated", "by activated factor", "activated factor xii", "xii generated", "generated in the", "in the first", "the first part", "first part of", "part of the", "intrinsic pathway .", "pathway . activated", ". activated factor", "activated factor xi", "factor xi in", "xi in turn", "in turn catalyzes", "turn catalyzes the", "of factor ix.", "factor ix. simultaneously", "simultaneously factor", "viii complexed", "complexed with vwf", "vwf is", "is cleaved by", "cleaved by thrombin", "thrombin activating", "activating it and", "it and causing", "and causing its", "causing its release", "its release from", "release from vwf.", "from vwf. activated", "vwf. activated factors", "activated factors viii", "and ix form", "ix form a", "form a complex", "a complex on", "complex on the", "on the platelet", "the platelet surface", "platelet surface that", "surface that very", "that very efficiently", "very efficiently converts", "efficiently converts factor", "converts factor x", "factor x to", "x to activated", "to activated factor", "activated factor x.", "x. activated", "activated factors x", "factors x and", "x and v", "and v then", "v then form", "then form a", "a complex that", "complex that efficiently", "that efficiently activates", "efficiently activates thrombin.", "activates thrombin.

while", "thrombin.

while these", "

while these two", "these two groups", "two groups of", "groups of events", "of events can", "events can be", "can be viewed", "be viewed as", "viewed as forming", "as forming a", "forming a single", "a single functional", "single functional pathway", "pathway e.g.", "e.g. davie", "human clinical genetic", "clinical genetic data", "genetic data cast", "data cast doubt", "cast doubt on", "doubt on this", "on this view.", "this view. individuals", "view. individuals deficient", "individuals deficient in", "deficient in kininogen", "prekallikrein or", "or factor xii", "factor xii proteins", "xii proteins exhibit", "proteins exhibit normal", "exhibit normal blood", "normal blood clot", "blood clot formation", "clot formation in", "formation in vivo.", "in vivo. in", "vivo. in contrast", "contrast deficiencies", "deficiencies of factor", "of factor xi", "factor xi can", "xi can be", "can be associated", "be associated with", "associated with failure", "with failure of", "failure of blood", "blood clotting under", "clotting under some", "under some conditions", "conditions and", "and deficiencies of", "deficiencies of vwf", "vwf factor", "viii or", "or factor ix", "factor ix cause", "ix cause severe", "cause severe abnormalities", "von willebrand disease", "disease hemophilia", "a and", "and hemophilia b", "b respectively.", "respectively. these data", "these data suggest", "data suggest that", "suggest that while", "that while the", "while the second", "the second group", "of events is", "events is essential", "is essential for", "essential for normal", "for normal clot", "normal clot formation", "formation in vivo", "vivo the", "the first group", "first group has", "group has a", "has a different", "a different function", "function e.g.", "e.g. schmaier", "schmaier 2004 .

finally", ".

finally reactions", "reactions neutralize proteins", "neutralize proteins activated", "proteins activated in", "activated in the", "the intrinsic pathway.", "intrinsic pathway. kallikrein", "pathway. kallikrein forms", "kallikrein forms stable", "forms stable complexes", "stable complexes with", "complexes with either", "with either c1", "either c1 inhibitor", "inhibitor c1inh", "c1inh or", "or with alpha2", "with alpha2 macroglobulin", "macroglobulin and", "and factor xiia", "factor xiia forms", "xiia forms stable", "complexes with c1inh.", "with c1inh. the", "c1inh. the relevance", "the relevance of", "relevance of these", "of these neutralization", "these neutralization events", "neutralization events to", "events to the", "to the regulation", "the regulation of", "regulation of blood", "blood clotting is", "clotting is unclear", "unclear however.", "however. the physiological", "the physiological abnormalities", "physiological abnormalities observed", "abnormalities observed in", "observed in individuals", "in individuals who", "individuals who lack", "who lack c1inh", "lack c1inh appear", "c1inh appear to", "to be due", "be due entirely", "due entirely to", "entirely to abnormalities", "to abnormalities of", "abnormalities of complement", "of complement activation", "activation blood", "blood clotting appears", "clotting appears to", "appears to proceed", "to proceed normally.", "proceed normally. this", "normally. this observation", "this observation is", "observation is consistent", "is consistent with", "consistent with the", "with the hypothesis", "hypothesis above", "above that", "that factor xiia", "factor xiia plays", "xiia plays a", "plays a limited", "a limited role", "limited role in", "role in normal", "in normal blood", "normal blood clotting", "clotting under physiological", "under physiological conditions.", "the intrinsic pathway of", "intrinsic pathway of blood", "pathway of blood clotting", "of blood clotting connects", "blood clotting connects interactions", "clotting connects interactions among", "connects interactions among kininogen", "among kininogen high", "kininogen high molecular", "high molecular weight kininogen", "weight kininogen hk", "hk prekallikrein", "pk and", "and factor xii to", "factor xii to the", "xii to the activation", "to the activation of", "the activation of clotting", "activation of clotting factor", "of clotting factor x", "clotting factor x by", "factor x by a", "x by a series", "by a series of", "a series of reactions", "series of reactions that", "of reactions that is", "reactions that is independent", "that is independent of", "is independent of the", "independent of the extrinsic", "of the extrinsic pathway", "the extrinsic pathway and", "extrinsic pathway and that", "pathway and that is", "and that is not", "that is not subject", "is not subject to", "not subject to inhibition", "subject to inhibition by", "to inhibition by tfpi.", "inhibition by tfpi. it", "by tfpi. it is", "tfpi. it is thus", "it is thus essential", "is thus essential for", "thus essential for the", "essential for the prolongation", "for the prolongation of", "the prolongation of the", "prolongation of the clotting", "of the clotting cascade:", "the clotting cascade: while", "clotting cascade: while the", "cascade: while the reactions", "while the reactions of", "the reactions of the", "reactions of the extrinsic", "the extrinsic pathway appear", "extrinsic pathway appear to", "pathway appear to be", "appear to be sufficient", "to be sufficient to", "be sufficient to initiate", "sufficient to initiate clot", "to initiate clot formation", "clot formation those", "formation those of", "those of the intrinsic", "of the intrinsic pathway", "the intrinsic pathway are", "intrinsic pathway are required", "pathway are required to", "are required to maintain", "required to maintain it", "maintain it broze", "it broze 1995", "broze 1995 davie", "1995 davie et", "davie et al. 1991", "al. 1991 monroe", "1991 monroe et", "monroe et al. 2002", "et al. 2002 .", "al. 2002 . the", "2002 . the intrinsic", ". the intrinsic pathway", "the intrinsic pathway can", "intrinsic pathway can be", "pathway can be divided", "can be divided into", "be divided into three", "divided into three parts:", "into three parts: 1", "parts: 1 reactions", "1 reactions involving", "reactions involving interactions of", "involving interactions of kininogen", "of kininogen prekallikrein", "prekallikrein and factor", "factor xii leading", "xii leading to", "leading to the activation", "the activation of factor", "activation of factor xii", "factor xii 2", "2 reactions involving", "reactions involving factor xi", "factor xi factor", "xi factor ix", "factor ix factor", "ix factor viii", "factor viii and", "viii and von", "and von willebrand factor", "willebrand factor vwf", "vwf leading to", "the activation of factors", "activation of factors viii", "of factors viii and", "factors viii and ix", "and ix and", "ix and 3", "and 3 reactions", "3 reactions that", "reactions that inactivate factor", "that inactivate factor xiia", "inactivate factor xiia and", "factor xiia and kallikrein.

kininogen", "and kallikrein.

kininogen prekallikrein", "and factor xii were", "factor xii were first", "xii were first identified", "were first identified as", "first identified as proteins", "identified as proteins needed", "as proteins needed for", "proteins needed for the", "needed for the rapid", "for the rapid formation", "the rapid formation of", "rapid formation of clots", "formation of clots when", "of clots when whole", "clots when whole blood", "when whole blood is", "whole blood is exposed", "blood is exposed to", "is exposed to negatively", "exposed to negatively charged", "to negatively charged surfaces", "negatively charged surfaces in", "charged surfaces in vitro.", "surfaces in vitro. early", "in vitro. early studies", "vitro. early studies in", "early studies in vitro", "studies in vitro identified", "in vitro identified several", "vitro identified several possible", "identified several possible sets", "several possible sets of", "possible sets of interactions", "of interactions in", "interactions in which", "in which small quantities", "which small quantities of", "small quantities of one", "quantities of one or", "of one or more", "one or more of", "or more of these", "more of these proteins", "of these proteins 'autoactivate'", "these proteins 'autoactivate' and", "proteins 'autoactivate' and then", "'autoactivate' and then catalyze", "and then catalyze the", "then catalyze the formation", "catalyze the formation of", "the formation of larger", "formation of larger quantities", "of larger quantities of", "larger quantities of activated", "quantities of activated factors.", "of activated factors. subsequent", "activated factors. subsequent work", "subsequent work however", "however suggests that", "suggests that these factors", "that these factors form", "these factors form complexes", "factors form complexes on", "form complexes on endothelial", "complexes on endothelial cell", "on endothelial cell surfaces", "endothelial cell surfaces mediated", "cell surfaces mediated by", "surfaces mediated by c1q", "mediated by c1q binding", "by c1q binding protein", "binding protein c1q", "protein c1q bp", "bp that", "that the first activation", "the first activation event", "first activation event is", "activation event is the", "event is the cleavage", "is the cleavage of", "the cleavage of prekallikrein", "cleavage of prekallikrein by", "of prekallikrein by prolylcarboxypeptidase", "by prolylcarboxypeptidase and", "prolylcarboxypeptidase and that", "and that the resulting", "that the resulting kallikrein", "the resulting kallikrein catalyzes", "resulting kallikrein catalyzes the", "kallikrein catalyzes the activation", "catalyzes the activation of", "factor xii schmaier", "xii schmaier 2004", "schmaier 2004 .

the second", "2004 .

the second group", ".

the second group of", "second group of events", "of events occurs", "events occurs in", "occurs in vivo on", "in vivo on the", "vivo on the surfaces", "on the surfaces of", "the surfaces of activated", "surfaces of activated platelets", "activated platelets although", "platelets although most", "although most biochemical characterization", "most biochemical characterization of", "biochemical characterization of the", "characterization of the reactions", "of the reactions was", "the reactions was originally", "reactions was originally done", "was originally done with", "originally done with purified", "done with purified proteins", "with purified proteins in", "purified proteins in solution", "proteins in solution .", "in solution . factor", "solution . factor xi", ". factor xi binds", "factor xi binds to", "xi binds to the", "binds to the platelet", "to the platelet glycoprotein", "platelet glycoprotein gp", "gp ib:ix:v complex", "ib:ix:v complex where", "complex where it", "where it can be", "it can be activated", "can be activated by", "be activated by cleavage", "activated by cleavage either", "by cleavage either by", "cleavage either by thrombin", "by thrombin generated", "thrombin generated by", "generated by reactions of", "by reactions of the", "reactions of the common", "of the common pathway", "common pathway or", "pathway or by", "or by activated factor", "by activated factor xii", "factor xii generated", "xii generated in", "generated in the first", "in the first part", "the first part of", "first part of the", "part of the intrinsic", "the intrinsic pathway .", "intrinsic pathway . activated", "pathway . activated factor", ". activated factor xi", "activated factor xi in", "factor xi in turn", "xi in turn catalyzes", "in turn catalyzes the", "turn catalyzes the activation", "activation of factor ix.", "of factor ix. simultaneously", "ix. simultaneously factor", "simultaneously factor viii", "factor viii complexed", "viii complexed with", "with vwf is", "vwf is cleaved", "is cleaved by thrombin", "by thrombin activating", "thrombin activating it", "activating it and causing", "it and causing its", "and causing its release", "causing its release from", "its release from vwf.", "release from vwf. activated", "from vwf. activated factors", "vwf. activated factors viii", "activated factors viii and", "viii and ix form", "and ix form a", "ix form a complex", "form a complex on", "a complex on the", "complex on the platelet", "on the platelet surface", "the platelet surface that", "platelet surface that very", "surface that very efficiently", "that very efficiently converts", "very efficiently converts factor", "efficiently converts factor x", "converts factor x to", "factor x to activated", "x to activated factor", "to activated factor x.", "factor x. activated", "x. activated factors", "activated factors x and", "factors x and v", "x and v then", "and v then form", "v then form a", "then form a complex", "form a complex that", "a complex that efficiently", "complex that efficiently activates", "that efficiently activates thrombin.", "efficiently activates thrombin.

while", "activates thrombin.

while these", "thrombin.

while these two", "

while these two groups", "these two groups of", "two groups of events", "groups of events can", "of events can be", "events can be viewed", "can be viewed as", "be viewed as forming", "viewed as forming a", "as forming a single", "forming a single functional", "a single functional pathway", "functional pathway e.g.", "e.g. davie et", "1991 human", "human clinical genetic data", "clinical genetic data cast", "genetic data cast doubt", "data cast doubt on", "cast doubt on this", "doubt on this view.", "on this view. individuals", "this view. individuals deficient", "view. individuals deficient in", "individuals deficient in kininogen", "in kininogen prekallikrein", "prekallikrein or factor", "or factor xii proteins", "factor xii proteins exhibit", "xii proteins exhibit normal", "proteins exhibit normal blood", "exhibit normal blood clot", "normal blood clot formation", "blood clot formation in", "clot formation in vivo.", "formation in vivo. in", "in vivo. in contrast", "in contrast deficiencies", "contrast deficiencies of", "deficiencies of factor xi", "of factor xi can", "factor xi can be", "xi can be associated", "can be associated with", "be associated with failure", "associated with failure of", "with failure of blood", "failure of blood clotting", "of blood clotting under", "blood clotting under some", "clotting under some conditions", "some conditions and", "conditions and deficiencies", "and deficiencies of vwf", "of vwf factor", "vwf factor viii", "factor viii or", "viii or factor", "or factor ix cause", "factor ix cause severe", "ix cause severe abnormalities", "abnormalities von", "willebrand disease hemophilia", "disease hemophilia a", "hemophilia a and", "a and hemophilia", "hemophilia b respectively.", "b respectively. these", "respectively. these data suggest", "these data suggest that", "data suggest that while", "suggest that while the", "that while the second", "while the second group", "the second group of", "group of events is", "of events is essential", "events is essential for", "is essential for normal", "essential for normal clot", "for normal clot formation", "normal clot formation in", "clot formation in vivo", "in vivo the", "vivo the first", "the first group has", "first group has a", "group has a different", "has a different function", "different function e.g.", "e.g. schmaier 2004", "2004 .

finally reactions", ".

finally reactions neutralize", "reactions neutralize proteins activated", "neutralize proteins activated in", "proteins activated in the", "activated in the first", "of the intrinsic pathway.", "the intrinsic pathway. kallikrein", "intrinsic pathway. kallikrein forms", "pathway. kallikrein forms stable", "kallikrein forms stable complexes", "forms stable complexes with", "stable complexes with either", "complexes with either c1", "with either c1 inhibitor", "c1 inhibitor c1inh", "c1inh or with", "or with alpha2 macroglobulin", "alpha2 macroglobulin and", "macroglobulin and factor", "and factor xiia forms", "factor xiia forms stable", "xiia forms stable complexes", "stable complexes with c1inh.", "complexes with c1inh. the", "with c1inh. the relevance", "c1inh. the relevance of", "the relevance of these", "relevance of these neutralization", "of these neutralization events", "these neutralization events to", "neutralization events to the", "events to the regulation", "to the regulation of", "the regulation of blood", "regulation of blood clotting", "of blood clotting is", "blood clotting is unclear", "is unclear however.", "unclear however. the", "however. the physiological abnormalities", "the physiological abnormalities observed", "physiological abnormalities observed in", "abnormalities observed in individuals", "observed in individuals who", "in individuals who lack", "individuals who lack c1inh", "who lack c1inh appear", "lack c1inh appear to", "c1inh appear to be", "appear to be due", "to be due entirely", "be due entirely to", "due entirely to abnormalities", "entirely to abnormalities of", "to abnormalities of complement", "abnormalities of complement activation", "complement activation blood", "activation blood clotting", "blood clotting appears to", "clotting appears to proceed", "appears to proceed normally.", "to proceed normally. this", "proceed normally. this observation", "normally. this observation is", "this observation is consistent", "observation is consistent with", "is consistent with the", "consistent with the hypothesis", "the hypothesis above", "above that factor", "that factor xiia plays", "factor xiia plays a", "xiia plays a limited", "plays a limited role", "a limited role in", "limited role in normal", "role in normal blood", "in normal blood clotting", "normal blood clotting under", "blood clotting under physiological", "clotting under physiological conditions.", "the intrinsic pathway of blood", "intrinsic pathway of blood clotting", "pathway of blood clotting connects", "of blood clotting connects interactions", "blood clotting connects interactions among", "clotting connects interactions among kininogen", "interactions among kininogen high", "among kininogen high molecular", "kininogen high molecular weight", "molecular weight kininogen hk", "pk and factor", "and factor xii to the", "factor xii to the activation", "xii to the activation of", "to the activation of clotting", "the activation of clotting factor", "activation of clotting factor x", "of clotting factor x by", "clotting factor x by a", "factor x by a series", "x by a series of", "by a series of reactions", "a series of reactions that", "series of reactions that is", "of reactions that is independent", "reactions that is independent of", "that is independent of the", "is independent of the extrinsic", "independent of the extrinsic pathway", "of the extrinsic pathway and", "the extrinsic pathway and that", "extrinsic pathway and that is", "pathway and that is not", "and that is not subject", "that is not subject to", "is not subject to inhibition", "not subject to inhibition by", "subject to inhibition by tfpi.", "to inhibition by tfpi. it", "inhibition by tfpi. it is", "by tfpi. it is thus", "tfpi. it is thus essential", "it is thus essential for", "is thus essential for the", "thus essential for the prolongation", "essential for the prolongation of", "for the prolongation of the", "the prolongation of the clotting", "prolongation of the clotting cascade:", "of the clotting cascade: while", "the clotting cascade: while the", "clotting cascade: while the reactions", "cascade: while the reactions of", "while the reactions of the", "the reactions of the extrinsic", "reactions of the extrinsic pathway", "of the extrinsic pathway appear", "the extrinsic pathway appear to", "extrinsic pathway appear to be", "pathway appear to be sufficient", "appear to be sufficient to", "to be sufficient to initiate", "be sufficient to initiate clot", "sufficient to initiate clot formation", "initiate clot formation those", "clot formation those of", "formation those of the", "those of the intrinsic pathway", "of the intrinsic pathway are", "the intrinsic pathway are required", "intrinsic pathway are required to", "pathway are required to maintain", "are required to maintain it", "to maintain it broze", "maintain it broze 1995", "broze 1995 davie et", "1995 davie et al.", "et al. 1991 monroe", "al. 1991 monroe et", "1991 monroe et al.", "monroe et al. 2002 .", "et al. 2002 . the", "al. 2002 . the intrinsic", "2002 . the intrinsic pathway", ". the intrinsic pathway can", "the intrinsic pathway can be", "intrinsic pathway can be divided", "pathway can be divided into", "can be divided into three", "be divided into three parts:", "divided into three parts: 1", "three parts: 1 reactions", "parts: 1 reactions involving", "1 reactions involving interactions", "reactions involving interactions of kininogen", "interactions of kininogen prekallikrein", "kininogen prekallikrein and", "prekallikrein and factor xii", "and factor xii leading", "factor xii leading to", "xii leading to the", "leading to the activation of", "to the activation of factor", "the activation of factor xii", "of factor xii 2", "xii 2 reactions", "2 reactions involving factor", "involving factor xi factor", "factor xi factor ix", "factor ix factor viii", "factor viii and von", "viii and von willebrand", "von willebrand factor vwf", "factor vwf leading", "vwf leading to the", "to the activation of factors", "the activation of factors viii", "activation of factors viii and", "of factors viii and ix", "viii and ix and", "and ix and 3", "and 3 reactions that", "3 reactions that inactivate", "reactions that inactivate factor xiia", "that inactivate factor xiia and", "inactivate factor xiia and kallikrein.

kininogen", "xiia and kallikrein.

kininogen prekallikrein", "kallikrein.

kininogen prekallikrein and", "and factor xii were first", "factor xii were first identified", "xii were first identified as", "were first identified as proteins", "first identified as proteins needed", "identified as proteins needed for", "as proteins needed for the", "proteins needed for the rapid", "needed for the rapid formation", "for the rapid formation of", "the rapid formation of clots", "rapid formation of clots when", "formation of clots when whole", "of clots when whole blood", "clots when whole blood is", "when whole blood is exposed", "whole blood is exposed to", "blood is exposed to negatively", "is exposed to negatively charged", "exposed to negatively charged surfaces", "to negatively charged surfaces in", "negatively charged surfaces in vitro.", "charged surfaces in vitro. early", "surfaces in vitro. early studies", "in vitro. early studies in", "vitro. early studies in vitro", "early studies in vitro identified", "studies in vitro identified several", "in vitro identified several possible", "vitro identified several possible sets", "identified several possible sets of", "several possible sets of interactions", "sets of interactions in", "of interactions in which", "interactions in which small", "in which small quantities of", "which small quantities of one", "small quantities of one or", "quantities of one or more", "of one or more of", "one or more of these", "or more of these proteins", "more of these proteins 'autoactivate'", "of these proteins 'autoactivate' and", "these proteins 'autoactivate' and then", "proteins 'autoactivate' and then catalyze", "'autoactivate' and then catalyze the", "and then catalyze the formation", "then catalyze the formation of", "catalyze the formation of larger", "the formation of larger quantities", "formation of larger quantities of", "of larger quantities of activated", "larger quantities of activated factors.", "quantities of activated factors. subsequent", "of activated factors. subsequent work", "factors. subsequent work however", "work however suggests", "however suggests that these", "suggests that these factors form", "that these factors form complexes", "these factors form complexes on", "factors form complexes on endothelial", "form complexes on endothelial cell", "complexes on endothelial cell surfaces", "on endothelial cell surfaces mediated", "endothelial cell surfaces mediated by", "cell surfaces mediated by c1q", "surfaces mediated by c1q binding", "mediated by c1q binding protein", "c1q binding protein c1q", "binding protein c1q bp", "c1q bp that", "bp that the", "that the first activation event", "the first activation event is", "first activation event is the", "activation event is the cleavage", "event is the cleavage of", "is the cleavage of prekallikrein", "the cleavage of prekallikrein by", "cleavage of prekallikrein by prolylcarboxypeptidase", "prekallikrein by prolylcarboxypeptidase and", "by prolylcarboxypeptidase and that", "prolylcarboxypeptidase and that the", "and that the resulting kallikrein", "that the resulting kallikrein catalyzes", "the resulting kallikrein catalyzes the", "resulting kallikrein catalyzes the activation", "kallikrein catalyzes the activation of", "catalyzes the activation of factor", "of factor xii schmaier", "factor xii schmaier 2004", "xii schmaier 2004 .

the", "schmaier 2004 .

the second group", "2004 .

the second group of", ".

the second group of events", "group of events occurs", "of events occurs in", "events occurs in vivo", "occurs in vivo on the", "in vivo on the surfaces", "vivo on the surfaces of", "on the surfaces of activated", "the surfaces of activated platelets", "of activated platelets although", "activated platelets although most", "platelets although most biochemical", "although most biochemical characterization of", "most biochemical characterization of the", "biochemical characterization of the reactions", "characterization of the reactions was", "of the reactions was originally", "the reactions was originally done", "reactions was originally done with", "was originally done with purified", "originally done with purified proteins", "done with purified proteins in", "with purified proteins in solution", "purified proteins in solution .", "proteins in solution . factor", "in solution . factor xi", "solution . factor xi binds", ". factor xi binds to", "factor xi binds to the", "xi binds to the platelet", "binds to the platelet glycoprotein", "the platelet glycoprotein gp", "glycoprotein gp ib:ix:v", "ib:ix:v complex where it", "complex where it can", "where it can be activated", "it can be activated by", "can be activated by cleavage", "be activated by cleavage either", "activated by cleavage either by", "by cleavage either by thrombin", "either by thrombin generated", "by thrombin generated by", "thrombin generated by reactions", "generated by reactions of the", "by reactions of the common", "reactions of the common pathway", "the common pathway or", "common pathway or by", "pathway or by activated", "or by activated factor xii", "activated factor xii generated", "factor xii generated in", "xii generated in the", "generated in the first part", "in the first part of", "the first part of the", "first part of the intrinsic", "part of the intrinsic pathway", "of the intrinsic pathway .", "the intrinsic pathway . activated", "intrinsic pathway . activated factor", "pathway . activated factor xi", ". activated factor xi in", "activated factor xi in turn", "factor xi in turn catalyzes", "xi in turn catalyzes the", "in turn catalyzes the activation", "turn catalyzes the activation of", "the activation of factor ix.", "activation of factor ix. simultaneously", "factor ix. simultaneously factor", "ix. simultaneously factor viii", "factor viii complexed with", "viii complexed with vwf", "complexed with vwf is", "with vwf is cleaved", "vwf is cleaved by", "cleaved by thrombin activating", "by thrombin activating it", "thrombin activating it and", "activating it and causing its", "it and causing its release", "and causing its release from", "causing its release from vwf.", "its release from vwf. activated", "release from vwf. activated factors", "from vwf. activated factors viii", "vwf. activated factors viii and", "activated factors viii and ix", "factors viii and ix form", "viii and ix form a", "and ix form a complex", "ix form a complex on", "form a complex on the", "a complex on the platelet", "complex on the platelet surface", "on the platelet surface that", "the platelet surface that very", "platelet surface that very efficiently", "surface that very efficiently converts", "that very efficiently converts factor", "very efficiently converts factor x", "efficiently converts factor x to", "converts factor x to activated", "factor x to activated factor", "x to activated factor x.", "activated factor x. activated", "factor x. activated factors", "x. activated factors x", "activated factors x and v", "factors x and v then", "x and v then form", "and v then form a", "v then form a complex", "then form a complex that", "form a complex that efficiently", "a complex that efficiently activates", "complex that efficiently activates thrombin.", "that efficiently activates thrombin.

while", "efficiently activates thrombin.

while these", "activates thrombin.

while these two", "thrombin.

while these two groups", "

while these two groups of", "these two groups of events", "two groups of events can", "groups of events can be", "of events can be viewed", "events can be viewed as", "can be viewed as forming", "be viewed as forming a", "viewed as forming a single", "as forming a single functional", "forming a single functional pathway", "single functional pathway e.g.", "pathway e.g. davie", "e.g. davie et al.", "al. 1991 human", "1991 human clinical", "human clinical genetic data cast", "clinical genetic data cast doubt", "genetic data cast doubt on", "data cast doubt on this", "cast doubt on this view.", "doubt on this view. individuals", "on this view. individuals deficient", "this view. individuals deficient in", "view. individuals deficient in kininogen", "deficient in kininogen prekallikrein", "kininogen prekallikrein or", "prekallikrein or factor xii", "or factor xii proteins exhibit", "factor xii proteins exhibit normal", "xii proteins exhibit normal blood", "proteins exhibit normal blood clot", "exhibit normal blood clot formation", "normal blood clot formation in", "blood clot formation in vivo.", "clot formation in vivo. in", "formation in vivo. in contrast", "vivo. in contrast deficiencies", "in contrast deficiencies of", "contrast deficiencies of factor", "deficiencies of factor xi can", "of factor xi can be", "factor xi can be associated", "xi can be associated with", "can be associated with failure", "be associated with failure of", "associated with failure of blood", "with failure of blood clotting", "failure of blood clotting under", "of blood clotting under some", "blood clotting under some conditions", "under some conditions and", "some conditions and deficiencies", "conditions and deficiencies of", "deficiencies of vwf factor", "of vwf factor viii", "factor viii or factor", "viii or factor ix", "or factor ix cause severe", "factor ix cause severe abnormalities", "severe abnormalities von", "abnormalities von willebrand", "von willebrand disease hemophilia", "willebrand disease hemophilia a", "hemophilia a and hemophilia", "a and hemophilia b", "and hemophilia b respectively.", "hemophilia b respectively. these", "b respectively. these data", "respectively. these data suggest that", "these data suggest that while", "data suggest that while the", "suggest that while the second", "that while the second group", "while the second group of", "the second group of events", "second group of events is", "group of events is essential", "of events is essential for", "events is essential for normal", "is essential for normal clot", "essential for normal clot formation", "for normal clot formation in", "normal clot formation in vivo", "formation in vivo the", "in vivo the first", "vivo the first group", "the first group has a", "first group has a different", "group has a different function", "a different function e.g.", "function e.g. schmaier", "e.g. schmaier 2004 .

finally", "schmaier 2004 .

finally reactions", "2004 .

finally reactions neutralize", ".

finally reactions neutralize proteins", "reactions neutralize proteins activated in", "neutralize proteins activated in the", "proteins activated in the first", "activated in the first part", "part of the intrinsic pathway.", "of the intrinsic pathway. kallikrein", "the intrinsic pathway. kallikrein forms", "intrinsic pathway. kallikrein forms stable", "pathway. kallikrein forms stable complexes", "kallikrein forms stable complexes with", "forms stable complexes with either", "stable complexes with either c1", "complexes with either c1 inhibitor", "either c1 inhibitor c1inh", "inhibitor c1inh or", "c1inh or with alpha2", "with alpha2 macroglobulin and", "alpha2 macroglobulin and factor", "macroglobulin and factor xiia", "and factor xiia forms stable", "factor xiia forms stable complexes", "xiia forms stable complexes with", "forms stable complexes with c1inh.", "stable complexes with c1inh. the", "complexes with c1inh. the relevance", "with c1inh. the relevance of", "c1inh. the relevance of these", "the relevance of these neutralization", "relevance of these neutralization events", "of these neutralization events to", "these neutralization events to the", "neutralization events to the regulation", "events to the regulation of", "to the regulation of blood", "the regulation of blood clotting", "regulation of blood clotting is", "of blood clotting is unclear", "clotting is unclear however.", "is unclear however. the", "unclear however. the physiological", "however. the physiological abnormalities observed", "the physiological abnormalities observed in", "physiological abnormalities observed in individuals", "abnormalities observed in individuals who", "observed in individuals who lack", "in individuals who lack c1inh", "individuals who lack c1inh appear", "who lack c1inh appear to", "lack c1inh appear to be", "c1inh appear to be due", "appear to be due entirely", "to be due entirely to", "be due entirely to abnormalities", "due entirely to abnormalities of", "entirely to abnormalities of complement", "to abnormalities of complement activation", "of complement activation blood", "complement activation blood clotting", "activation blood clotting appears", "blood clotting appears to proceed", "clotting appears to proceed normally.", "appears to proceed normally. this", "to proceed normally. this observation", "proceed normally. this observation is", "normally. this observation is consistent", "this observation is consistent with", "observation is consistent with the", "is consistent with the hypothesis", "with the hypothesis above", "hypothesis above that", "above that factor xiia", "that factor xiia plays a", "factor xiia plays a limited", "xiia plays a limited role", "plays a limited role in", "a limited role in normal", "limited role in normal blood", "role in normal blood clotting", "in normal blood clotting under", "normal blood clotting under physiological", "blood clotting under physiological conditions." ] }, { "record_id": "GLY_000594_1_763", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "140875", "r hsa", "hsa 140875", "r hsa 140875" ] }, { "record_id": "GLY_000594_1_763", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "common pathway", "pathway of", "of fibrin", "fibrin clot", "clot formation", "common pathway of", "pathway of fibrin", "of fibrin clot", "fibrin clot formation", "common pathway of fibrin", "pathway of fibrin clot", "of fibrin clot formation", "common pathway of fibrin clot", "pathway of fibrin clot formation", "the common", "pathway consists", "consists of", "of the", "the cascade", "cascade of", "of activation", "activation events", "events leading", "leading from", "from the", "the formation", "formation of", "of activated", "activated factor", "factor x", "x to", "to the", "of active", "active thrombin", "the cleavage", "cleavage of", "of fibrinogen", "fibrinogen by", "by thrombin", "and 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limiting", "injury while limiting and", "while limiting and physically confining", "limiting and physically confining the", "and physically confining the process.
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these events are outlined in", "events are outlined in the", "are outlined in the drawing:", "outlined in the drawing: black", "in the drawing: black arrows", "the drawing: black arrows connect", "drawing: black arrows connect the", "black arrows connect the substrates", "connect the substrates inputs", "substrates inputs and", "products outputs of", "outputs of individual reactions", "of individual reactions and", "individual reactions and blue", "reactions and blue lines", "and blue lines connect output", "blue lines connect output activated", "lines connect output activated enzymes", "connect output activated enzymes to", "output activated enzymes to the", "activated enzymes to the other", "enzymes to the other reactions", "to the other reactions that", "the other reactions that they", "other reactions that they catalyze." ] }, { "record_id": "GLY_000594_1_764", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1462054", "r hsa", "hsa 1462054", "r hsa 1462054" ] }, { "record_id": "GLY_000594_1_764", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "alpha defensins", "humans have", "have 7", "7 alpha", "alpha defensin", "defensin genes", "genes plus", "plus 5", "5 pseudogenes", "see hgnc", "hgnc at", "at http://www.genenames.org/genefamilies/defa", "http://www.genenames.org/genefamilies/defa .", ". alpha", "defensins have", "have six", "six cysteines", "cysteines linked", "linked 1", "1 6", "2 4", "3 5.", "5. the", "the canonical", "canonical sequence", "sequence of", "of alpha", "defensins in", "in humans", "humans is", "is x1", "x1 2cxcrx2", "2cxcrx2 3cx3ex3gxcx3gx5ccx1", "3cx3ex3gxcx3gx5ccx1 4", "where x", "x represents", "represents any", "any amino", "amino acid", "acid residue.", "residue.
human", "
human alpha", "defensins 1", "1 4", "4 are", "are often", "often called", "called human", "human neutrophil", "neutrophil peptides", "hnp1 4", "as they", "they were", "were initially", "initially identified", "identified in", "in neutrophil", "neutrophil primary", "granules. alpha", "defensins 5", "5 and", "and 6", "are products", "products of", "of paneth", "paneth cells.", "cells. hnp", "hnp 1", "1 and", "3 peptides", "peptides are", "are 30", "30 residues", "residues long", "differing only", "only in", "in the", "the first", "first amino", "amino acid.", "acid. they", "they are", "are encoded", "encoded by", "by the", "the genes", "genes defa1", "defa1 and", "and defa3", "defa3 respectively.", "respectively. these", "these exhibit", "exhibit copy", "copy number", "number polymorphism", "with some", "some individuals", "individuals having", "4 14", "14 copies", "copies per", "per diploid", "while 10", "10 37%", "37% of", "of individuals", "individuals have", "have no", "no copies", "copies of", "of defa3", "aldred et", "et al.", "al. 2005", "linzmier &", "& ganz", "ganz 2005", "ballana et", "al. 2007", "2007 .", ". hnp", "hnp 4", "by defa4", "is 33", "33 amino", "amino acids", "acids long", "long of", "of which", "which 22", "22 differ", "differ from", "from the", "the other", "other hnps", "wilde et", "al. 1989", "1989 .", ". it", "it is", "is a", "a minor", "minor component", "component of", "of neutrophil", "neutrophil granules", "granules compared", "compared to", "to hnp1", "hnp1 3.", "3. in", "in contrast", "contrast to", "to defa1", "genes for", "for hnp", "hd 5", "and hd", "hd 6", "6 are", "are only", "only found", "found as", "as two", "two copies", "diploid genome", "linzmeier &", "2005 .", "hnp 2", "2 is", "is 29", "29 amino", "acids in", "in length", "length and", "and is", "is the", "the proteolytic", "proteolytic product", "product of", "of cleavage", "cleavage of", "of the", "the n", "n terminal", "terminal amino", "acid from", "from either", "either hnp", "1 and/or", "and/or hnp", "hnp 3", "selsted et", "al. 1985", "1985 .", "humans have 7", "have 7 alpha", "7 alpha defensin", "alpha defensin genes", "defensin genes plus", "genes plus 5", "plus 5 pseudogenes", "pseudogenes see", "see hgnc at", "hgnc at http://www.genenames.org/genefamilies/defa", "at http://www.genenames.org/genefamilies/defa .", "http://www.genenames.org/genefamilies/defa . alpha", ". alpha defensins", "alpha defensins have", "defensins have six", "have six cysteines", "six cysteines linked", "cysteines linked 1", "linked 1 6", "6 2", "4 3", "3 5. the", "5. the canonical", "the canonical sequence", "canonical sequence of", "sequence of alpha", "of alpha defensins", "alpha defensins in", "defensins in humans", "in humans is", "humans is x1", "is x1 2cxcrx2", "x1 2cxcrx2 3cx3ex3gxcx3gx5ccx1", "2cxcrx2 3cx3ex3gxcx3gx5ccx1 4", "4 where", "where x represents", "x represents any", "represents any amino", "any amino acid", "amino acid residue.", "acid residue.
human", "residue.
human alpha", "
human alpha defensins", "alpha defensins 1", "defensins 1 4", "1 4 are", "4 are often", "are often called", "often called human", "called human neutrophil", "human neutrophil peptides", "peptides hnp1", "4 as", "as they were", "they were initially", "were initially identified", "initially identified in", "identified in neutrophil", "in neutrophil primary", "primary azurophilic", "azurophilic granules.", "granules. alpha defensins", "alpha defensins 5", "defensins 5 and", "5 and 6", "6 hd5", "hd5 hd6", "hd6 are", "are products of", "products of paneth", "of paneth cells.", "paneth cells. hnp", "cells. hnp 1", "hnp 1 and", "and 3", "3 peptides are", "peptides are 30", "are 30 residues", "30 residues long", "long differing", "differing only in", "only in the", "in the first", "the first amino", "first amino acid.", "amino acid. they", "acid. they are", "they are encoded", "are encoded by", "encoded by the", "by the genes", "the genes defa1", "genes defa1 and", "defa1 and defa3", "and defa3 respectively.", "defa3 respectively. these", "respectively. these exhibit", "these exhibit copy", "exhibit copy number", "copy number polymorphism", "polymorphism with", "with some individuals", "some individuals having", "having 4", "4 14 copies", "14 copies per", "copies per diploid", "genome while", "while 10 37%", "10 37% of", "37% of individuals", "of individuals have", "individuals have no", "have no copies", "no copies of", "copies of defa3", "defa3 aldred", "aldred et al.", "et al. 2005", "2005 linzmier", "linzmier & ganz", "& ganz 2005", "2005 ballana", "ballana et al.", "et al. 2007", "al. 2007 .", "2007 . hnp", ". hnp 4", "4 encoded", "encoded by defa4", "defa4 is", "is 33 amino", "33 amino acids", "amino acids long", "acids long of", "long of which", "of which 22", "which 22 differ", "22 differ from", "differ from the", "from the other", "the other hnps", "hnps wilde", "wilde et al.", "et al. 1989", "al. 1989 .", "1989 . it", ". it is", "it is a", "is a minor", "a minor component", "minor component of", "component of neutrophil", "of neutrophil granules", "neutrophil granules compared", "granules compared to", "compared to hnp1", "to hnp1 3.", "hnp1 3. in", "3. in contrast", "in contrast to", "contrast to defa1", "to defa1 and", "defa3 the", "the genes for", "genes for hnp", "for hnp 4", "4 hd", "hd 5 and", "5 and hd", "and hd 6", "hd 6 are", "6 are only", "are only found", "only found as", "found as two", "as two copies", "two copies per", "per diploid genome", "genome linzmeier", "linzmeier & ganz", "ganz 2005 .", "2005 . hnp", ". hnp 2", "hnp 2 is", "2 is 29", "is 29 amino", "29 amino acids", "amino acids in", "acids in length", "in length and", "length and is", "and is the", "is the proteolytic", "the proteolytic product", "proteolytic product of", "product of cleavage", "of cleavage of", "cleavage of the", "of the n", "the n terminal", "n terminal amino", "terminal amino acid", "amino acid from", "acid from either", "from either hnp", "either hnp 1", "hnp 1 and/or", "1 and/or hnp", "and/or hnp 3", "3 selsted", "selsted et al.", "et al. 1985", "al. 1985 .", "humans have 7 alpha", "have 7 alpha defensin", "7 alpha defensin genes", "alpha defensin genes plus", "defensin genes plus 5", "genes plus 5 pseudogenes", "5 pseudogenes see", "pseudogenes see hgnc", "see hgnc at http://www.genenames.org/genefamilies/defa", "hgnc at http://www.genenames.org/genefamilies/defa .", "at http://www.genenames.org/genefamilies/defa . alpha", "http://www.genenames.org/genefamilies/defa . alpha defensins", ". alpha defensins have", "alpha defensins have six", "defensins have six cysteines", "have six cysteines linked", "six cysteines linked 1", "cysteines linked 1 6", "1 6 2", "6 2 4", "2 4 3", "4 3 5.", "3 5. the canonical", "5. the canonical sequence", "the canonical sequence of", "canonical sequence of alpha", "sequence of alpha defensins", "of alpha defensins in", "alpha defensins in humans", "defensins in humans is", "in humans is x1", "humans is x1 2cxcrx2", "is x1 2cxcrx2 3cx3ex3gxcx3gx5ccx1", "x1 2cxcrx2 3cx3ex3gxcx3gx5ccx1 4", "3cx3ex3gxcx3gx5ccx1 4 where", "4 where x", "where x represents any", "x represents any amino", "represents any amino acid", "any amino acid residue.", "amino acid residue.
human", "acid residue.
human alpha", "residue.
human alpha defensins", "
human alpha defensins 1", "alpha defensins 1 4", "defensins 1 4 are", "1 4 are often", "4 are often called", "are often called human", "often called human neutrophil", "called human neutrophil peptides", "neutrophil peptides hnp1", "peptides hnp1 4", "hnp1 4 as", "4 as they", "as they were initially", "they were initially identified", "were initially identified in", "initially identified in neutrophil", "identified in neutrophil primary", "neutrophil primary azurophilic", "azurophilic granules. alpha", "granules. alpha defensins 5", "alpha defensins 5 and", "defensins 5 and 6", "and 6 hd5", "hd6 are products", "are products of paneth", "products of paneth cells.", "of paneth cells. hnp", "paneth cells. hnp 1", "cells. hnp 1 and", "1 and 3", "and 3 peptides", "3 peptides are 30", "peptides are 30 residues", "are 30 residues long", "residues long differing", "long differing only", "differing only in the", "only in the first", "in the first amino", "the first amino acid.", "first amino acid. they", "amino acid. they are", "acid. they are encoded", "they are encoded by", "are encoded by the", "encoded by the genes", "by the genes defa1", "the genes defa1 and", "genes defa1 and defa3", "defa1 and defa3 respectively.", "and defa3 respectively. these", "defa3 respectively. these exhibit", "respectively. these exhibit copy", "these exhibit copy number", "exhibit copy number polymorphism", "number polymorphism with", "polymorphism with some", "with some individuals having", "individuals having 4", "having 4 14", "4 14 copies per", "14 copies per diploid", "genome while 10", "while 10 37% of", "10 37% of individuals", "37% of individuals have", "of individuals have no", "individuals have no copies", "have no copies of", "no copies of defa3", "of defa3 aldred", "defa3 aldred et", "aldred et al. 2005", "al. 2005 linzmier", "2005 linzmier &", "linzmier & ganz 2005", "ganz 2005 ballana", "2005 ballana et", "ballana et al. 2007", "et al. 2007 .", "al. 2007 . hnp", "2007 . hnp 4", "hnp 4 encoded", "4 encoded by", "by defa4 is", "defa4 is 33", "is 33 amino acids", "33 amino acids long", "amino acids long of", "acids long of which", "long of which 22", "of which 22 differ", "which 22 differ from", "22 differ from the", "differ from the other", "from the other hnps", "other hnps wilde", "hnps wilde et", "wilde et al. 1989", "et al. 1989 .", "al. 1989 . it", "1989 . it is", ". it is a", "it is a minor", "is a minor component", "a minor component of", "minor component of neutrophil", "component of neutrophil granules", "of neutrophil granules compared", "neutrophil granules compared to", "granules compared to hnp1", "compared to hnp1 3.", "to hnp1 3. in", "hnp1 3. in contrast", "3. in contrast to", "in contrast to defa1", "contrast to defa1 and", "to defa1 and defa3", "and defa3 the", "defa3 the genes", "the genes for hnp", "genes for hnp 4", "hnp 4 hd", "4 hd 5", "hd 5 and hd", "5 and hd 6", "and hd 6 are", "hd 6 are only", "6 are only found", "are only found as", "only found as two", "found as two copies", "as two copies per", "two copies per diploid", "copies per diploid genome", "diploid genome linzmeier", "genome linzmeier &", "linzmeier & ganz 2005", "& ganz 2005 .", "ganz 2005 . hnp", "2005 . hnp 2", ". hnp 2 is", "hnp 2 is 29", "2 is 29 amino", "is 29 amino acids", "29 amino acids in", "amino acids in length", "acids in length and", "in length and is", "length and is the", "and is the proteolytic", "is the proteolytic product", "the proteolytic product of", "proteolytic product of cleavage", "product of cleavage of", "of cleavage of the", "cleavage of the n", "of the n terminal", "the n terminal amino", "n terminal amino acid", "terminal amino acid from", "amino acid from either", "acid from either hnp", "from either hnp 1", "either hnp 1 and/or", "hnp 1 and/or hnp", "1 and/or hnp 3", "hnp 3 selsted", "3 selsted et", "selsted et al. 1985", "et al. 1985 .", "humans have 7 alpha defensin", "have 7 alpha defensin genes", "7 alpha defensin genes plus", "alpha defensin genes plus 5", "defensin genes plus 5 pseudogenes", "plus 5 pseudogenes see", "5 pseudogenes see hgnc", "pseudogenes see hgnc at", "see hgnc at http://www.genenames.org/genefamilies/defa .", "hgnc at http://www.genenames.org/genefamilies/defa . alpha", "at http://www.genenames.org/genefamilies/defa . alpha defensins", "http://www.genenames.org/genefamilies/defa . alpha defensins have", ". alpha defensins have six", "alpha defensins have six cysteines", "defensins have six cysteines linked", "have six cysteines linked 1", "six cysteines linked 1 6", "linked 1 6 2", "1 6 2 4", "2 4 3 5.", "4 3 5. the", "3 5. the canonical sequence", "5. the canonical sequence of", "the canonical sequence of alpha", "canonical sequence of alpha defensins", "sequence of alpha defensins in", "of alpha defensins in humans", "alpha defensins in humans is", "defensins in humans is x1", "in humans is x1 2cxcrx2", "humans is x1 2cxcrx2 3cx3ex3gxcx3gx5ccx1", "is x1 2cxcrx2 3cx3ex3gxcx3gx5ccx1 4", "2cxcrx2 3cx3ex3gxcx3gx5ccx1 4 where", "3cx3ex3gxcx3gx5ccx1 4 where x", "4 where x represents", "where x represents any amino", "x represents any amino acid", "represents any amino acid residue.", "any amino acid residue.
human", "amino acid residue.
human alpha", "acid residue.
human alpha defensins", "residue.
human alpha defensins 1", "
human alpha defensins 1 4", "alpha defensins 1 4 are", "defensins 1 4 are often", "1 4 are often called", "4 are often called human", "are often called human neutrophil", "often called human neutrophil peptides", "human neutrophil peptides hnp1", "neutrophil peptides hnp1 4", "hnp1 4 as they", "4 as they were", "as they were initially identified", "they were initially identified in", "were initially identified in neutrophil", "initially identified in neutrophil primary", "in neutrophil primary azurophilic", "primary azurophilic granules.", "azurophilic granules. alpha defensins", "granules. alpha defensins 5 and", "alpha defensins 5 and 6", "5 and 6 hd5", "6 hd5 hd6", "hd5 hd6 are", "hd6 are products of", "are products of paneth cells.", "products of paneth cells. hnp", "of paneth cells. hnp 1", "paneth cells. hnp 1 and", "hnp 1 and 3", "1 and 3 peptides", "and 3 peptides are", "3 peptides are 30 residues", "peptides are 30 residues long", "30 residues long differing", "residues long differing only", "long differing only in", "differing only in the first", "only in the first amino", "in the first amino acid.", "the first amino acid. they", "first amino acid. they are", "amino acid. they are encoded", "acid. they are encoded by", "they are encoded by the", "are encoded by the genes", "encoded by the genes defa1", "by the genes defa1 and", "the genes defa1 and defa3", "genes defa1 and defa3 respectively.", "defa1 and defa3 respectively. these", "and defa3 respectively. these exhibit", "defa3 respectively. these exhibit copy", "respectively. these exhibit copy number", "these exhibit copy number polymorphism", "copy number polymorphism with", "number polymorphism with some", "polymorphism with some individuals", "some individuals having 4", "individuals having 4 14", "having 4 14 copies", "4 14 copies per diploid", "diploid genome while", "genome while 10 37%", "while 10 37% of individuals", "10 37% of individuals have", "37% of individuals have no", "of individuals have no copies", "individuals have no copies of", "have no copies of defa3", "copies of defa3 aldred", "of defa3 aldred et", "defa3 aldred et al.", "et al. 2005 linzmier", "al. 2005 linzmier &", "2005 linzmier & ganz", "& ganz 2005 ballana", "ganz 2005 ballana et", "2005 ballana et al.", "ballana et al. 2007 .", "et al. 2007 . hnp", "al. 2007 . hnp 4", ". hnp 4 encoded", "hnp 4 encoded by", "4 encoded by defa4", "encoded by defa4 is", "by defa4 is 33", "defa4 is 33 amino", "is 33 amino acids long", "33 amino acids long of", "amino acids long of which", "acids long of which 22", "long of which 22 differ", "of which 22 differ from", "which 22 differ from the", "22 differ from the other", "differ from the other hnps", "the other hnps wilde", "other hnps wilde et", "hnps wilde et al.", "wilde et al. 1989 .", "et al. 1989 . it", "al. 1989 . it is", "1989 . it is a", ". it is a minor", "it is a minor component", "is a minor component of", "a minor component of neutrophil", "minor component of neutrophil granules", "component of neutrophil granules compared", "of neutrophil granules compared to", "neutrophil granules compared to hnp1", "granules compared to hnp1 3.", "compared to hnp1 3. in", "to hnp1 3. in contrast", "hnp1 3. in contrast to", "3. in contrast to defa1", "in contrast to defa1 and", "contrast to defa1 and defa3", "defa1 and defa3 the", "and defa3 the genes", "defa3 the genes for", "the genes for hnp 4", "for hnp 4 hd", "hnp 4 hd 5", "4 hd 5 and", "hd 5 and hd 6", "5 and hd 6 are", "and hd 6 are only", "hd 6 are only found", "6 are only found as", "are only found as two", "only found as two copies", "found as two copies per", "as two copies per diploid", "two copies per diploid genome", "per diploid genome linzmeier", "diploid genome linzmeier &", "genome linzmeier & ganz", "linzmeier & ganz 2005 .", "& ganz 2005 . hnp", "ganz 2005 . hnp 2", "2005 . hnp 2 is", ". hnp 2 is 29", "hnp 2 is 29 amino", "2 is 29 amino acids", "is 29 amino acids in", "29 amino acids in length", "amino acids in length and", "acids in length and is", "in length and is the", "length and is the proteolytic", "and is the proteolytic product", "is the proteolytic product of", "the proteolytic product of cleavage", "proteolytic product of cleavage of", "product of cleavage of the", "of cleavage of the n", "cleavage of the n terminal", "of the n terminal amino", "the n terminal amino acid", "n terminal amino acid from", "terminal amino acid from either", "amino acid from either hnp", "acid from either hnp 1", "from either hnp 1 and/or", "either hnp 1 and/or hnp", "hnp 1 and/or hnp 3", "and/or hnp 3 selsted", "hnp 3 selsted et", "3 selsted et al.", "selsted et al. 1985 ." ] }, { "record_id": "GLY_000594_1_765", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1474151", "r hsa", "hsa 1474151", "r hsa 1474151" ] }, { "record_id": "GLY_000594_1_765", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "salvage and", "and regulation", "tetrahydrobiopterin bh4", "bh4 synthesis", "synthesis recycling", "recycling salvage", "salvage and regulation", "recycling salvage and", "tetrahydrobiopterin bh4 synthesis", "bh4 synthesis recycling", "synthesis recycling salvage", "recycling salvage and regulation", "is an", "an essential", "essential co", "co factor", "factor for", "for the", "the aromatic", "aromatic amino", "amino acid", "acid hydroxylases", "hydroxylases and", "and glycerol", "glycerol ether", "ether monooxygenase", "monooxygenase and", "and it", "it regulates", "regulates nitric", "nitric oxide", "oxide synthase", "activity. inherited", "inherited bh4", "bh4 deficiency", "deficiency leads", "leads to", "to hyperphenylalaninemia", "and dopamine", "dopamine and", "and neurotransmitter", "neurotransmitter deficiency", "deficiency in", "in the", "the brain.", "brain. bh4", "bh4 maintains", "maintains enzymatic", "enzymatic coupling", "coupling to", "to l", "l 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these reactive", "reactive oxygen", "oxygen species", "superoxide and", "and peroxynitrite", "can contribute", "contribute to", "to increased", "increased oxidative", "oxidative stress", "stress in", "the endothelium", "endothelium leading", "leading to", "to atherosclerosis", "atherosclerosis and", "and hypertension", "thony et", "et al.", "al. 2000", "crabtree and", "and channon", "channon 2011", "2011 schulz", "schulz et", "al. 2008", "schmidt and", "and alp", "alp 2007", "2007 .", "the synthesis", "recycling and", "and effects", "effects of", "bh4 are", "are shown", "shown here.", "here. three", "three enzymes", "enzymes are", "are required", "required for", "the de", "de novo", "novo biosynthesis", "biosynthesis of", "bh4 and", "and two", "two enzymes", "enzymes for", "the recycling", "recycling of", "of bh4.", "bh4 is", "is an essential", "an essential co", "essential co factor", "co factor for", "factor for the", "for the aromatic", "the aromatic amino", "aromatic amino acid", "amino acid hydroxylases", "acid hydroxylases and", "hydroxylases and glycerol", "and glycerol ether", "glycerol ether monooxygenase", "ether monooxygenase and", "monooxygenase and it", "and it regulates", "it regulates nitric", "regulates nitric oxide", "nitric oxide synthase", "synthase nos", "nos activity.", "activity. inherited bh4", "inherited bh4 deficiency", "bh4 deficiency leads", "deficiency leads to", "leads to hyperphenylalaninemia", "hyperphenylalaninemia and", "and dopamine and", "dopamine and neurotransmitter", "and neurotransmitter deficiency", "neurotransmitter deficiency in", "deficiency in the", "in the brain.", "the brain. bh4", "brain. bh4 maintains", "bh4 maintains enzymatic", "maintains enzymatic coupling", "enzymatic coupling to", "coupling to l", "to l arginine", "l arginine oxidation", "arginine oxidation to", "oxidation to produce", "to produce no.", "produce no. oxidation", "no. oxidation of", "oxidation of bh4", "of bh4 to", "bh4 to bh2", "to bh2 results", "bh2 results in", "results in nos", "in nos uncoupling", "uncoupling resulting", "resulting in superoxide", "superoxide o2.", "formation rather than", "rather than no.", "than no. superoxide", "no. superoxide rapidly", "superoxide rapidly reacts", "rapidly reacts with", "reacts with no", "with no to", "no to produce", "to produce peroxynitrite", "produce peroxynitrite which", "peroxynitrite which can", "which can further", "can further uncouple", "further uncouple nos.
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these reactive", "nos.
these reactive oxygen", "reactive oxygen species", "species superoxide", "superoxide and peroxynitrite", "peroxynitrite can", "can contribute to", "contribute to increased", "to increased oxidative", "increased oxidative stress", "oxidative stress in", "stress in the", "in the endothelium", "the endothelium leading", "endothelium leading to", "leading to atherosclerosis", "to atherosclerosis and", "atherosclerosis and hypertension", "hypertension thony", "thony et al.", "et al. 2000", "2000 crabtree", "crabtree and channon", "and channon 2011", "channon 2011 schulz", "2011 schulz et", "schulz et al.", "et al. 2008", "2008 schmidt", "schmidt and alp", "and alp 2007", "alp 2007 .", ". the", "recycling and effects", "and effects of", "effects of bh4", "of bh4 are", "bh4 are shown", "are shown here.", "shown here. three", "here. three enzymes", "three enzymes are", "enzymes are required", "are required for", "required for the", "for the de", "the de novo", "de novo biosynthesis", "novo biosynthesis of", "biosynthesis of bh4", "of bh4 and", "bh4 and two", "and two enzymes", "two enzymes for", "enzymes for the", "for the recycling", "the recycling of", "recycling of bh4.", "bh4 is an", "is an essential co", "an essential co factor", "essential co factor for", "co factor for the", "factor for the aromatic", "for the aromatic amino", "the aromatic amino acid", "aromatic amino acid hydroxylases", "amino acid hydroxylases and", "acid hydroxylases and glycerol", "hydroxylases and glycerol ether", "and glycerol ether monooxygenase", "glycerol ether monooxygenase and", "ether monooxygenase and it", "monooxygenase and it regulates", "and it regulates nitric", "it regulates nitric oxide", "regulates nitric oxide synthase", "oxide synthase nos", "nos activity. inherited", "activity. inherited bh4 deficiency", "inherited bh4 deficiency leads", "bh4 deficiency leads to", "deficiency leads to hyperphenylalaninemia", "to hyperphenylalaninemia and", "hyperphenylalaninemia and dopamine", "and dopamine and neurotransmitter", "dopamine and neurotransmitter deficiency", "and neurotransmitter deficiency in", "neurotransmitter deficiency in the", "deficiency in the brain.", "in the brain. bh4", "the brain. bh4 maintains", "brain. bh4 maintains enzymatic", "bh4 maintains enzymatic coupling", "maintains enzymatic coupling to", "enzymatic coupling to l", "coupling to l arginine", "to l arginine oxidation", "l arginine oxidation to", "arginine oxidation to produce", "oxidation to produce no.", "to produce no. oxidation", "produce no. oxidation of", "no. oxidation of bh4", "oxidation of bh4 to", "of bh4 to bh2", "bh4 to bh2 results", "to bh2 results in", "bh2 results in nos", "results in nos uncoupling", "nos uncoupling resulting", "uncoupling resulting in", "in superoxide o2.", "o2. formation", "formation rather than no.", "rather than no. superoxide", "than no. superoxide rapidly", "no. superoxide rapidly reacts", "superoxide rapidly reacts with", "rapidly reacts with no", "reacts with no to", "with no to produce", "no to produce peroxynitrite", "to produce peroxynitrite which", "produce peroxynitrite which can", "peroxynitrite which can further", "which can further uncouple", "can further uncouple nos.
these", "further uncouple nos.
these reactive", "uncouple nos.
these reactive oxygen", "nos.
these reactive oxygen species", "oxygen species superoxide", "species superoxide and", "and peroxynitrite can", "peroxynitrite can contribute", "can contribute to increased", "contribute to increased oxidative", "to increased oxidative stress", "increased oxidative stress in", "oxidative stress in the", "stress in the endothelium", "in the endothelium leading", "the endothelium leading to", "endothelium leading to atherosclerosis", "leading to atherosclerosis and", "to atherosclerosis and hypertension", "and hypertension thony", "hypertension thony et", "thony et al. 2000", "al. 2000 crabtree", "2000 crabtree and", "crabtree and channon 2011", "and channon 2011 schulz", "channon 2011 schulz et", "2011 schulz et al.", "schulz et al. 2008", "al. 2008 schmidt", "2008 schmidt and", "schmidt and alp 2007", "and alp 2007 .", "2007 . the", ". the synthesis", "the synthesis recycling", "synthesis recycling and", "recycling and effects of", "and effects of bh4", "effects of bh4 are", "of bh4 are shown", "bh4 are shown here.", "are shown here. three", "shown here. three enzymes", "here. three enzymes are", "three enzymes are required", "enzymes are required for", "are required for the", "required for the de", "for the de novo", "the de novo biosynthesis", "de novo biosynthesis of", "novo biosynthesis of bh4", "biosynthesis of bh4 and", "of bh4 and two", "bh4 and two enzymes", "and two enzymes for", "two enzymes for the", "enzymes for the recycling", "for the recycling of", "the recycling of bh4.", "tetrahydrobiopterin bh4 is", "bh4 is an essential", "is an essential co factor", "an essential co factor for", "essential co factor for the", "co factor for the aromatic", "factor for the aromatic amino", "for the aromatic amino acid", "the aromatic amino acid hydroxylases", "aromatic amino acid hydroxylases and", "amino acid hydroxylases and glycerol", "acid hydroxylases and glycerol ether", "hydroxylases and glycerol ether monooxygenase", "and glycerol ether monooxygenase and", "glycerol ether monooxygenase and it", "ether monooxygenase and it regulates", "monooxygenase and it regulates nitric", "and it regulates nitric oxide", "it regulates nitric oxide synthase", "nitric oxide synthase nos", "synthase nos activity.", "nos activity. inherited bh4", "activity. inherited bh4 deficiency leads", "inherited bh4 deficiency leads to", "bh4 deficiency leads to hyperphenylalaninemia", "leads to hyperphenylalaninemia and", "to hyperphenylalaninemia and dopamine", "hyperphenylalaninemia and dopamine and", "and dopamine and neurotransmitter deficiency", "dopamine and neurotransmitter deficiency in", "and neurotransmitter deficiency in the", "neurotransmitter deficiency in the brain.", "deficiency in the brain. bh4", "in the brain. bh4 maintains", "the brain. bh4 maintains enzymatic", "brain. bh4 maintains enzymatic coupling", "bh4 maintains enzymatic coupling to", "maintains enzymatic coupling to l", "enzymatic coupling to l arginine", "coupling to l arginine oxidation", "to l arginine oxidation to", "l arginine oxidation to produce", "arginine oxidation to produce no.", "oxidation to produce no. oxidation", "to produce no. oxidation of", "produce no. oxidation of bh4", "no. oxidation of bh4 to", "oxidation of bh4 to bh2", "of bh4 to bh2 results", "bh4 to bh2 results in", "to bh2 results in nos", "bh2 results in nos uncoupling", "in nos uncoupling resulting", "nos uncoupling resulting in", "uncoupling resulting in superoxide", "resulting in superoxide o2.", "o2. formation rather", "formation rather than no. superoxide", "rather than no. superoxide rapidly", "than no. superoxide rapidly reacts", "no. superoxide rapidly reacts with", "superoxide rapidly reacts with no", "rapidly reacts with no to", "reacts with no to produce", "with no to produce peroxynitrite", "no to produce peroxynitrite which", "to produce peroxynitrite which can", "produce peroxynitrite which can further", "peroxynitrite which can further uncouple", "which can further uncouple nos.
these", "can further uncouple nos.
these reactive", "further uncouple nos.
these reactive oxygen", "uncouple nos.
these reactive oxygen species", "reactive oxygen species superoxide", "oxygen species superoxide and", "species superoxide and peroxynitrite", "superoxide and peroxynitrite can", "and peroxynitrite can contribute", "peroxynitrite can contribute to", "can contribute to increased oxidative", "contribute to increased oxidative stress", "to increased oxidative stress in", "increased oxidative stress in the", "oxidative stress in the endothelium", "stress in the endothelium leading", "in the endothelium leading to", "the endothelium leading to atherosclerosis", "endothelium leading to atherosclerosis and", "leading to atherosclerosis and hypertension", "atherosclerosis and hypertension thony", "and hypertension thony et", "hypertension thony et al.", "et al. 2000 crabtree", "al. 2000 crabtree and", "2000 crabtree and channon", "crabtree and channon 2011 schulz", "and channon 2011 schulz et", "channon 2011 schulz et al.", "2011 schulz et al. 2008", "et al. 2008 schmidt", "al. 2008 schmidt and", "2008 schmidt and alp", "schmidt and alp 2007 .", "alp 2007 . the", "2007 . the synthesis", "the synthesis recycling and", "synthesis recycling and effects", "recycling and effects of bh4", "and effects of bh4 are", "effects of bh4 are shown", "of bh4 are shown here.", "bh4 are shown here. three", "are shown here. three enzymes", "shown here. three enzymes are", "here. three enzymes are required", "three enzymes are required for", "enzymes are required for the", "are required for the de", "required for the de novo", "for the de novo biosynthesis", "the de novo biosynthesis of", "de novo biosynthesis of bh4", "novo biosynthesis of bh4 and", "biosynthesis of bh4 and two", "of bh4 and two enzymes", "bh4 and two enzymes for", "and two enzymes for the", "two enzymes for the recycling", "enzymes for the recycling of", "for the recycling of bh4." ] }, { "record_id": "GLY_000594_1_766", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1474244", "r hsa", "hsa 1474244", "r hsa 1474244" ] }, { "record_id": "GLY_000594_1_766", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "extracellular matrix", "matrix organization", "extracellular matrix organization", "the extracellular", "matrix is", "is a", "a component", "component of", "of all", "all mammalian", "mammalian tissues", "a network", "network consisting", "consisting largely", "largely of", "of the", "the fibrous", "fibrous proteins", "proteins collagen", "elastin and", "and associated", "associated microfibrils", "fibronectin and", "and laminins", "laminins embedded", "embedded in", "in a", "a viscoelastic", "viscoelastic gel", "gel of", "of anionic", "anionic proteoglycan", "proteoglycan polymers.", "polymers. it", "it performs", "performs many", "many functions", "functions in", "in addition", "addition to", "to its", "its structural", "structural role", "as a", "a major", "major component", "the cellular", "cellular microenvironment", "microenvironment it", "it influences", "influences cell", "cell behaviours", "behaviours such", "such as", "as proliferation", "adhesion and", "and migration", "and regulates", "regulates cell", "cell differentiation", "differentiation and", "and death", "hynes 2009", "2009 .", ".

ecm", "

ecm composition", "composition is", "is highly", "highly heterogeneous", "heterogeneous and", "and dynamic", "being constantly", "constantly remodeled", "frantz et", "et al.", "al. 2010", "and modulated", "largely by", "by matrix", "matrix metalloproteinases", "and growth", "growth factors", "factors that", "that bind", "bind to", "to the", "the ecm", "ecm influencing", "influencing the", "the synthesis", "crosslinking and", "and degradation", "degradation of", "of ecm", "ecm components", ". ecm", "ecm remodeling", "remodeling is", "is involved", "involved in", "in the", "the regulation", "regulation of", "of cell", "differentiation processes", "processes such", "as the", "the establishment", "establishment and", "and maintenance", "maintenance of", "of stem", "stem cell", "cell niches", "branching morphogenesis", "bone remodeling", "and wound", "wound repair.", "repair. redundant", "redundant mechanisms", "mechanisms modulate", "modulate the", "the expression", "expression and", "and function", "function of", "ecm modifying", "modifying enzymes.", "enzymes. abnormal", "abnormal ecm", "ecm dynamics", "dynamics can", "can lead", "lead to", "to deregulated", "deregulated cell", "cell proliferation", "proliferation and", "and invasion", "failure of", "cell death", "and loss", "loss of", "resulting in", "in congenital", "congenital defects", "defects and", "and pathological", "pathological processes", "processes including", "including tissue", "tissue fibrosis", "fibrosis and", "and cancer.

collagen", "cancer.

collagen is", "is the", "the most", "most abundant", "abundant fibrous", "fibrous protein", "protein within", "within the", "ecm constituting", "constituting up", "up to", "to 30%", "30% of", "of total", "total protein", "protein in", "in multicellular", "multicellular animals.", "animals. collagen", "collagen provides", "provides tensile", "tensile strength.", "strength. it", "it associates", "associates with", "with elastic", "elastic fibres", "composed of", "of elastin", "and fibrillin", "fibrillin microfibrils", "which give", "give tissues", "tissues the", "the ability", "ability to", "to recover", "recover after", "after stretching.", "stretching. other", "other ecm", "ecm proteins", "proteins such", "as fibronectin", "and matricellular", "matricellular proteins", "proteins participate", "participate as", "as connectors", "connectors or", "or linking", "linking proteins", "daley et", "al. 2008", "2008 .

chondroitin", ".

chondroitin sulfate", "dermatan sulfate", "sulfate and", "and keratan", "keratan sulfate", "sulfate proteoglycans", "proteoglycans are", "are structural", "structural components", "components associated", "associated with", "with collagen", "collagen fibrils", "scott &", "& haigh", "haigh 1985", "& orford", "orford 1981", "serving to", "to tether", "tether the", "the fibril", "fibril to", "the surrounding", "surrounding matrix.", "matrix. decorin", "decorin belongs", "belongs to", "the small", "small leucine", "leucine rich", "rich repeat", "repeat proteoglycan", "proteoglycan family", "which also", "also includes", "includes biglycan", "lumican and", "and asporin.", "asporin. all", "all appear", "appear to", "to be", "be involved", "in collagen", "collagen fibril", "fibril formation", "formation and", "and matrix", "matrix assembly", "ameye &", "& young", "young 2002", "2002 .", "

ecm proteins", "as osteonectin", "osteopontin and", "and thrombospondins", "1 and", "collectively referred", "referred to", "to as", "as matricellular", "reviewed in", "in mosher", "mosher &", "& adams", "adams 2012", "to modulate", "modulate cell", "cell matrix", "matrix interactions.", "interactions. in", "in general", "general they", "they induce", "induce de", "de adhesion", "characterized by", "by disruption", "disruption of", "of focal", "focal adhesions", "adhesions and", "and a", "a reorganization", "reorganization of", "of actin", "actin stress", "stress fibers", "bornstein 2009", "2 bind", "bind mmp2.", "mmp2. the", "the resulting", "resulting complex", "complex is", "is endocytosed", "endocytosed by", "by the", "the low", "low density", "density lipoprotein", "lipoprotein receptor", "receptor related", "related protein", "clearing mmp2", "mmp2 from", "from the", "yang et", "al. 2001", "2001 .

osteopontin", "bone sialoprotein", "sialoprotein 1", "interacts with", "collagen and", "and fibronectin", "mukherjee et", "al. 1995", "1995 .", ". it", "it also", "also contains", "contains several", "several cell", "cell adhesive", "adhesive domains", "domains that", "that interact", "interact with", "with integrins", "integrins and", "and cd44.

aggrecan", "cd44.

aggrecan is", "the predominant", "predominant ecm", "ecm proteoglycan", "proteoglycan in", "in cartilage", "hardingham &", "& fosang", "fosang 1992", "1992 .", ". its", "its relatives", "relatives include", "include versican", "neurocan and", "and brevican", "iozzo 1998", "1998 .", ". in", "in articular", "articular cartilage", "cartilage the", "the major", "major non", "non fibrous", "fibrous macromolecules", "macromolecules are", "are aggrecan", "hyaluronan and", "and hyaluronan", "and proteoglycan", "proteoglycan link", "link protein", "protein 1", "hapln1 .", ". the", "the high", "high negative", "negative charge", "charge density", "density of", "of these", "these molecules", "molecules leads", "leads to", "the binding", "binding of", "of large", "large amounts", "amounts of", "of water", "bruckner 2006", "2006 .", ". hyaluronan", "hyaluronan is", "is bound", "bound by", "by several", "several large", "large proteoglycans", "proteoglycans proteoglycans", "proteoglycans belonging", "belonging to", "the hyalectan", "hyalectan family", "family that", "that form", "form high", "high molecular", "molecular weight", "weight aggregates", "roughley 2006", "accounting for", "for the", "the turgid", "turgid nature", "nature of", "cartilage.

the", "

the most", "most significant", "significant enzymes", "enzymes in", "in ecm", "remodeling are", "are the", "the matrix", "matrix metalloproteinase", "a disintegrin", "disintegrin and", "and metalloproteinase", "metalloproteinase with", "with thrombospondin", "thrombospondin motifs", "cawston &", "young 2010", "2010 .", ". other", "other notable", "notable ecm", "ecm degrading", "degrading enzymes", "enzymes include", "include plasmin", "plasmin and", "and cathepsin", "cathepsin g.", "g. many", "many ecm", "ecm proteinases", "proteinases are", "are initially", "initially present", "present as", "as precursors", "activated by", "by proteolytic", "proteolytic processing.", "processing. mmp", "mmp precursors", "precursors include", "include an", "an amino", "amino prodomain", "prodomain which", "which masks", "masks the", "the catalytic", "catalytic zn", "zn binding", "binding motif", "page mccawet", "mccawet al.", "al. 2007", "2007 .", ". this", "this can", "can be", "be removed", "removed by", "by other", "other proteinases", "often other", "other mmps.", "mmps. ecm", "proteinases can", "be inactivated", "inactivated by", "by degradation", "or blocked", "blocked by", "by inhibitors.", "inhibitors. some", "some of", "these inhibitors", "including alpha2", "alpha2 macroglobulin", "alpha1 proteinase", "proteinase inhibitor", "and alpha1", "alpha1 chymotrypsin", "chymotrypsin can", "can inhibit", "inhibit a", "a large", "large variety", "variety of", "of proteinases", "woessner &", "& nagase", "nagase 2000", "2000 .", "the tissue", "tissue inhibitors", "inhibitors of", "of metalloproteinases", "are potent", "potent mmp", "mmp inhibitors", "brew &", "nagase 2010", "the extracellular matrix", "extracellular matrix is", "matrix is a", "is a component", "a component of", "component of all", "of all mammalian", "all mammalian tissues", "tissues a", "a network consisting", "network consisting largely", "consisting largely of", "largely of the", "of the fibrous", "the fibrous proteins", "fibrous proteins collagen", "collagen elastin", "elastin and associated", "and associated microfibrils", "microfibrils fibronectin", "fibronectin and laminins", "and laminins embedded", "laminins embedded in", "embedded in a", "in a viscoelastic", "a viscoelastic gel", "viscoelastic gel of", "gel of anionic", "of anionic proteoglycan", "anionic proteoglycan polymers.", "proteoglycan polymers. it", "polymers. it performs", "it performs many", "performs many functions", "many functions in", "functions in addition", "in addition to", "addition to its", "to its structural", "its structural role", "role as", "as a major", "a major component", "major component of", "component of the", "of the cellular", "the cellular microenvironment", "cellular microenvironment it", "microenvironment it influences", "it influences cell", "influences cell behaviours", "cell behaviours such", "behaviours such as", "such as proliferation", "proliferation adhesion", "adhesion and migration", "migration and", "and regulates cell", "regulates cell differentiation", "cell differentiation and", "differentiation and death", "death hynes", "hynes 2009 .", "2009 .

ecm", ".

ecm composition", "

ecm composition is", "composition is highly", "is highly heterogeneous", "highly heterogeneous and", "heterogeneous and dynamic", "dynamic being", "being constantly remodeled", "remodeled frantz", "frantz et al.", "et al. 2010", "2010 and", "modulated largely", "largely by matrix", "by matrix metalloproteinases", "metalloproteinases mmps", "mmps and", "and growth factors", "growth factors that", "factors that bind", "that bind to", "bind to the", "to the ecm", "the ecm influencing", "ecm influencing the", "influencing the synthesis", "synthesis crosslinking", "crosslinking and degradation", "and degradation of", "degradation of ecm", "of ecm components", "components hynes", "2009 . ecm", ". ecm remodeling", "ecm remodeling is", "remodeling is involved", "is involved in", "involved in the", "in the regulation", "the regulation of", "regulation of cell", "of cell differentiation", "cell differentiation processes", "differentiation processes such", "processes such as", "such as the", "as the establishment", "the establishment and", "establishment and maintenance", "and maintenance of", "maintenance of stem", "of stem cell", "stem cell niches", "niches branching", "morphogenesis angiogenesis", "angiogenesis bone", "remodeling and", "and wound repair.", "wound repair. redundant", "repair. redundant mechanisms", "redundant mechanisms modulate", "mechanisms modulate the", "modulate the expression", "the expression and", "expression and function", "and function of", "function of ecm", "of ecm modifying", "ecm modifying enzymes.", "modifying enzymes. abnormal", "enzymes. abnormal ecm", "abnormal ecm dynamics", "ecm dynamics can", "dynamics can lead", "can lead to", "lead to deregulated", "to deregulated cell", "deregulated cell proliferation", "cell proliferation and", "proliferation and invasion", "invasion failure", "failure of cell", "of cell death", "death and", "and loss of", "loss of cell", "differentiation resulting", "resulting in congenital", "in congenital defects", "congenital defects and", "defects and pathological", "and pathological processes", "pathological processes including", "processes including tissue", "including tissue fibrosis", "tissue fibrosis and", "fibrosis and cancer.

collagen", "and cancer.

collagen is", "cancer.

collagen is the", "is the most", "the most abundant", "most abundant fibrous", "abundant fibrous protein", "fibrous protein within", "protein within the", "within the ecm", "the ecm constituting", "ecm constituting up", "constituting up to", "up to 30%", "to 30% of", "30% of total", "of total protein", "total protein in", "protein in multicellular", "in multicellular animals.", "multicellular animals. collagen", "animals. collagen provides", "collagen provides tensile", "provides tensile strength.", "tensile strength. it", "strength. it associates", "it associates with", "associates with elastic", "with elastic fibres", "fibres composed", "composed of elastin", "of elastin and", "elastin and fibrillin", "and fibrillin microfibrils", "microfibrils which", "which give tissues", "give tissues the", "tissues the ability", "the ability to", "ability to recover", "to recover after", "recover after stretching.", "after stretching. other", "stretching. other ecm", "other ecm proteins", "ecm proteins such", "proteins such as", "such as fibronectin", "fibronectin laminins", "laminins and", "and matricellular proteins", "matricellular proteins participate", "proteins participate as", "participate as connectors", "as connectors or", "connectors or linking", "or linking proteins", "proteins daley", "daley et al.", "et al. 2008", "al. 2008 .

chondroitin", "2008 .

chondroitin sulfate", "sulfate dermatan", "dermatan sulfate and", "sulfate and keratan", "and keratan sulfate", "keratan sulfate proteoglycans", "sulfate proteoglycans are", "proteoglycans are structural", "are structural components", "structural components associated", "components associated with", "associated with collagen", "with collagen fibrils", "fibrils scott", "scott & haigh", "& haigh 1985", "1985 scott", "scott & orford", "& orford 1981", "serving to tether", "to tether the", "tether the fibril", "the fibril to", "fibril to the", "to the surrounding", "the surrounding matrix.", "surrounding matrix. decorin", "matrix. decorin belongs", "decorin belongs to", "belongs to the", "to the small", "the small leucine", "small leucine rich", "leucine rich repeat", "rich repeat proteoglycan", "repeat proteoglycan family", "family slrps", "slrps which", "which also includes", "also includes biglycan", "biglycan fibromodulin", "fibromodulin lumican", "lumican and asporin.", "and asporin. all", "asporin. all appear", "all appear to", "appear to be", "to be involved", "be involved in", "involved in collagen", "in collagen fibril", "collagen fibril formation", "fibril formation and", "formation and matrix", "and matrix assembly", "assembly ameye", "ameye & young", "& young 2002", "young 2002 .", "2002 .

ecm", ".

ecm proteins", "

ecm proteins such", "such as osteonectin", "osteonectin sparc", "osteopontin and thrombospondins", "thrombospondins 1", "and 2", "2 collectively", "collectively referred to", "referred to as", "to as matricellular", "as matricellular proteins", "proteins reviewed", "reviewed in mosher", "in mosher &", "mosher & adams", "& adams 2012", "2012 appear", "appear to modulate", "to modulate cell", "modulate cell matrix", "cell matrix interactions.", "matrix interactions. in", "interactions. in general", "in general they", "general they induce", "they induce de", "induce de adhesion", "adhesion characterized", "characterized by disruption", "by disruption of", "disruption of focal", "of focal adhesions", "focal adhesions and", "adhesions and a", "and a reorganization", "a reorganization of", "reorganization of actin", "of actin stress", "actin stress fibers", "fibers bornstein", "bornstein 2009 .", ". thrombospondin", "thrombospondin ts", "ts 1", "2 bind mmp2.", "bind mmp2. the", "mmp2. the resulting", "the resulting complex", "resulting complex is", "complex is endocytosed", "is endocytosed by", "endocytosed by the", "by the low", "the low density", "low density lipoprotein", "density lipoprotein receptor", "lipoprotein receptor related", "receptor related protein", "protein lrp", "clearing mmp2 from", "mmp2 from the", "from the ecm", "ecm yang", "yang et al.", "et al. 2001", "al. 2001 .

osteopontin", ".

osteopontin spp1", "spp1 bone", "bone sialoprotein 1", "1 interacts", "interacts with collagen", "with collagen and", "collagen and fibronectin", "fibronectin mukherjee", "mukherjee et al.", "et al. 1995", "al. 1995 .", "1995 . it", ". it also", "it also contains", "also contains several", "contains several cell", "several cell adhesive", "cell adhesive domains", "adhesive domains that", "domains that interact", "that interact with", "interact with integrins", "with integrins and", "integrins and cd44.

aggrecan", "and cd44.

aggrecan is", "cd44.

aggrecan is the", "is the predominant", "the predominant ecm", "predominant ecm proteoglycan", "ecm proteoglycan in", "proteoglycan in cartilage", "cartilage hardingham", "hardingham & fosang", "& fosang 1992", "fosang 1992 .", "1992 . its", ". its relatives", "its relatives include", "relatives include versican", "versican neurocan", "neurocan and brevican", "brevican iozzo", "iozzo 1998 .", "1998 . in", ". in articular", "in articular cartilage", "articular cartilage the", "cartilage the major", "the major non", "major non fibrous", "non fibrous macromolecules", "fibrous macromolecules are", "macromolecules are aggrecan", "aggrecan hyaluronan", "hyaluronan and hyaluronan", "and hyaluronan and", "hyaluronan and proteoglycan", "and proteoglycan link", "proteoglycan link protein", "link protein 1", "1 hapln1", "hapln1 . the", ". the high", "the high negative", "high negative charge", "negative charge density", "charge density of", "density of these", "of these molecules", "these molecules leads", "molecules leads to", "leads to the", "to the binding", "the binding of", "binding of large", "of large amounts", "large amounts of", "amounts of water", "water bruckner", "bruckner 2006 .", "2006 . hyaluronan", ". hyaluronan is", "hyaluronan is bound", "is bound by", "bound by several", "by several large", "several large proteoglycans", "large proteoglycans proteoglycans", "proteoglycans proteoglycans belonging", "proteoglycans belonging to", "belonging to the", "to the hyalectan", "the hyalectan family", "hyalectan family that", "family that form", "that form high", "form high molecular", "high molecular weight", "molecular weight aggregates", "aggregates roughley", "accounting for the", "for the turgid", "the turgid nature", "turgid nature of", "of cartilage.", "cartilage.

the most", "

the most significant", "most significant enzymes", "significant enzymes in", "enzymes in ecm", "in ecm remodeling", "ecm remodeling are", "remodeling are the", "are the matrix", "the matrix metalloproteinase", "metalloproteinase mmp", "mmp and", "and a disintegrin", "a disintegrin and", "disintegrin and metalloproteinase", "and metalloproteinase with", "metalloproteinase with thrombospondin", "with thrombospondin motifs", "motifs adamts", "adamts families", "families cawston", "cawston & young", "& young 2010", "young 2010 .", "2010 . other", ". other notable", "other notable ecm", "notable ecm degrading", "ecm degrading enzymes", "degrading enzymes include", "enzymes include plasmin", "include plasmin and", "plasmin and cathepsin", "and cathepsin g.", "cathepsin g. many", "g. many ecm", "many ecm proteinases", "ecm proteinases are", "proteinases are initially", "are initially present", "initially present as", "present as precursors", "precursors activated", "activated by proteolytic", "by proteolytic processing.", "proteolytic processing. mmp", "processing. mmp precursors", "mmp precursors include", "precursors include an", "include an amino", "an amino prodomain", "amino prodomain which", "prodomain which masks", "which masks the", "masks the catalytic", "the catalytic zn", "catalytic zn binding", "zn binding motif", "motif page", "page mccawet al.", "mccawet al. 2007", "al. 2007 .", "2007 . this", ". this can", "this can be", "can be removed", "be removed by", "removed by other", "by other proteinases", "proteinases often", "often other mmps.", "other mmps. ecm", "mmps. ecm proteinases", "ecm proteinases can", "proteinases can be", "can be inactivated", "be inactivated by", "inactivated by degradation", "degradation or", "or blocked by", "blocked by inhibitors.", "by inhibitors. some", "inhibitors. some of", "some of these", "of these inhibitors", "inhibitors including", "including alpha2 macroglobulin", "macroglobulin alpha1", "alpha1 proteinase inhibitor", "inhibitor and", "and alpha1 chymotrypsin", "alpha1 chymotrypsin can", "chymotrypsin can inhibit", "can inhibit a", "inhibit a large", "a large variety", "large variety of", "variety of proteinases", "proteinases woessner", "woessner & nagase", "& nagase 2000", "nagase 2000 .", "2000 . the", ". the tissue", "the tissue inhibitors", "tissue inhibitors of", "inhibitors of metalloproteinases", "metalloproteinases timps", "timps are", "are potent mmp", "potent mmp inhibitors", "inhibitors brew", "brew & nagase", "& nagase 2010", "nagase 2010 .", "the extracellular matrix is", "extracellular matrix is a", "matrix is a component", "is a component of", "a component of all", "component of all mammalian", "of all mammalian tissues", "mammalian tissues a", "tissues a network", "a network consisting largely", "network consisting largely of", "consisting largely of the", "largely of the fibrous", "of the fibrous proteins", "the fibrous proteins collagen", "proteins collagen elastin", "collagen elastin and", "elastin and associated microfibrils", "associated microfibrils fibronectin", "microfibrils fibronectin and", "fibronectin and laminins embedded", "and laminins embedded in", "laminins embedded in a", "embedded in a viscoelastic", "in a viscoelastic gel", "a viscoelastic gel of", "viscoelastic gel of anionic", "gel of anionic proteoglycan", "of anionic proteoglycan polymers.", "anionic proteoglycan polymers. it", "proteoglycan polymers. it performs", "polymers. it performs many", "it performs many functions", "performs many functions in", "many functions in addition", "functions in addition to", "in addition to its", "addition to its structural", "to its structural role", "structural role as", "role as a", "as a major component", "a major component of", "major component of the", "component of the cellular", "of the cellular microenvironment", "the cellular microenvironment it", "cellular microenvironment it influences", "microenvironment it influences cell", "it influences cell behaviours", "influences cell behaviours such", "cell behaviours such as", "behaviours such as proliferation", "as proliferation adhesion", "proliferation adhesion and", "and migration and", "migration and regulates", "and regulates cell differentiation", "regulates cell differentiation and", "cell differentiation and death", "and death hynes", "death hynes 2009", "hynes 2009 .

ecm", "2009 .

ecm composition", ".

ecm composition is", "

ecm composition is highly", "composition is highly heterogeneous", "is highly heterogeneous and", "highly heterogeneous and dynamic", "and dynamic being", "dynamic being constantly", "constantly remodeled frantz", "remodeled frantz et", "frantz et al. 2010", "al. 2010 and", "2010 and modulated", "and modulated largely", "modulated largely by", "largely by matrix metalloproteinases", "matrix metalloproteinases mmps", "mmps and growth", "and growth factors that", "growth factors that bind", "factors that bind to", "that bind to the", "bind to the ecm", "to the ecm influencing", "the ecm influencing the", "ecm influencing the synthesis", "the synthesis crosslinking", "synthesis crosslinking and", "crosslinking and degradation of", "and degradation of ecm", "degradation of ecm components", "ecm components hynes", "components hynes 2009", "hynes 2009 . ecm", "2009 . ecm remodeling", ". ecm remodeling is", "ecm remodeling is involved", "remodeling is involved in", "is involved in the", "involved in the regulation", "in the regulation of", "the regulation of cell", "regulation of cell differentiation", "of cell differentiation processes", "cell differentiation processes such", "differentiation processes such as", "processes such as the", "such as the establishment", "as the establishment and", "the establishment and maintenance", "establishment and maintenance of", "and maintenance of stem", "maintenance of stem cell", "of stem cell niches", "cell niches branching", "niches branching morphogenesis", "branching morphogenesis angiogenesis", "angiogenesis bone remodeling", "bone remodeling and", "remodeling and wound", "and wound repair. redundant", "wound repair. redundant mechanisms", "repair. redundant mechanisms modulate", "redundant mechanisms modulate the", "mechanisms modulate the expression", "modulate the expression and", "the expression and function", "expression and function of", "and function of ecm", "function of ecm modifying", "of ecm modifying enzymes.", "ecm modifying enzymes. abnormal", "modifying enzymes. abnormal ecm", "enzymes. abnormal ecm dynamics", "abnormal ecm dynamics can", "ecm dynamics can lead", "dynamics can lead to", "can lead to deregulated", "lead to deregulated cell", "to deregulated cell proliferation", "deregulated cell proliferation and", "cell proliferation and invasion", "and invasion failure", "invasion failure of", "failure of cell death", "cell death and", "death and loss", "and loss of cell", "loss of cell differentiation", "cell differentiation resulting", "differentiation resulting in", "resulting in congenital defects", "in congenital defects and", "congenital defects and pathological", "defects and pathological processes", "and pathological processes including", "pathological processes including tissue", "processes including tissue fibrosis", "including tissue fibrosis and", "tissue fibrosis and cancer.

collagen", "fibrosis and cancer.

collagen is", "and cancer.

collagen is the", "cancer.

collagen is the most", "is the most abundant", "the most abundant fibrous", "most abundant fibrous protein", "abundant fibrous protein within", "fibrous protein within the", "protein within the ecm", "within the ecm constituting", "the ecm constituting up", "ecm constituting up to", "constituting up to 30%", "up to 30% of", "to 30% of total", "30% of total protein", "of total protein in", "total protein in multicellular", "protein in multicellular animals.", "in multicellular animals. collagen", "multicellular animals. collagen provides", "animals. collagen provides tensile", "collagen provides tensile strength.", "provides tensile strength. it", "tensile strength. it associates", "strength. it associates with", "it associates with elastic", "associates with elastic fibres", "elastic fibres composed", "fibres composed of", "composed of elastin and", "of elastin and fibrillin", "elastin and fibrillin microfibrils", "fibrillin microfibrils which", "microfibrils which give", "which give tissues the", "give tissues the ability", "tissues the ability to", "the ability to recover", "ability to recover after", "to recover after stretching.", "recover after stretching. other", "after stretching. other ecm", "stretching. other ecm proteins", "other ecm proteins such", "ecm proteins such as", "proteins such as fibronectin", "as fibronectin laminins", "laminins and matricellular", "and matricellular proteins participate", "matricellular proteins participate as", "proteins participate as connectors", "participate as connectors or", "as connectors or linking", "connectors or linking proteins", "linking proteins daley", "proteins daley et", "daley et al. 2008", "et al. 2008 .

chondroitin", "al. 2008 .

chondroitin sulfate", ".

chondroitin sulfate dermatan", "sulfate dermatan sulfate", "dermatan sulfate and keratan", "sulfate and keratan sulfate", "and keratan sulfate proteoglycans", "keratan sulfate proteoglycans are", "sulfate proteoglycans are structural", "proteoglycans are structural components", "are structural components associated", "structural components associated with", "components associated with collagen", "associated with collagen fibrils", "collagen fibrils scott", "fibrils scott &", "scott & haigh 1985", "haigh 1985 scott", "1985 scott &", "scott & orford 1981", "1981 serving", "serving to tether the", "to tether the fibril", "tether the fibril to", "the fibril to the", "fibril to the surrounding", "to the surrounding matrix.", "the surrounding matrix. decorin", "surrounding matrix. decorin belongs", "matrix. decorin belongs to", "decorin belongs to the", "belongs to the small", "to the small leucine", "the small leucine rich", "small leucine rich repeat", "leucine rich repeat proteoglycan", "rich repeat proteoglycan family", "proteoglycan family slrps", "slrps which also", "which also includes biglycan", "includes biglycan fibromodulin", "fibromodulin lumican and", "lumican and asporin. all", "and asporin. all appear", "asporin. all appear to", "all appear to be", "appear to be involved", "to be involved in", "be involved in collagen", "involved in collagen fibril", "in collagen fibril formation", "collagen fibril formation and", "fibril formation and matrix", "formation and matrix assembly", "matrix assembly ameye", "assembly ameye &", "ameye & young 2002", "& young 2002 .", "young 2002 .

ecm", "2002 .

ecm proteins", ".

ecm proteins such", "

ecm proteins such as", "proteins such as osteonectin", "as osteonectin sparc", "sparc osteopontin", "and thrombospondins 1", "thrombospondins 1 and", "1 and 2", "2 collectively referred", "collectively referred to as", "referred to as matricellular", "to as matricellular proteins", "matricellular proteins reviewed", "proteins reviewed in", "reviewed in mosher &", "in mosher & adams", "mosher & adams 2012", "adams 2012 appear", "2012 appear to", "appear to modulate cell", "to modulate cell matrix", "modulate cell matrix interactions.", "cell matrix interactions. in", "matrix interactions. in general", "interactions. in general they", "in general they induce", "general they induce de", "they induce de adhesion", "de adhesion characterized", "adhesion characterized by", "characterized by disruption of", "by disruption of focal", "disruption of focal adhesions", "of focal adhesions and", "focal adhesions and a", "adhesions and a reorganization", "and a reorganization of", "a reorganization of actin", "reorganization of actin stress", "of actin stress fibers", "stress fibers bornstein", "fibers bornstein 2009", "2009 . thrombospondin", "ts 1 and", "and 2 bind", "2 bind mmp2. the", "bind mmp2. the resulting", "mmp2. the resulting complex", "the resulting complex is", "resulting complex is endocytosed", "complex is endocytosed by", "is endocytosed by the", "endocytosed by the low", "by the low density", "the low density lipoprotein", "low density lipoprotein receptor", "density lipoprotein receptor related", "lipoprotein receptor related protein", "related protein lrp", "lrp clearing", "clearing mmp2 from the", "mmp2 from the ecm", "the ecm yang", "ecm yang et", "yang et al. 2001", "et al. 2001 .

osteopontin", "2001 .

osteopontin spp1", "spp1 bone sialoprotein", "sialoprotein 1 interacts", "1 interacts with", "interacts with collagen and", "with collagen and fibronectin", "and fibronectin mukherjee", "fibronectin mukherjee et", "mukherjee et al. 1995", "et al. 1995 .", "al. 1995 . it", "1995 . it also", ". it also contains", "it also contains several", "also contains several cell", "contains several cell adhesive", "several cell adhesive domains", "cell adhesive domains that", "adhesive domains that interact", "domains that interact with", "that interact with integrins", "interact with integrins and", "with integrins and cd44.

aggrecan", "integrins and cd44.

aggrecan is", "and cd44.

aggrecan is the", "cd44.

aggrecan is the predominant", "is the predominant ecm", "the predominant ecm proteoglycan", "predominant ecm proteoglycan in", "ecm proteoglycan in cartilage", "in cartilage hardingham", "cartilage hardingham &", "hardingham & fosang 1992", "& fosang 1992 .", "fosang 1992 . its", "1992 . its relatives", ". its relatives include", "its relatives include versican", "include versican neurocan", "versican neurocan and", "and brevican iozzo", "brevican iozzo 1998", "iozzo 1998 . in", "1998 . in articular", ". in articular cartilage", "in articular cartilage the", "articular cartilage the major", "cartilage the major non", "the major non fibrous", "major non fibrous macromolecules", "non fibrous macromolecules are", "fibrous macromolecules are aggrecan", "are aggrecan hyaluronan", "aggrecan hyaluronan and", "hyaluronan and hyaluronan and", "and hyaluronan and proteoglycan", "hyaluronan and proteoglycan link", "and proteoglycan link protein", "proteoglycan link protein 1", "protein 1 hapln1", "1 hapln1 .", "hapln1 . the high", ". the high negative", "the high negative charge", "high negative charge density", "negative charge density of", "charge density of these", "density of these molecules", "of these molecules leads", "these molecules leads to", "molecules leads to the", "leads to the binding", "to the binding of", "the binding of large", "binding of large amounts", "of large amounts of", "large amounts of water", "of water bruckner", "water bruckner 2006", "bruckner 2006 . hyaluronan", "2006 . hyaluronan is", ". hyaluronan is bound", "hyaluronan is bound by", "is bound by several", "bound by several large", "by several large proteoglycans", "several large proteoglycans proteoglycans", "large proteoglycans proteoglycans belonging", "proteoglycans proteoglycans belonging to", "proteoglycans belonging to the", "belonging to the hyalectan", "to the hyalectan family", "the hyalectan family that", "hyalectan family that form", "family that form high", "that form high molecular", "form high molecular weight", "high molecular weight aggregates", "weight aggregates roughley", "aggregates roughley 2006", "2006 accounting", "accounting for the turgid", "for the turgid nature", "the turgid nature of", "nature of cartilage.", "of cartilage.

the", "cartilage.

the most significant", "

the most significant enzymes", "most significant enzymes in", "significant enzymes in ecm", "enzymes in ecm remodeling", "in ecm remodeling are", "ecm remodeling are the", "remodeling are the matrix", "are the matrix metalloproteinase", "matrix metalloproteinase mmp", "mmp and a", "and a disintegrin and", "a disintegrin and metalloproteinase", "disintegrin and metalloproteinase with", "and metalloproteinase with thrombospondin", "metalloproteinase with thrombospondin motifs", "thrombospondin motifs adamts", "families cawston &", "cawston & young 2010", "& young 2010 .", "young 2010 . other", "2010 . other notable", ". other notable ecm", "other notable ecm degrading", "notable ecm degrading enzymes", "ecm degrading enzymes include", "degrading enzymes include plasmin", "enzymes include plasmin and", "include plasmin and cathepsin", "plasmin and cathepsin g.", "and cathepsin g. many", "cathepsin g. many ecm", "g. many ecm proteinases", "many ecm proteinases are", "ecm proteinases are initially", "proteinases are initially present", "are initially present as", "initially present as precursors", "as precursors activated", "precursors activated by", "activated by proteolytic processing.", "by proteolytic processing. mmp", "proteolytic processing. mmp precursors", "processing. mmp precursors include", "mmp precursors include an", "precursors include an amino", "include an amino prodomain", "an amino prodomain which", "amino prodomain which masks", "prodomain which masks the", "which masks the catalytic", "masks the catalytic zn", "the catalytic zn binding", "catalytic zn binding motif", "binding motif page", "motif page mccawet", "page mccawet al. 2007", "mccawet al. 2007 .", "al. 2007 . this", "2007 . this can", ". this can be", "this can be removed", "can be removed by", "be removed by other", "removed by other proteinases", "other proteinases often", "proteinases often other", "often other mmps. ecm", "other mmps. ecm proteinases", "mmps. ecm proteinases can", "ecm proteinases can be", "proteinases can be inactivated", "can be inactivated by", "be inactivated by degradation", "by degradation or", "degradation or blocked", "or blocked by inhibitors.", "blocked by inhibitors. some", "by inhibitors. some of", "inhibitors. some of these", "some of these inhibitors", "these inhibitors including", "inhibitors including alpha2", "alpha2 macroglobulin alpha1", "macroglobulin alpha1 proteinase", "proteinase inhibitor and", "inhibitor and alpha1", "and alpha1 chymotrypsin can", "alpha1 chymotrypsin can inhibit", "chymotrypsin can inhibit a", "can inhibit a large", "inhibit a large variety", "a large variety of", "large variety of proteinases", "of proteinases woessner", "proteinases woessner &", "woessner & nagase 2000", "& nagase 2000 .", "nagase 2000 . the", "2000 . the tissue", ". the tissue inhibitors", "the tissue inhibitors of", "tissue inhibitors of metalloproteinases", "of metalloproteinases timps", "timps are potent", "are potent mmp inhibitors", "mmp inhibitors brew", "inhibitors brew &", "brew & nagase 2010", "& nagase 2010 .", "the extracellular matrix is a", "extracellular matrix is a component", "matrix is a component of", "is a component of all", "a component of all mammalian", "component of all mammalian tissues", "all mammalian tissues a", "mammalian tissues a network", "tissues a network consisting", "a network consisting largely of", "network consisting largely of the", "consisting largely of the fibrous", "largely of the fibrous proteins", "of the fibrous proteins collagen", "fibrous proteins collagen elastin", "proteins collagen elastin and", "collagen elastin and associated", "and associated microfibrils fibronectin", "associated microfibrils fibronectin and", "microfibrils fibronectin and laminins", "fibronectin and laminins embedded in", "and laminins embedded in a", "laminins embedded in a viscoelastic", "embedded in a viscoelastic gel", "in a viscoelastic gel of", "a viscoelastic gel of anionic", "viscoelastic gel of anionic proteoglycan", "gel of anionic proteoglycan polymers.", "of anionic proteoglycan polymers. it", "anionic proteoglycan polymers. it performs", "proteoglycan polymers. it performs many", "polymers. it performs many functions", "it performs many functions in", "performs many functions in addition", "many functions in addition to", "functions in addition to its", "in addition to its structural", "addition to its structural role", "its structural role as", "structural role as a", "role as a major", "as a major component of", "a major component of the", "major component of the cellular", "component of the cellular microenvironment", "of the cellular microenvironment it", "the cellular microenvironment it influences", "cellular microenvironment it influences cell", "microenvironment it influences cell behaviours", "it influences cell behaviours such", "influences cell behaviours such as", "cell behaviours such as proliferation", "such as proliferation adhesion", "as proliferation adhesion and", "proliferation adhesion and migration", "adhesion and migration and", "and migration and regulates", "migration and regulates cell", "and regulates cell differentiation and", "regulates cell differentiation and death", "differentiation and death hynes", "and death hynes 2009", "death hynes 2009 .", "hynes 2009 .

ecm composition", "2009 .

ecm composition is", ".

ecm composition is highly", "

ecm composition is highly heterogeneous", "composition is highly heterogeneous and", "is highly heterogeneous and dynamic", "heterogeneous and dynamic being", "and dynamic being constantly", "dynamic being constantly remodeled", "being constantly remodeled frantz", "constantly remodeled frantz et", "remodeled frantz et al.", "et al. 2010 and", "al. 2010 and modulated", "and modulated largely by", "modulated largely by matrix", "by matrix metalloproteinases mmps", "metalloproteinases mmps and", "mmps and growth factors", "and growth factors that bind", "growth factors that bind to", "factors that bind to the", "that bind to the ecm", "bind to the ecm influencing", "to the ecm influencing the", "the ecm influencing the synthesis", "influencing the synthesis crosslinking", "the synthesis crosslinking and", "synthesis crosslinking and degradation", "crosslinking and degradation of ecm", "and degradation of ecm components", "of ecm components hynes", "ecm components hynes 2009", "components hynes 2009 .", "hynes 2009 . ecm remodeling", "2009 . ecm remodeling is", ". ecm remodeling is involved", "ecm remodeling is involved in", "remodeling is involved in the", "is involved in the regulation", "involved in the regulation of", "in the regulation of cell", "the regulation of cell differentiation", "regulation of cell differentiation processes", "of cell differentiation processes such", "cell differentiation processes such as", "differentiation processes such as the", "processes such as the establishment", "such as the establishment and", "as the establishment and maintenance", "the establishment and maintenance of", "establishment and maintenance of stem", "and maintenance of stem cell", "maintenance of stem cell niches", "stem cell niches branching", "cell niches branching morphogenesis", "morphogenesis angiogenesis bone", "bone remodeling and wound", "remodeling and wound repair.", "and wound repair. redundant mechanisms", "wound repair. redundant mechanisms modulate", "repair. redundant mechanisms modulate the", "redundant mechanisms modulate the expression", "mechanisms modulate the expression and", "modulate the expression and function", "the expression and function of", "expression and function of ecm", "and function of ecm modifying", "function of ecm modifying enzymes.", "of ecm modifying enzymes. abnormal", "ecm modifying enzymes. abnormal ecm", "modifying enzymes. abnormal ecm dynamics", "enzymes. abnormal ecm dynamics can", "abnormal ecm dynamics can lead", "ecm dynamics can lead to", "dynamics can lead to deregulated", "can lead to deregulated cell", "lead to deregulated cell proliferation", "to deregulated cell proliferation and", "deregulated cell proliferation and invasion", "proliferation and invasion failure", "and invasion failure of", "invasion failure of cell", "of cell death and", "cell death and loss", "death and loss of", "and loss of cell differentiation", "of cell differentiation resulting", "cell differentiation resulting in", "differentiation resulting in congenital", "resulting in congenital defects and", "in congenital defects and pathological", "congenital defects and pathological processes", "defects and pathological processes including", "and pathological processes including tissue", "pathological processes including tissue fibrosis", "processes including tissue fibrosis and", "including tissue fibrosis and cancer.

collagen", "tissue fibrosis and cancer.

collagen is", "fibrosis and cancer.

collagen is the", "and cancer.

collagen is the most", "cancer.

collagen is the most abundant", "is the most abundant fibrous", "the most abundant fibrous protein", "most abundant fibrous protein within", "abundant fibrous protein within the", "fibrous protein within the ecm", "protein within the ecm constituting", "within the ecm constituting up", "the ecm constituting up to", "ecm constituting up to 30%", "constituting up to 30% of", "up to 30% of total", "to 30% of total protein", "30% of total protein in", "of total protein in multicellular", "total protein in multicellular animals.", "protein in multicellular animals. collagen", "in multicellular animals. collagen provides", "multicellular animals. collagen provides tensile", "animals. collagen provides tensile strength.", "collagen provides tensile strength. it", "provides tensile strength. it associates", "tensile strength. it associates with", "strength. it associates with elastic", "it associates with elastic fibres", "with elastic fibres composed", "elastic fibres composed of", "fibres composed of elastin", "composed of elastin and fibrillin", "of elastin and fibrillin microfibrils", "and fibrillin microfibrils which", "fibrillin microfibrils which give", "microfibrils which give tissues", "which give tissues the ability", "give tissues the ability to", "tissues the ability to recover", "the ability to recover after", "ability to recover after stretching.", "to recover after stretching. other", "recover after stretching. other ecm", "after stretching. other ecm proteins", "stretching. other ecm proteins such", "other ecm proteins such as", "ecm proteins such as fibronectin", "such as fibronectin laminins", "fibronectin laminins and", "laminins and matricellular proteins", "and matricellular proteins participate as", "matricellular proteins participate as connectors", "proteins participate as connectors or", "participate as connectors or linking", "as connectors or linking proteins", "or linking proteins daley", "linking proteins daley et", "proteins daley et al.", "daley et al. 2008 .

chondroitin", "et al. 2008 .

chondroitin sulfate", "2008 .

chondroitin sulfate dermatan", ".

chondroitin sulfate dermatan sulfate", "sulfate dermatan sulfate and", "dermatan sulfate and keratan sulfate", "sulfate and keratan sulfate proteoglycans", "and keratan sulfate proteoglycans are", "keratan sulfate proteoglycans are structural", "sulfate proteoglycans are structural components", "proteoglycans are structural components associated", "are structural components associated with", "structural components associated with collagen", "components associated with collagen fibrils", "with collagen fibrils scott", "collagen fibrils scott &", "fibrils scott & haigh", "& haigh 1985 scott", "haigh 1985 scott &", "1985 scott & orford", "orford 1981 serving", "1981 serving to", "serving to tether the fibril", "to tether the fibril to", "tether the fibril to the", "the fibril to the surrounding", "fibril to the surrounding matrix.", "to the surrounding matrix. decorin", "the surrounding matrix. decorin belongs", "surrounding matrix. decorin belongs to", "matrix. decorin belongs to the", "decorin belongs to the small", "belongs to the small leucine", "to the small leucine rich", "the small leucine rich repeat", "small leucine rich repeat proteoglycan", "leucine rich repeat proteoglycan family", "repeat proteoglycan family slrps", "family slrps which", "slrps which also includes", "also includes biglycan fibromodulin", "biglycan fibromodulin lumican", "fibromodulin lumican and asporin.", "lumican and asporin. all appear", "and asporin. all appear to", "asporin. all appear to be", "all appear to be involved", "appear to be involved in", "to be involved in collagen", "be involved in collagen fibril", "involved in collagen fibril formation", "in collagen fibril formation and", "collagen fibril formation and matrix", "fibril formation and matrix assembly", "and matrix assembly ameye", "matrix assembly ameye &", "assembly ameye & young", "ameye & young 2002 .", "& young 2002 .

ecm", "young 2002 .

ecm proteins", "2002 .

ecm proteins such", ".

ecm proteins such as", "

ecm proteins such as osteonectin", "such as osteonectin sparc", "sparc osteopontin and", "osteopontin and thrombospondins 1", "and thrombospondins 1 and", "and 2 collectively", "2 collectively referred to", "collectively referred to as matricellular", "referred to as matricellular proteins", "as matricellular proteins reviewed", "matricellular proteins reviewed in", "proteins reviewed in mosher", "reviewed in mosher & adams", "in mosher & adams 2012", "& adams 2012 appear", "adams 2012 appear to", "2012 appear to modulate", "appear to modulate cell matrix", "to modulate cell matrix interactions.", "modulate cell matrix interactions. in", "cell matrix interactions. in general", "matrix interactions. in general they", "interactions. in general they induce", "in general they induce de", "general they induce de adhesion", "induce de adhesion characterized", "de adhesion characterized by", "adhesion characterized by disruption", "characterized by disruption of focal", "by disruption of focal adhesions", "disruption of focal adhesions and", "of focal adhesions and a", "focal adhesions and a reorganization", "adhesions and a reorganization of", "and a reorganization of actin", "a reorganization of actin stress", "reorganization of actin stress fibers", "actin stress fibers bornstein", "stress fibers bornstein 2009", "fibers bornstein 2009 .", "bornstein 2009 . thrombospondin", ". thrombospondin ts", "thrombospondin ts 1", "1 and 2 bind", "and 2 bind mmp2.", "2 bind mmp2. the resulting", "bind mmp2. the resulting complex", "mmp2. the resulting complex is", "the resulting complex is endocytosed", "resulting complex is endocytosed by", "complex is endocytosed by the", "is endocytosed by the low", "endocytosed by the low density", "by the low density lipoprotein", "the low density lipoprotein receptor", "low density lipoprotein receptor related", "density lipoprotein receptor related protein", "receptor related protein lrp", "lrp clearing mmp2", "clearing mmp2 from the ecm", "from the ecm yang", "the ecm yang et", "ecm yang et al.", "yang et al. 2001 .

osteopontin", "al. 2001 .

osteopontin spp1", ".

osteopontin spp1 bone", "spp1 bone sialoprotein 1", "bone sialoprotein 1 interacts", "sialoprotein 1 interacts with", "1 interacts with collagen", "interacts with collagen and fibronectin", "collagen and fibronectin mukherjee", "and fibronectin mukherjee et", "fibronectin mukherjee et al.", "mukherjee et al. 1995 .", "et al. 1995 . it", "al. 1995 . it also", "1995 . it also contains", ". it also contains several", "it also contains several cell", "also contains several cell adhesive", "contains several cell adhesive domains", "several cell adhesive domains that", "cell adhesive domains that interact", "adhesive domains that interact with", "domains that interact with integrins", "that interact with integrins and", "interact with integrins and cd44.

aggrecan", "with integrins and cd44.

aggrecan is", "integrins and cd44.

aggrecan is the", "and cd44.

aggrecan is the predominant", "cd44.

aggrecan is the predominant ecm", "is the predominant ecm proteoglycan", "the predominant ecm proteoglycan in", "predominant ecm proteoglycan in cartilage", "proteoglycan in cartilage hardingham", "in cartilage hardingham &", "cartilage hardingham & fosang", "hardingham & fosang 1992 .", "& fosang 1992 . its", "fosang 1992 . its relatives", "1992 . its relatives include", ". its relatives include versican", "relatives include versican neurocan", "include versican neurocan and", "versican neurocan and brevican", "neurocan and brevican iozzo", "and brevican iozzo 1998", "brevican iozzo 1998 .", "iozzo 1998 . in articular", "1998 . in articular cartilage", ". in articular cartilage the", "in articular cartilage the major", "articular cartilage the major non", "cartilage the major non fibrous", "the major non fibrous macromolecules", "major non fibrous macromolecules are", "non fibrous macromolecules are aggrecan", "macromolecules are aggrecan hyaluronan", "are aggrecan hyaluronan and", "aggrecan hyaluronan and hyaluronan", "hyaluronan and hyaluronan and proteoglycan", "and hyaluronan and proteoglycan link", "hyaluronan and proteoglycan link protein", "and proteoglycan link protein 1", "link protein 1 hapln1", "protein 1 hapln1 .", "1 hapln1 . the", "hapln1 . the high negative", ". the high negative charge", "the high negative charge density", "high negative charge density of", "negative charge density of these", "charge density of these molecules", "density of these molecules leads", "of these molecules leads to", "these molecules leads to the", "molecules leads to the binding", "leads to the binding of", "to the binding of large", "the binding of large amounts", "binding of large amounts of", "of large amounts of water", "amounts of water bruckner", "of water bruckner 2006", "water bruckner 2006 .", "bruckner 2006 . hyaluronan is", "2006 . hyaluronan is bound", ". hyaluronan is bound by", "hyaluronan is bound by several", "is bound by several large", "bound by several large proteoglycans", "by several large proteoglycans proteoglycans", "several large proteoglycans proteoglycans belonging", "large proteoglycans proteoglycans belonging to", "proteoglycans proteoglycans belonging to the", "proteoglycans belonging to the hyalectan", "belonging to the hyalectan family", "to the hyalectan family that", "the hyalectan family that form", "hyalectan family that form high", "family that form high molecular", "that form high molecular weight", "form high molecular weight aggregates", "molecular weight aggregates roughley", "weight aggregates roughley 2006", "roughley 2006 accounting", "2006 accounting for", "accounting for the turgid nature", "for the turgid nature of", "turgid nature of cartilage.", "nature of cartilage.

the", "of cartilage.

the most", "cartilage.

the most significant enzymes", "

the most significant enzymes in", "most significant enzymes in ecm", "significant enzymes in ecm remodeling", "enzymes in ecm remodeling are", "in ecm remodeling are the", "ecm remodeling are the matrix", "remodeling are the matrix metalloproteinase", "the matrix metalloproteinase mmp", "metalloproteinase mmp and", "mmp and a disintegrin", "and a disintegrin and metalloproteinase", "a disintegrin and metalloproteinase with", "disintegrin and metalloproteinase with thrombospondin", "and metalloproteinase with thrombospondin motifs", "with thrombospondin motifs adamts", "motifs adamts families", "adamts families cawston", "families cawston & young", "cawston & young 2010 .", "& young 2010 . other", "young 2010 . other notable", "2010 . other notable ecm", ". other notable ecm degrading", "other notable ecm degrading enzymes", "notable ecm degrading enzymes include", "ecm degrading enzymes include plasmin", "degrading enzymes include plasmin and", "enzymes include plasmin and cathepsin", "include plasmin and cathepsin g.", "plasmin and cathepsin g. many", "and cathepsin g. many ecm", "cathepsin g. many ecm proteinases", "g. many ecm proteinases are", "many ecm proteinases are initially", "ecm proteinases are initially present", "proteinases are initially present as", "are initially present as precursors", "present as precursors activated", "as precursors activated by", "precursors activated by proteolytic", "activated by proteolytic processing. mmp", "by proteolytic processing. mmp precursors", "proteolytic processing. mmp precursors include", "processing. mmp precursors include an", "mmp precursors include an amino", "precursors include an amino prodomain", "include an amino prodomain which", "an amino prodomain which masks", "amino prodomain which masks the", "prodomain which masks the catalytic", "which masks the catalytic zn", "masks the catalytic zn binding", "the catalytic zn binding motif", "zn binding motif page", "binding motif page mccawet", "motif page mccawet al.", "page mccawet al. 2007 .", "mccawet al. 2007 . this", "al. 2007 . this can", "2007 . this can be", ". this can be removed", "this can be removed by", "can be removed by other", "be removed by other proteinases", "by other proteinases often", "other proteinases often other", "proteinases often other mmps.", "often other mmps. ecm proteinases", "other mmps. ecm proteinases can", "mmps. ecm proteinases can be", "ecm proteinases can be inactivated", "proteinases can be inactivated by", "can be inactivated by degradation", "inactivated by degradation or", "by degradation or blocked", "degradation or blocked by", "or blocked by inhibitors. some", "blocked by inhibitors. some of", "by inhibitors. some of these", "inhibitors. some of these inhibitors", "of these inhibitors including", "these inhibitors including alpha2", "inhibitors including alpha2 macroglobulin", "including alpha2 macroglobulin alpha1", "alpha2 macroglobulin alpha1 proteinase", "macroglobulin alpha1 proteinase inhibitor", "alpha1 proteinase inhibitor and", "proteinase inhibitor and alpha1", "inhibitor and alpha1 chymotrypsin", "and alpha1 chymotrypsin can inhibit", "alpha1 chymotrypsin can inhibit a", "chymotrypsin can inhibit a large", "can inhibit a large variety", "inhibit a large variety of", "a large variety of proteinases", "variety of proteinases woessner", "of proteinases woessner &", "proteinases woessner & nagase", "woessner & nagase 2000 .", "& nagase 2000 . the", "nagase 2000 . the tissue", "2000 . the tissue inhibitors", ". the tissue inhibitors of", "the tissue inhibitors of metalloproteinases", "inhibitors of metalloproteinases timps", "metalloproteinases timps are", "timps are potent mmp", "potent mmp inhibitors brew", "mmp inhibitors brew &", "inhibitors brew & nagase", "brew & nagase 2010 ." ] }, { "record_id": "GLY_000594_1_767", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1475029", "r hsa", "hsa 1475029", "r hsa 1475029" ] }, { "record_id": "GLY_000594_1_767", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "reversible hydration", "hydration of", "of carbon", "carbon dioxide", "reversible hydration of", "hydration of carbon", "of carbon dioxide", "reversible hydration of carbon", "hydration of carbon dioxide", "reversible hydration of carbon dioxide", "carbonic anhydrases", "anhydrases reversibly", "reversibly catalyze", "catalyze the", "the hydration", "dioxide and", "and directly", "directly produce", "produce bicarbonate", "bicarbonate and", "and protons", "bypassing the", "the formation", "formation of", "of carbonic", "carbonic acid", "reviewed in", "in lindskog", "lindskog 1997", "breton 2001", "esbaugh and", "and tufts", "tufts 2006", "boron 2010", "gilmour 2010", "2010 .", ". carbonic", "carbonic anhydrase", "anhydrase deprotonates", "deprotonates water", "water to", "to yield", "yield a", "a zinc", "zinc hydroxyl", "hydroxyl group", "group and", 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molecule displaces the", "water molecule displaces the bicarbonate", "molecule displaces the bicarbonate and", "displaces the bicarbonate and the", "the bicarbonate and the reaction", "bicarbonate and the reaction cycle", "and the reaction cycle begins", "the reaction cycle begins again.", "reaction cycle begins again. there", "cycle begins again. there are", "begins again. there are currently", "again. there are currently 12", "there are currently 12 known", "are currently 12 known active", "currently 12 known active carbonic", "12 known active carbonic anhydrases", "known active carbonic anhydrases in", "active carbonic anhydrases in humans." ] }, { "record_id": "GLY_000594_1_768", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1482798", "r hsa", "hsa 1482798", "r hsa 1482798" ] }, { "record_id": "GLY_000594_1_768", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acyl chain", "chain remodeling", "remodeling of", "of cl", "acyl chain remodeling", "chain remodeling of", "remodeling of cl", "acyl chain remodeling of", "chain remodeling of cl", "acyl chain remodeling of cl", "of cardiolipin", "occurs in", "in the", "the inner", "inner mitochondria", "mitochondria membranes", "via hydrolysis", "hydrolysis by", "by phopholipases", "phopholipases and", "and subsequent", "subsequent reacylation", "reacylation by", "by acyltransferases.", "at the", "the endoplasmic", "endoplasmic reticulum", "membrane the", "the situation", "situation is", "is more", "more complicated", "complicated with", "with monolysocardiolipin", "involved in", "in hydrolysis", "hydrolysis and", "reacylation back", "back to", "to cl", "zachman et", "et al.", "al. 2010", "malhotra et", "al. 2009", "xu et", "al. 2003", "taylor &", "& hatch", "hatch 2009", "cao et", "al. 2004", "zhao et", "buckland et", "al. 1998", "1998 .", "remodeling of cardiolipin", "cardiolipin cl", "cl occurs", "occurs in the", "in the inner", "the inner mitochondria", "inner mitochondria membranes", "membranes im", "im via", "via hydrolysis by", "hydrolysis by phopholipases", "by phopholipases and", "phopholipases and subsequent", "and subsequent reacylation", "subsequent reacylation by", "reacylation by acyltransferases.", "acyltransferases. at", "at the endoplasmic", "the endoplasmic reticulum", "reticulum er", "er membrane", "membrane the situation", "the situation is", "situation is more", "is more complicated", "more complicated with", "complicated with monolysocardiolipin", "monolysocardiolipin mlcl", "mlcl involved", "involved in hydrolysis", "in hydrolysis and", "hydrolysis and subsequent", "subsequent reacylation back", "reacylation back to", "back to cl", "cl zachman", "zachman et al.", "et al. 2010", "2010 malhotra", "malhotra et al.", "et al. 2009", "2009 xu", "xu et al.", "et al. 2003", "2003 taylor", "taylor & hatch", "& hatch 2009", "2009 cao", "cao et al.", "et al. 2004", "2004 zhao", "zhao et al.", "2009 buckland", "buckland et al.", "et al. 1998", "al. 1998 .", "chain remodeling of cardiolipin", "of cardiolipin cl", "cl occurs in", "occurs in the inner", "in the inner mitochondria", "the inner mitochondria membranes", "mitochondria membranes im", "im via hydrolysis", "via hydrolysis by phopholipases", "hydrolysis by phopholipases and", "by phopholipases and subsequent", "phopholipases and subsequent reacylation", "and subsequent reacylation by", "subsequent reacylation by acyltransferases.", "by acyltransferases. at", "acyltransferases. at the", "at the endoplasmic reticulum", "endoplasmic reticulum er", "er membrane the", "membrane the situation is", "the situation is more", "situation is more complicated", "is more complicated with", "more complicated with monolysocardiolipin", "with monolysocardiolipin mlcl", "mlcl involved in", "involved in hydrolysis and", "in hydrolysis and subsequent", "hydrolysis and subsequent reacylation", "and subsequent reacylation back", "subsequent reacylation back to", "reacylation back to cl", "to cl zachman", "cl zachman et", "zachman et al. 2010", "al. 2010 malhotra", "2010 malhotra et", "malhotra et al. 2009", "al. 2009 xu", "2009 xu et", "xu et al. 2003", "al. 2003 taylor", "2003 taylor &", "taylor & hatch 2009", "hatch 2009 cao", "2009 cao et", "cao et al. 2004", "al. 2004 zhao", "2004 zhao et", "zhao et al. 2009", "al. 2009 buckland", "2009 buckland et", "buckland et al. 1998", "et al. 1998 .", "acyl chain remodeling of cardiolipin", "remodeling of cardiolipin cl", "cardiolipin cl occurs", "cl occurs in the", "occurs in the inner mitochondria", "in the inner mitochondria membranes", "inner mitochondria membranes im", "membranes im via", "im via hydrolysis by", "via hydrolysis by phopholipases and", "hydrolysis by phopholipases and subsequent", "by phopholipases and subsequent reacylation", "phopholipases and subsequent reacylation by", "and subsequent reacylation by acyltransferases.", "reacylation by acyltransferases. at", "by acyltransferases. at the", "acyltransferases. at the endoplasmic", "the endoplasmic reticulum er", "reticulum er membrane", "er membrane the situation", "membrane the situation is more", "the situation is more complicated", "situation is more complicated with", "is more complicated with monolysocardiolipin", "complicated with monolysocardiolipin mlcl", "monolysocardiolipin mlcl involved", "mlcl involved in hydrolysis", "involved in hydrolysis and subsequent", "in hydrolysis and subsequent reacylation", "hydrolysis and subsequent reacylation back", "and subsequent reacylation back to", "subsequent reacylation back to cl", "back to cl zachman", "to cl zachman et", "cl zachman et al.", "et al. 2010 malhotra", "al. 2010 malhotra et", "2010 malhotra et al.", "et al. 2009 xu", "al. 2009 xu et", "2009 xu et al.", "et al. 2003 taylor", "al. 2003 taylor &", "2003 taylor & hatch", "& hatch 2009 cao", "hatch 2009 cao et", "2009 cao et al.", "et al. 2004 zhao", "al. 2004 zhao et", "2004 zhao et al.", "et al. 2009 buckland", "al. 2009 buckland et", "2009 buckland et al.", "buckland et al. 1998 ." ] }, { "record_id": "GLY_000594_1_769", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1482883", "r hsa", "hsa 1482883", "r hsa 1482883" ] }, { "record_id": "GLY_000594_1_769", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acyl chain", "chain remodeling", "remodeling of", "of dag", "dag and", "and tag", "acyl chain remodeling", "chain remodeling of", "remodeling of dag", "of dag and", "dag and tag", "acyl chain remodeling of", "chain remodeling of dag", "remodeling of dag and", "of dag and tag", "acyl chain remodeling of dag", "chain remodeling of dag and", "remodeling of dag and tag", "of triacylglycerol", "and diacylglycerol", "progresses through", "through their", "their hydrolysis", "hydrolysis by", "by patatin", "patatin like", "like phospholipase", "phospholipase domain", "domain containing", "containing proteins", "proteins 2/3", "pnpla2/3 .", "dag is", "is reacylated", "reacylated back", "back to", "to tag", "tag by", "by acylglycerol", "acylglycerol o", "o acyltransferase", "acyltransferase 1/2", "while dag", "and its", "its hydrolysis", "hydrolysis product", "product 2", "2 monoacylglycerol", "2 mag", "are transacylated", "transacylated back", "by pnpla2/3.", "in addition", "the dag", "dag hydrolysis", "mag is", "is subsequently", "subsequently hydrolyzed", "hydrolyzed to", "to fatty", "fatty acid", "acid and", "and glycerol", "glycerol by", "by monoglyceride", "monoglyceride lipase", "jenkins et", "et al.", "al. 2004", "2004 .", "remodeling of triacylglycerol", "triacylglycerol tag", "tag and", "diacylglycerol dag", "dag progresses", "progresses through their", "through their hydrolysis", "their hydrolysis by", "hydrolysis by patatin", "by patatin like", "patatin like phospholipase", "like phospholipase domain", "phospholipase domain containing", "domain containing proteins", "containing proteins 2/3", "2/3 pnpla2/3", ". dag", "dag is reacylated", "is reacylated back", "reacylated back to", "back to tag", "to tag by", "tag by acylglycerol", "by acylglycerol o", "acylglycerol o acyltransferase", "o acyltransferase 1/2", "1/2 dgat1/2", "while dag and", "dag and its", "and its hydrolysis", "its hydrolysis product", "hydrolysis product 2", "product 2 monoacylglycerol", "monoacylglycerol 2", "mag are", "are transacylated back", "transacylated back to", "tag by pnpla2/3.", "pnpla2/3. in", "addition the", "the dag hydrolysis", "dag hydrolysis product", "product 2 mag", "2 mag is", "mag is subsequently", "is subsequently hydrolyzed", "subsequently hydrolyzed to", "hydrolyzed to fatty", "to fatty acid", "fatty acid and", "acid and glycerol", "and glycerol by", "glycerol by monoglyceride", "by monoglyceride lipase", "lipase mgll", "jenkins et al.", "et al. 2004", "al. 2004 .", "chain remodeling of triacylglycerol", "of triacylglycerol tag", "tag and diacylglycerol", "and diacylglycerol dag", "dag progresses through", "progresses through their hydrolysis", "through their hydrolysis by", "their hydrolysis by patatin", "hydrolysis by patatin like", "by patatin like phospholipase", "patatin like phospholipase domain", "like phospholipase domain containing", "phospholipase domain containing proteins", "domain containing proteins 2/3", "proteins 2/3 pnpla2/3", "2/3 pnpla2/3 .", "pnpla2/3 . dag", ". dag is", "dag is reacylated back", "is reacylated back to", "reacylated back to tag", "back to tag by", "to tag by acylglycerol", "tag by acylglycerol o", "by acylglycerol o acyltransferase", "acylglycerol o acyltransferase 1/2", "acyltransferase 1/2 dgat1/2", "dgat1/2 while", "while dag and its", "dag and its hydrolysis", "and its hydrolysis product", "its hydrolysis product 2", "hydrolysis product 2 monoacylglycerol", "2 monoacylglycerol 2", "monoacylglycerol 2 mag", "2 mag are", "mag are transacylated", "are transacylated back to", "transacylated back to tag", "to tag by pnpla2/3.", "by pnpla2/3. in", "pnpla2/3. in addition", "in addition the", "addition the dag", "the dag hydrolysis product", "dag hydrolysis product 2", "hydrolysis product 2 mag", "product 2 mag is", "2 mag is subsequently", "mag is subsequently hydrolyzed", "is subsequently hydrolyzed to", "subsequently hydrolyzed to fatty", "hydrolyzed to fatty acid", "to fatty acid and", "fatty acid and glycerol", "acid and glycerol by", "and glycerol by monoglyceride", "glycerol by monoglyceride lipase", "monoglyceride lipase mgll", "mgll jenkins", "jenkins et al. 2004", "et al. 2004 .", "acyl chain remodeling of triacylglycerol", "remodeling of triacylglycerol tag", "triacylglycerol tag and", "diacylglycerol dag progresses", "dag progresses through their", "progresses through their hydrolysis by", "through their hydrolysis by patatin", "their hydrolysis by patatin like", "hydrolysis by patatin like phospholipase", "by patatin like phospholipase domain", "patatin like phospholipase domain containing", "like phospholipase domain containing proteins", "phospholipase domain containing proteins 2/3", "containing proteins 2/3 pnpla2/3", "proteins 2/3 pnpla2/3 .", "pnpla2/3 . dag is", ". dag is reacylated", "dag is reacylated back to", "is reacylated back to tag", "reacylated back to tag by", "back to tag by acylglycerol", "to tag by acylglycerol o", "tag by acylglycerol o acyltransferase", "by acylglycerol o acyltransferase 1/2", "o acyltransferase 1/2 dgat1/2", "dgat1/2 while dag", "while dag and its hydrolysis", "dag and its hydrolysis product", "and its hydrolysis product 2", "its hydrolysis product 2 monoacylglycerol", "product 2 monoacylglycerol 2", "2 monoacylglycerol 2 mag", "2 mag are transacylated", "mag are transacylated back", "are transacylated back to tag", "transacylated back to tag by", "back to tag by pnpla2/3.", "tag by pnpla2/3. in", "by pnpla2/3. in addition", "in addition the dag", "addition the dag hydrolysis", "the dag hydrolysis product 2", "dag hydrolysis product 2 mag", "hydrolysis product 2 mag is", "product 2 mag is subsequently", "2 mag is subsequently hydrolyzed", "mag is subsequently hydrolyzed to", "is subsequently hydrolyzed to fatty", "subsequently hydrolyzed to fatty acid", "hydrolyzed to fatty acid and", "to fatty acid and glycerol", "fatty acid and glycerol by", "acid and glycerol by monoglyceride", "and glycerol by monoglyceride lipase", "by monoglyceride lipase mgll", "mgll jenkins et", "jenkins et al. 2004 ." ] }, { "record_id": "GLY_000594_1_770", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483206", "r hsa", "hsa 1483206", "r hsa 1483206" ] }, { "record_id": "GLY_000594_1_770", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycerophospholipid biosynthesis", "glycerophospholipids are", "are important", "important structural", "structural and", "and functional", "functional components", "components of", "of biological", "biological membranes", "membranes and", "and constituents", "constituents of", "of serum", "serum lipoproteins", "lipoproteins and", "and the", "the pulmonary", "pulmonary surfactant.", "in addition", "glycerophospholipids act", "act as", "as precursors", "precursors of", "of lipid", "lipid mediators", "mediators such", "such as", "as platelet", "platelet activating", "activating factor", "factor and", "and eicosanoids.", "cellular membranes", "membranes contains", "contains a", "a distinct", "distinct composition", "composition of", "of various", "various glycerophospholipids", "glycerophospholipids such", "as phosphatidic", "phosphatidic acid", "lysophosphatidic acid", "and lysobisphosphatidic", "lysobisphosphatidic acid", "also known", "known as", "as bis", "bis monoacylglycerol", "hydrogen phosphate", "bmp .

glycerophospholipids", ".

glycerophospholipids are", "are first", "first formed", "formed by", "by the", "the de", "de novo", "pathway using", "using fatty", "fatty acids", "acids activated", "activated as", "as acyl", "acyl coa", "coa donors.", "the acyl", "acyl groups", "groups of", "of glycerophospholipids", "are highly", "highly diverse", "diverse and", "and distributed", "distributed in", "in an", "an asymmetric", "asymmetric manner.", "saturated and", "and monounsaturated", "monounsaturated fatty", "acids are", "are usually", "usually esterified", "esterified at", "at the", "the sn", "sn 1", "1 position", "whereas polyunsaturated", "polyunsaturated acyl", "groups are", "are esterified", "sn 2", "2 position.", "subsequent acyl", "acyl chain", "chain remodeling", "lands cycle", "generates the", "the diverse", "diverse glycerophospholipid", "glycerophospholipid composition", "composition and", "and asymmetry", "asymmetry characteristic", "characteristic of", "of cell", "cell membranes.

in", "membranes.

in the", "novo pathway", "pathway of", "of glycerophospholipid", "is initially", "initially formed", "formed from", "from glycerol", "glycerol 3", "3 phosphate", "g3p .", "lpa is", "is converted", "converted to", "to pa", "pa by", "by a", "a lpa", "lpa acyltransferase", "as lpaat", "then pa", "pa is", "is metabolized", "metabolized into", "into two", "two types", "types of", "of glycerol", "glycerol derivatives.", "the first", "first is", "is diacylglycerol", "which is", "to triacylglycerol", "and pe.", "ps is", "is synthesized", "synthesized from", "from pc", "pc or", "or pe.", "the second", "second is", "is cytidine", "cytidine diphosphate", "diphosphate diacylglycerol", "cdp dag", "is processed", "processed into", "into pi", "and bmp.", "each glycerophospholipid", "glycerophospholipid is", "is involved", "involved in", "in acyl", "remodeling via", "via cleavage", "cleavage by", "by phospholipases", "phospholipases followed", "followed by", "by reacylation", "reacylation by", "by an", "an acyltransferase.

most", "acyltransferase.

most of", "of the", "the glycerophospholipids", "are synthesized", "synthesized at", "the endoplasmic", "endoplasmic reticulum", "most notably", "notably cardiolipin", "and bmp", "bmp are", "synthesized in", "in the", "the mitochondrial", "mitochondrial and", "and endosomal", "endosomal membranes", "membranes respectively.", "since the", "the most", "most of", "are found", "found in", "in all", "all membrane", "membrane compartments", "there must", "must be", "be extensive", "extensive network", "network of", "of transport", "transport of", "glycerophospholipids from", "from one", "one membrane", "membrane compartment", "compartment to", "to another", "another via", "via various", "various mechanisms", "mechanisms including", "including diffusion", "diffusion through", "through the", "the cytosol", "formation of", "of transportation", "transportation complexes", "and diffusion", "diffusion via", "via membrane", "membrane contact", "contact sites", "osman et", "et al.", "al. 2011", "lebiedzinska et", "al. 2009", "lev 2010", "scherer &", "& schmitz", "schmitz 2011", "orso et", "hermansson et", "vance &", "& vance", "vance 2008", "2008 .", "glycerophospholipids are important", "are important structural", "important structural and", "structural and functional", "and functional components", "functional components of", "components of biological", "of biological membranes", "biological membranes and", "membranes and constituents", "and constituents of", "constituents of serum", "of serum lipoproteins", "serum lipoproteins and", "lipoproteins and the", "and the pulmonary", "the pulmonary surfactant.", "surfactant. in", "addition glycerophospholipids", "glycerophospholipids act as", "act as precursors", "as precursors of", "precursors of lipid", "of lipid mediators", "lipid mediators such", "mediators such as", "such as platelet", "as platelet activating", "platelet activating factor", "activating factor and", "factor and eicosanoids.", "eicosanoids. cellular", "cellular membranes contains", "membranes contains a", "contains a distinct", "a distinct composition", "distinct composition of", "composition of various", "of various glycerophospholipids", "various glycerophospholipids such", "glycerophospholipids such as", "such as phosphatidic", "as phosphatidic acid", "acid pa", "phosphatidylcholine pc", "phosphatidylethanolamine pe", "phosphatidylserine ps", "phosphatidylglycerol pg", "phosphatidylinositol pi", "cardiolipin cl", "acid lpa", "lpa and", "and lysobisphosphatidic acid", "acid also", "also known as", "known as bis", "as bis monoacylglycerol", "monoacylglycerol hydrogen", "bmp .

glycerophospholipids are", ".

glycerophospholipids are first", "are first formed", "first formed by", "formed by the", "by the de", "the de novo", "novo kennedy", "kennedy pathway", "pathway using fatty", "using fatty acids", "fatty acids activated", "acids activated as", "activated as acyl", "as acyl coa", "acyl coa donors.", "donors. however", "however the", "the acyl groups", "acyl groups of", "groups of glycerophospholipids", "of glycerophospholipids are", "glycerophospholipids are highly", "are highly diverse", "highly diverse and", "diverse and distributed", "and distributed in", "distributed in an", "in an asymmetric", "an asymmetric manner.", "manner. saturated", "saturated and monounsaturated", "and monounsaturated fatty", "monounsaturated fatty acids", "fatty acids are", "acids are usually", "are usually esterified", "usually esterified at", "esterified at the", "at the sn", "the sn 1", "sn 1 position", "position whereas", "whereas polyunsaturated acyl", "polyunsaturated acyl groups", "acyl groups are", "groups are esterified", "are esterified at", "the sn 2", "sn 2 position.", "position. subsequent", "subsequent acyl chain", "acyl chain remodeling", "remodeling lands", "cycle generates", "generates the diverse", "the diverse glycerophospholipid", "diverse glycerophospholipid composition", "glycerophospholipid composition and", "composition and asymmetry", "and asymmetry characteristic", "asymmetry characteristic of", "characteristic of cell", "of cell membranes.

in", "cell membranes.

in the", "membranes.

in the de", "de novo pathway", "novo pathway of", "pathway of glycerophospholipid", "of glycerophospholipid biosynthesis", "biosynthesis lysophosphatidic", "is initially formed", "initially formed from", "formed from glycerol", "from glycerol 3", "glycerol 3 phosphate", "phosphate g3p", ". next", "next lpa", "lpa is converted", "is converted to", "converted to pa", "to pa by", "pa by a", "by a lpa", "a lpa acyltransferase", "acyltransferase agpat", "agpat also", "known as lpaat", "then pa is", "pa is metabolized", "is metabolized into", "metabolized into two", "into two types", "two types of", "types of glycerol", "of glycerol derivatives.", "derivatives. the", "the first is", "first is diacylglycerol", "diacylglycerol dag", "dag which", "which is converted", "converted to triacylglycerol", "triacylglycerol tag", "pc and", "pe. subsequently", "subsequently ps", "ps is synthesized", "is synthesized from", "synthesized from pc", "from pc or", "pc or pe.", "pe. the", "the second is", "second is cytidine", "is cytidine diphosphate", "cytidine diphosphate diacylglycerol", "diacylglycerol cdp", "which is processed", "is processed into", "processed into pi", "pi pg", "pg cl", "cl and", "bmp. each", "each glycerophospholipid is", "glycerophospholipid is involved", "is involved in", "involved in acyl", "in acyl chain", "chain remodeling via", "remodeling via cleavage", "via cleavage by", "cleavage by phospholipases", "by phospholipases followed", "phospholipases followed by", "followed by reacylation", "by reacylation by", "reacylation by an", "by an acyltransferase.

most", "an acyltransferase.

most of", "acyltransferase.

most of the", "of the glycerophospholipids", "the glycerophospholipids are", "glycerophospholipids are synthesized", "are synthesized at", "synthesized at the", "at the endoplasmic", "the endoplasmic reticulum", "reticulum er", "however some", "some most", "most notably cardiolipin", "cardiolipin and", "and bmp are", "bmp are synthesized", "are synthesized in", "synthesized in the", "in the mitochondrial", "the mitochondrial and", "mitochondrial and endosomal", "and endosomal membranes", "endosomal membranes respectively.", "respectively. since", "since the most", "the most of", "most of the", "glycerophospholipids are found", "are found in", "found in all", "in all membrane", "all membrane compartments", "compartments there", "there must be", "must be extensive", "be extensive network", "extensive network of", "network of transport", "of transport of", "transport of glycerophospholipids", "of glycerophospholipids from", "glycerophospholipids from one", "from one membrane", "one membrane compartment", "membrane compartment to", "compartment to another", "to another via", "another via various", "via various mechanisms", "various mechanisms including", "mechanisms including diffusion", "including diffusion through", "diffusion through the", "through the cytosol", "cytosol formation", "formation of transportation", "of transportation complexes", "complexes and", "and diffusion via", "diffusion via membrane", "via membrane contact", "membrane contact sites", "sites mcs", "osman et al.", "et al. 2011", "2011 lebiedzinska", "lebiedzinska et al.", "et al. 2009", "2009 lev", "2010 scherer", "scherer & schmitz", "& schmitz 2011", "2011 orso", "orso et al.", "2011 hermansson", "hermansson et al.", "2011 vance", "vance & vance", "& vance 2008", "vance 2008 .", "glycerophospholipids are important structural", "are important structural and", "important structural and functional", "structural and functional components", "and functional components of", "functional components of biological", "components of biological membranes", "of biological membranes and", "biological membranes and constituents", "membranes and constituents of", "and constituents of serum", "constituents of serum lipoproteins", "of serum lipoproteins and", "serum lipoproteins and the", "lipoproteins and the pulmonary", "and the pulmonary surfactant.", "pulmonary surfactant. in", "surfactant. in addition", "in addition glycerophospholipids", "addition glycerophospholipids act", "glycerophospholipids act as precursors", "act as precursors of", "as precursors of lipid", "precursors of lipid mediators", "of lipid mediators such", "lipid mediators such as", "mediators such as platelet", "such as platelet activating", "as platelet activating factor", "platelet activating factor and", "activating factor and eicosanoids.", "and eicosanoids. cellular", "eicosanoids. cellular membranes", "cellular membranes contains a", "membranes contains a distinct", "contains a distinct composition", "a distinct composition of", "distinct composition of various", "composition of various glycerophospholipids", "of various glycerophospholipids such", "various glycerophospholipids such as", "glycerophospholipids such as phosphatidic", "such as phosphatidic acid", "phosphatidic acid pa", "pa phosphatidylcholine", "pc phosphatidylethanolamine", "pe phosphatidylserine", "ps phosphatidylglycerol", "pg phosphatidylinositol", "pi cardiolipin", "cl lysophosphatidic", "lysophosphatidic acid lpa", "lpa and lysobisphosphatidic", "lysobisphosphatidic acid also", "acid also known", "also known as bis", "known as bis monoacylglycerol", "bis monoacylglycerol hydrogen", "monoacylglycerol hydrogen phosphate", "phosphate bmp", "bmp .

glycerophospholipids are first", ".

glycerophospholipids are first formed", "are first formed by", "first formed by the", "formed by the de", "by the de novo", "de novo kennedy", "kennedy pathway using", "pathway using fatty acids", "using fatty acids activated", "fatty acids activated as", "acids activated as acyl", "activated as acyl coa", "as acyl coa donors.", "coa donors. however", "however the acyl", "the acyl groups of", "acyl groups of glycerophospholipids", "groups of glycerophospholipids are", "of glycerophospholipids are highly", "glycerophospholipids are highly diverse", "are highly diverse and", "highly diverse and distributed", "diverse and distributed in", "and distributed in an", "distributed in an asymmetric", "in an asymmetric manner.", "asymmetric manner. saturated", "manner. saturated and", "saturated and monounsaturated fatty", "and monounsaturated fatty acids", "monounsaturated fatty acids are", "fatty acids are usually", "acids are usually esterified", "are usually esterified at", "usually esterified at the", "esterified at the sn", "at the sn 1", "the sn 1 position", "1 position whereas", "position whereas polyunsaturated", "whereas polyunsaturated acyl groups", "polyunsaturated acyl groups are", "acyl groups are esterified", "groups are esterified at", "are esterified at the", "at the sn 2", "the sn 2 position.", "2 position. subsequent", "position. subsequent acyl", "subsequent acyl chain remodeling", "chain remodeling lands", "remodeling lands cycle", "lands cycle generates", "cycle generates the", "generates the diverse glycerophospholipid", "the diverse glycerophospholipid composition", "diverse glycerophospholipid composition and", "glycerophospholipid composition and asymmetry", "composition and asymmetry characteristic", "and asymmetry characteristic of", "asymmetry characteristic of cell", "characteristic of cell membranes.

in", "of cell membranes.

in the", "cell membranes.

in the de", "membranes.

in the de novo", "the de novo pathway", "de novo pathway of", "novo pathway of glycerophospholipid", "pathway of glycerophospholipid biosynthesis", "glycerophospholipid biosynthesis lysophosphatidic", "biosynthesis lysophosphatidic acid", "lpa is initially", "is initially formed from", "initially formed from glycerol", "formed from glycerol 3", "from glycerol 3 phosphate", "3 phosphate g3p", "phosphate g3p .", "g3p . next", "next lpa is", "lpa is converted to", "is converted to pa", "converted to pa by", "to pa by a", "pa by a lpa", "by a lpa acyltransferase", "lpa acyltransferase agpat", "agpat also known", "also known as lpaat", "lpaat then", "then pa is metabolized", "pa is metabolized into", "is metabolized into two", "metabolized into two types", "into two types of", "two types of glycerol", "types of glycerol derivatives.", "glycerol derivatives. the", "derivatives. the first", "the first is diacylglycerol", "is diacylglycerol dag", "dag which is", "which is converted to", "is converted to triacylglycerol", "to triacylglycerol tag", "tag pc", "pc and pe.", "and pe. subsequently", "subsequently ps is", "ps is synthesized from", "is synthesized from pc", "synthesized from pc or", "from pc or pe.", "or pe. the", "pe. the second", "the second is cytidine", "second is cytidine diphosphate", "is cytidine diphosphate diacylglycerol", "diphosphate diacylglycerol cdp", "diacylglycerol cdp dag", "which is processed into", "is processed into pi", "into pi pg", "cl and bmp.", "and bmp. each", "bmp. each glycerophospholipid", "each glycerophospholipid is involved", "glycerophospholipid is involved in", "is involved in acyl", "involved in acyl chain", "in acyl chain remodeling", "acyl chain remodeling via", "chain remodeling via cleavage", "remodeling via cleavage by", "via cleavage by phospholipases", "cleavage by phospholipases followed", "by phospholipases followed by", "phospholipases followed by reacylation", "followed by reacylation by", "by reacylation by an", "reacylation by an acyltransferase.

most", "by an acyltransferase.

most of", "an acyltransferase.

most of the", "acyltransferase.

most of the glycerophospholipids", "of the glycerophospholipids are", "the glycerophospholipids are synthesized", "glycerophospholipids are synthesized at", "are synthesized at the", "synthesized at the endoplasmic", "at the endoplasmic reticulum", "endoplasmic reticulum er", "er however", "some most notably", "notably cardiolipin and", "cardiolipin and bmp", "and bmp are synthesized", "bmp are synthesized in", "are synthesized in the", "synthesized in the mitochondrial", "in the mitochondrial and", "the mitochondrial and endosomal", "mitochondrial and endosomal membranes", "and endosomal membranes respectively.", "membranes respectively. since", "respectively. since the", "since the most of", "the most of the", "most of the glycerophospholipids", "the glycerophospholipids are found", "glycerophospholipids are found in", "are found in all", "found in all membrane", "in all membrane compartments", "membrane compartments there", "compartments there must", "there must be extensive", "must be extensive network", "be extensive network of", "extensive network of transport", "network of transport of", "of transport of glycerophospholipids", "transport of glycerophospholipids from", "of glycerophospholipids from one", "glycerophospholipids from one membrane", "from one membrane compartment", "one membrane compartment to", "membrane compartment to another", "compartment to another via", "to another via various", "another via various mechanisms", "via various mechanisms including", "various mechanisms including diffusion", "mechanisms including diffusion through", "including diffusion through the", "diffusion through the cytosol", "the cytosol formation", "cytosol formation of", "formation of transportation complexes", "transportation complexes and", "complexes and diffusion", "and diffusion via membrane", "diffusion via membrane contact", "via membrane contact sites", "contact sites mcs", "mcs osman", "osman et al. 2011", "al. 2011 lebiedzinska", "2011 lebiedzinska et", "lebiedzinska et al. 2009", "al. 2009 lev", "2009 lev 2010", "lev 2010 scherer", "2010 scherer &", "scherer & schmitz 2011", "schmitz 2011 orso", "2011 orso et", "orso et al. 2011", "al. 2011 hermansson", "2011 hermansson et", "hermansson et al. 2011", "al. 2011 vance", "2011 vance &", "vance & vance 2008", "& vance 2008 .", "glycerophospholipids are important structural and", "are important structural and functional", "important structural and functional components", "structural and functional components of", "and functional components of biological", "functional components of biological membranes", "components of biological membranes and", "of biological membranes and constituents", "biological membranes and constituents of", "membranes and constituents of serum", "and constituents of serum lipoproteins", "constituents of serum lipoproteins and", "of serum lipoproteins and the", "serum lipoproteins and the pulmonary", "lipoproteins and the pulmonary surfactant.", "the pulmonary surfactant. in", "pulmonary surfactant. in addition", "in addition glycerophospholipids act", "addition glycerophospholipids act as", "glycerophospholipids act as precursors of", "act as precursors of lipid", "as precursors of lipid mediators", "precursors of lipid mediators such", "of lipid mediators such as", "lipid mediators such as platelet", "mediators such as platelet activating", "such as platelet activating factor", "as platelet activating factor and", "platelet activating factor and eicosanoids.", "factor and eicosanoids. cellular", "and eicosanoids. cellular membranes", "eicosanoids. cellular membranes contains", "cellular membranes contains a distinct", "membranes contains a distinct composition", "contains a distinct composition of", "a distinct composition of various", "distinct composition of various glycerophospholipids", "composition of various glycerophospholipids such", "of various glycerophospholipids such as", "various glycerophospholipids such as phosphatidic", "glycerophospholipids such as phosphatidic acid", "as phosphatidic acid pa", "cl lysophosphatidic acid", "acid lpa and", "lpa and lysobisphosphatidic acid", "and lysobisphosphatidic acid also", "lysobisphosphatidic acid also known", "acid also known as", "also known as bis monoacylglycerol", "as bis monoacylglycerol hydrogen", "bis monoacylglycerol hydrogen phosphate", "hydrogen phosphate bmp", "phosphate bmp .

glycerophospholipids", "bmp .

glycerophospholipids are first formed", ".

glycerophospholipids are first formed by", "are first formed by the", "first formed by the de", "formed by the de novo", "the de novo kennedy", "novo kennedy pathway", "kennedy pathway using fatty", "pathway using fatty acids activated", "using fatty acids activated as", "fatty acids activated as acyl", "acids activated as acyl coa", "activated as acyl coa donors.", "acyl coa donors. however", "donors. however the", "however the acyl groups", "the acyl groups of glycerophospholipids", "acyl groups of glycerophospholipids are", "groups of glycerophospholipids are highly", "of glycerophospholipids are highly diverse", "glycerophospholipids are highly diverse and", "are highly diverse and distributed", "highly diverse and distributed in", "diverse and distributed in an", "and distributed in an asymmetric", "distributed in an asymmetric manner.", "an asymmetric manner. saturated", "asymmetric manner. saturated and", "manner. saturated and monounsaturated", "saturated and monounsaturated fatty acids", "and monounsaturated fatty acids are", "monounsaturated fatty acids are usually", "fatty acids are usually esterified", "acids are usually esterified at", "are usually esterified at the", "usually esterified at the sn", "esterified at the sn 1", "at the sn 1 position", "sn 1 position whereas", "1 position whereas polyunsaturated", "position whereas polyunsaturated acyl", "whereas polyunsaturated acyl groups are", "polyunsaturated acyl groups are esterified", "acyl groups are esterified at", "groups are esterified at the", "are esterified at the sn", "esterified at the sn 2", "at the sn 2 position.", "sn 2 position. subsequent", "2 position. subsequent acyl", "position. subsequent acyl chain", "acyl chain remodeling lands", "chain remodeling lands cycle", "lands cycle generates the", "cycle generates the diverse", "generates the diverse glycerophospholipid composition", "the diverse glycerophospholipid composition and", "diverse glycerophospholipid composition and asymmetry", "glycerophospholipid composition and asymmetry characteristic", "composition and asymmetry characteristic of", "and asymmetry characteristic of cell", "asymmetry characteristic of cell membranes.

in", "characteristic of cell membranes.

in the", "of cell membranes.

in the de", "cell membranes.

in the de novo", "membranes.

in the de novo pathway", "the de novo pathway of", "de novo pathway of glycerophospholipid", "novo pathway of glycerophospholipid biosynthesis", "of glycerophospholipid biosynthesis lysophosphatidic", "glycerophospholipid biosynthesis lysophosphatidic acid", "acid lpa is", "lpa is initially formed", "is initially formed from glycerol", "initially formed from glycerol 3", "formed from glycerol 3 phosphate", "glycerol 3 phosphate g3p", "3 phosphate g3p .", ". next lpa", "next lpa is converted", "lpa is converted to pa", "is converted to pa by", "converted to pa by a", "to pa by a lpa", "pa by a lpa acyltransferase", "a lpa acyltransferase agpat", "acyltransferase agpat also", "agpat also known as", "as lpaat then", "lpaat then pa", "then pa is metabolized into", "pa is metabolized into two", "is metabolized into two types", "metabolized into two types of", "into two types of glycerol", "two types of glycerol derivatives.", "of glycerol derivatives. the", "glycerol derivatives. the first", "derivatives. the first is", "first is diacylglycerol dag", "diacylglycerol dag which", "dag which is converted", "which is converted to triacylglycerol", "converted to triacylglycerol tag", "pe. subsequently ps", "subsequently ps is synthesized", "ps is synthesized from pc", "is synthesized from pc or", "synthesized from pc or pe.", "pc or pe. the", "or pe. the second", "pe. the second is", "the second is cytidine diphosphate", "second is cytidine diphosphate diacylglycerol", "cytidine diphosphate diacylglycerol cdp", "diphosphate diacylglycerol cdp dag", "cdp dag which", "which is processed into pi", "processed into pi pg", "pi pg cl", "pg cl and", "and bmp. each glycerophospholipid", "bmp. each glycerophospholipid is", "each glycerophospholipid is involved in", "glycerophospholipid is involved in acyl", "is involved in acyl chain", "involved in acyl chain remodeling", "in acyl chain remodeling via", "acyl chain remodeling via cleavage", "chain remodeling via cleavage by", "remodeling via cleavage by phospholipases", "via cleavage by phospholipases followed", "cleavage by phospholipases followed by", "by phospholipases followed by reacylation", "phospholipases followed by reacylation by", "followed by reacylation by an", "by reacylation by an acyltransferase.

most", "reacylation by an acyltransferase.

most of", "by an acyltransferase.

most of the", "an acyltransferase.

most of the glycerophospholipids", "acyltransferase.

most of the glycerophospholipids are", "of the glycerophospholipids are synthesized", "the glycerophospholipids are synthesized at", "glycerophospholipids are synthesized at the", "are synthesized at the endoplasmic", "synthesized at the endoplasmic reticulum", "the endoplasmic reticulum er", "however some most", "some most notably cardiolipin", "most notably cardiolipin and", "notably cardiolipin and bmp", "cardiolipin and bmp are", "and bmp are synthesized in", "bmp are synthesized in the", "are synthesized in the mitochondrial", "synthesized in the mitochondrial and", "in the mitochondrial and endosomal", "the mitochondrial and endosomal membranes", "mitochondrial and endosomal membranes respectively.", "endosomal membranes respectively. since", "membranes respectively. since the", "respectively. since the most", "since the most of the", "the most of the glycerophospholipids", "most of the glycerophospholipids are", "of the glycerophospholipids are found", "the glycerophospholipids are found in", "glycerophospholipids are found in all", "are found in all membrane", "found in all membrane compartments", "all membrane compartments there", "membrane compartments there must", "compartments there must be", "there must be extensive network", "must be extensive network of", "be extensive network of transport", "extensive network of transport of", "network of transport of glycerophospholipids", "of transport of glycerophospholipids from", "transport of glycerophospholipids from one", "of glycerophospholipids from one membrane", "glycerophospholipids from one membrane compartment", "from one membrane compartment to", "one membrane compartment to another", "membrane compartment to another via", "compartment to another via various", "to another via various mechanisms", "another via various mechanisms including", "via various mechanisms including diffusion", "various mechanisms including diffusion through", "mechanisms including diffusion through the", "including diffusion through the cytosol", "through the cytosol formation", "the cytosol formation of", "cytosol formation of transportation", "of transportation complexes and", "transportation complexes and diffusion", "complexes and diffusion via", "and diffusion via membrane contact", "diffusion via membrane contact sites", "membrane contact sites mcs", "mcs osman et", "et al. 2011 lebiedzinska", "al. 2011 lebiedzinska et", "2011 lebiedzinska et al.", "et al. 2009 lev", "al. 2009 lev 2010", "lev 2010 scherer &", "2010 scherer & schmitz", "& schmitz 2011 orso", "schmitz 2011 orso et", "2011 orso et al.", "et al. 2011 hermansson", "al. 2011 hermansson et", "2011 hermansson et al.", "et al. 2011 vance", "al. 2011 vance &", "2011 vance & vance", "vance & vance 2008 ." ] }, { "record_id": "GLY_000594_1_771", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483248", "r hsa", "hsa 1483248", "r hsa 1483248" ] }, { "record_id": "GLY_000594_1_771", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pips", "pips at", "at the", "the er", "er membrane", "synthesis of pips", "of pips at", "pips at the", "at the er", "the er membrane", "synthesis of pips at", "of pips at the", "pips at the er", "at the er membrane", "synthesis of pips at the", "of pips at the er", "pips at the er membrane", "the endoplasmic", "endoplasmic reticulum", "and phosphatidylinositol", "phosphatidylinositol 4", "4 phosphate", "are interconverted", "wong et", "et al.", "al. 1997", "gehrmann et", "al. 1999", "wei et", "al. 2002", "rohde et", "al. 2003", "2003 .", "at the endoplasmic", "the endoplasmic reticulum", "reticulum er", "membrane phosphatidylinositol", "phosphatidylinositol pi", "pi and", "and phosphatidylinositol 4", "phosphatidylinositol 4 phosphate", "phosphate pi4p", "pi4p are", "interconverted wong", "wong et al.", "et al. 1997", "1997 gehrmann", "gehrmann et al.", "et al. 1999", "1999 wei", "wei et al.", "et al. 2002", "2002 rohde", "rohde et al.", "et al. 2003", "al. 2003 .", "at the endoplasmic reticulum", "endoplasmic reticulum er", "pi and phosphatidylinositol", "and phosphatidylinositol 4 phosphate", "4 phosphate pi4p", "pi4p are interconverted", "are interconverted wong", "interconverted wong et", "wong et al. 1997", "al. 1997 gehrmann", "1997 gehrmann et", "gehrmann et al. 1999", "al. 1999 wei", "1999 wei et", "wei et al. 2002", "al. 2002 rohde", "2002 rohde et", "rohde et al. 2003", "et al. 2003 .", "the endoplasmic reticulum er", "reticulum er membrane", "er membrane phosphatidylinositol", "membrane phosphatidylinositol pi", "phosphatidylinositol pi and", "pi and phosphatidylinositol 4", "phosphatidylinositol 4 phosphate pi4p", "phosphate pi4p are", "are interconverted wong et", "interconverted wong et al.", "et al. 1997 gehrmann", "al. 1997 gehrmann et", "1997 gehrmann et al.", "et al. 1999 wei", "al. 1999 wei et", "1999 wei et al.", "et al. 2002 rohde", "al. 2002 rohde et", "2002 rohde et al.", "rohde et al. 2003 ." ] }, { "record_id": "GLY_000594_1_772", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483255", "r hsa", "hsa 1483255", "r hsa 1483255" ] }, { "record_id": "GLY_000594_1_772", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi metabolism", "a membrane", "membrane phospholipid", "can be", "be reversibly", "reversibly phosphorylated", "phosphorylated at", "at the", "the 3", "and 5", "5 positions", "positions of", "of the", "the inositol", "inositol ring", "ring to", "to generate", "generate seven", "seven phosphoinositides:", "phosphoinositides: phosphatidylinositol", "phosphatidylinositol 3", "3 phosphate", "phosphatidylinositol 4", "4 phosphate", "phosphatidylinositol 5", "5 phosphate", "3 4", "4 bisphosphate", "bisphosphate pi", "pi 3", "4 p2", "4 5", "5 bisphosphate", "pi 4", "5 p2", "3 5", "and phosphatidylinositol", "5 trisphosphate", "5 p3", "p3 .", ". these", "these seven", "seven phosphoinositides", "which are", "are heterogeneously", "heterogeneously distributed", "distributed within", "within cells", "can serve", "serve as", "as signature", "signature components", "components of", "of different", "different intracellular", "intracellular compartment", "compartment membranes", "membranes and", "and so", "so help", "help to", "to mediate", "mediate specificity", "specificity of", "of membrane", "membrane interactions.", "interactions. phosphoinositide", "phosphoinositide levels", "levels are", "are tightly", "tightly regulated", "regulated spatially", "spatially and", "and temporally", "temporally by", "by the", "the action", "action of", "of various", "various kinases", "kinases and", "and phosphatases", "phosphatases whilst", "whilst pi", "p2 is", "is also", "also a", "a substrate", "substrate for", "for phospholipase", "phospholipase c.", "c. the", "the differential", "differential localisation", "localisation of", "of each", "each of", "of these", "these enzymes", "enzymes on", "on specific", "specific compartment", "membranes ensures", "ensures maintenance", "maintenance of", "the heterogeneous", "heterogeneous distribution", "distribution of", "of phosphoinositides", "phosphoinositides despite", "despite the", "the continuous", "continuous membrane", "membrane flow", "flow from", "from one", "one compartment", "compartment to", "to another.

pi", "another.

pi is", "is primarily", "primarily synthesised", "synthesised in", "in the", "the endoplasmic", "endoplasmic reticulum", "reticulum from", "from where", "where the", "the phospholipid", "phospholipid is", "is exported", "exported to", "to other", "other compartments", "compartments via", "via membrane", "membrane traffic", "traffic or", "or via", "via cytosolic", "cytosolic phospholipid", "phospholipid transfer", "transfer proteins.", "proteins. phosphorylation", "phosphorylation of", "of pi", "pi to", "to pi4p", "pi4p primarily", "primarily occurs", "occurs in", "the golgi", "where pi4p", "pi4p plays", "plays an", "an important", "important role", "role in", "the biogenesis", "biogenesis of", "of transport", "transport vesicles", "vesicles such", "such as", "as the", "the secretory", "secretory vesicle", "vesicle involved", "involved in", "in its", "its transport", "transport to", "to the", "the plasma", "plasma membrane.", "membrane. at", "at this", "this place", "pi4p has", "has a", "a major", "major function", "function acting", "acting as", "as a", "a precursor", "precursor of", "which is", "is located", "located predominantly", "predominantly at", "this membrane.", "membrane. pi", "p2 binds", "binds and", "and regulates", "regulates a", "a wide", "wide range", "range of", "of proteins", "proteins that", "that function", "function on", "on the", "the cell", "cell surface", "surface and", "and serves", "serves as", "precursor for", "for second", "second messengers.", "messengers. additionally", "it helps", "helps define", "define this", "this membrane", "membrane as", "a target", "target for", "for secretory", "secretory vesicles", "functions as", "a coreceptor", "coreceptor in", "in endocytic", "endocytic processes", "and functions", "a cofactor", "cofactor for", "for actin", "actin nucleation.

at", "nucleation.

at the", "plasma membrane", "is further", "further phosphorylated", "phosphorylated to", "to pi", "another phosphoinositide", "phosphoinositide with", "with important", "important signalling", "signalling functions", "functions including", "including stimulating", "stimulating cell", "cell survival", "survival and", "and proliferation.", "proliferation. the", "inositol 3", "3 phosphatase", "phosphatase and", "and tensin", "tensin homolog", "regenerates pi", "while the", "the 5", "5 phosphatases", "phosphatases convert", "convert pi", "p3 into", "into the", "the phosphoinositide", "propagating the", "the signal", "signal initiated", "initiated by", "by pi", "5 p3.", "p3. pi", "further dephosphorylated", "dephosphorylated in", "the endocytic", "endocytic pathway", "pathway by", "by inositol", "inositol 4", "4 phosphatases", "phosphatases to", "to pi3p", "the signature", "signature phosphoinositide", "phosphoinositide of", "the early", "early endosomal", "endosomal compartment", "compartment and", "and a", "a ligand", "ligand for", "for numerous", "numerous endosomal", "endosomal proteins.", "proteins. however", "the bulk", "bulk of", "of pi3p", "pi3p is", "is generated", "generated directly", "directly in", "the endosomes", "endosomes by", "by phosphorylation", "of pi.", "pi. the", "the subsequent", "subsequent endosomal", "endosomal phosphorylation", "pi3p to", "is believed", "believed to", "generate docking", "docking sites", "sites for", "for recruitment", "recruitment of", "of cytosolic", "cytosolic factors", "factors responsible", "responsible for", "for the", "the control", "control of", "of outgoing", "outgoing traffic", "traffic from", "from the", "the endosomes.", "endosomes. the", "the main", "main localisation", "localisation and", "and function", "function of", "the low", "low abundance", "abundance phosphoinositide", "phosphoinositide pi5p", "that can", "be generated", "generated by", "by several", "several pathways", "remains to", "to be", "be determined", "krauss &", "& haucke", "haucke 2007", "leventis &", "& grinstein", "grinstein 2010", "roth 2004", "gees et", "et al.", "al. 2010", "de matteis", "matteis &", "& godi", "godi 2004", "van meer", "meer et", "al. 2008", "vicinanza et", "lemmon 2008", "kutaleladze 2010", "robinson &", "& dixon", "dixon 2006", "blero et", "al. 2007", "liu &", "& bankaitis", "bankaitis 2010", "mccrea &", "& de", "de camilli", "camilli 2009", "di paolo", "paolo &", "2006 .", "phosphatidylinositol pi", "a membrane phospholipid", "phospholipid can", "can be reversibly", "be reversibly phosphorylated", "reversibly phosphorylated at", "phosphorylated at the", "at the 3", "4 and", "and 5 positions", "5 positions of", "positions of the", "of the inositol", "the inositol ring", "inositol ring to", "ring to generate", "to generate seven", "generate seven phosphoinositides:", "seven phosphoinositides: phosphatidylinositol", "phosphoinositides: phosphatidylinositol 3", "phosphatidylinositol 3 phosphate", "phosphate pi3p", "phosphatidylinositol 4 phosphate", "phosphate pi4p", "phosphatidylinositol 5 phosphate", "phosphate pi5p", "phosphatidylinositol 3 4", "3 4 bisphosphate", "4 bisphosphate pi", "bisphosphate pi 3", "pi 3 4", "3 4 p2", "p2 phosphatidylinositol", "phosphatidylinositol 4 5", "4 5 bisphosphate", "5 bisphosphate pi", "bisphosphate pi 4", "pi 4 5", "4 5 p2", "phosphatidylinositol 3 5", "3 5 bisphosphate", "pi 3 5", "3 5 p2", "p2 and", "and phosphatidylinositol 3", "3 4 5", "4 5 trisphosphate", "trisphosphate pi", "4 5 p3", "5 p3 .", "p3 . these", ". these seven", "these seven phosphoinositides", "phosphoinositides which", "which are heterogeneously", "are heterogeneously distributed", "heterogeneously distributed within", "distributed within cells", "cells can", "can serve as", "serve as signature", "as signature components", "signature components of", "components of different", "of different intracellular", "different intracellular compartment", "intracellular compartment membranes", "compartment membranes and", "membranes and so", "and so help", "so help to", "help to mediate", "to mediate specificity", "mediate specificity of", "specificity of membrane", "of membrane interactions.", "membrane interactions. phosphoinositide", "interactions. phosphoinositide levels", "phosphoinositide levels are", "levels are tightly", "are tightly regulated", "tightly regulated spatially", "regulated spatially and", "spatially and temporally", "and temporally by", "temporally by the", "by the action", "the action of", "action of various", "of various kinases", "various kinases and", "kinases and phosphatases", "and phosphatases whilst", "phosphatases whilst pi", "whilst pi 4", "5 p2 is", "p2 is also", "is also a", "also a substrate", "a substrate for", "substrate for phospholipase", "for phospholipase c.", "phospholipase c. the", "c. the differential", "the differential localisation", "differential localisation of", "localisation of each", "of each of", "each of these", "of these enzymes", "these enzymes on", "enzymes on specific", "on specific compartment", "specific compartment membranes", "compartment membranes ensures", "membranes ensures maintenance", "ensures maintenance of", "maintenance of the", "of the heterogeneous", "the heterogeneous distribution", "heterogeneous distribution of", "distribution of phosphoinositides", "of phosphoinositides despite", "phosphoinositides despite the", "despite the continuous", "the continuous membrane", "continuous membrane flow", "membrane flow from", "flow from one", "from one compartment", "one compartment to", "compartment to another.

pi", "to another.

pi is", "another.

pi is primarily", "is primarily synthesised", "primarily synthesised in", "synthesised in the", "in the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum from", "reticulum from where", "from where the", "where the phospholipid", "the phospholipid is", "phospholipid is exported", "is exported to", "exported to other", "to other compartments", "other compartments via", "compartments via membrane", "via membrane traffic", "membrane traffic or", "traffic or via", "or via cytosolic", "via cytosolic phospholipid", "cytosolic phospholipid transfer", "phospholipid transfer proteins.", "transfer proteins. phosphorylation", "proteins. phosphorylation of", "phosphorylation of pi", "of pi to", "pi to pi4p", "to pi4p primarily", "pi4p primarily occurs", "primarily occurs in", "occurs in the", "in the golgi", "golgi where", "where pi4p plays", "pi4p plays an", "plays an important", "an important role", "important role in", "role in the", "in the biogenesis", "the biogenesis of", "biogenesis of transport", "of transport vesicles", "transport vesicles such", "vesicles such as", "such as the", "as the secretory", "the secretory vesicle", "secretory vesicle involved", "vesicle involved in", "involved in its", "in its transport", "its transport to", "transport to the", "to the plasma", "the plasma membrane.", "plasma membrane. at", "membrane. at this", "at this place", "place pi4p", "pi4p has a", "has a major", "a major function", "major function acting", "function acting as", "acting as a", "as a precursor", "a precursor of", "precursor of pi", "of pi 4", "p2 which", "which is located", "is located predominantly", "located predominantly at", "predominantly at this", "at this membrane.", "this membrane. pi", "membrane. pi 4", "5 p2 binds", "p2 binds and", "binds and regulates", "and regulates a", "regulates a wide", "a wide range", "wide range of", "range of proteins", "of proteins that", "proteins that function", "that function on", "function on the", "on the cell", "the cell surface", "cell surface and", "surface and serves", "and serves as", "serves as a", "a precursor for", "precursor for second", "for second messengers.", "second messengers. additionally", "additionally it", "it helps define", "helps define this", "define this membrane", "this membrane as", "membrane as a", "as a target", "a target for", "target for secretory", "for secretory vesicles", "vesicles functions", "functions as a", "as a coreceptor", "a coreceptor in", "coreceptor in endocytic", "in endocytic processes", "processes and", "and functions as", "as a cofactor", "a cofactor for", "cofactor for actin", "for actin nucleation.

at", "actin nucleation.

at the", "nucleation.

at the plasma", "the plasma membrane", "membrane pi", "p2 is further", "is further phosphorylated", "further phosphorylated to", "phosphorylated to pi", "to pi 3", "p3 another", "another phosphoinositide with", "phosphoinositide with important", "with important signalling", "important signalling functions", "signalling functions including", "functions including stimulating", "including stimulating cell", "stimulating cell survival", "cell survival and", "survival and proliferation.", "and proliferation. the", "proliferation. the inositol", "the inositol 3", "inositol 3 phosphatase", "phosphatase phosphatase", "phosphatase and tensin", "and tensin homolog", "homolog pten", "pten regenerates", "regenerates pi 4", "p2 while", "while the 5", "the 5 phosphatases", "5 phosphatases convert", "phosphatases convert pi", "convert pi 3", "5 p3 into", "p3 into the", "into the phosphoinositide", "phosphoinositide pi", "p2 propagating", "propagating the signal", "the signal initiated", "signal initiated by", "initiated by pi", "by pi 3", "4 5 p3.", "5 p3. pi", "p3. pi 3", "4 p2 is", "is further dephosphorylated", "further dephosphorylated in", "dephosphorylated in the", "in the endocytic", "the endocytic pathway", "endocytic pathway by", "pathway by inositol", "by inositol 4", "inositol 4 phosphatases", "4 phosphatases to", "phosphatases to pi3p", "pi3p the", "the signature phosphoinositide", "signature phosphoinositide of", "phosphoinositide of the", "of the early", "the early endosomal", "early endosomal compartment", "endosomal compartment and", "compartment and a", "and a ligand", "a ligand for", "ligand for numerous", "for numerous endosomal", "numerous endosomal proteins.", "endosomal proteins. however", "however the", "the bulk of", "bulk of pi3p", "of pi3p is", "pi3p is generated", "is generated directly", "generated directly in", "directly in the", "in the endosomes", "the endosomes by", "endosomes by phosphorylation", "by phosphorylation of", "phosphorylation of pi.", "of pi. the", "pi. the subsequent", "the subsequent endosomal", "subsequent endosomal phosphorylation", "endosomal phosphorylation of", "phosphorylation of pi3p", "of pi3p to", "pi3p to pi", "p2 is believed", "is believed to", "believed to generate", "to generate docking", "generate docking sites", "docking sites for", "sites for recruitment", "for recruitment of", "recruitment of cytosolic", "of cytosolic factors", "cytosolic factors responsible", "factors responsible for", "responsible for the", "for the control", "the control of", "control of outgoing", "of outgoing traffic", "outgoing traffic from", "traffic from the", "from the endosomes.", "the endosomes. the", "endosomes. the main", "the main localisation", "main localisation and", "localisation and function", "and function of", "function of the", "of the low", "the low abundance", "low abundance phosphoinositide", "abundance phosphoinositide pi5p", "pi5p that", "that can be", "can be generated", "be generated by", "generated by several", "by several pathways", "pathways remains", "remains to be", "to be determined", "determined krauss", "krauss & haucke", "& haucke 2007", "2007 leventis", "leventis & grinstein", "& grinstein 2010", "2010 roth", "2004 gees", "gees et al.", "et al. 2010", "2010 de", "de matteis &", "matteis & godi", "& godi 2004", "2004 van", "van meer et", "meer et al.", "et al. 2008", "2008 vicinanza", "vicinanza et al.", "2008 lemmon", "2008 kutaleladze", "2010 robinson", "robinson & dixon", "& dixon 2006", "2006 blero", "blero et al.", "et al. 2007", "2007 liu", "liu & bankaitis", "& bankaitis 2010", "2010 mccrea", "mccrea & de", "& de camilli", "de camilli 2009", "2009 vicinanza", "2008 di", "di paolo &", "paolo & de", "camilli 2006", "pi a", "membrane phospholipid can", "phospholipid can be", "can be reversibly phosphorylated", "be reversibly phosphorylated at", "reversibly phosphorylated at the", "phosphorylated at the 3", "the 3 4", "4 and 5", "and 5 positions of", "5 positions of the", "positions of the inositol", "of the inositol ring", "the inositol ring to", "inositol ring to generate", "ring to generate seven", "to generate seven phosphoinositides:", "generate seven phosphoinositides: phosphatidylinositol", "seven phosphoinositides: phosphatidylinositol 3", "phosphoinositides: phosphatidylinositol 3 phosphate", "3 phosphate pi3p", "pi3p phosphatidylinositol", "4 phosphate pi4p", "pi4p phosphatidylinositol", "5 phosphate pi5p", "pi5p phosphatidylinositol", "phosphatidylinositol 3 4 bisphosphate", "3 4 bisphosphate pi", "4 bisphosphate pi 3", "bisphosphate pi 3 4", "pi 3 4 p2", "4 p2 phosphatidylinositol", "p2 phosphatidylinositol 4", "phosphatidylinositol 4 5 bisphosphate", "4 5 bisphosphate pi", "5 bisphosphate pi 4", "bisphosphate pi 4 5", "pi 4 5 p2", "5 p2 phosphatidylinositol", "p2 phosphatidylinositol 3", "phosphatidylinositol 3 5 bisphosphate", "3 5 bisphosphate pi", "5 bisphosphate pi 3", "bisphosphate pi 3 5", "pi 3 5 p2", "5 p2 and", "p2 and phosphatidylinositol", "and phosphatidylinositol 3 4", "phosphatidylinositol 3 4 5", "3 4 5 trisphosphate", "5 trisphosphate pi", "trisphosphate pi 3", "pi 3 4 5", "3 4 5 p3", "4 5 p3 .", "5 p3 . these", "p3 . these seven", ". these seven phosphoinositides", "seven phosphoinositides which", "phosphoinositides which are", "which are heterogeneously distributed", "are heterogeneously distributed within", "heterogeneously distributed within cells", "within cells can", "cells can serve", "can serve as signature", "serve as signature components", "as signature components of", "signature components of different", "components of different intracellular", "of different intracellular compartment", "different intracellular compartment membranes", "intracellular compartment membranes and", "compartment membranes and so", "membranes and so help", "and so help to", "so help to mediate", "help to mediate specificity", "to mediate specificity of", "mediate specificity of membrane", "specificity of membrane interactions.", "of membrane interactions. phosphoinositide", "membrane interactions. phosphoinositide levels", "interactions. phosphoinositide levels are", "phosphoinositide levels are tightly", "levels are tightly regulated", "are tightly regulated spatially", "tightly regulated spatially and", "regulated spatially and temporally", "spatially and temporally by", "and temporally by the", "temporally by the action", "by the action of", "the action of various", "action of various kinases", "of various kinases and", "various kinases and phosphatases", "kinases and phosphatases whilst", "and phosphatases whilst pi", "phosphatases whilst pi 4", "whilst pi 4 5", "4 5 p2 is", "5 p2 is also", "p2 is also a", "is also a substrate", "also a substrate for", "a substrate for phospholipase", "substrate for phospholipase c.", "for phospholipase c. the", "phospholipase c. the differential", "c. the differential localisation", "the differential localisation of", "differential localisation of each", "localisation of each of", "of each of these", "each of these enzymes", "of these enzymes on", "these enzymes on specific", "enzymes on specific compartment", "on specific compartment membranes", "specific compartment membranes ensures", "compartment membranes ensures maintenance", "membranes ensures maintenance of", "ensures maintenance of the", "maintenance of the heterogeneous", "of the heterogeneous distribution", "the heterogeneous distribution of", "heterogeneous distribution of phosphoinositides", "distribution of phosphoinositides despite", "of phosphoinositides despite the", "phosphoinositides despite the continuous", "despite the continuous membrane", "the continuous membrane flow", "continuous membrane flow from", "membrane flow from one", "flow from one compartment", "from one compartment to", "one compartment to another.

pi", "compartment to another.

pi is", "to another.

pi is primarily", "another.

pi is primarily synthesised", "is primarily synthesised in", "primarily synthesised in the", "synthesised in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum from", "endoplasmic reticulum from where", "reticulum from where the", "from where the phospholipid", "where the phospholipid is", "the phospholipid is exported", "phospholipid is exported to", "is exported to other", "exported to other compartments", "to other compartments via", "other compartments via membrane", "compartments via membrane traffic", "via membrane traffic or", "membrane traffic or via", "traffic or via cytosolic", "or via cytosolic phospholipid", "via cytosolic phospholipid transfer", "cytosolic phospholipid transfer proteins.", "phospholipid transfer proteins. phosphorylation", "transfer proteins. phosphorylation of", "proteins. phosphorylation of pi", "phosphorylation of pi to", "of pi to pi4p", "pi to pi4p primarily", "to pi4p primarily occurs", "pi4p primarily occurs in", "primarily occurs in the", "occurs in the golgi", "the golgi where", "golgi where pi4p", "where pi4p plays an", "pi4p plays an important", "plays an important role", "an important role in", "important role in the", "role in the biogenesis", "in the biogenesis of", "the biogenesis of transport", "biogenesis of transport vesicles", "of transport vesicles such", "transport vesicles such as", "vesicles such as the", "such as the secretory", "as the secretory vesicle", "the secretory vesicle involved", "secretory vesicle involved in", "vesicle involved in its", "involved in its transport", "in its transport to", "its transport to the", "transport to the plasma", "to the plasma membrane.", "the plasma membrane. at", "plasma membrane. at this", "membrane. at this place", "this place pi4p", "place pi4p has", "pi4p has a major", "has a major function", "a major function acting", "major function acting as", "function acting as a", "acting as a precursor", "as a precursor of", "a precursor of pi", "precursor of pi 4", "of pi 4 5", "5 p2 which", "p2 which is", "which is located predominantly", "is located predominantly at", "located predominantly at this", "predominantly at this membrane.", "at this membrane. pi", "this membrane. pi 4", "membrane. pi 4 5", "4 5 p2 binds", "5 p2 binds and", "p2 binds and regulates", "binds and regulates a", "and regulates a wide", "regulates a wide range", "a wide range of", "wide range of proteins", "range of proteins that", "of proteins that function", "proteins that function on", "that function on the", "function on the cell", "on the cell surface", "the cell surface and", "cell surface and serves", "surface and serves as", "and serves as a", "serves as a precursor", "as a precursor for", "a precursor for second", "precursor for second messengers.", "for second messengers. additionally", "messengers. additionally it", "additionally it helps", "it helps define this", "helps define this membrane", "define this membrane as", "this membrane as a", "membrane as a target", "as a target for", "a target for secretory", "target for secretory vesicles", "secretory vesicles functions", "vesicles functions as", "functions as a coreceptor", "as a coreceptor in", "a coreceptor in endocytic", "coreceptor in endocytic processes", "endocytic processes and", "processes and functions", "and functions as a", "functions as a cofactor", "as a cofactor for", "a cofactor for actin", "cofactor for actin nucleation.

at", "for actin nucleation.

at the", "actin nucleation.

at the plasma", "nucleation.

at the plasma membrane", "plasma membrane pi", "membrane pi 4", "5 p2 is further", "p2 is further phosphorylated", "is further phosphorylated to", "further phosphorylated to pi", "phosphorylated to pi 3", "to pi 3 4", "5 p3 another", "p3 another phosphoinositide", "another phosphoinositide with important", "phosphoinositide with important signalling", "with important signalling functions", "important signalling functions including", "signalling functions including stimulating", "functions including stimulating cell", "including stimulating cell survival", "stimulating cell survival and", "cell survival and proliferation.", "survival and proliferation. the", "and proliferation. the inositol", "proliferation. the inositol 3", "the inositol 3 phosphatase", "3 phosphatase phosphatase", "phosphatase phosphatase and", "phosphatase and tensin homolog", "tensin homolog pten", "pten regenerates pi", "regenerates pi 4 5", "5 p2 while", "p2 while the", "while the 5 phosphatases", "the 5 phosphatases convert", "5 phosphatases convert pi", "phosphatases convert pi 3", "convert pi 3 4", "4 5 p3 into", "5 p3 into the", "p3 into the phosphoinositide", "the phosphoinositide pi", "phosphoinositide pi 3", "4 p2 propagating", "p2 propagating the", "propagating the signal initiated", "the signal initiated by", "signal initiated by pi", "initiated by pi 3", "by pi 3 4", "3 4 5 p3.", "4 5 p3. pi", "5 p3. pi 3", "p3. pi 3 4", "3 4 p2 is", "4 p2 is further", "p2 is further dephosphorylated", "is further dephosphorylated in", "further dephosphorylated in the", "dephosphorylated in the endocytic", "in the endocytic pathway", "the endocytic pathway by", "endocytic pathway by inositol", "pathway by inositol 4", "by inositol 4 phosphatases", "inositol 4 phosphatases to", "4 phosphatases to pi3p", "to pi3p the", "pi3p the signature", "the signature phosphoinositide of", "signature phosphoinositide of the", "phosphoinositide of the early", "of the early endosomal", "the early endosomal compartment", "early endosomal compartment and", "endosomal compartment and a", "compartment and a ligand", "and a ligand for", "a ligand for numerous", "ligand for numerous endosomal", "for numerous endosomal proteins.", "numerous endosomal proteins. however", "proteins. however the", "however the bulk", "the bulk of pi3p", "bulk of pi3p is", "of pi3p is generated", "pi3p is generated directly", "is generated directly in", "generated directly in the", "directly in the endosomes", "in the endosomes by", "the endosomes by phosphorylation", "endosomes by phosphorylation of", "by phosphorylation of pi.", "phosphorylation of pi. the", "of pi. the subsequent", "pi. the subsequent endosomal", "the subsequent endosomal phosphorylation", "subsequent endosomal phosphorylation of", "endosomal phosphorylation of pi3p", "phosphorylation of pi3p to", "of pi3p to pi", "pi3p to pi 3", "to pi 3 5", "3 5 p2 is", "5 p2 is believed", "p2 is believed to", "is believed to generate", "believed to generate docking", "to generate docking sites", "generate docking sites for", "docking sites for recruitment", "sites for recruitment of", "for recruitment of cytosolic", "recruitment of cytosolic factors", "of cytosolic factors responsible", "cytosolic factors responsible for", "factors responsible for the", "responsible for the control", "for the control of", "the control of outgoing", "control of outgoing traffic", "of outgoing traffic from", "outgoing traffic from the", "traffic from the endosomes.", "from the endosomes. the", "the endosomes. the main", "endosomes. the main localisation", "the main localisation and", "main localisation and function", "localisation and function of", "and function of the", "function of the low", "of the low abundance", "the low abundance phosphoinositide", "low abundance phosphoinositide pi5p", "phosphoinositide pi5p that", "pi5p that can", "that can be generated", "can be generated by", "be generated by several", "generated by several pathways", "several pathways remains", "pathways remains to", "remains to be determined", "be determined krauss", "determined krauss &", "krauss & haucke 2007", "haucke 2007 leventis", "2007 leventis &", "leventis & grinstein 2010", "grinstein 2010 roth", "2010 roth 2004", "roth 2004 gees", "2004 gees et", "gees et al. 2010", "al. 2010 de", "2010 de matteis", "de matteis & godi", "matteis & godi 2004", "godi 2004 van", "2004 van meer", "van meer et al.", "meer et al. 2008", "al. 2008 vicinanza", "2008 vicinanza et", "vicinanza et al. 2008", "al. 2008 lemmon", "2008 lemmon 2008", "lemmon 2008 kutaleladze", "2008 kutaleladze 2010", "kutaleladze 2010 robinson", "2010 robinson &", "robinson & dixon 2006", "dixon 2006 blero", "2006 blero et", "blero et al. 2007", "al. 2007 liu", "2007 liu &", "liu & bankaitis 2010", "bankaitis 2010 mccrea", "2010 mccrea &", "mccrea & de camilli", "& de camilli 2009", "camilli 2009 vicinanza", "2009 vicinanza et", "al. 2008 di", "2008 di paolo", "di paolo & de", "paolo & de camilli", "de camilli 2006", "camilli 2006 .", "pi a membrane", "a membrane phospholipid can", "membrane phospholipid can be", "phospholipid can be reversibly", "can be reversibly phosphorylated at", "be reversibly phosphorylated at the", "reversibly phosphorylated at the 3", "at the 3 4", "3 4 and", "4 and 5 positions", "and 5 positions of the", "5 positions of the inositol", "positions of the inositol ring", "of the inositol ring to", "the inositol ring to generate", "inositol ring to generate seven", "ring to generate seven phosphoinositides:", "to generate seven phosphoinositides: phosphatidylinositol", "generate seven phosphoinositides: phosphatidylinositol 3", "seven phosphoinositides: phosphatidylinositol 3 phosphate", "phosphatidylinositol 3 phosphate pi3p", "pi3p phosphatidylinositol 4", "phosphatidylinositol 4 phosphate pi4p", "pi4p phosphatidylinositol 5", "phosphatidylinositol 5 phosphate pi5p", "pi5p phosphatidylinositol 3", "phosphatidylinositol 3 4 bisphosphate pi", "3 4 bisphosphate pi 3", "4 bisphosphate pi 3 4", "bisphosphate pi 3 4 p2", "3 4 p2 phosphatidylinositol", "4 p2 phosphatidylinositol 4", "p2 phosphatidylinositol 4 5", "phosphatidylinositol 4 5 bisphosphate pi", "4 5 bisphosphate pi 4", "5 bisphosphate pi 4 5", "bisphosphate pi 4 5 p2", "4 5 p2 phosphatidylinositol", "5 p2 phosphatidylinositol 3", "p2 phosphatidylinositol 3 5", "phosphatidylinositol 3 5 bisphosphate pi", "3 5 bisphosphate pi 3", "5 bisphosphate pi 3 5", "bisphosphate pi 3 5 p2", "3 5 p2 and", "5 p2 and phosphatidylinositol", "p2 and phosphatidylinositol 3", "and phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "4 5 trisphosphate pi", "5 trisphosphate pi 3", "trisphosphate pi 3 4", "pi 3 4 5 p3", "3 4 5 p3 .", "4 5 p3 . these", "5 p3 . these seven", "p3 . these seven phosphoinositides", "these seven phosphoinositides which", "seven phosphoinositides which are", "phosphoinositides which are heterogeneously", "which are heterogeneously distributed within", "are heterogeneously distributed within cells", "distributed within cells can", "within cells can serve", "cells can serve as", "can serve as signature components", "serve as signature components of", "as signature components of different", "signature components of different intracellular", "components of different intracellular compartment", "of different intracellular compartment membranes", "different intracellular compartment membranes and", "intracellular compartment membranes and so", "compartment membranes and so help", "membranes and so help to", "and so help to mediate", "so help to mediate specificity", "help to mediate specificity of", "to mediate specificity of membrane", "mediate specificity of membrane interactions.", "specificity of membrane interactions. phosphoinositide", "of membrane interactions. phosphoinositide levels", "membrane interactions. phosphoinositide levels are", "interactions. phosphoinositide levels are tightly", "phosphoinositide levels are tightly regulated", "levels are tightly regulated spatially", "are tightly regulated spatially and", "tightly regulated spatially and temporally", "regulated spatially and temporally by", "spatially and temporally by the", "and temporally by the action", "temporally by the action of", "by the action of various", "the action of various kinases", "action of various kinases and", "of various kinases and phosphatases", "various kinases and phosphatases whilst", "kinases and phosphatases whilst pi", "and phosphatases whilst pi 4", "phosphatases whilst pi 4 5", "whilst pi 4 5 p2", "pi 4 5 p2 is", "4 5 p2 is also", "5 p2 is also a", "p2 is also a substrate", "is also a substrate for", "also a substrate for phospholipase", "a substrate for phospholipase c.", "substrate for phospholipase c. the", "for phospholipase c. the differential", "phospholipase c. the differential localisation", "c. the differential localisation of", "the differential localisation of each", "differential localisation of each of", "localisation of each of these", "of each of these enzymes", "each of these enzymes on", "of these enzymes on specific", "these enzymes on specific compartment", "enzymes on specific compartment membranes", "on specific compartment membranes ensures", "specific compartment membranes ensures maintenance", "compartment membranes ensures maintenance of", "membranes ensures maintenance of the", "ensures maintenance of the heterogeneous", "maintenance of the heterogeneous distribution", "of the heterogeneous distribution of", "the heterogeneous distribution of phosphoinositides", "heterogeneous distribution of phosphoinositides despite", "distribution of phosphoinositides despite the", "of phosphoinositides despite the continuous", "phosphoinositides despite the continuous membrane", "despite the continuous membrane flow", "the continuous membrane flow from", "continuous membrane flow from one", "membrane flow from one compartment", "flow from one compartment to", "from one compartment to another.

pi", "one compartment to another.

pi is", "compartment to another.

pi is primarily", "to another.

pi is primarily synthesised", "another.

pi is primarily synthesised in", "is primarily synthesised in the", "primarily synthesised in the endoplasmic", "synthesised in the endoplasmic reticulum", "in the endoplasmic reticulum from", "the endoplasmic reticulum from where", "endoplasmic reticulum from where the", "reticulum from where the phospholipid", "from where the phospholipid is", "where the phospholipid is exported", "the phospholipid is exported to", "phospholipid is exported to other", "is exported to other compartments", "exported to other compartments via", "to other compartments via membrane", "other compartments via membrane traffic", "compartments via membrane traffic or", "via membrane traffic or via", "membrane traffic or via cytosolic", "traffic or via cytosolic phospholipid", "or via cytosolic phospholipid transfer", "via cytosolic phospholipid transfer proteins.", "cytosolic phospholipid transfer proteins. phosphorylation", "phospholipid transfer proteins. phosphorylation of", "transfer proteins. phosphorylation of pi", "proteins. phosphorylation of pi to", "phosphorylation of pi to pi4p", "of pi to pi4p primarily", "pi to pi4p primarily occurs", "to pi4p primarily occurs in", "pi4p primarily occurs in the", "primarily occurs in the golgi", "in the golgi where", "the golgi where pi4p", "golgi where pi4p plays", "where pi4p plays an important", "pi4p plays an important role", "plays an important role in", "an important role in the", "important role in the biogenesis", "role in the biogenesis of", "in the biogenesis of transport", "the biogenesis of transport vesicles", "biogenesis of transport vesicles such", "of transport vesicles such as", "transport vesicles such as the", "vesicles such as the secretory", "such as the secretory vesicle", "as the secretory vesicle involved", "the secretory vesicle involved in", "secretory vesicle involved in its", "vesicle involved in its transport", "involved in its transport to", "in its transport to the", "its transport to the plasma", "transport to the plasma membrane.", "to the plasma membrane. at", "the plasma membrane. at this", "plasma membrane. at this place", "at this place pi4p", "this place pi4p has", "place pi4p has a", "pi4p has a major function", "has a major function acting", "a major function acting as", "major function acting as a", "function acting as a precursor", "acting as a precursor of", "as a precursor of pi", "a precursor of pi 4", "precursor of pi 4 5", "of pi 4 5 p2", "4 5 p2 which", "5 p2 which is", "p2 which is located", "which is located predominantly at", "is located predominantly at this", "located predominantly at this membrane.", "predominantly at this membrane. pi", "at this membrane. pi 4", "this membrane. pi 4 5", "membrane. pi 4 5 p2", "pi 4 5 p2 binds", "4 5 p2 binds and", "5 p2 binds and regulates", "p2 binds and regulates a", "binds and regulates a wide", "and regulates a wide range", "regulates a wide range of", "a wide range of proteins", "wide range of proteins that", "range of proteins that function", "of proteins that function on", "proteins that function on the", "that function on the cell", "function on the cell surface", "on the cell surface and", "the cell surface and serves", "cell surface and serves as", "surface and serves as a", "and serves as a precursor", "serves as a precursor for", "as a precursor for second", "a precursor for second messengers.", "precursor for second messengers. additionally", "second messengers. additionally it", "messengers. additionally it helps", "additionally it helps define", "it helps define this membrane", "helps define this membrane as", "define this membrane as a", "this membrane as a target", "membrane as a target for", "as a target for secretory", "a target for secretory vesicles", "for secretory vesicles functions", "secretory vesicles functions as", "vesicles functions as a", "functions as a coreceptor in", "as a coreceptor in endocytic", "a coreceptor in endocytic processes", "in endocytic processes and", "endocytic processes and functions", "processes and functions as", "and functions as a cofactor", "functions as a cofactor for", "as a cofactor for actin", "a cofactor for actin nucleation.

at", "cofactor for actin nucleation.

at the", "for actin nucleation.

at the plasma", "actin nucleation.

at the plasma membrane", "the plasma membrane pi", "plasma membrane pi 4", "membrane pi 4 5", "4 5 p2 is further", "5 p2 is further phosphorylated", "p2 is further phosphorylated to", "is further phosphorylated to pi", "further phosphorylated to pi 3", "phosphorylated to pi 3 4", "to pi 3 4 5", "4 5 p3 another", "5 p3 another phosphoinositide", "p3 another phosphoinositide with", "another phosphoinositide with important signalling", "phosphoinositide with important signalling functions", "with important signalling functions including", "important signalling functions including stimulating", "signalling functions including stimulating cell", "functions including stimulating cell survival", "including stimulating cell survival and", "stimulating cell survival and proliferation.", "cell survival and proliferation. the", "survival and proliferation. the inositol", "and proliferation. the inositol 3", "proliferation. the inositol 3 phosphatase", "inositol 3 phosphatase phosphatase", "3 phosphatase phosphatase and", "phosphatase phosphatase and tensin", "and tensin homolog pten", "homolog pten regenerates", "pten regenerates pi 4", "regenerates pi 4 5 p2", "4 5 p2 while", "5 p2 while the", "p2 while the 5", "while the 5 phosphatases convert", "the 5 phosphatases convert pi", "5 phosphatases convert pi 3", "phosphatases convert pi 3 4", "convert pi 3 4 5", "3 4 5 p3 into", "4 5 p3 into the", "5 p3 into the phosphoinositide", "into the phosphoinositide pi", "the phosphoinositide pi 3", "phosphoinositide pi 3 4", "3 4 p2 propagating", "4 p2 propagating the", "p2 propagating the signal", "propagating the signal initiated by", "the signal initiated by pi", "signal initiated by pi 3", "initiated by pi 3 4", "by pi 3 4 5", "pi 3 4 5 p3.", "3 4 5 p3. pi", "4 5 p3. pi 3", "5 p3. pi 3 4", "p3. pi 3 4 p2", "pi 3 4 p2 is", "3 4 p2 is further", "4 p2 is further dephosphorylated", "p2 is further dephosphorylated in", "is further dephosphorylated in the", "further dephosphorylated in the endocytic", "dephosphorylated in the endocytic pathway", "in the endocytic pathway by", "the endocytic pathway by inositol", "endocytic pathway by inositol 4", "pathway by inositol 4 phosphatases", "by inositol 4 phosphatases to", "inositol 4 phosphatases to pi3p", "phosphatases to pi3p the", "to pi3p the signature", "pi3p the signature phosphoinositide", "the signature phosphoinositide of the", "signature phosphoinositide of the early", "phosphoinositide of the early endosomal", "of the early endosomal compartment", "the early endosomal compartment and", "early endosomal compartment and a", "endosomal compartment and a ligand", "compartment and a ligand for", "and a ligand for numerous", "a ligand for numerous endosomal", "ligand for numerous endosomal proteins.", "for numerous endosomal proteins. however", "endosomal proteins. however the", "proteins. however the bulk", "however the bulk of", "the bulk of pi3p is", "bulk of pi3p is generated", "of pi3p is generated directly", "pi3p is generated directly in", "is generated directly in the", "generated directly in the endosomes", "directly in the endosomes by", "in the endosomes by phosphorylation", "the endosomes by phosphorylation of", "endosomes by phosphorylation of pi.", "by phosphorylation of pi. the", "phosphorylation of pi. the subsequent", "of pi. the subsequent endosomal", "pi. the subsequent endosomal phosphorylation", "the subsequent endosomal phosphorylation of", "subsequent endosomal phosphorylation of pi3p", "endosomal phosphorylation of pi3p to", "phosphorylation of pi3p to pi", "of pi3p to pi 3", "pi3p to pi 3 5", "to pi 3 5 p2", "pi 3 5 p2 is", "3 5 p2 is believed", "5 p2 is believed to", "p2 is believed to generate", "is believed to generate docking", "believed to generate docking sites", "to generate docking sites for", "generate docking sites for recruitment", "docking sites for recruitment of", "sites for recruitment of cytosolic", "for recruitment of cytosolic factors", "recruitment of cytosolic factors responsible", "of cytosolic factors responsible for", "cytosolic factors responsible for the", "factors responsible for the control", "responsible for the control of", "for the control of outgoing", "the control of outgoing traffic", "control of outgoing traffic from", "of outgoing traffic from the", "outgoing traffic from the endosomes.", "traffic from the endosomes. the", "from the endosomes. the main", "the endosomes. the main localisation", "endosomes. the main localisation and", "the main localisation and function", "main localisation and function of", "localisation and function of the", "and function of the low", "function of the low abundance", "of the low abundance phosphoinositide", "the low abundance phosphoinositide pi5p", "abundance phosphoinositide pi5p that", "phosphoinositide pi5p that can", "pi5p that can be", "that can be generated by", "can be generated by several", "be generated by several pathways", "by several pathways remains", "several pathways remains to", "pathways remains to be", "to be determined krauss", "be determined krauss &", "determined krauss & haucke", "& haucke 2007 leventis", "haucke 2007 leventis &", "2007 leventis & grinstein", "& grinstein 2010 roth", "grinstein 2010 roth 2004", "roth 2004 gees et", "2004 gees et al.", "et al. 2010 de", "al. 2010 de matteis", "2010 de matteis &", "de matteis & godi 2004", "& godi 2004 van", "godi 2004 van meer", "2004 van meer et", "van meer et al. 2008", "et al. 2008 vicinanza", "al. 2008 vicinanza et", "2008 vicinanza et al.", "et al. 2008 lemmon", "al. 2008 lemmon 2008", "lemmon 2008 kutaleladze 2010", "kutaleladze 2010 robinson &", "2010 robinson & dixon", "& dixon 2006 blero", "dixon 2006 blero et", "2006 blero et al.", "et al. 2007 liu", "al. 2007 liu &", "2007 liu & bankaitis", "& bankaitis 2010 mccrea", "bankaitis 2010 mccrea &", "2010 mccrea & de", "mccrea & de camilli 2009", "de camilli 2009 vicinanza", "camilli 2009 vicinanza et", "2009 vicinanza et al.", "et al. 2008 di", "al. 2008 di paolo", "2008 di paolo &", "di paolo & de camilli", "& de camilli 2006", "de camilli 2006 ." ] }, { "record_id": "GLY_000594_1_773", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1489509", "r hsa", "hsa 1489509", "r hsa 1489509" ] }, { "record_id": "GLY_000594_1_773", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dag and", "and ip3", "ip3 signaling", "dag and ip3", "and ip3 signaling", "dag and ip3 signaling", "this pathway", "pathway describes", "describes the", "the generation", "generation of", "of dag", "ip3 by", "by the", "the plcgamma", "plcgamma mediated", "mediated hydrolysis", "hydrolysis of", "of pip2", "pip2 and", "and the", "the subsequent", "subsequent downstream", "downstream signaling", "signaling events.", "this pathway describes", "pathway describes the", "describes the generation", "the generation of", "generation of dag", "of dag and", "and ip3 by", 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since been shown", "since been shown to", "been shown to be", "shown to be an", "to be an important", "be an important participant", "an important participant in", "important participant in the", "participant in the differentiation", "in the differentiation of", "the differentiation of embryonic", "differentiation of embryonic cells", "of embryonic cells into", "embryonic cells into mesodermal", "cells into mesodermal and", "into mesodermal and endodermal", "mesodermal and endodermal layers.", "and endodermal layers. activin", "endodermal layers. activin binds", "layers. activin binds the", "activin binds the activin", "binds the activin receptor", "the activin receptor and", "activin receptor and triggers", "receptor and triggers downstream", "and triggers downstream events:", "triggers downstream events: phosphorylation", "downstream events: phosphorylation of", "events: phosphorylation of smad2", "phosphorylation of smad2 and", "of smad2 and smad3", "smad2 and smad3 followed", "and smad3 followed by", "smad3 followed by activation", "followed by activation of", "by activation of gene", "activation of gene expression", "gene expression reviewed", "expression reviewed in", "reviewed in attisano et", "in attisano et al.", "attisano et al. 1996", "al. 1996 willis", "1996 willis et", "willis et al. 1996", "al. 1996 chen", "1996 chen et", "chen et al. 2006", "al. 2006 hinck", "2006 hinck 2012", "2012 . activins", ". activins are", "activins are dimers comprising", "are dimers comprising activin", "dimers comprising activin a", "activin a inhba:inhba", "inhba:inhba activin", "activin ab inhba:inhbb", "inhba:inhbb and", "activin b inhbb:inhbb", "b inhbb:inhbb .", "inhbb:inhbb . activin first", ". activin first binds", "activin first binds the", "first binds the type", "binds the type ii", "the type ii receptor", "ii receptor acvr2a", "acvr2b and this", "and this complex then", "this complex then interacts", "complex then interacts with", "then interacts with the", 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complex enters", "ternary complex enters the", "complex enters the nucleus", "enters the nucleus and", "the nucleus and activates", "nucleus and activates target", "and activates target genes.", "activin was initially discovered as", "was initially discovered as an", "initially discovered as an activator", "discovered as an activator of", "as an activator of follicle", "an activator of follicle stimulating", "activator of follicle stimulating hormone", "of follicle stimulating hormone in", "follicle stimulating hormone in the", "stimulating hormone in the pituitary", "hormone in the pituitary gland.", "in the pituitary gland. it", "the pituitary gland. it has", "pituitary gland. it has since", "gland. it has since been", "it has since been shown", "has since been shown to", "since been shown to be", "been shown to be an", "shown to be an important", "to be an important participant", "be an important participant in", "an important participant in the", "important participant in the differentiation", "participant in the differentiation of", "in the differentiation of embryonic", "the differentiation of embryonic cells", "differentiation of embryonic cells into", "of embryonic cells into mesodermal", "embryonic cells into mesodermal and", "cells into mesodermal and endodermal", "into mesodermal and endodermal layers.", "mesodermal and endodermal layers. activin", "and endodermal layers. activin binds", "endodermal layers. activin binds the", "layers. activin binds the activin", "activin binds the activin receptor", "binds the activin receptor and", "the activin receptor and triggers", "activin receptor and triggers downstream", "receptor and triggers downstream events:", "and triggers downstream events: phosphorylation", "triggers downstream events: phosphorylation of", "downstream events: phosphorylation of smad2", "events: phosphorylation of smad2 and", "phosphorylation of smad2 and smad3", "of smad2 and smad3 followed", "smad2 and smad3 followed by", "and smad3 followed by activation", "smad3 followed by activation of", "followed by activation of gene", "by activation of gene expression", "of gene expression reviewed", "gene expression reviewed in", "expression reviewed in attisano", "reviewed in attisano et al.", "in attisano et al. 1996", "et al. 1996 willis", "al. 1996 willis et", "1996 willis et al.", "et al. 1996 chen", "al. 1996 chen et", "1996 chen et al.", "et al. 2006 hinck", "al. 2006 hinck 2012", "2006 hinck 2012 .", "hinck 2012 . activins", "2012 . activins are", ". activins are dimers", "activins are dimers comprising activin", "are dimers comprising activin a", "comprising activin a inhba:inhba", "inhba:inhba activin ab", "inhba:inhbb and activin", "and activin b inhbb:inhbb", "activin b inhbb:inhbb .", "b inhbb:inhbb . activin", "inhbb:inhbb . activin first binds", ". activin first binds the", "activin first binds the type", "first binds the type ii", "binds the type ii receptor", "type ii receptor acvr2a", "receptor acvr2a acvr2b", "acvr2a acvr2b and", "acvr2b and this complex", "and this complex then interacts", "this complex then interacts with", "complex then interacts with the", "then interacts with the type", "interacts with the type i", "with the type i receptor", "type i receptor acvr1b", "receptor acvr1b acvr1c", "acvr1c attisano et", "attisano et al. 1996 .", "et al. 1996 . the", "al. 1996 . the type", "1996 . the type ii", ". the type ii receptor", "the type ii receptor phosphorylates", "type ii receptor phosphorylates the", "ii receptor phosphorylates the type", "receptor phosphorylates the type i", "phosphorylates the type i receptor", "the type i receptor and", "type i receptor and then", "i receptor and then the", "receptor and then the phosphorylated", "and then the phosphorylated type", "then the phosphorylated type i", "the phosphorylated type i receptor", "phosphorylated type i receptor phosphorylates", "type i receptor phosphorylates smad2", "i receptor phosphorylates smad2 and", "receptor phosphorylates smad2 and smad3.", "phosphorylates smad2 and smad3. dimers", "smad2 and smad3. dimers of", "and smad3. dimers of phosphorylated", "smad3. dimers of phosphorylated smad2/3", "dimers of phosphorylated smad2/3 bind", "of phosphorylated smad2/3 bind smad4", "phosphorylated smad2/3 bind smad4 and", "smad2/3 bind smad4 and the", "bind smad4 and the resulting", "smad4 and the resulting ternary", "and the resulting ternary complex", "the resulting ternary complex enters", "resulting ternary complex enters the", "ternary complex enters the nucleus", "complex enters the nucleus and", "enters the nucleus and activates", "the nucleus and activates target", "nucleus and activates target genes." ] }, { "record_id": "GLY_000594_1_775", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1538133", "r hsa", "hsa 1538133", "r hsa 1538133" ] }, { "record_id": "GLY_000594_1_775", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "g0 and", "and early", "early g1", "g0 and early", "and early g1", "g0 and early g1", "in g0", "g1 in", "in quiescent", "quiescent cells", "bound to", "to e2f4", "e2f4 or", "or e2f5", "e2f5 and", "and either", "either dp1", "dp1 or", "or dp2", "associates with", "with the", "the muvb", "muvb complex", "forming an", "an evolutionarily", "evolutionarily conserved", "conserved dream", "dream complex", "that represses", "represses transcription", "transcription of", "of cell", "cell cycle", "cycle genes.", "genes. during", "during early", "g1 phase", "phase in", "in actively", "actively cycling", "cycling cells", "forms a", "a complex", "complex with", "with e2f4", "e2f4 and", "and dp1", "dp2 and", "and represses", "of e2f", "e2f target", "target genes.", "genes. both", "both p130", "and p107", "repress transcription", "e2f targets", "targets through", "through recruiting", "recruiting histone", "histone deacetylase", "deacetylase hdac1", "possibly in", "in complex", "with other", "other chromatin", "chromatin modifying", "modifying enzymes", "to e2f", "e2f regulated", "regulated promoters.", "promoters. expression", "expression of", "of p107", "is cell", "cycle regulated", "with its", "its levels", "levels peaking", "peaking in", "in late", "late g1", "g1 and", "and s", "s phase.", "phase. although", "although p107", "is phosphorylated", "phosphorylated by", "by cyclin", "cyclin d", "d assocaited", "assocaited kinases", "kinases during", "during late", "a small", "small pool", "pool of", "is thought", "thought to", "to be", "be present", "present throughout", "throughout g1", "s phase", "and could", "could be", "be involved", "involved in", "in fine", "fine tuning", "tuning the", "the transcription", "of s", "phase genes.", "genes. this", "this is", "is supported", "supported by", "by studies", "studies showing", "showing that", "that unlike", "unlike rb1", "rb1 and", "and p130", "which are", "are able", "able to", "to induce", 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"represses transcription of", "transcription of cell", "of cell cycle", "cell cycle genes.", "cycle genes. during", "genes. during early", "during early g1", "early g1 phase", "g1 phase in", "phase in actively", "in actively cycling", "actively cycling cells", "cells p107", "p107 rbl1", "rbl1 forms", "forms a complex", "a complex with", "complex with e2f4", "with e2f4 and", "e2f4 and dp1", "and dp1 or", "or dp2 and", "dp2 and represses", "and represses transcription", "transcription of e2f", "of e2f target", "e2f target genes.", "target genes. both", "genes. both p130", "rbl2 and", "rbl1 repress", "repress transcription of", "of e2f targets", "e2f targets through", "targets through recruiting", "through recruiting histone", "recruiting histone deacetylase", "histone deacetylase hdac1", "hdac1 possibly", "possibly in complex", "in complex with", "complex with other", "with other chromatin", "other chromatin modifying", "chromatin modifying enzymes", "enzymes to", "to e2f regulated", "e2f regulated promoters.", "regulated promoters. expression", "promoters. expression of", "expression of p107", "rbl1 is", "is cell cycle", "cell cycle regulated", "regulated with", "with its levels", "its levels peaking", "levels peaking in", "peaking in late", "in late g1", "late g1 and", "g1 and s", "and s phase.", "s phase. although", "phase. although p107", "is phosphorylated by", "phosphorylated by cyclin", "by cyclin d", "cyclin d assocaited", "d assocaited kinases", "assocaited kinases during", "kinases during late", "during late g1", "late g1 phase", "phase a", "a small pool", "small pool of", "pool of p107", "is thought to", "thought to be", "to be present", "be present throughout", "present throughout g1", "throughout g1 and", "and s phase", "phase and", "and could be", "could be involved", "be involved in", "involved in fine", "in fine tuning", "fine tuning the", "tuning the transcription", "the transcription of", "transcription of s", "of s phase", "s phase genes.", 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cobrinik 2005.", "in g0 and early", "and early g1 in", "early g1 in quiescent", "g1 in quiescent cells", "quiescent cells p130", "rbl2 bound to", "bound to e2f4 or", "to e2f4 or e2f5", "e2f4 or e2f5 and", "or e2f5 and either", "e2f5 and either dp1", "and either dp1 or", "either dp1 or dp2", "or dp2 associates", "dp2 associates with", "associates with the muvb", "with the muvb complex", "muvb complex forming", "complex forming an", "forming an evolutionarily conserved", "an evolutionarily conserved dream", "evolutionarily conserved dream complex", "dream complex that", "complex that represses", "that represses transcription of", "represses transcription of cell", "transcription of cell cycle", "of cell cycle genes.", "cell cycle genes. during", "cycle genes. during early", "genes. during early g1", "during early g1 phase", "early g1 phase in", "g1 phase in actively", "phase in actively cycling", "in actively cycling cells", "cycling cells p107", "rbl1 forms a", "forms a complex with", "a complex with e2f4", "complex with e2f4 and", "with e2f4 and dp1", "e2f4 and dp1 or", "and dp1 or dp2", "dp1 or dp2 and", "or dp2 and represses", "dp2 and represses transcription", "and represses transcription of", "represses transcription of e2f", "transcription of e2f target", "of e2f target genes.", "e2f target genes. both", "target genes. both p130", "both p130 rbl2", "rbl2 and p107", "and p107 rbl1", "rbl1 repress transcription", "repress transcription of e2f", "transcription of e2f targets", "of e2f targets through", "e2f targets through recruiting", "targets through recruiting histone", "through recruiting histone deacetylase", "recruiting histone deacetylase hdac1", "deacetylase hdac1 possibly", "hdac1 possibly in", "possibly in complex with", "in complex with other", "complex with other chromatin", "with other chromatin modifying", "other chromatin modifying enzymes", "modifying enzymes to", "enzymes to e2f", "to e2f regulated promoters.", "e2f regulated promoters. expression", "regulated promoters. expression of", "promoters. expression of p107", "of p107 rbl1", "rbl1 is cell", "is cell cycle regulated", "cycle regulated with", "regulated with its", "with its levels peaking", "its levels peaking in", "levels peaking in late", "peaking in late g1", "in late g1 and", "late g1 and s", "g1 and s phase.", "and s phase. although", "s phase. although p107", "although p107 rbl1", "rbl1 is phosphorylated", "is phosphorylated by cyclin", "phosphorylated by cyclin d", "by cyclin d assocaited", "cyclin d assocaited kinases", "d assocaited kinases during", "assocaited kinases during late", "kinases during late g1", "during late g1 phase", "g1 phase a", "phase a small", "a small pool of", "small pool of p107", "rbl1 is thought", "is thought to be", "thought to be present", "to be present throughout", "be present throughout g1", "present throughout g1 and", "throughout g1 and s", "g1 and s phase", "s phase and", "phase and could", "and could be involved", 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the", "expression can arrest the cell", "can arrest the cell cycle", "arrest the cell cycle in", "the cell cycle in both", "cell cycle in both g1", "cycle in both g1 and", "in both g1 and s", "both g1 and s phase.", "g1 and s phase. for", "and s phase. for recent", "s phase. for recent reviews", "phase. for recent reviews on", "for recent reviews on the", "recent reviews on the function", "reviews on the function of", "on the function of p107", "function of p107 p130", "of p107 p130 and", "p107 p130 and pocket", "p130 and pocket proteins in", "and pocket proteins in general", "proteins in general please", "in general please refer", "general please refer to", "please refer to wirt and", "refer to wirt and sage", "wirt and sage 2010", "sage 2010 macpherson", "2010 macpherson 2008 and", "macpherson 2008 and cobrinik 2005." ] }, { "record_id": "GLY_000594_1_776", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "156588", "r hsa", "hsa 156588", "r hsa 156588" ] }, { "record_id": "GLY_000594_1_776", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glucuronidation conjugation", "conjugation utilizes", "utilizes udp", "udp glucuronosyltransferases", "ec 2.4.1.17", "to catalyze", "catalyze a", "a wide", "wide range", "range of", "of diverse", "diverse endogenous", "endogenous and", "and xenobiotic", "xenobiotic compounds.", "compounds. glucuronidation", "glucuronidation is", "is the", "the major", "major pathway", "pathway in", "in phase", "phase ii", "ii metabolism", "metabolism and", "and accounts", "accounts for", "for approximately", "approximately 35%", "35% of", "of drug", "drug conjugation.", "conjugation. ugts", "ugts are", "are microsomal", "microsomal membrane", "membrane bound", "bound and", "and catalyze", "catalyze the", "the transfer", "transfer of", "of a", "a glucuronate", "glucuronate group", "group of", "of uridine", "uridine diphosphoglucuronate", "a co", "co substrate", "to the", "the functional", "functional group", "of specific", "specific substrates.", "substrates. udpga", "udpga is", "is synthesized", "synthesized from", "from glucose", "glucose 1", "1 phosphate", "g1p .", ". g1p", "g1p is", "is required", "required for", "for glycolysis", "glycolysis and", "and is", "is present", "present in", "in high", "high concentrations", "concentrations in", "in the", "the cell", "making it", "it is", "is unlikely", "unlikely to", "to be", "be a", "a limiting", "limiting factor", "factor in", "in udpga", "udpga synthesis.", "synthesis. udp", "udp is", "is added", "added to", "to g1p", "g1p to", "to form", "form udp", "udp glucose", "glucose which", "which is", "is then", "then dehydrogenated", "dehydrogenated to", "form udpga.", "udpga. the", "the basic", "basic reaction", "reaction is

udp", "is

udp glucuronate", "glucuronate +", "+ acceptor", "> udp", "udp +", "acceptor beta", "beta d", "d glucuronide

the", "glucuronide

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the", "57kda.
the ugt1", "ugt1 family", "family comprises", "comprises of", "of 9", "9 proteins", "1a3 1a10", "but only", "only 5", "5 have", "have been", "been isolated", "isolated in", "in humans.", "humans. example", "example substrates", "substrates which", "are glucuronidated", "glucuronidated are", "are acetaminophen", "acetaminophen by", "by ugt1a6", "ugt1a6 and", "and bilirubin", "bilirubin by", "by ugt1a1.", "ugt1a1. members", "members of", "of the", "the ugt2", "ugt2 subfamily", "subfamily are", "are each", "each encoded", "encoded by", "by their", "their own", "own genes", "in contrast", "contrast to", "to ugt1as", "ugt1as which", "are encoded", "encoded at", "at the", "the ugt1", "ugt1 locus.", "locus. example", "substrates are", "are morphine", "morphine conjugation", "conjugation by", "by ugt2b7", "ugt2b7 and", "and androgenic", "androgenic steroid", "steroid conjugation", "by ugt2b17.
xenobiotics", "ugt2b17.
xenobiotics conjugated", "conjugated with", "with glucuronic", "glucuronic acid", "acid can", "can be", "be substrates", "substrates for", "for beta", "beta glucuronidase", "an enzyme", "enzyme common", "common in", "in gut", "gut microflora.", "microflora. this", "this enzyme", "enzyme can", "can release", "release the", "the parent", "parent or", "or phase", "phase i", "i metabolite", "metabolite which", "be reabsorbed.", "reabsorbed. it", "it can", "then either", "either re", "re exert", "exert it's", "it's original", "original effects", "effects or", "or be", "be conjugated", "conjugated by", "by glucuronic", "acid again.", "again. this", "this cycle", "cycle is", "is called", "called enterohepatic", "enterohepatic circulation", "circulation and", "and can", "can delay", "delay the", "the elimination", "elimination of", "the xenobiotic.", "glucuronidation conjugation utilizes", "conjugation utilizes udp", "utilizes udp glucuronosyltransferases", "glucuronosyltransferases ugts", "ugts ec", "2.4.1.17 to", "to catalyze a", "catalyze a wide", "a wide range", "wide range of", "range of diverse", "of diverse endogenous", "diverse endogenous and", "endogenous and xenobiotic", "and xenobiotic compounds.", "xenobiotic compounds. glucuronidation", "compounds. glucuronidation is", "glucuronidation is the", "is the major", "the major pathway", "major pathway in", "pathway in phase", "in phase ii", "phase ii metabolism", "ii metabolism and", "metabolism and accounts", "and accounts for", "accounts for approximately", "for approximately 35%", "approximately 35% of", "35% of drug", "of drug conjugation.", "drug conjugation. ugts", "conjugation. ugts are", "ugts are microsomal", "are microsomal membrane", "microsomal membrane bound", "membrane bound and", "bound and catalyze", "and catalyze the", "catalyze the transfer", "the transfer of", "transfer of a", "of a glucuronate", "a glucuronate group", "glucuronate group of", "group of uridine", "of uridine diphosphoglucuronate", "diphosphoglucuronate udpga", "udpga a", "a co substrate", "substrate to", "to the functional", "the functional group", "functional group of", "group of specific", "of specific substrates.", "specific substrates. udpga", "substrates. udpga is", "udpga is synthesized", "is synthesized from", "synthesized from glucose", "from glucose 1", "glucose 1 phosphate", "phosphate g1p", "g1p . g1p", ". g1p is", "g1p is required", "is required for", "required for glycolysis", "for glycolysis and", "glycolysis and is", "and is present", "is present in", "present in high", "in high concentrations", "high concentrations in", "concentrations in the", "in the cell", "cell making", "making it is", "it is unlikely", "is unlikely to", "unlikely to be", "to be a", "be a limiting", "a limiting factor", "limiting factor in", "factor in udpga", "in udpga synthesis.", "udpga synthesis. udp", "synthesis. udp is", "udp is added", "is added to", "added to g1p", "to g1p to", "g1p to form", "to form udp", "form udp glucose", "udp glucose which", "glucose which is", "which is then", "is then dehydrogenated", "then dehydrogenated to", "dehydrogenated to form", "to form udpga.", "form udpga. the", "udpga. the basic", "the basic reaction", "basic reaction is

udp", "reaction is

udp glucuronate", "is

udp glucuronate +", "glucuronate + acceptor", "acceptor >", "> udp +", "udp + acceptor", "+ acceptor beta", "acceptor beta d", "beta d glucuronide

the", "d glucuronide

the effect", "glucuronide

the effect of", "effect of this", "of this conjugation", "this conjugation is", "conjugation is to", "is to confer", "to confer polarity", "confer polarity to", "polarity to the", "to the substrate", "the substrate which", "substrate which can", "which can then", "can then be", "then be easily", "be easily excreted", "easily excreted in", "excreted in urine", "in urine or", "urine or bile.", "or bile. functional", "bile. functional groups", "functional groups acted", "groups acted on", "acted on include", "on include hydroxyl", "hydroxyl carboxylate", "carboxylate amino", "amino and sulfate", "and sulfate groups.", "sulfate groups. there", "groups. there are", "there are 2", "are 2 families", "2 families of", "families of ugts", "ugts ugt1", "ugt1 and ugt2", "and ugt2 which", "ugt2 which are", "which are further", "are further sub", "further sub divided", "sub divided into", "divided into 3", "into 3 subfamilies", "subfamilies ugt1a", "ugt1a ugt2a", "ugt2a and ugt2b.", "and ugt2b. there", "ugt2b. there are", "there are more", "are more than", "more than 26", "than 26 different", "26 different isozymes", "different isozymes in", "isozymes in humans", "humans of", "of which 18", "which 18 are", "18 are functional", "are functional proteins.", "functional proteins. they", "proteins. they are", "they are composed", "are composed of", "composed of 527", "of 527 530", "527 530 residues", "530 residues and", "residues and have", "and have a", "have a molecular", "a molecular weight", "molecular weight of", "weight of 50", "of 50 57kda.
the", "50 57kda.
the ugt1", "57kda.
the ugt1 family", "ugt1 family comprises", "family comprises of", "comprises of 9", "of 9 proteins", "proteins ugt1a1", "ugt1a1 1a3", "1a10 but", "but only 5", "only 5 have", "5 have been", "have been isolated", "been isolated in", "isolated in humans.", "in humans. example", "humans. example substrates", "example substrates which", "substrates which are", "which are glucuronidated", "are glucuronidated are", "glucuronidated are acetaminophen", "are acetaminophen by", "acetaminophen by ugt1a6", "by ugt1a6 and", "ugt1a6 and bilirubin", "and bilirubin by", "bilirubin by ugt1a1.", "by ugt1a1. members", "ugt1a1. members of", "members of the", "of the ugt2", "the ugt2 subfamily", "ugt2 subfamily are", "subfamily are each", "are each encoded", "each encoded by", "encoded by their", "by their own", "their own genes", "genes in", "in contrast to", "contrast to ugt1as", "to ugt1as which", "ugt1as which are", "which are encoded", "are encoded at", "encoded at the", "at the ugt1", "the ugt1 locus.", "ugt1 locus. example", "locus. example substrates", "example substrates are", "substrates are morphine", "are morphine conjugation", "morphine conjugation by", "conjugation by ugt2b7", "by ugt2b7 and", "ugt2b7 and androgenic", "and androgenic steroid", "androgenic steroid conjugation", "steroid conjugation by", "conjugation by ugt2b17.
xenobiotics", "by ugt2b17.
xenobiotics conjugated", "ugt2b17.
xenobiotics conjugated with", "conjugated with glucuronic", "with glucuronic acid", "glucuronic acid can", "acid can be", "can be substrates", "be substrates for", "substrates for beta", "for beta glucuronidase", "glucuronidase an", "an enzyme common", "enzyme common in", "common in gut", "in gut microflora.", "gut microflora. this", "microflora. this enzyme", "this enzyme can", "enzyme can release", "can release the", "release the parent", "the parent or", "parent or phase", "or phase i", "phase i metabolite", "i metabolite which", "metabolite which can", "which can be", "can be reabsorbed.", "be reabsorbed. it", "reabsorbed. it can", "it can then", "can then either", "then either re", "either re exert", "re exert it's", "exert it's original", "it's original effects", "original effects or", "effects or be", "or be conjugated", "be conjugated by", "conjugated by glucuronic", "by glucuronic acid", "glucuronic acid again.", "acid again. this", "again. this cycle", "this cycle is", "cycle is called", "is called enterohepatic", "called enterohepatic circulation", "enterohepatic circulation and", "circulation and can", "and can delay", "can delay the", "delay the elimination", "the elimination of", "elimination of the", "of the xenobiotic.", "glucuronidation conjugation utilizes udp", "conjugation utilizes udp glucuronosyltransferases", "udp glucuronosyltransferases ugts", "ugts ec 2.4.1.17", "ec 2.4.1.17 to", "2.4.1.17 to catalyze", "to catalyze a wide", "catalyze a wide range", "a wide range of", "wide range of diverse", "range of diverse endogenous", "of diverse endogenous and", "diverse endogenous and xenobiotic", "endogenous and xenobiotic compounds.", "and xenobiotic compounds. glucuronidation", "xenobiotic compounds. glucuronidation is", "compounds. glucuronidation is the", "glucuronidation is the major", "is the major pathway", "the major pathway in", "major pathway in phase", "pathway in phase ii", "in phase ii metabolism", "phase ii metabolism and", "ii metabolism and accounts", "metabolism and accounts for", "and accounts for approximately", "accounts for approximately 35%", "for approximately 35% of", "approximately 35% of drug", "35% of drug conjugation.", "of drug conjugation. ugts", "drug conjugation. ugts are", "conjugation. ugts are microsomal", "ugts are microsomal membrane", "are microsomal membrane bound", "microsomal membrane bound and", "membrane bound and catalyze", "bound and catalyze the", "and catalyze the transfer", "catalyze the transfer of", "the transfer of a", "transfer of a glucuronate", "of a glucuronate group", "a glucuronate group of", "glucuronate group of uridine", "group of uridine diphosphoglucuronate", "uridine diphosphoglucuronate udpga", "udpga a co", "co substrate to", "substrate to the", "to the functional group", "the functional group of", "functional group of specific", "group of specific substrates.", "of specific substrates. udpga", "specific substrates. udpga is", "substrates. udpga is synthesized", "udpga is synthesized from", "is synthesized from glucose", "synthesized from glucose 1", "from glucose 1 phosphate", "1 phosphate g1p", "phosphate g1p .", "g1p . g1p is", ". g1p is required", "g1p is required for", "is required for glycolysis", "required for glycolysis and", "for glycolysis and is", "glycolysis and is present", "and is present in", "is present in high", "present in high concentrations", "in high concentrations in", "high concentrations in the", "concentrations in the cell", "the cell making", "cell making it", "making it is unlikely", "it is unlikely to", "is unlikely to be", "unlikely to be a", "to be a limiting", "be a limiting factor", "a limiting factor in", "limiting factor in udpga", "factor in udpga synthesis.", "in udpga synthesis. udp", "udpga synthesis. udp is", "synthesis. udp is added", "udp is added to", "is added to g1p", "added to g1p to", "to g1p to form", "g1p to form udp", "to form udp glucose", "form udp glucose which", "udp glucose which is", "glucose which is then", "which is then dehydrogenated", "is then dehydrogenated to", "then dehydrogenated to form", "dehydrogenated to form udpga.", "to form udpga. the", "form udpga. the basic", "udpga. the basic reaction", "the basic reaction is

udp", "basic reaction is

udp glucuronate", "reaction is

udp glucuronate +", "is

udp glucuronate + acceptor", "+ acceptor >", "acceptor > udp", "> udp + acceptor", "udp + acceptor beta", "+ acceptor beta d", "acceptor beta d glucuronide

the", "beta d glucuronide

the effect", "d glucuronide

the effect of", "glucuronide

the effect of this", "effect of this conjugation", "of this conjugation is", "this conjugation is to", "conjugation is to confer", "is to confer polarity", "to confer polarity to", "confer polarity to the", "polarity to the substrate", "to the substrate which", "the substrate which can", "substrate which can then", "which can then be", "can then be easily", "then be easily excreted", "be easily excreted in", "easily excreted in urine", "excreted in urine or", "in urine or bile.", "urine or bile. functional", "or bile. functional groups", "bile. functional groups acted", "functional groups acted on", "groups acted on include", "acted on include hydroxyl", "include hydroxyl carboxylate", "carboxylate amino and", "amino and sulfate groups.", "and sulfate groups. there", "sulfate groups. there are", "groups. there are 2", "there are 2 families", "are 2 families of", "2 families of ugts", "of ugts ugt1", "ugts ugt1 and", "ugt1 and ugt2 which", "and ugt2 which are", "ugt2 which are further", "which are further sub", "are further sub divided", "further sub divided into", "sub divided into 3", "divided into 3 subfamilies", "3 subfamilies ugt1a", "ugt1a ugt2a and", "ugt2a and ugt2b. there", "and ugt2b. there are", "ugt2b. there are more", "there are more than", "are more than 26", "more than 26 different", "than 26 different isozymes", "26 different isozymes in", "different isozymes in humans", "in humans of", "humans of which", "of which 18 are", "which 18 are functional", "18 are functional proteins.", "are functional proteins. they", "functional proteins. they are", "proteins. they are composed", "they are composed of", "are composed of 527", "composed of 527 530", "of 527 530 residues", "527 530 residues and", "530 residues and have", "residues and have a", "and have a molecular", "have a molecular weight", "a molecular weight of", "molecular weight of 50", "weight of 50 57kda.
the", "of 50 57kda.
the ugt1", "50 57kda.
the ugt1 family", "57kda.
the ugt1 family comprises", "ugt1 family comprises of", "family comprises of 9", "comprises of 9 proteins", "9 proteins ugt1a1", "ugt1a1 1a3 1a10", "1a3 1a10 but", "1a10 but only", "but only 5 have", "only 5 have been", "5 have been isolated", "have been isolated in", "been isolated in humans.", "isolated in humans. example", "in humans. example substrates", "humans. example substrates which", "example substrates which are", "substrates which are glucuronidated", "which are glucuronidated are", "are glucuronidated are acetaminophen", "glucuronidated are acetaminophen by", "are acetaminophen by ugt1a6", "acetaminophen by ugt1a6 and", "by ugt1a6 and bilirubin", "ugt1a6 and bilirubin by", "and bilirubin by ugt1a1.", "bilirubin by ugt1a1. members", "by ugt1a1. members of", "ugt1a1. members of the", "members of the ugt2", "of the ugt2 subfamily", "the ugt2 subfamily are", "ugt2 subfamily are each", "subfamily are each encoded", "are each encoded by", "each encoded by their", "encoded by their own", "by their own genes", "own genes in", "genes in contrast", "in contrast to ugt1as", "contrast to ugt1as which", "to ugt1as which are", "ugt1as which are encoded", "which are encoded at", "are encoded at the", "encoded at the ugt1", "at the ugt1 locus.", "the ugt1 locus. example", "ugt1 locus. example substrates", "locus. example substrates are", "example substrates are morphine", "substrates are morphine conjugation", "are morphine conjugation by", "morphine conjugation by ugt2b7", "conjugation by ugt2b7 and", "by ugt2b7 and androgenic", "ugt2b7 and androgenic steroid", "and androgenic steroid conjugation", "androgenic steroid conjugation by", "steroid conjugation by ugt2b17.
xenobiotics", "conjugation by ugt2b17.
xenobiotics conjugated", "by ugt2b17.
xenobiotics conjugated with", "ugt2b17.
xenobiotics conjugated with glucuronic", "conjugated with glucuronic acid", "with glucuronic acid can", "glucuronic acid can be", "acid can be substrates", "can be substrates for", "be substrates for beta", "substrates for beta glucuronidase", "beta glucuronidase an", "glucuronidase an enzyme", "an enzyme common in", "enzyme common in gut", "common in gut microflora.", "in gut microflora. this", "gut microflora. this enzyme", "microflora. this enzyme can", "this enzyme can release", "enzyme can release the", "can release the parent", "release the parent or", "the parent or phase", "parent or phase i", "or phase i metabolite", "phase i metabolite which", "i metabolite which can", "metabolite which can be", "which can be reabsorbed.", "can be reabsorbed. it", "be reabsorbed. it can", "reabsorbed. it can then", "it can then either", "can then either re", "then either re exert", "either re exert it's", "re exert it's original", "exert it's original effects", "it's original effects or", "original effects or be", "effects or be conjugated", "or be conjugated by", "be conjugated by glucuronic", "conjugated by glucuronic acid", "by glucuronic acid again.", "glucuronic acid again. this", "acid again. this cycle", "again. this cycle is", "this cycle is called", "cycle is called enterohepatic", "is called enterohepatic circulation", "called enterohepatic circulation and", "enterohepatic circulation and can", "circulation and can delay", "and can delay the", "can delay the elimination", "delay the elimination of", "the elimination of the", "elimination of the xenobiotic.", "glucuronidation conjugation utilizes udp glucuronosyltransferases", "utilizes udp glucuronosyltransferases ugts", "glucuronosyltransferases ugts ec", "ec 2.4.1.17 to catalyze", "2.4.1.17 to catalyze a", "to catalyze a wide range", "catalyze a wide range of", "a wide range of diverse", "wide range of diverse endogenous", "range of diverse endogenous and", "of diverse endogenous and xenobiotic", "diverse endogenous and xenobiotic compounds.", "endogenous and xenobiotic compounds. glucuronidation", "and xenobiotic compounds. glucuronidation is", "xenobiotic compounds. glucuronidation is the", "compounds. glucuronidation is the major", "glucuronidation is the major pathway", "is the major pathway in", "the major pathway in phase", "major pathway in phase ii", "pathway in phase ii metabolism", "in phase ii metabolism and", "phase ii metabolism and accounts", "ii metabolism and accounts for", "metabolism and accounts for approximately", "and accounts for approximately 35%", "accounts for approximately 35% of", "for approximately 35% of drug", "approximately 35% of drug conjugation.", "35% of drug conjugation. ugts", "of drug conjugation. ugts are", "drug conjugation. ugts are microsomal", "conjugation. ugts are microsomal membrane", "ugts are microsomal membrane bound", "are microsomal membrane bound and", "microsomal membrane bound and catalyze", "membrane bound and catalyze the", "bound and catalyze the transfer", "and catalyze the transfer of", "catalyze the transfer of a", "the transfer of a glucuronate", "transfer of a glucuronate group", "of a glucuronate group of", "a glucuronate group of uridine", "glucuronate group of uridine diphosphoglucuronate", "of uridine diphosphoglucuronate udpga", "diphosphoglucuronate udpga a", "udpga a co substrate", "a co substrate to", "co substrate to the", "substrate to the functional", "to the functional group of", "the functional group of specific", "functional group of specific substrates.", "group of specific substrates. udpga", "of specific substrates. udpga is", "specific substrates. udpga is synthesized", "substrates. udpga is synthesized from", "udpga is synthesized from glucose", "is synthesized from glucose 1", "synthesized from glucose 1 phosphate", "glucose 1 phosphate g1p", "1 phosphate g1p .", "phosphate g1p . g1p", "g1p . g1p is required", ". g1p is required for", "g1p is required for glycolysis", "is required for glycolysis and", "required for glycolysis and is", "for glycolysis and is present", "glycolysis and is present in", "and is present in high", "is present in high concentrations", "present in high concentrations in", "in high concentrations in the", "high concentrations in the cell", "in the cell making", "the cell making it", "cell making it is", "making it is unlikely to", "it is unlikely to be", "is unlikely to be a", "unlikely to be a limiting", "to be a limiting factor", "be a limiting factor in", "a limiting factor in udpga", "limiting factor in udpga synthesis.", "factor in udpga synthesis. udp", "in udpga synthesis. udp is", "udpga synthesis. udp is added", "synthesis. udp is added to", "udp is added to g1p", "is added to g1p to", "added to g1p to form", "to g1p to form udp", "g1p to form udp glucose", "to form udp glucose which", "form udp glucose which is", "udp glucose which is then", "glucose which is then dehydrogenated", "which is then dehydrogenated to", "is then dehydrogenated to form", "then dehydrogenated to form udpga.", "dehydrogenated to form udpga. the", "to form udpga. the basic", "form udpga. the basic reaction", "udpga. the basic reaction is

udp", "the basic reaction is

udp glucuronate", "basic reaction is

udp glucuronate +", "reaction is

udp glucuronate + acceptor", "glucuronate + acceptor >", "+ acceptor > udp", "acceptor > udp +", "> udp + acceptor beta", "udp + acceptor beta d", "+ acceptor beta d glucuronide

the", "acceptor beta d glucuronide

the effect", "beta d glucuronide

the effect of", "d glucuronide

the effect of this", "glucuronide

the effect of this conjugation", "effect of this conjugation is", "of this conjugation is to", "this conjugation is to confer", "conjugation is to confer polarity", "is to confer polarity to", "to confer polarity to the", "confer polarity to the substrate", "polarity to the substrate which", "to the substrate which can", "the substrate which can then", "substrate which can then be", "which can then be easily", "can then be easily excreted", "then be easily excreted in", "be easily excreted in urine", "easily excreted in urine or", "excreted in urine or bile.", "in urine or bile. functional", "urine or bile. functional groups", "or bile. functional groups acted", "bile. functional groups acted on", "functional groups acted on include", "groups acted on include hydroxyl", "on include hydroxyl carboxylate", "hydroxyl carboxylate amino", "carboxylate amino and sulfate", "amino and sulfate groups. there", "and sulfate groups. there are", "sulfate groups. there are 2", "groups. there are 2 families", "there are 2 families of", "are 2 families of ugts", "families of ugts ugt1", "of ugts ugt1 and", "ugts ugt1 and ugt2", "ugt1 and ugt2 which are", "and ugt2 which are further", "ugt2 which are further sub", "which are further sub divided", "are further sub divided into", "further sub divided into 3", "sub divided into 3 subfamilies", "into 3 subfamilies ugt1a", "subfamilies ugt1a ugt2a", "ugt1a ugt2a and ugt2b.", "ugt2a and ugt2b. there are", "and ugt2b. there are more", "ugt2b. there are more than", "there are more than 26", "are more than 26 different", "more than 26 different isozymes", "than 26 different isozymes in", "26 different isozymes in humans", "isozymes in humans of", "in humans of which", "humans of which 18", "of which 18 are functional", "which 18 are functional proteins.", "18 are functional proteins. they", "are functional proteins. they are", "functional proteins. they are composed", "proteins. they are composed of", "they are composed of 527", "are composed of 527 530", "composed of 527 530 residues", "of 527 530 residues and", "527 530 residues and have", "530 residues and have a", "residues and have a molecular", "and have a molecular weight", "have a molecular weight of", "a molecular weight of 50", "molecular weight of 50 57kda.
the", "weight of 50 57kda.
the ugt1", "of 50 57kda.
the ugt1 family", "50 57kda.
the ugt1 family comprises", "57kda.
the ugt1 family comprises of", "ugt1 family comprises of 9", "family comprises of 9 proteins", "of 9 proteins ugt1a1", "proteins ugt1a1 1a3", "1a3 1a10 but only", "1a10 but only 5", "but only 5 have been", "only 5 have been isolated", "5 have been isolated in", "have been isolated in humans.", "been isolated in humans. example", "isolated in humans. example substrates", "in humans. example substrates which", "humans. example substrates which are", "example substrates which are glucuronidated", "substrates which are glucuronidated are", "which are glucuronidated are acetaminophen", "are glucuronidated are acetaminophen by", "glucuronidated are acetaminophen by ugt1a6", "are acetaminophen by ugt1a6 and", "acetaminophen by ugt1a6 and bilirubin", "by ugt1a6 and bilirubin by", "ugt1a6 and bilirubin by ugt1a1.", "and bilirubin by ugt1a1. members", "bilirubin by ugt1a1. members of", "by ugt1a1. members of the", "ugt1a1. members of the ugt2", "members of the ugt2 subfamily", "of the ugt2 subfamily are", "the ugt2 subfamily are each", "ugt2 subfamily are each encoded", "subfamily are each encoded by", "are each encoded by their", "each encoded by their own", "encoded by their own genes", "their own genes in", "own genes in contrast", "genes in contrast to", "in contrast to ugt1as which", "contrast to ugt1as which are", "to ugt1as which are encoded", "ugt1as which are encoded at", "which are encoded at the", "are encoded at the ugt1", "encoded at the ugt1 locus.", "at the ugt1 locus. example", "the ugt1 locus. example substrates", "ugt1 locus. example substrates are", "locus. example substrates are morphine", "example substrates are morphine conjugation", "substrates are morphine conjugation by", "are morphine conjugation by ugt2b7", "morphine conjugation by ugt2b7 and", "conjugation by ugt2b7 and androgenic", "by ugt2b7 and androgenic steroid", "ugt2b7 and androgenic steroid conjugation", "and androgenic steroid conjugation by", "androgenic steroid conjugation by ugt2b17.
xenobiotics", "steroid conjugation by ugt2b17.
xenobiotics conjugated", "conjugation by ugt2b17.
xenobiotics conjugated with", "by ugt2b17.
xenobiotics conjugated with glucuronic", "ugt2b17.
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plk1", "b1.

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plk1", "cdc2 cyclin b1.

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plk1 phosphorylates and", "b1.

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plk1", "of cdc2 cyclin b1.

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sadasivam et", "2008 sadasivam et al.", "et al. 2012 chen", "al. 2012 chen et", "2012 chen et al.", "chen et al. 2013 ." ] }, { "record_id": "GLY_000594_1_778", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1592389", "r hsa", "hsa 1592389", "r hsa 1592389" ] }, { "record_id": "GLY_000594_1_778", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of matrix", "matrix metalloproteinases", "activation of matrix", "of matrix metalloproteinases", "activation of matrix metalloproteinases", "the matrix", "previously known", "known as", "as matrixins", "are classically", "classically known", "known to", "to be", "be involved", "involved in", "in the", "the turnover", "turnover of", "of extracellular", "extracellular matrix", "components. however", "recent high", "high throughput", "throughput proteomics", "proteomics analyses", "analyses have", "have revealed", "revealed that", "that 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linear", "

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the", "1983 .

the viral", ".

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linear", ".

linear viral", "

linear viral dna", "dna is found", "is found in", "found in a", "in a complex", "a complex with", "complex with proteins", "with proteins in", "proteins in the", "in the cytoplasm", "the cytoplasm of", "cytoplasm of infected", "of infected cells.", "infected cells. these", "cells. these complexes", "complexes termed", "termed \\preintegration complexes\\", "complexes\\ pics", "pics can", "can be isolated", "be isolated and", "isolated and have", "and have been", "have been shown", "been shown to", "shown to mediate", "to mediate integration", "mediate integration of", "integration of viral", "of viral dna", "viral dna into", "dna into target", "into target dna", "target dna in", "dna in vitro", "vitro bowerman", "bowerman et al.", "et al. 1989", "1989 brown", "1987 ellison", "ellison et al.", "1990 farnet", "farnet and haseltine", "and haseltine 1990", "1990 1991", "1991 .

the", ".

the development", "

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"integrase protein colicelli", "protein colicelli and", "colicelli and goff 1985", "goff 1985 1988", "1988 panganiban and", "panganiban and temin 1983", "and temin 1983 .

the", "temin 1983 .

the viral", "1983 .

the viral genomic", ".

the viral genomic rna", "viral genomic rna is", "genomic rna is reverse", "rna is reverse transcribed", "is reverse transcribed to", "reverse transcribed to form", "transcribed to form a", "to form a linear", "form a linear double", "a linear double stranded", "linear double stranded dna", "double stranded dna molecule", "dna molecule the", "molecule the precursor", "the precursor to the", "precursor to the integrated", "to the integrated provirus", "integrated provirus brown", "provirus brown et", "brown et al. 1987", "al. 1987 1989", "1989 fujiwara and", "fujiwara and mizuuchi 1988", "and mizuuchi 1988 .", "mizuuchi 1988 . the", "1988 . the provirus", ". the provirus is", "the provirus is colinear", "provirus is colinear with", "is colinear with unintegrated", "colinear with unintegrated linear", "with unintegrated linear viral", "unintegrated linear viral dna", "viral dna dhar", "dna dhar et", "dhar et al. 1980", "al. 1980 hughes", "1980 hughes et", "hughes et al. 1978", "al. 1978 but", "1978 but differs", "but differs from the", "differs from the reverse", "from the reverse transcription", "the reverse transcription product", "reverse transcription product in", "transcription product in that", "product in that it", "in that it is", "that it is missing", "it is missing two", "is missing two bases", "missing two bases from", "two bases from each", "bases from each end", "each end hughes", "end hughes et", "hughes et al. 1981", "et al. 1981 .", "al. 1981 . flanking", "1981 . flanking the", ". flanking the integrated", "flanking the integrated hiv", "the integrated hiv provirus", "integrated hiv provirus are", "hiv provirus are direct", "provirus are direct repeats", "are direct repeats of", "direct repeats of the", "repeats of the cellular", "of the cellular dna", "the cellular dna that", "cellular dna that are", "dna that are 5", "that are 5 base", "are 5 base pairs", "5 base pairs in", "base pairs in length", "in length vincent", "length vincent et", "vincent et al. 1990", "et al. 1990 .", "al. 1990 . this", "1990 . this duplication", ". this duplication of", "this duplication of cellular", "duplication of cellular sequences", "of cellular sequences flanking", "cellular sequences flanking the", "sequences flanking the viral", "flanking the viral dna", "the viral dna is", "viral dna is generated", "dna is generated as", "is generated as a", "generated as a consequence", "as a consequence of", "a consequence of the", "consequence of the integration", "of the integration mechanism", "integration mechanism coffin", "mechanism coffin et", "al. 1997 .", "1997 .

linear viral", ".

linear viral dna", "

linear viral dna is", "viral dna is found", "dna is found in", "is found in a", "found in a complex", "in a complex with", "a complex with proteins", "complex with proteins in", "with proteins in the", "proteins in the cytoplasm", "in the cytoplasm of", "the cytoplasm of infected", "cytoplasm of infected cells.", "of infected cells. these", "infected cells. these complexes", "these complexes termed", "complexes termed \\preintegration", "\\preintegration complexes\\ pics", "pics can be", "can be isolated and", "be isolated and have", "isolated and have been", "and have been shown", "have been shown to", "been shown to mediate", "shown to mediate integration", "to mediate integration of", "mediate integration of viral", "integration of viral dna", "of viral dna into", "viral dna into target", "dna into target dna", "into target dna in", "target dna in vitro", "in vitro bowerman", "vitro bowerman et", "bowerman et al. 1989", "al. 1989 brown", "1989 brown et", "al. 1987 ellison", "1987 ellison et", "ellison et al. 1990", "al. 1990 farnet", "1990 farnet and", "farnet and haseltine 1990", "haseltine 1990 1991", "1990 1991 .", "1991 .

the development", ".

the development of", "

the development of in", "development of in vitro", "of in vitro assays", "in vitro assays with", "vitro assays with purified", "assays with purified integrase", "with purified integrase has", "purified integrase has allowed", "integrase has allowed its", "has allowed its enzymatic", "allowed its enzymatic functions", "its enzymatic functions to", "enzymatic functions to be", "functions to be elucidated.", "to be elucidated. the", "be elucidated. the provirus", "elucidated. the provirus is", "the provirus is formed", "provirus is formed by", "is formed by two", "formed by two reactions", "by two reactions catalyzed", "two reactions catalyzed by", "reactions catalyzed by the", "catalyzed by the viral", "by the viral integrase:", "the viral integrase: terminal", "viral integrase: terminal cleavage", "integrase: terminal cleavage and", "terminal cleavage and strand", "cleavage and strand transfer.", "and strand transfer. studies", "strand transfer. studies with", "transfer. studies with purified", "studies with purified integrase", "with purified integrase have", "purified integrase have shown", "integrase have shown that", "have shown that it", "shown that it is", "that it is sufficient", "it is sufficient for", "is sufficient for both", "sufficient for both 3'", "for both 3' end", "both 3' end cleavage", "end cleavage bushman", "cleavage bushman and", "bushman and craigie 1991", "craigie 1991 craigie", "1991 craigie et", "craigie et al. 1990", "al. 1990 katzman", "1990 katzman et", "katzman et al. 1989", "al. 1989 sherman", "1989 sherman and", "sherman and fyfe 1990", "fyfe 1990 and", "1990 and joining", "and joining of the", "joining of the viral", "of the viral dna", "the viral dna to", "viral dna to the", "dna to the cellular", "to the cellular chromosome", "the cellular chromosome or", "cellular chromosome or naked", "chromosome or naked target", "or naked target dna", "target dna bushman", "dna bushman et", "bushman et al. 1990", "al. 1990 craigie", "1990 craigie et", "al. 1990 katz", "1990 katz et", "katz et al. 1990", "al. 1990 . hiv", "1990 . hiv integrase", ". hiv integrase catalyze", "hiv integrase catalyze the", "integrase catalyze the removal", "catalyze the removal of", "the removal of two", "removal of two bases", "of two bases from", "two bases from the", "bases from the 3'", "from the 3' end", "the 3' end of", "3' end of each", "end of each viral", "of each viral dna", "each viral dna strand", "dna strand leaving", "strand leaving recessed", "leaving recessed 3' hydroxyl", "recessed 3' hydroxyl groups", "hydroxyl groups brown", "groups brown et", "brown et al. 1989", "al. 1989 fujiwara", "mizuuchi 1988 roth", "1988 roth et", "roth et al. 1989", "and fyfe 1990 .", "fyfe 1990 . this", "1990 . this terminal", ". this terminal cleavage", "this terminal cleavage reaction", "terminal cleavage reaction is", "cleavage reaction is required", "reaction is required for", "is required for proper", "required for proper integration.", "for proper integration. it", "proper integration. it may", "integration. it may allow", "it may allow the", "may allow the virus", "allow the virus to", "the virus to create", "virus to create a", "to create a standard", "create a standard end", "a standard end from", "standard end from viral", "end from viral dna", "from viral dna termini", "viral dna termini that", "dna termini that can", "termini that can be", "that can be heterogeneous", "can be heterogeneous due", "be heterogeneous due to", "heterogeneous due to the", "due to the terminal", "to the terminal transferase", "the terminal transferase activity", "terminal transferase activity of", "transferase activity of reverse", "activity of reverse transcriptase", "reverse transcriptase miller", "transcriptase miller et", "miller et al. 1997", "al. 1997 patel", "1997 patel and", "patel and preston 1994", "and preston 1994 .", "preston 1994 . in", "1994 . in addition", "in addition the", "addition the terminal", "the terminal cleavage step", "terminal cleavage step is", "cleavage step is coupled", "step is coupled to", "is coupled to the", "coupled to the formation", "to the formation of", "the formation of a", "formation of a stable", "of a stable integrase", "a stable integrase dna", "stable integrase dna complex", "dna complex ellison", "complex ellison and", "ellison and brown 1994", "brown 1994 vink", "1994 vink et", "vink et al. 1994", "et al. 1994 .", "al. 1994 . following", "1994 . following terminal", ". following terminal cleavage", "terminal cleavage a", "cleavage a recessed", "a recessed hydroxyl is", "recessed hydroxyl is exposed", "hydroxyl is exposed that", "is exposed that immediately", "exposed that immediately follows", "that immediately follows a", "immediately follows a ca", "follows a ca dinucleotide.", "a ca dinucleotide. more", "ca dinucleotide. more internal", "dinucleotide. more internal ltr", "more internal ltr sites", "internal ltr sites are", "ltr sites are also", "sites are also important", "are also important for", "also important for integration", "for integration balakrishnan", "integration balakrishnan and", "balakrishnan and jonsson 1997", "jonsson 1997 bushman", "1997 bushman and", "bushman and craigie 1990", "craigie 1990 leavitt", "1990 leavitt et", "leavitt et al. 1992", "et al. 1992 .", "al. 1992 . after", "1992 . after end", ". after end processing", "end processing integrase", "processing integrase catalyzes", "integrase catalyzes the covalent", "catalyzes the covalent attachment", "the covalent attachment of", "covalent attachment of hydroxyl", "attachment of hydroxyl groups", "of hydroxyl groups at", "hydroxyl groups at the", "groups at the viral", "at the viral dna", "the viral dna termini", "viral dna termini to", "dna termini to protruding", "termini to protruding 5'", "to protruding 5' phosphoryl", "protruding 5' phosphoryl ends", "5' phosphoryl ends of", "phosphoryl ends of the", "ends of the host", "of the host cell", "the host cell dna", "cell dna brown", "dna brown et", "al. 1987 brown", "1987 brown et", "1988 . the dna", ". the dna cleavage", "the dna cleavage and", "dna cleavage and joining", "cleavage and joining reactions", "and joining reactions involved", "joining reactions involved in", "reactions involved in integration", "involved in integration are", "in integration are shown", "integration are shown in", "are shown in the", "shown in the figure", "in the figure below.", "the figure below. both", "figure below. both the", "below. both the viral", "both the viral dna", "the viral dna 3'", "viral dna 3' end", "dna 3' end cleavage", "3' end cleavage and", "end cleavage and strand", "cleavage and strand transfer", "and strand transfer reactions", "strand transfer reactions are", "transfer reactions are mediated", "reactions are mediated by", "are mediated by single", "mediated by single step", "by single step transesterification", "single step transesterification chemistry", "step transesterification chemistry as", "transesterification chemistry as shown", "chemistry as shown by", "as shown by stereochemical", "shown by stereochemical analysis", "by stereochemical analysis of", "stereochemical analysis of reaction", "analysis of reaction products", "reaction products engelman", "products engelman et", "engelman et al. 1991", "et al. 1991 .", "al. 1991 . biochemical", "1991 . biochemical analysis", ". biochemical analysis of", "biochemical analysis of purified", "analysis of purified integrase", "of purified integrase revealed", "purified integrase revealed that", "integrase revealed that it", "revealed that it requires", "that it requires a", "it requires a divalent", "requires a divalent metal", "metal either", "either mg2+ or mn2+", "mn2+ to", "to carry out reactions", "carry out reactions with", "out reactions with model", "reactions with model substrates", "model substrates that", "substrates that probably", "that probably mediate the", "probably mediate the reaction", "mediate the reaction chemistry", "reaction chemistry bushman", "chemistry bushman and", "fyfe 1990 gao", "1990 gao et", "gao et al. 2004", "et al. 2004 .", "for retroviral dna to direct", "retroviral dna to direct production", "dna to direct production of", "to direct production of progeny", "direct production of progeny virions", "production of progeny virions it", "of progeny virions it must", "progeny virions it must become", "virions it must become covalently", "it must become covalently integrated", "must become covalently integrated into", "become covalently integrated into the", "covalently integrated into the host", "integrated into the host cell", "into the host cell chromosome", "host cell chromosome reviewed", "cell chromosome reviewed in", "chromosome reviewed in coffin", "reviewed in coffin et al.", "in coffin et al. 1997", "et al. 1997 hansen", "al. 1997 hansen et", "1997 hansen et al.", "hansen et al. 1998 .", "et al. 1998 . analyses", "al. 1998 . analyses of", "1998 . analyses of mutants", ". analyses of mutants have", "analyses of mutants have identified", "of mutants have identified the", "mutants have identified the viral", "have identified the viral integrase", "identified the viral integrase coding", "the viral integrase coding region", "integrase coding region part", "coding region part of", "region part of the", "part of the retroviral pol", "of the retroviral pol gene", "retroviral pol gene as", "pol gene as essential", "gene as essential for", "as essential for the integration", "essential for the integration process", "the integration process donehower", "integration process donehower 1988", "donehower 1988 donehower and", "1988 donehower and varmus", "and varmus 1984 panganiban", "varmus 1984 panganiban and", "1984 panganiban and temin", "and temin 1984 quinn", "temin 1984 quinn and", "1984 quinn and grandgenett", "and grandgenett 1988 schwartzberg", "grandgenett 1988 schwartzberg et", "1988 schwartzberg et al.", "schwartzberg et al. 1984 .", "et al. 1984 . also", "al. 1984 . also essential", "1984 . also essential are", ". also essential are regions", "also essential are regions at", "essential are regions at the", "are regions at the ends", "regions at the ends of", "at the ends of the", "the ends of the viral", "ends of the viral long", "of the viral long terminal", "the viral long terminal repeats", "long terminal repeats ltrs", "repeats ltrs that", "ltrs that serve as", "that serve as recognition sites", "serve as recognition sites for", "as recognition sites for integrase", "recognition sites for integrase protein", "for integrase protein colicelli", "integrase protein colicelli and", "protein colicelli and goff", "and goff 1985 1988", "1985 1988 panganiban", "1988 panganiban and temin", "panganiban and temin 1983 .

the", "and temin 1983 .

the viral", "temin 1983 .

the viral genomic", "1983 .

the viral genomic rna", ".

the viral genomic rna is", "viral genomic rna is reverse", "genomic rna is reverse transcribed", "rna is reverse transcribed to", "is reverse transcribed to form", "reverse transcribed to form a", "transcribed to form a linear", "to form a linear double", "form a linear double stranded", "a linear double stranded dna", "linear double stranded dna molecule", "stranded dna molecule the", "dna molecule the precursor", "molecule the precursor to", "the precursor to the integrated", "precursor to the integrated provirus", "the integrated provirus brown", "integrated provirus brown et", "provirus brown et al.", "et al. 1987 1989", "1987 1989 fujiwara", "1989 fujiwara and mizuuchi", "fujiwara and mizuuchi 1988 .", "and mizuuchi 1988 . the", "mizuuchi 1988 . the provirus", "1988 . the provirus is", ". the provirus is colinear", "the provirus is colinear with", "provirus is colinear with unintegrated", "is colinear with unintegrated linear", "colinear with unintegrated linear viral", "with unintegrated linear viral dna", "linear viral dna dhar", "viral dna dhar et", "dna dhar et al.", "et al. 1980 hughes", "al. 1980 hughes et", "1980 hughes et al.", "et al. 1978 but", "al. 1978 but differs", "1978 but differs from", "but differs from the reverse", "differs from the reverse transcription", "from the reverse transcription product", "the reverse transcription product in", "reverse transcription product in that", "transcription product in that it", "product in that it is", "in that it is missing", "that it is missing two", "it is missing two bases", "is missing two bases from", "missing two bases from each", "two bases from each end", "from each end hughes", "each end hughes et", "end hughes et al.", "hughes et al. 1981 .", "et al. 1981 . flanking", "al. 1981 . flanking the", "1981 . flanking the integrated", ". flanking the integrated hiv", "flanking the integrated hiv provirus", "the integrated hiv provirus are", "integrated hiv provirus are direct", "hiv provirus are direct repeats", "provirus are direct repeats of", "are direct repeats of the", "direct repeats of the cellular", "repeats of the cellular dna", "of the cellular dna that", "the cellular dna that are", "cellular dna that are 5", "dna that are 5 base", "that are 5 base pairs", "are 5 base pairs in", "5 base pairs in length", "pairs in length vincent", "in length vincent et", "length vincent et al.", "vincent et al. 1990 .", "et al. 1990 . this", "al. 1990 . this duplication", "1990 . this duplication of", ". this duplication of cellular", "this duplication of cellular sequences", "duplication of cellular sequences flanking", "of cellular sequences flanking the", "cellular sequences flanking the viral", "sequences flanking the viral dna", "flanking the viral dna is", "the viral dna is generated", "viral dna is generated as", "dna is generated as a", "is generated as a consequence", "generated as a consequence of", "as a consequence of the", "a consequence of the integration", "consequence of the integration mechanism", "the integration mechanism coffin", "integration mechanism coffin et", "mechanism coffin et al.", "et al. 1997 .", "al. 1997 .

linear", "1997 .

linear viral dna", ".

linear viral dna is", "

linear viral dna is found", "viral dna is found in", "dna is found in a", "is found in a complex", "found in a complex with", "in a complex with proteins", "a complex with proteins in", "complex with proteins in the", "with proteins in the cytoplasm", "proteins in the cytoplasm of", "in the cytoplasm of infected", "the cytoplasm of infected cells.", "cytoplasm of infected cells. these", "of infected cells. these complexes", "cells. these complexes termed", "these complexes termed \\preintegration", "complexes termed \\preintegration complexes\\", "termed \\preintegration complexes\\ pics", "complexes\\ pics can", "pics can be isolated", "can be isolated and have", "be isolated and have been", "isolated and have been shown", "and have been shown to", "have been shown to mediate", "been shown to mediate integration", "shown to mediate integration of", "to mediate integration of viral", "mediate integration of viral dna", "integration of viral dna into", "of viral dna into target", "viral dna into target dna", "dna into target dna in", "into target dna in vitro", "dna in vitro bowerman", "in vitro bowerman et", "vitro bowerman et al.", "et al. 1989 brown", "al. 1989 brown et", "1989 brown et al.", "et al. 1987 ellison", "al. 1987 ellison et", "1987 ellison et al.", "et al. 1990 farnet", "al. 1990 farnet and", "1990 farnet and haseltine", "and haseltine 1990 1991", "haseltine 1990 1991 .", "1990 1991 .

the", "1991 .

the development of", ".

the development of in", "

the development of in vitro", "development of in vitro assays", "of in vitro assays with", "in vitro assays with purified", "vitro assays with purified integrase", "assays with purified integrase has", "with purified integrase has allowed", "purified integrase has allowed its", "integrase has allowed its enzymatic", "has allowed its enzymatic functions", "allowed its enzymatic functions to", "its enzymatic functions to be", "enzymatic functions to be elucidated.", "functions to be elucidated. the", "to be elucidated. the provirus", "be elucidated. the provirus is", "elucidated. the provirus is formed", "the provirus is formed by", "provirus is formed by two", "is formed by two reactions", "formed by two reactions catalyzed", "by two reactions catalyzed by", "two reactions catalyzed by the", "reactions catalyzed by the viral", "catalyzed by the viral integrase:", "by the viral integrase: terminal", "the viral integrase: terminal cleavage", "viral integrase: terminal cleavage and", "integrase: terminal cleavage and strand", "terminal cleavage and strand transfer.", "cleavage and strand transfer. studies", "and strand transfer. studies with", "strand transfer. studies with purified", "transfer. studies with purified integrase", "studies with purified integrase have", "with purified integrase have shown", "purified integrase have shown that", "integrase have shown that it", "have shown that it is", "shown that it is sufficient", "that it is sufficient for", "it is sufficient for both", "is sufficient for both 3'", "sufficient for both 3' end", "for both 3' end cleavage", "3' end cleavage bushman", "end cleavage bushman and", "cleavage bushman and craigie", "and craigie 1991 craigie", "craigie 1991 craigie et", "1991 craigie et al.", "et al. 1990 katzman", "al. 1990 katzman et", "1990 katzman et al.", "et al. 1989 sherman", "al. 1989 sherman and", "1989 sherman and fyfe", "and fyfe 1990 and", "fyfe 1990 and joining", "1990 and joining of", "and joining of the viral", "joining of the viral dna", "of the viral dna to", "the viral dna to the", "viral dna to the cellular", "dna to the cellular chromosome", "to the cellular chromosome or", "the cellular chromosome or naked", "cellular chromosome or naked target", "chromosome or naked target dna", "naked target dna bushman", "target dna bushman et", "dna bushman et al.", "et al. 1990 craigie", "al. 1990 craigie et", "1990 craigie et al.", "et al. 1990 katz", "al. 1990 katz et", "1990 katz et al.", "katz et al. 1990 .", "et al. 1990 . hiv", "al. 1990 . hiv integrase", "1990 . hiv integrase catalyze", ". hiv integrase catalyze the", "hiv integrase catalyze the removal", "integrase catalyze the removal of", "catalyze the removal of two", "the removal of two bases", "removal of two bases from", "of two bases from the", "two bases from the 3'", "bases from the 3' end", "from the 3' end of", "the 3' end of each", "3' end of each viral", "end of each viral dna", "of each viral dna strand", "viral dna strand leaving", "dna strand leaving recessed", "strand leaving recessed 3'", "leaving recessed 3' hydroxyl groups", "3' hydroxyl groups brown", "hydroxyl groups brown et", "groups brown et al.", "et al. 1989 fujiwara", "al. 1989 fujiwara and", "and mizuuchi 1988 roth", "mizuuchi 1988 roth et", "1988 roth et al.", "sherman and fyfe 1990 .", "and fyfe 1990 . this", "fyfe 1990 . this terminal", "1990 . this terminal cleavage", ". this terminal cleavage reaction", "this terminal cleavage reaction is", "terminal cleavage reaction is required", "cleavage reaction is required for", "reaction is required for proper", "is required for proper integration.", "required for proper integration. it", "for proper integration. it may", "proper integration. it may allow", "integration. it may allow the", "it may allow the virus", "may allow the virus to", "allow the virus to create", "the virus to create a", "virus to create a standard", "to create a standard end", "create a standard end from", "a standard end from viral", "standard end from viral dna", "end from viral dna termini", "from viral dna termini that", "viral dna termini that can", "dna termini that can be", "termini that can be heterogeneous", "that can be heterogeneous due", "can be heterogeneous due to", "be heterogeneous due to the", "heterogeneous due to the terminal", "due to the terminal transferase", "to the terminal transferase activity", "the terminal transferase activity of", "terminal transferase activity of reverse", "transferase activity of reverse transcriptase", "of reverse transcriptase miller", "reverse transcriptase miller et", "transcriptase miller et al.", "et al. 1997 patel", "al. 1997 patel and", "1997 patel and preston", "patel and preston 1994 .", "and preston 1994 . in", "preston 1994 . in addition", ". in addition the", "in addition the terminal", "addition the terminal cleavage", "the terminal cleavage step is", "terminal cleavage step is coupled", "cleavage step is coupled to", "step is coupled to the", "is coupled to the formation", "coupled to the formation of", "to the formation of a", "the formation of a stable", "formation of a stable integrase", "of a stable integrase dna", "a stable integrase dna complex", "integrase dna complex ellison", "dna complex ellison and", "complex ellison and brown", "and brown 1994 vink", "brown 1994 vink et", "1994 vink et al.", "vink et al. 1994 .", "et al. 1994 . following", "al. 1994 . following terminal", "1994 . following terminal cleavage", "following terminal cleavage a", "terminal cleavage a recessed", "cleavage a recessed hydroxyl", "a recessed hydroxyl is exposed", "recessed hydroxyl is exposed that", "hydroxyl is exposed that immediately", "is exposed that immediately follows", "exposed that immediately follows a", "that immediately follows a ca", "immediately follows a ca dinucleotide.", "follows a ca dinucleotide. more", "a ca dinucleotide. more internal", "ca dinucleotide. more internal ltr", "dinucleotide. more internal ltr sites", "more internal ltr sites are", "internal ltr sites are also", "ltr sites are also important", "sites are also important for", "are also important for integration", "important for integration balakrishnan", "for integration balakrishnan and", "integration balakrishnan and jonsson", "and jonsson 1997 bushman", "jonsson 1997 bushman and", "1997 bushman and craigie", "and craigie 1990 leavitt", "craigie 1990 leavitt et", "1990 leavitt et al.", "leavitt et al. 1992 .", "et al. 1992 . after", "al. 1992 . after end", "1992 . after end processing", "after end processing integrase", "end processing integrase catalyzes", "processing integrase catalyzes the", "integrase catalyzes the covalent attachment", "catalyzes the covalent attachment of", "the covalent attachment of hydroxyl", "covalent attachment of hydroxyl groups", "attachment of hydroxyl groups at", "of hydroxyl groups at the", "hydroxyl groups at the viral", "groups at the viral dna", "at the viral dna termini", "the viral dna termini to", "viral dna termini to protruding", "dna termini to protruding 5'", "termini to protruding 5' phosphoryl", "to protruding 5' phosphoryl ends", "protruding 5' phosphoryl ends of", "5' phosphoryl ends of the", "phosphoryl ends of the host", "ends of the host cell", "of the host cell dna", "host cell dna brown", "cell dna brown et", "dna brown et al.", "et al. 1987 brown", "al. 1987 brown et", "1987 brown et al.", "mizuuchi 1988 . the dna", "1988 . the dna cleavage", ". the dna cleavage and", "the dna cleavage and joining", "dna cleavage and joining reactions", "cleavage and joining reactions involved", "and joining reactions involved in", "joining reactions involved in integration", "reactions involved in integration are", "involved in integration are shown", "in integration are shown in", "integration are shown in the", "are shown in the figure", "shown in the figure below.", "in the figure below. both", "the figure below. both the", "figure below. both the viral", "below. both the viral dna", "both the viral dna 3'", "the viral dna 3' end", "viral dna 3' end cleavage", "dna 3' end cleavage and", "3' end cleavage and strand", "end cleavage and strand transfer", "cleavage and strand transfer reactions", "and strand transfer reactions are", "strand transfer reactions are mediated", "transfer reactions are mediated by", "reactions are mediated by single", "are mediated by single step", "mediated by single step transesterification", "by single step transesterification chemistry", "single step transesterification chemistry as", "step transesterification chemistry as shown", "transesterification chemistry as shown by", "chemistry as shown by stereochemical", "as shown by stereochemical analysis", "shown by stereochemical analysis of", "by stereochemical analysis of reaction", "stereochemical analysis of reaction products", "of reaction products engelman", "reaction products engelman et", "products engelman et al.", "engelman et al. 1991 .", "et al. 1991 . biochemical", "al. 1991 . biochemical analysis", "1991 . biochemical analysis of", ". biochemical analysis of purified", "biochemical analysis of purified integrase", "analysis of purified integrase revealed", "of purified integrase revealed that", "purified integrase revealed that it", "integrase revealed that it requires", "revealed that it requires a", "that it requires a divalent", "it requires a divalent metal", "divalent metal either", "metal either mg2+", "or mn2+ to", "mn2+ to carry", "to carry out reactions with", "carry out reactions with model", "out reactions with model substrates", "with model substrates that", "model substrates that probably", "substrates that probably mediate", "that probably mediate the reaction", "probably mediate the reaction chemistry", "the reaction chemistry bushman", "reaction chemistry bushman and", "chemistry bushman and craigie", "and fyfe 1990 gao", "fyfe 1990 gao et", "1990 gao et al.", "gao et al. 2004 ." ] }, { "record_id": "GLY_000594_1_785", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162658", "r hsa", "hsa 162658", "r hsa 162658" ] }, { "record_id": "GLY_000594_1_785", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "golgi cisternae", "cisternae pericentriolar", "pericentriolar stack", "stack reorganization", "golgi cisternae pericentriolar", "cisternae pericentriolar stack", "pericentriolar stack reorganization", "golgi cisternae pericentriolar stack", "cisternae pericentriolar stack reorganization", "golgi cisternae pericentriolar stack reorganization", "the pericentriolar", "pericentriolar stacks", "stacks of", "of golgi", "cisternae undergo", "undergo extensive", "extensive fragmentation", "fragmentation and", "and reorganization", "reorganization in", "in mitosis.
", "
in mammalian", "mammalian cells", "golgi apparatus", "apparatus consists", "consists of", "of stacked", "stacked cisternae", "cisternae that", "that are", "are connected", "connected by", "by tubules", "tubules to", "to form", "form a", "a ribbon", "ribbon like", "like structure", "structure in", "in the", "the perinuclear", "perinuclear region", "in vicinity", "vicinity of", "of the", "the centrosome.", "centrosome. reorganization", "reorganization of", "the golgi", "apparatus during", "during cell", "cell division", "division allows", "allows both", "both daughter", "daughter cells", "cells to", "to inherit", "inherit this", "this organelle", "and may", "may play", "play additional", "additional roles", "roles in", "the organization", "organization of", "the mitotic", "mitotic spindle.", "spindle.
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", "

from", "
from prophase", "prophase to", "to metaphase", "fragmentation that", "that is", "is a", "a consequence", "consequence of", "of unstacking", "unstacking of", "cisternae and", "and cessation", "cessation of", "of transport", "transport through", "through golgi.", "golgi. at", "at least", "least three", "three mitotic", "mitotic kinases", "plk1 and", "and mek1", "regulate these", "these changes.", "changes. cdk1", "cdk1 in", "in complex", "complex with", "with cyclin", "cyclin b", "b phosphorylates", "phosphorylates golga2", "and gorasp1", "constituents of", "of a", "a cis", "cis golgi", "golgi membrane", "membrane complex", "lowe et", "al. 1998", "preisinger et", "al. 2005", "2005 .", ". phosphorylation", "phosphorylation of", "of golga2", "golga2 prevents", "prevents binding", "binding of", "of uso1", "a protein", "protein localizing", "localizing to", "to the", "the membrane", "membrane of", "of er", "endoplasmic reticulum", "to golgi", "golgi transport", "transport vesicles", "vesicles and", "and cis", "thereby impairing", "impairing fusion", "fusion of", "of these", "these vesicles", "vesicles with", "with cis", "and stopping", "stopping er", "er to", "seeman et", "al. 2000", "moyer et", "al. 2001", "2001 .", "of gorasp1", "gorasp1 by", "by cdk1", "cdk1 enables", "enables further", "further phosphorylation", "by plk1", "cdk1 and", "and plk1", "plk1 impairs", "impairs stacking", "stacking of", "cisternae by", "by interfering", "interfering with", "with formation", "formation of", "gorasp1 trans", "trans oligomers", "oligomers that", "that would", "would normally", "normally link", "link the", "cisternae together", "wang et", "al. 2003", "sengupta and", "linstedt 2010", "2010 .", ".

", "

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", "mitosis.

in", "
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", "spindle.

first", "

first changes", "
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", ".

from", "

from prophase", "
from prophase to", "prophase to metaphase", "metaphase golgi", "extensive fragmentation that", "fragmentation that is", "that is a", "is a consequence", "a consequence of", "consequence of unstacking", "of unstacking of", "unstacking of golgi", "golgi cisternae and", "cisternae and cessation", "and cessation of", "cessation of transport", "of transport through", "transport through golgi.", "through golgi. at", "golgi. at least", "at least three", "least three mitotic", "three mitotic kinases", "kinases cdk1", "cdk1 plk1", "plk1 and mek1", "mek1 regulate", "regulate these changes.", "these changes. cdk1", "changes. cdk1 in", "cdk1 in complex", "in complex with", "complex with cyclin", "with cyclin b", "cyclin b phosphorylates", "b phosphorylates golga2", "golga2 gm130", "gm130 and", "gorasp1 grasp65", "constituents of a", "of a cis", "a cis golgi", "cis golgi membrane", "golgi membrane complex", "complex lowe", "lowe et al.", "et al. 1998", "1998 preisinger", "preisinger et al.", "et al. 2005", "al. 2005 .", "2005 . phosphorylation", ". phosphorylation of", "phosphorylation of golga2", "of golga2 prevents", "golga2 prevents binding", "prevents binding of", "binding of uso1", "uso1 p115", "a protein localizing", "protein localizing to", "localizing to the", "to the membrane", "the membrane of", "membrane of er", "er endoplasmic", "reticulum to", "to golgi transport", "golgi transport vesicles", "transport vesicles and", "vesicles and cis", "and cis golgi", "golgi thereby", "thereby impairing fusion", "impairing fusion of", "fusion of these", "of these vesicles", "these vesicles with", "vesicles with cis", "with cis golgi", "cis golgi cisternae", "cisternae and stopping", "and stopping er", "stopping er to", "er to golgi", "transport lowe", "1998 seeman", "seeman et al.", "et al. 2000", "2000 moyer", "moyer et al.", "et al. 2001", "al. 2001 .", "2001 . phosphorylation", "phosphorylation of gorasp1", "of gorasp1 by", "gorasp1 by cdk1", "by cdk1 enables", "cdk1 enables further", "enables further phosphorylation", "further phosphorylation of", "gorasp1 by plk1", "plk1 sutterlin", "2001 preisinger", "by cdk1 and", "cdk1 and plk1", "and plk1 impairs", "plk1 impairs stacking", "impairs stacking of", "stacking of golgi", "golgi cisternae by", "cisternae by interfering", "by interfering with", "interfering with formation", "with formation of", "formation of gorasp1", "of gorasp1 trans", "gorasp1 trans oligomers", "trans oligomers that", "oligomers that would", "that would normally", "would normally link", "normally link the", "link the golgi", "the golgi cisternae", "golgi cisternae together", "together wang", "wang et al.", "et al. 2003", "2003 wang", "2005 sengupta", "sengupta and linstedt", "and linstedt 2010", "linstedt 2010 .", "2010 .

", ".

in", "

in the", "in the median", "the median golgi", "golgi gorasp2", "gorasp2 grasp55", "a protein that", "protein that forms", "that forms a", "forms a complex", "a complex with", "complex with blfz1", "blfz1 golgin", "45 and", "and rab2a gtpase", "rab2a gtpase and", "gtpase and contributes", "and contributes to", "contributes to cisternae", "to cisternae stacking", "cisternae stacking and", "stacking and golgi", "and golgi trafficking", "trafficking short", "short et al.", "is also phosphorylated", "also phosphorylated in", "phosphorylated in mitosis.", "in mitosis. phosphorylation", "mitosis. phosphorylation of", "phosphorylation of gorasp2", "of gorasp2 by", "gorasp2 by mek1/2", "by mek1/2 activated", "mek1/2 activated mapk1", "mapk1 erk2", "erk2 and/or", "and/or mapk3 3", "3 erk1b", "erk1b in human", "human erk1c", "erk1c in rat", "rat contributes", "contributes to golgi", "to golgi unlinking", "golgi unlinking in", "unlinking in g2", "g2 and fragmentation", "and fragmentation of", "fragmentation of golgi", "golgi cisternae in", "cisternae in mitotic", "in mitotic prophase", "prophase acharya", "acharya et al.", "1998 jesch", "jesch et al.", "2001 colanzi", "2003 shaul", "shaul and seger", "and seger 2006", "2006 duran", "duran et al.", "et al. 2008", "2008 feinstein", "2007 feinstein", "and linstedt 2008", "2008 xiang", "xiang and wang", "and wang 2010", "wang 2010 .", "the pericentriolar stacks of", "pericentriolar stacks of golgi", "stacks of golgi cisternae", "of golgi cisternae undergo", "golgi cisternae undergo extensive", "cisternae undergo extensive fragmentation", "undergo extensive fragmentation and", "extensive fragmentation and reorganization", "fragmentation and reorganization in", "and reorganization in mitosis.
", "in mitosis.

in", "mitosis.

in mammalian", "mammalian cells golgi", "cells golgi apparatus", "golgi apparatus consists of", "apparatus consists of stacked", "consists of stacked cisternae", "of stacked cisternae that", "stacked cisternae that are", "cisternae that are connected", "that are connected by", "are connected by tubules", "connected by tubules to", "by tubules to form", "tubules to form a", "to form a ribbon", "form a ribbon like", "a ribbon like structure", "ribbon like structure in", "like structure in the", "structure in the perinuclear", "in the perinuclear region", "perinuclear region in", "region in vicinity", "in vicinity of the", "vicinity of the centrosome.", "of the centrosome. reorganization", "the centrosome. reorganization of", "centrosome. reorganization of the", "reorganization of the golgi", "of the golgi apparatus", "the golgi apparatus during", "golgi apparatus during cell", "apparatus during cell division", "during cell division allows", "cell division allows both", "division allows both daughter", "allows both daughter cells", "both daughter cells to", "daughter cells to inherit", "cells to inherit this", "to inherit this organelle", "this organelle and", "organelle and may", "and may play additional", "may play additional roles", "play additional roles in", "additional roles in the", "roles in the organization", "in the organization of", "the organization of the", "organization of the mitotic", "of the mitotic spindle.", "the mitotic spindle.
", "mitotic spindle.

first", "spindle.

first changes", "

first changes in", "
first changes in the", "changes in the structure", "in the structure of", "the structure of the", "structure of the golgi", "the golgi apparatus likely", "golgi apparatus likely start", "apparatus likely start in", "likely start in g2", "start in g2 and", "in g2 and are", "g2 and are subtle", "are subtle involving", "subtle involving unlinking", "involving unlinking of the", "unlinking of the golgi", "of the golgi ribbon", "the golgi ribbon into", "golgi ribbon into separate", "ribbon into separate stacks.", "into separate stacks. these", "separate stacks. these changes", "stacks. these changes are", "these changes are required", "changes are required for", "are required for the", "required for the entry", "for the entry of", "the entry of mammalian", "entry of mammalian cells", "of mammalian cells into", "mammalian cells into mitosis", "into mitosis sutterlin", "mitosis sutterlin et", "sutterlin et al. 2002", "et al. 2002 .", "al. 2002 . this", "2002 . this initial", ". this initial unlinking", "this initial unlinking of", "initial unlinking of the", "the golgi ribbon depends", "golgi ribbon depends on", "ribbon depends on grasp", "depends on grasp proteins", "on grasp proteins and", "grasp proteins and on", "proteins and on ctbp1", "on ctbp1 bars", "protein which induces", "which induces the cleavage", "induces the cleavage of", "the cleavage of the", "cleavage of the tubular", "of the tubular membranes", "the tubular membranes connecting", "tubular membranes connecting the", "membranes connecting the stacks", "the stacks hidalgo", "stacks hidalgo carcedo", "hidalgo carcedo et al.", "carcedo et al. 2004", "al. 2004 colanzi", "2004 colanzi et", "colanzi et al. 2007", "2007 but", "but the exact mechanism", "the exact mechanism is", "exact mechanism is not", "mechanism is not known.", "is not known. activation", "not known. activation of", "known. activation of mek1/2", "activation of mek1/2 also", "of mek1/2 also contributes", "mek1/2 also contributes to", "also contributes to unlinking", "contributes to unlinking of", "to unlinking of the", "the golgi ribbon in", "golgi ribbon in g2", "in g2 feinstein", "g2 feinstein and", "feinstein and linstedt 2007", "and linstedt 2007 .", "linstedt 2007 .
", "2007 .

from", ".

from prophase", "

from prophase to", "
from prophase to metaphase", "to metaphase golgi", "metaphase golgi cisternae", "undergo extensive fragmentation that", "extensive fragmentation that is", "fragmentation that is a", "that is a consequence", "is a consequence of", "a consequence of unstacking", "consequence of unstacking of", "of unstacking of golgi", "unstacking of golgi cisternae", "of golgi cisternae and", "golgi cisternae and cessation", "cisternae and cessation of", "and cessation of transport", "cessation of transport through", "of transport through golgi.", "transport through golgi. at", "through golgi. at least", "golgi. at least three", "at least three mitotic", "least three mitotic kinases", "mitotic kinases cdk1", "cdk1 plk1 and", "and mek1 regulate", "mek1 regulate these", "regulate these changes. cdk1", "these changes. cdk1 in", "changes. cdk1 in complex", "cdk1 in complex with", "in complex with cyclin", "complex with cyclin b", "with cyclin b phosphorylates", "cyclin b phosphorylates golga2", "phosphorylates golga2 gm130", "gm130 and gorasp1", "and gorasp1 grasp65", "grasp65 constituents", "constituents of a cis", "of a cis golgi", "a cis golgi membrane", "cis golgi membrane complex", "membrane complex lowe", "complex lowe et", "lowe et al. 1998", "al. 1998 preisinger", "1998 preisinger et", "preisinger et al. 2005", "et al. 2005 .", "al. 2005 . phosphorylation", "2005 . phosphorylation of", ". phosphorylation of golga2", "phosphorylation of golga2 prevents", "of golga2 prevents binding", "golga2 prevents binding of", "prevents binding of uso1", "of uso1 p115", "p115 a", "a protein localizing to", "protein localizing to the", "localizing to the membrane", "to the membrane of", "the membrane of er", "of er endoplasmic", "er endoplasmic reticulum", "endoplasmic reticulum to", "reticulum to golgi", "to golgi transport vesicles", "golgi transport vesicles and", "transport vesicles and cis", "vesicles and cis golgi", "cis golgi thereby", "golgi thereby impairing", "thereby impairing fusion of", "impairing fusion of these", "fusion of these vesicles", "of these vesicles with", "these vesicles with cis", "vesicles with cis golgi", "with cis golgi cisternae", "cis golgi cisternae and", "golgi cisternae and stopping", "cisternae and stopping er", "and stopping er to", "stopping er to golgi", "er to golgi transport", "golgi transport lowe", "transport lowe et", "al. 1998 seeman", "1998 seeman et", "seeman et al. 2000", "al. 2000 moyer", "2000 moyer et", "moyer et al. 2001", "et al. 2001 .", "al. 2001 . phosphorylation", "2001 . phosphorylation of", ". phosphorylation of gorasp1", "phosphorylation of gorasp1 by", "of gorasp1 by cdk1", "gorasp1 by cdk1 enables", "by cdk1 enables further", "cdk1 enables further phosphorylation", "enables further phosphorylation of", "further phosphorylation of gorasp1", "of gorasp1 by plk1", "by plk1 sutterlin", "plk1 sutterlin et", "sutterlin et al. 2001", "al. 2001 preisinger", "2001 preisinger et", "gorasp1 by cdk1 and", "by cdk1 and plk1", "cdk1 and plk1 impairs", "and plk1 impairs stacking", "plk1 impairs stacking of", "impairs stacking of golgi", "stacking of golgi cisternae", "of golgi cisternae by", "golgi cisternae by interfering", "cisternae by interfering with", "by interfering with formation", "interfering with formation of", "with formation of gorasp1", "formation of gorasp1 trans", "of gorasp1 trans oligomers", "gorasp1 trans oligomers that", "trans oligomers that would", "oligomers that would normally", "that would normally link", "would normally link the", "normally link the golgi", "link the golgi cisternae", "the golgi cisternae together", "cisternae together wang", "together wang et", "wang et al. 2003", "al. 2003 wang", "2003 wang et", "wang et al. 2005", "al. 2005 sengupta", "2005 sengupta and", "sengupta and linstedt 2010", "and linstedt 2010 .", "linstedt 2010 .

", "2010 .

in", ".

in the", "

in the median", "in the median golgi", "median golgi gorasp2", "grasp55 a", "a protein that forms", "protein that forms a", "that forms a complex", "forms a complex with", "a complex with blfz1", "with blfz1 golgin", "blfz1 golgin 45", "golgin 45 and", "45 and rab2a", "and rab2a gtpase and", "rab2a gtpase and contributes", "gtpase and contributes to", "and contributes to cisternae", "contributes to cisternae stacking", "to cisternae stacking and", "cisternae stacking and golgi", "stacking and golgi trafficking", "golgi trafficking short", "trafficking short et", "short et al. 2001", "2001 is", "is also phosphorylated in", "also phosphorylated in mitosis.", "phosphorylated in mitosis. phosphorylation", "in mitosis. phosphorylation of", "mitosis. phosphorylation of gorasp2", "phosphorylation of gorasp2 by", "of gorasp2 by mek1/2", "gorasp2 by mek1/2 activated", "by mek1/2 activated mapk1", "activated mapk1 erk2", "erk2 and/or mapk3", "mapk3 3 erk1b", "3 erk1b in", "in human erk1c", "human erk1c in", "in rat contributes", "rat contributes to", "contributes to golgi unlinking", "to golgi unlinking in", "golgi unlinking in g2", "unlinking in g2 and", "in g2 and fragmentation", "g2 and fragmentation of", "and fragmentation of golgi", "fragmentation of golgi cisternae", "of golgi cisternae in", "golgi cisternae in mitotic", "cisternae in mitotic prophase", "mitotic prophase acharya", "prophase acharya et", "acharya et al. 1998", "al. 1998 jesch", "1998 jesch et", "jesch et al. 2001", "al. 2001 colanzi", "2001 colanzi et", "colanzi et al. 2003", "al. 2003 shaul", "2003 shaul and", "shaul and seger 2006", "seger 2006 duran", "2006 duran et", "duran et al. 2008", "al. 2008 feinstein", "2008 feinstein and", "linstedt 2007 feinstein", "2007 feinstein and", "feinstein and linstedt 2008", "linstedt 2008 xiang", "2008 xiang and", "xiang and wang 2010", "and wang 2010 .", "the pericentriolar stacks of golgi", "pericentriolar stacks of golgi cisternae", "stacks of golgi cisternae undergo", "of golgi cisternae undergo extensive", "golgi cisternae undergo extensive fragmentation", "cisternae undergo extensive fragmentation and", "undergo extensive fragmentation and reorganization", "extensive fragmentation and reorganization in", "fragmentation and reorganization in mitosis.
", "reorganization in mitosis.

in", "in mitosis.

in mammalian", "mitosis.

in mammalian cells", "
in mammalian cells golgi", "mammalian cells golgi apparatus", "cells golgi apparatus consists", "golgi apparatus consists of stacked", "apparatus consists of stacked cisternae", "consists of stacked cisternae that", "of stacked cisternae that are", "stacked cisternae that are connected", "cisternae that are connected by", "that are connected by tubules", "are connected by tubules to", "connected by tubules to form", "by tubules to form a", "tubules to form a ribbon", "to form a ribbon like", "form a ribbon like structure", "a ribbon like structure in", "ribbon like structure in the", "like structure in the perinuclear", "structure in the perinuclear region", "the perinuclear region in", "perinuclear region in vicinity", "region in vicinity of", "in vicinity of the centrosome.", "vicinity of the centrosome. reorganization", "of the centrosome. reorganization of", "the centrosome. reorganization of the", "centrosome. reorganization of the golgi", "reorganization of the golgi apparatus", "of the golgi apparatus during", "the golgi apparatus during cell", "golgi apparatus during cell division", "apparatus during cell division allows", "during cell division allows both", "cell division allows both daughter", "division allows both daughter cells", "allows both daughter cells to", "both daughter cells to inherit", "daughter cells to inherit this", "cells to inherit this organelle", "inherit this organelle and", "this organelle and may", "organelle and may play", "and may play additional roles", "may play additional roles in", "play additional roles in the", "additional roles in the organization", "roles in the organization of", "in the organization of the", "the organization of the mitotic", "organization of the mitotic spindle.", "of the mitotic spindle.
", "the mitotic spindle.

first", "mitotic spindle.

first changes", "spindle.

first changes in", "

first changes in the", "
first changes in the structure", "changes in the structure of", "in the structure of the", "the structure of the golgi", "structure of the golgi apparatus", "of the golgi apparatus likely", "the golgi apparatus likely start", "golgi apparatus likely start in", "apparatus likely start in g2", "likely start in g2 and", "start in g2 and are", "in g2 and are subtle", "and are subtle involving", "are subtle involving unlinking", "subtle involving unlinking of", "involving unlinking of the golgi", "unlinking of the golgi ribbon", "of the golgi ribbon into", "the golgi ribbon into separate", "golgi ribbon into separate stacks.", "ribbon into separate stacks. these", "into separate stacks. these changes", "separate stacks. these changes are", "stacks. these changes are required", "these changes are required for", "changes are required for the", "are required for the entry", "required for the entry of", "for the entry of mammalian", "the entry of mammalian cells", "entry of mammalian cells into", "of mammalian cells into mitosis", "cells into mitosis sutterlin", "into mitosis sutterlin et", "mitosis sutterlin et al.", "sutterlin et al. 2002 .", "et al. 2002 . this", "al. 2002 . this initial", "2002 . this initial unlinking", ". this initial unlinking of", "this initial unlinking of the", "initial unlinking of the golgi", "of the golgi ribbon depends", "the golgi ribbon depends on", "golgi ribbon depends on grasp", "ribbon depends on grasp proteins", "depends on grasp proteins and", "on grasp proteins and on", "grasp proteins and on ctbp1", "and on ctbp1 bars", "ctbp1 bars protein", "bars protein which", "protein which induces the", "which induces the cleavage of", "induces the cleavage of the", "the cleavage of the tubular", "cleavage of the tubular membranes", "of the tubular membranes connecting", "the tubular membranes connecting the", "tubular membranes connecting the stacks", "connecting the stacks hidalgo", "the stacks hidalgo carcedo", "stacks hidalgo carcedo et", "hidalgo carcedo et al. 2004", "et al. 2004 colanzi", "al. 2004 colanzi et", "2004 colanzi et al.", "al. 2007 but", "2007 but the", "but the exact mechanism is", "the exact mechanism is not", "exact mechanism is not known.", "mechanism is not known. activation", "is not known. activation of", "not known. activation of mek1/2", "known. activation of mek1/2 also", "activation of mek1/2 also contributes", "of mek1/2 also contributes to", "mek1/2 also contributes to unlinking", "also contributes to unlinking of", "contributes to unlinking of the", "to unlinking of the golgi", "of the golgi ribbon in", "the golgi ribbon in g2", "ribbon in g2 feinstein", "in g2 feinstein and", "g2 feinstein and linstedt", "feinstein and linstedt 2007 .", "and linstedt 2007 .
", "linstedt 2007 .

from", "2007 .

from prophase", ".

from prophase to", "

from prophase to metaphase", "prophase to metaphase golgi", "to metaphase golgi cisternae", "metaphase golgi cisternae undergo", "cisternae undergo extensive fragmentation that", "undergo extensive fragmentation that is", "extensive fragmentation that is a", "fragmentation that is a consequence", "that is a consequence of", "is a consequence of unstacking", "a consequence of unstacking of", "consequence of unstacking of golgi", "of unstacking of golgi cisternae", "unstacking of golgi cisternae and", "of golgi cisternae and cessation", "golgi cisternae and cessation of", "cisternae and cessation of transport", "and cessation of transport through", "cessation of transport through golgi.", "of transport through golgi. at", "transport through golgi. at least", "through golgi. at least three", "golgi. at least three mitotic", "at least three mitotic kinases", "three mitotic kinases cdk1", "kinases cdk1 plk1", "cdk1 plk1 and mek1", "plk1 and mek1 regulate", "and mek1 regulate these", "mek1 regulate these changes.", "regulate these changes. cdk1 in", "these changes. cdk1 in complex", "changes. cdk1 in complex with", "cdk1 in complex with cyclin", "in complex with cyclin b", "complex with cyclin b phosphorylates", "with cyclin b phosphorylates golga2", "b phosphorylates golga2 gm130", "golga2 gm130 and", "grasp65 constituents of", "constituents of a cis golgi", "of a cis golgi membrane", "a cis golgi membrane complex", "golgi membrane complex lowe", "membrane complex lowe et", "complex lowe et al.", "et al. 1998 preisinger", "al. 1998 preisinger et", "1998 preisinger et al.", "preisinger et al. 2005 .", "et al. 2005 . phosphorylation", "al. 2005 . phosphorylation of", "2005 . phosphorylation of golga2", ". phosphorylation of golga2 prevents", "phosphorylation of golga2 prevents binding", "of golga2 prevents binding of", "golga2 prevents binding of uso1", "binding of uso1 p115", "p115 a protein", "a protein localizing to the", "protein localizing to the membrane", "localizing to the membrane of", "to the membrane of er", "membrane of er endoplasmic", "of er endoplasmic reticulum", "endoplasmic reticulum to golgi", "reticulum to golgi transport", "to golgi transport vesicles and", "golgi transport vesicles and cis", "transport vesicles and cis golgi", "and cis golgi thereby", "cis golgi thereby impairing", "golgi thereby impairing fusion", "thereby impairing fusion of these", "impairing fusion of these vesicles", "fusion of these vesicles with", "of these vesicles with cis", "these vesicles with cis golgi", "vesicles with cis golgi cisternae", "with cis golgi cisternae and", "cis golgi cisternae and stopping", "golgi cisternae and stopping er", "cisternae and stopping er to", "and stopping er to golgi", "stopping er to golgi transport", "to golgi transport lowe", "golgi transport lowe et", "transport lowe et al.", "et al. 1998 seeman", "al. 1998 seeman et", "1998 seeman et al.", "et al. 2000 moyer", "al. 2000 moyer et", "2000 moyer et al.", "moyer et al. 2001 .", "et al. 2001 . phosphorylation", "al. 2001 . phosphorylation of", "2001 . phosphorylation of gorasp1", ". phosphorylation of gorasp1 by", "phosphorylation of gorasp1 by cdk1", "of gorasp1 by cdk1 enables", "gorasp1 by cdk1 enables further", "by cdk1 enables further phosphorylation", "cdk1 enables further phosphorylation of", "enables further phosphorylation of gorasp1", "further phosphorylation of gorasp1 by", "phosphorylation of gorasp1 by plk1", "gorasp1 by plk1 sutterlin", "by plk1 sutterlin et", "plk1 sutterlin et al.", "et al. 2001 preisinger", "al. 2001 preisinger et", "2001 preisinger et al.", "2005 . phosphorylation of gorasp1", "of gorasp1 by cdk1 and", "gorasp1 by cdk1 and plk1", "by cdk1 and plk1 impairs", "cdk1 and plk1 impairs stacking", "and plk1 impairs stacking of", "plk1 impairs stacking of golgi", "impairs stacking of golgi cisternae", "stacking of golgi cisternae by", "of golgi cisternae by interfering", "golgi cisternae by interfering with", "cisternae by interfering with formation", "by interfering with formation of", "interfering with formation of gorasp1", "with formation of gorasp1 trans", "formation of gorasp1 trans oligomers", "of gorasp1 trans oligomers that", "gorasp1 trans oligomers that would", "trans oligomers that would normally", "oligomers that would normally link", "that would normally link the", "would normally link the golgi", "normally link the golgi cisternae", "link the golgi cisternae together", "golgi cisternae together wang", "cisternae together wang et", "together wang et al.", "et al. 2003 wang", "al. 2003 wang et", "2003 wang et al.", "et al. 2005 sengupta", "al. 2005 sengupta and", "2005 sengupta and linstedt", "sengupta and linstedt 2010 .", "and linstedt 2010 .

", "linstedt 2010 .

in", "2010 .

in the", ".

in the median", "

in the median golgi", "the median golgi gorasp2", "golgi gorasp2 grasp55", "grasp55 a protein", "a protein that forms a", "protein that forms a complex", "that forms a complex with", "forms a complex with blfz1", "complex with blfz1 golgin", "with blfz1 golgin 45", "golgin 45 and rab2a", "45 and rab2a gtpase", "and rab2a gtpase and contributes", "rab2a gtpase and contributes to", "gtpase and contributes to cisternae", "and contributes to cisternae stacking", "contributes to cisternae stacking and", "to cisternae stacking and golgi", "cisternae stacking and golgi trafficking", "and golgi trafficking short", "golgi trafficking short et", "trafficking short et al.", "al. 2001 is", "2001 is also", "is also phosphorylated in mitosis.", "also phosphorylated in mitosis. phosphorylation", "phosphorylated in mitosis. phosphorylation of", "in mitosis. phosphorylation of gorasp2", "mitosis. phosphorylation of gorasp2 by", "phosphorylation of gorasp2 by mek1/2", "of gorasp2 by mek1/2 activated", "gorasp2 by mek1/2 activated mapk1", "mek1/2 activated mapk1 erk2", "mapk1 erk2 and/or", "erk2 and/or mapk3 3", "and/or mapk3 3 erk1b", "mapk3 3 erk1b in", "3 erk1b in human", "erk1b in human erk1c", "in human erk1c in", "human erk1c in rat", "erk1c in rat contributes", "in rat contributes to", "rat contributes to golgi", "contributes to golgi unlinking in", "to golgi unlinking in g2", "golgi unlinking in g2 and", "unlinking in g2 and fragmentation", "in g2 and fragmentation of", "g2 and fragmentation of golgi", "and fragmentation of golgi cisternae", "fragmentation of golgi cisternae in", "of golgi cisternae in mitotic", "golgi cisternae in mitotic prophase", "in mitotic prophase acharya", "mitotic prophase acharya et", "prophase acharya et al.", "et al. 1998 jesch", "al. 1998 jesch et", "1998 jesch et al.", "et al. 2001 colanzi", "al. 2001 colanzi et", "2001 colanzi et al.", "et al. 2003 shaul", "al. 2003 shaul and", "2003 shaul and seger", "and seger 2006 duran", "seger 2006 duran et", "2006 duran et al.", "et al. 2008 feinstein", "al. 2008 feinstein and", "2008 feinstein and linstedt", "and linstedt 2007 feinstein", "linstedt 2007 feinstein and", "2007 feinstein and linstedt", "and linstedt 2008 xiang", "linstedt 2008 xiang and", "2008 xiang and wang", "xiang and wang 2010 ." ] }, { "record_id": "GLY_000594_1_786", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162699", "r hsa", "hsa 162699", "r hsa 162699" ] }, { "record_id": "GLY_000594_1_786", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of dolichyl", "dolichyl phosphate", "phosphate mannose", "synthesis of dolichyl", "of dolichyl phosphate", "dolichyl phosphate mannose", "synthesis of dolichyl phosphate", "of dolichyl phosphate mannose", "synthesis of dolichyl phosphate mannose", "is the", "the donor", "donor of", "of mannose", "mannose groups", "groups in", "in the", "the synthesis", "of the", 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the steps of", "independently.

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"allowed the definition of", "the definition of complementation", "definition of complementation groups", "of complementation groups corresponding", "complementation groups corresponding to", "groups corresponding to distinct", "corresponding to distinct mutated", "to distinct mutated genes", "mutated genes and", "genes and cdnas", "and cdnas corresponding to", "cdnas corresponding to normal", "corresponding to normal forms", "to normal forms of", "normal forms of these", "forms of these genes", "of these genes were", "these genes were identified", "genes were identified on", "were identified on the", "identified on the basis", "on the basis of", "the basis of their", "basis of their abilities", "of their abilities to", "their abilities to restore", "abilities to restore normal", "to restore normal cell", "restore normal cell surface", "normal cell surface protein", "cell surface protein expression", "surface protein expression in", "protein expression in mutant", "expression in mutant cells.", "in mutant cells. co", "mutant cells. co precipitation", "cells. co precipitation experiments", "co precipitation experiments with", "precipitation experiments with tagged", "experiments with tagged cloned", "with tagged cloned proteins", "tagged cloned proteins have", "cloned proteins have allowed", "proteins have allowed the", "have allowed the identification", "allowed the identification of", "the identification of additional", "identification of additional proteins", "of additional proteins involved", "additional proteins involved in", "proteins involved in gpi", "involved in gpi anchor", "in gpi anchor biosynthesis.", "inositol gpi acts", "gpi acts as a", "acts as a membrane anchor", "as a membrane anchor for", "a membrane anchor for many", "membrane anchor for many cell", "anchor for many cell surface", "for many cell surface proteins.", "many cell surface proteins. gpi", "cell surface proteins. gpi is", "surface proteins. gpi is synthesized", "proteins. gpi is synthesized in", "gpi is synthesized in the", "is synthesized in the endoplasmic", "synthesized in the endoplasmic reticulum.", "in the endoplasmic reticulum. in", "the endoplasmic reticulum. in humans", "reticulum. in humans a", "in humans a single", "humans a single pathway", "a single pathway consisting of", "single pathway consisting of nine", "pathway consisting of nine reactions", "consisting of nine reactions appears", "of nine reactions appears to", "nine reactions appears to be", "reactions appears to be responsible", "appears to be responsible for", "to be responsible for the", "be responsible for the synthesis", "responsible for the synthesis of", "for the synthesis of the", "the synthesis of the major", "synthesis of the major gpi", "of the major gpi species", "the major gpi species involved", "major gpi species involved in", "gpi species involved in membrane", "species involved in membrane protein", "involved in membrane protein anchoring.", "in membrane protein anchoring. this", "membrane protein anchoring. this pathway", "protein anchoring. this pathway is", "anchoring. this pathway is shown", "this pathway is shown in", "pathway is shown in the", "is shown in the figure.", "shown in the figure. two", "in the figure. two additional", "the figure. two additional reactions", "two additional reactions not", "additional reactions not shown", "shown allow the", "allow the synthesis of", "the synthesis of variant forms", "synthesis of variant forms of", "of variant forms of gpi", "forms of gpi one", "of gpi one with", "gpi one with an", "one with an additional mannose", "with an additional mannose residue", "an additional mannose residue and", "additional mannose residue and one", "mannose residue and one with", "residue and one with an", "and one with an additional", "one with an additional ethanolamine", "an additional ethanolamine tauron", "additional ethanolamine tauron et", "ethanolamine tauron et al.", "et al. 2004 shishioh", "al. 2004 shishioh et", "2004 shishioh et al.", "shishioh et al. 2005 .", "et al. 2005 . these", "al. 2005 . these variant", "2005 . these variant gpi", ". these variant gpi molecules", "these variant gpi molecules may", "variant gpi molecules may be", "gpi molecules may be used", "molecules may be used for", "may be used for tissue", "be used for tissue specific", "used for tissue specific protein", "for tissue specific protein modifications", "specific protein modifications or", "protein modifications or may", "modifications or may function", "or may function independently.

the steps", "may function independently.

the steps of", "function independently.

the steps of gpi", "independently.

the steps of gpi synthesis", "steps of gpi synthesis were", "of gpi synthesis were first", "gpi synthesis were first identified", "synthesis were first identified by", "were first identified by isolating", "first identified by isolating large", "identified by isolating large numbers", "by isolating large numbers of", "isolating large numbers of mutant", "large numbers of mutant cell", "numbers of mutant cell lines", "of mutant cell lines that", "mutant cell lines that had", "cell lines that had lost", "lines that had lost the", "that had lost the ability", "had lost the ability to", "lost the ability to express", "the ability to express gpi", "ability to express gpi anchored", "to express gpi anchored proteins", "express gpi anchored proteins on", "gpi anchored proteins on their", "anchored proteins on their surfaces.", "proteins on their surfaces. somatic", "on their surfaces. somatic cell", "their surfaces. somatic cell hybrid", "surfaces. somatic cell hybrid analyses", "somatic cell hybrid analyses of", "cell hybrid analyses of these", "hybrid analyses of these lines", "analyses of these lines allowed", "of these lines allowed the", "these lines allowed the definition", "lines allowed the definition of", "allowed the definition of complementation", "the definition of complementation groups", "definition of complementation groups corresponding", "of complementation groups corresponding to", "complementation groups corresponding to distinct", "groups corresponding to distinct mutated", "corresponding to distinct mutated genes", "distinct mutated genes and", "mutated genes and cdnas", "genes and cdnas corresponding", "and cdnas corresponding to normal", "cdnas corresponding to normal forms", "corresponding to normal forms of", "to normal forms of these", "normal forms of these genes", "forms of these genes were", "of these genes were identified", "these genes were identified on", "genes were identified on the", "were identified on the basis", "identified on the basis of", "on the basis of their", "the basis of their abilities", "basis of their abilities to", "of their abilities to restore", "their abilities to restore normal", "abilities to restore normal cell", "to restore normal cell surface", "restore normal cell surface protein", "normal cell surface protein expression", "cell surface protein expression in", "surface protein expression in mutant", "protein expression in mutant cells.", "expression in mutant cells. co", "in mutant cells. co precipitation", "mutant cells. co precipitation experiments", "cells. co precipitation experiments with", "co precipitation experiments with tagged", "precipitation experiments with tagged cloned", "experiments with tagged cloned proteins", "with tagged cloned proteins have", "tagged cloned proteins have allowed", "cloned proteins have allowed the", "proteins have allowed the identification", "have allowed the identification of", "allowed the identification of additional", "the identification of additional proteins", "identification of additional proteins involved", "of additional proteins involved in", "additional proteins involved in gpi", "proteins involved in gpi anchor", "involved in gpi anchor biosynthesis." ] }, { "record_id": "GLY_000594_1_788", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162791", "r hsa", "hsa 162791", "r hsa 162791" ] }, { "record_id": "GLY_000594_1_788", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "attachment of", "of gpi", "gpi anchor", "anchor to", "to upar", "attachment of gpi", "of gpi anchor", "gpi anchor to", "anchor to upar", "attachment of gpi anchor", "of gpi anchor to", "gpi anchor to upar", "attachment of gpi anchor to", "of gpi anchor to upar", "the mature", "mature form", "form of", "of urokinase", "urokinase plasminogen", "plasminogen activator", "activator receptor", "is attached", "attached to", "to the", "the plasma", "plasma membrane", 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attached to", "is attached to the plasma", "attached to the plasma membrane", "to the plasma membrane by", "the plasma membrane by a", "plasma membrane by a glycosylphosphatidylinositol", "by a glycosylphosphatidylinositol gpi", "glycosylphosphatidylinositol gpi anchor", "gpi anchor ploug", "anchor ploug et al.", "ploug et al. 1991 .", "et al. 1991 . as", "al. 1991 . as nascent", "1991 . as nascent upar", ". as nascent upar polypeptide", "as nascent upar polypeptide moves", "nascent upar polypeptide moves into", "upar polypeptide moves into the", "polypeptide moves into the lumen", "moves into the lumen of", "into the lumen of the", "the lumen of the endoplasmic", "lumen of the endoplasmic reticulum", "the endoplasmic reticulum it", "endoplasmic reticulum it is", "reticulum it is attacked", "it is attacked by a", "is attacked by a transamidase", "attacked by a transamidase complex", "by a transamidase complex that", "a transamidase complex that cleaves", "transamidase complex that 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the", ".
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mutations", "

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the mechanism", ".
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mutations in", "

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the", "2011 .
the mechanism of", ".
the mechanism of atp", "mechanism of atp synthesis", "of atp synthesis by", "atp synthesis by complex", "synthesis by complex v", "by complex v was", "complex v was predicted", "v was predicted by", "was predicted by boyer", "predicted by boyer et", "by boyer et al", "boyer et al in", "et al in 1973:", "al in 1973: adp", "in 1973: adp and", "1973: adp and pi", "adp and pi bind", "and pi bind to", "pi bind to the", "bind to the enzyme", "to the enzyme resulting", "the enzyme resulting in", "enzyme resulting in a", "resulting in a conformational", "in a conformational change.", "a conformational change. atp", "conformational change. atp is", "change. atp is then", "atp is then synthesized", "then synthesized still", "synthesized still bound", "still bound to the", "bound to the enzyme.", "to the enzyme. another", "the enzyme. another change", "enzyme. another change in", "another change in the", "change in the active", "in the active site", "the active site results", "active site results in", "site results in the", "results in the release", "in the release of", "the release of free", "release of free atp", "of free atp into", "free atp into the", "atp into the matrix.", "into the matrix. the", "the matrix. the overall", "matrix. the overall reaction", "the overall reaction is:
adp", "overall reaction is:
adp +", "reaction is:
adp + pi", "is:
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mutations", "matrix

mutations in several", "

mutations in several atp", "in several atp synthase", "several atp synthase subunits", "atp synthase subunits can", "synthase subunits can lead", "subunits can lead to", "can lead to different", "lead to different types", "to different types of", "different types of mitochondrial", "types of mitochondrial complex", "of mitochondrial complex v", "mitochondrial complex v deficiency", "v deficiency mc5d", "mc5d reviewed in", "reviewed in garone et", "in garone et al.", "et al. 2022", "2022 del dotto", "del dotto et al.", "et al. 2024", "al. 2024 .", "the re entry of protons", "re entry of protons into", "entry of protons into the", "of protons into the mitochondrial", "protons into the mitochondrial matrix", "into the mitochondrial matrix through", "the mitochondrial matrix through complex", "mitochondrial matrix through complex v", "matrix through complex v causes", "through complex v causes conformational", "complex v causes conformational changes", "v causes conformational changes which", "causes conformational changes which result", "conformational changes which result in", "changes which result in atp", "which result in atp synthesis.", "result in atp synthesis. complex", "in atp synthesis. complex v", "synthesis. complex v atp", "complex v atp synthase", "atp synthase is composed", "synthase is composed of", "is composed of 3 parts", "of 3 parts an", "3 parts an f1", "parts an f1 catalytic", "f1 catalytic core approx", "catalytic core approx 5", "core approx 5 subunits", "5 subunits an", "subunits an f0", "an f0 membrane proton channel", "membrane proton channel approx", "proton channel approx 9", "channel approx 9 subunits", "approx 9 subunits and", "9 subunits and two", "subunits and two stalks", "and two stalks linking f1", "two stalks linking f1 to", "stalks linking f1 to f0.", "linking f1 to f0. f1", "f1 to f0. f1 contains", "to f0. f1 contains three", "f0. f1 contains three alpha", "f1 contains three alpha subunits", "three alpha subunits three", "alpha subunits three beta", "subunits three beta subunits", "three beta subunits and", "beta subunits and one", "subunits and one each", "and one each of gamma", "each of gamma delta", "gamma delta and", "delta and epsilon subunits.", "and epsilon subunits. each beta", "epsilon subunits. each beta subunit", "subunits. each beta subunit contains", "each beta subunit contains an", "beta subunit contains an active", "subunit contains an active site", "contains an active site for", "an active site for atp", "active site for atp synthesis.", "site for atp synthesis. f0", "for atp synthesis. f0 has", "atp synthesis. f0 has at", "synthesis. f0 has at least", "f0 has at least 9", "has at least 9 subunits", "least 9 subunits a", "9 subunits a g", "a g a6l and", "g a6l and f6", "a6l and f6 see", "and f6 see lai", "f6 see lai et", "lai et al. 2023", "al. 2023 reviewed", "2023 reviewed in jonckheere", "reviewed in jonckheere et al.", "jonckheere et al. 2011", "et al. 2011 .
the", "al. 2011 .
the mechanism", "2011 .
the mechanism of atp", ".
the mechanism of atp synthesis", "mechanism of atp synthesis by", "of atp synthesis by complex", "atp synthesis by complex v", "synthesis by complex v was", "by complex v was predicted", "complex v was predicted by", "v was predicted by boyer", "was predicted by boyer et", "predicted by boyer et al", "by boyer et al in", "boyer et al in 1973:", "et al in 1973: adp", "al in 1973: adp and", "in 1973: adp and pi", "1973: adp and pi bind", "adp and pi bind to", "and pi bind to the", "pi bind to the enzyme", "bind to the enzyme resulting", "to the enzyme resulting in", "the enzyme resulting in a", "enzyme resulting in a conformational", "resulting in a conformational change.", "in a conformational change. atp", "a conformational change. atp is", "conformational change. atp is then", "change. atp is then synthesized", "is then synthesized still", "then synthesized still bound", "synthesized still bound to", "still bound to the enzyme.", "bound to the enzyme. another", "to the enzyme. another change", "the enzyme. another change in", "enzyme. another change in the", "another change in the active", "change in the active site", "in the active site results", "the active site results in", "active site results in the", "site results in the release", "results in the release of", "in the release of free", "the release of free atp", "release of free atp into", "of free atp into the", "free atp into the matrix.", "atp into the matrix. the", "into the matrix. the overall", "the matrix. the overall reaction", "matrix. the overall reaction is:
adp", "the overall reaction is:
adp +", "overall reaction is:
adp + pi", "reaction is:
adp + pi +", "is:
adp + pi + h+", "+ pi + h+ +", "pi + h+ + nh+", "h+ + nh+ intermemb.", "+ nh+ intermemb. space", "intermemb. space = atp", "space = atp +", "= atp + h2o +", "atp + h2o + nh+", "h2o + nh+ matrix", "+ nh+ matrix

mutations", "nh+ matrix

mutations in", "matrix

mutations in several atp", "

mutations in several atp synthase", "in several atp synthase subunits", "several atp synthase subunits can", "atp synthase subunits can lead", "synthase subunits can lead to", "subunits can lead to different", "can lead to different types", "lead to different types of", "to different types of mitochondrial", "different types of mitochondrial complex", "types of mitochondrial complex v", "of mitochondrial complex v deficiency", "complex v deficiency mc5d", "deficiency mc5d reviewed", "mc5d reviewed in garone", "reviewed in garone et al.", "garone et al. 2022", "al. 2022 del", "2022 del dotto et", "dotto et al. 2024", "et al. 2024 ." ] }, { "record_id": "GLY_000594_1_790", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1632852", "r hsa", "hsa 1632852", "r hsa 1632852" ] }, { "record_id": "GLY_000594_1_790", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hereafter referred", "referred to", "to as", "as autophagy", "acts as", "as a", "a buffer", "buffer against", "against starvation", "starvation by", "by liberating", "liberating building", "building materials", "materials and", "and energy", "energy sources", "sources from", "from cellular", "cellular components.", "components. it", "it has", "has additional", "additional roles", "roles in", "in embryonic", "embryonic development", "removal of", "of apoptotic", "apoptotic cells", "cells or", "or organelles", "antigen presentation", "protection against", "against toxins", "toxins and", "and as", "a degradation", "degradation route", "route for", "for aggregate", "aggregate prone", "prone proteins", "proteins and", "and infectious", "infectious agents.", "agents. the", "the dysregulation", "dysregulation of", "of autophagy", "autophagy is", "is involved", "involved in", "in several", "several human", "human diseases", "for example", "crohn's disease", "cancer and", "and neurodegeneration", "ravikumar et", "et al.", "al. 2010", "2010 .
autophagy", ".
autophagy is", "is highly", "highly conserved", "conserved from", "from yeast", "yeast to", "to humans", "much of", "of the", "the machinery", "machinery was", "was first", "first identified", "identified in", "in yeast", "see klionsky", "klionsky et", "al. 2011", "2011 .", ". initially", "double membraned", "membraned cup", "cup shaped", "shaped structures", "structures called", "called the", "the isolation", "isolation membrane", "membrane or", "or phagophore", "phagophore engulf", "engulf portions", "portions of", "of cytoplasm.", "cytoplasm. the", "the membranes", "membranes fuse", "fuse to", "to form", "form the", "the autophagosome.", "autophagosome. in", "yeast cells", "autophagosomes are", "are formed", "formed at", "at the", "the phagophore", "phagophore assembly", "assembly site", "next to", "to the", "the vacuole.", "vacuole. in", "in mammals", "autophagosomes appear", "appear throughout", "throughout the", "the cytoplasm", "cytoplasm then", "then move", "move along", "along microtubules", "microtubules towards", "towards the", "the microtubule", "microtubule organising", "organising centre.", "centre. this", "this transport", "transport requires", "requires microtubules", "microtubules and", "and the", "the function", "function of", "of dynein", "dynein motor", "motor proteins", "depolymerization of", "of microtubules", "microtubules or", "or inhibition", "inhibition of", "dynein dependent", "dependent transport", "transport results", "results in", "in inhibition", "kochl et", "al. 2006", "kimura et", "al. 2008", "2008 .", ". autophagosomes", "autophagosomes fuse", "fuse with", "with lysosomes", "lysosomes forming", "forming autolysosomes", "autolysosomes whose", "whose contents", "contents are", "are degraded", "degraded by", "by lysosomal", "lysosomal hydrolases", "mizushima et", "2011 .

the", ".

the origins", "origins of", "the autophagosomal", "autophagosomal membrane", "membrane and", "incorporation of", "of existing", "existing membrane", "membrane material", "material have", "have been", "been extensively", "extensively debated.", "debated. the", "the endoplasmic", "endoplasmic reticulum", "mitochondria associated", "associated er", "er membranes", "the golgi", "the plasma", "plasma membrane", "and recycling", "recycling endosomes", "endosomes have", "have all", "all been", "been implicated", "implicated in", "in the", "the nucleation", "nucleation of", "and subsequent", "subsequent growth", "growth of", "the membrane", "lamb et", "al. 2013", "2013 .", ". recently", "recently 3d", "3d tomographic", "tomographic imaging", "imaging of", "of isolation", "isolation membranes", "membranes has", "has shown", "shown the", "the cup", "shaped isolation", "membrane tightly", "tightly sandwiched", "sandwiched between", "between two", "two sheets", "sheets of", "of er", "er and", "and physically", "physically connected", "connected to", "the er", "er through", "through a", "a narrow", "narrow membrane", "membrane tube", "hayashi nishino", "nishino et", "al. 2009", "yla anttila", "anttila et", "2009 .", ". this", "this suggests", "suggests that", "that isolation", "membrane formation", "formation and", "and elongation", "elongation are", "are guided", "guided by", "by adjacent", "adjacent er", "er sheets", "supporting the", "the now", "now prevalent", "prevalent 'er", "'er cradle'", "cradle' model", "which suggests", "that the", "membrane arises", "arises from", "from the", "shibutani &", "& yoshimori", "yoshimori 2014", "2014 .

autophagy", ".

autophagy is", "is tightly", "tightly regulated.", "regulated. the", "the induction", "induction of", "autophagy in", "in response", "response to", "to starvation", "starvation is", "is partly", "partly mediated", "mediated by", "by inactivation", "inactivation of", "the mammalian", "mammalian target", "target of", "of rapamycin", "noda &", "& ohsumi", "ohsumi 1998", "and activation", "activation of", "of jun", "jun n", "n terminal", "terminal kinase", "while energy", "energy loss", "loss induces", "induces autophagy", "autophagy by", "by activation", "of amp", "amp kinase", "ampk .", ". other", "other pathways", "pathways regulating", "regulating autophagy", "autophagy are", "are regulated", "regulated by", "by calcium", "cyclic amp", "calpains and", "the inositol", "inositol trisphosphate", "rubinsztein et", "al. 2012", "2012 .", ".

in", "

in mammals", "two complexes", "complexes cooperatively", "cooperatively produce", "produce the", "isolation membrane.", "membrane. the", "the ulk", "ulk complex", "complex consists", "consists of", "of ulk1/2", "and atg101", "alers et", ". the", "the pik3c3", "pik3c3 containing", "containing beclin", "beclin 1", "1 complex", "of pik3c3", "and atg14", "matsunaga et", "zhong et", ". a", "a similar", "similar complex", "complex where", "where atg14", "atg14 is", "is replaced", "replaced by", "by uvrag", "uvrag functions", "functions later", "later in", "in autophagosome", "autophagosome maturation", "maturation and", "and endocytic", "endocytic traffic", "itakura et", "liang et", ". binding", "binding of", "of kiaa0226", "kiaa0226 to", "to this", "this complex", "complex negatively", "negatively regulates", "regulates the", "the maturation", "maturation process", "ulk and", "and beclin", "1 complexes", "complexes are", "are recruited", "recruited to", "to specific", "specific autophagosome", "autophagosome nucleation", "nucleation regions", "regions where", "where they", "they stimulate", "stimulate phosphatidylinositol", "phosphatidylinositol 3", "3 phosphate", "production and", "and facilitate", "facilitate the", "the elongation", "elongation and", "and initial", "initial membrane", "membrane curvature", "curvature of", "phagophore membrane", "carlsson &", "& simonsen", "simonsen 2015", "2015 .

the", ".

the ulk", "complex is", "is considered", "considered the", "the most", "most upstream", "upstream component", "component of", "mammalian autophagy", "autophagy pathway", "itakura &", "& mizushima", "mizushima 2010", "acting as", "as an", "an integrator", "integrator of", "the autophagy", "autophagy signals", "signals downstream", "downstream of", "of mtorc1.", "mtorc1. it", "it is", "is not", "not fully", "fully understood", "understood how", "how ulk1", "ulk1 is", "is modulated", "modulated in", "to environmental", "environmental cues.", "cues. phosphorylation", "phosphorylation plays", "plays an", "an essential", "essential role", "dunlop &", "& tee", "tee 2013", "but it", "not clear", "clear how", "how phosphorylation", "phosphorylation regulates", "regulates ulk1", "ulk1 activities", "2010 .", ". ulk1", "ulk1 kinase", "kinase activity", "activity is", "is required", "required for", "for autophagy", "but the", "the substrate", "substrate s", "of ulk1", "ulk1 that", "that mediate", "mediate its", "its autophagic", "autophagic function", "function are", "are not", "not certain.", "certain. ulk1", "ulk1 may", "may also", "also have", "have kinase", "kinase independent", "independent functions", "functions in", "in autophagy", "wong et", ".

", "

pik3c3", "is a", "a class", "class iii", "iii phosphatidylinositol", "3 kinase", "kinase that", "that produces", "produces pi3p.", "pi3p. it", "is essential", "essential for", "for the", "the early", "early stages", "stages of", "autophagy and", "and colocalizes", "colocalizes strongly", "strongly with", "with early", "early autophagosome", "autophagosome markers", "axe et", ". becn1", "becn1 binds", "binds several", "several further", "further proteins", "proteins that", "that affect", "affect autophagosome", "autophagosome formation.", "formation. partners", "partners that", "that induce", "induce autophagy", "autophagy include", "include ambra1", "fimia et", "al. 2007", "and sh3glb1", "takahashi et", "2007 .", "of bcl2", "bcl2 or", "or bcl2l1", "bcl xl", "inhibit autophagy", "pattingre et", "al. 2005", "ciechomska et", "inositol 1", "1 4", "4 5", "5 trisphosphate", "trisphosphate receptor", "receptor complex", "complex that", "that binds", "binds bcl2", "bcl2 also", "also interacts", "interacts with", "with becn1", "inhibiting autophagy", "vincencio et", ". cisd2", "nutrient deprivation", "deprivation autophagy", "autophagy factor", "factor 1", "a component", "component in", "the ip3r", "ip3r complex", "with bcl2", "bcl2 at", "and stabilizes", "stabilizes the", "the bcl2", "bcl2 becn1", "becn1 interaction", "chang et", ". starvation", "starvation leads", "leads to", "to activation", "of c", "c jun", "jun nh2", "nh2 terminal", "kinase 1", "which results", "the phosphorylation", "phosphorylation of", "bcl2 and", "and bcl2l1", "which release", "release their", "their binding", "binding to", "to becn1", "becn1 and", "and thus", "thus induces", "induces autophagosome", "autophagosome formation", "wei et", ".

ambra1", "

ambra1 can", "can simultaneously", "simultaneously bind", "bind dynein", "dynein and", "the beclin", "1 complex.", "during nutrient", "nutrient starvation", "ambra1 is", "is phosphorylated", "phosphorylated in", "in a", "a ulk1", "ulk1 dependent", "dependent manner", "di bartolomeo", "bartolomeo et", "this phosphorylation", "phosphorylation releases", "releases ambra1", "ambra1 associated", "associated beclin", "complexes from", "from dynein", "microtubule network", "freeing the", "the complex", "complex to", "to translocate", "translocate to", "to autophagy", "autophagy initiation", "initiation sites", ".

a", "

a characteristic", "characteristic of", "of this", "this early", "early phase", "phase of", "of autophagosome", "formation is", "is the", "the formation", "formation of", "of pi3p", "pi3p enriched", "enriched er", "er associated", "associated structures", "called omegasomes", "or cradles", ". omegasomes", "omegasomes appear", "appear to", "to concentrate", "concentrate at", "at or", "or near", "near the", "the connected", "connected mitochondria", "er membrane", "hamasaki et", ". however", "phagophore also", "also can", "can incorporate", "incorporate existing", "existing material", "material from", "from other", "other membrane", "membrane sources", "sources such", "such as", "as er", "er exit", "exit sites", "er golgi", "golgi intermediate", "intermediate compartment", "2015 .", "omegasomes lead", "lead to", "which is", "is thought", "thought to", "form de", "de novo", "novo by", "by an", "an unknown", "unknown mechanism", "simonsen &", "& stenmark", "stenmark 2008", "roberts &", "& ktistakis", "ktistakis 2013", ". phagophore", "phagophore expansion", "expansion is", "is probably", "probably mediated", "by membrane", "membrane uptake", "uptake from", "from endomembranes", "endomembranes and", "and semi", "semi autonomous", "autonomous organelles", "2014 .

atg9", ".

atg9 is", "a direct", "direct target", "of ulk1.", "ulk1. in", "in nutrient", "nutrient rich", "rich conditions", "conditions mammalian", "mammalian atg9", "atg9 is", "is localized", "localized to", "the trans", "trans golgi", "golgi network", "network and", "and endosomes", "including early", "late and", "whereas under", "under starvation", "starvation conditions", "conditions it", "to autophagosomes", "a process", "process that", "that is", "is dependent", "dependent on", "on ulk1", "young et", "2006 .", ". atg9", "is believed", "believed to", "to play", "play a", "a role", "role in", "the delivery", "delivery of", "of vesicles", "vesicles derived", "derived from", "from existing", "existing membranes", "membranes to", "the expanding", "expanding phagophore", ". yeast", "yeast atg9", "atg9 forms", "forms a", "a complex", "complex with", "with atg2", "atg2 and", "and atg18", "reggiori et", "al. 2004", "2004 .", ".

pi3p", "

pi3p produced", "produced at", "the initiation", "initiation site", "site is", "is sensed", "sensed by", "by wipi2b", "mammalian homologue", "homologue of", "of atg18", "polson et", ". wipi2b", "wipi2b then", "then recruits", "recruits atg16l1", "dooley et", "al. 2014", "2014 .", ". there", "there are", "are four", "four wipi", "wipi proteins", "proteins in", "in mammalian", "mammalian cells", "proikas cezanne", "cezanne et", "al. 2015", ". they", "they are", "are all", "all likely", "likely bind", "bind pi3p", "pi3p and", "and be", "be recruited", "to membranes", "membranes but", "of wipi1", "3 and", "and 4", "4 in", "not yet", "yet clear.", "clear. wipi4", "has been", "been shown", "shown to", "to bind", "bind atg2", "and to", "to be", "be involved", "in lipid", "lipid droplet", "droplet formation", "velikkakath et", "mutations in", "in wipi4", "wipi4 have", "to cause", "cause a", "a neurodegenerative", "neurodegenerative disease", "saitsu et", "2013 .

the", ".

the elongation", "elongation of", "membrane that", "that will", "will become", "become the", "the autophagosome", "autophagosome is", "is regulated", "by two", "two ubiquitination", "ubiquitination like", "like reactions.", "reactions. first", "the ubiquitin", "ubiquitin like", "like molecule", "molecule atg12", "atg12 is", "is conjugated", "conjugated to", "to atg5", "atg5 by", "by atg7", "which acts", "an e1", "e1 like", "like activating", "activating enzyme", "and atg10", "which has", "has a", "role similar", "similar to", "to an", "an e2", "e2 ubiquitin", "ubiquitin conjugating", "conjugating enzyme.", "enzyme. the", "the atg5:atg12", "atg5:atg12 complex", "complex then", "then interacts", "interacts non", "non covalently", "covalently with", "with atg16l1.", "atg16l1. this", "complex associates", "associates with", "with the", "the forming", "forming autophagosome", "autophagosome but", "but dissociates", "dissociates from", "from completed", "completed autophagosomes", "geng &", "& klionski", "klionski 2008", "the second", "second ubiquitin", "like reaction", "reaction involves", "involves the", "the conjugation", "conjugation of", "of ubiquitin", "like molecules", "molecules of", "the lc3", "lc3 family", "weidberg et", ". lc3", "lc3 proteins", "proteins are", "are conjugated", "conjugated through", "through their", "their c", "c terminal", "terminal glycine", "glycine residues", "residues with", "with pe", "pe by", "by the", "the e1", "like atg7", "atg7 and", "and e2", "e2 like", "like atg3.", "atg3. this", "this allows", "allows lc3", "proteins to", "to associate", "associate with", "autophagosome membrane.", "membrane.

the", "

the atg12:atg5:atg16l1", "atg12:atg5:atg16l1 complex", "an e3", "e3 like", "like enzyme", "enzyme for", "of lc3", "family proteins", "mammalian homologues", "homologues of", "of yeast", "yeast atg8", "to phosphatidylethanolamine", "hanada et", "fujita et", "lc3 pe", "pe can", "can be", "be deconjugated", "deconjugated by", "the protease", "protease atg4", "li et", ". atg4", "atg4 is", "is also", "also responsible", "responsible for", "for priming", "priming lc3", "proteins by", "by cleaving", "cleaving the", "the c", "c terminus", "terminus to", "to expose", "expose a", "a glycine", "glycine residue", "kirisako et", "et al", "scherz shouval", "shouval et", "proteins remain", "remain associated", "associated with", "with autophagosomes", "autophagosomes until", "until they", "they fuse", "with lysosomes.", "lysosomes. the", "lc3 like", "like proteins", "proteins inside", "inside the", "the resulting", "resulting autolysosomes", "autolysosomes are", "while those", "those on", "on the", "the cytoplasmic", "cytoplasmic surface", "surface are", "are delipidated", "delipidated and", "and recycled.", "recycled. atg5:atg12:atg16l1", "atg5:atg12:atg16l1 positive", "positive lc3", "lc3 negative", "negative vesicles", "vesicles represent", "represent pre", "pre autophagosomal", "autophagosomal structures", "pre phagophores", "phagophores and", "and possibly", "possibly early", "early phagophores", "lc3 positive", "positive structures", "structures can", "be considered", "considered to", "be phagophores", "and atg5:atg12:atg16l1", "atg5:atg12:atg16l1 negative", "negative lc3", "positive vesicles", "vesicles can", "be regarded", "regarded as", "as mature", "mature autophagosomes", "tandia et", "2011 .

phagophore", ".

phagophore expansion", "endomembranes as", "as well", "well as", "as from", "from semiautonomous", "semiautonomous organelles", "2014 .

the", ".

the mechanisms", "mechanisms involved", "the closure", "closure of", "membrane are", "are poorly", "poorly understood.", "understood. as", "as the", "phagophore is", "a double", "membraned structure", "its closure", "closure involves", "the fusion", "fusion of", "of a", "narrow opening", "is distinct", "distinct from", "membrane fusion", "fusion events", "the topology", "topology of", "is similar", "to that", "that of", "of cytokinesis", "viral budding", "budding or", "or multivesicular", "multivesicular body", "formation. these", "these processes", "processes rely", "rely on", "the endosomal", "endosomal sorting", "sorting complex", "complex required", "for transport", "rusten et", ". escrt", "escrt and", "and associated", "associated proteins", "proteins facilitate", "facilitate membrane", "membrane budding", "budding away", "away from", "the cytosol", "cytosol and", "subsequent cleavage", "cleavage of", "the bud", "bud neck", "hurley &", "& hanson", "hanson 2010", ". several", "several studies", "studies have", "have shown", "shown that", "that depletion", "depletion of", "of escrt", "escrt subunits", "subunits or", "or the", "the regulatory", "regulatory atpase", "atpase vps4", "vps4 causes", "causes an", "an accumulation", "accumulation of", "of autophagosomes", "filimonenko et", "clear whether", "whether escrts", "escrts are", "are required", "for autophagosome", "autophagosome closure", "closure or", "or for", "autophagosome to", "to endosome", "endosome fusion.", "fusion. uvrag", "uvrag is", "also involved", "maturation step", "recruiting proteins", "that bring", "bring about", "about membrane", "fusion such", "the class", "class c", "c vps", "vps proteins", "which activate", "activate rab7", "rab7 thereby", "thereby promoting", "promoting fusion", "fusion with", "with late", "late endosomes", "endosomes and", "and lysosomes", "macroautophagy hereafter", "hereafter referred to", "referred to as", "to as autophagy", "autophagy acts", "acts as a", "as a buffer", "a buffer against", "buffer against starvation", "against starvation by", "starvation by liberating", "by liberating building", "liberating building materials", "building materials and", "materials and energy", "and energy sources", "energy sources from", "sources from cellular", "from cellular components.", "cellular components. it", "components. it has", "it has additional", "has additional roles", "additional roles in", "roles in embryonic", "in embryonic development", "development removal", "removal of apoptotic", "of apoptotic cells", "apoptotic cells or", "cells or organelles", "organelles antigen", "presentation protection", "protection against toxins", "against toxins and", "toxins and as", "and as a", "as a degradation", "a degradation route", "degradation route for", "route for aggregate", "for aggregate prone", "aggregate prone proteins", "prone proteins and", "proteins and infectious", "and infectious agents.", "infectious agents. the", "agents. the dysregulation", "the dysregulation of", "dysregulation of autophagy", "of autophagy is", "autophagy is involved", "is involved in", "involved in several", "in several human", "several human diseases", "diseases for", "example crohn's", "disease cancer", "cancer and neurodegeneration", "neurodegeneration ravikumar", "ravikumar et al.", "et al. 2010", "al. 2010 .
autophagy", "2010 .
autophagy is", ".
autophagy is highly", "is highly conserved", "highly conserved from", "conserved from yeast", "from yeast to", "yeast to humans", "humans much", "much of the", "of the machinery", "the machinery was", "machinery was first", "was first identified", "first identified in", "identified in yeast", "yeast see", "see klionsky et", "klionsky et al.", "et al. 2011", "al. 2011 .", "2011 . initially", "initially double", "double membraned cup", "membraned cup shaped", "cup shaped structures", "shaped structures called", "structures called the", "called the isolation", "the isolation membrane", "isolation membrane or", "membrane or phagophore", "or phagophore engulf", "phagophore engulf portions", "engulf portions of", "portions of cytoplasm.", "of cytoplasm. the", "cytoplasm. the membranes", "the membranes fuse", "membranes fuse to", "fuse to form", "to form the", "form the autophagosome.", "the autophagosome. in", "autophagosome. in yeast", "in yeast cells", "cells autophagosomes", "autophagosomes are formed", "are formed at", "formed at the", "at the phagophore", "the phagophore assembly", "phagophore assembly site", "site pas", "pas next", "next to the", "to the vacuole.", "the vacuole. in", "vacuole. in mammals", "mammals autophagosomes", "autophagosomes appear throughout", "appear throughout the", "throughout the cytoplasm", "the cytoplasm then", "cytoplasm then move", "then move along", "move along microtubules", "along microtubules towards", "microtubules towards the", "towards the microtubule", "the microtubule organising", "microtubule organising centre.", "organising centre. this", "centre. this transport", "this transport requires", "transport requires microtubules", "requires microtubules and", "microtubules and the", "and the function", "the function of", "function of dynein", "of dynein motor", "dynein motor proteins", "proteins depolymerization", "depolymerization of microtubules", "of microtubules or", "microtubules or inhibition", "or inhibition of", "inhibition of dynein", "of dynein dependent", "dynein dependent transport", "dependent transport results", "transport results in", "results in inhibition", "in inhibition of", "inhibition of autophagy", "autophagy kochl", "kochl et al.", "et al. 2006", "2006 kimura", "kimura et al.", "et al. 2008", "al. 2008 .", "2008 . autophagosomes", ". autophagosomes fuse", "autophagosomes fuse with", "fuse with lysosomes", "with lysosomes forming", "lysosomes forming autolysosomes", "forming autolysosomes whose", "autolysosomes whose contents", "whose contents are", "contents are degraded", "are degraded by", "degraded by lysosomal", "by lysosomal hydrolases", "hydrolases mizushima", "mizushima et al.", "al. 2011 .

the", "2011 .

the origins", ".

the origins of", "origins of the", "of the autophagosomal", "the autophagosomal membrane", "autophagosomal membrane and", "membrane and the", "the incorporation", "incorporation of existing", "of existing membrane", "existing membrane material", "membrane material have", "material have been", "have been extensively", "been extensively debated.", "extensively debated. the", "debated. the endoplasmic", "the endoplasmic reticulum", "reticulum er", "mitochondria mitochondria", "mitochondria associated er", "associated er membranes", "membranes mams", "golgi the", "the plasma membrane", "plasma membrane and", "membrane and recycling", "and recycling endosomes", "recycling endosomes have", "endosomes have all", "have all been", "all been implicated", "been implicated in", "implicated in the", "in the nucleation", "the nucleation of", "nucleation of the", "of the isolation", "isolation membrane and", "membrane and subsequent", "and subsequent growth", "subsequent growth of", "growth of the", "of the membrane", "membrane lamb", "lamb et al.", "et al. 2013", "al. 2013 .", "2013 . recently", ". recently 3d", "recently 3d tomographic", "3d tomographic imaging", "tomographic imaging of", "imaging of isolation", "of isolation membranes", "isolation membranes has", "membranes has shown", "has shown the", "shown the cup", "the cup shaped", "cup shaped isolation", "shaped isolation membrane", "isolation membrane tightly", "membrane tightly sandwiched", "tightly sandwiched between", "sandwiched between two", "between two sheets", "two sheets of", "sheets of er", "of er and", "er and physically", "and physically connected", "physically connected to", "connected to the", "to the er", "the er through", "er through a", "through a narrow", "a narrow membrane", "narrow membrane tube", "tube hayashi", "hayashi nishino et", "nishino et al.", "et al. 2009", "2009 yla", "yla anttila et", "anttila et al.", "al. 2009 .", "2009 . this", ". this suggests", "this suggests that", "suggests that isolation", "that isolation membrane", "isolation membrane formation", "membrane formation and", "formation and elongation", "and elongation are", "elongation are guided", "are guided by", "guided by adjacent", "by adjacent er", "adjacent er sheets", "sheets supporting", "supporting the now", "the now prevalent", "now prevalent 'er", "prevalent 'er cradle'", "'er cradle' model", "model which", "which suggests that", "suggests that the", "that the isolation", "isolation membrane arises", "membrane arises from", "arises from the", "from the er", "er hayashi", "2009 shibutani", "shibutani & yoshimori", "& yoshimori 2014", "yoshimori 2014 .

autophagy", "2014 .

autophagy is", ".

autophagy is tightly", "is tightly regulated.", "tightly regulated. the", "regulated. the induction", "the induction of", "induction of autophagy", "of autophagy in", "autophagy in response", "in response to", "response to starvation", "to starvation is", "starvation is partly", "is partly mediated", "partly mediated by", "mediated by inactivation", "by inactivation of", "inactivation of the", "of the mammalian", "the mammalian target", "mammalian target of", "target of rapamycin", "rapamycin mtor", "noda & ohsumi", "& ohsumi 1998", "1998 and", "and activation of", "activation of jun", "of jun n", "jun n terminal", "n terminal kinase", "kinase jnk", "while energy loss", "energy loss induces", "loss induces autophagy", "induces autophagy by", "autophagy by activation", "by activation of", "activation of amp", "of amp kinase", "kinase ampk", "ampk . other", ". other pathways", "other pathways regulating", "pathways regulating autophagy", "regulating autophagy are", "autophagy are regulated", "are regulated by", "regulated by calcium", "calcium cyclic", "amp calpains", "calpains and the", "and the inositol", "the inositol trisphosphate", "trisphosphate ip3", "ip3 receptor", "receptor rubinsztein", "rubinsztein et al.", "et al. 2012", "al. 2012 .", "2012 .

in", ".

in mammals", "mammals two", "two complexes cooperatively", "complexes cooperatively produce", "cooperatively produce the", "produce the isolation", "the isolation membrane.", "isolation membrane. the", "membrane. the ulk", "the ulk complex", "ulk complex consists", "complex consists of", "consists of ulk1/2", "ulk1/2 atg13", "fip200 and", "atg101 alers", "alers et al.", "2012 . the", ". the pik3c3", "the pik3c3 containing", "pik3c3 containing beclin", "containing beclin 1", "beclin 1 complex", "1 complex consists", "consists of pik3c3", "pik3c3 vps34", "becn1 beclin", "1 atg6", "pik3r4 p150", "p150 vps15", "vps15 and", "atg14 barkor", "matsunaga et al.", "2009 zhong", "zhong et al.", "2009 . a", ". a similar", "a similar complex", "similar complex where", "complex where atg14", "where atg14 is", "atg14 is replaced", "is replaced by", "replaced by uvrag", "by uvrag functions", "uvrag functions later", "functions later in", "later in autophagosome", "in autophagosome maturation", "autophagosome maturation and", "maturation and endocytic", "and endocytic traffic", "traffic itakura", "itakura et al.", "2008 liang", "liang et al.", "2008 . binding", ". binding of", "binding of kiaa0226", "of kiaa0226 to", "kiaa0226 to this", "to this complex", "this complex negatively", "complex negatively regulates", "negatively regulates the", "regulates the maturation", "the maturation process", "process matsunaga", "2009 . the", ". the ulk", "the ulk and", "ulk and beclin", "and beclin 1", "beclin 1 complexes", "1 complexes are", "complexes are recruited", "are recruited to", "recruited to specific", "to specific autophagosome", "specific autophagosome nucleation", "autophagosome nucleation regions", "nucleation regions where", "regions where they", "where they stimulate", "they stimulate phosphatidylinositol", "stimulate phosphatidylinositol 3", "phosphatidylinositol 3 phosphate", "phosphate pi3p", "pi3p production", "production and facilitate", "and facilitate the", "facilitate the elongation", "the elongation and", "elongation and initial", "and initial membrane", "initial membrane curvature", "membrane curvature of", "curvature of the", "of the phagophore", "the phagophore membrane", "membrane carlsson", "carlsson & simonsen", "& simonsen 2015", "simonsen 2015 .

the", "2015 .

the ulk", ".

the ulk complex", "ulk complex is", "complex is considered", "is considered the", "considered the most", "the most upstream", "most upstream component", "upstream component of", "component of the", "the mammalian autophagy", "mammalian autophagy pathway", "pathway itakura", "itakura & mizushima", "& mizushima 2010", "acting as an", "as an integrator", "an integrator of", "integrator of the", "of the autophagy", "the autophagy signals", "autophagy signals downstream", "signals downstream of", "downstream of mtorc1.", "of mtorc1. it", "mtorc1. it is", "it is not", "is not fully", "not fully understood", "fully understood how", "understood how ulk1", "how ulk1 is", "ulk1 is modulated", "is modulated in", "modulated in response", "response to environmental", "to environmental cues.", "environmental cues. phosphorylation", "cues. phosphorylation plays", "phosphorylation plays an", "plays an essential", "an essential role", "role dunlop", "dunlop & tee", "& tee 2013", "2013 but", "but it is", "is not clear", "not clear how", "clear how phosphorylation", "how phosphorylation regulates", "phosphorylation regulates ulk1", "regulates ulk1 activities", "activities ravikumar", "al. 2010 .", "2010 . ulk1", ". ulk1 kinase", "ulk1 kinase activity", "kinase activity is", "activity is required", "is required for", "required for autophagy", "autophagy but", "but the substrate", "the substrate s", "s of", "of ulk1 that", "ulk1 that mediate", "that mediate its", "mediate its autophagic", "its autophagic function", "autophagic function are", "function are not", "are not certain.", "not certain. ulk1", "certain. ulk1 may", "ulk1 may also", "may also have", "also have kinase", "have kinase independent", "kinase independent functions", "independent functions in", "functions in autophagy", "autophagy wong", "wong et al.", "2013 .

", ".

pik3c3", "vps34 is", "is a class", "a class iii", "class iii phosphatidylinositol", "iii phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "3 kinase that", "kinase that produces", "that produces pi3p.", "produces pi3p. it", "pi3p. it is", "it is essential", "is essential for", "essential for the", "for the early", "the early stages", "early stages of", "stages of autophagy", "of autophagy and", "autophagy and colocalizes", "and colocalizes strongly", "colocalizes strongly with", "strongly with early", "with early autophagosome", "early autophagosome markers", "markers axe", "axe et al.", "2008 . becn1", ". becn1 binds", "becn1 binds several", "binds several further", "several further proteins", "further proteins that", "proteins that affect", "that affect autophagosome", "affect autophagosome formation.", "autophagosome formation. partners", "formation. partners that", "partners that induce", "that induce autophagy", "induce autophagy include", "autophagy include ambra1", "ambra1 fimia", "fimia et al.", "et al. 2007", "uvrag liang", "2006 and", "sh3glb1 takahashi", "takahashi et al.", "al. 2007 .", "2007 . binding", "binding of bcl2", "of bcl2 or", "bcl2 or bcl2l1", "bcl2l1 bcl", "xl inhibit", "autophagy pattingre", "pattingre et al.", "et al. 2005", "2005 ciechomska", "ciechomska et al.", ". the inositol", "the inositol 1", "inositol 1 4", "1 4 5", "4 5 trisphosphate", "5 trisphosphate receptor", "trisphosphate receptor complex", "receptor complex that", "complex that binds", "that binds bcl2", "binds bcl2 also", "bcl2 also interacts", "also interacts with", "interacts with becn1", "becn1 inhibiting", "autophagy vincencio", "vincencio et al.", "2009 . cisd2", "cisd2 nutrient", "nutrient deprivation autophagy", "deprivation autophagy factor", "autophagy factor 1", "1 naf1", "a component in", "component in the", "in the ip3r", "the ip3r complex", "complex interacts", "interacts with bcl2", "with bcl2 at", "bcl2 at the", "at the er", "the er and", "er and stabilizes", "and stabilizes the", "stabilizes the bcl2", "the bcl2 becn1", "bcl2 becn1 interaction", "interaction chang", "chang et al.", "2010 . starvation", ". starvation leads", "starvation leads to", "leads to activation", "to activation of", "activation of c", "of c jun", "c jun nh2", "jun nh2 terminal", "nh2 terminal kinase", "terminal kinase 1", "1 jnk1", "which results in", "results in the", "in the phosphorylation", "the phosphorylation of", "phosphorylation of bcl2", "of bcl2 and", "bcl2 and bcl2l1", "bcl2l1 which", "which release their", "release their binding", "their binding to", "binding to becn1", "to becn1 and", "becn1 and thus", "and thus induces", "thus induces autophagosome", "induces autophagosome formation", "formation wei", "wei et al.", "2008 .

ambra1", ".

ambra1 can", "

ambra1 can simultaneously", "can simultaneously bind", "simultaneously bind dynein", "bind dynein and", "dynein and the", "and the beclin", "the beclin 1", "beclin 1 complex.", "complex. during", "during nutrient starvation", "starvation ambra1", "ambra1 is phosphorylated", "is phosphorylated in", "phosphorylated in a", "in a ulk1", "a ulk1 dependent", "ulk1 dependent manner", "manner di", "di bartolomeo et", "bartolomeo et al.", "2010 . this", ". this phosphorylation", "this phosphorylation releases", "phosphorylation releases ambra1", "releases ambra1 associated", "ambra1 associated beclin", "associated beclin 1", "1 complexes from", "complexes from dynein", "from dynein and", "and the microtubule", "the microtubule network", "network freeing", "freeing the complex", "the complex to", "complex to translocate", "to translocate to", "translocate to autophagy", "to autophagy initiation", "autophagy initiation sites", "sites di", "2010 .

a", ".

a characteristic", "

a characteristic of", "characteristic of this", "of this early", "this early phase", "early phase of", "phase of autophagosome", "of autophagosome formation", "autophagosome formation is", "formation is the", "is the formation", "the formation of", "formation of pi3p", "of pi3p enriched", "pi3p enriched er", "enriched er associated", "er associated structures", "associated structures called", "structures called omegasomes", "omegasomes axe", "2008 or", "cradles hayashi", "2009 . omegasomes", ". omegasomes appear", "omegasomes appear to", "appear to concentrate", "to concentrate at", "concentrate at or", "at or near", "or near the", "near the connected", "the connected mitochondria", "connected mitochondria associated", "associated er membrane", "membrane hamasaki", "hamasaki et al.", "2013 . however", "however the", "the phagophore also", "phagophore also can", "also can incorporate", "can incorporate existing", "incorporate existing material", "existing material from", "material from other", "from other membrane", "other membrane sources", "membrane sources such", "sources such as", "such as er", "as er exit", "er exit sites", "sites eres", "the er golgi", "er golgi intermediate", "golgi intermediate compartment", "compartment ergic", "endosomes carlsson", "simonsen 2015 .", "2015 . omegasomes", ". omegasomes lead", "omegasomes lead to", "lead to the", "to the formation", "formation of the", "phagophore which", "which is thought", "is thought to", "thought to form", "to form de", "form de novo", "de novo by", "novo by an", "by an unknown", "an unknown mechanism", "mechanism simonsen", "simonsen & stenmark", "& stenmark 2008", "2008 roberts", "roberts & ktistakis", "& ktistakis 2013", "ktistakis 2013 .", "2013 . phagophore", ". phagophore expansion", "phagophore expansion is", "expansion is probably", "is probably mediated", "probably mediated by", "mediated by membrane", "by membrane uptake", "membrane uptake from", "uptake from endomembranes", "from endomembranes and", "endomembranes and semi", "and semi autonomous", "semi autonomous organelles", "organelles lamb", "2013 shibutani", "yoshimori 2014 .

atg9", "2014 .

atg9 is", ".

atg9 is a", "is a direct", "a direct target", "direct target of", "target of ulk1.", "of ulk1. in", "ulk1. in nutrient", "in nutrient rich", "nutrient rich conditions", "rich conditions mammalian", "conditions mammalian atg9", "mammalian atg9 is", "atg9 is localized", "is localized to", "localized to the", "to the trans", "the trans golgi", "trans golgi network", "golgi network and", "network and endosomes", "endosomes including", "early late", "late and recycling", "whereas under starvation", "under starvation conditions", "starvation conditions it", "conditions it is", "it is localized", "localized to autophagosomes", "autophagosomes in", "in a process", "a process that", "process that is", "that is dependent", "is dependent on", "dependent on ulk1", "ulk1 young", "young et al.", "al. 2006 .", "2006 . atg9", ". atg9 is", "atg9 is believed", "is believed to", "believed to play", "to play a", "play a role", "a role in", "role in the", "in the delivery", "the delivery of", "delivery of vesicles", "of vesicles derived", "vesicles derived from", "derived from existing", "from existing membranes", "existing membranes to", "membranes to the", "to the expanding", "the expanding phagophore", "phagophore lamb", "2013 . yeast", ". yeast atg9", "yeast atg9 forms", "atg9 forms a", "forms a complex", "a complex with", "complex with atg2", "with atg2 and", "atg2 and atg18", "atg18 reggiori", "reggiori et al.", "et al. 2004", "al. 2004 .", "2004 .

pi3p", ".

pi3p produced", "

pi3p produced at", "produced at the", "at the initiation", "the initiation site", "initiation site is", "site is sensed", "is sensed by", "sensed by wipi2b", "wipi2b the", "the mammalian homologue", "mammalian homologue of", "homologue of atg18", "atg18 polson", "polson et al.", "2010 . wipi2b", ". wipi2b then", "wipi2b then recruits", "then recruits atg16l1", "atg16l1 dooley", "dooley et al.", "et al. 2014", "al. 2014 .", "2014 . there", ". there are", "there are four", "are four wipi", "four wipi proteins", "wipi proteins in", "proteins in mammalian", "in mammalian cells", "cells proikas", "proikas cezanne et", "cezanne et al.", "et al. 2015", "al. 2015 .", "2015 . they", ". they are", "they are all", "are all likely", "all likely bind", "likely bind pi3p", "bind pi3p and", "pi3p and be", "and be recruited", "be recruited to", "recruited to membranes", "to membranes but", "membranes but the", "but the function", "function of wipi1", "wipi1 3", "3 and 4", "and 4 in", "4 in autophagy", "in autophagy is", "autophagy is not", "is not yet", "not yet clear.", "yet clear. wipi4", "wipi4 wdr45", "wdr45 has", "has been shown", "been shown to", "shown to bind", "to bind atg2", "bind atg2 and", "atg2 and to", "and to be", "to be involved", "be involved in", "involved in lipid", "in lipid droplet", "lipid droplet formation", "formation velikkakath", "velikkakath et al.", "mutations in wipi4", "in wipi4 have", "wipi4 have been", "have been shown", "shown to cause", "to cause a", "cause a neurodegenerative", "a neurodegenerative disease", "disease saitsu", "saitsu et al.", "al. 2013 .

the", "2013 .

the elongation", ".

the elongation of", "elongation of the", "the membrane that", "membrane that will", "that will become", "will become the", "become the autophagosome", "the autophagosome is", "autophagosome is regulated", "is regulated by", "regulated by two", "by two ubiquitination", "two ubiquitination like", "ubiquitination like reactions.", "like reactions. first", "first the", "the ubiquitin like", "ubiquitin like molecule", "like molecule atg12", "molecule atg12 is", "atg12 is conjugated", "is conjugated to", "conjugated to atg5", "to atg5 by", "atg5 by atg7", "atg7 which", "which acts as", "acts as an", "as an e1", "an e1 like", "e1 like activating", "like activating enzyme", "enzyme and", "atg10 which", "which has a", "has a role", "a role similar", "role similar to", "similar to an", "to an e2", "an e2 ubiquitin", "e2 ubiquitin conjugating", "ubiquitin conjugating enzyme.", "conjugating enzyme. the", "enzyme. the atg5:atg12", "the atg5:atg12 complex", "atg5:atg12 complex then", "complex then interacts", "then interacts non", "interacts non covalently", "non covalently with", "covalently with atg16l1.", "with atg16l1. this", "atg16l1. this complex", "this complex associates", "complex associates with", "associates with the", "with the forming", "the forming autophagosome", "forming autophagosome but", "autophagosome but dissociates", "but dissociates from", "dissociates from completed", "from completed autophagosomes", "autophagosomes geng", "geng & klionski", "& klionski 2008", "klionski 2008 .", "2008 . the", ". the second", "the second ubiquitin", "second ubiquitin like", "ubiquitin like reaction", "like reaction involves", "reaction involves the", "involves the conjugation", "the conjugation of", "conjugation of ubiquitin", "of ubiquitin like", "ubiquitin like molecules", "like molecules of", "molecules of the", "of the lc3", "the lc3 family", "family weidberg", "weidberg et al.", "2010 . lc3", ". lc3 proteins", "lc3 proteins are", "proteins are conjugated", "are conjugated through", "conjugated through their", "through their c", "their c terminal", "c terminal glycine", "terminal glycine residues", "glycine residues with", "residues with pe", "with pe by", "pe by the", "by the e1", "the e1 like", "e1 like atg7", "like atg7 and", "atg7 and e2", "and e2 like", "e2 like atg3.", "like atg3. this", "atg3. this allows", "this allows lc3", "allows lc3 proteins", "lc3 proteins to", "proteins to associate", "to associate with", "associate with the", "with the autophagosome", "the autophagosome membrane.", "autophagosome membrane.

the", "membrane.

the atg12:atg5:atg16l1", "

the atg12:atg5:atg16l1 complex", "complex mizushima", "2011 acts", "as an e3", "an e3 like", "e3 like enzyme", "like enzyme for", "enzyme for the", "for the conjugation", "conjugation of lc3", "of lc3 family", "lc3 family proteins", "proteins mammalian", "mammalian homologues of", "homologues of yeast", "of yeast atg8", "atg8 to", "phosphatidylethanolamine pe", "hanada et al.", "2007 fujita", "fujita et al.", "2008 . lc3", ". lc3 pe", "lc3 pe can", "pe can be", "can be deconjugated", "be deconjugated by", "deconjugated by the", "by the protease", "the protease atg4", "atg4 li", "li et al.", "2011 2012", "2012 . atg4", ". atg4 is", "atg4 is also", "is also responsible", "also responsible for", "responsible for priming", "for priming lc3", "priming lc3 proteins", "lc3 proteins by", "proteins by cleaving", "by cleaving the", "cleaving the c", "the c terminus", "c terminus to", "terminus to expose", "to expose a", "expose a glycine", "a glycine residue", "residue kirisako", "kirisako et al", "al 2000", "2000 scherz", "scherz shouval et", "shouval et al.", "2007 . lc3", "lc3 proteins remain", "proteins remain associated", "remain associated with", "associated with autophagosomes", "with autophagosomes until", "autophagosomes until they", "until they fuse", "they fuse with", "fuse with lysosomes.", "with lysosomes. the", "lysosomes. the lc3", "the lc3 like", "lc3 like proteins", "like proteins inside", "proteins inside the", "inside the resulting", "the resulting autolysosomes", "resulting autolysosomes are", "autolysosomes are degraded", "degraded while", "while those on", "those on the", "on the cytoplasmic", "the cytoplasmic surface", "cytoplasmic surface are", "surface are delipidated", "are delipidated and", "delipidated and recycled.", "and recycled. atg5:atg12:atg16l1", "recycled. atg5:atg12:atg16l1 positive", "atg5:atg12:atg16l1 positive lc3", "positive lc3 negative", "lc3 negative vesicles", "negative vesicles represent", "vesicles represent pre", "represent pre autophagosomal", "pre autophagosomal structures", "structures pre", "pre phagophores and", "phagophores and possibly", "and possibly early", "possibly early phagophores", "positive lc3 positive", "lc3 positive structures", "positive structures can", "structures can be", "can be considered", "be considered to", "considered to be", "to be phagophores", "and atg5:atg12:atg16l1 negative", "atg5:atg12:atg16l1 negative lc3", "negative lc3 positive", "lc3 positive vesicles", "positive vesicles can", "vesicles can be", "can be regarded", "be regarded as", "regarded as mature", "as mature autophagosomes", "autophagosomes tandia", "tandia et al.", "al. 2011 .

phagophore", "2011 .

phagophore expansion", ".

phagophore expansion is", "from endomembranes as", "endomembranes as well", "as well as", "well as from", "as from semiautonomous", "from semiautonomous organelles", "yoshimori 2014 .

the", "2014 .

the mechanisms", ".

the mechanisms involved", "mechanisms involved in", "involved in the", "in the closure", "the closure of", "closure of the", "phagophore membrane are", "membrane are poorly", "are poorly understood.", "poorly understood. as", "understood. as the", "as the phagophore", "the phagophore is", "phagophore is a", "is a double", "a double membraned", "double membraned structure", "structure its", "its closure involves", "closure involves the", "involves the fusion", "the fusion of", "fusion of a", "of a narrow", "a narrow opening", "opening a", "that is distinct", "is distinct from", "distinct from other", "other membrane fusion", "membrane fusion events", "events carlsson", "2015 . the", ". the topology", "the topology of", "topology of the", "phagophore is similar", "is similar to", "similar to that", "to that of", "that of cytokinesis", "cytokinesis viral", "viral budding or", "budding or multivesicular", "or multivesicular body", "body mvb", "mvb formation.", "formation. these processes", "these processes rely", "processes rely on", "rely on the", "on the endosomal", "the endosomal sorting", "endosomal sorting complex", "sorting complex required", "complex required for", "required for transport", "transport escrt", "rusten et al.", "2012 . escrt", ". escrt and", "escrt and associated", "and associated proteins", "associated proteins facilitate", "proteins facilitate membrane", "facilitate membrane budding", "membrane budding away", "budding away from", "away from the", "from the cytosol", "the cytosol and", "cytosol and subsequent", "and subsequent cleavage", "subsequent cleavage of", "cleavage of the", "of the bud", "the bud neck", "neck hurley", "hurley & hanson", "& hanson 2010", "hanson 2010 .", "2010 . several", ". several studies", "several studies have", "studies have shown", "have shown that", "shown that depletion", "that depletion of", "depletion of escrt", "of escrt subunits", "escrt subunits or", "subunits or the", "or the regulatory", "the regulatory atpase", "regulatory atpase vps4", "atpase vps4 causes", "vps4 causes an", "causes an accumulation", "an accumulation of", "accumulation of autophagosomes", "autophagosomes filimonenko", "filimonenko et al.", "2007 rusten", "2007 but", "not clear whether", "clear whether escrts", "whether escrts are", "escrts are required", "are required for", "required for autophagosome", "for autophagosome closure", "autophagosome closure or", "closure or for", "or for autophagosome", "for autophagosome to", "autophagosome to endosome", "to endosome fusion.", "endosome fusion. uvrag", "fusion. uvrag is", "uvrag is also", "is also involved", "also involved in", "in the maturation", "the maturation step", "step recruiting", "recruiting proteins that", "proteins that bring", "that bring about", "bring about membrane", "about membrane fusion", "membrane fusion such", "fusion such as", "such as the", "as the class", "the class c", "class c vps", "c vps proteins", "proteins which", "which activate rab7", "activate rab7 thereby", "rab7 thereby promoting", "thereby promoting fusion", "promoting fusion with", "fusion with late", "with late endosomes", "late endosomes and", "endosomes and lysosomes", "lysosomes liang", "macroautophagy hereafter referred", "hereafter referred to as", "referred to as autophagy", "as autophagy acts", "autophagy acts as", "acts as a buffer", "as a buffer against", "a buffer against starvation", "buffer against starvation by", "against starvation by liberating", "starvation by liberating building", "by liberating building materials", "liberating building materials and", "building materials and energy", "materials and energy sources", "and energy sources from", "energy sources from cellular", "sources from cellular components.", "from cellular components. it", "cellular components. it has", "components. it has additional", "it has additional roles", "has additional roles in", "additional roles in embryonic", "roles in embryonic development", "embryonic development removal", "development removal of", "removal of apoptotic cells", "of apoptotic cells or", "apoptotic cells or organelles", "or organelles antigen", "organelles antigen presentation", "antigen presentation protection", "presentation protection against", "protection against toxins and", "against toxins and as", "toxins and as a", "and as a degradation", "as a degradation route", "a degradation route for", "degradation route for aggregate", "route for aggregate prone", "for aggregate prone proteins", "aggregate prone proteins and", "prone proteins and infectious", "proteins and infectious agents.", "and infectious agents. the", "infectious agents. the dysregulation", "agents. the dysregulation of", "the dysregulation of autophagy", "dysregulation of autophagy is", "of autophagy is involved", "autophagy is involved in", "is involved in several", "involved in several human", "in several human diseases", "human diseases for", "diseases for example", "for example crohn's", "example crohn's disease", "crohn's disease cancer", "disease cancer and", "and neurodegeneration ravikumar", "neurodegeneration ravikumar et", "ravikumar et al. 2010", "et al. 2010 .
autophagy", "al. 2010 .
autophagy is", "2010 .
autophagy is highly", ".
autophagy is highly conserved", "is highly conserved from", "highly conserved from yeast", "conserved from yeast to", "from yeast to humans", "to humans much", "humans much of", "much of the machinery", "of the machinery was", "the machinery was first", "machinery was first identified", "was first identified in", "first identified in yeast", "in yeast see", "yeast see klionsky", "see klionsky et al.", "klionsky et al. 2011", "et al. 2011 .", "al. 2011 . initially", ". initially double", "initially double membraned", "double membraned cup shaped", "membraned cup shaped structures", "cup shaped structures called", "shaped structures called the", "structures called the isolation", "called the isolation membrane", "the isolation membrane or", "isolation membrane or phagophore", "membrane or phagophore engulf", "or phagophore engulf portions", "phagophore engulf portions of", "engulf portions of cytoplasm.", "portions of cytoplasm. the", "of cytoplasm. the membranes", "cytoplasm. the membranes fuse", "the membranes fuse to", "membranes fuse to form", "fuse to form the", "to form the autophagosome.", "form the autophagosome. in", "the autophagosome. in yeast", "autophagosome. in yeast cells", "yeast cells autophagosomes", "cells autophagosomes are", "autophagosomes are formed at", "are formed at the", "formed at the phagophore", "at the phagophore assembly", "the phagophore assembly site", "assembly site pas", "pas next to", "next to the vacuole.", "to the vacuole. in", "the vacuole. in mammals", "in mammals autophagosomes", "mammals autophagosomes appear", "autophagosomes appear throughout the", "appear throughout the cytoplasm", "throughout the cytoplasm then", "the cytoplasm then move", "cytoplasm then move along", "then move along microtubules", "move along microtubules towards", "along microtubules towards the", "microtubules towards the microtubule", "towards the microtubule organising", "the microtubule organising centre.", "microtubule organising centre. this", "organising centre. this transport", "centre. this transport requires", "this transport requires microtubules", "transport requires microtubules and", "requires microtubules and the", "microtubules and the function", "and the function of", "the function of dynein", "function of dynein motor", "of dynein motor proteins", "motor proteins depolymerization", "proteins depolymerization of", "depolymerization of microtubules or", "of microtubules or inhibition", "microtubules or inhibition of", "or inhibition of dynein", "inhibition of dynein dependent", "of dynein dependent transport", "dynein dependent transport results", "dependent transport results in", "transport results in inhibition", "results in inhibition of", "in inhibition of autophagy", "of autophagy kochl", "autophagy kochl et", "kochl et al. 2006", "al. 2006 kimura", "2006 kimura et", "kimura et al. 2008", "et al. 2008 .", "al. 2008 . autophagosomes", "2008 . autophagosomes fuse", ". autophagosomes fuse with", "autophagosomes fuse with lysosomes", "fuse with lysosomes forming", "with lysosomes forming autolysosomes", "lysosomes forming autolysosomes whose", "forming autolysosomes whose contents", "autolysosomes whose contents are", "whose contents are degraded", "contents are degraded by", "are degraded by lysosomal", "degraded by lysosomal hydrolases", "lysosomal hydrolases mizushima", "hydrolases mizushima et", "mizushima et al. 2011", "et al. 2011 .

the", "al. 2011 .

the origins", "2011 .

the origins of", ".

the origins of the", "origins of the autophagosomal", "of the autophagosomal membrane", "the autophagosomal membrane and", "autophagosomal membrane and the", "and the incorporation", "the incorporation of", "incorporation of existing membrane", "of existing membrane material", "existing membrane material have", "membrane material have been", "material have been extensively", "have been extensively debated.", "been extensively debated. the", "extensively debated. the endoplasmic", "debated. the endoplasmic reticulum", "endoplasmic reticulum er", "er mitochondria", "mitochondria mitochondria associated", "mitochondria associated er membranes", "er membranes mams", "mams the", "the golgi the", "golgi the plasma", "the plasma membrane and", "plasma membrane and recycling", "membrane and recycling endosomes", "and recycling endosomes have", "recycling endosomes have all", "endosomes have all been", "have all been implicated", "all been implicated in", "been implicated in the", "implicated in the nucleation", "in the nucleation of", "the nucleation of the", "nucleation of the isolation", "of the isolation membrane", "the isolation membrane and", "isolation membrane and subsequent", "membrane and subsequent growth", "and subsequent growth of", "subsequent growth of the", "growth of the membrane", "the membrane lamb", "membrane lamb et", "lamb et al. 2013", "et al. 2013 .", "al. 2013 . recently", "2013 . recently 3d", ". recently 3d tomographic", "recently 3d tomographic imaging", "3d tomographic imaging of", "tomographic imaging of isolation", "imaging of isolation membranes", "of isolation membranes has", "isolation membranes has shown", "membranes has shown the", "has shown the cup", "shown the cup shaped", "the cup shaped isolation", "cup shaped isolation membrane", "shaped isolation membrane tightly", "isolation membrane tightly sandwiched", "membrane tightly sandwiched between", "tightly sandwiched between two", "sandwiched between two sheets", "between two sheets of", "two sheets of er", "sheets of er and", "of er and physically", "er and physically connected", "and physically connected to", "physically connected to the", "connected to the er", "to the er through", "the er through a", "er through a narrow", "through a narrow membrane", "a narrow membrane tube", "membrane tube hayashi", "tube hayashi nishino", "hayashi nishino et al.", "nishino et al. 2009", "al. 2009 yla", "2009 yla anttila", "yla anttila et al.", "anttila et al. 2009", "et al. 2009 .", "al. 2009 . this", "2009 . this suggests", ". this suggests that", "this suggests that isolation", "suggests that isolation membrane", "that isolation membrane formation", "isolation membrane formation and", "membrane formation and elongation", "formation and elongation are", "and elongation are guided", "elongation are guided by", "are guided by adjacent", "guided by adjacent er", "by adjacent er sheets", "er sheets supporting", "sheets supporting the", "supporting the now prevalent", "the now prevalent 'er", "now prevalent 'er cradle'", "prevalent 'er cradle' model", "cradle' model which", "model which suggests", "which suggests that the", "suggests that the isolation", "that the isolation membrane", "the isolation membrane arises", "isolation membrane arises from", "membrane arises from the", "arises from the er", "the er hayashi", "er hayashi nishino", "al. 2009 shibutani", "2009 shibutani &", "shibutani & yoshimori 2014", "& yoshimori 2014 .

autophagy", "yoshimori 2014 .

autophagy is", "2014 .

autophagy is tightly", ".

autophagy is tightly regulated.", "is tightly regulated. the", "tightly regulated. the induction", "regulated. the induction of", "the induction of autophagy", "induction of autophagy in", "of autophagy in response", "autophagy in response to", "in response to starvation", "response to starvation is", "to starvation is partly", "starvation is partly mediated", "is partly mediated by", "partly mediated by inactivation", "mediated by inactivation of", "by inactivation of the", "inactivation of the mammalian", "of the mammalian target", "the mammalian target of", "mammalian target of rapamycin", "of rapamycin mtor", "mtor noda", "noda & ohsumi 1998", "ohsumi 1998 and", "1998 and activation", "and activation of jun", "activation of jun n", "of jun n terminal", "jun n terminal kinase", "terminal kinase jnk", "jnk while", "while energy loss induces", "energy loss induces autophagy", "loss induces autophagy by", "induces autophagy by activation", "autophagy by activation of", "by activation of amp", "activation of amp kinase", "amp kinase ampk", "kinase ampk .", "ampk . other pathways", ". other pathways regulating", "other pathways regulating autophagy", "pathways regulating autophagy are", "regulating autophagy are regulated", "autophagy are regulated by", "are regulated by calcium", "by calcium cyclic", "calcium cyclic amp", "cyclic amp calpains", "amp calpains and", "calpains and the inositol", "and the inositol trisphosphate", "inositol trisphosphate ip3", "receptor rubinsztein et", "rubinsztein et al. 2012", "et al. 2012 .", "al. 2012 .

in", "2012 .

in mammals", "

in mammals two", "mammals two complexes", "two complexes cooperatively produce", "complexes cooperatively produce the", "cooperatively produce the isolation", "produce the isolation membrane.", "the isolation membrane. the", "isolation membrane. the ulk", "membrane. the ulk complex", "the ulk complex consists", "ulk complex consists of", "complex consists of ulk1/2", "of ulk1/2 atg13", "atg13 fip200", "fip200 and atg101", "and atg101 alers", "atg101 alers et", "alers et al. 2012", "al. 2012 . the", "2012 . the pik3c3", ". the pik3c3 containing", "the pik3c3 containing beclin", "pik3c3 containing beclin 1", "containing beclin 1 complex", "beclin 1 complex consists", "1 complex consists of", "complex consists of pik3c3", "of pik3c3 vps34", "vps34 becn1", "becn1 beclin 1", "beclin 1 atg6", "atg6 pik3r4", "vps15 and atg14", "and atg14 barkor", "barkor matsunaga", "matsunaga et al. 2009", "al. 2009 zhong", "2009 zhong et", "zhong et al. 2009", "al. 2009 . a", "2009 . a similar", ". a similar complex", "a similar complex where", "similar complex where atg14", "complex where atg14 is", "where atg14 is replaced", "atg14 is replaced by", "is replaced by uvrag", "replaced by uvrag functions", "by uvrag functions later", "uvrag functions later in", "functions later in autophagosome", "later in autophagosome maturation", "in autophagosome maturation and", "autophagosome maturation and endocytic", "maturation and endocytic traffic", "endocytic traffic itakura", "traffic itakura et", "itakura et al. 2008", "al. 2008 liang", "2008 liang et", "liang et al. 2008", "al. 2008 . binding", "2008 . binding of", ". binding of kiaa0226", "binding of kiaa0226 to", "of kiaa0226 to this", "kiaa0226 to this complex", "to this complex negatively", "this complex negatively regulates", "complex negatively regulates the", "negatively regulates the maturation", "regulates the maturation process", "maturation process matsunaga", "process matsunaga et", "al. 2009 . the", "2009 . the ulk", ". the ulk and", "the ulk and beclin", "ulk and beclin 1", "and beclin 1 complexes", "beclin 1 complexes are", "1 complexes are recruited", "complexes are recruited to", "are recruited to specific", "recruited to specific autophagosome", "to specific autophagosome nucleation", "specific autophagosome nucleation regions", "autophagosome nucleation regions where", "nucleation regions where they", "regions where they stimulate", "where they stimulate phosphatidylinositol", "they stimulate phosphatidylinositol 3", "stimulate phosphatidylinositol 3 phosphate", "3 phosphate pi3p", "pi3p production and", "production and facilitate the", "and facilitate the elongation", "facilitate the elongation and", "the elongation and initial", "elongation and initial membrane", "and initial membrane curvature", "initial membrane curvature of", "membrane curvature of the", "curvature of the phagophore", "of the phagophore membrane", "phagophore membrane carlsson", "membrane carlsson &", "carlsson & simonsen 2015", "& simonsen 2015 .

the", "simonsen 2015 .

the ulk", "2015 .

the ulk complex", ".

the ulk complex is", "ulk complex is considered", "complex is considered the", "is considered the most", "considered the most upstream", "the most upstream component", "most upstream component of", "upstream component of the", "component of the mammalian", "of the mammalian autophagy", "the mammalian autophagy pathway", "autophagy pathway itakura", "pathway itakura &", "itakura & mizushima 2010", "2010 acting", "acting as an integrator", "as an integrator of", "an integrator of the", "integrator of the autophagy", "of the autophagy signals", "the autophagy signals downstream", "autophagy signals downstream of", "signals downstream of mtorc1.", "downstream of mtorc1. it", "of mtorc1. it is", "mtorc1. it is not", "it is not fully", "is not fully understood", "not fully understood how", "fully understood how ulk1", "understood how ulk1 is", "how ulk1 is modulated", "ulk1 is modulated in", "is modulated in response", "modulated in response to", "in response to environmental", "response to environmental cues.", "to environmental cues. phosphorylation", "environmental cues. phosphorylation plays", "cues. phosphorylation plays an", "phosphorylation plays an essential", "plays an essential role", "essential role dunlop", "role dunlop &", "dunlop & tee 2013", "tee 2013 but", "2013 but it", "but it is not", "it is not clear", "is not clear how", "not clear how phosphorylation", "clear how phosphorylation regulates", "how phosphorylation regulates ulk1", "phosphorylation regulates ulk1 activities", "ulk1 activities ravikumar", "activities ravikumar et", "et al. 2010 .", "al. 2010 . ulk1", "2010 . ulk1 kinase", ". ulk1 kinase activity", "ulk1 kinase activity is", "kinase activity is required", "activity is required for", "is required for autophagy", "for autophagy but", "autophagy but the", "but the substrate s", "substrate s of", "s of ulk1", "of ulk1 that mediate", "ulk1 that mediate its", "that mediate its autophagic", "mediate its autophagic function", "its autophagic function are", "autophagic function are not", "function are not certain.", "are not certain. ulk1", "not certain. ulk1 may", "certain. ulk1 may also", "ulk1 may also have", "may also have kinase", "also have kinase independent", "have kinase independent functions", "kinase independent functions in", "independent functions in autophagy", "in autophagy wong", "autophagy wong et", "wong et al. 2013", "al. 2013 .

", "2013 .

pik3c3", "

pik3c3 vps34", "vps34 is a", "is a class iii", "a class iii phosphatidylinositol", "class iii phosphatidylinositol 3", "iii phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase that", "3 kinase that produces", "kinase that produces pi3p.", "that produces pi3p. it", "produces pi3p. it is", "pi3p. it is essential", "it is essential for", "is essential for the", "essential for the early", "for the early stages", "the early stages of", "early stages of autophagy", "stages of autophagy and", "of autophagy and colocalizes", "autophagy and colocalizes strongly", "and colocalizes strongly with", "colocalizes strongly with early", "strongly with early autophagosome", "with early autophagosome markers", "autophagosome markers axe", "markers axe et", "axe et al. 2008", "al. 2008 . becn1", "2008 . becn1 binds", ". becn1 binds several", "becn1 binds several further", "binds several further proteins", "several further proteins that", "further proteins that affect", "proteins that affect autophagosome", "that affect autophagosome formation.", "affect autophagosome formation. partners", "autophagosome formation. partners that", "formation. partners that induce", "partners that induce autophagy", "that induce autophagy include", "induce autophagy include ambra1", "include ambra1 fimia", "ambra1 fimia et", "fimia et al. 2007", "2007 uvrag", "uvrag liang et", "liang et al. 2006", "al. 2006 and", "2006 and sh3glb1", "and sh3glb1 takahashi", "sh3glb1 takahashi et", "takahashi et al. 2007", "et al. 2007 .", "al. 2007 . binding", "2007 . binding of", ". binding of bcl2", "binding of bcl2 or", "of bcl2 or bcl2l1", "or bcl2l1 bcl", "bcl2l1 bcl xl", "bcl xl inhibit", "xl inhibit autophagy", "inhibit autophagy pattingre", "autophagy pattingre et", "pattingre et al. 2005", "al. 2005 ciechomska", "2005 ciechomska et", "ciechomska et al. 2009", "2009 . the inositol", ". the inositol 1", "the inositol 1 4", "inositol 1 4 5", "1 4 5 trisphosphate", "4 5 trisphosphate receptor", "5 trisphosphate receptor complex", "trisphosphate receptor complex that", "receptor complex that binds", "complex that binds bcl2", "that binds bcl2 also", "binds bcl2 also interacts", "bcl2 also interacts with", "also interacts with becn1", "with becn1 inhibiting", "becn1 inhibiting autophagy", "inhibiting autophagy vincencio", "autophagy vincencio et", "vincencio et al. 2009", "al. 2009 . cisd2", ". cisd2 nutrient", "cisd2 nutrient deprivation", "nutrient deprivation autophagy factor", "deprivation autophagy factor 1", "factor 1 naf1", "naf1 a", "a component in the", "component in the ip3r", "in the ip3r complex", "ip3r complex interacts", "complex interacts with", "interacts with bcl2 at", "with bcl2 at the", "bcl2 at the er", "at the er and", "the er and stabilizes", "er and stabilizes the", "and stabilizes the bcl2", "stabilizes the bcl2 becn1", "the bcl2 becn1 interaction", "becn1 interaction chang", "interaction chang et", "chang et al. 2010", "al. 2010 . starvation", "2010 . starvation leads", ". starvation leads to", "starvation leads to activation", "leads to activation of", "to activation of c", "activation of c jun", "of c jun nh2", "c jun nh2 terminal", "jun nh2 terminal kinase", "nh2 terminal kinase 1", "kinase 1 jnk1", "jnk1 which", "which results in the", "results in the phosphorylation", "in the phosphorylation of", "the phosphorylation of bcl2", "phosphorylation of bcl2 and", "of bcl2 and bcl2l1", "and bcl2l1 which", "bcl2l1 which release", "which release their binding", "release their binding to", "their binding to becn1", "binding to becn1 and", "to becn1 and thus", "becn1 and thus induces", "and thus induces autophagosome", "thus induces autophagosome formation", "autophagosome formation wei", "formation wei et", "wei et al. 2008", "al. 2008 .

ambra1", "2008 .

ambra1 can", ".

ambra1 can simultaneously", "

ambra1 can simultaneously bind", "can simultaneously bind dynein", "simultaneously bind dynein and", "bind dynein and the", "dynein and the beclin", "and the beclin 1", "the beclin 1 complex.", "1 complex. during", "complex. during nutrient", "nutrient starvation ambra1", "starvation ambra1 is", "ambra1 is phosphorylated in", "is phosphorylated in a", "phosphorylated in a ulk1", "in a ulk1 dependent", "a ulk1 dependent manner", "dependent manner di", "manner di bartolomeo", "di bartolomeo et al.", "bartolomeo et al. 2010", "al. 2010 . this", "2010 . this phosphorylation", ". this phosphorylation releases", "this phosphorylation releases ambra1", "phosphorylation releases ambra1 associated", "releases ambra1 associated beclin", "ambra1 associated beclin 1", "associated beclin 1 complexes", "beclin 1 complexes from", "1 complexes from dynein", "complexes from dynein and", "from dynein and the", "dynein and the microtubule", "and the microtubule network", "microtubule network freeing", "network freeing the", "freeing the complex to", "the complex to translocate", "complex to translocate to", "to translocate to autophagy", "translocate to autophagy initiation", "to autophagy initiation sites", "initiation sites di", "sites di bartolomeo", "al. 2010 .

a", "2010 .

a characteristic", ".

a characteristic of", "

a characteristic of this", "characteristic of this early", "of this early phase", "this early phase of", "early phase of autophagosome", "phase of autophagosome formation", "of autophagosome formation is", "autophagosome formation is the", "formation is the formation", "is the formation of", "the formation of pi3p", "formation of pi3p enriched", "of pi3p enriched er", "pi3p enriched er associated", "enriched er associated structures", "er associated structures called", "associated structures called omegasomes", "called omegasomes axe", "omegasomes axe et", "al. 2008 or", "2008 or cradles", "or cradles hayashi", "cradles hayashi nishino", "al. 2009 . omegasomes", "2009 . omegasomes appear", ". omegasomes appear to", "omegasomes appear to concentrate", "appear to concentrate at", "to concentrate at or", "concentrate at or near", "at or near the", "or near the connected", "near the connected mitochondria", "the connected mitochondria associated", "connected mitochondria associated er", "mitochondria associated er membrane", "er membrane hamasaki", "membrane hamasaki et", "hamasaki et al. 2013", "al. 2013 . however", ". however the", "however the phagophore", "the phagophore also can", "phagophore also can incorporate", "also can incorporate existing", "can incorporate existing material", "incorporate existing material from", "existing material from other", "material from other membrane", "from other membrane sources", "other membrane sources such", "membrane sources such as", "sources such as er", "such as er exit", "as er exit sites", "exit sites eres", "eres the", "the er golgi intermediate", "er golgi intermediate compartment", "intermediate compartment ergic", "ergic the", "recycling endosomes carlsson", "endosomes carlsson &", "& simonsen 2015 .", "simonsen 2015 . omegasomes", "2015 . omegasomes lead", ". omegasomes lead to", "omegasomes lead to the", "lead to the formation", "to the formation of", "the formation of the", "formation of the isolation", "or phagophore which", "phagophore which is", "which is thought to", "is thought to form", "thought to form de", "to form de novo", "form de novo by", "de novo by an", "novo by an unknown", "by an unknown mechanism", "unknown mechanism simonsen", "mechanism simonsen &", "simonsen & stenmark 2008", "stenmark 2008 roberts", "2008 roberts &", "roberts & ktistakis 2013", "& ktistakis 2013 .", "ktistakis 2013 . phagophore", "2013 . phagophore expansion", ". phagophore expansion is", "phagophore expansion is probably", "expansion is probably mediated", "is probably mediated by", "probably mediated by membrane", "mediated by membrane uptake", "by membrane uptake from", "membrane uptake from endomembranes", "uptake from endomembranes and", "from endomembranes and semi", "endomembranes and semi autonomous", "and semi autonomous organelles", "autonomous organelles lamb", "organelles lamb et", "al. 2013 shibutani", "2013 shibutani &", "& yoshimori 2014 .

atg9", "yoshimori 2014 .

atg9 is", "2014 .

atg9 is a", ".

atg9 is a direct", "is a direct target", "a direct target of", "direct target of ulk1.", "target of ulk1. in", "of ulk1. in nutrient", "ulk1. in nutrient rich", "in nutrient rich conditions", "nutrient rich conditions mammalian", "rich conditions mammalian atg9", "conditions mammalian atg9 is", "mammalian atg9 is localized", "atg9 is localized to", "is localized to the", "localized to the trans", "to the trans golgi", "the trans golgi network", "trans golgi network and", "golgi network and endosomes", "and endosomes including", "endosomes including early", "including early late", "early late and", "late and recycling endosomes", "endosomes whereas", "whereas under starvation conditions", "under starvation conditions it", "starvation conditions it is", "conditions it is localized", "it is localized to", "is localized to autophagosomes", "to autophagosomes in", "autophagosomes in a", "in a process that", "a process that is", "process that is dependent", "that is dependent on", "is dependent on ulk1", "on ulk1 young", "ulk1 young et", "young et al. 2006", "et al. 2006 .", "al. 2006 . atg9", "2006 . atg9 is", ". atg9 is believed", "atg9 is believed to", "is believed to play", "believed to play a", "to play a role", "play a role in", "a role in the", "role in the delivery", "in the delivery of", "the delivery of vesicles", "delivery of vesicles derived", "of vesicles derived from", "vesicles derived from existing", "derived from existing membranes", "from existing membranes to", "existing membranes to the", "membranes to the expanding", "to the expanding phagophore", "expanding phagophore lamb", "phagophore lamb et", "al. 2013 . yeast", "2013 . yeast atg9", ". yeast atg9 forms", "yeast atg9 forms a", "atg9 forms a complex", "forms a complex with", "a complex with atg2", "complex with atg2 and", "with atg2 and atg18", "and atg18 reggiori", "atg18 reggiori et", "reggiori et al. 2004", "et al. 2004 .", "al. 2004 .

pi3p", "2004 .

pi3p produced", ".

pi3p produced at", "

pi3p produced at the", "produced at the initiation", "at the initiation site", "the initiation site is", "initiation site is sensed", "site is sensed by", "is sensed by wipi2b", "by wipi2b the", "wipi2b the mammalian", "the mammalian homologue of", "mammalian homologue of atg18", "of atg18 polson", "atg18 polson et", "polson et al. 2010", "al. 2010 . wipi2b", "2010 . wipi2b then", ". wipi2b then recruits", "wipi2b then recruits atg16l1", "recruits atg16l1 dooley", "atg16l1 dooley et", "dooley et al. 2014", "et al. 2014 .", "al. 2014 . there", "2014 . there are", ". there are four", "there are four wipi", "are four wipi proteins", "four wipi proteins in", "wipi proteins in mammalian", "proteins in mammalian cells", "mammalian cells proikas", "cells proikas cezanne", "proikas cezanne et al.", "cezanne et al. 2015", "et al. 2015 .", "al. 2015 . they", "2015 . they are", ". they are all", "they are all likely", "are all likely bind", "all likely bind pi3p", "likely bind pi3p and", "bind pi3p and be", "pi3p and be recruited", "and be recruited to", "be recruited to membranes", "recruited to membranes but", "to membranes but the", "membranes but the function", "but the function of", "the function of wipi1", "of wipi1 3", "wipi1 3 and", "3 and 4 in", "and 4 in autophagy", "4 in autophagy is", "in autophagy is not", "autophagy is not yet", "is not yet clear.", "not yet clear. wipi4", "clear. wipi4 wdr45", "wdr45 has been", "has been shown to", "been shown to bind", "shown to bind atg2", "to bind atg2 and", "bind atg2 and to", "atg2 and to be", "and to be involved", "to be involved in", "be involved in lipid", "involved in lipid droplet", "in lipid droplet formation", "droplet formation velikkakath", "formation velikkakath et", "velikkakath et al. 2012", "2012 mutations", "mutations in wipi4 have", "in wipi4 have been", "wipi4 have been shown", "have been shown to", "been shown to cause", "shown to cause a", "to cause a neurodegenerative", "cause a neurodegenerative disease", "neurodegenerative disease saitsu", "disease saitsu et", "saitsu et al. 2013", "et al. 2013 .

the", "al. 2013 .

the elongation", "2013 .

the elongation of", ".

the elongation of the", "elongation of the membrane", "of the membrane that", "the membrane that will", "membrane that will become", "that will become the", "will become the autophagosome", "become the autophagosome is", "the autophagosome is regulated", "autophagosome is regulated by", "is regulated by two", "regulated by two ubiquitination", "by two ubiquitination like", "two ubiquitination like reactions.", "ubiquitination like reactions. first", "reactions. first the", "first the ubiquitin", "the ubiquitin like molecule", "ubiquitin like molecule atg12", "like molecule atg12 is", "molecule atg12 is conjugated", "atg12 is conjugated to", "is conjugated to atg5", "conjugated to atg5 by", "to atg5 by atg7", "by atg7 which", "atg7 which acts", "which acts as an", "acts as an e1", "as an e1 like", "an e1 like activating", "e1 like activating enzyme", "activating enzyme and", "enzyme and atg10", "and atg10 which", "atg10 which has", "which has a role", "has a role similar", "a role similar to", "role similar to an", "similar to an e2", "to an e2 ubiquitin", "an e2 ubiquitin conjugating", "e2 ubiquitin conjugating enzyme.", "ubiquitin conjugating enzyme. the", "conjugating enzyme. the atg5:atg12", "enzyme. the atg5:atg12 complex", "the atg5:atg12 complex then", "atg5:atg12 complex then interacts", "complex then interacts non", "then interacts non covalently", "interacts non covalently with", "non covalently with atg16l1.", "covalently with atg16l1. this", "with atg16l1. this complex", "atg16l1. this complex associates", "this complex associates with", "complex associates with the", "associates with the forming", "with the forming autophagosome", "the forming autophagosome but", "forming autophagosome but dissociates", "autophagosome but dissociates from", "but dissociates from completed", "dissociates from completed autophagosomes", "completed autophagosomes geng", "autophagosomes geng &", "geng & klionski 2008", "& klionski 2008 .", "klionski 2008 . the", "2008 . the second", ". the second ubiquitin", "the second ubiquitin like", "second ubiquitin like reaction", "ubiquitin like reaction involves", "like reaction involves the", "reaction involves the conjugation", "involves the conjugation of", "the conjugation of ubiquitin", "conjugation of ubiquitin like", "of ubiquitin like molecules", "ubiquitin like molecules of", "like molecules of the", "molecules of the lc3", "of the lc3 family", "lc3 family weidberg", "family weidberg et", "weidberg et al. 2010", "al. 2010 . lc3", "2010 . lc3 proteins", ". lc3 proteins are", "lc3 proteins are conjugated", "proteins are conjugated through", "are conjugated through their", "conjugated through their c", "through their c terminal", "their c terminal glycine", "c terminal glycine residues", "terminal glycine residues with", "glycine residues with pe", "residues with pe by", "with pe by the", "pe by the e1", "by the e1 like", "the e1 like atg7", "e1 like atg7 and", "like atg7 and e2", "atg7 and e2 like", "and e2 like atg3.", "e2 like atg3. this", "like atg3. this allows", "atg3. this allows lc3", "this allows lc3 proteins", "allows lc3 proteins to", "lc3 proteins to associate", "proteins to associate with", "to associate with the", "associate with the autophagosome", "with the autophagosome membrane.", "the autophagosome membrane.

the", "autophagosome membrane.

the atg12:atg5:atg16l1", "membrane.

the atg12:atg5:atg16l1 complex", "atg12:atg5:atg16l1 complex mizushima", "complex mizushima et", "2011 acts as", "acts as an e3", "as an e3 like", "an e3 like enzyme", "e3 like enzyme for", "like enzyme for the", "enzyme for the conjugation", "for the conjugation of", "the conjugation of lc3", "conjugation of lc3 family", "of lc3 family proteins", "family proteins mammalian", "proteins mammalian homologues", "mammalian homologues of yeast", "homologues of yeast atg8", "yeast atg8 to", "atg8 to phosphatidylethanolamine", "to phosphatidylethanolamine pe", "pe hanada", "hanada et al. 2007", "al. 2007 fujita", "2007 fujita et", "fujita et al. 2008", "al. 2008 . lc3", "2008 . lc3 pe", ". lc3 pe can", "lc3 pe can be", "pe can be deconjugated", "can be deconjugated by", "be deconjugated by the", "deconjugated by the protease", "by the protease atg4", "protease atg4 li", "atg4 li et", "li et al. 2011", "al. 2011 2012", "2011 2012 .", "2012 . atg4 is", ". atg4 is also", "atg4 is also responsible", "is also responsible for", "also responsible for priming", "responsible for priming lc3", "for priming lc3 proteins", "priming lc3 proteins by", "lc3 proteins by cleaving", "proteins by cleaving the", "by cleaving the c", "cleaving the c terminus", "the c terminus to", "c terminus to expose", "terminus to expose a", "to expose a glycine", "expose a glycine residue", "glycine residue kirisako", "residue kirisako et", "et al 2000", "2000 scherz shouval", "scherz shouval et al.", "shouval et al. 2007", "al. 2007 . lc3", "2007 . lc3 proteins", ". lc3 proteins remain", "lc3 proteins remain associated", "proteins remain associated with", "remain associated with autophagosomes", "associated with autophagosomes until", "with autophagosomes until they", "autophagosomes until they fuse", "until they fuse with", "they fuse with lysosomes.", "fuse with lysosomes. the", "with lysosomes. the lc3", "lysosomes. the lc3 like", "the lc3 like proteins", "lc3 like proteins inside", "like proteins inside the", "proteins inside the resulting", "inside the resulting autolysosomes", "the resulting autolysosomes are", "resulting autolysosomes are degraded", "are degraded while", "degraded while those", "while those on the", "those on the cytoplasmic", "on the cytoplasmic surface", "the cytoplasmic surface are", "cytoplasmic surface are delipidated", "surface are delipidated and", "are delipidated and recycled.", "delipidated and recycled. atg5:atg12:atg16l1", "and recycled. atg5:atg12:atg16l1 positive", "recycled. atg5:atg12:atg16l1 positive lc3", "atg5:atg12:atg16l1 positive lc3 negative", "positive lc3 negative vesicles", "lc3 negative vesicles represent", "negative vesicles represent pre", "vesicles represent pre autophagosomal", "represent pre autophagosomal structures", "autophagosomal structures pre", "structures pre phagophores", "pre phagophores and possibly", "phagophores and possibly early", "and possibly early phagophores", "phagophores atg5:atg12:atg16l1", "atg5:atg12:atg16l1 positive lc3 positive", "positive lc3 positive structures", "lc3 positive structures can", "positive structures can be", "structures can be considered", "can be considered to", "be considered to be", "considered to be phagophores", "be phagophores and", "phagophores and atg5:atg12:atg16l1", "and atg5:atg12:atg16l1 negative lc3", "atg5:atg12:atg16l1 negative lc3 positive", "negative lc3 positive vesicles", "lc3 positive vesicles can", "positive vesicles can be", "vesicles can be regarded", "can be regarded as", "be regarded as mature", "regarded as mature autophagosomes", "mature autophagosomes tandia", "autophagosomes tandia et", "tandia et al. 2011", "et al. 2011 .

phagophore", "al. 2011 .

phagophore expansion", "2011 .

phagophore expansion is", ".

phagophore expansion is probably", "uptake from endomembranes as", "from endomembranes as well", "endomembranes as well as", "as well as from", "well as from semiautonomous", "as from semiautonomous organelles", "semiautonomous organelles lamb", "& yoshimori 2014 .

the", "yoshimori 2014 .

the mechanisms", "2014 .

the mechanisms involved", ".

the mechanisms involved in", "mechanisms involved in the", "involved in the closure", "in the closure of", "the closure of the", "closure of the phagophore", "the phagophore membrane are", "phagophore membrane are poorly", "membrane are poorly understood.", "are poorly understood. as", "poorly understood. as the", "understood. as the phagophore", "as the phagophore is", "the phagophore is a", "phagophore is a double", "is a double membraned", "a double membraned structure", "membraned structure its", "structure its closure", "its closure involves the", "closure involves the fusion", "involves the fusion of", "the fusion of a", "fusion of a narrow", "of a narrow opening", "narrow opening a", "opening a process", "process that is distinct", "that is distinct from", "is distinct from other", "distinct from other membrane", "from other membrane fusion", "other membrane fusion events", "fusion events carlsson", "events carlsson &", "simonsen 2015 . the", "2015 . the topology", ". the topology of", "the topology of the", "topology of the phagophore", "of the phagophore is", "the phagophore is similar", "phagophore is similar to", "is similar to that", "similar to that of", "to that of cytokinesis", "of cytokinesis viral", "cytokinesis viral budding", "viral budding or multivesicular", "budding or multivesicular body", "multivesicular body mvb", "mvb formation. these", "formation. these processes rely", "these processes rely on", "processes rely on the", "rely on the endosomal", "on the endosomal sorting", "the endosomal sorting complex", "endosomal sorting complex required", "sorting complex required for", "complex required for transport", "for transport escrt", "escrt rusten", "rusten et al. 2012", "al. 2012 . escrt", "2012 . escrt and", ". escrt and associated", "escrt and associated proteins", "and associated proteins facilitate", "associated proteins facilitate membrane", "proteins facilitate membrane budding", "facilitate membrane budding away", "membrane budding away from", "budding away from the", "away from the cytosol", "from the cytosol and", "the cytosol and subsequent", "cytosol and subsequent cleavage", "and subsequent cleavage of", "subsequent cleavage of the", "cleavage of the bud", "of the bud neck", "bud neck hurley", "neck hurley &", "hurley & hanson 2010", "& hanson 2010 .", "hanson 2010 . several", "2010 . several studies", ". several studies have", "several studies have shown", "studies have shown that", "have shown that depletion", "shown that depletion of", "that depletion of escrt", "depletion of escrt subunits", "of escrt subunits or", "escrt subunits or the", "subunits or the regulatory", "or the regulatory atpase", "the regulatory atpase vps4", "regulatory atpase vps4 causes", "atpase vps4 causes an", "vps4 causes an accumulation", "causes an accumulation of", "an accumulation of autophagosomes", "of autophagosomes filimonenko", "autophagosomes filimonenko et", "filimonenko et al. 2007", "al. 2007 rusten", "2007 rusten et", "rusten et al. 2007", "al. 2007 but", "2007 but it", "is not clear whether", "not clear whether escrts", "clear whether escrts are", "whether escrts are required", "escrts are required for", "are required for autophagosome", "required for autophagosome closure", "for autophagosome closure or", "autophagosome closure or for", "closure or for autophagosome", "or for autophagosome to", "for autophagosome to endosome", "autophagosome to endosome fusion.", "to endosome fusion. uvrag", "endosome fusion. uvrag is", "fusion. uvrag is also", "uvrag is also involved", "is also involved in", "also involved in the", "involved in the maturation", "in the maturation step", "maturation step recruiting", "step recruiting proteins", "recruiting proteins that bring", "proteins that bring about", "that bring about membrane", "bring about membrane fusion", "about membrane fusion such", "membrane fusion such as", "fusion such as the", "such as the class", "as the class c", "the class c vps", "class c vps proteins", "vps proteins which", "proteins which activate", "which activate rab7 thereby", "activate rab7 thereby promoting", "rab7 thereby promoting fusion", "thereby promoting fusion with", "promoting fusion with late", "fusion with late endosomes", "with late endosomes and", "late endosomes and lysosomes", "and lysosomes liang", "lysosomes liang et", "macroautophagy hereafter referred to", "hereafter referred to as autophagy", "to as autophagy acts", "as autophagy acts as", "autophagy acts as a", "acts as a buffer against", "as a buffer against starvation", "a buffer against starvation by", "buffer against starvation by liberating", "against starvation by liberating building", "starvation by liberating building materials", "by liberating building materials and", "liberating building materials and energy", "building materials and energy sources", "materials and energy sources from", "and energy sources from cellular", "energy sources from cellular components.", "sources from cellular components. it", "from cellular components. it has", "cellular components. it has additional", "components. it has additional roles", "it has additional roles in", "has additional roles in embryonic", "additional roles in embryonic development", "in embryonic development removal", "embryonic development removal of", "development removal of apoptotic", "removal of apoptotic cells or", "of apoptotic cells or organelles", "cells or organelles antigen", "or organelles antigen presentation", "antigen presentation protection against", "presentation protection against toxins", "protection against toxins and as", "against toxins and as a", "toxins and as a degradation", "and as a degradation route", "as a degradation route for", "a degradation route for aggregate", "degradation route for aggregate prone", "route for aggregate prone proteins", "for aggregate prone proteins and", "aggregate prone proteins and infectious", "prone proteins and infectious agents.", "proteins and infectious agents. the", "and infectious agents. the dysregulation", "infectious agents. the dysregulation of", "agents. the dysregulation of autophagy", "the dysregulation of autophagy is", "dysregulation of autophagy is involved", "of autophagy is involved in", "autophagy is involved in several", "is involved in several human", "involved in several human diseases", "several human diseases for", "human diseases for example", "for example crohn's disease", "crohn's disease cancer and", "disease cancer and neurodegeneration", "cancer and neurodegeneration ravikumar", "and neurodegeneration ravikumar et", "neurodegeneration ravikumar et al.", "ravikumar et al. 2010 .
autophagy", "et al. 2010 .
autophagy is", "al. 2010 .
autophagy is highly", "2010 .
autophagy is highly conserved", ".
autophagy is highly conserved from", "is highly conserved from yeast", "highly conserved from yeast to", "conserved from yeast to humans", "yeast to humans much", "to humans much of", "humans much of the", "much of the machinery was", "of the machinery was first", "the machinery was first identified", "machinery was first identified in", "was first identified in yeast", "identified in yeast see", "in yeast see klionsky", "yeast see klionsky et", "see klionsky et al. 2011", "klionsky et al. 2011 .", "et al. 2011 . initially", "2011 . initially double", ". initially double membraned", "initially double membraned cup", "double membraned cup shaped structures", "membraned cup shaped structures called", "cup shaped structures called the", "shaped structures called the isolation", "structures called the isolation membrane", "called the isolation membrane or", "the isolation membrane or phagophore", "isolation membrane or phagophore engulf", "membrane or phagophore engulf portions", "or phagophore engulf portions of", "phagophore engulf portions of cytoplasm.", "engulf portions of cytoplasm. the", "portions of cytoplasm. the membranes", "of cytoplasm. the membranes fuse", "cytoplasm. the membranes fuse to", "the membranes fuse to form", "membranes fuse to form the", "fuse to form the autophagosome.", "to form the autophagosome. in", "form the autophagosome. in yeast", "the autophagosome. in yeast cells", "in yeast cells autophagosomes", "yeast cells autophagosomes are", "cells autophagosomes are formed", "autophagosomes are formed at the", "are formed at the phagophore", "formed at the phagophore assembly", "at the phagophore assembly site", "phagophore assembly site pas", "site pas next", "pas next to the", "next to the vacuole. in", "to the vacuole. in mammals", "vacuole. in mammals autophagosomes", "in mammals autophagosomes appear", "mammals autophagosomes appear throughout", "autophagosomes appear throughout the cytoplasm", "appear throughout the cytoplasm then", "throughout the cytoplasm then move", "the cytoplasm then move along", "cytoplasm then move along microtubules", "then move along microtubules towards", "move along microtubules towards the", "along microtubules towards the microtubule", "microtubules towards the microtubule organising", "towards the microtubule organising centre.", "the microtubule organising centre. this", "microtubule organising centre. this transport", "organising centre. this transport requires", "centre. this transport requires microtubules", "this transport requires microtubules and", "transport requires microtubules and the", "requires microtubules and the function", "microtubules and the function of", "and the function of dynein", "the function of dynein motor", "function of dynein motor proteins", "dynein motor proteins depolymerization", "motor proteins depolymerization of", "proteins depolymerization of microtubules", "depolymerization of microtubules or inhibition", "of microtubules or inhibition of", "microtubules or inhibition of dynein", "or inhibition of dynein dependent", "inhibition of dynein dependent transport", "of dynein dependent transport results", "dynein dependent transport results in", "dependent transport results in inhibition", "transport results in inhibition of", "results in inhibition of autophagy", "inhibition of autophagy kochl", "of autophagy kochl et", "autophagy kochl et al.", "et al. 2006 kimura", "al. 2006 kimura et", "2006 kimura et al.", "kimura et al. 2008 .", "et al. 2008 . autophagosomes", "al. 2008 . autophagosomes fuse", "2008 . autophagosomes fuse with", ". autophagosomes fuse with lysosomes", "autophagosomes fuse with lysosomes forming", "fuse with lysosomes forming autolysosomes", "with lysosomes forming autolysosomes whose", "lysosomes forming autolysosomes whose contents", "forming autolysosomes whose contents are", "autolysosomes whose contents are degraded", "whose contents are degraded by", "contents are degraded by lysosomal", "are degraded by lysosomal hydrolases", "by lysosomal hydrolases mizushima", "lysosomal hydrolases mizushima et", "hydrolases mizushima et al.", "mizushima et al. 2011 .

the", "et al. 2011 .

the origins", "al. 2011 .

the origins of", "2011 .

the origins of the", ".

the origins of the autophagosomal", "origins of the autophagosomal membrane", "of the autophagosomal membrane and", "the autophagosomal membrane and the", "membrane and the incorporation", "and the incorporation of", "the incorporation of existing", "incorporation of existing membrane material", "of existing membrane material have", "existing membrane material have been", "membrane material have been extensively", "material have been extensively debated.", "have been extensively debated. the", "been extensively debated. the endoplasmic", "extensively debated. the endoplasmic reticulum", "the endoplasmic reticulum er", "mitochondria mitochondria associated er", "associated er membranes mams", "mams the golgi", "the golgi the plasma", "golgi the plasma membrane", "the plasma membrane and recycling", "plasma membrane and recycling endosomes", "membrane and recycling endosomes have", "and recycling endosomes have all", "recycling endosomes have all been", "endosomes have all been implicated", "have all been implicated in", "all been implicated in the", "been implicated in the nucleation", "implicated in the nucleation of", "in the nucleation of the", "the nucleation of the isolation", "nucleation of the isolation membrane", "of the isolation membrane and", "the isolation membrane and subsequent", "isolation membrane and subsequent growth", "membrane and subsequent growth of", "and subsequent growth of the", "subsequent growth of the membrane", "of the membrane lamb", "the membrane lamb et", "membrane lamb et al.", "lamb et al. 2013 .", "et al. 2013 . recently", "al. 2013 . recently 3d", "2013 . recently 3d tomographic", ". recently 3d tomographic imaging", "recently 3d tomographic imaging of", "3d tomographic imaging of isolation", "tomographic imaging of isolation membranes", "imaging of isolation membranes has", "of isolation membranes has shown", "isolation membranes has shown the", "membranes has shown the cup", "has shown the cup shaped", "shown the cup shaped isolation", "the cup shaped isolation membrane", "cup shaped isolation membrane tightly", "shaped isolation membrane tightly sandwiched", "isolation membrane tightly sandwiched between", "membrane tightly sandwiched between two", "tightly sandwiched between two sheets", "sandwiched between two sheets of", "between two sheets of er", "two sheets of er and", "sheets of er and physically", "of er and physically connected", "er and physically connected to", "and physically connected to the", "physically connected to the er", "connected to the er through", "to the er through a", "the er through a narrow", "er through a narrow membrane", "through a narrow membrane tube", "narrow membrane tube hayashi", "membrane tube hayashi nishino", "tube hayashi nishino et", "hayashi nishino et al. 2009", "et al. 2009 yla", "al. 2009 yla anttila", "2009 yla anttila et", "yla anttila et al. 2009", "anttila et al. 2009 .", "et al. 2009 . this", "al. 2009 . this suggests", "2009 . this suggests that", ". this suggests that isolation", "this suggests that isolation membrane", "suggests that isolation membrane formation", "that isolation membrane formation and", "isolation membrane formation and elongation", "membrane formation and elongation are", "formation and elongation are guided", "and elongation are guided by", "elongation are guided by adjacent", "are guided by adjacent er", "guided by adjacent er sheets", "adjacent er sheets supporting", "er sheets supporting the", "sheets supporting the now", "supporting the now prevalent 'er", "the now prevalent 'er cradle'", "now prevalent 'er cradle' model", "'er cradle' model which", "cradle' model which suggests", "model which suggests that", "which suggests that the isolation", "suggests that the isolation membrane", "that the isolation membrane arises", "the isolation membrane arises from", "isolation membrane arises from the", "membrane arises from the er", "from the er hayashi", "the er hayashi nishino", "er hayashi nishino et", "et al. 2009 shibutani", "al. 2009 shibutani &", "2009 shibutani & yoshimori", "shibutani & yoshimori 2014 .

autophagy", "& yoshimori 2014 .

autophagy is", "yoshimori 2014 .

autophagy is tightly", "2014 .

autophagy is tightly regulated.", ".

autophagy is tightly regulated. the", "is tightly regulated. the induction", "tightly regulated. the induction of", "regulated. the induction of autophagy", "the induction of autophagy in", "induction of autophagy in response", "of autophagy in response to", "autophagy in response to starvation", "in response to starvation is", "response to starvation is partly", "to starvation is partly mediated", "starvation is partly mediated by", "is partly mediated by inactivation", "partly mediated by inactivation of", "mediated by inactivation of the", "by inactivation of the mammalian", "inactivation of the mammalian target", "of the mammalian target of", "the mammalian target of rapamycin", "target of rapamycin mtor", "mtor noda &", "& ohsumi 1998 and", "ohsumi 1998 and activation", "1998 and activation of", "and activation of jun n", "activation of jun n terminal", "of jun n terminal kinase", "n terminal kinase jnk", "jnk while energy", "while energy loss induces autophagy", "energy loss induces autophagy by", "loss induces autophagy by activation", "induces autophagy by activation of", "autophagy by activation of amp", "by activation of amp kinase", "of amp kinase ampk", "amp kinase ampk .", "kinase ampk . other", "ampk . other pathways regulating", ". other pathways regulating autophagy", "other pathways regulating autophagy are", "pathways regulating autophagy are regulated", "regulating autophagy are regulated by", "autophagy are regulated by calcium", "regulated by calcium cyclic", "by calcium cyclic amp", "cyclic amp calpains and", "amp calpains and the", "calpains and the inositol trisphosphate", "the inositol trisphosphate ip3", "trisphosphate ip3 receptor", "ip3 receptor rubinsztein", "receptor rubinsztein et al.", "rubinsztein et al. 2012 .", "et al. 2012 .

in", "al. 2012 .

in mammals", ".

in mammals two", "

in mammals two complexes", "mammals two complexes cooperatively", "two complexes cooperatively produce the", "complexes cooperatively produce the isolation", "cooperatively produce the isolation membrane.", "produce the isolation membrane. the", "the isolation membrane. the ulk", "isolation membrane. the ulk complex", "membrane. the ulk complex consists", "the ulk complex consists of", "ulk complex consists of ulk1/2", "consists of ulk1/2 atg13", "and atg101 alers et", "atg101 alers et al.", "alers et al. 2012 .", "et al. 2012 . the", "al. 2012 . the pik3c3", "2012 . the pik3c3 containing", ". the pik3c3 containing beclin", "the pik3c3 containing beclin 1", "pik3c3 containing beclin 1 complex", "containing beclin 1 complex consists", "beclin 1 complex consists of", "1 complex consists of pik3c3", "consists of pik3c3 vps34", "pik3r4 p150 vps15", "p150 vps15 and", "barkor matsunaga et", "et al. 2009 zhong", "al. 2009 zhong et", "2009 zhong et al.", "zhong et al. 2009 .", "et al. 2009 . a", "al. 2009 . a similar", "2009 . a similar complex", ". a similar complex where", "a similar complex where atg14", "similar complex where atg14 is", "complex where atg14 is replaced", "where atg14 is replaced by", "atg14 is replaced by uvrag", "is replaced by uvrag functions", "replaced by uvrag functions later", "by uvrag functions later in", "uvrag functions later in autophagosome", "functions later in autophagosome maturation", "later in autophagosome maturation and", "in autophagosome maturation and endocytic", "autophagosome maturation and endocytic traffic", "and endocytic traffic itakura", "endocytic traffic itakura et", "traffic itakura et al.", "et al. 2008 liang", "al. 2008 liang et", "2008 liang et al.", "liang et al. 2008 .", "et al. 2008 . binding", "al. 2008 . binding of", "2008 . binding of kiaa0226", ". binding of kiaa0226 to", "binding of kiaa0226 to this", "of kiaa0226 to this complex", "kiaa0226 to this complex negatively", "to this complex negatively regulates", "this complex negatively regulates the", "complex negatively regulates the maturation", "negatively regulates the maturation process", "the maturation process matsunaga", "maturation process matsunaga et", "process matsunaga et al.", "matsunaga et al. 2009 .", "et al. 2009 . the", "al. 2009 . the ulk", "2009 . the ulk and", ". the ulk and beclin", "the ulk and beclin 1", "ulk and beclin 1 complexes", "and beclin 1 complexes are", "beclin 1 complexes are recruited", "1 complexes are recruited to", "complexes are recruited to specific", "are recruited to specific autophagosome", "recruited to specific autophagosome nucleation", "to specific autophagosome nucleation regions", "specific autophagosome nucleation regions where", "autophagosome nucleation regions where they", "nucleation regions where they stimulate", "regions where they stimulate phosphatidylinositol", "where they stimulate phosphatidylinositol 3", "they stimulate phosphatidylinositol 3 phosphate", "phosphatidylinositol 3 phosphate pi3p", "phosphate pi3p production", "pi3p production and facilitate", "production and facilitate the elongation", "and facilitate the elongation and", "facilitate the elongation and initial", "the elongation and initial membrane", "elongation and initial membrane curvature", "and initial membrane curvature of", "initial membrane curvature of the", "membrane curvature of the phagophore", "curvature of the phagophore membrane", "the phagophore membrane carlsson", "phagophore membrane carlsson &", "membrane carlsson & simonsen", "carlsson & simonsen 2015 .

the", "& simonsen 2015 .

the ulk", "simonsen 2015 .

the ulk complex", "2015 .

the ulk complex is", ".

the ulk complex is considered", "ulk complex is considered the", "complex is considered the most", "is considered the most upstream", "considered the most upstream component", "the most upstream component of", "most upstream component of the", "upstream component of the mammalian", "component of the mammalian autophagy", "of the mammalian autophagy pathway", "mammalian autophagy pathway itakura", "autophagy pathway itakura &", "pathway itakura & mizushima", "mizushima 2010 acting", "2010 acting as", "acting as an integrator of", "as an integrator of the", "an integrator of the autophagy", "integrator of the autophagy signals", "of the autophagy signals downstream", "the autophagy signals downstream of", "autophagy signals downstream of mtorc1.", "signals downstream of mtorc1. it", "downstream of mtorc1. it is", "of mtorc1. it is not", "mtorc1. it is not fully", "it is not fully understood", "is not fully understood how", "not fully understood how ulk1", "fully understood how ulk1 is", "understood how ulk1 is modulated", "how ulk1 is modulated in", "ulk1 is modulated in response", "is modulated in response to", "modulated in response to environmental", "in response to environmental cues.", "response to environmental cues. phosphorylation", "to environmental cues. phosphorylation plays", "environmental cues. phosphorylation plays an", "cues. phosphorylation plays an essential", "phosphorylation plays an essential role", "an essential role dunlop", "essential role dunlop &", "role dunlop & tee", "& tee 2013 but", "tee 2013 but it", "2013 but it is", "but it is not clear", "it is not clear how", "is not clear how phosphorylation", "not clear how phosphorylation regulates", "clear how phosphorylation regulates ulk1", "how phosphorylation regulates ulk1 activities", "regulates ulk1 activities ravikumar", "ulk1 activities ravikumar et", "activities ravikumar et al.", "ravikumar et al. 2010 .", "et al. 2010 . ulk1", "al. 2010 . ulk1 kinase", "2010 . ulk1 kinase activity", ". ulk1 kinase activity is", "ulk1 kinase activity is required", "kinase activity is required for", "activity is required for autophagy", "required for autophagy but", "for autophagy but the", "autophagy but the substrate", "the substrate s of", "substrate s of ulk1", "s of ulk1 that", "of ulk1 that mediate its", "ulk1 that mediate its autophagic", "that mediate its autophagic function", "mediate its autophagic function are", "its autophagic function are not", "autophagic function are not certain.", "function are not certain. ulk1", "are not certain. ulk1 may", "not certain. ulk1 may also", "certain. ulk1 may also have", "ulk1 may also have kinase", "may also have kinase independent", "also have kinase independent functions", "have kinase independent functions in", "kinase independent functions in autophagy", "functions in autophagy wong", "in autophagy wong et", "autophagy wong et al.", "wong et al. 2013 .", "et al. 2013 .

", "al. 2013 .

pik3c3", ".

pik3c3 vps34", "pik3c3 vps34 is", "vps34 is a class", "is a class iii phosphatidylinositol", "a class iii phosphatidylinositol 3", "class iii phosphatidylinositol 3 kinase", "iii phosphatidylinositol 3 kinase that", "phosphatidylinositol 3 kinase that produces", "3 kinase that produces pi3p.", "kinase that produces pi3p. it", "that produces pi3p. it is", "produces pi3p. it is essential", "pi3p. it is essential for", "it is essential for the", "is essential for the early", "essential for the early stages", "for the early stages of", "the early stages of autophagy", "early stages of autophagy and", "stages of autophagy and colocalizes", "of autophagy and colocalizes strongly", "autophagy and colocalizes strongly with", "and colocalizes strongly with early", "colocalizes strongly with early autophagosome", "strongly with early autophagosome markers", "early autophagosome markers axe", "autophagosome markers axe et", "markers axe et al.", "axe et al. 2008 .", "et al. 2008 . becn1", "al. 2008 . becn1 binds", "2008 . becn1 binds several", ". becn1 binds several further", "becn1 binds several further proteins", "binds several further proteins that", "several further proteins that affect", "further proteins that affect autophagosome", "proteins that affect autophagosome formation.", "that affect autophagosome formation. partners", "affect autophagosome formation. partners that", "autophagosome formation. partners that induce", "formation. partners that induce autophagy", "partners that induce autophagy include", "that induce autophagy include ambra1", "autophagy include ambra1 fimia", "include ambra1 fimia et", "ambra1 fimia et al.", "al. 2007 uvrag", "uvrag liang et al.", "et al. 2006 and", "al. 2006 and sh3glb1", "and sh3glb1 takahashi et", "sh3glb1 takahashi et al.", "takahashi et al. 2007 .", "et al. 2007 . binding", "al. 2007 . binding of", "2007 . binding of bcl2", ". binding of bcl2 or", "binding of bcl2 or bcl2l1", "bcl2 or bcl2l1 bcl", "or bcl2l1 bcl xl", "bcl xl inhibit autophagy", "inhibit autophagy pattingre et", "autophagy pattingre et al.", "et al. 2005 ciechomska", "al. 2005 ciechomska et", "2005 ciechomska et al.", "ciechomska et al. 2009 .", "al. 2009 . the inositol", "2009 . the inositol 1", ". the inositol 1 4", "the inositol 1 4 5", "inositol 1 4 5 trisphosphate", "1 4 5 trisphosphate receptor", "4 5 trisphosphate receptor complex", "5 trisphosphate receptor complex that", "trisphosphate receptor complex that binds", "receptor complex that binds bcl2", "complex that binds bcl2 also", "that binds bcl2 also interacts", "binds bcl2 also interacts with", "bcl2 also interacts with becn1", "interacts with becn1 inhibiting", "with becn1 inhibiting autophagy", "inhibiting autophagy vincencio et", "autophagy vincencio et al.", "vincencio et al. 2009 .", "et al. 2009 . cisd2", "2009 . cisd2 nutrient", ". cisd2 nutrient deprivation", "cisd2 nutrient deprivation autophagy", "nutrient deprivation autophagy factor 1", "autophagy factor 1 naf1", "naf1 a component", "a component in the ip3r", "component in the ip3r complex", "the ip3r complex interacts", "ip3r complex interacts with", "complex interacts with bcl2", "interacts with bcl2 at the", "with bcl2 at the er", "bcl2 at the er and", "at the er and stabilizes", "the er and stabilizes the", "er and stabilizes the bcl2", "and stabilizes the bcl2 becn1", "stabilizes the bcl2 becn1 interaction", "bcl2 becn1 interaction chang", "becn1 interaction chang et", "interaction chang et al.", "chang et al. 2010 .", "et al. 2010 . starvation", "al. 2010 . starvation leads", "2010 . starvation leads to", ". starvation leads to activation", "starvation leads to activation of", "leads to activation of c", "to activation of c jun", "activation of c jun nh2", "of c jun nh2 terminal", "c jun nh2 terminal kinase", "jun nh2 terminal kinase 1", "terminal kinase 1 jnk1", "jnk1 which results", "which results in the phosphorylation", "results in the phosphorylation of", "in the phosphorylation of bcl2", "the phosphorylation of bcl2 and", "phosphorylation of bcl2 and bcl2l1", "bcl2 and bcl2l1 which", "and bcl2l1 which release", "bcl2l1 which release their", "which release their binding to", "release their binding to becn1", "their binding to becn1 and", "binding to becn1 and thus", "to becn1 and thus induces", "becn1 and thus induces autophagosome", "and thus induces autophagosome formation", "induces autophagosome formation wei", "autophagosome formation wei et", "formation wei et al.", "wei et al. 2008 .", "et al. 2008 .

ambra1", "al. 2008 .

ambra1 can", "2008 .

ambra1 can simultaneously", ".

ambra1 can simultaneously bind", "

ambra1 can simultaneously bind dynein", "can simultaneously bind dynein and", "simultaneously bind dynein and the", "bind dynein and the beclin", "dynein and the beclin 1", "and the beclin 1 complex.", "beclin 1 complex. during", "1 complex. during nutrient", "complex. during nutrient starvation", "during nutrient starvation ambra1", "nutrient starvation ambra1 is", "starvation ambra1 is phosphorylated", "ambra1 is phosphorylated in a", "is phosphorylated in a ulk1", "phosphorylated in a ulk1 dependent", "in a ulk1 dependent manner", "ulk1 dependent manner di", "dependent manner di bartolomeo", "manner di bartolomeo et", "di bartolomeo et al. 2010", "bartolomeo et al. 2010 .", "et al. 2010 . this", "al. 2010 . this phosphorylation", "2010 . this phosphorylation releases", ". this phosphorylation releases ambra1", "this phosphorylation releases ambra1 associated", "phosphorylation releases ambra1 associated beclin", "releases ambra1 associated beclin 1", "ambra1 associated beclin 1 complexes", "associated beclin 1 complexes from", "beclin 1 complexes from dynein", "1 complexes from dynein and", "complexes from dynein and the", "from dynein and the microtubule", "dynein and the microtubule network", "the microtubule network freeing", "microtubule network freeing the", "network freeing the complex", "freeing the complex to translocate", "the complex to translocate to", "complex to translocate to autophagy", "to translocate to autophagy initiation", "translocate to autophagy initiation sites", "autophagy initiation sites di", "initiation sites di bartolomeo", "sites di bartolomeo et", "et al. 2010 .

a", "al. 2010 .

a characteristic", "2010 .

a characteristic of", ".

a characteristic of this", "

a characteristic of this early", "characteristic of this early phase", "of this early phase of", "this early phase of autophagosome", "early phase of autophagosome formation", "phase of autophagosome formation is", "of autophagosome formation is the", "autophagosome formation is the formation", "formation is the formation of", "is the formation of pi3p", "the formation of pi3p enriched", "formation of pi3p enriched er", "of pi3p enriched er associated", "pi3p enriched er associated structures", "enriched er associated structures called", "er associated structures called omegasomes", "structures called omegasomes axe", "called omegasomes axe et", "omegasomes axe et al.", "et al. 2008 or", "al. 2008 or cradles", "or cradles hayashi nishino", "cradles hayashi nishino et", "nishino et al. 2009 .", "et al. 2009 . omegasomes", "al. 2009 . omegasomes appear", "2009 . omegasomes appear to", ". omegasomes appear to concentrate", "omegasomes appear to concentrate at", "appear to concentrate at or", "to concentrate at or near", "concentrate at or near the", "at or near the connected", "or near the connected mitochondria", "near the connected mitochondria associated", "the connected mitochondria associated er", "connected mitochondria associated er membrane", "associated er membrane hamasaki", "er membrane hamasaki et", "membrane hamasaki et al.", "hamasaki et al. 2013 .", "et al. 2013 . however", "2013 . however the", ". however the phagophore", "however the phagophore also", "the phagophore also can incorporate", "phagophore also can incorporate existing", "also can incorporate existing material", "can incorporate existing material from", "incorporate existing material from other", "existing material from other membrane", "material from other membrane sources", "from other membrane sources such", "other membrane sources such as", "membrane sources such as er", "sources such as er exit", "such as er exit sites", "er exit sites eres", "eres the er", "the er golgi intermediate compartment", "golgi intermediate compartment ergic", "ergic the golgi", "and recycling endosomes carlsson", "recycling endosomes carlsson &", "endosomes carlsson & simonsen", "carlsson & simonsen 2015 .", "& simonsen 2015 . omegasomes", "simonsen 2015 . omegasomes lead", "2015 . omegasomes lead to", ". omegasomes lead to the", "omegasomes lead to the formation", "lead to the formation of", "to the formation of the", "the formation of the isolation", "formation of the isolation membrane", "of the isolation membrane or", "membrane or phagophore which", "or phagophore which is", "phagophore which is thought", "which is thought to form", "is thought to form de", "thought to form de novo", "to form de novo by", "form de novo by an", "de novo by an unknown", "novo by an unknown mechanism", "an unknown mechanism simonsen", "unknown mechanism simonsen &", "mechanism simonsen & stenmark", "& stenmark 2008 roberts", "stenmark 2008 roberts &", "2008 roberts & ktistakis", "roberts & ktistakis 2013 .", "& ktistakis 2013 . phagophore", "ktistakis 2013 . phagophore expansion", "2013 . phagophore expansion is", ". phagophore expansion is probably", "phagophore expansion is probably mediated", "expansion is probably mediated by", "is probably mediated by membrane", "probably mediated by membrane uptake", "mediated by membrane uptake from", "by membrane uptake from endomembranes", "membrane uptake from endomembranes and", "uptake from endomembranes and semi", "from endomembranes and semi autonomous", "endomembranes and semi autonomous organelles", "semi autonomous organelles lamb", "autonomous organelles lamb et", "organelles lamb et al.", "et al. 2013 shibutani", "al. 2013 shibutani &", "2013 shibutani & yoshimori", "shibutani & yoshimori 2014 .

atg9", "& yoshimori 2014 .

atg9 is", "yoshimori 2014 .

atg9 is a", "2014 .

atg9 is a direct", ".

atg9 is a direct target", "is a direct target of", "a direct target of ulk1.", "direct target of ulk1. in", "target of ulk1. in nutrient", "of ulk1. in nutrient rich", "ulk1. in nutrient rich conditions", "in nutrient rich conditions mammalian", "nutrient rich conditions mammalian atg9", "rich conditions mammalian atg9 is", "conditions mammalian atg9 is localized", "mammalian atg9 is localized to", "atg9 is localized to the", "is localized to the trans", "localized to the trans golgi", "to the trans golgi network", "the trans golgi network and", "trans golgi network and endosomes", "network and endosomes including", "and endosomes including early", "including early late and", "early late and recycling", "recycling endosomes whereas", "endosomes whereas under", "whereas under starvation conditions it", "under starvation conditions it is", "starvation conditions it is localized", "conditions it is localized to", "it is localized to autophagosomes", "localized to autophagosomes in", "to autophagosomes in a", "autophagosomes in a process", "in a process that is", "a process that is dependent", "process that is dependent on", "that is dependent on ulk1", "dependent on ulk1 young", "on ulk1 young et", "ulk1 young et al.", "young et al. 2006 .", "et al. 2006 . atg9", "al. 2006 . atg9 is", "2006 . atg9 is believed", ". atg9 is believed to", "atg9 is believed to play", "is believed to play a", "believed to play a role", "to play a role in", "play a role in the", "a role in the delivery", "role in the delivery of", "in the delivery of vesicles", "the delivery of vesicles derived", "delivery of vesicles derived from", "of vesicles derived from existing", "vesicles derived from existing membranes", "derived from existing membranes to", "from existing membranes to the", "existing membranes to the expanding", "membranes to the expanding phagophore", "the expanding phagophore lamb", "expanding phagophore lamb et", "phagophore lamb et al.", "et al. 2013 . yeast", "al. 2013 . yeast atg9", "2013 . yeast atg9 forms", ". yeast atg9 forms a", "yeast atg9 forms a complex", "atg9 forms a complex with", "forms a complex with atg2", "a complex with atg2 and", "complex with atg2 and atg18", "atg2 and atg18 reggiori", "and atg18 reggiori et", "atg18 reggiori et al.", "reggiori et al. 2004 .", "et al. 2004 .

pi3p", "al. 2004 .

pi3p produced", "2004 .

pi3p produced at", ".

pi3p produced at the", "

pi3p produced at the initiation", "produced at the initiation site", "at the initiation site is", "the initiation site is sensed", "initiation site is sensed by", "site is sensed by wipi2b", "sensed by wipi2b the", "by wipi2b the mammalian", "wipi2b the mammalian homologue", "the mammalian homologue of atg18", "homologue of atg18 polson", "of atg18 polson et", "atg18 polson et al.", "polson et al. 2010 .", "et al. 2010 . wipi2b", "al. 2010 . wipi2b then", "2010 . wipi2b then recruits", ". wipi2b then recruits atg16l1", "then recruits atg16l1 dooley", "recruits atg16l1 dooley et", "atg16l1 dooley et al.", "dooley et al. 2014 .", "et al. 2014 . there", "al. 2014 . there are", "2014 . there are four", ". there are four wipi", "there are four wipi proteins", "are four wipi proteins in", "four wipi proteins in mammalian", "wipi proteins in mammalian cells", "in mammalian cells proikas", "mammalian cells proikas cezanne", "cells proikas cezanne et", "proikas cezanne et al. 2015", "cezanne et al. 2015 .", "et al. 2015 . they", "al. 2015 . they are", "2015 . they are all", ". they are all likely", "they are all likely bind", "are all likely bind pi3p", "all likely bind pi3p and", "likely bind pi3p and be", "bind pi3p and be recruited", "pi3p and be recruited to", "and be recruited to membranes", "be recruited to membranes but", "recruited to membranes but the", "to membranes but the function", "membranes but the function of", "but the function of wipi1", "function of wipi1 3", "of wipi1 3 and", "wipi1 3 and 4", "3 and 4 in autophagy", "and 4 in autophagy is", "4 in autophagy is not", "in autophagy is not yet", "autophagy is not yet clear.", "is not yet clear. wipi4", "yet clear. wipi4 wdr45", "wipi4 wdr45 has", "wdr45 has been shown", "has been shown to bind", "been shown to bind atg2", "shown to bind atg2 and", "to bind atg2 and to", "bind atg2 and to be", "atg2 and to be involved", "and to be involved in", "to be involved in lipid", "be involved in lipid droplet", "involved in lipid droplet formation", "lipid droplet formation velikkakath", "droplet formation velikkakath et", "formation velikkakath et al.", "al. 2012 mutations", "2012 mutations in", "mutations in wipi4 have been", "in wipi4 have been shown", "wipi4 have been shown to", "have been shown to cause", "been shown to cause a", "shown to cause a neurodegenerative", "to cause a neurodegenerative disease", "a neurodegenerative disease saitsu", "neurodegenerative disease saitsu et", "disease saitsu et al.", "saitsu et al. 2013 .

the", "et al. 2013 .

the elongation", "al. 2013 .

the elongation of", "2013 .

the elongation of the", ".

the elongation of the membrane", "elongation of the membrane that", "of the membrane that will", "the membrane that will become", "membrane that will become the", "that will become the autophagosome", "will become the autophagosome is", "become the autophagosome is regulated", "the autophagosome is regulated by", "autophagosome is regulated by two", "is regulated by two ubiquitination", "regulated by two ubiquitination like", "by two ubiquitination like reactions.", "two ubiquitination like reactions. first", "like reactions. first the", "reactions. first the ubiquitin", "first the ubiquitin like", "the ubiquitin like molecule atg12", "ubiquitin like molecule atg12 is", "like molecule atg12 is conjugated", "molecule atg12 is conjugated to", "atg12 is conjugated to atg5", "is conjugated to atg5 by", "conjugated to atg5 by atg7", "atg5 by atg7 which", "by atg7 which acts", "atg7 which acts as", "which acts as an e1", "acts as an e1 like", "as an e1 like activating", "an e1 like activating enzyme", "like activating enzyme and", "activating enzyme and atg10", "and atg10 which has", "atg10 which has a", "which has a role similar", "has a role similar to", "a role similar to an", "role similar to an e2", "similar to an e2 ubiquitin", "to an e2 ubiquitin conjugating", "an e2 ubiquitin conjugating enzyme.", "e2 ubiquitin conjugating enzyme. the", "ubiquitin conjugating enzyme. the atg5:atg12", "conjugating enzyme. the atg5:atg12 complex", "enzyme. the atg5:atg12 complex then", "the atg5:atg12 complex then interacts", "atg5:atg12 complex then interacts non", "complex then interacts non covalently", "then interacts non covalently with", "interacts non covalently with atg16l1.", "non covalently with atg16l1. this", "covalently with atg16l1. this complex", "with atg16l1. this complex associates", "atg16l1. this complex associates with", "this complex associates with the", "complex associates with the forming", "associates with the forming autophagosome", "with the forming autophagosome but", "the forming autophagosome but dissociates", "forming autophagosome but dissociates from", "autophagosome but dissociates from completed", "but dissociates from completed autophagosomes", "from completed autophagosomes geng", "completed autophagosomes geng &", "autophagosomes geng & klionski", "geng & klionski 2008 .", "& klionski 2008 . the", "klionski 2008 . the second", "2008 . the second ubiquitin", ". the second ubiquitin like", "the second ubiquitin like reaction", "second ubiquitin like reaction involves", "ubiquitin like reaction involves the", "like reaction involves the conjugation", "reaction involves the conjugation of", "involves the conjugation of ubiquitin", "the conjugation of ubiquitin like", "conjugation of ubiquitin like molecules", "of ubiquitin like molecules of", "ubiquitin like molecules of the", "like molecules of the lc3", "molecules of the lc3 family", "the lc3 family weidberg", "lc3 family weidberg et", "family weidberg et al.", "weidberg et al. 2010 .", "et al. 2010 . lc3", "al. 2010 . lc3 proteins", "2010 . lc3 proteins are", ". lc3 proteins are conjugated", "lc3 proteins are conjugated through", "proteins are conjugated through their", "are conjugated through their c", "conjugated through their c terminal", "through their c terminal glycine", "their c terminal glycine residues", "c terminal glycine residues with", "terminal glycine residues with pe", "glycine residues with pe by", "residues with pe by the", "with pe by the e1", "pe by the e1 like", "by the e1 like atg7", "the e1 like atg7 and", "e1 like atg7 and e2", "like atg7 and e2 like", "atg7 and e2 like atg3.", "and e2 like atg3. this", "e2 like atg3. this allows", "like atg3. this allows lc3", "atg3. this allows lc3 proteins", "this allows lc3 proteins to", "allows lc3 proteins to associate", "lc3 proteins to associate with", "proteins to associate with the", "to associate with the autophagosome", "associate with the autophagosome membrane.", "with the autophagosome membrane.

the", "the autophagosome membrane.

the atg12:atg5:atg16l1", "autophagosome membrane.

the atg12:atg5:atg16l1 complex", "

the atg12:atg5:atg16l1 complex mizushima", "atg12:atg5:atg16l1 complex mizushima et", "complex mizushima et al.", "al. 2011 acts", "2011 acts as an", "acts as an e3 like", "as an e3 like enzyme", "an e3 like enzyme for", "e3 like enzyme for the", "like enzyme for the conjugation", "enzyme for the conjugation of", "for the conjugation of lc3", "the conjugation of lc3 family", "conjugation of lc3 family proteins", "lc3 family proteins mammalian", "family proteins mammalian homologues", "proteins mammalian homologues of", "mammalian homologues of yeast atg8", "of yeast atg8 to", "yeast atg8 to phosphatidylethanolamine", "pe hanada et", "et al. 2007 fujita", "al. 2007 fujita et", "2007 fujita et al.", "fujita et al. 2008 .", "et al. 2008 . lc3", "al. 2008 . lc3 pe", "2008 . lc3 pe can", ". lc3 pe can be", "lc3 pe can be deconjugated", "pe can be deconjugated by", "can be deconjugated by the", "be deconjugated by the protease", "deconjugated by the protease atg4", "the protease atg4 li", "protease atg4 li et", "atg4 li et al.", "et al. 2011 2012", "al. 2011 2012 .", "2011 2012 . atg4", "2012 . atg4 is also", ". atg4 is also responsible", "atg4 is also responsible for", "is also responsible for priming", "also responsible for priming lc3", "responsible for priming lc3 proteins", "for priming lc3 proteins by", "priming lc3 proteins by cleaving", "lc3 proteins by cleaving the", "proteins by cleaving the c", "by cleaving the c terminus", "cleaving the c terminus to", "the c terminus to expose", "c terminus to expose a", "terminus to expose a glycine", "to expose a glycine residue", "a glycine residue kirisako", "glycine residue kirisako et", "residue kirisako et al", "kirisako et al 2000", "al 2000 scherz", "2000 scherz shouval et", "scherz shouval et al. 2007", "shouval et al. 2007 .", "et al. 2007 . lc3", "al. 2007 . lc3 proteins", "2007 . lc3 proteins remain", ". lc3 proteins remain associated", "lc3 proteins remain associated with", "proteins remain associated with autophagosomes", "remain associated with autophagosomes until", "associated with autophagosomes until they", "with autophagosomes until they fuse", "autophagosomes until they fuse with", "until they fuse with lysosomes.", "they fuse with lysosomes. the", "fuse with lysosomes. the lc3", "with lysosomes. the lc3 like", "lysosomes. the lc3 like proteins", "the lc3 like proteins inside", "lc3 like proteins inside the", "like proteins inside the resulting", "proteins inside the resulting autolysosomes", "inside the resulting autolysosomes are", "the resulting autolysosomes are degraded", "autolysosomes are degraded while", "are degraded while those", "degraded while those on", "while those on the cytoplasmic", "those on the cytoplasmic surface", "on the cytoplasmic surface are", "the cytoplasmic surface are delipidated", "cytoplasmic surface are delipidated and", "surface are delipidated and recycled.", "are delipidated and recycled. atg5:atg12:atg16l1", "delipidated and recycled. atg5:atg12:atg16l1 positive", "and recycled. atg5:atg12:atg16l1 positive lc3", "recycled. atg5:atg12:atg16l1 positive lc3 negative", "atg5:atg12:atg16l1 positive lc3 negative vesicles", "positive lc3 negative vesicles represent", "lc3 negative vesicles represent pre", "negative vesicles represent pre autophagosomal", "vesicles represent pre autophagosomal structures", "pre autophagosomal structures pre", "autophagosomal structures pre phagophores", "structures pre phagophores and", "pre phagophores and possibly early", "phagophores and possibly early phagophores", "early phagophores atg5:atg12:atg16l1", "phagophores atg5:atg12:atg16l1 positive", "atg5:atg12:atg16l1 positive lc3 positive structures", "positive lc3 positive structures can", "lc3 positive structures can be", "positive structures can be considered", "structures can be considered to", "can be considered to be", "be considered to be phagophores", "to be phagophores and", "be phagophores and atg5:atg12:atg16l1", "phagophores and atg5:atg12:atg16l1 negative", "and atg5:atg12:atg16l1 negative lc3 positive", "atg5:atg12:atg16l1 negative lc3 positive vesicles", "negative lc3 positive vesicles can", "lc3 positive vesicles can be", "positive vesicles can be regarded", "vesicles can be regarded as", "can be regarded as mature", "be regarded as mature autophagosomes", "as mature autophagosomes tandia", "mature autophagosomes tandia et", "autophagosomes tandia et al.", "tandia et al. 2011 .

phagophore", "et al. 2011 .

phagophore expansion", "al. 2011 .

phagophore expansion is", "2011 .

phagophore expansion is probably", ".

phagophore expansion is probably mediated", "membrane uptake from endomembranes as", "uptake from endomembranes as well", "from endomembranes as well as", "endomembranes as well as from", "as well as from semiautonomous", "well as from semiautonomous organelles", "from semiautonomous organelles lamb", "semiautonomous organelles lamb et", "shibutani & yoshimori 2014 .

the", "& yoshimori 2014 .

the mechanisms", "yoshimori 2014 .

the mechanisms involved", "2014 .

the mechanisms involved in", ".

the mechanisms involved in the", "mechanisms involved in the closure", "involved in the closure of", "in the closure of the", "the closure of the phagophore", "closure of the phagophore membrane", "of the phagophore membrane are", "the phagophore membrane are poorly", "phagophore membrane are poorly understood.", "membrane are poorly understood. as", "are poorly understood. as the", "poorly understood. as the phagophore", "understood. as the phagophore is", "as the phagophore is a", "the phagophore is a double", "phagophore is a double membraned", "is a double membraned structure", "double membraned structure its", "membraned structure its closure", "structure its closure involves", "its closure involves the fusion", "closure involves the fusion of", "involves the fusion of a", "the fusion of a narrow", "fusion of a narrow opening", "a narrow opening a", "narrow opening a process", "opening a process that", "a process that is distinct", "process that is distinct from", "that is distinct from other", "is distinct from other membrane", "distinct from other membrane fusion", "from other membrane fusion events", "membrane fusion events carlsson", "fusion events carlsson &", "events carlsson & simonsen", "& simonsen 2015 . the", "simonsen 2015 . the topology", "2015 . the topology of", ". the topology of the", "the topology of the phagophore", "topology of the phagophore is", "of the phagophore is similar", "the phagophore is similar to", "phagophore is similar to that", "is similar to that of", "similar to that of cytokinesis", "that of cytokinesis viral", "of cytokinesis viral budding", "cytokinesis viral budding or", "viral budding or multivesicular body", "or multivesicular body mvb", "body mvb formation.", "mvb formation. these processes", "formation. these processes rely on", "these processes rely on the", "processes rely on the endosomal", "rely on the endosomal sorting", "on the endosomal sorting complex", "the endosomal sorting complex required", "endosomal sorting complex required for", "sorting complex required for transport", "required for transport escrt", "escrt rusten et", "rusten et al. 2012 .", "et al. 2012 . escrt", "al. 2012 . escrt and", "2012 . escrt and associated", ". escrt and associated proteins", "escrt and associated proteins facilitate", "and associated proteins facilitate membrane", "associated proteins facilitate membrane budding", "proteins facilitate membrane budding away", "facilitate membrane budding away from", "membrane budding away from the", "budding away from the cytosol", "away from the cytosol and", "from the cytosol and subsequent", "the cytosol and subsequent cleavage", "cytosol and subsequent cleavage of", "and subsequent cleavage of the", "subsequent cleavage of the bud", "cleavage of the bud neck", "the bud neck hurley", "bud neck hurley &", "neck hurley & hanson", "hurley & hanson 2010 .", "& hanson 2010 . several", "hanson 2010 . several studies", "2010 . several studies have", ". several studies have shown", "several studies have shown that", "studies have shown that depletion", "have shown that depletion of", "shown that depletion of escrt", "that depletion of escrt subunits", "depletion of escrt subunits or", "of escrt subunits or the", "escrt subunits or the regulatory", "subunits or the regulatory atpase", "or the regulatory atpase vps4", "the regulatory atpase vps4 causes", "regulatory atpase vps4 causes an", "atpase vps4 causes an accumulation", "vps4 causes an accumulation of", "causes an accumulation of autophagosomes", "accumulation of autophagosomes filimonenko", "of autophagosomes filimonenko et", "autophagosomes filimonenko et al.", "et al. 2007 rusten", "al. 2007 rusten et", "2007 rusten et al.", "et al. 2007 but", "al. 2007 but it", "2007 but it is", "it is not clear whether", "is not clear whether escrts", "not clear whether escrts are", "clear whether escrts are required", "whether escrts are required for", "escrts are required for autophagosome", "are required for autophagosome closure", "required for autophagosome closure or", "for autophagosome closure or for", "autophagosome closure or for autophagosome", "closure or for autophagosome to", "or for autophagosome to endosome", "for autophagosome to endosome fusion.", "autophagosome to endosome fusion. uvrag", "to endosome fusion. uvrag is", "endosome fusion. uvrag is also", "fusion. uvrag is also involved", "uvrag is also involved in", "is also involved in the", "also involved in the maturation", "involved in the maturation step", "the maturation step recruiting", "maturation step recruiting proteins", "step recruiting proteins that", "recruiting proteins that bring about", "proteins that bring about membrane", "that bring about membrane fusion", "bring about membrane fusion such", "about membrane fusion such as", "membrane fusion such as the", "fusion such as the class", "such as the class c", "as the class c vps", "the class c vps proteins", "c vps proteins which", "vps proteins which activate", "proteins which activate rab7", "which activate rab7 thereby promoting", "activate rab7 thereby promoting fusion", "rab7 thereby promoting fusion with", "thereby promoting fusion with late", "promoting fusion with late endosomes", "fusion with late endosomes and", "with late endosomes and lysosomes", "endosomes and lysosomes liang", "and lysosomes liang et", "lysosomes liang et al." ] }, { "record_id": "GLY_000594_1_791", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "163359", "r hsa", "hsa 163359", "r hsa 163359" ] }, { "record_id": "GLY_000594_1_791", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glucagon signaling", "signaling in", "in metabolic", "metabolic regulation", "glucagon signaling in", "signaling in metabolic", "in metabolic regulation", "glucagon signaling in metabolic", "signaling in metabolic regulation", "glucagon signaling in metabolic regulation", 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some", "events and some of", "and some of their downstream", "some of their downstream consequences", "their downstream consequences are", "downstream consequences are illustrated", "consequences are illustrated below", "are illustrated below adapted", "illustrated below adapted from", "below adapted from jiang", "adapted from jiang and zhang", "jiang and zhang 2003", "and zhang 2003 ." ] }, { "record_id": "GLY_000594_1_792", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "163615", "r hsa", "hsa 163615", "r hsa 163615" ] }, { "record_id": "GLY_000594_1_792", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pka activation", "a number", "number of", "of inactive", "inactive tetrameric", "tetrameric pka", "pka holoenzymes", "holoenzymes are", "are produced", "produced by", "by the", "the combination", "combination of", "of homo", "or heterodimers", "heterodimers of", "of the", "the different", 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"fieldtype": "text", "phraselist": [ "ampk inhibits", "inhibits chrebp", "chrebp transcriptional", "transcriptional activation", "activation activity", "ampk inhibits chrebp", "inhibits chrebp transcriptional", "chrebp transcriptional activation", "transcriptional activation activity", "ampk inhibits chrebp transcriptional", "inhibits chrebp transcriptional activation", "chrebp transcriptional activation activity", "ampk inhibits chrebp transcriptional activation", "inhibits chrebp transcriptional activation activity", "amp activated", "activated protein", "protein kinase", "is a", "a sensor", "sensor of", "of cellular", "cellular energy", "energy levels.", "levels. a", "a high", "high cellular", "cellular ratio", "ratio of", "of amp:atp", "amp:atp triggers", "triggers the", "the phosphorylation", "phosphorylation and", "and activation", "activation of", "of ampk.", "ampk. activated", "activated ampk", "ampk in", "in turn", "turn phosphorylates", "phosphorylates a", "a wide", "wide array", "array of", "of target", "target proteins", "as shown", "shown in", "in the", "the figure", "figure below", "reproduced from", "hardie et", "et al.", "al. 2003", "with the", "the permission", "permission of", "of d.g.", "d.g. hardie", "hardie .", ". these", "these targets", "targets include", "include chrebp", "carbohydrate response", "response element", "element binding", "binding protein", "whose inactivation", "inactivation by", "by phosphorylation", "phosphorylation reduces", "reduces transcription", "transcription of", "of key", "key enzymes", "enzymes of", "of the", "the glycolytic", "glycolytic and", "and lipogenic", "lipogenic pathways.", "amp activated protein", "activated protein kinase", "kinase ampk", "ampk is", "is a sensor", "a sensor of", "sensor of cellular", "of cellular energy", "cellular energy levels.", "energy levels. a", "levels. a high", "a high cellular", "high cellular ratio", "cellular ratio of", "ratio of amp:atp", "of amp:atp triggers", "amp:atp 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array of target", "array of target proteins", "target proteins as", "proteins as shown", "as shown in the", "shown in the figure", "in the figure below", "figure below reproduced", "below reproduced from", "reproduced from hardie", "from hardie et", "hardie et al. 2003", "2003 with", "with the permission of", "the permission of d.g.", "permission of d.g. hardie", "of d.g. hardie .", "d.g. hardie . these", "hardie . these targets", ". these targets include", "these targets include chrebp", "include chrebp carbohydrate", "chrebp carbohydrate response", "carbohydrate response element binding", "response element binding protein", "protein whose", "whose inactivation by phosphorylation", "inactivation by phosphorylation reduces", "by phosphorylation reduces transcription", "phosphorylation reduces transcription of", "reduces transcription of key", "transcription of key enzymes", "of key enzymes of", "key enzymes of the", "enzymes of the glycolytic", "of the glycolytic and", "the glycolytic and lipogenic", "glycolytic and lipogenic pathways.", "activated protein kinase ampk", "kinase ampk is", "ampk is a sensor", "is a sensor of cellular", "a sensor of cellular energy", "sensor of cellular energy levels.", "of cellular energy levels. a", "cellular energy levels. a high", "energy levels. a high cellular", "levels. a high cellular ratio", "a high cellular ratio of", "high cellular ratio of amp:atp", "cellular ratio of amp:atp triggers", "ratio of amp:atp triggers the", "of amp:atp triggers the phosphorylation", "amp:atp triggers the phosphorylation and", "triggers the phosphorylation and activation", "the phosphorylation and activation of", "phosphorylation and activation of ampk.", "and activation of ampk. activated", "activation of ampk. activated ampk", "of ampk. activated ampk in", "ampk. activated ampk in turn", "activated ampk in turn phosphorylates", "ampk in turn phosphorylates a", "in turn phosphorylates a wide", "turn phosphorylates a wide array", "phosphorylates a wide array of", "a wide array of target", "wide array of target proteins", "of target proteins as", "target proteins as shown", "proteins as shown in", "as shown in the figure", "shown in the figure below", "the figure below reproduced", "figure below reproduced from", "reproduced from hardie et", "from hardie et al.", "al. 2003 with", "2003 with the", "with the permission of d.g.", "the permission of d.g. hardie", "permission of d.g. hardie .", "of d.g. hardie . these", "d.g. hardie . these targets", "hardie . these targets include", ". these targets include chrebp", "targets include chrebp carbohydrate", "include chrebp carbohydrate response", "chrebp carbohydrate response element", "carbohydrate response element binding protein", "binding protein whose", "protein whose inactivation", "whose inactivation by phosphorylation reduces", "inactivation by phosphorylation reduces transcription", "by phosphorylation reduces transcription of", "phosphorylation reduces transcription of key", "reduces transcription of key enzymes", "transcription of key enzymes of", "of key enzymes of the", "key enzymes of the glycolytic", "enzymes of the glycolytic and", "of the glycolytic and lipogenic", "the glycolytic and lipogenic pathways." ] }, { "record_id": "GLY_000594_1_794", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "163841", "r hsa", "hsa 163841", "r hsa 163841" ] }, { "record_id": "GLY_000594_1_794", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gamma carboxylation", "and arylsulfatase", "arylsulfatase activation", "carboxylation hypusinylation", "hypusinylation hydroxylation", "hydroxylation and", "and arylsulfatase activation", "gamma carboxylation hypusinylation", "hydroxylation and arylsulfatase", "carboxylation hypusinylation hydroxylation", "hypusinylation hydroxylation and", "hydroxylation and arylsulfatase activation", "after translation", "many newly", "newly formed", 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"translation many", "many newly formed", "newly formed proteins", "formed proteins undergo", "proteins undergo further", "undergo further covalent", "further covalent modifications", "covalent modifications that", "modifications that alter", "that alter their", "alter their functional", "their functional properties", "functional properties and", "properties and that", "and that are", "that are essentially", "are essentially irreversible", "essentially irreversible under", "irreversible under physiological", "under physiological conditions", "physiological conditions in", "conditions in the", "in the body.", "the body. these", "body. these modifications", "these modifications include", "modifications include the", "include the vitamin", "the vitamin k", "vitamin k dependent", "k dependent attachment", "dependent attachment of", "attachment of carboxyl", "of carboxyl groups", "carboxyl groups to", "groups to glutamate", "to glutamate residues", "glutamate residues and", "residues and 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that are essentially", "that are essentially irreversible", "are essentially irreversible under", "essentially irreversible under physiological", "irreversible under physiological conditions", "under physiological conditions in", "physiological conditions in the", "conditions in the body.", "in the body. these", "the body. these modifications", "body. these modifications include", "these modifications include the", "modifications include the vitamin", "include the vitamin k", "the vitamin k dependent", "vitamin k dependent attachment", "k dependent attachment of", "dependent attachment of carboxyl", "attachment of carboxyl groups", "of carboxyl groups to", "carboxyl groups to glutamate", "groups to glutamate residues", "to glutamate residues and", "glutamate residues and the", "residues and the conversion", "and the conversion of", "the conversion of a", "conversion of a lysine", "of a lysine residue", "a lysine residue in", "lysine residue in eif5a", "residue in eif5a to", "in eif5a 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that are", "properties and that are essentially", "and that are essentially irreversible", "that are essentially irreversible under", "are essentially irreversible under physiological", "essentially irreversible under physiological conditions", "irreversible under physiological conditions in", "under physiological conditions in the", "physiological conditions in the body.", "conditions in the body. these", "in the body. these modifications", "the body. these modifications include", "body. these modifications include the", "these modifications include the vitamin", "modifications include the vitamin k", "include the vitamin k dependent", "the vitamin k dependent attachment", "vitamin k dependent attachment of", "k dependent attachment of carboxyl", "dependent attachment of carboxyl groups", "attachment of carboxyl groups to", "of carboxyl groups to glutamate", "carboxyl groups to glutamate residues", "groups to glutamate residues and", "to glutamate residues and the", "glutamate residues and the conversion", "residues and the conversion of", "and the conversion of a", "the conversion of a lysine", "conversion of a lysine residue", "of a lysine residue in", "a lysine residue in eif5a", "lysine residue in eif5a to", "residue in eif5a to hypusine", "eif5a to hypusine the", "to hypusine the conversion", "hypusine the conversion of", "the conversion of a histidine", "conversion of a histidine residue", "of a histidine residue in", "a histidine residue in eef", "histidine residue in eef to", "residue in eef to diphthamide", "eef to diphthamide and", "to diphthamide and the", "diphthamide and the hydrxylation", "and the hydrxylation of various", "the hydrxylation of various amino", "hydrxylation of various amino acid", "of various amino acid side", "various amino acid side chains." ] }, { "record_id": "GLY_000594_1_795", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "164378", "r hsa", "hsa 164378", "r hsa 164378" ] }, { "record_id": "GLY_000594_1_795", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pka activation", "activation in", "in glucagon", "glucagon signalling", "pka activation in", "activation in glucagon", "in glucagon signalling", "pka activation in glucagon", "activation in glucagon signalling", "pka activation in glucagon signalling", "adenylate cyclase", "cyclase catalyses", "catalyses the", "the synthesis", "synthesis of", "of cyclic", "cyclic amp", "from atp.", "atp. in", "in the", "the absence", "absence of", "of camp", "protein kinase", "kinase a", "exists as", "as inactive", "inactive tetramers", "tetramers of", "of two", "two catalytic", "catalytic subunits", "subunits and", "and two", "two regulatory", "regulatory subunits.", "subunits. camp", "camp binding", "binding to", "to pka", "pka tetramers", "tetramers causes", "causes them", "them to", "to dissociate", "dissociate and", "and release", "release their", "their catalytic", 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disease", "metabolic disease and", "disease and diabetes", "and diabetes laplante", "diabetes laplante &", "laplante & sabatini 2012", "& sabatini 2012 .", "sabatini 2012 . in", "2012 . in cells", "in cells mtor", "cells mtor exists", "mtor exists as two", "exists as two structurally", "as two structurally distinct", "two structurally distinct complexes", "structurally distinct complexes termed", "distinct complexes termed mtor", "complexes termed mtor complex", "termed mtor complex 1", "complex 1 mtorc1", "mtorc1 and mtor", "and mtor complex 2", "complex 2 mtorc2", "mtorc2 each", "each one with specificity", "one with specificity for", "with specificity for different", "specificity for different sets", "for different sets of", "different sets of effectors.", "sets of effectors. mtorc1", "of effectors. mtorc1 couples", "effectors. mtorc1 couples energy", "mtorc1 couples energy and", "couples energy and nutrient", "energy and nutrient abundance", "and nutrient abundance to", "nutrient abundance to cell", "abundance to cell growth", "to cell growth and", "cell growth and proliferation", "growth and proliferation by", "and proliferation by balancing", "proliferation by balancing anabolic", "balancing anabolic protein", "anabolic protein synthesis", "protein synthesis and nutrient", "synthesis and nutrient storage", "nutrient storage and", "storage and catabolic", "and catabolic autophagy", "catabolic autophagy and", "autophagy and utilization of", "and utilization of energy", "utilization of energy stores", "energy stores processes.", "target of rapamycin mtor", "rapamycin mtor is", "mtor is a highly", "is a highly conserved serine/threonine", "a highly conserved serine/threonine kinase", "highly conserved serine/threonine kinase that", "conserved serine/threonine kinase that regulates", "serine/threonine kinase that regulates cell", "kinase that regulates cell growth", "that regulates cell growth and", "regulates cell growth and division", "cell growth and division 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cells", ". in cells mtor", "in cells mtor exists", "cells mtor exists as", "mtor exists as two structurally", "exists as two structurally distinct", "as two structurally distinct complexes", "two structurally distinct complexes termed", "structurally distinct complexes termed mtor", "distinct complexes termed mtor complex", "complexes termed mtor complex 1", "mtor complex 1 mtorc1", "1 mtorc1 and", "mtorc1 and mtor complex", "mtor complex 2 mtorc2", "mtorc2 each one", "each one with specificity for", "one with specificity for different", "with specificity for different sets", "specificity for different sets of", "for different sets of effectors.", "different sets of effectors. mtorc1", "sets of effectors. mtorc1 couples", "of effectors. mtorc1 couples energy", "effectors. mtorc1 couples energy and", "mtorc1 couples energy and nutrient", "couples energy and nutrient abundance", "energy and nutrient abundance to", "and nutrient abundance to cell", "nutrient abundance to cell growth", 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a", "at this time unclear.

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a benefit for the", "unclear.

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membrane", "membrane resulting", "resulting in net", "in net proton", "net proton transport", "proton transport catalysed", "transport catalysed by", "catalysed by the", "by the protein.", "the \\fatty acid cycling\\", "\\fatty acid cycling\\ hypothesis", "acid cycling\\ hypothesis proposes", "cycling\\ hypothesis proposes that", "hypothesis proposes that protonated", "proposes that protonated fatty", "that protonated fatty acids", "protonated fatty acids flip", "fatty acids flip flop", "acids flip flop in", "flip flop in the", "flop in the membrane", "in the membrane and", "the membrane and deliver", "membrane and deliver a", "and deliver a proton", "deliver a proton to", "a proton to the", "proton to the matrix", "to the matrix side.", "the matrix side. ucp1", "matrix side. ucp1 catalyses", "side. ucp1 catalyses the", "ucp1 catalyses the return", "catalyses the return of", "the return of the", "return of the fatty", "of the fatty acid", "the fatty acid anion", "fatty acid anion to", 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"pathogen associated molecular patterns", "molecular patterns pamps", "pamps flagellin", "flagellin does not undergo", "does not undergo any", "not undergo any posttranslational", "undergo any posttranslational modifications", "any posttranslational modifications that", "posttranslational modifications that would", "modifications that would distinguish", "that would distinguish it", "would distinguish it from", "distinguish it from cellular", "it from cellular proteins.", "from cellular proteins. however", "proteins. however flagellin", "however flagellin is", "flagellin is extremely conserved", "is extremely conserved at", "extremely conserved at its", "conserved at its amino", "its amino and", "amino and carboxyl", "carboxyl termini which", "termini which presumably", "which presumably explains why", "presumably explains why it", "explains why it was", "why it was selected", "it was selected as", "was selected as a", "selected as a ligand", "as a ligand for", "a ligand for innate", "ligand for innate immune", "for innate immune recognition.", "innate immune recognition. tlr5", "immune recognition. tlr5 is", "recognition. tlr5 is expressed", "tlr5 is expressed on", "is expressed on epithelial", "expressed on epithelial cells", "on epithelial cells as", "epithelial cells as well", "cells as well as", "as well as on", "well as on macrophages", "as on macrophages and", "on macrophages and dendritic", "macrophages and dendritic cells.", "and dendritic cells. expression", "dendritic cells. expression of", "cells. expression of tlr5", "expression of tlr5 on", "of tlr5 on intestinal", "tlr5 on intestinal epithelium", "on intestinal epithelium is", "intestinal epithelium is polarized", "epithelium is polarized such", "is polarized such that", "polarized such that tlr5", "such that tlr5 is", "that tlr5 is expressed", "tlr5 is expressed only", "is expressed only on", "expressed only on the", "only on the basolateral", "on the basolateral side", "the basolateral side of", "basolateral side of the", "side of the cell", "the cell as", "cell as pathogenic", "as pathogenic but not", "pathogenic but not commensal", "but not commensal microbes", "not commensal microbes cross", "commensal microbes cross the", "microbes cross the epithelial", "cross the epithelial barrier.", "the epithelial barrier. this", "epithelial barrier. this ensures", "barrier. this ensures that", "this ensures that innate", "ensures that innate immune", "that innate immune responses", "innate immune responses are", "immune responses are confined", "responses are confined to", "are confined to pathogenic", "confined to pathogenic but", "to pathogenic but not", "commensal microbes paul", "microbes paul 2004", "paul 2004 hayashi", "2004 hayashi et", "hayashi et al. 2001", "al. 2001 gewirtz", "2001 gewirtz et", "gewirtz et al. 2001", "et al. 2001 .", "tlr5 is the receptor for", "is the receptor for flagellin", "receptor for flagellin the", "for flagellin the protein", "flagellin the protein that", "the protein that forms bacterial", "protein that forms bacterial flagella.", "that forms bacterial flagella. unlike", "forms bacterial flagella. unlike most", "bacterial flagella. unlike most other", "flagella. unlike most other pathogen", "unlike most other pathogen associated", "most other pathogen associated molecular", "other pathogen associated molecular patterns", "associated molecular patterns pamps", "pamps flagellin does", "flagellin does not undergo any", "does not undergo any posttranslational", "not undergo any posttranslational modifications", "undergo any posttranslational modifications that", "any posttranslational modifications that would", "posttranslational modifications that would distinguish", "modifications that would distinguish it", "that would distinguish it from", "would distinguish it from cellular", "distinguish it from cellular proteins.", "it from cellular proteins. however", "cellular proteins. however flagellin", "proteins. however flagellin is", "however flagellin is extremely", "flagellin is extremely conserved at", "is extremely conserved at its", "extremely conserved at its amino", "at its amino and", "its amino and carboxyl", "amino and carboxyl termini", "and carboxyl termini which", "carboxyl termini which presumably", "termini which presumably explains", "which presumably explains why it", "presumably explains why it was", "explains why it was selected", "why it was selected as", "it was selected as a", "was selected as a ligand", "selected as a ligand for", "as a ligand for innate", "a ligand for innate immune", "ligand for innate immune recognition.", "for innate immune recognition. tlr5", "innate immune recognition. tlr5 is", "immune recognition. tlr5 is expressed", "recognition. tlr5 is expressed on", "tlr5 is expressed on epithelial", "is expressed on epithelial cells", "expressed on epithelial cells as", "on epithelial cells as well", "epithelial cells as well as", "cells as well as on", "as well as on macrophages", "well as on macrophages and", "as on macrophages and dendritic", "on macrophages and dendritic cells.", "macrophages and dendritic cells. expression", "and dendritic cells. expression of", "dendritic cells. expression of tlr5", "cells. expression of tlr5 on", "expression of tlr5 on intestinal", "of tlr5 on intestinal epithelium", "tlr5 on intestinal epithelium is", "on intestinal epithelium is polarized", "intestinal epithelium is polarized such", "epithelium is polarized such that", "is polarized such that tlr5", "polarized such that tlr5 is", "such that tlr5 is expressed", "that tlr5 is expressed only", "tlr5 is expressed only on", "is expressed only on the", "expressed only on the basolateral", "only on the basolateral side", "on the basolateral side of", "the basolateral side of the", "basolateral side of the cell", "of the cell as", "the cell as pathogenic", "cell as pathogenic but", "as pathogenic but not commensal", "pathogenic but not commensal microbes", "but not commensal microbes cross", "not commensal microbes cross the", "commensal microbes cross the epithelial", "microbes cross the epithelial barrier.", "cross the epithelial barrier. this", "the epithelial barrier. this ensures", "epithelial barrier. this ensures that", "barrier. this ensures that innate", "this ensures that innate immune", "ensures that innate immune responses", "that innate immune responses are", "innate immune responses are confined", "immune responses are confined to", "responses are confined to pathogenic", "are confined to pathogenic but", "confined to pathogenic but not", "to pathogenic but not commensal", "not commensal microbes paul", "commensal microbes paul 2004", "paul 2004 hayashi et", "2004 hayashi et al.", "et al. 2001 gewirtz", "al. 2001 gewirtz et", "2001 gewirtz et al.", "gewirtz et al. 2001 ." ] }, { "record_id": "GLY_000594_1_807", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "168179", "r hsa", "hsa 168179", "r hsa 168179" ] }, { "record_id": "GLY_000594_1_807", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "toll like", "like receptor", "receptor tlr1:tlr2", "tlr1:tlr2 cascade", "toll like receptor", "like receptor tlr1:tlr2", "receptor tlr1:tlr2 cascade", "toll like receptor tlr1:tlr2", "like receptor tlr1:tlr2 cascade", "toll like receptor tlr1:tlr2 cascade", "tlr1 is", "is expressed", "expressed by", "by monocytes.", "monocytes. tlr1", "tlr1 and", "and tlr2", "tlr2 cotranslationally", "cotranslationally form", "form heterodimeric", "heterodimeric complexes", "complexes on", "on the", "the cell", "cell surface", "surface and", "and in", "in the", "the cytosol.", "cytosol. the", "the tlr2:tlr1", "tlr2:tlr1 complex", "complex recognizes", "recognizes neisserial", "neisserial porb", "porb and", "and mycobacterial", "mycobacterial triacylated", "triacylated lipoproteins", "lipoproteins and", "and peptides", "amongst others", "triggering 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cytosol. the", "cytosol. the tlr2:tlr1", "the tlr2:tlr1 complex", "tlr2:tlr1 complex recognizes", "complex recognizes neisserial", "recognizes neisserial porb", "neisserial porb and", "porb and mycobacterial", "and mycobacterial triacylated", "mycobacterial triacylated lipoproteins", "triacylated lipoproteins and", "lipoproteins and peptides", "peptides amongst", "others triggering", "triggering up regulation", "up regulation of", "regulation of nuclear", "of nuclear factor", "nuclear factor kappab", "factor kappab production", "kappab production and", "production and apoptotic", "and apoptotic cascades.", "apoptotic cascades. such", "cascades. such cooperation", "such cooperation between", "cooperation between tlr1", "between tlr1 and", "and tlr2 on", "tlr2 on the", "cell surface of", "surface of normal", "of normal human", "normal human peripheral", "human peripheral blood", "peripheral blood mononuclear", "blood mononuclear cells", "cells for", "instance leads", "leads to the", "to the activation", "the activation of", "activation of pro", "of pro inflammatory", "pro inflammatory cytokine", "inflammatory cytokine secretion", "secretion sandor", "sandor et al.", "et al. 2003", "al. 2003 .", "tlr1 is expressed by", "is expressed by monocytes.", "expressed by monocytes. tlr1", "by monocytes. tlr1 and", "monocytes. tlr1 and tlr2", "tlr1 and tlr2 cotranslationally", "and tlr2 cotranslationally form", "tlr2 cotranslationally form heterodimeric", "cotranslationally form heterodimeric complexes", "form heterodimeric complexes on", "heterodimeric complexes on the", "complexes on the cell", "on the cell surface", "the cell surface and", "cell surface and in", "surface and in the", "and in the cytosol.", "in the cytosol. the", "the cytosol. the tlr2:tlr1", "cytosol. the tlr2:tlr1 complex", "the tlr2:tlr1 complex recognizes", "tlr2:tlr1 complex recognizes neisserial", "complex recognizes neisserial porb", "recognizes neisserial porb and", "neisserial porb and mycobacterial", "porb and mycobacterial triacylated", "and mycobacterial triacylated lipoproteins", "mycobacterial triacylated lipoproteins and", "triacylated lipoproteins and peptides", "and peptides amongst", "peptides amongst others", "amongst others triggering", "others triggering up", "triggering up regulation of", "up regulation of nuclear", "regulation of nuclear factor", "of nuclear factor kappab", "nuclear factor kappab production", "factor kappab production and", "kappab production and apoptotic", "production and apoptotic cascades.", "and apoptotic cascades. such", "apoptotic cascades. such cooperation", "cascades. such cooperation between", "such cooperation between tlr1", "cooperation between tlr1 and", "between tlr1 and tlr2", "tlr1 and tlr2 on", "and tlr2 on the", "tlr2 on the cell", "the cell surface of", "cell surface of normal", "surface of normal human", "of normal human peripheral", "normal human peripheral blood", "human peripheral blood mononuclear", "peripheral blood mononuclear cells", "mononuclear cells for", "cells for instance", "for instance leads", "instance leads to", "leads to the activation", "to the activation of", "the activation of pro", "activation of pro inflammatory", "of pro inflammatory cytokine", "pro inflammatory cytokine secretion", "cytokine secretion sandor", "secretion sandor et", "sandor et al. 2003", "et al. 2003 .", "tlr1 is expressed by monocytes.", "is expressed by monocytes. tlr1", "expressed by monocytes. tlr1 and", "by monocytes. tlr1 and tlr2", "monocytes. tlr1 and tlr2 cotranslationally", "tlr1 and tlr2 cotranslationally form", "and tlr2 cotranslationally form heterodimeric", "tlr2 cotranslationally form heterodimeric complexes", "cotranslationally form heterodimeric complexes on", "form heterodimeric complexes on the", "heterodimeric complexes on the cell", "complexes on the cell surface", "on the cell surface and", "the cell surface and in", "cell surface and in the", "surface and in the cytosol.", "and in the cytosol. the", "in the cytosol. the tlr2:tlr1", "the cytosol. the tlr2:tlr1 complex", "cytosol. the tlr2:tlr1 complex recognizes", "the tlr2:tlr1 complex recognizes neisserial", "tlr2:tlr1 complex recognizes neisserial porb", "complex recognizes neisserial porb and", "recognizes neisserial porb and mycobacterial", "neisserial porb and mycobacterial triacylated", "porb and mycobacterial triacylated lipoproteins", "and mycobacterial triacylated lipoproteins and", "mycobacterial triacylated lipoproteins and peptides", "lipoproteins and peptides amongst", "and peptides amongst others", "amongst others triggering up", "others triggering up regulation", "triggering up regulation of nuclear", "up regulation of nuclear factor", "regulation of nuclear factor kappab", "of nuclear factor kappab production", "nuclear factor kappab production and", "factor kappab production and apoptotic", "kappab production and apoptotic cascades.", "production and apoptotic cascades. such", "and apoptotic cascades. such cooperation", "apoptotic cascades. such cooperation between", "cascades. such cooperation between tlr1", "such cooperation between tlr1 and", "cooperation between tlr1 and tlr2", "between tlr1 and tlr2 on", "tlr1 and tlr2 on the", "and tlr2 on the cell", "tlr2 on the cell surface", "on the cell surface of", "the cell surface of normal", "cell surface of normal human", "surface of normal human peripheral", "of normal human peripheral blood", "normal human peripheral blood mononuclear", "human peripheral blood mononuclear cells", "blood mononuclear cells for", "mononuclear cells for instance", "for instance leads to", "instance leads to the", "leads to the activation of", "to the activation of pro", "the activation of pro inflammatory", "activation of pro inflammatory cytokine", "of pro inflammatory cytokine secretion", "inflammatory cytokine secretion sandor", "cytokine secretion sandor et", "secretion sandor et al.", "sandor et al. 2003 ." ] }, { "record_id": "GLY_000594_1_808", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "168188", "r hsa", "hsa 168188", "r hsa 168188" ] }, { "record_id": "GLY_000594_1_808", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "toll like", "like receptor", "receptor tlr6:tlr2", "tlr6:tlr2 cascade", "toll like receptor", "like receptor tlr6:tlr2", "receptor tlr6:tlr2 cascade", "toll like receptor tlr6:tlr2", "like receptor tlr6:tlr2 cascade", "toll like receptor tlr6:tlr2 cascade", "tlr2 and", "and tlr4", "tlr4 recognize", "recognize different", "different bacterial", "bacterial cell", "cell wall", "wall components.", "components. while", "while tlr4", "tlr4 is", "is trained", "trained onto", "onto gram", "gram negative", "negative lipopolysaccharide", "lipopolysaccharide components", "in combination", "combination with", "with tlr6", "plays a", "a major", "major role", "role in", "in recognizing", "recognizing peptidoglycan", 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telomeric dna can", "be involved.

telomeric dna can form", "involved.

telomeric dna can form higher", "dna can form higher order", "can form higher order structures.", "form higher order structures. electron", "higher order structures. electron microscopy", "order structures. electron microscopy of", "structures. electron microscopy of telomeric", "electron microscopy of telomeric dna", "microscopy of telomeric dna isolated", "of telomeric dna isolated from", "telomeric dna isolated from human", "dna isolated from human cells", "isolated from human cells provided", "from human cells provided evidence", "human cells provided evidence for", "cells provided evidence for lariat", "provided evidence for lariat type", "evidence for lariat type structures", "for lariat type structures termed", "lariat type structures termed telomeric", "type structures termed telomeric loops", "termed telomeric loops or", "telomeric loops or t", "loops or t loops", "or t loops griffith", "t loops griffith et", "loops griffith et al.", "griffith et al. 1999", "et al. 1999 .", "al. 1999 . t", "1999 . t loops are", ". t loops are proposed", "t loops are proposed to", "loops are proposed to result", "are proposed to result from", "proposed to result from the", "to result from the invasion", "result from the invasion of", "from the invasion of the", "the invasion of the 3'", "invasion of the 3' g", "of the 3' g rich", "the 3' g rich single", "3' g rich single strand", "g rich single strand overhang", "rich single strand overhang into", "single strand overhang into the", "strand overhang into the double", "overhang into the double stranded", "into the double stranded telomeric", "the double stranded telomeric ttaggg", "double stranded telomeric ttaggg repeat", "stranded telomeric ttaggg repeat tract.", "telomeric ttaggg repeat tract. the", "ttaggg repeat tract. the function", "repeat tract. the function of", "tract. the function of the", "the function of the t", "function of the t loop", "of the t loop is", "the t loop is presumed", "t loop is presumed to", "loop is presumed to be", "is presumed to be the", "presumed to be the masking", "to be the masking of", "be the masking of the", "the masking of the 3'", "masking of the 3' telomeric", "of the 3' telomeric overhang.", "the 3' telomeric overhang. multiple", "3' telomeric overhang. multiple protein", "telomeric overhang. multiple protein factors", "overhang. multiple protein factors can", "multiple protein factors can bind", "protein factors can bind telomeric", "factors can bind telomeric dna", "can bind telomeric dna and", "bind telomeric dna and likely", "telomeric dna and likely contribute", "dna and likely contribute to", "and likely contribute to dynamic", "contribute to dynamic higher", "to dynamic higher order", "dynamic higher order structures." ] }, { "record_id": "GLY_000594_1_816", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "173107", "r hsa", "hsa 173107", "r hsa 173107" ] }, { "record_id": "GLY_000594_1_816", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "binding and", "and entry", "entry of", "of hiv", "hiv virion", "binding and entry", "and entry of", "entry of hiv", "of hiv virion", "binding and entry of", "and entry of hiv", "entry of hiv virion", "binding and entry of hiv", "and entry of hiv virion", "hiv enters", "enters cells", "cells by", "by fusion", "fusion at", "at the", "the cell", "cell surface", "that results", "results in", "in a", "a productive", "productive infection.", "infection. the", "the envelope", "protein of", "hiv mediates", "mediates entry.", "entry. env", "env is", "is composed", "composed of", "of a", "surface subunit", "and a", "a transmembrane", "transmembrane subunit", "which assemble", "assemble as", "as heterotrimers", "heterotrimers on", "on the", "the virion", "virion surface.the", "surface.the trimeric", "surface gp120", "gp120 protein", "virion engages", "engages cd4", "cd4 on", "the host", "host cell", "inducing conformational", "conformational changes", "changes that", "that promote", "promote binding", "binding to", "to select", "select chemokine", "chemokine receptors", "receptors ccr5", "ccr5 and", "and cxcr4.
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", "hiv enters cells by", "enters cells by fusion", "cells by fusion at", "by fusion at the", "fusion at the cell", "at the cell surface", "cell surface that", "surface that results", "that results in a", "results in a productive", "in a productive infection.", "a productive infection. the", "productive infection. the envelope", "the envelope env", "env protein of", "protein of hiv mediates", "of hiv mediates entry.", "hiv mediates entry. env", "mediates entry. env is", "entry. env is composed", "env is composed of", "is composed of a", "of a surface", "a surface subunit", "surface subunit gp120", "gp120 and a", "and a transmembrane subunit", "transmembrane subunit gp41", "gp41 which assemble", "which assemble as heterotrimers", "assemble as heterotrimers on", "as heterotrimers on the", "heterotrimers on the virion", "on the virion surface.the", "the virion surface.the trimeric", "surface.the trimeric surface", "trimeric surface gp120", "gp120 protein su", "su on the", "on the virion engages", "the virion engages cd4", "virion engages cd4 on", "engages cd4 on the", "cd4 on the host", "on the host cell", "host cell inducing", "cell inducing conformational", "inducing conformational changes that", "conformational changes that promote", "changes that promote binding", "that promote binding to", "promote binding to select", "binding to select chemokine", "to select chemokine receptors", "select chemokine receptors ccr5", "chemokine receptors ccr5 and", "receptors ccr5 and cxcr4.
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", "hiv enters cells by fusion", "enters cells by fusion at", "cells by fusion at the", "by fusion at the cell", "fusion at the cell surface", "the cell surface that", "cell surface that results", "surface that results in", "that results in a productive", "results in a productive infection.", "in a productive infection. the", "a productive infection. the envelope", "infection. the envelope env", "envelope env protein", "env protein of hiv", "protein of hiv mediates entry.", "of hiv mediates entry. env", "hiv mediates entry. env is", "mediates entry. env is composed", "entry. env is composed of", "env is composed of a", "composed of a surface", "of a surface subunit", "subunit gp120 and", "gp120 and a transmembrane", "a transmembrane subunit gp41", "subunit gp41 which", "gp41 which assemble as", "which assemble as heterotrimers on", "assemble as heterotrimers on the", "as heterotrimers on the virion", "heterotrimers on the virion surface.the", "on the virion surface.the trimeric", "virion surface.the trimeric surface", "surface.the trimeric surface gp120", "trimeric surface gp120 protein", "surface gp120 protein su", "protein su on", "su on the virion", "on the virion engages cd4", "the virion engages cd4 on", "virion engages cd4 on the", "engages cd4 on the host", "cd4 on the host cell", "the host cell inducing", "host cell inducing conformational", "cell inducing conformational changes", "inducing conformational changes that promote", "conformational changes that promote binding", "changes that promote binding to", "that promote binding to select", "promote binding to select chemokine", "binding to select chemokine receptors", "to select chemokine receptors ccr5", "select chemokine receptors ccr5 and", "chemokine receptors ccr5 and cxcr4.
the", "receptors ccr5 and cxcr4.
the sequential", "ccr5 and cxcr4.
the sequential interplay", "and cxcr4.
the sequential interplay between", "cxcr4.
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" ] }, { "record_id": "GLY_000594_1_817", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "173599", "r hsa", "hsa 173599", "r hsa 173599" ] }, { "record_id": "GLY_000594_1_817", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of the", "the active", "active cofactor", "udp glucuronate", "formation of the", "of the active", "the active cofactor", "cofactor udp", "formation of the active", "of the active cofactor", "active cofactor udp", "cofactor udp glucuronate", "formation of the active cofactor", "the active cofactor udp", "active cofactor udp glucuronate", "glucose 1", "1 phosphate", "phosphate and", "and utp", "utp are", "are the", "the precursors", "precursors to", "to udp", "glucuronate formation.", "formation. after", "after oxidation", "oxidation of", "the resultant", "resultant complex", "glucuronate is", "is transported", "transported to", "to the", "the er", "er 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glucuronate is transported", "glucuronate is transported to", "is transported to the", "transported to the er", "to the er lumen.", "glucose 1 phosphate and utp", "1 phosphate and utp are", "phosphate and utp are the", "and utp are the precursors", "utp are the precursors to", "are the precursors to udp", "the precursors to udp glucuronate", "precursors to udp glucuronate formation.", "to udp glucuronate formation. after", "udp glucuronate formation. after oxidation", "glucuronate formation. after oxidation of", "formation. after oxidation of the", "after oxidation of the resultant", "oxidation of the resultant complex", "the resultant complex udp", "resultant complex udp glucuronate", "complex udp glucuronate is", "udp glucuronate is transported to", "glucuronate is transported to the", "is transported to the er", "transported to the er lumen." ] }, { "record_id": "GLY_000594_1_818", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "173736", "r hsa", "hsa 173736", "r hsa 173736" ] }, { "record_id": "GLY_000594_1_818", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "alternative complement", "complement activation", "alternative complement activation", "the proteins", "proteins participating", "participating in", "in alternative", "alternative pathway", "pathway activation", "activation are", "are c3", "and c3b", "the factors", "factors b", "and properdin.", "properdin. in", "in the", "the first", "first place", "activation is", "is a", "a positive", "positive feedback", "feedback mechanism", "mechanism to", "to increase", "increase c3b.", "c3b. when", "when c3b", "c3b binds", "binds covalently", "covalently to", "to sugars", "sugars on", "on a", "a cell", "cell surface", "it can", "can become", "become protected.", "protected. then", "then factor", "factor b", "b binds", "binds to", "to c3b.", "c3b. in", "the presence", "presence of", "of factor", "factor d", "bound factor", "b 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it has been suggested that", "has been suggested that the", "been suggested that the cellular", "suggested that the cellular baf", "that the cellular baf protein", "the cellular baf protein binds", "cellular baf protein binds to", "baf protein binds to viral", "protein binds to viral dna", "binds to viral dna and", "to viral dna and diminishes", "viral dna and diminishes autointegration", "dna and diminishes autointegration by", "and diminishes autointegration by coating", "diminishes autointegration by coating and", "autointegration by coating and condensing", "by coating and condensing the", "coating and condensing the viral", "and condensing the viral dna", "the viral dna thereby", "viral dna thereby making", "dna thereby making it", "thereby making it a less", "making it a less efficient", "it a less efficient integration", "a less efficient integration target.
" ] }, { "record_id": "GLY_000594_1_826", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1799339", "r hsa", "hsa 1799339", "r hsa 1799339" ] }, { "record_id": "GLY_000594_1_826", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "srp dependent", "dependent cotranslational", "cotranslational protein", "protein targeting", "targeting to", "to membrane", "srp dependent cotranslational", "dependent cotranslational protein", "cotranslational protein targeting", "protein targeting to", "targeting to membrane", "srp dependent cotranslational protein", "dependent cotranslational protein targeting", "cotranslational protein targeting to", "protein targeting to membrane", "srp dependent cotranslational protein targeting", "dependent cotranslational protein targeting to", "cotranslational protein targeting to membrane", "the process", "process for", "for translation", "translation of", "of a", "a protein", 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the interaction of this", "the interaction of this complex", "interaction of this complex with", "of this complex with a", "this complex with a cytosolic", "complex with a cytosolic signal", "with a cytosolic signal recognition", "a cytosolic signal recognition particle", "signal recognition particle srp", "particle srp to", "srp to form a", "to form a complex which", "form a complex which in", "a complex which in turn", "complex which in turn docks", "which in turn docks with", "in turn docks with an", "turn docks with an srp", "docks with an srp receptor", "with an srp receptor complex", "an srp receptor complex on", "srp receptor complex on the", "receptor complex on the er", "complex on the er membrane.", "on the er membrane. there", "the er membrane. there the", "er membrane. there the ribosome", "membrane. there the ribosome complex", "there the ribosome complex is", "the ribosome complex is transferred", "ribosome complex is transferred from", "complex is transferred from the", 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lumen. translation which", "lumen. translation which had", "translation which had been", "which had been halted by", "had been halted by srp", "been halted by srp binding", "by srp binding now", "srp binding now resumes", "now resumes the signal", "resumes the signal peptide", "the signal peptide is cleaved", "signal peptide is cleaved from", "peptide is cleaved from the", "is cleaved from the polypeptide", "from the polypeptide and", "the polypeptide and elongation", "polypeptide and elongation proceeds", "and elongation proceeds with", "elongation proceeds with the", "proceeds with the growing", "with the growing polypeptide oriented", "the growing polypeptide oriented into", "growing polypeptide oriented into the", "polypeptide oriented into the er", "oriented into the er lumen." ] }, { "record_id": "GLY_000594_1_827", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "180689", "r hsa", "hsa 180689", "r hsa 180689" ] }, { "record_id": "GLY_000594_1_827", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "apobec3g mediated", "mediated resistance", "resistance to", "to hiv", "hiv 1", "1 infection", "apobec3g mediated resistance", "mediated resistance to", "resistance to hiv", "to hiv 1", "hiv 1 infection", "apobec3g mediated resistance to", "mediated resistance to hiv", "resistance to hiv 1", "to hiv 1 infection", "apobec3g mediated resistance to hiv", "mediated resistance to hiv 1", "resistance to hiv 1 infection", "representatives of", "of the", "the apolipoprotein", "apolipoprotein b", "b mrna", "mrna editing", "editing enzyme", "enzyme catalytic", "catalytic polypeptide", "polypeptide 3", "family provide", "provide innate", "innate resistance", "to exogeneous", "exogeneous and", "and endogenous", "endogenous retroviruses", "see cullen", "cullen 2006", "2006 for", "for a", "a recent", "recent review", "review .", "humans and", "and other", "other primates", "primates encode", "encode a", "a cluster", "cluster of", "of seven", "seven different", "different cytidine", "cytidine deaminases", "deaminases with", "with apobec3g", "apobec3f and", "and apobec3b", "apobec3b having", "having some", "some anti", "anti hiv", "1 activity.", "activity. our", "our understanding", "understanding is", "is most", "most complete", "complete for", "for apobec3g", "apobec3g which", "which has", "has been", "been described", "described first", "first and", "and the", "the reactions", "reactions described", "described herein", "herein will", "will focus", "focus on", "on this", "this representative", "representative enzyme.

apobec3g", "enzyme.

apobec3g is", "is a", "a cytoplasmic", "cytoplasmic protein", "protein which", "which strongly", "strongly restricts", "restricts replication", "replication of", "of vif", "vif deficient", "deficient hiv", "sheehy 2002", "2002 .", ". it", "it is", "is expressed", "expressed in", "in cell", "cell populations", "populations that", "that are", "are susceptible", "susceptible to", "hiv infection", "t lymphocytes", "lymphocytes and", "and macrophages", "macrophages .", "in the", "the producer", "producer cell", "apobec3g is", "is incorporated", "incorporated into", "into budding", "budding hiv", "1 particles", "particles through", "through an", "an interaction", "interaction with", "with hiv", "1 gag", "gag nucleocapsid", "protein in", "in a", "a rna", "rna dependent", "dependent fashion.", "fashion.

within", "

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apobec3g", "representative enzyme.

apobec3g is", "enzyme.

apobec3g is a", "is a cytoplasmic", "a cytoplasmic protein", "cytoplasmic protein which", "protein which strongly", "which strongly restricts", "strongly restricts replication", "restricts replication of", "replication of vif", "of vif deficient", "vif deficient hiv", "deficient hiv 1", "1 sheehy", "sheehy 2002 .", "2002 . it", ". it is", "it is expressed", "is expressed in", "expressed in cell", "in cell populations", "cell populations that", "populations that are", "that are susceptible", "are susceptible to", "susceptible to hiv", "to hiv infection", "infection e.g.", "e.g. t", "t lymphocytes and", "lymphocytes and macrophages", "and macrophages .", ". in", "in the producer", "the producer cell", "cell apobec3g", "apobec3g is incorporated", "is incorporated into", "incorporated into budding", "into budding hiv", "budding hiv 1", "hiv 1 particles", "1 particles through", "particles through an", "through an interaction", "an interaction with", "interaction with hiv", "with hiv 1", "hiv 1 gag", "1 gag nucleocapsid", "nucleocapsid nc", "nc protein", "protein in a", "in a rna", "a rna dependent", "rna dependent fashion.", "dependent fashion.

within", "fashion.

within the", "

within the newly", "the newly infected", "newly infected cell", "cell =", "= target cell", "virus associated apobec3g", "associated apobec3g regulates", "apobec3g regulates the", "regulates the infectivity", "the infectivity of", "infectivity of hiv", "of hiv 1", "hiv 1 by", "1 by deaminating", "by deaminating cytidine", "deaminating cytidine to", "cytidine to uracil", "to uracil in", "uracil in the", "in the minus", "the minus strand", "minus strand viral", "strand viral dna", "viral dna intermediate", "dna intermediate during", "intermediate during reverse", "during reverse transcription.", "reverse transcription. deamination", "transcription. deamination results", "deamination results in", "results in the", "in the induction", "the induction of", "induction of g", "of g to", "g to a", "to a hypermutations", "a hypermutations in", "hypermutations in the", "in the plus", "the plus strand", "plus strand viral", "viral dna which", "dna which subsequently", "which subsequently can", "subsequently can either", "can either be", "either be integrated", "be integrated as", "integrated as a", "as a non", "a non functional", "non functional provirus", "functional provirus or", "provirus or degraded", "or degraded before", "degraded before integration.", "representatives of the apolipoprotein", "of the apolipoprotein b", "the apolipoprotein b mrna", "apolipoprotein b mrna editing", "b mrna editing enzyme", "mrna editing enzyme catalytic", "editing enzyme catalytic polypeptide", "enzyme catalytic polypeptide 3", "polypeptide 3 apobec3", "apobec3 family provide", "family provide innate resistance", "provide innate resistance to", "innate resistance to exogeneous", "resistance to exogeneous and", "to exogeneous and endogenous", "exogeneous and endogenous retroviruses", "endogenous retroviruses see", "retroviruses see cullen", "see cullen 2006 for", "cullen 2006 for a", "2006 for a recent", "for a recent review", "a recent review .", "review . humans", ". humans and", "humans and other primates", "and other primates encode", "other primates encode a", "primates encode a cluster", "encode a cluster of", "a cluster of seven", "cluster of seven different", "of seven different cytidine", "seven different cytidine deaminases", "different cytidine deaminases with", "cytidine deaminases with apobec3g", "with apobec3g apobec3f", "apobec3g apobec3f and", "apobec3f and apobec3b having", "and apobec3b having some", "apobec3b having some anti", "having some anti hiv", "some anti hiv 1", "anti hiv 1 activity.", "hiv 1 activity. our", "1 activity. our understanding", "activity. our understanding is", "our understanding is most", "understanding is most complete", "is most complete for", "most complete for apobec3g", "complete for apobec3g which", "for apobec3g which has", "apobec3g which has been", "which has been described", "has been described first", "been described first and", "described first and the", "first and the reactions", "and the reactions described", "the reactions described herein", "reactions described herein will", "described herein will focus", "herein will focus on", "will focus on this", "focus on this representative", "on this representative enzyme.

apobec3g", "this representative enzyme.

apobec3g is", "representative enzyme.

apobec3g is a", "enzyme.

apobec3g is a cytoplasmic", "is a cytoplasmic protein", "a cytoplasmic protein which", "cytoplasmic protein which strongly", "protein which strongly restricts", "which strongly restricts replication", "strongly restricts replication of", "restricts replication of vif", "replication of vif deficient", "of vif deficient hiv", "vif deficient hiv 1", "hiv 1 sheehy", "1 sheehy 2002", "sheehy 2002 . it", "2002 . it is", ". it is expressed", "it is expressed in", "is expressed in cell", "expressed in cell populations", "in cell populations that", "cell populations that are", "populations that are susceptible", "that are susceptible to", "are susceptible to hiv", "susceptible to hiv infection", "hiv infection e.g.", "e.g. t lymphocytes", "t lymphocytes and macrophages", "lymphocytes and macrophages .", "macrophages . in", ". in the", "in the producer cell", "producer cell apobec3g", "cell apobec3g is", "apobec3g is incorporated into", "is incorporated into budding", "incorporated into budding hiv", "into budding hiv 1", "budding hiv 1 particles", "hiv 1 particles through", "1 particles through an", "particles through an interaction", "through an interaction with", "an interaction with hiv", "interaction with hiv 1", "with hiv 1 gag", "hiv 1 gag nucleocapsid", "gag nucleocapsid nc", "nc protein in", "protein in a rna", "in a rna dependent", "a rna dependent fashion.", "rna dependent fashion.

within", "dependent fashion.

within the", "fashion.

within the newly", "

within the newly infected", "the newly infected cell", "infected cell =", "cell = target", "cell virus", "virus associated apobec3g regulates", "associated apobec3g regulates the", "apobec3g regulates the infectivity", "regulates the infectivity of", "the infectivity of hiv", "infectivity of hiv 1", "of hiv 1 by", "hiv 1 by deaminating", "1 by deaminating cytidine", "by deaminating cytidine to", "deaminating cytidine to uracil", "cytidine to uracil in", "to uracil in the", "uracil in the minus", "in the minus strand", "the minus strand viral", "minus strand viral dna", "strand viral dna intermediate", "viral dna intermediate during", "dna intermediate during reverse", "intermediate during reverse transcription.", "during reverse transcription. deamination", "reverse transcription. deamination results", "transcription. deamination results in", "deamination results in the", "results in the induction", "in the induction of", "the induction of g", "induction of g to", "of g to a", "g to a hypermutations", "to a hypermutations in", "a hypermutations in the", "hypermutations in the plus", "in the plus strand", "the plus strand viral", "plus strand viral dna", "strand viral dna which", "viral dna which subsequently", "dna which subsequently can", "which subsequently can either", "subsequently can either be", "can either be integrated", "either be integrated as", "be integrated as a", "integrated as a non", "as a non functional", "a non functional provirus", "non functional provirus or", "functional provirus or degraded", "provirus or degraded before", "or degraded before integration.", "representatives of the apolipoprotein b", "of the apolipoprotein b mrna", "the apolipoprotein b mrna editing", "apolipoprotein b mrna editing enzyme", "b mrna editing enzyme catalytic", "mrna editing enzyme catalytic polypeptide", "editing enzyme catalytic polypeptide 3", "catalytic polypeptide 3 apobec3", "3 apobec3 family", "apobec3 family provide innate", "family provide innate resistance to", "provide innate resistance to exogeneous", "innate resistance to exogeneous and", "resistance to exogeneous and endogenous", "to exogeneous and endogenous retroviruses", "and endogenous retroviruses see", "endogenous retroviruses see cullen", "retroviruses see cullen 2006", "see cullen 2006 for a", "cullen 2006 for a recent", "2006 for a recent review", "for a recent review .", "recent review . humans", "review . humans and", ". humans and other", "humans and other primates encode", "and other primates encode a", "other primates encode a cluster", "primates encode a cluster of", "encode a cluster of seven", "a cluster of seven different", "cluster of seven different cytidine", "of seven different cytidine deaminases", "seven different cytidine deaminases with", "different cytidine deaminases with apobec3g", "deaminases with apobec3g apobec3f", "with apobec3g apobec3f and", "apobec3g apobec3f and apobec3b", "apobec3f and apobec3b having some", "and apobec3b having some anti", "apobec3b having some anti hiv", "having some anti hiv 1", "some anti hiv 1 activity.", "anti hiv 1 activity. our", "hiv 1 activity. our understanding", "1 activity. our understanding is", "activity. our understanding is most", "our understanding is most complete", "understanding is most complete for", "is most complete for apobec3g", "most complete for apobec3g which", "complete for apobec3g which has", "for apobec3g which has been", "apobec3g which has been described", "which has been described first", "has been described first and", "been described first and the", "described first and the reactions", "first and the reactions described", "and the reactions described herein", "the reactions described herein will", "reactions described herein will focus", "described herein will focus on", "herein will focus on this", "will focus on this representative", "focus on this representative enzyme.

apobec3g", "on this representative enzyme.

apobec3g is", "this representative enzyme.

apobec3g is a", "representative enzyme.

apobec3g is a cytoplasmic", "enzyme.

apobec3g is a cytoplasmic protein", "is a cytoplasmic protein which", "a cytoplasmic protein which strongly", "cytoplasmic protein which strongly restricts", "protein which strongly restricts replication", "which strongly restricts replication of", "strongly restricts replication of vif", "restricts replication of vif deficient", "replication of vif deficient hiv", "of vif deficient hiv 1", "deficient hiv 1 sheehy", "hiv 1 sheehy 2002", "1 sheehy 2002 .", "sheehy 2002 . it is", "2002 . it is expressed", ". it is expressed in", "it is expressed in cell", "is expressed in cell populations", "expressed in cell populations that", "in cell populations that are", "cell populations that are susceptible", "populations that are susceptible to", "that are susceptible to hiv", "are susceptible to hiv infection", "to hiv infection e.g.", "infection e.g. t", "e.g. t lymphocytes and", "t lymphocytes and macrophages .", "and macrophages . in", "macrophages . in the", ". in the producer", "the producer cell apobec3g", "producer cell apobec3g is", "cell apobec3g is incorporated", "apobec3g is incorporated into budding", "is incorporated into budding hiv", "incorporated into budding hiv 1", "into budding hiv 1 particles", "budding hiv 1 particles through", "hiv 1 particles through an", "1 particles through an interaction", "particles through an interaction with", "through an interaction with hiv", "an interaction with hiv 1", "interaction with hiv 1 gag", "with hiv 1 gag nucleocapsid", "1 gag nucleocapsid nc", "nucleocapsid nc protein", "nc protein in a", "protein in a rna dependent", "in a rna dependent fashion.", "a rna dependent fashion.

within", "rna dependent fashion.

within the", "dependent fashion.

within the newly", "fashion.

within the newly infected", "

within the newly infected cell", "newly infected cell =", "infected cell = target", "cell = target cell", "target cell virus", "cell virus associated", "virus associated apobec3g regulates the", "associated apobec3g regulates the infectivity", "apobec3g regulates the infectivity of", "regulates the infectivity of hiv", "the infectivity of hiv 1", "infectivity of hiv 1 by", "of hiv 1 by deaminating", "hiv 1 by deaminating cytidine", "1 by deaminating cytidine to", "by deaminating cytidine to uracil", "deaminating cytidine to uracil in", "cytidine to uracil in the", "to uracil in the minus", "uracil in the minus strand", "in the minus strand viral", "the minus strand viral dna", "minus strand viral dna intermediate", "strand viral dna intermediate during", "viral dna intermediate during reverse", "dna intermediate during reverse transcription.", "intermediate during reverse transcription. deamination", "during reverse transcription. deamination results", "reverse transcription. deamination results in", "transcription. deamination results in the", "deamination results in the induction", "results in the induction of", "in the induction of g", "the induction of g to", "induction of g to a", "of g to a hypermutations", "g to a hypermutations in", "to a hypermutations in the", "a hypermutations in the plus", "hypermutations in the plus strand", "in the plus strand viral", "the plus strand viral dna", "plus strand viral dna which", "strand viral dna which subsequently", "viral dna which subsequently can", "dna which subsequently can either", "which subsequently can either be", "subsequently can either be integrated", "can either be integrated as", "either be integrated as a", "be integrated as a non", "integrated as a non functional", "as a non functional provirus", "a non functional provirus or", "non functional provirus or degraded", "functional provirus or degraded before", "provirus or degraded before integration." ] }, { "record_id": "GLY_000594_1_828", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "182218", "r hsa", "hsa 182218", "r hsa 182218" ] }, { "record_id": "GLY_000594_1_828", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nef mediated", "mediated cd8", "cd8 down", "down regulation", "nef mediated cd8", "mediated cd8 down", "cd8 down regulation", "nef mediated cd8 down", "mediated cd8 down regulation", "nef mediated cd8 down regulation", "human immunodeficiency", "immunodeficiency virus", "nef is", "is a", "a membrane", "membrane associated", "associated protein", "protein decreasing", "decreasing surface", "surface expression", "expression of", "of cd4", "and major", "major histocompatibility", "histocompatibility complex", "complex class", "class i", "i on", "on infected", "infected cells.", "cells. nef", "nef also", "also strongly", "strongly down", "down modulates", "modulates surface", "of the", "the beta", "beta chain", "chain 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cytoplasmic tail of the", "cytoplasmic tail of the cd8", "tail of the cd8 beta", "of the cd8 beta chain", "the cd8 beta chain indicates", "cd8 beta chain indicates that", "beta chain indicates that an", "chain indicates that an fmk", "indicates that an fmk amino", "that an fmk amino acid", "an fmk amino acid motif", "fmk amino acid motif is", "amino acid motif is critical", "acid motif is critical for", "motif is critical for the", "is critical for the nef", "critical for the nef induced", "for the nef induced endocytosis.", "the nef induced endocytosis. although", "nef induced endocytosis. although independent", "induced endocytosis. although independent of", "endocytosis. although independent of cd4", "independent of cd4 endocytosis", "of cd4 endocytosis of", "cd4 endocytosis of the", "endocytosis of the cd8 beta", "the cd8 beta chain is", "cd8 beta chain is abrogated", "beta chain is abrogated by", "chain is abrogated by the", "is abrogated by the same", "abrogated by the same 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sivmac239 nef", "immunodeficiency virus sivmac239 nef and", "virus sivmac239 nef and required", "sivmac239 nef and required an", "nef and required an intact", "and required an intact ap", "required an intact ap 2", "an intact ap 2 complex." ] }, { "record_id": "GLY_000594_1_829", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1839130", "r hsa", "hsa 1839130", "r hsa 1839130" ] }, { "record_id": "GLY_000594_1_829", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by activated", "activated point", "point mutants", "mutants of", "of fgfr3", "signaling by activated", "by activated point", "activated point mutants", "point mutants of", "mutants of fgfr3", "signaling by activated point", "by activated point mutants", "activated point mutants of", "point mutants of fgfr3", "signaling by activated point mutants", "by activated point mutants of", "activated point mutants of fgfr3", 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being", "now being identified", "being identified in", "identified in a", "in a range", "a range of", "range of cancers", "of cancers including", "cancers including bladder", "bladder cervical", "cervical breast", "breast prostate", "prostate head", "head and neck", "neck and", "and multiple myeloma", "myeloma reviewed", "reviewed in wesche", "wesche 2011", "activating point mutations in", "point mutations in fgfr3", "mutations in fgfr3 are", "in fgfr3 are found", "fgfr3 are found in", "are found in the", "found in the extracellular", "in the extracellular ligand", "the extracellular ligand binding", "extracellular ligand binding domain", "binding domain the", "domain the transmembrane", "the transmembrane region and", "transmembrane region and the", "region and the tyrosine", "and the tyrosine kinase", "the tyrosine kinase domain", "tyrosine kinase domain and", "kinase domain and are", "domain and are believed", "and are believed to", "are believed to result", "believed to result in", 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"of the receptor webster", "the receptor webster and", "receptor webster and donoghue", "webster and donoghue 1996", "donoghue 1996 wenbster", "1996 wenbster 1997", "1997 . these mutations", "these mutations although initially", "mutations although initially characterized", "although initially characterized in the", "initially characterized in the context", "characterized in the context of", "in the context of autosomal", "the context of autosomal skeletal", "context of autosomal skeletal disorders", "autosomal skeletal disorders are", "skeletal disorders are now", "disorders are now being", "are now being identified in", "now being identified in a", "being identified in a range", "identified in a range of", "in a range of cancers", "a range of cancers including", "range of cancers including bladder", "cancers including bladder cervical", "bladder cervical breast", "cervical breast prostate", "breast prostate head", "prostate head and neck", "head and neck and", "and neck and multiple", "neck and multiple myeloma", "and multiple myeloma reviewed", "multiple myeloma reviewed in", "myeloma reviewed in wesche", "reviewed in wesche 2011", "in wesche 2011 ." ] }, { "record_id": "GLY_000594_1_830", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1855167", "r hsa", "hsa 1855167", "r hsa 1855167" ] }, { "record_id": "GLY_000594_1_830", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pyrophosphates", "pyrophosphates in", "in the", "the cytosol", "synthesis of pyrophosphates", "of pyrophosphates in", "pyrophosphates in the", "in the cytosol", "synthesis of pyrophosphates in", "of pyrophosphates in the", "pyrophosphates in the cytosol", "synthesis of pyrophosphates in the", "of pyrophosphates in the cytosol", "inositol phosphates", "phosphates such", "such as", "as ip4", "ip5 and", "and ip6", "ip6 are", "are converted", "converted to", "to an", "an even", "even wider", "wider variety", "variety of", "of ips", "ips including", "including the", "the di", "and triphospho", "triphospho inositol", "also known", "known as", "as pyrophosphates", "irvine &", "& schell", "schell 2001", "alcazar romain", "romain &", "& wente", "wente 2008", "york 2006", "monserrate and", "and york", "york 2010", "ho et", "et al.", "al. 2002", "saiardi et", "al. 2001", "draskovic et", "al. 2008", "choi et", "al. 2007", "caffrey et", "al. 2000", "leslie et", "2002 .", "inositol phosphates such", "phosphates such as", "such as ip4", "ip4 ip5", "ip5 and ip6", "and ip6 are", "ip6 are converted", "are converted to", "converted to an", "to an even", "an even wider", "even wider variety", "wider variety of", "variety of ips", "of ips including", "ips including the", "including the di", "di and", "and triphospho inositol", "triphospho inositol phosphates", "phosphates also", "also known as", "known as pyrophosphates", "pyrophosphates irvine", "irvine & schell", "& schell 2001", "2001 alcazar", "alcazar romain &", "romain & wente", "& wente 2008", "2008 york", "2006 monserrate", "monserrate and york", "and york 2010", "2010 ho", "ho et al.", "et al. 2002", "2002 saiardi", "saiardi et al.", "et al. 2001", "2001 draskovic", "draskovic et al.", "et al. 2008", "2008 choi", "choi et al.", "et al. 2007", "2007 caffrey", "caffrey et al.", "et al. 2000", "2000 leslie", "leslie et al.", "al. 2002 .", "inositol phosphates such as", "phosphates such as ip4", "as ip4 ip5", "ip4 ip5 and", "ip5 and ip6 are", "and ip6 are converted", "ip6 are converted to", "are converted to an", "converted to an even", "to an even wider", "an even wider variety", "even wider variety of", "wider variety of ips", "variety of ips including", "of ips including the", "ips including the di", "the di and", "di and triphospho", "and triphospho inositol phosphates", "inositol phosphates also", "phosphates also known", "also known as pyrophosphates", "as pyrophosphates irvine", "pyrophosphates irvine &", "irvine & schell 2001", "schell 2001 alcazar", "2001 alcazar romain", "alcazar romain & wente", "romain & wente 2008", "wente 2008 york", "2008 york 2006", "york 2006 monserrate", "2006 monserrate and", "monserrate and york 2010", "york 2010 ho", "2010 ho et", "ho et al. 2002", "al. 2002 saiardi", "2002 saiardi et", "saiardi et al. 2001", "al. 2001 draskovic", "2001 draskovic et", "draskovic et al. 2008", "al. 2008 choi", "2008 choi et", "choi et al. 2007", "al. 2007 caffrey", "2007 caffrey et", "caffrey et al. 2000", "al. 2000 leslie", "2000 leslie et", "leslie et al. 2002", "et al. 2002 .", "inositol phosphates such as ip4", "such as ip4 ip5", "as ip4 ip5 and", "ip4 ip5 and ip6", "ip5 and ip6 are converted", "and ip6 are converted to", "ip6 are converted to an", "are converted to an even", "converted to an even wider", "to an even wider variety", "an even wider variety of", "even wider variety of ips", "wider variety of ips including", "variety of ips including the", "of ips including the di", "including the di and", "the di and triphospho", "di and triphospho inositol", "triphospho inositol phosphates also", "inositol phosphates also known", "phosphates also known as", "known as pyrophosphates irvine", "as pyrophosphates irvine &", "pyrophosphates irvine & schell", "& schell 2001 alcazar", "schell 2001 alcazar romain", "2001 alcazar romain &", "alcazar romain & wente 2008", "& wente 2008 york", "wente 2008 york 2006", "york 2006 monserrate and", "2006 monserrate and york", "and york 2010 ho", "york 2010 ho et", "2010 ho et al.", "et al. 2002 saiardi", "al. 2002 saiardi et", "2002 saiardi et al.", "et al. 2001 draskovic", "al. 2001 draskovic et", "2001 draskovic et al.", "et al. 2008 choi", "al. 2008 choi et", "2008 choi et al.", "et al. 2007 caffrey", "al. 2007 caffrey et", "2007 caffrey et al.", "et al. 2000 leslie", "al. 2000 leslie et", "2000 leslie et al.", "leslie et al. 2002 ." ] }, { "record_id": "GLY_000594_1_831", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "187042", "r hsa", "hsa 187042", "r hsa 187042" ] }, { "record_id": "GLY_000594_1_831", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "trka activation", "activation by", "by ngf", "trka activation by", "activation by ngf", "trka activation by ngf", "neurotrophin functions", "are mediated", "mediated by", "by binding", "binding of", "of the", "the secreted", "secreted neurotrophin", "neurotrophin homodimers", "homodimers to", "to their", "their common", "common neurotrophin", "neurotrophin receptor", "receptor p75ntr", "and to", "their cognate", "cognate tropomyosin", "tropomyosin related", "related kinase", "receptor. ngf", "ngf binds", "binds to", "to trka", "bdnf and", "and nt4", "nt4 bind", "bind to", "to trkb", "nt3 binds", "to trkc.", "trkc. a", "a tri", "tri molecular", "molecular signalling", "signalling complex", "ngf p75ntr", "p75ntr trka", "might 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in", "2002 .

in the", ".

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in the", "2002 .

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bjorkhem et al.", "et al. 1994 babiker", "al. 1994 babiker et", "1994 babiker et al.", "et al. 1999 javitt", "al. 1999 javitt 2002", "1999 javitt 2002 .

in", "javitt 2002 .

in the liver", ".

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transcription", "such as transcription of immediate", "as transcription of immediate early", "transcription of immediate early genes", "immediate early genes proliferation", "early genes proliferation arrest", "proliferation arrest and neurite", "arrest and neurite outgrowth." ] }, { "record_id": "GLY_000594_1_856", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "198753", "r hsa", "hsa 198753", "r hsa 198753" ] }, { "record_id": "GLY_000594_1_856", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "erk/mapk targets", "erk/mapk kinases", "kinases have", "have a", "a number", "number of", "of targets", "targets within", "within the", "the nucleus", "usually transcription", "transcription factors", "factors or", "or other", "other kinases.", "kinases. the", "the best", "best known", "known targets", "rsk1/2/3 and", "and mef2", "mef2 are", "are annotated", "annotated here.", "erk/mapk kinases have", "kinases have a", "have a number", "a number of", "number of targets", "of targets within", "targets within the", "within the nucleus", "nucleus usually", "usually transcription factors", "transcription factors or", "factors or other", "or other kinases.", "other kinases. the", "kinases. the best", "the best known", "best known targets", "targets elk1", "elk1 ets1", "ets1 atf2", "atf2 mitf", "mitf mapkapk2", "mapkapk2 msk1", "msk1 rsk1/2/3", "rsk1/2/3 and mef2", "and mef2 are", "mef2 are annotated", "are annotated here.", "erk/mapk kinases have a", "kinases have a number", "have a number of", "a number of targets", "number of targets within", "of targets within the", "targets within the nucleus", "the nucleus usually", "nucleus usually transcription", "usually transcription factors or", "transcription factors or other", "factors or other kinases.", "or other kinases. the", "other kinases. the best", "kinases. the best known", "the best known targets", "known targets elk1", "msk1 rsk1/2/3 and", "rsk1/2/3 and mef2 are", "and mef2 are annotated", "mef2 are annotated here.", "erk/mapk kinases have a number", "kinases have a number of", "have a number of targets", "a number of targets within", "number of targets within the", "of targets within the nucleus", "within the nucleus usually", "the nucleus usually transcription", "nucleus usually transcription factors", "usually transcription factors or other", "transcription factors or other kinases.", "factors or other kinases. the", "or other kinases. the best", "other kinases. the best known", "kinases. the best known targets", "best known targets elk1", "targets elk1 ets1", "elk1 ets1 atf2", "ets1 atf2 mitf", "atf2 mitf mapkapk2", "mitf mapkapk2 msk1", "mapkapk2 msk1 rsk1/2/3", "msk1 rsk1/2/3 and mef2", "rsk1/2/3 and mef2 are annotated", "and mef2 are annotated here." ] }, { "record_id": "GLY_000594_1_857", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "199418", "r hsa", "hsa 199418", "r hsa 199418" ] }, { "record_id": "GLY_000594_1_857", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of the", "the pi3k/akt", "pi3k/akt network", "negative regulation of", "regulation of the", "of the pi3k/akt", "the pi3k/akt network", "negative regulation of the", "regulation of the pi3k/akt", "of the pi3k/akt network", "negative regulation of the pi3k/akt", "regulation of the pi3k/akt network", "network is", "is negatively", "negatively regulated", "regulated by", "by phosphatases", "phosphatases that", "that dephosphorylate", "dephosphorylate pip3", "thus hampering", "hampering akt", "akt activation.", "pi3k/akt network is", "network is negatively", "is negatively regulated", "negatively regulated by", "regulated by phosphatases", "by phosphatases that", "phosphatases that dephosphorylate", "that dephosphorylate pip3", "pip3 thus", "thus hampering akt", "hampering akt activation.", "the pi3k/akt network is", "pi3k/akt network is negatively", "network is negatively regulated", "is negatively regulated by", "negatively regulated by phosphatases", "regulated by phosphatases that", "by phosphatases that dephosphorylate", "phosphatases that dephosphorylate pip3", "dephosphorylate pip3 thus", "pip3 thus hampering", "thus hampering akt activation.", "the pi3k/akt network is negatively", "pi3k/akt network is negatively regulated", "network is negatively regulated by", "is negatively regulated by phosphatases", "negatively regulated by phosphatases that", "regulated by phosphatases that dephosphorylate", "by phosphatases that dephosphorylate pip3", "that dephosphorylate pip3 thus", "dephosphorylate pip3 thus hampering", "pip3 thus hampering akt" ] }, { "record_id": "GLY_000594_1_858", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "199920", "r hsa", "hsa 199920", "r hsa 199920" ] }, { "record_id": "GLY_000594_1_858", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "creb phosphorylation", "nerve growth", "growth factor", "activates multiple", "multiple signalling", "signalling pathways", "pathways that", "that mediate", "mediate the", "the phosphorylation", "phosphorylation of", "of creb", "creb at", "at the", "the critical", "critical regulatory", "regulatory site", "serine 133.", "133. creb", "phosphorylation at", "at serine", "serine 133", "133 is", "is a", "a crucial", "crucial event", "event in", "in neurotrophin", "neurotrophin signalling", "being mediated", "mediated by", "by erk/rsk", "erk/msk1 and", "and p38/mapkapk2", "p38/mapkapk2 pathways.", "pathways. several", "several kinases", "such as", "as msk1", "and mapkapk2", "are able", "able to", "to directly", "directly phosphorylate", "phosphorylate creb", "at s133.", "s133. msk1", "msk1 is", "is also", "also able", "to activate", "activate atf", "cyclic amp", "amp dependent", "dependent transcription", "transcription factor", "factor .", ". however", "the ngf", "ngf induced", "induced creb", "phosphorylation appears", "appears to", "to correlate", "correlate better", "better with", "with activation", "activation of", "of msk1", "msk1 rather", "rather than", "than rsk1/2/3", "or mapkapk2.", "mapkapk2. in", "in retrograde", "retrograde signalling", "creb occurs", "occurs within", "within 20", "20 minutes", "minutes after", "after neurotrophin", "neurotrophin stimulation", "stimulation of", "of distal", "distal axons.", "nerve growth factor", "factor ngf", "ngf activates", "activates multiple signalling", "multiple signalling pathways", "signalling pathways that", "pathways that mediate", "that mediate the", "mediate the phosphorylation", "the phosphorylation of", "phosphorylation of creb", "of creb at", "creb at the", "at the critical", "the critical regulatory", "critical regulatory site", "site serine", "serine 133. creb", "133. creb phosphorylation", "creb phosphorylation at", "phosphorylation at serine", "at serine 133", "serine 133 is", "133 is a", "is a crucial", "a crucial event", "crucial event in", "event in neurotrophin", "in neurotrophin signalling", "signalling being", "being mediated by", "mediated by erk/rsk", "erk/rsk erk/msk1", "erk/msk1 and p38/mapkapk2", "and p38/mapkapk2 pathways.", "p38/mapkapk2 pathways. several", "pathways. several kinases", "kinases such", "such as msk1", "msk1 rsk1/2/3", "rsk1/2/3 mapkapk1a/b/c", "mapkapk2 are", "are able to", "able to directly", "to directly phosphorylate", "directly phosphorylate creb", "phosphorylate creb at", "creb at s133.", "at s133. msk1", "s133. msk1 is", "msk1 is also", "is also able", "also able to", "able to activate", "to activate atf", "atf cyclic", "cyclic amp dependent", "amp dependent transcription", "dependent transcription factor", "transcription factor .", "factor . however", "however the", "the ngf induced", "ngf induced creb", "induced creb phosphorylation", "creb phosphorylation appears", "phosphorylation appears to", "appears to correlate", "to correlate better", "correlate better with", "better with activation", "with activation of", "activation of msk1", "of msk1 rather", "msk1 rather than", "rather than rsk1/2/3", "rsk1/2/3 or", "or mapkapk2. in", "mapkapk2. in retrograde", "in retrograde signalling", "signalling activation", "activation of creb", "of creb occurs", "creb occurs within", "occurs within 20", "within 20 minutes", "20 minutes after", "minutes after neurotrophin", "after neurotrophin stimulation", "neurotrophin stimulation of", "stimulation of distal", "of distal axons.", "growth factor ngf", "ngf activates multiple", "activates multiple signalling pathways", "multiple signalling pathways that", "signalling pathways that mediate", "pathways that mediate the", "that mediate the phosphorylation", "mediate the phosphorylation of", "the phosphorylation of creb", "phosphorylation of creb at", "of creb at the", "creb at the critical", "at the critical regulatory", "the critical regulatory site", "regulatory site serine", "site serine 133.", "serine 133. creb phosphorylation", "133. creb phosphorylation at", "creb phosphorylation at serine", "phosphorylation at serine 133", "at serine 133 is", "serine 133 is a", "133 is a crucial", "is a crucial event", "a crucial event in", "crucial event in neurotrophin", "event in neurotrophin signalling", "neurotrophin signalling being", "signalling being mediated", "being mediated by erk/rsk", "by erk/rsk erk/msk1", "erk/rsk erk/msk1 and", "erk/msk1 and p38/mapkapk2 pathways.", "and p38/mapkapk2 pathways. several", "p38/mapkapk2 pathways. several kinases", "several kinases such", "kinases such as", "as msk1 rsk1/2/3", "mapkapk1a/b/c and", "and mapkapk2 are", "mapkapk2 are able", "are able to directly", "able to directly phosphorylate", "to directly phosphorylate creb", "directly phosphorylate creb at", "phosphorylate creb at s133.", "creb at s133. msk1", "at s133. msk1 is", "s133. msk1 is also", "msk1 is also able", "is also able to", "also able to activate", "able to activate atf", "activate atf cyclic", "atf cyclic amp", "cyclic amp dependent transcription", "amp dependent transcription factor", "dependent transcription factor .", "transcription factor . however", ". however the", "however the ngf", "the ngf induced creb", "ngf induced creb phosphorylation", "induced creb phosphorylation appears", "creb phosphorylation appears to", "phosphorylation appears to correlate", "appears to correlate better", "to correlate better with", "correlate better with activation", "better with activation of", "with activation of msk1", "activation of msk1 rather", "of msk1 rather than", "msk1 rather than rsk1/2/3", "than rsk1/2/3 or", "rsk1/2/3 or mapkapk2.", "or mapkapk2. in retrograde", "mapkapk2. in retrograde signalling", "retrograde signalling activation", "signalling activation of", "activation of creb occurs", "of creb occurs within", "creb occurs within 20", "occurs within 20 minutes", "within 20 minutes after", "20 minutes after neurotrophin", "minutes after neurotrophin stimulation", "after neurotrophin stimulation of", "neurotrophin stimulation of distal", "stimulation of distal axons.", "nerve growth factor ngf", "factor ngf activates", "ngf activates multiple signalling", "activates multiple signalling pathways that", "multiple signalling pathways that mediate", "signalling pathways that mediate the", "pathways that mediate the phosphorylation", "that mediate the phosphorylation of", "mediate the phosphorylation of creb", "the phosphorylation of creb at", "phosphorylation of creb at the", "of creb at the critical", "creb at the critical regulatory", "at the critical regulatory site", "critical regulatory site serine", "regulatory site serine 133.", "site serine 133. creb", "serine 133. creb phosphorylation at", "133. creb phosphorylation at serine", "creb phosphorylation at serine 133", "phosphorylation at serine 133 is", "at serine 133 is a", "serine 133 is a crucial", "133 is a crucial event", "is a crucial event in", "a crucial event in neurotrophin", "crucial event in neurotrophin signalling", "in neurotrophin signalling being", "neurotrophin signalling being mediated", "signalling being mediated by", "mediated by erk/rsk erk/msk1", "by erk/rsk erk/msk1 and", "erk/rsk erk/msk1 and p38/mapkapk2", "erk/msk1 and p38/mapkapk2 pathways. several", "and p38/mapkapk2 pathways. several kinases", "pathways. several kinases such", "several kinases such as", "kinases such as msk1", "such as msk1 rsk1/2/3", "msk1 rsk1/2/3 mapkapk1a/b/c", "mapkapk1a/b/c and mapkapk2", "and mapkapk2 are able", "mapkapk2 are able to", "are able to directly phosphorylate", "able to directly phosphorylate creb", "to directly phosphorylate creb at", "directly phosphorylate creb at s133.", "phosphorylate creb at s133. msk1", "creb at s133. msk1 is", "at s133. msk1 is also", "s133. msk1 is also able", "msk1 is also able to", "is also able to activate", "also able to activate atf", "to activate atf cyclic", "activate atf cyclic amp", "atf cyclic amp dependent", "cyclic amp dependent transcription factor", "amp dependent transcription factor .", "dependent transcription factor . however", "factor . however the", ". however the ngf", "however the ngf induced", "the ngf induced creb phosphorylation", "ngf induced creb phosphorylation appears", "induced creb phosphorylation appears to", "creb phosphorylation appears to correlate", "phosphorylation appears to correlate better", "appears to correlate better with", "to correlate better with activation", "correlate better with activation of", "better with activation of msk1", "with activation of msk1 rather", "activation of msk1 rather than", "of msk1 rather than rsk1/2/3", "rather than rsk1/2/3 or", "than rsk1/2/3 or mapkapk2.", "rsk1/2/3 or mapkapk2. in", "or mapkapk2. in retrograde signalling", "in retrograde signalling activation", "retrograde signalling activation of", "signalling activation of creb", "activation of creb occurs within", "of creb occurs within 20", "creb occurs within 20 minutes", "occurs within 20 minutes after", "within 20 minutes after neurotrophin", "20 minutes after neurotrophin stimulation", "minutes after neurotrophin stimulation of", "after neurotrophin stimulation of distal", "neurotrophin stimulation of distal axons." ] }, { "record_id": "GLY_000594_1_859", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2022377", "r hsa", "hsa 2022377", "r hsa 2022377" ] }, { "record_id": "GLY_000594_1_859", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "metabolism of", "of angiotensinogen", "angiotensinogen to", "to angiotensins", "metabolism of angiotensinogen", "of angiotensinogen to", "angiotensinogen to angiotensins", "metabolism of angiotensinogen to", "of angiotensinogen to angiotensins", "metabolism of angiotensinogen to angiotensins", "a prohormone", "is synthesized", "synthesized and", "and secreted", "secreted mainly", "mainly by", "by the", "the liver", "liver but", "but also", "also from", "from other", "other tissues", "reviewed in", "in fyhrquist", "fyhrquist and", "and saijonmaa", "saijonmaa 2008", "cat and", "and touyz", "touyz 2011", "2011 .", ". renin", "an aspartyl", "aspartyl protease", "protease specific", "specific for", "for angiotensinogen", "is secreted", "secreted into", "into the", "the bloodstream", "bloodstream by", "by juxtaglomerular", "juxtaglomerular cells", "cells of", "of the", "the kidney", "kidney in", "in response", "response to", "to a", "a drop", "drop in", "in blood", "blood pressure.", "pressure. renin", "renin cleaves", "cleaves angiotensinogen", "to yield", "yield a", "a decapaptide", "angiotensin i", "angiotensin 1", "1 10", ". circulating", "circulating renin", "renin can", "can also", "also bind", "bind the", "the membrane", "membrane localized", "pro renin", "renin receptor", "which increases", "increases its", "its catalytic", "catalytic activity.", "activity. after", "after cleavage", "cleavage of", "to angiotensin", "i by", "by renin", "two c", "c terminal", "terminal amino", "amino acid", "acid residues", "residues of", "of angiotensin", "i are", "are removed", "removed by", "by angiotensin", "angiotensin converting", "converting enzyme", "located on", "on the", "the surface", "surface of", "of endothelial", "endothelial cells", "yield angiotensin", "angiotensin ii", "angiotensin 2", "1 8", "the active", "active peptide", "peptide that", "that causes", "causes vasoconstriction", "resorption of", "of sodium", "sodium and", "and chloride", "excretion of", "of potassium", "water retention", "and aldosterone", "aldosterone secretion.
more", "secretion.
more recently", "recently other", "more tissue", "tissue localized", "localized pathways", "pathways leading", "leading to", "ii and", "and alternative", "alternative derivatives", "derivatives of", "angiotensinogen have", "have been", "been identified", "in kramkowski", "kramkowski et", "et al.", "al. 2006", "kumar et", "al. 2007", "becari et", "al. 2011", ". chymase", "cathepsin g", "and cathepsin", "cathepsin x", "cathepsin z", "can each", "each cleave", "cleave angiotensin", "i to", "angiotensin ii.", "ii. angiotensin", "enzyme 2", "cleaves 1", "1 amino", "acid residue", "residue from", "from angiotensin", "1 9", "which can", "can be", "be cleaved", "cleaved by", "by ace", "ace to", "1 7", "7 .", ". ace2", "ace2 can", "also cleave", "ii to", ". neprilysin", "neprilysin can", "can cleave", "cleave either", "either angiotensin", "or angiotensin", ". angiotensin", "binds the", "the mas", "mas receptor", "mas proto", "proto oncogene", "produces effects", "effects opposite", "opposite to", "to those", "those produced", "produced by", "angiotensin ii.
aminopeptidase", "ii.
aminopeptidase a", "cleaves angiotensin", "angiotensin iii", "2 8", "which is", "is then", "then cleaved", "by aminopeptidase", "aminopeptidase n", "yielding angiotensin", "angiotensin iv", "3 8", "iv binds", "the at4", "at4 receptor", "oxytocinase .
inhibitors", ".
inhibitors of", "of renin", "e.g. aliskiren", "and ace", "e.g. lisinopril", "are currently", "currently used", "used to", "to treat", "treat hypertension", "in gerc", "gerc et", "al. 2009", "verdecchia et", "al. 2010", "alreja and", "and joseph", "joseph 2011", "angiotensinogen a", "prohormone is", "is synthesized and", "synthesized and secreted", "and secreted mainly", "secreted mainly by", "mainly by the", "by the liver", "the liver but", "liver but also", "but also from", "also from other", "from other tissues", "tissues reviewed", "reviewed in fyhrquist", "in fyhrquist and", "fyhrquist and saijonmaa", "and saijonmaa 2008", "2008 cat", "cat and touyz", "and touyz 2011", "touyz 2011 .", "2011 . renin", "renin an", "an aspartyl protease", "aspartyl protease specific", "protease specific for", "specific for angiotensinogen", "angiotensinogen is", "is secreted into", "secreted into the", "into the bloodstream", "the bloodstream by", "bloodstream by juxtaglomerular", "by juxtaglomerular cells", "juxtaglomerular cells of", "cells of the", "of the kidney", "the kidney in", "kidney in response", "in response to", "response to a", "to a drop", "a drop in", "drop in blood", "in blood pressure.", "blood pressure. renin", "pressure. renin cleaves", "renin cleaves angiotensinogen", "cleaves angiotensinogen to", "angiotensinogen to yield", "to yield a", "yield a decapaptide", "decapaptide angiotensin", "i angiotensin", "1 angiotensin", "10 .", ". circulating renin", "circulating renin can", "renin can also", "can also bind", "also bind the", "bind the membrane", "the membrane localized", "localized pro", "pro renin receptor", "receptor atp6ap2", "atp6ap2 which", "which increases its", "increases its catalytic", "its catalytic activity.", "catalytic activity. after", "activity. after cleavage", "after cleavage of", "cleavage of angiotensinogen", "angiotensinogen to angiotensin", "to angiotensin i", "angiotensin i by", "i by renin", "renin two", "two c terminal", "c terminal amino", "terminal amino acid", "amino acid residues", "acid residues of", "residues of angiotensin", "of angiotensin i", "angiotensin i are", "i are removed", "are removed by", "removed by angiotensin", "by angiotensin converting", "angiotensin converting enzyme", "enzyme ace", "located on the", "on the surface", "the surface of", "surface of endothelial", "of endothelial cells", "cells to", "to yield angiotensin", "yield angiotensin ii", "ii angiotensin", "2 angiotensin", "the active peptide", "active peptide that", "peptide that causes", "that causes vasoconstriction", "vasoconstriction resorption", "resorption of sodium", "of sodium and", "sodium and chloride", "chloride excretion", "excretion of potassium", "potassium water", "retention and", "and aldosterone secretion.
more", "aldosterone secretion.
more recently", "secretion.
more recently other", "other more", "more tissue localized", "tissue localized pathways", "localized pathways leading", "pathways leading to", "leading to angiotensin", "to angiotensin ii", "angiotensin ii and", "ii and alternative", "and alternative derivatives", "alternative derivatives of", "derivatives of angiotensinogen", "of angiotensinogen have", "angiotensinogen have been", "have been identified", "identified reviewed", "reviewed in kramkowski", "in kramkowski et", "kramkowski et al.", "et al. 2006", "2006 kumar", "kumar et al.", "et al. 2007", "2007 fyhrquist", "2008 becari", "becari et al.", "et al. 2011", "al. 2011 .", "2011 . chymase", "chymase cathepsin", "g and", "and cathepsin x", "x cathepsin", "z can", "can each cleave", "each cleave angiotensin", "cleave angiotensin i", "angiotensin i to", "i to yield", "yield angiotensin ii.", "angiotensin ii. angiotensin", "ii. angiotensin converting", "converting enzyme 2", "2 ace2", "ace2 cleaves", "cleaves 1 amino", "1 amino acid", "amino acid residue", "acid residue from", "residue from angiotensin", "from angiotensin i", "which can be", "can be cleaved", "be cleaved by", "cleaved by ace", "by ace to", "ace to yield", "1 7 .", "7 . ace2", ". ace2 can", "ace2 can also", "can also cleave", "also cleave angiotensin", "cleave angiotensin ii", "angiotensin ii to", "ii to yield", "7 . neprilysin", ". neprilysin can", "neprilysin can cleave", "can cleave either", "cleave either angiotensin", "9 or", "or angiotensin i", "7 . angiotensin", "7 binds", "binds the mas", "the mas receptor", "receptor mas1", "mas1 mas", "mas proto oncogene", "oncogene and", "and interestingly", "interestingly produces", "produces effects opposite", "effects opposite to", "opposite to those", "to those produced", "those produced by", "produced by angiotensin", "by angiotensin ii.
aminopeptidase", "angiotensin ii.
aminopeptidase a", "a apa", "apa enpep", "enpep cleaves", "cleaves angiotensin ii", "yield angiotensin iii", "iii angiotensin", "which is then", "is then cleaved", "then cleaved by", "cleaved by aminopeptidase", "by aminopeptidase n", "n apn", "apn anpep", "anpep yielding", "yielding angiotensin iv", "iv angiotensin", "angiotensin 3", "8 .", ". angiotensin iv", "angiotensin iv binds", "iv binds the", "binds the at4", "the at4 receptor", "receptor at4r", "at4r irap", "irap lnpep", "lnpep oxytocinase", "oxytocinase .
inhibitors of", ".
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more recently", "aldosterone secretion.
more recently other", "recently other more", "other more tissue", "more tissue localized pathways", "tissue localized pathways leading", "localized pathways leading to", "pathways leading to angiotensin", "leading to angiotensin ii", "to angiotensin ii and", "angiotensin ii and alternative", "ii and alternative derivatives", "and alternative derivatives of", "alternative derivatives of angiotensinogen", "derivatives of angiotensinogen have", "of angiotensinogen have been", "angiotensinogen have been identified", "been identified reviewed", "identified reviewed in", "reviewed in kramkowski et", "in kramkowski et al.", "kramkowski et al. 2006", "al. 2006 kumar", "2006 kumar et", "kumar et al. 2007", "al. 2007 fyhrquist", "2007 fyhrquist and", "saijonmaa 2008 becari", "2008 becari et", "becari et al. 2011", "et al. 2011 .", "al. 2011 . chymase", ". chymase cathepsin", "chymase cathepsin g", "cathepsin g and", "g and cathepsin", "cathepsin x cathepsin", "x cathepsin z", "cathepsin z can", "z can each", "can each cleave angiotensin", "each cleave angiotensin i", "cleave angiotensin i to", "angiotensin i to yield", "i to yield angiotensin", "to yield angiotensin ii.", "yield angiotensin ii. angiotensin", "angiotensin ii. angiotensin converting", "ii. angiotensin converting enzyme", "angiotensin converting enzyme 2", "enzyme 2 ace2", "ace2 cleaves 1", "cleaves 1 amino acid", "1 amino acid residue", "amino acid residue from", "acid residue from angiotensin", "residue from angiotensin i", "10 to", "yield angiotensin 1", "angiotensin 1 9", "9 which", "which can be cleaved", "can be cleaved by", "be cleaved by ace", "cleaved by ace to", "by ace to yield", "ace to yield angiotensin", "angiotensin 1 7", "1 7 . ace2", "7 . ace2 can", ". ace2 can also", "ace2 can also cleave", "can also cleave angiotensin", "also cleave angiotensin ii", "cleave angiotensin ii to", "angiotensin ii to yield", "ii to yield angiotensin", "1 7 . neprilysin", "7 . neprilysin can", ". neprilysin can cleave", "neprilysin can cleave either", "can cleave either angiotensin", "either angiotensin 1", "1 9 or", "9 or angiotensin", "or angiotensin i to", "1 7 . angiotensin", ". angiotensin 1", "1 7 binds", "7 binds the", "binds the mas receptor", "mas receptor mas1", "mas1 mas proto", "proto oncogene and", "interestingly produces effects", "produces effects opposite to", "effects opposite to those", "opposite to those produced", "to those produced by", "those produced by angiotensin", "produced by angiotensin ii.
aminopeptidase", "by angiotensin ii.
aminopeptidase a", "ii.
aminopeptidase a apa", "enpep cleaves angiotensin", "cleaves angiotensin ii to", "to yield angiotensin iii", "angiotensin iii angiotensin", "angiotensin 2 8", "which is then cleaved", "is then cleaved by", "then cleaved by aminopeptidase", "cleaved by aminopeptidase n", "aminopeptidase n apn", "anpep yielding angiotensin", "angiotensin iv angiotensin", "angiotensin 3 8", "3 8 .", "8 . angiotensin", ". angiotensin iv binds", "angiotensin iv binds the", "iv binds the at4", "binds the at4 receptor", "at4 receptor at4r", "lnpep oxytocinase .
inhibitors", "oxytocinase .
inhibitors of renin", "of renin e.g.", "renin e.g. aliskiren", "e.g. aliskiren and", "aliskiren and ace", "and ace e.g.", "ace e.g. lisinopril", "e.g. lisinopril ramipril", "ramipril are currently", "are currently used to", "currently used to treat", "used to treat hypertension", "treat hypertension reviewed", "hypertension reviewed in", "reviewed in gerc et", "in gerc et al.", "gerc et al. 2009", "al. 2009 verdecchia", "2009 verdecchia et", "verdecchia et al. 2010", "2010 alreja", "alreja and joseph 2011", "and joseph 2011 .", "a prohormone is synthesized", "prohormone is synthesized and", "is synthesized and secreted mainly", "synthesized and secreted mainly by", "and secreted mainly by the", "secreted mainly by the liver", "mainly by the liver but", "by the liver but also", "the liver but also from", "liver but also from other", "but also from other tissues", "from other tissues reviewed", "other tissues reviewed in", "tissues reviewed in fyhrquist", "reviewed in fyhrquist and saijonmaa", "in fyhrquist and saijonmaa 2008", "and saijonmaa 2008 cat", "saijonmaa 2008 cat and", "2008 cat and touyz", "cat and touyz 2011 .", "and touyz 2011 . renin", "2011 . renin an", ". renin an aspartyl", "renin an aspartyl protease", "an aspartyl protease specific for", "aspartyl protease specific for angiotensinogen", "specific for angiotensinogen is", "for angiotensinogen is secreted", "angiotensinogen is secreted into", "is secreted into the bloodstream", "secreted into the bloodstream by", "into the bloodstream by juxtaglomerular", "the bloodstream by juxtaglomerular cells", "bloodstream by juxtaglomerular cells of", "by juxtaglomerular cells of the", "juxtaglomerular cells of the kidney", "cells of the kidney in", "of the kidney in response", "the kidney in response to", "kidney in response to a", "in response to a drop", "response to a drop in", "to a drop in blood", "a drop in blood pressure.", "drop in blood pressure. renin", "in blood pressure. renin cleaves", "blood pressure. renin cleaves angiotensinogen", "pressure. renin cleaves angiotensinogen to", "renin cleaves angiotensinogen to yield", "cleaves angiotensinogen to yield a", "angiotensinogen to yield a decapaptide", "yield a decapaptide angiotensin", "a decapaptide angiotensin i", "angiotensin i angiotensin 1", "1 angiotensin 1", "1 10 . circulating", "10 . circulating renin", ". circulating renin can also", "circulating renin can also bind", "renin can also bind the", "can also bind the membrane", "also bind the membrane localized", "the membrane localized pro", "membrane localized pro renin", "localized pro renin receptor", "pro renin receptor atp6ap2", "receptor atp6ap2 which", "atp6ap2 which increases its", "which increases its catalytic activity.", "increases its catalytic activity. after", "its catalytic activity. after cleavage", "catalytic activity. after cleavage of", "activity. after cleavage of angiotensinogen", "after cleavage of angiotensinogen to", "cleavage of angiotensinogen to angiotensin", "of angiotensinogen to angiotensin i", "angiotensinogen to angiotensin i by", "to angiotensin i by renin", "i by renin two", "by renin two c", "renin two c terminal", "two c terminal amino acid", "c terminal amino acid residues", "terminal amino acid residues of", "amino acid residues of angiotensin", "acid residues of angiotensin i", "residues of angiotensin i are", "of angiotensin i are removed", "angiotensin i are removed by", "i are removed by angiotensin", "are removed by angiotensin converting", "removed by angiotensin converting enzyme", "angiotensin converting enzyme ace", "ace located on", "located on the surface of", "on the surface of endothelial", "the surface of endothelial cells", "of endothelial cells to", "endothelial cells to yield", "cells to yield angiotensin", "yield angiotensin ii angiotensin", "angiotensin ii angiotensin 2", "2 angiotensin 1", "8 the", "the active peptide that causes", "active peptide that causes vasoconstriction", "that causes vasoconstriction resorption", "causes vasoconstriction resorption of", "vasoconstriction resorption of sodium", "resorption of sodium and chloride", "sodium and chloride excretion", "and chloride excretion of", "chloride excretion of potassium", "excretion of potassium water", "of potassium water retention", "water retention and aldosterone", "retention and aldosterone secretion.
more", "and aldosterone secretion.
more recently other", "secretion.
more recently other more", "recently other more tissue", "other more tissue localized", "more tissue localized pathways leading", "tissue localized pathways leading to", "localized pathways leading to angiotensin", "pathways leading to angiotensin ii", "leading to angiotensin ii and", "to angiotensin ii and alternative", "angiotensin ii and alternative derivatives", "ii and alternative derivatives of", "and alternative derivatives of angiotensinogen", "alternative derivatives of angiotensinogen have", "derivatives of angiotensinogen have been", "of angiotensinogen have been identified", "have been identified reviewed", "been identified reviewed in", "identified reviewed in kramkowski", "reviewed in kramkowski et al.", "in kramkowski et al. 2006", "et al. 2006 kumar", "al. 2006 kumar et", "2006 kumar et al.", "et al. 2007 fyhrquist", "al. 2007 fyhrquist and", "2007 fyhrquist and saijonmaa", "and saijonmaa 2008 becari", "saijonmaa 2008 becari et", "2008 becari et al.", "becari et al. 2011 .", "et al. 2011 . chymase", "2011 . chymase cathepsin", ". chymase cathepsin g", "cathepsin g and cathepsin", "g and cathepsin x", "and cathepsin x cathepsin", "cathepsin x cathepsin z", "cathepsin z can each", "z can each cleave", "can each cleave angiotensin i", "each cleave angiotensin i to", "cleave angiotensin i to yield", "angiotensin i to yield angiotensin", "i to yield angiotensin ii.", "to yield angiotensin ii. angiotensin", "yield angiotensin ii. angiotensin converting", "angiotensin ii. angiotensin converting enzyme", "ii. angiotensin converting enzyme 2", "converting enzyme 2 ace2", "2 ace2 cleaves", "ace2 cleaves 1 amino", "cleaves 1 amino acid residue", "1 amino acid residue from", "amino acid residue from angiotensin", "acid residue from angiotensin i", "from angiotensin i angiotensin", "1 10 to", "10 to yield", "to yield angiotensin 1", "yield angiotensin 1 9", "1 9 which", "9 which can", "which can be cleaved by", "can be cleaved by ace", "be cleaved by ace to", "cleaved by ace to yield", "by ace to yield angiotensin", "yield angiotensin 1 7", "angiotensin 1 7 .", "1 7 . ace2 can", "7 . ace2 can also", ". ace2 can also cleave", "ace2 can also cleave angiotensin", "can also cleave angiotensin ii", "also cleave angiotensin ii to", "cleave angiotensin ii to yield", "angiotensin ii to yield angiotensin", "1 7 . neprilysin can", "7 . neprilysin can cleave", ". neprilysin can cleave either", "neprilysin can cleave either angiotensin", "cleave either angiotensin 1", "either angiotensin 1 9", "1 9 or angiotensin", "9 or angiotensin i", "or angiotensin i to yield", "7 . angiotensin 1", ". angiotensin 1 7", "1 7 binds the", "7 binds the mas", "the mas receptor mas1", "receptor mas1 mas", "mas1 mas proto oncogene", "mas proto oncogene and", "oncogene and interestingly", "and interestingly produces", "interestingly produces effects opposite", "produces effects opposite to those", "effects opposite to those produced", "opposite to those produced by", "to those produced by angiotensin", "those produced by angiotensin ii.
aminopeptidase", "produced by angiotensin ii.
aminopeptidase a", "angiotensin ii.
aminopeptidase a apa", "a apa enpep", "apa enpep cleaves", "enpep cleaves angiotensin ii", "cleaves angiotensin ii to yield", "ii to yield angiotensin iii", "yield angiotensin iii angiotensin", "iii angiotensin 2", "8 which", "which is then cleaved by", "is then cleaved by aminopeptidase", "then cleaved by aminopeptidase n", "by aminopeptidase n apn", "n apn anpep", "apn anpep yielding", "anpep yielding angiotensin iv", "yielding angiotensin iv angiotensin", "iv angiotensin 3", "3 8 . angiotensin", "8 . angiotensin iv", ". angiotensin iv binds the", "angiotensin iv binds the at4", "iv binds the at4 receptor", "the at4 receptor at4r", "receptor at4r irap", "at4r irap lnpep", "irap lnpep oxytocinase", "lnpep oxytocinase .
inhibitors of", ".
inhibitors of renin e.g.", "of renin e.g. aliskiren", "e.g. aliskiren and ace", "and ace e.g. lisinopril", "lisinopril ramipril are", "ramipril are currently used", "are currently used to treat", "currently used to treat hypertension", "to treat hypertension reviewed", "treat hypertension reviewed in", "hypertension reviewed in gerc", "reviewed in gerc et al.", "in gerc et al. 2009", "et al. 2009 verdecchia", "al. 2009 verdecchia et", "2009 verdecchia et al.", "al. 2010 alreja", "2010 alreja and", "alreja and joseph 2011 ." ] }, { "record_id": "GLY_000594_1_860", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2022854", "r hsa", "hsa 2022854", "r hsa 2022854" ] }, { "record_id": "GLY_000594_1_860", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "keratan sulfate", "sulfate biosynthesis", "keratan sulfate biosynthesis", "is the", "the best", "best characterised", "characterised keratan", "keratan 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activating", "dominant disorders described above.


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activating mutations in fgfr2 are", "mutations in fgfr2 are thought", "in fgfr2 are thought to", "fgfr2 are thought to contribute", "are thought to contribute to", "thought to contribute to receptor", "to contribute to receptor activation", "contribute to receptor activation through", "to receptor activation through diverse", "receptor activation through diverse mechanisms", "through diverse mechanisms including", "diverse mechanisms including constitutive", "mechanisms including constitutive ligand", "including constitutive ligand independent dimerization", "ligand independent dimerization robertson", "dimerization robertson 1998", "1998 expanded range", "expanded range and affinity for", "range and affinity for ligand", "affinity for ligand ibrahimi", "ligand ibrahimi 2004b", "ibrahimi 2004b yu", "2004b yu 2000", "yu 2000 and", "2000 and enhanced kinase", "enhanced kinase activity byron", "activity byron 2008", "byron 2008 chen", "2008 chen 2007" ] }, { "record_id": "GLY_000594_1_865", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "203615", "r hsa", "hsa 203615", "r hsa 203615" ] }, { "record_id": "GLY_000594_1_865", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "enos activation", "enos activity", "activity is", "is regulated", "regulated by", "by numerous", "numerous post", "post translational", "translational modifications", "modifications including", "including phosphorylation", "phosphorylation and", "and acylation", "which also", "also modulate", "modulate its", "its interactions", "interactions with", "with other", "other proteins", "proteins and", "and its", "its subcellular", "subcellular localization.

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in general", "following myristoylation", "myristoylation and", "and palmitoylation", "enos localizes", "localizes to", "to caveolae", "caveolae in", "in the", "the plasma", "plasma membrane", "where in", "in resting", "resting cells", "it is", "is bound", "bound to", "to caveolin", "caveolin and", "and remains", "remains inactive.", "inactive. several", "several agonists", "agonists that", "that raise", "raise intracellular", "intracellular calcium", "calcium concentrations", "concentrations promote", "promote calmodulin", "calmodulin binding", "binding to", "to enos", "enos and", "and the", "the dissociation", "dissociation of", "of caveolin", "caveolin from", "from the", "the enzyme", "leading to", "to an", "an activated", "activated enos", "enos calmodulin", "calmodulin complex.

phosphorylation", "complex.

phosphorylation plays", "plays a", "a significant", "significant role", "role in", "in regulating", "regulating enos", "especially the", "the phosphorylation", "phosphorylation of", "of ser1177", "located within", "within the", "the reductase", "reductase domain", "which increases", "increases enzyme", "enzyme activity", "activity by", "by enhancing", "enhancing reductase", "reductase activity", "activity and", "and calcium", "calcium sensitivity.", "sensitivity. in", "in unstimulated", "cultured endothelial", "endothelial cells", "ser1177 is", "is rapidly", "rapidly phosphorylated", "phosphorylated following", "following a", "a variety", "variety of", "of stimuli:", "stimuli: fluid", "fluid shear", "shear stress", "or bradykinin.", "the kinases", "kinases involved", "involved in", "in this", "this process", "process depend", "depend upon", "upon the", "the stimuli", "stimuli applied.", "for instance", "stress phosphorylates", "phosphorylates ser1177", "ser1177 by", "by activating", "activating akt", "akt and", "and pka", "insulin activates", "activates both", "both akt", "the amp", "amp activated", "activated protein", "protein kinase", "estrogen and", "and vegf", "vegf mainly", "mainly phosphorylate", "phosphorylate enos", "enos via", "via akt", "whereas the", "the bradykinin", "bradykinin induced", "induced phosphorylation", "is mediated", "mediated by", "by camkii.", "when ser1177", "is phosphorylated", "no production", "production is", "is increased", "increased several", "several fold", "fold above", "above basal", "basal levels.

the", "levels.

the phosphorylation", "of a", "a threonine", "threonine residue", "thr 495", "located in", "the cam", "cam binding", "binding domain", "is associated", "associated with", "with a", "a decrease", "decrease in", "in enos", "enos activity.", "activity. when", "when this", "this residue", "residue is", "is dephosphorylated", "substantially more", "more cam", "cam binds", "binds to", "and elevates", "elevates enzyme", "enzyme activity.", "activity. stimuli", "stimuli associated", "with dephosphorylation", "dephosphorylation of", "of thr495", "and ca2+", "ca2+ ionophores", "also increase", "increase ca2+", "ca2+ levels", "levels resulting", "resulting in", "of ser1177.

additional", "ser1177.

additional phosphorylation", "phosphorylation sites", "such as", "as ser114", "ser114 and", "and ser633", "and tyrosine", "tyrosine phosphorylation", "phosphorylation have", "have all", "all been", "been detected", "but their", "their functional", "functional relevance", "relevance remains", "remains unclear.", "unclear. it", "is speculated", "speculated that", "that the", "the tyrosine", "of enos", "enos is", "is unlikely", "unlikely to", "to affect", "affect enzyme", "activity directly", "but more", "more likely", "likely to", "to impact", "impact the", "the protein", "protein protein", "protein interactions", "with associated", "associated scaffolding", "scaffolding and", "and regulatory", "regulatory proteins.", "enos activity is", "activity is regulated", "is regulated by", "regulated by numerous", "by numerous post", "numerous post translational", "post translational modifications", "translational modifications including", "modifications including phosphorylation", "including phosphorylation and", "phosphorylation and acylation", "acylation which", "which also modulate", "also modulate its", "modulate its interactions", "its interactions with", "interactions with other", "with other proteins", "other proteins and", "proteins and its", "and its subcellular", "its subcellular localization.

in", "subcellular localization.

in general", "general following", "following myristoylation and", "myristoylation and palmitoylation", "palmitoylation enos", "enos localizes to", "localizes to caveolae", "to caveolae in", "caveolae in the", "in the plasma", "the plasma membrane", "membrane where", "where in resting", "in resting cells", "cells it", "it is bound", "is bound to", "bound to caveolin", "to caveolin and", "caveolin and remains", "and remains inactive.", "remains inactive. several", "inactive. several agonists", "several agonists that", "agonists that raise", "that raise intracellular", "raise intracellular calcium", "intracellular calcium concentrations", "calcium concentrations promote", "concentrations promote calmodulin", "promote calmodulin binding", "calmodulin binding to", "binding to enos", "to enos and", "enos and the", "and the dissociation", "the dissociation of", "dissociation of caveolin", "of caveolin from", "caveolin from the", "from the enzyme", "enzyme leading", "leading to an", "to an activated", "an activated enos", "activated enos calmodulin", "enos calmodulin complex.

phosphorylation", "calmodulin complex.

phosphorylation plays", "complex.

phosphorylation plays a", "plays a significant", "a significant role", "significant role in", "role in regulating", "in regulating enos", "regulating enos activity", "activity especially", "especially the phosphorylation", "the phosphorylation of", "phosphorylation of ser1177", "ser1177 located", "located within the", "within the reductase", "the reductase domain", "domain which", "which increases enzyme", "increases enzyme activity", "enzyme activity by", "activity by enhancing", "by enhancing reductase", "enhancing reductase activity", "reductase activity and", "activity and calcium", "and calcium sensitivity.", "calcium sensitivity. in", "sensitivity. in unstimulated", "unstimulated cultured", "cultured endothelial cells", "cells ser1177", "ser1177 is rapidly", "is rapidly phosphorylated", "rapidly phosphorylated following", "phosphorylated following a", "following a variety", "a variety of", "variety of stimuli:", "of stimuli: fluid", "stimuli: fluid shear", "fluid shear stress", "stress insulin", "insulin estrogen", "estrogen vegf", "vegf or", "bradykinin. the", "the kinases involved", "kinases involved in", "involved in this", "in this process", "this process depend", "process depend upon", "depend upon the", "upon the stimuli", "the stimuli applied.", "applied. for", "instance shear", "shear stress phosphorylates", "stress phosphorylates ser1177", "phosphorylates ser1177 by", "ser1177 by activating", "by activating akt", "activating akt and", "akt and pka", "pka insulin", "insulin activates both", "activates both akt", "both akt and", "akt and the", "and the amp", "the amp activated", "amp activated protein", "activated protein kinase", "kinase ampk", "estrogen and vegf", "and vegf mainly", "vegf mainly phosphorylate", "mainly phosphorylate enos", "phosphorylate enos via", "enos via akt", "akt whereas", "whereas the bradykinin", "the bradykinin induced", "bradykinin induced phosphorylation", "induced phosphorylation of", "of ser1177 is", "ser1177 is mediated", "is mediated by", "mediated by camkii.", "camkii. when", "when ser1177 is", "ser1177 is phosphorylated", "phosphorylated no", "no production is", "production is increased", "is increased several", "increased several fold", "several fold above", "fold above basal", "above basal levels.

the", "basal levels.

the phosphorylation", "levels.

the phosphorylation of", "phosphorylation of a", "of a threonine", "a threonine residue", "residue thr", "located in the", "in the cam", "the cam binding", "cam binding domain", "domain is", "is associated with", "associated with a", "with a decrease", "a decrease in", "decrease in enos", "in enos activity.", "enos activity. when", "activity. when this", "when this residue", "this residue is", "residue is dephosphorylated", "dephosphorylated substantially", "substantially more cam", "more cam binds", "cam binds to", "binds to enos", "enos and elevates", "and elevates enzyme", "elevates enzyme activity.", "enzyme activity. stimuli", "activity. stimuli associated", "stimuli associated with", "associated with dephosphorylation", "with dephosphorylation of", "dephosphorylation of thr495", "thr495 e.g.", "e.g. bradykinin", "bradykinin histamine", "histamine and", "and ca2+ ionophores", "ionophores also", "also increase ca2+", "increase ca2+ levels", "ca2+ levels resulting", "levels resulting in", "resulting in the", "in the phosphorylation", "phosphorylation of ser1177.

additional", "of ser1177.

additional phosphorylation", "ser1177.

additional phosphorylation sites", "sites such", "such as ser114", "as ser114 and", "ser114 and ser633", "ser633 and", "and tyrosine phosphorylation", "tyrosine phosphorylation have", "phosphorylation have all", "have all been", "all been detected", "detected but", "but their functional", "their functional relevance", "functional relevance remains", "relevance remains unclear.", "remains unclear. it", "unclear. it is", "it is speculated", "is speculated that", "speculated that the", "that the tyrosine", "the tyrosine phosphorylation", "tyrosine phosphorylation of", "phosphorylation of enos", "of enos is", "enos is unlikely", "is unlikely to", "unlikely to affect", "to affect enzyme", "affect enzyme activity", "enzyme activity directly", "directly but", "but more likely", "more likely to", "likely to impact", "to impact the", "impact the protein", "the protein protein", "protein protein interactions", "protein interactions with", "interactions with associated", "with associated scaffolding", "associated scaffolding and", "scaffolding and regulatory", "and regulatory proteins.", "enos activity is regulated", "activity is regulated by", "is regulated by numerous", "regulated by numerous post", "by numerous post translational", "numerous post translational modifications", "post translational modifications including", "translational modifications including phosphorylation", "modifications including phosphorylation and", "including phosphorylation and acylation", "and acylation which", "acylation which also", "which also modulate its", "also modulate its interactions", "modulate its interactions with", "its interactions with other", "interactions with other proteins", "with other proteins and", "other proteins and its", "proteins and its subcellular", "and its subcellular localization.

in", "its subcellular localization.

in general", "localization.

in general following", "general following myristoylation", "following myristoylation and palmitoylation", "and palmitoylation enos", "palmitoylation enos localizes", "enos localizes to caveolae", "localizes to caveolae in", "to caveolae in the", "caveolae in the plasma", "in the plasma membrane", "plasma membrane where", "membrane where in", "where in resting cells", "resting cells it", "cells it is", "it is bound to", "is bound to caveolin", "bound to caveolin and", "to caveolin and remains", "caveolin and remains inactive.", "and remains inactive. several", "remains inactive. several agonists", "inactive. several agonists that", "several agonists that raise", "agonists that raise intracellular", "that raise intracellular calcium", "raise intracellular calcium concentrations", "intracellular calcium concentrations promote", "calcium concentrations promote calmodulin", "concentrations promote calmodulin binding", "promote calmodulin binding to", "calmodulin binding to enos", "binding to enos and", "to enos and the", "enos and the dissociation", "and the dissociation of", "the dissociation of caveolin", "dissociation of caveolin from", "of caveolin from the", "caveolin from the enzyme", "the enzyme leading", "enzyme leading to", "leading to an activated", "to an activated enos", "an activated enos calmodulin", "activated enos calmodulin complex.

phosphorylation", "enos calmodulin complex.

phosphorylation plays", "calmodulin complex.

phosphorylation plays a", "complex.

phosphorylation plays a significant", "plays a significant role", "a significant role in", "significant role in regulating", "role in regulating enos", "in regulating enos activity", "enos activity especially", "activity especially the", "especially the phosphorylation of", "the phosphorylation of ser1177", "of ser1177 located", "ser1177 located within", "located within the reductase", "within the reductase domain", "reductase domain which", "domain which increases", "which increases enzyme activity", "increases enzyme activity by", "enzyme activity by enhancing", "activity by enhancing reductase", "by enhancing reductase activity", "enhancing reductase activity and", "reductase activity and calcium", "activity and calcium sensitivity.", "and calcium sensitivity. in", "calcium sensitivity. in unstimulated", "in unstimulated cultured", "unstimulated cultured endothelial", "endothelial cells ser1177", "cells ser1177 is", "ser1177 is rapidly phosphorylated", "is rapidly phosphorylated following", "rapidly phosphorylated following a", "phosphorylated following a variety", "following a variety of", "a variety of stimuli:", "variety of stimuli: fluid", "of stimuli: fluid shear", "stimuli: fluid shear stress", "shear stress insulin", "vegf or bradykinin.", "or bradykinin. the", "bradykinin. the kinases", "the kinases involved in", "kinases involved in this", "involved in this process", "in this process depend", "this process depend upon", "process depend upon the", "depend upon the stimuli", "upon the stimuli applied.", "stimuli applied. for", "applied. for instance", "for instance shear", "instance shear stress", "shear stress phosphorylates ser1177", "stress phosphorylates ser1177 by", "phosphorylates ser1177 by activating", "ser1177 by activating akt", "by activating akt and", "activating akt and pka", "and pka insulin", "pka insulin activates", "insulin activates both akt", "activates both akt and", "both akt and the", "akt and the amp", "and the amp activated", "the amp activated protein", "amp activated protein kinase", "protein kinase ampk", "ampk estrogen", "estrogen and vegf mainly", "and vegf mainly phosphorylate", "vegf mainly phosphorylate enos", "mainly phosphorylate enos via", "phosphorylate enos via akt", "via akt whereas", "akt whereas the", "whereas the bradykinin induced", "the bradykinin induced phosphorylation", "bradykinin induced phosphorylation of", "induced phosphorylation of ser1177", "phosphorylation of ser1177 is", "of ser1177 is mediated", "ser1177 is mediated by", "is mediated by camkii.", "by camkii. when", "camkii. when ser1177", "when ser1177 is phosphorylated", "is phosphorylated no", "phosphorylated no production", "no production is increased", "production is increased several", "is increased several fold", "increased several fold above", "several fold above basal", "fold above basal levels.

the", "above basal levels.

the phosphorylation", "basal levels.

the phosphorylation of", "levels.

the phosphorylation of a", "phosphorylation of a threonine", "of a threonine residue", "threonine residue thr", "residue thr 495", "495 located", "located in the cam", "in the cam binding", "the cam binding domain", "binding domain is", "domain is associated", "is associated with a", "associated with a decrease", "with a decrease in", "a decrease in enos", "decrease in enos activity.", "in enos activity. when", "enos activity. when this", "activity. when this residue", "when this residue is", "this residue is dephosphorylated", "is dephosphorylated substantially", "dephosphorylated substantially more", "substantially more cam binds", "more cam binds to", "cam binds to enos", "binds to enos and", "to enos and elevates", "enos and elevates enzyme", "and elevates enzyme activity.", "elevates enzyme activity. stimuli", "enzyme activity. stimuli associated", "activity. stimuli associated with", "stimuli associated with dephosphorylation", "associated with dephosphorylation of", "with dephosphorylation of thr495", "of thr495 e.g.", "histamine and ca2+", "ca2+ ionophores also", "ionophores also increase", "also increase ca2+ levels", "increase ca2+ levels resulting", "ca2+ levels resulting in", "levels resulting in the", "resulting in the phosphorylation", "in the phosphorylation of", "the phosphorylation of ser1177.

additional", "phosphorylation of ser1177.

additional phosphorylation", "of ser1177.

additional phosphorylation sites", "phosphorylation sites such", "sites such as", "such as ser114 and", "as ser114 and ser633", "and ser633 and", "ser633 and tyrosine", "and tyrosine phosphorylation have", "tyrosine phosphorylation have all", "phosphorylation have all been", "have all been detected", "been detected but", "detected but their", "but their functional relevance", "their functional relevance remains", "functional relevance remains unclear.", "relevance remains unclear. it", "remains unclear. it is", "unclear. it is speculated", "it is speculated that", "is speculated that the", "speculated that the tyrosine", "that the tyrosine phosphorylation", "the tyrosine phosphorylation of", "tyrosine phosphorylation of enos", "phosphorylation of enos is", "of enos is unlikely", "enos is unlikely to", "is unlikely to affect", "unlikely to affect enzyme", "to affect enzyme activity", "affect enzyme activity directly", "activity directly but", "directly but more", "but more likely to", "more likely to impact", "likely to impact the", "to impact the protein", "impact the protein protein", "the protein protein interactions", "protein protein interactions with", "protein interactions with associated", "interactions with associated scaffolding", "with associated scaffolding and", "associated scaffolding and regulatory", "scaffolding and regulatory proteins.", "enos activity is regulated by", "activity is regulated by numerous", "is regulated by numerous post", "regulated by numerous post translational", "by numerous post translational modifications", "numerous post translational modifications including", "post translational modifications including phosphorylation", "translational modifications including phosphorylation and", "modifications including phosphorylation and acylation", "phosphorylation and acylation which", "and acylation which also", "acylation which also modulate", "which also modulate its interactions", "also modulate its interactions with", "modulate its interactions with other", "its interactions with other proteins", "interactions with other proteins and", "with other proteins and its", "other proteins and its subcellular", "proteins and its subcellular localization.

in", "and its subcellular localization.

in general", "subcellular localization.

in general following", "localization.

in general following myristoylation", "general following myristoylation and", "myristoylation and palmitoylation enos", "and palmitoylation enos localizes", "palmitoylation enos localizes to", "enos localizes to caveolae in", "localizes to caveolae in the", "to caveolae in the plasma", "caveolae in the plasma membrane", "the plasma membrane where", "plasma membrane where in", "membrane where in resting", "in resting cells it", "resting cells it is", "cells it is bound", "it is bound to caveolin", "is bound to caveolin and", "bound to caveolin and remains", "to caveolin and remains inactive.", "caveolin and remains inactive. several", "and remains inactive. several agonists", "remains inactive. several agonists that", "inactive. several agonists that raise", "several agonists that raise intracellular", "agonists that raise intracellular calcium", "that raise intracellular calcium concentrations", "raise intracellular calcium concentrations promote", "intracellular calcium concentrations promote calmodulin", "calcium concentrations promote calmodulin binding", "concentrations promote calmodulin binding to", "promote calmodulin binding to enos", "calmodulin binding to enos and", "binding to enos and the", "to enos and the dissociation", "enos and the dissociation of", "and the dissociation of caveolin", "the dissociation of caveolin from", "dissociation of caveolin from the", "of caveolin from the enzyme", "from the enzyme leading", "the enzyme leading to", "enzyme leading to an", "leading to an activated enos", "to an activated enos calmodulin", "an activated enos calmodulin complex.

phosphorylation", "activated enos calmodulin complex.

phosphorylation plays", "enos calmodulin complex.

phosphorylation plays a", "calmodulin complex.

phosphorylation plays a significant", "complex.

phosphorylation plays a significant role", "plays a significant role in", "a significant role in regulating", "significant role in regulating enos", "role in regulating enos activity", "regulating enos activity especially", "enos activity especially the", "activity especially the phosphorylation", "especially the phosphorylation of ser1177", "phosphorylation of ser1177 located", "of ser1177 located within", "ser1177 located within the", "located within the reductase domain", "the reductase domain which", "reductase domain which increases", "domain which increases enzyme", "which increases enzyme activity by", "increases enzyme activity by enhancing", "enzyme activity by enhancing reductase", "activity by enhancing reductase activity", "by enhancing reductase activity and", "enhancing reductase activity and calcium", "reductase activity and calcium sensitivity.", "activity and calcium sensitivity. in", "and calcium sensitivity. in unstimulated", "sensitivity. in unstimulated cultured", "in unstimulated cultured endothelial", "unstimulated cultured endothelial cells", "cultured endothelial cells ser1177", "endothelial cells ser1177 is", "cells ser1177 is rapidly", "ser1177 is rapidly phosphorylated following", "is rapidly phosphorylated following a", "rapidly phosphorylated following a variety", "phosphorylated following a variety of", "following a variety of stimuli:", "a variety of stimuli: fluid", "variety of stimuli: fluid shear", "of stimuli: fluid shear stress", "fluid shear stress insulin", "stress insulin estrogen", "insulin estrogen vegf", "estrogen vegf or", "or bradykinin. the kinases", "bradykinin. the kinases involved", "the kinases involved in this", "kinases involved in this process", "involved in this process depend", "in this process depend upon", "this process depend upon the", "process depend upon the stimuli", "depend upon the stimuli applied.", "the stimuli applied. for", "stimuli applied. for instance", "for instance shear stress", "instance shear stress phosphorylates", "shear stress phosphorylates ser1177 by", "stress phosphorylates ser1177 by activating", "phosphorylates ser1177 by activating akt", "ser1177 by activating akt and", "by activating akt and pka", "akt and pka insulin", "and pka insulin activates", "pka insulin activates both", "insulin activates both akt and", "activates both akt and the", "both akt and the amp", "akt and the amp activated", "and the amp activated protein", "the amp activated protein kinase", "activated protein kinase ampk", "ampk estrogen and", "estrogen and vegf mainly phosphorylate", "and vegf mainly phosphorylate enos", "vegf mainly phosphorylate enos via", "mainly phosphorylate enos via akt", "enos via akt whereas", "via akt whereas the", "akt whereas the bradykinin", "whereas the bradykinin induced phosphorylation", "the bradykinin induced phosphorylation of", "bradykinin induced phosphorylation of ser1177", "induced phosphorylation of ser1177 is", "phosphorylation of ser1177 is mediated", "of ser1177 is mediated by", "ser1177 is mediated by camkii.", "mediated by camkii. when", "by camkii. when ser1177", "camkii. when ser1177 is", "ser1177 is phosphorylated no", "is phosphorylated no production", "phosphorylated no production is", "no production is increased several", "production is increased several fold", "is increased several fold above", "increased several fold above basal", "several fold above basal levels.

the", "fold above basal levels.

the phosphorylation", "above basal levels.

the phosphorylation of", "basal levels.

the phosphorylation of a", "levels.

the phosphorylation of a threonine", "phosphorylation of a threonine residue", "a threonine residue thr", "threonine residue thr 495", "thr 495 located", "495 located in", "located in the cam binding", "in the cam binding domain", "cam binding domain is", "binding domain is associated", "domain is associated with", "is associated with a decrease", "associated with a decrease in", "with a decrease in enos", "a decrease in enos activity.", "decrease in enos activity. when", "in enos activity. when this", "enos activity. when this residue", "activity. when this residue is", "when this residue is dephosphorylated", "residue is dephosphorylated substantially", "is dephosphorylated substantially more", "dephosphorylated substantially more cam", "substantially more cam binds to", "more cam binds to enos", "cam binds to enos and", "binds to enos and elevates", "to enos and elevates enzyme", "enos and elevates enzyme activity.", "and elevates enzyme activity. stimuli", "elevates enzyme activity. stimuli associated", "enzyme activity. stimuli associated with", "activity. stimuli associated with dephosphorylation", "stimuli associated with dephosphorylation of", "associated with dephosphorylation of thr495", "dephosphorylation of thr495 e.g.", "thr495 e.g. bradykinin", "e.g. bradykinin histamine", "bradykinin histamine and", "histamine and ca2+ ionophores", "and ca2+ ionophores also", "ca2+ ionophores also increase", "ionophores also increase ca2+", "also increase ca2+ levels resulting", "increase ca2+ levels resulting in", "ca2+ levels resulting in the", "levels resulting in the phosphorylation", "resulting in the phosphorylation of", "in the phosphorylation of ser1177.

additional", "the phosphorylation of ser1177.

additional phosphorylation", "phosphorylation of ser1177.

additional phosphorylation sites", "ser1177.

additional phosphorylation sites such", "phosphorylation sites such as", "sites such as ser114", "such as ser114 and ser633", "ser114 and ser633 and", "and ser633 and tyrosine", "ser633 and tyrosine phosphorylation", "and tyrosine phosphorylation have all", "tyrosine phosphorylation have all been", "phosphorylation have all been detected", "all been detected but", "been detected but their", "detected but their functional", "but their functional relevance remains", "their functional relevance remains unclear.", "functional relevance remains unclear. it", "relevance remains unclear. it is", "remains unclear. it is speculated", "unclear. it is speculated that", "it is speculated that the", "is speculated that the tyrosine", "speculated that the tyrosine phosphorylation", "that the tyrosine phosphorylation of", "the tyrosine phosphorylation of enos", "tyrosine phosphorylation of enos is", "phosphorylation of enos is unlikely", "of enos is unlikely to", "enos is unlikely to affect", "is unlikely to affect enzyme", "unlikely to affect enzyme activity", "to affect enzyme activity directly", "enzyme activity directly but", "activity directly but more", "directly but more likely", "but more likely to impact", "more likely to impact the", "likely to impact the protein", "to impact the protein protein", "impact the protein protein interactions", "the protein protein interactions with", "protein protein interactions with associated", "protein interactions with associated scaffolding", "interactions with associated scaffolding and", "with associated scaffolding and regulatory", "associated scaffolding and regulatory proteins." ] }, { "record_id": "GLY_000594_1_866", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2046105", "r hsa", "hsa 2046105", "r hsa 2046105" ] }, { "record_id": "GLY_000594_1_866", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "linoleic acid", "acid la", "la metabolism", "linoleic acid la", "acid la metabolism", "18:2 n", "n 6", "is an", "an omega", "omega 6", "6 fatty", "fatty acid", "acid obtained", "obtained through", "through diet", "mainly from", "from vegetable", "vegetable oils.", "oils. omega", "fatty acids", "acids helps", "helps stimulate", "stimulate skin", "skin and", "and hair", "hair growth", "maintain bone", "bone health", "regulate metabolism", "and maintain", "maintain the", "the reproductive", "reproductive system.", "system. all", "all the", "the desaturation", "desaturation and", "and elongation", "elongation steps", "steps occur", "occur in", "in the", "the endoplasmic", "endoplasmic reticulum", "except for", "for the", "the final", "final step", "step which", "which requires", "requires translocation", "translocation to", "to peroxisomes", "peroxisomes for", "for partial", "partial beta", "beta oxidation.", "oxidation. the", "the linoleic", "acid pathway", "pathway involves", "involves the", "the following", "following steps:", "steps: 18:2", ">18:3 n", "> 20:3", "20:3 n", ">20:4 n", ">22:4 n", ">24:4 n", ">24:5 n", ">22:5 n", "6 .", ". two", "two desaturation", "desaturation enzymes", "enzymes are", "are involved", "involved in", "in this", "this process:", "process: delta", "delta 6", "6 desaturase", "desaturase which", "which converts", "converts 18:2", "to 18:3", "and 24:4", "24:4 n", "to 24:5", "24:5 n", "and delta", "delta 5", "5 desaturase", "converts 20:3", "to 20:4", "20:4 n", "sprecher 2002", "2002 .", "la 18:2", "18:2 n 6", "is an omega", "an omega 6", "omega 6 fatty", "6 fatty acid", "fatty acid obtained", "acid obtained through", "obtained through diet", "diet mainly", "mainly from vegetable", "from vegetable oils.", "vegetable oils. omega", "oils. omega 6", "6 fatty acids", "fatty acids helps", "acids helps stimulate", "helps stimulate skin", "stimulate skin and", "skin and hair", "and hair growth", "growth maintain", "maintain bone health", "health regulate", "metabolism 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and", "and 12 oxo", "12 oxo eicosatetraenoate", "oxoete are", "are formed after", "formed after the", "after the initial", "the initial step", "initial step of", "step of arachidonate", "of arachidonate oxidation", "arachidonate oxidation by", "oxidation by the", "by the arachidonate", "the arachidonate 12", "arachidonate 12 and", "12 and 15", "and 15 lipoxygenases", "lipoxygenases alox12", "alox12 alox12b", "alox12b and alox15", "and alox15 respectively", "alox15 respectively .", ". this", "this part of", "part of the", "of the pathway", "the pathway is", "pathway is bifurcated", "is bifurcated at", "bifurcated at the", "at the level", "the level of", "level of 12s", "of 12s hydroperoxy", "12s hydroperoxy eicosatetraenoate", "eicosatetraenoate 12s", "which can either", "can either be", "either be reduced", "be reduced to", "reduced to 12s", "to 12s hydro", "12s hydro eicosatetraenoate", "hete or", "or converted to", "converted to hepoxilins", "hepoxilins buczynski", "buczynski et al.", "et al. 2009", "2009 vance", "vance & vance", "& vance 2008", "vance 2008 .", "the 12 eicosatetraenoic acids:", "12 eicosatetraenoic acids: 12", "eicosatetraenoic acids: 12 hydroperoxy", "acids: 12 hydroperoxy eicosatetraenoate", "hydroperoxy eicosatetraenoate 12", "eicosatetraenoate 12 hpete", "hpete 12", "12 hydroxyeicosatetraenoate 12", "hydroxyeicosatetraenoate 12 hete", "12 hete and", "hete and 12", "and 12 oxo eicosatetraenoate", "oxo eicosatetraenoate 12", "eicosatetraenoate 12 oxoete", "12 oxoete are", "oxoete are formed", "are formed after the", "formed after the initial", "after the initial step", "the initial step of", "initial step of arachidonate", "step of arachidonate oxidation", "of arachidonate oxidation by", "arachidonate oxidation by the", "oxidation by the arachidonate", "by the arachidonate 12", "the arachidonate 12 and", "arachidonate 12 and 15", "12 and 15 lipoxygenases", "15 lipoxygenases alox12", "alox12 alox12b and", "alox12b and alox15 respectively", "and alox15 respectively .", "respectively . this", ". this part", "this part of the", "part of the pathway", "of the pathway is", "the pathway is bifurcated", "pathway is bifurcated at", "is bifurcated at the", "bifurcated at the level", "at the level of", "the level of 12s", "level of 12s hydroperoxy", "of 12s hydroperoxy eicosatetraenoate", "hydroperoxy eicosatetraenoate 12s", "eicosatetraenoate 12s hpete", "hpete which", "which can either be", "can either be reduced", "either be reduced to", "be reduced to 12s", "reduced to 12s hydro", "to 12s hydro eicosatetraenoate", "hydro eicosatetraenoate 12s", "eicosatetraenoate 12s hete", "12s hete or", "hete or converted", "or converted to hepoxilins", "to hepoxilins buczynski", "hepoxilins buczynski et", "buczynski et al. 2009", "al. 2009 vance", "2009 vance &", "vance & vance 2008", "& vance 2008 .", "the 12 eicosatetraenoic acids: 12", "12 eicosatetraenoic acids: 12 hydroperoxy", "eicosatetraenoic acids: 12 hydroperoxy eicosatetraenoate", "12 hydroperoxy eicosatetraenoate 12", "hydroperoxy eicosatetraenoate 12 hpete", "12 hpete 12", "hpete 12 hydroxyeicosatetraenoate", "12 hydroxyeicosatetraenoate 12 hete", "12 hete and 12", "hete and 12 oxo", "12 oxo eicosatetraenoate 12", "oxo eicosatetraenoate 12 oxoete", "12 oxoete are formed", "oxoete are formed after", "are formed after the initial", "formed after the initial step", "after the initial step of", "the initial step of arachidonate", "initial step of arachidonate oxidation", "step of arachidonate oxidation by", "of arachidonate oxidation by the", "arachidonate oxidation by the arachidonate", "oxidation by the arachidonate 12", "by the arachidonate 12 and", "the arachidonate 12 and 15", "arachidonate 12 and 15 lipoxygenases", "and 15 lipoxygenases alox12", "lipoxygenases alox12 alox12b", "alox12 alox12b and alox15", "alox12b and alox15 respectively .", "alox15 respectively . this", "respectively . this part", ". this part of", "this part of the pathway", "part of the pathway is", "of the pathway is bifurcated", "the pathway is bifurcated at", "pathway is bifurcated at the", "is bifurcated at the level", "bifurcated at the level of", "at the level of 12s", "the level of 12s hydroperoxy", "level of 12s hydroperoxy eicosatetraenoate", "12s hydroperoxy eicosatetraenoate 12s", "hydroperoxy eicosatetraenoate 12s hpete", "12s hpete which", "hpete which can", "which can either be reduced", "can either be reduced to", "either be reduced to 12s", "be reduced to 12s hydro", "reduced to 12s hydro eicosatetraenoate", "12s hydro eicosatetraenoate 12s", "hydro eicosatetraenoate 12s hete", "12s hete or converted", "hete or converted to", "converted to hepoxilins buczynski", "to hepoxilins buczynski et", "hepoxilins buczynski et al.", "et al. 2009 vance", "al. 2009 vance &", "2009 vance & vance", "vance & vance 2008 ." ] }, { "record_id": "GLY_000594_1_882", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142789", "r hsa", "hsa 2142789", "r hsa 2142789" ] }, { "record_id": "GLY_000594_1_882", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ubiquinol biosynthesis", "the length", "length of", "of the", "the polyisoprenoid", "polyisoprenoid chain", "chain of", "of ubiquinone", "aka coenzyme", "coenzyme q", "varies depending", "depending on", "on the", "the species", "species involved:", "involved: it", "it is", "is 6", "6 in", "in budding", "budding yeast", "saccharomyces cerevisiae", "and 10", "10 in", "in humans", "coq10 .", ". most", "most ubiquinone", "ubiquinone is", "is naturally", "naturally reduced", "reduced to", "to ubiquinol", "coq10h2 in", "and this", "this form", "form dominates", "dominates in", "in human", "human tissues.", "tissues. it", "it functions", "functions as", "as a", "a ubiquitous", "ubiquitous coenzyme", "coenzyme in", "in redox", "redox reactions", "and has", "has a", "a central", "central role", "role in", "in the", "the electron", "electron transport", "transport chain", "the inner", "inner mitochondrial", "mitochondrial membrane.to", "membrane.to shuttle", "shuttle electrons", "electrons from", "from complexes", "complexes i", "i and", "and ii", "ii to", "to complex", "complex iii.", "iii. it", "it also", "also acts", "acts as", "a cofactor", "cofactor for", "for biosynthetic", "biosynthetic and", "and catabolic", "catabolic reactions", "detoxifies damaging", "damaging lipid", "lipid species", "and engages", "engages in", "in cellular", "cellular signaling", "signaling and", "and oxygen", "oxygen sensing.", "sensing. in", "in eukaryotes", "ubiquinones/ubiquinols are", "are also", "also found", "found in", "in other", "other membranes", "membranes such", "such as", "as the", "the endoplasmic", "endoplasmic reticulum", "golgi vesicles", "peroxisomes and", "and the", "the plasma", "plasma membrane", "reviewed in", "in guerra", "guerra &", "& pagliarini", "2023 .

ubiquinol/ubiquinone", ".

ubiquinol/ubiquinone is", "is synthesized", "synthesized in", "the following", "following way.", "way. initially", "mitochondrial 4", "4 hydroxyphenylpyruvate", "hydroxyphenylpyruvate dioxygenase", "dioxygenase like", "like protein", "processes 4", "4 hydroxphenylpyruvate", "4 hydroxymandelate", "4 hma", "hma .", ". hpdl", "hpdl defects", "defects lead", "lead to", "to coq10", "coq10 deficiency.", "deficiency. the", "the hpdl", "hpdl product", "product 4", "hma is", "is a", "a precursor", "precursor for", "for the", "the synthesis", "synthesis of", "of 4", "4 hydroxybenzoate", "from which", "which the", "the coq10", "coq10 head", "head group", "group is", "is derived", "banh et", "et al.", "2021 .", ". because", "because hpdl", "hpdl is", "a mitochondrial", "mitochondrial protein", "cytosolic hpp", "hpp from", "from tyrosine", "tyrosine catabolism", "catabolism must", "must either", "either be", "be imported", "imported by", "by a", "a yet", "yet unknown", "unknown transport", "transport mechanism", "mechanism or", "or mitochondrial", "mitochondrial hpp", "hpp could", "could be", "be the", "the product", "product of", "of an", "an unknown", "unknown mitochondrial", "mitochondrial reaction", "husain et", "in staiano", "staiano et", "2023 .", ". a", "a polyprenyl", "polyprenyl diphosphate", "diphosphate synthase", "pdss1 2", "assembles the", "polyisoprenoid tail.", "tail. next", "hydroxybenzoate polyprenyltransferase", "catalyzes the", "the formation", "formation of", "the covalent", "covalent linkage", "linkage between", "between phb", "phb and", "polyisoprenoid tail", "tail to", "to produce", "produce 4", "4 hydroxy", "hydroxy 3", "3 polyprenyl", "polyprenyl benzoic", "benzoic acid", "acid intermediate", "3 decaprenyl", "decaprenyl 4", "4 hydroxybenzoic", "hydroxybenzoic acid", "acid in", "humans .", ". modifications", "modifications of", "the aromatic", "aromatic ring", "ring follow", "follow and", "and involve", "involve an", "an oxidative", "oxidative decarboxylation", "two hydroxylations", "two o", "o methylations", "one c", "c methylation.", "methylation. this", "this series", "series of", "of reactions", "which precise", "precise order", "order is", "is not", "not fully", "fully established", "especially regarding", "regarding the", "the oxidative", "decarboxylation step", "pelosi et", "nicoll et", "yield the", "the fully", "fully substituted", "substituted hydroquinone", "2023 .


homologs", ".


homologs of", "the core", "core enzymes", "enzymes coq3", "and coq9", "coq9 have", "have been", "been shown", "shown to", "to form", "form a", "a membrane", "membrane localized", "localized multienzyme", "multienzyme complex", "\\coq synthome\\", "in yeast", "he et", "2014 .", ". there", "there is", "is some", "some evidence", "evidence of", "of such", "such a", "a complex", "called complex", "complex q", "floyd et", "2016 .", "complex was", "was reconstituted", "reconstituted in", "in vitro", "vitro with", "with ancestral", "ancestral versions", "versions of", "of coq3", "coq3 7", "7 and", "and was", "was able", "able to", "to convert", "convert a", "a short", "short chain", "chain analog", "analog of", "of dhb", "3 methylbut", "methylbut 2", "2 en", "en 1", "1 yl", "yl benzoic", "into coq1", "2024 .", ". coq8a", "coq8a and", "and coq8b", "coq8b proteins", "proteins may", "may contribute", "contribute to", "to the", "formation and", "and functionality", "functionality of", "of this", "this complex", "as they", "they can", "can bind", "bind to", "to most", "most core", "and as", "as coq8b", "coq8b increased", "increased the", "the in", "vitro activity", "activity of", "of coq6", "coq6 via", "via phosphorylation", "phosphorylation of", "2024 ..

parts", "..

parts of", "of coq10", "coq10 synthesis", "synthesis may", "may also", "also occur", "occur in", "the golgi", "golgi and", "and endoplasmic", "reticulum membranes", "adding to", "the cellular", "cellular membrane", "membrane coq10", "coq10 pool.", "pool. the", "the relevance", "relevance of", "such processes", "processes seems", "seems minor", "kal\u00e9n et", "2023 .the", ".the precise", "precise function", "function of", "of two", "two other", "other genes", "coq10a and", "and coq10b", "which appear", "appear to", "to be", "be quinone", "quinone binding", "binding proteins", "is still", "still under", "under investigation.", "investigation. most", "most of", "the time", "coq10 is", "is transported", "transported out", "out of", "the mitochondrion", "mitochondrion and", "and to", "membrane by", "by isoforms", "isoforms of", "the stard7", "stard7 lipid", "lipid carrier", "in guile", "guile et", "2023 .

coq10", ".

coq10 deficiency", "which can", "can result", "result from", "from reduced", "reduced activity", "of any", "any biosynthesis", "biosynthesis core", "enzymes or", "or the", "the coq8a", "has significant", "significant implications.", "implications. it", "is associated", "associated with", "with several", "several inherited", "inherited metabolic", "metabolic disorders", "the phenotypes", "phenotypes of", "of which", "which are", "are extremely", "extremely heterogeneous.", "heterogeneous. these", "these disorders", "disorders range", "range from", "from fatal", "fatal neonatal", "neonatal presentations", "presentations with", "with multisystem", "multisystem involvement", "involvement to", "to adult", "adult onset", "onset isolated", "isolated myopathy.", "myopathy. however", "in many", "many cases", "the symptoms", "symptoms can", "can be", "be ameliorated", "ameliorated by", "by nutritional", "nutritional supplementation", "supplementation with", "with coq10", "in quinzii", "quinzii et", "the length of", "length of the", "of the polyisoprenoid", "the polyisoprenoid chain", "polyisoprenoid chain of", "chain of ubiquinone", "ubiquinone aka", "aka coenzyme q", "q coq", "varies depending on", "depending on the", "on the species", "the species involved:", "species involved: it", "involved: it is", "it is 6", "is 6 in", "6 in budding", "in budding yeast", "yeast saccharomyces", "coq6 and", "and 10 in", "10 in humans", "humans coq10", "coq10 . most", ". most ubiquinone", "most ubiquinone is", "ubiquinone is naturally", "is naturally reduced", "naturally reduced to", "reduced to ubiquinol", "ubiquinol coq10h2", "coq10h2 in humans", "and this form", "this form dominates", "form dominates in", "dominates in human", "in human tissues.", "human tissues. it", "tissues. it functions", "it functions as", "functions as a", "as a ubiquitous", "a ubiquitous coenzyme", "ubiquitous coenzyme in", "coenzyme in redox", "in redox reactions", "reactions and", "and has a", "has a central", "a central role", "central role in", "role in the", "in the electron", "the electron transport", "electron transport chain", "transport chain of", "chain of the", "of the inner", "the inner mitochondrial", "inner mitochondrial membrane.to", "mitochondrial membrane.to shuttle", "membrane.to shuttle electrons", "shuttle electrons from", "electrons from complexes", "from complexes i", "complexes i and", "i and ii", "and ii to", "ii to complex", "to complex iii.", "complex iii. it", "iii. it also", "it also acts", "also acts as", "acts as a", "as a cofactor", "a cofactor for", "cofactor for biosynthetic", "for biosynthetic and", "biosynthetic and catabolic", "and catabolic reactions", "reactions detoxifies", "detoxifies damaging lipid", "damaging lipid species", "species and", "and engages in", "engages in cellular", "in cellular signaling", "cellular signaling and", "signaling and oxygen", "and oxygen sensing.", "oxygen sensing. in", "sensing. in eukaryotes", "eukaryotes ubiquinones/ubiquinols", "ubiquinones/ubiquinols are also", "are also found", "also found in", "found in other", "in other membranes", "other membranes such", "membranes such as", "such as the", "as the endoplasmic", "the endoplasmic reticulum", "reticulum golgi", "vesicles lysosomes", "lysosomes peroxisomes", "peroxisomes and the", "and the plasma", "the plasma membrane", "membrane reviewed", "reviewed in guerra", "in guerra &", "guerra & pagliarini", "pagliarini 2023", "2023 .

ubiquinol/ubiquinone is", ".

ubiquinol/ubiquinone is synthesized", "is synthesized in", "synthesized in the", "in the following", "the following way.", "following way. initially", "initially mitochondrial", "mitochondrial 4 hydroxyphenylpyruvate", "4 hydroxyphenylpyruvate dioxygenase", "hydroxyphenylpyruvate dioxygenase like", "dioxygenase like protein", "protein hpdl", "hpdl processes", "processes 4 hydroxphenylpyruvate", "hydroxphenylpyruvate hpp", "hpp hppa", "hppa to", "to s", "s 4", "hydroxymandelate 4", "4 hma .", "hma . hpdl", ". hpdl defects", "hpdl defects lead", "defects lead to", "lead to coq10", "to coq10 deficiency.", "coq10 deficiency. the", "deficiency. the hpdl", "the hpdl product", "hpdl product 4", "product 4 hma", "4 hma is", "hma is a", "is a precursor", "a precursor for", "precursor for the", "for the synthesis", "the synthesis of", "synthesis of 4", "of 4 hydroxybenzoate", "hydroxybenzoate phb", "from which the", "which the coq10", "the coq10 head", "coq10 head group", "head group is", "group is derived", "derived banh", "banh et al.", "al. 2021", "2021 . because", ". because hpdl", "because hpdl is", "hpdl is a", "is a mitochondrial", "a mitochondrial protein", "protein cytosolic", "cytosolic hpp from", "hpp from tyrosine", "from tyrosine catabolism", "tyrosine catabolism must", "catabolism must either", "must either be", "either be imported", "be imported by", "imported by a", "by a yet", "a yet unknown", "yet unknown transport", "unknown transport mechanism", "transport mechanism or", "mechanism or mitochondrial", "or mitochondrial hpp", "mitochondrial hpp could", "hpp could be", "could be the", "be the product", "the product of", "product of an", "of an unknown", "an unknown mitochondrial", "unknown mitochondrial reaction", "reaction husain", "husain et al.", "al. 2020", "2020 reviewed", "reviewed in staiano", "in staiano et", "staiano et al.", "al. 2023", "2023 . a", ". a polyprenyl", "a polyprenyl diphosphate", "polyprenyl diphosphate synthase", "synthase pdss1", "2 assembles", "assembles the polyisoprenoid", "the polyisoprenoid tail.", "polyisoprenoid tail. next", "next 4", "4 hydroxybenzoate polyprenyltransferase", "polyprenyltransferase coq2", "coq2 catalyzes", "catalyzes the formation", "the formation of", "formation of the", "of the covalent", "the covalent linkage", "covalent linkage between", "linkage between phb", "between phb and", "phb and the", "and the polyisoprenoid", "the polyisoprenoid tail", "polyisoprenoid tail to", "tail to produce", "to produce 4", "produce 4 hydroxy", "4 hydroxy 3", "hydroxy 3 polyprenyl", "3 polyprenyl benzoic", "polyprenyl benzoic acid", "benzoic acid intermediate", "intermediate dhb", "dhb 3", "3 decaprenyl 4", "decaprenyl 4 hydroxybenzoic", "4 hydroxybenzoic acid", "hydroxybenzoic acid in", "acid in humans", "in humans .", "humans . modifications", ". modifications of", "modifications of the", "of the aromatic", "the aromatic ring", "aromatic ring follow", "ring follow and", "follow and involve", "and involve an", "involve an oxidative", "an oxidative decarboxylation", "decarboxylation two", "hydroxylations two", "two o methylations", "methylations one", "one c methylation.", "c methylation. this", "methylation. this series", "this series of", "series of reactions", "reactions which", "which precise order", "precise order is", "order is not", "is not fully", "not fully established", "established especially", "especially regarding the", "regarding the oxidative", "the oxidative decarboxylation", "oxidative decarboxylation step", "step pelosi", "pelosi et al.", "al. 2024", "2024 nicoll", "nicoll et al.", "yield the fully", "the fully substituted", "fully substituted hydroquinone", "hydroquinone ubiquinol", "ubiquinol reviewed", "2023 .


homologs of", ".


homologs of the", "of the core", "the core enzymes", "core enzymes coq3", "coq3 coq4", "coq4 coq5", "coq5 coq6", "coq6 coq7", "coq7 and", "and coq9 have", "coq9 have been", "have been shown", "been shown to", "shown to form", "to form a", "form a membrane", "a membrane localized", "membrane localized multienzyme", "localized multienzyme complex", "complex \\coq", "synthome\\ in", "yeast he", "he et al.", "al. 2014", "2014 . there", ". there is", "there is some", "is some evidence", "some evidence of", "evidence of such", "of such a", "such a complex", "complex called", "called complex q", "q in", "humans floyd", "floyd et al.", "al. 2016", "2016 . a", ". a complex", "a complex was", "complex was reconstituted", "was reconstituted in", "reconstituted in vitro", "in vitro with", "vitro with ancestral", "with ancestral versions", "ancestral versions of", "versions of coq3", "of coq3 7", "coq3 7 and", "7 and coq9", "coq9 and", "and was able", "was able to", "able to convert", "to convert a", "convert a short", "a short chain", "short chain analog", "chain analog of", "analog of dhb", "dhb 4", "3 3", "3 methylbut 2", "methylbut 2 en", "2 en 1", "en 1 yl", "1 yl benzoic", "yl benzoic acid", "acid into", "coq1 nicoll", "2024 . coq8a", ". coq8a and", "coq8a and coq8b", "and coq8b proteins", "coq8b proteins may", "proteins may contribute", "may contribute to", "contribute to the", "to the formation", "the formation and", "formation and functionality", "and functionality of", "functionality of this", "of this complex", "complex as", "as they can", "they can bind", "can bind to", "bind to most", "to most core", "most core enzymes", "enzymes floyd", "and as coq8b", "as coq8b increased", "coq8b increased the", "increased the in", "the in vitro", "in vitro activity", "vitro activity of", "activity of coq6", "of coq6 via", "coq6 via phosphorylation", "via phosphorylation of", "phosphorylation of coq3", "coq3 nicoll", "2024 ..

parts of", "..

parts of coq10", "of coq10 synthesis", "coq10 synthesis may", "synthesis may also", "may also occur", "also occur in", "occur in the", "in the golgi", "the golgi and", "golgi and endoplasmic", "and endoplasmic reticulum", "endoplasmic reticulum membranes", "membranes adding", "adding to the", "to the cellular", "the cellular membrane", "cellular membrane coq10", "membrane coq10 pool.", "coq10 pool. the", "pool. the relevance", "the relevance of", "relevance of such", "of such processes", "such processes seems", "processes seems minor", "minor kal\u00e9n", "kal\u00e9n et al.", "al. 1990", "1990 staiano", "2023 .the precise", ".the precise function", "precise function of", "function of two", "of two other", "two other genes", "genes coq10a", "coq10a and coq10b", "coq10b which", "which appear to", "appear to be", "to be quinone", "be quinone binding", "quinone binding proteins", "proteins is", "is still under", "still under investigation.", "under investigation. most", "investigation. most of", "most of the", "of the time", "time coq10", "coq10 is transported", "is transported out", "transported out of", "out of the", "of the mitochondrion", "the mitochondrion and", "mitochondrion and to", "and to the", "to the plasma", "plasma membrane by", "membrane by isoforms", "by isoforms of", "isoforms of the", "of the stard7", "the stard7 lipid", "stard7 lipid carrier", "carrier reviewed", "reviewed in guile", "in guile et", "guile et al.", "2023 .

coq10 deficiency", "deficiency which", "which can result", "can result from", "result from reduced", "from reduced activity", "reduced activity of", "activity of any", "of any biosynthesis", "any biosynthesis core", "biosynthesis core enzymes", "core enzymes or", "enzymes or the", "or the coq8a", "proteins has", "has significant implications.", "significant implications. it", "implications. it is", "it is associated", "is associated with", "associated with several", "with several inherited", "several inherited metabolic", "inherited metabolic disorders", "disorders the", "the phenotypes of", "phenotypes of which", "of which are", "which are extremely", "are extremely heterogeneous.", "extremely heterogeneous. these", "heterogeneous. these disorders", "these disorders range", "disorders range from", "range from fatal", "from fatal neonatal", "fatal neonatal presentations", "neonatal presentations with", "presentations with multisystem", "with multisystem involvement", "multisystem involvement to", "involvement to adult", "to adult onset", "adult onset isolated", "onset isolated myopathy.", "isolated myopathy. however", "however in", "in many cases", "cases the", "the symptoms can", "symptoms can be", "can be ameliorated", "be ameliorated by", "ameliorated by nutritional", "by nutritional supplementation", "nutritional supplementation with", "supplementation with coq10", "coq10 reviewed", "reviewed in quinzii", "in quinzii et", "quinzii et al.", "al. 2017", "2017 staiano", "the length of the", "length of the polyisoprenoid", "of the polyisoprenoid chain", "the polyisoprenoid chain of", "polyisoprenoid chain of ubiquinone", "of ubiquinone aka", "ubiquinone aka coenzyme", "coenzyme q coq", "coq varies", "varies depending on the", "depending on the species", "on the species involved:", "the species involved: it", "species involved: it is", "involved: it is 6", "it is 6 in", "is 6 in budding", "6 in budding yeast", "budding yeast saccharomyces", "yeast saccharomyces cerevisiae", "cerevisiae coq6", "coq6 and 10", "and 10 in humans", "in humans coq10", "humans coq10 .", "coq10 . most ubiquinone", ". most ubiquinone is", "most ubiquinone is naturally", "ubiquinone is naturally reduced", "is naturally reduced to", "naturally reduced to ubiquinol", "to ubiquinol coq10h2", "ubiquinol coq10h2 in", "humans and", "and this form dominates", "this form dominates in", "form dominates in human", "dominates in human tissues.", "in human tissues. it", "human tissues. it functions", "tissues. it functions as", "it functions as a", "functions as a ubiquitous", "as a ubiquitous coenzyme", "a ubiquitous coenzyme in", "ubiquitous coenzyme in redox", "coenzyme in redox reactions", "redox reactions and", "reactions and has", "and has a central", "has a central role", "a central role in", "central role in the", "role in the electron", "in the electron transport", "the electron transport chain", "electron transport chain of", "transport chain of the", "chain of the inner", "of the inner mitochondrial", "the inner mitochondrial membrane.to", "inner mitochondrial membrane.to shuttle", "mitochondrial membrane.to shuttle electrons", "membrane.to shuttle electrons from", "shuttle electrons from complexes", "electrons from complexes i", "from complexes i and", "complexes i and ii", "i and ii to", "and ii to complex", "ii to complex iii.", "to complex iii. it", "complex iii. it also", "iii. it also acts", "it also acts as", "also acts as a", "acts as a cofactor", "as a cofactor for", "a cofactor for biosynthetic", "cofactor for biosynthetic and", "for biosynthetic and catabolic", "biosynthetic and catabolic reactions", "catabolic reactions detoxifies", "reactions detoxifies damaging", "detoxifies damaging lipid species", "lipid species and", "species and engages", "and engages in cellular", "engages in cellular signaling", "in cellular signaling and", "cellular signaling and oxygen", "signaling and oxygen sensing.", "and oxygen sensing. in", "oxygen sensing. in eukaryotes", "in eukaryotes ubiquinones/ubiquinols", "eukaryotes ubiquinones/ubiquinols are", "ubiquinones/ubiquinols are also found", "are also found in", "also found in other", "found in other membranes", "in other membranes such", "other membranes such as", "membranes such as the", "such as the endoplasmic", "as the endoplasmic reticulum", "endoplasmic reticulum golgi", "reticulum golgi vesicles", "golgi vesicles lysosomes", "lysosomes peroxisomes and", "peroxisomes and the plasma", "and the plasma membrane", "plasma membrane reviewed", "membrane reviewed in", "reviewed in guerra &", "in guerra & pagliarini", "& pagliarini 2023", "pagliarini 2023 .

ubiquinol/ubiquinone", "2023 .

ubiquinol/ubiquinone is synthesized", ".

ubiquinol/ubiquinone is synthesized in", "is synthesized in the", "synthesized in the following", "in the following way.", "the following way. initially", "way. initially mitochondrial", "initially mitochondrial 4", "mitochondrial 4 hydroxyphenylpyruvate dioxygenase", "4 hydroxyphenylpyruvate dioxygenase like", "hydroxyphenylpyruvate dioxygenase like protein", "like protein hpdl", "hpdl processes 4", "4 hydroxphenylpyruvate hpp", "s 4 hydroxymandelate", "4 hydroxymandelate 4", "hydroxymandelate 4 hma", "4 hma . hpdl", "hma . hpdl defects", ". hpdl defects lead", "hpdl defects lead to", "defects lead to coq10", "lead to coq10 deficiency.", "to coq10 deficiency. the", "coq10 deficiency. the hpdl", "deficiency. the hpdl product", "the hpdl product 4", "hpdl product 4 hma", "product 4 hma is", "4 hma is a", "hma is a precursor", "is a precursor for", "a precursor for the", "precursor for the synthesis", "for the synthesis of", "the synthesis of 4", "synthesis of 4 hydroxybenzoate", "4 hydroxybenzoate phb", "phb from", "from which the coq10", "which the coq10 head", "the coq10 head group", "coq10 head group is", "head group is derived", "is derived banh", "derived banh et", "et al. 2021", "al. 2021 .", "2021 . because hpdl", ". because hpdl is", "because hpdl is a", "hpdl is a mitochondrial", "is a mitochondrial protein", "mitochondrial protein cytosolic", "protein cytosolic hpp", "cytosolic hpp from tyrosine", "hpp from tyrosine catabolism", "from tyrosine catabolism must", "tyrosine catabolism must either", "catabolism must either be", "must either be imported", "either be imported by", "be imported by a", "imported by a yet", "by a yet unknown", "a yet unknown transport", "yet unknown transport mechanism", "unknown transport mechanism or", "transport mechanism or mitochondrial", "mechanism or mitochondrial hpp", "or mitochondrial hpp could", "mitochondrial hpp could be", "hpp could be the", "could be the product", "be the product of", "the product of an", "product of an unknown", "of an unknown mitochondrial", "an unknown mitochondrial reaction", "mitochondrial reaction husain", "reaction husain et", "et al. 2020", "2020 reviewed in", "reviewed in staiano et", "in staiano et al.", "et al. 2023", "al. 2023 .", "2023 . a polyprenyl", ". a polyprenyl diphosphate", "a polyprenyl diphosphate synthase", "diphosphate synthase pdss1", "synthase pdss1 2", "pdss1 2 assembles", "2 assembles the", "assembles the polyisoprenoid tail.", "the polyisoprenoid tail. next", "tail. next 4", "next 4 hydroxybenzoate", "hydroxybenzoate polyprenyltransferase coq2", "coq2 catalyzes the", "catalyzes the formation of", "the formation of the", "formation of the covalent", "of the covalent linkage", "the covalent linkage between", "covalent linkage between phb", "linkage between phb and", "between phb and the", "phb and the polyisoprenoid", "and the polyisoprenoid tail", "the polyisoprenoid tail to", "polyisoprenoid tail to produce", "tail to produce 4", "to produce 4 hydroxy", "produce 4 hydroxy 3", "4 hydroxy 3 polyprenyl", "hydroxy 3 polyprenyl benzoic", "3 polyprenyl benzoic acid", "polyprenyl benzoic acid intermediate", "acid intermediate dhb", "dhb 3 decaprenyl", "3 decaprenyl 4 hydroxybenzoic", "decaprenyl 4 hydroxybenzoic acid", "4 hydroxybenzoic acid in", "hydroxybenzoic acid in humans", "acid in humans .", "in humans . modifications", "humans . modifications of", ". modifications of the", "modifications of the aromatic", "of the aromatic ring", "the aromatic ring follow", "aromatic ring follow and", "ring follow and involve", "follow and involve an", "and involve an oxidative", "involve an oxidative decarboxylation", "oxidative decarboxylation two", "decarboxylation two hydroxylations", "two hydroxylations two", "hydroxylations two o", "o methylations one", "methylations one c", "one c methylation. this", "c methylation. this series", "methylation. this series of", "this series of reactions", "of reactions which", "reactions which precise", "which precise order is", "precise order is not", "order is not fully", "is not fully established", "fully established especially", "established especially regarding", "especially regarding the oxidative", "regarding the oxidative decarboxylation", "the oxidative decarboxylation step", "decarboxylation step pelosi", "step pelosi et", "et al. 2024", "2024 nicoll et", "2024 yield", "yield the fully substituted", "the fully substituted hydroquinone", "substituted hydroquinone ubiquinol", "ubiquinol reviewed in", "pagliarini 2023 .


homologs", "2023 .


homologs of the", ".


homologs of the core", "of the core enzymes", "the core enzymes coq3", "enzymes coq3 coq4", "coq7 and coq9", "and coq9 have been", "coq9 have been shown", "have been shown to", "been shown to form", "shown to form a", "to form a membrane", "form a membrane localized", "a membrane localized multienzyme", "membrane localized multienzyme complex", "multienzyme complex \\coq", "complex \\coq synthome\\", "\\coq synthome\\ in", "synthome\\ in yeast", "in yeast he", "yeast he et", "et al. 2014", "al. 2014 .", "2014 . there is", ". there is some", "there is some evidence", "is some evidence of", "some evidence of such", "evidence of such a", "of such a complex", "a complex called", "complex called complex", "complex q in", "q in humans", "in humans floyd", "humans floyd et", "et al. 2016", "al. 2016 .", "2016 . a complex", ". a complex was", "a complex was reconstituted", "complex was reconstituted in", "was reconstituted in vitro", "reconstituted in vitro with", "in vitro with ancestral", "vitro with ancestral versions", "with ancestral versions of", "ancestral versions of coq3", "versions of coq3 7", "of coq3 7 and", "coq3 7 and coq9", "and coq9 and", "coq9 and was", "and was able to", "was able to convert", "able to convert a", "to convert a short", "convert a short chain", "a short chain analog", "short chain analog of", "chain analog of dhb", "of dhb 4", "dhb 4 hydroxy", "hydroxy 3 3", "3 3 methylbut", "3 methylbut 2 en", "methylbut 2 en 1", "2 en 1 yl", "en 1 yl benzoic", "1 yl benzoic acid", "benzoic acid into", "acid into coq1", "into coq1 nicoll", "coq1 nicoll et", "al. 2024 .", "2024 . coq8a and", ". coq8a and coq8b", "coq8a and coq8b proteins", "and coq8b proteins may", "coq8b proteins may contribute", "proteins may contribute to", "may contribute to the", "contribute to the formation", "to the formation and", "the formation and functionality", "formation and functionality of", "and functionality of this", "functionality of this complex", "this complex as", "complex as they", "as they can bind", "they can bind to", "can bind to most", "bind to most core", "to most core enzymes", "core enzymes floyd", "enzymes floyd et", "2016 and", "and as coq8b increased", "as coq8b increased the", "coq8b increased the in", "increased the in vitro", "the in vitro activity", "in vitro activity of", "vitro activity of coq6", "activity of coq6 via", "of coq6 via phosphorylation", "coq6 via phosphorylation of", "via phosphorylation of coq3", "of coq3 nicoll", "coq3 nicoll et", "al. 2024 ..

parts", "2024 ..

parts of coq10", "..

parts of coq10 synthesis", "of coq10 synthesis may", "coq10 synthesis may also", "synthesis may also occur", "may also occur in", "also occur in the", "occur in the golgi", "in the golgi and", "the golgi and endoplasmic", "golgi and endoplasmic reticulum", "and endoplasmic reticulum membranes", "reticulum membranes adding", "membranes adding to", "adding to the cellular", "to the cellular membrane", "the cellular membrane coq10", "cellular membrane coq10 pool.", "membrane coq10 pool. the", "coq10 pool. the relevance", "pool. the relevance of", "the relevance of such", "relevance of such processes", "of such processes seems", "such processes seems minor", "seems minor kal\u00e9n", "minor kal\u00e9n et", "et al. 1990", "1990 staiano et", "al. 2023 .the", "2023 .the precise function", ".the precise function of", "precise function of two", "function of two other", "of two other genes", "other genes coq10a", "genes coq10a and", "and coq10b which", "coq10b which appear", "which appear to be", "appear to be quinone", "to be quinone binding", "be quinone binding proteins", "binding proteins is", "proteins is still", "is still under investigation.", "still under investigation. most", "under investigation. most of", "investigation. most of the", "most of the time", "the time coq10", "time coq10 is", "coq10 is transported out", "is transported out of", "transported out of the", "out of the mitochondrion", "of the mitochondrion and", "the mitochondrion and to", "mitochondrion and to the", "and to the plasma", "to the plasma membrane", "the plasma membrane by", "plasma membrane by isoforms", "membrane by isoforms of", "by isoforms of the", "isoforms of the stard7", "of the stard7 lipid", "the stard7 lipid carrier", "lipid carrier reviewed", "carrier reviewed in", "reviewed in guile et", "in guile et al.", "al. 2023 .

coq10", ".

coq10 deficiency which", "deficiency which can", "which can result from", "can result from reduced", "result from reduced activity", "from reduced activity of", "reduced activity of any", "activity of any biosynthesis", "of any biosynthesis core", "any biosynthesis core enzymes", "biosynthesis core enzymes or", "core enzymes or the", "enzymes or the coq8a", "the coq8a and", "coq8b proteins has", "proteins has significant", "has significant implications. it", "significant implications. it is", "implications. it is associated", "it is associated with", "is associated with several", "associated with several inherited", "with several inherited metabolic", "several inherited metabolic disorders", "metabolic disorders the", "disorders the phenotypes", "the phenotypes of which", "phenotypes of which are", "of which are extremely", "which are extremely heterogeneous.", "are extremely heterogeneous. these", "extremely heterogeneous. these disorders", "heterogeneous. these disorders range", "these disorders range from", "disorders range from fatal", "range from fatal neonatal", "from fatal neonatal presentations", "fatal neonatal presentations with", "neonatal presentations with multisystem", "presentations with multisystem involvement", "with multisystem involvement to", "multisystem involvement to adult", "involvement to adult onset", "to adult onset isolated", "adult onset isolated myopathy.", "onset isolated myopathy. however", "myopathy. however in", "however in many", "many cases the", "cases the symptoms", "the symptoms can be", "symptoms can be ameliorated", "can be ameliorated by", "be ameliorated by nutritional", "ameliorated by nutritional supplementation", "by nutritional supplementation with", "nutritional supplementation with coq10", "with coq10 reviewed", "coq10 reviewed in", "reviewed in quinzii et", "in quinzii et al.", "et al. 2017", "2017 staiano et", "the length of the polyisoprenoid", "length of the polyisoprenoid chain", "of the polyisoprenoid chain of", "the polyisoprenoid chain of ubiquinone", "chain of ubiquinone aka", "of ubiquinone aka coenzyme", "ubiquinone aka coenzyme q", "aka coenzyme q coq", "coq varies depending", "varies depending on the species", "depending on the species involved:", "on the species involved: it", "the species involved: it is", "species involved: it is 6", "involved: it is 6 in", "it is 6 in budding", "is 6 in budding yeast", "in budding yeast saccharomyces", "budding yeast saccharomyces cerevisiae", "saccharomyces cerevisiae coq6", "coq6 and 10 in", "10 in humans coq10", "in humans coq10 .", "humans coq10 . most", "coq10 . most ubiquinone is", ". most ubiquinone is naturally", "most ubiquinone is naturally reduced", "ubiquinone is naturally reduced to", "is naturally reduced to ubiquinol", "reduced to ubiquinol coq10h2", "to ubiquinol coq10h2 in", "ubiquinol coq10h2 in humans", "in humans and", "humans and this", "and this form dominates in", "this form dominates in human", "form dominates in human tissues.", "dominates in human tissues. it", "in human tissues. it functions", "human tissues. it functions as", "tissues. it functions as a", "it functions as a ubiquitous", "functions as a ubiquitous coenzyme", "as a ubiquitous coenzyme in", "a ubiquitous coenzyme in redox", "ubiquitous coenzyme in redox reactions", "in redox reactions and", "redox reactions and has", "reactions and has a", "and has a central role", "has a central role in", "a central role in the", "central role in the electron", "role in the electron transport", "in the electron transport chain", "the electron transport chain of", "electron transport chain of the", "transport chain of the inner", "chain of the inner mitochondrial", "of the inner mitochondrial membrane.to", "the inner mitochondrial membrane.to shuttle", "inner mitochondrial membrane.to shuttle electrons", "mitochondrial membrane.to shuttle electrons from", "membrane.to shuttle electrons from complexes", "shuttle electrons from complexes i", "electrons from complexes i and", "from complexes i and ii", "complexes i and ii to", "i and ii to complex", "and ii to complex iii.", "ii to complex iii. it", "to complex iii. it also", "complex iii. it also acts", "iii. it also acts as", "it also acts as a", "also acts as a cofactor", "acts as a cofactor for", "as a cofactor for biosynthetic", "a cofactor for biosynthetic and", "cofactor for biosynthetic and catabolic", "for biosynthetic and catabolic reactions", "and catabolic reactions detoxifies", "catabolic reactions detoxifies damaging", "reactions detoxifies damaging lipid", "damaging lipid species and", "lipid species and engages", "species and engages in", "and engages in cellular signaling", "engages in cellular signaling and", "in cellular signaling and oxygen", "cellular signaling and oxygen sensing.", "signaling and oxygen sensing. in", "and oxygen sensing. in eukaryotes", "sensing. in eukaryotes ubiquinones/ubiquinols", "in eukaryotes ubiquinones/ubiquinols are", "eukaryotes ubiquinones/ubiquinols are also", "ubiquinones/ubiquinols are also found in", "are also found in other", "also found in other membranes", "found in other membranes such", "in other membranes such as", "other membranes such as the", "membranes such as the endoplasmic", "such as the endoplasmic reticulum", "the endoplasmic reticulum golgi", "endoplasmic reticulum golgi vesicles", "vesicles lysosomes peroxisomes", "lysosomes peroxisomes and the", "peroxisomes and the plasma membrane", "the plasma membrane reviewed", "plasma membrane reviewed in", "membrane reviewed in guerra", "reviewed in guerra & pagliarini", "guerra & pagliarini 2023", "& pagliarini 2023 .

ubiquinol/ubiquinone", "pagliarini 2023 .

ubiquinol/ubiquinone is", "2023 .

ubiquinol/ubiquinone is synthesized in", ".

ubiquinol/ubiquinone is synthesized in the", "is synthesized in the following", "synthesized in the following way.", "in the following way. initially", "following way. initially mitochondrial", "way. initially mitochondrial 4", "initially mitochondrial 4 hydroxyphenylpyruvate", "mitochondrial 4 hydroxyphenylpyruvate dioxygenase like", "4 hydroxyphenylpyruvate dioxygenase like protein", "dioxygenase like protein hpdl", "protein hpdl processes", "hpdl processes 4 hydroxphenylpyruvate", "processes 4 hydroxphenylpyruvate hpp", "hydroxphenylpyruvate hpp hppa", "hpp hppa to", "hppa to s", "to s 4", "4 hydroxymandelate 4 hma", "hydroxymandelate 4 hma .", "4 hma . hpdl defects", "hma . hpdl defects lead", ". hpdl defects lead to", "hpdl defects lead to coq10", "defects lead to coq10 deficiency.", "lead to coq10 deficiency. the", "to coq10 deficiency. the hpdl", "coq10 deficiency. the hpdl product", "deficiency. the hpdl product 4", "the hpdl product 4 hma", "hpdl product 4 hma is", "product 4 hma is a", "4 hma is a precursor", "hma is a precursor for", "is a precursor for the", "a precursor for the synthesis", "precursor for the synthesis of", "for the synthesis of 4", "the synthesis of 4 hydroxybenzoate", "of 4 hydroxybenzoate phb", "phb from which", "from which the coq10 head", "which the coq10 head group", "the coq10 head group is", "coq10 head group is derived", "group is derived banh", "is derived banh et", "derived banh et al.", "banh et al. 2021", "et al. 2021 .", "al. 2021 . because", "2021 . because hpdl is", ". because hpdl is a", "because hpdl is a mitochondrial", "hpdl is a mitochondrial protein", "a mitochondrial protein cytosolic", "mitochondrial protein cytosolic hpp", "protein cytosolic hpp from", "cytosolic hpp from tyrosine catabolism", "hpp from tyrosine catabolism must", "from tyrosine catabolism must either", "tyrosine catabolism must either be", "catabolism must either be imported", "must either be imported by", "either be imported by a", "be imported by a yet", "imported by a yet unknown", "by a yet unknown transport", "a yet unknown transport mechanism", "yet unknown transport mechanism or", "unknown transport mechanism or mitochondrial", "transport mechanism or mitochondrial hpp", "mechanism or mitochondrial hpp could", "or mitochondrial hpp could be", "mitochondrial hpp could be the", "hpp could be the product", "could be the product of", "be the product of an", "the product of an unknown", "product of an unknown mitochondrial", "of an unknown mitochondrial reaction", "unknown mitochondrial reaction husain", "mitochondrial reaction husain et", "reaction husain et al.", "husain et al. 2020", "al. 2020 reviewed", "2020 reviewed in staiano", "reviewed in staiano et al.", "staiano et al. 2023", "et al. 2023 .", "al. 2023 . a", "2023 . a polyprenyl diphosphate", ". a polyprenyl diphosphate synthase", "polyprenyl diphosphate synthase pdss1", "diphosphate synthase pdss1 2", "pdss1 2 assembles the", "2 assembles the polyisoprenoid", "assembles the polyisoprenoid tail. next", "polyisoprenoid tail. next 4", "tail. next 4 hydroxybenzoate", "next 4 hydroxybenzoate polyprenyltransferase", "4 hydroxybenzoate polyprenyltransferase coq2", "polyprenyltransferase coq2 catalyzes", "coq2 catalyzes the formation", "catalyzes the formation of the", "the formation of the covalent", "formation of the covalent linkage", "of the covalent linkage between", "the covalent linkage between phb", "covalent linkage between phb and", "linkage between phb and the", "between phb and the polyisoprenoid", "phb and the polyisoprenoid tail", "and the polyisoprenoid tail to", "the polyisoprenoid tail to produce", "polyisoprenoid tail to produce 4", "tail to produce 4 hydroxy", "to produce 4 hydroxy 3", "produce 4 hydroxy 3 polyprenyl", "4 hydroxy 3 polyprenyl benzoic", "hydroxy 3 polyprenyl benzoic acid", "3 polyprenyl benzoic acid intermediate", "benzoic acid intermediate dhb", "intermediate dhb 3", "dhb 3 decaprenyl 4", "3 decaprenyl 4 hydroxybenzoic acid", "decaprenyl 4 hydroxybenzoic acid in", "4 hydroxybenzoic acid in humans", "hydroxybenzoic acid in humans .", "acid in humans . modifications", "in humans . modifications of", "humans . modifications of the", ". modifications of the aromatic", "modifications of the aromatic ring", "of the aromatic ring follow", "the aromatic ring follow and", "aromatic ring follow and involve", "ring follow and involve an", "follow and involve an oxidative", "and involve an oxidative decarboxylation", "an oxidative decarboxylation two", "oxidative decarboxylation two hydroxylations", "two hydroxylations two o", "hydroxylations two o methylations", "two o methylations one", "o methylations one c", "methylations one c methylation.", "one c methylation. this series", "c methylation. this series of", "methylation. this series of reactions", "series of reactions which", "of reactions which precise", "reactions which precise order", "which precise order is not", "precise order is not fully", "order is not fully established", "not fully established especially", "fully established especially regarding", "established especially regarding the", "especially regarding the oxidative decarboxylation", "regarding the oxidative decarboxylation step", "oxidative decarboxylation step pelosi", "decarboxylation step pelosi et", "step pelosi et al.", "pelosi et al. 2024", "al. 2024 nicoll", "2024 nicoll et al.", "nicoll et al. 2024", "2024 yield the", "yield the fully substituted hydroquinone", "fully substituted hydroquinone ubiquinol", "hydroquinone ubiquinol reviewed", "ubiquinol reviewed in guerra", "& pagliarini 2023 .


homologs", "pagliarini 2023 .


homologs of", "2023 .


homologs of the core", ".


homologs of the core enzymes", "of the core enzymes coq3", "core enzymes coq3 coq4", "coq3 coq4 coq5", "coq4 coq5 coq6", "coq5 coq6 coq7", "coq6 coq7 and", "coq7 and coq9 have", "and coq9 have been shown", "coq9 have been shown to", "have been shown to form", "been shown to form a", "shown to form a membrane", "to form a membrane localized", "form a membrane localized multienzyme", "a membrane localized multienzyme complex", "localized multienzyme complex \\coq", "multienzyme complex \\coq synthome\\", "\\coq synthome\\ in yeast", "in yeast he et", "yeast he et al.", "he et al. 2014", "et al. 2014 .", "al. 2014 . there", "2014 . there is some", ". there is some evidence", "there is some evidence of", "is some evidence of such", "some evidence of such a", "evidence of such a complex", "such a complex called", "a complex called complex", "complex called complex q", "called complex q in", "complex q in humans", "in humans floyd et", "humans floyd et al.", "floyd et al. 2016", "et al. 2016 .", "al. 2016 . a", "2016 . a complex was", ". a complex was reconstituted", "a complex was reconstituted in", "complex was reconstituted in vitro", "was reconstituted in vitro with", "reconstituted in vitro with ancestral", "in vitro with ancestral versions", "vitro with ancestral versions of", "with ancestral versions of coq3", "ancestral versions of coq3 7", "versions of coq3 7 and", "of coq3 7 and coq9", "7 and coq9 and", "and coq9 and was", "coq9 and was able", "and was able to convert", "was able to convert a", "able to convert a short", "to convert a short chain", "convert a short chain analog", "a short chain analog of", "short chain analog of dhb", "analog of dhb 4", "of dhb 4 hydroxy", "dhb 4 hydroxy 3", "4 hydroxy 3 3", "hydroxy 3 3 methylbut", "3 3 methylbut 2", "3 methylbut 2 en 1", "methylbut 2 en 1 yl", "2 en 1 yl benzoic", "en 1 yl benzoic acid", "yl benzoic acid into", "benzoic acid into coq1", "into coq1 nicoll et", "coq1 nicoll et al.", "et al. 2024 .", "al. 2024 . coq8a", "2024 . coq8a and coq8b", ". coq8a and coq8b proteins", "coq8a and coq8b proteins may", "and coq8b proteins may contribute", "coq8b proteins may contribute to", "proteins may contribute to the", "may contribute to the formation", "contribute to the formation and", "to the formation and functionality", "the formation and functionality of", "formation and functionality of this", "and functionality of this complex", "of this complex as", "this complex as they", "complex as they can", "as they can bind to", "they can bind to most", "can bind to most core", "bind to most core enzymes", "most core enzymes floyd", "core enzymes floyd et", "enzymes floyd et al.", "2016 and as", "and as coq8b increased the", "as coq8b increased the in", "coq8b increased the in vitro", "increased the in vitro activity", "the in vitro activity of", "in vitro activity of coq6", "vitro activity of coq6 via", "activity of coq6 via phosphorylation", "of coq6 via phosphorylation of", "coq6 via phosphorylation of coq3", "phosphorylation of coq3 nicoll", "of coq3 nicoll et", "coq3 nicoll et al.", "et al. 2024 ..

parts", "al. 2024 ..

parts of", "2024 ..

parts of coq10 synthesis", "..

parts of coq10 synthesis may", "of coq10 synthesis may also", "coq10 synthesis may also occur", "synthesis may also occur in", "may also occur in the", "also occur in the golgi", "occur in the golgi and", "in the golgi and endoplasmic", "the golgi and endoplasmic reticulum", "golgi and endoplasmic reticulum membranes", "endoplasmic reticulum membranes adding", "reticulum membranes adding to", "membranes adding to the", "adding to the cellular membrane", "to the cellular membrane coq10", "the cellular membrane coq10 pool.", "cellular membrane coq10 pool. the", "membrane coq10 pool. the relevance", "coq10 pool. the relevance of", "pool. the relevance of such", "the relevance of such processes", "relevance of such processes seems", "of such processes seems minor", "processes seems minor kal\u00e9n", "seems minor kal\u00e9n et", "minor kal\u00e9n et al.", "kal\u00e9n et al. 1990", "al. 1990 staiano", "1990 staiano et al.", "et al. 2023 .the", "al. 2023 .the precise", "2023 .the precise function of", ".the precise function of two", "precise function of two other", "function of two other genes", "two other genes coq10a", "other genes coq10a and", "genes coq10a and coq10b", "coq10a and coq10b which", "and coq10b which appear", "coq10b which appear to", "which appear to be quinone", "appear to be quinone binding", "to be quinone binding proteins", "quinone binding proteins is", "binding proteins is still", "proteins is still under", "is still under investigation. most", "still under investigation. most of", "under investigation. most of the", "investigation. most of the time", "of the time coq10", "the time coq10 is", "time coq10 is transported", "coq10 is transported out of", "is transported out of the", "transported out of the mitochondrion", "out of the mitochondrion and", "of the mitochondrion and to", "the mitochondrion and to the", "mitochondrion and to the plasma", "and to the plasma membrane", "to the plasma membrane by", "the plasma membrane by isoforms", "plasma membrane by isoforms of", "membrane by isoforms of the", "by isoforms of the stard7", "isoforms of the stard7 lipid", "of the stard7 lipid carrier", "stard7 lipid carrier reviewed", "lipid carrier reviewed in", "carrier reviewed in guile", "reviewed in guile et al.", "guile et al. 2023", "et al. 2023 .

coq10", "al. 2023 .

coq10 deficiency", "2023 .

coq10 deficiency which", ".

coq10 deficiency which can", "deficiency which can result", "which can result from reduced", "can result from reduced activity", "result from reduced activity of", "from reduced activity of any", "reduced activity of any biosynthesis", "activity of any biosynthesis core", "of any biosynthesis core enzymes", "any biosynthesis core enzymes or", "biosynthesis core enzymes or the", "core enzymes or the coq8a", "or the coq8a and", "the coq8a and coq8b", "and coq8b proteins has", "coq8b proteins has significant", "proteins has significant implications.", "has significant implications. it is", "significant implications. it is associated", "implications. it is associated with", "it is associated with several", "is associated with several inherited", "associated with several inherited metabolic", "with several inherited metabolic disorders", "inherited metabolic disorders the", "metabolic disorders the phenotypes", "disorders the phenotypes of", "the phenotypes of which are", "phenotypes of which are extremely", "of which are extremely heterogeneous.", "which are extremely heterogeneous. these", "are extremely heterogeneous. these disorders", "extremely heterogeneous. these disorders range", "heterogeneous. these disorders range from", "these disorders range from fatal", "disorders range from fatal neonatal", "range from fatal neonatal presentations", "from fatal neonatal presentations with", "fatal neonatal presentations with multisystem", "neonatal presentations with multisystem involvement", "presentations with multisystem involvement to", "with multisystem involvement to adult", "multisystem involvement to adult onset", "involvement to adult onset isolated", "to adult onset isolated myopathy.", "adult onset isolated myopathy. however", "isolated myopathy. however in", "myopathy. however in many", "however in many cases", "in many cases the", "many cases the symptoms", "cases the symptoms can", "the symptoms can be ameliorated", "symptoms can be ameliorated by", "can be ameliorated by nutritional", "be ameliorated by nutritional supplementation", "ameliorated by nutritional supplementation with", "by nutritional supplementation with coq10", "supplementation with coq10 reviewed", "with coq10 reviewed in", "coq10 reviewed in quinzii", "reviewed in quinzii et al.", "quinzii et al. 2017", "al. 2017 staiano", "2017 staiano et al." ] }, { "record_id": "GLY_000594_1_883", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2151209", "r hsa", "hsa 2151209", "r hsa 2151209" ] }, { "record_id": "GLY_000594_1_883", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of ppargc1a", "pgc 1alpha", "by phosphorylation", "activation of ppargc1a", "ppargc1a pgc", "1alpha by", "of ppargc1a pgc", "ppargc1a pgc 1alpha", "pgc 1alpha by", "1alpha by phosphorylation", "activation of ppargc1a pgc", "of ppargc1a pgc 1alpha", "pgc 1alpha by phosphorylation", "the transcriptional", "transcriptional coactivator", "coactivator ppargc1a", "one of", "of the", "the master", "master regulators", "regulators of", "of mitochondrial", "mitochondrial biogenesis", "is activated", "activated by", "by phosphorylation.", "phosphorylation. energy", "energy depletion", "depletion causes", "causes a", "a reduction", "reduction in", "in atp", "atp and", "and an", "an increase", "increase in", "in amp", "amp which", "which activates", "activates ampk.", "ampk. ampk", "ampk in", "in turn", "turn phosphorylates", "phosphorylates ppargc1a.", "ppargc1a. likewise", "p38 mapk", "mapk is", "by muscle", "muscle contraction", "possibly via", "via calcium", "calcium and", "and camkii", "and phosphorylates", "ppargc1a. ppargc1a", "ppargc1a does", "does not", "not bind", "bind dna", "dna directly", "but rather", "rather interacts", "interacts with", "with other", "other transcription", "transcription factors.", "factors. deacetylation", "deacetylation of", "ppargc1a by", "by sirt1", "sirt1 appears", "appears to", "to follow", "follow phosphorylation", "phosphorylation however", "however the", "the role", "role of", "of deacetylation", "deacetylation is", "is unresolved", "canto et", "et al.", "al. 2009", "gurd et", "al. 2011", "philp et", "the transcriptional coactivator", "transcriptional coactivator ppargc1a", "one of the", "of the master", "the master regulators", "master regulators of", "regulators of mitochondrial", "of mitochondrial biogenesis", "biogenesis is", "is activated by", "activated by phosphorylation.", "by phosphorylation. energy", "phosphorylation. energy depletion", "energy depletion causes", "depletion causes a", "causes a reduction", "a reduction in", "reduction in atp", "in atp and", "atp and an", "and an increase", "an increase in", "increase in amp", "in amp which", "amp which activates", "which activates ampk.", "activates ampk. ampk", "ampk. ampk in", "ampk in turn", "in turn phosphorylates", "turn phosphorylates ppargc1a.", "phosphorylates ppargc1a. likewise", "likewise p38", "p38 mapk is", "mapk is activated", "activated by muscle", "by muscle contraction", "contraction possibly", "possibly via calcium", "via calcium and", "calcium and camkii", "camkii and", "and phosphorylates ppargc1a.", "phosphorylates ppargc1a. ppargc1a", "ppargc1a. ppargc1a does", "ppargc1a does not", "does not bind", "not bind dna", "bind dna directly", "directly but", "but rather interacts", "rather interacts with", "interacts with other", "with other transcription", "other transcription factors.", "transcription factors. deacetylation", "factors. deacetylation of", "deacetylation of ppargc1a", "of ppargc1a by", "ppargc1a by sirt1", "by sirt1 appears", "sirt1 appears to", "appears to follow", "to follow phosphorylation", "follow phosphorylation however", "phosphorylation however the", "however the role", "the role of", "role of deacetylation", "of deacetylation is", "deacetylation is unresolved", "unresolved canto", "canto et al.", "et al. 2009", "2009 gurd", "gurd et al.", "et al. 2011", "2011 philp", "philp et al.", "the transcriptional coactivator ppargc1a", "coactivator ppargc1a pgc", "1alpha one", "one of the master", "of the master regulators", "the master regulators of", "master regulators of mitochondrial", "regulators of mitochondrial biogenesis", "mitochondrial biogenesis is", "biogenesis is activated", "is activated by phosphorylation.", "activated by phosphorylation. energy", "by phosphorylation. energy depletion", "phosphorylation. energy depletion causes", "energy depletion causes a", "depletion causes a reduction", "causes a reduction in", "a reduction in atp", "reduction in atp and", "in atp and an", "atp and an increase", "and an increase in", "an increase in amp", "increase in amp which", "in amp which activates", "amp which activates ampk.", "which activates ampk. ampk", "activates ampk. ampk in", "ampk. ampk in turn", "ampk in turn phosphorylates", "in turn phosphorylates ppargc1a.", 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follow phosphorylation", "to follow phosphorylation however", "follow phosphorylation however the", "phosphorylation however the role", "however the role of", "the role of deacetylation", "role of deacetylation is", "of deacetylation is unresolved", "is unresolved canto", "unresolved canto et", "canto et al. 2009", "al. 2009 gurd", "2009 gurd et", "gurd et al. 2011", "al. 2011 philp", "2011 philp et", "philp et al. 2011", "transcriptional coactivator ppargc1a pgc", "coactivator ppargc1a pgc 1alpha", "pgc 1alpha one", "1alpha one of", "one of the master regulators", "of the master regulators of", "the master regulators of mitochondrial", "master regulators of mitochondrial biogenesis", "of mitochondrial biogenesis is", "mitochondrial biogenesis is activated", "biogenesis is activated by", "is activated by phosphorylation. energy", "activated by phosphorylation. energy depletion", "by phosphorylation. energy depletion causes", "phosphorylation. energy depletion causes a", "energy depletion causes a reduction", "depletion causes a reduction in", "causes a reduction in atp", "a reduction in atp and", "reduction in atp and an", "in atp and an increase", "atp and an increase in", "and an increase in amp", "an increase in amp which", "increase in amp which activates", "in amp which activates ampk.", "amp which activates ampk. ampk", "which activates ampk. ampk in", "activates ampk. ampk in turn", "ampk. ampk in turn phosphorylates", "ampk in turn phosphorylates ppargc1a.", "in turn phosphorylates ppargc1a. likewise", "phosphorylates ppargc1a. likewise p38", "ppargc1a. likewise p38 mapk", "likewise p38 mapk is", "p38 mapk is activated by", "mapk is activated by muscle", "is activated by muscle contraction", "by muscle contraction possibly", "muscle contraction possibly via", "contraction possibly via calcium", "possibly via calcium and camkii", "calcium and camkii and", "and camkii and phosphorylates", "camkii and phosphorylates ppargc1a.", "and phosphorylates ppargc1a. ppargc1a does", "phosphorylates ppargc1a. ppargc1a does not", "ppargc1a. ppargc1a does not bind", "ppargc1a does not bind dna", "does not bind dna directly", "bind dna directly but", "dna directly but rather", "directly but rather interacts", "but rather interacts with other", "rather interacts with other transcription", "interacts with other transcription factors.", "with other transcription factors. deacetylation", "other transcription factors. deacetylation of", "transcription factors. deacetylation of ppargc1a", "factors. deacetylation of ppargc1a by", "deacetylation of ppargc1a by sirt1", "of ppargc1a by sirt1 appears", "ppargc1a by sirt1 appears to", "by sirt1 appears to follow", "sirt1 appears to follow phosphorylation", "appears to follow phosphorylation however", "to follow phosphorylation however the", "follow phosphorylation however the role", "phosphorylation however the role of", "however the role of deacetylation", "the role of deacetylation is", "role of deacetylation is unresolved", "deacetylation is unresolved canto", "is unresolved canto et", "unresolved canto et al.", "et al. 2009 gurd", "al. 2009 gurd et", "2009 gurd et al.", "et al. 2011 philp", "al. 2011 philp et", "2011 philp et al." ] }, { "record_id": "GLY_000594_1_884", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2160456", "r hsa", "hsa 2160456", "r hsa 2160456" ] }, { "record_id": "GLY_000594_1_884", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phenylalanine hydroxylase", "normally catalyzes", "catalyzes the", "the conversion", "conversion of", "of phenylalanine", "phenylalanine to", "to tyrosine.", "tyrosine. in", "in the", "the absence", "absence of", "of functional", "functional pah", "phenylalanine accumulates", "accumulates to", "to high", "high levels", "levels in", "the blood", "blood and", "and is", "is converted", "converted to", "to phenylpyruvate", "phenylpyruvate and", "and phenyllactate", "clemens et", "et al.", "al. 1990", "langenbeck et", "al. 1992", "mitchell et", "al. 2011", "2011 .", ". the", "the extent", "extent of", "of these", "these conversions", "conversions is", "is modulated", "modulated by", "by genetic", "genetic factors", "factors distinct", "distinct from", "from pah", "as siblings", "siblings with", "with the", "the identical", "identical pah", "pah defect", "defect can", "can produce", "produce different", "different amounts", "amounts of", "of them", "treacy et", "al. 1996", "1996 .

both", ".

both l", "l amino", "amino acid", "acid oxidase", "boulland et", "al. 2004", "and kynurenine", "oxoglutarate transaminase", "transaminase 3", "han et", "can catalyze", "catalyze the", "and lactate", "lactate dehydrogenase", "dehydrogenase can", "of the", "the latter", "latter molecule", "molecule to", "to phenyllactate", "meister 1950", "in reactions", "reactions not", "not annotated", "annotated here.", "hydroxylase pah", "pah normally", "normally catalyzes the", "catalyzes the conversion", "the conversion of", "conversion of phenylalanine", "of phenylalanine to", "phenylalanine to tyrosine.", "to tyrosine. in", "tyrosine. in the", "in the absence", "the absence of", "absence of functional", "of functional pah", "pah phenylalanine", "phenylalanine accumulates to", "accumulates to high", "to high levels", "high levels in", "levels in the", "in the blood", "the blood and", "blood and is", "and is converted", "is converted to", "converted to phenylpyruvate", "to phenylpyruvate and", "phenylpyruvate and phenyllactate", "phenyllactate clemens", "clemens et al.", "et al. 1990", "1990 langenbeck", "langenbeck et al.", "et al. 1992", "1992 mitchell", "mitchell et al.", "et al. 2011", "al. 2011 .", "2011 . the", ". the extent", "the extent of", "extent of these", "of these conversions", "these conversions is", "conversions is modulated", "is modulated by", "modulated by genetic", "by genetic factors", "genetic factors distinct", "factors distinct from", "distinct from pah", "pah as", "as siblings with", "siblings with the", "with the identical", "the identical pah", "identical pah defect", "pah defect can", "defect can produce", "can produce different", "produce different amounts", "different amounts of", "amounts of them", "them treacy", "treacy et al.", "et al. 1996", "al. 1996 .

both", "1996 .

both l", ".

both l amino", "l amino acid", "amino acid oxidase", "oxidase boulland", "boulland et al.", "et al. 2004", "2004 and", "kynurenine oxoglutarate", "oxoglutarate transaminase 3", "3 han", "han et al.", "2004 can", "can catalyze the", "catalyze the conversion", "phenylalanine to phenylpyruvate", "phenylpyruvate and lactate", "and lactate dehydrogenase", "lactate dehydrogenase can", "dehydrogenase can catalyze", "conversion of the", "of the latter", "the latter molecule", "latter molecule to", "molecule to phenyllactate", "phenyllactate meister", "in reactions not", "reactions not annotated", "not annotated here.", "phenylalanine hydroxylase pah", "pah normally catalyzes", "normally catalyzes the conversion", "catalyzes the conversion of", "the conversion of phenylalanine", "conversion of phenylalanine to", "of phenylalanine to tyrosine.", "phenylalanine to tyrosine. in", "to tyrosine. in the", "tyrosine. in the absence", "in the absence of", "the absence of functional", "absence of functional pah", "functional pah phenylalanine", "pah phenylalanine accumulates", "phenylalanine accumulates to high", "accumulates to high levels", "to high levels in", "high levels in the", "levels in the blood", "in the blood and", "the blood and is", "blood and is converted", "and is converted to", "is converted to phenylpyruvate", "converted to phenylpyruvate and", "to phenylpyruvate and phenyllactate", "and phenyllactate clemens", "phenyllactate clemens et", "clemens et al. 1990", "al. 1990 langenbeck", "1990 langenbeck et", "langenbeck et al. 1992", "al. 1992 mitchell", "1992 mitchell et", "mitchell et al. 2011", "et al. 2011 .", "al. 2011 . the", "2011 . the extent", ". the extent of", "the extent of these", "extent of these conversions", "of these conversions is", "these conversions is modulated", "conversions is modulated by", "is modulated by genetic", "modulated by genetic factors", "by genetic factors distinct", "genetic factors distinct from", "factors distinct from pah", "from pah as", "pah as siblings", "as siblings with the", "siblings with the identical", "with the identical pah", "the identical pah defect", "identical pah defect can", "pah defect can produce", "defect can produce different", "can produce different amounts", "produce different amounts of", "different amounts of them", "of them treacy", "them treacy et", "treacy et al. 1996", "et al. 1996 .

both", "al. 1996 .

both l", "1996 .

both l amino", ".

both l amino acid", "l amino acid oxidase", "acid oxidase boulland", "oxidase boulland et", "boulland et al. 2004", "al. 2004 and", "2004 and kynurenine", "and kynurenine oxoglutarate", "kynurenine oxoglutarate transaminase", "transaminase 3 han", "3 han et", "han et al. 2004", "al. 2004 can", "2004 can catalyze", "can catalyze the conversion", "catalyze the conversion of", "of phenylalanine to phenylpyruvate", "phenylalanine to phenylpyruvate and", "to phenylpyruvate and lactate", "phenylpyruvate and lactate dehydrogenase", "and lactate dehydrogenase can", "lactate dehydrogenase can catalyze", "dehydrogenase can catalyze the", "the conversion of the", "conversion of the latter", "of the latter molecule", "the latter molecule to", "latter molecule to phenyllactate", "to phenyllactate meister", "phenyllactate meister 1950", "1950 in", "in reactions not annotated", "reactions not annotated here.", "hydroxylase pah normally", "pah normally catalyzes the", "normally catalyzes the conversion of", "catalyzes the conversion of phenylalanine", "the conversion of phenylalanine to", "conversion of phenylalanine to tyrosine.", "of phenylalanine to tyrosine. in", "phenylalanine to tyrosine. in the", "to tyrosine. in the absence", "tyrosine. in the absence of", "in the absence of functional", "the absence of functional pah", "of functional pah phenylalanine", "functional pah phenylalanine accumulates", "pah phenylalanine accumulates to", "phenylalanine accumulates to high levels", "accumulates to high levels in", "to high levels in the", "high levels in the blood", "levels in the blood and", "in the blood and is", "the blood and is converted", "blood and is converted to", "and is converted to phenylpyruvate", "is converted to phenylpyruvate and", "converted to phenylpyruvate and phenyllactate", "phenylpyruvate and phenyllactate clemens", "and phenyllactate clemens et", "phenyllactate clemens et al.", "et al. 1990 langenbeck", "al. 1990 langenbeck et", "1990 langenbeck et al.", "et al. 1992 mitchell", "al. 1992 mitchell et", "1992 mitchell et al.", "mitchell et al. 2011 .", "et al. 2011 . the", "al. 2011 . the extent", "2011 . the extent of", ". the extent of these", "the extent of these conversions", "extent of these conversions is", "of these conversions is modulated", "these conversions is modulated by", "conversions is modulated by genetic", "is modulated by genetic factors", "modulated by genetic factors distinct", "by genetic factors distinct from", "genetic factors distinct from pah", "distinct from pah as", "from pah as siblings", "pah as siblings with", "as siblings with the identical", "siblings with the identical pah", "with the identical pah defect", "the identical pah defect can", "identical pah defect can produce", "pah defect can produce different", "defect can produce different amounts", "can produce different amounts of", "produce different amounts of them", "amounts of them treacy", "of them treacy et", "them treacy et al.", "treacy et al. 1996 .

both", "et al. 1996 .

both l", "al. 1996 .

both l amino", "1996 .

both l amino acid", ".

both l amino acid oxidase", "amino acid oxidase boulland", "acid oxidase boulland et", "oxidase boulland et al.", "et al. 2004 and", "al. 2004 and kynurenine", "and kynurenine oxoglutarate transaminase", "kynurenine oxoglutarate transaminase 3", "oxoglutarate transaminase 3 han", "transaminase 3 han et", "3 han et al.", "et al. 2004 can", "al. 2004 can catalyze", "2004 can catalyze the", "can catalyze the conversion of", "catalyze the conversion of phenylalanine", "conversion of phenylalanine to phenylpyruvate", "of phenylalanine to phenylpyruvate and", "phenylalanine to phenylpyruvate and lactate", "to phenylpyruvate and lactate dehydrogenase", "phenylpyruvate and lactate dehydrogenase can", "and lactate dehydrogenase can catalyze", "lactate dehydrogenase can catalyze the", "dehydrogenase can catalyze the conversion", "catalyze the conversion of the", "the conversion of the latter", "conversion of the latter molecule", "of the latter molecule to", "the latter molecule to phenyllactate", "molecule to phenyllactate meister", "to phenyllactate meister 1950", "meister 1950 in", "1950 in reactions", "in reactions not annotated here." ] }, { "record_id": "GLY_000594_1_885", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2160916", "r hsa", "hsa 2160916", "r hsa 2160916" ] }, { "record_id": "GLY_000594_1_885", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hyaluronan uptake", "uptake and", "and degradation", "hyaluronan uptake and", "uptake and degradation", "hyaluronan uptake and degradation", "turnover can", "can occur", "occur locally", "locally at", "at the", "the tissue", "tissue of", "of origin", "where it", "it is", "is taken", "taken up", "up by", "by cells", "cells to", "to be", "be degraded", "or released", "released into", "into the", "the lymphatic", "lymphatic and", "and vascular", "vascular systems", "it can", "can be", "be eliminated", "eliminated by", "by the", "the liver", "liver and", "and kidneys.", "kidneys. uptake", "uptake of", "of ha", "ha into", "into cells", "cells for", "for degradation", "degradation involves", "involves receptor", "receptor mediated", "mediated processes.", "processes. once", "once ha", "ha enters", "enters lysosomes", "the acidic", "acidic conditions", "conditions favour", "favour hyaluronidases", "hyaluronidases to", "to cleave", "cleave it", "it into", "into small", "small oligosaccharides", "the most", "most common", "common size", "size being", "being a", "a tetrasaccharide.", "tetrasaccharide. beta", "beta glucuronidases", "glucuronidases participate", "participate in", "in degrading", "degrading the", "the small", "oligosaccharides in", "in the", "the lysosome.", "lysosome. ultimately", "ha is", "is degraded", "degraded into", "into its", "its constituent", "constituent sugars", "glucuronic acid", "acid and", "and n", "n acetylglucosamine", "which can", "be used", "used to", "to reform", "reform many", "many glycosaminoglycans", "when released", "released from", "from the", "the lysosome.
a", "lysosome.
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receptor mediated", "degradation involves receptor mediated processes.", "involves receptor mediated processes. once", "receptor mediated processes. once ha", "mediated processes. once ha enters", "processes. once ha enters lysosomes", "ha enters lysosomes the", "enters lysosomes the acidic", "lysosomes the acidic conditions", "the acidic conditions favour hyaluronidases", "acidic conditions favour hyaluronidases to", "conditions favour hyaluronidases to cleave", "favour hyaluronidases to cleave it", "hyaluronidases to cleave it into", "to cleave it into small", "cleave it into small oligosaccharides", "into small oligosaccharides the", "small oligosaccharides the most", "oligosaccharides the most common", "the most common size being", "most common size being a", "common size being a tetrasaccharide.", "size being a tetrasaccharide. beta", "being a tetrasaccharide. beta glucuronidases", "a tetrasaccharide. beta glucuronidases participate", "tetrasaccharide. beta glucuronidases participate in", "beta glucuronidases participate in degrading", "glucuronidases participate in degrading the", "participate in degrading the small", "in degrading the small oligosaccharides", "degrading the small oligosaccharides in", "the small oligosaccharides in the", "small oligosaccharides in the lysosome.", "oligosaccharides in the lysosome. ultimately", "the lysosome. ultimately ha", "lysosome. ultimately ha is", "ultimately ha is degraded", "ha is degraded into its", "is degraded into its constituent", "degraded into its constituent sugars", "its constituent sugars glucuronic", "constituent sugars glucuronic acid", "sugars glucuronic acid and", "glucuronic acid and n acetylglucosamine", "and n acetylglucosamine which", "n acetylglucosamine which can", "acetylglucosamine which can be", "which can be used to", "can be used to reform", "be used to reform many", "used to reform many glycosaminoglycans", "reform many glycosaminoglycans gags", "glycosaminoglycans gags when", "gags when released from", "when released from the lysosome.
a", "released from the lysosome.
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a third of the", "lysosome.
a third of the total", "third of the total ha", "of the total ha content", "the total ha content in", "total ha content in humans", "ha content in humans is", "content in humans is turned", "in humans is turned over", "humans is turned over daily", "is turned over daily and", "turned over daily and it", "over daily and it has", "daily and it has a", "and it has a short", "it has a short half", "has a short half life", "a short half life of", "short half life of minutes", "half life of minutes in", "life of minutes in circulation", "of minutes in circulation up", "minutes in circulation up to", "in circulation up to days", "circulation up to days in", "up to days in many", "to days in many tissues.", "days in many tissues. the", "in many tissues. the reasons", "many tissues. the reasons why", "tissues. the reasons why the", "the reasons why the body", "reasons why the body eliminates", "why the body eliminates ha", "the body eliminates ha so", "body eliminates ha so rapidly", "eliminates ha so rapidly are", "ha so rapidly are unknown", "so rapidly are unknown but", "rapidly are unknown but one", "are unknown but one possible", "unknown but one possible explanation", "but one possible explanation could", "one possible explanation could be", "possible explanation could be ha's", "explanation could be ha's role", "could be ha's role as", "be ha's role as a", "ha's role as a reactive", "role as a reactive oxygen", "as a reactive oxygen species", "reactive oxygen species ros", "species ros scavenger.", "ros scavenger. removing these", "scavenger. removing these toxic compounds", "removing these toxic compounds could", "these toxic compounds could explain", "toxic compounds could explain the", "compounds could explain the rapid", "could explain the rapid elimination", "explain the rapid elimination of", "the rapid elimination of ha", "elimination of ha lepperdinger", "of ha lepperdinger et", "ha lepperdinger et al.", "et al. 2004 menzel", "al. 2004 menzel &", "2004 menzel & farr", "& farr 1998 erickson", "farr 1998 erickson &", "1998 erickson & stern", "& stern 2012 stern", "stern 2012 stern 2003", "2012 stern 2003 ." ] }, { "record_id": "GLY_000594_1_886", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2173789", "r hsa", "hsa 2173789", "r hsa 2173789" ] }, { "record_id": "GLY_000594_1_886", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tgf beta", "beta receptor", "receptor signaling", "signaling activates", "activates smads", "tgf beta receptor", "beta receptor signaling", "receptor signaling activates", "signaling activates smads", "tgf beta receptor signaling", "beta receptor signaling activates", "receptor signaling activates smads", "tgf beta receptor signaling activates", "beta receptor signaling activates smads", "binding of", "of transforming", "transforming growth", "growth factor", "factor beta", "beta 1", "i.e. tgfb1", "to tgf", "receptor type", "type 2", "activates tgf", "signaling cascade.", "cascade. tgfb1", "tgfb1 is", "is posttranslationally", "posttranslationally processed", "processed by", "by furin", "dubois et", "et al.", "al. 1995", "to form", "form a", "a homodimer", "homodimer and", "and secreted", "secreted to", "to the", "the extracellular", "extracellular space", "space as", "as part", "part of", "of the", "the large", "large latent", "latent complex", "llc .", ". after", "after the", "the llc", "llc disassembles", "disassembles in", "in the", "dimeric tgfb1", "tgfb1 becomes", "becomes capable", "capable of", "of binding", "binding to", "to tgfbr2", "annes et", "al. 2003", "keski oja", "oja et", "al. 2004", "2004 .", ". formation", "formation of", "of tgfb1:tgfbr2", "tgfb1:tgfbr2 complex", "complex creates", "creates a", "a binding", "binding pocket", "pocket for", "for tgf", "type 1", "and tgfbr1", "tgfbr1 is", "is recruited", "recruited to", "the complex", "complex by", "by binding", "to both", "both tgfb1", "tgfb1 and", "and tgfbr2.", "tgfbr2. this", "this results", "results in", "in an", "an active", "active heterotetrameric", "heterotetrameric tgf", "receptor complex", "complex that", "that consists", "consists of", "of tgfb1", "tgfb1 homodimer", "homodimer bound", "bound to", "to two", "two heterodimers", "heterodimers of", "of tgfbr1", "tgfbr1 and", "and tgfbr2", "wrana et", "al. 1992", "moustakas et", "al. 1993", "franzen et", "1993 .", ". tgf", "beta signaling", "signaling can", "can also", "also occur", "occur through", "through a", "a single", "single heterodimer", "heterodimer of", "although with", "with decreased", "decreased efficiency", "huang et", "al. 2011", "2011 .", ". tgfbr1", "tgfbr2 interact", "interact through", "through their", "their extracellular", "extracellular domains", "which brings", "brings their", "their cytoplasmic", "cytoplasmic domains", "domains together.", "together. ligand", "ligand binding", "to extracellular", "extracellular receptor", "receptor domains", "domains is", "is cooperative", "but no", "no conformational", "conformational change", "change is", "is seen", "seen from", "from crystal", "crystal structures", "structures of", "of either", "either tgfb1", "or tgfb3", "tgfb3 bound", "bound heterotetrameric", "heterotetrameric receptor", "receptor complexes", "groppe et", "al. 2008", "radaev et", "al. 2010", "2010 .

activation", ".

activation of", "tgfbr1 by", "by tgfbr2", "tgfbr2 in", "the absence", "absence of", "of ligand", "ligand is", "is prevented", "prevented by", "by fkbp1a", "a peptidyl", "peptidyl prolyl", "prolyl cis", "cis trans", "trans isomerase.", "isomerase. fkbp1a", "fkbp1a forms", "forms a", "a complex", "complex with", "with inactive", "inactive tgfbr1", "and dissociates", "dissociates from", "from it", "it only", "only after", "after tgfbr1", "recruited by", "by tgfb1", "tgfb1 bound", "bound tgfbr2", "chen et", "al. 1997", "1997 .", ".

both", "

both tgfbr1", "tgfbr2 are", "are receptor", "receptor serine/threonine", "serine/threonine kinases.", "kinases. formation", "the hetero", "hetero tetrameric", "tetrameric tgf", "in response", "response to", "to tgfb1", "tgfb1 binding", "binding induces", "induces receptor", "receptor rotation", "so that", "that tgfbr2", "tgfbr2 and", "tgfbr1 cytoplasmic", "cytoplasmic kinase", "kinase domains", "domains face", "face each", "each other", "other in", "in a", "a catalytically", "catalytically favourable", "favourable configuration.", "configuration. tgfbr2", "tgfbr2 trans", "trans phosphorylates", "phosphorylates serine", "serine residues", "residues at", "at the", "the conserved", "conserved gly", "gly ser", "ser rich", "rich juxtapositioned", "juxtapositioned domain", "gs domain", "al. 1994", "souchelnytskyi et", "al. 1996", "activating tgfbr1.
in", "tgfbr1.
in addition", "addition to", "to phosphorylation", "tgfbr1 may", "may also", "also be", "be sumoylated", "sumoylated in", "beta stimulation.", "stimulation. sumoylation", "sumoylation enhances", "enhances tgfbr1", "tgfbr1 kinase", "kinase activity", "kang et", "2008 .", ".

the", "

the activated", "activated tgfbr", "tgfbr complex", "complex is", "is internalized", "internalized by", "by clathrin", "clathrin mediated", "mediated endocytosis", "endocytosis into", "into early", "early endosomes.", "endosomes. with", "with the", "the assistance", "assistance of", "of sara", "an early", "early endosome", "endosome membrane", "membrane protein", "phosphorylated tgfbr1", "tgfbr1 within", "within tgfbr", "complex recruits", "recruits smad2", "smad2 and/or", "and/or smad3", "i.e. r", "r smads", "tsukazaki et", "al. 1998", "1998 .", "tgfbr1 phosphorylates", "phosphorylates recruited", "recruited smad2/3", "smad2/3 on", "on two", "two c", "c terminal", "terminal serine", "al. 2001", "2001 .", ". the", "the phosphorylation", "phosphorylation changes", "changes the", "the conformation", "conformation of", "of smad2/3", "smad2/3 mh2", "mh2 domain", "promoting dissociation", "dissociation of", "smad2/3 from", "from sara", "sara and", "macias silva", "silva et", "nakao et", "and formation", "smad2/3 trimers", "chacko et", "the phosphorylated", "phosphorylated c", "terminal tail", "tail of", "smad2/3 has", "has high", "high affinity", "affinity for", "for smad4", "co smad", "inducing formation", "of smad2/3:smad4", "smad2/3:smad4 heterotrimers", "composed of", "of two", "two phosphorylated", "phosphorylated r", "and smad4", "smad .", ". smad2/3:smad4", "heterotrimers are", "are energetically", "energetically favored", "favored over", "over r", "r smad", "smad trimers", "qin et", "kawabata et", ".
smad2/3:smad4", "
smad2/3:smad4 heterotrimers", "heterotrimers translocate", "translocate to", "the nucleus", "nucleus where", "where they", "they act", "act as", "as transcriptional", "transcriptional regulators.", "binding of transforming", "of transforming growth", "transforming growth factor", "growth factor beta", "factor beta 1", "1 tgf", "tgf beta 1", "1 i.e.", "tgfb1 to", "to tgf beta", "beta receptor type", "receptor type 2", "2 tgfbr2", "tgfbr2 activates", "activates tgf beta", "receptor signaling cascade.", "signaling cascade. tgfb1", "cascade. tgfb1 is", "tgfb1 is posttranslationally", "is posttranslationally processed", "posttranslationally processed by", "processed by furin", "furin dubois", "dubois et al.", "et al. 1995", "1995 to", "to form a", "form a homodimer", "a homodimer and", "homodimer and secreted", "and secreted to", "secreted to the", "to the extracellular", "the extracellular space", "extracellular space as", "space as part", "as part of", "part of the", "of the large", "the large latent", "large latent complex", "complex llc", "llc . after", ". after the", "after the llc", "the llc disassembles", "llc disassembles in", "disassembles in the", "in the extracellular", "space dimeric", "dimeric tgfb1 becomes", "tgfb1 becomes capable", "becomes capable of", "capable of binding", "of binding to", "binding to tgfbr2", "tgfbr2 annes", "annes et al.", "et al. 2003", "2003 keski", "keski oja et", "oja et al.", "et al. 2004", "al. 2004 .", "2004 . formation", ". formation of", "formation of tgfb1:tgfbr2", "of tgfb1:tgfbr2 complex", "tgfb1:tgfbr2 complex creates", "complex creates a", "creates a binding", "a binding pocket", "binding pocket for", "pocket for tgf", "for tgf beta", "receptor type 1", "1 tgfbr1", "and tgfbr1 is", "tgfbr1 is recruited", "is recruited to", "recruited to the", "to the complex", "the complex by", "complex by binding", "by binding to", "binding to both", "to both tgfb1", "both tgfb1 and", "tgfb1 and tgfbr2.", "and tgfbr2. this", "tgfbr2. this results", "this results in", "results in an", "in an active", "an active heterotetrameric", "active heterotetrameric tgf", "heterotetrameric tgf beta", "beta receptor complex", "receptor complex that", "complex that consists", "that consists of", "consists of tgfb1", "of tgfb1 homodimer", "tgfb1 homodimer bound", "homodimer bound to", "bound to two", "to two heterodimers", "two heterodimers of", "heterodimers of tgfbr1", "of tgfbr1 and", "tgfbr1 and tgfbr2", "tgfbr2 wrana", "wrana et al.", "et al. 1992", "1992 moustakas", "moustakas et al.", "et al. 1993", "1993 franzen", "franzen et al.", "al. 1993 .", "1993 . tgf", ". tgf beta", "tgf beta signaling", "beta signaling can", "signaling can also", "can also occur", "also occur through", "occur through a", "through a single", "a single heterodimer", "single heterodimer of", "heterodimer of tgfbr1", "tgfbr2 although", "although with decreased", "with decreased efficiency", "efficiency huang", "huang et al.", "et al. 2011", "al. 2011 .", "2011 . tgfbr1", ". tgfbr1 and", "and tgfbr2 interact", "tgfbr2 interact through", "interact through their", "through their extracellular", "their extracellular domains", "domains which", "which brings their", "brings their cytoplasmic", "their cytoplasmic domains", "cytoplasmic domains together.", "domains together. ligand", "together. ligand binding", "ligand binding to", "binding to extracellular", "to extracellular receptor", "extracellular receptor domains", "receptor domains is", "domains is cooperative", "cooperative but", "but no conformational", "no conformational change", "conformational change is", "change is seen", "is seen from", "seen from crystal", "from crystal structures", "crystal structures of", "structures of either", "of either tgfb1", "tgfb1 or", "or tgfb3 bound", "tgfb3 bound heterotetrameric", "bound heterotetrameric receptor", "heterotetrameric receptor complexes", "complexes groppe", "groppe et al.", "et al. 2008", "2008 radaev", "radaev et al.", "et al. 2010", "al. 2010 .

activation", "2010 .

activation of", ".

activation of tgfbr1", "of tgfbr1 by", "tgfbr1 by tgfbr2", "by tgfbr2 in", "tgfbr2 in the", "in the absence", "the absence of", "absence of ligand", "of ligand is", "ligand is prevented", "is prevented by", "prevented by fkbp1a", "fkbp1a fkbp12", "a peptidyl prolyl", "peptidyl prolyl cis", "prolyl cis trans", "cis trans isomerase.", "trans isomerase. fkbp1a", "isomerase. fkbp1a forms", "fkbp1a forms a", "forms a complex", "a complex with", "complex with inactive", "with inactive tgfbr1", "inactive tgfbr1 and", "tgfbr1 and dissociates", "and dissociates from", "dissociates from it", "from it only", "it only after", "only after tgfbr1", "after tgfbr1 is", "is recruited by", "recruited by tgfb1", "by tgfb1 bound", "tgfb1 bound tgfbr2", "tgfbr2 chen", "chen et al.", "et al. 1997", "al. 1997 .", "1997 .

both", ".

both tgfbr1", "

both tgfbr1 and", "and tgfbr2 are", "tgfbr2 are receptor", "are receptor serine/threonine", "receptor serine/threonine kinases.", "serine/threonine kinases. formation", "kinases. formation of", "formation of the", "of the hetero", "the hetero tetrameric", "hetero tetrameric tgf", "tetrameric tgf beta", "complex tgfbr", "tgfbr in", "in response to", "response to tgfb1", "to tgfb1 binding", "tgfb1 binding induces", "binding induces receptor", "induces receptor rotation", "rotation so", "so that tgfbr2", "that tgfbr2 and", "tgfbr2 and tgfbr1", "and tgfbr1 cytoplasmic", "tgfbr1 cytoplasmic kinase", "cytoplasmic kinase domains", "kinase domains face", "domains face each", "face each other", "each other in", "other in a", "in a catalytically", "a catalytically favourable", "catalytically favourable configuration.", "favourable configuration. tgfbr2", "configuration. tgfbr2 trans", "tgfbr2 trans phosphorylates", "trans phosphorylates serine", "phosphorylates serine residues", "serine residues at", "residues at the", "at the conserved", "the conserved gly", "conserved gly ser", "gly ser rich", "ser rich juxtapositioned", "rich juxtapositioned domain", "domain gs", "domain of", "tgfbr1 wrana", "et al. 1994", "1994 souchelnytskyi", "souchelnytskyi et al.", "et al. 1996", "activating tgfbr1.
in addition", "tgfbr1.
in addition to", "addition to phosphorylation", "phosphorylation tgfbr1", "tgfbr1 may also", "may also be", "also be sumoylated", "be sumoylated in", "sumoylated in response", "response to tgf", "tgf beta stimulation.", "beta stimulation. sumoylation", "stimulation. sumoylation enhances", "sumoylation enhances tgfbr1", "enhances tgfbr1 kinase", "tgfbr1 kinase activity", "activity kang", "kang et al.", "al. 2008 .", "2008 .

the", ".

the activated", "

the activated tgfbr", "activated tgfbr complex", "tgfbr complex is", "complex is internalized", "is internalized by", "internalized by clathrin", "by clathrin mediated", "clathrin mediated endocytosis", "mediated endocytosis into", "endocytosis into early", "into early endosomes.", "early endosomes. with", "endosomes. with the", "with the assistance", "the assistance of", "assistance of sara", "sara an", "an early endosome", "early endosome membrane", "endosome membrane protein", "protein phosphorylated", "phosphorylated tgfbr1 within", "tgfbr1 within tgfbr", "within tgfbr complex", "tgfbr complex recruits", "complex recruits smad2", "recruits smad2 and/or", "smad2 and/or smad3", "i.e. r smads", "smads tsukazaki", "tsukazaki et al.", "et al. 1998", "al. 1998 .", "1998 . tgfbr1", ". tgfbr1 phosphorylates", "tgfbr1 phosphorylates recruited", "phosphorylates recruited smad2/3", "recruited smad2/3 on", "smad2/3 on two", "on two c", "two c terminal", "c terminal serine", "terminal serine residues", "residues souchelnytskyi", "et al. 2001", "al. 2001 .", "2001 . the", ". the phosphorylation", "the phosphorylation changes", "phosphorylation changes the", "changes the conformation", "the conformation of", "conformation of smad2/3", "of smad2/3 mh2", "smad2/3 mh2 domain", "domain promoting", "promoting dissociation of", "dissociation of smad2/3", "of smad2/3 from", "smad2/3 from sara", "from sara and", "sara and tgfbr1", "tgfbr1 souchelnytskyi", "1997 macias", "macias silva et", "silva et al.", "1996 nakao", "nakao et al.", "1997 and", "and formation of", "formation of smad2/3", "of smad2/3 trimers", "trimers chacko", "chacko et al.", "2004 . the", ". the phosphorylated", "the phosphorylated c", "phosphorylated c terminal", "c terminal tail", "terminal tail of", "tail of smad2/3", "of smad2/3 has", "smad2/3 has high", "has high affinity", "high affinity for", "affinity for smad4", "smad4 co", "inducing formation of", "formation of smad2/3:smad4", "of smad2/3:smad4 heterotrimers", "heterotrimers composed", "composed of two", "of two phosphorylated", "two phosphorylated r", "phosphorylated r smads", "smads smad2", "smad3 and", "co smad .", "smad . smad2/3:smad4", ". smad2/3:smad4 heterotrimers", "smad2/3:smad4 heterotrimers are", "heterotrimers are energetically", "are energetically favored", "energetically favored over", "favored over r", "over r smad", "r smad trimers", "trimers nakao", "1997 qin", "qin et al.", "2001 kawabata", "kawabata et al.", "1998 chacko", "2004 .
smad2/3:smad4", ".
smad2/3:smad4 heterotrimers", "
smad2/3:smad4 heterotrimers translocate", "heterotrimers translocate to", "translocate to the", "to the nucleus", "the nucleus where", "nucleus where they", "where they act", "they act as", "act as transcriptional", "as transcriptional regulators.", "binding of transforming growth", "of transforming growth factor", "transforming growth factor beta", "growth factor beta 1", "beta 1 tgf", "1 tgf beta", "beta 1 i.e.", "1 i.e. tgfb1", "i.e. tgfb1 to", "tgfb1 to tgf", "to tgf beta receptor", "tgf beta receptor type", "beta receptor type 2", "type 2 tgfbr2", "tgfbr2 activates tgf", "activates tgf beta receptor", "beta receptor signaling cascade.", "receptor signaling cascade. tgfb1", "signaling cascade. tgfb1 is", "cascade. tgfb1 is posttranslationally", "tgfb1 is posttranslationally processed", "is posttranslationally processed by", "posttranslationally processed by furin", "by furin dubois", "furin dubois et", "dubois et al. 1995", "al. 1995 to", "1995 to form", "to form a homodimer", "form a homodimer and", "a homodimer and secreted", "homodimer and secreted to", "and secreted to the", "secreted to the extracellular", "to the extracellular space", "the extracellular space as", "extracellular space as part", "space as part of", "as part of the", "part of the large", "of the large latent", "the large latent complex", "latent complex llc", "complex llc .", "llc . after the", ". after the llc", "after the llc disassembles", "the llc disassembles in", "llc disassembles in the", "disassembles in the extracellular", "in the extracellular space", "extracellular space dimeric", "space dimeric tgfb1", "dimeric tgfb1 becomes capable", "tgfb1 becomes capable of", "becomes capable of binding", "capable of binding to", "of binding to tgfbr2", "to tgfbr2 annes", "tgfbr2 annes et", "annes et al. 2003", "al. 2003 keski", "2003 keski oja", "keski oja et al.", "oja et al. 2004", "et al. 2004 .", "al. 2004 . formation", "2004 . formation of", ". formation of tgfb1:tgfbr2", "formation of tgfb1:tgfbr2 complex", "of tgfb1:tgfbr2 complex creates", "tgfb1:tgfbr2 complex creates a", "complex creates a binding", "creates a binding pocket", "a binding pocket for", "binding pocket for tgf", "pocket for tgf beta", "for tgf beta receptor", "beta receptor type 1", "type 1 tgfbr1", "tgfbr1 and tgfbr1", "and tgfbr1 is recruited", "tgfbr1 is recruited to", "is recruited to the", "recruited to the complex", "to the complex by", "the complex by binding", "complex by binding to", "by binding to both", "binding to both tgfb1", "to both tgfb1 and", "both tgfb1 and tgfbr2.", "tgfb1 and tgfbr2. this", "and tgfbr2. this results", "tgfbr2. this results in", "this results in an", "results in an active", "in an active heterotetrameric", "an active heterotetrameric tgf", "active heterotetrameric tgf beta", "heterotetrameric tgf beta receptor", "tgf beta receptor complex", "beta receptor complex that", "receptor complex that consists", "complex that consists of", "that consists of tgfb1", "consists of tgfb1 homodimer", "of tgfb1 homodimer bound", "tgfb1 homodimer bound to", "homodimer bound to two", "bound to two heterodimers", "to two heterodimers of", "two heterodimers of tgfbr1", "heterodimers of tgfbr1 and", "of tgfbr1 and tgfbr2", "and tgfbr2 wrana", "tgfbr2 wrana et", "wrana et al. 1992", "al. 1992 moustakas", "1992 moustakas et", "moustakas et al. 1993", "al. 1993 franzen", "1993 franzen et", "franzen et al. 1993", "et al. 1993 .", "al. 1993 . tgf", "1993 . tgf beta", ". tgf beta signaling", "tgf beta signaling can", "beta signaling can also", "signaling can also occur", "can also occur through", "also occur through a", "occur through a single", "through a single heterodimer", "a single heterodimer of", "single heterodimer of tgfbr1", "heterodimer of tgfbr1 and", "and tgfbr2 although", "tgfbr2 although with", "although with decreased efficiency", "decreased efficiency huang", "efficiency huang et", "huang et al. 2011", "et al. 2011 .", "al. 2011 . tgfbr1", "2011 . tgfbr1 and", ". tgfbr1 and tgfbr2", "tgfbr1 and tgfbr2 interact", "and tgfbr2 interact through", "tgfbr2 interact through their", "interact through their extracellular", "through their extracellular domains", "extracellular domains which", "domains which brings", "which brings their cytoplasmic", "brings their cytoplasmic domains", "their cytoplasmic domains together.", "cytoplasmic domains together. ligand", "domains together. ligand binding", "together. ligand binding to", "ligand binding to extracellular", "binding to extracellular receptor", "to extracellular receptor domains", "extracellular receptor domains is", "receptor domains is cooperative", "is cooperative but", "cooperative but no", "but no conformational change", "no conformational change is", "conformational change is seen", "change is seen from", "is seen from crystal", "seen from crystal structures", "from crystal structures of", "crystal structures of either", "structures of either tgfb1", "either tgfb1 or", "tgfb1 or tgfb3", "or tgfb3 bound heterotetrameric", "tgfb3 bound heterotetrameric receptor", "bound heterotetrameric receptor complexes", "receptor complexes groppe", "complexes groppe et", "groppe et al. 2008", "al. 2008 radaev", "2008 radaev et", "radaev et al. 2010", "et al. 2010 .

activation", "al. 2010 .

activation of", "2010 .

activation of tgfbr1", ".

activation of tgfbr1 by", "of tgfbr1 by tgfbr2", "tgfbr1 by tgfbr2 in", "by tgfbr2 in the", "tgfbr2 in the absence", "in the absence of", "the absence of ligand", "absence of ligand is", "of ligand is prevented", "ligand is prevented by", "is prevented by fkbp1a", "by fkbp1a fkbp12", "fkbp12 a", "a peptidyl prolyl cis", "peptidyl prolyl cis trans", "prolyl cis trans isomerase.", "cis trans isomerase. fkbp1a", "trans isomerase. fkbp1a forms", "isomerase. fkbp1a forms a", "fkbp1a forms a complex", "forms a complex with", "a complex with inactive", "complex with inactive tgfbr1", "with inactive tgfbr1 and", "inactive tgfbr1 and dissociates", "tgfbr1 and dissociates from", "and dissociates from it", "dissociates from it only", "from it only after", "it only after tgfbr1", "only after tgfbr1 is", "after tgfbr1 is recruited", "tgfbr1 is recruited by", "is recruited by tgfb1", "recruited by tgfb1 bound", "by tgfb1 bound tgfbr2", "bound tgfbr2 chen", "tgfbr2 chen et", "chen et al. 1997", "et al. 1997 .", "al. 1997 .

both", "1997 .

both tgfbr1", ".

both tgfbr1 and", "

both tgfbr1 and tgfbr2", "tgfbr1 and tgfbr2 are", "and tgfbr2 are receptor", "tgfbr2 are receptor serine/threonine", "are receptor serine/threonine kinases.", "receptor serine/threonine kinases. formation", "serine/threonine kinases. formation of", "kinases. formation of the", "formation of the hetero", "of the hetero tetrameric", "the hetero tetrameric tgf", "hetero tetrameric tgf beta", "tetrameric tgf beta receptor", "receptor complex tgfbr", "tgfbr in response", "in response to tgfb1", "response to tgfb1 binding", "to tgfb1 binding induces", "tgfb1 binding induces receptor", "binding induces receptor rotation", "receptor rotation so", "rotation so that", "so that tgfbr2 and", "that tgfbr2 and tgfbr1", "tgfbr2 and tgfbr1 cytoplasmic", "and tgfbr1 cytoplasmic kinase", "tgfbr1 cytoplasmic kinase domains", "cytoplasmic kinase domains face", "kinase domains face each", "domains face each other", "face each other in", "each other in a", "other in a catalytically", "in a catalytically favourable", "a catalytically favourable configuration.", "catalytically favourable configuration. tgfbr2", "favourable configuration. tgfbr2 trans", "configuration. tgfbr2 trans phosphorylates", "tgfbr2 trans phosphorylates serine", "trans phosphorylates serine residues", "phosphorylates serine residues at", "serine residues at the", "residues at the conserved", "at the conserved gly", "the conserved gly ser", "conserved gly ser rich", "gly ser rich juxtapositioned", "ser rich juxtapositioned domain", "juxtapositioned domain gs", "domain gs domain", "gs domain of", "domain of tgfbr1", "of tgfbr1 wrana", "tgfbr1 wrana et", "wrana et al. 1994", "al. 1994 souchelnytskyi", "1994 souchelnytskyi et", "souchelnytskyi et al. 1996", "1996 activating", "activating tgfbr1.
in addition to", "tgfbr1.
in addition to phosphorylation", "to phosphorylation tgfbr1", "phosphorylation tgfbr1 may", "tgfbr1 may also be", "may also be sumoylated", "also be sumoylated in", "be sumoylated in response", "sumoylated in response to", "in response to tgf", "response to tgf beta", "to tgf beta stimulation.", "tgf beta stimulation. sumoylation", "beta stimulation. sumoylation enhances", "stimulation. sumoylation enhances tgfbr1", "sumoylation enhances tgfbr1 kinase", "enhances tgfbr1 kinase activity", "kinase activity kang", "activity kang et", "kang et al. 2008", "et al. 2008 .", "al. 2008 .

the", "2008 .

the activated", ".

the activated tgfbr", "

the activated tgfbr complex", "activated tgfbr complex is", "tgfbr complex is internalized", "complex is internalized by", "is internalized by clathrin", "internalized by clathrin mediated", "by clathrin mediated endocytosis", "clathrin mediated endocytosis into", "mediated endocytosis into early", "endocytosis into early endosomes.", "into early endosomes. with", "early endosomes. with the", "endosomes. with the assistance", "with the assistance of", "the assistance of sara", "of sara an", "sara an early", "an early endosome membrane", "early endosome membrane protein", "membrane protein phosphorylated", "protein phosphorylated tgfbr1", "phosphorylated tgfbr1 within tgfbr", "tgfbr1 within tgfbr complex", "within tgfbr complex recruits", "tgfbr complex recruits smad2", "complex recruits smad2 and/or", "recruits smad2 and/or smad3", "smad3 i.e.", "r smads tsukazaki", "smads tsukazaki et", "tsukazaki et al. 1998", "et al. 1998 .", "al. 1998 . tgfbr1", "1998 . tgfbr1 phosphorylates", ". tgfbr1 phosphorylates recruited", "tgfbr1 phosphorylates recruited smad2/3", "phosphorylates recruited smad2/3 on", "recruited smad2/3 on two", "smad2/3 on two c", "on two c terminal", "two c terminal serine", "c terminal serine residues", "serine residues souchelnytskyi", "residues souchelnytskyi et", "souchelnytskyi et al. 2001", "et al. 2001 .", "al. 2001 . the", "2001 . the phosphorylation", ". the phosphorylation changes", "the phosphorylation changes the", "phosphorylation changes the conformation", "changes the conformation of", "the conformation of smad2/3", "conformation of smad2/3 mh2", "of smad2/3 mh2 domain", "mh2 domain promoting", "domain promoting dissociation", "promoting dissociation of smad2/3", "dissociation of smad2/3 from", "of smad2/3 from sara", "smad2/3 from sara and", "from sara and tgfbr1", "and tgfbr1 souchelnytskyi", "tgfbr1 souchelnytskyi et", "souchelnytskyi et al. 1997", "al. 1997 macias", "1997 macias silva", "macias silva et al.", "silva et al. 1996", "al. 1996 nakao", "1996 nakao et", "nakao et al. 1997", "al. 1997 and", "1997 and formation", "and formation of smad2/3", "formation of smad2/3 trimers", "smad2/3 trimers chacko", "trimers chacko et", "chacko et al. 2004", "al. 2004 . the", "2004 . the phosphorylated", ". the phosphorylated c", "the phosphorylated c terminal", "phosphorylated c terminal tail", "c terminal tail of", "terminal tail of smad2/3", "tail of smad2/3 has", "of smad2/3 has high", "smad2/3 has high affinity", "has high affinity for", "high affinity for smad4", "for smad4 co", "smad4 co smad", "smad inducing", "inducing formation of smad2/3:smad4", "formation of smad2/3:smad4 heterotrimers", "smad2/3:smad4 heterotrimers composed", "heterotrimers composed of", "composed of two phosphorylated", "of two phosphorylated r", "two phosphorylated r smads", "r smads smad2", "smads smad2 and/or", "and/or smad3 and", "smad3 and smad4", "and smad4 co", "co smad . smad2/3:smad4", "smad . smad2/3:smad4 heterotrimers", ". smad2/3:smad4 heterotrimers are", "smad2/3:smad4 heterotrimers are energetically", "heterotrimers are energetically favored", "are energetically favored over", "energetically favored over r", "favored over r smad", "over r smad trimers", "smad trimers nakao", "trimers nakao et", "al. 1997 qin", "1997 qin et", "qin et al. 2001", "al. 2001 kawabata", "2001 kawabata et", "kawabata et al. 1998", "al. 1998 chacko", "1998 chacko et", "al. 2004 .
smad2/3:smad4", "2004 .
smad2/3:smad4 heterotrimers", ".
smad2/3:smad4 heterotrimers translocate", "
smad2/3:smad4 heterotrimers translocate to", "heterotrimers translocate to the", "translocate to the nucleus", "to the nucleus where", "the nucleus where they", "nucleus where they act", "where they act as", "they act as transcriptional", "act as transcriptional regulators.", "binding of transforming growth factor", "of transforming growth factor beta", "transforming growth factor beta 1", "factor beta 1 tgf", "beta 1 tgf beta", "1 tgf beta 1", "tgf beta 1 i.e.", "beta 1 i.e. tgfb1", "i.e. tgfb1 to tgf", "tgfb1 to tgf beta", "to tgf beta receptor type", "tgf beta receptor type 2", "receptor type 2 tgfbr2", "2 tgfbr2 activates", "tgfbr2 activates tgf beta", "activates tgf beta receptor signaling", "tgf beta receptor signaling cascade.", "beta receptor signaling cascade. tgfb1", "receptor signaling cascade. tgfb1 is", "signaling cascade. tgfb1 is posttranslationally", "cascade. tgfb1 is posttranslationally processed", "tgfb1 is posttranslationally processed by", "is posttranslationally processed by furin", "processed by furin dubois", "by furin dubois et", "furin dubois et al.", "et al. 1995 to", "al. 1995 to form", "1995 to form a", "to form a homodimer and", "form a homodimer and secreted", "a homodimer and secreted to", "homodimer and secreted to the", "and secreted to the extracellular", "secreted to the extracellular space", "to the extracellular space as", "the extracellular space as part", "extracellular space as part of", "space as part of the", "as part of the large", "part of the large latent", "of the large latent complex", "large latent complex llc", "latent complex llc .", "complex llc . after", "llc . after the llc", ". after the llc disassembles", "after the llc disassembles in", "the llc disassembles in the", "llc disassembles in the extracellular", "disassembles in the extracellular space", "the extracellular space dimeric", "extracellular space dimeric tgfb1", "space dimeric tgfb1 becomes", "dimeric tgfb1 becomes capable of", "tgfb1 becomes capable of binding", "becomes capable of binding to", "capable of binding to tgfbr2", "binding to tgfbr2 annes", "to tgfbr2 annes et", "tgfbr2 annes et al.", "et al. 2003 keski", "al. 2003 keski oja", "2003 keski oja et", "keski oja et al. 2004", "oja et al. 2004 .", "et al. 2004 . formation", "al. 2004 . formation of", "2004 . formation of tgfb1:tgfbr2", ". formation of tgfb1:tgfbr2 complex", "formation of tgfb1:tgfbr2 complex creates", "of tgfb1:tgfbr2 complex creates a", "tgfb1:tgfbr2 complex creates a binding", "complex creates a binding pocket", "creates a binding pocket for", "a binding pocket for tgf", "binding pocket for tgf beta", "pocket for tgf beta receptor", "for tgf beta receptor type", "tgf beta receptor type 1", "receptor type 1 tgfbr1", "1 tgfbr1 and", "tgfbr1 and tgfbr1 is", "and tgfbr1 is recruited to", "tgfbr1 is recruited to the", "is recruited to the complex", "recruited to the complex by", "to the complex by binding", "the complex by binding to", "complex by binding to both", "by binding to both tgfb1", "binding to both tgfb1 and", "to both tgfb1 and tgfbr2.", "both tgfb1 and tgfbr2. this", "tgfb1 and tgfbr2. this results", "and tgfbr2. this results in", "tgfbr2. this results in an", "this results in an active", "results in an active heterotetrameric", "in an active heterotetrameric tgf", "an active heterotetrameric tgf beta", "active heterotetrameric tgf beta receptor", "heterotetrameric tgf beta receptor complex", "tgf beta receptor complex that", "beta receptor complex that consists", "receptor complex that consists of", "complex that consists of tgfb1", "that consists of tgfb1 homodimer", "consists of tgfb1 homodimer bound", "of tgfb1 homodimer bound to", "tgfb1 homodimer bound to two", "homodimer bound to two heterodimers", "bound to two heterodimers of", "to two heterodimers of tgfbr1", "two heterodimers of tgfbr1 and", "heterodimers of tgfbr1 and tgfbr2", "tgfbr1 and tgfbr2 wrana", "and tgfbr2 wrana et", "tgfbr2 wrana et al.", "et al. 1992 moustakas", "al. 1992 moustakas et", "1992 moustakas et al.", "et al. 1993 franzen", "al. 1993 franzen et", "1993 franzen et al.", "franzen et al. 1993 .", "et al. 1993 . tgf", "al. 1993 . tgf beta", "1993 . tgf beta signaling", ". tgf beta signaling can", "tgf beta signaling can also", "beta signaling can also occur", "signaling can also occur through", "can also occur through a", "also occur through a single", "occur through a single heterodimer", "through a single heterodimer of", "a single heterodimer of tgfbr1", "single heterodimer of tgfbr1 and", "heterodimer of tgfbr1 and tgfbr2", "tgfbr1 and tgfbr2 although", "and tgfbr2 although with", "tgfbr2 although with decreased", "with decreased efficiency huang", "decreased efficiency huang et", "efficiency huang et al.", "huang et al. 2011 .", "et al. 2011 . tgfbr1", "al. 2011 . tgfbr1 and", "2011 . tgfbr1 and tgfbr2", ". tgfbr1 and tgfbr2 interact", "tgfbr1 and tgfbr2 interact through", "and tgfbr2 interact through their", "tgfbr2 interact through their extracellular", "interact through their extracellular domains", "their extracellular domains which", "extracellular domains which brings", "domains which brings their", "which brings their cytoplasmic domains", "brings their cytoplasmic domains together.", "their cytoplasmic domains together. ligand", "cytoplasmic domains together. ligand binding", "domains together. ligand binding to", "together. ligand binding to extracellular", "ligand binding to extracellular receptor", "binding to extracellular receptor domains", "to extracellular receptor domains is", "extracellular receptor domains is cooperative", "domains is cooperative but", "is cooperative but no", "cooperative but no conformational", "but no conformational change is", "no conformational change is seen", "conformational change is seen from", "change is seen from crystal", "is seen from crystal structures", "seen from crystal structures of", "from crystal structures of either", "crystal structures of either tgfb1", "of either tgfb1 or", "either tgfb1 or tgfb3", "tgfb1 or tgfb3 bound", "or tgfb3 bound heterotetrameric receptor", "tgfb3 bound heterotetrameric receptor complexes", "heterotetrameric receptor complexes groppe", "receptor complexes groppe et", "complexes groppe et al.", "et al. 2008 radaev", "al. 2008 radaev et", "2008 radaev et al.", "radaev et al. 2010 .

activation", "et al. 2010 .

activation of", "al. 2010 .

activation of tgfbr1", "2010 .

activation of tgfbr1 by", ".

activation of tgfbr1 by tgfbr2", "of tgfbr1 by tgfbr2 in", "tgfbr1 by tgfbr2 in the", "by tgfbr2 in the absence", "tgfbr2 in the absence of", "in the absence of ligand", "the absence of ligand is", "absence of ligand is prevented", "of ligand is prevented by", "ligand is prevented by fkbp1a", "prevented by fkbp1a fkbp12", "fkbp12 a peptidyl", "a peptidyl prolyl cis trans", "peptidyl prolyl cis trans isomerase.", "prolyl cis trans isomerase. fkbp1a", "cis trans isomerase. fkbp1a forms", "trans isomerase. fkbp1a forms a", "isomerase. fkbp1a forms a complex", "fkbp1a forms a complex with", "forms a complex with inactive", "a complex with inactive tgfbr1", "complex with inactive tgfbr1 and", "with inactive tgfbr1 and dissociates", "inactive tgfbr1 and dissociates from", "tgfbr1 and dissociates from it", "and dissociates from it only", "dissociates from it only after", "from it only after tgfbr1", "it only after tgfbr1 is", "only after tgfbr1 is recruited", "after tgfbr1 is recruited by", "tgfbr1 is recruited by tgfb1", "is recruited by tgfb1 bound", "recruited by tgfb1 bound tgfbr2", "tgfb1 bound tgfbr2 chen", "bound tgfbr2 chen et", "tgfbr2 chen et al.", "chen et al. 1997 .", "et al. 1997 .

both", "al. 1997 .

both tgfbr1", "1997 .

both tgfbr1 and", ".

both tgfbr1 and tgfbr2", "

both tgfbr1 and tgfbr2 are", "tgfbr1 and tgfbr2 are receptor", "and tgfbr2 are receptor serine/threonine", "tgfbr2 are receptor serine/threonine kinases.", "are receptor serine/threonine kinases. formation", "receptor serine/threonine kinases. formation of", "serine/threonine kinases. formation of the", "kinases. formation of the hetero", "formation of the hetero tetrameric", "of the hetero tetrameric tgf", "the hetero tetrameric tgf beta", "hetero tetrameric tgf beta receptor", "tetrameric tgf beta receptor complex", "beta receptor complex tgfbr", "complex tgfbr in", "tgfbr in response to", "in response to tgfb1 binding", "response to tgfb1 binding induces", "to tgfb1 binding induces receptor", "tgfb1 binding induces receptor rotation", "induces receptor rotation so", "receptor rotation so that", "rotation so that tgfbr2", "so that tgfbr2 and tgfbr1", "that tgfbr2 and tgfbr1 cytoplasmic", "tgfbr2 and tgfbr1 cytoplasmic kinase", "and tgfbr1 cytoplasmic kinase domains", "tgfbr1 cytoplasmic kinase domains face", "cytoplasmic kinase domains face each", "kinase domains face each other", "domains face each other in", "face each other in a", "each other in a catalytically", "other in a catalytically favourable", "in a catalytically favourable configuration.", "a catalytically favourable configuration. tgfbr2", "catalytically favourable configuration. tgfbr2 trans", "favourable configuration. tgfbr2 trans phosphorylates", "configuration. tgfbr2 trans phosphorylates serine", "tgfbr2 trans phosphorylates serine residues", "trans phosphorylates serine residues at", "phosphorylates serine residues at the", "serine residues at the conserved", "residues at the conserved gly", "at the conserved gly ser", "the conserved gly ser rich", "conserved gly ser rich juxtapositioned", "gly ser rich juxtapositioned domain", "rich juxtapositioned domain gs", "juxtapositioned domain gs domain", "gs domain of tgfbr1", "of tgfbr1 wrana et", "tgfbr1 wrana et al.", "et al. 1994 souchelnytskyi", "al. 1994 souchelnytskyi et", "1994 souchelnytskyi et al.", "al. 1996 activating", "1996 activating tgfbr1.
in", "activating tgfbr1.
in addition to phosphorylation", "addition to phosphorylation tgfbr1", "to phosphorylation tgfbr1 may", "phosphorylation tgfbr1 may also", "tgfbr1 may also be sumoylated", "may also be sumoylated in", "also be sumoylated in response", "be sumoylated in response to", "sumoylated in response to tgf", "in response to tgf beta", "response to tgf beta stimulation.", "to tgf beta stimulation. sumoylation", "tgf beta stimulation. sumoylation enhances", "beta stimulation. sumoylation enhances tgfbr1", "stimulation. sumoylation enhances tgfbr1 kinase", "sumoylation enhances tgfbr1 kinase activity", "tgfbr1 kinase activity kang", "kinase activity kang et", "activity kang et al.", "kang et al. 2008 .", "et al. 2008 .

the", "al. 2008 .

the activated", "2008 .

the activated tgfbr", ".

the activated tgfbr complex", "

the activated tgfbr complex is", "activated tgfbr complex is internalized", "tgfbr complex is internalized by", "complex is internalized by clathrin", "is internalized by clathrin mediated", "internalized by clathrin mediated endocytosis", "by clathrin mediated endocytosis into", "clathrin mediated endocytosis into early", "mediated endocytosis into early endosomes.", "endocytosis into early endosomes. with", "into early endosomes. with the", "early endosomes. with the assistance", "endosomes. with the assistance of", "with the assistance of sara", "assistance of sara an", "of sara an early", "sara an early endosome", "an early endosome membrane protein", "endosome membrane protein phosphorylated", "membrane protein phosphorylated tgfbr1", "protein phosphorylated tgfbr1 within", "phosphorylated tgfbr1 within tgfbr complex", "tgfbr1 within tgfbr complex recruits", "within tgfbr complex recruits smad2", "tgfbr complex recruits smad2 and/or", "complex recruits smad2 and/or smad3", "and/or smad3 i.e.", "smad3 i.e. r", "i.e. r smads tsukazaki", "r smads tsukazaki et", "smads tsukazaki et al.", "tsukazaki et al. 1998 .", "et al. 1998 . tgfbr1", "al. 1998 . tgfbr1 phosphorylates", "1998 . tgfbr1 phosphorylates recruited", ". tgfbr1 phosphorylates recruited smad2/3", "tgfbr1 phosphorylates recruited smad2/3 on", "phosphorylates recruited smad2/3 on two", "recruited smad2/3 on two c", "smad2/3 on two c terminal", "on two c terminal serine", "two c terminal serine residues", "terminal serine residues souchelnytskyi", "serine residues souchelnytskyi et", "residues souchelnytskyi et al.", "souchelnytskyi et al. 2001 .", "et al. 2001 . the", "al. 2001 . the phosphorylation", "2001 . the phosphorylation changes", ". the phosphorylation changes the", "the phosphorylation changes the conformation", "phosphorylation changes the conformation of", "changes the conformation of smad2/3", "the conformation of smad2/3 mh2", "conformation of smad2/3 mh2 domain", "smad2/3 mh2 domain promoting", "mh2 domain promoting dissociation", "domain promoting dissociation of", "promoting dissociation of smad2/3 from", "dissociation of smad2/3 from sara", "of smad2/3 from sara and", "smad2/3 from sara and tgfbr1", "sara and tgfbr1 souchelnytskyi", "and tgfbr1 souchelnytskyi et", "tgfbr1 souchelnytskyi et al.", "et al. 1997 macias", "al. 1997 macias silva", "1997 macias silva et", "macias silva et al. 1996", "et al. 1996 nakao", "al. 1996 nakao et", "1996 nakao et al.", "et al. 1997 and", "al. 1997 and formation", "1997 and formation of", "and formation of smad2/3 trimers", "of smad2/3 trimers chacko", "smad2/3 trimers chacko et", "trimers chacko et al.", "chacko et al. 2004 .", "et al. 2004 . the", "al. 2004 . the phosphorylated", "2004 . the phosphorylated c", ". the phosphorylated c terminal", "the phosphorylated c terminal tail", "phosphorylated c terminal tail of", "c terminal tail of smad2/3", "terminal tail of smad2/3 has", "tail of smad2/3 has high", "of smad2/3 has high affinity", "smad2/3 has high affinity for", "has high affinity for smad4", "affinity for smad4 co", "for smad4 co smad", "co smad inducing", "smad inducing formation", "inducing formation of smad2/3:smad4 heterotrimers", "of smad2/3:smad4 heterotrimers composed", "smad2/3:smad4 heterotrimers composed of", "heterotrimers composed of two", "composed of two phosphorylated r", "of two phosphorylated r smads", "phosphorylated r smads smad2", "r smads smad2 and/or", "smads smad2 and/or smad3", "smad2 and/or smad3 and", "and/or smad3 and smad4", "and smad4 co smad", "smad4 co smad .", "co smad . smad2/3:smad4 heterotrimers", "smad . smad2/3:smad4 heterotrimers are", ". smad2/3:smad4 heterotrimers are energetically", "smad2/3:smad4 heterotrimers are energetically favored", "heterotrimers are energetically favored over", "are energetically favored over r", "energetically favored over r smad", "favored over r smad trimers", "r smad trimers nakao", "smad trimers nakao et", "trimers nakao et al.", "et al. 1997 qin", "al. 1997 qin et", "1997 qin et al.", "et al. 2001 kawabata", "al. 2001 kawabata et", "2001 kawabata et al.", "et al. 1998 chacko", "al. 1998 chacko et", "1998 chacko et al.", "et al. 2004 .
smad2/3:smad4", "al. 2004 .
smad2/3:smad4 heterotrimers", "2004 .
smad2/3:smad4 heterotrimers translocate", ".
smad2/3:smad4 heterotrimers translocate to", "
smad2/3:smad4 heterotrimers translocate to the", "heterotrimers translocate to the nucleus", "translocate to the nucleus where", "to the nucleus where they", "the nucleus where they act", "nucleus where they act as", "where they act as transcriptional", "they act as transcriptional regulators." ] }, { "record_id": "GLY_000594_1_887", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2173791", "r hsa", "hsa 2173791", "r hsa 2173791" ] }, { "record_id": "GLY_000594_1_887", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tgf beta", "beta receptor", "receptor signaling", "signaling in", "in emt", "epithelial to", "to mesenchymal", "mesenchymal transition", "tgf beta receptor", "beta receptor signaling", "receptor signaling in", "signaling in emt", "emt epithelial", "epithelial to mesenchymal", "to mesenchymal transition", "tgf beta receptor signaling", "beta receptor signaling in", "receptor signaling in emt", "in emt epithelial", "emt epithelial to", "epithelial to mesenchymal transition", "tgf beta receptor signaling in", "beta receptor signaling in emt", "signaling in emt epithelial", "in emt epithelial to", "emt epithelial to mesenchymal", "in normal", "normal cells", "cells and", "and in", "in the", "the early", "early stages", "stages of", "of cancer", "cancer development", "signaling by", "by tgf", "beta plays", "plays a", "a tumor", "tumor suppressive", "suppressive role", "as smad2/3:smad4", "smad2/3:smad4 mediated", "mediated transcription", "transcription inhibits", "inhibits cell", "cell division", "division by", "by downregulating", "downregulating myc", "myc oncogene", "oncogene transcription", "transcription and", "and stimulating", "stimulating transcription", "transcription of", "of cdkn2b", "cdkn2b tumor", "tumor suppressor", "suppressor gene.", "gene. in", "in advanced", "advanced cancers", "cancers however", "beta signaling", "signaling promotes", "promotes metastasis", "metastasis by", "by stimulating", "stimulating epithelial", "emt .", ".
tgfbr1", "
tgfbr1 is", "is recruited", "recruited to", "to tight", "tight junctions", "junctions by", "by binding", "binding pard6a", "a component", "component of", "of tight", "tight junctions.", "junctions. after", "after tgf", "beta stimulation", "activated tgfbr2", "tgfbr2 binds", "binds tgfbr1", "tgfbr1 at", "at tight", "and phosphorylates", "phosphorylates both", "both tgfbr1", "tgfbr1 and", "and pard6a.", "pard6a. phosphorylated", "phosphorylated pard6a", "pard6a recruits", "recruits smurf1", "smurf1 to", "junctions. smurf1", "smurf1 is", "is able", "able to", "to ubiquitinate", "ubiquitinate rhoa", "junctions needed", "needed for", "for tight", "tight junction", "junction maintenance", "leading to", "to disassembly", "disassembly of", "an important", "important step", "step in", "wang et", "et al.", "al. 2003", "ozdamar et", "al. 2005", "2005 .", "in normal cells", "normal cells and", "cells and in", "and in the", "in the early", "the early stages", "early stages of", "stages of cancer", "of cancer development", "development signaling", "signaling by tgf", "by tgf beta", "tgf beta plays", "beta plays a", "plays a tumor", "a tumor suppressive", "tumor suppressive role", "role as", "as smad2/3:smad4 mediated", "smad2/3:smad4 mediated transcription", "mediated transcription inhibits", "transcription inhibits cell", "inhibits cell division", "cell division by", "division by downregulating", "by downregulating myc", "downregulating myc oncogene", "myc oncogene transcription", "oncogene transcription and", "transcription and stimulating", "and stimulating transcription", "stimulating transcription of", "transcription of cdkn2b", "of cdkn2b tumor", "cdkn2b tumor suppressor", "tumor suppressor gene.", "suppressor gene. in", "gene. in advanced", "in advanced cancers", "advanced cancers however", "however tgf", "tgf beta signaling", "beta signaling promotes", "signaling promotes metastasis", "promotes metastasis by", "metastasis by stimulating", "by stimulating epithelial", "stimulating epithelial to", "transition emt", "emt .
tgfbr1", ".
tgfbr1 is", "
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tgfbr1 is", ".
tgfbr1 is recruited", "
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tgfbr1", "emt .
tgfbr1 is recruited", ".
tgfbr1 is recruited to", "
tgfbr1 is recruited to tight", "is recruited to tight junctions", "recruited to tight junctions by", "to tight junctions by binding", "tight junctions by binding pard6a", "by binding pard6a a", "binding pard6a a component", "pard6a a component of", "a component of tight junctions.", "component of tight junctions. after", "of tight junctions. after tgf", "tight junctions. after tgf beta", "junctions. after tgf beta stimulation", "tgf beta stimulation activated", "beta stimulation activated tgfbr2", "stimulation activated tgfbr2 binds", "activated tgfbr2 binds tgfbr1 at", "tgfbr2 binds tgfbr1 at tight", "binds tgfbr1 at tight junctions", "at tight junctions and", "tight junctions and phosphorylates", "junctions and phosphorylates both", "and phosphorylates both tgfbr1 and", "phosphorylates both tgfbr1 and pard6a.", "both tgfbr1 and pard6a. phosphorylated", "tgfbr1 and pard6a. phosphorylated pard6a", "and pard6a. phosphorylated pard6a recruits", "pard6a. phosphorylated pard6a recruits smurf1", "phosphorylated pard6a recruits smurf1 to", "pard6a recruits smurf1 to tight", "recruits smurf1 to tight junctions.", "smurf1 to tight junctions. smurf1", "to tight junctions. smurf1 is", "tight junctions. smurf1 is able", "junctions. smurf1 is able to", "smurf1 is able to ubiquitinate", "is able to ubiquitinate rhoa", "to ubiquitinate rhoa a", "ubiquitinate rhoa a component", "rhoa a component of", "a component of tight junctions", "component of tight junctions needed", "of tight junctions needed for", "tight junctions needed for tight", "junctions needed for tight junction", "needed for tight junction maintenance", "tight junction maintenance leading", "junction maintenance leading to", "maintenance leading to disassembly", "leading to disassembly of tight", "to disassembly of tight junctions", "of tight junctions an", "tight junctions an important", "junctions an important step", "an important step in emt", "step in emt wang", "in emt wang et", "emt wang et al.", "et al. 2003 ozdamar", "al. 2003 ozdamar et", "2003 ozdamar et al.", "ozdamar et al. 2005 ." ] }, { "record_id": "GLY_000594_1_888", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2173795", "r hsa", "hsa 2173795", "r hsa 2173795" ] }, { "record_id": "GLY_000594_1_888", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "downregulation of", "of smad2/3:smad4", "smad2/3:smad4 transcriptional", "transcriptional activity", "downregulation of smad2/3:smad4", "of smad2/3:smad4 transcriptional", "smad2/3:smad4 transcriptional activity", "downregulation of smad2/3:smad4 transcriptional", "of smad2/3:smad4 transcriptional activity", "downregulation of smad2/3:smad4 transcriptional activity", "activity of", "smad2/3:smad4 heterotrimer", "heterotrimer can", "can be", "be inhibited", "inhibited by", "by formation", "formation of", "of a", "a complex", "complex with", "with ski", "ski or", "or skil", "where ski", "skil recruit", "recruit ncor", "ncor and", "and possibly", "possibly other", "other transcriptional", "transcriptional repressors", "repressors to", "to smad", "smad binding", "binding promoter", "promoter elements", "sun et", "et al.", "al. 1999", "luo et", "strochein et", "1999 .", ". higher", "higher levels", "levels of", "of phosphorylated", "phosphorylated smad2", "smad2 and", "and smad3", "may target", "target ski", "ski and", "and skil", "skil for", "for degradation", "1999 pnas", "bonni et", "al. 2001", "through recruitment", "recruitment of", "of smurf2", "or rnf111", "rnf111 i.e.", "i.e. arkadia", "levy et", "al. 2007", "ubiquitin ligases", "ligases to", "to ski/skil", "ski/skil by", "by smad2/3.", "smad2/3. therefore", "therefore the", "the ratio", "ratio of", "of smad2/3", "smad2/3 and", "and ski/skil", "ski/skil determines", "determines the", "the outcome:", "outcome: inhibition", "inhibition of", "smad2/3:smad4 mediated", "mediated transcription", "transcription or", "or degradation", "degradation of", "of ski/skil.", "ski/skil. ski", "skil are", "are overexpressed", "overexpressed in", "in various", "various cancer", "cancer types", "types and", "and their", "their oncogenic", "oncogenic effect", "effect is", "is connected", "connected with", "with their", "their ability", "ability to", "to inhibit", "inhibit signaling", "signaling by", "by tgf", "tgf beta", "beta receptor", "receptor complex.", "complex.
smad4", "
smad4 can", "be monoubiquitinated", "monoubiquitinated by", "by a", "a nuclear", "nuclear ubiquitin", "ubiquitin ligase", "ligase trim33", "tif1 gamma", "gamma .", ". monoubiquitination", "monoubiquitination of", "of smad4", "smad4 disrupts", "disrupts smad2/3:smad4", "smad2/3:smad4 heterotrimers", "heterotrimers and", "and leads", "leads to", "to smad4", "smad4 translocation", "translocation to", "to the", "the cytosol.", "cytosol. in", "in the", "the cytosol", "smad4 can", "be deubiquitinated", "deubiquitinated by", "by usp9x", "reversing trim33", "trim33 mediated", "mediated negative", "negative regulation", "dupont et", "al. 2009", "2009 .
phosphorylation", ".
phosphorylation of", "of the", "the linker", "linker region", "region of", "of smad2", "smad3 by", "by cdk8", "cdk8 or", "or cdk9", "cdk9 primes", "primes smad2/3:smad4", "smad2/3:smad4 complex", "complex for", "for ubiquitination", "ubiquitination by", "by nedd4l", "nedd4l and", "and smurf", "smurf ubiquitin", "ubiquitin ligases.", "ligases. nedd4l", "nedd4l ubiquitinates", "ubiquitinates smad2/3", "and targets", "targets smad2/3:smad4", "heterotrimer for", "gao et", "2009 .", ". smurf2", "smurf2 monoubiquitinates", "monoubiquitinates smad2/3", "leading to", "to disruption", "disruption of", "smad2/3:smad4 complexes", "tang et", "al. 2011", "2011 .", ".
transcriptional", "
transcriptional repressors", "repressors tgif1", "tgif1 and", "and tgif2", "tgif2 bind", "bind smad2/3:smad4", "complexes and", "and inhibit", "inhibit smad", "smad mediated", "transcription by", "by recruitment", "of histone", "histone deacetylase", "deacetylase hdac1", "hdac1 to", "wotton et", "melhuish et", "2001 .
parp1", ".
parp1 can", "can attach", "attach poly", "poly adp", "adp ribosyl", "ribosyl chains", "chains to", "to smad3", "smad3 and", "and smad4", "smad4 within", "within smad2/3:smad4", "smad2/3:smad4 heterotrimers.", "heterotrimers. parylated", "parylated smad2/3:smad4", "complexes are", "are unable", "unable to", "to bind", "bind smad", "binding dna", "dna elements", "lonn et", "al. 2010", "2010 .", ".
phosphorylated", "
phosphorylated smad2", "smad3 can", "be dephosphorylated", "dephosphorylated by", "by ppm1a", "ppm1a protein", "protein phosphatase", "to dissociation", "dissociation of", "smad2/3 complexes", "and translocation", "translocation of", "of unphosphorylated", "unphosphorylated smad2/3", "smad2/3 to", "lin et", "al. 2006", "2006 .", "transcriptional activity of", "activity of smad2/3:smad4", "of smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer can", "heterotrimer can be", "can be inhibited", "be inhibited by", "inhibited by formation", "by formation of", "formation of a", "of a complex", "a complex with", "complex with ski", "with ski or", "ski or skil", "skil sno", "where ski or", "or skil recruit", "skil recruit ncor", "recruit ncor and", "ncor and possibly", "and possibly other", "possibly other transcriptional", "other transcriptional repressors", "transcriptional repressors to", "repressors to smad", "to smad binding", "smad binding promoter", "binding promoter elements", "elements sun", "sun et al.", "et al. 1999", "1999 luo", "luo et al.", "1999 strochein", "strochein et al.", "al. 1999 .", "1999 . higher", ". higher levels", "higher levels of", "levels of phosphorylated", "of phosphorylated smad2", "phosphorylated smad2 and", "smad2 and smad3", "smad3 however", "however may", "may target ski", "target ski and", "ski and skil", "and skil for", "skil for degradation", "degradation strochein", "1999 sun", "al. 1999 pnas", "pnas bonni", "bonni et al.", "et al. 2001", "2001 through", "through recruitment of", "recruitment of smurf2", "smurf2 bonni", "2001 or", "or rnf111 i.e.", "rnf111 i.e. arkadia", "arkadia levy", "levy et al.", "et al. 2007", "2007 ubiquitin", "ubiquitin ligases to", "ligases to ski/skil", "to ski/skil by", "ski/skil by smad2/3.", "by smad2/3. therefore", "smad2/3. therefore the", "therefore the ratio", "the ratio of", "ratio of smad2/3", "of smad2/3 and", "smad2/3 and ski/skil", "and ski/skil determines", "ski/skil determines the", "determines the outcome:", "the outcome: inhibition", "outcome: inhibition of", "inhibition of smad2/3:smad4", "of smad2/3:smad4 mediated", "smad2/3:smad4 mediated transcription", "mediated transcription or", "transcription or degradation", "or degradation of", "degradation of ski/skil.", "of ski/skil. ski", "ski/skil. ski and", "and skil are", "skil are overexpressed", "are overexpressed in", "overexpressed in various", "in various cancer", "various cancer types", "cancer types and", "types and their", "and their oncogenic", "their oncogenic effect", "oncogenic effect is", "effect is connected", "is connected with", "connected with their", "with their ability", "their ability to", "ability to inhibit", "to inhibit signaling", "inhibit signaling by", "signaling by tgf", "by tgf beta", "tgf beta receptor", "beta receptor complex.", "receptor complex.
smad4", "complex.
smad4 can", "
smad4 can be", "can be monoubiquitinated", "be monoubiquitinated by", "monoubiquitinated by a", "by a nuclear", "a nuclear ubiquitin", "nuclear ubiquitin ligase", "ubiquitin ligase trim33", "trim33 ecto", "ecto ectodermin", "ectodermin tif1", "tif1 gamma .", "gamma . monoubiquitination", ". monoubiquitination of", "monoubiquitination of smad4", "of smad4 disrupts", "smad4 disrupts smad2/3:smad4", "disrupts smad2/3:smad4 heterotrimers", "smad2/3:smad4 heterotrimers and", "heterotrimers and leads", "and leads to", "leads to smad4", "to smad4 translocation", "smad4 translocation to", "translocation to the", "to the cytosol.", "the cytosol. in", "cytosol. in the", "in the cytosol", "cytosol smad4", "smad4 can be", "can be deubiquitinated", "be deubiquitinated by", "deubiquitinated by usp9x", "usp9x fam", "reversing trim33 mediated", "trim33 mediated negative", "mediated negative regulation", "regulation dupont", "dupont et al.", "et al. 2009", "al. 2009 .
phosphorylation", "2009 .
phosphorylation of", ".
phosphorylation of the", "of the linker", "the linker region", "linker region of", "region of smad2", "of smad2 and", "and smad3 by", "smad3 by cdk8", "by cdk8 or", "cdk8 or cdk9", "or cdk9 primes", "cdk9 primes smad2/3:smad4", "primes smad2/3:smad4 complex", "smad2/3:smad4 complex for", "complex for ubiquitination", "for ubiquitination by", "ubiquitination by nedd4l", "by nedd4l and", "nedd4l and smurf", "and smurf ubiquitin", "smurf ubiquitin ligases.", "ubiquitin ligases. nedd4l", "ligases. nedd4l ubiquitinates", "nedd4l ubiquitinates smad2/3", "ubiquitinates smad2/3 and", "smad2/3 and targets", "and targets smad2/3:smad4", "targets smad2/3:smad4 heterotrimer", "smad2/3:smad4 heterotrimer for", "heterotrimer for degradation", "degradation gao", "gao et al.", "al. 2009 .", "2009 . smurf2", ". smurf2 monoubiquitinates", "smurf2 monoubiquitinates smad2/3", "smad2/3 leading", "leading to disruption", "to disruption of", "disruption of smad2/3:smad4", "of smad2/3:smad4 complexes", "complexes tang", "tang et al.", "et al. 2011", "al. 2011 .", "2011 .
transcriptional", ".
transcriptional repressors", "
transcriptional repressors tgif1", "repressors tgif1 and", "tgif1 and tgif2", "and tgif2 bind", "tgif2 bind smad2/3:smad4", "bind smad2/3:smad4 complexes", "smad2/3:smad4 complexes and", "complexes and inhibit", "and inhibit smad", "inhibit smad mediated", "smad mediated transcription", "mediated transcription by", "transcription by recruitment", "by recruitment of", "recruitment of histone", "of histone deacetylase", "histone deacetylase hdac1", "deacetylase hdac1 to", "hdac1 to smad", "elements wotton", "wotton et al.", "1999 melhuish", "melhuish et al.", "al. 2001 .
parp1", "2001 .
parp1 can", ".
parp1 can attach", "can attach poly", "attach poly adp", "poly adp ribosyl", "adp ribosyl chains", "ribosyl chains to", "chains to smad3", "to smad3 and", "smad3 and smad4", "and smad4 within", "smad4 within smad2/3:smad4", "within smad2/3:smad4 heterotrimers.", "smad2/3:smad4 heterotrimers. parylated", "heterotrimers. parylated smad2/3:smad4", "parylated smad2/3:smad4 complexes", "smad2/3:smad4 complexes are", "complexes are unable", "are unable to", "unable to bind", "to bind smad", "bind smad binding", "smad binding dna", "binding dna elements", "elements sbes", "lonn et al.", "et al. 2010", "al. 2010 .", "2010 .
phosphorylated", ".
phosphorylated smad2", "
phosphorylated smad2 and", "and smad3 can", "smad3 can be", "can be dephosphorylated", "be dephosphorylated by", "dephosphorylated by ppm1a", "by ppm1a protein", "ppm1a protein phosphatase", "phosphatase leading", "leading to dissociation", "to dissociation of", "dissociation of smad2/3", "of smad2/3 complexes", "smad2/3 complexes and", "complexes and translocation", "and translocation of", "translocation of unphosphorylated", "of unphosphorylated smad2/3", "unphosphorylated smad2/3 to", "smad2/3 to the", "to the cytosol", "cytosol lin", "lin et al.", "et al. 2006", "al. 2006 .", "transcriptional activity of smad2/3:smad4", "activity of smad2/3:smad4 heterotrimer", "of smad2/3:smad4 heterotrimer can", "smad2/3:smad4 heterotrimer can be", "heterotrimer can be inhibited", "can be inhibited by", "be inhibited by formation", "inhibited by formation of", "by formation of a", "formation of a complex", "of a complex with", "a complex with ski", "complex with ski or", "with ski or skil", "or skil sno", "sno where", "where ski or skil", "ski or skil recruit", "or skil recruit ncor", "skil recruit ncor and", "recruit ncor and possibly", "ncor and possibly other", "and possibly other transcriptional", "possibly other transcriptional repressors", "other transcriptional repressors to", "transcriptional repressors to smad", "repressors to smad binding", "to smad binding promoter", "smad binding promoter elements", "promoter elements sun", "elements sun et", "sun et al. 1999", "al. 1999 luo", "1999 luo et", "luo et al. 1999", "al. 1999 strochein", "1999 strochein et", "strochein et al. 1999", "et al. 1999 .", "al. 1999 . higher", "1999 . higher levels", ". higher levels of", "higher levels of phosphorylated", "levels of phosphorylated smad2", "of phosphorylated smad2 and", "phosphorylated smad2 and smad3", "and smad3 however", "however may target", "may target ski and", "target ski and skil", "ski and skil for", "and skil for degradation", "for degradation strochein", "degradation strochein et", "al. 1999 sun", "1999 sun et", "et al. 1999 pnas", "1999 pnas bonni", "pnas bonni et", "bonni et al. 2001", "al. 2001 through", "2001 through recruitment", "through recruitment of smurf2", "of smurf2 bonni", "smurf2 bonni et", "al. 2001 or", "2001 or rnf111", "or rnf111 i.e. arkadia", "i.e. arkadia levy", "arkadia levy et", "levy et al. 2007", "al. 2007 ubiquitin", "2007 ubiquitin ligases", "ubiquitin ligases to ski/skil", "ligases to ski/skil by", "to ski/skil by smad2/3.", "ski/skil by smad2/3. therefore", "by smad2/3. therefore the", "smad2/3. therefore the ratio", "therefore the ratio of", "the ratio of smad2/3", "ratio of smad2/3 and", "of smad2/3 and ski/skil", "smad2/3 and ski/skil determines", "and ski/skil determines the", "ski/skil determines the outcome:", "determines the outcome: inhibition", "the outcome: inhibition of", "outcome: inhibition of smad2/3:smad4", "inhibition of smad2/3:smad4 mediated", "of smad2/3:smad4 mediated transcription", "smad2/3:smad4 mediated transcription or", "mediated transcription or degradation", "transcription or degradation of", "or degradation of ski/skil.", "degradation of ski/skil. ski", "of ski/skil. ski and", "ski/skil. ski and skil", "ski and skil are", "and skil are overexpressed", "skil are overexpressed in", "are overexpressed in various", "overexpressed in various cancer", "in various cancer types", "various cancer types and", "cancer types and their", "types and their oncogenic", "and their oncogenic effect", "their oncogenic effect is", "oncogenic effect is connected", "effect is connected with", "is connected with their", "connected with their ability", "with their ability to", "their ability to inhibit", "ability to inhibit signaling", "to inhibit signaling by", "inhibit signaling by tgf", "signaling by tgf beta", "by tgf beta receptor", "tgf beta receptor complex.", "beta receptor complex.
smad4", "receptor complex.
smad4 can", "complex.
smad4 can be", "
smad4 can be monoubiquitinated", "can be monoubiquitinated by", "be monoubiquitinated by a", "monoubiquitinated by a nuclear", "by a nuclear ubiquitin", "a nuclear ubiquitin ligase", "nuclear ubiquitin ligase trim33", "ligase trim33 ecto", "ectodermin tif1 gamma", "tif1 gamma . monoubiquitination", "gamma . monoubiquitination of", ". monoubiquitination of smad4", "monoubiquitination of smad4 disrupts", "of smad4 disrupts smad2/3:smad4", "smad4 disrupts smad2/3:smad4 heterotrimers", "disrupts smad2/3:smad4 heterotrimers and", "smad2/3:smad4 heterotrimers and leads", "heterotrimers and leads to", "and leads to smad4", "leads to smad4 translocation", "to smad4 translocation to", "smad4 translocation to the", "translocation to the cytosol.", "to the cytosol. in", "the cytosol. in the", "cytosol. in the cytosol", "the cytosol smad4", "cytosol smad4 can", "smad4 can be deubiquitinated", "can be deubiquitinated by", "be deubiquitinated by usp9x", "by usp9x fam", "fam reversing", "reversing trim33 mediated negative", "trim33 mediated negative regulation", "negative regulation dupont", "regulation dupont et", "dupont et al. 2009", "et al. 2009 .
phosphorylation", "al. 2009 .
phosphorylation of", "2009 .
phosphorylation of the", ".
phosphorylation of the linker", "of the linker region", "the linker region of", "linker region of smad2", "region of smad2 and", "of smad2 and smad3", "smad2 and smad3 by", "and smad3 by cdk8", "smad3 by cdk8 or", "by cdk8 or cdk9", "cdk8 or cdk9 primes", "or cdk9 primes smad2/3:smad4", "cdk9 primes smad2/3:smad4 complex", "primes smad2/3:smad4 complex for", "smad2/3:smad4 complex for ubiquitination", "complex for ubiquitination by", "for ubiquitination by nedd4l", "ubiquitination by nedd4l and", "by nedd4l and smurf", "nedd4l and smurf ubiquitin", "and smurf ubiquitin ligases.", "smurf ubiquitin ligases. nedd4l", "ubiquitin ligases. nedd4l ubiquitinates", "ligases. nedd4l ubiquitinates smad2/3", "nedd4l ubiquitinates smad2/3 and", "ubiquitinates smad2/3 and targets", "smad2/3 and targets smad2/3:smad4", "and targets smad2/3:smad4 heterotrimer", "targets smad2/3:smad4 heterotrimer for", "smad2/3:smad4 heterotrimer for degradation", "for degradation gao", "degradation gao et", "gao et al. 2009", "et al. 2009 .", "al. 2009 . smurf2", "2009 . smurf2 monoubiquitinates", ". smurf2 monoubiquitinates smad2/3", "monoubiquitinates smad2/3 leading", "smad2/3 leading to", "leading to disruption of", "to disruption of smad2/3:smad4", "disruption of smad2/3:smad4 complexes", "smad2/3:smad4 complexes tang", "complexes tang et", "tang et al. 2011", "et al. 2011 .", "al. 2011 .
transcriptional", "2011 .
transcriptional repressors", ".
transcriptional repressors tgif1", "
transcriptional repressors tgif1 and", "repressors tgif1 and tgif2", "tgif1 and tgif2 bind", "and tgif2 bind smad2/3:smad4", "tgif2 bind smad2/3:smad4 complexes", "bind smad2/3:smad4 complexes and", "smad2/3:smad4 complexes and inhibit", "complexes and inhibit smad", "and inhibit smad mediated", "inhibit smad mediated transcription", "smad mediated transcription by", "mediated transcription by recruitment", "transcription by recruitment of", "by recruitment of histone", "recruitment of histone deacetylase", "of histone deacetylase hdac1", "histone deacetylase hdac1 to", "deacetylase hdac1 to smad", "hdac1 to smad binding", "promoter elements wotton", "elements wotton et", "wotton et al. 1999", "al. 1999 melhuish", "1999 melhuish et", "melhuish et al. 2001", "et al. 2001 .
parp1", "al. 2001 .
parp1 can", "2001 .
parp1 can attach", ".
parp1 can attach poly", "can attach poly adp", "attach poly adp ribosyl", "poly adp ribosyl chains", "adp ribosyl chains to", "ribosyl chains to smad3", "chains to smad3 and", "to smad3 and smad4", "smad3 and smad4 within", "and smad4 within smad2/3:smad4", "smad4 within smad2/3:smad4 heterotrimers.", "within smad2/3:smad4 heterotrimers. parylated", "smad2/3:smad4 heterotrimers. parylated smad2/3:smad4", "heterotrimers. parylated smad2/3:smad4 complexes", "parylated smad2/3:smad4 complexes are", "smad2/3:smad4 complexes are unable", "complexes are unable to", "are unable to bind", "unable to bind smad", "to bind smad binding", "bind smad binding dna", "smad binding dna elements", "dna elements sbes", "sbes lonn", "lonn et al. 2010", "et al. 2010 .", "al. 2010 .
phosphorylated", "2010 .
phosphorylated smad2", ".
phosphorylated smad2 and", "
phosphorylated smad2 and smad3", "smad2 and smad3 can", "and smad3 can be", "smad3 can be dephosphorylated", "can be dephosphorylated by", "be dephosphorylated by ppm1a", "dephosphorylated by ppm1a protein", "by ppm1a protein phosphatase", "protein phosphatase leading", "phosphatase leading to", "leading to dissociation of", "to dissociation of smad2/3", "dissociation of smad2/3 complexes", "of smad2/3 complexes and", "smad2/3 complexes and translocation", "complexes and translocation of", "and translocation of unphosphorylated", "translocation of unphosphorylated smad2/3", "of unphosphorylated smad2/3 to", "unphosphorylated smad2/3 to the", "smad2/3 to the cytosol", "the cytosol lin", "cytosol lin et", "lin et al. 2006", "et al. 2006 .", "transcriptional activity of smad2/3:smad4 heterotrimer", "activity of smad2/3:smad4 heterotrimer can", "of smad2/3:smad4 heterotrimer can be", "smad2/3:smad4 heterotrimer can be inhibited", "heterotrimer can be inhibited by", "can be inhibited by formation", "be inhibited by formation of", "inhibited by formation of a", "by formation of a complex", "formation of a complex with", "of a complex with ski", "a complex with ski or", "complex with ski or skil", "ski or skil sno", "sno where ski", "where ski or skil recruit", "ski or skil recruit ncor", "or skil recruit ncor and", "skil recruit ncor and possibly", "recruit ncor and possibly other", "ncor and possibly other transcriptional", "and possibly other transcriptional repressors", "possibly other transcriptional repressors to", "other transcriptional repressors to smad", "transcriptional repressors to smad binding", "repressors to smad binding promoter", "to smad binding promoter elements", "binding promoter elements sun", "promoter elements sun et", "elements sun et al.", "et al. 1999 luo", "al. 1999 luo et", "1999 luo et al.", "et al. 1999 strochein", "al. 1999 strochein et", "1999 strochein et al.", "strochein et al. 1999 .", "et al. 1999 . higher", "al. 1999 . higher levels", "1999 . higher levels of", ". higher levels of phosphorylated", "higher levels of phosphorylated smad2", "levels of phosphorylated smad2 and", "of phosphorylated smad2 and smad3", "smad2 and smad3 however", "smad3 however may", "however may target ski", "may target ski and skil", "target ski and skil for", "ski and skil for degradation", "skil for degradation strochein", "for degradation strochein et", "degradation strochein et al.", "et al. 1999 sun", "al. 1999 sun et", "1999 sun et al.", "sun et al. 1999 pnas", "al. 1999 pnas bonni", "1999 pnas bonni et", "pnas bonni et al.", "et al. 2001 through", "al. 2001 through recruitment", "2001 through recruitment of", "recruitment of smurf2 bonni", "of smurf2 bonni et", "smurf2 bonni et al.", "et al. 2001 or", "al. 2001 or rnf111", "2001 or rnf111 i.e.", "rnf111 i.e. arkadia levy", "i.e. arkadia levy et", "arkadia levy et al.", "et al. 2007 ubiquitin", "al. 2007 ubiquitin ligases", "2007 ubiquitin ligases to", "ubiquitin ligases to ski/skil by", "ligases to ski/skil by smad2/3.", "to ski/skil by smad2/3. therefore", "ski/skil by smad2/3. therefore the", "by smad2/3. therefore the ratio", "smad2/3. therefore the ratio of", "therefore the ratio of smad2/3", "the ratio of smad2/3 and", "ratio of smad2/3 and ski/skil", "of smad2/3 and ski/skil determines", "smad2/3 and ski/skil determines the", "and ski/skil determines the outcome:", "ski/skil determines the outcome: inhibition", "determines the outcome: inhibition of", "the outcome: inhibition of smad2/3:smad4", "outcome: inhibition of smad2/3:smad4 mediated", "inhibition of smad2/3:smad4 mediated transcription", "of smad2/3:smad4 mediated transcription or", "smad2/3:smad4 mediated transcription or degradation", "mediated transcription or degradation of", "transcription or degradation of ski/skil.", "or degradation of ski/skil. ski", "degradation of ski/skil. ski and", "of ski/skil. ski and skil", "ski/skil. ski and skil are", "ski and skil are overexpressed", "and skil are overexpressed in", "skil are overexpressed in various", "are overexpressed in various cancer", "overexpressed in various cancer types", "in various cancer types and", "various cancer types and their", "cancer types and their oncogenic", "types and their oncogenic effect", "and their oncogenic effect is", "their oncogenic effect is connected", "oncogenic effect is connected with", "effect is connected with their", "is connected with their ability", "connected with their ability to", "with their ability to inhibit", "their ability to inhibit signaling", "ability to inhibit signaling by", "to inhibit signaling by tgf", "inhibit signaling by tgf beta", "signaling by tgf beta receptor", "by tgf beta receptor complex.", "tgf beta receptor complex.
smad4", "beta receptor complex.
smad4 can", "receptor complex.
smad4 can be", "complex.
smad4 can be monoubiquitinated", "
smad4 can be monoubiquitinated by", "can be monoubiquitinated by a", "be monoubiquitinated by a nuclear", "monoubiquitinated by a nuclear ubiquitin", "by a nuclear ubiquitin ligase", "a nuclear ubiquitin ligase trim33", "ubiquitin ligase trim33 ecto", "trim33 ecto ectodermin", "ecto ectodermin tif1", "ectodermin tif1 gamma .", "tif1 gamma . monoubiquitination of", "gamma . monoubiquitination of smad4", ". monoubiquitination of smad4 disrupts", "monoubiquitination of smad4 disrupts smad2/3:smad4", "of smad4 disrupts smad2/3:smad4 heterotrimers", "smad4 disrupts smad2/3:smad4 heterotrimers and", "disrupts smad2/3:smad4 heterotrimers and leads", "smad2/3:smad4 heterotrimers and leads to", "heterotrimers and leads to smad4", "and leads to smad4 translocation", "leads to smad4 translocation to", "to smad4 translocation to the", "smad4 translocation to the cytosol.", "translocation to the cytosol. in", "to the cytosol. in the", "the cytosol. in the cytosol", "in the cytosol smad4", "the cytosol smad4 can", "cytosol smad4 can be", "smad4 can be deubiquitinated by", "can be deubiquitinated by usp9x", "deubiquitinated by usp9x fam", "fam reversing trim33", "reversing trim33 mediated negative regulation", "mediated negative regulation dupont", "negative regulation dupont et", "regulation dupont et al.", "dupont et al. 2009 .
phosphorylation", "et al. 2009 .
phosphorylation of", "al. 2009 .
phosphorylation of the", "2009 .
phosphorylation of the linker", ".
phosphorylation of the linker region", "of the linker region of", "the linker region of smad2", "linker region of smad2 and", "region of smad2 and smad3", "of smad2 and smad3 by", "smad2 and smad3 by cdk8", "and smad3 by cdk8 or", "smad3 by cdk8 or cdk9", "by cdk8 or cdk9 primes", "cdk8 or cdk9 primes smad2/3:smad4", "or cdk9 primes smad2/3:smad4 complex", "cdk9 primes smad2/3:smad4 complex for", "primes smad2/3:smad4 complex for ubiquitination", "smad2/3:smad4 complex for ubiquitination by", "complex for ubiquitination by nedd4l", "for ubiquitination by nedd4l and", "ubiquitination by nedd4l and smurf", "by nedd4l and smurf ubiquitin", "nedd4l and smurf ubiquitin ligases.", "and smurf ubiquitin ligases. nedd4l", "smurf ubiquitin ligases. nedd4l ubiquitinates", "ubiquitin ligases. nedd4l ubiquitinates smad2/3", "ligases. nedd4l ubiquitinates smad2/3 and", "nedd4l ubiquitinates smad2/3 and targets", "ubiquitinates smad2/3 and targets smad2/3:smad4", "smad2/3 and targets smad2/3:smad4 heterotrimer", "and targets smad2/3:smad4 heterotrimer for", "targets smad2/3:smad4 heterotrimer for degradation", "heterotrimer for degradation gao", "for degradation gao et", "degradation gao et al.", "gao et al. 2009 .", "et al. 2009 . smurf2", "al. 2009 . smurf2 monoubiquitinates", "2009 . smurf2 monoubiquitinates smad2/3", "smurf2 monoubiquitinates smad2/3 leading", "monoubiquitinates smad2/3 leading to", "smad2/3 leading to disruption", "leading to disruption of smad2/3:smad4", "to disruption of smad2/3:smad4 complexes", "of smad2/3:smad4 complexes tang", "smad2/3:smad4 complexes tang et", "complexes tang et al.", "tang et al. 2011 .", "et al. 2011 .
transcriptional", "al. 2011 .
transcriptional repressors", "2011 .
transcriptional repressors tgif1", ".
transcriptional repressors tgif1 and", "
transcriptional repressors tgif1 and tgif2", "repressors tgif1 and tgif2 bind", "tgif1 and tgif2 bind smad2/3:smad4", "and tgif2 bind smad2/3:smad4 complexes", "tgif2 bind smad2/3:smad4 complexes and", "bind smad2/3:smad4 complexes and inhibit", "smad2/3:smad4 complexes and inhibit smad", "complexes and inhibit smad mediated", "and inhibit smad mediated transcription", "inhibit smad mediated transcription by", "smad mediated transcription by recruitment", "mediated transcription by recruitment of", "transcription by recruitment of histone", "by recruitment of histone deacetylase", "recruitment of histone deacetylase hdac1", "of histone deacetylase hdac1 to", "histone deacetylase hdac1 to smad", "deacetylase hdac1 to smad binding", "hdac1 to smad binding promoter", "binding promoter elements wotton", "promoter elements wotton et", "elements wotton et al.", "et al. 1999 melhuish", "al. 1999 melhuish et", "1999 melhuish et al.", "melhuish et al. 2001 .
parp1", "et al. 2001 .
parp1 can", "al. 2001 .
parp1 can attach", "2001 .
parp1 can attach poly", ".
parp1 can attach poly adp", "can attach poly adp ribosyl", "attach poly adp ribosyl chains", "poly adp ribosyl chains to", "adp ribosyl chains to smad3", "ribosyl chains to smad3 and", "chains to smad3 and smad4", "to smad3 and smad4 within", "smad3 and smad4 within smad2/3:smad4", "and smad4 within smad2/3:smad4 heterotrimers.", "smad4 within smad2/3:smad4 heterotrimers. parylated", "within smad2/3:smad4 heterotrimers. parylated smad2/3:smad4", "smad2/3:smad4 heterotrimers. parylated smad2/3:smad4 complexes", "heterotrimers. parylated smad2/3:smad4 complexes are", "parylated smad2/3:smad4 complexes are unable", "smad2/3:smad4 complexes are unable to", "complexes are unable to bind", "are unable to bind smad", "unable to bind smad binding", "to bind smad binding dna", "bind smad binding dna elements", "binding dna elements sbes", "sbes lonn et", "lonn et al. 2010 .", "et al. 2010 .
phosphorylated", "al. 2010 .
phosphorylated smad2", "2010 .
phosphorylated smad2 and", ".
phosphorylated smad2 and smad3", "
phosphorylated smad2 and smad3 can", "smad2 and smad3 can be", "and smad3 can be dephosphorylated", "smad3 can be dephosphorylated by", "can be dephosphorylated by ppm1a", "be dephosphorylated by ppm1a protein", "dephosphorylated by ppm1a protein phosphatase", "ppm1a protein phosphatase leading", "protein phosphatase leading to", "phosphatase leading to dissociation", "leading to dissociation of smad2/3", "to dissociation of smad2/3 complexes", "dissociation of smad2/3 complexes and", "of smad2/3 complexes and translocation", "smad2/3 complexes and translocation of", "complexes and translocation of unphosphorylated", "and translocation of unphosphorylated smad2/3", "translocation of unphosphorylated smad2/3 to", "of unphosphorylated smad2/3 to the", "unphosphorylated smad2/3 to the cytosol", "to the cytosol lin", "the cytosol lin et", "cytosol lin et al.", "lin et al. 2006 ." ] }, { "record_id": "GLY_000594_1_889", "filename": "human_protein_pathways_reactome", "fieldtype": "id", 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"activation dufresne et al.", "et al. 2006 liebmann", "al. 2006 liebmann 2011", "2006 liebmann 2011 ." ] }, { "record_id": "GLY_000594_1_890", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2187335", "r hsa", "hsa 2187335", "r hsa 2187335" ] }, { "record_id": "GLY_000594_1_890", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "the retinoid", "retinoid cycle", "cycle in", "in cones", "daylight vision", "the retinoid cycle", "retinoid cycle in", "cycle in cones", "cones daylight", "the retinoid cycle in", "retinoid cycle in cones", "in cones daylight", "cones daylight vision", "the retinoid cycle in cones", "cycle in cones daylight", "in cones daylight vision", "rods and", "and cones", "cones share", "share the", "the same", "same mechanism", "mechanism for", "for the", "the phototransduction", "phototransduction process", "process but", "but perform", "perform functionally", "functionally different", "different roles.", "roles. although", "although cone", "cone photoreceptors", "photoreceptors make", "make up", "up around", "around 5%", "5% of", "of all", "all photoreceptor", "photoreceptor cells", "cells and", "and are", "are outnumbered", "outnumbered 20", "20 to", "to 1", "1 by", "by rod", "rod photoreceptors", "they mediate", "mediate daylight", "vision in", "in the", "the human", "human eye", "eye whereas", "whereas rods", "rods mediate", "mediate twilight", "twilight vision.", "vision. also", "cones are", "are around", "around 100", "100 times", "times less", "less light", "light sensitive", "sensitive than", "than rods", "rods thereby", "thereby depriving", "depriving us", "us of", "of colour", "colour vision", "in dark", "dark conditions", "conditions in", "in which", "which cones", "cones cannot", "cannot function.", "function. rod", "rod function", "function saturates", "saturates in", "in even", "even moderate", "moderate amounts", "amounts of", "of light", "light whereas", "whereas cones", "cones can", "can adjust", "adjust to", "to even", "even very", "very bright", "bright light", "light conditions", "a process", "process called", "called light", "light adaptation.", "adaptation. in", "in bright", "bright conditions", "rods can", "can take", "take up", "up to", "to one", "one hour", "hour to", "to regain", "regain their", "their sensitivity", "sensitivity whereas", "can recover", "recover in", "in a", "a few", "few minutes", "called dark", "dark adaptation", "adaptation and", "and which", "which allows", "allows us", "us to", "to retain", "retain visual", "visual perception", "perception in", "in changing", "changing light", "light conditions.

cone", "conditions.

cone cells", "cells express", "express three", "three types", "types of", "of opsin", "opsin which", "which allow", "allow colour", "colour discrimination.", "discrimination. long", "long wavelength", "wavelength sensitive", "sensitive opsin", "detects red", "short wavelength", "detects blue", "and medium", "medium wavelength", "detects green", "green regions", "regions of", "of the", "the light", "light spectrum.

in", "spectrum.

in the", "the canonical", "canonical retinoid", "the visual", "visual chromophore", "chromophore is", "is regenerated", "regenerated in", "in reactions", "reactions involving", "involving the", "the rod", "rod outer", "outer segments", "and the", "the retinal", "retinal pigment", "pigment epithelium", "rpe .", ". for", "for cones", "chromophore recycling", "recycling is", "is independent", "independent of", "the rpe", "rpe and", "and instead", "instead involves", "involves muller", "muller cells", "cells in", "the retina", "retina which", "which supply", "supply the", "the chromophore", "chromophore selectively", "selectively to", "to cones.", "cones. the", "the molecular", "molecular steps", "steps of", "the cone", "cone retinoid", "cycle are", "are outlined", "outlined in", "in this", "this section.", "section. the", "the ability", "ability of", "of cones", "cones to", "to react", "react to", "to bright", "bright and", "and differing", "differing light", "conditions means", "means it", "it has", "has to", "to regenerate", "regenerate the", "chromophore much", "much quicker", "quicker than", "than rods.", "rods. all", "all trans", "trans retinol", "released from", "from cone", "cone outer", "segments is", "is taken", "taken up", "up by", "by muller", "cells where", "where it", "it is", "is directly", "directly isomerized", "isomerized back", "back to", "to 11", "11 cis", "cis retinol", "then esterified", "esterified by", "by lrat.", "lrat. when", "when required", "these 11", "cis retinyl", "retinyl esters", "esters can", "can be", "be hydrolysed", "hydrolysed by", "by 11", "cis re", "re hydrolases", "hydrolases back", "to 11crol", "11crol then", "then oxidised", "oxidised in", "cone photoreceptor", "photoreceptor cell", "cell to", "regenerate 11", "cis retinal", "see reviews", "reviews von", "von lintig", "lintig 2012", "wang &", "& kefalov", "kefalov 2011", "kefalov 2012", "wolf 2004", "2004 .", "rods and cones", "and cones share", "cones share the", "share the same", "the same mechanism", "same mechanism for", "mechanism for the", "for the phototransduction", "the phototransduction process", "phototransduction process but", "process but perform", "but perform functionally", "perform functionally different", "functionally different roles.", "different roles. although", "roles. although cone", "although cone photoreceptors", "cone photoreceptors make", "photoreceptors make up", "make up around", "up around 5%", "around 5% of", "5% of all", "of all photoreceptor", "all photoreceptor cells", "photoreceptor cells and", "cells and are", "and are outnumbered", "are outnumbered 20", "outnumbered 20 to", "20 to 1", "to 1 by", "1 by rod", "by rod photoreceptors", "photoreceptors they", "they mediate daylight", "mediate daylight vision", "daylight vision in", "vision in the", "in the human", "the human eye", "human eye whereas", "eye whereas rods", "whereas rods mediate", "rods mediate twilight", "mediate twilight vision.", "twilight vision. also", "also cones", "cones are around", "are around 100", "around 100 times", "100 times less", "times less light", "less light sensitive", "light sensitive than", "sensitive than rods", "than rods thereby", "rods thereby depriving", "thereby depriving us", "depriving us of", "us of colour", "of colour vision", "colour vision in", "vision in dark", "in dark conditions", "dark conditions in", "conditions in which", "in which cones", "which cones cannot", "cones cannot function.", "cannot function. rod", "function. rod function", "rod function saturates", "function saturates in", "saturates in even", "in even moderate", "even moderate amounts", "moderate amounts of", "amounts of light", "of light whereas", "light whereas cones", "whereas cones can", "cones can adjust", "can adjust to", "adjust to even", "to even very", "even very bright", "very bright light", "bright light conditions", "conditions a", "a process called", "process called light", "called light adaptation.", "light adaptation. in", "adaptation. in bright", "in bright conditions", "conditions rods", "rods can take", "can take up", "take up to", "up to one", "to one hour", "one hour to", "hour to regain", "to regain their", "regain their sensitivity", "their sensitivity whereas", "sensitivity whereas cones", "cones can recover", "can recover in", "recover in a", "in a few", "a few minutes", "minutes a", "process called dark", "called dark adaptation", "dark adaptation and", "adaptation and which", "and which allows", "which allows us", "allows us to", "us to retain", "to retain visual", "retain visual perception", "visual perception in", "perception in changing", "in changing light", "changing light conditions.

cone", "light conditions.

cone cells", "conditions.

cone cells express", "cells express three", "express three types", "three types of", "types of opsin", "of opsin which", "opsin which allow", "which allow colour", "allow colour discrimination.", "colour discrimination. long", "discrimination. long wavelength", "long wavelength sensitive", "wavelength sensitive opsin", "opsin opn1lw", "opn1lw detects", "short wavelength sensitive", "opsin opn1sw", "opn1sw detects", "blue and", "and medium wavelength", "medium wavelength sensitive", "opsin opn1mw", "opn1mw detects", "detects green regions", "green regions of", "regions of the", "of the light", "the light spectrum.

in", "light spectrum.

in the", "spectrum.

in the canonical", "the canonical retinoid", "retinoid visual", "visual cycle", "cycle the", "the visual chromophore", "visual chromophore is", "chromophore is regenerated", "is regenerated in", "regenerated in reactions", "in reactions involving", "reactions involving the", "involving the rod", "the rod outer", "rod outer segments", "segments ros", "ros and", "and the retinal", "the retinal pigment", "retinal pigment epithelium", "epithelium rpe", "rpe . for", ". for cones", "cones chromophore", "chromophore recycling is", "recycling is independent", "is independent of", "independent of the", "of the rpe", "the rpe and", "rpe and instead", "and instead involves", "instead involves muller", "involves muller cells", "muller cells in", "cells in the", "in the retina", "the retina which", "retina which supply", "which supply the", "supply the chromophore", "the chromophore selectively", "chromophore selectively to", "selectively to cones.", "to cones. the", "cones. the molecular", "the molecular steps", "molecular steps of", "steps of the", "of the cone", "the cone retinoid", "cycle are outlined", "are outlined in", "outlined in this", "in this section.", "this section. the", "section. the ability", "the ability of", "ability of cones", "of cones to", "cones to react", "to react to", "react to bright", "to bright and", "bright and differing", "and differing light", "differing light conditions", "light conditions means", "conditions means it", "means it has", "it has to", "has to regenerate", "to regenerate the", "regenerate the chromophore", "the chromophore much", "chromophore much quicker", "much quicker than", "quicker than rods.", "than rods. all", "rods. all trans", "all trans retinol", "retinol atrol", "atrol released", "released from cone", "from cone outer", "cone outer segments", "outer segments is", "segments is taken", "is taken up", "taken up by", "up by muller", "by muller cells", "muller cells where", "cells where it", "where it is", "it is directly", "is directly isomerized", "directly isomerized back", "isomerized back to", "back to 11", "to 11 cis", "11 cis retinol", "retinol 11crol", "then esterified by", "esterified by lrat.", "by lrat. when", "lrat. when required", "required these", "these 11 cis", "11 cis retinyl", "cis retinyl esters", "retinyl esters can", "esters can be", "can be hydrolysed", "be hydrolysed by", "hydrolysed by 11", "by 11 cis", "11 cis re", "cis re hydrolases", "re hydrolases back", "hydrolases back to", "back to 11crol", "to 11crol then", "11crol then oxidised", "then oxidised in", "oxidised in the", "in the cone", "the cone photoreceptor", "cone photoreceptor cell", "photoreceptor cell to", "cell to regenerate", "to regenerate 11", "regenerate 11 cis", "11 cis retinal", "retinal 11cral", "chromophore see", "see reviews von", "reviews von lintig", "von lintig 2012", "2012 wang", "wang & kefalov", "& kefalov 2011", "2011 kefalov", "2012 wolf", "wolf 2004 .", "rods and cones share", "and cones share the", 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"cones can recover in", "can recover in a", "recover in a few", "in a few minutes", "few minutes a", "minutes a process", "a process called dark", "process called dark adaptation", "called dark adaptation and", "dark adaptation and which", "adaptation and which allows", "and which allows us", "which allows us to", "allows us to retain", "us to retain visual", "to retain visual perception", "retain visual perception in", "visual perception in changing", "perception in changing light", "in changing light conditions.

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the chromophore", "supply the chromophore selectively", "the chromophore selectively to", "chromophore selectively to cones.", "selectively to cones. the", "to cones. the molecular", "cones. the molecular steps", "the molecular steps of", "molecular steps of the", "steps of the cone", "of the cone retinoid", "cone retinoid visual", "visual cycle are", "cycle are outlined in", "are outlined in this", "outlined in this section.", "in this section. the", "this section. the ability", "section. the ability of", "the ability of cones", "ability of cones to", "of cones to react", "cones to react to", "to react to bright", "react to bright and", "to bright and differing", "bright and differing light", "and differing light conditions", "differing light conditions means", "light conditions means it", "conditions means it has", "means it has to", "it has to regenerate", "has to regenerate the", "to regenerate the chromophore", "regenerate the chromophore much", "the chromophore much quicker", "chromophore much quicker than", "much quicker than rods.", "quicker than rods. all", "than rods. all trans", "rods. all trans retinol", "trans retinol atrol", "atrol released from", "released from cone outer", "from cone outer segments", "cone outer segments is", "outer segments is taken", "segments is taken up", "is taken up by", "taken up by muller", "up by muller cells", "by muller cells where", "muller cells where it", "cells where it is", "where it is directly", "it is directly isomerized", "is directly isomerized back", "directly isomerized back to", "isomerized back to 11", "back to 11 cis", "to 11 cis retinol", "cis retinol 11crol", "11crol then esterified", "then esterified by lrat.", "esterified by lrat. when", "by lrat. when required", "when required these", "required these 11", "these 11 cis retinyl", "11 cis retinyl esters", "cis retinyl esters can", "retinyl esters can be", "esters can be hydrolysed", "can be hydrolysed by", "be hydrolysed by 11", "hydrolysed by 11 cis", "by 11 cis re", "11 cis re hydrolases", "cis re hydrolases back", "re hydrolases back to", "hydrolases back to 11crol", "back to 11crol then", "to 11crol then oxidised", "11crol then oxidised in", "then oxidised in the", "oxidised in the cone", "in the cone photoreceptor", "the cone photoreceptor cell", "cone photoreceptor cell to", "photoreceptor cell to regenerate", "cell to regenerate 11", "to regenerate 11 cis", "regenerate 11 cis retinal", "cis retinal 11cral", "11cral the", "visual chromophore see", "chromophore see reviews", "see reviews von lintig", "reviews von lintig 2012", "lintig 2012 wang", "2012 wang &", "wang & kefalov 2011", "kefalov 2011 kefalov", "2011 kefalov 2012", "kefalov 2012 wolf", "2012 wolf 2004", "rods and cones share the", "and cones share the same", "cones share the same mechanism", "share the same mechanism for", "the same mechanism for the", "same mechanism for the phototransduction", "mechanism for the phototransduction process", "for the phototransduction process but", "the phototransduction process but perform", "phototransduction process but perform functionally", "process but perform functionally different", "but perform functionally different roles.", "perform functionally different roles. although", "functionally different roles. although cone", "different roles. although cone photoreceptors", "roles. although cone photoreceptors make", "although cone photoreceptors make up", "cone photoreceptors make up around", "photoreceptors make up around 5%", "make up around 5% of", "up around 5% of all", "around 5% of all photoreceptor", "5% of all photoreceptor cells", "of all photoreceptor cells and", "all photoreceptor cells and are", "photoreceptor cells and are outnumbered", "cells and are outnumbered 20", "and are outnumbered 20 to", "are outnumbered 20 to 1", "outnumbered 20 to 1 by", "20 to 1 by rod", "to 1 by rod photoreceptors", "by rod photoreceptors they", "rod photoreceptors they mediate", "photoreceptors they mediate daylight", "they mediate daylight vision in", "mediate daylight vision in the", "daylight vision in the human", "vision in the human eye", "in the human eye whereas", "the human eye whereas rods", "human eye whereas rods mediate", "eye whereas rods mediate twilight", "whereas rods mediate twilight vision.", "rods mediate twilight vision. also", "twilight vision. also cones", "vision. also cones are", "also cones are around", "cones are around 100 times", "are around 100 times less", "around 100 times less light", "100 times less light sensitive", "times less light sensitive than", "less light sensitive than rods", "light sensitive than rods thereby", "sensitive than rods thereby depriving", "than rods thereby depriving us", "rods thereby depriving us of", "thereby depriving us of colour", "depriving us of colour vision", "us of colour vision in", "of colour vision in dark", "colour vision in dark conditions", "vision in dark conditions in", "in dark conditions in which", "dark conditions in which cones", "conditions in which cones cannot", "in which cones cannot function.", "which cones cannot function. rod", "cones cannot function. rod function", "cannot function. rod function saturates", "function. rod function saturates in", "rod function saturates in even", "function saturates in even moderate", "saturates in even moderate amounts", "in even moderate amounts of", "even moderate amounts of light", "moderate amounts of light whereas", "amounts of light whereas cones", "of light whereas cones can", "light whereas cones can adjust", "whereas cones can adjust to", "cones can adjust to even", "can adjust to even very", "adjust to even very bright", "to even very bright light", "even very bright light conditions", "bright light conditions a", "light conditions a process", "conditions a process called", "a process called light adaptation.", "process called light adaptation. in", "called light adaptation. in bright", "light adaptation. in bright conditions", "in bright conditions rods", "bright conditions rods can", "conditions rods can take", "rods can take up to", "can take up to one", "take up to one hour", "up to one hour to", "to one hour to regain", "one hour to regain their", "hour to regain their sensitivity", "to regain their sensitivity whereas", "regain their sensitivity whereas cones", "their sensitivity whereas cones can", "sensitivity whereas cones can recover", "whereas cones can recover in", "cones can recover in a", "can recover in a few", "recover in a few minutes", "a few minutes a", "few minutes a process", "minutes a process called", "a process called dark adaptation", "process called dark adaptation and", "called dark adaptation and which", "dark adaptation and which allows", "adaptation and which allows us", "and which allows us to", "which allows us to retain", "allows us to retain visual", "us to retain visual perception", "to retain visual perception in", "retain visual perception in changing", "visual perception in 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cone cells", "changing light conditions.

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cone cells express three", "conditions.

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n", "and c", "c procollagen", "procollagen propeptides", "fibrillar collagen", "collagen molecules", "molecules aggregate", "aggregate into", "into microfibrillar", "microfibrillar arrays", "stabilized by", "by covalent", "covalent intermolecular", "intermolecular cross", "cross links.", "links. these", "these depend", "depend on", "on the", "the oxidative", "oxidative deamination", "deamination of", "of specific", "specific lysine", "lysine or", "or hydroxylysine", "hydroxylysine residues", "residues in", "in the", "the telopeptide", "telopeptide region", "region by", "by lysyl", "lysyl oxidase", "with the", "the subsequent", "subsequent spontaneous", "spontaneous formation", "formation of", "of covalent", "cross links", "pinnell &", "& martin", "martin 1968", "siegel et", "et al.", "al. 1970", "maki 2009", "nishioka et", "al. 2012", "2012 .", ". hydroxylysine", "hydroxylysine is", "is formed", "formed intracellularly", "intracellularly by", "by lysine", "lysine hydroxylases", "lh .", ". there", "there are", "are different", "different forms", "forms of", "of lh", "lh responsible", "responsible for", "for hydroxylation", "hydroxylation of", "of helical", "helical and", "and telopeptide", "telopeptide lysines", "royce &", "& barnes", "barnes 1985", "knott et", "et al.1997", "takaluoma et", "al. 2007", "myllyla 2007", "2007 .", ". the", "the chemistry", "chemistry of", "the cross", "links formed", "formed depends", "depends on", "on whether", "whether lysines", "lysines or", "or hydroxylysines", "hydroxylysines are", "are present", "present in", "the telopeptides", "barnes et", "al. 1974", "which depends", "the proportion", "proportion of", "collagen lysines", "lysines post", "post translationally", "translationally converted", "converted to", "to hydroxylysine", "hydroxylysine by", "by lh.", "lh. the", "the lysine", "lysine pathway", "pathway predominates", "predominates in", "in adult", "adult skin", "cornea and", "and sclera", "sclera while", "while the", "the hydroxylysine", "hydroxylysine pathway", "pathway occurs", "occurs primarily", "primarily in", "in bone", "embryonic skin", "skin and", "and most", "most connective", "connective tissues", "eyre 1987", "eyre &", "& wu", "wu 2005", "eyre et", "al. 2008", "2008 .", ". oxidative", "of lysine", "residues by", "by lox", "lox generates", "generates the", "the allysine", "allysine and", "and hydroxyallysine", "hydroxyallysine aldehydes", "aldehydes respectively.", "respectively. these", "these can", "can spontaneously", "spontaneously react", "react with", "with either", "either another", "another aldehyde", "aldehyde to", "to form", "form an", "an aldol", "aldol condensation", "condensation product", "intramolecular cross", "cross link", "or with", "with an", "an unmodified", "unmodified lysine", "hydroxylysine residue", "residue to", "form intermolecular", "cross links.

the", "links.

the pathway", "pathway of", "of cross", "cross linking", "linking is", "is regulated", "regulated primarily", "primarily by", "by the", "the hydroxylation", "hydroxylation pattern", "pattern of", "of telopeptide", "telopeptide and", "and triple", "triple helix", "helix domain", "domain lysine", "lysine residues.", "residues. when", "when lysine", "lysine residues", "residues are", "are the", "the source", "source of", "of aldehydes", "aldehydes formed", "formed by", "oxidase the", "allysine cross", "linking pathway", "pathway leads", "leads to", "to the", "the formation", "of aldimine", "aldimine cross", "2005 .", ". these", "these are", "are stable", "stable at", "at physiological", "physiological conditions", "conditions but", "but readily", "readily cleaved", "cleaved at", "at acid", "acid ph", "ph or", "or elevated", "elevated temperature.", "temperature. when", "when hydroxylysine", "the hydroxyallysine", "hydroxyallysine cross", "of more", "more stable", "stable ketoimine", "ketoimine cross", "links.

telopeptide", "

telopeptide lysine", "residues can", "can be", "be converted", "converted by", "lox to", "to allysine", "which can", "can react", "with a", "a helical", "helical hydroxylysine", "residue forming", "forming the", "lysine aldehyde", "aldehyde aldimine", "link dehydro", "dehydro hydroxylysino", "hydroxylysino norleucine", "bailey &", "& peach", "peach 1968", ". if", "if the", "telopeptide residue", "residue is", "is hydroxylysine", "hydroxyallysine formed", "lox can", "hydroxylysine forming", "the schiff", "schiff base", "which spontaneously", "spontaneously undergoes", "undergoes an", "an amadori", "amadori rearrangement", "rearrangement resulting", "resulting in", "the ketoimine", "link hydroxylysino", "hydroxylysino 5", "5 ketonorleucine", "hlknl .", ". this", "this stable", "stable cross", "link is", "formed in", "in tissues", "tissues where", "where telopeptide", "telopeptide residues", "are predominanly", "predominanly hydroxylated", "such as", "as foetal", "foetal bone", "bone and", "and cartilage", "accounting for", "for the", "the relative", "relative insolubility", "insolubility of", "collagen from", "from these", "these tissues", "bailey et", "al. 1998", "1998 .", ". in", "telopeptide hydroxyallysines", "hydroxyallysines can", "the epsilon", "epsilon amino", "amino group", "group of", "of a", "helical lysine", "robins &", "& bailey", "bailey 1975", "1975 .", "the resulting", "resulting schiff", "base undergoes", "undergoes amadori", "rearrangement to", "form lysino", "lysino hydroxynorleucine", "lhnl .", ". an", "an alternative", "alternative mechanism", "mechanism of", "of maturation", "maturation of", "of ketoimine", "links has", "has been", "been reported", "reported in", "in cartilage", "cartilage leading", "leading to", "of arginoline", "al. 2010", "2010 .", ".

these", "

these divalent", "divalent crosslinks", "crosslinks greatly", "greatly diminish", "diminish as", "as connective", "tissues mature", "due to", "to further", "further spontaneous", "spontaneous reactions", "& shimokomaki", "shimokomaki 1971", "bailey 1973", "with neighbouring", "neighbouring peptides", "peptides that", "that result", "result in", "in tri", "and tetrafunctional", "tetrafunctional cross", "links. in", "in mature", "mature tissues", "tissues collagen", "collagen cross", "links are", "are predominantly", "predominantly trivalent.", "trivalent. the", "the most", "most common", "common are", "are pyridinoline", "pyridinoline or", "or 3", "3 hydroxypyridinium", "hydroxypyridinium cross", "namely hydroxylysyl", "hydroxylysyl pyridinoline", "hl pyr", "lysyl pyridinoline", "l pyr", "ogawa et", "al. 1982", "fujimoto et", "al. 1978", "1978 .", ". hl", "pyr is", "formed from", "from three", "three hydroxylysine", "hlknl plus", "plus a", "a further", "further hydroxyallysine.", "hydroxyallysine. it", "it predominates", "in highly", "highly hydroxylated", "hydroxylated collagens", "collagens such", "as type", "type ii", "ii collagen", "collagen in", "in cartilage.", "cartilage. l", "from two", "two hydroxylysines", "hydroxylysines and", "and a", "a lysine", "lknl plus", "further hydroxyallysine", "found mostly", "mostly in", "in calcified", "calcified tissues", ". trivalent", "trivalent collagen", "links can", "can also", "also form", "form as", "as pyrroles", "either lysyl", "lysyl pyrrole", "l pyrrole", "or hydroxylysyl", "hydroxylysyl pyrrole", "hl pyrrole", "respectively formed", "formed when", "when lknl", "lknl or", "or hlknl", "hlknl react", "with allysine", "scott et", "al. 1981", "kuypers et", "al. 1992", "1992 .", ". a", "further three", "three way", "way crosslink", "crosslink can", "can form", "form when", "when deh", "deh hlnl", "hlnl reacts", "reacts with", "with histidine", "histidine to", "form histidino", "histidino hydroxylysinonorleucine", "found in", "in skin", "and cornea", "yamauchi et", "al. 1987", "1996 .", "this can", "an additional", "additional lysine", "lysine to", "form the", "the tetrafunctional", "link histidinohydroxymerodesmosine", "reiser et", "al. 1996", ".
", "

another", "
another mechanism", "mechanism which", "which could", "could be", "be involved", "involved in", "linking of", "collagen iv", "iv networks", "networks is", "is the", "the sulfilimine", "sulfilimine bond", "vanacore et", "al. 2009", "catalyzed by", "by peroxidasin", "an enzyme", "enzyme found", "in basement", "basement membrane", "bhave 2012", "2012 .

to", ".

to improve", "improve clarity", "clarity inter", "inter chain", "chain cross", "is represented", "represented here", "here for", "for collagen", "collagen type", "type i", "i only.", "only. although", "although the", "of each", "each type", "type of", "here as", "as an", "an independent", "independent event", "the partial", "partial and", "and random", "random nature", "nature of", "lysine hydroxylation", "hydroxylation and", "and subsequent", "subsequent lysyl", "lysyl oxidation", "oxidation means", "means that", "that any", "any combination", "combination of", "of these", "these cross", "linking events", "events could", "could occur", "occur within", "within the", "the same", "same collagen", "collagen fibril", "fibril .", "after removal of", "removal of the", "of the n", "n and", "and c procollagen", "c procollagen propeptides", "propeptides fibrillar", "fibrillar collagen molecules", "collagen molecules aggregate", "molecules aggregate into", "aggregate into microfibrillar", "into microfibrillar arrays", "arrays stabilized", "stabilized by covalent", "by covalent intermolecular", "covalent intermolecular cross", "intermolecular cross links.", "cross links. these", "links. these depend", "these depend on", "depend on the", "on the oxidative", "the oxidative deamination", "oxidative deamination of", "deamination of specific", "of specific lysine", "specific lysine or", "lysine or hydroxylysine", "or hydroxylysine residues", "hydroxylysine residues in", "residues in the", "in the telopeptide", "the telopeptide region", "telopeptide region by", "region by lysyl", "by lysyl oxidase", "oxidase lox", "lox with", "with the subsequent", "the subsequent spontaneous", "subsequent spontaneous formation", "spontaneous formation of", "formation of covalent", "of covalent intermolecular", "intermolecular cross links", "links pinnell", "pinnell & martin", "& martin 1968", "1968 siegel", "siegel et al.", "et al. 1970", "1970 1974", "1974 maki", "2009 nishioka", "nishioka et al.", "et al. 2012", "al. 2012 .", "2012 . hydroxylysine", ". hydroxylysine is", "hydroxylysine is formed", "is formed intracellularly", "formed intracellularly by", "intracellularly by lysine", "by lysine hydroxylases", "hydroxylases lh", "lh . there", ". there are", "there are different", "are different forms", "different forms of", "forms of lh", "of lh responsible", "lh responsible for", "responsible for hydroxylation", "for hydroxylation of", "hydroxylation of helical", "of helical and", "helical and telopeptide", "and telopeptide lysines", "lysines royce", "royce & barnes", "& barnes 1985", "1985 knott", "knott et al.1997", "al.1997 takaluoma", "takaluoma et al.", "et al. 2007", "2007 myllyla", "myllyla 2007 .", "2007 . the", ". the chemistry", "the chemistry of", "chemistry of the", "of the cross", "the cross links", "cross links formed", "links formed depends", "formed depends on", "depends on whether", "on whether lysines", "whether lysines or", "lysines or hydroxylysines", "or hydroxylysines are", "hydroxylysines are present", "are present in", "present in the", "in the telopeptides", "telopeptides barnes", "barnes et al.", "et al. 1974", "which depends on", "depends on the", "on the proportion", "the proportion of", "proportion of collagen", "of collagen lysines", "collagen lysines post", "lysines post translationally", "post translationally converted", "translationally converted to", "converted to hydroxylysine", "to hydroxylysine by", "hydroxylysine by lh.", "by lh. the", "lh. the lysine", "the lysine pathway", "lysine pathway predominates", "pathway predominates in", "predominates in adult", "in adult skin", "skin cornea", "cornea and sclera", "and sclera while", "sclera while the", "while the hydroxylysine", "the hydroxylysine pathway", "hydroxylysine pathway occurs", "pathway occurs primarily", "occurs primarily in", "primarily in bone", "bone cartilage", "cartilage ligament", "ligament tendons", "tendons embryonic", "embryonic skin and", "skin and most", "and most connective", "most connective tissues", "tissues eyre", "1987 eyre", "eyre & wu", "& wu 2005", "2005 eyre", "eyre et al.", "et al. 2008", "al. 2008 .", "2008 . oxidative", ". oxidative deamination", "deamination of lysine", "of lysine or", "hydroxylysine residues by", "residues by lox", "by lox generates", "lox generates the", "generates the allysine", "the allysine and", "allysine and hydroxyallysine", "and hydroxyallysine aldehydes", "hydroxyallysine aldehydes respectively.", "aldehydes respectively. these", "respectively. these can", "these can spontaneously", "can spontaneously react", "spontaneously react with", "react with either", "with either another", "either another aldehyde", "another aldehyde to", "aldehyde to form", "to form an", "form an aldol", "an aldol condensation", "aldol condensation product", "product intramolecular", "intramolecular cross link", "or with an", "with an unmodified", "an unmodified lysine", "unmodified lysine or", "or hydroxylysine residue", "hydroxylysine residue to", "residue to form", "to form intermolecular", "form intermolecular cross", "intermolecular cross links.

the", "cross links.

the pathway", "links.

the pathway of", "pathway of cross", "of cross linking", "cross linking is", "linking is regulated", "is regulated primarily", "regulated primarily by", "primarily by the", "by the hydroxylation", "the hydroxylation pattern", "hydroxylation pattern of", "pattern of telopeptide", "of telopeptide and", "telopeptide and triple", "and triple helix", "triple helix domain", "helix domain lysine", "domain lysine residues.", "lysine residues. when", "residues. when lysine", "when lysine residues", "lysine residues are", "residues are the", "are the source", "the source of", "source of aldehydes", "of aldehydes formed", "aldehydes formed by", "formed by lysyl", "lysyl oxidase the", "oxidase the allysine", "the allysine cross", "allysine cross linking", "cross linking pathway", "linking pathway leads", "pathway leads to", "leads to the", "to the formation", "the formation of", "formation of aldimine", "of aldimine cross", "aldimine cross links", "links eyre", "wu 2005 .", "2005 . these", ". these are", "these are stable", "are stable at", "stable at physiological", "at physiological conditions", "physiological conditions but", "conditions but readily", "but readily cleaved", "readily cleaved at", "cleaved at acid", "at acid ph", "acid ph or", "ph or elevated", "or elevated temperature.", "elevated temperature. when", "temperature. when hydroxylysine", "when hydroxylysine residues", "hydroxylysine residues are", "oxidase the hydroxyallysine", "the hydroxyallysine cross", "hydroxyallysine cross linking", "formation of more", "of more stable", "more stable ketoimine", "stable ketoimine cross", "ketoimine cross links.", "cross links.

telopeptide", "links.

telopeptide lysine", "

telopeptide lysine residues", "lysine residues can", "residues can be", "can be converted", "be converted by", "converted by lox", "by lox to", "lox to allysine", "allysine which", "which can react", "can react with", "react with a", "with a helical", "a helical hydroxylysine", "helical hydroxylysine residue", "hydroxylysine residue forming", "residue forming the", "forming the lysine", "the lysine aldehyde", "lysine aldehyde aldimine", "aldehyde aldimine cross", "aldimine cross link", "cross link dehydro", "link dehydro hydroxylysino", "dehydro hydroxylysino norleucine", "norleucine dehhlnl", "bailey & peach", "& peach 1968", "1968 eyre", "2008 . if", ". if the", "if the telopeptide", "the telopeptide residue", "telopeptide residue is", "residue is hydroxylysine", "hydroxylysine the", "the hydroxyallysine formed", "hydroxyallysine formed by", "formed by lox", "by lox can", "lox can react", "helical hydroxylysine forming", "hydroxylysine forming the", "forming the schiff", "the schiff base", "base which", "which spontaneously undergoes", "spontaneously undergoes an", "undergoes an amadori", "an amadori rearrangement", "amadori rearrangement resulting", "rearrangement resulting in", "resulting in the", "in the ketoimine", "the ketoimine cross", "ketoimine cross link", "cross link hydroxylysino", "link hydroxylysino 5", "hydroxylysino 5 ketonorleucine", "ketonorleucine hlknl", "hlknl . this", ". this stable", "this stable cross", "stable cross link", "cross link is", "link is formed", "is formed in", "formed in tissues", "in tissues where", "tissues where telopeptide", "where telopeptide residues", "telopeptide residues are", "residues are predominanly", "are predominanly hydroxylated", "hydroxylated such", "such as foetal", "as foetal bone", "foetal bone and", "bone and cartilage", "cartilage accounting", "accounting for the", "for the relative", "the relative insolubility", "relative insolubility of", "insolubility of collagen", "of collagen from", "collagen from these", "from these tissues", "tissues bailey", "bailey et al.", "et al. 1998", "al. 1998 .", "1998 . in", ". in bone", "bone telopeptide", "telopeptide hydroxyallysines can", "hydroxyallysines can react", "react with the", "with the epsilon", "the epsilon amino", "epsilon amino group", "amino group of", "group of a", "of a helical", "a helical lysine", "lysine robins", "robins & bailey", "& bailey 1975", "bailey 1975 .", "1975 . the", ". the resulting", "the resulting schiff", "resulting schiff base", "schiff base undergoes", "base undergoes amadori", "undergoes amadori rearrangement", "amadori rearrangement to", "rearrangement to form", "to form lysino", "form lysino hydroxynorleucine", "hydroxynorleucine lhnl", "lhnl . an", ". an alternative", "an alternative mechanism", "alternative mechanism of", "mechanism of maturation", "of maturation of", "maturation of ketoimine", "of ketoimine cross", "ketoimine cross links", "cross links has", "links has been", "has been reported", "been reported in", "reported in cartilage", "in cartilage leading", "cartilage leading to", "leading to the", "formation of arginoline", "arginoline eyre", "et al. 2010", "al. 2010 .", "2010 .

these", ".

these divalent", "

these divalent crosslinks", "divalent crosslinks greatly", "crosslinks greatly diminish", "greatly diminish as", "diminish as connective", "as connective tissues", "connective tissues mature", "mature due", "due to further", "to further spontaneous", "further spontaneous reactions", "reactions bailey", "bailey & shimokomaki", "& shimokomaki 1971", "1971 robins", "& bailey 1973", "1973 with", "with neighbouring peptides", "neighbouring peptides that", "peptides that result", "that result in", "result in tri", "tri and", "and tetrafunctional cross", "tetrafunctional cross links.", "cross links. in", "links. in mature", "in mature tissues", "mature tissues collagen", "tissues collagen cross", "collagen cross links", "cross links are", "links are predominantly", "are predominantly trivalent.", "predominantly trivalent. the", "trivalent. the most", "the most common", "most common are", "common are pyridinoline", "are pyridinoline or", "pyridinoline or 3", "or 3 hydroxypyridinium", "3 hydroxypyridinium cross", "hydroxypyridinium cross links", "links namely", "namely hydroxylysyl pyridinoline", "pyridinoline hl", "pyr and", "and lysyl", "pyridinoline l", "pyr cross", "1987 ogawa", "ogawa et al.", "et al. 1982", "1982 fujimoto", "fujimoto et al.", "et al. 1978", "al. 1978 .", "1978 . hl", ". hl pyr", "hl pyr is", "pyr is formed", "is formed from", "formed from three", "from three hydroxylysine", "three hydroxylysine residues", "residues hlknl", "hlknl plus a", "plus a further", "a further hydroxyallysine.", "further hydroxyallysine. it", "hydroxyallysine. it predominates", "it predominates in", "predominates in highly", "in highly hydroxylated", "highly hydroxylated collagens", "hydroxylated collagens such", "collagens such as", "such as type", "as type ii", "type ii collagen", "ii collagen in", "collagen in cartilage.", "in cartilage. l", "cartilage. l pyr", "l pyr is", "formed from two", "from two hydroxylysines", "two hydroxylysines and", "hydroxylysines and a", "and a lysine", "lysine lknl", "lknl plus a", "a further hydroxyallysine", "hydroxyallysine found", "found mostly in", "mostly in calcified", "in calcified tissues", "1998 . trivalent", ". trivalent collagen", "trivalent collagen cross", "cross links can", "links can also", "can also form", "also form as", "form as pyrroles", "pyrroles either", "either lysyl pyrrole", "pyrrole l", "pyrrole or", "or hydroxylysyl pyrrole", "pyrrole hl", "respectively formed when", "formed when lknl", "when lknl or", "lknl or hlknl", "or hlknl react", "hlknl react with", "react with allysine", "allysine scott", "scott et al.", "et al. 1981", "1981 kuypers", "kuypers et al.", "et al. 1992", "al. 1992 .", "1992 . a", ". a further", "a further three", "further three way", "three way crosslink", "way crosslink can", "crosslink can form", "can form when", "form when deh", "when deh hlnl", "deh hlnl reacts", "hlnl reacts with", "reacts with histidine", "with histidine to", "histidine to form", "to form histidino", "form histidino hydroxylysinonorleucine", "hydroxylysinonorleucine hhl", "found in skin", "in skin and", "skin and cornea", "cornea yamauchi", "yamauchi et al.", "et al. 1987", "1987 1996", "1996 . this", ". this can", "this can react", "react with an", "with an additional", "an additional lysine", "additional lysine to", "lysine to form", "to form the", "form the tetrafunctional", "the tetrafunctional cross", "tetrafunctional cross link", "cross link histidinohydroxymerodesmosine", "histidinohydroxymerodesmosine reiser", "reiser et al.", "1992 yamauchi", "et al. 1996", "al. 1996 .", "1996 .
", ".

another", "

another mechanism", "
another mechanism which", "mechanism which could", "which could be", "could be involved", "be involved in", "involved in the", "in the cross", "the cross linking", "cross linking of", "linking of collagen", "of collagen iv", "collagen iv networks", "iv networks is", "networks is the", "is the sulfilimine", "the sulfilimine bond", "bond vanacore", "vanacore et al.", "et al. 2009", "catalyzed by peroxidasin", "peroxidasin an", "an enzyme found", "enzyme found in", "found in basement", "in basement membrane", "membrane bhave", "bhave 2012 .

to", "2012 .

to improve", ".

to improve clarity", "improve clarity inter", "clarity inter chain", "inter chain cross", "chain cross linking", "linking is represented", "is represented here", "represented here for", "here for collagen", "for collagen type", "collagen type i", "type i only.", "i only. although", "only. although the", "although the formation", "formation of each", "of each type", "each type of", "type of cross", "of cross link", "link is represented", "represented here as", "here as an", "as an independent", "an independent event", "event the", "the partial and", "partial and random", "and random nature", "random nature of", "nature of lysine", "of lysine hydroxylation", "lysine hydroxylation and", "hydroxylation and subsequent", "and subsequent lysyl", "subsequent lysyl oxidation", "lysyl oxidation means", "oxidation means that", "means that any", "that any combination", "any combination of", "combination of these", "of these cross", "these cross linking", "cross linking events", "linking events could", "events could occur", "could occur within", "occur within the", "within the same", "the same collagen", "same collagen fibril", "collagen fibril .", "after removal of the", "removal of the n", "the n and", "n and c", "and c procollagen propeptides", "procollagen propeptides fibrillar", "propeptides fibrillar collagen", "fibrillar collagen molecules aggregate", "collagen molecules aggregate into", "molecules aggregate into microfibrillar", "aggregate into microfibrillar arrays", "microfibrillar arrays stabilized", "arrays stabilized by", "stabilized by covalent intermolecular", "by covalent intermolecular cross", "covalent intermolecular cross links.", "intermolecular cross links. these", "cross links. these depend", "links. these depend on", "these depend on the", "depend on the oxidative", "on the oxidative deamination", "the oxidative deamination of", "oxidative deamination of specific", "deamination of specific lysine", "of specific lysine or", "specific lysine or hydroxylysine", "lysine or hydroxylysine residues", "or hydroxylysine residues in", "hydroxylysine residues in the", "residues in the telopeptide", "in the telopeptide region", "the telopeptide region by", "telopeptide region by lysyl", "region by lysyl oxidase", "lysyl oxidase lox", "lox with the", "with the subsequent spontaneous", "the subsequent spontaneous formation", "subsequent spontaneous formation of", "spontaneous formation of covalent", "formation of covalent intermolecular", "of covalent intermolecular cross", "covalent intermolecular cross links", "cross links pinnell", "links pinnell &", "pinnell & martin 1968", "martin 1968 siegel", "1968 siegel et", "siegel et al. 1970", "al. 1970 1974", "1974 maki 2009", "maki 2009 nishioka", "2009 nishioka et", "nishioka et al. 2012", "et al. 2012 .", "al. 2012 . hydroxylysine", "2012 . hydroxylysine is", ". hydroxylysine is formed", "hydroxylysine is formed intracellularly", "is formed intracellularly by", "formed intracellularly by lysine", "intracellularly by lysine hydroxylases", "lysine hydroxylases lh", "hydroxylases lh .", "lh . there are", ". there are different", "there are different forms", "are different forms of", "different forms of lh", "forms of lh responsible", "of lh responsible for", "lh responsible for hydroxylation", "responsible for hydroxylation of", "for hydroxylation of helical", "hydroxylation of helical and", "of helical and telopeptide", "helical and telopeptide lysines", "telopeptide lysines royce", "lysines royce &", "royce & barnes 1985", "barnes 1985 knott", "1985 knott et", "et al.1997 takaluoma", "al.1997 takaluoma et", "takaluoma et al. 2007", "al. 2007 myllyla", "2007 myllyla 2007", "myllyla 2007 . the", "2007 . the chemistry", ". the chemistry of", "the chemistry of the", "chemistry of the cross", "of the cross links", "the cross links formed", "cross links formed depends", "links formed depends on", "formed depends on whether", "depends on whether lysines", "on whether lysines or", "whether lysines or hydroxylysines", "lysines or hydroxylysines are", "or hydroxylysines are present", "hydroxylysines are present in", "are present in the", "present in the telopeptides", "the telopeptides barnes", "telopeptides barnes et", "barnes et al. 1974", "1974 which", "which depends on the", "depends on the proportion", "on the proportion of", "the proportion of collagen", "proportion of collagen lysines", "of collagen lysines post", "collagen lysines post translationally", "lysines post translationally converted", "post translationally converted to", "translationally converted to hydroxylysine", "converted to hydroxylysine by", "to hydroxylysine by lh.", "hydroxylysine by lh. the", "by lh. the lysine", "lh. the lysine pathway", "the lysine pathway predominates", "lysine pathway predominates in", "pathway predominates in adult", "predominates in adult skin", "adult skin cornea", "skin cornea and", "cornea and sclera while", "and sclera while the", "sclera while the hydroxylysine", "while the hydroxylysine pathway", "the hydroxylysine pathway occurs", "hydroxylysine pathway occurs primarily", "pathway occurs primarily in", "occurs primarily in bone", "in bone cartilage", "tendons embryonic skin", "embryonic skin and most", "skin and most connective", "and most connective tissues", "connective tissues eyre", "tissues eyre 1987", "eyre 1987 eyre", "1987 eyre &", "eyre & wu 2005", "wu 2005 eyre", "2005 eyre et", "eyre et al. 2008", "et al. 2008 .", "al. 2008 . oxidative", "2008 . oxidative deamination", ". oxidative deamination of", "oxidative deamination of lysine", "deamination of lysine or", "of lysine or hydroxylysine", "or hydroxylysine residues by", "hydroxylysine residues by lox", "residues by lox generates", "by lox generates the", "lox generates the allysine", "generates the allysine and", "the allysine and hydroxyallysine", "allysine and hydroxyallysine aldehydes", "and hydroxyallysine aldehydes respectively.", "hydroxyallysine aldehydes respectively. these", "aldehydes respectively. these can", "respectively. these can spontaneously", "these can spontaneously react", "can spontaneously react with", "spontaneously react with either", "react with either another", "with either another aldehyde", "either another aldehyde to", "another aldehyde to form", "aldehyde to form an", "to form an aldol", "form an aldol condensation", "an aldol condensation product", "condensation product intramolecular", "product intramolecular cross", "link or", "or with an unmodified", "with an unmodified lysine", "an unmodified lysine or", "unmodified lysine or hydroxylysine", "lysine or hydroxylysine residue", "or hydroxylysine residue to", "hydroxylysine residue to form", "residue to form intermolecular", "to form intermolecular cross", "form intermolecular cross links.

the", "intermolecular cross links.

the pathway", "cross links.

the pathway of", "links.

the pathway of cross", "pathway of cross linking", "of cross linking is", "cross linking is regulated", "linking is regulated primarily", "is regulated primarily by", "regulated primarily by the", "primarily by the hydroxylation", "by the hydroxylation pattern", "the hydroxylation pattern of", "hydroxylation pattern of telopeptide", "pattern of telopeptide and", "of telopeptide and triple", "telopeptide and triple helix", "and triple helix domain", "triple helix domain lysine", "helix domain lysine residues.", "domain lysine residues. when", "lysine residues. when lysine", "residues. when lysine residues", "when lysine residues are", "lysine residues are the", "residues are the source", "are the source of", "the source of aldehydes", "source of aldehydes formed", "of aldehydes formed by", "aldehydes formed by lysyl", "formed by lysyl oxidase", "by lysyl oxidase the", "lysyl oxidase the allysine", "oxidase the allysine cross", "the allysine cross linking", "allysine cross linking pathway", "cross linking pathway leads", "linking pathway leads to", "pathway leads to the", "leads to the formation", "to the formation of", "the formation of aldimine", "formation of aldimine cross", "of aldimine cross links", "cross links eyre", "links eyre &", "& wu 2005 .", "wu 2005 . these", "2005 . these are", ". these are stable", "these are stable at", "are stable at physiological", "stable at physiological conditions", "at physiological conditions but", "physiological conditions but readily", "conditions but readily cleaved", "but readily cleaved at", "readily cleaved at acid", "cleaved at acid ph", "at acid ph or", "acid ph or elevated", "ph or elevated temperature.", "or elevated temperature. when", "elevated temperature. when hydroxylysine", "temperature. when hydroxylysine residues", "when hydroxylysine residues are", "hydroxylysine residues are the", "lysyl oxidase the hydroxyallysine", "oxidase the hydroxyallysine cross", "the hydroxyallysine cross linking", "hydroxyallysine cross linking pathway", "the formation of more", "formation of more stable", "of more stable ketoimine", "more stable ketoimine cross", "stable ketoimine cross links.", "ketoimine cross links.

telopeptide", "cross links.

telopeptide lysine", "links.

telopeptide lysine residues", "

telopeptide lysine residues can", "lysine residues can be", "residues can be converted", "can be converted by", "be converted by lox", "converted by lox to", "by lox to allysine", "to allysine which", "allysine which can", "which can react with", "can react with a", "react with a helical", "with a helical hydroxylysine", "a helical hydroxylysine residue", "helical hydroxylysine residue forming", "hydroxylysine residue forming the", "residue forming the lysine", "forming the lysine aldehyde", "the lysine aldehyde aldimine", "lysine aldehyde aldimine cross", "aldehyde aldimine cross link", "aldimine cross link dehydro", "cross link dehydro hydroxylysino", "link dehydro hydroxylysino norleucine", "hydroxylysino norleucine dehhlnl", "dehhlnl bailey", "bailey & peach 1968", "peach 1968 eyre", "1968 eyre et", "al. 2008 . if", "2008 . if the", ". if the telopeptide", "if the telopeptide residue", "the telopeptide residue is", "telopeptide residue is hydroxylysine", "is hydroxylysine the", "hydroxylysine the hydroxyallysine", "the hydroxyallysine formed by", "hydroxyallysine formed by lox", "formed by lox can", "by lox can react", "lox can react with", "a helical hydroxylysine forming", "helical hydroxylysine forming the", "hydroxylysine forming the schiff", "forming the schiff base", "schiff base which", "base which spontaneously", "which spontaneously undergoes an", "spontaneously undergoes an amadori", "undergoes an amadori rearrangement", "an amadori rearrangement resulting", "amadori rearrangement resulting in", "rearrangement resulting in the", "resulting in the ketoimine", "in the ketoimine cross", "the ketoimine cross link", "ketoimine cross link hydroxylysino", "cross link hydroxylysino 5", "link hydroxylysino 5 ketonorleucine", "5 ketonorleucine hlknl", "ketonorleucine hlknl .", "hlknl . this stable", ". this stable cross", "this stable cross link", "stable cross link is", "cross link is formed", "link is formed in", "is formed in tissues", "formed in tissues where", "in tissues where telopeptide", "tissues where telopeptide residues", "where telopeptide residues are", "telopeptide residues are predominanly", "residues are predominanly hydroxylated", "predominanly hydroxylated such", "hydroxylated such as", "such as foetal bone", "as foetal bone and", "foetal bone and cartilage", "and cartilage accounting", "cartilage accounting for", "accounting for the relative", "for the relative insolubility", "the relative insolubility of", "relative insolubility of collagen", "insolubility of collagen from", "of collagen from these", "collagen from these tissues", "these tissues bailey", "tissues bailey et", "bailey et al. 1998", "et al. 1998 .", "al. 1998 . in", "1998 . in bone", "in bone telopeptide", "bone telopeptide hydroxyallysines", "telopeptide hydroxyallysines can react", "hydroxyallysines can react with", "can react with the", "react with the epsilon", "with the epsilon amino", "the epsilon amino group", "epsilon amino group of", "amino group of a", "group of a helical", "of a helical lysine", "helical lysine robins", "lysine robins &", "robins & bailey 1975", "& bailey 1975 .", "bailey 1975 . the", "1975 . the resulting", ". the resulting schiff", "the resulting schiff base", "resulting schiff base undergoes", "schiff base undergoes amadori", "base undergoes amadori rearrangement", "undergoes amadori rearrangement to", "amadori rearrangement to form", "rearrangement to form lysino", "to form lysino hydroxynorleucine", "lysino hydroxynorleucine lhnl", "hydroxynorleucine lhnl .", "lhnl . an alternative", ". an alternative mechanism", "an alternative mechanism of", "alternative mechanism of maturation", "mechanism of maturation of", "of maturation of ketoimine", "maturation of ketoimine cross", "of ketoimine cross links", "ketoimine cross links has", "cross links has been", "links has been reported", "has been reported in", "been reported in cartilage", "reported in cartilage leading", "in cartilage leading to", "cartilage leading to the", "leading to the formation", "the formation of arginoline", "of arginoline eyre", "arginoline eyre et", "eyre et al. 2010", "et al. 2010 .", "al. 2010 .

these", "2010 .

these divalent", ".

these divalent crosslinks", "

these divalent crosslinks greatly", "divalent crosslinks greatly diminish", "crosslinks greatly diminish as", "greatly diminish as connective", "diminish as connective tissues", "as connective tissues mature", "tissues mature due", "mature due to", "due to further spontaneous", "to further spontaneous reactions", "spontaneous reactions bailey", "reactions bailey &", "bailey & shimokomaki 1971", "shimokomaki 1971 robins", "1971 robins &", "robins & bailey 1973", "bailey 1973 with", "1973 with neighbouring", "with neighbouring peptides that", "neighbouring peptides that result", "peptides that result in", "that result in tri", "in tri and", "tri and tetrafunctional", "and tetrafunctional cross links.", "tetrafunctional cross links. in", "cross links. in mature", "links. in mature tissues", "in mature tissues collagen", "mature tissues collagen cross", "tissues collagen cross links", "collagen cross links are", "cross links are predominantly", "links are predominantly trivalent.", "are predominantly trivalent. the", "predominantly trivalent. the most", "trivalent. the most common", "the most common are", "most common are pyridinoline", "common are pyridinoline or", "are pyridinoline or 3", "pyridinoline or 3 hydroxypyridinium", "or 3 hydroxypyridinium cross", "3 hydroxypyridinium cross links", "cross links namely", "links namely hydroxylysyl", "hydroxylysyl pyridinoline hl", "pyridinoline hl pyr", "hl pyr and", "and lysyl pyridinoline", "lysyl pyridinoline l", "pyridinoline l pyr", "l pyr cross", "pyr cross links", "links eyre 1987", "eyre 1987 ogawa", "1987 ogawa et", "ogawa et al. 1982", "al. 1982 fujimoto", "1982 fujimoto et", "fujimoto et al. 1978", "et al. 1978 .", "al. 1978 . hl", "1978 . hl pyr", ". hl pyr is", "hl pyr is formed", "pyr is formed from", "is formed from three", "formed from three hydroxylysine", "from three hydroxylysine residues", "hydroxylysine residues hlknl", "residues hlknl plus", "hlknl plus a further", "plus a further hydroxyallysine.", "a further hydroxyallysine. it", "further hydroxyallysine. it predominates", "hydroxyallysine. it predominates in", "it predominates in highly", "predominates in highly hydroxylated", "in highly hydroxylated collagens", "highly hydroxylated collagens such", "hydroxylated collagens such as", "collagens such as type", "such as type ii", "as type ii collagen", "type ii collagen in", "ii collagen in cartilage.", "collagen in cartilage. l", "in cartilage. l pyr", "cartilage. l pyr is", "l pyr is formed", "is formed from two", "formed from two hydroxylysines", "from two hydroxylysines and", "two hydroxylysines and a", "hydroxylysines and a lysine", "a lysine lknl", "lysine lknl plus", "lknl plus a further", "plus a further hydroxyallysine", "further hydroxyallysine found", "hydroxyallysine found mostly", "found mostly in calcified", "mostly in calcified tissues", "calcified tissues bailey", "al. 1998 . trivalent", "1998 . trivalent collagen", ". trivalent collagen cross", "trivalent collagen cross links", "collagen cross links can", "cross links can also", "links can also form", "can also form as", "also form as pyrroles", "as pyrroles either", "pyrroles either lysyl", "lysyl pyrrole l", "pyrrole l pyrrole", "l pyrrole or", "pyrrole or hydroxylysyl", "hydroxylysyl pyrrole hl", "pyrrole hl pyrrole", "pyrrole respectively", "respectively formed when lknl", "formed when lknl or", "when lknl or hlknl", "lknl or hlknl react", "or hlknl react with", "hlknl react with allysine", "with allysine scott", "allysine scott et", "scott et al. 1981", "al. 1981 kuypers", "1981 kuypers et", "kuypers et al. 1992", "et al. 1992 .", "al. 1992 . a", "1992 . a further", ". a further three", "a further three way", "further three way crosslink", "three way crosslink can", "way crosslink can form", "crosslink can form when", "can form when deh", "form when deh hlnl", "when deh hlnl reacts", "deh hlnl reacts with", "hlnl reacts with histidine", "reacts with histidine to", "with histidine to form", "histidine to form histidino", "to form histidino hydroxylysinonorleucine", "histidino hydroxylysinonorleucine hhl", "hhl found", "found in skin and", "in skin and cornea", "and cornea yamauchi", "cornea yamauchi et", "yamauchi et al. 1987", "al. 1987 1996", "1987 1996 .", "1996 . this can", ". this can react", "this can react with", "can react with an", "react with an additional", "with an additional lysine", "an additional lysine to", "additional lysine to form", "lysine to form the", "to form the tetrafunctional", "form the tetrafunctional cross", "the tetrafunctional cross link", "tetrafunctional cross link histidinohydroxymerodesmosine", "link histidinohydroxymerodesmosine reiser", "histidinohydroxymerodesmosine reiser et", "reiser et al. 1992", "al. 1992 yamauchi", "1992 yamauchi et", "yamauchi et al. 1996", "et al. 1996 .", "al. 1996 .
", "1996 .

another", ".

another mechanism", "

another mechanism which", "
another mechanism which could", "mechanism which could be", "which could be involved", "could be involved in", "be involved in the", "involved in the cross", "in the cross linking", "the cross linking of", "cross linking of collagen", "linking of collagen iv", "of collagen iv networks", "collagen iv networks is", "iv networks is the", "networks is the sulfilimine", "is the sulfilimine bond", "sulfilimine bond vanacore", "bond vanacore et", "vanacore et al. 2009", "2009 catalyzed", "by peroxidasin an", "peroxidasin an enzyme", "an enzyme found in", "enzyme found in basement", "found in basement membrane", "basement membrane bhave", "membrane bhave 2012", "bhave 2012 .

to improve", "2012 .

to improve clarity", ".

to improve clarity inter", "improve clarity inter chain", "clarity inter chain cross", "inter chain cross linking", "chain cross linking is", "cross linking is represented", "linking is represented here", "is represented here for", "represented here for collagen", "here for collagen type", "for collagen type i", "collagen type i only.", "type i only. although", "i only. although the", "only. although the formation", "although the formation of", "the formation of each", "formation of each type", "of each type of", "each type of cross", "type of cross link", "of cross link is", "cross link is represented", "link is represented here", "is represented here as", "represented here as an", "here as an independent", "as an independent event", "independent event the", "event the partial", "the partial and random", "partial and random nature", "and random nature of", "random nature of lysine", "nature of lysine hydroxylation", "of lysine hydroxylation and", "lysine hydroxylation and subsequent", "hydroxylation and subsequent lysyl", "and subsequent lysyl oxidation", "subsequent lysyl oxidation means", "lysyl oxidation means that", "oxidation means that any", "means that any combination", "that any combination of", "any combination of these", "combination of these cross", "of these cross linking", "these cross linking events", "cross linking events could", "linking events could occur", "events could occur within", "could occur within the", "occur within the same", "within the same collagen", "the same collagen fibril", "same collagen fibril .", "after removal of the n", "of the n and", "the n and c", "n and c procollagen", "c procollagen propeptides fibrillar", "procollagen propeptides fibrillar collagen", "propeptides fibrillar collagen molecules", "fibrillar collagen molecules aggregate into", "collagen molecules aggregate into microfibrillar", "molecules aggregate into microfibrillar arrays", "into microfibrillar arrays stabilized", "microfibrillar arrays stabilized by", "arrays stabilized by covalent", "stabilized by covalent intermolecular cross", "by covalent intermolecular cross links.", "covalent intermolecular cross links. these", "intermolecular cross links. these depend", "cross links. these depend on", "links. these depend on the", "these depend on the oxidative", "depend on the oxidative deamination", "on the oxidative deamination of", "the oxidative deamination of specific", "oxidative deamination of specific lysine", "deamination of specific lysine or", "of specific lysine or hydroxylysine", "specific lysine or hydroxylysine residues", "lysine or hydroxylysine residues in", "or hydroxylysine residues in the", "hydroxylysine residues in the telopeptide", "residues in the telopeptide region", "in the telopeptide region by", "the telopeptide region by lysyl", "telopeptide region by lysyl oxidase", "by lysyl oxidase lox", "oxidase lox with", "lox with the subsequent", "with the subsequent spontaneous formation", "the subsequent spontaneous formation of", "subsequent spontaneous formation of covalent", "spontaneous formation of covalent intermolecular", "formation of covalent intermolecular cross", "of covalent intermolecular cross links", "intermolecular cross links pinnell", "cross links pinnell &", "links pinnell & martin", "& martin 1968 siegel", "martin 1968 siegel et", "1968 siegel et al.", "et al. 1970 1974", "1970 1974 maki", "maki 2009 nishioka et", "2009 nishioka et al.", "nishioka et al. 2012 .", "et al. 2012 . hydroxylysine", "al. 2012 . hydroxylysine is", "2012 . hydroxylysine is formed", ". hydroxylysine is formed intracellularly", "hydroxylysine is formed intracellularly by", "is formed intracellularly by lysine", "formed intracellularly by lysine hydroxylases", "by lysine hydroxylases lh", "lysine hydroxylases lh .", "hydroxylases lh . there", "lh . there are different", ". there are different forms", "there are different forms of", "are different forms of lh", "different forms of lh responsible", "forms of lh responsible for", "of lh responsible for hydroxylation", "lh responsible for hydroxylation of", "responsible for hydroxylation of helical", "for hydroxylation of helical and", "hydroxylation of helical and telopeptide", "of helical and telopeptide lysines", "and telopeptide lysines royce", "telopeptide lysines royce &", "lysines royce & barnes", "& barnes 1985 knott", "barnes 1985 knott et", "1985 knott et al.1997", "knott et al.1997 takaluoma", "et al.1997 takaluoma et", "al.1997 takaluoma et al.", "et al. 2007 myllyla", "al. 2007 myllyla 2007", "2007 myllyla 2007 .", "myllyla 2007 . the chemistry", "2007 . the chemistry of", ". the chemistry of the", "the chemistry of the cross", "chemistry of the cross links", "of the cross links formed", "the cross links formed depends", "cross links formed depends on", "links formed depends on whether", "formed depends on whether lysines", "depends on whether lysines or", "on whether lysines or hydroxylysines", "whether lysines or hydroxylysines are", "lysines or hydroxylysines are present", "or hydroxylysines are present in", "hydroxylysines are present in the", "are present in the telopeptides", "in the telopeptides barnes", "the telopeptides barnes et", "telopeptides barnes et al.", "al. 1974 which", "1974 which depends", "which depends on the proportion", "depends on the proportion of", "on the proportion of collagen", "the proportion of collagen lysines", "proportion of collagen lysines post", "of collagen lysines post translationally", "collagen lysines post translationally converted", "lysines post translationally converted to", "post translationally converted to hydroxylysine", "translationally converted to hydroxylysine by", "converted to hydroxylysine by lh.", "to hydroxylysine by lh. the", "hydroxylysine by lh. the lysine", "by lh. the lysine pathway", "lh. the lysine pathway predominates", "the lysine pathway predominates in", "lysine pathway predominates in adult", "pathway predominates in adult skin", "in adult skin cornea", "adult skin cornea and", "skin cornea and sclera", "cornea and sclera while the", "and sclera while the hydroxylysine", "sclera while the hydroxylysine pathway", "while the hydroxylysine pathway occurs", "the hydroxylysine pathway occurs primarily", "hydroxylysine pathway occurs primarily in", "pathway occurs primarily in bone", "primarily in bone cartilage", "bone cartilage ligament", "cartilage ligament tendons", "ligament tendons embryonic", "tendons embryonic skin and", "embryonic skin and most connective", "skin and most connective tissues", "most connective tissues eyre", "connective tissues eyre 1987", "eyre 1987 eyre &", "1987 eyre & wu", "& wu 2005 eyre", "wu 2005 eyre et", "2005 eyre et al.", "eyre et al. 2008 .", "et al. 2008 . oxidative", "al. 2008 . oxidative deamination", "2008 . oxidative deamination of", ". oxidative deamination of lysine", "oxidative deamination of lysine or", "deamination of lysine or hydroxylysine", "of lysine or hydroxylysine residues", "lysine or hydroxylysine residues by", "or hydroxylysine residues by lox", "hydroxylysine residues by lox generates", "residues by lox generates the", "by lox generates the allysine", "lox generates the allysine and", "generates the allysine and hydroxyallysine", "the allysine and hydroxyallysine aldehydes", "allysine and hydroxyallysine aldehydes respectively.", "and hydroxyallysine aldehydes respectively. these", "hydroxyallysine aldehydes respectively. these can", "aldehydes respectively. these can spontaneously", "respectively. these can spontaneously react", "these can spontaneously react with", "can spontaneously react with either", "spontaneously react with either another", "react with either another aldehyde", "with either another aldehyde to", "either another aldehyde to form", "another aldehyde to form an", "aldehyde to form an aldol", "to form an aldol condensation", "form an aldol condensation product", "aldol condensation product intramolecular", "condensation product intramolecular cross", "product intramolecular cross link", "cross link or", "link or with", "or with an unmodified lysine", "with an unmodified lysine or", "an unmodified lysine or hydroxylysine", "unmodified lysine or hydroxylysine residue", "lysine or hydroxylysine residue to", "or hydroxylysine residue to form", "hydroxylysine residue to form intermolecular", "residue to form intermolecular cross", "to form intermolecular cross links.

the", "form intermolecular cross links.

the pathway", "intermolecular cross links.

the pathway of", "cross links.

the pathway of cross", "links.

the pathway of cross linking", "pathway of cross linking is", "of cross linking is regulated", "cross linking is regulated primarily", "linking is regulated primarily by", "is regulated primarily by the", "regulated primarily by the hydroxylation", "primarily by the hydroxylation pattern", "by the hydroxylation pattern of", "the hydroxylation pattern of telopeptide", "hydroxylation pattern of telopeptide and", "pattern of telopeptide and triple", "of telopeptide and triple helix", "telopeptide and triple helix domain", "and triple helix domain lysine", "triple helix domain lysine residues.", "helix domain lysine residues. when", "domain lysine residues. when lysine", "lysine residues. when lysine residues", "residues. when lysine residues are", "when lysine residues are the", "lysine residues are the source", "residues are the source of", "are the source of aldehydes", "the source of aldehydes formed", "source of aldehydes formed by", "of aldehydes formed by lysyl", "aldehydes formed by lysyl oxidase", "formed by lysyl oxidase the", "by lysyl oxidase the allysine", "lysyl oxidase the allysine cross", "oxidase the allysine cross linking", "the allysine cross linking pathway", "allysine cross linking pathway leads", "cross linking pathway leads to", "linking pathway leads to the", "pathway leads to the formation", "leads to the formation of", "to the formation of aldimine", "the formation of aldimine cross", "formation of aldimine cross links", "aldimine cross links eyre", "cross links eyre &", "links eyre & wu", "eyre & wu 2005 .", "& wu 2005 . these", "wu 2005 . these are", "2005 . these are stable", ". these are stable at", "these are stable at physiological", "are stable at physiological conditions", "stable at physiological conditions but", "at physiological conditions but readily", "physiological conditions but readily cleaved", "conditions but readily cleaved at", "but readily cleaved at acid", "readily cleaved at acid ph", "cleaved at acid ph or", "at acid ph or elevated", "acid ph or elevated temperature.", "ph or elevated temperature. when", "or elevated temperature. when hydroxylysine", "elevated temperature. when hydroxylysine residues", "temperature. when hydroxylysine residues are", "when hydroxylysine residues are the", "hydroxylysine residues are the source", "by lysyl oxidase the hydroxyallysine", "lysyl oxidase the hydroxyallysine cross", "oxidase the hydroxyallysine cross linking", "the hydroxyallysine cross linking pathway", "hydroxyallysine cross linking pathway leads", "to the formation of more", "the formation of more stable", "formation of more stable ketoimine", "of more stable ketoimine cross", "more stable ketoimine cross links.", "stable ketoimine cross links.

telopeptide", "ketoimine cross links.

telopeptide lysine", "cross links.

telopeptide lysine residues", "links.

telopeptide lysine residues can", "

telopeptide lysine residues can be", "lysine residues can be converted", "residues can be converted by", "can be converted by lox", "be converted by lox to", "converted by lox to allysine", "lox to allysine which", "to allysine which can", "allysine which can react", "which can react with a", "can react with a helical", "react with a helical hydroxylysine", "with a helical hydroxylysine residue", "a helical hydroxylysine residue forming", "helical hydroxylysine residue forming the", "hydroxylysine residue forming the lysine", "residue forming the lysine aldehyde", "forming the lysine aldehyde aldimine", "the lysine aldehyde aldimine cross", "lysine aldehyde aldimine cross link", "aldehyde aldimine cross link dehydro", "aldimine cross link dehydro hydroxylysino", "cross link dehydro hydroxylysino norleucine", "dehydro hydroxylysino norleucine dehhlnl", "dehhlnl bailey &", "& peach 1968 eyre", "peach 1968 eyre et", "1968 eyre et al.", "et al. 2008 . if", "al. 2008 . if the", "2008 . if the telopeptide", ". if the telopeptide residue", "if the telopeptide residue is", "the telopeptide residue is hydroxylysine", "residue is hydroxylysine the", "is hydroxylysine the hydroxyallysine", "hydroxylysine the hydroxyallysine formed", "the hydroxyallysine formed by lox", "hydroxyallysine formed by lox can", "formed by lox can react", "by lox can react with", "lox can react with a", "with a helical hydroxylysine forming", "a helical hydroxylysine forming the", "helical hydroxylysine forming the schiff", "hydroxylysine forming the schiff base", "the schiff base which", "schiff base which spontaneously", "base which spontaneously undergoes", "which spontaneously undergoes an amadori", "spontaneously undergoes an amadori rearrangement", "undergoes an amadori rearrangement resulting", "an amadori rearrangement resulting in", "amadori rearrangement resulting in the", "rearrangement resulting in the ketoimine", "resulting in the ketoimine cross", "in the ketoimine cross link", "the ketoimine cross link hydroxylysino", "ketoimine cross link hydroxylysino 5", "cross link hydroxylysino 5 ketonorleucine", "hydroxylysino 5 ketonorleucine hlknl", "5 ketonorleucine hlknl .", "ketonorleucine hlknl . this", "hlknl . this stable cross", ". this stable cross link", "this stable cross link is", "stable cross link is formed", "cross link is formed in", "link is formed in tissues", "is formed in tissues where", "formed in tissues where telopeptide", "in tissues where telopeptide residues", "tissues where telopeptide residues are", "where telopeptide residues are predominanly", "telopeptide residues are predominanly hydroxylated", "are predominanly hydroxylated such", "predominanly hydroxylated such as", "hydroxylated such as foetal", "such as foetal bone and", "as foetal bone and cartilage", "bone and cartilage accounting", "and cartilage accounting for", "cartilage accounting for the", "accounting for the relative insolubility", "for the relative insolubility of", "the relative insolubility of collagen", "relative insolubility of collagen from", "insolubility of collagen from these", "of collagen from these tissues", "from these tissues bailey", "these tissues bailey et", "tissues bailey et al.", "bailey et al. 1998 .", "et al. 1998 . in", "al. 1998 . in bone", ". in bone telopeptide", "in bone telopeptide hydroxyallysines", "bone telopeptide hydroxyallysines can", "telopeptide hydroxyallysines can react with", "hydroxyallysines can react with the", "can react with the epsilon", "react with the epsilon amino", "with the epsilon amino group", "the epsilon amino group of", "epsilon amino group of a", "amino group of a helical", "group of a helical lysine", "a helical lysine robins", "helical lysine robins &", "lysine robins & bailey", "robins & bailey 1975 .", "& bailey 1975 . the", "bailey 1975 . the resulting", "1975 . the resulting schiff", ". the resulting schiff base", "the resulting schiff base undergoes", "resulting schiff base undergoes amadori", "schiff base undergoes amadori rearrangement", "base undergoes amadori rearrangement to", "undergoes amadori rearrangement to form", "amadori rearrangement to form lysino", "rearrangement to form lysino hydroxynorleucine", "form lysino hydroxynorleucine lhnl", "lysino hydroxynorleucine lhnl .", "hydroxynorleucine lhnl . an", "lhnl . an alternative mechanism", ". an alternative mechanism of", "an alternative mechanism of maturation", "alternative mechanism of maturation of", "mechanism of maturation of ketoimine", "of maturation of ketoimine cross", "maturation of ketoimine cross links", "of ketoimine cross links has", "ketoimine cross links has been", "cross links has been reported", "links has been reported in", "has been reported in cartilage", "been reported in cartilage leading", "reported in cartilage leading to", "in cartilage leading to the", "cartilage leading to the formation", "leading to the formation of", "to the formation of arginoline", "formation of arginoline eyre", "of arginoline eyre et", "arginoline eyre et al.", "eyre et al. 2010 .", "et al. 2010 .

these", "al. 2010 .

these divalent", "2010 .

these divalent crosslinks", ".

these divalent crosslinks greatly", "

these divalent crosslinks greatly diminish", "divalent crosslinks greatly diminish as", "crosslinks greatly diminish as connective", "greatly diminish as connective tissues", "diminish as connective tissues mature", "connective tissues mature due", "tissues mature due to", "mature due to further", "due to further spontaneous reactions", "further spontaneous reactions bailey", "spontaneous reactions bailey &", "reactions bailey & shimokomaki", "& shimokomaki 1971 robins", "shimokomaki 1971 robins &", "1971 robins & bailey", "& bailey 1973 with", "bailey 1973 with neighbouring", "1973 with neighbouring peptides", "with neighbouring peptides that result", "neighbouring peptides that result in", "peptides that result in tri", "result in tri and", "in tri and tetrafunctional", "tri and tetrafunctional cross", "and tetrafunctional cross links. in", "tetrafunctional cross links. in mature", "cross links. in mature tissues", "links. in mature tissues collagen", "in mature tissues collagen cross", "mature tissues collagen cross links", "tissues collagen cross links are", "collagen cross links are predominantly", "cross links are predominantly trivalent.", "links are predominantly trivalent. the", "are predominantly trivalent. the most", "predominantly trivalent. the most common", "trivalent. the most common are", "the most common are pyridinoline", "most common are pyridinoline or", "common are pyridinoline or 3", "are pyridinoline or 3 hydroxypyridinium", "pyridinoline or 3 hydroxypyridinium cross", "or 3 hydroxypyridinium cross links", "hydroxypyridinium cross links namely", "cross links namely hydroxylysyl", "links namely hydroxylysyl pyridinoline", "namely hydroxylysyl pyridinoline hl", "hydroxylysyl pyridinoline hl pyr", "pyr and lysyl", "lysyl pyridinoline l pyr", "l pyr cross links", "cross links eyre 1987", "eyre 1987 ogawa et", "1987 ogawa et al.", "et al. 1982 fujimoto", "al. 1982 fujimoto et", "1982 fujimoto et al.", "fujimoto et al. 1978 .", "et al. 1978 . hl", "al. 1978 . hl pyr", "1978 . hl pyr is", ". hl pyr is formed", "hl pyr is formed from", "pyr is formed from three", "is formed from three hydroxylysine", "formed from three hydroxylysine residues", "three hydroxylysine residues hlknl", "hydroxylysine residues hlknl plus", "residues hlknl plus a", "hlknl plus a further hydroxyallysine.", "plus a further hydroxyallysine. it", "a further hydroxyallysine. it predominates", "further hydroxyallysine. it predominates in", "hydroxyallysine. it predominates in highly", "it predominates in highly hydroxylated", "predominates in highly hydroxylated collagens", "in highly hydroxylated collagens such", "highly hydroxylated collagens such as", "hydroxylated collagens such as type", "collagens such as type ii", "such as type ii collagen", "as type ii collagen in", "type ii collagen in cartilage.", "ii collagen in cartilage. l", "collagen in cartilage. l pyr", "in cartilage. l pyr is", "cartilage. l pyr is formed", "l pyr is formed from", "pyr is formed from two", "is formed from two hydroxylysines", "formed from two hydroxylysines and", "from two hydroxylysines and a", "two hydroxylysines and a lysine", "and a lysine lknl", "a lysine lknl plus", "lysine lknl plus a", "lknl plus a further hydroxyallysine", "a further hydroxyallysine found", "further hydroxyallysine found mostly", "hydroxyallysine found mostly in", "found mostly in calcified tissues", "in calcified tissues bailey", "calcified tissues bailey et", "et al. 1998 . trivalent", "al. 1998 . trivalent collagen", "1998 . trivalent collagen cross", ". trivalent collagen cross links", "trivalent collagen cross links can", "collagen cross links can also", "cross links can also form", "links can also form as", "can also form as pyrroles", "form as pyrroles either", "as pyrroles either lysyl", "pyrroles either lysyl pyrrole", "either lysyl pyrrole l", "lysyl pyrrole l pyrrole", "l pyrrole or hydroxylysyl", "pyrrole or hydroxylysyl pyrrole", "or hydroxylysyl pyrrole hl", "hydroxylysyl pyrrole hl pyrrole", "hl pyrrole respectively", "pyrrole respectively formed", "respectively formed when lknl or", "formed when lknl or hlknl", "when lknl or hlknl react", "lknl or hlknl react with", "or hlknl react with allysine", "react with allysine scott", "with allysine scott et", "allysine scott et al.", "et al. 1981 kuypers", "al. 1981 kuypers et", "1981 kuypers et al.", "kuypers et al. 1992 .", "et al. 1992 . a", "al. 1992 . a further", "1992 . a further three", ". a further three way", "a further three way crosslink", "further three way crosslink can", "three way crosslink can form", "way crosslink can form when", "crosslink can form when deh", "can form when deh hlnl", "form when deh hlnl reacts", "when deh hlnl reacts with", "deh hlnl reacts with histidine", "hlnl reacts with histidine to", "reacts with histidine to form", "with histidine to form histidino", "histidine to form histidino hydroxylysinonorleucine", "form histidino hydroxylysinonorleucine hhl", "hhl found in", "found in skin and cornea", "skin and cornea yamauchi", "and cornea yamauchi et", "cornea yamauchi et al.", "et al. 1987 1996", "al. 1987 1996 .", "1987 1996 . this", "1996 . this can react", ". this can react with", "this can react with an", "can react with an additional", "react with an additional lysine", "with an additional lysine to", "an additional lysine to form", "additional lysine to form the", "lysine to form the tetrafunctional", "to form the tetrafunctional cross", "form the tetrafunctional cross link", "the tetrafunctional cross link histidinohydroxymerodesmosine", "cross link histidinohydroxymerodesmosine reiser", "link histidinohydroxymerodesmosine reiser et", "histidinohydroxymerodesmosine reiser et al.", "et al. 1992 yamauchi", "al. 1992 yamauchi et", "1992 yamauchi et al.", "yamauchi et al. 1996 .", "et al. 1996 .
", "al. 1996 .

another", "1996 .

another mechanism", ".

another mechanism which", "

another mechanism which could", "
another mechanism which could be", "mechanism which could be involved", "which could be involved in", "could be involved in the", "be involved in the cross", "involved in the cross linking", "in the cross linking of", "the cross linking of collagen", "cross linking of collagen iv", "linking of collagen iv networks", "of collagen iv networks is", "collagen iv networks is the", "iv networks is the sulfilimine", "networks is the sulfilimine bond", "the sulfilimine bond vanacore", "sulfilimine bond vanacore et", "bond vanacore et al.", "al. 2009 catalyzed", "2009 catalyzed by", "catalyzed by peroxidasin an", "by peroxidasin an enzyme", "peroxidasin an enzyme found", "an enzyme found in basement", "enzyme found in basement membrane", "in basement membrane bhave", "basement membrane bhave 2012", "membrane bhave 2012 .

to", "bhave 2012 .

to improve clarity", "2012 .

to improve clarity inter", ".

to improve clarity inter chain", "improve clarity inter chain cross", "clarity inter chain cross linking", "inter chain cross linking is", "chain cross linking is represented", "cross linking is represented here", "linking is represented here for", "is represented here for collagen", "represented here for collagen type", "here for collagen type i", "for collagen type i only.", "collagen type i only. although", "type i only. although the", "i only. although the formation", "only. although the formation of", "although the formation of each", "the formation of each type", "formation of each type of", "of each type of cross", "each type of cross link", "type of cross link is", "of cross link is represented", "cross link is represented here", "link is represented here as", "is represented here as an", "represented here as an independent", "here as an independent event", "an independent event the", "independent event the partial", "event the partial and", "the partial and random nature", "partial and random nature of", "and random nature of lysine", "random nature of lysine hydroxylation", "nature of lysine hydroxylation and", "of lysine hydroxylation and subsequent", "lysine hydroxylation and subsequent lysyl", "hydroxylation and subsequent lysyl oxidation", "and subsequent lysyl oxidation means", "subsequent lysyl oxidation means that", "lysyl oxidation means that any", "oxidation means that any combination", "means that any combination of", "that any combination of these", "any combination of these cross", "combination of these cross linking", "of these cross linking events", "these cross linking events could", "cross linking events could occur", "linking events could occur within", "events could occur within the", "could occur within the same", "occur within the same collagen", "within the same collagen fibril", "the same collagen fibril ." ] }, { "record_id": "GLY_000594_1_893", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2299718", "r hsa", "hsa 2299718", "r hsa 2299718" ] }, { "record_id": "GLY_000594_1_893", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "condensation of", "of prophase", "prophase chromosomes", "condensation of prophase", "of prophase chromosomes", "condensation of prophase chromosomes", "in mitotic", "mitotic prophase", "the action", "action of", "of the", "the condensin", "condensin ii", "ii complex", "complex enables", "enables initial", "initial chromosome", "chromosome condensation.

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condensin", ".

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condensin", "al. 2010 .

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two", "al. 2008 .

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holzenberger 2012", "2012 holzenberger 2012 ." ] }, { "record_id": "GLY_000594_1_895", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2408522", "r hsa", "hsa 2408522", "r hsa 2408522" ] }, { "record_id": "GLY_000594_1_895", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "selenoamino acid", "acid metabolism", "selenoamino acid metabolism", "is a", "a trace", "trace element", "element essential", "essential for", "for the", "the normal", "normal function", "function of", "of the", "the body.", "selenoamino acids", "acids are", "are defined", "defined as", "as those", "those amino", "amino acids", "acids where", "where selenium", "selenium has", "has been", "been substituted", "substituted for", "for sulphur.", "selenium and", "and sulphur", "sulphur share", "share many", "many chemical", "chemical properties", "properties and", "and so", "so the", "the substitution", "substitution of", "of 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all", "sec .

all nutritional", ".

all nutritional selenium", "nutritional selenium is", "selenium is metabolised", "is metabolised into", "metabolised into selenide", "into selenide directly", "selenide directly or", "directly or through", "or through methylselenol", "methylselenol meseh", ". sec", "sec liberated from", "liberated from selenoproteins", "from selenoproteins is", "selenoproteins is transformed", "is transformed to", "transformed to se", "to se 2", "by selenocysteine lyase", "lyase scly", ". semet", "semet liberated from", "liberated from general", "from general proteins", "general proteins and", "proteins and from", "and from free", "from free semet", "free semet sources", "semet sources is", "sources is transformed", "is transformed into", "transformed into se", "into se 2", "either through meseh", "through meseh by", "meseh by cystathionine", "by cystathionine gamma", "cystathionine gamma lyase", "lyase cth", "cth followed", "followed by demethylation", "demethylation semet", "semet to ch3seh", "to ch3seh to", "ch3seh to h2se", "or through sec", "through sec by", "sec by scly", "by scly after", "scly after the", "after the trans", "the trans selenation", "trans selenation pathway", "pathway semet", "semet to sec", "to sec to", "sec to h2se", "to h2se .", "h2se . mesec", ". mesec is", "mesec is hydrolysed", "is hydrolysed into", "hydrolysed into meseh", "into meseh by", "meseh by cth.", "cth. methylseleninic", "acid meseo2h", "meseo2h is", "is reduced to", "reduced to methylselenol.", "to methylselenol. meseh", "methylselenol. meseh is", "meseh is demethylated", "is demethylated to", "demethylated to se", "for further utilization", "further utilization for", "utilization for selenoprotein", "for selenoprotein synthesis", "selenoprotein synthesis or", "synthesis or oxidised", "or oxidised to", "oxidised to selenite", "for excretion in", "excretion in the", "in the form", "the form of", "form of selenosugar.", "of selenosugar. additionally", "additionally meseh", "meseh is further", "is further methylated", "further methylated to", "methylated to dimethylselenide", "dimethylselenide me2se", "me2se and", "trimethylselenonium me3se+", "me3se+ for", "se is a", "is a trace element", "a trace element essential", "trace element essential for", "element essential for the", "essential for the normal", "for the normal function", "the normal function of", "normal function of the", "function of the body.", "the body. selenoamino", "body. selenoamino acids", "selenoamino acids are defined", "acids are defined as", "are defined as those", "defined as those amino", "as those amino acids", "those amino acids where", "amino acids where selenium", "acids where selenium has", "where selenium has been", "selenium has been substituted", "has been substituted for", "been substituted for sulphur.", "for sulphur. selenium", "sulphur. selenium and", "selenium and sulphur share", "and sulphur share many", "sulphur share many chemical", "share many chemical properties", "many chemical properties and", "chemical properties and so", "properties and so the", "and so the substitution", "so the substitution of", "the substitution of normal", "substitution of normal amino", "of normal amino acids", "normal amino acids with", "amino acids with selenoamino", "acids with selenoamino acids", "with selenoamino acids has", "selenoamino acids has little", "acids has little effect", "has little effect on", "little effect on protein", "effect on protein structure", "on protein structure and", "protein structure and function.", "and function. both", "function. both inorganic", "both inorganic selenite", "selenite seo3 2", "and selenate seo4", "selenate seo4 2", "and organic selenocysteine", "sec and selenomethionine", "and selenomethionine semet", "semet forms of", "forms of selenium can", "of selenium can be", "selenium can be introduced", "can be introduced in", "be introduced in the", "introduced in the diet", "in the diet where", "the diet where they", "diet where they are", "where they are transformed", "they are transformed into", "are transformed into the", "transformed into the intermediate", "into the intermediate selenide", "intermediate selenide se", "selenide se 2", "and then utilized for", "then utilized for the", "utilized for the de", "for the de novo", "the de novo synthesis", "de novo synthesis of", "novo synthesis of sec", "synthesis of sec through", "of sec through a", "sec through a phosphorylated", "through a phosphorylated intermediate", "a phosphorylated intermediate in", "phosphorylated intermediate in a", "intermediate in a trna", "in a trna dependent", "a trna dependent fashion.", "trna dependent fashion. the", "dependent fashion. the final", "fashion. the final step", "the final step of", "final step of sec", "step of sec formation", "of sec formation is", "sec formation is catalyzed", "formation is catalyzed by", "is catalyzed by o", "catalyzed by o phosphoseryl", "by o phosphoseryl trna:selenocysteinyl", "o phosphoseryl trna:selenocysteinyl trna", "phosphoseryl trna:selenocysteinyl trna synthase", "trna synthase sepsecs", "sepsecs that converts", "that converts phosphoseryl trna", "converts phosphoseryl trna sec", "trna sec to", "sec to selenocysteinyl", "to selenocysteinyl trna sec", "selenocysteinyl trna sec .

all", "trna sec .

all nutritional", "sec .

all nutritional selenium", ".

all nutritional selenium is", "nutritional selenium is metabolised", "selenium is metabolised into", "is metabolised into selenide", "metabolised into selenide directly", "into selenide directly or", "selenide directly or through", "directly or through methylselenol", "through methylselenol meseh", "methylselenol meseh .", "meseh . sec", ". sec liberated", "sec liberated from selenoproteins", "liberated from selenoproteins is", "from selenoproteins is transformed", "selenoproteins is transformed to", "is transformed to se", "transformed to se 2", "2 by", "selenocysteine lyase scly", "lyase scly .", "scly . semet", ". semet liberated", "semet liberated from general", "liberated from general proteins", "from general proteins and", "general proteins and from", "proteins and from free", "and from free semet", "from free semet sources", "free semet sources is", "semet sources is transformed", "sources is transformed into", "is transformed into se", "transformed into se 2", "2 either", "either through meseh by", "through meseh by cystathionine", "meseh by cystathionine gamma", "by cystathionine gamma lyase", "gamma lyase cth", "cth followed by", "by demethylation semet", "demethylation semet to", "semet to ch3seh to", "to ch3seh to h2se", "h2se or", "or through sec by", "through sec by scly", "sec by scly after", "by scly after the", "scly after the trans", "after the trans selenation", "the trans selenation pathway", "selenation pathway semet", "pathway semet to", "semet to sec to", "to sec to h2se", "sec to h2se .", "to h2se . mesec", "h2se . mesec is", ". mesec is hydrolysed", "mesec is hydrolysed into", "is hydrolysed into meseh", "hydrolysed into meseh by", "into meseh by cth.", "by cth. methylseleninic", "cth. methylseleninic acid", "methylseleninic acid meseo2h", "meseo2h is reduced", "is reduced to methylselenol.", "reduced to methylselenol. meseh", "to methylselenol. meseh is", "methylselenol. meseh is demethylated", "meseh is demethylated to", "is demethylated to se", "demethylated to se 2", "2 for", "for further utilization for", "further utilization for selenoprotein", "utilization for selenoprotein synthesis", "for selenoprotein synthesis or", "selenoprotein synthesis or oxidised", "synthesis or oxidised to", "or oxidised to selenite", "to selenite seo3", "for excretion in the", "excretion in the form", "in the form of", "the form of selenosugar.", "form of selenosugar. additionally", "selenosugar. additionally meseh", "additionally meseh is", "meseh is further methylated", "is further methylated to", "further methylated to dimethylselenide", "to dimethylselenide me2se", "me2se and trimethylselenonium", "and trimethylselenonium me3se+", "me3se+ for excretion.", "selenium se is", "se is a trace", "is a trace element essential", "a trace element essential for", "trace element essential for the", "element essential for the normal", "essential for the normal function", "for the normal function of", "the normal function of the", "normal function of the body.", "of the body. selenoamino", "the body. selenoamino acids", "body. selenoamino acids are", "selenoamino acids are defined as", "acids are defined as those", "are defined as those amino", "defined as those amino acids", "as those amino acids where", "those amino acids where selenium", "amino acids where selenium has", "acids where selenium has been", "where selenium has been substituted", "selenium has been substituted for", "has been substituted for sulphur.", "substituted for sulphur. selenium", "for sulphur. selenium and", "sulphur. selenium and sulphur", "selenium and sulphur share many", "and sulphur share many chemical", "sulphur share many chemical properties", "share many chemical properties and", "many chemical properties and so", "chemical properties and so the", "properties and so the substitution", "and so the substitution of", "so the substitution of normal", "the substitution of normal amino", "substitution of normal amino acids", "of normal amino acids with", "normal amino acids with selenoamino", "amino acids with selenoamino acids", "acids with selenoamino acids has", "with selenoamino acids has little", "selenoamino acids has little effect", "acids has little effect on", "has little effect on protein", "little effect on protein structure", "effect on protein structure and", "on protein structure and function.", "structure and function. both", "and function. both inorganic", "inorganic selenite seo3", "2 and", "and selenate seo4 2", "organic selenocysteine sec", "selenocysteine sec and", "selenomethionine semet forms", "semet forms of selenium", "forms of selenium can be", "of selenium can be introduced", "selenium can be introduced in", "can be introduced in the", "be introduced in the diet", "introduced in the diet where", "in the diet where they", "the diet where they are", "diet where they are transformed", "where they are transformed into", "they are transformed into the", "are transformed into the intermediate", "transformed into the intermediate selenide", "the intermediate selenide se", "intermediate selenide se 2", "and then utilized for the", "then utilized for the de", "utilized for the de novo", "for the de novo synthesis", "the de novo synthesis of", "de novo synthesis of sec", "novo synthesis of sec through", "synthesis of sec through a", "of sec through a phosphorylated", "sec through a phosphorylated intermediate", "through a phosphorylated intermediate in", "a phosphorylated intermediate in a", "phosphorylated intermediate in a trna", "intermediate in a trna dependent", "in a trna dependent fashion.", "a trna dependent fashion. the", "trna dependent fashion. the final", "dependent fashion. the final step", "fashion. the final step of", "the final step of sec", "final step of sec formation", "step of sec formation is", "of sec formation is catalyzed", "sec formation is catalyzed by", "formation is catalyzed by o", "is catalyzed by o phosphoseryl", "catalyzed by o phosphoseryl trna:selenocysteinyl", "by o phosphoseryl trna:selenocysteinyl trna", "o phosphoseryl trna:selenocysteinyl trna synthase", "trna:selenocysteinyl trna synthase sepsecs", "synthase sepsecs that", "sepsecs that converts phosphoseryl", "that converts phosphoseryl trna sec", "phosphoseryl trna sec to", "trna sec to selenocysteinyl", "sec to selenocysteinyl trna", "to selenocysteinyl trna sec .

all", "selenocysteinyl trna sec .

all nutritional", "trna sec .

all nutritional selenium", "sec .

all nutritional selenium is", ".

all nutritional selenium is metabolised", "nutritional selenium is metabolised into", "selenium is metabolised into selenide", "is metabolised into selenide directly", "metabolised into selenide directly or", "into selenide directly or through", "selenide directly or through methylselenol", "or through methylselenol meseh", "through methylselenol meseh .", "meseh . sec liberated", ". sec liberated from", "sec liberated from selenoproteins is", "liberated from selenoproteins is transformed", "from selenoproteins is transformed to", "selenoproteins is transformed to se", "is transformed to se 2", "se 2 by", "2 by selenocysteine", "by selenocysteine lyase scly", "selenocysteine lyase scly .", "scly . semet liberated", ". semet liberated from", "semet liberated from general proteins", "liberated from general proteins and", "from general proteins and from", "general proteins and from free", "proteins and from free semet", "and from free semet sources", "from free semet sources is", "free semet sources is transformed", "semet sources is transformed into", "sources is transformed into se", "is transformed into se 2", "se 2 either", "2 either through", "either through meseh by cystathionine", "through meseh by cystathionine gamma", "meseh by cystathionine gamma lyase", "cystathionine gamma lyase cth", "lyase cth followed", "cth followed by demethylation", "followed by demethylation semet", "by demethylation semet to", "demethylation semet to ch3seh", "semet to ch3seh to h2se", "to h2se or", "h2se or through", "or through sec by scly", "through sec by scly after", "sec by scly after the", "by scly after the trans", "scly after the trans selenation", "after the trans selenation pathway", "trans selenation pathway semet", "selenation pathway semet to", "pathway semet to sec", "semet to sec to h2se", "to sec to h2se .", "sec to h2se . mesec", "to h2se . mesec is", "h2se . mesec is hydrolysed", ". mesec is hydrolysed into", "mesec is hydrolysed into meseh", "is hydrolysed into meseh by", "hydrolysed into meseh by cth.", "meseh by cth. methylseleninic", "by cth. methylseleninic acid", "acid meseo2h is", "meseo2h is reduced to", "is reduced to methylselenol. meseh", "reduced to methylselenol. meseh is", "to methylselenol. meseh is demethylated", "methylselenol. meseh is demethylated to", "meseh is demethylated to se", "is demethylated to se 2", "se 2 for", "2 for further", "for further utilization for selenoprotein", "further utilization for selenoprotein synthesis", "utilization for selenoprotein synthesis or", "for selenoprotein synthesis or oxidised", "selenoprotein synthesis or oxidised to", "synthesis or oxidised to selenite", "oxidised to selenite seo3", "to selenite seo3 2", "for excretion in the form", "excretion in the form of", "in the form of selenosugar.", "the form of selenosugar. additionally", "of selenosugar. additionally meseh", "selenosugar. additionally meseh is", "additionally meseh is further", "meseh is further methylated to", "is further methylated to dimethylselenide", "methylated to dimethylselenide me2se", "dimethylselenide me2se and", "trimethylselenonium me3se+ for" ] }, { "record_id": "GLY_000594_1_896", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2408550", "r hsa", "hsa 2408550", "r hsa 2408550" ] }, { "record_id": "GLY_000594_1_896", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "metabolism of", "of ingested", "ingested h2seo4", "h2seo4 and", "and h2seo3", "h2seo3 into", "into h2se", "metabolism of ingested", "of ingested h2seo4", "ingested h2seo4 and", "h2seo4 and h2seo3", "and h2seo3 into", "h2seo3 into h2se", "metabolism of ingested h2seo4", "of ingested h2seo4 and", "ingested h2seo4 and h2seo3", "h2seo4 and h2seo3 into", "and h2seo3 into h2se", "metabolism of ingested h2seo4 and", "of ingested h2seo4 and h2seo3", "ingested h2seo4 and h2seo3 into", "h2seo4 and h2seo3 into h2se", "ingested selenic", "selenic acid", "and selenite", "seo3 2", "are reduced", "reduced to", "to hydrogen", "hydrogen selenide", "through a", "a combination", "combination of", "of actions", "actions involving", "involving bifunctional", "bifunctional 3'", "3' phosphoadenosine", "phosphoadenosine 5'", "5' phosphosulfate", "phosphosulfate synthase", "synthase 1", "1 and", "and 2", "papse reductase", "and thioredoxin", "thioredoxin reductase", "reductase 1", "txnrd1 .", "ingested selenic acid", "acid h2seo4", "selenite seo3", "are reduced to", "reduced to hydrogen", "to hydrogen selenide", "selenide h2se", "h2se through", "through a combination", "a combination of", "combination of actions", "of actions involving", "actions involving bifunctional", "involving bifunctional 3'", "bifunctional 3' phosphoadenosine", "3' phosphoadenosine 5'", "phosphoadenosine 5' phosphosulfate", "5' phosphosulfate synthase", "phosphosulfate synthase 1", "synthase 1 and", "1 and 2", "2 papss1/2", "reductase papser", "and thioredoxin 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"fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2428933", "r hsa", "hsa 2428933", "r hsa 2428933" ] }, { "record_id": "GLY_000594_1_898", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc related", "related events", "events triggered", "triggered by", "by igf1r", "shc related events", "related events triggered", "events triggered by", "triggered by igf1r", "shc related events triggered", "related events triggered by", "events triggered by igf1r", "shc related events triggered by", "related events triggered by igf1r", "phosphorylated igf1r", "igf1r binds", "binds and", "and phosphorylates", "phosphorylates shc1", "reviewed in", "in pavelic", "pavelic et", "et al.", "al. 2007", "chitnis et", "al. 2008", "maki et", "al. 2010", "parrella et", "siddle et", "al. 2012", "2012 .", ". phosphorylated", "phosphorylated shc", "shc then", "then binds", "binds grb:sos", "which activates", "activates ras", "ras raf", "raf mapk", "mapk signaling.", 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2010", "al. 2010 siddle", "2010 siddle et", "siddle et al. 2012", "et al. 2012 .", "al. 2012 . phosphorylated", "2012 . phosphorylated shc", ". phosphorylated shc then", "phosphorylated shc then binds", "shc then binds grb:sos", "binds grb:sos which", "grb:sos which activates", "which activates ras raf", "activates ras raf mapk", "ras raf mapk signaling.", "phosphorylated igf1r binds and phosphorylates", "igf1r binds and phosphorylates shc1", "and phosphorylates shc1 reviewed", "phosphorylates shc1 reviewed in", "shc1 reviewed in pavelic", "reviewed in pavelic et al.", "in pavelic et al. 2007", "et al. 2007 chitnis", "al. 2007 chitnis et", "2007 chitnis et al.", "et al. 2008 maki", "al. 2008 maki et", "2008 maki et al.", "et al. 2010 parrella", "al. 2010 parrella et", "2010 parrella et al.", "et al. 2010 siddle", "al. 2010 siddle et", "2010 siddle et al.", "siddle et al. 2012 .", "et al. 2012 . phosphorylated", "al. 2012 . phosphorylated shc", "2012 . phosphorylated shc then", ". phosphorylated shc then binds", "phosphorylated shc then binds grb:sos", "then binds grb:sos which", "binds grb:sos which activates", "grb:sos which activates ras", "which activates ras raf mapk", "activates ras raf mapk signaling." ] }, { "record_id": "GLY_000594_1_899", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2465910", "r hsa", "hsa 2465910", "r hsa 2465910" ] }, { "record_id": "GLY_000594_1_899", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mastl facilitates", "facilitates mitotic", "mitotic progression", "mastl facilitates mitotic", "facilitates mitotic progression", "mastl facilitates mitotic progression", "the activity", "activity of", "of mastl", "also known", "known as", "as the", "the greatwall", "greatwall kinase", "is necessary", "necessary for", "for the", "the entry", "entry and", "and progression", "progression of", "of mitosis.", "mitosis. mastl", "mastl is", "is activated", "activated by", "by phosphorylation", "phosphorylation of", "of several", "several key", "key residues", "residues during", "during mitotic", "mitotic entry.", "entry. phosphorylation", "phosphorylation on", "on the", "the serine", "serine residue", "residue s875", "s883 in", "in xenopus", "likely through", "through autophosphorylation", "blake hodek", "hodek et", "et al.", "al. 2012", "appears to", "to be", "be critical", "vigneron et", "al. 2011", "2011 .", ". several", "several other", "other sites", "including putative", "putative cdk1", "cdk1 targets", "targets t194", "t207 and", "and t741", "contribute to", "to the", "the full", "full activation", "activation of", "yu et", "al. 2006", "2012 .", ". other", "other kinases", "such as", "as plk1", "and other", "other mastl", "mastl phosphorylation", "phosphorylation sites", "sites may", "may also", "also be", "be functionally", "functionally important", "2012 .

activated", ".

activated mastl", "mastl phosphorylates", "phosphorylates arpp19", "arpp19 and", "and ensa", "ensa on", "on serines", "serines s62", "s62 and", "and s67", "enabling them", "them to", "to bind", "bind to", "to and", "and inhibit", "inhibit the", "the phosphatase", "phosphatase activity", "of pp2a", "pp2a complexed", "complexed with", "with the", "the regulatory", "regulatory subunit", "subunit ppp2r2d", "b55 delta", "delta .", ". inhibition", "inhibition of", "pp2a ppp2r2d", "ppp2r2d activity", "activity by", "by arpp19", "arpp19 or", "or ensa", "ensa prevents", "prevents dephosphorylation", "dephosphorylation of", "of cdk1", "hence allowing", "allowing entry", "and maintenance", "maintenance of", "of mitosis", "mochida et", "al. 2010", "gharbi ayachi", "ayachi et", "burgess et", "2010 .

", "the activity of", "activity of mastl", "mastl also", "also known as", "known as the", "as the greatwall", "the greatwall kinase", "kinase gwl", "is necessary for", "necessary for the", "for the entry", "the entry and", "entry and progression", "and progression of", "progression of mitosis.", "of mitosis. mastl", "mitosis. mastl is", "mastl is activated", "is activated by", "activated by phosphorylation", "by phosphorylation of", "phosphorylation of several", "of several key", "several key residues", "key residues during", "residues during mitotic", "during mitotic entry.", "mitotic entry. phosphorylation", "entry. phosphorylation on", "phosphorylation on the", "on the serine", "the serine residue", "serine residue s875", "s875 s883", "s883 in xenopus", "likely through autophosphorylation", "autophosphorylation blake", "blake hodek et", "hodek et al.", "et al. 2012", "2012 appears", "appears to be", "to be critical", "critical vigneron", "vigneron et al.", "et al. 2011", "al. 2011 .", "2011 . several", ". several other", "several other sites", "sites including", "including putative cdk1", "putative cdk1 targets", "cdk1 targets t194", "t194 t207", "t207 and t741", "t741 contribute", "contribute to the", "to the full", "the full activation", "full activation of", "activation of mastl", "mastl yu", "yu et al.", "et al. 2006", "2006 blake", "al. 2012 .", "2012 . other", ". other kinases", "kinases such", "such as plk1", "plk1 vigneron", "2011 and", "and other mastl", "other mastl phosphorylation", "mastl phosphorylation sites", "phosphorylation sites may", "sites may also", "may also be", "also be functionally", "be functionally important", "important yu", "al. 2012 .

activated", "2012 .

activated mastl", ".

activated mastl phosphorylates", "mastl phosphorylates arpp19", "phosphorylates arpp19 and", "arpp19 and ensa", "and ensa on", "ensa on serines", "on serines s62", "serines s62 and", "s62 and s67", "s67 respectively", "respectively enabling", "enabling them to", "them to bind", "to bind to", "bind to and", "to and inhibit", "and inhibit the", "inhibit the phosphatase", "the phosphatase activity", "phosphatase activity of", "activity of pp2a", "of pp2a complexed", "pp2a complexed with", "complexed with the", "with the regulatory", "the regulatory subunit", "regulatory subunit ppp2r2d", "ppp2r2d b55", "b55 delta .", "delta . inhibition", ". inhibition of", "inhibition of pp2a", "of pp2a ppp2r2d", "pp2a ppp2r2d activity", "ppp2r2d activity by", "activity by arpp19", "by arpp19 or", "arpp19 or ensa", "or ensa prevents", "ensa prevents dephosphorylation", "prevents dephosphorylation of", "dephosphorylation of cdk1", "of cdk1 targets", "targets hence", "hence allowing entry", "allowing entry and", "entry and maintenance", "and maintenance of", "maintenance of mitosis", "mitosis mochida", "mochida et al.", "et al. 2010", "2010 gharbi", "gharbi ayachi et", "ayachi et al.", "2010 burgess", "burgess et al.", "al. 2010 .

", "the activity of mastl", "of mastl also", "mastl also known", "also known as the", "known as the greatwall", "as the greatwall kinase", "greatwall kinase gwl", "gwl is", "is necessary for the", "necessary for the entry", "for the entry and", "the entry and progression", "entry and progression of", "and progression of mitosis.", "progression of mitosis. mastl", "of mitosis. mastl is", "mitosis. mastl is activated", "mastl is activated by", "is activated by phosphorylation", "activated by phosphorylation of", "by phosphorylation of several", "phosphorylation of several key", "of several key residues", "several key residues during", "key residues during mitotic", "residues during mitotic entry.", "during mitotic entry. phosphorylation", "mitotic entry. phosphorylation on", "entry. phosphorylation on the", "phosphorylation on the serine", "on the serine residue", "the serine residue s875", "residue s875 s883", "s875 s883 in", "xenopus likely", "through autophosphorylation blake", "autophosphorylation blake hodek", "blake hodek et al.", "hodek et al. 2012", "al. 2012 appears", "2012 appears to", "appears to be critical", "be critical vigneron", "critical vigneron et", "vigneron et al. 2011", "et al. 2011 .", "al. 2011 . several", "2011 . several other", ". several other sites", "other sites including", "sites including putative", "including putative cdk1 targets", "putative cdk1 targets t194", "targets t194 t207", "t194 t207 and", "and t741 contribute", "t741 contribute to", "contribute to the full", "to the full activation", "the full activation of", "full activation of mastl", "of mastl yu", "mastl yu et", "yu et al. 2006", "al. 2006 blake", "2006 blake hodek", "et al. 2012 .", "al. 2012 . other", "2012 . other kinases", "other kinases such", "kinases such as", "as plk1 vigneron", "plk1 vigneron et", "al. 2011 and", "2011 and other", "and other mastl phosphorylation", "other mastl phosphorylation sites", "mastl phosphorylation sites may", "phosphorylation sites may also", "sites may also be", "may also be functionally", "also be functionally important", "functionally important yu", "important yu et", "et al. 2012 .

activated", "al. 2012 .

activated mastl", "2012 .

activated mastl phosphorylates", ".

activated mastl phosphorylates arpp19", "mastl phosphorylates arpp19 and", "phosphorylates arpp19 and ensa", "arpp19 and ensa on", "and ensa on serines", "ensa on serines s62", "on serines s62 and", "serines s62 and s67", "and s67 respectively", "respectively enabling them", "enabling them to bind", "them to bind to", "to bind to and", "bind to and inhibit", "to and inhibit the", "and inhibit the phosphatase", "inhibit the phosphatase activity", "the phosphatase activity of", "phosphatase activity of pp2a", "activity of pp2a complexed", "of pp2a complexed with", "pp2a complexed with the", "complexed with the regulatory", "with the regulatory subunit", "the regulatory subunit ppp2r2d", "subunit ppp2r2d b55", "ppp2r2d b55 delta", "b55 delta . inhibition", "delta . inhibition of", ". inhibition of pp2a", "inhibition of pp2a ppp2r2d", "of pp2a ppp2r2d activity", "pp2a ppp2r2d activity by", "ppp2r2d activity by arpp19", "activity by arpp19 or", "by arpp19 or ensa", "arpp19 or ensa prevents", "or ensa prevents dephosphorylation", "ensa prevents dephosphorylation of", "prevents dephosphorylation of cdk1", "dephosphorylation of cdk1 targets", "cdk1 targets hence", "targets hence allowing", "hence allowing entry and", "allowing entry and maintenance", "entry and maintenance of", "and maintenance of mitosis", "of mitosis mochida", "mitosis mochida et", "mochida et al. 2010", "al. 2010 gharbi", "2010 gharbi ayachi", "gharbi ayachi et al.", "ayachi et al. 2010", "al. 2010 burgess", "2010 burgess et", "burgess et al. 2010", "et al. 2010 .

", "activity of mastl also", "of mastl also known", "mastl also known as", "also known as the greatwall", "known as the greatwall kinase", "the greatwall kinase gwl", "gwl is necessary", "is necessary for the entry", "necessary for the entry and", "for the entry and progression", "the entry and progression of", "entry and progression of mitosis.", "and progression of mitosis. mastl", "progression of mitosis. mastl is", "of mitosis. mastl is activated", "mitosis. mastl is activated by", "mastl is activated by phosphorylation", "is activated by phosphorylation of", "activated by phosphorylation of several", "by phosphorylation of several key", "phosphorylation of several key residues", "of several key residues during", "several key residues during mitotic", "key residues during mitotic entry.", "residues during mitotic entry. phosphorylation", "during mitotic entry. phosphorylation on", "mitotic entry. phosphorylation on the", "entry. phosphorylation on the serine", "phosphorylation on the serine residue", "on the serine residue s875", "serine residue s875 s883", "residue s875 s883 in", "s875 s883 in xenopus", "in xenopus likely", "xenopus likely through", "likely through autophosphorylation blake", "through autophosphorylation blake hodek", "autophosphorylation blake hodek et", "blake hodek et al. 2012", "et al. 2012 appears", "al. 2012 appears to", "2012 appears to be", "to be critical vigneron", "be critical vigneron et", "critical vigneron et al.", "vigneron et al. 2011 .", "et al. 2011 . several", "al. 2011 . several other", "2011 . several other sites", "several other sites including", "other sites including putative", "sites including putative cdk1", "including putative cdk1 targets t194", "cdk1 targets t194 t207", "targets t194 t207 and", "t194 t207 and t741", "t207 and t741 contribute", "and t741 contribute to", "t741 contribute to the", "contribute to the full activation", "to the full activation of", "the full activation of mastl", "activation of mastl yu", "of mastl yu et", "mastl yu et al.", "et al. 2006 blake", "al. 2006 blake hodek", "2006 blake hodek et", "hodek et al. 2012 .", "et al. 2012 . other", "al. 2012 . other kinases", ". other kinases such", "other kinases such as", "kinases such as plk1", "such as plk1 vigneron", "as plk1 vigneron et", "plk1 vigneron et al.", "et al. 2011 and", "al. 2011 and other", "2011 and other mastl", "and other mastl phosphorylation sites", "other mastl phosphorylation sites may", "mastl phosphorylation sites may also", "phosphorylation sites may also be", "sites may also be functionally", "may also be functionally important", "be functionally important yu", "functionally important yu et", "important yu et al.", "hodek et al. 2012 .

activated", "et al. 2012 .

activated mastl", "al. 2012 .

activated mastl phosphorylates", "2012 .

activated mastl phosphorylates arpp19", ".

activated mastl phosphorylates arpp19 and", "mastl phosphorylates arpp19 and ensa", "phosphorylates arpp19 and ensa on", "arpp19 and ensa on serines", "and ensa on serines s62", "ensa on serines s62 and", "on serines s62 and s67", "s62 and s67 respectively", "s67 respectively enabling", "respectively enabling them to", "enabling them to bind to", "them to bind to and", "to bind to and inhibit", "bind to and inhibit the", "to and inhibit the phosphatase", "and inhibit the phosphatase activity", "inhibit the phosphatase activity of", "the phosphatase activity of pp2a", "phosphatase activity of pp2a complexed", "activity of pp2a complexed with", "of pp2a complexed with the", "pp2a complexed with the regulatory", "complexed with the regulatory subunit", "with the regulatory subunit ppp2r2d", "regulatory subunit ppp2r2d b55", "subunit ppp2r2d b55 delta", "ppp2r2d b55 delta .", "b55 delta . inhibition of", "delta . inhibition of pp2a", ". inhibition of pp2a ppp2r2d", "inhibition of pp2a ppp2r2d activity", "of pp2a ppp2r2d activity by", "pp2a ppp2r2d activity by arpp19", "ppp2r2d activity by arpp19 or", "activity by arpp19 or ensa", "by arpp19 or ensa prevents", "arpp19 or ensa prevents dephosphorylation", "or ensa prevents dephosphorylation of", "ensa prevents dephosphorylation of cdk1", "prevents dephosphorylation of cdk1 targets", "of cdk1 targets hence", "cdk1 targets hence allowing", "targets hence allowing entry", "hence allowing entry and maintenance", "allowing entry and maintenance of", "entry and maintenance of mitosis", "maintenance of mitosis mochida", "of mitosis mochida et", "mitosis mochida et al.", "et al. 2010 gharbi", "al. 2010 gharbi ayachi", "2010 gharbi ayachi et", "gharbi ayachi et al. 2010", "et al. 2010 burgess", "al. 2010 burgess et", "2010 burgess et al.", "burgess et al. 2010 .

" ] }, { "record_id": "GLY_000594_1_900", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2468052", "r hsa", "hsa 2468052", "r hsa 2468052" ] }, { "record_id": "GLY_000594_1_900", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "establishment of", "of sister", "sister chromatid", "chromatid cohesion", "establishment of sister", "of sister chromatid", "sister chromatid cohesion", "establishment of sister chromatid", "of sister chromatid cohesion", "establishment of sister chromatid cohesion", "the cohesin", "cohesin complex", "complex loads", "loads onto", "onto chromatin", "chromatin in", "in telophase", "but its", "its association", "association with", "with chromatin", "chromatin remains", "remains transient", "dynamic until", "until the", "the s", "s phase", "phase of", "of the", "the cell", "cell cycle", "presumably because", "because the", "cohesin bound", "bound nipbl:mau2", "complex promotes", "promotes chromatin", "chromatin loading", "while cohesin", "bound wapal", "wapal promotes", "promotes dissociation", "dissociation from", "from chromatin.", "chromatin. stable", "stable binding", "binding of", "of cohesin", "cohesin complexes", "complexes to", "to chromatin", "measured by", "by a", "a mean", "mean residence", "residence time", "time on", "on chromatin", "is triggered", "triggered by", "by dna", "dna replication", "replication in", "in s", "gerlich et", "et al.", "al. 2006", "consistent with", "with establishment", "chromatid cohesion.", "cohesion.

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", "

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"filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2514853", "r hsa", "hsa 2514853", "r hsa 2514853" ] }, { "record_id": "GLY_000594_1_904", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "condensation of", "of prometaphase", "prometaphase chromosomes", "condensation of prometaphase", "of prometaphase chromosomes", "condensation of prometaphase chromosomes", "the condensin", "condensin i", "i complex", "complex is", "is evolutionarily", "evolutionarily conserved", "conserved and", "and consists", "consists of", "of five", "five subunits:", "subunits: two", "two smc", "structural maintenance", "maintenance of", "of chromosomes", "family subunits", "smc2 and", "and smc4", "and three", "three non", "non smc", "smc subunits", "ncaph and", "and ncapg.", "ncapg. the", "the stoichiometry", "stoichiometry of", "of the", "the complex", "is 1:1:1:1:1", "hirano and", "and mitchinson", "mitchinson 1994", 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protein", "

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", ".

as", "as condensin", "i is", "is cytosolic", "it gains", "gains access", "access to", "to chromosomes", "chromosomes only", "only after", "after the", "the nuclear", "nuclear envelope", "envelope breakdown", "breakdown at", "at the", "the start", "start of", "ono et", ". condensin", "activated by", "by cdk1", "cdk1 mediated", "mediated phosphorylation", "promotes hypercondensation", "hypercondensation of", "chromosomes that", "that were", "were condensed", "condensed in", "in prophase", "prophase through", "through the", "the action", "action of", "hirota et", ". aurkb", "aurkb may", "also regulate", "regulate association", "association of", "with chromatin", "lipp et", "2007 .", ". protein", "protein phosphatase", "phosphatase pp2a", "pp2a acts", "acts independently", "independently of", "of its", "its catalytic", "catalytic activity", "activity to", "to target", "target condensin", "ii complex", "complex to", "to chromatin", "but does", "does not", "not interact", "interact with", "with condensin", ". full", "full activation", "activation of", "i requires", "requires dephosphorylation", "dephosphorylation of", "of sites", "sites modified", "modified by", "by ck2", "ck2 during", "during interphase", "2006 .", ". besides", "besides being", "being essential", "essential for", "for chromosome", "chromosome condensation", "condensation in", "i may", "also contribute", "contribute to", "to cohesin", "cohesin removal", "removal from", "from chromosome", "chromosome arms", "arms in", "in prometaphase", "but the", "the exact", "exact mechanism", "mechanism is", "is not", "not known", "the condensin i", "condensin i complex", "i complex is", "complex is evolutionarily", "is evolutionarily conserved", "evolutionarily conserved and", "conserved and consists", "and consists of", "consists of five", "of five subunits:", "five subunits: two", "subunits: two smc", "smc structural", "structural maintenance of", "maintenance of chromosomes", "chromosomes family", "smc2 and smc4", "and three non", "three non smc", "non smc subunits", "ncapd2 ncaph", "ncaph and ncapg.", "and ncapg. the", "ncapg. the stoichiometry", "the stoichiometry of", "stoichiometry of the", "of the complex", "the complex is", "complex is 1:1:1:1:1", "1:1:1:1:1 hirano", "hirano and mitchinson", "and mitchinson 1994", "1994 hirano", "hirano et al.", "et al. 1997", "1997 kimura", "kimura et al.", "et al. 2001", "al. 2001 .", "2001 . smc2", ". smc2 and", "and smc4 subunits", "subunits shared", "shared between condensin", "between condensin i", "condensin i and", "i and condensin", "and condensin ii", "ii are", "are dna dependent", "dna dependent atpases", "atpases and", "and condensins are", "condensins are able", "are able to", "able to introduce", "to introduce positive", "introduce positive supercoils", "positive supercoils into", "supercoils into dna", "into dna in", "dna in an", "in an atp", "an atp dependent", "atp dependent manner", "manner kimura", "kimura and hirano", "and hirano 1997", "hirano 1997 .", "1997 .

protein", ".

protein levels", "

protein levels of", "levels of condensin", "of condensin subunits", "condensin subunits are", "subunits are constant", "are constant during", "constant during the", "during the cell", "the cell cycle", "cycle however", "however condensins are", "condensins are enriched", "are enriched on", "enriched on mitotic", "on mitotic chromosomes.", "mitotic chromosomes. four", "chromosomes. four of", "four of the", "of the five", "the five subunits", "subunits smc4", "smc4 ncapd2", "ncapd2 ncapg", "ncapg and ncaph", "are phosphorylated in", "phosphorylated in both", "in both mitotic", "both mitotic and", "mitotic and interphase", "and interphase hela", "interphase hela cells", "cells but", "but on different", "on different sites", "sites takemoto", "takemoto et al.", "et al. 2004", "al. 2004 .", "2004 . cdk1", "cdk1 cdc2", "cdc2 in", "in complex with", "complex with ccnb", "ccnb cyclin", "b phosphorylates", "and ncaph in", "ncaph in mitosis", "mitosis kimura", "et al. 1998", "1998 kimura", "2001 takemoto", "et al. 2006", "2006 murphy", "murphy et al.", "et al. 2008", "but other mitotic", "other mitotic kinases", "kinases such", "such as plk1", "plk1 st", "st pierre et", "pierre et al.", "et al. 2009", "and other post", "other post translational", "post translational modifications", "modifications such", "such as acetylation", "acetylation may", "may also be", "also be involved", "involved reviewed", "reviewed by bazile", "by bazile et", "bazile et al.", "et al. 2010", "al. 2010 .", "2010 . global", ". global proteomic", "global proteomic analysis", "proteomic analysis of", "analysis of human", "of human cell", "human cell lines", "cell lines has", "lines has identified", "has identified n6", "identified n6 acetylation", "n6 acetylation of", "acetylation of lysine", "of lysine residues", "lysine residues in", "residues in condensin", "in condensin subunits", "condensin subunits smc2", "smc2 smc4", "smc4 and ncaph", "ncaph choudhary", "choudhary et al.", "al. 2009 .", "2009 . another", ". another high", "another high throughput", "high throughput proteomic", "throughput proteomic study", "proteomic study showed", "study showed that", "showed that condensin", "that condensin i", "condensin i subunits", "i subunits ncapd2", "subunits ncapd2 and", "ncapd2 and ncaph", "and ncaph are", "ncaph are phosphorylated", "are phosphorylated upon", "phosphorylated upon dna", "upon dna damage", "damage probably", "probably by atm", "by atm or", "atm or atr", "or atr kinase", "kinase matsuoka", "matsuoka et al.", "et al. 2007", "al. 2007 .

", "2007 .

as", ".

as condensin", "as condensin i", "condensin i is", "i is cytosolic", "cytosolic it", "it gains access", "gains access to", "access to chromosomes", "to chromosomes only", "chromosomes only after", "only after the", "after the nuclear", "the nuclear envelope", "nuclear envelope breakdown", "envelope breakdown at", "breakdown at the", "at the start", "the start of", "start of prometaphase", "prometaphase ono", "ono et al.", "2004 . condensin", ". condensin i", "i activated", "activated by cdk1", "by cdk1 mediated", "cdk1 mediated phosphorylation", "phosphorylation promotes", "promotes hypercondensation of", "hypercondensation of chromosomes", "of chromosomes that", "chromosomes that were", "that were condensed", "were condensed in", "condensed in prophase", "in prophase through", "prophase through the", "through the action", "the action of", "action of condensin", "of condensin ii", "ii hirota", "hirota et al.", "2004 . aurkb", ". aurkb may", "aurkb may also", "may also regulate", "also regulate association", "regulate association of", "association of condensin", "of condensin i", "i complex with", "complex with chromatin", "chromatin lipp", "lipp et al.", "al. 2007 .", "2007 . protein", ". protein phosphatase", "protein phosphatase pp2a", "phosphatase pp2a acts", "pp2a acts independently", "acts independently of", "independently of its", "of its catalytic", "its catalytic activity", "catalytic activity to", "activity to target", "to target condensin", "target condensin ii", "condensin ii complex", "ii complex to", "complex to chromatin", "chromatin but", "but does not", "does not interact", "not interact with", "interact with condensin", "with condensin i", "i takemoto", "2009 . full", ". full activation", "full activation of", "activation of condensin", "condensin i requires", "i requires dephosphorylation", "requires dephosphorylation of", "dephosphorylation of sites", "of sites modified", "sites modified by", "modified by ck2", "by ck2 during", "ck2 during interphase", "interphase takemoto", "al. 2006 .", "2006 . besides", ". besides being", "besides being essential", "being essential for", "essential for chromosome", "for chromosome condensation", "chromosome condensation in", "condensation in mitosis", "mitosis condensin", "condensin i may", "i may also", "may also contribute", "also contribute to", "contribute to cohesin", "to cohesin removal", "cohesin removal from", "removal from chromosome", "from chromosome arms", "chromosome arms in", "arms in prometaphase", "prometaphase but", "but the exact", "the exact mechanism", "exact mechanism is", "mechanism is not", "is not known", "known hirota", "the condensin i complex", "condensin i complex is", "i complex is evolutionarily", "complex is evolutionarily conserved", "is evolutionarily conserved and", "evolutionarily conserved and consists", "conserved and consists of", "and consists of five", "consists of five subunits:", "of five subunits: two", "five subunits: two smc", "two smc structural", "smc structural maintenance", "structural maintenance of chromosomes", "of chromosomes family", "chromosomes family subunits", "family subunits smc2", "subunits smc2 and", "and smc4 and", "smc4 and three", "and three non smc", "three non smc subunits", "smc subunits ncapd2", "ncapd2 ncaph and", "ncaph and ncapg. the", "and ncapg. the stoichiometry", "ncapg. the stoichiometry of", "the stoichiometry of the", "stoichiometry of the complex", "of the complex is", "the complex is 1:1:1:1:1", "is 1:1:1:1:1 hirano", "1:1:1:1:1 hirano and", "hirano and mitchinson 1994", "mitchinson 1994 hirano", "1994 hirano et", "hirano et al. 1997", "al. 1997 kimura", "1997 kimura et", "kimura et al. 2001", "et al. 2001 .", "al. 2001 . smc2", "2001 . smc2 and", ". smc2 and smc4", "smc2 and smc4 subunits", "smc4 subunits shared", "subunits shared between", "shared between condensin i", "between condensin i and", "condensin i and condensin", "i and condensin ii", "condensin ii are", "ii are dna", "are dna dependent atpases", "dependent atpases and", "atpases and condensins", "and condensins are able", "condensins are able to", "are able to introduce", "able to introduce positive", "to introduce positive supercoils", "introduce positive supercoils into", "positive supercoils into dna", "supercoils into dna in", "into dna in an", "dna in an atp", "in an atp dependent", "an atp dependent manner", "dependent manner kimura", "manner kimura and", "kimura and hirano 1997", "and hirano 1997 .", "hirano 1997 .

protein", "1997 .

protein levels", ".

protein levels of", "

protein levels of condensin", "levels of condensin subunits", "of condensin subunits are", "condensin subunits are constant", "subunits are constant during", "are constant during the", "constant during the cell", "during the cell cycle", "cell cycle however", "cycle however condensins", "however condensins are enriched", "condensins are enriched on", "are enriched on mitotic", "enriched on mitotic chromosomes.", "on mitotic chromosomes. four", "mitotic chromosomes. four of", "chromosomes. four of the", "four of the five", "of the five subunits", "five subunits smc4", "ncapd2 ncapg and", "are phosphorylated in both", "phosphorylated in both mitotic", "in both mitotic and", "both mitotic and interphase", "mitotic and interphase hela", "and interphase hela cells", "hela cells but", "cells but on", "but on different sites", "different sites takemoto", "sites takemoto et", "takemoto et al. 2004", "et al. 2004 .", "al. 2004 . cdk1", ". cdk1 cdc2", "cdc2 in complex", "in complex with ccnb", "with ccnb cyclin", "ccnb cyclin b", "cyclin b phosphorylates", "b phosphorylates ncapd2", "phosphorylates ncapd2 ncapg", "ncapg and ncaph in", "and ncaph in mitosis", "in mitosis kimura", "mitosis kimura et", "kimura et al. 1998", "al. 1998 kimura", "1998 kimura et", "al. 2001 takemoto", "2001 takemoto et", "takemoto et al. 2006", "al. 2006 murphy", "2006 murphy et", "murphy et al. 2008", "2008 but", "but other mitotic kinases", "mitotic kinases such", "kinases such as", "as plk1 st", "plk1 st pierre", "st pierre et al.", "pierre et al. 2009", "2009 and", "and other post translational", "other post translational modifications", "translational modifications such", "modifications such as", "as acetylation may", "acetylation may also", "may also be involved", "be involved reviewed", "involved reviewed by", "reviewed by bazile et", "by bazile et al.", "bazile et al. 2010", "et al. 2010 .", "al. 2010 . global", "2010 . global proteomic", ". global proteomic analysis", "global proteomic analysis of", "proteomic analysis of human", "analysis of human cell", "of human cell lines", "human cell lines has", "cell lines has identified", "lines has identified n6", "has identified n6 acetylation", "identified n6 acetylation of", "n6 acetylation of lysine", "acetylation of lysine residues", "of lysine residues in", "lysine residues in condensin", "residues in condensin subunits", "in condensin subunits smc2", "subunits smc2 smc4", "smc2 smc4 and", "and ncaph choudhary", "ncaph choudhary et", "choudhary et al. 2009", "et al. 2009 .", "al. 2009 . another", "2009 . another high", ". another high throughput", "another high throughput proteomic", "high throughput proteomic study", "throughput proteomic study showed", "proteomic study showed that", "study showed that condensin", "showed that condensin i", "that condensin i subunits", "condensin i subunits ncapd2", "i subunits ncapd2 and", "subunits ncapd2 and ncaph", "ncapd2 and ncaph are", "and ncaph are phosphorylated", "ncaph are phosphorylated upon", "are phosphorylated upon dna", "phosphorylated upon dna damage", "dna damage probably", "damage probably by", "probably by atm or", "by atm or atr", "atm or atr kinase", "atr kinase matsuoka", "kinase matsuoka et", "matsuoka et al. 2007", "et al. 2007 .

", "al. 2007 .

as", "2007 .

as condensin", ".

as condensin i", "as condensin i is", "condensin i is cytosolic", "is cytosolic it", "cytosolic it gains", "it gains access to", "gains access to chromosomes", "access to chromosomes only", "to chromosomes only after", "chromosomes only after the", "only after the nuclear", "after the nuclear envelope", "the nuclear envelope breakdown", "nuclear envelope breakdown at", "envelope breakdown at the", "breakdown at the start", "at the start of", "the start of prometaphase", "of prometaphase ono", "prometaphase ono et", "ono et al. 2004", "al. 2004 . condensin", "2004 . condensin i", "condensin i activated", "i activated by", "activated by cdk1 mediated", "by cdk1 mediated phosphorylation", "mediated phosphorylation promotes", "phosphorylation promotes hypercondensation", "promotes hypercondensation of chromosomes", "hypercondensation of chromosomes that", "of chromosomes that were", "chromosomes that were condensed", "that were condensed in", "were condensed in prophase", "condensed in prophase through", "in prophase through the", "prophase through the action", "through the action of", "the action of condensin", "action of condensin ii", "condensin ii hirota", "ii hirota et", "hirota et al. 2004", "al. 2004 . aurkb", "2004 . aurkb may", ". aurkb may also", "aurkb may also regulate", "may also regulate association", "also regulate association of", "regulate association of condensin", "association of condensin i", "of condensin i complex", "condensin i complex with", "i complex with chromatin", "with chromatin lipp", "chromatin lipp et", "lipp et al. 2007", "et al. 2007 .", "al. 2007 . protein", "2007 . protein phosphatase", ". protein phosphatase pp2a", "protein phosphatase pp2a acts", "phosphatase pp2a acts independently", "pp2a acts independently of", "acts independently of its", "independently of its catalytic", "of its catalytic activity", "its catalytic activity to", "catalytic activity to target", "activity to target condensin", "to target condensin ii", "target condensin ii complex", "condensin ii complex to", "ii complex to chromatin", "to chromatin but", "chromatin but does", "but does not interact", "does not interact with", "not interact with condensin", "interact with condensin i", "condensin i takemoto", "i takemoto et", "takemoto et al. 2009", "al. 2009 . full", "2009 . full activation", ". full activation of", "full activation of condensin", "activation of condensin i", "of condensin i requires", "condensin i requires dephosphorylation", "i requires dephosphorylation of", "requires dephosphorylation of sites", "dephosphorylation of sites modified", "of sites modified by", "sites modified by ck2", "modified by ck2 during", "by ck2 during interphase", "during interphase takemoto", "interphase takemoto et", "et al. 2006 .", "al. 2006 . besides", "2006 . besides being", ". besides being essential", "besides being essential for", "being essential for chromosome", "essential for chromosome condensation", "for chromosome condensation in", "chromosome condensation in mitosis", "in mitosis condensin", "mitosis condensin i", "condensin i may also", "i may also contribute", "may also contribute to", "also contribute to cohesin", "contribute to cohesin removal", "to cohesin removal from", "cohesin removal from chromosome", "removal from chromosome arms", "from chromosome arms in", "chromosome arms in prometaphase", "in prometaphase but", "prometaphase but the", "but the exact mechanism", "the exact mechanism is", "exact mechanism is not", "mechanism is not known", "not known hirota", "known hirota et", "the condensin i complex is", "condensin i complex is evolutionarily", "i complex is evolutionarily conserved", "complex is evolutionarily conserved and", "is evolutionarily conserved and consists", "evolutionarily conserved and consists of", "conserved and consists of five", "and consists of five subunits:", "consists of five subunits: two", "of five subunits: two smc", "subunits: two smc structural", "two smc structural maintenance", "smc structural maintenance of", "maintenance of chromosomes family", "of chromosomes family subunits", "family subunits smc2 and", "subunits smc2 and smc4", "smc2 and smc4 and", "and smc4 and three", "smc4 and three non", "and three non smc subunits", "non smc subunits ncapd2", "subunits ncapd2 ncaph", "ncapd2 ncaph and ncapg.", "ncaph and ncapg. the stoichiometry", "and ncapg. the stoichiometry of", "ncapg. the stoichiometry of the", "the stoichiometry of the complex", "stoichiometry of the complex is", "of the complex is 1:1:1:1:1", "complex is 1:1:1:1:1 hirano", "is 1:1:1:1:1 hirano and", "1:1:1:1:1 hirano and mitchinson", "and mitchinson 1994 hirano", "mitchinson 1994 hirano et", "1994 hirano et al.", "et al. 1997 kimura", "al. 1997 kimura et", "1997 kimura et al.", "kimura et al. 2001 .", "et al. 2001 . smc2", "al. 2001 . smc2 and", "2001 . smc2 and smc4", ". smc2 and smc4 subunits", "and smc4 subunits shared", "smc4 subunits shared between", "subunits shared between condensin", "shared between condensin i and", "between condensin i and condensin", "condensin i and condensin ii", "and condensin ii are", "condensin ii are dna", "ii are dna dependent", "dna dependent atpases and", "dependent atpases and condensins", "atpases and condensins are", "and condensins are able to", "condensins are able to introduce", "are able to introduce positive", "able to introduce positive supercoils", "to introduce positive supercoils into", "introduce positive supercoils into dna", "positive supercoils into dna in", "supercoils into dna in an", "into dna in an atp", "dna in an atp dependent", "in an atp dependent manner", "atp dependent manner kimura", "dependent manner kimura and", "manner kimura and hirano", "kimura and hirano 1997 .", "and hirano 1997 .

protein", "hirano 1997 .

protein levels", "1997 .

protein levels of", ".

protein levels of condensin", "

protein levels of condensin subunits", "levels of condensin subunits are", "of condensin subunits are constant", "condensin subunits are constant during", "subunits are constant during the", "are constant during the cell", "constant during the cell cycle", "the cell cycle however", "cell cycle however condensins", "cycle however condensins are", "however condensins are enriched on", "condensins are enriched on mitotic", "are enriched on mitotic chromosomes.", "enriched on mitotic chromosomes. four", "on mitotic chromosomes. four of", "mitotic chromosomes. four of the", "chromosomes. four of the five", "four of the five subunits", "the five subunits smc4", "subunits smc4 ncapd2", "smc4 ncapd2 ncapg", "ncapd2 ncapg and ncaph", "ncapg and ncaph are", "ncaph are phosphorylated in", "are phosphorylated in both mitotic", "phosphorylated in both mitotic and", "in both mitotic and interphase", "both mitotic and interphase hela", "mitotic and interphase hela cells", "interphase hela cells but", "hela cells but on", "cells but on different", "on different sites takemoto", "different sites takemoto et", "sites takemoto et al.", "takemoto et al. 2004 .", "et al. 2004 . cdk1", "2004 . cdk1 cdc2", "cdk1 cdc2 in", "cdc2 in complex with", "complex with ccnb cyclin", "with ccnb cyclin b", "cyclin b phosphorylates ncapd2", "phosphorylates ncapd2 ncapg and", "ncapg and ncaph in mitosis", "ncaph in mitosis kimura", "in mitosis kimura et", "mitosis kimura et al.", "et al. 1998 kimura", "al. 1998 kimura et", "1998 kimura et al.", "et al. 2001 takemoto", "al. 2001 takemoto et", "2001 takemoto et al.", "et al. 2006 murphy", "al. 2006 murphy et", "2006 murphy et al.", "al. 2008 but", "2008 but other", "other mitotic kinases such", "mitotic kinases such as", "kinases such as plk1", "such as plk1 st", "as plk1 st pierre", "plk1 st pierre et", "st pierre et al. 2009", "al. 2009 and", "2009 and other", "and other post translational modifications", "post translational modifications such", "translational modifications such as", "modifications such as acetylation", "such as acetylation may", "as acetylation may also", "acetylation may also be", "also be involved reviewed", "be involved reviewed by", "involved reviewed by bazile", "reviewed by bazile et al.", "by bazile et al. 2010", "bazile et al. 2010 .", "et al. 2010 . global", "al. 2010 . global proteomic", "2010 . global proteomic analysis", ". global proteomic analysis of", "global proteomic analysis of human", "proteomic analysis of human cell", "analysis of human cell lines", "of human cell lines has", "human cell lines has identified", "cell lines has identified n6", "lines has identified n6 acetylation", "has identified n6 acetylation of", "identified n6 acetylation of lysine", "n6 acetylation of lysine residues", "acetylation of lysine residues in", "of lysine residues in condensin", "lysine residues in condensin subunits", "residues in condensin subunits smc2", "condensin subunits smc2 smc4", "subunits smc2 smc4 and", "smc2 smc4 and ncaph", "smc4 and ncaph choudhary", "and ncaph choudhary et", "ncaph choudhary et al.", "choudhary et al. 2009 .", "et al. 2009 . another", "al. 2009 . another high", "2009 . another high throughput", ". another high throughput proteomic", "another high throughput proteomic study", "high throughput proteomic study showed", "throughput proteomic study showed that", "proteomic study showed that condensin", "study showed that condensin i", "showed that condensin i subunits", "that condensin i subunits ncapd2", "condensin i subunits ncapd2 and", "i subunits ncapd2 and ncaph", "subunits ncapd2 and ncaph are", "ncapd2 and ncaph are phosphorylated", "and ncaph are phosphorylated upon", "ncaph are phosphorylated upon dna", "are phosphorylated upon dna damage", "upon dna damage probably", "dna damage probably by", "damage probably by atm", "probably by atm or atr", "by atm or atr kinase", "or atr kinase matsuoka", "atr kinase matsuoka et", "kinase matsuoka et al.", "matsuoka et al. 2007 .

", "et al. 2007 .

as", "al. 2007 .

as condensin", "2007 .

as condensin i", ".

as condensin i is", "as condensin i is cytosolic", "i is cytosolic it", "is cytosolic it gains", "cytosolic it gains access", "it gains access to chromosomes", "gains access to chromosomes only", "access to chromosomes only after", "to chromosomes only after the", "chromosomes only after the nuclear", "only after the nuclear envelope", "after the nuclear envelope breakdown", "the nuclear envelope breakdown at", "nuclear envelope breakdown at the", "envelope breakdown at the start", "breakdown at the start of", "at the start of prometaphase", "start of prometaphase ono", "of prometaphase ono et", "prometaphase ono et al.", "ono et al. 2004 .", "et al. 2004 . condensin", "al. 2004 . condensin i", ". condensin i activated", "condensin i activated by", "i activated by cdk1", "activated by cdk1 mediated phosphorylation", "cdk1 mediated phosphorylation promotes", "mediated phosphorylation promotes hypercondensation", "phosphorylation promotes hypercondensation of", "promotes hypercondensation of chromosomes that", "hypercondensation of chromosomes that were", "of chromosomes that were condensed", "chromosomes that were condensed in", "that were condensed in prophase", "were condensed in prophase through", "condensed in prophase through the", "in prophase through the action", "prophase through the action of", "through the action of condensin", "the action of condensin ii", "of condensin ii hirota", "condensin ii hirota et", "ii hirota et al.", "hirota et al. 2004 .", "et al. 2004 . aurkb", "al. 2004 . aurkb may", "2004 . aurkb may also", ". aurkb may also regulate", "aurkb may also regulate association", "may also regulate association of", "also regulate association of condensin", "regulate association of condensin i", "association of condensin i complex", "of condensin i complex with", "condensin i complex with chromatin", "complex with chromatin lipp", "with chromatin lipp et", "chromatin lipp et al.", "lipp et al. 2007 .", "et al. 2007 . protein", "al. 2007 . protein phosphatase", "2007 . protein phosphatase pp2a", ". protein phosphatase pp2a acts", "protein phosphatase pp2a acts independently", "phosphatase pp2a acts independently of", "pp2a acts independently of its", "acts independently of its catalytic", "independently of its catalytic activity", "of its catalytic activity to", "its catalytic activity to target", "catalytic activity to target condensin", "activity to target condensin ii", "to target condensin ii complex", "target condensin ii complex to", "condensin ii complex to chromatin", "complex to chromatin but", "to chromatin but does", "chromatin but does not", "but does not interact with", "does not interact with condensin", "not interact with condensin i", "with condensin i takemoto", "condensin i takemoto et", "i takemoto et al.", "takemoto et al. 2009 .", "et al. 2009 . full", "al. 2009 . full activation", "2009 . full activation of", ". full activation of condensin", "full activation of condensin i", "activation of condensin i requires", "of condensin i requires dephosphorylation", "condensin i requires dephosphorylation of", "i requires dephosphorylation of sites", "requires dephosphorylation of sites modified", "dephosphorylation of sites modified by", "of sites modified by ck2", "sites modified by ck2 during", "modified by ck2 during interphase", "ck2 during interphase takemoto", "during interphase takemoto et", "interphase takemoto et al.", "takemoto et al. 2006 .", "et al. 2006 . besides", "al. 2006 . besides being", "2006 . besides being essential", ". besides being essential for", "besides being essential for chromosome", "being essential for chromosome condensation", "essential for chromosome condensation in", "for chromosome condensation in mitosis", "condensation in mitosis condensin", "in mitosis condensin i", "mitosis condensin i may", "condensin i may also contribute", "i may also contribute to", "may also contribute to cohesin", "also contribute to cohesin removal", "contribute to 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in", "al. 2009.

in mitotic", "2009.

in mitotic prophase", "prophase chromatin", "chromatin detaches from", "detaches from the", "from the nuclear", "envelope and", "and this contributes", "this contributes to", "contributes to the", "to the nuclear", "nuclear envelope breakdown.", "envelope breakdown. vrk1", "vrk1 and", "and possibly vrk2", "vrk2 mediated", "mediated phosphorylation of", "phosphorylation of banf1", "banf1 baf", "a protein that", "protein that simultaneously", "that simultaneously interacts", "simultaneously interacts with", "interacts with dna", "dna lem", "lem domain inner", "domain inner nuclear", "inner nuclear membrane", "nuclear membrane proteins", "proteins and", "lamins zheng", "zheng et al.", "et al. 2000", "2000 shumaker", "shumaker et al.", "et al. 2001", "2001 haraguchi", "haraguchi et al.", "2001 mansharamani", "mansharamani and wilson", "and wilson 2005", "2005 brachner", "brachner et al.", "et al. 2005", "2005 is", "is considered to", "considered to be", "to be one", "be one of", "one of the", "of the key", "the key steps", "key steps in", "steps in the", "in the detachment", "the detachment of", "detachment of the", "envelope from chromatin", "chromatin bengtsson", "bengtsson and wilson", "and wilson 2006", "2006 nichols", "nichols et al.", "et al. 2006", "2006 gorjanacz", "gorjanacz et al.", "et al. 2007", "al. 2007 .", "the nuclear envelope breakdown", "envelope breakdown nebd", "nebd happens in", "happens in late prophase", "in late prophase of", "late prophase of mitosis", "prophase of mitosis and", "of mitosis and involves", "mitosis and involves disassembly", "and involves disassembly of", "involves disassembly of the", "disassembly of the nuclear", "of the nuclear pore", "the nuclear pore complex", "pore complex depolymerization", "complex depolymerization of", "depolymerization of the nuclear", "of the nuclear lamina", "nuclear lamina and", "lamina and clearance", "and clearance of nuclear", "clearance of nuclear envelope", "of nuclear envelope from", "nuclear envelope from chromatin.", "envelope from chromatin. nebd", "from chromatin. nebd allows", "chromatin. nebd allows mitotic", "nebd allows mitotic spindle", "allows mitotic spindle microtubules", "mitotic spindle microtubules to", "spindle microtubules to access", "microtubules to access condensed", "to access condensed chromosomes", "access condensed chromosomes at", "condensed chromosomes at kinetochores", "chromosomes at kinetochores and", "at kinetochores and enables", "kinetochores and enables nuclear", "and enables nuclear division", "enables nuclear division and", "nuclear division and segregation", "division and segregation of", "and segregation of genetic", "segregation of genetic material", "of genetic material to", "genetic material to two", "material to two daughter", "to two daughter cells.", "two daughter cells. for", "daughter cells. for a", "cells. for a recent", "for a recent review", "recent review please", "review please refer", "please refer to guttinger", "refer to guttinger et", "to guttinger et al.", "guttinger et al. 2009.

in", "et al. 2009.

in mitotic", "al. 2009.

in mitotic prophase", "mitotic prophase chromatin", "prophase chromatin detaches", "chromatin detaches from the", "detaches from the nuclear", "from the nuclear envelope", "nuclear envelope and", "envelope and this", "and this contributes to", "this contributes to the", "contributes to the nuclear", "to the nuclear envelope", "the nuclear envelope breakdown.", "nuclear envelope breakdown. vrk1", "breakdown. vrk1 and", "vrk1 and possibly", "possibly vrk2 mediated", "vrk2 mediated phosphorylation", "mediated phosphorylation of banf1", "of banf1 baf", "baf a", "a protein that simultaneously", "protein that simultaneously interacts", "that simultaneously interacts with", "simultaneously interacts with dna", "with dna lem", "dna lem domain", "lem domain inner nuclear", "domain inner nuclear membrane", "inner nuclear membrane proteins", "membrane proteins and", "proteins and lamins", "and lamins zheng", "lamins zheng et", "zheng et al. 2000", "al. 2000 shumaker", "2000 shumaker et", "shumaker et al. 2001", "al. 2001 haraguchi", "2001 haraguchi et", "haraguchi et al. 2001", "al. 2001 mansharamani", "2001 mansharamani and", "mansharamani and wilson 2005", "wilson 2005 brachner", "2005 brachner et", "brachner et al. 2005", "al. 2005 is", "2005 is considered", "is considered to be", "considered to be one", "to be one of", "be one of the", "one of the key", "of the key steps", "the key steps in", "key steps in the", "steps in the detachment", "in the detachment of", "the detachment of the", "detachment of the nuclear", "of the nuclear envelope", "the nuclear envelope from", "nuclear envelope from chromatin", "from chromatin bengtsson", "chromatin bengtsson and", "bengtsson and wilson 2006", "wilson 2006 nichols", "2006 nichols et", "nichols et al. 2006", "al. 2006 gorjanacz", "2006 gorjanacz et", "gorjanacz et al. 2007", "et al. 2007 .", "nuclear envelope breakdown nebd", "breakdown nebd happens", "nebd happens in late", "happens in late prophase of", "in late prophase of mitosis", "late prophase of mitosis and", "prophase of mitosis and involves", "of mitosis and involves disassembly", "mitosis and involves disassembly of", "and involves disassembly of the", "involves disassembly of the nuclear", "disassembly of the nuclear pore", "of the nuclear pore complex", "nuclear pore complex depolymerization", "pore complex depolymerization of", "complex depolymerization of the", "depolymerization of the nuclear lamina", "the nuclear lamina and", "nuclear lamina and clearance", "lamina and clearance of", "and clearance of nuclear envelope", "clearance of nuclear envelope from", "of nuclear envelope from chromatin.", "nuclear envelope from chromatin. nebd", "envelope from chromatin. nebd allows", "from chromatin. nebd allows mitotic", "chromatin. nebd allows mitotic spindle", "nebd allows mitotic spindle microtubules", "allows mitotic spindle microtubules to", "mitotic spindle microtubules to access", "spindle microtubules to access condensed", "microtubules to access condensed chromosomes", "to access condensed chromosomes at", "access condensed chromosomes at kinetochores", "condensed chromosomes at kinetochores and", "chromosomes at kinetochores and enables", "at kinetochores and enables nuclear", "kinetochores and enables nuclear division", "and enables nuclear division and", "enables nuclear division and segregation", "nuclear division and segregation of", "division and segregation of genetic", "and segregation of genetic material", "segregation of genetic material to", "of genetic material to two", "genetic material to two daughter", "material to two daughter cells.", "to two daughter cells. for", "two daughter cells. for a", "daughter cells. for a recent", "cells. for a recent review", "a recent review please", "recent review please refer", "review please refer to", "please refer to guttinger et", "refer to guttinger et al.", "to guttinger et al. 2009.

in", "guttinger et al. 2009.

in mitotic", "et al. 2009.

in mitotic prophase", "2009.

in mitotic prophase chromatin", "mitotic prophase chromatin detaches", "prophase chromatin detaches from", "chromatin detaches from the nuclear", "detaches from the nuclear envelope", "the nuclear envelope and", "nuclear envelope and this", "envelope and this contributes", "and this contributes to the", "this contributes to the nuclear", "contributes to the nuclear envelope", "to the nuclear envelope breakdown.", "the nuclear envelope breakdown. vrk1", "envelope breakdown. vrk1 and", "breakdown. vrk1 and possibly", "vrk1 and possibly vrk2", "and possibly vrk2 mediated", "possibly vrk2 mediated phosphorylation", "vrk2 mediated phosphorylation of", "phosphorylation of banf1 baf", "baf a protein", "a protein that simultaneously interacts", "protein that simultaneously interacts with", "that simultaneously interacts with dna", "interacts with dna lem", "with dna lem domain", "dna lem domain inner", "lem domain inner nuclear membrane", "domain inner nuclear membrane proteins", "nuclear 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2006 nichols", "wilson 2006 nichols et", "2006 nichols et al.", "et al. 2006 gorjanacz", "al. 2006 gorjanacz et", "2006 gorjanacz et al.", "gorjanacz et al. 2007 ." ] }, { "record_id": "GLY_000594_1_911", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2980767", "r hsa", "hsa 2980767", "r hsa 2980767" ] }, { "record_id": "GLY_000594_1_911", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activation of", "of nima", "nima kinases", "kinases nek9", "activation of nima", "of nima kinases", "nima kinases nek9", "nek9 nek6", "nek6 nek7", "activation of nima kinases", "of nima kinases nek9", "kinases nek9 nek6", "activation of nima kinases nek9", "nima kinases nek9 nek6", "nek9 nek6 nek7", "nek6 and", "and nek7", "nek7 are", "are activated", "activated during", "during mitosis", "mitosis by", "by another", "another nima", "nima family", "family kinase", "belham et", "et al.", "al. 2003", "richards 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concentration", "concentration .", ". in", "in humans", "there are", "are 28", "28 trp", "trp genes", "genes arranged", "arranged into", "into 6", "6 subfamilies", "and trpv", "wu et", "et al.", "al. 2010", "2010 .", ". each", "each trp", "trp channel", "channel subunit", "subunit consists", "consists of", "of six", "six putative", "putative transmembrane", "transmembrane spanning", "spanning segments", "s1 s6", "with a", "a pore", "pore forming", "forming loop", "loop between", "between s5", "s5 and", "and s6.", "s6. these", "these subunits", "subunits assemble", "assemble into", "into tetramers", "tetramers to", "to form", "form functional", "functional channels.", "channels. all", "all functionally", "functionally characterized", "characterized trp", "channels are", "are permeable", "permeable to", "to ca2+", "ca2+ except", "except trmp4", "trmp4 and", "and 5", "5 which", "which are", "are only", "only permeable", "to monovalent", "monovalent cations", "cations such", "as na+", "latorre et", "al. 2009", "2009 .", ". most", "most trps", "trps can", "can cause", "cause channelopathies", "channelopathies which", "are risk", "risk factors", "factors for", "for many", "many disease", "disease states", "nilius &", "& owsianik", "owsianik 2010", "transient receptor potential", "potential trp", "channel proteins were", "proteins were first", "were first discovered", "first discovered in", "discovered in drosophila", "in drosophila melanogaster", "drosophila melanogaster and", "melanogaster and have", "and have many", "have many homologues", "many homologues in", "homologues in other", "in other species", "other species including", "species including humans.", "including humans. trps", "trps form", "form cationic channels", "cationic channels that", "channels that can", "that can detect", "can detect sensory", "detect sensory stimuli", "sensory stimuli such", "stimuli such as", "such as temperature", "temperature ph", "ph or oxidative", "or oxidative stress", 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temperature ph or", "temperature ph or oxidative", "ph or oxidative stress and", "or oxidative stress and transduce", "oxidative stress and transduce that", "stress and transduce that into", "and transduce that into either", "transduce that into either electrical", "into either electrical change", "either electrical change in", "electrical change in membrane", "in membrane potential or", "membrane potential or chemical", "potential or chemical signals", "or chemical signals change", "chemical signals change in", "signals change in intracellular", "change in intracellular ca2+ concentration", "in intracellular ca2+ concentration .", "intracellular ca2+ concentration . in", "ca2+ concentration . in humans", ". in humans there", "in humans there are", "humans there are 28", "there are 28 trp genes", "are 28 trp genes arranged", "28 trp genes arranged into", "trp genes arranged into 6", "genes arranged into 6 subfamilies", "into 6 subfamilies trpa", "subfamilies trpa trpc", "trpa trpc trpm", "trpc trpm trpml", "trpm trpml trpp", "trpml trpp and", "and trpv wu et", "trpv wu et al.", "wu et al. 2010 .", "et al. 2010 . each", "al. 2010 . each trp", "2010 . each trp channel", ". each trp channel subunit", "each trp channel subunit consists", "trp channel subunit consists of", "channel subunit consists of six", "subunit consists of six putative", "consists of six putative transmembrane", "of six putative transmembrane spanning", "six putative transmembrane spanning segments", "transmembrane spanning segments s1", "spanning segments s1 s6", "s1 s6 with a", "s6 with a pore", "with a pore forming loop", "a pore forming loop between", "pore forming loop between s5", "forming loop between s5 and", "loop between s5 and s6.", "between s5 and s6. these", "s5 and s6. these subunits", "and s6. these subunits assemble", "s6. these subunits assemble into", "these subunits assemble into tetramers", "subunits assemble into tetramers to", "assemble into tetramers to form", "into tetramers to form functional", "tetramers to form functional channels.", "to form functional channels. all", "form functional channels. all functionally", "functional channels. all functionally characterized", "channels. all functionally characterized trp", "all functionally characterized trp channels", "functionally characterized trp channels are", "characterized trp channels are permeable", "trp channels are permeable to", "channels are permeable to ca2+", "are permeable to ca2+ except", "permeable to ca2+ except trmp4", "to ca2+ except trmp4 and", "ca2+ except trmp4 and 5", "except trmp4 and 5 which", "trmp4 and 5 which are", "and 5 which are only", "5 which are only permeable", "which are only permeable to", "are only permeable to monovalent", "only permeable to monovalent cations", "permeable to monovalent cations such", "to monovalent cations such as", "monovalent cations such as na+", "such as na+ latorre", "as na+ latorre et", "na+ latorre et al.", "latorre et al. 2009 .", "et al. 2009 . most", "al. 2009 . most trps", "2009 . most trps can", ". most trps can cause", "most trps can cause channelopathies", "trps can cause channelopathies which", "can cause channelopathies which are", "cause channelopathies which are risk", "channelopathies which are risk factors", "which are risk factors for", "are risk factors for many", "risk factors for many disease", "factors for many disease states", "many disease states nilius", "disease states nilius &", "states nilius & owsianik", "nilius & owsianik 2010 ." ] }, { "record_id": "GLY_000594_1_917", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3304356", "r hsa", "hsa 3304356", "r hsa 3304356" ] }, { "record_id": "GLY_000594_1_917", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "smad2/3 phosphorylation", "phosphorylation motif", "motif mutants", "mutants in", "in cancer", "smad2/3 phosphorylation motif", "phosphorylation motif 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"1996 nakao et al.", "nakao et al. 1997 .", "et al. 1997 . once", "al. 1997 . once phosphorylated", ". once phosphorylated smad2", "once phosphorylated smad2 and", "phosphorylated smad2 and smad3", "smad2 and smad3 form transcriptionally", "and smad3 form transcriptionally active", "smad3 form transcriptionally active heterotrimers", "form transcriptionally active heterotrimers with", "transcriptionally active heterotrimers with smad4", "heterotrimers with smad4 chacko", "with smad4 chacko et", "smad4 chacko et al.", "et al. 2001 chacko", "al. 2001 chacko et", "2001 chacko et al.", "chacko et al. 2004 .", "et al. 2004 . phosphorylation", "al. 2004 . phosphorylation motif", "2004 . phosphorylation motif mutants", ". phosphorylation motif mutants of", "phosphorylation motif mutants of smad2", "motif mutants of smad2 and", "mutants of smad2 and smad3", "of smad2 and smad3 cannot", "smad2 and smad3 cannot be", "and smad3 cannot be activated", "smad3 cannot be activated by", "cannot be 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is deleted from the", "is deleted from the protein", "deleted from the protein sequence", "from the protein sequence or", "the protein sequence or truncated", "sequence or truncated fleming", "or truncated fleming et", "truncated fleming et al.", "fleming et al. 2013 ." ] }, { "record_id": "GLY_000594_1_918", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3359462", "r hsa", "hsa 3359462", "r hsa 3359462" ] }, { "record_id": "GLY_000594_1_918", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective amn", "amn causes", "causes mga1", "defective amn causes", "amn causes mga1", "defective amn causes mga1", "defects in", "in amn", "amn cause", "cause recessive", "recessive hereditary", "hereditary megaloblastic", "megaloblastic anemia", "anemia 1", "rh mga1", "mga1 aka", "aka mga1", "mga1 norwegian", "norwegian type", "type or", "or imerslund", "imerslund grasbeck", "grasbeck syndrome", "i gs", 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hsf1 is", "sistonen 2011 .

hsf1 is constitutively", "2011 .

hsf1 is constitutively present", ".

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activation", "

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activation", ".

activation of", "

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"phosphorylation of hsf1", "hsf1 cotto", "1996 kline", "kline mp &", "mp & morimoto", "& morimoto ri", "morimoto ri 1997", "ri 1997 .", "1997 . while", ". while there", "while there is", "there is a", "is a sufficient", "a sufficient evidence", "sufficient evidence to", "evidence to suggest", "to suggest that", "suggest that phosphorylation", "that phosphorylation of", "of hsf1 is", "hsf1 is essential", "is essential to", "essential to modulate", "to modulate hsf1", "modulate hsf1 transactiviting", "hsf1 transactiviting capacity", "capacity mechanisms", "mechanisms behind stress", "behind stress stimuli", "stress stimuli and", "stimuli and kinases/phosphatases", "and kinases/phosphatases involved", "kinases/phosphatases involved have", "involved have not", "have not been", "not been clearly", "been clearly established.", "acquisition of dna binding", "of dna binding activity", "dna binding activity by", "binding activity by hsf1", "activity by hsf1 is", "by hsf1 is necessary", "hsf1 is necessary but", "is necessary but insufficient", "necessary but insufficient for", "but insufficient for transcriptional", "insufficient for transcriptional activation", "transcriptional activation cotto", "activation cotto jj", "cotto jj et al.", "jj et al. 1996", "al. 1996 trinklein", "1996 trinklein nd", "trinklein nd et al.", "nd et al. 2004", "et al. 2004 .", "al. 2004 . in", "2004 . in addition", ". in addition to", "in addition to having", "addition to having a", "to having a sequence", "having a sequence specific", "a sequence specific dna", "sequence specific dna binding", "specific dna binding domain", "binding domain hsf1", "domain hsf1 contains", "hsf1 contains a c", "contains a c terminal", "a c terminal region", "c terminal region which", "terminal region which is", "region which is involved", "which is involved in", "is involved in activating", "involved in activating the", "in activating the transcription", "activating the transcription of", "the transcription of the", "transcription of the target", "of the target genes", "target genes green", "genes green m", "green m et al.", "m et al. 1995", "et al. 1995 .", "al. 1995 . however", ". however the", "however the transactivating", "the transactivating ability of", "transactivating ability of the", "ability of the transactivation", "of the transactivation domain", "the transactivation domain itself", "transactivation domain itself is", "domain itself is not", "itself is not stress", "is not stress sensitive.", "not stress sensitive. rather", "sensitive. rather it's", "rather it's controled", "it's controled by a", "controled by a regulatory", "by a regulatory domain", "a regulatory domain of", "regulatory domain of hsf1", "of hsf1 amino", "hsf1 amino acids", "amino acids 221 310", "310 which", "which represses the transactivating", "represses the transactivating ability", "the transactivating ability under", "transactivating ability under normal", "ability under normal physiological", "normal physiological conditions", "conditions green m", "al. 1995 zuo", "1995 zuo j", "zuo j et al.", "j et al. 1995", "al. 1995 newton", "1995 newton em", "newton em et al.", "em et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the hsf1", ". the hsf1 transactivation", "the hsf1 transactivation domain", "hsf1 transactivation domain can", "transactivation domain can be", "domain can be divided", "can be divided into", "be divided into two", "divided into two distinct", "into two distinct regions", "distinct regions activation", "regions activation domain", "domain 1 ad1", "ad1 and activation", "and activation domain 2", "domain 2 ad2", "ad2 brown", "brown sa et al.", "sa et al. 1998", "et al. 1998 .", "al. 1998 . ad1", "1998 . ad1 and", ". ad1 and ad2", "ad1 and ad2 each", "and ad2 each contain", "ad2 each contain residues", "each contain residues that", "contain residues that are", "residues that are important", "that are important for", "are important for both", "important for both transcriptional", "for both transcriptional initiation", "both transcriptional initiation and", "transcriptional initiation and elongation.", "initiation and elongation. mutations", "and elongation. mutations in", "elongation. mutations in acidic", "mutations in acidic residues", "in acidic residues in", "acidic residues in both", "residues in both ad1", "in both ad1 and", "both ad1 and ad2", "ad1 and ad2 preferentially", "and ad2 preferentially affect", "ad2 preferentially affect the", "preferentially affect the ability", "affect the ability of", "the ability of hsf1", "ability of hsf1 to", "of hsf1 to stimulate", "hsf1 to stimulate transcriptional", "to stimulate transcriptional initiation", "transcriptional initiation while", "initiation while mutations", "while mutations in phenylalanine", "mutations in phenylalanine residues", "in phenylalanine residues preferentially", "phenylalanine residues preferentially affect", "residues preferentially affect stimulation", "preferentially affect stimulation of", "affect stimulation of elongation", "of elongation brown", "elongation brown sa", "al. 1998 .

activation", "1998 .

activation of", ".

activation of the", "

activation of the dna", "of the dna bound", "the dna bound but", "dna bound but transcriptionally", "bound but transcriptionally incompetent", "but transcriptionally incompetent hsf1", "transcriptionally incompetent hsf1 is", "incompetent hsf1 is thought", "hsf1 is thought to", "is thought to occur", "thought to occur upon", "to occur upon stress", "occur upon stress induced", "upon stress induced hsf1", "stress induced hsf1 phosphorylation", "induced hsf1 phosphorylation at", "hsf1 phosphorylation at several", "phosphorylation at several serine", "at several serine residues", "serine residues ding", "residues ding xz", "ding xz et al.", "xz et al. 1997", "al. 1997 holmberg", "1997 holmberg ci", "holmberg ci et al.", "ci et al. 2001", "al. 2001 guettouche", "2001 guettouche t", "guettouche t et al.", "t et al. 2005", "et al. 2005 .", "al. 2005 . in", "2005 . in cells", ". in cells exposed", "in cells exposed to", "cells exposed to heat", "to heat acquisition", "heat acquisition of", "acquisition of hse dna", "of hse dna binding", "hse dna binding activity", "dna binding activity was", "binding activity was observed", "activity was observed to", "was observed to precede", "observed to precede phosphorylation", "to precede phosphorylation of", "precede phosphorylation of hsf1", "of hsf1 cotto", "hsf1 cotto jj", "al. 1996 kline", "1996 kline mp", "kline mp & morimoto", "mp & morimoto ri", "& morimoto ri 1997", "morimoto ri 1997 .", "ri 1997 . while", "1997 . while there", ". while there is", "while there is a", "there is a sufficient", "is a sufficient evidence", "a sufficient evidence to", "sufficient evidence to suggest", "evidence to suggest that", "to suggest that phosphorylation", "suggest that phosphorylation of", "that phosphorylation of hsf1", "phosphorylation of hsf1 is", "of hsf1 is essential", "hsf1 is essential to", "is essential to modulate", "essential to modulate hsf1", "to modulate hsf1 transactiviting", "modulate hsf1 transactiviting capacity", "transactiviting capacity mechanisms", "capacity mechanisms behind", "mechanisms behind stress stimuli", "behind stress stimuli and", "stress stimuli and kinases/phosphatases", "stimuli and kinases/phosphatases involved", "and kinases/phosphatases involved have", "kinases/phosphatases involved have not", "involved have not been", "have not been clearly", "not been clearly established.", "acquisition of dna binding activity", "of dna binding activity by", "dna binding activity by hsf1", "binding activity by hsf1 is", "activity by hsf1 is necessary", "by hsf1 is necessary but", "hsf1 is necessary but insufficient", "is necessary but insufficient for", "necessary but insufficient for transcriptional", "but insufficient for transcriptional activation", "for transcriptional activation cotto", "transcriptional activation cotto jj", "activation cotto jj et", "cotto jj et al. 1996", "et al. 1996 trinklein", "al. 1996 trinklein nd", "1996 trinklein nd et", "trinklein nd et al. 2004", "nd et al. 2004 .", "et al. 2004 . in", "al. 2004 . in addition", "2004 . in addition to", ". in addition to having", "in addition to having a", "addition to having a sequence", "to having a sequence specific", "having a sequence specific dna", "a sequence specific dna binding", "sequence specific dna binding domain", "dna binding domain hsf1", "binding domain hsf1 contains", "domain hsf1 contains a", "hsf1 contains a c terminal", "contains a c terminal region", "a c terminal region which", "c terminal region which is", "terminal region which is involved", "region which is involved in", "which is involved in activating", "is involved in activating the", "involved in activating the transcription", "in activating the transcription of", "activating the transcription of the", "the transcription of the target", "transcription of the target genes", "the target genes green", "target genes green m", "genes green m et", "green m et al. 1995", "m et al. 1995 .", "et al. 1995 . however", "1995 . however the", ". however the transactivating", "however the transactivating ability", "the transactivating ability of the", "transactivating ability of the transactivation", "ability of the transactivation domain", "of the transactivation domain itself", "the transactivation domain itself is", "transactivation domain itself is not", "domain itself is not stress", "itself is not stress sensitive.", "is not stress sensitive. rather", "stress sensitive. rather it's", "sensitive. rather it's controled", "rather it's controled by", "it's controled by a regulatory", "controled by a regulatory domain", "by a regulatory domain of", "a regulatory domain of hsf1", "domain of hsf1 amino", "of hsf1 amino acids", "hsf1 amino acids 221", "221 310 which", "310 which represses", "which represses the transactivating ability", "represses the transactivating ability under", "the transactivating ability under normal", "transactivating ability under normal physiological", "under normal physiological conditions", "physiological conditions green", "conditions green m et", "et al. 1995 zuo", "al. 1995 zuo j", "1995 zuo j et", "zuo j et al. 1995", "et al. 1995 newton", "al. 1995 newton em", "1995 newton em et", "newton em et al. 1996", "em et al. 1996 .", "et al. 1996 . the", "al. 1996 . the hsf1", "1996 . the hsf1 transactivation", ". the hsf1 transactivation domain", "the hsf1 transactivation domain can", "hsf1 transactivation domain can be", "transactivation domain can be divided", "domain can be divided into", "can be divided into two", "be divided into two distinct", "divided into two distinct regions", "two distinct regions activation", "distinct regions activation domain", "regions activation domain 1", "activation domain 1 ad1", "1 ad1 and", "ad1 and activation domain", "activation domain 2 ad2", "ad2 brown sa", "brown sa et al. 1998", "sa et al. 1998 .", "et al. 1998 . ad1", "al. 1998 . ad1 and", "1998 . ad1 and ad2", ". ad1 and ad2 each", "ad1 and ad2 each contain", "and ad2 each contain residues", "ad2 each contain residues that", "each contain residues that are", "contain residues that are important", "residues that are important for", "that are important for both", "are important for both transcriptional", "important for both transcriptional initiation", "for both transcriptional initiation and", "both transcriptional initiation and elongation.", "transcriptional initiation and elongation. mutations", "initiation and elongation. mutations in", "and elongation. mutations in acidic", "elongation. mutations in acidic residues", "mutations in acidic residues in", "in acidic residues in both", "acidic residues in both ad1", "residues in both ad1 and", "in both ad1 and ad2", "both ad1 and ad2 preferentially", "ad1 and ad2 preferentially affect", "and ad2 preferentially affect the", "ad2 preferentially affect the ability", "preferentially affect the ability of", "affect the ability of hsf1", "the ability of hsf1 to", "ability of hsf1 to stimulate", "of hsf1 to stimulate transcriptional", "hsf1 to stimulate transcriptional initiation", "stimulate transcriptional initiation while", "transcriptional initiation while mutations", "initiation while mutations in", "while mutations in phenylalanine residues", "mutations in phenylalanine residues preferentially", "in phenylalanine residues preferentially affect", "phenylalanine residues preferentially affect stimulation", "residues preferentially affect stimulation of", "preferentially affect stimulation of elongation", "stimulation of elongation brown", "of elongation brown sa", "elongation brown sa et", "et al. 1998 .

activation", "al. 1998 .

activation of", "1998 .

activation of the", ".

activation of the dna", "

activation of the dna bound", "of the dna bound but", "the dna bound but transcriptionally", "dna bound but transcriptionally incompetent", "bound but transcriptionally incompetent hsf1", "but transcriptionally incompetent hsf1 is", "transcriptionally incompetent hsf1 is thought", "incompetent hsf1 is thought to", "hsf1 is thought to occur", "is thought to occur upon", "thought to occur upon stress", "to occur upon stress induced", "occur upon stress induced hsf1", "upon stress induced hsf1 phosphorylation", "stress induced hsf1 phosphorylation at", "induced hsf1 phosphorylation at several", "hsf1 phosphorylation at several serine", "phosphorylation at several serine residues", "several serine residues ding", "serine residues ding xz", "residues ding xz et", "ding xz et al. 1997", "et al. 1997 holmberg", "al. 1997 holmberg ci", "1997 holmberg ci et", "holmberg ci et al. 2001", "et al. 2001 guettouche", "al. 2001 guettouche t", "2001 guettouche t et", "guettouche t et al. 2005", "t et al. 2005 .", "et al. 2005 . in", "al. 2005 . in cells", "2005 . in cells exposed", ". in cells exposed to", "in cells exposed to heat", "exposed to heat acquisition", "to heat acquisition of", "heat acquisition of hse", "acquisition of hse dna binding", "of hse dna binding activity", "hse dna binding activity was", "dna binding activity was observed", "binding activity was observed to", "activity was observed to precede", "was observed to precede phosphorylation", "observed to precede phosphorylation of", "to precede phosphorylation of hsf1", "phosphorylation of hsf1 cotto", "of hsf1 cotto jj", "hsf1 cotto jj et", "et al. 1996 kline", "al. 1996 kline mp", "1996 kline mp &", "kline mp & morimoto ri", "mp & morimoto ri 1997", "& morimoto ri 1997 .", "morimoto ri 1997 . while", "ri 1997 . while there", "1997 . while there is", ". while there is a", "while there is a sufficient", "there is a sufficient evidence", "is a sufficient evidence to", "a sufficient evidence to suggest", "sufficient evidence to suggest that", "evidence to suggest that phosphorylation", "to suggest that phosphorylation of", "suggest that phosphorylation of hsf1", "that phosphorylation of hsf1 is", "phosphorylation of hsf1 is essential", "of hsf1 is essential to", "hsf1 is essential to modulate", "is essential to modulate hsf1", "essential to modulate hsf1 transactiviting", "to modulate hsf1 transactiviting capacity", "hsf1 transactiviting capacity mechanisms", "transactiviting capacity mechanisms behind", "capacity mechanisms behind stress", "mechanisms behind stress stimuli and", "behind stress stimuli and kinases/phosphatases", "stress stimuli and kinases/phosphatases involved", "stimuli and kinases/phosphatases involved have", "and kinases/phosphatases involved have not", "kinases/phosphatases involved have not been", "involved have not been clearly", "have not been clearly established." ] }, { "record_id": "GLY_000594_1_923", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "352230", "r hsa", "hsa 352230", "r hsa 352230" ] }, { "record_id": "GLY_000594_1_923", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "amino acid", "acid transport", "transport across", "across the", "the plasma", "plasma membrane", "amino acid transport", "acid transport across", "transport across the", "across the plasma", "the plasma membrane", "amino acid transport across", "acid transport across the", "transport across the plasma", "across the plasma membrane", "amino acid transport across the", "acid transport across the plasma", "transport across the plasma membrane", "across plasma", "plasma membranes", "membranes is", "is critical", "critical to", "to the", "the uptake", "uptake of", "of these", "these molecules", "molecules from", "from the", "the gut", "to their", "their reabsortion", "reabsortion in", "in the", "the kidney", "kidney proximal", "proximal tubulues", "and to", "their 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here", "is annotated here broer", "annotated here broer 2008", "here broer 2008 ." ] }, { "record_id": "GLY_000594_1_924", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "354192", "r hsa", "hsa 354192", "r hsa 354192" ] }, { "record_id": "GLY_000594_1_924", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "integrin signaling", "integrins are", "are a", "a major", "major family", "family of", "of cell", "cell surface", "surface receptors", "receptors that", "that modulate", "modulate cell", "cell adhesion", "proliferation and", "and survival", "survival through", "through interaction", "interaction with", "with the", "the extracellular", "extracellular matrix", "and the", "the actin", "actin cytoskeleton.", "are type", "type 1", "1 transmembrane", "transmembrane proteins", "proteins that", "that exist", "exist at", "at the", "the cell", "surface as", "as heterodimers", "heterodimers of", "of alpha", "alpha and", "and beta", "beta subunits", "of which", "which there", "there are", "are 18", "18 and", "and 8", "8 different", "different isoforms", "in human", "human cells.", "cells. in", "in addition", "addition to", "to their", "their mechanical", "mechanical role", "role in", "in mediating", "mediating contact", "contact between", "between the", "the ecm", "ecm and", "the cytoskeleton", "integrins also", "also modulate", "modulate intracellular", "intracellular signaling", "signaling pathways", "pathways governing", "governing cytoskeletal", "cytoskeletal rearrangements", "rearrangements and", "and pro", "pro survival", "survival and", "and mitogenic", "mitogenic signaling", "reviewed in", "in hehlgans", "hehlgans et", "et al", "harburger and", "and calderwood", "ata and", "and antonescu", "2017 .", ".
in", "
in this", "this pathway", "we describe", "describe signaling", "signaling through", "through integrin", "integrin alphaiib", "alphaiib beta3", "beta3 as", "as a", "a representative", "representative example.
", "example.
at", "the sites", "sites of", "of vascular", "vascular injury", "injury bioactive", "bioactive molecules", "molecules such", "such as", "as thrombin", "fibrinogen and", "and thrombospondin", "thrombospondin are", "are generated", "secreted or", "or exposed.", "exposed. these", "these stimuli", "stimuli activate", "activate platelets", "converting the", "the major", "major platelet", "platelet integrin", "integrin alphaiibbeta3", "alphaiibbeta3 from", "from a", "a resting", "resting state", "state to", "to an", "an active", "active conformation", "in a", "a process", "process termed", "termed integrin", "integrin priming", "priming or", "or 'inside", "'inside out", "out signalling'.", "signalling'. integrin", "integrin activation", "activation refers", "refers to", "to the", "the change", "change required", "required to", "to enhance", "enhance ligand", "ligand binding", "binding activity.", "activity. the", "the activated", "activated alphaiibbeta3", "alphaiibbeta3 interacts", "interacts with", "the fibrinogen", "and links", "links platelets", "platelets together", "together in", "in an", "an aggregate", "aggregate to", "to form", "form a", "a platelet", "platelet plug.", "plug. alphaiibbeta3", "alphaiibbeta3 bound", "bound to", "to fibrin", "fibrin generates", "generates more", "more intracellular", "intracellular signals", "outside in", "in signalling", "causing further", "further platelet", "platelet activation", "activation and", "and platelet", "platelet plug", "plug retraction.", "retraction.
in", "
in the", "the resting", "state the", "the alpha", "beta tails", "tails are", "are close", "close together.", "this interaction", "interaction keeps", "keeps the", "the membrane", "membrane proximal", "proximal regions", "regions in", "a bent", "bent conformation", "conformation that", "that maintains", "maintains alphaiibbeta3", "alphaiibbeta3 in", "a low", "low affinity", "affinity state.", "state.
integrin", "
integrin alphaiibbeta3", "alphaiibbeta3 is", "is released", "released from", "from its", "its inactive", "inactive state", "state by", "by interaction", "the protein", "protein talin.", "talin. talin", "talin interacts", "the beta3", "beta3 cytoplasmic", "cytoplasmic domain", "domain and", "and disrupts", "disrupts the", "the salt", "salt bridge", "bridge between", "beta chains.", "chains. this", "this separation", "separation in", "in the", "the cytoplasmic", "cytoplasmic regions", "regions triggers", "triggers the", "the conformational", "conformational change", "change in", "extracellular domain", "domain that", "that increases", "increases its", "its affinity", "affinity to", "to fibrinogen.", "fibrinogen.
much", "
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", "integrins are a", "are a major", "a major family", "major family of", "family of cell", "of cell surface", "cell surface receptors", "surface receptors that", "receptors that modulate", "that modulate cell", "modulate cell adhesion", "adhesion migration", "migration proliferation", "proliferation and survival", "and survival through", "survival through interaction", "through interaction with", "interaction with the", "with the extracellular", "the extracellular matrix", "matrix ecm", "and the actin", "the actin cytoskeleton.", "cytoskeleton. integrins", "integrins are type", "are type 1", "type 1 transmembrane", "1 transmembrane proteins", "transmembrane proteins that", "proteins that exist", "that exist at", "exist at the", "at the cell", "the cell surface", "cell surface as", "surface as heterodimers", "as heterodimers of", "heterodimers of alpha", "of alpha and", "alpha and beta", "and beta subunits", "subunits of", "of which there", "which there are", "there are 18", "are 18 and", "18 and 8", "and 8 different", "8 different isoforms", "isoforms respectively", "respectively in", "in human cells.", "human cells. in", "cells. in addition", "in addition to", "addition to their", "to their mechanical", "their mechanical role", "mechanical role in", "role in mediating", "in mediating contact", "mediating contact between", "contact between the", "between the ecm", "the ecm and", "ecm and the", "and the cytoskeleton", "cytoskeleton integrins", "integrins also modulate", "also modulate intracellular", "modulate intracellular signaling", "intracellular signaling pathways", "signaling pathways governing", "pathways governing cytoskeletal", "governing cytoskeletal rearrangements", "cytoskeletal rearrangements and", "rearrangements and pro", "and pro survival", "pro survival and", "survival and mitogenic", "and mitogenic signaling", "signaling reviewed", "reviewed in hehlgans", "in hehlgans et", "hehlgans et al", "al 2007", "2007 harburger", "harburger and calderwood", "calderwood 2009", "2009 ata", "ata and antonescu", "antonescu 2017", "2017 .
in", ".
in this", "
in this pathway", "pathway we", "we describe signaling", "describe signaling through", "signaling through integrin", "through integrin alphaiib", "integrin alphaiib beta3", "alphaiib beta3 as", "beta3 as a", "as a representative", "a representative example.
", "representative example.
at", "example.
at the", "at the sites", "the sites of", "sites of vascular", "of vascular injury", "vascular injury bioactive", "injury bioactive molecules", "bioactive molecules such", "molecules such as", "such as thrombin", "thrombin adp", "adp collagen", "collagen fibrinogen", "fibrinogen and thrombospondin", "and thrombospondin are", "thrombospondin are generated", "generated secreted", "secreted or exposed.", "or exposed. these", "exposed. these stimuli", "these stimuli activate", "stimuli activate platelets", "platelets converting", "converting the major", "the major platelet", "major platelet integrin", "platelet integrin alphaiibbeta3", "integrin alphaiibbeta3 from", "alphaiibbeta3 from a", "from a resting", "a resting state", "resting state to", "state to an", "to an active", "an active conformation", "conformation in", "in a process", "a process termed", "process termed integrin", "termed integrin priming", "integrin priming or", "priming or 'inside", "or 'inside out", "'inside out signalling'.", "out signalling'. integrin", "signalling'. integrin activation", "integrin activation refers", "activation refers to", "refers to the", "to the change", "the change required", "change required to", "required to enhance", "to enhance ligand", "enhance ligand binding", "ligand binding activity.", "binding activity. the", "activity. the activated", "the activated alphaiibbeta3", "activated alphaiibbeta3 interacts", "alphaiibbeta3 interacts with", "interacts with the", "with the fibrinogen", "the fibrinogen and", "fibrinogen and links", "and links platelets", "links platelets together", "platelets together in", "together in an", "in an aggregate", "an aggregate to", "aggregate to form", "to form a", "form a platelet", "a platelet plug.", "platelet plug. alphaiibbeta3", "plug. alphaiibbeta3 bound", "alphaiibbeta3 bound to", "bound to fibrin", "to fibrin generates", "fibrin generates more", "generates more intracellular", "more intracellular signals", "signals outside", "outside in signalling", "causing further platelet", "further platelet activation", "platelet activation and", "activation and platelet", "and platelet plug", "platelet plug retraction.", "plug retraction.
in", "retraction.
in the", "
in the resting", "the resting state", "resting state the", "state the alpha", "the alpha and", "and beta tails", "beta tails are", "tails are close", "are close together.", "together. this", "this interaction keeps", "interaction keeps the", "keeps the membrane", "the membrane proximal", "membrane proximal regions", "proximal regions in", "regions in a", "in a bent", "a bent conformation", "bent conformation that", "conformation that maintains", "that maintains alphaiibbeta3", "maintains alphaiibbeta3 in", "alphaiibbeta3 in a", "in a low", "a low affinity", "low affinity state.", "affinity state.
integrin", "state.
integrin alphaiibbeta3", "
integrin alphaiibbeta3 is", "alphaiibbeta3 is released", "is released from", "released from its", "from its inactive", "its inactive state", "inactive state by", "state by interaction", "by interaction with", "with the protein", "the protein talin.", "protein talin. talin", "talin. talin interacts", "talin interacts with", "with the beta3", "the beta3 cytoplasmic", "beta3 cytoplasmic domain", "cytoplasmic domain and", "domain and disrupts", "and disrupts the", "disrupts the salt", "the salt bridge", "salt bridge between", "bridge between the", "between the alpha", "and beta chains.", "beta chains. this", "chains. this separation", "this separation in", "separation in the", "in the cytoplasmic", "the cytoplasmic regions", "cytoplasmic regions triggers", "regions triggers the", "triggers the conformational", "the conformational change", "conformational change in", "change in the", "in the extracellular", "the extracellular domain", "extracellular domain that", "domain that increases", "that increases its", "increases its affinity", "its affinity to", "affinity to fibrinogen.", "to fibrinogen.
much", "fibrinogen.
much of", "
much of talin", "of talin exists", "talin exists in", "exists in an", "in an inactive", "an inactive cytosolic", "inactive cytosolic pool", "pool and", "and the rap1", "the rap1 interacting", "rap1 interacting adaptor", "interacting adaptor molecule", "molecule riam", "riam is", "is implicated in", "implicated in talin", "in talin activation", "talin activation and", "activation and translocation", "and translocation to", "translocation to beta3", "to beta3 integrin", "beta3 integrin cytoplasmic", "integrin cytoplasmic domain.
", "integrins are a major", "are a major family", "a major family of", "major family of cell", "family of cell surface", "of cell surface receptors", "cell surface receptors that", "surface receptors that modulate", "receptors that modulate cell", "that modulate cell adhesion", "cell adhesion migration", "migration proliferation and", "proliferation and survival through", "and survival through interaction", "survival through interaction with", "through interaction with the", "interaction with the extracellular", "with the extracellular matrix", "extracellular matrix ecm", "and the actin cytoskeleton.", "actin cytoskeleton. integrins", "cytoskeleton. integrins are", "integrins are type 1", "are type 1 transmembrane", "type 1 transmembrane proteins", "1 transmembrane proteins that", "transmembrane proteins that exist", "proteins that exist at", "that exist at the", "exist at the cell", "at the cell surface", "the cell surface as", "cell surface as heterodimers", "surface as heterodimers of", "as heterodimers of alpha", "heterodimers of alpha and", "of alpha and beta", "alpha and beta subunits", "beta subunits of", "subunits of which", "of which there are", "which there are 18", "there are 18 and", "are 18 and 8", "18 and 8 different", "and 8 different isoforms", "different isoforms respectively", "respectively in human", "in human cells. in", "human cells. in addition", "cells. in addition to", "in addition to their", "addition to their mechanical", "to their mechanical role", "their mechanical role in", "mechanical role in mediating", "role in mediating contact", "in mediating contact between", "mediating contact between the", "contact between the ecm", "between the ecm and", "the ecm and the", "ecm and the cytoskeleton", "the cytoskeleton integrins", "cytoskeleton integrins also", "integrins also modulate intracellular", "also modulate intracellular signaling", "modulate intracellular signaling pathways", "intracellular signaling pathways governing", "signaling pathways governing cytoskeletal", "pathways governing cytoskeletal rearrangements", "governing cytoskeletal rearrangements and", "cytoskeletal rearrangements and pro", "rearrangements and pro survival", "and pro survival and", "pro survival and mitogenic", "survival and mitogenic signaling", "mitogenic signaling reviewed", "signaling reviewed in", "reviewed in hehlgans et", "in hehlgans et al", "et al 2007", "2007 harburger and", "and calderwood 2009", "2009 ata and", "and antonescu 2017", "antonescu 2017 .", "2017 .
in this", ".
in this pathway", "this pathway we", "pathway we describe", "we describe signaling through", "describe signaling through integrin", "signaling through integrin alphaiib", "through integrin alphaiib beta3", "integrin alphaiib beta3 as", "alphaiib beta3 as a", "beta3 as a representative", "as a representative example.
", "a representative example.
at", "representative example.
at the", "example.
at the sites", "at the sites of", "the sites of vascular", "sites of vascular injury", "of vascular injury bioactive", "vascular injury bioactive molecules", "injury bioactive molecules such", "bioactive molecules such as", "molecules such as thrombin", "as thrombin adp", "collagen fibrinogen and", "fibrinogen and thrombospondin are", "and thrombospondin are generated", "are generated secreted", "generated secreted or", "secreted or exposed. these", "or exposed. these stimuli", "exposed. these stimuli activate", "these stimuli activate platelets", "activate platelets converting", "platelets converting the", "converting the major platelet", "the major platelet integrin", "major platelet integrin alphaiibbeta3", "platelet integrin alphaiibbeta3 from", "integrin alphaiibbeta3 from a", "alphaiibbeta3 from a resting", "from a resting state", "a resting state to", "resting state to an", "state to an active", "to an active conformation", "active conformation in", "conformation in a", "in a process termed", "a process termed integrin", "process termed integrin priming", "termed integrin priming or", "integrin priming or 'inside", "priming or 'inside out", "or 'inside out signalling'.", "'inside out signalling'. integrin", "out signalling'. integrin activation", "signalling'. integrin activation refers", "integrin activation refers to", "activation refers to the", "refers to the change", "to the change required", "the change required to", "change required to enhance", "required to enhance ligand", "to enhance ligand binding", "enhance ligand binding activity.", "ligand binding activity. the", "binding activity. the activated", "activity. the activated alphaiibbeta3", "the activated alphaiibbeta3 interacts", "activated alphaiibbeta3 interacts with", "alphaiibbeta3 interacts with the", "interacts with the fibrinogen", "with the fibrinogen and", "the fibrinogen and links", "fibrinogen and links platelets", "and links platelets together", "links platelets together in", "platelets together in an", "together in an aggregate", "in an aggregate to", "an aggregate to form", "aggregate to form a", "to form a platelet", "form a platelet plug.", "a platelet plug. alphaiibbeta3", "platelet plug. alphaiibbeta3 bound", "plug. alphaiibbeta3 bound to", "alphaiibbeta3 bound to fibrin", "bound to fibrin generates", "to fibrin generates more", "fibrin generates more intracellular", "generates more intracellular signals", "intracellular signals outside", "signals outside in", "signalling causing", "causing further platelet activation", "further platelet activation and", "platelet activation and platelet", "activation and platelet plug", "and platelet plug retraction.", "platelet plug retraction.
in", "plug retraction.
in the", "retraction.
in the resting", "
in the resting state", "the resting state the", "resting state the alpha", "state the alpha and", "the alpha and beta", "alpha and beta tails", "and beta tails are", "beta tails are close", "tails are close together.", "close together. this", "together. this interaction", "this interaction keeps the", "interaction keeps the membrane", "keeps the membrane proximal", "the membrane proximal regions", "membrane proximal regions in", "proximal regions in a", "regions in a bent", "in a bent conformation", "a bent conformation that", "bent conformation that maintains", "conformation that maintains alphaiibbeta3", "that maintains alphaiibbeta3 in", "maintains alphaiibbeta3 in a", "alphaiibbeta3 in a low", "in a low affinity", "a low affinity state.", "low affinity state.
integrin", "affinity state.
integrin alphaiibbeta3", "state.
integrin alphaiibbeta3 is", "
integrin alphaiibbeta3 is released", "alphaiibbeta3 is released from", "is released from its", "released from its inactive", "from its inactive state", "its inactive state by", "inactive state by interaction", "state by interaction with", "by interaction with the", "interaction with the protein", "with the protein talin.", "the protein talin. talin", "protein talin. talin interacts", "talin. talin interacts with", "talin interacts with the", "interacts with the beta3", "with the beta3 cytoplasmic", "the beta3 cytoplasmic domain", "beta3 cytoplasmic domain and", "cytoplasmic domain and disrupts", "domain and disrupts the", "and disrupts the salt", "disrupts the salt bridge", "the salt bridge between", "salt bridge between the", "bridge between the alpha", "between the alpha and", "alpha and beta chains.", "and beta chains. this", "beta chains. this separation", "chains. this separation in", "this separation in the", "separation in the cytoplasmic", "in the cytoplasmic regions", "the cytoplasmic regions triggers", "cytoplasmic regions triggers the", "regions triggers the conformational", "triggers the conformational change", "the conformational change in", "conformational change in the", "change in the extracellular", "in the extracellular domain", "the extracellular domain that", "extracellular domain that increases", "domain that increases its", "that increases its affinity", "increases its affinity to", "its affinity to fibrinogen.", "affinity to fibrinogen.
much", "to fibrinogen.
much of", "fibrinogen.
much of talin", "
much of talin exists", "of talin exists in", "talin exists in an", "exists in an inactive", "in an inactive cytosolic", "an inactive cytosolic pool", "cytosolic pool and", "pool and the", "and the rap1 interacting", "the rap1 interacting adaptor", "rap1 interacting adaptor molecule", "adaptor molecule riam", "riam is implicated", "is implicated in talin", "implicated in talin activation", "in talin activation and", "talin activation and translocation", "activation and translocation to", "and translocation to beta3", "translocation to beta3 integrin", "to beta3 integrin cytoplasmic", "beta3 integrin cytoplasmic domain.
", "integrins are a major family", "are a major family of", "a major family of cell", "major family of cell surface", "family of cell surface receptors", "of cell surface receptors that", "cell surface receptors that modulate", "surface receptors that modulate cell", "receptors that modulate cell adhesion", "modulate cell adhesion migration", "adhesion migration proliferation", "migration proliferation and survival", "proliferation and survival through interaction", "and survival through interaction with", "survival through interaction with the", "through interaction with the extracellular", "interaction with the extracellular matrix", "the extracellular matrix ecm", "matrix ecm and", "ecm and the actin", "the actin cytoskeleton. integrins", "actin cytoskeleton. integrins are", "cytoskeleton. integrins are type", "integrins are type 1 transmembrane", "are type 1 transmembrane proteins", "type 1 transmembrane proteins that", "1 transmembrane proteins that exist", "transmembrane proteins that exist at", "proteins that exist at the", "that exist at the cell", "exist at the cell surface", "at the cell surface as", "the cell surface as heterodimers", "cell surface as heterodimers of", "surface as heterodimers of alpha", "as heterodimers of alpha and", "heterodimers of alpha and beta", "of alpha and beta subunits", "and beta subunits of", "beta subunits of which", "subunits of which there", "of which there are 18", "which there are 18 and", "there are 18 and 8", "are 18 and 8 different", "18 and 8 different isoforms", "8 different isoforms respectively", "isoforms respectively in", "respectively in human cells.", "in human cells. in addition", "human cells. in addition to", "cells. in addition to their", "in addition to their mechanical", "addition to their mechanical role", "to their mechanical role in", "their mechanical role in mediating", "mechanical role in mediating contact", "role in mediating contact between", "in mediating contact between the", "mediating contact between the ecm", "contact between the ecm and", "between the ecm and the", "the ecm and the cytoskeleton", "and the cytoskeleton integrins", "the cytoskeleton integrins also", "cytoskeleton integrins also modulate", "integrins also modulate intracellular signaling", "also modulate intracellular signaling pathways", "modulate intracellular signaling pathways governing", "intracellular signaling pathways governing cytoskeletal", "signaling pathways governing cytoskeletal rearrangements", "pathways governing cytoskeletal rearrangements and", "governing cytoskeletal rearrangements and pro", "cytoskeletal rearrangements and pro survival", "rearrangements and pro survival and", "and pro survival and mitogenic", "pro survival and mitogenic signaling", "and mitogenic signaling reviewed", "mitogenic signaling reviewed in", "signaling reviewed in hehlgans", "reviewed in hehlgans et al", "hehlgans et al 2007", "al 2007 harburger", "2007 harburger and calderwood", "harburger and calderwood 2009", "calderwood 2009 ata", "2009 ata and antonescu", "ata and antonescu 2017", "and antonescu 2017 .", "antonescu 2017 .
in", "2017 .
in this pathway", "
in this pathway we", "this pathway we describe", "pathway we describe signaling", "we describe signaling through integrin", "describe signaling through integrin alphaiib", "signaling through integrin alphaiib beta3", "through integrin alphaiib beta3 as", "integrin alphaiib beta3 as a", "alphaiib beta3 as a representative", "beta3 as a representative example.
", "as a representative example.
at", "a representative example.
at the", "representative example.
at the sites", "example.
at the sites of", "at the sites of vascular", "the sites of vascular injury", "sites of vascular injury bioactive", "of vascular injury bioactive molecules", "vascular injury bioactive molecules such", "injury bioactive molecules such as", "bioactive molecules such as thrombin", "such as thrombin adp", "thrombin adp collagen", "adp collagen fibrinogen", "collagen fibrinogen and thrombospondin", "fibrinogen and thrombospondin are generated", "thrombospondin are generated secreted", "are generated secreted or", "generated secreted or exposed.", "secreted or exposed. these stimuli", "or exposed. these stimuli activate", "exposed. these stimuli activate platelets", "stimuli activate platelets converting", "activate platelets converting the", "platelets converting the major", "converting the major platelet integrin", "the major platelet integrin alphaiibbeta3", "major platelet integrin alphaiibbeta3 from", "platelet integrin alphaiibbeta3 from a", "integrin alphaiibbeta3 from a resting", "alphaiibbeta3 from a resting state", "from a resting state to", "a resting state to an", "resting state to an active", "state to an active conformation", "an active conformation in", "active conformation in a", "conformation in a process", "in a process termed integrin", "a process termed integrin priming", "process termed integrin priming or", "termed integrin priming or 'inside", "integrin priming or 'inside out", "priming or 'inside out signalling'.", "or 'inside out signalling'. integrin", "'inside out signalling'. integrin activation", "out signalling'. integrin activation refers", "signalling'. integrin activation refers to", "integrin activation refers to the", "activation refers to the change", "refers to the change required", "to the change required to", "the change required to enhance", "change required to enhance ligand", "required to enhance ligand binding", "to enhance ligand binding activity.", "enhance ligand binding activity. the", "ligand binding activity. the activated", "binding activity. the activated alphaiibbeta3", "activity. the activated alphaiibbeta3 interacts", "the activated alphaiibbeta3 interacts with", "activated alphaiibbeta3 interacts with the", "alphaiibbeta3 interacts with the fibrinogen", "interacts with the fibrinogen and", "with the fibrinogen and links", "the fibrinogen and links platelets", "fibrinogen and links platelets together", "and links platelets together in", "links platelets together in an", "platelets together in an aggregate", "together in an aggregate to", "in an aggregate to form", "an aggregate to form a", "aggregate to form a platelet", "to form a platelet plug.", "form a platelet plug. alphaiibbeta3", "a platelet plug. alphaiibbeta3 bound", "platelet plug. alphaiibbeta3 bound to", "plug. alphaiibbeta3 bound to fibrin", "alphaiibbeta3 bound to fibrin generates", "bound to fibrin generates more", "to fibrin generates more intracellular", "fibrin generates more intracellular signals", "more intracellular signals outside", "intracellular signals outside in", "signals outside in signalling", "in signalling causing", "signalling causing further", "causing further platelet activation and", "further platelet activation and platelet", "platelet activation and platelet plug", "activation and platelet plug retraction.", "and platelet plug retraction.
in", "platelet plug retraction.
in the", "plug retraction.
in the resting", "retraction.
in the resting state", "
in the resting state the", "the resting state the alpha", "resting state the alpha and", "state the alpha and beta", "the alpha and beta tails", "alpha and beta tails are", "and beta tails are close", "beta tails are close together.", "are close together. this", "close together. this interaction", "together. this interaction keeps", "this interaction keeps the membrane", "interaction keeps the membrane proximal", "keeps the membrane proximal regions", "the membrane proximal regions in", "membrane proximal regions in a", "proximal regions in a bent", "regions in a bent conformation", "in a bent conformation that", "a bent conformation that maintains", "bent conformation that maintains alphaiibbeta3", "conformation that maintains alphaiibbeta3 in", "that maintains alphaiibbeta3 in a", "maintains alphaiibbeta3 in a low", "alphaiibbeta3 in a low affinity", "in a low affinity state.", "a low affinity state.
integrin", "low affinity state.
integrin alphaiibbeta3", "affinity state.
integrin alphaiibbeta3 is", "state.
integrin alphaiibbeta3 is released", "
integrin alphaiibbeta3 is released from", "alphaiibbeta3 is released from its", "is released from its inactive", "released from its inactive state", "from its inactive state by", "its inactive state by interaction", "inactive state by interaction with", "state by interaction with the", "by interaction with the protein", "interaction with the protein talin.", "with the protein talin. talin", "the protein talin. talin interacts", "protein talin. talin interacts with", "talin. talin interacts with the", "talin interacts with the beta3", "interacts with the beta3 cytoplasmic", "with the beta3 cytoplasmic domain", "the beta3 cytoplasmic domain and", "beta3 cytoplasmic domain and disrupts", "cytoplasmic domain and disrupts the", "domain and disrupts the salt", "and disrupts the salt bridge", "disrupts the salt bridge between", "the salt bridge between the", "salt bridge between the alpha", "bridge between the alpha and", "between the alpha and beta", "the alpha and beta chains.", "alpha and beta chains. this", "and beta chains. this separation", "beta chains. this separation in", "chains. this separation in the", "this separation in the cytoplasmic", "separation in the cytoplasmic regions", "in the cytoplasmic regions triggers", "the cytoplasmic regions triggers the", "cytoplasmic regions triggers the conformational", "regions triggers the conformational change", "triggers the conformational change in", "the conformational change in the", "conformational change in the extracellular", "change in the extracellular domain", "in the extracellular domain that", "the extracellular domain that increases", "extracellular domain that increases its", "domain that increases its affinity", "that increases its affinity to", "increases its affinity to fibrinogen.", "its affinity to fibrinogen.
much", "affinity to fibrinogen.
much of", "to fibrinogen.
much of talin", "fibrinogen.
much of talin exists", "
much of talin exists in", "of talin exists in an", "talin exists in an inactive", "exists in an inactive cytosolic", "in an inactive cytosolic pool", "inactive cytosolic pool and", "cytosolic pool and the", "pool and the rap1", "and the rap1 interacting adaptor", "the rap1 interacting adaptor molecule", "interacting adaptor molecule riam", "molecule riam is", "riam is implicated in", "is implicated in talin activation", "implicated in talin activation and", "in talin activation and translocation", "talin activation and translocation to", "activation and translocation to beta3", "and translocation to beta3 integrin", "translocation to beta3 integrin cytoplasmic", "to beta3 integrin cytoplasmic domain.
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"defective chst6 nakazawa et", "chst6 nakazawa et al.", "et al. 1984 results", "al. 1984 results in", "1984 results in unsulfated", "results in unsulfated keratan deposited", "in unsulfated keratan deposited within", "unsulfated keratan deposited within the", "keratan deposited within the intracellular", "deposited within the intracellular space", "within the intracellular space and", "the intracellular space and the", "intracellular space and the extracellular", "space and the extracellular corneal", "and the extracellular corneal stroma", "the extracellular corneal stroma leading", "extracellular corneal stroma leading to", "corneal stroma leading to macular", "stroma leading to macular dystrophy", "to macular dystrophy corneal", "macular dystrophy corneal type", "dystrophy corneal type i", "corneal type i mcdc1", "i mcdc1 mim:217800", "mcdc1 mim:217800 . mcdc1", "mim:217800 . mcdc1 is an", "217800 . mcdc1 is an", ". mcdc1 is an early", "mcdc1 is an early onset", "an early onset 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deficient glycoprotein", "called carbohydrate deficient glycoprotein syndromes", "deficient glycoprotein syndromes cdgss", "cdgss are a", "are a group of hereditary", "a group of hereditary multisystem", "group of hereditary multisystem disorders.", "of hereditary multisystem disorders. they", "hereditary multisystem disorders. they are", "multisystem disorders. they are characterized", "disorders. they are characterized biochemically", "they are characterized biochemically by", "are characterized biochemically by hypoglycosylation", "characterized biochemically by hypoglycosylation of", "biochemically by hypoglycosylation of glycoproteins", "hypoglycosylation of glycoproteins diagnosed", "of glycoproteins diagnosed by", "glycoproteins diagnosed by isoelectric", "by isoelectric focusing ief", "focusing ief of", "ief of serum transferrin.", "of serum transferrin. there are", "serum transferrin. there are two", "transferrin. there are two types", "there are two types of", "are two types 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protein bound", "processing of protein bound glycans.", "of protein bound glycans. clinical", "protein bound glycans. clinical symptoms", "bound glycans. clinical symptoms are", "glycans. clinical symptoms are dominated", "clinical symptoms are dominated by", "symptoms are dominated by severe", "are dominated by severe psychomotor", "dominated by severe psychomotor and", "by severe psychomotor and mental", "severe psychomotor and mental retardation", "and mental retardation as", "mental retardation as well", "retardation as well as", "as well as blood coagulation", "well as blood coagulation abnormalities", "blood coagulation abnormalities jaeken", "coagulation abnormalities jaeken 2013", "abnormalities jaeken 2013 .", "jaeken 2013 . b4galt1 cdg", ". b4galt1 cdg cdg", "b4galt1 cdg cdg type", "cdg cdg type iid", "cdg type iid is", "type iid is a", "iid is a multisystem", "a multisystem disease characterized", "multisystem disease characterized by", "disease characterized by dysmorphic", "by dysmorphic features hydrocephalus", "features hydrocephalus hypotonia", "hydrocephalus hypotonia and blood", "hypotonia and blood clotting abnormalities", "blood clotting abnormalities hansske", "clotting abnormalities hansske et", "abnormalities hansske et al.", "hansske et al. 2002 ." ] }, { "record_id": "GLY_000594_1_932", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3656532", "r hsa", "hsa 3656532", "r hsa 3656532" ] }, { "record_id": "GLY_000594_1_932", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tgfbr1 kd", "kd mutants", "mutants in", "in cancer", "tgfbr1 kd mutants", "kd mutants in", "mutants in cancer", "tgfbr1 kd mutants in", "kd mutants in cancer", "tgfbr1 kd mutants in cancer", "mutations in", "in the", "the kinase", "kinase domain", "of tgf", "tgf beta", "beta receptor", "receptor 1", "have been", "been found", "found in", "in ferguson", "ferguson smith", "smith tumor", "tumor i.e.", "i.e. multiple", "multiple self", "self healing", "healing squamous", "squamous epithelioma", "goudie et", "et al.", "al. 2011", "breast cancer", "chen et", "al. 1998", "ovarian cancer", "al. 2001", "and head", "head and", "and neck", "neck cancer", "2001 .", ". kd", "kd mutations", "mutations reported", "reported in", "in msse", "msse are", "are nonsense", "nonsense and", "and frameshift", "frameshift mutations", "mutations that", "that cause", "cause premature", "premature termination", "termination of", "of tgfbr1", "tgfbr1 translation", "resulting in", "in truncated", "truncated receptors", "receptors that", "that lack", "lack substantial", "substantial portions", "portions of", "of the", "or cause", "cause nonsense", "nonsense mediated", "mediated decay", "decay of", "of mutant", "mutant transcripts.", "transcripts. a", "a splice", "splice site", "site kd", "kd mutation", "mutation c.806", "c.806 2a>c", "2a>c is", "is predicted", "predicted to", "to result", "result in", "the skipping", "skipping of", "of exon", "exon 5", "5 and", "and the", "the absence", "absence of", "of kd", "kd amino", "amino acid", "acid residues", "residues 269", "269 324", "324 from", "from the", "the mutant", "mutant receptor.", "receptor. the", "the splice", "site mutant", "mutant is", "is expressed", "expressed at", "at the", "the cell", "cell surface", "surface but", "but unresponsive", "unresponsive to", "to tgf", "beta stimulation", "al. 2004", "2004 .


tgfbr1", ".


tgfbr1 kd", "in breast", "ovarian and", "cancer are", "are missense", "missense mutations", "and it", "it appears", "appears that", "that these", "these mutant", "mutant proteins", "proteins are", "are partially", "partially functional", "functional but", "but that", "that their", "their catalytic", "catalytic activity", "activity or", "or protein", "protein stability", "stability is", "is decreased", "al. 2001a", "2001a and", "and b", "b .", ". these", "these mutants", "mutants are", "are not", "not shown.", "mutations in the", "in the kinase", "the kinase domain", "domain kd", "kd of", "of tgf beta", "tgf beta receptor", "beta receptor 1", "1 tgfbr1", "tgfbr1 have", "have been found", "been found in", "found in ferguson", "in ferguson smith", "ferguson smith tumor", "smith tumor i.e.", "tumor i.e. multiple", "i.e. multiple self", "multiple self healing", "self healing squamous", "healing squamous epithelioma", "msse goudie", "goudie et al.", "et al. 2011", "cancer chen", "chen et al.", "et al. 1998", "et al. 2001", "2001 and", "and head and", "head and neck", "and neck cancer", "al. 2001 .", "2001 . kd", ". kd mutations", "kd mutations reported", "mutations reported in", "reported in msse", "in msse are", "msse are nonsense", "are nonsense and", "nonsense and frameshift", "and frameshift mutations", "frameshift mutations that", "mutations that cause", "that cause premature", "cause premature termination", "premature termination of", "termination of tgfbr1", "of tgfbr1 translation", "translation resulting", "resulting in truncated", "in truncated receptors", "truncated receptors that", "receptors that lack", "that lack substantial", "lack substantial portions", "substantial portions of", "portions of the", "of the kinase", "domain or", "or cause nonsense", "cause nonsense mediated", "nonsense mediated decay", "mediated decay of", "decay of mutant", "of mutant transcripts.", "mutant transcripts. a", "transcripts. a splice", "a splice site", "splice site kd", "site kd mutation", "kd mutation c.806", "mutation c.806 2a>c", "c.806 2a>c is", "2a>c is predicted", "is predicted to", "predicted to result", "to result in", "result in the", "in the skipping", "the skipping of", "skipping of exon", "of exon 5", "exon 5 and", "5 and the", "and the absence", "the absence of", "absence of kd", "of kd amino", "kd amino acid", "amino acid residues", "acid residues 269", "residues 269 324", "269 324 from", "324 from the", "from the mutant", "the mutant receptor.", "mutant receptor. the", "receptor. the splice", "the splice site", "splice site mutant", "site mutant is", "mutant is expressed", "is expressed at", "expressed at the", "at the cell", "the cell surface", "cell surface but", "surface but unresponsive", "but unresponsive to", "unresponsive to tgf", "to tgf beta", "tgf beta stimulation", "stimulation goudie", "et al. 2004", "al. 2004 .


tgfbr1", "2004 .


tgfbr1 kd", ".


tgfbr1 kd mutations", "reported in breast", "breast ovarian", "ovarian and head", "neck cancer are", "cancer are missense", "are missense mutations", "mutations and", "and it appears", "it appears that", "appears that these", "that these mutant", "these mutant proteins", "mutant proteins are", "proteins are partially", "are partially functional", "partially functional but", "functional but that", "but that their", "that their catalytic", "their catalytic activity", "catalytic activity or", "activity or protein", "or protein stability", "protein stability is", "stability is decreased", "decreased chen", "1998 chen", "et al. 2001a", "al. 2001a and", "2001a and b", "and b .", "b . these", ". these mutants", "these mutants are", "mutants are not", "are not shown.", "mutations in the kinase", "in the kinase domain", "kinase domain kd", "kd of tgf", "of tgf beta receptor", "tgf beta receptor 1", "receptor 1 tgfbr1", "tgfbr1 have been", "have been found in", "been found in ferguson", "found in ferguson smith", "in ferguson smith tumor", "ferguson smith tumor i.e.", "smith tumor i.e. multiple", "tumor i.e. multiple self", "i.e. multiple self healing", "multiple self healing squamous", "self healing squamous epithelioma", "epithelioma msse", "msse goudie et", "goudie et al. 2011", "2011 breast", "breast cancer chen", "cancer chen et", "chen et al. 1998", "1998 ovarian", "ovarian cancer chen", "chen et al. 2001", "al. 2001 and", "2001 and head", "and head and neck", "head and neck cancer", "neck cancer chen", "et al. 2001 .", "al. 2001 . kd", "2001 . kd mutations", ". kd mutations reported", "kd mutations reported in", "mutations reported in msse", "reported in msse are", "in msse are nonsense", "msse are nonsense and", "are nonsense and frameshift", "nonsense and frameshift mutations", "and frameshift mutations that", "frameshift mutations that cause", "mutations that cause premature", "that cause premature termination", "cause premature termination of", "premature termination of tgfbr1", "termination of tgfbr1 translation", "tgfbr1 translation resulting", "translation resulting in", "resulting in truncated receptors", "in truncated receptors that", "truncated receptors that lack", "receptors that lack substantial", "that lack substantial portions", "lack substantial portions of", "substantial portions of the", "portions of the kinase", "of the kinase domain", "kinase domain or", "domain or cause", "or cause nonsense mediated", "cause nonsense mediated decay", "nonsense mediated decay of", "mediated decay of mutant", "decay of mutant transcripts.", "of mutant transcripts. a", "mutant transcripts. a splice", "transcripts. a splice site", "a splice site kd", "splice site kd mutation", "site kd mutation c.806", "kd mutation c.806 2a>c", "mutation c.806 2a>c is", "c.806 2a>c is predicted", "2a>c is predicted to", "is predicted to result", "predicted to result in", "to result in the", "result in the skipping", "in the skipping of", "the skipping of exon", "skipping of exon 5", "of exon 5 and", "exon 5 and the", "5 and the absence", "and the absence of", "the absence of kd", "absence of kd amino", "of kd amino acid", "kd amino acid residues", "amino acid residues 269", "acid residues 269 324", "residues 269 324 from", "269 324 from the", "324 from the mutant", "from the mutant receptor.", "the mutant receptor. the", "mutant receptor. the splice", "receptor. the splice site", "the splice site mutant", "splice site mutant is", "site mutant is expressed", "mutant is expressed at", "is expressed at the", "expressed at the cell", "at the cell surface", "the cell surface but", "cell surface but unresponsive", "surface but unresponsive to", "but unresponsive to tgf", "unresponsive to tgf beta", "to tgf beta stimulation", "beta stimulation goudie", "stimulation goudie et", "goudie et al. 2004", "et al. 2004 .


tgfbr1", "al. 2004 .


tgfbr1 kd", "2004 .


tgfbr1 kd mutations", ".


tgfbr1 kd mutations reported", "mutations reported in breast", "in breast ovarian", "breast ovarian and", "ovarian and head and", "and neck cancer are", "neck cancer are missense", "cancer are missense mutations", "missense mutations and", "mutations and it", "and it appears that", "it appears that these", "appears that these mutant", "that these mutant proteins", "these mutant proteins are", "mutant proteins are partially", "proteins are partially functional", "are partially functional but", "partially functional but that", "functional but that their", "but that their catalytic", "that their catalytic activity", "their catalytic activity or", "catalytic activity or protein", "activity or protein stability", "or protein stability is", "protein stability is decreased", "is decreased chen", "decreased chen et", "al. 1998 chen", "1998 chen et", "chen et al. 2001a", "et al. 2001a and", "al. 2001a and b", "2001a and b .", "and b . these", "b . these mutants", ". these mutants are", "these mutants are not", "mutants are not shown.", "mutations in the kinase domain", "the kinase domain kd", "domain kd of", "kd of tgf beta", "of tgf beta receptor 1", "beta receptor 1 tgfbr1", "1 tgfbr1 have", "tgfbr1 have been found", "have been found in ferguson", "been found in ferguson smith", "found in ferguson smith tumor", "in ferguson smith tumor i.e.", "ferguson smith tumor i.e. multiple", "smith tumor i.e. multiple self", "tumor i.e. multiple self healing", "i.e. multiple self healing squamous", "multiple self healing squamous epithelioma", "squamous epithelioma msse", "msse goudie et al.", "al. 2011 breast", "2011 breast cancer", "breast cancer chen et", "cancer chen et al.", "al. 1998 ovarian", "1998 ovarian cancer", "ovarian cancer chen et", "et al. 2001 and", "al. 2001 and head", "2001 and head and", "and head and neck cancer", "and neck cancer chen", "neck cancer chen et", "chen et al. 2001 .", "et al. 2001 . kd", "al. 2001 . kd mutations", "2001 . kd mutations reported", ". kd mutations reported in", "kd mutations reported in msse", "mutations reported in msse are", "reported in msse are nonsense", "in msse are nonsense and", "msse are nonsense and frameshift", "are nonsense and frameshift mutations", "nonsense and frameshift mutations that", "and frameshift mutations that cause", "frameshift mutations that cause premature", "mutations that cause premature termination", "that cause premature termination of", "cause premature termination of tgfbr1", "premature termination of tgfbr1 translation", "of tgfbr1 translation resulting", "tgfbr1 translation resulting in", "translation resulting in truncated", "resulting in truncated receptors that", "in truncated receptors that lack", "truncated receptors that lack substantial", "receptors that lack substantial portions", "that lack substantial portions of", "lack substantial portions of the", "substantial portions of the kinase", "portions of the kinase domain", "the kinase domain or", "kinase domain or cause", "domain or cause nonsense", "or cause nonsense mediated decay", "cause nonsense mediated decay of", "nonsense mediated decay of mutant", "mediated decay of mutant transcripts.", "decay of mutant transcripts. a", "of mutant transcripts. a splice", "mutant transcripts. a splice site", "transcripts. a splice site kd", "a splice site kd mutation", "splice site kd mutation c.806", "site kd mutation c.806 2a>c", "kd mutation c.806 2a>c is", "mutation c.806 2a>c is predicted", "c.806 2a>c is predicted to", "2a>c is predicted to result", "is predicted to result in", "predicted to result in the", "to result in the skipping", "result in the skipping of", "in the skipping of exon", "the skipping of exon 5", "skipping of exon 5 and", "of exon 5 and the", "exon 5 and the absence", "5 and the absence of", "and the absence of kd", "the absence of kd amino", "absence of kd amino acid", "of kd amino acid residues", "kd amino acid residues 269", "amino acid residues 269 324", "acid residues 269 324 from", "residues 269 324 from the", "269 324 from the mutant", "324 from the mutant receptor.", "from the mutant receptor. the", "the mutant receptor. the splice", "mutant receptor. the splice site", "receptor. the splice site mutant", "the splice site mutant is", "splice site mutant is expressed", "site mutant is expressed at", "mutant is expressed at the", "is expressed at the cell", "expressed at the cell surface", "at the cell surface but", "the cell surface but unresponsive", "cell surface but unresponsive to", "surface but unresponsive to tgf", "but unresponsive to tgf beta", "unresponsive to tgf beta stimulation", "tgf beta stimulation goudie", "beta stimulation goudie et", "stimulation goudie et al.", "goudie et al. 2004 .


tgfbr1", "et al. 2004 .


tgfbr1 kd", "al. 2004 .


tgfbr1 kd mutations", "2004 .


tgfbr1 kd mutations reported", ".


tgfbr1 kd mutations reported in", "kd mutations reported in breast", "reported in breast ovarian", "in breast ovarian and", "breast ovarian and head", "ovarian and head and neck", "head and neck cancer are", "and neck cancer are missense", "neck cancer are missense mutations", "are missense mutations and", "missense mutations and it", "mutations and it appears", "and it appears that these", "it appears that these mutant", "appears that these mutant proteins", "that these mutant proteins are", "these mutant proteins are partially", "mutant proteins are partially functional", "proteins are partially functional but", "are partially functional but that", "partially functional but that their", "functional but that their catalytic", "but that their catalytic activity", "that their catalytic activity or", "their catalytic activity or protein", "catalytic activity or protein stability", "activity or protein stability is", "or protein stability is decreased", "stability is decreased chen", "is decreased chen et", "decreased chen et al.", "et al. 1998 chen", "al. 1998 chen et", "1998 chen et al.", "chen et al. 2001a and", "et al. 2001a and b", "al. 2001a and b .", "2001a and b . these", "and b . these mutants", "b . these mutants are", ". these mutants are not", "these mutants are not shown." ] }, { "record_id": "GLY_000594_1_933", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3656535", "r hsa", "hsa 3656535", "r hsa 3656535" ] }, { "record_id": "GLY_000594_1_933", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tgfbr1 lbd", "lbd mutants", "mutants in", "in cancer", "tgfbr1 lbd mutants", "lbd mutants in", "mutants in cancer", "tgfbr1 lbd mutants in", "lbd mutants in cancer", "tgfbr1 lbd mutants in cancer", "mutations in", "in the", "the ligand", "ligand binding", "binding domain", "of tgf", "tgf beta", "beta receptor", "receptor 1", "have been", "been reported", "reported as", "as germline", "germline mutations", "in ferguson", "ferguson smith", "smith tumor", "multiple self", "self healing", "healing squamous", "squamous epithelioma", "an autosomal", "autosomal dominant", "dominant skin", "skin cancer", "cancer condition", "smith et", "et al.", "al. 1934", "al. 1971", "with tumors", "tumors frequently", "frequently showing", "showing loss", "loss of", "of heterozygosity", "heterozygosity of", "of the", "the wild", "wild type", "type tgfbr1", "tgfbr1 allele", "goudie et", "al. 2011", "2011 .", ". somatic", "somatic mutations", "the lbd", "lbd of", "of tgfbr1", "tgfbr1 have", "reported in", "in esophageal", "esophageal carcinoma", "dulak et", "al. 2013", "2013 .", "mutations in the", "in the ligand", "the ligand binding", "ligand binding domain", "domain lbd", "of tgf beta", "tgf beta receptor", "beta receptor 1", "1 tgfbr1", "have been reported", "been reported as", "reported as germline", "as germline mutations", "germline mutations in", "mutations in ferguson", "in ferguson smith", "ferguson smith tumor", "tumor multiple", "multiple self healing", "self healing squamous", "healing squamous epithelioma", "an autosomal dominant", "autosomal dominant skin", "dominant skin cancer", "skin cancer condition", "condition ferguson", "ferguson smith et", "smith et al.", "et al. 1934", "1934 ferguson", "et al. 1971", "with tumors frequently", "tumors frequently showing", "frequently showing loss", "showing loss of", "loss of heterozygosity", "of heterozygosity of", "heterozygosity of the", "of the wild", "the wild type", "wild type tgfbr1", "type tgfbr1 allele", "allele goudie", "goudie et al.", "et al. 2011", "al. 2011 .", "2011 . somatic", ". somatic mutations", "somatic mutations in", "in the lbd", "the lbd of", "lbd of tgfbr1", "of tgfbr1 have", "tgfbr1 have been", "been reported in", "reported in esophageal", "in esophageal carcinoma", "carcinoma dulak", "dulak et al.", "et al. 2013", "al. 2013 .", "mutations in the ligand", "in the ligand binding", "the ligand binding domain", "binding domain lbd", "lbd of tgf", "of tgf beta receptor", "tgf beta receptor 1", "receptor 1 tgfbr1", "have been reported as", "been reported as germline", "reported as germline mutations", "as germline mutations in", "germline mutations in ferguson", "mutations in ferguson smith", "in ferguson smith tumor", "smith tumor multiple", "tumor multiple self", "multiple self healing squamous", "self healing squamous epithelioma", "epithelioma msse", "msse an", "an autosomal dominant skin", "autosomal dominant skin cancer", "dominant skin cancer condition", "cancer condition ferguson", "condition ferguson smith", "ferguson smith et al.", "smith et al. 1934", "al. 1934 ferguson", "1934 ferguson smith", "smith et al. 1971", "1971 with", "with tumors frequently showing", "tumors frequently showing loss", "frequently showing loss of", "showing loss of heterozygosity", "loss of heterozygosity of", "of heterozygosity of the", "heterozygosity of the wild", "of the wild type", "the wild type tgfbr1", "wild type tgfbr1 allele", "tgfbr1 allele goudie", "allele goudie et", "goudie et al. 2011", "et al. 2011 .", "al. 2011 . somatic", "2011 . somatic mutations", ". somatic mutations in", "somatic mutations in the", "mutations in the lbd", "in the lbd of", "the lbd of tgfbr1", "lbd of tgfbr1 have", "of tgfbr1 have been", "tgfbr1 have been reported", "have been reported in", "been reported in esophageal", "reported in esophageal carcinoma", "esophageal carcinoma dulak", "carcinoma dulak et", "dulak et al. 2013", "et al. 2013 .", "mutations in the ligand binding", "in the ligand binding domain", "ligand binding domain lbd", "domain lbd of", "lbd of tgf beta", "of tgf beta receptor 1", "beta receptor 1 tgfbr1", "1 tgfbr1 have", "have been reported as germline", "been reported as germline mutations", "reported as germline mutations in", "as germline mutations in ferguson", "germline mutations in ferguson smith", "mutations in ferguson smith 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"al. 2011 . somatic mutations", "2011 . somatic mutations in", ". somatic mutations in the", "somatic mutations in the lbd", "mutations in the lbd of", "in the lbd of tgfbr1", "the lbd of tgfbr1 have", "lbd of tgfbr1 have been", "of tgfbr1 have been reported", "tgfbr1 have been reported in", "have been reported in esophageal", "been reported in esophageal carcinoma", "in esophageal carcinoma dulak", "esophageal carcinoma dulak et", "carcinoma dulak et al.", "dulak et al. 2013 ." ] }, { "record_id": "GLY_000594_1_934", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "372708", "r hsa", "hsa 372708", "r hsa 372708" ] }, { "record_id": "GLY_000594_1_934", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "p130cas linkage", "linkage to", "to mapk", "mapk signaling", "signaling for", "for integrins", "p130cas linkage to", "linkage to mapk", "to mapk signaling", "mapk signaling for", "signaling for 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type", ".

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type", "mouse models.

type 2a", "models.

type 2a disease.", "2a disease. epm2a", "laforin associated", "associated with cytosolic", "with cytosolic glycogen", "cytosolic glycogen granules", "granules normally", "normally catalyzes the", "catalyzes the removal", "the removal of", "removal of the", "of the phosphate", "the phosphate groups", "phosphate groups added", "groups added rarely", "added rarely but", "rarely but consistently", "but consistently to", "consistently to growing", "to growing glycogen", "growing glycogen molecules", "molecules tagliabracci", "tagliabracci et al.", "al. 2011 .", "2011 . defects", ". defects in", "defects in this", "in this catalytic", "this catalytic activity", "catalytic activity lead", "activity lead to", "lead to the", "to the formation", "formation of phosphorylated", "of phosphorylated glycogen", "phosphorylated glycogen molecules", "glycogen molecules that", "molecules that are", "that are insoluble", "are insoluble and", "insoluble and that", "and that show", "that show abnormal", "show abnormal branching", "abnormal branching patterns", "patterns minassian", "minassian et al.", "et al. 1998", "1998 serratosa", "serratosa et al.", "et al. 1999", "1999 tagliabracci", "al. 2011 .

type", "2011 .

type 2b", ".

type 2b disease.", "2b disease. nhlrc1", "malin normally", "normally mediates polyubiquitination", "mediates polyubiquitination of", "polyubiquitination of epm2a", "ppp1r3c ptg", "ptg . the", ". the two", "the two polyubiquitinated", "two polyubiquitinated proteins", "polyubiquitinated proteins are", "proteins are targeted", "are targeted for", "targeted for proteasome", "for proteasome mediated", "proteasome mediated degradation", "degradation leaving", "leaving a glycogen", "a glycogen glycogenin", "glycogen glycogenin particle", "glycogenin particle associated", "particle associated with", "associated with glycogen", "with glycogen synthase.", "glycogen synthase. in", "synthase. in the", "in the absence", "the absence of", "absence of nhlrc1", "of nhlrc1 activity", "activity epm2a", "epm2a and ppp1r3c", "and ppp1r3c proteins", "ppp1r3c proteins appear", "proteins appear to", "appear to persist", "formation of abnormal", "abnormal stable", "stable glycogen granules", "granules lafora", "chan et al.", "et al. 2003", "2003 gentry", "gentry et al.", "et al. 2005", "al. 2005 .", "2005 . in", ". in nhlrc1", "in nhlrc1 knockout", "nhlrc1 knockout mice", "knockout mice ppp1r3c", "mice ppp1r3c levels", "ppp1r3c levels are", "levels are unchanged", "are unchanged rather", "unchanged rather than", "rather than increased", "increased suggesting", "suggesting that nhlrc1", "that nhlrc1 does", "nhlrc1 does not", "does not target", "not target ppp1r3c", "target ppp1r3c for", "ppp1r3c for degradation.", "degradation. however", "however epm2a", "epm2a protein levels", "protein levels are", "levels are increased", "are increased in", "increased in this", "in this knockout", "this knockout consistent", "knockout consistent with", "consistent with nhlrc1's", "with nhlrc1's proposed", "nhlrc1's proposed role", "role depaoli", "depaoli roach et", "et al. 2010", "al. 2010 .", "lafora disease is a", "disease is a progressive", "is a progressive neurodegenerative", "a progressive neurodegenerative disorder", "progressive neurodegenerative disorder with", "neurodegenerative disorder with onset", "disorder with onset typically", "with onset typically late", "onset typically late in", "typically late in childhood", "in childhood characterized", "childhood characterized by", "characterized by seizures and", "by seizures and progressive", "seizures and progressive neurological", "and progressive neurological deterioration", "progressive neurological deterioration and", "neurological deterioration and death", "deterioration and death within", "and death within ten", "death within ten years", "within ten years of", "ten years of onset.", "years of onset. recessive", "of onset. recessive mutations", "onset. recessive mutations in", "recessive mutations in epm2a", "in epm2a laforin", "laforin and nhlrc1", "and nhlrc1 malin", "malin have been", "have been identified as", "been identified as causes", "identified as causes of", "as causes of the", "causes of the disease.", "of the disease. the", "the disease. the disease", "disease. the disease is", "the disease is classified", "disease is classified here", "is classified here as", "classified here as one", "here as one of", "as one of glycogen", "one of glycogen storage", "of glycogen storage as", "glycogen storage as epm2a", "as epm2a laforin", "malin regulate normal", "regulate normal glycogen turnover", "normal glycogen turnover and", "glycogen turnover and defects", "turnover and defects in", "and defects in either", "defects in either protein", "in either protein are", "either protein are associated", "protein are associated with", "are associated with the", "associated with the formation", "with the formation of", "the formation of lafora", "formation of lafora bodies", "lafora bodies accumulations", "bodies accumulations of", "of abnormal insoluble", "abnormal insoluble glycogen", "insoluble glycogen molecules in", "glycogen molecules in tissues", "molecules in tissues including", "tissues including brain", "liver and heart", "and heart ramachandran", "heart ramachandran et", "ramachandran et al. 2009", "al. 2009 roach", "2009 roach et", "roach et al. 2012", "et al. 2012 .", "al. 2012 . consistent", "2012 . consistent with", ". consistent with a", "consistent with a central", "with a central role", "a central role for", "central role for glycogen", "role for glycogen accumulation", "for glycogen accumulation in", "glycogen accumulation in the", "accumulation in the disease", "the disease reduced", "reduced turnbull et", "turnbull et al. 2011", "al. 2011 or", "2011 or absent", "or absent pederson", "absent pederson et", "pederson et al. 2013", "al. 2013 glycogen", "2013 glycogen synthase", "glycogen synthase activity prevents", "synthase activity prevents lafora", "activity prevents lafora disease", "prevents lafora disease in", "lafora disease in mouse", "disease in mouse models.

type", "in mouse models.

type 2a", "mouse models.

type 2a disease.", "models.

type 2a disease. epm2a", "disease. epm2a laforin", "laforin associated with", "associated with cytosolic glycogen", "with cytosolic glycogen granules", "glycogen granules normally", "granules normally catalyzes", "normally catalyzes the removal", "catalyzes the removal of", "the removal of the", "removal of the phosphate", "of the phosphate groups", "the phosphate groups added", "phosphate groups added rarely", "groups added rarely but", "added rarely but consistently", "rarely but consistently to", "but consistently to growing", "consistently to growing glycogen", "to growing glycogen molecules", "glycogen molecules tagliabracci", "molecules tagliabracci et", "tagliabracci et al. 2011", "et al. 2011 .", "al. 2011 . defects", "2011 . defects in", ". defects in this", "defects in this catalytic", "in this catalytic activity", "this catalytic activity lead", "catalytic activity lead to", "activity lead to the", "lead to the formation", "to the formation of", "the formation of phosphorylated", "formation of phosphorylated glycogen", "of phosphorylated glycogen molecules", "phosphorylated glycogen molecules that", "glycogen molecules that are", "molecules that are insoluble", "that are insoluble and", "are insoluble and that", "insoluble and that show", "and that show abnormal", "that show abnormal branching", "show abnormal branching patterns", "branching patterns minassian", "patterns minassian et", "minassian et al. 1998", "al. 1998 serratosa", "1998 serratosa et", "serratosa et al. 1999", "al. 1999 tagliabracci", "1999 tagliabracci et", "et al. 2011 .

type", "al. 2011 .

type 2b", "2011 .

type 2b disease.", ".

type 2b disease. nhlrc1", "disease. nhlrc1 malin", "malin normally mediates", "normally mediates polyubiquitination of", "mediates polyubiquitination of epm2a", "of epm2a laforin", "laforin and ppp1r3c", "and ppp1r3c ptg", "ppp1r3c ptg .", "ptg . the two", ". the two polyubiquitinated", "the two polyubiquitinated proteins", "two polyubiquitinated proteins are", "polyubiquitinated proteins are targeted", "proteins are targeted for", "are targeted for proteasome", "targeted for proteasome mediated", "for proteasome mediated degradation", "mediated degradation leaving", "degradation leaving a", "leaving a glycogen glycogenin", "a glycogen glycogenin particle", "glycogen glycogenin particle associated", "glycogenin particle associated with", "particle associated with glycogen", "associated with glycogen synthase.", "with glycogen synthase. in", "glycogen synthase. in the", "synthase. in the absence", "in the absence of", "the absence of nhlrc1", "absence of nhlrc1 activity", "nhlrc1 activity epm2a", "activity epm2a and", "epm2a and ppp1r3c proteins", "and ppp1r3c proteins appear", "ppp1r3c proteins appear to", "proteins appear to persist", "persist associated", "the formation of abnormal", "of abnormal stable", "abnormal stable glycogen", "glycogen granules lafora", "granules lafora bodies", "bodies chan", "chan et al. 2003", "al. 2003 gentry", "2003 gentry et", "gentry et al. 2005", "et al. 2005 .", "al. 2005 . in", "2005 . in nhlrc1", ". in nhlrc1 knockout", "in nhlrc1 knockout mice", "nhlrc1 knockout mice ppp1r3c", "knockout mice ppp1r3c levels", "mice ppp1r3c levels are", "ppp1r3c levels are unchanged", "levels are unchanged rather", "are unchanged rather than", "unchanged rather than increased", "than increased suggesting", "increased suggesting that", "suggesting that nhlrc1 does", "that nhlrc1 does not", "nhlrc1 does not target", "does not target ppp1r3c", "not target ppp1r3c for", "target ppp1r3c for degradation.", "for degradation. however", "however epm2a protein", "epm2a protein levels are", "protein levels are increased", "levels are increased in", "are increased in this", "increased in this knockout", "in this knockout consistent", "this knockout consistent with", "knockout consistent with nhlrc1's", "consistent with nhlrc1's proposed", "with nhlrc1's proposed role", "proposed role depaoli", "role depaoli roach", "depaoli roach et al.", "roach et al. 2010", "et al. 2010 .", "lafora disease is a progressive", "disease is a progressive neurodegenerative", "is a progressive neurodegenerative disorder", "a progressive neurodegenerative disorder with", "progressive neurodegenerative disorder with onset", "neurodegenerative disorder with onset typically", "disorder with onset typically late", "with onset typically late in", "onset typically late in childhood", "late in childhood characterized", "in childhood characterized by", "childhood characterized by seizures", "characterized by seizures and progressive", "by seizures and progressive neurological", "seizures and progressive neurological deterioration", "and progressive neurological deterioration and", "progressive neurological deterioration and death", "neurological deterioration and death within", "deterioration and death within ten", "and death within ten years", "death within ten years of", "within ten years of onset.", "ten years of onset. recessive", "years of onset. recessive mutations", "of onset. recessive mutations in", "onset. recessive mutations in epm2a", "mutations in epm2a laforin", "epm2a laforin and", "nhlrc1 malin have", "malin have been identified", "have been identified as causes", "been identified as causes of", "identified as causes of the", "as causes of the disease.", "causes of the disease. the", "of the disease. the disease", "the disease. the disease is", "disease. the disease is classified", "the disease is classified here", "disease is classified here as", "is classified here as one", "classified here as one of", "here as one of glycogen", "as one of glycogen storage", "one of glycogen storage as", "of glycogen storage as epm2a", "storage as epm2a laforin", "nhlrc1 malin regulate", "malin regulate normal glycogen", "regulate normal glycogen turnover and", "normal glycogen turnover and defects", "glycogen turnover and defects in", "turnover and defects in either", "and defects in either protein", "defects in either protein are", "in either protein are associated", "either protein are associated with", "protein are associated with the", "are associated with the formation", "associated with the formation of", "with the formation of lafora", "the formation of lafora bodies", "of lafora bodies accumulations", "lafora bodies accumulations of", "bodies accumulations of abnormal", "accumulations of abnormal insoluble", "of abnormal insoluble glycogen", "abnormal insoluble glycogen molecules", "insoluble glycogen molecules in tissues", "glycogen molecules in tissues including", "in tissues including brain", "including brain muscle", "brain muscle liver", "muscle liver and", "and heart ramachandran et", "heart ramachandran et al.", "et al. 2009 roach", "al. 2009 roach et", "2009 roach et al.", "roach et al. 2012 .", "et al. 2012 . consistent", "al. 2012 . consistent with", "2012 . consistent with a", ". consistent with a central", "consistent with a central role", "with a central role for", "a central role for glycogen", "central role for glycogen accumulation", "role for glycogen accumulation in", "for glycogen accumulation in the", "glycogen accumulation in the disease", "in the disease reduced", "disease reduced turnbull", "reduced turnbull et al.", "et al. 2011 or", "al. 2011 or absent", "or absent pederson et", "absent pederson et al.", "et al. 2013 glycogen", "al. 2013 glycogen synthase", "2013 glycogen synthase activity", "glycogen synthase activity prevents lafora", "synthase activity prevents lafora disease", "activity prevents lafora disease in", "prevents lafora disease in mouse", "lafora disease in mouse models.

type", "disease in mouse models.

type 2a", "in mouse models.

type 2a disease.", "mouse models.

type 2a disease. epm2a", "2a disease. epm2a laforin", "epm2a laforin associated", "laforin associated with cytosolic", "associated with cytosolic glycogen granules", "cytosolic glycogen granules normally", "glycogen granules normally catalyzes", "granules normally catalyzes the", "normally catalyzes the removal of", "catalyzes the removal of the", "the removal of the phosphate", "removal of the phosphate groups", "of the phosphate groups added", "the phosphate groups added rarely", "phosphate groups added rarely but", "groups added rarely but consistently", "added rarely but consistently to", "rarely but consistently to growing", "but consistently to growing glycogen", "consistently to growing glycogen molecules", "growing glycogen molecules tagliabracci", "glycogen molecules tagliabracci et", "molecules tagliabracci et al.", "tagliabracci et al. 2011 .", "et al. 2011 . defects", "al. 2011 . defects in", "2011 . defects in this", ". defects in this catalytic", "defects in this catalytic activity", "in this catalytic activity lead", "this catalytic activity lead to", "catalytic activity lead to the", "activity lead to the formation", "lead to the formation of", "to the formation of phosphorylated", "the formation of phosphorylated glycogen", "formation of phosphorylated glycogen molecules", "of phosphorylated glycogen molecules that", "phosphorylated glycogen molecules that are", "glycogen molecules that are insoluble", "molecules that are insoluble and", "that are insoluble and that", "are insoluble and that show", "insoluble and that show abnormal", "and that show abnormal branching", "that show abnormal branching patterns", "abnormal branching patterns minassian", "branching patterns minassian et", "patterns minassian et al.", "et al. 1998 serratosa", "al. 1998 serratosa et", "1998 serratosa et al.", "et al. 1999 tagliabracci", "al. 1999 tagliabracci et", "1999 tagliabracci et al.", "tagliabracci et al. 2011 .

type", "et al. 2011 .

type 2b", "al. 2011 .

type 2b disease.", "2011 .

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in the", "glycogen synthase. in the absence", "synthase. in the absence of", "in the absence of nhlrc1", "the absence of nhlrc1 activity", "of nhlrc1 activity epm2a", "nhlrc1 activity epm2a and", "activity epm2a and ppp1r3c", "epm2a and ppp1r3c proteins appear", "and ppp1r3c proteins appear to", "ppp1r3c proteins appear to persist", "to persist associated", "persist associated with", "with the formation of abnormal", "formation of abnormal stable", "of abnormal stable glycogen", "abnormal stable glycogen granules", "stable glycogen granules lafora", "glycogen granules lafora bodies", "lafora bodies chan", "bodies chan et", "et al. 2003 gentry", "al. 2003 gentry et", "2003 gentry et al.", "gentry et al. 2005 .", "et al. 2005 . in", "al. 2005 . in nhlrc1", "2005 . in nhlrc1 knockout", ". in nhlrc1 knockout mice", "in nhlrc1 knockout mice ppp1r3c", "nhlrc1 knockout mice ppp1r3c levels", "knockout mice ppp1r3c levels are", "mice ppp1r3c levels are unchanged", "ppp1r3c levels are unchanged 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c terminal", "cytosolic c terminal region.", "c terminal region. the", "terminal region. the phosphorylation", "region. the phosphorylation causes", "the phosphorylation causes a", "phosphorylation causes a conformational", "causes a conformational change", "a conformational change that", "conformational change that allows", "change that allows the", "that allows the dimer", "allows the dimer to", "the dimer to bind", "dimer to bind adp", "bind adp causing", "adp causing a", "causing a further conformational", "a further conformational change", "further conformational change to", "conformational change to yield", "change to yield back", "to yield back to", "yield back to back", "back to back pairing", "to back pairing of", "back pairing of the", "pairing of the cytosolic", "of the cytosolic c", "cytosolic c terminal regions", "c terminal regions of", "terminal regions of ire1", "regions of ire1 alpha.", "of ire1 alpha. the", "ire1 alpha. the fully", "alpha. the fully paired", "the fully paired ire1", "fully paired ire1 alpha", "paired ire1 alpha homodimer", "ire1 alpha homodimer has", "alpha homodimer has endoribonuclease", "homodimer has endoribonuclease activity", "has endoribonuclease activity and", "endoribonuclease activity and cleaves", "activity and cleaves the", "and cleaves the mrna", "cleaves the mrna encoding", "the mrna encoding xbp", "mrna encoding xbp 1.", "encoding xbp 1. a", "xbp 1. a 26", "1. a 26 residue", "a 26 residue polyribonucleotide", "26 residue polyribonucleotide is", "residue polyribonucleotide is released", "polyribonucleotide is released and", "is released and the", "released and the 5'", "and the 5' and", "the 5' and 3'", "5' and 3' fragments", "and 3' fragments of", "3' fragments of the", "fragments of the original", "of the original xbp", "the original xbp 1", "original xbp 1 mrna", "xbp 1 mrna are", "1 mrna are rejoined.", "mrna are rejoined. the", "are rejoined. the spliced", "rejoined. the spliced xbp", "the spliced xbp 1", 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also", "homodimer can also cleave", "can also cleave specific", "also cleave specific subsets", "cleave specific subsets of", "specific subsets of mrnas", "of mrnas including", "mrnas including the", "the insulin ins", "ins mrna in", "mrna in pancreatic beta", "in pancreatic beta cells.", "ire1 alpha is a single", "alpha is a single pass", "is a single pass transmembrane", "a single pass transmembrane protein", "single pass transmembrane protein that", "pass transmembrane protein that resides", "transmembrane protein that resides in", "protein that resides in the", "that resides in the endoplasmic", "resides in the endoplasmic reticulum", "the endoplasmic reticulum er", "reticulum er membrane.", "er membrane. the c", "membrane. the c terminus of", "the c terminus of ire1", "c terminus of ire1 alpha", "terminus of ire1 alpha is", "of ire1 alpha is located", "ire1 alpha is located in", "alpha is located in the", "is located in the cytosol", "in the cytosol the", "the cytosol the n", "cytosol the n terminus", "the n terminus is located", "n terminus is located in", "terminus is located in the", "is located in the er", "located in the er lumen.", "in the er lumen. in", "the er lumen. in unstressed", "er lumen. in unstressed cells", "lumen. in unstressed cells ire1", "in unstressed cells ire1 alpha", "unstressed cells ire1 alpha exists", "cells ire1 alpha exists in", "ire1 alpha exists in an", "alpha exists in an inactive", "exists in an inactive heterodimeric", "in an inactive heterodimeric complex", "an inactive heterodimeric complex with", "inactive heterodimeric complex with bip", "heterodimeric complex with bip such", "complex with bip such that", "with bip such that bip", "bip such that bip in", "such that bip in the", "that bip in the er", "bip in the er lumen", "in the er lumen binds", "the er lumen binds the", "er lumen binds the n", "lumen binds the n terminal", "binds the n terminal region", "the n terminal region of", "n terminal region of ire1", "terminal region of ire1 alpha.", "region of ire1 alpha. upon", "of ire1 alpha. upon accumulation", "ire1 alpha. upon accumulation of", "alpha. upon accumulation of unfolded", "upon accumulation of unfolded proteins", "accumulation of unfolded proteins in", "of unfolded proteins in the", "unfolded proteins in the er", "in the er bip", "the er bip binds", "er bip binds the", "bip binds the unfolded protein", "binds the unfolded protein and", "the unfolded protein and the", "unfolded protein and the ire1", "protein and the ire1 alpha:bip", "and the ire1 alpha:bip complex", "the ire1 alpha:bip complex dissociates.", "ire1 alpha:bip complex dissociates. the", "alpha:bip complex dissociates. the dissociated", "complex dissociates. the dissociated ire1", "dissociates. the dissociated ire1 alpha", "the dissociated ire1 alpha then", "dissociated ire1 alpha then forms", "ire1 alpha then forms homodimers.", "alpha then forms homodimers. initially", "then forms homodimers. initially the", "forms homodimers. initially the luminal", "homodimers. initially the luminal n", "initially the luminal n terminal", "the luminal n terminal regions", "luminal n terminal regions pair.", "n terminal regions pair. this", "terminal regions pair. this is", "regions pair. this is followed", "pair. this is followed by", "this is followed by trans", "is followed by trans autophosphorylation", "followed by trans autophosphorylation of", "by trans autophosphorylation of ire1", "trans autophosphorylation of ire1 alpha", "autophosphorylation of ire1 alpha at", "of ire1 alpha at ser724", "ire1 alpha at ser724 in", "alpha at ser724 in the", "at ser724 in the cytosolic", "ser724 in the cytosolic c", "in the cytosolic c terminal", "the cytosolic c terminal region.", "cytosolic c terminal region. the", "c terminal region. the phosphorylation", "terminal region. the phosphorylation causes", "region. the phosphorylation causes a", "the phosphorylation causes a conformational", "phosphorylation causes a conformational change", "causes a conformational change that", "a conformational change that allows", "conformational change that allows the", "change that allows the dimer", "that allows the dimer to", "allows the dimer to bind", "the dimer to bind adp", "to bind adp causing", "bind adp causing a", "adp causing a further", "causing a further conformational change", "a further conformational change to", "further conformational change to yield", "conformational change to yield back", "change to yield back to", "to yield back to back", "yield back to back pairing", "back to back pairing of", "to back pairing of the", "back pairing of the cytosolic", "pairing of the cytosolic c", "of the cytosolic c terminal", "the cytosolic c terminal regions", "cytosolic c terminal regions of", "c terminal regions of ire1", "terminal regions of ire1 alpha.", "regions of ire1 alpha. the", "of ire1 alpha. the fully", "ire1 alpha. the fully paired", "alpha. the fully paired ire1", "the fully paired ire1 alpha", "fully paired ire1 alpha homodimer", "paired ire1 alpha homodimer has", "ire1 alpha homodimer has endoribonuclease", "alpha homodimer has endoribonuclease activity", "homodimer has endoribonuclease activity and", "has endoribonuclease activity and cleaves", "endoribonuclease activity and cleaves the", "activity and cleaves the mrna", "and cleaves the mrna encoding", "cleaves the mrna encoding xbp", "the mrna encoding xbp 1.", "mrna encoding xbp 1. a", "encoding xbp 1. a 26", "xbp 1. a 26 residue", "1. a 26 residue polyribonucleotide", "a 26 residue polyribonucleotide is", "26 residue polyribonucleotide is released", "residue polyribonucleotide is released and", "polyribonucleotide is released and the", "is released and the 5'", "released and the 5' and", "and the 5' and 3'", "the 5' and 3' fragments", "5' and 3' fragments of", "and 3' fragments of the", "3' fragments of the original", "fragments of the original xbp", "of the original xbp 1", "the original xbp 1 mrna", "original xbp 1 mrna are", "xbp 1 mrna are rejoined.", "1 mrna are rejoined. the", "mrna are rejoined. the spliced", "are rejoined. the spliced xbp", "rejoined. the spliced xbp 1", "the spliced xbp 1 message", "spliced xbp 1 message encodes", "xbp 1 message encodes xbp", "1 message encodes xbp 1", "encodes xbp 1 s", "s a potent", "a potent activator of transcription.", "potent activator of transcription. xbp", "activator of transcription. xbp 1", "transcription. xbp 1 s", "1 s together", "s together with the", "together with the ubiquitous transcription", "with the ubiquitous transcription factor", "the ubiquitous transcription factor nf", "ubiquitous transcription factor nf y", "transcription factor nf y bind", "factor nf y bind the", "nf y bind the er", "y bind the er stress", "bind the er stress responsive", "the er stress responsive element", "stress responsive element erse", "element erse in", "erse in a number", "in a number of genes", "a number of genes encoding", "number of genes encoding chaperones.", "of genes encoding chaperones. recent", "genes encoding chaperones. recent data", "encoding chaperones. recent data suggest", "chaperones. recent data suggest that", "recent data suggest that the", "data suggest that the ire1", "suggest that the ire1 alpha", "that the ire1 alpha homodimer", "the ire1 alpha homodimer can", "ire1 alpha homodimer can also", "alpha homodimer can also cleave", "homodimer can also cleave specific", "can also cleave specific subsets", "also cleave specific subsets of", "cleave specific subsets of mrnas", "subsets of mrnas including", "of mrnas including the", "mrnas including the insulin", "including the insulin ins", "insulin ins mrna", "ins mrna in pancreatic", "mrna in pancreatic beta cells." ] }, { "record_id": "GLY_000594_1_945", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "383280", "r hsa", "hsa 383280", "r hsa 383280" ] }, { "record_id": "GLY_000594_1_945", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nuclear receptor", "receptor transcription", "transcription pathway", "nuclear receptor transcription", "receptor transcription pathway", "nuclear receptor transcription pathway", "a classic", "classic example", "example of", "of bifunctional", "bifunctional transcription", "transcription factors", "factors is", "is the", "the family", "family of", "of nuclear", "these are", "are dna", "dna binding", "binding transcription", "factors that", "that bind", "bind certain", "certain hormones", "and other", "other small", "diffusible signaling", "signaling molecules.", "the non", "non liganded", "liganded nrs", "nrs recruit", "recruit specific", "specific corepressor", "corepressor complexes", "complexes of", "of the", "the ncor/smrt", "ncor/smrt type", "to mediate", "mediate transcriptional", "transcriptional repression", "repression of", "the target", "target genes", "genes to", "to which", "which they", "they are", "are bound.", "during signaling", "ligand binding", "binding to", "to a", "a specific", "specific domain", "domain the", "the nr", "nr proteins", "proteins induces", "induces a", "a conformational", "conformational change", "change that", "that results", "results in", "in the", "the exchange", "exchange of", "the associated", "associated cor", "cor complex", "and its", "its replacement", "replacement by", "by a", "specific coactivator", "coactivator complex", "complex of", "the trap", "trap /", "/ drip", "drip /", "/ mediator", "mediator type.", "these coactivator", "coactivator complexes", "complexes typically", "typically nucleate", "nucleate around", "around a", "a med1", "med1 coactivator", "coactivator protein", "protein that", "that is", "is directly", "directly bound", "bound to", "to the", "nr transcription", "transcription factor.

a", "factor.

a general", "general feature", "feature of", "the 49", "49 human", "human nr", "proteins is", "is that", "that in", "the unliganded", "unliganded state", "they each", "each bind", "bind directly", "directly to", "to an", "an ncor", "ncor corepressor", "corepressor protein", "either ncor1", "ncor1 or", "or ncor2", "ncor2 was", "was previously", "previously named", "named \\smrt\\", "\\smrt\\ .", "this ncor", "ncor protein", "protein nucleates", "nucleates the", "the assembly", "assembly of", "of additional", "corepressor proteins", "depending on", "on the", "the cell", "cell and", "and dna", "dna context.", "nr ncor", "ncor interaction", "interaction is", "is mediated", "mediated by", "specific protein", "protein interaction", "interaction domain", "present in", "the nrs", "nrs that", "that binds", "binds to", "to specific", "specific cognate", "cognate pid", "pid s", "the ncor", "ncor proteins.", "the human", "human nrs", "nrs each", "each take", "take part", "part in", "in an", "an nr", "ncor binding", "binding reaction", "reaction in", "the absence", "absence of", "of binding", "binding by", "by their", "their ligand.

a", "ligand.

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"human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "388844", "r hsa", "hsa 388844", "r hsa 388844" ] }, { "record_id": "GLY_000594_1_947", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "receptor type", "type tyrosine", "tyrosine protein", "protein phosphatases", "receptor type tyrosine", "type tyrosine protein", "tyrosine protein phosphatases", "receptor type tyrosine protein", "type tyrosine protein phosphatases", "receptor type tyrosine protein phosphatases", "like neurexins", "receptor like", "like protein", "protein tyrosine", "tyrosine phosphatases", "make trans", "trans synaptic", "synaptic adhesion", "adhesion complexes", "complexes with", "with multiple", "multiple postsynaptic", "postsynaptic binding", "binding partners", "partners to", "to regulate", "regulate synapse", "synapse organization.", "organization. the", "the type", "type iia", "iia rptps", "rptps include", "include three", "three members", "protein phosphatase", "phosphatase f", "sometimes referred", "referred to", "to as", "as leukocyte", "leukocyte common", "common antigen", "antigen related", "phosphatase sigma", "and receptor", "phosphatase delta", "ptprd .", ". these", "these proteins", "proteins contain", "contain typical", "typical cell", "cell adhesion", "adhesion immunoglobulin", "immunoglobulin like", "and fibronectin", "fibronectin iii", "suggesting the", "the involvement", "involvement of", "of rptps", "rptps in", "in cell", "cell cell", "cell and", "and cell", "cell matrix", "matrix interactions.", "interactions. to", "to date", "six different", "different types", "types of", "of postsynaptic", "postsynaptic organizers", "organizers for", "for type", "rptps have", "have been", "been reported:", "reported: interleukin", "interleukin 1", "1 receptor", "receptor accessory", "accessory protein", "il 1racp", "yoshida et", "et al.", "al. 2012", "1racp like", "like 1", "al. 2011", "neurotrophin receptor", 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interactions. to", "interactions. to date", "date six", "six different types", "different types of", "types of postsynaptic", "of postsynaptic organizers", "postsynaptic organizers for", "organizers for type", "for type iia", "iia rptps have", "rptps have been", "have been reported:", "been reported: interleukin", "reported: interleukin 1", "interleukin 1 receptor", "1 receptor accessory", "receptor accessory protein", "protein il1rap", "il1rap il", "yoshida et al.", "et al. 2012", "il 1racp like", "1racp like 1", "1 il1rapl1", "et al. 2011", "neurotrophin receptor tyrosine", "receptor tyrosine kinase", "tyrosine kinase 3", "3 ntrk3", "ntrk3 trkc", "takahashi et al.", "leucine rich repeat", "rich repeat containing", "repeat containing protein", "containing protein 4b", "4b lrrc4b", "lrrc4b netrin", "netrin g ligand", "g ligand 3", "3 ngl", "woo et al.", "et al. 2009", "2009 kwon", "kwon et al.", "et al. 2010", "slit and", "and trk like", "like slitrk", "slitrk family", "proteins takahashi", "2012 yim", "yim et al.", "et al. 2013", "2013 yamagata", "yamagata et al.", "et al. 2015", "2015 and", "and the liprins", "liprins serra", "serra pag\u00e8s et", "pag\u00e8s et al.", "et al. 1998", "1998 dunah", "dunah et al.", "et al. 2005", "al. 2005 .", "like neurexins receptor", "neurexins receptor like", "receptor like protein tyrosine", "like protein tyrosine phosphatases", "tyrosine phosphatases rptps", "rptps make trans", "make trans synaptic adhesion", "trans synaptic adhesion complexes", "synaptic adhesion complexes with", "adhesion complexes with multiple", "complexes with multiple postsynaptic", "with multiple postsynaptic binding", "multiple postsynaptic binding partners", "postsynaptic binding partners to", "binding partners to regulate", "partners to regulate synapse", "to regulate synapse organization.", "regulate synapse organization. the", "synapse organization. the type", "organization. the type iia", "the type iia rptps", "type iia rptps include", "iia rptps include three", "rptps include three members", "three members receptor", "members receptor type", "type tyrosine protein phosphatase", "tyrosine protein phosphatase f", "phosphatase f ptprf", "ptprf sometimes referred", "sometimes referred to as", "referred to as leukocyte", "to as leukocyte common", "as leukocyte common antigen", "leukocyte common antigen related", "antigen related lar", "lar receptor", "tyrosine protein phosphatase sigma", "phosphatase sigma ptprs", "ptprs and receptor", "and receptor type tyrosine", "tyrosine protein phosphatase delta", "phosphatase delta ptprd", "delta ptprd .", "ptprd . these proteins", ". these proteins contain", "these proteins contain typical", "proteins contain typical cell", "contain typical cell adhesion", "typical cell adhesion immunoglobulin", "cell adhesion immunoglobulin like", "immunoglobulin like ig", "ig and fibronectin", "fibronectin iii fniii", "domains suggesting the", "suggesting the involvement of", "the involvement of rptps", "involvement of rptps in", "of rptps in cell", "rptps in cell cell", "in cell cell and", "cell cell and cell", "cell and cell matrix", "and cell matrix interactions.", "cell matrix interactions. to", "matrix interactions. to date", "to date six", "date six different", "six different types of", "different types of postsynaptic", "types of postsynaptic organizers", "of postsynaptic organizers for", "postsynaptic organizers for type", "organizers for type iia", "for type iia rptps", "type iia rptps have", "iia rptps have been", "rptps have been reported:", "have been reported: interleukin", "been reported: interleukin 1", "reported: interleukin 1 receptor", "interleukin 1 receptor accessory", "1 receptor accessory protein", "accessory protein il1rap", "il1rap il 1racp", "1racp yoshida", "yoshida et al. 2012", "2012 il", "il 1racp like 1", "like 1 il1rapl1", "il1rapl1 yoshida", "yoshida et al. 2011", "2011 neurotrophin", "neurotrophin receptor tyrosine kinase", "receptor tyrosine kinase 3", "kinase 3 ntrk3", "trkc takahashi", "takahashi et al. 2011", "2011 leucine", "leucine rich repeat containing", "rich repeat containing protein", "repeat containing protein 4b", "protein 4b lrrc4b", "lrrc4b netrin g", "netrin g ligand 3", "ligand 3 ngl", "3 ngl 3", "3 woo", "woo et al. 2009", "al. 2009 kwon", "2009 kwon et", "kwon et al. 2010", "2010 the", "the slit and", "slit and trk", "trk like slitrk", "slitrk family proteins", "family proteins takahashi", "proteins takahashi et", "takahashi et al. 2012", "al. 2012 yim", "2012 yim et", "yim et al. 2013", "al. 2013 yamagata", "2013 yamagata et", "yamagata et al. 2015", "al. 2015 and", "2015 and the", "the liprins serra", "liprins serra pag\u00e8s", "serra pag\u00e8s et al.", "pag\u00e8s et al. 1998", "al. 1998 dunah", "1998 dunah et", "dunah et al. 2005", "et al. 2005 .", "like neurexins receptor like", "neurexins receptor like protein", "receptor like protein tyrosine phosphatases", "protein tyrosine phosphatases rptps", "phosphatases rptps make", "rptps make trans synaptic", "make trans synaptic adhesion complexes", "trans synaptic adhesion complexes with", "synaptic adhesion complexes with multiple", "adhesion complexes with multiple postsynaptic", "complexes with multiple postsynaptic binding", "with multiple postsynaptic binding partners", "multiple postsynaptic binding partners to", "postsynaptic binding partners to regulate", "binding partners to regulate synapse", "partners to regulate synapse organization.", "to regulate synapse organization. the", "regulate synapse organization. the type", "synapse organization. the type iia", "organization. the type iia rptps", "the type iia rptps include", "type iia rptps include three", "iia rptps include three members", "include three members receptor", "three members receptor type", "members receptor type tyrosine", "receptor type tyrosine protein phosphatase", "type tyrosine protein phosphatase f", "protein phosphatase f ptprf", "f ptprf sometimes", "ptprf sometimes referred to", "sometimes referred to as leukocyte", "referred to as leukocyte common", "to as leukocyte common antigen", "as leukocyte common antigen related", "common antigen related lar", "lar receptor type", "type tyrosine protein phosphatase sigma", "protein phosphatase sigma ptprs", "sigma ptprs and", "ptprs and receptor type", "and receptor type tyrosine protein", "type tyrosine protein phosphatase delta", "protein phosphatase delta ptprd", "phosphatase delta ptprd .", "delta ptprd . these", "ptprd . these proteins contain", ". these proteins contain typical", "these proteins contain typical cell", "proteins contain typical cell adhesion", "contain typical cell adhesion immunoglobulin", "typical cell adhesion immunoglobulin like", "adhesion immunoglobulin like ig", "like ig and", "ig and fibronectin iii", "and fibronectin iii fniii", "iii fniii domains", "fniii domains suggesting", "domains suggesting the involvement", "suggesting the involvement of rptps", "the involvement of rptps in", "involvement of rptps in cell", "of rptps in cell cell", "rptps in cell cell and", "in cell cell and cell", "cell cell and cell matrix", "cell and cell matrix interactions.", "and cell matrix interactions. to", "cell matrix interactions. to date", "interactions. to date six", "to date six different", "date six different types", "six different types of postsynaptic", "different types of postsynaptic organizers", "types of postsynaptic organizers for", "of postsynaptic organizers for type", "postsynaptic organizers for type iia", "organizers for type iia rptps", "for type iia rptps have", "type iia rptps have been", "iia rptps have been reported:", "rptps have been reported: interleukin", "have been reported: interleukin 1", "been reported: interleukin 1 receptor", "reported: interleukin 1 receptor accessory", "interleukin 1 receptor accessory protein", "receptor accessory protein il1rap", "protein il1rap il", "il 1racp yoshida", "1racp yoshida et", "al. 2012 il", "2012 il 1racp", "1racp like 1 il1rapl1", "il1rapl1 yoshida et", "al. 2011 neurotrophin", "2011 neurotrophin receptor", "neurotrophin receptor tyrosine kinase 3", "tyrosine kinase 3 ntrk3", "3 ntrk3 trkc", "trkc takahashi et", "al. 2011 leucine", "2011 leucine rich", "leucine rich repeat containing protein", "rich repeat containing protein 4b", "containing protein 4b lrrc4b", "4b lrrc4b netrin", "lrrc4b netrin g ligand", "g ligand 3 ngl", "ligand 3 ngl 3", "ngl 3 woo", "3 woo et", "et al. 2009 kwon", "al. 2009 kwon et", "2009 kwon et al.", "al. 2010 the", "2010 the slit", "the slit and trk", "slit and trk like", "and trk like slitrk", "like slitrk family", "family proteins takahashi et", "proteins takahashi et al.", "et al. 2012 yim", "al. 2012 yim et", "2012 yim et al.", "et al. 2013 yamagata", "al. 2013 yamagata et", "2013 yamagata et al.", "et al. 2015 and", "al. 2015 and the", "2015 and the liprins", "and the liprins serra", "the liprins serra pag\u00e8s", "liprins serra pag\u00e8s et", "serra pag\u00e8s et al. 1998", "et al. 1998 dunah", "al. 1998 dunah et", "1998 dunah et al.", "dunah et al. 2005 ." ] }, { "record_id": "GLY_000594_1_948", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "389356", "r hsa", "hsa 389356", "r hsa 389356" ] }, { "record_id": "GLY_000594_1_948", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "co stimulation", "stimulation by", "by cd28", "co stimulation by", "stimulation by cd28", "co stimulation by cd28", "cd28 signaling", "signaling plays", "plays a", "a critical", "critical role", "role in", "in shaping", "shaping immune", "immune responses", "responses by", "by ensuring", "ensuring effective", "effective t", "t cell", "cell activation", "activation and", "and enhancing", "enhancing t", "cell survival", "survival and", "and proliferation.", "proliferation. when", "when cd28", "cd28 engages", "engages its", "its ligands", "b7 1", "and b7", "b7 2", "on antigen", "antigen presenting", "presenting cells", "it provides", "provides an", "an essential", "essential secondary", "secondary signal", "signal that", "that complements", "complements t", "cell receptor", "activation. this", "this costimulatory", "costimulatory signal", "signal leads", "leads to", "to the", "the production", "production of", "of interleukin", "interleukin 2", "il 2", "which supports", "supports the", "the clonal", "clonal expansion", "expansion of", "of t", "t cells", "promoting both", "both their", "their proliferation", "proliferation and", "and survival", "survival by", "by initiating", "initiating anti", "anti apoptotic", "apoptotic pathways", "ribot et", "et al.", "al. 2012", "alegre et", "al. 2001", "2001 .", ".

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the", ".

the cytoplasmic", "

the cytoplasmic tail", "cytoplasmic tail of", "tail of cd28", "cd28 upon", "upon ligand binding", "binding undergoes", "undergoes phosphorylation by", "phosphorylation by src", "by src family", "src family kinases", "family kinases like", "kinases like lck", "like lck and", "lck and fyn", "fyn triggering", "triggering downstream signaling", "downstream signaling pathways", "signaling pathways involving", "pathways involving pi3k", "pi3k vav", "1 tec", "tec family kinases", "kinases akt", "akt and", "and other adaptor", "other adaptor proteins", "proteins sharpe", "sharpe & freeman", "& freeman 2002", "2002 chen", "chen & flies", "& flies 2013", "flies 2013 .", "cd28 signaling plays a", "signaling plays a critical", "plays a critical role", "a critical role in", "critical role in shaping", "role in shaping immune", "in shaping immune responses", "shaping immune responses by", "immune responses by ensuring", "responses by ensuring effective", "by ensuring effective t", "ensuring effective t cell", "effective t cell activation", "t cell activation and", "cell activation and enhancing", "activation and enhancing t", "and enhancing t cell", "enhancing t cell survival", "t cell survival and", "cell survival and proliferation.", "survival and proliferation. when", "and proliferation. when cd28", "proliferation. when cd28 engages", "when cd28 engages its", "cd28 engages its ligands", "its ligands b7", "ligands b7 1", "b7 1 cd80", "cd80 and b7", "b7 2 cd86", "cd86 on", "on antigen presenting cells", "presenting cells it", "cells it provides", "it provides an essential", "provides an essential secondary", "an essential secondary signal", "essential secondary signal that", "secondary signal that complements", "signal that complements t", "that complements t cell", "complements t cell receptor", "cell receptor tcr", "tcr activation. this", "activation. this costimulatory signal", "this costimulatory signal leads", "costimulatory signal leads to", "signal leads to the", "leads to the production", "to the production of", "the production of interleukin", "production of interleukin 2", "interleukin 2 il", "2 il 2", "2 which", "which supports the clonal", "supports the clonal expansion", "the clonal expansion of", "clonal expansion of t", "expansion of t cells", "t cells promoting", "cells promoting both", "promoting both their proliferation", "both their proliferation and", "their proliferation and survival", "proliferation and survival by", "and survival by initiating", "survival by initiating anti", "by initiating anti apoptotic", "initiating anti apoptotic pathways", "apoptotic pathways ribot", "pathways ribot et", "ribot et al. 2012", "al. 2012 alegre", "2012 alegre et", "alegre et al. 2001", "et al. 2001 .", "al. 2001 .

the", "2001 .

the cytoplasmic", ".

the cytoplasmic tail", "

the cytoplasmic tail of", "cytoplasmic tail of cd28", "of cd28 upon", "cd28 upon ligand", "ligand binding undergoes", "binding undergoes phosphorylation", "undergoes phosphorylation by src", "phosphorylation by src family", "by src family kinases", "src family kinases like", "family kinases like lck", "kinases like lck and", "like lck and fyn", "and fyn triggering", "fyn triggering downstream", "triggering downstream signaling pathways", "downstream signaling pathways involving", "signaling pathways involving pi3k", "involving pi3k vav", "pi3k vav 1", "vav 1 tec", "1 tec family", "family kinases akt", "akt and other", "and other adaptor proteins", "adaptor proteins sharpe", "proteins sharpe &", "sharpe & freeman 2002", "freeman 2002 chen", "2002 chen &", "chen & flies 2013", "& flies 2013 .", "cd28 signaling plays a critical", "signaling plays a critical role", "plays a critical role in", "a critical role in shaping", "critical role in shaping immune", "role in shaping immune responses", "in shaping immune responses by", "shaping immune responses by ensuring", "immune responses by ensuring effective", "responses by ensuring effective t", "by ensuring effective t cell", "ensuring effective t cell activation", "effective t cell activation and", "t cell activation and enhancing", "cell activation and enhancing t", "activation and enhancing t cell", "and enhancing t cell survival", "enhancing t cell survival and", "t cell survival and proliferation.", "cell survival and proliferation. when", "survival and proliferation. when cd28", "and proliferation. when cd28 engages", "proliferation. when cd28 engages its", "when cd28 engages its ligands", "engages its ligands b7", "its ligands b7 1", "1 cd80 and", "cd80 and b7 2", "and b7 2 cd86", "cd86 on antigen", "antigen presenting cells it", "presenting cells it provides", "cells it provides an", "it provides an essential secondary", "provides an essential secondary signal", "an essential secondary signal that", "essential secondary signal that complements", "secondary signal that complements t", "signal that complements t cell", "that complements t cell receptor", "t cell receptor tcr", "receptor tcr activation.", "tcr activation. this costimulatory", "activation. this costimulatory signal leads", "this costimulatory signal leads to", "costimulatory signal leads to the", "signal leads to the production", "leads to the production of", "to the production of interleukin", "the production of interleukin 2", "of interleukin 2 il", "interleukin 2 il 2", "il 2 which", "2 which supports", "which supports the clonal expansion", "supports the clonal expansion of", "the clonal expansion of t", "clonal expansion of t cells", "of t cells promoting", "t cells promoting both", "cells promoting both their", "promoting both their proliferation and", "both their proliferation and survival", "their proliferation and survival by", "proliferation and survival by initiating", "and survival by initiating anti", "survival by initiating anti apoptotic", "by initiating anti apoptotic pathways", "anti apoptotic pathways ribot", "apoptotic pathways ribot et", "pathways ribot et al.", "et al. 2012 alegre", "al. 2012 alegre et", "2012 alegre et al.", "alegre et al. 2001 .", "et al. 2001 .

the", "al. 2001 .

the cytoplasmic", "2001 .

the cytoplasmic tail", ".

the cytoplasmic tail of", "

the cytoplasmic tail of cd28", "tail of cd28 upon", "of cd28 upon ligand", "cd28 upon ligand binding", "upon ligand binding undergoes", "ligand binding undergoes phosphorylation", "binding undergoes phosphorylation by", "undergoes phosphorylation by src family", "phosphorylation by src family kinases", "by src family kinases like", "src family kinases like lck", "family kinases like lck and", "kinases like lck and fyn", "lck and fyn triggering", "and fyn triggering downstream", "fyn triggering downstream signaling", "triggering downstream signaling pathways involving", "downstream signaling pathways involving pi3k", "pathways involving pi3k vav", "involving pi3k vav 1", "vav 1 tec family", "1 tec family kinases", "tec family kinases akt", "kinases akt and", "akt and other adaptor", "other adaptor proteins sharpe", "adaptor proteins sharpe &", "proteins sharpe & freeman", "& freeman 2002 chen", "freeman 2002 chen &", "2002 chen & flies", "chen & flies 2013 ." ] }, { "record_id": "GLY_000594_1_949", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "389359", "r hsa", "hsa 389359", "r hsa 389359" ] }, { "record_id": "GLY_000594_1_949", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cd28 dependent", "dependent vav1", "vav1 pathway", "cd28 dependent vav1", "dependent vav1 pathway", "cd28 dependent vav1 pathway", "cd28 binds", "binds to", "to several", "several intracellular", "intracellular signaling", "signaling proteins", "including pi3", "pi3 kinase", "and itk", "which are", "are crucial", "crucial for", "for amplifying", "amplifying the", "the t", "t cell", "cell activation", "activation signal", "signal initiated", "initiated by", "by the", "cell receptor", "tcr .", ". grb2", "in particular", "works in", "in tandem", "tandem with", "with vav1", "vav1 to", "to enhance", "enhance the", "the activation", "activation of", "of nfat", "nfat and", "and ap", "ap 1", "1 transcription", "transcription factors", "critical regulators", "regulators of", "of gene", "gene expression", "expression during", "during t", "cell activation.", "activation. cd28", "cd28 costimulation", "costimulation significantly", "significantly extends", "extends the", "the duration", "duration and", "and intensity", "intensity of", "of vav1", "vav1 phosphorylation", "phosphorylation and", "and its", "its localization", "localization at", "at the", "the plasma", "plasma membrane", "membrane compared", "compared to", "to tcr", "tcr activation", "activation alone", "indicating that", "that cd28", "cd28 provides", "provides a", "a sustained", "sustained signal", "signal that", "that enhances", "enhances t", "cell responsiveness", "hehner et", "et al.", "al. 2000", "2000 .
vav1", ".
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additionally", "vav1's involvement", "involvement in", "in cd28", "costimulation is", "is critical", "critical for", "for several", "several other", "other cellular", "cellular processes", "including calcium", "calcium flux", "erk mapk", "mapk activation", "nf \u03bab", "\u03bab signaling", "and the", "the inside", "inside out", "out activation", "of the", "the integrin", "integrin lfa", "lfa 1.", "1. this", "this enhances", "cell adhesion", "and polarization", "ultimately contributing", "contributing to", "to more", "more effective", "effective immune", "immune responses.", "responses. thus", "costimulation ensures", "ensures that", "that vav1", "vav1 mediated", "mediated signals", "signals are", "are robustly", "robustly sustained", "promoting optimal", "optimal t", "activation and", "and function", "2000 .", "cd28 binds to", "binds to several", "to several intracellular", "several intracellular signaling", "intracellular signaling proteins", "proteins including", "including pi3 kinase", "kinase grb2", "grb2 gads", "gads and", "itk which", "which are crucial", "are crucial for", "crucial for amplifying", "for amplifying the", "amplifying the t", "the t cell", "t cell activation", "cell activation signal", "activation signal initiated", "signal initiated by", "initiated by the", "by the t", "t cell receptor", "receptor tcr", "tcr . grb2", "grb2 in", "particular works", "works in tandem", "in tandem with", "tandem with vav1", "with vav1 to", "vav1 to enhance", "to enhance the", "enhance the activation", "the activation of", "activation of nfat", "of nfat and", "nfat and ap", "and ap 1", "ap 1 transcription", "1 transcription factors", "factors critical", "critical regulators of", "regulators of gene", "of gene expression", "gene expression during", "expression during t", "during t cell", "t cell activation.", "cell activation. cd28", "activation. cd28 costimulation", "cd28 costimulation significantly", "costimulation significantly extends", "significantly extends the", "extends the duration", "the duration and", "duration and intensity", "and intensity of", "intensity of vav1", "of vav1 phosphorylation", "vav1 phosphorylation and", "phosphorylation and its", "and its localization", "its localization at", "localization at the", "at the plasma", "the plasma membrane", "plasma membrane compared", "membrane compared to", "compared to tcr", "to tcr activation", "tcr activation alone", "alone indicating", "indicating that cd28", "that cd28 provides", "cd28 provides a", "provides a sustained", "a sustained signal", "sustained signal that", "signal that enhances", "that enhances t", "enhances t cell", "t cell responsiveness", "responsiveness hehner", "hehner et al.", "et al. 2000", "al. 2000 .
vav1", "2000 .
vav1 plays", ".
vav1 plays a", "plays a pivotal", "a pivotal role", "pivotal role in", "role in transducing", "in transducing signals", "transducing signals from", "signals from both", "from both tcr", "both tcr and", "tcr and cd28", "and cd28 to", "cd28 to multiple", "to multiple downstream", "multiple downstream pathways", "pathways with", "with a direct", "a direct impact", "direct impact on", "impact on cytoskeletal", "on cytoskeletal rearrangements.", "cytoskeletal rearrangements. upon", "rearrangements. upon activation", "activation vav1", "vav1 triggers the", "triggers the small", "the small gtpases", "small gtpases rac1", "gtpases rac1 and", "rac1 and cdc42", "cdc42 which", "which lead to", "lead to the", "to the activation", "activation of mitogen", "of mitogen activated", "mitogen activated protein", "activated protein kinases", "kinases mapks", "mapks like", "like jnk and", "jnk and p38.", "and p38. in", "p38. in the", "in the context", "the context of", "context of cd28", "of cd28 signaling", "signaling these", "these pathways are", "pathways are essential", "are essential for", "essential for regulating", "for regulating the", "regulating the expression", "the expression of", "expression of cytokines", "of cytokines and", "cytokines and promoting", "and promoting t", "promoting t cell", "t cell proliferation", "cell proliferation and", "proliferation and survival", "survival laura", "laura in\u00e9s salazar", "in\u00e9s salazar fontana", "salazar fontana et", "fontana et al.", "et al. 2003", "al. 2003 .
additionally", ".
additionally vav1's", "vav1's involvement in", "involvement in cd28", "in cd28 costimulation", "cd28 costimulation is", "costimulation is critical", "is critical for", "critical for several", "for several other", "several other cellular", "other cellular processes", "processes including", "including calcium flux", "flux erk", "erk mapk activation", "activation nf", "nf \u03bab signaling", "signaling and", "and the inside", "the inside out", "inside out activation", "out activation of", "activation of the", "of the integrin", "the integrin lfa", "integrin lfa 1.", "lfa 1. this", "1. this enhances", "this enhances t", "t cell adhesion", "adhesion clustering", "clustering and", "polarization ultimately", "ultimately contributing to", "contributing to more", "to more effective", "more effective immune", "effective immune responses.", "immune responses. thus", "thus cd28", "cd28 costimulation ensures", "costimulation ensures that", "ensures that vav1", "that vav1 mediated", "vav1 mediated signals", "mediated signals are", "signals are robustly", "are robustly sustained", "sustained promoting", "promoting optimal t", "optimal t cell", "cell activation and", "activation and function", "function hehner", "al. 2000 .", "cd28 binds to several", "binds to several intracellular", "to several intracellular signaling", "several intracellular signaling proteins", "signaling proteins including", "proteins including pi3", "pi3 kinase grb2", "gads and itk", "and itk which", "itk which are", "which are crucial for", "are crucial for amplifying", "crucial for amplifying the", "for amplifying the t", "amplifying the t cell", "the t cell activation", "t cell activation signal", "cell activation signal initiated", "activation signal initiated by", "signal initiated by the", "initiated by the t", "by the t cell", "the t cell receptor", "cell receptor tcr", "receptor tcr .", ". grb2 in", "grb2 in particular", "in particular works", "particular works in", "works in tandem with", "in tandem with vav1", "tandem with vav1 to", "with vav1 to enhance", "vav1 to enhance the", "to enhance the activation", "enhance the activation of", "the activation of nfat", "activation of nfat and", "of nfat and ap", "nfat and ap 1", "and ap 1 transcription", "ap 1 transcription factors", "transcription factors critical", "factors critical regulators", "critical regulators of gene", "regulators of gene expression", "of gene expression during", "gene expression during t", "expression during t cell", "during t cell activation.", "t cell activation. cd28", "cell activation. cd28 costimulation", "activation. cd28 costimulation significantly", "cd28 costimulation significantly extends", "costimulation significantly extends the", "significantly extends the duration", "extends the duration and", "the duration and intensity", "duration and intensity of", "and intensity of vav1", "intensity of vav1 phosphorylation", "of vav1 phosphorylation and", "vav1 phosphorylation and its", "phosphorylation and its localization", "and its localization at", "its localization at the", "localization at the plasma", "at the plasma membrane", "the plasma membrane compared", "plasma membrane compared to", "membrane compared to tcr", "compared to tcr activation", "to tcr activation alone", "activation alone indicating", "alone indicating that", "indicating that cd28 provides", "that cd28 provides a", "cd28 provides a sustained", "provides a sustained signal", "a sustained signal that", "sustained signal that enhances", "signal that enhances t", "that enhances t cell", "enhances t cell responsiveness", "cell responsiveness hehner", "responsiveness hehner et", "hehner et al. 2000", "et al. 2000 .
vav1", "al. 2000 .
vav1 plays", "2000 .
vav1 plays a", ".
vav1 plays a pivotal", "plays a pivotal role", "a pivotal role in", "pivotal role in transducing", "role in transducing signals", "in transducing signals from", "transducing signals from both", "signals from both tcr", "from both tcr and", "both tcr and cd28", "tcr and cd28 to", "and cd28 to multiple", "cd28 to multiple downstream", "to multiple downstream pathways", "downstream pathways with", "pathways with a", "with a direct impact", "a direct impact on", "direct impact on cytoskeletal", "impact on cytoskeletal rearrangements.", "on cytoskeletal rearrangements. upon", "cytoskeletal rearrangements. upon activation", "upon activation vav1", "activation vav1 triggers", "vav1 triggers the small", "triggers the small gtpases", "the small gtpases rac1", "small gtpases rac1 and", "gtpases rac1 and cdc42", "and cdc42 which", "cdc42 which lead", "which lead to the", "lead to the activation", "to the activation of", "the activation of mitogen", "activation of mitogen activated", "of mitogen activated protein", "mitogen activated protein kinases", "protein kinases mapks", "mapks like jnk", "like jnk and p38.", "jnk and p38. in", "and p38. in the", "p38. in the context", "in the context of", "the context of cd28", "context of cd28 signaling", "cd28 signaling these", "signaling these pathways", "these pathways are essential", "pathways are essential for", "are essential for regulating", "essential for regulating the", "for regulating the expression", "regulating the expression of", "the expression of cytokines", "expression of cytokines and", "of cytokines and promoting", "cytokines and promoting t", "and promoting t cell", "promoting t cell proliferation", "t cell proliferation and", "cell proliferation and survival", "and survival laura", "survival laura in\u00e9s", "laura in\u00e9s salazar fontana", "in\u00e9s salazar fontana et", "salazar fontana et al.", "fontana et al. 2003", "et al. 2003 .
additionally", "2003 .
additionally vav1's", ".
additionally vav1's involvement", "vav1's involvement in cd28", "involvement in cd28 costimulation", "in cd28 costimulation is", "cd28 costimulation is critical", "costimulation is critical for", "is critical for several", "critical for several other", "for several other cellular", "several other cellular processes", "cellular processes including", "processes including calcium", "calcium flux erk", "flux erk mapk", "mapk activation nf", "activation nf \u03bab", "\u03bab signaling and", "signaling and the", "and the inside out", "the inside out activation", "inside out activation of", "out activation of the", "activation of the integrin", "of the integrin lfa", "the integrin lfa 1.", "integrin lfa 1. this", "lfa 1. this enhances", "1. this enhances t", "this enhances t cell", "enhances t cell adhesion", "cell adhesion clustering", "clustering and polarization", "and polarization ultimately", "polarization ultimately contributing", "ultimately contributing to more", "contributing to more effective", "to more effective immune", "more effective immune responses.", "effective immune responses. thus", "responses. thus cd28", "thus cd28 costimulation", "cd28 costimulation ensures that", "costimulation ensures that vav1", "ensures that vav1 mediated", "that vav1 mediated signals", "vav1 mediated signals are", "mediated signals are robustly", "signals are robustly sustained", "robustly sustained promoting", "sustained promoting optimal", "promoting optimal t cell", "optimal t cell activation", "t cell activation and", "cell activation and function", "and function hehner", "function hehner et", "et al. 2000 .", "cd28 binds to several intracellular", "binds to several intracellular signaling", "to several intracellular signaling proteins", "intracellular signaling proteins including", "signaling proteins including pi3", "proteins including pi3 kinase", "including pi3 kinase grb2", "kinase grb2 gads", "grb2 gads and", "and itk which are", "itk which are crucial", "which are crucial for amplifying", "are crucial for amplifying the", "crucial for amplifying the t", "for amplifying the t cell", "amplifying the t cell activation", "the t cell activation signal", "t cell activation signal initiated", "cell activation signal initiated by", "activation signal initiated by the", "signal initiated by the t", "initiated by the t cell", "by the t cell receptor", "t cell receptor tcr", "cell receptor tcr .", "receptor tcr . grb2", "tcr . grb2 in", ". grb2 in particular", "in particular works in", "particular works in tandem", "works in tandem with vav1", "in tandem with vav1 to", "tandem with vav1 to enhance", "with vav1 to enhance the", "vav1 to enhance the activation", "to enhance the activation of", "enhance the activation of nfat", "the activation of nfat and", "activation of nfat and ap", "of nfat and ap 1", "nfat and ap 1 transcription", "and ap 1 transcription factors", "1 transcription factors critical", "transcription factors critical regulators", "factors critical regulators of", "critical regulators of gene expression", "regulators of gene expression during", "of gene expression during t", "gene expression during t cell", "expression during t cell activation.", "during t cell activation. cd28", "t cell activation. cd28 costimulation", "cell activation. cd28 costimulation significantly", "activation. cd28 costimulation significantly extends", "cd28 costimulation significantly extends the", "costimulation significantly extends the duration", "significantly extends the duration and", "extends the duration and intensity", "the duration and intensity of", "duration and intensity of vav1", "and intensity of vav1 phosphorylation", "intensity of vav1 phosphorylation and", "of vav1 phosphorylation and its", "vav1 phosphorylation and its localization", "phosphorylation and its localization at", "and its localization at the", "its localization at the plasma", "localization at the plasma membrane", "at the plasma membrane compared", "the plasma membrane compared to", "plasma membrane compared to tcr", "membrane compared to tcr activation", "compared to tcr activation alone", "tcr activation alone indicating", "activation alone indicating that", "alone indicating that cd28", "indicating that cd28 provides a", "that cd28 provides a sustained", "cd28 provides a sustained signal", "provides a sustained signal that", "a sustained signal that enhances", "sustained signal that enhances t", "signal that enhances t cell", "that enhances t cell responsiveness", "t cell responsiveness hehner", "cell responsiveness hehner et", "responsiveness hehner et al.", "hehner et al. 2000 .
vav1", "et al. 2000 .
vav1 plays", "al. 2000 .
vav1 plays a", "2000 .
vav1 plays a pivotal", ".
vav1 plays a pivotal role", "plays a pivotal role in", "a pivotal role in transducing", "pivotal role in transducing signals", "role in transducing signals from", "in transducing signals from both", "transducing signals from both tcr", "signals from both tcr and", "from both tcr and cd28", "both tcr and cd28 to", "tcr and cd28 to multiple", "and cd28 to multiple downstream", "cd28 to multiple downstream pathways", "multiple downstream pathways with", "downstream pathways with a", "pathways with a direct", "with a direct impact on", "a direct impact on cytoskeletal", "direct impact on cytoskeletal rearrangements.", "impact on cytoskeletal rearrangements. upon", "on cytoskeletal rearrangements. upon activation", "rearrangements. upon activation vav1", "upon activation vav1 triggers", "activation vav1 triggers the", "vav1 triggers the small gtpases", "triggers the small gtpases rac1", "the small gtpases rac1 and", "small gtpases rac1 and cdc42", "rac1 and cdc42 which", "and cdc42 which lead", "cdc42 which lead to", "which lead to the activation", "lead to the activation of", "to the activation of mitogen", "the activation of mitogen activated", "activation of mitogen activated protein", "of mitogen activated protein kinases", "activated protein kinases mapks", "kinases mapks like", "mapks like jnk and", "like jnk and p38. in", "jnk and p38. in the", "and p38. in the context", "p38. in the context of", "in the context of cd28", "the context of cd28 signaling", "of cd28 signaling these", "cd28 signaling these pathways", "signaling these pathways are", "these pathways are essential for", "pathways are essential for regulating", "are essential for regulating the", "essential for regulating the expression", "for regulating the expression of", "regulating the expression of cytokines", "the expression of cytokines and", "expression of cytokines and promoting", "of cytokines and promoting t", "cytokines and promoting t cell", "and promoting t cell proliferation", "promoting t cell proliferation and", "t cell proliferation and survival", "proliferation and survival laura", "and survival laura in\u00e9s", "survival laura in\u00e9s salazar", "laura in\u00e9s salazar fontana et", "in\u00e9s salazar fontana et al.", "salazar fontana et al. 2003", "fontana et al. 2003 .
additionally", "al. 2003 .
additionally vav1's", "2003 .
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by changing", "transmission by changing the", "by changing the type and", "changing the type and the", "the type and the number", "type and the number of", "and the number of ampa", "the number of ampa receptors.", "number of ampa receptors. these", "of ampa receptors. these changes", "ampa receptors. these changes are", "receptors. these changes are brought", "these changes are brought about", "changes are brought about by", "are brought about by trafficking", "brought about by trafficking mechanisms", "about by trafficking mechanisms that", "by trafficking mechanisms that are", "trafficking mechanisms that are mainly", "mechanisms that are mainly controlled", "that are mainly controlled by", "are mainly controlled by activity", "mainly controlled by activity dependent", "controlled by activity dependent phosphorylation/desphosphorylation", "by activity dependent phosphorylation/desphosphorylation of", "activity dependent phosphorylation/desphosphorylation of the", "dependent phosphorylation/desphosphorylation of the glur1/glur2", "phosphorylation/desphosphorylation of the glur1/glur2 subunits." ] }, { "record_id": "GLY_000594_1_954", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "399997", "r hsa", "hsa 399997", "r hsa 399997" ] }, { "record_id": "GLY_000594_1_954", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "acetylcholine regulates", "regulates insulin", "insulin secretion", "acetylcholine regulates insulin", "regulates insulin secretion", "acetylcholine regulates insulin secretion", "acetylcholine released", "released by", "by parasympathetic", "parasympathetic nerve", "nerve endings", "endings in", "in the", "the pancreas", "pancreas causes", "causes a", "a potentiation", "potentiation of", "of insulin", "insulin release", "release when", "when glucose", "glucose is", "is present", "present at", "at concentrations", "concentrations greater", "greater than", 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dag", "trisphosphate.
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dag", "5 trisphosphate.
dag remains", "trisphosphate.
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inositol", "to acetylcholine.
inositol trisphophate", "acetylcholine.
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after acetylcholine binds the", "binds the muscarinic acetycholine", "the muscarinic acetycholine receptor", "muscarinic acetycholine receptor m3", "receptor m3 the", "m3 the receptor", "the receptor activates the", "receptor activates the g", "activates the g protein", "the g protein gq", "g protein gq by", "protein gq by causing", "gq by causing the", "by causing the alpha", "causing the alpha subunit", "the alpha subunit of", "alpha subunit of gq", "subunit of gq to", "of gq to exchange", "gq to exchange gdp", "to exchange gdp for", "exchange gdp for gtp.", "gdp for gtp. activation", "for gtp. activation of", "gtp. activation of gq", "activation of gq in", "of gq in turn", "gq in turn activates", "in turn activates phospholipase", "turn activates phospholipase c", "activates phospholipase c beta", "phospholipase c beta 1.", "c beta 1. phospholipase", "beta 1. phospholipase c", "1. phospholipase c beta", "c beta 1 hydrolyzes", "beta 1 hydrolyzes the", "1 hydrolyzes the phosphodiester", "hydrolyzes the phosphodiester bond", "the phosphodiester bond at", "phosphodiester bond at the", "bond at the third", "at the third position", "the third position of", "third position of phosphoinositol", "position of phosphoinositol 4", "of phosphoinositol 4 5", "phosphoinositol 4 5 bisphosphate", "5 bisphosphate producing", "bisphosphate producing diacylglycerols", "producing diacylglycerols dag", "dag and inositol", "and inositol 1 4", "inositol 1 4 5", "1 4 5 trisphosphate.
dag", "4 5 trisphosphate.
dag remains", "5 trisphosphate.
dag remains in", "trisphosphate.
dag remains in the", "remains in the cell", "in the cell membrane", "the cell membrane and", "cell membrane and causes", "membrane and causes protein", "and causes protein kinase", "causes protein kinase c", "protein kinase c alpha", "c alpha pkc", "alpha pkc alpha", "pkc alpha to", "alpha to translocate", "to translocate from the", "translocate from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the membrane.", "to the membrane. this", "the membrane. this results", "membrane. this results in", "this results in the", "results in the activation", "in the activation of", "the activation of pkc", "activation of pkc alpha", "of pkc alpha which", "pkc alpha which then", "alpha which then phosphorylates", "which then phosphorylates target", "then phosphorylates target proteins", "phosphorylates target proteins on", "target proteins on serine", "proteins on serine and", "on serine and threonine", "serine and threonine residues.", "and threonine residues. one", "threonine residues. one known", "residues. one known target", "one known target of", "known target of pkc", "target of pkc alpha", "of pkc alpha is", "pkc alpha is myristoylated", "alpha is myristoylated alanine", "is myristoylated alanine rich", "myristoylated alanine rich c", "alanine rich c kinase", "rich c kinase substrate", "kinase substrate marcks", "marcks which", "which is believed to", "is believed to affect", "believed to affect vesicle", "to affect vesicle transport", "affect vesicle transport and", "vesicle transport and may", "transport and may be", "and may be responsible", "may be responsible for", "be responsible for the", "responsible for the increased", "for the increased traffic", "the increased traffic of", "increased traffic of insulin", "traffic of insulin granules", "of insulin granules seen", "insulin granules seen in", "granules seen in response", "seen in response to", "in response to acetylcholine.
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inositol trisphophate", "to acetylcholine.
inositol trisphophate binds", "acetylcholine.
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after", "g q .
after acetylcholine binds", "q .
after acetylcholine binds the", ".
after acetylcholine binds the muscarinic", "acetylcholine binds the muscarinic acetycholine", "binds the muscarinic acetycholine receptor", "the muscarinic acetycholine receptor m3", "acetycholine receptor m3 the", "receptor m3 the receptor", "m3 the receptor activates", "the receptor activates the g", "receptor activates the g protein", "activates the g protein gq", "the g protein gq by", "g protein gq by causing", "protein gq by causing the", "gq by causing the alpha", "by causing the alpha subunit", "causing the alpha subunit of", "the alpha subunit of gq", "alpha subunit of gq to", "subunit of gq to exchange", "of gq to exchange gdp", "gq to exchange gdp for", "to exchange gdp for gtp.", "exchange gdp for gtp. activation", "gdp for gtp. activation of", "for gtp. activation of gq", "gtp. activation of gq in", "activation of gq in turn", "of gq in turn activates", "gq in turn activates phospholipase", "in turn activates phospholipase c", "turn activates phospholipase c beta", "activates phospholipase c beta 1.", "phospholipase c beta 1. phospholipase", "c beta 1. phospholipase c", "beta 1. phospholipase c beta", "1. phospholipase c beta 1", "phospholipase c beta 1 hydrolyzes", "c beta 1 hydrolyzes the", "beta 1 hydrolyzes the phosphodiester", "1 hydrolyzes the phosphodiester bond", "hydrolyzes the phosphodiester bond at", "the phosphodiester bond at the", "phosphodiester bond at the third", "bond at the third position", "at the third position of", "the third position of phosphoinositol", "third position of phosphoinositol 4", "position of phosphoinositol 4 5", "of phosphoinositol 4 5 bisphosphate", "4 5 bisphosphate producing", "5 bisphosphate producing diacylglycerols", "diacylglycerols dag and", "dag and inositol 1", "and inositol 1 4 5", "inositol 1 4 5 trisphosphate.
dag", "1 4 5 trisphosphate.
dag remains", "4 5 trisphosphate.
dag remains in", "5 trisphosphate.
dag remains in the", "trisphosphate.
dag remains in the cell", "remains in the cell membrane", "in the cell membrane and", "the cell membrane and causes", "cell membrane and causes protein", "membrane and causes protein kinase", "and causes protein kinase c", "causes protein kinase c alpha", "kinase c alpha pkc", "c alpha pkc alpha", "pkc alpha to translocate", "alpha to translocate from", "to translocate from the cytosol", "translocate from the cytosol to", "from the cytosol to the", "the cytosol to the membrane.", "cytosol to the membrane. this", "to the membrane. this results", "the membrane. this results in", "membrane. this results in the", "this results in the activation", "results in the activation of", "in the activation of pkc", "the activation of pkc alpha", "activation of pkc alpha which", "of pkc alpha which then", "pkc alpha which then phosphorylates", "alpha which then phosphorylates target", "which then phosphorylates target proteins", "then phosphorylates target proteins on", "phosphorylates target proteins on serine", "target proteins on serine and", "proteins on serine and threonine", "on serine and threonine residues.", "serine and threonine residues. one", "and threonine residues. one known", "threonine residues. one known target", "residues. one known target of", "one known target of pkc", "known target of pkc alpha", "target of pkc alpha is", "of pkc alpha is myristoylated", "pkc alpha is myristoylated alanine", "alpha is myristoylated alanine rich", "is myristoylated alanine rich c", "myristoylated alanine rich c kinase", "alanine rich c kinase substrate", "c kinase substrate marcks", "marcks which is", "which is believed to affect", "is believed to affect vesicle", "believed to affect vesicle transport", "to affect vesicle transport and", "affect vesicle transport and may", "vesicle transport and may be", "transport and may be responsible", "and may be responsible for", "may be responsible for the", "be responsible for the increased", "responsible for the increased traffic", "for the increased traffic of", "the increased traffic of insulin", "increased traffic of insulin granules", "traffic of insulin granules seen", "of insulin granules seen in", "insulin granules seen in response", "granules seen in response to", "seen in response to acetylcholine.
inositol", "in response to acetylcholine.
inositol trisphophate", "response to acetylcholine.
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"hsa 4090294", "r hsa 4090294" ] }, { "record_id": "GLY_000594_1_955", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sumoylation of", "of intracellular", "intracellular receptors", "sumoylation of intracellular", "of intracellular receptors", "sumoylation of intracellular receptors", "at least", "least 17", "17 nuclear", "nuclear receptors", "receptors have", "have been", "been discovered", "discovered to", "to be", "be sumoylated", "reviewed in", "in treuter", "treuter and", "and venteclef", "venteclef 2011", "wadosky et", "et al.", "al. 2012", "knutson and", "and lange", "lange 2013", "2013 .", ". in", "in all", "all but", "but a", "a few", "few cases", "notably ar", "ar and", "and rora", "sumoylation causes", "causes transcriptional", "transcriptional repression.", "repression. repression", "repression by", "by sumoylation", "sumoylation is", "is believed", "believed to", "to occur", "occur through", "through several", "several mechanisms:", 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synapse. phosphorylation", "at the synapse. phosphorylation of", "the synapse. phosphorylation of glur2", "synapse. phosphorylation of glur2 at", "phosphorylation of glur2 at s880", "of glur2 at s880 disrupts", "glur2 at s880 disrupts grip", "at s880 disrupts grip interaction", "s880 disrupts grip interaction but", "disrupts grip interaction but allows", "grip interaction but allows binding", "interaction but allows binding of", "but allows binding of pick.", "allows binding of pick. pick", "binding of pick. pick is", "of pick. pick is activated", "pick. pick is activated by", "pick is activated by ca", "is activated by ca sensitive", "activated by ca sensitive protein", "by ca sensitive protein kinase", "ca sensitive protein kinase c", "protein kinase c pkc", "kinase c pkc .", "c pkc . under", "pkc . under basal conditions", "under basal conditions in", "basal conditions in hippocampal", "conditions in hippocampal synapse", "in hippocampal synapse glur2", "hippocampal synapse glur2 containing", "synapse glur2 containing ampa", "containing ampa receptors glur2/glur3", "receptors glur2/glur3 constitutively", "glur2/glur3 constitutively recycle between", "constitutively recycle between the synapse", "recycle between the synapse and", "between the synapse and the", "the synapse and the endosome", "synapse and the endosome by", "and the endosome by endocytosis", "the endosome by endocytosis and", "endosome by endocytosis and exocytosis.", "by endocytosis and exocytosis. grip", "endocytosis and exocytosis. grip anchors", "and exocytosis. grip anchors the", "exocytosis. grip anchors the receptors", "grip anchors the receptors at", "anchors the receptors at the", "the receptors at the synapse", "receptors at the synapse while", "at the synapse while pick", "the synapse while pick interaction", "synapse while pick interaction internalizes", "while pick interaction internalizes the", "pick interaction internalizes the receptors", "interaction internalizes the receptors and", "internalizes the receptors and nsf", "the receptors and nsf helps", "receptors and nsf helps maintain", "and nsf helps maintain the", "nsf helps maintain the synaptic", "helps maintain the synaptic receptors.", "maintain the synaptic receptors. cerebellar", "the synaptic receptors. cerebellar stellate", "synaptic receptors. cerebellar stellate cells", "receptors. cerebellar stellate cells mainly", "cerebellar stellate cells mainly contain", "stellate cells mainly contain glur3", "cells mainly contain glur3 homomers", "mainly contain glur3 homomers as", "contain glur3 homomers as ca", "glur3 homomers as ca permeable", "homomers as ca permeable receptors.", "as ca permeable receptors. the", "ca permeable receptors. the interaction", "permeable receptors. the interaction of", "receptors. the interaction of glur3", "the interaction of glur3 and", "interaction of glur3 and grip", "of glur3 and grip is", "glur3 and grip is disrupted", "and grip is disrupted by", "grip is disrupted by pick", "is disrupted by pick interaction", "disrupted by pick interaction by", "by pick interaction by phosphorylation", "pick interaction by phosphorylation of", "interaction by phosphorylation of equivalent", "by phosphorylation of equivalent of", "phosphorylation of equivalent of s880", "of equivalent of s880 residue", "equivalent of s880 residue in", "of s880 residue in glur3.", "residue in glur3. under", "in glur3. under conditions", "glur3. under conditions of", "under conditions of repetitive presynaptic", "conditions of repetitive presynaptic activity", "repetitive presynaptic activity there", "presynaptic activity there is", "activity there is pick", "there is pick dependent removal", "is pick dependent removal of", "pick dependent removal of glur2", "dependent removal of glur2 lacking", "removal of glur2 lacking ampa", "of glur2 lacking ampa receptors", "glur2 lacking ampa receptors and", "lacking ampa receptors and selective", "ampa receptors and selective incorporation", "receptors and selective incorporation of", "and selective incorporation of glur2", "selective incorporation of glur2 containing", "incorporation of glur2 containing ampa", "glur2 containing ampa receptors at", "containing ampa receptors at the", "receptors at the synapse. the", "at the synapse. the glur2", "the synapse. the glur2 containing", "synapse. the glur2 containing ampa", "the glur2 containing ampa receptors", "glur2 containing ampa receptors are", "containing ampa receptors are first", "ampa receptors are first delivered", "receptors are first delivered to", "are first delivered to the", "first delivered to the surface", "delivered to the surface by", "to the surface by pick", "the surface by pick and", "surface by pick and mobilized", "by pick and mobilized to", "pick and mobilized to the", "and mobilized to the synapse", "mobilized to the synapse by", "to the synapse by nsf", "the synapse by nsf dependent", "synapse by nsf dependent mechanism", "nsf dependent mechanism liu", "dependent mechanism liu sj", "mechanism liu sj and", "liu sj and cull candy", "sj and cull candy sg", "and cull candy sg nat", "cull candy sg nat neurosci.", "candy sg nat neurosci. 2005", "sg nat neurosci. 2005 jun", "nat neurosci. 2005 jun 8", "neurosci. 2005 jun 8 6", "2005 jun 8 6 :768", "jun 8 6 :768 75" ] }, { "record_id": "GLY_000594_1_958", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "418346", "r hsa", "hsa 418346", "r hsa 418346" ] }, { "record_id": "GLY_000594_1_958", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "platelet homeostasis", "under normal", "normal conditions", "conditions the", "the vascular", "vascular endothelium", "endothelium supports", "supports vasodilation", "inhibits platelet", "platelet adhesion", "adhesion and", "and activation", "suppresses coagulation", "enhances fibrin", "fibrin cleavage", "cleavage and", "and is", "is anti", "anti inflammatory", 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the", "fluids and tissues.
the receptor", "and tissues.
the receptor family", "tissues.
the receptor family for", "receptor family for these", "family for these peptides", "for these peptides consists", "these peptides consists of", "peptides consists of two", "consists of two class", "of two class b", "two class b gpcrs", "b gpcrs the", "gpcrs the calcitonin", "calcitonin receptor ct", "ct and calcitonin", "and calcitonin receptor like", "calcitonin receptor like receptor", "like receptor cl", "cl poyner", "poyner dr er al", "er al 2002", "al 2002 .", "2002 . whilst the", ". whilst the receptor", "whilst the receptor for", "the receptor for calcitonin", "receptor for calcitonin is", "for calcitonin is a", "calcitonin is a conventional", "is a conventional class", "a conventional class b", "conventional class b gpcr", "b gpcr the", "gpcr the receptors", "the receptors for cgrp", "for cgrp am", "cgrp am and", "am and amylin require", "and amylin require additional", "amylin require additional proteins", "additional proteins called", "proteins called the", "called the receptor activity", "the receptor activity modifying", "receptor activity modifying proteins", "modifying proteins ramps", "proteins ramps .", "ramps . there are", ". there are three", "there are three ramps", "are three ramps in", "three ramps in mammals", "in mammals they", "mammals they interact", "they interact with the", "interact with the ct", "with the ct receptor", "the ct receptor to", "ct receptor to convert", "receptor to convert it", "to convert it to", "convert it to receptors", "it to receptors for", "to receptors for amylin.", "receptors for amylin. for", "for amylin. for cgrp", "amylin. for cgrp and", "for cgrp and am", "and am the", "am the related", "the related cl interacts", "related cl interacts with", "cl interacts with ramp1", "interacts with ramp1 to", "with ramp1 to give", "ramp1 to give a", "to give a cgrp", "give a cgrp receptor", "a cgrp receptor and", "cgrp receptor and ramp2", "receptor and ramp2 or", "and ramp2 or 3", "ramp2 or 3 to", "or 3 to give", "3 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product of the", "a product of the islet", "product of the islet beta", "of the islet beta cell", "islet beta cell cooper", "beta cell cooper gj", "cell cooper gj et", "gj et al 1987", "1987 along with", "along with insulin and probably", "with insulin and probably has", "insulin and probably has a", "and probably has a hormonal", "probably has a hormonal role", "has a hormonal role in", "a hormonal role in the", "hormonal role in the regulation", "role in the regulation of", "in the regulation of nutrient", "the regulation of nutrient intake", "of nutrient intake young", "nutrient intake young a", "intake young a and", "young a and denaro m", "and denaro m 1998", "denaro m 1998 .", "m 1998 . adrenomedullin", "1998 . adrenomedullin am", "adrenomedullin am is", "am is a ubiquitously", "is a ubiquitously expressed peptide", "a ubiquitously expressed peptide initially", "ubiquitously expressed peptide initially isolated", "expressed peptide initially isolated from", "peptide initially 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functions and the chemical", "functions and the chemical composition", "and the chemical composition of", "the chemical composition of fluids", "chemical composition of fluids and", "composition of fluids and tissues.
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the receptor family for these", "receptor family for these peptides", "family for these peptides consists", "for these peptides consists of", "these peptides consists of two", "peptides consists of two class", "consists of two class b", "of two class b gpcrs", "class b gpcrs the", "b gpcrs the calcitonin", "gpcrs the calcitonin receptor", "the calcitonin receptor ct", "receptor ct and", "ct and calcitonin receptor", "and calcitonin receptor like receptor", "receptor like receptor cl", "cl poyner dr", "dr er al 2002", "er al 2002 .", "al 2002 . whilst", "2002 . whilst the receptor", ". whilst the receptor for", "whilst the receptor for calcitonin", "the receptor for calcitonin is", "receptor for calcitonin is a", "for calcitonin is a conventional", "calcitonin is a conventional class", "is a conventional class b", "a conventional class b gpcr", "class b gpcr the", "b gpcr the receptors", "gpcr the receptors for", "receptors for cgrp am", "for cgrp am and", "cgrp am and amylin", "am and amylin require additional", "and amylin require additional proteins", "require additional proteins called", "additional proteins called the", "proteins called the receptor", "called the receptor activity modifying", "the receptor activity modifying proteins", "activity modifying proteins ramps", "modifying proteins ramps .", "proteins ramps . there", "ramps . there are three", ". there are three ramps", "there are three ramps in", "are three ramps in mammals", "ramps in mammals they", "in mammals they interact", "mammals they interact with", "they interact with the ct", "interact with the ct receptor", "with the ct receptor to", "the ct receptor to convert", "ct receptor to convert it", "receptor to convert it to", "to convert it to receptors", "convert it to receptors for", "it to receptors for amylin.", "to receptors for amylin. for", "receptors for amylin. for cgrp", "for amylin. for cgrp and", "amylin. for cgrp and am", "cgrp and am the", "and am the related", "am the related cl", "the related cl interacts with", "related cl interacts with ramp1", "cl interacts with ramp1 to", "interacts with ramp1 to give", "with ramp1 to give a", "ramp1 to give a cgrp", "to give a cgrp receptor", "give a cgrp receptor and", "a cgrp receptor and ramp2", "cgrp receptor and ramp2 or", "receptor and ramp2 or 3", "and ramp2 or 3 to", "ramp2 or 3 to give", "or 3 to give am", "3 to give am receptors.", "to give am receptors. cl", "give am receptors. cl by", "am receptors. cl by itself", "receptors. cl by itself will", "cl by itself will bind", "by itself will bind no", "itself will bind no known", "will bind no known endogenous", "bind no known endogenous ligand." ] }, { "record_id": "GLY_000594_1_965", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "422085", "r hsa", "hsa 422085", "r hsa 422085" ] }, { "record_id": "GLY_000594_1_965", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "and deacylation", "deacylation of", "of ghrelin", "synthesis secretion", "secretion and", "and deacylation of", "deacylation of ghrelin", "secretion and deacylation", "and deacylation of ghrelin", "synthesis secretion and", "secretion and deacylation of", "ghrelin is", "is a", "a peptide", "peptide hormone", "hormone of", "of 28", "28 amino", "amino acid", "acid residues", "residues which", "which is", "is acylated", "acylated at", "at the", "the serine", "serine 3", "3 of", "of the", "the mature", "mature peptide.", "peptide. ghrelin", "is synthesized", "synthesized in", "in several", "several tissues:", "tissues: x/a", "x/a like", "like cells", "cells of", "the gastric", "gastric mucosa", "the major", "major source", "source of", "adrenal gland", "fallopian tube", "gall bladder", "fat tissue", "human lymphocytes", "skeletal muscle", "vein and", "and skin.", "skin. ghrelin", "ghrelin binds", "binds the", "the ghs", "ghs r1a", "r1a receptor", "receptor present", "present in", "in hypothalamus", "hypothalamus pituitary", "and other", "other tissues.", "tissues. binding", "binding causes", "causes appetite", "appetite stimulation", "stimulation and", "and release", "release of", "of growth", "growth hormone.", "hormone. levels", "levels of", "of circulating", "circulating ghrelin", "ghrelin rise", "rise during", "during fasting", "peak before", "before a", "a meal", "and fall", "fall according", "according to", "to the", "the calories", "calories ingested.
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preproghrelin is", "the calories ingested.
preproghrelin is cleaved", "calories ingested.
preproghrelin is cleaved to", "ingested.
preproghrelin is cleaved to yield", "is cleaved to yield proghrelin", "cleaved to yield proghrelin which", "to yield proghrelin which is", "yield proghrelin which is then", "proghrelin which is then acylated", "which is then acylated by", "is then acylated by ghrelin", "then acylated by ghrelin o", "acylated by ghrelin o acyltransferase", "by ghrelin o acyltransferase to", "ghrelin o acyltransferase to yield", "o acyltransferase to yield octanoyl", "acyltransferase to yield octanoyl ghrelin", "to yield octanoyl ghrelin and", "yield octanoyl ghrelin and decanoyl", "octanoyl ghrelin and decanoyl ghrelin.", "ghrelin and decanoyl ghrelin. only", "and decanoyl ghrelin. only octanoyl", "decanoyl ghrelin. only octanoyl ghrelin", "ghrelin. only octanoyl ghrelin is", "only octanoyl ghrelin is able", "octanoyl ghrelin is able to", "ghrelin is able to bind", "is able to bind and", "able to bind and activate", "to bind and activate the", "bind and activate the ghs", "and activate the ghs r1a", "activate the ghs r1a receptor.", "the ghs r1a receptor. unacylated", "ghs r1a receptor. unacylated ghrelin", "receptor. unacylated ghrelin des", "unacylated ghrelin des acyl", "ghrelin des acyl ghrelin", "des acyl ghrelin is", "acyl ghrelin is also", "ghrelin is also present", "is also present in plasma", "also present in plasma but", "present in plasma but its", "in plasma but its function", "plasma but its function is", "but its function is controversial.
acyl", "its function is controversial.
acyl proghrelin", "function is controversial.
acyl proghrelin is", "is controversial.
acyl proghrelin is cleaved", "controversial.
acyl proghrelin is cleaved by", "proghrelin is cleaved by prohormone", "is cleaved by prohormone convertase", "cleaved by prohormone convertase 1/3", "by prohormone convertase 1/3 to", "prohormone convertase 1/3 to yield", "convertase 1/3 to yield the", "1/3 to yield the mature", "to yield the mature acyl", "yield the mature acyl ghrelin", "the mature acyl ghrelin and", "mature acyl ghrelin and c", "acyl ghrelin and c ghrelin.", "ghrelin and c ghrelin. secretion", "and c ghrelin. secretion of", "c ghrelin. secretion of ghrelin", "ghrelin. secretion of ghrelin is", "secretion of ghrelin is inhibited", "of ghrelin is inhibited by", "ghrelin is inhibited by insulin", "inhibited by insulin growth", "by insulin growth hormone", "leptin glucose glucagon", "glucose glucagon and", "glucagon and fatty acids.", "and fatty acids. secretion is", "fatty acids. secretion is stimulated", "acids. secretion is stimulated by", "secretion is stimulated by insulin", "is stimulated by insulin like", "stimulated by insulin like growth", "by insulin like growth factor", "insulin like growth factor 1", "like growth factor 1 and", "growth factor 1 and muscarinic", "factor 1 and muscarinic agonists.
in", "1 and muscarinic agonists.
in the", "and muscarinic agonists.
in the bloodstream", "muscarinic agonists.
in the bloodstream acyl", "agonists.
in the bloodstream acyl ghrelin", "the bloodstream acyl ghrelin is", "bloodstream acyl ghrelin is deacylated", "acyl ghrelin is deacylated by", "ghrelin is deacylated by butyrylcholinesterase", "is deacylated by butyrylcholinesterase and", "deacylated by butyrylcholinesterase and platelet", "by butyrylcholinesterase and platelet activating", "butyrylcholinesterase and platelet activating factor", "and platelet activating factor acetylhydrolase.", "platelet activating factor acetylhydrolase. other", "activating factor acetylhydrolase. other enzymes", "factor acetylhydrolase. other enzymes may", "acetylhydrolase. other enzymes may also", "other enzymes may also deacylate", "enzymes may also deacylate acyl", "may also deacylate acyl ghrelin." ] }, { "record_id": "GLY_000594_1_966", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "425561", "r hsa", "hsa 425561", "r hsa 425561" ] }, { "record_id": "GLY_000594_1_966", "filename": 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plasma membranes and intracellular", "plasma membranes and intracellular compartments", "and intracellular compartments lytton", "intracellular compartments lytton j", "lytton j 2007 .", "j 2007 . they", "2007 . they are the", ". they are the na+/ca2+", "they are the na+/ca2+ exchanger", "are the na+/ca2+ exchanger family", "the na+/ca2+ exchanger family designated", "na+/ca2+ exchanger family designated ncx", "family designated ncx slc8", "slc8 three members", "ncx1 3 quednau", "3 quednau bd", "bd et al 2004", "2004 the na+/ca2+", "the na+/ca2+ k+ exchanger family", "na+/ca2+ k+ exchanger family designated", "k+ exchanger family designated nckx", "family designated nckx slc24", "slc24 five members", "nckx1 5 schnetkamp", "5 schnetkamp pp", "pp 2004 and", "2004 and a ca2+/cation", "a ca2+/cation exchanger nckx6", "exchanger nckx6 nclx", "nckx6 nclx whose", "nclx whose physiological function", "whose physiological function remains unclear." ] }, { "record_id": "GLY_000594_1_967", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "426486", "r hsa", "hsa 426486", "r hsa 426486" ] }, { "record_id": "GLY_000594_1_967", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "small interfering", "interfering rna", "small interfering rna", "rna sirna", "sirna biogenesis", "interfering rna sirna", "small interfering rna sirna", "rna sirna biogenesis", "interfering rnas", "are 21", "21 25", "25 nucleotide", "nucleotide single", "single stranded", "stranded rnas", "rnas produced", "produced by", "by cleavage", "cleavage of", "of longer", "longer double", "double stranded", "rnas by", "by the", "the enzyme", "enzyme dicer1", "dicer1 within", "within the", "the risc", "risc loading", "loading complex", "complex containing", "containing dicer1", "an argonaute", "argonaute protein", "and either", "either tarbp2", "tarbp2 or", "or prkra", "pact .", ". typically", "typically the", "the long", 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while", "axons while robo3.2", "while robo3.2 generated", "robo3.2 generated by", "generated by alternative splicing", "alternative splicing is", "splicing is expressed", "is expressed after midline", "expressed after midline crossing", "after midline crossing and", "midline crossing and thought", "crossing and thought to", "and thought to block", "thought to block midline", "to block midline re", "block midline re crossing", "re crossing chen", "crossing chen et", "chen et al. 2008", "et al. 2008 .", "al. 2008 . in", "2008 . in addition", ". in addition to", "in addition to slits", "to slits a", "slits a secreted", "a secreted ligand nell2", "secreted ligand nell2 also", "ligand nell2 also acts", "nell2 also acts as", "also acts as an", "acts as an axonal", "as an axonal guidance", "an axonal guidance cue", "axonal guidance cue that", "cue that by", "that by acting", "by acting through robo3", "acting through robo3 receptors", "robo3 receptors helps", "receptors helps to", "helps to steer commissural", "to steer commissural axons", "steer commissural axons to", "commissural axons to the", "axons to the midline.", "to the midline. both", "the midline. both robo3.1", "midline. both robo3.1 and", "both robo3.1 and robo3.2", "robo3.1 and robo3.2 can", "and robo3.2 can bind", "robo3.2 can bind to", "can bind to a", "bind to a secreted", "to a secreted ligand", "a secreted ligand nell2.", "secreted ligand nell2. pre", "ligand nell2. pre crossing", "nell2. pre crossing commissural", "pre crossing commissural axons", "commissural axons which", "axons which express", "express robo3.1 are", "robo3.1 are repelled", "are repelled by nell2.", "repelled by nell2. post", "by nell2. post crossing", "nell2. post crossing axons", "crossing axons which", "which express robo3.2 are", "express robo3.2 are not", "robo3.2 are not repelled", "are not repelled by", "not repelled by nell2", "by nell2 jaworski", "nell2 jaworski et", "jaworski et al. 2015", "et al. 2015 .", "al. 2015 . .", "commissural axons project to the", "axons project to the floor", "project to the floor plate", "the floor plate attracted", "floor plate attracted by", "plate attracted by the", "attracted by the interaction of", "by the interaction of their", "the interaction of their dcc", "interaction of their dcc receptors", "of their dcc receptors with", "their dcc receptors with netrin", "dcc receptors with netrin 1", "with netrin 1 ntn1", "1 ntn1 produced", "ntn1 produced by floor", "produced by floor plate cells", "floor plate cells dickson", "plate cells dickson and", "cells dickson and gilestro", "and gilestro 2006 and", "gilestro 2006 and radial", "2006 and radial glia", "and radial glia dominici", "radial glia dominici et", "glia dominici et al.", "et al. 2017 varadarajan", "al. 2017 varadarajan et", "2017 varadarajan et al.", "varadarajan et al. 2017 .", "et al. 2017 . once", "al. 2017 . once an", "2017 . once an axon", ". once an axon enters", "once an axon enters the", "an axon enters the floor", "axon enters the floor plate", "the floor plate it", "floor plate it must", "plate it must be", "it must be efficiently expelled", "must be efficiently expelled on", "be efficiently expelled on the", "efficiently expelled on the contralateral", "expelled on the contralateral side.", "on the contralateral side. a", "the contralateral side. a switch", "contralateral side. a switch from", "side. a switch from attraction", "a switch from attraction to", "switch from attraction to repulsion", "from attraction to repulsion allows", "attraction to repulsion allows commissural", "to repulsion allows commissural axons", "repulsion allows commissural axons to", "allows commissural axons to enter", "commissural axons to enter and", "axons to enter and then", "to enter and then leave", "enter and then leave the", "and then leave the cns", "then leave the cns midline.", "leave the cns midline. based", "the cns midline. based on", "cns midline. based on studies", "midline. based on studies in", "based on studies in xenopus", "on studies in xenopus neurons", "studies in xenopus neurons and", "in xenopus neurons and by", "xenopus neurons and by yeast", "neurons and by yeast two", "and by yeast two hybrid", "by yeast two hybrid screens", "two hybrid screens it", "hybrid screens it is", "screens it is observed", "it is observed that the", "is observed that the attractive", "observed that the attractive response", "that the attractive response of", "the attractive response of axons", "attractive response of axons to", "response of axons to netrins", "of axons to netrins is", "axons to netrins is silenced", "to netrins is silenced by", "netrins is silenced by activation", "is silenced by activation of", "silenced by activation of robo.", "by activation of robo. slit", "activation of robo. slit bound", "of robo. slit bound robo", "robo. slit bound robo binds", "slit bound robo binds to", "bound robo binds to dcc", "binds to dcc preventing", "to dcc preventing it", "dcc 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by dickson and gilestro", "and gilestro 2006 .", "gilestro 2006 . two", "2006 . two transcript variants", ". two transcript variants of", "two transcript variants of robo3", "variants of robo3 robo3.1", "of robo3 robo3.1 and", "robo3 robo3.1 and robo3.2", "robo3.1 and robo3.2 are considered", "and robo3.2 are considered to", "robo3.2 are considered to play", "are considered to play different", "considered to play different roles", "to play different roles in", "play different roles in midline", "different roles in midline crossing.", "roles in midline crossing. robo3.1", "in midline crossing. robo3.1 is", "midline crossing. robo3.1 is expressed", "crossing. robo3.1 is expressed in", "robo3.1 is expressed in the", "is expressed in the pre", "expressed in the pre crossing", "in the pre crossing and", "the pre crossing and crossing", "pre crossing and crossing commissural", "crossing and crossing commissural axons", "crossing commissural axons while", "commissural axons while robo3.2", 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"four isoforms", "isoforms in", "in humans", "and rps6ka6", "and each", "each of", "of the", "the isoforms", "isoforms have", "have six", "six conserved", "conserved phosphorylation", "phosphorylation sites", "in rps6ka1", "these are", "are serine", "serine residues", "residues s221", "s363 and", "and s380", "s380 and", "and threonine", "threonine residues", "residues t359", "t573 and", "and t732", "t732 .", ". phosphorylation", "phosphorylation at", "at four", "four of", "of these", "these residues", "residues appears", "appears to", "to be", "be critically", "critically important", "important for", "for the", "the catalytic", "catalytic activity", "activity of", "of rsks:", "rsks: s221", "and t573", "rps6ka1 .
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rsks", "especially rsk2", "are highly", "highly expressed", "expressed in", "in brain", "brain regions", "regions with", "with high", "high synaptic", "synaptic activity.", "activity. rsk2", "rsk2 mutations", "mutations are", "are the", "the underlying", "underlying cause", "cause of", "of coffin", "coffin lowry", "lowry syndrome", "which is", "is characterized", "characterized by", "by cognitive", "cognitive impairment", "impairment and", "and skeletal", "skeletal anomalies", "zeniou et", "al. 2002", "2002 .", "ribosomal s6 kinase", "kinase rsk", "rsk has", "has four isoforms", "four isoforms in", "isoforms in humans", "humans rps6ka1", "rps6ka1 rsk1", "rps6ka2 rsk3", "rps6ka3 rsk2", "rsk2 and", "rps6ka6 rsk4", "and each of", "each of the", "of the isoforms", "the isoforms have", "isoforms have six", "have six conserved", "six conserved phosphorylation", "conserved phosphorylation sites", "sites in", "rps6ka1 these", "these are serine", "are serine residues", "serine residues s221", "s221 s363", "s363 and s380", "and s380 and", "s380 and threonine", "and threonine residues", "threonine residues t359", "t359 t573", "t573 and t732", "and t732 .", "t732 . phosphorylation", ". phosphorylation at", "phosphorylation at four", "at four of", "four of these", "of these residues", "these residues appears", "residues appears to", "appears to be", "to be critically", "be critically important", "critically important for", "important for the", "for the catalytic", "the catalytic activity", "catalytic activity of", "activity of rsks:", "of rsks: s221", "s363 s380", "s380 and t573", "t573 in", "in rps6ka1 .
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rsks", ".
rsks especially", "rsk2 are", "are highly expressed", "highly expressed in", "expressed in brain", "in brain regions", "brain regions with", "regions with high", "with high synaptic", "high synaptic activity.", "synaptic activity. rsk2", "activity. rsk2 mutations", "rsk2 mutations are", "mutations are the", "are the underlying", "the underlying cause", "underlying cause of", "cause of coffin", "of coffin lowry", "coffin lowry syndrome", "syndrome cls", "which is characterized", "is characterized by", "characterized by cognitive", "by cognitive impairment", "cognitive impairment and", "impairment and skeletal", "and skeletal anomalies", "anomalies zeniou", "zeniou et al.", "et al. 2002", "al. 2002 .", "s6 kinase rsk", "rsk has four", "has four isoforms in", "four isoforms in humans", "in humans rps6ka1", "rsk1 rps6ka2", "rsk3 rps6ka3", "rsk2 and rps6ka6", "and rps6ka6 rsk4", "rsk4 and", "and each of the", "each of the isoforms", "of the isoforms have", "the isoforms have six", "isoforms have six conserved", "have six conserved phosphorylation", "six conserved phosphorylation sites", "phosphorylation sites in", "sites in rps6ka1", "in rps6ka1 these", "rps6ka1 these are", "these are serine residues", "are serine residues s221", "residues s221 s363", "s221 s363 and", "s363 and s380 and", "and s380 and threonine", "s380 and threonine residues", "and threonine residues t359", "residues t359 t573", "t359 t573 and", "t573 and t732 .", "and t732 . phosphorylation", "t732 . phosphorylation at", ". phosphorylation at four", "phosphorylation at four of", "at four of these", "four of these residues", "of these residues appears", "these residues appears to", "residues appears to be", "appears to be critically", "to be critically important", "be critically important for", "critically important for the", "important for the catalytic", "for the catalytic activity", "the catalytic activity of", "catalytic activity of rsks:", "activity of rsks: s221", "rsks: s221 s363", "s363 s380 and", "and t573 in", "t573 in rps6ka1", "in rps6ka1 .
phosphorylation and", "rps6ka1 .
phosphorylation and activation", ".
phosphorylation and activation of", "and activation of rsks", "activation of rsks primarily", "of rsks primarily occurs", "rsks primarily occurs at", "primarily occurs at the", "occurs at the plasma", "at the plasma membrane", "plasma membrane but", "membrane but can", "but can occur in", "can occur in the", "occur in the cytoplasm", "in the cytoplasm and", "the cytoplasm and in", "cytoplasm and in the", "and in the nucleus.", "in the nucleus. erks", "nucleus. erks mapk1", "erks mapk1 and", "mapk3 activated", "activated downstream of ras", "downstream of ras signaling", "ras signaling phosphorylate", "signaling phosphorylate rsks", "phosphorylate rsks on threonine", "rsks on threonine and", "on threonine and serine", "threonine and serine residues", "and serine residues t359", "residues t359 s363", "t359 s363 and", "in rps6ka1 . phosphorylation", "rps6ka1 . phosphorylation by", ". phosphorylation by erks", "phosphorylation by erks enables", "by erks enables autophosphorylation", "erks enables autophosphorylation of", "enables autophosphorylation of rsks", "autophosphorylation of rsks on", "of rsks on serine", "rsks on serine residue", "on serine residue s380", "serine residue s380 and", "residue s380 and threonine", "s380 and threonine residue", "and threonine residue t732", "residue t732 in", "t732 in rps6ka1", "rps6ka1 . phosphorylation of", ". phosphorylation of rsks", "phosphorylation of rsks by", "of rsks by pdpk1", "by pdpk1 pdk1", "pdk1 at serine", "at serine residue s221", "residue s221 in", "s221 in rps6ka1", "in rps6ka1 is", "rps6ka1 is necessary", "is necessary for the", "necessary for the full", "for the full activation", "the full activation of", "full activation of rsks", "activation of rsks and", "of rsks and phosphorylation", "rsks and phosphorylation of", "and phosphorylation of rsk", "phosphorylation of rsk substrates", "rsk substrates reviewed", "substrates reviewed by", "reviewed by anjum and", "by anjum and blenis", "anjum and blenis 2012", "and blenis 2012 .", "blenis 2012 . rsk4", "2012 . rsk4 differs", ". rsk4 differs from", "rsk4 differs from other", "differs from other rsks", "from other rsks because", "other rsks because it", "rsks because it shows", "because it shows high", "it shows high level", "shows high level of", "high level of constitutive", "level of constitutive phosphorylation", "of constitutive phosphorylation and", "constitutive phosphorylation and activity", "phosphorylation and activity in", "and activity in the", "activity in the absence", "in the absence of", "the absence of growth", "absence of growth factors", "growth factors although", "factors although it", "although it is still", "it is still responsive", "is still responsive to", "still responsive to growth", "responsive to growth factors", "to growth factors and", "growth factors and erk", "factors and erk activity", "erk activity dummler", "activity dummler et", "dummler et al. 2005", "et al. 2005 .
rsks", "2005 .
rsks especially", ".
rsks especially rsk2", "especially rsk2 are", "rsk2 are highly", "are highly expressed in", "highly expressed in brain", "expressed in brain regions", "in brain regions with", "brain regions with high", "regions with high synaptic", "with high synaptic activity.", "high synaptic activity. rsk2", "synaptic activity. rsk2 mutations", "activity. rsk2 mutations are", "rsk2 mutations are the", "mutations are the underlying", "are the underlying cause", "the underlying cause of", "underlying cause of coffin", "cause of coffin lowry", "of coffin lowry syndrome", "lowry syndrome cls", "cls which", "which is characterized by", "is characterized by cognitive", "characterized by cognitive impairment", "by cognitive impairment and", "cognitive impairment and skeletal", "impairment and skeletal anomalies", "skeletal anomalies zeniou", "anomalies zeniou et", "zeniou et al. 2002", "et al. 2002 .", "ribosomal s6 kinase rsk", "kinase rsk has", "rsk has four isoforms", "has four isoforms in humans", "isoforms in humans rps6ka1", "humans rps6ka1 rsk1", "rps6ka3 rsk2 and", "rsk4 and each", "and each of the isoforms", "each of the isoforms have", "of the isoforms have six", "the isoforms have six conserved", "isoforms have six conserved phosphorylation", "have six conserved phosphorylation sites", "conserved phosphorylation sites in", "phosphorylation sites in rps6ka1", "in rps6ka1 these are", "rps6ka1 these are serine", "these are serine residues s221", "serine residues s221 s363", "residues s221 s363 and", "s221 s363 and s380", "s363 and s380 and threonine", "and s380 and threonine residues", "s380 and threonine residues t359", "threonine residues t359 t573", "residues t359 t573 and", "t359 t573 and t732", "t573 and t732 . phosphorylation", "and t732 . phosphorylation at", "t732 . phosphorylation at four", ". phosphorylation at four of", "phosphorylation at four of these", "at four of these residues", "four of these residues appears", "of these residues appears to", "these residues appears to be", "residues appears to be critically", "appears to be critically important", "to be critically important for", "be critically important for the", "critically important for the catalytic", "important for the catalytic activity", "for the catalytic activity of", "the catalytic activity of rsks:", "catalytic activity of rsks: s221", "of rsks: s221 s363", "s221 s363 s380", "s363 s380 and t573", "s380 and t573 in", "and t573 in rps6ka1", "t573 in rps6ka1 .
phosphorylation", "in rps6ka1 .
phosphorylation and activation", "rps6ka1 .
phosphorylation and activation of", ".
phosphorylation and activation of rsks", "and activation of rsks primarily", "activation of rsks primarily occurs", "of rsks primarily occurs at", "rsks primarily occurs at the", "primarily occurs at the plasma", "occurs at the plasma membrane", "the plasma membrane but", "plasma membrane but can", "membrane but can occur", "but can occur in the", "can occur in the cytoplasm", "occur in the cytoplasm and", "in the cytoplasm and in", "the cytoplasm and in the", "cytoplasm and in the nucleus.", "and in the nucleus. erks", "the nucleus. erks mapk1", "nucleus. erks mapk1 and", "erks mapk1 and mapk3", "and mapk3 activated", "mapk3 activated downstream", "activated downstream of ras signaling", "of ras signaling phosphorylate", "ras signaling phosphorylate rsks", "signaling phosphorylate rsks on", "phosphorylate rsks on threonine and", "rsks on threonine and serine", "on threonine and serine residues", "threonine and serine residues t359", "serine residues t359 s363", "residues t359 s363 and", "t359 s363 and t573", "s363 and t573 in", "t573 in rps6ka1 .", "in rps6ka1 . phosphorylation by", "rps6ka1 . phosphorylation by erks", ". phosphorylation by erks enables", "phosphorylation by erks enables autophosphorylation", "by erks enables autophosphorylation of", "erks enables autophosphorylation of rsks", "enables autophosphorylation of rsks on", "autophosphorylation of rsks on serine", "of rsks on serine residue", "rsks on serine residue s380", "on serine residue s380 and", "serine residue s380 and threonine", "residue s380 and threonine residue", "s380 and threonine residue t732", "threonine residue t732 in", "residue t732 in rps6ka1", "t732 in rps6ka1 .", "in rps6ka1 . phosphorylation of", "rps6ka1 . phosphorylation of rsks", ". phosphorylation of rsks by", "phosphorylation of rsks by pdpk1", "rsks by pdpk1 pdk1", "pdpk1 pdk1 at", "pdk1 at serine residue", "serine residue s221 in", "residue s221 in rps6ka1", "in rps6ka1 is necessary", "rps6ka1 is necessary for", "is necessary for the full", "necessary for the full activation", "for the full activation of", "the full activation of rsks", "full activation of rsks and", "activation of rsks and phosphorylation", "of rsks and phosphorylation of", "rsks and phosphorylation of rsk", "and phosphorylation of rsk substrates", "of rsk substrates reviewed", "rsk substrates reviewed by", "substrates reviewed by anjum", "reviewed by anjum and blenis", "by anjum and blenis 2012", "anjum and blenis 2012 .", "and blenis 2012 . rsk4", "blenis 2012 . rsk4 differs", "2012 . rsk4 differs from", ". rsk4 differs from other", "rsk4 differs from other rsks", "differs from other rsks because", "from other rsks because it", "other rsks because it shows", "rsks because it shows high", "because it shows high level", "it shows high level of", "shows high level of constitutive", "high level of constitutive phosphorylation", "level of constitutive phosphorylation and", "of constitutive phosphorylation and activity", "constitutive phosphorylation and activity in", "phosphorylation and activity in the", "and activity in the absence", "activity in the absence of", "in the absence of growth", "the absence of growth factors", "of growth factors although", "growth factors although it", "factors although it is", "although it is still responsive", "it is still responsive to", "is still responsive to growth", "still responsive to growth factors", "responsive to growth factors and", "to growth factors and erk", "growth factors and erk activity", "and erk activity dummler", "erk activity dummler et", "activity dummler et al.", "dummler et al. 2005 .
rsks", "al. 2005 .
rsks especially", "2005 .
rsks especially rsk2", "especially rsk2 are highly", "rsk2 are highly expressed", "are highly expressed in brain", "highly expressed in brain regions", "expressed in brain regions with", "in brain regions with high", "brain regions with high synaptic", "regions with high synaptic activity.", "with high synaptic activity. rsk2", "high synaptic activity. rsk2 mutations", "synaptic activity. rsk2 mutations are", "activity. rsk2 mutations are the", "rsk2 mutations are the underlying", "mutations are the underlying cause", "are the underlying cause of", "the underlying cause of coffin", "underlying cause of coffin lowry", "cause of coffin lowry syndrome", "coffin lowry syndrome cls", "cls which is", "which is characterized by cognitive", "is characterized by cognitive impairment", "characterized by cognitive impairment and", "by cognitive impairment and skeletal", "cognitive impairment and skeletal anomalies", "and skeletal anomalies zeniou", "skeletal anomalies zeniou et", "anomalies zeniou et al.", "zeniou et al. 2002 ." ] }, { "record_id": "GLY_000594_1_981", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "446107", "r hsa", "hsa 446107", "r hsa 446107" ] }, { "record_id": "GLY_000594_1_981", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "type i", "i hemidesmosome", "hemidesmosome assembly", "type i hemidesmosome", "i hemidesmosome assembly", "type i hemidesmosome assembly", "are specialized", "specialized multiprotein", "multiprotein junctional", "junctional complexes", "complexes that", "that connect", "connect the", "the keratin", "keratin cytoskeleton", "cytoskeleton of", "of epithelial", "epithelial cells", "cells to", "to the", "the extracellular", "extracellular matrix", "matrix and", "and play", "play a", "a critical", "critical role", "in the", "the maintenance", "maintenance of", "of tissue", "tissue structure", "structure and", "and integrity", "reviewed in", "in litjens", "litjens et", "et al.", "2006 .", "hds mediate", "mediate adhesion", "adhesion of", "the underlying", "underlying basement", "basement membrane", "membrane in", "in stratified", "stratified squamous", "transitional and", "and pseudostratified", "pseudostratified epithelia", "jones et", "borradori and", "and sonnenberg", "1996 .", ". classical", "classical type", "i hds", "hds are", "are found", "found in", "stratified and", "and pseudo", "pseudo stratified", "stratified epithelia", "such as", "as the", "the skin", "and contain", "contain a6b4", "tetraspanin cd151", "cd151 and", "and the", "the bullous", "bullous pemphigoid", "antigens bp180", "bp180 and", "and bp230", ". while", "while hds", "hds function", "function in", "in promoting", "promoting stable", "stable adhesion", "they are", "are highly", "highly dynamic", "dynamic structures", "structures that", "are able", "able to", "to disassemble", "disassemble quickly", "for example", "during cell", "cell division", "or migration", "see margadant", "margadant et", "et al", "2008 .", "hemidesmosomes hds", "are specialized multiprotein", "specialized multiprotein junctional", "multiprotein junctional complexes", "junctional complexes that", "complexes that connect", "that connect the", "connect the keratin", "the keratin cytoskeleton", "keratin cytoskeleton of", "cytoskeleton of epithelial", "of epithelial cells", "epithelial cells to", "cells to the", "to the extracellular", "the extracellular matrix", "extracellular matrix and", "matrix and play", "and play a", "play a critical", "a critical role", "role in", "in the maintenance", "the maintenance of", "maintenance of tissue", "of tissue structure", "tissue structure and", "structure and integrity", "integrity reviewed", "reviewed in litjens", "in litjens et", "litjens et al.", "al. 2006", ". hds", "hds mediate adhesion", "mediate adhesion of", "adhesion of epithelial", "to the underlying", "the underlying basement", "underlying basement membrane", "basement membrane in", "membrane in stratified", "in stratified squamous", "squamous transitional", "transitional and pseudostratified", "and pseudostratified epithelia", "epithelia jones", "jones et al.", "al. 1994", "borradori and sonnenberg", "sonnenberg 1996", "1996 . classical", ". classical type", "classical type i", "type i hds", "i hds are", "hds are found", "are found in", "found in stratified", "in stratified and", "stratified and pseudo", "and pseudo stratified", "pseudo stratified epithelia", "epithelia such", "such as the", "as the skin", "skin and", "and contain a6b4", "a6b4 plectin", "plectin tetraspanin", "tetraspanin cd151 and", "cd151 and the", "and the bullous", "the bullous pemphigoid", "pemphigoid bp", "bp antigens", "antigens bp180 and", "bp180 and bp230", "bp230 reviewed", "2006 . while", ". while hds", "while hds function", "hds function in", "function in promoting", "in promoting stable", "promoting stable adhesion", "adhesion they", "they are highly", "are 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"found in stratified and", "in stratified and pseudo", "stratified and pseudo stratified", "and pseudo stratified epithelia", "stratified epithelia such", "epithelia such as", "such as the skin", "the skin and", "skin and contain", "contain a6b4 plectin", "plectin tetraspanin cd151", "tetraspanin cd151 and the", "cd151 and the bullous", "and the bullous pemphigoid", "bullous pemphigoid bp", "bp antigens bp180", "antigens bp180 and bp230", "and bp230 reviewed", "bp230 reviewed in", "2006 . while hds", ". while hds function", "while hds function in", "hds function in promoting", "function in promoting stable", "in promoting stable adhesion", "stable adhesion they", "adhesion they are", "they are highly dynamic", "are highly dynamic structures", "highly dynamic structures that", "structures that are", "that are able", "are able to disassemble", "able to disassemble quickly", "disassemble quickly for", "quickly for example", "for example during", "example during cell", "cell division differentiation", "differentiation or migration", "or migration see", "migration see margadant", "see margadant et al", "et al 2008", "al 2008 .", "hemidesmosomes hds are", "hds are specialized multiprotein", "are specialized multiprotein junctional complexes", "specialized multiprotein junctional complexes that", "multiprotein junctional complexes that connect", "junctional complexes that connect the", "complexes that connect the keratin", "that connect the keratin cytoskeleton", "connect the keratin cytoskeleton of", "the keratin cytoskeleton of epithelial", "keratin cytoskeleton of epithelial cells", "cytoskeleton of epithelial cells to", "of epithelial cells to the", "epithelial cells to the extracellular", "cells to the extracellular matrix", "to the extracellular matrix and", "the extracellular matrix and play", "extracellular matrix and play a", "matrix and play a critical", "and play a critical role", "a critical role in", "critical role in the", "role in the maintenance", "in 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and sonnenberg 1996", "and sonnenberg 1996 .", "sonnenberg 1996 . classical", "1996 . classical type i", ". classical type i hds", "classical type i hds are", "type i hds are found", "i hds are found in", "hds are found in stratified", "are found in stratified and", "found in stratified and pseudo", "in stratified and pseudo stratified", "stratified and pseudo stratified epithelia", "pseudo stratified epithelia such", "stratified epithelia such as", "epithelia such as the", "as the skin and", "the skin and contain", "skin and contain a6b4", "and contain a6b4 plectin", "a6b4 plectin tetraspanin", "plectin tetraspanin cd151 and", "tetraspanin cd151 and the bullous", "cd151 and the bullous pemphigoid", "the bullous pemphigoid bp", "pemphigoid bp antigens", "bp antigens bp180 and", "bp180 and bp230 reviewed", "and bp230 reviewed in", "bp230 reviewed in litjens", "al. 2006 . while", "2006 . while hds function", ". while hds function in", "while hds function in promoting", "hds function in 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"glycan precursor", "dolichol lipid", "lipid linked", "linked oligosaccharide", "and transfer", "transfer to", "to a", "a nascent", "nascent protein", "biosynthesis of the", "of the n", "the n glycan", "n glycan precursor", "precursor dolichol", "dolichol lipid linked", "lipid linked oligosaccharide", "oligosaccharide llo", "llo and", "and transfer to", "transfer to a", "to a nascent", "a nascent protein", "biosynthesis of the n", "of the n glycan", "the n glycan precursor", "glycan precursor dolichol", "precursor dolichol lipid", "dolichol lipid linked oligosaccharide", "linked oligosaccharide llo", "llo and transfer", "and transfer to a", "transfer to a nascent", "to a nascent protein", "biosynthesis of the n glycan", "of the n glycan precursor", "n glycan precursor dolichol", "glycan precursor dolichol lipid", "precursor dolichol lipid linked", "lipid linked oligosaccharide llo", "oligosaccharide llo and", "llo and transfer to", "and transfer to a nascent", "transfer to a nascent 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"release brough", "brough et al.", "et al. 2003", "al. 2003 .", "2003 . it", ". it has", "it has been", "has been reported", "been reported that", "reported that in", "that in monocytes", "in monocytes a", "monocytes a fraction", "a fraction of", "fraction of cellular", "of cellular il1b", "cellular il1b is", "il1b is released", "is released by", "released by the", "by the regulated", "the regulated secretion", "regulated secretion of", "secretion of late", "of late endosomes", "late endosomes and", "endosomes and early", "and early lysosomes", "lysosomes and", "and that this", "that this may", "this may represent", "may represent a", "represent a cellular", "a cellular compartment", "cellular compartment where", "compartment where caspase", "where caspase 1", "caspase 1 processing", "1 processing of", "pro il1b takes", "il1b takes place", "place andrei", "andrei et al.", "et al. 1999", "al. 1999 .", "1999 . shedding", ". shedding of", "shedding of microvesicles", "of microvesicles from", "microvesicles from the", "from the plasma", "the plasma membrane", "plasma membrane has", "membrane has also", "has also been", "also been proposed", "been proposed as", "proposed as a", "as a mechanism", "a mechanism of", "mechanism of secretion", "secretion mackenzie", "mackenzie et al.", "et al. 2001", "al. 2001 .", "2001 . these", ". these proposals", "these proposals superceded", "proposals superceded previous", "superceded previous models", "previous models in", "models in which", "in which non", "which non specific", "non specific release", "specific release due", "release due to", "due to cell", "to cell lysis", "cell lysis and", "lysis and passage", "and passage through", "passage through a", "through a plasma", "a plasma membrane", "plasma membrane pore", "membrane pore were", "pore were considered.", "were considered. however", "however there", "there is evidence", "is evidence in", "evidence in the", "in the literature", "the literature that", "literature that supports", "that supports all", "supports all of", "all of these", "of these mechanisms", "these mechanisms and", "mechanisms and there", "and there is", "there is still", "is still controversy", "still controversy over", "controversy over how", "over how il1b", "how il1b exits", "il1b exits from", "exits from cells", "cells brough", "brough & rothwell", "& rothwell 2007", "rothwell 2007 .", "2007 . a", ". a calpain", "a calpain like", "calpain like potease", "like potease has", "potease has been", "been reported to", "reported to be", "to be important", "be important for", "important for the", "for the processing", "the processing of", "il1a but", "but much less", "much less is", "less is known", "is known about", "known about how", "about how il1a", "how il1a is", "il1a is released", "is released from", "released from cells", "from cells and", "cells and what", "and what specific", "what specific roles", "specific roles it", "roles it plays", "it plays in", "plays in biology.", "the 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il1a", "pathway. il1a and", "il1a and il1b are", "and il1b are synthesised", "il1b are synthesised as", "are synthesised as cytoplasmic", "synthesised as cytoplasmic precursors", "cytoplasmic precursors pro", "precursors pro il1a", "pro il1a and pro", "il1a and pro il1b", "pro il1b in", "il1b in activated", "in activated cells. they", "activated cells. they have", "cells. they have no", "they have no signal", "have no signal sequence", "signal sequence precluding", "sequence precluding secretion", "precluding secretion via the", "secretion via the classical", "via the classical er", "the classical er golgi", "classical er golgi route", "golgi route rubartelli", "route rubartelli et", "rubartelli et al. 1990", "et al. 1990 .", "al. 1990 . processing", "1990 . processing of", ". processing of pro", "processing of pro il1b", "of pro il1b to", "pro il1b to the", "il1b to the active", "to the active form", "the active form requires", "active form requires caspase", "form requires caspase 1", "caspase 1 thornberry", "1 thornberry et", "thornberry et al. 1992", "1992 which", "which is itself activated", "is itself activated by", "itself activated by a", "activated by a molecular", "by a molecular scaffold", "a molecular scaffold termed", "molecular scaffold termed the", "scaffold termed the inflammasome", "the inflammasome martinon", "inflammasome martinon et", "martinon et al. 2002", "et al. 2002 .", "al. 2002 . processing", "2002 . processing and", ". processing and release", "processing and release of", "and release of il1b", "release of il1b are", "of il1b are thought", "il1b are thought to", "are thought to be", "thought to be closely", "to be closely linked", "closely linked because", "linked because mature", "because mature il1b is", "mature il1b is only", "il1b is only seen", "is only seen inside", "only seen inside inflammatory", "seen inside inflammatory cells", "inside inflammatory cells just", "inflammatory cells just prior", "cells just prior to", "just prior to release", "to release brough", "release brough et", "brough et al. 2003", "et al. 2003 .", "al. 2003 . it", "2003 . it has", ". it has been", "it has been reported", "has been reported that", "been reported that in", "reported that in monocytes", "that in monocytes a", "in monocytes a fraction", "monocytes a fraction of", "a fraction of cellular", "fraction of cellular il1b", "of cellular il1b is", "cellular il1b is released", "il1b is released by", "is released by the", "released by the regulated", "by the regulated secretion", "the regulated secretion of", "regulated secretion of late", "secretion of late endosomes", "of late endosomes and", "late endosomes and early", "endosomes and early lysosomes", "early lysosomes and", "lysosomes and that", "and that this may", "that this may represent", "this may represent a", "may represent a cellular", "represent a cellular compartment", "a cellular compartment where", "cellular compartment where caspase", "compartment where caspase 1", "where caspase 1 processing", "caspase 1 processing of", "1 processing of pro", "of pro il1b takes", "pro il1b takes place", "takes place andrei", "place andrei et", "andrei et al. 1999", "et al. 1999 .", "al. 1999 . shedding", "1999 . shedding of", ". shedding of microvesicles", "shedding of microvesicles from", "of microvesicles from the", "microvesicles from the plasma", "from the plasma membrane", "the plasma membrane has", "plasma membrane has also", "membrane has also been", "has also been proposed", "also been proposed as", "been proposed as a", "proposed as a mechanism", "as a mechanism of", "a mechanism of secretion", "of secretion mackenzie", "secretion mackenzie et", "mackenzie et al. 2001", "et al. 2001 .", "al. 2001 . these", "2001 . these proposals", ". these proposals superceded", "these proposals superceded previous", "proposals superceded previous models", "superceded previous models in", "previous models in which", "models in which non", "in which non specific", "which non specific release", "non specific release due", "specific release due to", "release due to cell", "due to cell lysis", "to cell lysis and", "cell lysis and passage", "lysis and passage through", "and passage through a", "passage through a plasma", "through a plasma membrane", "a plasma membrane pore", "plasma membrane pore were", "membrane pore were considered.", "pore were considered. however", "considered. however there", "however there is", "there is evidence in", "is evidence in the", "evidence in the literature", "in the literature that", "the literature that supports", "literature that supports all", "that supports all of", "supports all of these", "all of these mechanisms", "of these mechanisms and", "these mechanisms and there", "mechanisms and there is", "and there is still", "there is still controversy", "is still controversy over", "still controversy over how", "controversy over how il1b", "over how il1b exits", "how il1b exits from", "il1b exits from cells", "from cells brough", "cells brough &", "brough & rothwell 2007", "& rothwell 2007 .", "rothwell 2007 . a", "2007 . a calpain", ". a calpain like", "a calpain like potease", "calpain like potease has", "like potease has been", "potease has been reported", "has been reported to", "been reported to be", "reported to be important", "to be important for", "be important for the", "important for the processing", "for the processing of", "of pro il1a", "pro il1a but", "il1a but much", "but much less is", "much less is known", "less is known about", "is known about how", "known about how il1a", "about how il1a is", "how il1a is released", "il1a is released from", "is released from cells", "released from cells and", "from cells and what", "cells and what specific", "and what specific roles", "what specific roles it", "specific roles it plays", "roles it plays in", "it plays in biology.", "the il 1 family of", "il 1 family of cytokines", "1 family of cytokines that", "family of cytokines that interact", "of cytokines that interact with", "cytokines that interact with the", "that interact with the type", "interact with the type 1", "with the type 1 il", "the type 1 il 1r", "type 1 il 1r include", "1 il 1r include il", "il 1r include il 1\u03b1", "include il 1\u03b1 il1a", "il1a il 1\u03b2", "1\u03b2 il1b and", "il1b and the il", "and the il 1 receptor", "the il 1 receptor antagonist", "il 1 receptor antagonist protein", "receptor antagonist protein il1rap", "antagonist protein il1rap .", "protein il1rap . il1rap", "il1rap . il1rap is synthesized", ". il1rap is synthesized with", "il1rap is synthesized with a", "is synthesized with a signal", "synthesized with a signal peptide", "with a signal peptide and", "a signal peptide and secreted", "signal peptide and secreted as", "peptide and secreted as a", "and secreted as a mature", "secreted as a mature protein", "as a mature protein via", "a mature protein via the", "mature protein via the classical", "protein via the classical secretory", "via the classical secretory pathway.", "classical secretory pathway. il1a", "secretory pathway. il1a and", "pathway. il1a and il1b", "il1a and il1b are synthesised", "and il1b are synthesised as", "il1b are synthesised as cytoplasmic", "are synthesised as cytoplasmic precursors", "as cytoplasmic precursors pro", "cytoplasmic precursors pro il1a", "precursors pro il1a and", "pro il1a and pro il1b", "and pro il1b in", "pro il1b in activated", "il1b in activated cells.", "in activated cells. they have", "activated cells. they have no", "cells. they have no signal", "they have no signal sequence", "no signal sequence precluding", "signal sequence precluding secretion", "sequence precluding secretion via", "precluding secretion via the classical", "secretion via the classical er", "via the classical er golgi", "the classical er golgi route", "er golgi route rubartelli", "golgi route rubartelli et", "route rubartelli et al.", "rubartelli et al. 1990 .", "et al. 1990 . processing", "al. 1990 . processing of", "1990 . processing of pro", ". processing of pro il1b", "processing of pro il1b to", "of pro il1b to the", "pro il1b to the active", "il1b to the active form", "to the active form requires", "the active form requires caspase", "active form requires caspase 1", "requires caspase 1 thornberry", "caspase 1 thornberry et", "1 thornberry et al.", "al. 1992 which", "1992 which is", "which is itself activated by", "is itself activated by a", "itself activated by a molecular", "activated by a molecular scaffold", "by a molecular scaffold termed", "a molecular scaffold termed the", "molecular scaffold termed the inflammasome", "termed the inflammasome martinon", "the inflammasome martinon et", "inflammasome martinon et al.", "martinon et al. 2002 .", "et al. 2002 . processing", "al. 2002 . processing and", "2002 . processing and release", ". processing and release of", "processing and release of il1b", "and release of il1b are", "release of il1b are thought", "of il1b are thought to", "il1b are thought to be", "are thought to be closely", "thought to be closely linked", "be closely linked because", "closely linked because mature", "linked because mature il1b", "because mature il1b is only", "mature il1b is only seen", "il1b is only seen inside", "is only seen inside inflammatory", "only seen inside inflammatory cells", "seen inside inflammatory cells just", "inside inflammatory cells just prior", "inflammatory cells just prior to", "cells just prior to release", "prior to release brough", "to release brough et", "release brough et al.", "brough et al. 2003 .", "et al. 2003 . it", "al. 2003 . it has", "2003 . it has been", ". it has been reported", "it has been reported that", "has been reported that in", "been reported that in monocytes", "reported that in monocytes a", "that in monocytes a fraction", "in monocytes a fraction of", "monocytes a fraction of cellular", "a fraction of cellular il1b", "fraction of cellular il1b is", "of cellular il1b is released", "cellular il1b is released by", "il1b is released by the", "is released by the regulated", "released by the regulated secretion", "by the regulated secretion of", "the regulated secretion of late", "regulated secretion of late endosomes", "secretion of late endosomes and", "of late endosomes and early", "late endosomes and early lysosomes", "and early lysosomes and", "early lysosomes and that", "lysosomes and that this", "and that this may represent", "that this may represent a", "this may represent a cellular", "may represent a cellular compartment", "represent a cellular compartment where", "a cellular compartment where caspase", "cellular compartment where caspase 1", "compartment where caspase 1 processing", "where caspase 1 processing of", "caspase 1 processing of pro", "1 processing of pro il1b", "processing of pro il1b takes", "of pro il1b takes place", "il1b takes place andrei", "takes place andrei et", "place andrei et al.", "andrei et al. 1999 .", "et al. 1999 . shedding", "al. 1999 . shedding of", "1999 . shedding of microvesicles", ". shedding of microvesicles from", "shedding of microvesicles from the", "of microvesicles from the plasma", "microvesicles from the plasma membrane", "from the plasma membrane has", "the plasma membrane has also", "plasma membrane has also been", "membrane has also been proposed", "has also been proposed as", "also been proposed as a", "been proposed as a mechanism", "proposed as a mechanism of", "as a mechanism of secretion", "mechanism of secretion mackenzie", "of secretion mackenzie et", "secretion mackenzie et al.", "mackenzie et al. 2001 .", "et al. 2001 . these", "al. 2001 . these proposals", "2001 . these proposals superceded", ". these proposals superceded previous", "these proposals superceded previous models", "proposals superceded previous models in", "superceded previous models in which", "previous models in which non", "models in which non specific", "in which non specific 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"essential part of the immune", "part of the immune system." ] }, { "record_id": "GLY_000594_1_987", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450302", "r hsa", "hsa 450302", "r hsa 450302" ] }, { "record_id": "GLY_000594_1_987", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated tak1", "tak1 mediates", "mediates p38", "p38 mapk", "mapk activation", "activated tak1 mediates", "tak1 mediates p38", "mediates p38 mapk", "p38 mapk activation", "activated tak1 mediates p38", "tak1 mediates p38 mapk", "mediates p38 mapk activation", "activated tak1 mediates p38 mapk", "tak1 mediates p38 mapk activation", "p38 mitogen", "mitogen activated", "activated protein", "protein kinase", "belongs to", "to a", "a highly", "highly conserved", "conserved family", "family of", "of serine/threonine", "serine/threonine protein", "protein kinases.", "kinases.

the", "

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the p38 mapk dependent signaling", "p38 mapk dependent signaling cascade", "mapk dependent signaling cascade is", "dependent signaling cascade is activated", "signaling cascade is activated by", "cascade is activated by pro", "is activated by pro inflammatory", "activated by pro inflammatory or", "by pro inflammatory or stressful", "pro inflammatory or stressful stimuli", "inflammatory or stressful stimuli such", "or stressful stimuli such as", "stressful stimuli such as ultraviolet", "stimuli such as ultraviolet radiation", "as ultraviolet radiation oxidative", "ultraviolet radiation oxidative injury", "oxidative injury heat shock", "shock cytokines and", "cytokines and other pro", "and other pro inflammatory stimuli.", "other pro inflammatory stimuli. p38", "pro inflammatory stimuli. p38 mapk", "inflammatory stimuli. p38 mapk exists", "stimuli. p38 mapk exists as", "p38 mapk exists as four", "mapk exists as four isoforms", "as four isoforms alpha", "isoforms alpha beta", "alpha beta gamma", "beta gamma and", "gamma and delta .", "and delta . of these", ". of these p38alpha", "of these p38alpha and", "these p38alpha and p38beta", "p38alpha and p38beta are ubiquitously", "and p38beta are ubiquitously expressed", "p38beta are ubiquitously expressed while", "are ubiquitously expressed while p38gamma", "ubiquitously expressed while p38gamma and", "expressed while p38gamma and p38delta", "while p38gamma and p38delta are", "p38gamma and p38delta are differentially", "and p38delta are differentially expressed", "p38delta are differentially expressed depending", "are differentially expressed depending on", "differentially expressed depending on tissue", "expressed depending on tissue type.", "depending on tissue type. each", "on tissue type. each isoform", "tissue type. each isoform is", "type. each isoform is activated", "each isoform is activated by", "isoform is activated by upstream", "is activated by upstream kinases", "activated by upstream kinases including", "by upstream kinases including map", "upstream kinases including map kinase", "kinases including map kinase kinases", "map kinase kinases mkk", "kinases mkk 3", "mkk 3 4", "3 4 and", "and 6 which in", "6 which in turn", "which in turn are phosphorylated", "in turn are phosphorylated by", "turn are phosphorylated by activated", "phosphorylated by activated tak1", "by activated tak1 at", "activated tak1 at the", "tak1 at the typical ser", "at the typical ser xaa", "the typical ser xaa ala", "typical ser xaa ala xaa", "ser xaa ala xaa thr", "xaa ala xaa thr motif", "ala xaa thr motif in", "xaa thr motif in their", "thr motif in their activation", "motif in their activation loops.

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          ap 1 activity", "assembly.

          ap 1 activity is", "

          ap 1 activity is regulated", "1 activity is regulated on", "activity is regulated on multiple", "is regulated on multiple levels", "on multiple levels transcriptional", "levels transcriptional translational", "transcriptional translational and post", "translational and post translational control", "and post translational control mechanisms", "post translational control mechanisms contribute", "translational control mechanisms contribute to", "control mechanisms contribute to the", "mechanisms contribute to the balanced", "contribute to the balanced production", "to the balanced production of", "the balanced production of ap", "balanced production of ap 1", "production of ap 1 proteins", "of ap 1 proteins and", "ap 1 proteins and their", "1 proteins and their functions.", "proteins and their functions. briefly", "their functions. briefly regulation", "functions. briefly regulation occurs", "briefly regulation occurs through:

          1. effects", "regulation occurs through:
            1. effects on jun", "through:
              1. effects on jun fos", "jun fos atf", "fos atf gene transcription", "atf gene transcription and mrna", "gene transcription and mrna turnover.
              2. ", "transcription and mrna turnover.
              3. ap", "and mrna turnover.
              4. ap 1", "mrna turnover.
              5. ap 1 protein", "turnover.
              6. ap 1 protein members", "ap 1 protein members turnover.", "1 protein members turnover.
              7. post", "protein members turnover.
              8. post translational", "members turnover.
              9. post translational modifications", "turnover.
              10. post translational modifications of", "
              11. post translational modifications of ap", "translational modifications of ap 1", "modifications of ap 1 proteins", "of ap 1 proteins that", "ap 1 proteins that modulate", "1 proteins that modulate their", "proteins that modulate their transactivation", "that modulate their transactivation potential", "their transactivation potential effect", "transactivation potential effect of", "potential effect of protein", "effect of protein kinases or", "of protein kinases or phosphatases", "protein kinases or phosphatases .
              12. interactions", "kinases or phosphatases .
              13. interactions with", "or phosphatases .
              14. interactions with other", "phosphatases .
              15. interactions with other transcription", ".
              16. interactions with other transcription factors", "with other transcription factors that", "other transcription factors that can", "transcription factors that can either", "factors that can either induce", "that can either induce or", "can either induce or interfere", "either induce or interfere with", "induce or interfere with ap", "or interfere with ap 1", "interfere with ap 1 activity.
              " ] }, { "record_id": "GLY_000594_1_989", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450604", "r hsa", "hsa 450604", "r hsa 450604" ] }, { "record_id": "GLY_000594_1_989", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "binds and", "and destabilizes", "destabilizes mrna", "ksrp khsrp", "khsrp binds", "binds and destabilizes", "and destabilizes mrna", "khsrp binds and", "binds and destabilizes mrna", "ksrp khsrp binds", "khsrp binds and destabilizes", "ksrp binds", "binds to", "to au", "au rich", "rich sequences", "sequences in", "in the", "the 3'", "3' untranslated", "untranslated regions", "regions of", "of mrnas.", "mrnas. ksrp", "ksrp causes", "causes the", "the bound", "bound mrna", "mrna to", "to be", "be targeted", "targeted for", "for hydrolysis", "hydrolysis by", "by recruiting", "recruiting exonucleases", "exonucleases and", "and decapping", "decapping enzymes.", 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3zeta", "3zeta ywhaz", "ywhaz which", "which causes ksrp", "causes ksrp to", "ksrp to be", "to be retained", "be retained in", "retained in the", "in the nucleus.", "ksrp binds to au", "binds to au rich", "to au rich sequences", "au rich sequences in", "rich sequences in the", "sequences in the 3'", "in the 3' untranslated", "the 3' untranslated regions", "3' untranslated regions of", "untranslated regions of mrnas.", "regions of mrnas. ksrp", "of mrnas. ksrp causes", "mrnas. ksrp causes the", "ksrp causes the bound", "causes the bound mrna", "the bound mrna to", "bound mrna to be", "mrna to be targeted", "to be targeted for", "be targeted for hydrolysis", "targeted for hydrolysis by", "for hydrolysis by recruiting", "hydrolysis by recruiting exonucleases", "by recruiting exonucleases and", "recruiting exonucleases and decapping", "exonucleases and decapping enzymes.", "and decapping enzymes. the", "decapping enzymes. the activity", "enzymes. the activity of", "the activity of ksrp", 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"romeo et", "2012 .", ". they", "they are", "are a", "a major", "major cell", "cell type", "type in", "in the", "the inner", "inner cell", "cell mass", "mass of", "the early", "early embryo", "embryo in", "in vivo", "and cells", "cells with", "with the", "the same", "same properties", "induced pluripotent", "can be", "be generated", "generated in", "in vitro", "vitro from", "from differentiated", "differentiated adult", "adult cells", "cells by", "by overexpression", "overexpression of", "of a", "a set", "set of", "of transcription", "transcription factor", "factor genes", "takahashi and", "and yamanaka", "yamanaka 2006", "takahashi et", "yu et", "jaenisch and", "and young", "young 2008", "in dejosez", "dejosez and", "and zwaka", "zwaka 2012", "2012 .
              pluripotency", ".
              pluripotency is", "is maintained", "maintained by", "by a", "a self", "self reinforcing", "reinforcing loop", "loop of", "transcription factors", "boyer et", "al. 2005", "matoba et", "babaie et", "sun et", "al. 2008", "in kashyap", "kashyap et", ". in", "initiation of", "of pluripotency", "pluripotency may", "may depend", "depend on", "on maternal", "maternal factors", "factors transmitted", "transmitted through", "through the", "the oocyte", "and on", "on dna", "dna demethylation", "demethylation in", "the zygote", "recently reviewed", "in seisenberger", "seisenberger et", "and hypoxia", "hypoxia experienced", "experienced by", "by the", "the blastocyst", "blastocyst in", "the reproductive", "reproductive tract", "tract before", "before implantation", "forristal et", "al. 2010", "in mohyeldin", "mohyeldin et", "2010 .", "induced pluripotency", "may initiate", "initiate with", "with demethylation", "demethylation and", "and activation", "activation of", "the promoters", "promoters of", "of pou5f1", "and nanog", "bhutani et", ". hypoxia", "hypoxia also", "also significantly", "significantly enhances", "enhances conversion", "conversion to", "to pluripotent", "yoshida et", "2009 .", ". pou5f1", "pou5f1 and", "together with", "with sox2", "encode central", "central factors", "factors in", "in pluripotency", "pluripotency and", "and activate", "activate their", "their own", "own transcription", "al 2005", "2007 .", ". the", "the autoactivation", "autoactivation loop", "loop maintains", "maintains expression", "expression of", "and sox2", "sox2 at", "at high", "high levels", "levels in", "in stem", "cells and", "in turn", "complexes containing", "containing various", "various combinations", "combinations of", "of these", "these factors", "remenyi et", "al. 2003", "lam et", "activate the", "the expression", "a group", "group of", "of genes", "genes whose", "whose products", "products are", "are associated", "associated with", "with rapid", "rapid cell", "cell proliferation", "proliferation and", "and repress", "repress the", "with cell", "cell differentiation", "chavez et", "guenther 2011", "2011 .
              comparisons", ".
              comparisons between", "between human", "human and", "and mouse", "mouse embryonic", "embryonic stem", "cells must", "must be", "be made", "made with", "with caution", "caution and", "and for", "for this", "this reason", "reason inferences", "inferences from", "from mouse", "mouse have", "have been", "been used", "used sparingly", "sparingly in", "in this", "this module.", "module. human", "human escs", "escs more", "more closely", "closely resemble", "resemble mouse", "mouse epiblast", "epiblast stem", "cells in", "in having", "having inactivated", "inactivated x", "x chromosomes", "flattened morphology", "and intolerance", "intolerance to", "to passaging", "passaging as", "as single", "single cells", "hanna et", ". molecularly", "escs differ", "differ from", "mouse escs", "escs in", "in being", "being maintained", "by fgf", "fgf and", "and activin/nodal/tgfbeta", "activin/nodal/tgfbeta signaling", "signaling rather", "rather than", "than by", "by lif", "lif and", "and canonical", "canonical wnt", "wnt signaling", "greber et", "in katoh", "katoh 2011", "2011 .", "in human", "escs pou5f1", "pou5f1 binds", "binds and", "and directly", "directly activates", "activates the", "the fgf2", "fgf2 gene", "however pou5f1", "pou5f1 does", "does not", "not activate", "activate fgf2", "fgf2 in", "in mouse", "in de", "de los", "los angeles", "angeles et", ". differences", "differences in", "in expression", "expression patterns", "patterns of", "of klf2", "nodal were", "were observed", "observed between", "cai et", "as were", "were differences", "of eomes", "arnt and", "and several", "several other", "other genes", "ginis et", "et al.2004", "al.2004 .", "stem cells are", "cells are undifferentiated", "are undifferentiated cells", "undifferentiated cells posessing", "cells posessing an", "posessing an abbreviated", "an abbreviated cell", "abbreviated cell cycle", "cycle reviewed", "reviewed in stein", "in stein et", "stein et al.", "et al. 2012", "a characteristic profile", "characteristic profile of", "profile of gene", "of gene expression", "expression rao", "rao et al.", "et al. 2004", "2004 kim", "kim et al.", "et al. 2006", "2006 player", "player et al.", "2006 wang", "wang et al", "et al 2006", "al 2006 using", "2006 using mouse", "mouse international", "international stem cell", "stem cell initiative", "cell initiative 2007", "2007 assou", "assou et al.", "et al. 2007", "et al. 2009", "2009 ding", "ding et al.", "al. 2012 using", "2012 using mouse", "and the ability", "the ability to", "ability to self", "to self renew", "self renew and", "renew and generate", "and generate all", "generate all cell", "all cell types", "cell types of", "types of the", "of the body", "the body except", "body except extraembryonic", "except extraembryonic lineages", "lineages marti", "marti et al.", "et al. 2013", "2013 reviewed", "reviewed in romeo", "in romeo et", "romeo et al.", "al. 2012 .", "2012 . they", ". they are", "they are a", "are a major", "a major cell", "major cell type", "cell type in", "type in the", "in the inner", "the inner cell", "inner cell mass", "cell mass of", "mass of the", "of the early", "the early embryo", "early embryo in", "embryo in vivo", "vivo and", "and cells with", "cells with the", "with the same", "the same properties", "properties induced", "induced pluripotent stem", "cells can", "can be generated", "be generated in", "generated in vitro", "in vitro from", "vitro from differentiated", "from differentiated adult", "differentiated adult cells", "adult cells by", "cells by overexpression", "by overexpression of", "overexpression of a", "of a set", "a set of", "set of transcription", "of transcription factor", "transcription factor genes", "genes takahashi", "takahashi and yamanaka", "and yamanaka 2006", "2006 takahashi", "takahashi et al.", "2007 yu", "yu et al.", "2007 jaenisch", "jaenisch and young", "and young 2008", "2008 stein", "2012 reviewed", "reviewed in dejosez", "in dejosez and", "dejosez and zwaka", "and zwaka 2012", "zwaka 2012 .
              pluripotency", "2012 .
              pluripotency is", ".
              pluripotency is maintained", "is maintained by", "maintained by a", "by a self", "a self reinforcing", "self reinforcing loop", "reinforcing loop of", "loop of transcription", "of transcription factors", "factors boyer", "boyer et al.", "et al. 2005", "2005 rao", "2006 matoba", "matoba et al.", "2006 babaie", "babaie et al.", "2007 sun", "sun et al.", "et al. 2008", "2008 assou", "2009 reviewed", "reviewed in kashyap", "in kashyap et", "kashyap et al.", "zwaka 2012 .", "2012 . in", ". in vivo", "vivo initiation", "initiation of pluripotency", "of pluripotency may", "pluripotency may depend", "may depend on", "depend on maternal", "on maternal factors", "maternal factors transmitted", "factors transmitted through", "transmitted through the", "through the oocyte", "oocyte assou", "2009 and", "and on dna", "on dna demethylation", "dna demethylation in", "demethylation in the", "in the zygote", "zygote recently", "recently reviewed in", "reviewed in seisenberger", "in seisenberger et", "seisenberger et al.", "2013 and", "and hypoxia experienced", "hypoxia experienced by", "experienced by the", "by the blastocyst", "the blastocyst in", "blastocyst in the", "in the reproductive", "the reproductive tract", "reproductive tract before", "tract before implantation", "implantation forristal", "forristal et al.", "et al. 2010", "2010 reviewed", "reviewed in mohyeldin", "in mohyeldin et", "mohyeldin et al.", "al. 2010 .", "2010 . in", ". in vitro", "vitro induced", "induced pluripotency may", "pluripotency may initiate", "may initiate with", "initiate with demethylation", "with demethylation and", "demethylation and activation", "and activation of", "activation of the", "of the promoters", "the promoters of", "promoters of pou5f1", "pou5f1 oct4", "oct4 and", "nanog bhutani", "bhutani et al.", "2010 . hypoxia", ". hypoxia also", "hypoxia also significantly", "also significantly enhances", "significantly enhances conversion", "enhances conversion to", "conversion to pluripotent", "to pluripotent stem", "cells yoshida", "yoshida et al.", "al. 2009 .", "2009 . pou5f1", ". pou5f1 and", "pou5f1 and nanog", "nanog together", "together with sox2", "sox2 encode", "encode central factors", "central factors in", "factors in pluripotency", "in pluripotency and", "pluripotency and activate", "and activate their", "activate their own", "their own transcription", "transcription boyer", "boyer et al", "et al 2005", "2005 babaie", "2007 takahashi", "al. 2007 .", "2007 . the", ". the autoactivation", "the autoactivation loop", "autoactivation loop maintains", "loop maintains expression", "maintains expression of", "expression of pou5f1", "pou5f1 nanog", "nanog and", "and sox2 at", "sox2 at high", "at high levels", "high levels in", "levels in stem", "in stem cells", "stem cells and", "and in", "turn complexes", "complexes containing various", "containing various combinations", "various combinations of", "combinations of these", "of these factors", "factors remenyi", "remenyi et al.", "et al. 2003", "2003 lam", "lam et al.", "2012 activate", "activate the expression", "the expression of", "expression of a", "of a group", "a group of", "group of genes", "of genes whose", "genes whose products", "whose products are", "products are associated", "are associated with", "associated with rapid", "with rapid cell", "rapid cell proliferation", "cell proliferation and", "proliferation and repress", "and repress the", "repress the expression", "associated with cell", "with cell differentiation", "differentiation boyer", "2005 matoba", "2007 chavez", "chavez et al.", "2009 forristal", "2010 guenther", "guenther 2011 .
              comparisons", "2011 .
              comparisons between", ".
              comparisons between human", "between human and", "human and mouse", "and mouse embryonic", "mouse embryonic stem", "embryonic stem cells", "stem cells must", "cells must be", "must be made", "be made with", "made with caution", "with caution and", "caution and for", "and for this", "for this reason", "this reason inferences", "reason inferences from", "inferences from mouse", "from mouse have", "mouse have been", "have been used", "been used sparingly", "used sparingly in", "sparingly in this", "in this module.", "this module. human", "module. human escs", "human escs more", "escs more closely", "more closely resemble", "closely resemble mouse", "resemble mouse epiblast", "mouse epiblast stem", "epiblast stem cells", "stem cells in", "cells in having", "in having inactivated", "having inactivated x", "inactivated x chromosomes", "chromosomes flattened", "morphology and", "and intolerance to", "intolerance to passaging", "to passaging as", "passaging as single", "as single cells", "cells hanna", "hanna et al.", "2010 . molecularly", "molecularly human", "human escs differ", "escs differ from", "differ from mouse", "from mouse escs", "mouse escs in", "escs in being", "in being maintained", "being maintained by", "maintained by fgf", "by fgf and", "fgf and activin/nodal/tgfbeta", "and activin/nodal/tgfbeta signaling", "activin/nodal/tgfbeta signaling rather", "signaling rather than", "rather than by", "than by lif", "by lif and", "lif and canonical", "and canonical wnt", "canonical wnt signaling", "signaling greber", "greber et al.", "reviewed in katoh", "in katoh 2011", "katoh 2011 .", "2011 . in", ". in human", "in human escs", "human escs pou5f1", "escs pou5f1 binds", "pou5f1 binds and", "binds and directly", "and directly activates", "directly activates the", "activates the fgf2", "the fgf2 gene", "gene however", "however pou5f1 does", "pou5f1 does not", "does not activate", "not activate fgf2", "activate fgf2 in", "fgf2 in mouse", "in mouse escs", "escs reviewed", "reviewed in de", "in de los", "de los angeles", "los angeles et", "angeles et al.", "2012 . differences", ". differences in", "differences in expression", "in expression patterns", "expression patterns of", "patterns of klf2", "klf2 klf4", "klf4 klf5", "klf5 esrrb", "esrrb foxd3", "foxd3 socs3", "socs3 lin28", "lin28 nodal", "nodal were observed", "were observed between", "observed between human", "and mouse escs", "escs cai", "cai et al.", "2010 as", "as were differences", "were differences in", "in expression of", "expression of eomes", "eomes arnt", "arnt and several", "and several other", "several other genes", "genes ginis", "ginis et al.2004", "et al.2004 .", "pluripotent stem cells are", "stem cells are undifferentiated", "cells are undifferentiated cells", "are undifferentiated cells posessing", "undifferentiated cells posessing an", "cells posessing an abbreviated", "posessing an abbreviated cell", "an abbreviated cell cycle", "cell cycle reviewed", "cycle reviewed in", "reviewed in stein et", "in stein et al.", "stein et al. 2012", "2012 a", "a characteristic profile of", "characteristic profile of gene", "profile of gene expression", "gene expression rao", "expression rao et", "rao et al. 2004", "al. 2004 kim", "2004 kim et", "kim et al. 2006", "al. 2006 player", "2006 player et", "player et al. 2006", "al. 2006 wang", "2006 wang et", "wang et al 2006", "et al 2006 using", "al 2006 using mouse", "using mouse international", "mouse international stem", "international stem cell initiative", "stem cell initiative 2007", "initiative 2007 assou", "2007 assou et", "assou et al. 2007", "al. 2007 assou", "assou et al. 2009", "al. 2009 ding", "2009 ding et", "ding et al. 2012", "et al. 2012 using", "al. 2012 using mouse", "mouse and", "and the ability to", "the ability to self", "ability to self renew", "to self renew and", "self renew and generate", "renew and generate all", "and generate all cell", "generate all cell types", "all cell types of", "cell types of the", "types of the body", "of the body except", "the body except extraembryonic", "body except extraembryonic lineages", "extraembryonic lineages marti", "lineages marti et", "marti et al. 2013", "al. 2013 reviewed", "2013 reviewed in", "reviewed in romeo et", "in romeo et al.", "romeo et al. 2012", "et al. 2012 .", "al. 2012 . they", "2012 . they are", ". they are a", "they are a major", "are a major cell", "a major cell type", "major cell type in", "cell type in the", "type in the inner", "in the inner cell", "the inner cell mass", "inner cell mass of", "cell mass of the", "mass of the early", "of the early embryo", "the early embryo in", "early embryo in vivo", "in vivo and", "vivo and cells", "and cells with the", "cells with the same", "with the same properties", "same properties induced", "properties induced pluripotent", "induced pluripotent stem cells", "stem cells can", "cells can be", "can be generated in", "be generated in vitro", "generated in vitro from", "in vitro from differentiated", "vitro from differentiated adult", "from differentiated adult cells", "differentiated adult cells by", "adult cells by overexpression", "cells by overexpression of", "by overexpression of a", "overexpression of a set", "of a set of", "a set of transcription", "set of transcription factor", "of transcription factor genes", "factor genes takahashi", "genes takahashi and", "takahashi and yamanaka 2006", "yamanaka 2006 takahashi", "2006 takahashi et", "takahashi et al. 2007", "al. 2007 yu", "2007 yu et", "yu et al. 2007", "al. 2007 jaenisch", "2007 jaenisch and", "jaenisch and young 2008", "young 2008 stein", "2008 stein et", "al. 2012 reviewed", "2012 reviewed in", "reviewed in dejosez and", "in dejosez and zwaka", "dejosez and zwaka 2012", "and zwaka 2012 .
              pluripotency", "zwaka 2012 .
              pluripotency is", "2012 .
              pluripotency is maintained", ".
              pluripotency is maintained by", "is maintained by a", "maintained by a self", "by a self reinforcing", "a self reinforcing loop", "self reinforcing loop of", "reinforcing loop of transcription", "loop of transcription factors", "transcription factors boyer", "factors boyer et", "boyer et al. 2005", "al. 2005 rao", "2005 rao et", "rao et al. 2006", "al. 2006 matoba", "2006 matoba et", "matoba et al. 2006", "al. 2006 babaie", "2006 babaie et", "babaie et al. 2007", "al. 2007 sun", "2007 sun et", "sun et al. 2008", "al. 2008 assou", "2008 assou et", "al. 2009 reviewed", "2009 reviewed in", "reviewed in kashyap et", "in kashyap et al.", "kashyap et al. 2009", "and zwaka 2012 .", "zwaka 2012 . in", "2012 . in vivo", "in vivo initiation", "vivo initiation of", "initiation of pluripotency may", "of pluripotency may depend", "pluripotency may depend on", "may depend on maternal", "depend on maternal factors", "on maternal factors transmitted", "maternal factors transmitted through", "factors transmitted through the", "transmitted through the oocyte", "the oocyte assou", "oocyte assou et", "al. 2009 and", "2009 and on", "and on dna demethylation", "on dna demethylation in", "dna demethylation in the", "demethylation in the zygote", "the zygote recently", "zygote recently reviewed", "recently reviewed in seisenberger", "reviewed in seisenberger et", "in seisenberger et al.", "seisenberger et al. 2013", "al. 2013 and", "2013 and hypoxia", "and hypoxia experienced by", "hypoxia experienced by the", "experienced by the blastocyst", "by the blastocyst in", "the blastocyst in the", "blastocyst in the reproductive", "in the reproductive tract", "the reproductive tract before", "reproductive tract before implantation", "before implantation forristal", "implantation forristal et", "forristal et al. 2010", "al. 2010 reviewed", "2010 reviewed in", "reviewed in mohyeldin et", "in mohyeldin et al.", "mohyeldin et al. 2010", "et al. 2010 .", "al. 2010 . in", "2010 . in vitro", "in vitro induced", "vitro induced pluripotency", "induced pluripotency may initiate", "pluripotency may initiate with", "may initiate with demethylation", "initiate with demethylation and", "with demethylation and activation", "demethylation and activation of", "and activation of the", "activation of the promoters", "of the promoters of", "the promoters of pou5f1", "of pou5f1 oct4", "oct4 and nanog", "and nanog bhutani", "nanog bhutani et", "bhutani et al. 2010", "al. 2010 . hypoxia", "2010 . hypoxia also", ". hypoxia also significantly", "hypoxia also significantly enhances", "also significantly enhances conversion", "significantly enhances conversion to", "enhances conversion to pluripotent", "conversion to pluripotent stem", "to pluripotent stem cells", "stem cells yoshida", "cells yoshida et", "yoshida et al. 2009", "et al. 2009 .", "al. 2009 . pou5f1", "2009 . pou5f1 and", ". pou5f1 and nanog", "and nanog together", "nanog together with", "with sox2 encode", "sox2 encode central", "encode central factors in", "central factors in pluripotency", "factors in pluripotency and", "in pluripotency and activate", "pluripotency and activate their", "and activate their own", "activate their own transcription", "own transcription boyer", "transcription boyer et", "boyer et al 2005", "al 2005 babaie", "2005 babaie et", "al. 2007 takahashi", "2007 takahashi et", "et al. 2007 .", "al. 2007 . the", "2007 . the autoactivation", ". the autoactivation loop", "the autoactivation loop maintains", "autoactivation loop maintains expression", "loop maintains expression of", "maintains expression of pou5f1", "of pou5f1 nanog", "nanog and sox2", "and sox2 at high", "sox2 at high levels", "at high levels in", "high levels in stem", "levels in stem cells", "in stem cells and", "cells and in", "and in turn", "in turn complexes", "turn complexes containing", "complexes containing various combinations", "containing various combinations of", "various combinations of these", "combinations of these factors", "these factors remenyi", "factors remenyi et", "remenyi et al. 2003", "al. 2003 lam", "2003 lam et", "lam et al. 2012", "al. 2012 activate", "2012 activate the", "activate the expression of", "the expression of a", "expression of a group", "of a group of", "a group of genes", "group of genes whose", "of genes whose products", "genes whose products are", "whose products are associated", "products are associated with", "are associated with rapid", "associated with rapid cell", "with rapid cell proliferation", "rapid cell proliferation and", "cell proliferation and repress", "proliferation and repress the", "and repress the expression", "repress the expression of", "are associated with cell", "associated with cell differentiation", "cell differentiation boyer", "differentiation boyer et", "al. 2005 matoba", "2005 matoba et", "al. 2007 chavez", "2007 chavez et", "chavez et al. 2009", "al. 2009 forristal", "2009 forristal et", "al. 2010 guenther", "2010 guenther 2011", "guenther 2011 .
              comparisons between", "2011 .
              comparisons between human", ".
              comparisons between human and", "between human and mouse", "human and mouse embryonic", "and mouse embryonic stem", "mouse embryonic stem cells", "embryonic stem cells must", "stem cells must be", "cells must be made", "must be made with", "be made with caution", "made with caution and", "with caution and for", "caution and for this", "and for this reason", "for this reason inferences", "this reason inferences from", "reason inferences from mouse", "inferences from mouse have", "from mouse have been", "mouse have been used", "have been used sparingly", "been used sparingly in", "used sparingly in this", "sparingly in this module.", "in this module. human", "this module. human escs", "module. human escs more", "human escs more closely", "escs more closely resemble", "more closely resemble mouse", "closely resemble mouse epiblast", "resemble mouse epiblast stem", "mouse epiblast stem cells", "epiblast stem cells in", "stem cells in having", "cells in having inactivated", "in having inactivated x", "having inactivated x chromosomes", "x chromosomes flattened", "chromosomes flattened morphology", "flattened morphology and", "morphology and intolerance", "and intolerance to passaging", "intolerance to passaging as", "to passaging as single", "passaging as single cells", "single cells hanna", "cells hanna et", "hanna et al. 2010", "al. 2010 . molecularly", ". molecularly human", "molecularly human escs", "human escs differ from", "escs differ from mouse", "differ from mouse escs", "from mouse escs in", "mouse escs in being", "escs in being maintained", "in being maintained by", "being maintained by fgf", "maintained by fgf and", "by fgf and activin/nodal/tgfbeta", "fgf and activin/nodal/tgfbeta signaling", "and activin/nodal/tgfbeta signaling rather", "activin/nodal/tgfbeta signaling rather than", "signaling rather than by", "rather than by lif", "than by lif and", "by lif and canonical", "lif and canonical wnt", "and canonical wnt signaling", "wnt signaling greber", "signaling greber et", "greber et al. 2010", "reviewed in katoh 2011", "in katoh 2011 .", "katoh 2011 . in", "2011 . in human", ". in human escs", "in human escs pou5f1", "human escs pou5f1 binds", "escs pou5f1 binds and", "pou5f1 binds and directly", "binds and directly activates", "and directly activates the", "directly activates the fgf2", "activates the fgf2 gene", "fgf2 gene however", "gene however pou5f1", "however pou5f1 does not", "pou5f1 does not activate", "does not activate fgf2", "not activate fgf2 in", "activate fgf2 in mouse", "fgf2 in mouse escs", "mouse escs reviewed", "escs reviewed in", "reviewed in de los", "in de los angeles", "de los angeles et", "los angeles et al.", "angeles et al. 2012", "al. 2012 . differences", "2012 . differences in", ". differences in expression", "differences in expression patterns", "in expression patterns of", "expression patterns of klf2", "of klf2 klf4", "lin28 nodal were", "nodal were observed between", "were observed between human", "observed between human and", "human and mouse escs", "mouse escs cai", "escs cai et", "cai et al. 2010", "al. 2010 as", "2010 as were", "as were differences in", "were differences in expression", "differences in expression of", "in expression of eomes", "of eomes arnt", "eomes arnt and", "arnt and several other", "and several other genes", "other genes ginis", "genes ginis et", "ginis et al.2004 .", "pluripotent stem cells are undifferentiated", "stem cells are undifferentiated cells", "cells are undifferentiated cells posessing", "are undifferentiated cells posessing an", "undifferentiated cells posessing an abbreviated", "cells posessing an abbreviated cell", "posessing an abbreviated cell cycle", "abbreviated cell cycle reviewed", "cell cycle reviewed in", "cycle reviewed in stein", "reviewed in stein et al.", "in stein et al. 2012", "al. 2012 a", "2012 a characteristic", "a characteristic profile of gene", "characteristic profile of gene expression", "of gene expression rao", "gene expression rao et", "expression rao et al.", "et al. 2004 kim", "al. 2004 kim et", "2004 kim et al.", "et al. 2006 player", "al. 2006 player et", "2006 player et al.", "et al. 2006 wang", "al. 2006 wang et", "2006 wang et al", "wang et al 2006 using", "et al 2006 using mouse", "2006 using mouse international", "using mouse international stem", "mouse international stem cell", "international stem cell initiative 2007", "cell initiative 2007 assou", "initiative 2007 assou et", "2007 assou et al.", "et al. 2007 assou", "al. 2007 assou et", "et al. 2009 ding", "al. 2009 ding et", "2009 ding et al.", "ding et al. 2012 using", "et al. 2012 using mouse", "using mouse and", "mouse and the", "and the ability to self", "the ability to self renew", "ability to self renew and", "to self renew and generate", "self renew and generate all", "renew and generate all cell", "and generate all cell types", "generate all cell types of", "all cell types of the", "cell types of the body", "types of the body except", "of the body except extraembryonic", "the body except extraembryonic lineages", "except extraembryonic lineages marti", "extraembryonic lineages marti et", "lineages marti et al.", "et al. 2013 reviewed", "al. 2013 reviewed in", "2013 reviewed in romeo", "reviewed in romeo et al.", "in romeo et al. 2012", "romeo et al. 2012 .", "et al. 2012 . they", "al. 2012 . they are", "2012 . they are a", ". they are a major", "they are a major cell", "are a major cell type", "a major cell type in", "major cell type in the", "cell type in the inner", "type in the inner cell", "in the inner cell mass", "the inner cell mass of", "inner cell mass of the", "cell mass of the early", "mass of the early embryo", "of the early embryo in", "the early embryo in vivo", "embryo in vivo and", "in vivo and cells", "vivo and cells with", "and cells with the same", "cells with the same properties", "the same properties induced", "same properties induced pluripotent", "properties induced pluripotent stem", "pluripotent stem cells can", "stem cells can be", "cells can be generated", "can be generated in vitro", "be generated in vitro from", "generated in vitro from differentiated", "in vitro from differentiated adult", "vitro from differentiated adult cells", "from differentiated adult cells by", "differentiated adult cells by overexpression", "adult cells by overexpression of", "cells by overexpression of a", "by overexpression of a set", "overexpression of a set of", "of a set of transcription", "a set of transcription factor", "set of transcription factor genes", "transcription factor genes takahashi", "factor genes takahashi and", "genes takahashi and yamanaka", "and yamanaka 2006 takahashi", "yamanaka 2006 takahashi et", "2006 takahashi et al.", "et al. 2007 yu", "al. 2007 yu et", "2007 yu et al.", "et al. 2007 jaenisch", "al. 2007 jaenisch and", "2007 jaenisch and young", "and young 2008 stein", "young 2008 stein et", "2008 stein et al.", "et al. 2012 reviewed", "al. 2012 reviewed in", "2012 reviewed in dejosez", "reviewed in dejosez and zwaka", "in dejosez and zwaka 2012", "dejosez and zwaka 2012 .
              pluripotency", "and zwaka 2012 .
              pluripotency is", "zwaka 2012 .
              pluripotency is maintained", "2012 .
              pluripotency is maintained by", ".
              pluripotency is maintained by a", "is maintained by a self", "maintained by a self reinforcing", "by a self reinforcing loop", "a self reinforcing loop of", "self reinforcing loop of transcription", "reinforcing loop of transcription factors", "of transcription factors boyer", "transcription factors boyer et", "factors boyer et al.", "et al. 2005 rao", "al. 2005 rao et", "2005 rao et al.", "et al. 2006 matoba", "al. 2006 matoba et", "2006 matoba et al.", "et al. 2006 babaie", "al. 2006 babaie et", "2006 babaie et al.", "et al. 2007 sun", "al. 2007 sun et", "2007 sun et al.", "et al. 2008 assou", "al. 2008 assou et", "2008 assou et al.", "et al. 2009 reviewed", "al. 2009 reviewed in", "2009 reviewed in kashyap", "reviewed in kashyap et al.", "in kashyap et al. 2009", "2009 reviewed in dejosez", "dejosez and zwaka 2012 .", "and zwaka 2012 . in", "zwaka 2012 . in vivo", ". in vivo initiation", "in vivo initiation of", "vivo initiation of pluripotency", "initiation of pluripotency may depend", "of pluripotency may depend on", "pluripotency may depend on maternal", "may depend on maternal factors", "depend on maternal factors transmitted", "on maternal factors transmitted through", "maternal factors transmitted through the", "factors transmitted through the oocyte", "through the oocyte assou", "the oocyte assou et", "oocyte assou et al.", "et al. 2009 and", "al. 2009 and on", "2009 and on dna", "and on dna demethylation in", "on dna demethylation in the", "dna demethylation in the zygote", "in the zygote recently", "the zygote recently reviewed", "zygote recently reviewed in", "recently reviewed in seisenberger et", "reviewed in seisenberger et al.", "in seisenberger et al. 2013", "et al. 2013 and", "al. 2013 and hypoxia", "2013 and hypoxia experienced", "and hypoxia experienced by the", "hypoxia experienced by the blastocyst", "experienced by the blastocyst in", "by the blastocyst in the", "the blastocyst in the reproductive", "blastocyst in the reproductive tract", "in the reproductive tract before", "the reproductive tract before implantation", "tract before implantation forristal", "before implantation forristal et", "implantation forristal et al.", "et al. 2010 reviewed", "al. 2010 reviewed in", "2010 reviewed in mohyeldin", "reviewed in mohyeldin et al.", "in mohyeldin et al. 2010", "mohyeldin et al. 2010 .", "et al. 2010 . in", "al. 2010 . in vitro", ". in vitro induced", "in vitro induced pluripotency", "vitro induced pluripotency may", "induced pluripotency may initiate with", "pluripotency may initiate with demethylation", "may initiate with demethylation and", "initiate with demethylation and activation", "with demethylation and activation of", "demethylation and activation of the", "and activation of the promoters", "activation of the promoters of", "of the promoters of pou5f1", "promoters of pou5f1 oct4", "pou5f1 oct4 and", "and nanog bhutani et", "nanog bhutani et al.", "bhutani et al. 2010 .", "et al. 2010 . hypoxia", "al. 2010 . hypoxia also", "2010 . hypoxia also significantly", ". hypoxia also significantly enhances", "hypoxia also significantly enhances conversion", "also significantly enhances conversion to", "significantly enhances conversion to pluripotent", "enhances conversion to pluripotent stem", "conversion to pluripotent stem cells", "pluripotent stem cells yoshida", "stem cells yoshida et", "cells yoshida et al.", "yoshida et al. 2009 .", "et al. 2009 . pou5f1", "al. 2009 . pou5f1 and", "2009 . pou5f1 and nanog", "pou5f1 and nanog together", "and nanog together with", "nanog together with sox2", "together with sox2 encode", "with sox2 encode central", "sox2 encode central factors", "encode central factors in pluripotency", "central factors in pluripotency and", "factors in pluripotency and activate", "in pluripotency and activate their", "pluripotency and activate their own", "and activate their own transcription", "their own transcription boyer", "own transcription boyer et", "transcription boyer et al", "et al 2005 babaie", "al 2005 babaie et", "2005 babaie et al.", "et al. 2007 takahashi", "al. 2007 takahashi et", "2007 takahashi et al.", "takahashi et al. 2007 .", "et al. 2007 . the", "al. 2007 . the autoactivation", "2007 . the autoactivation loop", ". the autoactivation loop maintains", "the autoactivation loop maintains expression", "autoactivation loop maintains expression of", "loop maintains expression of pou5f1", "expression of pou5f1 nanog", "pou5f1 nanog and", "nanog and sox2 at", "and sox2 at high levels", "sox2 at high levels in", "at high levels in stem", "high levels in stem cells", "levels in stem cells and", "stem cells and in", "cells and in turn", "in turn complexes containing", "turn complexes containing various", "complexes containing various combinations of", "containing various combinations of these", "various combinations of these factors", "of these factors remenyi", "these factors remenyi et", "factors remenyi et al.", "et al. 2003 lam", "al. 2003 lam et", "2003 lam et al.", "et al. 2012 activate", "al. 2012 activate the", "2012 activate the expression", "activate the expression of a", "the expression of a group", "expression of a group of", "of a group of genes", "a group of genes whose", "group of genes whose products", "of genes whose products are", "genes whose products are associated", "whose products are associated with", "products are associated with rapid", "are associated with rapid cell", "associated with rapid cell proliferation", "with rapid cell proliferation and", "rapid cell proliferation and repress", "cell proliferation and repress the", "proliferation and repress the expression", "and repress the expression of", "repress the expression of a", "products are associated with cell", "are associated with cell differentiation", "with cell differentiation boyer", "cell differentiation boyer et", "differentiation boyer et al.", "et al. 2005 matoba", "al. 2005 matoba et", "2005 matoba et al.", "et al. 2007 chavez", "al. 2007 chavez et", "2007 chavez et al.", "et al. 2009 forristal", "al. 2009 forristal et", "2009 forristal et al.", "et al. 2010 guenther", "al. 2010 guenther 2011", "2010 guenther 2011 .
              comparisons", "guenther 2011 .
              comparisons between human", "2011 .
              comparisons between human and", ".
              comparisons between human and mouse", "between human and mouse embryonic", "human and mouse embryonic stem", "and mouse embryonic stem cells", "mouse embryonic stem cells must", "embryonic stem cells must be", "stem cells must be made", "cells must be made with", "must be made with caution", "be made with caution and", "made with caution and for", "with caution and for this", "caution and for this reason", "and for this reason inferences", "for this reason inferences from", "this reason inferences from mouse", "reason inferences from mouse have", "inferences from mouse have been", "from mouse have been used", "mouse have been used sparingly", "have been used sparingly in", "been used sparingly in this", "used sparingly in this module.", "sparingly in this module. human", "in this module. human escs", "this module. human escs more", "module. human escs more closely", "human escs more closely resemble", "escs more closely resemble mouse", "more closely resemble mouse epiblast", "closely resemble mouse epiblast stem", "resemble mouse epiblast stem cells", "mouse epiblast stem cells in", "epiblast stem cells in having", "stem cells in having inactivated", "cells in having inactivated x", "in having inactivated x chromosomes", "inactivated x chromosomes flattened", "x chromosomes flattened morphology", "flattened morphology and intolerance", "morphology and intolerance to", "and intolerance to passaging as", "intolerance to passaging as single", "to passaging as single cells", "as single cells hanna", "single cells hanna et", "cells hanna et al.", "hanna et al. 2010 .", "et al. 2010 . molecularly", "2010 . molecularly human", ". molecularly human escs", "molecularly human escs differ", "human escs differ from mouse", "escs differ from mouse escs", "differ from mouse escs in", "from mouse escs in being", "mouse escs in being maintained", "escs in being maintained by", "in being maintained by fgf", "being maintained by fgf and", "maintained by fgf and activin/nodal/tgfbeta", "by fgf and activin/nodal/tgfbeta signaling", "fgf and activin/nodal/tgfbeta signaling rather", "and activin/nodal/tgfbeta signaling rather than", "activin/nodal/tgfbeta signaling rather than by", "signaling rather than by lif", "rather than by lif and", "than by lif and canonical", "by lif and canonical wnt", "lif and canonical wnt signaling", "canonical wnt signaling greber", "wnt signaling greber et", "signaling greber et al.", "2010 reviewed in katoh", "reviewed in katoh 2011 .", "in katoh 2011 . in", "katoh 2011 . in human", "2011 . in human escs", ". in human escs pou5f1", "in human escs pou5f1 binds", "human escs pou5f1 binds and", "escs pou5f1 binds and directly", "pou5f1 binds and directly activates", "binds and directly activates the", "and directly activates the fgf2", "directly activates the fgf2 gene", "the fgf2 gene however", "fgf2 gene however pou5f1", "gene however pou5f1 does", "however pou5f1 does not activate", "pou5f1 does not activate fgf2", "does not activate fgf2 in", "not activate fgf2 in mouse", "activate fgf2 in mouse escs", "in mouse escs reviewed", "mouse escs reviewed in", "escs reviewed in de", "reviewed in de los angeles", "in de los angeles et", "de los angeles et al.", "los angeles et al. 2012", "angeles et al. 2012 .", "et al. 2012 . differences", "al. 2012 . differences in", "2012 . differences in expression", ". differences in expression patterns", "differences in expression patterns of", "in expression patterns of klf2", "patterns of klf2 klf4", "klf2 klf4 klf5", "klf4 klf5 esrrb", "klf5 esrrb foxd3", "esrrb foxd3 socs3", "foxd3 socs3 lin28", "socs3 lin28 nodal", "lin28 nodal were observed", "nodal were observed between human", "were observed between human and", "observed between human and mouse", "between human and mouse escs", "and mouse escs cai", "mouse escs cai et", "escs cai et al.", "et al. 2010 as", "al. 2010 as were", "2010 as were differences", "as were differences in expression", "were differences in expression of", "differences in expression of eomes", "expression of eomes arnt", "of eomes arnt and", "eomes arnt and several", "arnt and several other genes", "several other genes ginis", "other genes ginis et", "genes ginis et al.2004" ] }, { "record_id": "GLY_000594_1_991", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4641263", "r hsa", "hsa 4641263", "r hsa 4641263" ] }, { "record_id": "GLY_000594_1_991", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of fzd", "fzd by", "by ubiquitination", "regulation of fzd", "of fzd by", "fzd by ubiquitination", "regulation of fzd by", "of fzd by ubiquitination", "regulation of fzd by ubiquitination", "wnt responsiveness", "responsiveness is", "is influenced", "influenced by", "by expression", "expression levels", "levels of", "fzd and", "and lrp", "lrp proteins.", "of these", "these receptors", "receptors at", "at the", "the cell", "cell surface", "surface are", "are regulated", "regulated in", "in part", "part by", "by endocytosis", "but the", "the mechanisms", "mechanisms are", "are not", "not fully", "fully elucidated", "garliardi et", "et al", "2008 .", "a number", "number of", "of recent", "recent studies", "studies have", "have identified", "identified a", "a role", "role for", "for ubiquitination", "ubiquitination in", "in the", "the localization", "localization and", "and turnover", "turnover of", "of wnt", "wnt receptors", "the plasma", "plasma membrane.", "znrf3 and", "and rnf43", "rnf43 are", "are e3", "e3 ligases", "ligases that", "that have", "have been", "been shown", "shown to", "to ubiquitinate", "ubiquitinate fzd", "fzd proteins", "proteins and", "and promote", "promote their", "their lysosomal", "lysosomal degradation", "while the", "the deubiquitinating", "deubiquitinating enzyme", "enzyme usp8", "usp8 promotes", "promotes recycling", "recycling of", "of the", "the receptor", 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cell surface", "cell surface are", "surface are regulated", "are regulated in", "regulated in part", "in part by", "part by endocytosis", "endocytosis but", "but the mechanisms", "the mechanisms are", "mechanisms are not", "are not fully", "not fully elucidated", "elucidated garliardi", "garliardi et al", "al 2008", ". a", "a number of", "number of recent", "of recent studies", "recent studies have", "studies have identified", "have identified a", "identified a role", "a role for", "role for ubiquitination", "for ubiquitination in", "ubiquitination in the", "in the localization", "the localization and", "localization and turnover", "and turnover of", "turnover of wnt", "of wnt receptors", "wnt receptors at", "at the plasma", "the plasma membrane.", "membrane. znrf3", "znrf3 and rnf43", "and rnf43 are", "rnf43 are e3", "are e3 ligases", "e3 ligases that", "ligases that have", "that have been", "have been shown", "been shown to", "shown to ubiquitinate", "to ubiquitinate fzd", 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              four", ".

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              four", "2009 .

              four biosynthetic", ".

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              four", "al. 2009 .

              four biosynthetic", "2009 .

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              four", "et al. 2009 .

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matter", "retardation white matter changes", "white matter changes and structural", "matter changes and structural brain", "changes and structural brain abnormalities", "structural brain abnormalities longman", "brain abnormalities longman et", "abnormalities longman et al.", "longman et al. 2003 ." ] }, { "record_id": "GLY_000594_1_998", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5140745", "r hsa", "hsa 5140745", "r hsa 5140745" ] }, { "record_id": "GLY_000594_1_998", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "wnt5a dependent", "dependent internalization", "internalization of", "of fzd2", "fzd5 and", "and ror2", "wnt5a dependent internalization", "dependent internalization of", "internalization of fzd2", "fzd2 fzd5", "fzd5 and ror2", "wnt5a dependent internalization of", "dependent internalization of fzd2", "of fzd2 fzd5", "fzd2 fzd5 and", "wnt5a dependent internalization of fzd2", 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"fieldtype": "text", "phraselist": [ "o linked", "linked glycosylation", "o linked glycosylation", "o glycosylation", "glycosylation is", "is an", "an important", "important post", "post translational", "translational modification", "required for", "for correct", "correct functioning", "functioning of", "of many", "many proteins", "van den", "den steen", "steen et", "et al.", "al. 1998", "moremen et", "al. 2012", "2012 .", "o glycosylation is", "glycosylation is an", "is an important", "an important post", "important post translational", "post translational modification", "modification ptm", "ptm required", "required for correct", "for correct functioning", "correct functioning of", "functioning of many", "of many proteins", "proteins van", "van den steen", "den steen et", "steen et al.", "et al. 1998", "1998 moremen", "moremen et al.", "et al. 2012", "al. 2012 .", "o glycosylation is an", "glycosylation is an important", "is an important post", "an important post translational", "important post translational modification", "translational modification ptm", "ptm required for", "required for correct functioning", "for correct functioning of", "correct functioning of many", "functioning of many proteins", "many proteins van", "proteins van den", "van den steen et", "den steen et al.", "steen et al. 1998", "al. 1998 moremen", "1998 moremen et", "moremen et al. 2012", "et al. 2012 .", "o glycosylation is an important", "glycosylation is an important post", "is an important post translational", "an important post translational modification", "post translational modification ptm", "modification ptm required", "ptm required for correct", "required for correct functioning of", "for correct functioning of many", "correct functioning of many proteins", "of many proteins van", "many proteins van den", "proteins van den steen", "van den steen et al.", "den steen et al. 1998", "et al. 1998 moremen", "al. 1998 moremen et", "1998 moremen et al.", "moremen et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1000", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5205685", "r hsa", "hsa 5205685", "r hsa 5205685" ] }, { "record_id": "GLY_000594_1_1000", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pink1 prkn", "prkn mediated", "mediated mitophagy", "pink1 prkn mediated", "prkn mediated mitophagy", "pink1 prkn mediated mitophagy", "this is", "is the", "the process", "process of", "of selective", "selective removal", "removal of", "of damaged", "damaged mitochondria", "mitochondria by", "by autophagosomes", "autophagosomes and", "and subsequent", "subsequent catabolism", "catabolism by", "by lysosomes.", "lysosomes. in", "in healthy", "healthy mitochondria", "mitochondria pten", "pten induced", "induced putative", "putative kinase", "kinase 1", "is imported", "imported to", "to the", "the inner", "inner mitochondrial", "mitochondrial membrane", "presumably through", "through the", "the tom/tim", "tom/tim complex.", "complex. the", "the tim", "tim complex", "complex associated", "associated protease", "mitochondrial mpp", "cleaves pink1", "pink1 mitochondrial", "mitochondrial targeting", "targeting sequence", "mts .", ". pink1", "pink1 may", "may be", "be cleaved", "cleaved by", "by the", "inner membrane", "membrane presenilin", "presenilin associated", "associated rhomboid", "rhomboid like", "like protease", "and ultimately", "ultimately proteolytically", "proteolytically degraded.", "degraded. loss", "loss of", "of membrane", "membrane potential", "potential in", "in damaged", "mitochondria prevents", "prevents the", "the import", "import of", "of pink1", "pink1 which", "which accumulates", "accumulates on\u00a0the", "on\u00a0the mitochondrial\u00a0outer", "mitochondrial\u00a0outer membrane", "of the", "the defective", "defective mitochondria.", "mitochondria. activation", "activation of", "pink1 at", "at mom\u00a0is", "mom\u00a0is achieved", "achieved via\u00a0dimerization", "via\u00a0dimerization mediated", "mediated trans", "trans autophosphorylation", "autophosphorylation of", "at multiple", "multiple sites", "sites including", "including s228", "s228 and", "and s402", "okatsu\u00a0k et", "et al.", "2013 aerts", "aerts l", "l et", "2015 rasool", "rasool s", "s et", "gan zy", "zy et", "2022 .", ". activated", "activated pink1", "pink1 phosphorylates", "phosphorylates s65", "s65 of", "of ubiquitin", "on mom", "mom proteins", "proteins which", "which leads", "leads to", "to increased", "increased recruitment", "recruitment of", "the e3", "e3 ubiquitin", "ubiquitin ligase", "ligase parkin", "to damaged", "koyano f", "f et", "shiba fukushima", "fukushima k", "k et", "ordureau\u00a0a et\u00a0al.", "2015 .", "pink1 also", "also phosphorylates", "phosphorylates prkn", "prkn at", "at s65", "s65 in", "in the", "the n", "n terminal", "terminal ub", "ub like", "like domain", "domain inducing", "inducing the", "e3 ligase", "ligase activity", "activity of", "of prkn", "kondapalli et", "kazlauskaite a", "a et", "activated prkn", "prkn promotes", "promotes the", "the ubiquitination", "ubiquitination of", "of mitochondrial", "mitochondrial substrates", "substrates including", "including mitofusin", "mitofusin 1", "1 and", "and 2", "and the", "the voltage", "voltage dependent", "dependent anion", "anion channel", "channel 1", "and 3", "3 .", ". the", "prkn generates", "generates ub", "ub moieties", "moieties for", "for pink1", "pink1 mediated", "mediated phosphorylation", "phosphorylation of", "of ub", "ub thus", "thus leading", "leading to", "to a", "a feedforward", "feedforward loop", "loop in", "the pink1:prkn", "pink1:prkn pathway", "sauve v", "v et", ". ubiquitin", "ubiquitin chains", "chains on", "on prkn", "prkn ubiquitinated", "ubiquitinated substrates", "substrates recruit", "recruit cargo", "cargo receptors", "receptors such", "such as", "as sqstm1", "and optn", "optn linking", "linking the", "the ubiquitinated", "substrates to", "the microtubule", "microtubule associated", "associated proteins", "proteins 1a/1b", "1a/1b light", "light chain", "chain 3", "heo lm", "lm et", "lazarou m", "m et", "the recruitment", "of both", "both map1lc3", "complexes and", "the autophagy", "autophagy proteins", "proteins 5", "5 and", "and 12", "atg5: atg12", "complex to", "the autophagosome", "autophagosome membrane", "membrane promotes", "promotes autophagosome", "autophagosome formation.", "formation. the", "the mitochondrion", "mitochondrion is", "is engulfed", "engulfed after", "after the", "the isolation", "isolation membrane", "membrane grows", "grows to", "a sufficient", "sufficient size", "size to", "to engulf", "engulf the", "the mitochondrion.", "mitochondrion. once", "once autophagic", "autophagic vesicle", "vesicle formation", "formation is", "is complete", "vesicle fusion", "fusion with", "with lysosomes", "lysosomes occurs", "occurs to", "to form", "form autophagolysosomes", "autophagolysosomes in", "in which", "which the", "the lysosomal", "lysosomal hydrolases", "cathepsins and", "and lipases", "degrade the", "the intra", "intra autophagosomal", "autophagosomal content.", "content. cathepsin", "cathepsin also", "also degrades", "degrades lc3", "lc3 on", "on the", "autophagosomal surface", "surface of", "the autophagic", "autophagic vesicle.", "this is the", "is the process", "the process of", "process of selective", "of selective removal", "selective removal of", "removal of damaged", "of damaged mitochondria", "damaged mitochondria by", "mitochondria by autophagosomes", "by autophagosomes and", "autophagosomes and subsequent", "and subsequent catabolism", "subsequent catabolism by", "catabolism by lysosomes.", "by lysosomes. in", "lysosomes. in healthy", "in healthy mitochondria", "healthy mitochondria pten", "mitochondria pten induced", "pten induced putative", "induced putative kinase", "putative kinase 1", "1 pink1", "pink1 is", "is imported to", "imported to the", "to the inner", "the inner mitochondrial", "inner mitochondrial membrane", "membrane presumably", "presumably through the", "through the tom/tim", "the tom/tim complex.", "tom/tim complex. the", "complex. the tim", "the tim complex", "tim complex associated", "complex associated protease", "protease mitochondrial", "mpp cleaves", "cleaves pink1 mitochondrial", "pink1 mitochondrial targeting", "mitochondrial targeting sequence", "sequence mts", "mts . pink1", ". pink1 may", "pink1 may be", "may be cleaved", "be cleaved by", "cleaved by the", "by the inner", "the inner membrane", "inner membrane presenilin", "membrane presenilin associated", "presenilin associated rhomboid", "associated rhomboid like", "rhomboid like protease", "protease parl", "parl and", "and ultimately proteolytically", "ultimately proteolytically degraded.", "proteolytically degraded. loss", "degraded. loss of", "loss of membrane", "of membrane potential", "membrane potential in", "potential in damaged", "in damaged mitochondria", "damaged mitochondria prevents", "mitochondria prevents the", "prevents the import", "the import of", "import of pink1", "of pink1 which", "pink1 which accumulates", "which accumulates on\u00a0the", "accumulates on\u00a0the mitochondrial\u00a0outer", "on\u00a0the mitochondrial\u00a0outer membrane", "membrane mom", "mom of", "of the defective", "the defective mitochondria.", "defective mitochondria. activation", "mitochondria. activation of", "activation of pink1", "of pink1 at", "pink1 at mom\u00a0is", "at mom\u00a0is achieved", "mom\u00a0is achieved via\u00a0dimerization", "achieved via\u00a0dimerization mediated", "via\u00a0dimerization mediated trans", "mediated trans autophosphorylation", "trans autophosphorylation of", "autophosphorylation of pink1", "pink1 at multiple", "at multiple sites", "multiple sites including", "sites including s228", "including s228 and", "s228 and s402", "s402 okatsu\u00a0k", "okatsu\u00a0k et al.", "al. 2012", "2012 2013", "2013 aerts l", "aerts l et", "l et al.", "al. 2015", "2015 rasool s", "rasool s et", "s et al.", "al. 2018", "2018 2022", "2022 gan", "gan zy et", "zy et al.", "al. 2022", "2022 . activated", ". activated pink1", "activated pink1 phosphorylates", "pink1 phosphorylates s65", "phosphorylates s65 of", "s65 of ubiquitin", "ubiquitin ub", "ub on", "on mom proteins", "mom proteins which", "proteins which leads", "which leads to", "leads to increased", "to increased recruitment", "increased recruitment of", "recruitment of the", "of the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase parkin", "parkin prkn", "prkn to", "to damaged mitochondria", "mitochondria koyano", "koyano f et", "f et al.", "al. 2014", "2014 shiba", "shiba fukushima k", "fukushima k et", "k et al.", "2014 ordureau\u00a0a", "et\u00a0al. 2015", "2015 . activated", "activated pink1 also", "pink1 also phosphorylates", "also phosphorylates prkn", "phosphorylates prkn at", "prkn at s65", "at s65 in", "s65 in the", "in the n", "the n terminal", "n terminal ub", "terminal ub like", "ub like domain", "like domain inducing", "domain inducing the", "inducing the e3", "the e3 ligase", "e3 ligase activity", "ligase activity of", "activity of prkn", "prkn kondapalli", "kondapalli et al.", "2012 kazlauskaite", "kazlauskaite a et", "a et al.", "2015 ordureau\u00a0a", ". activated prkn", "activated prkn promotes", "prkn promotes the", "promotes the ubiquitination", "the ubiquitination of", "ubiquitination of mitochondrial", "of mitochondrial substrates", "mitochondrial substrates including", "substrates including mitofusin", "including mitofusin 1", "mitofusin 1 and", "1 and 2", "2 mfn1", "mfn1 2", "2 and", "and the voltage", "the voltage dependent", "voltage dependent anion", "dependent anion channel", "anion channel 1", "channel 1 and", "1 and 3", "3 vdac1", "vdac1 3", "3 . the", ". the e3", "of prkn generates", "prkn generates ub", "generates ub moieties", "ub moieties for", "moieties for pink1", "for pink1 mediated", "pink1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of ub", "of ub thus", "ub thus leading", "thus leading to", "leading to a", "to a feedforward", "a feedforward loop", "feedforward loop in", "loop in the", "in the pink1:prkn", "the pink1:prkn pathway", "pathway ordureau\u00a0a", "2015 sauve", "sauve v et", "v et al.", "2022 . ubiquitin", ". ubiquitin chains", "ubiquitin chains on", "chains on prkn", "on prkn ubiquitinated", "prkn ubiquitinated substrates", "ubiquitinated substrates recruit", "substrates recruit cargo", "recruit cargo receptors", "cargo receptors such", "receptors such as", "such as sqstm1", "sqstm1 p62", "p62 and", "and optn linking", "optn linking the", "linking the ubiquitinated", "the ubiquitinated substrates", "ubiquitinated substrates to", "substrates to the", "to the microtubule", "the microtubule associated", "microtubule associated proteins", "associated proteins 1a/1b", "proteins 1a/1b light", "1a/1b light chain", "light chain 3", "3 lc3", "lc3 map1lc3", "heo lm et", "lm et al.", "2015 lazarou", "lazarou m et", "m et al.", "2015 . the", ". the recruitment", "the recruitment of", "recruitment of both", "of both map1lc3", "map1lc3 lc3", "lc3 complexes", "complexes and the", "and the autophagy", "the autophagy proteins", "autophagy proteins 5", "proteins 5 and", "5 and 12", "12 atg5:", "atg12 complex", "complex to the", "to the autophagosome", "the autophagosome membrane", "autophagosome membrane promotes", "membrane promotes autophagosome", "promotes autophagosome formation.", "autophagosome formation. the", "formation. the mitochondrion", "the mitochondrion is", "mitochondrion is engulfed", "is engulfed after", "engulfed after the", "after the isolation", "the isolation membrane", "isolation membrane grows", "membrane grows to", "grows to a", "to a sufficient", "a sufficient size", "sufficient size to", "size to engulf", "to engulf the", "engulf the mitochondrion.", "the mitochondrion. once", "mitochondrion. once autophagic", "once autophagic vesicle", "autophagic vesicle formation", "vesicle formation is", "formation is complete", "complete vesicle", "vesicle fusion with", "fusion with lysosomes", "with lysosomes occurs", "lysosomes occurs to", "occurs to form", "to form autophagolysosomes", "form autophagolysosomes in", "autophagolysosomes in which", "in which the", "which the lysosomal", "the lysosomal hydrolases", "hydrolases cathepsins", "cathepsins and lipases", "lipases degrade", "degrade the intra", "the intra autophagosomal", "intra autophagosomal content.", "autophagosomal content. cathepsin", "content. cathepsin also", "cathepsin also degrades", "also degrades lc3", "degrades lc3 on", "lc3 on the", "on the intra", "intra autophagosomal surface", "autophagosomal surface of", "surface of the", "of the autophagic", "the autophagic vesicle.", "this is the process", "is the process of", "the process of selective", "process of selective removal", "of selective removal of", "selective removal of damaged", "removal of damaged mitochondria", "of damaged mitochondria by", "damaged mitochondria by autophagosomes", "mitochondria by autophagosomes and", "by autophagosomes and subsequent", "autophagosomes and subsequent catabolism", "and subsequent catabolism by", "subsequent catabolism by lysosomes.", "catabolism by lysosomes. in", "by lysosomes. in healthy", "lysosomes. in healthy mitochondria", "in healthy mitochondria pten", "healthy mitochondria pten induced", "mitochondria pten induced putative", "pten induced putative kinase", "induced putative kinase 1", "kinase 1 pink1", "pink1 is imported", "is imported to the", "imported to the inner", "to the inner mitochondrial", "the inner mitochondrial membrane", "mitochondrial membrane presumably", "membrane presumably through", "presumably through the tom/tim", "through the tom/tim complex.", "the tom/tim complex. the", "tom/tim complex. the tim", "complex. the tim complex", "the tim complex associated", "tim complex associated protease", "associated protease mitochondrial", "protease mitochondrial mpp", "mitochondrial mpp cleaves", "mpp cleaves pink1", "cleaves pink1 mitochondrial targeting", "pink1 mitochondrial targeting sequence", "targeting sequence mts", "sequence mts .", "mts . pink1 may", ". pink1 may be", "pink1 may be cleaved", "may be cleaved by", "be cleaved by the", "cleaved by the inner", "by the inner membrane", "the inner membrane presenilin", "inner membrane presenilin associated", "membrane presenilin associated rhomboid", "presenilin associated rhomboid like", "associated rhomboid like protease", "like protease parl", "parl and ultimately", "and ultimately proteolytically degraded.", "ultimately proteolytically degraded. loss", "proteolytically degraded. loss of", "degraded. loss of membrane", "loss of membrane potential", "of membrane potential in", "membrane potential in damaged", "potential in damaged mitochondria", "in damaged mitochondria prevents", "damaged mitochondria prevents the", "mitochondria prevents the import", "prevents the import of", "the import of pink1", "import of pink1 which", "of pink1 which accumulates", "pink1 which accumulates on\u00a0the", "which accumulates on\u00a0the mitochondrial\u00a0outer", "accumulates on\u00a0the mitochondrial\u00a0outer membrane", "mitochondrial\u00a0outer membrane mom", "mom of the", "of the defective mitochondria.", "the defective mitochondria. activation", "defective mitochondria. activation of", "mitochondria. activation of pink1", "activation of pink1 at", "of pink1 at mom\u00a0is", "pink1 at mom\u00a0is achieved", "at mom\u00a0is achieved via\u00a0dimerization", "mom\u00a0is achieved via\u00a0dimerization mediated", "achieved via\u00a0dimerization mediated trans", "via\u00a0dimerization mediated trans autophosphorylation", "mediated trans autophosphorylation of", "trans autophosphorylation of pink1", "autophosphorylation of pink1 at", "of pink1 at multiple", "pink1 at multiple sites", "at multiple sites including", "multiple sites including s228", "sites including s228 and", "including s228 and s402", "and s402 okatsu\u00a0k", "s402 okatsu\u00a0k et", "et al. 2012", "2012 2013 aerts", "2013 aerts l et", "aerts l et al.", "et al. 2015", "al. 2015 rasool", "2015 rasool s et", "rasool s et al.", "et al. 2018", "2022 gan zy", "gan zy et al.", "et al. 2022", "al. 2022 .", "2022 . activated pink1", ". activated pink1 phosphorylates", "activated pink1 phosphorylates s65", "pink1 phosphorylates s65 of", "phosphorylates s65 of ubiquitin", "of ubiquitin ub", "ub on mom", "on mom proteins which", "mom proteins which leads", "proteins which leads to", "which leads to increased", "leads to increased recruitment", "to increased recruitment of", "increased recruitment of the", "recruitment of the e3", "of the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase parkin", "ligase parkin prkn", "prkn to damaged", "damaged mitochondria koyano", "mitochondria koyano f", "koyano f et al.", "et al. 2014", "2014 shiba fukushima", "shiba fukushima k et", "fukushima k et al.", "2014 ordureau\u00a0a et\u00a0al.", "ordureau\u00a0a et\u00a0al. 2015", "et\u00a0al. 2015 .", "2015 . activated pink1", ". activated pink1 also", "activated pink1 also phosphorylates", "pink1 also phosphorylates prkn", "also phosphorylates prkn at", "phosphorylates prkn at s65", "prkn at s65 in", "at s65 in the", "s65 in the n", "in the n terminal", "the n terminal ub", "n terminal ub like", "terminal ub like domain", "ub like domain inducing", "like domain inducing the", "domain inducing the e3", "inducing the e3 ligase", "the e3 ligase activity", "e3 ligase activity of", "ligase activity of prkn", "of prkn kondapalli", "prkn kondapalli et", "2012 kazlauskaite a", "kazlauskaite a et al.", "2015 ordureau\u00a0a et\u00a0al.", "2015 . activated prkn", ". activated prkn promotes", "activated prkn promotes the", "prkn promotes the ubiquitination", "promotes the ubiquitination of", "the ubiquitination of mitochondrial", "ubiquitination of mitochondrial substrates", "of mitochondrial substrates including", "mitochondrial substrates including mitofusin", "substrates including mitofusin 1", "including mitofusin 1 and", "mitofusin 1 and 2", "and 2 mfn1", "2 and the", "and the voltage dependent", "the voltage dependent anion", "voltage dependent anion channel", "dependent anion channel 1", "anion channel 1 and", "channel 1 and 3", "and 3 vdac1", "vdac1 3 .", "3 . the e3", ". the e3 ligase", "activity of prkn generates", "of prkn generates ub", "prkn generates ub moieties", "generates ub moieties for", "ub moieties for pink1", "moieties for pink1 mediated", "for pink1 mediated phosphorylation", "pink1 mediated phosphorylation of", "mediated phosphorylation of ub", "phosphorylation of ub thus", "of ub thus leading", "ub thus leading to", "thus leading to a", "leading to a feedforward", "to a feedforward loop", "a feedforward loop in", "feedforward loop in the", "loop in the pink1:prkn", "in the pink1:prkn pathway", "pink1:prkn pathway ordureau\u00a0a", "pathway ordureau\u00a0a et\u00a0al.", "2015 sauve v", "sauve v et al.", "2022 . ubiquitin chains", ". ubiquitin chains on", "ubiquitin chains on prkn", "chains on prkn ubiquitinated", "on prkn ubiquitinated substrates", "prkn ubiquitinated substrates recruit", "ubiquitinated substrates recruit cargo", "substrates recruit cargo receptors", "recruit cargo receptors such", "cargo receptors such as", "receptors such as sqstm1", "as sqstm1 p62", "p62 and optn", "and optn linking the", "optn linking the ubiquitinated", "linking the ubiquitinated substrates", "the ubiquitinated substrates to", "ubiquitinated substrates to the", "substrates to the microtubule", "to the microtubule associated", "the microtubule associated proteins", "microtubule associated proteins 1a/1b", "associated proteins 1a/1b light", "proteins 1a/1b light chain", "1a/1b light chain 3", "chain 3 lc3", "map1lc3 heo", "heo lm et al.", "2015 lazarou m", "lazarou m et al.", "al. 2015 .", "2015 . the recruitment", ". the recruitment of", "the recruitment of both", "recruitment of both map1lc3", "both map1lc3 lc3", "lc3 complexes and", "complexes and the autophagy", "and the autophagy proteins", "the autophagy proteins 5", "autophagy proteins 5 and", "proteins 5 and 12", "and 12 atg5:", "12 atg5: atg12", "atg5: atg12 complex", "atg12 complex to", "complex to the autophagosome", "to the autophagosome membrane", "the autophagosome membrane promotes", "autophagosome membrane promotes autophagosome", "membrane promotes autophagosome formation.", "promotes autophagosome formation. the", "autophagosome formation. the mitochondrion", "formation. the mitochondrion is", "the mitochondrion is engulfed", "mitochondrion is engulfed after", "is engulfed after the", "engulfed after the isolation", "after the isolation membrane", "the isolation membrane grows", "isolation membrane grows to", "membrane grows to a", "grows to a sufficient", "to a sufficient size", "a sufficient size to", "sufficient size to engulf", "size to engulf the", "to engulf the mitochondrion.", "engulf the mitochondrion. once", "the mitochondrion. once autophagic", "mitochondrion. once autophagic vesicle", "once autophagic vesicle formation", "autophagic vesicle formation is", "vesicle formation is complete", "is complete vesicle", "complete vesicle fusion", "vesicle fusion with lysosomes", "fusion with lysosomes occurs", "with lysosomes occurs to", "lysosomes occurs to form", "occurs to form autophagolysosomes", "to form autophagolysosomes in", "form autophagolysosomes in which", "autophagolysosomes in which the", "in which the lysosomal", "which the lysosomal hydrolases", "lysosomal hydrolases cathepsins", "hydrolases cathepsins and", "and lipases degrade", "lipases degrade the", "degrade the intra autophagosomal", "the intra autophagosomal content.", "intra autophagosomal content. cathepsin", "autophagosomal content. cathepsin also", "content. cathepsin also degrades", "cathepsin also degrades lc3", "also degrades lc3 on", "degrades lc3 on the", "lc3 on the intra", "on the intra autophagosomal", "the intra autophagosomal surface", "intra autophagosomal surface of", "autophagosomal surface of the", "surface of the autophagic", "of the autophagic vesicle.", "this is the process of", "is the process of selective", "the process of selective removal", "process of selective removal of", "of selective removal of damaged", "selective removal of damaged mitochondria", "removal of damaged mitochondria by", "of damaged mitochondria by autophagosomes", "damaged mitochondria by autophagosomes and", "mitochondria by autophagosomes and subsequent", "by autophagosomes and subsequent catabolism", "autophagosomes and subsequent catabolism by", "and subsequent catabolism by lysosomes.", "subsequent catabolism by lysosomes. in", "catabolism by lysosomes. in healthy", "by lysosomes. in healthy mitochondria", "lysosomes. in healthy mitochondria pten", "in healthy mitochondria pten induced", "healthy mitochondria pten induced putative", "mitochondria pten induced putative kinase", "pten induced putative kinase 1", "putative kinase 1 pink1", "1 pink1 is", "pink1 is imported to", "is imported to the inner", "imported to the inner mitochondrial", "to the inner mitochondrial membrane", "inner mitochondrial membrane presumably", "mitochondrial membrane presumably through", "membrane presumably through the", "presumably through the tom/tim complex.", "through the tom/tim complex. the", "the tom/tim complex. the tim", "tom/tim complex. the tim complex", "complex. the tim complex associated", "the tim complex associated protease", "complex associated protease mitochondrial", "associated protease mitochondrial mpp", "mitochondrial mpp cleaves pink1", "mpp cleaves pink1 mitochondrial", "cleaves pink1 mitochondrial targeting sequence", "mitochondrial targeting sequence mts", "targeting sequence mts .", "sequence mts . pink1", "mts . pink1 may be", ". pink1 may be cleaved", "pink1 may be cleaved by", "may be cleaved by the", "be cleaved by the inner", "cleaved by the inner membrane", "by the inner membrane presenilin", "the inner membrane presenilin associated", "inner membrane presenilin associated rhomboid", "membrane presenilin associated rhomboid like", "presenilin associated rhomboid like protease", "rhomboid like protease parl", "protease parl and", "parl and ultimately proteolytically", "and ultimately proteolytically degraded. loss", "ultimately proteolytically degraded. loss of", "proteolytically degraded. loss of membrane", "degraded. loss of membrane potential", "loss of membrane potential in", "of membrane potential in damaged", "membrane potential in damaged mitochondria", "potential in damaged mitochondria prevents", "in damaged mitochondria prevents the", "damaged mitochondria prevents the import", "mitochondria prevents the import of", "prevents the import of pink1", "the import of pink1 which", "import of pink1 which accumulates", "of pink1 which accumulates on\u00a0the", "pink1 which accumulates on\u00a0the mitochondrial\u00a0outer", "which accumulates on\u00a0the mitochondrial\u00a0outer membrane", "on\u00a0the mitochondrial\u00a0outer membrane mom", "membrane mom of", "mom of the defective", "of the defective mitochondria. activation", "the defective mitochondria. activation of", "defective mitochondria. activation of pink1", "mitochondria. activation of pink1 at", "activation of pink1 at mom\u00a0is", "of pink1 at mom\u00a0is achieved", "pink1 at mom\u00a0is achieved via\u00a0dimerization", "at mom\u00a0is achieved via\u00a0dimerization mediated", "mom\u00a0is achieved via\u00a0dimerization mediated trans", "achieved via\u00a0dimerization mediated trans autophosphorylation", "via\u00a0dimerization mediated trans autophosphorylation of", "mediated trans autophosphorylation of pink1", "trans autophosphorylation of pink1 at", "autophosphorylation of pink1 at multiple", "of pink1 at multiple sites", "pink1 at multiple sites including", "at multiple sites including s228", "multiple sites including s228 and", "sites including s228 and s402", "s228 and s402 okatsu\u00a0k", "and s402 okatsu\u00a0k et", "s402 okatsu\u00a0k et al.", "okatsu\u00a0k et al. 2012", "al. 2012 2013", "2012 2013 aerts l", "2013 aerts l et al.", "l et al. 2015", "et al. 2015 rasool", "al. 2015 rasool s", "2015 rasool s et al.", "s et al. 2018", "al. 2018 2022", "2018 2022 gan", "2022 gan zy et", "zy et al. 2022", "et al. 2022 .", "al. 2022 . activated", "2022 . activated pink1 phosphorylates", ". activated pink1 phosphorylates s65", "activated pink1 phosphorylates s65 of", "pink1 phosphorylates s65 of ubiquitin", "s65 of ubiquitin ub", "ubiquitin ub on", "ub on mom proteins", "on mom proteins which leads", "mom proteins which leads to", "proteins which leads to increased", "which leads to increased recruitment", "leads to increased recruitment of", "to increased recruitment of the", "increased recruitment of the e3", "recruitment of the e3 ubiquitin", "of the e3 ubiquitin ligase", "the e3 ubiquitin ligase parkin", "ubiquitin ligase parkin prkn", "parkin prkn to", "prkn to damaged mitochondria", "to damaged mitochondria koyano", "damaged mitochondria koyano f", "mitochondria koyano f et", "f et al. 2014", "al. 2014 shiba", "2014 shiba fukushima k", "shiba fukushima k et al.", "k et al. 2014", "al. 2014 ordureau\u00a0a", "ordureau\u00a0a et\u00a0al. 2015 .", "et\u00a0al. 2015 . activated", "2015 . activated pink1 also", ". activated pink1 also phosphorylates", "activated pink1 also phosphorylates prkn", "pink1 also phosphorylates prkn at", "also phosphorylates prkn at s65", "phosphorylates prkn at s65 in", "prkn at s65 in the", "at s65 in the n", "s65 in the n terminal", "in the n terminal ub", "the n terminal ub like", "n terminal ub like domain", "terminal ub like domain inducing", "ub like domain inducing the", "like domain inducing the e3", "domain inducing the e3 ligase", "inducing the e3 ligase activity", "the e3 ligase activity of", "e3 ligase activity of prkn", "activity of prkn kondapalli", "of prkn kondapalli et", "prkn kondapalli et al.", "kondapalli et al. 2012", "al. 2012 kazlauskaite", "2012 kazlauskaite a et", "a et al. 2015", "al. 2015 ordureau\u00a0a", "2015 . activated prkn promotes", ". activated prkn promotes the", "activated prkn promotes the ubiquitination", "prkn promotes the ubiquitination of", "promotes the ubiquitination of mitochondrial", "the ubiquitination of mitochondrial substrates", "ubiquitination of mitochondrial substrates including", "of mitochondrial substrates including mitofusin", "mitochondrial substrates including mitofusin 1", "substrates including mitofusin 1 and", "including mitofusin 1 and 2", "1 and 2 mfn1", "2 mfn1 2", "mfn1 2 and", "2 and the voltage", "and the voltage dependent anion", "the voltage dependent anion channel", "voltage dependent anion channel 1", "dependent anion channel 1 and", "anion channel 1 and 3", "1 and 3 vdac1", "3 vdac1 3", "vdac1 3 . the", "3 . the e3 ligase", ". the e3 ligase activity", "ligase activity of prkn generates", "activity of prkn generates ub", "of prkn generates ub moieties", "prkn generates ub moieties for", "generates ub moieties for pink1", "ub moieties for pink1 mediated", "moieties for pink1 mediated phosphorylation", "for pink1 mediated phosphorylation of", "pink1 mediated phosphorylation of ub", "mediated phosphorylation of ub thus", "phosphorylation of ub thus leading", "of ub thus leading to", "ub thus leading to a", "thus leading to a feedforward", "leading to a feedforward loop", "to a feedforward loop in", "a feedforward loop in the", "feedforward loop in the pink1:prkn", "loop in the pink1:prkn pathway", "the pink1:prkn pathway ordureau\u00a0a", "pink1:prkn pathway ordureau\u00a0a et\u00a0al.", "et\u00a0al. 2015 sauve", "2015 sauve v et", "v et al. 2022", "al. 2022 . ubiquitin", "2022 . ubiquitin chains on", ". ubiquitin chains on prkn", "ubiquitin chains on prkn ubiquitinated", "chains on prkn ubiquitinated substrates", "on prkn ubiquitinated substrates recruit", "prkn ubiquitinated substrates recruit cargo", "ubiquitinated substrates recruit cargo receptors", "substrates recruit cargo receptors such", "recruit cargo receptors such as", "cargo receptors such as sqstm1", "such as sqstm1 p62", "sqstm1 p62 and", "p62 and optn linking", "and optn linking the ubiquitinated", "optn linking the ubiquitinated substrates", "linking the ubiquitinated substrates to", "the ubiquitinated substrates to the", "ubiquitinated substrates to the microtubule", "substrates to the microtubule associated", "to the microtubule associated proteins", "the microtubule associated proteins 1a/1b", "microtubule associated proteins 1a/1b light", "associated proteins 1a/1b light chain", "proteins 1a/1b light chain 3", "light chain 3 lc3", "3 lc3 map1lc3", "map1lc3 heo lm", "lm et al. 2015", "al. 2015 lazarou", "2015 lazarou m et", "m et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the recruitment of", ". the recruitment of both", "the recruitment of both map1lc3", "of both map1lc3 lc3", "map1lc3 lc3 complexes", "lc3 complexes and the", "complexes and the autophagy proteins", "and the autophagy proteins 5", "the autophagy proteins 5 and", "autophagy proteins 5 and 12", "5 and 12 atg5:", "and 12 atg5: atg12", "atg5: atg12 complex to", "atg12 complex to the", "complex to the autophagosome membrane", "to the autophagosome membrane promotes", "the autophagosome membrane promotes autophagosome", "autophagosome membrane promotes autophagosome formation.", "membrane promotes autophagosome formation. the", "promotes autophagosome formation. the mitochondrion", "autophagosome formation. the mitochondrion is", "formation. the mitochondrion is engulfed", "the mitochondrion is engulfed after", "mitochondrion is engulfed after the", "is engulfed after the isolation", "engulfed after the isolation membrane", "after the isolation membrane grows", "the isolation membrane grows to", "isolation membrane grows to a", "membrane grows to a sufficient", "grows to a sufficient size", "to a sufficient size to", "a sufficient size to engulf", "sufficient size to engulf the", "size to engulf the mitochondrion.", "to engulf the mitochondrion. once", "engulf the mitochondrion. once autophagic", "the mitochondrion. once autophagic vesicle", "mitochondrion. once autophagic vesicle formation", "once autophagic vesicle formation is", "autophagic vesicle formation is complete", "formation is complete vesicle", "is complete vesicle fusion", "complete vesicle fusion with", "vesicle fusion with lysosomes occurs", "fusion with lysosomes occurs to", "with lysosomes occurs to form", "lysosomes occurs to form autophagolysosomes", "occurs to form autophagolysosomes in", "to form autophagolysosomes in which", "form autophagolysosomes in which the", "autophagolysosomes in which the lysosomal", "in which the lysosomal hydrolases", "the lysosomal hydrolases cathepsins", "lysosomal hydrolases cathepsins and", "hydrolases cathepsins and lipases", "cathepsins and lipases degrade", "and lipases degrade the", "lipases degrade the intra", "degrade the intra autophagosomal content.", "the intra autophagosomal content. cathepsin", "intra autophagosomal content. cathepsin also", "autophagosomal content. cathepsin also degrades", "content. cathepsin also degrades lc3", "cathepsin also degrades lc3 on", "also degrades lc3 on the", "degrades lc3 on the intra", "lc3 on the intra autophagosomal", "on the intra autophagosomal surface", "the intra autophagosomal surface of", "intra autophagosomal surface of the", "autophagosomal surface of the autophagic", "surface of the autophagic vesicle." ] }, { "record_id": "GLY_000594_1_1001", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5218920", "r hsa", "hsa 5218920", "r hsa 5218920" ] }, { "record_id": "GLY_000594_1_1001", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "vegfr2 mediated", "mediated vascular", "vascular permeability", "vegfr2 mediated vascular", "mediated vascular permeability", "vegfr2 mediated vascular permeability", "the free", "free radical", "radical nitric", "nitric oxide", "produced by", "by endothelial", "endothelial no", "no synthase", "is an", "an important", "important vasoactive", "vasoactive substance", "substance in", "in normal", "normal vascular", "vascular biology", "biology and", "and pathophysiology.", "pathophysiology. it", "it plays", "plays an", "important role", "role in", "in vascular", "vascular functions", "functions such", "such as", "as vascular", "vascular dilation", "dilation and", "and angiogenesis", "murohara et", "et al.", "al. 1998", "ziche at", "at al.", "al. 1997", "1997 .", ". no", "no has", "has been", "been reported", "reported to", "to be", "be a", "a downstream", 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in a", "activation in a ras", "in a ras guanine", "a ras guanine nucleotide", "ras guanine nucleotide exchange", "guanine nucleotide exchange factor", "exchange factor gef", "gef independent mechanism.", "independent mechanism. it rather", "mechanism. it rather relies", "it rather relies on", "rather relies on modulating", "relies on modulating the", "on modulating the regulation", "modulating the regulation of", "the regulation of ras", "regulation of ras gtpase", "of ras gtpase activating", "ras gtpase activating protein", "activating protein gap", "gap than regulation", "than regulation of ras", "regulation of ras gefs", "ras gefs wu", "gefs wu et", "wu et al. 2003", "et al. 2003 .", "vegfr2 stimulates erk not via", "stimulates erk not via grb2", "erk not via grb2 sos", "not via grb2 sos ras", "grb2 sos ras but", "sos ras but via", "ras but via py1175", "but via py1175 dependent phosphorylation", "via py1175 dependent phosphorylation of", "py1175 dependent phosphorylation of plc", "dependent phosphorylation of plc gamma", "phosphorylation of plc gamma and", "of plc gamma and subsequent", "plc gamma and subsequent activation", "gamma and subsequent activation of", "and subsequent activation of pkcs.", "subsequent activation of pkcs. pkc", "activation of pkcs. pkc plays", "of pkcs. pkc plays an", "pkcs. pkc plays an important", "pkc plays an important mediatory", "plays an important mediatory role", "an important mediatory role in", "important mediatory role in the", "mediatory role in the proliferative", "role in the proliferative ras/raf/mek/erk", "in the proliferative ras/raf/mek/erk pathway.", "the proliferative ras/raf/mek/erk pathway. pkc", "proliferative ras/raf/mek/erk pathway. pkc alpha", "ras/raf/mek/erk pathway. pkc alpha can", "pathway. pkc alpha can intersect", "pkc alpha can intersect the", "alpha can intersect the ras/raf/mek/erk", "can intersect the ras/raf/mek/erk cascade", "intersect the ras/raf/mek/erk cascade at", "the ras/raf/mek/erk cascade at the", "ras/raf/mek/erk cascade at the level", "cascade at the level of", "at the level of ras", "level of ras clark", "of ras clark et", "ras clark et al.", "et al. 2004 or", "al. 2004 or downstream", "2004 or downstream of", "or downstream of ras through", "downstream of ras through direct", "of ras through direct phosphorylation", "ras through direct phosphorylation of", "through direct phosphorylation of raf", "phosphorylation of raf kolch", "of raf kolch et", "raf kolch et al.", "kolch et al. 1993 .", "et al. 1993 . vegf", "al. 1993 . vegf stimulation", "1993 . vegf stimulation leads", ". vegf stimulation leads to", "vegf stimulation leads to ras", "stimulation leads to ras activation", "leads to ras activation in", "to ras activation in a", "ras activation in a ras", "activation in a ras guanine", "in a ras guanine nucleotide", "a ras guanine nucleotide exchange", "ras guanine nucleotide exchange factor", "nucleotide exchange factor gef", "factor gef independent", "gef independent mechanism. it", "independent mechanism. it rather relies", "mechanism. it rather relies on", "it rather relies on modulating", "rather relies on modulating the", "relies on modulating the regulation", "on modulating the regulation of", "modulating the regulation of ras", "the regulation of ras gtpase", "regulation of ras gtpase activating", "of ras gtpase activating protein", "gtpase activating protein gap", "protein gap than", "gap than regulation of", "than regulation of ras gefs", "of ras gefs wu", "ras gefs wu et", "gefs wu et al.", "wu et al. 2003 ." ] }, { "record_id": "GLY_000594_1_1003", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5221030", "r hsa", "hsa 5221030", "r hsa 5221030" ] }, { "record_id": "GLY_000594_1_1003", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tet1 2", "2 3", "3 and", "and tdg", "tdg demethylate", "demethylate dna", "tet1 2 3", "2 3 and", "3 and tdg", "and tdg demethylate", "tdg demethylate dna", "tet1 2 3 and", "2 3 and tdg", "3 and tdg demethylate", "and tdg demethylate dna", "tet1 2 3 and tdg", "2 3 and tdg demethylate", "3 and tdg demethylate dna", "about 2", "2 6%", "6% of", "of all", "all cytosine", "cytosine residues", "residues and", "and 70", "70 80%", "80% of", "of cytosine", "residues in", "in cg", "cg dinucleotides", "dinucleotides in", "in mammalian", "mammalian cells", "cells are", "are methylated", "methylated at", "at the", "the 5", "5 position", "position of", "of the", "the pyrimidine", "pyrimidine ring.", "ring. the", "the cytosine", "residues are", "methylated by", "by dna", "dna methyltransferases", "methyltransferases after", "after dna", "dna replication", "replication and", "and can", "can be", "be demethylated", "demethylated by", "by passive", "passive dilution", "dilution during", "during subsequent", "subsequent replication", "replication or", "or by", "by active", "active modification", "modification of", "5 methylcytosine", "methylcytosine base.", "base. cytosine", "cytosine demethylation", "demethylation is", "is developmentally", "developmentally regulated:", "regulated: one", "one wave", "wave of", "of demethylation", "demethylation occurs", "occurs in", "in primordial", "primordial germ", "germ cells", "cells and", "and one", "wave occurs", "occurs by", "active demethylation", "demethylation in", "in the", "the male", "male pronucleus", "pronucleus after", "after fertilization.
              some", "fertilization.
              some mechanisms", "mechanisms of", "of active", "demethylation remain", "remain controversial", "however progressive", "progressive oxidation", "oxidation of", "the methyl", "methyl group", "group of", "of 5", "methylcytosine followed", "followed by", "by base", "base excision", "excision by", "by thymine", "thymine dna", "dna glycosylase", "has been", "been reproducibly", "reproducibly demonstrated", "demonstrated in", "in vivo", "reviewed in", "in wu", "wu and", "and zhang", "zhang 2011", "franchini et", "et al", "al 2012", "cadet and", "and wagner", "wagner 2013", "kohli and", "zhang 2013", "ponnaluri et", "et al.", "al. 2013", "rasmussen and", "and helin", "helin 2016", "2016 .", ". ten", "ten eleven", "eleven translocation", "translocation proteins", "proteins tet1", "and tet3", "tet3 are", "are dioxygenases", "dioxygenases that", "that first", "first oxidize", "oxidize 5", "methylcytosine to", "to 5", "5 hydroxymethylcytosine", "5 hmc", "tahiliani et", "al. 2009", "ito et", "al. 2010", "which is", "is found", "found in", "in significant", "significant quantities", "quantities and", "and specific", "specific genomic", "genomic locations", "locations in", "in stem", "stem cells", "and neurons", "kinney and", "and pradhan", "pradhan 2013", "2013 .", ". tet", "tet proteins", "proteins can", "can further", "further oxidize", "hmc to", "5 formylcytosine", "5 fc", "and then", "then 5", "5 carboxylcytosine", "5 cac", "he et", "al. 2011", "2011 .", ". g:5", "g:5 fc", "fc and", "and g:5", "g:5 cac", "cac base", "base pairs", "pairs are", "are recognized", "recognized by", "by tdg", "which excises", "excises the", "fc or", "or 5", "cac and", "and leaves", "leaves an", "an abasic", "abasic site.
              tet1", "site.
              tet1 in", "in mouse", "mouse is", "is expressed", "expressed in", "in neurons", "neurons and", "and its", "its expression", "expression depends", "depends on", "on neuronal", "neuronal activity", "guo et", "kaas et", "zhang et", ". tet1", "tet1 is", "is also", "also found", "in embryonic", "embryonic stem", "ficz et", "koh et", "wu et", "and in", "cells of", "of mice", "where it", "it plays", "plays a", "a role", "role in", "in erasure", "erasure of", "of imprinting", "yamaguchi et", ". tet3", "tet3 is", "in oocytes", "oocytes and", "and zygotes", "zygotes of", "mice and", "and is", "is required", "required for", "for demethylation", "gu et", "iqbal et", ". tet2", "tet2 is", "is the", "the most", "most highly", "highly expressed", "expressed tet", "tet family", "family protein", "protein in", "in hemopoietic", "hemopoietic stem", "and appears", "appears to", "to act", "act as", "as a", "a tumor", "tumor suppressor.", "suppressor. tet2", "also expressed", "about 2 6%", "2 6% of", "6% of all", "of all cytosine", "all cytosine residues", "cytosine residues and", "residues and 70", "and 70 80%", "70 80% of", "80% of cytosine", "of cytosine residues", "cytosine residues in", "residues in cg", "in cg dinucleotides", "cg dinucleotides in", "dinucleotides in mammalian", "in mammalian cells", "mammalian cells are", "cells are methylated", "are methylated at", "methylated at the", "at the 5", "the 5 position", "5 position of", "position of the", "of the pyrimidine", "the pyrimidine ring.", "pyrimidine ring. the", "ring. the cytosine", "the cytosine residues", "cytosine residues are", "residues are methylated", "are methylated by", "methylated by dna", "by dna methyltransferases", "dna methyltransferases after", "methyltransferases after dna", "after dna replication", "dna replication and", "replication and can", "and can be", "can be demethylated", "be demethylated by", "demethylated by passive", "by passive dilution", "passive dilution during", "dilution during subsequent", "during subsequent replication", "subsequent replication or", "replication or by", "or by active", "by active modification", "active modification of", "modification of the", "of the 5", "the 5 methylcytosine", "5 methylcytosine base.", "methylcytosine base. cytosine", "base. cytosine demethylation", "cytosine demethylation is", "demethylation is developmentally", "is developmentally regulated:", "developmentally regulated: one", "regulated: one wave", "one wave of", "wave of demethylation", "of demethylation occurs", "demethylation occurs in", "occurs in primordial", "in primordial germ", "primordial germ cells", "germ cells and", "cells and one", "and one wave", "one wave occurs", "wave occurs by", "occurs by active", "by active demethylation", "active demethylation in", "demethylation in the", "in the male", "the male pronucleus", "male pronucleus after", "pronucleus after fertilization.
              some", "after fertilization.
              some mechanisms", "fertilization.
              some mechanisms of", "mechanisms of active", "of active demethylation", "active demethylation remain", "demethylation remain controversial", "controversial however", "however progressive oxidation", "progressive oxidation of", "oxidation of the", "of the methyl", "the methyl group", "methyl group of", "group of 5", "of 5 methylcytosine", "5 methylcytosine followed", "methylcytosine followed by", "followed by base", "by base excision", "base excision by", "excision by thymine", "by thymine dna", "thymine dna glycosylase", "glycosylase tdg", "tdg has", "has been reproducibly", "been reproducibly demonstrated", "reproducibly demonstrated in", "demonstrated in vivo", "vivo reviewed", "reviewed in wu", "in wu and", "wu and zhang", "and zhang 2011", "2011 franchini", "franchini et al", "et al 2012", "2012 cadet", "cadet and wagner", "and wagner 2013", "2013 kohli", "kohli and zhang", "and zhang 2013", "2013 ponnaluri", "ponnaluri et al.", "et al. 2013", "2013 rasmussen", "rasmussen and helin", "and helin 2016", "helin 2016 .", "2016 . ten", ". ten eleven", "ten eleven translocation", "eleven translocation proteins", "translocation proteins tet1", "tet1 tet2", "tet2 and", "and tet3 are", "tet3 are dioxygenases", "are dioxygenases that", "dioxygenases that first", "that first oxidize", "first oxidize 5", "oxidize 5 methylcytosine", "5 methylcytosine to", "methylcytosine to 5", "to 5 hydroxymethylcytosine", "hydroxymethylcytosine 5", "tahiliani et al.", "et al. 2009", "2009 ito", "ito et al.", "et al. 2010", "which is found", "is found in", "found in significant", "in significant quantities", "significant quantities and", "quantities and specific", "and specific genomic", "specific genomic locations", "genomic locations in", "locations in stem", "in stem cells", "stem cells and", "cells and neurons", "neurons kinney", "kinney and pradhan", "and pradhan 2013", "pradhan 2013 .", "2013 . tet", ". tet proteins", "tet proteins can", "proteins can further", "can further oxidize", "further oxidize 5", "oxidize 5 hmc", "5 hmc to", "hmc to 5", "to 5 formylcytosine", "formylcytosine 5", "and then 5", "then 5 carboxylcytosine", "carboxylcytosine 5", "he et al.", "et al. 2011", "2011 ito", "al. 2011 .", "2011 . g:5", ". g:5 fc", "g:5 fc and", "fc and g:5", "and g:5 cac", "g:5 cac base", "cac base pairs", "base pairs are", "pairs are recognized", "are recognized by", "recognized by tdg", "tdg which", "which excises the", "excises the 5", "the 5 fc", "5 fc or", "fc or 5", "or 5 cac", "5 cac and", "cac and leaves", "and leaves an", "leaves an abasic", "an abasic site.
              tet1", "abasic site.
              tet1 in", "site.
              tet1 in mouse", "in mouse is", "mouse is expressed", "is expressed in", "expressed in neurons", "in neurons and", "neurons and its", "and its expression", "its expression depends", "expression depends on", "depends on neuronal", "on neuronal activity", "activity guo", "guo et al.", "2011 kaas", "kaas et al.", "2013 zhang", "zhang et al.", "al. 2013 .", "2013 . tet1", ". tet1 is", "tet1 is also", "is also found", "also found in", "found in embryonic", "in embryonic stem", "embryonic stem cells", "cells ficz", "ficz et al.", "2011 koh", "koh et al.", "2011 wu", "wu et al.", "2011 and", "and in primordial", "germ cells of", "cells of mice", "mice where", "where it plays", "it plays a", "plays a role", "a role in", "role in erasure", "in erasure of", "erasure of imprinting", "imprinting yamaguchi", "yamaguchi et al.", "2013 . tet3", ". tet3 is", "tet3 is expressed", "expressed in oocytes", "in oocytes and", "oocytes and zygotes", "and zygotes of", "zygotes of mice", "of mice and", "mice and is", "and is required", "is required for", "required for demethylation", "for demethylation in", "pronucleus gu", "gu et al.", "2011 iqbal", "iqbal et al.", "2011 . tet2", ". tet2 is", "tet2 is the", "is the most", "the most highly", "most highly expressed", "highly expressed tet", "expressed tet family", "tet family protein", "family protein in", "protein in hemopoietic", "in hemopoietic stem", "hemopoietic stem cells", "cells and appears", "and appears to", "appears to act", "to act as", "act as a", "as a tumor", "a tumor suppressor.", "tumor suppressor. tet2", "suppressor. tet2 is", "tet2 is also", "is also expressed", "also expressed in", "expressed in embryonic", "cells koh", "about 2 6% of", "2 6% of all", "6% of all cytosine", "of all cytosine residues", "all cytosine residues and", "cytosine residues and 70", "residues and 70 80%", "and 70 80% of", "70 80% of cytosine", "80% of cytosine residues", "of cytosine residues in", "cytosine residues in cg", "residues in cg dinucleotides", "in cg dinucleotides in", "cg dinucleotides in mammalian", "dinucleotides in mammalian cells", "in mammalian cells are", "mammalian cells are methylated", "cells are methylated at", "are methylated at the", "methylated at the 5", "at the 5 position", "the 5 position of", "5 position of the", "position of the pyrimidine", "of the pyrimidine ring.", "the pyrimidine ring. the", "pyrimidine ring. the cytosine", "ring. the cytosine residues", "the cytosine residues are", "cytosine residues are methylated", "residues are methylated by", "are methylated by dna", "methylated by dna methyltransferases", "by dna methyltransferases after", "dna methyltransferases after dna", "methyltransferases after dna replication", "after dna replication and", "dna replication and can", "replication and can be", "and can be demethylated", "can be demethylated by", "be demethylated by passive", "demethylated by passive dilution", "by passive dilution during", "passive dilution during subsequent", "dilution during subsequent replication", "during subsequent replication or", "subsequent replication or by", "replication or by active", "or by active modification", "by active modification of", "active modification of the", "modification of the 5", "of the 5 methylcytosine", "the 5 methylcytosine base.", "5 methylcytosine base. cytosine", "methylcytosine base. cytosine demethylation", "base. cytosine demethylation is", "cytosine demethylation is developmentally", "demethylation is developmentally regulated:", "is developmentally regulated: one", "developmentally regulated: one wave", "regulated: one wave of", "one wave of demethylation", "wave of demethylation occurs", "of demethylation occurs in", "demethylation occurs in primordial", "occurs in primordial germ", "in primordial germ cells", "primordial germ cells and", "germ cells and one", "cells and one wave", "and one wave occurs", "one wave occurs by", "wave occurs by active", "occurs by active demethylation", "by active demethylation in", "active demethylation in the", "demethylation in the male", "in the male pronucleus", "the male pronucleus after", "male pronucleus after fertilization.
              some", "pronucleus after fertilization.
              some mechanisms", "after fertilization.
              some mechanisms of", "fertilization.
              some mechanisms of active", "mechanisms of active demethylation", "of active demethylation remain", "active demethylation remain controversial", "remain controversial however", "controversial however progressive", "however progressive oxidation of", "progressive oxidation of the", "oxidation of the methyl", "of the methyl group", "the methyl group of", "methyl group of 5", "group of 5 methylcytosine", "of 5 methylcytosine followed", "5 methylcytosine followed by", "methylcytosine followed by base", "followed by base excision", "by base excision by", "base excision by thymine", "excision by thymine dna", "by thymine dna glycosylase", "dna glycosylase tdg", "tdg has been", "has been reproducibly demonstrated", "been reproducibly demonstrated in", "reproducibly demonstrated in vivo", "in vivo reviewed", "vivo reviewed in", "reviewed in wu and", "in wu and zhang", "wu and zhang 2011", "zhang 2011 franchini", "2011 franchini et", "franchini et al 2012", "al 2012 cadet", "2012 cadet and", "cadet and wagner 2013", "wagner 2013 kohli", "2013 kohli and", "kohli and zhang 2013", "zhang 2013 ponnaluri", "2013 ponnaluri et", "ponnaluri et al. 2013", "al. 2013 rasmussen", "2013 rasmussen and", "rasmussen and helin 2016", "and helin 2016 .", "helin 2016 . ten", "2016 . ten eleven", ". ten eleven translocation", "ten eleven translocation proteins", "eleven translocation proteins tet1", "proteins tet1 tet2", "tet2 and tet3", "and tet3 are dioxygenases", "tet3 are dioxygenases that", "are dioxygenases that first", "dioxygenases that first oxidize", "that first oxidize 5", "first oxidize 5 methylcytosine", "oxidize 5 methylcytosine to", "5 methylcytosine to 5", "methylcytosine to 5 hydroxymethylcytosine", "5 hydroxymethylcytosine 5", "hydroxymethylcytosine 5 hmc", "hmc tahiliani", "tahiliani et al. 2009", "al. 2009 ito", "2009 ito et", "ito et al. 2010", "2010 which", "which is found in", "is found in significant", "found in significant quantities", "in significant quantities and", "significant quantities and specific", "quantities and specific genomic", "and specific genomic locations", "specific genomic locations in", "genomic locations in stem", "locations in stem cells", "in stem cells and", "stem cells and neurons", "and neurons kinney", "neurons kinney and", "kinney and pradhan 2013", "and pradhan 2013 .", "pradhan 2013 . tet", "2013 . tet proteins", ". tet proteins can", "tet proteins can further", "proteins can further oxidize", "can further oxidize 5", "further oxidize 5 hmc", "oxidize 5 hmc to", "5 hmc to 5", "hmc to 5 formylcytosine", "5 formylcytosine 5", "formylcytosine 5 fc", "5 fc and", "fc and then", "and then 5 carboxylcytosine", "5 carboxylcytosine 5", "carboxylcytosine 5 cac", "cac he", "he et al. 2011", "al. 2011 ito", "2011 ito et", "ito et al. 2011", "et al. 2011 .", "al. 2011 . g:5", "2011 . g:5 fc", ". g:5 fc and", "g:5 fc and g:5", "fc and g:5 cac", "and g:5 cac base", "g:5 cac base pairs", "cac base pairs are", "base pairs are recognized", "pairs are recognized by", "are recognized by tdg", "by tdg which", "tdg which excises", "which excises the 5", "excises the 5 fc", "the 5 fc or", "5 fc or 5", "fc or 5 cac", "or 5 cac and", "5 cac and leaves", "cac and leaves an", "and leaves an abasic", "leaves an abasic site.
              tet1", "an abasic site.
              tet1 in", "abasic site.
              tet1 in mouse", "site.
              tet1 in mouse is", "in mouse is expressed", "mouse is expressed in", "is expressed in neurons", "expressed in neurons and", "in neurons and its", "neurons and its expression", "and its expression depends", "its expression depends on", "expression depends on neuronal", "depends on neuronal activity", "neuronal activity guo", "activity guo et", "guo et al. 2011", "al. 2011 kaas", "2011 kaas et", "kaas et al. 2013", "al. 2013 zhang", "2013 zhang et", "zhang et al. 2013", "et al. 2013 .", "al. 2013 . tet1", "2013 . tet1 is", ". tet1 is also", "tet1 is also found", "is also found in", "also found in embryonic", "found in embryonic stem", "in embryonic stem cells", "stem cells ficz", "cells ficz et", "ficz et al. 2011", "al. 2011 koh", "2011 koh et", "koh et al. 2011", "al. 2011 wu", "2011 wu et", "wu et al. 2011", "al. 2011 and", "2011 and in", "and in primordial germ", "primordial germ cells of", "germ cells of mice", "of mice where", "mice where it", "where it plays a", "it plays a role", "plays a role in", "a role in erasure", "role in erasure of", "in erasure of imprinting", "of imprinting yamaguchi", "imprinting yamaguchi et", "yamaguchi et al. 2013", "al. 2013 . tet3", "2013 . tet3 is", ". tet3 is expressed", "tet3 is expressed in", "is expressed in oocytes", "expressed in oocytes and", "in oocytes and zygotes", "oocytes and zygotes of", "and zygotes of mice", "zygotes of mice and", "of mice and is", "mice and is required", "and is required for", "is required for demethylation", "required for demethylation in", "for demethylation in the", "male pronucleus gu", "pronucleus gu et", "gu et al. 2011", "al. 2011 iqbal", "2011 iqbal et", "iqbal et al. 2011", "al. 2011 . tet2", "2011 . tet2 is", ". tet2 is the", "tet2 is the most", "is the most highly", "the most highly expressed", "most highly expressed tet", "highly expressed tet family", "expressed tet family protein", "tet family protein in", "family protein in hemopoietic", "protein in hemopoietic stem", "in hemopoietic stem cells", "hemopoietic stem cells and", "stem cells and appears", "cells and appears to", "and appears to act", "appears to act as", "to act as a", "act as a tumor", "as a tumor suppressor.", "a tumor suppressor. tet2", "tumor suppressor. tet2 is", "suppressor. tet2 is also", "tet2 is also expressed", "is also expressed in", "also expressed in embryonic", "expressed in embryonic stem", "stem cells koh", "cells koh et", "about 2 6% of all", "2 6% of all cytosine", "6% of all cytosine residues", "of all cytosine residues and", "all cytosine residues and 70", "cytosine residues and 70 80%", "residues and 70 80% of", "and 70 80% of cytosine", "70 80% of cytosine residues", "80% of cytosine residues in", "of cytosine residues in cg", "cytosine residues in cg dinucleotides", "residues in cg dinucleotides in", "in cg dinucleotides in mammalian", "cg dinucleotides in mammalian cells", "dinucleotides in mammalian cells are", "in mammalian cells are methylated", "mammalian cells are methylated at", "cells are methylated at the", "are methylated at the 5", "methylated at the 5 position", "at the 5 position of", "the 5 position of the", "5 position of the pyrimidine", "position of the pyrimidine ring.", "of the pyrimidine ring. the", "the pyrimidine ring. the cytosine", "pyrimidine ring. the cytosine residues", "ring. the cytosine residues are", "the cytosine residues are methylated", "cytosine residues are methylated by", "residues are methylated by dna", "are methylated by dna methyltransferases", "methylated by dna methyltransferases after", "by dna methyltransferases after dna", "dna methyltransferases after dna replication", "methyltransferases after dna replication and", "after dna replication and can", "dna replication and can be", "replication and can be demethylated", "and can be demethylated by", "can be demethylated by passive", "be demethylated by passive dilution", "demethylated by passive dilution during", "by passive dilution during subsequent", "passive dilution during subsequent replication", "dilution during subsequent replication or", "during subsequent replication or by", "subsequent replication or by active", "replication or by active modification", "or by active modification of", "by active modification of the", "active modification of the 5", "modification of the 5 methylcytosine", "of the 5 methylcytosine base.", "the 5 methylcytosine base. cytosine", "5 methylcytosine base. cytosine demethylation", "methylcytosine base. cytosine demethylation is", "base. cytosine demethylation is developmentally", "cytosine demethylation is developmentally regulated:", "demethylation is developmentally regulated: one", "is developmentally regulated: one wave", "developmentally regulated: one wave of", "regulated: one wave of demethylation", "one wave of demethylation occurs", "wave of demethylation occurs in", "of demethylation occurs in primordial", "demethylation occurs in primordial germ", "occurs in primordial germ cells", "in primordial germ cells and", "primordial germ cells and one", "germ cells and one wave", "cells and one wave occurs", "and one wave occurs by", "one wave occurs by active", "wave occurs by active demethylation", "occurs by active demethylation in", "by active demethylation in the", "active demethylation in the male", "demethylation in the male pronucleus", "in the male pronucleus after", "the male pronucleus after fertilization.
              some", "male pronucleus after fertilization.
              some mechanisms", "pronucleus after fertilization.
              some mechanisms of", "after fertilization.
              some mechanisms of active", "fertilization.
              some mechanisms of active demethylation", "mechanisms of active demethylation remain", "of active demethylation remain controversial", "demethylation remain controversial however", "remain controversial however progressive", "controversial however progressive oxidation", "however progressive oxidation of the", "progressive oxidation of the methyl", "oxidation of the methyl group", "of the methyl group of", "the methyl group of 5", "methyl group of 5 methylcytosine", "group of 5 methylcytosine followed", "of 5 methylcytosine followed by", "5 methylcytosine followed by base", "methylcytosine followed by base excision", "followed by base excision by", "by base excision by thymine", "base excision by thymine dna", "excision by thymine dna glycosylase", "thymine dna glycosylase tdg", "glycosylase tdg has", "tdg has been reproducibly", "has been reproducibly demonstrated in", "been reproducibly demonstrated in vivo", "demonstrated in vivo reviewed", "in vivo reviewed in", "vivo reviewed in wu", "reviewed in wu and zhang", "in wu and zhang 2011", "and zhang 2011 franchini", "zhang 2011 franchini et", "2011 franchini et al", "et al 2012 cadet", "al 2012 cadet and", "2012 cadet and wagner", "and wagner 2013 kohli", "wagner 2013 kohli and", "2013 kohli and zhang", "and zhang 2013 ponnaluri", "zhang 2013 ponnaluri et", "2013 ponnaluri et al.", "et al. 2013 rasmussen", "al. 2013 rasmussen and", "2013 rasmussen and helin", "rasmussen and helin 2016 .", "and helin 2016 . ten", "helin 2016 . ten eleven", "2016 . ten eleven translocation", ". ten eleven translocation proteins", "ten eleven translocation proteins tet1", "translocation proteins tet1 tet2", "tet1 tet2 and", "tet2 and tet3 are", "and tet3 are dioxygenases that", "tet3 are dioxygenases that first", "are dioxygenases that first oxidize", "dioxygenases that first oxidize 5", "that first oxidize 5 methylcytosine", "first oxidize 5 methylcytosine to", "oxidize 5 methylcytosine to 5", "5 methylcytosine to 5 hydroxymethylcytosine", "to 5 hydroxymethylcytosine 5", "5 hydroxymethylcytosine 5 hmc", "5 hmc tahiliani", "hmc tahiliani et", "et al. 2009 ito", "al. 2009 ito et", "2009 ito et al.", "al. 2010 which", "2010 which is", "which is found in significant", "is found in significant quantities", "found in significant quantities and", "in significant quantities and specific", "significant quantities and specific genomic", "quantities and specific genomic locations", "and specific genomic locations in", "specific genomic locations in stem", "genomic locations in stem cells", "locations in stem cells and", "in stem cells and neurons", "cells and neurons kinney", "and neurons kinney and", "neurons kinney and pradhan", "kinney and pradhan 2013 .", "and pradhan 2013 . tet", "pradhan 2013 . tet proteins", "2013 . tet proteins can", ". tet proteins can further", "tet proteins can further oxidize", "proteins can further oxidize 5", "can further oxidize 5 hmc", "further oxidize 5 hmc to", "oxidize 5 hmc to 5", "5 hmc to 5 formylcytosine", "to 5 formylcytosine 5", "5 formylcytosine 5 fc", "5 fc and then", "fc and then 5", "then 5 carboxylcytosine 5", "5 carboxylcytosine 5 cac", "5 cac he", "cac he et", "et al. 2011 ito", "al. 2011 ito et", "2011 ito et al.", "ito et al. 2011 .", "et al. 2011 . g:5", "al. 2011 . g:5 fc", "2011 . g:5 fc and", ". g:5 fc and g:5", "g:5 fc and g:5 cac", "fc and g:5 cac base", "and g:5 cac base pairs", "g:5 cac base pairs are", "cac base pairs are recognized", "base pairs are recognized by", "pairs are recognized by tdg", "recognized by tdg which", "by tdg which excises", "tdg which excises the", "which excises the 5 fc", "excises the 5 fc or", "the 5 fc or 5", "5 fc or 5 cac", "fc or 5 cac and", "or 5 cac and leaves", "5 cac and leaves an", "cac and leaves an abasic", "and leaves an abasic site.
              tet1", "leaves an abasic site.
              tet1 in", "an abasic site.
              tet1 in mouse", "abasic site.
              tet1 in mouse is", "site.
              tet1 in mouse is expressed", "in mouse is expressed in", "mouse is expressed in neurons", "is expressed in neurons and", "expressed in neurons and its", "in neurons and its expression", "neurons and its expression depends", "and its expression depends on", "its expression depends on neuronal", "expression depends on neuronal activity", "on neuronal activity guo", "neuronal activity guo et", "activity guo et al.", "et al. 2011 kaas", "al. 2011 kaas et", "2011 kaas et al.", "et al. 2013 zhang", "al. 2013 zhang et", "2013 zhang et al.", "zhang et al. 2013 .", "et al. 2013 . tet1", "al. 2013 . tet1 is", "2013 . tet1 is also", ". tet1 is also found", "tet1 is also found in", "is also found in embryonic", "also found in embryonic stem", "found in embryonic stem cells", "embryonic stem cells ficz", "stem cells ficz et", "cells ficz et al.", "et al. 2011 koh", "al. 2011 koh et", "2011 koh et al.", "et al. 2011 wu", "al. 2011 wu et", "2011 wu et al.", "et al. 2011 and", "al. 2011 and in", "2011 and in primordial", "and in primordial germ cells", "in primordial germ cells of", "primordial germ cells of mice", "cells of mice where", "of mice where it", "mice where it plays", "where it plays a role", "it plays a role in", "plays a role in erasure", "a role in erasure of", "role in erasure of imprinting", "erasure of imprinting yamaguchi", "of imprinting yamaguchi et", "imprinting yamaguchi et al.", "yamaguchi et al. 2013 .", "et al. 2013 . tet3", "al. 2013 . tet3 is", "2013 . tet3 is expressed", ". tet3 is expressed in", "tet3 is expressed in oocytes", "is expressed in oocytes and", "expressed in oocytes and zygotes", "in oocytes and zygotes of", "oocytes and zygotes of mice", "and zygotes of mice and", "zygotes of mice and is", "of mice and is required", "mice and is required for", "and is required for demethylation", "is required for demethylation in", "required for demethylation in the", "for demethylation in the male", "the male pronucleus gu", "male pronucleus gu et", "pronucleus gu et al.", "et al. 2011 iqbal", "al. 2011 iqbal et", "2011 iqbal et al.", "iqbal et al. 2011 .", "et al. 2011 . tet2", "al. 2011 . tet2 is", "2011 . tet2 is the", ". tet2 is the most", "tet2 is the most highly", "is the most highly expressed", "the most highly expressed tet", "most highly expressed tet family", "highly expressed tet family protein", "expressed tet family protein in", "tet family protein in hemopoietic", "family protein in hemopoietic stem", "protein in hemopoietic stem cells", "in hemopoietic stem cells and", "hemopoietic stem cells and appears", "stem cells and appears to", "cells and appears to act", "and appears to act as", "appears to act as a", "to act as a tumor", "act as a tumor suppressor.", "as a tumor suppressor. tet2", "a tumor suppressor. tet2 is", "tumor suppressor. tet2 is also", "suppressor. tet2 is also expressed", "tet2 is also expressed in", "is also expressed in embryonic", "also expressed in embryonic stem", "expressed in embryonic stem cells", "embryonic stem cells koh", "stem cells koh et", "cells koh et al.", "koh et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1004", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5223345", "r hsa", "hsa 5223345", "r hsa 5223345" ] }, { "record_id": "GLY_000594_1_1004", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "miscellaneous transport", "transport and", "and binding", "binding events", "miscellaneous transport and", "transport and binding", "and binding events", "miscellaneous transport and binding", "transport and binding events", "miscellaneous transport and binding events", "this section", "section contains", "contains known", "known transport", "events that", "that as", "as of", "of yet", "yet cannot", "cannot be", "be placed", "placed in", "in exisiting", "exisiting pathways", "purves 2001", "he et", "et al.", "al. 2009", "rees et", "2009 .", "this section contains", "section contains known", "contains known transport", "known transport and", "binding events that", "events that as", "that as of", "as of yet", "of yet cannot", "yet cannot be", "cannot be placed", "be placed in", "placed in exisiting", "in exisiting pathways", "pathways purves", "2001 he", "he et al.", "et al. 2009", "2009 rees", "rees et al.", "al. 2009 .", "this section contains known", "section contains known transport", "contains known transport and", "known transport and binding", "and binding events that", "binding events that as", "events that as of", "that as of yet", "as of yet cannot", "of yet cannot be", "yet cannot be placed", "cannot be placed in", "be placed in exisiting", "placed in exisiting pathways", "exisiting pathways purves", "pathways purves 2001", "purves 2001 he", "2001 he et", "he et al. 2009", "al. 2009 rees", "2009 rees et", "rees et al. 2009", "et al. 2009 .", "this section contains known transport", "section contains known transport and", "contains known transport and binding", "known transport and binding events", "transport and binding events that", "and binding events that as", "binding events that as of", "events that as of yet", "that as of yet cannot", "as of yet cannot be", "of yet cannot be placed", "yet cannot be placed in", "cannot be placed in exisiting", "be placed in exisiting pathways", "in exisiting pathways purves", "exisiting pathways purves 2001", "purves 2001 he et", "2001 he et al.", "et al. 2009 rees", "al. 2009 rees et", "2009 rees et al.", "rees et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1005", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5334118", "r hsa", "hsa 5334118", "r hsa 5334118" ] }, { "record_id": "GLY_000594_1_1005", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dna methylation", "methylation of", "of cytosine", "cytosine is", "is catalyzed", "catalyzed by", "by a", "a family", "family of", "of dna", "dna methyltransferases", "dnmts :", ": dnmt1", "and dnmt3b", "dnmt3b transfer", "transfer methyl", "methyl groups", "groups from", "from s", "s adenosylmethionine", "adenosylmethionine to", "to cytosine", "producing 5", "5 methylcytosine", "methylcytosine and", "and homocysteine", "reviewed in", "in klose", "klose and", "and bird", "bird 2006", "ooi et", "et al.", "al. 2009", "jurkowska et", "al. 2011", "moore et", "al. 2013", "2013 .", "dnmt2 appears", "appears to", "to methylate", "methylate rna", "rna rather", "rather than", "than dna.", "the first", "first enzyme", "enzyme discovered", "preferentially methylates", "methylates hemimethylated", "hemimethylated cg", "cg motifs", "motifs that", "that are", "are produced", "produced by", "by replication", "template strand", "strand methylated", "synthesized strand", "strand unmethylated", "unmethylated .", ". thus", "thus it", "it maintains", "maintains existing", "existing methylation", "methylation through", "through cell", "cell division.", "division. dnmt3a", "dnmt3a and", "dnmt3b catalyze", "catalyze de", "de novo", "novo methylation", "methylation at", "at unmethylated", "unmethylated sites", "sites that", "that include", "include both", "both cg", "cg dinucleotides", "dinucleotides and", "and non", "non cg", "cg motifs.
              dna", "motifs.
              dna from", "from adult", "adult humans", "humans contains", "contains about", "about 0.76", "0.76 to", "to 1.00", "1.00 mole", "mole percent", "percent 5", "ehrlich et", "al. 1982", ". methylation", "dna occurs", "occurs at", "at cytosines", "cytosines that", "are mainly", "mainly located", "located in", "in cg", "cg dinucleotides.", "dinucleotides. cg", "dinucleotides are", "are unevenly", "unevenly distributed", "distributed in", "in the", "the genome.", "genome. promoter", "promoter regions", "regions tend", "tend to", "to have", "have a", "a high", "high cg", "cg content", "forming so", "so called", "called cg", "cg islands", "while the", "the cg", "content in", "the remaining", "remaining part", "part of", "of the", "the genome", "genome is", "is much", "much lower.", "lower. cgis", "cgis tend", "to be", "be unmethylated", "the majority", "majority of", "of cgs", "cgs outside", "outside cgis", "cgis are", "are methylated.", "methylated. methylation", "methylation in", "in promoters", "promoters and", "and first", "first exons", "exons tends", "tends to", "to repress", "repress transcription", "transcription while", "while methylation", "in gene", "gene bodies", "regions of", "of genes", "genes downstream", "downstream of", "the promoter", "promoter and", "first exon", "correlates with", "with transcription", "in ehrlich", "ehrlich and", "and lacey", "lacey 2013", "kulis et", ". proteins", "proteins such", "such as", "as mecp2", "mecp2 and", "and mbds", "mbds specifically", "specifically bind", "bind 5", "and may", "may recruit", "recruit other", "other factors.
              mammalian", "factors.
              mammalian development", "development has", "has two", "two major", "major episodes", "episodes of", "of genome", "genome wide", "wide demethylation", "demethylation and", "and remethylation", "in zhou", "zhou 2012", "guibert and", "and weber", "weber 2013", "hackett and", "and surani", "surani 2013", "dean 2014", "2014 .", ". in", "in mice", "mice about", "about 1", "1 day", "day after", "after fertilization", "fertilization the", "the paternal", "paternal genome", "is actively", "actively demethylated", "demethylated by", "by tet", "tet proteins", "proteins together", "together with", "with thymine", "thymine dna", "dna glycosylase", "glycosylase and", "and the", "the maternal", "maternal genome", "is demethylated", "by passive", "passive dilution", "dilution during", "during replication", "however methylation", "at imprinted", "imprinted sites", "sites is", "is maintained.", "maintained. the", "genome has", "has its", "its lowest", "lowest methylation", "methylation level", "level about", "about 3.5", "3.5 days", "days post", "post fertilization.", "fertilization. remethylation", "remethylation occurs", "occurs by", "by 6.5", "6.5 days", "fertilization. the", "the second", "second demethylation", "demethylation remethylation", "remethylation event", "event occurs", "occurs in", "in primordial", "primordial germ", "germ cells", "cells of", "the developing", "developing embryo", "embryo about", "about 12.5", "12.5 days", "fertilization. dnmt3a", "with the", "the non", "non catalytic", "catalytic dnmt3l", "play major", "major roles", "roles in", "the remethylation", "remethylation events", "in chen", "chen and", "and chan", "chan 2014", ". how", "how the", "the methyltransferases", "methyltransferases are", "are directed", "directed to", "to particular", "particular regions", "genome remains", "remains an", "an area", "area of", "of active", "active research.", "research. the", "the mechanisms", "mechanisms at", "at each", "each locus", "locus may", "may differ", "differ in", "in detail", "detail but", "but a", "a connection", "connection between", "between histone", "histone modifications", "modifications and", "and dna", "methylation has", "has been", "been observed", "in rose", "rose and", "and klose", "klose 2014", "methylation of cytosine", "of cytosine is", "cytosine is catalyzed", "is catalyzed by", "catalyzed by a", "by a family", "a family of", "family of dna", "of dna methyltransferases", "methyltransferases dnmts", "dnmts : dnmt1", "dnmt1 dnmt3a", "and dnmt3b transfer", "dnmt3b transfer methyl", "transfer methyl groups", "methyl groups from", "groups from s", "from s adenosylmethionine", "s adenosylmethionine to", "adenosylmethionine to cytosine", "cytosine producing", "producing 5 methylcytosine", "5 methylcytosine and", "methylcytosine and homocysteine", "homocysteine reviewed", "reviewed in klose", "in klose and", "klose and bird", "and bird 2006", "2006 ooi", "ooi et al.", "et al. 2009", "2009 jurkowska", "jurkowska et al.", "et al. 2011", "2011 moore", "moore et al.", "et al. 2013", "al. 2013 .", ". dnmt2", "dnmt2 appears to", "appears to methylate", "to methylate rna", "methylate rna rather", "rna rather than", "rather than dna.", "dna. dnmt1", "dnmt1 the", "the first enzyme", "first enzyme discovered", "discovered preferentially", "preferentially methylates hemimethylated", "methylates hemimethylated cg", "hemimethylated cg motifs", "cg motifs that", "motifs that are", "that are produced", "are produced by", "produced by replication", "replication template", "template strand methylated", "methylated synthesized", "synthesized strand unmethylated", "strand unmethylated .", "unmethylated . thus", ". thus it", "thus it maintains", "it maintains existing", "maintains existing methylation", "existing methylation through", "methylation through cell", "through cell division.", "cell division. dnmt3a", "division. dnmt3a and", "dnmt3a and dnmt3b", "and dnmt3b catalyze", "dnmt3b catalyze de", "catalyze de novo", "de novo methylation", "novo methylation at", "methylation at unmethylated", "at unmethylated sites", "unmethylated sites that", "sites that include", "that include both", "include both cg", "both cg dinucleotides", "cg dinucleotides and", "dinucleotides and non", "and non cg", "non cg motifs.
              dna", "cg motifs.
              dna from", "motifs.
              dna from adult", "from adult humans", "adult humans contains", "humans contains about", "contains about 0.76", "about 0.76 to", "0.76 to 1.00", "to 1.00 mole", "1.00 mole percent", "mole percent 5", "percent 5 methylcytosine", "methylcytosine ehrlich", "ehrlich et al.", "et al. 1982", "1982 reviewed", "2009 moore", "2013 . methylation", ". methylation of", "methylation of dna", "of dna occurs", "dna occurs at", "occurs at cytosines", "at cytosines that", "cytosines that are", "that are mainly", "are mainly located", "mainly located in", "located in cg", "in cg dinucleotides.", "cg dinucleotides. cg", "dinucleotides. cg dinucleotides", "cg dinucleotides are", "dinucleotides are unevenly", "are unevenly distributed", "unevenly distributed in", "distributed in the", "in the genome.", "the genome. promoter", "genome. promoter regions", "promoter regions tend", "regions tend to", "tend to have", "to have a", "have a high", "a high cg", "high cg content", "content forming", "forming so called", "so called cg", "called cg islands", "islands cgis", "while the cg", "the cg content", "cg content in", "content in the", "in the remaining", "the remaining part", "remaining part of", "part of the", "of the genome", "the genome is", "genome is much", "is much lower.", "much lower. cgis", "lower. cgis tend", "cgis tend to", "tend to be", "to be unmethylated", "unmethylated while", "while the majority", "the majority of", "majority of cgs", "of cgs outside", "cgs outside cgis", "outside cgis are", "cgis are methylated.", "are methylated. methylation", "methylated. methylation in", "methylation in promoters", "in promoters and", "promoters and first", "and first exons", "first exons tends", "exons tends to", "tends to repress", "to repress transcription", "repress transcription while", "transcription while methylation", "while methylation in", "methylation in gene", "in gene bodies", "bodies regions", "regions of genes", "of genes downstream", "genes downstream of", "downstream of the", "of the promoter", "the promoter and", "promoter and first", "and first exon", "exon correlates", "correlates with transcription", "transcription reviewed", "reviewed in ehrlich", "in ehrlich and", "ehrlich and lacey", "and lacey 2013", "2013 kulis", "kulis et al.", "2013 . proteins", ". proteins such", "proteins such as", "such as mecp2", "as mecp2 and", "mecp2 and mbds", "and mbds specifically", "mbds specifically bind", "specifically bind 5", "bind 5 methylcytosine", "methylcytosine and may", "and may recruit", "may recruit other", "recruit other factors.
              mammalian", "other factors.
              mammalian development", "factors.
              mammalian development has", "development has two", "has two major", "two major episodes", "major episodes of", "episodes of genome", "of genome wide", "genome wide demethylation", "wide demethylation and", "demethylation and remethylation", "remethylation reviewed", "reviewed in zhou", "in zhou 2012", "2012 guibert", "guibert and weber", "and weber 2013", "2013 hackett", "hackett and surani", "and surani 2013", "2013 dean", "dean 2014 .", "2014 . in", ". in mice", "in mice about", "mice about 1", "about 1 day", "1 day after", "day after fertilization", "after fertilization the", "fertilization the paternal", "the paternal genome", "paternal genome is", "genome is actively", "is actively demethylated", "actively demethylated by", "demethylated by tet", "by tet proteins", "tet proteins together", "proteins together with", "together with thymine", "with thymine dna", "thymine dna glycosylase", "dna glycosylase and", "glycosylase and the", "and the maternal", "the maternal genome", "maternal genome is", "genome is demethylated", "is demethylated by", "demethylated by passive", "by passive dilution", "passive dilution during", "dilution during replication", "replication however", "however methylation at", "methylation at imprinted", "at imprinted sites", "imprinted sites is", "sites is maintained.", "is maintained. the", "maintained. the genome", "the genome has", "genome has its", "has its lowest", "its lowest methylation", "lowest methylation level", "methylation level about", "level about 3.5", "about 3.5 days", "3.5 days post", "days post fertilization.", "post fertilization. remethylation", "fertilization. remethylation occurs", "remethylation occurs by", "occurs by 6.5", "by 6.5 days", "6.5 days post", "post fertilization. the", "fertilization. the second", "the second demethylation", "second demethylation remethylation", "demethylation remethylation event", "remethylation event occurs", "event occurs in", "occurs in primordial", "in primordial germ", "primordial germ cells", "germ cells of", "cells of the", "of the developing", "the developing embryo", "developing embryo about", "embryo about 12.5", "about 12.5 days", "12.5 days post", "post fertilization. dnmt3a", "fertilization. dnmt3a and", "dnmt3b together", "together with the", "with the non", "the non catalytic", "non catalytic dnmt3l", "dnmt3l play", "play major roles", "major roles in", "roles in the", "in the remethylation", "the remethylation events", "events reviewed", "reviewed in chen", "in chen and", "chen and chan", "and chan 2014", "chan 2014 .", "2014 . how", ". how the", "how the methyltransferases", "the methyltransferases are", "methyltransferases are directed", "are directed to", "directed to particular", "to particular regions", "particular regions of", "regions of the", "the genome remains", "genome remains an", "remains an area", "an area of", "area of active", "of active research.", "active research. the", "research. the mechanisms", "the mechanisms at", "mechanisms at each", "at each locus", "each locus may", "locus may differ", "may differ in", "differ in detail", "in detail but", "detail but a", "but a connection", "a connection between", "connection between histone", "between histone modifications", "histone modifications and", "modifications and dna", "and dna methylation", "dna methylation has", "methylation has been", "has been observed", "observed reviewed", "reviewed in rose", "in rose and", "rose and klose", "and klose 2014", "klose 2014 .", "methylation of cytosine is", "of cytosine is catalyzed", "cytosine is catalyzed by", "is catalyzed by a", "catalyzed by a family", "by a family of", "a family of dna", "family of dna methyltransferases", "dna methyltransferases dnmts", "methyltransferases dnmts :", ": dnmt1 dnmt3a", "and dnmt3b transfer methyl", "dnmt3b transfer methyl groups", "transfer methyl groups from", "methyl groups from s", "groups from s adenosylmethionine", "from s adenosylmethionine to", "s adenosylmethionine to cytosine", "to cytosine producing", "cytosine producing 5", "producing 5 methylcytosine and", "5 methylcytosine and homocysteine", "and homocysteine reviewed", "homocysteine reviewed in", "reviewed in klose and", "in klose and bird", "klose and bird 2006", "bird 2006 ooi", "2006 ooi et", "ooi et al. 2009", "al. 2009 jurkowska", "2009 jurkowska et", "jurkowska et al. 2011", "al. 2011 moore", "2011 moore et", "moore et al. 2013", "et al. 2013 .", "2013 . dnmt2", ". dnmt2 appears", "dnmt2 appears to methylate", "appears to methylate rna", "to methylate rna rather", "methylate rna rather than", "rna rather than dna.", "than dna. dnmt1", "dnmt1 the first", "the first enzyme discovered", "enzyme discovered preferentially", "discovered preferentially methylates", "preferentially methylates hemimethylated cg", "methylates hemimethylated cg motifs", "hemimethylated cg motifs that", "cg motifs that are", "motifs that are produced", "that are produced by", "are produced by replication", "by replication template", "replication template strand", "strand methylated synthesized", "methylated synthesized strand", "synthesized strand unmethylated .", "strand unmethylated . thus", "unmethylated . thus it", ". thus it maintains", "thus it maintains existing", "it maintains existing methylation", "maintains existing methylation through", "existing methylation through cell", "methylation through cell division.", "through cell division. dnmt3a", "cell division. dnmt3a and", "division. dnmt3a and dnmt3b", "dnmt3a and dnmt3b catalyze", "and dnmt3b catalyze de", "dnmt3b catalyze de novo", "catalyze de novo methylation", "de novo methylation at", "novo methylation at unmethylated", "methylation at unmethylated sites", "at unmethylated sites that", "unmethylated sites that include", "sites that include both", "that include both cg", "include both cg dinucleotides", "both cg dinucleotides and", "cg dinucleotides and non", "dinucleotides and non cg", "and non cg motifs.
              dna", "non cg motifs.
              dna from", "cg motifs.
              dna from adult", "motifs.
              dna from adult humans", "from adult humans contains", "adult humans contains about", "humans contains about 0.76", "contains about 0.76 to", "about 0.76 to 1.00", "0.76 to 1.00 mole", "to 1.00 mole percent", "1.00 mole percent 5", "mole percent 5 methylcytosine", "5 methylcytosine ehrlich", "methylcytosine ehrlich et", "ehrlich et al. 1982", "al. 1982 reviewed", "1982 reviewed in", "al. 2009 moore", "2009 moore et", "al. 2013 . methylation", "2013 . methylation of", ". methylation of dna", "methylation of dna occurs", "of dna occurs at", "dna occurs at cytosines", "occurs at cytosines that", "at cytosines that are", "cytosines that are mainly", "that are mainly located", "are mainly located in", "mainly located in cg", "located in cg dinucleotides.", "in cg dinucleotides. cg", "cg dinucleotides. cg dinucleotides", "dinucleotides. cg dinucleotides are", "cg dinucleotides are unevenly", "dinucleotides are unevenly distributed", "are unevenly distributed in", "unevenly distributed in the", "distributed in the genome.", "in the genome. promoter", "the genome. promoter regions", "genome. promoter regions tend", "promoter regions tend to", "regions tend to have", "tend to have a", "to have a high", "have a high cg", "a high cg content", "cg content forming", "content forming so", "forming so called cg", "so called cg islands", "cg islands cgis", "cgis while", "while the cg content", "the cg content in", "cg content in the", "content in the remaining", "in the remaining part", "the remaining part of", "remaining part of the", "part of the genome", "of the genome is", "the genome is much", "genome is much lower.", "is much lower. cgis", "much lower. cgis tend", "lower. cgis tend to", "cgis tend to be", "tend to be unmethylated", "be unmethylated while", "unmethylated while the", "while the majority of", "the majority of cgs", "majority of cgs outside", "of cgs outside cgis", "cgs outside cgis are", "outside cgis are methylated.", "cgis are methylated. methylation", "are methylated. methylation in", "methylated. methylation in promoters", "methylation in promoters and", "in promoters and first", "promoters and first exons", "and first exons tends", "first exons tends to", "exons tends to repress", "tends to repress transcription", "to repress transcription while", "repress transcription while methylation", "transcription while methylation in", "while methylation in gene", "methylation in gene bodies", "gene bodies regions", "bodies regions of", "regions of genes downstream", "of genes downstream of", "genes downstream of the", "downstream of the promoter", "of the promoter and", "the promoter and first", "promoter and first exon", "first exon correlates", "exon correlates with", "with transcription reviewed", "transcription reviewed in", "reviewed in ehrlich and", "in ehrlich and lacey", "ehrlich and lacey 2013", "lacey 2013 kulis", "2013 kulis et", "kulis et al. 2013", "al. 2013 . proteins", "2013 . proteins such", ". proteins such as", "proteins such as mecp2", "such as mecp2 and", "as mecp2 and mbds", "mecp2 and mbds specifically", "and mbds specifically bind", "mbds specifically bind 5", "specifically bind 5 methylcytosine", "bind 5 methylcytosine and", "5 methylcytosine and may", "methylcytosine and may recruit", "and may recruit other", "may recruit other factors.
              mammalian", "recruit other factors.
              mammalian development", "other factors.
              mammalian development has", "factors.
              mammalian development has two", "development has two major", "has two major episodes", "two major episodes of", "major episodes of genome", "episodes of genome wide", "of genome wide demethylation", "genome wide demethylation and", "wide demethylation and remethylation", "and remethylation reviewed", "remethylation reviewed in", "reviewed in zhou 2012", "zhou 2012 guibert", "2012 guibert and", "guibert and weber 2013", "weber 2013 hackett", "2013 hackett and", "hackett and surani 2013", "surani 2013 dean", "2013 dean 2014", "dean 2014 . in", "2014 . in mice", ". in mice about", "in mice about 1", "mice about 1 day", "about 1 day after", "1 day after fertilization", "day after fertilization the", "after fertilization the paternal", "fertilization the paternal genome", "the paternal genome is", "paternal genome is actively", "genome is actively demethylated", "is actively demethylated by", "actively demethylated by tet", "demethylated by tet proteins", "by tet proteins together", "tet proteins together with", "proteins together with thymine", "together with thymine dna", "with thymine dna glycosylase", "thymine dna glycosylase and", "dna glycosylase and the", "glycosylase and the maternal", "and the maternal genome", "the maternal genome is", "maternal genome is demethylated", "genome is demethylated by", "is demethylated by passive", "demethylated by passive dilution", "by passive dilution during", "passive dilution during replication", "during replication however", "replication however methylation", "however methylation at imprinted", "methylation at imprinted sites", "at imprinted sites is", "imprinted sites is maintained.", "sites is maintained. the", "is maintained. the genome", "maintained. the genome has", "the genome has its", "genome has its lowest", "has its lowest methylation", "its lowest methylation level", "lowest methylation level about", "methylation level about 3.5", "level about 3.5 days", "about 3.5 days post", "3.5 days post fertilization.", "days post fertilization. remethylation", "post fertilization. remethylation occurs", "fertilization. remethylation occurs by", "remethylation occurs by 6.5", "occurs by 6.5 days", "by 6.5 days post", "6.5 days post fertilization.", "days post fertilization. the", "post fertilization. the second", "fertilization. the second demethylation", "the second demethylation remethylation", "second demethylation remethylation event", "demethylation remethylation event occurs", "remethylation event occurs in", "event occurs in primordial", "occurs in primordial germ", "in primordial germ cells", "primordial germ cells of", "germ cells of the", "cells of the developing", "of the developing embryo", "the developing embryo about", "developing embryo about 12.5", "embryo about 12.5 days", "about 12.5 days post", "12.5 days post fertilization.", "days post fertilization. dnmt3a", "post fertilization. dnmt3a and", "fertilization. dnmt3a and dnmt3b", "and dnmt3b together", "dnmt3b together with", "together with the non", "with the non catalytic", "the non catalytic dnmt3l", "catalytic dnmt3l play", "dnmt3l play major", "play major roles in", "major roles in the", "roles in the remethylation", "in the remethylation events", "remethylation events reviewed", "events reviewed in", "reviewed in chen and", "in chen and chan", "chen and chan 2014", "and chan 2014 .", "chan 2014 . how", "2014 . how the", ". how the methyltransferases", "how the methyltransferases are", "the methyltransferases are directed", "methyltransferases are directed to", "are directed to particular", "directed to particular regions", "to particular regions of", "particular regions of the", "regions of the genome", "of the genome remains", "the genome remains an", "genome remains an area", "remains an area of", "an area of active", "area of active research.", "of active research. the", "active research. the mechanisms", "research. the mechanisms at", "the mechanisms at each", "mechanisms at each locus", "at each locus may", "each locus may differ", "locus may differ in", "may differ in detail", "differ in detail but", "in detail but a", "detail but a connection", "but a connection between", "a connection between histone", "connection between histone modifications", "between histone modifications and", "histone modifications and dna", "modifications and dna methylation", "and dna methylation has", "dna methylation has been", "methylation has been observed", "been observed reviewed", "observed reviewed in", "reviewed in rose and", "in rose and klose", "rose and klose 2014", "and klose 2014 .", "methylation of cytosine is catalyzed", "of cytosine is catalyzed by", "cytosine is catalyzed by a", "is catalyzed by a family", "catalyzed by a family of", "by a family of dna", "a family of dna methyltransferases", "of dna methyltransferases dnmts", "dna methyltransferases dnmts :", "methyltransferases dnmts : dnmt1", "dnmts : dnmt1 dnmt3a", "dnmt1 dnmt3a and", "dnmt3a and dnmt3b transfer", "and dnmt3b transfer methyl groups", "dnmt3b transfer methyl groups from", "transfer methyl groups from s", "methyl groups from s adenosylmethionine", "groups from s adenosylmethionine to", "from s adenosylmethionine to cytosine", "adenosylmethionine to cytosine producing", "to cytosine producing 5", "cytosine producing 5 methylcytosine", "producing 5 methylcytosine and homocysteine", "methylcytosine and homocysteine reviewed", "and homocysteine reviewed in", "homocysteine reviewed in klose", "reviewed in klose and bird", "in klose and bird 2006", "and bird 2006 ooi", "bird 2006 ooi et", "2006 ooi et al.", "et al. 2009 jurkowska", "al. 2009 jurkowska et", "2009 jurkowska et al.", "et al. 2011 moore", "al. 2011 moore et", "2011 moore et al.", "moore et al. 2013 .", "al. 2013 . dnmt2", "2013 . dnmt2 appears", ". dnmt2 appears to", "dnmt2 appears to methylate rna", "appears to methylate rna rather", "to methylate rna rather than", "methylate rna rather than dna.", "rather than dna. dnmt1", "dna. dnmt1 the", "dnmt1 the first enzyme", "first enzyme discovered preferentially", "enzyme discovered preferentially methylates", "discovered preferentially methylates hemimethylated", "preferentially methylates hemimethylated cg motifs", "methylates hemimethylated cg motifs that", "hemimethylated cg motifs that are", "cg motifs that are produced", "motifs that are produced by", "that are produced by replication", "produced by replication template", "by replication template strand", "replication template strand methylated", "template strand methylated synthesized", "strand methylated synthesized strand", "methylated synthesized strand unmethylated", "synthesized strand unmethylated . thus", "strand unmethylated . thus it", "unmethylated . thus it maintains", ". thus it maintains existing", "thus it maintains existing methylation", "it maintains existing methylation through", "maintains existing methylation through cell", "existing methylation through cell division.", "methylation through cell division. dnmt3a", "through cell division. dnmt3a and", "cell division. dnmt3a and dnmt3b", "division. dnmt3a and dnmt3b catalyze", "dnmt3a and dnmt3b catalyze de", "and dnmt3b catalyze de novo", "dnmt3b catalyze de novo methylation", "catalyze de novo methylation at", "de novo methylation at unmethylated", "novo methylation at unmethylated sites", "methylation at unmethylated sites that", "at unmethylated sites that include", "unmethylated sites that include both", "sites that include both cg", "that include both cg dinucleotides", "include both cg dinucleotides and", "both cg dinucleotides and non", "cg dinucleotides and non cg", "dinucleotides and non cg motifs.
              dna", "and non cg motifs.
              dna from", "non cg motifs.
              dna from adult", "cg motifs.
              dna from adult humans", "motifs.
              dna from adult humans contains", "from adult humans contains about", "adult humans contains about 0.76", "humans contains about 0.76 to", "contains about 0.76 to 1.00", "about 0.76 to 1.00 mole", "0.76 to 1.00 mole percent", "to 1.00 mole percent 5", "1.00 mole percent 5 methylcytosine", "percent 5 methylcytosine ehrlich", "5 methylcytosine ehrlich et", "methylcytosine ehrlich et al.", "et al. 1982 reviewed", "al. 1982 reviewed in", "1982 reviewed in klose", "et al. 2009 moore", "al. 2009 moore et", "2009 moore et al.", "et al. 2013 . methylation", "al. 2013 . methylation of", "2013 . methylation of dna", ". methylation of dna occurs", "methylation of dna occurs at", "of dna occurs at cytosines", "dna occurs at cytosines that", "occurs at cytosines that are", "at cytosines that are mainly", "cytosines that are mainly located", "that are mainly located in", "are mainly located in cg", "mainly located in cg dinucleotides.", "located in cg dinucleotides. cg", "in cg dinucleotides. cg dinucleotides", "cg dinucleotides. cg dinucleotides are", "dinucleotides. cg dinucleotides are unevenly", "cg dinucleotides are unevenly distributed", "dinucleotides are unevenly distributed in", "are unevenly distributed in the", "unevenly distributed in the genome.", "distributed in the genome. promoter", "in the genome. promoter regions", "the genome. promoter regions tend", "genome. promoter regions tend to", "promoter regions tend to have", "regions tend to have a", "tend to have a high", "to have a high cg", "have a high cg content", "high cg content forming", "cg content forming so", "content forming so called", "forming so called cg islands", "called cg islands cgis", "cgis while the", "while the cg content in", "the cg content in the", "cg content in the remaining", "content in the remaining part", "in the remaining part of", "the remaining part of the", "remaining part of the genome", "part of the genome is", "of the genome is much", "the genome is much lower.", "genome is much lower. cgis", "is much lower. cgis tend", "much lower. cgis tend to", "lower. cgis tend to be", "cgis tend to be unmethylated", "to be unmethylated while", "be unmethylated while the", "unmethylated while the majority", "while the majority of cgs", "the majority of cgs outside", "majority of cgs outside cgis", "of cgs outside cgis are", "cgs outside cgis are methylated.", "outside cgis are methylated. methylation", "cgis are methylated. methylation in", "are methylated. methylation in promoters", "methylated. methylation in promoters and", "methylation in promoters and first", "in promoters and first exons", "promoters and first exons tends", "and first exons tends to", "first exons tends to repress", "exons tends to repress transcription", "tends to repress transcription while", "to repress transcription while methylation", "repress transcription while methylation in", "transcription while methylation in gene", "while methylation in gene bodies", "in gene bodies regions", "gene bodies regions of", "bodies regions of genes", "regions of genes downstream of", "of genes downstream of the", "genes downstream of the promoter", "downstream of the promoter and", "of the promoter and first", "the promoter and first exon", "and first exon correlates", "first exon correlates with", "exon correlates with transcription", "correlates with transcription reviewed", "with transcription reviewed in", "transcription reviewed in ehrlich", "reviewed in ehrlich and lacey", "in ehrlich and lacey 2013", "and lacey 2013 kulis", "lacey 2013 kulis et", "2013 kulis et al.", "kulis et al. 2013 .", "et al. 2013 . proteins", "al. 2013 . proteins such", "2013 . proteins such as", ". proteins such as mecp2", "proteins such as mecp2 and", "such as mecp2 and mbds", "as mecp2 and mbds specifically", "mecp2 and mbds specifically bind", "and mbds specifically bind 5", "mbds specifically bind 5 methylcytosine", "specifically bind 5 methylcytosine and", "bind 5 methylcytosine and may", "5 methylcytosine and may recruit", "methylcytosine and may recruit other", "and may recruit other factors.
              mammalian", "may recruit other factors.
              mammalian development", "recruit other factors.
              mammalian development has", "other factors.
              mammalian development has two", "factors.
              mammalian development has two major", "development has two major episodes", "has two major episodes of", "two major episodes of genome", "major episodes of genome wide", "episodes of genome wide demethylation", "of genome wide demethylation and", "genome wide demethylation and remethylation", "demethylation and remethylation reviewed", "and remethylation reviewed in", "remethylation reviewed in zhou", "in zhou 2012 guibert", "zhou 2012 guibert and", "2012 guibert and weber", "and weber 2013 hackett", "weber 2013 hackett and", "2013 hackett and surani", "and surani 2013 dean", "surani 2013 dean 2014", "2013 dean 2014 .", "dean 2014 . in mice", "2014 . in mice about", ". in mice about 1", "in mice about 1 day", "mice about 1 day after", "about 1 day after fertilization", "1 day after fertilization the", "day after fertilization the paternal", "after fertilization the paternal genome", "fertilization the paternal genome is", "the paternal genome is actively", "paternal genome is actively demethylated", "genome is actively demethylated by", "is actively demethylated by tet", "actively demethylated by tet proteins", "demethylated by tet proteins together", "by tet proteins together with", "tet proteins together with thymine", "proteins together with thymine dna", "together with thymine dna glycosylase", "with thymine dna glycosylase and", "thymine dna glycosylase and the", "dna glycosylase and the maternal", "glycosylase and the maternal genome", "and the maternal genome is", "the maternal genome is demethylated", "maternal genome is demethylated by", "genome is demethylated by passive", "is demethylated by passive dilution", "demethylated by passive dilution during", "by passive dilution during replication", "dilution during replication however", "during replication however methylation", "replication however methylation at", "however methylation at imprinted sites", "methylation at imprinted sites is", "at imprinted sites is maintained.", "imprinted 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reviewed in chen", "reviewed in chen and chan", "in chen and chan 2014", "chen and chan 2014 .", "and chan 2014 . how", "chan 2014 . how the", "2014 . how the methyltransferases", ". how the methyltransferases are", "how the methyltransferases are directed", "the methyltransferases are directed to", "methyltransferases are directed to particular", "are directed to particular regions", "directed to particular regions of", "to particular regions of the", "particular regions of the genome", "regions of the genome remains", "of the genome remains an", "the genome remains an area", "genome remains an area of", "remains an area of active", "an area of active research.", "area of active research. the", "of active research. the mechanisms", "active research. the mechanisms at", "research. the mechanisms at each", "the mechanisms at each locus", "mechanisms at each locus may", "at each locus may differ", "each locus may differ in", "locus may differ in detail", "may differ in detail but", 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              defects in acth", "and carbohydrates.

              defects in acth can", "carbohydrates.

              defects in acth can cause", "in acth can cause obesity", "can cause obesity mim:601665", "obesity mim:601665 resulting", "mim:601665 resulting in excessive", "601665 resulting in excessive", "resulting in excessive accumulation of", "in excessive accumulation of body", "excessive accumulation of body fat", "of body fat challis", "body fat challis et", "fat challis et al.", "et al. 2002 millington", "al. 2002 millington 2013", "2002 millington 2013 .", "millington 2013 . defects in", "2013 . defects in acth", ". defects in acth can", "defects in acth can also", "in acth can also cause", "acth can also cause pro", "can also cause pro opiomelanocortinin", "also cause pro opiomelanocortinin deficiency", "pro opiomelanocortinin deficiency pomcd", "deficiency pomcd mim:609734", "pomcd mim:609734 where", "mim:609734 where affected individuals", "609734 where affected individuals", "where affected individuals present early", "affected individuals present early onset", "individuals present early onset obesity", "early onset obesity adrenal", "onset obesity adrenal insufficiency", "obesity adrenal insufficiency and", "adrenal insufficiency and red hair", "and red hair krude", "red hair krude et", "hair krude et al.", "et al. 1998 krude", "al. 1998 krude et", "1998 krude et al.", "krude et al. 2003 ." ] }, { "record_id": "GLY_000594_1_1016", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5602680", "r hsa", "hsa 5602680", "r hsa 5602680" ] }, { "record_id": "GLY_000594_1_1016", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "myd88 deficiency", "deficiency tlr5", "myd88 deficiency tlr5", "myeloid differentiation", "differentiation primary", "primary response", "is an", "an adaptor", "adaptor protein", "protein that", "that mediates", "mediates intracellular", "intracellular signaling", "signaling pathways", "pathways evoked", "evoked by", "by all", "all toll", "toll like", "like receptors", "except for", "for tlr3", "and several", "several interleukin", "interleukin 1", "1 receptors", "il 1rs", "medzhitov r", "r et", "et al.", "al. 1998", "1998 .", ". upon", "upon ligand", "ligand binding", "tlrs hetero", "or homodimerize", "homodimerize and", "and recruit", "recruit myd88", "myd88 through", "through their", "their respective", "respective tir", "tir domains.", "domains. then", "myd88 oligomerizes", "oligomerizes via", "via its", "its death", "death domain", "and tir", "tir domain", "domain and", "and interacts", "interacts with", "with the", "the interleukin", "1 receptor", "receptor associated", "associated kinases", "to form", "form the", "the myddosome", "myddosome complex", "motshwene pg", "pg et", "al. 2009", "lin sc", "sc et", "al. 2010", "2010 .", ". the", "complex transmits", "transmits the", "the signal", "signal leading", "leading to", "to activation", "activation of", "of transcription", "transcription factors", "factors such", "such as", "as nuclear", "nuclear factor", "factor kappab", "and activator", "activator protein", "protein 1", "ap1 .

              studies", ".

              studies have", "have identified", "identified patients", "patients with", "with autosomal", "autosomal recessive", "form of", "of myd88", "deficiency caused", "caused by", "by homozygous", "homozygous or", "or compound", "compound heterozygous", "heterozygous mutations", "mutations in", "in myd88", "myd88 gene", "gene leading", "to abolished", "abolished protein", "protein production", "von bernuth", "bernuth et", "al. 2008", "2008 .", ". ar", "ar myd88", "deficiency is", "is a", "a type", "type of", "of a", "a primary", "primary immunodeficiency", "immunodeficiency characterized", "characterized by", "by greater", "greater susceptibility", "susceptibility to", "to pyogenic", "pyogenic bacteria", "bacteria such", "as invasive", "invasive pneumococcal", "pneumococcal disease", "disease manifested", "manifested in", "in infancy", "infancy and", "and early", "early childhood.", "childhood. patients", "with myd88", "deficiency show", "show delayed", "delayed or", "or weak", "weak signs", "signs of", "of inflammatory", "inflammatory responses", "picard c", "c et", "al. 2011", "2011 .

              functional", ".

              functional assessment", "assessment of", "deficiency revealed", "revealed that", "that cytokine", "cytokine responses", "responses were", "were abolished", "abolished in", "in patient", "patient derived", "derived blood", "blood cells", "cells upon", "upon stimulation", "stimulation with", "with bacterial", "bacterial flagellin", "which is", "is recognized", "recognized by", "by tlr5", ". an", "an nfkb", "nfkb luciferase", "luciferase reporter", "reporter gene", "gene assay", "assay using", "using human", "human embryonic", "embryonic kidney", "kidney 293", "cells showed", "showed that", "that myd88", "myd88 variants", "and r196c", "were compromised", "compromised in", "in the", "the ability", "ability to", "to enhance", "enhance nfkb", "nfkb activation", "yamamoto t", "t et", "al. 2014", "2014 .", "the molecular", "molecular basis", "basis for", "for the", "the observed", "observed functional", "functional effects", "reported for", "for selected", "selected mutations", "probably faulty", "faulty myddosome", "myddosome formation", "formation due", "due to", "to impaired", "impaired myd88", "myd88 oligomerization", "oligomerization and/or", "and/or interaction", "interaction with", "with irak4", "george j", "j et", "nagpal k", "k et", "2014 .

              while", ".

              while myd88", "deficiency might", "might be", "be expected", "expected to", "to perturb", "perturb myd88?irak4", "myd88?irak4 dependent", "dependent tlr7", "tlr7 and", "and tlr8", "tlr8 signaling", "signaling events", "events associated", "associated with", "the sensing", "sensing viral", "viral infections", "infections in", "the endosome", "myd88 and", "and irak4", "irak4 deficiencies", "deficiencies have", "have so", "so far", "far not", "not been", "been reported", "reported to", "to be", "be susceptible", "susceptible to", "to viral", "viral infection.", "myeloid differentiation primary", "differentiation primary response", "response myd88", "myd88 is", "is an adaptor", "an adaptor protein", "adaptor protein that", "protein that mediates", "that mediates intracellular", "mediates intracellular signaling", "intracellular signaling pathways", "signaling pathways evoked", "pathways evoked by", "evoked by all", "by all toll", "all toll like", "toll like receptors", "receptors tlrs", "except for tlr3", "tlr3 and", "and several interleukin", "several interleukin 1", "interleukin 1 receptors", "receptors il", "medzhitov r et", "r et al.", "et al. 1998", "al. 1998 .", "1998 . upon", ". upon ligand", "upon ligand binding", "binding tlrs", "hetero or", "or homodimerize and", "homodimerize and recruit", "and recruit myd88", "recruit myd88 through", "myd88 through their", "through their respective", "their respective tir", "respective tir domains.", "tir domains. then", "then myd88", "myd88 oligomerizes via", "oligomerizes via its", "via its death", "its death domain", "domain dd", "dd and", "and tir domain", "tir domain and", "domain and interacts", "and interacts with", "interacts with the", "with the interleukin", "the interleukin 1", "interleukin 1 receptor", "1 receptor associated", "receptor associated kinases", "kinases iraks", "iraks to", "to form the", "form the myddosome", "the myddosome complex", "complex myd88:irak4:irak1/2", "motshwene pg et", "pg et al.", "et al. 2009", "2009 lin", "lin sc et", "sc et al.", "et al. 2010", "al. 2010 .", "2010 . the", ". the myddosome", "myddosome complex transmits", "complex transmits the", "transmits the signal", "the signal leading", "signal leading to", "leading to activation", "to activation of", "activation of transcription", "of transcription factors", "transcription factors such", "factors such as", "such as nuclear", "as nuclear factor", "nuclear factor kappab", "kappab nfkb", "nfkb and", "and activator protein", "activator protein 1", "1 ap1", "ap1 .

              studies have", ".

              studies have identified", "have identified patients", "identified patients with", "patients with autosomal", "with autosomal recessive", "recessive ar", "ar form", "form of myd88", "of myd88 deficiency", "myd88 deficiency caused", "deficiency caused by", "caused by homozygous", "by homozygous or", "homozygous or compound", "or compound heterozygous", "compound heterozygous mutations", "heterozygous mutations in", "mutations in myd88", "in myd88 gene", "myd88 gene leading", "gene leading to", "leading to abolished", "to abolished protein", "abolished protein production", "production von", "von bernuth et", "bernuth et al.", "et al. 2008", "al. 2008 .", "2008 . ar", ". ar myd88", "ar myd88 deficiency", "myd88 deficiency is", "deficiency is a", "is a type", "a type of", "type of a", "of a primary", "a primary immunodeficiency", "primary immunodeficiency characterized", "immunodeficiency characterized by", "characterized by greater", "by greater susceptibility", "greater susceptibility to", "susceptibility to pyogenic", "to pyogenic bacteria", "pyogenic bacteria such", "bacteria such as", "such as invasive", "as invasive pneumococcal", "invasive pneumococcal disease", "pneumococcal disease manifested", "disease manifested in", "manifested in infancy", "in infancy and", "infancy and early", "and early childhood.", "early childhood. patients", "childhood. patients with", "patients with myd88", "with myd88 deficiency", "myd88 deficiency show", "deficiency show delayed", "show delayed or", "delayed or weak", "or weak signs", "weak signs of", "signs of inflammatory", "of inflammatory responses", "responses picard", "picard c et", "c et al.", "2010 picard", "et al. 2011", "al. 2011 .

              functional", "2011 .

              functional assessment", ".

              functional assessment of", "assessment of myd88", "myd88 deficiency revealed", "deficiency revealed that", "revealed that cytokine", "that cytokine responses", "cytokine responses were", "responses were abolished", "were abolished in", "abolished in patient", "in patient derived", "patient derived blood", "derived blood cells", "blood cells upon", "cells upon stimulation", "upon stimulation with", "stimulation with bacterial", "with bacterial flagellin", "flagellin which", "which is recognized", "is recognized by", "recognized by tlr5", "tlr5 von", "2008 . an", ". an nfkb", "an nfkb luciferase", "nfkb luciferase reporter", "luciferase reporter gene", "reporter gene assay", "gene assay using", "assay using human", "using human embryonic", "human embryonic kidney", "embryonic kidney 293", "293 hek293t", "hek293t cells", "cells showed that", "showed that myd88", "that myd88 variants", "variants s34y", "s34y e52del", "e52del e53x", "e53x l93p", "l93p r98c", "r98c and", "r196c were", "were compromised in", "compromised in the", "in the ability", "the ability to", "ability to enhance", "to enhance nfkb", "enhance nfkb activation", "activation yamamoto", "yamamoto t et", "t et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the molecular", "the molecular basis", "molecular basis for", "basis for the", "for the observed", "the observed functional", "observed functional effects", "effects reported", "reported for selected", "for selected mutations", "mutations probably", "probably faulty myddosome", "faulty myddosome formation", "myddosome formation due", "formation due to", "due to impaired", "to impaired myd88", "impaired myd88 oligomerization", "myd88 oligomerization and/or", "oligomerization and/or interaction", "and/or interaction with", "interaction with irak4", "irak4 george", "george j et", "j et al.", "2011 nagpal", "nagpal k et", "k et al.", "2011 yamamoto", "al. 2014 .

              while", "2014 .

              while myd88", ".

              while myd88 deficiency", "myd88 deficiency might", "deficiency might be", "might be expected", "be expected to", "expected to perturb", "to perturb myd88?irak4", "perturb myd88?irak4 dependent", "myd88?irak4 dependent tlr7", "dependent tlr7 and", "tlr7 and tlr8", "and tlr8 signaling", "tlr8 signaling events", "signaling events associated", "events associated with", "associated with the", "with the sensing", "the sensing viral", "sensing viral infections", "viral infections in", "infections in the", "in the endosome", "endosome patients", "with myd88 and", "myd88 and irak4", "and irak4 deficiencies", "irak4 deficiencies have", "deficiencies have so", "have so far", "so far not", "far not been", "not been reported", "been reported to", "reported to be", "to be susceptible", "be susceptible to", "susceptible to viral", "to viral infection.", "myeloid differentiation primary response", "primary response myd88", "myd88 is an", "is an adaptor protein", "an adaptor protein that", "adaptor protein that mediates", "protein that mediates intracellular", "that mediates intracellular signaling", "mediates intracellular signaling pathways", "intracellular signaling pathways evoked", "signaling pathways evoked by", "pathways evoked by all", "evoked by all toll", "by all toll like", "all toll like receptors", "like receptors tlrs", "tlrs except", "for tlr3 and", "tlr3 and several", "and several interleukin 1", "several interleukin 1 receptors", "1 receptors il", "receptors il 1rs", "1rs medzhitov", "medzhitov r et al.", "r et al. 1998", "et al. 1998 .", "al. 1998 . upon", "1998 . upon ligand", ". upon ligand binding", "ligand binding tlrs", "binding tlrs hetero", "tlrs hetero or", "hetero or homodimerize", "or homodimerize and recruit", "homodimerize and recruit myd88", "and recruit myd88 through", "recruit myd88 through their", "myd88 through their respective", "through their respective tir", "their respective tir domains.", "respective tir domains. then", "domains. then myd88", "then myd88 oligomerizes", "myd88 oligomerizes via its", "oligomerizes via its death", "via its death domain", "death domain dd", "dd and tir", "and tir domain and", "tir domain and interacts", "domain and interacts with", "and interacts with the", "interacts with the interleukin", "with the interleukin 1", "the interleukin 1 receptor", "interleukin 1 receptor associated", "1 receptor associated kinases", "associated kinases iraks", "iraks to form", "to form the myddosome", "form the myddosome complex", "myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene", "motshwene pg et al.", "pg et al. 2009", "al. 2009 lin", "2009 lin sc", "lin sc et al.", "sc et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the myddosome", ". the myddosome complex", "the myddosome complex transmits", "myddosome complex transmits the", "complex transmits the signal", "transmits the signal leading", "the signal leading to", "signal leading to activation", "leading to activation of", "to activation of transcription", "activation of transcription factors", "of transcription factors such", "transcription factors such as", "factors such as nuclear", "such as nuclear factor", "as nuclear factor kappab", "factor kappab nfkb", "nfkb and activator", "and activator protein 1", "protein 1 ap1", "1 ap1 .

              studies", "ap1 .

              studies have identified", ".

              studies have identified patients", "have identified patients with", "identified patients with autosomal", "patients with autosomal recessive", "autosomal recessive ar", "ar form of", "form of myd88 deficiency", "of myd88 deficiency caused", "myd88 deficiency caused by", "deficiency caused by homozygous", "caused by homozygous or", "by homozygous or compound", "homozygous or compound heterozygous", "or compound heterozygous mutations", "compound heterozygous mutations in", "heterozygous mutations in myd88", "mutations in myd88 gene", "in myd88 gene leading", "myd88 gene leading to", "gene leading to abolished", "leading to abolished protein", "to abolished protein production", "protein production von", "production von bernuth", "von bernuth et al.", "bernuth et al. 2008", "et al. 2008 .", "al. 2008 . ar", "2008 . ar myd88", ". ar myd88 deficiency", "ar myd88 deficiency is", "myd88 deficiency is a", "deficiency is a type", "is a type of", "a type of a", "type of a primary", "of a primary immunodeficiency", "a primary immunodeficiency characterized", "primary immunodeficiency characterized by", "immunodeficiency characterized by greater", "characterized by greater susceptibility", "by greater susceptibility to", "greater susceptibility to pyogenic", "susceptibility to pyogenic bacteria", "to pyogenic bacteria such", "pyogenic bacteria such as", "bacteria such as invasive", "such as invasive pneumococcal", "as invasive pneumococcal disease", "invasive pneumococcal disease manifested", "pneumococcal disease manifested in", "disease manifested in infancy", "manifested in infancy and", "in infancy and early", "infancy and early childhood.", "and early childhood. patients", "early childhood. patients with", "childhood. patients with myd88", "patients with myd88 deficiency", "with myd88 deficiency show", "myd88 deficiency show delayed", "deficiency show delayed or", "show delayed or weak", "delayed or weak signs", "or weak signs of", "weak signs of inflammatory", "signs of inflammatory responses", "inflammatory responses picard", "responses picard c", "picard c et al.", "c et al. 2010", "al. 2010 picard", "2010 picard c", "c et al. 2011", "et al. 2011 .

              functional", "al. 2011 .

              functional assessment", "2011 .

              functional assessment of", ".

              functional assessment of myd88", "assessment of myd88 deficiency", "of myd88 deficiency revealed", "myd88 deficiency revealed that", "deficiency revealed that cytokine", "revealed that cytokine responses", "that cytokine responses were", "cytokine responses were abolished", "responses were abolished in", "were abolished in patient", "abolished in patient derived", "in patient derived blood", "patient derived blood cells", "derived blood cells upon", "blood cells upon stimulation", "cells upon stimulation with", "upon stimulation with bacterial", "stimulation with bacterial flagellin", "bacterial flagellin which", "flagellin which is", "which is recognized by", "is recognized by tlr5", "by tlr5 von", "tlr5 von bernuth", "al. 2008 . an", "2008 . an nfkb", ". an nfkb luciferase", "an nfkb luciferase reporter", "nfkb luciferase reporter gene", "luciferase reporter gene assay", "reporter gene assay using", "gene assay using human", "assay using human embryonic", "using human embryonic kidney", "human embryonic kidney 293", "kidney 293 hek293t", "hek293t cells showed", "cells showed that myd88", "showed that myd88 variants", "myd88 variants s34y", "r98c and r196c", "and r196c were", "r196c were compromised", "were compromised in the", "compromised in the ability", "in the ability to", "the ability to enhance", "ability to enhance nfkb", "to enhance nfkb activation", "nfkb activation yamamoto", "activation yamamoto t", "yamamoto t et al.", "t et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the molecular", ". the molecular basis", "the molecular basis for", "molecular basis for the", "basis for the observed", "for the observed functional", "the observed functional effects", "functional effects reported", "effects reported for", "reported for selected mutations", "selected mutations probably", "mutations probably faulty", "probably faulty myddosome formation", "faulty myddosome formation due", "myddosome formation due to", "formation due to impaired", "due to impaired myd88", "to impaired myd88 oligomerization", "impaired myd88 oligomerization and/or", "myd88 oligomerization and/or interaction", "oligomerization and/or interaction with", "and/or interaction with irak4", "with irak4 george", "irak4 george j", "george j et al.", "j et al. 2011", "al. 2011 nagpal", "2011 nagpal k", "nagpal k et al.", "k et al. 2011", "al. 2011 yamamoto", "2011 yamamoto t", "et al. 2014 .

              while", "al. 2014 .

              while myd88", "2014 .

              while myd88 deficiency", ".

              while myd88 deficiency might", "myd88 deficiency might be", "deficiency might be expected", "might be expected to", "be expected to perturb", "expected to perturb myd88?irak4", "to perturb myd88?irak4 dependent", "perturb myd88?irak4 dependent tlr7", "myd88?irak4 dependent tlr7 and", "dependent tlr7 and tlr8", "tlr7 and tlr8 signaling", "and tlr8 signaling events", "tlr8 signaling events associated", "signaling events associated with", "events associated with the", "associated with the sensing", "with the sensing viral", "the sensing viral infections", "sensing viral infections in", "viral infections in the", "infections in the endosome", "the endosome patients", "endosome patients with", "patients with myd88 and", "with myd88 and irak4", "myd88 and irak4 deficiencies", "and irak4 deficiencies have", "irak4 deficiencies have so", "deficiencies have so far", "have so far not", "so far not been", "far not been reported", "not been reported to", "been reported to be", "reported to be susceptible", "to be susceptible to", "be susceptible to viral", "susceptible to viral infection.", "differentiation primary response myd88", "response myd88 is", "myd88 is an adaptor", "is an adaptor protein that", "an adaptor protein that mediates", "adaptor protein that mediates intracellular", "protein that mediates intracellular signaling", "that mediates intracellular signaling pathways", "mediates intracellular signaling pathways evoked", "intracellular signaling pathways evoked by", "signaling pathways evoked by all", "pathways evoked by all toll", "evoked by all toll like", "by all toll like receptors", "toll like receptors tlrs", "tlrs except for", "except for tlr3 and", "for tlr3 and several", "tlr3 and several interleukin", "and several interleukin 1 receptors", "interleukin 1 receptors il", "1 receptors il 1rs", "il 1rs medzhitov", "1rs medzhitov r", "medzhitov r et al. 1998", "r et al. 1998 .", "et al. 1998 . upon", "al. 1998 . upon ligand", "1998 . upon ligand binding", "upon ligand binding tlrs", "ligand binding tlrs hetero", "tlrs hetero or homodimerize", "hetero or homodimerize and", "or homodimerize and recruit myd88", "homodimerize and recruit myd88 through", "and recruit myd88 through their", "recruit myd88 through their respective", "myd88 through their respective tir", "through their respective tir domains.", "their respective tir domains. then", "tir domains. then myd88", "domains. then myd88 oligomerizes", "then myd88 oligomerizes via", "myd88 oligomerizes via its death", "oligomerizes via its death domain", "its death domain dd", "domain dd and", "dd and tir domain", "and tir domain and interacts", "tir domain and interacts with", "domain and interacts with the", "and interacts with the interleukin", "interacts with the interleukin 1", "with the interleukin 1 receptor", "the interleukin 1 receptor associated", "interleukin 1 receptor associated kinases", "receptor associated kinases iraks", "kinases iraks to", "iraks to form the", "to form the myddosome complex", "the myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene pg", "motshwene pg et al. 2009", "et al. 2009 lin", "al. 2009 lin sc", "2009 lin sc et", "lin sc et al. 2010", "sc et al. 2010 .", "et al. 2010 . the", "al. 2010 . the myddosome", "2010 . the myddosome complex", ". the myddosome complex transmits", "the myddosome complex transmits the", "myddosome complex transmits the signal", "complex transmits the signal leading", "transmits the signal leading to", "the signal leading to activation", "signal leading to activation of", "leading to activation of transcription", "to activation of transcription factors", "activation of transcription factors such", "of transcription factors such as", "transcription factors such as nuclear", "factors such as nuclear factor", "such as nuclear factor kappab", "nuclear factor kappab nfkb", "kappab nfkb and", "nfkb and activator protein", "activator protein 1 ap1", "protein 1 ap1 .

              studies", "1 ap1 .

              studies have", "ap1 .

              studies have identified patients", ".

              studies have identified patients with", "have identified patients with autosomal", "identified patients with autosomal recessive", "with autosomal recessive ar", "recessive ar form", "ar form of myd88", "form of myd88 deficiency caused", "of myd88 deficiency caused by", "myd88 deficiency caused by homozygous", "deficiency caused by homozygous or", "caused by homozygous or compound", "by homozygous or compound heterozygous", "homozygous or compound heterozygous mutations", "or compound heterozygous mutations in", "compound heterozygous mutations in myd88", "heterozygous mutations in myd88 gene", "mutations in myd88 gene leading", "in myd88 gene leading to", "myd88 gene leading to abolished", "gene leading to abolished protein", "leading to abolished protein production", "abolished protein production von", "protein production von bernuth", "production von bernuth et", "von bernuth et al. 2008", "bernuth et al. 2008 .", "et al. 2008 . ar", "al. 2008 . ar myd88", "2008 . ar myd88 deficiency", ". ar myd88 deficiency is", "ar myd88 deficiency is a", "myd88 deficiency is a type", "deficiency is a type of", "is a type of a", "a type of a primary", "type of a primary immunodeficiency", "of a primary immunodeficiency characterized", "a primary immunodeficiency characterized by", "primary immunodeficiency characterized by greater", "immunodeficiency characterized by greater susceptibility", "characterized by greater susceptibility to", "by greater susceptibility to pyogenic", "greater susceptibility to pyogenic bacteria", "susceptibility to pyogenic bacteria such", "to pyogenic bacteria such as", "pyogenic bacteria such as invasive", "bacteria such as invasive pneumococcal", "such as invasive pneumococcal disease", "as invasive pneumococcal disease manifested", "invasive pneumococcal disease manifested in", "pneumococcal disease manifested in infancy", "disease manifested in infancy and", "manifested in infancy and early", "in infancy and early childhood.", "infancy and early childhood. patients", "and early childhood. patients with", "early childhood. patients with myd88", "childhood. patients with myd88 deficiency", "patients with myd88 deficiency show", "with myd88 deficiency show delayed", "myd88 deficiency show delayed or", "deficiency show delayed or weak", "show delayed or weak signs", "delayed or weak signs of", "or weak signs of inflammatory", "weak signs of inflammatory responses", "of inflammatory responses picard", "inflammatory responses picard c", "responses picard c et", "picard c et al. 2010", "et al. 2010 picard", "al. 2010 picard c", "2010 picard c et", "picard c et al. 2011", "c et al. 2011 .

              functional", "et al. 2011 .

              functional assessment", "al. 2011 .

              functional assessment of", "2011 .

              functional assessment of myd88", ".

              functional assessment of myd88 deficiency", "assessment of myd88 deficiency revealed", "of myd88 deficiency revealed that", "myd88 deficiency revealed that cytokine", "deficiency revealed that cytokine responses", "revealed that cytokine responses were", "that cytokine responses were abolished", "cytokine responses were abolished in", "responses were abolished in patient", "were abolished in patient derived", "abolished in patient derived blood", "in patient derived blood cells", "patient derived blood cells upon", "derived blood cells upon stimulation", "blood cells upon stimulation with", "cells upon stimulation with bacterial", "upon stimulation with bacterial flagellin", "with bacterial flagellin which", "bacterial flagellin which is", "flagellin which is recognized", "which is recognized by tlr5", "recognized by tlr5 von", "by tlr5 von bernuth", "tlr5 von bernuth et", "et al. 2008 . an", "al. 2008 . an nfkb", "2008 . an nfkb luciferase", ". an nfkb luciferase reporter", "an nfkb luciferase reporter gene", "nfkb luciferase reporter gene assay", "luciferase reporter gene assay using", "reporter gene assay using human", "gene assay using human embryonic", "assay using human embryonic kidney", "using human embryonic kidney 293", "embryonic kidney 293 hek293t", "293 hek293t cells", "hek293t cells showed that", "cells showed that myd88 variants", "that myd88 variants s34y", "variants s34y e52del", "s34y e52del e53x", "e52del e53x l93p", "e53x l93p r98c", "l93p r98c and", "and r196c were compromised", "r196c were compromised in", "were compromised in the ability", "compromised in the ability to", "in the ability to enhance", "the ability to enhance nfkb", "ability to enhance nfkb activation", "enhance nfkb activation yamamoto", "nfkb activation yamamoto t", "activation yamamoto t et", "yamamoto t et al. 2014", "t et al. 2014 .", "et al. 2014 . the", "al. 2014 . the molecular", "2014 . the molecular basis", ". the molecular basis for", "the molecular basis for the", "molecular basis for the observed", "basis for the observed functional", "for the observed functional effects", "observed functional effects reported", "functional effects reported for", "effects reported for selected", "for selected mutations probably", "selected mutations probably faulty", "mutations probably faulty myddosome", "probably faulty myddosome formation due", "faulty myddosome formation due to", "myddosome formation due to impaired", "formation due to impaired myd88", "due to impaired myd88 oligomerization", "to impaired myd88 oligomerization and/or", "impaired myd88 oligomerization and/or interaction", "myd88 oligomerization and/or interaction with", "oligomerization and/or interaction with irak4", "interaction with irak4 george", "with irak4 george j", "irak4 george j et", "george j et al. 2011", "et al. 2011 nagpal", "al. 2011 nagpal k", "2011 nagpal k et", "nagpal k et al. 2011", "et al. 2011 yamamoto", "al. 2011 yamamoto t", "2011 yamamoto t et", "t et al. 2014 .

              while", "et al. 2014 .

              while myd88", "al. 2014 .

              while myd88 deficiency", "2014 .

              while myd88 deficiency might", ".

              while myd88 deficiency might be", "myd88 deficiency might be expected", "deficiency might be expected to", "might be expected to perturb", "be expected to perturb myd88?irak4", "expected to perturb myd88?irak4 dependent", "to perturb myd88?irak4 dependent tlr7", "perturb myd88?irak4 dependent tlr7 and", "myd88?irak4 dependent tlr7 and tlr8", "dependent tlr7 and tlr8 signaling", "tlr7 and tlr8 signaling events", "and tlr8 signaling events associated", "tlr8 signaling events associated with", "signaling events associated with the", "events associated with the sensing", "associated with the sensing viral", "with the sensing viral infections", "the sensing viral infections in", "sensing viral infections in the", "viral infections in the endosome", "in the endosome patients", "the endosome patients with", "endosome patients with myd88", "patients with myd88 and irak4", "with myd88 and irak4 deficiencies", "myd88 and irak4 deficiencies have", "and irak4 deficiencies have so", "irak4 deficiencies have so far", "deficiencies have so far not", "have so far not been", "so far not been reported", "far not been reported to", "not been reported to be", "been reported to be susceptible", "reported to be susceptible to", "to be susceptible to viral", "be susceptible to viral infection." ] }, { "record_id": "GLY_000594_1_1017", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5603037", "r hsa", "hsa 5603037", "r hsa 5603037" ] }, { "record_id": "GLY_000594_1_1017", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak4 deficiency", "deficiency tlr5", "irak4 deficiency tlr5", "toll like", "like receptor", "receptor 5", "specifically recognizes", "recognizes bacterial", "bacterial infection", "infection through", "through binding", "binding of", "of flagellin", "flagellin from", "from pathogenic", "pathogenic bacteria.", "bacteria. upon", "upon ligand", "ligand binding", "tlr5 dimers", "dimers recruit", "recruit myd88", "myd88 through", "through their", "their tir", "tir domains.", "domains. then", "myd88 oligomerizes", "oligomerizes via", "via its", "its death", "death domain", "and tir", "tir domain", "domain and", "and interacts", "interacts with", "with the", "the interleukin", "interleukin 1", "1 receptor", "receptor associated", "associated kinases", "to form", "form the", "the myddosome", "myddosome complex", "motshwene pg", "pg et", "et al.", "al. 2009", "lin sc", "sc et", "al. 2010", "2010 .", ". the", "complex transmits", "transmits the", "the signal", "signal leading", "leading to", "to activation", "activation of", "of transcription", "transcription factors", "factors such", "such as", "as nuclear", "nuclear factor", "factor kappab", "and activator", "activator protein", "protein 1", "ap1 .", ". studies", "studies have", "have identified", "identified patients", "patients with", "with autosomal", "autosomal recessive", "form of", "of irak4", "a health", "health condition", "condition with", "with clinical", "clinical manifestation", "manifestation in", "in infancy", "infancy or", "or early", "early childhood", "that predisposes", "predisposes affected", "affected patients", "patients to", "to recurrent", "recurrent pyogenic", "pyogenic bacterial", "streptococcus pneumoniae", "pneumoniae and", "and staphylococcus", "staphylococcus aureus", "picard c", "c et", "al. 2003", "ku cl", "cl et", "al. 2007", "al. 2011", "2011 .", ". leukocytes", "leukocytes derived", "derived from", "from irak4", "irak4 deficient", "deficient patients", "patients display", "display a", "a lack", "lack of", "of production", "production of", "of inflammatory", "inflammatory cytokines", "cytokines such", "as tnf", "tnf alpha", "il 6", "6 and", "and il", "il 1beta", "1beta or", "or a", "of cd62", "cd62 ligand", "shedding from", "from granulocytes", "granulocytes following", "following activation", "activation with", "with flagellin", "the tlr5", "tlr5 agonist", "mcdonald dr", "dr et", "al. 2006", "2007 .", ". patients", "with ar", "ar irak4", "deficiency were", "were found", "found to", "to bear", "bear homozygous", "homozygous or", "or compound", "compound heterozygous", "heterozygous mutations", "mutations in", "in the", "the irak4", "irak4 gene", "2006 .", ". here", "here we", "we describe", "describe selective", "selective mutations", "that have", "have been", "been functionally", "functionally characterized.", "characterized. cell", "cell based", "based assays", "assays as", "as well", "well as", "as in", "in vitro", "vitro protein", "protein interaction", "interaction analyses", "analyses with", "with irak4", "irak4 variants", "variants showed", "showed that", "that the", "the loss", "loss of", "of function", "function of", "of defective", "defective irak4", "irak4 can", "can be", "be caused", "caused by", "by either", "either an", "an abolished", "abolished protein", "protein production", "production as", "as a", "a result", "result of", "of nonsense", "nonsense mutations", "e.g. q293*", "q293* and", "and e402*", "or an", "an impaired", "impaired interaction", "interaction with", "with myd88", "myd88 due", "due to", "to missense", "missense mutations", "yamamoto t", "t et", "al. 2014", "2014 .

              irak4", ".

              irak4 mediates", "mediates immune", "immune responses", "responses downstream", "downstream of", "of all", "all tlrs", "tlrs except", "except for", "for tlr3.", "tlr3. besides", "besides defective", "defective tlr5", "tlr5 signaling", "the reactome", "reactome module", "module describes", "describes the", "the impact", "impact of", "of functional", "functional deficiency", "deficiency of", "irak4 on", "on tlr2/4", "tlr2/4 signaling", "signaling pathways.", "pathways. we", "we did", "did not", "not include", "include defective", "defective tlr7", "tlr8 and", "and tlr9", "tlr9 signaling", "signaling events", "which are", "are stimulated", "stimulated by", "by nucleic", "nucleic acids", "acids upon", "upon viral", "viral infections", "although studies", "studies using", "using patients", "patients derived", "derived blood", "blood cells", "cells have", "have showed", "showed abolished", "abolished cytokines", "cytokines production", "production by", "by peripheral", "peripheral blood", "blood mononuclear", "mononuclear cells", "and lack", "granulocytes in", "in response", "response to", "to tlr7", "tlr7 9", "9 agonists", "i.e. 3m", "3m 13", "3m 2", "tlr7 and", "and 8", "and cpg", "von bernuth", "bernuth h", "h et", ". in", "in addition", "addition to", "to tlr", "tlr nfkb", "nfkb signaling", "signaling axis", "axis the", "the endosomic", "endosomic tlr7", "9 activate", "activate ifn", "ifn alpha/beta", "alpha/beta and", "and ifn", "ifn gamma", "gamma responses", "which have", "been also", "also impaired", "impaired in", "in irak4", "deficient pbmc", "yang k", "k et", "al. 2005", "2005 .", ". however", "gamma production", "production in", "to 9", "9 of", "of 11", "11 viruses", "viruses tested", "tested was", "was normal", "normal or", "or weakly", "weakly affected", "affected in", "in irak", "irak 4", "4 deficient", "deficient blood", "suggesting that", "that irak", "patients may", "may control", "control viral", "infections by", "by tlr7", "9 independent", "independent production", "of ifns", ". so", "so it", "it is", "is not", "not yet", "yet possible", "possible to", "to annotate", "annotate a", "a definitive", "definitive molecular", "molecular pathway", "pathway between", "between irak", "4 deficiency", "deficiency and", "and changes", "changes in", "in tlr7", "9 signaling.", "toll like receptor", "like receptor 5", "5 tlr5", "tlr5 specifically", "specifically recognizes bacterial", "recognizes bacterial infection", "bacterial infection through", "infection through binding", "through binding of", "binding of flagellin", "of flagellin from", "flagellin from pathogenic", "from pathogenic bacteria.", "pathogenic bacteria. upon", "bacteria. upon ligand", "upon ligand binding", "binding tlr5", "tlr5 dimers recruit", "dimers recruit myd88", "recruit myd88 through", "myd88 through their", "through their tir", "their tir domains.", "tir domains. then", "then myd88", "myd88 oligomerizes via", "oligomerizes via its", "via its death", "its death domain", "domain dd", "dd and", "and tir domain", "tir domain and", "domain and interacts", "and interacts with", "interacts with the", "with the interleukin", "the interleukin 1", "interleukin 1 receptor", "1 receptor associated", "receptor associated kinases", "kinases iraks", "iraks to", "to form the", "form the myddosome", "the myddosome complex", "complex myd88:irak4:irak1/2", "motshwene pg et", "pg et al.", "et al. 2009", "2009 lin", "lin sc et", "sc et al.", "et al. 2010", "al. 2010 .", "2010 . the", ". the myddosome", "myddosome complex transmits", "complex transmits the", "transmits the signal", "the signal leading", "signal leading to", "leading to activation", "to activation of", "activation of transcription", "of transcription factors", "transcription factors such", "factors such as", "such as nuclear", "as nuclear factor", "nuclear factor kappab", "kappab nfkb", "nfkb and", "and activator protein", "activator protein 1", "1 ap1", "ap1 . studies", ". studies have", "studies have identified", "have identified patients", "identified patients with", "patients with autosomal", "with autosomal recessive", "recessive ar", "ar form", "form of irak4", "of irak4 deficiency", "deficiency a", "a health condition", "health condition with", "condition with clinical", "with clinical manifestation", "clinical manifestation in", "manifestation in infancy", "in infancy or", "infancy or early", "or early childhood", "childhood that", "that predisposes affected", "predisposes affected patients", "affected patients to", "patients to recurrent", "to recurrent pyogenic", "recurrent pyogenic bacterial", "pyogenic bacterial infection", "infection e.g.", "e.g. streptococcus", "streptococcus pneumoniae and", "pneumoniae and staphylococcus", "and staphylococcus aureus", "picard c et", "c et al.", "et al. 2003", "2003 ku", "ku cl et", "cl et al.", "et al. 2007", "2007 picard", "2010 picard", "et al. 2011", "al. 2011 .", "2011 . leukocytes", ". leukocytes derived", "leukocytes derived from", "derived from irak4", "from irak4 deficient", "irak4 deficient patients", "deficient patients display", "patients display a", "display a lack", "a lack of", "lack of production", "of production of", "production of inflammatory", "of inflammatory cytokines", "inflammatory cytokines such", "cytokines such as", "such as tnf", "as tnf alpha", "alpha il", "il 6 and", "6 and il", "and il 1beta", "il 1beta or", "1beta or a", "or a lack", "lack of cd62", "of cd62 ligand", "ligand cd62l", "cd62l shedding", "shedding from granulocytes", "from granulocytes following", "granulocytes following activation", "following activation with", "activation with flagellin", "flagellin the", "the tlr5 agonist", "agonist picard", "2003 mcdonald", "mcdonald dr et", "dr et al.", "et al. 2006", "2006 ku", "al. 2007 .", "2007 . patients", ". patients with", "patients with ar", "with ar irak4", "ar irak4 deficiency", "irak4 deficiency were", "deficiency were found", "were found to", "found to bear", "to bear homozygous", "bear homozygous or", "homozygous or compound", "or compound heterozygous", "compound heterozygous mutations", "heterozygous mutations in", "mutations in the", "in the irak4", "the irak4 gene", "gene picard", "2007 mcdonald", "al. 2006 .", "2006 . here", ". here we", "here we describe", "we describe selective", "describe selective mutations", "mutations that", "that have been", "have been functionally", "been functionally characterized.", "functionally characterized. cell", "characterized. cell based", "cell based assays", "based assays as", "assays as well", "as well as", "well as in", "as in vitro", "in vitro protein", "vitro protein interaction", "protein interaction analyses", "interaction analyses with", "analyses with irak4", "with irak4 variants", "irak4 variants showed", "variants showed that", "showed that the", "that the loss", "the loss of", "loss of function", "of function of", "function of defective", "of defective irak4", "defective irak4 can", "irak4 can be", "can be caused", "be caused by", "caused by either", "by either an", "either an abolished", "an abolished protein", "abolished protein production", "protein production as", "production as a", "as a result", "a result of", "result of nonsense", "of nonsense mutations", "mutations e.g.", "e.g. q293* and", "q293* and e402*", "or an impaired", "an impaired interaction", "impaired interaction with", "interaction with myd88", "with myd88 due", "myd88 due to", "due to missense", "to missense mutations", "e.g. r12c", "2007 yamamoto", "yamamoto t et", "t et al.", "et al. 2014", "al. 2014 .

              irak4", "2014 .

              irak4 mediates", ".

              irak4 mediates immune", "mediates immune responses", "immune responses downstream", "responses downstream of", "downstream of all", "of all tlrs", "all tlrs except", "tlrs except for", "except for tlr3.", "for tlr3. besides", "tlr3. besides defective", "besides defective tlr5", "defective tlr5 signaling", "signaling the", "the reactome module", "reactome module describes", "module describes the", "describes the impact", "the impact of", "impact of functional", "of functional deficiency", "functional deficiency of", "deficiency of irak4", "of irak4 on", "irak4 on tlr2/4", "on tlr2/4 signaling", "tlr2/4 signaling pathways.", "signaling pathways. we", "pathways. we did", "we did not", "did not include", "not include defective", "include defective tlr7", "tlr7 tlr8", "tlr8 and tlr9", "and tlr9 signaling", "tlr9 signaling events", "events which", "which are stimulated", "are stimulated by", "stimulated by nucleic", "by nucleic acids", "nucleic acids upon", "acids upon viral", "upon viral infections", "infections although", "although studies using", "studies using patients", "using patients derived", "patients derived blood", "derived blood cells", "blood cells have", "cells have showed", "have showed abolished", "showed abolished cytokines", "abolished cytokines production", "cytokines production by", "production by peripheral", "by peripheral blood", "peripheral blood mononuclear", "blood mononuclear cells", "cells pbmcs", "pbmcs and", "and lack of", "from granulocytes in", "granulocytes in response", "in response to", "response to tlr7", "to tlr7 9", "tlr7 9 agonists", "agonists i.e.", "i.e. 3m 13", "13 tlr7", "2 tlr8", "r848 tlr7", "tlr7 and 8", "8 and", "cpg tlr9", "2006 von", "von bernuth h", "bernuth h et", "h et al.", "2007 . in", ". in addition", "in addition to", "addition to tlr", "to tlr nfkb", "tlr nfkb signaling", "nfkb signaling axis", "signaling axis the", "axis the endosomic", "the endosomic tlr7", "endosomic tlr7 9", "tlr7 9 activate", "9 activate ifn", "activate ifn alpha/beta", "ifn alpha/beta and", "alpha/beta and ifn", "and ifn gamma", "ifn gamma responses", "responses which", "which have been", "have been also", "been also impaired", "also impaired in", "impaired in irak4", "in irak4 deficient", "irak4 deficient pbmc", "pbmc yang", "yang k et", "k et al.", "et al. 2005", "al. 2005 .", "2005 . however", "however ifn", "ifn gamma production", "gamma production in", "production in response", "response to 9", "to 9 of", "9 of 11", "of 11 viruses", "11 viruses tested", "viruses tested was", "tested was normal", "was normal or", "normal or weakly", "or weakly affected", "weakly affected in", "affected in irak", "in irak 4", "irak 4 deficient", "4 deficient blood", "deficient blood cells", "cells suggesting", "suggesting that irak", "that irak 4", "4 deficient patients", "deficient patients may", "patients may control", "may control viral", "control viral infections", "viral infections by", "infections by tlr7", "by tlr7 9", "tlr7 9 independent", "9 independent production", "independent production of", "production of ifns", "ifns yang", "2005 . so", ". so it", "so it is", "it is not", "is not yet", "not yet possible", "yet possible to", "possible to annotate", "to annotate a", "annotate a definitive", "a definitive molecular", "definitive molecular pathway", "molecular pathway between", "pathway between irak", "between irak 4", "irak 4 deficiency", "4 deficiency and", "deficiency and changes", "and changes in", "changes in tlr7", "in tlr7 9", "tlr7 9 signaling.", "toll like receptor 5", "receptor 5 tlr5", "tlr5 specifically recognizes", "specifically recognizes bacterial infection", "recognizes bacterial infection through", "bacterial infection through binding", "infection through binding of", "through binding of flagellin", "binding of flagellin from", "of flagellin from pathogenic", "flagellin from pathogenic bacteria.", "from pathogenic bacteria. upon", "pathogenic bacteria. upon ligand", "bacteria. upon ligand binding", "ligand binding tlr5", "binding tlr5 dimers", "tlr5 dimers recruit myd88", "dimers recruit myd88 through", "recruit myd88 through their", "myd88 through their tir", "through their tir domains.", "their tir domains. then", "domains. then myd88", "then myd88 oligomerizes", "myd88 oligomerizes via its", "oligomerizes via its death", "via its death domain", "death domain dd", "dd and tir", "and tir domain and", "tir domain and interacts", "domain and interacts with", "and interacts with the", "interacts with the interleukin", "with the interleukin 1", "the interleukin 1 receptor", "interleukin 1 receptor associated", "1 receptor associated kinases", "associated kinases iraks", "iraks to form", "to form the myddosome", "form the myddosome complex", "myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene", "motshwene pg et al.", "pg et al. 2009", "al. 2009 lin", "2009 lin sc", "lin sc et al.", "sc et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the myddosome", ". the myddosome complex", "the myddosome complex transmits", "myddosome complex transmits the", "complex transmits the signal", "transmits the signal leading", "the signal leading to", "signal leading to activation", "leading to activation of", "to activation of transcription", "activation of transcription factors", "of transcription factors such", "transcription factors such as", "factors such as nuclear", "such as nuclear factor", "as nuclear factor kappab", "factor kappab nfkb", "nfkb and activator", "and activator protein 1", "protein 1 ap1", "1 ap1 .", "ap1 . studies have", ". studies have identified", "studies have identified patients", "have identified patients with", "identified patients with autosomal", "patients with autosomal recessive", "autosomal recessive ar", "ar form of", "form of irak4 deficiency", "irak4 deficiency a", "deficiency a health", "a health condition with", "health condition with clinical", "condition with clinical manifestation", "with clinical manifestation in", "clinical manifestation in infancy", "manifestation in infancy or", "in infancy or early", "infancy or early childhood", "early childhood that", "childhood that predisposes", "that predisposes affected patients", "predisposes affected patients to", "affected patients to recurrent", "patients to recurrent pyogenic", "to recurrent pyogenic bacterial", "recurrent pyogenic bacterial infection", "bacterial infection e.g.", "e.g. streptococcus pneumoniae", "streptococcus pneumoniae and staphylococcus", "pneumoniae and staphylococcus aureus", "aureus picard", "picard c et al.", "c et al. 2003", "al. 2003 ku", "2003 ku cl", "ku cl et al.", "cl et al. 2007", "al. 2007 picard", "2007 picard c", "c et al. 2010", "al. 2010 picard", "2010 picard c", "c et al. 2011", "et al. 2011 .", "al. 2011 . leukocytes", "2011 . leukocytes derived", ". leukocytes derived from", "leukocytes derived from irak4", "derived from irak4 deficient", "from irak4 deficient patients", "irak4 deficient patients display", "deficient patients display a", "patients display a lack", "display a lack of", "a lack of production", "lack of production of", "of production of inflammatory", "production of inflammatory cytokines", "of inflammatory cytokines such", "inflammatory cytokines such as", "cytokines such as tnf", "such as tnf alpha", "tnf alpha il", "alpha il 6", "il 6 and il", "6 and il 1beta", "and il 1beta or", "il 1beta or a", "1beta or a lack", "or a lack of", "a lack of cd62", "lack of cd62 ligand", "cd62 ligand cd62l", "cd62l shedding from", "shedding from granulocytes following", "from granulocytes following activation", "granulocytes following activation with", "following activation with flagellin", "with flagellin the", "flagellin the tlr5", "tlr5 agonist picard", "agonist picard c", "al. 2003 mcdonald", "2003 mcdonald dr", "mcdonald dr et al.", "dr et al. 2006", "al. 2006 ku", "2006 ku cl", "et al. 2007 .", "al. 2007 . patients", "2007 . patients with", ". patients with ar", "patients with ar irak4", "with ar irak4 deficiency", "ar irak4 deficiency were", "irak4 deficiency were found", "deficiency were found to", "were found to bear", "found to bear homozygous", "to bear homozygous or", "bear homozygous or compound", "homozygous or compound heterozygous", "or compound heterozygous mutations", "compound heterozygous mutations in", "heterozygous mutations in the", "mutations in the irak4", "in the irak4 gene", "irak4 gene picard", "gene picard c", "al. 2007 mcdonald", "2007 mcdonald dr", "et al. 2006 .", "al. 2006 . here", "2006 . here we", ". here we describe", "here we describe selective", "we describe selective mutations", "selective mutations that", "mutations that have", "that have been functionally", "have been functionally characterized.", "been functionally characterized. cell", "functionally characterized. cell based", "characterized. cell based assays", "cell based assays as", "based assays as well", "assays as well as", "as well as in", "well as in vitro", "as in vitro protein", "in vitro protein interaction", "vitro protein interaction analyses", "protein interaction analyses with", "interaction analyses with irak4", "analyses with irak4 variants", "with irak4 variants showed", "irak4 variants showed that", "variants showed that the", "showed that the loss", "that the loss of", "the loss of function", "loss of function of", "of function of defective", "function of defective irak4", "of defective irak4 can", "defective irak4 can be", "irak4 can be caused", "can be caused by", "be caused by either", "caused by either an", "by either an abolished", "either an abolished protein", "an abolished protein production", "abolished protein production as", "protein production as a", "production as a result", "as a result of", "a result of nonsense", "result of nonsense mutations", "nonsense mutations e.g.", "mutations e.g. q293*", "e.g. q293* and e402*", "e402* or", "or an impaired interaction", "an impaired interaction with", "impaired interaction with myd88", "interaction with myd88 due", "with myd88 due to", "myd88 due to missense", "due to missense mutations", "missense mutations e.g.", "r12c ku", "al. 2007 yamamoto", "2007 yamamoto t", "yamamoto t et al.", "t et al. 2014", "et al. 2014 .

              irak4", "al. 2014 .

              irak4 mediates", "2014 .

              irak4 mediates immune", ".

              irak4 mediates immune responses", "mediates immune responses downstream", "immune responses downstream of", "responses downstream of all", "downstream of all tlrs", "of all tlrs except", "all tlrs except for", "tlrs except for tlr3.", "except for tlr3. besides", "for tlr3. besides defective", "tlr3. besides defective tlr5", "besides defective tlr5 signaling", "tlr5 signaling the", "signaling the reactome", "the reactome module describes", "reactome module describes the", "module describes the impact", "describes the impact of", "the impact of functional", "impact of functional deficiency", "of functional deficiency of", "functional deficiency of irak4", "deficiency of irak4 on", "of irak4 on tlr2/4", "irak4 on tlr2/4 signaling", "on tlr2/4 signaling pathways.", "tlr2/4 signaling pathways. we", "signaling pathways. we did", "pathways. we did not", "we did not include", "did not include defective", "not include defective tlr7", "defective tlr7 tlr8", "tlr7 tlr8 and", "tlr8 and tlr9 signaling", "and tlr9 signaling events", "signaling events which", "events which are", "which are stimulated by", "are stimulated by nucleic", "stimulated by nucleic acids", "by nucleic acids upon", "nucleic acids upon viral", "acids upon viral infections", "viral infections although", "infections although studies", "although studies using patients", "studies using patients derived", "using patients derived blood", "patients derived blood cells", "derived blood cells have", "blood cells have showed", "cells have showed abolished", "have showed abolished cytokines", "showed abolished cytokines production", "abolished cytokines production by", "cytokines production by peripheral", "production by peripheral blood", "by peripheral blood mononuclear", "peripheral blood mononuclear cells", "mononuclear cells pbmcs", "pbmcs and lack", "and lack of cd62", "shedding from granulocytes in", "from granulocytes in response", "granulocytes in response to", "in response to tlr7", "response to tlr7 9", "to tlr7 9 agonists", "9 agonists i.e.", "agonists i.e. 3m", "3m 13 tlr7", "tlr7 3m", "3m 2 tlr8", "tlr8 r848", "r848 tlr7 and", "and 8 and", "8 and cpg", "and cpg tlr9", "tlr9 mcdonald", "al. 2006 von", "2006 von bernuth", "von bernuth h et", "bernuth h et al.", "h et al. 2006", "al. 2007 . in", "2007 . in addition", ". in addition to", "in addition to tlr", "addition to tlr nfkb", "to tlr nfkb signaling", "tlr nfkb signaling axis", "nfkb signaling axis the", "signaling axis the endosomic", "axis the endosomic tlr7", "the endosomic tlr7 9", "endosomic tlr7 9 activate", "tlr7 9 activate ifn", "9 activate ifn alpha/beta", "activate ifn alpha/beta and", "ifn alpha/beta and ifn", "alpha/beta and ifn gamma", "and ifn gamma responses", "gamma responses which", "responses which have", "which have been also", "have been also impaired", "been also impaired in", "also impaired in irak4", "impaired in irak4 deficient", "in irak4 deficient pbmc", "deficient pbmc yang", "pbmc yang k", "yang k et al.", "k et al. 2005", "et al. 2005 .", "al. 2005 . however", ". however ifn", "however ifn alpha/beta", "and ifn gamma production", "ifn gamma production in", "gamma production in response", "production in response to", "in response to 9", "response to 9 of", "to 9 of 11", "9 of 11 viruses", "of 11 viruses tested", "11 viruses tested was", "viruses tested was normal", "tested was normal or", "was normal or weakly", "normal or weakly affected", "or weakly affected in", "weakly affected in irak", "affected in irak 4", "in irak 4 deficient", "irak 4 deficient blood", "4 deficient blood cells", "blood cells suggesting", "cells suggesting that", "suggesting that irak 4", "that irak 4 deficient", "irak 4 deficient patients", "4 deficient patients may", "deficient patients may control", "patients may control viral", "may control viral infections", "control viral infections by", "viral infections by tlr7", "infections by tlr7 9", "by tlr7 9 independent", "tlr7 9 independent production", "9 independent production of", "independent production of ifns", "of ifns yang", "ifns yang k", "al. 2005 . so", "2005 . so it", ". so it is", "so it is not", "it is not yet", "is not yet possible", "not yet possible to", "yet possible to annotate", "possible to annotate a", "to annotate a definitive", "annotate a definitive molecular", "a definitive molecular pathway", "definitive molecular pathway between", "molecular pathway between irak", "pathway between irak 4", "between irak 4 deficiency", "irak 4 deficiency and", "4 deficiency and changes", "deficiency and changes in", "and changes in tlr7", "changes in tlr7 9", "in tlr7 9 signaling.", "like receptor 5 tlr5", "5 tlr5 specifically", "tlr5 specifically recognizes bacterial", "specifically recognizes bacterial infection through", "recognizes bacterial infection through binding", "bacterial infection through binding of", "infection through binding of flagellin", "through binding of flagellin from", "binding of flagellin from pathogenic", "of flagellin from pathogenic bacteria.", "flagellin from pathogenic bacteria. upon", "from pathogenic bacteria. upon ligand", "pathogenic bacteria. upon ligand binding", "upon ligand binding tlr5", "ligand binding tlr5 dimers", "binding tlr5 dimers recruit", "tlr5 dimers recruit myd88 through", "dimers recruit myd88 through their", "recruit myd88 through their tir", "myd88 through their tir domains.", "through their tir domains. then", "tir domains. then myd88", "domains. then myd88 oligomerizes", "then myd88 oligomerizes via", "myd88 oligomerizes via its death", "oligomerizes via its death domain", "its death domain dd", "domain dd and", "dd and tir domain", "and tir domain and interacts", "tir domain and interacts with", "domain and interacts with the", "and interacts with the interleukin", "interacts with the interleukin 1", "with the interleukin 1 receptor", "the interleukin 1 receptor associated", "interleukin 1 receptor associated kinases", "receptor associated kinases iraks", "kinases iraks to", "iraks to form the", "to form the myddosome complex", "the myddosome complex myd88:irak4:irak1/2", "myd88:irak4:irak1/2 motshwene pg", "motshwene pg et al. 2009", "et al. 2009 lin", "al. 2009 lin sc", "2009 lin sc et", "lin sc et al. 2010", "sc et al. 2010 .", "et al. 2010 . the", "al. 2010 . the myddosome", "2010 . the myddosome complex", ". the myddosome complex transmits", "the myddosome complex transmits the", "myddosome complex transmits the signal", "complex transmits the signal leading", "transmits the signal leading to", "the signal leading to activation", "signal leading to activation of", "leading to activation of transcription", "to activation of transcription factors", "activation of transcription factors such", "of transcription factors such as", "transcription factors such as nuclear", "factors such as nuclear factor", "such as nuclear factor kappab", "nuclear factor kappab nfkb", "kappab nfkb and", "nfkb and activator protein", "activator protein 1 ap1", "protein 1 ap1 .", "1 ap1 . studies", "ap1 . studies have identified", ". studies have identified patients", "studies have identified patients with", "have identified patients with autosomal", "identified patients with autosomal recessive", "with autosomal recessive ar", "recessive ar form", "ar form of irak4", "of irak4 deficiency a", "irak4 deficiency a health", "deficiency a health condition", "a health condition with clinical", "health condition with clinical manifestation", "condition with clinical manifestation in", "with clinical manifestation in infancy", "clinical manifestation in infancy or", "manifestation in infancy or early", "in infancy or early childhood", "or early childhood that", "early childhood that predisposes", "childhood that predisposes affected", "that predisposes affected patients to", "predisposes affected patients to recurrent", "affected patients to recurrent pyogenic", "patients to recurrent pyogenic bacterial", "to recurrent pyogenic bacterial infection", "pyogenic bacterial infection e.g.", "infection e.g. streptococcus", "e.g. streptococcus pneumoniae and", "streptococcus pneumoniae and staphylococcus aureus", "staphylococcus aureus picard", "aureus picard c", "picard c et al. 2003", "et al. 2003 ku", "al. 2003 ku cl", "2003 ku cl et", "ku cl et al. 2007", "et al. 2007 picard", "al. 2007 picard c", "2007 picard c et", "picard c et al. 2010", "et al. 2010 picard", "al. 2010 picard c", "2010 picard c et", "picard c et al. 2011", "c et al. 2011 .", "et al. 2011 . leukocytes", "al. 2011 . leukocytes derived", "2011 . leukocytes derived from", ". leukocytes derived from irak4", "leukocytes derived from irak4 deficient", "derived from irak4 deficient patients", "from irak4 deficient patients display", "irak4 deficient patients display a", "deficient patients display a lack", "patients display a lack of", "display a lack of production", "a lack of production of", "lack of production of inflammatory", "of production of inflammatory cytokines", "production of inflammatory cytokines such", "of inflammatory cytokines such as", "inflammatory cytokines such as tnf", "cytokines such as tnf alpha", "as tnf alpha il", "tnf alpha il 6", "alpha il 6 and", "il 6 and il 1beta", "6 and il 1beta or", "and il 1beta or a", "il 1beta or a lack", "1beta or a lack of", "or a lack of cd62", "a lack of cd62 ligand", "of cd62 ligand cd62l", "ligand cd62l shedding", "cd62l shedding from granulocytes", "shedding from granulocytes following activation", "from granulocytes following activation with", "granulocytes following activation with flagellin", "activation with flagellin the", "with flagellin the tlr5", "flagellin the tlr5 agonist", "the tlr5 agonist picard", "tlr5 agonist picard c", "agonist picard c et", "et al. 2003 mcdonald", "al. 2003 mcdonald dr", "2003 mcdonald dr et", "mcdonald dr et al. 2006", "et al. 2006 ku", "al. 2006 ku cl", "2006 ku cl et", "cl et al. 2007 .", "et al. 2007 . patients", "al. 2007 . patients with", "2007 . patients with ar", ". patients with ar irak4", "patients with ar irak4 deficiency", "with ar irak4 deficiency were", "ar irak4 deficiency were found", "irak4 deficiency were found to", "deficiency were found to bear", "were found to bear homozygous", "found to bear homozygous or", "to bear homozygous or compound", "bear homozygous or compound heterozygous", "homozygous or compound heterozygous mutations", "or compound heterozygous mutations in", "compound heterozygous mutations in the", "heterozygous mutations in the irak4", "mutations in the irak4 gene", "the irak4 gene picard", "irak4 gene picard c", "gene picard c et", "et al. 2007 mcdonald", "al. 2007 mcdonald dr", "2007 mcdonald dr et", "dr et al. 2006 .", "et al. 2006 . here", "al. 2006 . here we", "2006 . here we describe", ". here we describe selective", "here we describe selective mutations", "describe selective mutations that", "selective mutations that have", "mutations that have been", "that have been functionally characterized.", "have been functionally characterized. cell", "been functionally characterized. cell based", "functionally characterized. cell based assays", "characterized. cell based assays as", "cell based assays as well", "based assays as well as", "assays as well as in", "as well as in vitro", "well as in vitro protein", "as in vitro protein interaction", "in vitro protein interaction analyses", "vitro protein interaction analyses with", "protein interaction analyses with irak4", "interaction analyses with irak4 variants", "analyses with irak4 variants showed", "with irak4 variants showed that", "irak4 variants showed that the", "variants showed that the loss", "showed that the loss of", "that the loss of function", "the loss of function of", "loss of function of defective", "of function of defective irak4", "function of defective irak4 can", "of defective irak4 can be", "defective irak4 can be caused", "irak4 can be caused by", "can be caused by either", "be caused by either an", "caused by either an abolished", "by either an abolished protein", "either an abolished protein production", "an abolished protein production as", "abolished protein production as a", "protein production as a result", "production as a result of", "as a result of nonsense", "a result of nonsense mutations", "of nonsense mutations e.g.", "nonsense mutations e.g. q293*", "mutations e.g. q293* and", "and e402* or", "e402* or an", "or an impaired interaction with", "an impaired interaction with myd88", "impaired interaction with myd88 due", "interaction with myd88 due to", "with myd88 due to missense", "myd88 due to missense mutations", "to missense mutations e.g.", "mutations e.g. r12c", "r12c ku cl", "et al. 2007 yamamoto", "al. 2007 yamamoto t", "2007 yamamoto t et", "yamamoto t et al. 2014", "t et al. 2014 .

              irak4", "et al. 2014 .

              irak4 mediates", "al. 2014 .

              irak4 mediates immune", "2014 .

              irak4 mediates immune responses", ".

              irak4 mediates immune responses downstream", "mediates immune responses downstream of", "immune responses downstream of all", "responses downstream of all tlrs", "downstream of all tlrs except", "of all tlrs except for", "all tlrs except for tlr3.", "tlrs except for tlr3. besides", "except for tlr3. besides defective", "for tlr3. besides defective tlr5", "tlr3. besides defective tlr5 signaling", "defective tlr5 signaling the", "tlr5 signaling the reactome", "signaling the reactome module", "the reactome module describes the", "reactome module describes the impact", "module describes the impact of", "describes the impact of functional", "the impact of functional deficiency", "impact of functional deficiency of", "of functional deficiency of irak4", "functional deficiency of irak4 on", "deficiency of irak4 on tlr2/4", "of irak4 on tlr2/4 signaling", "irak4 on tlr2/4 signaling pathways.", "on tlr2/4 signaling pathways. we", "tlr2/4 signaling pathways. we did", "signaling pathways. we did not", "pathways. we did not include", "we did not include defective", "did not include defective tlr7", "include defective tlr7 tlr8", "defective tlr7 tlr8 and", "tlr7 tlr8 and tlr9", "tlr8 and tlr9 signaling events", "tlr9 signaling events which", "signaling events which are", "events which are stimulated", "which are stimulated by nucleic", "are stimulated by nucleic acids", "stimulated by nucleic acids upon", "by nucleic acids upon viral", "nucleic acids upon viral infections", "upon viral infections although", "viral infections although studies", "infections although studies using", "although studies using patients derived", "studies using patients derived blood", "using patients derived blood cells", "patients derived blood cells have", "derived blood cells have showed", "blood cells have showed abolished", "cells have showed abolished cytokines", "have showed abolished cytokines production", "showed abolished cytokines production by", "abolished cytokines production by peripheral", "cytokines production by peripheral blood", "production by peripheral blood mononuclear", "by peripheral blood mononuclear cells", "blood mononuclear cells pbmcs", "cells pbmcs and", "pbmcs and lack of", "and lack of cd62 ligand", "shedding from granulocytes in response", "from granulocytes in response to", "granulocytes in response to tlr7", "in response to tlr7 9", "response to tlr7 9 agonists", "tlr7 9 agonists i.e.", "9 agonists i.e. 3m", "agonists i.e. 3m 13", "i.e. 3m 13 tlr7", "tlr7 3m 2", "r848 tlr7 and 8", "tlr7 and 8 and", "and 8 and cpg", "tlr9 mcdonald dr", "et al. 2006 von", "al. 2006 von bernuth", "2006 von bernuth h", "von bernuth h et al.", "bernuth h et al. 2006", "et al. 2007 . in", "al. 2007 . in addition", "2007 . in addition to", ". in addition to tlr", "in addition to tlr nfkb", "addition to tlr nfkb signaling", "to tlr nfkb signaling axis", "tlr nfkb signaling axis the", "nfkb signaling axis the endosomic", "signaling axis the endosomic tlr7", "axis the endosomic tlr7 9", "the endosomic tlr7 9 activate", "endosomic tlr7 9 activate ifn", "tlr7 9 activate ifn alpha/beta", "9 activate ifn alpha/beta and", "activate ifn alpha/beta and ifn", "ifn alpha/beta and ifn gamma", "alpha/beta and ifn gamma responses", "ifn gamma responses which", "gamma responses which have", "responses which have been", "which have been also impaired", "have been also impaired in", "been also impaired in irak4", "also impaired in irak4 deficient", "impaired in irak4 deficient pbmc", "irak4 deficient pbmc yang", "deficient pbmc yang k", "pbmc yang k et", "yang k et al. 2005", "k et al. 2005 .", "et al. 2005 . however", "2005 . however ifn", ". however ifn alpha/beta", "however ifn alpha/beta and", "alpha/beta and ifn gamma production", "and ifn gamma production in", "ifn gamma production in response", "gamma production in response to", "production in response to 9", "in response to 9 of", "response to 9 of 11", "to 9 of 11 viruses", "9 of 11 viruses tested", "of 11 viruses tested was", "11 viruses tested was normal", "viruses tested was normal or", "tested was normal or weakly", "was normal or weakly affected", "normal or weakly affected in", "or weakly affected in irak", "weakly affected in irak 4", "affected in irak 4 deficient", "in irak 4 deficient blood", "irak 4 deficient blood cells", "deficient blood cells suggesting", "blood cells suggesting that", "cells suggesting that irak", "suggesting that irak 4 deficient", "that irak 4 deficient patients", "irak 4 deficient patients may", "4 deficient patients may control", "deficient patients may control viral", "patients may control viral infections", "may control viral infections by", "control viral infections by tlr7", "viral infections by tlr7 9", "infections by tlr7 9 independent", "by tlr7 9 independent production", "tlr7 9 independent production of", "9 independent production of ifns", "production of ifns yang", "of ifns yang k", "ifns yang k et", "et al. 2005 . so", "al. 2005 . so it", "2005 . so it is", ". so it is not", "so it is not yet", "it is not yet possible", "is not yet possible to", "not yet possible to annotate", "yet possible to annotate a", "possible to annotate a definitive", "to annotate a definitive molecular", "annotate a definitive molecular pathway", "a definitive molecular pathway between", "definitive molecular pathway between irak", "molecular pathway between irak 4", "pathway between irak 4 deficiency", "between irak 4 deficiency and", "irak 4 deficiency and changes", "4 deficiency and changes in", "deficiency and changes in tlr7", "and changes in tlr7 9", "changes in tlr7 9 signaling." ] }, { "record_id": "GLY_000594_1_1018", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5607763", "r hsa", "hsa 5607763", "r hsa 5607763" ] }, { "record_id": "GLY_000594_1_1018", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dectin 1", "induces nfat", "nfat activation", "clec7a dectin", "1 induces", "induces nfat activation", "clec7a dectin 1", "dectin 1 induces", "1 induces nfat", "dectin 1 induces nfat", "1 induces nfat activation", "signals through", "through the", "the classic", "classic calcineurin/nfat", "calcineurin/nfat pathway", "pathway through", "through syk", "syk activation", "activation phospholipase", "phospholipase c", "c gamma", "gamma 2", "leading to", "to increased", "increased soluble", "soluble ip3", "inositol trisphosphate", "trisphosphate .", ". ip3", "ip3 is", "is able", "able to", "to bind", "bind endoplasmic", "endoplasmic ca2+", "ca2+ channels", "resulting in", "in an", "an influx", "influx of", "of ca2+", "ca2+ into", "into the", "the cytoplasm.", "cytoplasm. this", "this increase", "increase in", "in calcium", "calcium concentration", "concentration induces", "induces calcineurin", "calcineurin activation", "activation and", "and consequently", "dephosphorylation of", "of nfat", "nfat 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increase in", "this increase in calcium", "increase in calcium concentration", "in calcium concentration induces", "calcium concentration induces calcineurin", "concentration induces calcineurin activation", "induces calcineurin activation and", "calcineurin activation and consequently", "and consequently dephosphorylation", "consequently dephosphorylation of", "dephosphorylation of nfat and", "of nfat and its", "nfat and its translocation", "and its translocation into", "its translocation into the", "translocation into the nucleus", "the nucleus triggering", "nucleus triggering gene", "triggering gene transcription and", "gene transcription and extracellular", "transcription and extracellular release", "and extracellular release of", "extracellular release of interleukin", "release of interleukin 2", "interleukin 2 plato", "2 plato et", "plato et al. 2013", "al. 2013 goodridge", "2013 goodridge et", "goodridge et al. 2007", "al. 2007 mourao", "2007 mourao sa", "mourao sa et al.", "sa et al. 2011", "et al. 2011 .", "dectin 1 signals through", "1 signals through the", "signals through the classic calcineurin/nfat", "through the classic calcineurin/nfat pathway", "the classic calcineurin/nfat pathway through", "classic calcineurin/nfat pathway through syk", "calcineurin/nfat pathway through syk activation", "pathway through syk activation phospholipase", "through syk activation phospholipase c", "syk activation phospholipase c gamma", "activation phospholipase c gamma 2", "c gamma 2 plcg2", "2 plcg2 leading", "plcg2 leading to increased", "leading to increased soluble ip3", "increased soluble ip3 inositol", "soluble ip3 inositol trisphosphate", "ip3 inositol trisphosphate .", "inositol trisphosphate . ip3 is", "trisphosphate . ip3 is able", ". ip3 is able to", "ip3 is able to bind", "is able to bind endoplasmic", "able to bind endoplasmic ca2+", "to bind endoplasmic ca2+ channels", "endoplasmic ca2+ channels resulting", "ca2+ channels resulting in", "channels resulting in an", "resulting in an influx of", "in an influx of ca2+", "an influx of ca2+ into", "influx of ca2+ into the", "of ca2+ into the cytoplasm.", "ca2+ into the cytoplasm. this", "into the cytoplasm. this increase", "the cytoplasm. this increase in", "cytoplasm. this increase in calcium", "this increase in calcium concentration", "increase in calcium concentration induces", "in calcium concentration induces calcineurin", "calcium concentration induces calcineurin activation", "concentration induces calcineurin activation and", "induces calcineurin activation and consequently", "activation and consequently dephosphorylation", "and consequently dephosphorylation of", "consequently dephosphorylation of nfat", "dephosphorylation of nfat and its", "of nfat and its translocation", "nfat and its translocation into", "and its translocation into the", "its translocation into the nucleus", "into the nucleus triggering", "the nucleus triggering gene", "nucleus triggering gene transcription", "triggering gene transcription and extracellular", "gene transcription and extracellular release", "transcription and extracellular release of", "and extracellular release of interleukin", "extracellular release of interleukin 2", "of interleukin 2 plato", "interleukin 2 plato et", "2 plato et al.", "et al. 2013 goodridge", "al. 2013 goodridge et", "2013 goodridge et al.", "et al. 2007 mourao", "al. 2007 mourao sa", "2007 mourao sa et", "mourao sa et al. 2011", "sa et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1019", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5610787", "r hsa", "hsa 5610787", "r hsa 5610787" ] }, { "record_id": "GLY_000594_1_1019", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hedgehog 'off'", "'off' state", "hedgehog 'off' state", "hedgehog is", "is a", "a secreted", "secreted morphogen", "morphogen that", "that has", "has evolutionarily", "evolutionarily conserved", "conserved roles", "roles in", "in body", "body organization", "organization by", "by regulating", "regulating the", "the activity", "activity of", "of the", "the ci/gli", "ci/gli transcription", "transcription factor", "factor family.", "family. in", "in drosophila", "drosophila in", "in the", "the absence", "absence of", "of hh", "hh signaling", "full length", "length ci", "ci is", "is partially", "partially degraded", "degraded by", "by the", "the proteasome", "proteasome to", "to generate", "generate a", "a truncated", "truncated repressor", "repressor form", "form that", "that translocates", "translocates to", "to the", "the nucleus", "nucleus to", "to represses", "represses hh", "hh responsive", "responsive genes.", "genes. binding", "binding of", "hh ligand", "ligand to", "the patched", "receptor allows", "allows the", "the 7", "7 pass", "pass transmembrane", "transmembrane protein", "protein smoothened", "to be", "be activated", "activated in", "in 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              while many", "many of", "the core", "core components", "components of", "signaling are", "are conserved", "conserved from", "from flies", "flies to", "to humans", "the pathways", "pathways do", "do show", "show points", "points of", "of significant", "significant divergence.", "divergence. notably", "the human", "human genome", "genome encodes", "encodes three", "three ci", "ci homologues", "2 and", "and 3", "3 that", "that each", "each play", "play slightly", "slightly different", "different roles", "in regulating", "regulating hh", "genes. gli3", "gli3 is", "is the", "the primary", "primary repressor", "repressor of", "signaling in", "in vertebrates", "and is", "is converted", "converted to", "the truncated", "truncated gli3r", "gli3r repressor", "form in", "of hh.", "hh. gli2", "gli2 is", "a potent", "potent activator", "activator of", "of transcription", "transcription in", "the presence", "presence of", "hh but", "but contributes", "contributes only", "only minimally", "minimally to", "the repression", "repression function.", "function. while", "while a", "a minor", "minor fraction", "fraction of", "of gli2", "gli2 protein", "protein is", "is processed", "processed into", "into the", "the repressor", "the majority", "majority is", "is either", "either fully", "fully degraded", "proteasome or", "or sequestered", "sequestered in", "length form", "the cytosol", "cytosol by", "by protein", "protein protein", "protein interactions.", "interactions. gli1", "gli1 lacks", "lacks the", "repression domain", "domain and", "and appears", "appears to", "be an", "an obligate", "obligate transcriptional", "transcriptional activator", "in briscoe", "2013 .
              ", ".
              vertebrate", "vertebrate but", "but not", "not fly", "fly hh", "signaling also", "also depends", "depends on", "on the", "the movement", "movement of", "of pathway", "pathway components", "components through", "through the", "primary cilium.", "cilium. the", "primary cilium", "cilium is", "a non", "non motile", "motile microtubule", "microtubule based", "based structure", "structure whose", "whose construction", "construction and", "and maintenance", "maintenance depends", "on intraflagellar", "intraflagellar transport", "ift .", ". anterograde", "anterograde ift", "ift moves", "moves molecules", "molecules from", "from the", "the ciliary", "ciliary base", "base along", "along the", "the axoneme", "axoneme to", "ciliary tip", "tip in", "in a", "a manner", "manner that", "that requires", "requires the", "the microtubule", "microtubule plus", "plus end", "end directed", "directed kinesin", "kinesin kif3", "kif3 motor", "motor complex", "complex and", "and the", "the ift", "ift b", "b protein", "protein complex", "while retrograde", "retrograde ift", "ift back", "back to", "base depends", "the minus", "minus end", "directed dynein", "dynein motor", "motor and", "ift a", "a complex.", "complex. genetic", "genetic screens", "screens have", "have identified", "identified a", "a number", "number of", "of cilia", "cilia related", "related proteins", "proteins that", "that are", "are required", "required both", "both to", "to maintain", "maintain hh", "hh in", "the 'off'", "state and", "and to", "to transduce", "transduce the", "the signal", "signal when", "when the", "the pathway", "pathway is", "is activated", "in hui", "hui and", "and angers", "goetz and", "and anderson", "2010 .", "hedgehog is a", "is a secreted", "a secreted morphogen", "secreted morphogen that", "morphogen that has", "that has evolutionarily", "has evolutionarily conserved", "evolutionarily conserved roles", "conserved roles in", "roles in body", "in body organization", "body organization by", "organization by regulating", "by regulating the", "regulating the activity", "the activity of", "activity of the", "of the ci/gli", "the ci/gli transcription", "ci/gli transcription factor", "transcription factor family.", "factor family. in", "family. in drosophila", "in drosophila in", "drosophila in the", "in the absence", "the absence of", "absence of hh", "of hh signaling", "signaling full", "full length ci", "length ci is", "ci is partially", "is partially degraded", "partially degraded by", "degraded by the", "by the proteasome", "the proteasome to", "proteasome to generate", "to generate a", "generate a truncated", "a truncated repressor", "truncated repressor form", "repressor form that", "form that translocates", "that translocates to", "translocates to the", "to the nucleus", "the nucleus to", "nucleus to represses", "to represses hh", "represses hh responsive", "hh responsive genes.", "responsive genes. binding", "genes. binding of", "binding of hh", "of hh ligand", "hh ligand to", "ligand to the", "to the patched", "patched ptc", "ptc receptor", "receptor allows the", "allows the 7", "the 7 pass", "7 pass transmembrane", "pass transmembrane protein", "transmembrane protein smoothened", "smoothened smo", "smo to", "to be activated", "be activated in", "activated in an", "in an unknown", "an unknown manner", "manner disrupting", "disrupting the partial", "the partial proteolysis", "partial proteolysis of", "proteolysis of ci", "of ci and", "ci and allowing", "and allowing the", "allowing the full", "the full length", "full length activator", "length activator form", "activator form to", "form to accumulate", "accumulate reviewed", "reviewed in ingham", "in ingham et", "ingham et al", "al 2011", "2011 briscoe", "briscoe and therond", "therond 2013", ".
              while", "
              while many of", "many of the", "of the core", "the core components", "core components of", "components of hh", "hh signaling are", "signaling are conserved", "are conserved from", "conserved from flies", "from flies to", "flies to humans", "humans the", "the pathways do", "pathways do show", "do show points", "show points of", "points of significant", "of significant divergence.", "significant divergence. notably", "notably the", "the human genome", "human genome encodes", "genome encodes three", "encodes three ci", "three ci homologues", "homologues gli1", "gli1 2", "2 and 3", "and 3 that", "3 that each", "that each play", "each play slightly", "play slightly different", "slightly different roles", "different roles in", "roles in regulating", "in regulating hh", "regulating hh responsive", "responsive genes. gli3", "genes. gli3 is", "gli3 is the", "is the primary", "the primary repressor", "primary repressor of", "repressor of hh", "hh signaling in", "signaling in vertebrates", "vertebrates and", "and is converted", "is converted to", "converted to the", "to the truncated", "the truncated gli3r", "truncated gli3r repressor", "gli3r repressor form", "repressor form in", "form in the", "absence of hh.", "of hh. gli2", "hh. gli2 is", "gli2 is a", "is a potent", "a potent activator", "potent activator of", "activator of transcription", "of transcription in", "transcription in the", "in the presence", "the presence of", "presence of hh", "of hh but", "hh but contributes", "but contributes only", "contributes only minimally", "only minimally to", "minimally to the", "to the repression", "the repression function.", "repression function. while", "function. while a", "while a minor", "a minor fraction", "minor fraction of", "fraction of gli2", "of gli2 protein", "gli2 protein is", "protein is processed", "is processed into", "processed into the", "into the repressor", "the repressor form", "hh the", "the majority is", "majority is either", "is either fully", "either fully degraded", "fully degraded by", "the proteasome or", "proteasome or sequestered", "or sequestered in", "sequestered in the", "in the full", "full length form", "length form in", "in the cytosol", "the cytosol by", "cytosol by protein", "by protein protein", "protein protein interactions.", "protein interactions. gli1", "interactions. gli1 lacks", "gli1 lacks the", "lacks the repression", "the repression domain", "repression domain and", "domain and appears", "and appears to", "appears to be", "to be an", "be an obligate", "an obligate transcriptional", "obligate transcriptional activator", "activator reviewed", "reviewed in briscoe", "in briscoe and", "2013 .
              vertebrate", ".
              vertebrate but", "vertebrate but not", "but not fly", "not fly hh", "fly hh signaling", "hh signaling also", "signaling also depends", "also depends on", "depends on the", "on the movement", "the movement of", "movement of pathway", "of pathway components", "pathway components through", "components through the", "through the primary", "the primary cilium.", "primary cilium. the", "cilium. the primary", "the primary cilium", "primary cilium is", "cilium is a", "is a non", "a non motile", "non motile microtubule", "motile microtubule based", "microtubule based structure", "based structure whose", "structure whose construction", "whose construction and", "construction and maintenance", "and maintenance depends", "maintenance depends on", "depends on intraflagellar", "on intraflagellar transport", "transport ift", "ift . anterograde", ". anterograde ift", "anterograde ift moves", "ift moves molecules", "moves molecules from", "molecules from the", "from the ciliary", "the ciliary base", "ciliary base along", "base along the", "along the axoneme", "the axoneme to", "axoneme to the", "to the ciliary", "the ciliary tip", "ciliary tip in", "tip in a", "in a manner", "a manner that", "manner that requires", "that requires the", "requires the microtubule", "the microtubule plus", "microtubule plus end", "plus end directed", "end directed kinesin", "directed kinesin kif3", "kinesin kif3 motor", "kif3 motor complex", "motor complex and", "complex and the", "and the ift", "the ift b", "ift b protein", "b protein complex", "complex while", "while retrograde ift", "retrograde ift back", "ift back to", "back to the", "ciliary base depends", "base depends on", "on the minus", "the minus end", "minus end directed", "end directed dynein", "directed dynein motor", "dynein motor and", "motor and the", "the ift a", "ift a complex.", "a complex. genetic", "complex. genetic screens", "genetic screens have", "screens have identified", "have identified a", "identified a number", "a number of", "number of cilia", "of cilia related", "cilia related proteins", "related proteins that", "proteins that are", "that are required", "are required both", "required both to", "both to maintain", "to maintain hh", "maintain hh in", "hh in the", "in the 'off'", "the 'off' state", "'off' state and", "state and to", "and to transduce", "to transduce the", "transduce the signal", "the signal when", "signal when the", "when the pathway", "the pathway is", "pathway is activated", "activated reviewed", "reviewed in hui", "in hui and", "hui and angers", "angers 2011", "2011 goetz", "goetz and anderson", "anderson 2010", "hedgehog is a secreted", "is a secreted morphogen", "a secreted morphogen that", "secreted morphogen that has", "morphogen that has evolutionarily", "that has evolutionarily conserved", "has evolutionarily conserved roles", "evolutionarily conserved roles in", "conserved roles in body", "roles in body organization", "in body organization by", "body organization by regulating", "organization by regulating the", "by regulating the activity", "regulating the activity of", "the activity of the", "activity of the ci/gli", "of the ci/gli transcription", "the ci/gli transcription factor", "ci/gli transcription factor family.", "transcription factor family. in", "factor family. in drosophila", "family. in drosophila in", "in drosophila in the", "drosophila in the absence", "in the absence of", "the absence of hh", "absence of hh signaling", "hh signaling full", "signaling full length", "full length ci is", "length ci is partially", "ci is partially degraded", "is partially degraded by", "partially degraded by the", "degraded by the proteasome", "by the proteasome to", "the proteasome to generate", "proteasome to generate a", "to generate a truncated", "generate a truncated repressor", "a truncated repressor form", "truncated repressor form that", "repressor form that translocates", "form that translocates to", "that translocates to the", "translocates to the nucleus", "to the nucleus to", "the nucleus to represses", "nucleus to represses hh", "to represses hh responsive", "represses hh responsive genes.", "hh responsive genes. binding", "responsive genes. binding of", "genes. binding of hh", "binding of hh ligand", "of hh ligand to", "hh ligand to the", "ligand to the patched", "the patched ptc", "ptc receptor allows", "receptor allows the 7", "allows the 7 pass", "the 7 pass transmembrane", "7 pass transmembrane protein", "pass transmembrane protein smoothened", "protein smoothened smo", "smo to be", "to be activated in", "be activated in an", "activated in an unknown", "in an unknown manner", "unknown manner disrupting", "manner disrupting the", "disrupting the partial proteolysis", "the partial proteolysis of", "partial proteolysis of ci", "proteolysis of ci and", "of ci and allowing", "ci and allowing the", "and allowing the full", "allowing the full length", "the full length activator", "full length activator form", "length activator form to", "activator form to accumulate", "to accumulate reviewed", "accumulate reviewed in", "reviewed in ingham et", "in ingham et al", "et al 2011", "2011 briscoe and", "and therond 2013", "therond 2013 .", "2013 .
              while", ".
              while many", "
              while many of the", "many of the core", "of the core components", "the core components of", "core components of hh", "components of hh signaling", "of hh signaling are", "hh signaling are conserved", "signaling are conserved from", "are conserved from flies", "conserved from flies to", "from flies to humans", "to humans the", "humans the pathways", "the pathways do show", "pathways do show points", "do show points of", "show points of significant", "points of significant divergence.", "of significant divergence. notably", "divergence. notably the", "notably the human", "the human genome encodes", "human genome encodes three", "genome encodes three ci", "encodes three ci homologues", "ci homologues gli1", "gli1 2 and", "2 and 3 that", "and 3 that each", "3 that each play", "that each play slightly", "each play slightly different", "play slightly different roles", "slightly different roles in", "different roles in regulating", "roles in regulating hh", "in regulating hh responsive", "regulating hh responsive genes.", "hh responsive genes. gli3", "responsive genes. gli3 is", "genes. gli3 is the", "gli3 is the primary", "is the primary repressor", "the primary repressor of", "primary repressor of hh", "repressor of hh signaling", "of hh signaling in", "hh signaling in vertebrates", "in vertebrates and", "vertebrates and is", "and is converted to", "is converted to the", "converted to the truncated", "to the truncated gli3r", "the truncated gli3r repressor", "truncated gli3r repressor form", "gli3r repressor form in", "repressor form in the", "form in the absence", "the absence of hh.", "absence of hh. gli2", "of hh. gli2 is", "hh. gli2 is a", "gli2 is a potent", "is a potent activator", "a potent activator of", "potent activator of transcription", "activator of transcription in", "of transcription in the", "transcription in the presence", "in the presence of", "the presence of hh", "presence of hh but", "of hh but contributes", "hh but contributes only", "but contributes only minimally", "contributes only minimally to", "only minimally to the", "minimally to the repression", "to the repression function.", "the repression function. while", "repression function. while a", "function. while a minor", "while a minor fraction", "a minor fraction of", "minor fraction of gli2", "fraction of gli2 protein", "of gli2 protein is", "gli2 protein is processed", "protein is processed into", "is processed into the", "processed into the repressor", "into the repressor form", "the repressor form in", "of hh the", "hh the majority", "the majority is either", "majority is either fully", "is either fully degraded", "either fully degraded by", "fully degraded by the", "by the proteasome or", "the proteasome or sequestered", "proteasome or sequestered in", "or sequestered in the", "sequestered in the full", "in the full length", "the full length form", "full length form in", "length form in the", "form in the cytosol", "in the cytosol by", "the cytosol by protein", "cytosol by protein protein", "by protein protein interactions.", "protein protein interactions. gli1", "protein interactions. gli1 lacks", "interactions. gli1 lacks the", "gli1 lacks the repression", "lacks the repression domain", "the repression domain and", "repression domain and appears", "domain and appears to", "and appears to be", "appears to be an", "to be an obligate", "be an obligate transcriptional", "an obligate transcriptional activator", "transcriptional activator reviewed", "activator reviewed in", "reviewed in briscoe and", "in briscoe and therond", "therond 2013 .
              ", "2013 .
              vertebrate but", ".
              vertebrate but not", "vertebrate but not fly", "but not fly hh", "not fly hh signaling", "fly hh signaling also", "hh signaling also depends", "signaling also depends on", "also depends on the", "depends on the movement", "on the movement of", "the movement of pathway", "movement of pathway components", "of pathway components through", "pathway components through the", "components through the primary", "through the primary cilium.", "the primary cilium. the", "primary cilium. the primary", "cilium. the primary cilium", "the primary cilium is", "primary cilium is a", "cilium is a non", "is a non motile", "a non motile microtubule", "non motile microtubule based", "motile microtubule based structure", "microtubule based structure whose", "based structure whose construction", "structure whose construction and", "whose construction and maintenance", "construction and maintenance depends", "and maintenance depends on", "maintenance depends on intraflagellar", "depends on intraflagellar transport", "intraflagellar transport ift", "transport ift .", "ift . anterograde ift", ". anterograde ift moves", "anterograde ift moves molecules", "ift moves molecules from", "moves molecules from the", "molecules from the ciliary", "from the ciliary base", "the ciliary base along", "ciliary base along the", "base along the axoneme", "along the axoneme to", "the axoneme to the", "axoneme to the ciliary", "to the ciliary tip", "the ciliary tip in", "ciliary tip in a", "tip in a manner", "in a manner that", "a manner that requires", "manner that requires the", "that requires the microtubule", "requires the microtubule plus", "the microtubule plus end", "microtubule plus end directed", "plus end directed kinesin", "end directed kinesin kif3", "directed kinesin kif3 motor", "kinesin kif3 motor complex", "kif3 motor complex and", "motor complex and the", "complex and the ift", "and the ift b", "the ift b protein", "ift b protein complex", "protein complex while", "complex while retrograde", "while retrograde ift back", "retrograde ift back to", "ift back to the", "back to the ciliary", "to the ciliary base", "the ciliary base depends", "ciliary base depends on", "base depends on the", "depends on the minus", "on the minus end", "the minus end directed", "minus end directed dynein", "end directed dynein motor", "directed dynein motor and", "dynein motor and the", "motor and the ift", "and the ift a", "the ift a complex.", "ift a complex. genetic", "a complex. genetic screens", "complex. genetic screens have", "genetic screens have identified", "screens have identified a", "have identified a number", "identified a number of", "a number of cilia", "number of cilia related", "of cilia related proteins", "cilia related proteins that", "related proteins that are", "proteins that are required", "that are required both", "are required both to", "required both to maintain", "both to maintain hh", "to maintain hh in", "maintain hh in the", "hh in the 'off'", "in the 'off' state", "the 'off' state and", "'off' state and to", "state and to transduce", "and to transduce the", "to transduce the signal", "transduce the signal when", "the signal when the", "signal when the pathway", "when the pathway is", "the pathway is activated", "is activated reviewed", "activated reviewed in", "reviewed in hui and", "in hui and angers", "and angers 2011", "2011 goetz and", "and anderson 2010", "anderson 2010 .", "hedgehog is a secreted morphogen", "is a secreted morphogen that", "a secreted morphogen that has", "secreted morphogen that has evolutionarily", "morphogen that has evolutionarily conserved", "that has evolutionarily conserved roles", "has evolutionarily conserved roles in", "evolutionarily conserved roles in body", "conserved roles in body organization", "roles in body organization by", "in body organization by regulating", "body organization by regulating the", "organization by regulating the activity", "by regulating the activity of", "regulating the activity of the", "the activity of the ci/gli", "activity of the ci/gli transcription", "of the ci/gli transcription factor", "the ci/gli transcription factor family.", "ci/gli transcription factor family. in", "transcription factor family. in drosophila", "factor family. in drosophila in", "family. in drosophila in the", "in drosophila in the absence", "drosophila in the absence of", "in the absence of hh", "the absence of hh signaling", "of hh signaling full", "hh signaling full length", "signaling full length ci", "full length ci is partially", "length ci is partially degraded", "ci is partially degraded by", "is partially degraded by the", "partially degraded by the proteasome", "degraded by the proteasome to", "by the proteasome to generate", "the proteasome to generate a", "proteasome to generate a truncated", "to generate a truncated repressor", "generate a truncated repressor form", "a truncated repressor form that", "truncated repressor form that translocates", "repressor form that translocates to", "form that translocates to the", "that translocates to the nucleus", "translocates to the nucleus to", "to the nucleus to represses", "the nucleus to represses hh", "nucleus to represses hh responsive", "to represses hh responsive genes.", "represses hh responsive genes. binding", "hh responsive genes. binding of", "responsive genes. binding of hh", "genes. binding of hh ligand", "binding of hh ligand to", "of hh ligand to the", "hh ligand to the patched", "to the patched ptc", "patched ptc receptor", "ptc receptor allows the", "receptor allows the 7 pass", "allows the 7 pass transmembrane", "the 7 pass transmembrane protein", "7 pass transmembrane protein smoothened", "transmembrane protein smoothened smo", "smoothened smo to", "smo to be activated", "to be activated in an", "be activated in an unknown", "activated in an unknown manner", "an unknown manner disrupting", "unknown manner disrupting the", "manner disrupting the partial", "disrupting the partial proteolysis of", "the partial proteolysis of ci", "partial proteolysis of ci and", "proteolysis of ci and allowing", "of ci and allowing the", "ci and allowing the full", "and allowing the full length", "allowing the full length activator", "the full length activator form", "full length activator form to", "length activator form to accumulate", "form to accumulate reviewed", "to accumulate reviewed in", "accumulate reviewed in ingham", "reviewed in ingham et al", "ingham et al 2011", "al 2011 briscoe", "2011 briscoe and therond", "briscoe and therond 2013", "and therond 2013 .", "2013 .
              while many", ".
              while many of", "
              while many of the core", "many of the core components", "of the core components of", "the core components of hh", "core components of hh signaling", "components of hh signaling are", "of hh signaling are conserved", "hh signaling are conserved from", "signaling are conserved from flies", "are conserved from flies to", "conserved from flies to humans", "flies to humans the", "to humans the pathways", "humans the pathways do", "the pathways do show points", "pathways do show points of", "do show points of significant", "show points of significant divergence.", "points of significant divergence. notably", "significant divergence. notably the", "divergence. notably the human", "notably the human genome", "the human genome encodes three", "human genome encodes three ci", "genome encodes three ci homologues", "three ci homologues gli1", "homologues gli1 2", "gli1 2 and 3", "2 and 3 that each", "and 3 that each play", "3 that each play slightly", "that each play slightly different", "each play slightly different roles", "play slightly different roles in", "slightly different roles in regulating", "different roles in regulating hh", "roles in regulating hh responsive", "in regulating hh responsive genes.", "regulating hh responsive genes. gli3", "hh responsive genes. gli3 is", "responsive genes. gli3 is the", "genes. gli3 is the primary", "gli3 is the primary repressor", "is the primary repressor of", "the primary repressor of hh", "primary repressor of hh signaling", "repressor of hh signaling in", "of hh signaling in vertebrates", "signaling in vertebrates and", "in vertebrates and is", "vertebrates and is converted", "and is converted to the", "is converted to the truncated", "converted to the truncated gli3r", "to the truncated gli3r repressor", "the truncated gli3r repressor form", "truncated gli3r repressor form in", "gli3r repressor form in the", "repressor form in the absence", "form in the absence of", "in the absence of hh.", "the absence of hh. gli2", "absence of hh. gli2 is", "of hh. gli2 is a", "hh. gli2 is a potent", "gli2 is a potent activator", "is a potent activator of", "a potent activator of transcription", "potent activator of transcription in", "activator of transcription in the", "of transcription in the presence", "transcription in the presence of", "in the presence of hh", "the presence of hh but", "presence of hh but contributes", "of hh but contributes only", "hh but contributes only minimally", "but contributes only minimally to", "contributes only minimally to the", "only minimally to the repression", "minimally to the repression function.", "to the repression function. while", "the repression function. while a", "repression function. while a minor", "function. while a minor fraction", "while a minor fraction of", "a minor fraction of gli2", "minor fraction of gli2 protein", "fraction of gli2 protein is", "of gli2 protein is processed", "gli2 protein is processed into", "protein is processed into the", "is processed into the repressor", "processed into the repressor form", "into the repressor form in", "the repressor form in the", "absence of hh the", "of hh the majority", "hh the majority is", "the majority is either fully", "majority is either fully degraded", "is either fully degraded by", "either fully degraded by the", "fully degraded by the proteasome", "degraded by the proteasome or", "by the proteasome or sequestered", "the proteasome or sequestered in", "proteasome or sequestered in the", "or sequestered in the full", "sequestered in the full length", "in the full length form", "the full length form in", "full length form in the", "length form in the cytosol", "form in the cytosol by", "in the cytosol by protein", "the cytosol by protein protein", "cytosol by protein protein interactions.", "by protein protein interactions. gli1", "protein protein interactions. gli1 lacks", "protein interactions. gli1 lacks the", "interactions. gli1 lacks the repression", "gli1 lacks the repression domain", "lacks the repression domain and", "the repression domain and appears", "repression domain and appears to", "domain and appears to be", "and appears to be an", "appears to be an obligate", "to be an obligate transcriptional", "be an obligate transcriptional activator", "obligate transcriptional activator reviewed", "transcriptional activator reviewed in", "activator reviewed in briscoe", "reviewed in briscoe and therond", "and therond 2013 .
              ", "therond 2013 .
              vertebrate", "2013 .
              vertebrate but not", ".
              vertebrate but not fly", "vertebrate but not fly hh", "but not fly hh signaling", "not fly hh signaling also", "fly hh signaling also depends", "hh signaling also depends on", "signaling also depends on the", "also depends on the movement", "depends on the movement of", "on the movement of pathway", "the movement of pathway components", "movement of pathway components through", "of pathway components through the", "pathway components through the primary", "components through the primary cilium.", "through the primary cilium. the", "the primary cilium. the primary", "primary cilium. the primary cilium", "cilium. the primary cilium is", "the primary cilium is a", "primary cilium is a non", "cilium is a non motile", "is a non motile microtubule", "a non motile microtubule based", "non motile microtubule based structure", "motile microtubule based structure whose", "microtubule based structure whose construction", "based structure whose construction and", "structure whose construction and maintenance", "whose construction and maintenance depends", "construction and maintenance depends on", "and maintenance depends on intraflagellar", "maintenance depends on intraflagellar transport", "on intraflagellar transport ift", "intraflagellar transport ift .", "transport ift . anterograde", "ift . anterograde ift moves", ". anterograde ift moves molecules", "anterograde ift moves molecules from", "ift moves molecules from the", "moves molecules from the ciliary", "molecules from the ciliary base", "from the ciliary base along", "the ciliary base along the", "ciliary base along the axoneme", "base along the axoneme to", "along the axoneme to the", "the axoneme to the ciliary", "axoneme to the ciliary tip", "to the ciliary tip in", "the ciliary tip in a", "ciliary tip in a manner", "tip in a manner that", "in a manner that requires", "a manner that requires the", "manner that requires the microtubule", "that requires the microtubule plus", "requires the 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complex. genetic", "ift a complex. genetic screens", "a complex. genetic screens have", "complex. genetic screens have identified", "genetic screens have identified a", "screens have identified a number", "have identified a number of", "identified a number of cilia", "a number of cilia related", "number of cilia related proteins", "of cilia related proteins that", "cilia related proteins that are", "related proteins that are required", "proteins that are required both", "that are required both to", "are required both to maintain", "required both to maintain hh", "both to maintain hh in", "to maintain hh in the", "maintain hh in the 'off'", "hh in the 'off' state", "in the 'off' state and", "the 'off' state and to", "'off' state and to transduce", "state and to transduce the", "and to transduce the signal", "to transduce the signal when", "transduce the signal when the", "the signal when the pathway", "signal when the pathway is", "when the pathway is activated", "pathway is activated reviewed", "is activated reviewed in", "activated reviewed in hui", "reviewed in hui and angers", "hui and angers 2011", "angers 2011 goetz", "2011 goetz and anderson", "goetz and anderson 2010", "and anderson 2010 ." ] }, { "record_id": "GLY_000594_1_1020", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619045", "r hsa", "hsa 5619045", "r hsa 5619045" ] }, { "record_id": "GLY_000594_1_1020", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc34a2", "slc34a2 causes", "causes pulmonary", "pulmonary alveolar", "alveolar microlithiasis", "defective slc34a2 causes", "slc34a2 causes pulmonary", "causes pulmonary alveolar", "pulmonary alveolar microlithiasis", "microlithiasis palm", "defective slc34a2 causes pulmonary", "slc34a2 causes pulmonary alveolar", "causes pulmonary alveolar microlithiasis", "alveolar microlithiasis palm", "defective slc34a2 causes pulmonary alveolar", "slc34a2 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term", "term progressive", "progressive course", "resulting in", "in a", "a slow", "slow deterioration", "deterioration of", "of lung", "lung function", "corut et", "et al.", "al. 2006", "forster et", "al. 2013", "2013 .", "slc34a1 and 2", "and 2 encode", "2 encode na+/pi", "encode na+/pi cotransporters", "cotransporters which", "which cotransport divalent", "cotransport divalent phosphate", "phosphate po4", "pi with", "with 3 na+", "3 na+ ions.", "na+ ions. slc34a2", "ions. slc34a2 is", "slc34a2 is abundantly", "is abundantly expressed", "abundantly expressed in", "expressed in lung", "in lung and", "lung and to", "and to a", "to a lesser", "a lesser extent", "lesser extent in", "extent in tissues", "in tissues of", "tissues of epithelial", "of epithelial origin", "epithelial origin including", "origin including small", "including small intestine", "intestine pancreas", "pancreas prostate", "prostate and", "and kidney. defects", "kidney. defects in", "defects in slc34a2", "in slc34a2 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"rare disease characterised by", "disease characterised by the", "characterised by the deposition", "by the deposition of", "the deposition of calcium", "deposition of calcium phosphate", "of calcium phosphate microliths", "calcium phosphate microliths throughout", "phosphate microliths throughout the", "microliths throughout the lungs.", "throughout the lungs. the", "the lungs. the disease", "lungs. the disease follows", "the disease follows a", "disease follows a long", "follows a long term", "a long term progressive", "long term progressive course", "progressive course resulting", "course resulting in", "resulting in a slow", "in a slow deterioration", "a slow deterioration of", "slow deterioration of lung", "deterioration of lung function", "lung function corut", "function corut et", "corut et al. 2006", "al. 2006 forster", "2006 forster et", "forster et al. 2013", "et al. 2013 .", "slc34a1 and 2 encode na+/pi", "and 2 encode na+/pi cotransporters", "encode na+/pi cotransporters 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are", "defects in slc34a2 are a", "in slc34a2 are a cause", "slc34a2 are a cause of", "are a cause of pulmonary", "a cause of pulmonary alveolar", "cause of pulmonary alveolar microlithiasis", "microlithiasis palm mim:265100", "mim:265100 a rare", "265100 a rare", "a rare disease characterised by", "rare disease characterised by the", "disease characterised by the deposition", "characterised by the deposition of", "by the deposition of calcium", "the deposition of calcium phosphate", "deposition of calcium phosphate microliths", "of calcium phosphate microliths throughout", "calcium phosphate microliths throughout the", "phosphate microliths throughout the lungs.", "microliths throughout the lungs. the", "throughout the lungs. the disease", "the lungs. the disease follows", "lungs. the disease follows a", "the disease follows a long", "disease follows a long term", "follows a long term progressive", "a long term progressive course", "term progressive course resulting", "progressive course resulting in", "course resulting in a", "resulting in a slow deterioration", "in a slow deterioration of", "a slow deterioration of lung", "slow deterioration of lung function", "of lung function corut", "lung function corut et", "function corut et al.", "et al. 2006 forster", "al. 2006 forster et", "2006 forster et al.", "forster et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1021", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619046", "r hsa", "hsa 5619046", "r hsa 5619046" ] }, { "record_id": "GLY_000594_1_1021", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc26a4", "slc26a4 causes", "causes pendred", "pendred syndrome", "defective slc26a4 causes", "slc26a4 causes pendred", "causes pendred syndrome", "syndrome pds", "defective slc26a4 causes pendred", "slc26a4 causes pendred syndrome", "pendred syndrome pds", "defective slc26a4 causes pendred syndrome", "causes pendred syndrome pds", "solute carrier", "genes that", "that code", "code chloride", "exchanger proteins", "proteins are", "are in", "in the", "the slc4", "slc4 and", "and slc26", "slc26 families.", "families. slc26a4", "is thought", "thought to", "to act", "act as", "as a", "a chloride/anion", "chloride/anion exchanger", "exchanger but", "but in", "the thyroid", "thyroid and", "and inner", "inner ear", "it also", "also contributes", "contributes to", "to the", "the conditioning", "conditioning of", "of the", "the endolymphatic", "endolymphatic fluid", "fluid by", "by mediating", "mediating iodide", "transport. defects", "defects in", "in slc26a4", "slc26a4 can", "can cause", "cause pendred", "an autosomal", "autosomal recessive", "recessive disorder", "disorder characterised", "characterised by", "by congenital", "congenital sensorineural", "sensorineural hearing", "hearing loss", "loss in", "in association", "association with", "with thyroid", "thyroid goiter", "choi et", "et al.", "al. 2011", "pesce &", "& kopp", "kopp 2014", "2014 .", "carrier slc", "slc genes", "genes that code", "that code chloride", "chloride cl", "cl /bicarbonate", "/bicarbonate hco3", "exchanger proteins are", "proteins are in", "are in the", "in the slc4", "the slc4 and", "slc4 and slc26", "and slc26 families.", "slc26 families. slc26a4", "slc26a4 pendrin", "pendrin is", "is thought to", "thought to act", "to act as", "act as a", "as a chloride/anion", "a chloride/anion exchanger", "chloride/anion exchanger but", "exchanger but in", "but in the", "in the thyroid", "the thyroid and", "thyroid and inner", "and inner ear", "ear it", "it also contributes", "also contributes to", "contributes to the", "to the conditioning", "the conditioning of", "conditioning of the", "of the endolymphatic", "the endolymphatic fluid", "endolymphatic fluid by", "fluid by mediating", "by mediating iodide", "iodide i", "transport. defects in", "defects in slc26a4", "in slc26a4 can", "slc26a4 can cause", "can cause pendred", "cause pendred syndrome", "pds mim:274600", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder characterised", "disorder characterised by", "characterised by congenital", "by congenital sensorineural", "congenital sensorineural hearing", "sensorineural hearing loss", "hearing loss in", "loss in association", "in association with", "association with thyroid", "with thyroid goiter", "goiter choi", "choi et al.", "et al. 2011", "2011 pesce", "pesce & kopp", "& kopp 2014", "kopp 2014 .", "solute carrier slc", "slc genes that", "genes that code chloride", "code chloride cl", "hco3 exchanger", "exchanger proteins are in", "proteins are in the", "are in the slc4", "in the slc4 and", "the slc4 and slc26", "slc4 and slc26 families.", "and slc26 families. slc26a4", "families. slc26a4 pendrin", "pendrin is thought", "is thought to act", "thought to act as", "to act as a", "act as a chloride/anion", "as a chloride/anion exchanger", "a chloride/anion exchanger but", "chloride/anion exchanger but in", "exchanger but in the", "but in the thyroid", "in the thyroid and", "the thyroid and inner", "thyroid and inner ear", "inner ear it", "ear it also", "it also contributes to", "also contributes to the", "contributes to the conditioning", "to the conditioning of", "the conditioning of the", "conditioning of the endolymphatic", "of the endolymphatic fluid", "the endolymphatic fluid by", "endolymphatic fluid by mediating", "fluid by mediating iodide", "mediating iodide i", "i transport.", "transport. defects in slc26a4", "defects in slc26a4 can", "in slc26a4 can cause", "slc26a4 can cause pendred", "can cause pendred syndrome", "mim:274600 an", "274600 an", "an autosomal recessive disorder", "autosomal recessive disorder characterised", "recessive disorder characterised by", "disorder characterised by congenital", "characterised by congenital sensorineural", "by congenital sensorineural hearing", "congenital sensorineural hearing loss", "sensorineural hearing loss in", "hearing loss in association", "loss in association with", "in association with thyroid", "association with thyroid goiter", "thyroid goiter choi", "goiter choi et", "choi et al. 2011", "al. 2011 pesce", "2011 pesce &", "pesce & kopp 2014", "& kopp 2014 .", "carrier slc genes", "slc genes that code", "that code chloride cl", "chloride cl /bicarbonate", "cl /bicarbonate hco3", "hco3 exchanger proteins", "exchanger proteins are in the", "proteins are in the slc4", "are in the slc4 and", "in the slc4 and slc26", "the slc4 and slc26 families.", "slc4 and slc26 families. slc26a4", "slc26 families. slc26a4 pendrin", "slc26a4 pendrin is", "pendrin is thought to", "is thought to act as", "thought to act as a", "to act as a chloride/anion", "act as a chloride/anion exchanger", "as a chloride/anion exchanger but", "a chloride/anion exchanger but in", "chloride/anion exchanger but in the", "exchanger but in the thyroid", "but in the thyroid and", "in the thyroid and inner", "the thyroid and inner ear", "and inner ear it", "inner ear it also", "ear it also contributes", "it also contributes to the", "also contributes to the conditioning", "contributes to the conditioning of", "to the conditioning of the", "the conditioning of the endolymphatic", "conditioning of the endolymphatic fluid", "of the endolymphatic fluid by", "the endolymphatic fluid by mediating", "endolymphatic fluid by mediating iodide", "by mediating iodide i", "i transport. defects", "transport. defects in slc26a4 can", "defects in slc26a4 can cause", "in slc26a4 can cause pendred", "slc26a4 can cause pendred syndrome", "cause pendred syndrome pds", "syndrome pds mim:274600", "mim:274600 an autosomal", "274600 an autosomal", "an autosomal recessive disorder characterised", "autosomal recessive disorder characterised by", "recessive disorder characterised by congenital", "disorder characterised by congenital sensorineural", "characterised by congenital sensorineural hearing", "by congenital sensorineural hearing loss", "congenital sensorineural hearing loss in", "sensorineural hearing loss in association", "hearing loss in association with", "loss in association with thyroid", "in association with thyroid goiter", "with thyroid goiter choi", "thyroid goiter choi et", "goiter choi et al.", "et al. 2011 pesce", "al. 2011 pesce &", "2011 pesce & kopp", "pesce & kopp 2014 ." ] }, { "record_id": "GLY_000594_1_1022", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619049", "r hsa", "hsa 5619049", "r hsa 5619049" ] }, { "record_id": "GLY_000594_1_1022", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc40a1", "slc40a1 causes", "causes hemochromatosis", "hemochromatosis 4", "defective slc40a1 causes", "slc40a1 causes hemochromatosis", "causes hemochromatosis 4", "4 hfe4", "defective slc40a1 causes hemochromatosis", "slc40a1 causes hemochromatosis 4", "hemochromatosis 4 hfe4", "hfe4 macrophages", "defective slc40a1 causes hemochromatosis 4", "causes hemochromatosis 4 hfe4", "mtp1 aka", "aka ferroportin", "ferroportin or", "or ireg1", "is highly", "highly expressed", "expressed on", "on macrophages", "macrophages where", "where it", "it mediates", "mediates iron", "iron efflux", "efflux from", "from the", "the breakdown", "breakdown of", "of haem.", "haem. slc40a1", "slc40a1 colocalises", "colocalises with", "with ceruloplasmin", "which stablizes", "stablizes slc40a1", "slc40a1 and", "and is", "is necessary", "necessary for", "for the", "the efflux", "efflux reaction", "reaction to", "to occur.", "occur. six", "six copper", "copper ions", "ions are", "are required", "required by", "by ceruloplasmin", "ceruloplasmin as", "as a", "a cofactor.
              defects", "cofactor.
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              defects", "a cofactor.
              defects in", "cofactor.
              defects in slc40a1", "in slc40a1 can", "slc40a1 can cause", "can cause hemochromatosis", "cause hemochromatosis 4", "hfe4 mim:606069", "a disorder of", "disorder of iron", "of iron metabolism", "iron metabolism characterised", "metabolism characterised by", "characterised by iron", "by iron overload.", "iron overload. excess", "overload. excess iron", "excess iron is", "iron is deposited", "is deposited in", "deposited in a", "in a variety", "a variety of", "variety of organs", "of organs leading", "organs leading to", "leading to their", "to their failure", "failure resulting", "resulting in serious", "in serious illnesses", "serious illnesses including", "illnesses including cirrhosis", "cirrhosis hepatomas", "hepatomas diabetes", "diabetes cardiomyopathy", "cardiomyopathy arthritis", "arthritis and hypogonadotropic", "and hypogonadotropic hypogonadism.", "hypogonadotropic hypogonadism. severe", "hypogonadism. severe effects", "severe effects of", "effects of the", "of the disease", "the disease don't", "disease don't usually", "don't usually appear", "usually appear until", "appear until after", "until after decades", "after decades of", "decades of progressive", "of progressive iron", "progressive iron overloading", "overloading de", "de domenico et", "domenico et al.", "et al. 2005", "2005 2006", "2006 2011", "2011 kaplan", "kaplan et al.", "et al. 2011", "al. 2011 .", "slc40a1 mtp1 aka", "mtp1 aka ferroportin or", "aka ferroportin or ireg1", "or ireg1 is", "ireg1 is highly", "is highly expressed on", "highly expressed on macrophages", "expressed on macrophages where", "on macrophages where it", "macrophages where it mediates", "where it mediates iron", "it mediates iron efflux", "mediates iron efflux from", "iron efflux from the", "efflux from the breakdown", "from the breakdown of", "the breakdown of haem.", "breakdown of haem. slc40a1", "of haem. slc40a1 colocalises", "haem. slc40a1 colocalises with", "slc40a1 colocalises with ceruloplasmin", "with ceruloplasmin cp", "cp which stablizes", "which stablizes slc40a1 and", "stablizes slc40a1 and is", "slc40a1 and is necessary", "and is necessary for", "is necessary for the", "necessary for the efflux", "for the efflux reaction", "the efflux reaction to", "efflux reaction to occur.", "reaction to occur. six", "to occur. six copper", "occur. six copper ions", "six copper ions are", "copper ions are required", "ions are required by", "are required by ceruloplasmin", "required by ceruloplasmin as", "by ceruloplasmin as a", "ceruloplasmin as a cofactor.
              defects", "as a cofactor.
              defects in", "a cofactor.
              defects in slc40a1", "cofactor.
              defects in slc40a1 can", "in slc40a1 can cause", "slc40a1 can cause hemochromatosis", "can cause hemochromatosis 4", "mim:606069 a", "606069 a", "a disorder of iron", "disorder of iron metabolism", "of iron metabolism characterised", "iron metabolism characterised by", "metabolism characterised by iron", "characterised by iron overload.", "by iron overload. excess", "iron overload. excess iron", "overload. excess iron is", "excess iron is deposited", "iron is deposited in", "is deposited in a", "deposited in a variety", "in a variety of", "a variety of organs", "variety of organs leading", "of organs leading to", "organs leading to their", "leading to their failure", "their failure resulting", "failure resulting in", "resulting in serious illnesses", "in serious illnesses including", "serious illnesses including cirrhosis", "including cirrhosis hepatomas", "cardiomyopathy arthritis and", "arthritis and hypogonadotropic hypogonadism.", "and hypogonadotropic hypogonadism. severe", "hypogonadotropic hypogonadism. severe effects", "hypogonadism. severe effects of", "severe effects of the", "effects of the disease", "of the disease don't", "the disease don't usually", "disease don't usually appear", "don't usually appear until", "usually appear until after", "appear until after decades", "until after decades of", "after decades of progressive", "decades of progressive iron", "of progressive iron overloading", "iron overloading de", "overloading de domenico", "de domenico et al.", "domenico et al. 2005", "al. 2005 2006", "2011 kaplan et", "kaplan et al. 2011", "et al. 2011 .", "slc40a1 mtp1 aka ferroportin", "mtp1 aka ferroportin or ireg1", "ferroportin or ireg1 is", "or ireg1 is highly", "ireg1 is highly expressed", "is highly expressed on macrophages", "highly expressed on macrophages where", "expressed on macrophages where it", "on macrophages where it mediates", "macrophages where it mediates iron", "where it mediates iron efflux", "it mediates iron efflux from", "mediates iron efflux from the", "iron efflux from the breakdown", "efflux from the breakdown of", "from the breakdown of haem.", "the breakdown of haem. slc40a1", "breakdown of haem. slc40a1 colocalises", "of haem. slc40a1 colocalises with", "haem. slc40a1 colocalises with ceruloplasmin", "colocalises with ceruloplasmin cp", "ceruloplasmin cp which", "cp which stablizes slc40a1", "which stablizes slc40a1 and is", "stablizes slc40a1 and is necessary", "slc40a1 and is necessary for", "and is necessary for the", "is necessary for the efflux", "necessary for the efflux reaction", "for the efflux reaction to", "the efflux reaction to occur.", "efflux reaction to occur. six", "reaction to occur. six copper", "to occur. six copper ions", "occur. six copper ions are", "six copper ions are required", "copper ions are required by", "ions are required by ceruloplasmin", "are required by ceruloplasmin as", "required by ceruloplasmin as a", "by ceruloplasmin as a cofactor.
              defects", "ceruloplasmin as a cofactor.
              defects in", "as a cofactor.
              defects in slc40a1", "a cofactor.
              defects in slc40a1 can", "cofactor.
              defects in slc40a1 can cause", "in slc40a1 can cause hemochromatosis", "slc40a1 can cause hemochromatosis 4", "cause hemochromatosis 4 hfe4", "4 hfe4 mim:606069", "mim:606069 a disorder", "606069 a disorder", "a disorder of iron metabolism", "disorder of iron metabolism characterised", "of iron metabolism characterised by", "iron metabolism characterised by iron", "metabolism characterised by iron overload.", "characterised by iron overload. excess", "by iron overload. excess iron", "iron overload. excess iron is", "overload. excess iron is deposited", "excess iron is deposited in", "iron is deposited in a", "is deposited in a variety", "deposited in a variety of", "in a variety of organs", "a variety of organs leading", "variety of organs leading to", "of organs leading to their", "organs leading to their failure", "to their failure resulting", "their failure resulting in", "failure resulting in serious", "resulting in serious illnesses including", "in serious illnesses including cirrhosis", "illnesses including cirrhosis hepatomas", "cirrhosis hepatomas diabetes", "hepatomas diabetes cardiomyopathy", "diabetes cardiomyopathy arthritis", "cardiomyopathy arthritis and hypogonadotropic", "arthritis and hypogonadotropic hypogonadism. severe", "and hypogonadotropic hypogonadism. severe effects", "hypogonadotropic hypogonadism. severe effects of", "hypogonadism. severe effects of the", "severe effects of the disease", "effects of the disease don't", "of the disease don't usually", "the disease don't usually appear", "disease don't usually appear until", "don't usually appear until after", "usually appear until after decades", "appear until after decades of", "until after decades of progressive", "after decades of progressive iron", "decades of progressive iron overloading", "progressive iron overloading de", "iron overloading de domenico", "overloading de domenico et", "de domenico et al. 2005", "et al. 2005 2006", "2005 2006 2011", "2006 2011 kaplan", "2011 kaplan et al.", "kaplan et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1023", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619053", "r hsa", "hsa 5619053", "r hsa 5619053" ] }, { "record_id": "GLY_000594_1_1023", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc22a5", "slc22a5 causes", "causes systemic", "systemic primary", "primary carnitine", "carnitine deficiency", "defective slc22a5 causes", "slc22a5 causes systemic", "causes systemic primary", "systemic primary carnitine", "primary carnitine deficiency", "deficiency cdsp", "defective slc22a5 causes systemic", "slc22a5 causes systemic primary", "causes systemic primary carnitine", "systemic primary carnitine deficiency", "carnitine deficiency cdsp", "defective slc22a5 causes systemic primary", "slc22a5 causes systemic primary carnitine", "causes systemic primary carnitine deficiency", "primary carnitine deficiency cdsp", "the human", "human slc22a5", "slc22a5 15", "15 and", "and 16", "16 genes", "genes encode", "encode for", "for sodium", "sodium dependent", "high affinity", "affinity carnitine", "carnitine cotransporters", "cotransporters which", "which maintain", "maintain systemic", "systemic and", "and tissue", "tissue concentrations", "concentrations of", "of carnitine.", "carnitine. carnitine", "carnitine is", "is essential", "essential for", "for beta", "beta oxidation", "oxidation of", "of long", "long chain", "chain fatty", "fatty acids", "acids to", "to produce", "produce atp.", "atp. slc22a5", "slc22a5 encodes", "encodes the", "the organic", "organic cation/carnitine", "cation/carnitine transporter", "transporter 2", "octn2 .", "slc22a5 is", "is strongly", "strongly expressed", "expressed in", "in the", "the kidney", "skeletal muscle", "heart and", "and placenta.", "placenta. defects", "defects in", "in slc22a5", "slc22a5 are", "are the", "the cause", "cause of", "of systemic", "an autosomal", "autosomal recessive", "recessive disorder", "disorder of", "of fatty", "fatty acid", "acid oxidation", "oxidation caused", "caused by", "by defective", "defective carnitine", "carnitine transport", "transport resulting", "resulting in", "in cardiac", "or metabolic", "metabolic symptoms.", "symptoms. if", "if diagnosed", "diagnosed early", "all clinical", "clinical symptoms", "symptoms can", "can be", "be completely", "completely reversed", "reversed with", "with a", "a carnitine", "carnitine supplement.", "supplement. however", "if left", "left untreated", "patients will", "will develop", "develop lethal", "lethal heart", "heart failure", "shibbani et", "et al.", "al. 2014", "tamai 2013", "2013 .", "the human slc22a5", "human slc22a5 15", "slc22a5 15 and", "15 and 16", "and 16 genes", "16 genes encode", "genes encode for", "encode for sodium", "for sodium dependent", "dependent high", "high affinity carnitine", "affinity carnitine cotransporters", "carnitine cotransporters 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the", "are the cause", "the cause of", "cause of systemic", "of systemic primary", "cdsp mim:212140", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder of", "disorder of fatty", "of fatty acid", "fatty acid oxidation", "acid oxidation caused", "oxidation caused by", "caused by defective", "by defective carnitine", "defective carnitine transport", "carnitine transport resulting", "transport resulting in", "resulting in cardiac", "cardiac skeletal", "skeletal or", "or metabolic symptoms.", "metabolic symptoms. if", "symptoms. if diagnosed", "if diagnosed early", "early all", "all clinical symptoms", "clinical symptoms can", "symptoms can be", "can be completely", "be completely reversed", "completely reversed with", "reversed with a", "with a carnitine", "a carnitine supplement.", "carnitine supplement. however", "however if", "if left untreated", "untreated patients", "patients will develop", "will develop lethal", "develop lethal heart", "lethal heart failure", "failure shibbani", "shibbani et al.", "et al. 2014", "2014 tamai", "tamai 2013 .", "the human slc22a5 15", "human slc22a5 15 and", "slc22a5 15 and 16", "15 and 16 genes", "and 16 genes encode", "16 genes encode for", "genes encode for sodium", "encode for sodium dependent", "sodium dependent high", "dependent high affinity", "high affinity carnitine cotransporters", "affinity carnitine cotransporters which", "carnitine cotransporters which maintain", "cotransporters which maintain systemic", "which maintain systemic and", "maintain systemic and tissue", "systemic and tissue concentrations", "and tissue concentrations of", "tissue concentrations of carnitine.", "concentrations of carnitine. carnitine", "of carnitine. carnitine is", "carnitine. carnitine is essential", "carnitine is essential for", "is essential for beta", "essential for beta oxidation", "for beta oxidation of", "beta oxidation of long", "oxidation of long chain", "of long chain fatty", "long chain fatty acids", "chain fatty acids to", "fatty acids to produce", "acids to produce atp.", "to produce atp. slc22a5", "produce atp. slc22a5 encodes", "atp. slc22a5 encodes the", "slc22a5 encodes the organic", "encodes the organic cation/carnitine", "the organic cation/carnitine transporter", "organic cation/carnitine transporter 2", "transporter 2 octn2", "2 octn2 .", "octn2 . slc22a5", ". slc22a5 is", "slc22a5 is strongly expressed", "is strongly expressed in", "strongly expressed in the", "expressed in the kidney", "the kidney skeletal", "kidney skeletal muscle", "skeletal muscle heart", "muscle heart and", "heart and placenta. defects", "and placenta. defects in", "placenta. defects in slc22a5", "defects in slc22a5 are", "in slc22a5 are the", "slc22a5 are the cause", "are the cause of", "the cause of systemic", "cause of systemic primary", "of systemic primary carnitine", "mim:212140 an", "212140 an", "an autosomal recessive disorder", "autosomal recessive disorder of", "recessive disorder of fatty", "disorder of fatty acid", "of fatty acid oxidation", "fatty acid oxidation caused", "acid oxidation caused by", "oxidation caused by defective", "caused by defective carnitine", "by defective carnitine transport", "defective carnitine transport resulting", "carnitine transport resulting in", "transport resulting in cardiac", "in cardiac skeletal", "skeletal or metabolic", "or metabolic symptoms. if", "metabolic symptoms. if diagnosed", "symptoms. if diagnosed early", "diagnosed early all", "early all clinical", "all clinical symptoms can", "clinical symptoms can be", "symptoms can be completely", "can be completely reversed", "be completely reversed with", "completely reversed with a", "reversed with a carnitine", "with a carnitine supplement.", "a carnitine supplement. however", "supplement. however if", "however if left", "left untreated patients", "untreated patients will", "patients will develop lethal", "will develop lethal heart", "develop lethal heart failure", "heart failure shibbani", "failure shibbani et", "shibbani et al. 2014", "al. 2014 tamai", "2014 tamai 2013", "the human slc22a5 15 and", "human slc22a5 15 and 16", "slc22a5 15 and 16 genes", "15 and 16 genes encode", "and 16 genes encode for", "16 genes encode for sodium", "genes encode for sodium dependent", "for sodium dependent high", "sodium dependent high affinity", "dependent high affinity carnitine", "high affinity carnitine cotransporters which", "affinity carnitine cotransporters which maintain", "carnitine cotransporters which maintain systemic", "cotransporters which maintain systemic and", "which maintain systemic and tissue", "maintain systemic and tissue concentrations", "systemic and tissue concentrations of", "and tissue concentrations of carnitine.", "tissue concentrations of carnitine. carnitine", "concentrations of carnitine. carnitine is", "of carnitine. carnitine is essential", "carnitine. carnitine is essential for", "carnitine is essential for beta", "is essential for beta oxidation", "essential for beta oxidation of", "for beta oxidation of long", "beta oxidation of long chain", "oxidation of long chain fatty", "of long chain fatty acids", "long chain fatty acids to", "chain fatty acids to produce", "fatty acids to produce atp.", "acids to produce atp. slc22a5", "to produce atp. slc22a5 encodes", "produce atp. slc22a5 encodes the", "atp. slc22a5 encodes the organic", "slc22a5 encodes the organic cation/carnitine", "encodes the organic cation/carnitine transporter", "the organic cation/carnitine transporter 2", "cation/carnitine transporter 2 octn2", "transporter 2 octn2 .", "octn2 . slc22a5 is", ". slc22a5 is strongly", "slc22a5 is strongly expressed in", "is strongly expressed in the", "strongly expressed in the kidney", "in the kidney skeletal", "the kidney skeletal muscle", "skeletal muscle heart and", "muscle heart and placenta.", "heart and placenta. defects in", "and placenta. defects in slc22a5", "placenta. defects in slc22a5 are", "defects in slc22a5 are the", "in slc22a5 are the cause", "slc22a5 are the cause of", "are the cause of systemic", "the cause of systemic primary", "cause of systemic primary carnitine", "of systemic primary carnitine deficiency", "deficiency cdsp mim:212140", "mim:212140 an autosomal", "212140 an autosomal", "an autosomal recessive disorder of", "autosomal recessive disorder of fatty", "recessive disorder of fatty acid", "disorder of fatty acid oxidation", "of fatty acid oxidation caused", "fatty acid oxidation caused by", "acid oxidation caused by defective", "oxidation caused by defective carnitine", "caused by defective carnitine transport", "by defective carnitine transport resulting", "defective carnitine transport resulting in", "carnitine transport resulting in cardiac", "resulting in cardiac skeletal", "cardiac skeletal or", "skeletal or metabolic symptoms.", "or metabolic symptoms. if diagnosed", "metabolic symptoms. if diagnosed early", "if diagnosed early all", "diagnosed early all clinical", "early all clinical symptoms", "all clinical symptoms can be", "clinical symptoms can be completely", "symptoms can be completely reversed", "can be completely reversed with", "be completely reversed with a", "completely reversed with a carnitine", "reversed with a carnitine supplement.", "with a carnitine supplement. however", "carnitine supplement. however if", "supplement. however if left", "however if left untreated", "if left untreated patients", "left untreated patients will", "untreated patients will develop", "patients will develop lethal heart", "will develop lethal heart failure", "lethal heart failure shibbani", "heart failure shibbani et", "failure shibbani et al.", "et al. 2014 tamai", "al. 2014 tamai 2013", "2014 tamai 2013 ." ] }, { "record_id": "GLY_000594_1_1024", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619060", "r hsa", "hsa 5619060", "r hsa 5619060" ] }, { "record_id": "GLY_000594_1_1024", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cp", "cp causes", "causes aceruloplasminemia", "defective cp causes", "cp causes aceruloplasminemia", "aceruloplasminemia acerulop", "defective cp causes aceruloplasminemia", "causes aceruloplasminemia acerulop", "cp causes aceruloplasminemia acerulop", "synthesised in", "in the", "the liver", "liver and", "and secreted", "secreted into", "into plasma", "is a", "a copper", "copper binding", "6 7", "7 atoms", "atoms per", "per molecule", "glycoprotein involved", "involved in", "in iron", "iron trafficking", "trafficking in", "in vertebrates.", "vertebrates. cp", "cp is", "is essential", "essential for", "for slc40a1", "stability at", "at the", "the cell", "cell surface", "the protein", "protein that", "that mediates", "mediates iron", "iron efflux", "efflux from", "from cells.", "cells. cp", "cp also", "also possesses", "possesses ferroxidase", "ferroxidase activity", "which oxidises", "oxidises ferrous", "ferrous iron", "to ferric", "ferric iron", "following its", "its transfer", "transfer out", "out of", "of the", "the cell.", "cell. fe3+", "fe3+ can", "can then", "then be", "be loaded", "loaded on", "on to", "to extracellular", "extracellular transferrin", "transferrin which", "which transports", "transports it", "it around", "around the", "the body", "body to", "to sites", "sites where", "where it", "it is", "is required.", "required. iron", "iron is", "is vital", "vital for", "for many", "many metabolic", "metabolic processes", "processes such", "such as", "as electron", "electron transport", "transport and", "and the", "the transport", "and storage", "storage of", "of oxygen.

              defects", "oxygen.

              defects in", "in cp", "or indeed", "indeed slc40a1", "can lead", "lead to", "to the", "the phenotype", "phenotype of", "of iron", "iron overload", "overload as", "as seen", "seen in", "the disorder", "disorder aceruloplasminemia", "mim:604290 .", "604290 .", ". it", "a rare", "rare autosomal", "autosomal recessive", "recessive disorder", "disorder of", "iron metabolism", "metabolism characterised", "characterised by", "by iron", "iron accumulation", "accumulation mainly", "mainly in", "the brain", "but also", "also in", "in liver", "pancreas and", "and retina.", "retina. patients", "patients develop", "develop retinal", "retinal degeneration", "diabetes mellitus", "mellitus and", "and neurological", "neurological disturbance.", "disturbance. acerulop", "acerulop belongs", "belongs to", "to a", "a group", "group of", "of disorders", "disorders known", "known as", "as nbia", "neurodegeneration with", "with brain", "brain iron", "distinguishing it", "it from", "from hereditary", "hereditary hemochromatosis", "serum iron", "is high", "high but", "but the", "brain is", "is usually", "usually not", "not affected", "and from", "from disorders", "disorders of", "of copper", "copper metabolism", "metabolism such", "as menkes", "menkes and", "and wilson", "wilson disease", "harris et", "et al.", "al. 1995", "kono 2012", "musci et", "al. 2014", "2014 .", "ceruloplasmin cp", "synthesised in the", "in the liver", "the liver and", "liver and secreted", "and secreted into", "secreted into plasma", "plasma is", "is a copper", "a copper binding", "binding 6", "6 7 atoms", "7 atoms per", "atoms per molecule", "molecule glycoprotein", "glycoprotein involved in", "involved in iron", "in iron trafficking", "iron trafficking in", "trafficking in vertebrates.", "in vertebrates. cp", "vertebrates. cp is", "cp is essential", "is essential for", "essential for slc40a1", "slc40a1 ferroportin", "ferroportin stability", "stability at the", "at the cell", "the cell surface", "surface the", "the protein that", "protein that mediates", "that mediates iron", "mediates iron efflux", "iron efflux from", "efflux from cells.", "from cells. cp", "cells. cp also", "cp also possesses", "also possesses ferroxidase", "possesses ferroxidase activity", "activity which", "which oxidises ferrous", "oxidises ferrous iron", "iron fe2+", "fe2+ to", "to ferric iron", "iron fe3+", "fe3+ following", "following its transfer", "its transfer out", "transfer out of", "out of the", "of the cell.", "the cell. fe3+", "cell. fe3+ can", "fe3+ can then", "can then be", "then be loaded", "be loaded on", "loaded on to", "on to extracellular", "to extracellular transferrin", "extracellular transferrin which", "transferrin which transports", "which transports it", "transports it around", "it around the", "around the body", "the body to", "body to sites", "to sites where", "sites where it", "where it is", "it is required.", "is required. iron", "required. iron is", "iron is vital", "is vital for", "vital for many", "for many metabolic", "many metabolic processes", "metabolic processes such", "processes such as", "such as electron", "as electron transport", "electron transport and", "transport and the", "and the transport", "the transport and", "transport and storage", "and storage of", "storage of oxygen.

              defects", "of oxygen.

              defects in", "oxygen.

              defects in cp", "cp or", "or indeed slc40a1", "slc40a1 can", "can lead to", "lead to the", "to the phenotype", "the phenotype of", "phenotype of iron", "of iron overload", "iron overload as", "overload as seen", "as seen in", "seen in the", "in the disorder", "the disorder aceruloplasminemia", "acerulop mim:604290", "mim:604290 . it", "604290 . it", ". it is", "it is a", "is a rare", "a rare autosomal", "rare autosomal recessive", "autosomal recessive disorder", "recessive disorder of", "disorder of iron", "of iron metabolism", "iron metabolism characterised", "metabolism characterised by", "characterised by iron", "by iron accumulation", "iron accumulation mainly", "accumulation mainly in", "mainly in the", "in the brain", "brain but", "but also in", "also in liver", "liver pancreas", "pancreas and retina.", "and retina. patients", "retina. patients develop", "patients develop retinal", "develop retinal degeneration", "degeneration diabetes", "diabetes mellitus and", "mellitus and neurological", "and neurological disturbance.", "neurological disturbance. acerulop", "disturbance. acerulop belongs", "acerulop belongs to", "belongs to a", "to a group", "a group of", "group of disorders", "of disorders known", "disorders known as", "known as nbia", "nbia neurodegeneration", "neurodegeneration with brain", "with brain iron", "brain iron accumulation", "distinguishing it from", "it from hereditary", "from hereditary hemochromatosis", "hemochromatosis serum", "serum iron is", "iron is high", "is high but", "high but the", "but the brain", "the brain is", "brain is usually", "is usually not", "usually not affected", "affected and", "and from disorders", "from disorders of", "disorders of copper", "of copper metabolism", "copper metabolism such", "metabolism such as", "such as menkes", "as menkes and", "menkes and wilson", "and wilson disease", "disease harris", "harris et al.", "et al. 1995", "1995 kono", "2012 musci", "musci et al.", "et al. 2014", "al. 2014 .", "cp synthesised", "synthesised in the liver", "in the liver and", "the liver and secreted", "liver and secreted into", "and secreted into plasma", "into plasma is", "plasma is a", "is a copper binding", "copper binding 6", "binding 6 7", "6 7 atoms per", "7 atoms per molecule", "per molecule glycoprotein", "molecule glycoprotein involved", "glycoprotein involved in iron", "involved in iron trafficking", "in iron trafficking in", "iron trafficking in vertebrates.", "trafficking in vertebrates. cp", "in vertebrates. cp is", "vertebrates. cp is essential", "cp is essential for", "is essential for slc40a1", "for slc40a1 ferroportin", "ferroportin stability at", "stability at the cell", "at the cell surface", "cell surface the", "surface the protein", "the protein that mediates", "protein that mediates iron", "that mediates iron efflux", "mediates iron efflux from", "iron efflux from cells.", "efflux from cells. cp", "from cells. cp also", "cells. cp also possesses", "cp also possesses ferroxidase", "also possesses ferroxidase activity", "ferroxidase activity which", "activity which oxidises", "which oxidises ferrous iron", "ferrous iron fe2+", "fe2+ to ferric", "ferric iron fe3+", "fe3+ following its", "following its transfer out", "its transfer out of", "transfer out of the", "out of the cell.", "of the cell. fe3+", "the cell. fe3+ can", "cell. fe3+ can then", "fe3+ can then be", "can then be loaded", "then be loaded on", "be loaded on to", "loaded on to extracellular", "on to extracellular transferrin", "to extracellular transferrin which", "extracellular transferrin which transports", "transferrin which transports it", "which transports it around", "transports it around the", "it around the body", "around the body to", "the body to sites", "body to sites where", "to sites where it", "sites where it is", "where it is required.", "it is required. iron", "is required. iron is", "required. iron is vital", "iron is vital for", "is vital for many", "vital for many metabolic", "for many metabolic processes", "many metabolic processes such", "metabolic processes such as", "processes such as electron", "such as electron transport", "as electron transport and", "electron transport and the", "transport and the transport", "and the transport and", "the transport and storage", "transport and storage of", "and storage of oxygen.

              defects", "storage of oxygen.

              defects in", "of oxygen.

              defects in cp", "in cp or", "cp or indeed", "indeed slc40a1 can", "slc40a1 can lead", "can lead to the", "lead to the phenotype", "to the phenotype of", "the phenotype of iron", "phenotype of iron overload", "of iron overload as", "iron overload as seen", "overload as seen in", "as seen in the", "seen in the disorder", "in the disorder aceruloplasminemia", "disorder aceruloplasminemia acerulop", "acerulop mim:604290 .", "mim:604290 . it is", "604290 . it is", ". it is a", "it is a rare", "is a rare autosomal", "a rare autosomal recessive", "rare autosomal recessive disorder", "autosomal recessive disorder of", "recessive disorder of iron", "disorder of iron metabolism", "of iron metabolism characterised", "iron metabolism characterised by", "metabolism characterised by iron", "characterised by iron accumulation", "by iron accumulation mainly", "iron accumulation mainly in", "accumulation mainly in the", "mainly in the brain", "the brain but", "brain but also", "but also in liver", "in liver pancreas", "liver pancreas and", "pancreas and retina. patients", "and retina. patients develop", "retina. patients develop retinal", "patients develop retinal degeneration", "retinal degeneration diabetes", "degeneration diabetes mellitus", "diabetes mellitus and neurological", "mellitus and neurological disturbance.", "and neurological disturbance. acerulop", "neurological disturbance. acerulop belongs", "disturbance. acerulop belongs to", "acerulop belongs to a", "belongs to a group", "to a group of", "a group of disorders", "group of disorders known", "of disorders known as", "disorders known as nbia", "as nbia neurodegeneration", "nbia neurodegeneration with", "neurodegeneration with brain iron", "with brain iron accumulation", "accumulation distinguishing", "distinguishing it from hereditary", "it from hereditary hemochromatosis", "hereditary hemochromatosis serum", "hemochromatosis serum iron", "serum iron is high", "iron is high but", "is high but the", "high but the brain", "but the brain is", "the brain is usually", "brain is usually not", "is usually not affected", "not affected and", "affected and from", "and from disorders of", "from disorders of copper", "disorders of copper metabolism", "of copper metabolism such", "copper metabolism such as", "metabolism such as menkes", "such as menkes and", "as menkes and wilson", "menkes and wilson disease", "wilson disease harris", "disease harris et", "harris et al. 1995", "al. 1995 kono", "1995 kono 2012", "kono 2012 musci", "2012 musci et", "musci et al. 2014", "et al. 2014 .", "cp synthesised in", "synthesised in the liver and", "in the liver and secreted", "the liver and secreted into", "liver and secreted into plasma", "secreted into plasma is", "into plasma is a", "plasma is a copper", "a copper binding 6", "copper binding 6 7", "binding 6 7 atoms", "6 7 atoms per molecule", "atoms per molecule glycoprotein", "per molecule glycoprotein involved", "molecule glycoprotein involved in", "glycoprotein involved in iron trafficking", "involved in iron trafficking in", "in iron trafficking in vertebrates.", "iron trafficking in vertebrates. cp", "trafficking in vertebrates. cp is", "in vertebrates. cp is essential", "vertebrates. cp is essential for", "cp is essential for slc40a1", "essential for slc40a1 ferroportin", "slc40a1 ferroportin stability", "ferroportin stability at the", "stability at the cell surface", "the cell surface the", "cell surface the protein", "surface the protein that", "the protein that mediates iron", "protein that mediates iron efflux", "that mediates iron efflux from", "mediates iron efflux from cells.", "iron efflux from cells. cp", "efflux from cells. cp also", "from cells. cp also possesses", "cells. cp also possesses ferroxidase", "cp also possesses ferroxidase activity", "possesses ferroxidase activity which", "ferroxidase activity which oxidises", "activity which oxidises ferrous", "oxidises ferrous iron fe2+", "iron fe2+ to", "fe2+ to ferric iron", "to ferric iron fe3+", "iron fe3+ following", "fe3+ following its transfer", "following its transfer out of", "its transfer out of the", "transfer out of the cell.", "out of the cell. fe3+", "of the cell. fe3+ can", "the cell. fe3+ can then", "cell. fe3+ can then be", "fe3+ can then be loaded", "can then be loaded on", "then be loaded on to", "be loaded on to extracellular", "loaded on to extracellular transferrin", "on to extracellular transferrin which", "to extracellular transferrin which transports", "extracellular transferrin which transports it", "transferrin which transports it around", "which transports it around the", "transports it around the body", "it around the body to", "around the body to sites", "the body to sites where", "body to sites where it", "to sites where it is", "sites where it is required.", "where it is required. iron", "it is required. iron is", "is required. iron is vital", "required. iron is vital for", "iron is vital for many", "is vital for many metabolic", "vital for many metabolic processes", "for many metabolic processes such", "many metabolic processes such as", "metabolic processes such as electron", "processes such as electron transport", "such as electron transport and", "as electron transport and the", "electron transport and the transport", "transport and the transport and", "and the transport and storage", "the transport and storage of", "transport and storage of oxygen.

              defects", "and storage of oxygen.

              defects in", "storage of oxygen.

              defects in cp", "oxygen.

              defects in cp or", "in cp or indeed", "cp or indeed slc40a1", "or indeed slc40a1 can", "indeed slc40a1 can lead", "slc40a1 can lead to", "can lead to the phenotype", "lead to the phenotype of", "to the phenotype of iron", "the phenotype of iron overload", "phenotype of iron overload as", "of iron overload as seen", "iron overload as seen in", "overload as seen in the", "as seen in the disorder", "seen in the disorder aceruloplasminemia", "the disorder aceruloplasminemia acerulop", "aceruloplasminemia acerulop mim:604290", "acerulop mim:604290 . it", "mim:604290 . it is a", "604290 . it is a", ". it is a rare", "it is a rare autosomal", "is a rare autosomal recessive", "a rare autosomal recessive disorder", "rare autosomal recessive disorder of", "autosomal recessive disorder of iron", "recessive disorder of iron metabolism", "disorder of iron metabolism characterised", "of iron metabolism characterised by", "iron metabolism characterised by iron", "metabolism characterised by iron accumulation", "characterised by iron accumulation mainly", "by iron accumulation mainly in", "iron accumulation mainly in the", "accumulation mainly in the brain", "in the brain but", "the brain but also", "brain but also in", "also in liver pancreas", "in liver pancreas and", "liver pancreas and retina.", "pancreas and retina. patients develop", "and retina. patients develop retinal", "retina. patients develop retinal degeneration", "develop retinal degeneration diabetes", "retinal degeneration diabetes mellitus", "degeneration diabetes mellitus and", "diabetes mellitus and neurological disturbance.", "mellitus and neurological disturbance. acerulop", "and neurological disturbance. acerulop belongs", "neurological disturbance. acerulop belongs to", "disturbance. acerulop belongs to a", "acerulop belongs to a group", "belongs to a group of", "to a group of disorders", "a group of disorders known", "group of disorders known as", "of disorders known as nbia", "known as nbia neurodegeneration", "as nbia neurodegeneration with", "nbia neurodegeneration with brain", "neurodegeneration with brain iron accumulation", "iron accumulation distinguishing", "accumulation distinguishing it", "distinguishing it from hereditary hemochromatosis", "from hereditary hemochromatosis serum", "hereditary hemochromatosis serum iron", "hemochromatosis serum iron is", "serum iron is high but", "iron is high but the", "is high but the brain", "high but the brain is", "but the brain is usually", "the brain is usually not", "brain is usually not affected", "usually not affected and", "not affected and from", "affected and from disorders", "and from disorders of copper", "from disorders of copper metabolism", "disorders of copper metabolism such", "of copper metabolism such as", "copper metabolism such as menkes", "metabolism such as menkes and", "such as menkes and wilson", "as menkes and wilson disease", "and wilson disease harris", "wilson disease harris et", "disease harris et al.", "et al. 1995 kono", "al. 1995 kono 2012", "kono 2012 musci et", "2012 musci et al.", "musci et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1025", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619068", "r hsa", "hsa 5619068", "r hsa 5619068" ] }, { "record_id": "GLY_000594_1_1025", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc2a10", "slc2a10 causes", "causes arterial", "arterial tortuosity", "tortuosity syndrome", "defective slc2a10 causes", "slc2a10 causes arterial", "causes arterial tortuosity", "arterial tortuosity syndrome", "syndrome ats", "defective slc2a10 causes arterial", "slc2a10 causes arterial tortuosity", "causes arterial tortuosity syndrome", "tortuosity syndrome ats", "defective slc2a10 causes arterial tortuosity", "slc2a10 causes arterial tortuosity syndrome", "arterial tortuosity syndrome ats", "four class", "class iii", "iii 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in", "in the", "the hypothalamus.", "hypothalamus. it", "it mediates", "mediates the", "the reabsorption", "reabsorption of", "of water", "water in", "the kidney", "kidney and", "and its", "its synthesis", "synthesis and", "and release", "release are", "are physiologically", "physiologically regulated", "regulated by", "by plasma", "plasma osmolarity", "blood pressure", "pressure and/or", "and/or blood", "blood volume.", "volume. avp", "binds to", "to vasopressin", "vasopressin receptors", "receptors avpr1", "avpr1 and", "and 2", "located on", "on the", "the basolateral", "basolateral surface", "surface of", "kidney collecting", "collecting duct.", "duct. this", "this binding", "binding results", "results in", "in interaction", "interaction of", "of avprs", "avprs with", "with the", "the g", "g protein", "protein alpha", "alpha s.", "s. following", "following a", "a cascade", "cascade of", "of downstream", "downstream events", "ultimately the", "the water", "water channel", "channel 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              mutations", "decreased.

              mutations in", "in avp", "avp make", "make it", "it unavailable", "unavailable to", "to its", "its avprs", "avprs in", "resulting in", "in dysregulation", "dysregulation of", "reabsorption. this", "this can", "can cause", "cause familial", "familial neurohypophyseal", "an autosomal", "autosomal dominant", "dominant disorder", "disorder characterised", "characterised by", "by persistent", "persistent excessive", "excessive thirst", "thirst resulting", "in constant", "constant drinking", "and passage", "passage of", "of large", "large volumes", "volumes of", "of urine", "polyuria .", ". in", "in fndi", "the production", "production and", "release of", "avp from", "from the", "the posterior", "posterior pituitary", "pituitary gland", "gland is", "is impaired", "moeller et", "et al.", "al. 2013", "2013 .", "vasopressin avp", "avp 20 28", "is a 9", "a 9 amino", "9 amino acid", "amino acid long", "acid long signal", "long signal peptide", "signal peptide produced", "peptide produced by", "produced by cleavage", "by cleavage of", "cleavage of the", "of the precursor", "the precursor protein", "precursor protein avp", "protein avp in", "avp in the", "in the hypothalamus.", "the hypothalamus. it", "hypothalamus. it mediates", "it mediates the", "mediates the reabsorption", "the reabsorption of", "reabsorption of water", "of water in", "water in the", "in the kidney", "the kidney and", "kidney and its", "and its synthesis", "its synthesis and", "synthesis and release", "and release are", "release are physiologically", "are physiologically regulated", "physiologically regulated by", "regulated by plasma", "by plasma osmolarity", "osmolarity blood", "blood pressure and/or", "pressure and/or blood", "and/or blood volume.", "blood volume. avp", "volume. avp 20", "28 binds", "binds to vasopressin", "to vasopressin receptors", "vasopressin receptors avpr1", "receptors avpr1 and", "avpr1 and 2", "2 located", "located on the", "on the basolateral", "the basolateral surface", "basolateral surface of", "surface of the", "of the kidney", "the kidney collecting", "kidney collecting duct.", "collecting duct. this", "duct. this binding", "this binding results", "binding results in", "results in interaction", "in interaction of", "interaction of avprs", "of avprs with", "avprs with the", "with the g", "the g protein", "g protein alpha", "protein alpha s.", "alpha s. following", "s. following a", "following a cascade", "a cascade of", "cascade of downstream", "of downstream events", "events ultimately", "ultimately the water", "the water channel", "water channel aquaporin", "channel aquaporin 2", "2 aqp2", "aqp2 translocates", "translocates from intracellular", "from intracellular stores", "intracellular stores to", "stores to the", "to the apical", "the apical surface", "apical surface where", "surface where it", "where it functions", "it functions as", "functions as the", "as the entry", "the entry site", "entry site for", "site for water", "for water reabsorption.", "water reabsorption. when", "reabsorption. when water", "when water balance", "water balance is", "balance is achieved", "achieved plasma", "plasma levels of", "levels of avp", "of avp 20", "28 drop", "drop and aqp2", "and aqp2 levels", "aqp2 levels in", "levels in the", "in the apical", "the apical plasma", "apical plasma membrane", "plasma membrane are", "membrane are decreased.

              mutations", "are decreased.

              mutations in", "decreased.

              mutations in avp", "in avp make", "avp make it", "make it unavailable", "it unavailable to", "unavailable to its", "to its avprs", "its avprs in", "avprs in the", "kidney resulting", "resulting in dysregulation", "in dysregulation of", "dysregulation of water", "of water reabsorption.", "water reabsorption. this", "reabsorption. this can", "this can cause", "can cause familial", "cause familial neurohypophyseal", "familial neurohypophyseal diabetes", "insipidus fndi", "an autosomal dominant", "autosomal dominant disorder", "dominant disorder characterised", "disorder characterised by", "characterised by persistent", "by persistent excessive", "persistent excessive thirst", "excessive thirst resulting", "thirst resulting in", "resulting in constant", "in constant drinking", "drinking polydipsia", "polydipsia and", "and passage of", "passage of large", "of large volumes", "large volumes of", "volumes of urine", "urine polyuria", "polyuria . in", ". in fndi", "fndi the", "the production and", "production and release", "and release of", "release of avp", "of avp from", "avp from the", "from the posterior", "the posterior pituitary", "posterior pituitary gland", "pituitary gland is", "gland is impaired", "impaired moeller", "moeller et al.", "et al. 2013", "al. 2013 .", "arginine vasopressin avp", "vasopressin avp 20", "28 is", "is a 9 amino", "a 9 amino acid", "9 amino acid long", "amino acid long signal", "acid long signal peptide", "long signal peptide produced", "signal peptide produced by", "peptide produced by cleavage", "produced by cleavage of", "by cleavage of the", "cleavage of the precursor", "of the precursor protein", "the precursor protein avp", "precursor protein avp in", "protein avp in the", "avp in the hypothalamus.", "in the hypothalamus. it", "the hypothalamus. it mediates", "hypothalamus. it mediates the", "it mediates the reabsorption", "mediates the reabsorption of", "the reabsorption of water", "reabsorption of water in", "of water in the", "water in the kidney", "in the kidney and", "the kidney and its", "kidney and its synthesis", "and its synthesis and", "its synthesis and release", "synthesis and release are", "and release are physiologically", "release are physiologically regulated", "are physiologically regulated by", "physiologically regulated by plasma", "regulated by plasma osmolarity", "plasma osmolarity blood", "osmolarity blood pressure", "blood pressure and/or blood", "pressure and/or blood volume.", "and/or blood volume. avp", "blood volume. avp 20", "volume. avp 20 28", "20 28 binds", "28 binds to", "binds to vasopressin receptors", "to vasopressin receptors avpr1", "vasopressin receptors avpr1 and", "receptors avpr1 and 2", "and 2 located", "2 located on", "located on the basolateral", "on the basolateral surface", "the basolateral surface of", "basolateral surface of the", "surface of the kidney", "of the kidney collecting", "the kidney collecting duct.", "kidney collecting duct. this", "collecting duct. this binding", "duct. this binding results", "this binding results in", "binding results in interaction", "results in interaction of", "in interaction of avprs", "interaction of avprs with", "of avprs with the", "avprs with the g", "with the g protein", "the g protein alpha", "g protein alpha s.", "protein alpha s. following", "alpha s. following a", "s. following a cascade", "following a cascade of", "a cascade of downstream", "cascade of downstream events", "downstream events ultimately", "events ultimately the", "ultimately the water channel", "the water channel aquaporin", "water channel aquaporin 2", "aquaporin 2 aqp2", "aqp2 translocates from", "translocates from intracellular stores", "from intracellular stores to", "intracellular stores to the", "stores to the apical", "to the apical surface", "the apical surface where", "apical surface where it", "surface where it functions", "where it functions as", "it functions as the", "functions as the entry", "as the entry site", "the entry site for", "entry site for water", "site for water reabsorption.", "for water reabsorption. when", "water reabsorption. when water", "reabsorption. when water balance", "when water balance is", "water balance is achieved", "is achieved plasma", "achieved plasma levels", "plasma levels of avp", "levels of avp 20", "of avp 20 28", "20 28 drop", "28 drop and", "drop and aqp2 levels", "and aqp2 levels in", "aqp2 levels in the", "levels in the apical", "in the apical plasma", "the apical plasma membrane", "apical plasma membrane are", "plasma membrane are decreased.

              mutations", "membrane are decreased.

              mutations in", "are decreased.

              mutations in avp", "decreased.

              mutations in avp make", "in avp make it", "avp make it unavailable", "make it unavailable to", "it unavailable to its", "unavailable to its avprs", "to its avprs in", "its avprs in the", "avprs in the kidney", "the kidney resulting", "kidney resulting in", "resulting in dysregulation of", "in dysregulation of water", "dysregulation of water reabsorption.", "of water reabsorption. this", "water reabsorption. this can", "reabsorption. this can cause", "this can cause familial", "can cause familial neurohypophyseal", "cause familial neurohypophyseal diabetes", "familial neurohypophyseal diabetes insipidus", "diabetes insipidus fndi", "fndi an", "an autosomal dominant disorder", "autosomal dominant disorder characterised", "dominant disorder characterised by", "disorder characterised by persistent", "characterised by persistent excessive", "by persistent excessive thirst", "persistent excessive thirst resulting", "excessive thirst resulting in", "thirst resulting in constant", "resulting in constant drinking", "constant drinking polydipsia", "polydipsia and passage", "and passage of large", "passage of large volumes", "of large volumes of", "large volumes of urine", "of urine polyuria", "urine polyuria .", "polyuria . in fndi", "in fndi the", "fndi the production", "the production and release", "production and release of", "and release of avp", "release of avp from", "of avp from the", "avp from the posterior", "from the posterior pituitary", "the posterior pituitary gland", "posterior pituitary gland is", "pituitary gland is impaired", "is impaired moeller", "impaired moeller et", "moeller et al. 2013", "et al. 2013 .", "arginine vasopressin avp 20", "vasopressin avp 20 28", "20 28 is", "28 is a", "is a 9 amino acid", "a 9 amino acid long", "9 amino acid long signal", "amino acid long signal peptide", "acid long signal peptide produced", "long signal peptide produced by", "signal peptide produced by cleavage", "peptide produced by cleavage of", "produced by cleavage of the", "by cleavage of the precursor", "cleavage of the precursor protein", "of the precursor protein avp", "the precursor protein avp in", "precursor protein avp in the", "protein avp in the hypothalamus.", "avp in the hypothalamus. it", "in the hypothalamus. it mediates", "the hypothalamus. it mediates the", "hypothalamus. it mediates the reabsorption", "it mediates the reabsorption of", "mediates the reabsorption of water", "the reabsorption of water in", "reabsorption of water in the", "of water in the kidney", "water in the kidney and", "in the kidney and its", "the kidney and its synthesis", "kidney and its synthesis and", "and its synthesis and release", "its synthesis and release are", "synthesis and release are physiologically", "and release are physiologically regulated", "release are physiologically regulated by", "are physiologically regulated by plasma", "physiologically regulated by plasma osmolarity", "by plasma osmolarity blood", "plasma osmolarity blood pressure", "osmolarity blood pressure and/or", "blood pressure and/or blood volume.", "pressure and/or blood volume. avp", "and/or blood volume. avp 20", "blood volume. avp 20 28", "avp 20 28 binds", "20 28 binds to", "28 binds to vasopressin", "binds to vasopressin receptors avpr1", "to vasopressin receptors avpr1 and", "vasopressin receptors avpr1 and 2", "avpr1 and 2 located", "and 2 located on", "2 located on the", "located on the basolateral surface", "on the basolateral surface of", "the basolateral surface of the", "basolateral surface of the kidney", "surface of the kidney collecting", "of the kidney collecting duct.", "the kidney collecting duct. this", "kidney collecting duct. this binding", "collecting duct. this binding results", "duct. this binding results in", "this binding results in interaction", "binding results in interaction of", "results in interaction of avprs", "in interaction of avprs with", "interaction of avprs with the", "of avprs with the g", "avprs with the g protein", "with the g protein alpha", "the g protein alpha s.", "g protein alpha s. following", "protein alpha s. following a", "alpha s. following a cascade", "s. following a cascade of", "following a cascade of downstream", "a cascade of downstream events", "of downstream events ultimately", "downstream events ultimately the", "events ultimately the water", "ultimately the water channel aquaporin", "the water channel aquaporin 2", "channel aquaporin 2 aqp2", "2 aqp2 translocates", "aqp2 translocates from intracellular", "translocates from intracellular stores to", "from intracellular stores to the", "intracellular stores to the apical", "stores to the apical surface", "to the apical surface where", "the apical surface where it", "apical surface where it functions", "surface where it functions as", "where it functions as the", "it functions as the entry", "functions as the entry site", "as the entry site for", "the entry site for water", "entry site for water reabsorption.", "site for water reabsorption. when", "for water reabsorption. when water", "water reabsorption. when water balance", "reabsorption. when water balance is", "when water balance is achieved", "balance is achieved plasma", "is achieved plasma levels", "achieved plasma levels of", "plasma levels of avp 20", "levels of avp 20 28", "avp 20 28 drop", "20 28 drop and", "28 drop and aqp2", "drop and aqp2 levels in", "and aqp2 levels in the", "aqp2 levels in the apical", "levels in the apical plasma", "in the apical plasma membrane", "the apical plasma membrane are", "apical plasma membrane are decreased.

              mutations", "plasma membrane are decreased.

              mutations in", "membrane are decreased.

              mutations in avp", "are decreased.

              mutations in avp make", "decreased.

              mutations in avp make it", "in avp make it unavailable", "avp make it unavailable to", "make it unavailable to its", "it unavailable to its avprs", "unavailable to its avprs in", "to its avprs in the", "its avprs in the kidney", "in the kidney resulting", "the kidney resulting in", "kidney resulting in dysregulation", "resulting in dysregulation of water", "in dysregulation of water reabsorption.", "dysregulation of water reabsorption. this", "of water reabsorption. this can", "water reabsorption. this can cause", "reabsorption. this can cause familial", "this can cause familial neurohypophyseal", "can cause familial neurohypophyseal diabetes", "cause familial neurohypophyseal diabetes insipidus", "neurohypophyseal diabetes insipidus fndi", "fndi an autosomal", "an autosomal dominant disorder characterised", "autosomal dominant disorder characterised by", "dominant disorder characterised by persistent", "disorder characterised by persistent excessive", "characterised by persistent excessive thirst", "by persistent excessive thirst resulting", "persistent excessive thirst resulting in", "excessive thirst resulting in constant", "thirst resulting in constant drinking", "in constant drinking polydipsia", "drinking polydipsia and", "polydipsia and passage of", "and passage of large volumes", "passage of large volumes of", "of large volumes of urine", "volumes of urine polyuria", "of urine polyuria .", "urine polyuria . in", ". in fndi the", "in fndi the production", "fndi the production and", "the production and release of", "production and release of avp", "and release of avp from", "release of avp from the", "of avp from the posterior", "avp from the posterior pituitary", "from the posterior pituitary gland", "the posterior pituitary gland is", "posterior pituitary gland is impaired", "gland is impaired moeller", "is impaired moeller et", "impaired moeller et al.", "moeller et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1028", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5621575", "r hsa", "hsa 5621575", "r hsa 5621575" ] }, { "record_id": "GLY_000594_1_1028", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dc sign", "cd209 dc", "sign signaling", "cd209 dc sign", "dc sign signaling", "also called", "called as", "as dc", "dc specific", "specific intracellular", "intracellular adhesion", "adhesion molecule", "molecule 3", "3 grabbing", "grabbing non", "non integrin", "is a", "a type", "type ii", "ii transmembrane", "transmembrane c", "c type", "type lectin", "lectin receptor", "receptor preferentially", "preferentially expressed", "expressed on", "on dendritic", "dendritic cells", "dcs .", ". cd209", "cd209 functions", "functions as", "as a", "a pattern", "pattern recognition", "recognition receptor", "that recognises", "recognises several", "several microorganisms", "microorganisms and", "and pathogens", "contributing to", "to generation", "generation of", "of pathogen", "pathogen tailored", "tailored immune", "immune responses", "gringhuis &", "& geijtenbeek", "geijtenbeek 2010", "den dunnen", "dunnen et", "et al.", "al. 2009", "svajger et", "al. 2010", "2010 .", "cd209 interacts", "interacts with", "with different", "different mannose", "mannose expressing", "expressing pathogens", "pathogens such", "such as", "as mycobacterium", "mycobacterium tuberculosis", "tuberculosis and", "and hiv", "hiv 1", "gringhuis et", "al. 2007", "geijtenbeek et", "al. 2000a", "2000a .", ". it", "it also", "also acts", "acts as", "as an", "an adhesion", "adhesion receptor", "receptor that", "that interacts", "with icam2", "molecule 2", "on endothelial", "endothelial cells", "cells and", "and icam3", "icam3 on", "on t", "t cells", "al. 2000b", "2000b c", "c .", "functions not", "not only", "only as", "an independent", "independent prr", "but is", "is also", "also implicated", "implicated in", "in the", "the modulation", "modulation of", "of toll", "toll like", "like receptor", "signaling at", "at the", "the level", "level of", "of the", "the transcription", "transcription factor", "factor nf", "nf kb", "2009 .", ". clec7a", "dectin 1", "and cd209", "signalling modulates", "modulates toll", "signalling through", "through the", "the kinase", "kinase raf1", "raf1 that", "that is", "is independent", "independent of", "the syk", "syk pathway", "pathway but", "but integrated", "integrated with", "with it", "it at", "of nf", "kb activation.", "activation. the", "the activation", "activation of", "of raf1", "raf1 by", "by clec7a", "clec7a or", "or cd209", "cd209 does", "does not", "not lead", "lead to", "to activation", "of extracellular", "extracellular signal", "signal regulated", "regulated kinase", "kinase 1", "erk1 /2", "/2 or", "or mitogen", "mitogen activated", "activated protein", "protein kinase", "kinase kinase", "mek1 /2", "/2 but", "but leads", "leads to", "to the", "the phosphorylation", "phosphorylation and", "and subsequent", "subsequent acetylation", "acetylation of", "of rela", "p65 .", ". rela", "rela phosphorylated", "phosphorylated on", "on s276", "s276 not", "only positively", "positively regulates", "regulates the", "the activity", "activity of", "of p65", "p65 through", "through acetylation", "but also", "also represses", "represses relb", "relb activity", "activity by", "by sequestering", "sequestering active", "active relb", "relb into", "into inactive", "inactive p65", "p65 relb", "relb dimers", "dimers that", "that do", "do not", "not bind", "bind dna", "jacque et", "al. 2005", "2005 .", ". raf1", "raf1 dependent", "dependent signaling", "signaling pathway", "pathway is", "is crucial", "crucial in", "in dectin", "1 mediated", "mediated immunity", "immunity as", "as it", "it modulates", "modulates both", "both the", "the canonical", "promoting p65", "p65 phosphorylation", "and acetylation", "and non", "non canonical", "forming inactive", "nk kb", "cd209 also", "also called as", "called as dc", "as dc sign", "sign dc", "dc specific intracellular", "specific intracellular adhesion", "intracellular adhesion molecule", "adhesion molecule 3", "molecule 3 grabbing", "3 grabbing non", "grabbing non integrin", "is a type", "a type ii", "type ii transmembrane", "ii transmembrane c", "transmembrane c type", "c type lectin", "type lectin receptor", "lectin receptor preferentially", "receptor preferentially expressed", "preferentially expressed on", "expressed on dendritic", "on dendritic cells", "cells dcs", "dcs . cd209", ". cd209 functions", "cd209 functions as", "functions as a", "as a pattern", "a pattern recognition", "pattern recognition receptor", "receptor prr", "prr that", "that recognises several", "recognises several microorganisms", "several microorganisms and", "microorganisms and pathogens", "pathogens contributing", "contributing to generation", "to generation of", "generation of pathogen", "of pathogen tailored", "pathogen tailored immune", "tailored immune responses", "responses gringhuis", "gringhuis & geijtenbeek", "& geijtenbeek 2010", "2010 den", "den dunnen et", "dunnen et al.", "et al. 2009", "2009 svajger", "svajger et al.", "et al. 2010", "al. 2010 .", "2010 . cd209", ". cd209 interacts", "cd209 interacts with", "interacts with different", "with different mannose", "different mannose expressing", "mannose expressing pathogens", "expressing pathogens such", "pathogens such as", "such as mycobacterium", "as mycobacterium tuberculosis", "mycobacterium tuberculosis and", "tuberculosis and hiv", "and hiv 1", "1 gringhuis", "gringhuis et al.", "et al. 2007", "2007 geijtenbeek", "geijtenbeek et al.", "et al. 2000a", "al. 2000a .", "2000a . it", ". it also", "it also acts", "also acts as", "acts as an", "as an adhesion", "an adhesion receptor", "adhesion receptor that", "receptor that interacts", "that interacts with", "interacts with icam2", "icam2 intracellular", "adhesion molecule 2", "2 on", "on endothelial cells", "endothelial cells and", "cells and icam3", "and icam3 on", "icam3 on t", "on t cells", "cells geijtenbeek", "et al. 2000b", "al. 2000b c", "2000b c .", "c . cd209", "cd209 functions not", "functions not only", "not only as", "only as an", "as an independent", "an independent prr", "prr but", "but is also", "is also implicated", "also implicated in", "implicated in the", "in the modulation", "the modulation of", "modulation of toll", "of toll like", "toll like receptor", "receptor tlr", "tlr signaling", "signaling at the", "at the level", "the level of", "level of the", "of the transcription", "the transcription factor", "transcription factor nf", "factor nf kb", "kb gringhuis", "al. 2009 .", "2009 . clec7a", "clec7a dectin", "1 and", "sign signalling", "signalling modulates toll", "modulates toll like", "tlr signalling", "signalling through the", "through the kinase", "the kinase raf1", "kinase raf1 that", "raf1 that is", "that is independent", "is independent of", "independent of the", "of the syk", "the syk pathway", "syk pathway but", "pathway but integrated", "but integrated with", "integrated with it", "with it at", "it at the", "level of nf", "of nf kb", "nf kb activation.", "kb activation. the", "activation. the activation", "the activation of", "activation of raf1", "of raf1 by", "raf1 by clec7a", "by clec7a or", "clec7a or cd209", "or cd209 does", "cd209 does not", "does not lead", "not lead to", "lead to activation", "to activation of", "activation of extracellular", "of extracellular signal", "extracellular signal regulated", "signal regulated kinase", "regulated kinase 1", "1 erk1", "erk1 /2 or", "/2 or mitogen", "or mitogen activated", "mitogen activated protein", "activated protein kinase", "protein kinase kinase", "kinase kinase 1", "1 mek1", "mek1 /2 but", "/2 but leads", "but leads to", "leads to the", "to the phosphorylation", "the phosphorylation and", "phosphorylation and subsequent", "and subsequent acetylation", "subsequent acetylation of", "acetylation of rela", "rela p65", "p65 . rela", ". rela phosphorylated", "rela phosphorylated on", "phosphorylated on s276", "on s276 not", "s276 not only", "not only positively", "only positively regulates", "positively regulates the", "regulates the activity", "the activity of", "activity of p65", "of p65 through", "p65 through acetylation", "through acetylation of", "acetylation of p65", "p65 but", "but also represses", "also represses relb", "represses relb activity", "relb activity by", "activity by sequestering", "by sequestering active", "sequestering active relb", "active relb into", "relb into inactive", "into inactive p65", "inactive p65 relb", "p65 relb dimers", "relb dimers that", "dimers that do", "that do not", "do not bind", "not bind dna", "dna gringhuis", "2007 svajger", "2010 jacque", "jacque et al.", "et al. 2005", "al. 2005 .", "2005 . raf1", ". raf1 dependent", "raf1 dependent signaling", "dependent signaling pathway", "signaling pathway is", "pathway is crucial", "is crucial in", "crucial in dectin", "in dectin 1", "dectin 1 mediated", "1 mediated immunity", "mediated immunity as", "immunity as it", "as it modulates", "it modulates both", "modulates both the", "both the canonical", "canonical promoting", "promoting p65 phosphorylation", "p65 phosphorylation and", "phosphorylation and acetylation", "acetylation and", "and non canonical", "canonical forming", "forming inactive p65", "dimers nk", "nk kb activation.", "cd209 also called", "also called as dc", "called as dc sign", "dc sign dc", "sign dc specific", "dc specific intracellular adhesion", "specific intracellular adhesion molecule", "intracellular adhesion molecule 3", "adhesion molecule 3 grabbing", "molecule 3 grabbing non", "3 grabbing non integrin", "integrin is", "is a type ii", "a type ii transmembrane", "type ii transmembrane c", "ii transmembrane c type", "transmembrane c type lectin", "c type lectin receptor", "type lectin receptor preferentially", "lectin receptor preferentially expressed", "receptor preferentially expressed on", "preferentially expressed on dendritic", "expressed on dendritic cells", "dendritic cells dcs", "cells dcs .", "dcs . cd209 functions", ". cd209 functions as", "cd209 functions as a", "functions as a pattern", "as a pattern recognition", "a pattern recognition receptor", "recognition receptor prr", "prr that recognises", "that recognises several microorganisms", "recognises several microorganisms and", "several microorganisms and pathogens", "and pathogens contributing", "pathogens contributing to", "contributing to generation of", "to generation of pathogen", "generation of pathogen tailored", "of pathogen tailored immune", "pathogen tailored immune responses", "immune responses gringhuis", "responses gringhuis &", "gringhuis & geijtenbeek 2010", "geijtenbeek 2010 den", "2010 den dunnen", "den dunnen et al.", "dunnen et al. 2009", "al. 2009 svajger", "2009 svajger et", "svajger et al. 2010", "et al. 2010 .", "al. 2010 . cd209", "2010 . cd209 interacts", ". cd209 interacts with", "cd209 interacts with different", "interacts with different mannose", "with different mannose expressing", "different mannose expressing pathogens", "mannose expressing pathogens such", "expressing pathogens such as", "pathogens such as mycobacterium", "such as mycobacterium tuberculosis", "as mycobacterium tuberculosis and", "mycobacterium tuberculosis and hiv", "tuberculosis and hiv 1", "hiv 1 gringhuis", "1 gringhuis et", "gringhuis et al. 2007", "al. 2007 geijtenbeek", "2007 geijtenbeek et", "geijtenbeek et al. 2000a", "et al. 2000a .", "al. 2000a . it", "2000a . it also", ". it also acts", "it also acts as", "also acts as an", "acts as an adhesion", "as an adhesion receptor", "an adhesion receptor that", "adhesion receptor that interacts", "receptor that interacts with", "that interacts with icam2", "with icam2 intracellular", "icam2 intracellular adhesion", "intracellular adhesion molecule 2", "molecule 2 on", "2 on endothelial", "on endothelial cells and", "endothelial cells and icam3", "cells and icam3 on", "and icam3 on t", "icam3 on t cells", "t cells geijtenbeek", "cells geijtenbeek et", "geijtenbeek et al. 2000b", "et al. 2000b c", "al. 2000b c .", "2000b c . cd209", "c . cd209 functions", ". cd209 functions not", "cd209 functions not only", "functions not only as", "not only as an", "only as an independent", "as an independent prr", "independent prr but", "prr but is", "but is also implicated", "is also implicated in", "also implicated in the", "implicated in the modulation", "in the modulation of", "the modulation of toll", "modulation of toll like", "of toll like receptor", "like receptor tlr", "tlr signaling at", "signaling at the level", "at the level of", "the level of the", "level of the transcription", "of the transcription factor", "the transcription factor nf", "transcription factor nf kb", "nf kb gringhuis", "kb gringhuis et", "gringhuis et al. 2009", "et al. 2009 .", "al. 2009 . clec7a", ". clec7a dectin", "clec7a dectin 1", "dectin 1 and", "1 and cd209", "and cd209 dc", "dc sign signalling", "sign signalling modulates", "signalling modulates toll like", "modulates toll like receptor", "tlr signalling through", "signalling through the kinase", "through the kinase raf1", "the kinase raf1 that", "kinase raf1 that is", "raf1 that is independent", "that is independent of", "is independent of the", "independent of the syk", "of the syk pathway", "the syk pathway but", "syk pathway but integrated", "pathway but integrated with", "but integrated with it", "integrated with it at", "with it at the", "it at the level", "the level of nf", "level of nf kb", "of nf kb activation.", "nf kb activation. the", "kb activation. the activation", "activation. the activation of", "the activation of raf1", "activation of raf1 by", "of raf1 by clec7a", "raf1 by clec7a or", "by clec7a or cd209", "clec7a or cd209 does", "or cd209 does not", "cd209 does not lead", "does not lead to", "not lead to activation", "lead to activation of", "to activation of extracellular", "activation of extracellular signal", "of extracellular signal regulated", "extracellular signal regulated kinase", "signal regulated kinase 1", "kinase 1 erk1", "1 erk1 /2", "erk1 /2 or mitogen", "/2 or mitogen activated", "or mitogen activated protein", "mitogen activated protein kinase", "activated protein kinase kinase", "protein kinase kinase 1", "kinase 1 mek1", "1 mek1 /2", "mek1 /2 but leads", "/2 but leads to", "but leads to the", "leads to the phosphorylation", "to the phosphorylation and", "the phosphorylation and subsequent", "phosphorylation and subsequent acetylation", "and subsequent acetylation of", "subsequent acetylation of rela", "of rela p65", "rela p65 .", "p65 . rela phosphorylated", ". rela phosphorylated on", "rela phosphorylated on s276", "phosphorylated on s276 not", "on s276 not only", "s276 not only positively", "not only positively regulates", "only positively regulates the", "positively regulates the activity", "regulates the activity of", "the activity of p65", "activity of p65 through", "of p65 through acetylation", "p65 through acetylation of", "through acetylation of p65", "of p65 but", "p65 but also", "but also represses relb", "also represses relb activity", "represses relb activity by", "relb activity by sequestering", "activity by sequestering active", "by sequestering active relb", "sequestering active relb into", "active relb into inactive", "relb into inactive p65", "into inactive p65 relb", "inactive p65 relb dimers", "p65 relb dimers that", "relb dimers that do", "dimers that do not", "that do not bind", "do not bind dna", "bind dna gringhuis", "dna gringhuis et", "al. 2007 svajger", "2007 svajger et", "al. 2010 jacque", "2010 jacque et", "jacque et al. 2005", "et al. 2005 .", "al. 2005 . raf1", "2005 . raf1 dependent", ". raf1 dependent signaling", "raf1 dependent signaling pathway", "dependent signaling pathway is", "signaling pathway is crucial", "pathway is crucial in", "is crucial in dectin", "crucial in dectin 1", "in dectin 1 mediated", "dectin 1 mediated immunity", "1 mediated immunity as", "mediated immunity as it", "immunity as it modulates", "as it modulates both", "it modulates both the", "modulates both the canonical", "the canonical promoting", "canonical promoting p65", "promoting p65 phosphorylation and", "p65 phosphorylation and acetylation", "and acetylation and", "acetylation and non", "non canonical forming", "canonical forming inactive", "forming inactive p65 relb", "relb dimers nk", "dimers nk kb", "cd209 also called as", "also called as dc sign", "as dc sign dc", "dc sign dc specific", "sign dc specific intracellular", "dc specific intracellular adhesion molecule", "specific intracellular adhesion molecule 3", "intracellular adhesion molecule 3 grabbing", "adhesion molecule 3 grabbing non", "molecule 3 grabbing non integrin", "non integrin is", "integrin is a", "is a type ii transmembrane", "a type ii transmembrane c", "type ii transmembrane c type", "ii transmembrane c type lectin", "transmembrane c type lectin receptor", "c type lectin receptor preferentially", "type lectin receptor preferentially expressed", "lectin receptor preferentially expressed on", "receptor preferentially expressed on dendritic", "preferentially expressed on dendritic cells", "on dendritic cells dcs", "dendritic cells dcs .", "cells dcs . cd209", "dcs . cd209 functions as", ". cd209 functions as a", "cd209 functions as a pattern", "functions as a pattern recognition", "as a pattern recognition receptor", "pattern recognition receptor prr", "receptor prr that", "prr that recognises several", "that recognises several microorganisms and", "recognises several microorganisms and pathogens", "microorganisms and pathogens contributing", "and pathogens contributing to", "pathogens contributing to generation", "contributing to generation of pathogen", "to generation of pathogen tailored", "generation of pathogen tailored immune", "of pathogen tailored immune responses", "tailored immune responses gringhuis", "immune responses gringhuis &", "responses gringhuis & geijtenbeek", "& geijtenbeek 2010 den", "geijtenbeek 2010 den dunnen", "2010 den dunnen et", "den dunnen et al. 2009", "et al. 2009 svajger", "al. 2009 svajger et", "2009 svajger et al.", "svajger et al. 2010 .", "et al. 2010 . cd209", "al. 2010 . cd209 interacts", "2010 . cd209 interacts with", ". cd209 interacts with different", "cd209 interacts with different mannose", "interacts with different mannose expressing", "with different mannose expressing pathogens", "different mannose expressing pathogens such", "mannose expressing pathogens such as", "expressing pathogens such as mycobacterium", "pathogens such as mycobacterium tuberculosis", "such as mycobacterium tuberculosis and", "as mycobacterium tuberculosis and hiv", "mycobacterium tuberculosis and hiv 1", "and hiv 1 gringhuis", "hiv 1 gringhuis et", "1 gringhuis et al.", "et al. 2007 geijtenbeek", "al. 2007 geijtenbeek et", "2007 geijtenbeek et al.", "geijtenbeek et al. 2000a .", "et al. 2000a . it", "al. 2000a . it also", "2000a . it also acts", ". it also acts as", "it also acts as an", "also acts as an adhesion", "acts as an adhesion receptor", "as an adhesion receptor that", "an adhesion receptor that interacts", "adhesion receptor that interacts with", "receptor that interacts with icam2", "interacts with icam2 intracellular", "with icam2 intracellular adhesion", "icam2 intracellular adhesion molecule", "adhesion molecule 2 on", "molecule 2 on endothelial", "2 on endothelial cells", "on endothelial cells and icam3", "endothelial cells and icam3 on", "cells and icam3 on t", "and icam3 on t cells", "on t cells geijtenbeek", "t cells geijtenbeek et", "cells geijtenbeek et al.", "geijtenbeek et al. 2000b c", "et al. 2000b c .", "al. 2000b c . cd209", "2000b c . cd209 functions", "c . cd209 functions not", ". cd209 functions not only", "cd209 functions not only as", "functions not only as an", "not only as an independent", "only as an independent prr", "an independent prr but", "independent prr but is", "prr but is also", "but is also implicated in", "is also implicated in the", "also implicated in the modulation", "implicated in the modulation of", "in the modulation of toll", "the modulation of toll like", "modulation of toll like receptor", "toll like receptor tlr", "receptor tlr signaling", "tlr signaling at the", "signaling at the level of", "at the level of the", "the level of the transcription", "level of the transcription factor", "of the transcription factor nf", "the transcription factor nf kb", "factor nf kb gringhuis", "nf kb gringhuis et", "kb gringhuis et al.", "gringhuis et al. 2009 .", "et al. 2009 . clec7a", "2009 . clec7a dectin", ". clec7a dectin 1", "dectin 1 and cd209", "and cd209 dc sign", "dc sign signalling modulates", "sign signalling modulates toll", "signalling modulates toll like receptor", "receptor tlr signalling", "tlr signalling through the", "signalling through the kinase raf1", "through the kinase raf1 that", "the kinase raf1 that is", "kinase raf1 that is independent", "raf1 that is independent of", "that is independent of the", "is independent of the syk", "independent of the syk pathway", "of the syk pathway but", "the syk pathway but integrated", "syk pathway but integrated with", "pathway but integrated with it", "but integrated with it at", "integrated with it at the", "with it at the level", "it at the level of", "at the level of nf", "the level of nf kb", "level of nf kb activation.", "of nf kb activation. the", "nf kb activation. the activation", "kb activation. the activation of", "activation. the activation of raf1", "the activation of raf1 by", "activation of raf1 by clec7a", "of raf1 by clec7a or", "raf1 by clec7a or cd209", "by clec7a or cd209 does", "clec7a or cd209 does not", "or cd209 does not lead", "cd209 does not lead to", "does not lead to activation", "not lead to activation of", "lead to activation of extracellular", "to activation of extracellular signal", "activation of extracellular signal regulated", "of extracellular signal regulated kinase", "extracellular signal regulated kinase 1", "regulated kinase 1 erk1", "kinase 1 erk1 /2", "1 erk1 /2 or", "erk1 /2 or mitogen activated", "/2 or mitogen activated protein", "or mitogen activated protein kinase", "mitogen activated protein kinase kinase", "activated protein kinase kinase 1", "kinase kinase 1 mek1", "kinase 1 mek1 /2", "1 mek1 /2 but", "mek1 /2 but leads to", "/2 but leads to the", "but leads to the phosphorylation", "leads to the phosphorylation and", "to the phosphorylation and subsequent", "the phosphorylation and subsequent acetylation", "phosphorylation and subsequent acetylation of", "and subsequent acetylation of rela", "acetylation of rela p65", "of rela p65 .", "rela p65 . rela", "p65 . rela phosphorylated on", ". rela phosphorylated on s276", "rela phosphorylated on s276 not", "phosphorylated on s276 not only", "on s276 not only positively", "s276 not only positively regulates", "not only positively regulates the", "only positively regulates the activity", "positively regulates the activity of", "regulates the activity of p65", "the activity of p65 through", "activity of p65 through acetylation", "of p65 through acetylation of", "p65 through acetylation of p65", "acetylation of p65 but", "of p65 but also", "p65 but also represses", "but also represses relb activity", "also represses relb activity by", "represses relb activity by sequestering", "relb activity by sequestering active", "activity by sequestering active relb", "by sequestering active relb into", "sequestering active relb into inactive", "active relb into inactive p65", "relb into inactive p65 relb", "into inactive p65 relb dimers", "inactive p65 relb dimers that", "p65 relb dimers that do", "relb dimers that do not", "dimers that do not bind", "that do not bind dna", "not bind dna gringhuis", "bind dna gringhuis et", "dna gringhuis et al.", "et al. 2007 svajger", "al. 2007 svajger et", "2007 svajger et al.", "et al. 2010 jacque", "al. 2010 jacque et", "2010 jacque et al.", "jacque et al. 2005 .", "et al. 2005 . raf1", "al. 2005 . raf1 dependent", "2005 . raf1 dependent signaling", ". raf1 dependent signaling pathway", "raf1 dependent signaling pathway is", "dependent signaling pathway is crucial", "signaling pathway is crucial in", "pathway is crucial in dectin", "is crucial in dectin 1", "crucial in dectin 1 mediated", "in dectin 1 mediated immunity", "dectin 1 mediated immunity as", "1 mediated immunity as it", "mediated immunity as it modulates", "immunity as it modulates both", "as it modulates both the", "it modulates both the canonical", "both the canonical promoting", "the canonical promoting p65", "canonical promoting p65 phosphorylation", "promoting p65 phosphorylation and acetylation", "phosphorylation and acetylation and", "and acetylation and non", "acetylation and non canonical", "and non canonical forming", "non canonical forming inactive", "canonical forming inactive p65", "forming inactive p65 relb dimers", "p65 relb dimers nk", "relb dimers nk kb", "dimers nk kb activation." ] }, { "record_id": "GLY_000594_1_1029", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5624958", "r hsa", "hsa 5624958", "r hsa 5624958" ] }, { "record_id": "GLY_000594_1_1029", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "arl13b mediated", "mediated ciliary", "ciliary trafficking", "trafficking of", "of inpp5e", "arl13b mediated ciliary", "mediated ciliary trafficking", "ciliary trafficking of", "trafficking of inpp5e", "arl13b mediated ciliary trafficking", "mediated ciliary trafficking of", "ciliary trafficking of inpp5e", "arl13b mediated ciliary trafficking of", "mediated ciliary trafficking of inpp5e", "arl13b is", "is a", "a ciliary", "ciliary localized", "localized small", "small gtpase", "gtpase with", "with an", "an atypical", "atypical c", "c terminus", "terminus containing", "containing a", "a coiled", "coiled coil", "coil domain", "domain and", "and a", "a proline", "proline rich", "rich domain", "hori et", "et al", "2008 .", ". mutations", "mutations in", "in arl13b", "arl13b are", "are associated", "associated with", "with the", "the development", "development of", "of the", "the ciliopathy", "ciliopathy joubert's", "joubert's syndrome", "cantagrel et", "parisi et", "2009 .", ". studies", "studies in", "in c.", "c. elegans", "elegans and", "and vertebrates", "vertebrates suggest", "suggest that", "that arl13b", "arl13b may", "may play", "play a", "a role", "role in", "in stabilizing", "stabilizing the", "the interaction", "interaction between", "between the", "the ift", "ift a", "a and", "and b", "b complexes", "complexes and", "and the", "the kinesin", "kinesin 2", "2 motors", "motors during", "during anterograde", "anterograde traffic", "traffic in", "in the", "the cilium", "cevik et", "li et", "reviewed in", "in li", "zhang et", "2013 .", ". recent", "recent work", "work has", "has shown", "shown an", "an additional", "additional role", "role for", "for arl13b", "arl13b in", "in trafficking", "trafficking the", "the inositol", "inositol polyphosphate", "polyphosphate 5", "5 phosphatase", "phosphatase e", "to the", "cilium through", "through a", "a network", "network that", "that also", "also involves", "involves the", "the phosphodiesterase", "phosphodiesterase pde6d", "pde6d and", "the centriolar", "centriolar protein", "protein cep164", "humbert et", "thomas et", "in zhang", "in inpp5e", "inpp5e are", "are also", "also associated", "of joubert", "joubert syndrome", "syndrome and", "and other", "other ciliopathies", "bielas et", "jacoby et", "in conduit", "conduit et", "2012 .", "arl13b is a", "is a ciliary", "a ciliary localized", "ciliary localized small", "localized small gtpase", "small gtpase with", "gtpase with an", "with an atypical", "an atypical c", "atypical c terminus", "c terminus containing", "terminus containing a", "containing a coiled", "a coiled coil", "coiled coil domain", "coil domain and", "domain and a", "and a proline", "a proline rich", "proline rich domain", "domain prd", "hori et al", "al 2008", "2008 . mutations", ". mutations in", "mutations in arl13b", "in arl13b are", "arl13b are associated", "are associated with", "associated with the", "with the development", "the development of", "development of the", "of the ciliopathy", "the ciliopathy joubert's", "ciliopathy joubert's syndrome", "syndrome cantagrel", "cantagrel et al", "2008 parisi", "parisi et al", "al 2009", "2009 . studies", ". studies in", "studies in c.", "in c. elegans", "c. elegans and", "elegans and vertebrates", "and vertebrates suggest", "vertebrates suggest that", "suggest that arl13b", "that arl13b may", "arl13b may play", "may play a", "play a role", "a role in", "role in stabilizing", "in stabilizing the", "stabilizing the interaction", "the interaction between", "interaction between the", "between the ift", "the ift a", "ift a and", "a and b", "and b complexes", "b complexes and", "complexes and the", "and the kinesin", "the kinesin 2", "kinesin 2 motors", "2 motors during", "motors during anterograde", "during anterograde traffic", "anterograde traffic in", "traffic in the", "in the cilium", "cilium cevik", "cevik et al", "al 2010", "2010 li", "li et al", "2010 cevik", "al 2013", "2013 reviewed", "reviewed in li", "in li et", "al 2012", "2012 zhang", "zhang et al", "2013 . recent", ". recent work", "recent work has", "work has shown", "has shown an", "shown an additional", "an additional role", "additional role for", "role for arl13b", "for arl13b in", "arl13b in trafficking", "in trafficking the", "trafficking the inositol", "the inositol polyphosphate", "inositol polyphosphate 5", "polyphosphate 5 phosphatase", "5 phosphatase e", "e inpp5e", "inpp5e to", "to the cilium", "the cilium through", "cilium through a", "through a network", "a network that", "network that also", "that also involves", "also involves the", "involves the phosphodiesterase", "the phosphodiesterase pde6d", "phosphodiesterase pde6d and", "pde6d and the", "and the centriolar", "the centriolar protein", "centriolar protein cep164", "cep164 humbert", "humbert et al", "2012 thomas", "thomas et al", "al 2014", "2014 reviewed", "reviewed in zhang", "in zhang et", "2013 . mutations", "mutations in inpp5e", "in inpp5e are", "inpp5e are also", "are also associated", "also associated with", "development of joubert", "of joubert syndrome", "joubert syndrome and", "syndrome and other", "and other ciliopathies", "ciliopathies bielas", "bielas et al", "2009 jacoby", "jacoby et al", "2009 reviewed", "reviewed in conduit", "in conduit et", "conduit et al", "arl13b is a ciliary", "is a ciliary localized", "a ciliary localized small", "ciliary localized small gtpase", "localized small gtpase with", "small gtpase with an", "gtpase with an atypical", "with an atypical c", "an atypical c terminus", "atypical c terminus containing", "c terminus containing a", "terminus containing a coiled", "containing a coiled coil", "a coiled coil domain", "coiled coil domain and", "coil domain and a", "domain and a proline", "and a proline rich", "a proline rich domain", "rich domain prd", "prd hori", "et al 2008", "al 2008 .", "2008 . mutations in", ". mutations in arl13b", "mutations in arl13b are", "in arl13b are associated", "arl13b are associated with", "are associated with the", "associated with the development", "with the development of", "the development of the", "development of the ciliopathy", "of the ciliopathy joubert's", "the ciliopathy joubert's syndrome", "joubert's syndrome cantagrel", "syndrome cantagrel et", "2008 parisi et", "et al 2009", "al 2009 .", "2009 . studies in", ". studies in c.", "studies in c. elegans", "in c. elegans and", "c. elegans and vertebrates", "elegans and vertebrates suggest", "and vertebrates suggest that", "vertebrates suggest that arl13b", "suggest that arl13b may", "that arl13b may play", "arl13b may play a", "may play a role", "play a role in", "a role in stabilizing", "role in stabilizing the", "in stabilizing the interaction", "stabilizing the interaction between", "the interaction between the", "interaction between the ift", "between the ift a", "the ift a and", "ift a and b", "a and b complexes", "and b complexes and", "b complexes and the", "complexes and the kinesin", "and the kinesin 2", "the kinesin 2 motors", "kinesin 2 motors during", "2 motors during anterograde", "motors during anterograde traffic", "during anterograde traffic in", "anterograde traffic in the", "traffic in the cilium", "the cilium cevik", "cilium cevik et", "et al 2010", "2010 li et", "2010 cevik et", "et al 2013", "2013 reviewed in", "reviewed in li et", "in li et al", "et al 2012", "2012 zhang et", "al 2013 .", "2013 . recent work", ". recent work has", "recent work has shown", "work has shown an", "has shown an additional", "shown an additional role", "an additional role for", "additional role for arl13b", "role for arl13b in", "for arl13b in trafficking", "arl13b in trafficking the", "in trafficking the inositol", "trafficking the inositol polyphosphate", "the inositol polyphosphate 5", "inositol polyphosphate 5 phosphatase", "polyphosphate 5 phosphatase e", "phosphatase e inpp5e", "inpp5e to the", "to the cilium through", "the cilium through a", "cilium through a network", "through a network that", "a network that also", "network that also involves", "that also involves the", "also involves the phosphodiesterase", "involves the phosphodiesterase pde6d", "the phosphodiesterase pde6d and", "phosphodiesterase pde6d and the", "pde6d and the centriolar", "and the centriolar protein", "the centriolar protein cep164", "protein cep164 humbert", "cep164 humbert et", "2012 thomas et", "et al 2014", "2014 reviewed in", "reviewed in zhang et", "in zhang et al", "2013 . mutations in", ". mutations in inpp5e", "mutations in inpp5e are", "in inpp5e are also", "inpp5e are also associated", "are also associated with", "also associated with the", "the development of joubert", "development of joubert syndrome", "of joubert syndrome and", "joubert syndrome and other", "syndrome and other ciliopathies", "other ciliopathies bielas", "ciliopathies bielas et", "2009 jacoby et", "2009 reviewed in", "reviewed in conduit et", "in conduit et al", "al 2012 .", "arl13b is a ciliary localized", "is a ciliary localized small", "a ciliary localized small gtpase", "ciliary localized small gtpase with", "localized small gtpase with an", "small gtpase with an atypical", "gtpase with an atypical c", "with an atypical c terminus", "an atypical c terminus containing", "atypical c terminus containing a", "c terminus containing a coiled", "terminus containing a coiled coil", "containing a coiled coil domain", "a coiled coil domain and", "coiled coil domain and a", "coil domain and a proline", "domain and a proline rich", "and a proline rich domain", "proline rich domain prd", "prd hori et", "hori et al 2008", "et al 2008 .", "al 2008 . mutations", "2008 . mutations in arl13b", ". mutations in arl13b are", "mutations in arl13b are associated", "in arl13b are associated with", "arl13b are associated with the", "are associated with the development", "associated with the development of", "with the development of the", "the development of the ciliopathy", "development of the ciliopathy joubert's", "of the ciliopathy joubert's syndrome", "ciliopathy joubert's syndrome cantagrel", "joubert's syndrome cantagrel et", "syndrome cantagrel et al", "cantagrel et al 2008", "al 2008 parisi", "2008 parisi et al", "parisi et al 2009", "et al 2009 .", "al 2009 . studies", "2009 . studies in c.", ". studies in c. elegans", "studies in c. elegans and", "in c. elegans and vertebrates", "c. elegans and vertebrates suggest", "elegans and vertebrates suggest that", "and vertebrates suggest that arl13b", "vertebrates suggest that arl13b may", "suggest that arl13b may play", "that arl13b may play a", "arl13b may play a role", "may play a role in", "play a role in stabilizing", "a role in stabilizing the", "role in stabilizing the interaction", "in stabilizing the interaction between", "stabilizing the interaction between the", "the interaction between the ift", "interaction between the ift a", "between the ift a and", "the ift a and b", "ift a and b complexes", "a and b complexes and", "and b complexes and the", "b complexes and the kinesin", "complexes and the kinesin 2", "and the kinesin 2 motors", "the kinesin 2 motors during", "kinesin 2 motors during anterograde", "2 motors during anterograde traffic", "motors during anterograde traffic in", "during anterograde traffic in the", "anterograde traffic in the cilium", "in the cilium cevik", "the cilium cevik et", "cilium cevik et al", "cevik et al 2010", "al 2010 li", "2010 li et al", "li et al 2010", "al 2010 cevik", "2010 cevik et al", "cevik et al 2013", "al 2013 reviewed", "2013 reviewed in li", "reviewed in li et al", "li et al 2012", "al 2012 zhang", "2012 zhang et al", "zhang et al 2013", "et al 2013 .", "al 2013 . recent", "2013 . recent work has", ". recent work has shown", "recent work has shown an", "work has shown an additional", "has shown an additional role", "shown an additional role for", "an additional role for arl13b", "additional role for arl13b in", "role for arl13b in trafficking", "for arl13b in trafficking the", "arl13b in trafficking the inositol", "in trafficking the inositol polyphosphate", "trafficking the inositol polyphosphate 5", "the inositol polyphosphate 5 phosphatase", "inositol polyphosphate 5 phosphatase e", "5 phosphatase e inpp5e", "e inpp5e to", "inpp5e to the cilium", "to the cilium through a", "the cilium through a network", "cilium through a network that", "through a network that also", "a network that also involves", "network that also involves the", "that also involves the phosphodiesterase", "also involves the phosphodiesterase pde6d", "involves the phosphodiesterase pde6d and", "the phosphodiesterase pde6d and the", "phosphodiesterase pde6d and the centriolar", "pde6d and the centriolar protein", "and the centriolar protein cep164", "centriolar protein cep164 humbert", "protein cep164 humbert et", "cep164 humbert et al", "humbert et al 2012", "al 2012 thomas", "2012 thomas et al", "thomas et al 2014", "al 2014 reviewed", "2014 reviewed in zhang", "reviewed in zhang et al", "al 2013 . mutations", "2013 . mutations in inpp5e", ". mutations in inpp5e are", "mutations in inpp5e are also", "in inpp5e are also associated", "inpp5e are also associated with", "are also associated with the", "also associated with the development", "with the development of joubert", "the development of joubert syndrome", "development of joubert syndrome and", "of joubert 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production", "tnfr1 mediated ceramide", "mediated ceramide production", "tnfr1 mediated ceramide production", "tnf alpha", "alpha activates", "activates sphingomyelinase", "proteins to", "to catalyze", "catalyze hydrolysis", "hydrolysis of", "of sphingomyeline", "sphingomyeline into", "into ceramide.", "ceramide. two", "two types", "types of", "of smase", "smase can", "can be", "be distinguished", "distinguished downstream", "downstream of", "of tnfr1", "tnfr1 signaling", "acid and", "and neutral", "neutral smases", "adam klages", "klages s", "s et", "et al.", "al. 1996", "1998 .", ". neutral", "neutral smase", "such as", "as smpd2", "smpd2 3", "has a", "a ph", "ph optimum", "optimum of", "of 7.4", "requires mg2+", "mg2+ ions", "ions and", "and is", "is found", "found at", "at the", "the plasma", "plasma membrane", "rao bg", "bg and", "and spence", "spence mw", "mw 1976", "1976 .", ". acid", "acid smase", "smase is", "is active", "active at", "at ph", "ph 4", "4 5", "is zn2+", "zn2+ dependent", "dependent and", "is mainly", "mainly localized", "localized in", "in the", "the lysosomes.", "lysosomes. the", "the death", "death domain", "domain of", "tnfr1 that", "that is", "is responsible", "responsible for", "for the", "the initiation", "initiation of", "of the", "the apoptotic", "apoptotic pathway", "pathway also", "also mediates", "mediates activation", "activation of", "of an", "an acid", "acid smase.", "smase. the", "the two", "two proapoptotic", "proapoptotic adaptor", "adaptor proteins", "proteins tradd", "tradd and", "and fadd", "fadd are", "are also", "also involved", "involved in", "the activation", "of acid", "smase signaling", "signaling events", "schwandner r", "r et", "al. 1998", ". tnf", "alpha can", "can also", "also activate", "activate the", "the pro", "pro apoptotic", "acidic smase", "smase via", "via caspase", "caspase 8", "8 mediated", "mediated activation", "of caspase", "caspase 7", "7 which", "which in", "in turn", "turn proteolytically", 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              ceramide", "surface.

              ceramide metabolism", "metabolism generates", "generates a", "a cascade", "cascade of", "of bioactive", "bioactive lipids", "all of", "of which", "which carry", "carry a", "a specific", "specific signaling", "signaling capacity.", "capacity. ceramide", "ceramide can", "be converted", "converted by", "by ceramidase", "ceramidase into", "into sphingosine", "turn is", "is phosphorylated", "phosphorylated by", "by sphingosine", "sphingosine kinase", "kinase into", "sphingosine 1", "1 phosphate", "s1p .", ". these", "these lipids", "lipids exert", "exert opposite", "opposite biological", "biological effects:", "effects: ceramide", "ceramide and", "and sphingosine", "sphingosine are", "are able", "able to", "to induce", "induce anti", "anti proliferative", "proliferative and", "and pro", "apoptotic responses", "whereas s1p", "s1p is", "is a", "a cytoprotective", "cytoprotective molecule", "molecule that", "that promotes", "promotes cell", "cell growth", "growth and", "and counteracts", "counteracts apoptotic", "apoptotic stimuli", "cuvillier o", "o et", "et al.1996", "tnf alpha activates", "alpha activates sphingomyelinase", "sphingomyelinase smase", "smase proteins", "proteins to catalyze", "to catalyze hydrolysis", "catalyze hydrolysis of", "hydrolysis of sphingomyeline", "of sphingomyeline into", "sphingomyeline into ceramide.", "into ceramide. two", "ceramide. two types", "two types of", "types of smase", "of smase can", "smase can be", "can be distinguished", "be distinguished downstream", "distinguished downstream of", "downstream of tnfr1", "of tnfr1 signaling", "signaling acid", "acid and neutral", "and neutral smases", "smases adam", "adam klages s", "klages s et", "s et al.", "et al. 1996", "1996 1998", "1998 . neutral", ". neutral smase", "smase such", "such as smpd2", "as smpd2 3", "3 has", "has a ph", "a ph optimum", "ph optimum of", "optimum of 7.4", "7.4 requires", "requires mg2+ ions", "mg2+ ions and", "ions and is", "and is found", "is found at", "found at the", "at the plasma", "the plasma membrane", "membrane rao", "rao bg and", "bg and spence", "and spence mw", "spence mw 1976", "mw 1976 .", "1976 . acid", ". acid smase", "acid smase is", "smase is active", "is active at", "active at ph", "at ph 4", "ph 4 5", "5 is", "is zn2+ dependent", "zn2+ dependent and", "dependent and is", "and is mainly", "is mainly localized", "mainly localized in", "localized in the", "in the lysosomes.", "the lysosomes. the", "lysosomes. the death", "the death domain", "death domain of", "domain of tnfr1", "of tnfr1 that", "tnfr1 that is", "that is responsible", "is responsible for", "responsible for the", "for the initiation", "the initiation of", "initiation of the", "of the apoptotic", "the apoptotic pathway", "apoptotic pathway also", "pathway also mediates", "also mediates activation", "mediates activation of", "activation of an", "of an acid", "an acid smase.", "acid smase. the", "smase. the two", "the two proapoptotic", "two proapoptotic adaptor", "proapoptotic adaptor proteins", "adaptor proteins tradd", "proteins tradd and", "tradd and fadd", "and fadd are", "fadd are also", "are also involved", "also involved in", "involved in the", "in the activation", "the activation of", "activation of acid", "of acid smase", "acid smase signaling", "smase signaling events", "events schwandner", "schwandner r et", "r et al.", "et al. 1998", "al. 1998 .", "1998 . tnf", ". tnf alpha", "tnf alpha can", "alpha can also", "can also activate", "also activate the", "activate the pro", "the pro apoptotic", "apoptotic acidic", "acidic smase via", "smase via caspase", "via caspase 8", "caspase 8 mediated", "8 mediated activation", "mediated activation of", "activation of caspase", "of caspase 7", "caspase 7 which", "7 which in", "which in turn", "in turn proteolytically", "turn proteolytically cleaves", "proteolytically cleaves and", "cleaves and activates", "and activates the", "activates the 72kda", "the 72kda pro", "72kda pro acid", "pro acid smase", "acid smase form", "form edelmann", "edelmann b et", "b et al.", "et al. 2011", "al. 2011 .", "2011 . neutral", "neutral smase smpd", "smpd binds", "binds to adaptor", "to adaptor protein", "adaptor protein nsmaf", "nsmaf fan", "which bridges it", "bridges it to", "it to nsmase", "to nsmase activating", "nsmase activating domain", "domain nsd", "nsd of", "tnfr1 adam", "adam d et", "d et al.", "1996 adam", "1996 s\u00e9gui", "s\u00e9gui b et", "et al. 2001", "al. 2001 .", "2001 . activation", ". activation of", "activation of smpd2", "of smpd2 3", "smpd2 3 leads", "3 leads to", "leads to an", "to an accumulation", "an accumulation of", "accumulation of ceramide", "of ceramide at", "ceramide at the", "at the cell", "the cell surface.

              ceramide", "cell surface.

              ceramide metabolism", "surface.

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are", "sphingosine are able", "are able to", "able to induce", "to induce anti", "induce anti proliferative", "anti proliferative and", "proliferative and pro", "and pro apoptotic", "pro apoptotic responses", "responses whereas", "whereas s1p is", "s1p is a", "is a cytoprotective", "a cytoprotective molecule", "cytoprotective molecule that", "molecule that promotes", "that promotes cell", "promotes cell growth", "cell growth and", "growth and counteracts", "and counteracts apoptotic", "counteracts apoptotic stimuli", "stimuli cuvillier", "cuvillier o et", "o et al.1996", "tnf alpha activates sphingomyelinase", "activates sphingomyelinase smase", "smase proteins to", "proteins to catalyze hydrolysis", "to catalyze hydrolysis of", "catalyze hydrolysis of sphingomyeline", "hydrolysis of sphingomyeline into", "of sphingomyeline into ceramide.", "sphingomyeline into ceramide. two", "into ceramide. two types", "ceramide. two types of", "two types of smase", "types of smase can", "of smase can be", "smase can be distinguished", "can be distinguished downstream", "be distinguished downstream of", "distinguished downstream of tnfr1", "downstream of tnfr1 signaling", "tnfr1 signaling acid", "signaling acid and", "acid and neutral smases", "neutral smases adam", "smases adam klages", "adam klages s et", "klages s et al.", "s et al. 1996", "al. 1996 1998", "1996 1998 .", "1998 . neutral smase", "neutral smase such", "smase such as", "such as smpd2 3", "smpd2 3 has", "3 has a", "has a ph optimum", "a ph optimum of", "ph optimum of 7.4", "of 7.4 requires", "7.4 requires mg2+", "requires mg2+ ions and", "mg2+ ions and is", "ions and is found", "and is found at", "is found at the", "found at the plasma", "at the plasma membrane", "plasma membrane rao", "membrane rao bg", "rao bg and spence", "bg and spence mw", "and spence mw 1976", "spence mw 1976 .", "mw 1976 . acid", "1976 . acid smase", ". acid smase is", "acid smase is active", "smase is active at", "is active at ph", "active at ph 4", "at ph 4 5", "4 5 is", "5 is zn2+", "is zn2+ dependent and", "zn2+ dependent and is", "dependent and is mainly", "and is mainly localized", "is mainly localized in", "mainly localized in the", "localized in the lysosomes.", "in the lysosomes. the", "the lysosomes. the death", "lysosomes. the death domain", "the death domain of", "death domain of tnfr1", "domain of tnfr1 that", "of tnfr1 that is", "tnfr1 that is responsible", "that is responsible for", "is responsible for the", "responsible for the initiation", "for the initiation of", "the initiation of the", "initiation of the apoptotic", "of the apoptotic pathway", "the apoptotic pathway also", "apoptotic pathway also mediates", "pathway also mediates activation", "also mediates activation of", "mediates activation of an", "activation of an acid", "of an acid smase.", "an acid smase. the", "acid smase. the two", "smase. the two proapoptotic", "the two proapoptotic adaptor", "two proapoptotic adaptor proteins", "proapoptotic adaptor proteins tradd", "adaptor proteins tradd and", "proteins tradd and fadd", "tradd and fadd are", "and fadd are also", "fadd are also involved", "are also involved in", "also involved in the", "involved in the activation", "in the activation of", "the activation of acid", "activation of acid smase", "of acid smase signaling", "acid smase signaling events", "signaling events schwandner", "events schwandner r", "schwandner r et al.", "r et al. 1998", "et al. 1998 .", "al. 1998 . tnf", "1998 . tnf alpha", ". tnf alpha can", "tnf alpha can also", "alpha can also activate", "can also activate the", "also activate the pro", "activate the pro apoptotic", "pro apoptotic acidic", "apoptotic acidic smase", "acidic smase via caspase", "smase via caspase 8", "via caspase 8 mediated", "caspase 8 mediated activation", "8 mediated activation of", "mediated activation of caspase", "activation of caspase 7", "of caspase 7 which", "caspase 7 which in", "7 which in turn", "which in turn proteolytically", "in turn proteolytically cleaves", "turn proteolytically cleaves and", "proteolytically cleaves and activates", "cleaves and activates the", "and activates the 72kda", "activates the 72kda pro", "the 72kda pro acid", "72kda pro acid smase", "pro acid smase form", "smase form edelmann", "form edelmann b", "edelmann b et al.", "b et al. 2011", "et al. 2011 .", "al. 2011 . neutral", "2011 . neutral smase", ". neutral smase smpd", "smase smpd binds", "smpd binds to", "binds to adaptor protein", "to adaptor protein nsmaf", "protein nsmaf fan", "fan which", "which bridges it to", "bridges it to nsmase", "it to nsmase activating", "to nsmase activating domain", "activating domain nsd", "nsd of tnfr1", "of tnfr1 adam", "tnfr1 adam d", "adam d et al.", "d et al. 1996", "al. 1996 adam", "1996 adam klages", "al. 1996 s\u00e9gui", "1996 s\u00e9gui b", "s\u00e9gui b et al.", "b et al. 2001", "et al. 2001 .", "al. 2001 . activation", "2001 . activation of", ". activation of smpd2", "activation of smpd2 3", "of smpd2 3 leads", "smpd2 3 leads to", "3 leads to an", "leads to an accumulation", "to an accumulation of", "an accumulation of ceramide", "accumulation of ceramide at", "of ceramide at the", "ceramide at the cell", "at the cell surface.

              ceramide", "the cell surface.

              ceramide metabolism", "cell surface.

              ceramide metabolism generates", "surface.

              ceramide metabolism generates a", "metabolism generates a cascade", "generates a cascade of", "a cascade of bioactive", "cascade of bioactive lipids", "bioactive lipids all", "lipids all of", "all of which carry", "of which carry a", "which carry a specific", "carry a specific signaling", "a specific signaling capacity.", "specific signaling capacity. ceramide", "signaling capacity. ceramide can", "capacity. ceramide can be", "ceramide can be converted", "can be converted by", "be converted by ceramidase", "converted by ceramidase into", "by ceramidase into sphingosine", "into sphingosine which", "sphingosine which in", "which in turn is", "in turn is phosphorylated", "turn is phosphorylated by", "is phosphorylated by sphingosine", "phosphorylated by sphingosine kinase", "by sphingosine kinase into", "sphingosine kinase into sphingosine", "kinase into sphingosine 1", "into sphingosine 1 phosphate", "1 phosphate s1p", "phosphate s1p .", "s1p . these lipids", ". these lipids exert", "these lipids exert opposite", "lipids exert opposite biological", "exert opposite biological effects:", "opposite biological effects: ceramide", "biological effects: ceramide and", "effects: ceramide and sphingosine", "ceramide and sphingosine are", "and sphingosine are able", "sphingosine are able to", "are able to induce", "able to induce anti", "to induce anti proliferative", "induce anti proliferative and", "anti proliferative and pro", "proliferative and pro apoptotic", "and pro apoptotic responses", "apoptotic responses whereas", "responses whereas s1p", "whereas s1p is a", "s1p is a cytoprotective", "is a cytoprotective molecule", "a cytoprotective molecule that", "cytoprotective molecule that promotes", "molecule that promotes cell", "that promotes cell growth", "promotes cell growth and", "cell growth and counteracts", "growth and counteracts apoptotic", "and counteracts apoptotic stimuli", "apoptotic stimuli cuvillier", "stimuli cuvillier o", "cuvillier o et al.1996", "alpha activates sphingomyelinase smase", "sphingomyelinase smase proteins", "smase proteins to catalyze", "proteins to catalyze hydrolysis of", "to catalyze hydrolysis of sphingomyeline", "catalyze hydrolysis of sphingomyeline into", "hydrolysis of sphingomyeline into ceramide.", "of sphingomyeline into ceramide. two", "sphingomyeline into ceramide. two types", "into ceramide. two types of", "ceramide. two types of smase", "two types of smase can", "types of smase can be", "of smase can be distinguished", "smase can be distinguished downstream", "can be distinguished downstream of", "be distinguished downstream of tnfr1", "distinguished downstream of tnfr1 signaling", "of tnfr1 signaling acid", "tnfr1 signaling acid and", "signaling acid and neutral", "and neutral smases adam", "neutral smases adam klages", "smases adam klages s", "adam klages s et al.", "klages s et al. 1996", "et al. 1996 1998", "al. 1996 1998 .", "1996 1998 . neutral", ". neutral smase such", "neutral smase such as", "smase such as smpd2", "as smpd2 3 has", "smpd2 3 has a", "3 has a ph", "has a ph optimum of", "a ph optimum of 7.4", "optimum of 7.4 requires", "of 7.4 requires mg2+", "7.4 requires mg2+ ions", "requires mg2+ ions and is", "mg2+ ions and is found", "ions and is found at", "and is found at the", "is found at the plasma", "found at the plasma membrane", "the plasma membrane rao", "plasma membrane rao bg", "membrane rao bg and", "rao bg and spence mw", "bg and spence mw 1976", "and spence mw 1976 .", "spence mw 1976 . acid", "mw 1976 . acid smase", "1976 . acid smase is", ". acid smase is active", "acid smase is active at", "smase is active at ph", "is active at ph 4", "active at ph 4 5", "ph 4 5 is", "4 5 is zn2+", "5 is zn2+ dependent", "is zn2+ dependent and is", "zn2+ dependent and is mainly", "dependent and is mainly localized", "and is mainly localized in", "is mainly localized in the", "mainly localized in the lysosomes.", "localized in the lysosomes. the", "in the lysosomes. the death", "the lysosomes. the death domain", "lysosomes. the death domain of", "the death domain of tnfr1", "death domain of tnfr1 that", "domain of tnfr1 that is", "of tnfr1 that is responsible", "tnfr1 that is responsible for", "that is responsible for the", "is responsible for the initiation", "responsible for the initiation of", "for the initiation of the", "the initiation of the apoptotic", "initiation of the apoptotic pathway", "of the apoptotic pathway also", "the apoptotic pathway also mediates", "apoptotic pathway also mediates activation", "pathway also mediates activation of", "also mediates activation of an", "mediates activation of an acid", "activation of an acid smase.", "of an acid smase. the", "an acid smase. the two", "acid smase. the two proapoptotic", "smase. the two proapoptotic adaptor", "the two proapoptotic adaptor proteins", "two proapoptotic adaptor proteins tradd", "proapoptotic adaptor proteins tradd and", "adaptor proteins tradd and fadd", "proteins tradd and fadd are", "tradd and fadd are also", "and fadd are also involved", "fadd are also involved in", "are also involved in the", "also involved in the activation", "involved in the activation of", "in the activation of acid", "the activation of acid smase", "activation of acid smase signaling", "of acid smase signaling events", "smase signaling events schwandner", "signaling events schwandner r", "events schwandner r et", "schwandner r et al. 1998", "r et al. 1998 .", "et al. 1998 . tnf", "al. 1998 . tnf alpha", "1998 . tnf alpha can", ". tnf alpha can also", "tnf alpha can also activate", "alpha can also activate the", "can also activate the pro", "also activate the pro apoptotic", "the pro apoptotic acidic", "pro apoptotic acidic smase", "apoptotic acidic smase via", "acidic smase via caspase 8", "smase via caspase 8 mediated", "via caspase 8 mediated activation", "caspase 8 mediated activation of", "8 mediated activation of caspase", "mediated activation of caspase 7", "activation of caspase 7 which", "of caspase 7 which in", "caspase 7 which in turn", "7 which in turn proteolytically", "which in turn proteolytically cleaves", "in turn proteolytically cleaves and", "turn proteolytically cleaves and activates", "proteolytically cleaves and activates the", "cleaves and activates the 72kda", "and activates the 72kda pro", "activates the 72kda pro acid", "the 72kda pro acid smase", "72kda pro acid smase form", "acid smase form edelmann", "smase form edelmann b", "form edelmann b et", "edelmann b et al. 2011", "b et al. 2011 .", "et al. 2011 . neutral", "al. 2011 . neutral smase", "2011 . neutral smase smpd", "neutral smase smpd binds", "smase smpd binds to", "smpd binds to adaptor", "binds to adaptor protein nsmaf", "adaptor protein nsmaf fan", "fan which bridges", "which bridges it to nsmase", "bridges it to nsmase activating", "it to nsmase activating domain", "nsmase activating domain nsd", "domain nsd of", "of tnfr1 adam d", "tnfr1 adam d et", "adam d et al. 1996", "et al. 1996 adam", "al. 1996 adam klages", "1996 adam klages s", "et al. 1996 s\u00e9gui", "al. 1996 s\u00e9gui b", "1996 s\u00e9gui b et", "s\u00e9gui b et al. 2001", "b et al. 2001 .", "et al. 2001 . activation", "al. 2001 . activation of", "2001 . activation of smpd2", ". activation of smpd2 3", "activation of smpd2 3 leads", "of smpd2 3 leads to", "smpd2 3 leads to an", "3 leads to an accumulation", "leads to an accumulation of", "to an accumulation of ceramide", "an accumulation of ceramide at", "accumulation of ceramide at the", "of ceramide at the cell", "ceramide at the cell surface.

              ceramide", "at the cell surface.

              ceramide metabolism", "the cell surface.

              ceramide metabolism generates", "cell surface.

              ceramide metabolism generates a", "surface.

              ceramide metabolism generates a cascade", "metabolism generates a cascade of", "generates a cascade of bioactive", "a cascade of bioactive lipids", "of bioactive lipids all", "bioactive lipids all of", "lipids all of which", "all of which carry a", "of which carry a specific", "which carry a specific signaling", "carry a specific signaling capacity.", "a specific signaling capacity. ceramide", "specific signaling capacity. ceramide can", "signaling capacity. ceramide can be", "capacity. ceramide can be converted", "ceramide can be converted by", "can be converted by ceramidase", "be converted by ceramidase into", "converted by ceramidase into sphingosine", "ceramidase into sphingosine which", "into sphingosine which in", "sphingosine which in turn", "which in turn is phosphorylated", "in turn is phosphorylated by", "turn is phosphorylated by sphingosine", "is phosphorylated by sphingosine kinase", "phosphorylated by sphingosine kinase into", "by sphingosine kinase into sphingosine", "sphingosine kinase into sphingosine 1", "kinase into sphingosine 1 phosphate", "sphingosine 1 phosphate s1p", "1 phosphate s1p .", "phosphate s1p . these", "s1p . these lipids exert", ". these lipids exert opposite", "these lipids exert opposite biological", "lipids exert opposite biological effects:", "exert opposite biological effects: ceramide", "opposite biological effects: ceramide and", "biological effects: ceramide and sphingosine", "effects: ceramide and sphingosine are", "ceramide and sphingosine are able", "and sphingosine are able to", "sphingosine are able to induce", "are able to induce anti", "able to induce anti proliferative", "to induce anti proliferative and", "induce anti proliferative and pro", "anti proliferative and pro apoptotic", "proliferative and pro apoptotic responses", "pro apoptotic responses whereas", "apoptotic responses whereas s1p", "responses whereas s1p is", "whereas s1p is a cytoprotective", "s1p is a cytoprotective molecule", "is a cytoprotective molecule that", "a cytoprotective molecule that promotes", "cytoprotective molecule that promotes cell", "molecule that promotes cell growth", "that promotes cell growth and", "promotes cell growth and counteracts", "cell growth and counteracts apoptotic", "growth and counteracts apoptotic stimuli", "counteracts apoptotic stimuli cuvillier", "apoptotic stimuli cuvillier o", "stimuli cuvillier o et" ] }, { "record_id": "GLY_000594_1_1032", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5632681", "r hsa", "hsa 5632681", "r hsa 5632681" ] }, { "record_id": "GLY_000594_1_1032", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ligand receptor", "receptor interactions", "ligand receptor interactions", "repression of", "of hh", "hh signaling", "signaling in", "in the", "the absence", "absence of", "of ligand", "ligand depends", "depends on", "on the", "the transmembrane", "transmembrane receptor", "receptor protein", "protein patched", "which inhibits", "inhibits smoothened", "activity by", "by an", "an unknown", "unknown mechanism.", "mechanism. this", "this promotes", "promotes the", "the proteolytic", "proteolytic processing", "processing and/or", "and/or degradation", "degradation of", "of the", "the gli", "gli family", "family of", "of transcription", "transcription factors", "factors and", "and maintains", "maintains the", "the pathway", "pathway in", "in a", "a transcriptionally", "transcriptionally repressed", "repressed state", "reviewed in", "in briscoe", "briscoe and", "and therond", "2013 .", ". in", "ptch is", "is localized", "localized in", "the cilium", "while smo", "smo is", "is largely", "largely concentrated", "concentrated in", "in intracellular", "intracellular compartments.", "upon binding", "binding of", "hh to", "to the", "the ptch", "ptch receptor", "is endocytosed", "relieving smo", "smo inhibition", "inhibition and", "and allowing", "allowing it", "it to", "to accumulate", "accumulate in", "the primary", "primary cilium", "marigo et", "et al", "chen and", "and struhl", "stone et", "rohatgi et", "corbit et", "in goetz", "goetz and", "and anderson", "2010 .", "is activated", "activated by", "unknown mechanism", "allowing the", "the full", "full length", "length transcriptional", "transcriptional activator", "activator forms", "forms of", "gli proteins", "proteins to", "accumulate and", "and translocate", "translocate to", "the nucleus", "where they", "they bind", "bind to", "the promoters", "promoters of", "hh responsive", "responsive genes", ".
              in", "
              in addition", "addition to", "to ptch", "three additional", "additional membrane", "membrane proteins", "proteins have", "have been", "been shown", "shown to", "to bind", "bind hh", "hh and", "and to", "to be", "be required", "required for", "for hh", "hh dependent", "dependent signaling", "in vertebrates:", "vertebrates: cdon", "cam related/downregulated", "related/downregulated by", "by oncogenes", "brother of", "of cdo", "and gas1", "growth arrest", "arrest specific", "specific 1", "yao et", "okada et", "tenzen et", "mclellan et", "in kang", "kang et", "beachy et", "sanchez arrones", "arrones et", "2012 .", "cdon and", "and boc", "homologues of", "of drosophila", "drosophila ihog", "ihog and", "and boi", "boi respectively", "are evolutionarily", "evolutionarily conserved", "conserved transmembrane", "transmembrane glycoproteins", "glycoproteins that", "that have", "bind both", "both to", "to hh", "hh ligand", "ligand and", "the canonical", "canonical receptor", "receptor ptch", "ptch to", "to promote", "promote hh", "izzi et", "in sanchez", "despite the", "the evolutionary", "evolutionary conservation", "the mode", "mode of", "ligand binding", "binding by", "by cdon/ihog", "cdon/ihog and", "and boc/boi", "boc/boi is", "is distinct", "distinct in", "in vertebrates", "vertebrates and", "and invertebrates.", "high affinity", "affinity ligand", "by cdon", "boc requires", "requires ca2+", "while invertebrate", "invertebrate ligand", "binding is", "is heparin", "heparin dependent", "kavran et", ". gas1", "gas1 is", "is a", "a vertebrate", "vertebrate specific", "specific gpi", "gpi anchored", "anchored protein", "protein that", "that similarly", "similarly binds", "binds both", "receptor to", "martinelli and", "and fan", "2007 .", "boc and", "gas1 have", "have partially", "partially overlapping", "overlapping but", "but not", "not totally", "totally redundant", "redundant roles", "and knock", "knock out", "out of", "of all", "all three", "three is", "is required", "required to", "to abrogate", "abrogate hh", "in mice", "allen et", "repression of hh", "of hh signaling", "hh signaling in", "signaling in the", "in the absence", "the absence of", "absence of ligand", "of ligand depends", "ligand depends on", "depends on the", "on the transmembrane", "the transmembrane receptor", "transmembrane receptor protein", "receptor protein patched", "patched ptch", "which inhibits smoothened", "smoothened smo", "smo activity", "activity by an", "by an unknown", "an unknown mechanism.", "unknown mechanism. this", "mechanism. this promotes", "this promotes the", "promotes the proteolytic", "the proteolytic processing", "proteolytic processing and/or", "processing and/or degradation", "and/or degradation of", "degradation of the", "of the gli", "the gli family", "gli family of", "family of transcription", "of transcription factors", "transcription factors and", "factors and maintains", "and maintains the", "maintains the pathway", "the pathway in", "pathway in a", "in a transcriptionally", "a transcriptionally repressed", "transcriptionally repressed state", "state reviewed", "reviewed in briscoe", "in briscoe and", "briscoe and therond", "therond 2013", "2013 . in", ". in the", "ligand ptch", "ptch is localized", "is localized in", "localized in the", "in the cilium", "cilium while", "while smo is", "smo is largely", "is largely concentrated", "largely concentrated in", "concentrated in intracellular", "in intracellular compartments.", "compartments. upon", "upon binding of", "binding of hh", "of hh to", "hh to the", "to the ptch", "the ptch receptor", "ptch is endocytosed", "endocytosed relieving", "relieving smo inhibition", "smo inhibition and", "inhibition and allowing", "and allowing it", "allowing it to", "it to accumulate", "to accumulate in", "accumulate in the", "in the primary", "the primary cilium", "cilium marigo", "marigo et al", "al 1996", "1996 chen", "chen and struhl", "struhl 1996", "1996 stone", "stone et al", "1996 rohatgi", "rohatgi et al", "al 2007", "2007 corbit", "corbit et al", "al 2005", "2005 reviewed", "reviewed in goetz", "in goetz and", "goetz and anderson", "anderson 2010", "cilium smo", "smo is activated", "is activated by", "activated by an", "an unknown mechanism", "mechanism allowing", "allowing the full", "the full length", "full length transcriptional", "length transcriptional activator", "transcriptional activator forms", "activator forms of", "forms of the", "the gli proteins", "gli proteins to", "proteins to accumulate", "to accumulate and", "accumulate and translocate", "and translocate to", "translocate to the", "to the nucleus", "nucleus where", "where they bind", "they bind to", "bind to the", "to the promoters", "the promoters of", "promoters of hh", "of hh responsive", "hh responsive genes", "genes reviewed", "2013 .
              in", ".
              in addition", "
              in addition to", "addition to ptch", "ptch three", "three additional membrane", "additional membrane proteins", "membrane proteins have", "proteins have been", "have been shown", "been shown to", "shown to bind", "to bind hh", "bind hh and", "hh and to", "and to be", "to be required", "be required for", "required for hh", "for hh dependent", "hh dependent signaling", "dependent signaling in", "signaling in vertebrates:", "in vertebrates: cdon", "cdon cam", "cam related/downregulated by", "related/downregulated by oncogenes", "boc brother", "brother of cdo", "cdo and", "gas1 growth", "growth arrest specific", "arrest specific 1", "yao et al", "al 2006", "2006 okada", "okada et al", "2006 tenzen", "tenzen et al", "2006 mclellan", "mclellan et al", "al 2008", "2008 reviewed", "reviewed in kang", "in kang et", "kang et al", "2007 beachy", "beachy et al", "al 2010", "2010 sanchez", "sanchez arrones et", "arrones et al", "al 2012", ". cdon", "cdon and boc", "boc homologues", "homologues of drosophila", "of drosophila ihog", "drosophila ihog and", "ihog and boi", "and boi respectively", "respectively are", "are evolutionarily conserved", "evolutionarily conserved transmembrane", "conserved transmembrane glycoproteins", "transmembrane glycoproteins that", "glycoproteins that have", "that have been", "to bind both", "bind both to", "both to hh", "to hh ligand", "hh ligand and", "ligand and to", "and to the", "to the canonical", "the canonical receptor", "canonical receptor ptch", "receptor ptch to", "ptch to promote", "to promote hh", "promote hh signaling", "signaling okada", "2006 yao", "2008 izzi", "izzi et al", "al 2011", "2011 reviewed", "reviewed in sanchez", "in sanchez arrones", ". despite", "despite the evolutionary", "the evolutionary conservation", "conservation the", "the mode of", "mode of ligand", "of ligand binding", "ligand binding by", "binding by cdon/ihog", "by cdon/ihog and", "cdon/ihog and boc/boi", "and boc/boi is", "boc/boi is 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not", "but not totally", "not totally redundant", "totally redundant roles", "roles and", "and knock out", "knock out of", "out of all", "of all three", "all three is", "three is required", "is required to", "required to abrogate", "to abrogate hh", "abrogate hh signaling", "signaling in mice", "mice allen", "allen et al", "2011 izzi", "repression of hh signaling", "of hh signaling in", "hh signaling in the", "signaling in the absence", "in the absence of", "the absence of ligand", "absence of ligand depends", "of ligand depends on", "ligand depends on the", "depends on the transmembrane", "on the transmembrane receptor", "the transmembrane receptor protein", "transmembrane receptor protein patched", "protein patched ptch", "ptch which", "inhibits smoothened smo", "smo activity by", "activity by an unknown", "by an unknown mechanism.", "an unknown mechanism. this", "unknown mechanism. this promotes", "mechanism. this promotes the", "this promotes the proteolytic", "promotes the proteolytic processing", "the proteolytic processing and/or", "proteolytic processing and/or degradation", "processing and/or degradation of", "and/or degradation of the", "degradation of the gli", "of the gli family", "the gli family of", "gli family of transcription", "family of transcription factors", "of transcription factors and", "transcription factors and maintains", "factors and maintains the", "and maintains the pathway", "maintains the pathway in", "the pathway in a", "pathway in a transcriptionally", "in a transcriptionally repressed", "a transcriptionally repressed state", "repressed state reviewed", "state reviewed in", "reviewed in briscoe and", "in briscoe and therond", "and therond 2013", "therond 2013 .", "2013 . in the", ". in the absence", "of ligand ptch", "ligand ptch is", "ptch is localized in", "is localized in the", "localized in the cilium", "the cilium while", "cilium while smo", "while smo is largely", "smo is largely concentrated", "is largely concentrated in", "largely concentrated in intracellular", "concentrated in intracellular compartments.", "intracellular compartments. upon", "compartments. upon binding", "upon binding of hh", "binding of hh to", "of hh to the", "hh to the ptch", "to the ptch receptor", "ptch receptor ptch", "receptor ptch is", "is endocytosed relieving", "endocytosed relieving smo", "relieving smo inhibition and", "smo inhibition and allowing", "inhibition and allowing it", "and allowing it to", "allowing it to accumulate", "it to accumulate in", "to accumulate in the", "accumulate in the primary", "in the primary cilium", "primary cilium marigo", "cilium marigo et", "et al 1996", "1996 chen and", "and struhl 1996", "1996 stone et", "1996 rohatgi et", "et al 2007", "2007 corbit et", "et al 2005", "2005 reviewed in", "reviewed in goetz and", "in goetz and anderson", "and anderson 2010", "anderson 2010 .", "2010 . in", "the cilium smo", "cilium smo is", "smo is activated by", "is activated by an", "activated by an unknown", "by an unknown mechanism", "unknown mechanism allowing", "mechanism allowing the", "allowing the full length", "the full length transcriptional", "full length transcriptional activator", "length transcriptional activator forms", "transcriptional activator forms of", "activator forms of the", "forms of the gli", "of the gli proteins", "the gli proteins to", "gli proteins to accumulate", "proteins to accumulate and", "to accumulate and translocate", "accumulate and translocate to", "and translocate to the", "translocate to the nucleus", "the nucleus where", "nucleus where they", "where they bind to", "they bind to the", "bind to the promoters", "to the promoters of", "the promoters of hh", "promoters of hh responsive", "of hh responsive genes", "responsive genes reviewed", "genes reviewed in", "2013 .
              in addition", ".
              in addition to", "
              in addition to ptch", "to ptch three", "ptch three additional", "three additional membrane proteins", "additional membrane proteins have", "membrane proteins have been", "proteins have been shown", "have been shown to", "been shown to bind", "shown to bind hh", "to bind hh and", "bind hh and to", "hh and to be", "and to be required", "to be required for", "be required for hh", "required for hh dependent", "for hh dependent signaling", "hh dependent signaling in", "dependent signaling in vertebrates:", "signaling in vertebrates: cdon", "vertebrates: cdon cam", "cdon cam related/downregulated", "cam related/downregulated by oncogenes", "oncogenes boc", "boc brother of", "of cdo and", "cdo and gas1", "and gas1 growth", "gas1 growth arrest", "growth arrest specific 1", "1 yao", "et al 2006", "2006 okada et", "2006 tenzen et", "2006 mclellan et", "et al 2008", "2008 reviewed in", "reviewed in kang et", "in kang et al", "2007 beachy et", "et al 2010", "2010 sanchez arrones", "sanchez arrones et al", "et al 2012", "al 2012 .", "2012 . cdon", ". cdon and", "and boc homologues", "boc homologues of", "homologues of drosophila ihog", "of drosophila ihog and", "drosophila ihog and boi", "ihog and boi respectively", "boi respectively are", "respectively are evolutionarily", "are evolutionarily conserved transmembrane", "evolutionarily conserved transmembrane glycoproteins", "conserved transmembrane glycoproteins that", "transmembrane glycoproteins that have", "glycoproteins that have been", "that have been shown", "shown to bind both", "to bind both to", "bind both to hh", "both to hh ligand", "to hh ligand and", "hh ligand and to", "ligand and to the", "and to the canonical", "to the canonical receptor", "the canonical receptor ptch", "canonical receptor ptch to", "receptor ptch to promote", "ptch to promote hh", "to promote hh signaling", "hh signaling okada", "signaling okada et", "2006 yao et", "2008 izzi et", "et al 2011", "2011 reviewed in", "reviewed in sanchez arrones", "in sanchez arrones et", "2012 . despite", ". despite the", "despite the evolutionary conservation", "evolutionary conservation the", "conservation the mode", "the mode of ligand", "mode of ligand binding", "of ligand binding by", "ligand binding by cdon/ihog", "binding by cdon/ihog and", "by cdon/ihog and boc/boi", "cdon/ihog and boc/boi is", "and boc/boi is distinct", "boc/boi is distinct in", "is distinct in vertebrates", "distinct in vertebrates and", "in vertebrates and invertebrates.", "and invertebrates. high", "invertebrates. high affinity", "high affinity ligand binding", "affinity ligand binding by", "ligand binding by cdon", "binding by cdon and", "by cdon and boc", "cdon and boc requires", "and boc requires ca2+", "requires ca2+ while", "ca2+ while invertebrate", "while invertebrate ligand binding", "invertebrate ligand binding is", "ligand binding is heparin", "binding is heparin dependent", "heparin dependent okada", "dependent okada et", "2008 yao et", "2006 kavran et", "al 2010 .", "2010 . gas1 is", ". gas1 is a", "gas1 is a vertebrate", "is a vertebrate specific", "a vertebrate specific gpi", "vertebrate specific gpi anchored", "specific gpi anchored protein", "gpi anchored protein that", "anchored protein that similarly", "protein that similarly binds", "that similarly binds both", "similarly binds both to", "binds both to hh", "and to the ptch", "the ptch receptor to", "ptch receptor to promote", "receptor to promote hh", "hh signaling martinelli", "signaling martinelli and", "and fan 2007", "2007 izzi et", "al 2007 .", "2007 . cdon", "cdon boc and", "boc and gas1 have", "and gas1 have partially", "gas1 have partially overlapping", "have partially overlapping but", "partially overlapping but not", "overlapping but not totally", "but not totally redundant", "not totally redundant roles", "redundant roles and", "roles and knock", "and knock out of", "knock out of all", "out of all three", "of all three is", "all three is required", "three is required to", "is required to abrogate", "required to abrogate hh", "to abrogate hh signaling", "abrogate hh signaling in", "hh signaling in mice", "in mice allen", "mice allen et", "2011 izzi et", "repression of hh signaling in", "of hh signaling in the", "hh signaling in the absence", "signaling in the absence of", "in the absence of ligand", "the absence of ligand depends", "absence of ligand depends on", "of ligand depends on the", "ligand depends on the transmembrane", "depends on the transmembrane receptor", "on the transmembrane receptor protein", "the transmembrane receptor protein patched", "receptor protein patched ptch", "ptch which inhibits", "which inhibits smoothened smo", "smoothened smo activity", "smo activity by an", "activity by an unknown mechanism.", "by an unknown mechanism. this", "an unknown mechanism. this promotes", "unknown mechanism. this promotes the", "mechanism. this promotes the proteolytic", "this promotes the proteolytic processing", "promotes the proteolytic processing and/or", "the proteolytic processing and/or degradation", "proteolytic processing and/or degradation of", "processing and/or degradation of the", "and/or degradation of the gli", "degradation of the gli family", "of the gli family of", "the gli family of transcription", "gli family of transcription factors", "family of transcription factors and", "of transcription factors and maintains", "transcription factors and maintains the", "factors and maintains the pathway", "and maintains the pathway in", "maintains the pathway in a", "the pathway in a transcriptionally", "pathway in a transcriptionally repressed", "in a transcriptionally repressed state", "transcriptionally repressed state reviewed", "repressed state reviewed in", "state reviewed in briscoe", "reviewed in briscoe and therond", "briscoe and therond 2013", "and therond 2013 .", "therond 2013 . in", "2013 . in the absence", ". in the absence of", "absence of ligand ptch", "of ligand ptch is", "ligand ptch is localized", "ptch is localized in the", "is localized in the cilium", "in the cilium while", "the cilium while smo", "cilium while smo is", "while smo is largely concentrated", "smo is largely concentrated in", "is largely concentrated in intracellular", "largely concentrated in intracellular compartments.", "in intracellular compartments. upon", "intracellular compartments. upon binding", "compartments. upon binding of", "upon binding of hh to", "binding of hh to the", "of hh to the ptch", "hh to the ptch receptor", "the ptch receptor ptch", "ptch receptor ptch is", "receptor ptch is endocytosed", "ptch is endocytosed relieving", "is endocytosed relieving smo", "endocytosed relieving smo inhibition", "relieving smo inhibition and allowing", "smo inhibition and allowing it", "inhibition and allowing it to", "and allowing it to accumulate", "allowing it to accumulate in", "it to accumulate in the", "to accumulate in the primary", "accumulate in the primary cilium", "the primary cilium marigo", "primary cilium marigo et", "cilium marigo et al", "marigo et al 1996", "al 1996 chen", "1996 chen and struhl", "chen and struhl 1996", "struhl 1996 stone", "1996 stone et al", "stone et al 1996", "al 1996 rohatgi", "1996 rohatgi et al", "rohatgi et al 2007", "al 2007 corbit", "2007 corbit et al", "corbit et al 2005", "al 2005 reviewed", "2005 reviewed in goetz", "reviewed in goetz and anderson", "goetz and anderson 2010", "and anderson 2010 .", "2010 . in the", ". in the cilium", "in the cilium smo", "the cilium smo is", "cilium smo is activated", "smo is activated by an", "is activated by an unknown", "activated by an unknown mechanism", "an unknown mechanism allowing", "unknown mechanism allowing the", "mechanism allowing the full", "allowing the full length transcriptional", "the full length transcriptional activator", "full length transcriptional activator forms", "length transcriptional activator forms of", "transcriptional activator forms of the", "activator forms of the gli", "forms of the gli proteins", "of the gli proteins to", "the gli proteins to accumulate", "gli proteins to accumulate and", "proteins to accumulate and translocate", "to accumulate and translocate to", "accumulate and translocate to the", "and translocate to the nucleus", "to the nucleus where", "the nucleus where they", "nucleus where they bind", "where they bind to the", "they bind to the promoters", "bind to the promoters of", "to the promoters of hh", "the promoters of hh responsive", "promoters of hh responsive genes", "hh responsive genes reviewed", "responsive genes reviewed in", "genes reviewed in briscoe", "therond 2013 .
              in", "2013 .
              in addition to", ".
              in addition to ptch", "addition to ptch three", "to ptch three additional", "ptch three additional membrane", "three additional membrane proteins have", "additional membrane proteins have been", "membrane proteins have been shown", "proteins have been shown to", "have been shown to bind", "been shown to bind hh", "shown to bind hh and", "to bind hh and to", "bind hh and to be", "hh and to be required", "and to be required for", "to be required for hh", "be required for hh dependent", "required for hh dependent signaling", "for hh dependent signaling in", "hh dependent signaling in vertebrates:", "dependent signaling in vertebrates: cdon", "in vertebrates: cdon cam", "vertebrates: cdon cam related/downregulated", "cdon cam related/downregulated by", "by oncogenes boc", "boc brother of cdo", "brother of cdo and", "of cdo and gas1", "and gas1 growth arrest", "gas1 growth arrest specific", "specific 1 yao", "1 yao et", "yao et al 2006", "al 2006 okada", "2006 okada et al", "okada et al 2006", "al 2006 tenzen", "2006 tenzen et al", "tenzen et al 2006", "al 2006 mclellan", "2006 mclellan et al", "mclellan et al 2008", "al 2008 reviewed", "2008 reviewed in kang", "reviewed in kang et al", "kang et al 2007", "al 2007 beachy", "2007 beachy et al", "beachy et al 2010", "al 2010 sanchez", "2010 sanchez arrones et", "arrones et al 2012", "et al 2012 .", "2012 . cdon and", ". cdon and boc", "cdon and boc homologues", "and boc homologues of", "boc homologues of drosophila", "homologues of drosophila ihog and", "of drosophila ihog and boi", "drosophila ihog and boi respectively", "and boi respectively are", "boi respectively are evolutionarily", "respectively are evolutionarily conserved", "are evolutionarily conserved transmembrane glycoproteins", "evolutionarily conserved transmembrane glycoproteins that", "conserved transmembrane glycoproteins that have", "transmembrane glycoproteins that have been", "glycoproteins that have been shown", "that have been shown to", "been shown to bind both", "shown to bind both to", "to bind both to hh", "bind both to hh ligand", "both to hh ligand and", "to hh ligand and to", "hh ligand and to the", "ligand and to the canonical", "and to the canonical receptor", "to the canonical receptor ptch", "the canonical receptor ptch to", "canonical receptor ptch to promote", "receptor ptch to promote hh", "ptch to promote hh signaling", "promote hh signaling okada", "hh signaling okada et", "signaling okada et al", "al 2006 yao", "2006 yao et al", "al 2008 izzi", "2008 izzi et al", "izzi et al 2011", "al 2011 reviewed", "2011 reviewed in sanchez", "reviewed in sanchez arrones et", "in sanchez arrones et al", "2012 . despite the", ". despite the evolutionary", "the evolutionary conservation the", "evolutionary conservation the mode", "conservation the mode of", "the mode of ligand binding", "mode of ligand binding by", "of ligand binding by cdon/ihog", "ligand binding by cdon/ihog and", "binding by cdon/ihog and boc/boi", "by cdon/ihog and boc/boi is", "cdon/ihog and boc/boi is distinct", "and boc/boi is distinct in", "boc/boi is distinct in vertebrates", "is distinct in vertebrates and", "distinct in vertebrates and invertebrates.", "vertebrates and invertebrates. high", "and invertebrates. high affinity", "invertebrates. high affinity ligand", "high affinity ligand binding by", "affinity ligand binding by cdon", "ligand binding by cdon and", "binding by cdon and boc", "by cdon and boc requires", "cdon and boc requires ca2+", "boc requires ca2+ while", "requires ca2+ while invertebrate", "ca2+ while invertebrate ligand", "while invertebrate ligand binding is", "invertebrate ligand binding is heparin", "ligand binding is heparin dependent", "is heparin dependent okada", "heparin dependent okada et", "dependent okada et al", "al 2008 yao", "2008 yao et al", "al 2006 kavran", "2006 kavran et al", "kavran et al 2010", "et al 2010 .", "al 2010 . gas1", "2010 . gas1 is a", ". gas1 is a vertebrate", "gas1 is a vertebrate specific", "is a vertebrate specific gpi", "a vertebrate specific gpi anchored", "vertebrate specific gpi anchored protein", "specific gpi anchored protein that", "gpi anchored protein that similarly", "anchored protein that similarly binds", "protein that similarly binds both", "that similarly binds both to", "similarly binds both to hh", "binds both to hh ligand", "ligand and to the ptch", "and to the ptch receptor", "to the ptch receptor to", "the ptch receptor to promote", "ptch receptor to promote hh", "receptor to promote hh signaling", "promote hh signaling martinelli", "hh signaling martinelli and", "signaling martinelli and fan", "martinelli and fan 2007", "fan 2007 izzi", "2007 izzi et al", "2011 reviewed in kang", "et al 2007 .", ". cdon boc", "cdon boc and gas1", "boc and gas1 have partially", "and gas1 have partially overlapping", "gas1 have partially overlapping but", "have partially overlapping but not", "partially overlapping but not totally", "overlapping but not totally redundant", "but not totally redundant roles", "totally redundant roles and", "redundant roles and knock", "roles and knock out", "and knock out of all", "knock out of all three", "out of all three is", "of all three is required", "all three is required to", "three is required to abrogate", "is required to abrogate hh", "required to abrogate hh signaling", "to abrogate hh signaling in", "abrogate hh signaling in mice", "signaling in mice allen", "in mice allen et", "mice allen et al", "allen et al 2011", "al 2011 izzi", "2011 izzi et al", "2011 reviewed in briscoe" ] }, { "record_id": "GLY_000594_1_1033", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5637810", "r hsa", "hsa 5637810", "r hsa 5637810" ] }, { "record_id": "GLY_000594_1_1033", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "constitutive signaling", "signaling by", "by egfrviii", "constitutive signaling by", "signaling by egfrviii", "constitutive signaling by egfrviii", "in glioblastoma", "the most", "most prevalent", "prevalent egfr", "egfr mutation", "present in", "in ~25%", "~25% of", "of tumors", "is the", "the deletion", "deletion of", "of the", "the ligand", "ligand binding", "binding domain", "domain of", "of egfr", "accompanied with", "with amplification", "amplification of", "the mutated", "mutated allele", "which results", "results in", "in over", "over expression", "expression of", "the mutant", "mutant protein", "protein known", "known as", "as egfrviii.", "egfrviii. egfrviii", "egfrviii mutant", "mutant is", "is not", "not able", "able to", "to bind", "bind a", "a ligand", "but dimerizes", "dimerizes and", "and autophosphorylates", "autophosphorylates spontaneously", "spontaneously and", "and is", "is therefore", "therefore constitutively", "constitutively active", "fernandes et", "et al.", "al. 2001", "2001 .", ". point", "point mutations", "mutations in", "in the", "the extracellular", "extracellular domain", "egfr are", "are also", "also frequently", "frequently found", "found in", "but ligand", "binding ability", "ability and", "and responsiveness", "responsiveness are", "are preserved", "lee et", "al. 2006", "2006 .", ".
              similar", "
              similar to", "to egfr", "egfr kinase", "kinase domain", "domain mutants", "mutant needs", "needs to", "to maintain", "maintain association", "association with", "with the", "the chaperone", "chaperone heat", "heat shock", "shock protein", "protein 90", "for proper", "proper functioning", "shimamura et", "al. 2005", "lavictoire et", "al. 2003", "2003 .", ". cdc37", "cdc37 is", "is a", "a co", "co chaperone", "chaperone of", "of hsp90", "hsp90 that", "that acts", "acts as", "as a", "a scaffold", "scaffold and", "and regulator", "regulator of", "of interaction", "interaction between", "between hsp90", "hsp90 and", "and its", "its protein", "protein kinase", "kinase clients.", "clients. cdc37", "is frequently", "frequently over", "over expressed", "expressed in", "in cancers", "cancers involving", "involving mutant", "mutant kinases", "kinases and", "and acts", "as an", "an oncogene", "roe et", "al. 2004", "reviewed by", "by gray", "gray jr.", "jr. et", "al. 2008", "2008 .", ".
              expression", "
              expression of", "of egfrviii", "mutant results", "in aberrant", "aberrant activation", "activation of", "of downstream", "downstream signaling", "signaling cascades", "namely ras/raf/map", "ras/raf/map kinase", "kinase signaling", "signaling and", "and pi3k/akt", "pi3k/akt signaling", "and possibly", "possibly signaling", "by plcg1", "which leads", "leads to", "to increased", "increased cell", "cell proliferation", "proliferation and", "and survival", "providing selective", "selective advantage", "advantage to", "to cancer", "cancer cells", "cells that", "that harbor", "harbor egfrviii", "huang et", "al. 2007", "2007 .", ".
              ", "
              egfrviii", "mutant does", "does not", "not autophosorylate", "autophosorylate on", "on the", "the tyrosine", "tyrosine residue", "residue y1069", "i.e. y1045", "y1045 in", "the mature", "mature protein", "a docking", "docking site", "site for", "for cbl", "therefore unable", "unable to", "to recruit", "recruit cbl", "cbl ubiquitin", "ubiquitin ligase", "which enables", "enables it", "it to", "to escape", "escape degradation", "han et", "glioblastoma the", "the most prevalent", "most prevalent egfr", "prevalent egfr mutation", "mutation present", "present in ~25%", "in ~25% of", "~25% of tumors", "tumors is", "is the deletion", "the deletion of", "deletion of the", "of the ligand", "the ligand binding", "ligand binding domain", "binding domain of", "domain of egfr", "egfr accompanied", "accompanied with amplification", "with amplification of", "amplification of the", "of the mutated", "the mutated allele", "allele which", "which results in", "results in over", "in over expression", "over expression of", "expression of the", "of the mutant", "the mutant protein", "mutant protein known", "protein known as", "known as egfrviii.", "as egfrviii. egfrviii", "egfrviii. egfrviii mutant", "egfrviii mutant is", "mutant is not", "is not able", "not able to", "able to bind", "to bind a", "bind a ligand", "ligand but", "but dimerizes and", "dimerizes and autophosphorylates", "and autophosphorylates spontaneously", "autophosphorylates spontaneously and", "spontaneously and is", "and is therefore", "is therefore constitutively", "therefore constitutively active", "active fernandes", "fernandes et al.", "et al. 2001", "al. 2001 .", "2001 . point", ". point mutations", "point mutations in", "mutations in the", "in the extracellular", "the extracellular domain", "extracellular domain of", "of egfr are", "egfr are also", "are also frequently", "also frequently found", "frequently found in", "found in glioblastoma", "glioblastoma but", "but ligand binding", "ligand binding ability", "binding ability and", "ability and responsiveness", "and responsiveness are", "responsiveness are preserved", "preserved lee", "lee et al.", "et al. 2006", "al. 2006 .", "2006 .
              similar", ".
              similar to", "
              similar to egfr", "to egfr kinase", "egfr kinase domain", "kinase domain mutants", "mutants egfrviii", "egfrviii mutant needs", "mutant needs to", "needs to maintain", "to maintain association", "maintain association with", "association with the", "with the chaperone", "the chaperone heat", "chaperone heat shock", "heat shock protein", "shock protein 90", "90 hsp90", "hsp90 for", "for proper functioning", "functioning shimamura", "shimamura et al.", "et al. 2005", "2005 lavictoire", "lavictoire et al.", "et al. 2003", "al. 2003 .", "2003 . cdc37", ". cdc37 is", "cdc37 is a", "is a co", "a co chaperone", "co chaperone of", "chaperone of hsp90", "of hsp90 that", "hsp90 that acts", "that acts as", "acts as a", "as a scaffold", "a scaffold and", "scaffold and regulator", "and regulator of", "regulator of interaction", "of interaction between", "interaction between hsp90", "between hsp90 and", "hsp90 and its", "and its protein", "its protein kinase", "protein kinase clients.", "kinase clients. cdc37", "clients. cdc37 is", "cdc37 is frequently", "is frequently over", "frequently over expressed", "over expressed in", "expressed in cancers", "in cancers involving", "cancers involving mutant", "involving mutant kinases", "mutant kinases and", "kinases and acts", "and acts as", "acts as an", "as an oncogene", "oncogene roe", "roe et al.", "et al. 2004", "2004 reviewed", "reviewed by gray", "by gray jr.", "gray jr. et", "jr. et al.", "et al. 2008", "al. 2008 .", "2008 .
              expression", ".
              expression of", "
              expression of egfrviii", "of egfrviii mutant", "egfrviii mutant results", "mutant results in", "results in aberrant", "in aberrant activation", "aberrant activation of", "activation of downstream", "of downstream signaling", "downstream signaling cascades", "cascades namely", "namely ras/raf/map kinase", "ras/raf/map kinase signaling", "kinase signaling and", "signaling and pi3k/akt", "and pi3k/akt signaling", "and possibly signaling", "possibly signaling by", "signaling by plcg1", "plcg1 which", "which leads to", "leads to increased", "to increased cell", "increased cell proliferation", "cell proliferation and", "proliferation and survival", "survival providing", "providing selective advantage", "selective advantage to", "advantage to cancer", "to cancer cells", "cancer cells that", "cells that harbor", "that harbor egfrviii", "egfrviii huang", "huang et al.", "et al. 2007", "al. 2007 .", "2007 .
              ", ".
              egfrviii", "
              egfrviii mutant", "egfrviii mutant does", "mutant does not", "does not autophosorylate", "not autophosorylate on", "autophosorylate on the", "on the tyrosine", "the tyrosine residue", "tyrosine residue y1069", "y1069 i.e.", "i.e. y1045 in", "y1045 in the", "in the mature", "the mature protein", "a docking site", "docking site for", "site for cbl", "cbl and", "is therefore unable", "therefore unable to", "unable to recruit", "to recruit cbl", "recruit cbl ubiquitin", "cbl ubiquitin ligase", "ligase which", "which enables it", "enables it to", "it to escape", "to escape degradation", "degradation han", "han et al.", "in glioblastoma the", "glioblastoma the most", "the most prevalent egfr", "most prevalent egfr mutation", "egfr mutation present", "mutation present in", "present in ~25% of", "in ~25% of tumors", "of tumors is", "tumors is the", "is the deletion of", "the deletion of the", "deletion of the ligand", "of the ligand binding", "the ligand binding domain", "ligand binding domain of", "binding domain of egfr", "of egfr accompanied", "egfr accompanied with", "accompanied with amplification of", "with amplification of the", "amplification of the mutated", "of the mutated allele", "mutated allele which", "allele which results", "which results in over", "results in over expression", "in over expression of", "over expression of the", "expression of the mutant", "of the mutant protein", "the mutant protein known", "mutant protein known as", "protein known as egfrviii.", "known as egfrviii. egfrviii", "as egfrviii. egfrviii mutant", "egfrviii. egfrviii mutant is", "egfrviii mutant is not", "mutant is not able", "is not able to", "not able to bind", "able to bind a", "to bind a ligand", "a ligand but", "ligand but dimerizes", "but dimerizes and autophosphorylates", "dimerizes and autophosphorylates spontaneously", "and autophosphorylates spontaneously and", "autophosphorylates spontaneously and is", "spontaneously and is therefore", "and is therefore constitutively", "is therefore constitutively active", "constitutively active fernandes", "active fernandes et", "fernandes et al. 2001", "et al. 2001 .", "al. 2001 . point", "2001 . point mutations", ". point mutations in", "point mutations in the", "mutations in the extracellular", "in the extracellular domain", "the extracellular domain of", "extracellular domain of egfr", "domain of egfr are", "of egfr are also", "egfr are also frequently", "are also frequently found", "also frequently found in", "frequently found in glioblastoma", "in glioblastoma but", "glioblastoma but ligand", "but ligand binding ability", "ligand binding ability and", "binding ability and responsiveness", "ability and responsiveness are", "and responsiveness are preserved", "are preserved lee", "preserved lee et", "lee et al. 2006", "et al. 2006 .", "al. 2006 .
              similar", "2006 .
              similar to", ".
              similar to egfr", "
              similar to egfr kinase", "to egfr kinase domain", "egfr kinase domain mutants", "domain mutants egfrviii", "mutants egfrviii mutant", "egfrviii mutant needs to", "mutant needs to maintain", "needs to maintain association", "to maintain association with", "maintain association with the", "association with the chaperone", "with the chaperone heat", "the chaperone heat shock", "chaperone heat shock protein", "heat shock protein 90", "protein 90 hsp90", "hsp90 for proper", "proper functioning shimamura", "functioning shimamura et", "shimamura et al. 2005", "al. 2005 lavictoire", "2005 lavictoire et", "lavictoire et al. 2003", "et al. 2003 .", "al. 2003 . cdc37", "2003 . cdc37 is", ". cdc37 is a", "cdc37 is a co", "is a co chaperone", "a co chaperone of", "co chaperone of hsp90", "chaperone of hsp90 that", "of hsp90 that acts", "hsp90 that acts as", "that acts as a", "acts as a scaffold", "as a scaffold and", "a scaffold and regulator", "scaffold and regulator of", "and regulator of interaction", "regulator of interaction between", "of interaction between hsp90", "interaction between hsp90 and", "between hsp90 and its", "hsp90 and its protein", "and its protein kinase", "its protein kinase clients.", "protein kinase clients. cdc37", "kinase clients. cdc37 is", "clients. cdc37 is frequently", "cdc37 is frequently over", "is frequently over expressed", "frequently over expressed in", "over expressed in cancers", "expressed in cancers involving", "in cancers involving mutant", "cancers involving mutant kinases", "involving mutant kinases and", "mutant kinases and acts", "kinases and acts as", "and acts as an", "acts as an oncogene", "an oncogene roe", "oncogene roe et", "roe et al. 2004", "al. 2004 reviewed", "2004 reviewed by", "reviewed by gray jr.", "by gray jr. et", "gray jr. et al.", "jr. et al. 2008", "et al. 2008 .", "al. 2008 .
              expression", "2008 .
              expression of", ".
              expression of egfrviii", "
              expression of egfrviii mutant", "of egfrviii mutant results", "egfrviii mutant results in", "mutant results in aberrant", "results in aberrant activation", "in aberrant activation of", "aberrant activation of downstream", "activation of downstream signaling", "of downstream signaling cascades", "signaling cascades namely", "cascades namely ras/raf/map", "namely ras/raf/map kinase signaling", "ras/raf/map kinase signaling and", "kinase signaling and pi3k/akt", "signaling and pi3k/akt signaling", "pi3k/akt signaling and", "signaling and possibly", "and possibly signaling by", "possibly signaling by plcg1", "by plcg1 which", "plcg1 which leads", "which leads to increased", "leads to increased cell", "to increased cell proliferation", "increased cell proliferation and", "cell proliferation and survival", "and survival providing", "survival providing selective", "providing selective advantage to", "selective advantage to cancer", "advantage to cancer cells", "to cancer cells that", "cancer cells that harbor", "cells that harbor egfrviii", "harbor egfrviii huang", "egfrviii huang et", "huang et al. 2007", "et al. 2007 .", "al. 2007 .
              ", "2007 .
              egfrviii", ".
              egfrviii mutant", "
              egfrviii mutant does", "egfrviii mutant does not", "mutant does not autophosorylate", "does not autophosorylate on", "not autophosorylate on the", "autophosorylate on the tyrosine", "on the tyrosine residue", "the tyrosine residue y1069", "residue y1069 i.e.", "y1069 i.e. y1045", "i.e. y1045 in the", "y1045 in the mature", "in the mature protein", "protein a", "a docking site for", "docking site for cbl", "for cbl and", "cbl and is", "and is therefore unable", "is therefore unable to", "therefore unable to recruit", "unable to recruit cbl", "to recruit cbl ubiquitin", "recruit cbl ubiquitin ligase", "ubiquitin ligase which", "ligase which enables", "which enables it to", "enables it to escape", "it to escape degradation", "escape degradation han", "degradation han et", "han et al. 2006", "in glioblastoma the most", "glioblastoma the most prevalent", "the most prevalent egfr mutation", "prevalent egfr mutation present", "egfr mutation present in", "mutation present in ~25%", "present in ~25% of tumors", "~25% of tumors is", "of tumors is the", "tumors is the deletion", "is the deletion of the", "the deletion of the ligand", "deletion of the ligand binding", "of the ligand binding domain", "the ligand binding domain of", "ligand binding domain of egfr", "domain of egfr accompanied", "of egfr accompanied with", "egfr accompanied with amplification", "accompanied with amplification of the", "with amplification of the mutated", "amplification of the mutated allele", "the mutated allele which", "mutated allele which results", "allele which results in", "which results in over expression", "results in over expression of", "in over expression of the", "over expression of the mutant", "expression of the mutant protein", "of the mutant protein known", "the mutant protein known as", "mutant protein known as egfrviii.", "protein known as egfrviii. egfrviii", "known as egfrviii. egfrviii mutant", "as egfrviii. egfrviii mutant is", "egfrviii. egfrviii mutant is not", "egfrviii mutant is not able", "mutant is not able to", "is not able to bind", "not able to bind a", "able to bind a ligand", "bind a ligand but", "a ligand but dimerizes", "ligand but dimerizes and", "but dimerizes and autophosphorylates spontaneously", "dimerizes and autophosphorylates spontaneously and", "and autophosphorylates spontaneously and is", "autophosphorylates spontaneously and is therefore", "spontaneously and is therefore constitutively", "and is therefore constitutively active", "therefore constitutively active fernandes", "constitutively active fernandes et", "active fernandes et al.", "fernandes et al. 2001 .", "et al. 2001 . point", "al. 2001 . point mutations", "2001 . point mutations in", ". point mutations in the", "point mutations in the extracellular", "mutations in the extracellular domain", "in the extracellular domain of", "the extracellular domain of egfr", "extracellular domain of egfr are", "domain of egfr are also", "of egfr are also frequently", "egfr are also frequently found", "are also frequently found in", "also frequently found in glioblastoma", "found in glioblastoma but", "in glioblastoma but ligand", "glioblastoma but ligand binding", "but ligand binding ability and", "ligand binding ability and responsiveness", "binding ability and responsiveness are", "ability and responsiveness are preserved", "responsiveness are preserved lee", "are preserved lee et", "preserved lee et al.", "lee et al. 2006 .", "et al. 2006 .
              similar", "al. 2006 .
              similar to", "2006 .
              similar to egfr", ".
              similar to egfr kinase", "
              similar to egfr kinase domain", "to egfr kinase domain mutants", "kinase domain mutants egfrviii", "domain mutants egfrviii mutant", "mutants egfrviii mutant needs", "egfrviii mutant needs to maintain", "mutant needs to maintain association", "needs to maintain association with", "to maintain association with the", "maintain association with the chaperone", "association with the chaperone heat", "with the chaperone heat shock", "the chaperone heat shock protein", "chaperone heat shock protein 90", "shock protein 90 hsp90", "90 hsp90 for", "hsp90 for proper functioning", "for proper functioning shimamura", "proper functioning shimamura et", "functioning shimamura et al.", "et al. 2005 lavictoire", "al. 2005 lavictoire et", "2005 lavictoire et al.", "lavictoire et al. 2003 .", "et al. 2003 . cdc37", "al. 2003 . cdc37 is", "2003 . cdc37 is a", ". cdc37 is a co", "cdc37 is a co chaperone", "is a co chaperone of", "a co chaperone of hsp90", "co chaperone of hsp90 that", "chaperone of hsp90 that acts", "of hsp90 that acts as", "hsp90 that acts as a", "that acts as a scaffold", "acts as a scaffold and", "as a scaffold and regulator", "a scaffold and regulator of", "scaffold and regulator of interaction", "and regulator of interaction between", "regulator of interaction between hsp90", "of interaction between hsp90 and", "interaction between hsp90 and its", "between hsp90 and its protein", "hsp90 and its protein kinase", "and its protein kinase clients.", "its protein kinase clients. cdc37", "protein kinase clients. cdc37 is", "kinase clients. cdc37 is frequently", "clients. cdc37 is frequently over", "cdc37 is frequently over expressed", "is frequently over expressed in", "frequently over expressed in cancers", "over expressed in cancers involving", "expressed in cancers involving mutant", "in cancers involving mutant kinases", "cancers involving mutant kinases and", "involving mutant kinases and acts", "mutant kinases and acts as", "kinases and acts as an", "and acts as an oncogene", "as an oncogene roe", "an oncogene roe et", "oncogene roe et al.", "et al. 2004 reviewed", "al. 2004 reviewed by", "2004 reviewed by gray", "reviewed by gray jr. et", "by gray jr. et al.", "gray jr. et al. 2008", "jr. et al. 2008 .", "et al. 2008 .
              expression", "al. 2008 .
              expression of", "2008 .
              expression of egfrviii", ".
              expression of egfrviii mutant", "
              expression of egfrviii mutant results", "of egfrviii mutant results in", "egfrviii mutant results in aberrant", "mutant results in aberrant activation", "results in aberrant activation of", "in aberrant activation of downstream", "aberrant activation of downstream signaling", "activation of downstream signaling cascades", "downstream signaling cascades namely", "signaling cascades namely ras/raf/map", "cascades namely ras/raf/map kinase", "namely ras/raf/map kinase signaling and", "ras/raf/map kinase signaling and pi3k/akt", "kinase signaling and pi3k/akt signaling", "and pi3k/akt signaling and", "pi3k/akt signaling and possibly", "signaling and possibly signaling", "and possibly signaling by plcg1", "signaling by plcg1 which", "by plcg1 which leads", "plcg1 which leads to", "which leads to increased cell", "leads to increased cell proliferation", "to increased cell proliferation and", "increased cell proliferation and survival", "proliferation and survival providing", "and survival providing selective", "survival providing selective advantage", "providing selective advantage to cancer", "selective advantage to cancer cells", "advantage to cancer cells that", "to cancer cells that harbor", "cancer cells that harbor egfrviii", "that harbor egfrviii huang", "harbor egfrviii huang et", "egfrviii huang et al.", "huang et al. 2007 .", "et al. 2007 .
              ", "al. 2007 .
              egfrviii", "2007 .
              egfrviii mutant", ".
              egfrviii mutant does", "
              egfrviii mutant does not", "egfrviii mutant does not autophosorylate", "mutant does not autophosorylate on", "does not autophosorylate on the", "not autophosorylate on the tyrosine", "autophosorylate on the tyrosine residue", "on the tyrosine residue y1069", "tyrosine residue y1069 i.e.", "residue y1069 i.e. y1045", "y1069 i.e. y1045 in", "i.e. y1045 in the mature", "y1045 in the mature protein", "mature protein a", "protein a docking", "a docking site for cbl", "site for cbl and", "for cbl and is", "cbl and is therefore", "and is therefore unable to", "is therefore unable to recruit", "therefore unable to recruit cbl", "unable to recruit cbl ubiquitin", "to recruit cbl ubiquitin ligase", "cbl ubiquitin ligase which", "ubiquitin ligase which enables", "ligase which enables it", "which enables it to escape", "enables it to escape degradation", "to escape degradation han", "escape degradation han et", "degradation han et al." ] }, { "record_id": "GLY_000594_1_1034", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5649702", "r hsa", "hsa 5649702", "r hsa 5649702" ] }, { "record_id": "GLY_000594_1_1034", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "apex1 independent", "independent resolution", "resolution of", "of ap", "ap sites", "sites via", "via the", "the single", "single nucleotide", "nucleotide replacement", "replacement pathway", "apex1 independent resolution", "independent resolution of", "resolution of ap", "of ap sites", "ap sites via", "sites via the", "via the single", "the single nucleotide", "single nucleotide replacement", "nucleotide replacement pathway", "apex1 independent resolution of", "independent resolution of ap", "resolution of ap sites", "of ap sites via", "ap sites via the", "sites via the single", "via the single nucleotide", "the single nucleotide replacement", "single nucleotide replacement pathway", "apex1 independent resolution of ap", "independent resolution of ap sites", "resolution of ap sites via", "of ap sites via the", "ap sites via the single", "sites via the single nucleotide", "via the single nucleotide replacement", "the single nucleotide replacement pathway", "neil1 and", "and neil2", "neil2 have", "have a", "a dual", "dual dna", "dna glycosylase", "glycosylase and", "and beta/delta", "beta/delta lyase", "lyase activity.", "activity. the", "the ap", "site directed", "directed lyase", "lyase activity", "activity of", "of neil1", "neil2 is", "is their", "their major", "major physiological", "physiological role", "as they", "they can", "can act", "act on", "on ap", "sites generated", "generated spontaneously", "spontaneously or", "or by", "by other", "other dna", "dna glycosylases.", "glycosylases. neil1", "neil1 or", "or neil2", "neil2 cleave", "cleave the", "the damaged", "damaged dna", "dna strand", "strand 5'", "5' to", "to the", "ap site", "producing a", "a 3'", "3' phosphate", "phosphate terminus", "and a", "a 5'", "5' deoxyribose", "deoxyribose phosphate", "5'drp .", ". dna", "dna polymerase", "polymerase beta", "excises 5'drp", "5'drp residue", "residue but", "but is", "is unable", "unable to", "to add", "add the", "the replacement", "replacement nucleotide", "nucleotide to", "to dna", "dna with", "with the", "the 3'pi", "3'pi end.", "end. pnkp", "a dna", "dna 3'", "3' phosphatase", "removes 3'pi", "3'pi and", "and enables", "enables polb", "polb to", "to incorporate", "incorporate the", "which is", "is followed", "followed by", "by ligation", "ligation of", "of repaired", "repaired dna", "strand by", "by xrcc1:lig3", "xrcc1:lig3 complex", "whitehouse et", "et al.", "al. 2001", "wiederhold et", "al. 2004", "das et", "al. 2006", "2006 .", "neil1 and neil2", "and neil2 have", "neil2 have a", "have a dual", "a dual dna", "dual dna glycosylase", "dna glycosylase and", "glycosylase and beta/delta", "and beta/delta lyase", "beta/delta lyase activity.", "lyase activity. the", "activity. the ap", "ap apurinic/apyrimidinic", "apurinic/apyrimidinic site", "site directed lyase", "directed lyase activity", "lyase activity of", "activity of neil1", "of neil1 and", "and neil2 is", "neil2 is their", "is their major", "their major physiological", "major physiological role", "role as", "as they can", "they can act", "can act on", "act on ap", "on ap sites", "ap sites generated", "sites generated spontaneously", "generated spontaneously or", "spontaneously or by", "or by other", "by other dna", "other dna glycosylases.", "dna glycosylases. neil1", "glycosylases. neil1 or", "neil1 or neil2", "or neil2 cleave", "neil2 cleave the", "cleave the damaged", "the damaged dna", "damaged dna strand", "dna strand 5'", "strand 5' to", "5' to the", "to the ap", "the ap site", "site producing", "producing a 3'", "a 3' phosphate", "3' phosphate terminus", "terminus 3'pi", "and a 5'", "a 5' deoxyribose", "5' deoxyribose phosphate", "deoxyribose phosphate terminus", "terminus 5'drp", "5'drp . dna", ". dna polymerase", "dna polymerase beta", "beta polb", "polb excises", "excises 5'drp residue", "5'drp residue but", "residue but is", "but is unable", "is unable to", "unable to add", "to add the", "add the replacement", "the replacement nucleotide", "replacement nucleotide to", "nucleotide to dna", "to dna with", "dna with the", "with the 3'pi", "the 3'pi end.", "3'pi end. pnkp", "pnkp a", "a dna 3'", "dna 3' phosphatase", "phosphatase removes", "removes 3'pi and", "3'pi and enables", "and enables polb", "enables polb to", "polb to incorporate", "to incorporate the", "incorporate the replacement", "nucleotide which", "which is followed", "is followed by", "followed by ligation", "by ligation of", "ligation of repaired", "of repaired dna", "repaired dna strand", "dna strand by", "strand by xrcc1:lig3", "by xrcc1:lig3 complex", "complex whitehouse", "whitehouse et al.", "et al. 2001", "2001 wiederhold", "wiederhold et al.", "et al. 2004", "2004 das", "das et al.", "et al. 2006", "al. 2006 .", "neil1 and neil2 have", "and neil2 have a", "neil2 have a dual", "have a dual dna", "a dual dna glycosylase", "dual dna glycosylase and", "dna glycosylase and beta/delta", "glycosylase and beta/delta lyase", "and beta/delta lyase activity.", "beta/delta lyase activity. the", "lyase activity. the ap", "the ap apurinic/apyrimidinic", "apurinic/apyrimidinic site directed", "site directed lyase activity", "directed lyase activity of", "lyase activity of neil1", "activity of neil1 and", "of neil1 and neil2", "neil1 and neil2 is", "and neil2 is their", "neil2 is their major", "is their major physiological", "their major physiological role", "physiological role as", "role as they", "as they can act", "they can act on", "can act on ap", "act on ap sites", "on ap sites generated", "ap sites generated spontaneously", "sites generated spontaneously or", "generated spontaneously or by", "spontaneously or by other", "or by other dna", "by other dna glycosylases.", "other dna glycosylases. neil1", "dna glycosylases. neil1 or", "glycosylases. neil1 or neil2", "neil1 or neil2 cleave", "or neil2 cleave the", "neil2 cleave the damaged", "cleave the damaged dna", "the damaged dna strand", "damaged dna strand 5'", "dna strand 5' to", "strand 5' to the", "5' to the ap", "to the ap site", "ap site producing", "site producing a", "producing a 3' phosphate", "a 3' phosphate terminus", "phosphate terminus 3'pi", "3'pi and a", "and a 5' deoxyribose", "a 5' deoxyribose phosphate", "5' deoxyribose phosphate terminus", "phosphate terminus 5'drp", "terminus 5'drp .", "5'drp . dna polymerase", ". dna polymerase beta", "polymerase beta polb", "polb excises 5'drp", "excises 5'drp residue but", "5'drp residue but is", "residue but is unable", "but is unable to", "is unable to add", "unable to add the", "to add the replacement", "add the replacement nucleotide", "the replacement nucleotide to", "replacement nucleotide to dna", "nucleotide to dna with", "to dna with the", "dna with the 3'pi", "with the 3'pi end.", "the 3'pi end. pnkp", "end. pnkp a", "pnkp a dna", "a dna 3' phosphatase", "3' phosphatase removes", "phosphatase removes 3'pi", "removes 3'pi and enables", "3'pi and enables polb", "and enables polb to", "enables polb to incorporate", "polb to incorporate the", "to incorporate the replacement", "incorporate the replacement nucleotide", "replacement nucleotide which", "nucleotide which is", "which is followed by", "is followed by ligation", "followed by ligation of", "by ligation of repaired", "ligation of repaired dna", "of repaired dna strand", "repaired dna strand by", "dna strand by xrcc1:lig3", "strand by xrcc1:lig3 complex", "xrcc1:lig3 complex whitehouse", "complex whitehouse et", "whitehouse et al. 2001", "al. 2001 wiederhold", "2001 wiederhold et", "wiederhold et al. 2004", "al. 2004 das", "2004 das et", "das et al. 2006", "et al. 2006 .", "neil1 and neil2 have a", "and neil2 have a dual", "neil2 have a dual dna", "have a dual dna glycosylase", "a dual dna glycosylase and", "dual dna glycosylase and beta/delta", "dna glycosylase and beta/delta lyase", "glycosylase and beta/delta lyase activity.", "and beta/delta lyase activity. the", "beta/delta lyase activity. the ap", "activity. the ap apurinic/apyrimidinic", "ap apurinic/apyrimidinic site", "apurinic/apyrimidinic site directed lyase", "site directed lyase activity of", "directed lyase activity of neil1", "lyase activity of neil1 and", "activity of neil1 and neil2", "of neil1 and neil2 is", "neil1 and neil2 is their", "and neil2 is their major", "neil2 is their major physiological", "is their major physiological role", "major physiological role as", "physiological role as they", "role as they can", "as they can act on", "they can act on ap", "can act on ap sites", "act on ap sites generated", "on ap sites generated spontaneously", "ap sites generated spontaneously or", "sites generated spontaneously or by", "generated spontaneously or by other", "spontaneously or by other dna", "or by other dna glycosylases.", "by other dna glycosylases. neil1", "other dna glycosylases. neil1 or", "dna glycosylases. neil1 or neil2", "glycosylases. neil1 or neil2 cleave", "neil1 or neil2 cleave the", "or neil2 cleave the damaged", "neil2 cleave the damaged dna", "cleave the damaged dna strand", "the damaged dna strand 5'", "damaged dna strand 5' to", "dna strand 5' to the", "strand 5' to the ap", "5' to the ap site", "the ap site producing", "ap site producing a", "site producing a 3'", "producing a 3' phosphate terminus", "3' phosphate terminus 3'pi", "terminus 3'pi and", "3'pi and a 5'", "and a 5' deoxyribose phosphate", "a 5' deoxyribose phosphate terminus", "deoxyribose phosphate terminus 5'drp", "phosphate terminus 5'drp .", "terminus 5'drp . dna", "5'drp . dna polymerase beta", "dna polymerase beta polb", "beta polb excises", "polb excises 5'drp residue", "excises 5'drp residue but is", "5'drp residue but is unable", "residue but is unable to", "but is unable to add", "is unable to add the", "unable to add the replacement", "to add the replacement nucleotide", "add the replacement nucleotide to", "the replacement nucleotide to dna", "replacement nucleotide to dna with", "nucleotide to dna with the", "to dna with the 3'pi", "dna with the 3'pi end.", "with the 3'pi end. pnkp", "3'pi end. pnkp a", "end. pnkp a dna", "pnkp a dna 3'", "dna 3' phosphatase removes", "3' phosphatase removes 3'pi", "phosphatase removes 3'pi and", "removes 3'pi and enables polb", "3'pi and enables polb to", "and enables polb to incorporate", "enables polb to incorporate the", "polb to incorporate the replacement", "to incorporate the replacement nucleotide", "the replacement nucleotide which", "replacement nucleotide which is", "nucleotide which is followed", "which is followed by ligation", "is followed by ligation of", "followed by ligation of repaired", "by ligation of repaired dna", "ligation of repaired dna strand", "of repaired dna strand by", "repaired dna strand by xrcc1:lig3", "dna strand by xrcc1:lig3 complex", "by xrcc1:lig3 complex whitehouse", "xrcc1:lig3 complex whitehouse et", "complex whitehouse et al.", "et al. 2001 wiederhold", "al. 2001 wiederhold et", "2001 wiederhold et al.", "et al. 2004 das", "al. 2004 das et", "2004 das et al.", "das et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1035", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5653890", "r hsa", "hsa 5653890", "r hsa 5653890" ] }, { "record_id": "GLY_000594_1_1035", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lactose synthesis", "synthesis of", "of the", "the disaccharide", "disaccharide lactose", "lactose takes", "takes place", "place within", "within the", "the golgi", "golgi apparatus", "apparatus of", "of epithelial", "epithelial cells", "cells of", "the lactating", "lactating mammary", "mammary gland.", "gland. the", "the synthesis", "synthesis itself", "itself is", "is a", "a single", "single chemical", "chemical reaction", "reaction of", "of free", "free glucose", "glucose and", "and udp", "udp galactose", "galactose to", "to form", "form lactose", "lactose and", "and udp.", "udp. for", "for this", "this reaction", "reaction to", "to occur", "glucose is", "is transported", "transported from", "from the", "the cytosol", "cytosol into", "into the", "golgi lumen", "and b4galt1", "b4galt1 interacts", "interacts with", "with lalba", "alpha lactalbumin", "to modulate", "modulate its", "its substrate", "substrate specificity", "brew and", "and hill", "hill 1975", "1975 .", "synthesis of the", "of the disaccharide", "the disaccharide lactose", "disaccharide lactose takes", "lactose takes place", "takes place within", "place within the", "within the golgi", "the golgi apparatus", "golgi apparatus of", "apparatus of epithelial", "of epithelial cells", "epithelial cells of", "cells of the", "of the lactating", "the lactating mammary", "lactating mammary gland.", "mammary gland. the", "gland. the synthesis", "the synthesis itself", "synthesis itself is", "itself is a", "is a single", "a single chemical", "single chemical reaction", "chemical reaction of", "reaction of free", "of free glucose", "free glucose and", "glucose and udp", "and udp galactose", "udp galactose to", "galactose to form", "to form lactose", "form lactose and", "lactose and udp.", "and udp. for", "udp. for this", "for this reaction", "this reaction to", "reaction to occur", "occur glucose", "glucose is transported", "is transported from", "transported from the", "from the cytosol", "the cytosol into", "cytosol into the", "into the golgi", "the golgi lumen", "lumen and", "and b4galt1 interacts", "b4galt1 interacts with", "interacts with lalba", "lalba alpha", "lactalbumin to", "to modulate its", "modulate its substrate", "its substrate specificity", "specificity brew", "brew and hill", "and hill 1975", "hill 1975 .", "synthesis of the disaccharide", "of the disaccharide lactose", "the disaccharide lactose takes", "disaccharide lactose takes place", "lactose takes place within", "takes place within the", "place within the golgi", "within the golgi apparatus", "the golgi apparatus of", "golgi apparatus of epithelial", "apparatus of epithelial cells", "of epithelial cells of", "epithelial cells of the", "cells of the lactating", "of the lactating mammary", "the lactating mammary gland.", "lactating mammary gland. the", "mammary gland. the synthesis", "gland. the synthesis itself", "the synthesis itself is", "synthesis itself is a", "itself is a single", "is a single chemical", "a single chemical reaction", "single chemical reaction of", "chemical reaction of free", "reaction of free glucose", "of free glucose and", "free glucose and udp", "glucose and udp galactose", "and udp galactose to", "udp galactose to form", "galactose to form lactose", "to form lactose and", "form lactose and udp.", "lactose and udp. for", "and udp. for this", "udp. for this reaction", "for this reaction to", "this reaction to occur", "to occur glucose", "occur glucose is", "glucose is transported from", "is transported from the", "transported from the cytosol", "from the cytosol into", "the cytosol into the", "cytosol into the golgi", "into the golgi lumen", "golgi lumen and", "lumen and b4galt1", "and b4galt1 interacts with", "b4galt1 interacts with lalba", "with lalba alpha", "lalba alpha lactalbumin", "alpha lactalbumin to", "lactalbumin to modulate", "to modulate its substrate", "modulate its substrate specificity", "substrate specificity brew", "specificity brew and", "brew and hill 1975", "and hill 1975 .", "synthesis of the disaccharide lactose", "of the disaccharide lactose takes", "the disaccharide lactose takes place", "disaccharide lactose takes place within", "lactose takes place within the", "takes place within the golgi", "place within the golgi apparatus", "within the golgi apparatus of", "the golgi apparatus of epithelial", "golgi apparatus of epithelial cells", "apparatus of epithelial cells of", "of epithelial cells of the", "epithelial cells of the lactating", "cells of the lactating mammary", "of the lactating mammary gland.", "the lactating mammary gland. the", "lactating mammary gland. the synthesis", "mammary gland. the synthesis itself", "gland. the synthesis itself is", "the synthesis itself is a", "synthesis itself is a single", "itself is a single chemical", "is a single chemical reaction", "a single chemical reaction of", "single chemical reaction of free", "chemical reaction of free glucose", "reaction of free glucose and", "of free glucose and udp", "free glucose and udp galactose", "glucose and udp galactose to", "and udp galactose to form", "udp galactose to form lactose", "galactose to form lactose and", "to form lactose and udp.", "form lactose and udp. for", "lactose and udp. for this", "and udp. for this reaction", "udp. for this reaction to", "for this reaction to occur", "reaction to occur glucose", "to occur glucose is", "occur glucose is transported", "glucose is transported from the", "is transported from the cytosol", "transported from the cytosol into", "from the cytosol into the", "the cytosol into the golgi", "cytosol into the golgi lumen", "the golgi lumen and", "golgi lumen and b4galt1", "lumen and b4galt1 interacts", "and b4galt1 interacts with lalba", "interacts with lalba alpha", "with lalba alpha lactalbumin", "alpha lactalbumin to modulate", "lactalbumin to modulate its", "to modulate its substrate specificity", "its substrate specificity brew", "substrate specificity brew and", "specificity brew and hill", "brew and hill 1975 ." ] }, { "record_id": "GLY_000594_1_1036", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654219", "r hsa", "hsa 5654219", "r hsa 5654219" ] }, { "record_id": "GLY_000594_1_1036", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phospholipase c", "c mediated", "mediated cascade:", "cascade: fgfr1", "phospholipase c mediated", "c mediated cascade:", "mediated cascade: fgfr1", "phospholipase c mediated cascade:", "c mediated cascade: fgfr1", "phospholipase c mediated cascade: fgfr1", "c gamma", "plc gamma", "is a", "a substrate", "substrate of", "of the", "the fibroblast", "fibroblast growth", "growth factor", "factor receptor", "and other", "other receptors", "receptors with", "with tyrosine", "tyrosine kinase", "kinase activity.", "activity. it", "it is", "is known", "known that", "that the", "the src", "src homology", "homology region", "region 2", "sh2 domain", "of plc", "gamma and", "and of", "of other", "other signaling", "signaling molecules", "such as", "as gtpase", "gtpase activating", "activating protein", "protein and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 kinase", "kinase associated", "associated p85", "direct their", "their binding", "binding toward", "toward autophosphorylated", "autophosphorylated tyrosine", "tyrosine residues", "residues of", "the fgfr.", "fgfr. recruitment", "recruitment of", "gamma results", "results in", "in its", "its phosphorylation", "phosphorylation and", "and activation", "activation by", "by the", "the receptor.", "activated plc", "gamma hydrolyzes", "hydrolyzes phosphatidyl", "phosphatidyl inositol", "inositol 4", "4 5", "p2 to", "to form", "form the", "the second", "second messengers", "messengers diacylglycerol", "and ins", "1 4", "5 p3", "which stimulate", "stimulate calcium", "calcium release", "release and", "activation of", "of calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinases.
              ", "phospholipase c gamma", "gamma plc", "gamma is", "is a substrate", "a substrate of", "substrate of the", "of the fibroblast", "the fibroblast growth", "fibroblast growth factor", "growth factor receptor", "receptor fgfr", "fgfr and", "and other receptors", "other receptors with", "receptors with tyrosine", "with tyrosine kinase", "tyrosine kinase activity.", "kinase activity. it", "activity. it is", "it is known", "is known that", "known that the", "that the src", "the src homology", "src homology region", "homology region 2", "2 sh2", "domain of", "of plc gamma", "plc gamma and", "gamma and of", "and of other", "of other signaling", "other signaling molecules", "molecules such", "such as gtpase", "as gtpase activating", "gtpase activating protein", "activating protein and", "protein and phosphatidylinositol", "and phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "3 kinase associated", "kinase associated p85", "p85 direct", "direct their binding", "their binding toward", "binding toward autophosphorylated", "toward autophosphorylated tyrosine", "autophosphorylated tyrosine residues", "tyrosine residues of", "residues of the", "of the fgfr.", "the fgfr. recruitment", "fgfr. recruitment of", "recruitment of plc", "plc gamma results", "gamma results in", "results in its", "in its phosphorylation", "its phosphorylation and", "phosphorylation and activation", "and activation by", "activation by the", "by the receptor.", "receptor. activated", "activated plc gamma", "plc gamma hydrolyzes", "gamma hydrolyzes phosphatidyl", "hydrolyzes phosphatidyl inositol", "phosphatidyl inositol 4", "inositol 4 5", "5 p2", "p2 to form", "to form the", "form the second", "the second messengers", "second messengers diacylglycerol", "diacylglycerol dag", "dag and", "ins 1", "1 4 5", "4 5 p3", "p3 which", "which stimulate calcium", "stimulate calcium release", "calcium release and", "release and activation", "and activation of", "activation of calcium/calmodulin", "of calcium/calmodulin dependent", "calcium/calmodulin dependent kinases.
              ", "c gamma plc", "gamma plc gamma", "plc gamma is", "gamma is a", "is a substrate of", "a substrate of the", "substrate of the fibroblast", "of the fibroblast growth", "the fibroblast growth factor", "fibroblast growth factor receptor", "factor receptor fgfr", "fgfr and other", "and other receptors with", "other receptors with tyrosine", "receptors with tyrosine kinase", "with tyrosine kinase activity.", "tyrosine kinase activity. it", "kinase activity. it is", "activity. it is known", "it is known that", "is known that the", "known that the src", "that the src homology", "the src homology region", "src homology region 2", "region 2 sh2", "2 sh2 domain", "sh2 domain of", "domain of plc", "of plc gamma and", "plc gamma and of", "gamma and of other", "and of other signaling", "of other signaling molecules", "signaling molecules such", "molecules such as", "such as gtpase activating", "as gtpase activating protein", "gtpase activating protein and", "activating protein and phosphatidylinositol", "protein and phosphatidylinositol 3", "and phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase associated", "3 kinase associated p85", "associated p85 direct", "p85 direct their", "direct their binding toward", "their binding toward autophosphorylated", "binding toward autophosphorylated tyrosine", "toward autophosphorylated tyrosine residues", "autophosphorylated tyrosine residues of", "tyrosine residues of the", "residues of the fgfr.", "of the fgfr. recruitment", "the fgfr. recruitment of", "fgfr. recruitment of plc", "recruitment of plc gamma", "of plc gamma results", "plc gamma results in", "gamma results in its", "results in its phosphorylation", "in its phosphorylation and", "its phosphorylation and activation", "phosphorylation and activation by", "and activation by the", "activation by the receptor.", "the receptor. activated", "receptor. activated plc", "activated plc gamma hydrolyzes", "plc gamma hydrolyzes phosphatidyl", "gamma hydrolyzes phosphatidyl inositol", "hydrolyzes phosphatidyl inositol 4", "phosphatidyl inositol 4 5", "4 5 p2", "5 p2 to", "p2 to form the", "to form the second", "form the second messengers", "the second messengers diacylglycerol", "messengers diacylglycerol dag", "dag and ins", "and ins 1", "ins 1 4", "1 4 5 p3", "5 p3 which", "p3 which stimulate", "which stimulate calcium release", "stimulate calcium release and", "calcium release and activation", "release and activation of", "and activation of calcium/calmodulin", "activation of calcium/calmodulin dependent", "of calcium/calmodulin dependent kinases.
              ", "phospholipase c gamma plc", "c gamma plc gamma", "plc gamma is a", "gamma is a substrate", "is a substrate of the", "a substrate of the fibroblast", "substrate of the fibroblast growth", "of the fibroblast growth factor", "the fibroblast growth factor receptor", "growth factor receptor fgfr", "receptor fgfr and", "fgfr and other receptors", "and other receptors with tyrosine", "other receptors with tyrosine kinase", "receptors with tyrosine kinase activity.", "with tyrosine kinase activity. it", "tyrosine kinase activity. it is", "kinase activity. it is known", "activity. it is known that", "it is known that the", "is known that the src", "known that the src homology", "that the src homology region", "the src homology region 2", "homology region 2 sh2", "region 2 sh2 domain", "sh2 domain of plc", "domain of plc gamma", "of plc gamma and of", "plc gamma and of other", "gamma and of other signaling", "and of other signaling molecules", "other signaling molecules such", "signaling molecules such as", "molecules such as gtpase", "such as gtpase activating protein", "as gtpase activating protein and", "gtpase activating protein and phosphatidylinositol", "activating protein and phosphatidylinositol 3", "protein and phosphatidylinositol 3 kinase", "and phosphatidylinositol 3 kinase associated", "phosphatidylinositol 3 kinase associated p85", "kinase associated p85 direct", "associated p85 direct their", "p85 direct their binding", "direct their binding toward autophosphorylated", "their binding toward autophosphorylated tyrosine", "binding toward autophosphorylated tyrosine residues", "toward autophosphorylated tyrosine residues of", "autophosphorylated tyrosine residues of the", "tyrosine residues of the fgfr.", "residues of the fgfr. recruitment", "of the fgfr. recruitment of", "the fgfr. recruitment of plc", "fgfr. recruitment of plc gamma", "recruitment of plc gamma results", "of plc gamma results in", "plc gamma results in its", "gamma results in its phosphorylation", "results in its phosphorylation and", "in its phosphorylation and activation", "its phosphorylation and activation by", "phosphorylation and activation by the", "and activation by the receptor.", "by the receptor. activated", "the receptor. activated plc", "receptor. activated plc gamma", "activated plc gamma hydrolyzes phosphatidyl", "plc gamma hydrolyzes phosphatidyl inositol", "gamma hydrolyzes phosphatidyl inositol 4", "hydrolyzes phosphatidyl inositol 4 5", "inositol 4 5 p2", "4 5 p2 to", "5 p2 to form", "p2 to form the second", "to form the second messengers", "form the second messengers diacylglycerol", "second messengers diacylglycerol dag", "diacylglycerol dag and", "and ins 1 4", "ins 1 4 5", "4 5 p3 which", "5 p3 which stimulate", "p3 which stimulate calcium", "which stimulate calcium release and", "stimulate calcium release and activation", "calcium release and activation of", "release and activation of calcium/calmodulin", "and activation of calcium/calmodulin dependent", "activation of calcium/calmodulin dependent kinases.
              " ] }, { "record_id": "GLY_000594_1_1037", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654221", "r hsa", "hsa 5654221", "r hsa 5654221" ] }, { "record_id": "GLY_000594_1_1037", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phospholipase c", "c mediated", "mediated cascade", "phospholipase c mediated", "c mediated cascade", "cascade fgfr2", "phospholipase c mediated cascade", "mediated cascade fgfr2", "c mediated cascade fgfr2", "c gamma", "plc gamma", "is a", "a substrate", "substrate of", "of the", "the fibroblast", "fibroblast growth", "growth factor", "factor receptor", "and other", "other receptors", "receptors with", "with tyrosine", "tyrosine kinase", "kinase activity.", "activity. it", "it is", "is known", "known that", "that the", "the src", "src homology", "homology region", "region 2", "sh2 domain", "of plc", "gamma and", "and of", "of other", "other signaling", "signaling molecules", "such as", "as gtpase", "gtpase activating", "activating protein", "protein and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 kinase", "kinase associated", "associated p85", "direct their", "their binding", "binding toward", "toward autophosphorylated", "autophosphorylated tyrosine", "tyrosine residues", "residues of", "the fgfr.", "fgfr. recruitment", "recruitment of", "gamma results", "results in", "in its", "its phosphorylation", "phosphorylation and", "and activation", "activation by", "by the", "the receptor.", "activated plc", "gamma hydrolyzes", "hydrolyzes phosphatidyl", "phosphatidyl inositol", "inositol 4", "4 5", "p2 to", "to form", "form the", "the second", "second messengers", "messengers diacylglycerol", "and ins", "1 4", "5 p3", "which stimulate", "stimulate calcium", "calcium release", "release and", "activation of", "of calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinases.
              ", "phospholipase c gamma", "gamma plc", "gamma is", "is a substrate", "a substrate of", "substrate of the", "of the fibroblast", "the fibroblast growth", "fibroblast growth factor", "growth factor receptor", "receptor fgfr", "fgfr and", "and other receptors", "other receptors with", "receptors with tyrosine", "with tyrosine kinase", "tyrosine kinase activity.", "kinase activity. it", "activity. it is", "it is known", "is known that", "known that the", "that the src", "the src homology", "src homology region", "homology region 2", "2 sh2", "domain of", "of plc gamma", "plc gamma and", "gamma and of", "and of other", "of other signaling", "other signaling molecules", "molecules such", "such as gtpase", "as gtpase activating", "gtpase activating protein", "activating protein and", "protein and phosphatidylinositol", "and phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "3 kinase associated", "kinase associated p85", "p85 direct", "direct their binding", "their binding toward", "binding toward autophosphorylated", "toward autophosphorylated tyrosine", "autophosphorylated tyrosine residues", "tyrosine residues of", "residues of the", "of the fgfr.", "the fgfr. recruitment", "fgfr. recruitment of", "recruitment of plc", "plc gamma results", "gamma results in", "results in its", "in its phosphorylation", "its phosphorylation and", "phosphorylation and activation", "and activation by", "activation by the", "by the receptor.", "receptor. activated", "activated plc gamma", "plc gamma hydrolyzes", "gamma hydrolyzes phosphatidyl", "hydrolyzes phosphatidyl inositol", "phosphatidyl inositol 4", "inositol 4 5", "5 p2", "p2 to form", "to form the", "form the second", "the second messengers", "second messengers diacylglycerol", "diacylglycerol dag", "dag and", "ins 1", "1 4 5", "4 5 p3", "p3 which", "which stimulate calcium", "stimulate calcium release", "calcium release and", "release and activation", "and activation of", "activation of calcium/calmodulin", "of calcium/calmodulin dependent", "calcium/calmodulin dependent kinases.
              ", "c gamma plc", "gamma plc gamma", "plc gamma is", "gamma is a", "is a substrate of", "a substrate of the", "substrate of the fibroblast", "of the fibroblast growth", "the fibroblast growth factor", "fibroblast growth factor receptor", "factor receptor fgfr", "fgfr and other", "and other receptors with", "other receptors with tyrosine", "receptors with tyrosine kinase", "with tyrosine kinase activity.", "tyrosine kinase activity. it", "kinase activity. it is", "activity. it is known", "it is known that", "is known that the", "known that the src", "that the src homology", "the src homology region", "src homology region 2", "region 2 sh2", "2 sh2 domain", "sh2 domain of", "domain of plc", "of plc gamma and", "plc gamma and of", "gamma and of other", "and of other signaling", "of other signaling molecules", "signaling molecules such", "molecules such as", "such as gtpase activating", "as gtpase activating protein", "gtpase activating protein and", "activating protein and phosphatidylinositol", "protein and phosphatidylinositol 3", "and phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase associated", "3 kinase associated p85", "associated p85 direct", "p85 direct their", "direct their binding toward", "their binding toward autophosphorylated", "binding toward autophosphorylated tyrosine", "toward autophosphorylated tyrosine residues", "autophosphorylated tyrosine residues of", "tyrosine residues of the", "residues of the fgfr.", "of the fgfr. recruitment", "the fgfr. recruitment of", "fgfr. recruitment of plc", "recruitment of plc gamma", "of plc gamma results", "plc gamma results in", "gamma results in its", "results in its phosphorylation", "in its phosphorylation and", "its phosphorylation and activation", "phosphorylation and activation by", "and activation by the", "activation by the receptor.", "the receptor. activated", "receptor. activated plc", "activated plc gamma hydrolyzes", "plc gamma hydrolyzes phosphatidyl", "gamma hydrolyzes phosphatidyl inositol", "hydrolyzes phosphatidyl inositol 4", "phosphatidyl inositol 4 5", "4 5 p2", "5 p2 to", "p2 to form the", "to form the second", "form the second messengers", "the second messengers diacylglycerol", "messengers diacylglycerol dag", "dag and ins", "and ins 1", "ins 1 4", "1 4 5 p3", "5 p3 which", "p3 which stimulate", "which stimulate calcium release", "stimulate calcium release and", "calcium release and activation", "release and activation of", "and activation of calcium/calmodulin", "activation of calcium/calmodulin dependent", "of calcium/calmodulin dependent kinases.
              ", "phospholipase c gamma plc", "c gamma plc gamma", "plc gamma is a", "gamma is a substrate", "is a substrate of the", "a substrate of the fibroblast", "substrate of the fibroblast growth", "of the fibroblast growth factor", "the fibroblast growth factor receptor", "growth factor receptor fgfr", "receptor fgfr and", "fgfr and other receptors", "and other receptors with tyrosine", "other receptors with tyrosine kinase", "receptors with tyrosine kinase activity.", "with tyrosine kinase activity. it", "tyrosine kinase activity. it is", "kinase activity. it is known", "activity. it is known that", "it is known that the", "is known that the src", "known that the src homology", "that the src homology region", "the src homology region 2", "homology region 2 sh2", "region 2 sh2 domain", "sh2 domain of plc", "domain of plc gamma", "of plc gamma and of", "plc gamma and of other", "gamma and of other signaling", "and of other signaling molecules", "other signaling molecules such", "signaling molecules such as", "molecules such as gtpase", "such as gtpase activating protein", "as gtpase activating protein and", "gtpase activating protein and phosphatidylinositol", "activating protein and phosphatidylinositol 3", "protein and phosphatidylinositol 3 kinase", "and phosphatidylinositol 3 kinase associated", "phosphatidylinositol 3 kinase associated p85", "kinase associated p85 direct", "associated p85 direct their", "p85 direct their binding", "direct their binding toward autophosphorylated", "their binding toward autophosphorylated tyrosine", "binding toward autophosphorylated tyrosine residues", "toward autophosphorylated tyrosine residues of", "autophosphorylated tyrosine residues of the", "tyrosine residues of the fgfr.", "residues of the fgfr. recruitment", "of the fgfr. recruitment of", "the fgfr. recruitment of plc", "fgfr. recruitment of plc gamma", "recruitment of plc gamma results", "of plc gamma results in", "plc gamma results in its", "gamma results in its phosphorylation", "results in its phosphorylation and", "in its phosphorylation and activation", "its phosphorylation and activation by", "phosphorylation and activation by the", "and activation by the receptor.", "by the receptor. activated", "the receptor. activated plc", "receptor. activated plc gamma", "activated plc gamma hydrolyzes phosphatidyl", "plc gamma hydrolyzes phosphatidyl inositol", "gamma hydrolyzes phosphatidyl inositol 4", "hydrolyzes phosphatidyl inositol 4 5", "inositol 4 5 p2", "4 5 p2 to", "5 p2 to form", "p2 to form the second", "to form the second messengers", "form the second messengers diacylglycerol", "second messengers diacylglycerol dag", "diacylglycerol dag and", "and ins 1 4", "ins 1 4 5", "4 5 p3 which", "5 p3 which stimulate", "p3 which stimulate calcium", "which stimulate calcium release and", "stimulate calcium release and activation", "calcium release and activation of", "release and activation of calcium/calmodulin", "and activation of calcium/calmodulin dependent", "activation of calcium/calmodulin dependent kinases.
              " ] }, { "record_id": "GLY_000594_1_1038", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654227", "r hsa", "hsa 5654227", "r hsa 5654227" ] }, { "record_id": "GLY_000594_1_1038", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phospholipase c", "c mediated", "mediated cascade", "phospholipase c mediated", "c mediated cascade", "cascade fgfr3", "phospholipase c mediated cascade", "mediated cascade fgfr3", "c mediated cascade fgfr3", "c gamma", "plc gamma", "is a", "a substrate", "substrate of", "of the", "the fibroblast", "fibroblast growth", "growth factor", "factor receptor", "and other", "other receptors", "receptors with", "with tyrosine", "tyrosine kinase", "kinase activity.", "activity. it", "it is", "is known", "known that", "that the", "the src", "src homology", "homology region", "region 2", "sh2 domain", "of plc", "gamma and", "and of", "of other", "other signaling", "signaling molecules", "such as", "as gtpase", "gtpase activating", "activating protein", "protein and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 kinase", "kinase associated", "associated p85", "direct their", "their binding", "binding toward", "toward autophosphorylated", "autophosphorylated tyrosine", "tyrosine residues", "residues of", "the fgfr.", "fgfr. recruitment", "recruitment of", "gamma results", "results in", "in its", "its phosphorylation", "phosphorylation and", "and activation", "activation by", "by the", "the receptor.", "activated plc", "gamma hydrolyzes", "hydrolyzes phosphatidyl", "phosphatidyl inositol", "inositol 4", "4 5", "p2 to", "to form", "form the", "the second", "second messengers", "messengers diacylglycerol", "and ins", "1 4", "5 p3", "which stimulate", "stimulate calcium", "calcium release", "release and", "activation of", "of calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinases.
              ", "phospholipase c gamma", "gamma plc", "gamma is", "is a substrate", "a substrate of", "substrate of the", "of the fibroblast", "the fibroblast growth", "fibroblast growth factor", "growth factor receptor", "receptor fgfr", "fgfr and", "and other receptors", "other receptors with", "receptors with tyrosine", "with tyrosine kinase", "tyrosine kinase activity.", "kinase activity. it", "activity. it is", "it is known", "is known that", "known that the", "that the src", "the src homology", "src homology region", "homology region 2", "2 sh2", "domain of", "of plc gamma", "plc gamma and", "gamma and of", "and of other", "of other signaling", "other signaling molecules", "molecules such", "such as gtpase", "as gtpase activating", "gtpase activating protein", "activating protein and", "protein and phosphatidylinositol", "and phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "3 kinase associated", "kinase associated p85", "p85 direct", "direct their binding", "their binding toward", "binding toward autophosphorylated", "toward autophosphorylated tyrosine", "autophosphorylated tyrosine residues", "tyrosine residues of", "residues of the", "of the fgfr.", "the fgfr. recruitment", "fgfr. recruitment of", "recruitment of plc", "plc gamma results", "gamma results in", "results in its", "in its phosphorylation", "its phosphorylation and", "phosphorylation and activation", "and activation by", "activation by the", "by the receptor.", "receptor. activated", "activated plc gamma", "plc gamma hydrolyzes", "gamma hydrolyzes phosphatidyl", "hydrolyzes phosphatidyl inositol", "phosphatidyl inositol 4", "inositol 4 5", "5 p2", "p2 to form", "to form the", "form the second", "the second messengers", "second messengers diacylglycerol", "diacylglycerol dag", "dag and", "ins 1", "1 4 5", "4 5 p3", "p3 which", "which stimulate calcium", "stimulate calcium release", "calcium release and", "release and activation", "and activation of", "activation of calcium/calmodulin", "of calcium/calmodulin dependent", "calcium/calmodulin dependent kinases.
              ", "c gamma plc", "gamma plc gamma", "plc gamma is", "gamma is a", "is a substrate of", "a substrate of the", "substrate of the fibroblast", "of the fibroblast growth", "the fibroblast growth factor", "fibroblast growth factor receptor", "factor receptor fgfr", "fgfr and other", "and other receptors with", "other receptors with tyrosine", "receptors with tyrosine kinase", "with tyrosine kinase activity.", "tyrosine kinase activity. it", "kinase activity. it is", "activity. it is known", "it is known that", "is known that the", "known that the src", "that the src homology", "the src homology region", "src homology region 2", "region 2 sh2", "2 sh2 domain", "sh2 domain of", "domain of plc", "of plc gamma and", "plc gamma and of", "gamma and of other", "and of other signaling", "of other signaling molecules", "signaling molecules such", "molecules such as", "such as gtpase activating", "as gtpase activating protein", "gtpase activating protein and", "activating protein and phosphatidylinositol", "protein and phosphatidylinositol 3", "and phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase associated", "3 kinase associated p85", "associated p85 direct", "p85 direct their", "direct their binding toward", "their binding toward autophosphorylated", "binding toward autophosphorylated tyrosine", "toward autophosphorylated tyrosine residues", "autophosphorylated tyrosine residues of", "tyrosine residues of the", "residues of the fgfr.", "of the fgfr. recruitment", "the fgfr. recruitment of", "fgfr. recruitment of plc", "recruitment of plc gamma", "of plc gamma results", "plc gamma results in", "gamma results in its", "results in its phosphorylation", "in its phosphorylation and", "its phosphorylation and activation", "phosphorylation and activation by", "and activation by the", "activation by the receptor.", "the receptor. activated", "receptor. activated plc", "activated plc gamma hydrolyzes", "plc gamma hydrolyzes phosphatidyl", "gamma hydrolyzes phosphatidyl inositol", "hydrolyzes phosphatidyl inositol 4", "phosphatidyl inositol 4 5", "4 5 p2", "5 p2 to", "p2 to form the", "to form the second", "form the second messengers", "the second messengers diacylglycerol", "messengers diacylglycerol dag", "dag and ins", "and ins 1", "ins 1 4", "1 4 5 p3", "5 p3 which", "p3 which stimulate", "which stimulate calcium release", "stimulate calcium release and", "calcium release and activation", "release and activation of", "and activation of calcium/calmodulin", "activation of calcium/calmodulin dependent", "of calcium/calmodulin dependent kinases.
              ", "phospholipase c gamma plc", "c gamma plc gamma", "plc gamma is a", "gamma is a substrate", "is a substrate of the", "a substrate of the fibroblast", "substrate of the fibroblast growth", "of the fibroblast growth factor", "the fibroblast growth factor receptor", "growth factor receptor fgfr", "receptor fgfr and", "fgfr and other receptors", "and other receptors with tyrosine", "other receptors with tyrosine kinase", "receptors with tyrosine kinase activity.", "with tyrosine kinase activity. it", "tyrosine kinase activity. it is", "kinase activity. it is known", "activity. it is known that", "it is known that the", "is known that the src", "known that the src homology", "that the src homology region", "the src homology region 2", "homology region 2 sh2", "region 2 sh2 domain", "sh2 domain of plc", "domain of plc gamma", "of plc gamma and of", "plc gamma and of other", "gamma and of other signaling", "and of other signaling molecules", "other signaling molecules such", "signaling molecules such as", "molecules such as gtpase", "such as gtpase activating protein", "as gtpase activating protein and", "gtpase activating protein and phosphatidylinositol", "activating protein and phosphatidylinositol 3", "protein and phosphatidylinositol 3 kinase", "and phosphatidylinositol 3 kinase associated", "phosphatidylinositol 3 kinase associated p85", "kinase associated p85 direct", "associated p85 direct their", "p85 direct their binding", "direct their binding toward autophosphorylated", "their binding toward autophosphorylated tyrosine", "binding toward autophosphorylated tyrosine residues", "toward autophosphorylated tyrosine residues of", "autophosphorylated tyrosine residues of the", "tyrosine residues of the fgfr.", "residues of the fgfr. recruitment", "of the fgfr. recruitment of", "the fgfr. recruitment of plc", "fgfr. recruitment of plc gamma", "recruitment of plc gamma results", "of plc gamma results in", "plc gamma results in its", "gamma results in its phosphorylation", "results in its phosphorylation and", "in its phosphorylation and activation", "its phosphorylation and activation by", "phosphorylation and activation by the", "and activation by the receptor.", "by the receptor. activated", "the receptor. activated plc", "receptor. activated plc gamma", "activated plc gamma hydrolyzes phosphatidyl", "plc gamma hydrolyzes phosphatidyl inositol", "gamma hydrolyzes phosphatidyl inositol 4", "hydrolyzes phosphatidyl inositol 4 5", "inositol 4 5 p2", "4 5 p2 to", "5 p2 to form", "p2 to form the second", "to form the second messengers", "form the second messengers diacylglycerol", "second messengers diacylglycerol dag", "diacylglycerol dag and", "and ins 1 4", "ins 1 4 5", "4 5 p3 which", "5 p3 which stimulate", "p3 which stimulate calcium", "which stimulate calcium release and", "stimulate calcium release and activation", "calcium release and activation of", "release and activation of calcium/calmodulin", "and activation of calcium/calmodulin dependent", "activation of calcium/calmodulin dependent kinases.
              " ] }, { "record_id": "GLY_000594_1_1039", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654228", "r hsa", "hsa 5654228", "r hsa 5654228" ] }, { "record_id": "GLY_000594_1_1039", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phospholipase c", "c mediated", "mediated cascade", "phospholipase c mediated", "c mediated cascade", "cascade fgfr4", "phospholipase c mediated cascade", "mediated cascade fgfr4", "c mediated cascade fgfr4", "c gamma", "plc gamma", "is a", "a substrate", "substrate of", "of the", "the fibroblast", "fibroblast growth", "growth factor", "factor receptor", "and other", "other receptors", "receptors with", "with tyrosine", "tyrosine kinase", "kinase activity.", "activity. it", "it is", "is known", "known that", "that the", "the src", "src homology", "homology region", "region 2", "sh2 domain", "of plc", "gamma and", "and of", "of other", "other signaling", "signaling molecules", "such as", "as gtpase", "gtpase activating", "activating protein", "protein and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 kinase", "kinase associated", "associated p85", "direct their", "their binding", "binding toward", "toward autophosphorylated", "autophosphorylated tyrosine", "tyrosine residues", "residues of", "the fgfr.", "fgfr. recruitment", "recruitment of", "gamma results", "results in", "in its", "its phosphorylation", "phosphorylation and", "and activation", "activation by", "by the", "the receptor.", "activated plc", "gamma hydrolyzes", "hydrolyzes phosphatidyl", "phosphatidyl inositol", "inositol 4", "4 5", "p2 to", "to form", "form the", "the second", "second messengers", "messengers diacylglycerol", "and ins", "1 4", "5 p3", "which stimulate", "stimulate calcium", "calcium release", "release and", "activation of", "of calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinases.
              ", "phospholipase c gamma", "gamma plc", "gamma is", "is a substrate", "a substrate of", "substrate of the", "of the fibroblast", "the fibroblast growth", "fibroblast growth factor", "growth factor receptor", "receptor fgfr", "fgfr and", "and other receptors", "other receptors with", "receptors with tyrosine", "with tyrosine kinase", "tyrosine kinase activity.", "kinase activity. it", "activity. it is", "it is known", "is known that", "known that the", "that the src", "the src homology", "src homology region", "homology region 2", "2 sh2", "domain of", "of plc gamma", "plc gamma and", "gamma and of", "and of other", "of other signaling", "other signaling molecules", "molecules such", "such as gtpase", "as gtpase activating", "gtpase activating protein", "activating protein and", "protein and phosphatidylinositol", "and phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "3 kinase associated", "kinase associated p85", "p85 direct", "direct their binding", "their binding toward", "binding toward autophosphorylated", "toward autophosphorylated tyrosine", "autophosphorylated tyrosine residues", "tyrosine residues of", "residues of the", "of the fgfr.", "the fgfr. recruitment", "fgfr. recruitment of", "recruitment of plc", "plc gamma results", "gamma results in", "results in its", "in its phosphorylation", "its phosphorylation and", "phosphorylation and activation", "and activation by", "activation by the", "by the receptor.", "receptor. activated", "activated plc gamma", "plc gamma hydrolyzes", "gamma hydrolyzes phosphatidyl", "hydrolyzes phosphatidyl inositol", "phosphatidyl inositol 4", "inositol 4 5", "5 p2", "p2 to form", "to form the", "form the second", "the second messengers", "second messengers diacylglycerol", "diacylglycerol dag", "dag and", "ins 1", "1 4 5", "4 5 p3", "p3 which", "which stimulate calcium", "stimulate calcium release", "calcium release and", "release and activation", "and activation of", "activation of calcium/calmodulin", "of calcium/calmodulin dependent", "calcium/calmodulin dependent kinases.
              ", "c gamma plc", "gamma plc gamma", "plc gamma is", "gamma is a", "is a substrate of", "a substrate of the", "substrate of the fibroblast", "of the fibroblast growth", "the fibroblast growth factor", "fibroblast growth factor receptor", "factor receptor fgfr", "fgfr and other", "and other receptors with", "other receptors with tyrosine", "receptors with tyrosine kinase", "with tyrosine kinase activity.", "tyrosine kinase activity. it", "kinase activity. it is", "activity. it is known", "it is known that", "is known that the", "known that the src", "that the src homology", "the src homology region", "src homology region 2", "region 2 sh2", "2 sh2 domain", "sh2 domain of", "domain of plc", "of plc gamma and", "plc gamma and of", "gamma and of other", "and of other signaling", "of other signaling molecules", "signaling molecules such", "molecules such as", "such as gtpase activating", "as gtpase activating protein", "gtpase activating protein and", "activating protein and phosphatidylinositol", "protein and phosphatidylinositol 3", "and phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase associated", "3 kinase associated p85", "associated p85 direct", "p85 direct their", "direct their binding toward", "their binding toward autophosphorylated", "binding toward autophosphorylated tyrosine", "toward autophosphorylated tyrosine residues", "autophosphorylated tyrosine residues of", "tyrosine residues of the", "residues of the fgfr.", "of the fgfr. recruitment", "the fgfr. recruitment of", "fgfr. recruitment of plc", "recruitment of plc gamma", "of plc gamma results", "plc gamma results in", "gamma results in its", "results in its phosphorylation", "in its phosphorylation and", "its phosphorylation and activation", "phosphorylation and activation by", "and activation by the", "activation by the receptor.", "the receptor. activated", "receptor. activated plc", "activated plc gamma hydrolyzes", "plc gamma hydrolyzes phosphatidyl", "gamma hydrolyzes phosphatidyl inositol", "hydrolyzes phosphatidyl inositol 4", "phosphatidyl inositol 4 5", "4 5 p2", "5 p2 to", "p2 to form the", "to form the second", "form the second messengers", "the second messengers diacylglycerol", "messengers diacylglycerol dag", "dag and ins", "and ins 1", "ins 1 4", "1 4 5 p3", "5 p3 which", "p3 which stimulate", "which stimulate calcium release", "stimulate calcium release and", "calcium release and activation", "release and activation of", "and activation of calcium/calmodulin", "activation of calcium/calmodulin dependent", "of calcium/calmodulin dependent kinases.
              ", "phospholipase c gamma plc", "c gamma plc gamma", "plc gamma is a", "gamma is a substrate", "is a substrate of the", "a substrate of the fibroblast", "substrate of the fibroblast growth", "of the fibroblast growth factor", "the fibroblast growth factor receptor", "growth factor receptor fgfr", "receptor fgfr and", "fgfr and other receptors", "and other receptors with tyrosine", "other receptors with tyrosine kinase", "receptors with tyrosine kinase activity.", "with tyrosine kinase activity. it", "tyrosine kinase activity. it is", "kinase activity. it is known", "activity. it is known that", "it is known that the", "is known that the src", "known that the src homology", "that the src homology region", "the src homology region 2", "homology region 2 sh2", "region 2 sh2 domain", "sh2 domain of plc", "domain of plc gamma", "of plc gamma and of", "plc gamma and of other", "gamma and of other signaling", "and of other signaling molecules", "other signaling molecules such", "signaling molecules such as", "molecules such as gtpase", "such as gtpase activating protein", "as gtpase activating protein and", "gtpase activating protein and phosphatidylinositol", "activating protein and phosphatidylinositol 3", "protein and phosphatidylinositol 3 kinase", "and phosphatidylinositol 3 kinase associated", "phosphatidylinositol 3 kinase associated p85", "kinase associated p85 direct", "associated p85 direct their", "p85 direct their binding", "direct their binding toward autophosphorylated", "their binding toward autophosphorylated tyrosine", "binding toward autophosphorylated tyrosine residues", "toward autophosphorylated tyrosine residues of", "autophosphorylated tyrosine residues of the", "tyrosine residues of the fgfr.", "residues of the fgfr. recruitment", "of the fgfr. recruitment of", "the fgfr. recruitment of plc", "fgfr. recruitment of plc gamma", "recruitment of plc gamma results", "of plc gamma results in", "plc gamma results in its", "gamma results in its phosphorylation", "results in its phosphorylation and", "in its phosphorylation and activation", "its phosphorylation and activation by", "phosphorylation and activation by the", "and activation by the receptor.", "by the receptor. activated", "the receptor. activated plc", "receptor. activated plc gamma", "activated plc gamma hydrolyzes phosphatidyl", "plc gamma hydrolyzes phosphatidyl inositol", "gamma hydrolyzes phosphatidyl inositol 4", "hydrolyzes phosphatidyl inositol 4 5", "inositol 4 5 p2", "4 5 p2 to", "5 p2 to form", "p2 to form the second", "to form the second messengers", "form the second messengers diacylglycerol", "second messengers diacylglycerol dag", "diacylglycerol dag and", "and ins 1 4", "ins 1 4 5", "4 5 p3 which", "5 p3 which stimulate", "p3 which stimulate calcium", "which stimulate calcium release and", "stimulate calcium release and activation", "calcium release and activation of", "release and activation of calcium/calmodulin", "and activation of calcium/calmodulin dependent", "activation of calcium/calmodulin dependent kinases.
              " ] }, { "record_id": "GLY_000594_1_1040", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654687", "r hsa", "hsa 5654687", "r hsa 5654687" ] }, { "record_id": "GLY_000594_1_1040", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "downstream signaling", "signaling of", "of activated", "activated fgfr1", "downstream signaling of", "signaling of activated", "of activated fgfr1", "downstream signaling of activated", "signaling of activated fgfr1", "downstream signaling of activated fgfr1", "signaling via", "via fgfrs", "fgfrs is", "is mediated", "mediated via", "via direct", "direct recruitment", "recruitment of", "of signaling", "signaling proteins", "proteins that", "that bind", "bind to", "to tyrosine", "tyrosine auto", "auto phosphorylation", "phosphorylation sites", "sites on", "on the", "the activated", "activated receptor", "receptor and", "and via", "via closely", "closely linked", "linked docking", "docking proteins", "that become", "become tyrosine", "tyrosine phosphorylated", "phosphorylated in", "in response", "response to", "to fgf", "fgf stimulation", "stimulation and", "and form", "form a", "a complex", "complex with", "with additional", "additional complement", "complement of", "signaling proteins.", "proteins.

              the", "

              the activation", "activation loop", "loop in", "in the", "the catalytic", "catalytic domain", "domain of", "of fgfr", "fgfr maintains", "maintains the", "the ptk", "ptk domain", "domain in", "in an", "an inactive", "inactive or", "or low", "low activity", "activity state.", "state. the", "the activation", "loop of", "of fgfr1", "for instance", "contains two", "two tyrosine", "tyrosine residues", "residues that", "that must", "must be", "be autophosphorylated", "autophosphorylated for", "for maintaining", "maintaining the", "an active", "active state.", "state. in", "the autoinhibited", "autoinhibited configuration", "a kinase", "kinase invariant", "invariant proline", "proline residue", "residue at", "at the", "the c", "c terminal", "terminal end", "end of", "of the", "loop interferes", "interferes with", "with substrate", "substrate binding", "binding while", "while allowing", "allowing access", "access to", "to atp", "atp in", "the nucleotide", "nucleotide binding", "binding site.
              in", "site.
              in addition", "addition to", "to the", "catalytic ptk", "ptk core", "the cytoplasmic", "cytoplasmic domain", "fgfr contains", "contains several", "several regulatory", "regulatory sequences.", "sequences. the", "the juxtamembrane", "juxtamembrane domain", "of fgfrs", "is considerably", "considerably longer", "longer than", "than that", "that of", "of other", "other receptor", "receptor tyrosine", "tyrosine kinases.", "kinases. this", "this region", "region contains", "contains a", "a highly", "highly conserved", "conserved sequence", "sequence that", "that serves", "serves as", "as a", "a binding", "binding site", "site for", "for the", "the phosphotyrosine", "phosphotyrosine binding", "of frs2.", "frs2. a", "a variety", "variety of", "proteins are", "are phosphorylated", "including shc", "phospholipase c", "c gamma", "gamma and", "and frs2", "frs2 leading", "leading to", "to stimulation", "stimulation of", "of intracellular", "intracellular signaling", "signaling pathways", "pathways that", "that control", "control cell", "cell proliferation", "cell differentiation", "cell migration", "cell survival", "survival and", "and cell", "cell shape.", "signaling via fgfrs", "via fgfrs is", "fgfrs is mediated", "is mediated via", "mediated via direct", "via direct recruitment", "direct recruitment of", "recruitment of signaling", "of signaling proteins", "signaling proteins that", "proteins that bind", "that bind to", "bind to tyrosine", "to tyrosine auto", "tyrosine auto phosphorylation", "auto phosphorylation sites", "phosphorylation sites on", "sites on the", "on the activated", "the activated receptor", "activated receptor and", "receptor and via", "and via closely", "via closely linked", "closely linked docking", "linked docking proteins", "docking proteins that", "proteins that become", "that become tyrosine", "become tyrosine phosphorylated", "tyrosine phosphorylated in", "phosphorylated in response", "in response to", "response to fgf", "to fgf stimulation", "fgf stimulation and", "stimulation and form", "and form a", "form a complex", "a complex with", "complex with additional", "with additional complement", "additional complement of", "complement of signaling", "of signaling proteins.", "signaling proteins.

              the", "proteins.

              the activation", "

              the activation loop", "activation loop in", "loop in the", "in the catalytic", "the catalytic domain", "catalytic domain of", "domain of fgfr", "of fgfr maintains", "fgfr maintains the", "maintains the ptk", "the ptk domain", "ptk domain in", "domain in an", "in an inactive", "an inactive or", "inactive or low", "or low activity", "low activity state.", "activity state. the", "state. the activation", "the activation loop", "activation loop of", "loop of fgfr1", "fgfr1 for", "instance contains", "contains two tyrosine", "two tyrosine residues", "tyrosine residues that", "residues that must", "that must be", "must be autophosphorylated", "be autophosphorylated for", "autophosphorylated for maintaining", "for maintaining the", "maintaining the catalytic", "catalytic domain in", "in an active", "an active state.", "active state. in", "state. in the", "in the autoinhibited", "the autoinhibited configuration", "configuration a", "a kinase invariant", "kinase invariant proline", "invariant proline residue", "proline residue at", "residue at the", "at the c", "the c terminal", "c terminal end", "terminal end of", "end of the", "of the activation", "activation loop interferes", "loop interferes with", "interferes with substrate", "with substrate binding", "substrate binding while", "binding while allowing", "while allowing access", "allowing access to", "access to atp", "to atp in", "atp in the", "in the nucleotide", "the nucleotide binding", "nucleotide binding site.
              in", "binding site.
              in addition", "site.
              in addition to", "addition to the", "to the catalytic", "the catalytic ptk", "catalytic ptk core", "core the", "the cytoplasmic domain", "cytoplasmic domain of", "of fgfr contains", "fgfr contains several", "contains several regulatory", "several regulatory sequences.", "regulatory sequences. the", "sequences. the juxtamembrane", "the juxtamembrane domain", "juxtamembrane domain of", "domain of fgfrs", "of fgfrs is", "fgfrs is considerably", "is considerably longer", "considerably longer than", "longer than that", "than that of", "that of other", "of other receptor", "other receptor tyrosine", "receptor tyrosine kinases.", "tyrosine kinases. this", "kinases. this region", "this region contains", "region contains a", "contains a highly", "a highly conserved", "highly conserved sequence", "conserved sequence that", "sequence that serves", "that serves as", "serves as a", "as a binding", "a binding site", "binding site for", "site for the", "for the phosphotyrosine", "the phosphotyrosine binding", "binding ptb", "ptb domain", "domain of frs2.", "of frs2. a", "frs2. a variety", "a variety of", "variety of signaling", "signaling proteins are", "proteins are phosphorylated", "are phosphorylated in", "stimulation including", "shc phospholipase", "phospholipase c gamma", "c gamma and", "gamma and frs2", "and frs2 leading", "frs2 leading to", "leading to stimulation", "to stimulation of", "stimulation of intracellular", "of intracellular signaling", "intracellular signaling pathways", "signaling pathways that", "pathways that control", "that control cell", "control cell proliferation", "proliferation cell", "differentiation cell", "migration cell", "cell survival and", "survival and cell", "and cell shape.", "signaling via fgfrs is", "via fgfrs is mediated", "fgfrs is mediated via", "is mediated via direct", "mediated via direct recruitment", "via direct recruitment of", "direct recruitment of signaling", "recruitment of signaling proteins", "of signaling proteins that", "signaling proteins that bind", "proteins that bind to", "that bind to tyrosine", "bind to tyrosine auto", "to tyrosine auto phosphorylation", "tyrosine auto phosphorylation sites", "auto phosphorylation sites on", "phosphorylation sites on the", "sites on the activated", "on the activated receptor", "the activated receptor and", "activated receptor and via", "receptor and via closely", "and via closely linked", "via closely linked docking", "closely linked docking proteins", "linked docking proteins that", "docking proteins that become", "proteins that become tyrosine", "that become tyrosine phosphorylated", "become tyrosine phosphorylated in", "tyrosine phosphorylated in response", "phosphorylated in response to", "in response to fgf", "response to fgf stimulation", "to fgf stimulation and", "fgf stimulation and form", "stimulation and form a", "and form a complex", "form a complex with", "a complex with additional", "complex with additional complement", "with additional complement of", "additional complement of signaling", "complement of signaling proteins.", "of signaling proteins.

              the", "signaling proteins.

              the activation", "proteins.

              the activation loop", "

              the activation loop in", "activation loop in the", "loop in the catalytic", "in the catalytic domain", "the catalytic domain of", "catalytic domain of fgfr", "domain of fgfr maintains", "of fgfr maintains the", "fgfr maintains the ptk", "maintains the ptk domain", "the ptk domain in", "ptk domain in an", "domain in an inactive", "in an inactive or", "an inactive or low", "inactive or low activity", "or low activity state.", "low activity state. the", "activity state. the activation", "state. the activation loop", "the activation loop of", "activation loop of fgfr1", "of fgfr1 for", "fgfr1 for instance", "for instance contains", "instance contains two", "contains two tyrosine residues", "two tyrosine residues that", "tyrosine residues that must", "residues that must be", "that must be autophosphorylated", "must be autophosphorylated for", "be autophosphorylated for maintaining", "autophosphorylated for maintaining the", "for maintaining the catalytic", "maintaining the catalytic domain", "the catalytic domain in", "catalytic domain in an", "domain in an active", "in an active state.", "an active state. in", "active state. in the", "state. in the autoinhibited", "in the autoinhibited configuration", "autoinhibited configuration a", "configuration a kinase", "a kinase invariant proline", "kinase invariant proline residue", "invariant proline residue at", "proline residue at the", "residue at the c", "at the c terminal", "the c terminal end", "c terminal end of", "terminal end of the", "end of the activation", "of the activation loop", "the activation loop interferes", "activation loop interferes with", "loop interferes with substrate", "interferes with substrate binding", "with substrate binding while", "substrate binding while allowing", "binding while allowing access", "while allowing access to", "allowing access to atp", "access to atp in", "to atp in the", "atp in the nucleotide", "in the nucleotide binding", "the nucleotide binding site.
              in", "nucleotide binding site.
              in addition", "binding site.
              in addition to", "site.
              in addition to the", "addition to the catalytic", "to the catalytic ptk", "the catalytic ptk core", "ptk core the", "core the cytoplasmic", "the cytoplasmic domain of", "cytoplasmic domain of fgfr", "domain of fgfr contains", "of fgfr contains several", "fgfr contains several regulatory", "contains several regulatory sequences.", "several regulatory sequences. the", "regulatory sequences. the juxtamembrane", "sequences. the juxtamembrane domain", "the juxtamembrane domain of", "juxtamembrane domain of fgfrs", "domain of fgfrs is", "of fgfrs is considerably", "fgfrs is considerably longer", "is considerably longer than", "considerably longer than that", "longer than that of", "than that of other", "that of other receptor", "of other receptor tyrosine", "other receptor tyrosine kinases.", "receptor tyrosine kinases. this", "tyrosine kinases. this region", "kinases. this region contains", "this region contains a", "region contains a highly", "contains a highly conserved", "a highly conserved sequence", "highly conserved sequence that", "conserved sequence that serves", "sequence that serves as", "that serves as a", "serves as a binding", "as a binding site", "a binding site for", "binding site for the", "site for the phosphotyrosine", "for the phosphotyrosine binding", "phosphotyrosine binding ptb", "ptb domain of", "domain of frs2. a", "of frs2. a variety", "frs2. a variety of", "a variety of signaling", "variety of signaling proteins", "of signaling proteins are", "signaling proteins are phosphorylated", "proteins are phosphorylated in", "are phosphorylated in response", "fgf stimulation including", "stimulation including shc", "including shc phospholipase", "shc phospholipase c", "phospholipase c gamma and", "c gamma and frs2", "gamma and frs2 leading", "and frs2 leading to", "frs2 leading to stimulation", "leading to stimulation of", "to stimulation of intracellular", "stimulation of intracellular signaling", "of intracellular signaling pathways", "intracellular signaling pathways that", "signaling pathways that control", "pathways that control cell", "that control cell proliferation", "cell proliferation cell", "proliferation cell differentiation", "cell differentiation cell", "differentiation cell migration", "cell migration cell", "migration cell survival", "cell survival and cell", "survival and cell shape.", "signaling via fgfrs is mediated", "via fgfrs is mediated via", "fgfrs is mediated via direct", "is mediated via direct recruitment", "mediated via direct recruitment of", "via direct recruitment of signaling", "direct recruitment of signaling proteins", "recruitment of signaling proteins that", "of signaling proteins that bind", "signaling proteins that bind to", "proteins that bind to tyrosine", "that bind to tyrosine auto", "bind to tyrosine auto phosphorylation", "to tyrosine auto phosphorylation sites", "tyrosine auto phosphorylation sites on", "auto phosphorylation sites on the", "phosphorylation sites on the activated", "sites on the activated receptor", "on the activated receptor and", "the activated receptor and via", "activated receptor and via closely", "receptor and via closely linked", "and via closely linked docking", "via closely linked docking proteins", "closely linked docking proteins that", "linked docking proteins that become", "docking proteins that become tyrosine", "proteins that become tyrosine phosphorylated", "that become tyrosine phosphorylated in", "become tyrosine phosphorylated in response", "tyrosine phosphorylated in response to", "phosphorylated in response to fgf", "in response to fgf stimulation", "response to fgf stimulation and", "to fgf stimulation and form", "fgf stimulation and form a", "stimulation and form a complex", "and form a complex with", "form a complex with additional", "a complex with additional complement", "complex with additional complement of", "with additional complement of signaling", "additional complement of signaling proteins.", "complement of signaling proteins.

              the", "of signaling proteins.

              the activation", "signaling proteins.

              the activation loop", "proteins.

              the activation loop in", "

              the activation loop in the", "activation loop in the catalytic", "loop in the catalytic domain", "in the catalytic domain of", "the catalytic domain of fgfr", "catalytic domain of fgfr maintains", "domain of fgfr maintains the", "of fgfr maintains the ptk", "fgfr maintains the ptk domain", "maintains the ptk domain in", "the ptk domain in an", "ptk domain in an inactive", "domain in an inactive or", "in an inactive or low", "an inactive or low activity", "inactive or low activity state.", "or low activity state. the", "low activity state. the activation", "activity state. the activation loop", "state. the activation loop of", "the activation loop of fgfr1", "loop of fgfr1 for", "of fgfr1 for instance", "for instance contains two", "instance contains two tyrosine", "contains two tyrosine residues that", "two tyrosine residues that must", "tyrosine residues that must be", "residues that must be autophosphorylated", "that must be autophosphorylated for", "must be autophosphorylated for maintaining", "be autophosphorylated for maintaining the", "autophosphorylated for maintaining the catalytic", "for maintaining the catalytic domain", "maintaining the catalytic domain in", "the catalytic domain in an", "catalytic domain in an active", "domain in an active state.", "in an active state. in", "an active state. in the", "active state. in the autoinhibited", "state. in the autoinhibited configuration", "the autoinhibited configuration a", "autoinhibited configuration a kinase", "configuration a kinase invariant", "a kinase invariant proline residue", "kinase invariant proline residue at", "invariant proline residue at the", "proline residue at the c", "residue at the c terminal", "at the c terminal end", "the c terminal end of", "c terminal end of the", "terminal end of the activation", "end of the activation loop", "of the activation loop interferes", "the activation loop interferes with", "activation loop interferes with substrate", "loop interferes with substrate binding", "interferes with substrate binding while", "with substrate binding while allowing", "substrate binding while allowing access", "binding while allowing access to", "while allowing access to atp", "allowing access to atp in", "access to atp in the", "to atp in the nucleotide", "atp in the nucleotide binding", "in the nucleotide binding site.
              in", "the nucleotide binding site.
              in addition", "nucleotide binding site.
              in addition to", "binding site.
              in addition to the", "site.
              in addition to the catalytic", "addition to the catalytic ptk", "to the catalytic ptk core", "catalytic ptk core the", "ptk core the cytoplasmic", "core the cytoplasmic domain", "the cytoplasmic domain of fgfr", "cytoplasmic domain of fgfr contains", "domain of fgfr contains several", "of fgfr contains several regulatory", "fgfr contains several regulatory sequences.", "contains several regulatory sequences. the", "several regulatory sequences. the juxtamembrane", "regulatory sequences. the juxtamembrane domain", "sequences. the juxtamembrane domain of", "the juxtamembrane domain of fgfrs", "juxtamembrane domain of fgfrs is", "domain of fgfrs is considerably", "of fgfrs is considerably longer", "fgfrs is considerably longer than", "is considerably longer than that", "considerably longer than that of", "longer than that of other", "than that of other receptor", "that of other receptor tyrosine", "of other receptor tyrosine kinases.", "other receptor tyrosine kinases. this", "receptor tyrosine kinases. this region", "tyrosine kinases. this region contains", "kinases. this region contains a", "this region contains a highly", "region contains a highly conserved", "contains a highly conserved sequence", "a highly conserved sequence that", "highly conserved sequence that serves", "conserved sequence that serves as", "sequence that serves as a", "that serves as a binding", "serves as a binding site", "as a binding site for", "a binding site for the", "binding site for the phosphotyrosine", "site for the phosphotyrosine binding", "the phosphotyrosine binding ptb", "binding ptb domain", "ptb domain of frs2.", "domain of frs2. a variety", "of frs2. a variety of", "frs2. a variety of signaling", "a variety of signaling proteins", "variety of signaling proteins are", "of signaling proteins are phosphorylated", "signaling proteins are phosphorylated in", "proteins are phosphorylated in response", "are phosphorylated in response to", "to fgf stimulation including", "fgf stimulation including shc", "including shc phospholipase c", "shc phospholipase c gamma", "phospholipase c gamma and frs2", "c gamma and frs2 leading", "gamma and frs2 leading to", "and frs2 leading to stimulation", "frs2 leading to stimulation of", "leading to stimulation of intracellular", "to stimulation of intracellular signaling", "stimulation of intracellular signaling pathways", "of intracellular signaling pathways that", "intracellular signaling pathways that control", "signaling pathways that control cell", "pathways that control cell proliferation", "control cell proliferation cell", "cell proliferation cell differentiation", "cell differentiation cell migration", "cell migration cell survival", "migration cell survival and", "cell survival and cell shape." ] }, { "record_id": "GLY_000594_1_1041", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654688", "r hsa", "hsa 5654688", "r hsa 5654688" ] }, { "record_id": "GLY_000594_1_1041", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc mediated", "mediated cascade:fgfr1", "shc mediated cascade:fgfr1", "the exact", "exact role", "role of", "of shc1", "shc1 in", "in fgfr", "fgfr signaling", "signaling remains", "remains unclear.", "numerous studies", "studies have", "have shown", "shown that", "that the", "the p46", "p46 and", "and p52", "p52 isoforms", "isoforms of", "shc1 are", "are phosphorylated", "phosphorylated in", "in response", "response to", "to fgf", "fgf stimulation", "but direct", "direct interaction", "interaction with", "with the", "the receptor", "receptor has", "has not", "not been", "been demonstrated.", "demonstrated. co", "co precipitation", "precipitation of", "of p46", "p52 with", "the fgfr2", "fgfr2 iiic", "iiic receptor", "has been", "been reported", "but this", "this interaction", "interaction is", "is thought", "thought to", "to be", "be indirect", "possibly mediated", "mediated by", "by src.", "consistent with", "with this", "shc1 and", "and fgfr1", "fgfr1 iiic", "iiic is", "is seen", "seen in", "in mammalian", "mammalian cells", "cells expressing", "expressing v", "v src.", "the p66", "p66 isoform", "isoform of", "shc1 has", "has also", "also been", "been co", "co precipitated", "precipitated with", "with fgfr3", "this occurs", "occurs independently", "independently of", "of receptor", "receptor stimulation", "and the", "isoform not", "been shown", "shown to", "to undergo", "undergo fgf", "fgf dependent", "dependent phosphorylation.", "to associate", "associate with", "with grb2", "grb2 and", "and sos1", "sos1 in", "suggesting that", "the recruitment", "recruitment of", "shc1 may", "may contribute", "contribute to", "to activation", "activation of", "of the", "the mapk", "mapk cascade", "cascade downstream", "downstream of", "of fgfr.", "the exact role", "exact role of", "role of shc1", "of shc1 in", "shc1 in fgfr", "in fgfr signaling", "fgfr signaling remains", "signaling remains unclear.", "numerous studies have", "studies have shown", "have shown that", "shown that the", "that the p46", "the p46 and", "p46 and p52", "and p52 isoforms", "p52 isoforms of", "isoforms of shc1", "of shc1 are", "shc1 are phosphorylated", "are phosphorylated in", "phosphorylated in response", "in response to", "response to fgf", "to fgf stimulation", "stimulation but", "but direct interaction", "direct interaction with", "interaction with the", "with the receptor", "the receptor has", "receptor has not", "has not been", "not been demonstrated.", "been demonstrated. co", "demonstrated. co precipitation", "co precipitation of", "precipitation of p46", "of p46 and", "and p52 with", "p52 with the", "with the fgfr2", "the fgfr2 iiic", "fgfr2 iiic receptor", "iiic receptor has", "receptor has been", "has been reported", "reported but", "but this interaction", "this interaction is", "interaction is thought", "is thought to", "thought to be", "to be indirect", "indirect possibly", "possibly mediated by", "mediated by src.", "src. consistent", "consistent with this", "this co", "precipitation of shc1", "of shc1 and", "shc1 and fgfr1", "and fgfr1 iiic", "fgfr1 iiic is", "iiic is seen", "is seen in", "seen in mammalian", "in mammalian cells", "mammalian cells expressing", "cells expressing v", "expressing v src.", "src. the", "the p66 isoform", "p66 isoform of", "isoform of shc1", "of shc1 has", "shc1 has also", "has also been", "also been co", "been co precipitated", "co precipitated with", "precipitated with fgfr3", "fgfr3 but", "but this occurs", "this occurs independently", "occurs independently of", "independently of receptor", "of receptor stimulation", "stimulation and", "and the p66", "p66 isoform not", "isoform not been", "not been shown", "been shown to", "shown to undergo", "to undergo fgf", "undergo fgf dependent", "fgf dependent phosphorylation.", "phosphorylation. shc1", "shc1 has been", "has been shown", "shown to associate", "to associate with", "associate with grb2", "with grb2 and", "grb2 and sos1", "and sos1 in", "sos1 in response", "stimulation suggesting", "suggesting that the", "that the recruitment", "the recruitment of", "recruitment of shc1", "of shc1 may", "shc1 may contribute", "may contribute to", "contribute to activation", "to activation of", "activation of the", "of the mapk", "the mapk cascade", "mapk cascade downstream", "cascade downstream of", "downstream of fgfr.", "the exact role of", "exact role of shc1", "role of shc1 in", "of shc1 in fgfr", "shc1 in fgfr signaling", "in fgfr signaling remains", "fgfr signaling remains unclear.", "unclear. numerous", "numerous studies have shown", "studies have shown that", "have shown that the", "shown that the p46", "that the p46 and", "the p46 and p52", "p46 and p52 isoforms", "and p52 isoforms of", "p52 isoforms of shc1", "isoforms of shc1 are", "of shc1 are phosphorylated", "shc1 are phosphorylated in", "are phosphorylated in response", "phosphorylated in response to", "in response to fgf", "response to fgf stimulation", "fgf stimulation but", "stimulation but direct", "but direct interaction with", "direct interaction with the", "interaction with the receptor", "with the receptor has", "the receptor has not", "receptor has not been", "has not been demonstrated.", "not been demonstrated. co", "been demonstrated. co precipitation", "demonstrated. co precipitation of", "co precipitation of p46", "precipitation of p46 and", "of p46 and p52", "p46 and p52 with", "and p52 with the", "p52 with the fgfr2", "with the fgfr2 iiic", "the fgfr2 iiic receptor", "fgfr2 iiic receptor has", "iiic receptor has been", "receptor has been reported", "been reported but", "reported but this", "but this interaction is", "this interaction is thought", "interaction is thought to", "is thought to be", "thought to be indirect", "be indirect possibly", "indirect possibly mediated", "possibly mediated by src.", "by src. consistent", "src. consistent with", "with this co", "this co precipitation", "co precipitation of shc1", "precipitation of shc1 and", "of shc1 and fgfr1", "shc1 and fgfr1 iiic", "and fgfr1 iiic is", "fgfr1 iiic is seen", "iiic is seen in", "is seen in mammalian", "seen in mammalian cells", "in mammalian cells expressing", "mammalian cells expressing v", "cells expressing v src.", "v src. the", "src. the p66", "the p66 isoform of", "p66 isoform of shc1", "isoform of shc1 has", "of shc1 has also", "shc1 has also been", "has also been co", "also been co precipitated", "been co precipitated with", "co precipitated with fgfr3", "with fgfr3 but", "fgfr3 but this", "but this occurs independently", "this occurs independently of", "occurs independently of receptor", "independently of receptor stimulation", "receptor stimulation and", "stimulation and the", "and the p66 isoform", "the p66 isoform not", "p66 isoform not been", "isoform not been shown", "not been shown to", "been shown to undergo", "shown to undergo fgf", "to undergo fgf dependent", "undergo fgf dependent phosphorylation.", "dependent phosphorylation. shc1", "phosphorylation. shc1 has", "shc1 has been shown", "has been shown to", "been shown to associate", "shown to associate with", "to associate with grb2", "associate with grb2 and", "with grb2 and sos1", "grb2 and sos1 in", "and sos1 in response", "sos1 in response to", "fgf stimulation suggesting", "stimulation suggesting that", "suggesting that the recruitment", "that the recruitment of", "the recruitment of shc1", "recruitment of shc1 may", "of shc1 may contribute", "shc1 may contribute to", "may contribute to activation", "contribute to activation of", "to activation of the", "activation of the mapk", "of the mapk cascade", "the mapk cascade downstream", "mapk cascade downstream of", "cascade downstream of fgfr.", "the exact role of shc1", "exact role of shc1 in", "role of shc1 in fgfr", "of shc1 in fgfr signaling", "shc1 in fgfr signaling remains", "in fgfr signaling remains unclear.", "remains unclear. numerous", "unclear. numerous studies", "numerous studies have shown that", "studies have shown that the", "have shown that the p46", "shown that the p46 and", "that the p46 and p52", "the p46 and p52 isoforms", "p46 and p52 isoforms of", "and p52 isoforms of shc1", "p52 isoforms of shc1 are", "isoforms of shc1 are phosphorylated", "of shc1 are phosphorylated in", "shc1 are phosphorylated in response", "are phosphorylated in response to", "phosphorylated in response to fgf", "in response to fgf stimulation", "to fgf stimulation but", "fgf stimulation but direct", "stimulation but direct interaction", "but direct interaction with the", "direct interaction with the receptor", "interaction with the receptor has", "with the receptor has not", "the receptor has not been", "receptor has not been demonstrated.", "has not been demonstrated. co", "not been demonstrated. co precipitation", "been demonstrated. co precipitation of", "demonstrated. co precipitation of p46", "co precipitation of p46 and", "precipitation of p46 and p52", "of p46 and p52 with", "p46 and p52 with the", "and p52 with the fgfr2", "p52 with the fgfr2 iiic", "with the fgfr2 iiic receptor", "the fgfr2 iiic receptor has", "fgfr2 iiic receptor has been", "iiic receptor has been reported", "has been reported but", "been reported but this", "reported but this interaction", "but this interaction is thought", "this interaction is thought to", "interaction is thought to be", "is thought to be indirect", "to be indirect possibly", "be indirect possibly mediated", "indirect possibly mediated by", "mediated by src. consistent", "by src. consistent with", "src. consistent with this", "consistent with this co", "with this co precipitation", "this co precipitation of", "co precipitation of shc1 and", "precipitation of shc1 and fgfr1", "of shc1 and fgfr1 iiic", "shc1 and fgfr1 iiic is", "and fgfr1 iiic is seen", "fgfr1 iiic is seen in", "iiic is seen in mammalian", "is seen in mammalian cells", "seen in mammalian cells expressing", "in mammalian cells expressing v", "mammalian cells expressing v src.", "expressing v src. the", "v src. the p66", "src. the p66 isoform", "the p66 isoform of shc1", "p66 isoform of shc1 has", "isoform of shc1 has also", "of shc1 has also been", "shc1 has also been co", "has also been co precipitated", "also been co precipitated with", "been co precipitated with fgfr3", "precipitated with fgfr3 but", "with fgfr3 but this", "fgfr3 but this occurs", "but this occurs independently of", "this occurs independently of receptor", "occurs independently of receptor stimulation", "of receptor stimulation and", "receptor stimulation and the", "stimulation and the p66", "and the p66 isoform not", "the p66 isoform not been", "p66 isoform not been shown", "isoform not been shown to", "not been shown to undergo", "been shown to undergo fgf", "shown to undergo fgf dependent", "to undergo fgf dependent phosphorylation.", "fgf dependent phosphorylation. shc1", "dependent phosphorylation. shc1 has", "phosphorylation. shc1 has been", "shc1 has been shown to", "has been shown to associate", "been shown to associate with", "shown to associate with grb2", "to associate with grb2 and", "associate with grb2 and sos1", "with grb2 and sos1 in", "grb2 and sos1 in response", "and sos1 in response to", "sos1 in response to fgf", "to fgf stimulation suggesting", "fgf stimulation suggesting that", "stimulation suggesting that the", "suggesting that the recruitment of", "that the recruitment of shc1", "the recruitment of shc1 may", "recruitment of shc1 may contribute", "of shc1 may contribute to", "shc1 may contribute to activation", "may contribute to activation of", "contribute to activation of the", "to activation of the mapk", "activation of the mapk cascade", "of the mapk cascade downstream", "the mapk cascade downstream of", "mapk cascade downstream of fgfr." ] }, { "record_id": "GLY_000594_1_1042", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654689", "r hsa", "hsa 5654689", "r hsa 5654689" ] }, { "record_id": "GLY_000594_1_1042", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi 3k", "3k cascade:fgfr1", "pi 3k cascade:fgfr1", "the ability", "ability of", "of growth", "growth factors", "factors to", "to protect", "protect from", "from apoptosis", "apoptosis is", "is primarily", "primarily due", "due to", "to the", "the activation", "activation of", "of the", "the akt", "akt survival", "survival pathway.", "pathway. p", "p i", "i 3", "3 kinase", "kinase dependent", "dependent activation", "of pdk", "pdk leads", "leads to", "of akt", "akt which", "which in", "in turn", "turn affects", "affects the", "the activity", "activity or", "or expression", "expression of", "of pro", "pro apoptotic", "apoptotic factors", "which contribute", "contribute to", "to protection", "protection from", "from apoptosis.", "apoptosis. akt", "akt activation", "activation also", "also blocks", "blocks the", "activity of", "of gsk", "gsk 3b", "3b which", "which could", "could lead", "lead to", "to additional", "additional antiapoptotic", "antiapoptotic signals.", "the ability of", "ability of growth", "of growth factors", "growth factors to", "factors to protect", "to protect from", "protect from apoptosis", "from apoptosis is", "apoptosis is primarily", "is primarily due", "primarily due to", "due to the", "to the activation", "the activation of", "activation of the", "of the akt", "the akt survival", "akt survival pathway.", "survival pathway. p", "pathway. p i", "p i 3", "i 3 kinase", "3 kinase dependent", "kinase dependent activation", "dependent activation of", "activation of pdk", "of pdk leads", "pdk leads to", "leads to the", "activation of akt", "of akt which", "akt which in", "which in turn", "in turn affects", "turn affects the", "affects the activity", "the activity or", "activity or expression", "or expression of", "expression of pro", "of pro apoptotic", "pro apoptotic factors", "factors which", "which contribute to", "contribute to protection", "to protection from", "protection from apoptosis.", "from apoptosis. akt", "apoptosis. akt activation", "akt activation also", "activation also blocks", "also blocks the", "blocks the activity", "the activity of", "activity of gsk", "of gsk 3b", "gsk 3b which", "3b which could", "which could lead", "could lead to", "lead to additional", "to additional antiapoptotic", "additional antiapoptotic signals.", "the ability of growth", "ability of growth factors", "of growth factors to", "growth factors to protect", "factors to protect from", "to protect from apoptosis", "protect from apoptosis is", "from apoptosis is primarily", "apoptosis is primarily due", "is primarily due to", "primarily due to the", "due to the activation", "to the activation of", "the activation of the", "activation of the akt", "of the akt survival", "the akt survival pathway.", "akt survival pathway. p", "survival pathway. p i", "pathway. p i 3", "p i 3 kinase", "i 3 kinase dependent", "3 kinase dependent activation", "kinase dependent activation of", "dependent activation of pdk", "activation of pdk leads", "of pdk leads to", "pdk leads to the", "leads to the activation", "the activation of akt", "activation of akt which", "of akt which in", "akt which in turn", "which in turn affects", "in turn affects the", "turn affects the activity", "affects the activity or", "the activity or expression", "activity or expression of", "or expression of pro", "expression of pro apoptotic", "of pro apoptotic factors", "apoptotic factors which", "factors which contribute", "which contribute to protection", "contribute to protection from", "to protection from apoptosis.", "protection from apoptosis. akt", "from apoptosis. akt activation", "apoptosis. akt activation also", "akt activation also blocks", "activation also blocks the", "also blocks the activity", "blocks the activity of", "the activity of gsk", "activity of gsk 3b", "of gsk 3b which", "gsk 3b which could", "3b which could lead", "which could lead to", "could lead to additional", "lead to additional antiapoptotic", "to additional antiapoptotic signals.", "the ability of growth factors", "ability of growth factors to", "of growth factors to protect", "growth factors to protect from", "factors to protect from apoptosis", "to protect from apoptosis is", "protect from apoptosis is primarily", "from apoptosis is primarily due", "apoptosis is primarily due to", "is primarily due to the", "primarily due to the activation", "due to the activation of", "to the activation of the", "the activation of the akt", "activation of the akt survival", "of the akt survival pathway.", "the akt survival pathway. p", "akt survival pathway. p i", "survival pathway. p i 3", "pathway. p i 3 kinase", "p i 3 kinase dependent", "i 3 kinase dependent activation", "3 kinase dependent activation of", "kinase dependent activation of pdk", "dependent activation of pdk leads", "activation of pdk leads to", "of pdk leads to the", "pdk leads to the activation", "leads to the activation of", "to the activation of akt", "the activation of akt which", "activation of akt which in", "of akt which in turn", "akt which in turn affects", "which in turn affects the", "in turn affects the activity", "turn affects the activity or", "affects the activity or expression", "the activity or expression of", "activity or expression of pro", "or expression of pro apoptotic", "expression of pro apoptotic factors", "pro apoptotic factors which", "apoptotic factors which contribute", "factors which contribute to", "which contribute to protection from", "contribute to protection from apoptosis.", "to protection from apoptosis. akt", "protection from apoptosis. akt activation", "from apoptosis. akt activation also", "apoptosis. akt activation also blocks", "akt activation also blocks the", "activation also blocks the activity", "also blocks the activity of", "blocks the activity of gsk", "the activity of gsk 3b", "activity of gsk 3b which", "of gsk 3b which could", "gsk 3b which could lead", "3b which could lead to", "which could lead to additional", "could lead to additional antiapoptotic", "lead to additional antiapoptotic signals." ] }, { "record_id": "GLY_000594_1_1043", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654693", "r hsa", "hsa 5654693", "r hsa 5654693" ] }, { "record_id": "GLY_000594_1_1043", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "frs mediated", "mediated fgfr1", "fgfr1 signaling", "frs mediated fgfr1", "mediated fgfr1 signaling", "frs mediated fgfr1 signaling", "the frs", "frs family", "family of", "of scaffolding", "scaffolding adaptor", "adaptor proteins", "proteins has", "has two", "two members", "also known", "known as", "as frs2", "frs2 alpha", "and frs3", "as frs2beta", "frs2beta or", "or snt", "snt 2", "2 .", "activation of", "of fgfr", "fgfr tyrosine", "tyrosine kinase", "kinase allows", "allows frs", "frs proteins", "proteins to", "to become", "become phosphorylated", "phosphorylated on", "on tyrosine", "tyrosine residues", "residues and", "and then", "then bind", "bind to", "to the", "the adaptor", "adaptor grb2", "grb2 and", "and the", "the tyrosine", "tyrosine phosphatase", "phosphatase pptn11/shp2.", "pptn11 activates", "activates the", "the ras", "ras map", "map kinase", "kinase pathway", "pathway and", "and grb2", "grb2 activates", "pi 3", "3 kinase", "kinase and", "and ubiquitinations/degradation", "ubiquitinations/degradation pathways", "pathways by", "by binding", "binding to", "to sos", "gab1 and", "and cbl", "via the", "the sh3", "sh3 domains", "domains of", "of grb2.", "frs2 acts", "acts as", "as a", "a central", "central mediator", "mediator in", "in fgf", "fgf signaling", "signaling mainly", "mainly because", "because it", "it induces", "induces sustained", "sustained levels", "levels of", "of activation", "of erk", "erk with", "with ubiquitous", "ubiquitous expression.


              ", "the frs family", "frs family of", "family of scaffolding", "of scaffolding adaptor", "scaffolding adaptor proteins", "adaptor proteins has", "proteins has two", "has two members", "members frs2", "frs2 also", "also known as", "known as frs2", "as frs2 alpha", "alpha and", "frs3 also", "known as frs2beta", "as frs2beta or", "frs2beta or snt", "or snt 2", "snt 2 .", ". activation", "activation of fgfr", "of fgfr tyrosine", "fgfr tyrosine kinase", "tyrosine kinase allows", "kinase allows frs", "allows frs proteins", "frs proteins to", "proteins to become", "to become phosphorylated", "become phosphorylated on", "phosphorylated on tyrosine", "on tyrosine residues", "tyrosine residues and", "residues and then", "and then bind", "then bind to", "bind to the", "to the adaptor", "the adaptor grb2", "adaptor grb2 and", "grb2 and the", "and the tyrosine", "the tyrosine phosphatase", "tyrosine phosphatase pptn11/shp2.", "pptn11/shp2. subsequently", "subsequently pptn11", "pptn11 activates the", "activates the ras", "the ras map", "ras map kinase", "map kinase pathway", "kinase pathway and", "pathway and grb2", "and grb2 activates", "grb2 activates the", "pi 3 kinase", "3 kinase and", "kinase and ubiquitinations/degradation", "and ubiquitinations/degradation pathways", "ubiquitinations/degradation pathways by", "pathways by binding", "by binding to", "binding to sos", "sos gab1", "gab1 and cbl", "cbl respectively", "respectively via", "via the sh3", "the sh3 domains", "sh3 domains of", "domains of grb2.", "grb2. frs2", "frs2 acts as", "acts as a", "as a central", "a central mediator", "central mediator in", "mediator in fgf", "in fgf signaling", "fgf signaling mainly", "signaling mainly because", "mainly because it", "because it induces", "it induces sustained", "induces sustained levels", "sustained levels of", "levels of activation", "of activation of", "activation of erk", "of erk with", "erk with ubiquitous", "with ubiquitous expression.


              ", "the frs family of", "frs family of scaffolding", "family of scaffolding adaptor", "of scaffolding adaptor proteins", "scaffolding adaptor proteins has", "adaptor proteins has two", "proteins has two members", "two members frs2", "frs2 also known", "also known as frs2", "known as frs2 alpha", "frs2 alpha and", "alpha and frs3", "and frs3 also", "frs3 also known", "also known as frs2beta", "known as frs2beta or", "as frs2beta or snt", "frs2beta or snt 2", "or snt 2 .", "2 . activation", ". activation of", "activation of fgfr tyrosine", "of fgfr tyrosine kinase", "fgfr tyrosine kinase allows", "tyrosine kinase allows frs", "kinase allows frs proteins", "allows frs proteins to", "frs proteins to become", "proteins to become phosphorylated", "to become phosphorylated on", "become phosphorylated on tyrosine", "phosphorylated on tyrosine residues", "on tyrosine residues and", "tyrosine residues and then", "residues and then bind", "and then bind to", "then bind to the", "bind to the adaptor", "to the adaptor grb2", "the adaptor grb2 and", "adaptor grb2 and the", "grb2 and the tyrosine", "and the tyrosine phosphatase", "the tyrosine phosphatase pptn11/shp2.", "phosphatase pptn11/shp2. subsequently", "subsequently pptn11 activates", "pptn11 activates the ras", "activates the ras map", "the ras map kinase", "ras map kinase pathway", "map kinase pathway and", "kinase pathway and grb2", "pathway and grb2 activates", "and grb2 activates the", "grb2 activates the ras", "kinase pi", "pi 3 kinase and", "3 kinase and ubiquitinations/degradation", "kinase and ubiquitinations/degradation pathways", "and ubiquitinations/degradation pathways by", "ubiquitinations/degradation pathways by binding", "pathways by binding to", "by binding to sos", "to sos gab1", "sos gab1 and", "and cbl respectively", "respectively via the", "via the sh3 domains", "the sh3 domains of", "sh3 domains of grb2.", "of grb2. frs2", "grb2. frs2 acts", "frs2 acts as a", "acts as a central", "as a central mediator", "a central mediator in", "central mediator in fgf", "mediator in fgf signaling", "in fgf signaling mainly", "fgf signaling mainly because", "signaling mainly because it", "mainly because it induces", "because it induces sustained", "it induces sustained levels", "induces sustained levels of", "sustained levels of activation", "levels of activation of", "of activation of erk", "activation of erk with", "of erk with ubiquitous", "erk with ubiquitous expression.


              ", "the frs family of scaffolding", "frs family of scaffolding adaptor", "family of scaffolding adaptor proteins", "of scaffolding adaptor proteins has", "scaffolding adaptor proteins has two", "adaptor proteins has two members", "has two members frs2", "members frs2 also", "frs2 also known as", "also known as frs2 alpha", "as frs2 alpha and", "frs2 alpha and frs3", "and frs3 also known", "frs3 also known as", "also known as frs2beta or", "known as frs2beta or snt", "as frs2beta or snt 2", "frs2beta or snt 2 .", "snt 2 . activation", "2 . activation of", ". activation of fgfr", "activation of fgfr tyrosine kinase", "of fgfr tyrosine kinase allows", "fgfr tyrosine kinase allows frs", "tyrosine kinase allows frs proteins", "kinase allows frs proteins to", "allows frs proteins to become", "frs proteins to become phosphorylated", "proteins to become phosphorylated on", "to become phosphorylated on tyrosine", "become phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues and", "on tyrosine residues and then", "tyrosine residues and then bind", "residues and then bind to", "and then bind to the", "then bind to the adaptor", "bind to the adaptor grb2", "to the adaptor grb2 and", "the adaptor grb2 and the", "adaptor grb2 and the tyrosine", "grb2 and the tyrosine phosphatase", "and the tyrosine phosphatase pptn11/shp2.", "tyrosine phosphatase pptn11/shp2. subsequently", "pptn11/shp2. subsequently pptn11", "subsequently pptn11 activates the", "pptn11 activates the ras map", "activates the ras map kinase", "the ras map kinase pathway", "ras map kinase pathway and", "map kinase pathway and grb2", "kinase pathway and grb2 activates", "pathway and grb2 activates the", "and grb2 activates the ras", "grb2 activates the ras map", "map kinase pi", "kinase pi 3", "pi 3 kinase and ubiquitinations/degradation", "3 kinase and ubiquitinations/degradation pathways", "kinase and ubiquitinations/degradation pathways by", "and ubiquitinations/degradation pathways by binding", "ubiquitinations/degradation pathways by binding to", "pathways by binding to sos", "binding to sos gab1", "to sos gab1 and", "sos gab1 and cbl", "gab1 and cbl respectively", "cbl respectively via", "respectively via the sh3", "via the sh3 domains of", "the sh3 domains of grb2.", "domains of grb2. frs2", "of grb2. frs2 acts", "grb2. frs2 acts as", "frs2 acts as a central", "acts as a central mediator", "as a central mediator in", "a central mediator in fgf", "central mediator in fgf signaling", "mediator in fgf signaling mainly", "in fgf signaling mainly because", "fgf signaling mainly because it", "signaling mainly because it induces", "mainly because it induces sustained", "because it induces sustained levels", "it induces sustained levels of", "induces sustained levels of activation", "sustained levels of activation of", "levels of activation of erk", "of activation of erk with", "activation of erk with ubiquitous", "of erk with ubiquitous expression.


              " ] }, { "record_id": "GLY_000594_1_1044", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654695", "r hsa", "hsa 5654695", "r hsa 5654695" ] }, { "record_id": "GLY_000594_1_1044", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi 3k", "3k cascade:fgfr2", "pi 3k cascade:fgfr2", "the ability", "ability of", "of growth", "growth factors", "factors to", "to protect", "protect from", "from apoptosis", "apoptosis is", "is primarily", "primarily due", "due to", "to the", "the activation", "activation of", "of the", "the akt", "akt survival", "survival pathway.", "pathway. p", "p i", "i 3", "3 kinase", "kinase dependent", "dependent activation", "of pdk", "pdk leads", "leads to", "of akt", "akt which", "which in", "in turn", "turn affects", "affects the", "the activity", "activity or", "or expression", "expression of", "of pro", "pro apoptotic", "apoptotic factors", "which contribute", "contribute to", "to protection", "protection from", "from apoptosis.", "apoptosis. akt", "akt activation", "activation also", "also blocks", "blocks the", "activity of", "of gsk", "gsk 3b", "3b which", "which could", "could lead", "lead to", "to additional", "additional antiapoptotic", "antiapoptotic signals.", "the ability of", "ability of growth", "of growth factors", "growth factors to", "factors to protect", "to protect from", "protect from apoptosis", "from apoptosis is", "apoptosis is primarily", "is primarily due", "primarily due to", "due to the", "to the activation", "the activation of", "activation of the", "of the akt", "the akt survival", "akt survival pathway.", "survival pathway. p", "pathway. p i", "p i 3", "i 3 kinase", "3 kinase dependent", "kinase dependent activation", "dependent activation of", "activation of pdk", "of pdk leads", "pdk leads to", "leads to the", "activation of akt", "of akt which", "akt which in", "which in turn", "in turn affects", "turn affects the", "affects the activity", "the activity or", "activity or expression", "or expression of", "expression of pro", "of pro apoptotic", "pro apoptotic factors", "factors which", "which contribute to", "contribute to protection", "to protection from", "protection from apoptosis.", "from apoptosis. akt", "apoptosis. akt activation", "akt activation also", "activation also blocks", "also blocks the", "blocks the activity", "the activity of", "activity of gsk", "of gsk 3b", "gsk 3b which", "3b which could", "which could lead", "could lead to", "lead to additional", "to additional antiapoptotic", "additional antiapoptotic signals.", "the ability of growth", "ability of growth factors", "of growth factors to", "growth factors to protect", "factors to protect from", "to protect from apoptosis", "protect from apoptosis is", "from apoptosis is primarily", "apoptosis is primarily due", "is primarily due to", "primarily due to the", "due to the activation", "to the activation of", "the activation of the", "activation of the akt", "of the akt survival", "the akt survival pathway.", "akt survival pathway. p", "survival pathway. p i", "pathway. p i 3", "p i 3 kinase", "i 3 kinase dependent", "3 kinase dependent activation", "kinase dependent activation of", "dependent activation of pdk", "activation of pdk leads", "of pdk leads to", "pdk leads to the", "leads to the activation", "the activation of akt", "activation of akt which", "of akt which in", "akt which in turn", "which in turn affects", "in turn affects the", "turn affects the activity", "affects the activity or", "the activity or expression", "activity or expression of", "or expression of pro", "expression of pro apoptotic", "of pro apoptotic factors", "apoptotic factors which", "factors which contribute", "which contribute to protection", "contribute to protection from", "to protection from apoptosis.", "protection from apoptosis. akt", "from apoptosis. akt activation", "apoptosis. akt activation also", "akt activation also blocks", "activation also blocks the", "also blocks the activity", "blocks the activity of", "the activity of gsk", "activity of gsk 3b", "of gsk 3b which", "gsk 3b which could", "3b which could lead", "which could lead to", "could lead to additional", "lead to additional antiapoptotic", "to additional antiapoptotic signals.", "the ability of growth factors", "ability of growth factors to", "of growth factors to protect", "growth factors to protect from", "factors to protect from apoptosis", "to protect from apoptosis is", "protect from apoptosis is primarily", "from apoptosis is primarily due", "apoptosis is primarily due to", "is primarily due to the", "primarily due to the activation", "due to the activation of", "to the activation of the", "the activation of the akt", "activation of the akt survival", "of the akt survival pathway.", "the akt survival pathway. p", "akt survival pathway. p i", "survival pathway. p i 3", "pathway. p i 3 kinase", "p i 3 kinase dependent", "i 3 kinase dependent activation", "3 kinase dependent activation of", "kinase dependent activation of pdk", "dependent activation of pdk leads", "activation of pdk leads to", "of pdk leads to the", "pdk leads to the activation", "leads to the activation of", "to the activation of akt", "the activation of akt which", "activation of akt which in", "of akt which in turn", "akt which in turn affects", "which in turn affects the", "in turn affects the activity", "turn affects the activity or", "affects the activity or expression", "the activity or expression of", "activity or expression of pro", "or expression of pro apoptotic", "expression of pro apoptotic factors", "pro apoptotic factors which", "apoptotic factors which contribute", "factors which contribute to", "which contribute to protection from", "contribute to protection from apoptosis.", "to protection from apoptosis. akt", "protection from apoptosis. akt activation", "from apoptosis. akt activation also", "apoptosis. akt activation also blocks", "akt activation also blocks the", "activation also blocks the activity", "also blocks the activity of", "blocks the activity of gsk", "the activity of gsk 3b", "activity of gsk 3b which", "of gsk 3b which could", "gsk 3b which could lead", "3b which could lead to", "which could lead to additional", "could lead to additional antiapoptotic", "lead to additional antiapoptotic signals." ] }, { "record_id": "GLY_000594_1_1045", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654699", "r hsa", "hsa 5654699", "r hsa 5654699" ] }, { "record_id": "GLY_000594_1_1045", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc mediated", "mediated cascade:fgfr2", "shc mediated cascade:fgfr2", "the exact", "exact role", "role of", "of shc1", "shc1 in", "in fgfr", "fgfr signaling", "signaling remains", "remains unclear.", "numerous studies", "studies have", "have shown", "shown that", "that the", "the p46", "p46 and", "and p52", "p52 isoforms", "isoforms of", "shc1 are", "are phosphorylated", "phosphorylated in", "in response", "response to", "to fgf", "fgf stimulation", "but direct", "direct interaction", "interaction with", "with the", "the receptor", "receptor has", "has not", "not been", "been demonstrated.", "demonstrated. co", "co precipitation", "precipitation of", "of p46", "p52 with", "the fgfr2", "fgfr2 iiic", "iiic receptor", "has been", "been reported", "but this", "this interaction", "interaction is", "is thought", "thought to", "to be", "be indirect", "possibly mediated", "mediated by", "by src.", "consistent with", "with this", "shc1 and", "and fgfr1", "fgfr1 iiic", "iiic is", "is seen", "seen in", "in mammalian", "mammalian cells", "cells expressing", "expressing v", "v src.", "the p66", "p66 isoform", "isoform of", "shc1 has", "has also", "also been", "been co", "co precipitated", "precipitated with", "with fgfr3", "this occurs", "occurs independently", "independently of", "of receptor", "receptor stimulation", "and the", "isoform not", "been shown", "shown to", "to undergo", "undergo fgf", "fgf dependent", "dependent phosphorylation.", "to associate", "associate with", "with grb2", "grb2 and", "and sos1", "sos1 in", "suggesting that", "the recruitment", "recruitment of", "shc1 may", "may contribute", "contribute to", "to activation", "activation of", "of the", "the mapk", "mapk cascade", "cascade downstream", "downstream of", "of fgfr.", "the exact role", "exact role of", "role of shc1", "of shc1 in", "shc1 in fgfr", "in fgfr signaling", "fgfr signaling remains", "signaling remains unclear.", "numerous studies have", "studies have shown", "have shown that", "shown that the", "that the p46", "the p46 and", "p46 and p52", "and p52 isoforms", "p52 isoforms of", "isoforms of shc1", "of shc1 are", "shc1 are phosphorylated", "are phosphorylated in", "phosphorylated in response", "in response to", "response to fgf", "to fgf stimulation", "stimulation but", "but direct interaction", "direct interaction with", "interaction with the", "with the receptor", "the receptor has", "receptor has not", "has not been", "not been demonstrated.", "been demonstrated. co", "demonstrated. co precipitation", "co precipitation of", "precipitation of p46", "of p46 and", "and p52 with", "p52 with the", "with the fgfr2", "the fgfr2 iiic", "fgfr2 iiic receptor", "iiic receptor has", "receptor has been", "has been reported", "reported but", "but this interaction", "this interaction is", "interaction is thought", "is thought to", "thought to be", "to be indirect", "indirect possibly", "possibly mediated by", "mediated by src.", "src. consistent", "consistent with this", "this co", "precipitation of shc1", "of shc1 and", "shc1 and fgfr1", "and fgfr1 iiic", "fgfr1 iiic is", "iiic is seen", "is seen in", "seen in mammalian", "in mammalian cells", "mammalian cells expressing", "cells expressing v", "expressing v src.", "src. the", "the p66 isoform", "p66 isoform of", "isoform of shc1", "of shc1 has", "shc1 has also", "has also been", "also been co", "been co precipitated", "co precipitated with", "precipitated with fgfr3", "fgfr3 but", "but this occurs", "this occurs independently", "occurs independently of", "independently of receptor", "of receptor stimulation", "stimulation and", "and the p66", "p66 isoform not", "isoform not been", "not been shown", "been shown to", "shown to undergo", "to undergo fgf", "undergo fgf dependent", "fgf dependent phosphorylation.", "phosphorylation. shc1", "shc1 has been", "has been shown", "shown to associate", "to associate with", "associate with grb2", "with grb2 and", "grb2 and sos1", "and sos1 in", "sos1 in response", "stimulation suggesting", "suggesting that the", "that the recruitment", "the recruitment of", "recruitment of shc1", "of shc1 may", "shc1 may contribute", "may contribute to", "contribute to activation", "to activation of", "activation of the", "of the mapk", "the mapk cascade", "mapk cascade downstream", "cascade downstream of", "downstream of fgfr.", "the exact role of", "exact role of shc1", "role of shc1 in", "of shc1 in fgfr", "shc1 in fgfr signaling", "in fgfr signaling remains", "fgfr signaling remains unclear.", "unclear. numerous", "numerous studies have shown", "studies have shown that", "have shown that the", "shown that the p46", "that the p46 and", "the p46 and p52", "p46 and p52 isoforms", "and p52 isoforms of", "p52 isoforms of shc1", "isoforms of shc1 are", "of shc1 are phosphorylated", "shc1 are phosphorylated in", "are phosphorylated in response", "phosphorylated in response to", "in response to fgf", "response to fgf stimulation", "fgf stimulation but", "stimulation but direct", "but direct interaction with", "direct interaction with the", "interaction with the receptor", "with the receptor has", "the receptor has not", "receptor has not been", "has not been demonstrated.", "not been demonstrated. co", "been demonstrated. co precipitation", "demonstrated. co precipitation of", "co precipitation of p46", "precipitation of p46 and", "of p46 and p52", "p46 and p52 with", "and p52 with the", "p52 with the fgfr2", "with the fgfr2 iiic", "the fgfr2 iiic receptor", "fgfr2 iiic receptor has", "iiic receptor has been", "receptor has been reported", "been reported but", "reported but this", "but this interaction is", "this interaction is thought", "interaction is thought to", "is thought to be", "thought to be indirect", "be indirect possibly", "indirect possibly mediated", "possibly mediated by src.", "by src. consistent", "src. consistent with", "with this co", "this co precipitation", "co precipitation of shc1", "precipitation of shc1 and", "of shc1 and fgfr1", "shc1 and fgfr1 iiic", "and fgfr1 iiic is", "fgfr1 iiic is seen", "iiic is seen in", "is seen in mammalian", "seen in mammalian cells", "in mammalian cells expressing", "mammalian cells expressing v", "cells expressing v src.", "v src. the", "src. the p66", "the p66 isoform of", "p66 isoform of shc1", "isoform of shc1 has", "of shc1 has also", "shc1 has also been", "has also been co", "also been co precipitated", "been co precipitated with", "co precipitated with fgfr3", "with fgfr3 but", "fgfr3 but this", "but this occurs independently", "this occurs independently of", "occurs independently of receptor", "independently of receptor stimulation", "receptor stimulation and", "stimulation and the", "and the p66 isoform", "the p66 isoform not", "p66 isoform not been", "isoform not been shown", "not been shown to", "been shown to undergo", "shown to undergo fgf", "to undergo fgf dependent", "undergo fgf dependent phosphorylation.", "dependent phosphorylation. shc1", "phosphorylation. shc1 has", "shc1 has been shown", "has been shown to", "been shown to associate", "shown to associate with", "to associate with grb2", "associate with grb2 and", "with grb2 and sos1", "grb2 and sos1 in", "and sos1 in response", "sos1 in response to", "fgf stimulation suggesting", "stimulation suggesting that", "suggesting that the recruitment", "that the recruitment of", "the recruitment of shc1", "recruitment of shc1 may", "of shc1 may contribute", "shc1 may contribute to", "may contribute to activation", "contribute to activation of", "to activation of the", "activation of the mapk", "of the mapk cascade", "the mapk cascade downstream", "mapk cascade downstream of", "cascade downstream of fgfr.", "the exact role of shc1", "exact role of shc1 in", "role of shc1 in fgfr", "of shc1 in fgfr signaling", "shc1 in fgfr signaling remains", "in fgfr signaling remains unclear.", "remains unclear. numerous", "unclear. numerous studies", "numerous studies have shown that", "studies have shown that the", "have shown that the p46", "shown that the p46 and", "that the p46 and p52", "the p46 and p52 isoforms", "p46 and p52 isoforms of", "and p52 isoforms of shc1", "p52 isoforms of shc1 are", "isoforms of shc1 are phosphorylated", "of shc1 are 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interaction", "but this interaction is thought", "this interaction is thought to", "interaction is thought to be", "is thought to be indirect", "to be indirect possibly", "be indirect possibly mediated", "indirect possibly mediated by", "mediated by src. consistent", "by src. consistent with", "src. consistent with this", "consistent with this co", "with this co precipitation", "this co precipitation of", "co precipitation of shc1 and", "precipitation of shc1 and fgfr1", "of shc1 and fgfr1 iiic", "shc1 and fgfr1 iiic is", "and fgfr1 iiic is seen", "fgfr1 iiic is seen in", "iiic is seen in mammalian", "is seen in mammalian cells", "seen in mammalian cells expressing", "in mammalian cells expressing v", "mammalian cells expressing v src.", "expressing v src. the", "v src. the p66", "src. the p66 isoform", "the p66 isoform of shc1", "p66 isoform of shc1 has", "isoform of shc1 has also", "of shc1 has also been", "shc1 has also been co", "has also been co precipitated", "also been co precipitated with", "been co precipitated with fgfr3", "precipitated with fgfr3 but", "with fgfr3 but this", "fgfr3 but this occurs", "but this occurs independently of", "this occurs independently of receptor", "occurs independently of receptor stimulation", "of receptor stimulation and", "receptor stimulation and the", "stimulation and the p66", "and the p66 isoform not", "the p66 isoform not been", "p66 isoform not been shown", "isoform not been shown to", "not been shown to undergo", "been shown to undergo fgf", "shown to undergo fgf dependent", "to undergo fgf dependent phosphorylation.", "fgf dependent phosphorylation. shc1", "dependent phosphorylation. shc1 has", "phosphorylation. shc1 has been", "shc1 has been shown to", "has been shown to associate", "been shown to associate with", "shown to associate with grb2", "to associate with grb2 and", "associate with grb2 and sos1", "with grb2 and sos1 in", "grb2 and sos1 in response", "and sos1 in response to", "sos1 in response to fgf", "to fgf stimulation suggesting", "fgf stimulation suggesting that", "stimulation suggesting that the", "suggesting that the recruitment of", "that the recruitment of shc1", "the recruitment of shc1 may", "recruitment of shc1 may contribute", "of shc1 may contribute to", "shc1 may contribute to activation", "may contribute to activation of", "contribute to activation of the", "to activation of the mapk", "activation of the mapk cascade", "of the mapk cascade downstream", "the mapk cascade downstream of", "mapk cascade downstream of fgfr." ] }, { "record_id": "GLY_000594_1_1046", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654700", "r hsa", "hsa 5654700", "r hsa 5654700" ] }, { "record_id": "GLY_000594_1_1046", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "frs mediated", "mediated fgfr2", "fgfr2 signaling", "frs mediated fgfr2", "mediated fgfr2 signaling", "frs mediated fgfr2 signaling", "the frs", "frs family", "family of", "of scaffolding", "scaffolding adaptor", "adaptor proteins", "proteins has", "has two", "two members", "also known", "known as", "as frs2", "frs2 alpha", "and frs3", "as frs2beta", "frs2beta or", "or snt", "snt 2", "2 .", "activation of", "of fgfr", "fgfr tyrosine", "tyrosine kinase", "kinase allows", "allows frs", "frs proteins", "proteins to", "to become", "become phosphorylated", "phosphorylated on", "on tyrosine", "tyrosine residues", "residues and", "and then", "then bind", "bind to", "to the", "the adaptor", "adaptor grb2", "grb2 and", "and the", "the tyrosine", "tyrosine phosphatase", "phosphatase pptn11/shp2.", "pptn11 activates", "activates the", "the ras", "ras map", "map kinase", "kinase pathway", "pathway and", "and grb2", "grb2 activates", "pi 3", "3 kinase", "kinase and", "and ubiquitinations/degradation", "ubiquitinations/degradation pathways", "pathways by", "by binding", "binding to", "to sos", "gab1 and", "and cbl", "via the", "the sh3", "sh3 domains", "domains of", "of grb2.", "frs2 acts", "acts as", "as a", "a central", "central mediator", "mediator in", "in fgf", "fgf signaling", "signaling mainly", "mainly because", "because it", "it induces", "induces sustained", "sustained levels", "levels of", "of activation", "of erk", "erk with", "with ubiquitous", "ubiquitous expression.


              ", "the frs family", "frs family of", "family of scaffolding", "of scaffolding adaptor", "scaffolding adaptor proteins", "adaptor proteins has", "proteins has two", "has two members", "members frs2", "frs2 also", "also known as", "known as frs2", "as frs2 alpha", "alpha and", "frs3 also", "known as frs2beta", "as frs2beta or", "frs2beta or snt", "or snt 2", "snt 2 .", ". activation", "activation of fgfr", "of fgfr tyrosine", "fgfr tyrosine kinase", "tyrosine kinase allows", "kinase allows frs", "allows frs proteins", "frs proteins to", "proteins to become", "to become phosphorylated", "become phosphorylated on", "phosphorylated on tyrosine", "on tyrosine residues", "tyrosine residues and", "residues and then", "and then bind", "then bind to", "bind to the", "to the adaptor", "the adaptor grb2", "adaptor grb2 and", "grb2 and the", "and the tyrosine", "the tyrosine phosphatase", "tyrosine phosphatase pptn11/shp2.", "pptn11/shp2. subsequently", "subsequently pptn11", "pptn11 activates the", "activates the ras", "the ras map", "ras map kinase", "map kinase pathway", "kinase pathway and", "pathway and grb2", "and grb2 activates", "grb2 activates the", "pi 3 kinase", "3 kinase and", "kinase and ubiquitinations/degradation", "and ubiquitinations/degradation pathways", "ubiquitinations/degradation pathways by", "pathways by binding", "by binding to", "binding to sos", "sos gab1", "gab1 and cbl", "cbl respectively", "respectively via", "via the sh3", "the sh3 domains", "sh3 domains of", "domains of grb2.", "grb2. frs2", "frs2 acts as", "acts as a", "as a central", "a central mediator", "central mediator in", "mediator in fgf", "in fgf signaling", "fgf signaling mainly", "signaling mainly because", "mainly because it", "because it induces", "it induces sustained", "induces sustained levels", "sustained levels of", "levels of activation", "of activation of", "activation of erk", "of erk with", "erk with ubiquitous", "with ubiquitous expression.


              ", "the frs family of", "frs family of scaffolding", "family of scaffolding adaptor", "of scaffolding adaptor proteins", "scaffolding adaptor proteins has", "adaptor proteins has two", "proteins has two members", "two members frs2", "frs2 also known", "also known as frs2", "known as frs2 alpha", "frs2 alpha and", "alpha and frs3", "and frs3 also", "frs3 also known", "also known as frs2beta", "known as frs2beta or", "as frs2beta or snt", "frs2beta or snt 2", "or snt 2 .", "2 . activation", ". activation of", "activation of fgfr tyrosine", "of fgfr tyrosine kinase", "fgfr tyrosine kinase allows", "tyrosine kinase allows frs", "kinase allows frs proteins", "allows frs proteins to", "frs proteins to become", "proteins to become phosphorylated", "to become phosphorylated on", "become phosphorylated on tyrosine", "phosphorylated on tyrosine residues", "on tyrosine residues and", "tyrosine residues and then", "residues and then bind", "and then bind to", "then bind to the", "bind to the adaptor", "to the adaptor grb2", "the adaptor grb2 and", "adaptor grb2 and the", "grb2 and the tyrosine", "and the tyrosine phosphatase", "the tyrosine phosphatase pptn11/shp2.", "phosphatase pptn11/shp2. subsequently", "subsequently pptn11 activates", "pptn11 activates the ras", "activates the ras map", "the ras map kinase", "ras map kinase pathway", "map kinase pathway and", "kinase pathway and grb2", "pathway and grb2 activates", "and grb2 activates the", "grb2 activates the ras", "kinase pi", "pi 3 kinase and", "3 kinase and ubiquitinations/degradation", "kinase and ubiquitinations/degradation pathways", "and ubiquitinations/degradation pathways by", "ubiquitinations/degradation pathways by binding", "pathways by binding to", "by binding to sos", "to sos gab1", "sos gab1 and", "and cbl respectively", "respectively via the", "via the sh3 domains", "the sh3 domains of", "sh3 domains of grb2.", "of grb2. frs2", "grb2. frs2 acts", "frs2 acts as a", "acts as a central", "as a central mediator", "a central mediator in", "central mediator in fgf", "mediator in fgf signaling", "in fgf signaling mainly", "fgf signaling mainly because", "signaling mainly because it", "mainly because it induces", "because it induces sustained", "it induces sustained levels", "induces sustained levels of", "sustained levels of activation", "levels of activation of", "of activation of erk", "activation of erk with", "of erk with ubiquitous", "erk with ubiquitous expression.


              ", "the frs family of scaffolding", "frs family of scaffolding adaptor", "family of scaffolding adaptor proteins", "of scaffolding adaptor proteins has", "scaffolding adaptor proteins has two", "adaptor proteins has two members", "has two members frs2", "members frs2 also", "frs2 also known as", "also known as frs2 alpha", "as frs2 alpha and", "frs2 alpha and frs3", "and frs3 also known", "frs3 also known as", "also known as frs2beta or", "known as frs2beta or snt", "as frs2beta or snt 2", "frs2beta or snt 2 .", "snt 2 . activation", "2 . activation of", ". activation of fgfr", "activation of fgfr tyrosine kinase", "of fgfr tyrosine kinase allows", "fgfr tyrosine kinase allows frs", "tyrosine kinase allows frs proteins", "kinase allows frs proteins to", "allows frs proteins to become", "frs proteins to become phosphorylated", "proteins to become phosphorylated on", "to become phosphorylated on tyrosine", "become phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues and", "on tyrosine residues and then", "tyrosine residues and then bind", "residues and then bind to", "and then bind to the", "then bind to the adaptor", "bind to the adaptor grb2", "to the adaptor grb2 and", "the adaptor grb2 and the", "adaptor grb2 and the tyrosine", "grb2 and the tyrosine phosphatase", "and the tyrosine phosphatase pptn11/shp2.", "tyrosine phosphatase pptn11/shp2. subsequently", "pptn11/shp2. subsequently pptn11", "subsequently pptn11 activates the", "pptn11 activates the ras map", "activates the ras map kinase", "the ras map kinase pathway", "ras map kinase pathway and", "map kinase pathway and grb2", "kinase pathway and grb2 activates", "pathway and grb2 activates the", "and grb2 activates the ras", "grb2 activates the ras map", "map kinase pi", "kinase pi 3", "pi 3 kinase and ubiquitinations/degradation", "3 kinase and ubiquitinations/degradation pathways", "kinase and ubiquitinations/degradation pathways by", "and ubiquitinations/degradation pathways by binding", "ubiquitinations/degradation pathways by binding to", "pathways by binding to sos", "binding to sos gab1", "to sos gab1 and", "sos gab1 and cbl", "gab1 and cbl respectively", "cbl respectively via", "respectively via the sh3", "via the sh3 domains of", "the sh3 domains of grb2.", "domains of grb2. frs2", "of grb2. frs2 acts", "grb2. frs2 acts as", "frs2 acts as a central", "acts as a central mediator", "as a central mediator in", "a central mediator in fgf", "central mediator in fgf signaling", "mediator in fgf signaling mainly", "in fgf signaling mainly because", "fgf signaling mainly because it", "signaling mainly because it induces", "mainly because it induces sustained", "because it induces sustained levels", "it induces sustained levels of", "induces sustained levels of activation", "sustained levels of activation of", "levels of activation of erk", "of activation of erk with", "activation of erk with ubiquitous", "of erk with ubiquitous expression.


              " ] }, { "record_id": "GLY_000594_1_1047", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654704", "r hsa", "hsa 5654704", "r hsa 5654704" ] }, { "record_id": "GLY_000594_1_1047", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc mediated", "mediated cascade:fgfr3", "shc mediated cascade:fgfr3", "the exact", "exact role", "role of", "of shc1", "shc1 in", "in fgfr", "fgfr signaling", "signaling remains", "remains unclear.", "numerous studies", "studies have", "have shown", "shown that", "that the", "the p46", "p46 and", "and p52", "p52 isoforms", "isoforms of", "shc1 are", "are phosphorylated", "phosphorylated in", "in response", "response to", "to fgf", "fgf stimulation", "but direct", "direct interaction", "interaction with", "with the", "the receptor", "receptor has", "has not", "not been", "been demonstrated.", "demonstrated. co", "co precipitation", "precipitation of", "of p46", "p52 with", "the fgfr2", "fgfr2 iiic", "iiic receptor", "has been", "been reported", "but this", "this interaction", "interaction is", "is thought", "thought to", "to be", "be indirect", "possibly mediated", "mediated by", "by src.", "consistent with", "with this", "shc1 and", "and fgfr1", "fgfr1 iiic", "iiic is", "is seen", "seen in", "in mammalian", "mammalian cells", "cells expressing", "expressing v", "v src.", "the p66", "p66 isoform", "isoform of", "shc1 has", "has also", "also been", "been co", "co precipitated", "precipitated with", "with fgfr3", "this occurs", "occurs independently", "independently of", "of receptor", "receptor stimulation", "and the", "isoform not", "been shown", "shown to", "to undergo", "undergo fgf", "fgf dependent", "dependent phosphorylation.", "to associate", "associate with", "with grb2", "grb2 and", "and sos1", "sos1 in", "suggesting that", "the recruitment", "recruitment of", "shc1 may", "may contribute", "contribute to", "to activation", "activation of", "of the", "the mapk", "mapk cascade", "cascade downstream", "downstream of", "of fgfr.", "the exact role", "exact role of", "role of shc1", "of shc1 in", "shc1 in fgfr", "in fgfr signaling", "fgfr signaling remains", "signaling remains unclear.", "numerous studies have", "studies have shown", "have shown that", "shown that the", "that the p46", "the p46 and", "p46 and p52", "and p52 isoforms", "p52 isoforms of", "isoforms of shc1", "of shc1 are", "shc1 are phosphorylated", "are phosphorylated in", "phosphorylated in response", "in response to", "response to fgf", "to fgf stimulation", "stimulation but", "but direct interaction", "direct interaction with", "interaction with the", "with the receptor", "the receptor has", "receptor has not", "has not been", "not been demonstrated.", "been demonstrated. co", "demonstrated. co precipitation", "co precipitation of", "precipitation of p46", "of p46 and", "and p52 with", "p52 with the", "with the fgfr2", "the fgfr2 iiic", "fgfr2 iiic receptor", "iiic receptor has", "receptor has been", "has been reported", "reported but", "but this interaction", "this interaction is", "interaction is thought", "is thought to", "thought to be", "to be indirect", "indirect possibly", "possibly mediated by", "mediated by src.", "src. consistent", "consistent with this", "this co", "precipitation of shc1", "of shc1 and", "shc1 and fgfr1", "and fgfr1 iiic", "fgfr1 iiic is", "iiic is seen", "is seen in", "seen in mammalian", "in mammalian cells", "mammalian cells expressing", "cells expressing v", "expressing v src.", "src. the", "the p66 isoform", "p66 isoform of", "isoform of shc1", "of shc1 has", "shc1 has also", "has also been", "also been co", "been co precipitated", "co precipitated with", "precipitated with fgfr3", "fgfr3 but", "but this occurs", "this occurs independently", "occurs independently of", "independently of receptor", "of receptor stimulation", "stimulation and", "and the p66", "p66 isoform not", "isoform not been", "not been shown", "been shown to", "shown to undergo", "to undergo fgf", "undergo fgf dependent", "fgf dependent phosphorylation.", "phosphorylation. shc1", "shc1 has been", "has been shown", "shown to associate", "to associate with", "associate with grb2", "with grb2 and", "grb2 and sos1", "and sos1 in", "sos1 in response", "stimulation suggesting", "suggesting that the", "that the recruitment", "the recruitment of", "recruitment of shc1", "of shc1 may", "shc1 may contribute", "may contribute to", "contribute to activation", "to activation of", "activation of the", "of the mapk", "the mapk cascade", "mapk cascade downstream", "cascade downstream of", "downstream of fgfr.", "the exact role of", "exact role of shc1", "role of shc1 in", "of shc1 in fgfr", "shc1 in fgfr signaling", "in fgfr signaling remains", "fgfr signaling remains unclear.", "unclear. numerous", "numerous studies have shown", "studies have shown that", "have shown that the", "shown that the p46", "that the p46 and", "the p46 and p52", "p46 and p52 isoforms", "and p52 isoforms of", "p52 isoforms of shc1", "isoforms of shc1 are", "of shc1 are phosphorylated", "shc1 are phosphorylated in", "are phosphorylated in response", "phosphorylated in response to", "in response to fgf", "response to fgf stimulation", "fgf stimulation but", "stimulation but direct", "but direct interaction with", "direct interaction with the", "interaction with the receptor", "with the receptor has", "the receptor has not", "receptor has not been", "has not been demonstrated.", "not been demonstrated. co", "been demonstrated. co precipitation", "demonstrated. co precipitation of", "co precipitation of p46", "precipitation of p46 and", "of p46 and p52", "p46 and p52 with", "and p52 with the", "p52 with the fgfr2", "with the fgfr2 iiic", "the fgfr2 iiic receptor", "fgfr2 iiic receptor has", "iiic receptor has been", "receptor has been reported", "been reported but", "reported but this", "but this interaction is", "this interaction is thought", "interaction is thought to", "is thought to be", "thought to be indirect", "be indirect possibly", "indirect possibly mediated", "possibly mediated by src.", "by src. consistent", "src. consistent with", "with this co", "this co precipitation", "co precipitation of shc1", "precipitation of shc1 and", "of shc1 and fgfr1", "shc1 and fgfr1 iiic", "and fgfr1 iiic is", "fgfr1 iiic is seen", "iiic is seen in", "is seen in mammalian", "seen in mammalian cells", "in mammalian cells expressing", "mammalian cells expressing v", "cells expressing v src.", "v src. the", "src. the p66", "the p66 isoform of", "p66 isoform of shc1", "isoform of shc1 has", "of shc1 has also", "shc1 has also been", "has also been co", "also been co precipitated", "been co precipitated with", "co precipitated with fgfr3", "with fgfr3 but", "fgfr3 but this", "but this occurs independently", "this occurs independently of", "occurs independently of receptor", "independently of receptor stimulation", "receptor stimulation and", "stimulation and the", "and the p66 isoform", "the p66 isoform not", "p66 isoform not been", "isoform not been shown", "not been shown to", "been shown to undergo", "shown to undergo fgf", "to undergo fgf dependent", "undergo fgf dependent phosphorylation.", "dependent phosphorylation. shc1", "phosphorylation. shc1 has", "shc1 has been shown", "has been shown to", "been shown to associate", "shown to associate with", "to associate with grb2", "associate with grb2 and", "with grb2 and sos1", "grb2 and sos1 in", "and sos1 in response", "sos1 in response to", "fgf stimulation suggesting", "stimulation suggesting that", "suggesting that the recruitment", "that the recruitment of", "the recruitment of shc1", "recruitment of shc1 may", "of shc1 may contribute", "shc1 may contribute to", "may contribute to activation", "contribute to activation of", "to activation of the", "activation of the mapk", "of the mapk cascade", "the mapk cascade downstream", "mapk cascade downstream of", "cascade downstream of fgfr.", "the exact role of shc1", "exact role of shc1 in", "role of shc1 in fgfr", "of shc1 in fgfr signaling", "shc1 in fgfr signaling remains", "in fgfr signaling remains unclear.", "remains unclear. numerous", "unclear. numerous studies", "numerous studies have shown that", "studies have shown that the", "have shown that the p46", "shown that the p46 and", "that the p46 and p52", "the p46 and p52 isoforms", "p46 and p52 isoforms of", "and p52 isoforms of shc1", "p52 isoforms of shc1 are", "isoforms of shc1 are phosphorylated", "of shc1 are phosphorylated in", "shc1 are phosphorylated in response", "are phosphorylated in response to", "phosphorylated in response to fgf", "in response to fgf stimulation", "to fgf stimulation but", "fgf stimulation but direct", "stimulation but direct interaction", "but direct interaction with the", "direct interaction with the receptor", "interaction with the receptor has", "with the receptor has not", "the receptor has not been", "receptor has not been demonstrated.", "has not been demonstrated. co", "not been demonstrated. co precipitation", "been demonstrated. co precipitation of", "demonstrated. co precipitation of p46", "co precipitation of p46 and", "precipitation of p46 and p52", "of p46 and p52 with", "p46 and p52 with the", "and p52 with the fgfr2", "p52 with the fgfr2 iiic", "with the fgfr2 iiic receptor", "the fgfr2 iiic receptor has", "fgfr2 iiic receptor has been", "iiic receptor has been reported", "has been reported but", "been reported but this", "reported but this interaction", "but this interaction is thought", "this interaction is thought to", "interaction is thought to be", "is thought to be indirect", "to be indirect possibly", "be indirect possibly mediated", "indirect possibly mediated by", "mediated by src. consistent", "by src. consistent with", "src. consistent with this", "consistent with this co", "with this co precipitation", "this co precipitation of", "co precipitation of shc1 and", "precipitation of shc1 and fgfr1", "of shc1 and fgfr1 iiic", "shc1 and fgfr1 iiic is", "and fgfr1 iiic is seen", "fgfr1 iiic is seen in", "iiic is seen in mammalian", "is seen in mammalian cells", "seen in mammalian cells expressing", "in mammalian cells expressing v", "mammalian cells expressing v src.", "expressing v src. the", "v src. the p66", "src. the p66 isoform", "the p66 isoform of shc1", "p66 isoform of shc1 has", "isoform of shc1 has also", "of shc1 has also been", "shc1 has also been co", "has also been co precipitated", "also been co precipitated with", "been co precipitated with fgfr3", "precipitated with fgfr3 but", "with fgfr3 but this", "fgfr3 but this occurs", "but this occurs independently of", "this occurs independently of receptor", "occurs independently of receptor stimulation", "of receptor stimulation and", "receptor stimulation and the", "stimulation and the p66", "and the p66 isoform not", "the p66 isoform not been", "p66 isoform not been shown", "isoform not been shown to", "not been shown to undergo", "been shown to undergo fgf", "shown to undergo fgf dependent", "to undergo fgf dependent phosphorylation.", "fgf dependent phosphorylation. shc1", "dependent phosphorylation. shc1 has", "phosphorylation. shc1 has been", "shc1 has been shown to", "has been shown to associate", "been shown to associate with", "shown to associate with grb2", "to associate with grb2 and", "associate with grb2 and sos1", "with grb2 and sos1 in", "grb2 and sos1 in response", "and sos1 in response to", "sos1 in response to fgf", "to fgf stimulation suggesting", "fgf stimulation suggesting that", "stimulation suggesting that the", "suggesting that the recruitment of", "that the recruitment of shc1", "the recruitment of shc1 may", "recruitment of shc1 may contribute", "of shc1 may contribute to", "shc1 may contribute to activation", "may contribute to activation of", "contribute to activation of the", "to activation of the mapk", "activation of the mapk cascade", "of the mapk cascade downstream", "the mapk cascade downstream of", "mapk cascade downstream of fgfr." ] }, { "record_id": "GLY_000594_1_1048", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654706", "r hsa", "hsa 5654706", "r hsa 5654706" ] }, { "record_id": "GLY_000594_1_1048", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "frs mediated", "mediated fgfr3", "fgfr3 signaling", "frs mediated fgfr3", "mediated fgfr3 signaling", "frs mediated fgfr3 signaling", "the frs", "frs family", "family of", "of scaffolding", "scaffolding adaptor", "adaptor proteins", "proteins has", "has two", "two members", "also known", "known as", "as frs2", "frs2 alpha", "and frs3", "as frs2beta", "frs2beta or", "or snt", "snt 2", "2 .", "activation of", "of fgfr", "fgfr tyrosine", "tyrosine kinase", "kinase allows", "allows frs", "frs proteins", "proteins to", "to become", "become phosphorylated", "phosphorylated on", "on tyrosine", "tyrosine residues", "residues and", "and then", "then bind", "bind to", "to the", "the adaptor", "adaptor grb2", "grb2 and", "and the", "the tyrosine", "tyrosine phosphatase", "phosphatase pptn11/shp2.", "pptn11 activates", "activates the", "the ras", "ras map", "map kinase", "kinase pathway", "pathway and", "and grb2", "grb2 activates", "pi 3", "3 kinase", "kinase and", "and ubiquitinations/degradation", "ubiquitinations/degradation pathways", "pathways by", "by binding", "binding to", "to sos", "gab1 and", "and cbl", "via the", "the sh3", "sh3 domains", "domains of", "of grb2.", "frs2 acts", "acts as", "as a", "a central", "central mediator", "mediator in", "in fgf", "fgf signaling", "signaling mainly", "mainly because", "because it", "it induces", "induces sustained", "sustained levels", "levels of", "of activation", "of erk", "erk with", "with ubiquitous", "ubiquitous expression.


              ", "the frs family", "frs family of", "family of scaffolding", "of scaffolding adaptor", "scaffolding adaptor proteins", "adaptor proteins has", "proteins has two", "has two members", "members frs2", "frs2 also", "also known as", "known as frs2", "as frs2 alpha", "alpha and", "frs3 also", "known as frs2beta", "as frs2beta or", "frs2beta or snt", "or snt 2", "snt 2 .", ". activation", "activation of fgfr", "of fgfr tyrosine", "fgfr tyrosine kinase", "tyrosine kinase allows", "kinase allows frs", "allows frs proteins", "frs proteins to", "proteins to become", "to become phosphorylated", "become phosphorylated on", "phosphorylated on tyrosine", "on tyrosine residues", "tyrosine residues and", "residues and then", "and then bind", "then bind to", "bind to the", "to the adaptor", "the adaptor grb2", "adaptor grb2 and", "grb2 and the", "and the tyrosine", "the tyrosine phosphatase", "tyrosine phosphatase pptn11/shp2.", "pptn11/shp2. subsequently", "subsequently pptn11", "pptn11 activates the", "activates the ras", "the ras map", "ras map kinase", "map kinase pathway", "kinase pathway and", "pathway and grb2", "and grb2 activates", "grb2 activates the", "pi 3 kinase", "3 kinase and", "kinase and ubiquitinations/degradation", "and ubiquitinations/degradation pathways", "ubiquitinations/degradation pathways by", "pathways by binding", "by binding to", "binding to sos", "sos gab1", "gab1 and cbl", "cbl respectively", "respectively via", "via the sh3", "the sh3 domains", "sh3 domains of", "domains of grb2.", "grb2. frs2", "frs2 acts as", "acts as a", "as a central", "a central mediator", "central mediator in", "mediator in fgf", "in fgf signaling", "fgf signaling mainly", "signaling mainly because", "mainly because it", "because it induces", "it induces sustained", "induces sustained levels", "sustained levels of", "levels of activation", "of activation of", "activation of erk", "of erk with", "erk with ubiquitous", "with ubiquitous expression.


              ", "the frs family of", "frs family of scaffolding", "family of scaffolding adaptor", "of scaffolding adaptor proteins", "scaffolding adaptor proteins has", "adaptor proteins has two", "proteins has two members", "two members frs2", "frs2 also known", "also known as frs2", "known as frs2 alpha", "frs2 alpha and", "alpha and frs3", "and frs3 also", "frs3 also known", "also known as frs2beta", "known as frs2beta or", "as frs2beta or snt", "frs2beta or snt 2", "or snt 2 .", "2 . activation", ". activation of", "activation of fgfr tyrosine", "of fgfr tyrosine kinase", "fgfr tyrosine kinase allows", "tyrosine kinase allows frs", "kinase allows frs proteins", "allows frs proteins to", "frs proteins to become", "proteins to become phosphorylated", "to become phosphorylated on", "become phosphorylated on tyrosine", "phosphorylated on tyrosine residues", "on tyrosine residues and", "tyrosine residues and then", "residues and then bind", "and then bind to", "then bind to the", "bind to the adaptor", "to the adaptor grb2", "the adaptor grb2 and", "adaptor grb2 and the", "grb2 and the tyrosine", "and the tyrosine phosphatase", "the tyrosine phosphatase pptn11/shp2.", "phosphatase pptn11/shp2. subsequently", "subsequently pptn11 activates", "pptn11 activates the ras", "activates the ras map", "the ras map kinase", "ras map kinase pathway", "map kinase pathway and", "kinase pathway and grb2", "pathway and grb2 activates", "and grb2 activates the", "grb2 activates the ras", "kinase pi", "pi 3 kinase and", "3 kinase and ubiquitinations/degradation", "kinase and ubiquitinations/degradation pathways", "and ubiquitinations/degradation pathways by", "ubiquitinations/degradation pathways by binding", "pathways by binding to", "by binding to sos", "to sos gab1", "sos gab1 and", "and cbl respectively", "respectively via the", "via the sh3 domains", "the sh3 domains of", "sh3 domains of grb2.", "of grb2. frs2", "grb2. frs2 acts", "frs2 acts as a", "acts as a central", "as a central mediator", "a central mediator in", "central mediator in fgf", "mediator in fgf signaling", "in fgf signaling mainly", "fgf signaling mainly because", "signaling mainly because it", "mainly because it induces", "because it induces sustained", "it induces sustained levels", "induces sustained levels of", "sustained levels of activation", "levels of activation of", "of activation of erk", "activation of erk with", "of erk with ubiquitous", "erk with ubiquitous expression.


              ", "the frs family of scaffolding", "frs family of scaffolding adaptor", "family of scaffolding adaptor proteins", "of scaffolding adaptor proteins has", "scaffolding adaptor proteins has two", "adaptor proteins has two members", "has two members frs2", "members frs2 also", "frs2 also known as", "also known as frs2 alpha", "as frs2 alpha and", "frs2 alpha and frs3", "and frs3 also known", "frs3 also known as", "also known as frs2beta or", "known as frs2beta or snt", "as frs2beta or snt 2", "frs2beta or snt 2 .", "snt 2 . activation", "2 . activation of", ". activation of fgfr", "activation of fgfr tyrosine kinase", "of fgfr tyrosine kinase allows", "fgfr tyrosine kinase allows frs", "tyrosine kinase allows frs proteins", "kinase allows frs proteins to", "allows frs proteins to become", "frs proteins to become phosphorylated", "proteins to become phosphorylated on", "to become phosphorylated on tyrosine", "become phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues and", "on tyrosine residues and then", "tyrosine residues and then bind", "residues and then bind to", "and then bind to the", "then bind to the adaptor", "bind to the adaptor grb2", "to the adaptor grb2 and", "the adaptor grb2 and the", "adaptor grb2 and the tyrosine", "grb2 and the tyrosine phosphatase", "and the tyrosine phosphatase pptn11/shp2.", "tyrosine phosphatase pptn11/shp2. subsequently", "pptn11/shp2. subsequently pptn11", "subsequently pptn11 activates the", "pptn11 activates the ras map", "activates the ras map kinase", "the ras map kinase pathway", "ras map kinase pathway and", "map kinase pathway and grb2", "kinase pathway and grb2 activates", "pathway and grb2 activates the", "and grb2 activates the ras", "grb2 activates the ras map", "map kinase pi", "kinase pi 3", "pi 3 kinase and ubiquitinations/degradation", "3 kinase and ubiquitinations/degradation pathways", "kinase and ubiquitinations/degradation pathways by", "and ubiquitinations/degradation pathways by binding", "ubiquitinations/degradation pathways by binding to", "pathways by binding to sos", "binding to sos gab1", "to sos gab1 and", "sos gab1 and cbl", "gab1 and cbl respectively", "cbl respectively via", "respectively via the sh3", "via the sh3 domains of", "the sh3 domains of grb2.", "domains of grb2. frs2", "of grb2. frs2 acts", "grb2. frs2 acts as", "frs2 acts as a central", "acts as a central mediator", "as a central mediator in", "a central mediator in fgf", "central mediator in fgf signaling", "mediator in fgf signaling mainly", "in fgf signaling mainly because", "fgf signaling mainly because it", "signaling mainly because it induces", "mainly because it induces sustained", "because it induces sustained levels", "it induces sustained levels of", "induces sustained levels of activation", "sustained levels of activation of", "levels of activation of erk", "of activation of erk with", "activation of erk with ubiquitous", "of erk with ubiquitous expression.


              " ] }, { "record_id": "GLY_000594_1_1049", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654710", "r hsa", "hsa 5654710", "r hsa 5654710" ] }, { "record_id": "GLY_000594_1_1049", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi 3k", "3k cascade:fgfr3", "pi 3k cascade:fgfr3", "the ability", "ability of", "of growth", "growth factors", "factors to", "to protect", "protect from", "from apoptosis", "apoptosis is", "is primarily", "primarily due", "due to", "to the", "the activation", "activation of", "of the", "the akt", "akt survival", "survival pathway.", "pathway. p", "p i", "i 3", "3 kinase", "kinase dependent", "dependent activation", "of pdk", "pdk leads", "leads to", "of akt", "akt which", "which in", "in turn", "turn affects", "affects the", "the activity", "activity or", "or expression", "expression of", "of pro", "pro apoptotic", "apoptotic factors", "which contribute", "contribute to", "to protection", "protection from", "from apoptosis.", "apoptosis. akt", "akt activation", "activation also", "also blocks", "blocks the", "activity of", "of gsk", "gsk 3b", "3b which", "which could", "could lead", "lead to", "to additional", "additional antiapoptotic", "antiapoptotic signals.", "the ability of", "ability of growth", "of growth factors", "growth factors to", "factors to protect", "to protect from", "protect from apoptosis", "from apoptosis is", "apoptosis is primarily", "is primarily due", "primarily due to", "due to the", "to the activation", "the activation of", "activation of the", "of the akt", "the akt survival", "akt survival pathway.", "survival pathway. p", "pathway. p i", "p i 3", "i 3 kinase", "3 kinase dependent", "kinase dependent activation", "dependent activation of", "activation of pdk", "of pdk leads", "pdk leads to", "leads to the", "activation of akt", "of akt which", "akt which in", "which in turn", "in turn affects", "turn affects the", "affects the activity", "the activity or", "activity or expression", "or expression of", "expression of pro", "of pro apoptotic", "pro apoptotic factors", "factors which", "which contribute to", "contribute to protection", "to protection from", "protection from apoptosis.", "from apoptosis. akt", "apoptosis. akt activation", "akt activation also", "activation also blocks", "also blocks the", "blocks the activity", "the activity of", "activity of gsk", "of gsk 3b", "gsk 3b which", "3b which could", "which could lead", "could lead to", "lead to additional", "to additional antiapoptotic", "additional antiapoptotic signals.", "the ability of growth", "ability of growth factors", "of growth factors to", "growth factors to protect", "factors to protect from", "to protect from apoptosis", "protect from apoptosis is", "from apoptosis is primarily", "apoptosis is primarily due", "is primarily due to", "primarily due to the", "due to the activation", "to the activation of", "the activation of the", "activation of the akt", "of the akt survival", "the akt survival pathway.", "akt survival pathway. p", "survival pathway. p i", "pathway. p i 3", "p i 3 kinase", "i 3 kinase dependent", "3 kinase dependent activation", "kinase dependent activation of", "dependent activation of pdk", "activation of pdk leads", "of pdk leads to", "pdk leads to the", "leads to the activation", "the activation of akt", "activation of akt which", "of akt which in", "akt which in turn", "which in turn affects", "in turn affects the", "turn affects the activity", "affects the activity or", "the activity or expression", "activity or expression of", "or expression of pro", "expression of pro apoptotic", "of pro apoptotic factors", "apoptotic factors which", "factors which contribute", "which contribute to protection", "contribute to protection from", "to protection from apoptosis.", "protection from apoptosis. akt", "from apoptosis. akt activation", "apoptosis. akt activation also", "akt activation 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kinase dependent activation", "3 kinase dependent activation of", "kinase dependent activation of pdk", "dependent activation of pdk leads", "activation of pdk leads to", "of pdk leads to the", "pdk leads to the activation", "leads to the activation of", "to the activation of akt", "the activation of akt which", "activation of akt which in", "of akt which in turn", "akt which in turn affects", "which in turn affects the", "in turn affects the activity", "turn affects the activity or", "affects the activity or expression", "the activity or expression of", "activity or expression of pro", "or expression of pro apoptotic", "expression of pro apoptotic factors", "pro apoptotic factors which", "apoptotic factors which contribute", "factors which contribute to", "which contribute to protection from", "contribute to protection from apoptosis.", "to protection from apoptosis. akt", "protection from apoptosis. akt activation", "from apoptosis. akt activation also", "apoptosis. akt activation also blocks", "akt activation also blocks the", "activation also blocks the activity", "also blocks the activity of", "blocks the activity of gsk", "the activity of gsk 3b", "activity of gsk 3b which", "of gsk 3b which could", "gsk 3b which could lead", "3b which could lead to", "which could lead to additional", "could lead to additional antiapoptotic", "lead to additional antiapoptotic signals." ] }, { "record_id": "GLY_000594_1_1050", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654712", "r hsa", "hsa 5654712", "r hsa 5654712" ] }, { "record_id": "GLY_000594_1_1050", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "frs mediated", "mediated fgfr4", "fgfr4 signaling", "frs mediated fgfr4", "mediated fgfr4 signaling", "frs mediated fgfr4 signaling", "the frs", "frs family", "family of", "of scaffolding", "scaffolding adaptor", "adaptor proteins", "proteins has", "has two", "two members", "also known", "known as", "as frs2", "frs2 alpha", "and frs3", "as frs2beta", "frs2beta or", "or snt", "snt 2", "2 .", "activation of", "of fgfr", "fgfr tyrosine", "tyrosine kinase", "kinase allows", "allows frs", "frs proteins", "proteins to", "to become", "become phosphorylated", "phosphorylated on", "on tyrosine", "tyrosine residues", "residues and", "and then", "then bind", "bind to", "to the", "the adaptor", "adaptor grb2", "grb2 and", "and the", "the tyrosine", "tyrosine phosphatase", "phosphatase pptn11/shp2.", "pptn11 activates", "activates the", "the ras", "ras map", "map kinase", "kinase pathway", "pathway and", "and grb2", "grb2 activates", "pi 3", "3 kinase", "kinase and", "and ubiquitinations/degradation", "ubiquitinations/degradation pathways", "pathways by", "by binding", "binding to", "to sos", "gab1 and", "and cbl", "via the", "the sh3", "sh3 domains", "domains of", "of grb2.", "frs2 acts", "acts as", "as a", "a central", "central mediator", "mediator in", "in fgf", "fgf signaling", "signaling mainly", "mainly because", "because it", "it induces", "induces sustained", "sustained levels", "levels of", "of activation", "of erk", "erk with", "with ubiquitous", "ubiquitous expression.


              ", "the frs family", "frs family of", "family of scaffolding", "of scaffolding adaptor", "scaffolding adaptor proteins", "adaptor proteins has", "proteins has two", "has two members", "members frs2", "frs2 also", "also known as", "known as frs2", "as frs2 alpha", "alpha and", "frs3 also", "known as frs2beta", "as frs2beta or", "frs2beta or snt", "or snt 2", "snt 2 .", ". activation", "activation of fgfr", "of fgfr tyrosine", "fgfr tyrosine kinase", "tyrosine kinase allows", "kinase allows frs", "allows frs proteins", "frs proteins to", "proteins to become", "to become phosphorylated", "become phosphorylated on", "phosphorylated on tyrosine", "on tyrosine residues", "tyrosine residues and", "residues and then", "and then bind", "then bind to", "bind to the", "to the adaptor", "the adaptor grb2", "adaptor grb2 and", "grb2 and the", "and the tyrosine", "the tyrosine phosphatase", "tyrosine phosphatase pptn11/shp2.", "pptn11/shp2. subsequently", "subsequently pptn11", "pptn11 activates the", "activates the ras", "the ras map", "ras map kinase", "map kinase pathway", "kinase pathway and", "pathway and grb2", "and grb2 activates", "grb2 activates the", "pi 3 kinase", "3 kinase and", "kinase and ubiquitinations/degradation", "and ubiquitinations/degradation pathways", "ubiquitinations/degradation pathways by", "pathways by binding", "by binding to", "binding to sos", "sos gab1", "gab1 and cbl", "cbl respectively", "respectively via", "via the sh3", "the sh3 domains", "sh3 domains of", "domains of grb2.", "grb2. frs2", "frs2 acts as", "acts as a", "as a central", "a central mediator", "central mediator in", "mediator in fgf", "in fgf signaling", "fgf signaling mainly", "signaling mainly because", "mainly because it", "because it induces", "it induces sustained", "induces sustained levels", "sustained levels of", "levels of activation", "of activation of", "activation of erk", "of erk with", "erk with ubiquitous", "with ubiquitous expression.


              ", "the frs family of", "frs family of scaffolding", "family of scaffolding adaptor", "of scaffolding adaptor proteins", "scaffolding adaptor proteins has", "adaptor proteins has two", "proteins has two members", "two members frs2", "frs2 also known", "also known as frs2", "known as frs2 alpha", "frs2 alpha and", "alpha and frs3", "and frs3 also", "frs3 also known", "also known as frs2beta", "known as frs2beta or", "as frs2beta or snt", "frs2beta or snt 2", "or snt 2 .", "2 . activation", ". activation of", "activation of fgfr tyrosine", "of fgfr tyrosine kinase", "fgfr tyrosine kinase allows", "tyrosine kinase allows frs", "kinase allows frs proteins", "allows frs proteins to", "frs proteins to become", "proteins to become phosphorylated", "to become phosphorylated on", "become phosphorylated on tyrosine", "phosphorylated on tyrosine residues", "on tyrosine residues and", "tyrosine residues and then", "residues and then bind", "and then bind to", "then bind to the", "bind to the adaptor", "to the adaptor grb2", "the adaptor grb2 and", "adaptor grb2 and the", "grb2 and the tyrosine", "and the tyrosine phosphatase", "the tyrosine phosphatase pptn11/shp2.", "phosphatase pptn11/shp2. subsequently", "subsequently pptn11 activates", "pptn11 activates the ras", "activates the ras map", "the ras map kinase", "ras map kinase pathway", "map kinase pathway and", "kinase pathway and grb2", "pathway and grb2 activates", "and grb2 activates the", "grb2 activates the ras", "kinase pi", "pi 3 kinase and", "3 kinase and ubiquitinations/degradation", "kinase and ubiquitinations/degradation pathways", "and ubiquitinations/degradation pathways by", "ubiquitinations/degradation pathways by binding", "pathways by binding to", "by binding to sos", "to sos gab1", "sos gab1 and", "and cbl respectively", "respectively via the", "via the sh3 domains", "the sh3 domains of", "sh3 domains of grb2.", "of grb2. frs2", "grb2. frs2 acts", "frs2 acts as a", "acts as a central", "as a central mediator", "a central mediator in", "central mediator in fgf", "mediator in fgf signaling", "in fgf signaling mainly", "fgf signaling mainly because", "signaling mainly because it", "mainly because it induces", "because it induces sustained", "it induces sustained levels", "induces sustained levels of", "sustained levels of activation", "levels of activation of", "of activation of erk", "activation of erk with", "of erk with ubiquitous", "erk with ubiquitous expression.


              ", "the frs family of scaffolding", "frs family of scaffolding adaptor", "family of scaffolding adaptor proteins", "of scaffolding adaptor proteins has", "scaffolding adaptor proteins has two", "adaptor proteins has two members", "has two members frs2", "members frs2 also", "frs2 also known as", "also known as frs2 alpha", "as frs2 alpha and", "frs2 alpha and frs3", "and frs3 also known", "frs3 also known as", "also known as frs2beta or", "known as frs2beta or snt", "as frs2beta or snt 2", "frs2beta or snt 2 .", "snt 2 . activation", "2 . activation of", ". activation of fgfr", "activation of fgfr tyrosine kinase", "of fgfr tyrosine kinase allows", "fgfr tyrosine kinase allows frs", "tyrosine kinase allows frs proteins", "kinase allows frs proteins to", "allows frs proteins to become", "frs proteins to become phosphorylated", "proteins to become phosphorylated on", "to become phosphorylated on tyrosine", "become phosphorylated on tyrosine residues", "phosphorylated on tyrosine residues and", "on tyrosine residues and then", "tyrosine residues and then bind", "residues and then bind to", "and then bind to the", "then bind to the adaptor", "bind to the adaptor grb2", "to the adaptor grb2 and", "the adaptor grb2 and the", "adaptor grb2 and the tyrosine", "grb2 and the tyrosine phosphatase", "and the tyrosine phosphatase pptn11/shp2.", "tyrosine phosphatase pptn11/shp2. subsequently", "pptn11/shp2. subsequently pptn11", "subsequently pptn11 activates the", "pptn11 activates the ras map", "activates the ras map kinase", "the ras map kinase pathway", "ras map kinase pathway and", "map kinase pathway and grb2", "kinase pathway and grb2 activates", "pathway and grb2 activates the", "and grb2 activates the ras", "grb2 activates the ras map", "map kinase pi", "kinase pi 3", "pi 3 kinase and ubiquitinations/degradation", "3 kinase and ubiquitinations/degradation pathways", "kinase and ubiquitinations/degradation pathways by", "and ubiquitinations/degradation pathways by binding", "ubiquitinations/degradation pathways by binding to", "pathways by binding to sos", "binding to sos gab1", "to sos gab1 and", "sos gab1 and cbl", "gab1 and cbl respectively", "cbl respectively via", "respectively via the sh3", "via the sh3 domains of", "the sh3 domains of grb2.", "domains of grb2. frs2", "of grb2. frs2 acts", "grb2. frs2 acts as", "frs2 acts as a central", "acts as a central mediator", "as a central mediator in", "a central mediator in fgf", "central mediator in fgf signaling", "mediator in fgf signaling mainly", "in fgf signaling mainly because", "fgf signaling mainly because it", "signaling mainly because it induces", "mainly because it induces sustained", "because it induces sustained levels", "it induces sustained levels of", "induces sustained levels of activation", "sustained levels of activation of", "levels of activation of erk", "of activation of erk with", "activation of erk with ubiquitous", "of erk with ubiquitous expression.


              " ] }, { "record_id": "GLY_000594_1_1051", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654719", "r hsa", "hsa 5654719", "r hsa 5654719" ] }, { "record_id": "GLY_000594_1_1051", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "shc mediated", "mediated cascade:fgfr4", "shc mediated cascade:fgfr4", "the exact", "exact role", "role of", "of shc1", "shc1 in", "in fgfr", "fgfr signaling", "signaling remains", "remains unclear.", "numerous studies", "studies have", "have shown", "shown that", "that the", "the p46", "p46 and", "and p52", "p52 isoforms", "isoforms of", "shc1 are", "are phosphorylated", "phosphorylated in", "in response", "response to", "to fgf", "fgf stimulation", "but direct", "direct interaction", "interaction with", "with the", "the receptor", "receptor has", "has not", "not been", "been demonstrated.", "demonstrated. co", "co precipitation", "precipitation of", "of p46", "p52 with", "the fgfr2", "fgfr2 iiic", "iiic receptor", "has been", "been reported", "but this", "this interaction", "interaction is", "is thought", "thought to", "to be", "be indirect", "possibly mediated", "mediated by", "by src.", "consistent with", "with this", "shc1 and", "and fgfr1", "fgfr1 iiic", "iiic is", "is seen", "seen in", "in mammalian", "mammalian cells", "cells expressing", "expressing v", "v src.", "the p66", "p66 isoform", "isoform of", "shc1 has", "has also", "also been", "been co", "co precipitated", "precipitated with", "with fgfr3", "this occurs", "occurs independently", "independently of", "of receptor", "receptor stimulation", "and the", "isoform not", "been shown", "shown to", "to undergo", "undergo fgf", "fgf dependent", "dependent phosphorylation.", "to associate", "associate with", "with grb2", "grb2 and", "and sos1", "sos1 in", "suggesting that", "the recruitment", "recruitment of", "shc1 may", "may contribute", "contribute to", "to activation", "activation of", "of the", "the mapk", "mapk cascade", "cascade downstream", "downstream of", "of fgfr.", "the exact role", "exact role of", "role of shc1", "of shc1 in", "shc1 in fgfr", "in fgfr signaling", "fgfr signaling remains", "signaling remains unclear.", "numerous studies have", "studies have shown", "have shown that", "shown that the", "that the p46", "the p46 and", "p46 and p52", "and p52 isoforms", "p52 isoforms of", "isoforms of shc1", "of shc1 are", "shc1 are phosphorylated", "are phosphorylated in", "phosphorylated in response", "in response to", "response to fgf", "to fgf stimulation", "stimulation but", "but direct interaction", "direct interaction with", "interaction with the", "with the receptor", "the receptor has", "receptor has not", "has not been", "not been demonstrated.", "been demonstrated. co", "demonstrated. co precipitation", "co precipitation of", "precipitation of p46", "of p46 and", "and p52 with", "p52 with the", "with the fgfr2", "the fgfr2 iiic", "fgfr2 iiic receptor", "iiic receptor has", "receptor has been", "has been reported", "reported but", "but this interaction", "this interaction is", "interaction is thought", "is thought to", "thought to be", "to be indirect", "indirect possibly", "possibly mediated by", "mediated by src.", "src. consistent", "consistent with this", "this co", "precipitation of shc1", "of shc1 and", "shc1 and fgfr1", "and fgfr1 iiic", "fgfr1 iiic is", "iiic is seen", "is seen in", "seen in mammalian", "in mammalian cells", "mammalian cells expressing", "cells expressing v", "expressing v src.", "src. the", "the p66 isoform", "p66 isoform of", "isoform of shc1", "of shc1 has", "shc1 has also", "has also been", "also been co", "been co precipitated", "co precipitated with", "precipitated with fgfr3", "fgfr3 but", "but this occurs", "this occurs independently", "occurs independently of", "independently of receptor", "of receptor stimulation", "stimulation and", "and the p66", "p66 isoform not", "isoform not been", "not been shown", "been shown to", "shown to undergo", "to undergo fgf", "undergo fgf dependent", "fgf dependent phosphorylation.", "phosphorylation. shc1", "shc1 has been", "has been shown", "shown to associate", "to associate with", "associate with grb2", "with grb2 and", "grb2 and sos1", "and sos1 in", "sos1 in response", "stimulation suggesting", "suggesting that the", "that the recruitment", "the recruitment of", "recruitment of shc1", "of shc1 may", "shc1 may contribute", "may contribute to", "contribute to activation", "to activation of", "activation of the", "of the mapk", "the mapk cascade", "mapk cascade downstream", "cascade downstream of", "downstream of fgfr.", "the exact role of", "exact role of shc1", "role of shc1 in", "of shc1 in fgfr", "shc1 in fgfr signaling", "in fgfr signaling remains", "fgfr signaling remains unclear.", "unclear. numerous", "numerous studies have shown", "studies have shown that", "have shown that the", "shown that the p46", "that the p46 and", "the p46 and p52", "p46 and p52 isoforms", "and p52 isoforms of", "p52 isoforms of shc1", "isoforms of shc1 are", "of shc1 are phosphorylated", "shc1 are phosphorylated in", "are phosphorylated in response", "phosphorylated in response to", "in response to fgf", "response to fgf stimulation", "fgf stimulation but", "stimulation but direct", "but direct interaction with", "direct interaction with the", "interaction with the receptor", "with the receptor has", "the receptor has not", "receptor has not been", "has not been demonstrated.", "not been demonstrated. co", "been demonstrated. co precipitation", "demonstrated. co precipitation of", "co precipitation of p46", "precipitation of p46 and", "of p46 and p52", "p46 and p52 with", "and p52 with the", "p52 with the fgfr2", "with the fgfr2 iiic", "the fgfr2 iiic receptor", "fgfr2 iiic receptor has", "iiic receptor has been", "receptor has been reported", "been reported but", "reported but this", "but this interaction is", "this interaction is thought", "interaction is thought to", "is thought to be", "thought to be indirect", "be indirect possibly", "indirect possibly mediated", "possibly mediated by src.", "by src. consistent", "src. consistent with", "with this co", "this co precipitation", "co precipitation of shc1", "precipitation of shc1 and", "of shc1 and fgfr1", "shc1 and fgfr1 iiic", "and fgfr1 iiic is", "fgfr1 iiic is seen", "iiic is seen in", "is seen in mammalian", "seen in mammalian cells", "in mammalian cells expressing", "mammalian cells expressing v", "cells expressing v src.", "v src. the", "src. the p66", "the p66 isoform of", "p66 isoform of shc1", "isoform of shc1 has", "of shc1 has also", "shc1 has also been", "has also been co", "also been co precipitated", "been co precipitated with", "co precipitated with fgfr3", "with fgfr3 but", "fgfr3 but this", "but this occurs independently", "this occurs independently of", "occurs independently of receptor", "independently of receptor stimulation", "receptor stimulation and", "stimulation and the", "and the p66 isoform", "the p66 isoform not", "p66 isoform not been", "isoform not been shown", "not been shown to", "been shown to undergo", "shown to undergo fgf", "to undergo fgf dependent", "undergo fgf dependent phosphorylation.", "dependent phosphorylation. shc1", "phosphorylation. shc1 has", "shc1 has been shown", "has been shown to", "been shown to associate", "shown to associate with", "to associate with grb2", "associate with grb2 and", "with grb2 and sos1", "grb2 and sos1 in", "and sos1 in response", "sos1 in response to", "fgf stimulation suggesting", "stimulation suggesting that", "suggesting that the recruitment", "that the recruitment of", "the recruitment of shc1", "recruitment of shc1 may", "of shc1 may contribute", "shc1 may contribute to", "may contribute to activation", "contribute to activation of", "to activation of the", "activation of the mapk", "of the mapk cascade", "the mapk cascade downstream", "mapk cascade downstream of", "cascade downstream of fgfr.", "the exact role of shc1", "exact role of shc1 in", "role of shc1 in fgfr", "of shc1 in fgfr signaling", "shc1 in fgfr signaling remains", "in fgfr signaling remains unclear.", "remains unclear. numerous", "unclear. numerous studies", "numerous studies have shown that", "studies have shown that the", "have shown that the p46", "shown that the p46 and", "that the p46 and p52", "the p46 and p52 isoforms", "p46 and p52 isoforms of", "and p52 isoforms of shc1", "p52 isoforms of shc1 are", "isoforms of shc1 are phosphorylated", "of shc1 are phosphorylated in", "shc1 are phosphorylated in response", "are phosphorylated in response to", "phosphorylated in response to fgf", "in response to fgf stimulation", "to fgf stimulation but", "fgf stimulation but direct", "stimulation but direct interaction", "but direct interaction with the", "direct interaction with the receptor", "interaction with the receptor has", "with the receptor has not", "the receptor has not been", "receptor has not been demonstrated.", "has not been demonstrated. co", "not been demonstrated. co precipitation", "been demonstrated. co precipitation of", "demonstrated. co precipitation of p46", "co precipitation of p46 and", "precipitation of p46 and p52", "of p46 and p52 with", "p46 and p52 with the", "and p52 with the fgfr2", "p52 with the fgfr2 iiic", "with the fgfr2 iiic receptor", "the fgfr2 iiic receptor has", "fgfr2 iiic receptor has been", "iiic receptor has been reported", "has been reported but", "been reported but this", "reported but this interaction", "but this interaction is thought", "this interaction is thought to", "interaction is thought to be", "is thought to be indirect", "to be indirect possibly", "be indirect possibly mediated", "indirect possibly mediated by", "mediated by src. consistent", "by src. consistent with", "src. consistent with this", "consistent with this co", "with this co precipitation", "this co precipitation of", "co precipitation of shc1 and", "precipitation of shc1 and fgfr1", "of shc1 and fgfr1 iiic", "shc1 and fgfr1 iiic is", "and fgfr1 iiic is seen", "fgfr1 iiic is seen in", "iiic is seen in mammalian", "is seen in mammalian cells", "seen in mammalian cells expressing", "in mammalian cells expressing v", "mammalian cells expressing v src.", "expressing v src. the", "v src. the p66", "src. the p66 isoform", "the p66 isoform of shc1", "p66 isoform of shc1 has", "isoform of shc1 has also", "of shc1 has also been", "shc1 has also been co", "has also been co precipitated", "also been co precipitated with", "been co precipitated with fgfr3", "precipitated with fgfr3 but", "with fgfr3 but this", "fgfr3 but this occurs", "but this occurs independently of", "this occurs independently of receptor", "occurs independently of receptor stimulation", "of receptor stimulation and", "receptor stimulation and the", "stimulation and the p66", "and the p66 isoform not", "the p66 isoform not been", "p66 isoform not been shown", "isoform not been shown to", "not been shown to undergo", "been shown to undergo fgf", "shown to undergo fgf dependent", "to undergo fgf dependent phosphorylation.", "fgf dependent phosphorylation. shc1", "dependent phosphorylation. shc1 has", "phosphorylation. shc1 has been", "shc1 has been shown to", "has been shown to associate", "been shown to associate with", "shown to associate with grb2", "to associate with grb2 and", "associate with grb2 and sos1", "with grb2 and sos1 in", "grb2 and sos1 in response", "and sos1 in response to", "sos1 in response to fgf", "to fgf stimulation suggesting", "fgf stimulation suggesting that", "stimulation suggesting that the", "suggesting that the recruitment of", "that the recruitment of shc1", "the recruitment of shc1 may", "recruitment of shc1 may contribute", "of shc1 may contribute to", "shc1 may contribute to activation", "may contribute to activation of", "contribute to activation of the", "to activation of the mapk", "activation of the mapk cascade", "of the mapk cascade downstream", "the mapk cascade downstream of", "mapk cascade downstream of fgfr." ] }, { "record_id": "GLY_000594_1_1052", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654720", "r hsa", "hsa 5654720", "r hsa 5654720" ] }, { "record_id": "GLY_000594_1_1052", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pi 3k", "3k cascade:fgfr4", "pi 3k cascade:fgfr4", "the ability", "ability of", "of growth", "growth factors", "factors to", "to protect", "protect from", "from apoptosis", "apoptosis is", "is primarily", "primarily due", "due to", "to the", "the activation", "activation of", "of the", "the akt", "akt survival", "survival pathway.", "pathway. p", "p i", "i 3", "3 kinase", "kinase dependent", "dependent activation", "of pdk", "pdk leads", "leads to", "of akt", "akt which", "which in", "in turn", "turn affects", "affects the", "the 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is primarily due", "is primarily due to", "primarily due to the", "due to the activation", "to the activation of", "the activation of the", "activation of the akt", "of the akt survival", "the akt survival pathway.", "akt survival pathway. p", "survival pathway. p i", "pathway. p i 3", "p i 3 kinase", "i 3 kinase dependent", "3 kinase dependent activation", "kinase dependent activation of", "dependent activation of pdk", "activation of pdk leads", "of pdk leads to", "pdk leads to the", "leads to the activation", "the activation of akt", "activation of akt which", "of akt which in", "akt which in turn", "which in turn affects", "in turn affects the", "turn affects the activity", "affects the activity or", "the activity or expression", "activity or expression of", "or expression of pro", "expression of pro apoptotic", "of pro apoptotic factors", "apoptotic factors which", "factors which contribute", "which contribute to protection", "contribute to protection from", "to protection from 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survival pathway. p", "akt survival pathway. p i", "survival pathway. p i 3", "pathway. p i 3 kinase", "p i 3 kinase dependent", "i 3 kinase dependent activation", "3 kinase dependent activation of", "kinase dependent activation of pdk", "dependent activation of pdk leads", "activation of pdk leads to", "of pdk leads to the", "pdk leads to the activation", "leads to the activation of", "to the activation of akt", "the activation of akt which", "activation of akt which in", "of akt which in turn", "akt which in turn affects", "which in turn affects the", "in turn affects the activity", "turn affects the activity or", "affects the activity or expression", "the activity or expression of", "activity or expression of pro", "or expression of pro apoptotic", "expression of pro apoptotic factors", "pro apoptotic factors which", "apoptotic factors which contribute", "factors which contribute to", "which contribute to protection from", "contribute to protection from apoptosis.", "to protection from apoptosis. akt", "protection from apoptosis. akt activation", "from apoptosis. akt activation also", "apoptosis. akt activation also blocks", "akt activation also blocks the", "activation also blocks the activity", "also blocks the activity of", "blocks the activity of gsk", "the activity of gsk 3b", "activity of gsk 3b which", "of gsk 3b which could", "gsk 3b which could lead", "3b which could lead to", "which could lead to additional", "could lead to additional antiapoptotic", "lead to additional antiapoptotic signals." ] }, { "record_id": "GLY_000594_1_1053", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654726", "r hsa", "hsa 5654726", "r hsa 5654726" ] }, { "record_id": "GLY_000594_1_1053", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of fgfr1", "fgfr1 signaling", "negative regulation of", "regulation of fgfr1", "of fgfr1 signaling", 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the action", "the action of", "action of dual", "of dual specificity", "dual specificity phosphatases", "phosphatases il17rd/sef", "il17rd/sef sprouty", "sprouty and spred", "and spred proteins.", "proteins. a", "a number of", "number of these", "of these inhibitors", "these inhibitors are", "inhibitors are themselves", "are themselves transcriptional", "themselves transcriptional targets", "transcriptional targets of", "targets of the", "of the activated", "the activated fgfr", "activated fgfr pathway.", "once activated the", "activated the fgfr", "the fgfr signaling pathway", "fgfr signaling pathway is", "signaling pathway is regulated", "pathway is regulated by", "is regulated by numerous", "regulated by numerous negative", "by numerous negative feedback", "numerous negative feedback mechanisms.", "feedback mechanisms. these", "mechanisms. these include", "these include downregulation of", "include downregulation of receptors", "downregulation of receptors through", "of receptors 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"inhibitors are themselves transcriptional", "are themselves transcriptional targets", "themselves transcriptional targets of", "transcriptional targets of the", "targets of the activated", "of the activated fgfr", "the activated fgfr pathway.", "once activated the fgfr", "activated the fgfr signaling", "the fgfr signaling pathway is", "fgfr signaling pathway is regulated", "signaling pathway is regulated by", "pathway is regulated by numerous", "is regulated by numerous negative", "regulated by numerous negative feedback", "by numerous negative feedback mechanisms.", "negative feedback mechanisms. these", "feedback mechanisms. these include", "mechanisms. these include downregulation", "these include downregulation of receptors", "include downregulation of receptors through", "downregulation of receptors through cbl", "of receptors through cbl mediated", "receptors through cbl mediated ubiquitination", "through cbl mediated ubiquitination and", "cbl mediated ubiquitination and endocytosis", "ubiquitination and endocytosis erk", "and endocytosis erk mediated", "endocytosis erk mediated inhibition", "erk mediated inhibition of frs2", "mediated inhibition of frs2 tyrosine", "inhibition of frs2 tyrosine phosphorylation", "of frs2 tyrosine phosphorylation and", "frs2 tyrosine phosphorylation and the", "tyrosine phosphorylation and the attenuation", "phosphorylation and the attenuation of", "and the attenuation of erk", "the attenuation of erk signaling", "attenuation of erk signaling through", "of erk signaling through the", "erk signaling through the action", "signaling through the action of", "through the action of dual", "the action of dual specificity", "action of dual specificity phosphatases", "dual specificity phosphatases il17rd/sef", "phosphatases il17rd/sef sprouty", "il17rd/sef sprouty and spred", "and spred proteins. a", "spred proteins. a number", "proteins. a number of", "a number of these inhibitors", "number of these inhibitors are", "of these inhibitors are themselves", "these inhibitors are themselves transcriptional", "inhibitors are themselves transcriptional targets", "are themselves transcriptional targets of", "themselves transcriptional targets of the", "transcriptional targets of the activated", "targets of the activated fgfr", "of the activated fgfr pathway." ] }, { "record_id": "GLY_000594_1_1054", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5654727", "r hsa", "hsa 5654727", "r hsa 5654727" ] }, { "record_id": "GLY_000594_1_1054", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of fgfr2", "fgfr2 signaling", "negative regulation of", "regulation of fgfr2", "of fgfr2 signaling", "negative regulation of fgfr2", "regulation of fgfr2 signaling", "negative regulation of fgfr2 signaling", "once activated", "the fgfr", "fgfr signaling", "signaling pathway", "pathway is", "is regulated", "regulated by", "by numerous", "numerous negative", "negative feedback", "feedback mechanisms.", "these include", "include downregulation", "downregulation of", "of receptors", "receptors through", "through cbl", "cbl mediated", "mediated ubiquitination", "ubiquitination and", "and endocytosis", "erk mediated", "mediated inhibition", "inhibition of", "of frs2", "frs2 tyrosine", "tyrosine phosphorylation", "phosphorylation and", "and the", "the attenuation", "attenuation of", "of erk", "erk signaling", "signaling through", "through the", "the action", "action of", "of dual", "dual specificity", "specificity phosphatases", "sprouty and", "and spred", "spred proteins.", "a number", "number of", "of these", "these inhibitors", "inhibitors are", "are themselves", "themselves transcriptional", "transcriptional targets", "targets of", "of the", "the activated", "activated fgfr", "fgfr pathway.", "activated the", "the fgfr signaling", "fgfr signaling pathway", "signaling pathway is", "pathway 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number of", "number of these", "of these inhibitors", "these inhibitors are", "inhibitors are themselves", "are themselves transcriptional", "themselves transcriptional targets", "transcriptional targets of", "targets of the", "of the activated", "the activated fgfr", "activated fgfr pathway.", "once activated the", "activated the fgfr", "the fgfr signaling pathway", "fgfr signaling pathway is", "signaling pathway is regulated", "pathway is regulated by", "is regulated by numerous", "regulated by numerous negative", "by numerous negative feedback", "numerous negative feedback mechanisms.", "feedback mechanisms. these", "mechanisms. these include", "these include downregulation of", "include downregulation of receptors", "downregulation of receptors through", "of receptors through cbl", "receptors through cbl mediated", "through cbl mediated ubiquitination", "cbl mediated ubiquitination and", "mediated ubiquitination and endocytosis", "and endocytosis erk", "endocytosis erk mediated", 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activated fgfr pathway.", "once activated the fgfr", "activated the fgfr signaling", "the fgfr signaling pathway is", "fgfr signaling pathway is regulated", "signaling pathway is regulated by", "pathway is regulated by numerous", "is regulated by numerous negative", "regulated by numerous negative feedback", "by numerous negative feedback mechanisms.", "negative feedback mechanisms. these", "feedback mechanisms. these include", "mechanisms. these include downregulation", "these include downregulation of receptors", "include downregulation of receptors through", "downregulation of receptors through cbl", "of receptors through cbl mediated", "receptors through cbl mediated ubiquitination", "through cbl mediated ubiquitination and", "cbl mediated ubiquitination and endocytosis", "ubiquitination and endocytosis erk", "and endocytosis erk mediated", "endocytosis erk mediated inhibition", "erk mediated inhibition of frs2", "mediated inhibition of frs2 tyrosine", "inhibition of frs2 tyrosine 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"jackson weiss", "crouzon and", "and beare", "beare stevensen", "stevensen cutis", "cutis gyrata", "gyrata syndromes.", "these autosomal", "autosomal dominant", "dominant skeletal", "skeletal disorders", "disorders are", "are characterized", "characterized by", "by premature", "premature fusion", "fusion of", "of several", "several sutures", "sutures in", "the skull", "and in", "in some", "some cases", "cases also", "also involve", "involve syndactyly", "abnormal bone", "bone fusions", "fusions in", "the hands", "hands and", "and feet", "reviewed in", "in webster", "webster and", "and donoghue", "2007 .", ".

              activating", "

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              activating", ".

              activating fgfr2", "

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              activating fgfr2", ".

              activating fgfr2 mutations", "

              activating fgfr2 mutations arising", "fgfr2 mutations arising somatically", "mutations arising somatically have", "arising somatically have been", "somatically have been linked", "have been linked to", "been linked to the", "linked to the development", "to the development of", "the development of gastric", "development of gastric and", "of gastric and endometrial", "gastric and endometrial cancers", "endometrial cancers reviewed", "cancers reviewed in", "reviewed in greulich and", "in greulich and pollock", "and pollock 2011", "wesche 2011 .", "2011 . many", ". many of", "many of these mutations", "of these mutations are", "these mutations are similar", "mutations are similar or", "are similar or identical", "similar or identical to", "or identical to those", "identical to those that", "to those that contribute", "those that contribute to", "that contribute to the", "contribute to the autosomal", "to the autosomal disorders", "the autosomal disorders described", 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these", "gyrata syndromes. these autosomal", "syndromes. these autosomal dominant", "these autosomal dominant skeletal disorders", "autosomal dominant skeletal disorders are", "dominant skeletal disorders are characterized", "skeletal disorders are characterized by", "disorders are characterized by premature", "are characterized by premature fusion", "characterized by premature fusion of", "by premature fusion of several", "premature fusion of several sutures", "fusion of several sutures in", "of several sutures in the", "several sutures in the skull", "in the skull and", "the skull and in", "skull and in some", "and in some cases also", "in some cases also involve", "some cases also involve syndactyly", "also involve syndactyly abnormal", "involve syndactyly abnormal bone", "syndactyly abnormal bone fusions", "abnormal bone fusions in the", "bone fusions in the hands", "fusions in the hands and", "in the hands and feet", "and feet reviewed", "feet reviewed in", "reviewed in webster and donoghue", "webster and donoghue 1997", "donoghue 1997 burke", "1997 burke 1998", "burke 1998 cunningham", "1998 cunningham 2007", "cunningham 2007 .

              activating", "2007 .

              activating fgfr2 mutations", ".

              activating fgfr2 mutations arising", "

              activating fgfr2 mutations arising somatically", "fgfr2 mutations arising somatically have", "mutations arising somatically have been", "arising somatically have been linked", "somatically have been linked to", "have been linked to the", "been linked to the development", "linked to the development of", "to the development of gastric", "the development of gastric and", "development of gastric and endometrial", "of gastric and endometrial cancers", "and endometrial cancers reviewed", "endometrial cancers reviewed in", "cancers reviewed in greulich", "reviewed in greulich and pollock", "greulich and pollock 2011", "pollock 2011 wesche", "2011 wesche 2011", "2011 . many of", ". many of these", "many of these mutations are", "of these mutations are similar", "these mutations are similar or", "mutations are similar or identical", "are similar or identical to", "similar or identical to those", "or identical to those that", "identical to those that contribute", "to those that contribute to", "those that contribute to the", "that contribute to the autosomal", "contribute to the autosomal disorders", "to the autosomal disorders described", "the autosomal disorders described above.", "disorders described above. notably", "above. notably loss", "notably loss of function", "loss of function mutations in", "of function mutations in fgfr2", "function mutations in fgfr2 have", "mutations in fgfr2 have also", "in fgfr2 have also been", "fgfr2 have also been recently", "have also been recently described", "also been recently described in", "been recently described in melanoma", "described in melanoma gartside", "melanoma gartside 2009", "2009 . fgfr2 may", ". fgfr2 may also", "fgfr2 may also contribute to", "may also contribute to tumorigenesis", "also contribute to tumorigenesis through", "contribute to tumorigenesis through overexpression", "tumorigenesis through overexpression as", "through overexpression as fgfr2", "overexpression as fgfr2 has", "as fgfr2 has been identified", "fgfr2 has been identified as", "has been identified as a", "been identified as a target", "identified as a target of", "as a target of gene", "a target of gene amplification", "target of gene amplification in", "of gene amplification in gastric", "gene amplification in gastric and", "amplification in gastric and breast", "in gastric and breast cancers", "and breast cancers kunii", "cancers kunii 2008", "kunii 2008 takeda", "2008 takeda 2007" ] }, { "record_id": "GLY_000594_1_1058", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5655291", "r hsa", "hsa 5655291", "r hsa 5655291" ] }, { "record_id": "GLY_000594_1_1058", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by fgfr4", "fgfr4 in", "in disease", "signaling by fgfr4", "by fgfr4 in", "fgfr4 in disease", "signaling by fgfr4 in", "by fgfr4 in disease", "signaling by fgfr4 in disease", "fgfr4 is", "is perhaps", "perhaps the", "the least", "least well", "well studied", "studied of", "of the", "the fgf", "fgf receptors", "and unlike", "unlike the", "the case", "case for", "for the", "the other", "other fgfr", "fgfr genes", "mutations in", "in fgfr4", "fgfr4 are", "are not", "not known", "known to", "to be", "be associated", "associated with", "with any", "any developmental", "developmental disorders.", "somatically arising", "arising mutations", "in the", "the fgfr4", "fgfr4 coding", "coding sequence", "sequence have", "have begun", "begun to", "be identified", "identified in", "in some", "some cancers.", "8% of", "of rhabdomyosarcomas", "rhabdomyosarcomas have", "have activating", "activating mutations", "the kinase", "kinase domain", "domain of", "of fgfr4.", "two of", "of these", "these mutations", "paralogous to", "to the", "the fgfr2", "fgfr2 n550k", "n550k allele", "allele found", "found in", "in endometrial", "endometrial cancers", "and v550e", "have been", "been shown", "shown to", "to support", "support the", "the oncogenic", "oncogenic transformation", "transformation of", "of nih", "nih 3t3", "3t3 cells", "2009 .", "an fgfr4", "fgfr4 y367c", "y367c mutation", "mutation has", "has also", "also been", "been identified", "in breast", "breast cancers", "mutations of", "of paralogous", "paralogous residues", "residues in", "in fgfr2", "fgfr2 and", "and fgfr3", "fgfr3 are", "are associated", "with both", "both skeletal", "skeletal dysplasias", "dysplasias and", "and the", "the development", "development of", "of diverse", "diverse cancers", "2001 .


              finally", "a snp", "snp at", "at position", "position 388", "388 of", "of fgfr4", "is associated", "with aggressive", "aggressive disease", "disease development.", "expression of", "the g388r", "g388r allele", "allele in", "colorectal and", "and prostate", "prostate cancers", "cancers is", "is correlated", "correlated with", "with rapid", "rapid progression", "progression times", "times and", "and increased", "increased rates", "rates of", "of recurrence", "recurrence and", "and metastasis", "2004 .", "fgfr4 is perhaps", "is perhaps the", "perhaps the least", "the least well", "least well studied", "well studied of", "studied of the", "of the fgf", "the fgf receptors", "receptors and", "and unlike the", "unlike the case", "the case for", "case for the", "for the other", "the other fgfr", "other fgfr genes", "genes mutations", "mutations in fgfr4", "in fgfr4 are", "fgfr4 are not", "are not known", "not known to", "known to be", "to be associated", "be associated with", "associated with any", "with any developmental", "any developmental disorders.", "disorders. recently", "recently however", "however somatically", "somatically arising mutations", "arising mutations in", "mutations in the", "in the fgfr4", "the fgfr4 coding", "fgfr4 coding sequence", "coding sequence have", "sequence have begun", "have begun to", "begun to be", "to be identified", "be identified in", "identified in some", "in some cancers.", "cancers. 8%", "8% of rhabdomyosarcomas", "of rhabdomyosarcomas have", "rhabdomyosarcomas have activating", "have activating mutations", "activating mutations in", "in the kinase", "the kinase domain", "kinase domain of", "domain of fgfr4.", "fgfr4. two", "two of these", "of these mutations", "n535k paralogous", "paralogous to the", "to the fgfr2", "the fgfr2 n550k", "fgfr2 n550k allele", "n550k allele found", "allele found in", "found in endometrial", "in endometrial cancers", "cancers and", "have been shown", "been shown to", "shown to support", "to support the", "support the oncogenic", "the oncogenic transformation", "oncogenic transformation of", "transformation of nih", "of nih 3t3", "nih 3t3 cells", "cells taylor", "taylor 2009", ". an", "an fgfr4 y367c", "fgfr4 y367c mutation", "y367c mutation has", "mutation has also", "has also been", "also been identified", "been identified in", "identified in breast", "in breast cancers", "cancers ruhe", "ruhe 2007", "2007 roidl", "roidl 2010", "mutations of paralogous", "of paralogous residues", "paralogous residues in", "residues in fgfr2", "in fgfr2 and", "fgfr2 and fgfr3", "and fgfr3 are", "fgfr3 are associated", "are associated with", "associated with both", "with both skeletal", "both skeletal dysplasias", "skeletal dysplasias and", "dysplasias and the", "and the development", "the development of", "development of diverse", "of diverse cancers", "cancers pollock", "pollock 2007", "2007 ruhe", "2007 rousseau", "rousseau 1996", "1996 chesi", "chesi 1997", "1997 2001", ".


              finally a", "a snp at", "snp at position", "at position 388", "position 388 of", "388 of fgfr4", "of fgfr4 is", "fgfr4 is associated", "is associated with", "associated with aggressive", "with aggressive disease", "aggressive disease development.", "development. expression", "expression of the", "of the g388r", "the g388r allele", "g388r allele in", "allele in breast", "breast colorectal", "colorectal and prostate", "and prostate cancers", "prostate cancers is", "cancers is correlated", "is correlated with", "correlated with rapid", "with rapid progression", "rapid progression times", "progression times and", "times and increased", "and increased rates", "increased rates of", "rates of recurrence", "of recurrence and", "recurrence and metastasis", "metastasis bange", "bange 2002", "2002 spinola", "spinola 2005", "2005 wang", "wang 2004", "fgfr4 is perhaps the", "is perhaps the least", "perhaps the least well", "the least well studied", "least well studied of", "well studied of the", "studied of the fgf", "of the fgf receptors", "fgf receptors and", "receptors and unlike", "and unlike the case", "unlike the case for", "the case for the", "case for the other", "for the other fgfr", "the other fgfr genes", "fgfr genes mutations", "genes mutations in", "mutations in fgfr4 are", "in fgfr4 are not", "fgfr4 are not known", "are not known to", "not known to be", "known to be associated", "to be associated with", "be associated with any", "associated with any developmental", "with any developmental disorders.", "developmental disorders. recently", "however somatically arising", "somatically arising mutations in", "arising mutations in the", "mutations in the fgfr4", "in the fgfr4 coding", "the fgfr4 coding sequence", "fgfr4 coding sequence have", "coding sequence have begun", "sequence have begun to", "have begun to be", "begun to be identified", "to be identified in", "be identified in some", "identified in some cancers.", "some cancers. 8%", "cancers. 8% of", "8% of rhabdomyosarcomas have", "of rhabdomyosarcomas have activating", "rhabdomyosarcomas have activating mutations", "have activating mutations in", "activating mutations in the", "mutations in the kinase", "in the kinase domain", "the kinase domain of", "kinase domain of fgfr4.", "of fgfr4. two", "fgfr4. two of", "two of these mutations", "mutations n535k", "n535k paralogous to", "paralogous to the fgfr2", "to the fgfr2 n550k", "the fgfr2 n550k allele", "fgfr2 n550k allele found", "n550k allele found in", "allele found in endometrial", "found in endometrial cancers", "endometrial cancers and", "cancers and v550e", "v550e have", "have been shown to", "been shown to support", "shown to support the", "to support the oncogenic", "support the oncogenic transformation", "the oncogenic transformation of", "oncogenic transformation of nih", "transformation of nih 3t3", "of nih 3t3 cells", "3t3 cells taylor", "taylor 2009 .", "2009 . an", ". an fgfr4", "an fgfr4 y367c mutation", "fgfr4 y367c mutation has", "y367c mutation has also", "mutation has also been", "has also been identified", "also been identified in", "been identified in breast", "identified in breast cancers", "breast cancers ruhe", "2010 mutations", "mutations of paralogous residues", "of paralogous residues in", "paralogous residues in fgfr2", "residues in fgfr2 and", "in fgfr2 and fgfr3", "fgfr2 and fgfr3 are", "and fgfr3 are associated", "fgfr3 are associated with", "are associated with both", "associated with both skeletal", "with both skeletal dysplasias", "both skeletal dysplasias and", "skeletal dysplasias and the", "dysplasias and the development", "and the development of", "the development of diverse", "development of diverse cancers", "diverse cancers pollock", "1997 2001 .


              finally", "2001 .


              finally a", ".


              finally a snp", "a snp at position", "snp at position 388", "at position 388 of", "position 388 of fgfr4", "388 of fgfr4 is", "of fgfr4 is associated", "fgfr4 is associated with", "is associated with aggressive", "associated with aggressive disease", "with aggressive disease development.", "disease development. expression", "development. expression of", "expression of the g388r", "of the g388r allele", "the g388r allele in", "g388r allele in breast", "in breast colorectal", "breast colorectal and", "colorectal and prostate cancers", "and prostate cancers is", "prostate cancers is correlated", "cancers is correlated with", "is correlated with rapid", "correlated with rapid progression", "with rapid progression times", "rapid progression times and", "progression times and increased", "times and increased rates", "and increased rates of", "increased rates of recurrence", "rates of recurrence and", "of recurrence and metastasis", "and metastasis bange", "wang 2004 .", "fgfr4 is perhaps the least", "is perhaps the least well", "perhaps the least well studied", "the least well studied of", "least well studied of the", "well studied of the fgf", "studied of the fgf receptors", "the fgf receptors and", "fgf receptors and unlike", "receptors and unlike the", "and unlike the case for", "unlike the case for the", "the case for the other", "case for the other fgfr", "for the other fgfr genes", "other fgfr genes mutations", "fgfr genes mutations in", "genes mutations in fgfr4", "mutations in fgfr4 are not", "in fgfr4 are not known", "fgfr4 are not known to", "are not known to be", "not known to be associated", "known to be associated with", "to be associated with any", "be associated with any developmental", "associated with any developmental disorders.", "any developmental disorders. recently", "disorders. recently however", "recently however somatically", "however somatically arising mutations", "somatically arising mutations in the", "arising mutations in the fgfr4", "mutations in the fgfr4 coding", "in the fgfr4 coding sequence", "the fgfr4 coding sequence have", "fgfr4 coding sequence have begun", "coding sequence have begun to", "sequence have begun to be", "have begun to be identified", "begun to be identified in", "to be identified in some", "be identified in some cancers.", "in some cancers. 8%", "some cancers. 8% of", "cancers. 8% of rhabdomyosarcomas", "8% of rhabdomyosarcomas have activating", "of rhabdomyosarcomas have activating mutations", "rhabdomyosarcomas have activating mutations in", "have activating mutations in the", "activating mutations in the kinase", "mutations in the kinase domain", "in the kinase domain of", "the kinase domain of fgfr4.", "domain of fgfr4. two", "of fgfr4. two of", "fgfr4. two of these", "these mutations n535k", "n535k paralogous to the", "paralogous to the fgfr2 n550k", "to the fgfr2 n550k allele", "the fgfr2 n550k allele found", "fgfr2 n550k allele found in", "n550k allele found in endometrial", "allele found in endometrial cancers", "in endometrial cancers and", "endometrial cancers and v550e", "and v550e have", "v550e have been", "have been shown to support", "been shown to support the", "shown to support the oncogenic", "to support the oncogenic transformation", "support the oncogenic transformation of", "the oncogenic transformation of nih", "oncogenic transformation of nih 3t3", "transformation of nih 3t3 cells", "nih 3t3 cells taylor", "cells taylor 2009", "2009 . an fgfr4", ". an fgfr4 y367c", "an fgfr4 y367c mutation has", "fgfr4 y367c mutation has also", "y367c mutation has also been", "mutation has also been identified", "has also been identified in", "also been identified in breast", "been identified in breast cancers", "in breast cancers ruhe", "cancers ruhe 2007", "ruhe 2007 roidl", "2007 roidl 2010", "2010 mutations of", "mutations of paralogous residues in", "of paralogous residues in fgfr2", "paralogous residues in fgfr2 and", "residues in fgfr2 and fgfr3", "in fgfr2 and fgfr3 are", "fgfr2 and fgfr3 are associated", "and fgfr3 are associated with", "fgfr3 are associated with both", "are associated with both skeletal", "associated with both skeletal dysplasias", "with both skeletal dysplasias and", "both skeletal dysplasias and the", "skeletal dysplasias and the development", "dysplasias and the development of", "and the development of diverse", "the development of diverse cancers", "of diverse cancers pollock", "cancers pollock 2007", "pollock 2007 ruhe", "2007 ruhe 2007", "ruhe 2007 rousseau", "2007 rousseau 1996", "rousseau 1996 chesi", "1996 chesi 1997", "chesi 1997 2001", "2001 .


              finally a snp", ".


              finally a snp at", "a snp at position 388", "snp at position 388 of", "at position 388 of fgfr4", "position 388 of fgfr4 is", "388 of fgfr4 is associated", "of fgfr4 is associated with", "fgfr4 is associated with aggressive", "is associated with aggressive disease", "associated with aggressive disease development.", "aggressive disease development. expression", "disease development. expression of", "development. expression of the", "expression of the g388r allele", "of the g388r allele in", "the g388r allele in breast", "allele in breast colorectal", "in breast colorectal and", "breast colorectal and prostate", "colorectal and prostate cancers is", "and prostate cancers is correlated", "prostate cancers is correlated with", "cancers is correlated with rapid", "is correlated with rapid progression", "correlated with rapid progression times", "with rapid progression times and", "rapid progression times and increased", "progression times and increased rates", "times and increased rates of", "and increased rates of recurrence", "increased rates of recurrence and", "rates of recurrence and metastasis", "recurrence and metastasis bange", "metastasis bange 2002", "bange 2002 spinola", "2002 spinola 2005", "spinola 2005 wang", "2005 wang 2004" ] }, { "record_id": "GLY_000594_1_1059", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5655862", "r hsa", "hsa 5655862", "r hsa 5655862" ] }, { "record_id": "GLY_000594_1_1059", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translesion synthesis", "synthesis by", "by polk", "translesion synthesis by", "synthesis by polk", "translesion synthesis by polk", "dna polymerase", "polymerase kappa", "is a", "a y", "y family", "family dna", "polymerase that", "that is", "is most", "most efficient", "efficient in", "in translesion", "translesion dna", "dna synthesis", "across oxidation", "oxidation derivatives", "derivatives of", "of dna", "dna bases", "such as", "as thymine", "thymine glycol", "and 8", "8 oxoguanine", "as well", "well as", "as bulky", "bulky dna", "dna adducts", "as benzo", "benzo a", "a pyrene", "pyrene diol", "diol epoxide", "epoxide guanine", "guanine adduct", "bpde g", "zhang et", "et al.", "al. 2000", "fischhaber et", "et al.2002", "avkin et", "al. 2004", "vasquez del", "del carpio", "carpio et", "al. 2009", "yoon et", "al. 2010", "lior hoffmann", "hoffmann et", "al. 2012", "christov et", "al. 2014", "2014 .", ". polk", "polk carries", "carries out", "out tls", "tls by", "by forming", "forming a", "a quaternary", "quaternary complex", "complex with", "with rev1", "rev1 and", "and polz", "at dna", "dna damage", "damage sites", "where polk", "polk simultaneously", "simultaneously binds", "binds rev1", "and monoubiquitinated", "monoubiquitinated pcna", "ohashi et", "unk et", "al. 2002", "bi et", "al. 2006", "2006 .", "polk and", "polz cooperate", "cooperate in", "in the", "the elongation", "elongation of", "of nucleotides", "nucleotides inserted", "inserted opposite", "opposite to", "to lesioned", "lesioned bases", "bases by", "by polk.", "polk. similarly", "similarly to", "to polz", "polk has", "has low", "low processivity", "processivity and", "and is", "is error", "error prone", "prakash et", "2010 .", "dna polymerase kappa", "kappa polk", "polk is", "is a y", "a y family", "y family dna", "family dna polymerase", "dna polymerase that", "polymerase that is", "that is most", "is most efficient", "most efficient in", "efficient in translesion", "in translesion dna", "translesion dna synthesis", "synthesis tls", "tls across", "across oxidation derivatives", "oxidation derivatives of", "derivatives of dna", "of dna bases", "bases such", "such as thymine", "as thymine glycol", "glycol tg", "tg and", "and 8 oxoguanine", "oxoguanine ogua", "as well as", "well as bulky", "as bulky dna", "bulky dna adducts", "adducts such", "such as benzo", "as benzo a", "benzo a pyrene", "a pyrene diol", "pyrene diol epoxide", "diol epoxide guanine", "epoxide guanine adduct", "adduct bpde", "zhang et al.", "et al. 2000", "2000 fischhaber", "fischhaber et al.2002", "al.2002 avkin", "avkin et al.", "et al. 2004", "2004 vasquez", "vasquez del carpio", "del carpio et", "carpio et al.", "et al. 2009", "2009 yoon", "yoon et al.", "et al. 2010", "2010 lior", "lior hoffmann et", "hoffmann et al.", "et al. 2012", "2012 christov", "christov et al.", "2012 yoon", "et al. 2014", "al. 2014 .", "2014 . polk", ". polk carries", "polk carries out", "carries out tls", "out tls by", "tls by forming", "by forming a", "forming a quaternary", "a quaternary complex", "quaternary complex with", "complex with rev1", "with rev1 and", "rev1 and polz", "polz rev3l:mad2l2", "rev3l:mad2l2 at", "at dna damage", "dna damage sites", "sites where", "where polk simultaneously", "polk simultaneously binds", "simultaneously binds rev1", "binds rev1 and", "rev1 and monoubiquitinated", "and monoubiquitinated pcna", "pcna ohashi", "ohashi et al.", "2009 haracska", "haracska unk", "unk et al.", "et al. 2002", "2002 bi", "bi et al.", "et al. 2006", "al. 2006 .", "2006 . polk", ". polk and", "polk and polz", "and polz cooperate", "polz cooperate in", "cooperate in the", "in the elongation", "the elongation of", "elongation of nucleotides", "of nucleotides inserted", "nucleotides inserted opposite", "inserted opposite to", "opposite to lesioned", "to lesioned bases", "lesioned bases by", "bases by polk.", "by polk. similarly", "polk. similarly to", "similarly to polz", "polz polk", "polk has low", "has low processivity", "low processivity and", "processivity and is", "and is error", "is error prone", "prone ohashi", "2000 haracska", "haracska prakash", "prakash et al.", "2002 yoon", "al. 2010 .", "polymerase kappa polk", "polk is a", "is a y family", "a y family dna", "y family dna polymerase", "family dna polymerase that", "dna polymerase that is", "polymerase that is most", "that is most efficient", "is most efficient in", "most efficient in translesion", "efficient in translesion dna", "in translesion dna synthesis", "dna synthesis tls", "tls across oxidation", "across oxidation derivatives of", "oxidation derivatives of dna", "derivatives of dna bases", "dna bases such", "bases such as", "such as thymine glycol", "thymine glycol tg", "tg and 8", "8 oxoguanine ogua", "ogua as", "as well as bulky", "well as bulky dna", "as bulky dna adducts", "dna adducts such", "adducts such as", "such as benzo a", "as benzo a pyrene", "benzo a pyrene diol", "a pyrene diol epoxide", "pyrene diol epoxide guanine", "diol epoxide guanine adduct", "guanine adduct bpde", "adduct bpde g", "g zhang", "zhang et al. 2000", "al. 2000 fischhaber", "2000 fischhaber et", "et al.2002 avkin", "al.2002 avkin et", "avkin et al. 2004", "al. 2004 vasquez", "2004 vasquez del", "vasquez del carpio et", "del carpio et al.", "carpio et al. 2009", "al. 2009 yoon", "2009 yoon et", "yoon et al. 2010", "al. 2010 lior", "2010 lior hoffmann", "lior hoffmann et al.", "hoffmann et al. 2012", "al. 2012 christov", "2012 christov et", "christov et al. 2012", "al. 2012 yoon", "2012 yoon et", "yoon et al. 2014", "et al. 2014 .", "al. 2014 . polk", "2014 . polk carries", ". polk carries out", "polk carries out tls", "carries out tls by", "out tls by forming", "tls by forming a", "by forming a quaternary", "forming a quaternary complex", "a quaternary complex with", "quaternary complex with rev1", "complex with rev1 and", "with rev1 and polz", "and polz rev3l:mad2l2", "rev3l:mad2l2 at dna", "at dna damage sites", "damage sites where", "sites where polk", "where polk simultaneously binds", "polk simultaneously binds rev1", "simultaneously binds rev1 and", "binds rev1 and monoubiquitinated", "rev1 and monoubiquitinated pcna", "monoubiquitinated pcna ohashi", "pcna ohashi et", "ohashi et al. 2009", "al. 2009 haracska", "haracska unk et", "unk et al. 2002", "al. 2002 bi", "2002 bi et", "bi et al. 2006", "et al. 2006 .", "al. 2006 . polk", "2006 . polk and", ". polk and polz", "polk and polz cooperate", "and polz cooperate in", "polz cooperate in the", "cooperate in the elongation", "in the elongation of", "the elongation of nucleotides", "elongation of nucleotides inserted", "of nucleotides inserted opposite", "nucleotides inserted opposite to", "inserted opposite to lesioned", "opposite to lesioned bases", "to lesioned bases by", "lesioned bases by polk.", "bases by polk. similarly", "by polk. similarly to", "polk. similarly to polz", "to polz polk", "polz polk has", "polk has low processivity", "has low processivity and", "low processivity and is", "processivity and is error", "and is error prone", "error prone ohashi", "prone ohashi et", "ohashi et al. 2000", "al. 2000 haracska", "haracska prakash et", "prakash et al. 2002", "al. 2002 yoon", "2002 yoon et", "et al. 2010 .", "dna polymerase kappa polk", "kappa polk is", "polk is a y", "is a y family dna", "a y family dna polymerase", "y family dna polymerase that", "family dna polymerase that is", "dna polymerase that is most", "polymerase that is most efficient", "that is most efficient in", "is most efficient in translesion", "most efficient in translesion dna", "efficient in translesion dna synthesis", "translesion dna synthesis tls", "synthesis tls across", "tls across oxidation derivatives", "across oxidation derivatives of dna", "oxidation derivatives of dna bases", "of dna bases such", "dna bases such as", "bases such as thymine", "as thymine glycol tg", "glycol tg and", "tg and 8 oxoguanine", "and 8 oxoguanine ogua", "ogua as well", "as well as bulky dna", "well as bulky dna adducts", "bulky dna adducts such", "dna adducts such as", "adducts such as benzo", "such as benzo a pyrene", "as benzo a pyrene diol", "benzo a pyrene diol epoxide", "a pyrene diol epoxide guanine", "pyrene diol epoxide guanine adduct", "epoxide guanine adduct bpde", "guanine adduct bpde g", "bpde g zhang", "g zhang et", "et al. 2000 fischhaber", "al. 2000 fischhaber et", "2000 fischhaber et al.2002", "fischhaber et al.2002 avkin", "et al.2002 avkin et", "al.2002 avkin et al.", "et al. 2004 vasquez", "al. 2004 vasquez del", "2004 vasquez del carpio", "vasquez del carpio et al.", "del carpio et al. 2009", "et al. 2009 yoon", "al. 2009 yoon et", "2009 yoon et al.", "et al. 2010 lior", "al. 2010 lior hoffmann", "2010 lior hoffmann et", "lior hoffmann et al. 2012", "et al. 2012 christov", "al. 2012 christov et", "2012 christov et al.", "et al. 2012 yoon", "al. 2012 yoon et", "2012 yoon et al.", "yoon et al. 2014 .", "et al. 2014 . polk", "al. 2014 . polk carries", "2014 . polk carries out", ". polk carries out tls", "polk carries out tls by", "carries out tls by forming", "out tls by forming a", "tls by forming a quaternary", "by forming a quaternary complex", "forming a quaternary complex with", "a quaternary complex with rev1", "quaternary complex with rev1 and", "complex with rev1 and polz", "rev1 and polz rev3l:mad2l2", "polz rev3l:mad2l2 at", "rev3l:mad2l2 at dna damage", "dna damage sites where", "damage sites where polk", "sites where polk simultaneously", "where polk simultaneously binds rev1", "polk simultaneously binds rev1 and", "simultaneously binds rev1 and monoubiquitinated", "binds rev1 and monoubiquitinated pcna", "and monoubiquitinated pcna ohashi", "monoubiquitinated pcna ohashi et", "pcna ohashi et al.", "et al. 2009 haracska", "2009 haracska unk", "haracska unk et al.", "et al. 2002 bi", "al. 2002 bi et", "2002 bi et al.", "bi et al. 2006 .", "et al. 2006 . polk", "al. 2006 . polk and", "2006 . polk and polz", ". polk and polz cooperate", "polk and polz cooperate in", "and polz cooperate in the", "polz cooperate in the elongation", "cooperate in the elongation of", "in the elongation of nucleotides", "the elongation of nucleotides inserted", "elongation of nucleotides inserted opposite", "of nucleotides inserted opposite to", "nucleotides inserted opposite to lesioned", "inserted opposite to lesioned bases", "opposite to lesioned bases by", "to lesioned bases by polk.", "lesioned bases by polk. similarly", "bases by polk. similarly to", "by polk. similarly to polz", "similarly to polz polk", "to polz polk has", "polz polk has low", "polk has low processivity and", "has low processivity and is", "low processivity and is error", "processivity and is error prone", "is error prone ohashi", "error prone ohashi et", "prone ohashi et al.", "et al. 2000 haracska", "2000 haracska prakash", "haracska prakash et al.", "et al. 2002 yoon", "al. 2002 yoon et", "2002 yoon et al.", "yoon et al. 2010 ." ] }, { "record_id": "GLY_000594_1_1060", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5656121", "r hsa", "hsa 5656121", "r hsa 5656121" ] }, { "record_id": "GLY_000594_1_1060", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translesion synthesis", "synthesis by", "by poli", "translesion synthesis by", "synthesis by poli", "translesion synthesis by poli", "dna polymerase", "polymerase iota", "is a", "a y", "y family", "family dna", "polymerase with", "with an", "an active", "active site", "site that", "that favours", "favours hoogsteen", "hoogsteen base", "base pairing", "pairing instead", "instead of", "of watson", "watson crick", "crick base", "base pairing.", "pairing. poli", "poli mediated", "mediated hoogsteen", "pairing and", "and rotation", "rotation of", "of template", "template purines", "purines from", "from anti", "anti to", "to syn", "syn conformation", "conformation serves", "serves as", "as a", "a mechanism", "mechanism to", "to displace", "displace adducts", "adducts on", "on template", "template g", "g or", "or template", "template a", "a that", "that interfere", "interfere with", "with dna", "dna replication", "or to", "to allow", "allow base", "pairing of", "of damaged", "damaged purines", "purines with", "with a", "a disrupted", "disrupted watson", "crick edge", "edge but", "but an", "an intact", "intact hoogsteen", "hoogsteen edge", "nair et", "et al.", "al. 2004", "al. 2006", "2006 .

              poli", ".

              poli is", "is recruited", "recruited to", "to dna", "dna damage", "damage sites", "sites through", "through its", "its interaction", "interaction with", "with pcna", "pcna and", "and rev1.", "rev1. poli", "poli contains", "contains a", "a pip", "pip box", "box and", "and two", "two ubms", "ubiquitin binding", "binding motifs", "that are", "are responsible", "responsible for", "for poli", "poli binding", "binding to", "to monoubiquitinated", "monoubiquitinated pcna", "monoub:k164 pcna", "bienko et", "al. 2005", "haracska et", "bomar et", "al. 2010", "2010 .", ". the", "the interaction", "interaction between", "between poli", "poli and", "and the", "the c", "c terminus", "terminus of", "of rev1", "rev1 is", "is evolutionarily", "evolutionarily conserved", "kosarek et", "al. 2003", "guo et", "ohashi et", "2004 .

              after", ".

              after it", "it incorporates", "incorporates a", "a dnmp", "dnmp opposite", "opposite to", "to damaged", "damaged template", "template base", "poli is", "is unable", "unable to", "to efficiently", "efficiently elongate", "elongate the", "the dna", "dna strand", "strand further.", "further. the", "the elongation", "elongation step", "step is", "is performed", "performed by", "by the", "the polymerase", "polymerase zeta", "zeta complex", "composed of", "of rev3l", "rev3l and", "and mad2l2", "mad2l2 subunits", "johnson et", "al. 2000", "2000 .", "the involvement", "involvement of", "rev1 and", "and polz", "polz in", "in poli", "mediated translesion", "translesion dna", "dna synthesis", "suggests that", "that poli", "poli forms", "forms a", "a quaternary", "quaternary complex", "complex with", "with rev1", "as shown", "shown for", "for polk", "polk and", "and proposed", "proposed for", "for other", "other y", "dna polymerases", "xie et", "al. 2012", "2012 .", "dna polymerase iota", "iota poli", "is a y", "a y family", "y family dna", "family dna polymerase", "dna polymerase with", "polymerase with an", "with an active", "an active site", "active site that", "site that favours", "that favours hoogsteen", "favours hoogsteen base", "hoogsteen base pairing", "base pairing instead", "pairing instead of", "instead of watson", "of watson crick", "watson crick base", "crick base pairing.", "base pairing. poli", "pairing. poli mediated", "poli mediated hoogsteen", "mediated hoogsteen base", "base pairing and", "pairing and rotation", "and rotation of", "rotation of template", "of template purines", "template purines from", "purines from anti", "from anti to", "anti to syn", "to syn conformation", "syn conformation serves", "conformation serves as", "serves as a", "as a mechanism", "a mechanism to", "mechanism to displace", "to displace adducts", "displace adducts on", "adducts on template", "on template g", "template g or", "g or template", "or template a", "template a that", "a that interfere", "that interfere with", "interfere with dna", "with dna replication", "replication or", "or to allow", "to allow base", "allow base pairing", "base pairing of", "pairing of damaged", "of damaged purines", "damaged purines with", "purines with a", "with a disrupted", "a disrupted watson", "disrupted watson crick", "watson crick edge", "crick edge but", "edge but an", "but an intact", "an intact hoogsteen", "intact hoogsteen edge", "edge nair", "nair et al.", "et al. 2004", "2004 nair", "et al. 2006", "al. 2006 .

              poli", "2006 .

              poli is", ".

              poli is recruited", "is recruited to", "recruited to dna", "to dna damage", "dna damage sites", "damage sites through", "sites through its", "through its interaction", "its interaction with", "interaction with pcna", "with pcna and", "pcna and rev1.", "and rev1. poli", "rev1. poli contains", "poli contains a", "contains a pip", "a pip box", "pip box and", "box and two", "and two ubms", "ubms ubiquitin", "ubiquitin binding motifs", "motifs that", "that are responsible", "are responsible for", "responsible for poli", "for poli binding", "poli binding to", "binding to monoubiquitinated", "to monoubiquitinated pcna", "pcna monoub:k164", "bienko et al.", "et al. 2005", "2005 haracska", "haracska et al.", "2005 bomar", "bomar et al.", "et al. 2010", "al. 2010 .", "2010 . the", ". the interaction", "the interaction between", "interaction between poli", "between poli and", "poli and the", "and the c", "the c terminus", "c terminus of", "terminus of rev1", "of rev1 is", "rev1 is evolutionarily", "is evolutionarily conserved", "conserved kosarek", "kosarek et al.", "et al. 2003", "2003 guo", "guo et al.", "2003 ohashi", "ohashi et al.", "al. 2004 .

              after", "2004 .

              after it", ".

              after it incorporates", "it incorporates a", "incorporates a dnmp", "a dnmp opposite", "dnmp opposite to", "opposite to damaged", "to damaged template", "damaged template base", "base poli", "poli is unable", "is unable to", "unable to efficiently", "to efficiently elongate", "efficiently elongate the", "elongate the dna", "the dna strand", "dna strand further.", "strand further. the", "further. the elongation", "the elongation step", "elongation step is", "step is performed", "is performed by", "performed by the", "by the polymerase", "the polymerase zeta", "polymerase zeta complex", "complex polz", "composed of rev3l", "of rev3l and", "rev3l and mad2l2", "and mad2l2 subunits", "subunits johnson", "johnson et al.", "et al. 2000", "al. 2000 .", "2000 . the", ". the involvement", "the involvement of", "involvement of rev1", "of rev1 and", "rev1 and polz", "and polz in", "polz in poli", "in poli mediated", "poli mediated translesion", "mediated translesion dna", "translesion dna synthesis", "synthesis tls", "tls suggests", "suggests that poli", "that poli forms", "poli forms a", "forms a quaternary", "a quaternary complex", "quaternary complex with", "complex with rev1", "with rev1 and", "polz as", "as shown for", "shown for polk", "for polk and", "polk and proposed", "and proposed for", "proposed for other", "for other y", "other y family", "family dna polymerases", "polymerases xie", "xie et al.", "et al. 2012", "al. 2012 .", "polymerase iota poli", "poli is a", "is a y family", "a y family dna", "y family dna polymerase", "family dna polymerase with", "dna polymerase with an", "polymerase with an active", "with an active site", "an active site that", "active site that favours", "site that favours hoogsteen", "that favours hoogsteen base", "favours hoogsteen base pairing", "hoogsteen base pairing instead", "base pairing instead of", "pairing instead of watson", "instead of watson crick", "of watson crick base", "watson crick base pairing.", "crick base pairing. poli", "base pairing. poli mediated", "pairing. poli mediated hoogsteen", "poli mediated hoogsteen base", "mediated hoogsteen base pairing", "hoogsteen base pairing and", "base pairing and rotation", "pairing and rotation of", "and rotation of template", "rotation of template purines", "of template purines from", "template purines from anti", "purines from anti to", "from anti to syn", "anti to syn conformation", "to syn conformation serves", "syn conformation serves as", "conformation serves as a", "serves as a mechanism", "as a mechanism to", "a mechanism to displace", "mechanism to displace adducts", "to displace adducts on", "displace adducts on template", "adducts on template g", "on template g or", "template g or template", "g or template a", "or template a that", "template a that interfere", "a that interfere with", "that interfere with dna", "interfere with dna replication", "dna replication or", "replication or to", "or to allow base", "to allow base pairing", "allow base pairing of", "base pairing of damaged", "pairing of damaged purines", "of damaged purines with", "damaged purines with a", "purines with a disrupted", "with a disrupted watson", "a disrupted watson crick", "disrupted watson crick edge", "watson crick edge but", "crick edge but an", "edge but an intact", "but an intact hoogsteen", "an intact hoogsteen edge", "hoogsteen edge nair", "edge nair et", "nair et al. 2004", "al. 2004 nair", "2004 nair et", "nair et al. 2006", "et al. 2006 .

              poli", "al. 2006 .

              poli is", "2006 .

              poli is recruited", ".

              poli is recruited to", "is recruited to dna", "recruited to dna damage", "to dna damage sites", "dna damage sites through", "damage sites through its", "sites through its interaction", "through its interaction with", "its interaction with pcna", "interaction with pcna and", "with pcna and rev1.", "pcna and rev1. poli", "and rev1. poli contains", "rev1. poli contains a", "poli contains a pip", "contains a pip box", "a pip box and", "pip box and two", "box and two ubms", "two ubms ubiquitin", "ubms ubiquitin binding", "binding motifs that", "motifs that are", "that are responsible for", "are responsible for poli", "responsible for poli binding", "for poli binding to", "poli binding to monoubiquitinated", "binding to monoubiquitinated pcna", "monoubiquitinated pcna monoub:k164", "pcna monoub:k164 pcna", "pcna bienko", "bienko et al. 2005", "al. 2005 haracska", "2005 haracska et", "haracska et al. 2005", "al. 2005 bomar", "2005 bomar et", "bomar et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the interaction", ". the interaction between", "the interaction between poli", "interaction between poli and", "between poli and the", "poli and the c", "and the c terminus", "the c terminus of", "c terminus of rev1", "terminus of rev1 is", "of rev1 is evolutionarily", "rev1 is evolutionarily conserved", "evolutionarily conserved kosarek", "conserved kosarek et", "kosarek et al. 2003", "al. 2003 guo", "2003 guo et", "guo et al. 2003", "al. 2003 ohashi", "2003 ohashi et", "ohashi et al. 2004", "et al. 2004 .

              after", "al. 2004 .

              after it", "2004 .

              after it incorporates", ".

              after it incorporates a", "it incorporates a dnmp", "incorporates a dnmp opposite", "a dnmp opposite to", "dnmp opposite to damaged", "opposite to damaged template", "to damaged template base", "template base poli", "base poli is", "poli is unable to", "is unable to efficiently", "unable to efficiently elongate", "to efficiently elongate the", "efficiently elongate the dna", "elongate the dna strand", "the dna strand further.", "dna strand further. the", "strand further. the elongation", "further. the elongation step", "the elongation step is", "elongation step is performed", "step is performed by", "is performed by the", "performed by the polymerase", "by the polymerase zeta", "the polymerase zeta complex", "zeta complex polz", "polz composed", "composed of rev3l and", "of rev3l and mad2l2", "rev3l and mad2l2 subunits", "mad2l2 subunits johnson", "subunits johnson et", "johnson et al. 2000", "et al. 2000 .", "al. 2000 . the", "2000 . the involvement", ". the involvement of", "the involvement of rev1", "involvement of rev1 and", "of rev1 and polz", "rev1 and polz in", "and polz in poli", "polz in poli mediated", "in poli mediated translesion", "poli mediated translesion dna", "mediated translesion dna synthesis", "dna synthesis tls", "tls suggests that", "suggests that poli forms", "that poli forms a", "poli forms a quaternary", "forms a quaternary complex", "a quaternary complex with", "quaternary complex with rev1", "complex with rev1 and", "with rev1 and polz", "and polz as", "polz as shown", "as shown for polk", "shown for polk and", "for polk and proposed", "polk and proposed for", "and proposed for other", "proposed for other y", "for other y family", "other y family dna", "y family dna polymerases", "dna polymerases xie", "polymerases xie et", "xie et al. 2012", "et al. 2012 .", "dna polymerase iota poli", "iota poli is", "poli is a y", "is a y family dna", "a y family dna polymerase", "y family dna polymerase with", "family dna polymerase with an", "dna polymerase with an active", "polymerase with an active site", "with an active site that", "an active site that favours", "active site that favours hoogsteen", "site that favours hoogsteen base", "that favours hoogsteen base pairing", "favours hoogsteen base pairing instead", "hoogsteen base pairing instead of", "base pairing instead of watson", "pairing instead of watson crick", "instead of watson crick base", "of watson crick base pairing.", "watson crick base pairing. poli", "crick base pairing. poli mediated", "base pairing. poli mediated hoogsteen", "pairing. poli mediated hoogsteen base", "poli mediated hoogsteen base pairing", "mediated hoogsteen base pairing and", "hoogsteen base pairing and rotation", "base pairing and rotation of", "pairing and rotation of template", "and rotation of template purines", "rotation of template purines from", "of template purines from anti", "template purines from anti to", "purines from anti to syn", "from anti to syn conformation", "anti to syn conformation serves", "to syn conformation serves as", "syn conformation serves as a", "conformation serves as a mechanism", "serves as a mechanism to", "as a mechanism to displace", "a mechanism to displace adducts", "mechanism to displace adducts on", "to displace adducts on template", "displace adducts on template g", "adducts on template g or", "on template g or template", "template g or template a", "g or template a that", "or template a that interfere", "template a that interfere with", "a that interfere with dna", "that interfere with dna replication", "with dna replication or", "dna replication or to", "replication or to allow", "or to allow base pairing", "to allow base pairing of", "allow base pairing of damaged", "base pairing of damaged purines", "pairing of damaged purines with", "of damaged purines with a", "damaged purines with a disrupted", "purines with a disrupted watson", "with a disrupted watson crick", "a disrupted watson crick edge", "disrupted watson crick edge but", "watson crick edge but an", "crick edge but an intact", "edge but an intact hoogsteen", "but an intact hoogsteen edge", "intact hoogsteen edge nair", "hoogsteen edge nair et", "edge nair et al.", "et al. 2004 nair", "al. 2004 nair et", "2004 nair et al.", "nair et al. 2006 .

              poli", "et al. 2006 .

              poli is", "al. 2006 .

              poli is recruited", "2006 .

              poli is recruited to", ".

              poli is recruited to dna", "is recruited to dna damage", "recruited to dna damage sites", "to dna damage sites through", "dna damage sites through its", "damage sites through its interaction", "sites through its interaction with", "through its interaction with pcna", "its interaction with pcna and", "interaction with pcna and rev1.", "with pcna and rev1. poli", "pcna and rev1. poli contains", "and rev1. poli contains a", "rev1. poli contains a pip", "poli contains a pip box", "contains a pip box and", "a pip box and two", "pip box and two ubms", "and two ubms ubiquitin", "two ubms ubiquitin binding", "ubms ubiquitin binding motifs", "ubiquitin binding motifs that", "binding motifs that are", "motifs that are responsible", "that are responsible for poli", "are responsible for poli binding", "responsible for poli binding to", "for poli binding to monoubiquitinated", "poli binding to monoubiquitinated pcna", "to monoubiquitinated pcna monoub:k164", "monoubiquitinated pcna monoub:k164 pcna", "monoub:k164 pcna bienko", "pcna bienko et", "et al. 2005 haracska", "al. 2005 haracska et", "2005 haracska et al.", "et al. 2005 bomar", "al. 2005 bomar et", "2005 bomar et al.", "bomar et al. 2010 .", "et al. 2010 . the", "al. 2010 . the interaction", "2010 . the interaction between", ". the interaction between poli", "the interaction between poli and", "interaction between poli and the", "between poli and the c", "poli and the c terminus", "and the c terminus of", "the c terminus of rev1", "c terminus of rev1 is", "terminus of rev1 is evolutionarily", "of rev1 is evolutionarily conserved", "is evolutionarily conserved kosarek", "evolutionarily conserved kosarek et", "conserved kosarek et al.", "et al. 2003 guo", "al. 2003 guo et", "2003 guo et al.", "et al. 2003 ohashi", "al. 2003 ohashi et", "2003 ohashi et al.", "ohashi et al. 2004 .

              after", "et al. 2004 .

              after it", "al. 2004 .

              after it incorporates", "2004 .

              after it incorporates a", ".

              after it incorporates a dnmp", "it incorporates a dnmp opposite", "incorporates a dnmp opposite to", "a dnmp opposite to damaged", "dnmp opposite to damaged template", "opposite to damaged template base", "damaged template base poli", "template base poli is", "base poli is unable", "poli is unable to efficiently", "is unable to efficiently elongate", "unable to efficiently elongate the", "to efficiently elongate the dna", "efficiently elongate the dna strand", "elongate the dna strand further.", "the dna strand further. the", "dna strand further. the elongation", "strand further. the elongation step", "further. the elongation step is", "the elongation step is performed", "elongation step is performed by", "step is performed by the", "is performed by the polymerase", "performed by the polymerase zeta", "by the polymerase zeta complex", "polymerase zeta complex polz", "polz composed of", "composed of rev3l and mad2l2", "of rev3l and mad2l2 subunits", "and mad2l2 subunits johnson", "mad2l2 subunits johnson et", "subunits johnson et al.", "johnson et al. 2000 .", "et al. 2000 . the", "al. 2000 . the involvement", "2000 . the involvement of", ". the involvement of rev1", "the involvement of rev1 and", "involvement of rev1 and polz", "of rev1 and polz in", "rev1 and polz in poli", "and polz in poli mediated", "polz in poli mediated translesion", "in poli mediated translesion dna", "poli mediated translesion dna synthesis", "translesion dna synthesis tls", "synthesis tls suggests", "tls suggests that poli", "suggests that poli forms a", "that poli forms a quaternary", "poli forms a quaternary complex", "forms a quaternary complex with", "a quaternary complex with rev1", "quaternary complex with rev1 and", "complex with rev1 and polz", "rev1 and polz as", "and polz as shown", "polz as shown for", "as shown for polk and", "shown for polk and proposed", "for polk and proposed for", "polk and proposed for other", "and proposed for other y", "proposed for other y family", "for other y family dna", "other y family dna polymerases", "family dna polymerases xie", "dna polymerases xie et", "polymerases xie et al.", "xie et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1061", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5658034", "r hsa", "hsa 5658034", "r hsa 5658034" ] }, { "record_id": "GLY_000594_1_1061", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hhat g278v", "g278v doesn't", "doesn't palmitoylate", "palmitoylate hh", "hh np", "hhat g278v doesn't", "g278v doesn't palmitoylate", "doesn't palmitoylate hh", "palmitoylate hh np", "hhat g278v doesn't palmitoylate", "g278v doesn't palmitoylate hh", "doesn't palmitoylate hh np", "hhat g278v doesn't palmitoylate hh", "g278v doesn't palmitoylate hh np", "a loss", "loss of", "of function", "function mutation", "mutation in", "in hhat", "hhat that", "that abrogates", "abrogates palmitoylation", 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2012 cheng et", "2012 cheng et al.", "cheng et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1064", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5661270", "r hsa", "hsa 5661270", "r hsa 5661270" ] }, { "record_id": "GLY_000594_1_1064", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of xylulose", "xylulose 5", "5 phosphate", "formation of xylulose", "of xylulose 5", "xylulose 5 phosphate", "formation of xylulose 5", "of xylulose 5 phosphate", "formation of xylulose 5 phosphate", "the conversion", "conversion of", "of d", "d glucuronate", "glucuronate to", "to d", "d xylulose", "an intermediate", "intermediate in", "in the", "the pentose", "pentose phosphate", "phosphate pathway", "proceeds via", "via l", "l gulonate", "3 dehydro", "dehydro l", "l xylulose", "and d", "wamelink et", "et al.", "al. 2008", "2008 .", ". d", "glucuronate can", "can be", "be generated", "generated 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"although craf", "also known", "known as", "as raf", "raf 1", "was the", "the first", "first identified", "identified and", "and remains", "remains perhaps", "perhaps the", "the best", "best studied", "braf is", "is most", "most similar", "similar to", "to the", "the raf", "raf expressed", "expressed in", "in other", "other organisms.", "organisms. notably", "activation is", "is more", "more compromised", "compromised in", "in braf", "braf deficient", "deficient cells", "cells than", "than in", "in craf", "craf or", "or araf", "araf deficient", "bonner et", "et al", "mikula et", "huser et", "mercer et", "reviewed in", "in leicht", "leicht et", "matallanas et", "cseh et", "2014 .", ". consistent", "consistent with", "with its", "its important", "important role", "role in", "in mapk", "mapk pathway", "pathway activation", "mutations in", "in the", "the braf", "braf gene", "but not", "not in", "in those", "those for", "for a", "or craf", "are associated", "associated with", "with cancer", "cancer development", "davies et", "2007 .", ". araf", "araf and", "and craf", "craf may", "may have", "have arisen", "arisen through", "through gene", "gene duplication", "duplication events", "and may", "may play", "play additional", "additional roles", "roles in", "mapk independent", "independent signaling", "hindley and", "and kolch", "murakami and", "and morrison", "2001 .
              despite", ".
              despite divergences", "divergences in", "in function", "all mammalian", "mammalian raf", "raf proteins", "proteins share", "share three", "three conserved", "conserved regions", "and each", "each interacts", "interacts with", "with ras", "and mek", "mek proteins", "although with", "with different", "different affinities.", "affinities. the", "the n", "n terminal", "terminal cr1", "cr1 contains", "contains a", "a ras", "ras binding", "binding domain", "and a", "a cysteine", "cysteine rich", "rich domain", "that mediate", "mediate interactions", "interactions with", "and the", "the phospholipid", "phospholipid membrane.", "membrane. cr2", "cr2 contains", "contains inhibitory", "inhibitory phosphorylation", "phosphorylation sites", "sites that", "that impact", "impact ras", "binding and", "and raf", "while the", "the c", "c terminal", "terminal cr3", "cr3 contains", "contains the", "the bi", "bi lobed", "lobed kinase", "kinase domain", "domain with", "its activation", "activation loop", "and an", "an adjacent", "adjacent upstream", "upstream \\n", "\\n terminal", "terminal acidic", "acidic motif\\", "s s/g", "s/g yy", "yy in", "in c", "a raf", "raf respectively", "and ssdd", "ssdd in", "in b", "b raf", "that is", "is required", "required for", "for raf", "tran et", "dhillon et", "chong et", "cutler et", "in matallanas", "2011 .

              regulation", ".

              regulation of", "of raf", "raf activity", "activity involves", "involves multiple", "multiple phosphorylation", "phosphorylation and", "and dephosphorylation", "dephosphorylation events", "intramolecular conformational", "conformational changes", "and heterodimerization", "heterodimerization between", "between raf", "raf monomers", "monomers and", "and changes", "changes to", "to protein", "protein binding", "binding partners", "including scaffolding", "scaffolding proteins", "proteins which", "which bring", "bring pathway", "pathway members", "members together", ". the", "the details", "details of", "of this", "this regulation", "regulation are", "are not", "not completely", "completely known", "known and", "and differ", "differ slightly", "slightly from", "from one", "one raf", "raf isoform", "isoform to", "to another.", "another. briefly", "the inactive", "inactive state", "raf phosphorylation", "phosphorylation on", "on conserved", "conserved serine", "serine residues", "residues in", "in cr2", "cr2 promote", "promote an", "an interaction", "interaction with", "with 14", "14 3", "3 3", "3 dimers", "maintaining the", "the kinase", "kinase in", "in a", "a closed", "closed conformation.", "conformation. upon", "upon ras", "ras activation", "these sites", "sites are", "are dephosphorylated", "allowing the", "raf crd", "crd and", "and rbd", "rbd to", "to bind", "bind ras", "and phospholipids", "facilitating membrane", "membrane recruitment.", "activation requires", "requires homo", "or heterodimerization", "which promotes", "promotes autophosphorylation", "autophosphorylation in", "the activation", "loop of", "of the", "the receiving", "receiving monomer.", "the three", "three isoforms", "only braf", "is able", "able to", "to initiate", "initiate this", "this allosteric", "allosteric activation", "activation of", "of other", "other raf", "hu et", "heidorn et", "garnett et", "2005 .", ". this", "this activity", "activity depends", "depends on", "on negative", "negative charge", "charge in", "acidic region", "yy or", "or ssdd", "adjacent to", "kinase domain.", "domain. in", "this region", "region carries", "carries permanent", "permanent negative", "charge due", "due to", "the presence", "presence of", "the two", "two aspartate", "aspartate residues", "in place", "place of", "the tyrosine", "tyrosine residues", "residues of", "of a", "and craf.", "in addition", "unique to", "to braf", "one of", "the serine", "the nta", "nta is", "is constitutively", "constitutively phosphorylated.", "in this", "region are", "are subject", "subject to", "to phosphorylation", "phosphorylation by", "by activated", "activated mek", "mek downstream", "establishing a", "a positive", "positive feedback", "feedback loop", "loop and", "and allowing", "allowing activated", "activated a", "craf monomers", "monomers to", "to act", "act as", "as transactivators", "transactivators in", "in turn", "in cseh", ". raf", "raf signaling", "signaling is", "is terminated", "terminated through", "through dephosphorylation", "dephosphorylation of", "nta region", "region and", "and phosphorylation", "phosphorylation of", "the residues", "residues that", "mediate the", "the inhibitory", "inhibitory interaction", "promoting a", "a return", "return to", "2014 .
              ", "mammals have three", "have three raf", "three raf isoforms", "isoforms a", "a b", "b and c", "c that", "that are activated", "are activated downstream", "activated downstream of", "downstream of ras", "of ras and", "ras and stimulate", "and stimulate the", "stimulate the mapk", "the mapk pathway.", "mapk pathway. although", "pathway. although craf", "craf also", "also known as", "known as raf", "as raf 1", "1 was", "was the first", "the first identified", "first identified and", "identified and remains", "and remains perhaps", "remains perhaps the", "perhaps the best", "the best studied", "studied braf", "braf is most", "is most similar", "most similar to", "similar to the", "to the raf", "the raf expressed", "raf expressed in", "expressed in other", "in other organisms.", "other organisms. notably", "notably mapk", "mapk erk", "erk activation", "activation is more", "is more compromised", "more compromised in", "compromised in braf", "in braf deficient", "braf deficient cells", "deficient cells than", "cells than in", "than in craf", "in craf or", "craf or araf", "or araf deficient", "araf deficient cells", "cells bonner", "bonner et al", "al 1985", "1985 mikula", "mikula et al", "al 2001", "2001 huser", "huser et al", "2001 mercer", "mercer et al", "al 2002", "2002 reviewed", "reviewed in leicht", "in leicht et", "leicht et al", "al 2007", "2007 matallanas", "matallanas et al", "al 2011", "2011 cseh", "cseh et al", "al 2014", "2014 . consistent", ". consistent with", "consistent with its", "with its important", "its important role", "important role in", "role in mapk", "in mapk pathway", "mapk pathway activation", "activation mutations", "mutations in the", "in the braf", "the braf gene", "gene but", "but not in", "not in those", "in those for", "those for a", "a or", "craf are", "are associated with", "associated with cancer", "with cancer development", "development davies", "davies et al", "2007 . araf", ". araf and", "araf and craf", "and craf may", "craf may have", "may have arisen", "have arisen through", "arisen through gene", "through gene duplication", "gene duplication events", "events and", "and may play", "may play additional", "play additional roles", "additional roles in", "roles in mapk", "in mapk independent", "mapk independent signaling", "signaling hindley", "hindley and kolch", "kolch 2002", "2002 murakami", "murakami and morrison", "morrison 2001", "2001 .
              despite divergences", ".
              despite divergences in", "divergences in function", "function all", "all mammalian raf", "mammalian raf proteins", "raf proteins share", "proteins share three", "share three conserved", "three conserved regions", "regions crs", "crs and", "and each interacts", "each interacts with", "interacts with ras", "with ras and", "ras and mek", "and mek proteins", "proteins although", "although with different", "with different affinities.", "different affinities. the", "affinities. the n", "the n terminal", "n terminal cr1", "terminal cr1 contains", "cr1 contains a", "contains a ras", "a ras binding", "ras binding domain", "domain rbd", "rbd and", "and a cysteine", "a cysteine rich", "cysteine rich domain", "domain crd", "crd that", "that mediate interactions", "mediate interactions with", "interactions with ras", "ras and the", "and the phospholipid", "the phospholipid membrane.", "phospholipid membrane. cr2", "membrane. cr2 contains", "cr2 contains inhibitory", "contains inhibitory phosphorylation", "inhibitory phosphorylation sites", "phosphorylation sites that", "sites that impact", "that impact ras", "impact ras binding", "ras binding and", "binding and raf", "and raf activation", "activation while", "while the c", "the c terminal", "c terminal cr3", "terminal cr3 contains", "cr3 contains the", "contains the bi", "the bi lobed", "bi lobed kinase", "lobed kinase domain", "kinase domain with", "domain with its", "with its activation", "its activation loop", "and an adjacent", "an adjacent upstream", "adjacent upstream \\n", "upstream \\n terminal", "\\n terminal acidic", "terminal acidic motif\\", "motif\\ s", "s s/g yy", "s/g yy in", "yy in c", "c and", "and a raf", "a raf respectively", "respectively and", "and ssdd in", "ssdd in b", "in b raf", "that is required", "is required for", "required for raf", "for raf activation", "activation tran", "tran et al", "al 2005", "2005 dhillon", "dhillon et al", "2002 chong", "chong et al", "2001 cutler", "cutler et al", "al 1998", "1998 chong", "al 2003", "2003 reviewed", "reviewed in matallanas", "in matallanas et", "2011 .

              regulation of", ".

              regulation of raf", "of raf activity", "raf activity involves", "activity involves multiple", "involves multiple phosphorylation", "multiple phosphorylation and", "phosphorylation and dephosphorylation", "and dephosphorylation events", "events intramolecular", "intramolecular conformational changes", "changes homo", "homo and", "and heterodimerization between", "heterodimerization between raf", "between raf monomers", "raf monomers and", "monomers and changes", "and changes to", "changes to protein", "to protein binding", "protein binding partners", "partners including", "including scaffolding proteins", "scaffolding proteins which", "proteins which bring", "which bring pathway", "bring pathway members", "pathway members together", "together reviewed", "2014 . the", ". the details", "the details of", "details of this", "of this regulation", "this regulation are", "regulation are not", "are not completely", "not completely known", "completely known and", "known and differ", "and differ slightly", "differ slightly from", "slightly from one", "from one raf", "one raf isoform", "raf isoform to", "isoform to another.", "to another. briefly", "briefly in", "in the inactive", "the inactive state", "state raf", "raf phosphorylation on", "phosphorylation on conserved", "on conserved serine", "conserved serine residues", "serine residues in", "residues in cr2", "in cr2 promote", "cr2 promote an", "promote an interaction", "an interaction with", "interaction with 14", "with 14 3", "14 3 3", "3 3 dimers", "dimers maintaining", "maintaining the kinase", "the kinase in", "kinase in a", "in a closed", "a closed conformation.", "closed conformation. upon", "conformation. upon ras", "upon ras activation", "activation these", "these sites are", "sites are dephosphorylated", "dephosphorylated allowing", "allowing the raf", "the raf crd", "raf crd and", "crd and rbd", "and rbd to", "rbd to bind", "to bind ras", "bind ras and", "ras and phospholipids", "phospholipids facilitating", "facilitating membrane recruitment.", "recruitment. raf", "raf activation requires", "activation requires homo", "homo or", "heterodimerization which", "which promotes autophosphorylation", "promotes autophosphorylation in", "autophosphorylation in the", "in the activation", "the activation loop", "activation loop of", "loop of the", "of the receiving", "the receiving monomer.", "monomer. of", "of the three", "the three isoforms", "isoforms only", "only braf is", "braf is able", "is able to", "able to initiate", "to initiate this", "initiate this allosteric", "this allosteric activation", "allosteric activation of", "activation of other", "of other raf", "other raf monomers", "monomers hu", "hu et al", "al 2013", "2013 heidorn", "heidorn et al", "al 2010", "2010 garnett", "garnett et al", "2005 . this", ". this activity", "this activity depends", "activity depends on", "depends on negative", "on negative charge", "negative charge in", "charge in the", "in the n", "n terminal acidic", "terminal acidic region", "region nta", "nta s", "s/g yy or", "yy or ssdd", "ssdd adjacent", "adjacent to the", "to the kinase", "the kinase domain.", "kinase domain. in", "domain. in braf", "braf this", "this region carries", "region carries permanent", "carries permanent negative", "permanent negative charge", "negative charge due", "charge due to", "due to the", "to the presence", "the presence of", "presence of the", "of the two", "the two aspartate", "two aspartate residues", "aspartate residues in", "residues in place", "in place of", "place of the", "of the tyrosine", "the tyrosine residues", "tyrosine residues of", "residues of a", "a and", "craf. in", "addition unique", "unique to braf", "braf one", "one of the", "of the serine", "the serine residues", "serine residues of", "residues of the", "of the nta", "the nta is", "nta is constitutively", "is constitutively phosphorylated.", "phosphorylated. in", "craf residues", "residues in this", "in this region", "this region are", "region are subject", "are subject to", "subject to phosphorylation", "to phosphorylation by", "phosphorylation by activated", "by activated mek", "activated mek downstream", "mek downstream of", "downstream of raf", "of raf activation", "activation establishing", "establishing a positive", "a positive feedback", "positive feedback loop", "feedback loop and", "loop and allowing", "and allowing activated", "allowing activated a", "and craf monomers", "craf monomers to", "monomers to act", "to act as", "act as transactivators", "as transactivators in", "transactivators in turn", "turn hu", "2013 reviewed", "reviewed in cseh", "in cseh et", "2014 . raf", ". raf signaling", "raf signaling is", "signaling is terminated", "is terminated through", "terminated through dephosphorylation", "through dephosphorylation of", "dephosphorylation of the", "the nta region", "nta region and", "region and phosphorylation", "and phosphorylation of", "phosphorylation of the", "of the residues", "the residues that", "residues that mediate", "that mediate the", "mediate the inhibitory", "the inhibitory interaction", "inhibitory interaction with", "3 promoting", "promoting a return", "a return to", "return to the", "to the inactive", "state reviewed", "mammals have three raf", "have three raf isoforms", "raf isoforms a", "a b and", "and c that", "c that are", "that are activated downstream", "are activated downstream of", "activated downstream of ras", "downstream of ras and", "of ras and stimulate", "ras and stimulate the", "and stimulate the mapk", "stimulate the mapk pathway.", "the mapk pathway. although", "mapk pathway. although craf", "although craf also", "craf also known", "also known as raf", "known as raf 1", "raf 1 was", "1 was the", "was the first identified", "the first identified and", "first identified and remains", "identified and remains perhaps", "and remains perhaps the", "remains perhaps the best", "perhaps the best studied", "best studied braf", "studied braf is", "braf is most similar", "is most similar to", "most similar to the", "similar to the raf", "to the raf expressed", "the raf expressed in", "raf expressed in other", "expressed in other organisms.", "in other organisms. notably", "organisms. notably mapk", "erk activation is", "activation is more compromised", "is more compromised in", "more compromised in braf", "compromised in braf deficient", "in braf deficient cells", "braf deficient cells than", "deficient cells than in", "cells than in craf", "than in craf or", "in craf or araf", "craf or araf deficient", "or araf deficient cells", "deficient cells bonner", "cells bonner et", "et al 1985", "1985 mikula et", "et al 2001", "2001 huser et", "2001 mercer et", "et al 2002", "2002 reviewed in", "reviewed in leicht et", "in leicht et al", "et al 2007", "2007 matallanas et", "et al 2011", "2011 cseh et", "et al 2014", "al 2014 .", "2014 . consistent with", ". consistent with its", "consistent with its important", "with its important role", "its important role in", "important role in mapk", "role in mapk pathway", "in mapk pathway activation", "pathway activation mutations", "activation mutations in", "mutations in the braf", "in the braf gene", "braf gene but", "gene but not", "but not in those", "not in those for", "in those for a", "for a or", "a or craf", "or craf are", "craf are associated", "are associated with cancer", "associated with cancer development", "cancer development davies", "development davies et", "al 2007 .", "2007 . araf and", ". araf and craf", "araf and craf may", "and craf may have", "craf may have arisen", "may have arisen through", "have arisen through gene", "arisen through gene duplication", "through gene duplication events", "duplication events and", "events and may", "and may play additional", "may play additional roles", "play additional roles in", "additional roles in mapk", "roles in mapk independent", "in mapk independent signaling", "independent signaling hindley", "signaling hindley and", "and kolch 2002", "2002 murakami and", "and morrison 2001", "morrison 2001 .
              despite", "2001 .
              despite divergences in", ".
              despite divergences in function", "in function all", "function all mammalian", "all mammalian raf proteins", "mammalian raf proteins share", "raf proteins share three", "proteins share three conserved", "share three conserved regions", "conserved regions crs", "crs and each", "and each interacts with", "each interacts with ras", "interacts with ras and", "with ras and mek", "ras and mek proteins", "mek proteins although", "proteins although with", "although with different affinities.", "with different affinities. the", "different affinities. the n", "affinities. the n terminal", "the n terminal cr1", "n terminal cr1 contains", "terminal cr1 contains a", "cr1 contains a ras", "contains a ras binding", "a ras binding domain", "binding domain rbd", "rbd and a", "and a cysteine rich", "a cysteine rich domain", "rich domain crd", "crd that mediate", "that mediate interactions with", "mediate interactions with ras", "interactions with ras and", "with ras and the", "ras and the phospholipid", "and the phospholipid membrane.", "the phospholipid membrane. cr2", "phospholipid membrane. cr2 contains", "membrane. cr2 contains inhibitory", "cr2 contains inhibitory phosphorylation", "contains inhibitory phosphorylation sites", "inhibitory phosphorylation sites that", "phosphorylation sites that impact", "sites that impact ras", "that impact ras binding", "impact ras binding and", "ras binding and raf", "binding and raf activation", "raf activation while", "activation while the", "while the c terminal", "the c terminal cr3", "c terminal cr3 contains", "terminal cr3 contains the", "cr3 contains the bi", "contains the bi lobed", "the bi lobed kinase", "bi lobed kinase domain", "lobed kinase domain with", "kinase domain with its", "domain with its activation", "with its activation loop", "activation loop and", "loop and an", "and an adjacent upstream", "an adjacent upstream \\n", "adjacent upstream \\n terminal", "upstream \\n terminal acidic", "\\n terminal acidic motif\\", "acidic motif\\ s", "motif\\ s s/g", "s s/g yy in", "s/g yy in c", "in c and", "c and a", "and a raf respectively", "raf respectively and", "respectively and ssdd", "and ssdd in b", "ssdd in b raf", "raf that", "that is required for", "is required for raf", "required for raf activation", "raf activation tran", "activation tran et", "et al 2005", "2005 dhillon et", "2002 chong et", "2001 cutler et", "et al 1998", "1998 chong et", "et al 2003", "2003 reviewed in", "reviewed in matallanas et", "in matallanas et al", "al 2011 .

              regulation", "2011 .

              regulation of raf", ".

              regulation of raf activity", "of raf activity involves", "raf activity involves multiple", "activity involves multiple phosphorylation", "involves multiple phosphorylation and", "multiple phosphorylation and dephosphorylation", "phosphorylation and dephosphorylation events", "dephosphorylation events intramolecular", "events intramolecular conformational", "conformational changes homo", "homo and heterodimerization", "and heterodimerization between raf", "heterodimerization between raf monomers", "between raf monomers and", "raf monomers and changes", "monomers and changes to", "and changes to protein", "changes to protein binding", "to protein binding partners", "binding partners including", "partners including scaffolding", "including scaffolding proteins which", "scaffolding proteins which bring", "proteins which bring pathway", "which bring pathway members", "bring pathway members together", "members together reviewed", "together reviewed in", "2014 . the details", ". the details of", "the details of this", "details of this regulation", "of this regulation are", "this regulation are not", "regulation are not completely", "are not completely known", "not completely known and", "completely known and differ", "known and differ slightly", "and differ slightly from", "differ slightly from one", "slightly from one raf", "from one raf isoform", "one raf isoform to", "raf isoform to another.", "isoform to another. briefly", "another. briefly in", "briefly in the", "in the inactive state", "inactive state raf", "state raf phosphorylation", "raf phosphorylation on conserved", "phosphorylation on conserved serine", "on conserved serine residues", "conserved serine residues in", "serine residues in cr2", "residues in cr2 promote", "in cr2 promote an", "cr2 promote an interaction", "promote an interaction with", "an interaction with 14", "interaction with 14 3", "with 14 3 3", "14 3 3 dimers", "3 dimers maintaining", "dimers maintaining the", "maintaining the kinase in", "the kinase in a", "kinase in a closed", "in a closed conformation.", "a closed conformation. upon", "closed conformation. upon ras", "conformation. upon ras activation", "ras activation these", "activation these sites", "these sites are dephosphorylated", "are dephosphorylated allowing", "dephosphorylated allowing the", "allowing the raf crd", "the raf crd and", "raf crd and rbd", "crd and rbd to", "and rbd to bind", "rbd to bind ras", "to bind ras and", "bind ras and phospholipids", "and phospholipids facilitating", "phospholipids facilitating membrane", "membrane recruitment. raf", "recruitment. raf activation", "raf activation requires homo", "requires homo or", "homo or heterodimerization", "or heterodimerization which", "heterodimerization which promotes", "which promotes autophosphorylation in", "promotes autophosphorylation in the", "autophosphorylation in the activation", "in the activation loop", "the activation loop of", "activation loop of the", "loop of the receiving", "of the receiving monomer.", "receiving monomer. of", "monomer. of the", "of the three isoforms", "three isoforms only", "isoforms only braf", "only braf is able", "braf is able to", "is able to initiate", "able to initiate this", "to initiate this allosteric", "initiate this allosteric activation", "this allosteric activation of", "allosteric activation of other", "activation of other raf", "of other raf monomers", "raf monomers hu", "monomers hu et", "et al 2013", "2013 heidorn et", "et al 2010", "2010 garnett et", "al 2005 .", "2005 . this activity", ". this activity depends", "this activity depends on", "activity depends on negative", "depends on negative charge", "on negative charge in", "negative charge in the", "charge in the n", "in the n terminal", "the n terminal acidic", "n terminal acidic region", "acidic region nta", "nta s s/g", "s s/g yy or", "s/g yy or ssdd", "or ssdd adjacent", "ssdd adjacent to", "adjacent to the kinase", "to the kinase domain.", "the kinase domain. in", "kinase domain. in braf", "in braf this", "braf this region", "this region carries permanent", "region carries permanent negative", "carries permanent negative charge", "permanent negative charge due", "negative charge due to", "charge due to the", "due to the presence", "to the presence of", "the presence of the", "presence of the two", "of the two aspartate", "the two aspartate residues", "two aspartate residues in", "aspartate residues in place", "residues in place of", "in place of the", "place of the tyrosine", "of the tyrosine residues", "the tyrosine residues of", "tyrosine residues of a", "of a and", "a and craf.", "and craf. in", "craf. in addition", "in addition unique", "addition unique to", "to braf one", "braf one of", "one of the serine", "of the serine residues", "the serine residues of", "serine residues of the", "residues of the nta", "of the nta is", "the nta is constitutively", "nta is constitutively phosphorylated.", "constitutively phosphorylated. in", "phosphorylated. in a", "in a and", "a and craf", "and craf residues", "craf residues in", "residues in this region", "in this region are", "this region are subject", "region are subject to", "are subject to phosphorylation", "subject to phosphorylation by", "to phosphorylation by activated", "phosphorylation by activated mek", "by activated mek downstream", "activated mek downstream of", "mek downstream of raf", "downstream of raf activation", "raf activation establishing", "activation establishing a", "establishing a positive feedback", "a positive feedback loop", "positive feedback loop and", "feedback loop and allowing", "loop and allowing activated", "and allowing activated a", "activated a and", "and craf monomers to", "craf monomers to act", "monomers to act as", "to act as transactivators", "act as transactivators in", "as transactivators in turn", "in turn hu", "turn hu et", "2013 reviewed in", "reviewed in cseh et", "in cseh et al", "2014 . raf signaling", ". raf signaling is", "raf signaling is terminated", "signaling is terminated through", "is terminated through dephosphorylation", "terminated through dephosphorylation of", "through dephosphorylation of the", "dephosphorylation of the nta", "of the nta region", "the nta region and", "nta region and phosphorylation", "region and phosphorylation of", "and phosphorylation of the", "phosphorylation of the residues", "of the residues that", "the residues that mediate", "residues that mediate the", "that mediate the inhibitory", "mediate the inhibitory interaction", "the inhibitory interaction with", "inhibitory interaction with 14", "3 3 promoting", "3 promoting a", "promoting a return to", "a return to the", "return to the inactive", "to the inactive state", "inactive state reviewed", "state reviewed in", "al 2014 .
              ", "mammals have three raf isoforms", "three raf isoforms a", "isoforms a b", "a b and c", "b and c that", "and c that are", "c that are activated", "that are activated downstream of", "are activated downstream of ras", "activated downstream of ras and", "downstream of ras and stimulate", "of ras and stimulate the", "ras and stimulate the mapk", "and stimulate the mapk pathway.", "stimulate the mapk pathway. although", "the mapk pathway. although craf", "pathway. although craf also", "although craf also known", "craf also known as", "also known as raf 1", "as raf 1 was", "raf 1 was the", "1 was the first", "was the first identified and", "the first identified and remains", "first identified and remains perhaps", "identified and remains perhaps the", "and remains perhaps the best", "remains perhaps the best studied", "the best studied braf", "best studied braf is", "studied braf is most", "braf is most similar to", "is most similar to the", "most similar to the raf", "similar to the raf expressed", "to the raf expressed in", "the raf expressed in other", "raf expressed in other organisms.", "expressed in other organisms. notably", "other organisms. notably mapk", "notably mapk erk", "mapk erk activation", "erk activation is more", "activation is more compromised in", "is more compromised in braf", "more compromised in braf deficient", "compromised in braf deficient cells", "in braf deficient cells than", "braf deficient cells than in", "deficient cells than in craf", "cells than in craf or", "than in craf or araf", "in craf or araf deficient", "craf or araf deficient cells", "araf deficient cells bonner", "deficient cells bonner et", "cells bonner et al", "bonner et al 1985", "al 1985 mikula", "1985 mikula et al", "mikula et al 2001", "al 2001 huser", "2001 huser et al", "huser et al 2001", "al 2001 mercer", "2001 mercer et al", "mercer et al 2002", "al 2002 reviewed", "2002 reviewed in leicht", "reviewed in leicht et al", "leicht et al 2007", "al 2007 matallanas", "2007 matallanas et al", "matallanas et al 2011", "al 2011 cseh", "2011 cseh et al", "cseh et al 2014", "et al 2014 .", "al 2014 . consistent", "2014 . consistent with its", ". consistent with its important", "consistent with its important role", "with its important role in", "its important role in mapk", "important role in mapk pathway", "role in mapk pathway activation", "mapk pathway activation mutations", "pathway activation mutations in", "activation mutations in the", "mutations in the braf gene", "the braf gene but", "braf gene but not", "gene but not in", "but not in those for", "not in those for a", "those for a or", "for a or craf", "or craf are associated", "craf are associated with", "are associated with cancer development", "with cancer development davies", "cancer development davies et", "development davies et al", "davies et al 2002", "et al 2007 .", "al 2007 . araf", "2007 . araf and craf", ". araf and craf may", "araf and craf may have", "and craf may have arisen", "craf may have arisen through", "may have arisen through gene", "have arisen through gene duplication", "arisen through gene duplication events", "gene duplication events and", "duplication events and may", "events and may play", "and may play additional roles", "may play additional roles in", "play additional roles in mapk", "additional roles in mapk independent", "roles in mapk independent signaling", "mapk independent signaling hindley", "independent signaling hindley and", "signaling hindley and kolch", "hindley and kolch 2002", "kolch 2002 murakami", "2002 murakami and morrison", "murakami and morrison 2001", "and morrison 2001 .
              despite", "morrison 2001 .
              despite divergences", "2001 .
              despite divergences in function", "divergences in function all", "in function all mammalian", "function all mammalian raf", "all mammalian raf proteins share", "mammalian raf proteins share three", "raf proteins share three conserved", "proteins share three conserved regions", "three conserved regions crs", "regions crs and", "crs and each interacts", "and each interacts with ras", "each interacts with ras and", "interacts with ras and mek", "with ras and mek proteins", "and mek proteins although", "mek proteins although with", "proteins although with different", "although with different affinities. the", "with different affinities. the n", "different affinities. the n terminal", "affinities. the n terminal cr1", "the n terminal cr1 contains", "n terminal cr1 contains a", "terminal cr1 contains a ras", "cr1 contains a ras binding", "contains a ras binding domain", "ras binding domain rbd", "domain rbd and", "rbd and a cysteine", "and a cysteine rich domain", "cysteine rich domain crd", "domain crd that", "crd that mediate interactions", "that mediate interactions with ras", "mediate interactions with ras and", "interactions with ras and the", "with ras and the phospholipid", "ras and the phospholipid membrane.", "and the phospholipid membrane. cr2", "the phospholipid membrane. cr2 contains", "phospholipid membrane. cr2 contains inhibitory", "membrane. cr2 contains inhibitory phosphorylation", "cr2 contains inhibitory phosphorylation sites", "contains inhibitory phosphorylation sites that", "inhibitory phosphorylation sites that impact", "phosphorylation sites that impact ras", "sites that impact ras binding", "that impact ras binding and", "impact ras binding and raf", "ras binding and raf activation", "and raf activation while", "raf activation while the", "activation while the c", "while the c terminal cr3", "the c terminal cr3 contains", "c terminal cr3 contains the", "terminal cr3 contains the bi", "cr3 contains the bi lobed", "contains the bi lobed kinase", "the bi lobed kinase domain", "bi lobed kinase domain with", "lobed kinase domain with its", "kinase domain with its activation", "domain with its activation loop", "its activation loop and", "activation loop and an", "loop and an adjacent", "and an adjacent upstream \\n", "an adjacent upstream \\n terminal", "adjacent upstream \\n terminal acidic", "upstream \\n terminal acidic motif\\", "terminal acidic motif\\ s", "acidic motif\\ s s/g", "motif\\ s s/g yy", "s s/g yy in c", "yy in c and", "in c and a", "c and a raf", "a raf respectively and", "raf respectively and ssdd", "respectively and ssdd in", "and ssdd in b raf", "b raf that", "raf that is", "that is required for raf", "is required for raf activation", "for raf activation tran", "raf activation tran et", "activation tran et al", "tran et al 2005", "al 2005 dhillon", "2005 dhillon et al", "dhillon et al 2002", "al 2002 chong", "2002 chong et al", "chong et al 2001", "al 2001 cutler", "2001 cutler et al", "cutler et al 1998", "al 1998 chong", "1998 chong et al", "chong et al 2003", "al 2003 reviewed", "2003 reviewed in matallanas", "reviewed in matallanas et al", "et al 2011 .

              regulation", "al 2011 .

              regulation of", "2011 .

              regulation of raf activity", ".

              regulation of raf activity involves", "of raf activity involves multiple", "raf activity involves multiple phosphorylation", "activity involves multiple phosphorylation and", "involves multiple phosphorylation and dephosphorylation", "multiple phosphorylation and dephosphorylation events", "and dephosphorylation events intramolecular", "dephosphorylation events intramolecular conformational", "events intramolecular conformational changes", "intramolecular conformational changes homo", "changes homo and", "homo and heterodimerization between", "and heterodimerization between raf monomers", "heterodimerization between raf monomers and", "between raf monomers and changes", "raf monomers and changes to", "monomers and changes to protein", "and changes to protein binding", "changes to protein binding partners", "protein binding partners including", "binding partners including scaffolding", "partners including scaffolding proteins", "including scaffolding proteins which bring", "scaffolding proteins which bring pathway", "proteins which bring pathway members", "which bring pathway members together", "pathway members together reviewed", "members together reviewed in", "together reviewed in matallanas", "al 2014 . the", "2014 . the details of", ". the details of this", "the details of this regulation", "details of this regulation are", "of this regulation are not", "this regulation are not completely", "regulation are not completely known", "are not completely known and", "not completely known and differ", "completely known and differ slightly", "known and differ slightly from", "and differ slightly from one", "differ slightly from one raf", "slightly from one raf isoform", "from one raf isoform to", "one raf isoform to another.", "raf isoform to another. briefly", "to another. briefly in", "another. briefly in the", "briefly in the inactive", "the inactive state raf", "inactive state raf phosphorylation", "state raf phosphorylation on", "raf phosphorylation on conserved serine", "phosphorylation on conserved serine residues", "on conserved serine residues in", "conserved serine residues in cr2", "serine residues in cr2 promote", "residues in cr2 promote an", "in cr2 promote an interaction", "cr2 promote an interaction with", "promote an interaction with 14", "an interaction with 14 3", "interaction with 14 3 3", "with 14 3 3 dimers", "3 3 dimers maintaining", "3 dimers maintaining the", "dimers maintaining the kinase", "maintaining the kinase in a", "the kinase in a closed", "kinase in a closed conformation.", "in a closed conformation. upon", "a closed conformation. upon ras", "closed conformation. upon ras activation", "upon ras activation these", "ras activation these sites", "activation these sites are", "sites are dephosphorylated allowing", "are dephosphorylated allowing the", "dephosphorylated allowing the raf", "allowing the raf crd and", "the raf crd and rbd", "raf crd and rbd to", "crd and rbd to bind", "and rbd to bind ras", "rbd to bind ras and", "to bind ras and phospholipids", "ras and phospholipids facilitating", "and phospholipids facilitating membrane", "phospholipids facilitating membrane recruitment.", "facilitating membrane recruitment. raf", "membrane recruitment. raf activation", "recruitment. raf activation requires", "activation requires homo or", "requires homo or heterodimerization", "or heterodimerization which promotes", "heterodimerization which promotes autophosphorylation", "which promotes autophosphorylation in the", "promotes autophosphorylation in the activation", "autophosphorylation in the activation loop", "in the activation loop of", "the activation loop of the", "activation loop of the receiving", "loop of the receiving monomer.", "the receiving monomer. of", "receiving monomer. of the", "monomer. of the three", "the three isoforms only", "three isoforms only braf", "isoforms only braf is", "only braf is able to", "braf is able to initiate", "is able to initiate this", "able to initiate this allosteric", "to initiate this allosteric activation", "initiate this allosteric activation of", "this allosteric activation of other", "allosteric activation of other raf", "activation of other raf monomers", "other raf monomers hu", "raf monomers hu et", "monomers hu et al", "hu et al 2013", "al 2013 heidorn", "2013 heidorn et al", "heidorn et al 2010", "al 2010 garnett", "2010 garnett et al", "garnett et al 2005", "et al 2005 .", "al 2005 . this", "2005 . this activity depends", ". this activity depends on", "this activity depends on negative", "activity depends on negative charge", "depends on negative charge in", "on negative charge in the", "negative charge in the n", "charge in the n terminal", "in the n terminal acidic", "the n terminal acidic region", "terminal acidic region nta", "region nta s", "nta s s/g yy", "s s/g yy or ssdd", "yy or ssdd adjacent", "or ssdd adjacent to", "ssdd adjacent to the", "adjacent to the kinase domain.", "to the kinase domain. in", "the kinase domain. in braf", "domain. in braf this", "in braf this region", "braf this region carries", "this region carries permanent negative", "region carries permanent negative charge", "carries permanent negative charge due", "permanent negative charge due to", "negative charge due to the", "charge due to the presence", "due to the presence of", "to the presence of the", "the presence of the two", "presence of the two aspartate", "of the two aspartate residues", "the two aspartate residues in", "two aspartate residues in place", "aspartate residues in place of", "residues in place of the", "in place of the tyrosine", "place of the tyrosine residues", "of the tyrosine residues of", "the tyrosine residues of a", "residues of a and", "of a and craf.", "and craf. in addition", "in addition unique to", "addition unique to braf", "unique to braf one", "to braf one of", "braf one of the", "one of the serine residues", "of the serine residues of", "the serine residues of the", "serine residues of the nta", "residues of the nta is", "of the nta is constitutively", "the nta is constitutively phosphorylated.", "is constitutively phosphorylated. in", "constitutively phosphorylated. in a", "in a and craf", "and craf residues in", "craf residues in this", "residues in this region are", "in this region are subject", "this region are subject to", "region are subject to phosphorylation", "are subject to phosphorylation by", "subject to phosphorylation by activated", "to phosphorylation by activated mek", "phosphorylation by activated mek downstream", "by activated mek downstream of", "activated mek downstream of raf", "mek downstream of raf activation", "of raf activation establishing", "raf activation establishing a", "activation establishing a positive", "establishing a positive feedback loop", "a positive feedback loop and", "positive feedback loop and allowing", "feedback loop and allowing activated", "loop and allowing activated a", "allowing activated a and", "activated a and craf", "a and craf monomers", "and craf monomers to act", "craf monomers to act as", "monomers to act as transactivators", "to act as transactivators in", "act as transactivators in turn", "transactivators in turn hu", "in turn hu et", "turn hu et al", "al 2013 reviewed", "2013 reviewed in cseh", "reviewed in cseh et al", "al 2014 . raf", "2014 . raf signaling is", ". raf signaling is terminated", "raf signaling is terminated through", "signaling is terminated through dephosphorylation", "is terminated through dephosphorylation of", "terminated through dephosphorylation of the", "through dephosphorylation of the nta", "dephosphorylation of the nta region", "of the nta region and", "the nta region and phosphorylation", "nta region and phosphorylation of", "region and phosphorylation of the", "and phosphorylation of the residues", "phosphorylation of the residues that", "of the residues that mediate", "the residues that mediate the", "residues that mediate the inhibitory", "that mediate the inhibitory interaction", "mediate the inhibitory interaction with", "the inhibitory interaction with 14", "inhibitory interaction with 14 3", "14 3 3 promoting", "3 3 promoting a", "3 promoting a return", "promoting a return to the", "a return to the inactive", "return to the inactive state", "the inactive state reviewed", "inactive state reviewed in", "state reviewed in matallanas", "et al 2014 .
              " ] }, { "record_id": "GLY_000594_1_1066", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5674135", "r hsa", "hsa 5674135", "r hsa 5674135" ] }, { "record_id": "GLY_000594_1_1066", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "map2k and", "and mapk", "mapk activation", "map2k and mapk", "and mapk activation", "map2k and mapk activation", "activated raf", "raf proteins", "proteins are", "are restricted", "restricted substrate", "substrate kinases", "kinases whose", "whose primary", "primary downstream", "downstream targets", "targets are", "are the", "the two", "two map2k", "map2k proteins", "mapk2k1 and", "and map2k2", "also known", "known as", "as mek1", "mek1 and", "and mek2", "reviewed in", "in roskoski", "2012a .", "phosphorylation of", "of the", "the mapk2k", "mapk2k activation", "activation loop", "loop primes", "primes them", "them to", "to phosphorylate", "phosphorylate the", "the primary", "primary effector", "effector of", "the activated", "activated mapk", "mapk pathway", "two mapk", "mapk proteins", "proteins mapk3", "mapk3 and", "and mapk1", "as erk1", "erk1 and", "and 2", "2 .", "unlike their", "their upstream", "upstream counterparts", "mapk1 catalyze", "catalyze the", "the phosphorylation", "of hundreds", "hundreds of", "of cytoplasmic", "cytoplasmic and", "and nuclear", "nuclear targets", "targets including", "including transcription", "transcription factors", "factors and", "and regulatory", "regulatory molecules", "2012b .", "activation of", "of map2k", "proteins downstream", "downstream of", "of activated", "raf generally", "generally occurs", "occurs in", "in the", "the context", "context of", "of a", "a higher", "higher order", "order scaffolding", "scaffolding complex", "complex that", "that regulates", "regulates the", "the specificity", "specificity and", "and localization", "localization of", "the pathway", "in brown", "brown and", "and sacks", "matallanas et", "et al", "2011 .", "activated raf proteins", "raf proteins are", "proteins are restricted", "are restricted substrate", "restricted substrate kinases", "substrate kinases whose", "kinases whose primary", "whose primary downstream", "primary downstream targets", "downstream targets are", "targets are the", "are the two", "the two map2k", "two map2k proteins", "proteins mapk2k1", "mapk2k1 and map2k2", "map2k2 also", "also known as", "known as mek1", "as mek1 and", "mek1 and mek2", "reviewed in roskoski", "roskoski 2010", "2010 roskoski", "roskoski 2012a", ". phosphorylation", "phosphorylation of the", "of the mapk2k", "the mapk2k activation", "mapk2k activation loop", "activation loop primes", "loop primes them", "primes them to", "them to phosphorylate", "to phosphorylate the", "phosphorylate the primary", "the primary effector", "primary effector of", "effector of the", "of the activated", "the activated mapk", "activated mapk pathway", "pathway the", "the two mapk", "two mapk proteins", "mapk proteins mapk3", "proteins mapk3 and", "mapk3 and mapk1", "mapk1 also", "known as erk1", "as erk1 and", "erk1 and 2", "and 2 .", ". unlike", "unlike their upstream", "their upstream counterparts", "counterparts mapk3", "and mapk1 catalyze", "mapk1 catalyze the", "catalyze the phosphorylation", "the phosphorylation of", "phosphorylation of hundreds", "of hundreds of", "hundreds of cytoplasmic", "of cytoplasmic and", "cytoplasmic and nuclear", "and nuclear targets", "nuclear targets including", "targets including transcription", "including transcription factors", "transcription factors and", "factors and regulatory", "and regulatory molecules", "molecules reviewed", "roskoski 2012b", ". activation", "activation of map2k", "of map2k and", "and mapk proteins", "mapk proteins downstream", "proteins downstream of", "downstream of activated", "of activated raf", "activated raf generally", "raf generally occurs", "generally occurs in", "occurs in the", "in the context", "the context of", "context of a", "of a higher", "a higher order", "higher order scaffolding", "order scaffolding complex", "scaffolding complex that", "complex that regulates", "that regulates the", "regulates the specificity", "the specificity and", "specificity and localization", "and localization of", "localization of the", "of the pathway", "pathway reviewed", "reviewed in brown", "in brown and", "brown and sacks", "sacks 2009", "2009 matallanas", "matallanas et al", "al 2011", "activated raf proteins are", "raf proteins are restricted", "proteins are restricted substrate", "are restricted substrate kinases", "restricted substrate kinases whose", "substrate kinases whose primary", "kinases whose primary downstream", "whose primary downstream targets", "primary downstream targets are", "downstream targets are the", "targets are the two", "are the two map2k", "the two map2k proteins", "map2k proteins mapk2k1", "proteins mapk2k1 and", "and map2k2 also", "map2k2 also known", "also known as mek1", "known as mek1 and", "as mek1 and mek2", "mek2 reviewed", "in roskoski 2010", "roskoski 2012a .", "2012a . phosphorylation", ". phosphorylation of", "phosphorylation of the mapk2k", "of the mapk2k activation", "the mapk2k activation loop", "mapk2k activation loop primes", "activation loop primes them", "loop primes them to", "primes them to phosphorylate", "them to phosphorylate the", "to phosphorylate the primary", "phosphorylate the primary effector", "the primary effector of", "primary effector of the", "effector of the activated", "of the activated mapk", "the activated mapk pathway", "mapk pathway the", "pathway the two", "the two mapk proteins", "two mapk proteins mapk3", "mapk proteins mapk3 and", "proteins mapk3 and mapk1", "and mapk1 also", "mapk1 also known", "also known as erk1", "known as erk1 and", "as erk1 and 2", "erk1 and 2 .", "2 . unlike", ". unlike their", "unlike their upstream counterparts", "upstream counterparts mapk3", "counterparts mapk3 and", "mapk3 and mapk1 catalyze", "and mapk1 catalyze the", "mapk1 catalyze the phosphorylation", "catalyze the phosphorylation of", "the phosphorylation of hundreds", "phosphorylation of hundreds of", "of hundreds of cytoplasmic", "hundreds of cytoplasmic and", "of cytoplasmic and nuclear", "cytoplasmic and nuclear targets", "and nuclear targets including", "nuclear targets including transcription", "targets including transcription factors", "including transcription factors and", "transcription factors and regulatory", "factors and regulatory molecules", "regulatory molecules reviewed", "molecules reviewed in", "in roskoski 2012b", "roskoski 2012b .", "2012b . activation", ". activation of", "activation of map2k and", "of map2k and mapk", "map2k and mapk proteins", "and mapk proteins downstream", "mapk proteins downstream of", "proteins downstream of activated", "downstream of activated raf", "of activated raf generally", "activated raf generally occurs", "raf generally occurs in", "generally occurs in the", "occurs in the context", "in the context of", "the context of a", "context of a higher", "of a higher order", "a higher order scaffolding", "higher order scaffolding complex", "order scaffolding complex that", "scaffolding complex that regulates", "complex that regulates the", "that regulates the specificity", "regulates the specificity and", "the specificity and localization", "specificity and localization of", "and localization of the", "localization of the pathway", "the pathway reviewed", "pathway reviewed in", "reviewed in brown and", "in brown and sacks", "and sacks 2009", "2009 matallanas et", "et al 2011", "al 2011 .", "activated raf proteins are restricted", "raf proteins are restricted substrate", "proteins are restricted substrate kinases", "are restricted substrate kinases whose", "restricted substrate kinases whose primary", "substrate kinases whose primary downstream", "kinases whose primary downstream targets", "whose primary downstream targets are", "primary downstream targets are the", "downstream targets are the two", "targets are the two map2k", "are the two map2k proteins", "two map2k proteins mapk2k1", "map2k proteins mapk2k1 and", "proteins mapk2k1 and map2k2", "mapk2k1 and map2k2 also", "and map2k2 also known", "map2k2 also known as", "also known as mek1 and", "known as mek1 and mek2", "and mek2 reviewed", "mek2 reviewed in", "reviewed in roskoski 2010", "roskoski 2010 roskoski", "2010 roskoski 2012a", "2012a . phosphorylation of", ". phosphorylation of the", "phosphorylation of the mapk2k activation", "of the mapk2k activation loop", "the mapk2k activation loop primes", "mapk2k activation loop primes them", "activation loop primes them to", "loop primes them to phosphorylate", "primes them to phosphorylate the", "them to phosphorylate the primary", "to phosphorylate the primary effector", "phosphorylate the primary effector of", "the primary effector of the", "primary effector of the activated", "effector of the activated mapk", "of the activated mapk pathway", "activated mapk pathway the", "mapk pathway the two", "pathway the two mapk", "the two mapk proteins mapk3", "two mapk proteins mapk3 and", "mapk proteins mapk3 and mapk1", "mapk3 and mapk1 also", "and mapk1 also known", "mapk1 also known as", "also known as erk1 and", "known as erk1 and 2", "as erk1 and 2 .", "and 2 . unlike", "2 . unlike their", ". unlike their upstream", "their upstream counterparts mapk3", "upstream counterparts mapk3 and", "counterparts mapk3 and mapk1", "mapk3 and mapk1 catalyze the", "and mapk1 catalyze the phosphorylation", "mapk1 catalyze the phosphorylation of", "catalyze the phosphorylation of hundreds", "the phosphorylation of hundreds of", "phosphorylation of hundreds of cytoplasmic", "of hundreds of cytoplasmic and", "hundreds of cytoplasmic and nuclear", "of cytoplasmic and nuclear targets", "cytoplasmic and nuclear targets including", "and nuclear targets including transcription", "nuclear targets including transcription factors", "targets including transcription factors and", "including transcription factors and regulatory", "transcription factors and regulatory molecules", "and regulatory molecules reviewed", "regulatory molecules reviewed in", "molecules reviewed in roskoski", "reviewed in roskoski 2012b", "in roskoski 2012b .", "2012b . activation of", ". activation of map2k", "activation of map2k and mapk", "of map2k and mapk proteins", "map2k and mapk proteins downstream", "and mapk proteins downstream of", "mapk proteins downstream of activated", "proteins downstream of activated raf", "downstream of activated raf generally", "of activated raf generally occurs", "activated raf generally occurs in", "raf generally occurs in the", "generally occurs in the context", "occurs in the context of", "in the context of a", "the context of a higher", "context of a higher order", "of a higher order scaffolding", "a higher order scaffolding complex", "higher order scaffolding complex that", "order scaffolding complex that regulates", "scaffolding complex that regulates the", "complex that regulates the specificity", "that regulates the specificity and", "regulates the specificity and localization", "the specificity and localization of", "specificity and localization of the", "and localization of the pathway", "of the pathway reviewed", "the pathway reviewed in", "pathway reviewed in brown", "reviewed in brown and sacks", "brown and sacks 2009", "sacks 2009 matallanas", "2009 matallanas et al", "matallanas et al 2011", "et al 2011 ." ] }, { "record_id": "GLY_000594_1_1067", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5675221", "r hsa", "hsa 5675221", "r hsa 5675221" ] }, { "record_id": "GLY_000594_1_1067", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of mapk", "mapk pathway", "negative regulation of", "regulation of mapk", "of mapk pathway", "negative regulation of mapk", "regulation of mapk pathway", "negative regulation of mapk pathway", "the duration", "duration and", "and extent", "extent of", "of activated", "activated mapk", "mapk signaling", "signaling is", "is regulated", "regulated at", "at many", "many levels", "levels through", "through mechanisms", "mechanisms that", "that include", "include phosphorylation", "phosphorylation and", "and dephosphorylation", "changes to", "to protein", "protein interacting", "interacting partners", "partners and", "and subcellular", "subcellular localization", "reviewed in", "in matallanas", "matallanas et", "et al", "2011 .", "

              activated raf", "raf proteins", "proteins are", "are subject", "subject to", "to mapk", "mapk dependent", "dependent phosphorylation", "phosphorylation that", "that promotes", "promotes the", "the subsequent", "subsequent dephosphorylation", "dephosphorylation of", "of the", "the activation", "activation loop", "loop and", "and nta", "nta region", "terminating raf", "raf kinase", "kinase activity.", "activity. this", "this dephosphorylation", "catalyzed by", "by pp2a", "pp2a and", "and pp5", "primes the", "the raf", "proteins for", "for pka", "pka or", "or akt", "akt mediated", "mediated phosphorylation", "phosphorylation of", "of residues", "residues s259", "s259 and", "and s621", "restoring the", "the 14", "14 3", "3 3", "3 binding", "binding sites", "sites and", "and returning", "returning the", "proteins to", "to the", "the inactive", "inactive state", "von kriegsheim", "kriegsheim et", "dougherty et", ". the", "the phosphorylated", "phosphorylated raf1", "raf1 nta", "nta is", "is also", "also subject", "to additional", "additional regulation", "regulation through", "through binding", "binding to", "the pebp1", "pebp1 protein", "which promotes", "promotes its", "its dissociation", "dissociation from", "from map2k", "map2k substrates", "shin et", "2009 .", ".

              activated", "

              activated mapk", "mapk proteins", "proteins also", "also phosphorylate", "phosphorylate t292", "t292 of", "of map2k1", "this phosphorylation", "phosphorylation limits", "limits the", "the activity", "activity of", "and indirectly", "indirectly affects", "affects map2k2", "map2k2 activity", "activity through", "through by", "by modulating", "modulating the", "the map2k", "map2k heterodimer", "catalanotti et", "2011 .

              dephosphorylation", ".

              dephosphorylation of", "of mapks", "mapks by", "by the", "the dual", "dual specificity", "specificity mapk", "mapk phosphatases", "plays a", "a key", "key role", "role in", "in limiting", "limiting the", "the extent", "of pathway", "pathway activation", "owens et", "in roskoski", "2012b .", "class i", "i dusps", "dusps are", "are localized", "localized in", "in the", "the nucleus", "nucleus and", "and are", "are induced", "induced by", "by activation", "activation of", "the mapk", "establishing a", "a negative", "negative feedback", "feedback loop", "while class", "class ii", "ii dusps", "dusps dephosphorylate", "dephosphorylate cytoplasmic", "cytoplasmic mapks", "in rososki", "2012b .
              mapk", ".
              mapk signaling", "also regulated", "regulated by", "the ras", "ras gap", "gap mediated", "mediated stimulation", "stimulation of", "of intrinsic", "intrinsic ras", "ras gtpase", "gtpase activity", "activity which", "which returns", "returns ras", "ras to", "gdp bound", "bound state", "in king", "king et", "2013 .", "the duration and", "duration and extent", "and extent of", "extent of activated", "of activated mapk", "activated mapk signaling", "mapk signaling is", "signaling is regulated", "is regulated at", "regulated at many", "at many levels", "many levels through", "levels through mechanisms", "through mechanisms that", "mechanisms that include", "that include phosphorylation", "include phosphorylation and", "phosphorylation and dephosphorylation", "dephosphorylation changes", "changes to protein", "to protein interacting", "protein interacting partners", "interacting partners and", "partners and subcellular", "and subcellular localization", "localization reviewed", "reviewed in matallanas", "in matallanas et", "matallanas et al", "al 2011", "

              activated raf proteins", "raf proteins are", "proteins are subject", "are subject to", "subject to mapk", "to mapk dependent", "mapk dependent phosphorylation", "dependent phosphorylation that", "phosphorylation that promotes", "that promotes the", "promotes the subsequent", "the subsequent dephosphorylation", "subsequent dephosphorylation of", "dephosphorylation of the", "of the activation", "the activation loop", "activation loop and", "loop and nta", "and nta region", "region terminating", "terminating raf kinase", "raf kinase activity.", "kinase activity. this", "activity. this dephosphorylation", "dephosphorylation catalyzed", "catalyzed by pp2a", "by pp2a and", "pp2a and pp5", "pp5 primes", "primes the raf", "the raf proteins", "raf proteins for", "proteins for pka", "for pka or", "pka or akt", "or akt mediated", "akt mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of residues", "of residues s259", "residues s259 and", "s259 and s621", "s621 restoring", "restoring the 14", "the 14 3", "14 3 3", "3 3 binding", "3 binding sites", "binding sites and", "sites and returning", "and returning the", "returning the raf", "raf proteins to", "proteins to the", "to the inactive", "the inactive state", "state von", "von kriegsheim et", "kriegsheim et al", "al 2006", "dougherty et al", "al 2005", "2005 reviewed", "2011 . the", ". the phosphorylated", "the phosphorylated raf1", "phosphorylated raf1 nta", "raf1 nta is", "nta is also", "is also subject", "also subject to", "subject to additional", "to additional regulation", "additional regulation through", "regulation through binding", "through binding to", "binding to the", "to the pebp1", "the pebp1 protein", "protein which", "which promotes its", "promotes its dissociation", "its dissociation from", "dissociation from map2k", "from map2k substrates", "substrates shin", "shin et al", "al 2009", "2009 .

              activated", ".

              activated mapk", "

              activated mapk proteins", "mapk proteins also", "proteins also phosphorylate", "also phosphorylate t292", "phosphorylate t292 of", "t292 of map2k1", "map2k1 this", "this phosphorylation limits", "phosphorylation limits the", "limits the activity", "the activity of", "activity of map2k1", "map2k1 and", "and indirectly affects", "indirectly affects map2k2", "affects map2k2 activity", "map2k2 activity through", "activity through by", "through by modulating", "by modulating the", "modulating the activity", "activity of the", "of the map2k", "the map2k heterodimer", "heterodimer catalanotti", "catalanotti et al", "2009 reviewed", "2011 .

              dephosphorylation of", ".

              dephosphorylation of mapks", "of mapks by", "mapks by the", "by the dual", "the dual specificity", "dual specificity mapk", "specificity mapk phosphatases", "phosphatases dusps", "dusps plays", "plays a key", "a key role", "key role in", "role in limiting", "in limiting the", "limiting the extent", "the extent of", "extent of pathway", "of pathway activation", "activation owens", "owens et al", "al 2007", "2007 reviewed", "reviewed in roskoski", "roskoski 2012b", ". class", "class i dusps", "i dusps are", "dusps are localized", "are localized in", "localized in the", "in the nucleus", "the nucleus and", "nucleus and are", "and are induced", "are induced by", "induced by activation", "by activation of", "activation of the", "of the mapk", "the mapk pathway", "pathway establishing", "establishing a negative", "a negative feedback", "negative feedback loop", "loop while", "while class ii", "class ii dusps", "ii dusps dephosphorylate", "dusps dephosphorylate cytoplasmic", "dephosphorylate cytoplasmic mapks", "mapks reviewed", "reviewed in rososki", "rososki 2012b", "2012b .
              mapk signaling", ".
              mapk signaling is", "signaling is also", "is also regulated", "also regulated by", "regulated by the", "by the ras", "the ras gap", "ras gap mediated", "gap mediated stimulation", "mediated stimulation of", "stimulation of intrinsic", "of intrinsic ras", "intrinsic ras gtpase", "ras gtpase activity", "gtpase activity which", "activity which returns", "which returns ras", "returns ras to", "ras to the", "inactive gdp", "gdp bound state", "state reviewed", "reviewed in king", "in king et", "king et al", "al 2013", "the duration and extent", "duration and extent of", "and extent of activated", "extent of activated mapk", "of activated mapk signaling", "activated mapk signaling is", "mapk signaling is regulated", "signaling is regulated at", "is regulated at many", "regulated at many levels", "at many levels through", "many levels through mechanisms", "levels through mechanisms that", "through mechanisms that include", "mechanisms that include phosphorylation", "that include phosphorylation and", "include phosphorylation and dephosphorylation", "and dephosphorylation changes", "dephosphorylation changes to", "changes to protein interacting", "to protein interacting partners", "protein interacting partners and", "interacting partners and subcellular", "partners and subcellular localization", "subcellular localization reviewed", "localization reviewed in", "reviewed in matallanas et", "in matallanas et al", "et al 2011", "al 2011 .", "2011 .

              activated", ".

              activated raf", "

              activated raf proteins are", "raf proteins are subject", "proteins are subject to", "are subject to mapk", "subject to mapk dependent", "to mapk dependent phosphorylation", "mapk dependent phosphorylation that", "dependent phosphorylation that promotes", "phosphorylation that promotes the", "that promotes the subsequent", "promotes the subsequent dephosphorylation", "the subsequent dephosphorylation of", "subsequent dephosphorylation of the", "dephosphorylation of the activation", "of the activation loop", "the activation loop and", "activation loop and nta", "loop and nta region", "nta region terminating", "region terminating raf", "terminating raf kinase activity.", "raf kinase activity. this", "kinase activity. this dephosphorylation", "this dephosphorylation catalyzed", "dephosphorylation catalyzed by", "catalyzed by pp2a and", "by pp2a and pp5", "and pp5 primes", "pp5 primes the", "primes the raf proteins", "the raf proteins for", "raf proteins for pka", "proteins for pka or", "for pka or akt", "pka or akt mediated", "or akt mediated phosphorylation", "akt mediated phosphorylation of", "mediated phosphorylation of residues", "phosphorylation of residues s259", "of residues s259 and", "residues s259 and s621", "and s621 restoring", "s621 restoring the", "restoring the 14 3", "the 14 3 3", "14 3 3 binding", "3 3 binding sites", "3 binding sites and", "binding sites and returning", "sites and returning the", "and returning the raf", "returning the raf proteins", "the raf proteins to", "raf proteins to the", "proteins to the inactive", "to the inactive state", "inactive state von", "state von kriegsheim", "von kriegsheim et al", "et al 2006", "2006 dougherty", "et al 2005", "2005 reviewed in", "2011 . the phosphorylated", ". the phosphorylated raf1", "the phosphorylated raf1 nta", "phosphorylated raf1 nta is", "raf1 nta is also", "nta is also subject", "is also subject to", "also subject to additional", "subject to additional regulation", "to additional regulation through", "additional regulation through binding", "regulation through binding to", "through binding to the", "binding to the pebp1", "to the pebp1 protein", "pebp1 protein which", "protein which promotes", "which promotes its dissociation", "promotes its dissociation from", "its dissociation from map2k", "dissociation from map2k substrates", "map2k substrates shin", "substrates shin et", "et al 2009", "al 2009 .", "2009 .

              activated mapk", ".

              activated mapk proteins", "

              activated mapk proteins also", "mapk proteins also phosphorylate", "proteins also phosphorylate t292", "also phosphorylate t292 of", "phosphorylate t292 of map2k1", "of map2k1 this", "map2k1 this phosphorylation", "this phosphorylation limits the", "phosphorylation limits the activity", "limits the activity of", "the activity of map2k1", "of map2k1 and", "map2k1 and indirectly", "and indirectly affects map2k2", "indirectly affects map2k2 activity", "affects map2k2 activity through", "map2k2 activity through by", "activity through by modulating", "through by modulating the", "by modulating the activity", "modulating the activity of", "the activity of the", "activity of the map2k", "of the map2k heterodimer", "map2k heterodimer catalanotti", "heterodimer catalanotti et", "2009 reviewed in", "al 2011 .

              dephosphorylation", "2011 .

              dephosphorylation of mapks", ".

              dephosphorylation of mapks by", "of mapks by the", "mapks by the dual", "by the dual specificity", "the dual specificity mapk", "dual specificity mapk phosphatases", "mapk phosphatases dusps", "dusps plays a", "plays a key role", "a key role in", "key role in limiting", "role in limiting the", "in limiting the extent", "limiting the extent of", "the extent of pathway", "extent of pathway activation", "pathway activation owens", "activation owens et", "et al 2007", "2007 reviewed in", "in roskoski 2012b", "roskoski 2012b .", "2012b . class", ". class i", "class i dusps are", "i dusps are localized", "dusps are localized in", "are localized in the", "localized in the nucleus", "in the nucleus and", "the nucleus and are", "nucleus and are induced", "and are induced by", "are induced by activation", "induced by activation of", "by activation of the", "activation of the mapk", "of the mapk pathway", "mapk pathway establishing", "pathway establishing a", "establishing a negative feedback", "a negative feedback loop", "feedback loop while", "loop while class", "while class ii dusps", "class ii dusps dephosphorylate", "ii dusps dephosphorylate cytoplasmic", "dusps dephosphorylate cytoplasmic mapks", "cytoplasmic mapks reviewed", "mapks reviewed in", "in rososki 2012b", "rososki 2012b .
              mapk", "2012b .
              mapk signaling is", ".
              mapk signaling is also", "signaling is also regulated", "is also regulated by", "also regulated by the", "regulated by the ras", "by the ras gap", "the ras gap mediated", "ras gap mediated stimulation", "gap mediated stimulation of", "mediated stimulation of intrinsic", "stimulation of intrinsic ras", "of intrinsic ras gtpase", "intrinsic ras gtpase activity", "ras gtpase activity which", "gtpase activity which returns", "activity which returns ras", "which returns ras to", "returns ras to the", "ras to the inactive", "the inactive gdp", "inactive gdp bound", "bound state reviewed", "state reviewed in", "reviewed in king et", "in king et al", "et al 2013", "al 2013 .", "the duration and extent of", "duration and extent of activated", "and extent of activated mapk", "extent of activated mapk signaling", "of activated mapk signaling is", "activated mapk signaling is regulated", "mapk signaling is regulated at", "signaling is regulated at many", "is regulated at many levels", "regulated at many levels through", "at many levels through mechanisms", "many levels through mechanisms that", "levels through mechanisms that include", "through mechanisms that include phosphorylation", "mechanisms that include phosphorylation and", "that include phosphorylation and dephosphorylation", "phosphorylation and dephosphorylation changes", "and dephosphorylation changes to", "dephosphorylation changes to protein", "changes to protein interacting partners", "to protein interacting partners and", "protein interacting partners and subcellular", "interacting partners and subcellular localization", "and subcellular localization reviewed", "subcellular localization reviewed in", "localization reviewed in matallanas", "reviewed in matallanas et al", "matallanas et al 2011", "et al 2011 .", "2011 .

              activated raf", ".

              activated raf proteins", "

              activated raf proteins are subject", "raf proteins are subject to", "proteins are subject to mapk", "are subject to mapk dependent", "subject to mapk dependent phosphorylation", "to mapk dependent phosphorylation that", "mapk dependent phosphorylation that promotes", "dependent phosphorylation that promotes the", "phosphorylation that promotes the subsequent", "that promotes the subsequent dephosphorylation", "promotes the subsequent dephosphorylation of", "the subsequent dephosphorylation of the", "subsequent dephosphorylation of the activation", "dephosphorylation of the activation loop", "of the activation loop and", "the activation loop and nta", "activation loop and nta region", "and nta region terminating", "nta region terminating raf", "region terminating raf kinase", "terminating raf kinase activity. this", "raf kinase activity. this dephosphorylation", "activity. this dephosphorylation catalyzed", "this dephosphorylation catalyzed by", "dephosphorylation catalyzed by pp2a", "catalyzed by pp2a and pp5", "pp2a and pp5 primes", "and pp5 primes the", "pp5 primes the raf", "primes the raf proteins for", "the raf proteins for pka", "raf proteins for pka or", "proteins for pka or akt", "for pka or akt mediated", "pka or akt mediated phosphorylation", "or akt mediated phosphorylation of", "akt mediated phosphorylation of residues", "mediated phosphorylation of residues s259", "phosphorylation of residues s259 and", "of residues s259 and s621", "s259 and s621 restoring", "and s621 restoring the", "s621 restoring the 14", "restoring the 14 3 3", "the 14 3 3 binding", "14 3 3 binding sites", "3 3 binding sites and", "3 binding sites and returning", "binding sites and returning the", "sites and returning the raf", "and returning the raf proteins", "returning the raf proteins to", "the raf proteins to the", "raf proteins to the inactive", "proteins to the inactive state", "the inactive state von", "inactive state von kriegsheim", "state von kriegsheim et", "kriegsheim et al 2006", "2006 dougherty et", "dougherty et al 2005", "al 2005 reviewed", "2005 reviewed in matallanas", "al 2011 . the", "2011 . the phosphorylated raf1", ". the phosphorylated raf1 nta", "the phosphorylated raf1 nta is", "phosphorylated raf1 nta is also", "raf1 nta is also subject", "nta is also subject to", "is also subject to additional", "also subject to additional regulation", "subject to additional regulation through", "to additional regulation through binding", "additional regulation through binding to", "regulation through binding to the", "through binding to the pebp1", "binding to the pebp1 protein", "the pebp1 protein which", "pebp1 protein which promotes", "protein which promotes its", "which promotes its dissociation from", "promotes its dissociation from map2k", "its dissociation from map2k substrates", "from map2k substrates shin", "map2k substrates shin et", "substrates shin et al", "shin et al 2009", "et al 2009 .", "al 2009 .

              activated", "2009 .

              activated mapk proteins", ".

              activated mapk proteins also", "

              activated mapk proteins also phosphorylate", "mapk proteins also phosphorylate t292", "proteins also phosphorylate t292 of", "also phosphorylate t292 of map2k1", "t292 of map2k1 this", "of map2k1 this phosphorylation", "map2k1 this phosphorylation limits", "this phosphorylation limits the activity", "phosphorylation limits the activity of", "limits the activity of map2k1", "activity of map2k1 and", "of map2k1 and indirectly", "map2k1 and indirectly affects", "and indirectly affects map2k2 activity", "indirectly affects map2k2 activity through", "affects map2k2 activity through by", "map2k2 activity through by modulating", "activity through by modulating the", "through by modulating the activity", "by modulating the activity of", "modulating the activity of the", "the activity of the map2k", "activity of the map2k heterodimer", "the map2k heterodimer catalanotti", "map2k heterodimer catalanotti et", "heterodimer catalanotti et al", "catalanotti et al 2009", "al 2009 reviewed", "2009 reviewed in matallanas", "et al 2011 .

              dephosphorylation", "al 2011 .

              dephosphorylation of", "2011 .

              dephosphorylation of mapks by", ".

              dephosphorylation of mapks by the", "of mapks by the dual", "mapks by the dual specificity", "by the dual specificity mapk", "the dual specificity mapk phosphatases", "specificity mapk phosphatases dusps", "phosphatases dusps plays", "dusps plays a key", "plays a key role in", "a key role in limiting", "key role in limiting the", "role in limiting the extent", "in limiting the extent of", "limiting the extent of pathway", "the extent of pathway activation", "of pathway activation owens", "pathway activation owens et", "activation owens et al", "owens et al 2007", "al 2007 reviewed", "2007 reviewed in roskoski", "reviewed in roskoski 2012b", "in roskoski 2012b .", "2012b . class i", ". class i dusps", "class i dusps are localized", "i dusps are localized in", "dusps are localized in the", "are localized in the nucleus", "localized in the nucleus and", "in the nucleus and are", "the nucleus and are induced", "nucleus and are induced by", "and are induced by activation", "are induced by activation of", "induced by activation of the", "by activation of the mapk", "activation of the mapk pathway", "the mapk pathway establishing", "mapk pathway establishing a", "pathway establishing a negative", "establishing a negative feedback loop", "negative feedback loop while", "feedback loop while class", "loop while class ii", "while class ii dusps dephosphorylate", "class ii dusps dephosphorylate cytoplasmic", "ii dusps dephosphorylate cytoplasmic mapks", "dephosphorylate cytoplasmic mapks reviewed", "cytoplasmic mapks reviewed in", "mapks reviewed in rososki", "reviewed in rososki 2012b", "in rososki 2012b .
              mapk", "rososki 2012b .
              mapk signaling", "2012b .
              mapk signaling is also", ".
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failure", "heart failure olson", "failure olson et", "olson et al. 2007", "et al. 2007 .", "al. 2007 . defects", "2007 . defects in", "can also cause hypertrichotic", "also cause hypertrichotic osteochondrodysplasia", "hypertrichotic osteochondrodysplasia cantu", "osteochondrodysplasia cantu syndrome", "cantu syndrome mim:239850", "mim:239850 a", "239850 a", "a rare disorder characterised", "rare disorder characterised by", "disorder characterised by congenital", "characterised by congenital hypertrichosis", "congenital hypertrichosis neonatal", "hypertrichosis neonatal macrosomia", "neonatal macrosomia a", "macrosomia a distinct", "a distinct osteochondrodysplasia and", "distinct osteochondrodysplasia and cardiomegaly", "and cardiomegaly van", "cardiomegaly van bon", "van bon et al.", "bon et al. 2012", "al. 2012 harakalova", "2012 harakalova et", "harakalova et al. 2012", "et al. 2012 .", "atp binding cassette sub family", "binding cassette sub family c", "cassette sub family c 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"atria and reduces ventricular filling.", "and reduces ventricular filling. it", "reduces ventricular filling. it can", "ventricular filling. it can result", "filling. it can result in", "it can result in palpitations", "result in palpitations syncope", "palpitations syncope thromboembolic", "thromboembolic stroke and congestive", "stroke and congestive heart", "congestive heart failure olson", "heart failure olson et", "failure olson et al.", "olson et al. 2007 .", "et al. 2007 . defects", "al. 2007 . defects in", "2007 . defects in abcc9", "abcc9 can also cause hypertrichotic", "can also cause hypertrichotic osteochondrodysplasia", "cause hypertrichotic osteochondrodysplasia cantu", "hypertrichotic osteochondrodysplasia cantu syndrome", "mim:239850 a rare", "239850 a rare", "a rare disorder characterised by", "rare disorder characterised by congenital", "disorder characterised by congenital hypertrichosis", "by congenital hypertrichosis neonatal", "congenital hypertrichosis neonatal 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"collectins termed surfactant proteins", "surfactant proteins a b", "a b c", "b c and d", "c and d sftpa", "and d sftpa d", "d sftpa d .", "sftpa d . they influence", "d . they influence surfactant", ". they influence surfactant homeostasis", "influence surfactant homeostasis contributing", "surfactant homeostasis contributing to", "homeostasis contributing to the", "contributing to the physical structures", "to the physical structures of", "the physical structures of lipids", "physical structures of lipids in", "structures of lipids in the", "of lipids in the alveoli", "lipids in the alveoli and", "in the alveoli and to", "the alveoli and to the", "alveoli and to the regulation", "and to the regulation of", "to the regulation of surfactant", "the regulation of surfactant function", "regulation of surfactant function and", "of surfactant function and metabolism.", "surfactant function and metabolism. they", "function and metabolism. they are", "and metabolism. they are directly", "metabolism. they are directly secreted", "they are directly secreted from", "are directly secreted from alveolar", "directly secreted from alveolar type", "secreted from alveolar type ii", "from alveolar type ii cells", "alveolar type ii cells into", "type ii cells into the", "ii cells into the airway", "cells into the airway to", "into the airway to function", "the airway to function as", "airway to function as part", "to function as part of", "function as part of the", "as part of the surfactant.", "part of the surfactant. sftpa", "of the surfactant. sftpa and", "the surfactant. sftpa and d", "surfactant. sftpa and d are", "sftpa and d are large", "d are large hydrophilic", "are large hydrophilic proteins", "large hydrophilic proteins while", "hydrophilic proteins while sftpb and", "proteins while sftpb and c", "while sftpb and c are", "sftpb and c are small", "c are small very", "are small very hydrophobic", "small very hydrophobic proteins", "very hydrophobic proteins johansson", "hydrophobic proteins johansson et", "proteins johansson et al.", "johansson et al. 1994 .", "et al. 1994 . in", "al. 1994 . in addition", "1994 . in addition to", ". in addition to their", "in addition to their surfactant", "addition to their surfactant functions", "their surfactant functions sftpa", "surfactant functions sftpa and", "functions sftpa and d", "sftpa and d play important", "and d play important roles", "d play important roles in", "play important roles in innate", "important roles in innate host", "roles in innate host defense", "in innate host defense by", "innate host defense by binding", "host defense by binding and", "defense by binding and clearing", "by binding and clearing invading", "binding and clearing invading microbes", "and clearing invading microbes from", "clearing invading microbes from the", "invading microbes from the lung", "from the lung kingma", "the lung kingma &", "lung kingma & whitsett", "kingma & whitsett 2006 .", "& whitsett 2006 . nuclear", "whitsett 2006 . nuclear regulation", ". nuclear regulation transport", "regulation transport metabolism", "transport metabolism reutilisation", "metabolism reutilisation and degradation", "reutilisation and degradation of surfactant", "and degradation of surfactant are", "degradation of surfactant are described", "of surfactant are described here", "are described here ikegami", "described here ikegami 2006", "ikegami 2006 boggaram 2009", "boggaram 2009 whitsett et", "2009 whitsett et al.", "whitsett et al. 2010 .", "et al. 2010 . mutations", "al. 2010 . mutations in", "2010 . mutations in genes", ". mutations in genes involved", "mutations in genes involved in", "in genes involved in these", "genes involved in these processes", "involved in these processes can", "in these processes can result", "these processes can result in", "processes can result in respiratory", "can result in respiratory distress", "result in respiratory distress syndrome", "respiratory distress syndrome lung", "distress syndrome lung proteinosis", "lung proteinosis interstitial lung", "proteinosis interstitial lung diseases", "interstitial lung diseases and chronic", "lung diseases and chronic lung", "diseases and chronic lung diseases", "chronic lung diseases perez", "lung diseases perez gil", "diseases perez gil &", "perez gil & weaver 2010", "& weaver 2010 whitsett", "weaver 2010 whitsett et", "2010 whitsett et al.", "et al. 2010 akella", "al. 2010 akella &", "2010 akella & deshpande", "& deshpande 2013 jo", "deshpande 2013 jo 2014", "2013 jo 2014 ." ] }, { "record_id": "GLY_000594_1_1073", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5685938", "r hsa", "hsa 5685938", "r hsa 5685938" ] }, { "record_id": "GLY_000594_1_1073", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hdr through", "through single", "single strand", "strand annealing", "hdr through single", "through single strand", "single strand annealing", "annealing ssa", "hdr through single strand", "through single strand annealing", "strand annealing ssa", "hdr through single strand annealing", "single strand annealing ssa", "homology directed", "directed repair", "similar to", "to hdr", "through homologous", "homologous recombination", "recombination repair", "involves extensive", "extensive resection", "resection of", "of dna", "dna double", "double strand", "strand break", "break ends", "preceded by", "by atm", "atm activation", "activation and", "and formation", "formation of", "of the", "the so", "so called", "called ionizing", "ionizing radiation", "radiation induced", "induced foci", "at dna", "dna dsb", "dsb sites.", "sites. following", "following atm", "and foci", "foci formation", "the two", "two step", "step resection", "resection is", "is initiated", "initiated by", "by the", "the mrn", "mrn complex", "and rbbp8", "associated with", "with brca1:bard1", "and completed", "completed by", "by exo1", "exo1 or", "or dna2", "dna2 in", "in cooperation", "cooperation with", "with dna", "dna helicases", "helicases blm", "wrn and", "and brip1", "sartori et", "et al.", "al. 2007", "yun and", "and hiom", "hiom 2009", "eid et", "al. 2010", "nimonkar et", "al. 2011", "suhasini et", "sturzenegger et", "al. 2014", "2014 .", ". long", "long 3'", "3' ssdna", "ssdna overhangs", "overhangs produced", "produced by", "by extensive", "resection are", "are coated", "coated by", "the rpa", "rpa heterotrimer", "triggering atr", "atr signaling.", "signaling. atr", "atr signaling", "signaling is", "is needed", "needed for", "for ssa", "probably because", "because of", "the related", "related phosphorylation", "phosphorylation of", "of rpa2", "zou and", "and elledge", "elledge 2003", "anantha et", "liu et", "al. 2012", "2012 .

              rad52", ".

              rad52 is", "is the", "the key", "key mediator", "mediator of", "of ssa.", "ssa. activated", "activated atm", "atm phosphorylates", "phosphorylates and", "and activates", "activates abl1", "and activated", "activated abl1", "abl1 subsequently", "subsequently phosphorylates", "phosphorylates pre", "pre formed", "formed rad52", "rad52 heptameric", "heptameric rings", "increasing their", "their affinity", "affinity for", "for ssdna", "honda et", "2011 .", ". phosphorylated", "phosphorylated rad52", "rad52 binds", "binds phosphorylated", "phosphorylated rpa", "rpa heterotrimers", "heterotrimers on", "on 3'", "overhangs at", "at resected", "resected dna", "dna dsbs.", "dsbs. rad52", "rad52 also", "also binds", "binds rad51", "rad51 and", "and prevents", "prevents formation", "of invasive", "invasive rad51", "rad51 nucleofilaments", "nucleofilaments involved", "involved in", "in hrr", "chen et", "al. 1999", "van dyck", "dyck et", "parsons et", "al. 2000", "jackson et", "al. 2002", "singleton et", "2002 .

              rad52", ".

              rad52 promotes", "promotes annealing", "annealing of", "of two", "two 3'", "overhangs when", "when highly", "highly homologous", "homologous directed", "directed repeats", "repeats are", "are present", "present in", "in both", "both 3'", "ssdna overhangs.", "overhangs. nonhomologous", "nonhomologous regions", "regions lying", "lying 3'", "3' to", "to the", "the annealed", "annealed repeats", "are displaced", "displaced as", "as 3'", "3' flaps", "al. 2001", "stark et", "al. 2004", "mansour et", "al. 2008", "2008 .", ". the", "the endonuclease", "endonuclease complex", "complex composed", "composed of", "of ercc1", "ercc1 and", "and ercc4", "is subsequently", "subsequently recruited", "recruited to", "to ssa", "ssa sites", "sites through", "through direct", "direct interaction", "interaction between", "between rad52", "rad52 and", "leading to", "to cleavage", "cleavage of", "of 3'", "motycka et", "al minawi", "minawi et", "the identity", "identity of", "of a", "a dna", "dna ligase", "ligase that", "that closes", "closes the", "the remaining", "remaining single", "strand nicks", "to complete", "complete ssa", "ssa mediated", "mediated repair", "repair is", "is not", "not known.

              ssa", "known.

              ssa results", "results in", "in deletion", "deletion of", "of one", "one of", "repeats and", "and the", "the intervening", "intervening dna", "dna sequence", "sequence between", "between the", "two annealed", "and is", "is thus", "thus mutagenic.", "homology directed repair", "repair hdr", "similar to hdr", "to hdr through", "hdr through homologous", "through homologous recombination", "homologous recombination repair", "repair hrr", "involves extensive resection", "extensive resection of", "resection of dna", "of dna double", "dna double strand", "double strand break", "strand break ends", "ends dsbs", "preceded by atm", "by atm activation", "atm activation and", "activation and formation", "and formation of", "formation of the", "of the so", "the so called", "so called ionizing", "called ionizing radiation", "ionizing radiation induced", "radiation induced foci", "foci irif", "irif at", "at dna dsb", "dna dsb sites.", "dsb sites. following", "sites. following atm", "following atm activation", "activation and foci", "and foci formation", "formation the", "the two step", "two step resection", "step resection is", "resection is initiated", "is initiated by", "initiated by the", "by the mrn", "the mrn complex", "complex mre11a:rad50:nbn", "mre11a:rad50:nbn and", "rbbp8 ctip", "ctip associated", "associated with brca1:bard1", "brca1:bard1 and", "and completed by", "completed by exo1", "by exo1 or", "exo1 or dna2", "or dna2 in", "dna2 in cooperation", "in cooperation with", "cooperation with dna", "with dna helicases", "dna helicases blm", "blm wrn", "wrn and brip1", "brip1 bach1", "sartori et al.", "et al. 2007", "2007 yun", "yun and hiom", "and hiom 2009", "2009 eid", "eid et al.", "et al. 2010", "2010 nimonkar", "nimonkar et al.", "et al. 2011", "2011 suhasini", "suhasini et al.", "2011 sturzenegger", "sturzenegger et al.", "et al. 2014", "al. 2014 .", "2014 . long", ". long 3'", "long 3' ssdna", "3' ssdna overhangs", "ssdna overhangs produced", "overhangs produced by", "produced by extensive", "by extensive resection", "extensive resection are", "resection are coated", "are coated by", "coated by the", "by the rpa", "the rpa heterotrimer", "heterotrimer rpa1:rpa2:rpa3", "triggering atr signaling.", "atr signaling. atr", "signaling. atr signaling", "atr signaling is", "signaling is needed", "is needed for", "needed for ssa", "ssa probably", "probably because of", "because of the", "of the related", "the related phosphorylation", "related phosphorylation of", "phosphorylation of rpa2", "rpa2 zou", "zou and elledge", "and elledge 2003", "2003 anantha", "anantha et al.", "2007 liu", "liu et al.", "et al. 2012", "al. 2012 .

              rad52", "2012 .

              rad52 is", ".

              rad52 is the", "is the key", "the key mediator", "key mediator of", "mediator of ssa.", "of ssa. activated", "ssa. activated atm", "activated atm phosphorylates", "atm phosphorylates and", "phosphorylates and activates", "and activates abl1", "abl1 and", "and activated abl1", "activated abl1 subsequently", "abl1 subsequently phosphorylates", "subsequently phosphorylates pre", "phosphorylates pre formed", "pre formed rad52", "formed rad52 heptameric", "rad52 heptameric rings", "rings increasing", "increasing their affinity", "their affinity for", "affinity for ssdna", "ssdna honda", "honda et al.", "al. 2011 .", "2011 . phosphorylated", ". phosphorylated rad52", "phosphorylated rad52 binds", "rad52 binds phosphorylated", "binds phosphorylated rpa", "phosphorylated rpa heterotrimers", "rpa heterotrimers on", "heterotrimers on 3'", "on 3' ssdna", "ssdna overhangs at", "overhangs at resected", "at resected dna", "resected dna dsbs.", "dna dsbs. rad52", "dsbs. rad52 also", "rad52 also binds", "also binds rad51", "binds rad51 and", "rad51 and prevents", "and prevents formation", "prevents formation of", "formation of invasive", "of invasive rad51", "invasive rad51 nucleofilaments", "rad51 nucleofilaments involved", "nucleofilaments involved in", "involved in hrr", "hrr chen", "chen et al.", "et al. 1999", "1999 van", "van dyck et", "dyck et al.", "1999 parsons", "parsons et al.", "et al. 2000", "2000 jackson", "jackson et al.", "et al. 2002", "2002 singleton", "singleton et al.", "al. 2002 .

              rad52", "2002 .

              rad52 promotes", ".

              rad52 promotes annealing", "promotes annealing of", "annealing of two", "of two 3'", "two 3' ssdna", "ssdna overhangs when", "overhangs when highly", "when highly homologous", "highly homologous directed", "homologous directed repeats", "directed repeats are", "repeats are present", "are present in", "present in both", "in both 3'", "both 3' ssdna", "3' ssdna overhangs.", "ssdna overhangs. nonhomologous", "overhangs. nonhomologous regions", "nonhomologous regions lying", "regions lying 3'", "lying 3' to", "3' to the", "to the annealed", "the annealed repeats", "annealed repeats are", "repeats are displaced", "are displaced as", "displaced as 3'", "as 3' flaps", "flaps parsons", "2000 van", "et al. 2001", "2001 singleton", "2002 stark", "stark et al.", "et al. 2004", "2004 mansour", "mansour et al.", "et al. 2008", "al. 2008 .", "2008 . the", ". the endonuclease", "the endonuclease complex", "endonuclease complex composed", "complex composed of", "composed of ercc1", "of ercc1 and", "ercc1 and ercc4", "ercc4 xpf", "xpf is", "is subsequently recruited", "subsequently recruited to", "recruited to ssa", "to ssa sites", "ssa sites through", "sites through direct", "through direct interaction", "direct interaction between", "interaction between rad52", "between rad52 and", "rad52 and ercc4", "ercc4 leading", "leading to cleavage", "to cleavage of", "cleavage of 3'", "of 3' flaps", "flaps motycka", "motycka et al.", "2004 al", "al minawi et", "minawi et al.", ". the identity", "the identity of", "identity of a", "of a dna", "a dna ligase", "dna ligase that", "ligase that closes", "that closes the", "closes the remaining", "the remaining single", "remaining single strand", "single strand nicks", "nicks ssbs", "ssbs to", "to complete ssa", "complete ssa mediated", "ssa mediated repair", "mediated repair is", "repair is not", "is not known.

              ssa", "not known.

              ssa results", "known.

              ssa results in", "results in deletion", "in deletion of", "deletion of one", "of one of", "one of the", "of the annealed", "annealed repeats and", "repeats and the", "and the intervening", "the intervening dna", "intervening dna sequence", "dna sequence between", "sequence between the", "between the two", "the two annealed", "two annealed repeats", "repeats and is", "and is thus", "is thus mutagenic.", "directed repair hdr", "ssa similar", "similar to hdr through", "to hdr through homologous", "hdr through homologous recombination", "through homologous recombination repair", "recombination repair hrr", "hrr involves", "involves extensive resection of", "extensive resection of dna", "resection of dna double", "of dna double strand", "dna double strand break", "double strand break ends", "break ends dsbs", "dsbs preceded", "preceded by atm activation", "by atm activation and", "atm activation and formation", "activation and formation of", "and formation of the", "formation of the so", "of the so called", "the so called ionizing", "so called ionizing radiation", "called ionizing radiation induced", "ionizing radiation induced foci", "induced foci irif", "irif at dna", "at dna dsb sites.", "dna dsb sites. following", "dsb sites. following atm", "sites. following atm activation", "following atm activation and", "atm activation and foci", "activation and foci formation", "foci formation the", "formation the two", "the two step resection", "two step resection is", "step resection is initiated", "resection is initiated by", "is initiated by the", "initiated by the mrn", "by the mrn complex", "mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn and rbbp8", "and rbbp8 ctip", "ctip associated with", "with brca1:bard1 and", "brca1:bard1 and completed", "and completed by exo1", "completed by exo1 or", "by exo1 or dna2", "exo1 or dna2 in", "or dna2 in cooperation", "dna2 in cooperation with", "in cooperation with dna", "cooperation with dna helicases", "with dna helicases blm", "helicases blm wrn", "blm wrn and", "and brip1 bach1", "bach1 sartori", "sartori et al. 2007", "al. 2007 yun", "2007 yun and", "yun and hiom 2009", "hiom 2009 eid", "2009 eid et", "eid et al. 2010", "al. 2010 nimonkar", "2010 nimonkar et", "nimonkar et al. 2011", "al. 2011 suhasini", "2011 suhasini et", "suhasini et al. 2011", "al. 2011 sturzenegger", "2011 sturzenegger et", "sturzenegger et al. 2014", "et al. 2014 .", "al. 2014 . long", "2014 . long 3'", ". long 3' ssdna", "long 3' ssdna overhangs", "3' ssdna overhangs produced", "ssdna overhangs produced by", "overhangs produced by extensive", "produced by extensive resection", "by extensive resection are", "extensive resection are coated", "resection are coated by", "are coated by the", "coated by the rpa", "by the rpa heterotrimer", "rpa heterotrimer rpa1:rpa2:rpa3", "rpa1:rpa2:rpa3 triggering", "triggering atr signaling. atr", "atr signaling. atr signaling", "signaling. atr signaling is", "atr signaling is needed", "signaling is needed for", "is needed for ssa", "for ssa probably", "ssa probably because", "probably because of the", "because of the related", "of the related phosphorylation", "the related phosphorylation of", "related phosphorylation of rpa2", "of rpa2 zou", "rpa2 zou and", "zou and elledge 2003", "elledge 2003 anantha", "2003 anantha et", "anantha et al. 2007", "al. 2007 liu", "2007 liu et", "liu et al. 2012", "et al. 2012 .

              rad52", "al. 2012 .

              rad52 is", "2012 .

              rad52 is the", ".

              rad52 is the key", "is the key mediator", "the key mediator of", "key mediator of ssa.", "mediator of ssa. activated", "of ssa. activated atm", "ssa. activated atm phosphorylates", "activated atm phosphorylates and", "atm phosphorylates and activates", "phosphorylates and activates abl1", "activates abl1 and", "abl1 and activated", "and activated abl1 subsequently", "activated abl1 subsequently phosphorylates", "abl1 subsequently phosphorylates pre", "subsequently phosphorylates pre formed", "phosphorylates pre formed rad52", "pre formed rad52 heptameric", "formed rad52 heptameric rings", "heptameric rings increasing", "rings increasing their", "increasing their affinity for", "their affinity for ssdna", "for ssdna honda", "ssdna honda et", "honda et al. 2011", "et al. 2011 .", "al. 2011 . phosphorylated", "2011 . phosphorylated rad52", ". phosphorylated rad52 binds", "phosphorylated rad52 binds phosphorylated", "rad52 binds phosphorylated rpa", "binds phosphorylated rpa heterotrimers", "phosphorylated rpa heterotrimers on", "rpa heterotrimers on 3'", "heterotrimers on 3' ssdna", "on 3' ssdna overhangs", "3' ssdna overhangs at", "ssdna overhangs at resected", "overhangs at resected dna", "at resected dna dsbs.", "resected dna dsbs. rad52", "dna dsbs. rad52 also", "dsbs. rad52 also binds", "rad52 also binds rad51", "also binds rad51 and", "binds rad51 and prevents", "rad51 and prevents formation", "and prevents formation of", "prevents formation of invasive", "formation of invasive rad51", "of invasive rad51 nucleofilaments", "invasive rad51 nucleofilaments involved", "rad51 nucleofilaments involved in", "nucleofilaments involved in hrr", "in hrr chen", "hrr chen et", "chen et al. 1999", "al. 1999 van", "1999 van dyck", "van dyck et al.", "dyck et al. 1999", "al. 1999 parsons", "1999 parsons et", "parsons et al. 2000", "al. 2000 jackson", "2000 jackson et", "jackson et al. 2002", "al. 2002 singleton", "2002 singleton et", "singleton et al. 2002", "et al. 2002 .

              rad52", "al. 2002 .

              rad52 promotes", "2002 .

              rad52 promotes annealing", ".

              rad52 promotes annealing of", "promotes annealing of two", "annealing of two 3'", "of two 3' ssdna", "two 3' ssdna overhangs", "3' ssdna overhangs when", "ssdna overhangs when highly", "overhangs when highly homologous", "when highly homologous directed", "highly homologous directed repeats", "homologous directed repeats are", "directed repeats are present", "repeats are present in", "are present in both", "present in both 3'", "in both 3' ssdna", "both 3' ssdna overhangs.", "3' ssdna overhangs. nonhomologous", "ssdna overhangs. nonhomologous regions", "overhangs. nonhomologous regions lying", "nonhomologous regions lying 3'", "regions lying 3' to", "lying 3' to the", "3' to the annealed", "to the annealed repeats", "the annealed repeats are", "annealed repeats are displaced", "repeats are displaced as", "are displaced as 3'", "displaced as 3' flaps", "3' flaps parsons", "flaps parsons et", "al. 2000 van", "2000 van dyck", "dyck et al. 2001", "al. 2001 singleton", "2001 singleton et", "al. 2002 stark", "2002 stark et", "stark et al. 2004", "al. 2004 mansour", "2004 mansour et", "mansour et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the endonuclease", ". the endonuclease complex", "the endonuclease complex composed", "endonuclease complex composed of", "complex composed of ercc1", "composed of ercc1 and", "of ercc1 and ercc4", "and ercc4 xpf", "xpf is subsequently", "is subsequently recruited to", "subsequently recruited to ssa", "recruited to ssa sites", "to ssa sites through", "ssa sites through direct", "sites through direct interaction", "through direct interaction between", "direct interaction between rad52", "interaction between rad52 and", "between rad52 and ercc4", "and ercc4 leading", "ercc4 leading to", "leading to cleavage of", "to cleavage of 3'", "cleavage of 3' flaps", "3' flaps motycka", "flaps motycka et", "motycka et al. 2004", "al. 2004 al", "2004 al minawi", "al minawi et al.", "minawi et al. 2008", "2008 . the identity", ". the identity of", "the identity of a", "identity of a dna", "of a dna ligase", "a dna ligase that", "dna ligase that closes", "ligase that closes the", "that closes the remaining", "closes the remaining single", "the remaining single strand", "remaining single strand nicks", "strand nicks ssbs", "ssbs to complete", "to complete ssa mediated", "complete ssa mediated repair", "ssa mediated repair is", "mediated repair is not", "repair is not known.

              ssa", "is not known.

              ssa results", "not known.

              ssa results in", "known.

              ssa results in deletion", "results in deletion of", "in deletion of one", "deletion of one of", "of one of the", "one of the annealed", "of the annealed repeats", "the annealed repeats and", "annealed repeats and the", "repeats and the intervening", "and the intervening dna", "the intervening dna sequence", "intervening dna sequence between", "dna sequence between the", "sequence between the two", "between the two annealed", "the two annealed repeats", "two annealed repeats and", "annealed repeats and is", "repeats and is thus", "and is thus mutagenic.", "homology directed repair hdr", "repair hdr through", "ssa similar to", "similar to hdr through homologous", "to hdr through homologous recombination", "hdr through homologous recombination repair", "homologous recombination repair hrr", "hrr involves extensive", "involves extensive resection of dna", "extensive resection of dna double", "resection of dna double strand", "of dna double strand break", "dna double strand break ends", "strand break ends dsbs", "dsbs preceded by", "preceded by atm activation and", "by atm activation and formation", "atm activation and formation of", "activation and formation of the", "and formation of the so", "formation of the so called", "of the so called ionizing", "the so called ionizing radiation", "so called ionizing radiation induced", "called ionizing radiation induced foci", "radiation induced foci irif", "foci irif at", "irif at dna dsb", "at dna dsb sites. following", "dna dsb sites. following atm", "dsb sites. following atm activation", "sites. following atm activation and", "following atm activation and foci", "atm activation and foci formation", "and foci formation the", "foci formation the two", "formation the two step", "the two step resection is", "two step resection is initiated", "step resection is initiated by", "resection is initiated by the", "is initiated by the mrn", "initiated by the mrn complex", "the mrn complex mre11a:rad50:nbn", "complex mre11a:rad50:nbn and", "rbbp8 ctip associated", "ctip associated with brca1:bard1", "associated with brca1:bard1 and", "with brca1:bard1 and completed", "brca1:bard1 and completed by", "and completed by exo1 or", "completed by exo1 or dna2", "by exo1 or dna2 in", "exo1 or dna2 in cooperation", "or dna2 in cooperation with", "dna2 in cooperation with dna", "in cooperation with dna helicases", "cooperation with dna helicases blm", "dna helicases blm wrn", "helicases blm wrn and", "blm wrn and brip1", "wrn and brip1 bach1", "bach1 sartori et", "et al. 2007 yun", "al. 2007 yun and", "2007 yun and hiom", "and hiom 2009 eid", "hiom 2009 eid et", "2009 eid et al.", "et al. 2010 nimonkar", "al. 2010 nimonkar et", "2010 nimonkar et al.", "et al. 2011 suhasini", "al. 2011 suhasini et", "2011 suhasini et al.", "et al. 2011 sturzenegger", "al. 2011 sturzenegger et", "2011 sturzenegger et al.", "sturzenegger et al. 2014 .", "et al. 2014 . long", "al. 2014 . long 3'", "2014 . long 3' ssdna", ". long 3' ssdna overhangs", "long 3' ssdna overhangs produced", "3' ssdna overhangs produced by", "ssdna overhangs produced by extensive", "overhangs produced by extensive resection", "produced by extensive resection are", "by extensive resection are coated", "extensive resection are coated by", "resection are coated by the", "are coated by the rpa", "coated by the rpa heterotrimer", "the rpa heterotrimer rpa1:rpa2:rpa3", "rpa1:rpa2:rpa3 triggering atr", "triggering atr signaling. atr signaling", "atr signaling. atr signaling is", "signaling. atr signaling is needed", "atr signaling is needed for", "signaling is needed for ssa", "needed for ssa probably", "for ssa probably because", "ssa probably because of", "probably because of the related", "because of the related phosphorylation", "of the related phosphorylation of", "the related phosphorylation of rpa2", "phosphorylation of rpa2 zou", "of rpa2 zou and", "rpa2 zou and elledge", "and elledge 2003 anantha", "elledge 2003 anantha et", "2003 anantha et al.", "et al. 2007 liu", "al. 2007 liu et", "2007 liu et al.", "liu et al. 2012 .

              rad52", "et al. 2012 .

              rad52 is", "al. 2012 .

              rad52 is the", "2012 .

              rad52 is the key", ".

              rad52 is the key mediator", "is the key mediator of", "the key mediator of ssa.", "key mediator of ssa. activated", "mediator of ssa. activated atm", "of ssa. activated atm phosphorylates", "ssa. activated atm phosphorylates and", "activated atm phosphorylates and activates", "atm phosphorylates and activates abl1", "and activates abl1 and", "activates abl1 and activated", "abl1 and activated abl1", "and activated abl1 subsequently phosphorylates", "activated abl1 subsequently phosphorylates pre", "abl1 subsequently phosphorylates pre formed", "subsequently phosphorylates pre formed rad52", "phosphorylates pre formed rad52 heptameric", "pre formed rad52 heptameric rings", "rad52 heptameric rings increasing", "heptameric rings increasing their", "rings increasing their affinity", "increasing their affinity for ssdna", "affinity for ssdna honda", "for ssdna honda et", "ssdna honda et al.", "honda et al. 2011 .", "et al. 2011 . phosphorylated", "al. 2011 . phosphorylated rad52", "2011 . phosphorylated rad52 binds", ". phosphorylated rad52 binds phosphorylated", "phosphorylated rad52 binds phosphorylated rpa", "rad52 binds phosphorylated rpa heterotrimers", "binds phosphorylated rpa heterotrimers on", "phosphorylated rpa heterotrimers on 3'", "rpa heterotrimers on 3' ssdna", "heterotrimers on 3' ssdna overhangs", "on 3' ssdna overhangs at", "3' ssdna overhangs at resected", "ssdna overhangs at resected dna", "overhangs at resected dna dsbs.", "at resected dna dsbs. rad52", "resected dna dsbs. rad52 also", "dna dsbs. rad52 also binds", "dsbs. rad52 also binds rad51", "rad52 also binds rad51 and", "also binds rad51 and prevents", "binds rad51 and prevents formation", "rad51 and prevents formation of", "and prevents formation of invasive", "prevents formation of invasive rad51", "formation of invasive rad51 nucleofilaments", "of invasive rad51 nucleofilaments involved", "invasive rad51 nucleofilaments involved in", "rad51 nucleofilaments involved in hrr", "involved in hrr chen", "in hrr chen et", "hrr chen et al.", "et al. 1999 van", "al. 1999 van dyck", "1999 van dyck et", "van dyck et al. 1999", "et al. 1999 parsons", "al. 1999 parsons et", "1999 parsons et al.", "et al. 2000 jackson", "al. 2000 jackson et", "2000 jackson et al.", "et al. 2002 singleton", "al. 2002 singleton et", "2002 singleton et al.", "singleton et al. 2002 .

              rad52", "et al. 2002 .

              rad52 promotes", "al. 2002 .

              rad52 promotes annealing", "2002 .

              rad52 promotes annealing of", ".

              rad52 promotes annealing of two", "promotes annealing of two 3'", "annealing of two 3' ssdna", "of two 3' ssdna overhangs", "two 3' ssdna overhangs when", "3' ssdna overhangs when highly", "ssdna overhangs when highly homologous", "overhangs when highly homologous directed", "when highly homologous directed repeats", "highly homologous directed repeats are", "homologous directed repeats are present", "directed repeats are present in", "repeats are present in both", "are present in both 3'", "present in both 3' ssdna", "in both 3' ssdna overhangs.", "both 3' ssdna overhangs. nonhomologous", "3' ssdna overhangs. nonhomologous regions", "ssdna overhangs. nonhomologous regions lying", "overhangs. nonhomologous regions lying 3'", "nonhomologous regions lying 3' to", "regions lying 3' to the", "lying 3' to the annealed", "3' to the annealed repeats", "to the annealed repeats are", "the annealed repeats are displaced", "annealed repeats are displaced as", "repeats are displaced as 3'", "are displaced as 3' flaps", "as 3' flaps parsons", "3' flaps parsons et", "flaps parsons et al.", "et al. 2000 van", "al. 2000 van dyck", "2000 van dyck et", "van dyck et al. 2001", "et al. 2001 singleton", "al. 2001 singleton et", "2001 singleton et al.", "et al. 2002 stark", "al. 2002 stark et", "2002 stark et al.", "et al. 2004 mansour", "al. 2004 mansour et", "2004 mansour et al.", "mansour et al. 2008 .", "et al. 2008 . the", "al. 2008 . the endonuclease", "2008 . the endonuclease complex", ". the endonuclease complex composed", "the endonuclease complex composed of", "endonuclease complex composed of ercc1", "complex composed of ercc1 and", "composed of ercc1 and ercc4", "ercc1 and ercc4 xpf", "ercc4 xpf is", "xpf is subsequently recruited", "is subsequently recruited to ssa", "subsequently recruited to ssa sites", "recruited to ssa sites through", "to ssa sites through direct", "ssa sites through direct interaction", "sites through direct interaction between", "through direct interaction between rad52", "direct interaction between rad52 and", "interaction between rad52 and ercc4", "rad52 and ercc4 leading", "and ercc4 leading to", "ercc4 leading to cleavage", "leading to cleavage of 3'", "to cleavage of 3' flaps", "of 3' flaps motycka", "3' flaps motycka et", "flaps motycka et al.", "et al. 2004 al", "al. 2004 al minawi", "2004 al minawi et", "al minawi et al. 2008", "minawi et al. 2008 .", "al. 2008 . the identity", "2008 . the identity of", ". the identity of a", "the identity of a dna", "identity of a dna ligase", "of a dna ligase that", "a dna ligase that closes", "dna ligase that closes the", "ligase that closes the remaining", "that closes the remaining single", "closes the remaining single strand", "the remaining single strand nicks", "single strand nicks ssbs", "nicks ssbs to", "ssbs to complete ssa", "to complete ssa mediated repair", "complete ssa mediated repair is", "ssa mediated repair is not", "mediated repair is not known.

              ssa", "repair is not known.

              ssa results", "is not known.

              ssa results in", "not known.

              ssa results in deletion", "known.

              ssa results in deletion of", "results in deletion of one", "in deletion of one of", "deletion of one of the", "of one of the annealed", "one of the annealed repeats", "of the annealed repeats and", "the annealed repeats and the", "annealed repeats and the intervening", "repeats and the intervening dna", "and the intervening dna sequence", "the intervening dna sequence between", "intervening dna sequence between the", "dna sequence between the two", "sequence between the two annealed", "between the two annealed repeats", "the two annealed repeats and", "two annealed repeats and is", "annealed repeats and is thus", "repeats and is thus mutagenic." ] }, { "record_id": "GLY_000594_1_1074", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5685939", "r hsa", "hsa 5685939", "r hsa 5685939" ] }, { "record_id": "GLY_000594_1_1074", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hdr through", "through mmej", "alt nhej", "hdr through mmej", "mmej alt", "through mmej alt", "mmej alt nhej", "hdr through mmej alt", "through mmej alt nhej", "homology directed", "directed repair", "through microhomology", "microhomology mediated", "mediated end", "end joining", "is an", "an error", "error prone", "prone process", "process also", "also known", "known as", "as alternative", "alternative nonhomologous", "nonhomologous end", "although it", "it does", "does not", "not involve", "involve proteins", "proteins that", "that participate", "participate in", "in the", "the classical", "classical nhej.", "nhej. contrary", "contrary to", "to the", "classical nhej", "nhej and", "and other", "other hdr", "hdr pathways", "homologous recombination", "recombination repair", "and single", "single strand", "strand annealing", "mmej does", "not require", "require atm", "atm activation.", "activation. in", "in fact", "atm activation", "activation inhibits", "inhibits mmej.", "mmej. therefore", "mmej may", "may be", "be triggered", "triggered when", "when the", "the amount", "amount of", "of dna", "dna double", "double strand", "strand breaks", "overwhelms dna", "dna repair", "repair machinery", "machinery of", "of higher", "higher fidelity", "fidelity or", "or when", "when cells", "cells are", "are deficient", "deficient in", "in components", "components of", "of high", "high fidelity", "fidelity dna", "dna repair.

              mmej", "repair.

              mmej is", "is initiated", "initiated by", "by a", "a limited", "limited resection", "resection of", "dna dsb", "dsb ends", "ends by", "by the", "the mrn", "mrn complex", "and rbbp8", "the absence", "absence of", "of cdk2", "cdk2 mediated", "mediated rbbp8", "rbbp8 phosphorylation", "phosphorylation and", "and related", "related brca1:bard1", "brca1:bard1 recruitment", "yun and", "and hiom", "hiom 2009", "2009 .", ". single", "strand dna", "at resected", "resected dna", "ends recruits", "recruits parp1", "parp1 or", "or parp2", "parp2 homo", "or heterodimers", "together with", "with dna", "dna polymerase", "polymerase theta", "and fen1", "fen1 5'", "5' flap", "flap endonuclease.", "endonuclease. in", "in a", "a poorly", "poorly studied", "studied sequence", "sequence of", "of events", "polq promotes", "promotes the", "the annealing", "annealing of", "of two", "two 3'", "3' ssdna", "ssdna overhangs", "overhangs through", "through microhomologous", "microhomologous regions", "regions that", "that are", "are optimally", "optimally 10", "10 19", "19 nucleotides", "nucleotides long.", "long. using", "using analogy", "analogy with", "with polb", "polb mediated", "mediated long", "long patch", "patch base", "base excision", "excision repair", "it is", "is plausible", "plausible that", "that parp1", "dimers coordinate", "coordinate the", "the extension", "extension of", "of annealed", "annealed 3'", "overhangs via", "via polq", "polq mediated", "mediated strand", "strand displacement", "displacement synthesis", "synthesis with", "with fen1", "fen1 mediated", "mediated cleavage", "cleavage of", "of the", "the resulting", "resulting 5'", "5' flaps", "liang et", "et al.", "al. 2005", "mansour et", "al. 2011", "sharma et", "al. 2015", "kent et", "ciccaldi et", "mateos gomez", "gomez et", "2015 .", ". the", "complex subsequently", "subsequently recruits", "recruits dna", "dna ligase", "ligase 3", "bound to", "to xrcc1", "to ligate", "ligate the", "the remaining", "remaining single", "strand nicks", "at mmej", "mmej sites", "della maria", "maria et", "2011 .

              similar", ".

              similar to", "to single", "mmej leads", "leads to", "to deletion", "deletion of", "of one", "one of", "the microhomology", "microhomology regions", "regions used", "used for", "for annealing", "annealing and", "and the", "the dna", "dna sequence", "sequence in", "in between", "between two", "two annealed", "annealed microhomology", "microhomology regions.", "regions. mmej", "just like", "like classical", "can result", "result in", "in genomic", "genomic translocations", "ghezraoui et", "al. 2014", "2014 .", ". in", "in addition", "since polq", "polq is", "prone dna", "mmej introduces", "introduces frequent", "frequent base", "base substitutions", "ceccaldi et", "homology directed repair", "repair hdr", "through microhomology mediated", "microhomology mediated end", "mediated end joining", "joining mmej", "mmej is", "is an error", "an error prone", "error prone process", "prone process also", "process also known", "also known as", "known as alternative", "as alternative nonhomologous", "alternative nonhomologous end", "nonhomologous end joining", "joining alt", "although it does", "it does not", "does not involve", "not involve proteins", "involve proteins that", "proteins that participate", "that participate in", "participate in the", "in the classical", "the classical nhej.", "classical nhej. contrary", "nhej. contrary to", "contrary to the", "to the classical", "the classical nhej", "classical nhej and", "nhej and other", "and other hdr", "other hdr pathways", "pathways homologous", "homologous recombination repair", "repair hrr", "hrr and", "and single strand", "single strand annealing", "annealing ssa", "mmej does not", "does not require", "not require atm", "require atm activation.", "atm activation. in", "activation. in fact", "fact atm", "atm activation inhibits", "activation inhibits mmej.", "inhibits mmej. therefore", "therefore mmej", "mmej may be", "may be triggered", "be triggered when", "triggered when the", "when the amount", "the amount of", "amount of dna", "of dna double", "dna double strand", "double strand breaks", "breaks dsbs", "dsbs overwhelms", "overwhelms dna repair", "dna repair machinery", "repair machinery of", "machinery of higher", "of higher fidelity", "higher fidelity or", "fidelity or when", "or when cells", "when cells are", "cells are deficient", "are deficient in", "deficient in components", "in components of", "components of high", "of high fidelity", "high fidelity dna", "fidelity dna repair.

              mmej", "dna repair.

              mmej is", "repair.

              mmej is initiated", "is initiated by", "initiated by a", "by a limited", "a limited resection", "limited resection of", "resection of dna", "of dna dsb", "dna dsb ends", "dsb ends by", "ends by the", "by the mrn", "the mrn complex", "complex mre11a:rad50:nbn", "mre11a:rad50:nbn and", "rbbp8 ctip", "in the absence", "the absence of", "absence of cdk2", "of cdk2 mediated", "cdk2 mediated rbbp8", "mediated rbbp8 phosphorylation", "rbbp8 phosphorylation and", "phosphorylation and related", "and related brca1:bard1", "related brca1:bard1 recruitment", "recruitment yun", "yun and hiom", "and hiom 2009", "hiom 2009 .", "2009 . single", ". single strand", "single strand dna", "dna ssdna", "ssdna at", "at resected dna", "resected dna dsb", "dsb ends recruits", "ends recruits parp1", "recruits parp1 or", "parp1 or parp2", "or parp2 homo", "homo or", "heterodimers together", "together with dna", "with dna polymerase", "dna polymerase theta", "theta polq", "polq and", "and fen1 5'", "fen1 5' flap", "5' flap endonuclease.", "flap endonuclease. in", "endonuclease. in a", "in a poorly", "a poorly studied", "poorly studied sequence", "studied sequence of", "sequence of events", "events polq", "polq promotes the", "promotes the annealing", "the annealing of", "annealing of two", "of two 3'", "two 3' ssdna", "3' ssdna overhangs", "ssdna overhangs through", "overhangs through microhomologous", "through microhomologous regions", "microhomologous regions that", "regions that are", "that are optimally", "are optimally 10", "optimally 10 19", "10 19 nucleotides", "19 nucleotides long.", "nucleotides long. using", "long. using analogy", "using analogy with", "analogy with polb", "with polb mediated", "polb mediated long", "mediated long patch", "long patch base", "patch base excision", "base excision repair", "repair ber", "it is plausible", "is plausible that", "plausible that parp1", "parp2 dimers", "dimers coordinate the", "coordinate the extension", "the extension of", "extension of annealed", "of annealed 3'", "annealed 3' ssdna", "ssdna overhangs via", "overhangs via polq", "via polq mediated", "polq mediated strand", "mediated strand displacement", "strand displacement synthesis", "displacement synthesis with", "synthesis with fen1", "with fen1 mediated", "fen1 mediated cleavage", "mediated cleavage of", "cleavage of the", "of the resulting", "the resulting 5'", "resulting 5' flaps", "flaps liang", "liang et al.", "et al. 2005", "2005 mansour", "mansour et al.", "et al. 2011", "2011 sharma", "sharma et al.", "et al. 2015", "2015 kent", "kent et al.", "2015 ciccaldi", "ciccaldi et al.", "2015 mateos", "mateos gomez et", "gomez et al.", "al. 2015 .", "2015 . the", ". the mrn", "mrn complex subsequently", "complex subsequently recruits", "subsequently recruits dna", "recruits dna ligase", "dna ligase 3", "3 lig3", "lig3 bound", "bound to xrcc1", "xrcc1 lig3:xrcc1", "lig3:xrcc1 to", "to ligate the", "ligate the remaining", "the remaining single", "remaining single strand", "single strand nicks", "nicks ssbs", "ssbs at", "at mmej sites", "sites della", "della maria et", "maria et al.", "al. 2011 .

              similar", "2011 .

              similar to", ".

              similar to single", "to single strand", "mmej leads to", "leads to deletion", "to deletion of", "deletion of one", "of one of", "one of the", "of the microhomology", "the microhomology regions", "microhomology regions used", "regions used for", "used for annealing", "for annealing and", "annealing and the", "and the dna", "the dna sequence", "dna sequence in", "sequence in between", "in between two", "between two annealed", "two annealed microhomology", "annealed microhomology regions.", "microhomology regions. mmej", "mmej just", "just like classical", "like classical nhej", "nhej can", "can result in", "result in genomic", "in genomic translocations", "translocations ghezraoui", "ghezraoui et al.", "et al. 2014", "al. 2014 .", "2014 . in", ". in addition", "addition since", "since polq is", "polq is an", "error prone dna", "prone dna polymerase", "polymerase mmej", "mmej introduces frequent", "introduces frequent base", "frequent base substitutions", "substitutions ceccaldi", "ceccaldi et al.", "directed repair hdr", "hdr through microhomology", "through microhomology mediated end", "microhomology mediated end joining", "end joining mmej", "mmej is an", "is an error prone", "an error prone process", "error prone process also", "prone process also known", "process also known as", "also known as alternative", "known as alternative nonhomologous", "as alternative nonhomologous end", "alternative nonhomologous end joining", "end joining alt", "joining alt nhej", "nhej although", "although it does not", "it does not involve", "does not involve proteins", "not involve proteins that", "involve proteins that participate", "proteins that participate in", "that participate in the", "participate in the classical", "in the classical nhej.", "the classical nhej. contrary", "classical nhej. contrary to", "nhej. contrary to the", "contrary to the classical", "to the classical nhej", "the classical nhej and", "classical nhej and other", "nhej and other hdr", "and other hdr pathways", "hdr pathways homologous", "pathways homologous recombination", "recombination repair hrr", "hrr and single", "and single strand annealing", "strand annealing ssa", "ssa mmej", "mmej does not require", "does not require atm", "not require atm activation.", "require atm activation. in", "atm activation. in fact", "in fact atm", "fact atm activation", "atm activation inhibits mmej.", "activation inhibits mmej. therefore", "mmej. therefore mmej", "therefore mmej may", "mmej may be triggered", "may be triggered when", "be triggered when the", "triggered when the amount", "when the amount of", "the amount of dna", "amount of dna double", "of dna double strand", "dna double strand breaks", "strand breaks dsbs", "dsbs overwhelms dna", "overwhelms dna repair machinery", "dna repair machinery of", "repair machinery of higher", "machinery of higher fidelity", "of higher fidelity or", "higher fidelity or when", "fidelity or when cells", "or when cells are", "when cells are deficient", "cells are deficient in", "are deficient in components", "deficient in components of", "in components of high", "components of high fidelity", "of high fidelity dna", "high fidelity dna repair.

              mmej", "fidelity dna repair.

              mmej is", "dna repair.

              mmej is initiated", "repair.

              mmej is initiated by", "is initiated by a", "initiated by a limited", "by a limited resection", "a limited resection of", "limited resection of dna", "resection of dna dsb", "of dna dsb ends", "dna dsb ends by", "dsb ends by the", "ends by the mrn", "by the mrn complex", "mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn and rbbp8", "and rbbp8 ctip", "ctip in", "in the absence of", "the absence of cdk2", "absence of cdk2 mediated", "of cdk2 mediated rbbp8", "cdk2 mediated rbbp8 phosphorylation", "mediated rbbp8 phosphorylation and", "rbbp8 phosphorylation and related", "phosphorylation and related brca1:bard1", "and related brca1:bard1 recruitment", "brca1:bard1 recruitment yun", "recruitment yun and", "yun and hiom 2009", "and hiom 2009 .", "hiom 2009 . single", "2009 . single strand", ". single strand dna", "strand dna ssdna", "ssdna at resected", "at resected dna dsb", "resected dna dsb ends", "dna dsb ends recruits", "dsb ends recruits parp1", "ends recruits parp1 or", "recruits parp1 or parp2", "parp1 or parp2 homo", "parp2 homo or", "homo or heterodimers", "or heterodimers together", "heterodimers together with", "together with dna polymerase", "with dna polymerase theta", "polymerase theta polq", "polq and fen1", "and fen1 5' flap", "fen1 5' flap endonuclease.", "5' flap endonuclease. in", "flap endonuclease. in a", "endonuclease. in a poorly", "in a poorly studied", "a poorly studied sequence", "poorly studied sequence of", "studied sequence of events", "of events polq", "events polq promotes", "polq promotes the annealing", "promotes the annealing of", "the annealing of two", "annealing of two 3'", "of two 3' ssdna", "two 3' ssdna overhangs", "3' ssdna overhangs through", "ssdna overhangs through microhomologous", "overhangs through microhomologous regions", "through microhomologous regions that", "microhomologous regions that are", "regions that are optimally", "that are optimally 10", "are optimally 10 19", "optimally 10 19 nucleotides", "10 19 nucleotides long.", "19 nucleotides long. using", "nucleotides long. using analogy", "long. using analogy with", "using analogy with polb", "analogy with polb mediated", "with polb mediated long", "polb mediated long patch", "mediated long patch base", "long patch base excision", "patch base excision repair", "excision repair ber", "ber it", "it is plausible that", "is plausible that parp1", "that parp1 or", "or parp2 dimers", "parp2 dimers coordinate", "dimers coordinate the extension", "coordinate the extension of", "the extension of annealed", "extension of annealed 3'", "of annealed 3' ssdna", "annealed 3' ssdna overhangs", "3' ssdna overhangs via", "ssdna overhangs via polq", "overhangs via polq mediated", "via polq mediated strand", "polq mediated strand displacement", "mediated strand displacement synthesis", "strand displacement synthesis with", "displacement synthesis with fen1", "synthesis with fen1 mediated", "with fen1 mediated cleavage", "fen1 mediated cleavage of", "mediated cleavage of the", "cleavage of the resulting", "of the resulting 5'", "the resulting 5' flaps", "5' flaps liang", "flaps liang et", "liang et al. 2005", "al. 2005 mansour", "2005 mansour et", "mansour et al. 2011", "al. 2011 sharma", "2011 sharma et", "sharma et al. 2015", "al. 2015 kent", "2015 kent et", "kent et al. 2015", "al. 2015 ciccaldi", "2015 ciccaldi et", "ciccaldi et al. 2015", "al. 2015 mateos", "2015 mateos gomez", "mateos gomez et al.", "gomez et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the mrn", ". the mrn complex", "the mrn complex subsequently", "mrn complex subsequently recruits", "complex subsequently recruits dna", "subsequently recruits dna ligase", "recruits dna ligase 3", "ligase 3 lig3", "lig3 bound to", "to xrcc1 lig3:xrcc1", "lig3:xrcc1 to ligate", "to ligate the remaining", "ligate the remaining single", "the remaining single strand", "remaining single strand nicks", "strand nicks ssbs", "ssbs at mmej", "mmej sites della", "sites della maria", "della maria et al.", "maria et al. 2011", "et al. 2011 .

              similar", "al. 2011 .

              similar to", "2011 .

              similar to single", ".

              similar to single strand", "to single strand annealing", "mmej leads to deletion", "leads to deletion of", "to deletion of one", "deletion of one of", "of one of the", "one of the microhomology", "of the microhomology regions", "the microhomology regions used", "microhomology regions used for", "regions used for annealing", "used for annealing and", "for annealing and the", "annealing and the dna", "and the dna sequence", "the dna sequence in", "dna sequence in between", "sequence in between two", "in between two annealed", "between two annealed microhomology", "two annealed microhomology regions.", "annealed microhomology regions. mmej", "regions. mmej just", "mmej just like", "just like classical nhej", "classical nhej can", "nhej can result", "can result in genomic", "result in genomic translocations", "genomic translocations ghezraoui", "translocations ghezraoui et", "ghezraoui et al. 2014", "et al. 2014 .", "al. 2014 . in", "2014 . in addition", "in addition since", "addition since polq", "since polq is an", "polq is an error", "an error prone dna", "error prone dna polymerase", "dna polymerase mmej", "polymerase mmej introduces", "mmej introduces frequent base", "introduces frequent base substitutions", "base substitutions ceccaldi", "substitutions ceccaldi et", "ceccaldi et al. 2015", "homology directed repair hdr", "repair hdr through", "hdr through microhomology mediated", "through microhomology mediated end joining", "mediated end joining mmej", "joining mmej is", "mmej is an error", "is an error prone process", "an error prone process also", "error prone process also known", "prone process also known as", "process also known as alternative", "also known as alternative nonhomologous", "known as alternative nonhomologous end", "as alternative nonhomologous end joining", "nonhomologous end joining alt", "end joining alt nhej", "alt nhej although", "nhej although it", "although it does not involve", "it does not involve proteins", "does not involve proteins that", "not involve proteins that participate", "involve proteins that participate in", "proteins that participate in the", "that participate in the classical", "participate in the classical nhej.", "in the classical nhej. contrary", "the classical nhej. contrary to", "classical nhej. contrary to the", "nhej. contrary to the classical", "contrary to the classical nhej", "to the classical nhej and", "the classical nhej and other", "classical nhej and other hdr", "nhej and other hdr pathways", "other hdr pathways homologous", "hdr pathways homologous recombination", "pathways homologous recombination repair", "homologous recombination repair hrr", "repair hrr and", "hrr and single strand", "single strand annealing ssa", "ssa mmej does", "mmej does not require atm", "does not require atm activation.", "not require atm activation. in", "require atm activation. in fact", "activation. in fact atm", "in fact atm activation", "fact atm activation inhibits", "atm activation inhibits mmej. therefore", "inhibits mmej. therefore mmej", "mmej. therefore mmej may", "therefore mmej may be", "mmej may be triggered when", "may be triggered when the", "be triggered when the amount", "triggered when the amount of", "when the amount of dna", "the amount of dna double", "amount of dna double strand", "of dna double strand breaks", "double strand breaks dsbs", "breaks dsbs overwhelms", "dsbs overwhelms dna repair", "overwhelms dna repair machinery of", "dna repair machinery of higher", "repair machinery of higher fidelity", "machinery of higher fidelity or", "of higher fidelity or when", "higher fidelity or when cells", "fidelity or when cells are", "or when cells are deficient", "when cells are deficient in", "cells are deficient in components", "are deficient in components of", "deficient in components of high", "in components of high fidelity", "components of high fidelity dna", "of high fidelity dna repair.

              mmej", "high fidelity dna repair.

              mmej is", "fidelity dna repair.

              mmej is initiated", "dna repair.

              mmej is initiated by", "repair.

              mmej is initiated by a", "is initiated by a limited", "initiated by a limited resection", "by a limited resection of", "a limited resection of dna", "limited resection of dna dsb", "resection of dna dsb ends", "of dna dsb ends by", "dna dsb ends by the", "dsb ends by the mrn", "ends by the mrn complex", "the mrn complex mre11a:rad50:nbn", "complex mre11a:rad50:nbn and", "ctip in the", "in the absence of cdk2", "the absence of cdk2 mediated", "absence of cdk2 mediated rbbp8", "of cdk2 mediated rbbp8 phosphorylation", "cdk2 mediated rbbp8 phosphorylation and", "mediated rbbp8 phosphorylation and related", "rbbp8 phosphorylation and related brca1:bard1", "phosphorylation and related brca1:bard1 recruitment", "related brca1:bard1 recruitment yun", "brca1:bard1 recruitment yun and", "recruitment yun and hiom", "yun and hiom 2009 .", "and hiom 2009 . single", "hiom 2009 . single strand", "2009 . single strand dna", "single strand dna ssdna", "dna ssdna at", "ssdna at resected dna", "at resected dna dsb ends", "resected dna dsb ends recruits", "dna dsb ends recruits parp1", "dsb ends recruits parp1 or", "ends recruits parp1 or parp2", "recruits parp1 or parp2 homo", "or parp2 homo or", "parp2 homo or heterodimers", "or heterodimers together with", "heterodimers together with dna", "together with dna polymerase theta", "dna polymerase theta polq", "theta polq and", "polq and fen1 5'", "and fen1 5' flap endonuclease.", "fen1 5' flap endonuclease. in", "5' flap endonuclease. in a", "flap endonuclease. in a poorly", "endonuclease. in a poorly studied", "in a poorly studied sequence", "a poorly studied sequence of", "poorly studied sequence of events", "sequence of events polq", "of events polq promotes", "events polq promotes the", "polq promotes the annealing of", "promotes the annealing of two", "the annealing of two 3'", "annealing of two 3' ssdna", "of two 3' ssdna overhangs", "two 3' ssdna overhangs through", "3' ssdna overhangs through microhomologous", "ssdna overhangs through microhomologous regions", "overhangs through microhomologous regions that", "through microhomologous regions that are", "microhomologous regions that are optimally", "regions that are optimally 10", "that are optimally 10 19", "are optimally 10 19 nucleotides", "optimally 10 19 nucleotides long.", "10 19 nucleotides long. using", "19 nucleotides long. using analogy", "nucleotides long. using analogy with", "long. using analogy with polb", "using analogy with polb mediated", "analogy with polb mediated long", "with polb mediated long patch", "polb mediated long patch base", "mediated long patch base excision", "long patch base excision repair", "base excision repair ber", "ber it is", "it is plausible that parp1", "plausible that parp1 or", "that parp1 or parp2", "or parp2 dimers coordinate", "parp2 dimers coordinate the", "dimers coordinate the extension of", "coordinate the extension of annealed", "the extension of annealed 3'", "extension of annealed 3' ssdna", "of annealed 3' ssdna overhangs", "annealed 3' ssdna overhangs via", "3' ssdna overhangs via polq", "ssdna overhangs via polq mediated", "overhangs via polq mediated strand", "via polq mediated strand displacement", "polq mediated strand displacement synthesis", "mediated strand displacement synthesis with", "strand displacement synthesis with fen1", "displacement synthesis with fen1 mediated", "synthesis with fen1 mediated cleavage", "with fen1 mediated cleavage of", "fen1 mediated cleavage of the", "mediated cleavage of the resulting", "cleavage of the resulting 5'", "of the resulting 5' flaps", "resulting 5' flaps liang", "5' flaps liang et", "flaps liang et al.", "et al. 2005 mansour", "al. 2005 mansour et", "2005 mansour et al.", "et al. 2011 sharma", "al. 2011 sharma et", "2011 sharma et al.", "et al. 2015 kent", "al. 2015 kent et", "2015 kent et al.", "et al. 2015 ciccaldi", "al. 2015 ciccaldi et", "2015 ciccaldi et al.", "et al. 2015 mateos", "al. 2015 mateos gomez", "2015 mateos gomez et", "mateos gomez et al. 2015", "gomez et al. 2015 .", "et al. 2015 . the", "al. 2015 . the mrn", "2015 . the mrn complex", ". the mrn complex subsequently", "the mrn complex subsequently recruits", "mrn complex subsequently recruits dna", "complex subsequently recruits dna ligase", "subsequently recruits dna ligase 3", "dna ligase 3 lig3", "3 lig3 bound", "lig3 bound to xrcc1", "bound to xrcc1 lig3:xrcc1", "xrcc1 lig3:xrcc1 to", "lig3:xrcc1 to ligate the", "to ligate the remaining single", "ligate the remaining single strand", "the remaining single strand nicks", "single strand nicks ssbs", "nicks ssbs at", "ssbs at mmej sites", "at mmej sites della", "mmej sites della maria", "sites della maria et", "della maria et al. 2011", "maria et al. 2011 .

              similar", "et al. 2011 .

              similar to", "al. 2011 .

              similar to single", "2011 .

              similar to single strand", ".

              similar to single strand annealing", "ssa mmej leads", "mmej leads to deletion of", "leads to deletion of one", "to deletion of one of", "deletion of one of the", "of one of the microhomology", "one of the microhomology regions", "of the microhomology regions used", "the microhomology regions used for", "microhomology regions used for annealing", "regions used for annealing and", "used for annealing and the", "for annealing and the dna", "annealing and the dna sequence", "and the dna sequence in", "the dna sequence in between", "dna sequence in between two", "sequence in between two annealed", "in between two annealed microhomology", "between two annealed microhomology regions.", "two annealed microhomology regions. mmej", "microhomology regions. mmej just", "regions. mmej just like", "mmej just like classical", "like classical nhej can", "classical nhej can result", "nhej can result in", "can result in genomic translocations", "in genomic translocations ghezraoui", "genomic translocations ghezraoui et", "translocations ghezraoui et al.", "ghezraoui et al. 2014 .", "et al. 2014 . in", "al. 2014 . in addition", ". in addition since", "in addition since polq", "addition since polq is", "since polq is an error", "polq is an error prone", "is an error prone dna", "an error prone dna polymerase", "prone dna polymerase mmej", "dna polymerase mmej introduces", "polymerase mmej introduces frequent", "mmej introduces frequent base substitutions", "frequent base substitutions ceccaldi", "base substitutions ceccaldi et", "substitutions ceccaldi et al.", "ceccaldi et al. 2015 ." ] }, { "record_id": "GLY_000594_1_1075", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5687583", "r hsa", "hsa 5687583", "r hsa 5687583" ] }, { "record_id": "GLY_000594_1_1075", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc34a2", "slc34a2 causes", "causes palm", "defective 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francisco et", "francisco et al.", "2013 whitsett", "whitsett et al.", "et al. 2015", "al. 2015 .", "the human gene slc34a2", "human gene slc34a2 encodes", "gene slc34a2 encodes napi", "slc34a2 encodes napi 2b", "encodes napi 2b which", "napi 2b which is", "2b which is abundantly", "which is abundantly expressed", "is abundantly expressed in", "abundantly expressed in lung", "expressed in lung and", "in lung and to", "lung and to a", "and to a lesser", "to a lesser degree", "a lesser degree in", "lesser degree in epithelia", "degree in epithelia of", "in epithelia of other", "epithelia of other tissues", "of other tissues including", "other tissues including small", "tissues including small intestine", "small intestine pancreas", "prostate and kidney.", "and kidney. in the", "kidney. in the lung", "the lung slc34a2", "lung slc34a2 is", "slc34a2 is expressed only", "is expressed only in", "expressed only in alveolar", "only in alveolar type", "in alveolar type ii", "alveolar type ii 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              ", "

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              ", ".

              otu", "

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              ", "2009 .

              otu", ".

              otu family", "

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              ", "al. 2009 .

              otu", "2009 .

              otu family", ".

              otu family dubs", "

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2009 mevissen et", "2009 mevissen et al.", "mevissen et al. 2013 .", "et al. 2013 . a20", "al. 2013 . a20 prefers", "2013 . a20 prefers k48", ". a20 prefers k48 linked", "a20 prefers k48 linked chains", "k48 linked chains cezanne", "linked chains cezanne is", "chains cezanne is specific", "cezanne is specific for k11", "is specific for k11 linked", "specific for k11 linked chains", "k11 linked chains and", "linked chains and trabid", "chains and trabid acts", "and trabid acts on both", "trabid acts on both k29", "on both k29 k33", "both k29 k33 and", "k29 k33 and k63", "k33 and k63 linked poly", "and k63 linked poly ub", "linked poly ub licchesi", "poly ub licchesi et", "ub licchesi et al.", "et al. 2011 komander", "al. 2011 komander &", "2011 komander & barford", "& barford 2008 bremm", "barford 2008 bremm et", "2008 bremm et al.", "et al. 2010 mevissen", "al. 2010 mevissen et", "2010 mevissen et al.", "et al. 2013 . the", "al. 2013 . the active", "2013 . the active site", ". the 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"record_id": "GLY_000594_1_1080", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5693571", "r hsa", "hsa 5693571", "r hsa 5693571" ] }, { "record_id": "GLY_000594_1_1080", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nonhomologous end", "end joining", "nonhomologous end joining", "joining nhej", "end joining nhej", "nonhomologous end joining nhej", "the nonhomologous", "pathway is", "is initiated", "initiated in", "in response", "response to", "to the", "the formation", "formation of", "of dna", "dna double", "double strand", "strand breaks", "induced by", "by dna", "dna damaging", "damaging agents", "such as", "as ionizing", "ionizing radiation.", "radiation. dna", "dna dsbs", "dsbs are", "are recognized", "recognized by", "by the", "the mrn", "mrn complex", "leading to", "to atm", "atm activation", "activation and", "and atm", "atm dependent", "dependent recruitment", "recruitment of", "of a", "a number", "number of", "dna damage", "damage checkpoint", "checkpoint and", "and repair", "repair proteins", "proteins to", "to dna", "dna dsb", "dsb sites", "lee and", "and paull", "paull 2005", "2005 .", ". the", "the atm", "atm phosphorylated", "phosphorylated mrn", "mdc1 and", "and h2afx", "h2afx containing", "containing nucleosomes", "gamma h2ax", "serve as", "as scaffolds", "scaffolds for", "for the", "of nuclear", "nuclear foci", "foci known", "known as", "ionizing radiation", "radiation induced", "induced foci", "gatei et", "et al.", "al. 2000", "paull et", "stewart et", "al. 2003", "stucki et", "al. 2005", ". ultimately", "both brca1:bard1", "brca1:bard1 heterodimers", "heterodimers and", "and tp53bp1", "are recruited", "recruited to", "to irif", "wang et", "al. 2007", "pei et", "al. 2011", "mallette et", "al. 2012", "which is", "is necessary", "necessary for", "for atm", "atm mediated", "mediated chek2", "chek2 activation", "al. 2002", "wilson et", "al. 2008", "2008 .", ". in", "in g1", "g1 cells", "tp53bp1 promotes", "promotes nhej", "nhej by", "by recruiting", "recruiting rif1", "rif1 and", "and pax1ip", "which displaces", "displaces brca1:bard1", "brca1:bard1 and", "and associated", "associated proteins", "proteins from", "from the", "the dna", "dsb site", "site and", "and prevents", "prevents resection", "resection of", "dsbs needed", "needed for", "for homologous", "homologous recombination", "recombination repair", "escribano diaz", "diaz et", "al. 2013", "zimmermann et", "callen et", "2013 .", ". tp53bp1", "tp53bp1 also", "also plays", "plays an", "an important", "important role", "role in", "in atm", "mediated phosphorylation", "phosphorylation of", "of dclre1c", "riballo et", "al. 2004", "al. 2014", "2014 .", ". ku70:ku80", "ku70:ku80 heterodimer", "also known", "as the", "the ku", "ku complex", "complex or", "or xrcc5:xrcc6", "binds dna", "dsb ends", "competing away", "away the", "complex and", "and preventing", "preventing mrn", "mrn mediated", "mediated resection", "walker et", "al. 2001", "sun et", "2012 .", "the catalytic", "catalytic subunit", "subunit of", "of the", "dna dependent", "dependent protein", "protein kinase", "dna pkcs", "is then", "then recruited", "dna bound", "bound ku", "ku to", "to form", "form the", "dna pk", "pk holoenzyme.", "holoenzyme. two", "two dna", "pk complexes", "one at", "at each", "each side", "side of", "the break", "bring dna", "ends together", "joining them", "them in", "in a", "a synaptic", "synaptic complex", "gottlieb 1993", "yoo and", "and dynan", "dynan 2000", "2000 .", ". dna", "pk complex", "complex recruits", "recruits dclre1c", "ma et", "2002 .", ". prkdc", "prkdc mediated", "as well", "well as", "as prkdc", "prkdc autophosphorylation", "enables dclre1c", "dclre1c to", "to trim", "trim 3'", "and 5'", "5' overhangs", "overhangs at", "at dna", "preparing them", "them for", "for ligation", "niewolik et", "al. 2006", "2006 .", "the binding", "binding of", "of inositol", "inositol phosphate", "phosphate may", "may additionally", "additionally stimulate", "stimulate the", "catalytic activity", "activity of", "of prkdc", "hanakahi et", ". other", "other factors", "as polynucleotide", "polynucleotide kinase", "tdp1 or", "or tdp2", "tdp2 may", "may remove", "remove unligatable", "unligatable damaged", "damaged nucleotides", "nucleotides from", "from 5'", "and 3'", "3' ends", "ends of", "the dsb", "converting them", "them to", "to ligatable", "ligatable substrates", "inamdar et", "gomez herreros", "herreros et", "dna ligase", "ligase 4", "in complex", "complex with", "with xrcc4", "is recruited", "ligatable dna", "together with", "with the", "the xlf", "homodimer and", "and dna", "dna polymerases", "polymerases mu", "and/or lambda", "mcelhinny et", "hsu et", "malu et", "ahnesorg et", "mahajan et", "lee et", "fan and", "and wu", "wu 2004", "2004 .", ". after", "after poll", "poll and/or", "and/or polm", "polm fill", "fill 1", "or 2", "2 nucleotide", "nucleotide long", "long single", "single strand", "strand gaps", "gaps at", "at aligned", "aligned dna", "xrcc4:lig4 performs", "performs the", "the ligation", "ligation of", "of broken", "broken dna", "dna strands", "thus completing", "completing nhej.", "nhej. the", "the presence", "presence of", "of nhej1", "nhej1 homodimer", "homodimer facilitates", "facilitates the", "ligation step", "especially at", "at mismatched", "mismatched dsb", "tsai et", "2007 .", ". depending", "depending on", "on other", "other types", "types of", "damage present", "present at", "nhej can", "can result", "result in", "in error", "error free", "free products", "produce dsdna", "dsdna with", "with microdeletions", "microdeletions and/or", "and/or mismatched", "mismatched bases", "or result", "in translocations", "reviewed by", "by povrik", "povrik et", "the nonhomologous end", "nhej pathway", "pathway is initiated", "is initiated in", "initiated in response", "in response to", "response to the", "to the formation", "the formation of", "formation of dna", "of dna double", "dna double strand", "double strand breaks", "breaks dsbs", "dsbs induced", "induced by dna", "by dna damaging", "dna damaging agents", "agents such", "such as ionizing", "as ionizing radiation.", "ionizing radiation. dna", "radiation. dna dsbs", "dna dsbs are", "dsbs are recognized", "are recognized by", "recognized by the", "by the mrn", "the mrn complex", "complex mre11a:rad50:nbn", "leading to atm", "to atm activation", "atm activation and", "activation and atm", "and atm dependent", "atm dependent recruitment", "dependent recruitment of", "recruitment of a", "of a number", "a number of", "number of dna", "of dna damage", "dna damage checkpoint", "damage checkpoint and", "checkpoint and repair", "and repair proteins", "repair proteins to", "proteins to dna", "to dna dsb", "dna dsb sites", "sites lee", "lee and paull", "and paull 2005", "paull 2005 .", "2005 . the", ". the atm", "the atm phosphorylated", "atm phosphorylated mrn", "phosphorylated mrn complex", "complex mdc1", "mdc1 and h2afx", "and h2afx containing", "h2afx containing nucleosomes", "nucleosomes gamma", "h2ax serve", "serve as scaffolds", "as scaffolds for", "scaffolds for the", "for the formation", "formation of nuclear", "of nuclear foci", "nuclear foci known", "foci known as", "known as ionizing", "as ionizing radiation", "ionizing radiation induced", "radiation induced foci", "foci irif", "gatei et al.", "et al. 2000", "2000 paull", "paull et al.", "2000 stewart", "stewart et al.", "et al. 2003", "2003 stucki", "stucki et al.", "et al. 2005", "al. 2005 .", "2005 . ultimately", "ultimately both", "both brca1:bard1 heterodimers", "brca1:bard1 heterodimers and", "heterodimers and tp53bp1", "tp53bp1 53bp1", "53bp1 are", "are recruited to", "recruited to irif", "irif wang", "wang et al.", "et al. 2007", "2007 pei", "pei et al.", "et al. 2011", "2011 mallette", "mallette et al.", "et al. 2012", "which is necessary", "is necessary for", "necessary for atm", "for atm mediated", "atm mediated chek2", "mediated chek2 activation", "activation wang", "et al. 2002", "2002 wilson", "wilson et al.", "et al. 2008", "al. 2008 .", "2008 . in", ". in g1", "in g1 cells", "cells tp53bp1", "tp53bp1 promotes nhej", "promotes nhej by", "nhej by recruiting", "by recruiting rif1", "recruiting rif1 and", "rif1 and pax1ip", "pax1ip which", "which displaces brca1:bard1", "displaces brca1:bard1 and", "brca1:bard1 and associated", "and associated proteins", "associated proteins from", "proteins from the", "from the dna", "the dna dsb", "dna dsb site", "dsb site and", "site and prevents", "and prevents resection", "prevents resection of", "resection of dna", "of dna dsbs", "dna dsbs needed", "dsbs needed for", "needed for homologous", "for homologous recombination", "homologous recombination repair", "repair hrr", "escribano diaz et", "diaz et al.", "et al. 2013", "2013 zimmermann", "zimmermann et al.", "2013 callen", "callen et al.", "al. 2013 .", "2013 . tp53bp1", ". tp53bp1 also", "tp53bp1 also plays", "also plays an", "plays an important", "an important role", "important role in", "role in atm", "in atm mediated", "atm mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of dclre1c", "dclre1c artemis", "riballo et al.", "et al. 2004", "2004 wang", "et al. 2014", "al. 2014 .", "2014 . ku70:ku80", ". ku70:ku80 heterodimer", "heterodimer also", "also known as", "known as the", "as the ku", "the ku complex", "ku complex or", "complex or xrcc5:xrcc6", "xrcc5:xrcc6 binds", "binds dna dsb", "dna dsb ends", "ends competing", "competing away the", "away the mrn", "mrn complex and", "complex and preventing", "and preventing mrn", "preventing mrn mediated", "mrn mediated resection", "mediated resection of", "of dna dsb", "ends walker", "walker et al.", "et al. 2001", "2001 sun", "sun et al.", "al. 2012 .", "2012 . the", ". the catalytic", "the catalytic subunit", "catalytic subunit of", "subunit of the", "of the dna", "the dna dependent", "dna dependent protein", "dependent protein kinase", "kinase dna", "pkcs prkdc", "prkdc is", "is then recruited", "then recruited to", "recruited to dna", "to dna bound", "dna bound ku", "bound ku to", "ku to form", "to form the", "form the dna", "the dna pk", "dna pk holoenzyme.", "pk holoenzyme. two", "holoenzyme. two dna", "two dna pk", "dna pk complexes", "complexes one", "one at each", "at each side", "each side of", "side of the", "of the break", "break bring", "bring dna dsb", "dsb ends together", "together joining", "joining them in", "them in a", "in a synaptic", "a synaptic complex", "complex gottlieb", "1993 yoo", "yoo and dynan", "and dynan 2000", "dynan 2000 .", "2000 . dna", ". dna pk", "dna pk complex", "pk complex recruits", "complex recruits dclre1c", "artemis to", "ends ma", "ma et al.", "al. 2002 .", "2002 . prkdc", ". prkdc mediated", "prkdc mediated phosphorylation", "dclre1c as", "as well as", "well as prkdc", "as prkdc autophosphorylation", "autophosphorylation enables", "enables dclre1c to", "dclre1c to trim", "to trim 3'", "3' and", "and 5' overhangs", "5' overhangs at", "overhangs at dna", "at dna dsbs", "dsbs preparing", "preparing them for", "them for ligation", "ligation ma", "2002 ma", "2005 niewolik", "niewolik et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the binding", "the binding of", "binding of inositol", "of inositol phosphate", "inositol phosphate may", "phosphate may additionally", "may additionally stimulate", "additionally stimulate the", "stimulate the catalytic", "the catalytic activity", "catalytic activity of", "activity of prkdc", "prkdc hanakahi", "hanakahi et al.", "al. 2000 .", "2000 . other", ". other factors", "factors such", "such as polynucleotide", "as polynucleotide kinase", "kinase pnk", "tdp1 or tdp2", "or tdp2 may", "tdp2 may remove", "may remove unligatable", "remove unligatable damaged", "unligatable damaged nucleotides", "damaged nucleotides from", "nucleotides from 5'", "5' and", "and 3' ends", "3' ends of", "ends of the", "of the dsb", "dsb converting", "converting them to", "them to ligatable", "to ligatable substrates", "substrates inamdar", "inamdar et al.", "2002 gomez", "gomez herreros et", "herreros et al.", "2013 . dna", ". dna ligase", "dna ligase 4", "4 lig4", "lig4 in", "in complex with", "complex with xrcc4", "xrcc4 xrcc4:lig4", "xrcc4:lig4 is", "is recruited to", "recruited to ligatable", "to ligatable dna", "ligatable dna dsb", "ends together with", "together with the", "with the xlf", "xlf nhej1", "homodimer and dna", "and dna polymerases", "dna polymerases mu", "mu polm", "polm and/or", "lambda poll", "mcelhinny et al.", "2000 hsu", "hsu et al.", "2002 malu", "malu et al.", "2002 ahnesorg", "ahnesorg et al.", "2006 mahajan", "mahajan et al.", "2002 lee", "lee et al.", "2004 fan", "fan and wu", "and wu 2004", "wu 2004 .", "2004 . after", ". after poll", "after poll and/or", "poll and/or polm", "and/or polm fill", "polm fill 1", "1 or", "or 2 nucleotide", "2 nucleotide long", "nucleotide long single", "long single strand", "single strand gaps", "strand gaps at", "gaps at aligned", "at aligned dna", "aligned dna dsb", "ends xrcc4:lig4", "xrcc4:lig4 performs the", "performs the ligation", "the ligation of", "ligation of broken", "of broken dna", "broken dna strands", "strands thus", "thus completing nhej.", "completing nhej. the", "nhej. the presence", "the presence of", "presence of nhej1", "of nhej1 homodimer", "nhej1 homodimer facilitates", "homodimer facilitates the", "facilitates the ligation", "the ligation step", "step especially", "especially at mismatched", "at mismatched dsb", "mismatched dsb ends", "ends tsai", "tsai et al.", "al. 2007 .", "2007 . depending", ". depending on", "depending on other", "on other types", "other types of", "types of dna", "dna damage present", "damage present at", "present at dna", "dsbs nhej", "nhej can result", "can result in", "result in error", "in error free", "error free products", "products produce", "produce dsdna with", "dsdna with microdeletions", "with microdeletions and/or", "microdeletions and/or mismatched", "and/or mismatched bases", "bases or", "or result in", "result in translocations", "translocations reviewed", "reviewed by povrik", "by povrik et", "povrik et al.", "the nonhomologous end joining", "nhej pathway is", "pathway is initiated in", "is initiated in response", "initiated in response to", "in response to the", "response to the formation", "to the formation of", "the formation of dna", "formation of dna double", "of dna double strand", "dna double strand breaks", "strand breaks dsbs", "dsbs induced by", "induced by dna damaging", "by dna damaging agents", "damaging agents such", "agents such as", "such as ionizing radiation.", "as ionizing radiation. dna", "ionizing radiation. dna dsbs", "radiation. dna dsbs are", "dna dsbs are recognized", "dsbs are recognized by", "are recognized by the", "recognized by the mrn", "by the mrn complex", "mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn leading", "leading to atm activation", "to atm activation and", "atm activation and atm", "activation and atm dependent", "and atm dependent recruitment", "atm dependent recruitment of", "dependent recruitment of a", "recruitment of a number", "of a number of", "a number of dna", "number of dna damage", "of dna damage checkpoint", "dna damage checkpoint and", "damage checkpoint and repair", "checkpoint and repair proteins", "and repair proteins to", "repair proteins to dna", "proteins to dna dsb", "to dna dsb sites", "dsb sites lee", "sites lee and", "lee and paull 2005", "and paull 2005 .", "paull 2005 . the", "2005 . the atm", ". the atm phosphorylated", "the atm phosphorylated mrn", "atm phosphorylated mrn complex", "mrn complex mdc1", "complex mdc1 and", "mdc1 and h2afx containing", "and h2afx containing nucleosomes", "containing nucleosomes gamma", "nucleosomes gamma h2ax", "gamma h2ax serve", "h2ax serve as", "serve as scaffolds for", "as scaffolds for the", "scaffolds for the formation", "for the formation of", "the formation of nuclear", "formation of nuclear foci", "of nuclear foci known", "nuclear foci known as", "foci known as ionizing", "known as ionizing radiation", "as ionizing radiation induced", "ionizing radiation induced foci", "induced foci irif", "irif gatei", "gatei et al. 2000", "al. 2000 paull", "2000 paull et", "paull et al. 2000", "al. 2000 stewart", "2000 stewart et", "stewart et al. 2003", "al. 2003 stucki", "2003 stucki et", "stucki et al. 2005", "et al. 2005 .", "al. 2005 . ultimately", ". ultimately both", "ultimately both brca1:bard1", "both brca1:bard1 heterodimers and", "brca1:bard1 heterodimers and tp53bp1", "and tp53bp1 53bp1", "53bp1 are recruited", "are recruited to irif", "to irif wang", "irif wang et", "wang et al. 2007", "al. 2007 pei", "2007 pei et", "pei et al. 2011", "al. 2011 mallette", "2011 mallette et", "mallette et al. 2012", "2012 which", "which is necessary for", "is necessary for atm", "necessary for atm mediated", "for atm mediated chek2", "atm mediated chek2 activation", "chek2 activation wang", "activation wang et", "wang et al. 2002", "al. 2002 wilson", "2002 wilson et", "wilson et al. 2008", "et al. 2008 .", "al. 2008 . in", "2008 . in g1", ". in g1 cells", "g1 cells tp53bp1", "cells tp53bp1 promotes", "tp53bp1 promotes nhej by", "promotes nhej by recruiting", "nhej by recruiting rif1", "by recruiting rif1 and", "recruiting rif1 and pax1ip", "and pax1ip which", "pax1ip which displaces", "which displaces brca1:bard1 and", "displaces brca1:bard1 and associated", "brca1:bard1 and associated proteins", "and associated proteins from", "associated proteins from the", "proteins from the dna", "from the dna dsb", "the dna dsb site", "dna dsb site and", "dsb site and prevents", "site and prevents resection", "and prevents resection of", "prevents resection of dna", "resection of dna dsbs", "of dna dsbs needed", "dna dsbs needed for", "dsbs needed for homologous", "needed for homologous recombination", "for homologous recombination repair", "recombination repair hrr", "hrr escribano", "escribano diaz et al.", "diaz et al. 2013", "al. 2013 zimmermann", "2013 zimmermann et", "zimmermann et al. 2013", "al. 2013 callen", "2013 callen et", "callen et al. 2013", "et al. 2013 .", "al. 2013 . tp53bp1", "2013 . tp53bp1 also", ". tp53bp1 also plays", "tp53bp1 also plays an", "also plays an important", "plays an important role", "an important role in", "important role in atm", "role in atm mediated", "in atm mediated phosphorylation", "atm mediated phosphorylation of", "mediated phosphorylation of dclre1c", "of dclre1c artemis", "artemis riballo", "riballo et al. 2004", "al. 2004 wang", "2004 wang et", "wang et al. 2014", "et al. 2014 .", "al. 2014 . ku70:ku80", "2014 . ku70:ku80 heterodimer", "ku70:ku80 heterodimer also", "heterodimer also known", "also known as the", "known as the ku", "as the ku complex", "the ku complex or", "ku complex or xrcc5:xrcc6", "or xrcc5:xrcc6 binds", "xrcc5:xrcc6 binds dna", "binds dna dsb ends", "dsb ends competing", "ends competing away", "competing away the mrn", "away the mrn complex", "the mrn complex and", "mrn complex and preventing", "complex and preventing mrn", "and preventing mrn mediated", "preventing mrn mediated resection", "mrn mediated resection of", "mediated resection of dna", "resection of dna dsb", "of dna dsb ends", "dsb ends walker", "ends walker et", "walker et al. 2001", "al. 2001 sun", "2001 sun et", "sun et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the catalytic", ". the catalytic subunit", "the catalytic subunit of", "catalytic subunit of the", "subunit of the dna", "of the dna dependent", "the dna dependent protein", "dna dependent protein kinase", "protein kinase dna", "kinase dna pkcs", "dna pkcs prkdc", "prkdc is then", "is then recruited to", "then recruited to dna", "recruited to dna bound", "to dna bound ku", "dna bound ku to", "bound ku to form", "ku to form the", "to form the dna", "form the dna pk", "the dna pk holoenzyme.", "dna pk holoenzyme. two", "pk holoenzyme. two dna", "holoenzyme. two dna pk", "two dna pk complexes", "pk complexes one", "complexes one at", "one at each side", "at each side of", "each side of the", "side of the break", "the break bring", "break bring dna", "bring dna dsb ends", "dna dsb ends together", "ends together joining", "together joining them", "joining them in a", "them in a synaptic", "in a synaptic complex", "synaptic complex gottlieb", "complex gottlieb 1993", "gottlieb 1993 yoo", "1993 yoo and", "yoo and dynan 2000", "and dynan 2000 .", "dynan 2000 . dna", "2000 . dna pk", ". dna pk complex", "dna pk complex recruits", "pk complex recruits dclre1c", "recruits dclre1c artemis", "artemis to dna", "to dna dsb ends", "dsb ends ma", "ends ma et", "ma et al. 2002", "et al. 2002 .", "al. 2002 . prkdc", "2002 . prkdc mediated", ". prkdc mediated phosphorylation", "prkdc mediated phosphorylation of", "of dclre1c as", "dclre1c as well", "as well as prkdc", "well as prkdc autophosphorylation", "prkdc autophosphorylation enables", "autophosphorylation enables dclre1c", "enables dclre1c to trim", "dclre1c to trim 3'", "trim 3' and", "3' and 5'", "and 5' overhangs at", "5' overhangs at dna", "overhangs at dna dsbs", "dna dsbs preparing", "dsbs preparing them", "preparing them for ligation", "for ligation ma", "ligation ma et", "al. 2002 ma", "2002 ma et", "ma et al. 2005", "al. 2005 niewolik", "2005 niewolik et", "niewolik et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the binding", ". the binding of", "the binding of inositol", "binding of inositol phosphate", "of inositol phosphate may", "inositol phosphate may additionally", "phosphate may additionally stimulate", "may additionally stimulate the", "additionally stimulate the catalytic", "stimulate the catalytic activity", "the catalytic activity of", "catalytic activity of prkdc", "of prkdc hanakahi", "prkdc hanakahi et", "hanakahi et al. 2000", "et al. 2000 .", "al. 2000 . other", "2000 . other factors", "other factors such", "factors such as", "such as polynucleotide kinase", "polynucleotide kinase pnk", "pnk tdp1", "tdp1 or tdp2 may", "or tdp2 may remove", "tdp2 may remove unligatable", "may remove unligatable damaged", "remove unligatable damaged nucleotides", "unligatable damaged nucleotides from", "damaged nucleotides from 5'", "from 5' and", "5' and 3'", "and 3' ends of", "3' ends of the", "ends of the dsb", "the dsb converting", "dsb converting them", "converting them to ligatable", "them to ligatable substrates", "ligatable substrates inamdar", "substrates inamdar et", "inamdar et al. 2002", "al. 2002 gomez", "2002 gomez herreros", "gomez herreros et al.", "herreros et al. 2013", "al. 2013 . dna", "2013 . dna ligase", ". dna ligase 4", "ligase 4 lig4", "lig4 in complex", "in complex with xrcc4", "with xrcc4 xrcc4:lig4", "xrcc4:lig4 is recruited", "is recruited to ligatable", "recruited to ligatable dna", "to ligatable dna dsb", "ligatable dna dsb ends", "dsb ends together with", "ends together with the", "together with the xlf", "the xlf nhej1", "nhej1 homodimer and", "homodimer and dna polymerases", "and dna polymerases mu", "polymerases mu polm", "polm and/or lambda", "and/or lambda poll", "poll mcelhinny", "mcelhinny et al. 2000", "al. 2000 hsu", "2000 hsu et", "hsu et al. 2002", "al. 2002 malu", "2002 malu et", "malu et al. 2002", "al. 2002 ahnesorg", "2002 ahnesorg et", "ahnesorg et al. 2006", "al. 2006 mahajan", "2006 mahajan et", "mahajan et al. 2002", "al. 2002 lee", "2002 lee et", "lee et al. 2004", "al. 2004 fan", "2004 fan and", "fan and wu 2004", "and wu 2004 .", "wu 2004 . after", "2004 . after poll", ". after poll and/or", "after poll and/or polm", "poll and/or polm fill", "and/or polm fill 1", "fill 1 or", "1 or 2", "or 2 nucleotide long", "2 nucleotide long single", "nucleotide long single strand", "long single strand gaps", "single strand gaps at", "strand gaps at aligned", "gaps at aligned dna", "at aligned dna dsb", "aligned dna dsb ends", "dsb ends xrcc4:lig4", "ends xrcc4:lig4 performs", "xrcc4:lig4 performs the ligation", "performs the ligation of", "the ligation of broken", "ligation of broken dna", "of broken dna strands", "dna strands thus", "strands thus completing", "thus completing nhej. the", "completing nhej. the presence", "nhej. the presence of", "the presence of nhej1", "presence of nhej1 homodimer", "of nhej1 homodimer facilitates", "nhej1 homodimer facilitates the", "homodimer facilitates the ligation", "facilitates the ligation step", "ligation step especially", "step especially at", "especially at mismatched dsb", "at mismatched dsb ends", "dsb ends tsai", "ends tsai et", "tsai et al. 2007", "et al. 2007 .", "al. 2007 . depending", "2007 . depending on", ". depending on other", "depending on other types", "on other types of", "other types of dna", "types of dna damage", "of dna damage present", "dna damage present at", "damage present at dna", "present at dna dsbs", "dna dsbs nhej", "dsbs nhej can", "nhej can result in", "can result in error", "result in error free", "in error free products", "free products produce", "products produce dsdna", "produce dsdna with microdeletions", "dsdna with microdeletions and/or", "with microdeletions and/or mismatched", "microdeletions and/or mismatched bases", "mismatched bases or", "bases or result", "or result in translocations", "in translocations reviewed", "translocations reviewed by", "reviewed by povrik et", "by povrik et al.", "povrik et al. 2012", "joining nhej pathway", "nhej pathway is initiated", "pathway is initiated in response", "is initiated in response to", "initiated in response to the", "in response to the formation", "response to the formation of", "to the formation of dna", "the formation of dna double", "formation of dna double strand", "of dna double strand breaks", "double strand breaks dsbs", "breaks dsbs induced", "dsbs induced by dna", "induced by dna damaging agents", "dna damaging agents such", "damaging agents such as", "agents such as ionizing", "such as ionizing radiation. dna", "as ionizing radiation. dna dsbs", "ionizing radiation. dna dsbs are", "radiation. dna dsbs are recognized", "dna dsbs are recognized by", "dsbs are recognized by the", "are recognized by the mrn", "recognized by the mrn complex", "the mrn complex mre11a:rad50:nbn", "mre11a:rad50:nbn leading to", "leading to atm activation and", "to atm activation and atm", "atm activation and atm dependent", "activation and atm dependent recruitment", "and atm dependent recruitment of", "atm dependent recruitment of a", "dependent recruitment of a number", "recruitment of a number of", "of a number of dna", "a number of dna damage", "number of dna damage checkpoint", "of dna damage checkpoint and", "dna damage checkpoint and repair", "damage checkpoint and repair proteins", "checkpoint and repair proteins to", "and repair proteins to dna", "repair proteins to dna dsb", "proteins to dna dsb sites", "dna dsb sites lee", "dsb sites lee and", "sites lee and paull", "lee and paull 2005 .", "and paull 2005 . the", "paull 2005 . the atm", "2005 . the atm phosphorylated", ". the atm phosphorylated mrn", "the atm phosphorylated mrn complex", "phosphorylated mrn complex mdc1", "mrn complex mdc1 and", "complex mdc1 and h2afx", "mdc1 and h2afx containing nucleosomes", "h2afx containing nucleosomes gamma", "containing nucleosomes gamma h2ax", "gamma h2ax serve as", "h2ax serve as scaffolds", "serve as scaffolds for the", "as scaffolds for the formation", "scaffolds for the formation of", "for the formation of nuclear", "the formation of nuclear foci", "formation of nuclear foci known", "of nuclear foci known as", "nuclear foci known as ionizing", "foci known as ionizing radiation", "known as ionizing radiation induced", "as ionizing radiation induced foci", "radiation induced foci irif", "irif gatei et", "et al. 2000 paull", "al. 2000 paull et", "2000 paull et al.", "et al. 2000 stewart", "al. 2000 stewart et", "2000 stewart et al.", "et al. 2003 stucki", "al. 2003 stucki et", "2003 stucki et al.", "stucki et al. 2005 .", "et al. 2005 . ultimately", "2005 . ultimately both", ". ultimately both brca1:bard1", "ultimately both brca1:bard1 heterodimers", "both brca1:bard1 heterodimers and tp53bp1", "heterodimers and tp53bp1 53bp1", "tp53bp1 53bp1 are", "53bp1 are recruited to", "recruited to irif wang", "to irif wang et", "irif wang et al.", "et al. 2007 pei", "al. 2007 pei et", "2007 pei et al.", "et al. 2011 mallette", "al. 2011 mallette et", "2011 mallette et al.", "al. 2012 which", "2012 which is", "which is necessary for atm", "is necessary for atm mediated", "necessary for atm mediated chek2", "for atm mediated chek2 activation", "mediated chek2 activation wang", "chek2 activation wang et", "activation wang et al.", "et al. 2002 wilson", "al. 2002 wilson et", "2002 wilson et al.", "wilson et al. 2008 .", "et al. 2008 . in", "al. 2008 . in g1", "2008 . in g1 cells", "in g1 cells tp53bp1", "g1 cells tp53bp1 promotes", "cells tp53bp1 promotes nhej", "tp53bp1 promotes nhej by recruiting", "promotes nhej by recruiting rif1", "nhej by recruiting rif1 and", "by recruiting rif1 and pax1ip", "rif1 and pax1ip which", "and pax1ip which displaces", "pax1ip which displaces brca1:bard1", "which displaces brca1:bard1 and associated", "displaces brca1:bard1 and associated proteins", "brca1:bard1 and associated proteins from", "and associated proteins from the", "associated proteins from the dna", "proteins from the dna dsb", "from the dna dsb site", "the dna dsb site and", "dna dsb site and prevents", "dsb site and prevents resection", "site and prevents resection of", "and prevents resection of dna", "prevents resection of dna dsbs", "resection of dna dsbs needed", "of dna dsbs needed for", "dna dsbs needed for homologous", "dsbs needed for homologous recombination", "needed for homologous recombination repair", "homologous recombination repair hrr", "hrr escribano diaz", "escribano diaz et al. 2013", "et al. 2013 zimmermann", "al. 2013 zimmermann et", "2013 zimmermann et al.", "et al. 2013 callen", "al. 2013 callen et", "2013 callen et al.", "callen et al. 2013 .", "et al. 2013 . tp53bp1", "al. 2013 . tp53bp1 also", "2013 . tp53bp1 also plays", ". tp53bp1 also plays an", "tp53bp1 also plays an important", "also plays an important role", "plays an important role in", "an important role in atm", "important role in atm mediated", "role in atm mediated phosphorylation", "in atm mediated phosphorylation of", "atm mediated phosphorylation of dclre1c", "phosphorylation of dclre1c artemis", "artemis riballo et", "et al. 2004 wang", "al. 2004 wang et", "2004 wang et al.", "wang et al. 2014 .", "et al. 2014 . ku70:ku80", "al. 2014 . ku70:ku80 heterodimer", ". ku70:ku80 heterodimer also", "ku70:ku80 heterodimer also known", "heterodimer also known as", "also known as the ku", "known as the ku complex", "as the ku complex or", "the ku complex or xrcc5:xrcc6", "complex or xrcc5:xrcc6 binds", "or xrcc5:xrcc6 binds dna", "xrcc5:xrcc6 binds dna dsb", "dna dsb ends competing", "dsb ends competing away", "ends competing away the", "competing away the mrn complex", "away the mrn complex and", "the mrn complex and preventing", "mrn complex and preventing mrn", "complex and preventing mrn mediated", "and preventing mrn mediated resection", "preventing mrn mediated resection of", "mrn mediated resection of dna", "mediated resection of dna dsb", "resection of dna dsb ends", "dna dsb ends walker", "dsb ends walker et", "ends walker et al.", "et al. 2001 sun", "al. 2001 sun et", "2001 sun et al.", "sun et al. 2012 .", "et al. 2012 . the", "al. 2012 . the catalytic", "2012 . the catalytic subunit", ". the catalytic subunit of", "the catalytic subunit of the", "catalytic subunit of the dna", "subunit of the dna dependent", "of the dna dependent protein", "the dna dependent protein kinase", "dependent protein kinase dna", "protein kinase dna pkcs", "pkcs prkdc is", "prkdc is then recruited", "is then recruited to dna", "then recruited to dna bound", "recruited to dna bound ku", "to dna bound ku to", "dna bound ku to form", "bound ku to form the", "ku to form the dna", "to form the dna pk", "form the dna pk holoenzyme.", "the dna pk holoenzyme. two", "dna pk holoenzyme. two dna", "pk holoenzyme. two dna pk", "holoenzyme. two dna pk complexes", "dna pk complexes one", "pk complexes one at", "complexes one at each", "one at each side of", "at each side of the", "each side of the break", "of the break bring", "the break bring dna", "break bring dna dsb", "bring dna dsb ends together", "dsb ends together joining", "ends together joining them", "together joining them in", "joining them in a synaptic", "them in a synaptic complex", "a synaptic complex gottlieb", "synaptic complex gottlieb 1993", "gottlieb 1993 yoo and", "1993 yoo and dynan", "yoo and dynan 2000 .", "and dynan 2000 . dna", "dynan 2000 . dna pk", "2000 . dna pk complex", ". dna pk complex recruits", "dna pk complex recruits dclre1c", "complex recruits dclre1c artemis", "dclre1c artemis to", "artemis to dna dsb", "dna dsb ends ma", "dsb ends ma et", "ends ma et al.", "ma et al. 2002 .", "et al. 2002 . prkdc", "al. 2002 . prkdc mediated", "2002 . prkdc mediated phosphorylation", ". prkdc mediated phosphorylation of", "prkdc mediated phosphorylation of dclre1c", "phosphorylation of dclre1c as", "of dclre1c as well", "dclre1c as well as", "as well as prkdc autophosphorylation", "as prkdc autophosphorylation enables", "prkdc autophosphorylation enables dclre1c", "autophosphorylation enables dclre1c to", "enables dclre1c to trim 3'", "to trim 3' and", "trim 3' and 5'", "3' and 5' overhangs", "and 5' overhangs at dna", "5' overhangs at dna dsbs", "at dna dsbs preparing", "dna dsbs preparing them", "dsbs preparing them for", "them for ligation ma", "for ligation ma et", "ligation ma et al.", "et al. 2002 ma", "al. 2002 ma et", "2002 ma et al.", "et al. 2005 niewolik", "al. 2005 niewolik et", "2005 niewolik et al.", "niewolik et al. 2006 .", "et al. 2006 . the", "al. 2006 . the binding", "2006 . the binding of", ". the binding of inositol", "the binding of inositol phosphate", "binding of inositol phosphate may", "of inositol phosphate may additionally", "inositol phosphate may additionally stimulate", "phosphate may additionally stimulate the", "may additionally stimulate the catalytic", "additionally stimulate the catalytic activity", "stimulate the catalytic activity of", "the catalytic activity of prkdc", "activity of prkdc hanakahi", "of prkdc hanakahi et", "prkdc hanakahi et al.", "hanakahi et al. 2000 .", "et al. 2000 . other", "al. 2000 . other factors", ". other factors such", "other factors such as", "factors such as polynucleotide", "as polynucleotide kinase pnk", "pnk tdp1 or", "tdp1 or tdp2 may remove", "or tdp2 may remove unligatable", "tdp2 may remove unligatable damaged", "may remove unligatable damaged nucleotides", "remove unligatable damaged nucleotides from", "unligatable damaged nucleotides from 5'", "nucleotides from 5' and", "from 5' and 3'", "5' and 3' ends", "and 3' ends of the", "3' ends of the dsb", "of the dsb converting", "the dsb converting them", "dsb converting them to", "converting them to ligatable substrates", "to ligatable substrates inamdar", "ligatable substrates inamdar et", "substrates inamdar et al.", "et al. 2002 gomez", "al. 2002 gomez herreros", "2002 gomez herreros et", "gomez herreros et al. 2013", "herreros et al. 2013 .", "et al. 2013 . dna", "al. 2013 . dna ligase", "2013 . dna ligase 4", "dna ligase 4 lig4", "4 lig4 in", "lig4 in complex with", "complex with xrcc4 xrcc4:lig4", "xrcc4 xrcc4:lig4 is", "xrcc4:lig4 is recruited to", "is recruited to ligatable dna", "recruited to ligatable dna dsb", "to ligatable dna dsb ends", "ligatable dna dsb ends together", "dna dsb ends together with", "dsb ends together with the", "ends together with the xlf", "with the xlf nhej1", "xlf nhej1 homodimer", "nhej1 homodimer and dna", "homodimer and dna polymerases mu", "dna polymerases mu polm", "mu polm and/or", "poll mcelhinny et", "et al. 2000 hsu", "al. 2000 hsu et", "2000 hsu et al.", "et al. 2002 malu", "al. 2002 malu et", "2002 malu et al.", "et al. 2002 ahnesorg", "al. 2002 ahnesorg et", "2002 ahnesorg et al.", "et al. 2006 mahajan", "al. 2006 mahajan et", "2006 mahajan et al.", "et al. 2002 lee", "al. 2002 lee et", "2002 lee et al.", "et al. 2004 fan", "al. 2004 fan and", "2004 fan and wu", "fan and wu 2004 .", "and wu 2004 . after", "wu 2004 . after poll", "2004 . after poll and/or", ". after poll and/or polm", "after poll and/or polm fill", "poll and/or polm fill 1", "polm fill 1 or", "fill 1 or 2", "1 or 2 nucleotide", "or 2 nucleotide long single", "2 nucleotide long single strand", "nucleotide long single strand gaps", "long single strand gaps at", "single strand gaps at aligned", "strand gaps at aligned dna", "gaps at aligned dna dsb", "at aligned dna dsb ends", "dna dsb ends xrcc4:lig4", "dsb ends xrcc4:lig4 performs", "ends xrcc4:lig4 performs the", "xrcc4:lig4 performs the ligation of", "performs the ligation of broken", "the ligation of broken dna", "ligation of broken dna strands", "broken dna strands thus", "dna strands thus completing", "strands thus completing nhej.", "thus completing nhej. the presence", "completing nhej. the presence of", "nhej. the presence of nhej1", "the presence of nhej1 homodimer", "presence of nhej1 homodimer facilitates", "of nhej1 homodimer facilitates the", "nhej1 homodimer facilitates the ligation", "homodimer facilitates the ligation step", "the ligation step especially", "ligation step especially at", "step especially at mismatched", "especially at mismatched dsb ends", "mismatched dsb ends tsai", "dsb ends tsai et", "ends tsai et al.", "tsai et al. 2007 .", "et al. 2007 . depending", "al. 2007 . depending on", "2007 . depending on other", ". depending on other types", "depending on other types of", "on other types of dna", "other types of dna damage", "types of dna damage present", "of dna damage present at", "dna damage present at dna", "damage present at dna dsbs", "at dna dsbs nhej", "dna dsbs nhej can", "dsbs nhej can result", "nhej can result in error", "can result in error free", "result in error free products", "error free products produce", "free products produce dsdna", "products produce dsdna with", "produce dsdna with microdeletions and/or", "dsdna with microdeletions and/or mismatched", "with microdeletions and/or mismatched bases", "and/or mismatched bases or", "mismatched bases or result", "bases or result in", "result in translocations reviewed", "in translocations reviewed by", "translocations reviewed by povrik", "reviewed by povrik et al.", "by povrik et al. 2012", "povrik et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1081", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5696394", "r hsa", "hsa 5696394", "r hsa 5696394" ] }, { "record_id": "GLY_000594_1_1081", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dna damage", "damage recognition", "recognition in", "in gg", "gg ner", "dna damage recognition", "damage recognition in", "recognition in gg", "in gg ner", "dna damage recognition in", "damage recognition in gg", "recognition in gg ner", "dna damage recognition in gg", "damage recognition in gg ner", "in global", "global genome", "genome nucleotide", "nucleotide excision", "excision repair", "the dna", "damage is", "is recognized", "recognized by", "by two", "two protein", "protein complexes.", "complexes. the", "the first", "first complex", "complex consists", "consists of", "of xpc", "rad23a or", "or rad23b", "and cetn2.", "cetn2. this", "this complex", "complex probes", "probes the", "dna helix", "helix 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2004", "moser et", "al. 2005", "camenisch et", "al. 2009", "oh et", "al. 2011", "2011 .", "in global genome", "global genome nucleotide", "genome nucleotide excision", "nucleotide excision repair", "repair gg", "the dna damage", "dna damage is", "damage is recognized", "is recognized by", "recognized by two", "by two protein", "two protein complexes.", "protein complexes. the", "complexes. the first", "the first complex", "first complex consists", "complex consists of", "consists of xpc", "xpc rad23a", "rad23a or rad23b", "rad23b and", "and cetn2. this", "cetn2. this complex", "this complex probes", "complex probes the", "probes the dna", "the dna helix", "dna helix and", "helix and recognizes", "and recognizes damage", "recognizes damage that", "damage that disrupts", "that disrupts normal", "disrupts normal watson", "normal watson crick", "watson crick base", "crick base pairing", "pairing which", "which results in", "results in binding", "in binding of", "binding of the", "of the xpc:rad23:cetn2", "the xpc:rad23:cetn2 complex", "xpc:rad23:cetn2 complex to", "complex to the", "to the undamaged", "the undamaged dna", "undamaged dna strand.", "dna strand. the", "strand. the second", "the second complex", "second complex is", "complex is a", "is a ubiquitin", "a ubiquitin ligase", "ubiquitin ligase uv", "ligase uv ddb", "uv ddb that", "ddb that consists", "that consists of", "consists of ddb2", "ddb2 ddb1", "ddb1 cul4a", "cul4a or cul4b", "or cul4b and", "cul4b and rbx1.", "and rbx1. the", "rbx1. the uv", "the uv ddb", "uv ddb complex", "ddb complex is", "complex is necessary", "is necessary for", "necessary for the", "for the recognition", "the recognition of", "recognition of uv", "of uv induced", "uv induced dna", "induced dna damage", "dna damage and", "damage and may", "and may contribute", "may contribute to", "contribute to the", "to the retention", "the retention of", "retention of the", "xpc:rad23:cetn2 complex at", "complex at the", "at the dna", "dna damage site.", "damage site. the", "site. the uv", "ddb complex binds", "complex binds the", "binds the damaged", "the damaged dna", "damaged dna strand", "strand fitch", "fitch et al.", "et al. 2003", "2003 wang", "wang et al.", "et al. 2004", "2004 moser", "moser et al.", "et al. 2005", "2005 camenisch", "camenisch et al.", "et al. 2009", "2009 oh", "oh et al.", "et al. 2011", "al. 2011 .", "in global genome nucleotide", "global genome nucleotide excision", "genome nucleotide excision repair", "excision repair gg", "repair gg ner", "ner the", "the dna damage is", "dna damage is recognized", "damage is recognized by", "is recognized by two", "recognized by two protein", "by two protein complexes.", "two protein complexes. the", "protein complexes. the first", "complexes. the first complex", "the first complex consists", "first complex consists of", "complex consists of xpc", "of xpc rad23a", "xpc rad23a or", "or rad23b and", "rad23b and cetn2.", "and cetn2. this complex", "cetn2. this complex probes", "this complex probes the", "complex probes the dna", "probes the dna helix", "the dna helix and", "dna helix and recognizes", "helix and recognizes damage", "and recognizes damage that", "recognizes damage that disrupts", "damage that disrupts normal", "that disrupts normal watson", "disrupts normal watson crick", "normal watson crick base", "watson crick base pairing", "base pairing which", "pairing which results", "which results in binding", "results in binding of", "in binding of the", "binding of the xpc:rad23:cetn2", "of the xpc:rad23:cetn2 complex", "the xpc:rad23:cetn2 complex to", "xpc:rad23:cetn2 complex to the", "complex to the undamaged", "to the undamaged dna", "the undamaged dna strand.", "undamaged dna strand. the", "dna strand. the second", "strand. the second complex", "the second complex is", "second complex is a", "complex is a ubiquitin", "is a ubiquitin ligase", "a ubiquitin ligase uv", "ubiquitin ligase uv ddb", "ligase uv ddb that", "uv ddb that consists", "ddb that consists of", "that consists of ddb2", "of ddb2 ddb1", "ddb1 cul4a or", "cul4a or cul4b and", "or cul4b and rbx1.", "cul4b and rbx1. the", "and rbx1. the uv", "rbx1. the uv ddb", "the uv ddb complex", "uv ddb complex is", "ddb complex is necessary", "complex is necessary for", "is necessary for the", "necessary for the recognition", "for the recognition of", "the recognition of uv", "recognition of uv induced", "of uv induced dna", "uv induced dna damage", "induced dna damage and", "dna damage and may", "damage and may contribute", "and may contribute to", "may contribute to the", "contribute to the retention", "to the retention of", "the retention of the", "retention of the xpc:rad23:cetn2", "the xpc:rad23:cetn2 complex at", "xpc:rad23:cetn2 complex at the", "complex at the dna", "at the dna damage", "the dna damage site.", "dna damage site. the", "damage site. the uv", "site. the uv ddb", "uv ddb complex binds", "ddb complex binds the", "complex binds the damaged", "binds the damaged dna", "the damaged dna strand", "dna strand fitch", "strand fitch et", "fitch et al. 2003", "al. 2003 wang", "2003 wang et", "wang et al. 2004", "al. 2004 moser", "2004 moser et", "moser et al. 2005", "al. 2005 camenisch", "2005 camenisch et", "camenisch et al. 2009", "al. 2009 oh", "2009 oh et", "oh et al. 2011", "et al. 2011 .", "in global genome nucleotide excision", "global genome nucleotide excision repair", "nucleotide excision repair gg", "excision repair gg ner", "gg ner the", "ner the dna", "the dna damage is recognized", "dna damage is recognized by", "damage is recognized by two", "is recognized by two protein", "recognized by two protein complexes.", "by two protein complexes. the", "two protein complexes. the first", "protein complexes. the first complex", "complexes. the first complex consists", "the first complex consists of", "first complex consists of xpc", "consists of xpc rad23a", "of xpc rad23a or", "xpc rad23a or rad23b", "rad23a or rad23b and", "or rad23b and cetn2.", "rad23b and cetn2. this", "and cetn2. this complex probes", "cetn2. this complex probes the", "this complex probes the dna", "complex probes the dna helix", "probes the dna helix and", "the dna helix and recognizes", "dna helix and recognizes damage", "helix and recognizes damage that", "and recognizes damage that disrupts", "recognizes damage that disrupts normal", "damage that disrupts normal watson", "that disrupts normal watson crick", "disrupts normal watson crick base", "normal watson crick base pairing", "crick base pairing which", "base pairing which results", "pairing which results in", "which results in binding of", "results in binding of the", "in binding of the xpc:rad23:cetn2", "binding of the xpc:rad23:cetn2 complex", "of the xpc:rad23:cetn2 complex to", "the xpc:rad23:cetn2 complex to the", "xpc:rad23:cetn2 complex to the undamaged", "complex to the undamaged dna", "to the undamaged dna strand.", "the undamaged dna strand. the", "undamaged dna strand. the second", "dna strand. the second complex", "strand. the second complex is", "the second complex is a", "second complex is a ubiquitin", "complex is a ubiquitin ligase", "is a ubiquitin ligase uv", "a ubiquitin ligase uv ddb", "ubiquitin ligase uv ddb that", "ligase uv ddb that consists", "uv ddb that consists of", "ddb that consists of ddb2", "consists of ddb2 ddb1", "ddb2 ddb1 cul4a", "ddb1 cul4a or cul4b", "cul4a or cul4b and rbx1.", "or cul4b and rbx1. the", "cul4b and rbx1. the uv", "and rbx1. the uv ddb", "rbx1. the uv ddb complex", "the uv ddb complex is", "uv ddb complex is necessary", "ddb complex is necessary for", "complex is necessary for the", "is necessary for the recognition", "necessary for the recognition of", "for the recognition of uv", "the recognition of uv induced", "recognition of uv induced dna", "of uv induced dna damage", "uv induced dna damage and", "induced dna damage and may", "dna damage and may contribute", "damage and may contribute to", "and may contribute to the", "may contribute to the retention", "contribute to the retention of", "to the retention of the", "the retention of the xpc:rad23:cetn2", "retention of the xpc:rad23:cetn2 complex", "of the xpc:rad23:cetn2 complex at", "the xpc:rad23:cetn2 complex at the", "xpc:rad23:cetn2 complex at the dna", "complex at the dna damage", "at the dna damage site.", "the dna damage site. the", "dna damage site. the uv", "damage site. the uv ddb", "site. the uv ddb complex", "the uv ddb complex binds", "uv ddb complex binds the", "ddb complex binds the damaged", "complex binds the damaged dna", "binds the damaged dna strand", "damaged dna strand fitch", "dna strand fitch et", "strand fitch et al.", "et al. 2003 wang", "al. 2003 wang et", "2003 wang et al.", "et al. 2004 moser", "al. 2004 moser et", "2004 moser et al.", "et al. 2005 camenisch", "al. 2005 camenisch et", "2005 camenisch et al.", "et al. 2009 oh", "al. 2009 oh et", "2009 oh et al.", "oh et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1082", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5696395", "r hsa", "hsa 5696395", "r hsa 5696395" ] }, { "record_id": "GLY_000594_1_1082", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of incision", "incision complex", "complex in", "in gg", "gg ner", "formation of incision", "of incision complex", "incision complex in", "complex in gg", "in gg ner", "formation of incision complex", "of incision complex in", "incision complex in gg", "complex in gg ner", "formation of incision complex in", "of incision complex in gg", "incision complex in gg ner", "after the", "the xpc", "xpc complex", "complex and", "and the", "the uv", "uv ddb", "ddb complex", "complex bind", "bind damaged", "damaged dna", "a basal", "basal transcription", "transcription factor", "factor tfiih", "tfiih is", "is recruited", "recruited to", "to the", "the nucleotide", "nucleotide excision", "excision repair", "volker et", "et al.", "al. 2001", "riedl et", "al. 2003", "2003 .", ". dna", "dna helicases", "helicases ercc2", "and ercc3", "are subunits", "subunits of", "of the", "the tfiih", "tfiih complex.", "complex. ercc2", "ercc2 unwinds", "unwinds the", "the dna", "dna around", "around the", "the damage", "damage in", "in concert", "concert with", "with the", "the atpase", "atpase activity", "activity of", "of ercc3", "creating an", "an open", "open bubble", "coin et", "al. 2007", "2007 .", ". simultaneously", "the presence", "presence of", "damage is", "is verified", "verified by", "by xpa", "camenisch et", "al. 2006", "2006 .", ". the", "the recruitment", "recruitment of", "of xpa", "xpa is", "is partially", "partially regulated", "regulated by", "by parp1", "parp1 and/or", "and/or parp2", "king et", "al. 2012", "2012 .

              two", ".

              two dna", "dna endonucleases", "the complex", "complex of", "of ercc1", "ercc1 and", "and ercc4", "are recruited", "the open", "bubble structure", "structure to", "to form", "form the", "the incision", "complex that", "that will", "will excise", "excise the", "the damaged", "damaged oligonucleotide", "oligonucleotide from", "from the", "the affected", "affected dna", "dna strand", "dunand sauthier", "sauthier et", "al. 2005", "zotter et", "tsodikov et", "orelli et", "al. 2010", "2010 .", "the rpa", "rpa heterotrimer", "heterotrimer coats", "coats the", "the undamaged", "undamaged dna", "thus protecting", "protecting it", "it from", "the endonucleolytic", "endonucleolytic attack", "de laat", "laat et", "al. 1998", "1998 .", "after the xpc", "the xpc complex", "xpc complex and", "complex and the", "and the uv", "the uv ddb", "uv ddb complex", "ddb complex bind", "complex bind damaged", "bind damaged dna", "dna a", "a basal transcription", "basal transcription factor", "transcription factor tfiih", "factor tfiih is", "tfiih is recruited", "is recruited to", "recruited to the", "to the nucleotide", "the nucleotide excision", "nucleotide excision repair", "repair ner", "ner site", "site volker", "volker et al.", "et al. 2001", "2001 riedl", "riedl et al.", "et al. 2003", "al. 2003 .", "2003 . dna", ". dna helicases", "dna helicases ercc2", "ercc2 xpd", "xpd and", "ercc3 xpb", "xpb are", "are subunits of", "subunits of the", "of the tfiih", "the tfiih complex.", "tfiih complex. ercc2", "complex. ercc2 unwinds", "ercc2 unwinds the", "unwinds the dna", "the dna around", "dna around the", "around the damage", "the damage in", "damage in concert", "in concert with", "concert with the", "with the atpase", "the atpase activity", "atpase activity of", "activity of ercc3", "ercc3 creating", "creating an open", "an open bubble", "bubble coin", "coin et al.", "et al. 2007", "al. 2007 .", "2007 . simultaneously", "simultaneously the", "the presence of", "presence of the", "of the damage", "the damage is", "damage is verified", "is verified by", "verified by xpa", "xpa camenisch", "camenisch et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the recruitment", "the recruitment of", "recruitment of xpa", "of xpa is", "xpa is partially", "is partially regulated", "partially regulated by", "regulated by parp1", "by parp1 and/or", "parp1 and/or parp2", "parp2 king", "king et al.", "et al. 2012", "al. 2012 .

              two", "2012 .

              two dna", ".

              two dna endonucleases", "endonucleases ercc5", "ercc5 xpg", "xpg and", "and the complex", "the complex of", "complex of ercc1", "of ercc1 and", "ercc1 and ercc4", "ercc4 xpf", "are recruited to", "to the open", "the open bubble", "open bubble structure", "bubble structure to", "structure to form", "to form the", "form the incision", "the incision complex", "incision complex that", "complex that will", "that will excise", "will excise the", "excise the damaged", "the damaged oligonucleotide", "damaged oligonucleotide from", "oligonucleotide from the", "from the affected", "the affected dna", "affected dna strand", "strand dunand", "dunand sauthier et", "sauthier et al.", "et al. 2005", "2005 zotter", "zotter et al.", "2006 riedl", "2003 tsodikov", "tsodikov et al.", "2007 orelli", "orelli et al.", "et al. 2010", "al. 2010 .", "2010 . the", ". the rpa", "the rpa heterotrimer", "rpa heterotrimer coats", "heterotrimer coats the", "coats the undamaged", "the undamaged dna", "undamaged dna strand", "strand thus", "thus protecting it", "protecting it from", "it from the", "from the endonucleolytic", "the endonucleolytic attack", "attack de", "de laat et", "laat et al.", "et al. 1998", "al. 1998 .", "after the xpc complex", "the xpc complex and", "xpc complex and the", "complex and the uv", "and the uv ddb", "the uv ddb complex", "uv ddb complex bind", "ddb complex bind damaged", "complex bind damaged dna", "damaged dna a", "dna a basal", "a basal transcription factor", "basal transcription factor tfiih", "transcription factor tfiih is", "factor tfiih is recruited", "tfiih is recruited to", "is recruited to the", "recruited to the nucleotide", "to the nucleotide excision", "the nucleotide excision repair", "excision repair ner", "site volker et", "volker et al. 2001", "al. 2001 riedl", "2001 riedl et", "riedl et al. 2003", "et al. 2003 .", "al. 2003 . dna", "2003 . dna helicases", ". dna helicases ercc2", "helicases ercc2 xpd", "xpd and ercc3", "and ercc3 xpb", "xpb are subunits", "are subunits of the", "subunits of the tfiih", "of the tfiih complex.", "the tfiih complex. ercc2", "tfiih complex. ercc2 unwinds", "complex. ercc2 unwinds the", "ercc2 unwinds the dna", "unwinds the dna around", "the dna around the", "dna around the damage", "around the damage in", "the damage in concert", "damage in concert with", "in concert with the", "concert with the atpase", "with the atpase activity", "the atpase activity of", "atpase activity of ercc3", "of ercc3 creating", "ercc3 creating an", "creating an open bubble", "open bubble coin", "bubble coin et", "coin et al. 2007", "et al. 2007 .", "al. 2007 . simultaneously", ". simultaneously the", "simultaneously the presence", "the presence of the", "presence of the damage", "of the damage is", "the damage is verified", "damage is verified by", "is verified by xpa", "by xpa camenisch", "xpa camenisch et", "camenisch et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the recruitment", ". the recruitment of", "the recruitment of xpa", "recruitment of xpa is", "of xpa is partially", "xpa is partially regulated", "is partially regulated by", "partially regulated by parp1", "regulated by parp1 and/or", "by parp1 and/or parp2", "and/or parp2 king", "parp2 king et", "king et al. 2012", "et al. 2012 .

              two", "al. 2012 .

              two dna", "2012 .

              two dna endonucleases", "dna endonucleases ercc5", "xpg and the", "and the complex of", "the complex of ercc1", "complex of ercc1 and", "of ercc1 and ercc4", "and ercc4 xpf", "xpf are", "are recruited to the", "recruited to the open", "to the open bubble", "the open bubble structure", "open bubble structure to", "bubble structure to form", "structure to form the", "to form the incision", "form the incision complex", "the incision complex that", "incision complex that will", "complex that will excise", "that will excise the", "will excise the damaged", "excise the damaged oligonucleotide", "the damaged oligonucleotide from", "damaged oligonucleotide from the", "oligonucleotide from the affected", "from the affected dna", "the affected dna strand", "dna strand dunand", "strand dunand sauthier", "dunand sauthier et al.", "sauthier et al. 2005", "al. 2005 zotter", "2005 zotter et", "zotter et al. 2006", "al. 2006 riedl", "2006 riedl et", "al. 2003 tsodikov", "2003 tsodikov et", "tsodikov et al. 2007", "al. 2007 orelli", "2007 orelli et", "orelli et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the rpa", ". the rpa heterotrimer", "the rpa heterotrimer coats", "rpa heterotrimer coats the", "heterotrimer coats the undamaged", "coats the undamaged dna", "the undamaged dna strand", "dna strand thus", "strand thus protecting", "thus protecting it from", "protecting it from the", "it from the endonucleolytic", "from the endonucleolytic attack", "endonucleolytic attack de", "attack de laat", "de laat et al.", "laat et al. 1998", "et al. 1998 .", "after the xpc complex and", "the xpc complex and the", "xpc complex and the uv", "complex and the uv ddb", "and the uv ddb complex", "the uv ddb complex bind", "uv ddb complex bind damaged", "ddb complex bind damaged dna", "bind damaged dna a", "damaged dna a basal", "dna a basal transcription", "a basal transcription factor tfiih", "basal transcription factor tfiih is", "transcription factor tfiih is recruited", "factor tfiih is recruited to", "tfiih is recruited to the", "is recruited to the nucleotide", "recruited to the nucleotide excision", "to the nucleotide excision repair", "nucleotide excision repair ner", "repair ner site", "ner site volker", "site volker et al.", "et al. 2001 riedl", "al. 2001 riedl et", "2001 riedl et al.", "riedl et al. 2003 .", "et al. 2003 . dna", "al. 2003 . dna helicases", "2003 . dna helicases ercc2", "dna helicases ercc2 xpd", "ercc2 xpd and", "ercc3 xpb are", "xpb are subunits of", "are subunits of the tfiih", "subunits of the tfiih complex.", "of the tfiih complex. ercc2", "the tfiih complex. ercc2 unwinds", "tfiih complex. ercc2 unwinds the", "complex. ercc2 unwinds the dna", "ercc2 unwinds the dna around", "unwinds the dna around the", "the dna around the damage", "dna around the damage in", "around the damage in concert", "the damage in concert with", "damage in concert with the", "in concert with the atpase", "concert with the atpase activity", "with the atpase activity of", "the atpase activity of ercc3", "activity of ercc3 creating", "of ercc3 creating an", "ercc3 creating an open", "an open bubble coin", "open bubble coin et", "bubble coin et al.", "coin et al. 2007 .", "et al. 2007 . simultaneously", "2007 . simultaneously the", ". simultaneously the presence", "simultaneously the presence of", "the presence of the damage", "presence of the damage is", "of the damage is verified", "the damage is verified by", "damage is verified by xpa", "verified by xpa camenisch", "by xpa camenisch et", "xpa camenisch et al.", "camenisch et al. 2006 .", "et al. 2006 . the", "al. 2006 . the recruitment", "2006 . the recruitment of", ". the recruitment of xpa", "the recruitment of xpa is", "recruitment of xpa is partially", "of xpa is partially regulated", "xpa is partially regulated by", "is partially regulated by parp1", "partially regulated by parp1 and/or", "regulated by parp1 and/or parp2", "parp1 and/or parp2 king", "and/or parp2 king et", "parp2 king et al.", "king et al. 2012 .

              two", "et al. 2012 .

              two dna", "al. 2012 .

              two dna endonucleases", ".

              two dna endonucleases ercc5", "endonucleases ercc5 xpg", "ercc5 xpg and", "xpg and the complex", "and the complex of ercc1", "the complex of ercc1 and", "complex of ercc1 and ercc4", "ercc1 and ercc4 xpf", "xpf are recruited", "are recruited to the open", "recruited to the open bubble", "to the open bubble structure", "the open bubble structure to", "open bubble structure to form", "bubble structure to form the", "structure to form the incision", "to form the incision complex", "form the incision complex that", "the incision complex that will", "incision complex that will excise", "complex that will excise the", "that will excise the damaged", "will excise the damaged oligonucleotide", "excise the damaged oligonucleotide from", "the damaged oligonucleotide from the", "damaged oligonucleotide from the affected", "oligonucleotide from the affected dna", "from the affected dna strand", "affected dna strand dunand", "dna strand dunand sauthier", "strand dunand sauthier et", "dunand sauthier et al. 2005", "et al. 2005 zotter", "al. 2005 zotter et", "2005 zotter et al.", "et al. 2006 riedl", "al. 2006 riedl et", "2006 riedl et al.", "et al. 2003 tsodikov", "al. 2003 tsodikov et", "2003 tsodikov et al.", "et al. 2007 orelli", "al. 2007 orelli et", "2007 orelli et al.", "orelli et al. 2010 .", "et al. 2010 . the", "al. 2010 . the rpa", "2010 . the rpa heterotrimer", ". the rpa heterotrimer coats", "the rpa heterotrimer coats the", "rpa heterotrimer coats the undamaged", "heterotrimer coats the undamaged dna", "coats the undamaged dna strand", "undamaged dna strand thus", "dna strand thus protecting", "strand thus protecting it", "thus protecting it from the", "protecting it from the endonucleolytic", "it from the endonucleolytic attack", "the endonucleolytic attack de", "endonucleolytic attack de laat", "attack de laat et", "de laat et al. 1998", "laat et al. 1998 ." ] }, { "record_id": "GLY_000594_1_1083", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6781823", "r hsa", "hsa 6781823", "r hsa 6781823" ] }, { "record_id": "GLY_000594_1_1083", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of tc", "tc ner", "ner pre", "pre incision", "incision complex", "formation of tc", "of tc ner", "tc ner pre", "ner pre incision", "pre incision complex", "formation of tc ner", "of tc ner pre", "tc ner pre incision", "ner pre incision complex", "formation of tc ner pre", "of tc ner pre incision", "tc ner pre incision complex", "complex is", "is initiated", "initiated when", "when the", "the rna", "rna polymerase", "polymerase ii", "rna pol", "pol ii", "complex stalls", "stalls at", "at a", "a dna", "dna damage", "damage site.", "site. the", "the stalling", "stalling is", "is caused", "caused by", "by misincorporation", "misincorporation of", "of a", "a ribonucleotide", "ribonucleotide opposite", "opposite to", "to a", "a damaged", "damaged base", "brueckner et", "et al.", "al. 2007", "2007 .", ". cockayne", "cockayne syndrome", "syndrome protein", "protein b", "binds stalled", "stalled rna", "ii and", "and recruits", "recruits cockayne", "protein a", "csa .", ". ercc8", "ercc8 is", "is part", "part of", "of an", "an ubiquitin", "ubiquitin ligase", "ligase complex", "complex that", "that also", "also contains", "contains ddb1", "cul4a or", "or cul4b", "cul4b and", "and rbx1.", "rbx1. this", "this complex", "is implicated", "implicated in", "in the", "the regulation", "regulation of", "ner progression", "progression probably", "probably by", "by ubiquitinating", "ubiquitinating one", "one or", "or more", "more factors", "factors involved", "involved in", "in this", "this pathway", "which may", "may include", "include rna", "and ercc6", "ercc6 at", "at the", "the later", "later stages", "stages of", "of repair", "bregman et", "al. 1996", "fousteri et", "al. 2006", "groisman et", "2006 .", ". xpa", "xpa is", "is recruited", "recruited to", "to the", "the tc", "ner site", "site through", "through its", "its interaction", "interaction with", "with the", "the tfiih", "tfiih complex", "furuta et", "al. 2002", "ziani et", "al. 2014", "2014 .", ". the", "the xab2", "xab2 complex", "which probably", "probably regulates", "regulates the", "the accessibility", "accessibility of", "of the", "the dna", "damage site", "its rna", "rna dna", "dna helicase", "helicase activity", "binds the", "site via", "via the", "the interaction", "interaction of", "of its", "its xab2", "xab2 subunit", "subunit with", "with rna", "ercc8 and", "and xpa", "nakatsu et", "al. 2000", "sollier et", ". tcea1", "is a", "a transcription", "transcription elongation", "elongation factor", "factor that", "that may", "may facilitate", "facilitate backtracking", "backtracking of", "the stalled", "enabling access", "access of", "repair proteins", "proteins to", "site and", "and promotes", "promotes partial", "partial digestion", "digestion of", "the 3'", "3' protruding", "protruding end", "end of", "the nascent", "nascent mrna", "mrna transcript", "transcript by", "by the", "the backtracked", "backtracked rna", "allowing resumption", "resumption of", "of rna", "rna synthesis", "synthesis after", "after damage", "damage removal", "donahue et", "al. 1994", "1994 .", ". access", "access to", "to dna", "damage sites", "sites in", "in tc", "ner was", "was suggested", "suggested to", "to be", "be facilitated", "facilitated by", "by a", "a chromatin", "chromatin remodeler", "remodeler hmgn1", "birger et", "al. 2003", "but another", "another sudy", "sudy found", "found that", "that hmgn1", "hmgn1 was", "was not", "not needed", "needed for", "for human", "human tc", "apelt et", "al. 2020", "2020 .", ". uvssa", "uvssa protein", "protein interacts", "interacts with", "with ubiquitinated", "ubiquitinated ercc6", "ercc6 and", "and rna", "recruiting ubiquitin", "ubiquitin protease", "protease usp7", "usp7 to", "and promoting", "promoting ercc6", "ercc6 stabilization", "nakazawa et", "al. 2012", "schwertman et", "zhang et", "fei and", "and chen", "chen 2012", "2012 .", "incision complex is", "complex is initiated", "is initiated when", "initiated when the", "when the rna", "the rna polymerase", "rna polymerase ii", "ii rna", "rna pol ii", "ii complex", "complex stalls at", "stalls at a", "at a dna", "a dna damage", "dna damage site.", "damage site. the", "site. the stalling", "the stalling is", "stalling is caused", "is caused by", "caused by misincorporation", "by misincorporation of", "misincorporation of a", "of a ribonucleotide", "a ribonucleotide opposite", "ribonucleotide opposite to", "opposite to a", "to a damaged", "a damaged base", "base brueckner", "brueckner et al.", "et al. 2007", "al. 2007 .", "2007 . cockayne", ". cockayne syndrome", "cockayne syndrome protein", "syndrome protein b", "b ercc6", "ercc6 csb", "csb binds", "binds stalled rna", "stalled rna pol", "pol ii and", "ii and recruits", "and recruits cockayne", "recruits cockayne syndrome", "syndrome protein a", "a ercc8", "ercc8 csa", "csa . ercc8", ". ercc8 is", "ercc8 is part", "is part of", "part of an", "of an ubiquitin", "an ubiquitin ligase", "ubiquitin ligase complex", "ligase complex that", "complex that also", "that also contains", "also contains ddb1", "ddb1 cul4a", "cul4a or cul4b", "or cul4b and", "cul4b and rbx1.", "and rbx1. this", "rbx1. this complex", "this complex is", "complex is implicated", "is implicated in", "implicated in the", "in the regulation", "the regulation of", "regulation of tc", "tc ner progression", "ner progression probably", "progression probably by", "probably by ubiquitinating", "by ubiquitinating one", "ubiquitinating one or", "one or more", "or more factors", "more factors involved", "factors involved in", "involved in this", "in this pathway", "pathway which", "which may include", "may include rna", "include rna pol", "ii and ercc6", "and ercc6 at", "ercc6 at the", "at the later", "the later stages", "later stages of", "stages of repair", "repair bregman", "bregman et al.", "et al. 1996", "1996 fousteri", "fousteri et al.", "et al. 2006", "2006 groisman", "groisman et al.", "al. 2006 .", "2006 . xpa", ". xpa is", "xpa is recruited", "is recruited to", "recruited to the", "to the tc", "the tc ner", "tc ner site", "ner site through", "site through its", "through its interaction", "its interaction with", "interaction with the", "with the tfiih", "the tfiih complex", "complex furuta", "furuta et al.", "et al. 2002", "2002 ziani", "ziani et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the xab2", "the xab2 complex", "complex which", "which probably regulates", "probably regulates the", "regulates the accessibility", "the accessibility of", "accessibility of the", "of the dna", "the dna damage", "dna damage site", "damage site through", "through its rna", "its rna dna", "rna dna helicase", "dna helicase activity", "activity binds", "binds the tc", "ner site via", "site via the", "via the interaction", "the interaction of", "interaction of its", "of its xab2", "its xab2 subunit", "xab2 subunit with", "subunit with rna", "with rna pol", "ii ercc6", "ercc6 ercc8", "ercc8 and xpa", "xpa nakatsu", "nakatsu et al.", "et al. 2000", "2000 sollier", "sollier et al.", "2014 . tcea1", "tcea1 tfiis", "tfiis is", "is a transcription", "a transcription elongation", "transcription elongation factor", "elongation factor that", "factor that may", "that may facilitate", "may facilitate backtracking", "facilitate backtracking of", "backtracking of the", "of the stalled", "the stalled rna", "ii enabling", "enabling access of", "access of repair", "of repair proteins", "repair proteins to", "proteins to the", "to the dna", "damage site and", "site and promotes", "and promotes partial", "promotes partial digestion", "partial digestion of", "digestion of the", "of the 3'", "the 3' protruding", "3' protruding end", "protruding end of", "end of the", "of the nascent", "the nascent mrna", "nascent mrna transcript", "mrna transcript by", "transcript by the", "by the backtracked", "the backtracked rna", "backtracked rna pol", "ii allowing", "allowing resumption of", "resumption of rna", "of rna synthesis", "rna synthesis after", "synthesis after damage", "after damage removal", "removal donahue", "donahue et al.", "et al. 1994", "al. 1994 .", "1994 . access", ". access to", "access to dna", "to dna damage", "dna damage sites", "damage sites in", "sites in tc", "in tc ner", "tc ner was", "ner was suggested", "was suggested to", "suggested to be", "to be facilitated", "be facilitated by", "facilitated by a", "by a chromatin", "a chromatin remodeler", "chromatin remodeler hmgn1", "hmgn1 birger", "birger et al.", "et al. 2003", "but another sudy", "another sudy found", "sudy found that", "found that hmgn1", "that hmgn1 was", "hmgn1 was not", "was not needed", "not needed for", "needed for human", "for human tc", "human tc ner", "ner apelt", "apelt et al.", "et al. 2020", "al. 2020 .", "2020 . uvssa", ". uvssa protein", "uvssa protein interacts", "protein interacts with", "interacts with ubiquitinated", "with ubiquitinated ercc6", "ubiquitinated ercc6 and", "ercc6 and rna", "and rna pol", "ii recruiting", "recruiting ubiquitin protease", "ubiquitin protease usp7", "protease usp7 to", "usp7 to the", "ner site and", "site and promoting", "and promoting ercc6", "promoting ercc6 stabilization", "stabilization nakazawa", "nakazawa et al.", "et al. 2012", "2012 schwertman", "schwertman et al.", "2012 zhang", "zhang et al.", "2012 fei", "fei and chen", "and chen 2012", "chen 2012 .", "pre incision complex is", "incision complex is initiated", "complex is initiated when", "is initiated when the", "initiated when the rna", "when the rna polymerase", "the rna polymerase ii", "polymerase ii rna", "ii rna pol", "pol ii complex", "ii complex stalls", "complex stalls at a", "stalls at a dna", "at a dna damage", "a dna damage site.", "dna damage site. the", "damage site. the stalling", "site. the stalling is", "the stalling is caused", "stalling is caused by", "is caused by misincorporation", "caused by misincorporation of", "by misincorporation of a", "misincorporation of a ribonucleotide", "of a ribonucleotide opposite", "a ribonucleotide opposite to", "ribonucleotide opposite to a", "opposite to a damaged", "to a damaged base", "damaged base brueckner", "base brueckner et", "brueckner et al. 2007", "et al. 2007 .", "al. 2007 . cockayne", "2007 . cockayne syndrome", ". cockayne syndrome protein", "cockayne syndrome protein b", "protein b ercc6", "csb binds stalled", "binds stalled rna pol", "stalled rna pol ii", "rna pol ii and", "pol ii and recruits", "ii and recruits cockayne", "and recruits cockayne syndrome", "recruits cockayne syndrome protein", "cockayne syndrome protein a", "protein a ercc8", "ercc8 csa .", "csa . ercc8 is", ". ercc8 is part", "ercc8 is part of", "is part of an", "part of an ubiquitin", "of an ubiquitin ligase", "an ubiquitin ligase complex", "ubiquitin ligase complex that", "ligase complex that also", "complex that also contains", "that also contains ddb1", "contains ddb1 cul4a", "ddb1 cul4a or", "cul4a or cul4b and", "or cul4b and rbx1.", "cul4b and rbx1. this", "and rbx1. this complex", "rbx1. this complex is", "this complex is implicated", "complex is implicated in", "is implicated in the", "implicated in the regulation", "in the regulation of", "the regulation of tc", "regulation of tc ner", "of tc ner progression", "tc ner progression probably", "ner progression probably by", "progression probably by ubiquitinating", "probably by ubiquitinating one", "by ubiquitinating one or", "ubiquitinating one or more", "one or more factors", "or more factors involved", "more factors involved in", "factors involved in this", "involved in this pathway", "this pathway which", "pathway which may", "which may include rna", "may include rna pol", "include rna pol ii", "pol ii and ercc6", "ii and ercc6 at", "and ercc6 at the", "ercc6 at the later", "at the later stages", "the later stages of", "later stages of repair", "of repair bregman", "repair bregman et", "bregman et al. 1996", "al. 1996 fousteri", "1996 fousteri et", "fousteri et al. 2006", "al. 2006 groisman", "2006 groisman et", "groisman et al. 2006", "et al. 2006 .", "al. 2006 . xpa", "2006 . xpa is", ". xpa is recruited", "xpa is recruited to", "is recruited to the", "recruited to the tc", "to the tc ner", "the tc ner site", "tc ner site through", "ner site through its", "site through its interaction", "through its interaction with", "its interaction with the", "interaction with the tfiih", "with the tfiih complex", "tfiih complex furuta", "complex furuta et", "furuta et al. 2002", "al. 2002 ziani", "2002 ziani et", "ziani et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the xab2", ". the xab2 complex", "xab2 complex which", "complex which probably", "which probably regulates the", "probably regulates the accessibility", "regulates the accessibility of", "the accessibility of the", "accessibility of the dna", "of the dna damage", "the dna damage site", "dna damage site through", "damage site through its", "site through its rna", "through its rna dna", "its rna dna helicase", "rna dna helicase activity", "helicase activity binds", "activity binds the", "binds the tc ner", "tc ner site via", "ner site via the", "site via the interaction", "via the interaction of", "the interaction of its", "interaction of its xab2", "of its xab2 subunit", "its xab2 subunit with", "xab2 subunit with rna", "subunit with rna pol", "with rna pol ii", "pol ii ercc6", "ercc6 ercc8 and", "and xpa nakatsu", "xpa nakatsu et", "nakatsu et al. 2000", "al. 2000 sollier", "2000 sollier et", "sollier et al. 2014", "al. 2014 . tcea1", ". tcea1 tfiis", "tfiis is a", "is a transcription elongation", "a transcription elongation factor", "transcription elongation factor that", "elongation factor that may", "factor that may facilitate", "that may facilitate backtracking", "may facilitate backtracking of", "facilitate backtracking of the", "backtracking of the stalled", "of the stalled rna", "the stalled rna pol", "pol ii enabling", "ii enabling access", "enabling access of repair", "access of repair proteins", "of repair proteins to", "repair proteins to the", "proteins to the dna", "to the dna damage", "dna damage site and", "damage site and promotes", "site and promotes partial", "and promotes partial digestion", "promotes partial digestion of", "partial digestion of the", "digestion of the 3'", "of the 3' protruding", "the 3' protruding end", "3' protruding end of", "protruding end of the", "end of the nascent", "of the nascent mrna", "the nascent mrna transcript", "nascent mrna transcript by", "mrna transcript by the", "transcript by the backtracked", "by the backtracked rna", "the backtracked rna pol", "backtracked rna pol ii", "pol ii allowing", "ii allowing resumption", "allowing resumption of rna", "resumption of rna synthesis", "of rna synthesis after", "rna synthesis after damage", "synthesis after damage removal", "damage removal donahue", "removal donahue et", "donahue et al. 1994", "et al. 1994 .", "al. 1994 . access", "1994 . access to", ". access to dna", "access to dna damage", "to dna damage sites", "dna damage sites in", "damage sites in tc", "sites in tc ner", "in tc ner was", "tc ner was suggested", "ner was suggested to", "was suggested to be", "suggested to be facilitated", "to be facilitated by", "be facilitated by a", "facilitated by a chromatin", "by a chromatin remodeler", "a chromatin remodeler hmgn1", "remodeler hmgn1 birger", "hmgn1 birger et", "birger et al. 2003", "2003 but", "but another sudy found", "another sudy found that", "sudy found that hmgn1", "found that hmgn1 was", "that hmgn1 was not", "hmgn1 was not needed", "was not needed for", "not needed for human", "needed for human tc", "for human tc ner", "tc ner apelt", "ner apelt et", "apelt et al. 2020", "et al. 2020 .", "al. 2020 . uvssa", "2020 . uvssa protein", ". uvssa protein interacts", "uvssa protein interacts with", "protein interacts with ubiquitinated", "interacts with ubiquitinated ercc6", "with ubiquitinated ercc6 and", "ubiquitinated ercc6 and rna", "ercc6 and rna pol", "and rna pol ii", "pol ii recruiting", "ii recruiting ubiquitin", "recruiting ubiquitin protease usp7", "ubiquitin protease usp7 to", "protease usp7 to the", "usp7 to the tc", "tc ner site and", "ner site and promoting", "site and promoting ercc6", "and promoting ercc6 stabilization", "ercc6 stabilization nakazawa", "stabilization nakazawa et", "nakazawa et al. 2012", "al. 2012 schwertman", "2012 schwertman et", "schwertman et al. 2012", "al. 2012 zhang", "2012 zhang et", "zhang et al. 2012", "al. 2012 fei", "2012 fei and", "fei and chen 2012", "and chen 2012 .", "ner pre incision complex is", "pre incision complex is initiated", "incision complex is initiated when", "complex is initiated when the", "is initiated when the rna", "initiated when the rna polymerase", "when the rna polymerase ii", "rna polymerase ii rna", "polymerase ii rna pol", "ii rna pol ii", "rna pol ii complex", "pol ii complex stalls", "ii complex stalls at", "complex stalls at a dna", "stalls at a dna damage", "at a dna damage site.", "a dna damage site. the", "dna damage site. the stalling", "damage site. the stalling is", "site. the stalling is caused", "the stalling is caused by", "stalling is caused by misincorporation", "is caused by misincorporation of", "caused by misincorporation of a", "by misincorporation of a ribonucleotide", "misincorporation of a ribonucleotide opposite", "of a ribonucleotide opposite to", "a ribonucleotide opposite to a", "ribonucleotide opposite to a damaged", "opposite to a damaged base", "a damaged base brueckner", "damaged base brueckner et", "base brueckner et al.", "brueckner et al. 2007 .", "et al. 2007 . cockayne", "al. 2007 . cockayne syndrome", "2007 . cockayne syndrome protein", ". cockayne syndrome protein b", "syndrome protein b ercc6", "b ercc6 csb", "ercc6 csb binds", "csb binds stalled rna", "binds stalled rna pol ii", "stalled rna pol ii and", "rna pol ii and recruits", "pol ii and recruits cockayne", "ii and recruits cockayne syndrome", "and recruits cockayne syndrome protein", "recruits cockayne syndrome protein a", "syndrome protein a ercc8", "a ercc8 csa", "ercc8 csa . ercc8", "csa . ercc8 is part", ". ercc8 is part of", "ercc8 is part of an", "is part of an ubiquitin", "part of an ubiquitin ligase", "of an ubiquitin ligase complex", "an ubiquitin ligase complex that", "ubiquitin ligase complex that also", "ligase complex that also contains", "complex that also contains ddb1", "also contains ddb1 cul4a", "contains ddb1 cul4a or", "ddb1 cul4a or cul4b", "cul4a or cul4b and rbx1.", "or cul4b and rbx1. this", "cul4b and rbx1. this complex", "and rbx1. this complex is", "rbx1. this complex is implicated", "this complex is implicated in", "complex is implicated in the", "is implicated in the regulation", "implicated in the regulation of", "in the regulation of tc", "the regulation of tc ner", "regulation of tc ner progression", "of tc ner progression probably", "tc ner progression probably by", "ner progression probably by ubiquitinating", "progression probably by ubiquitinating one", "probably by ubiquitinating one or", "by ubiquitinating one or more", "ubiquitinating one or more factors", "one or more factors involved", "or more factors involved in", "more factors involved in this", "factors involved in this pathway", "in this pathway which", "this pathway which may", "pathway which may include", "which may include rna pol", "may include rna pol ii", "include rna pol ii and", "rna pol ii and ercc6", "pol ii and ercc6 at", "ii and ercc6 at the", "and ercc6 at the later", "ercc6 at the later stages", "at the later stages of", "the later stages of repair", "stages of repair bregman", "of repair bregman et", "repair bregman et al.", "et al. 1996 fousteri", "al. 1996 fousteri et", "1996 fousteri et al.", "et al. 2006 groisman", "al. 2006 groisman et", "2006 groisman et al.", "groisman et al. 2006 .", "et al. 2006 . xpa", "al. 2006 . xpa is", "2006 . xpa is recruited", ". xpa is recruited to", "xpa is recruited to the", "is recruited to the tc", "recruited to the tc ner", "to the tc ner site", "the tc ner site through", "tc ner site through its", "ner site through its interaction", "site through its interaction with", "through its interaction with the", "its interaction with the tfiih", "interaction with the tfiih complex", "the tfiih complex furuta", "tfiih complex furuta et", "complex furuta et al.", "et al. 2002 ziani", "al. 2002 ziani et", "2002 ziani et al.", "ziani et al. 2014 .", "et al. 2014 . the", "al. 2014 . the xab2", "2014 . the xab2 complex", "the xab2 complex which", "xab2 complex which probably", "complex which probably regulates", "which probably regulates the accessibility", "probably regulates the accessibility of", "regulates the accessibility of the", "the accessibility of the dna", "accessibility of the dna damage", "of the dna damage site", "the dna damage site through", "dna damage site through its", "damage site through its rna", "site through its rna dna", "through its rna dna helicase", "its rna dna helicase activity", "dna helicase activity binds", "helicase activity binds the", "activity binds the tc", "binds the tc ner site", "the tc ner site via", "tc ner site via the", "ner site via the interaction", "site via the interaction of", "via the interaction of its", "the interaction of its xab2", "interaction of its xab2 subunit", "of its xab2 subunit with", "its xab2 subunit with rna", "xab2 subunit with rna pol", "subunit with rna pol ii", "rna pol ii ercc6", "ii ercc6 ercc8", "ercc6 ercc8 and xpa", "ercc8 and xpa nakatsu", "and xpa nakatsu et", "xpa nakatsu et al.", "et al. 2000 sollier", "al. 2000 sollier et", "2000 sollier et al.", "sollier et al. 2014 .", "et al. 2014 . tcea1", "2014 . tcea1 tfiis", "tcea1 tfiis is", "tfiis is a transcription", "is a transcription elongation factor", "a transcription elongation factor that", "transcription elongation factor that may", "elongation factor that may facilitate", "factor that may facilitate backtracking", "that may facilitate backtracking of", "may facilitate backtracking of the", "facilitate backtracking of the stalled", "backtracking of the stalled rna", "of the stalled rna pol", "the stalled rna pol ii", "rna pol ii enabling", "pol ii enabling access", "ii enabling access of", "enabling access of repair proteins", "access of repair proteins to", "of repair proteins to the", "repair proteins to the dna", "proteins to the dna damage", "to the dna damage site", "the dna damage site and", "dna damage site and promotes", "damage site and promotes partial", "site and promotes partial digestion", "and promotes partial digestion of", "promotes partial digestion of the", "partial digestion of the 3'", "digestion of the 3' protruding", "of the 3' protruding end", "the 3' protruding end of", "3' protruding end of the", "protruding end of the nascent", "end of the nascent mrna", "of the nascent mrna transcript", "the nascent mrna transcript by", "nascent mrna transcript by the", "mrna transcript by the backtracked", "transcript by the backtracked rna", "by the backtracked rna pol", "the backtracked rna pol ii", "rna pol ii allowing", "pol ii allowing resumption", "ii allowing resumption of", "allowing resumption of rna synthesis", "resumption of rna synthesis after", "of rna synthesis after damage", "rna synthesis after damage removal", "after damage removal donahue", "damage removal donahue et", "removal donahue et al.", "donahue et al. 1994 .", "et al. 1994 . access", "al. 1994 . access to", "1994 . access to dna", ". access to dna damage", "access to dna damage sites", "to dna damage sites in", "dna damage sites in tc", "damage sites in tc ner", "sites in tc ner was", "in tc ner was suggested", "tc ner was suggested to", "ner was suggested to be", "was suggested to be facilitated", "suggested to be facilitated by", "to be facilitated by a", "be facilitated by a chromatin", "facilitated by a chromatin remodeler", "by a chromatin remodeler hmgn1", "chromatin remodeler hmgn1 birger", "remodeler hmgn1 birger et", "hmgn1 birger et al.", "al. 2003 but", "2003 but another", "but another sudy found that", "another sudy found that hmgn1", "sudy found that hmgn1 was", "found that hmgn1 was not", "that hmgn1 was not needed", "hmgn1 was not needed for", "was not needed for human", "not needed for human tc", "needed for human tc ner", "human tc ner apelt", "tc ner apelt et", "ner apelt et al.", "apelt et al. 2020 .", "et al. 2020 . uvssa", "al. 2020 . uvssa protein", "2020 . uvssa protein interacts", ". uvssa protein interacts with", "uvssa protein interacts with ubiquitinated", "protein interacts with ubiquitinated ercc6", "interacts with ubiquitinated ercc6 and", "with ubiquitinated ercc6 and rna", "ubiquitinated ercc6 and rna pol", "ercc6 and rna pol ii", "rna pol ii recruiting", "pol ii recruiting ubiquitin", "ii recruiting ubiquitin protease", "recruiting ubiquitin protease usp7 to", "ubiquitin protease usp7 to the", "protease usp7 to the tc", "usp7 to the tc ner", "the tc ner site and", "tc ner site and promoting", "ner site and promoting ercc6", "site and promoting ercc6 stabilization", "promoting ercc6 stabilization nakazawa", "ercc6 stabilization nakazawa et", "stabilization nakazawa et al.", "et al. 2012 schwertman", "al. 2012 schwertman et", "2012 schwertman et al.", "et al. 2012 zhang", "al. 2012 zhang et", "2012 zhang et al.", "et al. 2012 fei", "al. 2012 fei and", "2012 fei and chen", "fei and chen 2012 ." ] }, { "record_id": "GLY_000594_1_1084", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6781827", "r hsa", "hsa 6781827", "r hsa 6781827" ] }, { "record_id": "GLY_000594_1_1084", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcription coupled", "coupled nucleotide", "nucleotide excision", "excision repair", "tc ner", "transcription coupled nucleotide", "coupled nucleotide excision", "nucleotide excision repair", "repair tc", "transcription coupled nucleotide excision", "coupled nucleotide excision repair", "excision repair tc", "repair tc ner", "transcription coupled nucleotide excision repair", "nucleotide excision repair tc", "excision repair tc ner", "dna damage", "damage in", "in transcribed", "transcribed strands", "strands of", "of active", "active genes", "genes is", "is repaired", "repaired through", "through a", "a specialized", "specialized nucleotide", "pathway known", "known as", "as transcription", "ner .", ". tc", "ner impairment", "impairment is", "is the", "the underlying", "underlying cause", "cause of", "of a", "a severe", "severe hereditary", "hereditary disorder", "disorder cockayne", "cockayne syndrome", "an autosomal", "autosomal recessive", "recessive disease", "disease characterized", "characterized by", "by hypersensitivity", "hypersensitivity to", "to uv", "uv light.
              tc", "light.
              tc ner", "ner is", "is triggered", "triggered by", "by helix", "helix distorting", "distorting lesions", "lesions that", "that block", "block the", "the progression", "progression of", "of elongating", "elongating rna", "rna polymerase", "polymerase ii", "rna pol", "pol ii", "ii .", ". stalled", "stalled rna", "ii complex", "complex triggers", "triggers the", "the recruitment", "recruitment of", "of ercc6.", "ercc6. ercc6", "commonly known", "as csb", "syndrome protein", "protein b", "recruits ercc8", "as csa", "protein a", "a .", ". ercc8", "ercc8 has", "has 7", "7 wd", "wd repeat", "repeat motifs", "motifs and", "and is", "is part", "part of", "of the", "the ubiquitin", "ubiquitin ligase", "ligase complex", "complex that", "that also", "also includes", "includes ddb1", "cul4a or", "or cul4b", "cul4b and", "and rbx1.", "rbx1. the", "the ercc8", "ercc8 ubiquitin", "complex is", "is one", "one of", "the key", "key regulators", "regulators of", "of tc", "ner that", "that probably", "probably exerts", "exerts its", "its role", "role by", "by ubiquitinating", "ubiquitinating one", "one or", "or more", "more factors", "factors involved", "involved in", "in this", "this repair", "repair process", "including the", "the rna", "complex and", "and ercc6.
              in", "ercc6.
              in addition", "addition to", "to rna", "ercc6 and", "and the", "ercc8 complex", "the transcription", "transcription elongation", "elongation factor", "factor tfiih", "which is", "is also", "also involved", "in global", "global genome", "genome nucleotide", "gg ner", "is recruited", "recruited to", "to sites", "sites of", "tc ner.", "ner. the", "the tc", "ner pre", "pre incision", "incision complex", "complex also", "includes xpa", "xab2 complex", "uvssa in", "in complex", "complex with", "with usp7", "and ep300", "p300 .", ". xpa", "xpa probably", "probably contributes", "contributes to", "to the", "the assembly", "assembly and", "and stability", "stability of", "the pre", "similar to", "to its", "role in", "in gg", "gg ner.", "the xab2", "is involved", "in pre", "pre mrna", "mrna splicing", "splicing and", "and may", "may modulate", "modulate the", "the structure", "structure of", "the nascent", "nascent mrna", "mrna hybrid", "hybrid with", "with template", "template dna", "dna through", "through its", "its rna", "rna dna", "dna helicase", "helicase activity", "allowing proper", "proper processing", "processing of", "of dna", "dna damage.", "damage. tcea1", "tcea1 may", "may be", "be involved", "in rna", "ii backtracking", "which allows", "allows repair", "repair proteins", "proteins to", "to gain", "gain access", "access to", "the damage", "damage site.", "site. it", "it also", "also facilitates", "facilitates trimming", "trimming of", "the 3'", "3' end", "end of", "of protruding", "protruding nascent", "mrna from", "from the", "the stalled", "enabling recovery", "recovery of", "of rna", "rna synthesis", "synthesis after", "after repair.

              deubiquitinating", "repair.

              deubiquitinating activity", "activity of", "the uvssa:usp7", "uvssa:usp7 complex", "is needed", "needed for", "for ercc6", "ercc6 stability", "stability at", "at repair", "repair sites.", "sites. non", "non histone", "histone nucleosomal", "nucleosomal binding", "binding protein", "protein hmgn1", "hmgn1 and", "and histone", "histone acetyltransferase", "acetyltransferase p300", "remodel the", "the chromatin", "chromatin around", "around the", "the damaged", "damaged site", "thus facilitating", "facilitating repair.

              dual", "repair.

              dual incision", "incision of", "the lesion", "lesion containing", "containing oligonucleotide", "oligonucleotide from", "the affected", "affected dna", "dna strand", "strand is", "is performed", "performed by", "by two", "two dna", "dna endonucleases", "the ercc1:ercc4", "and ercc5", "which also", "also participate", "participate in", "ner. dna", "dna polymerases", "polymerases delta", "epsilon or", "or kappa", "kappa fill", "fill in", "in the", "the single", "single stranded", "stranded gap", "gap after", "after dual", "dual incision", "incision and", "the remaining", "remaining single", "single strand", "strand nick", "nick is", "is sealed", "sealed by", "by dna", "dna ligases", "ligases lig1", "lig1 or", "or lig3", "the latter", "latter in", "with xrcc1", "to gg", "ner. after", "after the", "the repair", "repair of", "damage is", "is complete", "ii resumes", "resumes rna", "rna synthesis.
              for", "synthesis.
              for past", "past and", "and recent", "recent reviews", "see mellon", "mellon et", "et al.", "al. 1987", "svejstrup 2002", "hanawalt and", "and spivak", "spivak 2008", "vermeulen and", "and fousteri", "fousteri 2013", "2013 and", "and marteijn", "marteijn et", "al. 2014.", "dna damage in", "damage in transcribed", "in transcribed strands", "transcribed strands of", "strands of active", "of active genes", "active genes is", "genes is repaired", "is repaired through", "repaired through a", "through a specialized", "a specialized nucleotide", "specialized nucleotide excision", "repair ner", "ner pathway", "pathway known as", "known as transcription", "as transcription coupled", "tc ner .", "ner . tc", ". tc ner", "tc ner impairment", "ner impairment is", "impairment is the", "is the underlying", "the underlying cause", "underlying cause of", "cause of a", "of a severe", "a severe hereditary", "severe hereditary disorder", "hereditary disorder cockayne", "disorder cockayne syndrome", "syndrome an", "an autosomal recessive", "autosomal recessive disease", "recessive disease characterized", "disease characterized by", "characterized by hypersensitivity", "by hypersensitivity to", "hypersensitivity to uv", "to uv light.
              tc", "uv light.
              tc ner", "light.
              tc ner is", "ner is triggered", "is triggered by", "triggered by helix", "by helix distorting", "helix distorting lesions", "distorting lesions that", "lesions that block", "that block the", "block the progression", "the progression of", "progression of elongating", "of elongating rna", "elongating rna polymerase", "rna polymerase ii", "ii rna", "rna pol ii", "pol ii .", "ii . stalled", ". stalled rna", "stalled rna pol", "pol ii complex", "ii complex triggers", "complex triggers the", "triggers the recruitment", "the recruitment of", "recruitment of ercc6.", "of ercc6. ercc6", "ercc6 commonly", "commonly known as", "known as csb", "csb cockayne", "cockayne syndrome protein", "syndrome protein b", "b recruits", "ercc8 commonly", "known as csa", "csa cockayne", "syndrome protein a", "protein a .", "a . ercc8", ". ercc8 has", "ercc8 has 7", "has 7 wd", "7 wd repeat", "wd repeat motifs", "repeat motifs and", "motifs and is", "and is part", "is part of", "part of the", "of the ubiquitin", "the ubiquitin ligase", "ubiquitin ligase complex", "ligase complex that", "complex that also", "that also includes", "also includes ddb1", "ddb1 cul4a", "cul4a or cul4b", "or cul4b and", "cul4b and rbx1.", "and rbx1. the", "rbx1. the ercc8", "the ercc8 ubiquitin", "ercc8 ubiquitin ligase", "ligase complex is", "complex is one", "is one of", "one of the", "of the key", "the key regulators", "key regulators of", "regulators of tc", "of tc ner", "tc ner that", "ner that probably", "that probably exerts", "probably exerts its", "exerts its role", "its role by", "role by ubiquitinating", "by ubiquitinating one", "ubiquitinating one or", "one or more", "or more factors", "more factors involved", "factors involved in", "involved in this", "in this repair", "this repair process", "process including", "including the rna", "the rna pol", "ii complex and", "complex and ercc6.
              in", "and ercc6.
              in addition", "ercc6.
              in addition to", "addition to rna", "to rna pol", "ii ercc6", "ercc6 and the", "and the ercc8", "the ercc8 complex", "complex the", "the transcription elongation", "transcription elongation factor", "elongation factor tfiih", "tfiih which", "which is also", "is also involved", "also involved in", "involved in global", "in global genome", "global genome nucleotide", "genome nucleotide excision", "repair gg", "is recruited to", "recruited to sites", "to sites of", "sites of tc", "of tc ner.", "tc ner. the", "ner. the tc", "the tc ner", "tc ner pre", "ner pre incision", "pre incision complex", "incision complex also", "complex also includes", "also includes xpa", "xpa xab2", "complex tcea1", "tcea1 tfiis", "hmgn1 uvssa", "uvssa in complex", "in complex with", "complex with usp7", "usp7 and", "ep300 p300", "p300 . xpa", ". xpa probably", "xpa probably contributes", "probably contributes to", "contributes to the", "to the assembly", "the assembly and", "assembly and stability", "and stability of", "stability of the", "of the pre", "the pre incision", "complex similar", "similar to its", "to its role", "its role in", "role in gg", "in gg ner.", "gg ner. the", "ner. the xab2", "the xab2 complex", "xab2 complex is", "complex is involved", "is involved in", "involved in pre", "in pre mrna", "pre mrna splicing", "mrna splicing and", "splicing and may", "and may modulate", "may modulate the", "modulate the structure", "the structure of", "structure of the", "of the nascent", "the nascent mrna", "nascent mrna hybrid", "mrna hybrid with", "hybrid with template", "with template dna", "template dna through", "dna through its", "through its rna", "its rna dna", "rna dna helicase", "dna helicase activity", "activity allowing", "allowing proper processing", "proper processing of", "processing of dna", "of dna damage.", "dna damage. tcea1", "damage. tcea1 may", "tcea1 may be", "may be involved", "be involved in", "involved in rna", "in rna pol", "pol ii backtracking", "backtracking which", "which allows repair", "allows repair proteins", "repair proteins to", "proteins to gain", "to gain access", "gain access to", "access to the", "to the damage", "the damage site.", "damage site. it", "site. it also", "it also facilitates", "also facilitates trimming", "facilitates trimming of", "trimming of the", "of the 3'", "the 3' end", "3' end of", "end of protruding", "of protruding nascent", "protruding nascent mrna", "nascent mrna from", "mrna from the", "from the stalled", "the stalled rna", "ii enabling", "enabling recovery of", "recovery of rna", "of rna synthesis", "rna synthesis after", "synthesis after repair.

              deubiquitinating", "after repair.

              deubiquitinating activity", "repair.

              deubiquitinating activity of", "activity of the", "of the uvssa:usp7", "the uvssa:usp7 complex", "uvssa:usp7 complex is", "complex is needed", "is needed for", "needed for ercc6", "for ercc6 stability", "ercc6 stability at", "stability at repair", "at repair sites.", "repair sites. non", "sites. non histone", "non histone nucleosomal", "histone nucleosomal binding", "nucleosomal binding protein", "binding protein hmgn1", "protein hmgn1 and", "hmgn1 and histone", "and histone acetyltransferase", "histone acetyltransferase p300", "p300 ep300", "ep300 remodel", "remodel the chromatin", "the chromatin around", "chromatin around the", "around the damaged", "the damaged site", "site thus", "thus facilitating repair.

              dual", "facilitating repair.

              dual incision", "repair.

              dual incision of", "incision of the", "of the lesion", "the lesion containing", "lesion containing oligonucleotide", "containing oligonucleotide from", "oligonucleotide from the", "from the affected", "the affected dna", "affected dna strand", "dna strand is", "strand is performed", "is performed by", "performed by two", "by two dna", "two dna endonucleases", "endonucleases the", "ercc1:ercc4 ercc1:xpf", "ercc1:xpf complex", "complex and ercc5", "ercc5 xpg", "which also participate", "also participate in", "participate in gg", "gg ner. dna", "ner. dna polymerases", "dna polymerases delta", "delta epsilon", "epsilon or kappa", "or kappa fill", "kappa fill in", "fill in the", "in the single", "the single stranded", "single stranded gap", "stranded gap after", "gap after dual", "after dual incision", "dual incision and", "incision and the", "and the remaining", "the remaining single", "remaining single strand", "single strand nick", "strand nick is", "nick is sealed", "is sealed by", "sealed by dna", "by dna ligases", "dna ligases lig1", "ligases lig1 or", "lig1 or lig3", "lig3 the", "the latter in", "latter in complex", "complex with xrcc1", "similar to gg", "to gg ner.", "gg ner. after", "ner. after the", "after the repair", "the repair of", "repair of dna", "of dna damage", "dna damage is", "damage is complete", "complete rna", "pol ii resumes", "ii resumes rna", "resumes rna synthesis.
              for", "rna synthesis.
              for past", "synthesis.
              for past and", "past and recent", "and recent reviews", "reviews see", "see mellon et", "mellon et al.", "et al. 1987", "1987 svejstrup", "2002 hanawalt", "hanawalt and spivak", "and spivak 2008", "2008 vermeulen", "vermeulen and fousteri", "and fousteri 2013", "fousteri 2013 and", "2013 and marteijn", "and marteijn et", "marteijn et al.", "et al. 2014.", "dna damage in transcribed", "damage in transcribed strands", "in transcribed strands of", "transcribed strands of active", "strands of active genes", "of active genes is", "active genes is repaired", "genes is repaired through", "is repaired through a", "repaired through a specialized", "through a specialized nucleotide", "a specialized nucleotide excision", "specialized nucleotide excision repair", "excision repair ner", "ner pathway known", "pathway known as transcription", "known as transcription coupled", "as transcription coupled nucleotide", "tc ner . tc", "ner . tc ner", ". tc ner impairment", "tc ner impairment is", "ner impairment is the", "impairment is the underlying", "is the underlying cause", "the underlying cause of", "underlying cause of a", "cause of a severe", "of a severe hereditary", "a severe hereditary disorder", "severe hereditary disorder cockayne", "hereditary disorder cockayne syndrome", "cockayne syndrome an", "syndrome an autosomal", "an autosomal recessive disease", "autosomal recessive disease characterized", "recessive disease characterized by", "disease characterized by hypersensitivity", "characterized by hypersensitivity to", "by hypersensitivity to uv", "hypersensitivity to uv light.
              tc", "to uv light.
              tc ner", "uv light.
              tc ner is", "light.
              tc ner is triggered", "ner is triggered by", "is triggered by helix", "triggered by helix distorting", "by helix distorting lesions", "helix distorting lesions that", "distorting lesions that block", "lesions that block the", "that block the progression", "block the progression of", "the progression of elongating", "progression of elongating rna", "of elongating rna polymerase", "elongating rna polymerase ii", "polymerase ii rna", "ii rna pol", "rna pol ii .", "pol ii . stalled", "ii . stalled rna", ". stalled rna pol", "stalled rna pol ii", "rna pol ii complex", "pol ii complex triggers", "ii complex triggers the", "complex triggers the recruitment", "triggers the recruitment of", "the recruitment of ercc6.", "recruitment of ercc6. ercc6", "ercc6. ercc6 commonly", "ercc6 commonly known", "commonly known as csb", "as csb cockayne", "csb cockayne syndrome", "cockayne syndrome protein b", "protein b recruits", "b recruits ercc8", "recruits ercc8 commonly", "ercc8 commonly known", "commonly known as csa", "as csa cockayne", "csa cockayne syndrome", "cockayne syndrome protein a", "syndrome protein a .", "protein a . ercc8", "a . ercc8 has", ". ercc8 has 7", "ercc8 has 7 wd", "has 7 wd repeat", "7 wd repeat motifs", "wd repeat motifs and", "repeat motifs and is", "motifs and is part", "and is part of", "is part of the", "part of the ubiquitin", "of the ubiquitin ligase", "the ubiquitin ligase complex", "ubiquitin ligase complex that", "ligase complex that also", "complex that also includes", "that also includes ddb1", "includes ddb1 cul4a", "ddb1 cul4a or", "cul4a or cul4b and", "or cul4b and rbx1.", "cul4b and rbx1. the", "and rbx1. the ercc8", "rbx1. the ercc8 ubiquitin", "the ercc8 ubiquitin ligase", "ercc8 ubiquitin ligase complex", "ubiquitin ligase complex is", "ligase complex is one", "complex is one of", "is one of the", "one of the key", "of the key regulators", "the key regulators of", "key regulators of tc", "regulators of tc ner", "of tc ner that", "tc ner that probably", "ner that probably exerts", "that probably exerts its", "probably exerts its role", "exerts its role by", "its role by ubiquitinating", "role by ubiquitinating one", "by ubiquitinating one or", "ubiquitinating one or more", "one or more factors", "or more factors involved", "more factors involved in", "factors involved in this", "involved in this repair", "in this repair process", "repair process including", "process including the", "including the rna pol", "the rna pol ii", "pol ii complex and", "ii complex and ercc6.
              in", "complex and ercc6.
              in addition", "and ercc6.
              in addition to", "ercc6.
              in addition to rna", "addition to rna pol", "to rna pol ii", "pol ii ercc6", "ii ercc6 and", "ercc6 and the ercc8", "and the ercc8 complex", "ercc8 complex the", "complex the transcription", "the transcription elongation factor", "transcription elongation factor tfiih", "factor tfiih which", "tfiih which is", "which is also involved", "is also involved in", "also involved in global", "involved in global genome", "in global genome nucleotide", "global genome nucleotide excision", "genome nucleotide excision repair", "excision repair gg", "repair gg ner", "is recruited to sites", "recruited to sites of", "to sites of tc", "sites of tc ner.", "of tc ner. the", "tc ner. the tc", "ner. the tc ner", "the tc ner pre", "tc ner pre incision", "ner pre incision complex", "pre incision complex also", "incision complex also includes", "complex also includes xpa", "includes xpa xab2", "xpa xab2 complex", "xab2 complex tcea1", "tfiis hmgn1", "hmgn1 uvssa in", "uvssa in complex with", "in complex with usp7", "with usp7 and", "usp7 and ep300", "and ep300 p300", "ep300 p300 .", "p300 . xpa probably", ". xpa probably contributes", "xpa probably contributes to", "probably contributes to the", "contributes to the assembly", "to the assembly and", "the assembly and stability", "assembly and stability of", "and stability of the", "stability of the pre", "of the pre incision", "the pre incision complex", "incision complex similar", "complex similar to", "similar to its role", "to its role in", "its role in gg", "role in gg ner.", "in gg ner. the", "gg ner. the xab2", "ner. the xab2 complex", "the xab2 complex is", "xab2 complex is involved", "complex is involved in", "is involved in pre", "involved in pre mrna", "in pre mrna splicing", "pre mrna splicing and", "mrna splicing and may", "splicing and may modulate", "and may modulate the", "may modulate the structure", "modulate the structure of", "the structure of the", "structure of the nascent", "of the nascent mrna", "the nascent mrna hybrid", "nascent mrna hybrid with", "mrna hybrid with template", "hybrid with template dna", "with template dna through", "template dna through its", "dna through its rna", "through its rna dna", "its rna dna helicase", "rna dna helicase activity", "helicase activity allowing", "activity allowing proper", "allowing proper processing of", "proper processing of dna", "processing of dna damage.", "of dna damage. tcea1", "dna damage. tcea1 may", "damage. tcea1 may be", "tcea1 may be involved", "may be involved in", "be involved in rna", "involved in rna pol", "in rna pol ii", "rna pol ii backtracking", "ii backtracking which", "backtracking which allows", "which allows repair proteins", "allows repair proteins to", "repair proteins to gain", "proteins to gain access", "to gain access to", "gain access to the", "access to the damage", "to the damage site.", "the damage site. it", "damage site. it also", "site. it also facilitates", "it also facilitates trimming", "also facilitates trimming of", "facilitates trimming of the", "trimming of the 3'", "of the 3' end", "the 3' end of", "3' end of protruding", "end of protruding nascent", "of protruding nascent mrna", "protruding nascent mrna from", "nascent mrna from the", "mrna from the stalled", "from the stalled rna", "the stalled rna pol", "pol ii enabling", "ii enabling recovery", "enabling recovery of rna", "recovery of rna synthesis", "of rna synthesis after", "rna synthesis after repair.

              deubiquitinating", "synthesis after repair.

              deubiquitinating activity", "after repair.

              deubiquitinating activity of", "repair.

              deubiquitinating activity of the", "activity of the uvssa:usp7", "of the uvssa:usp7 complex", "the uvssa:usp7 complex is", "uvssa:usp7 complex is needed", "complex is needed for", "is needed for ercc6", "needed for ercc6 stability", "for ercc6 stability at", "ercc6 stability at repair", "stability at repair sites.", "at repair sites. non", "repair sites. non histone", "sites. non histone nucleosomal", "non histone nucleosomal binding", "histone nucleosomal binding protein", "nucleosomal binding protein hmgn1", "binding protein hmgn1 and", "protein hmgn1 and histone", "hmgn1 and histone acetyltransferase", "and histone acetyltransferase p300", "acetyltransferase p300 ep300", "ep300 remodel the", "remodel the chromatin around", "the chromatin around the", "chromatin around the damaged", "around the damaged site", "damaged site thus", "site thus facilitating", "thus facilitating repair.

              dual incision", "facilitating repair.

              dual incision of", "repair.

              dual incision of the", "incision of the lesion", "of the lesion containing", "the lesion containing oligonucleotide", "lesion containing oligonucleotide from", "containing oligonucleotide from the", "oligonucleotide from the affected", "from the affected dna", "the affected dna strand", "affected dna strand is", "dna strand is performed", "strand is performed by", "is performed by two", "performed by two dna", "by two dna endonucleases", "dna endonucleases the", "endonucleases the ercc1:ercc4", "the ercc1:ercc4 ercc1:xpf", "ercc1:xpf complex and", "and ercc5 xpg", "xpg which", "which also participate in", "also participate in gg", "participate in gg ner.", "in gg ner. dna", "gg ner. dna polymerases", "ner. dna polymerases delta", "polymerases delta epsilon", "delta epsilon or", "epsilon or kappa fill", "or kappa fill in", "kappa fill in the", "fill in the single", "in the single stranded", "the single stranded gap", "single stranded gap after", "stranded gap after dual", "gap after dual incision", "after dual incision and", "dual incision and the", "incision and the remaining", "and the remaining single", "the remaining single strand", "remaining single strand nick", "single strand nick is", "strand nick is sealed", "nick is sealed by", "is sealed by dna", "sealed by dna ligases", "by dna ligases lig1", "dna ligases lig1 or", "ligases lig1 or lig3", "or lig3 the", "lig3 the latter", "the latter in complex", "latter in complex with", "in complex with xrcc1", "xrcc1 similar", "similar to gg ner.", "to gg ner. after", "gg ner. after the", "ner. after the repair", "after the repair of", "the repair of dna", "repair of dna damage", "of dna damage is", "dna damage is complete", "is complete rna", "complete rna pol", "rna pol ii resumes", "pol ii resumes rna", "ii resumes rna synthesis.
              for", "resumes rna synthesis.
              for past", "rna synthesis.
              for past and", "synthesis.
              for past and recent", "past and recent reviews", "recent reviews see", "reviews see mellon", "see mellon et al.", "mellon et al. 1987", "al. 1987 svejstrup", "1987 svejstrup 2002", "svejstrup 2002 hanawalt", "2002 hanawalt and", "hanawalt and spivak 2008", "spivak 2008 vermeulen", "2008 vermeulen and", "vermeulen and fousteri 2013", "and fousteri 2013 and", "fousteri 2013 and marteijn", "2013 and marteijn et", "and marteijn et al.", "marteijn et al. 2014.", "dna damage in transcribed strands", "damage in transcribed strands of", "in transcribed strands of active", "transcribed strands of active genes", "strands of active genes is", "of active genes is repaired", "active genes is repaired through", "genes is repaired through a", "is repaired through a specialized", "repaired through a specialized nucleotide", "through a specialized nucleotide excision", "a specialized nucleotide excision repair", "nucleotide excision repair ner", "repair ner pathway", "ner pathway known as", "pathway known as transcription coupled", "known as transcription coupled nucleotide", "as transcription coupled nucleotide excision", "repair tc ner .", "tc ner . tc ner", "ner . tc ner impairment", ". tc ner impairment is", "tc ner impairment is the", "ner impairment is the underlying", "impairment is the underlying cause", "is the underlying cause of", "the underlying cause of a", "underlying cause of a severe", "cause of a severe hereditary", "of a severe hereditary disorder", "a severe hereditary disorder cockayne", "severe hereditary disorder cockayne syndrome", "disorder cockayne syndrome an", "cockayne syndrome an autosomal", "syndrome an autosomal recessive", "an autosomal recessive disease characterized", "autosomal recessive disease characterized by", "recessive disease characterized by hypersensitivity", "disease characterized by hypersensitivity to", "characterized by hypersensitivity to uv", "by hypersensitivity to uv light.
              tc", "hypersensitivity to uv light.
              tc ner", "to uv light.
              tc ner is", "uv light.
              tc ner is triggered", "light.
              tc ner is triggered by", "ner is triggered by helix", "is triggered by helix distorting", "triggered by helix distorting lesions", "by helix distorting lesions that", "helix distorting lesions that block", "distorting lesions that block the", "lesions that block the progression", "that block the progression of", "block the progression of elongating", "the progression of elongating rna", "progression of elongating rna polymerase", "of elongating rna polymerase ii", "rna polymerase ii rna", "polymerase ii rna pol", "ii rna pol ii", "rna pol ii . stalled", "pol ii . stalled rna", "ii . stalled rna pol", ". stalled rna pol ii", "stalled rna pol ii complex", "rna pol ii complex triggers", "pol ii complex triggers the", "ii complex triggers the recruitment", "complex triggers the recruitment of", "triggers the recruitment of ercc6.", "the recruitment of ercc6. ercc6", "of ercc6. ercc6 commonly", "ercc6. ercc6 commonly known", "ercc6 commonly known as", "known as csb cockayne", "as csb cockayne syndrome", "csb cockayne syndrome protein", "syndrome protein b recruits", "protein b recruits ercc8", "recruits ercc8 commonly known", "ercc8 commonly known as", "known as csa cockayne", "as csa cockayne syndrome", "csa cockayne syndrome protein", "cockayne syndrome protein a .", "syndrome protein a . ercc8", "protein a . ercc8 has", "a . ercc8 has 7", ". ercc8 has 7 wd", "ercc8 has 7 wd repeat", "has 7 wd repeat motifs", "7 wd repeat motifs and", "wd repeat motifs and is", "repeat motifs and is part", "motifs and is part of", "and is part of the", "is part of the ubiquitin", "part of the ubiquitin ligase", "of the ubiquitin ligase complex", "the ubiquitin ligase complex that", "ubiquitin ligase complex that also", "ligase complex that also includes", "complex that also includes ddb1", "also includes ddb1 cul4a", "includes ddb1 cul4a or", "ddb1 cul4a or cul4b", "cul4a or cul4b and rbx1.", "or cul4b and rbx1. the", "cul4b and rbx1. the ercc8", "and rbx1. the ercc8 ubiquitin", "rbx1. the ercc8 ubiquitin ligase", "the ercc8 ubiquitin ligase complex", "ercc8 ubiquitin ligase complex is", "ubiquitin ligase complex is one", "ligase complex is one of", "complex is one of the", "is one of the key", "one of the key regulators", "of the key regulators of", "the key regulators of tc", "key regulators of tc ner", "regulators of tc ner that", "of tc ner that probably", "tc ner that probably exerts", "ner that probably exerts its", "that probably exerts its role", "probably exerts its role by", "exerts its role by ubiquitinating", "its role by ubiquitinating one", "role by ubiquitinating one or", "by ubiquitinating one or more", "ubiquitinating one or more factors", "one or more factors involved", "or more factors involved in", "more factors involved in this", "factors involved in this repair", "involved in this repair process", "this repair process including", "repair process including the", "process including the rna", "including the rna pol ii", "the rna pol ii complex", "rna pol ii complex and", "pol ii complex and ercc6.
              in", "ii complex and ercc6.
              in addition", "complex and ercc6.
              in addition to", "and ercc6.
              in addition to rna", "ercc6.
              in addition to rna pol", "addition to rna pol ii", "rna pol ii ercc6", "pol ii ercc6 and", "ii ercc6 and the", "ercc6 and the ercc8 complex", "the ercc8 complex the", "ercc8 complex the transcription", "complex the transcription elongation", "the transcription elongation factor tfiih", "elongation factor tfiih which", "factor tfiih which is", "tfiih which is also", "which is also involved in", "is also involved in global", "also involved in global genome", "involved in global genome nucleotide", "in global genome nucleotide excision", "global genome nucleotide excision repair", "nucleotide excision repair gg", "excision repair gg ner", "gg ner is", "ner is recruited", "is recruited to sites of", "recruited to sites of tc", "to sites of tc ner.", "sites of tc ner. the", "of tc ner. the tc", "tc ner. the tc ner", "ner. the tc ner pre", "the tc ner pre incision", "tc ner pre incision complex", "ner pre incision complex also", "pre incision complex also includes", "incision complex also includes xpa", "also includes xpa xab2", "includes xpa xab2 complex", "complex tcea1 tfiis", "hmgn1 uvssa in complex", "uvssa in complex with usp7", "complex with usp7 and", "with usp7 and ep300", "and ep300 p300 .", "ep300 p300 . xpa", "p300 . xpa probably contributes", ". xpa probably contributes to", "xpa probably contributes to the", "probably contributes to the assembly", "contributes to the assembly and", "to the assembly and stability", "the assembly and stability of", "assembly and stability of the", "and stability of the pre", "stability of the pre incision", "of the pre incision complex", "pre incision complex similar", "incision complex similar to", "complex similar to its", "similar to its role in", "to its role in gg", "its role in gg ner.", "role in gg ner. the", "in gg ner. the xab2", "gg ner. the xab2 complex", "ner. the xab2 complex is", "the xab2 complex is involved", "xab2 complex is involved in", "complex is involved in pre", "is involved in pre mrna", "involved in pre mrna splicing", "in pre mrna splicing and", "pre mrna splicing and may", "mrna splicing and may modulate", "splicing and may modulate the", "and may modulate the structure", "may modulate the structure of", "modulate the structure of the", "the structure of the nascent", "structure of the nascent mrna", "of the nascent mrna hybrid", "the nascent mrna hybrid with", "nascent mrna hybrid with template", "mrna hybrid with template dna", "hybrid with template dna through", "with template dna through its", "template dna through its rna", "dna through its rna dna", "through its rna dna helicase", "its rna dna helicase activity", "dna helicase activity allowing", "helicase activity allowing proper", "activity allowing proper processing", "allowing proper processing of dna", "proper processing of dna damage.", "processing of dna damage. tcea1", "of dna damage. tcea1 may", "dna damage. tcea1 may be", "damage. tcea1 may be involved", "tcea1 may be involved in", "may be involved in rna", "be involved in rna pol", "involved in rna pol ii", "in rna pol ii backtracking", "pol ii backtracking which", "ii backtracking which allows", "backtracking which allows repair", "which allows repair proteins to", "allows repair proteins to gain", "repair proteins to gain access", "proteins to gain access to", "to gain access to the", "gain access to the damage", "access to the damage site.", "to the damage site. it", "the damage site. it also", "damage site. it also facilitates", "site. it also facilitates trimming", "it also facilitates trimming of", "also facilitates trimming of the", "facilitates trimming of the 3'", "trimming of the 3' end", "of the 3' end of", "the 3' end of protruding", "3' end of protruding nascent", "end of protruding nascent mrna", "of protruding nascent mrna from", "protruding nascent mrna from the", "nascent mrna from the stalled", "mrna from the stalled rna", "from the stalled rna pol", "the stalled rna pol ii", "rna pol ii enabling", "pol ii enabling recovery", "ii enabling recovery of", "enabling recovery of rna synthesis", "recovery of rna synthesis after", "of rna synthesis after repair.

              deubiquitinating", "rna synthesis after repair.

              deubiquitinating activity", "synthesis after repair.

              deubiquitinating activity of", "after repair.

              deubiquitinating activity of the", "repair.

              deubiquitinating activity of the uvssa:usp7", "activity of the uvssa:usp7 complex", "of the uvssa:usp7 complex is", "the uvssa:usp7 complex is needed", "uvssa:usp7 complex is needed for", "complex is needed for ercc6", "is needed for ercc6 stability", "needed for ercc6 stability at", "for ercc6 stability at repair", "ercc6 stability at repair sites.", "stability at repair sites. non", "at repair sites. non histone", "repair sites. non histone nucleosomal", "sites. non histone nucleosomal binding", "non histone nucleosomal binding protein", "histone nucleosomal binding protein hmgn1", "nucleosomal binding protein hmgn1 and", "binding protein hmgn1 and histone", "protein hmgn1 and histone acetyltransferase", "hmgn1 and histone acetyltransferase p300", "histone acetyltransferase p300 ep300", "p300 ep300 remodel", "ep300 remodel the chromatin", "remodel the chromatin around the", "the chromatin around the damaged", "chromatin around the damaged site", "the damaged site thus", "damaged site thus facilitating", "site thus facilitating repair.

              dual", "thus facilitating repair.

              dual incision of", "facilitating repair.

              dual incision of the", "repair.

              dual incision of the lesion", "incision of the lesion containing", "of the lesion containing oligonucleotide", "the lesion containing oligonucleotide from", "lesion containing oligonucleotide from the", "containing oligonucleotide from the affected", "oligonucleotide from the affected dna", "from the affected dna strand", "the affected dna strand is", "affected dna strand is performed", "dna strand is performed by", "strand is performed by two", "is performed by two dna", "performed by two dna endonucleases", "two dna endonucleases the", "dna endonucleases the ercc1:ercc4", "ercc1:ercc4 ercc1:xpf complex", "ercc1:xpf complex and ercc5", "complex and ercc5 xpg", "xpg which also", "which also participate in gg", "also participate in gg ner.", "participate in gg ner. dna", "in gg ner. dna polymerases", "gg ner. dna polymerases delta", "dna polymerases delta epsilon", "polymerases delta epsilon or", "delta epsilon or kappa", "epsilon or kappa fill in", "or kappa fill in the", "kappa fill in the single", "fill in the single stranded", "in the single stranded gap", "the single stranded gap after", "single stranded gap after dual", "stranded gap after dual incision", "gap after dual incision and", "after dual incision and the", "dual incision and the remaining", "incision and the remaining single", "and the remaining single strand", "the remaining single strand nick", "remaining single strand nick is", "single strand nick is sealed", "strand nick is sealed by", "nick is sealed by dna", "is sealed by dna ligases", "sealed by dna ligases lig1", "by dna ligases lig1 or", "dna ligases lig1 or lig3", "lig1 or lig3 the", "or lig3 the latter", "lig3 the latter in", "the latter in complex with", "latter in complex with xrcc1", "with xrcc1 similar", "xrcc1 similar to", "similar to gg ner. after", "to gg ner. after the", "gg ner. after the repair", "ner. after the repair of", "after the repair of dna", "the repair of dna damage", "repair of dna damage is", "of dna damage is complete", "damage is complete rna", "is complete rna pol", "complete rna pol ii", "rna pol ii resumes rna", "pol ii resumes rna synthesis.
              for", "ii resumes rna synthesis.
              for past", "resumes rna synthesis.
              for past and", "rna synthesis.
              for past and recent", "synthesis.
              for past and recent reviews", "and recent reviews see", "recent reviews see mellon", "reviews see mellon et", "see mellon et al. 1987", "et al. 1987 svejstrup", "al. 1987 svejstrup 2002", "svejstrup 2002 hanawalt and", "2002 hanawalt and spivak", "and spivak 2008 vermeulen", "spivak 2008 vermeulen and", "2008 vermeulen and fousteri", "vermeulen and fousteri 2013 and", "and fousteri 2013 and marteijn", "fousteri 2013 and marteijn et", "2013 and marteijn et al.", "and marteijn et al. 2014." ] }, { "record_id": "GLY_000594_1_1085", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6782135", "r hsa", "hsa 6782135", "r hsa 6782135" ] }, { "record_id": "GLY_000594_1_1085", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dual incision", "incision in", "in tc", "tc ner", "dual incision in", "incision in tc", "in tc ner", "dual incision in tc", "incision in tc ner", "dual incision in tc 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"ner similar", "similar to global genome", "to global genome nucleotide", "global genome nucleotide excision", "genome nucleotide excision repair", "excision repair gg", "repair gg ner", "ner the", "the oligonucleotide that contains", "oligonucleotide that contains the", "that contains the lesion", "contains the lesion is", "the lesion is excised", "lesion is excised from", "is excised from the", "excised from the open", "from the open bubble", "the open bubble structure", "open bubble structure via", "bubble structure via dual", "structure via dual incision", "via dual incision of", "dual incision of the", "incision of the affected", "of the affected dna", "the affected dna strand.", "affected dna strand. 5'", "dna strand. 5' incision", "strand. 5' incision by", "5' incision by the", "incision by the ercc1:ercc4", "the ercc1:ercc4 ercc1:xpf", "ercc1:xpf endonuclease precedes", "endonuclease precedes 3' incision", "precedes 3' incision by", "3' incision by ercc5", "by ercc5 xpg", "xpg 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process are largely", "process are largely unknown", "are largely unknown in", "largely unknown in mammals", "in mammals it", "mammals it may", "it may involve ercc6/ercc8", "may involve ercc6/ercc8 mediated", "involve ercc6/ercc8 mediated chromatin", "ercc6/ercc8 mediated chromatin remodelling/ubiquitination", "mediated chromatin remodelling/ubiquitination events", "remodelling/ubiquitination events the", "events the dna", "the dna helicase activity", "dna helicase activity of", "helicase activity of the", "activity of the tfiih", "of the tfiih complex", "the tfiih complex and", "tfiih complex and tcea1", "and tcea1 tfiis", "tfiis stimulated cleavage", "stimulated cleavage of the", "cleavage of the 3'", "of the 3' protruding", "the 3' protruding end", "3' protruding end of", "protruding end of nascent", "end of nascent mrna", "of nascent mrna by", "nascent mrna by rna", "mrna by rna pol", "by rna pol ii", "pol ii donahue", "ii donahue et", "donahue et al. 1994", "al. 1994 lee", "1994 lee et", "lee et al. 2002", "al. 2002 sarker", "2002 sarker et", "sarker et al. 2005", "al. 2005 vermeulen", "2005 vermeulen and", "vermeulen and fousteri 2013", "fousteri 2013 hanawalt", "2013 hanawalt and", "hanawalt and spivak 2008", "spivak 2008 staresincic", "2008 staresincic et", "staresincic et al. 2009", "al. 2009 epshtein", "2009 epshtein et", "epshtein et al. 2014", "et al. 2014 .", "in transcription coupled nucleotide excision", "transcription coupled nucleotide excision repair", "nucleotide excision repair tc", "excision repair tc ner", "tc ner similar", "ner similar to", "similar to global genome nucleotide", "to global genome nucleotide excision", "global genome nucleotide excision repair", "nucleotide excision repair gg", "excision repair gg ner", "gg ner the", "ner the oligonucleotide", "the oligonucleotide that contains the", "oligonucleotide that contains the lesion", "that contains the lesion is", "contains the lesion is excised", "the lesion is excised from", 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process are largely", "this process are largely unknown", "process are largely unknown in", "are largely unknown in mammals", "unknown in mammals it", "in mammals it may", "mammals it may involve", "it may involve ercc6/ercc8 mediated", "may involve ercc6/ercc8 mediated chromatin", "involve ercc6/ercc8 mediated chromatin remodelling/ubiquitination", "ercc6/ercc8 mediated chromatin remodelling/ubiquitination events", "chromatin remodelling/ubiquitination events the", "remodelling/ubiquitination events the dna", "events the dna helicase", "the dna helicase activity of", "dna helicase activity of the", "helicase activity of the tfiih", "activity of the tfiih complex", "of the tfiih complex and", "the tfiih complex and tcea1", "complex and tcea1 tfiis", "tcea1 tfiis stimulated", "tfiis stimulated cleavage of", "stimulated cleavage of the 3'", "cleavage of the 3' protruding", "of the 3' protruding end", "the 3' protruding end of", "3' protruding end of nascent", "protruding end of nascent 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hsa", "hsa 6788467", "r hsa 6788467" ] }, { "record_id": "GLY_000594_1_1087", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "il 6", "6 type", "type cytokine", "cytokine receptor", "receptor ligand", "ligand interactions", "il 6 type", "6 type cytokine", "type cytokine receptor", "cytokine receptor ligand", "receptor ligand interactions", "il 6 type cytokine", "6 type cytokine receptor", "type cytokine receptor ligand", "cytokine receptor ligand interactions", "il 6 type cytokine receptor", "6 type cytokine receptor ligand", "type cytokine receptor ligand interactions", "the members", "members involved", "involved in", "cytokine signalling", "signalling are", "are the", "the il", "il 11", "leukaemia inhibitory", "inhibitory factor", "oncostatin m", "ciliary neurotrophic", "neurotrophic factor", "cardiotrophin 1", "and cardiotrophin", "cardiotrophin like", "like cytokine", "cytokine factor", "factor 1", "clcf1 .", ". receptors", "receptors involved", 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jaks", "with jaks and", "jaks and become", "and become tyrosine", "become tyrosine phosphorylated", "tyrosine phosphorylated in", "phosphorylated in response", "in response to", "response to cytokine", "to cytokine stimulation", "stimulation heinrich", "heinrich et al.", "et al. 1998", "1998 2003", "2003 . il27", ". il27 and", "il27 and il35", "and il35 belongs", "il35 belongs to", "belongs to il12", "to il12 cytokine", "il12 cytokine family", "cytokine family but", "family but they", "but they share", "they share gp130", "share gp130 as", "gp130 as a", "as a component", "a component of", "component of signalling", "of signalling receptor", "receptor along", "along with il", "with il 6", "lif osm", "osm cntf", "cntf ctf1", "ctf1 and clcf1.", "the members involved in", "involved in interleukin", "interleukin 6 type", "6 type cytokine signalling", "type cytokine signalling are", "cytokine signalling are the", "signalling are the il", "are the il 6", "il 6 il", "6 il 11", "il 11 lif", "lif leukaemia inhibitory", "factor osm", "osm oncostatin m", "m ciliary", "neurotrophic factor cntf", "cntf cardiotrophin", "cardiotrophin 1 ctf1", "ctf1 and cardiotrophin", "and cardiotrophin like cytokine", "cardiotrophin like cytokine factor", "like cytokine factor 1", "factor 1 clcf1", "1 clcf1 .", "clcf1 . receptors involved", ". receptors involved in", "receptors involved in recognition", "involved in recognition of", "in recognition of the", "recognition of the il", "of the il 6", "the il 6 type", "il 6 type cytokines", "6 type cytokines can", "type cytokines can be", "cytokines can be subdivided", "can be subdivided in", "be subdivided in the", "subdivided in the non", "in the non signalling", "the non signalling alpha", "non signalling alpha receptors", "alpha receptors il6r", "il6r il 11r", "il 11r and", "11r and cntfr", "and cntfr and", "cntfr and the", "and the signal transducing", "the signal transducing receptors", "transducing receptors gp130", "lifr and osmr", "and osmr . the", "osmr . the latter", ". the latter associate", "the latter associate with", "latter associate with jaks", "associate with jaks and", "with jaks and become", "jaks and become tyrosine", "and become tyrosine phosphorylated", "become tyrosine phosphorylated in", "tyrosine phosphorylated in response", "phosphorylated in response to", "in response to cytokine", "response to cytokine stimulation", "cytokine stimulation heinrich", "stimulation heinrich et", "heinrich et al. 1998", "al. 1998 2003", "1998 2003 .", "2003 . il27 and", ". il27 and il35", "il27 and il35 belongs", "and il35 belongs to", "il35 belongs to il12", "belongs to il12 cytokine", "to il12 cytokine family", "il12 cytokine family but", "cytokine family but they", "family but they share", "but they share gp130", "they share gp130 as", "share gp130 as a", "gp130 as a component", "as a component of", "a component of signalling", "component of signalling receptor", "signalling receptor along", "receptor along with", "along with il 6", "cntf ctf1 and", "members involved in interleukin", "in interleukin 6", "interleukin 6 type cytokine", "6 type cytokine signalling are", "type cytokine signalling are the", "cytokine signalling are the il", "signalling are the il 6", "the il 6 il", "il 6 il 11", "11 lif leukaemia", "lif leukaemia inhibitory factor", "inhibitory factor osm", "oncostatin m ciliary", "m ciliary neurotrophic", "ciliary neurotrophic factor cntf", "cntf cardiotrophin 1", "1 ctf1 and", "ctf1 and cardiotrophin like", "and cardiotrophin like cytokine factor", "cardiotrophin like cytokine factor 1", "cytokine factor 1 clcf1", "factor 1 clcf1 .", "1 clcf1 . receptors", "clcf1 . receptors involved in", ". receptors involved in recognition", "receptors involved in recognition of", "involved in recognition of the", "in recognition of the il", "recognition of the il 6", "of the il 6 type", "the il 6 type cytokines", "il 6 type cytokines can", "6 type cytokines can be", "type cytokines can be subdivided", "cytokines can be subdivided in", "can be subdivided in the", "be subdivided in the non", "subdivided in the non signalling", "in the non signalling alpha", "the non signalling alpha receptors", "signalling alpha receptors il6r", "receptors il6r il", "il 11r and cntfr", "and cntfr and the", "cntfr and the signal", "and the signal transducing receptors", "signal transducing receptors gp130", "receptors gp130 lifr", "gp130 lifr and", "lifr and osmr .", "and osmr . the latter", "osmr . the latter associate", ". the latter associate with", "the latter associate with jaks", "latter associate with jaks and", "associate with jaks and become", "with jaks and become tyrosine", "jaks and become tyrosine phosphorylated", "and become tyrosine phosphorylated in", "become tyrosine phosphorylated in response", "tyrosine phosphorylated in response to", "phosphorylated in response to cytokine", "in response to cytokine stimulation", "to cytokine stimulation heinrich", "cytokine stimulation heinrich et", "stimulation heinrich et al.", "et al. 1998 2003", "al. 1998 2003 .", "1998 2003 . il27", "2003 . il27 and il35", ". il27 and il35 belongs", "il27 and il35 belongs to", "and il35 belongs to il12", "il35 belongs to il12 cytokine", "belongs to il12 cytokine family", "to il12 cytokine family but", "il12 cytokine family but they", "cytokine family but they share", "family but they share gp130", "but they share gp130 as", "they share gp130 as a", "share gp130 as a component", "gp130 as a component of", "as a component of signalling", "a component of signalling receptor", "of signalling receptor along", "signalling receptor along with", "receptor along with il", "with il 6 il", "11 lif osm", "lif osm cntf", "osm cntf ctf1", "cntf ctf1 and clcf1." ] }, { "record_id": "GLY_000594_1_1088", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6802946", "r hsa", "hsa 6802946", "r hsa 6802946" ] }, { "record_id": "GLY_000594_1_1088", 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cell", "cell leukemia", "papillary thyroid", "thyroid and", "and ovarian", "ovarian carcinomas", "colorectal cancer", "cancer and", "and a", "a variety", "variety of", "of other", "other tumors", "davies et", "et al", "reviewed in", "in samatar", "samatar and", "and poulikakos", "2014 .", ". most", "most braf", "braf mutations", "mutations fall", "fall in", "in the", "the activation", "activation loop", "loop region", "region of", "of the", "the kinase", "kinase or", "or the", "the adjacent", "adjacent glycine", "glycine rich", "rich region.", "region. these", "these mutations", "mutations promote", "promote increased", "increased kinase", "activity either", "either by", "by mimicking", "mimicking the", "the effects", "effects of", "of activation", "loop phosphorylations", "phosphorylations or", "or by", "by promoting", "promoting the", "the active", "active conformation", "conformation of", "the enzyme", "wan et", "2004 .", ". roughly", "roughly 90%", "90% of", "of braf", "mutants are", "are represented", "represented by", "by the", "the single", "single missense", "missense mutation", "mutation braf", "braf v600e", ". other", "other highly", "highly active", "active kinase", "kinase mutants", "mutants of", "braf include", "include braf", "braf g469a", "g469a and", "and braf", "braf t599dup.", "t599dup. g469", "g469 is", "is in", "the glycine", "rich region", "kinase domain", "domain which", "which plays", "plays a", "a role", "role in", "in orienting", "orienting atp", "atp for", "for catalysis", "while t599", "t599 is", "is one", "one of", "the two", "two conserved", "conserved regulatory", "regulatory phosphorylation", "phosphorylation sites", "sites of", "activation loop.", "loop. each", "each of", "of these", "these mutants", "mutants has", "has highly", "highly enhanced", "enhanced basal", "basal kinase", "kinase activities", "phosphorylates mek", "mek and", "and erk", "erk in", "in vitro", "vitro and", "and in", "in vivo", "vivo and", "and is", "is 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"prevalence in hairy", "in hairy cell", "hairy cell leukemia", "leukemia melanoma", "melanoma papillary", "papillary thyroid and", "thyroid and ovarian", "and ovarian carcinomas", "carcinomas colorectal", "colorectal cancer and", "cancer and a", "and a variety", "a variety of", "variety of other", "of other tumors", "tumors davies", "davies et al", "al 2002", "2002 reviewed", "reviewed in samatar", "in samatar and", "samatar and poulikakos", "poulikakos 2014", "2014 . most", ". most braf", "most braf mutations", "braf mutations fall", "mutations fall in", "fall in the", "in the activation", "the activation loop", "activation loop region", "loop region of", "region of the", "of the kinase", "the kinase or", "kinase or the", "or the adjacent", "the adjacent glycine", "adjacent glycine rich", "glycine rich region.", "rich region. these", "region. these mutations", "these mutations promote", "mutations promote increased", "promote increased kinase", "increased kinase activity", "kinase activity either", "activity either by", "either by mimicking", "by mimicking the", "mimicking the effects", "the effects of", "effects of activation", "of activation loop", "activation loop phosphorylations", "loop phosphorylations or", "phosphorylations or by", "or by promoting", "by promoting the", "promoting the active", "the active conformation", "active conformation of", "conformation of the", "of the enzyme", "enzyme davies", "2002 wan", "wan et al", "al 2004", "2004 . roughly", ". roughly 90%", "roughly 90% of", "90% of braf", "of braf mutants", "braf mutants are", "mutants are represented", "are represented by", "represented by the", "by the single", "the single missense", "single missense mutation", "missense mutation braf", "mutation braf v600e", "v600e davies", "2004 . other", ". other highly", "other highly active", "highly active kinase", "active kinase mutants", "kinase mutants of", "mutants of braf", "of braf include", "braf include braf", "include braf g469a", "braf g469a and", "g469a and braf", "and braf t599dup.", "braf t599dup. g469", "t599dup. g469 is", "g469 is in", "is in the", "in the glycine", "the glycine rich", "glycine rich region", "rich region of", "the kinase domain", "kinase domain which", "domain which plays", "which plays a", "plays a role", "a role in", "role in orienting", "in orienting atp", "orienting atp for", "atp for catalysis", "catalysis while", "while t599 is", "t599 is one", "is one of", "one of the", "of the two", "the two conserved", "two conserved regulatory", "conserved regulatory phosphorylation", "regulatory phosphorylation sites", "phosphorylation sites of", "sites of the", "of the activation", "the activation loop.", "activation loop. each", "loop. each of", "each of these", "of these mutants", "these mutants has", "mutants has highly", "has highly enhanced", "highly enhanced basal", "enhanced basal kinase", "basal kinase activities", "activities phosphorylates", "phosphorylates mek and", "mek and erk", "and erk in", "erk in vitro", "in vitro and", "vitro and in", "and in vivo", "in vivo and", "vivo and is", "and is transforming", "is transforming when", "transforming when expressed", "when expressed in", "expressed in vivo", "vivo davies", "2004 eisenhardt", "eisenhardt et al", "al 2011", "2011 . further", ". further functional", "further functional characterization", "functional characterization shows", "characterization shows that", "shows that these", "that these highly", "these highly active", "highly active mutants", "active mutants are", "mutants are largely", "are largely resistant", "largely resistant to", "resistant to disruption", "to disruption of", "disruption of the", "of the braf", "the braf dimer", "braf dimer interface", "interface suggesting", "suggesting that they", "that they are", "they are able", "are able to", "able to act", "to act as", "act as monomers", "monomers roring", "roring et al", "al 2012", "2012 brummer", "brummer et al", "al 2006", "2006 freeman", "freeman et al", "al 2013", "2013 garnett", "garnett et al", "al 2005", "2005 . activating", ". activating braf", "activating braf mutations", "braf mutations occur", "mutations occur for", "occur for the", "for the most", "the most part", "most part independently", "part independently of", "independently of ras", "of ras activating", "ras activating mutations", "mutations and", "and ras activity", "ras activity levels", "activity levels are", "levels are generally", "are generally low", "generally low in", "low in braf", "in braf mutant", "braf mutant cells.", "mutant cells. moreover", "moreover the", "the kinase activity", "kinase activity of", "activity of these", "these mutants is", "mutants is only", "is only slightly", "only slightly elevated", "slightly elevated by", "elevated by coexpression", "by coexpression of", "coexpression of g12v", "of g12v kras", "kras and", "and biological activity", "biological activity of", "activity of the", "of the highly", "the highly active", "highly active braf", "active braf mutants", "braf mutants is", "mutants is independent", "is independent of", "independent of ras", "of ras binding", "binding brummer", "2006 wan", "2004 davies", "2002 garnett", "2005 . although", ". although braf", "although braf v600e", "braf v600e is", "v600e is inhibited", "is inhibited by", "inhibited by raf", "by raf inhibitors", "raf inhibitors such", "inhibitors such as", "such as vemurafenib", "vemurafenib resistance", "resistance frequently develops", "develops in", "in some cases", "some cases mediated", "cases mediated by", "mediated by the", "by the expression", "the expression of", "expression of a", "of a splice", "a splice variant", "splice variant that", "variant that lacks", "that lacks the", "lacks the ras", "the ras binding", "ras binding domain", "binding domain and", "domain and shows", "and shows elevated", "shows elevated dimerization", "elevated dimerization compared", "dimerization compared to", "compared to the", "to the full", "the full length", "full length v600e", "length v600e mutant", "mutant poulikakos", "poulikakos et al", "2011 reviewed", "reviewed in lito", "in lito et", "lito et al", "braf is mutated in", "is mutated in about", "mutated in about 8%", "in about 8% of", "about 8% of human", "8% of human cancers", "human cancers with", "cancers with high", "with high prevalence in", "high prevalence in hairy", "prevalence in hairy cell", "in hairy cell leukemia", "cell leukemia melanoma", "melanoma papillary thyroid", "papillary thyroid and ovarian", "thyroid and ovarian carcinomas", "ovarian carcinomas colorectal", "carcinomas colorectal cancer", "colorectal cancer and a", "cancer and a variety", "and a variety of", "a variety of other", "variety of other tumors", "other tumors davies", "tumors davies et", "et al 2002", "2002 reviewed in", "reviewed in samatar and", "in samatar and poulikakos", "and poulikakos 2014", "poulikakos 2014 .", "2014 . most braf", ". most braf mutations", "most braf mutations fall", "braf mutations fall in", "mutations fall in the", "fall in the activation", "in the activation loop", "the activation loop region", "activation loop region of", "loop region of the", "region of the kinase", "of the kinase or", "the kinase or the", "kinase or the adjacent", "or the adjacent glycine", "the adjacent glycine rich", "adjacent glycine rich region.", "glycine rich region. these", "rich region. these mutations", "region. these mutations promote", "these mutations promote increased", "mutations promote increased kinase", "promote increased kinase activity", "increased kinase activity either", "kinase activity either by", "activity either by mimicking", "either by mimicking the", "by mimicking the effects", "mimicking the effects of", "the effects of activation", "effects of activation loop", "of activation loop phosphorylations", "activation loop phosphorylations or", "loop phosphorylations or by", "phosphorylations or by promoting", "or by promoting the", "by promoting the active", "promoting the active conformation", "the active conformation of", "active conformation of the", "conformation of the enzyme", "the enzyme davies", "enzyme davies et", "2002 wan et", "et al 2004", "al 2004 .", "2004 . roughly 90%", ". roughly 90% of", "roughly 90% of braf", "90% of braf mutants", "of braf mutants are", "braf mutants are represented", "mutants are represented by", "are represented by the", "represented by the single", "by the single missense", "the single missense mutation", "single missense mutation braf", "missense mutation braf v600e", "braf v600e davies", "v600e davies et", "2004 . other highly", ". other highly active", "other highly active kinase", "highly active kinase mutants", "active kinase mutants of", "kinase mutants of braf", "mutants of braf include", "of braf include braf", "braf include braf g469a", "include braf g469a and", "braf g469a and braf", "g469a and braf t599dup.", "and braf t599dup. g469", "braf t599dup. g469 is", "t599dup. g469 is in", "g469 is in the", "is in the glycine", "in the glycine rich", "the glycine rich region", "glycine rich region of", "rich region of the", "of the kinase domain", "the kinase domain which", "kinase domain which plays", "domain which plays a", "which plays a role", "plays a role in", "a role in orienting", "role in orienting atp", "in orienting atp for", "orienting atp for catalysis", "for catalysis while", "catalysis while t599", "while t599 is one", "t599 is one of", "is one of the", "one of the two", "of the two conserved", "the two conserved regulatory", "two conserved regulatory phosphorylation", "conserved regulatory phosphorylation sites", "regulatory phosphorylation sites of", "phosphorylation sites of the", "sites of the activation", "of the activation loop.", "the activation loop. each", "activation loop. each of", "loop. each of these", "each of these mutants", "of these mutants has", "these mutants has highly", "mutants has highly enhanced", "has highly enhanced basal", "highly enhanced basal kinase", "enhanced basal kinase activities", "kinase activities phosphorylates", "activities phosphorylates mek", "phosphorylates mek and erk", "mek and erk in", "and erk in vitro", "erk in vitro and", "in vitro and in", "vitro and in vivo", "and in vivo and", "in vivo and is", "vivo and is transforming", "and is transforming when", "is transforming when expressed", "transforming when expressed in", "when expressed in vivo", "in vivo davies", "vivo davies et", "2004 eisenhardt et", "et al 2011", "al 2011 .", "2011 . further functional", ". further functional characterization", "further functional characterization shows", "functional characterization shows that", "characterization shows that these", "shows that these highly", "that these highly active", "these highly active mutants", "highly active mutants are", "active mutants are largely", "mutants are largely resistant", "are largely resistant to", "largely resistant to disruption", "resistant to disruption of", "to disruption of the", "disruption of the braf", "of the braf dimer", "the braf dimer interface", "dimer interface suggesting", "interface suggesting that", "suggesting that they are", "that they are able", "they are able to", "are able to act", "able to act as", "to act as monomers", "as monomers roring", "monomers roring et", "et al 2012", "2012 brummer et", "et al 2006", "2006 freeman et", "et al 2013", "2013 garnett et", "et al 2005", "al 2005 .", "2005 . activating braf", ". activating braf mutations", "activating braf mutations occur", "braf mutations occur for", "mutations occur for the", "occur for the most", "for the most part", "the most part independently", "most part independently of", "part independently of ras", "independently of ras activating", "of ras activating mutations", "activating mutations and", "mutations and ras", "and ras activity levels", "ras activity levels are", "activity levels are generally", "levels are generally low", "are generally low in", "generally low in braf", "low in braf mutant", "in braf mutant cells.", "braf mutant cells. moreover", "cells. moreover the", "moreover the kinase", "the kinase activity of", "kinase activity of these", "activity of these mutants", "of these mutants is", "these mutants is only", "mutants is only slightly", "is only slightly elevated", "only slightly elevated by", "slightly elevated by coexpression", "elevated by coexpression of", "by coexpression of g12v", "coexpression of g12v kras", "g12v kras and", "kras and biological", "and biological activity of", "biological activity of the", "activity of the highly", "of the highly active", "the highly active braf", "highly active braf mutants", "active braf mutants is", "braf mutants is independent", "mutants is independent of", "is independent of ras", "independent of ras binding", "ras binding brummer", "binding brummer et", "2006 wan et", "2004 davies et", "2002 garnett et", "2005 . although braf", ". although braf v600e", "although braf v600e is", "braf v600e is inhibited", "v600e is inhibited by", "is inhibited by raf", "inhibited by raf inhibitors", "by raf inhibitors such", "raf inhibitors such as", "inhibitors such as vemurafenib", "as vemurafenib resistance", "vemurafenib resistance frequently", "frequently develops in", "develops in some", "in some cases mediated", "some cases mediated by", "cases mediated by the", "mediated by the expression", "by the expression of", "the expression of a", "expression of a splice", "of a splice variant", "a splice variant that", "splice variant that lacks", "variant that lacks the", "that lacks the ras", "lacks the ras binding", "the ras binding domain", "ras binding domain and", "binding domain and shows", "domain and shows elevated", "and shows elevated dimerization", "shows elevated dimerization compared", "elevated dimerization compared to", "dimerization compared to the", "compared to the full", "to the full length", "the full length v600e", "full length v600e mutant", "v600e mutant poulikakos", "mutant poulikakos et", "2011 reviewed in", "reviewed in lito et", "in lito et al", "al 2013 .", "braf is mutated in about", "is mutated in about 8%", "mutated in about 8% of", "in about 8% of human", "about 8% of human cancers", "of human cancers with", "human cancers with high", "cancers with high prevalence", "with high prevalence in hairy", "high prevalence in hairy cell", "prevalence in hairy cell leukemia", "hairy cell leukemia melanoma", "leukemia melanoma papillary", "melanoma papillary thyroid and", "papillary thyroid and ovarian carcinomas", "and ovarian carcinomas colorectal", "ovarian carcinomas colorectal cancer", "carcinomas colorectal cancer and", "colorectal cancer and a variety", "cancer and a variety of", "and a variety of other", "a variety of other tumors", "of other tumors davies", "other tumors davies et", "tumors davies et al", "davies et al 2002", "al 2002 reviewed", "2002 reviewed in samatar", "reviewed in samatar and poulikakos", "samatar and poulikakos 2014", "and poulikakos 2014 .", "poulikakos 2014 . most", "2014 . most braf mutations", ". most braf mutations fall", "most braf mutations fall in", "braf mutations fall in the", "mutations fall in the activation", "fall in the activation loop", "in the activation loop region", "the activation loop region of", "activation loop region of the", "loop region of the kinase", "region of the kinase or", "of the kinase or the", "the kinase or the adjacent", "kinase or the adjacent glycine", "or the adjacent glycine rich", "the adjacent glycine rich region.", "adjacent glycine rich region. these", "glycine rich region. these mutations", "rich region. these mutations promote", "region. these mutations promote increased", "these mutations promote increased kinase", "mutations promote increased kinase activity", "promote increased kinase activity either", "increased kinase activity either by", "kinase activity either by mimicking", "activity either by mimicking the", "either by mimicking the effects", "by mimicking the effects of", "mimicking the effects of activation", "the effects of activation loop", "effects of activation loop phosphorylations", "of activation loop phosphorylations or", "activation loop phosphorylations or by", "loop phosphorylations or by promoting", "phosphorylations or by promoting the", "or by promoting the active", "by promoting the active conformation", "promoting the active conformation of", "the active conformation of the", "active conformation of the enzyme", "of the enzyme davies", "the enzyme davies et", "enzyme davies et al", "al 2002 wan", "2002 wan et al", "wan et al 2004", "et al 2004 .", "al 2004 . roughly", "2004 . roughly 90% of", ". roughly 90% of braf", "roughly 90% of braf mutants", "90% of braf mutants are", "of braf mutants are represented", "braf mutants are represented by", "mutants are represented by the", "are represented by the single", "represented by the single missense", "by the single missense mutation", "the single missense mutation braf", "single missense mutation braf v600e", "mutation braf v600e davies", "braf v600e davies et", "v600e davies et al", "al 2004 . other", "2004 . other highly active", ". other highly active kinase", "other highly active kinase mutants", "highly active kinase mutants of", "active kinase mutants of braf", "kinase mutants of braf include", "mutants of braf include braf", "of braf include braf g469a", "braf include braf g469a and", "include braf g469a and braf", "braf g469a and braf t599dup.", "g469a and braf t599dup. g469", "and braf t599dup. g469 is", "braf t599dup. g469 is in", "t599dup. g469 is in the", "g469 is in the glycine", "is in the glycine rich", "in the glycine rich region", "the glycine rich region of", "glycine rich region of the", "rich region of the kinase", "region of the kinase domain", "of the kinase domain which", "the kinase domain which plays", "kinase domain which plays a", "domain which plays a role", "which plays a role in", "plays a role in orienting", "a role in orienting atp", "role in orienting atp for", "in orienting atp for catalysis", "atp for catalysis while", "for catalysis while t599", "catalysis while t599 is", "while t599 is one of", "t599 is one of the", "is one of the two", "one of the two conserved", "of the two conserved regulatory", "the two conserved regulatory phosphorylation", "two conserved regulatory phosphorylation sites", "conserved regulatory phosphorylation sites of", "regulatory phosphorylation sites of the", "phosphorylation sites of the activation", "sites of the activation loop.", "of the activation loop. each", "the activation loop. each of", "activation loop. each of these", "loop. each of these mutants", "each of these mutants has", "of these mutants has highly", "these mutants has highly enhanced", "mutants has highly enhanced basal", "has highly enhanced basal kinase", "highly enhanced basal kinase activities", "basal kinase activities phosphorylates", "kinase activities phosphorylates mek", "activities phosphorylates mek and", "phosphorylates mek and erk in", "mek and erk in vitro", "and erk in vitro and", "erk in vitro and in", "in vitro and in vivo", "vitro and in vivo and", "and in vivo and is", "in vivo and is transforming", "vivo and is transforming when", "and is transforming when expressed", "is transforming when expressed in", "transforming when expressed in vivo", "expressed in vivo davies", "in vivo davies et", "vivo davies et al", "al 2004 eisenhardt", "2004 eisenhardt et al", "eisenhardt et al 2011", "et al 2011 .", "al 2011 . further", "2011 . further functional characterization", ". further functional characterization shows", "further functional characterization shows that", "functional characterization shows that these", "characterization shows that these highly", "shows that these highly active", "that these highly active mutants", "these highly active mutants are", "highly active mutants are largely", "active mutants are largely resistant", "mutants are largely resistant to", "are largely resistant to disruption", "largely resistant to disruption of", "resistant to disruption of the", "to disruption of the braf", "disruption of the braf dimer", "of the braf dimer interface", "braf dimer interface suggesting", "dimer interface suggesting that", "interface suggesting that they", "suggesting that they are able", "that they are able to", "they are able to act", "are able to act as", "able to act as monomers", "act as monomers roring", "as monomers roring et", "monomers roring et al", "roring et al 2012", "al 2012 brummer", "2012 brummer et al", "brummer et al 2006", "al 2006 freeman", "2006 freeman et al", "freeman et al 2013", "al 2013 garnett", "2013 garnett et al", "garnett et al 2005", "et al 2005 .", "al 2005 . activating", "2005 . activating braf mutations", ". activating braf mutations occur", "activating braf mutations occur for", "braf mutations occur for the", "mutations occur for the most", "occur for the most part", "for the most part independently", "the most part independently of", "most part independently of ras", "part independently of ras activating", "independently of ras activating mutations", "ras activating mutations and", "activating mutations and ras", "mutations and ras activity", "and ras activity levels are", "ras activity levels are generally", "activity levels are generally low", "levels are generally low in", "are generally low in braf", "generally low in braf mutant", "low in braf mutant cells.", "in braf mutant cells. moreover", "mutant cells. moreover the", "cells. moreover the kinase", "moreover the kinase activity", "the kinase activity of these", "kinase activity of these mutants", "activity of these mutants is", "of these mutants is only", "these mutants is only slightly", "mutants is only slightly elevated", "is only slightly elevated by", "only slightly elevated by coexpression", "slightly elevated by coexpression of", "elevated by coexpression of g12v", "by coexpression of g12v kras", "of g12v kras and", "g12v kras and biological", "kras and biological activity", "and biological activity of the", "biological activity of the highly", "activity of the highly active", "of the highly active braf", "the highly active braf mutants", "highly active braf mutants is", "active braf mutants is independent", "braf mutants is independent of", "mutants is independent of ras", "is independent of ras binding", "of ras binding brummer", "ras binding brummer et", "binding brummer et al", "al 2006 wan", "2006 wan et al", "al 2004 davies", "2004 davies et al", "al 2002 garnett", "2002 garnett et al", "al 2005 . although", "2005 . although braf v600e", ". although braf v600e is", "although braf v600e is inhibited", "braf v600e is inhibited by", "v600e is inhibited by raf", "is inhibited by raf inhibitors", "inhibited by raf inhibitors such", "by raf inhibitors such as", "raf inhibitors such as vemurafenib", "such as vemurafenib resistance", "as 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"presence of the", "of the braf", "the braf v600e", "braf v600e mutant", "mutant paradoxical", "activation of erk", "of erk signaling", "erk signaling has", "signaling has been", "has been observed", "been observed after", "observed after treatment", "after treatment of", "treatment of cells", "of cells with", "cells with inhibitor", "with inhibitor in", "inhibitor in the", "presence of wt", "of wt braf", "braf wan", "wan et al", "al 2004", "2004 garnett", "garnett et al", "al 2005", "2005 heidorn", "heidorn et al", "al 2010", "2010 hazivassiliou", "hazivassiliou et al", "2010 poulikakos", "poulikakos et al", "2010 . this", ". this paradoxical", "this paradoxical erk", "paradoxical erk activation", "erk activation is", "activation is also", "is also seen", "also seen in", "seen in cells", "in cells expressing", "cells expressing kinase", "expressing kinase dead", "kinase dead or", "dead or impaired", "or impaired versions", "impaired versions of", "versions of braf", "of braf such", "braf such as", "such as d594v", "d594v which", "which occur with", "occur with low", "with low frequency", "low frequency in", "frequency in some", "in some cancers", "cancers wan", "2004 heidorn", ". unlike", "unlike braf v600e", "v600e which", "which occurs exclusively", "occurs exclusively of", "exclusively of activating", "of activating ras", "activating ras mutations", "mutations kinase", "kinase impaired versions", "of braf are", "braf are coincident", "are coincident with", "coincident with ras", "with ras mutations", "ras mutations in", "mutations in human", "in human cancers", "cancers and", "indeed paradoxical", "erk signaling in", "signaling in the", "presence of inactive", "of inactive braf", "inactive braf is", "braf is enhanced", "is enhanced in", "enhanced in the", "presence of oncogenic", "of oncogenic ras", "ras heidorn", "2010 reviewed", "reviewed in holderfield", "in holderfield et", "holderfield et al", "al 2014", ". although", "although the details", "the details remain", "details remain to", "remain to be", "to be worked", "be worked out", "out paradoxical", "erk activation in", "inactive braf appears", "braf appears to", "appears to rely", "to rely on", "rely on enhanced", "on enhanced dimerization", "enhanced dimerization with", "dimerization with and", "with and transactivation", "and transactivation of", "transactivation of craf", "craf heidorn", "roring et al", "al 2012", "2012 rajakulendran", "rajakulendran et al", "al 2009", "2009 holderfield", "al 2013", "2013 freeman", "freeman et al", "2013 reviewed", "reviewed in roskoski", "roskoski 2010", "2010 samatar", "samatar and poulikakos", "poulikakos 2014", "2014 lavoie", "lavoie and therrien", "therrien 2015", "2015 . raf", ". raf inhibitors", "raf inhibitors can", "inhibitors can promote", "can promote association", "promote association of", "association of raf", "of raf ras", "raf ras interaction", "ras interaction and", "interaction and enhanced", "and enhanced raf", "enhanced raf dimerization", "raf dimerization through", "dimerization through disruption", "through disruption of", "disruption of intramolecular", "of intramolecular interactions", "intramolecular interactions between", "interactions between the", "between the kinase", "the kinase domain", "kinase domain and", "domain and its", "and its n", "its n terminal", "n terminal regulatory", "terminal regulatory region.", "regulatory region. moreover", "moreover specific", "specific braf inhibitors", "braf inhibitors can", "inhibitors can only", "can only occupy", "only occupy one", "occupy one protomer", "one protomer within", "protomer within the", "within the transcactivated", "the transcactivated braf", "transcactivated braf dimer", "braf dimer due", "dimer due to", "due to negative", "to negative co", "negative co operativity", "co operativity leading", "operativity leading to", "leading to paradoxical", "to paradoxical erk", "paradoxical erk activation.", "activation. karoulia", "karoulia et al", "al 2016", "2016 jin", "jin et al", "al 2017", "2017 reviewed", "reviewed in karoulia", "in karoulia et", "while braf specific inhibitors", "braf specific inhibitors inhibit", "specific inhibitors inhibit mapk/erk", "inhibitors inhibit mapk/erk activation", "inhibit mapk/erk activation in", "mapk/erk activation in the", "activation in the presence", "in the presence of", "the presence of the", "presence of the braf", "of the braf v600e", "the braf v600e mutant", "v600e mutant paradoxical", "mutant paradoxical activation", "paradoxical activation of erk", "activation of erk signaling", "of erk signaling has", "erk signaling has been", "signaling has been observed", "has been observed after", "been observed after treatment", "observed after treatment of", "after treatment of cells", "treatment of cells with", "of cells with inhibitor", "cells with inhibitor in", "with inhibitor in the", "inhibitor in the presence", "the presence of wt", "presence of wt braf", "wt braf wan", "braf wan et", "et al 2004", "2004 garnett et", "et al 2005", "2005 heidorn et", "et al 2010", "2010 hazivassiliou et", "2010 poulikakos et", "al 2010 .", "2010 . this paradoxical", ". this paradoxical erk", "this paradoxical erk activation", "paradoxical erk activation is", "erk activation is also", "activation is also seen", "is also seen in", "also seen in cells", "seen in cells expressing", "in cells expressing kinase", "cells expressing kinase dead", "expressing kinase dead or", "kinase dead or impaired", "dead or impaired versions", "or impaired versions of", "impaired versions of braf", "versions of braf such", "of braf such as", "braf such as d594v", "as d594v which", "d594v which occur", "which occur with low", "occur with low frequency", "with low frequency in", "low frequency in some", "frequency in some cancers", "some cancers wan", "cancers wan et", "2004 heidorn et", "2010 . unlike", ". unlike braf", "braf v600e which", "v600e which occurs", "which occurs exclusively of", "occurs exclusively of activating", "exclusively of activating ras", "of activating ras mutations", "ras mutations kinase", "mutations kinase impaired", "kinase impaired versions of", "versions of braf are", "of braf are coincident", "braf are coincident with", "are coincident with ras", "coincident with ras mutations", "with ras mutations in", "ras mutations in human", "mutations in human cancers", "human cancers and", "cancers and indeed", "and indeed paradoxical", "indeed paradoxical activation", "of erk signaling in", "erk signaling in the", "signaling in the presence", "the presence of inactive", "presence of inactive braf", "of inactive braf is", "inactive braf is enhanced", "braf is enhanced in", "is enhanced in the", "enhanced in the presence", "the presence of oncogenic", "presence of oncogenic ras", "oncogenic ras heidorn", "ras heidorn et", "2010 reviewed in", "reviewed in holderfield et", "in holderfield et al", "et al 2014", "al 2014 .", "2014 . although", ". although the", "although the details remain", "the details remain to", "details remain to be", "remain to be worked", "to be worked out", "worked out paradoxical", "out paradoxical erk", "paradoxical erk activation in", "erk activation in the", "of inactive braf appears", "inactive braf appears to", "braf appears to rely", "appears to rely on", "to rely on enhanced", "rely on enhanced dimerization", "on enhanced dimerization with", "enhanced dimerization with and", "dimerization with and transactivation", "with and transactivation of", "and transactivation of craf", "of craf heidorn", "craf heidorn et", "2010 roring", "et al 2012", "2012 rajakulendran et", "et al 2009", "2009 holderfield et", "et al 2013", "2013 freeman et", "2013 reviewed in", "in roskoski 2010", "2010 samatar and", "and poulikakos 2014", "2014 lavoie and", "and therrien 2015", "therrien 2015 .", "2015 . raf inhibitors", ". raf inhibitors can", "raf inhibitors can promote", "inhibitors can promote association", "can promote association of", "promote association of raf", "association of raf ras", "of raf ras interaction", "raf ras interaction and", "ras interaction and enhanced", "interaction and enhanced raf", "and enhanced raf dimerization", "enhanced raf dimerization through", "raf dimerization through disruption", "dimerization through disruption of", "through disruption of intramolecular", "disruption of intramolecular interactions", "of intramolecular interactions between", "intramolecular interactions between the", "interactions between the kinase", "between the kinase domain", "the kinase domain and", "kinase domain and its", "domain and its n", "and its n terminal", "its n terminal regulatory", "n terminal regulatory region.", "terminal regulatory region. moreover", "region. moreover specific", "moreover specific braf", "specific braf inhibitors can", "braf inhibitors can only", "inhibitors can only occupy", "can only occupy one", "only occupy one protomer", "occupy one protomer within", "one protomer within the", "protomer within the transcactivated", "within the transcactivated braf", "the transcactivated braf dimer", "transcactivated braf dimer due", "braf dimer due to", "dimer due to negative", "due to negative co", "to negative co operativity", "negative co operativity leading", "co operativity leading to", "operativity leading to paradoxical", "leading to paradoxical erk", "to paradoxical erk activation.", "erk activation. karoulia", "activation. karoulia et", "et al 2016", "2016 jin et", "et al 2017", "2017 reviewed in", "reviewed in karoulia et", "in karoulia et al", "al 2017 .", "while braf specific inhibitors inhibit", "braf specific inhibitors inhibit mapk/erk", "specific inhibitors inhibit mapk/erk activation", "inhibitors inhibit mapk/erk activation in", "inhibit mapk/erk activation in the", "mapk/erk activation in the presence", "activation in the presence of", "in the presence of the", "the presence of the braf", "presence of the braf v600e", "of the braf v600e mutant", "braf v600e mutant paradoxical", "v600e mutant paradoxical activation", "mutant paradoxical activation of", "paradoxical activation of erk signaling", "activation of erk signaling has", "of erk signaling has been", "erk signaling has been observed", "signaling has been observed after", "has been observed after treatment", "been observed after treatment of", "observed after treatment of cells", "after treatment of cells with", "treatment of cells with inhibitor", "of cells with inhibitor in", "cells with inhibitor in the", "with inhibitor in the presence", "inhibitor in the presence of", "in the presence of wt", "the presence of wt braf", "of wt braf wan", "wt braf wan et", "braf wan et al", "wan et al 2004", "al 2004 garnett", "2004 garnett et al", "garnett et al 2005", "al 2005 heidorn", "2005 heidorn et al", "heidorn et al 2010", "al 2010 hazivassiliou", "2010 hazivassiliou et al", "hazivassiliou et al 2010", "al 2010 poulikakos", "2010 poulikakos et al", "poulikakos et al 2010", "et al 2010 .", "al 2010 . this", "2010 . this paradoxical erk", ". this paradoxical erk activation", "this paradoxical erk activation is", "paradoxical erk activation is also", "erk activation is also seen", "activation is also seen in", "is also seen in cells", "also seen in cells expressing", "seen in cells expressing kinase", "in cells expressing kinase dead", "cells expressing kinase dead or", "expressing kinase dead or impaired", "kinase dead or impaired versions", "dead or impaired versions of", "or impaired versions of braf", "impaired versions of braf such", "versions of braf such as", "of braf such as d594v", "such as d594v which", "as d594v which occur", "d594v which occur with", "which occur with low frequency", "occur with low frequency in", "with low frequency in some", "low frequency in some cancers", "in some cancers wan", "some cancers wan et", "cancers wan et al", "al 2004 heidorn", "2004 heidorn et al", "2010 . unlike braf", ". unlike braf v600e", "unlike braf v600e which", "braf v600e which occurs", "v600e which occurs exclusively", "which occurs exclusively of activating", "occurs exclusively of activating ras", "exclusively of activating ras mutations", "activating ras mutations kinase", "ras mutations kinase impaired", "mutations kinase impaired versions", "kinase impaired versions of braf", "impaired versions of braf are", "versions of braf are coincident", "of braf are coincident with", "braf are coincident with ras", "are coincident with ras mutations", "coincident with ras mutations in", "with ras mutations in human", "ras mutations in human cancers", "in human cancers and", "human cancers and indeed", "and indeed paradoxical activation", "indeed paradoxical activation of", "activation of erk signaling in", "of erk signaling in the", "erk signaling in the presence", "signaling in the presence of", "in the presence of inactive", "the presence of inactive braf", "presence of inactive braf is", "of inactive braf is enhanced", "inactive braf is enhanced in", "braf is enhanced in the", "is enhanced in the presence", "enhanced in the presence of", "in the presence of oncogenic", "the presence of oncogenic ras", "of oncogenic ras heidorn", "oncogenic ras heidorn et", "ras heidorn et al", "al 2010 reviewed", "2010 reviewed in holderfield", "reviewed in holderfield et al", "holderfield et al 2014", "et al 2014 .", "2014 . although the", ". although the details", "although the details remain to", "the details remain to be", "details remain to be worked", "remain to be worked out", "be worked out paradoxical", "worked out paradoxical erk", "out paradoxical erk activation", "paradoxical erk activation in the", "erk activation in the presence", "presence of inactive braf appears", "of inactive braf appears to", "inactive braf appears to rely", "braf appears to rely on", "appears to rely on enhanced", "to rely on enhanced dimerization", "rely on enhanced dimerization with", "on enhanced dimerization with and", "enhanced dimerization with and transactivation", "dimerization with and transactivation of", "with and transactivation of craf", "transactivation of craf heidorn", "of craf heidorn et", "craf heidorn et al", "2010 roring et", "roring et al 2012", "al 2012 rajakulendran", "2012 rajakulendran et al", "rajakulendran et al 2009", "al 2009 holderfield", "2009 holderfield et al", "holderfield et al 2013", "al 2013 freeman", "2013 freeman et al", "freeman et al 2013", "al 2013 reviewed", "2013 reviewed in roskoski", "reviewed in roskoski 2010", "roskoski 2010 samatar", "2010 samatar and poulikakos", "samatar and poulikakos 2014", "poulikakos 2014 lavoie", "2014 lavoie and therrien", "lavoie and therrien 2015", "and therrien 2015 .", "therrien 2015 . raf", "2015 . raf inhibitors can", ". raf inhibitors can promote", "raf inhibitors can promote association", "inhibitors can promote association of", "can promote association of raf", "promote association of raf ras", "association of raf ras interaction", "of raf ras interaction and", "raf ras interaction and enhanced", "ras interaction and enhanced raf", "interaction and enhanced raf dimerization", "and enhanced raf dimerization through", "enhanced raf dimerization through disruption", "raf dimerization through disruption of", "dimerization through disruption of intramolecular", "through disruption of intramolecular interactions", "disruption of intramolecular interactions between", "of intramolecular interactions between the", "intramolecular interactions between the kinase", "interactions between the kinase domain", "between the kinase domain and", "the kinase domain and its", "kinase domain and its n", "domain and its n terminal", "and its n terminal regulatory", "its n terminal regulatory region.", "n terminal regulatory region. moreover", "regulatory region. moreover specific", "region. moreover specific braf", "moreover specific braf inhibitors", "specific braf inhibitors can only", "braf inhibitors can only occupy", "inhibitors can only occupy one", "can only occupy one protomer", "only occupy one protomer within", "occupy one protomer within the", "one protomer within the transcactivated", "protomer within the transcactivated braf", "within the transcactivated braf dimer", "the transcactivated braf dimer due", "transcactivated braf dimer due to", "braf dimer due to negative", "dimer due to negative co", "due to negative co operativity", "to negative co operativity leading", "negative co operativity leading to", "co operativity leading to paradoxical", "operativity leading to paradoxical erk", "leading to paradoxical erk activation.", "paradoxical erk activation. karoulia", "erk activation. karoulia et", "activation. karoulia et al", "karoulia et al 2016", "al 2016 jin", "2016 jin et al", "jin et al 2017", "al 2017 reviewed", "2017 reviewed in karoulia", "reviewed in karoulia et al", "karoulia et al 2017", "et al 2017 ." ] }, { "record_id": "GLY_000594_1_1092", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6803157", "r hsa", "hsa 6803157", "r hsa 6803157" ] }, { "record_id": "GLY_000594_1_1092", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "antimicrobial peptides", "are small", "small molecular", "molecular weight", "weight proteins", "proteins with", "with broad", "broad spectrum", "spectrum of", "of antimicrobial", "antimicrobial activity", "activity against", "against bacteria", "and fungi", "zasloff m", "m 2002", "radek k", "k &", "& gallo", "gallo r", "r 2007", "2007 .", ". the", "the majority", "majority of", "of known", "known amps", "amps are", "are cationic", "cationic peptides", "peptides with", "with common", "common structural", "structural characteristics", "characteristics where", "where domains", "domains of", "of hydrophobic", "hydrophobic and", "and cationic", "cationic amino", "amino acids", "acids are", "are spatially", "spatially arranged", "arranged into", "into an", "an amphipathic", "amphipathic design", "which facilitates", "facilitates their", "their interaction", "interaction with", "with bacterial", "bacterial membranes", "shai y", "y 2002", "yeaman mr", "mr &", "& yount", "yount ny", "ny 2003", "brown kl", "kl &", "& hancock", "hancock re", "re 2006", "dennison sr", "sr et", "et al.", "al. 2005", "zelezetsky i", "i &", "& tossi", "tossi a", "a 2006", "2006 .", ". it", "it is", "is generally", "generally excepted", "excepted that", "that the", "the electrostatic", "electrostatic interaction", "interaction facilitates", "facilitates the", "the initial", "initial binding", "binding of", "of the", "the positively", "positively charged", "charged peptides", "peptides to", "to the", "the negatively", "negatively charged", "charged bacterial", "bacterial membrane.", "membrane. moreover", "the structural", "structural amphiphilicity", "amphiphilicity of", "of amps", "amps is", "is thought", "thought to", "to promote", "promote their", "their integration", "integration into", "into lipid", "lipid bilayers", "bilayers of", "of pathogenic", "pathogenic cells", "leading to", "to membrane", "membrane disintegration", "disintegration and", "and finally", "finally to", "the microbial", "microbial cell", "cell death.", "death. in", "in addition", "addition to", "to cationic", "cationic amps", "amps a", "a few", "few anionic", "anionic antimicrobial", "peptides have", "have been", "been found", "found in", "in humans", "however their", "their mechanism", "mechanism of", "of action", "action remains", "remains to", "to be", "be clarified", "lai y", "y et", "al. 2007", "harris f", "f et", "al. 2009", "paulmann m", "m et", "al. 2012", "2012 .", ". besides", "besides the", "the direct", "direct neutralizing", "neutralizing effects", "effects on", "on bacteria", "bacteria amps", "amps may", "may modulate", "modulate cells", "cells of", "the adaptive", "adaptive immunity", "t cells", "to control", "control inflammation", "inflammation and/or", "and/or to", "to increase", "increase bacterial", "bacterial clearance.

              amps", "clearance.

              amps have", "have also", "also been", "been referred", "referred to", "to as", "as cationic", "cationic host", "host defense", "defense peptides", "antimicrobial peptides/proteins", "cationic amphipathic", "amphipathic peptides", "peptides and", "and alpha", "alpha helical", "helical antimicrobial", "groenink j", "j et", "al. 1999", "bradshaw j", "j 2003", "riedl s", "s et", "al. 2011", "huang y", "al. 2010", "2010 .

              the", ".

              the reactome", "reactome module", "module describes", "describes the", "the interaction", "interaction events", "events of", "of various", "various types", "types of", "of human", "human amps", "such as", "as cathelicidin", "histatins and", "and neutrophil", "neutrophil serine", "serine proteases", "with conserved", "conserved patterns", "patterns of", "of microbial", "microbial membranes", "membranes at", "at the", "the host", "host pathogen", "pathogen interface.", "interface. the", "the module", "module includes", "includes also", "also proteolytic", "proteolytic processing", "processing events", "events for", "for dermcidin", "and cathelicidin", "that become", "become functional", "functional upon", "upon cleavage.", "cleavage. in", "module highlights", "highlights an", "an amp", "amp associated", "associated ability", "ability of", "host to", "control metal", "metal quota", "quota at", "at inflammation", "inflammation sites", "sites to", "to influence", "influence host", "pathogen interactions.", "peptides amps", "are small molecular", "small molecular weight", "molecular weight proteins", "weight proteins with", "proteins with broad", "with broad spectrum", "broad spectrum of", "spectrum of antimicrobial", "of antimicrobial activity", "antimicrobial activity against", "activity against bacteria", "bacteria viruses", "viruses and", "fungi zasloff", "zasloff m 2002", "2002 radek", "radek k &", "k & gallo", "& gallo r", "gallo r 2007", "r 2007 .", "2007 . the", ". the majority", "the majority of", "majority of known", "of known amps", "known amps are", "amps are cationic", "are cationic peptides", "cationic peptides with", "peptides with common", "with common structural", "common structural characteristics", "structural characteristics where", "characteristics where domains", "where domains of", "domains of hydrophobic", "of hydrophobic and", "hydrophobic and cationic", "and cationic amino", "cationic amino acids", "amino acids are", "acids are spatially", "are spatially arranged", "spatially arranged into", "arranged into an", "into an amphipathic", "an amphipathic design", "design which", "which facilitates their", "facilitates their interaction", "their interaction with", "interaction with bacterial", "with bacterial membranes", "membranes shai", "shai y 2002", "2002 yeaman", "yeaman mr &", "mr & yount", "& yount ny", "yount ny 2003", "2003 brown", "brown kl &", "kl & hancock", "& hancock re", "hancock re 2006", "2006 dennison", "dennison sr et", "sr et al.", "et al. 2005", "2005 zelezetsky", "zelezetsky i &", "i & tossi", "& tossi a", "tossi a 2006", "a 2006 .", "2006 . it", ". it is", "it is generally", "is generally excepted", "generally excepted that", "excepted that the", "that the electrostatic", "the electrostatic interaction", "electrostatic interaction facilitates", "interaction facilitates the", "facilitates the initial", "the initial binding", "initial binding of", "binding of the", "of the positively", "the positively charged", "positively charged peptides", "charged peptides to", "peptides to the", "to the negatively", "the negatively charged", "negatively charged bacterial", "charged bacterial membrane.", "bacterial membrane. moreover", "moreover the", "the structural amphiphilicity", "structural amphiphilicity of", "amphiphilicity of amps", "of amps is", "amps is thought", "is thought to", "thought to promote", "to promote their", "promote their integration", "their integration into", "integration into lipid", "into lipid bilayers", "lipid bilayers of", "bilayers of pathogenic", "of pathogenic cells", "cells leading", "leading to membrane", "to membrane disintegration", "membrane disintegration and", "disintegration and finally", "and finally to", "finally to the", "to the microbial", "the microbial cell", "microbial cell death.", "cell death. in", "death. in addition", "in addition to", "addition to cationic", "to cationic amps", "cationic amps a", "amps a few", "a few anionic", "few anionic antimicrobial", "anionic antimicrobial peptides", "antimicrobial peptides have", "peptides have been", "have been found", "been found in", "found in humans", "humans however", "however their mechanism", "their mechanism of", "mechanism of action", "of action remains", "action remains to", "remains to be", "to be clarified", "clarified lai", "lai y et", "y et al.", "et al. 2007", "2007 harris", "harris f et", "f et al.", "et al. 2009", "2009 paulmann", "paulmann m et", "m et al.", "et al. 2012", "al. 2012 .", "2012 . besides", ". besides the", "besides the direct", "the direct neutralizing", "direct neutralizing effects", "neutralizing effects on", "effects on bacteria", "on bacteria amps", "bacteria amps may", "amps may modulate", "may modulate cells", "modulate cells of", "cells of the", "of the adaptive", "the adaptive immunity", "immunity neutrophils", "neutrophils t", "cells macrophages", "macrophages to", "to control inflammation", "control inflammation and/or", "inflammation and/or to", "and/or to increase", "to increase bacterial", "increase bacterial clearance.

              amps", "bacterial clearance.

              amps have", "clearance.

              amps have also", "have also been", "also been referred", "been referred to", "referred to as", "to as cationic", "as cationic host", "cationic host defense", "host defense peptides", "peptides anionic", "anionic antimicrobial peptides/proteins", "peptides/proteins cationic", "cationic amphipathic peptides", "peptides cationic", "amps host", "defense peptides and", "peptides and alpha", "and alpha helical", "alpha helical antimicrobial", "helical antimicrobial peptides", "peptides brown", "2006 harris", "2009 groenink", "groenink j et", "j et al.", "et al. 1999", "1999 bradshaw", "bradshaw j 2003", "2003 riedl", "riedl s et", "s et al.", "et al. 2011", "2011 huang", "huang y et", "et al. 2010", "al. 2010 .

              the", "2010 .

              the reactome", ".

              the reactome module", "reactome module describes", "module describes the", "describes the interaction", "the interaction events", "interaction events of", "events of various", "of various types", "various types of", "types of human", "of human amps", "amps such", "such as cathelicidin", "cathelicidin histatins", "histatins and neutrophil", "and neutrophil serine", "neutrophil serine proteases", "proteases with", "with conserved patterns", "conserved patterns of", "patterns of microbial", "of microbial membranes", "microbial membranes at", "membranes at the", "at the host", "the host pathogen", "host pathogen interface.", "pathogen interface. the", "interface. the module", "the module includes", "module includes also", "includes also proteolytic", "also proteolytic processing", "proteolytic processing events", "processing events for", "events for dermcidin", "dermcidin dcd", "dcd and", "cathelicidin camp", "camp that", "that become functional", "become functional upon", "functional upon cleavage.", "upon cleavage. in", "cleavage. in addition", "addition the", "the module highlights", "module highlights an", "highlights an amp", "an amp associated", "amp associated ability", "associated ability of", "ability of the", "of the host", "the host to", "host to control", "to control metal", "control metal quota", "metal quota at", "quota at inflammation", "at inflammation sites", "inflammation sites to", "sites to influence", "to influence host", "influence host pathogen", "host pathogen interactions.", "antimicrobial peptides amps", "amps are small", "are small molecular weight", "small molecular weight proteins", "molecular weight proteins with", "weight proteins with broad", "proteins with broad spectrum", "with broad spectrum of", "broad spectrum of antimicrobial", "spectrum of antimicrobial activity", "of antimicrobial activity against", "antimicrobial activity against bacteria", "against bacteria viruses", "viruses and fungi", "and fungi zasloff", "fungi zasloff m", "m 2002 radek", "2002 radek k", "radek k & gallo", "k & gallo r", "& gallo r 2007", "gallo r 2007 .", "r 2007 . the", "2007 . the majority", ". the majority of", "the majority of known", "majority of known amps", "of known amps are", "known amps are cationic", "amps are cationic peptides", "are cationic peptides with", "cationic peptides with common", "peptides with common structural", "with common structural characteristics", "common structural characteristics where", "structural characteristics where domains", "characteristics where domains of", "where domains of hydrophobic", "domains of hydrophobic and", "of hydrophobic and cationic", "hydrophobic and cationic amino", "and cationic amino acids", "cationic amino acids are", "amino acids are spatially", "acids are spatially arranged", "are spatially arranged into", "spatially arranged into an", "arranged into an amphipathic", "into an amphipathic design", "amphipathic design which", "design which facilitates", "which facilitates their interaction", "facilitates their interaction with", "their interaction with bacterial", "interaction with bacterial membranes", "bacterial membranes shai", "membranes shai y", "y 2002 yeaman", "2002 yeaman mr", "yeaman mr & yount", "mr & yount ny", "& yount ny 2003", "ny 2003 brown", "2003 brown kl", "brown kl & hancock", "kl & hancock re", "& hancock re 2006", "re 2006 dennison", "2006 dennison sr", "dennison sr et al.", "sr et al. 2005", "al. 2005 zelezetsky", "2005 zelezetsky i", "zelezetsky i & tossi", "i & tossi a", "& tossi a 2006", "tossi a 2006 .", "a 2006 . it", "2006 . it is", ". it is generally", "it is generally excepted", "is generally excepted that", "generally excepted that the", "excepted that the electrostatic", "that the electrostatic interaction", "the electrostatic interaction facilitates", "electrostatic interaction facilitates the", "interaction facilitates the initial", "facilitates the initial binding", "the initial binding of", "initial binding of the", "binding of the positively", "of the positively charged", "the positively charged peptides", "positively charged peptides to", "charged peptides to the", "peptides to the negatively", "to the negatively charged", "the negatively charged bacterial", "negatively charged bacterial membrane.", "charged bacterial membrane. moreover", "membrane. moreover the", "moreover the structural", "the structural amphiphilicity of", "structural amphiphilicity of amps", "amphiphilicity of amps is", "of amps is thought", "amps is thought to", "is thought to promote", "thought to promote their", "to promote their integration", "promote their integration into", "their integration into lipid", "integration into lipid bilayers", "into lipid bilayers of", "lipid bilayers of pathogenic", "bilayers of pathogenic cells", "pathogenic cells leading", "cells leading to", "leading to membrane disintegration", "to membrane disintegration and", "membrane disintegration and finally", "disintegration and finally to", "and finally to the", "finally to the microbial", "to the microbial cell", "the microbial cell death.", "microbial cell death. in", "cell death. in addition", "death. in addition to", "in addition to cationic", "addition to cationic amps", "to cationic amps a", "cationic amps a few", "amps a few anionic", "a few anionic antimicrobial", "few anionic antimicrobial peptides", "anionic antimicrobial peptides have", "antimicrobial peptides have been", "peptides have been found", "have been found in", "been found in humans", "in humans however", "humans however their", "however their mechanism of", "their mechanism of action", "mechanism of action remains", "of action remains to", "action remains to be", "remains to be clarified", "be clarified lai", "clarified lai y", "lai y et al.", "y et al. 2007", "al. 2007 harris", "2007 harris f", "harris f et al.", "f et al. 2009", "al. 2009 paulmann", "2009 paulmann m", "paulmann m et al.", "m et al. 2012", "et al. 2012 .", "al. 2012 . besides", "2012 . besides the", ". besides the direct", "besides the direct neutralizing", "the direct neutralizing effects", "direct neutralizing effects on", "neutralizing effects on bacteria", "effects on bacteria amps", "on bacteria amps may", "bacteria amps may modulate", "amps may modulate cells", "may modulate cells of", "modulate cells of the", "cells of the adaptive", "of the adaptive immunity", "adaptive immunity neutrophils", "neutrophils t cells", "t cells macrophages", "macrophages to control", "to control inflammation and/or", "control inflammation and/or to", "inflammation and/or to increase", "and/or to increase bacterial", "to increase bacterial clearance.

              amps", "increase bacterial clearance.

              amps have", "bacterial clearance.

              amps have also", "clearance.

              amps have also been", "have also been referred", "also been referred to", "been referred to as", "referred to as cationic", "to as cationic host", "as cationic host defense", "cationic host defense peptides", "defense peptides anionic", "peptides anionic antimicrobial", "antimicrobial peptides/proteins cationic", "peptides/proteins cationic amphipathic", "amphipathic peptides cationic", "peptides cationic amps", "cationic amps host", "amps host defense", "host defense peptides and", "defense peptides and alpha", "peptides and alpha helical", "and alpha helical antimicrobial", "alpha helical antimicrobial peptides", "antimicrobial peptides brown", "peptides brown kl", "re 2006 harris", "2006 harris f", "al. 2009 groenink", "2009 groenink j", "groenink j et al.", "j et al. 1999", "al. 1999 bradshaw", "1999 bradshaw j", "j 2003 riedl", "2003 riedl s", "riedl s et al.", "s et al. 2011", "al. 2011 huang", "2011 huang y", "huang y et al.", "y et al. 2010", "et al. 2010 .

              the", "al. 2010 .

              the reactome", "2010 .

              the reactome module", ".

              the reactome module describes", "reactome module describes the", "module describes the interaction", "describes the interaction events", "the interaction events of", "interaction events of various", "events of various types", "of various types of", "various types of human", "types of human amps", "human amps such", "amps such as", "as cathelicidin histatins", "cathelicidin histatins and", "histatins and neutrophil serine", "and neutrophil serine proteases", "serine proteases with", "proteases with conserved", "with conserved patterns of", "conserved patterns of microbial", "patterns of microbial membranes", "of microbial membranes at", "microbial membranes at the", "membranes at the host", "at the host pathogen", "the host pathogen interface.", "host pathogen interface. the", "pathogen interface. the module", "interface. the module includes", "the module includes also", "module includes also proteolytic", "includes also proteolytic processing", "also proteolytic processing events", "proteolytic processing events for", "processing events for dermcidin", "for dermcidin dcd", "dcd and cathelicidin", "and cathelicidin camp", "camp that become", "that become functional upon", "become functional upon cleavage.", "functional upon cleavage. in", "upon cleavage. in addition", "in addition the", "addition the module", "the module highlights an", "module highlights an amp", "highlights an amp associated", "an amp associated ability", "amp associated ability of", "associated ability of the", "ability of the host", "of the host to", "the host to control", "host to control metal", "to control metal quota", "control metal quota at", "metal quota at inflammation", "quota at inflammation sites", "at inflammation sites to", "inflammation sites to influence", "sites to influence host", "to influence host pathogen", "influence host pathogen interactions.", "peptides amps are", "amps are small molecular", "are small molecular weight proteins", "small molecular weight proteins with", "molecular weight proteins with broad", "weight proteins with broad spectrum", "proteins with broad spectrum of", "with broad spectrum of antimicrobial", "broad spectrum of antimicrobial activity", "spectrum of antimicrobial activity against", "of antimicrobial activity against bacteria", "activity against bacteria viruses", "bacteria viruses and", "and fungi zasloff m", "fungi zasloff m 2002", "zasloff m 2002 radek", "m 2002 radek k", "2002 radek k &", "radek k & gallo r", "k & gallo r 2007", "& gallo r 2007 .", "gallo r 2007 . the", "r 2007 . the majority", "2007 . the majority of", ". the majority of known", "the majority of known amps", "majority of known amps are", "of known amps are cationic", "known amps are cationic peptides", "amps are cationic peptides with", "are cationic peptides with common", "cationic peptides with common structural", "peptides with common structural characteristics", "with common structural characteristics where", "common structural characteristics where domains", "structural characteristics where domains of", "characteristics where domains of hydrophobic", "where domains of hydrophobic and", "domains of hydrophobic and cationic", "of hydrophobic and cationic amino", "hydrophobic and cationic amino acids", "and cationic amino acids are", "cationic amino acids are spatially", "amino acids are spatially arranged", "acids are spatially arranged into", "are spatially arranged into an", "spatially arranged into an amphipathic", "arranged into an amphipathic design", "an amphipathic design which", "amphipathic design which facilitates", "design which facilitates their", "which facilitates their interaction with", "facilitates their interaction with bacterial", "their interaction with bacterial membranes", "with bacterial membranes shai", "bacterial membranes shai y", "membranes shai y 2002", "shai y 2002 yeaman", "y 2002 yeaman mr", "2002 yeaman mr &", "yeaman mr & yount ny", "mr & yount ny 2003", "yount ny 2003 brown", "ny 2003 brown kl", "2003 brown kl &", "brown kl & hancock re", "kl & hancock re 2006", "hancock re 2006 dennison", "re 2006 dennison sr", "2006 dennison sr et", "dennison sr et al. 2005", "et al. 2005 zelezetsky", "al. 2005 zelezetsky i", "2005 zelezetsky i &", "zelezetsky i & tossi a", "i & tossi a 2006", "& tossi a 2006 .", "tossi a 2006 . it", "a 2006 . it is", "2006 . it is generally", ". it is generally excepted", "it is generally excepted that", "is generally excepted that the", "generally excepted that the electrostatic", "excepted that the electrostatic interaction", "that the electrostatic interaction facilitates", "the electrostatic interaction facilitates the", "electrostatic interaction facilitates the initial", "interaction facilitates the initial binding", "facilitates the initial binding of", "the initial binding of the", "initial binding of the positively", "binding of the positively charged", "of the positively charged peptides", "the positively charged peptides to", "positively charged peptides to the", "charged peptides to the negatively", "peptides to the negatively charged", "to the negatively charged bacterial", "the negatively charged bacterial membrane.", "negatively charged bacterial membrane. moreover", "bacterial membrane. moreover the", "membrane. moreover the structural", "moreover the structural amphiphilicity", "the structural amphiphilicity of amps", "structural amphiphilicity of amps is", "amphiphilicity of amps is thought", "of amps is thought to", "amps is thought to promote", "is thought to promote their", "thought to promote their integration", "to promote their integration into", "promote their integration into lipid", "their integration into lipid bilayers", "integration into lipid bilayers of", "into lipid bilayers of pathogenic", "lipid bilayers of pathogenic cells", "of pathogenic cells leading", "pathogenic cells leading to", "cells leading to membrane", "leading to membrane disintegration and", "to membrane disintegration and finally", "membrane disintegration and finally to", "disintegration and finally to the", "and finally to the microbial", "finally to the microbial cell", "to the microbial cell death.", "the microbial cell death. in", "microbial cell death. in addition", "cell death. in addition to", "death. in addition to cationic", "in addition to cationic amps", "addition to cationic amps a", "to cationic amps a few", "cationic amps a few anionic", "amps a few anionic antimicrobial", "a few anionic antimicrobial peptides", "few anionic antimicrobial peptides have", "anionic antimicrobial peptides have been", "antimicrobial peptides have been found", "peptides have been found in", "have been found in humans", "found in humans however", "in humans however their", "humans however their mechanism", "however their mechanism of action", "their mechanism of action remains", "mechanism of action remains to", "of action remains to be", "action remains to be clarified", "to be clarified lai", "be clarified lai y", "clarified lai y et", "lai y et al. 2007", "et al. 2007 harris", "al. 2007 harris f", "2007 harris f et", "harris f et al. 2009", "et al. 2009 paulmann", "al. 2009 paulmann m", "2009 paulmann m et", "paulmann m et al. 2012", "m et al. 2012 .", "et al. 2012 . besides", "al. 2012 . besides the", "2012 . besides the direct", ". besides the direct neutralizing", "besides the direct neutralizing effects", "the direct neutralizing effects on", "direct neutralizing effects on bacteria", "neutralizing effects on bacteria amps", "effects on bacteria amps may", "on bacteria amps may modulate", "bacteria amps may modulate cells", "amps may modulate cells of", "may modulate cells of the", "modulate cells of the adaptive", "cells of the adaptive immunity", "the adaptive immunity neutrophils", "immunity neutrophils t", "cells macrophages to", "macrophages to control inflammation", "to control inflammation and/or to", "control inflammation and/or to increase", "inflammation and/or to increase bacterial", "and/or to increase bacterial clearance.

              amps", "to increase bacterial clearance.

              amps have", "increase bacterial clearance.

              amps have also", "bacterial clearance.

              amps have also been", "clearance.

              amps have also been referred", "have also been referred to", "also been referred to as", "been referred to as cationic", "referred to as cationic host", "to as cationic host defense", "as cationic host defense peptides", "host defense peptides anionic", "defense peptides anionic antimicrobial", "peptides anionic antimicrobial peptides/proteins", "anionic antimicrobial peptides/proteins cationic", "antimicrobial peptides/proteins cationic amphipathic", "peptides/proteins cationic amphipathic peptides", "cationic amphipathic peptides cationic", "amphipathic peptides cationic amps", "cationic amps host defense", "amps host defense peptides", "host defense peptides and alpha", "defense peptides and alpha helical", "peptides and alpha helical antimicrobial", "and alpha helical antimicrobial peptides", "helical antimicrobial peptides brown", "antimicrobial peptides brown kl", "peptides brown kl &", "hancock re 2006 harris", "re 2006 harris f", "2006 harris f et", "et al. 2009 groenink", "al. 2009 groenink j", "2009 groenink j et", "groenink j et al. 1999", "et al. 1999 bradshaw", "al. 1999 bradshaw j", "1999 bradshaw j 2003", "bradshaw j 2003 riedl", "j 2003 riedl s", "2003 riedl s et", "riedl s et al. 2011", "et al. 2011 huang", "al. 2011 huang y", "2011 huang y et", "huang y et al. 2010", "y et al. 2010 .

              the", "et al. 2010 .

              the reactome", "al. 2010 .

              the reactome module", "2010 .

              the reactome module describes", ".

              the reactome module describes the", "reactome module describes the interaction", "module describes the interaction events", "describes the interaction events of", "the interaction events of various", "interaction events of various types", "events of various types of", "of various types of human", "various types of human amps", "of human amps such", "human amps such as", "amps such as cathelicidin", "such as cathelicidin histatins", "as cathelicidin histatins and", "cathelicidin histatins and neutrophil", "histatins and neutrophil serine proteases", "neutrophil serine proteases with", "serine proteases with conserved", "proteases with conserved patterns", "with conserved patterns of microbial", "conserved patterns of microbial membranes", "patterns of microbial membranes at", "of microbial membranes at the", "microbial membranes at the host", "membranes at the host pathogen", "at the host pathogen interface.", "the host pathogen interface. the", "host pathogen interface. the module", "pathogen interface. the module includes", "interface. the module includes also", "the module includes also proteolytic", "module includes also proteolytic processing", "includes also proteolytic processing events", "also proteolytic processing events for", "proteolytic processing events for dermcidin", "events for dermcidin dcd", "dermcidin dcd and", "cathelicidin camp that", "camp that become functional", "that become functional upon cleavage.", "become functional upon cleavage. in", "functional upon cleavage. in addition", "cleavage. in addition the", "in addition the module", "addition the module highlights", "the module highlights an amp", "module highlights an amp associated", "highlights an amp associated ability", "an amp associated ability of", "amp associated ability of the", "associated ability of the host", "ability of the host to", "of the host to control", "the host to control metal", "host to control metal quota", "to control metal quota at", "control metal quota at inflammation", "metal quota at inflammation sites", "quota at inflammation sites to", "at inflammation sites to influence", "inflammation sites to influence host", "sites to influence host pathogen", "to influence host pathogen interactions." ] }, { "record_id": "GLY_000594_1_1093", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6803529", "r hsa", "hsa 6803529", "r hsa 6803529" ] }, { "record_id": "GLY_000594_1_1093", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fgfr2 alternative", "alternative splicing", "fgfr2 alternative splicing", "splicing of", "of the", "the fgfr2", "fgfr2 nascent", "nascent mrna", "mrna generates", "generates an", "an epithelial", "epithelial specific", "specific isoform", "fgfr2 iiib", "and a", "a mesenchymal", "mesenchymal specific", "fgfr2 iiic", "iiic .", "the inclusion", "inclusion of", "of exon", "exon 8", "8 in", "in fgfr2", "iiib or", "or exon", "exon 9", "9 in", "iiic alters", "alters the", "the c", "c terminal", "terminal half", "half of", "the d3", "d3 loop", "loop of", "the receptor", "receptor and", "and is", "is responsible", "responsible for", "for the", "the different", "different ligand", "ligand binding", "binding specificities", "specificities of", "the two", "two isoforms", "reviewed in", "in eswarakumar", "eswarakumar et", "et al", "2005 .", "in recent", "recent years", "a number", "number of", "of cis", "and trans", "trans acting", "acting elements", "elements have", "have been", "been identified", "identified that", "that regulate", "regulate the", "the alternative", "splicing event.", "event. exon", "exon iiib", "iiib repression", "repression is", "is mediated", "mediated by", "by the", "the presence", "presence of", "of weak", "weak splice", "splice sites", "sites flanking", "flanking the", "the exon", "an exonic", "exonic silencing", "silencing sequence", "within the", "the iiib", "iiib exon", "exon and", "and both", "both intronic", "intronic silencing", "silencing sequences", "upstream and", "and downstream", "carstens et", "del gatto", "gatto and", "and breathnach", "gatto et", "wagner et", "al 2005", "wagner and", "and garcia", "garcia blanco", "2001 .", "binding of", "of hnrnpa1", "sr family", "family proteins", "proteins and", "and other", "other factors", "factors to", "to these", "these elements", "elements represses", "represses the", "and promotes", "promotes fgfr2", "iiic expression", "expression in", "in mesenchymal", "mesenchymal cells", "gatto konczak", "konczak et", "2002 .", "in epithelial", "epithelial cells", "recruitment of", "of epithelial", "specific factors", "factors shifts", "shifts the", "the splicing", "splicing events", "events to", "to favour", "favour inclusion", "exon 8.", "espn1 and", "and espn2", "espn2 are", "are epithelial", "factors that", "that bind", "bind to", "to an", "an ise/iss", "ise/iss 3", "intronic splicing", "splicing enhancer/intronic", "enhancer/intronic splicing", "splicing silencer", "silencer 3", "region within", "within intron", "intron 8", "8 to", "to promote", "promote fgfr2", "iiib specific", "specific splicing", "warzecha et", "2009 .", ". a", "a complex", "complex of", "of rbfox2", "hnrnph1 and", "and hnrnpf", "hnrnpf also", "also contribute", "contribute to", "to epithelial", "splicing by", "by competing", "competing for", "for binding", "binding to", "to a", "a site", "site that", "that is", "is occupied", "occupied by", "the sr", "sr proteins", "proteins asf/sf2", "asf/sf2 in", "baraniak et", "mauger et", "2008 .", "other proteins", "and sequences", "sequences have", "have also", "also been", "that appear", "appear to", "to contribute", "to the", "the regulated", "regulated expression", "expression of", "of fgfr2b", "fgfr2b and", "and fgfr2c", "but the", "the full", "full details", "details of", "splicing event", "event remain", "remain to", "to be", "be worked", "worked out", "muh et", "newman et", "hovhannisyan and", "and carstens", "2007 .", "alternative splicing of", "splicing of the", "of the fgfr2", "the fgfr2 nascent", "fgfr2 nascent mrna", "nascent mrna generates", "mrna generates an", "generates an epithelial", "an epithelial specific", "epithelial specific isoform", "isoform fgfr2", "iiib and", "and a mesenchymal", "a mesenchymal specific", "mesenchymal specific isoform", "fgfr2 iiic .", ". the", "the inclusion of", "inclusion of exon", "of exon 8", "exon 8 in", "8 in fgfr2", "in fgfr2 iiib", "fgfr2 iiib or", "iiib or exon", "or exon 9", "exon 9 in", "9 in fgfr2", "in fgfr2 iiic", "fgfr2 iiic alters", "iiic alters the", "alters the c", "the c terminal", "c terminal half", "terminal half of", "half of the", "of the d3", "the d3 loop", "d3 loop of", "loop of the", "of the receptor", "the receptor and", "receptor and is", "and is responsible", "is responsible for", "responsible for the", "for the different", "the different ligand", "different ligand binding", "ligand binding specificities", "binding specificities of", "specificities of the", "of the two", "the two isoforms", "isoforms reviewed", "reviewed in eswarakumar", "in eswarakumar et", "eswarakumar et al", ". in", "in recent years", "years a", "a number of", "number of cis", "cis and", "and trans acting", "trans acting elements", "acting elements have", "elements have been", "have been identified", "been identified that", "identified that regulate", "that regulate the", "regulate the alternative", "the alternative splicing", "alternative splicing event.", "splicing event. exon", "event. exon iiib", "exon iiib repression", "iiib repression is", "repression is mediated", "is mediated by", "mediated by the", "by the presence", "the presence of", "presence of weak", "of weak splice", "weak splice sites", "splice sites flanking", "sites flanking the", "flanking the exon", "exon an", "an exonic silencing", "exonic silencing sequence", "sequence ess", "ess within", "within the iiib", "the iiib exon", "iiib exon and", "exon and both", "and both intronic", "both intronic silencing", "intronic silencing sequences", "sequences iss", "iss upstream", "upstream and downstream", "downstream carstens", "carstens et al", "al 2000", "2000 del", "del gatto and", "gatto and breathnach", "breathnach 1995", "1995 del", "del gatto et", "gatto et al", "al 1996", "1996 wagner", "wagner et al", "et al 2005", "2005 wagner", "wagner and garcia", "and garcia blanco", "blanco 2001", ". binding", "binding of hnrnpa1", "hnrnpa1 ptb1", "ptb1 sr", "sr family proteins", "family proteins and", "proteins and other", "and other factors", "other factors to", "factors to these", "to these elements", "these elements represses", "elements represses the", "represses the iiib", "exon and promotes", "and promotes fgfr2", "promotes fgfr2 iiic", "fgfr2 iiic expression", "iiic expression in", "expression in mesenchymal", "in mesenchymal cells", "cells del", "del gatto konczak", "gatto konczak et", "konczak et al", "al 1999", "1999 carstens", "2000 wagner", "2001 wagner", "blanco 2002", "in epithelial cells", "cells recruitment", "recruitment of epithelial", "of epithelial specific", "epithelial specific factors", "specific factors shifts", "factors shifts the", "shifts the splicing", "the splicing events", "splicing events to", "events to favour", "to favour inclusion", "favour inclusion of", "of exon 8.", "8. espn1", "espn1 and espn2", "and espn2 are", "espn2 are epithelial", "are epithelial specific", "specific factors that", "factors that bind", "that bind to", "bind to an", "to an ise/iss", "an ise/iss 3", "3 intronic", "intronic splicing enhancer/intronic", "splicing enhancer/intronic splicing", "enhancer/intronic splicing silencer", "splicing silencer 3", "3 region", "region within intron", "within intron 8", "intron 8 to", "8 to promote", "to promote fgfr2", "promote fgfr2 iiib", "fgfr2 iiib specific", "iiib specific splicing", "splicing warzecha", "warzecha et al", "al 2009", "2009 . a", ". a complex", "a complex of", "complex of rbfox2", "rbfox2 hnrnph1", "hnrnph1 and hnrnpf", "and hnrnpf also", "hnrnpf also contribute", "also contribute to", "contribute to epithelial", "to epithelial specific", "epithelial specific splicing", "specific splicing by", "splicing by competing", "by competing for", "competing for binding", "for binding to", "binding to a", "to a site", "a site that", "site that is", "that is occupied", "is occupied by", "occupied by the", "by the sr", "the sr proteins", "sr proteins asf/sf2", "proteins asf/sf2 in", "asf/sf2 in mesenchymal", "cells baraniak", "baraniak et al", "al 2006", "2006 mauger", "mauger et al", "al 2008", ". other", "other proteins and", "proteins and sequences", "and sequences have", "sequences have also", "have also been", "also been identified", "identified that appear", "that appear to", "appear to contribute", "to contribute to", "contribute to the", "to the regulated", "the regulated expression", "regulated expression of", "expression of fgfr2b", "of fgfr2b and", "fgfr2b and fgfr2c", "fgfr2c but", "but the full", "the full details", "full details of", "details of the", "of the alternative", "alternative splicing event", "splicing event remain", "event remain to", "remain to be", "to be worked", "be worked out", "out muh", "muh et al", "al 2002", "2002 newman", "newman et al", "2006 del", "2000 hovhannisyan", "hovhannisyan and carstens", "carstens 2007", "alternative splicing of the", "splicing of the fgfr2", "of the fgfr2 nascent", "the fgfr2 nascent mrna", "fgfr2 nascent mrna generates", "nascent mrna generates an", "mrna generates an epithelial", "generates an epithelial specific", "an epithelial specific isoform", "specific isoform fgfr2", "isoform fgfr2 iiib", "fgfr2 iiib and", "iiib and a", "and a mesenchymal specific", "a mesenchymal specific isoform", "isoform fgfr2 iiic", "iiic . the", ". the inclusion", "the inclusion of exon", "inclusion of exon 8", "of exon 8 in", "exon 8 in fgfr2", "8 in fgfr2 iiib", "in fgfr2 iiib or", "fgfr2 iiib or exon", "iiib or exon 9", "or exon 9 in", "exon 9 in fgfr2", "9 in fgfr2 iiic", "in fgfr2 iiic alters", "fgfr2 iiic alters the", "iiic alters the c", "alters the c terminal", "the c terminal half", "c terminal half of", "terminal half of the", "half of the d3", "of the d3 loop", "the d3 loop of", "d3 loop of the", "loop of the receptor", "of the receptor and", "the receptor and is", "receptor and is responsible", "and is responsible for", "is responsible for the", "responsible for the different", "for the different ligand", "the different ligand binding", "different ligand binding specificities", "ligand binding specificities of", "binding specificities of the", "specificities of the two", "of the two isoforms", "two isoforms reviewed", "isoforms reviewed in", "reviewed in eswarakumar et", "in eswarakumar et al", "al 2005 .", "2005 . in", ". in recent", "recent years a", "years a number", "a number of cis", "of cis and", "cis and trans", "and trans acting elements", "trans acting elements have", "acting elements have been", "elements have been identified", "have been identified that", "been identified that regulate", "identified that regulate the", "that regulate the alternative", "regulate the alternative splicing", "the alternative splicing event.", "alternative splicing event. exon", "splicing event. exon iiib", "event. exon iiib repression", "exon iiib repression is", "iiib repression is mediated", "repression is mediated by", "is mediated by the", "mediated by the presence", "by the presence of", "the presence of weak", "presence of weak splice", "of weak splice sites", "weak splice sites flanking", "splice sites flanking the", "sites flanking the exon", "the exon an", "exon an exonic", "an exonic silencing sequence", "silencing sequence ess", "ess within the", "within the iiib exon", "the iiib exon and", "iiib exon and both", "exon and both intronic", "and both intronic silencing", "both intronic silencing sequences", "silencing sequences iss", "iss upstream and", "and downstream carstens", "downstream carstens et", "et al 2000", "2000 del gatto", "del gatto and breathnach", "and breathnach 1995", "1995 del gatto", "del gatto et al", "et al 1996", "1996 wagner et", "wagner et al 2005", "al 2005 wagner", "2005 wagner and", "wagner and garcia blanco", "garcia blanco 2001", "blanco 2001 .", "2001 . binding", ". binding of", "of hnrnpa1 ptb1", "ptb1 sr family", "sr family proteins and", "family proteins and other", "proteins and other factors", "and other factors to", "other factors to these", "factors to these elements", "to these elements represses", "these elements represses the", "elements represses the iiib", "represses the iiib exon", "iiib exon and promotes", "exon and promotes fgfr2", "and promotes fgfr2 iiic", "promotes fgfr2 iiic expression", "fgfr2 iiic expression in", "iiic expression in mesenchymal", "expression in mesenchymal cells", "mesenchymal cells del", "cells del gatto", "del gatto konczak et", "gatto konczak et al", "et al 1999", "1999 carstens et", "2000 wagner et", "2001 wagner and", "garcia blanco 2002", "blanco 2002 .", "2002 . in", ". in epithelial", "epithelial cells recruitment", "cells recruitment of", "recruitment of epithelial specific", "of epithelial specific factors", "epithelial specific factors shifts", "specific factors shifts the", "factors shifts the splicing", "shifts the splicing events", "the splicing events to", "splicing events to favour", "events to favour inclusion", "to favour inclusion of", "favour inclusion of exon", "inclusion of exon 8.", "exon 8. espn1", "8. espn1 and", "espn1 and espn2 are", "and espn2 are epithelial", "espn2 are epithelial specific", "are epithelial specific factors", "epithelial specific factors that", "specific factors that bind", "factors that bind to", "that bind to an", "bind to an ise/iss", "to an ise/iss 3", "ise/iss 3 intronic", "3 intronic splicing", "intronic splicing enhancer/intronic 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event", "alternative splicing event remain", "splicing event remain to", "event remain to be", "remain to be worked", "to be worked out", "worked out muh", "out muh et", "et al 2002", "2002 newman et", "2006 del gatto", "2000 hovhannisyan and", "and carstens 2007", "carstens 2007 .", "alternative splicing of the fgfr2", "splicing of the fgfr2 nascent", "of the fgfr2 nascent mrna", "the fgfr2 nascent mrna generates", "fgfr2 nascent mrna generates an", "nascent mrna generates an epithelial", "mrna generates an epithelial specific", "generates an epithelial specific isoform", "epithelial specific isoform fgfr2", "specific isoform fgfr2 iiib", "fgfr2 iiib and a", "iiib and a mesenchymal", "and a mesenchymal specific isoform", "mesenchymal specific isoform fgfr2", "specific isoform fgfr2 iiic", "isoform fgfr2 iiic .", "fgfr2 iiic . the", "iiic . the inclusion", ". the inclusion of", "the inclusion of exon 8", "inclusion of exon 8 in", "of exon 8 in fgfr2", "exon 8 in fgfr2 iiib", "8 in 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"presence of weak splice sites", "of weak splice sites flanking", "weak splice sites flanking the", "splice sites flanking the exon", "flanking the exon an", "the exon an exonic", "exon an exonic silencing", "exonic silencing sequence ess", "sequence ess within", "ess within the iiib", "within the iiib exon and", "the iiib exon and both", "iiib exon and both intronic", "exon and both intronic silencing", "and both intronic silencing sequences", "intronic silencing sequences iss", "sequences iss upstream", "iss upstream and downstream", "upstream and downstream carstens", "and downstream carstens et", "downstream carstens et al", "carstens et al 2000", "al 2000 del", "2000 del gatto and", "gatto and breathnach 1995", "breathnach 1995 del", "1995 del gatto et", "gatto et al 1996", "al 1996 wagner", "1996 wagner et al", "et al 2005 wagner", "al 2005 wagner and", "2005 wagner and garcia", "and garcia blanco 2001", "garcia blanco 2001 .", "2001 . binding of", ". binding of hnrnpa1", 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2010 .", "al. 2010 . the", "2010 . the histone", ". the histone acetyltransferase", "the histone acetyltransferase kat6a", "acetyltransferase kat6a in", "kat6a in the", "in the presence of", "the presence of pml", "of pml also", "pml also acetylates", "also acetylates tp53 at", "acetylates tp53 at k382", "at k382 and", "and in addition", "in addition acetylates", "addition acetylates k120", "acetylates k120 of tp53.", "k120 of tp53. kat6a", "of tp53. kat6a mediated", "tp53. kat6a mediated acetylation", "kat6a mediated acetylation increases", "mediated acetylation increases transcriptional", "acetylation increases transcriptional activation", "increases transcriptional activation of", "transcriptional activation of cdkn1a", "activation of cdkn1a by", "of cdkn1a by tp53", "by tp53 rokudai", "tp53 rokudai et", "rokudai et al. 2013", "et al. 2013 .", "al. 2013 . acetylation", "2013 . acetylation of", "acetylation of k382 can", "of k382 can be", "k382 can be reversed", "can be reversed by", "be reversed by the", "reversed by the action", "by the action of", "the action of the", "action of the nurd", "of the nurd complex", "nurd complex containing", "complex containing the", "containing the tp53 binding", "the tp53 binding mta2", "tp53 binding mta2 subunit", "mta2 subunit resulting", "subunit resulting in", "resulting in inhibition of", "in inhibition of tp53", "inhibition of tp53 transcriptional", "of tp53 transcriptional activity", "transcriptional activity luo", "activity luo et", "luo et al. 2000", "et al. 2000 .", "al. 2000 . acetylation", "2000 . acetylation of", ". acetylation of lysine", "acetylation of lysine k120", "of lysine k120 in", "lysine k120 in the", "k120 in the dna", "in the dna binding", "the dna binding domain", "dna binding domain of", "binding domain of tp53", "domain of tp53 by", "of tp53 by the", "tp53 by the myst", "by the myst family", "the myst family acetyltransferases", "myst family acetyltransferases kat8", "acetyltransferases kat8 hmof", "hmof and kat5", "and kat5 tip60", "tip60 can modulate", "can modulate the decision", "modulate the decision between", "the decision between cell", "decision between cell cycle", "between cell cycle arrest", "cell cycle arrest and", "cycle arrest and apoptosis", "and apoptosis sykes", "apoptosis sykes et", "sykes et al. 2006", "al. 2006 tang", "2006 tang et", "tang et al. 2006", "et al. 2006 .", "al. 2006 . studies", "2006 . studies with", ". studies with acetylation", "studies with acetylation defective", "with acetylation defective knock", "acetylation defective knock in", "defective knock in mutant", "knock in mutant mice", "in mutant mice indicate", "mutant mice indicate that", "mice indicate that lysine", "indicate that lysine acetylation", "that lysine acetylation in", "lysine acetylation in the", "acetylation in the p53", "in the p53 dna", "the p53 dna binding", "p53 dna binding domain", "dna binding domain acts", "binding domain acts in", "domain acts in part", "acts in part by", "in part by uncoupling", "part by uncoupling transactivation", "by uncoupling transactivation and", "uncoupling transactivation and transrepression", "transactivation and transrepression of", "and transrepression of gene", "transrepression of gene targets", "gene targets while", "targets while retaining", "while retaining ability to", "retaining ability to modulate", "ability to modulate energy", "to modulate energy metabolism", "modulate energy metabolism and", "energy metabolism and production", "metabolism and production of", "and production of reactive", "production of reactive oxygen", "of reactive oxygen species", "oxygen species ros", "ros and influencing", "influencing ferroptosis li", "ferroptosis li et", "li et al. 2012", "al. 2012 jiang", "2012 jiang et", "jiang et al. 2015", "et al. 2015 .", "transcriptional activity of tp53 is", "activity of tp53 is positively", "of tp53 is positively regulated", "tp53 is positively regulated by", "is positively regulated by acetylation", "positively regulated by acetylation of", "regulated by acetylation of several", "by acetylation of several of", "acetylation of several of its", "of several of its lysine", "several of its lysine residues.", "of its lysine residues. brd7", "its lysine residues. brd7 binds", "lysine residues. brd7 binds tp53", "residues. brd7 binds tp53 and", "brd7 binds tp53 and promotes", "binds tp53 and promotes acetylation", "tp53 and promotes acetylation of", "and promotes acetylation of tp53", "promotes acetylation of tp53 lysine", "acetylation of tp53 lysine residue", "of tp53 lysine residue k382", "tp53 lysine residue k382 by", "lysine residue k382 by acetyltransferase", "residue k382 by acetyltransferase ep300", "by acetyltransferase ep300 p300", "acetyltransferase ep300 p300 .", "ep300 p300 . acetylation", "p300 . acetylation of k382", ". acetylation of k382 enhances", "acetylation of k382 enhances tp53", "of k382 enhances tp53 binding", "k382 enhances tp53 binding to", "enhances tp53 binding to target", "tp53 binding to target promoters", "to target promoters including", "target promoters including cdkn1a", "mdm2 serpine1 tigar", "serpine1 tigar tnfrsf10c", "tigar tnfrsf10c and ndrg1", "tnfrsf10c and ndrg1 bensaad", "and ndrg1 bensaad et", "ndrg1 bensaad et al.", "et al. 2010 burrows", "al. 2010 burrows et", "2010 burrows et al.", "burrows et al. 2010. drost", "et al. 2010. drost et", "al. 2010. drost et al.", "2010. drost et al. 2010", "drost et al. 2010 .", "et al. 2010 . the", "al. 2010 . the histone", "2010 . the histone acetyltransferase", ". the histone acetyltransferase kat6a", "histone acetyltransferase kat6a in", "acetyltransferase kat6a in the", "kat6a in the presence", "in the presence of pml", "presence of pml also", "of pml also acetylates", "pml also acetylates tp53", "also acetylates tp53 at k382", "tp53 at k382 and", "k382 and in", "in addition acetylates k120", "addition acetylates k120 of", "acetylates k120 of tp53. kat6a", "k120 of tp53. kat6a mediated", "of tp53. kat6a mediated acetylation", "tp53. kat6a mediated acetylation increases", "kat6a mediated acetylation increases transcriptional", "mediated acetylation increases transcriptional activation", "acetylation increases transcriptional activation of", "increases transcriptional activation of cdkn1a", "transcriptional activation of cdkn1a by", "activation of cdkn1a by tp53", "cdkn1a by tp53 rokudai", "by tp53 rokudai et", "tp53 rokudai et al.", "rokudai et al. 2013 .", "et al. 2013 . acetylation", "al. 2013 . acetylation of", "2013 . acetylation of k382", ". acetylation of k382 can", "acetylation of k382 can be", "of k382 can be reversed", "k382 can be reversed by", "can be reversed by the", "be reversed by the action", "reversed by the action of", "by the action of the", "the action of the nurd", "action of the nurd complex", "the nurd complex containing", "nurd complex containing the", "complex containing the tp53", "containing the tp53 binding mta2", "the tp53 binding mta2 subunit", "binding mta2 subunit resulting", "mta2 subunit resulting in", "subunit resulting in inhibition", "resulting in inhibition of tp53", "in inhibition of tp53 transcriptional", "inhibition of tp53 transcriptional activity", "tp53 transcriptional activity luo", "transcriptional activity luo et", "activity luo et al.", "luo et al. 2000 .", "et al. 2000 . acetylation", "al. 2000 . acetylation of", "2000 . acetylation of lysine", ". acetylation of lysine k120", "acetylation of lysine k120 in", "of lysine k120 in the", "lysine k120 in the dna", "k120 in the dna binding", "in the dna binding domain", "the dna binding domain of", "dna binding domain of tp53", "binding domain of tp53 by", "domain of tp53 by the", "of tp53 by the myst", "tp53 by the myst family", "by the myst family acetyltransferases", "the myst family acetyltransferases kat8", "family acetyltransferases kat8 hmof", "kat8 hmof and", "kat5 tip60 can", "tip60 can modulate the", "can modulate the decision between", "modulate the decision between cell", "the decision between cell cycle", "decision between cell cycle arrest", "between cell cycle arrest and", "cell cycle arrest and apoptosis", "arrest and apoptosis sykes", "and apoptosis sykes et", "apoptosis sykes et al.", "et al. 2006 tang", "al. 2006 tang et", "2006 tang et al.", "tang et al. 2006 .", "et al. 2006 . studies", "al. 2006 . studies with", "2006 . studies with acetylation", ". studies with acetylation defective", "studies with acetylation defective knock", "with acetylation defective knock in", "acetylation defective knock in mutant", "defective knock in mutant mice", "knock in mutant mice indicate", "in mutant mice indicate that", "mutant mice indicate that lysine", "mice indicate that lysine acetylation", "indicate that lysine acetylation in", "that lysine acetylation in the", "lysine acetylation in the p53", "acetylation in the p53 dna", "in the p53 dna binding", "the p53 dna binding domain", "p53 dna binding domain acts", "dna binding domain acts in", "binding domain acts in part", "domain acts in part by", "acts in part by uncoupling", "in part by uncoupling transactivation", "part by uncoupling transactivation and", "by uncoupling transactivation and transrepression", "uncoupling transactivation and transrepression of", "transactivation and transrepression of gene", "and transrepression of gene targets", "of gene targets while", "gene targets while retaining", "targets while retaining ability", "while retaining ability to modulate", "retaining ability to modulate energy", "ability to modulate energy metabolism", "to modulate energy metabolism and", "modulate energy metabolism and production", "energy metabolism and production of", "metabolism and production of reactive", "and production of reactive oxygen", "production of reactive oxygen species", "reactive oxygen species ros", "species ros and", "ros and influencing ferroptosis", "and influencing ferroptosis li", "influencing ferroptosis li et", "ferroptosis li et al.", "et al. 2012 jiang", "al. 2012 jiang et", "2012 jiang et al.", "jiang et al. 2015 ." ] }, { "record_id": "GLY_000594_1_1096", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6806942", "r hsa", "hsa 6806942", "r hsa 6806942" ] }, { "record_id": "GLY_000594_1_1096", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "met receptor", "receptor activation", "met receptor activation", "hepatocyte growth", "growth factor", "the ligand", "ligand for", "for met", "receptor tyrosine", "tyrosine kinase", "is secreted", "secreted into", "into the", "the extracellular", "extracellular matrix", "as an", "an inactive", "inactive single", "single chain", "chain precursor", "pro hgf", "hgf .", ". the", "the biologically", "biologically active", "active hgf", "hgf is", "is the", "the heterodimer", "heterodimer of", "of alpha", "alpha and", "and beta", "beta chains", "chains that", "that 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              cd44v6", ".
              cd44v6 was", "was implicated", "implicated as", "as a", "a met", "met co", "co receptor", "but its", "its role", "role has", "has been", "been disputed", "orian rousseau", "rousseau et", "al. 2002", "dortet et", "olaku et", "al. 2011", "hasenauer et", "al. 2013", "elliot et", "al. 2014", "2014 .", "hepatocyte growth factor", "factor hgf", "the ligand for", "ligand for met", "for met receptor", "met receptor tyrosine", "receptor tyrosine kinase", "kinase rtk", "is secreted into", "secreted into the", "into the extracellular", "the extracellular matrix", "matrix ecm", "ecm as", "as an inactive", "an inactive single", "inactive single chain", "single chain precursor", "precursor pro", "pro hgf .", "hgf . the", ". the biologically", "the biologically active", "biologically active hgf", "active hgf is", "hgf is the", "is the heterodimer", "the heterodimer of", "heterodimer of alpha", "of alpha and", "alpha and beta", "and beta chains", "beta chains that", "chains that are", "that are produced", "are produced via", "produced via proteolytic", "via proteolytic cleavage", "proteolytic cleavage of", "cleavage of pro", "of pro hgf", "pro hgf by", "hgf by the", "by the plasma", "the plasma membrane", "plasma membrane bound", "membrane bound serine", "bound serine protease", "serine protease hepsin", "hepsin hpn", "kirchhofer et al.", "et al. 2005", "2005 owen", "owen et al.", "et al. 2010", "2010 or", "or the ecm", "the ecm associated", "ecm associated serine", "associated serine protease", "serine protease hepatocyte", "protease hepatocyte growth", "growth factor activator", "activator hgfac", "hgfac commonly", "commonly known as", "known as hgfa", "shia et al.", "al. 2005 .", "2005 . hgf", ". hgf binds", "hgf binds to", "binds to the", "to the extracellular", "the extracellular sema", "extracellular sema and", "sema and psi", "and psi domains", "psi domains of", "domains of met", "of met rtk", "rtk inducing", "inducing a conformational", "a conformational change", "conformational change that", "change that enables", "that enables met", "enables met dimerization", "met dimerization or", "dimerization or oligomerization", "oligomerization kirchhofer", "et al. 2004", "2004 stamos", "stamos et al.", "2004 hays", "hays and watowich", "and watowich 2004", "2004 gherardi", "gherardi et al.", "et al. 2006", "al. 2006 .", "2006 . met", ". met dimers", "met dimers trans", "dimers trans autophosphorylate", "trans autophosphorylate on", "autophosphorylate on tyrosine", "on tyrosine residues", "tyrosine residues in", "residues in the", "in the activation", "the activation loop", "loop leading", "leading to increased", "to increased kinase", "increased kinase activity", "activity and", "and on tyrosine", "tyrosine residues at", "residues at the", "at the cytoplasmic", "the cytoplasmic tail", "cytoplasmic tail that", "tail that serve", "that serve as", "serve as docking", "as docking sites", "docking sites for", "sites for adapter", "for adapter proteins", "adapter proteins involved", "proteins involved in", "involved in met", "in met signal", "met signal transduction", "transduction ferracini", "ferracini et al.", "et al. 1991", "1991 longati", "longati et al.", "et al. 1994", "1994 rodrigues", "rodrigues and park", "and park 1994", "1994 ponzetto", "ponzetto et al.", "al. 1994 .
              cd44v6", "1994 .
              cd44v6 was", ".
              cd44v6 was implicated", "was implicated as", "implicated as a", "as a met", "a met co", "met co receptor", "receptor but", "but its role", "its role has", "role has been", "has been disputed", "disputed orian", "orian rousseau et", "rousseau et al.", "et al. 2002", "2002 dortet", "dortet et al.", "2010 olaku", "olaku et al.", "et al. 2011", "2011 hasenauer", "hasenauer et al.", "et al. 2013", "2013 elliot", "elliot et al.", "et al. 2014", "al. 2014 .", "growth factor hgf", "hgf the", "the ligand for met", "ligand for met receptor", "for met receptor tyrosine", "met receptor tyrosine kinase", "tyrosine kinase rtk", "rtk is", "is secreted into the", "secreted into the extracellular", "into the extracellular matrix", "extracellular matrix ecm", "ecm as an", "as an inactive single", "an inactive single chain", "inactive single chain precursor", "chain precursor pro", "precursor pro hgf", "pro hgf . the", "hgf . the biologically", ". the biologically active", "the biologically active hgf", "biologically active hgf is", "active hgf is the", "hgf is the heterodimer", "is the heterodimer of", "the heterodimer of alpha", "heterodimer of alpha and", "of alpha and beta", "alpha and beta chains", "and beta chains that", "beta chains that are", "chains that are produced", "that are produced via", "are produced via proteolytic", "produced via proteolytic cleavage", "via proteolytic cleavage of", "proteolytic cleavage of pro", "cleavage of pro hgf", "of pro hgf by", "pro hgf by the", "hgf by the plasma", "by the plasma membrane", "the plasma membrane bound", "plasma membrane bound serine", "membrane bound serine protease", "bound serine protease hepsin", "protease hepsin hpn", "hpn kirchhofer", "kirchhofer et al. 2005", "al. 2005 owen", "2005 owen et", "owen et al. 2010", "al. 2010 or", "2010 or the", "or the ecm associated", "the ecm associated serine", "ecm associated serine protease", "associated serine protease hepatocyte", "serine protease hepatocyte growth", "protease hepatocyte growth factor", "hepatocyte growth factor activator", "factor activator hgfac", "hgfac commonly known", "commonly known as hgfa", "hgfa shia", "shia et al. 2005", "et al. 2005 .", "al. 2005 . hgf", "2005 . hgf binds", ". hgf binds to", "hgf binds to the", "binds to the extracellular", "to the extracellular sema", "the extracellular sema and", "extracellular sema and psi", "sema and psi domains", "and psi domains of", "psi domains of met", "domains of met rtk", "met rtk inducing", "rtk inducing a", "inducing a conformational change", "a conformational change that", "conformational change that enables", "change that enables met", "that enables met dimerization", "enables met dimerization or", "met dimerization or oligomerization", "or oligomerization kirchhofer", "oligomerization kirchhofer et", "kirchhofer et al. 2004", "al. 2004 stamos", "2004 stamos et", "stamos et al. 2004", "al. 2004 hays", "2004 hays and", "hays and watowich 2004", "watowich 2004 gherardi", "2004 gherardi et", "gherardi et al. 2006", "et al. 2006 .", "al. 2006 . met", "2006 . met dimers", ". met dimers trans", "met dimers trans autophosphorylate", "dimers trans autophosphorylate on", "trans autophosphorylate on tyrosine", "autophosphorylate on tyrosine residues", "on tyrosine residues in", "tyrosine residues in the", "residues in the activation", "in the activation loop", "activation loop leading", "loop leading to", "leading to increased kinase", "to increased kinase activity", "kinase activity and", "activity and on", "and on tyrosine residues", "on tyrosine residues at", "tyrosine residues at the", "residues at the cytoplasmic", "at the cytoplasmic tail", "the cytoplasmic tail that", "cytoplasmic tail that serve", "tail that serve as", "that serve as docking", "serve as docking sites", "as docking sites for", "docking sites for adapter", "sites for adapter proteins", "for adapter proteins involved", "adapter proteins involved in", "proteins involved in met", "involved in met signal", "in met signal transduction", "signal transduction ferracini", "transduction ferracini et", "ferracini et al. 1991", "al. 1991 longati", "1991 longati et", "longati et al. 1994", "al. 1994 rodrigues", "1994 rodrigues and", "rodrigues and park 1994", "park 1994 ponzetto", "1994 ponzetto et", "ponzetto et al. 1994", "et al. 1994 .
              cd44v6", "al. 1994 .
              cd44v6 was", "1994 .
              cd44v6 was implicated", ".
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precursor", "single chain precursor pro", "chain precursor pro hgf", "precursor pro hgf .", "pro hgf . the biologically", "hgf . the biologically active", ". the biologically active hgf", "the biologically active hgf is", "biologically active hgf is the", "active hgf is the heterodimer", "hgf is the heterodimer of", "is the heterodimer of alpha", "the heterodimer of alpha and", "heterodimer of alpha and beta", "of alpha and beta chains", "alpha and beta chains that", "and beta chains that are", "beta chains that are produced", "chains that are produced via", "that are produced via proteolytic", "are produced via proteolytic cleavage", "produced via proteolytic cleavage of", "via proteolytic cleavage of pro", "proteolytic cleavage of pro hgf", "cleavage of pro hgf by", "of pro hgf by the", "pro hgf by the plasma", "hgf by the plasma membrane", "by the plasma membrane bound", "the plasma membrane bound serine", "plasma membrane bound serine protease", "membrane bound serine protease hepsin", "serine protease hepsin hpn", "hpn kirchhofer et", "et al. 2005 owen", "al. 2005 owen et", "2005 owen et al.", "et al. 2010 or", "al. 2010 or the", "2010 or the ecm", "or the ecm associated serine", "the ecm associated serine protease", "ecm associated serine protease hepatocyte", "associated serine protease hepatocyte growth", "serine protease hepatocyte growth factor", "protease hepatocyte growth factor activator", "growth factor activator hgfac", "activator hgfac commonly", "hgfac commonly known as", "as hgfa shia", "hgfa shia et", "shia et al. 2005 .", "et al. 2005 . hgf", "al. 2005 . hgf binds", "2005 . hgf binds to", ". hgf binds to the", "hgf binds to the extracellular", "binds to the extracellular sema", "to the extracellular sema and", "the extracellular sema and psi", "extracellular sema and psi domains", "sema and psi domains of", "and psi domains of met", "psi domains of met rtk", "of met rtk inducing", "met rtk inducing a", "rtk inducing a conformational", "inducing a conformational change that", "a conformational change that enables", "conformational change that enables met", "change that enables met dimerization", "that enables met dimerization or", "enables met dimerization or oligomerization", "dimerization or oligomerization kirchhofer", "or oligomerization kirchhofer et", "oligomerization kirchhofer et al.", "et al. 2004 stamos", "al. 2004 stamos et", "2004 stamos et al.", "et al. 2004 hays", "al. 2004 hays and", "2004 hays and watowich", "and watowich 2004 gherardi", "watowich 2004 gherardi et", "2004 gherardi et al.", "gherardi et al. 2006 .", "et al. 2006 . met", "al. 2006 . met dimers", "2006 . met dimers trans", ". met dimers trans autophosphorylate", "met dimers trans autophosphorylate on", "dimers trans autophosphorylate on tyrosine", "trans autophosphorylate on tyrosine residues", "autophosphorylate on tyrosine residues in", "on tyrosine residues in the", "tyrosine residues in the activation", "residues in the activation loop", "the activation loop leading", "activation loop leading to", "loop leading to increased", "leading to increased kinase activity", "increased kinase activity and", "kinase activity and on", "activity and on tyrosine", "and on tyrosine residues at", "on tyrosine residues at the", "tyrosine residues at the cytoplasmic", "residues at the cytoplasmic tail", "at the cytoplasmic tail that", "the cytoplasmic tail that serve", "cytoplasmic tail that serve as", "tail that serve as docking", "that serve as docking sites", "serve as docking sites for", "as docking sites for adapter", "docking sites for adapter proteins", "sites for adapter proteins involved", "for adapter proteins involved in", "adapter proteins involved in met", "proteins involved in met signal", "involved in met signal transduction", "met signal transduction ferracini", "signal transduction ferracini et", "transduction ferracini et al.", "et al. 1991 longati", "al. 1991 longati et", "1991 longati et al.", "et al. 1994 rodrigues", "al. 1994 rodrigues and", "1994 rodrigues and park", "and park 1994 ponzetto", "park 1994 ponzetto et", "1994 ponzetto et al.", "ponzetto et al. 1994 .
              cd44v6", "et al. 1994 .
              cd44v6 was", "al. 1994 .
              cd44v6 was implicated", "1994 .
              cd44v6 was implicated as", ".
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              most", ".

              most human", "human replication", "origins contain", "contain guanine", "rich sequences", "sequences which", "which may", "may form", "form g", "g quadruplex", "besnard et", "al. 2012", "and these", "these g4", "g4 structures", "structures may", "may mediate", "mediate the", "the recognition", "recognition of", "origins by", "by orc1", ". besides", "besides binding", "binding to", "to nucleosome", "nucleosome free", "free replication", "replication origin", "origin dna", "orc1 interacts", "interacts with", "with neighboring", "neighboring nucleosomes", "hizume et", "in particular", "particular with", "with nucleosomes", "nucleosomes containing", "containing histone", "histone h4", "h4 dimethylated", "dimethylated at", "at lysine", "lysine 21", "h4k20me2 mark", "which is", "is enriched", "enriched at", "at replication", "replication origins.", "origins. binding", "binding of", "of orc1", "orc1 to", "to h4k20me2", "h4k20me2 facilitates", "facilitates orc1", "orc1 binding", "to replication", "origins and", "and orc", "orc chromatin", "chromatin loading", "kuo et", "zhang et", "2015 .

              orc1", ".

              orc1 binding", "binding sites", "sites are", "are universally", "universally associated", "with transcription", "transcription start", "start sites", "of coding", "coding and", "and non", "non coding", "coding rnas.", "rnas. replication", "origins associated", "with moderate", "moderate to", "to high", "high transcription", "transcription level", "level tsss", "belonging to", "to coding", "coding rnas", "fire in", "in early", "early s", "while those", "those associated", "with low", "low transcription", "to non", "fire throughout", "throughout the", "the s", "dellino et", "2013 .

              orc2", ".

              orc2 forms", "forms a", "a heterodimer", "heterodimer with", "with orc3", "is a", "a prerequisite", "prerequisite for", "the association", "association of", "of orc5", "orc5 and", "ranjan and", "and gossen", "gossen 2006", "siddiqui and", "and stillman", "stillman 2007", "2007 .", "orc1 binds", "binds to", "to the", "orc 2", "2 5", "complex in", "in the", "the nucleus", "nucleus to", "to form", "form a", "a stable", "stable orc", "orc 1", "1 5", "radichev et", "al. 2006", "ghosh et", "al. 2011", "2011 .", "orc1 is", "is necessary", "necessary for", "complex to", "to chromatin", "2006 .", ". the", "complex exhibits", "exhibits a", "a tightly", "tightly autoinhibited", "autoinhibited conformation", "with the", "the winged", "winged helix", "helix domain", "of orc2", "orc2 completely", "completely blocking", "blocking the", "the central", "central dna", "dna binding", "binding channel.", "channel. binding", "orc1 remodels", "remodels the", "the whd", "whd of", "moving it", "it away", "away from", "from the", "central channel", "channel and", "and partially", "partially relieving", "relieving the", "the autoinhibition", "cheng et", "al. 2020", "jaremko et", "2020 .", ". orc6", "orc6 associates", "associates with", "form the", "1 6", "of orc6", "orc6 with", "complex is", "is weak", "weak and", "and it", "it frequently", "frequently does", "does not", "not co", "co immunoprecipitate", "immunoprecipitate with", "the other", "other orc", "subunits. orc4", "orc4 is", "is the", "the only", "only orc", "subunit that", "that was", "was shown", "shown to", "to directly", "directly bind", "bind to", "to orc6", ". some", "some orc6", "orc6 mutations", "mutations reported", "reported in", "in meier", "meier gorlin", "gorlin syndrome", "syndrome were", "were shown", "to interfere", "interfere with", "with orc6", "orc6 incorporation", "incorporation into", "into the", "balasov et", "2015 .", "human orc1 can", "orc1 can associate", "can associate with", "associate with dna", "with dna origin", "dna origin of", "of replication sites", "replication sites independently", "sites independently of", "independently of other", "of other origin", "other origin of", "of replication complex", "complex orc", "orc subunits", "subunits hoshina", "hoshina et al.", "et al. 2013", "2013 eladl", "eladl et al.", "et al. 2021", "al. 2021 .", "2021 . orc1", ". orc1 localizes", "orc1 localizes to", "localizes to condensed", "to condensed chromosomes", "condensed chromosomes during", "chromosomes during early", "during early mitosis", "mitosis m", "phase and", "and serves as", "serves as a", "as a nucleating", "a nucleating center", "nucleating center for", "center for the", "for the assembly", "the assembly of", "the orc and", "and subsequently", "subsequently the", "the pre replication", "pre replication complex.", "replication complex. orc1", "complex. orc1 remains", "orc1 remains associated", "remains associated with", "associated with late", "with late replication", "late replication origins", "replication origins throughout", "origins throughout late", "throughout late g1.", "late g1. upon", "g1. upon s", "upon s phase", "s phase entry", "entry orc1", "orc1 undergoes ubiquitin", "undergoes ubiquitin mediated", "ubiquitin mediated degradation", "degradation leading", "leading to dissociation", "to dissociation of", "dissociation of the", "the orc from", "orc from chromatin", "chromatin kara", "kara et al.", "et al. 2015", "al. 2015 .

              most", "2015 .

              most human", ".

              most human replication", "human replication origins", "replication origins contain", "origins contain guanine", "guanine g", "g rich", "rich sequences which", "sequences which may", "which may form", "may form g", "form g quadruplex", "quadruplex g4", "structures besnard", "besnard et al.", "et al. 2012", "2012 and", "and these g4", "these g4 structures", "g4 structures may", "structures may mediate", "may mediate the", "mediate the recognition", "the recognition of", "recognition of replication", "of replication origins", "replication origins by", "origins by orc1", "orc1 hoshina", "2021 . besides", ". besides binding", "besides binding to", "binding to nucleosome", "to nucleosome free", "nucleosome free replication", "free replication origin", "replication origin dna", "dna orc1", "orc1 interacts with", "interacts with neighboring", "with neighboring nucleosomes", "nucleosomes hizume", "hizume et al.", "in particular with", "particular with nucleosomes", "with nucleosomes containing", "nucleosomes containing histone", "containing histone h4", "histone h4 dimethylated", "h4 dimethylated at", "dimethylated at lysine", "at lysine 21", "21 h4k20me2", "which is enriched", "is enriched at", "enriched at replication", "at replication origins.", "replication origins. binding", "origins. binding of", "binding of orc1", "of orc1 to", "orc1 to h4k20me2", "to h4k20me2 facilitates", "h4k20me2 facilitates orc1", "facilitates orc1 binding", "orc1 binding to", "binding to replication", "to replication origins", "replication origins and", "origins and orc", "and orc chromatin", "orc chromatin loading", "loading kuo", "kuo et al.", "2012 zhang", "zhang et al.", "al. 2015 .

              orc1", "2015 .

              orc1 binding", ".

              orc1 binding sites", "binding sites are", "sites are universally", "are universally associated", "universally associated with", "associated with transcription", "with transcription start", "transcription start sites", "sites tsss", "tsss of", "of coding and", "coding and non", "and non coding", "non coding rnas.", "coding rnas. replication", "rnas. replication origins", "replication origins associated", "origins associated with", "associated with moderate", "with moderate to", "moderate to high", "to high transcription", "high transcription level", "transcription level tsss", "tsss belonging", "belonging to coding", "to coding rnas", "rnas fire", "fire in early", "in early s", "early s phase", "phase while", "while those associated", "those associated with", "associated with low", "with low transcription", "low transcription level", "belonging to non", "to non coding", "non coding rnas", "fire throughout the", "throughout the s", "the s phase", "phase dellino", "dellino et al.", "al. 2013 .

              orc2", "2013 .

              orc2 forms", ".

              orc2 forms a", "forms a heterodimer", "a heterodimer with", "heterodimer with orc3", "orc3 which", "which is a", "is a prerequisite", "a prerequisite for", "prerequisite for the", "for the association", "the association of", "association of orc5", "of orc5 and", "subsequently orc4", "orc4 ranjan", "ranjan and gossen", "and gossen 2006", "2006 siddiqui", "siddiqui and stillman", "and stillman 2007", "stillman 2007 .", "2007 . orc1", ". orc1 binds", "orc1 binds to", "binds to the", "to the orc", "the orc 2", "orc 2 5", "5 complex", "complex in the", "in the nucleus", "the nucleus to", "nucleus to form", "to form a", "form a stable", "a stable orc", "stable orc 1", "orc 1 5", "complex radichev", "radichev et al.", "et al. 2006", "2006 ghosh", "ghosh et al.", "et al. 2011", "al. 2011 .", "2011 . orc1", ". orc1 is", "orc1 is necessary", "is necessary for", "necessary for the", "association of the", "complex to chromatin", "chromatin radichev", "al. 2006 .", "2006 . the", ". the orc", "complex exhibits a", "exhibits a tightly", "a tightly autoinhibited", "tightly autoinhibited conformation", "conformation with", "with the winged", "the winged helix", "winged helix domain", "domain whd", "of orc2 completely", "orc2 completely blocking", "completely blocking the", "blocking the central", "the central dna", "central dna binding", "dna binding channel.", "binding channel. binding", "channel. binding of", "of orc1 remodels", "orc1 remodels the", "remodels the whd", "the whd of", "whd of orc2", "orc2 moving", "moving it away", "it away from", "away from the", "from the central", "the central channel", "central channel and", "channel and partially", "and partially relieving", "partially relieving the", "relieving the autoinhibition", "autoinhibition cheng", "cheng et al.", "et al. 2020", "2020 jaremko", "jaremko et al.", "al. 2020 .", "2020 . orc6", ". orc6 associates", "orc6 associates with", "associates with the", "with the orc", "the orc 1", "complex to form", "to form the", "form the orc", "orc 1 6", "6 complex", "complex ghosh", "2011 . the", ". the association", "association of orc6", "of orc6 with", "orc6 with the", "complex is weak", "is weak and", "weak and it", "and it frequently", "it frequently does", "frequently does not", "does not co", "not co immunoprecipitate", "co immunoprecipitate with", "immunoprecipitate with the", "with the other", "the other orc", "other orc 1", "5 subunits.", "subunits. orc4 is", "orc4 is the", "is the only", "the only orc", "only orc 1", "5 subunit", "subunit that was", "that was shown", "was shown to", "shown to directly", "to directly bind", "directly bind to", "bind to orc6", "orc6 radichev", "2006 . some", ". some orc6", "some orc6 mutations", "orc6 mutations reported", "mutations reported in", "reported in meier", "in meier gorlin", "meier gorlin syndrome", "gorlin syndrome were", "syndrome were shown", "were shown to", "shown to interfere", "to interfere with", "interfere with orc6", "with orc6 incorporation", "orc6 incorporation into", "incorporation into the", "into the orc", "orc balasov", "balasov et al.", "al. 2015 .", "human orc1 can associate", "orc1 can associate with", "can associate with dna", "associate with dna origin", "with dna origin of", "dna origin of replication", "origin of replication sites", "of replication sites independently", "replication sites independently of", "sites independently of other", "independently of other origin", "of other origin of", "other origin of replication", "origin of replication complex", "replication complex orc", "subunits hoshina et", "hoshina et al. 2013", "al. 2013 eladl", "2013 eladl et", "eladl et al. 2021", "et al. 2021 .", "al. 2021 . orc1", "2021 . orc1 localizes", ". orc1 localizes to", "orc1 localizes to condensed", "localizes to condensed chromosomes", "to condensed chromosomes during", "condensed chromosomes during early", "chromosomes during early mitosis", "early mitosis m", "mitosis m phase", "m phase and", "phase and serves", "and serves as a", "serves as a nucleating", "as a nucleating center", "a nucleating center for", "nucleating center for the", "center for the assembly", "for the assembly of", "the assembly of the", "of the orc and", "orc and subsequently", "subsequently the pre", "the pre replication complex.", "pre replication complex. orc1", "replication complex. orc1 remains", "complex. orc1 remains associated", "orc1 remains associated with", "remains associated with late", "associated with late replication", "with late replication origins", "late replication origins throughout", "replication origins throughout late", "origins throughout late g1.", "throughout late g1. upon", "late g1. upon s", "g1. upon s phase", "upon s phase entry", "phase entry orc1", "entry orc1 undergoes", "orc1 undergoes ubiquitin mediated", "undergoes ubiquitin mediated degradation", "mediated degradation leading", "degradation leading to", "leading to dissociation of", "to dissociation of the", "dissociation of the orc", "of the orc from", "the orc from chromatin", "from chromatin kara", "chromatin kara et", "kara et al. 2015", "et al. 2015 .

              most", "al. 2015 .

              most human", "2015 .

              most human replication", ".

              most human replication origins", "human replication origins contain", "replication origins contain guanine", "contain guanine g", "g rich sequences", "rich sequences which may", "sequences which may form", "which may form g", "may form g quadruplex", "g quadruplex g4", "structures besnard et", "besnard et al. 2012", "al. 2012 and", "2012 and these", "and these g4 structures", "these g4 structures may", "g4 structures may mediate", "structures may mediate the", "may mediate the recognition", "mediate the recognition of", "the recognition of replication", "recognition of replication origins", "of replication origins by", "replication origins by orc1", "by orc1 hoshina", "orc1 hoshina et", "al. 2021 . besides", "2021 . besides binding", ". besides binding to", "besides binding to nucleosome", "binding to nucleosome free", "to nucleosome free replication", "nucleosome free replication origin", "free replication origin dna", "origin dna orc1", "dna orc1 interacts", "orc1 interacts with neighboring", "interacts with neighboring nucleosomes", "neighboring nucleosomes hizume", "nucleosomes hizume et", "hizume et al. 2013", "2013 in", "in particular with nucleosomes", "particular with nucleosomes containing", "with nucleosomes containing histone", "nucleosomes containing histone h4", "containing histone h4 dimethylated", "histone h4 dimethylated at", "h4 dimethylated at lysine", "dimethylated at lysine 21", "lysine 21 h4k20me2", "21 h4k20me2 mark", "mark which", "which is enriched at", "is enriched at replication", "enriched at replication origins.", "at replication origins. binding", "replication origins. binding of", "origins. binding of orc1", "binding of orc1 to", "of orc1 to h4k20me2", "orc1 to h4k20me2 facilitates", "to h4k20me2 facilitates orc1", "h4k20me2 facilitates orc1 binding", "facilitates orc1 binding to", "orc1 binding to replication", "binding to replication origins", "to replication origins and", "replication origins and orc", "origins and orc chromatin", "and orc chromatin loading", "chromatin loading kuo", "loading kuo et", "kuo et al. 2012", "al. 2012 zhang", "2012 zhang et", "zhang et al. 2015", "et al. 2015 .

              orc1", "al. 2015 .

              orc1 binding", "2015 .

              orc1 binding sites", ".

              orc1 binding sites are", "binding sites are universally", "sites are universally associated", "are universally associated with", "universally associated with transcription", "associated with transcription start", "with transcription start sites", "start sites tsss", "tsss of coding", "of coding and non", "coding and non coding", "and non coding rnas.", "non coding rnas. replication", "coding rnas. replication origins", "rnas. replication origins associated", "replication origins associated with", "origins associated with moderate", "associated with moderate to", "with moderate to high", "moderate to high transcription", "to high transcription level", "high transcription level tsss", "level tsss belonging", "tsss belonging to", "belonging to coding rnas", "coding rnas fire", "rnas fire in", "fire in early s", "in early s phase", "s phase while", "phase while those", "while those associated with", "those associated with low", "associated with low transcription", "with low transcription level", "low transcription level tsss", "belonging to non coding", "to non coding rnas", "rnas fire throughout", "fire throughout the s", "throughout the s phase", "s phase dellino", "phase dellino et", "dellino et al. 2013", "et al. 2013 .

              orc2", "al. 2013 .

              orc2 forms", "2013 .

              orc2 forms a", ".

              orc2 forms a heterodimer", "forms a heterodimer with", "a heterodimer with orc3", "with orc3 which", "orc3 which is", "which is a prerequisite", "is a prerequisite for", "a prerequisite for the", "prerequisite for the association", "for the association of", "the association of orc5", "association of orc5 and", "orc5 and subsequently", "orc4 ranjan and", "ranjan and gossen 2006", "gossen 2006 siddiqui", "2006 siddiqui and", "siddiqui and stillman 2007", "and stillman 2007 .", "stillman 2007 . orc1", "2007 . orc1 binds", ". orc1 binds to", "orc1 binds to the", "binds to the orc", "to the orc 2", "the orc 2 5", "2 5 complex", "5 complex in", "complex in the nucleus", "in the nucleus to", "the nucleus to form", "nucleus to form a", "to form a stable", "form a stable orc", "a stable orc 1", "stable orc 1 5", "1 5 complex", "complex radichev et", "radichev et al. 2006", "al. 2006 ghosh", "2006 ghosh et", "ghosh et al. 2011", "et al. 2011 .", "al. 2011 . orc1", "2011 . orc1 is", ". orc1 is necessary", "orc1 is necessary for", "is necessary for the", "necessary for the association", "the association of the", "association of the orc", "of the orc 2", "5 complex to", "to chromatin radichev", "chromatin radichev et", "et al. 2006 .", "al. 2006 . the", "2006 . the orc", ". the orc 2", "5 complex exhibits", "complex exhibits a tightly", "exhibits a tightly autoinhibited", "a tightly autoinhibited conformation", "autoinhibited conformation with", "conformation with the", "with the winged helix", "the winged helix domain", "helix domain whd", "of orc2 completely blocking", "orc2 completely blocking the", "completely blocking the central", "blocking the central dna", "the central dna binding", "central dna binding channel.", "dna binding channel. binding", "binding channel. binding of", "channel. binding of orc1", "binding of orc1 remodels", "of orc1 remodels the", "orc1 remodels the whd", "remodels the whd of", "the whd of orc2", "of orc2 moving", "orc2 moving it", "moving it away from", "it away from the", "away from the central", "from the central channel", "the central channel and", "central channel and partially", "channel and partially relieving", "and partially relieving the", "partially relieving the autoinhibition", "the autoinhibition cheng", "autoinhibition cheng et", "cheng et al. 2020", "al. 2020 jaremko", "2020 jaremko et", "jaremko et al. 2020", "et al. 2020 .", "al. 2020 . orc6", "2020 . orc6 associates", ". orc6 associates with", "orc6 associates with the", "associates with the orc", "with the orc 1", "the orc 1 5", "complex to form the", "to form the orc", "form the orc 1", "the orc 1 6", "1 6 complex", "complex ghosh et", "al. 2011 . the", "2011 . the association", ". the association of", "the association of orc6", "association of orc6 with", "of orc6 with the", "orc6 with the orc", "5 complex is", "complex is weak and", "is weak and it", "weak and it frequently", "and it frequently does", "it frequently does not", "frequently does not co", "does not co immunoprecipitate", "not co immunoprecipitate with", "co immunoprecipitate with the", "immunoprecipitate with the other", "with the other orc", "the other orc 1", "other orc 1 5", "1 5 subunits.", "5 subunits. orc4", "subunits. orc4 is the", "orc4 is the only", "is the only orc", "the only orc 1", "only orc 1 5", "1 5 subunit", "5 subunit that", "subunit that was shown", "that was shown to", "was shown to directly", "shown to directly bind", "to directly bind to", "directly bind to orc6", "to orc6 radichev", "orc6 radichev et", "al. 2006 . some", "2006 . some orc6", ". some orc6 mutations", "some orc6 mutations reported", "orc6 mutations reported in", "mutations reported in meier", "reported in meier gorlin", "in meier gorlin syndrome", "meier gorlin syndrome were", "gorlin syndrome were shown", "syndrome were shown to", "were shown to interfere", "shown to interfere with", "to interfere with orc6", "interfere with orc6 incorporation", "with orc6 incorporation into", "orc6 incorporation into the", "incorporation into the orc", "the orc balasov", "orc balasov et", "balasov et al. 2015", "et al. 2015 .", "human orc1 can associate with", "orc1 can associate with dna", "can associate with dna origin", "associate with dna origin of", "with dna origin of replication", "dna origin of replication sites", "origin of replication sites independently", "of replication sites independently of", "replication sites independently of other", "sites independently of other origin", "independently of other origin of", "of other origin of replication", "other origin of replication complex", "of replication complex orc", "complex orc subunits", "orc subunits hoshina", "subunits hoshina et al.", "et al. 2013 eladl", "al. 2013 eladl et", "2013 eladl et al.", "eladl et al. 2021 .", "et al. 2021 . orc1", "al. 2021 . orc1 localizes", "2021 . orc1 localizes to", ". orc1 localizes to condensed", "orc1 localizes to condensed chromosomes", "localizes to condensed chromosomes during", "to condensed chromosomes during early", "condensed chromosomes during early mitosis", "during early mitosis m", "early mitosis m phase", "m phase and serves", "phase and serves as", "and serves as a nucleating", "serves as a nucleating center", "as a nucleating center for", "a nucleating center for the", "nucleating center for the assembly", "center for the assembly of", "for the assembly of the", "the assembly of the orc", "assembly of the orc and", "the orc and subsequently", "and subsequently the", "subsequently the pre replication", "the pre replication complex. orc1", "pre replication complex. orc1 remains", "replication complex. orc1 remains associated", "complex. orc1 remains associated with", "orc1 remains associated with late", "remains associated with late replication", "associated with late replication origins", "with late replication origins throughout", "late replication origins throughout late", "replication origins throughout late g1.", "origins throughout late g1. upon", "throughout late g1. upon s", "late g1. upon s phase", "g1. upon s phase entry", "s phase entry orc1", "phase entry orc1 undergoes", "entry orc1 undergoes ubiquitin", "orc1 undergoes ubiquitin mediated degradation", "ubiquitin mediated degradation leading", "mediated degradation leading to", "degradation leading to dissociation", "leading to dissociation of the", "to dissociation of the orc", "dissociation of the orc from", "of the orc from chromatin", "orc from chromatin kara", "from chromatin kara et", "chromatin kara et al.", "kara et al. 2015 .

              most", "et al. 2015 .

              most human", "al. 2015 .

              most human replication", "2015 .

              most human replication origins", ".

              most human replication origins contain", "human replication origins contain guanine", "origins contain guanine g", "guanine g rich", "g rich sequences which", "rich sequences which may form", "sequences which may form g", "which may form g quadruplex", "form g quadruplex g4", "quadruplex g4 structures", "g4 structures besnard", "structures besnard et al.", "et al. 2012 and", "al. 2012 and these", "2012 and these g4", "and these g4 structures may", "these g4 structures may mediate", "g4 structures may mediate the", "structures may mediate the recognition", "may mediate the recognition of", "mediate the recognition of replication", "the recognition of replication origins", "recognition of replication origins by", "of replication origins by orc1", "origins by orc1 hoshina", "by orc1 hoshina et", "orc1 hoshina et al.", "et al. 2021 . besides", "al. 2021 . besides binding", "2021 . besides binding to", ". besides binding to nucleosome", "besides binding to nucleosome free", "binding to nucleosome free replication", "to nucleosome free replication origin", "nucleosome free replication origin dna", "replication origin dna orc1", "origin dna orc1 interacts", "dna orc1 interacts with", "orc1 interacts with neighboring nucleosomes", "with neighboring nucleosomes hizume", "neighboring nucleosomes hizume et", "nucleosomes hizume et al.", "al. 2013 in", "2013 in particular", "in particular with nucleosomes containing", "particular with nucleosomes containing histone", "with nucleosomes containing histone h4", "nucleosomes containing histone h4 dimethylated", "containing histone h4 dimethylated at", "histone h4 dimethylated at lysine", "h4 dimethylated at lysine 21", "at lysine 21 h4k20me2", "lysine 21 h4k20me2 mark", "h4k20me2 mark which", "mark which is", "which is enriched at replication", "is enriched at replication origins.", "enriched at replication origins. binding", "at replication origins. binding of", "replication origins. binding of orc1", "origins. binding of orc1 to", "binding of orc1 to h4k20me2", "of orc1 to h4k20me2 facilitates", "orc1 to h4k20me2 facilitates orc1", "to h4k20me2 facilitates orc1 binding", "h4k20me2 facilitates orc1 binding to", "facilitates orc1 binding to replication", "orc1 binding to replication origins", "binding to replication origins and", "to replication origins and orc", "replication origins and orc chromatin", "origins and orc chromatin loading", "orc chromatin loading kuo", "chromatin loading kuo et", "loading kuo et al.", "et al. 2012 zhang", "al. 2012 zhang et", "2012 zhang et al.", "zhang et al. 2015 .

              orc1", "et al. 2015 .

              orc1 binding", "al. 2015 .

              orc1 binding sites", "2015 .

              orc1 binding sites are", ".

              orc1 binding sites are universally", "binding sites are universally associated", "sites are universally associated with", "are universally associated with transcription", "universally associated with transcription start", "associated with transcription start sites", "transcription start sites tsss", "sites tsss of", "tsss of coding and", "of coding and non coding", "coding and non coding rnas.", "and non coding rnas. replication", "non coding rnas. replication origins", "coding rnas. replication origins associated", "rnas. replication origins associated with", "replication origins associated with moderate", "origins associated with moderate to", "associated with moderate to high", "with moderate to high transcription", "moderate to high transcription level", "to high transcription level tsss", "transcription level tsss belonging", "level tsss belonging to", "tsss belonging to coding", "to coding rnas fire", "coding rnas fire in", "rnas fire in early", "fire in early s phase", "early s phase while", "s phase while those", "phase while those associated", "while those associated with low", "those associated with low transcription", "associated with low transcription level", "with low transcription level tsss", "tsss belonging to non", "belonging to non coding rnas", "non coding rnas fire", "coding rnas fire throughout", "rnas fire throughout the", "fire throughout the s phase", "the s phase dellino", "s phase dellino et", "phase dellino et al.", "dellino et al. 2013 .

              orc2", "et al. 2013 .

              orc2 forms", "al. 2013 .

              orc2 forms a", "2013 .

              orc2 forms a heterodimer", ".

              orc2 forms a heterodimer with", "forms a heterodimer with orc3", "heterodimer with orc3 which", "with orc3 which is", "orc3 which is a", "which is a prerequisite for", "is a prerequisite for the", "a prerequisite for the association", "prerequisite for the association of", "for the association of orc5", "the association of orc5 and", "of orc5 and subsequently", "and subsequently orc4", "subsequently orc4 ranjan", "orc4 ranjan and gossen", "and gossen 2006 siddiqui", "gossen 2006 siddiqui and", "2006 siddiqui and stillman", "siddiqui and stillman 2007 .", "and stillman 2007 . orc1", "stillman 2007 . orc1 binds", "2007 . orc1 binds to", ". orc1 binds to the", "orc1 binds to the orc", "binds to the orc 2", "to the orc 2 5", "orc 2 5 complex", "2 5 complex in", "5 complex in the", "complex in the nucleus to", "in the nucleus to form", "the nucleus to form a", "nucleus to form a stable", "to form a stable orc", "form a stable orc 1", "a stable orc 1 5", "orc 1 5 complex", "5 complex radichev", "complex radichev et al.", "et al. 2006 ghosh", "al. 2006 ghosh et", "2006 ghosh et al.", "ghosh et al. 2011 .", "et al. 2011 . orc1", "al. 2011 . orc1 is", "2011 . orc1 is necessary", ". orc1 is necessary for", "orc1 is necessary for the", "is necessary for the association", "necessary for the association of", "for the association of the", "the association of the orc", "association of the orc 2", "of the orc 2 5", "2 5 complex to", "5 complex to chromatin", "complex to chromatin radichev", "to chromatin radichev et", "chromatin radichev et al.", "radichev et al. 2006 .", "et al. 2006 . the", "al. 2006 . the orc", "2006 . the orc 2", ". the orc 2 5", "2 5 complex exhibits", "5 complex exhibits a", "complex exhibits a tightly autoinhibited", "exhibits a tightly autoinhibited conformation", "tightly autoinhibited conformation with", "autoinhibited conformation with the", "conformation with the winged", "with the winged helix domain", "winged helix domain whd", "domain whd of", "whd of orc2 completely", "of orc2 completely blocking the", "orc2 completely blocking the central", "completely blocking the central dna", "blocking the central dna binding", "the central dna binding channel.", "central dna binding channel. binding", "dna binding channel. binding of", "binding channel. binding of orc1", "channel. binding of orc1 remodels", "binding of orc1 remodels the", "of orc1 remodels the whd", "orc1 remodels the whd of", "remodels the whd of orc2", "whd of orc2 moving", "of orc2 moving it", "orc2 moving it away", "moving it away from the", "it away from the central", "away from the central channel", "from the central channel and", "the central channel and partially", "central channel and partially relieving", "channel and partially relieving the", "and partially relieving the autoinhibition", "relieving the autoinhibition cheng", "the autoinhibition cheng et", "autoinhibition cheng et al.", "et al. 2020 jaremko", "al. 2020 jaremko et", "2020 jaremko et al.", "jaremko et al. 2020 .", "et al. 2020 . orc6", "al. 2020 . orc6 associates", "2020 . orc6 associates with", ". orc6 associates with the", "orc6 associates with the orc", "associates with the orc 1", "with the orc 1 5", "1 5 complex to", "5 complex to form", "complex to form the orc", "to form the orc 1", "form the orc 1 6", "orc 1 6 complex", "6 complex ghosh", "complex ghosh et al.", "et al. 2011 . the", "al. 2011 . the association", "2011 . the association of", ". the association of orc6", "the association of orc6 with", "association of orc6 with the", "of orc6 with the orc", "orc6 with the orc 1", "1 5 complex is", "5 complex is weak", "complex is weak and it", "is weak and it frequently", "weak and it frequently does", "and it frequently does not", "it frequently does not co", "frequently does not co immunoprecipitate", "does not co immunoprecipitate with", "not co immunoprecipitate with the", "co immunoprecipitate with the other", "immunoprecipitate with the other orc", "with the other orc 1", "the other orc 1 5", "orc 1 5 subunits.", "1 5 subunits. orc4", "5 subunits. orc4 is", "subunits. orc4 is the only", "orc4 is the only orc", "is the only orc 1", "the only orc 1 5", "orc 1 5 subunit", "1 5 subunit that", "5 subunit that was", "subunit that was shown to", "that was shown to directly", "was shown to directly bind", "shown to directly bind to", "to directly bind to orc6", "bind to orc6 radichev", "to orc6 radichev et", "orc6 radichev et al.", "et al. 2006 . some", "al. 2006 . some orc6", "2006 . some orc6 mutations", ". some orc6 mutations reported", "some orc6 mutations reported in", "orc6 mutations reported in meier", "mutations reported in meier gorlin", "reported in meier gorlin syndrome", "in meier gorlin syndrome were", "meier gorlin syndrome were shown", "gorlin syndrome were shown to", "syndrome were shown to interfere", "were shown to interfere with", "shown to interfere with orc6", "to interfere with orc6 incorporation", "interfere with orc6 incorporation into", "with orc6 incorporation into the", "orc6 incorporation into the orc", "into the orc balasov", "the orc balasov et", "orc balasov et al.", "balasov et al. 2015 ." ] }, { "record_id": "GLY_000594_1_1100", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "68867", "r hsa", "hsa 68867", "r hsa 68867" ] }, { "record_id": "GLY_000594_1_1100", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "assembly of", "of the", "the pre", "pre replicative", "replicative complex", "assembly of the", "of the pre", "the pre replicative", "pre replicative complex", "assembly of the pre", "of the pre replicative", "the pre replicative complex", "assembly of the pre replicative", "of the pre replicative complex", "dna replication", "replication pre", "pre initiation", "initiation in", "in eukaryotic", "eukaryotic cells", "cells begins", "begins with", "with the", "the formation", "formation of", "pre rc", "during the", "the late", "late m", "m phase", "phase and", "and continues", "continues in", "in the", "the g1", "g1 phase", "phase of", "the mitotic", "mitotic cell", "cell cycle", "a process", "process also", "also called", "called dna", "replication origin", "origin licensing.", "licensing. the", "the association", "association of", "of initiation", "initiation proteins", "mcm2 7", "the origin", "origin of", "of replication", "replication in", "in both", "both s.", "s. cerevisiae", "cerevisiae and", "and humans", "humans has", "has been", "been demonstrated", "demonstrated by", "by chromatin", "chromatin immunoprecipitation", "immunoprecipitation experiments.", "experiments. in", "in s.", "replicative complexes", "complexes are", "are assembled", "assembled from", "from late", "m to", "to g1.", "g1. in", "in mammalian", "mammalian cells", "cells as", "as well", "to g1", "as shown", "shown by", "by biochemical", "biochemical fractionation", "fractionation and", "and immunostaining.", "immunostaining. there", "there are", "are significant", "significant sequence", "sequence similarities", "similarities among", "among some", "some of", "the proteins", "proteins in", "replicative complex.", "complex. the", "the orc", "orc subunits", "subunits orc1", "orc4 and", "and orc5", "orc5 are", "are homologous", "homologous to", "to one", "one another", "another and", "and to", "to cdc6.", "cdc6. the", "the six", "six subunits", "subunits of", "the mcm2", "7 complex", "complex are", "one another.", "another. in", "in addition", "and the", "7 subunits", "are members", "members of", "the aaa+", "aaa+ superfamily", "superfamily of", "of atpases.", "atpases. since", "since the", "the initial", "initial identification", "identification of", "of these", "these pre", "rc components", "components other", "other factors", "factors that", "that participate", "participate in", "in this", "this complex", "complex have", "have been", "been found", "including cdt1", "cdt1 in", "in human", "s. pombe", "and s.", "cerevisiae cells.", "dna replication pre", "replication pre initiation", "pre initiation in", "initiation in eukaryotic", "in eukaryotic cells", "eukaryotic cells begins", "cells begins with", "begins with the", "with the formation", "the formation of", "formation of the", "complex pre", "rc during", "during the late", "the late m", "late m phase", "m phase and", "phase and continues", "and continues in", "continues in the", "in the g1", "the g1 phase", "g1 phase of", "phase of the", "of the mitotic", "the mitotic cell", "mitotic cell cycle", "cycle a", "a process also", "process also called", "also called dna", "called dna replication", "dna replication origin", "replication origin licensing.", "origin licensing. the", "licensing. the association", "the association of", "association of initiation", "of initiation proteins", "proteins orc", "orc cdc6", "cdc6 cdt1", "cdt1 mcm2", "7 with", "with the origin", "the origin of", "origin of 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phase and continues", "phase and continues in", "and continues in the", "continues in the g1", "in the g1 phase", "the g1 phase of", "g1 phase of the", "phase of the mitotic", "of the mitotic cell", "the mitotic cell cycle", "cell cycle a", "cycle a process", "a process also called", "process also called dna", "also called dna replication", "called dna replication origin", "dna replication origin licensing.", "replication origin licensing. the", "origin licensing. the association", "licensing. the association of", "the association of initiation", "association of initiation proteins", "initiation proteins orc", "cdt1 mcm2 7", "mcm2 7 with", "7 with the", "with the origin of", "the origin of replication", "origin of replication in", "of replication in both", "replication in both s.", "in both s. cerevisiae", "both s. cerevisiae and", "s. cerevisiae and humans", "cerevisiae and humans has", "and humans has been", "humans has been demonstrated", "has been demonstrated by", "been 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significant sequence similarities", "significant sequence similarities among", "sequence similarities among some", "similarities among some of", "among some of the", "some of the proteins", "of the proteins in", "the proteins in the", "proteins in the pre", "in the pre replicative", "the pre replicative complex.", "pre replicative complex. the", "replicative complex. the orc", "complex. the orc subunits", "the orc subunits orc1", "subunits orc1 orc4", "orc1 orc4 and", "orc4 and orc5 are", "and orc5 are homologous", "orc5 are homologous to", "are homologous to one", "homologous to one another", "to one another and", "one another and to", "another and to cdc6.", "and to cdc6. the", "to cdc6. the six", "cdc6. the six subunits", "the six subunits of", "six subunits of the", "subunits of the mcm2", "of the mcm2 7", "the mcm2 7 complex", "mcm2 7 complex are", "7 complex are homologous", "complex are homologous to", "homologous to one another.", "to one another. in", "one another. in addition", "in addition orc1", "cdc6 and the", "and the mcm2 7", "the mcm2 7 subunits", "7 subunits are", "subunits are members", "are members of the", "members of the aaa+", "of the aaa+ superfamily", "the aaa+ superfamily of", "aaa+ superfamily of atpases.", "superfamily of atpases. since", "of atpases. since the", "atpases. since the initial", "since the initial identification", "the initial identification of", "initial identification of these", "identification of these pre", "of these pre rc", "these pre rc components", "pre rc components other", "rc components other factors", "components other factors that", "other factors that participate", "factors that participate in", "that participate in this", "participate in this complex", "in this complex have", "this complex have been", "complex have been found", "been found including", "found including cdt1", "including cdt1 in human", "in human xenopus", "xenopus s. pombe", "s. pombe and", "pombe and s.", "and s. cerevisiae cells.", "dna replication pre initiation in", "replication pre initiation in eukaryotic", "pre initiation in eukaryotic cells", "initiation in eukaryotic cells begins", "in eukaryotic cells begins with", "eukaryotic cells begins with the", "cells begins with the formation", "begins with the formation of", "with the formation of the", "the formation of the pre", "formation of the pre replicative", "pre replicative complex pre", "replicative complex pre rc", "pre rc during the", "rc during the late", "during the late m phase", "the late m phase and", "late m phase and continues", "m phase and continues in", "phase and continues in the", "and continues in the g1", "continues in the g1 phase", "in the g1 phase of", "the g1 phase of the", "g1 phase of the mitotic", "phase of the mitotic cell", "of the mitotic cell cycle", "mitotic cell cycle a", "cell cycle a process", "cycle a process also", "a process also called dna", "process also called dna replication", "also called dna replication origin", "called dna replication origin licensing.", "dna replication origin licensing. the", "replication origin licensing. the association", "origin licensing. the association of", "licensing. the association of initiation", "the association of initiation proteins", "of initiation proteins orc", "proteins orc cdc6", "orc cdc6 cdt1", "cdc6 cdt1 mcm2", "mcm2 7 with the", "7 with the origin", "with the origin of replication", "the origin of replication in", "origin of replication in both", "of replication in both s.", "replication in both s. cerevisiae", "in both s. cerevisiae and", "both s. cerevisiae and humans", "s. cerevisiae and humans has", "cerevisiae and humans has been", "and humans has been demonstrated", "humans has been demonstrated by", "has been demonstrated by chromatin", "been demonstrated by chromatin immunoprecipitation", "demonstrated by chromatin immunoprecipitation experiments.", "by chromatin immunoprecipitation experiments. in", "chromatin immunoprecipitation experiments. in s.", "immunoprecipitation experiments. in s. cerevisiae", "in s. cerevisiae pre", "s. cerevisiae pre replicative", "cerevisiae pre replicative complexes", "pre replicative complexes are assembled", "replicative complexes are assembled from", "complexes are assembled from late", "are assembled from late m", "assembled from late m to", "from late m to g1.", "late m to g1. in", "m to g1. in mammalian", "to g1. in mammalian cells", "g1. in mammalian cells as", "in mammalian cells as well", "cells as well pre", "as well pre replicative", "well pre replicative complexes", "from late m to g1", "m to g1 as", "to g1 as shown", "g1 as shown by", "as shown by biochemical fractionation", "shown by biochemical fractionation and", "by biochemical fractionation and immunostaining.", "biochemical fractionation and immunostaining. there", "fractionation and immunostaining. there are", "and immunostaining. there are significant", "immunostaining. there are significant sequence", "there are significant sequence similarities", "are significant sequence similarities among", "significant sequence similarities among some", "sequence similarities among some of", "similarities among some of the", "among some of the proteins", "some of the proteins in", "of the proteins in the", "the proteins in the pre", "proteins in the pre replicative", "in the pre replicative complex.", "the pre replicative complex. the", "pre replicative complex. the orc", "replicative complex. the orc subunits", "complex. the orc subunits orc1", "orc subunits orc1 orc4", "subunits orc1 orc4 and", "orc1 orc4 and orc5", "orc4 and orc5 are homologous", "and orc5 are homologous to", "orc5 are homologous to one", "are homologous to one another", "homologous to one another and", "to one another and to", "one another and to cdc6.", "another and to cdc6. the", "and to cdc6. the six", "to cdc6. the six subunits", "cdc6. the six subunits of", "the six subunits of the", "six subunits of the mcm2", "subunits of the mcm2 7", "of the mcm2 7 complex", "the mcm2 7 complex are", "mcm2 7 complex are homologous", "7 complex are homologous to", "complex are homologous to one", "are homologous to one another.", "homologous to one another. in", "to one another. in addition", "another. in addition orc1", "addition orc1 orc4", "orc1 orc4 orc5", "orc4 orc5 cdc6", "orc5 cdc6 and", "cdc6 and the mcm2", "and the mcm2 7 subunits", "mcm2 7 subunits are", "7 subunits are members", "subunits are members of", "are members of the aaa+", "members of the aaa+ superfamily", "of the aaa+ superfamily of", "the aaa+ superfamily of atpases.", "aaa+ superfamily of atpases. since", "superfamily of atpases. since the", "of atpases. since the initial", "atpases. since the initial identification", "since the initial identification of", "the initial identification of these", "initial identification of these pre", "identification of these pre rc", "of these pre rc components", "these pre rc components other", "pre rc components other factors", "rc components other factors that", "components other factors that participate", "other factors that participate in", "factors that participate in this", "that participate in this complex", "participate in this complex have", "in this complex have been", "this complex have been found", "have been found including", "been found including cdt1", "found including cdt1 in", "cdt1 in human xenopus", "human xenopus s.", "s. pombe and s.", "pombe and s. cerevisiae" ] }, { "record_id": "GLY_000594_1_1101", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "68884", "r hsa", "hsa 68884", "r hsa 68884" ] }, { "record_id": "GLY_000594_1_1101", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitotic telophase/cytokinesis", "in this", "this final", "final phase", "phase of", "of mitosis", "new membranes", "membranes are", "are formed", "formed around", "around two", "two sets", "sets of", "of 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formed the", "formed the cdk2", "the cdk2 is phosphorylated", "cdk2 is phosphorylated by", "is phosphorylated by the", "phosphorylated by the wee1", "by the wee1 and", "the wee1 and myt1", "wee1 and myt1 kinases.", "and myt1 kinases. this", "myt1 kinases. this phosphorylation", "kinases. this phosphorylation keeps", "this phosphorylation keeps the", "phosphorylation keeps the cdk2", "keeps the cdk2 inactive.", "the cdk2 inactive. in", "cdk2 inactive. in yeast", "inactive. in yeast this", "in yeast this control", "yeast this control is", "this control is called", "control is called the", "is called the cell", "called the cell size", "the cell size checkpoint", "cell size checkpoint control.", "checkpoint control. the", "control. the dephosphorylation", "the dephosphorylation of the", "dephosphorylation of the cdk2", "of the cdk2 by", "the cdk2 by cdc25a", "cdk2 by cdc25a activates", "by cdc25a activates the", "cdc25a activates the cdk2", "the cdk2 and", "cdk2 and is", "and is 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amount", "tumorigenesis. the amount of", "the amount of cyclin", "amount of cyclin e", "of cyclin e protein", "cyclin e protein in", "e protein in the", "protein in the cell", "in the cell is", "the cell is controlled", "cell is controlled by", "is controlled by ubiquitin", "controlled by ubiquitin mediated", "by ubiquitin mediated proteolysis", "mediated proteolysis see", "proteolysis see woo", "see woo 2003", "woo 2003 .this", "2003 .this pathway has", ".this pathway has not", "pathway has not yet", "has not yet been", "not yet been annotated", "yet been annotated in", "been annotated in reactome.", "the transition from the g1", "transition from the g1 to", "from the g1 to s", "the g1 to s phase", "g1 to s phase is", "to s phase is controlled", "s phase is controlled by", "phase is controlled by the", "is controlled by the cyclin", "controlled by the cyclin e:cdk2", "by the cyclin e:cdk2 complexes.", "the cyclin e:cdk2 complexes. as", "cyclin e:cdk2 complexes. as the", "e:cdk2 complexes. as the cyclin", "complexes. as the cyclin e:cdk2", "as the cyclin e:cdk2 complexes", "the cyclin e:cdk2 complexes are", "cyclin e:cdk2 complexes are formed", "complexes are formed the", "are formed the cdk2", "formed the cdk2 is", "the cdk2 is phosphorylated by", "cdk2 is phosphorylated by the", "is phosphorylated by the wee1", "phosphorylated by the wee1 and", "by the wee1 and myt1", "the wee1 and myt1 kinases.", "wee1 and myt1 kinases. this", "and myt1 kinases. this phosphorylation", "myt1 kinases. this phosphorylation keeps", "kinases. this phosphorylation keeps the", "this phosphorylation keeps the cdk2", "phosphorylation keeps the cdk2 inactive.", "keeps the cdk2 inactive. in", "the cdk2 inactive. in yeast", "cdk2 inactive. in yeast this", "inactive. in yeast this control", "in yeast this control is", "yeast this control is called", "this control is called the", "control is called the cell", "is called the cell size", "called the cell size checkpoint", "the cell size checkpoint control.", "size checkpoint control. the", "checkpoint control. the dephosphorylation", "control. the dephosphorylation of", "the dephosphorylation of the cdk2", "dephosphorylation of the cdk2 by", "of the cdk2 by cdc25a", "the cdk2 by cdc25a activates", "cdk2 by cdc25a activates the", "by cdc25a activates the cdk2", "activates the cdk2 and", "the cdk2 and is", "cdk2 and is coordinated", "and is coordinated with the", "is coordinated with the cells", "coordinated with the cells reaching", "with the cells reaching the", "the cells reaching the proper", "cells reaching the proper size", "the proper size and", "proper size and with", "size and with the", "and with the dna synthesis", "with the dna synthesis machinery", "the dna synthesis machinery being", "dna synthesis machinery being ready.", "synthesis machinery being ready. the", "machinery being ready. the cdk2", "being ready. the cdk2 then", "ready. the cdk2 then phosphorylates", "the cdk2 then phosphorylates g1/s", "cdk2 then phosphorylates g1/s specific", "then phosphorylates g1/s specific proteins", "g1/s specific proteins including", "specific proteins including proteins", "proteins including proteins required", "including proteins required for dna", "proteins required for dna replication", "required for dna replication initiation.", "for dna replication initiation. the", "dna replication initiation. the beginning", "replication initiation. the beginning of", "initiation. the beginning of s", "the beginning of s phase", "beginning of s phase is", "of s phase is marked", "s phase is marked by", "phase is marked by the", "is marked by the first", "marked by the first nucleotide", "by the first nucleotide being", "the first nucleotide being laid", "first nucleotide being laid down", "nucleotide being laid down on", "being laid down on the", "laid down on the primer", "down on the primer during", "on the primer during dna", "the primer during dna replication", "primer during dna replication at", "during dna replication at the", "dna replication at the early", "replication at the early firing", "at the early firing origins.failure", "the early firing origins.failure to", "early firing origins.failure to appropriately", "firing origins.failure to appropriately regulate", "origins.failure to appropriately regulate cyclin", "to appropriately regulate cyclin e", "appropriately regulate cyclin e accumulation", "regulate cyclin e accumulation can", "cyclin e accumulation can lead", "e accumulation can lead to", "accumulation can lead to accelerated", "can lead to accelerated s", "lead to accelerated s phase", "to accelerated s phase entry", "s phase entry genetic", "phase entry genetic instability", "genetic instability and tumorigenesis.", "instability and tumorigenesis. the", "and tumorigenesis. the amount of", "tumorigenesis. the amount of cyclin", "the amount of cyclin e", "amount of cyclin e protein", "of cyclin e protein in", "cyclin e protein in the", "e protein in the cell", "protein in the cell is", "in the cell is controlled", "the cell is controlled by", "cell is controlled by ubiquitin", "is controlled by ubiquitin mediated", "controlled by ubiquitin mediated proteolysis", "ubiquitin mediated proteolysis see", "mediated proteolysis see woo", "see woo 2003 .this", "woo 2003 .this pathway", "2003 .this pathway has not", ".this pathway has not yet", "pathway has not yet been", "has not yet been annotated", "not yet been annotated in", "yet been annotated in reactome." ] }, { "record_id": "GLY_000594_1_1105", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "69205", "r hsa", "hsa 69205", "r hsa 69205" ] }, { "record_id": "GLY_000594_1_1105", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "g1/s specific", "specific transcription", "g1/s specific transcription", "the e2f", "e2f family", "family of", "of transcription", "transcription factors", "factors regulate", "regulate the", "the transition", "transition from", "from the", "the g1", "g1 to", "to the", "the s", "s phase", "phase in", "in the", "the cell", "cell cycle.", "cycle. e2f", "e2f activity", "activity is", "is regulated", "regulated by", "by members", "members of", "of the", "the retinoblastoma", "retinoblastoma protein", "resulting in", "the tight", "tight control", "control of", "the expression", "expression of", "of e2f", "e2f responsive", "responsive genes.", "genes. phosphorylation", "phosphorylation of", "of prb", "prb by", "by cyclin", "cyclin d:cdk", "d:cdk complexes", "complexes releases", "releases prb", "prb from", "from e2f", "inducing e2f", "e2f targeted", "targeted genes", "genes such", "such as", "as cyclin", "cyclin e.

              e2f1", "e.

              e2f1 binds", "binds to", "to e2f", "e2f binding", "binding sites", "sites on", "on the", "the genome", "genome activating", "activating the", "the synthesis", "synthesis of", "the target", "target proteins.", "proteins. for", "for annotation", "annotation purposes", "the reactions", "reactions regulated", "by e2f1", "e2f1 are", "are grouped", "grouped under", "under this", "this pathway", "pathway and", "and information", "information about", "about the", "target genes", "genes alone", "alone are", "are displayed", "displayed for", "annotation purposes.
              cellular", "purposes.
              cellular targets", "targets for", "for activation", "activation by", "e2f1 include", "include thymidylate", "thymidylate synthase", "degregori et", "et al.", "al. 1995", "giangrande et", "al. 2004", "dihydrofolate reductase", "wells et", "al. 1997", "darbinian et", "al. 1999", "furukawa et", "al. 1994", "zhu et", "cyclin a1", "liu et", "al. 1998", "yan et", "ohtani et", "yoshida and", "and inoue", "inoue 2004", "arata et", "al. 2000", "cyclin e", "hsu et", "al. 2002", "and orc1", "al. 1996", "1998 .", ". the", "the activation", "activation of", "of tk1", "dou et", "and cdc25a", "vigo et", "e2f1 is", "is conserved", "conserved in", "in drosophila", "duronio and", "and o'farrell", "o'farrell 1994", "reis and", "and edgar", "edgar 2004", "2004 .
              rrm2", ".
              rrm2 protein", "protein is", "is involved", "involved in", "in dntp", "dntp level", "level regulation", "regulation and", "and activation", "of this", "this enzyme", "enzyme results", "results in", "in higher", "higher levels", "levels of", "of dntps", "dntps in", "in anticipation", "anticipation of", "of s", "s phase.", "phase. e2f", "e2f activation", "of rrm2", "rrm2 has", "has been", "been shown", "shown also", "also in", "drosophila by", "by duronio", "1994 .", ". e2f1", "e2f1 activation", "of cdc45", "cdc45 is", "is shown", "shown in", "in mouse", "mouse cells", "cells by", "by using", "using human", "human e2f1", "e2f1 construct", "2000 .", ". cyclin", "e is", "is also", "also transcriptionally", "transcriptionally regulated", "by e2f1.", "e2f1. cyclin", "e protein", "protein plays", "plays important", "important role", "role in", "transition of", "of g1", "g1 in", "in s", "phase by", "by associating", "associating with", "with cdk2", "1996 .", "e2f1 mediated", "mediated activation", "of pcna", "pcna has", "been demonstrated", "demonstrated in", "and in", "in some", "some human", "human cells", "using recombinant", "recombinant adenovirus", "adenovirus constructs", "1995 .", "the dna", "dna polymerase", "polymerase alpha", "alpha subunit", "subunit p180", "human cells.", "cells. it", "it has", "has also", "also been", "by ohtani", "ohtani and", "and nevins", ". it", "been observed", "observed in", "drosophila that", "that e2f1", "e2f1 induced", "induced expression", "of orc1", "orc1 stimulates", "stimulates orc1", "orc1 6", "6 complex", "complex formation", "formation and", "and binding", "binding to", "the origin", "origin of", "of replication", "asano and", "and wharton", "wharton 1999", "1999 .", ". orc1", "6 recruit", "recruit cdc6", "cdc6 and", "and cdt1", "cdt1 that", "that are", "are required", "required to", "to recruit", "recruit the", "the mcm2", "mcm2 7", "7 replication", "replication helicases.", "helicases. e2f1", "e2f1 regulation", "regulation incorporates", "incorporates a", "a feedback", "feedback mechanism", "mechanism wherein", "wherein geminin", "can inhibit", "inhibit mcm2", "7 recruitment", "recruitment of", "complex by", "by interacting", "interacting with", "with cdc6/cdt1.", "cdc6/cdt1. the", "of cdc25a", "cdc25a and", "and tk1", "e2f1 has", "been inferred", "inferred from", "from similar", "similar events", "events in", "duronio rj", "rj and", "2004 .", "e2f1 activates", "activates string", "that in", "in turn", "turn activates", "activates the", "the complex", "complex of", "of cyclin", "cyclin b", "b and", "and cdk1.", "cdk1. a", "a similar", "similar phenomenon", "phenomenon has", "mouse nih", "nih 3t3", "3t3 cells", "cells and", "in rat1", "rat1 cells.", "the e2f family", "e2f family of", "family of transcription", "of transcription factors", "transcription factors regulate", "factors regulate the", "regulate the transition", "the transition from", "transition from the", "from the g1", "the g1 to", "g1 to the", "to the s", "the s phase", "s phase in", "phase in the", "in the cell", "the cell cycle.", "cell cycle. e2f", "cycle. e2f activity", "e2f activity is", "activity is regulated", "is regulated by", "regulated by members", "by members of", "members of the", "of the retinoblastoma", "the retinoblastoma protein", "protein prb", "prb family", "family resulting", "resulting in the", "in the tight", "the tight control", "tight control of", "control of the", "of the expression", "the expression of", "expression of e2f", "of e2f responsive", "e2f responsive genes.", "responsive genes. phosphorylation", "genes. phosphorylation of", "phosphorylation of prb", "of prb by", "prb by cyclin", "by cyclin d:cdk", "cyclin d:cdk complexes", "d:cdk complexes releases", "complexes releases prb", "releases prb from", "prb from e2f", "e2f inducing", "inducing e2f targeted", "e2f targeted genes", "targeted genes such", "genes such as", "such as cyclin", "as cyclin e.

              e2f1", "cyclin e.

              e2f1 binds", "e.

              e2f1 binds to", "binds to e2f", "to e2f binding", "e2f binding sites", "binding sites on", "sites on the", "on the genome", "the genome activating", "genome activating the", "activating the synthesis", "the synthesis of", "synthesis of the", "of the target", "the target proteins.", "target proteins. for", "proteins. for annotation", "for annotation purposes", "purposes the", "the reactions regulated", "reactions regulated by", "regulated by e2f1", "by e2f1 are", "e2f1 are grouped", "are grouped under", "grouped under this", "under this pathway", "this pathway and", "pathway and information", "and information about", "information about the", "about the target", "the target genes", "target genes alone", "genes alone are", "alone are displayed", "are displayed for", "displayed for annotation", "for annotation purposes.
              cellular", "annotation purposes.
              cellular targets", "purposes.
              cellular targets for", "targets for activation", "for activation by", "activation by e2f1", "by e2f1 include", "e2f1 include thymidylate", "include thymidylate synthase", "synthase tyms", "degregori et al.", "et al. 1995", "rir2 rrm2", "1995 giangrande", "giangrande et al.", "et al. 2004", "reductase dhfr", "1995 wells", "wells et al.", "et al. 1997", "1997 darbinian", "darbinian et al.", "et al. 1999", "cdc2 cdk1", "furukawa et al.", "et al. 1994", "1994 degregori", "1995 zhu", "zhu et al.", "a1 ccna1", "1995 liu", "liu et al.", "et al. 1998", "cdc6 degregori", "1995 yan", "yan et al.", "1998 ohtani", "ohtani et al.", "cdt1 yoshida", "yoshida and inoue", "and inoue 2004", "cdc45 arata", "arata et al.", "et al. 2000", "e ccne1", "emi1 fbxo5", "hsu et al.", "et al. 2002", "orc1 ohtani", "et al. 1996", "1996 ohtani", "al. 1998 .", "1998 . the", ". the activation", "the activation of", "activation of tk1", "tk1 dnk1", "dou et al.", "2004 and", "cdc25a degregori", "1995 vigo", "vigo et al.", "1999 by", "by e2f1 is", "e2f1 is conserved", "is conserved in", "conserved in drosophila", "drosophila duronio", "duronio and o'farrell", "and o'farrell 1994", "1994 reis", "reis and edgar", "and edgar 2004", "edgar 2004 .
              rrm2", "2004 .
              rrm2 protein", ".
              rrm2 protein is", "protein is involved", "is involved in", "involved in dntp", "in dntp level", "dntp level regulation", "level regulation and", "regulation and activation", "and activation of", "activation of this", "of this enzyme", "this enzyme results", "enzyme results in", "results in higher", "in higher levels", "higher levels of", "levels of dntps", "of dntps in", "dntps in anticipation", "in anticipation of", "anticipation of s", "of s phase.", "s phase. e2f", "phase. e2f activation", "e2f activation of", "activation of rrm2", "of rrm2 has", "rrm2 has been", "has been shown", "been shown also", "shown also in", "also in drosophila", "in drosophila by", "drosophila by duronio", "by duronio and", "1994 . e2f1", ". e2f1 activation", "e2f1 activation of", "activation of cdc45", "of cdc45 is", "cdc45 is shown", "is shown in", "shown in mouse", "in mouse cells", "mouse cells by", "cells by using", "by using human", "using human e2f1", "human e2f1 construct", "construct arata", "al. 2000 .", "2000 . cyclin", ". cyclin e", "cyclin e is", "e is also", "is also transcriptionally", "also transcriptionally regulated", "transcriptionally regulated by", "regulated by e2f1.", "by e2f1. cyclin", "e2f1. cyclin e", "cyclin e protein", "e protein plays", "protein plays important", "plays important role", "important role in", "role in the", "in the transition", "the transition of", "transition of g1", "of g1 in", "g1 in s", "in s phase", "s phase by", "phase by associating", "by associating with", "associating with cdk2", "cdk2 ohtani", "al. 1996 .", "1996 . e2f1", ". e2f1 mediated", "e2f1 mediated activation", "mediated activation of", "activation of pcna", "of pcna has", "pcna has been", "has been demonstrated", "been demonstrated in", "demonstrated in drosophila", "1994 and", "and in some", "in some human", "some human cells", "human cells by", "by using recombinant", "using recombinant adenovirus", "recombinant adenovirus constructs", "constructs degregori", "al. 1995 .", "1995 . e2f1", "activation of the", "of the dna", "the dna polymerase", "dna polymerase alpha", "polymerase alpha subunit", "alpha subunit p180", "p180 pola1", "pola1 has", "demonstrated in some", "some human cells.", "human cells. it", "cells. it has", "it has also", "has also been", "also been demonstrated", "drosophila by ohtani", "by ohtani and", "ohtani and nevins", "nevins 1994", "1994 . it", ". it has", "it has been", "has been observed", "been observed in", "observed in drosophila", "in drosophila that", "drosophila that e2f1", "that e2f1 induced", "e2f1 induced expression", "induced expression of", "expression of orc1", "of orc1 stimulates", "orc1 stimulates orc1", "stimulates orc1 6", "orc1 6 complex", "6 complex formation", "complex formation and", "formation and binding", "and binding to", "binding to the", "to the origin", "the origin of", "origin of replication", "replication asano", "asano and wharton", "and wharton 1999", "wharton 1999 .", "1999 . orc1", ". orc1 6", "orc1 6 recruit", "6 recruit cdc6", "recruit cdc6 and", "cdc6 and cdt1", "and cdt1 that", "cdt1 that are", "that are required", "are required to", "required to recruit", "to recruit the", "recruit the mcm2", "the mcm2 7", "mcm2 7 replication", "7 replication helicases.", "replication helicases. e2f1", "helicases. e2f1 regulation", "e2f1 regulation incorporates", "regulation incorporates a", "incorporates a feedback", "a feedback mechanism", "feedback mechanism wherein", "mechanism wherein geminin", "geminin gmnn", "gmnn can", "can inhibit mcm2", "inhibit mcm2 7", "mcm2 7 recruitment", "7 recruitment of", "recruitment of orc1", "of orc1 6", "6 complex by", "complex by interacting", "by interacting with", "interacting with cdc6/cdt1.", "with cdc6/cdt1. the", "cdc6/cdt1. the activation", "activation of cdc25a", "of cdc25a and", "cdc25a and tk1", "dnk1 by", "by e2f1 has", "e2f1 has been", "has been inferred", "been inferred from", "inferred from similar", "from similar events", "similar events in", "events in drosophila", "duronio rj and", "rj and o'farrell", "edgar 2004 .", "2004 . e2f1", ". e2f1 activates", "e2f1 activates string", "string cdc25", "cdc25 that", "that in turn", "in turn activates", "turn activates the", "activates the complex", "the complex of", "complex of cyclin", "of cyclin b", "cyclin b and", "b and cdk1.", "and cdk1. a", "cdk1. a similar", "a similar phenomenon", "similar phenomenon has", "phenomenon has been", "observed in mouse", "in mouse nih", "mouse nih 3t3", "nih 3t3 cells", "3t3 cells and", "cells and in", "and in rat1", "in rat1 cells.", "the e2f family of", "e2f family of transcription", "family of transcription factors", "of transcription factors regulate", "transcription factors regulate the", "factors regulate the transition", "regulate the transition from", "the transition from the", "transition from the g1", "from the g1 to", "the g1 to the", "g1 to the s", "to the s phase", "the s phase in", "s phase in the", "phase in the cell", "in the cell cycle.", "the cell cycle. e2f", "cell cycle. e2f activity", "cycle. e2f activity is", "e2f activity is regulated", "activity is regulated by", "is regulated by members", "regulated by members of", "by members of the", "members of the retinoblastoma", "of the retinoblastoma protein", "retinoblastoma protein prb", "family resulting in", "resulting in the tight", "in the tight control", "the tight control of", "tight control of the", "control of the expression", "of the expression of", "the expression of e2f", "expression of e2f responsive", "of e2f responsive genes.", "e2f responsive genes. phosphorylation", "responsive genes. phosphorylation of", "genes. phosphorylation of prb", "phosphorylation of prb by", "of prb by cyclin", "prb by cyclin d:cdk", "by cyclin d:cdk complexes", "cyclin d:cdk complexes releases", "d:cdk complexes releases prb", "complexes releases prb from", "releases prb from e2f", "from e2f inducing", "e2f inducing e2f", "inducing e2f targeted genes", "e2f targeted genes such", "targeted genes such as", "genes such as cyclin", "such as cyclin e.

              e2f1", "as cyclin e.

              e2f1 binds", "cyclin e.

              e2f1 binds to", "e.

              e2f1 binds to e2f", "binds to e2f binding", "to e2f binding sites", "e2f binding sites on", "binding sites on the", "sites on the genome", "on the genome activating", "the genome activating the", "genome activating the synthesis", "activating the synthesis of", "the synthesis of the", "synthesis of the target", "of the target proteins.", "the target proteins. for", "target proteins. for annotation", "proteins. for annotation purposes", "annotation purposes the", "purposes the reactions", "the reactions regulated by", "reactions regulated by e2f1", "regulated by e2f1 are", "by e2f1 are grouped", "e2f1 are grouped under", "are grouped under this", "grouped under this pathway", "under this pathway and", "this pathway and information", "pathway and information about", "and information about the", "information about the target", "about the target genes", "the target genes alone", "target genes alone are", "genes alone are displayed", "alone are displayed for", "are displayed for annotation", "displayed for annotation purposes.
              cellular", "for annotation purposes.
              cellular targets", "annotation purposes.
              cellular targets for", "purposes.
              cellular targets for activation", "targets for activation by", "for activation by e2f1", "activation by e2f1 include", "by e2f1 include thymidylate", "e2f1 include thymidylate synthase", "thymidylate synthase tyms", "tyms degregori", "degregori et al. 1995", "1995 rir2", "rrm2 degregori", "al. 1995 giangrande", "1995 giangrande et", "giangrande et al. 2004", "2004 dihydrofolate", "dihydrofolate reductase dhfr", "dhfr degregori", "al. 1995 wells", "1995 wells et", "wells et al. 1997", "al. 1997 darbinian", "1997 darbinian et", "darbinian et al. 1999", "1999 cdc2", "cdk1 furukawa", "furukawa et al. 1994", "al. 1994 degregori", "1994 degregori et", "al. 1995 zhu", "1995 zhu et", "zhu et al. 2004", "2004 cyclin", "cyclin a1 ccna1", "ccna1 degregori", "al. 1995 liu", "1995 liu et", "liu et al. 1998", "1998 cdc6", "cdc6 degregori et", "al. 1995 yan", "1995 yan et", "yan et al. 1998", "al. 1998 ohtani", "1998 ohtani et", "ohtani et al. 1998", "1998 cdt1", "cdt1 yoshida and", "yoshida and inoue 2004", "2004 cdc45", "cdc45 arata et", "arata et al. 2000", "2000 cyclin", "cyclin e ccne1", "ccne1 ohtani", "ohtani et al. 1995", "1995 emi1", "fbxo5 hsu", "hsu et al. 2002", "2002 and", "and orc1 ohtani", "orc1 ohtani et", "ohtani et al. 1996", "al. 1996 ohtani", "1996 ohtani et", "et al. 1998 .", "al. 1998 . the", "1998 . the activation", ". the activation of", "the activation of tk1", "of tk1 dnk1", "dnk1 dou", "dou et al. 1994", "al. 2004 and", "2004 and cdc25a", "and cdc25a degregori", "cdc25a degregori et", "al. 1995 vigo", "1995 vigo et", "vigo et al. 1999", "al. 1999 by", "1999 by e2f1", "by e2f1 is conserved", "e2f1 is conserved in", "is conserved in drosophila", "in drosophila duronio", "drosophila duronio and", "duronio and o'farrell 1994", "o'farrell 1994 reis", "1994 reis and", "reis and edgar 2004", "and edgar 2004 .
              rrm2", "edgar 2004 .
              rrm2 protein", "2004 .
              rrm2 protein is", ".
              rrm2 protein is involved", "protein is involved in", "is involved in dntp", "involved in dntp level", "in dntp level regulation", "dntp level regulation and", "level regulation and activation", "regulation and activation of", "and activation of this", "activation of this enzyme", "of this enzyme results", "this enzyme results in", "enzyme results in higher", "results in higher levels", "in higher levels of", "higher levels of dntps", "levels of dntps in", "of dntps in anticipation", "dntps in anticipation of", "in anticipation of s", "anticipation of s phase.", "of s phase. e2f", "s phase. e2f activation", "phase. e2f activation of", "e2f activation of rrm2", "activation of rrm2 has", "of rrm2 has been", "rrm2 has been shown", "has been shown also", "been shown also in", "shown also in drosophila", "also in drosophila by", "in drosophila by duronio", "drosophila by duronio and", "by duronio and o'farrell", "o'farrell 1994 .", "1994 . e2f1 activation", ". e2f1 activation of", "e2f1 activation of cdc45", "activation of cdc45 is", "of cdc45 is shown", "cdc45 is shown in", "is shown in mouse", "shown in mouse cells", "in mouse cells by", "mouse cells by using", "cells by using human", "by using human e2f1", "using human e2f1 construct", "e2f1 construct arata", "construct arata et", "et al. 2000 .", "al. 2000 . cyclin", "2000 . cyclin e", ". cyclin e is", "cyclin e is also", "e is also transcriptionally", "is also transcriptionally regulated", "also transcriptionally regulated by", "transcriptionally regulated by e2f1.", "regulated by e2f1. cyclin", "by e2f1. cyclin e", "e2f1. cyclin e protein", "cyclin e protein plays", "e protein plays important", "protein plays important role", "plays important role in", "important role in the", "role in the transition", "in the transition of", "the transition of g1", "transition of g1 in", "of g1 in s", "g1 in s phase", "in s phase by", "s phase by associating", "phase by associating with", "by associating with cdk2", "with cdk2 ohtani", "cdk2 ohtani et", "et al. 1996 .", "al. 1996 . e2f1", "1996 . e2f1 mediated", ". e2f1 mediated activation", "e2f1 mediated activation of", "mediated activation of pcna", "activation of pcna has", "of pcna has been", "pcna has been demonstrated", "has been demonstrated in", "been demonstrated in drosophila", "o'farrell 1994 and", "1994 and in", "and in some human", "in some human cells", "some human cells by", "human cells by using", "cells by using recombinant", "by using recombinant adenovirus", "using recombinant adenovirus constructs", "adenovirus constructs degregori", "constructs degregori et", "et al. 1995 .", "al. 1995 . e2f1", "1995 . e2f1 mediated", "mediated activation of the", "activation of the dna", "of the dna polymerase", "the dna polymerase alpha", "dna polymerase alpha subunit", "polymerase alpha subunit p180", "subunit p180 pola1", "pola1 has been", "been demonstrated in some", "demonstrated in some human", "in some human cells.", "some human cells. it", "human cells. it has", "cells. it has also", "it has also been", "has also been demonstrated", "also been demonstrated in", "demonstrated in drosophila by", "in drosophila by ohtani", "drosophila by ohtani and", "by ohtani and nevins", "and nevins 1994", "nevins 1994 .", "1994 . it has", ". it has been", "it has been observed", "has been observed in", "been observed in drosophila", "observed in drosophila that", "in drosophila that e2f1", "drosophila that e2f1 induced", "that e2f1 induced expression", "e2f1 induced expression of", "induced expression of orc1", "expression of orc1 stimulates", "of orc1 stimulates orc1", "orc1 stimulates orc1 6", "stimulates orc1 6 complex", "orc1 6 complex formation", "6 complex formation and", "complex formation and binding", "formation and binding to", "and binding to the", "binding to the origin", "to the origin of", "the origin of replication", "of replication asano", "replication asano and", "asano and wharton 1999", "and wharton 1999 .", "wharton 1999 . orc1", "1999 . orc1 6", ". orc1 6 recruit", "orc1 6 recruit cdc6", "6 recruit cdc6 and", "recruit cdc6 and cdt1", "cdc6 and cdt1 that", "and cdt1 that are", "cdt1 that are required", "that are required to", "are required to recruit", "required to recruit the", "to recruit the mcm2", "recruit the mcm2 7", "the mcm2 7 replication", "mcm2 7 replication helicases.", "7 replication helicases. e2f1", "replication helicases. e2f1 regulation", "helicases. e2f1 regulation incorporates", "e2f1 regulation incorporates a", "regulation incorporates a feedback", "incorporates a feedback mechanism", "a feedback mechanism wherein", "feedback mechanism wherein geminin", "wherein geminin gmnn", "gmnn can inhibit", "can inhibit mcm2 7", "inhibit mcm2 7 recruitment", "mcm2 7 recruitment of", "7 recruitment of orc1", "recruitment of orc1 6", "of orc1 6 complex", "orc1 6 complex by", "6 complex by interacting", "complex by interacting with", "by interacting with cdc6/cdt1.", "interacting with cdc6/cdt1. the", "with cdc6/cdt1. the activation", "cdc6/cdt1. the activation of", "the activation of cdc25a", "activation of cdc25a and", "of cdc25a and tk1", "and tk1 dnk1", "dnk1 by e2f1", "by e2f1 has been", "e2f1 has been inferred", "has been inferred from", "been inferred from similar", "inferred from similar events", "from similar events in", "similar events in drosophila", "drosophila duronio rj", "duronio rj and o'farrell", "rj and o'farrell 1994", "and edgar 2004 .", "edgar 2004 . e2f1", "2004 . e2f1 activates", ". e2f1 activates string", "activates string cdc25", "cdc25 that in", "that in turn activates", "in turn activates the", "turn activates the complex", "activates the complex of", "the complex of cyclin", "complex of cyclin b", "of cyclin b and", "cyclin b and cdk1.", "b and cdk1. a", "and cdk1. a similar", "cdk1. a similar phenomenon", "a similar phenomenon has", "similar phenomenon has been", "phenomenon has been observed", "been observed in mouse", "observed in mouse nih", "in mouse nih 3t3", "mouse nih 3t3 cells", "nih 3t3 cells and", "3t3 cells and in", "cells and in rat1", "and in rat1 cells.", "the e2f family of transcription", "e2f family of transcription factors", "family of transcription factors regulate", "of transcription factors regulate the", "transcription factors regulate the transition", "factors regulate the transition from", "regulate the transition from the", "the transition from the g1", "transition from the g1 to", "from the g1 to the", "the g1 to the s", "g1 to the s phase", "to the s phase in", "the s phase in the", "s phase in the cell", "phase in the cell cycle.", "in the cell cycle. e2f", "the cell cycle. e2f activity", "cell cycle. e2f activity is", "cycle. e2f activity is regulated", "e2f activity is regulated by", "activity is regulated by members", "is regulated by members of", "regulated by members of the", "by members of the retinoblastoma", "members of the retinoblastoma protein", "the retinoblastoma protein prb", "protein prb family", "prb family resulting", "family resulting in the", "resulting in the tight control", "in the tight control of", "the tight control of the", "tight control of the expression", "control of the expression of", "of the expression of e2f", "the expression of e2f responsive", "expression of e2f responsive genes.", "of e2f responsive genes. phosphorylation", "e2f responsive genes. phosphorylation of", "responsive genes. phosphorylation of prb", "genes. phosphorylation of prb by", "phosphorylation of prb by cyclin", "of prb by cyclin d:cdk", "prb by cyclin d:cdk complexes", "by cyclin d:cdk complexes releases", "cyclin d:cdk complexes releases prb", "d:cdk complexes releases prb from", "complexes releases prb from e2f", "prb from e2f inducing", "from e2f inducing e2f", "e2f inducing e2f targeted", "inducing e2f targeted genes such", "e2f targeted genes such as", "targeted genes such as cyclin", "genes such as cyclin e.

              e2f1", "such as cyclin e.

              e2f1 binds", "as cyclin e.

              e2f1 binds to", "cyclin e.

              e2f1 binds to e2f", "e.

              e2f1 binds to e2f binding", "binds to e2f binding sites", "to e2f binding sites on", "e2f binding sites on the", "binding sites on the genome", "sites on the genome activating", "on the genome activating the", "the genome activating the synthesis", "genome activating the synthesis of", "activating the synthesis of the", "the synthesis of the target", "synthesis of the target proteins.", "of the target proteins. for", "the target proteins. for annotation", "target proteins. for annotation purposes", "for annotation purposes the", "annotation purposes the reactions", "purposes the reactions regulated", "the reactions regulated by e2f1", "reactions regulated by e2f1 are", "regulated by e2f1 are grouped", "by e2f1 are grouped under", "e2f1 are grouped under this", "are grouped under this pathway", "grouped under this pathway and", "under this pathway and information", "this pathway and information about", "pathway and information about the", "and information about the target", "information about the target genes", "about the target genes alone", "the target genes alone are", "target genes alone are displayed", "genes alone are displayed for", "alone are displayed for annotation", "are displayed for annotation purposes.
              cellular", "displayed for annotation purposes.
              cellular targets", "for annotation purposes.
              cellular targets for", "annotation purposes.
              cellular targets for activation", "purposes.
              cellular targets for activation by", "targets for activation by e2f1", "for activation by e2f1 include", "activation by e2f1 include thymidylate", "by e2f1 include thymidylate synthase", "include thymidylate synthase tyms", "tyms degregori et", "al. 1995 rir2", "rrm2 degregori et", "et al. 1995 giangrande", "al. 1995 giangrande et", "1995 giangrande et al.", "al. 2004 dihydrofolate", "2004 dihydrofolate reductase", "dhfr degregori et", "et al. 1995 wells", "al. 1995 wells et", "1995 wells et al.", "et al. 1997 darbinian", "al. 1997 darbinian et", "1997 darbinian et al.", "al. 1999 cdc2", "cdk1 furukawa et", "et al. 1994 degregori", "al. 1994 degregori et", "1994 degregori et al.", "et al. 1995 zhu", "al. 1995 zhu et", "1995 zhu et al.", "al. 2004 cyclin", "2004 cyclin a1", "ccna1 degregori et", "et al. 1995 liu", "al. 1995 liu et", "1995 liu et al.", "al. 1998 cdc6", "cdc6 degregori et al.", "et al. 1995 yan", "al. 1995 yan et", "1995 yan et al.", "et al. 1998 ohtani", "al. 1998 ohtani et", "1998 ohtani et al.", "al. 1998 cdt1", "cdt1 yoshida and inoue", "inoue 2004 cdc45", "cdc45 arata et al.", "al. 2000 cyclin", "2000 cyclin e", "ccne1 ohtani et", "al. 1995 emi1", "fbxo5 hsu et", "al. 2002 and", "2002 and orc1", "and orc1 ohtani et", "orc1 ohtani et al.", "et al. 1996 ohtani", "al. 1996 ohtani et", "1996 ohtani et al.", "ohtani et al. 1998 .", "et al. 1998 . the", "al. 1998 . the activation", "1998 . the activation of", ". the activation of tk1", "activation of tk1 dnk1", "dnk1 dou et", "et al. 2004 and", "al. 2004 and cdc25a", "and cdc25a degregori et", "cdc25a degregori et al.", "et al. 1995 vigo", "al. 1995 vigo et", "1995 vigo et al.", "et al. 1999 by", "al. 1999 by e2f1", "1999 by e2f1 is", "by e2f1 is conserved in", "e2f1 is conserved in drosophila", "conserved in drosophila duronio", "in drosophila duronio and", "drosophila duronio and o'farrell", "and o'farrell 1994 reis", "o'farrell 1994 reis and", "1994 reis and edgar", "reis and edgar 2004 .
              rrm2", "and edgar 2004 .
              rrm2 protein", "edgar 2004 .
              rrm2 protein is", "2004 .
              rrm2 protein is involved", ".
              rrm2 protein is involved in", "protein is involved in dntp", "is involved in dntp level", "involved in dntp level regulation", "in dntp level regulation and", "dntp level regulation and activation", "level regulation and activation of", "regulation and activation of this", "and activation of this enzyme", "activation of this enzyme results", "of this enzyme results in", "this enzyme results in higher", "enzyme results in higher levels", "results in higher levels of", "in higher levels of dntps", "higher levels of dntps in", "levels of dntps in anticipation", "of dntps in anticipation of", "dntps in anticipation of s", "in anticipation of s phase.", "anticipation of s phase. e2f", "of s phase. e2f activation", "s phase. e2f activation of", "phase. e2f activation of rrm2", "e2f activation of rrm2 has", "activation of rrm2 has been", "of rrm2 has been shown", "rrm2 has been shown also", "has been shown also in", "been shown also in drosophila", "shown also in drosophila by", "also in drosophila by duronio", "in drosophila by duronio and", "drosophila by duronio and o'farrell", "and o'farrell 1994 .", "o'farrell 1994 . e2f1", "1994 . e2f1 activation of", ". e2f1 activation of cdc45", "e2f1 activation of cdc45 is", "activation of cdc45 is shown", "of cdc45 is shown in", "cdc45 is shown in mouse", "is shown in mouse cells", "shown in mouse cells by", "in mouse cells by using", "mouse cells by using human", "cells by using human e2f1", "by using human e2f1 construct", "human e2f1 construct arata", "e2f1 construct arata et", "construct arata et al.", "arata et al. 2000 .", "et al. 2000 . cyclin", "al. 2000 . cyclin e", "2000 . cyclin e is", ". cyclin e is also", "cyclin e is also transcriptionally", "e is also transcriptionally regulated", "is also transcriptionally regulated by", "also transcriptionally regulated by e2f1.", "transcriptionally regulated by e2f1. cyclin", "regulated by e2f1. cyclin e", "by e2f1. cyclin e protein", "e2f1. cyclin e protein plays", "cyclin e protein plays important", "e protein plays important role", "protein plays important role in", "plays important role in the", "important role in the transition", "role in the transition of", "in the transition of g1", "the transition of g1 in", "transition of g1 in s", "of g1 in s phase", "g1 in s phase by", "in s phase by associating", "s phase by associating with", "phase by associating with cdk2", "associating with cdk2 ohtani", "with cdk2 ohtani et", "cdk2 ohtani et al.", "ohtani et al. 1996 .", "et al. 1996 . e2f1", "al. 1996 . e2f1 mediated", "1996 . e2f1 mediated activation", ". e2f1 mediated activation of", "e2f1 mediated activation of pcna", "mediated activation of pcna has", "activation of pcna has been", "of pcna has been demonstrated", "pcna has been demonstrated in", "has been demonstrated in drosophila", "demonstrated in drosophila duronio", "and o'farrell 1994 and", "o'farrell 1994 and in", "1994 and in some", "and in some human cells", "in some human cells by", "some human cells by using", "human cells by using recombinant", "cells by using recombinant adenovirus", "by using recombinant adenovirus constructs", "recombinant adenovirus constructs degregori", "adenovirus constructs degregori et", "constructs degregori et al.", "degregori et al. 1995 .", "et al. 1995 . e2f1", "al. 1995 . e2f1 mediated", "1995 . e2f1 mediated activation", "e2f1 mediated activation of the", "mediated activation of the dna", "activation of the dna polymerase", "of the dna polymerase alpha", "the dna polymerase alpha subunit", "dna polymerase alpha subunit p180", "alpha subunit p180 pola1", "p180 pola1 has", "pola1 has been demonstrated", "has been demonstrated in some", "been demonstrated in some human", "demonstrated in some human cells.", "in some human cells. it", "some human cells. it has", "human cells. it has also", "cells. it has also been", "it has also been demonstrated", "has also been demonstrated in", "also been demonstrated in drosophila", "been demonstrated in drosophila by", "demonstrated in drosophila by ohtani", "in drosophila by ohtani and", "drosophila by ohtani and nevins", "ohtani and nevins 1994", "and nevins 1994 .", "nevins 1994 . it", "1994 . it has been", ". it has been observed", "it has been observed in", "has been observed in drosophila", "been observed in drosophila that", "observed in drosophila that e2f1", "in drosophila that e2f1 induced", "drosophila that e2f1 induced expression", "that e2f1 induced expression of", "e2f1 induced expression of orc1", "induced expression of orc1 stimulates", "expression of orc1 stimulates orc1", "of orc1 stimulates orc1 6", "orc1 stimulates orc1 6 complex", "stimulates orc1 6 complex formation", "orc1 6 complex formation and", "6 complex formation and binding", "complex formation and binding to", "formation and binding to the", "and binding to the origin", "binding to the origin of", "to the origin of replication", "origin of replication asano", "of replication asano and", "replication asano and wharton", "asano and wharton 1999 .", "and wharton 1999 . orc1", "wharton 1999 . orc1 6", "1999 . orc1 6 recruit", ". orc1 6 recruit cdc6", "orc1 6 recruit cdc6 and", "6 recruit cdc6 and cdt1", "recruit cdc6 and cdt1 that", "cdc6 and cdt1 that are", "and cdt1 that are required", "cdt1 that are required to", "that are required to recruit", "are required to recruit the", "required to recruit the mcm2", "to recruit the mcm2 7", "recruit the mcm2 7 replication", "the mcm2 7 replication helicases.", "mcm2 7 replication helicases. e2f1", "7 replication helicases. e2f1 regulation", "replication helicases. e2f1 regulation incorporates", "helicases. e2f1 regulation incorporates a", "e2f1 regulation incorporates a feedback", "regulation incorporates a feedback mechanism", "incorporates a feedback mechanism wherein", "a feedback mechanism wherein geminin", "mechanism wherein geminin gmnn", "geminin gmnn can", "gmnn can inhibit mcm2", "can inhibit mcm2 7 recruitment", 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              the p53 protein", "p53 protein.

              the p53 protein activates", "protein.

              the p53 protein activates the", "p53 protein activates the transcription", "protein activates the transcription of", "activates the transcription of cyclin", "the transcription of cyclin dependent", "transcription of cyclin dependent kinase", "of cyclin dependent kinase inhibitor", "dependent kinase inhibitor p21.", "kinase inhibitor p21. p21", "inhibitor p21. p21 inactivates", "p21. p21 inactivates the cycline:cdk2", "p21 inactivates the cycline:cdk2 complexes", "the cycline:cdk2 complexes and", "cycline:cdk2 complexes and prevent", "complexes and prevent entry", "and prevent entry of the", "prevent entry of the cell", "entry of the cell into", "of the cell into s", "the cell into s phase", "into s phase leading", "s phase leading to", "phase leading to g1", "to g1 arrest. under", "g1 arrest. under severe", "arrest. under severe conditions", "under severe conditions the", "severe conditions the cell", "conditions the cell may", "the cell may undergo apoptosis." ] }, { "record_id": "GLY_000594_1_1108", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "69656", "r hsa", "hsa 69656", "r hsa 69656" ] }, { "record_id": "GLY_000594_1_1108", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cyclin a:cdk2", "a:cdk2 associated", "associated events", "events at", "at s", "s phase", "phase entry", "cyclin a:cdk2 associated", "a:cdk2 associated events", "associated events at", "events at s", "at s phase", "s phase entry", "cyclin a:cdk2 associated events", "a:cdk2 associated events at", "associated events at s", "events at s phase", "at s phase entry", "cyclin a:cdk2 associated events at", "a:cdk2 associated events at s", "associated events at s phase", "events at s phase entry", "a:cdk2 plays", "plays a", "a key", "key role", "role in", "in s", "entry by", "by phosphorylation", "phosphorylation of", "of proteins", "proteins including", "including cdh1", "p21 and", "and p27.", "p27. during", "during g1", "g1 phase", "phase of", "of the", "the cell", "cell cycle", "cyclin a", "a is", "is synthesized", "synthesized and", "and associates", "associates with", "with cdk2.", "cdk2. after", "after forming", "forming in", "in the", "the cytoplasm", "the cyclin", "a:cdk2 complexes", "complexes are", "are translocated", "translocated to", "to the", "the nucleus", "jackman et", "et al.", "al. 2002", "2002 .", "prior to", "to s", "the activity", "activity of", "of cyclin", "complexes is", "is negatively", "negatively regulated", "regulated through", "through tyr", "tyr 15", "15 phosphorylation", "gu et", "and also", "also by", "by the", "the association", "association of", "cyclin kinase", "kinase inhibitors", "p27 and", "and p21.", "p21. phosphorylation", "cyclin dependent", "dependent kinases", "the cdk", "cdk activating", "activating kinase", "is required", "required for", "for the", "the activation", "activation of", "the cdk2", "cdk2 kinase", "kinase activity", "aprelikova et", "1995 .", ". the", "the entry", "entry into", "into s", "phase is", "is promoted", "promoted by", "the removal", "removal of", "of inhibitory", "inhibitory tyr", "15 phosphates", "phosphates from", "from the", "cdk2 subunit", "subunit of", "a:cdk2 complex", "complex by", "the cdc25", "cdc25 phosphatases", "blomberg and", "and hoffmann", "and by", "by scf", "scf skp2", "mediated degradation", "degradation of", "of p27/p21", "see ganoth", "ganoth et", "2001 .", ". while", "while cdk2", "cdk2 is", "is thought", "thought to", "to play", "play a", "a primary", "primary role", "in regulating", "regulating entry", "recent evidence", "evidence indicates", "indicates that", "that cdk1", "cdk1 is", "is equally", "equally capable", "capable of", "of promoting", "promoting entry", "phase and", "and the", "the initiation", "initiation of", "of dna", "dna replication", "bashir and", "and pagano", "2005 .", ". thus", "cdk1 complexes", "complexes may", "may also", "also play", "a significant", "significant role", "role at", "at this", "this point", "point in", "cell cycle.", "cyclin a:cdk2 plays", "a:cdk2 plays a", "plays a key", "a key role", "key role in", "role in s", "in s phase", "phase entry by", "entry by phosphorylation", "by phosphorylation of", "phosphorylation of proteins", "of proteins including", "proteins including cdh1", "cdh1 rb", "rb p21", "p21 and p27.", "and p27. during", "p27. during g1", "during g1 phase", "g1 phase of", "phase of the", "of the cell", "the cell cycle", "cycle cyclin", "cyclin a is", "a is synthesized", "is synthesized and", "synthesized and associates", "and associates with", "associates with cdk2.", "with cdk2. after", "cdk2. after forming", "after forming in", "forming in the", "in the cytoplasm", "cytoplasm the", "the cyclin a:cdk2", "cyclin a:cdk2 complexes", "a:cdk2 complexes are", "complexes are translocated", "are translocated to", "translocated to the", "to the nucleus", "nucleus jackman", "jackman et al.", "et al. 2002", "al. 2002 .", ". prior", "prior to s", "to s phase", "entry the", "the activity of", "activity of cyclin", "of cyclin a:cdk2", "a:cdk2 complexes is", "complexes is negatively", "is negatively regulated", "negatively regulated through", "regulated through tyr", "through tyr 15", "tyr 15 phosphorylation", "15 phosphorylation of", "of cdk2", "cdk2 gu", "gu et al.", "al. 1995", "1995 and", "and also by", "also by the", "by the association", "the association of", "association of the", "of the cyclin", "the cyclin kinase", "cyclin kinase inhibitors", "inhibitors ckis", "p27 and p21.", "and p21. phosphorylation", "p21. phosphorylation of", "phosphorylation of cyclin", "of cyclin dependent", "cyclin dependent kinases", "kinases cdks", "cdks by", "by the cdk", "the cdk activating", "cdk activating kinase", "kinase cak", "cak is", "is required for", "required for the", "for the activation", "the activation of", "activation of the", "of the cdk2", "the cdk2 kinase", "cdk2 kinase activity", "activity aprelikova", "aprelikova et al.", "1995 . the", ". the entry", "the entry into", "entry into s", "into s phase", "s phase is", "phase is promoted", "is promoted by", "promoted by the", "by the removal", "the removal of", "removal of inhibitory", "of inhibitory tyr", "inhibitory tyr 15", "tyr 15 phosphates", "15 phosphates from", "phosphates from the", "from the cdk2", "the cdk2 subunit", "cdk2 subunit of", "subunit of cyclin", "cyclin a:cdk2 complex", "a:cdk2 complex by", "complex by the", "by the cdc25", "the cdc25 phosphatases", "phosphatases blomberg", "blomberg and hoffmann", "hoffmann 1999", "1999 and", "and by scf", "by scf skp2", "skp2 mediated", "mediated degradation of", "degradation of p27/p21", "p27/p21 see", "see ganoth et", "ganoth et al.", "al. 2001", "2001 . while", ". while cdk2", "while cdk2 is", "cdk2 is thought", "is thought to", "thought to play", "to play a", "play a primary", "a primary role", "primary role in", "role in regulating", "in regulating entry", "regulating entry into", "phase recent", "recent evidence indicates", "evidence indicates that", "indicates that cdk1", "that cdk1 is", "cdk1 is equally", "is equally capable", "equally capable of", "capable of promoting", "of promoting entry", "promoting entry into", "s phase and", "phase and the", "and the initiation", "the initiation of", "initiation of dna", "of dna replication", "replication see", "see bashir", "bashir and pagano", "pagano 2005", "2005 . thus", "thus cdk1", "cdk1 complexes may", "complexes may also", "may also play", "also play a", "play a significant", "a significant role", "significant role at", "role at this", "at this point", "this point in", "point in the", "in the cell", "the cell cycle.", "cyclin a:cdk2 plays a", "a:cdk2 plays a key", "plays a key role", "a key role in", "key role in s", "role in s phase", "in s phase entry", "s phase entry by", "phase entry by phosphorylation", "entry by phosphorylation of", "by phosphorylation of proteins", "phosphorylation of proteins including", "of proteins including cdh1", "including cdh1 rb", "rb p21 and", "p21 and p27. during", "and p27. during g1", "p27. during g1 phase", "during g1 phase of", "g1 phase of the", "phase of the cell", "of the cell cycle", "cell cycle cyclin", "cycle cyclin a", "cyclin a is synthesized", "a is synthesized and", "is synthesized and associates", "synthesized and associates with", "and associates with cdk2.", "associates with cdk2. after", "with cdk2. after forming", "cdk2. after forming in", "after forming in the", "forming in the cytoplasm", "the cytoplasm the", "cytoplasm the cyclin", "the cyclin a:cdk2 complexes", "cyclin a:cdk2 complexes are", "a:cdk2 complexes are translocated", "complexes are translocated to", "are translocated to the", "translocated to the nucleus", "the nucleus jackman", "nucleus jackman et", "jackman et al. 2002", "et al. 2002 .", "2002 . prior", ". prior to", "prior to s phase", "to s phase entry", "phase entry the", "entry the activity", "the activity of cyclin", "activity of cyclin a:cdk2", "of cyclin a:cdk2 complexes", "cyclin a:cdk2 complexes is", "a:cdk2 complexes is negatively", "complexes is negatively regulated", "is negatively regulated through", "negatively regulated through tyr", "regulated through tyr 15", "through tyr 15 phosphorylation", "tyr 15 phosphorylation of", "phosphorylation of cdk2", "cdk2 gu et", "et al. 1995", "1995 and also", "and also by the", "also by the association", "by the association of", "the association of the", "association of the cyclin", "of the cyclin kinase", "the cyclin kinase inhibitors", "kinase inhibitors ckis", "ckis p27", "p27 and p21. phosphorylation", "and p21. phosphorylation of", "p21. phosphorylation of cyclin", "phosphorylation of cyclin dependent", "of cyclin dependent kinases", "dependent kinases cdks", "cdks by the", "by the cdk activating", "the cdk activating kinase", "activating kinase cak", "cak is required", "is required for the", "required for the activation", "for the activation of", "the activation of the", "activation of the cdk2", "of the cdk2 kinase", "the cdk2 kinase activity", "kinase activity aprelikova", "activity aprelikova et", "al. 1995 .", "1995 . the entry", ". the entry into", "the entry into s", "entry into s phase", "into s phase is", "s phase is promoted", "phase is promoted by", "is promoted by the", "promoted by the removal", "by the removal of", "the removal of inhibitory", "removal of inhibitory tyr", "of inhibitory tyr 15", "inhibitory tyr 15 phosphates", "tyr 15 phosphates from", "15 phosphates from the", "phosphates from the cdk2", "from the cdk2 subunit", "the cdk2 subunit of", "cdk2 subunit of cyclin", "subunit of cyclin a:cdk2", "of cyclin a:cdk2 complex", "cyclin a:cdk2 complex by", "a:cdk2 complex by the", "complex by the cdc25", "by the cdc25 phosphatases", "cdc25 phosphatases blomberg", "phosphatases blomberg and", "and hoffmann 1999", "1999 and by", "and by scf skp2", "scf skp2 mediated", "skp2 mediated degradation", "mediated degradation of p27/p21", "of p27/p21 see", "p27/p21 see ganoth", "see ganoth et al.", "et al. 2001", "al. 2001 .", "2001 . while cdk2", ". while cdk2 is", "while cdk2 is thought", "cdk2 is thought to", "is thought to play", "thought to play a", "to play a primary", "play a primary role", "a primary role in", "primary role in regulating", "role in regulating entry", "in regulating entry into", "regulating entry into s", "s phase recent", "phase recent evidence", "recent evidence indicates that", "evidence indicates that cdk1", "indicates that cdk1 is", "that cdk1 is equally", "cdk1 is equally capable", "is equally capable of", "equally capable of promoting", "capable of promoting entry", "of promoting entry into", "promoting entry into s", "into s phase and", "s phase and the", "phase and the initiation", "and the initiation of", "the initiation of dna", "initiation of dna replication", "dna replication see", "see bashir and", "and pagano 2005", "pagano 2005 .", ". thus cdk1", "thus cdk1 complexes", "cdk1 complexes may also", "complexes may also play", "may also play a", "also play a significant", "play a significant role", "a significant role at", "significant role at this", "role at this point", "at this point in", "this point in the", "point in the cell", "in the cell cycle.", "cyclin a:cdk2 plays a key", "a:cdk2 plays a key role", "plays a key role in", "a key role in s", "key role in s phase", "role in s phase entry", "in s phase entry by", "s phase entry by phosphorylation", "phase entry by phosphorylation of", "entry by phosphorylation of proteins", "by phosphorylation of proteins including", "phosphorylation of proteins including cdh1", "proteins including cdh1 rb", "cdh1 rb p21", "rb p21 and p27.", "p21 and p27. during g1", "and p27. during g1 phase", "p27. during g1 phase of", "during g1 phase of the", "g1 phase of the cell", "phase of the cell cycle", "the cell cycle cyclin", "cell cycle cyclin a", "cycle cyclin a is", "cyclin a is synthesized and", "a is synthesized and associates", "is synthesized and associates with", "synthesized and associates with cdk2.", "and associates with cdk2. after", "associates with cdk2. after forming", "with cdk2. after forming in", "cdk2. after forming in the", "after forming in the cytoplasm", "in the cytoplasm the", "the cytoplasm the cyclin", "cytoplasm the cyclin a:cdk2", "the cyclin a:cdk2 complexes are", "cyclin a:cdk2 complexes are translocated", "a:cdk2 complexes are translocated to", "complexes are translocated to the", "are translocated to the nucleus", "to the nucleus jackman", "the nucleus jackman et", "nucleus jackman et al.", "jackman et al. 2002 .", "al. 2002 . prior", "2002 . prior to", ". prior to s", "prior to s phase entry", "s phase entry the", "phase entry the activity", "entry the activity of", "the activity of cyclin a:cdk2", "activity of cyclin a:cdk2 complexes", "of cyclin a:cdk2 complexes is", "cyclin a:cdk2 complexes is negatively", "a:cdk2 complexes is negatively regulated", "complexes is negatively regulated through", "is negatively regulated through tyr", "negatively regulated through tyr 15", "regulated through tyr 15 phosphorylation", "through tyr 15 phosphorylation of", "15 phosphorylation of cdk2", "of cdk2 gu", "cdk2 gu et al.", "gu et al. 1995", "al. 1995 and", "1995 and also by", "and also by the association", "also by the association of", "by the association of the", "the association of the cyclin", "association of the cyclin kinase", "of the cyclin kinase inhibitors", "cyclin kinase inhibitors ckis", "ckis p27 and", "p27 and p21. phosphorylation of", "and p21. phosphorylation of cyclin", "p21. phosphorylation of cyclin dependent", "phosphorylation of cyclin dependent kinases", "cyclin dependent kinases cdks", "kinases cdks by", "cdks by the cdk", "by the cdk activating kinase", "cdk activating kinase cak", "kinase cak is", "cak is required for", "is required for the activation", "required for the activation of", "for the activation of the", "the activation of the cdk2", "activation of the cdk2 kinase", "of the cdk2 kinase activity", "cdk2 kinase activity aprelikova", "kinase activity aprelikova et", "activity aprelikova et al.", "aprelikova et al. 1995", "et al. 1995 .", "al. 1995 . the", "1995 . the entry into", ". the entry into s", "the entry into s phase", "entry into s phase is", "into s phase is promoted", "s phase is promoted by", "phase is promoted by the", "is promoted by the removal", "promoted by the removal of", "by the removal of inhibitory", "the removal of inhibitory tyr", "removal of inhibitory tyr 15", "of inhibitory tyr 15 phosphates", "inhibitory tyr 15 phosphates from", "tyr 15 phosphates from the", "15 phosphates from the cdk2", "phosphates from the cdk2 subunit", "from the cdk2 subunit of", "the cdk2 subunit of cyclin", "cdk2 subunit of cyclin a:cdk2", "subunit of cyclin a:cdk2 complex", "of cyclin a:cdk2 complex by", "cyclin a:cdk2 complex by the", "a:cdk2 complex by the cdc25", "complex by the cdc25 phosphatases", "the cdc25 phosphatases blomberg", "cdc25 phosphatases blomberg and", "phosphatases blomberg and hoffmann", "blomberg and hoffmann 1999", "hoffmann 1999 and", "1999 and by scf", "by scf skp2 mediated", "scf skp2 mediated degradation", "skp2 mediated degradation of", "degradation of p27/p21 see", "of p27/p21 see ganoth", "p27/p21 see ganoth et", "ganoth et al. 2001", "et al. 2001 .", "al. 2001 . while", "2001 . while cdk2 is", ". while cdk2 is thought", "while cdk2 is thought to", "cdk2 is thought to play", "is thought to play a", "thought to play a primary", "to play a primary role", "play a primary role in", "a primary role in regulating", "primary role in regulating entry", "role in regulating entry into", "in regulating entry into s", "regulating entry into s phase", "into s phase recent", "s phase recent evidence", "phase recent evidence indicates", "recent evidence indicates that cdk1", "evidence indicates that cdk1 is", "indicates that cdk1 is equally", "that cdk1 is equally capable", "cdk1 is equally capable of", "is equally capable of promoting", "equally capable of promoting entry", "capable of promoting entry into", "of promoting entry into s", "promoting entry into s phase", "entry into s phase and", "into s phase and the", "s phase and the initiation", "phase and the initiation of", "and the initiation of dna", "the initiation of dna replication", "of dna replication see", "replication see bashir", "see bashir and pagano", "bashir and pagano 2005", "and pagano 2005 .", "pagano 2005 . thus", "2005 . thus cdk1", ". thus cdk1 complexes", "thus cdk1 complexes may", "cdk1 complexes may also play", "complexes may also play a", "may also play a significant", "also play a significant role", "play a significant role at", "a significant role at this", "significant role at this point", "role at this point in", "at this point in the", "this point in the cell", "point in the cell cycle." ] }, { "record_id": "GLY_000594_1_1109", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "70350", "r hsa", "hsa 70350", "r hsa 70350" ] }, { "record_id": "GLY_000594_1_1109", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fructose catabolism", "fructose occurs", "occurs naturally", "naturally in", "in foods", "foods as", "as a", "a free", "free monosaccharide", "monosaccharide and", "and as", "a component", "component of", "of the", "the disaccharide", "disaccharide sucrose.", "sucrose. it", "it is", "is also", "also widely", "widely used", "used as", "a sweetener.", "sweetener. in", "in the", "the body", "catabolism occurs", "occurs in", "the liver", "liver and", "and to", "to a", "a lesser", "lesser extent", "extent in", "the kidney", "kidney and", "and small", "small intestine.", "intestine. in", "in these", "these tissues", "is converted", "converted to", "to dihydroxyacetone", "dihydroxyacetone phosphate", "phosphate and", "and d", "d glyceraldehyde", "glyceraldehyde 3", "3 phosphate", "two intermediates", "intermediates in", "the glycolytic", "glycolytic pathway", "in a", "a sequence", "sequence of", "of three", "three reactions.", "reactions. it", "is phosphorylated", "phosphorylated to", "to form", "form fructose", "fructose 1", "1 phosphate", "which is", "is cleaved", "cleaved by", "by aldolase", "aldolase to", "to yield", "yield dihydroxyacetone", "and the", "the latter", "latter compound", "compound is", "yield d", "3 phosphate.", "phosphate. other", "other pathways", "pathways exist", "exist for", "for the", "the conversion", "conversion of", "of d", "glyceraldehyde to", "to intermediates", "intermediates of", "of glycolysis", "but these", "these appear", "appear to", "to play", "play only", "only a", "a minor", "minor role", "role in", "in normal", "normal fructose", "fructose metabolism", "sillero et", "et al.", "al. 1969", "1969 .", "fructose occurs naturally", "occurs naturally in", "naturally in foods", "in foods as", "foods as a", "as a free", "a free monosaccharide", "free monosaccharide and", "monosaccharide and as", "and as a", "as a component", "a component of", "component of the", "of the disaccharide", "the disaccharide sucrose.", "disaccharide sucrose. it", "sucrose. it is", "it is also", "is also widely", "also widely used", "widely used as", "used as a", "as a sweetener.", "a sweetener. in", "sweetener. in the", "in the body", "body fructose", "fructose catabolism occurs", "catabolism occurs in", "occurs in the", "in the liver", "the liver and", "liver and to", "and to a", "to a lesser", "a lesser extent", "lesser extent in", "extent in the", "in the kidney", "the kidney and", "kidney and small", "and small intestine.", "small intestine. in", "intestine. in these", "in these tissues", "tissues it", "it is converted", "is converted to", "converted to dihydroxyacetone", "to dihydroxyacetone phosphate", "dihydroxyacetone phosphate and", "phosphate and d", "and d glyceraldehyde", "d glyceraldehyde 3", "glyceraldehyde 3 phosphate", "phosphate two", "two intermediates in", "intermediates in the", "in the glycolytic", "the glycolytic pathway", "pathway in", "in a sequence", "a sequence of", "sequence of three", "of three reactions.", "three reactions. it", "reactions. it is", "it is phosphorylated", "is phosphorylated to", "phosphorylated to form", "to form fructose", "form fructose 1", "fructose 1 phosphate", "phosphate which", "which is cleaved", "is cleaved by", "cleaved by aldolase", "by aldolase to", "aldolase to yield", "to yield dihydroxyacetone", "yield dihydroxyacetone phosphate", "glyceraldehyde and", "and the latter", "the latter compound", "latter compound is", "compound is phosphorylated", "phosphorylated to yield", "to yield d", "yield d glyceraldehyde", "glyceraldehyde 3 phosphate.", "3 phosphate. other", "phosphate. other pathways", "other pathways exist", "pathways exist for", "exist for the", "for the conversion", "the conversion of", "conversion of d", "of d glyceraldehyde", "d glyceraldehyde to", "glyceraldehyde to intermediates", "to intermediates of", "intermediates of glycolysis", "glycolysis but", "but these appear", "these appear to", "appear to play", "to play only", "play only a", "only a minor", "a minor role", "minor role in", "role in normal", "in normal fructose", "normal fructose metabolism", "metabolism sillero", "sillero et al.", "et al. 1969", "al. 1969 .", "fructose occurs naturally in", "occurs naturally in foods", "naturally in foods as", "in foods as a", "foods as a free", "as a free monosaccharide", "a free monosaccharide and", "free monosaccharide and as", "monosaccharide and as a", "and as a component", "as a component of", "a component of the", "component of the disaccharide", "of the disaccharide sucrose.", "the disaccharide sucrose. it", "disaccharide sucrose. it is", "sucrose. it is also", "it is also widely", "is also widely used", "also widely used as", "widely used as a", "used as a sweetener.", "as a sweetener. in", "a sweetener. in the", "sweetener. in the body", "the body fructose", "body fructose catabolism", "fructose catabolism occurs in", "catabolism occurs in the", "occurs in the liver", "in the liver and", "the liver and to", "liver and to a", "and to a lesser", "to a lesser extent", "a lesser extent in", "lesser extent in the", "extent in the kidney", "in the kidney and", "the kidney and small", "kidney and small intestine.", "and small intestine. in", "small intestine. in these", "intestine. in these tissues", "these tissues it", "tissues it is", "it is converted to", "is converted to dihydroxyacetone", "converted to dihydroxyacetone phosphate", "to dihydroxyacetone phosphate and", "dihydroxyacetone phosphate and d", "phosphate and d glyceraldehyde", "and d glyceraldehyde 3", "d glyceraldehyde 3 phosphate", "3 phosphate two", "phosphate two intermediates", "two intermediates in the", "intermediates in the glycolytic", "in the glycolytic pathway", "glycolytic pathway in", "pathway in a", "in a sequence of", "a sequence of three", "sequence of three reactions.", "of three reactions. it", "three reactions. it is", "reactions. it is phosphorylated", "it is phosphorylated to", "is phosphorylated to form", "phosphorylated to form fructose", "to form fructose 1", "form fructose 1 phosphate", "1 phosphate which", "phosphate which is", "which is cleaved by", "is cleaved by aldolase", "cleaved by aldolase to", "by aldolase to yield", "aldolase to yield dihydroxyacetone", "to yield dihydroxyacetone phosphate", "yield dihydroxyacetone phosphate and", "d glyceraldehyde and", "glyceraldehyde and the", "and the latter compound", "the latter compound is", "latter compound is phosphorylated", "compound is phosphorylated to", "is phosphorylated to yield", "phosphorylated to yield d", "to yield d glyceraldehyde", "yield d glyceraldehyde 3", "d glyceraldehyde 3 phosphate.", "glyceraldehyde 3 phosphate. other", "3 phosphate. other pathways", "phosphate. other pathways exist", "other pathways exist for", "pathways exist for the", "exist for the conversion", "for the conversion of", "the conversion of d", "conversion of d glyceraldehyde", "of d glyceraldehyde to", "d glyceraldehyde to intermediates", "glyceraldehyde to intermediates of", "to intermediates of glycolysis", "of glycolysis but", "glycolysis but these", "but these appear to", "these appear to play", "appear to play only", "to play only a", "play only a minor", "only a minor role", "a minor role in", "minor role in normal", "role in normal fructose", "in normal fructose metabolism", "fructose metabolism sillero", "metabolism sillero et", "sillero et al. 1969", "et al. 1969 .", "fructose occurs naturally in foods", "occurs naturally in foods as", "naturally in foods as a", "in foods as a free", "foods as a free monosaccharide", "as a free monosaccharide and", "a free monosaccharide and as", "free monosaccharide and as a", "monosaccharide and as a component", "and as a component of", "as a component of the", "a component of the disaccharide", "component of the disaccharide sucrose.", "of the disaccharide sucrose. it", "the disaccharide sucrose. it is", "disaccharide sucrose. it is also", "sucrose. it is also widely", "it is also widely used", "is also widely used as", "also widely used as a", "widely used as a sweetener.", "used as a sweetener. in", "as a sweetener. in the", "a sweetener. in the body", "in the body fructose", "the body fructose catabolism", "body fructose catabolism occurs", "fructose catabolism occurs in the", "catabolism occurs in the liver", "occurs in the liver and", "in the liver and to", "the liver and to a", "liver and to a lesser", "and to a lesser extent", "to a lesser extent in", "a lesser extent in the", "lesser extent in the kidney", "extent in the kidney and", "in the kidney and small", "the kidney and small intestine.", "kidney and small intestine. in", "and small intestine. in these", "small intestine. in these tissues", "in these tissues it", "these tissues it is", "tissues it is converted", "it is converted to dihydroxyacetone", "is converted to dihydroxyacetone phosphate", "converted to dihydroxyacetone phosphate and", "to dihydroxyacetone phosphate and d", "dihydroxyacetone phosphate and d glyceraldehyde", "phosphate and d glyceraldehyde 3", "and d glyceraldehyde 3 phosphate", "glyceraldehyde 3 phosphate two", "3 phosphate two intermediates", "phosphate two intermediates in", "two intermediates in the glycolytic", "intermediates in the glycolytic pathway", "the glycolytic pathway in", "glycolytic pathway in a", "pathway in a sequence", "in a sequence of three", "a sequence of three reactions.", "sequence of three reactions. it", "of three reactions. it is", "three reactions. it is phosphorylated", "reactions. it is phosphorylated to", "it is phosphorylated to form", "is phosphorylated to form fructose", "phosphorylated to form fructose 1", "to form fructose 1 phosphate", "fructose 1 phosphate which", "1 phosphate which is", "phosphate which is cleaved", "which is cleaved by aldolase", "is cleaved by aldolase to", "cleaved by aldolase to yield", "by aldolase to yield dihydroxyacetone", "aldolase to yield dihydroxyacetone phosphate", "to yield dihydroxyacetone phosphate and", "yield dihydroxyacetone phosphate and d", "and d glyceraldehyde and", "d glyceraldehyde and the", "glyceraldehyde and the latter", "and the latter compound is", "the latter compound is phosphorylated", "latter compound is phosphorylated to", "compound is phosphorylated to yield", "is phosphorylated to yield d", "phosphorylated to yield d glyceraldehyde", "to yield d glyceraldehyde 3", "yield d glyceraldehyde 3 phosphate.", "d glyceraldehyde 3 phosphate. other", "glyceraldehyde 3 phosphate. other pathways", "3 phosphate. other pathways exist", "phosphate. other pathways exist for", "other pathways exist for the", "pathways exist for the conversion", "exist for the conversion of", "for the conversion of d", "the conversion of d glyceraldehyde", "conversion of d glyceraldehyde to", "of d glyceraldehyde to intermediates", "d glyceraldehyde to intermediates of", "glyceraldehyde to intermediates of glycolysis", "intermediates of glycolysis but", "of glycolysis but these", "glycolysis but these appear", "but these appear to play", "these appear to play only", "appear to play only a", "to play only a minor", "play only a minor role", "only a minor role in", "a minor role in normal", "minor role in normal fructose", "role in normal fructose metabolism", "normal fructose metabolism sillero", "fructose metabolism sillero et", "metabolism sillero et al.", "sillero et al. 1969 ." ] }, { "record_id": "GLY_000594_1_1110", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "70635", "r hsa", "hsa 70635", "r hsa 70635" ] }, { "record_id": "GLY_000594_1_1110", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "urea cycle", "the urea", "cycle yields", "yields urea", "the major", "major form", "form in", "in which", "which excess", "excess nitrogen", "nitrogen is", "is excreted", "excreted from", "from the", "the human", "human body", "and the", "the amino", "amino acid", "acid arginine", "brusilow and", "and horwich", "horwich 2001", "2001 .", ". it", "it consists", "consists of", "of four", "four reactions:", "reactions: that", "that of", "of ornithine", "ornithine and", "and carbamoyl", "carbamoyl phosphate", "phosphate to", "to form", "form citrulline", "of citrulline", "citrulline and", "and aspartate", "aspartate to", "form argininosuccinate", "the cleavage", "cleavage of", "of argininosuccinate", "argininosuccinate to", "to yield", "yield fumarate", "fumarate and", "and arginine", "of arginine", "arginine to", "yield urea", "urea and", "and re", "re form", "form ornithine.", "ornithine. the", "the carbamoyl", "phosphate consumed", "consumed in", "in 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              two", "synthesis.

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              two", "urea synthesis.

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              two", "stimulate urea synthesis.

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"body and the amino", "and the amino acid arginine", "amino acid arginine brusilow", "acid arginine brusilow and", "arginine brusilow and horwich", "brusilow and horwich 2001 .", "and horwich 2001 . it", "horwich 2001 . it consists", "2001 . it consists of", ". it consists of four", "it consists of four reactions:", "consists of four reactions: that", "of four reactions: that of", "four reactions: that of ornithine", "reactions: that of ornithine and", "that of ornithine and carbamoyl", "of ornithine and carbamoyl phosphate", "ornithine and carbamoyl phosphate to", "and carbamoyl phosphate to form", "carbamoyl phosphate to form citrulline", "to form citrulline of", "form citrulline of citrulline", "citrulline of citrulline and", "of citrulline and aspartate to", "citrulline and aspartate to form", "and aspartate to form argininosuccinate", "to form argininosuccinate the", "form argininosuccinate the cleavage", "argininosuccinate the cleavage of", "the cleavage of argininosuccinate to", "cleavage of argininosuccinate to yield", "of argininosuccinate to yield fumarate", "argininosuccinate to yield fumarate and", "to yield fumarate and arginine", "fumarate and arginine and", "and arginine and the", "arginine and the cleavage", "and the cleavage of arginine", "the cleavage of arginine to", "cleavage of arginine to yield", "of arginine to yield urea", "arginine to yield urea and", "to yield urea and re", "yield urea and re form", "urea and re form ornithine.", "and re form ornithine. the", "re form ornithine. the carbamoyl", "form ornithine. the carbamoyl phosphate", "ornithine. the carbamoyl phosphate consumed", "the carbamoyl phosphate consumed in", "carbamoyl phosphate consumed in this", "phosphate consumed in this cycle", "consumed in this cycle is", "in this cycle is synthesized", "this cycle is synthesized in", "cycle is synthesized in the", "is synthesized in the mitochondria", "synthesized in the mitochondria from", "in the mitochondria from bicarbonate", "the mitochondria from bicarbonate and", "mitochondria from bicarbonate and ammonia", "bicarbonate and ammonia and", "and ammonia and this", "ammonia and this synthesis", "and this synthesis in turn", "this synthesis in turn is", "synthesis in turn is dependent", "in turn is dependent on", "turn is dependent on the", "is dependent on the presence", "dependent on the presence of", "on the presence of n", "the presence of n acetylglutamate", "of n acetylglutamate which", "n acetylglutamate which allosterically", "acetylglutamate which allosterically activates", "which allosterically activates carbamoyl synthetase", "allosterically activates carbamoyl synthetase i", "activates carbamoyl synthetase i enzyme.", "carbamoyl synthetase i enzyme. the", "synthetase i enzyme. the synthesis", "i enzyme. the synthesis of", "enzyme. the synthesis of n", "the synthesis of n acetylglutamate", "synthesis of n acetylglutamate is", "of n acetylglutamate is stimulated", "n acetylglutamate is stimulated by", "acetylglutamate is stimulated by high", "is stimulated by high levels", "stimulated by high levels of", "by high levels of arginine.", "high levels of arginine. increased", "levels of arginine. increased levels", "of arginine. increased levels of", "arginine. increased levels of free", "increased levels of free amino", "levels of free amino acids", "free amino acids indicated", "amino acids indicated by", "acids indicated by elevated", "indicated by elevated arginine levels", "elevated arginine levels thus", "arginine levels thus stimulate", "levels thus stimulate urea", "thus stimulate urea synthesis.

              two enzymes", "stimulate urea synthesis.

              two enzymes catalyze", "urea synthesis.

              two enzymes catalyze the", "synthesis.

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"from arginine and may have", "arginine and may have a", "and may have a substantial", "may have a substantial sparing", "have a substantial sparing effect", "a substantial sparing effect in", "substantial sparing effect in patients", "sparing effect in patients lacking", "effect in patients lacking arg1", "in patients lacking arg1 enzyme", "lacking arg1 enzyme so", "arg1 enzyme so its", "enzyme so its reaction", "so its reaction is annotated", "its reaction is annotated here", "reaction is annotated here although", "is annotated here although the", "annotated here although the role", "here although the role of", "although the role of arg2", "the role of arg2 under", "role of arg2 under normal", "of arg2 under normal physiological", "arg2 under normal physiological conditions", "under normal physiological conditions remains", "normal physiological conditions remains unclear." ] }, { "record_id": "GLY_000594_1_1111", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "70688", "r hsa", "hsa 70688", "r hsa 70688" ] }, { "record_id": "GLY_000594_1_1111", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "proline catabolism", "proline is", "is catabolized", "catabolized in", "in two", "two steps", "steps to", "to yield", "yield l", "l glutamate", "glutamate gamma", "gamma semialdehyde", "which can", "can react", "react further", "further with", "with glutamate", "glutamate to", "yield ornithine", "ornithine and", "and alpha", "alpha ketoglutarate", "annotated as", "as a", "a reaction", "reaction of", "of amino", "amino acid", "acid synthesis", "synthesis and", "and interconversion", "or with", "with nad+", "nad+ to", "yield glutamate", "glutamate and", "and nadh", "nadh +", "+ h+", "phang et", "et al.", "al. 2001", "2001 .", "proline is catabolized", "is catabolized in", "catabolized in two", "in two steps", "two steps to", "steps to yield", "to yield l", "yield l glutamate", "l 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nadh + h+", "nadh + h+ phang", "+ h+ phang et", "h+ phang et al.", "phang et al. 2001 ." ] }, { "record_id": "GLY_000594_1_1112", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71262", "r hsa", "hsa 71262", "r hsa 71262" ] }, { "record_id": "GLY_000594_1_1112", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "carnitine synthesis", "carnitine is", "is required", "required for", "for the", "the shuttling", "shuttling of", "of fatty", "fatty acids", "acids into", "into the", "the mitochondrial", "mitochondrial matrix", "matrix and", "and its", "its deficiency", "deficiency is", "is associated", "associated with", "with metabolic", "metabolic diseases.", "diseases. it", "it is", "is abundant", "abundant in", "in a", "a typical", "typical western", "western diet", "diet but", "but can", "can also", "also be", "be synthesized", "synthesized in", "in four", "four steps", "steps from", "from 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western", "typical western diet", "western diet but", "diet but can", "but can also", "can also be", "also be synthesized", "be synthesized in", "synthesized in four", "in four steps", "four steps from", "steps from trimethyllysine", "trimethyllysine generated", "generated in turn", "in turn by", "turn by the", "by the s", "the s adenosyl", "s adenosyl methionine", "adenosyl methionine mediated", "methionine mediated methylation", "mediated methylation of", "methylation of lysine", "of lysine residues", "lysine residues in", "residues in proteins", "proteins followed", "followed by protein", "by protein hydrolysis", "protein hydrolysis .", "hydrolysis . the", ". the enzymes", "the enzymes that", "enzymes that catalyze", "that catalyze the", "catalyze the first", "the first three", "first three steps", "three steps of", "steps of carnitine", "of carnitine synthesis", "synthesis converting", "converting trimethyllysine to", "trimethyllysine to gamma", "to gamma butyrobetaine", "butyrobetaine are", "are widely distributed", "widely distributed in", "distributed in human", "in human tissues.", "human tissues. the", "tissues. the enzyme", "the enzyme that", "enzyme that catalyzes", "that catalyzes the", "catalyzes the last", "the last reaction", "reaction converting", "converting gamma butyrobetaine", "gamma butyrobetaine to", "butyrobetaine to carnitine", "is found only", "found only in", "only in liver", "in liver and", "liver and kidney", "and kidney cells", "cells and", "and at very", "at very low", "very low levels", "low levels in", "levels in brain", "in brain tissues.", "brain tissues. other", "tissues. other tissues", "other tissues that", "tissues that require", "that require carnitine", "carnitine such", "such as muscle", "muscle are", "are dependent on", "dependent on transport", "on transport systems", "transport systems that", "systems that mediate", "that mediate its", "mediate its export", "its export from", "export from the", "from the liver", "the liver and", "liver and uptake", "and uptake by", "uptake by other", "by other tissues", "tissues bremer", "1983 kerner", "kerner & hoppel", "& hoppel 1998", "1998 rebouche", "rebouche & engel", "& engel 1980", "1980 vaz", "vaz & wanders", "& wanders 2002", "wanders 2002 .", "carnitine is required for", "is required for the", "required for the shuttling", "for the shuttling of", "the shuttling of fatty", "shuttling of fatty acids", "of fatty acids into", "fatty acids into the", "acids into the mitochondrial", "into the mitochondrial matrix", "the mitochondrial matrix and", "mitochondrial matrix and its", "matrix and its deficiency", "and its deficiency is", "its deficiency is associated", "deficiency is associated with", "is associated with metabolic", "associated with metabolic diseases.", "with metabolic diseases. it", "metabolic diseases. it is", "diseases. it is abundant", "it is abundant in", "is abundant in a", "abundant in a typical", "in a typical western", "a typical western diet", "typical western diet but", "western diet but can", "diet but can also", "but can also be", "can also be synthesized", "also be synthesized in", "be synthesized in four", "synthesized in four steps", "in four steps from", "four steps from trimethyllysine", "from trimethyllysine generated", "trimethyllysine generated in", "generated in turn by", "in turn by the", "turn by the s", "by the s adenosyl", "the s adenosyl methionine", "s adenosyl methionine mediated", "adenosyl methionine mediated methylation", "methionine mediated methylation of", "mediated methylation of lysine", "methylation of lysine residues", "of lysine residues in", "lysine residues in proteins", "in proteins followed", "proteins followed by", "followed by protein hydrolysis", "by protein hydrolysis .", "protein hydrolysis . the", "hydrolysis . the enzymes", ". the enzymes that", "the enzymes that catalyze", "enzymes that catalyze the", "that catalyze the first", "catalyze the first three", "the first three steps", "first three steps of", "three steps of carnitine", "steps of carnitine synthesis", "carnitine synthesis converting", "synthesis converting trimethyllysine", "converting trimethyllysine to gamma", "trimethyllysine to gamma butyrobetaine", "gamma butyrobetaine are", "butyrobetaine are widely", "are widely distributed in", "widely distributed in human", "distributed in human tissues.", "in human tissues. the", "human tissues. the enzyme", "tissues. the enzyme that", "the enzyme that catalyzes", "enzyme that catalyzes the", "that catalyzes the last", "catalyzes the last reaction", "last reaction converting", "reaction converting gamma", "converting gamma butyrobetaine to", "gamma butyrobetaine to carnitine", "to carnitine is", "carnitine is found", "is found only in", "found only in liver", "only in liver and", "in liver and kidney", "liver and kidney cells", "kidney cells and", "cells and at", "and at very low", "at very low levels", "very low levels in", "low levels in brain", "levels in brain tissues.", "in brain tissues. other", "brain tissues. other tissues", "tissues. other tissues that", "other tissues that require", "tissues that require carnitine", "require carnitine such", "carnitine such as", "as muscle are", "muscle are dependent", "are dependent on transport", "dependent on transport systems", "on transport systems that", "transport systems that mediate", "systems that mediate its", "that mediate its export", "mediate its export from", "its export from the", "export from the liver", "from the liver and", "the liver and uptake", "liver and uptake by", "and uptake by other", "uptake by other tissues", "other tissues bremer", "tissues bremer 1983", "bremer 1983 kerner", "1983 kerner &", "kerner & hoppel 1998", "hoppel 1998 rebouche", "1998 rebouche &", "rebouche & engel 1980", "engel 1980 vaz", "1980 vaz &", "vaz & wanders 2002", "& wanders 2002 .", "carnitine is required for the", "is required for the shuttling", "required for the shuttling of", "for the shuttling of fatty", "the shuttling of fatty acids", "shuttling of fatty acids into", "of fatty acids into the", "fatty acids into the mitochondrial", "acids into the mitochondrial matrix", "into the mitochondrial matrix and", "the mitochondrial matrix and its", "mitochondrial matrix and its deficiency", "matrix and its deficiency is", "and its deficiency is associated", "its deficiency is associated with", "deficiency is associated with metabolic", "is associated with metabolic diseases.", "associated with metabolic diseases. it", "with metabolic diseases. it is", "metabolic diseases. it is abundant", "diseases. it is abundant in", "it is abundant in a", "is abundant in a typical", "abundant in a typical western", "in a typical western diet", "a typical western diet but", "typical western diet but can", "western diet but can also", "diet but can also be", "but can also be synthesized", "can also be synthesized in", "also be synthesized in four", "be synthesized in four steps", "synthesized in four steps from", "in four steps from trimethyllysine", "steps from trimethyllysine generated", "from trimethyllysine generated in", "trimethyllysine generated in turn", "generated in turn by the", "in turn by the s", "turn by the s adenosyl", "by the s adenosyl methionine", "the s adenosyl methionine mediated", "s adenosyl methionine mediated methylation", "adenosyl methionine mediated methylation of", "methionine mediated methylation of lysine", "mediated methylation of lysine residues", "methylation of lysine residues in", "of lysine residues in proteins", "residues in proteins followed", "in proteins followed by", "proteins followed by protein", "followed by protein hydrolysis .", "by protein hydrolysis . the", "protein hydrolysis . the enzymes", "hydrolysis . the enzymes that", ". the enzymes that catalyze", "the enzymes that catalyze the", "enzymes that catalyze the first", "that catalyze the first three", "catalyze the first three steps", "the first three steps of", "first three steps of carnitine", "three steps of carnitine synthesis", "of carnitine synthesis converting", "carnitine synthesis converting trimethyllysine", "synthesis converting trimethyllysine to", "converting trimethyllysine to gamma butyrobetaine", "to gamma butyrobetaine are", "gamma butyrobetaine are widely", "butyrobetaine are widely distributed", "are widely distributed in human", "widely distributed in human tissues.", "distributed in human tissues. the", "in human tissues. the enzyme", "human tissues. the enzyme that", "tissues. the enzyme that catalyzes", "the enzyme that catalyzes the", "enzyme that catalyzes the last", "that catalyzes the last reaction", "the last reaction converting", "last reaction converting gamma", "reaction converting gamma butyrobetaine", "converting gamma butyrobetaine to carnitine", "butyrobetaine to carnitine is", "to carnitine is found", "carnitine is found only", "is found only in liver", "found only in liver and", "only in liver and kidney", "in liver and kidney cells", "and kidney cells and", "kidney cells and at", "cells and at very", "and at very low levels", "at very low levels in", "very low levels in brain", "low levels in brain tissues.", "levels in brain tissues. other", "in brain tissues. other tissues", "brain tissues. other tissues that", "tissues. other tissues that require", "other tissues that require carnitine", "that require carnitine such", "require carnitine such as", "carnitine such as muscle", "such as muscle are", "as muscle are dependent", "muscle are dependent on", "are dependent on transport systems", "dependent on transport systems that", "on transport systems that mediate", "transport systems that mediate its", "systems that mediate its export", "that mediate its export from", "mediate its export from the", "its export from the liver", "export from the liver and", "from the liver and uptake", "the liver and uptake by", "liver and uptake by other", "and uptake by other tissues", "by other tissues bremer", "other tissues bremer 1983", "bremer 1983 kerner &", "1983 kerner & hoppel", "& hoppel 1998 rebouche", "hoppel 1998 rebouche &", "1998 rebouche & engel", "& engel 1980 vaz", "engel 1980 vaz &", "1980 vaz & wanders", "vaz & wanders 2002 ." ] }, { "record_id": "GLY_000594_1_1113", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71336", "r hsa", "hsa 71336", "r hsa 71336" ] }, { "record_id": "GLY_000594_1_1113", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pentose phosphate", "phosphate pathway", "pentose phosphate pathway", "the pentose", "pathway is", "is responsible", "responsible for", "for the", "the generation", "generation of", "of a", "a substantial", "substantial fraction", "fraction of", "of the", "the cytoplasmic", "cytoplasmic nadph", "nadph required", "required for", "for biosynthetic", "biosynthetic reactions", "and for", "of ribose", "ribose 5", "5 phosphate", "phosphate for", "for nucleotide", "nucleotide synthesis.", "synthesis. although", "although the", "pathway and", "and glycolysis", "glycolysis are", "are distinct", "they involve", "involve three", "three common", "common intermediates", "glucose 6", "6 phosphate", "glyceraldehyde 3", "3 phosphate", "and fructose", "fructose 6", "so the", "the two", "two pathways", "pathways are", "are interconnected.", "interconnected. the", "pathway consists", "consists of", "of eight", "eight reactions:1.", "reactions:1. conversion", "conversion glucose", "phosphate to", "to d", "d glucono", "glucono 1", "1 5", "5 lactone", "lactone 6", "with the", "the formation", "formation of", "of nadph", "2. conversion", "conversion of", "of d", "to 6", "6 phospho", "phospho d", "d gluconate", "3. conversion", "of 6", "gluconate to", "to ribulose", "ribulose 5", "4. conversion", "of ribulose", "to xylulose", "xylulose 5", "5. conversion", "to ribose", "6. rearrangement", "rearrangement of", "phosphate and", "and xylulose", "to form", "form sedoheptulose", "sedoheptulose 7", "7 phosphate", "and glyceraldehyde", "7. rearrangement", "of sedoheptulose", "form erythrose", "4 phosphate", "and 8.", "8. rearrangement", "of xylulose", "and erythrose", "erythrose 4", "form glyceraldehyde", "6 phosphate.

              the", "phosphate.

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              the", "sugars.

              the overall", "overall pathway", "pathway can", "can operate", "operate to", "to generate", "generate only", "only nadph", "phosphate is", "is converted", "converted to", "to pentose", "5 phosphates", "which are", "are directed", "directed to", "to the", "the synthesis", "synthesis of", "of fructose", "which in", "in turn", "turn are", "are converted", "converted back", "back to", "to glucose", "phosphate .", ". the", "the reactions", "reactions of", "branch can", "generate net", "net amounts", "amounts of", "phosphate with", "with no", "no production", "production of", "of nadph.", "net flux", "flux through", "through this", "this network", "network of", "of reactions", "reactions appears", "appears to", "to depend", "depend on", "on the", "the metabolic", "metabolic state", "state of", "the cell", "cell and", "and the", "the nature", "nature of", "the biosynthetic", "reactions underway", "casazza and", "and veech", "veech 1987", "1987 .

              g6pd", "the enzyme", "enzyme that", "that catalyzes", "catalyzes the", "the first", "first reaction", "reaction of", "is more", "more extensively", "extensively mutated", "mutated in", "in human", "human populations", "populations than", "than any", "any other", "other enzyme", "pehaps because", "because these", "these mutant", "mutant alleles", "alleles confer", "confer malaria", "malaria resistance", "luzzatto and", "and afolayan", "afolayan 1968", "1968 .", ". mutations", "mutations affecting", "affecting other", "other parts", "parts of", "pathway are", "are rare", "though several", "several have", "have been", "been described", "described and", "and studies", "studies of", "of their", "their effects", "effects have", "have contributed", "contributed to", "to our", "our understanding", "understanding of", "the normal", "normal flux", "flux of", "of metabolites", "metabolites through", "wamelink et", "et al.", "al. 2008", "2008 .", "the pentose phosphate", "phosphate pathway is", "pathway is responsible", "is responsible for", "responsible for the", "for the generation", "the generation of", "generation of a", "of a substantial", "a substantial fraction", "substantial fraction of", "fraction of the", "of the cytoplasmic", "the cytoplasmic nadph", "cytoplasmic nadph required", "nadph required for", "required for biosynthetic", "for biosynthetic reactions", "reactions and", "and for the", "generation of ribose", "of ribose 5", "ribose 5 phosphate", "5 phosphate for", "phosphate for nucleotide", "for nucleotide synthesis.", "nucleotide synthesis. although", "synthesis. although the", "although the pentose", "phosphate pathway and", "pathway and glycolysis", "and glycolysis are", "glycolysis are distinct", "distinct they", "they involve three", "involve three common", "three common intermediates", "intermediates glucose", "glucose 6 phosphate", "phosphate glyceraldehyde", "glyceraldehyde 3 phosphate", "and fructose 6", "fructose 6 phosphate", "phosphate so", "so the two", "the two pathways", "two pathways are", "pathways are interconnected.", "are interconnected. the", "interconnected. the pentose", "phosphate pathway consists", "pathway consists of", "consists of eight", "of eight reactions:1.", "eight reactions:1. conversion", "reactions:1. conversion glucose", "conversion glucose 6", "6 phosphate to", "phosphate to d", "to d glucono", "d glucono 1", "glucono 1 5", "1 5 lactone", "5 lactone 6", "lactone 6 phosphate", "with the formation", "the formation of", "formation of nadph", "nadph 2.", "2. conversion of", "conversion of d", "of d glucono", "phosphate to 6", "to 6 phospho", "6 phospho d", "phospho d gluconate", "gluconate 3.", "3. conversion of", "conversion of 6", "of 6 phospho", "d gluconate to", "gluconate to ribulose", "to ribulose 5", "ribulose 5 phosphate", "nadph 4.", "4. conversion of", "conversion of ribulose", "of ribulose 5", "5 phosphate to", "phosphate to xylulose", "to xylulose 5", "xylulose 5 phosphate", "phosphate 5.", "5. conversion of", "phosphate to ribose", "to ribose 5", "phosphate 6.", "6. rearrangement of", "rearrangement of ribose", "5 phosphate and", "phosphate and xylulose", "and xylulose 5", "phosphate to form", "to form sedoheptulose", "form sedoheptulose 7", "sedoheptulose 7 phosphate", "7 phosphate and", "phosphate and glyceraldehyde", "and glyceraldehyde 3", "phosphate 7.", "7. rearrangement of", "rearrangement of sedoheptulose", "of sedoheptulose 7", "3 phosphate to", "to form erythrose", "4 phosphate and", "phosphate and fructose", "and 8. rearrangement", "8. rearrangement of", "rearrangement of xylulose", "of xylulose 5", "phosphate and erythrose", "and erythrose 4", "erythrose 4 phosphate", "4 phosphate to", "to form glyceraldehyde", "form glyceraldehyde 3", "3 phosphate and", "fructose 6 phosphate.

              the", "6 phosphate.

              the oxidative", "phosphate.

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              the", "other sugars.

              the overall", "sugars.

              the overall pathway", "overall pathway can", "pathway can operate", "can operate to", "operate to generate", "to generate only", "generate only nadph", "nadph glucose", "6 phosphate is", "phosphate is converted", "is converted to", "converted to pentose", "to pentose 5", "pentose 5 phosphates", "phosphates which", "which are directed", "are directed to", "directed to the", "to the synthesis", "the synthesis of", "synthesis of fructose", "of fructose 6", "6 phosphate and", "phosphate which", "which in turn", "in turn are", "turn are converted", "are converted back", "converted back to", "back to glucose", "to glucose 6", "6 phosphate .", "phosphate . the", ". the reactions", "the reactions of", "reactions of the", "of the non", "oxidative branch can", "branch can operate", "to generate net", "generate net amounts", "net amounts of", "amounts of ribose", "5 phosphate with", "phosphate with no", "with no production", "no production of", "production of nadph.", "nadph. net", "net flux through", "flux through this", "through this network", "this network of", "network of reactions", "of reactions appears", "reactions appears to", "appears to depend", "to depend on", "depend on the", "on the metabolic", "the metabolic state", "metabolic state of", "state of the", "of the cell", "the cell and", "cell and the", "and the nature", "the nature of", "nature of the", "of the biosynthetic", "the biosynthetic reactions", "biosynthetic reactions underway", "underway casazza", "casazza and veech", "and veech 1987", "veech 1987 .

              g6pd", ".

              g6pd the", "the enzyme that", "enzyme that catalyzes", "that catalyzes the", "catalyzes the first", "the first reaction", "first reaction of", "reaction of the", "is more extensively", "more extensively mutated", "extensively mutated in", "mutated in human", "in human populations", "human populations than", "populations than any", "than any other", "any other enzyme", "enzyme pehaps", "pehaps because these", "because these mutant", "these mutant alleles", "mutant alleles confer", "alleles confer malaria", "confer malaria resistance", "resistance luzzatto", "luzzatto and afolayan", "and afolayan 1968", "afolayan 1968 .", "1968 . mutations", ". mutations affecting", "mutations affecting other", "affecting other parts", "other parts of", "parts of the", "the pathway are", "pathway are rare", "rare though", "though several have", "several have been", "have been described", "been described and", "described and studies", "and studies of", "studies of their", "of their effects", "their effects have", "effects have contributed", "have contributed to", "contributed to our", "to our understanding", "our understanding of", "understanding of the", "of the normal", "the normal flux", "normal flux of", "flux of metabolites", "of metabolites through", "metabolites through this", "reactions wamelink", "wamelink et al.", "et al. 2008", "al. 2008 .", "the pentose phosphate pathway", "pentose phosphate pathway is", "phosphate pathway is responsible", "pathway is responsible for", "is responsible for the", "responsible for the generation", "for the generation of", "the generation of a", "generation of a substantial", "of a substantial fraction", "a substantial fraction of", "substantial fraction of the", "fraction of the cytoplasmic", "of the cytoplasmic nadph", "the cytoplasmic nadph required", "cytoplasmic nadph required for", "nadph required for biosynthetic", "required for biosynthetic reactions", "biosynthetic reactions and", "reactions and for", "and for the generation", "the generation of ribose", "generation of ribose 5", "of ribose 5 phosphate", "ribose 5 phosphate for", "5 phosphate for nucleotide", "phosphate for nucleotide synthesis.", "for nucleotide synthesis. although", "nucleotide synthesis. although the", "synthesis. although the pentose", "although the pentose phosphate", "pentose phosphate pathway and", "phosphate pathway and glycolysis", "pathway and glycolysis are", "and glycolysis are distinct", "are distinct they", "distinct they involve", "they involve three common", "involve three common intermediates", "common intermediates glucose", "intermediates glucose 6", "6 phosphate glyceraldehyde", "phosphate glyceraldehyde 3", "and fructose 6 phosphate", "6 phosphate so", "phosphate so the", "so the two pathways", "the two pathways are", "two pathways are interconnected.", "pathways are interconnected. the", "are interconnected. the pentose", "interconnected. the pentose phosphate", "pentose phosphate pathway consists", "phosphate pathway consists of", "pathway consists of eight", "consists of eight reactions:1.", "of eight reactions:1. conversion", "eight reactions:1. conversion glucose", "reactions:1. conversion glucose 6", "conversion glucose 6 phosphate", "glucose 6 phosphate to", "6 phosphate to d", "phosphate to d glucono", "to d glucono 1", "d glucono 1 5", "glucono 1 5 lactone", "1 5 lactone 6", "5 lactone 6 phosphate", "6 phosphate with", "phosphate with the", "with the formation of", "the formation of nadph", "of nadph 2.", "nadph 2. conversion", "2. conversion of d", "conversion of d glucono", "of d glucono 1", "lactone 6 phosphate to", "6 phosphate to 6", "phosphate to 6 phospho", "to 6 phospho d", "6 phospho d gluconate", "d gluconate 3.", "gluconate 3. conversion", "3. conversion of 6", "conversion of 6 phospho", "of 6 phospho d", "phospho d gluconate to", "d gluconate to ribulose", "gluconate to ribulose 5", "to ribulose 5 phosphate", "of nadph 4.", "nadph 4. conversion", "4. conversion of ribulose", "conversion of ribulose 5", "of ribulose 5 phosphate", "ribulose 5 phosphate to", "5 phosphate to xylulose", "phosphate to xylulose 5", "to xylulose 5 phosphate", "5 phosphate 5.", "phosphate 5. conversion", "5. conversion of ribulose", "5 phosphate to ribose", "phosphate to ribose 5", "to ribose 5 phosphate", "5 phosphate 6.", "phosphate 6. rearrangement", "6. rearrangement of ribose", "rearrangement of ribose 5", "ribose 5 phosphate and", "5 phosphate and xylulose", "phosphate and xylulose 5", "and xylulose 5 phosphate", "xylulose 5 phosphate to", "5 phosphate to form", "phosphate to form sedoheptulose", "to form sedoheptulose 7", "form sedoheptulose 7 phosphate", "sedoheptulose 7 phosphate and", "7 phosphate and glyceraldehyde", "phosphate and glyceraldehyde 3", "and glyceraldehyde 3 phosphate", "3 phosphate 7.", "phosphate 7. rearrangement", "7. rearrangement of sedoheptulose", "rearrangement of sedoheptulose 7", "of sedoheptulose 7 phosphate", "glyceraldehyde 3 phosphate to", "3 phosphate to form", "phosphate to form erythrose", "form erythrose 4", "4 phosphate and fructose", "phosphate and fructose 6", "phosphate and 8.", "and 8. rearrangement of", "8. rearrangement of xylulose", "rearrangement of xylulose 5", "of xylulose 5 phosphate", "xylulose 5 phosphate and", "5 phosphate and erythrose", "phosphate and erythrose 4", "and erythrose 4 phosphate", "erythrose 4 phosphate to", "4 phosphate to form", "phosphate to form glyceraldehyde", "to form glyceraldehyde 3", "form glyceraldehyde 3 phosphate", "glyceraldehyde 3 phosphate and", "3 phosphate and fructose", "and fructose 6 phosphate.

              the", "fructose 6 phosphate.

              the oxidative", "6 phosphate.

              the oxidative branch", "phosphate.

              the oxidative branch of", "oxidative branch of the", "branch of the pentose", "of the pentose phosphate", "phosphate pathway reactions", "pathway reactions 1", "1 3 generates", "3 generates nadph", "generates nadph and pentose", "nadph and pentose 5", "and pentose 5 phosphate.", "pentose 5 phosphate. the", "5 phosphate. the non", "phosphate. the non oxidative", "the non oxidative branch", "non oxidative branch of", "branch of the pathway", "the pathway reactions", "pathway reactions 4", "4 8 converts", "8 converts pentose", "converts pentose 5 phosphate", "pentose 5 phosphate to", "5 phosphate to other", "phosphate to other sugars.

              the", "to other sugars.

              the overall", "other sugars.

              the overall pathway", "sugars.

              the overall pathway can", "overall pathway can operate", "pathway can operate to", "can operate to generate", "operate to generate only", "to generate only nadph", "only nadph glucose", "nadph glucose 6", "glucose 6 phosphate is", "6 phosphate is converted", "phosphate is converted to", "is converted to pentose", "converted to pentose 5", "to pentose 5 phosphates", "5 phosphates which", "phosphates which are", "which are directed to", "are directed to the", "directed to the synthesis", "to the synthesis of", "the synthesis of fructose", "synthesis of fructose 6", "of fructose 6 phosphate", "fructose 6 phosphate and", "6 phosphate and glyceraldehyde", "3 phosphate which", "phosphate which in", "which in turn are", "in turn are converted", "turn are converted back", "are converted back to", "converted back to glucose", "back to glucose 6", "to glucose 6 phosphate", "glucose 6 phosphate .", "6 phosphate . the", "phosphate . the reactions", ". the reactions of", "the reactions of the", "reactions of the non", "of the non oxidative", "non oxidative branch can", "oxidative branch can operate", "branch can operate to", "operate to generate net", "to generate net amounts", "generate net amounts of", "net amounts of ribose", "amounts of ribose 5", "ribose 5 phosphate with", "5 phosphate with no", "phosphate with no production", "with no production of", "no production of nadph.", "of nadph. net", "nadph. net flux", "net flux through this", "flux through this network", "through this network of", "this network of reactions", "network of reactions appears", "of reactions appears to", "reactions appears to depend", "appears to depend on", "to depend on the", "depend on the metabolic", "on the metabolic state", "the metabolic state of", "metabolic state of the", "state of the cell", "of the cell and", "the cell and the", "cell and the nature", "and the nature of", "the nature of the", "nature of the biosynthetic", "of the biosynthetic reactions", "the biosynthetic reactions underway", "reactions underway casazza", "underway casazza and", "casazza and veech 1987", "and veech 1987 .

              g6pd", "1987 .

              g6pd the", ".

              g6pd the enzyme", "the enzyme that catalyzes", "enzyme that catalyzes the", "that catalyzes the first", "catalyzes the first reaction", "the first reaction of", "first reaction of the", "reaction of the pathway", "the pathway is", "pathway is more", "is more extensively mutated", "more extensively mutated in", "extensively mutated in human", "mutated in human populations", "in human populations than", "human populations than any", "populations than any other", "than any other enzyme", "other enzyme pehaps", "enzyme pehaps because", "pehaps because these mutant", "because these mutant alleles", "these mutant alleles confer", "mutant alleles confer malaria", "alleles confer malaria resistance", "malaria resistance luzzatto", "resistance luzzatto and", "luzzatto and afolayan 1968", "and afolayan 1968 .", "afolayan 1968 . mutations", "1968 . mutations affecting", ". mutations affecting other", "mutations affecting other parts", "affecting other parts of", "other parts of the", "parts of the pathway", "of the pathway are", "the pathway are rare", "are rare though", "rare though several", "though several have been", "several have been described", "have been described and", "been described and studies", "described and studies of", "and studies of their", "studies of their effects", "of their effects have", "their effects have contributed", "effects have contributed to", "have contributed to our", "contributed to our understanding", "to our understanding of", "our understanding of the", "understanding of the normal", "of the normal flux", "the normal flux of", "normal flux of metabolites", "flux of metabolites through", "of metabolites through this", "metabolites through this network", "of reactions wamelink", "reactions wamelink et", "wamelink et al. 2008", "et al. 2008 .", "the pentose phosphate pathway is", "pentose phosphate pathway is responsible", "phosphate pathway is responsible for", "pathway is responsible for the", "is responsible for the generation", "responsible for the generation of", "for the generation of a", "the generation of a substantial", "generation of a substantial fraction", "of a substantial fraction of", "a substantial fraction of the", "substantial fraction of the cytoplasmic", "fraction of the cytoplasmic nadph", "of the cytoplasmic nadph required", "the cytoplasmic nadph required for", "cytoplasmic nadph required for biosynthetic", "nadph required for biosynthetic reactions", "for biosynthetic reactions and", "biosynthetic reactions and for", "reactions and for the", "and for the generation of", "for the generation of ribose", "the generation of ribose 5", "generation of ribose 5 phosphate", "of ribose 5 phosphate for", "ribose 5 phosphate for nucleotide", "5 phosphate for nucleotide synthesis.", "phosphate for nucleotide synthesis. although", "for nucleotide synthesis. although the", "nucleotide synthesis. although the pentose", "synthesis. although the pentose phosphate", "although the pentose phosphate pathway", "the pentose phosphate pathway and", "pentose phosphate pathway and glycolysis", "phosphate pathway and glycolysis are", "pathway and glycolysis are distinct", "glycolysis are distinct they", "are distinct they involve", "distinct they involve three", "they involve three common intermediates", "three common intermediates glucose", "common intermediates glucose 6", "intermediates glucose 6 phosphate", "glucose 6 phosphate glyceraldehyde", "6 phosphate glyceraldehyde 3", "phosphate glyceraldehyde 3 phosphate", "fructose 6 phosphate so", "6 phosphate so the", "phosphate so the two", "so the two pathways are", "the two pathways are interconnected.", "two pathways are interconnected. the", "pathways are interconnected. the pentose", "are interconnected. the pentose phosphate", "interconnected. the pentose phosphate pathway", "the pentose phosphate pathway consists", "pentose phosphate pathway consists of", "phosphate pathway consists of eight", "pathway consists of eight reactions:1.", "consists of eight reactions:1. conversion", "of eight reactions:1. conversion glucose", "eight reactions:1. conversion glucose 6", "reactions:1. conversion glucose 6 phosphate", "conversion glucose 6 phosphate to", "glucose 6 phosphate to d", "6 phosphate to d glucono", "phosphate to d glucono 1", "to d glucono 1 5", "d glucono 1 5 lactone", "glucono 1 5 lactone 6", "1 5 lactone 6 phosphate", "lactone 6 phosphate with", "6 phosphate with the", "phosphate with the formation", "with the formation of nadph", "formation of nadph 2.", "of nadph 2. conversion", "nadph 2. conversion of", "2. conversion of d glucono", "conversion of d glucono 1", "of d glucono 1 5", "5 lactone 6 phosphate to", "lactone 6 phosphate to 6", "6 phosphate to 6 phospho", "phosphate to 6 phospho d", "to 6 phospho d gluconate", "phospho d gluconate 3.", "d gluconate 3. conversion", "gluconate 3. conversion of", "3. conversion of 6 phospho", "conversion of 6 phospho d", "of 6 phospho d gluconate", "6 phospho d gluconate to", "phospho d gluconate to ribulose", "d gluconate to ribulose 5", "gluconate to ribulose 5 phosphate", "ribulose 5 phosphate with", "5 phosphate with the", "formation of nadph 4.", "of nadph 4. conversion", "nadph 4. conversion of", "4. conversion of ribulose 5", "conversion of ribulose 5 phosphate", "of ribulose 5 phosphate to", "ribulose 5 phosphate to xylulose", "5 phosphate to xylulose 5", "phosphate to xylulose 5 phosphate", "xylulose 5 phosphate 5.", "5 phosphate 5. conversion", "phosphate 5. conversion of", "5. conversion of ribulose 5", "ribulose 5 phosphate to ribose", "5 phosphate to ribose 5", "phosphate to ribose 5 phosphate", "ribose 5 phosphate 6.", "5 phosphate 6. rearrangement", "phosphate 6. rearrangement of", "6. rearrangement of ribose 5", "rearrangement of ribose 5 phosphate", "of ribose 5 phosphate and", "ribose 5 phosphate and xylulose", "5 phosphate and xylulose 5", "phosphate and xylulose 5 phosphate", "and xylulose 5 phosphate to", "xylulose 5 phosphate to form", "5 phosphate to form sedoheptulose", "phosphate to form sedoheptulose 7", "to form sedoheptulose 7 phosphate", "form sedoheptulose 7 phosphate and", "sedoheptulose 7 phosphate and glyceraldehyde", "7 phosphate and glyceraldehyde 3", "phosphate and glyceraldehyde 3 phosphate", "glyceraldehyde 3 phosphate 7.", "3 phosphate 7. rearrangement", "phosphate 7. rearrangement of", "7. rearrangement of sedoheptulose 7", "rearrangement of sedoheptulose 7 phosphate", "of sedoheptulose 7 phosphate and", "and glyceraldehyde 3 phosphate to", "glyceraldehyde 3 phosphate to form", "3 phosphate to form erythrose", "to form erythrose 4", "form erythrose 4 phosphate", "erythrose 4 phosphate and", "4 phosphate and fructose 6", "phosphate and fructose 6 phosphate", "6 phosphate and 8.", "phosphate and 8. rearrangement", "and 8. rearrangement of xylulose", "8. rearrangement of xylulose 5", "rearrangement of xylulose 5 phosphate", "of xylulose 5 phosphate and", "xylulose 5 phosphate and erythrose", "5 phosphate and erythrose 4", "phosphate and erythrose 4 phosphate", "and erythrose 4 phosphate to", "erythrose 4 phosphate to form", "4 phosphate to form glyceraldehyde", "phosphate to form glyceraldehyde 3", "to form glyceraldehyde 3 phosphate", "form glyceraldehyde 3 phosphate and", "glyceraldehyde 3 phosphate and fructose", "3 phosphate and fructose 6", "phosphate and fructose 6 phosphate.

              the", "and fructose 6 phosphate.

              the oxidative", "fructose 6 phosphate.

              the oxidative branch", "6 phosphate.

              the oxidative branch of", "phosphate.

              the oxidative branch of the", "oxidative branch of the pentose", "branch of the pentose phosphate", "of the pentose phosphate pathway", "pentose phosphate pathway reactions", "phosphate pathway reactions 1", "pathway reactions 1 3", "reactions 1 3 generates", "1 3 generates nadph", "3 generates nadph and", "generates nadph and pentose 5", "nadph and pentose 5 phosphate.", "and pentose 5 phosphate. the", "pentose 5 phosphate. the non", "5 phosphate. the non oxidative", "phosphate. the non oxidative branch", "the non oxidative branch of", "non oxidative branch of the", "oxidative branch of the pathway", "of the pathway reactions", "the pathway reactions 4", "pathway reactions 4 8", "reactions 4 8 converts", "4 8 converts pentose", "8 converts pentose 5", "converts pentose 5 phosphate to", "pentose 5 phosphate to other", "5 phosphate to other sugars.

              the", "phosphate to other sugars.

              the overall", "to other sugars.

              the overall pathway", "other sugars.

              the overall pathway can", "sugars.

              the overall pathway can operate", "overall pathway can operate to", "pathway can operate to generate", "can operate to generate only", "operate to generate only nadph", "generate only nadph glucose", "only nadph glucose 6", "nadph glucose 6 phosphate", "glucose 6 phosphate is converted", "6 phosphate is converted to", "phosphate is converted to pentose", "is converted to pentose 5", "converted to pentose 5 phosphates", "pentose 5 phosphates which", "5 phosphates which are", "phosphates which are directed", "which are directed to the", "are directed to the synthesis", "directed to the synthesis of", "to the synthesis of fructose", "the synthesis of fructose 6", "synthesis of fructose 6 phosphate", "of fructose 6 phosphate and", "fructose 6 phosphate and glyceraldehyde", "6 phosphate and glyceraldehyde 3", "glyceraldehyde 3 phosphate which", "3 phosphate which in", "phosphate which in turn", "which in turn are converted", "in turn are converted back", "turn are converted back to", "are converted back to glucose", "converted back to glucose 6", "back to glucose 6 phosphate", "to glucose 6 phosphate .", "glucose 6 phosphate . the", "6 phosphate . the reactions", "phosphate . the reactions of", ". the reactions of the", "the reactions of the non", "reactions of the non oxidative", "of the non oxidative branch", "the non oxidative branch can", "non oxidative branch can operate", "oxidative branch can operate to", "branch can operate to generate", "can operate to generate net", "operate to generate net amounts", "to generate net amounts of", "generate net amounts of ribose", "net amounts of ribose 5", "amounts of ribose 5 phosphate", "of ribose 5 phosphate with", "ribose 5 phosphate with no", "5 phosphate with no production", "phosphate with no production of", "with no production of nadph.", "production of nadph. net", "of nadph. net flux", "nadph. net flux through", "net flux through this network", "flux through this network of", "through this network of reactions", "this network of reactions appears", "network of reactions appears to", "of reactions appears to depend", "reactions appears to depend on", "appears to depend on the", "to depend on the metabolic", "depend on the metabolic state", "on the metabolic state of", "the metabolic state of the", "metabolic state of the cell", "state of the cell and", "of the cell and the", "the cell and the nature", "cell and the nature of", "and the nature of the", "the nature of the biosynthetic", "nature of the biosynthetic reactions", "of the biosynthetic reactions underway", "biosynthetic reactions underway casazza", "reactions underway casazza and", "underway casazza and veech", "casazza and veech 1987 .

              g6pd", "veech 1987 .

              g6pd the", "1987 .

              g6pd the enzyme", ".

              g6pd the enzyme that", "the enzyme that catalyzes the", "enzyme that catalyzes the first", "that catalyzes the first reaction", "catalyzes the first reaction of", "the first reaction of the", "first reaction of the pathway", "of the pathway is", "the pathway is more", "pathway is more extensively", "is more extensively mutated in", "more extensively mutated in human", "extensively mutated in human populations", "mutated in human populations than", "in human populations than any", "human populations than any other", "populations than any other enzyme", "any other enzyme pehaps", "other enzyme pehaps because", "enzyme pehaps because these", "pehaps because these mutant alleles", "because these mutant alleles confer", "these mutant alleles confer malaria", "mutant alleles confer malaria resistance", "confer malaria resistance luzzatto", "malaria resistance luzzatto and", "resistance luzzatto and afolayan", "luzzatto and afolayan 1968 .", "and afolayan 1968 . mutations", "afolayan 1968 . mutations affecting", "1968 . mutations affecting other", ". mutations affecting other parts", "mutations affecting other parts of", "affecting other parts of the", "other parts of the pathway", "parts of the pathway are", "of the pathway are rare", "pathway are rare though", "are rare though several", "rare though several have", "though several have been described", "several have been described and", "have been described and studies", "been described and studies of", "described and studies of their", "and studies of their effects", "studies of their effects have", "of their effects have contributed", "their effects have contributed to", "effects have contributed to our", "have contributed to our understanding", "contributed to our understanding of", "to our understanding of the", "our understanding of the normal", "understanding of the normal flux", "of the normal flux of", "the normal flux of metabolites", "normal flux of metabolites through", "flux of metabolites through this", "of metabolites through this network", "metabolites through this network of", "network of reactions wamelink", "of reactions wamelink et", "reactions wamelink et al.", "wamelink et al. 2008 ." ] }, { "record_id": "GLY_000594_1_1114", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71384", "r hsa", "hsa 71384", "r hsa 71384" ] }, { "record_id": "GLY_000594_1_1114", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ethanol oxidation", "ethanol and", "and related", "related alcohols", "alcohols can", "can be", "be ingested", "ingested as", "as part", "part of", "of the", "the diet", "diet and", "and are", "are formed", "formed by", "by microorganisms", "microorganisms in", "in the", "the intestinal", "intestinal tract.", "tract. ethanol", "oxidation to", "to acetate", "acetate occurs", "occurs primarily", "primarily in", "in liver", "liver cells", "cells in", "in a", "a multistep", "multistep process", "process first", "first described", "described by", "by racker", "1949 .", ". first", "the cytosol", "ethanol is", "is oxidized", "oxidized to", "to acetaldehyde", "with the", "the formation", "formation of", "of nadh.", "nadh. second", "the mitochondrion", "acetaldehyde is", "acetate with", "nadh. finally", "acetate in", "mitochondrion can", "be condensed", "condensed with", "with coenzyme", "coenzyme a", "a to", "to form", "form acetyl", "acetyl coa.", "coa. polymorphisms", "polymorphisms in", "the enzymes", "enzymes catalyzing", "catalyzing the", "the first", "first two", "two steps", "steps are", "are associated", "associated with", "with variation", "variation in", "the efficiency", "efficiency of", "of alcohol", "alcohol catabolism", "catabolism in", "in human", "human populations", "chen et", "et al.", "al. 1999", "lange et", "al. 1976", "jornvall 1985", "1985 .", ". the", "the molecular", "molecular mechanism", "mechanism by", "by which", "which cytosolic", "cytosolic acetaldehyde", "acetaldehyde enters", "enters the", "the mitochondrial", "mitochondrial matrix", "matrix is", "is not", "not known", "lemasters 2007", "2007 .

              cytosolic", ".

              cytosolic enzymes", "enzymes capable", "capable of", "of oxidizing", "oxidizing acetaldehyde", "acetaldehyde to", "acetate have", "have also", "also been", "been identified", "identified and", "and characterized", "characterized in", "in vitro", "inoue et", "al. 1979", "so a", "a purely", "purely cytosolic", "cytosolic pathway", "pathway for", "for ethanol", "acetate and", "and conversion", "conversion to", "to acetyl", "acetyl coa", "coa can", "be annotated.", "annotated. the", "the role", "role of", "of this", "this pathway", "pathway in", "in vivo", "vivo is", "is unclear", "though limited", "limited attempts", "attempts to", "to correlate", "correlate deficiencies", "deficiencies in", "the cytosolic", "cytosolic enzyme", "enzyme with", "with alcohol", "alcohol intolerance", "intolerance have", "have yielded", "yielded suggestive", "suggestive data", "yoshida et", "al. 1989", "1989 .", ". additional", "additional peroxisomal", "peroxisomal and", "and microsomal", "microsomal pathways", "pathways for", "for the", "the oxidation", "oxidation of", "of ethanol", "ethanol to", "acetaldehyde have", "have been", "been described", "their physiological", "physiological significance", "significance is", "unclear and", "and they", "they are", "are not", "not annotated", "annotated here.", "ethanol and related", "and related alcohols", "related alcohols can", "alcohols can be", "can be ingested", "be ingested as", "ingested as part", "as part of", "part of the", "of the diet", "the diet and", "diet and are", "and are formed", "are formed by", "formed by microorganisms", "by microorganisms in", "microorganisms in the", "in the intestinal", "the intestinal tract.", "intestinal tract. ethanol", "tract. ethanol oxidation", "ethanol oxidation to", "oxidation to acetate", "to acetate occurs", "acetate occurs primarily", "occurs primarily in", "primarily in liver", "in liver cells", "liver cells in", "cells in a", "in a multistep", "a multistep process", "multistep process first", "process first described", "first described by", "described by racker", "racker 1949", "1949 . first", "first in", "in the cytosol", "cytosol ethanol", "ethanol is oxidized", "is oxidized to", "oxidized to acetaldehyde", "acetaldehyde with", "with the formation", "the formation of", "formation of nadh.", "of nadh. second", "second in", "in the mitochondrion", "mitochondrion acetaldehyde", "acetaldehyde is oxidized", "oxidized to acetate", "to acetate with", "acetate with the", "of nadh. finally", "finally acetate", "acetate in the", "the mitochondrion can", "mitochondrion can be", "can be condensed", "be condensed with", "condensed with coenzyme", "with coenzyme a", "coenzyme a to", "a to form", "to form acetyl", "form acetyl coa.", "acetyl coa. polymorphisms", "coa. polymorphisms in", "polymorphisms in the", "in the enzymes", "the enzymes catalyzing", "enzymes catalyzing the", "catalyzing the first", "the first two", "first two steps", "two steps are", "steps are associated", "are associated with", "associated with variation", "with variation in", "variation in the", "in the efficiency", "the efficiency of", "efficiency of alcohol", "of alcohol catabolism", "alcohol catabolism in", "catabolism in human", "in human populations", "populations chen", "chen et al.", "et al. 1999", "1999 lange", "lange et al.", "et al. 1976", "1976 jornvall", "jornvall 1985 .", "1985 . the", ". the molecular", "the molecular mechanism", "molecular mechanism by", "mechanism by which", "by which cytosolic", "which cytosolic acetaldehyde", "cytosolic acetaldehyde enters", "acetaldehyde enters the", "enters the mitochondrial", "the mitochondrial matrix", "mitochondrial matrix is", "matrix is not", "is not known", "known lemasters", "lemasters 2007 .

              cytosolic", "2007 .

              cytosolic enzymes", ".

              cytosolic enzymes capable", "enzymes capable of", "capable of oxidizing", "of oxidizing acetaldehyde", "oxidizing acetaldehyde to", "acetaldehyde to acetate", "to acetate have", "acetate have also", "have also been", "also been identified", "been identified and", "identified and characterized", "and characterized in", "characterized in vitro", "vitro inoue", "inoue et al.", "et al. 1979", "1979 so", "so a purely", "a purely cytosolic", "purely cytosolic pathway", "cytosolic pathway for", "pathway for ethanol", "for ethanol oxidation", "to acetate and", "acetate and conversion", "and conversion to", "conversion to acetyl", "to acetyl coa", "acetyl coa can", "coa can be", "can be annotated.", "be annotated. the", "annotated. the role", "the role of", "role of this", "of this pathway", "this pathway in", "pathway in vivo", "in vivo is", "vivo is unclear", "unclear though", "though limited attempts", "limited attempts to", "attempts to correlate", "to correlate deficiencies", "correlate deficiencies in", "deficiencies in the", "in the cytosolic", "the cytosolic enzyme", "cytosolic enzyme with", "enzyme with alcohol", "with alcohol intolerance", "alcohol intolerance have", "intolerance have yielded", "have yielded suggestive", "yielded suggestive data", "data yoshida", "yoshida et al.", "et al. 1989", "al. 1989 .", "1989 . additional", ". additional peroxisomal", "additional peroxisomal and", "peroxisomal and microsomal", "and microsomal pathways", "microsomal pathways for", "pathways for the", "for the oxidation", "the oxidation of", "oxidation of ethanol", "of ethanol to", "ethanol to acetaldehyde", "to acetaldehyde have", "acetaldehyde have been", "have been described", "described their", "their physiological significance", "physiological significance is", "significance is unclear", "is unclear and", "unclear and they", "and they are", "they are not", "are not annotated", "not annotated here.", "ethanol and related alcohols", "and related alcohols can", "related alcohols can be", "alcohols can be ingested", "can be ingested as", "be ingested as part", "ingested as part of", "as part of the", "part of the diet", "of the diet and", "the diet and are", "diet and are formed", "and are formed by", "are formed by microorganisms", "formed by microorganisms in", "by microorganisms in the", "microorganisms in the intestinal", "in the intestinal tract.", "the intestinal tract. ethanol", "intestinal tract. ethanol oxidation", "tract. ethanol oxidation to", "ethanol oxidation to acetate", "oxidation to acetate occurs", "to acetate occurs primarily", "acetate occurs primarily in", "occurs primarily in liver", "primarily in liver cells", "in liver cells in", "liver cells in a", "cells in a multistep", "in a multistep process", "a multistep process first", "multistep process first described", "process first described by", "first described by racker", "by racker 1949", "racker 1949 .", ". first in", "first in the", "the cytosol ethanol", "cytosol ethanol is", "ethanol is oxidized to", "is oxidized to acetaldehyde", "to acetaldehyde with", "acetaldehyde with the", "with the formation of", "the formation of nadh.", "formation of nadh. second", "nadh. second in", "second in the", "the mitochondrion acetaldehyde", "mitochondrion acetaldehyde is", "acetaldehyde is oxidized to", "is oxidized to acetate", "oxidized to acetate with", "to acetate with the", "acetate with the formation", "formation of nadh. finally", "nadh. finally acetate", "finally acetate in", "acetate in the mitochondrion", "in the mitochondrion can", "the mitochondrion can be", "mitochondrion can be condensed", "can be condensed with", "be condensed with coenzyme", "condensed with coenzyme a", "with coenzyme a to", "coenzyme a to form", "a to form acetyl", "to form acetyl coa.", "form acetyl coa. polymorphisms", "acetyl coa. polymorphisms in", "coa. polymorphisms in the", "polymorphisms in the enzymes", "in the enzymes catalyzing", "the enzymes catalyzing the", "enzymes catalyzing the first", "catalyzing the first two", "the first two steps", "first two steps are", "two steps are associated", "steps are associated with", "are associated with variation", "associated with variation in", "with variation in the", "variation in the efficiency", "in the efficiency of", "the efficiency of alcohol", "efficiency of alcohol catabolism", "of alcohol catabolism in", "alcohol catabolism in human", "catabolism in human populations", "human populations chen", "populations chen et", "chen et al. 1999", "al. 1999 lange", "1999 lange et", "lange et al. 1976", "al. 1976 jornvall", "1976 jornvall 1985", "jornvall 1985 . the", "1985 . the molecular", ". the molecular mechanism", "the molecular mechanism by", "molecular mechanism by which", "mechanism by which cytosolic", "by which cytosolic acetaldehyde", "which cytosolic acetaldehyde enters", "cytosolic acetaldehyde enters the", "acetaldehyde enters the mitochondrial", "enters the mitochondrial matrix", "the mitochondrial matrix is", "mitochondrial matrix is not", "matrix is not known", "not known lemasters", "known lemasters 2007", "lemasters 2007 .

              cytosolic enzymes", "2007 .

              cytosolic enzymes capable", ".

              cytosolic enzymes capable of", "enzymes capable of oxidizing", "capable of oxidizing acetaldehyde", "of oxidizing acetaldehyde to", "oxidizing acetaldehyde to acetate", "acetaldehyde to acetate have", "to acetate have also", "acetate have also been", "have also been identified", "also been identified and", "been identified and characterized", "identified and characterized in", "and characterized in vitro", "in vitro inoue", "vitro inoue et", "inoue et al. 1979", "al. 1979 so", "1979 so a", "so a purely cytosolic", "a purely cytosolic pathway", "purely cytosolic pathway for", "cytosolic pathway for ethanol", "pathway for ethanol oxidation", "for ethanol oxidation to", "oxidation to acetate and", "to acetate and conversion", "acetate and conversion to", "and conversion to acetyl", "conversion to acetyl coa", "to acetyl coa can", "acetyl coa can be", "coa can be annotated.", "can be annotated. the", "be annotated. the role", "annotated. the role of", "the role of this", "role of this pathway", "of this pathway in", "this pathway in vivo", "pathway in vivo is", "in vivo is unclear", "is unclear though", "unclear though limited", "though limited attempts to", "limited attempts to correlate", "attempts to correlate deficiencies", "to correlate deficiencies in", "correlate deficiencies in the", "deficiencies in the cytosolic", "in the cytosolic enzyme", "the cytosolic enzyme with", "cytosolic enzyme with alcohol", "enzyme with alcohol intolerance", "with alcohol intolerance have", "alcohol intolerance have yielded", "intolerance have yielded suggestive", "have yielded suggestive data", "suggestive data yoshida", "data yoshida et", "yoshida et al. 1989", "et al. 1989 .", "al. 1989 . additional", "1989 . additional peroxisomal", ". additional peroxisomal and", "additional peroxisomal and microsomal", "peroxisomal and microsomal pathways", "and microsomal pathways for", "microsomal pathways for the", "pathways for the oxidation", "for the oxidation of", "the oxidation of ethanol", "oxidation of ethanol to", "of ethanol to acetaldehyde", "ethanol to acetaldehyde have", "to acetaldehyde have been", "acetaldehyde have been described", "been described their", "described their physiological", "their physiological significance is", "physiological significance is unclear", "significance is unclear and", "is unclear and they", "unclear and they are", "and they are not", "they are not annotated", "are not annotated here.", "ethanol and related alcohols can", "and related alcohols can be", "related alcohols can be ingested", "alcohols can be ingested as", "can be ingested as part", "be ingested as part of", "ingested as part of the", "as part of the diet", "part of the diet and", "of the diet and are", "the diet and are formed", "diet and are formed by", "and are formed by microorganisms", "are formed by microorganisms in", "formed by microorganisms in the", "by microorganisms in the intestinal", "microorganisms in the intestinal tract.", "in the intestinal tract. ethanol", "the intestinal tract. ethanol oxidation", "intestinal tract. ethanol oxidation to", "tract. ethanol oxidation to acetate", "ethanol oxidation to acetate occurs", "oxidation to acetate occurs primarily", "to acetate occurs primarily in", "acetate occurs primarily in liver", "occurs primarily in liver cells", "primarily in liver cells in", "in liver cells in a", "liver cells in a multistep", "cells in a multistep process", "in a multistep process first", "a multistep process first described", "multistep process first described by", "process first described by racker", "described by racker 1949", "by racker 1949 .", "racker 1949 . first", "1949 . first in", ". first in the", "first in the cytosol", "in the cytosol ethanol", "the cytosol ethanol is", "cytosol ethanol is oxidized", "ethanol is oxidized to acetaldehyde", "oxidized to acetaldehyde with", "to acetaldehyde with the", "acetaldehyde with the formation", "with the formation of nadh.", "the formation of nadh. second", "of nadh. second in", "nadh. second in the", "second in the mitochondrion", "in the mitochondrion acetaldehyde", "the mitochondrion acetaldehyde is", "mitochondrion acetaldehyde is oxidized", "acetaldehyde is oxidized to acetate", "is oxidized to acetate with", "oxidized to acetate with the", "to acetate with the formation", "acetate with the formation of", "the formation of nadh. finally", "of nadh. finally acetate", "nadh. finally acetate in", "finally acetate in the", "acetate in the mitochondrion can", "in the mitochondrion can be", "the mitochondrion can be condensed", "mitochondrion can be condensed with", "can be condensed with coenzyme", "be condensed with coenzyme a", "condensed with coenzyme a to", "with coenzyme a to form", "coenzyme a to form acetyl", "a to form acetyl coa.", "to form acetyl coa. polymorphisms", "form acetyl coa. polymorphisms in", "acetyl coa. polymorphisms in the", "coa. polymorphisms in the enzymes", "polymorphisms in the enzymes catalyzing", "in the enzymes catalyzing the", "the enzymes catalyzing the first", "enzymes catalyzing the first two", "catalyzing the first two steps", "the first two steps are", "first two steps are associated", "two steps are associated with", "steps are associated with variation", "are associated with variation in", "associated with variation in the", "with variation in the efficiency", "variation in the efficiency of", "in the efficiency of alcohol", "the efficiency of alcohol catabolism", "efficiency of alcohol catabolism in", "of alcohol catabolism in human", "alcohol catabolism in human populations", "in human populations chen", "human populations chen et", "populations chen et al.", "et al. 1999 lange", "al. 1999 lange et", "1999 lange et al.", "et al. 1976 jornvall", "al. 1976 jornvall 1985", "1976 jornvall 1985 .", "jornvall 1985 . the molecular", "1985 . the molecular mechanism", ". the molecular mechanism by", "the molecular mechanism by which", "molecular mechanism by which cytosolic", "mechanism by which cytosolic acetaldehyde", "by which cytosolic acetaldehyde enters", "which cytosolic acetaldehyde enters the", "cytosolic acetaldehyde enters the mitochondrial", "acetaldehyde enters the mitochondrial matrix", "enters the mitochondrial matrix is", "the mitochondrial matrix is not", "mitochondrial matrix is not known", "is not known lemasters", "not known lemasters 2007", "known lemasters 2007 .

              cytosolic", "lemasters 2007 .

              cytosolic enzymes capable", "2007 .

              cytosolic enzymes capable of", ".

              cytosolic enzymes capable of oxidizing", "enzymes capable of oxidizing acetaldehyde", "capable of oxidizing acetaldehyde to", "of oxidizing acetaldehyde to acetate", "oxidizing acetaldehyde to acetate have", "acetaldehyde to acetate have also", "to acetate have also been", "acetate have also been identified", "have also been identified and", "also been identified and characterized", "been identified and characterized in", "identified and characterized in vitro", "characterized in vitro inoue", "in vitro inoue et", "vitro inoue et al.", "et al. 1979 so", "al. 1979 so a", "1979 so a purely", "so a purely cytosolic pathway", "a purely cytosolic pathway for", "purely cytosolic pathway for ethanol", "cytosolic pathway for ethanol oxidation", "pathway for ethanol oxidation to", "for ethanol oxidation to acetate", "ethanol oxidation to acetate and", "oxidation to acetate and conversion", "to acetate and conversion to", "acetate and conversion to acetyl", "and conversion to acetyl coa", "conversion to acetyl coa can", "to acetyl coa can be", "acetyl coa can be annotated.", "coa can be annotated. the", "can be annotated. the role", "be annotated. the role of", "annotated. the role of this", "the role of this pathway", "role of this pathway in", "of this pathway in vivo", "this pathway in vivo is", "pathway in vivo is unclear", "vivo is unclear though", "is unclear though limited", "unclear though limited attempts", "though limited attempts to correlate", "limited attempts to correlate deficiencies", "attempts to correlate deficiencies in", "to correlate deficiencies in the", "correlate deficiencies in the cytosolic", "deficiencies in the cytosolic enzyme", "in the cytosolic enzyme with", "the cytosolic enzyme with alcohol", "cytosolic enzyme with alcohol intolerance", "enzyme with alcohol intolerance have", "with alcohol intolerance have yielded", "alcohol intolerance have yielded suggestive", "intolerance have yielded suggestive data", "yielded suggestive data yoshida", "suggestive data yoshida et", "data yoshida et al.", "yoshida et al. 1989 .", "et al. 1989 . additional", "al. 1989 . additional peroxisomal", "1989 . additional peroxisomal and", ". additional peroxisomal and microsomal", "additional peroxisomal and microsomal pathways", "peroxisomal and microsomal pathways for", "and microsomal pathways for the", "microsomal pathways for the oxidation", "pathways for the oxidation of", "for the oxidation of ethanol", "the oxidation of ethanol to", "oxidation of ethanol to acetaldehyde", "of ethanol to acetaldehyde have", "ethanol to acetaldehyde have been", "to acetaldehyde have been described", "have been described their", "been described their physiological", "described their physiological significance", "their physiological significance is unclear", "physiological significance is unclear and", "significance is unclear and they", "is unclear and they are", "unclear and they are not", "and they are not annotated", "they are not annotated here." ] }, { "record_id": "GLY_000594_1_1115", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72165", "r hsa", "hsa 72165", "r hsa 72165" ] }, { "record_id": "GLY_000594_1_1115", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna splicing", "minor pathway", "splicing minor", "mrna splicing minor", "splicing minor pathway", "the splicing", "splicing of", "of a", "a subset", "subset of", "of pre", "pre mrna", "mrna introns", "introns occurs", "occurs by", "by a", "a second", "second pathway", "designated the", "the at", "at ac", "ac or", "or u12", "u12 dependent", "dependent splicing", "splicing pathway.", "ac introns", "introns have", "have highly", "highly conserved", "non canonical", "canonical splice", "splice sites", "sites that", "that are", "are removed", "removed by", "by the", "ac spliceosome", "which contains", "contains distinct", "distinct snrnas", "are structurally", 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spliceosome. u5 snrna", "spliceosome. u5 snrna as", "u5 snrna as well", "snrna as well as", "as well as many", "well as many of", "as many of the", "many of the protein", "of the protein factors", "the protein factors appear", "protein factors appear to", "factors appear to be", "appear to be conserved", "to be conserved between", "be conserved between the", "conserved between the two", "between the two spliceosomes.", "the splicing of a subset", "splicing of a subset of", "of a subset of pre", "a subset of pre mrna", "subset of pre mrna introns", "of pre mrna introns occurs", "pre mrna introns occurs by", "mrna introns occurs by a", "introns occurs by a second", "occurs by a second pathway", "a second pathway designated", "second pathway designated the", "pathway designated the at", "designated the at ac or", "the at ac or u12", "at ac or u12 dependent", "ac or u12 dependent splicing", "or u12 dependent splicing pathway.", "dependent splicing pathway. at", "splicing pathway. at ac", 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nine", "an average of nine introns", "average of nine introns per", "of nine introns per gene", "introns per gene which", "per gene which cannot", "gene which cannot serve", "which cannot serve as splicing", "cannot serve as splicing substrates", "serve as splicing substrates until", "as splicing substrates until both", "splicing substrates until both 5'", "substrates until both 5' and", "until both 5' and 3'", "both 5' and 3' ends", "5' and 3' ends of", "and 3' ends of each", "3' ends of each intron", "ends of each intron are", "of each intron are synthesized.", "each intron are synthesized. thus", "intron are synthesized. thus the", "are synthesized. thus the time", "synthesized. thus the time that", "thus the time that it", "the time that it takes", "time that it takes for", "that it takes for pol", "it takes for pol ii", "takes for pol ii to", "for pol ii to synthesize", "pol ii to synthesize each", "ii to synthesize each intron", "to synthesize each intron defines", "synthesize 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could occur", "which splicing could occur co", "splicing could occur co transcriptionally.", "could occur co transcriptionally. thus", "co transcriptionally. thus the", "transcriptionally. thus the kinetics", "thus the kinetics of", "the kinetics of transcription can", "kinetics of transcription can affect", "of transcription can affect the", "transcription can affect the kinetics", "can affect the kinetics of", "affect the kinetics of splicing.any", "the kinetics of splicing.any covalent", "kinetics of splicing.any covalent change", "of splicing.any covalent change in", "splicing.any covalent change in a", "covalent change in a primary", "in a primary nascent", "primary nascent mrna", "nascent mrna transcript is", "mrna transcript is mrna processing.", "is mrna processing. for", "mrna processing. for successful", "processing. for successful gene", "successful gene expression the", "gene expression the primary", "expression the primary mrna", "the primary mrna transcript needs", 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ribonucleotides", "as a few ribonucleotides have", "a few ribonucleotides have been", "few ribonucleotides have been synthesized", "ribonucleotides have been synthesized during", "have been synthesized during transcription", "been synthesized during transcription by", "synthesized during transcription by rna", "during transcription by rna polymerase", "transcription by rna polymerase ii", "rna polymerase ii through", "polymerase ii through the", "ii through the export", "through the export of the", "the export of the mature", "export of the mature mrna", "of the mature mrna to", "the mature mrna to the", "mature mrna to the cytoplasm", "to the cytoplasm and", "the cytoplasm and culminate", "cytoplasm and culminate with", "and culminate with mrna turnover", "culminate with mrna turnover in", "with mrna turnover in the", "mrna turnover in the cytoplasm." ] }, { "record_id": "GLY_000594_1_1117", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "73621", "r hsa", "hsa 73621", "r hsa 73621" ] }, { "record_id": "GLY_000594_1_1117", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pyrimidine catabolism", "in parallel", "parallel sequences", "sequences of", "of three", "three reactions", "reactions each", "thymine is", "is converted", "converted to", "to beta", "beta aminoisobutyrate", "aminoisobutyrate and", "and uracil", "uracil is", "beta alanine.", "alanine. both", "both of", "of these", "these molecules", "molecules are", "are excreted", "excreted in", "in human", "human urine", "urine and", "and appear", "appear to", "to be", "be normal", "normal end", "end products", "products of", "of pyrimidine", "griffith 1986", "webster et", "et al.", "al. 2001", "2001 .", ". mitochondrial", "mitochondrial agxt2", "can also", "also catalyze", "catalyze the", "the transamination", "transamination of", "of both", "both molecules", "molecules with", "with pyruvate", "yielding 2", "2 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domain binds", "ptb domain binds to", "domain binds to the", "binds to the insulin", "to the insulin receptor", "the insulin receptor at", "insulin receptor at the", "receptor at the juxtamembrane", "at the juxtamembrane region", "the juxtamembrane region at", "juxtamembrane region at tyrosine", "region at tyrosine 972.", "at tyrosine 972. the", "tyrosine 972. the interaction", "972. the interaction is", "the interaction is further", "interaction is further stabilized", "is further stabilized by", "further stabilized by the", "stabilized by the ph", "by the ph domain", "the ph domain of", "ph domain of irs1", "domain of irs1 which", "of irs1 which interacts", "irs1 which interacts with", "which interacts with the", "interacts with the phospholipids", "with the phospholipids of", "the phospholipids of the", "phospholipids of the plasma", "of the plasma membrane.", "the plasma membrane. this", "plasma membrane. this allows", "membrane. this allows the", "this allows the receptor", 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"GLY_000594_1_1124", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "74752", "r hsa", "hsa 74752", "r hsa 74752" ] }, { "record_id": "GLY_000594_1_1124", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by insulin", "insulin receptor", "signaling by insulin", "by insulin receptor", "signaling by insulin receptor", "insulin binding", "binding to", "to its", "its receptor", "receptor results", "results in", "in receptor", "receptor autophosphorylation", "autophosphorylation on", "on tyrosine", "tyrosine residues", "residues and", "and the", "the tyrosine", "tyrosine phosphorylation", "phosphorylation of", "of insulin", "receptor substrates", "e.g. irs", "irs and", "and shc", "by the", "the insulin", "receptor tyrosine", "tyrosine kinase.", "this allows", "allows association", "association of", "of irss", "irss with", "with downstream", "downstream effectors", "effectors such", 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              signal transduction by the", "transduction by the insulin", "the insulin receptor is", "insulin receptor is not", "receptor is not limited", "is not limited to", "not limited to its", "limited to its activation", "to its activation at", "its activation at the", "activation at the cell", "at the cell surface.", "cell surface. the", "surface. the activated", "the activated ligand receptor", "activated ligand receptor complex", "ligand receptor complex initially", "receptor complex initially at", "complex initially at the", "initially at the cell", "at the cell surface", "cell surface is", "surface is internalised", "is internalised into endosomes", "internalised into endosomes itself", "into endosomes itself a", "endosomes itself a process", "itself a process which", "a process which is", "process which is dependent", "which is dependent on", "is dependent on tyrosine", "dependent on tyrosine autophosphorylation.", "tyrosine autophosphorylation. endocytosis", "autophosphorylation. endocytosis of", "endocytosis of activated receptors", "of activated receptors has", "activated receptors has the", "receptors has the dual", "has the dual effect", "the dual effect of", "dual effect of concentrating", "effect of concentrating receptors", "of concentrating receptors within", "concentrating receptors within endosomes", "receptors within endosomes and", "within endosomes and allows", "endosomes and allows the", "and allows the insulin", "allows the insulin receptor", "insulin receptor tyrosine kinase", "receptor tyrosine kinase to", "tyrosine kinase to phosphorylate", "kinase to phosphorylate substrates", "to phosphorylate substrates that", "phosphorylate substrates that are", "substrates that are spatially", "that are spatially distinct", "are spatially distinct from", "spatially distinct from those", "distinct from those accessible", "from those accessible at", "those accessible at the", "accessible at the plasma", "at the plasma membrane.", "plasma membrane. acidification", "membrane. acidification of", "acidification of the endosomal", "of the endosomal lumen", "endosomal lumen due", "lumen due to", "due to the presence", "to the presence of", "the presence of proton", "presence of proton pumps", "proton pumps results", "pumps results in", "results in dissociation of", "in dissociation of insulin", "dissociation of insulin from", "of insulin from its", "insulin from its receptor.", "receptor. the", "the endosome constitutes the", "endosome constitutes the major", "constitutes the major site", "the major site of", "major site of insulin", "site of insulin degradation", "of insulin degradation .", ". this", "this loss of the", "loss of the ligand", "of the ligand receptor", "the ligand receptor complex", "ligand receptor complex attenuates", "receptor complex attenuates any", "complex attenuates any further", "attenuates any further insulin", "any further insulin driven", "further insulin driven receptor", "insulin driven receptor re", "driven receptor re phosphorylation", "receptor re phosphorylation events", "re phosphorylation events and", "phosphorylation events and leads", "events and leads to", "and leads to receptor", "leads to receptor dephosphorylation", "to receptor dephosphorylation by", "receptor dephosphorylation by extra", "dephosphorylation by extra lumenal", "by extra lumenal endosomally", "extra lumenal endosomally associated", "lumenal endosomally associated protein", "endosomally associated protein tyrosine", "associated protein tyrosine phosphatases", "tyrosine phosphatases ptps", "phosphatases ptps .", "ptps . the identity", ". the identity of", "the identity of these", "identity of these ptps", "of these ptps is", "these ptps is not", "ptps is not clearly", "is not clearly established", "not clearly established yet.", "insulin binding to its receptor", "binding to its receptor results", "to its receptor results in", "its receptor results in receptor", "receptor results in receptor autophosphorylation", "results in receptor autophosphorylation on", "in receptor autophosphorylation on tyrosine", "receptor autophosphorylation on tyrosine residues", "autophosphorylation on tyrosine residues and", "on tyrosine residues and the", "tyrosine residues and the tyrosine", "residues and the tyrosine phosphorylation", "and the tyrosine phosphorylation of", "the tyrosine phosphorylation of insulin", "tyrosine phosphorylation of insulin receptor", "phosphorylation of insulin receptor substrates", "insulin receptor substrates e.g.", "receptor substrates e.g. irs", "substrates e.g. irs and", "irs and shc by", "and shc by the", "shc by the insulin", "by the insulin receptor tyrosine", "the insulin receptor tyrosine kinase.", "receptor tyrosine kinase. this", "tyrosine kinase. this allows", "kinase. this allows association", "this allows association of irss", "allows association of irss with", "association of irss with downstream", "of irss with downstream effectors", "irss with downstream effectors such", "with downstream effectors such as", "downstream effectors such as pi", "effectors such as pi 3k", "such as pi 3k via", "as pi 3k via its", "pi 3k via its src", "3k via its src homology", "via its src homology 2", "src homology 2 sh2", "2 sh2 domains", "sh2 domains leading to", "domains leading to end point", "leading to end point events", "to end point events such", "end point events such as", "point events such as glut4", "such as glut4 slc2a4", "glut4 slc2a4 translocation.", "slc2a4 translocation. shc", "translocation. shc when tyrosine", "shc when tyrosine phosphorylated associates", "when tyrosine phosphorylated associates with", "tyrosine phosphorylated associates with grb2", "phosphorylated associates with grb2 and", "associates with grb2 and can", "with grb2 and can thus", "grb2 and can thus activate", "and can thus activate the", "can thus activate the ras/mapk", "thus activate the ras/mapk pathway", "activate the ras/mapk pathway independent", "the ras/mapk pathway independent of", "ras/mapk pathway independent of the", "pathway independent of the irss.

              signal", "independent of the irss.

              signal transduction", "of the irss.

              signal transduction by", "the irss.

              signal transduction by the", "irss.

              signal transduction by the insulin", "transduction by the insulin receptor", "by the insulin receptor is", "the insulin receptor is not", "insulin receptor is not limited", "receptor is not limited to", "is not limited to its", "not limited to its activation", "limited to its activation at", "to its activation at the", "its activation at the cell", "activation at the cell surface.", "the cell surface. the", "cell surface. the activated", "surface. the activated ligand", "the activated ligand receptor complex", "activated ligand receptor complex initially", "ligand receptor complex initially at", "receptor complex initially at the", "complex initially at the cell", "initially at the cell surface", "the cell surface is", "cell surface is internalised", "surface is internalised into", "is internalised into endosomes itself", "internalised into endosomes itself a", "into endosomes itself a process", "endosomes itself a process which", "itself a process which is", "a process which is dependent", "process which is dependent on", "which is dependent on tyrosine", "is dependent on tyrosine autophosphorylation.", "on tyrosine autophosphorylation. endocytosis", "tyrosine autophosphorylation. endocytosis of", "autophosphorylation. endocytosis of activated", "endocytosis of activated receptors has", "of activated receptors has the", "activated receptors has the dual", "receptors has the dual effect", "has the dual effect of", "the dual effect of concentrating", "dual effect of concentrating receptors", "effect of concentrating receptors within", "of concentrating receptors within endosomes", "concentrating receptors within endosomes and", "receptors within endosomes and allows", "within endosomes and allows the", "endosomes and allows the insulin", "and allows the insulin receptor", "allows the insulin receptor tyrosine", "the insulin receptor tyrosine kinase", "insulin receptor tyrosine kinase to", "receptor tyrosine kinase to phosphorylate", "tyrosine kinase to phosphorylate substrates", "kinase to phosphorylate substrates that", "to phosphorylate substrates that are", "phosphorylate substrates that are spatially", "substrates that are spatially distinct", "that are spatially distinct from", "are spatially distinct from those", "spatially distinct from those accessible", "distinct from those accessible at", "from those accessible at the", "those accessible at the plasma", "accessible at the plasma membrane.", "the plasma membrane. acidification", "plasma membrane. acidification of", "membrane. acidification of the", "acidification of the endosomal lumen", "the endosomal lumen due", "endosomal lumen due to", "lumen due to the", "due to the presence of", "to the presence of proton", "the presence of proton pumps", "of proton pumps results", "proton pumps results in", "pumps results in dissociation", "results in dissociation of insulin", "in dissociation of insulin from", "dissociation of insulin from its", "of insulin from its receptor.", "its receptor. the", "receptor. the endosome", "the endosome constitutes the major", "endosome constitutes the major site", "constitutes the major site of", "the major site of insulin", "major site of insulin degradation", "site of insulin degradation .", "degradation . this", ". this loss", "this loss of the ligand", "loss of the ligand receptor", "of the ligand receptor complex", "the ligand receptor complex attenuates", "ligand receptor complex attenuates any", "receptor complex attenuates any further", "complex attenuates any further insulin", "attenuates any further insulin driven", "any further insulin driven receptor", "further insulin driven receptor re", "insulin driven receptor re phosphorylation", "driven receptor re phosphorylation events", "receptor re phosphorylation events and", "re phosphorylation events and leads", "phosphorylation events and leads to", "events and leads to receptor", "and leads to receptor dephosphorylation", "leads to receptor dephosphorylation by", "to receptor dephosphorylation by extra", "receptor dephosphorylation by extra lumenal", "dephosphorylation by extra lumenal endosomally", "by extra lumenal endosomally associated", "extra lumenal endosomally associated protein", "lumenal endosomally associated protein tyrosine", "endosomally associated protein tyrosine phosphatases", "protein tyrosine phosphatases ptps", "tyrosine phosphatases ptps .", "phosphatases ptps . the", "ptps . the identity of", ". the identity of these", "the identity of these ptps", "identity of these ptps is", "of these ptps is not", "these ptps is not clearly", "ptps is not clearly established", "is not clearly established yet." ] }, { "record_id": "GLY_000594_1_1125", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75109", "r hsa", "hsa 75109", "r hsa 75109" ] }, { "record_id": "GLY_000594_1_1125", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "triglyceride biosynthesis", "the overall", "overall process", "process of", "of triglyceride", "biosynthesis consists", "consists of", "of four", "four biochemical", "biochemical pathways:", "pathways: fatty", "fatty acyl", "acyl coa", "coa biosynthesis", "conversion of", "of fatty", "coa to", "to phosphatidic", "phosphatidic acid", "of phosphatidic", "acid to", "to diacylglycerol", "and conversion", "of diacylglycerol", "diacylglycerol to", "to triacylglycerol.", "the overall process", "overall process of", "process of triglyceride", "triglyceride triacylglycerol", "triacylglycerol biosynthesis", "biosynthesis consists of", "consists of four", "of four biochemical", "four biochemical pathways:", "biochemical pathways: fatty", "pathways: fatty acyl", "fatty acyl coa", "acyl coa biosynthesis", "biosynthesis conversion", "conversion of fatty", "of fatty acyl", "acyl coa to", "coa to phosphatidic", "to phosphatidic acid", "acid conversion", "conversion of phosphatidic", "of phosphatidic acid", "phosphatidic acid to", "acid to diacylglycerol", "diacylglycerol and", "and conversion of", "conversion of diacylglycerol", "of diacylglycerol to", "diacylglycerol to triacylglycerol.", "the overall process of", "overall process of triglyceride", "of triglyceride triacylglycerol", "triacylglycerol biosynthesis consists", "biosynthesis consists of four", "consists of four biochemical", "of four biochemical pathways:", "four biochemical pathways: fatty", "biochemical pathways: fatty acyl", "pathways: fatty acyl coa", "fatty acyl coa biosynthesis", "coa biosynthesis conversion", "biosynthesis conversion of", "conversion of fatty acyl", "of fatty acyl coa", "fatty acyl coa to", "acyl coa to phosphatidic", "coa to phosphatidic acid", "phosphatidic acid conversion", "acid conversion of", "conversion of phosphatidic acid", "of phosphatidic acid to", "phosphatidic acid to diacylglycerol", "to diacylglycerol and", "diacylglycerol and conversion", "and conversion of diacylglycerol", "conversion of diacylglycerol to", "of diacylglycerol to triacylglycerol.", "the overall process of triglyceride", "process of triglyceride triacylglycerol", "triglyceride triacylglycerol biosynthesis", "triacylglycerol biosynthesis consists of", "biosynthesis consists of four biochemical", "consists of four biochemical pathways:", "of four biochemical pathways: fatty", "four biochemical pathways: fatty acyl", "biochemical pathways: fatty acyl coa", "pathways: fatty acyl coa biosynthesis", "acyl coa biosynthesis conversion", "coa biosynthesis conversion of", "biosynthesis conversion of fatty", "conversion of fatty acyl coa", "of fatty acyl coa to", "fatty acyl coa to phosphatidic", "acyl coa to phosphatidic acid", "to phosphatidic acid conversion", "phosphatidic acid conversion of", "acid conversion of phosphatidic", "conversion of phosphatidic acid to", "of phosphatidic acid to diacylglycerol", "acid to diacylglycerol and", "to diacylglycerol and conversion", "diacylglycerol and conversion of", "and conversion of diacylglycerol to", "conversion of diacylglycerol to triacylglycerol." ] }, { "record_id": "GLY_000594_1_1126", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75205", "r hsa", "hsa 75205", "r hsa 75205" ] }, { "record_id": "GLY_000594_1_1126", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dissolution of", "of fibrin", "fibrin clot", "dissolution of fibrin", "of fibrin clot", "dissolution of fibrin clot", "the crosslinked", "crosslinked fibrin", "fibrin multimers", "multimers in", "in a", "a clot", "clot are", "are broken", "broken down", "down to", "to soluble", "soluble polypeptides", "polypeptides by", "by plasmin", "a serine", "serine protease.", "protease. plasmin", "plasmin can", "can be", "be generated", "generated from", "from its", "its inactive", "inactive precursor", "precursor plasminogen", "plasminogen and", "and recruited", "recruited to", "to the", "the site", "site of", "of a", "a fibrin", "clot in", "in two", "two ways", "by interaction", "interaction with", "with tissue", "tissue plasminogen", "plasminogen activator", "activator at", "at the", "the surface", "surface of", "and by", "with urokinase", "urokinase plasminogen", "at a", "a cell", "cell surface.", "surface. the", "the first", "first mechanism", "mechanism appears", "appears to", "to be", "be the", "the major", "major one", "one responsible", "responsible for", "for the", "the dissolution", "of clots", "clots within", "within blood", "blood vessels.", "vessels. the", "the second", "although capable", "capable of", "of mediating", "mediating clot", "clot dissolution", "may normally", "normally play", "play a", "a major", "major role", "role in", "in tissue", "tissue remodeling", "cell migration", "and inflammation", "chapman 1997", "lijnen 2001", "2001 .
              clot", ".
              clot dissolution", "dissolution is", "is regulated", "regulated in", "two ways.", "ways. first", "efficient plasmin", "plasmin activation", "activation and", "and fibrinolysis", "fibrinolysis occur", "occur only", "only in", "in complexes", "complexes formed", "formed at", "the clot", "clot surface", "surface or", "or on", "on a", "cell membrane", "proteins free", "free in", "in the", "the blood", "blood are", "are inefficient", "inefficient catalysts", "catalysts and", "and are", "are rapidly", "rapidly inactivated.", "inactivated. second", "both plasminogen", "plasminogen activators", "activators and", "and plasmin", "plasmin itself", "itself are", "are inactivated", "inactivated by", "by specific", "specific serpins", "proteins that", "that bind", "bind to", "to serine", "serine proteases", "proteases to", "to form", "form stable", "enzymatically inactive", "inactive complexes", "kohler and", "and grant", "grant 2000", "2000 .
              these", ".
              these events", "events are", "are outlined", "outlined in", "the drawing:", "drawing: black", "black arrows", "arrows connect", "connect the", "the substrates", "and products", "of individual", "individual reactions", "and blue", "blue lines", "lines connect", "connect output", "output activated", "activated enzymes", "enzymes to", "the other", "other reactions", "reactions that", "that they", "they catalyze.", "the crosslinked fibrin", "crosslinked fibrin multimers", "fibrin multimers in", "multimers in a", "in a clot", "a clot are", "clot are broken", "are broken down", "broken down to", "down to soluble", "to soluble polypeptides", "soluble polypeptides by", "polypeptides by plasmin", "plasmin a", "a serine protease.", "serine protease. plasmin", "protease. plasmin can", "plasmin can be", "can be generated", "be generated from", "generated from its", "from its inactive", "its inactive precursor", "inactive precursor plasminogen", "precursor plasminogen and", "plasminogen and recruited", "and recruited to", "recruited to the", "to the site", "the site of", "site of a", "of a fibrin", "a fibrin clot", "fibrin clot in", "clot in two", "in two ways", "ways by", "by interaction with", "interaction with tissue", "with tissue plasminogen", "tissue plasminogen activator", "plasminogen activator at", "activator at the", "at the surface", "the surface of", "surface of a", "clot and", "and by interaction", "interaction with urokinase", "with urokinase plasminogen", "urokinase plasminogen activator", "activator at a", "at a cell", "a cell surface.", "cell surface. the", "surface. the first", "the first mechanism", "first mechanism appears", "mechanism appears to", "appears to be", "to be the", "be the major", "the major one", "major one responsible", "one responsible for", "responsible for the", "for the dissolution", "the dissolution of", "dissolution of clots", "of clots within", "clots within blood", "within blood vessels.", "blood vessels. the", "vessels. the second", "second although", "although capable of", "capable of mediating", "of mediating clot", "mediating clot dissolution", "dissolution may", "may normally play", "normally play a", "play a major", "a major role", "major role in", "role in tissue", "in tissue remodeling", "remodeling cell", "migration and", "inflammation chapman", "1997 lijnen", "lijnen 2001 .
              clot", "2001 .
              clot dissolution", ".
              clot dissolution is", "dissolution is regulated", "is regulated in", "regulated in two", "in two ways.", "two ways. first", "first efficient", "efficient plasmin activation", "plasmin activation and", "activation and fibrinolysis", "and fibrinolysis occur", "fibrinolysis occur only", "occur only in", "only in complexes", "in complexes formed", "complexes formed at", "formed at the", "at the clot", "the clot surface", "clot surface or", "surface or on", "or on a", "on a cell", "a cell membrane", "proteins free in", "free in the", "in the blood", "the blood are", "blood are inefficient", "are inefficient catalysts", "inefficient catalysts and", "catalysts and are", "and are rapidly", "are rapidly inactivated.", "rapidly inactivated. second", "second both", "both plasminogen activators", "plasminogen activators and", "activators and plasmin", "and plasmin itself", "plasmin itself are", "itself are inactivated", "are inactivated by", "inactivated by specific", "by specific serpins", "serpins proteins", "proteins that bind", "that bind to", "bind to serine", "to serine proteases", "serine proteases to", "proteases to form", "to form stable", "stable enzymatically", "enzymatically inactive complexes", "complexes kohler", "kohler and grant", "and grant 2000", "grant 2000 .
              these", "2000 .
              these events", ".
              these events are", "events are outlined", "are outlined in", "outlined in the", "in the drawing:", "the drawing: black", "drawing: black arrows", "black arrows connect", "arrows connect the", "connect the substrates", "substrates inputs", "inputs and", "products outputs", "outputs of", "of individual reactions", "reactions and", "and blue lines", "blue lines connect", "lines connect output", "connect output activated", "output activated enzymes", "activated enzymes to", "enzymes to the", "to the other", "the other reactions", "other reactions that", "reactions that they", "that they catalyze.", "the crosslinked fibrin multimers", "crosslinked fibrin multimers in", "fibrin multimers in a", "multimers in a clot", "in a clot are", "a clot are broken", "clot are broken down", "are broken down to", "broken down to soluble", "down to soluble polypeptides", "to soluble polypeptides by", "soluble polypeptides by plasmin", "by plasmin a", "plasmin a serine", "a serine protease. plasmin", "serine protease. plasmin can", "protease. plasmin can be", "plasmin can be generated", "can be generated from", "be generated from its", "generated from its inactive", "from its inactive precursor", "its inactive precursor plasminogen", "inactive precursor plasminogen and", "precursor plasminogen and recruited", "plasminogen and recruited to", "and recruited to the", "recruited to the site", "to the site of", "the site of a", "site of a fibrin", "of a fibrin clot", "a fibrin clot in", "fibrin clot in two", "clot in two ways", "two ways by", "ways by interaction", "by interaction with tissue", "interaction with tissue plasminogen", "with tissue plasminogen activator", "tissue plasminogen activator at", "plasminogen activator at the", "activator at the surface", "at the surface of", "the surface of a", "surface of a fibrin", "fibrin clot and", "clot and by", "and by interaction with", "by interaction with urokinase", "interaction with urokinase plasminogen", "with urokinase plasminogen activator", "urokinase plasminogen activator at", "plasminogen activator at a", "activator at a cell", "at a cell surface.", "a cell surface. the", "cell surface. the first", "surface. the first mechanism", "the first mechanism appears", "first mechanism appears to", "mechanism appears to be", "appears to be the", "to be the major", "be the major one", "the major one responsible", "major one responsible for", "one responsible for the", "responsible for the dissolution", "for the dissolution of", "the dissolution of clots", "dissolution of clots within", "of clots within blood", "clots within blood vessels.", "within blood vessels. the", "blood vessels. the second", "the second although", "second although capable", "although capable of mediating", "capable of mediating clot", "of mediating clot dissolution", "clot dissolution may", "dissolution may normally", "may normally play a", "normally play a major", "play a major role", "a major role in", "major role in tissue", "role in tissue remodeling", "tissue remodeling cell", "remodeling cell migration", "cell migration and", "migration and inflammation", "and inflammation chapman", "inflammation chapman 1997", "chapman 1997 lijnen", "1997 lijnen 2001", "lijnen 2001 .
              clot dissolution", "2001 .
              clot dissolution is", ".
              clot dissolution is regulated", "dissolution is regulated in", "is regulated in two", "regulated in two ways.", "in two ways. first", "ways. first efficient", "first efficient plasmin", "efficient plasmin activation and", "plasmin activation and fibrinolysis", "activation and fibrinolysis occur", "and fibrinolysis occur only", "fibrinolysis occur only in", "occur only in complexes", "only in complexes formed", "in complexes formed at", "complexes formed at the", "formed at the clot", "at the clot surface", "the clot surface or", "clot surface or on", "surface or on a", "or on a cell", "on a cell membrane", "membrane proteins", "proteins free in the", "free in the blood", "in the blood are", "the blood are inefficient", "blood are inefficient catalysts", "are inefficient catalysts and", "inefficient catalysts and are", "catalysts and are rapidly", "and are rapidly inactivated.", "are rapidly inactivated. second", "inactivated. second both", "second both plasminogen", "both plasminogen activators and", "plasminogen activators and plasmin", "activators and plasmin itself", "and plasmin itself are", "plasmin itself are inactivated", "itself are inactivated by", "are inactivated by specific", "inactivated by specific serpins", "specific serpins proteins", "serpins proteins that", "proteins that bind to", "that bind to serine", "bind to serine proteases", "to serine proteases to", "serine proteases to form", "proteases to form stable", "form stable enzymatically", "stable enzymatically inactive", "inactive complexes kohler", "complexes kohler and", "kohler and grant 2000", "and grant 2000 .
              these", "grant 2000 .
              these events", "2000 .
              these events are", ".
              these events are outlined", "events are outlined in", "are outlined in the", "outlined in the drawing:", "in the drawing: black", "the drawing: black arrows", "drawing: black arrows connect", "black arrows connect the", "arrows connect the substrates", "the substrates inputs", "inputs and products", "and products outputs", "outputs of individual", "individual reactions and", "reactions and blue", "and blue lines connect", "blue lines connect output", "lines connect output activated", "connect output activated enzymes", "output activated enzymes to", "activated enzymes to the", "enzymes to the other", "to the other reactions", "the other reactions that", "other reactions that they", "reactions that they catalyze.", "the crosslinked fibrin multimers in", "crosslinked fibrin multimers in a", "fibrin multimers in a clot", "multimers in a clot are", "in a clot are broken", "a clot are broken down", "clot are broken down to", "are broken down to soluble", "broken down to soluble polypeptides", "down to soluble polypeptides by", "to soluble polypeptides by plasmin", "polypeptides by plasmin a", "by plasmin a serine", "plasmin a serine protease.", "a serine protease. plasmin can", "serine protease. plasmin can be", "protease. plasmin can be generated", "plasmin can be generated from", "can be generated from its", "be generated from its inactive", "generated from its inactive precursor", "from its inactive precursor plasminogen", "its inactive precursor plasminogen and", "inactive precursor plasminogen and recruited", "precursor plasminogen and recruited to", "plasminogen and recruited to the", "and recruited to the site", "recruited to the site of", "to the site of a", "the site of a fibrin", "site of a fibrin clot", "of a fibrin clot in", "a fibrin clot in two", "fibrin clot in two ways", "in two ways by", "two ways by interaction", "ways by interaction with", "by interaction with tissue plasminogen", "interaction with tissue plasminogen activator", "with tissue plasminogen activator at", "tissue plasminogen activator at the", "plasminogen activator at the surface", "activator at the surface of", "at the surface of a", "the surface of a fibrin", "surface of a fibrin clot", "a fibrin clot and", "fibrin clot and by", "clot and by interaction", "and by interaction with urokinase", "by interaction with urokinase plasminogen", "interaction with urokinase plasminogen activator", "with urokinase plasminogen activator at", "urokinase plasminogen activator at a", "plasminogen activator at a cell", "activator at a cell surface.", "at a cell surface. the", "a cell surface. the first", "cell surface. the first mechanism", "surface. the first mechanism appears", "the first mechanism appears to", "first mechanism appears to be", "mechanism appears to be the", "appears to be the major", "to be the major one", "be the major one responsible", "the major one responsible for", "major one responsible for the", "one responsible for the dissolution", "responsible for the dissolution of", "for the dissolution of clots", "the dissolution of clots within", "dissolution of clots within blood", "of clots within blood vessels.", "clots within blood vessels. the", "within blood vessels. the second", "vessels. the second although", "the second although capable", "second although capable of", "although capable of mediating clot", "capable of mediating clot dissolution", "mediating clot dissolution may", "clot dissolution may normally", "dissolution may normally play", "may normally play a major", "normally play a major role", "play a major role in", "a major role in tissue", "major role in tissue remodeling", "in tissue remodeling cell", "tissue remodeling cell migration", "cell migration and inflammation", "and inflammation chapman 1997", "chapman 1997 lijnen 2001", "1997 lijnen 2001 .
              clot", "lijnen 2001 .
              clot dissolution is", "2001 .
              clot dissolution is regulated", ".
              clot dissolution is regulated in", "dissolution is regulated in two", "is regulated in two ways.", "regulated in two ways. first", "two ways. first efficient", "ways. first efficient plasmin", "first efficient plasmin activation", "efficient plasmin activation and fibrinolysis", "plasmin activation and fibrinolysis occur", "activation and fibrinolysis occur only", "and fibrinolysis occur only in", "fibrinolysis occur only in complexes", "occur only in complexes formed", "only in complexes formed at", "in complexes formed at the", "complexes formed at the clot", "formed at the clot surface", "at the clot surface or", "the clot surface or on", "clot surface or on a", "surface or on a cell", "or on a cell membrane", "cell membrane proteins", "membrane proteins free", "proteins free in the blood", "free in the blood are", "in the blood are inefficient", "the blood are inefficient catalysts", "blood are inefficient catalysts and", "are inefficient catalysts and are", "inefficient catalysts and are rapidly", "catalysts and are rapidly inactivated.", "and are rapidly inactivated. second", "rapidly inactivated. second both", "inactivated. second both plasminogen", "second both plasminogen activators", "both plasminogen activators and plasmin", "plasminogen activators and plasmin itself", "activators and plasmin itself are", "and plasmin itself are inactivated", "plasmin itself are inactivated by", "itself are inactivated by specific", "are inactivated by specific serpins", "by specific serpins proteins", "specific serpins proteins that", "serpins proteins that bind", "proteins that bind to serine", "that bind to serine proteases", "bind to serine proteases to", "to serine proteases to form", "serine proteases to form stable", "to form stable enzymatically", "form stable enzymatically inactive", "stable enzymatically inactive complexes", "enzymatically inactive complexes kohler", "inactive complexes kohler and", "complexes kohler and grant", "kohler and grant 2000 .
              these", "and grant 2000 .
              these events", "grant 2000 .
              these events are", "2000 .
              these events are outlined", ".
              these events are outlined in", "events are outlined in the", "are outlined in the drawing:", "outlined in the drawing: black", "in the drawing: black arrows", "the drawing: black arrows connect", "drawing: black arrows connect the", "black arrows connect the substrates", "connect the substrates inputs", "substrates inputs and", "products outputs of", "outputs of individual reactions", "of individual reactions and", "individual reactions and blue", "reactions and blue lines", "and blue lines connect output", "blue lines connect output activated", "lines connect output activated enzymes", "connect output activated enzymes to", "output activated enzymes to the", "activated enzymes to the other", "enzymes to the other reactions", "to the other reactions that", "the other reactions that they", "other reactions that they catalyze." ] }, { "record_id": "GLY_000594_1_1127", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75892", "r hsa", "hsa 75892", "r hsa 75892" ] }, { "record_id": "GLY_000594_1_1127", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "platelet adhesion", "adhesion to", "to exposed", "exposed collagen", "platelet adhesion to", "adhesion to exposed", "to exposed collagen", "platelet adhesion to exposed", "adhesion to exposed collagen", "platelet adhesion to exposed collagen", "initiation of", "of platelet", "adhesion is", "is the", "the first", "first step", "step in", "in the", "the formation", "formation of", "of the", "the platelet", "platelet plug.", "plug. circulating", "circulating platelets", "platelets are", "are arrested", "arrested and", "and subsequently", "subsequently activated", "activated by", "by exposed", "collagen and", "and von", "von willebrand", "willebrand factor", "vwf .", ". it", "it is", "is not", "not entirely", "entirely clear", "clear which", "which type", "type of", "of collagen", "collagen is", "is responsible", "responsible for", "for adhesion", "adhesion and", "and activation", "collagen types", "types i", "i and", "and iii", "iii are", "are abundant", "abundant in", "in vascular", "vascular epithelia", "epithelia but", "but several", "several other", "other types", "types including", "including iv", "iv are", "are present", "farndale rw", "rw 2006", "2006 .", ". several", "several collagen", "collagen binding", "binding proteins", "proteins are", "are expressed", "expressed on", "on platelets", "including integrin", "integrin alpha2", "alpha2 beta1", "\u03b12\u03b21 or", "or itga2:itgb1", "and gpiv.", "gpiv. itga2:itgb1", "known on", "on leukocytes", "leukocytes as", "as vla", "vla 2", "the major", "major platelet", "platelet collagen", "collagen receptor", "kunicki tj", "tj et", "et al.", "1988 .", ". itga2:itgb1", "requires mg2+", "mg2+ to", "to interact", "interact with", "with collagen.", "collagen. the", "the activation", "activation of", "of itga2:itgb1", "is modulated", "modulated by", "by the", "of integrin", "integrin alphaiib", "alphaiib beta3", "\u03b1iib\u03b23 or", "or itga2b:itgb3", "which functions", "functions as", "as a", "a platelet", "platelet receptor", "receptor for", "for fibrinogen", "fibrinogen and", "and vwf", "van de", "de walle", "walle gr", "gr et", "2007 .", ". the", "the i", "i domain", "domain of", "of \u03b12", "subunit binds", "binds a", "a collagen", "collagen motif", "motif with", "with the", "the sequence", "sequence gly", "gly phe", "phe hyp", "hyp gly", "gly glu", "glu arg", "emsley j", "j et", "2000 .", ". binding", "binding of", "collagen to", "to itga2:itgb1", "generates intracellular", "intracellular signals", "signals that", "that contribute", "contribute to", "to platelet", "platelet activation.", "activation. these", "these interactions", "interactions facilitate", "facilitate the", "the engagement", "engagement of", "the lower", "lower affinity", "affinity collagen", "tsuji m", "m et", "the key", "key receptor", "receptor involved", "involved in", "in collagen", "collagen induced", "induced platelet", "activation. the", "the gpvi", "gpvi receptor", "receptor is", "is a", "a complex", "complex of", "gpvi protein", "protein with", "with a", "a dimer", "dimer of", "of fc", "fc epsilon", "epsilon r1", "r1 gamma", "fceri gamma", "gamma .", "the src", "src family", "family kinases", "kinases fyn", "fyn and", "and lyn", "lyn constitutively", "constitutively associate", "associate with", "the gpvi:fcerigamma", "gpvi:fcerigamma complex", "complex in", "in platelets", "platelets and", "and initiate", "initiate platelet", "platelet activation", "activation through", "through phosphorylation", "phosphorylation of", "the immunoreceptor", "immunoreceptor tyrosine", "tyrosine based", "based activation", "activation motif", "in fceri", "leading to", "to binding", "binding and", "the tyrosine", "tyrosine kinase", "kinase syk.", "syk. downstream", "downstream of", "of syk", "a series", "series of", "of adapter", "adapter molecules", "molecules and", "and effectors", "effectors lead", "lead to", "activation. vwf", "vwf circulates", "circulates in", "in plasma", "plasma as", "a multimeric", "multimeric molecule", "molecule that", "that senses", "senses hydrodynamic", "hydrodynamic shear", "shear forces", "forces in", "the bloodstream", "reininger aj", "aj 2008", "mojzisch a", "a &", "& brehm", "brehm ma", "ma 2021", "2021 .", ". upon", "upon vascular", "vascular injury", "circulating vwf", "vwf binds", "binds to", "to subendothelial", "subendothelial collagen", "which becomes", "becomes exposed", "exposed to", "to the", "the flowing", "flowing blood", "bergmeier w", "w &", "& hynes", "hynes ro", "ro 2012", "colace tv", "tv &", "& diamond", "diamond sl", "sl 2013", "2013 .", "upon binding", "binding to", "to collagen", "vwf becomes", "becomes anchored", "anchored to", "the damaged", "damaged surface.", "surface. shear", "forces then", "then induce", "induce conformational", "conformational changes", "changes to", "to mechanosensitive", "mechanosensitive vwf", "vwf causing", "causing the", "the bound", "bound vwf", "vwf to", "to stretch", "stretch and", "and unfold", "li f", "f et", "schneider sw", "sw et", "fu h", "h et", "2017 .", ". vwf", "vwf unfolding", "unfolding leads", "leads to", "to exposure", "exposure of", "the a1", "a1 domain", "domain to", "to allow", "allow binding", "to glycoprotein", "glycoprotein ib", "ib \u03b1", "encoded by", "by gp1ba", "a subunit", "subunit of", "platelet surface", "surface gpib:ix:v", "gpib:ix:v complex", "dumas jj", "jj et", "ju l", "l et", ". shear", "shear induced", "induced aggregation", "aggregation is", "is achieved", "achieved when", "when vwf", "vwf interacts", "interacts both", "both with", "with exposed", "and platelets", "platelets to", "to initiate", "to vascular", "injury sites.", "sites. the", "the interaction", "interaction between", "between vwf", "vwf and", "and gpib", "gpib is", "is regulated", "regulated by", "by shear", "shear force", "an increase", "increase in", "the shear", "shear stress", "stress results", "results in", "in a", "a corresponding", "corresponding increase", "the affinity", "affinity of", "of vwf", "vwf for", "for gpib.", "initiation of platelet", "of platelet adhesion", "platelet adhesion is", "adhesion is the", "is the first", "the first step", "first step in", "step in the", "in the formation", "the formation of", "formation of the", "of the platelet", "the platelet plug.", "platelet plug. circulating", "plug. circulating platelets", "circulating platelets are", "platelets are arrested", "are arrested and", "arrested and subsequently", "and subsequently activated", "subsequently activated by", "activated by exposed", "by exposed collagen", "exposed collagen and", "collagen and von", "and von willebrand", "von willebrand factor", "factor vwf", "vwf . it", ". it is", "it is not", "is not entirely", "not entirely clear", "entirely clear which", "clear which type", "which type of", "type of collagen", "of collagen is", "collagen is responsible", "is responsible for", "responsible for adhesion", "for adhesion and", "adhesion and activation", "activation collagen", "collagen types i", "types i and", "i and iii", "and iii are", "iii are abundant", "are abundant in", "abundant in vascular", "in vascular epithelia", "vascular epithelia but", "epithelia but several", "but several other", "several other types", "other types including", "types including iv", "including iv are", "iv are present", "present farndale", "farndale rw 2006", "rw 2006 .", "2006 . several", ". several collagen", "several collagen binding", "collagen binding proteins", "binding proteins are", "proteins are expressed", "are expressed on", "expressed on platelets", "platelets including", "including integrin alpha2", "integrin alpha2 beta1", "beta1 \u03b12\u03b21", "\u03b12\u03b21 or itga2:itgb1", "gpvi and", "and gpiv. itga2:itgb1", "itga2:itgb1 known", "known on leukocytes", "on leukocytes as", "leukocytes as vla", "as vla 2", "2 is", "is the major", "the major platelet", "major platelet collagen", "platelet collagen receptor", "receptor kunicki", "kunicki tj et", "tj et al.", "al. 1988", "1988 . itga2:itgb1", "itga2:itgb1 \u03b12\u03b21", "\u03b12\u03b21 requires", "requires mg2+ to", "mg2+ to interact", "to interact with", "interact with collagen.", "with collagen. the", "collagen. the activation", "the activation of", "activation of itga2:itgb1", "\u03b12\u03b21 is", "is modulated by", "modulated by the", "by the activation", "activation of integrin", "of integrin alphaiib", "integrin alphaiib beta3", "beta3 \u03b1iib\u03b23", "\u03b1iib\u03b23 or itga2b:itgb3", "which functions as", "functions as a", "as a platelet", "a platelet receptor", "platelet receptor for", "receptor for fibrinogen", "for fibrinogen and", "fibrinogen and vwf", "vwf van", "van de walle", "de walle gr", "walle gr et", "gr et al.", "al. 2007", "2007 . the", ". the i", "the i domain", "i domain of", "domain of \u03b12", "\u03b12 itga2", "itga2 subunit", "subunit binds a", "binds a collagen", "a collagen motif", "collagen motif with", "motif with the", "with the sequence", "the sequence gly", "sequence gly phe", "gly phe hyp", "phe hyp gly", "hyp gly glu", "gly glu arg", "arg emsley", "emsley j et", "j et al.", "al. 2000", "2000 . binding", ". binding of", "binding of collagen", "of collagen to", "collagen to itga2:itgb1", "\u03b12\u03b21 generates", "generates intracellular signals", "intracellular signals that", "signals that contribute", "that contribute to", "contribute to platelet", "to platelet activation.", "platelet activation. these", "activation. these interactions", "these interactions facilitate", "interactions facilitate the", "facilitate the engagement", "the engagement of", "engagement of the", "of the lower", "the lower affinity", "lower affinity collagen", "affinity collagen receptor", "receptor gpvi", "gpvi tsuji", "tsuji m et", "m et al.", "al. 1997", "the key receptor", "key receptor involved", "receptor involved in", "involved in collagen", "in collagen induced", "collagen induced platelet", "induced platelet activation.", "platelet activation. the", "activation. the gpvi", "the gpvi receptor", "gpvi receptor is", "receptor is a", "is a complex", "a complex of", "complex of the", "of the gpvi", "the gpvi protein", "gpvi protein with", "protein with a", "with a dimer", "a dimer of", "dimer of fc", "of fc epsilon", "fc epsilon r1", "epsilon r1 gamma", "gamma fceri", "fceri gamma .", "gamma . the", ". the src", "the src family", "src family kinases", "family kinases fyn", "kinases fyn and", "fyn and lyn", "and lyn constitutively", "lyn constitutively associate", "constitutively associate with", "associate with the", "with the gpvi:fcerigamma", "the gpvi:fcerigamma complex", "gpvi:fcerigamma complex in", "complex in platelets", "in platelets and", "platelets and initiate", "and initiate platelet", "initiate platelet activation", "platelet activation through", "activation through phosphorylation", "through phosphorylation of", "phosphorylation of the", "of the immunoreceptor", "the immunoreceptor tyrosine", "immunoreceptor tyrosine based", "tyrosine based activation", "based activation motif", "motif itam", "itam in", "in fceri gamma", "gamma leading", "leading to binding", "to binding and", "binding and activation", "and activation of", "activation of the", "of the tyrosine", "the tyrosine kinase", "tyrosine kinase syk.", "kinase syk. downstream", "syk. downstream of", "downstream of syk", "syk a", "a series of", "series of adapter", "of adapter molecules", "adapter molecules and", "molecules and effectors", "and effectors lead", "effectors lead to", "lead to platelet", "platelet activation. vwf", "activation. vwf circulates", "vwf circulates in", "circulates in plasma", "in plasma as", "plasma as a", "as a multimeric", "a multimeric molecule", "multimeric molecule that", "molecule that senses", "that senses hydrodynamic", "senses hydrodynamic shear", "hydrodynamic shear forces", "shear forces in", "forces in the", "in the bloodstream", "bloodstream reininger", "reininger aj 2008", "2008 mojzisch", "mojzisch a &", "a & brehm", "& brehm ma", "brehm ma 2021", "ma 2021 .", "2021 . upon", ". upon vascular", "upon vascular injury", "injury circulating", "circulating vwf binds", "vwf binds to", "binds to subendothelial", "to subendothelial collagen", "collagen which", "which becomes exposed", "becomes exposed to", "exposed to the", "to the flowing", "the flowing blood", "blood bergmeier", "bergmeier w &", "w & hynes", "& hynes ro", "hynes ro 2012", "2012 colace", "colace tv &", "tv & diamond", "& diamond sl", "diamond sl 2013", "sl 2013 .", "2013 . upon", ". upon binding", "upon binding to", "binding to collagen", "collagen vwf", "vwf becomes anchored", "becomes anchored to", "anchored to the", "to the damaged", "the damaged surface.", "damaged surface. shear", "surface. shear forces", "shear forces then", "forces then induce", "then induce conformational", "induce conformational changes", "conformational changes to", "changes to mechanosensitive", "to mechanosensitive vwf", "mechanosensitive vwf causing", "vwf causing the", "causing the bound", "the bound vwf", "bound vwf to", "vwf to stretch", "to stretch and", "stretch and unfold", "unfold li", "li f et", "f et al.", "al. 2004", "2004 schneider", "schneider sw et", "sw et al.", "2007 fu", "fu h et", "h et al.", "al. 2017", "2017 . vwf", ". vwf unfolding", "vwf unfolding leads", "unfolding leads to", "leads to exposure", "to exposure of", "exposure of the", "of the a1", "the a1 domain", "a1 domain to", "domain to allow", "to allow binding", "allow binding to", "binding to glycoprotein", "to glycoprotein ib", "glycoprotein ib \u03b1", "\u03b1 gpib\u03b1", "gpib\u03b1 encoded", "encoded by gp1ba", "a subunit of", "subunit of the", "the platelet surface", "platelet surface gpib:ix:v", "surface gpib:ix:v complex", "complex dumas", "dumas jj et", "jj et al.", "2004 ju", "ju l et", "l et al.", "al. 2013", "2013 . shear", ". shear induced", "shear induced aggregation", "induced aggregation is", "aggregation is achieved", "is achieved when", "achieved when vwf", "when vwf interacts", "vwf interacts both", "interacts both with", "both with exposed", "with exposed collagen", "collagen and platelets", "and platelets to", "platelets to initiate", "to initiate platelet", "initiate platelet adhesion", "adhesion to vascular", "to vascular injury", "vascular injury sites.", "injury sites. the", "sites. the interaction", "the interaction between", "interaction between vwf", "between vwf and", "vwf and gpib", "and gpib is", "gpib is regulated", "is regulated by", "regulated by shear", "by shear force", "force an", "an increase in", "increase in the", "in the shear", "the shear stress", "shear stress results", "stress results in", "results in a", "in a corresponding", "a corresponding increase", "corresponding increase in", "in the affinity", "the affinity of", "affinity of vwf", "of vwf for", "vwf for gpib.", "initiation of platelet adhesion", "of platelet adhesion is", "platelet adhesion is the", "adhesion is the first", "is the first step", "the first step in", "first step in the", "step in the formation", "in the formation of", "the formation of the", "formation of the platelet", "of the platelet plug.", "the platelet plug. circulating", "platelet plug. circulating platelets", "plug. circulating platelets are", "circulating platelets are arrested", "platelets are arrested and", "are arrested and subsequently", "arrested and subsequently activated", "and subsequently activated by", "subsequently activated by exposed", "activated by exposed collagen", "by exposed collagen and", "exposed collagen and von", "collagen and von willebrand", "and von willebrand factor", "willebrand factor vwf", "factor vwf .", "vwf . it is", ". it is not", "it is not entirely", "is not entirely clear", "not entirely clear which", "entirely clear which type", "clear which type of", "which type of collagen", "type of collagen is", "of collagen is responsible", "collagen is responsible for", "is responsible for adhesion", "responsible for adhesion and", "for adhesion and activation", "and activation collagen", "activation collagen types", "collagen types i and", "types i and iii", "i and iii are", "and iii are abundant", "iii are abundant in", "are abundant in vascular", "abundant in vascular epithelia", "in vascular epithelia but", "vascular epithelia but several", "epithelia but several other", "but several other types", "several other types including", "other types including iv", "types including iv are", "including iv are present", "are present farndale", "present farndale rw", "farndale rw 2006 .", "rw 2006 . several", "2006 . several collagen", ". several collagen binding", "several collagen binding proteins", "collagen binding proteins are", "binding proteins are expressed", "proteins are expressed on", "are expressed on platelets", "on platelets including", "platelets including integrin", "including integrin alpha2 beta1", "alpha2 beta1 \u03b12\u03b21", "beta1 \u03b12\u03b21 or", "itga2:itgb1 gpvi", "gpvi and gpiv.", "gpiv. itga2:itgb1 known", "itga2:itgb1 known on", "known on leukocytes as", "on leukocytes as vla", "leukocytes as vla 2", "vla 2 is", "2 is the", "is the major platelet", "the major platelet collagen", "major platelet collagen receptor", "collagen receptor kunicki", "receptor kunicki tj", "kunicki tj et al.", "et al. 1988", "al. 1988 .", ". itga2:itgb1 \u03b12\u03b21", "\u03b12\u03b21 requires mg2+", "requires mg2+ to interact", "mg2+ to interact with", "to interact with collagen.", "interact with collagen. the", "with collagen. the activation", "collagen. the activation of", "the activation of itga2:itgb1", "of itga2:itgb1 \u03b12\u03b21", "\u03b12\u03b21 is modulated", "is modulated by the", "modulated by the activation", "by the activation of", "the activation of integrin", "activation of integrin alphaiib", "of integrin alphaiib beta3", "alphaiib beta3 \u03b1iib\u03b23", "beta3 \u03b1iib\u03b23 or", "itga2b:itgb3 which", "which functions as a", "functions as a platelet", "as a platelet receptor", "a platelet receptor for", "platelet receptor for fibrinogen", "receptor for fibrinogen and", "for fibrinogen and vwf", "and vwf van", "vwf van de", "van de walle gr", "de walle gr et", "walle gr et al.", "et al. 2007", "al. 2007 .", "2007 . the i", ". the i domain", "the i domain of", "i domain of \u03b12", "of \u03b12 itga2", "itga2 subunit binds", "subunit binds a collagen", "binds a collagen motif", "a collagen motif with", "collagen motif with the", "motif with the sequence", "with the sequence gly", "the sequence gly phe", "sequence gly phe hyp", "gly phe hyp gly", "phe hyp gly glu", "hyp gly glu arg", "glu arg emsley", "arg emsley j", "emsley j et al.", "et al. 2000", "al. 2000 .", "2000 . binding of", ". binding of collagen", "binding of collagen to", "of collagen to itga2:itgb1", "to itga2:itgb1 \u03b12\u03b21", "\u03b12\u03b21 generates intracellular", "generates intracellular signals that", "intracellular signals that contribute", "signals that contribute to", "that contribute to platelet", "contribute to platelet activation.", "to platelet activation. these", "platelet activation. these interactions", "activation. these interactions facilitate", "these interactions facilitate the", "interactions facilitate the engagement", "facilitate the engagement of", "the engagement of the", "engagement of the lower", "of the lower affinity", "the lower affinity collagen", "lower affinity collagen receptor", "collagen receptor gpvi", "gpvi tsuji m", "tsuji m et al.", "et al. 1997", "1997 the", "the key receptor involved", "key receptor involved in", "receptor involved in collagen", "involved in collagen induced", "in collagen induced platelet", "collagen induced platelet activation.", "induced platelet activation. the", "platelet activation. the gpvi", "activation. the gpvi receptor", "the gpvi receptor is", "gpvi receptor is a", "receptor is a complex", "is a complex of", "a complex of the", "complex of the gpvi", "of the gpvi protein", "the gpvi protein with", "gpvi protein with a", "protein with a dimer", "with a dimer of", "a dimer of fc", "dimer of fc epsilon", "of fc epsilon r1", "fc epsilon r1 gamma", "r1 gamma fceri", "gamma fceri gamma", "fceri gamma . the", "gamma . the src", ". the src family", "the src family kinases", "src family kinases fyn", "family kinases fyn and", "kinases fyn and lyn", "fyn and lyn constitutively", "and lyn constitutively associate", "lyn constitutively associate with", "constitutively associate with the", "associate with the gpvi:fcerigamma", "with the gpvi:fcerigamma complex", "the gpvi:fcerigamma complex in", "gpvi:fcerigamma complex in platelets", "complex in platelets and", "in platelets and initiate", "platelets and initiate platelet", "and initiate platelet activation", "initiate platelet activation through", "platelet activation through phosphorylation", "activation through phosphorylation of", "through phosphorylation of the", "phosphorylation of the immunoreceptor", "of the immunoreceptor tyrosine", "the immunoreceptor tyrosine based", "immunoreceptor tyrosine based activation", "tyrosine based activation motif", "activation motif itam", "itam in fceri", "fceri gamma leading", "gamma leading to", "leading to binding and", "to binding and activation", "binding and activation of", "and activation of the", "activation of the tyrosine", "of the tyrosine kinase", "the tyrosine kinase syk.", "tyrosine kinase syk. downstream", "kinase syk. downstream of", "syk. downstream of syk", "of syk a", "syk a series", "a series of adapter", "series of adapter molecules", "of adapter molecules and", "adapter molecules and effectors", "molecules and effectors lead", "and effectors lead to", "effectors lead to platelet", "lead to platelet activation.", "to platelet activation. vwf", "platelet activation. vwf circulates", "activation. vwf circulates in", "vwf circulates in plasma", "circulates in plasma as", "in plasma as a", "plasma as a multimeric", "as a multimeric molecule", "a multimeric molecule that", "multimeric molecule that senses", "molecule that senses hydrodynamic", "that senses hydrodynamic shear", "senses hydrodynamic shear forces", "hydrodynamic shear forces in", "shear forces in the", "forces in the bloodstream", "the bloodstream reininger", "bloodstream reininger aj", "aj 2008 mojzisch", "2008 mojzisch a", "mojzisch a & brehm", "a & brehm ma", "& brehm ma 2021", "brehm ma 2021 .", "ma 2021 . upon", "2021 . upon vascular", ". upon vascular injury", "vascular injury circulating", "injury circulating vwf", "circulating vwf binds to", "vwf binds to subendothelial", "binds to subendothelial collagen", "subendothelial collagen which", "collagen which becomes", "which becomes exposed to", "becomes exposed to the", "exposed to the flowing", "to the flowing blood", "flowing blood bergmeier", "blood bergmeier w", "bergmeier w & hynes", "w & hynes ro", "& hynes ro 2012", "ro 2012 colace", "2012 colace tv", "colace tv & diamond", "tv & diamond sl", "& diamond sl 2013", "diamond sl 2013 .", "sl 2013 . upon", "2013 . upon binding", ". upon binding to", "upon binding to collagen", "to collagen vwf", "collagen vwf becomes", "vwf becomes anchored to", "becomes anchored to the", "anchored to the damaged", "to the damaged surface.", "the damaged surface. shear", "damaged surface. shear forces", "surface. shear forces then", "shear forces then induce", "forces then induce conformational", "then induce conformational changes", "induce conformational changes to", "conformational changes to mechanosensitive", "changes to mechanosensitive vwf", "to mechanosensitive vwf causing", "mechanosensitive vwf causing the", "vwf causing the bound", "causing the bound vwf", "the bound vwf to", "bound vwf to stretch", "vwf to stretch and", "to stretch and unfold", "and unfold li", "unfold li f", "li f et al.", "et al. 2004", "2004 schneider sw", "schneider sw et al.", "2007 fu h", "fu h et al.", "et al. 2017", "al. 2017 .", "2017 . vwf unfolding", ". vwf unfolding leads", "vwf unfolding leads to", "unfolding leads to exposure", "leads to exposure of", "to exposure of the", "exposure of the a1", "of the a1 domain", "the a1 domain to", "a1 domain to allow", "domain to allow binding", "to allow binding to", "allow binding to glycoprotein", "binding to glycoprotein ib", "to glycoprotein ib \u03b1", "ib \u03b1 gpib\u03b1", "gpib\u03b1 encoded by", "gp1ba a", "a subunit of the", "subunit of the platelet", "of the platelet surface", "the platelet surface gpib:ix:v", "platelet surface gpib:ix:v complex", "gpib:ix:v complex dumas", "complex dumas jj", "dumas jj et al.", "2004 ju l", "ju l et al.", "et al. 2013", "al. 2013 .", "2013 . shear induced", ". shear induced aggregation", "shear induced aggregation 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"shear stress results in", "stress results in a", "results in a corresponding", "in a corresponding increase", "a corresponding increase in", "corresponding increase in the", "increase in the affinity", "in the affinity of", "the affinity of vwf", "affinity of vwf for", "of vwf for gpib.", "initiation of platelet adhesion is", "of platelet adhesion is the", "platelet adhesion is the first", "adhesion is the first step", "is the first step in", "the first step in the", "first step in the formation", "step in the formation of", "in the formation of the", "the formation of the platelet", "formation of the platelet plug.", "of the platelet plug. circulating", "the platelet plug. circulating platelets", "platelet plug. circulating platelets are", "plug. circulating platelets are arrested", "circulating platelets are arrested and", "platelets are arrested and subsequently", "are arrested and subsequently activated", "arrested and subsequently activated by", "and subsequently activated by exposed", "subsequently activated by exposed collagen", "activated by exposed collagen and", "by exposed collagen and von", "exposed collagen and von willebrand", "collagen and von willebrand factor", "von willebrand factor vwf", "willebrand factor vwf .", "factor vwf . it", "vwf . it is not", ". it is not entirely", "it is not entirely clear", "is not entirely clear which", "not entirely clear which type", "entirely clear which type of", "clear which type of collagen", "which type of collagen is", "type of collagen is responsible", "of collagen is responsible for", "collagen is responsible for adhesion", "is responsible for adhesion and", "responsible for adhesion and activation", "adhesion and activation collagen", "and activation collagen types", "activation collagen types i", "collagen types i and iii", "types i and iii are", "i and iii are abundant", "and iii are abundant in", "iii are abundant in vascular", "are abundant in vascular epithelia", "abundant in vascular epithelia but", "in vascular epithelia but several", "vascular epithelia but several other", "epithelia but several other types", "but several other types including", "several other types including iv", "other types including iv are", "types including iv are present", "iv are present farndale", "are present farndale rw", "present farndale rw 2006", "farndale rw 2006 . several", "rw 2006 . several collagen", "2006 . several collagen binding", ". several collagen binding proteins", "several collagen binding proteins are", "collagen binding proteins are expressed", "binding proteins are expressed on", "proteins are expressed on platelets", "expressed on platelets including", "on platelets including integrin", "platelets including integrin alpha2", "integrin alpha2 beta1 \u03b12\u03b21", "alpha2 beta1 \u03b12\u03b21 or", "beta1 \u03b12\u03b21 or itga2:itgb1", "or itga2:itgb1 gpvi", "gpvi and gpiv. itga2:itgb1", "and gpiv. itga2:itgb1 known", "gpiv. itga2:itgb1 known on", "itga2:itgb1 known on leukocytes", "known on leukocytes as vla", "on leukocytes as vla 2", "as vla 2 is", "vla 2 is the", "2 is the major", "is the major platelet collagen", "the major platelet collagen receptor", "platelet collagen receptor kunicki", "collagen receptor kunicki tj", "receptor kunicki tj et", "tj et al. 1988", "et al. 1988 .", "al. 1988 . itga2:itgb1", "1988 . itga2:itgb1 \u03b12\u03b21", "itga2:itgb1 \u03b12\u03b21 requires", "\u03b12\u03b21 requires mg2+ to", "requires mg2+ to interact with", "mg2+ to interact with collagen.", "to interact with collagen. the", "interact with collagen. the activation", "with collagen. the activation of", "collagen. the activation of itga2:itgb1", "activation of itga2:itgb1 \u03b12\u03b21", "itga2:itgb1 \u03b12\u03b21 is", "\u03b12\u03b21 is modulated by", "is modulated by the activation", "modulated by the activation of", "by the activation of integrin", "the activation of integrin alphaiib", "activation of integrin alphaiib beta3", "integrin alphaiib beta3 \u03b1iib\u03b23", "alphaiib beta3 \u03b1iib\u03b23 or", "beta3 \u03b1iib\u03b23 or itga2b:itgb3", "or itga2b:itgb3 which", "itga2b:itgb3 which functions", "which functions as a platelet", "functions as a platelet receptor", "as a platelet receptor for", "a platelet receptor for fibrinogen", "platelet receptor for fibrinogen and", "receptor for fibrinogen and vwf", "fibrinogen and vwf van", "and vwf van de", "vwf van de walle", "van de walle gr et", "de walle gr et al.", "gr et al. 2007", "et al. 2007 .", "al. 2007 . the", "2007 . the i domain", ". the i domain of", "the i domain of \u03b12", "domain of \u03b12 itga2", "\u03b12 itga2 subunit", "itga2 subunit binds a", "subunit binds a collagen motif", "binds a collagen motif with", "a collagen motif with the", "collagen motif with the sequence", "motif with the sequence gly", "with the sequence gly phe", "the sequence gly phe hyp", "sequence gly phe hyp gly", "gly phe hyp gly glu", "phe hyp gly glu arg", "gly glu arg emsley", "glu arg emsley j", "arg emsley j et", "j et al. 2000", "et al. 2000 .", "al. 2000 . binding", "2000 . binding of collagen", ". binding of collagen to", "binding of collagen to itga2:itgb1", "collagen to itga2:itgb1 \u03b12\u03b21", "itga2:itgb1 \u03b12\u03b21 generates", "\u03b12\u03b21 generates intracellular signals", "generates intracellular signals that contribute", "intracellular signals that contribute to", "signals that contribute to platelet", "that contribute to platelet activation.", "contribute to platelet activation. these", "to platelet activation. these interactions", "platelet activation. these interactions facilitate", "activation. these interactions facilitate the", "these interactions facilitate the engagement", "interactions facilitate the engagement of", "facilitate the engagement of the", "the engagement of the lower", "engagement of the lower affinity", "of the lower affinity collagen", "the lower affinity collagen receptor", "affinity collagen receptor gpvi", "receptor gpvi tsuji", "gpvi tsuji m et", "m et al. 1997", "1997 the key", "the key receptor involved in", "key receptor involved in collagen", "receptor involved in collagen induced", "involved in collagen induced platelet", "in collagen induced platelet activation.", "collagen induced platelet activation. the", "induced platelet activation. the gpvi", "platelet activation. the gpvi receptor", "activation. the gpvi receptor is", "the gpvi receptor is a", "gpvi receptor is a complex", "receptor is a complex of", "is a complex of the", "a complex of the gpvi", "complex of the gpvi protein", "of the gpvi protein with", "the gpvi protein with a", "gpvi protein with a dimer", "protein with a dimer of", "with a dimer of fc", "a dimer of fc epsilon", "dimer of fc epsilon r1", "of fc epsilon r1 gamma", "epsilon r1 gamma fceri", "r1 gamma fceri gamma", "gamma fceri gamma .", "fceri gamma . the src", "gamma . the src family", ". the src family kinases", "the src family kinases fyn", "src family kinases fyn and", "family kinases fyn and lyn", "kinases fyn and lyn constitutively", "fyn and lyn constitutively associate", "and lyn constitutively associate with", "lyn constitutively associate with the", "constitutively associate with the gpvi:fcerigamma", "associate with the gpvi:fcerigamma complex", "with the gpvi:fcerigamma complex in", "the gpvi:fcerigamma complex in platelets", "gpvi:fcerigamma complex in platelets and", "complex in platelets and initiate", "in platelets and initiate platelet", "platelets and initiate platelet activation", "and initiate platelet activation through", "initiate platelet activation through phosphorylation", "platelet activation through phosphorylation of", "activation through phosphorylation of the", "through phosphorylation of the immunoreceptor", "phosphorylation of the immunoreceptor tyrosine", "of the immunoreceptor tyrosine based", "the immunoreceptor tyrosine based activation", "immunoreceptor tyrosine based activation motif", "based activation motif itam", "motif itam in", "itam in fceri gamma", "in fceri gamma leading", "fceri gamma leading to", "gamma leading to binding", "leading to binding and activation", "to binding and activation of", "binding and activation of the", "and activation of the tyrosine", "activation of the tyrosine kinase", "of the tyrosine kinase syk.", "the tyrosine kinase syk. downstream", "tyrosine kinase syk. downstream of", "kinase syk. downstream of syk", "downstream of syk a", "of syk a series", "syk a series of", "a series of adapter molecules", "series of adapter molecules and", "of adapter molecules and effectors", "adapter molecules and effectors lead", "molecules and effectors lead to", "and effectors lead to platelet", "effectors lead to platelet activation.", "lead to platelet activation. vwf", "to platelet activation. vwf circulates", "platelet activation. vwf circulates in", "activation. vwf circulates in plasma", "vwf circulates in plasma as", "circulates in plasma as a", "in plasma as a multimeric", "plasma as a multimeric molecule", "as a multimeric molecule that", "a multimeric molecule that senses", "multimeric molecule that senses hydrodynamic", "molecule that senses hydrodynamic shear", "that senses hydrodynamic shear forces", "senses hydrodynamic shear forces in", "hydrodynamic shear forces in the", "shear forces in the bloodstream", "in the bloodstream reininger", "the bloodstream reininger aj", "bloodstream reininger aj 2008", "reininger aj 2008 mojzisch", "aj 2008 mojzisch a", "2008 mojzisch a &", "mojzisch a & brehm ma", "a & brehm ma 2021", "& brehm ma 2021 .", "brehm ma 2021 . upon", "ma 2021 . upon vascular", "2021 . upon vascular injury", "upon vascular injury circulating", "vascular injury circulating vwf", "injury circulating vwf binds", "circulating vwf binds to subendothelial", "vwf binds to subendothelial collagen", "to subendothelial collagen which", "subendothelial collagen which becomes", "collagen which becomes exposed", "which becomes exposed to the", "becomes exposed to the flowing", "exposed to the flowing blood", "the flowing blood bergmeier", "flowing blood bergmeier w", "blood bergmeier w &", "bergmeier w & hynes ro", "w & hynes ro 2012", "hynes ro 2012 colace", "ro 2012 colace tv", "2012 colace tv &", "colace tv & diamond sl", "tv & diamond sl 2013", "& diamond sl 2013 .", "diamond sl 2013 . upon", "sl 2013 . upon binding", "2013 . upon binding to", ". upon binding to collagen", "binding to collagen vwf", "to collagen vwf becomes", "collagen vwf becomes anchored", "vwf becomes anchored to the", "becomes anchored to the damaged", "anchored to the damaged surface.", "to the damaged surface. shear", "the damaged surface. shear forces", "damaged surface. shear forces then", "surface. shear forces then induce", "shear forces then induce conformational", "forces then induce conformational changes", "then induce conformational changes to", "induce conformational changes to mechanosensitive", "conformational changes to mechanosensitive vwf", "changes to mechanosensitive vwf causing", "to mechanosensitive vwf causing the", "mechanosensitive vwf causing the bound", "vwf causing the bound vwf", "causing the bound vwf to", "the bound vwf to stretch", "bound vwf to stretch and", "vwf to stretch and unfold", "stretch and unfold li", "and unfold li f", "unfold li f et", "f et al. 2004", "al. 2004 schneider", "2004 schneider sw et", "sw et al. 2007", "al. 2007 fu", "2007 fu h et", "h et al. 2017", "et al. 2017 .", "al. 2017 . vwf", "2017 . vwf unfolding leads", ". vwf unfolding leads to", "vwf unfolding leads to exposure", "unfolding leads to exposure of", "leads to exposure of the", "to exposure of the a1", "exposure of the a1 domain", "of the a1 domain to", "the a1 domain to allow", "a1 domain to allow binding", "domain to allow binding to", "to allow binding to glycoprotein", "allow binding to glycoprotein ib", "binding to glycoprotein ib \u03b1", "glycoprotein ib \u03b1 gpib\u03b1", "\u03b1 gpib\u03b1 encoded", "gpib\u03b1 encoded by gp1ba", "by gp1ba a", "gp1ba a subunit", "a subunit of the platelet", "subunit of the platelet surface", "of the platelet surface gpib:ix:v", "the platelet surface gpib:ix:v complex", "surface gpib:ix:v complex dumas", "gpib:ix:v complex dumas jj", "complex dumas jj et", "jj et al. 2004", "al. 2004 ju", "2004 ju l et", "l et al. 2013", "et al. 2013 .", "al. 2013 . shear", "2013 . shear induced aggregation", ". shear induced aggregation is", "shear induced aggregation is achieved", "induced aggregation is achieved when", "aggregation is achieved when vwf", "is achieved when vwf interacts", "achieved when vwf interacts both", "when vwf interacts both with", "vwf interacts both with exposed", "interacts both with exposed collagen", "both with exposed collagen and", "with exposed collagen and platelets", "exposed collagen and platelets to", "collagen and platelets to initiate", "and platelets to initiate platelet", "platelets to initiate platelet adhesion", "to initiate platelet adhesion to", "initiate platelet adhesion to vascular", "platelet adhesion to vascular injury", "adhesion to vascular injury sites.", "to vascular injury sites. the", "vascular injury sites. the interaction", "injury sites. the interaction between", "sites. the interaction between vwf", "the interaction between vwf and", "interaction between vwf and gpib", "between vwf and gpib is", "vwf and gpib is regulated", "and gpib is regulated by", "gpib is regulated by shear", "is regulated by shear force", "by shear force an", "shear force an increase", "force an increase in", "an increase in the shear", "increase in the shear stress", "in the shear stress results", "the shear stress results in", "shear stress results in a", "stress results in a corresponding", "results in a corresponding increase", "in a corresponding increase in", "a corresponding increase in the", "corresponding increase in the affinity", "increase in the affinity of", "in the affinity of vwf", "the affinity of vwf for", "affinity of vwf for gpib." ] }, { "record_id": "GLY_000594_1_1128", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75893", "r hsa", "hsa 75893", "r hsa 75893" ] }, { "record_id": "GLY_000594_1_1128", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tnf signaling", "the inflammatory", "inflammatory cytokine", "cytokine tumor", "tumor necrosis", "necrosis factor", "factor alpha", "tnf \u03b1", "is expressed", "expressed in", "in immune", "immune and", "and nonimmune", "nonimmune cell", "cell types", "types including", "including macrophages", "t cells", "mast cells", "natural killer", "keratinocytes and", "and smooth", "smooth muscle", "muscle cells", "cells as", "as a", "a response", "response to", "to tissue", "tissue injury", "injury or", "or upon", "upon immune", "immune responses", "responses to", "to pathogenic", "pathogenic stimuli", "k\u00f6ck a.", "a. et", "et al.", "al. 1990", "dubravec db", "db et", "walsh lj", "lj et", "al. 1991", "te velde", "velde aa", "aa et", "imaizumi t", "t et", "al. 2000", "2000 .", ". tnf", "\u03b1 interacts", "interacts with", "with two", "two receptors", "namely tnf", "tnf receptor", "receptor 1", "and tnf", "receptor 2", "tnfr2 .", ". activation", "activation of", "of tnfr1", "tnfr1 can", "can trigger", "trigger multiple", "multiple signal", "signal transduction", "transduction pathways", "pathways inducing", "inducing inflammation", "survival or", "or cell", "cell death", "ward c", "c et", "al. 1999", "micheau o", "o and", "and tschopp", "tschopp j", "j 2003", "widera d", "d et", "al. 2006", "2006 .", ". whether", "whether a", "a tnf", "\u03b1 stimulated", "stimulated cell", "cell will", "will survive", "survive or", "or die", "die is", "is dependent", "dependent on", "on autocrine/paracrine", "autocrine/paracrine signals", "and on", "on the", "the cellular", "cellular context.

              tnf", "context.

              tnf binding", "binding to", "to tnfr1", "tnfr1 results", "results initially", "initially in", "in the", "the formation", "formation of", "of complex", "complex i", "i that", "that consists", "consists of", "tnfr1 associated", "associated death", "death domain", "receptor associated", "associated factor", "factor 2", "receptor interacting", "interacting serin/threonine", "serin/threonine protein", "protein kinase", "kinase 1", "and e3", "e3 ubiquitin", "ubiquitin ligases", "ligases birc2", "birc2 birc3", "ciap1/2 cellular", "cellular inhibitor", "inhibitor of", "of apoptosis", "and lubac", "2003 .", ". the", "the conjugation", "conjugation of", "of ubiquitin", "ubiquitin chains", "chains by", "by birc2/3", "birc2/3 and", "composed of", "of hoip", "hoil 1", "1 and", "and sharpin", "to ripk1", "ripk1 allows", "allows further", "further recruitment", "recruitment and", "and activation", "of the", "the tak1", "also known", "known as", "as mitogen", "mitogen activated", "activated protein", "kinase kinase", "kinase 7", "complex and", "and i\u03bab", "i\u03bab kinase", "complex. tak1", "tak1 and", "and ikk", "ikk phosphorylate", "phosphorylate ripk1", "ripk1 to", "to limit", "limit its", "its cytotoxic", "cytotoxic activity", "and activate", "activate both", "both nuclear", "nuclear factor", "factor kappa\u2010light\u2010chain\u2010enhancer", "kappa\u2010light\u2010chain\u2010enhancer of", "of activated", "activated b", "b cells", "and mitogen\u2010activated", "mitogen\u2010activated protein", "kinase signaling", "signaling pathways", "pathways promoting", "promoting cell", "cell survival", "survival by", "by induction", "induction of", "of anti", "anti apoptotic", "apoptotic proteins", "proteins such", "such as", "as birc", "cellular flice", "fadd like", "like il", "il 1\u03b2", "1\u03b2 converting", "converting enzyme", "like inhibitory", "inhibitory protein", "and secretion", "secretion of", "of pro", "pro inflammatory", "inflammatory cytokines", "tnf and", "and il", "il 6", "6 .", ". when", "when the", "the survival", "survival pathway", "pathway is", "is inhibited", "the tradd:traf2:ripk1", "tradd:traf2:ripk1 detaches", "detaches from", "from the", "the membrane", "membrane bound", "bound tnfr1", "tnfr1 signaling", "signaling complex", "and recruits", "recruits fas", "fas associated", "domain containing", "containing protein", "and procaspase", "procaspase 8", "as complex", "complex ii", "ii .", ". once", "once recruited", "recruited to", "to fadd", "multiple procaspase", "8 molecules", "molecules interact", "interact via", "via their", "their tandem", "tandem death", "death effector", "effector domains", "thereby facilitating", "facilitating both", "both proximity", "proximity induced", "induced dimerization", "dimerization and", "and proteolytic", "proteolytic cleavage", "cleavage of", "of procaspase", "which are", "are required", "required for", "for initiation", "initiation of", "of apoptotic", "apoptotic cell", "hughes ma", "ma et", "al. 2009", "oberst a", "a et", "al. 2010", "2010 .", "when caspase", "caspase activity", "activity is", "inhibited under", "under certain", "certain pathophysiological", "pathophysiological conditions", "expression of", "of caspase", "caspase 8", "8 inhibitory", "inhibitory proteins", "as crma", "crma and", "and vica", "vica after", "after infection", "infection with", "with cowpox", "cowpox virus", "virus or", "or cmv", "or by", "by pharmacological", "pharmacological agents", "deubiquitinated ripk1", "ripk1 is", "is physically", "physically and", "and functionally", "functionally engaged", "engaged by", "by its", "its homolog", "homolog ripk3", "ripk3 leading", "leading to", "to formation", "the necrosome", "a necroptosis", "necroptosis inducing", "inducing complex", "complex consisting", "consisting of", "of ripk1", "ripk1 and", "and ripk3", "tewari m", "m &", "& dixit", "dixit vm", "vm 1995", "fliss pm", "pm &", "& brune", "brune w", "w 2012", "sawai h", "h 2013", "moquin dm", "dm et", "al. 2013", "kalai m", "m et", "al. 2002", "cho ys", "ys et", "he s", "s et", "zhang dw", "dw et", "2009 .", ". within", "within the", "the complex", "ii procaspase", "8 can", "can also", "also form", "form heterodimers", "heterodimers with", "with cflip", "cflip isoforms", "flip long", "and flip", "flip short", "are encoded", "encoded by", "by the", "the nfkappab", "nfkappab target", "target gene", "gene cflar", "irmler m", "al. 1997", "boatright km", "km et", "al. 2004", "yu jw", "jw et", "pop c", "al. 2011", "2011 .", ". flip", "flip s", "appears to", "to act", "act purely", "purely as", "as an", "an antagonist", "antagonist of", "8 activity", "activity blocking", "blocking apoptotic", "apoptotic but", "but promoting", "promoting necroptotic", "necroptotic cell", "the regulatory", "regulatory function", "function of", "of flip", "flip l", "has been", "been found", "found to", "to differ", "differ depending", "depending on", "on its", "its expression", "expression levels.", "levels. flip", "was shown", "shown to", "to inhibit", "inhibit death", "death receptor", "mediated apoptosis", "apoptosis only", "only when", "when expressed", "expressed at", "at high", "high levels", "while low", "low cell", "cell levels", "levels of", "enhanced dr", "dr signaling", "signaling to", "to apoptosis", "okano h", "h et", "al. 2003", "yerbes r", "r et", "al. 2016", "2016 .", ". in", "in addition", "caspase 8:flip", "8:flip l", "heterodimer activity", "activity within", "the tradd:traf2:ripk1:fadd:casp8:flip", "tradd:traf2:ripk1:fadd:casp8:flip l", "complex allowed", "allowed cleavage", "to cause", "cause the", "the dissociation", "dissociation of", "the tradd:traf2:rip1:fadd:casp8", "thereby inhibiting", "inhibiting ripk1", "ripk1 mediated", "mediated necroptosis", "2012 .", "\u03b1 can", "also activate", "activate sphingomyelinase", "as smpd2", "smpd2 3", "proteins to", "to catalyze", "catalyze hydrolysis", "hydrolysis of", "of sphingomyeline", "sphingomyeline into", "into ceramide", "adam d", "et al.1996", "adam klages", "klages s", "al. 1998", "s\u00e9gui b", "b et", "al. 2001", "2001 .", "of neutral", "neutral smpd2", "3 leads", "leads to", "to an", "an accumulation", "accumulation of", "of ceramide", "ceramide at", "at the", "the cell", "cell surface", "surface and", "and has", "has proinflammatory", "proinflammatory effects.", "effects. however", "tnf can", "activate the", "the pro", "pro apoptotic", "apoptotic acidic", "acidic smase", "smase via", "via caspase", "8 mediated", "mediated activation", "caspase 7", "7 which", "which in", "in turn", "turn proteolytically", "proteolytically cleaves", "cleaves and", "and activates", "activates the", "the 72kda", "72kda pro", "pro a", "a smase", "smase form", "edelmann b", ". ceramide", "ceramide induces", "induces anti", "anti proliferative", "proliferative and", "and pro", "apoptotic responses.", "responses. further", "ceramide can", "can be", "be converted", "converted by", "by ceramidase", "ceramidase into", "into sphingosine", "turn is", "is phosphorylated", "phosphorylated by", "by sphingosine", "sphingosine kinase", "kinase into", "sphingosine 1", "1 phosphate", "s1p .", ". s1p", "s1p exerts", "exerts the", "the opposite", "opposite biological", "biological effects", "effects to", "to ceramide", "ceramide by", "by activating", "activating cytoprotective", "cytoprotective signaling", "to promote", "promote cell", "cell growth", "growth counteracting", "counteracting the", "the apoptotic", "apoptotic stimuli", "cuvillier o", "o et", "al. 1996", "1996 .", ". thus", "\u03b1 induced", "induced tnfr1", "tnfr1 activation", "activation leads", "to divergent", "divergent intracellular", "intracellular signaling", "signaling networks", "networks with", "with extensive", "extensive cross", "cross talk", "talk between", "between the", "pro apoptotic/necroptotic", "apoptotic/necroptotic pathway", "and the", "the other", "other nfkappab", "and mapk", "mapk pathways", "pathways providing", "providing highly", "highly specific", "specific cell", "cell responses", "responses initiated", "initiated by", "by various", "various types", "types of", "of stimuli.", "the inflammatory cytokine", "inflammatory cytokine tumor", "cytokine tumor necrosis", "tumor necrosis factor", "necrosis factor alpha", "alpha tnf", "\u03b1 is", "is expressed in", "expressed in immune", "in immune and", "immune and nonimmune", "and nonimmune cell", "nonimmune cell types", "cell types including", "types including macrophages", "macrophages t", "cells mast", "cells granulocytes", "granulocytes natural", "killer nk", "nk cells", "cells fibroblasts", "fibroblasts neurons", "neurons keratinocytes", "keratinocytes and smooth", "and smooth muscle", "smooth muscle cells", "muscle cells as", "cells as a", "as a response", "a response to", "response to tissue", "to tissue injury", "tissue injury or", "injury or upon", "or upon immune", "upon immune responses", "immune responses to", "responses to pathogenic", "to pathogenic stimuli", "stimuli k\u00f6ck", "k\u00f6ck a. et", "a. et al.", "et al. 1990", "1990 dubravec", "dubravec db et", "db et al.", "1990 walsh", "walsh lj et", "lj et al.", "et al. 1991", "1991 te", "te velde aa", "velde aa et", "aa et al.", "1990 imaizumi", "imaizumi t et", "t et al.", "et al. 2000", "al. 2000 .", "2000 . tnf", ". tnf \u03b1", "tnf \u03b1 interacts", "\u03b1 interacts with", "interacts with two", "with two receptors", "receptors namely", "namely tnf receptor", "tnf receptor 1", "1 tnfr1", "tnfr1 and", "and tnf receptor", "tnf receptor 2", "2 tnfr2", "tnfr2 . activation", ". activation of", "activation of tnfr1", "of tnfr1 can", "tnfr1 can trigger", "can trigger multiple", "trigger multiple signal", "multiple signal transduction", "signal transduction pathways", "transduction pathways inducing", "pathways inducing inflammation", "inflammation proliferation", "proliferation survival", "survival or cell", "or cell death", "death ward", "ward c et", "c et al.", "et al. 1999", "1999 micheau", "micheau o and", "o and tschopp", "and tschopp j", "tschopp j 2003", "2003 widera", "widera d et", "d et al.", "et al. 2006", "al. 2006 .", "2006 . whether", ". whether a", "whether a tnf", "a tnf \u03b1", "tnf \u03b1 stimulated", "\u03b1 stimulated cell", "stimulated cell will", "cell will survive", "will survive or", "survive or die", "or die is", "die is dependent", "is dependent on", "dependent on autocrine/paracrine", "on autocrine/paracrine signals", "signals and", "and on the", "on the cellular", "the cellular context.

              tnf", "cellular context.

              tnf binding", "context.

              tnf binding to", "binding to tnfr1", "to tnfr1 results", "tnfr1 results initially", "results initially in", "initially in the", "in the formation", "the formation of", "formation of complex", "of complex i", "complex i that", "i that consists", "that consists of", "consists of tnfr1", "tnfr1 tradd", "tradd tnfr1", "tnfr1 associated death", "associated death domain", "traf2 tnf", "tnf receptor associated", "receptor associated factor", "associated factor 2", "ripk1 receptor", "receptor interacting serin/threonine", "interacting serin/threonine protein", "serin/threonine protein kinase", "protein kinase 1", "and e3 ubiquitin", "e3 ubiquitin ligases", "ubiquitin ligases birc2", "ligases birc2 birc3", "birc3 ciap1/2", "ciap1/2 cellular inhibitor", "cellular inhibitor of", "inhibitor of apoptosis", "apoptosis and", "lubac micheau", "j 2003 .", "2003 . the", ". the conjugation", "the conjugation of", "conjugation of ubiquitin", "of ubiquitin chains", "ubiquitin chains by", "chains by birc2/3", "by birc2/3 and", "birc2/3 and lubac", "lubac composed", "composed of hoip", "hoip hoil", "hoil 1 and", "1 and sharpin", "to ripk1 allows", "ripk1 allows further", "allows further recruitment", "further recruitment and", "recruitment and activation", "and activation of", "activation of the", "of the tak1", "tak1 also", "also known as", "known as mitogen", "as mitogen activated", "mitogen activated protein", "activated protein kinase", "protein kinase kinase", "kinase kinase kinase", "kinase kinase 7", "7 map3k7", "complex and i\u03bab", "and i\u03bab kinase", "kinase ikk", "ikk complex.", "complex. tak1 and", "tak1 and ikk", "and ikk phosphorylate", "ikk phosphorylate ripk1", "phosphorylate ripk1 to", "ripk1 to limit", "to limit its", "limit its cytotoxic", "its cytotoxic activity", "activity and", "and activate both", "activate both nuclear", "both nuclear factor", "nuclear factor kappa\u2010light\u2010chain\u2010enhancer", "factor kappa\u2010light\u2010chain\u2010enhancer of", "kappa\u2010light\u2010chain\u2010enhancer of activated", "of activated b", "activated b cells", "cells nfkappab", "nfkappab and", "and mitogen\u2010activated protein", "protein map", "map kinase", "kinase signaling pathways", "signaling pathways promoting", "pathways promoting cell", "promoting cell survival", "cell survival by", "survival by induction", "by induction of", "induction of anti", "of anti apoptotic", "anti apoptotic proteins", "apoptotic proteins such", "proteins such as", "such as birc", "birc cellular", "flice fadd", "fadd like il", "like il 1\u03b2", "il 1\u03b2 converting", "1\u03b2 converting enzyme", "enzyme like", "like inhibitory protein", "protein cflip", "cflip and", "and secretion of", "secretion of pro", "of pro inflammatory", "pro inflammatory cytokines", "cytokines tnf", "tnf and il", "and il 6", "il 6 .", "6 . when", ". when the", "when the survival", "the survival pathway", "survival pathway is", "pathway is inhibited", "inhibited the", "the tradd:traf2:ripk1 detaches", "tradd:traf2:ripk1 detaches from", "detaches from the", "from the membrane", "the membrane bound", "membrane bound tnfr1", "bound tnfr1 signaling", "tnfr1 signaling complex", "signaling complex and", "complex and recruits", "and recruits fas", "recruits fas associated", "fas associated death", "death domain containing", "domain containing protein", "protein fadd", "fadd and", "and procaspase 8", "8 also", "known as complex", "as complex ii", "complex ii .", "ii . once", ". once recruited", "once recruited to", "recruited to fadd", "fadd multiple", "multiple procaspase 8", "procaspase 8 molecules", "8 molecules interact", "molecules interact via", "interact via their", "via their tandem", "their tandem death", "tandem death effector", "death effector domains", "domains ded", "thereby facilitating both", "facilitating both proximity", "both proximity induced", "proximity induced dimerization", "induced dimerization and", "dimerization and proteolytic", "and proteolytic cleavage", "proteolytic cleavage of", "cleavage of procaspase", "of procaspase 8", "8 which", "which are required", "are required for", "required for initiation", "for initiation of", "initiation of apoptotic", "of apoptotic cell", "apoptotic cell death", "death hughes", "hughes ma et", "ma et al.", "et al. 2009", "2009 oberst", "oberst a et", "a et al.", "et al. 2010", "al. 2010 .", "2010 . when", ". when caspase", "when caspase activity", "caspase activity is", "activity is inhibited", "is inhibited under", "inhibited under certain", "under certain pathophysiological", "certain pathophysiological conditions", "conditions e.g.", "e.g. expression", "expression of caspase", "of caspase 8", "caspase 8 inhibitory", "8 inhibitory proteins", "inhibitory proteins such", "such as crma", "as crma and", "crma and vica", "and vica after", "vica after infection", "after infection with", "infection with cowpox", "with cowpox virus", "cowpox virus or", "virus or cmv", "cmv or", "or by pharmacological", "by pharmacological agents", "agents deubiquitinated", "deubiquitinated ripk1 is", "ripk1 is physically", "is physically and", "physically and functionally", "and functionally engaged", "functionally engaged by", "engaged by its", "by its homolog", "its homolog ripk3", "homolog ripk3 leading", "ripk3 leading to", "leading to formation", "to formation of", "formation of the", "of the necrosome", "necrosome a", "a necroptosis inducing", "necroptosis inducing complex", "inducing complex consisting", "complex consisting of", "consisting of ripk1", "of ripk1 and", "ripk1 and ripk3", "ripk3 tewari", "tewari m &", "m & dixit", "& dixit vm", "dixit vm 1995", "1995 fliss", "fliss pm &", "pm & brune", "& brune w", "brune w 2012", "2012 sawai", "sawai h 2013", "2013 moquin", "moquin dm et", "dm et al.", "et al. 2013", "2013 kalai", "kalai m et", "m et al.", "et al. 2002", "2002 cho", "cho ys et", "ys et al.", "2009 he", "he s et", "s et al.", "2009 zhang", "zhang dw et", "dw et al.", "2009 . within", ". within the", "within the complex", "the complex ii", "complex ii procaspase", "ii procaspase 8", "procaspase 8 can", "8 can also", "can also form", "also form heterodimers", "form heterodimers with", "heterodimers with cflip", "with cflip isoforms", "isoforms flip", "long l", "l and", "and flip short", "short s", "which are encoded", "are encoded by", "encoded by the", "by the nfkappab", "the nfkappab target", "nfkappab target gene", "target gene cflar", "cflar irmler", "irmler m et", "et al. 1997", "1997 boatright", "boatright km et", "km et al.", "et al. 2004", "2004 yu", "yu jw et", "jw et al.", "2009 pop", "pop c et", "et al. 2011", "al. 2011 .", "2011 . flip", ". flip s", "s appears", "appears to act", "to act purely", "act purely as", "purely as an", "as an antagonist", "an antagonist of", "antagonist of caspase", "caspase 8 activity", "8 activity blocking", "activity blocking apoptotic", "blocking apoptotic but", "apoptotic but promoting", "but promoting necroptotic", "promoting necroptotic cell", "necroptotic cell death", "death feoktistova", "feoktistova et", "2011 . the", ". the regulatory", "the regulatory function", "regulatory function of", "function of flip", "of flip l", "l has", "has been found", "been found to", "found to differ", "to differ depending", "differ depending on", "depending on its", "on its expression", "its expression levels.", "expression levels. flip", "levels. flip l", "l was", "was shown to", "shown to inhibit", "to inhibit death", "inhibit death receptor", "receptor dr", "dr mediated", "mediated apoptosis only", "apoptosis only when", "only when expressed", "when expressed at", "expressed at high", "at high levels", "levels while", "while low cell", "low cell levels", "cell levels of", "levels of flip", "l enhanced", "enhanced dr signaling", "dr signaling to", "signaling to apoptosis", "apoptosis boatright", "2004 okano", "okano h et", "h et al.", "et al. 2003", "2003 yerbes", "yerbes r et", "r et al.", "2011 yu", "2009 hughes", "et al. 2016", "al. 2016 .", "2016 . in", ". in addition", "addition caspase", "caspase 8:flip l", "l heterodimer", "heterodimer activity within", "activity within the", "within the tradd:traf2:ripk1:fadd:casp8:flip", "the tradd:traf2:ripk1:fadd:casp8:flip l", "l complex", "complex allowed cleavage", "allowed cleavage of", "cleavage of ripk1", "of ripk1 to", "ripk1 to cause", "to cause the", "cause the dissociation", "the dissociation of", "dissociation of the", "of the tradd:traf2:rip1:fadd:casp8", "tradd:traf2:rip1:fadd:casp8 thereby", "thereby inhibiting ripk1", "inhibiting ripk1 mediated", "ripk1 mediated necroptosis", "necroptosis feoktistova", "2011 2012", "2012 . tnf", "tnf \u03b1 can", "\u03b1 can also", "can also activate", "also activate sphingomyelinase", "sphingomyelinase smase", "smase such", "such as smpd2", "as smpd2 3", "3 proteins", "proteins to catalyze", "to catalyze hydrolysis", "catalyze hydrolysis of", "hydrolysis of sphingomyeline", "of sphingomyeline into", "sphingomyeline into ceramide", "ceramide adam", "adam d et", "d et al.1996", "al.1996 adam", "adam klages s", "klages s et", "et al. 1998", "1998 s\u00e9gui", "s\u00e9gui b et", "b et al.", "et al. 2001", "al. 2001 .", "2001 . activation", "activation of neutral", "of neutral smpd2", "neutral smpd2 3", "smpd2 3 leads", "3 leads to", "leads to an", "to an accumulation", "an accumulation of", "accumulation of ceramide", "of ceramide at", "ceramide at the", "at the cell", "the cell surface", "cell surface and", "surface and has", "and has proinflammatory", "has proinflammatory effects.", "proinflammatory effects. however", "however tnf", "tnf can also", "also activate the", "activate the pro", "the pro apoptotic", "pro apoptotic acidic", "apoptotic acidic smase", "acidic smase via", "smase via caspase", "via caspase 8", "caspase 8 mediated", "8 mediated activation", "mediated activation of", "activation of caspase", "of caspase 7", "caspase 7 which", "7 which in", "which in turn", "in turn proteolytically", "turn proteolytically cleaves", "proteolytically cleaves and", "cleaves and activates", "and activates the", "activates the 72kda", "the 72kda pro", "72kda pro a", "pro a smase", "a smase form", "form edelmann", "edelmann b et", "2011 . ceramide", ". ceramide induces", "ceramide induces anti", "induces anti proliferative", "anti proliferative and", "proliferative and pro", "and pro apoptotic", "pro apoptotic responses.", "apoptotic responses. further", "further ceramide", "ceramide can be", "can be converted", "be converted by", "converted by ceramidase", "by ceramidase into", "ceramidase into sphingosine", "sphingosine which", "in turn is", "turn is phosphorylated", "is phosphorylated by", "phosphorylated by sphingosine", "by sphingosine kinase", "sphingosine kinase into", "kinase into sphingosine", "into sphingosine 1", "sphingosine 1 phosphate", "phosphate s1p", "s1p . s1p", ". s1p exerts", "s1p exerts the", "exerts the opposite", "the opposite biological", "opposite biological effects", "biological effects to", "effects to ceramide", "to ceramide by", "ceramide by activating", "by activating cytoprotective", "activating cytoprotective signaling", "cytoprotective signaling to", "signaling to promote", "to promote cell", "promote cell growth", "cell growth counteracting", "growth counteracting the", "counteracting the apoptotic", "the apoptotic stimuli", "stimuli cuvillier", "cuvillier o et", "o et al.", "et al. 1996", "al. 1996 .", "1996 . thus", "thus tnf", "tnf \u03b1 induced", "\u03b1 induced tnfr1", "induced tnfr1 activation", "tnfr1 activation leads", "activation leads to", "leads to divergent", "to divergent intracellular", "divergent intracellular signaling", "intracellular signaling networks", "signaling networks with", "networks with extensive", "with extensive cross", "extensive cross talk", "cross talk between", "talk between the", "between the pro", "the pro apoptotic/necroptotic", "pro apoptotic/necroptotic pathway", "pathway and", "and the other", "the other nfkappab", "and mapk pathways", "mapk pathways providing", "pathways providing highly", "providing highly specific", "highly specific cell", "specific cell responses", "cell responses initiated", "responses initiated by", "initiated by various", "by various types", "various types of", "types of stimuli.", "the inflammatory cytokine tumor", "inflammatory cytokine tumor necrosis", "cytokine tumor necrosis factor", "tumor necrosis factor alpha", "factor alpha tnf", "alpha tnf \u03b1", "tnf \u03b1 is", "\u03b1 is expressed", "is expressed in immune", "expressed in immune and", "in immune and nonimmune", "immune and nonimmune cell", "and nonimmune cell types", "nonimmune cell types including", "cell types including macrophages", "including macrophages t", "macrophages t cells", "t cells mast", "cells mast cells", "mast cells granulocytes", "granulocytes natural killer", "natural killer nk", "neurons keratinocytes and", "keratinocytes and smooth muscle", "and smooth muscle cells", "smooth muscle cells as", "muscle cells as a", "cells as a response", "as a response to", "a response to tissue", "response to tissue injury", "to tissue injury or", "tissue injury or upon", "injury or upon immune", "or upon immune responses", "upon immune responses to", "immune responses to pathogenic", "responses to pathogenic stimuli", "pathogenic stimuli k\u00f6ck", "stimuli k\u00f6ck a.", "k\u00f6ck a. et al.", "a. et al. 1990", "al. 1990 dubravec", "1990 dubravec db", "dubravec db et al.", "db et al. 1990", "al. 1990 walsh", "1990 walsh lj", "walsh lj et al.", "lj et al. 1991", "al. 1991 te", "1991 te velde", "te velde aa et", "velde aa et al.", "aa et al. 1990", "al. 1990 imaizumi", "1990 imaizumi t", "imaizumi t et al.", "t et al. 2000", "et al. 2000 .", "al. 2000 . tnf", "2000 . tnf \u03b1", ". tnf \u03b1 interacts", "tnf \u03b1 interacts with", "\u03b1 interacts with two", "interacts with two receptors", "two receptors namely", "receptors namely tnf", "namely tnf receptor 1", "receptor 1 tnfr1", "tnfr1 and tnf", "and tnf receptor 2", "receptor 2 tnfr2", "2 tnfr2 .", "tnfr2 . activation of", ". activation of tnfr1", "activation of tnfr1 can", "of tnfr1 can trigger", "tnfr1 can trigger multiple", "can trigger multiple signal", "trigger multiple signal transduction", "multiple signal transduction pathways", "signal transduction pathways inducing", "transduction pathways inducing inflammation", "inducing inflammation proliferation", "proliferation survival or", "survival or cell death", "cell death ward", "death ward c", "ward c et al.", "c et al. 1999", "al. 1999 micheau", "1999 micheau o", "micheau o and tschopp", "o and tschopp j", "and tschopp j 2003", "j 2003 widera", "2003 widera d", "widera d et al.", "d et al. 2006", "et al. 2006 .", "al. 2006 . whether", "2006 . whether a", ". whether a tnf", "whether a tnf \u03b1", "a tnf \u03b1 stimulated", "tnf \u03b1 stimulated cell", "\u03b1 stimulated cell will", "stimulated cell will survive", "cell will survive or", "will survive or die", "survive or die is", "or die is dependent", "die is dependent on", "is dependent on autocrine/paracrine", "dependent on autocrine/paracrine signals", "autocrine/paracrine signals and", "signals and on", "and on the cellular", "on the cellular context.

              tnf", "the cellular context.

              tnf binding", "cellular context.

              tnf binding to", "context.

              tnf binding to tnfr1", "binding to tnfr1 results", "to tnfr1 results initially", "tnfr1 results initially in", "results initially in the", "initially in the formation", "in the formation of", "the formation of complex", "formation of complex i", "of complex i that", "complex i that consists", "i that consists of", "that consists of tnfr1", "of tnfr1 tradd", "tradd tnfr1 associated", "tnfr1 associated death domain", "domain traf2", "traf2 tnf receptor", "tnf receptor associated factor", "receptor associated factor 2", "2 ripk1", "ripk1 receptor interacting", "receptor interacting serin/threonine protein", "interacting serin/threonine protein kinase", "serin/threonine protein kinase 1", "and e3 ubiquitin ligases", "e3 ubiquitin ligases birc2", "ubiquitin ligases birc2 birc3", "birc2 birc3 ciap1/2", "birc3 ciap1/2 cellular", "ciap1/2 cellular inhibitor of", "cellular inhibitor of apoptosis", "of apoptosis and", "apoptosis and lubac", "and lubac micheau", "lubac micheau o", "tschopp j 2003 .", "j 2003 . the", "2003 . the conjugation", ". the conjugation of", "the conjugation of ubiquitin", "conjugation of ubiquitin chains", "of ubiquitin chains by", "ubiquitin chains by birc2/3", "chains by birc2/3 and", "by birc2/3 and lubac", "and lubac composed", "lubac composed of", "of hoip hoil", "hoip hoil 1", "hoil 1 and sharpin", "sharpin to", "to ripk1 allows further", "ripk1 allows further recruitment", "allows further recruitment and", "further recruitment and activation", "recruitment and activation of", "and activation of the", "activation of the tak1", "the tak1 also", "tak1 also known", "also known as mitogen", "known as mitogen activated", "as mitogen activated protein", "mitogen activated protein kinase", "activated protein kinase kinase", "protein kinase kinase kinase", "kinase kinase kinase 7", "kinase 7 map3k7", "map3k7 complex", "complex and i\u03bab kinase", "i\u03bab kinase ikk", "ikk complex. tak1", "complex. tak1 and ikk", "tak1 and ikk phosphorylate", "and ikk phosphorylate ripk1", "ikk phosphorylate ripk1 to", "phosphorylate ripk1 to limit", "ripk1 to limit its", "to limit its cytotoxic", "limit its cytotoxic activity", "cytotoxic activity and", "activity and activate", "and activate both nuclear", "activate both nuclear factor", "both nuclear factor kappa\u2010light\u2010chain\u2010enhancer", "nuclear factor kappa\u2010light\u2010chain\u2010enhancer of", "factor kappa\u2010light\u2010chain\u2010enhancer of activated", "kappa\u2010light\u2010chain\u2010enhancer of activated b", "of activated b cells", "b cells nfkappab", "nfkappab and mitogen\u2010activated", "mitogen\u2010activated protein map", "map kinase signaling", "kinase signaling pathways promoting", "signaling pathways promoting cell", "pathways promoting cell survival", "promoting cell survival by", "cell survival by induction", "survival by induction of", "by induction of anti", "induction of anti apoptotic", "of anti apoptotic proteins", "anti apoptotic proteins such", "apoptotic proteins such as", "proteins such as birc", "as birc cellular", "birc cellular flice", "cellular flice fadd", "flice fadd like", "fadd like il 1\u03b2", "like il 1\u03b2 converting", "il 1\u03b2 converting enzyme", "converting enzyme like", "enzyme like inhibitory", "inhibitory protein cflip", "cflip and secretion", "and secretion of pro", "secretion of pro inflammatory", "of pro inflammatory cytokines", "inflammatory cytokines tnf", "cytokines tnf and", "tnf and il 6", "and il 6 .", "il 6 . when", "6 . when the", ". when the survival", "when the survival pathway", "the survival pathway is", "survival pathway is inhibited", "is inhibited the", "inhibited the tradd:traf2:ripk1", "the tradd:traf2:ripk1 detaches from", "tradd:traf2:ripk1 detaches from the", "detaches from the membrane", "from the membrane bound", "the membrane bound tnfr1", "membrane bound tnfr1 signaling", "bound tnfr1 signaling complex", "tnfr1 signaling complex and", "signaling complex and recruits", "complex and recruits fas", "and recruits fas associated", "recruits fas associated death", "fas associated death domain", "associated death domain containing", "death domain containing protein", "containing protein fadd", "fadd and procaspase", "procaspase 8 also", "8 also known", "also known as complex", "known as complex ii", "as complex ii .", "complex ii . once", "ii . once recruited", ". once recruited to", "once recruited to fadd", "to fadd multiple", "fadd multiple procaspase", "multiple procaspase 8 molecules", "procaspase 8 molecules interact", "8 molecules interact via", "molecules interact via their", "interact via their tandem", "via their tandem death", "their tandem death effector", "tandem death effector domains", "effector domains ded", "ded thereby", "thereby facilitating both proximity", "facilitating both proximity induced", "both proximity induced dimerization", "proximity induced dimerization and", "induced dimerization and proteolytic", "dimerization and proteolytic cleavage", "and proteolytic cleavage of", "proteolytic cleavage of procaspase", "cleavage of procaspase 8", "procaspase 8 which", "8 which are", "which are required for", "are required for initiation", "required for initiation of", "for initiation of apoptotic", "initiation of apoptotic cell", "of apoptotic cell death", "cell death hughes", "death hughes ma", "hughes ma et al.", "ma et al. 2009", "al. 2009 oberst", "2009 oberst a", "oberst a et al.", "a et al. 2010", "et al. 2010 .", "al. 2010 . when", "2010 . when caspase", ". when caspase activity", "when caspase activity is", "caspase activity is inhibited", "activity is inhibited under", "is inhibited under certain", "inhibited under certain pathophysiological", "under certain pathophysiological conditions", "pathophysiological conditions e.g.", "e.g. expression of", "expression of caspase 8", "of caspase 8 inhibitory", "caspase 8 inhibitory proteins", "8 inhibitory proteins such", "inhibitory proteins such as", "proteins such as crma", "such as crma and", "as crma and vica", "crma and vica after", "and vica after infection", "vica after infection with", "after infection with cowpox", "infection with cowpox virus", "with cowpox virus or", "cowpox virus or cmv", "or cmv or", "cmv or by", "or by pharmacological agents", "pharmacological agents deubiquitinated", "agents deubiquitinated ripk1", "deubiquitinated ripk1 is physically", "ripk1 is physically and", "is physically and functionally", "physically and functionally engaged", "and functionally engaged by", "functionally engaged by its", "engaged by its homolog", "by its homolog ripk3", "its homolog ripk3 leading", "homolog ripk3 leading to", "ripk3 leading to formation", "leading to formation of", "to formation of the", "formation of the necrosome", "the necrosome a", "necrosome a necroptosis", "a necroptosis inducing complex", "necroptosis inducing complex consisting", "inducing complex consisting of", "complex consisting of ripk1", "consisting of ripk1 and", "of ripk1 and ripk3", "and ripk3 tewari", "ripk3 tewari m", "tewari m & dixit", "m & dixit vm", "& dixit vm 1995", "vm 1995 fliss", "1995 fliss pm", "fliss pm & brune", "pm & brune w", "& brune w 2012", "w 2012 sawai", "2012 sawai h", "h 2013 moquin", "2013 moquin dm", "moquin dm et al.", "dm et al. 2013", "al. 2013 kalai", "2013 kalai m", "kalai m et al.", "m et al. 2002", "al. 2002 cho", "2002 cho ys", "cho ys et al.", "ys et al. 2009", "al. 2009 he", "2009 he s", "he s et al.", "s et al. 2009", "al. 2009 zhang", "2009 zhang dw", "zhang dw et al.", "al. 2009 .", "2009 . within the", ". within the complex", "within the complex ii", "the complex ii procaspase", "complex ii procaspase 8", "ii procaspase 8 can", "procaspase 8 can also", "8 can also form", "can also form heterodimers", "also form heterodimers with", "form heterodimers with cflip", "heterodimers with cflip isoforms", "cflip isoforms flip", "isoforms flip long", "flip long l", "l and flip", "flip short s", "s which", "which are encoded by", "are encoded by the", "encoded by the nfkappab", "by the nfkappab target", "the nfkappab target gene", "nfkappab target gene cflar", "gene cflar irmler", "cflar irmler m", "irmler m et al.", "m et al. 1997", "al. 1997 boatright", "1997 boatright km", "boatright km et al.", "km et al. 2004", "al. 2004 yu", "2004 yu jw", "yu jw et al.", "jw et al. 2009", "al. 2009 pop", "2009 pop c", "pop c et al.", "c et al. 2011", "et al. 2011 .", "al. 2011 . flip", "2011 . flip s", "flip s appears", "s appears to", "appears to act purely", "to act purely as", "act purely as an", "purely as an antagonist", "as an antagonist of", "an antagonist of caspase", "antagonist of caspase 8", "of caspase 8 activity", "caspase 8 activity blocking", "8 activity blocking apoptotic", "activity blocking apoptotic but", "blocking apoptotic but promoting", "apoptotic but promoting necroptotic", "but promoting necroptotic cell", "promoting necroptotic cell death", "cell death feoktistova", "feoktistova et al.", "al. 2011 . the", "2011 . the regulatory", ". the regulatory function", "the regulatory function of", "regulatory function of flip", "function of flip l", "flip l has", "l has been", "has been found to", "been found to differ", "found to differ depending", "to differ depending on", "differ depending on its", "depending on its expression", "on its expression levels.", "its expression levels. flip", "expression levels. flip l", "flip l was", "l was shown", "was shown to inhibit", "shown to inhibit death", "to inhibit death receptor", "death receptor dr", "dr mediated apoptosis", "mediated apoptosis only when", "apoptosis only when expressed", "only when expressed at", "when expressed at high", "expressed at high levels", "high levels while", "levels while low", "while low cell levels", "low cell levels of", "cell levels of flip", "levels of flip l", "flip l enhanced", "l enhanced dr", "enhanced dr signaling to", "dr signaling to apoptosis", "to apoptosis boatright", "apoptosis boatright km", "al. 2004 okano", "2004 okano h", "okano h et al.", "h et al. 2003", "al. 2003 yerbes", "2003 yerbes r", "yerbes r et al.", "r et al. 2011", "al. 2011 yu", "2011 yu jw", "al. 2009 hughes", "2009 hughes ma", "ma et al. 2016", "et al. 2016 .", "al. 2016 . in", "2016 . in addition", "in addition caspase", "addition caspase 8:flip", "8:flip l heterodimer", "l heterodimer activity", "heterodimer activity within the", "activity within the tradd:traf2:ripk1:fadd:casp8:flip", "within the tradd:traf2:ripk1:fadd:casp8:flip l", "tradd:traf2:ripk1:fadd:casp8:flip l complex", "l complex allowed", "complex allowed cleavage of", "allowed cleavage of ripk1", "cleavage of ripk1 to", "of ripk1 to cause", "ripk1 to cause the", "to cause the dissociation", "cause the dissociation of", "the dissociation of the", "dissociation of the tradd:traf2:rip1:fadd:casp8", "the tradd:traf2:rip1:fadd:casp8 thereby", "tradd:traf2:rip1:fadd:casp8 thereby inhibiting", "thereby inhibiting ripk1 mediated", "inhibiting ripk1 mediated necroptosis", "mediated necroptosis feoktistova", "al. 2011 2012", "2011 2012 .", "2012 . tnf \u03b1", ". tnf \u03b1 can", "tnf \u03b1 can also", "\u03b1 can also activate", "can also activate sphingomyelinase", "activate sphingomyelinase smase", "smase such as", "such as smpd2 3", "smpd2 3 proteins", "3 proteins to", "proteins to catalyze hydrolysis", "to catalyze hydrolysis of", "catalyze hydrolysis of sphingomyeline", "hydrolysis of sphingomyeline into", "of sphingomyeline into ceramide", "into ceramide adam", "ceramide adam d", "adam d et al.1996", "et al.1996 adam", "al.1996 adam klages", "adam klages s et", "klages s et al.", "s et al. 1998", "al. 1998 s\u00e9gui", "1998 s\u00e9gui b", "s\u00e9gui b et al.", "b et al. 2001", "et al. 2001 .", "al. 2001 . activation", "2001 . activation of", ". activation of neutral", "activation of neutral smpd2", "of neutral smpd2 3", "neutral smpd2 3 leads", "smpd2 3 leads to", "3 leads to an", "leads to an accumulation", "to an accumulation of", "an accumulation of ceramide", "accumulation of ceramide at", "of ceramide at the", "ceramide at the cell", "at the cell surface", "the cell surface and", "cell surface and has", "surface and has proinflammatory", "and has proinflammatory effects.", "has proinflammatory effects. however", "effects. however tnf", "however tnf can", "tnf can also activate", "can also activate the", "also activate the pro", "activate the pro apoptotic", "the pro apoptotic acidic", "pro apoptotic acidic smase", "apoptotic acidic smase via", "acidic smase via caspase", "smase via caspase 8", "via caspase 8 mediated", "caspase 8 mediated activation", "8 mediated activation of", "mediated activation of caspase", "activation of caspase 7", "of caspase 7 which", "caspase 7 which in", "7 which in turn", "which in turn proteolytically", "in turn proteolytically cleaves", "turn proteolytically cleaves and", "proteolytically cleaves and activates", "cleaves and activates the", "and activates the 72kda", "activates the 72kda pro", "the 72kda pro a", "72kda pro a smase", "pro a smase form", "smase form edelmann", "form edelmann b", "edelmann b et al.", "b et al. 2011", "al. 2011 . ceramide", "2011 . ceramide induces", ". ceramide induces anti", "ceramide induces anti proliferative", "induces anti proliferative and", "anti proliferative and pro", "proliferative and pro apoptotic", "and pro apoptotic responses.", "pro apoptotic responses. further", "responses. further ceramide", "further ceramide can", "ceramide can be converted", "can be converted by", "be converted by ceramidase", "converted by ceramidase into", "by ceramidase into sphingosine", "into sphingosine which", "sphingosine which in", "which in turn is", "in turn is phosphorylated", "turn is phosphorylated by", "is phosphorylated by sphingosine", "phosphorylated by sphingosine kinase", "by sphingosine kinase into", "sphingosine kinase into sphingosine", "kinase into sphingosine 1", "into sphingosine 1 phosphate", "1 phosphate s1p", "phosphate s1p .", "s1p . s1p exerts", ". s1p exerts the", "s1p exerts the opposite", "exerts the opposite biological", "the opposite biological effects", "opposite biological effects to", "biological effects to ceramide", "effects to ceramide by", "to ceramide by activating", "ceramide by activating cytoprotective", "by activating cytoprotective signaling", "activating cytoprotective signaling to", "cytoprotective signaling to promote", "signaling to promote cell", "to promote cell growth", "promote cell growth counteracting", "cell growth counteracting the", "growth counteracting the apoptotic", "counteracting the apoptotic stimuli", "apoptotic stimuli cuvillier", "stimuli cuvillier o", "cuvillier o et al.", "o et al. 1996", "et al. 1996 .", "al. 1996 . thus", ". thus tnf", "thus tnf \u03b1", "tnf \u03b1 induced tnfr1", "\u03b1 induced tnfr1 activation", "induced tnfr1 activation leads", "tnfr1 activation leads to", "activation leads to divergent", "leads to divergent intracellular", "to divergent intracellular signaling", "divergent intracellular signaling networks", "intracellular signaling networks with", "signaling networks with extensive", "networks with extensive cross", "with extensive cross talk", "extensive cross talk between", "cross talk between the", "talk between the pro", "between the pro apoptotic/necroptotic", "the pro apoptotic/necroptotic pathway", "apoptotic/necroptotic pathway and", "pathway and the", "and the other nfkappab", "other nfkappab and", "nfkappab and mapk", "and mapk pathways providing", "mapk pathways providing highly", "pathways providing highly specific", "providing highly specific cell", "highly specific cell responses", "specific cell responses initiated", "cell responses initiated by", "responses initiated by various", "initiated by various types", "by various types of", "various types of stimuli.", "the inflammatory cytokine tumor necrosis", "inflammatory cytokine tumor necrosis factor", "cytokine tumor necrosis factor alpha", "necrosis factor alpha tnf", "factor alpha tnf \u03b1", "tnf \u03b1 is expressed", "\u03b1 is expressed in", "is expressed in immune and", "expressed in immune and nonimmune", "in immune and nonimmune cell", "immune and nonimmune cell types", "and nonimmune cell types including", "nonimmune cell types including macrophages", "types including macrophages t", "including macrophages t cells", "t cells mast cells", "cells granulocytes natural", "killer nk cells", "nk cells fibroblasts", "cells fibroblasts neurons", "fibroblasts neurons keratinocytes", "neurons keratinocytes and smooth", "keratinocytes and smooth muscle cells", "and smooth muscle cells as", "smooth muscle cells as a", "muscle cells as a response", "cells as a response to", "as a response to tissue", "a response to tissue injury", "response to tissue injury or", "to tissue injury or upon", "tissue injury or upon immune", "injury or upon immune responses", "or upon immune responses to", "upon immune responses to pathogenic", "immune responses to pathogenic stimuli", "to pathogenic stimuli k\u00f6ck", "pathogenic stimuli k\u00f6ck a.", "stimuli k\u00f6ck a. et", "k\u00f6ck a. et al. 1990", "et al. 1990 dubravec", "al. 1990 dubravec db", "1990 dubravec db et", "dubravec db et al. 1990", "et al. 1990 walsh", "al. 1990 walsh lj", "1990 walsh lj et", "walsh lj et al. 1991", "et al. 1991 te", "al. 1991 te velde", "1991 te velde aa", "te velde aa et al.", "velde aa et al. 1990", "et al. 1990 imaizumi", "al. 1990 imaizumi t", "1990 imaizumi t et", "imaizumi t et al. 2000", "t et al. 2000 .", "et al. 2000 . tnf", "al. 2000 . tnf \u03b1", "2000 . tnf \u03b1 interacts", ". tnf \u03b1 interacts with", "tnf \u03b1 interacts with two", "\u03b1 interacts with two receptors", "with two receptors namely", "two receptors namely tnf", "receptors namely tnf receptor", "tnf receptor 1 tnfr1", "1 tnfr1 and", "tnfr1 and tnf receptor", "tnf receptor 2 tnfr2", "receptor 2 tnfr2 .", "2 tnfr2 . activation", "tnfr2 . activation of tnfr1", ". activation of tnfr1 can", "activation of tnfr1 can trigger", "of tnfr1 can trigger multiple", "tnfr1 can trigger multiple signal", "can trigger multiple signal transduction", "trigger multiple signal transduction pathways", "multiple signal transduction pathways inducing", "signal transduction pathways inducing inflammation", "pathways inducing inflammation proliferation", "inflammation proliferation survival", "proliferation survival or cell", "or cell death ward", "cell death ward c", "death ward c et", "ward c et al. 1999", "et al. 1999 micheau", "al. 1999 micheau o", "1999 micheau o and", "micheau o and tschopp j", "o and tschopp j 2003", "tschopp j 2003 widera", "j 2003 widera d", "2003 widera d et", "widera d et al. 2006", "d et al. 2006 .", "et al. 2006 . whether", "al. 2006 . whether a", "2006 . whether a tnf", ". whether a tnf \u03b1", "whether a tnf \u03b1 stimulated", "a tnf \u03b1 stimulated cell", "tnf \u03b1 stimulated cell will", "\u03b1 stimulated cell will survive", "stimulated cell will survive or", "cell will survive or die", "will survive or die is", "survive or die is dependent", "or die is dependent on", "die is dependent on autocrine/paracrine", "is dependent on autocrine/paracrine signals", "on autocrine/paracrine signals and", "autocrine/paracrine signals and on", "signals and on the", "and on the cellular context.

              tnf", "on the cellular context.

              tnf binding", "the cellular context.

              tnf binding to", "cellular context.

              tnf binding to tnfr1", "context.

              tnf binding to tnfr1 results", "binding to tnfr1 results initially", "to tnfr1 results initially in", "tnfr1 results initially in the", "results initially in the formation", "initially in the formation of", "in the formation of complex", "the formation of complex i", "formation of complex i that", "of complex i that consists", "complex i that consists of", "i that consists of tnfr1", "consists of tnfr1 tradd", "tnfr1 tradd tnfr1", "tradd tnfr1 associated death", "death domain traf2", "traf2 tnf receptor associated", "tnf receptor associated factor 2", "factor 2 ripk1", "ripk1 receptor interacting serin/threonine", "receptor interacting serin/threonine protein kinase", "interacting serin/threonine protein kinase 1", "kinase 1 and", "1 and e3", "and e3 ubiquitin ligases birc2", "e3 ubiquitin ligases birc2 birc3", "ligases birc2 birc3 ciap1/2", "birc2 birc3 ciap1/2 cellular", "birc3 ciap1/2 cellular inhibitor", "ciap1/2 cellular inhibitor of apoptosis", "inhibitor of apoptosis and", "of apoptosis and lubac", "and lubac micheau o", "lubac micheau o and", "and tschopp j 2003 .", "tschopp j 2003 . the", "j 2003 . the conjugation", "2003 . the conjugation of", ". the conjugation of ubiquitin", "the conjugation of ubiquitin chains", "conjugation of ubiquitin chains by", "of ubiquitin chains by birc2/3", "ubiquitin chains by birc2/3 and", "chains by birc2/3 and lubac", "birc2/3 and lubac composed", "and lubac composed of", "lubac composed of hoip", "composed of hoip hoil", "of hoip hoil 1", "hoip hoil 1 and", "and sharpin to", "sharpin to ripk1", "to ripk1 allows further recruitment", "ripk1 allows further recruitment and", "allows further recruitment and activation", "further recruitment and activation of", "recruitment and activation of the", "and activation of the tak1", "of the tak1 also", "the tak1 also known", "tak1 also known as", "also known as mitogen activated", "known as mitogen activated protein", "as mitogen activated protein kinase", "mitogen activated protein kinase kinase", "activated protein kinase kinase kinase", "protein kinase kinase kinase 7", "kinase kinase 7 map3k7", "map3k7 complex and", "and i\u03bab kinase ikk", "kinase ikk complex.", "ikk complex. tak1 and", "complex. tak1 and ikk phosphorylate", "tak1 and ikk phosphorylate ripk1", "and ikk phosphorylate ripk1 to", "ikk phosphorylate ripk1 to limit", "phosphorylate ripk1 to limit its", "ripk1 to limit its cytotoxic", "to limit its cytotoxic activity", "its cytotoxic activity and", "cytotoxic activity and activate", "activity and activate both", "and activate both nuclear factor", "activate both nuclear factor kappa\u2010light\u2010chain\u2010enhancer", "both nuclear factor kappa\u2010light\u2010chain\u2010enhancer of", "nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated", "factor kappa\u2010light\u2010chain\u2010enhancer of activated b", "kappa\u2010light\u2010chain\u2010enhancer of activated b cells", "activated b cells nfkappab", "cells nfkappab and", "nfkappab and mitogen\u2010activated protein", "and mitogen\u2010activated protein map", "protein map kinase", "map kinase signaling pathways", "kinase signaling pathways promoting cell", "signaling pathways promoting cell survival", "pathways promoting cell survival by", "promoting cell survival by induction", "cell survival by induction of", "survival by induction of anti", "by induction of anti apoptotic", "induction of anti apoptotic proteins", "of anti apoptotic proteins such", "anti apoptotic proteins such as", "apoptotic proteins such as birc", "such as birc cellular", "as birc cellular flice", "cellular flice fadd like", "flice fadd like il", "fadd like il 1\u03b2 converting", "like il 1\u03b2 converting enzyme", "1\u03b2 converting enzyme like", "converting enzyme like inhibitory", "enzyme like inhibitory protein", "like inhibitory protein cflip", "protein cflip and", "cflip and secretion of", "and secretion of pro inflammatory", "secretion of pro inflammatory cytokines", "pro inflammatory cytokines tnf", "inflammatory cytokines tnf and", "cytokines tnf and il", "tnf and il 6 .", "and il 6 . when", "il 6 . when the", "6 . when the survival", ". when the survival pathway", "when the survival pathway is", "the survival pathway is inhibited", "pathway is inhibited the", "is inhibited the tradd:traf2:ripk1", "inhibited the tradd:traf2:ripk1 detaches", "the tradd:traf2:ripk1 detaches from the", "tradd:traf2:ripk1 detaches from the membrane", "detaches from the membrane bound", "from the membrane bound tnfr1", "the membrane bound tnfr1 signaling", "membrane bound tnfr1 signaling complex", "bound tnfr1 signaling complex and", "tnfr1 signaling complex and recruits", "signaling complex and recruits fas", "complex and recruits fas associated", "and recruits fas associated death", "recruits fas associated death domain", "fas associated death domain containing", "associated death domain containing protein", "domain containing protein fadd", "protein fadd and", "fadd and procaspase 8", "and procaspase 8 also", "procaspase 8 also known", "8 also known as", "also known as complex ii", "known as complex ii .", "as complex ii . once", "complex ii . once recruited", "ii . once recruited to", ". once recruited to fadd", "recruited to fadd multiple", "to fadd multiple procaspase", "fadd multiple procaspase 8", "multiple procaspase 8 molecules interact", "procaspase 8 molecules interact via", "8 molecules interact via their", "molecules interact via their tandem", "interact via their tandem death", "via their tandem death effector", "their tandem death effector domains", "death effector domains ded", "ded thereby facilitating", "thereby facilitating both proximity induced", "facilitating both proximity induced dimerization", "both proximity induced dimerization and", "proximity induced dimerization and proteolytic", "induced dimerization and proteolytic cleavage", "dimerization and proteolytic cleavage of", "and proteolytic cleavage of procaspase", "proteolytic cleavage of procaspase 8", "of procaspase 8 which", "procaspase 8 which are", "8 which are required", "which are required for initiation", "are required for initiation of", "required for initiation of apoptotic", "for initiation of apoptotic cell", "initiation of apoptotic cell death", "apoptotic cell death hughes", "cell death hughes ma", "death hughes ma et", "hughes ma et al. 2009", "et al. 2009 oberst", "al. 2009 oberst a", "2009 oberst a et", "oberst a et al. 2010", "a et al. 2010 .", "et al. 2010 . when", "al. 2010 . when caspase", "2010 . when caspase activity", ". when caspase activity is", "when caspase activity is inhibited", "caspase activity is inhibited under", "activity is inhibited under certain", "is inhibited under certain pathophysiological", "inhibited under certain pathophysiological conditions", "certain pathophysiological conditions e.g.", "conditions e.g. expression", "e.g. expression of caspase", "expression of caspase 8 inhibitory", "of caspase 8 inhibitory proteins", "caspase 8 inhibitory proteins such", "8 inhibitory proteins such as", "inhibitory proteins such as crma", "proteins such as crma and", "such as crma and vica", "as crma and vica after", "crma and vica after infection", "and vica after infection with", "vica after infection with cowpox", "after infection with cowpox virus", "infection with cowpox virus or", "with cowpox virus or cmv", "virus or cmv or", "or cmv or by", "cmv or by pharmacological", "by pharmacological agents deubiquitinated", "pharmacological agents deubiquitinated ripk1", "agents deubiquitinated ripk1 is", "deubiquitinated ripk1 is physically and", "ripk1 is physically and functionally", "is physically and functionally engaged", "physically and functionally engaged by", "and functionally engaged by its", "functionally engaged by its homolog", "engaged by its homolog ripk3", "by its homolog ripk3 leading", "its homolog ripk3 leading to", "homolog ripk3 leading to formation", "ripk3 leading to formation of", "leading to formation of the", "to formation of the necrosome", "of the necrosome a", "the necrosome a necroptosis", "necrosome a necroptosis inducing", "a necroptosis inducing complex consisting", "necroptosis inducing complex consisting of", "inducing complex consisting of ripk1", "complex consisting of ripk1 and", "consisting of ripk1 and ripk3", "ripk1 and ripk3 tewari", "and ripk3 tewari m", "ripk3 tewari m &", "tewari m & dixit vm", "m & dixit vm 1995", "dixit vm 1995 fliss", "vm 1995 fliss pm", "1995 fliss pm &", "fliss pm & brune w", "pm & brune w 2012", "brune w 2012 sawai", "w 2012 sawai h", "2012 sawai h 2013", "sawai h 2013 moquin", "h 2013 moquin dm", "2013 moquin dm et", "moquin dm et al. 2013", "et al. 2013 kalai", "al. 2013 kalai m", "2013 kalai m et", "kalai m et al. 2002", "et al. 2002 cho", "al. 2002 cho ys", "2002 cho ys et", "cho ys et al. 2009", "et al. 2009 he", "al. 2009 he s", "2009 he s et", "he s et al. 2009", "et al. 2009 zhang", "al. 2009 zhang dw", "2009 zhang dw et", "dw et al. 2009", "et al. 2009 .", "al. 2009 . within", "2009 . within the complex", ". within the complex ii", "within the complex ii procaspase", "the complex ii procaspase 8", "complex ii procaspase 8 can", "ii procaspase 8 can also", "procaspase 8 can also form", "8 can also form heterodimers", "can also form heterodimers with", "also form heterodimers with cflip", "form heterodimers with cflip isoforms", "with cflip isoforms flip", "cflip isoforms flip long", "long l and", "l and flip short", "and flip short s", "s which are", "which are encoded by the", "are encoded by the nfkappab", "encoded by the nfkappab target", "by the nfkappab target gene", "the nfkappab target gene cflar", "target gene cflar irmler", "gene cflar irmler m", "cflar irmler m et", "irmler m et al. 1997", "et al. 1997 boatright", "al. 1997 boatright km", "1997 boatright km et", "boatright km et al. 2004", "et al. 2004 yu", "al. 2004 yu jw", "2004 yu jw et", "yu jw et al. 2009", "et al. 2009 pop", "al. 2009 pop c", "2009 pop c et", "pop c et al. 2011", "c et al. 2011 .", "et al. 2011 . flip", "al. 2011 . flip s", ". flip s appears", "flip s appears to", "s appears to act", "appears to act purely as", "to act purely as an", "act purely as an antagonist", "purely as an antagonist of", "as an antagonist of caspase", "an antagonist of caspase 8", "antagonist of caspase 8 activity", "of caspase 8 activity blocking", "caspase 8 activity blocking apoptotic", "8 activity blocking apoptotic but", "activity blocking apoptotic but promoting", "blocking apoptotic but promoting necroptotic", "apoptotic but promoting necroptotic cell", "but promoting necroptotic cell death", "necroptotic cell death feoktistova", "death feoktistova et", "feoktistova et al. 2011", "et al. 2011 . the", "al. 2011 . the regulatory", "2011 . the regulatory function", ". the regulatory function of", "the regulatory function of flip", "regulatory function of flip l", "of flip l has", "flip l has been", "l has been found", "has been found to differ", "been found to differ depending", "found to differ depending on", "to differ depending on its", "differ depending on its expression", "depending on its expression levels.", "on its expression levels. flip", "its expression levels. flip l", "levels. flip l was", "flip l was shown", "l was shown to", "was shown to inhibit death", "shown to inhibit death receptor", "inhibit death receptor dr", "receptor dr mediated", "dr mediated apoptosis only", "mediated apoptosis only when expressed", "apoptosis only when expressed at", "only when expressed at high", "when expressed at high levels", "at high levels while", "high levels while low", "levels while low cell", "while low cell levels of", "low cell levels of flip", "cell levels of flip l", "of flip l enhanced", "flip l enhanced dr", "l enhanced dr signaling", "enhanced dr signaling to apoptosis", "signaling to apoptosis boatright", "to apoptosis boatright km", "apoptosis boatright km et", "et al. 2004 okano", "al. 2004 okano h", "2004 okano h et", "okano h et al. 2003", "et al. 2003 yerbes", "al. 2003 yerbes r", "2003 yerbes r et", "yerbes r et al. 2011", "et al. 2011 yu", "al. 2011 yu jw", "2011 yu jw et", "et al. 2009 hughes", "al. 2009 hughes ma", "2009 hughes ma et", "hughes ma et al. 2016", "ma et al. 2016 .", "et al. 2016 . in", "al. 2016 . in addition", ". in addition caspase", "in addition caspase 8:flip", "addition caspase 8:flip l", "caspase 8:flip l heterodimer", "8:flip l heterodimer activity", "l heterodimer activity within", "heterodimer activity within the tradd:traf2:ripk1:fadd:casp8:flip", "activity within the tradd:traf2:ripk1:fadd:casp8:flip l", "the tradd:traf2:ripk1:fadd:casp8:flip l complex", "tradd:traf2:ripk1:fadd:casp8:flip l complex allowed", "l complex allowed cleavage", "complex allowed cleavage of ripk1", "allowed cleavage of ripk1 to", "cleavage of ripk1 to cause", "of ripk1 to cause the", "ripk1 to cause the dissociation", "to cause the dissociation of", "cause the dissociation of the", "the dissociation of the tradd:traf2:rip1:fadd:casp8", "of the tradd:traf2:rip1:fadd:casp8 thereby", "the tradd:traf2:rip1:fadd:casp8 thereby inhibiting", "tradd:traf2:rip1:fadd:casp8 thereby inhibiting ripk1", "thereby inhibiting ripk1 mediated necroptosis", "ripk1 mediated necroptosis feoktistova", "necroptosis feoktistova et", "et al. 2011 2012", "al. 2011 2012 .", "2011 2012 . tnf", "2012 . tnf \u03b1 can", ". tnf \u03b1 can also", "tnf \u03b1 can also activate", "\u03b1 can also activate sphingomyelinase", "also activate sphingomyelinase smase", "sphingomyelinase smase such", "smase such as smpd2", "as smpd2 3 proteins", "smpd2 3 proteins to", "3 proteins to catalyze", "proteins to catalyze hydrolysis of", "to catalyze hydrolysis of sphingomyeline", "catalyze hydrolysis of sphingomyeline into", "hydrolysis of sphingomyeline into ceramide", "sphingomyeline into ceramide adam", "into ceramide adam d", "ceramide adam d et", "d et al.1996 adam", "et al.1996 adam klages", "al.1996 adam klages s", "adam klages s et al.", "klages s et al. 1998", "et al. 1998 s\u00e9gui", "al. 1998 s\u00e9gui b", "1998 s\u00e9gui b et", "s\u00e9gui b et al. 2001", "b et al. 2001 .", "et al. 2001 . activation", "al. 2001 . activation of", "2001 . activation of neutral", ". activation of neutral smpd2", "activation of neutral smpd2 3", "of neutral smpd2 3 leads", "neutral smpd2 3 leads to", "smpd2 3 leads to an", "3 leads to an accumulation", "leads to an accumulation of", "to an accumulation of ceramide", "an accumulation of ceramide at", "accumulation of ceramide at the", "of ceramide at the cell", "ceramide at the cell surface", "at the cell surface and", "the cell surface and has", "cell surface and has proinflammatory", "surface and has proinflammatory effects.", "and has proinflammatory effects. however", "proinflammatory effects. however tnf", "effects. however tnf can", "however tnf can also", "tnf can also activate the", "can also activate the pro", "also activate the pro apoptotic", "activate the pro apoptotic acidic", "the pro apoptotic acidic smase", "pro apoptotic acidic smase via", "apoptotic acidic smase via caspase", "acidic smase via caspase 8", "smase via caspase 8 mediated", "via caspase 8 mediated activation", "caspase 8 mediated activation of", "8 mediated activation of caspase", "mediated activation of caspase 7", "activation of caspase 7 which", "of caspase 7 which in", "caspase 7 which in turn", "7 which in turn proteolytically", "which in turn proteolytically cleaves", "in turn proteolytically cleaves and", "turn proteolytically cleaves and activates", "proteolytically cleaves and activates the", "cleaves and activates the 72kda", "and activates the 72kda pro", "activates the 72kda pro a", "the 72kda pro a smase", "72kda pro a smase form", "a smase form edelmann", "smase form edelmann b", "form edelmann b et", "edelmann b et al. 2011", "b et al. 2011 .", "et al. 2011 . ceramide", "al. 2011 . ceramide induces", "2011 . ceramide induces anti", ". ceramide induces anti proliferative", "ceramide induces anti proliferative and", "induces anti proliferative and pro", "anti proliferative and pro apoptotic", "proliferative and pro apoptotic responses.", "and pro apoptotic responses. further", "apoptotic responses. further ceramide", "responses. further ceramide can", "further ceramide can be", "ceramide can be converted by", "can be converted by ceramidase", "be converted by ceramidase into", "converted by ceramidase into sphingosine", "ceramidase into sphingosine which", "into sphingosine which in", "sphingosine which in turn", "which in turn is phosphorylated", "in turn is phosphorylated by", "turn is phosphorylated by sphingosine", "is phosphorylated by sphingosine kinase", "phosphorylated by sphingosine kinase into", "by sphingosine kinase into sphingosine", "sphingosine kinase into sphingosine 1", "kinase into sphingosine 1 phosphate", "sphingosine 1 phosphate s1p", "1 phosphate s1p .", "phosphate s1p . s1p", "s1p . s1p exerts the", ". s1p exerts the opposite", "s1p exerts the opposite biological", "exerts the opposite biological effects", "the opposite biological effects to", "opposite biological effects to ceramide", "biological effects to ceramide by", "effects to ceramide by activating", "to ceramide by activating cytoprotective", "ceramide by activating cytoprotective signaling", "by activating cytoprotective signaling to", "activating cytoprotective signaling to promote", "cytoprotective signaling to promote cell", "signaling to promote cell growth", "to promote cell growth counteracting", "promote cell growth counteracting the", "cell growth counteracting the apoptotic", "growth counteracting the apoptotic stimuli", "the apoptotic stimuli cuvillier", "apoptotic stimuli cuvillier o", "stimuli cuvillier o et", "cuvillier o et al. 1996", "o et al. 1996 .", "et al. 1996 . thus", "1996 . thus tnf", ". thus tnf \u03b1", "thus tnf \u03b1 induced", "tnf \u03b1 induced tnfr1 activation", "\u03b1 induced tnfr1 activation leads", "induced tnfr1 activation leads to", "tnfr1 activation leads to divergent", "activation leads to divergent intracellular", "leads to divergent intracellular signaling", "to divergent intracellular signaling networks", "divergent intracellular signaling networks with", "intracellular signaling networks with extensive", "signaling networks with extensive cross", "networks with extensive cross talk", "with extensive cross talk between", "extensive cross talk between the", "cross talk between the pro", "talk between the pro apoptotic/necroptotic", "between the pro apoptotic/necroptotic pathway", "pro apoptotic/necroptotic pathway and", "apoptotic/necroptotic pathway and the", "pathway and the other", "the other nfkappab and", "other nfkappab and mapk", "nfkappab and mapk pathways", "and mapk pathways providing highly", "mapk pathways providing highly specific", "pathways providing highly specific cell", "providing highly specific cell responses", "highly specific cell responses initiated", "specific cell responses initiated by", "cell responses initiated by various", "responses initiated by various types", "initiated by various types of", "by various types of stimuli." ] }, { "record_id": "GLY_000594_1_1129", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "76009", "r hsa", "hsa 76009", "r hsa 76009" ] }, { "record_id": "GLY_000594_1_1129", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "platelet aggregation", "plug formation", "aggregation plug", "platelet aggregation plug", "aggregation plug formation", "platelet aggregation plug formation", "the tethering", "tethering of", "of platelets", "platelets to", "to the", "the site", "site of", "of vascular", "vascular injury", "injury is", "is the", "the first", "first step", "step in", "in the", "the formation", 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              ", ".
              mutations", "mutations in", "in nlrp3", "nlrp3 which", "which lead", "lead to", "to constitutive", "constitutive activation", "activation are", "are linked", "linked to", "to the", "the human", "human diseases", "diseases muckle", "muckle wells", "wells syndrome", "familial cold", "cold autoinflammatory", "autoinflammatory syndrome", "syndrome and", "and nomid", "ting et", "et al.", "al. 2006", "characterized by", "by skin", "skin rashes", "rashes and", "and other", "other symptoms", "symptoms associated", "associated with", "with generalized", "generalized inflammation.", "inflammation. the", "the cause", "cause of", "of these", "these symptoms", "symptoms is", "is uncontrolled", "uncontrolled il", "il 1", "1 beta", "beta production.", "production. multiple", "multiple studies", "studies have", "have shown", "shown that", "that activation", "activation of", "of the", "inflammasome by", "by particulate", "particulate activators", "e.g. hornung", "hornung et", "al. 2008", "requires phagocytosis", "but this", "this is", "is not", "not required", "required for", "for the", "the response", "response to", "to atp", "which is", "is mediated", "mediated by", "by the", "the p2x7", "p2x7 receptor", "kahlenberg &", "& dubyak", "and appears", "appears to", "to involve", "involve the", "the pannexin", "pannexin membrane", "membrane channel", "pellegrin &", "& suprenenant", "suprenenant 2006", "2006 .", ". direct", "direct binding", "binding of", "of activators", "activators to", "to nlrp3", "nlrp3 has", "has not", "not been", "been demonstrated", "demonstrated and", "and the", "the exact", "exact process", "process of", "of activation", "activation is", "is unclear", "though it", "is speculated", "speculated to", "involve changes", "changes in", "in conformation", "conformation that", "that free", "free the", "the nacht", "nacht domain", "domain for", "for oligomerization", "inohara &", "& nunez", "nunez 2001", "2003 .", "nlrp3 cryopyrin", "cryopyrin inflammasome", "inflammasome is currently", "is currently the", "currently the best", "the best characterized.", "best characterized. it", "characterized. it consists", "it consists of", "consists of nlrp3", "nlrp3 asc", "asc pycard", "pycard and", "and procaspase 1", "1 card8", "card8 cardinal", "cardinal is", "is also suggested", "also suggested to", "suggested to be", "to be a", "be a component.", "a component. it", "component. it is", "it is activated", "is activated by", "activated by a", "by a number", "a number of", "number of pathogens", "of pathogens and", "pathogens and bacterial", "and bacterial toxins", "bacterial toxins as", "toxins as well", "as well as", "well as diverse", "as diverse pamps", "pamps danger", "danger associated molecular", "associated molecular patterns", "patterns damps", "damps such", "such as hyaluronan", "as hyaluronan and", "hyaluronan and uric", "and uric acid", "acid and", "and exogenous irritants", "exogenous irritants such", "irritants such as", "such as silica", "as silica and", "silica and asbestos", "asbestos see", "see table s1", "table s1 schroder", "s1 schroder &", "schroder & tschopp", "tschopp 2010", "2010 .
              mutations", ".
              mutations in", "mutations in nlrp3", "in nlrp3 which", "nlrp3 which lead", "which lead to", "lead to constitutive", "to constitutive activation", "constitutive activation are", "activation are linked", "are linked to", "linked to the", "to the human", "the human diseases", "human diseases muckle", "diseases muckle wells", "muckle wells syndrome", "syndrome familial", "familial cold autoinflammatory", "cold autoinflammatory syndrome", "autoinflammatory syndrome and", "syndrome and nomid", "nomid ting", "ting et al.", "et al. 2006", "characterized by skin", "by skin rashes", "skin rashes and", "rashes and other", "and other symptoms", "other symptoms associated", "symptoms associated with", "associated with generalized", "with generalized inflammation.", "generalized inflammation. the", "inflammation. the cause", "the cause of", "cause of these", "of these symptoms", "these symptoms is", "symptoms is uncontrolled", "is uncontrolled il", "uncontrolled il 1", "il 1 beta", "1 beta production.", "beta production. multiple", "production. multiple studies", "multiple studies have", "studies have shown", "have shown that", "shown that activation", "that activation of", "activation of the", "of the nlrp3", "nlrp3 inflammasome by", "inflammasome by particulate", "by particulate activators", "activators e.g.", "e.g. hornung et", "hornung et al.", "et al. 2008", "2008 requires", "phagocytosis but", "but this is", "this is not", "is not required", "not required for", "required for the", "for the response", "the response to", "response to atp", "atp which", "which is mediated", "is mediated by", "mediated by the", "by the p2x7", "the p2x7 receptor", "receptor kahlenberg", "kahlenberg & dubyak", "dubyak 2004", "2004 and", "and appears to", "appears to involve", "to involve the", "involve the pannexin", "the pannexin membrane", "pannexin membrane channel", "channel pellegrin", "pellegrin & suprenenant", "& suprenenant 2006", "suprenenant 2006 .", "2006 . direct", ". direct binding", "direct binding of", "binding of activators", "of activators to", "activators to nlrp3", "to nlrp3 has", "nlrp3 has not", "has not been", "not been demonstrated", "been demonstrated and", "demonstrated and the", "and the exact", "the exact process", "exact process of", "process of activation", "of activation is", "activation is unclear", "unclear though", "though it is", "it is speculated", "is speculated to", "speculated to involve", "to involve changes", "involve changes in", "changes in conformation", "in conformation that", "conformation that free", "that free the", "free the nacht", "the nacht domain", "nacht domain for", "domain for oligomerization", "oligomerization inohara", "inohara & nunez", "& nunez 2001", "2001 2003", "the nlrp3 cryopyrin", "cryopyrin inflammasome is", "inflammasome is currently the", "is currently the best", "currently the best characterized.", "the best characterized. it", "best characterized. it consists", "characterized. it consists of", "it consists of nlrp3", "of nlrp3 asc", "pycard and procaspase", "procaspase 1 card8", "cardinal is also", "is also suggested to", "also suggested to be", "suggested to be a", "to be a component.", "be a component. it", "a component. it is", "component. it is activated", "it is activated by", "is activated by a", "activated by a number", "by a number of", "a number of pathogens", "number of pathogens and", "of pathogens and bacterial", "pathogens and bacterial toxins", "and bacterial toxins as", "bacterial toxins as well", "toxins as well as", "as well as diverse", "well as diverse pamps", "diverse pamps danger", "pamps danger associated", "danger associated molecular patterns", "molecular patterns damps", "damps such as", "such as hyaluronan and", "as hyaluronan and uric", "hyaluronan and uric acid", "uric acid and", "acid and exogenous", "and exogenous irritants such", "exogenous irritants such as", "irritants such as silica", "such as silica and", "as silica and asbestos", "and asbestos see", "asbestos see table", "see table s1 schroder", "table s1 schroder &", "s1 schroder & tschopp", "& tschopp 2010", "tschopp 2010 .
              ", "2010 .
              mutations in", ".
              mutations in nlrp3", "mutations in nlrp3 which", "in nlrp3 which lead", "nlrp3 which lead to", "which lead to constitutive", "lead to constitutive activation", "to constitutive activation are", "constitutive activation are linked", "activation are linked to", "are linked to the", "linked to the human", "to the human diseases", "the human diseases muckle", "human diseases muckle wells", "diseases muckle wells syndrome", "wells syndrome familial", "syndrome familial cold", "familial cold autoinflammatory syndrome", "cold autoinflammatory syndrome and", "autoinflammatory syndrome and nomid", "and nomid ting", "nomid ting et", "ting et al. 2006", "2006 characterized", "characterized by skin rashes", "by skin rashes and", "skin rashes and other", "rashes and other symptoms", "and other symptoms associated", "other symptoms associated with", "symptoms associated with generalized", "associated with generalized inflammation.", "with generalized inflammation. the", "generalized inflammation. the cause", "inflammation. the cause of", "the cause of these", "cause of these symptoms", "of these symptoms is", "these symptoms is uncontrolled", "symptoms is uncontrolled il", "is uncontrolled il 1", "uncontrolled il 1 beta", "il 1 beta production.", "1 beta production. multiple", "beta production. multiple studies", "production. multiple studies have", "multiple studies have shown", "studies have shown that", "have shown that activation", "shown that activation of", "that activation of the", "activation of the nlrp3", "of the nlrp3 inflammasome", "the nlrp3 inflammasome by", "nlrp3 inflammasome by particulate", "inflammasome by particulate activators", "particulate activators e.g.", "activators e.g. hornung", "e.g. hornung et al.", "hornung et al. 2008", "al. 2008 requires", "2008 requires phagocytosis", "requires phagocytosis but", "phagocytosis but this", "but this is not", "this is not required", "is not required for", "not required for the", "required for the response", "for the response to", "the response to atp", "to atp which", "atp which is", "which is mediated by", "is mediated by the", "mediated by the p2x7", "by the p2x7 receptor", "p2x7 receptor kahlenberg", "receptor kahlenberg &", "& dubyak 2004", "2004 and appears", "and appears to involve", "appears to involve the", "to involve the pannexin", "involve the pannexin membrane", "the pannexin membrane channel", "membrane channel pellegrin", "channel pellegrin &", "pellegrin & suprenenant 2006", "& suprenenant 2006 .", "suprenenant 2006 . direct", "2006 . direct binding", ". direct binding of", "direct binding of activators", "binding of activators to", "of activators to nlrp3", "activators to nlrp3 has", "to nlrp3 has not", "nlrp3 has not been", "has not been demonstrated", "not been demonstrated and", "been demonstrated and the", "demonstrated and the exact", "and the exact process", "the exact process of", "exact process of activation", "process of activation is", "of activation is unclear", "is unclear though", "unclear though it", "though it is speculated", "it is speculated to", "is speculated to involve", "speculated to involve changes", "to involve changes in", "involve changes in conformation", "changes in conformation that", "in conformation that free", "conformation that free the", "that free the nacht", "free the nacht domain", "the nacht domain for", "nacht domain for oligomerization", "for oligomerization inohara", "oligomerization inohara &", "inohara & nunez 2001", "nunez 2001 2003", "2001 2003 .", "nlrp3 cryopyrin inflammasome", "cryopyrin inflammasome is currently", "inflammasome is currently the best", "is currently the best characterized.", "currently the best characterized. it", "the best characterized. it consists", "best characterized. it consists of", "characterized. it consists of nlrp3", "consists of nlrp3 asc", "nlrp3 asc pycard", "asc pycard and", "pycard and procaspase 1", "and procaspase 1 card8", "1 card8 cardinal", "card8 cardinal is", "cardinal is also suggested", "is also suggested to be", "also suggested to be a", "suggested to be a component.", "to be a component. it", "be a component. it is", "a component. it is activated", "component. it is activated by", "it is activated by a", "is activated by a number", "activated by a number of", "by a number of pathogens", "a number of pathogens and", "number of pathogens and bacterial", "of pathogens and bacterial toxins", "pathogens and bacterial toxins as", "and bacterial toxins as well", "bacterial toxins as well as", "toxins as well as diverse", "as well as diverse pamps", "as diverse pamps danger", "diverse pamps danger associated", "pamps danger associated molecular", "associated molecular patterns damps", "patterns damps such", "damps such as hyaluronan", "such as hyaluronan and uric", "as hyaluronan and uric acid", "and uric acid and", "uric acid and exogenous", "acid and exogenous irritants", "and exogenous irritants such as", "exogenous irritants such as silica", "irritants such as silica and", "such as silica and asbestos", "silica and asbestos see", "and asbestos see table", "asbestos see table s1", "see table s1 schroder &", "table s1 schroder & tschopp", "schroder & tschopp 2010", "& tschopp 2010 .
              ", "tschopp 2010 .
              mutations", "2010 .
              mutations in nlrp3", ".
              mutations in nlrp3 which", "mutations in nlrp3 which lead", "in nlrp3 which lead to", "nlrp3 which lead to constitutive", "which lead to constitutive activation", "lead to constitutive activation are", "to constitutive activation are linked", "constitutive activation are linked to", "activation are linked to the", "are linked to the human", "linked to the human diseases", "to the human diseases muckle", "the human diseases muckle wells", "human diseases muckle wells syndrome", "muckle wells syndrome familial", "wells syndrome familial cold", "syndrome familial cold autoinflammatory", "familial cold autoinflammatory syndrome and", "cold autoinflammatory syndrome and nomid", "syndrome and nomid ting", "and nomid ting et", "nomid ting et al.", "al. 2006 characterized", "2006 characterized by", "characterized by skin rashes and", "by skin rashes and other", "skin rashes and other symptoms", "rashes and other symptoms associated", "and other symptoms associated with", "other symptoms associated with generalized", "symptoms associated with generalized inflammation.", "associated with generalized inflammation. the", "with generalized inflammation. the cause", "generalized inflammation. the cause of", "inflammation. the cause of these", "the cause of these symptoms", "cause of these symptoms is", "of these symptoms is uncontrolled", "these symptoms is uncontrolled il", "symptoms is uncontrolled il 1", "is uncontrolled il 1 beta", "uncontrolled il 1 beta production.", "il 1 beta production. multiple", "1 beta production. multiple studies", "beta production. multiple studies have", "production. multiple studies have shown", "multiple studies have shown that", "studies have shown that activation", "have shown that activation of", "shown that activation of the", "that activation of the nlrp3", "activation of the nlrp3 inflammasome", "of the nlrp3 inflammasome by", "the nlrp3 inflammasome by particulate", "nlrp3 inflammasome by particulate activators", "by particulate activators e.g.", "particulate activators e.g. hornung", "activators e.g. hornung et", "e.g. hornung et al. 2008", "et al. 2008 requires", "al. 2008 requires phagocytosis", "requires phagocytosis but this", "phagocytosis but this is", "but this is not required", "this is not required for", "is not required for the", "not required for the response", "required for the response to", "for the response to atp", "response to atp which", "to atp which is", "atp which is mediated", "which is mediated by the", "is mediated by the p2x7", "mediated by the p2x7 receptor", "the p2x7 receptor kahlenberg", "p2x7 receptor kahlenberg &", "receptor kahlenberg & dubyak", "kahlenberg & dubyak 2004", "dubyak 2004 and", "2004 and appears to", "and appears to involve the", "appears to involve the pannexin", "to involve the pannexin membrane", "involve the pannexin membrane channel", "pannexin membrane channel pellegrin", "membrane channel pellegrin &", "channel pellegrin & suprenenant", "pellegrin & suprenenant 2006 .", "& suprenenant 2006 . direct", "suprenenant 2006 . direct binding", "2006 . direct binding of", ". direct binding of activators", "direct binding of activators to", "binding of activators to nlrp3", "of activators to nlrp3 has", "activators to nlrp3 has not", "to nlrp3 has not been", "nlrp3 has not been demonstrated", "has not been demonstrated and", "not been demonstrated and the", "been demonstrated and the exact", "demonstrated and the exact process", "and the exact process of", "the exact process of activation", "exact process of activation is", "process of activation is unclear", "activation is unclear though", "is unclear though it", "unclear though it is", "though it is speculated to", "it is speculated to involve", "is speculated to involve changes", "speculated to involve changes in", "to involve changes in conformation", "involve changes in conformation that", "changes in conformation that free", "in conformation that free the", "conformation that free the nacht", "that free the nacht domain", "free the nacht domain for", "the nacht domain for oligomerization", "domain for oligomerization inohara", "for oligomerization inohara &", "oligomerization inohara & nunez", "& nunez 2001 2003", "nunez 2001 2003 ." ] }, { "record_id": "GLY_000594_1_1132", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "879518", "r hsa", "hsa 879518", "r hsa 879518" ] }, { "record_id": "GLY_000594_1_1132", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transport of", "of organic", "organic anions", "transport of organic", "of organic anions", "transport of organic anions", "organic anion", "anion transporting", "transporting polypeptides", "are membrane", "membrane transport", "transport proteins", "proteins that", "that mediate", "mediate the", "the sodium", "sodium independent", "independent transport", "of a", "a wide", "wide range", "range of", "of 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"threonine degradation is therefore", "degradation is therefore annotated", "is therefore annotated here", "therefore annotated here as", "annotated here as the", "here as the conversion", "as the conversion of", "the conversion of threonine", "conversion of threonine to", "of threonine to 2", "threonine to 2 oxobutanoate", "to 2 oxobutanoate and", "2 oxobutanoate and the", "oxobutanoate and the related", "and the related conversion", "the related conversion of", "related conversion of 2", "conversion of 2 iminobutanoate", "of 2 iminobutanoate to", "2 iminobutanoate to 2", "iminobutanoate to 2 oxobutanoate.", "in many mammals threonine", "many mammals threonine can", "mammals threonine can be", "threonine can be catabolized either", "can be catabolized either via", "be catabolized either via mitochondrial", "catabolized either via mitochondrial l", "either via mitochondrial l threonine", "via mitochondrial l threonine 3", "mitochondrial l threonine 3 dehydrogenase", "threonine 3 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              for", "studied.

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              all e", "substrate.
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              for", "thoroughly studied.

              for reviews", "studied.

              for reviews of", "reviews of the", "of the ntpdase", "the ntpdase family", "family please", "please refer to", "refer to robson", "to robson et", "robson et al.", "et al. 2006", "al. 2006 and", "2006 and zimmermann", "and zimmermann et", "zimmermann et al.", "et al. 2012.", "the ectonucleoside triphosphate diphosphatase", "triphosphate diphosphatase e", "diphosphatase e ntpdase", "ntpdase family of", "family of ectonucleotidases", "of ectonucleotidases includes 8", "ectonucleotidases includes 8 enzymes:", "includes 8 enzymes: ntpdase1", "enzymes: ntpdase1 encoded", "ntpdase1 encoded by", "encoded by the entpd1", "by the entpd1 gene", "gene ntpdase2", "ntpdase2 encoded by", "encoded by the entpd2", "by the entpd2 gene", "gene ntpdase3", "ntpdase3 encoded by", "encoded by the entpd3", "by the entpd3 gene", "gene ntpdase4", "ntpdase4 encoded by", "encoded by the entpd4", "by the entpd4 gene", "gene ntpdase5", "ntpdase5 encoded by", "encoded by the entpd5", "by the entpd5 gene", "gene ntpdase6", "ntpdase6 encoded by", "encoded by the entpd6", "by the entpd6 gene", "gene ntpdase7", "ntpdase7 encoded by", "encoded by the entpd7", "by the entpd7 gene", "entpd7 gene and", "gene and ntpdase8", "and ntpdase8 encoded", "ntpdase8 encoded by", "encoded by the entpd8", "by the entpd8 gene", "the entpd8 gene .", "entpd8 gene . ntpdases", "gene . ntpdases hydrolyze", ". ntpdases hydrolyze nucleoside", "ntpdases hydrolyze nucleoside triphosphates", "hydrolyze nucleoside triphosphates and", "nucleoside triphosphates and nucleoside", "triphosphates and nucleoside diphosphates", "nucleoside diphosphates producing", "diphosphates producing the", "producing the corresponding nucleoside", "the corresponding nucleoside monophosphates", "corresponding nucleoside monophosphates as", "nucleoside monophosphates as final", "monophosphates as final products.", "as final products. different", "final products. different family", "products. different family members", "different family members show", "family members show different", "members show different specificity", "show different specificity for", "different specificity for particular", "specificity for particular nucleotides.", "for particular nucleotides. ntpdases", "particular nucleotides. ntpdases are", "nucleotides. ntpdases are involved", "ntpdases are involved in", "are involved in various", "involved in various biological", "in various biological processes", "biological processes such", "processes such as", "as hemostasis immune", "hemostasis immune response", "immune response and development", "response and development of", "and development of the", "development of the nervous", "of the nervous system.", "the nervous system.
              the", "nervous system.
              the catalytic", "system.
              the catalytic domain", "
              the catalytic domain of", "catalytic domain of ntpdases", "domain of ntpdases is", "of ntpdases is contained", "ntpdases is contained within", "is contained within the", "contained within the loop", "within the loop formed", "the loop formed by", "loop formed by a", "formed by a cluster", "by a cluster of", "a cluster of apyrase", "cluster of apyrase conserved", "of apyrase conserved regions", "conserved regions acrs", "regions acrs .", "acrs . all family", ". all family members", "all family members require", "family members require divalent", "members require divalent cations", "divalent cations such", "cations such as", "as calcium ca2+", "ca2+ or magnesium", "or magnesium mg2+", "ions for catalytic", "for catalytic activity. the", "catalytic activity. the hydrolysis", "activity. the hydrolysis involves", "the hydrolysis involves a", "hydrolysis involves a nucleophilic", "involves a nucleophilic attack", "a nucleophilic attack of", "nucleophilic attack of a", "attack of a water", "of a water molecule", "a water molecule on", "water molecule on the", "molecule on the terminal", "on the terminal phosphate", "the terminal phosphate of", "terminal phosphate of a", "phosphate of a nucleotide", "of a nucleotide substrate.
              all", "a nucleotide substrate.
              all e", "nucleotide substrate.
              all e ntpdase", "substrate.
              all e ntpdase family", "e ntpdase family members", "ntpdase family members are", "family members are transmembrane", "members are transmembrane proteins", "transmembrane proteins associated", "proteins associated with", "associated with either plasma", "with either plasma membrane", "plasma membrane ntpdase1", "ntpdase2 ntpdase3 and", "and ntpdase8 or", "ntpdase8 or organelle", "organelle membranes ntpdase4", "membranes ntpdase4 and", "ntpdase4 and ntpdase7 .", "and ntpdase7 . two", "ntpdase7 . two family", ". two family members", "family members ntpdase5", "members ntpdase5 and", "and ntpdase6 can", "ntpdase6 can be", "can be secreted into", "be secreted into extracellular", "secreted into extracellular space", "into extracellular space following", "extracellular space following a", "space following a proteolytic", "following a proteolytic cleavage", "a proteolytic cleavage from", "proteolytic cleavage from the", "cleavage from the plasma", "from the plasma membrane.", "the plasma membrane. ntpdases", "plasma membrane. ntpdases hydrolyze", "membrane. ntpdases hydrolyze exocytoplasmic", "ntpdases hydrolyze exocytoplasmic nucleotides", "exocytoplasmic nucleotides thus", "nucleotides thus regulating", "thus regulating the availability", "regulating the availability of", "the availability of ligands", "availability of ligands for", "of ligands for purinergic", "ligands for purinergic receptors.", "for purinergic receptors. glycosylation", "purinergic receptors. glycosylation and", "receptors. glycosylation and oligomerization", "glycosylation and oligomerization are", "and oligomerization are involved", "oligomerization are involved in", "are involved in the", "involved in the regulation", "in the regulation of", "the regulation of ntpdases", "of ntpdases but", "ntpdases but have", "but have not been", "have not been thoroughly", "not been thoroughly studied.

              for", "been thoroughly studied.

              for reviews", "thoroughly studied.

              for reviews of", "studied.

              for reviews of the", "reviews of the ntpdase", "of the ntpdase family", "ntpdase family please", "family please refer", "please refer to robson", "refer to robson et", "to robson et al.", "robson et al. 2006", "et al. 2006 and", "al. 2006 and zimmermann", "2006 and zimmermann et", "and zimmermann et al.", "zimmermann et al. 2012.", "ectonucleoside triphosphate diphosphatase e", "triphosphate diphosphatase e ntpdase", "diphosphatase e ntpdase family", "e ntpdase family of", "ntpdase family of ectonucleotidases", "family of ectonucleotidases includes", "of ectonucleotidases includes 8 enzymes:", "ectonucleotidases includes 8 enzymes: ntpdase1", "8 enzymes: ntpdase1 encoded", "enzymes: ntpdase1 encoded by", "ntpdase1 encoded by the", "encoded by the entpd1 gene", "entpd1 gene ntpdase2", "ntpdase2 encoded by the", "encoded by the entpd2 gene", "entpd2 gene ntpdase3", "ntpdase3 encoded by the", "encoded by the entpd3 gene", "entpd3 gene ntpdase4", "ntpdase4 encoded by the", "encoded by the entpd4 gene", "entpd4 gene ntpdase5", "ntpdase5 encoded by the", "encoded by the entpd5 gene", "entpd5 gene ntpdase6", "ntpdase6 encoded by the", "encoded by the entpd6 gene", "entpd6 gene ntpdase7", "ntpdase7 encoded by the", "encoded by the entpd7 gene", "the entpd7 gene and", "entpd7 gene and ntpdase8", "and ntpdase8 encoded by", "ntpdase8 encoded by the", "encoded by the entpd8 gene", "by the entpd8 gene .", "the entpd8 gene . ntpdases", "entpd8 gene . ntpdases hydrolyze", "gene . ntpdases hydrolyze nucleoside", ". ntpdases hydrolyze nucleoside triphosphates", "ntpdases hydrolyze nucleoside triphosphates and", "hydrolyze nucleoside triphosphates and nucleoside", "nucleoside triphosphates and nucleoside diphosphates", "and nucleoside diphosphates producing", "nucleoside diphosphates producing the", "diphosphates producing the corresponding", "producing the corresponding nucleoside monophosphates", "the corresponding nucleoside monophosphates as", "corresponding nucleoside monophosphates as final", "nucleoside monophosphates as final products.", "monophosphates as final products. different", "as final products. different family", "final products. different family members", "products. different family members show", "different family members show different", "family members show different specificity", "members show different specificity for", "show different specificity for particular", "different specificity for particular nucleotides.", "specificity for particular nucleotides. ntpdases", "for particular nucleotides. ntpdases are", "particular nucleotides. ntpdases are involved", "nucleotides. ntpdases are involved in", "ntpdases are involved in various", "are involved in various biological", "involved in various biological processes", "various biological processes such", "biological processes such as", "processes such as hemostasis", "such as hemostasis immune", "as hemostasis immune response", "hemostasis immune response and", "immune response and development of", "response and development of the", "and development of the nervous", "development of the nervous system.", "of the nervous system.
              the", "the nervous system.
              the catalytic", "nervous system.
              the catalytic domain", "system.
              the catalytic domain of", "
              the catalytic domain of ntpdases", "catalytic domain of ntpdases is", "domain of ntpdases is contained", "of ntpdases is contained within", "ntpdases is contained within the", "is contained within the loop", "contained within the loop formed", "within the loop formed by", "the loop formed by a", "loop formed by a cluster", "formed by a cluster of", "by a cluster of apyrase", "a cluster of apyrase conserved", "cluster of apyrase conserved regions", "apyrase conserved regions acrs", "conserved regions acrs .", "regions acrs . all", "acrs . all family members", ". all family members require", "all family members require divalent", "family members require divalent cations", "require divalent cations such", "divalent cations such as", "cations such as calcium", "such as calcium ca2+", "calcium ca2+ or", "magnesium mg2+ ions", "mg2+ ions for", "ions for catalytic activity.", "for catalytic activity. the hydrolysis", "catalytic activity. the hydrolysis involves", "activity. the hydrolysis involves a", "the hydrolysis involves a nucleophilic", "hydrolysis involves a nucleophilic attack", "involves a nucleophilic attack of", "a nucleophilic attack of a", "nucleophilic attack of a water", "attack of a water molecule", "of a water molecule on", "a water molecule on the", "water molecule on the terminal", "molecule on the terminal phosphate", "on the terminal phosphate of", "the terminal phosphate of a", "terminal phosphate of a nucleotide", "phosphate of a nucleotide substrate.
              all", "of a nucleotide substrate.
              all e", "a nucleotide substrate.
              all e ntpdase", "nucleotide substrate.
              all e ntpdase family", "substrate.
              all e ntpdase family members", "e ntpdase family members are", "ntpdase family members are transmembrane", "family members are transmembrane proteins", "are transmembrane proteins associated", "transmembrane proteins associated with", "proteins associated with either", "associated with either plasma membrane", "either plasma membrane ntpdase1", "membrane ntpdase1 ntpdase2", "ntpdase1 ntpdase2 ntpdase3", "ntpdase2 ntpdase3 and ntpdase8", "ntpdase3 and ntpdase8 or", "and ntpdase8 or organelle", "ntpdase8 or organelle membranes", "or organelle membranes ntpdase4", "organelle membranes ntpdase4 and", "membranes ntpdase4 and ntpdase7", "ntpdase4 and ntpdase7 . two", "and ntpdase7 . two family", "ntpdase7 . two family members", "two family members ntpdase5", "family members ntpdase5 and", "members ntpdase5 and ntpdase6", "ntpdase5 and ntpdase6 can", "and ntpdase6 can be", "ntpdase6 can be secreted", "can be secreted into extracellular", "be secreted into extracellular space", "secreted into extracellular space following", "into extracellular space following a", "extracellular space following a proteolytic", "space following a proteolytic cleavage", "following a proteolytic cleavage from", "a proteolytic cleavage from the", "proteolytic cleavage from the plasma", "cleavage from the plasma membrane.", "from the plasma membrane. ntpdases", "the plasma membrane. ntpdases hydrolyze", "plasma membrane. ntpdases hydrolyze exocytoplasmic", "membrane. ntpdases hydrolyze exocytoplasmic nucleotides", "hydrolyze exocytoplasmic nucleotides thus", "exocytoplasmic nucleotides thus regulating", "nucleotides thus regulating the", "thus regulating the availability of", "regulating the availability of ligands", "the availability of ligands for", "availability of ligands for purinergic", "of ligands for purinergic receptors.", "ligands for purinergic receptors. glycosylation", "for purinergic receptors. glycosylation and", "purinergic receptors. glycosylation and oligomerization", "receptors. glycosylation and oligomerization are", "glycosylation and oligomerization are involved", "and oligomerization are involved in", "oligomerization are involved in the", "are involved in the regulation", "involved in the regulation of", "in the regulation of ntpdases", "regulation of ntpdases but", "of ntpdases but have", "ntpdases but have not", "but have not been thoroughly", "have not been thoroughly studied.

              for", "not been thoroughly studied.

              for reviews", "been thoroughly studied.

              for reviews of", "thoroughly studied.

              for reviews of the", "studied.

              for reviews of the ntpdase", "reviews of the ntpdase family", "the ntpdase family please", "ntpdase family please refer", "family please refer to", "please refer to robson et", "refer to robson et al.", "to robson et al. 2006", "robson et al. 2006 and", "et al. 2006 and zimmermann", "al. 2006 and zimmermann et", "2006 and zimmermann et al.", "and zimmermann et al. 2012." ] }, { "record_id": "GLY_000594_1_1138", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8851708", "r hsa", "hsa 8851708", "r hsa 8851708" ] }, { "record_id": "GLY_000594_1_1138", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by fgfr2", "fgfr2 iiia", "iiia tm", "signaling by fgfr2", "by fgfr2 iiia", "fgfr2 iiia tm", "signaling by fgfr2 iiia", "by fgfr2 iiia tm", "signaling by fgfr2 iiia tm", "a soluble", "soluble truncated", "truncated form", "form of", "of fgfr2", "fgfr2 is", "is aberrantly", "aberrantly expressed", "expressed in", "in an", "an apert", "apert syndrome", "syndrome mouse", "mouse model", "model and", "and inhibits", "inhibits fgfr", "fgfr signaling", "signaling in", "in vitro", "vitro and", "and in", "in vivo.", "this variant", "termed fgfr", "fgfr iiia", "arises from", "from an", "an misspliced", "misspliced transcript", "transcript that", "that fuses", "fuses exon", "exon 7", "7 to", "to exon", "exon 10", "10 and", "and that", "that escapes", "escapes nonsense", "nonsense mediated", "mediated decay.", "tm may", "may inhibit", "inhibit signaling", "by sequestering", "sequestering fgf", "fgf ligand", "ligand and/or", "and/or by", "by forming", "forming nonfunctional", "nonfunctional heterodimers", "heterodimers with", "with full", "full length", "length receptors", "receptors at", "at the", "the cell", "cell surface", "wheldon et", "et al", "2011 .", "a soluble truncated", "soluble truncated form", "truncated form of", "form of fgfr2", "of fgfr2 is", "fgfr2 is aberrantly", "is aberrantly expressed", "aberrantly expressed in", "expressed in an", "in an apert", "an apert syndrome", "apert syndrome mouse", "syndrome mouse model", "mouse model and", "model and inhibits", "and inhibits fgfr", "inhibits fgfr signaling", "fgfr signaling in", "signaling in vitro", "in vitro and", "vitro and in", "and in vivo.", "vivo. this", "variant termed", "termed fgfr iiia", "fgfr iiia tm", "tm arises", "arises from an", "from an misspliced", "an misspliced transcript", "misspliced transcript that", "transcript that fuses", "that fuses exon", "fuses exon 7", "exon 7 to", "7 to exon", "to exon 10", "exon 10 and", "10 and that", "and that escapes", "that escapes nonsense", "escapes nonsense mediated", "nonsense mediated decay.", "decay. fgfr2", "iiia tm may", "tm may inhibit", "may inhibit signaling", "inhibit signaling by", "signaling by sequestering", "by sequestering fgf", "sequestering fgf ligand", "fgf ligand and/or", "ligand and/or by", "and/or by forming", "by forming nonfunctional", "forming nonfunctional heterodimers", "nonfunctional heterodimers with", "heterodimers with full", "with full length", "full length receptors", "length receptors at", "receptors at the", "at the cell", "the cell surface", "surface wheldon", "wheldon et al", "al 2011", "a soluble truncated form", "soluble truncated form of", "truncated form of fgfr2", "form of fgfr2 is", "of fgfr2 is aberrantly", "fgfr2 is aberrantly expressed", "is aberrantly expressed in", "aberrantly expressed in an", "expressed in an apert", "in an apert syndrome", "an apert syndrome mouse", "apert syndrome mouse model", "syndrome mouse model and", "mouse model and inhibits", "model and inhibits fgfr", "and inhibits fgfr signaling", "inhibits fgfr signaling in", "fgfr signaling in vitro", "signaling in vitro and", "in vitro and in", "vitro and in vivo.", "in vivo. this", "vivo. this variant", "this variant termed", "variant termed fgfr", "termed fgfr iiia tm", "iiia tm arises", "tm arises from", "arises from an misspliced", "from an misspliced transcript", "an misspliced transcript that", "misspliced transcript that fuses", "transcript that fuses exon", "that fuses exon 7", "fuses exon 7 to", "exon 7 to exon", "7 to exon 10", "to exon 10 and", "exon 10 and that", "10 and that escapes", "and that escapes nonsense", "that escapes nonsense mediated", "escapes nonsense mediated decay.", "mediated decay. fgfr2", "decay. fgfr2 iiia", "fgfr2 iiia tm may", "iiia tm may inhibit", "tm may inhibit signaling", "may inhibit signaling by", "inhibit signaling by sequestering", "signaling by sequestering fgf", "by sequestering fgf ligand", "sequestering fgf ligand and/or", "fgf ligand and/or by", "ligand and/or by forming", "and/or by forming nonfunctional", "by forming nonfunctional heterodimers", "forming nonfunctional heterodimers with", "nonfunctional heterodimers with full", "heterodimers with full length", "with full length receptors", "full length receptors at", "length receptors at the", "receptors at the cell", "at the cell surface", "cell surface wheldon", "surface wheldon et", "et al 2011", "al 2011 .", "a soluble truncated form of", "soluble truncated form of fgfr2", "truncated form of fgfr2 is", "form of fgfr2 is aberrantly", "of fgfr2 is aberrantly expressed", "fgfr2 is aberrantly expressed in", "is aberrantly expressed in an", "aberrantly expressed in an apert", "expressed in an apert syndrome", "in an apert syndrome mouse", "an apert syndrome mouse model", "apert syndrome mouse model and", "syndrome mouse model and inhibits", "mouse model and inhibits fgfr", "model and inhibits fgfr signaling", "and inhibits fgfr signaling in", "inhibits fgfr signaling in vitro", "fgfr signaling in vitro and", "signaling in vitro and in", "in vitro and in vivo.", "and in vivo. this", "in vivo. this variant", "this variant termed fgfr", "variant termed fgfr iiia", "fgfr iiia tm arises", "iiia tm arises from", "tm arises from an", "arises from an misspliced transcript", "from an misspliced transcript that", "an misspliced transcript that fuses", "misspliced transcript that fuses exon", "transcript that fuses exon 7", "that fuses exon 7 to", "fuses exon 7 to exon", "exon 7 to exon 10", "7 to exon 10 and", "to exon 10 and that", "exon 10 and that escapes", "10 and that escapes nonsense", "and that escapes nonsense mediated", "that escapes nonsense mediated decay.", "nonsense mediated decay. fgfr2", "mediated decay. fgfr2 iiia", "decay. fgfr2 iiia tm", "fgfr2 iiia tm may inhibit", "iiia tm may inhibit signaling", "tm may inhibit signaling by", "may inhibit signaling by sequestering", "inhibit signaling by sequestering fgf", "signaling by sequestering fgf ligand", "by sequestering fgf ligand and/or", "sequestering fgf ligand and/or by", "fgf ligand and/or by forming", "ligand and/or by forming nonfunctional", "and/or by forming nonfunctional heterodimers", "by forming nonfunctional heterodimers with", "forming nonfunctional heterodimers with full", "nonfunctional heterodimers with full length", "heterodimers with full length receptors", "with full length receptors at", "full length receptors at the", "length receptors at the cell", "receptors at the cell surface", "the cell surface wheldon", "cell surface wheldon et", "surface wheldon et al", "wheldon et al 2011", "et al 2011 ." ] }, { "record_id": "GLY_000594_1_1139", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8851805", "r hsa", "hsa 8851805", "r hsa 8851805" ] }, { "record_id": "GLY_000594_1_1139", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "met activates", "activates ras", "ras signaling", "met activates ras", "activates ras signaling", "met activates ras signaling", "activated met", "met receptor", "receptor recruits", "recruits the", "the ras", "ras guanyl", "guanyl nucleotide", "nucleotide exchange", "exchange factor", "sos1 indirectly", "either through", "through the", "the grb2", "grb2 adapter", "ponzetto et", "et al.", "al. 1994", "fournier et", "al. 1996", "shen and", "and novak", "novak 1997", "besser et", "al. 1997", "weidner et", "or shc1", "shc1 and", "and grb2", "pelicci et", "al. 1995", "or ranbp9", "wang et", "al. 2002", "al. 2004", "2004 .", ". association", "association of", "of sos1", "sos1 with", "with the", "the activated", "receptor complex", "complex leads", "leads to", "to exchange", "exchange of", "of gdp", "gdp to", "to gtp", "gtp on", "on ras", "ras and", "and activation", "activation of", "of ras", "2004 .
              ptpn11", "may contribute", "contribute to", "to activation", "signaling downstream", "downstream of", "of met", "schaeper et", "al. 2000", "furcht et", "al. 2014", "2014 .
              sustained", ".
              sustained activation", "of mapk1", "and mapk3", "met activated", "activated ras", "ras may", "may require", "require met", "met endocytosis", "endocytosis and", "and signaling", "signaling from", "from endosomes", "peschard et", "al. 2001", "hammond et", "petrelli et", "kermorgant and", "and parker", "parker 2008", "2008 .
              binding", ".
              binding of", "met to", "to muc20", "muc20 or", "or ranbp10", "ranbp10 interferes", "interferes with", "with ras", "ras activation", "higuchi et", "activated met receptor", "met receptor recruits", "receptor recruits the", "recruits the ras", "the ras guanyl", "ras guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange factor", "factor gef", "gef sos1", "indirectly either", "either through the", "through the grb2", "the grb2 adapter", "adapter ponzetto", "ponzetto et al.", "et al. 1994", "1994 fournier", "fournier et al.", "et al. 1996", "1996 shen", "shen and novak", "and novak 1997", "1997 besser", "besser et al.", "et al. 1997", "gab1 weidner", "weidner et al.", "1996 or", "or shc1 and", "shc1 and grb2", "grb2 pelicci", "pelicci et al.", "et al. 1995", "ranbp9 wang", "wang et al.", "et al. 2002", "2002 wang", "et al. 2004", "al. 2004 .", "2004 . association", ". association of", "association of sos1", "of sos1 with", "sos1 with the", "with the activated", "the activated met", "met receptor complex", "receptor complex leads", "complex leads to", "leads to exchange", "to exchange of", "exchange of gdp", "of gdp to", "gdp to gtp", "to gtp on", "gtp on ras", "on ras and", "ras and activation", "and activation of", "activation of ras", "of ras signaling", "signaling pelicci", "1995 besser", "1997 shen", "1997 wang", "al. 2004 .
              ptpn11", ".
              ptpn11 shp2", "shp2 may", "may contribute to", "contribute to activation", "to activation of", "ras signaling downstream", "signaling downstream of", "downstream of met", "met schaeper", "schaeper et al.", "et al. 2000", "2000 furcht", "furcht et al.", "et al. 2014", "al. 2014 .
              sustained", "2014 .
              sustained activation", ".
              sustained activation of", "activation of mapk1", "mapk1 erk2", "erk2 and", "mapk3 erk1", "erk1 downstream", "of met activated", "met activated ras", "activated ras may", "ras may require", "may require met", "require met endocytosis", "met endocytosis and", "endocytosis and signaling", "and signaling from", "signaling from endosomes", "endosomes peschard", "peschard et al.", "et al. 2001", "2001 hammond", "hammond et al.", "2001 petrelli", "petrelli et al.", "2002 kermorgant", "kermorgant and parker", "and parker 2008", "parker 2008 .
              binding", "2008 .
              binding of", ".
              binding of met", "of met to", "met to muc20", "to muc20 or", "muc20 or ranbp10", "or ranbp10 interferes", "ranbp10 interferes with", "interferes with ras", "with ras activation", "activation higuchi", "higuchi et al.", "2004 wang", "activated met receptor recruits", "met receptor recruits the", "receptor recruits the ras", "recruits the ras guanyl", "the ras guanyl nucleotide", "ras guanyl nucleotide exchange", "guanyl nucleotide exchange factor", "exchange factor gef", "gef sos1 indirectly", "sos1 indirectly either", "indirectly either through", "either through the grb2", "through the grb2 adapter", "grb2 adapter ponzetto", "adapter ponzetto et", "ponzetto et al. 1994", "al. 1994 fournier", "1994 fournier et", "fournier et al. 1996", "al. 1996 shen", "1996 shen and", "shen and novak 1997", "novak 1997 besser", "1997 besser et", "besser et al. 1997", "1997 gab1", "gab1 weidner et", "weidner et al. 1996", "al. 1996 or", "1996 or shc1", "or shc1 and grb2", "and grb2 pelicci", "grb2 pelicci et", "pelicci et al. 1995", "1995 or", "or ranbp9 wang", "ranbp9 wang et", "wang et al. 2002", "al. 2002 wang", "2002 wang et", "wang et al. 2004", "et al. 2004 .", "al. 2004 . association", "2004 . association of", ". association of sos1", "association of sos1 with", "of sos1 with the", "sos1 with the activated", "with the activated met", "the activated met receptor", "activated met receptor complex", "met receptor complex leads", "receptor complex leads to", "complex leads to exchange", "leads to exchange of", "to exchange of gdp", "exchange of gdp to", "of gdp to gtp", "gdp to gtp on", "to gtp on ras", "gtp on ras and", "on ras and activation", "ras and activation of", "and activation of ras", "activation of ras signaling", "ras signaling pelicci", "signaling pelicci et", "al. 1995 besser", "1995 besser et", "al. 1997 shen", "1997 shen and", "novak 1997 wang", "1997 wang et", "et al. 2004 .
              ptpn11", "2004 .
              ptpn11 shp2", "shp2 may contribute", "may contribute to activation", "contribute to activation of", "to activation of ras", "of ras signaling downstream", "ras signaling downstream of", "signaling downstream of met", "of met schaeper", "met schaeper et", "schaeper et al. 2000", "al. 2000 furcht", "2000 furcht et", "furcht et al. 2014", "et al. 2014 .
              sustained", "al. 2014 .
              sustained activation", "2014 .
              sustained activation of", ".
              sustained activation of mapk1", "of mapk1 erk2", "erk2 and mapk3", "and mapk3 erk1", "erk1 downstream of", "downstream of met activated", "of met activated ras", "met activated ras may", "activated ras may require", "ras may require met", "may require met endocytosis", "require met endocytosis and", "met endocytosis and signaling", "endocytosis and signaling from", "and signaling from endosomes", "from endosomes peschard", "endosomes peschard et", "peschard et al. 2001", "al. 2001 hammond", "2001 hammond et", "hammond et al. 2001", "al. 2001 petrelli", "2001 petrelli et", "petrelli et al. 2002", "al. 2002 kermorgant", "2002 kermorgant and", "kermorgant and parker 2008", "and parker 2008 .
              binding", "parker 2008 .
              binding of", "2008 .
              binding of met", ".
              binding of met to", "of met to muc20", "met to muc20 or", "to muc20 or ranbp10", "muc20 or ranbp10 interferes", "or ranbp10 interferes with", "ranbp10 interferes with ras", "interferes with ras activation", "ras activation higuchi", "activation higuchi et", "higuchi et al. 2004", "al. 2004 wang", "2004 wang et", "activated met receptor recruits the", "met receptor recruits the ras", "receptor recruits the ras guanyl", "recruits the ras guanyl nucleotide", "the ras guanyl nucleotide exchange", "ras guanyl nucleotide exchange factor", "nucleotide exchange factor gef", "factor gef sos1", "sos1 indirectly either through", "indirectly either through the", "either through the grb2 adapter", "the grb2 adapter ponzetto", "grb2 adapter ponzetto et", "adapter ponzetto et al.", "et al. 1994 fournier", "al. 1994 fournier et", "1994 fournier et al.", "et al. 1996 shen", "al. 1996 shen and", "1996 shen and novak", "and novak 1997 besser", "novak 1997 besser et", "1997 besser et al.", "al. 1997 gab1", "gab1 weidner et al.", "et al. 1996 or", "al. 1996 or shc1", "1996 or shc1 and", "shc1 and grb2 pelicci", "and grb2 pelicci et", "grb2 pelicci et al.", "al. 1995 or", "1995 or ranbp9", "or ranbp9 wang et", "ranbp9 wang et al.", "et al. 2002 wang", "al. 2002 wang et", "2002 wang et al.", "wang et al. 2004 .", "et al. 2004 . association", "al. 2004 . association of", "2004 . association of sos1", ". association of sos1 with", "association of sos1 with the", "of sos1 with the activated", "sos1 with the activated met", "with the activated met receptor", "the activated met receptor complex", "activated met receptor complex leads", "met receptor complex leads to", "receptor complex leads to exchange", "complex leads to exchange of", "leads to exchange of gdp", "to exchange of gdp to", "exchange of gdp to gtp", "of gdp to gtp on", "gdp to gtp on ras", "to gtp on ras and", "gtp on ras and activation", "on ras and activation of", "ras and activation of ras", "and activation of ras signaling", "of ras signaling pelicci", "ras signaling pelicci et", "signaling pelicci et al.", "et al. 1995 besser", "al. 1995 besser et", "1995 besser et al.", "et al. 1997 shen", "al. 1997 shen and", "1997 shen and novak", "and novak 1997 wang", "novak 1997 wang et", "1997 wang et al.", "wang et al. 2004 .
              ptpn11", "al. 2004 .
              ptpn11 shp2", ".
              ptpn11 shp2 may", "shp2 may contribute to", "may contribute to activation of", "contribute to activation of ras", "to activation of ras signaling", "activation of ras signaling downstream", "of ras signaling downstream of", "ras signaling downstream of met", "downstream of met schaeper", "of met schaeper et", "met schaeper et al.", "et al. 2000 furcht", "al. 2000 furcht et", "2000 furcht et al.", "furcht et al. 2014 .
              sustained", "et al. 2014 .
              sustained activation", "al. 2014 .
              sustained activation of", "2014 .
              sustained activation of mapk1", "activation of mapk1 erk2", "mapk1 erk2 and", "mapk3 erk1 downstream", "erk1 downstream of met", "downstream of met activated ras", "of met activated ras may", "met activated ras may require", "activated ras may require met", "ras may require met endocytosis", "may require met endocytosis and", "require met endocytosis and signaling", "met endocytosis and signaling from", "endocytosis and signaling from endosomes", "signaling from endosomes peschard", "from endosomes peschard et", "endosomes peschard et al.", "et al. 2001 hammond", "al. 2001 hammond et", "2001 hammond et al.", "et al. 2001 petrelli", "al. 2001 petrelli et", "2001 petrelli et al.", "et al. 2002 kermorgant", "al. 2002 kermorgant and", "2002 kermorgant and parker", "kermorgant and parker 2008 .
              binding", "and parker 2008 .
              binding of", "parker 2008 .
              binding of met", "2008 .
              binding of met to", ".
              binding of met to muc20", "of met to muc20 or", "met to muc20 or ranbp10", "to muc20 or ranbp10 interferes", "muc20 or ranbp10 interferes with", "or ranbp10 interferes with ras", "ranbp10 interferes with ras activation", "with ras activation higuchi", "ras activation higuchi et", "activation higuchi et al.", "et al. 2004 wang", "al. 2004 wang et", "2004 wang et al." ] }, { "record_id": "GLY_000594_1_1140", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8852405", "r hsa", "hsa 8852405", "r hsa 8852405" ] }, { "record_id": "GLY_000594_1_1140", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by mst1", "signaling by mst1", "inflammatory mediators", "mediators such", "such as", "as growth", "growth factors", "factors produced", "produced by", "by macrophages", "macrophages play", "play an", "an important", "important role", "role in", "in the", "the inflammatory", "inflammatory response", "response occurring", "occurring during", "during bacterial", "bacterial infection", "tissue injury", "injury and", "and immune", "immune responses.", "responses. many", "many growth", "factors and", "and their", "their receptor", "receptor type", "type protein", "protein tyrosine", "tyrosine kinases", "play a", "a critical", "critical role", "in inflammation", "wound healing", "healing and", "and tissue", "tissue remodelling.", "remodelling. the", "the growth", "growth factor", "factor hepatocyte", "hepatocyte growth", "factor like", "like protein", "also known", "known as", "as macrophage", "macrophage stimulating", "stimulating protein", "binds to", "to a", "a specific", "specific receptor", "protein receptor", "as ron", "recepteur d'origine", "d'origine nantais", "nantais .", ". mst1", "mst1 belongs", "belongs to", "to the", "the kringle", "kringle protein", "protein family", "which includes", "includes hgf", "hgf and", "and plasminogen.", "plasminogen. it", "it is", "is produced", "by the", "the liver", "liver and", "and circulates", "circulates in", "the blood", "blood as", "as a", "a biologically", "biologically inactive", "inactive single", "single chain", "chain precursor", "pro mst1", "mst1 .", ". proteolytic", "proteolytic cleavage", "cleavage of", "of pro", "mst1 into", "into the", "the biologically", "biologically active", "active mst1", "mst1 dimer", "dimer is", "is necessary", "necessary for", "for receptor", "receptor binding.", "binding. cleavage", "cleavage occurs", "occurs during", "during blood", "blood coagulation", "coagulation and", "and at", "at inflammatory", "inflammatory sites", "the resultant", "resultant mst1", "dimer then", "then binds", "binds mst1r", "mst1r receptors", "receptors on", "on local", "local macrophages.", "macrophages. mst1r", "mst1r is", "is ubiquitously", "ubiquitously expressed", "expressed but", "but mainly", "mainly in", "in epithelial", "epithelial cells.

              mst1", "cells.

              mst1 binding", "binding to", "to mst1r", "mst1r promotes", "promotes receptor", "receptor homodimerisation", "homodimerisation which", "which in", "in turn", "turn allows", "allows autophosphorylation", "autophosphorylation of", "of two", "two tyrosine", "tyrosine residues", "residues within", "within the", "the catalytic", "catalytic site", "site which", "which regulates", "regulates kinase", "kinase activity", "activity and", "and allows", "allows phosphorylation", "phosphorylation of", "of the", "the carboxy", "carboxy terminal", "terminal binding", "binding site", "site of", "the receptor.", "receptor. the", "the docking", "docking site", "site is", "is essential", "essential for", "for downstream", "downstream signaling", "signaling through", "through direct", "direct and", "and indirect", "indirect binding", "binding of", "of sh2", "sh2 domain", "domain containing", "containing adaptor", "adaptor proteins", "proteins such", "as grb2", "and src.", "src. mst1/mst1r", "mst1/mst1r signaling", "signaling plays", "plays a", "a dual", "dual role", "in regulating", "regulating inflammation", "initially stimulating", "stimulating chemotaxis", "chemotaxis and", "and phagocytosis", "macrophage activation", "and then", "then exerts", "exerts broad", "broad inhibitory", "inhibitory effects", "effects on", "on macrophages", "limiting the", "the extent", "extent of", "of inflammtory", "inflammtory responses", "wang et", "et al.", "al. 2002", "2002 .", ". mst1r", "is upregulated", "upregulated in", "in many", "many epithelial", "epithelial cancers", "cancers where", "where it", "is thought", "thought to", "to play", "a role", "the progression", "progression of", "of these", "these types", "types of", "of cancer", "kretschmann et", "al. 2010", "2010 .", "inflammatory mediators such", "mediators such as", "such as growth", "as growth factors", "growth factors produced", "factors produced by", "produced by macrophages", "by macrophages play", "macrophages play an", "play an important", "an important role", "important role in", "role in the", "in the inflammatory", "the inflammatory response", "inflammatory response occurring", "response occurring during", "occurring during bacterial", "during bacterial infection", "infection tissue", "tissue injury and", "injury and immune", "and immune responses.", "immune responses. many", "responses. many growth", "many growth factors", "growth factors and", "factors and their", "and their receptor", "their receptor type", "receptor type protein", "type protein tyrosine", "protein tyrosine kinases", "kinases rtks", "rtks play", "play a critical", "a critical role", "critical role in", "role in inflammation", "inflammation wound", "wound healing and", "healing and tissue", "and tissue remodelling.", "tissue remodelling. the", "remodelling. the growth", "the growth factor", "growth factor hepatocyte", "factor hepatocyte growth", "hepatocyte growth factor", "growth factor like", "factor like protein", "protein mst1", "mst1 also", "also known as", "known as macrophage", "as macrophage stimulating", "macrophage stimulating protein", "protein msp", "msp binds", "binds to a", "to a specific", "a specific receptor", "receptor macrophage", "stimulating protein receptor", "receptor mst1r", "mst1r also", "known as ron", "ron recepteur", "recepteur d'origine nantais", "d'origine nantais .", "nantais . mst1", ". mst1 belongs", "mst1 belongs to", "belongs to the", "to the kringle", "the kringle protein", "kringle protein family", "family which", "which includes hgf", "includes hgf and", "hgf and plasminogen.", "and plasminogen. it", "plasminogen. it is", "it is produced", "is produced by", "produced by the", "by the liver", "the liver and", "liver and circulates", "and circulates in", "circulates in the", "in the blood", "the blood as", "blood as a", "as a biologically", "a biologically inactive", "biologically inactive single", "inactive single chain", "single chain precursor", "precursor pro", "pro mst1 .", "mst1 . proteolytic", ". proteolytic cleavage", "proteolytic cleavage of", "cleavage of pro", "of pro mst1", "pro mst1 into", "mst1 into the", "into the biologically", "the biologically active", "biologically active mst1", "active mst1 dimer", "mst1 dimer is", "dimer is necessary", "is necessary for", "necessary for receptor", "for receptor binding.", "receptor binding. cleavage", "binding. cleavage occurs", "cleavage occurs during", "occurs during blood", "during blood coagulation", "blood coagulation and", "coagulation and at", "and at inflammatory", "at inflammatory sites", "sites the", "the resultant mst1", "resultant mst1 dimer", "mst1 dimer then", "dimer then binds", "then binds mst1r", "binds mst1r receptors", "mst1r receptors on", "receptors on local", "on local macrophages.", "local macrophages. mst1r", "macrophages. mst1r is", "mst1r is ubiquitously", "is ubiquitously expressed", "ubiquitously expressed but", "expressed but mainly", "but mainly in", "mainly in epithelial", "in epithelial cells.

              mst1", "epithelial cells.

              mst1 binding", "cells.

              mst1 binding to", "binding to mst1r", "to mst1r promotes", "mst1r promotes receptor", "promotes receptor homodimerisation", "receptor homodimerisation which", "homodimerisation which in", "which in turn", "in turn allows", "turn allows autophosphorylation", "allows autophosphorylation of", "autophosphorylation of two", "of two tyrosine", "two tyrosine residues", "tyrosine residues within", "residues within the", "within the catalytic", "the catalytic site", "catalytic site which", "site which regulates", "which regulates kinase", "regulates kinase activity", "kinase activity and", "activity and allows", "and allows phosphorylation", "allows phosphorylation of", "phosphorylation of the", "of the carboxy", "the carboxy terminal", "carboxy terminal binding", "terminal binding site", "binding site of", "site of the", "of the receptor.", "the receptor. the", "receptor. the docking", "the docking site", "docking site is", "site is essential", "is essential for", "essential for downstream", "for downstream signaling", "downstream signaling through", "signaling through direct", "through direct and", "direct and indirect", "and indirect binding", "indirect binding of", "binding of sh2", "of sh2 domain", "sh2 domain containing", "domain containing adaptor", "containing adaptor proteins", "adaptor proteins such", "proteins such as", "such as grb2", "grb2 pi3k", "pi3k and", "and src. mst1/mst1r", "src. mst1/mst1r signaling", "mst1/mst1r signaling plays", "signaling plays a", "plays a dual", "a dual role", "dual role in", "role in regulating", "in regulating inflammation", "inflammation initially", "initially stimulating chemotaxis", "stimulating chemotaxis and", "chemotaxis and phagocytosis", "phagocytosis macrophage", "activation and", "and then exerts", "then exerts broad", "exerts broad inhibitory", "broad inhibitory effects", "inhibitory effects on", "effects on macrophages", "macrophages limiting", "limiting the extent", "the extent of", "extent of inflammtory", "of inflammtory responses", "responses wang", "wang et al.", "et al. 2002", "al. 2002 .", "2002 . mst1r", ". mst1r is", "mst1r is upregulated", "is upregulated in", "upregulated in many", "in many epithelial", "many epithelial cancers", "epithelial cancers where", "cancers where it", "where it is", "it is thought", "is thought to", "thought to play", "to play a", "play a role", "a role in", "in the progression", "the progression of", "progression of these", "of these types", "these types of", "types of cancer", "cancer kretschmann", "kretschmann et al.", "et al. 2010", "al. 2010 .", "inflammatory mediators such as", "mediators such as growth", "such as growth factors", "as growth factors produced", "growth factors produced by", "factors produced by macrophages", "produced by macrophages play", "by macrophages play an", "macrophages play an important", "play an important role", "an important role in", "important role in the", "role in the inflammatory", "in the inflammatory response", "the inflammatory response occurring", "inflammatory response occurring during", "response occurring during bacterial", "occurring during bacterial infection", "bacterial infection tissue", "infection tissue injury", "tissue injury and immune", "injury and immune responses.", "and immune responses. many", "immune responses. many growth", "responses. many growth factors", "many growth factors and", "growth factors and their", "factors and their receptor", "and their receptor type", "their receptor type protein", "receptor type protein tyrosine", "type protein tyrosine kinases", "tyrosine kinases rtks", "rtks play a", "play a critical role", "a critical role in", "critical role in inflammation", "in inflammation wound", "inflammation wound healing", "wound healing and tissue", "healing and tissue remodelling.", "and tissue remodelling. the", "tissue remodelling. the growth", "remodelling. the growth factor", "the growth factor hepatocyte", "growth factor hepatocyte growth", "factor hepatocyte growth factor", "hepatocyte growth factor like", "growth factor like protein", "like protein mst1", "mst1 also known", "also known as macrophage", "known as macrophage stimulating", "as macrophage stimulating protein", "stimulating protein msp", "msp binds to", "binds to a specific", "to a specific receptor", "specific receptor macrophage", "receptor macrophage stimulating", "macrophage stimulating protein receptor", "protein receptor mst1r", "mst1r also known", "also known as ron", "as ron recepteur", "ron recepteur d'origine", "recepteur d'origine nantais .", "d'origine nantais . mst1", "nantais . mst1 belongs", ". mst1 belongs to", "mst1 belongs to the", "belongs to the kringle", "to the kringle protein", "the kringle protein family", "protein family which", "family which includes", "which includes hgf and", "includes hgf and plasminogen.", "hgf and plasminogen. it", "and plasminogen. it is", "plasminogen. it is produced", "it is produced by", "is produced by the", "produced by the liver", "by the liver and", "the liver and circulates", "liver and circulates in", "and circulates in the", "circulates in the blood", "in the blood as", "the blood as a", "blood as a biologically", "as a biologically inactive", "a biologically inactive single", "biologically inactive single chain", "inactive single chain precursor", "chain precursor pro", "precursor pro mst1", "pro mst1 . proteolytic", "mst1 . proteolytic cleavage", ". proteolytic cleavage of", "proteolytic cleavage of pro", "cleavage of pro mst1", "of pro mst1 into", "pro mst1 into the", "mst1 into the biologically", "into the biologically active", "the biologically active mst1", "biologically active mst1 dimer", "active mst1 dimer is", "mst1 dimer is necessary", "dimer is necessary for", "is necessary for receptor", "necessary for receptor binding.", "for receptor binding. cleavage", "receptor binding. cleavage occurs", "binding. cleavage occurs during", "cleavage occurs during blood", "occurs during blood coagulation", "during blood coagulation and", "blood coagulation and at", "coagulation and at inflammatory", "and at inflammatory sites", "inflammatory sites the", "sites the resultant", "the resultant mst1 dimer", "resultant mst1 dimer then", "mst1 dimer then binds", "dimer then binds mst1r", "then binds mst1r receptors", "binds mst1r receptors on", "mst1r receptors on local", "receptors on local macrophages.", "on local macrophages. mst1r", "local macrophages. mst1r is", "macrophages. mst1r is ubiquitously", "mst1r is ubiquitously expressed", "is ubiquitously expressed but", "ubiquitously expressed but mainly", "expressed but mainly in", "but mainly in epithelial", "mainly in epithelial cells.

              mst1", "in epithelial cells.

              mst1 binding", "epithelial cells.

              mst1 binding to", "cells.

              mst1 binding to mst1r", "binding to mst1r promotes", "to mst1r promotes receptor", "mst1r promotes receptor homodimerisation", "promotes receptor homodimerisation which", "receptor homodimerisation which in", "homodimerisation which in turn", "which in turn allows", "in turn allows autophosphorylation", "turn allows autophosphorylation of", "allows autophosphorylation of two", "autophosphorylation of two tyrosine", "of two tyrosine residues", "two tyrosine residues within", "tyrosine residues within the", "residues within the catalytic", "within the catalytic site", "the catalytic site which", "catalytic site which regulates", "site which regulates kinase", "which regulates kinase activity", "regulates kinase activity and", "kinase activity and allows", "activity and allows phosphorylation", "and allows phosphorylation of", "allows phosphorylation of the", "phosphorylation of the carboxy", "of the carboxy terminal", "the carboxy terminal binding", "carboxy terminal binding site", "terminal binding site of", "binding site of the", "site of the receptor.", "of the receptor. the", "the receptor. the docking", "receptor. the docking site", "the docking site is", "docking site is essential", "site is essential for", "is essential for downstream", "essential for downstream signaling", "for downstream signaling through", "downstream signaling through direct", "signaling through direct and", "through direct and indirect", "direct and indirect binding", "and indirect binding of", "indirect binding of sh2", "binding of sh2 domain", "of sh2 domain containing", "sh2 domain containing adaptor", "domain containing adaptor proteins", "containing adaptor proteins such", "adaptor proteins such as", "proteins such as grb2", "as grb2 pi3k", "pi3k and src.", "and src. mst1/mst1r signaling", "src. mst1/mst1r signaling plays", "mst1/mst1r signaling plays a", "signaling plays a dual", "plays a dual role", "a dual role in", "dual role in regulating", "role in regulating inflammation", "regulating inflammation initially", "inflammation initially stimulating", "initially stimulating chemotaxis and", "stimulating chemotaxis and phagocytosis", "and phagocytosis macrophage", "phagocytosis macrophage activation", "macrophage activation and", "activation and then", "and then exerts broad", "then exerts broad inhibitory", "exerts broad inhibitory effects", "broad inhibitory effects on", "inhibitory effects on macrophages", "on macrophages limiting", "macrophages limiting the", "limiting the extent of", "the extent of inflammtory", "extent of inflammtory responses", "inflammtory responses wang", "responses wang et", "wang et al. 2002", "et al. 2002 .", "al. 2002 . mst1r", "2002 . mst1r is", ". mst1r is upregulated", "mst1r is upregulated in", "is upregulated in many", "upregulated in many epithelial", "in many epithelial cancers", "many epithelial cancers where", "epithelial cancers where it", "cancers where it is", "where it is thought", "it is thought to", "is thought to play", "thought to play a", "to play a role", "play a role in", "a role in the", "role in the progression", "in the progression of", "the progression of these", "progression of these types", "of these types of", "these types of cancer", "of cancer kretschmann", "cancer kretschmann et", "kretschmann et al. 2010", "et al. 2010 .", "inflammatory mediators such as growth", "mediators such as growth factors", "such as growth factors produced", "as growth factors produced by", "growth factors produced by macrophages", "factors produced by macrophages play", "produced by macrophages play an", "by macrophages play an important", "macrophages play an important role", "play an important role in", "an important role in the", "important role in the inflammatory", "role in the inflammatory response", "in the inflammatory response occurring", "the inflammatory response occurring during", "inflammatory response occurring during bacterial", "response occurring during bacterial infection", "during bacterial infection tissue", "bacterial infection tissue injury", "infection tissue injury and", "tissue injury and immune responses.", "injury and immune responses. many", "and immune responses. many growth", "immune responses. many growth factors", "responses. many growth factors and", "many growth factors and their", "growth factors and their receptor", "factors and their receptor type", "and their receptor type protein", "their receptor type protein tyrosine", "receptor type protein tyrosine kinases", "protein tyrosine kinases rtks", "kinases rtks play", "rtks play a critical", "play a critical role in", "a critical role in inflammation", "role in inflammation wound", "in inflammation wound healing", "inflammation wound healing and", "wound healing and tissue remodelling.", "healing and tissue remodelling. the", "and tissue remodelling. the growth", "tissue remodelling. the growth factor", "remodelling. the growth factor hepatocyte", "the growth factor hepatocyte growth", "growth factor hepatocyte growth factor", "factor hepatocyte growth factor like", "hepatocyte growth factor like protein", "factor like protein mst1", "protein mst1 also", "mst1 also known as", "also known as macrophage stimulating", "known as macrophage stimulating protein", "macrophage stimulating protein msp", "protein msp binds", "msp binds to a", "binds to a specific receptor", "a specific receptor macrophage", "specific receptor macrophage stimulating", "receptor macrophage stimulating protein", "stimulating protein receptor mst1r", "receptor mst1r also", "mst1r also known as", "known as ron recepteur", "as ron recepteur d'origine", "ron recepteur d'origine nantais", "recepteur d'origine nantais . mst1", "d'origine nantais . mst1 belongs", "nantais . mst1 belongs to", ". mst1 belongs to the", "mst1 belongs to the kringle", "belongs to the kringle protein", "to the kringle protein family", "kringle protein family which", "protein family which includes", "family which includes hgf", "which includes hgf and plasminogen.", "includes hgf and plasminogen. it", "hgf and plasminogen. it is", "and plasminogen. it is produced", "plasminogen. it is produced by", "it is produced by the", "is produced by the liver", "produced by the liver and", "by the liver and circulates", "the liver and circulates in", "liver and circulates in the", "and circulates in the blood", "circulates in the blood as", "in the blood as a", "the blood as a biologically", "blood as a biologically inactive", "as a biologically inactive single", "a biologically inactive single chain", "biologically inactive single chain precursor", "single chain precursor pro", "chain precursor pro mst1", "precursor pro mst1 .", "pro mst1 . proteolytic cleavage", "mst1 . proteolytic cleavage of", ". proteolytic cleavage of pro", "proteolytic cleavage of pro mst1", "cleavage of pro mst1 into", "of pro mst1 into the", "pro mst1 into the biologically", "mst1 into the biologically active", "into the biologically active mst1", "the biologically active mst1 dimer", "biologically active mst1 dimer is", "active mst1 dimer is necessary", "mst1 dimer is necessary for", "dimer is necessary for receptor", "is necessary for receptor binding.", "necessary for receptor binding. cleavage", "for receptor binding. cleavage occurs", "receptor binding. cleavage occurs during", "binding. cleavage occurs during blood", "cleavage occurs during blood coagulation", "occurs during blood coagulation and", "during blood coagulation and at", "blood coagulation and at inflammatory", "coagulation and at inflammatory sites", "at inflammatory sites the", "inflammatory sites the resultant", "sites the resultant mst1", "the resultant mst1 dimer then", "resultant mst1 dimer then binds", "mst1 dimer then binds mst1r", "dimer then binds mst1r receptors", "then binds mst1r receptors on", "binds mst1r receptors on local", "mst1r receptors on local macrophages.", "receptors on local macrophages. mst1r", "on local macrophages. mst1r is", "local macrophages. mst1r is ubiquitously", "macrophages. mst1r is ubiquitously expressed", "mst1r is ubiquitously expressed but", "is ubiquitously expressed but mainly", "ubiquitously expressed but mainly in", "expressed but mainly in epithelial", "but mainly in epithelial cells.

              mst1", "mainly in epithelial cells.

              mst1 binding", "in epithelial cells.

              mst1 binding to", "epithelial cells.

              mst1 binding to mst1r", "cells.

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many", "as many as", "many as 70", "as 70 rabs", "70 rabs and", "rabs and at", "and at least", "at least 51", "least 51 putative", "51 putative rab", "putative rab gaps", "gaps pfeffer", "pfeffer 2005 .", "2005 . only", ". only a", "only a few", "a few of", "few of these", "of these gaps", "these gaps have", "gaps have been", "have been matched", "been matched to", "matched to a", "to a specific", "a specific rab", "specific rab substrate.", "rab substrate. the", "substrate. the tre", "the tre 2/bub2/cdc16", "2/bub2/cdc16 tbc", "domain containing rab", "containing rab specific", "rab specific gaps", "gaps tbc/rabgaps", "are a key", "a key family", "key family of", "family of rab", "of rab regulators", "regulators where", "where the tbc", "the tbc domain", "tbc domain facilitates", "domain facilitates the", "facilitates the inactivation", "of rabs by", "rabs by facilitating", "by facilitating activation", "facilitating activation of", "activation of gtpase", "of gtpase activity", "rab pan", "pan et al.", "et al. 2006", "2006 frasa", "frasa et al.", "et al. 2012", "2012 stenmark", "stenmark 2009 .", "2009 . studies", ". studies suggest", "studies suggest that", "suggest that tbc/rabgaps", "that tbc/rabgaps are", "tbc/rabgaps are more", "are more than", "more than just", "than just negative", "just negative regulators", "negative regulators of", "regulators of rabs", "of rabs and", "rabs and can", "and can integrate", "can integrate signalling", "integrate signalling between", "signalling between rabs", "between rabs and", "rabs and other", "and other small", "other small gtpases", "gtpases thereby", "thereby regulating numerous", "regulating numerous cellular", "numerous cellular processes", "cellular processes like", "processes like intracellular", "like intracellular trafficking", "trafficking frasa", "al. 2012 .", "rab gtpases are peripheral", "gtpases are peripheral membrane", "are peripheral membrane proteins", "peripheral membrane proteins involved", "membrane 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2001 stenmark", "2001 stenmark 2009", "stenmark 2009 zhen", "2009 zhen &", "zhen & stenmark 2015", "stenmark 2015 cherfils", "2015 cherfils &", "cherfils & zeghouf 2013", "& zeghouf 2013 .", "zeghouf 2013 . conversion", "2013 . conversion from", ". conversion from the", "conversion from the gtp", "the gtp to", "gtp to the", "to the gdp bound", "the gdp bound form", "gdp bound form occurs", "bound form occurs through", "form occurs through gtp", "occurs through gtp hydrolysis", "gtp hydrolysis which", "hydrolysis which is", "which is not only", "is not only driven", "not only driven by", "only driven by the", "driven by the intrinsic", "by the intrinsic gtpase", "the intrinsic gtpase activity", "intrinsic gtpase activity of", "gtpase activity of the", "activity of the rab", "of the rab protein", "the rab protein but", "rab protein but is", "protein but is also", "but is also catalysed", "is also catalysed by", "also catalysed by gtpase", "catalysed by gtpase activating", "by gtpase 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"2015 cherfils & zeghouf", "cherfils & zeghouf 2013 .", "& zeghouf 2013 . conversion", "zeghouf 2013 . conversion from", "2013 . conversion from the", ". conversion from the gtp", "from the gtp to", "the gtp to the", "gtp to the gdp", "to the gdp bound form", "the gdp bound form occurs", "gdp bound form occurs through", "bound form occurs through gtp", "form occurs through gtp hydrolysis", "through gtp hydrolysis which", "gtp hydrolysis which is", "hydrolysis which is not", "which is not only driven", "is not only driven by", "not only driven by the", "only driven by the intrinsic", "driven by the intrinsic gtpase", "by the intrinsic gtpase activity", "the intrinsic gtpase activity of", "intrinsic gtpase activity of the", "gtpase activity of the rab", "activity of the rab protein", "of the rab protein but", "the rab protein but is", "rab protein but is also", "protein but is also catalysed", "but is also catalysed by", "is also catalysed by gtpase", "also catalysed by gtpase 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et al. 2016", "al. 2016 longsdon", "2016 longsdon et", "longsdon et al. 2012", "et al. 2012 .", "the interleukin 20 il20", "20 il20 subfamily", "il20 subfamily comprises il19", "subfamily comprises il19 il20", "il19 il20 il22", "il20 il22 il24", "il22 il24 and il26.", "il24 and il26. they are", "and il26. they are members", "il26. they are members of", "they are members of the", "are members of the larger", "members of the larger il10", "of the larger il10 family", "larger il10 family but", "il10 family but have", "family but have been", "but have been grouped together", "have been grouped together based", "been grouped together based on", "grouped together based on their", "together based on their usage", "based on their usage of", "on their usage of common", "their usage of common receptor", "usage of common receptor subunits", "of common receptor subunits and", "common receptor subunits and similarities", "receptor subunits and similarities in", "subunits and similarities in their", "and similarities in their target", "similarities in their target cell", "in their target cell profiles", "their target cell profiles and", "target cell profiles and biological", "cell profiles and biological functions.", "profiles and biological functions. members", "and biological functions. members of", "biological functions. members of the", "functions. members of the il20", "members of the il20 subfamily", "of the il20 subfamily facilitate", "the il20 subfamily facilitate the", "il20 subfamily facilitate the communication", "subfamily facilitate the communication between", "facilitate the communication between leukocytes", "the communication between leukocytes and", "communication between leukocytes and epithelial", "between leukocytes and epithelial cells", "and epithelial cells thereby", "epithelial cells thereby enhancing", "cells thereby enhancing innate", "thereby enhancing innate defence mechanisms", "enhancing innate defence mechanisms and", "innate defence mechanisms and tissue", "defence mechanisms and tissue repair", "mechanisms and tissue repair processes", "and tissue repair processes at", "tissue repair processes at epithelial", "repair processes at epithelial surfaces.", "processes at epithelial surfaces. much", "at epithelial surfaces. much of", "epithelial surfaces. much of the", "surfaces. much of the understanding", "much of the understanding of", "of the understanding of this", "the understanding of this group", "understanding of this group of", "of this group of cytokines", "this group of cytokines is", "group of cytokines is based", "of cytokines is based on", "cytokines is based on il22", "based on il22 which", "on il22 which is", "il22 which is the", "which is the most studied", "is the most studied member", "most studied member rutz", "studied member rutz et", "member rutz et al.", "et al. 2014 akdis", "al. 2014 akdis m", "2014 akdis m et", "akdis m et al. 2016", "et al. 2016 longsdon", "al. 2016 longsdon et", "2016 longsdon et al.", 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. p25", ". p25 has", "p25 has a", "has a six", "a six fold", "six fold longer", "fold longer half", "longer half life", "half life compared", "life compared to", "compared to p35", "to p35 and", "p35 and lacks", "and lacks the", "lacks the membrane", "the membrane anchoring", "membrane anchoring signal", "signal which", "which results in", "results in its", "in its constitutive", "its constitutive activation", "constitutive activation and", "activation and mislocalization", "and mislocalization of", "mislocalization of the", "of the cdk5:p25", "the cdk5:p25 complex", "cdk5:p25 complex to", "complex to the", "to the cytoplasm", "the cytoplasm and", "cytoplasm and the", "and the nucleus.", "the nucleus. there", "there cdk5:p25", "cdk5:p25 is able", "is able to", "able to access", "to access and", "access and phosphorylate", "and phosphorylate a", "phosphorylate a variety", "variety of atypical", "of atypical targets", "targets triggering", "triggering a cascade", "a cascade of", "cascade 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kinases causing", "kinases causing neuronal", "causing neuronal death.", "neuronal death. consistent", "death. consistent with", "consistent with this", "with this mechanism", "mechanism higher", "and cdc25c activities", "cdc25c activities were", "activities were observed", "were observed in", "observed in human", "in human alzheimer's", "human alzheimer's disease", "disease ad", "ad clinical", "samples as", "as compared to", "compared to age", "to age matched", "age matched controls.", "matched controls. inhibition", "controls. inhibition of", "inhibition of cdc25", "of cdc25 isoforms", "cdc25 isoforms confers", "isoforms confers neuroprotection", "confers neuroprotection to", "neuroprotection to beta", "to beta amyloid", "beta amyloid toxicity", "toxicity which", "which underscores the", "underscores the contribution", "the contribution of", "contribution of this", "of this pathway", "this pathway to", "pathway to ad", "to ad pathogenesis", "post mitotic neurons do", "mitotic neurons 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has", "cycle proteins has been", "proteins has been shown", "has been shown to", "been shown to play", "shown to play a", "to play a key", "play a key role", "a key role in", "key role in the", "role in the pathogenesis", "in the pathogenesis of", "the pathogenesis of several", "pathogenesis of several neurodegenerative", "of several neurodegenerative disorders", "neurodegenerative disorders yang", "disorders yang et", "yang et al. 2003", "al. 2003 lopes", "2003 lopes et", "lopes et al. 2009", "et al. 2009 .", "al. 2009 . cdk5", "2009 . cdk5 is", ". cdk5 is not", "cdk5 is not activated", "is not activated by", "not activated by the", "activated by the canonical", "by the canonical cyclins", "canonical cyclins but", "cyclins but binds", "but binds to its", "binds to its own", "to its own specific", "its own specific partners", "specific partners cdk5r1", "partners cdk5r1 and", "and cdk5r2 aka", "cdk5r2 aka p35", "aka p35 and p39", "and p39 respectively", "respectively tsai", "tsai et al. 1994", "al. 1994 tang", "1994 tang et", "tang et al. 1995", "et al. 1995 .", "al. 1995 . expression", "1995 . expression of", ". expression of p35", "expression of p35 is", "of p35 is nearly", "p35 is nearly ubiquitous", "nearly ubiquitous whereas", "ubiquitous whereas p39", "whereas p39 is largely", "p39 is largely expressed", "is largely expressed in", "largely expressed in the", "expressed in the central", "in the central nervous", "the central nervous system.", "central nervous system. a", "nervous system. a variety", "system. a variety of", "a variety of neurotoxic", "variety of neurotoxic insults", "of neurotoxic insults such", "neurotoxic insults such as", "insults such as beta", "such as beta amyloid", "beta amyloid a", "amyloid a beta", "beta ischemia", "ischemia excitotoxicity and", "excitotoxicity and oxidative stress", "and oxidative stress disrupt", "oxidative stress disrupt the", "stress disrupt the intracellular", "disrupt the intracellular calcium", "the intracellular calcium homeostasis", "intracellular calcium homeostasis in", "calcium homeostasis in neurons", "in neurons thereby", "neurons thereby leading", "thereby leading to the", "leading to the activation", "to the activation of", "the activation of calpain", "of calpain which", "calpain which cleaves", "which cleaves p35 into", "cleaves p35 into p25", "p35 into p25 and", "into p25 and p10", "and p10 lee", "p10 lee et", "lee et al. 2000", "et al. 2000 .", "al. 2000 . p25", "2000 . p25 has", ". p25 has a", "p25 has a six", "has a six fold", "a six fold longer", "six fold longer half", "fold longer half life", "longer half life compared", "half life compared to", "life compared to p35", "compared to p35 and", "to p35 and lacks", "p35 and lacks the", "and lacks the membrane", "lacks the membrane anchoring", "the membrane anchoring signal", "anchoring signal which", "signal which results", "which results in its", "results in its constitutive", "in its constitutive activation", "its 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neuronal death. one", "neuronal death. one such", "death. one such neurotoxic", "one such neurotoxic pathway", "such neurotoxic pathway involves", "neurotoxic pathway involves cdk5", "pathway involves cdk5 mediated", "involves cdk5 mediated random", "cdk5 mediated random activation", "mediated random activation of", "cell cycle proteins which", "cycle proteins which culminate", "proteins which culminate in", "which culminate in neuronal", "in neuronal death. exposure", "neuronal death. exposure of", "death. exposure of primary", "exposure of primary cortical", "of primary cortical neurons", "primary cortical neurons to", "cortical neurons to oligomeric", "neurons to oligomeric beta", "to oligomeric beta amyloid", "beta amyloid 1", "amyloid 1 42", "1 42 hyper", "42 hyper activates", "hyper activates cdk5 due", "activates cdk5 due to", "cdk5 due to p25", "due to p25 formation", "p25 formation which", "formation which in", "which in turn phosphorylates", "in turn phosphorylates cdc25a", "phosphorylates cdc25a cdc25b", "cdc25a cdc25b and", "cdc25b and cdc25c. cdk5", "and cdc25c. cdk5 phosphorylates", "cdc25c. cdk5 phosphorylates cdc25a", "cdk5 phosphorylates cdc25a at", "phosphorylates cdc25a at s40", "at s40 s116", "s40 s116 and", "and s261 cdc25b", "s261 cdc25b at", "at s50 t69", "s160 s321 and", "and s470 and", "s470 and cdc25c", "and cdc25c at t48", "at t48 t67", "t130 s168 and", "s168 and s214. cdk5", "and s214. cdk5 mediated", "s214. cdk5 mediated phosphorylation", "cdk5 mediated phosphorylation of", "mediated phosphorylation of cdc25a", "of cdc25a cdc25b", "cdc25b and cdc25c not", "and cdc25c not only", "cdc25c not only increases", "not only increases their", "only increases their phosphatase", "increases their phosphatase activities", "their phosphatase activities but", "phosphatase activities but also", "activities but also facilitates", "but also facilitates their", "also facilitates their release", "facilitates their release from", "their release from 14", "release from 14 3", "from 14 3 3", "14 3 3 inhibitory", "3 3 inhibitory binding.", "3 inhibitory binding. cdc25a", "binding. cdc25a cdc25b", "cdc25b and cdc25c in", "and cdc25c in turn", "cdc25c in turn activate", "in turn activate cdk1", "activate cdk1 cdk2", "cdk1 cdk2 and", "cdk2 and cdk4 kinases", "and cdk4 kinases causing", "cdk4 kinases causing neuronal", "kinases causing neuronal death.", "causing neuronal death. consistent", "neuronal death. consistent with", "death. consistent with this", "consistent with this mechanism", "this mechanism higher", "mechanism higher cdc25a", "higher cdc25a cdc25b", "cdc25b and cdc25c activities", "and cdc25c activities were", "cdc25c activities were observed", "activities were observed in", "were observed in human", "observed in human alzheimer's", "in human alzheimer's disease", "alzheimer's disease ad", "ad clinical samples", "clinical samples as", "samples as compared", "as compared to age", "compared to age matched", "to age matched controls.", "age matched controls. inhibition", "matched controls. inhibition of", "controls. inhibition of cdc25", "inhibition of cdc25 isoforms", "of cdc25 isoforms confers", "cdc25 isoforms confers neuroprotection", "isoforms confers neuroprotection to", "confers neuroprotection to beta", "neuroprotection to beta amyloid", "to beta amyloid toxicity", "amyloid toxicity which", "toxicity which underscores", "which underscores the contribution", "underscores the contribution of", "the contribution of this", "contribution of this pathway", "of this pathway to", "this pathway to ad", "pathway to ad pathogenesis", "post mitotic neurons do not", "mitotic neurons do not have", "neurons do not have an", "do not have an active", "not have an active cell", "have an active cell cycle.", "an active cell cycle. however", "cell cycle. however deregulation", "cycle. however deregulation of", "however deregulation of cyclin", "deregulation of cyclin dependent kinase", "of cyclin dependent kinase 5", "dependent kinase 5 cdk5", "5 cdk5 activity", "cdk5 activity in these", "activity in these neurons can", "in these neurons can aberrantly", "these neurons can aberrantly activate", "neurons can aberrantly activate various", "can aberrantly activate various components", "aberrantly activate various components of", "activate various components of cell", "various components of cell cycle", "components of cell cycle leading", "of cell cycle leading to", "cell cycle leading to neuronal", "cycle leading to neuronal death", "to neuronal death chang", "neuronal death chang et", "death chang et al.", "chang et al. 2012 .", "et al. 2012 . random", "al. 2012 . random activation", "2012 . random activation of", ". random activation of cell", "random activation of cell cycle", "activation of cell cycle proteins", "of cell cycle proteins has", "cell cycle proteins has been", "cycle proteins has been shown", "proteins has been shown to", "has been shown to play", "been shown to play a", "shown to play a key", "to play a key role", "play a key role in", "a key role in the", "key role in the pathogenesis", "role in the pathogenesis of", "in the pathogenesis of several", "the pathogenesis of several neurodegenerative", "pathogenesis of several neurodegenerative disorders", "several neurodegenerative disorders yang", "neurodegenerative disorders yang et", "disorders yang et al.", "et al. 2003 lopes", "al. 2003 lopes et", "2003 lopes et al.", "lopes et al. 2009 .", "et al. 2009 . cdk5", "al. 2009 . cdk5 is", "2009 . cdk5 is not", ". cdk5 is not activated", "cdk5 is not activated by", "is not activated by the", "not activated by the canonical", "activated by the canonical cyclins", "the canonical cyclins but", "canonical cyclins but binds", "cyclins but binds to", "but binds to its own", "binds to its own specific", "to its own specific partners", "own specific partners cdk5r1", "specific partners cdk5r1 and", "partners cdk5r1 and cdk5r2", "cdk5r1 and cdk5r2 aka", "and cdk5r2 aka p35", "cdk5r2 aka p35 and", "p35 and p39 respectively", "respectively tsai et", "et al. 1994 tang", "al. 1994 tang et", "1994 tang et al.", "tang et al. 1995 .", "et al. 1995 . expression", "al. 1995 . expression of", "1995 . expression of p35", ". expression of p35 is", "expression of p35 is nearly", "of p35 is nearly ubiquitous", "is nearly ubiquitous whereas", "nearly ubiquitous whereas p39", "ubiquitous whereas p39 is", "whereas p39 is largely expressed", "p39 is largely expressed in", "is largely expressed in the", "largely expressed in the central", "expressed in the central nervous", "in the central nervous system.", "the central nervous system. a", "central nervous system. a variety", "nervous system. a variety of", "system. a variety of neurotoxic", "a variety of neurotoxic insults", "variety of neurotoxic insults such", "of neurotoxic insults such as", "neurotoxic insults such as beta", "insults such as beta amyloid", "as beta amyloid a", "beta amyloid a beta", "a beta ischemia", "ischemia excitotoxicity and oxidative", "excitotoxicity and oxidative stress disrupt", "and oxidative stress disrupt the", "oxidative stress disrupt the intracellular", "stress disrupt the intracellular calcium", "disrupt the intracellular calcium homeostasis", "the intracellular calcium homeostasis in", "intracellular calcium homeostasis in neurons", "homeostasis in neurons thereby", "in neurons thereby leading", "neurons thereby leading to", "thereby leading to the activation", "leading to the activation of", "to the activation of calpain", "activation of calpain which", "of calpain which cleaves", "calpain which cleaves p35", "which cleaves p35 into p25", "cleaves p35 into p25 and", "p35 into p25 and p10", "p25 and p10 lee", "and p10 lee et", "p10 lee et al.", "lee et al. 2000 .", "et al. 2000 . p25", "al. 2000 . p25 has", "2000 . p25 has a", ". p25 has a six", "p25 has a six fold", "has a six fold longer", "a six fold longer half", "six fold longer half life", "fold longer half life compared", "longer half life compared to", "half life compared to p35", "life compared to p35 and", "compared to p35 and lacks", "to p35 and lacks the", "p35 and lacks the membrane", "and lacks the membrane anchoring", "lacks the membrane anchoring signal", "membrane anchoring signal which", "anchoring signal which results", "signal which results in", "which results in its constitutive", "results in its constitutive activation", "in its constitutive activation and", "its constitutive activation and mislocalization", "constitutive activation and mislocalization of", "activation and mislocalization of the", "and mislocalization of the cdk5:p25", "mislocalization of the cdk5:p25 complex", "of the cdk5:p25 complex to", "the cdk5:p25 complex to the", "cdk5:p25 complex to the cytoplasm", "complex to the cytoplasm and", "to the cytoplasm and the", "the cytoplasm and the nucleus.", "cytoplasm and the nucleus. there", "the nucleus. there cdk5:p25", "nucleus. there cdk5:p25 is", "there cdk5:p25 is able", "cdk5:p25 is able to access", "is able to access and", "able to access and phosphorylate", "to access and phosphorylate a", "access and phosphorylate a variety", "and phosphorylate a variety of", "phosphorylate a variety of atypical", "a variety of atypical targets", "of atypical targets triggering", "atypical targets triggering a", "targets triggering a cascade", "triggering a cascade of neurotoxic", "a cascade of neurotoxic pathways", "cascade of neurotoxic pathways that", "of neurotoxic pathways that culminate", "neurotoxic pathways that culminate in", "pathways that culminate in neuronal", "that culminate in neuronal death.", "culminate in neuronal death. one", "in neuronal death. one such", "neuronal death. one such neurotoxic", "death. one such neurotoxic pathway", "one such neurotoxic pathway involves", "such neurotoxic pathway involves cdk5", "neurotoxic pathway involves cdk5 mediated", "pathway involves cdk5 mediated random", "involves cdk5 mediated random activation", "cdk5 mediated random activation of", "mediated random activation of cell", "of cell cycle proteins which", "cell cycle proteins which culminate", "cycle proteins which culminate in", "proteins which culminate in neuronal", "which culminate in neuronal death.", "culminate in neuronal death. exposure", "in neuronal death. exposure of", "neuronal death. exposure of primary", "death. exposure of primary cortical", "exposure of primary cortical neurons", "of primary cortical neurons to", "primary cortical neurons to oligomeric", "cortical neurons to oligomeric beta", "neurons to oligomeric beta amyloid", "oligomeric beta amyloid 1", "beta amyloid 1 42", "1 42 hyper activates", "42 hyper activates cdk5", "hyper activates cdk5 due to", "activates cdk5 due to p25", "cdk5 due to p25 formation", "to p25 formation which", "p25 formation which in", "formation which in turn", "which in turn phosphorylates cdc25a", "turn phosphorylates cdc25a cdc25b", "phosphorylates cdc25a cdc25b and", "cdc25a cdc25b and cdc25c.", "cdc25b and cdc25c. cdk5 phosphorylates", "and cdc25c. cdk5 phosphorylates cdc25a", "cdc25c. cdk5 phosphorylates cdc25a at", "cdk5 phosphorylates cdc25a at s40", "cdc25a at s40 s116", "at s40 s116 and", "s40 s116 and s261", "s116 and s261 cdc25b", "and s261 cdc25b at", "s261 cdc25b at s50", "cdc25b at s50 t69", "s50 t69 s160", "t69 s160 s321", "s160 s321 and s470", "s321 and s470 and", "and s470 and cdc25c", "s470 and cdc25c at", "cdc25c at t48 t67", "t48 t67 s122", "t67 s122 t130", "s122 t130 s168", "t130 s168 and s214.", "s168 and s214. cdk5 mediated", "and s214. cdk5 mediated phosphorylation", "s214. cdk5 mediated phosphorylation of", "cdk5 mediated phosphorylation of cdc25a", "phosphorylation of cdc25a cdc25b", "of cdc25a cdc25b and", "cdc25a cdc25b and cdc25c", "cdc25b and cdc25c not only", "and cdc25c not only increases", "cdc25c not only increases their", "not only increases their phosphatase", "only increases their phosphatase activities", "increases their phosphatase activities but", "their phosphatase activities but also", "phosphatase activities but also facilitates", "activities but also facilitates their", "but also facilitates their release", "also facilitates their release from", "facilitates their release from 14", "their release from 14 3", "release from 14 3 3", "from 14 3 3 inhibitory", "14 3 3 inhibitory binding.", "3 3 inhibitory binding. cdc25a", "inhibitory binding. cdc25a cdc25b", "binding. cdc25a cdc25b and", "cdc25b and cdc25c in turn", "and cdc25c in turn activate", "cdc25c in turn activate cdk1", "turn activate cdk1 cdk2", "activate cdk1 cdk2 and", "cdk1 cdk2 and cdk4", "cdk2 and cdk4 kinases causing", "and cdk4 kinases causing neuronal", "cdk4 kinases causing neuronal death.", "kinases causing neuronal death. consistent", "causing neuronal death. consistent with", "neuronal death. consistent with this", "death. consistent with this mechanism", "with this mechanism higher", "this mechanism higher cdc25a", "higher cdc25a cdc25b and", "cdc25b and cdc25c activities were", "and cdc25c activities were observed", "cdc25c activities were observed in", "activities were observed in human", "were observed in human alzheimer's", "observed in human alzheimer's disease", "human alzheimer's disease ad", "disease ad clinical", "clinical samples as compared", "samples as compared to", "as compared to age matched", "compared to age matched controls.", "to age matched controls. inhibition", "age matched controls. inhibition of", "matched controls. inhibition of cdc25", "controls. inhibition of cdc25 isoforms", "inhibition of cdc25 isoforms confers", "of cdc25 isoforms confers neuroprotection", "cdc25 isoforms confers neuroprotection to", "isoforms confers neuroprotection to beta", "confers neuroprotection to beta amyloid", "neuroprotection to beta amyloid toxicity", "beta amyloid toxicity which", "amyloid toxicity which underscores", "toxicity which underscores the", "which underscores the contribution of", "underscores the contribution of this", "the contribution of this pathway", "contribution of this pathway to", "of this pathway to ad", "this pathway to ad pathogenesis" ] }, { "record_id": "GLY_000594_1_1147", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8864260", "r hsa", "hsa 8864260", "r hsa 8864260" ] }, { "record_id": "GLY_000594_1_1147", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation by", "by the", "the ap", "ap 2", "family of", "of transcription", "transcription factors", "transcriptional regulation by", "regulation by the", "by the ap", "the ap 2", "2 tfap2", "tfap2 family", "family of transcription", "of transcription factors", "transcriptional regulation by the", "regulation by the ap", "by the ap 2", "ap 2 tfap2", "tfap2 family of", "family of transcription factors", "transcriptional regulation by the ap", "regulation by the ap 2", "the ap 2 tfap2", "2 tfap2 family", "tfap2 family of transcription", "factors includes", "includes five", "five proteins", "proteins in", "in mammals:", "mammals: tfap2a", "2 alpha", "2 beta", "2 gamma", "2 delta", "and tfap2e", "2 epsilon", "epsilon .", ". the", "2 family", "family transcription", "factors are", "are evolutionarily", "evolutionarily conserved", "conserved in", "in metazoans", "metazoans and", "and are", "are characterized", "characterized by", "by a", "a helix", "helix span", "span helix", "helix motif", "motif at", "at the", "the c", "c terminus", "a central", "central basic", "basic region", "and the", "the transactivation", "transactivation domain", "domain at", "the n", "n terminus.", "terminus. the", "the helix", "motif and", "the basic", "region enable", "enable dimerization", "dimerization and", "and dna", "dna binding", "eckert et", "et al.", "al. 2005", "2005 .

              ap", ".

              ap 2", "2 dimers", "dimers bind", "bind palindromic", "palindromic gc", "gc rich", "rich dna", "dna response", "response elements", "elements that", "that match", "match the", "the consensus", "consensus sequence", "sequence 5'", "5' gccnnnggc", "gccnnnggc 3'", "williams and", "and tjian", "tjian 1991a", "tjian 1991b", "1991b .", ". transcriptional", "transcriptional co", "co factors", "factors from", "from the", "the cited", "cited family", "family interact", "interact with", "with the", "domain of", "of tfap2", "factors and", "and recruit", "recruit transcription", "transcription co", "co activators", "activators ep300", "and crebbp", "to tfap2", "tfap2 bound", "bound dna", "dna elements.", "elements. cited2", "cited2 shows", "shows the", "the highest", "highest affinity", "affinity for", "for tfap2", "tfap2 proteins", "followed by", "by cited4", "while cited1", "cited1 interacts", "interacts with", "with tfap2s", "tfap2s with", "with a", "a very", "very low", "low affinity.", "affinity. mouse", "mouse embryos", "embryos defective", "defective for", "for cited2", "cited2 exhibit", "exhibit neural", "neural crest", "crest defects", "cardiac malformations", "malformations and", "and adrenal", "adrenal agenesis", "which can", "can at", "at least", "least in", "in part", "part be", "be attributed", "attributed to", "to a", "a defective", "defective tfap2", "tfap2 transactivation", "bamforth et", "al. 2001", "braganca et", "al. 2002", "al. 2003", "2003 .", "transcriptional activity", "activity of", "of ap", "dimers in", "in inhibited", "inhibited by", "by binding", "binding of", "of kctd1", "kctd1 or", "or kctd15", "kctd15 to", "to the", "2 transactivation", "ding et", "al. 2009", "zarelli and", "and dawid", "dawid 2013", "2013 .", "of tfap2a", "tfap2b and", "and tfap2c", "tfap2c is", "is negatively", "negatively regulated", "regulated by", "by sumoylation", "sumoylation mediated", "mediated by", "by ube2i", "eloranta and", "and hurst", "hurst 2002", "berlato et", "al. 2011", "impens et", "al. 2014", "bogachek et", "2014 .

              during", ".

              during embryonic", "embryonic development", "2 transcription", "factors stimulate", "stimulate proliferation", "proliferation and", "and suppress", "suppress terminal", "terminal differentiation", "differentiation in", "in a", "a cell", "cell type", "type specific", "specific manner", "2005 .

              tfap2a", ".

              tfap2a and", "tfap2c directly", "directly stimulate", "stimulate transcription", "transcription of", "of the", "the estrogen", "estrogen receptor", "receptor esr1", "esr1 gene", "mcpherson and", "and weigel", "weigel 1999", "1999 .", ". tfap2a", "tfap2a expression", "expression correlates", "correlates with", "with esr1", "esr1 expression", "expression in", "in breast", "breast cancer", "is frequently", "frequently overexpressed", "overexpressed in", "in estrogen", "estrogen positive", "positive breast", "cancer and", "and endometrial", "endometrial cancer", "deconinck et", "al. 1995", "turner et", "al. 1998", "1998 .", "as well", "well as", "as tfap2b", "tfap2b can", "can directly", "stimulate the", "the expression", "expression of", "of erbb2", "another important", "important breast", "cancer gene", "bosher et", "al. 1996", "1996 .", ". association", "association of", "tfap2a with", "the yy1", "yy1 transcription", "transcription factor", "factor significantly", "significantly increases", "increases the", "the erbb2", "erbb2 transcription", "transcription rate", "begon et", "2005 .", ". in", "in addition", "addition to", "to erbb2", "of another", "another receptor", "receptor tyrosine", "tyrosine kinase", "is also", "also stimulated", "stimulated by", "by tfap2a", "tfap2a and", "and tfap2b", "huang et", "while the", "the vegf", "vegf receptor", "kinase ligand", "ligand vegfa", "vegfa is", "is repressed", "repressed by", "ruiz et", "al. 2004", "li et", "al. 2012", "2012 .", "tfap2a stimulates", "stimulates transcription", "the transforming", "transforming growth", "growth factor", "factor alpha", "wang et", "al. 1997", "1997 .", ". tfap2c", "tfap2c regulates", "regulates egfr", "egfr in", "in luminal", "luminal breast", "de andrade", "andrade et", "al. 2016", "2016 .

              tfap2c", ".

              tfap2c plays", "plays a", "a critical", "critical role", "role in", "in maintaining", "maintaining the", "the luminal", "luminal phenotype", "phenotype in", "in human", "human breast", "and in", "in influencing", "influencing the", "luminal cell", "cell phenotype", "phenotype during", "during normal", "normal mammary", "mammary development", "cyr et", "al. 2015", "2015 .

              in", ".

              in placenta", "of both", "both subunits", "subunits of", "the human", "human chorionic", "chorionic gonadotropin", "cga and", "and cgb", "johnson et", "licalsi et", "al. 2000", "2000 .

              tfap2a", ".

              tfap2a and/or", "and/or tfap2c", "in complex", "complex with", "with cited2", "the pitx2", "pitx2 gene", "involved in", "in left", "left right", "right patterning", "patterning and", "and heart", "heart development", "2012 .

              tfap2a", "tfap2c play", "play opposing", "opposing roles", "roles in", "in transcriptional", "regulation of", "the cdkn1a", "gene locus.", "locus. while", "while tfap2a", "cdkn1a cyclin", "cyclin dependent", "dependent kinase", "kinase inhibitor", "zeng et", "williams et", "scibetta et", "al. 2010", "tfap2c represses", "represses cdkn1a", "cdkn1a transcription", "wong et", ". transcription", "the tfap2a", "tfap2a gene", "gene may", "may be", "be inhibited", "by creb", "creb and", "and e2f1", "melnikova et", "2010 .

              for", ".

              for review", "review of", "please refer", "refer to", "to eckert", "al. 2005.", "transcription factors includes", "factors includes five", "includes five proteins", "five proteins in", "proteins in mammals:", "in mammals: tfap2a", "tfap2a ap", "ap 2 alpha", "tfap2b ap", "ap 2 beta", "tfap2c ap", "ap 2 gamma", "tfap2d ap", "ap 2 delta", "delta and", "tfap2e ap", "ap 2 epsilon", "2 epsilon .", "epsilon . the", ". the ap", "ap 2 family", "2 family transcription", "family transcription factors", "transcription factors are", "factors are evolutionarily", "are evolutionarily conserved", "evolutionarily conserved in", "conserved in metazoans", "in metazoans and", "metazoans and are", "and are characterized", "are characterized by", "characterized by a", "by a helix", "a helix span", "helix span helix", "span helix motif", "helix motif at", "motif at the", "at the c", "the c terminus", "terminus a", "a central basic", "central basic region", "region and", "and the transactivation", "the transactivation domain", "transactivation domain at", "domain at the", "at the n", "the n terminus.", "n terminus. the", "terminus. the helix", "the helix span", "helix motif and", "motif and the", "and the basic", "the basic region", "basic region enable", "region enable dimerization", "enable dimerization and", "dimerization and dna", "and dna binding", "binding eckert", "eckert et al.", "et al. 2005", "al. 2005 .

              ap", "2005 .

              ap 2", ".

              ap 2 dimers", "2 dimers bind", "dimers bind palindromic", "bind palindromic gc", "palindromic gc rich", "gc rich dna", "rich dna response", "dna response elements", "response elements that", "elements that match", "that match the", "match the consensus", "the consensus sequence", "consensus sequence 5'", "sequence 5' gccnnnggc", "5' gccnnnggc 3'", "3' williams", "williams and tjian", "and tjian 1991a", "1991a williams", "and tjian 1991b", "tjian 1991b .", "1991b . transcriptional", ". transcriptional co", "transcriptional co factors", "co factors from", "factors from the", "from the cited", "the cited family", "cited family interact", "family interact with", "interact with the", "with the helix", "helix hsh", "hsh domain", "domain of tfap2", "tfap2 ap", "transcription factors and", "factors and recruit", "and recruit transcription", "recruit transcription co", "transcription co activators", "co activators ep300", "ep300 p300", "p300 and", "crebbp cbp", "cbp to", "to tfap2 bound", "tfap2 bound dna", "bound dna elements.", "dna elements. cited2", "elements. cited2 shows", "cited2 shows the", "shows the highest", "the highest affinity", "highest affinity for", "affinity for tfap2", "for tfap2 proteins", "proteins followed", "followed by cited4", "cited4 while", "while cited1 interacts", "cited1 interacts with", "interacts with tfap2s", "with tfap2s with", "tfap2s with a", "with a very", "a very low", "very low affinity.", "low affinity. mouse", "affinity. mouse embryos", "mouse embryos defective", "embryos defective for", "defective for cited2", "for cited2 exhibit", "cited2 exhibit neural", "exhibit neural crest", "neural crest defects", "defects cardiac", "cardiac malformations and", "malformations and adrenal", "and adrenal agenesis", "agenesis which", "which can at", "can at least", "at least in", "least in part", "in part be", "part be attributed", "be attributed to", "attributed to a", "to a defective", "a defective tfap2", "defective tfap2 transactivation", "transactivation bamforth", "bamforth et al.", "et al. 2001", "2001 braganca", "braganca et al.", "et al. 2002", "2002 braganca", "et al. 2003", "al. 2003 .", "2003 . transcriptional", ". transcriptional activity", "transcriptional activity of", "activity of ap", "of ap 2", "ap 2 dimers", "2 dimers in", "dimers in inhibited", "in inhibited by", "inhibited by binding", "by binding of", "binding of kctd1", "of kctd1 or", "kctd1 or kctd15", "or kctd15 to", "kctd15 to the", "to the ap", "ap 2 transactivation", "2 transactivation domain", "domain ding", "ding et al.", "et al. 2009", "2009 zarelli", "zarelli and dawid", "and dawid 2013", "dawid 2013 .", "2013 . transcriptional", "activity of tfap2a", "tfap2a tfap2b", "tfap2b and tfap2c", "and tfap2c is", "tfap2c is negatively", "is negatively regulated", "negatively regulated by", "regulated by sumoylation", "by sumoylation mediated", "sumoylation mediated by", "mediated by ube2i", "ube2i ubc9", "eloranta and hurst", "and hurst 2002", "2002 berlato", "berlato et al.", "et al. 2011", "2011 impens", "impens et al.", "et al. 2014", "2014 bogachek", "bogachek et al.", "al. 2014 .

              during", "2014 .

              during embryonic", ".

              during embryonic development", "development ap", "ap 2 transcription", "2 transcription factors", "transcription factors stimulate", "factors stimulate proliferation", "stimulate proliferation and", "proliferation and suppress", "and suppress terminal", "suppress terminal differentiation", "terminal differentiation in", "differentiation in a", "in a cell", "a cell type", "cell type specific", "type specific manner", "manner eckert", "al. 2005 .

              tfap2a", "2005 .

              tfap2a and", ".

              tfap2a and tfap2c", "and tfap2c directly", "tfap2c directly stimulate", "directly stimulate transcription", "stimulate transcription of", "transcription of the", "of the estrogen", "the estrogen receptor", "estrogen receptor esr1", "receptor esr1 gene", "gene mcpherson", "mcpherson and weigel", "and weigel 1999", "weigel 1999 .", "1999 . tfap2a", ". tfap2a expression", "tfap2a expression correlates", "expression correlates with", "correlates with esr1", "with esr1 expression", "esr1 expression in", "expression in breast", "in breast cancer", "tfap2c is frequently", "is frequently overexpressed", "frequently overexpressed in", "overexpressed in estrogen", "in estrogen positive", "estrogen positive breast", "positive breast cancer", "breast cancer and", "cancer and endometrial", "and endometrial cancer", "cancer deconinck", "deconinck et al.", "et al. 1995", "1995 turner", "turner et al.", "et al. 1998", "al. 1998 .", "1998 . tfap2a", "tfap2a tfap2c", "tfap2c as", "as well as", "well as tfap2b", "as tfap2b can", "tfap2b can directly", "can directly stimulate", "directly stimulate the", "stimulate the expression", "the expression of", "expression of erbb2", "erbb2 another", "another important breast", "important breast cancer", "breast cancer gene", "gene bosher", "bosher et al.", "et al. 1996", "al. 1996 .", "1996 . association", ". association of", "association of tfap2a", "of tfap2a with", "tfap2a with the", "with the yy1", "the yy1 transcription", "yy1 transcription factor", "transcription factor significantly", "factor significantly increases", "significantly increases the", "increases the erbb2", "the erbb2 transcription", "erbb2 transcription rate", "rate begon", "begon et al.", "al. 2005 .", "2005 . in", ". in addition", "in addition to", "addition to erbb2", "erbb2 the", "expression of another", "of another receptor", "another receptor tyrosine", "receptor tyrosine kinase", "kinase kit", "kit is", "is also stimulated", "also stimulated by", "stimulated by tfap2a", "by tfap2a and", "tfap2a and tfap2b", "tfap2b huang", "huang et al.", "while the expression", "expression of the", "of the vegf", "the vegf receptor", "vegf receptor tyrosine", "tyrosine kinase ligand", "kinase ligand vegfa", "ligand vegfa is", "vegfa is repressed", "is repressed by", "repressed by tfap2a", "tfap2a ruiz", "ruiz et al.", "et al. 2004", "2004 li", "li et al.", "et al. 2012", "al. 2012 .", "2012 . tfap2a", ". tfap2a stimulates", "tfap2a stimulates transcription", "stimulates transcription of", "of the transforming", "the transforming growth", "transforming growth factor", "growth factor alpha", "alpha tgfa", "tgfa gene", "gene wang", "wang et al.", "et al. 1997", "al. 1997 .", "1997 . tfap2c", ". tfap2c regulates", "tfap2c regulates egfr", "regulates egfr in", "egfr in luminal", "in luminal breast", "luminal breast cancer", "cancer de", "de andrade et", "andrade et al.", "et al. 2016", "al. 2016 .

              tfap2c", "2016 .

              tfap2c plays", ".

              tfap2c plays a", "plays a critical", "a critical role", "critical role in", "role in maintaining", "in maintaining the", "maintaining the luminal", "the luminal phenotype", "luminal phenotype in", "phenotype in human", "in human breast", "human breast cancer", "cancer and in", "and in influencing", "in influencing the", "influencing the luminal", "the luminal cell", "luminal cell phenotype", "cell phenotype during", "phenotype during normal", "during normal mammary", "normal mammary development", "development cyr", "cyr et al.", "et al. 2015", "al. 2015 .

              in", "2015 .

              in placenta", "placenta tfap2a", "tfap2a and tfap2c", "transcription of both", "of both subunits", "both subunits of", "subunits of the", "of the human", "the human chorionic", "human chorionic gonadotropin", "gonadotropin cga", "cga and cgb", "cgb johnson", "johnson et al.", "1997 licalsi", "licalsi et al.", "et al. 2000", "al. 2000 .

              tfap2a", "2000 .

              tfap2a and/or", ".

              tfap2a and/or tfap2c", "tfap2c in", "in complex with", "complex with cited2", "cited2 stimulate", "of the pitx2", "the pitx2 gene", "gene involved", "involved in left", "in left right", "left right patterning", "right patterning and", "patterning and heart", "and heart development", "development bamforth", "al. 2012 .

              tfap2a", "2012 .

              tfap2a and", "and tfap2c play", "tfap2c play opposing", "play opposing roles", "opposing roles in", "roles in transcriptional", "in transcriptional regulation", "transcriptional regulation of", "regulation of the", "of the cdkn1a", "cdkn1a p21", "p21 gene", "gene locus. while", "locus. while tfap2a", "while tfap2a stimulates", "the cdkn1a cyclin", "cdkn1a cyclin dependent", "cyclin dependent kinase", "dependent kinase inhibitor", "inhibitor zeng", "zeng et al.", "1997 williams", "williams et al.", "2009 scibetta", "scibetta et al.", "et al. 2010", "tfap2c represses cdkn1a", "represses cdkn1a transcription", "transcription williams", "2010 wong", "wong et al.", "2012 . transcription", ". transcription of", "of the tfap2a", "the tfap2a gene", "tfap2a gene may", "gene may be", "may be inhibited", "be inhibited by", "inhibited by creb", "by creb and", "creb and e2f1", "e2f1 melnikova", "melnikova et al.", "al. 2010 .

              for", "2010 .

              for review", ".

              for review of", "review of the", "of the ap", "2 family of", "factors please", "please refer to", "refer to eckert", "to eckert et", "et al. 2005.", "of transcription factors includes", "transcription factors includes five", "factors includes five proteins", "includes five proteins in", "five proteins in mammals:", "proteins in mammals: tfap2a", "mammals: tfap2a ap", "tfap2a ap 2", "alpha tfap2b", "tfap2b ap 2", "beta tfap2c", "tfap2c ap 2", "gamma tfap2d", "tfap2d ap 2", "2 delta and", "delta and tfap2e", "and tfap2e ap", "tfap2e ap 2", "ap 2 epsilon .", "2 epsilon . the", "epsilon . the ap", ". the ap 2", "the ap 2 family", "ap 2 family transcription", "2 family transcription factors", "family transcription factors are", "transcription factors are evolutionarily", "factors are evolutionarily conserved", "are evolutionarily conserved in", "evolutionarily conserved in metazoans", "conserved in metazoans and", "in metazoans and are", "metazoans and are characterized", "and are characterized by", "are characterized by a", "characterized by a helix", "by a helix span", "a helix span helix", "helix span helix motif", "span helix motif at", "helix motif at the", "motif at the c", "at the c terminus", "c terminus a", "terminus a central", "a central basic region", "basic region and", "region and the", "and the transactivation domain", "the transactivation domain at", "transactivation domain at the", "domain at the n", "at the n terminus.", "the n terminus. the", "n terminus. the helix", "terminus. the helix span", "the helix span helix", "span helix motif and", "helix motif and the", "motif and the basic", "and the basic region", "the basic region enable", "basic region enable dimerization", "region enable dimerization and", "enable dimerization and dna", "dimerization and dna binding", "dna binding eckert", "binding eckert et", "eckert et al. 2005", "et al. 2005 .

              ap", "al. 2005 .

              ap 2", "2005 .

              ap 2 dimers", ".

              ap 2 dimers bind", "2 dimers bind palindromic", "dimers bind palindromic gc", "bind palindromic gc rich", "palindromic gc rich dna", "gc rich dna response", "rich dna response elements", "dna response elements that", "response elements that match", "elements that match the", "that match the consensus", "match the consensus sequence", "the consensus sequence 5'", "consensus sequence 5' gccnnnggc", "sequence 5' gccnnnggc 3'", "gccnnnggc 3' williams", "3' williams and", "williams and tjian 1991a", "tjian 1991a williams", "1991a williams and", "williams and tjian 1991b", "and tjian 1991b .", "tjian 1991b . transcriptional", "1991b . transcriptional co", ". transcriptional co factors", "transcriptional co factors from", "co factors from the", "factors from the cited", "from the cited family", "the cited family interact", "cited family interact with", "family interact with the", "interact with the helix", "with the helix span", "span helix hsh", "hsh domain of", "of tfap2 ap", "tfap2 ap 2", "of transcription factors and", "transcription factors and recruit", "factors and recruit transcription", "and recruit transcription co", "recruit transcription co activators", "transcription co activators ep300", "activators ep300 p300", "p300 and crebbp", "and crebbp cbp", "cbp to tfap2", "to tfap2 bound dna", "tfap2 bound dna elements.", "bound dna elements. cited2", "dna elements. cited2 shows", "elements. cited2 shows the", "cited2 shows the highest", "shows the highest affinity", "the highest affinity for", "highest affinity for tfap2", "affinity for tfap2 proteins", "tfap2 proteins followed", "proteins followed by", "by cited4 while", "cited4 while cited1", "while cited1 interacts with", "cited1 interacts with tfap2s", "interacts with tfap2s with", "with tfap2s with a", "tfap2s with a very", "with a very low", "a very low affinity.", "very low affinity. mouse", "low affinity. mouse embryos", "affinity. mouse embryos defective", "mouse embryos defective for", "embryos defective for cited2", "defective for cited2 exhibit", "for cited2 exhibit neural", "cited2 exhibit neural crest", "exhibit neural crest defects", "crest defects cardiac", "defects cardiac malformations", "cardiac malformations and adrenal", "malformations and adrenal agenesis", "adrenal agenesis which", "agenesis which can", "which can at least", "can at least in", "at least in part", "least in part be", "in part be attributed", "part be attributed to", "be attributed to a", "attributed to a defective", "to a defective tfap2", "a defective tfap2 transactivation", "tfap2 transactivation bamforth", "transactivation bamforth et", "bamforth et al. 2001", "al. 2001 braganca", "2001 braganca et", "braganca et al. 2002", "al. 2002 braganca", "2002 braganca et", "braganca et al. 2003", "et al. 2003 .", "al. 2003 . transcriptional", "2003 . transcriptional activity", ". transcriptional activity of", "transcriptional activity of ap", "activity of ap 2", "of ap 2 dimers", "ap 2 dimers in", "2 dimers in inhibited", "dimers in inhibited by", "in inhibited by binding", "inhibited by binding of", "by binding of kctd1", "binding of kctd1 or", "of kctd1 or kctd15", "kctd1 or kctd15 to", "or kctd15 to the", "kctd15 to the ap", "to the ap 2", "the ap 2 transactivation", "ap 2 transactivation domain", "transactivation domain ding", "domain ding et", "ding et al. 2009", "al. 2009 zarelli", "2009 zarelli and", "zarelli and dawid 2013", "and dawid 2013 .", "dawid 2013 . transcriptional", "2013 . transcriptional activity", "transcriptional activity of tfap2a", "of tfap2a tfap2b", "tfap2a tfap2b and", "tfap2b and tfap2c is", "and tfap2c is negatively", "tfap2c is negatively regulated", "is negatively regulated by", "negatively regulated by sumoylation", "regulated by sumoylation mediated", "by sumoylation mediated by", "sumoylation mediated by ube2i", "by ube2i ubc9", "ubc9 eloranta", "eloranta and hurst 2002", "hurst 2002 berlato", "2002 berlato et", "berlato et al. 2011", "al. 2011 impens", "2011 impens et", "impens et al. 2014", "al. 2014 bogachek", "2014 bogachek et", "bogachek et al. 2014", "et al. 2014 .

              during", "al. 2014 .

              during embryonic", "2014 .

              during embryonic development", "embryonic development ap", "development ap 2", "ap 2 transcription factors", "2 transcription factors stimulate", "transcription factors stimulate proliferation", "factors stimulate proliferation and", "stimulate proliferation and suppress", "proliferation and suppress terminal", "and suppress terminal differentiation", "suppress terminal differentiation in", "terminal differentiation in a", "differentiation in a cell", "in a cell type", "a cell type specific", "cell type specific manner", "specific manner eckert", "manner eckert et", "et al. 2005 .

              tfap2a", "al. 2005 .

              tfap2a and", "2005 .

              tfap2a and tfap2c", ".

              tfap2a and tfap2c directly", "and tfap2c directly stimulate", "tfap2c directly stimulate transcription", "directly stimulate transcription of", "stimulate transcription of the", "transcription of the estrogen", "of the estrogen receptor", "the estrogen receptor esr1", "estrogen receptor esr1 gene", "esr1 gene mcpherson", "gene mcpherson and", "mcpherson and weigel 1999", "and weigel 1999 .", "weigel 1999 . tfap2a", "1999 . tfap2a expression", ". tfap2a expression correlates", "tfap2a expression correlates with", "expression correlates with esr1", "correlates with esr1 expression", "with esr1 expression in", "esr1 expression in breast", "expression in breast cancer", "cancer and tfap2c", "and tfap2c is frequently", "tfap2c is frequently overexpressed", "is frequently overexpressed in", "frequently overexpressed in estrogen", "overexpressed in estrogen positive", "in estrogen positive breast", "estrogen positive breast cancer", "positive breast cancer and", "breast cancer and endometrial", "cancer and endometrial cancer", "endometrial cancer deconinck", "cancer deconinck et", "deconinck et al. 1995", "al. 1995 turner", "1995 turner et", "turner et al. 1998", "et al. 1998 .", "al. 1998 . tfap2a", ". tfap2a tfap2c", "tfap2c as well", "as well as tfap2b", "well as tfap2b can", "as tfap2b can directly", "tfap2b can directly stimulate", "can directly stimulate the", "directly stimulate the expression", "stimulate the expression of", "the expression of erbb2", "of erbb2 another", "erbb2 another important", "another important breast cancer", "important breast cancer gene", "cancer gene bosher", "gene bosher et", "bosher et al. 1996", "et al. 1996 .", "al. 1996 . association", "1996 . association of", ". association of tfap2a", "association of tfap2a with", "of tfap2a with the", "tfap2a with the yy1", "with the yy1 transcription", "the yy1 transcription factor", "yy1 transcription factor significantly", "transcription factor significantly increases", "factor significantly increases the", "significantly increases the erbb2", "increases the erbb2 transcription", "the erbb2 transcription rate", "transcription rate begon", "rate begon et", "begon et al. 2005", "et al. 2005 .", "al. 2005 . in", "2005 . in addition", ". in addition to", "in addition to erbb2", "to erbb2 the", "erbb2 the expression", "the expression of another", "expression of another receptor", "of another receptor tyrosine", "another receptor tyrosine kinase", "tyrosine kinase kit", "kit is also", "is also stimulated by", "also stimulated by tfap2a", "stimulated by tfap2a and", "by tfap2a and tfap2b", "and tfap2b huang", "tfap2b huang et", "huang et al. 1998", "1998 while", "while the expression of", "the expression of the", "expression of the vegf", "of the vegf receptor", "the vegf receptor tyrosine", "vegf receptor tyrosine kinase", "receptor tyrosine kinase ligand", "tyrosine kinase ligand vegfa", "kinase ligand vegfa is", "ligand vegfa is repressed", "vegfa is repressed by", "is repressed by tfap2a", "by tfap2a ruiz", "tfap2a ruiz et", "ruiz et al. 2004", "al. 2004 li", "2004 li et", "li et al. 2012", "et al. 2012 .", "al. 2012 . tfap2a", "2012 . tfap2a stimulates", ". tfap2a stimulates transcription", "tfap2a stimulates transcription of", "stimulates transcription of the", "transcription of the transforming", "of the transforming growth", "the transforming growth factor", "transforming growth factor alpha", "factor alpha tgfa", "gene wang et", "wang et al. 1997", "et al. 1997 .", "al. 1997 . tfap2c", "1997 . tfap2c regulates", ". tfap2c regulates egfr", "tfap2c regulates egfr in", "regulates egfr in luminal", "egfr in luminal breast", "in luminal breast cancer", "breast cancer de", "cancer de andrade", "de andrade et al.", "andrade et al. 2016", "et al. 2016 .

              tfap2c", "al. 2016 .

              tfap2c plays", "2016 .

              tfap2c plays a", ".

              tfap2c plays a critical", "plays a critical role", "a critical role in", "critical role in maintaining", "role in maintaining the", "in maintaining the luminal", "maintaining the luminal phenotype", "the luminal phenotype in", "luminal phenotype in human", "phenotype in human breast", "in human breast cancer", "human breast cancer and", "breast cancer and in", "cancer and in influencing", "and in influencing the", "in influencing the luminal", "influencing the luminal cell", "the luminal cell phenotype", "luminal cell phenotype during", "cell phenotype during normal", "phenotype during normal mammary", "during normal mammary development", "mammary development cyr", "development cyr et", "cyr et al. 2015", "et al. 2015 .

              in", "al. 2015 .

              in placenta", ".

              in placenta tfap2a", "placenta tfap2a and", "tfap2a and tfap2c directly", "stimulate transcription of both", "transcription of both subunits", "of both subunits of", "both subunits of the", "subunits of the human", "of the human chorionic", "the human chorionic gonadotropin", "chorionic gonadotropin cga", "gonadotropin cga and", "and cgb johnson", "cgb johnson et", "johnson et al. 1997", "al. 1997 licalsi", "1997 licalsi et", "licalsi et al. 2000", "et al. 2000 .

              tfap2a", "al. 2000 .

              tfap2a and/or", "2000 .

              tfap2a and/or tfap2c", "and/or tfap2c in", "tfap2c in complex", "in complex with cited2", "with cited2 stimulate", "cited2 stimulate transcription", "transcription of the pitx2", "of the pitx2 gene", "pitx2 gene involved", "gene involved in", "involved in left right", "in left right patterning", "left right patterning and", "right patterning and heart", "patterning and heart development", "heart development bamforth", "development bamforth et", "bamforth et al. 2004", "et al. 2012 .

              tfap2a", "al. 2012 .

              tfap2a and", "2012 .

              tfap2a and tfap2c", ".

              tfap2a and tfap2c play", "and tfap2c play opposing", "tfap2c play opposing roles", "play opposing roles in", "opposing roles in transcriptional", "roles in transcriptional regulation", "in transcriptional regulation of", "transcriptional regulation of the", "regulation of the cdkn1a", "the cdkn1a p21", "p21 gene locus.", "gene locus. while tfap2a", "locus. while tfap2a stimulates", "while tfap2a stimulates transcription", "transcription of the cdkn1a", "of the cdkn1a cyclin", "the cdkn1a cyclin dependent", "cdkn1a cyclin dependent kinase", "cyclin dependent kinase inhibitor", "kinase inhibitor zeng", "inhibitor zeng et", "zeng et al. 1997", "al. 1997 williams", "1997 williams et", "williams et al. 2009", "al. 2009 scibetta", "2009 scibetta et", "scibetta et al. 2010", "2010 tfap2c", "tfap2c represses cdkn1a transcription", "cdkn1a transcription williams", "transcription williams et", "al. 2010 wong", "2010 wong et", "wong et al. 2012", "al. 2012 . transcription", "2012 . transcription of", ". transcription of the", "transcription of the tfap2a", "of the tfap2a gene", "the tfap2a gene may", "tfap2a gene may be", "gene may be inhibited", "may be inhibited by", "be inhibited by creb", "inhibited by creb and", "by creb and e2f1", "and e2f1 melnikova", "e2f1 melnikova et", "melnikova et al. 2010", "et al. 2010 .

              for", "al. 2010 .

              for review", "2010 .

              for review of", ".

              for review of the", "review of the ap", "of the ap 2", "ap 2 family of", "2 family of transcription", "transcription factors please", "factors please refer", "please refer to eckert", "refer to eckert et", "to eckert et al.", "eckert et al. 2005.", "family of transcription factors includes", "of transcription factors includes five", "transcription factors includes five proteins", "factors includes five proteins in", "includes five proteins in mammals:", "five proteins in mammals: tfap2a", "in mammals: tfap2a ap", "mammals: tfap2a ap 2", "tfap2a ap 2 alpha", "2 alpha tfap2b", "tfap2b ap 2 beta", "2 beta tfap2c", "tfap2c ap 2 gamma", "2 gamma tfap2d", "tfap2d ap 2 delta", "ap 2 delta and", "2 delta and tfap2e", "and tfap2e ap 2", "tfap2e ap 2 epsilon", "ap 2 epsilon . the", "2 epsilon . the ap", "epsilon . the ap 2", ". the ap 2 family", "the ap 2 family transcription", "ap 2 family transcription factors", "2 family transcription factors are", "family transcription factors are evolutionarily", "transcription factors are evolutionarily conserved", "factors are evolutionarily conserved in", "are evolutionarily conserved in metazoans", "evolutionarily conserved in metazoans and", "conserved in metazoans and are", "in metazoans and are characterized", "metazoans and are characterized by", "and are characterized by a", "are characterized by a helix", "characterized by a helix span", "by a helix span helix", "a helix span helix motif", "helix span helix motif at", "span helix motif at the", "helix motif at the c", "motif at the c terminus", "the c terminus a", "c terminus a central", "terminus a central basic", "central basic region and", "basic region and the", "region and the transactivation", "and the transactivation domain at", "the transactivation domain at the", "transactivation domain at the n", "domain at the n terminus.", "at the n terminus. the", "the n terminus. the helix", "n terminus. the helix span", "terminus. the helix span helix", "the helix span helix motif", "helix span helix motif and", "span helix motif and the", "helix motif and the basic", "motif and the basic region", "and the basic region enable", "the basic region enable dimerization", "basic region enable dimerization and", "region enable dimerization and dna", "enable dimerization and dna binding", "and dna binding eckert", "dna binding eckert et", "binding eckert et al.", "eckert et al. 2005 .

              ap", "et al. 2005 .

              ap 2", "al. 2005 .

              ap 2 dimers", "2005 .

              ap 2 dimers bind", ".

              ap 2 dimers bind palindromic", "2 dimers bind palindromic gc", "dimers bind palindromic gc rich", "bind palindromic gc rich dna", "palindromic gc rich dna response", "gc rich dna response elements", "rich dna response elements that", "dna response elements that match", "response elements that match the", "elements that match the consensus", "that match the consensus sequence", "match the consensus sequence 5'", "the consensus sequence 5' gccnnnggc", "consensus sequence 5' gccnnnggc 3'", "5' gccnnnggc 3' williams", "gccnnnggc 3' williams and", "3' williams and tjian", "and tjian 1991a williams", "tjian 1991a williams and", "1991a williams and tjian", "williams and tjian 1991b .", "and tjian 1991b . transcriptional", "tjian 1991b . transcriptional co", "1991b . transcriptional co factors", ". transcriptional co factors from", "transcriptional co factors from the", "co factors from the cited", "factors from the cited family", "from the cited family interact", "the cited family interact with", "cited family interact with the", "family interact with the helix", "interact with the helix span", "with the helix span helix", "helix span helix hsh", "helix hsh domain", "hsh domain of tfap2", "domain of tfap2 ap", "of tfap2 ap 2", "family of transcription factors and", "of transcription factors and recruit", "transcription factors and recruit transcription", "factors and recruit transcription co", "and recruit transcription co activators", "recruit transcription co activators ep300", "co activators ep300 p300", "ep300 p300 and", "crebbp cbp to", "cbp to tfap2 bound", "to tfap2 bound dna elements.", "tfap2 bound dna elements. cited2", "bound dna elements. cited2 shows", "dna elements. cited2 shows the", "elements. cited2 shows the highest", "cited2 shows the highest affinity", "shows the highest affinity for", "the highest affinity for tfap2", "highest affinity for tfap2 proteins", "for tfap2 proteins followed", "tfap2 proteins followed by", "proteins followed by cited4", "followed by cited4 while", "by cited4 while cited1", "cited4 while cited1 interacts", "while cited1 interacts with tfap2s", "cited1 interacts with tfap2s with", "interacts with tfap2s with a", "with tfap2s with a very", "tfap2s with a very low", "with a very low affinity.", "a very low affinity. mouse", "very low affinity. mouse embryos", "low affinity. mouse embryos defective", "affinity. mouse embryos defective for", "mouse embryos defective for cited2", "embryos defective for cited2 exhibit", "defective for cited2 exhibit neural", "for cited2 exhibit neural crest", "cited2 exhibit neural crest defects", "neural crest defects cardiac", "crest defects cardiac malformations", "defects cardiac malformations and", "cardiac malformations and adrenal agenesis", "and adrenal agenesis which", "adrenal agenesis which can", "agenesis which can at", "which can at least in", "can at least in part", "at least in part be", "least in part be attributed", "in part be attributed to", "part be attributed to a", "be attributed to a defective", "attributed to a defective tfap2", "to a defective tfap2 transactivation", "defective tfap2 transactivation bamforth", "tfap2 transactivation bamforth et", "transactivation bamforth et al.", "et al. 2001 braganca", "al. 2001 braganca et", "2001 braganca et al.", "et al. 2002 braganca", "al. 2002 braganca et", "2002 braganca et al.", "braganca et al. 2003 .", "et al. 2003 . transcriptional", "al. 2003 . transcriptional activity", "2003 . transcriptional activity of", ". transcriptional activity of ap", "transcriptional activity of ap 2", "activity of ap 2 dimers", "of ap 2 dimers in", "ap 2 dimers in inhibited", "2 dimers in inhibited by", "dimers in inhibited by binding", "in inhibited by binding of", "inhibited by binding of kctd1", "by binding of kctd1 or", "binding of kctd1 or kctd15", "of kctd1 or kctd15 to", "kctd1 or kctd15 to the", "or kctd15 to the ap", "kctd15 to the ap 2", "to the ap 2 transactivation", "the ap 2 transactivation domain", "2 transactivation domain ding", "transactivation domain ding et", "domain ding et al.", "et al. 2009 zarelli", "al. 2009 zarelli and", "2009 zarelli and dawid", "zarelli and dawid 2013 .", "and dawid 2013 . transcriptional", "dawid 2013 . transcriptional activity", "2013 . transcriptional activity of", ". transcriptional activity of tfap2a", "activity of tfap2a tfap2b", "of tfap2a tfap2b and", "tfap2a tfap2b and tfap2c", "tfap2b and tfap2c is negatively", "and tfap2c is negatively regulated", "tfap2c is negatively regulated by", "is negatively regulated by sumoylation", "negatively regulated by sumoylation mediated", "regulated by sumoylation mediated by", "by sumoylation mediated by ube2i", "mediated by ube2i ubc9", "ubc9 eloranta and", "and hurst 2002 berlato", "hurst 2002 berlato et", "2002 berlato et al.", "et al. 2011 impens", "al. 2011 impens et", "2011 impens et al.", "et al. 2014 bogachek", "al. 2014 bogachek et", "2014 bogachek et al.", "bogachek et al. 2014 .

              during", "et al. 2014 .

              during embryonic", "al. 2014 .

              during embryonic development", ".

              during embryonic development ap", "embryonic development ap 2", "development ap 2 transcription", "ap 2 transcription factors stimulate", "2 transcription factors stimulate proliferation", "transcription factors stimulate proliferation and", "factors stimulate proliferation and suppress", "stimulate proliferation and suppress terminal", "proliferation and suppress terminal differentiation", "and suppress terminal differentiation in", "suppress terminal differentiation in a", "terminal differentiation in a cell", "differentiation in a cell type", "in a cell type specific", "a cell type specific manner", "type specific manner eckert", "specific manner eckert et", "manner eckert et al.", "eckert et al. 2005 .

              tfap2a", "et al. 2005 .

              tfap2a and", "al. 2005 .

              tfap2a and tfap2c", "2005 .

              tfap2a and tfap2c directly", ".

              tfap2a and tfap2c directly stimulate", "and tfap2c directly stimulate transcription", "tfap2c directly stimulate transcription of", "directly stimulate transcription of the", "stimulate transcription of the estrogen", "transcription of the estrogen receptor", "of the estrogen receptor esr1", "the estrogen receptor esr1 gene", "receptor esr1 gene mcpherson", "esr1 gene mcpherson and", "gene mcpherson and weigel", "mcpherson and weigel 1999 .", "and weigel 1999 . tfap2a", "weigel 1999 . tfap2a expression", "1999 . tfap2a expression correlates", ". tfap2a expression correlates with", "tfap2a expression correlates with esr1", "expression correlates with esr1 expression", "correlates with esr1 expression in", "with esr1 expression in breast", "esr1 expression in breast cancer", "in breast cancer and", "breast cancer and tfap2c", "cancer and tfap2c is", "and tfap2c is frequently overexpressed", "tfap2c is frequently overexpressed in", "is frequently overexpressed in estrogen", "frequently overexpressed in estrogen positive", "overexpressed in estrogen positive breast", "in estrogen positive breast cancer", "estrogen positive breast cancer and", "positive breast cancer and endometrial", "breast cancer and endometrial cancer", "and endometrial cancer deconinck", "endometrial cancer deconinck et", "cancer deconinck et al.", "et al. 1995 turner", "al. 1995 turner et", "1995 turner et al.", "turner et al. 1998 .", "et al. 1998 . tfap2a", "1998 . tfap2a tfap2c", "tfap2a tfap2c as", "tfap2c as well as", "as well as tfap2b can", "well as tfap2b can directly", "as tfap2b can directly stimulate", "tfap2b can directly stimulate the", "can directly stimulate the expression", "directly stimulate the expression of", "stimulate the expression of erbb2", "expression of erbb2 another", "of erbb2 another important", "erbb2 another important breast", "another important breast cancer gene", "breast cancer gene bosher", "cancer gene bosher et", "gene bosher et al.", "bosher et al. 1996 .", "et al. 1996 . association", "al. 1996 . association of", "1996 . association of tfap2a", ". association of tfap2a with", "association of tfap2a with the", "of tfap2a with the yy1", "tfap2a with the yy1 transcription", "with the yy1 transcription factor", "the yy1 transcription factor significantly", "yy1 transcription factor significantly increases", "transcription factor significantly increases the", "factor significantly increases the erbb2", "significantly increases the erbb2 transcription", "increases the erbb2 transcription rate", "erbb2 transcription rate begon", "transcription rate begon et", "rate begon et al.", "begon et al. 2005 .", "et al. 2005 . in", "al. 2005 . in addition", "2005 . in addition to", ". in addition to erbb2", "addition to erbb2 the", "to erbb2 the expression", "erbb2 the expression of", "the expression of another receptor", "expression of another receptor tyrosine", "of another receptor tyrosine kinase", "receptor tyrosine kinase kit", "kinase kit is", "kit is also stimulated", "is also stimulated by tfap2a", "also stimulated by tfap2a and", "stimulated by tfap2a and tfap2b", "tfap2a and tfap2b huang", "and tfap2b huang et", "tfap2b huang et al.", "al. 1998 while", "1998 while the", "while the expression of the", "the expression of the vegf", "expression of the vegf receptor", "of the vegf receptor tyrosine", "the vegf receptor tyrosine kinase", "vegf receptor tyrosine kinase ligand", "receptor tyrosine kinase ligand vegfa", "tyrosine kinase ligand vegfa is", "kinase ligand vegfa is repressed", "ligand vegfa is repressed by", "vegfa is repressed by tfap2a", "repressed by tfap2a ruiz", "by tfap2a ruiz et", "tfap2a ruiz et al.", "et al. 2004 li", "al. 2004 li et", "2004 li et al.", "li et al. 2012 .", "et al. 2012 . tfap2a", "al. 2012 . tfap2a stimulates", "2012 . tfap2a stimulates transcription", ". tfap2a stimulates transcription of", "tfap2a stimulates transcription of the", "stimulates transcription of the transforming", "transcription of the transforming growth", "of the transforming growth factor", "the transforming growth factor alpha", "growth factor alpha tgfa", "alpha tgfa gene", "tgfa gene wang", "gene wang et al.", "wang et al. 1997 .", "et al. 1997 . tfap2c", "al. 1997 . tfap2c regulates", "1997 . tfap2c regulates egfr", ". tfap2c regulates egfr in", "tfap2c regulates egfr in luminal", "regulates egfr in luminal breast", "egfr in luminal breast cancer", "luminal breast cancer de", "breast cancer de andrade", "cancer de andrade et", "de andrade et al. 2016", "andrade et al. 2016 .

              tfap2c", "et al. 2016 .

              tfap2c plays", "al. 2016 .

              tfap2c plays a", "2016 .

              tfap2c plays a critical", ".

              tfap2c plays a critical role", "plays a critical role in", "a critical role in maintaining", "critical role in maintaining the", "role in maintaining the luminal", "in maintaining the luminal phenotype", "maintaining the luminal phenotype in", "the luminal phenotype in human", "luminal phenotype in human breast", "phenotype in human breast cancer", "in human breast cancer and", "human breast cancer and in", "breast cancer and in influencing", "cancer and in influencing the", "and in influencing the luminal", "in influencing the luminal cell", "influencing the luminal cell phenotype", "the luminal cell phenotype during", "luminal cell phenotype during normal", "cell phenotype during normal mammary", "phenotype during normal mammary development", "normal mammary development cyr", "mammary development cyr et", "development cyr et al.", "cyr et al. 2015 .

              in", "et al. 2015 .

              in placenta", "2015 .

              in placenta tfap2a", ".

              in placenta tfap2a and", "placenta tfap2a and tfap2c", "tfap2a and tfap2c directly stimulate", "directly stimulate transcription of both", "stimulate transcription of both subunits", "transcription of both subunits of", "of both subunits of the", "both subunits of the human", "subunits of the human chorionic", "of the human chorionic gonadotropin", "human chorionic gonadotropin cga", "chorionic gonadotropin cga and", "gonadotropin cga and cgb", "cga and cgb johnson", "and cgb johnson et", "cgb johnson et al.", "et al. 1997 licalsi", "al. 1997 licalsi et", "1997 licalsi et al.", "licalsi et al. 2000 .

              tfap2a", "et al. 2000 .

              tfap2a and/or", "al. 2000 .

              tfap2a and/or tfap2c", ".

              tfap2a and/or tfap2c in", "and/or tfap2c in complex", "tfap2c in complex with", "complex with cited2 stimulate", "with cited2 stimulate transcription", "cited2 stimulate transcription of", "stimulate transcription of the pitx2", "transcription of the pitx2 gene", "the pitx2 gene involved", "pitx2 gene involved in", "gene involved in left", "involved in left right patterning", "in left right patterning and", "left right patterning and heart", "right patterning and heart development", "and heart development bamforth", "heart development bamforth et", "development bamforth et al.", "li et al. 2012 .

              tfap2a", "et al. 2012 .

              tfap2a and", "al. 2012 .

              tfap2a and tfap2c", "2012 .

              tfap2a and tfap2c play", ".

              tfap2a and tfap2c play opposing", "and tfap2c play opposing roles", "tfap2c play opposing roles in", "play opposing roles in transcriptional", "opposing roles in transcriptional regulation", "roles in transcriptional regulation of", "in transcriptional regulation of the", "transcriptional regulation of the cdkn1a", "of the cdkn1a p21", "cdkn1a p21 gene", "p21 gene locus. while", "gene locus. while tfap2a stimulates", "locus. while tfap2a stimulates transcription", "while tfap2a stimulates transcription of", "stimulates transcription of the cdkn1a", "transcription of the cdkn1a cyclin", "of the cdkn1a cyclin dependent", "the cdkn1a cyclin dependent kinase", "cdkn1a cyclin dependent kinase inhibitor", "dependent kinase inhibitor zeng", "kinase inhibitor zeng et", "inhibitor zeng et al.", "et al. 1997 williams", "al. 1997 williams et", "1997 williams et al.", "et al. 2009 scibetta", "al. 2009 scibetta et", "2009 scibetta et al.", "al. 2010 tfap2c", "2010 tfap2c represses", "represses cdkn1a transcription williams", "cdkn1a transcription williams et", "transcription williams et al.", "et al. 2010 wong", "al. 2010 wong et", "2010 wong et al.", "wong et al. 2012 .", "et al. 2012 . transcription", "al. 2012 . transcription of", "2012 . transcription of the", ". transcription of the tfap2a", "transcription of the tfap2a gene", "of the tfap2a gene may", "the tfap2a gene may be", "tfap2a gene may be inhibited", "gene may be inhibited by", "may be inhibited by creb", "be inhibited by creb and", "inhibited by creb and e2f1", "creb and e2f1 melnikova", "and e2f1 melnikova et", "e2f1 melnikova et al.", "melnikova et al. 2010 .

              for", "et al. 2010 .

              for review", "al. 2010 .

              for review of", "2010 .

              for review of the", ".

              for review of the ap", "review of the ap 2", "of the ap 2 family", "the ap 2 family of", "ap 2 family of transcription", "2 family of transcription factors", "of transcription factors please", "transcription factors please refer", "factors please refer to", "please refer to eckert et", "refer to eckert et al.", "to eckert et al. 2005." ] }, { "record_id": "GLY_000594_1_1148", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8866376", "r hsa", "hsa 8866376", "r hsa 8866376" ] }, { "record_id": "GLY_000594_1_1148", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "reelin signalling", "signalling pathway", "reelin signalling pathway", "is an", "an extracellular", "multifunctional signal", "signal glycoprotein", "glycoprotein that", "that controls", "controls not", "not only", "only the", "the positioning", "positioning of", "of neurons", "neurons in", "in the", "the developing", "developing brain", "but also", "also their", "their growth", "and synaptic", "synaptic activity", "activity in", "the adult", "adult brain", "stranahan et", "et al.", "al. 2013", "2013 .", ". abnormal", "abnormal reelin", "reelin expression", "expression in", "the brain", "brain is", "is implicated", "implicated in", "in a", "a number", "number of", "of neuropsychiatric", "neuropsychiatric disorders", "disorders including", "including autism", "bipolar disorder", "disorder and", "and alzheimer's", "alzheimer's disease", "folsom &", "& fatemi", "reelin reln", "reln is", "is an extracellular", "extracellular multifunctional", "multifunctional signal glycoprotein", "signal glycoprotein that", "glycoprotein that controls", "that controls not", "controls not only", "not only the", "only the positioning", "the positioning of", "positioning of neurons", "of neurons in", "neurons in the", "in the developing", "the developing brain", "brain but", "but also their", "also their growth", "growth maturation", "maturation and", "and synaptic activity", "synaptic activity in", "activity in the", "in the adult", "the adult brain", "brain stranahan", "stranahan et al.", "et al. 2013", "al. 2013 .", "2013 . abnormal", ". abnormal reelin", "abnormal reelin expression", "reelin expression in", "expression in the", "in the brain", "the brain is", "brain is implicated", "is implicated in", "implicated in a", "in a number", "a number of", "number of neuropsychiatric", "of neuropsychiatric disorders", "neuropsychiatric disorders including", "disorders including autism", "autism schizophrenia", "schizophrenia bipolar", "bipolar disorder and", "disorder and alzheimer's", "and alzheimer's disease", "disease folsom", "folsom & fatemi", "fatemi 2013", "reln is an", "an extracellular multifunctional", "extracellular multifunctional signal", "multifunctional signal glycoprotein that", "signal glycoprotein that controls", "glycoprotein that controls not", "that controls not only", "controls not 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"synaptic activity in the adult", "activity in the adult brain", "the adult brain stranahan", "adult brain stranahan et", "brain stranahan et al.", "stranahan et al. 2013 .", "et al. 2013 . abnormal", "al. 2013 . abnormal reelin", "2013 . abnormal reelin expression", ". abnormal reelin expression in", "abnormal reelin expression in the", "reelin expression in the brain", "expression in the brain is", "in the brain is implicated", "the brain is implicated in", "brain is implicated in a", "is implicated in a number", "implicated in a number of", "in a number of neuropsychiatric", "a number of neuropsychiatric disorders", "number of neuropsychiatric disorders including", "of neuropsychiatric disorders including autism", "disorders including autism schizophrenia", "autism schizophrenia bipolar", "schizophrenia bipolar disorder and", "bipolar disorder and alzheimer's disease", "and alzheimer's disease folsom", "alzheimer's disease folsom &", "disease folsom & fatemi", "folsom & fatemi 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by", "is repressed by tfap2a", "by tfap2a ruiz", "tfap2a ruiz et", "ruiz et al. 2004", "al. 2004 li", "2004 li et", "li et al. 2012", "et al. 2012 .", "al. 2012 . tfap2a", "2012 . tfap2a stimulates", ". tfap2a stimulates transcription", "tfap2a stimulates transcription of", "stimulates transcription of the", "transcription of the transforming", "of the transforming growth", "the transforming growth factor", "transforming growth factor alpha", "factor alpha tgfa", "gene wang et", "wang et al. 1997", "et al. 1997 .", "al. 1997 . tfap2c", "1997 . tfap2c regulates", ". tfap2c regulates egfr", "tfap2c regulates egfr expression", "regulates egfr expression in", "egfr expression in luminal", "expression in luminal breast", "in luminal breast cancer", "breast cancer de", "cancer de andrade", "de andrade et al.", "andrade et al. 2016", "et al. 2016 .", "al. 2016 . in", "2016 . in placenta", "in placenta tfap2a", "placenta tfap2a and", "stimulate transcription of both", "transcription of both 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domain", "transcription activation domain a", "activation domain a basic", "domain a basic leucine", "basic leucine zipper bzip", "zipper bzip domain", "bzip domain that promotes", "domain that promotes dimerization and", "that promotes dimerization and dna", "promotes dimerization and dna binding", "and dna binding and", "dna binding and a", "binding and a transmembrane", "and a transmembrane domain that", "a transmembrane domain that anchors", "transmembrane domain that anchors the", "domain that anchors the protein", "that anchors the protein to", "anchors the protein to the", "the protein to the membrane", "protein to the membrane of", "to the membrane of the", "the membrane of the endoplasmic", "membrane of the endoplasmic reticulum", "the endoplasmic reticulum er", "er reviewed in", "reviewed in asada et al.", "in asada et al. 2011", "et al. 2011 chan", "al. 2011 chan et", "2011 chan et al.", "et al. 2011 kondo", "al. 2011 kondo et", "2011 kondo et al.", "et al. 2011 fox", "al. 2011 fox and", "2011 fox and andrew", "fox and andrew 2015 .", "and andrew 2015 . the", "andrew 2015 . the family", "2015 . the family includes", ". the family includes creb3", "family includes creb3 luman", "creb3l2 bbf2h7 tisp40", "creb h and", "h and creb3l4", "and creb3l4 creb4 .", "creb3l4 creb4 . activation", "creb4 . activation of the", ". activation of the proteins", "activation of the proteins occurs", "of the proteins occurs when", "the proteins occurs when they", "proteins occurs when they transit", "occurs when they transit from", "when they transit from the", "they transit from the er", "transit from the er to", "from the er to the", "the er to the golgi", "er to the golgi and", "to the golgi and are", "the golgi and are cleaved", "golgi and are cleaved sequentially", "and are cleaved sequentially by", "are cleaved sequentially by the", "cleaved sequentially by the golgi", "sequentially by the golgi resident", "by the golgi resident proteases", "the golgi resident proteases mbtps1", "resident proteases mbtps1 s1p", "mbtps1 s1p and", "s2p a process", "a process known as regulated", "process known as regulated intramembrane", "known as regulated intramembrane proteolysis", "as regulated intramembrane proteolysis that", "regulated intramembrane proteolysis that releases", "intramembrane proteolysis that releases the", "proteolysis that releases the cytoplasmic", "that releases the cytoplasmic region", "releases the cytoplasmic region of", "the cytoplasmic region of the", "cytoplasmic region of the protein", "region of the protein containing", "of the protein containing the", "the protein containing the transcription", "protein containing the transcription activation", "containing the transcription activation domain", "the transcription activation domain and", "transcription activation domain and the", "activation domain and the bzip", "domain and the bzip domain.", "and the bzip domain. this", "the bzip domain. this protein", "bzip domain. this protein fragment", "domain. this protein fragment then", "this protein fragment then transits", "protein fragment then transits from", "fragment then transits from the", "then transits from the cytosol", "transits from the cytosol to", "from the cytosol to the", "the cytosol to the nucleus", "cytosol to the nucleus where", "to the nucleus where it", "the nucleus where it activates", "nucleus where it activates transcription", "where it activates transcription of", "it activates transcription of target", "activates transcription of target genes.", "transcription of target genes. creb3l1", "target genes. creb3l1 creb3l2", "creb3l1 creb3l2 and", "creb3l2 and creb3l3 are", "and creb3l3 are activated by", "creb3l3 are activated by er", "are activated by er stress", "by er stress although", "er stress although the", "stress although the mechanisms", "although the mechanisms that cause", "the mechanisms that cause the", "mechanisms that cause the transit", "that cause the transit of", "cause the transit of the", "the transit of the creb3", "transit of the creb3 proteins", "of the creb3 proteins are", "the creb3 proteins are not", "creb3 proteins are not fully", "proteins are not fully characterized.", "are not fully characterized. unlike", "not fully characterized. unlike the", "fully characterized. unlike the atf6", "characterized. unlike the atf6 factors", "the atf6 factors creb3", "atf6 factors creb3 proteins", "factors creb3 proteins do", "creb3 proteins do not appear", "proteins do not appear to", "do not appear to interact", "not appear to interact with", "appear to interact with hspa5", "interact with hspa5 bip", "hspa5 bip and", "bip and therefore do", "and therefore do not appear", "therefore do not appear to", "do not appear to sense", "not appear to sense unfolded", "appear to sense unfolded proteins", "to sense unfolded proteins by", "sense unfolded proteins by dissociation", "unfolded proteins by dissociation of", "proteins by dissociation of hspa5", "by dissociation of hspa5 when", "dissociation of hspa5 when hspa5", "of hspa5 when hspa5 binds", "hspa5 when hspa5 binds the", "when hspa5 binds the unfolded", "hspa5 binds the unfolded proteins." ] }, { "record_id": "GLY_000594_1_1155", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8876493", "r hsa", "hsa 8876493", "r hsa 8876493" ] }, { "record_id": "GLY_000594_1_1155", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "inla mediated", "mediated entry", "entry of", "of listeria", "listeria monocytogenes", "monocytogenes into", "into host", "host cells", "inla mediated entry", "mediated entry of", "entry of listeria", "of listeria monocytogenes", "listeria monocytogenes into", "monocytogenes into host", "into host cells", "inla mediated entry of", "mediated entry of listeria", "entry of listeria monocytogenes", "of listeria monocytogenes into", "listeria monocytogenes into host", "monocytogenes 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"kinase and", "and phosphorylation", "phosphorylation of", "of cdh1", "cdh1 and", "and cdh1", "cdh1 bound", "bound beta", "beta catenin", "fujita et", "al. 2002", "mclachlan et", "al. 2007", "sousa et", "bonazzi et", "al. 2008", "2008 .", ". integrins", "integrins likely", "likely contribute", "contribute to", "cdh1 triggered", "triggered src", "src activation", "and erks", "mapk1 and", "and mapk3", "rocks and", "and mlck", "mlck may", "may also", "also be", "be involved", "avizienyte et", "al. 2004", "martinez rico", "rico et", "al. 2010", "2010 .", ". fak1", "a src", "src regulated", "regulated protein", "may contribute", "to src", "src mediated", "mediated regulation", "regulation of", "2002 .
              phosphorylation", ".
              phosphorylation of", "and ctnnb1", "ctnnb1 by", "by src", "src creates", "creates docking", "docking sites", "sites for", "for a", "a cbl", "cbl like", "like ubiquitin", "ubiquitin protein", "protein ligase", "ligase hakai", "cbll1 .", ". cbll1", "cbll1 ubiquitinates", "ubiquitinates src", "src phosphorylated", "phosphorylated cdh1", "ctnnb1 upon", "upon inla", "inla binding", "as well", "well as", "as in", "in the", "the context", "context of", "cdh1 mediated", "mediated cell", "thus triggering", "triggering cdh1", "cdh1 endocytosis", "mukherjee et", "al. 2012", "2012 .
              cbll1", ".
              cbll1 may", "also undergo", "undergo src", "mediated phosphorylation", "phosphorylation and", "and subsequent", "subsequent autoubiquitination", "2002 .
              both", ".
              both clathrin", "clathrin mediated", "mediated and", "and caveolin", "caveolin mediated", "mediated endocytosis", "endocytosis are", "are implicated", "implicated in", "the inla", "monocytogenes to", "to host", "veiga et", "2007 .", ". src", "of cortactin", "cortactin and", "and the", "the arp2/3", "arp2/3 complex", "complex involved", "involved in", "in actin", "actin polymerization", "polymerization is", "is implicated", "in cdh1", "endocytosis and", "and listeria", "monocytogenes internalization", "ren et", "al. 2009", "2009 .", "the pathogenic bacteria", "pathogenic bacteria listeria", "bacteria listeria monocytogenes", "listeria monocytogenes can", "monocytogenes can enter", "can enter host", "enter host cells", "host cells through", "cells through endocytosis", "through endocytosis triggered", "endocytosis triggered by", "triggered by binding", "by binding of", "binding of the", "of the bacterial", "the bacterial cell", "bacterial cell wall", "cell wall protein", "wall protein internalin", "internalin inla", "to the e", "the e cadherin", "cadherin cdh1", "cdh1 complex", "complex at the", "at the host", "the host cell", "host cell plasma", "cell plasma membrane", "membrane mengaud", "mengaud et al.", "et al. 1996", "1996 lecuit", "lecuit et al.", "et al. 1999", "al. 1999 .", "1999 . binding", ". binding of", "binding of inla", "of inla to", "inla to cdh1", "cdh1 similar", "similar to cdh1", "to cdh1 engagement", "cdh1 engagement during", "engagement during normal", "during normal cell", "normal cell to", "cell to cell", "to cell adhesion", "adhesion triggers", "triggers activation of", "activation of the", "of the src", "the src protein", "src protein tyrosine", "protein tyrosine kinase", "tyrosine kinase and", "kinase and phosphorylation", "and phosphorylation of", "phosphorylation of cdh1", "of cdh1 and", "cdh1 and cdh1", "and cdh1 bound", "cdh1 bound beta", "bound beta catenin", "catenin ctnnb1", "fujita et al.", "et al. 2002", "2002 mclachlan", "mclachlan et al.", "et al. 2007", "2007 sousa", "sousa et al.", "2007 bonazzi", "bonazzi et al.", "et al. 2008", "al. 2008 .", "2008 . integrins", ". integrins likely", "integrins likely contribute", "likely contribute to", "contribute to cdh1", "to cdh1 triggered", "cdh1 triggered src", "triggered src activation", "activation and", "erks mapk1", "mapk1 and mapk3", "rocks and mlck", "and mlck may", "mlck may also", "may also be", "also be involved", "involved avizienyte", "avizienyte et al.", "2002 avizienyte", "et al. 2004", "2004 martinez", "martinez rico et", "rico et al.", "et al. 2010", "al. 2010 .", "2010 . fak1", "fak1 ptk2", "a src regulated", "src regulated protein", "regulated protein tyrosine", "kinase may", "may contribute to", "contribute to src", "to src mediated", "src mediated regulation", "mediated regulation of", "regulation of cdh1", "cdh1 avizienyte", "al. 2002 .
              phosphorylation", "2002 .
              phosphorylation of", ".
              phosphorylation of cdh1", "cdh1 and ctnnb1", "and ctnnb1 by", "ctnnb1 by src", "by src creates", "src creates docking", "creates docking sites", "docking sites for", "sites for a", "for a cbl", "a cbl like", "cbl like ubiquitin", "like ubiquitin protein", "ubiquitin protein ligase", "protein ligase hakai", "hakai cbll1", "cbll1 . cbll1", ". cbll1 ubiquitinates", "cbll1 ubiquitinates src", "ubiquitinates src phosphorylated", "src phosphorylated cdh1", "phosphorylated cdh1 and", "and ctnnb1 upon", "ctnnb1 upon inla", "upon inla binding", "binding as", "as well as", "well as in", "as in the", "in the context", "the context of", "context of cdh1", "of cdh1 mediated", "cdh1 mediated cell", "mediated cell to", "adhesion thus", "thus triggering cdh1", "triggering cdh1 endocytosis", "endocytosis fujita", "2002 bonazzi", "2008 mukherjee", "mukherjee et al.", "et al. 2012", "al. 2012 .
              cbll1", "2012 .
              cbll1 may", ".
              cbll1 may also", "may also undergo", "also undergo src", "undergo src mediated", "src mediated phosphorylation", "mediated phosphorylation and", "phosphorylation and subsequent", "and subsequent autoubiquitination", "autoubiquitination fujita", "al. 2002 .
              both", "2002 .
              both clathrin", ".
              both clathrin mediated", "clathrin mediated and", "mediated and caveolin", "and caveolin mediated", "caveolin mediated endocytosis", "mediated endocytosis are", "endocytosis are implicated", "are implicated in", "implicated in the", "in the inla", "the inla mediated", "listeria monocytogenes to", "monocytogenes to host", "to host cells", "cells veiga", "veiga et al.", "al. 2007 .", "2007 . src", ". src mediated", "mediated phosphorylation of", "phosphorylation of cortactin", "of cortactin and", "cortactin and the", "and the arp2/3", "the arp2/3 complex", "arp2/3 complex involved", "complex involved in", "involved in actin", "in actin polymerization", "actin polymerization is", "polymerization is implicated", "is implicated in", "implicated in cdh1", "in cdh1 endocytosis", "cdh1 endocytosis and", "endocytosis and listeria", "and listeria monocytogenes", "listeria monocytogenes internalization", "internalization sousa", "2007 ren", "ren et al.", "et al. 2009", "al. 2009 .", "the pathogenic bacteria listeria", "pathogenic bacteria listeria monocytogenes", "bacteria listeria monocytogenes can", "listeria monocytogenes can enter", "monocytogenes can enter host", "can enter host cells", "enter host cells through", "host cells through endocytosis", "cells through endocytosis triggered", "through endocytosis triggered by", "endocytosis triggered by binding", "triggered by binding of", "by binding of the", "binding of the bacterial", "of the bacterial cell", "the bacterial cell wall", "bacterial cell wall protein", "cell wall protein internalin", "protein internalin inla", "inla to the", "to the e cadherin", "e cadherin cdh1", "cdh1 complex at", "complex at the host", "at the host cell", "the host cell plasma", "host cell plasma membrane", "plasma membrane mengaud", "membrane mengaud et", "mengaud et al. 1996", "al. 1996 lecuit", "1996 lecuit et", "lecuit et al. 1999", "et al. 1999 .", "al. 1999 . binding", "1999 . binding of", ". binding of inla", "binding of inla to", "of inla to cdh1", "to cdh1 similar", "cdh1 similar to", "similar to cdh1 engagement", "to cdh1 engagement during", "cdh1 engagement during normal", "engagement during normal cell", "during normal cell to", "normal cell to cell", "cell to cell adhesion", "cell adhesion triggers", "adhesion triggers activation", "triggers activation of the", "activation of the src", "of the src protein", "the src protein tyrosine", "src protein tyrosine kinase", "protein tyrosine kinase and", "tyrosine kinase and phosphorylation", "kinase and phosphorylation of", "and phosphorylation of cdh1", "phosphorylation of cdh1 and", "of cdh1 and cdh1", "cdh1 and cdh1 bound", "and cdh1 bound beta", "cdh1 bound beta catenin", "beta catenin ctnnb1", "ctnnb1 fujita", "fujita et al. 2002", "al. 2002 mclachlan", "2002 mclachlan et", "mclachlan et al. 2007", "al. 2007 sousa", "2007 sousa et", "sousa et al. 2007", "al. 2007 bonazzi", "2007 bonazzi et", "bonazzi et al. 2008", "et al. 2008 .", "al. 2008 . integrins", "2008 . integrins likely", ". integrins likely contribute", "integrins likely contribute to", "likely contribute to cdh1", "contribute to cdh1 triggered", "to cdh1 triggered src", "cdh1 triggered src activation", "src activation and", "activation and erks", "and erks mapk1", "erks mapk1 and", "mapk3 rocks", "rocks and mlck may", "and mlck may also", "mlck may also be", "may also be involved", "be involved avizienyte", "involved avizienyte et", "avizienyte et al. 2002", "al. 2002 avizienyte", "2002 avizienyte et", "avizienyte et al. 2004", "al. 2004 martinez", "2004 martinez rico", "martinez rico et al.", "rico et al. 2010", "et al. 2010 .", "al. 2010 . fak1", ". fak1 ptk2", "ptk2 a", "a src regulated protein", "src regulated protein tyrosine", "regulated protein tyrosine kinase", "tyrosine kinase may", "kinase may contribute", "may contribute to src", "contribute to src mediated", "to src mediated regulation", "src mediated regulation of", "mediated regulation of cdh1", "of cdh1 avizienyte", "cdh1 avizienyte et", "et al. 2002 .
              phosphorylation", "al. 2002 .
              phosphorylation of", "2002 .
              phosphorylation of cdh1", ".
              phosphorylation of cdh1 and", "of cdh1 and ctnnb1", "cdh1 and ctnnb1 by", "and ctnnb1 by src", "ctnnb1 by src creates", "by src creates docking", "src creates docking sites", "creates docking sites for", "docking sites for a", "sites for a cbl", "for a cbl like", "a cbl like ubiquitin", "cbl like ubiquitin protein", "like ubiquitin protein ligase", "ubiquitin protein ligase hakai", "ligase hakai cbll1", "hakai cbll1 .", "cbll1 . cbll1 ubiquitinates", ". cbll1 ubiquitinates src", "cbll1 ubiquitinates src phosphorylated", "ubiquitinates src phosphorylated cdh1", "src phosphorylated cdh1 and", "phosphorylated cdh1 and ctnnb1", "cdh1 and ctnnb1 upon", "and ctnnb1 upon inla", "ctnnb1 upon inla binding", "inla binding as", "binding as well", "as well as in", "well as in the", "as in the context", "in the context of", "the context of cdh1", "context of cdh1 mediated", "of cdh1 mediated cell", "cdh1 mediated cell to", "mediated cell to cell", "cell adhesion thus", "adhesion thus triggering", "thus triggering cdh1 endocytosis", "cdh1 endocytosis fujita", "endocytosis fujita et", "al. 2002 bonazzi", "2002 bonazzi et", "al. 2008 mukherjee", "2008 mukherjee et", "mukherjee et al. 2012", "et al. 2012 .
              cbll1", "al. 2012 .
              cbll1 may", "2012 .
              cbll1 may also", ".
              cbll1 may also undergo", "may also undergo src", "also undergo src mediated", "undergo src mediated phosphorylation", "src mediated phosphorylation and", "mediated phosphorylation and subsequent", "phosphorylation and subsequent autoubiquitination", "subsequent autoubiquitination fujita", "autoubiquitination fujita et", "et al. 2002 .
              both", "al. 2002 .
              both clathrin", "2002 .
              both clathrin mediated", ".
              both clathrin mediated and", "clathrin mediated and caveolin", "mediated and caveolin mediated", "and caveolin mediated endocytosis", "caveolin mediated endocytosis are", "mediated endocytosis are implicated", "endocytosis are implicated in", "are implicated in the", "implicated in the inla", "in the inla mediated", "the inla mediated entry", "of listeria monocytogenes to", "listeria monocytogenes to host", "monocytogenes to host cells", "host cells veiga", "cells veiga et", "veiga et al. 2007", "et al. 2007 .", "al. 2007 . src", "2007 . src mediated", ". src mediated phosphorylation", "src mediated phosphorylation of", "mediated phosphorylation of cortactin", "phosphorylation of cortactin and", "of cortactin and the", "cortactin and the arp2/3", "and the arp2/3 complex", "the arp2/3 complex involved", "arp2/3 complex involved in", "complex involved in actin", "involved in actin polymerization", "in actin polymerization is", "actin polymerization is implicated", "polymerization is implicated in", "is implicated in cdh1", "implicated in cdh1 endocytosis", "in cdh1 endocytosis and", "cdh1 endocytosis and listeria", "endocytosis and listeria monocytogenes", "and listeria monocytogenes internalization", "monocytogenes internalization sousa", "internalization sousa et", "al. 2007 ren", "2007 ren et", "ren et al. 2009", "et al. 2009 .", "the pathogenic bacteria listeria monocytogenes", "pathogenic bacteria listeria monocytogenes can", "bacteria listeria monocytogenes can enter", "listeria monocytogenes can enter host", "monocytogenes can enter host cells", "can enter host cells through", "enter host cells through endocytosis", "host cells through endocytosis triggered", "cells through endocytosis triggered by", "through endocytosis triggered by binding", "endocytosis triggered by binding of", "triggered by binding of the", "by binding of the bacterial", "binding of the bacterial cell", "of the bacterial cell wall", "the bacterial cell wall protein", "bacterial cell wall protein internalin", "wall protein internalin inla", "internalin inla to", "inla to the e", "the e cadherin cdh1", "cadherin cdh1 complex", "cdh1 complex at the", "complex at the host cell", "at the host cell plasma", "the host cell plasma membrane", "cell plasma membrane mengaud", "plasma membrane mengaud et", "membrane mengaud et al.", "et al. 1996 lecuit", "al. 1996 lecuit et", "1996 lecuit et al.", "lecuit et al. 1999 .", "et al. 1999 . binding", "al. 1999 . binding of", "1999 . binding of inla", ". binding of inla to", "binding of inla to cdh1", "inla to cdh1 similar", "to cdh1 similar to", "cdh1 similar to cdh1", "similar to cdh1 engagement during", "to cdh1 engagement during normal", "cdh1 engagement during normal cell", "engagement during normal cell to", "during normal cell to cell", "normal cell to cell adhesion", "to cell adhesion triggers", "cell adhesion triggers activation", "adhesion triggers activation of", "triggers activation of the src", "activation of the src protein", "of the src protein tyrosine", "the src protein tyrosine kinase", "src protein tyrosine kinase and", "protein tyrosine kinase and phosphorylation", "tyrosine kinase and phosphorylation of", "kinase and phosphorylation of cdh1", "and phosphorylation of cdh1 and", "phosphorylation of cdh1 and cdh1", "of cdh1 and cdh1 bound", "cdh1 and cdh1 bound beta", "and cdh1 bound beta catenin", "bound beta catenin ctnnb1", "ctnnb1 fujita et", "et al. 2002 mclachlan", "al. 2002 mclachlan et", "2002 mclachlan et al.", "et al. 2007 sousa", "al. 2007 sousa et", "2007 sousa et al.", "et al. 2007 bonazzi", "al. 2007 bonazzi et", "2007 bonazzi et al.", "bonazzi et al. 2008 .", "et al. 2008 . integrins", "al. 2008 . integrins likely", "2008 . integrins likely contribute", ". integrins likely contribute to", "integrins likely contribute to cdh1", "likely contribute to cdh1 triggered", "contribute to cdh1 triggered src", "to cdh1 triggered src activation", "triggered src activation and", "src activation and erks", "and erks mapk1 and", "erks mapk1 and mapk3", "and mapk3 rocks", "mapk3 rocks and", "rocks and mlck may also", "and mlck may also be", "mlck may also be involved", "also be involved avizienyte", "be involved avizienyte et", "involved avizienyte et al.", "et al. 2002 avizienyte", "al. 2002 avizienyte et", "2002 avizienyte et al.", "et al. 2004 martinez", "al. 2004 martinez rico", "2004 martinez rico et", "martinez rico et al. 2010", "rico et al. 2010 .", "et al. 2010 . fak1", "2010 . fak1 ptk2", "ptk2 a src", "a src regulated protein tyrosine", "src regulated protein tyrosine kinase", "protein tyrosine kinase may", "tyrosine kinase may contribute", "kinase may contribute to", "may contribute to src mediated", "contribute to src mediated regulation", "to src mediated regulation of", "src mediated regulation of cdh1", "regulation of cdh1 avizienyte", "of cdh1 avizienyte et", "cdh1 avizienyte et al.", "avizienyte et al. 2002 .
              phosphorylation", "et al. 2002 .
              phosphorylation of", "al. 2002 .
              phosphorylation of cdh1", "2002 .
              phosphorylation of cdh1 and", ".
              phosphorylation of cdh1 and ctnnb1", "of cdh1 and ctnnb1 by", "cdh1 and ctnnb1 by src", "and ctnnb1 by src creates", "ctnnb1 by src creates docking", "by src creates docking sites", "src creates docking sites for", "creates docking sites for a", "docking sites for a cbl", "sites for a cbl like", "for a cbl like ubiquitin", "a cbl like ubiquitin protein", "cbl like ubiquitin protein ligase", "like ubiquitin protein ligase hakai", "protein ligase hakai cbll1", "ligase hakai cbll1 .", "hakai cbll1 . cbll1", "cbll1 . cbll1 ubiquitinates src", ". cbll1 ubiquitinates src phosphorylated", "cbll1 ubiquitinates src phosphorylated cdh1", "ubiquitinates src phosphorylated cdh1 and", "src phosphorylated cdh1 and ctnnb1", "phosphorylated cdh1 and ctnnb1 upon", "cdh1 and ctnnb1 upon inla", "and ctnnb1 upon inla binding", "upon inla binding as", "inla binding as well", "binding as well as", "as well as in the", "well as in the context", "as in the context of", "in the context of cdh1", "the context of cdh1 mediated", "context of cdh1 mediated cell", "of cdh1 mediated cell to", "cdh1 mediated cell to cell", "mediated cell to cell adhesion", "to cell adhesion thus", "cell adhesion thus triggering", "adhesion thus triggering cdh1", "triggering cdh1 endocytosis fujita", "cdh1 endocytosis fujita et", "endocytosis fujita et al.", "et al. 2002 bonazzi", "al. 2002 bonazzi et", "2002 bonazzi et al.", "et al. 2008 mukherjee", "al. 2008 mukherjee et", "2008 mukherjee et al.", "mukherjee et al. 2012 .
              cbll1", "et al. 2012 .
              cbll1 may", "al. 2012 .
              cbll1 may also", "2012 .
              cbll1 may also undergo", ".
              cbll1 may also undergo src", "may also undergo src mediated", "also undergo src mediated phosphorylation", "undergo src mediated phosphorylation and", "src mediated phosphorylation and subsequent", "mediated phosphorylation and subsequent autoubiquitination", "and subsequent autoubiquitination fujita", "subsequent autoubiquitination fujita et", "autoubiquitination fujita et al.", "fujita et al. 2002 .
              both", "et al. 2002 .
              both clathrin", "al. 2002 .
              both clathrin mediated", "2002 .
              both clathrin mediated and", ".
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senses signals from red", "senses signals from red blood", "signals from red blood cell", "from red blood cell differentiation", "red blood cell differentiation is", "blood cell differentiation is unclear.", "cell differentiation is unclear. phosphorylation", "differentiation is unclear. phosphorylation of", "is unclear. phosphorylation of serine", "unclear. phosphorylation of serine residues", "phosphorylation of serine residues 17", "of serine residues 17 and", "serine residues 17 and 24", "residues 17 and 24 flanking", "17 and 24 flanking the", "and 24 flanking the bnip3", "24 flanking the bnip3 lir", "flanking the bnip3 lir promotes", "the bnip3 lir promotes binding", "bnip3 lir promotes binding to", "lir promotes binding to specific", "promotes binding to specific lc3", "binding to specific lc3 family", "to specific lc3 family members", "specific lc3 family members lc3b", "lc3 family members lc3b and", "family members lc3b and gate", "members lc3b and gate 16", "lc3b and gate 16 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              the itgbl1 gene", ".
              the itgbl1 gene encodes", "itgbl1 gene encodes integrin", "gene encodes integrin beta", "encodes integrin beta like", "integrin beta like protein", "beta like protein 1", "protein 1 which", "1 which is", "which is implicated in", "is implicated in regulation", "implicated in regulation of", "in regulation of tgf", "regulation of tgf beta", "of tgf beta signaling", "tgf beta signaling and", "beta signaling and runx2", "signaling and runx2 induced", "and runx2 induced bone", "runx2 induced bone metastasis", "induced bone metastasis of", "breast cancer li", "cancer li et", "li et al. 2015", "et al. 2015 .
              runx2", "al. 2015 .
              runx2 mediated", "2015 .
              runx2 mediated transcription", ".
              runx2 mediated transcription of", "mediated transcription of the", "transcription of the mmp13", "of the mmp13 gene", "mmp13 gene encoding", "gene encoding colagenase", "colagenase 3 matrix", "3 matrix metalloproteinase", "13 is", "is stimulated by akt", "stimulated by akt mediated", "by akt mediated phosphorylation", "akt mediated phosphorylation of", "mediated phosphorylation of runx2", "phosphorylation of runx2 and", "of runx2 and is", "runx2 and is implicated", "and is implicated in", "is implicated in invasiveness", "implicated in invasiveness of", "in invasiveness of breast", "invasiveness of breast cancer", "cancer cells pande", "cells pande et", "pande et al. 2013", "et al. 2013 .", "al. 2013 . mmp13", "2013 . mmp13 is", ". mmp13 is involved", "mmp13 is involved in", "is involved in migration", "involved in migration of", "in migration of innate", "migration of innate immune", "of innate immune system", "innate immune system cells", "immune system cells in", "system cells in response", "cells in response to", "in response to injury", "to injury zhang", "injury zhang et", "zhang et al. 2008", "al. 2008 and", "2008 and in", "and in remodelling of", "in remodelling of skeletal", "remodelling of skeletal tissues", "skeletal tissues ortega", "tissues ortega et", "ortega et al. 2003", "et al. 2003 .
              ", "runx2 regulates expression of several", "regulates expression of several genes", "expression of several genes implicated", "of several genes implicated in", "several genes implicated in cell", "genes implicated in cell migration", "implicated in cell migration during", "in cell migration during normal", "cell migration during normal development", "migration during normal development and", "during normal development and bone", "normal development and bone metastasis", "development and bone metastasis of", "and bone metastasis of breast", "bone metastasis of breast cancer", "metastasis of breast cancer cells.
              runx2", "of breast cancer cells.
              runx2 stimulates", "breast cancer cells.
              runx2 stimulates transcription", "cancer cells.
              runx2 stimulates transcription of", "cells.
              runx2 stimulates transcription of the", "stimulates transcription of the itga5", "transcription of the itga5 gene", "the itga5 gene encoding", "itga5 gene encoding integrin", "gene encoding integrin alpha", "encoding integrin alpha 5. integrin", "integrin alpha 5. integrin alpha", "alpha 5. integrin alpha 5", "5. integrin alpha 5 promotes", "integrin alpha 5 promotes adhesion", "alpha 5 promotes adhesion of", "5 promotes adhesion of breast", "promotes adhesion of breast cancer", "adhesion of breast cancer cells", "of breast cancer cells to", "breast cancer cells to the", "cancer cells to the bone", "to the bone thus", "the bone thus facilitating", "bone thus facilitating formation", "thus facilitating formation of bone", "facilitating formation of bone metastases", "of bone metastases li", "bone metastases li et", "metastases li et al.", "li et al. 2016 .", "et al. 2016 . itga5", "al. 2016 . itga5 is", "2016 . itga5 is implicated", ". itga5 is implicated in", "itga5 is implicated in migration", "is implicated in migration of", "implicated in migration of human", "in migration of human dental", "migration of human dental pulp", "of human dental pulp stem", "human dental pulp stem cells", "pulp stem cells xu", "stem cells xu et", "cells xu et al.", "xu et al. 2015 .", "et al. 2015 . in", "al. 2015 . in zebrafish", ". in zebrafish integrin", "in zebrafish integrin alpha", "zebrafish integrin alpha 5", "integrin alpha 5 coordinates cell", "alpha 5 coordinates cell migration", "5 coordinates cell migration during", "coordinates cell migration during development", "cell migration during development of", "migration during development of sensory", "during development of sensory organs", "of sensory organs bhat", "sensory organs bhat et", "organs bhat et al.", "bhat et al. 2011 .", "et al. 2011 . during", "al. 2011 . during mouse", "2011 . during mouse retinal", ". during mouse retinal angiogenesis", "mouse retinal angiogenesis integrin", "retinal angiogenesis integrin alpha", "angiogenesis integrin alpha 5", "integrin alpha 5 regulates migration", "alpha 5 regulates migration of", "5 regulates migration of endothelial", "regulates migration of endothelial cells", "of endothelial cells stenzel", "endothelial cells stenzel et", "cells stenzel et al.", "stenzel et al. 2011 .
              the", "et al. 2011 .
              the itgbl1", "al. 2011 .
              the itgbl1 gene", "2011 .
              the itgbl1 gene encodes", ".
              the itgbl1 gene encodes integrin", "itgbl1 gene encodes integrin beta", "gene encodes integrin beta like", "encodes integrin beta like protein", "integrin beta like protein 1", "like protein 1 which", "protein 1 which is", "1 which is implicated", "which is implicated in regulation", "is implicated in regulation of", "implicated in regulation of tgf", "in regulation of tgf beta", "regulation of tgf beta signaling", "of tgf beta signaling and", "tgf beta signaling and runx2", "beta signaling and runx2 induced", "signaling and runx2 induced bone", "and runx2 induced bone metastasis", "runx2 induced bone metastasis of", "induced bone metastasis of breast", "of breast cancer li", "breast cancer li et", "cancer li et al.", "li et al. 2015 .
              runx2", "et al. 2015 .
              runx2 mediated", "al. 2015 .
              runx2 mediated transcription", "2015 .
              runx2 mediated transcription of", ".
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              " ] }, { "record_id": "GLY_000594_1_1162", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8941855", "r hsa", "hsa 8941855", "r hsa 8941855" ] }, { "record_id": "GLY_000594_1_1162", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "runx3 regulates", "regulates cdkn1a", "cdkn1a transcription", "runx3 regulates cdkn1a", "regulates cdkn1a transcription", "runx3 regulates cdkn1a transcription", "runx3 contributes", "contributes to", "to the", "the upregulation", "upregulation of", "of the", "the cdkn1a", "gene transcription", "transcription in", "in response", "response to", "to tgf", "tgf beta", "signaling. runx3", "runx3 binds", "binds to", "to smad3", "smad3 and", "and smad4", "and cooperates", "cooperates with", "with the", "the activated", "activated smad3:smad4", "smad3:smad4 complex", "complex in", "in transactivation", "transactivation of", "of cdkn1a.", "cdkn1a. runx3", "runx3 knockout", "knockout mice", "mice exhibit", "exhibit decreased", "decreased sensitivity", "sensitivity to", "beta and", "and develop", "develop gastric", "gastric epithelial", "epithelial hyperplasia", "chi et", "et al.", "al. 2005", "2005 .", ". in", "beta signaling", "the cbfb:runx3", "cbfb:runx3 complex", "complex binds", "the tumor", "tumor suppressor", "suppressor zfhx3", "through an", "an unknown", "unknown mechanism", "this complex", "complex positively", "positively regulates", "regulates the", "mabuchi et", "al. 2010", "2010 .
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              efflux", ".
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"membrane at the bases of", "at the bases of cristae.", "the bases of cristae. micos", "bases of cristae. micos also", "of cristae. micos also links", "cristae. micos also links these", "micos also links these regions", "also links these regions of", "links these regions of the", "these regions of the inner", "regions of the inner membrane", "of the inner membrane with", "the inner membrane with complexes", "membrane with complexes the", "with complexes the sam", "complexes the sam complex", "sam complex and in", "complex and in fungi", "in fungi the tom", "fungi the tom complex", "the tom complex embedded", "tom complex embedded in", "complex embedded in the", "embedded in the outer membrane.", "in the outer membrane. chchd3", "outer membrane. chchd3 mic19", "chchd3 mic19 and", "immt mic60 subunits", "mic60 subunits of micos", "subunits of micos also interact", "of micos also interact with", "micos also interact with opa1", "also interact with opa1 at", "interact with opa1 at the", 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              formation", "et al. 2016 .
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atp", "micos or f1fo atp synthase", "or f1fo atp synthase oligomerization", "f1fo atp synthase oligomerization produce", "atp synthase oligomerization produce abnormal", "synthase oligomerization produce abnormal mitochondrial", "oligomerization produce abnormal mitochondrial morphologies." ] }, { "record_id": "GLY_000594_1_1166", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8949664", "r hsa", "hsa 8949664", "r hsa 8949664" ] }, { "record_id": "GLY_000594_1_1166", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "processing of", "of smdt1", "processing of smdt1", "proteolytic processing", "of prosmdt1", "regulates assembly", "assembly of", "of properly", "properly regulated", "regulated mitochondrial", "mitochondrial calcium", "calcium uniporter", "konig et", "et al.", "al. 2016", "2016 .", ". c2orf47", "in a", "a complex", "complex with", "with afg3l2", "m aaa", "aaa protease", "binds the", 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accumulation of tyrosine", "accumulation of tyrosine tyrosinemia", "tyrosinemia mitchell et", "et al. 2001 held", "2001 held 2006" ] }, { "record_id": "GLY_000594_1_1171", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8963693", "r hsa", "hsa 8963693", "r hsa 8963693" ] }, { "record_id": "GLY_000594_1_1171", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "aspartate and", "and asparagine", "asparagine metabolism", "aspartate and asparagine", "and asparagine metabolism", "aspartate and asparagine metabolism", "these reactions", "reactions mediate", "mediate the", "the synthesis", "synthesis of", "of aspartate", "asparagine from", "from glutamate", "tca cycle", "cycle intermediates", "and ammonia", "ammonia and", "and and", "and allow", "allow the", "the utilization", "utilization of", "of carbon", "carbon atoms", "atoms from", "from these", "these amino", "amino acids", "acids for", "for 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              expression", ".
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              maturation", ".
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              lpl", "lipoprotein particles.
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              expression", "2011 .
              expression of", ".
              expression of the", "of the lpl", "the lpl gene", "lpl gene is", "gene is transcriptionally", "is transcriptionally regulated", "transcriptionally regulated by", "regulated by cyclic", "by cyclic amp", "cyclic amp responsive", "amp responsive element", "responsive element binding", "element binding protein", "binding protein 3", "protein 3 like", "3 like protein", "like protein 3", "3 creb3l3", "which also regulates", "also regulates the", "regulates the expression", "the expression of", "expression of apoa4", "apoa4 apoa5", "apoa5 apoc2", "apoc2 cidec", "cidec and fgf21", "fgf21 lee", "lee et al.", "al. 2011 .
              maturation", "2011 .
              maturation of", ".
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              lpl", "circulating lipoprotein particles.
              lpl is", "lipoprotein particles.
              lpl is widely", "particles.
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              expression", "al. 2011 .
              expression of", "2011 .
              expression of the", ".
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              maturation", "al. 2011 .
              maturation of", "2011 .
              maturation of lipc", ".
              maturation of lipc enzyme", "of lipc enzyme requires", "lipc enzyme requires association", "enzyme requires association with", "requires association with lmf1", "association with lmf1 protein", "lmf1 protein or", "protein or possibly", "or possibly inferred", "possibly inferred from", "inferred from sequence similarity", "sequence similarity lmf2", "similarity lmf2 .", "lmf2 . heparin binding", ". heparin binding stabilizes", "heparin binding stabilizes lipc", "binding stabilizes lipc in", "stabilizes lipc in its", "lipc in its active", "in its active dimeric", "its active dimeric form", "dimeric form babilonia", "form babilonia rosa", "babilonia rosa & neher", "rosa & neher 2014", "& neher 2014 .", "lipase lpl and", "lpl and hepatic triacylglycerol", "hepatic triacylglycerol lipase lipc", "lipase lipc enzymes", "lipc enzymes on the", "enzymes on the lumenal surfaces", "on the lumenal surfaces of", "the lumenal surfaces of capillary", "lumenal surfaces of capillary endothelia", "surfaces of capillary endothelia mediate", "of capillary endothelia mediate the", "capillary endothelia mediate the hydrolysis", "endothelia mediate the hydrolysis of", "mediate the hydrolysis of triglyceride", "the hydrolysis of triglyceride molecules", "hydrolysis of triglyceride molecules in", "of triglyceride molecules in circulating", "triglyceride molecules in circulating lipoprotein", "molecules in circulating lipoprotein particles.
              lpl", "in circulating lipoprotein particles.
              lpl is", "circulating lipoprotein particles.
              lpl is widely", "lipoprotein particles.
              lpl is widely expressed", "particles.
              lpl is widely expressed in", "is widely expressed in the", "widely expressed in the body", "expressed in the body and", "in the body and is", "the body and is especially", "body and is especially abundant", "and is especially abundant in", "is especially abundant in adipocytes", "especially abundant in adipocytes and", "abundant in adipocytes and skeletal", "in adipocytes and skeletal and", "adipocytes and skeletal and cardiac", "and skeletal and cardiac myocytes.", "skeletal and cardiac myocytes. activation", "and cardiac myocytes. activation of", "cardiac myocytes. activation of the", "myocytes. activation of the protein", "activation of the protein requires", "of the protein requires glycosylation", "protein requires glycosylation dimerization", "glycosylation dimerization and", "dimerization and glycosylphosphatidylinositol anchored", "and glycosylphosphatidylinositol anchored high density", "glycosylphosphatidylinositol anchored high density lipoprotein", "anchored high density lipoprotein binding", "high density lipoprotein binding protein", "density lipoprotein binding protein 1", "binding protein 1 gpihbp1", "gpihbp1 which delivers", "which delivers it to heparan", "delivers it to heparan sulfate", "it to heparan sulfate proteoglycan", "heparan sulfate proteoglycan hspg", "proteoglycan hspg associated", "hspg associated with the", "associated with the plasma membrane.", "with the plasma membrane. it", "the plasma membrane. it is", "plasma membrane. it is inactivated", "membrane. it is inactivated by", "it is inactivated by proteolytic", "is inactivated by proteolytic cleavage", "by proteolytic cleavage berryman", "proteolytic cleavage berryman &", "cleavage berryman & bensadoun", "& bensadoun 1995 sukonina", "bensadoun 1995 sukonina et", "1995 sukonina et al.", "et al. 2006 young", "al. 2006 young et", "2006 young et al.", "young et al. 2011 .
              expression", "et al. 2011 .
              expression of", "al. 2011 .
              expression of the", "2011 .
              expression of the lpl", ".
              expression of the lpl gene", "of the lpl gene is", "the lpl gene is transcriptionally", "lpl gene is transcriptionally regulated", "gene is transcriptionally regulated by", "is transcriptionally regulated by cyclic", "transcriptionally regulated by cyclic amp", "regulated by cyclic amp responsive", "by cyclic amp responsive element", "cyclic amp responsive element binding", "amp responsive element binding protein", "responsive element binding protein 3", "element binding protein 3 like", "binding protein 3 like protein", "protein 3 like protein 3", "like protein 3 creb3l3", "creb3l3 which also", "which also regulates the expression", "also regulates the expression of", "regulates the expression of apoa4", "expression of apoa4 apoa5", "apoa4 apoa5 apoc2", "apoa5 apoc2 cidec", "apoc2 cidec and fgf21", "cidec and fgf21 lee", "and fgf21 lee et", "fgf21 lee et al.", "lee et al. 2011 .
              maturation", "et al. 2011 .
              maturation of", "al. 2011 .
              maturation of lipc", "2011 .
              maturation of lipc enzyme", ".
              maturation of lipc enzyme requires", "of lipc enzyme requires association", "lipc enzyme requires association with", "enzyme requires association with lmf1", "requires association with lmf1 protein", "with lmf1 protein or", "lmf1 protein or possibly", "or possibly inferred from", "possibly inferred from sequence", "from sequence similarity lmf2", "sequence similarity lmf2 .", "similarity lmf2 . heparin", "lmf2 . heparin binding stabilizes", ". heparin binding stabilizes lipc", "heparin binding stabilizes lipc in", "binding stabilizes lipc in its", "stabilizes lipc in its active", "lipc in its active dimeric", "in its active dimeric form", "active dimeric form babilonia", "dimeric form babilonia rosa", "form babilonia rosa &", "babilonia rosa & neher 2014", "rosa & neher 2014 ." ] }, { "record_id": "GLY_000594_1_1174", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8963896", "r hsa", "hsa 8963896", "r hsa 8963896" ] }, { "record_id": "GLY_000594_1_1174", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hdl assembly", "hdl particles", "particles play", "play a", "a central", "central role", "role in", "in the", "the reverse", "reverse transport", "transport of", "of cholesterol", "the process", "process by", "by which", "which cholesterol", "cholesterol in", "in tissues", "tissues other", "other than", "than the", "the liver", "liver is", "is returned", "returned to", "to the", "liver for", "for conversion", "conversion to", "to bile", "bile salts", "salts and", "and excretion", "excretion from", "from the", "the body", "body and", "and provided", "provided to", "to tissues", "tissues such", "such as", "as the", "the adrenals", "adrenals and", "and gonads", "gonads for", "for steroid", "steroid hormone", "hormone synthesis", "tall et", "et al.", "al. 2008", "2008 .
              hdl", ".
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              hdl", "2008 .
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              hdl", "al. 2008 .
              hdl particles", "2008 .
              hdl particles are", ".
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              here", "re used.
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              hdl", "et al. 2008 .
              hdl particles", "al. 2008 .
              hdl particles are", "2008 .
              hdl particles are heterogeneous", ".
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"with cells carrying excess cholesterol", "carrying excess cholesterol transformation", "excess cholesterol transformation to", "cholesterol transformation to spherical", "to spherical hdl are", "spherical hdl are annotated." ] }, { "record_id": "GLY_000594_1_1175", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8963901", "r hsa", "hsa 8963901", "r hsa 8963901" ] }, { "record_id": "GLY_000594_1_1175", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "chylomicron remodeling", "as chylomicrons", "chylomicrons circulate", "circulate in", "in the", "the body", "they acquire", "acquire molecules", "molecules of", "of apolipoproteins", "apolipoproteins c", "c and", "and e", "and through", "through interaction", "interaction with", "with endothelial", "endothelial lipases", "lipases can", "can lose", "lose a", "a large", "large fraction", "fraction of", "of their", "their triacylglycerol.", 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              at the hdl", "the hdl surface", "surface lcat", "lcat lecithin", "lecithin cholesterol acyltransferase", "acyltransferase associates", "associates strongly with", "strongly with hdl", "with hdl particles", "hdl particles and", "and activated", "activated by apoa", "by apoa i", "i catalyzes", "catalyzes the reaction", "the reaction of", "reaction of cholesterol", "of cholesterol and", "cholesterol and phosphatidylcholine", "and phosphatidylcholine to", "phosphatidylcholine to yield", "to yield cholesterol", "yield cholesterol esterified", "cholesterol esterified with", "esterified with a", "with a long", "a long chain", "long chain fatty", "chain fatty acid", "fatty acid and", "acid and 2", "and 2 lysophosphatidylcholine.", "2 lysophosphatidylcholine. the", "lysophosphatidylcholine. the hydrophobic", "the hydrophobic cholesterol", "hydrophobic cholesterol ester", "cholesterol ester reaction", "ester reaction product", "reaction product is", "product is strongly", "is strongly associated", "strongly associated with", "associated with the", "with the hdl", "the hdl particle", "hdl particle while", "particle while the", "while the 2", "the 2 lysophosphatidylcholine", "2 lysophosphatidylcholine product", "lysophosphatidylcholine product is", "product is released.", "is released. torcetrapib", "released. torcetrapib associates", "torcetrapib associates with", "associates with a", "with a molecule", "a molecule of", "molecule of cetp", "of cetp and", "cetp and a", "and a spherical", "a spherical hdl", "spherical hdl particle", "hdl particle to", "particle to form", "to form a", "form a stable", "a stable complex", "complex thus", "thus trapping cetp", "trapping cetp and", "cetp and inhibiting", "and inhibiting cetp", "inhibiting cetp mediated", "cetp mediated lipid", "mediated lipid transfer", "lipid transfer between", "transfer between hdl", "between hdl and", "hdl and ldl", "ldl clark", "clark et al.", "et al. 2006", "al. 2006 .
              spherical", "2006 .
              spherical hdl", ".
              spherical hdl particles", "particles can bind", "can bind apoc", "bind apoc ii", "ii apoc", "apoc iii and", "iii and and", "and and apoe", "and apoe proteins.", "hdl high density", "density lipoprotein particles", "lipoprotein particles play", "particles play a central", "play a central role", "a central role in", "central role in the", "role in the reverse", "in the reverse transport", "the reverse transport of", "reverse transport of cholesterol", "of cholesterol the", "cholesterol the process", "the process by which", "process by which cholesterol", "by which cholesterol in", "which cholesterol in tissues", "cholesterol in tissues other", "in tissues other than", "tissues other than the", "other than the liver", "than the liver is", "the liver is returned", "liver is returned to", "is returned to the", "returned to the liver", "to the liver for", "the liver for conversion", "liver for conversion to", "for conversion to bile", "conversion to bile salts", "to bile salts and", "bile salts and excretion", "salts and excretion from", "and excretion from the", "excretion from the body", "from the body and", "the body and provided", "body and provided to", "and provided to tissues", "provided to tissues such", "to tissues such as", "tissues such as the", "such as the adrenals", "as the adrenals and", "the adrenals and gonads", "adrenals and gonads for", "and gonads for steroid", "gonads for steroid hormone", "for steroid hormone synthesis", "hormone synthesis tall", "synthesis tall et", "tall et al. 2008", "et al. 2008 .
              abcg1", "al. 2008 .
              abcg1 mediates", "2008 .
              abcg1 mediates the", ".
              abcg1 mediates the movement", "mediates the movement of", "the movement of intracellular", "movement of intracellular cholesterol", "of intracellular cholesterol to", "intracellular cholesterol to the", "cholesterol to the extracellular", "to the extracellular face", "the extracellular face of", "extracellular face of the", "face of the plasma", "of the plasma membrane", "the plasma membrane where", "plasma membrane where it", "membrane where it is", "where it is accessible", "it is accessible to", "is accessible to circulating", "accessible to circulating hdl", "circulating hdl vaughan", "hdl vaughan &", "vaughan & oram 2005", "& oram 2005 .", "oram 2005 . spherical", ". spherical mature", "mature hdl particles", "hdl particles can acquire", "particles can acquire additional", "can acquire additional molecules", "acquire additional molecules of", "additional molecules of free", "molecules of free cholesterol", "free cholesterol chol", "chol and phospholipid", "and phospholipid pl", "pl from cell", "from cell membranes.
              at the", "cell membranes.
              at the hdl", "membranes.
              at the hdl surface", "hdl surface lcat", "lcat lecithin cholesterol", "cholesterol acyltransferase associates", "acyltransferase associates strongly", "associates strongly with hdl", "strongly with hdl particles", "with hdl particles and", "particles and activated", "and activated by", "activated by apoa i", "apoa i catalyzes", "i catalyzes the", "catalyzes the reaction of", "the reaction of cholesterol", "reaction of cholesterol and", "of cholesterol and phosphatidylcholine", "cholesterol and phosphatidylcholine to", "and phosphatidylcholine to yield", "phosphatidylcholine to yield cholesterol", "to yield cholesterol esterified", "yield cholesterol esterified with", "cholesterol esterified with a", "esterified with a long", "with a long chain", "a long chain fatty", "long chain fatty acid", "chain fatty acid and", "fatty acid and 2", "acid and 2 lysophosphatidylcholine.", "and 2 lysophosphatidylcholine. the", "2 lysophosphatidylcholine. the hydrophobic", "lysophosphatidylcholine. the hydrophobic cholesterol", "the hydrophobic cholesterol ester", "hydrophobic cholesterol ester reaction", "cholesterol ester reaction product", "ester reaction product is", "reaction product is strongly", "product is strongly associated", "is strongly associated with", "strongly associated with the", "associated with the hdl", "with the hdl particle", "the hdl particle while", "hdl particle while the", "particle while the 2", "while the 2 lysophosphatidylcholine", "the 2 lysophosphatidylcholine product", "2 lysophosphatidylcholine product is", "lysophosphatidylcholine product is released.", "product is released. torcetrapib", "is released. torcetrapib associates", "released. torcetrapib associates with", "torcetrapib associates with a", "associates with a molecule", "with a molecule of", "a molecule of cetp", "molecule of cetp and", "of cetp and a", "cetp and a spherical", "and a spherical hdl", "a spherical hdl particle", "spherical hdl particle to", "hdl particle to form", "particle to form a", "to form a stable", "form a stable complex", "stable complex thus", "complex thus trapping", "thus trapping cetp and", "trapping cetp and inhibiting", "cetp and inhibiting cetp", "and inhibiting cetp mediated", "inhibiting cetp mediated lipid", "cetp mediated lipid transfer", "mediated lipid transfer between", "lipid transfer between hdl", "transfer between hdl and", "between hdl and ldl", "and ldl clark", "ldl clark et", "clark et al. 2006", "et al. 2006 .
              spherical", "al. 2006 .
              spherical hdl", "2006 .
              spherical hdl particles", ".
              spherical hdl particles can", "hdl particles can bind", "particles can bind apoc", "can bind apoc ii", "apoc ii apoc", "ii apoc iii", "apoc iii and and", "iii and and apoe", "and and apoe proteins.", "hdl high density lipoprotein", "high density lipoprotein particles", "density lipoprotein particles play", "lipoprotein particles play a", "particles play a central role", "play a central role in", "a central role in the", "central role in the reverse", "role in the reverse transport", "in the reverse transport of", "the reverse transport of cholesterol", "transport of cholesterol the", "of cholesterol the process", "cholesterol the process by", "the process by which cholesterol", "process by which cholesterol in", "by which cholesterol in tissues", "which cholesterol in tissues other", "cholesterol in tissues other than", "in tissues other than the", "tissues other than the liver", "other than the liver is", "than the liver is returned", "the liver is returned to", "liver is returned to the", "is returned to the liver", "returned to the liver for", "to the liver for conversion", "the liver for conversion to", "liver for conversion to bile", "for conversion to bile salts", "conversion to bile salts and", "to bile salts and excretion", "bile salts and excretion from", "salts and excretion from the", "and excretion from the body", "excretion from the body and", "from the body and provided", "the body and provided to", "body and provided to tissues", "and provided to tissues such", "provided to tissues such as", "to tissues such as the", "tissues such as the adrenals", "such as the adrenals and", "as the adrenals and gonads", "the adrenals and gonads for", "adrenals and gonads for steroid", "and gonads for steroid hormone", "gonads for steroid hormone synthesis", "steroid hormone synthesis tall", "hormone synthesis tall et", "synthesis tall et al.", "tall et al. 2008 .
              abcg1", "et al. 2008 .
              abcg1 mediates", "al. 2008 .
              abcg1 mediates the", "2008 .
              abcg1 mediates the movement", ".
              abcg1 mediates the movement of", "mediates the movement of intracellular", "the movement of intracellular cholesterol", "movement of intracellular cholesterol to", "of intracellular cholesterol to the", "intracellular cholesterol to the extracellular", "cholesterol to the extracellular face", "to the extracellular face of", "the extracellular face of the", "extracellular face of the plasma", "face of the plasma membrane", "of the plasma membrane where", "the plasma membrane where it", "plasma membrane where it is", "membrane where it is accessible", "where it is accessible to", "it is accessible to circulating", "is accessible to circulating hdl", "to circulating hdl vaughan", "circulating hdl vaughan &", "hdl vaughan & oram", "vaughan & oram 2005 .", "& oram 2005 . spherical", "2005 . spherical mature", "spherical mature hdl", "mature hdl particles can", "hdl particles can acquire additional", "particles can acquire additional molecules", "can acquire additional molecules of", "acquire additional molecules of free", "additional molecules of free cholesterol", "of free cholesterol chol", "cholesterol chol and", "phospholipid pl from", "pl from cell membranes.
              at", "from cell membranes.
              at the hdl", "cell membranes.
              at the hdl surface", "the hdl surface lcat", "surface lcat lecithin", "lcat lecithin cholesterol acyltransferase", "lecithin cholesterol acyltransferase associates", "cholesterol acyltransferase associates strongly", "acyltransferase associates strongly with", "associates strongly with hdl particles", "strongly with hdl particles and", "hdl particles and activated", "particles and activated by", "and activated by apoa", "by apoa i catalyzes", "apoa i catalyzes the", "i catalyzes the reaction", "catalyzes the reaction of cholesterol", "the reaction of cholesterol and", "reaction of cholesterol and phosphatidylcholine", "of cholesterol and phosphatidylcholine to", "cholesterol and phosphatidylcholine to yield", "and phosphatidylcholine to yield cholesterol", "phosphatidylcholine to yield cholesterol esterified", "to yield cholesterol esterified with", "yield cholesterol esterified with a", "cholesterol esterified with a long", "esterified with a long chain", "with a long chain fatty", "a long chain fatty acid", "long chain fatty acid and", "chain fatty acid and 2", "fatty acid and 2 lysophosphatidylcholine.", "acid and 2 lysophosphatidylcholine. the", "and 2 lysophosphatidylcholine. the hydrophobic", "2 lysophosphatidylcholine. the hydrophobic cholesterol", "lysophosphatidylcholine. the hydrophobic cholesterol ester", "the hydrophobic cholesterol ester reaction", "hydrophobic cholesterol ester reaction product", "cholesterol ester reaction product is", "ester reaction product is strongly", "reaction product is strongly associated", "product is strongly associated with", "is strongly associated with the", "strongly associated with the hdl", "associated with the hdl particle", "with the hdl particle while", "the hdl particle while the", "hdl particle while the 2", "particle while the 2 lysophosphatidylcholine", "while the 2 lysophosphatidylcholine product", "the 2 lysophosphatidylcholine product is", "2 lysophosphatidylcholine product is released.", "lysophosphatidylcholine product is released. torcetrapib", "product is released. torcetrapib associates", "is released. torcetrapib associates with", "released. torcetrapib associates with a", "torcetrapib associates with a molecule", "associates with a molecule of", "with a molecule of cetp", "a molecule of cetp and", "molecule of cetp and a", "of cetp and a spherical", "cetp and a spherical hdl", "and a spherical hdl particle", "a spherical hdl particle to", "spherical hdl particle to form", "hdl particle to form a", "particle to form a stable", "to form a stable complex", "a stable complex thus", "stable complex thus trapping", "complex thus trapping cetp", "thus trapping cetp and inhibiting", "trapping cetp and inhibiting cetp", "cetp and inhibiting cetp mediated", "and inhibiting cetp mediated lipid", "inhibiting cetp mediated lipid transfer", "cetp mediated lipid transfer between", "mediated lipid transfer between hdl", "lipid transfer between hdl and", "transfer between hdl and ldl", "hdl and ldl clark", "and ldl clark et", "ldl clark et al.", "clark et al. 2006 .
              spherical", "et al. 2006 .
              spherical hdl", "al. 2006 .
              spherical hdl particles", "2006 .
              spherical hdl particles can", ".
              spherical hdl particles can bind", "hdl particles can bind apoc", "particles can bind apoc ii", "bind apoc ii apoc", "apoc ii apoc iii", "ii apoc iii and", "apoc iii and and apoe", "iii and and apoe proteins." ] }, { "record_id": "GLY_000594_1_1180", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8964208", "r hsa", "hsa 8964208", "r hsa 8964208" ] }, { "record_id": "GLY_000594_1_1180", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phenylalanine metabolism", "the first", "first reaction", "reaction in", "in this", "this pathway", "pathway converts", "converts phenylalanine", "phenylalanine to", "to tyrosine", "coupled to", "to the", "the conversion", "conversion of", "of tetrahydrobiopterin", "tetrahydrobiopterin to", "to 4a", "4a hydroxytetrahydrobiopterin", "catalyzed by", "by phenylalanine", "phenylalanine hydroxylase.", "hydroxylase. deficiencies", "deficiencies in", "this 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synthesis", "synthesis of", "of glutamate", "glutamine from", "from ammonia", "ammonia and", "and tca", "tca cycle", "cycle intermediates", "intermediates and", "and allow", "allow the", "the utilization", "utilization of", "of the", "the carbon", "carbon atoms", "atoms from", "from these", "these amino", "amino acids", "acids for", "for glucose", "glucose synthesis", "synthesis under", "under fasting", "fasting conditions.", "conditions. these", "reactions also", "also provide", "provide a", "a means", "means to", "to collect", "collect nitrogen", "both as", "as ammonia", "and as", "as amino", "amino groups", "and direct", "direct it", "it towards", "towards urea", "urea synthesis.", "synthesis. transamination", "the conversion", "conversion of", "of an", "an amino", "amino acid", "acid to", "to the", "the corresponding", "corresponding alpha", "alpha keto", "keto acid", "acid coupled", "coupled to", "of a", "a molecule", "molecule of", "of 2", "2 oxoglutarate", "alpha ketoglutarate", 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glutamate and", "of glutamate and glutamine", "glutamate and glutamine from", "and glutamine from ammonia", "glutamine from ammonia and", "from ammonia and tca", "ammonia and tca cycle", "and tca cycle intermediates", "tca cycle intermediates and", "cycle intermediates and allow", "intermediates and allow the", "and allow the utilization", "allow the utilization of", "the utilization of the", "utilization of the carbon", "of the carbon atoms", "the carbon atoms from", "carbon atoms from these", "atoms from these amino", "from these amino acids", "these amino acids for", "amino acids for glucose", "acids for glucose synthesis", "for glucose synthesis under", "glucose synthesis under fasting", "synthesis under fasting conditions.", "under fasting conditions. these", "fasting conditions. these reactions", "conditions. these reactions also", "these reactions also provide", "reactions also provide a", "also provide a means", "provide a means to", "a means to collect", "means to collect nitrogen", "collect nitrogen both", "nitrogen both as", "both as ammonia and", "as ammonia and as", "ammonia and as amino", "and as amino groups", "amino groups and", "groups and direct", "and direct it towards", "direct it towards urea", "it towards urea synthesis.", "towards urea synthesis. transamination", "synthesis. transamination the", "transamination the conversion", "the conversion of an", "conversion of an amino", "of an amino acid", "an amino acid to", "amino acid to the", "acid to the corresponding", "to the corresponding alpha", "the corresponding alpha keto", "corresponding alpha keto acid", "alpha keto acid coupled", "keto acid coupled to", "acid coupled to the", "coupled to the conversion", "to the conversion of", "the conversion of a", "conversion of a molecule", "of a molecule of", "a molecule of 2", "molecule of 2 oxoglutarate", "2 oxoglutarate alpha", "oxoglutarate alpha ketoglutarate", "alpha ketoglutarate to", "ketoglutarate to glutamate", "to glutamate is", 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owen", "1990 owen et", "owen et al. 1979", "et al. 1979 .", "these reactions mediate the synthesis", "reactions mediate the synthesis of", "mediate the synthesis of glutamate", "the synthesis of glutamate and", "synthesis of glutamate and glutamine", "of glutamate and glutamine from", "glutamate and glutamine from ammonia", "and glutamine from ammonia and", "glutamine from ammonia and tca", "from ammonia and tca cycle", "ammonia and tca cycle intermediates", "and tca cycle intermediates and", "tca cycle intermediates and allow", "cycle intermediates and allow the", "intermediates and allow the utilization", "and allow the utilization of", "allow the utilization of the", "the utilization of the carbon", "utilization of the carbon atoms", "of the carbon atoms from", "the carbon atoms from these", "carbon atoms from these amino", "atoms from these amino acids", "from these amino acids for", "these amino acids for glucose", "amino acids for glucose synthesis", "acids for glucose synthesis 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"transamination reactions are freely reversible", "reactions are freely reversible so", "are freely reversible so they", "freely reversible so they also", "reversible so they also provide", "so they also provide a", "they also provide a means", "provide a means to balance", "a means to balance concentrations", "means to balance concentrations of", "to balance concentrations of various", "balance concentrations of various amino", "concentrations of various amino acids", "of various amino acids and", "various amino acids and 2", "amino acids and 2 oxo", "and 2 oxo alpha", "2 oxo alpha keto", "alpha keto acids in", "keto acids in the", "in the cell felig", "the cell felig 1975", "felig 1975 h\u00e4ussinger 1990", "h\u00e4ussinger 1990 owen et", "1990 owen et al.", "owen et al. 1979 ." ] }, { "record_id": "GLY_000594_1_1182", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8981607", "r hsa", "hsa 8981607", "r hsa 8981607" ] }, { 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hankeln", "in hankeln et", "hankeln et al.", "et al. 2005", "al. 2005 .", "2005 . androglobin", ". androglobin is", "androglobin is a", "is a more", "a more distantly", "more distantly related", "distantly related globin", "related globin of", "globin of uncertain", "of uncertain function", "uncertain function that", "function that is", "that is expressed", "is expressed in", "expressed in testes", "testes hoogewijs", "hoogewijs et al.", "et al. 2012", "al. 2012 .", "2012 . myoglobin", ". myoglobin is", "myoglobin is predominantly", "is predominantly expressed", "predominantly expressed in", "expressed in muscle", "in muscle tissue", "tissue reviewed", "reviewed in helbo", "in helbo et", "helbo et al.", "et al. 2013", "neuroglobin is expressed", "expressed in neurons", "neurons and", "and cytoglobin is", "cytoglobin is expressed", "expressed in connective", "in connective tissue", "connective tissue fibroblasts", "tissue fibroblasts and", "fibroblasts and smooth", "and smooth muscle", 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.", "2017 . globins", ". globins can", "globins can also", "can also regulate", "also regulate oxygen", "regulate oxygen homeostasis", "oxygen homeostasis via", "homeostasis via reactions", "via reactions with", "reactions with nitric", "with nitric oxide", "oxide no", "a vasodilator. oxygenated", "vasodilator. oxygenated globins", "oxygenated globins scavenge", "globins scavenge no", "scavenge no by", "no by oxidation", "by oxidation while", "oxidation while deoxygenated", "while deoxygenated globins", "deoxygenated globins can", "globins can act", "can act as", "act as a", "as a nitrite", "a nitrite reductase", "nitrite reductase to", "reductase to produce", "to produce no", "no reviewed", "reviewed in hendgen", "in hendgen cotta", "hendgen cotta et", "cotta et al.", "2014 tejero", "tejero and gladwin", "and gladwin 2014", "gladwin 2014 .", "globins are heme containing", "are heme containing proteins", "heme containing proteins that", "containing proteins that reversibly", "proteins 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tissue", "in connective tissue fibroblasts", "connective tissue fibroblasts and", "tissue fibroblasts and smooth", "fibroblasts and smooth muscle", "and smooth muscle cells", "muscle cells reviewed", "cells reviewed in", "reviewed in pesce et", "in pesce et al.", "pesce et al. 2002", "al. 2002 hankeln", "2002 hankeln et", "hankeln et al. 2004", "al. 2004 ascenzi", "2004 ascenzi et", "ascenzi et al. 2016", "et al. 2016 .", "al. 2016 . whereas", "2016 . whereas myoglobin", ". whereas myoglobin contains", "whereas myoglobin contains pentacoordinated", "myoglobin contains pentacoordinated heme", "contains pentacoordinated heme iron", "heme iron neuroglobin", "iron neuroglobin and", "neuroglobin and cytoglobin contain", "and cytoglobin contain hexacoordinated", "cytoglobin contain hexacoordinated heme", "contain hexacoordinated heme iron:", "hexacoordinated heme iron: the", "heme iron: the iron", "iron: the iron atom", "the iron atom is", "iron atom is bound", "atom is bound by", "is bound 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.", "al. 2010 . neuroglobin", "2010 . neuroglobin may", ". neuroglobin may function", "neuroglobin may function in", "may function in oxygen", "function in oxygen homeostasis", "oxygen homeostasis however", "homeostasis however the", "however the importance of", "the importance of its", "importance of its oxygen", "of its oxygen binding", "its oxygen binding activity", "oxygen binding activity is", "binding activity is unclear", "is unclear reviewed", "unclear reviewed in", "al. 2005 . cytoglobin", "2005 . cytoglobin may", ". cytoglobin may function", "cytoglobin may function in", "may function in nitric", "function in nitric oxide", "in nitric oxide metabolism", "oxide metabolism thuy", "metabolism thuy et", "thuy et al. 2016", "al. 2016 liu", "2016 liu et", "liu et al. 2017", "et al. 2017 .", "al. 2017 . globins", "2017 . globins can", ". globins can also", "globins can also regulate", "can also regulate oxygen", "also regulate oxygen homeostasis", "regulate oxygen homeostasis via", "oxygen homeostasis via reactions", "homeostasis via reactions with", "via reactions with nitric", "reactions with nitric oxide", "nitric oxide no", "no a", "a vasodilator. oxygenated globins", "vasodilator. oxygenated globins scavenge", "oxygenated globins scavenge no", "globins scavenge no by", "scavenge no by oxidation", "no by oxidation while", "by oxidation while deoxygenated", "oxidation while deoxygenated globins", "while deoxygenated globins can", "deoxygenated globins can act", "globins can act as", "can act as a", "act as a nitrite", "as a nitrite reductase", "a nitrite reductase to", "nitrite reductase to produce", "reductase to produce no", "produce no reviewed", "no reviewed in", "reviewed in hendgen cotta", "in hendgen cotta et", "hendgen cotta et al.", "cotta et al. 2014", "al. 2014 tejero", "2014 tejero and", "tejero and gladwin 2014", "and gladwin 2014 .", "globins are heme containing proteins", "are heme containing proteins that", "heme containing proteins that 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expressed in", "is predominantly expressed in muscle", "predominantly expressed in muscle tissue", "in muscle tissue reviewed", "muscle tissue reviewed in", "tissue reviewed in helbo", "reviewed in helbo et al.", "in helbo et al. 2013", "al. 2013 neuroglobin", "2013 neuroglobin is", "neuroglobin is expressed in neurons", "expressed in neurons and", "in neurons and cytoglobin", "neurons and cytoglobin is", "and cytoglobin is expressed in", "cytoglobin is expressed in connective", "is expressed in connective tissue", "expressed in connective tissue fibroblasts", "in connective tissue fibroblasts and", "connective tissue fibroblasts and smooth", "tissue fibroblasts and smooth muscle", "fibroblasts and smooth muscle cells", "smooth muscle cells reviewed", "muscle cells reviewed in", "cells reviewed in pesce", "reviewed in pesce et al.", "in pesce et al. 2002", "et al. 2002 hankeln", "al. 2002 hankeln et", "2002 hankeln et al.", "et al. 2004 ascenzi", "al. 2004 ascenzi et", "2004 ascenzi et al.", "ascenzi et al. 2016 .", "et al. 2016 . whereas", "al. 2016 . whereas myoglobin", "2016 . whereas myoglobin contains", ". whereas myoglobin contains pentacoordinated", "whereas myoglobin contains pentacoordinated heme", "myoglobin contains pentacoordinated heme iron", "pentacoordinated heme iron neuroglobin", "heme iron neuroglobin and", "iron neuroglobin and cytoglobin", "neuroglobin and cytoglobin contain hexacoordinated", "and cytoglobin contain hexacoordinated heme", "cytoglobin contain hexacoordinated heme iron:", "contain hexacoordinated heme iron: the", "hexacoordinated heme iron: the iron", "heme iron: the iron atom", "iron: the iron atom is", "the iron atom is bound", "iron atom is bound by", "atom is bound by 4", "is bound by 4 nitrogen", "bound by 4 nitrogen atoms", "by 4 nitrogen atoms of", "4 nitrogen atoms of heme", "nitrogen atoms of heme and", "atoms of heme and 2", "of heme and 2 histidine", "heme and 2 histidine residues", "and 2 histidine residues of", "2 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              epo", ".
              epo activates", "activates 4", "4 major", "major signaling", "signaling pathways:", "pathways: stat5", "stat5 activated", "activated transcription", "pi3k akt", "ras raf", "raf erk", "and plc", "plc pkc.", "pkc. jak2", "jak2 stat5", "stat5 activates", "activates expression", "expression of", "of bcl2l1", "bcl xl", "and therefore", "therefore appears", "appears to", "to be", "be important", "important for", "for anti", "anti apoptosis.", "apoptosis. pi3k", "akt appears", "for both", "both anti", "anti apoptosis", "apoptosis and", "and proliferation.", "proliferation. the", "the roles", "roles of", "of other", "other signaling", "signaling pathways", "pathways are", "are controversial", "controversial but", "but both", "both ras", "raf mek", "mek erk", "erk and", "and plcgamma", "plcgamma pkc", "pkc have", "have mitogenic", "mitogenic effects.", "effects. phosphatases", "phosphatases such", "as shp1", "shp1 are", "are also", "also recruited", "recruited and", "and downregulate", "downregulate the", "the epo", "epo signal.
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              the", "cells.
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              epo activates", ".
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              epo", "epo signal.
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              epo also has", "also has effects", "has effects outside", "effects outside of", "outside of erythropoiesis.", "of erythropoiesis. the", "erythropoiesis. the epor", "the epor is", "epor is expressed", "is expressed in", "expressed in various", "in various tissues", "various tissues such", "tissues such as", "such as endothelium", "as endothelium where", "endothelium where it", "where it can", "it can act", "can act to", "act to stimulate", "to stimulate growth", "stimulate growth and", "growth and promote", "and promote cell", "promote cell survival", "survival debeljak", "debeljak et al.", "2014 kim\u00e1kov\u00e1", "kim\u00e1kov\u00e1 et al.", "et al. 2017", "al. 2017 .", "2017 . epo", ". epo and", "epo and epor", "and epor in", "epor in the", "in the neurovascular", "the neurovascular system", "neurovascular system act", "system act via", "act via akt", "akt wnt1", "wnt1 mtor", "mtor sirt1", "sirt1 and", "and foxo proteins", "foxo proteins to", "proteins to prevent", "to prevent apoptotic", "prevent apoptotic cell", "apoptotic cell injury", "injury reviewed", "in ostrowski", "ostrowski and heinrich", "and heinrich 2018", "2018 maiese", "2016 and", "and epo may", "epo may have", "may have therapeutic", "have therapeutic value", "therapeutic value in", "value in the", "in the nervous", "the nervous system", "system ma", "ma et al.", "al. 2016 .", "epo is a", "is a cytokine that", "a cytokine that serves", "cytokine that serves as", "that serves as the", "serves as the primary", "as the primary regulator", "the primary regulator of", "primary regulator of erythropoiesis", "of erythropoiesis the", "erythropoiesis the differentiation", "the differentiation of erythrocytes", "differentiation of erythrocytes from", "of erythrocytes from stem", "erythrocytes from stem cells", "from stem cells in", "stem cells in the", "cells in the liver", "in the liver of", "the liver of the", "liver of the fetus", "of the fetus and", "the fetus and the", "fetus and the bone", "and the bone marrow", "the bone marrow of", "bone marrow of adult", "marrow of adult mammals", "adult mammals reviewed", "mammals reviewed in", "reviewed in ingley 2012", "ingley 2012 zhang", "2012 zhang et", "zhang et al. 2014", "al. 2014 kuhrt", "2014 kuhrt and", "kuhrt and wojchowski 2015", "and wojchowski 2015 .", "wojchowski 2015 . epo", "2015 . epo is", ". epo is produced", "epo is produced in", "is produced in the", "produced in the kidneys", "in the kidneys in", "the kidneys in response", "kidneys in response to", "in response to low", "response to low oxygen", "to low oxygen tension", "low oxygen tension and", "oxygen tension and binds", "tension and binds a", "and binds a receptor", "a receptor epor", "epor located on", "located on progenitor cells:", "on progenitor cells: burst", "progenitor cells: burst forming", "cells: burst forming unit", "burst forming unit erythroid", "unit erythroid bfu", "erythroid bfu e", "bfu e cells", "e cells and", "cells and colony forming", "and colony forming unit", "colony forming unit erythroid", "unit erythroid cfu", "erythroid cfu e", "cfu e cells.
              the", "e cells.
              the erythropoietin", "erythropoietin receptor epor", "epor exists in", "exists in lipid rafts", "lipid rafts reviewed", "rafts reviewed in", "reviewed in mcgraw and", "in mcgraw and list", "mcgraw and list 2017", "list 2017 as", "2017 as a", "as a dimer pre", "a dimer pre associated", "dimer pre associated with", "pre associated with proteins", "associated with proteins involved", "with proteins involved in", "proteins involved in downstream", "involved in downstream signaling:", "in downstream signaling: the", "downstream signaling: the tyrosine", "signaling: the tyrosine kinase", "the tyrosine kinase jak2", "kinase jak2 the", "jak2 the tyrosine", "the tyrosine kinase lyn", "kinase lyn and", "lyn and the", "and the scaffold protein", "the scaffold protein irs2.", "scaffold protein irs2. binding", "protein irs2. binding of", "irs2. binding of epo", "binding of epo to", "of epo to the", "epo to the epor", "to the epor dimer", "the epor dimer causes", "epor dimer causes a", "dimer causes a change", "causes a change in", "a change in conformation", "in conformation reviewed", "conformation reviewed in", "reviewed in watowich et", "in watowich et al.", "watowich et al. 2011", "al. 2011 corbett", "2011 corbett et", "corbett et al. 2016", "al. 2016 that", "2016 that activates", "activates jak2 which", "jak2 which then", "which then transphosphorylates jak2", "then transphosphorylates jak2 and", "transphosphorylates jak2 and phosphorylates", "jak2 and phosphorylates the", "and phosphorylates the cytoplasmic", "phosphorylates the cytoplasmic domain", "the cytoplasmic domain of", "cytoplasmic domain of epor.", "domain of epor. the", "of epor. the phosphorylated", "epor. the phosphorylated epor", "the phosphorylated epor serves", "phosphorylated epor serves directly", "epor serves directly or", "serves directly or indirectly", "directly or indirectly as", "or indirectly as a", "indirectly as a docking", "as a docking site", "a docking site for", "docking site for signaling", "site for signaling molecules", "for signaling molecules such", "signaling molecules such as", "molecules such as stat5", "as stat5 phosphatidylinositol", "stat5 phosphatidylinositol 4", "phosphatidylinositol 4 5 bisphosphate", "4 5 bisphosphate 3", "5 bisphosphate 3 kinase", "3 kinase pi3k", "pi3k phospholipase", "c gamma plcg1", "plcg2 and", "and activators of ras", "of ras shc1", "grb2:sos1 grb2:vav1 .
              epo", "grb2:vav1 .
              epo activates 4", ".
              epo activates 4 major", "activates 4 major signaling", "4 major signaling pathways:", "major signaling pathways: stat5", "signaling pathways: stat5 activated", "pathways: stat5 activated transcription", "activated transcription pi3k", "transcription pi3k akt", "pi3k akt ras", "akt ras raf", "raf erk and", "erk and plc", "and plc pkc. jak2", "plc pkc. jak2 stat5", "pkc. jak2 stat5 activates", "jak2 stat5 activates expression", "stat5 activates expression of", "activates expression of bcl2l1", "of bcl2l1 bcl", "bcl2l1 bcl xl", "bcl xl and", "xl and therefore", "and therefore appears to", "therefore appears to be", "appears to be important", "to be important for", "be important for anti", "important for anti apoptosis.", "for anti apoptosis. pi3k", "anti apoptosis. pi3k akt", "apoptosis. pi3k akt appears", "pi3k akt appears to", "akt appears to be", "be important for both", "important for both anti", "for both anti apoptosis", "both anti apoptosis and", "anti apoptosis and proliferation.", "apoptosis and proliferation. the", "and proliferation. the roles", "proliferation. the roles of", "the roles of other", "roles of other signaling", "of other signaling pathways", "other signaling pathways are", "signaling pathways are controversial", "pathways are controversial but", "are controversial but both", "controversial but both ras", "but both ras raf", "both ras raf mek", "ras raf mek erk", "raf mek erk and", "mek erk and plcgamma", "erk and plcgamma pkc", "and plcgamma pkc have", "plcgamma pkc have mitogenic", "pkc have mitogenic effects.", "have mitogenic effects. phosphatases", "mitogenic effects. phosphatases such", "effects. phosphatases such as", "phosphatases such as shp1", "such as shp1 are", "as shp1 are also", "shp1 are also recruited", "are also recruited and", "also recruited and downregulate", "recruited and downregulate the", "and downregulate the epo", "downregulate the epo signal.
              epo", "the epo signal.
              epo also", "epo signal.
              epo also has", "signal.
              epo also has effects", "also has effects outside", "has effects outside of", "effects outside of erythropoiesis.", "outside of erythropoiesis. the", "of erythropoiesis. the epor", "erythropoiesis. the epor is", "the epor is expressed", "epor is expressed in", "is expressed in various", "expressed in various tissues", "in various tissues such", "various tissues such as", "tissues such as endothelium", "such as endothelium where", "as endothelium where it", "endothelium where it can", "where it can act", "it can act to", "can act to stimulate", "act to stimulate growth", "to stimulate growth and", "stimulate growth and promote", "growth and promote cell", "and promote cell survival", "cell survival debeljak", "survival debeljak et", "debeljak et al. 2014", "al. 2014 kim\u00e1kov\u00e1", "2014 kim\u00e1kov\u00e1 et", "kim\u00e1kov\u00e1 et al. 2017", "et al. 2017 .", "al. 2017 . epo", "2017 . epo and", ". epo and epor", "epo and epor in", "and epor in the", "epor in the neurovascular", "in the neurovascular system", "the neurovascular system act", "neurovascular system act via", "system act via akt", "via akt wnt1", "sirt1 and foxo", "and foxo proteins to", "foxo proteins to prevent", "proteins to prevent apoptotic", "to prevent apoptotic cell", "prevent apoptotic cell injury", "cell injury reviewed", "injury reviewed in", "reviewed in ostrowski", "in ostrowski and", "ostrowski and heinrich 2018", "heinrich 2018 maiese", "2018 maiese 2016", "maiese 2016 and", "2016 and epo", "and epo may have", "epo may have therapeutic", "may have therapeutic value", "have therapeutic value in", "therapeutic value in the", "value in the nervous", "in the nervous system", "nervous system ma", "system ma et", "ma et al. 2016", "et al. 2016 .", "erythropoietin epo is", "epo is a cytokine", "is a cytokine that serves", "a cytokine that serves as", "cytokine that serves as the", "that serves as the primary", "serves as the primary regulator", "as the primary regulator of", "the primary regulator of erythropoiesis", "regulator of erythropoiesis the", "of erythropoiesis the differentiation", "erythropoiesis the differentiation of", "the differentiation of erythrocytes from", "differentiation of erythrocytes from stem", "of erythrocytes from stem cells", "erythrocytes from stem cells in", "from stem cells in the", "stem cells in the liver", "cells in the liver of", "in the liver of the", "the liver of the fetus", "liver of the fetus and", "of the fetus and the", "the fetus and the bone", "fetus and the bone marrow", "and the bone marrow of", "the bone marrow of adult", "bone marrow of adult mammals", "of adult mammals reviewed", "adult mammals reviewed in", "mammals reviewed in ingley", "in ingley 2012 zhang", "ingley 2012 zhang et", "2012 zhang et al.", "et al. 2014 kuhrt", "al. 2014 kuhrt and", "2014 kuhrt and wojchowski", "kuhrt and wojchowski 2015 .", "and wojchowski 2015 . epo", "wojchowski 2015 . epo is", "2015 . epo is produced", ". epo is produced in", "epo is produced in the", "is produced in the kidneys", "produced in the kidneys in", "in the kidneys in response", "the kidneys in response to", "kidneys in response to low", "in response to low oxygen", "response to low oxygen tension", "to low oxygen tension and", "low oxygen tension and binds", "oxygen tension and binds a", "tension and binds a receptor", "binds a receptor epor", "receptor epor located", "epor located on progenitor", "located on progenitor cells: burst", "on progenitor cells: burst forming", "progenitor cells: burst forming unit", "cells: burst forming unit erythroid", "forming unit erythroid bfu", "unit erythroid bfu e", "bfu e cells and", "e cells and colony", "cells and colony forming unit", "and colony forming unit erythroid", "forming unit erythroid cfu", "unit erythroid cfu e", "cfu e cells.
              the erythropoietin", "e cells.
              the erythropoietin receptor", "cells.
              the erythropoietin receptor epor", "receptor epor exists", "epor exists in lipid", "in lipid rafts reviewed", "lipid rafts reviewed in", "rafts reviewed in mcgraw", "reviewed in mcgraw and list", "in mcgraw and list 2017", "and list 2017 as", "list 2017 as a", "2017 as a dimer", "as a dimer pre associated", "a dimer pre associated with", "dimer pre associated with proteins", "pre associated with proteins involved", "associated with proteins involved in", "with proteins involved in downstream", "proteins involved in downstream signaling:", "involved in downstream signaling: the", "in downstream signaling: the tyrosine", "downstream signaling: the tyrosine kinase", "signaling: the tyrosine kinase jak2", "tyrosine kinase jak2 the", "kinase jak2 the tyrosine", "jak2 the tyrosine kinase", "tyrosine kinase lyn and", "kinase lyn and the", "lyn and the scaffold", "and the scaffold protein irs2.", "the scaffold protein irs2. binding", "scaffold protein irs2. binding of", "protein irs2. binding of epo", "irs2. binding of epo to", "binding of epo to the", "of epo to the epor", "epo to the epor dimer", "to the epor dimer causes", "the epor dimer causes a", "epor dimer causes a change", "dimer causes a change in", "causes a change in conformation", "change in conformation reviewed", "in conformation reviewed in", "conformation reviewed in watowich", "reviewed in watowich et al.", "in watowich et al. 2011", "et al. 2011 corbett", "al. 2011 corbett et", "2011 corbett et al.", "et al. 2016 that", "al. 2016 that activates", "2016 that activates jak2", "that activates jak2 which", "activates jak2 which then", "jak2 which then transphosphorylates", "which then transphosphorylates jak2 and", "then transphosphorylates jak2 and phosphorylates", "transphosphorylates jak2 and phosphorylates the", "jak2 and phosphorylates the cytoplasmic", "and phosphorylates the cytoplasmic domain", "phosphorylates the cytoplasmic domain of", "the cytoplasmic domain of epor.", "cytoplasmic domain of epor. the", "domain of epor. the phosphorylated", "of epor. the phosphorylated epor", "epor. the phosphorylated epor serves", "the phosphorylated epor serves directly", "phosphorylated epor serves directly or", "epor serves directly or indirectly", "serves directly or indirectly as", "directly or indirectly as a", "or indirectly as a docking", "indirectly as a docking site", "as a docking site for", "a docking site for signaling", "docking site for signaling molecules", "site for signaling molecules such", "for signaling molecules such as", "signaling molecules such as stat5", "such as stat5 phosphatidylinositol", "as stat5 phosphatidylinositol 4", "stat5 phosphatidylinositol 4 5", "phosphatidylinositol 4 5 bisphosphate 3", "4 5 bisphosphate 3 kinase", "bisphosphate 3 kinase pi3k", "pi3k phospholipase c", "phospholipase c gamma plcg1", "gamma plcg1 plcg2", "plcg2 and activators", "activators of ras shc1", "ras shc1 grb2:sos1", "shc1 grb2:sos1 grb2:vav1", "grb2:sos1 grb2:vav1 .
              epo activates", "grb2:vav1 .
              epo activates 4 major", ".
              epo activates 4 major signaling", "activates 4 major signaling pathways:", "4 major signaling pathways: stat5", "major signaling pathways: stat5 activated", "signaling pathways: stat5 activated transcription", "stat5 activated transcription pi3k", "activated transcription pi3k akt", "pi3k akt ras raf", "akt ras raf erk", "ras raf erk and", "raf erk and plc", "erk and plc pkc.", "and plc pkc. jak2 stat5", "plc pkc. jak2 stat5 activates", "pkc. jak2 stat5 activates expression", "jak2 stat5 activates expression of", "stat5 activates expression of bcl2l1", "expression of bcl2l1 bcl", "of bcl2l1 bcl xl", "bcl xl and therefore", "xl and therefore appears", "and therefore appears to be", "therefore appears to be important", "appears to be important for", "to be important for anti", "be important for anti apoptosis.", "important for anti apoptosis. pi3k", "for anti apoptosis. pi3k akt", "anti apoptosis. pi3k akt appears", "apoptosis. pi3k akt appears to", "pi3k akt appears to be", "akt appears to be important", "to be important for both", "be important for both anti", "important for both anti apoptosis", "for both anti apoptosis and", "both anti apoptosis and proliferation.", "anti apoptosis and proliferation. the", "apoptosis and proliferation. the roles", "and proliferation. the roles of", "proliferation. the roles of other", "the roles of other signaling", "roles of other signaling pathways", "of other signaling pathways are", "other signaling pathways are controversial", "signaling pathways are controversial but", "pathways are controversial but both", "are controversial but both ras", "controversial but both ras raf", "but both ras raf mek", "both ras raf mek erk", "ras raf mek erk and", "raf mek erk and plcgamma", "mek erk and plcgamma pkc", "erk and plcgamma pkc have", "and plcgamma pkc have mitogenic", "plcgamma pkc have mitogenic effects.", "pkc have mitogenic effects. phosphatases", "have mitogenic effects. phosphatases such", "mitogenic effects. phosphatases such as", "effects. phosphatases such as shp1", "phosphatases such as shp1 are", "such as shp1 are also", "as shp1 are also recruited", "shp1 are also recruited and", "are also recruited and downregulate", "also recruited and downregulate the", "recruited and downregulate the epo", "and downregulate the epo signal.
              epo", "downregulate the epo signal.
              epo also", "the epo signal.
              epo also has", "epo signal.
              epo also has effects", "signal.
              epo also has effects outside", "also has effects outside of", "has effects outside of erythropoiesis.", "effects outside of erythropoiesis. the", "outside of erythropoiesis. the epor", "of erythropoiesis. the epor is", "erythropoiesis. the epor is expressed", "the epor is expressed in", "epor is expressed in various", "is expressed in various tissues", "expressed in various tissues such", "in various tissues such as", "various tissues such as endothelium", "tissues such as endothelium where", "such as endothelium where it", "as endothelium where it can", "endothelium where it can act", "where it can act to", "it can act to stimulate", "can act to stimulate growth", "act to stimulate growth and", "to stimulate growth and promote", "stimulate growth and promote cell", "growth and promote cell survival", "promote cell survival debeljak", "cell survival debeljak et", "survival debeljak et al.", "et al. 2014 kim\u00e1kov\u00e1", "al. 2014 kim\u00e1kov\u00e1 et", "2014 kim\u00e1kov\u00e1 et al.", "kim\u00e1kov\u00e1 et al. 2017 .", "et al. 2017 . epo", "al. 2017 . epo and", "2017 . epo and epor", ". epo and epor in", "epo and epor in the", "and epor in the neurovascular", "epor in the neurovascular system", "in the neurovascular system act", "the neurovascular system act via", "neurovascular system act via akt", "act via akt wnt1", "akt wnt1 mtor", "wnt1 mtor sirt1", "mtor sirt1 and", "sirt1 and foxo proteins", "and foxo proteins to prevent", "foxo proteins to prevent apoptotic", "proteins to prevent apoptotic cell", "to prevent apoptotic cell injury", "apoptotic cell injury reviewed", "cell injury reviewed in", "reviewed in ostrowski and", "in ostrowski and heinrich", "and heinrich 2018 maiese", "heinrich 2018 maiese 2016", "maiese 2016 and epo", "2016 and epo may", "and epo may have therapeutic", "epo may have therapeutic value", "may have therapeutic value in", "have therapeutic value in the", "therapeutic value in the nervous", "value in the nervous system", "the nervous system ma", "nervous system ma et", "system ma et al.", "ma et al. 2016 ." ] }, { "record_id": "GLY_000594_1_1187", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9008059", "r hsa", "hsa 9008059", "r hsa 9008059" ] }, { "record_id": "GLY_000594_1_1187", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 37", "37 signaling", "interleukin 37 signaling", "are immunomodulatory", "immunomodulatory proteins", "proteins that", "that elicit", "elicit a", "a wide", "wide array", "array of", "of responses", "responses in", "in cells", "cells and", "and tissues.", "tissues. interleukin", "also known", "known as", "as il", "il 1f7", "is a", "a member", "member of", "of the", "the il", "il 1", "1 family", "sharma et", "et al.", "al. 2008", "2008 .", ". isoform", "isoform b", "b of", "of il37", "referred just", "just as", "as il37", "is synthesized", "synthesized as", "as a", "a precursor", "precursor that", "that requires", "requires processing", "primarily by", "by caspase", "caspase 1", "to attain", "attain full", "full receptor", "receptor agonist", "agonist or", "or antagonist", "antagonist function", "kumar et", "al. 2002", "2002 .", ". both", "both full", "full length", "length and", "and processed", "processed il37", "il37 can", "can bind", "bind to", "to the", "il 18", "18 binding", "binding protein", "il 18bp", "and the", "the interleukin", "interleukin 18", "18 receptor", "receptor 1", "il 18r1", "shi et", "al. 2003", "2003 .", ". upon", "upon binding", "binding to", "the il18r1", "il37 recruits", "recruits single", "single ig", "ig il", "1 related", "related receptor", "nold petry", "petry et", "al. 2015", "2015 .", ". the", "the il37:il18r1", "il37:il18r1 complex", "complex can", "can activate", "activate phosphorylation", "phosphorylation of", "of signal", "signal transducer", "transducer and", "and activator", "activator of", "of transcription", "transcription 3", "tyrosine protein", "protein kinase", "kinase mer", "mer and", "and phosphatidylinositol", "phosphatidylinositol 3", "3 4", "4 5", "5 trisphosphate", "trisphosphate 3", "3 phosphatase", "phosphatase and", "and dual", "dual specificity", "specificity protein", "protein phosphatase", "phosphatase pten", "pten and", "and can", "can also", "also inhibit", "inhibit nuclear", "nuclear factor", "factor nf", "nf kappa", "kappa b", "b p105", "p105 subunit", ". processed", "can be", "be secreted", "secreted from", "from the", "the cytosol", "cytosol to", "the extracellular", "extracellular space", "space or", "or translocated", "translocated into", "into the", "the nucleus", "bulau et", "al. 2014", "2014 .", ". full", "length il37", "also be", "bind with", "with mothers", "mothers against", "against decapentaplegic", "decapentaplegic homolog", "homolog 3", "in the", "cytosol and", "and then", "then translocate", "translocate to", "where it", "it facilitates", "facilitates transcription", "transcription of", "of tyrosine", "phosphatase non", "non receptors", "nold et", "al. 2010", "luo et", "al. 2017", "2017 .", ". these", "these events", "events ultimately", "ultimately lead", "lead to", "to suppression", "suppression of", "of cytokine", "cytokine production", "production in", "in several", "several types", "types of", "of immune", "immune cells", "cells resulting", "resulting in", "in reduced", "reduced inflammation.", "interleukins il", "il are", "are immunomodulatory proteins", "immunomodulatory proteins that", "proteins that elicit", "that elicit a", "elicit a wide", "a wide array", "wide array of", "array of responses", "of responses in", "responses in cells", "in cells and", "cells and tissues.", "and tissues. interleukin", "tissues. interleukin 37", "37 il37", "also known as", "known as il", "as il 1f7", "1f7 is", "is a member", "a member of", "member of the", "of the il", "the il 1", "il 1 family", "family sharma", "sharma et al.", "et al. 2008", "al. 2008 .", "2008 . isoform", ". isoform b", "isoform b of", "b of il37", "il37 referred", "referred just as", "just as il37", "il37 is", "is synthesized as", "synthesized as a", "as a precursor", "a precursor that", "precursor that requires", "that requires processing", "processing primarily", "primarily by caspase", "by caspase 1", "1 to", "to attain full", "attain full receptor", "full receptor agonist", "receptor agonist or", "agonist or antagonist", "or antagonist function", "function kumar", "kumar et al.", "et al. 2002", "al. 2002 .", "2002 . both", ". both full", "both full length", "full length and", "length and processed", "and processed il37", "processed il37 can", "il37 can bind", "can bind to", "bind to the", "to the il", "the il 18", "il 18 binding", "18 binding protein", "protein il", "18bp and", "and the interleukin", "the interleukin 18", "interleukin 18 receptor", "18 receptor 1", "1 il", "shi et al.", "et al. 2003", "al. 2003 .", "2003 . upon", ". 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phosphatase", "protein phosphatase pten", "phosphatase pten and", "pten and can", "and can also", "can also inhibit", "also inhibit nuclear", "inhibit nuclear factor", "nuclear factor nf", "factor nf kappa", "nf kappa b", "kappa b p105", "b p105 subunit", "subunit nfkb", "2015 . processed", ". processed il37", "il37 can be", "can be secreted", "be secreted from", "secreted from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the extracellular", "the extracellular space", "extracellular space or", "space or translocated", "or translocated into", "translocated into the", "into the nucleus", "nucleus bulau", "bulau et al.", "et al. 2014", "al. 2014 .", "2014 . full", ". full length", "full length il37", "length il37 can", "il37 can also", "can also be", "also be secreted", "space bulau", "2014 . processed", "can bind with", "bind with mothers", "with mothers against", "mothers against decapentaplegic", "against decapentaplegic homolog", "decapentaplegic homolog 3", "3 smad3", "smad3 in", "in the cytosol", "the cytosol and", "cytosol and then", "and then translocate", "then translocate to", "translocate to the", "to the nucleus", "nucleus where", "where it facilitates", "it facilitates transcription", "facilitates transcription of", "transcription of tyrosine", "of tyrosine protein", "tyrosine protein phosphatase", "protein phosphatase non", "phosphatase non receptors", "receptors ptpns", "nold et al.", "et al. 2010", "2010 luo", "luo et al.", "et al. 2017", "al. 2017 .", "2017 . these", ". these events", "these events ultimately", "events ultimately lead", "ultimately lead to", "lead to suppression", "to suppression of", "suppression of cytokine", "of cytokine production", "cytokine production in", "production in several", "in several types", "several types of", "types of immune", "of immune cells", "immune cells resulting", "cells resulting in", "resulting in reduced", "in reduced inflammation.", "il are immunomodulatory", "are immunomodulatory proteins that", "immunomodulatory proteins that elicit", "proteins that elicit a", "that elicit a wide", "elicit a wide array", "a wide array of", "wide array of responses", "array of responses in", "of responses in cells", "responses in cells and", "in cells and tissues.", "cells and tissues. interleukin", "and tissues. interleukin 37", "interleukin 37 il37", "il37 also", "also known as il", "known as il 1f7", "il 1f7 is", "1f7 is a", "is a member of", "a member of the", "member of the il", "of the il 1", "the il 1 family", "1 family sharma", "family sharma et", "sharma et al. 2008", "et al. 2008 .", "al. 2008 . isoform", "2008 . isoform b", ". isoform b of", "isoform b of il37", "of il37 referred", "il37 referred just", "referred just as il37", "as il37 is", "il37 is synthesized", "is synthesized as a", "synthesized as a precursor", "as a precursor that", "a precursor that requires", "precursor that requires processing", "requires processing primarily", "processing primarily by", "primarily by caspase 1", "caspase 1 to", "1 to attain", "to attain full receptor", "attain full receptor agonist", "full receptor agonist or", "receptor agonist or antagonist", "agonist or antagonist function", "antagonist function kumar", "function kumar et", "kumar et al. 2002", "et al. 2002 .", "al. 2002 . both", "2002 . both full", ". both full length", "both full length and", "full length and processed", "length and processed il37", "and processed il37 can", "processed il37 can bind", "il37 can bind to", "can bind to the", "bind to the il", "to the il 18", "the il 18 binding", "il 18 binding protein", "binding protein il", "protein il 18bp", "il 18bp and", "18bp and the", "and the interleukin 18", "the interleukin 18 receptor", "interleukin 18 receptor 1", "receptor 1 il", "1 il 18r1", "18r1 shi", "shi et al. 2003", "et al. 2003 .", "al. 2003 . upon", "2003 . upon binding", ". upon binding to", "upon binding to the", "binding to the il18r1", "the il18r1 il37", "il18r1 il37 recruits", "il37 recruits single ig", "recruits single ig il", "single ig il 1", "ig il 1 related", "il 1 related receptor", "related receptor sigirr", "sigirr nold", "nold petry et al.", "petry et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the il37:il18r1", ". the il37:il18r1 complex", "the il37:il18r1 complex can", "il37:il18r1 complex can activate", "complex can activate phosphorylation", "can activate phosphorylation of", "activate phosphorylation of signal", "phosphorylation of signal transducer", "of signal transducer and", "signal transducer and activator", "transducer and activator of", "and activator of transcription", "activator of transcription 3", "transcription 3 stat3", "stat3 tyrosine", "tyrosine protein kinase mer", "protein kinase mer and", "kinase mer and phosphatidylinositol", "mer and phosphatidylinositol 3", "and phosphatidylinositol 3 4", "phosphatidylinositol 3 4 5", "3 4 5 trisphosphate", "4 5 trisphosphate 3", "5 trisphosphate 3 phosphatase", "trisphosphate 3 phosphatase and", "3 phosphatase and dual", "phosphatase and dual specificity", "and dual specificity protein", "dual specificity protein phosphatase", "specificity protein phosphatase pten", "protein phosphatase pten and", "phosphatase pten and can", "pten and can also", "and can also inhibit", "can also inhibit nuclear", "also inhibit nuclear factor", "inhibit nuclear factor nf", "nuclear factor nf kappa", "factor nf kappa b", "nf kappa b p105", "kappa b p105 subunit", "p105 subunit nfkb", "nfkb nold", "al. 2015 . processed", "2015 . processed il37", ". processed il37 can", "processed il37 can be", "il37 can be secreted", "can be secreted from", "be secreted from the", "secreted from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the extracellular", "to the extracellular space", "the extracellular space or", "extracellular space or translocated", "space or translocated into", "or translocated into the", "translocated into the nucleus", "the nucleus bulau", "nucleus bulau et", "bulau et al. 2014", "et al. 2014 .", "al. 2014 . full", "2014 . full length", ". full length il37", "full length il37 can", "length il37 can also", "il37 can also be", "can also be secreted", "also be secreted from", "extracellular space bulau", "space bulau et", "al. 2014 . processed", "2014 . processed il37", "il37 can bind with", "can bind with mothers", "bind with mothers against", "with mothers against decapentaplegic", "mothers against decapentaplegic homolog", "against decapentaplegic homolog 3", "homolog 3 smad3", "smad3 in the", "in the cytosol and", "the cytosol and then", "cytosol and then translocate", "and then translocate to", "then translocate to the", "translocate to the nucleus", "the nucleus where", "nucleus where it", "where it facilitates transcription", "it facilitates transcription of", "facilitates transcription of tyrosine", "transcription of tyrosine protein", "of tyrosine protein phosphatase", "tyrosine protein phosphatase non", "protein phosphatase non receptors", "non receptors ptpns", "ptpns nold", "nold et al. 2010", "al. 2010 luo", "2010 luo et", "luo et al. 2017", "et al. 2017 .", "al. 2017 . these", "2017 . these events", ". these events ultimately", "these events ultimately lead", "events ultimately lead to", "ultimately lead to suppression", "lead to suppression of", "to suppression of cytokine", "suppression of cytokine production", "of cytokine production in", "cytokine production in several", "production in several types", "in several types of", "several types of immune", "types of immune cells", "of immune cells resulting", "immune cells resulting in", "cells resulting in reduced", "resulting in reduced inflammation.", "interleukins il are", "il are immunomodulatory proteins", "are immunomodulatory proteins that elicit", "immunomodulatory proteins that elicit a", "proteins that elicit a wide", "that elicit a wide array", "elicit a wide array of", "a wide array of responses", "wide array of responses in", "array of responses in cells", "of responses in cells and", "responses in cells and tissues.", "in cells and tissues. interleukin", "cells and tissues. interleukin 37", "tissues. interleukin 37 il37", "il37 also known", "also known as il 1f7", "as il 1f7 is", "il 1f7 is a", "1f7 is a member", "is a member of the", "a member of the il", "member of the il 1", "of the il 1 family", "il 1 family sharma", "1 family sharma et", "family sharma et al.", "sharma et al. 2008 .", "et al. 2008 . isoform", "al. 2008 . isoform b", "2008 . isoform b of", ". isoform b of il37", "b of il37 referred", "of il37 referred just", "il37 referred just as", "just as il37 is", "as il37 is synthesized", "il37 is synthesized as", "is synthesized as a precursor", "synthesized as a precursor that", "as a precursor that requires", "a precursor that requires processing", "that requires processing primarily", "requires processing primarily by", "processing primarily by caspase", "by caspase 1 to", "caspase 1 to attain", "1 to attain full", "to attain full receptor agonist", "attain full receptor agonist or", "full receptor agonist or antagonist", "receptor agonist or antagonist function", "or antagonist function kumar", "antagonist function kumar et", "function kumar et al.", "kumar et al. 2002 .", "et al. 2002 . both", "al. 2002 . both full", "2002 . both full length", ". both full length and", "both full length and processed", "full length and processed il37", "length and processed il37 can", "and processed il37 can bind", "processed il37 can bind to", "il37 can bind to the", "can bind to the il", "bind to the il 18", "to the il 18 binding", "the il 18 binding protein", "18 binding protein il", "binding protein il 18bp", "il 18bp and the", "18bp and the interleukin", "and the interleukin 18 receptor", "the interleukin 18 receptor 1", "18 receptor 1 il", "receptor 1 il 18r1", "il 18r1 shi", "18r1 shi et", "shi et al. 2003 .", "et al. 2003 . upon", "al. 2003 . upon binding", "2003 . upon binding to", ". upon binding to the", "upon binding to the il18r1", "to the il18r1 il37", "the il18r1 il37 recruits", "il18r1 il37 recruits single", "il37 recruits single ig il", "recruits single ig il 1", "single ig il 1 related", "ig il 1 related receptor", "1 related receptor sigirr", "sigirr nold petry", "nold petry et al. 2015", "petry et al. 2015 .", "et al. 2015 . the", "al. 2015 . the il37:il18r1", "2015 . the il37:il18r1 complex", ". the il37:il18r1 complex can", "the il37:il18r1 complex can activate", "il37:il18r1 complex can activate phosphorylation", "complex can activate phosphorylation of", "can activate phosphorylation of signal", "activate phosphorylation of signal transducer", "phosphorylation of signal transducer and", "of signal transducer and activator", "signal transducer and activator of", "transducer and activator of transcription", "and activator of transcription 3", "of transcription 3 stat3", "stat3 tyrosine protein", "tyrosine protein kinase mer and", "protein kinase mer and phosphatidylinositol", "kinase mer and phosphatidylinositol 3", "mer and phosphatidylinositol 3 4", "and phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "3 4 5 trisphosphate 3", "4 5 trisphosphate 3 phosphatase", "5 trisphosphate 3 phosphatase and", "trisphosphate 3 phosphatase and dual", "3 phosphatase and dual specificity", "phosphatase and dual specificity protein", "and dual specificity protein phosphatase", "dual specificity protein phosphatase pten", "specificity protein phosphatase pten and", "protein phosphatase pten and can", "phosphatase pten and can also", "pten and can also inhibit", "and can also inhibit nuclear", "can also inhibit nuclear factor", "also inhibit nuclear factor nf", "inhibit nuclear factor nf kappa", "nuclear factor nf kappa b", "factor nf kappa b p105", "nf kappa b p105 subunit", "b p105 subunit nfkb", "nfkb nold petry", "et al. 2015 . processed", "al. 2015 . processed il37", "2015 . processed il37 can", ". processed il37 can be", "processed il37 can be secreted", "il37 can be secreted from", "can be secreted from the", "be secreted from the cytosol", "secreted from the cytosol to", "from the cytosol to the", "the cytosol to the extracellular", "cytosol to the extracellular space", "to the extracellular space or", "the extracellular space or translocated", "extracellular space or translocated into", "space or translocated into the", "or translocated into the nucleus", "into the nucleus bulau", "the nucleus bulau et", "nucleus bulau et al.", "bulau et al. 2014 .", "et al. 2014 . full", "al. 2014 . full length", "2014 . full length il37", ". full length il37 can", "full length il37 can also", "length il37 can also be", "il37 can also be secreted", "can also be secreted from", "also be secreted from the", "the extracellular space bulau", "extracellular space bulau et", "space bulau et al.", "et al. 2014 . processed", "al. 2014 . processed il37", "2014 . processed il37 can", ". processed il37 can bind", "processed il37 can bind with", "il37 can bind with mothers", "can bind with mothers against", "bind with mothers against decapentaplegic", "with mothers against decapentaplegic homolog", "mothers against decapentaplegic homolog 3", "decapentaplegic homolog 3 smad3", "3 smad3 in", "smad3 in the cytosol", "in the cytosol and then", "the cytosol and then translocate", "cytosol and then translocate to", "and then translocate to the", "then translocate to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it facilitates", "where it facilitates transcription of", "it facilitates transcription of tyrosine", "facilitates transcription of tyrosine protein", "transcription of tyrosine protein phosphatase", "of tyrosine protein phosphatase non", "tyrosine protein phosphatase non receptors", "phosphatase non receptors ptpns", "ptpns nold et", "et al. 2010 luo", "al. 2010 luo et", "2010 luo et al.", "luo et al. 2017 .", "et al. 2017 . these", "al. 2017 . these events", "2017 . these events ultimately", ". these events ultimately lead", "these events ultimately lead to", "events ultimately lead to suppression", "ultimately lead to suppression of", "lead to suppression of cytokine", "to suppression of cytokine production", "suppression of cytokine production in", "of cytokine production in several", "cytokine production in several types", "production in several types of", "in several types of immune", "several types of immune cells", "types of immune cells resulting", "of immune cells resulting in", "immune cells resulting in reduced", "cells resulting in reduced inflammation." ] }, { "record_id": "GLY_000594_1_1188", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9012546", "r hsa", "hsa 9012546", "r hsa 9012546" ] }, { "record_id": "GLY_000594_1_1188", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 18", "18 signaling", "interleukin 18 signaling", "pro il18", "is a", "a pleiotropic", "pleiotropic and", "and pro", "pro inflammatory", "inflammatory cytokine.", "cytokine. it", "it belongs", "belongs to", "to the", "the interleukin", "interleukin 1", "il1 superfamily", "alboni et", "et al.", "al. 2010", "krumm et", "al. 2017", "dinarello 1999", "1999 .", ". il18", "il18 is", "is synthesized", "synthesized as", "as an", "an inactive", "inactive 24", "24 kda", "kda precursor", "precursor protein", "protein that", "that is", "is cleaved", "cleaved by", "by extracellular", "extracellular proteases", "proteases such", "such as", "as caspase", "caspase 1", "protease 3", "serine protease", "elastase or", "or cathepsin", "cathepsin g", "fantuzzi &", "& dinarello", "gracie et", "al. 2004", "sugawara et", "al. 2001", "forming an", "an 18", "18 kda", "kda mature", "mature protein", "arend et", "al. 2008", "akita et", "al. 1997", "fantuzzi et", "al. 1998", "ghayur et", "gu et", "ushio et", "al. 1996", "1996 .", ".
              il18", "
              il18 also", "also occurs", "occurs as", "as a", "a short", "short isoform", "the result", "result of", "of an", "an alternative", "alternative splicing", "splicing event", "event that", "that removes", "removes 57", "57 bp/19", "bp/19 aa", "conti et", "yang et", "al. 2005", "2005 .", ". this", "this short", "isoform has", "has a", "a modest", "modest synergistic", "synergistic action", "action with", "with the", "the il18", "il18 canonical", "canonical active", "active form.", "form. the", "il18 receptor", "1 receptor/toll", "receptor/toll like", "like receptor", "receptor superfamily.", "superfamily. it", "it consists", "consists of", "of two", "two subunits", "18 receptor", "receptor 1", "il 18r\u03b1", "il 1r5", "and interleukin", "receptor accessory", "accessory protein", "il 18r\u03b2", "18r\u03b2 il", "il 18racp", "il 18rii", "18rii or", "or il", "il 1r7", "1r7 .", ". both", "both subunits", "subunits have", "have three", "three extracellular", "extracellular immunoglobulin", "immunoglobulin like", "like domains", "domains and", "and one", "one intracellular", "intracellular toll/il", "toll/il 1", "1 receptor", "o'neill &", "dinarello 2000", "sims 2002", "2002 .", ". it", "it is", "is believed", "believed that", "that il18", "il18 binds", "binds first", "first to", "to il18r1", "il18r1 and", "and later", "later recruits", "recruits il18rap", "il18rap to", "to form", "form a", "a high", "high affinity", "affinity heterotrimeric", "heterotrimeric complex", "sergi &", "& pentilla", "pentilla 2004", "al. 2009", "2009 .", "isoform of", "of il18r1", "il18r1 lacks", "lacks the", "the tir", "tir domain", "il18r1 type", "type ii", "which is", "is required", "required for", "for signaling", "leading to", "the suggestion", "suggestion that", "that il18r1", "ii is", "a decoy", "decoy receptor", "colotta et", "al. 1994", "1994 .", ". a", "a truncated", "truncated form", "form of", "of il18rap", "il18rap containing", "containing only", "only one", "one of", "of the", "the three", "three immunoglobulin", "immunoglobulin domains", "domains stabilizes", "stabilizes il18", "il18 binding", "binding to", "il18r1 but", "but prevents", "prevents signaling.
              il", "signaling.
              il 18", "18 binding", "binding protein", "a 38", "38 kda", "kda soluble", "soluble protein", "is another", "another negative", "negative regulator", "regulator of", "of il18", "il18 signaling.", "signaling. it", "it has", "has some", "some sequence", "sequence homology", "homology with", "with il18r1", "im et", "al. 2002", "kim et", "novick et", "al. 1999", ". il18bp", "il18bp binds", "binds with", "with high", "affinity to", "to mature", "mature il18", "preventing its", "its interaction", "interaction with", "with il18r1.", "il18r1. several", "several isoforms", "isoforms il18bp", "il18bp have", "have been", "been described", "al. 2000", "2000 .", ". interleukin", "interleukin 37", "il 1f7", "il18 signaling", "is able", "able to", "to bind", "bind il18bp", "il18bp and", "and il18rap", "il18rap preventing", "preventing signaling", "bufler et", "et al.2002", "pan et", "kumar et", "2002 .
              il18", ".
              il18 stimulates", "stimulates interferon", "interferon gamma", "ifn \u03b3", "production from", "from t", "t helper", "helper lymphocytes", "lymphocytes cells", "and macrophages", "macrophages and", "and enhances", "enhances the", "the cytotoxicity", "cytotoxicity of", "of natural", "natural killer", "cells. il18", "il18 stimulated", "stimulated ifng", "ifng production", "production is", "is synergistically", "synergistically amplified", "amplified by", "by other", "other th1", "th1 related", "related cytokines", "cytokines such", "as il2", "il12 and", "and il23", "boraschi &", "dinarello 2006", "park et", "al. 2007", "dinarello 2007", "dinarello &", "& fantuzzi", "fantuzzi 2003", "2003 .", "18 il18", "il18 pro", "is a pleiotropic", "a pleiotropic and", "pleiotropic and pro", "and pro inflammatory", "pro inflammatory cytokine.", "inflammatory cytokine. it", "cytokine. it belongs", "it belongs to", "belongs to the", "to the interleukin", "the interleukin 1", "1 il1", "superfamily alboni", "alboni et al.", "et al. 2010", "2010 krumm", "krumm et al.", "et al. 2017", "2017 dinarello", "dinarello 1999 .", "1999 . il18", ". il18 is", "il18 is synthesized", "is synthesized as", "synthesized as an", "as an inactive", "an inactive 24", "inactive 24 kda", "24 kda precursor", "kda precursor protein", "precursor protein that", "protein that is", "that is cleaved", "is cleaved by", "cleaved by extracellular", "by extracellular proteases", "extracellular proteases such", "proteases such as", "such as caspase", "as caspase 1", "1 protease", "3 serine", "protease elastase", "elastase or cathepsin", "or cathepsin g", "g fantuzzi", "fantuzzi & dinarello", "& dinarello 1999", "1999 gracie", "gracie et al.", "et al. 2004", "2004 sugawara", "sugawara et al.", "et al. 2001", "forming an 18", "an 18 kda", "18 kda mature", "kda mature protein", "protein arend", "arend et al.", "et al. 2008", "2008 akita", "akita et al.", "et al. 1997", "1997 fantuzzi", "fantuzzi et al.", "et al. 1998", "1998 ghayur", "ghayur et al.", "1997 gu", "gu et al.", "1997 ushio", "ushio et al.", "et al. 1996", "al. 1996 .", "1996 .
              il18", ".
              il18 also", "
              il18 also occurs", "also occurs as", "occurs as a", "as a short", "a short isoform", "isoform the", "the result of", "result of an", "of an alternative", "an alternative splicing", "alternative splicing event", "splicing event that", "event that removes", "that removes 57", "removes 57 bp/19", "57 bp/19 aa", "aa il18alpha", "conti et al.", "1997 yang", "yang et al.", "et al. 2005", "al. 2005 .", "2005 . this", ". this short", "this short isoform", "short isoform has", "isoform has a", "has a modest", "a modest synergistic", "modest synergistic action", "synergistic action with", "action with the", "with the il18", "the il18 canonical", "il18 canonical active", "canonical active form.", "active form. the", "form. the il18", "the il18 receptor", "receptor il18r", "il18r belongs", "interleukin 1 receptor/toll", "1 receptor/toll like", "receptor/toll like receptor", "like receptor superfamily.", "receptor superfamily. it", "superfamily. it consists", "it consists of", "consists of two", "of two subunits", "subunits interleukin", "interleukin 18 receptor", "18 receptor 1", "1 il18r1", "il18r1 il", "18r\u03b1 il1rrp1", "il1rrp1 il18r1", "1r5 and", "and interleukin 18", "18 receptor accessory", "receptor accessory protein", "protein il18rap", "il18rap il18rb", "il18rb il", "il 18r\u03b2 il", "18r\u03b2 il 18racp", "18racp il", "il 18rii or", "18rii or il", "or il 1r7", "il 1r7 .", "1r7 . both", ". both subunits", "both subunits have", "subunits have three", "have three extracellular", "three extracellular immunoglobulin", "extracellular immunoglobulin like", "immunoglobulin like domains", "like domains and", "domains and one", "and one intracellular", "one intracellular toll/il", "intracellular toll/il 1", "toll/il 1 receptor", "receptor tir", "domain o'neill", "o'neill & dinarello", "& dinarello 2000", "2000 sims", "sims 2002 .", "2002 . it", ". it is", "it is believed", "is believed that", "believed that il18", "that il18 binds", "il18 binds first", "binds first to", "first to il18r1", "to il18r1 and", "il18r1 and later", "and later recruits", "later recruits il18rap", "recruits il18rap to", "il18rap to form", "to form a", "form a high", "a high affinity", "high affinity heterotrimeric", "affinity heterotrimeric complex", "complex sims", "2002 sergi", "sergi & pentilla", "& pentilla 2004", "2004 alboni", "et al. 2009", "al. 2009 .", "short isoform of", "isoform of il18r1", "of il18r1 lacks", "il18r1 lacks the", "lacks the tir", "the tir domain", "domain il18r1", "il18r1 type ii", "which is required", "is required for", "required for signaling", "signaling leading", "leading to the", "to the suggestion", "the suggestion that", "suggestion that il18r1", "that il18r1 type", "type ii is", "ii is a", "is a decoy", "a decoy receptor", "receptor colotta", "colotta et al.", "et al. 1994", "al. 1994 .", "1994 . a", ". a truncated", "a truncated form", "truncated form of", "form of il18rap", "of il18rap containing", "il18rap containing only", "containing only one", "only one of", "one of the", "of the three", "the three immunoglobulin", "three immunoglobulin domains", "immunoglobulin domains stabilizes", "domains stabilizes il18", "stabilizes il18 binding", "il18 binding to", "binding to il18r1", "to il18r1 but", "il18r1 but prevents", "but prevents signaling.
              il", "prevents signaling.
              il 18", "signaling.
              il 18 binding", "18 binding protein", "protein il18bp", "a 38 kda", "38 kda soluble", "kda soluble protein", "protein is", "is another negative", "another negative regulator", "negative regulator of", "regulator of il18", "of il18 signaling.", "il18 signaling. it", "signaling. it has", "it has some", "has some sequence", "some sequence homology", "sequence homology with", "homology with il18r1", "il18r1 im", "im et al.", "et al. 2002", "kim et al.", "2002 novick", "novick et al.", "et al. 1999", "al. 1999 .", "1999 . il18bp", ". il18bp binds", "il18bp binds with", "binds with high", "with high affinity", "high affinity to", "affinity to mature", "to mature il18", "il18 preventing", "preventing its interaction", "its interaction with", "interaction with il18r1.", "with il18r1. several", "il18r1. several isoforms", "several isoforms il18bp", "isoforms il18bp have", "il18bp have been", "have been described", "described kim", "et al. 2000", "al. 2000 .", "2000 . interleukin", ". interleukin 37", "37 il37", "il37 il", "of il18 signaling", "signaling is", "is able to", "able to bind", "to bind il18bp", "bind il18bp and", "il18bp and il18rap", "and il18rap preventing", "il18rap preventing signaling", "signaling bufler", "bufler et al.2002", "al.2002 pan", "pan et al.", "2001 kumar", "kumar et al.", "al. 2002 .
              il18", "2002 .
              il18 stimulates", ".
              il18 stimulates interferon", "stimulates interferon gamma", "gamma ifng", "ifng ifn", "\u03b3 production", "production from t", "from t helper", "t helper lymphocytes", "helper lymphocytes cells", "cells th1", "th1 and", "and macrophages and", "macrophages and enhances", "and enhances the", "enhances the cytotoxicity", "the cytotoxicity of", "cytotoxicity of natural", "of natural killer", "killer nk", "nk cells.", "cells. il18 stimulated", "il18 stimulated ifng", "stimulated ifng production", "ifng production is", "production is synergistically", "is synergistically amplified", "synergistically amplified by", "amplified by other", "by other th1", "other th1 related", "th1 related cytokines", "related cytokines such", "cytokines such as", "such as il2", "il2 il15", "il15 il12", "il12 and il23", "il23 boraschi", "boraschi & dinarello", "& dinarello 2006", "2006 park", "park et al.", "et al. 2007", "2007 dinarello", "dinarello & fantuzzi", "& fantuzzi 2003", "fantuzzi 2003 .", "interleukin 18 il18", "il18 pro il18", "pro il18 is", "il18 is a", "is a pleiotropic and", "a pleiotropic and pro", "pleiotropic and pro inflammatory", "and pro inflammatory cytokine.", "pro inflammatory cytokine. it", "inflammatory cytokine. it belongs", "cytokine. it belongs to", "it belongs to the", "belongs to the interleukin", "to the interleukin 1", "interleukin 1 il1", "1 il1 superfamily", "il1 superfamily alboni", "superfamily alboni et", "alboni et al. 2010", "al. 2010 krumm", "2010 krumm et", "krumm et al. 2017", "al. 2017 dinarello", "2017 dinarello 1999", "dinarello 1999 . il18", "1999 . il18 is", ". il18 is synthesized", "il18 is synthesized as", "is synthesized as an", "synthesized as an inactive", "as an inactive 24", "an inactive 24 kda", "inactive 24 kda precursor", "24 kda precursor protein", "kda precursor protein that", "precursor protein that is", "protein that is cleaved", "that is cleaved by", "is cleaved by extracellular", "cleaved by extracellular proteases", "by extracellular proteases such", "extracellular proteases such as", "proteases such as caspase", "such as caspase 1", "caspase 1 protease", "1 protease 3", "protease 3 serine", "3 serine protease", "serine protease elastase", "protease elastase or", "elastase or cathepsin g", "cathepsin g fantuzzi", "g fantuzzi &", "fantuzzi & dinarello 1999", "dinarello 1999 gracie", "1999 gracie et", "gracie et al. 2004", "al. 2004 sugawara", "2004 sugawara et", "sugawara et al. 2001", "2001 forming", "forming an 18 kda", "an 18 kda mature", "18 kda mature protein", "mature protein arend", "protein arend et", "arend et al. 2008", "al. 2008 akita", "2008 akita et", "akita et al. 1997", "al. 1997 fantuzzi", "1997 fantuzzi et", "fantuzzi et al. 1998", "al. 1998 ghayur", "1998 ghayur et", "ghayur et al. 1997", "al. 1997 gu", "1997 gu et", "gu et al. 1997", "al. 1997 ushio", "1997 ushio et", "ushio et al. 1996", "et al. 1996 .", "al. 1996 .
              il18", "1996 .
              il18 also", ".
              il18 also occurs", "
              il18 also occurs as", "also occurs as a", "occurs as a short", "as a short isoform", "short isoform the", "isoform the result", "the result of an", "result of an alternative", "of an alternative splicing", "an alternative splicing event", "alternative splicing event that", "splicing event that removes", "event that removes 57", "that removes 57 bp/19", "removes 57 bp/19 aa", "bp/19 aa il18alpha", "il18alpha conti", "conti et al. 1997", "al. 1997 yang", "1997 yang et", "yang et al. 2005", "et al. 2005 .", "al. 2005 . this", "2005 . this short", ". this short isoform", "this short isoform has", "short isoform has a", "isoform has a modest", "has a modest synergistic", "a modest synergistic action", "modest synergistic action with", "synergistic action with the", "action with the il18", "with the il18 canonical", "the il18 canonical active", "il18 canonical active form.", "canonical active form. the", "active form. the il18", "form. the il18 receptor", "il18 receptor il18r", "il18r belongs to", "the interleukin 1 receptor/toll", "interleukin 1 receptor/toll like", "1 receptor/toll like receptor", "receptor/toll like receptor superfamily.", "like receptor superfamily. it", "receptor superfamily. it consists", "superfamily. it consists of", "it consists of two", "consists of two subunits", "two subunits interleukin", "subunits interleukin 18", "interleukin 18 receptor 1", "receptor 1 il18r1", "il18r1 il 18r\u03b1", "il 18r\u03b1 il1rrp1", "il18r1 il 1r5", "il 1r5 and", "1r5 and interleukin", "and interleukin 18 receptor", "interleukin 18 receptor accessory", "18 receptor accessory protein", "accessory protein il18rap", "il18rb il 18r\u03b2", "il 18r\u03b2 il 18racp", "il 18racp il", "18racp il 18rii", "il 18rii or il", "18rii or il 1r7", "or il 1r7 .", "il 1r7 . both", "1r7 . both subunits", ". both subunits have", "both subunits have three", "subunits have three extracellular", "have three extracellular immunoglobulin", "three extracellular immunoglobulin like", "extracellular immunoglobulin like domains", "immunoglobulin like domains and", "like domains and one", "domains and one intracellular", "and one intracellular toll/il", "one intracellular toll/il 1", "intracellular toll/il 1 receptor", "1 receptor tir", "domain o'neill &", "o'neill & dinarello 2000", "dinarello 2000 sims", "2000 sims 2002", "sims 2002 . it", "2002 . it is", ". it is believed", "it is believed that", "is believed that il18", "believed that il18 binds", "that il18 binds first", "il18 binds first to", "binds first to il18r1", "first to il18r1 and", "to il18r1 and later", "il18r1 and later recruits", "and later recruits il18rap", "later recruits il18rap to", "recruits il18rap to form", "il18rap to form a", "to form a high", "form a high affinity", "a high affinity heterotrimeric", "high affinity heterotrimeric complex", "heterotrimeric complex sims", "complex sims 2002", "sims 2002 sergi", "2002 sergi &", "sergi & pentilla 2004", "pentilla 2004 alboni", "2004 alboni et", "alboni et al. 2009", "et al. 2009 .", "2009 . a", ". a short", "a short isoform of", "short isoform of il18r1", "isoform of il18r1 lacks", "of il18r1 lacks the", "il18r1 lacks the tir", "lacks the tir domain", "tir domain il18r1", "domain il18r1 type", "ii alboni", "2009 which", "which is required for", "is required for signaling", "for signaling leading", "signaling leading to", "leading to the suggestion", "to the suggestion that", "the suggestion that il18r1", "suggestion that il18r1 type", "that il18r1 type ii", "il18r1 type ii is", "type ii is a", "ii is a decoy", "is a decoy receptor", "decoy receptor colotta", "receptor colotta et", "colotta et al. 1994", "et al. 1994 .", "al. 1994 . a", "1994 . a truncated", ". a truncated form", "a truncated form of", "truncated form of il18rap", "form of il18rap containing", "of il18rap containing only", "il18rap containing only one", "containing only one of", "only one of the", "one of the three", "of the three immunoglobulin", "the three immunoglobulin domains", "three immunoglobulin domains stabilizes", "immunoglobulin domains stabilizes il18", "domains stabilizes il18 binding", "stabilizes il18 binding to", "il18 binding to il18r1", "binding to il18r1 but", "to il18r1 but prevents", "il18r1 but prevents signaling.
              il", "but prevents signaling.
              il 18", "prevents signaling.
              il 18 binding", "signaling.
              il 18 binding protein", "binding protein il18bp", "il18bp a", "a 38 kda soluble", "38 kda soluble protein", "soluble protein is", "protein is another", "is another negative regulator", "another negative regulator of", "negative regulator of il18", "regulator of il18 signaling.", "of il18 signaling. it", "il18 signaling. it has", "signaling. it has some", "it has some sequence", "has some sequence homology", "some sequence homology with", "sequence homology with il18r1", "with il18r1 im", "il18r1 im et", "im et al. 2002", "2002 kim", "kim et al. 2002", "al. 2002 novick", "2002 novick et", "novick et al. 1999", "et al. 1999 .", "al. 1999 . il18bp", "1999 . il18bp binds", ". il18bp binds with", "il18bp binds with high", "binds with high affinity", "with high affinity to", "high affinity to mature", "affinity to mature il18", "mature il18 preventing", "il18 preventing its", "preventing its interaction with", "its interaction with il18r1.", "interaction with il18r1. several", "with il18r1. several isoforms", "il18r1. several isoforms il18bp", "several isoforms il18bp have", "isoforms il18bp have been", "il18bp have been described", "been described kim", "described kim et", "kim et al. 2000", "et al. 2000 .", "al. 2000 . interleukin", "2000 . interleukin 37", "interleukin 37 il37", "il37 il 1f7", "1f7 another", "regulator of il18 signaling", "il18 signaling is", "signaling is able", "is able to bind", "able to bind il18bp", "to bind il18bp and", "bind il18bp and il18rap", "il18bp and il18rap preventing", "and il18rap preventing signaling", "preventing signaling bufler", "signaling bufler et", "et al.2002 pan", "al.2002 pan et", "pan et al. 2001", "al. 2001 kumar", "2001 kumar et", "kumar et al. 2002", "et al. 2002 .
              il18", "al. 2002 .
              il18 stimulates", "2002 .
              il18 stimulates interferon", ".
              il18 stimulates interferon gamma", "interferon gamma ifng", "ifng ifn \u03b3", "ifn \u03b3 production", "\u03b3 production from", "production from t helper", "from t helper lymphocytes", "t helper lymphocytes cells", "lymphocytes cells th1", "th1 and macrophages", "and macrophages and enhances", "macrophages and enhances the", "and enhances the cytotoxicity", "enhances the cytotoxicity of", "the cytotoxicity of natural", "cytotoxicity of natural killer", "natural killer nk", "nk cells. il18", "cells. il18 stimulated ifng", "il18 stimulated ifng production", "stimulated ifng production is", "ifng production is synergistically", "production is synergistically amplified", "is synergistically amplified by", "synergistically amplified by other", "amplified by other th1", "by other th1 related", "other th1 related cytokines", "th1 related cytokines such", "related cytokines such as", "cytokines such as il2", "as il2 il15", "il15 il12 and", "and il23 boraschi", "il23 boraschi &", "boraschi & dinarello 2006", "dinarello 2006 park", "2006 park et", "park et al. 2007", "al. 2007 dinarello", "2007 dinarello 2007", "dinarello 2007 dinarello", "2007 dinarello &", "dinarello & fantuzzi 2003", "& fantuzzi 2003 .", "18 il18 pro", "pro il18 is a", "il18 is a pleiotropic", "is a pleiotropic and pro", "a pleiotropic and pro inflammatory", "pleiotropic and pro inflammatory cytokine.", "and pro inflammatory cytokine. it", "pro inflammatory cytokine. it belongs", "inflammatory cytokine. it belongs to", "cytokine. it belongs to the", "it belongs to the interleukin", "belongs to the interleukin 1", "the interleukin 1 il1", "interleukin 1 il1 superfamily", "il1 superfamily alboni et", "superfamily alboni et al.", "et al. 2010 krumm", "al. 2010 krumm et", "2010 krumm et al.", "et al. 2017 dinarello", "al. 2017 dinarello 1999", "2017 dinarello 1999 .", "dinarello 1999 . il18 is", "1999 . il18 is synthesized", ". il18 is synthesized as", "il18 is synthesized as an", "is synthesized as an inactive", "synthesized as an inactive 24", "as an inactive 24 kda", "an inactive 24 kda precursor", "inactive 24 kda precursor protein", "24 kda precursor protein that", "kda precursor protein that is", "precursor protein that is cleaved", "protein that is cleaved by", "that is cleaved by extracellular", "is cleaved by extracellular proteases", "cleaved by extracellular proteases such", "by extracellular proteases such as", "extracellular proteases such as caspase", "proteases such as caspase 1", "as caspase 1 protease", "caspase 1 protease 3", "protease 3 serine protease", "serine protease elastase or", "protease elastase or cathepsin", "or cathepsin g fantuzzi", "cathepsin g fantuzzi &", "g fantuzzi & dinarello", "& dinarello 1999 gracie", "dinarello 1999 gracie et", "1999 gracie et al.", "et al. 2004 sugawara", "al. 2004 sugawara et", "2004 sugawara et al.", "al. 2001 forming", "2001 forming an", "forming an 18 kda mature", "an 18 kda mature protein", "kda mature protein arend", "mature protein arend et", "protein arend et al.", "et al. 2008 akita", "al. 2008 akita et", "2008 akita et al.", "et al. 1997 fantuzzi", "al. 1997 fantuzzi et", "1997 fantuzzi et al.", "et al. 1998 ghayur", "al. 1998 ghayur et", "1998 ghayur et al.", "et al. 1997 gu", "al. 1997 gu et", "1997 gu et al.", "et al. 1997 ushio", "al. 1997 ushio et", "1997 ushio et al.", "ushio et al. 1996 .", "et al. 1996 .
              il18", "al. 1996 .
              il18 also", "1996 .
              il18 also occurs", ".
              il18 also occurs as", "
              il18 also occurs as a", "also occurs as a short", "occurs as a short isoform", "a short isoform the", "short isoform the result", "isoform the result of", "the result of an alternative", "result of an alternative splicing", "of an alternative splicing event", "an alternative splicing event that", "alternative splicing event that removes", "splicing event that removes 57", "event that removes 57 bp/19", "that removes 57 bp/19 aa", "57 bp/19 aa il18alpha", "il18alpha conti et", "et al. 1997 yang", "al. 1997 yang et", "1997 yang et al.", "yang et al. 2005 .", "et al. 2005 . this", "al. 2005 . this short", "2005 . this short isoform", ". this short isoform has", "this short isoform has a", "short isoform has a modest", "isoform has a modest synergistic", "has a modest synergistic action", "a modest synergistic action with", "modest synergistic action with the", "synergistic action with the il18", "action with the il18 canonical", "with the il18 canonical active", "the il18 canonical active form.", "il18 canonical active form. the", "canonical active form. the il18", "active form. the il18 receptor", "the il18 receptor il18r", "receptor il18r belongs", "il18r belongs to the", "to the interleukin 1 receptor/toll", "the interleukin 1 receptor/toll like", "interleukin 1 receptor/toll like receptor", "1 receptor/toll like receptor superfamily.", "receptor/toll like receptor superfamily. it", "like receptor superfamily. it consists", "receptor superfamily. it consists of", "superfamily. it consists of two", "it consists of two subunits", "of two subunits interleukin", "two subunits interleukin 18", "subunits interleukin 18 receptor", "18 receptor 1 il18r1", "1 il18r1 il", "18r\u03b1 il1rrp1 il18r1", "il1rrp1 il18r1 il", "il 1r5 and interleukin", "1r5 and interleukin 18", "and interleukin 18 receptor accessory", "interleukin 18 receptor accessory protein", "receptor accessory protein il18rap", "protein il18rap il18rb", "il18rap il18rb il", "il18rb il 18r\u03b2 il", "18r\u03b2 il 18racp il", "il 18racp il 18rii", "18racp il 18rii or", "il 18rii or il 1r7", "18rii or il 1r7 .", "or il 1r7 . both", "il 1r7 . both subunits", "1r7 . both subunits have", ". both subunits have three", "both subunits have three extracellular", "subunits have three extracellular immunoglobulin", "have three extracellular immunoglobulin like", "three extracellular immunoglobulin like domains", "extracellular immunoglobulin like domains and", "immunoglobulin like domains and one", "like domains and one intracellular", "domains and one intracellular toll/il", "and one intracellular toll/il 1", "one intracellular toll/il 1 receptor", "toll/il 1 receptor tir", "receptor tir domain", "tir domain o'neill", "domain o'neill & dinarello", "& dinarello 2000 sims", "dinarello 2000 sims 2002", "2000 sims 2002 .", "sims 2002 . it is", "2002 . it is believed", ". it is believed that", "it is believed that il18", "is believed that il18 binds", "believed that il18 binds first", "that il18 binds first to", "il18 binds first to il18r1", "binds first to il18r1 and", "first to il18r1 and later", "to il18r1 and later recruits", "il18r1 and later recruits il18rap", "and later recruits il18rap to", "later recruits il18rap to form", "recruits il18rap to form a", "il18rap to form a high", "to form a high affinity", "form a high affinity heterotrimeric", "a high affinity heterotrimeric complex", "affinity heterotrimeric complex sims", "heterotrimeric complex sims 2002", "sims 2002 sergi &", "2002 sergi & pentilla", "& pentilla 2004 alboni", "pentilla 2004 alboni et", "2004 alboni et al.", "alboni et al. 2009 .", "al. 2009 . a", "2009 . a short", ". a short isoform", "a short isoform of il18r1", "short isoform of il18r1 lacks", "isoform of il18r1 lacks the", "of il18r1 lacks the tir", "il18r1 lacks the tir domain", "the tir domain il18r1", "tir domain il18r1 type", "domain il18r1 type ii", "type ii alboni", "ii alboni et", "al. 2009 which", "2009 which is", "which is required for signaling", "required for signaling leading", "for signaling leading to", "signaling leading to the", "leading to the suggestion that", "to the suggestion that il18r1", "the suggestion that il18r1 type", "suggestion that il18r1 type ii", "that il18r1 type ii is", "il18r1 type ii is a", "type ii is a decoy", "ii is a decoy receptor", "a decoy receptor colotta", "decoy receptor colotta et", "receptor colotta et al.", "colotta et al. 1994 .", "et al. 1994 . a", "al. 1994 . a truncated", "1994 . a truncated form", ". a truncated form of", "a truncated form of il18rap", "truncated form of il18rap containing", "form of il18rap containing only", "of il18rap containing only one", "il18rap containing only one of", "containing only one of the", "only one of the three", "one of the three immunoglobulin", "of the three immunoglobulin domains", "the three immunoglobulin domains stabilizes", "three immunoglobulin domains stabilizes il18", "immunoglobulin domains stabilizes il18 binding", "domains stabilizes il18 binding to", "stabilizes il18 binding to il18r1", "il18 binding to il18r1 but", "binding to il18r1 but prevents", "to il18r1 but prevents signaling.
              il", "il18r1 but prevents signaling.
              il 18", "but prevents signaling.
              il 18 binding", "prevents signaling.
              il 18 binding protein", "18 binding protein il18bp", "il18bp a 38", "a 38 kda soluble protein", "kda soluble protein is", "soluble protein is another", "protein is another negative", "is another negative regulator of", "another negative regulator of il18", "negative regulator of il18 signaling.", "regulator of il18 signaling. it", "of il18 signaling. it has", "il18 signaling. it has some", "signaling. it has some sequence", "it has some sequence homology", "has some sequence homology with", "some sequence homology with il18r1", "homology with il18r1 im", "with il18r1 im et", "il18r1 im et al.", "al. 2002 kim", "2002 kim et", "et al. 2002 novick", "al. 2002 novick et", "2002 novick et al.", "novick et al. 1999 .", "et al. 1999 . il18bp", "al. 1999 . il18bp binds", "1999 . il18bp binds with", ". il18bp binds with high", "il18bp binds with high affinity", "binds with high affinity to", "with high affinity to mature", "high affinity to mature il18", "to mature il18 preventing", "mature il18 preventing its", "il18 preventing its interaction", "preventing its interaction with il18r1.", "its interaction with il18r1. several", "interaction with il18r1. several isoforms", "with il18r1. several isoforms il18bp", "il18r1. several isoforms il18bp have", "several isoforms il18bp have been", "isoforms il18bp have been described", "have been described kim", "been described kim et", "described kim et al.", "kim et al. 2000 .", "et al. 2000 . interleukin", "al. 2000 . interleukin 37", ". interleukin 37 il37", "37 il37 il", "il 1f7 another", "1f7 another negative", "negative regulator of il18 signaling", "of il18 signaling is", "il18 signaling is able", "signaling is able to", "is able to bind il18bp", "able to bind il18bp and", "to bind il18bp and il18rap", "bind il18bp and il18rap preventing", "il18bp and il18rap preventing signaling", "il18rap preventing signaling bufler", "preventing signaling bufler et", "signaling bufler et al.2002", "bufler et al.2002 pan", "et al.2002 pan et", "al.2002 pan et al.", "et al. 2001 kumar", "al. 2001 kumar et", "2001 kumar et al.", "kumar et al. 2002 .
              il18", "et al. 2002 .
              il18 stimulates", "al. 2002 .
              il18 stimulates interferon", "2002 .
              il18 stimulates interferon gamma", "stimulates interferon gamma ifng", "gamma ifng ifn", "ifn \u03b3 production from", "\u03b3 production from t", "production from t helper lymphocytes", "from t helper lymphocytes cells", "helper lymphocytes cells th1", "cells th1 and", "th1 and macrophages and", "and macrophages and enhances the", "macrophages and enhances the cytotoxicity", "and enhances the cytotoxicity of", "enhances the cytotoxicity of natural", "the cytotoxicity of natural killer", "of natural killer nk", "killer nk cells.", "nk cells. il18 stimulated", "cells. il18 stimulated ifng production", "il18 stimulated ifng production is", "stimulated ifng production is synergistically", "ifng production is synergistically amplified", "production is synergistically amplified by", "is synergistically amplified by other", "synergistically amplified by other th1", "amplified by other th1 related", "by other th1 related cytokines", "other th1 related cytokines such", "th1 related cytokines such as", "related cytokines such as il2", "such as il2 il15", "il2 il15 il12", "il15 il12 and il23", "il12 and il23 boraschi", "and il23 boraschi &", "il23 boraschi & dinarello", "& dinarello 2006 park", "dinarello 2006 park et", "2006 park et al.", "et al. 2007 dinarello", "al. 2007 dinarello 2007", "dinarello 2007 dinarello &", "2007 dinarello & fantuzzi", "dinarello & fantuzzi 2003 ." ] }, { "record_id": "GLY_000594_1_1189", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013508", "r hsa", "hsa 9013508", "r hsa 9013508" ] }, { "record_id": "GLY_000594_1_1189", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "notch3 intracellular", "intracellular domain", "domain regulates", "regulates transcription", "notch3 intracellular domain", "intracellular domain regulates", "domain regulates transcription", "notch3 intracellular domain regulates", "intracellular domain regulates transcription", "notch3 intracellular domain regulates transcription", "in the", "the nucleus", "nicd3 forms", "forms a", "a complex", "complex with", "with rbpj", "and maml", "proteins maml1", "maml2 or", "or maml3", "possibly also", "also mamld1", "mamld1 .", ". nicd3:rbpj:maml", "nicd3:rbpj:maml complex", "also known", "known as", "as the", "the notch3", "notch3 coactivator", "coactivator complex", "activates transcription", "transcription from", "from rbpj", "rbpj binding", "binding promoter", "promoter elements", "lin et", "et al.", "al. 2002", "2002 .", ". while", "while notch1", "notch1 prefers", "prefers paired", "paired rbpj", "binding sites", "notch3 preferentially", "preferentially binds", "binds to", "to single", "single rbpj", "ong et", "al. 2006", "2006 .


              notch3", ".


              notch3 coactivator", "complex induces", "induces transcription", "transcription of", "of the", "the well", "well established", "established notch", "notch target", "target genes", "genes hes1", "boelens et", "al. 2014", "maier and", "and gessler", "gessler 2000", "geimer le", "le lay", "lay et", "lin te", "te al.", "shimizu et", "and hey2", "wang et", "2002 .

              notch3", ".

              notch3 positively", "positively regulates", "the pre", "pre t", "t cell", "cell receptor", "receptor alpha", "alpha chain", "commonly known", "as pt", "pt alpha", "alpha or", "or pre", "pre tcralpha", "talora et", "al. 2003", "bellavia et", "al. 2007", "2007 .", ". ik1", "splicing isoform", "isoform of", "the transcription", "transcription factor", "factor ikaros", "competes with", "rbpj for", "for binding", "binding to", "to the", "the ptcra", "ptcra promoter", "promoter and", "and inhibits", "inhibits ptcra", "ptcra transcription.", "transcription. notch3", "through pre", "pre tcr", "tcr signaling", "stimulates expression", "expression of", "the rna", "rna binding", "binding protein", "protein hud", "which promotes", "promotes splicing", "splicing of", "of ikzf1", "ikzf1 into", "into dominant", "dominant negative", "negative isoforms.", "isoforms. these", "these dominant", "negative isoforms", "isoforms of", "ikzf1 heterodimerize", "heterodimerize with", "with ik1", "preventing its", "its binding", "to target", "target dna", "dna sequences", "sequences and", "and thus", "thus contributing", "contributing to", "to sustained", "sustained transcription", "of ptcra", "reviewed by", "by bellavia", "gulino and", "and screpanti", "screpanti 2007", "2007 .

              notch3", ".

              notch3 triggered", "triggered pre", "signaling downregulates", "downregulates the", "the activity", "activity of", "factor tcf3", "through erk", "erk dependent", "dependent induction", "induction of", "of id1.", "id1. inhibition", "inhibition of", "of tcf3", "tcf3 mediated", "mediated transcription", "transcription downstream", "downstream of", "of notch3", "notch3 contributes", "contributes to", "to development", "development of", "of t", "cell lymphomas", "lymphomas in", "in transgenic", "transgenic mice", "mice expressing", "expressing nicd3", "2003 .", ". activation", "activation of", "of erks", "erks downstream", "notch3 stimulated", "stimulated pre", "signaling leads", "leads to", "to phosphorylation", "phosphorylation of", "factor tal1", "formation of", "the tal1:sp1", "tal1:sp1 complex", "and activation", "of cyclin", "cyclin d1", "which stimulates", "stimulates cell", "cell division", "2006 .

              notch3", ".

              notch3 signaling", "signaling can", "can activate", "activate nf", "nf kappab", "mediate transcription", "transcription either", "either indirectly", "through activation", "of pre", "or directly", "through association", "association of", "notch3 with", "with ikka.", "ikka. nfkb", "nfkb is", "is constitutively", "constitutively active", "active in", "in t", "t lymphoma", "lymphoma cells", "cells derived", "derived from", "from notch3", "notch3 transgenic", "vacca et", "2006 .

              transcription", ".

              transcription of", "the plxnd1", "plxnd1 gene", "encoding the", "the semaphorin", "semaphorin receptor", "receptor plexin", "plexin d1", "is directly", "directly stimulated", "stimulated by", "by notch1", "notch1 and", "and notch3", "coactivator complexes.", "complexes. plxnd1", "plxnd1 is", "is involved", "involved in", "in neuronal", "neuronal migration", "migration and", "and cancer", "cancer cell", "cell invasiveness", "rehman et", "al. 2016", "2016 .", ". expression", "of fabp7", "in radial", "radial glia", "glia is", "is positively", "positively regulated", "regulated by", "notch3 during", "during neuronal", "anthony et", "al. 2005", "keilani and", "and sugaya", "sugaya 2008", "2008 .


              notch3", ".


              notch3 gene", "gene is", "is frequently", "frequently amplified", "amplified in", "in ovarian", "ovarian cancer", "park et", "2006 .", ". notch3", "complex directly", "directly stimulates", "stimulates dlgap5", "dlgap5 transcription.", "transcription. dlgap5", "dlgap5 is", "in g2/m", "g2/m transition", "transition and", "and is", "is overexpressed", "overexpressed in", "cancer cells.", "chen et", "al. 2012", "2012 .", ". another", "another gene", "gene overexpressed", "cancer whose", "whose transcription", "transcription is", "by notch3", "notch3 is", "is pbx1", "al. 2008", "2008 .", ". the", "stimulates wwc1", "wwc1 gene", "gene transcription.", "transcription. wwc1", "gene encodes", "encodes protein", "protein kibra", "in hippo", "hippo signaling.", "signaling. notch3", "notch3 mediated", "mediated induction", "of wwc1", "regulates hippo", "hippo signaling", "signaling and", "inhibits epithelial", "epithelial to", "to mesenchymal", "mesenchymal transition", "in triple", "triple negative", "negative breast", "breast cancer", "cancer cells", "zhang et", "2016 .
              ", "in the nucleus", "nucleus nicd3", "nicd3 forms a", "forms a complex", "a complex with", "complex with rbpj", "rbpj cbf1", "cbf1 csl", "csl and", "maml mastermind", "mastermind proteins", "maml1 maml2", "maml2 or maml3", "maml3 possibly", "possibly also mamld1", "also mamld1 .", "mamld1 . nicd3:rbpj:maml", ". nicd3:rbpj:maml complex", "complex also", "also known as", "known as the", "as the notch3", "the notch3 coactivator", "notch3 coactivator complex", "complex activates", "activates transcription from", "transcription from rbpj", "from rbpj binding", "rbpj binding promoter", "binding promoter elements", "elements lin", "lin et al.", "et al. 2002", "al. 2002 .", "2002 . while", ". while notch1", "while notch1 prefers", "notch1 prefers paired", "prefers paired rbpj", "paired rbpj binding", "rbpj binding sites", "sites notch3", "notch3 preferentially binds", "preferentially binds to", "binds to single", "to single rbpj", "single rbpj binding", "sites ong", "ong et al.", "et al. 2006", "al. 2006 .


              notch3", "2006 .


              notch3 coactivator", ".


              notch3 coactivator complex", "coactivator complex induces", "complex induces transcription", "induces transcription of", "transcription of the", "of the well", "the well established", "well established notch", "established notch target", "notch target genes", "target genes hes1", "hes1 lin", "2002 boelens", "boelens et al.", "et al. 2014", "heyl maier", "maier and gessler", "and gessler 2000", "2000 geimer", "geimer le lay", "le lay et", "lay et al.", "hes5 lin", "lin te al.", "te al. 2002", "2002 shimizu", "shimizu et al.", "hey2 wang", "wang et al.", "al. 2002 .

              notch3", "2002 .

              notch3 positively", ".

              notch3 positively regulates", "positively regulates transcription", "regulates transcription of", "of the pre", "the pre t", "pre t cell", "t cell receptor", "cell receptor alpha", "receptor alpha chain", "chain ptcra", "ptcra commonly", "commonly known as", "known as pt", "as pt alpha", "pt alpha or", "alpha or pre", "or pre tcralpha", "talora et al.", "et al. 2003", "2003 bellavia", "bellavia et al.", "et al. 2007", "al. 2007 .", "2007 . ik1", "ik1 splicing", "splicing isoform of", "isoform of the", "of the transcription", "the transcription factor", "transcription factor ikaros", "ikaros ikzf1", "competes with rbpj", "with rbpj for", "rbpj for binding", "for binding to", "binding to the", "to the ptcra", "the ptcra promoter", "ptcra promoter and", "promoter and inhibits", "and inhibits ptcra", "inhibits ptcra transcription.", "ptcra transcription. notch3", "notch3 through", "through pre tcr", "pre tcr signaling", "signaling stimulates", "stimulates expression of", "expression of the", "of the rna", "the rna binding", "rna binding protein", "binding protein hud", "hud which", "which promotes splicing", "promotes splicing of", "splicing of ikzf1", "of ikzf1 into", "ikzf1 into dominant", "into dominant negative", "dominant negative isoforms.", "negative isoforms. these", "isoforms. these dominant", "these dominant negative", "dominant negative isoforms", "negative isoforms of", "isoforms of ikzf1", "of ikzf1 heterodimerize", "ikzf1 heterodimerize with", "heterodimerize with ik1", "ik1 preventing", "preventing its binding", "its binding to", "binding to target", "to target dna", "target dna sequences", "dna sequences and", "sequences and thus", "and thus contributing", "thus contributing to", "contributing to sustained", "to sustained transcription", "sustained transcription of", "transcription of ptcra", "ptcra bellavia", "2007 reviewed", "reviewed by bellavia", "bellavia mecarrozzi", "mecarrozzi campese", "campese grazioli", "grazioli gulino", "gulino and screpanti", "and screpanti 2007", "screpanti 2007 .

              notch3", "2007 .

              notch3 triggered", ".

              notch3 triggered pre", "triggered pre tcr", "tcr signaling downregulates", "signaling downregulates the", "downregulates the activity", "the activity of", "activity of the", "transcription factor tcf3", "tcf3 e2a", "through erk dependent", "erk dependent induction", "dependent induction of", "induction of id1.", "of id1. inhibition", "id1. inhibition of", "inhibition of tcf3", "of tcf3 mediated", "tcf3 mediated transcription", "mediated transcription downstream", "transcription downstream of", "downstream of notch3", "of notch3 contributes", "notch3 contributes to", "contributes to development", "to development of", "development of t", "of t cell", "t cell lymphomas", "cell lymphomas in", "lymphomas in transgenic", "in transgenic mice", "transgenic mice expressing", "mice expressing nicd3", "nicd3 talora", "al. 2003 .", "2003 . activation", ". activation of", "activation of erks", "of erks downstream", "erks downstream of", "of notch3 stimulated", "notch3 stimulated pre", "stimulated pre tcr", "tcr signaling leads", "signaling leads to", "leads to phosphorylation", "to phosphorylation of", "phosphorylation of the", "transcription factor tal1", "tal1 formation", "formation of the", "of the tal1:sp1", "the tal1:sp1 complex", "complex and", "and activation of", "activation of cyclin", "of cyclin d1", "d1 ccnd1", "ccnd1 transcription", "transcription which", "which stimulates cell", "stimulates cell division", "division talora", "al. 2006 .

              notch3", "2006 .

              notch3 signaling", ".

              notch3 signaling can", "signaling can activate", "can activate nf", "activate nf kappab", "kappab nfkb", "nfkb mediate", "mediate transcription either", "transcription either indirectly", "indirectly through", "through activation of", "activation of pre", "of pre tcr", "signaling or", "directly through", "through association of", "association of notch3", "of notch3 with", "notch3 with ikka.", "with ikka. nfkb", "ikka. nfkb is", "nfkb is constitutively", "is constitutively active", "constitutively active in", "active in t", "in t lymphoma", "t lymphoma cells", "lymphoma cells derived", "cells derived from", "derived from notch3", "from notch3 transgenic", "notch3 transgenic mice", "mice vacca", "vacca et al.", "al. 2006 .

              transcription", "2006 .

              transcription of", ".

              transcription of the", "of the plxnd1", "the plxnd1 gene", "gene encoding", "encoding the semaphorin", "the semaphorin receptor", "semaphorin receptor plexin", "receptor plexin d1", "d1 is", "is directly stimulated", "directly stimulated by", "stimulated by notch1", "by notch1 and", "notch1 and notch3", "and notch3 coactivator", "notch3 coactivator complexes.", "coactivator complexes. plxnd1", "complexes. plxnd1 is", "plxnd1 is involved", "is involved in", "involved in neuronal", "in neuronal migration", "neuronal migration and", "migration and cancer", "and cancer cell", "cancer cell invasiveness", "invasiveness rehman", "rehman et al.", "et al. 2016", "al. 2016 .", "2016 . expression", ". expression of", "expression of fabp7", "fabp7 blbp", "blbp in", "in radial glia", "radial glia is", "glia is positively", "is positively regulated", "positively regulated by", "regulated by notch1", "and notch3 during", "notch3 during neuronal", "during neuronal migration", "migration anthony", "anthony et al.", "et al. 2005", "2005 keilani", "keilani and sugaya", "and sugaya 2008", "sugaya 2008 .


              notch3", "2008 .


              notch3 gene", ".


              notch3 gene is", "gene is frequently", "is frequently amplified", "frequently amplified in", "amplified in ovarian", "in ovarian cancer", "cancer park", "park et al.", "al. 2006 .", "2006 . notch3", ". notch3 coactivator", "coactivator complex directly", "complex directly stimulates", "directly stimulates dlgap5", "stimulates dlgap5 transcription.", "dlgap5 transcription. dlgap5", "transcription. dlgap5 is", "dlgap5 is involved", "involved in g2/m", "in g2/m transition", "g2/m transition and", "transition and is", "and is overexpressed", "is overexpressed in", "overexpressed in ovarian", "ovarian cancer cells.", "cells. chen", "chen et al.", "et al. 2012", "al. 2012 .", "2012 . another", ". another gene", "another gene overexpressed", "gene overexpressed in", "ovarian cancer whose", "cancer whose transcription", "whose transcription is", "transcription is directly", "stimulated by notch3", "by notch3 is", "notch3 is pbx1", "pbx1 park", "et al. 2008", "al. 2008 .", "2008 . the", ". the notch3", "directly stimulates wwc1", "stimulates wwc1 gene", "wwc1 gene transcription.", "gene transcription. wwc1", "transcription. wwc1 gene", "wwc1 gene encodes", "gene encodes protein", "encodes protein kibra", "kibra involved", "involved in hippo", "in hippo signaling.", "hippo signaling. notch3", "signaling. notch3 mediated", "notch3 mediated induction", "mediated induction of", "induction of wwc1", "wwc1 positively", "positively regulates hippo", "regulates hippo signaling", "hippo signaling and", "signaling and inhibits", "and inhibits epithelial", "inhibits epithelial to", "epithelial to mesenchymal", "to mesenchymal transition", "transition emt", "emt in", "in triple negative", "triple negative breast", "negative breast cancer", "breast cancer cells", "cells zhang", "zhang et al.", "al. 2016 .
              ", "the nucleus nicd3", "nucleus nicd3 forms", "nicd3 forms a complex", "forms a complex with", "a complex with rbpj", "with rbpj cbf1", "csl and maml", "and maml mastermind", "mastermind proteins maml1", "proteins maml1 maml2", "maml1 maml2 or", "or maml3 possibly", "maml3 possibly also", "possibly also mamld1 .", "also mamld1 . nicd3:rbpj:maml", "mamld1 . nicd3:rbpj:maml complex", "nicd3:rbpj:maml complex also", "complex also known", "also known as the", "known as the notch3", "as the notch3 coactivator", "the notch3 coactivator complex", "coactivator complex activates", "complex activates transcription", "activates transcription from rbpj", "transcription from rbpj binding", "from rbpj binding promoter", "rbpj binding promoter elements", "promoter elements lin", "elements lin et", "lin et al. 2002", "et al. 2002 .", "al. 2002 . while", "2002 . while notch1", ". while notch1 prefers", "while notch1 prefers paired", "notch1 prefers paired rbpj", "prefers paired rbpj binding", "paired rbpj binding sites", "binding sites notch3", "sites notch3 preferentially", "notch3 preferentially binds to", "preferentially binds to single", "binds to single rbpj", "to single rbpj binding", "single rbpj binding sites", "binding sites ong", "sites ong et", "ong et al. 2006", "et al. 2006 .


              notch3", "al. 2006 .


              notch3 coactivator", "2006 .


              notch3 coactivator complex", ".


              notch3 coactivator complex induces", "coactivator complex induces transcription", "complex induces transcription of", "induces transcription of the", "transcription of the well", "of the well established", "the well established notch", "well established notch target", "established notch target genes", "notch target genes hes1", "genes hes1 lin", "hes1 lin et", "al. 2002 boelens", "2002 boelens et", "boelens et al. 2014", "2014 heyl", "heyl maier and", "maier and gessler 2000", "gessler 2000 geimer", "2000 geimer le", "geimer le lay et", "le lay et al.", "lay et al. 2014", "2014 hes5", "hes5 lin te", "lin te al. 2002", "al. 2002 shimizu", "2002 shimizu et", "shimizu et al. 2002", "2002 and", "and hey2 wang", "hey2 wang et", "wang et al. 2002", "et al. 2002 .

              notch3", "al. 2002 .

              notch3 positively", "2002 .

              notch3 positively regulates", ".

              notch3 positively regulates transcription", "positively regulates transcription of", "regulates transcription of the", "transcription of the pre", "of the pre t", "the pre t cell", "pre t cell receptor", "t cell receptor alpha", "cell receptor alpha chain", "alpha chain ptcra", "ptcra commonly known", "commonly known as pt", "known as pt alpha", "as pt alpha or", "pt alpha or pre", "alpha or pre tcralpha", "tcralpha talora", "talora et al. 2003", "al. 2003 bellavia", "2003 bellavia et", "bellavia et al. 2007", "et al. 2007 .", "al. 2007 . ik1", ". ik1 splicing", "ik1 splicing isoform", "splicing isoform of the", "isoform of the transcription", "of the transcription factor", "the transcription factor ikaros", "factor ikaros ikzf1", "ikzf1 competes", "competes with rbpj for", "with rbpj for binding", "rbpj for binding to", "for binding to the", "binding to the ptcra", "to the ptcra promoter", "the ptcra promoter and", "ptcra promoter and inhibits", "promoter and inhibits ptcra", "and inhibits ptcra transcription.", "inhibits ptcra transcription. notch3", "transcription. notch3 through", "notch3 through pre", "through pre tcr signaling", "tcr signaling stimulates", "signaling stimulates expression", "stimulates expression of the", "expression of the rna", "of the rna binding", "the rna binding protein", "rna binding protein hud", "protein hud which", "hud which promotes", "which promotes splicing of", "promotes splicing of ikzf1", "splicing of ikzf1 into", "of ikzf1 into dominant", "ikzf1 into dominant negative", "into dominant negative isoforms.", "dominant negative isoforms. these", "negative isoforms. these dominant", "isoforms. these dominant negative", "these dominant negative isoforms", "dominant negative isoforms of", "negative isoforms of ikzf1", "isoforms of ikzf1 heterodimerize", "of ikzf1 heterodimerize with", "ikzf1 heterodimerize with ik1", "with ik1 preventing", "ik1 preventing its", "preventing its binding to", "its binding to target", "binding to target dna", "to target dna sequences", "target dna sequences and", "dna sequences and thus", "sequences and thus contributing", "and thus contributing to", "thus contributing to sustained", "contributing to sustained transcription", "to sustained transcription of", "sustained transcription of ptcra", "of ptcra bellavia", "ptcra bellavia et", "al. 2007 reviewed", "2007 reviewed by", "by bellavia mecarrozzi", "grazioli gulino and", "gulino and screpanti 2007", "and screpanti 2007 .

              notch3", "screpanti 2007 .

              notch3 triggered", "2007 .

              notch3 triggered pre", ".

              notch3 triggered pre tcr", "triggered pre tcr signaling", "pre tcr signaling downregulates", "tcr signaling downregulates the", "signaling downregulates the activity", "downregulates the activity of", "the activity of the", "activity of the transcription", "the transcription factor tcf3", "factor tcf3 e2a", "e2a through", "through erk dependent induction", "erk dependent induction of", "dependent induction of id1.", "induction of id1. inhibition", "of id1. inhibition of", "id1. inhibition of tcf3", "inhibition of tcf3 mediated", "of tcf3 mediated transcription", "tcf3 mediated transcription downstream", "mediated transcription downstream of", "transcription downstream of notch3", "downstream of notch3 contributes", "of notch3 contributes to", "notch3 contributes to development", "contributes to development of", "to development of t", "development of t cell", "of t cell lymphomas", "t cell lymphomas in", "cell lymphomas in transgenic", "lymphomas in transgenic mice", "in transgenic mice expressing", "transgenic mice expressing nicd3", "expressing nicd3 talora", "nicd3 talora et", "et al. 2003 .", "al. 2003 . activation", "2003 . activation of", ". activation of erks", "activation of erks downstream", "of erks downstream of", "erks downstream of notch3", "downstream of notch3 stimulated", "of notch3 stimulated pre", "notch3 stimulated pre tcr", "stimulated pre tcr signaling", "pre tcr signaling leads", "tcr signaling leads to", "signaling leads to phosphorylation", "leads to phosphorylation of", "to phosphorylation of the", "phosphorylation of the transcription", "the transcription factor tal1", "factor tal1 formation", "tal1 formation of", "formation of the tal1:sp1", "of the tal1:sp1 complex", "tal1:sp1 complex and", "complex and activation", "and activation of cyclin", "activation of cyclin d1", "cyclin d1 ccnd1", "transcription which stimulates", "which stimulates cell division", "cell division talora", "division talora et", "talora et al. 2006", "et al. 2006 .

              notch3", "al. 2006 .

              notch3 signaling", "2006 .

              notch3 signaling can", ".

              notch3 signaling can activate", "signaling can activate nf", "can activate nf kappab", "nf kappab nfkb", "nfkb mediate transcription", "mediate transcription either indirectly", "either indirectly through", "indirectly through activation", "through activation of pre", "activation of pre tcr", "of pre tcr signaling", "tcr signaling or", "signaling or directly", "or directly through", "directly through association", "through association of notch3", "association of notch3 with", "of notch3 with ikka.", "notch3 with ikka. nfkb", "with ikka. nfkb is", "ikka. nfkb is constitutively", "nfkb is constitutively active", "is constitutively active in", "constitutively active in t", "active in t lymphoma", "in t lymphoma cells", "t lymphoma cells derived", "lymphoma cells derived from", "cells derived from notch3", "derived from notch3 transgenic", "from notch3 transgenic mice", "transgenic mice vacca", "mice vacca et", "vacca et al. 2006", "et al. 2006 .

              transcription", "al. 2006 .

              transcription of", "2006 .

              transcription of the", ".

              transcription of the plxnd1", "of the plxnd1 gene", "plxnd1 gene encoding", "gene encoding the", "encoding the semaphorin receptor", "the semaphorin receptor plexin", "semaphorin receptor plexin d1", "plexin d1 is", "d1 is directly", "is directly stimulated by", "directly stimulated by notch1", "stimulated by notch1 and", "by notch1 and notch3", "notch1 and notch3 coactivator", "and notch3 coactivator complexes.", "notch3 coactivator complexes. plxnd1", "coactivator complexes. plxnd1 is", "complexes. plxnd1 is involved", "plxnd1 is involved in", "is involved in neuronal", "involved in neuronal migration", "in neuronal migration and", "neuronal migration and cancer", "migration and cancer cell", "and cancer cell invasiveness", "cell invasiveness rehman", "invasiveness rehman et", "rehman et al. 2016", "et al. 2016 .", "al. 2016 . expression", "2016 . expression of", ". expression of fabp7", "of fabp7 blbp", "blbp in radial", "in radial glia is", "radial glia is positively", "glia is positively regulated", "is positively regulated by", "positively regulated by notch1", "regulated by notch1 and", "notch1 and notch3 during", "and notch3 during neuronal", "notch3 during neuronal migration", "neuronal migration anthony", "migration anthony et", "anthony et al. 2005", "al. 2005 keilani", "2005 keilani and", "keilani and sugaya 2008", "and sugaya 2008 .


              notch3", "sugaya 2008 .


              notch3 gene", "2008 .


              notch3 gene is", ".


              notch3 gene is frequently", "gene is frequently amplified", "is frequently amplified in", "frequently amplified in ovarian", "amplified in ovarian cancer", "ovarian cancer park", "cancer park et", "park et al. 2006", "et al. 2006 .", "al. 2006 . notch3", "2006 . notch3 coactivator", ". notch3 coactivator complex", "notch3 coactivator complex directly", "coactivator complex directly stimulates", "complex directly stimulates dlgap5", "directly stimulates dlgap5 transcription.", "stimulates dlgap5 transcription. dlgap5", "dlgap5 transcription. dlgap5 is", "transcription. dlgap5 is involved", "dlgap5 is involved in", "is involved in g2/m", "involved in g2/m transition", "in g2/m transition and", "g2/m transition and is", "transition and is overexpressed", "and is overexpressed in", "is overexpressed in ovarian", "overexpressed in ovarian cancer", "in ovarian cancer cells.", "cancer cells. chen", "cells. chen et", "chen et al. 2012", "et al. 2012 .", "al. 2012 . another", "2012 . another gene", ". another gene overexpressed", "another gene overexpressed in", "gene overexpressed in ovarian", "in ovarian cancer whose", "ovarian cancer whose transcription", "cancer whose transcription is", "whose transcription is directly", "transcription is directly stimulated", "directly stimulated by notch3", "stimulated by notch3 is", "by notch3 is pbx1", "is pbx1 park", "pbx1 park et", "park et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the notch3", ". the notch3 coactivator", "complex directly stimulates wwc1", "directly stimulates wwc1 gene", "stimulates wwc1 gene transcription.", "wwc1 gene transcription. wwc1", "gene transcription. wwc1 gene", "transcription. wwc1 gene encodes", "wwc1 gene encodes protein", "gene encodes protein kibra", "protein kibra involved", "kibra involved in", "involved in hippo signaling.", "in hippo signaling. notch3", "hippo signaling. notch3 mediated", "signaling. notch3 mediated induction", "notch3 mediated induction of", "mediated induction of wwc1", "of wwc1 positively", "wwc1 positively regulates", "positively regulates hippo signaling", "regulates hippo signaling and", "hippo signaling and inhibits", "signaling and inhibits epithelial", "and inhibits epithelial to", "inhibits epithelial to mesenchymal", "epithelial to mesenchymal transition", "mesenchymal transition emt", "emt in triple", "in triple negative breast", "triple negative breast cancer", "negative breast cancer cells", "cancer cells zhang", "cells zhang et", "zhang et al. 2016", "et al. 2016 .
              ", "in the nucleus nicd3", "the nucleus nicd3 forms", "nucleus nicd3 forms a", "nicd3 forms a complex with", "forms a complex with rbpj", "complex with rbpj cbf1", "rbpj cbf1 csl", "cbf1 csl and", "maml mastermind proteins", "proteins maml1 maml2 or", "maml1 maml2 or maml3", "maml2 or maml3 possibly", "or maml3 possibly also", "maml3 possibly also mamld1", "possibly also mamld1 . nicd3:rbpj:maml", "also mamld1 . nicd3:rbpj:maml complex", ". nicd3:rbpj:maml complex also", "nicd3:rbpj:maml complex also known", "complex also known as", "also known as the notch3", "known as the notch3 coactivator", "as the notch3 coactivator complex", "notch3 coactivator complex activates", "coactivator complex activates transcription", "complex activates transcription from", "activates transcription from rbpj binding", "transcription from rbpj binding promoter", "from rbpj binding promoter elements", "binding promoter elements lin", "promoter elements lin et", "elements lin et al.", "lin et al. 2002 .", "et al. 2002 . while", "al. 2002 . while notch1", "2002 . while notch1 prefers", ". while notch1 prefers paired", "while notch1 prefers paired rbpj", "notch1 prefers paired rbpj binding", "prefers paired rbpj binding sites", "rbpj binding sites notch3", "binding sites notch3 preferentially", "sites notch3 preferentially binds", "notch3 preferentially binds to single", "preferentially binds to single rbpj", "binds to single rbpj binding", "to single rbpj binding sites", "rbpj binding sites ong", "binding sites ong et", "sites ong et al.", "ong et al. 2006 .


              notch3", "et al. 2006 .


              notch3 coactivator", "al. 2006 .


              notch3 coactivator complex", "2006 .


              notch3 coactivator complex induces", ".


              notch3 coactivator complex induces transcription", "coactivator complex induces transcription of", "complex induces transcription of the", "induces transcription of the well", "transcription of the well established", "of the well established notch", "the well established notch target", "well established notch target genes", "established notch target genes hes1", "target genes hes1 lin", "genes hes1 lin et", "hes1 lin et al.", "et al. 2002 boelens", "al. 2002 boelens et", "2002 boelens et al.", "al. 2014 heyl", "heyl maier and gessler", "and gessler 2000 geimer", "gessler 2000 geimer le", "2000 geimer le lay", "geimer le lay et al.", "le lay et al. 2014", "al. 2014 hes5", "hes5 lin te al.", "te al. 2002 shimizu", "al. 2002 shimizu et", "2002 shimizu et al.", "al. 2002 and", "2002 and hey2", "and hey2 wang et", "hey2 wang et al.", "wang et al. 2002 .

              notch3", "et al. 2002 .

              notch3 positively", "al. 2002 .

              notch3 positively regulates", "2002 .

              notch3 positively regulates transcription", ".

              notch3 positively regulates transcription of", "positively regulates transcription of the", "regulates transcription of the pre", "transcription of the pre t", "of the pre t cell", "the pre t cell receptor", "pre t cell receptor alpha", "t cell receptor alpha chain", "receptor alpha chain ptcra", "chain ptcra commonly", "ptcra commonly known as", "commonly known as pt alpha", "known as pt alpha or", "as pt alpha or pre", "pt alpha or pre tcralpha", "pre tcralpha talora", "tcralpha talora et", "et al. 2003 bellavia", "al. 2003 bellavia et", "2003 bellavia et al.", "bellavia et al. 2007 .", "et al. 2007 . ik1", "2007 . ik1 splicing", ". ik1 splicing isoform", "ik1 splicing isoform of", "splicing isoform of the transcription", "isoform of the transcription factor", "of the transcription factor ikaros", "transcription factor ikaros ikzf1", "ikzf1 competes with", "competes with rbpj for binding", "with rbpj for binding to", "rbpj for binding to the", "for binding to the ptcra", "binding to the ptcra promoter", "to the ptcra promoter and", "the ptcra promoter and inhibits", "ptcra promoter and inhibits ptcra", "promoter and inhibits ptcra transcription.", "and inhibits ptcra transcription. notch3", "ptcra transcription. notch3 through", "transcription. notch3 through pre", "notch3 through pre tcr", "pre tcr signaling stimulates", "tcr signaling stimulates expression", "signaling stimulates expression of", "stimulates expression of the rna", "expression of the rna binding", "of the rna binding protein", "the rna binding protein hud", "binding protein hud which", "protein hud which promotes", "hud which promotes splicing", "which promotes splicing of ikzf1", "promotes splicing of ikzf1 into", "splicing of ikzf1 into dominant", "of ikzf1 into dominant negative", "ikzf1 into dominant negative isoforms.", "into dominant negative isoforms. these", "dominant negative isoforms. these dominant", "negative isoforms. these dominant negative", "isoforms. these dominant negative isoforms", "these dominant negative isoforms of", "dominant negative isoforms of ikzf1", "negative isoforms of ikzf1 heterodimerize", "isoforms of ikzf1 heterodimerize with", "of ikzf1 heterodimerize with ik1", "heterodimerize with ik1 preventing", "with ik1 preventing its", "ik1 preventing its binding", "preventing its binding to target", "its binding to target dna", "binding to target dna sequences", "to target dna sequences and", "target dna sequences and thus", "dna sequences and thus contributing", "sequences and thus contributing to", "and thus contributing to sustained", "thus contributing to sustained transcription", "contributing to sustained transcription of", "to sustained transcription of ptcra", "transcription of ptcra bellavia", "of ptcra bellavia et", "ptcra bellavia et al.", "et al. 2007 reviewed", "al. 2007 reviewed by", "2007 reviewed by bellavia", "reviewed by bellavia mecarrozzi", "bellavia mecarrozzi campese", "mecarrozzi campese grazioli", "campese grazioli gulino", "grazioli gulino and screpanti", "gulino and screpanti 2007 .

              notch3", "and screpanti 2007 .

              notch3 triggered", "screpanti 2007 .

              notch3 triggered pre", "2007 .

              notch3 triggered pre tcr", ".

              notch3 triggered pre tcr signaling", "triggered pre tcr signaling downregulates", "pre tcr signaling downregulates the", "tcr signaling downregulates the activity", "signaling downregulates the activity of", "downregulates the activity of the", "the activity of the transcription", "activity of the transcription factor", "of the transcription factor tcf3", "transcription factor tcf3 e2a", "e2a through erk", "through erk dependent induction of", "erk dependent induction of id1.", "dependent induction of id1. inhibition", "induction of id1. inhibition of", "of id1. inhibition of tcf3", "id1. inhibition of tcf3 mediated", "inhibition of tcf3 mediated transcription", "of tcf3 mediated transcription downstream", "tcf3 mediated transcription downstream of", "mediated transcription downstream of notch3", "transcription downstream of notch3 contributes", "downstream of notch3 contributes to", "of notch3 contributes to development", "notch3 contributes to development of", "contributes to development of t", "to development of t cell", "development of t cell lymphomas", "of t cell lymphomas in", "t cell lymphomas in transgenic", "cell lymphomas in transgenic mice", "lymphomas in transgenic mice expressing", "in transgenic mice expressing nicd3", "mice expressing nicd3 talora", "expressing nicd3 talora et", "nicd3 talora et al.", "talora et al. 2003 .", "et al. 2003 . activation", "al. 2003 . activation of", "2003 . activation of erks", ". activation of erks downstream", "activation of erks downstream of", "of erks downstream of notch3", "erks downstream of notch3 stimulated", "downstream of notch3 stimulated pre", "of notch3 stimulated pre tcr", "notch3 stimulated pre tcr signaling", "stimulated pre tcr signaling leads", "pre tcr signaling leads to", "tcr signaling leads to phosphorylation", "signaling leads to phosphorylation of", "leads to phosphorylation of the", "to phosphorylation of the transcription", "phosphorylation of the transcription factor", "of the transcription factor tal1", "transcription factor tal1 formation", "factor tal1 formation of", "tal1 formation of the", "formation of the tal1:sp1 complex", "the tal1:sp1 complex and", "tal1:sp1 complex and activation", "complex and activation of", "and activation of cyclin d1", "of cyclin d1 ccnd1", "d1 ccnd1 transcription", "ccnd1 transcription which", "transcription which stimulates cell", "stimulates cell division talora", "cell division talora et", "division talora et al.", "talora et al. 2006 .

              notch3", "et al. 2006 .

              notch3 signaling", "al. 2006 .

              notch3 signaling can", "2006 .

              notch3 signaling can activate", ".

              notch3 signaling can activate nf", "signaling can activate nf kappab", "activate nf kappab nfkb", "kappab nfkb mediate", "nfkb mediate transcription either", "transcription either indirectly through", "either indirectly through activation", "indirectly through activation of", "through activation of pre tcr", "activation of pre tcr signaling", "pre tcr signaling or", "tcr signaling or directly", "or directly through association", "directly through association of", "through association of notch3 with", "association of notch3 with ikka.", "of notch3 with ikka. nfkb", "notch3 with ikka. nfkb is", "with ikka. nfkb is constitutively", "ikka. nfkb is constitutively active", "nfkb is constitutively active in", "is constitutively active in t", "constitutively active in t lymphoma", "active in t lymphoma cells", "in t lymphoma cells derived", "t lymphoma cells derived from", "lymphoma cells derived from notch3", "cells derived from notch3 transgenic", "derived from notch3 transgenic mice", "notch3 transgenic mice vacca", "transgenic mice vacca et", "mice vacca et al.", "vacca et al. 2006 .

              transcription", "et al. 2006 .

              transcription of", "al. 2006 .

              transcription of the", "2006 .

              transcription of the plxnd1", ".

              transcription of the plxnd1 gene", "the plxnd1 gene encoding", "plxnd1 gene encoding the", "gene encoding the semaphorin", "encoding the semaphorin receptor plexin", "the semaphorin receptor plexin d1", "receptor plexin d1 is", "plexin d1 is directly", "d1 is directly stimulated", "is directly stimulated by notch1", "directly stimulated by notch1 and", "stimulated by notch1 and notch3", "by notch1 and notch3 coactivator", "notch1 and notch3 coactivator complexes.", "and notch3 coactivator complexes. plxnd1", "notch3 coactivator complexes. plxnd1 is", "coactivator complexes. plxnd1 is involved", "complexes. plxnd1 is involved in", "plxnd1 is involved in neuronal", "is involved in neuronal migration", "involved in neuronal migration and", "in neuronal migration and cancer", "neuronal migration and cancer cell", "migration and cancer cell invasiveness", "cancer cell invasiveness rehman", "cell invasiveness rehman et", "invasiveness rehman et al.", "rehman et al. 2016 .", "et al. 2016 . expression", "al. 2016 . expression of", "2016 . expression of fabp7", "expression of fabp7 blbp", "fabp7 blbp in", "blbp in radial glia", "in radial glia is positively", "radial glia is positively regulated", "glia is positively regulated by", "is positively regulated by notch1", "positively regulated by notch1 and", "regulated by notch1 and notch3", "by notch1 and notch3 during", "notch1 and notch3 during neuronal", "and notch3 during neuronal migration", "during neuronal migration anthony", "neuronal migration anthony et", "migration anthony et al.", "et al. 2005 keilani", "al. 2005 keilani and", "2005 keilani and sugaya", "keilani and sugaya 2008 .


              notch3", "and sugaya 2008 .


              notch3 gene", "sugaya 2008 .


              notch3 gene is", "2008 .


              notch3 gene is frequently", ".


              notch3 gene is frequently amplified", "gene is frequently amplified in", "is frequently amplified in ovarian", "frequently amplified in ovarian cancer", "in ovarian cancer park", "ovarian cancer park et", "cancer park et al.", "park et al. 2006 .", "et al. 2006 . notch3", "al. 2006 . notch3 coactivator", "2006 . notch3 coactivator complex", ". notch3 coactivator complex directly", "notch3 coactivator complex directly stimulates", "coactivator complex directly stimulates dlgap5", "complex directly stimulates dlgap5 transcription.", "directly stimulates dlgap5 transcription. dlgap5", "stimulates dlgap5 transcription. dlgap5 is", "dlgap5 transcription. dlgap5 is involved", "transcription. dlgap5 is involved in", "dlgap5 is involved in g2/m", "is involved in g2/m transition", "involved in g2/m transition and", "in g2/m transition and is", "g2/m transition and is overexpressed", "transition and is overexpressed in", "and is overexpressed in ovarian", "is overexpressed in ovarian cancer", "overexpressed in ovarian cancer cells.", "ovarian cancer cells. chen", "cancer cells. chen et", "cells. chen et al.", "chen et al. 2012 .", "et al. 2012 . another", "al. 2012 . another gene", "2012 . another gene overexpressed", ". another gene overexpressed in", "another gene overexpressed in ovarian", "gene overexpressed in ovarian cancer", "overexpressed in ovarian cancer whose", "in ovarian cancer whose transcription", "ovarian cancer whose transcription is", "cancer whose transcription is directly", "whose transcription is directly stimulated", "transcription is directly stimulated by", "is directly stimulated by notch3", "directly stimulated by notch3 is", "stimulated by notch3 is pbx1", "notch3 is pbx1 park", "is pbx1 park et", "pbx1 park et al.", "park et al. 2008 .", "et al. 2008 . the", "al. 2008 . the notch3", "2008 . the notch3 coactivator", ". the notch3 coactivator complex", "the notch3 coactivator complex directly", "coactivator complex directly stimulates wwc1", "complex directly stimulates wwc1 gene", "directly stimulates wwc1 gene transcription.", "stimulates wwc1 gene transcription. wwc1", "wwc1 gene transcription. wwc1 gene", "gene transcription. wwc1 gene encodes", "transcription. wwc1 gene encodes protein", "wwc1 gene encodes protein kibra", "encodes protein kibra involved", "protein kibra involved in", "kibra involved in hippo", "involved in hippo signaling. notch3", "in hippo signaling. notch3 mediated", "hippo signaling. notch3 mediated induction", "signaling. notch3 mediated induction of", "notch3 mediated induction of wwc1", "induction of wwc1 positively", "of wwc1 positively regulates", "wwc1 positively regulates hippo", "positively regulates hippo signaling and", "regulates hippo signaling and inhibits", "hippo signaling and inhibits epithelial", "signaling and inhibits epithelial to", "and inhibits epithelial to mesenchymal", "inhibits epithelial to mesenchymal transition", "to mesenchymal transition emt", "transition emt in", "emt in triple negative", "in triple negative breast cancer", "triple negative breast cancer cells", "breast cancer cells zhang", "cancer cells zhang et", "cells zhang et al.", "zhang et al. 2016 .
              " ] }, { "record_id": "GLY_000594_1_1190", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9014843", "r hsa", "hsa 9014843", "r hsa 9014843" ] }, { "record_id": "GLY_000594_1_1190", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 33", "33 signaling", "interleukin 33 signaling", "cytokine is", "is a", "a member", "member of", "of the", "the interleukin", "interleukin 1", "1 family.", "family. it", "it can", "can be", "be classified", "classified as", "as an", "an alarmin", "alarmin because", "because it", "it is", "is released", "released into", "into the", "the extracellular", "extracellular space", "space during", "during cell", "cell damage.", "damage. it", "it acts", "acts as", "an endogenous", "endogenous danger", "danger signal", "liew et", "et al.", "al. 2010", "2010 .", "the gene", "gene product", "product is", "is biologically", "biologically active", "full length", "length il33", "il33 .", ". its", "its potency", "potency has", "has been", "been reported", "reported to", "to increase", "increase significantly", "up to", "to 30x", "after cleavage", "cleavage at", "at the", "the n", "n terminus", "terminus by", "by inflammatory", "inflammatory proteases", "proteases such", "such as", "as cathepsin", "cathepsin g", "and neutrophil", "neutrophil elastase", "lefran\u00e7ais et", "al. 2012", "al. 2014", "but others", "others have", "have suggested", "suggested that", "that processing", "processing inactivates", "inactivates il33", "cayrol &", "& girard", "girard 2009", "2009 .", ". il33", "il33 can", "can act", "act as", "an extracellular", "extracellular ligand", "ligand and", "and an", "an intracellular", "intracellular signaling", "signaling molecule", "martin et", "al. 2013", "2016 .", ". full", "il33 has", "has a", "a nuclear", "nuclear localization", "localization sequence", "sequence and", "and can", "can translocate", "translocate to", "to the", "the nucleus", "where it", "it binds", "binds heterochromatin", "moussion et", "al. 2008", "carriere et", "al. 2007", "roussel et", "kuchler et", "sundlisaeter et", "baekkevold et", "al. 2003", "2003 .", "il33 that", "that has", "has undergone", "undergone proteolytic", "proteolytic processing", "processing is", "is unable", "unable to", "to translocate", "ali et", ". binding", "binding of", "of extracellular", "extracellular il33", "il33 to", "to its", "its receptor", "receptor interleukin", "1 receptor", "receptor like", "like 1", "suppression of", "of tumorigenicity", "tumorigenicity 2", "initiates several", "several cellular", "cellular signaling", "signaling pathways.", "pathways. cell", "cell injury", "injury or", "or death", "death are", "are the", "the dominant", "dominant mechanisms", "mechanisms by", "by which", "which il33", "il33 reaches", "reaches the", "extracellular environment", "il33 is", "is not", "not actively", "actively secreted", "secreted by", "by cells", "al. 2016", "kaczmarek et", "vancamelbeke et", "al. 2017", "2017 .", ". because", "because il33", "is expressed", "expressed constitutively", "constitutively by", "by endothelial", "endothelial and", "and epithelial", "epithelial cells", "cells it", "is immediately", "immediately available", "available to", "extracellular microenvironment", "microenvironment after", "after cell", "injury and", "and necrosis", "2012 .", ". increases", "increases in", "in extracellular", "extracellular atp", "atp or", "or mechanical", "mechanical stress", "stress correlate", "correlate with", "with increased", "increased il33", "il33 secretion", "secretion by", "by mast", "mast cells", "cells or", "or cardiomyocytes", "shimokawa et", "kakkar et", "zhao et", "sanada et", "chen et", "al. 2015", "2015 .", ". soluble", "soluble il1rl1", "il1rl1 isoform", "isoform c", "iwahana et", "al. 2005", "tominaga et", "al. 1999", "shares the", "extracellular components", "components of", "of il1rl1", "including the", "the ligand", "ligand binding", "binding domain", "but lacks", "lacks the", "the transmembrane", "transmembrane and", "and intracellular", "intracellular components", "1999 .", ". the", "the il33", "il33 il1rl1", "il1rl1 complex", "complex recruits", "recruits a", "a co", "co receptor", "most commonly", "commonly il1", "il1 receptor", "receptor accessory", "accessory protein", "il 1racp", "schmitz et", "lingel et", "al. 2009", "palmer et", "liu et", "2013 .", "33 il33", "il33 cytokine", "cytokine is a", "is a member", "a member of", "member of the", "of the interleukin", "the interleukin 1", "interleukin 1 family.", "1 family. it", "family. it can", "it can be", "can be classified", "be classified as", "classified as an", "as an alarmin", "an alarmin because", "alarmin because it", "because it is", "it is released", "is released into", "released into the", "into the extracellular", "the extracellular space", "extracellular space during", "space during cell", "during cell damage.", "cell damage. it", "damage. it acts", "it acts as", "acts as an", "as an endogenous", "an endogenous danger", "endogenous danger signal", "signal liew", "liew et al.", "et al. 2010", "al. 2010 .", "the gene product", "gene product is", "product is biologically", "is biologically active", "active full", "full length il33", "length il33 .", "il33 . its", ". its potency", "its potency has", "potency has been", "has been reported", "been reported to", "reported to increase", "to increase significantly", "significantly up", "up to 30x", "30x after", "after cleavage at", "cleavage at the", "at the n", "the n terminus", "n terminus by", "terminus by inflammatory", "by inflammatory proteases", "inflammatory proteases such", "proteases such as", "such as cathepsin", "as cathepsin g", "g ctsg", "ctsg and", "and neutrophil elastase", "elastase elane", "lefran\u00e7ais et al.", "et al. 2012", "2012 lefran\u00e7ais", "et al. 2014", "2014 but", "but others have", "others have suggested", "have suggested that", "suggested that processing", "that processing inactivates", "processing inactivates il33", "il33 cayrol", "cayrol & girard", "& girard 2009", "girard 2009 .", "2009 . il33", ". il33 can", "il33 can act", "can act as", "act as an", "as an extracellular", "an extracellular ligand", "extracellular ligand and", "ligand and an", "and an intracellular", "an intracellular signaling", "intracellular signaling molecule", "molecule martin", "martin et al.", "et al. 2013", "2013 2016", "2016 . full", ". full length", "length il33 has", "il33 has a", "has a nuclear", "a nuclear localization", "nuclear localization sequence", "localization sequence and", "sequence and can", "and can translocate", "can translocate to", "translocate to the", "to the nucleus", "nucleus where", "where it binds", "it binds heterochromatin", "heterochromatin moussion", "moussion et al.", "et al. 2008", "2008 carriere", "carriere et al.", "et al. 2007", "2007 roussel", "roussel et al.", "2008 kuchler", "kuchler et al.", "2008 sundlisaeter", "sundlisaeter et al.", "2012 baekkevold", "baekkevold et al.", "et al. 2003", "al. 2003 .", "2003 . il33", ". il33 that", "il33 that has", "that has undergone", "has undergone proteolytic", "undergone proteolytic processing", "proteolytic processing is", "processing is unable", "is unable to", "unable to translocate", "to translocate to", "nucleus martin", "2013 ali", "ali et al.", "2010 . binding", ". binding of", "binding of extracellular", "of extracellular il33", "extracellular il33 to", "il33 to its", "to its receptor", "its receptor interleukin", "receptor interleukin 1", "interleukin 1 receptor", "1 receptor like", "receptor like 1", "1 il1rl1", "il1rl1 suppression", "suppression of tumorigenicity", "of tumorigenicity 2", "2 st2", "st2 initiates", "initiates several cellular", "several cellular signaling", "cellular signaling pathways.", "signaling pathways. cell", "pathways. cell injury", "cell injury or", "injury or death", "or death are", "death are the", "are the dominant", "the dominant mechanisms", "dominant mechanisms by", "mechanisms by which", "by which il33", "which il33 reaches", "il33 reaches the", "reaches the extracellular", "the extracellular environment", "environment il33", "il33 is not", "is not actively", "not actively secreted", "actively secreted by", "secreted by cells", "cells martin", "et al. 2016", "2016 kaczmarek", "kaczmarek et al.", "2013 vancamelbeke", "vancamelbeke et al.", "et al. 2017", "al. 2017 .", "2017 . because", ". because il33", "because il33 is", "il33 is expressed", "is expressed constitutively", "expressed constitutively by", "constitutively by endothelial", "by endothelial and", "endothelial and epithelial", "and epithelial cells", "epithelial cells it", "cells it is", "it is immediately", "is immediately available", "immediately available to", "available to the", "to the extracellular", "the extracellular microenvironment", "extracellular microenvironment after", "microenvironment after cell", "after cell injury", "cell injury and", "injury and necrosis", "necrosis lefran\u00e7ais", "al. 2012 .", "2012 . increases", ". increases in", "increases in extracellular", "in extracellular atp", "extracellular atp or", "atp or mechanical", "or mechanical stress", "mechanical stress correlate", "stress correlate with", "correlate with increased", "with increased il33", "increased il33 secretion", "il33 secretion by", "secretion by mast", "by mast cells", "mast cells or", "cells or cardiomyocytes", "cardiomyocytes respectively", "respectively shimokawa", "shimokawa et al.", "2017 kakkar", "kakkar et al.", "2012 zhao", "zhao et al.", "2012 sanada", "sanada et al.", "2007 chen", "chen et al.", "et al. 2015", "al. 2015 .", "2015 . soluble", ". soluble il1rl1", "il1rl1 il1rl1", "il1rl1 isoform c", "c st2v", "iwahana et al.", "et al. 2005", "2005 tominaga", "tominaga et al.", "et al. 1999", "1999 shares", "shares the extracellular", "the extracellular components", "extracellular components of", "components of il1rl1", "il1rl1 including", "including the ligand", "the ligand binding", "ligand binding domain", "domain but", "but lacks the", "lacks the transmembrane", "the transmembrane and", "transmembrane and intracellular", "and intracellular components", "intracellular components of", "il1rl1 kakkar", "2008 iwahana", "al. 1999 .", "1999 . the", ". the il33", "the il33 il1rl1", "il33 il1rl1 complex", "il1rl1 complex recruits", "complex recruits a", "recruits a co", "a co receptor", "receptor most", "most commonly il1", "commonly il1 receptor", "il1 receptor accessory", "receptor accessory protein", "protein il1rap", "il1rap il", "schmitz et al.", "2005 lingel", "lingel et al.", "et al. 2009", "2009 palmer", "palmer et al.", "2008 liu", "liu et al.", "al. 2013 .", "interleukin 33 il33", "il33 cytokine is", "cytokine is a member", "is a member of", "a member of the", "member of the interleukin", "of the interleukin 1", "the interleukin 1 family.", "interleukin 1 family. it", "1 family. it can", "family. it can be", "it can be classified", "can be classified as", "be classified as an", "classified as an alarmin", "as an alarmin because", "an alarmin because it", "alarmin because it is", "because it is released", "it is released into", "is released into the", "released into the extracellular", "into the extracellular space", "the extracellular space during", "extracellular space during cell", "space during cell damage.", "during cell damage. it", "cell damage. it acts", "damage. it acts as", "it acts as an", "acts as an endogenous", "as an endogenous danger", "an endogenous danger signal", "danger signal liew", "signal liew et", "liew et al. 2010", "et al. 2010 .", "2010 . the", ". the gene", "the gene product is", "gene product is biologically", "product is biologically active", "biologically active full", "active full length", "full length il33 .", "length il33 . its", "il33 . its potency", ". its potency has", "its potency has been", "potency has been reported", "has been reported to", "been reported to increase", "reported to increase significantly", "increase significantly up", "significantly up to", "to 30x after", "30x after cleavage", "after cleavage at the", "cleavage at the n", "at the n terminus", "the n terminus by", "n terminus by inflammatory", "terminus by inflammatory proteases", "by inflammatory proteases such", "inflammatory proteases such as", "proteases such as cathepsin", "such as cathepsin g", "cathepsin g ctsg", "ctsg and neutrophil", "neutrophil elastase elane", "elane lefran\u00e7ais", "lefran\u00e7ais et al. 2012", "al. 2012 lefran\u00e7ais", "2012 lefran\u00e7ais et", "lefran\u00e7ais et al. 2014", "al. 2014 but", "2014 but others", "but others have suggested", "others have suggested that", "have suggested that processing", "suggested that processing inactivates", "that processing inactivates il33", "inactivates il33 cayrol", "il33 cayrol &", "cayrol & girard 2009", "& girard 2009 .", "girard 2009 . il33", "2009 . il33 can", ". il33 can act", "il33 can act as", "can act as an", "act as an extracellular", "as an extracellular ligand", "an extracellular ligand and", "extracellular ligand and an", "ligand and an intracellular", "and an intracellular signaling", "an intracellular signaling molecule", "signaling molecule martin", "molecule martin et", "martin et al. 2013", "al. 2013 2016", "2013 2016 .", "2016 . full length", ". full length il33", "full length il33 has", "length il33 has a", "il33 has a nuclear", "has a nuclear localization", "a nuclear localization sequence", "nuclear localization sequence and", "localization sequence and can", "sequence and can translocate", "and can translocate to", "can translocate to the", "translocate to the nucleus", "the nucleus where", "nucleus where it", "where it binds heterochromatin", "binds heterochromatin moussion", "heterochromatin moussion et", "moussion et al. 2008", "al. 2008 carriere", "2008 carriere et", "carriere et al. 2007", "al. 2007 roussel", "2007 roussel et", "roussel et al. 2008", "al. 2008 kuchler", "2008 kuchler et", "kuchler et al. 2008", "al. 2008 sundlisaeter", "2008 sundlisaeter et", "sundlisaeter et al. 2012", "al. 2012 baekkevold", "2012 baekkevold et", "baekkevold et al. 2003", "et al. 2003 .", "al. 2003 . il33", "2003 . il33 that", ". il33 that has", "il33 that has undergone", "that has undergone proteolytic", "has undergone proteolytic processing", "undergone proteolytic processing is", "proteolytic processing is unable", "processing is unable to", "is unable to translocate", "unable to translocate to", "to translocate to the", "the nucleus martin", "nucleus martin et", "al. 2013 ali", "2013 ali et", "ali et al. 2010", "al. 2010 . binding", "2010 . binding of", ". binding of extracellular", "binding of extracellular il33", "of extracellular il33 to", "extracellular il33 to its", "il33 to its receptor", "to its receptor interleukin", "its receptor interleukin 1", "receptor interleukin 1 receptor", "interleukin 1 receptor like", "1 receptor like 1", "like 1 il1rl1", "il1rl1 suppression of", "suppression of tumorigenicity 2", "tumorigenicity 2 st2", "st2 initiates several", "initiates several cellular signaling", "several cellular signaling pathways.", "cellular signaling pathways. cell", "signaling pathways. cell injury", "pathways. cell injury or", "cell injury or death", "injury or death are", "or death are the", "death are the dominant", "are the dominant mechanisms", "the dominant mechanisms by", "dominant mechanisms by which", "mechanisms by which il33", "by which il33 reaches", "which il33 reaches the", "il33 reaches the extracellular", "reaches the extracellular environment", "extracellular environment il33", "environment il33 is", "il33 is not actively", "is not actively secreted", "not actively secreted by", "actively secreted by cells", "by cells martin", "cells martin et", "martin et al. 2016", "al. 2016 kaczmarek", "2016 kaczmarek et", "kaczmarek et al. 2013", "al. 2013 vancamelbeke", "2013 vancamelbeke et", "vancamelbeke et al. 2017", "et al. 2017 .", "al. 2017 . because", "2017 . because il33", ". because il33 is", "because il33 is expressed", "il33 is expressed constitutively", "is expressed constitutively by", "expressed constitutively by endothelial", "constitutively by endothelial and", "by endothelial and epithelial", "endothelial and epithelial cells", "and epithelial cells it", "epithelial cells it is", "cells it is immediately", "it is immediately available", "is immediately available to", "immediately available to the", "available to the extracellular", "to the extracellular microenvironment", "the extracellular microenvironment after", "extracellular microenvironment after cell", "microenvironment after cell injury", "after cell injury and", "cell injury and necrosis", "and necrosis lefran\u00e7ais", "necrosis lefran\u00e7ais et", "et al. 2012 .", "al. 2012 . increases", "2012 . increases in", ". increases in extracellular", "increases in extracellular atp", "in extracellular atp or", "extracellular atp or mechanical", "atp or mechanical stress", "or mechanical stress correlate", "mechanical stress correlate with", "stress correlate with increased", "correlate with increased il33", "with increased il33 secretion", "increased il33 secretion by", "il33 secretion by mast", "secretion by mast cells", "by mast cells or", "mast cells or cardiomyocytes", "or cardiomyocytes respectively", "respectively shimokawa et", "shimokawa et al. 2017", "al. 2017 kakkar", "2017 kakkar et", "kakkar et al. 2012", "al. 2012 zhao", "2012 zhao et", "zhao et al. 2012", "al. 2012 sanada", "2012 sanada et", "sanada et al. 2007", "al. 2007 chen", "2007 chen et", "chen et al. 2015", "et al. 2015 .", "al. 2015 . soluble", "2015 . soluble il1rl1", "soluble il1rl1 il1rl1", "il1rl1 il1rl1 isoform", "isoform c st2v", "st2v iwahana", "iwahana et al. 2005", "al. 2005 tominaga", "2005 tominaga et", "tominaga et al. 1999", "al. 1999 shares", "1999 shares the", "shares the extracellular components", "the extracellular components of", "extracellular components of il1rl1", "of il1rl1 including", "il1rl1 including the", "including the ligand binding", "the ligand binding domain", "binding domain but", "domain but lacks", "but lacks the transmembrane", "lacks the transmembrane and", "the transmembrane and intracellular", "transmembrane and intracellular components", "and intracellular components of", "intracellular components of il1rl1", "of il1rl1 kakkar", "il1rl1 kakkar et", "kakkar et al. 2008", "al. 2008 iwahana", "2008 iwahana et", "iwahana et al. 1999", "et al. 1999 .", "al. 1999 . the", "1999 . the il33", ". the il33 il1rl1", "the il33 il1rl1 complex", "il33 il1rl1 complex recruits", "il1rl1 complex recruits a", "complex recruits a co", "recruits a co receptor", "co receptor most", "receptor most commonly", "most commonly il1 receptor", "commonly il1 receptor accessory", "il1 receptor accessory protein", "accessory protein il1rap", "il1rap il 1racp", "1racp schmitz", "schmitz et al. 2005", "al. 2005 lingel", "2005 lingel et", "lingel et al. 2009", "al. 2009 palmer", "2009 palmer et", "palmer et al. 2008", "al. 2008 liu", "2008 liu et", "liu et al. 2013", "et al. 2013 .", "33 il33 cytokine", "il33 cytokine is a", "cytokine is a member of", "is a member of the", "a member of the interleukin", "member of the interleukin 1", "of the interleukin 1 family.", "the interleukin 1 family. it", "interleukin 1 family. it can", "1 family. it can be", "family. it can be classified", "it can be classified as", "can be classified as an", "be classified as an alarmin", "classified as an alarmin because", "as an alarmin because it", "an alarmin because it is", "alarmin because it is released", "because it is released into", "it is released into the", "is released into the extracellular", "released into the extracellular space", "into the extracellular space during", "the extracellular space during cell", "extracellular space during cell damage.", "space during cell damage. it", "during cell damage. it acts", "cell damage. it acts as", "damage. it acts as an", "it acts as an endogenous", "acts as an endogenous danger", "as an endogenous danger signal", "endogenous danger signal liew", "danger signal liew et", "signal liew et al.", "liew et al. 2010 .", "al. 2010 . the", "2010 . the gene", ". the gene product", "the gene product is biologically", "gene product is biologically active", "is biologically active full", "biologically active full length", "active full length il33", "full length il33 . its", "length il33 . its potency", "il33 . its potency has", ". its potency has been", "its potency has been reported", "potency has been reported to", "has been reported to increase", "been reported to increase significantly", "to increase significantly up", "increase significantly up to", "significantly up to 30x", "up to 30x after", "to 30x after cleavage", "30x after cleavage at", "after cleavage at the n", "cleavage at the n terminus", "at the n terminus by", "the n terminus by inflammatory", "n terminus by inflammatory proteases", "terminus by inflammatory proteases such", "by inflammatory proteases such as", "inflammatory proteases such as cathepsin", "proteases such as cathepsin g", "as cathepsin g ctsg", "g ctsg and", "ctsg and neutrophil elastase", "and neutrophil elastase elane", "elane lefran\u00e7ais et", "et al. 2012 lefran\u00e7ais", "al. 2012 lefran\u00e7ais et", "2012 lefran\u00e7ais et al.", "et al. 2014 but", "al. 2014 but others", "2014 but others have", "but others have suggested that", "others have suggested that processing", "have suggested that processing inactivates", "suggested that processing inactivates il33", "processing inactivates il33 cayrol", "inactivates il33 cayrol &", "il33 cayrol & girard", "cayrol & girard 2009 .", "& girard 2009 . il33", "girard 2009 . il33 can", "2009 . il33 can act", ". il33 can act as", "il33 can act as an", "can act as an extracellular", "act as an extracellular ligand", "as an extracellular ligand and", "an extracellular ligand and an", "extracellular ligand and an intracellular", "ligand and an intracellular signaling", "and an intracellular signaling molecule", "intracellular signaling molecule martin", "signaling molecule martin et", "molecule martin et al.", "et al. 2013 2016", "al. 2013 2016 .", "2013 2016 . full", "2016 . full length il33", ". full length il33 has", "full length il33 has a", "length il33 has a nuclear", "il33 has a nuclear localization", "has a nuclear localization sequence", "a nuclear localization sequence and", "nuclear localization sequence and can", "localization sequence and can translocate", "sequence and can translocate to", "and can translocate to the", "can translocate to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it binds", "it binds heterochromatin moussion", "binds heterochromatin moussion et", "heterochromatin moussion et al.", "et al. 2008 carriere", "al. 2008 carriere et", "2008 carriere et al.", "et al. 2007 roussel", "al. 2007 roussel et", "2007 roussel et al.", "et al. 2008 kuchler", "al. 2008 kuchler et", "2008 kuchler et al.", "et al. 2008 sundlisaeter", "al. 2008 sundlisaeter et", "2008 sundlisaeter et al.", "et al. 2012 baekkevold", "al. 2012 baekkevold et", "2012 baekkevold et al.", "baekkevold et al. 2003 .", "et al. 2003 . il33", "al. 2003 . il33 that", "2003 . il33 that has", ". il33 that has undergone", "il33 that has undergone proteolytic", "that has undergone proteolytic processing", "has undergone proteolytic processing is", "undergone proteolytic processing is unable", "proteolytic processing is unable to", "processing is unable to translocate", "is unable to translocate to", "unable to translocate to the", "to translocate to the nucleus", "to the nucleus martin", "the nucleus martin et", "nucleus martin et al.", "et al. 2013 ali", "al. 2013 ali et", "2013 ali et al.", "ali et al. 2010 .", "et al. 2010 . binding", "al. 2010 . binding of", "2010 . binding of extracellular", ". binding of extracellular il33", "binding of extracellular il33 to", "of extracellular il33 to its", "extracellular il33 to its receptor", "il33 to its receptor interleukin", "to its receptor interleukin 1", "its receptor interleukin 1 receptor", "receptor interleukin 1 receptor like", "interleukin 1 receptor like 1", "receptor like 1 il1rl1", "1 il1rl1 suppression", "il1rl1 suppression of tumorigenicity", "of tumorigenicity 2 st2", "2 st2 initiates", "st2 initiates several cellular", "initiates several cellular signaling pathways.", "several cellular signaling pathways. cell", "cellular signaling pathways. cell injury", "signaling pathways. cell injury or", "pathways. cell injury or death", "cell injury or death are", "injury or death are the", "or death are the dominant", "death are the dominant mechanisms", "are the dominant mechanisms by", "the dominant mechanisms by which", "dominant mechanisms by which il33", "mechanisms by which il33 reaches", "by which il33 reaches the", "which il33 reaches the extracellular", "il33 reaches the extracellular environment", "the extracellular environment il33", "extracellular environment il33 is", "environment il33 is not", "il33 is not actively secreted", "is not actively secreted by", "not actively secreted by cells", "secreted by cells martin", "by cells martin et", "cells martin et al.", "et al. 2016 kaczmarek", "al. 2016 kaczmarek et", "2016 kaczmarek et al.", "et al. 2013 vancamelbeke", "al. 2013 vancamelbeke et", "2013 vancamelbeke et al.", "vancamelbeke et al. 2017 .", "et al. 2017 . because", "al. 2017 . because il33", "2017 . because il33 is", ". because il33 is expressed", "because il33 is expressed constitutively", "il33 is expressed constitutively by", "is expressed constitutively by endothelial", "expressed constitutively by endothelial and", "constitutively by endothelial and epithelial", "by endothelial and epithelial cells", "endothelial and epithelial cells it", "and epithelial cells it is", "epithelial cells it is immediately", "cells it is immediately available", "it is immediately available to", "is immediately available to the", "immediately available to the extracellular", "available to the extracellular microenvironment", "to the extracellular microenvironment after", "the extracellular microenvironment after cell", "extracellular microenvironment after cell injury", "microenvironment after cell injury and", "after cell injury and necrosis", "injury and necrosis lefran\u00e7ais", "and necrosis lefran\u00e7ais et", "necrosis lefran\u00e7ais et al.", "lefran\u00e7ais et al. 2012 .", "et al. 2012 . increases", "al. 2012 . increases in", "2012 . increases in extracellular", ". increases in extracellular atp", "increases in extracellular atp or", "in extracellular atp or mechanical", "extracellular atp or mechanical stress", "atp or mechanical stress correlate", "or mechanical stress correlate with", "mechanical stress correlate with increased", "stress correlate with increased il33", "correlate with increased il33 secretion", "with increased il33 secretion by", "increased il33 secretion by mast", "il33 secretion by mast cells", "secretion by mast cells or", "by mast cells or cardiomyocytes", "cells or cardiomyocytes respectively", "cardiomyocytes respectively shimokawa", "respectively shimokawa et al.", "et al. 2017 kakkar", "al. 2017 kakkar et", "2017 kakkar et al.", "et al. 2012 zhao", "al. 2012 zhao et", "2012 zhao et al.", "et al. 2012 sanada", "al. 2012 sanada et", "2012 sanada et al.", "et al. 2007 chen", "al. 2007 chen et", "2007 chen et al.", "chen et al. 2015 .", "et al. 2015 . soluble", "al. 2015 . soluble il1rl1", ". soluble il1rl1 il1rl1", "soluble il1rl1 il1rl1 isoform", "il1rl1 il1rl1 isoform c", "il1rl1 isoform c st2v", "st2v iwahana et", "et al. 2005 tominaga", "al. 2005 tominaga et", "2005 tominaga et al.", "et al. 1999 shares", "al. 1999 shares the", "1999 shares the extracellular", "shares the extracellular components of", "the extracellular components of il1rl1", "components of il1rl1 including", "of il1rl1 including the", "il1rl1 including the ligand", "including the ligand binding domain", "ligand binding domain but", "binding domain but lacks", "domain but lacks the", "but lacks the transmembrane and", "lacks the transmembrane and intracellular", "the transmembrane and intracellular components", "transmembrane and intracellular components of", "and intracellular components of il1rl1", "components of il1rl1 kakkar", "of il1rl1 kakkar et", "il1rl1 kakkar et al.", "et al. 2008 iwahana", "al. 2008 iwahana et", "2008 iwahana et al.", "iwahana et al. 1999 .", "et al. 1999 . the", "al. 1999 . the il33", "1999 . the il33 il1rl1", ". the il33 il1rl1 complex", "the il33 il1rl1 complex recruits", "il33 il1rl1 complex recruits a", "il1rl1 complex recruits a co", "complex recruits a co receptor", "a co receptor most", "co receptor most commonly", "receptor most commonly il1", "most commonly il1 receptor accessory", "commonly il1 receptor accessory protein", "receptor accessory protein il1rap", "protein il1rap il", "il 1racp schmitz", "1racp schmitz et", "et al. 2005 lingel", "al. 2005 lingel et", "2005 lingel et al.", "et al. 2009 palmer", "al. 2009 palmer et", "2009 palmer et al.", "et al. 2008 liu", "al. 2008 liu et", "2008 liu et al.", "liu et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1191", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020558", "r hsa", "hsa 9020558", "r hsa 9020558" ] }, { "record_id": "GLY_000594_1_1191", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 2", "2 signaling", "interleukin 2 signaling", "il 2", "is a", "a cytokine", "cytokine that", "that is", "is produced", "produced by", "by t", "t cells", "cells in", "in response", "response to", "to antigen", "antigen stimulation.", "stimulation. originally", "2 was", "was discovered", "discovered because", "because of", "of its", "its potent", "potent growth", "growth factor", "factor activity", "activity on", "on activated", "activated t", "in vitro", "vitro and", "and was", "was therefore", "therefore named", "named 't", "'t cell", "cell growth", "growth factor'", "tcgf .", ". however", "the generation", "generation of", "of il", "and il", "2 receptor", "receptor deficient", "deficient mice", "mice revealed", "revealed that", "that il", "2 also", "also plays", "plays a", "a regulatory", "regulatory role", "role in", "in the", "the immune", "immune system", "system by", "by suppressing", "suppressing autoimmune", "autoimmune responses.", "responses. two", "two main", "main mechanisms", "mechanisms have", "have been", "been identified", "identified that", "that explain", "explain this", "this suppressive", "suppressive function:", "2 sensitizes", "sensitizes activated", "cells for", "for activation", "activation induced", "induced cell", "cell death", "2 is", "is critical", "critical for", "for the", "the survival", "survival and", "and function", "function of", "of regulatory", "regulatory t", "which possess", "possess potent", "potent immunosuppressive", "immunosuppressive properties.

              il", "properties.

              il 2", "signaling occurs", "occurs when", "when il", "2 binds", "binds to", "to the", "the heterotrimeric", "heterotrimeric high", "high affinity", "affinity il", "il 2r", "which consists", "consists of", "of alpha", "beta and", "and gamma", "gamma chains.", "chains. the", "the il", "2r was", "was identified", "identified in", "in 1981", "1981 via", "via radiolabeled", "radiolabeled ligand", "ligand binding", "robb et", "et al.", "al. 1981", "1981 .", ". the", "2r alpha", "alpha chain", "chain was", "in 1982", "leonard et", "the beta", "beta chain", "chain in", "in 1986/7", "sharon et", "al. 1986", "teshigawara et", "al. 1987", "and the", "2r gamma", "gamma chain", "in 1992", "takeshita et", "al. .", "the high", "affinity of", "2 binding", "binding to", "2r is", "is created", "created by", "by a", "a very", "very rapid", "rapid association", "association rate", "rate to", "combined with", "with a", "a much", "much slower", "slower dissociation", "dissociation rate", "rate contributed", "contributed by", "by the", "the combination", "combination of", "of the", "2r beta", "gamma chains", "wang &", "& smith", "smith 1987", "1987 .", ". after", "after antigen", "antigen stimulation", "cells upregulate", "upregulate the", "alpha captures", "captures il", "2 and", "and this", "this complex", "complex then", "then associates", "associates with", "with the", "the constitutively", "constitutively expressed", "expressed il", "chain is", "is shared", "shared by", "by several", "several other", "other members", "members of", "the cytokine", "cytokine receptor", "receptor superfamily", "superfamily including", "including il", "il 4", "il 7", "il 9", "il 15", "15 and", "il 21", "21 receptors", "and consequently", "consequently is", "is often", "often referred", "referred to", "to as", "as the", "the common", "common gamma", "gamma c", "c .", "the tyrosine", "tyrosine kinases", "kinases jak1", "jak1 and", "and jak3", "which are", "are constitutively", "constitutively associated", "associated with", "with il", "c respectively", "are activated", "activated resulting", "resulting in", "in phosphorylation", "phosphorylation of", "of three", "three critical", "critical tyrosine", "tyrosine residues", "residues in", "beta cytoplasmic", "cytoplasmic tail.", "tail. these", "these phosphorylated", "phosphorylated residues", "residues enable", "enable recruitment", "recruitment of", "the adaptor", "adaptor molecule", "molecule shc", "activating the", "the mapk", "mapk and", "and pi3k", "pi3k pathways", "the transcription", "transcription factor", "factor stat5.", "stat5. after", "after phosphorylation", "stat5 forms", "forms dimers", "dimers that", "that translocate", "translocate to", "the nucleus", "nucleus and", "and initiate", "initiate gene", "gene expression.", "expression. while", "while stat5", "stat5 activation", "activation is", "for il", "2 function", "function in", "in most", "most cell", "cell types", "the contribution", "contribution of", "the pi3k/akt", "pi3k/akt pathway", "pathway differs", "differs between", "between distinct", "distinct t", "t cell", "cell subsets.", "subsets. in", "in tregs", "tregs for", "for example", "pi3k/akt is", "is not", "not involved", "involved in", "in il", "signaling and", "this may", "may explain", "explain some", "some of", "the different", "different functional", "functional outcomes", "outcomes of", "signaling in", "tregs vs.", "vs. effector", "effector t", "t cells.", "2 il", "is a cytokine", "a cytokine that", "cytokine that is", "that is produced", "is produced by", "produced by t", "by t cells", "t cells in", "cells in response", "in response to", "response to antigen", "to antigen stimulation.", "antigen stimulation. originally", "originally il", "il 2 was", "2 was discovered", "was discovered because", "discovered because of", "because of its", "of its potent", "its potent growth", "potent growth factor", "growth factor activity", "factor activity on", "activity on activated", "on activated t", "activated t cells", "cells in vitro", "in vitro and", "vitro and was", "and was therefore", "was therefore named", "therefore named 't", "named 't cell", "'t cell growth", "cell growth factor'", "factor' tcgf", "tcgf . however", "however the", "the generation of", "generation of il", "of il 2", "and il 2", "il 2 receptor", "2 receptor deficient", "receptor deficient mice", "deficient mice revealed", "mice revealed that", "revealed that il", "that il 2", "il 2 also", "2 also plays", "also plays a", "plays a regulatory", "a regulatory role", "regulatory role in", "role in the", "in the immune", "the immune system", "immune system by", "system by suppressing", "by suppressing autoimmune", "suppressing autoimmune responses.", "autoimmune responses. two", "responses. two main", "two main mechanisms", "main mechanisms have", "mechanisms have been", "have been identified", "been identified that", "identified that explain", "that explain this", "explain this suppressive", "this suppressive function:", "function: 1", "1 il", "il 2 sensitizes", "2 sensitizes activated", "sensitizes activated t", "t cells for", "cells for activation", "for activation induced", "activation induced cell", "induced cell death", "death aicd", "aicd and", "and 2", "il 2 is", "2 is critical", "is critical for", "critical for the", "for the survival", "the survival and", "survival and function", "and function of", "function of regulatory", "of regulatory t", "regulatory t cells", "cells tregs", "which possess potent", "possess potent immunosuppressive", "potent immunosuppressive properties.

              il", "immunosuppressive properties.

              il 2", "properties.

              il 2 signaling", "2 signaling occurs", "signaling occurs when", "occurs when il", "when il 2", "il 2 binds", "2 binds to", "binds to the", "to the heterotrimeric", "the heterotrimeric high", "heterotrimeric high affinity", "high affinity il", "affinity il 2", "receptor il", "which consists of", "consists of alpha", "alpha beta", "beta and gamma", "and gamma chains.", "gamma chains. the", "chains. the il", "the il 2r", "il 2r was", "2r was identified", "was identified in", "identified in 1981", "in 1981 via", "1981 via radiolabeled", "via radiolabeled ligand", "radiolabeled ligand binding", "binding robb", "robb et al.", "et al. 1981", "al. 1981 .", "1981 . the", ". the il", "il 2r alpha", "2r alpha chain", "alpha chain was", "identified in 1982", "1982 leonard", "leonard et al.", "the beta chain", "beta chain in", "chain in 1986/7", "1986/7 sharon", "sharon et al.", "et al. 1986", "1986 teshigawara", "teshigawara et al.", "et al. 1987", "1987 and", "and the il", "il 2r gamma", "2r gamma chain", "gamma chain in", "chain in 1992", "1992 takeshita", "takeshita et al.", "et al. .", "al. . the", ". the high", "the high affinity", "high affinity of", "affinity of il", "il 2 binding", "2 binding to", "binding to the", "to the il", "il 2r is", "2r is created", "is created by", "created by a", "by a very", "a very rapid", "very rapid association", "rapid association rate", "association rate to", "rate to the", "chain combined", "combined with a", "with a much", "a much slower", "much slower dissociation", "slower dissociation rate", "dissociation rate contributed", "rate contributed by", "contributed by the", "by the combination", "the combination of", "combination of the", "of the il", "il 2r beta", "2r beta and", "and gamma chains", "chains wang", "wang & smith", "& smith 1987", "smith 1987 .", "1987 . after", ". after antigen", "after antigen stimulation", "stimulation t", "t cells upregulate", "cells upregulate the", "upregulate the high", "affinity il 2r", "chain il", "2r alpha captures", "alpha captures il", "captures il 2", "il 2 and", "2 and this", "and this complex", "this complex then", "complex then associates", "then associates with", "associates with the", "with the constitutively", "the constitutively expressed", "constitutively expressed il", "expressed il 2r", "gamma chain is", "chain is shared", "is shared by", "shared by several", "by several other", "several other members", "other members of", "members of the", "of the cytokine", "the cytokine receptor", "cytokine receptor superfamily", "receptor superfamily including", "superfamily including il", "including il 4", "4 il", "7 il", "9 il", "il 15 and", "15 and il", "and il 21", "il 21 receptors", "receptors and", "and consequently is", "consequently is often", "is often referred", "often referred to", "referred to as", "to as the", "as the common", "the common gamma", "common gamma chain", "chain gamma", "gamma c .", "c . the", ". the tyrosine", "the tyrosine kinases", "tyrosine kinases jak1", "kinases jak1 and", "jak1 and jak3", "jak3 which", "which are constitutively", "are constitutively associated", "constitutively associated with", "associated with il", "with il 2r", "and gamma c", "gamma c respectively", "respectively are", "are activated resulting", "activated resulting in", "resulting in phosphorylation", "in phosphorylation of", "phosphorylation of three", "of three critical", "three critical tyrosine", "critical tyrosine residues", "tyrosine residues in", "residues in the", "in the il", "2r beta cytoplasmic", "beta cytoplasmic tail.", "cytoplasmic tail. these", "tail. these phosphorylated", "these phosphorylated residues", "phosphorylated residues enable", "residues enable recruitment", "enable recruitment of", "recruitment of the", "of the adaptor", "the adaptor molecule", "adaptor molecule shc", "shc activating", "activating the mapk", "the mapk and", "mapk and pi3k", "and pi3k pathways", "pathways and", "and the transcription", "the transcription factor", "transcription factor stat5.", "factor stat5. after", "stat5. after phosphorylation", "phosphorylation stat5", "stat5 forms dimers", "forms dimers that", "dimers that translocate", "that translocate to", "translocate to the", "to the nucleus", "the nucleus and", "nucleus and initiate", "and initiate gene", "initiate gene expression.", "gene expression. while", "expression. while stat5", "while stat5 activation", "stat5 activation is", "activation is critical", "critical for il", "for il 2", "il 2 function", "2 function in", "function in most", "in most cell", "most cell types", "types the", "the contribution of", "contribution of the", "of the pi3k/akt", "the pi3k/akt pathway", "pi3k/akt pathway differs", "pathway differs between", "differs between distinct", "between distinct t", "distinct t cell", "t cell subsets.", "cell subsets. in", "subsets. in tregs", "in tregs for", "tregs for example", "example pi3k/akt", "pi3k/akt is not", "is not involved", "not involved in", "involved in il", "in il 2", "il 2 signaling", "2 signaling and", "signaling and this", "and this may", "this may explain", "may explain some", "explain some of", "some of the", "of the different", "the different functional", "different functional outcomes", "functional outcomes of", "outcomes of il", "2 signaling in", "signaling in tregs", "in tregs vs.", "tregs vs. effector", "vs. effector t", "effector t cells.", "interleukin 2 il", "2 il 2", "2 is a", "is a cytokine that", "a cytokine that is", "cytokine that is produced", "that is produced by", "is produced by t", "produced by t cells", "by t cells in", "t cells in response", "cells in response to", "in response to antigen", "response to antigen stimulation.", "to antigen stimulation. originally", "stimulation. originally il", "originally il 2", "il 2 was discovered", "2 was discovered because", "was discovered because of", "discovered because of its", "because of its potent", "of its potent growth", "its potent growth factor", "potent growth factor activity", "growth factor activity on", "factor activity on activated", "activity on activated t", "on activated t cells", "activated t cells in", "t cells in vitro", "cells in vitro and", "in vitro and was", "vitro and was therefore", "and was therefore named", "was therefore named 't", "therefore named 't cell", "named 't cell growth", "'t cell growth factor'", "growth factor' tcgf", "factor' tcgf .", ". however the", "however the generation", "the generation of il", "generation of il 2", "2 and il", "and il 2 receptor", "il 2 receptor deficient", "2 receptor deficient mice", "receptor deficient mice revealed", "deficient mice revealed that", "mice revealed that il", "revealed that il 2", "that il 2 also", "il 2 also plays", "2 also plays a", "also plays a regulatory", "plays a regulatory role", "a regulatory role in", "regulatory role in the", "role in the immune", "in the immune system", "the immune system by", "immune system by suppressing", "system by suppressing autoimmune", "by suppressing autoimmune responses.", "suppressing autoimmune responses. two", "autoimmune responses. two main", "responses. two main mechanisms", "two main mechanisms have", "main mechanisms have been", "mechanisms have been identified", "have been identified that", "been identified that explain", "identified that explain this", "that explain this suppressive", "explain this suppressive function:", "suppressive function: 1", "1 il 2", "il 2 sensitizes activated", "2 sensitizes activated t", "sensitizes activated t cells", "activated t cells for", "t cells for activation", "cells for activation induced", "for activation induced cell", "activation induced cell death", "cell death aicd", "il 2 is critical", "2 is critical for", "is critical for the", "critical for the survival", "for the survival and", "the survival and function", "survival and function of", "and function of regulatory", "function of regulatory t", "of regulatory t cells", "t cells tregs", "tregs which", "which possess potent immunosuppressive", "possess potent immunosuppressive properties.

              il", "potent immunosuppressive properties.

              il 2", "immunosuppressive properties.

              il 2 signaling", "properties.

              il 2 signaling occurs", "2 signaling occurs when", "signaling occurs when il", "occurs when il 2", "when il 2 binds", "il 2 binds to", "2 binds to the", "binds to the heterotrimeric", "to the heterotrimeric high", "the heterotrimeric high affinity", "heterotrimeric high affinity il", "high affinity il 2", "affinity il 2 receptor", "2 receptor il", "receptor il 2r", "2r which", "which consists of alpha", "of alpha beta", "alpha beta and", "beta and gamma chains.", "and gamma chains. the", "gamma chains. the il", "chains. the il 2r", "the il 2r was", "il 2r was identified", "2r was identified in", "was identified in 1981", "identified in 1981 via", "in 1981 via radiolabeled", "1981 via radiolabeled ligand", "via radiolabeled ligand binding", "ligand binding robb", "binding robb et", "robb et al. 1981", "et al. 1981 .", "al. 1981 . the", "1981 . the il", ". the il 2r", "the il 2r alpha", "il 2r alpha chain", "2r alpha chain was", "chain was identified", "in 1982 leonard", "1982 leonard et", "al. the", "the beta chain in", "beta chain in 1986/7", "in 1986/7 sharon", "1986/7 sharon et", "sharon et al. 1986", "al. 1986 teshigawara", "1986 teshigawara et", "teshigawara et al. 1987", "al. 1987 and", "1987 and the", "and the il 2r", "the il 2r gamma", "il 2r gamma chain", "2r gamma chain in", "gamma chain in 1992", "in 1992 takeshita", "1992 takeshita et", "takeshita et al. .", "et al. . the", "al. . the high", ". the high affinity", "the high affinity of", "high affinity of il", "affinity of il 2", "of il 2 binding", "il 2 binding to", "2 binding to the", "binding to the il", "to the il 2r", "the il 2r is", "il 2r is created", "2r is created by", "is created by a", "created by a very", "by a very rapid", "a very rapid association", "very rapid association rate", "rapid association rate to", "association rate to the", "rate to the il", "alpha chain combined", "chain combined with", "combined with a much", "with a much slower", "a much slower dissociation", "much slower dissociation rate", "slower dissociation rate contributed", "dissociation rate contributed by", "rate contributed by the", "contributed by the combination", "by the combination of", "the combination of the", "combination of the il", "of the il 2r", "the il 2r beta", "il 2r beta and", "2r beta and gamma", "beta and gamma chains", "gamma chains wang", "chains wang &", "wang & smith 1987", "& smith 1987 .", "smith 1987 . after", "1987 . after antigen", ". after antigen stimulation", "antigen stimulation t", "stimulation t cells", "t cells upregulate the", "cells upregulate the high", "upregulate the high affinity", "the high affinity il", "high affinity il 2r", "affinity il 2r alpha", "alpha chain il", "chain il 2r", "il 2r alpha captures", "2r alpha captures il", "alpha captures il 2", "captures il 2 and", "il 2 and this", "2 and this complex", "and this complex then", "this complex then associates", "complex then associates with", "then associates with the", "associates with the constitutively", "with the constitutively expressed", "the constitutively expressed il", "constitutively expressed il 2r", "expressed il 2r beta", "2r gamma chain is", "gamma chain is shared", "chain is shared by", "is shared by several", "shared by several other", "by several other members", "several other members of", "other members of the", "members of the cytokine", "of the cytokine receptor", "the cytokine receptor superfamily", "cytokine receptor superfamily including", "receptor superfamily including il", "superfamily including il 4", "il 4 il", "4 il 7", "il 7 il", "7 il 9", "il 9 il", "9 il 15", "il 15 and il", "15 and il 21", "and il 21 receptors", "21 receptors and", "receptors and consequently", "and consequently is often", "consequently is often referred", "is often referred to", "often referred to as", "referred to as the", "to as the common", "as the common gamma", "the common gamma chain", "gamma chain gamma", "chain gamma c", "gamma c . the", "c . the tyrosine", ". the tyrosine kinases", "the tyrosine kinases jak1", "tyrosine kinases jak1 and", "kinases jak1 and jak3", "and jak3 which", "jak3 which are", "which are constitutively associated", "are constitutively associated with", "constitutively associated with il", "associated with il 2r", "with il 2r beta", "beta and gamma c", "and gamma c respectively", "c respectively are", "respectively are activated", "are activated resulting in", "activated resulting in phosphorylation", "resulting in phosphorylation of", "in phosphorylation of three", "phosphorylation of three critical", "of three critical tyrosine", "three critical tyrosine residues", "critical tyrosine residues in", "tyrosine residues in the", "residues in the il", "in the il 2r", "il 2r beta cytoplasmic", "2r beta cytoplasmic tail.", "beta cytoplasmic tail. these", "cytoplasmic tail. these phosphorylated", "tail. these phosphorylated residues", "these phosphorylated residues enable", "phosphorylated residues enable recruitment", "residues enable recruitment of", "enable recruitment of the", "recruitment of the adaptor", "of the adaptor molecule", "the adaptor molecule shc", "molecule shc activating", "shc activating the", "activating the mapk and", "the mapk and pi3k", "mapk and pi3k pathways", "pi3k pathways and", "pathways and the", "and the transcription factor", "the transcription factor stat5.", "transcription factor stat5. after", "factor stat5. after phosphorylation", "after phosphorylation stat5", "phosphorylation stat5 forms", "stat5 forms dimers that", "forms dimers that translocate", "dimers that translocate to", "that translocate to the", "translocate to the nucleus", "to the nucleus and", "the nucleus and initiate", "nucleus and initiate gene", "and initiate gene expression.", "initiate gene expression. while", "gene expression. while stat5", "expression. while stat5 activation", "while stat5 activation is", "stat5 activation is critical", "activation is critical for", "is critical for il", "critical for il 2", "for il 2 function", "il 2 function in", "2 function in most", "function in most cell", "in most cell types", "cell types the", "types the contribution", "the contribution of the", "contribution of the pi3k/akt", "of the pi3k/akt pathway", "the pi3k/akt pathway differs", "pi3k/akt pathway differs between", "pathway differs between distinct", "differs between distinct t", "between distinct t cell", "distinct t cell subsets.", "t cell subsets. in", "cell subsets. in tregs", "subsets. in tregs for", "in tregs for example", "for example pi3k/akt", "example pi3k/akt is", "pi3k/akt is not involved", "is not involved in", "not involved in il", "involved in il 2", "in il 2 signaling", "il 2 signaling and", "2 signaling and this", "signaling and this may", "and this may explain", "this may explain some", "may explain some of", "explain some of the", "some of the different", "of the different functional", "the different functional outcomes", "different functional outcomes of", "functional outcomes of il", "outcomes of il 2", "of il 2 signaling", "il 2 signaling in", "2 signaling in tregs", "signaling in tregs vs.", "in tregs vs. effector", "tregs vs. effector t", "vs. effector t cells.", "interleukin 2 il 2", "il 2 is a", "2 is a cytokine", "is a cytokine that is", "a cytokine that is produced", "cytokine that is produced by", "that is produced by t", "is produced by t cells", "produced by t cells in", "by t cells in response", "t cells in response to", "cells in response to antigen", "in response to antigen stimulation.", "response to antigen stimulation. originally", "antigen stimulation. originally il", "stimulation. originally il 2", "originally il 2 was", "il 2 was discovered because", "2 was discovered because of", "was discovered because of its", "discovered because of its potent", "because of its potent growth", "of its potent growth factor", "its potent growth factor activity", "potent growth factor activity on", "growth factor activity on activated", "factor activity on activated t", "activity on activated t cells", "on activated t cells in", "activated t cells in vitro", "t cells in vitro and", "cells in vitro and was", "in vitro and was therefore", "vitro and was therefore named", "and was therefore named 't", "was therefore named 't cell", "therefore named 't cell growth", "named 't cell growth factor'", "cell growth factor' tcgf", "growth factor' tcgf .", "factor' tcgf . however", "tcgf . however the", ". however the generation", "however the generation of", "the generation of il 2", "of il 2 and", "il 2 and il", "2 and il 2", "and il 2 receptor deficient", "il 2 receptor deficient mice", "2 receptor deficient mice revealed", "receptor deficient mice revealed that", "deficient mice revealed that il", "mice revealed that il 2", "revealed that il 2 also", "that il 2 also plays", "il 2 also plays a", "2 also plays a regulatory", "also plays a regulatory role", "plays a regulatory role in", "a regulatory role in the", "regulatory role in the immune", "role in the immune system", "in the immune system by", "the immune system by suppressing", "immune system by suppressing autoimmune", "system by suppressing autoimmune responses.", "by suppressing autoimmune responses. two", "suppressing autoimmune responses. two main", "autoimmune responses. two main mechanisms", "responses. two main mechanisms have", "two main mechanisms have been", "main mechanisms have been identified", "mechanisms have been identified that", "have been identified that explain", "been identified that explain this", "identified that explain this suppressive", "that explain this suppressive function:", "this suppressive function: 1", "function: 1 il", "1 il 2 sensitizes", "il 2 sensitizes activated t", "2 sensitizes activated t cells", "sensitizes activated t cells for", "activated t cells for activation", "t cells for activation induced", "cells for activation induced cell", "for activation induced cell death", "induced cell death aicd", "death aicd and", "aicd and 2", "and 2 il", "2 il 2 is", "il 2 is critical for", "2 is critical for the", "is critical for the survival", "critical for the survival and", "for the survival and function", "the survival and function of", "survival and function of regulatory", "and function of regulatory t", "function of regulatory t cells", "regulatory t cells tregs", "tregs which possess", "which possess potent immunosuppressive properties.

              il", "possess potent immunosuppressive properties.

              il 2", "potent immunosuppressive properties.

              il 2 signaling", "immunosuppressive properties.

              il 2 signaling occurs", "properties.

              il 2 signaling occurs when", "2 signaling occurs when il", "signaling occurs when il 2", "occurs when il 2 binds", "when il 2 binds to", "il 2 binds to the", "2 binds to the heterotrimeric", "binds to the heterotrimeric high", "to the heterotrimeric high affinity", "the heterotrimeric high affinity il", "heterotrimeric high affinity il 2", "high affinity il 2 receptor", "il 2 receptor il", "2 receptor il 2r", "il 2r which", "2r which consists", "consists of alpha beta", "of alpha beta and", "alpha beta and gamma", "beta and gamma chains. the", "and gamma chains. the il", "gamma chains. the il 2r", "chains. the il 2r was", "the il 2r was identified", "il 2r was identified in", "2r was identified in 1981", "was identified in 1981 via", "identified in 1981 via radiolabeled", "in 1981 via radiolabeled ligand", "1981 via radiolabeled ligand binding", "radiolabeled ligand binding robb", "ligand binding robb et", "binding robb et al.", "robb et al. 1981 .", "et al. 1981 . the", "al. 1981 . the il", "1981 . the il 2r", ". the il 2r alpha", "the il 2r alpha chain", "il 2r alpha chain was", "alpha chain was identified", "chain was identified in", "was identified in 1982", "identified in 1982 leonard", "in 1982 leonard et", "1982 leonard et al.", "et al. the", "al. the beta", "the beta chain in 1986/7", "chain in 1986/7 sharon", "in 1986/7 sharon et", "1986/7 sharon et al.", "et al. 1986 teshigawara", "al. 1986 teshigawara et", "1986 teshigawara et al.", "et al. 1987 and", "al. 1987 and the", "1987 and the il", "and the il 2r gamma", "the il 2r gamma chain", "il 2r gamma chain in", "2r gamma chain in 1992", "chain in 1992 takeshita", "in 1992 takeshita et", "1992 takeshita et al.", "takeshita et al. . the", "et al. . the high", "al. . the high affinity", ". the high affinity of", "the high affinity of il", "high affinity of il 2", "affinity of il 2 binding", "of il 2 binding to", "il 2 binding to the", "2 binding to the il", "binding to the il 2r", "to the il 2r is", "the il 2r is created", "il 2r is created by", "2r is created by a", "is created by a very", "created by a very rapid", "by a very rapid association", "a very rapid association rate", "very rapid association rate to", "rapid association rate to the", "association rate to the il", "rate to the il 2r", "to the il 2r alpha", "2r alpha chain combined", "alpha chain combined with", "chain combined with a", "combined with a much slower", "with a much slower dissociation", "a much slower dissociation rate", "much slower dissociation rate contributed", "slower dissociation rate contributed by", "dissociation rate contributed by the", "rate contributed by the combination", "contributed by the combination of", "by the combination of the", "the combination of the il", "combination of the il 2r", "of the il 2r beta", "the il 2r beta and", "il 2r beta and gamma", "2r beta and gamma chains", "and gamma chains wang", "gamma chains wang &", "chains wang & smith", "wang & smith 1987 .", "& smith 1987 . after", "smith 1987 . after antigen", "1987 . after antigen stimulation", "after antigen stimulation t", "antigen stimulation t cells", "stimulation t cells upregulate", "t cells upregulate the high", "cells upregulate the high affinity", "upregulate the high affinity il", "the high affinity il 2r", "high affinity il 2r alpha", "affinity il 2r alpha chain", "2r alpha chain il", "alpha chain il 2r", "chain il 2r alpha", "il 2r alpha captures il", "2r alpha captures il 2", "alpha captures il 2 and", "captures il 2 and this", "il 2 and this complex", "2 and this complex then", "and this complex then associates", "this complex then associates with", "complex then associates with the", "then associates with the constitutively", "associates with the constitutively expressed", "with the constitutively expressed il", "the constitutively expressed il 2r", "constitutively expressed il 2r beta", "expressed il 2r beta and", "2r beta and gamma chains.", "il 2r gamma chain is", "2r gamma chain is shared", "gamma chain is shared by", "chain is shared by several", "is shared by several other", "shared by several other members", "by several other members of", "several other members of the", "other members of the cytokine", "members of the cytokine receptor", "of the cytokine receptor superfamily", "the cytokine receptor superfamily including", "cytokine receptor superfamily including il", "receptor superfamily including il 4", "including il 4 il", "il 4 il 7", "il 7 il 9", "il 9 il 15", "9 il 15 and", "il 15 and il 21", "15 and il 21 receptors", "il 21 receptors and", "21 receptors and consequently", "receptors and consequently is", "and consequently is often referred", "consequently is often referred to", "is often referred to as", "often referred to as the", "referred to as the common", "to as the common gamma", "as the common gamma chain", "common gamma chain gamma", "gamma chain gamma c", "chain gamma c .", "gamma c . the tyrosine", "c . the tyrosine kinases", ". the tyrosine kinases jak1", "the tyrosine kinases jak1 and", "tyrosine kinases jak1 and jak3", "jak1 and jak3 which", "and jak3 which are", "jak3 which are constitutively", "which are constitutively associated with", "are constitutively associated with il", "constitutively associated with il 2r", "associated with il 2r beta", "with il 2r beta and", "2r beta and gamma c", "beta and gamma c respectively", "gamma c respectively are", "c respectively are activated", "respectively are activated resulting", "are activated resulting in phosphorylation", "activated resulting in phosphorylation of", "resulting in phosphorylation of three", "in phosphorylation of three critical", "phosphorylation of three critical tyrosine", "of three critical tyrosine residues", "three critical tyrosine residues in", "critical tyrosine residues in the", "tyrosine residues in the il", "residues in the il 2r", "in the il 2r beta", "the il 2r beta cytoplasmic", "il 2r beta cytoplasmic tail.", "2r beta cytoplasmic tail. these", "beta cytoplasmic tail. these phosphorylated", "cytoplasmic tail. these phosphorylated residues", "tail. these phosphorylated residues enable", "these phosphorylated residues enable recruitment", "phosphorylated residues enable recruitment of", "residues enable recruitment of the", "enable recruitment of the adaptor", "recruitment of the adaptor molecule", "of the adaptor molecule shc", "adaptor molecule shc activating", "molecule shc activating the", "shc activating the mapk", "activating the mapk and pi3k", "the mapk and pi3k pathways", "and pi3k pathways and", "pi3k pathways and the", "pathways and the transcription", "and the transcription factor stat5.", "the transcription factor stat5. after", "transcription factor stat5. after phosphorylation", "stat5. after phosphorylation stat5", "after phosphorylation stat5 forms", "phosphorylation stat5 forms dimers", "stat5 forms dimers that translocate", "forms dimers that translocate to", "dimers that translocate to the", "that translocate to the nucleus", "translocate to the nucleus and", "to the nucleus and initiate", "the nucleus and initiate gene", "nucleus and initiate gene expression.", "and initiate gene expression. while", "initiate gene expression. while stat5", "gene expression. while stat5 activation", "expression. while stat5 activation is", "while stat5 activation is critical", "stat5 activation is critical for", "activation is critical for il", "is critical for il 2", "critical for il 2 function", "for il 2 function in", "il 2 function in most", "2 function in most cell", "function in most cell types", "most cell types the", "cell types the contribution", "types the contribution of", "the contribution of the pi3k/akt", "contribution of the pi3k/akt pathway", "of the pi3k/akt pathway differs", "the pi3k/akt pathway differs between", "pi3k/akt pathway differs between distinct", "pathway differs between distinct t", "differs between distinct t cell", "between distinct t cell subsets.", "distinct t cell subsets. in", "t cell subsets. in tregs", "cell subsets. in tregs for", "subsets. in tregs for example", "tregs for example pi3k/akt", "for example pi3k/akt is", "example pi3k/akt is not", "pi3k/akt is not involved in", "is not involved in il", "not involved in il 2", "involved in il 2 signaling", "in il 2 signaling and", "il 2 signaling and this", "2 signaling and this may", "signaling and this may explain", "and this may explain some", "this may explain some of", "may explain some of the", "explain some of the different", "some of the different functional", "of the different functional outcomes", "the different functional outcomes of", "different functional outcomes of il", "functional outcomes of il 2", "outcomes of il 2 signaling", "of il 2 signaling in", "il 2 signaling in tregs", "2 signaling in tregs vs.", "signaling in tregs vs. effector", "in tregs vs. effector t", "tregs vs. effector t cells." ] }, { "record_id": "GLY_000594_1_1192", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020591", "r hsa", "hsa 9020591", "r hsa 9020591" ] }, { "record_id": "GLY_000594_1_1192", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 12", "12 signaling", "interleukin 12 signaling", "il 12", "is heterodimeric", "heterodimeric cytokine", "cytokine produced", "produced by", "by dendritic", "dendritic cells", "macrophages and", "and neutrophils.", "neutrophils. it", "it is", "is encoded", "encoded by", "by the", "the genes", "genes interleukin", "12 subunit", "subunit alpha", "and interleukin", "subunit beta", "which encode", "encode a", "a 35", "35 kda", "kda light", "light chain", "and a", "a 40", "40 kda", "kda heavy", "heavy chain", "respectively. the", "the active", "active il12", "il12 heterodimer", "heterodimer is", "is sometimes", "sometimes referred", "referred to", "to as", "as p70.", "p70. the", "the p35", "p35 component", "component has", "has homology", "homology to", "to single", "single chain", "chain cytokines", "while p40", "p40 is", "is homologous", "homologous to", "to the", "the extracellular", "extracellular domains", "domains of", "of members", "members of", "of the", "the haematopoietic", "haematopoietic cytokine", "cytokine receptor", "receptor family.", "family. the", "the il12", "heterodimer therefore", "therefore resembles", "resembles a", "a cytokine", "cytokine linked", "linked to", "to a", "a soluble", "soluble receptor.", "receptor. il12", "il12 is", "is involved", "involved in", "in the", "the differentiation", "differentiation of", "of naive", "naive t", "t cells", "cells into", "into th1", "th1 cells", "cells and", "and sometimes", "sometimes known", "known as", "as t", "t cell", "cell stimulating", "stimulating factor.", "factor. il12", "il12 enhances", "enhances the", "the cytotoxic", "cytotoxic activity", "activity of", "of natural", "natural killer", "killer cells", "and cd8+", "cd8+ cytotoxic", "cytotoxic t", "t lymphocytes.", "lymphocytes. il12", "il12 also", "also has", "has anti", "anti angiogenic", "angiogenic activity", "mediated by", "by increased", "increased production", "production of", "of cxcl10", "cxcl10 via", "via interferon", "interferon gamma.", "gamma. the", "il12 receptor", "receptor is", "is a", "a heterodimer", "heterodimer formed", "formed by", "by interleukin", "12 receptor", "receptor subunit", "beta 1", "beta 2", "both of", "of which", "which have", "have extensive", "extensive homology", "to il6st", "the signal", "signal transducing", "transducing receptor", "subunit of", "the il6", "il6 like", "like cytokine", "cytokine superfamily.", "superfamily. il", "il 12rb2", "12rb2 is", "is considered", "considered to", "to play", "play the", "the key", "key role", "role in", "in il12", "il12 function", "in part", "part because", "because its", "its expression", "expression on", "on activated", "activated t", "cells is", "is stimulated", "stimulated by", "by cytokines", "cytokines that", "that promote", "promote th1", "th1 cell", "cell development", "development and", "and inhibited", "inhibited by", "by those", "those that", "promote th2", "th2 cells", "cells development.", "development. in", "in addition", "il12 binding", "binding leads", "leads to", "to il12rb2", "il12rb2 tyrosine", "tyrosine phosphorylation", "which provides", "provides binding", "binding sites", "sites for", "for the", "the kinases", "kinases non", "non receptor", "receptor tyrosine", "tyrosine protein", "protein kinase", "kinase tyk2", "tyk2 and", "and tyrosine", "kinase jak2.", "jak2. these", "these activate", "activate transcription", "transcription factor", "factor proteins", "proteins in", "signal transducer", "transducer and", "and activator", "activator of", "of transcription", "particularly stat4.", "12 il", "12 is", "is heterodimeric cytokine", "heterodimeric cytokine produced", "cytokine produced by", "produced by dendritic", "by dendritic cells", "cells macrophages", "macrophages and neutrophils.", "and neutrophils. it", "neutrophils. it is", "it is encoded", "is encoded by", "encoded by the", "by the genes", "the genes interleukin", "genes interleukin 12", "interleukin 12 subunit", "12 subunit alpha", "alpha il12a", "il12a and", "and interleukin 12", "12 subunit beta", "beta il12b", "which encode a", "encode a 35", "a 35 kda", "35 kda light", "kda light chain", "chain p35", "p35 and", "and a 40", "a 40 kda", "40 kda heavy", "kda heavy chain", "chain p40", "respectively. the active", "the active il12", "active il12 heterodimer", "il12 heterodimer is", "heterodimer is sometimes", "is sometimes referred", "sometimes referred to", "referred to as", "to as p70.", "as p70. the", "p70. the p35", "the p35 component", "p35 component has", "component has homology", "has homology to", "homology to single", "to single chain", "single chain cytokines", "cytokines while", "while p40 is", "p40 is homologous", "is homologous to", "homologous to the", "to the extracellular", "the extracellular domains", "extracellular domains of", "domains of members", "of members of", "members of the", "of the haematopoietic", "the haematopoietic cytokine", "haematopoietic cytokine receptor", "cytokine receptor family.", "receptor family. the", "family. the il12", "the il12 heterodimer", "il12 heterodimer therefore", "heterodimer therefore resembles", "therefore resembles a", "resembles a cytokine", "a cytokine linked", "cytokine linked to", "linked to a", "to a soluble", "a soluble receptor.", "soluble receptor. il12", "receptor. il12 is", "il12 is involved", "is involved in", "involved in the", "in the differentiation", "the differentiation of", "differentiation of naive", "of naive t", "naive t cells", "t cells into", "cells into th1", "into th1 cells", "th1 cells and", "cells and sometimes", "and sometimes known", "sometimes known as", "known as t", "as t cell", "t cell stimulating", "cell stimulating factor.", "stimulating factor. il12", "factor. il12 enhances", "il12 enhances the", "enhances the cytotoxic", "the cytotoxic activity", "cytotoxic activity of", "activity of natural", "of natural killer", "natural killer cells", "killer cells and", "cells and cd8+", "and cd8+ cytotoxic", "cd8+ cytotoxic t", "cytotoxic t lymphocytes.", "t lymphocytes. il12", "lymphocytes. il12 also", "il12 also has", "also has anti", "has anti angiogenic", "anti angiogenic activity", "activity mediated", "mediated by increased", "by increased production", "increased production of", "production of cxcl10", "of cxcl10 via", "cxcl10 via interferon", "via interferon gamma.", "interferon gamma. the", "gamma. the il12", "the il12 receptor", "il12 receptor is", "receptor is a", "is a heterodimer", "a heterodimer formed", "heterodimer formed by", "formed by interleukin", "by interleukin 12", "interleukin 12 receptor", "12 receptor subunit", "receptor subunit beta", "subunit beta 1", "1 il12rb1", "il12rb1 and", "subunit beta 2", "2 il12rb2", "both of which", "of which have", "which have extensive", "have extensive homology", "extensive homology to", "homology to il6st", "il6st gp130", "the signal transducing", "signal transducing receptor", "transducing receptor subunit", "receptor subunit of", "subunit of the", "of the il6", "the il6 like", "il6 like cytokine", "like cytokine superfamily.", "cytokine superfamily. il", "superfamily. il 12rb2", "il 12rb2 is", "12rb2 is considered", "is considered to", "considered to play", "to play the", "play the key", "the key role", "key role in", "role in il12", "in il12 function", "function in", "in part because", "part because its", "because its expression", "its expression on", "expression on activated", "on activated t", "activated t cells", "t cells is", "cells is stimulated", "is stimulated by", "stimulated by cytokines", "by cytokines that", "cytokines that promote", "that promote th1", "promote th1 cell", "th1 cell development", "cell development and", "development and inhibited", "and inhibited by", "inhibited by those", "by those that", "those that promote", "that promote th2", "promote th2 cells", "th2 cells development.", "cells development. in", "development. in addition", "addition il12", "il12 binding leads", "binding leads to", "leads to il12rb2", "to il12rb2 tyrosine", "il12rb2 tyrosine phosphorylation", "phosphorylation which", "which provides binding", "provides binding sites", "binding sites for", "sites for the", "for the kinases", "the kinases non", "kinases non receptor", "non receptor tyrosine", "receptor tyrosine protein", "tyrosine protein kinase", "protein kinase tyk2", "kinase tyk2 and", "tyk2 and tyrosine", "and tyrosine protein", "protein kinase jak2.", "kinase jak2. these", "jak2. these activate", "these activate transcription", "activate transcription factor", "transcription factor proteins", "factor proteins in", "proteins in the", "in the signal", "the signal transducer", "signal transducer and", "transducer and activator", "and activator of", "activator of transcription", "transcription stat", "stat family", "family particularly", "interleukin 12 il", "12 il 12", "il 12 is", "12 is heterodimeric", "is heterodimeric cytokine produced", "heterodimeric cytokine produced by", "cytokine produced by dendritic", "produced by dendritic cells", "dendritic cells macrophages", "cells macrophages and", "macrophages and neutrophils. it", "and neutrophils. it is", "neutrophils. it is encoded", "it is encoded by", "is encoded by the", "encoded by the genes", "by the genes interleukin", "the genes interleukin 12", "genes interleukin 12 subunit", "interleukin 12 subunit alpha", "subunit alpha il12a", "il12a and interleukin", "and interleukin 12 subunit", "interleukin 12 subunit beta", "subunit beta il12b", "il12b which", "which encode a 35", "encode a 35 kda", "a 35 kda light", "35 kda light chain", "light chain p35", "p35 and a", "and a 40 kda", "a 40 kda heavy", "40 kda heavy chain", "heavy chain p40", "p40 respectively.", "respectively. the active il12", "the active il12 heterodimer", "active il12 heterodimer is", "il12 heterodimer is sometimes", "heterodimer is sometimes referred", "is sometimes referred to", "sometimes referred to as", "referred to as p70.", "to as p70. the", "as p70. the p35", "p70. the p35 component", "the p35 component has", "p35 component has homology", "component has homology to", "has homology to single", "homology to single chain", "to single chain cytokines", "chain cytokines while", "cytokines while p40", "while p40 is homologous", "p40 is homologous to", "is homologous to the", "homologous to the extracellular", "to the extracellular domains", "the extracellular domains of", "extracellular domains of members", "domains of members of", "of members of the", "members of the haematopoietic", "of the haematopoietic cytokine", "the haematopoietic cytokine receptor", "haematopoietic cytokine receptor family.", "cytokine receptor family. the", "receptor family. the il12", "family. the il12 heterodimer", "the il12 heterodimer therefore", "il12 heterodimer therefore resembles", "heterodimer therefore resembles a", "therefore resembles a cytokine", "resembles a cytokine linked", "a cytokine linked to", "cytokine linked to a", "linked to a soluble", "to a soluble receptor.", "a soluble receptor. il12", "soluble receptor. il12 is", "receptor. il12 is involved", "il12 is involved in", "is involved in the", "involved in the differentiation", "in the differentiation of", "the differentiation of naive", "differentiation of naive t", "of naive t cells", "naive t cells into", "t cells into th1", "cells into th1 cells", "into th1 cells and", "th1 cells and sometimes", "cells and sometimes known", "and sometimes known as", "sometimes known as t", "known as t cell", "as t cell stimulating", "t cell stimulating factor.", "cell stimulating factor. il12", "stimulating factor. il12 enhances", "factor. il12 enhances the", "il12 enhances the cytotoxic", "enhances the cytotoxic activity", "the cytotoxic activity of", "cytotoxic activity of natural", "activity of natural killer", "of natural killer cells", "natural killer cells and", "killer cells and cd8+", "cells and cd8+ cytotoxic", "and cd8+ cytotoxic t", "cd8+ cytotoxic t lymphocytes.", "cytotoxic t lymphocytes. il12", "t lymphocytes. il12 also", "lymphocytes. il12 also has", "il12 also has anti", "also has anti angiogenic", "has anti angiogenic activity", "angiogenic activity mediated", "activity mediated by", "mediated by increased production", "by increased production of", "increased production of cxcl10", "production of cxcl10 via", "of cxcl10 via interferon", "cxcl10 via interferon gamma.", "via interferon gamma. the", "interferon gamma. the il12", "gamma. the il12 receptor", "the il12 receptor is", "il12 receptor is a", "receptor is a heterodimer", "is a heterodimer formed", "a heterodimer formed by", "heterodimer formed by interleukin", "formed by interleukin 12", "by interleukin 12 receptor", "interleukin 12 receptor subunit", "12 receptor subunit beta", "receptor subunit beta 1", "beta 1 il12rb1", "il12rb1 and interleukin", "and interleukin 12 receptor", "receptor subunit beta 2", "beta 2 il12rb2", "il12rb2 both", "both of which have", "of which have extensive", "which have extensive homology", "have extensive homology to", "extensive homology to il6st", "to il6st gp130", "gp130 the", "the signal transducing receptor", "signal transducing receptor subunit", "transducing receptor subunit of", "receptor subunit of the", "subunit of the il6", "of the il6 like", "the il6 like cytokine", "il6 like cytokine superfamily.", "like cytokine superfamily. il", "cytokine superfamily. il 12rb2", "superfamily. il 12rb2 is", "il 12rb2 is considered", "12rb2 is considered to", "is considered to play", "considered to play the", "to play the key", "play the key role", "the key role in", "key role in il12", "role in il12 function", "il12 function in", "function in part", "in part because its", "part because its expression", "because its expression on", "its expression on activated", "expression on activated t", "on activated t cells", "activated t cells is", "t cells is stimulated", "cells is stimulated by", "is stimulated by cytokines", "stimulated by cytokines that", "by cytokines that promote", "cytokines that promote th1", "that promote th1 cell", "promote th1 cell development", "th1 cell development and", "cell development and inhibited", "development and inhibited by", "and inhibited by those", "inhibited by those that", "by those that promote", "those that promote th2", "that promote th2 cells", "promote th2 cells development.", "th2 cells development. in", "cells development. in addition", "in addition il12", "addition il12 binding", "il12 binding leads to", "binding leads to il12rb2", "leads to il12rb2 tyrosine", "to il12rb2 tyrosine phosphorylation", "tyrosine phosphorylation which", "phosphorylation which provides", "which provides binding sites", "provides binding sites for", "binding sites for the", "sites for the kinases", "for the kinases non", "the kinases non receptor", "kinases non receptor tyrosine", "non receptor tyrosine protein", "receptor tyrosine protein kinase", "tyrosine protein kinase tyk2", "protein kinase tyk2 and", "kinase tyk2 and tyrosine", "tyk2 and tyrosine protein", "and tyrosine protein kinase", "tyrosine protein kinase jak2.", "protein kinase jak2. these", "kinase jak2. these activate", "jak2. these activate transcription", "these activate transcription factor", "activate transcription factor proteins", "transcription factor proteins in", "factor proteins in the", "proteins in the signal", "in the signal transducer", "the signal transducer and", "signal transducer and activator", "transducer and activator of", "and activator of transcription", "of transcription stat", "family particularly stat4.", "interleukin 12 il 12", "il 12 is heterodimeric", "12 is heterodimeric cytokine", "is heterodimeric cytokine produced by", "heterodimeric cytokine produced by dendritic", "cytokine produced by dendritic cells", "by dendritic cells macrophages", "dendritic cells macrophages and", "cells macrophages and neutrophils.", "macrophages and neutrophils. it is", "and neutrophils. it is encoded", "neutrophils. it is encoded by", "it is encoded by the", "is encoded by the genes", "encoded by the genes interleukin", "by the genes interleukin 12", "the genes interleukin 12 subunit", "genes interleukin 12 subunit alpha", "12 subunit alpha il12a", "alpha il12a and", "il12a and interleukin 12", "and interleukin 12 subunit beta", "12 subunit beta il12b", "il12b which encode", "which encode a 35 kda", "encode a 35 kda light", "a 35 kda light chain", "kda light chain p35", "chain p35 and", "p35 and a 40", "and a 40 kda heavy", "a 40 kda heavy chain", "kda heavy chain p40", "p40 respectively. the", "respectively. the active il12 heterodimer", "the active il12 heterodimer is", "active il12 heterodimer is sometimes", "il12 heterodimer is sometimes referred", "heterodimer is sometimes referred to", "is sometimes referred to as", "sometimes referred to as p70.", "referred to as p70. the", "to as p70. the p35", "as p70. the p35 component", "p70. the p35 component has", "the p35 component has homology", "p35 component has homology to", "component has homology to single", "has homology to single chain", "homology to single chain cytokines", "single chain cytokines while", "chain cytokines while p40", "cytokines while p40 is", "while p40 is homologous to", "p40 is homologous to the", "is homologous to the extracellular", "homologous to the extracellular domains", "to the extracellular domains of", "the extracellular domains of members", "extracellular domains of members of", "domains of members of the", "of members of the haematopoietic", "members of the haematopoietic cytokine", "of the haematopoietic cytokine receptor", "the haematopoietic cytokine receptor family.", "haematopoietic cytokine receptor family. the", "cytokine receptor family. the il12", "receptor family. the il12 heterodimer", "family. the il12 heterodimer therefore", "the il12 heterodimer therefore resembles", "il12 heterodimer therefore resembles a", "heterodimer therefore resembles a cytokine", "therefore resembles a cytokine linked", "resembles a cytokine linked to", "a cytokine linked to a", "cytokine linked to a soluble", "linked to a soluble receptor.", "to a soluble receptor. il12", "a soluble receptor. il12 is", "soluble receptor. il12 is involved", "receptor. il12 is involved in", "il12 is involved in the", "is involved in the differentiation", "involved in the differentiation of", "in the differentiation of naive", "the differentiation of naive t", "differentiation of naive t cells", "of naive t cells into", "naive t cells into th1", "t cells into th1 cells", "cells into th1 cells and", "into th1 cells and sometimes", "th1 cells and sometimes known", "cells and sometimes known as", "and sometimes known as t", "sometimes known as t cell", "known as t cell stimulating", "as t cell stimulating factor.", "t cell stimulating factor. il12", "cell stimulating factor. il12 enhances", "stimulating factor. il12 enhances the", "factor. il12 enhances the cytotoxic", "il12 enhances the cytotoxic activity", "enhances the cytotoxic activity of", "the cytotoxic activity of natural", "cytotoxic activity of natural killer", "activity of natural killer cells", "of natural killer cells and", "natural killer cells and cd8+", "killer cells and cd8+ cytotoxic", "cells and cd8+ cytotoxic t", "and cd8+ cytotoxic t lymphocytes.", "cd8+ cytotoxic t lymphocytes. il12", "cytotoxic t lymphocytes. il12 also", "t lymphocytes. il12 also has", "lymphocytes. il12 also has anti", "il12 also has anti angiogenic", "also has anti angiogenic activity", "anti angiogenic activity mediated", "angiogenic activity mediated by", "activity mediated by increased", "mediated by increased production of", "by increased production of cxcl10", "increased production of cxcl10 via", "production of cxcl10 via interferon", "of cxcl10 via interferon gamma.", "cxcl10 via interferon gamma. the", "via interferon gamma. the il12", "interferon gamma. the il12 receptor", "gamma. the il12 receptor is", "the il12 receptor is a", "il12 receptor is a heterodimer", "receptor is a heterodimer formed", "is a heterodimer formed by", "a heterodimer formed by interleukin", "heterodimer formed by interleukin 12", "formed by interleukin 12 receptor", "by interleukin 12 receptor subunit", "interleukin 12 receptor subunit beta", "12 receptor subunit beta 1", "subunit beta 1 il12rb1", "1 il12rb1 and", "il12rb1 and interleukin 12", "and interleukin 12 receptor subunit", "12 receptor subunit beta 2", "subunit beta 2 il12rb2", "il12rb2 both of", "both of which have extensive", "of which have extensive homology", "which have extensive homology to", "have extensive homology to il6st", "homology to il6st gp130", "gp130 the signal", "the signal transducing receptor subunit", "signal transducing receptor subunit of", "transducing receptor subunit of the", "receptor subunit of the il6", "subunit of the il6 like", "of the il6 like cytokine", "the il6 like cytokine superfamily.", "il6 like cytokine superfamily. il", "like cytokine superfamily. il 12rb2", "cytokine superfamily. il 12rb2 is", "superfamily. il 12rb2 is considered", "il 12rb2 is considered to", "12rb2 is considered to play", "is considered to play the", "considered to play the key", "to play the key role", "play the key role in", "the key role in il12", "key role in il12 function", "in il12 function in", "il12 function in part", "function in part because", "in part because its expression", "part because its expression on", "because its expression on activated", "its expression on activated t", "expression on activated t cells", "on activated t cells is", "activated t cells is stimulated", "t cells is stimulated by", "cells is stimulated by cytokines", "is stimulated by cytokines that", "stimulated by cytokines that promote", "by cytokines that promote th1", "cytokines that promote th1 cell", "that promote th1 cell development", "promote th1 cell development and", "th1 cell development and inhibited", "cell development and inhibited by", "development and inhibited by those", "and inhibited by those that", "inhibited by those that promote", "by those that promote th2", "those that promote th2 cells", "that promote th2 cells development.", "promote th2 cells development. in", "th2 cells development. in addition", "development. in addition il12", "in addition il12 binding", "addition il12 binding leads", "il12 binding leads to il12rb2", "binding leads to il12rb2 tyrosine", "leads to il12rb2 tyrosine phosphorylation", "il12rb2 tyrosine phosphorylation which", "tyrosine phosphorylation which provides", "phosphorylation which provides binding", "which provides binding sites for", "provides binding sites for the", "binding sites for the kinases", "sites for the kinases non", "for the kinases non receptor", "the kinases non receptor tyrosine", "kinases non receptor tyrosine protein", "non receptor tyrosine protein kinase", "receptor tyrosine protein kinase tyk2", "tyrosine protein kinase tyk2 and", "protein kinase tyk2 and tyrosine", "kinase tyk2 and tyrosine protein", "tyk2 and tyrosine protein kinase", "and tyrosine protein kinase jak2.", "tyrosine protein kinase jak2. these", "protein kinase jak2. these activate", "kinase jak2. these activate transcription", "jak2. these activate transcription factor", "these activate transcription factor proteins", "activate transcription factor proteins in", "transcription factor proteins in the", "factor proteins in the signal", "proteins in the signal transducer", "in the signal transducer and", "the signal transducer and activator", "signal transducer and activator of", "transducer and activator of transcription", "activator of transcription stat", "transcription stat family", "stat family particularly" ] }, { "record_id": "GLY_000594_1_1193", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020933", "r hsa", "hsa 9020933", "r hsa 9020933" ] }, { "record_id": "GLY_000594_1_1193", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 23", "23 signaling", "interleukin 23 signaling", "is a", "a heterodimer", "heterodimer of", "interleukin 12", "12 subunit", "subunit beta", "il 12p40", "which is", "is shared", "shared with", "with il12", "and interleukin", "23 subunit", "subunit alpha", "alpha il23a", "il 23p19", "subunit. the", "the functional", "functional receptor", "receptor for", "for il23", "il23 consists", "consists of", "of interleukin", "12 receptor", "receptor subunit", "beta 1", "with the", "the il12", "il12 receptor", "23 receptor", "il23r .", ". il23r", "il23r is", "is mainly", "mainly expresed", "expresed on", "on activated", "activated memory", "memory t", "t cells", "natural killer", "killer cells", "monocytes/macrophage and", "and at", "at low", "low levels", "levels on", "on dendritic", "dendritic cells", "dcs .", ". il23", "il23 is", "mainly secreted", "secreted by", "by activated", "activated macrophages", "macrophages and", "and dcs", "dcs in", "in peripheral", "peripheral tissues", "tissues such", "such as", "as skin", "intestinal mucosa", "mucosa and", "and lung.", "lung. il23", "is proinlflammatory", "proinlflammatory and", "and implicated", "implicated in", "in several", "several autoimmune", "autoimmune inflammatory", "inflammatory disorders", "disorders such", "as colitis", "psoriasis and", "and arthritis.", "arthritis. it", "it is", "is similar", "similar to", "to il", "il 12", "12 both", "both in", "in structure", "structure and", "and its", "its ability", "ability to", "cells to", "to increase", "increase interferon", "interferon \u03b3", "ifn \u03b3", "production and", "and proliferation", "the ability", "ability of", "of il", "il 23", "23 to", "to induce", "induce il", "il 17.", "17. il23", "il23 activates", "activates the", "the janus", "janus kinases", "kinases jak2", "jak2 and", "and tyk2", "resulting in", "in phosphorylation", "phosphorylation of", "of the", "the receptor", "receptor complex", "which forms", "forms the", "the docking", "docking sites", "sites for", "for signal", "signal transducer", "transducer and", "and activator", "activator of", "of transcription", "transcription 3", "and stat4", "stat4 to", "to bind", "bind and", "and become", "become phosphorylated.", "23 il23", "is a heterodimer", "a heterodimer of", "interleukin 12 subunit", "12 subunit beta", "beta il12b", "il12b il", "which is shared", "is shared with", "shared with il12", "il12 and", "and interleukin 23", "interleukin 23 subunit", "23 subunit alpha", "subunit alpha il23a", "il23a il", "23p19 subunit.", "subunit. the functional", "the functional receptor", "functional receptor for", "receptor for il23", "for il23 consists", "il23 consists of", "consists of interleukin", "of interleukin 12", "interleukin 12 receptor", "12 receptor subunit", "receptor subunit beta", "subunit beta 1", "1 il12rb1", "shared with the", "with the il12", "the il12 receptor", "receptor and", "interleukin 23 receptor", "receptor il23r", "il23r . il23r", ". il23r is", "il23r is mainly", "is mainly expresed", "mainly expresed on", "expresed on activated", "on activated memory", "activated memory t", "memory t cells", "cells natural", "natural killer cells", "cells monocytes/macrophage", "monocytes/macrophage and at", "and at low", "at low levels", "low levels on", "levels on dendritic", "on dendritic cells", "cells dcs", "dcs . il23", ". il23 is", "il23 is mainly", "is mainly secreted", "mainly secreted by", "secreted by activated", "by activated macrophages", "activated macrophages and", "macrophages and dcs", "and dcs in", "dcs in peripheral", "in peripheral tissues", "peripheral tissues such", "tissues such as", "such as skin", "skin intestinal", "intestinal mucosa and", "mucosa and lung.", "and lung. il23", "lung. il23 is", "il23 is proinlflammatory", "is proinlflammatory and", "proinlflammatory and implicated", "and implicated in", "implicated in several", "in several autoimmune", "several autoimmune inflammatory", "autoimmune inflammatory disorders", "inflammatory disorders such", "disorders such as", "such as colitis", "colitis gastritis", "gastritis psoriasis", "psoriasis and arthritis.", "and arthritis. it", "arthritis. it is", "it is similar", "is similar to", "similar to il", "to il 12", "il 12 both", "12 both in", "both in structure", "in structure and", "structure and its", "and its ability", "its ability to", "to memory", "t cells to", "cells to increase", "to increase interferon", "increase interferon \u03b3", "\u03b3 ifn", "\u03b3 production", "production and proliferation", "proliferation the", "the ability of", "ability of il", "of il 23", "il 23 to", "23 to induce", "to induce il", "induce il 17.", "il 17. il23", "17. il23 activates", "il23 activates the", "activates the janus", "the janus kinases", "janus kinases jak2", "kinases jak2 and", "jak2 and tyk2", "tyk2 resulting", "resulting in phosphorylation", "in phosphorylation of", "phosphorylation of the", "of the receptor", "the receptor complex", "complex which", "which forms the", "forms the docking", "the docking sites", "docking sites for", "sites for signal", "for signal transducer", "signal transducer and", "transducer and activator", "and activator of", "activator of transcription", "of transcription 3", "3 stat3", "stat3 and", "and stat4 to", "stat4 to bind", "to bind and", "bind and become", "and become phosphorylated.", "interleukin 23 il23", "il23 is a", "is a heterodimer of", "heterodimer of interleukin", "interleukin 12 subunit beta", "subunit beta il12b", "il12b il 12p40", "12p40 which", "which is shared with", "is shared with il12", "with il12 and", "il12 and interleukin", "and interleukin 23 subunit", "interleukin 23 subunit alpha", "23 subunit alpha il23a", "alpha il23a il", "il23a il 23p19", "il 23p19 subunit.", "23p19 subunit. the", "subunit. the functional receptor", "the functional receptor for", "functional receptor for il23", "receptor for il23 consists", "for il23 consists of", "il23 consists of interleukin", "consists of interleukin 12", "of interleukin 12 receptor", "interleukin 12 receptor subunit", "12 receptor subunit beta", "receptor subunit beta 1", "beta 1 il12rb1", "il12rb1 which", "is shared with the", "shared with the il12", "with the il12 receptor", "il12 receptor and", "receptor and interleukin", "and interleukin 23 receptor", "23 receptor il23r", "receptor il23r .", "il23r . il23r is", ". il23r is mainly", "il23r is mainly expresed", "is mainly expresed on", "mainly expresed on activated", "expresed on activated memory", "on activated memory t", "activated memory t cells", "t cells natural", "cells natural killer", "killer cells monocytes/macrophage", "cells monocytes/macrophage and", "monocytes/macrophage and at low", "and at low levels", "at low levels on", "low levels on dendritic", "levels on dendritic cells", "dendritic cells dcs", "cells dcs .", "dcs . il23 is", ". il23 is mainly", "il23 is mainly secreted", "is mainly secreted by", "mainly secreted by activated", "secreted by activated macrophages", "by activated macrophages and", "activated macrophages and dcs", "macrophages and dcs in", "and dcs in peripheral", "dcs in peripheral tissues", "in peripheral tissues such", "peripheral tissues such as", "tissues such as skin", "as skin intestinal", "skin intestinal mucosa", "intestinal mucosa and lung.", "mucosa and lung. il23", "and lung. il23 is", "lung. il23 is proinlflammatory", "il23 is proinlflammatory and", "is proinlflammatory and implicated", "proinlflammatory and implicated in", "and implicated in several", "implicated in several autoimmune", "in several autoimmune inflammatory", "several autoimmune inflammatory disorders", "autoimmune inflammatory disorders such", "inflammatory disorders such as", "disorders such as colitis", "as colitis gastritis", "gastritis psoriasis and", "psoriasis and arthritis. it", "and arthritis. it is", "arthritis. it is similar", "it is similar to", "is similar to il", "similar to il 12", "to il 12 both", "il 12 both in", "12 both in structure", "both in structure and", "in structure and its", "structure and its ability", "and its ability to", "ability to memory", "to memory t", "memory t cells to", "t cells to increase", "cells to increase interferon", "to increase interferon \u03b3", "interferon \u03b3 ifn", "\u03b3 ifn \u03b3", "ifn \u03b3 production", "\u03b3 production and", "and proliferation the", "proliferation the ability", "the ability of il", "ability of il 23", "of il 23 to", "il 23 to induce", "23 to induce il", "to induce il 17.", "induce il 17. il23", "il 17. il23 activates", "17. il23 activates the", "il23 activates the janus", "activates the janus kinases", "the janus kinases jak2", "janus kinases jak2 and", "kinases jak2 and tyk2", "and tyk2 resulting", "tyk2 resulting in", "resulting in phosphorylation of", "in phosphorylation of the", "phosphorylation of the receptor", "of the receptor complex", "receptor complex which", "complex which forms", "which forms the docking", "forms the docking sites", "the docking sites for", "docking sites for signal", "sites for signal transducer", "for signal transducer and", "signal transducer and activator", "transducer and activator of", "and activator of transcription", "activator of transcription 3", "transcription 3 stat3", "stat3 and stat4", "and stat4 to bind", "stat4 to bind and", "to bind and become", "bind and become phosphorylated.", "23 il23 is", "il23 is a heterodimer", "a heterodimer of interleukin", "heterodimer of interleukin 12", "of interleukin 12 subunit", "12 subunit beta il12b", "beta il12b il", "il 12p40 which", "12p40 which is", "which is shared with il12", "shared with il12 and", "with il12 and interleukin", "il12 and interleukin 23", "and interleukin 23 subunit alpha", "interleukin 23 subunit alpha il23a", "subunit alpha il23a il", "alpha il23a il 23p19", "il 23p19 subunit. the", "23p19 subunit. the functional", "subunit. the functional receptor for", "the functional receptor for il23", "functional receptor for il23 consists", "receptor for il23 consists of", "for il23 consists of interleukin", "il23 consists of interleukin 12", "consists of interleukin 12 receptor", "of interleukin 12 receptor subunit", "interleukin 12 receptor subunit beta", "12 receptor subunit beta 1", "subunit beta 1 il12rb1", "il12rb1 which is", "which is shared with the", "is shared with the il12", "shared with the il12 receptor", "the il12 receptor and", "il12 receptor and interleukin", "receptor and interleukin 23", "interleukin 23 receptor il23r", "23 receptor il23r .", "receptor il23r . il23r", "il23r . il23r is mainly", ". il23r is mainly expresed", "il23r is mainly expresed on", "is mainly expresed on activated", "mainly expresed on activated memory", "expresed on activated memory t", "on activated memory t cells", "memory t cells natural", "t cells natural killer", "cells natural killer cells", "natural killer cells monocytes/macrophage", "killer cells monocytes/macrophage and", "cells monocytes/macrophage and at", "monocytes/macrophage and at low levels", "and at low levels on", "at low levels on dendritic", "low levels on dendritic cells", "on dendritic cells dcs", "dendritic cells dcs .", "cells dcs . il23", "dcs . il23 is mainly", ". il23 is mainly secreted", "il23 is mainly secreted by", "is mainly secreted by activated", "mainly secreted by activated macrophages", "secreted by activated macrophages and", "by activated macrophages and dcs", "activated macrophages and dcs in", "macrophages and dcs in peripheral", "and dcs in peripheral tissues", "dcs in peripheral tissues such", "in peripheral tissues such as", "peripheral tissues such as skin", "such as skin intestinal", "as skin intestinal mucosa", "skin intestinal mucosa and", "intestinal mucosa and lung. il23", "mucosa and lung. il23 is", "and lung. il23 is proinlflammatory", "lung. il23 is proinlflammatory and", "il23 is proinlflammatory and implicated", "is proinlflammatory and implicated in", "proinlflammatory and implicated in several", "and implicated in several autoimmune", "implicated in several autoimmune inflammatory", "in several autoimmune inflammatory disorders", "several autoimmune inflammatory disorders such", "autoimmune inflammatory disorders such as", "inflammatory disorders such as colitis", "such as colitis gastritis", "colitis gastritis psoriasis", "gastritis psoriasis and arthritis.", "psoriasis and arthritis. it is", "and arthritis. it is similar", "arthritis. it is similar to", "it is similar to il", "is similar to il 12", "similar to il 12 both", "to il 12 both in", "il 12 both in structure", "12 both in structure and", "both in structure and its", "in structure and its ability", "structure and its ability to", "its ability to memory", "ability to memory t", "to memory t cells", "memory t cells to increase", "t cells to increase interferon", "cells to increase interferon \u03b3", "increase interferon \u03b3 ifn", "interferon \u03b3 ifn \u03b3", "ifn \u03b3 production and", "\u03b3 production and proliferation", "production and proliferation the", "and proliferation the ability", "proliferation the ability of", "the ability of il 23", "ability of il 23 to", "of il 23 to induce", "il 23 to induce il", "23 to induce il 17.", "to induce il 17. il23", "induce il 17. il23 activates", "il 17. il23 activates the", "17. il23 activates the janus", "il23 activates the janus kinases", "activates the janus kinases jak2", "the janus kinases jak2 and", "janus kinases jak2 and tyk2", "jak2 and tyk2 resulting", "and tyk2 resulting in", "tyk2 resulting in phosphorylation", "resulting in phosphorylation of the", "in phosphorylation of the receptor", "phosphorylation of the receptor complex", "the receptor complex which", "receptor complex which forms", "complex which forms the", "which forms the docking sites", "forms the docking sites for", "the docking sites for signal", "docking sites for signal transducer", "sites for signal transducer and", "for signal transducer and activator", "signal transducer and activator of", "transducer and activator of transcription", "and activator of transcription 3", "of transcription 3 stat3", "3 stat3 and", "stat3 and stat4 to", "and stat4 to bind and", "stat4 to bind and become", "to bind and become phosphorylated." ] }, { "record_id": "GLY_000594_1_1194", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020956", "r hsa", "hsa 9020956", "r hsa 9020956" ] }, { "record_id": "GLY_000594_1_1194", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 27", "27 signaling", "interleukin 27 signaling", "is a", "a heterodimeric", "heterodimeric cytokine", "cytokine that", "that contains", "contains epstein", "epstein barr", "barr virus\u2013induced", "virus\u2013induced gene", "gene 3", "and il27p28", "il27 .", ". it", "it signals", "signals through", "through a", "a receptor", "receptor composed", "composed of", "of interleukin", "interleukin 6", "6 receptor", "receptor subunit", "subunit beta", "which is", "is utilized", "utilized by", "by many", "many cytokines", "and interleukin", "27 receptor", "subunit alpha", "wsx 1", "yoshida &", "& hunter", "hunter 2015", "2015 .", "27 il27", "il27 is", "is a heterodimeric", "a heterodimeric cytokine", "heterodimeric cytokine that", "cytokine that contains", "that contains epstein", "contains epstein barr", "epstein barr virus\u2013induced", "barr virus\u2013induced gene", "virus\u2013induced gene 3", "3 ebi3", "ebi3 and", "il27p28 il27", "il27 . it", ". it signals", "it signals through", "signals 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epinephrine", "adrenaline epinephrine and", "epinephrine and inhibited by", "and inhibited by insulin. both", "inhibited by insulin. both isoforms", "by insulin. both isoforms of", "insulin. both isoforms of liver", "both isoforms of liver x", "isoforms of liver x receptor", "liver x receptor lxr\u03b1", "receptor lxr\u03b1 nr1h3", "lxr\u03b1 nr1h3 and", "nr1h2 are expressed", "are expressed in mature mouse", "expressed in mature mouse and", "in mature mouse and human", "mature mouse and human adipocytes", "and human adipocytes juvet", "human adipocytes juvet lk", "adipocytes juvet lk et", "juvet lk et al. 2003", "lk et al. 2003 .", "et al. 2003 . expression", "al. 2003 . expression of", "2003 . expression of nr1h3", ". expression of nr1h3 is", "expression of nr1h3 is up", "of nr1h3 is up regulated", "nr1h3 is up regulated during", "is up regulated during adipocyte", "up regulated during adipocyte differentiation", "during adipocyte differentiation juvet", "adipocyte differentiation 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primary adipocytes", "human primary adipocytes lxr", "primary adipocytes lxr activation", "adipocytes lxr activation led", "lxr activation led to an", "activation led to an increase", "led to an increase in", "to an increase in basal", "increase in basal but", "in basal but not", "basal but not hormone", "not hormone stimulated lipolysis", "hormone stimulated lipolysis as", "stimulated lipolysis as measured", "lipolysis as measured by glycerol", "as measured by glycerol release", "by glycerol release ross", "glycerol release ross se", "release ross se et", "et al. 2002 stenson", "al. 2002 stenson bm", "2002 stenson bm et", "bm et al. 2011 .", "et al. 2011 . another", "al. 2011 . another study", "2011 . another study showed", ". another study showed that", "another study showed that administration", "study showed that administration of", "showed that administration of synthetic", "that administration of synthetic ligands", "administration of synthetic ligands of", "of synthetic ligands of nr1h2/", "synthetic ligands of nr1h2/ nr1h3", "of nr1h2/ nr1h3 t0901317", "nr1h2/ nr1h3 t0901317 or", "nr1h3 t0901317 or gw3965", "t0901317 or gw3965 to", "or gw3965 to mice", "gw3965 to mice resulted", "to mice resulted in smaller", "mice resulted in smaller adipocytes", "resulted in smaller adipocytes and", "in smaller adipocytes and increased", "smaller adipocytes and increased serum", "adipocytes and increased serum free", "and increased serum free fatty", "increased serum free fatty acid", "serum free fatty acid and", "free fatty acid and glycerol", "fatty acid and glycerol concentrations", "and glycerol concentrations suggesting", "glycerol concentrations suggesting increased", "concentrations suggesting increased adipocyte", "increased adipocyte lipolysis commerford", "adipocyte lipolysis commerford sr", "lipolysis commerford sr et", "commerford sr et al. 2007", "sr et al. 2007 .", "et al. 2007 . further", "2007 . further microarray", ". further microarray analysis", "further microarray analysis of", "microarray analysis of human adipocytes", "analysis of human adipocytes following", "of human adipocytes following nr1h3", "human adipocytes following nr1h3 or", "adipocytes following nr1h3 or nr1h2", "following nr1h3 or nr1h2 activation", "nr1h3 or nr1h2 activation revealed", "or nr1h2 activation revealed altered", "nr1h2 activation revealed altered gene", "activation revealed altered gene expression", "revealed altered gene expression of", "altered gene expression of several", "gene expression of several lipolysis", "expression of several lipolysis regulating", "of several lipolysis regulating proteins", "several lipolysis regulating proteins such", "lipolysis regulating proteins such as", "regulating proteins such as perilipin1", "such as perilipin1 plin1", "plin1 which was", "which was also confirmed by", "was also confirmed by quantitative", "also confirmed by quantitative real", "confirmed by quantitative real time", "by quantitative real time pcr", "real time pcr stenson", "time pcr stenson bm", "pcr stenson bm et", "et al. 2011 . selective", "al. 2011 . selective knockdown", "2011 . selective knockdown of", ". selective knockdown of either", "selective knockdown of either nr1h2", "knockdown of either nr1h2 or", "of either nr1h2 or nr1h3", "either nr1h2 or nr1h3 showed", "nr1h2 or nr1h3 showed that", "or nr1h3 showed that nr1h3", "showed that nr1h3 lxr\u03b1", "nr1h3 lxr\u03b1 was", "lxr\u03b1 was the major", "was the major isoform mediating", "the major isoform mediating the", "major isoform mediating the lipolysis", "isoform mediating the lipolysis related", "mediating the lipolysis related effects", "the lipolysis related effects of", "lipolysis related effects of lxr", "related effects of lxr agonists", "of lxr agonists stenson", "lxr agonists stenson bm", "agonists stenson bm et", "et al. 2011 . in", "al. 2011 . in addition", ". in addition the", "in addition the absence", "addition the absence of", "absence of nr1h3 lxr\u03b1", "nr1h3 lxr\u03b1 in", "lxr\u03b1 in mouse adipose", "in mouse adipose tissue resulted", "mouse adipose tissue resulted in", "adipose tissue resulted in elevated", "tissue resulted in elevated adiposity", "resulted in elevated adiposity through", "in elevated adiposity through a", "elevated adiposity through a decrease", "adiposity through a decrease of", "through a decrease of both", "a decrease of both lipolytic", "decrease of both lipolytic and", "of both lipolytic and oxidative", "both lipolytic and oxidative capacities", "lipolytic and oxidative capacities in", "and oxidative capacities in white", "oxidative capacities in white adipose", "capacities in white adipose tissue", "white adipose tissue dib", "adipose tissue dib l", "tissue dib l et", "dib l et al. 2014", "l et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1201", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9034864", "r hsa", "hsa 9034864", "r hsa 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"not bind avpr2", "bind avpr2 and", "avpr2 and causes", "and causes neurohypophyseal", "causes neurohypophyseal diabetes", "neurohypophyseal diabetes insipidus", "insipidus ndi", "defective avp does not", "avp does not bind", "does not bind avpr2", "not bind avpr2 and", "bind avpr2 and causes", "avpr2 and causes neurohypophyseal", "and causes neurohypophyseal diabetes", "causes neurohypophyseal diabetes insipidus", "diabetes insipidus ndi", "defective avp does not bind", "avp does not bind avpr2", "does not bind avpr2 and", "not bind avpr2 and causes", "bind avpr2 and causes neurohypophyseal", "avpr2 and causes neurohypophyseal diabetes", "and causes neurohypophyseal diabetes insipidus", "neurohypophyseal diabetes insipidus ndi", "arginine vasopressin", "avp 20", "20 28", "is a", "a 9", "9 amino", "amino acid", "acid long", "long signal", "signal peptide", "peptide produced", "produced by", "by cleavage", "cleavage of", "of the", "the precursor", "precursor protein", "protein avp", 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              mutations", "decreased.

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              mutations", "are decreased.

              mutations in", "decreased.

              mutations in avp", "in avp make", "avp make it", "make it unavailable", "it unavailable to", "unavailable to its", "to its avprs", "its avprs in", "avprs in the", "kidney resulting", "resulting in dysregulation", "in dysregulation of", "dysregulation of water", "of water reabsorption.", "water reabsorption. this", "reabsorption. this can", "this can cause", "can cause familial", "cause familial neurohypophyseal", "familial neurohypophyseal diabetes", "insipidus fndi", "an autosomal dominant", "autosomal dominant disorder", "dominant disorder characterised", "disorder characterised by", "characterised by persistent", "by persistent excessive", "persistent excessive thirst", "excessive thirst resulting", "thirst resulting in", "resulting in constant", "in constant drinking", "drinking polydipsia", "polydipsia and", "and passage of", "passage of large", "of large volumes", "large volumes of", "volumes of urine", "urine polyuria", "polyuria . in", ". in fndi", "fndi the", "the production and", "production and release", "and release of", "release of avp", "of avp from", "avp from the", "from the posterior", "the posterior pituitary", "posterior pituitary gland", "pituitary gland is", "gland is impaired", "impaired moeller", "moeller et al.", "et al. 2013", "al. 2013 .", "arginine vasopressin avp", "vasopressin avp 20", "28 is", "is a 9 amino", "a 9 amino acid", "9 amino acid long", "amino acid long signal", "acid long signal peptide", "long signal peptide produced", "signal peptide produced by", "peptide produced by cleavage", "produced by cleavage of", "by cleavage of the", "cleavage of the precursor", "of the precursor protein", "the precursor protein avp", "precursor protein avp in", "protein avp in the", "avp in the hypothalamus.", "in the hypothalamus. it", "the hypothalamus. it mediates", "hypothalamus. it mediates the", "it mediates the reabsorption", "mediates the reabsorption of", "the reabsorption of water", "reabsorption of water in", "of water in the", "water in the kidney", "in the kidney and", "the kidney and its", "kidney and its synthesis", "and its synthesis and", "its synthesis and release", "synthesis and release are", "and release are physiologically", "release are physiologically regulated", "are physiologically regulated by", "physiologically regulated by plasma", "regulated by plasma osmolarity", "plasma osmolarity blood", "osmolarity blood pressure", "blood pressure and/or blood", "pressure and/or blood volume.", "and/or blood volume. avp", "blood volume. avp 20", "volume. avp 20 28", "20 28 binds", "28 binds to", "binds to vasopressin receptors", "to vasopressin receptors avpr1", "vasopressin receptors avpr1 and", "receptors avpr1 and 2", "and 2 located", "2 located on", "located on the basolateral", "on the basolateral surface", "the basolateral surface of", "basolateral surface of the", "surface of the kidney", "of the kidney collecting", "the kidney collecting duct.", "kidney collecting duct. this", "collecting duct. this binding", "duct. this binding results", "this binding results in", "binding results in interaction", "results in interaction of", "in interaction of avprs", "interaction of avprs with", "of avprs with the", "avprs with the g", "with the g protein", "the g protein alpha", "g protein alpha s.", "protein alpha s. following", "alpha s. following a", "s. following a cascade", "following a cascade of", "a cascade of downstream", "cascade of downstream events", "downstream events ultimately", "events ultimately the", "ultimately the water channel", "the water channel aquaporin", "water channel aquaporin 2", "aquaporin 2 aqp2", "aqp2 translocates from", "translocates from intracellular stores", "from intracellular stores to", "intracellular stores to the", "stores to the apical", "to the apical surface", "the apical surface where", "apical surface where it", "surface where it functions", "where it functions as", "it functions as the", "functions as the entry", "as the entry site", "the entry site for", "entry site for water", "site for water reabsorption.", "for water reabsorption. when", "water reabsorption. when water", "reabsorption. when water balance", "when water balance is", "water balance is achieved", "is achieved plasma", "achieved plasma levels", "plasma levels of avp", "levels of avp 20", "of avp 20 28", "20 28 drop", "28 drop and", "drop and aqp2 levels", "and aqp2 levels in", "aqp2 levels in the", "levels in the apical", "in the apical plasma", "the apical plasma membrane", "apical plasma membrane are", "plasma membrane are decreased.

              mutations", "membrane are decreased.

              mutations in", "are decreased.

              mutations in avp", "decreased.

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constant", "resulting in constant drinking", "constant drinking polydipsia", "polydipsia and passage", "and passage of large", "passage of large volumes", "of large volumes of", "large volumes of urine", "of urine polyuria", "urine polyuria .", "polyuria . in fndi", "in fndi the", "fndi the production", "the production and release", "production and release of", "and release of avp", "release of avp from", "of avp from the", "avp from the posterior", "from the posterior pituitary", "the posterior pituitary gland", "posterior pituitary gland is", "pituitary gland is impaired", "is impaired moeller", "impaired moeller et", "moeller et al. 2013", "et al. 2013 .", "arginine vasopressin avp 20", "vasopressin avp 20 28", "20 28 is", "28 is a", "is a 9 amino acid", "a 9 amino acid long", "9 amino acid long signal", "amino acid long signal peptide", "acid long signal peptide produced", "long signal peptide produced by", "signal peptide produced by cleavage", "peptide produced by cleavage of", "produced by cleavage of the", "by cleavage of the precursor", "cleavage of the precursor protein", "of the precursor protein avp", "the precursor protein avp in", "precursor protein avp in the", "protein avp in the hypothalamus.", "avp in the hypothalamus. it", "in the hypothalamus. it mediates", "the hypothalamus. it mediates the", "hypothalamus. it mediates the reabsorption", "it mediates the reabsorption of", "mediates the reabsorption of water", "the reabsorption of water in", "reabsorption of water in the", "of water in the kidney", "water in the kidney and", "in the kidney and its", "the kidney and its synthesis", "kidney and its synthesis and", "and its synthesis and release", "its synthesis and release are", "synthesis and release are physiologically", "and release are physiologically regulated", "release are physiologically regulated by", "are physiologically regulated by plasma", "physiologically regulated by plasma osmolarity", "by plasma osmolarity blood", "plasma osmolarity blood pressure", "osmolarity blood pressure and/or", "blood pressure and/or blood volume.", "pressure and/or blood volume. avp", "and/or blood volume. avp 20", "blood volume. avp 20 28", "avp 20 28 binds", "20 28 binds to", "28 binds to vasopressin", "binds to vasopressin receptors avpr1", "to vasopressin receptors avpr1 and", "vasopressin receptors avpr1 and 2", "avpr1 and 2 located", "and 2 located on", "2 located on the", "located on the basolateral surface", "on the basolateral surface of", "the basolateral surface of the", "basolateral surface of the kidney", "surface of the kidney collecting", "of the kidney collecting duct.", "the kidney collecting duct. this", "kidney collecting duct. this binding", "collecting duct. this binding results", "duct. this binding results in", "this binding results in interaction", "binding results in interaction of", "results in interaction of avprs", "in interaction of avprs with", "interaction of avprs with the", "of avprs with the g", "avprs with the g protein", "with the g protein alpha", "the g protein alpha s.", "g protein alpha s. following", "protein alpha s. following a", "alpha s. following a cascade", "s. following a cascade of", "following a cascade of downstream", "a cascade of downstream events", "of downstream events ultimately", "downstream events ultimately the", "events ultimately the water", "ultimately the water channel aquaporin", "the water channel aquaporin 2", "channel aquaporin 2 aqp2", "2 aqp2 translocates", "aqp2 translocates from intracellular", "translocates from intracellular stores to", "from intracellular stores to the", "intracellular stores to the apical", "stores to the apical surface", "to the apical surface where", "the apical surface where it", "apical surface where it functions", "surface where it functions as", "where it functions as the", "it functions as the entry", "functions as the entry site", "as the entry site for", "the entry site for water", "entry site for water 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              mutations", "plasma membrane are decreased.

              mutations in", "membrane are decreased.

              mutations in avp", "are decreased.

              mutations in avp make", "decreased.

              mutations in avp make it", "in avp make it unavailable", "avp make it unavailable to", "make it unavailable to its", "it unavailable to its avprs", "unavailable to its avprs in", "to its avprs in the", "its avprs in the kidney", "in the kidney resulting", "the kidney resulting in", "kidney resulting in dysregulation", "resulting in dysregulation of water", "in dysregulation of water reabsorption.", "dysregulation of water reabsorption. this", "of water reabsorption. this can", "water reabsorption. this can cause", "reabsorption. this can cause familial", "this can cause familial neurohypophyseal", "can cause familial neurohypophyseal diabetes", "cause familial neurohypophyseal diabetes insipidus", "neurohypophyseal diabetes insipidus fndi", "fndi an autosomal", "an autosomal dominant disorder characterised", "autosomal dominant disorder characterised by", "dominant disorder characterised by persistent", "disorder characterised by persistent excessive", "characterised by persistent excessive thirst", "by persistent excessive thirst resulting", "persistent excessive thirst resulting in", "excessive thirst resulting in constant", "thirst resulting in constant drinking", "in constant drinking polydipsia", "drinking polydipsia and", "polydipsia and passage of", "and passage of large volumes", "passage of large volumes of", "of large volumes of urine", "volumes of urine polyuria", "of urine polyuria .", "urine polyuria . in", ". in fndi the", "in fndi the production", "fndi the production and", "the production and release of", "production and release of avp", "and release of avp from", "release of avp from the", "of avp from the posterior", "avp from the posterior pituitary", "from the posterior pituitary gland", "the posterior pituitary gland is", "posterior pituitary gland is impaired", "gland is impaired moeller", "is impaired moeller et", "impaired moeller et al.", "moeller et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1203", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9037629", "r hsa", "hsa 9037629", "r hsa 9037629" ] }, { "record_id": "GLY_000594_1_1203", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lewis blood", "blood group", "group biosynthesis", "lewis blood group", "blood group biosynthesis", "lewis blood group biosynthesis", "the lewis", "lewis antigen", "antigen system", "system is", "is a", "a human", "human blood", "group system", "system based", "based upon", "upon genes", "genes on", "on chromosome", "chromosome 19", "19 p13.3", "the fut3", "fut3 gene", "gene aka", "aka the", "the le", "le gene", "and 19q13.3", "fut2 gene", "the se", "se gene", "gene .", ". both", "both genes", "genes are", "are expressed", "expressed in", "in glandular", "glandular epithelia", "epithelia and", "and have", "have dominant", "dominant alleles", "le and", "and se", "coding for", "for enzymes", "enzymes with", "with fucosyltransferase", "fucosyltransferase activity", "activity and", "and recessive", "recessive alleles", "that are", "are non", "non functional.", "functional. there", "there are", "are two", "two main", "main lewis", "lewis antigens", "lewis a", "a and", "and lewis", "lewis b", "b which", "which can", "can result", "result in", "in three", "three common", "common phenotypes:", "phenotypes: le", "le a+b", "le a", "a b+", "and le", "a b", ". lewis", "antigens are", "are components", "components of", "of exocrine", "exocrine epithelial", "epithelial secretions", "and can", "can be", "be adsorbed", "adsorbed onto", "onto the", "the surfaces", "surfaces of", "of red", "red blood", "blood cells", "therefore are", "are not", "not produced", "produced directly", "directly by", "by rbcs", "rbcs themselves", "ewald &", "& sumner", "sumner 2016", "2016 .

              the", ".

              the same", "same two", "two oligosaccharides", "type 1", "1 and", "and type", "type 2", "used to", "to determine", "determine abo", "abo blood", "blood types", "types are", "are also", "also utilised", "utilised by", "by the", "lewis system.", "system. fucosyltransferase", "fucosyltransferase 3", "adds fucose", "fucose to", "to type", "1 chains", "chains to", "to form", "form the", "a antigen", "lea .", ". if", "if the", "the individual", "individual is", "a non", "non secretor", "lacks the", "the se", "se gene", "homozygous sese", "lea is", "is adsorbed", "the red", "red cell", "and that", "that individual", "is lea", "lea type.", "type. approximately", "approximately 80%", "80% of", "of the", "the population", "population has", "has the", "se gene.", "gene. functional", "functional fucosyltransferase", "fucosyltransferase 2", "adds a", "a fucose", "to lea", "lea to", "form leb.", "leb. both", "both lea", "lea and", "and leb", "leb present", "present in", "in the", "the plasma", "plasma of", "of secretors", "secretors but", "but lea", "lea preferentially", "preferentially adsorbs", "adsorbs onto", "the rbc", "rbc and", "and therefore", "individual types", "types as", "as leb.", "leb. other", "other futs", "especially fut4", "can add", "add a", "2 chains", "lewis x", "x antigen", "lex .", ". further", "further fucosylation", "fucosylation of", "of lex", "lex by", "by fut2", "fut2 produces", "produces the", "lewis y", "y antigen", "ley .", "lex and", "and ley", "ley are", "are structural", "structural isomers", "isomers of", "of lea", "and leb.", "leb. the", "the formation", "formation of", "of ley", "ley is", "is controlled", "controlled by", "by se/se", "se/se as", "as in", "the case", "case for", "for leb.", "leb. lea", "and lex", "lex antigens", "antigens can", "can also", "also undergo", "undergo sialation", "sialation to", "to produce", "produce sialated", "sialated forms", "forms of", "of these", "these antigens.

              aberrant", "antigens.

              aberrant glycosylation", "glycosylation of", "of tumour", "tumour cells", "cells is", "is recognised", "recognised as", "as a", "a feature", "feature of", "of cancer", "cancer pathogenesis.", "pathogenesis. overexpression", "overexpression of", "of fucosylated", "fucosylated and", "and sialated", "sialated lewis", "antigens frequently", "frequently occurs", "occurs on", "on the", "cancer cells", "cells and", "and is", "is mainly", "mainly attributed", "attributed to", "to upregulated", "upregulated expression", "expression of", "the relevant", "relevant fucosyltransferases", "futs .", "the sialyl", "sialyl lewis", "also known", "known as", "as the", "the ca19", "ca19 9", "9 antigen", "is the", "the most", "most common", "common tumour", "tumour marker", "marker used", "used primarily", "primarily in", "the management", "management of", "of pancreatic", "pancreatic and", "and gastrointestinal", "gastrointestinal cancers", "cancers worldwide", "magnani 2004", "blanas et", "et al.", "al. 2018", "2018 .

              selectins", "and p", "p selectin", "are type", "type i", "i membrane", "membrane proteins", "proteins composed", "composed of", "of long", "long n", "n terminus", "terminus c", "c type", "type lectin", "lectin domains", "domains protruding", "protruding into", "into the", "the extracellular", "extracellular space", "space and", "and with", "with a", "a short", "short cytoplasmic", "cytoplasmic tail.", "tail. they", "they bind", "bind carbohydrate", "carbohydrate structures", "structures through", "through a", "a ca2+", "ca2+ dependent", "dependent domain", "the minimal", "minimal sugar", "sugar structure", "structure recognised", "recognised fulfilled", "fulfilled by", "by slea", "slea and", "and slex.", "slex. selectins", "selectins are", "are found", "found on", "on endothelial", "endothelial cells", "platelets and", "and leukocytes", "leukocytes and", "and are", "are involved", "involved in", "in trafficking", "trafficking of", "of cells", "cells of", "the innate", "innate immune", "immune system", "t lymphocytes", "lymphocytes and", "and platelets", "thereby playing", "playing important", "important roles", "roles in", "in chronic", "chronic and", "and acute", "acute inflammation", "inflammation and", "and haemostasis.", "haemostasis. selectins", "selectins also", "also play", "play a", "a role", "role in", "in cancer", "cancer progression.", "progression. metastasis", "metastasis is", "is facilitated", "facilitated by", "by cell", "cell cell", "cell interactions", "interactions between", "between cancer", "and endothelial", "cells in", "in distant", "distant tissues.", "tissues. in", "in addition", "cancer cell", "interactions with", "with platelets", "leukocytes contribute", "contribute to", "to cancer", "cell adhesion", "and the", "the establishment", "establishment of", "of metastatic", "metastatic lesions.", "lesions. targeting", "targeting selectins", "selectins and", "and their", "their ligands", "ligands as", "as well", "well as", "the enzymes", "enzymes involved", "in their", "their generation", "in particular", "particular sialyl", "sialyl transferases", "could be", "be a", "a useful", "useful strategy", "strategy in", "cancer treatment", "ley 2003", "laubli &", "& borsig", "borsig 2010", "cheung et", "al. 2011", "natoli et", "al. 2016", "trinchera et", "al. 2017", "2017 .", "the lewis antigen", "lewis antigen system", "antigen system is", "system is a", "is a human", "a human blood", "human blood group", "blood group system", "group system based", "system based upon", "based upon genes", "upon genes on", "genes on chromosome", "on chromosome 19", "chromosome 19 p13.3", "p13.3 the", "the fut3 gene", "fut3 gene aka", "gene aka the", "aka the le", "the le gene", "gene and", "fut2 gene aka", "aka the se", "the se gene", "se gene .", "gene . both", ". both genes", "both genes are", "genes are expressed", "are expressed in", "expressed in glandular", "in glandular epithelia", "glandular epithelia and", "epithelia and have", "and have dominant", "have dominant alleles", "alleles le", "le and se", "se respectively", "respectively coding", "coding for enzymes", "for enzymes with", "enzymes with fucosyltransferase", "with fucosyltransferase activity", "fucosyltransferase activity and", "activity and recessive", "and recessive alleles", "respectively that", "that are non", "are non functional.", "non functional. there", "functional. there are", "there are two", "are two main", "two main lewis", "main lewis antigens", "antigens lewis", "lewis a and", "a and lewis", "and lewis b", "lewis b which", "b which can", "which can result", "can result in", "result in three", "in three common", "three common phenotypes:", "common phenotypes: le", "phenotypes: le a+b", "le a b+", "b+ and", "and le a", "le a b", "b .", ". lewis antigens", "lewis antigens are", "antigens are components", "are components of", "components of exocrine", "of exocrine epithelial", "exocrine epithelial secretions", "secretions and", "and can be", "can be adsorbed", "be adsorbed onto", "adsorbed onto the", "onto the surfaces", "the surfaces of", "surfaces of red", "of red blood", "red blood cells", "cells rbcs", "therefore are not", "are not produced", "not produced directly", "produced directly by", "directly by rbcs", "by rbcs themselves", "themselves ewald", "ewald & sumner", "& sumner 2016", "sumner 2016 .

              the", "2016 .

              the same", ".

              the same two", "same two oligosaccharides", "oligosaccharides type", "type 1 and", "1 and type", "and type 2", "2 used", "used to determine", "to determine abo", "determine abo blood", "abo blood types", "blood types are", "types are also", "are also utilised", "also utilised by", "utilised by the", "by the lewis", "the lewis system.", "lewis system. fucosyltransferase", "system. fucosyltransferase 3", "3 fut3", "fut3 le", "le adds", "adds fucose to", "fucose to type", "to type 1", "type 1 chains", "1 chains to", "chains to form", "to form the", "form the lewis", "the lewis a", "lewis a antigen", "antigen lea", "lea . if", ". if the", "if the individual", "the individual is", "individual is a", "is a non", "a non secretor", "secretor lacks", "lacks the se", "the se gene", "gene homozygous", "lea is adsorbed", "is adsorbed onto", "onto the red", "the red cell", "cell and", "and that individual", "that individual is", "individual is lea", "is lea type.", "lea type. approximately", "type. approximately 80%", "approximately 80% of", "80% of the", "of the population", "the population has", "population has the", "has the se", "the se gene.", "se gene. functional", "gene. functional fucosyltransferase", "functional fucosyltransferase 2", "2 fut2", "fut2 se", "se adds", "adds a fucose", "a fucose to", "fucose to lea", "to lea to", "lea to form", "to form leb.", "form leb. both", "leb. both lea", "both lea and", "lea and leb", "and leb present", "leb present in", "present in the", "in the plasma", "the plasma of", "plasma of secretors", "of secretors but", "secretors but lea", "but lea preferentially", "lea preferentially adsorbs", "preferentially adsorbs onto", "adsorbs onto the", "onto the rbc", "the rbc and", "rbc and therefore", "therefore the", "the individual types", "individual types as", "types as leb.", "as leb. other", "leb. other futs", "futs especially", "fut4 can", "can add a", "add a fucose", "to type 2", "type 2 chains", "2 chains to", "the lewis x", "lewis x antigen", "antigen lex", "lex . further", ". further fucosylation", "further fucosylation of", "fucosylation of lex", "of lex by", "lex by fut2", "by fut2 produces", "fut2 produces the", "produces the lewis", "the lewis y", "lewis y antigen", "antigen ley", ". lex", "lex and ley", "and ley are", "ley are structural", "are structural isomers", "structural isomers of", "isomers of lea", "of lea and", "lea and leb.", "and leb. the", "leb. the formation", "the formation of", "formation of ley", "of ley is", "ley is controlled", "is controlled by", "controlled by se/se", "by se/se as", "se/se as in", "as in the", "in the case", "the case for", "case for leb.", "for leb. lea", "leb. lea and", "lea and lex", "and lex antigens", "lex antigens can", "antigens can also", "can also undergo", "also undergo sialation", "undergo sialation to", "sialation to produce", "to produce sialated", "produce sialated forms", "sialated forms of", "forms of these", "of these antigens.

              aberrant", "these antigens.

              aberrant glycosylation", "antigens.

              aberrant glycosylation of", "glycosylation of tumour", "of tumour cells", "tumour cells is", "cells is recognised", "is recognised as", "recognised as a", "as a feature", "a feature of", "feature of cancer", "of cancer pathogenesis.", "cancer pathogenesis. overexpression", "pathogenesis. overexpression of", "overexpression of fucosylated", "of fucosylated and", "fucosylated and sialated", "and sialated lewis", "sialated lewis antigens", "lewis antigens frequently", "antigens frequently occurs", "frequently occurs on", "occurs on the", "on the surfaces", "surfaces of cancer", "of cancer cells", "cancer cells and", "cells and is", "and is mainly", "is mainly attributed", "mainly attributed to", "attributed to upregulated", "to upregulated expression", "upregulated expression of", "expression of the", "of the relevant", "the relevant fucosyltransferases", "fucosyltransferases futs", ". the", "the sialyl lewis", "sialyl lewis a", "antigen slea", "also known as", "known as the", "as the ca19", "the ca19 9", "ca19 9 antigen", "antigen is", "is the most", "the most common", "most common tumour", "common tumour marker", "tumour marker used", "marker used primarily", "used primarily in", "primarily in the", "in the management", "the management of", "management of pancreatic", "of pancreatic and", "pancreatic and gastrointestinal", "and gastrointestinal cancers", "gastrointestinal cancers worldwide", "worldwide magnani", "2004 blanas", "blanas et al.", "et al. 2018", "al. 2018 .

              selectins", ".

              selectins l", "e and", "and p selectin", "selectin are", "are type i", "type i membrane", "i membrane proteins", "membrane proteins composed", "proteins composed of", "composed of long", "of long n", "long n terminus", "n terminus c", "terminus c type", "c type lectin", "type lectin domains", "lectin domains protruding", "domains protruding into", "protruding into the", "into the extracellular", "the extracellular space", "extracellular space and", "space and with", "and with a", "with a short", "a short cytoplasmic", "short cytoplasmic tail.", "cytoplasmic tail. they", "tail. they bind", "they bind carbohydrate", "bind carbohydrate structures", "carbohydrate structures through", "structures through a", "through a ca2+", "a ca2+ dependent", "ca2+ dependent domain", "domain the", "the minimal sugar", "minimal sugar structure", "sugar structure recognised", "structure recognised fulfilled", "recognised fulfilled by", "fulfilled by slea", "by slea and", "slea and slex.", "and slex. selectins", "slex. selectins are", "selectins are found", "are found on", "found on endothelial", "on endothelial cells", "cells platelets", "platelets and leukocytes", "and leukocytes and", "leukocytes and are", "and are involved", "are involved in", "involved in trafficking", "in trafficking of", "trafficking of cells", "of cells of", "cells of the", "of the innate", "the innate immune", "innate immune system", "system t", "t lymphocytes and", "lymphocytes and platelets", "platelets thereby", "thereby playing important", "playing important roles", "important roles in", "roles in chronic", "in chronic and", "chronic and acute", "and acute inflammation", "acute inflammation and", "inflammation and haemostasis.", "and haemostasis. selectins", "haemostasis. selectins also", "selectins also play", "also play a", "play a role", "a role in", "role in cancer", "in cancer progression.", "cancer progression. metastasis", "progression. metastasis is", "metastasis is facilitated", "is facilitated by", "facilitated by cell", "by cell cell", "cell cell interactions", "cell interactions between", "interactions between cancer", "between cancer cells", "cells and endothelial", "and endothelial cells", "endothelial cells in", "cells in distant", "in distant tissues.", "distant tissues. in", "tissues. in addition", "addition cancer", "cancer cell interactions", "cell interactions with", "interactions with platelets", "with platelets and", "and leukocytes contribute", "leukocytes contribute to", "contribute to cancer", "to cancer cell", "cancer cell adhesion", "adhesion extravasation", "extravasation and", "and the establishment", "the establishment of", "establishment of metastatic", "of metastatic lesions.", "metastatic lesions. targeting", "lesions. targeting selectins", "targeting selectins and", "selectins and their", "and their ligands", "their ligands as", "ligands as well", "as well as", "well as the", "as the enzymes", "the enzymes involved", "enzymes involved in", "involved in their", "in their generation", "generation in", "in particular sialyl", "particular sialyl transferases", "transferases could", "could be a", "be a useful", "a useful strategy", "useful strategy in", "strategy in cancer", "in cancer treatment", "treatment ley", "2003 laubli", "laubli & borsig", "& borsig 2010", "2010 cheung", "cheung et al.", "et al. 2011", "2011 natoli", "natoli et al.", "et al. 2016", "2016 trinchera", "trinchera et al.", "et al. 2017", "al. 2017 .", "the lewis antigen system", "lewis antigen system is", "antigen system is a", "system is a human", "is a human blood", "a human blood group", "human blood group system", "blood group system based", "group system based upon", "system based upon genes", "based upon genes on", "upon genes on chromosome", "genes on chromosome 19", "on chromosome 19 p13.3", "19 p13.3 the", "p13.3 the fut3", "the fut3 gene aka", "fut3 gene aka the", "gene aka the le", "aka the le gene", "le gene and", "gene and 19q13.3", "19q13.3 fut2", "fut2 gene aka the", "gene aka the se", "aka the se gene", "the se gene .", "se gene . both", "gene . both genes", ". both genes are", "both genes are expressed", "genes are expressed in", "are expressed in glandular", "expressed in glandular epithelia", "in glandular epithelia and", "glandular epithelia and have", "epithelia and have dominant", "and have dominant alleles", "dominant alleles le", "alleles le and", "and se respectively", "respectively coding for", "coding for enzymes with", "for enzymes with fucosyltransferase", "enzymes with fucosyltransferase activity", "with fucosyltransferase activity and", "fucosyltransferase activity and recessive", "activity and recessive alleles", "recessive alleles le", "respectively that are", "that are non functional.", "are non functional. there", "non functional. there are", "functional. there are two", "there are two main", "are two main lewis", "two main lewis antigens", "lewis antigens lewis", "antigens lewis a", "lewis a and lewis", "a and lewis b", "and lewis b which", "lewis b which can", "b which can result", "which can result in", "can result in three", "result in three common", "in three common phenotypes:", "three common phenotypes: le", "common phenotypes: le a+b", "a b+ and", "b+ and le", "and le a b", "a b .", "b . lewis", ". lewis antigens are", "lewis antigens are components", "antigens are components of", "are components of exocrine", "components of exocrine epithelial", "of exocrine epithelial secretions", "epithelial secretions and", "secretions and can", "and can be adsorbed", "can be adsorbed onto", "be adsorbed onto the", "adsorbed onto the surfaces", "onto the surfaces of", "the surfaces of red", "surfaces of red blood", "of red blood cells", "blood cells rbcs", "rbcs therefore", "therefore are not produced", "are not produced directly", "not produced directly by", "produced directly by rbcs", "directly by rbcs themselves", "rbcs themselves ewald", "themselves ewald &", "ewald & sumner 2016", "& sumner 2016 .

              the", "sumner 2016 .

              the same", "2016 .

              the same two", ".

              the same two oligosaccharides", "two oligosaccharides type", "oligosaccharides type 1", "type 1 and type", "1 and type 2", "type 2 used", "2 used to", "used to determine abo", "to determine abo blood", "determine abo blood types", "abo blood types are", "blood types are also", "types are also utilised", "are also utilised by", "also utilised by the", "utilised by the lewis", "by the lewis system.", "the lewis system. fucosyltransferase", "lewis system. fucosyltransferase 3", "fucosyltransferase 3 fut3", "le adds fucose", "adds fucose to type", "fucose to type 1", "to type 1 chains", "type 1 chains to", "1 chains to form", "chains to form the", "to form the lewis", "form the lewis a", "the lewis a antigen", "a antigen lea", "antigen lea .", "lea . if the", ". if the individual", "if the individual is", "the individual is a", "individual is a non", "is a non secretor", "non secretor lacks", "secretor lacks the", "lacks the se gene", "se gene homozygous", "gene homozygous sese", "sese lea", "lea is adsorbed onto", "is adsorbed onto the", "adsorbed onto the red", "onto the red cell", "red cell and", "cell and that", "and that individual is", "that individual is lea", "individual is lea type.", "is lea type. approximately", "lea type. approximately 80%", "type. approximately 80% of", "approximately 80% of the", "80% of the population", "of the population has", "the population has the", "population has the se", "has the se gene.", "the se gene. functional", "se gene. functional fucosyltransferase", "gene. functional fucosyltransferase 2", "fucosyltransferase 2 fut2", "se adds a", "adds a fucose to", "a fucose to lea", "fucose to lea to", "to lea to form", "lea to form leb.", "to form leb. both", "form leb. both lea", "leb. both lea and", "both lea and leb", "lea and leb present", "and leb present in", "leb present in the", "present in the plasma", "in the plasma of", "the plasma of secretors", "plasma of secretors but", "of secretors but lea", "secretors but lea preferentially", "but lea preferentially adsorbs", "lea preferentially adsorbs onto", "preferentially adsorbs onto the", "adsorbs onto the rbc", "onto the rbc and", "the rbc and therefore", "and therefore the", "therefore the individual", "the individual types as", "individual types as leb.", "types as leb. other", "as leb. other futs", "other futs especially", "futs especially fut4", "especially fut4 can", "fut4 can add", "can add a fucose", "add a fucose to", "a fucose to type", "fucose to type 2", "to type 2 chains", "type 2 chains to", "2 chains to form", "form the lewis x", "the lewis x antigen", "x antigen lex", "antigen lex .", "lex . further fucosylation", ". further fucosylation of", "further fucosylation of lex", "fucosylation of lex by", "of lex by fut2", "lex by fut2 produces", "by fut2 produces the", "fut2 produces the lewis", "produces the lewis y", "the lewis y antigen", "y antigen ley", "antigen ley .", "ley . lex", ". lex and", "lex and ley are", "and ley are structural", "ley are structural isomers", "are structural isomers of", "structural isomers of lea", "isomers of lea and", "of lea and leb.", "lea and leb. the", "and leb. the formation", "leb. the formation of", "the formation of ley", "formation of ley is", "of ley is controlled", "ley is controlled by", "is controlled by se/se", "controlled by se/se as", "by se/se as in", "se/se as in the", "as in the case", "in the case for", "the case for leb.", "case for leb. lea", "for leb. lea and", "leb. lea and lex", "lea and lex antigens", "and lex antigens can", "lex antigens can also", "antigens can also undergo", "can also undergo sialation", "also undergo sialation to", "undergo sialation to produce", "sialation to produce sialated", "to produce sialated forms", "produce sialated forms of", "sialated forms of these", "forms of these antigens.

              aberrant", "of these antigens.

              aberrant glycosylation", "these antigens.

              aberrant glycosylation of", "antigens.

              aberrant glycosylation of tumour", "glycosylation of tumour cells", "of tumour cells is", "tumour cells is recognised", "cells is recognised as", "is recognised as a", "recognised as a feature", "as a feature of", "a feature of cancer", "feature of cancer pathogenesis.", "of cancer pathogenesis. overexpression", "cancer pathogenesis. overexpression of", "pathogenesis. overexpression of fucosylated", "overexpression of fucosylated and", "of fucosylated and sialated", "fucosylated and sialated lewis", "and sialated lewis antigens", "sialated lewis antigens frequently", "lewis antigens frequently occurs", "antigens frequently occurs on", "frequently occurs on the", "occurs on the surfaces", "on the surfaces of", "the surfaces of cancer", "surfaces of cancer cells", "of cancer cells and", "cancer cells and is", "cells and is mainly", "and is mainly attributed", "is mainly attributed to", "mainly attributed to upregulated", "attributed to upregulated expression", "to upregulated expression of", "upregulated expression of the", "expression of the relevant", "of the relevant fucosyltransferases", "relevant fucosyltransferases futs", "fucosyltransferases futs .", "futs . the", ". the sialyl", "the sialyl lewis a", "sialyl lewis a antigen", "a antigen slea", "slea also", "also known as the", "known as the ca19", "as the ca19 9", "the ca19 9 antigen", "9 antigen is", "antigen is the", "is the most common", "the most common tumour", "most common tumour marker", "common tumour marker used", "tumour marker used primarily", "marker used primarily in", "used primarily in the", "primarily in the management", "in the management of", "the management of pancreatic", "management of pancreatic and", "of pancreatic and gastrointestinal", "pancreatic and gastrointestinal cancers", "and gastrointestinal cancers worldwide", "cancers worldwide magnani", "worldwide magnani 2004", "magnani 2004 blanas", "2004 blanas et", "blanas et al. 2018", "et al. 2018 .

              selectins", "2018 .

              selectins l", "l e", "e and p", "p selectin are", "selectin are type", "are type i membrane", "type i membrane proteins", "i membrane proteins composed", "membrane proteins composed of", "proteins composed of long", "composed of long n", "of long n terminus", "long n terminus c", "n terminus c type", "terminus c type lectin", "c type lectin domains", "type lectin domains protruding", "lectin domains protruding into", "domains protruding into the", "protruding into the extracellular", "into the extracellular space", "the extracellular space and", "extracellular space and with", "space and with a", "and with a short", "with a short cytoplasmic", "a short cytoplasmic tail.", "short cytoplasmic tail. they", "cytoplasmic tail. they bind", "tail. they bind carbohydrate", "they bind carbohydrate structures", "bind carbohydrate structures through", "carbohydrate structures through a", "structures through a ca2+", "through a ca2+ dependent", "a ca2+ dependent domain", "dependent domain the", "domain the minimal", "the minimal sugar structure", "minimal sugar structure recognised", "sugar structure recognised fulfilled", "structure recognised fulfilled by", "recognised fulfilled by slea", "fulfilled by slea and", "by slea and slex.", "slea and slex. selectins", "and slex. selectins are", "slex. selectins are found", "selectins are found on", "are found on endothelial", "found on endothelial cells", "endothelial cells platelets", "cells platelets and", "platelets and leukocytes and", "and leukocytes and are", "leukocytes and are involved", "and are involved in", "are involved in trafficking", "involved in trafficking of", "in trafficking of cells", "trafficking of cells of", "of cells of the", "cells of the innate", "of the innate immune", "the innate immune system", "immune system t", "system t lymphocytes", "t lymphocytes and platelets", "and platelets thereby", "platelets thereby playing", "thereby playing important roles", "playing important roles in", "important roles in chronic", "roles in chronic and", "in chronic and acute", "chronic and acute inflammation", "and acute inflammation and", "acute inflammation and haemostasis.", "inflammation and haemostasis. selectins", "and haemostasis. selectins also", "haemostasis. selectins also play", "selectins also play a", "also play a role", "play a role in", "a role in cancer", "role in cancer progression.", "in cancer progression. metastasis", "cancer progression. metastasis is", "progression. metastasis is facilitated", "metastasis is facilitated by", "is facilitated by cell", "facilitated by cell cell", "by cell cell interactions", "cell cell interactions between", "cell interactions between cancer", "interactions between cancer cells", "between cancer cells and", "cancer cells and endothelial", "cells and endothelial cells", "and endothelial cells in", "endothelial cells in distant", "cells in distant tissues.", "in distant tissues. in", "distant tissues. in addition", "in addition cancer", "addition cancer cell", "cancer cell interactions with", "cell interactions with platelets", "interactions with platelets and", "with platelets and leukocytes", "platelets and leukocytes contribute", "and leukocytes contribute to", "leukocytes contribute to cancer", "contribute to cancer cell", "to cancer cell adhesion", "cell adhesion extravasation", "extravasation and the", "and the establishment of", "the establishment of metastatic", "establishment of metastatic lesions.", "of metastatic lesions. targeting", "metastatic lesions. targeting selectins", "lesions. targeting selectins and", "targeting selectins and their", "selectins and their ligands", "and their ligands as", "their ligands as well", "ligands as well as", "as well as the", "well as the enzymes", "as the enzymes involved", "the enzymes involved in", "enzymes involved in their", "involved in their generation", "their generation in", "generation in particular", "in particular sialyl transferases", "sialyl transferases could", "transferases could be", "could be a useful", "be a useful strategy", "a useful strategy in", "useful strategy in cancer", "strategy in cancer treatment", "cancer treatment ley", "treatment ley 2003", "ley 2003 laubli", "2003 laubli &", "laubli & borsig 2010", "borsig 2010 cheung", "2010 cheung et", "cheung et al. 2011", "al. 2011 natoli", "2011 natoli et", "natoli et al. 2016", "al. 2016 trinchera", "2016 trinchera et", "trinchera et al. 2017", "et al. 2017 .", "the lewis antigen system is", "lewis antigen system is a", "antigen system is a human", "system is a human blood", "is a human blood group", "a human blood group system", "human blood group system based", "blood group system based upon", "group system based upon genes", "system based upon genes on", "based upon genes on chromosome", "upon genes on chromosome 19", "genes on chromosome 19 p13.3", "chromosome 19 p13.3 the", "19 p13.3 the fut3", "p13.3 the fut3 gene", "the fut3 gene aka the", "fut3 gene aka the le", "gene aka the le gene", "the le gene and", "le gene and 19q13.3", "and 19q13.3 fut2", "19q13.3 fut2 gene", "fut2 gene aka the se", "gene aka the se gene", "aka the se gene .", "the se gene . both", "se gene . both genes", "gene . both genes are", ". both genes are expressed", "both genes are expressed in", "genes are expressed in glandular", "are expressed in glandular epithelia", "expressed in glandular epithelia and", "in glandular epithelia and have", "glandular epithelia and have dominant", "epithelia and have dominant alleles", "have dominant alleles le", "dominant alleles le and", "alleles le and se", "le and se respectively", "se respectively coding", "respectively coding for enzymes", "coding for enzymes with fucosyltransferase", "for enzymes with fucosyltransferase activity", "enzymes with fucosyltransferase activity and", "with fucosyltransferase activity and recessive", "fucosyltransferase activity and recessive alleles", "and recessive alleles le", "recessive alleles le and", "se respectively that", "respectively that are non", "that are non functional. there", "are non functional. there are", "non functional. there are two", "functional. there are two main", "there are two main lewis", "are two main lewis antigens", "main lewis antigens lewis", "lewis antigens lewis a", "antigens lewis a and", "lewis a and lewis b", "a and lewis b which", "and lewis b which can", "lewis b which can result", "b which can result in", "which can result in three", "can result in three common", "result in three common phenotypes:", "in three common phenotypes: le", "three common phenotypes: le a+b", "a+b le", "le a b+ and", "a b+ and le", "b+ and le a", "le a b .", "a b . lewis", "b . lewis antigens", ". lewis antigens are components", "lewis antigens are components of", "antigens are components of exocrine", "are components of exocrine epithelial", "components of exocrine epithelial secretions", "exocrine epithelial secretions and", "epithelial secretions and can", "secretions and can be", "and can be adsorbed onto", "can be adsorbed onto the", "be adsorbed onto the surfaces", "adsorbed onto the surfaces of", "onto the surfaces of red", "the surfaces of red blood", "surfaces of red blood cells", "red blood cells rbcs", "rbcs therefore are", "therefore are not produced directly", "are not produced directly by", "not produced directly by rbcs", "produced directly by rbcs themselves", "by rbcs themselves ewald", "rbcs themselves ewald &", "themselves ewald & sumner", "ewald & sumner 2016 .

              the", "& sumner 2016 .

              the same", "sumner 2016 .

              the same two", "2016 .

              the same two oligosaccharides", "same two oligosaccharides type", "two oligosaccharides type 1", "oligosaccharides type 1 and", "type 1 and type 2", "and type 2 used", "type 2 used to", "2 used to determine", "used to determine abo blood", "to determine abo blood types", "determine abo blood types are", "abo blood types are also", "blood types are also utilised", "types are also utilised by", "are also utilised by the", "also utilised by the lewis", "utilised by the lewis system.", "by the lewis system. fucosyltransferase", "the lewis system. fucosyltransferase 3", "system. fucosyltransferase 3 fut3", "3 fut3 le", "fut3 le adds", "le adds fucose to", "adds fucose to type 1", "fucose to type 1 chains", "to type 1 chains to", "type 1 chains to form", "1 chains to form the", "chains to form the lewis", "to form the lewis a", "form the lewis a antigen", "lewis a antigen lea", "a antigen lea .", "antigen lea . if", "lea . if the individual", ". if the individual is", "if the individual is a", "the individual is a non", "individual is a non secretor", "a non secretor lacks", "non secretor lacks the", "secretor lacks the se", "the se gene homozygous", "se gene homozygous sese", "homozygous sese lea", "sese lea is", "lea is adsorbed onto the", "is adsorbed onto the red", "adsorbed onto the red cell", "the red cell and", "red cell and that", "cell and that individual", "and that individual is lea", "that individual is lea type.", "individual is lea type. approximately", "is lea type. approximately 80%", "lea type. approximately 80% of", "type. approximately 80% of the", "approximately 80% of the population", "80% of the population has", "of the population has the", "the population has the se", "population has the se gene.", "has the se gene. functional", "the se gene. functional fucosyltransferase", "se gene. functional fucosyltransferase 2", "functional fucosyltransferase 2 fut2", "2 fut2 se", "fut2 se adds", "se adds a fucose", "adds a fucose to lea", "a fucose to lea to", "fucose to lea to form", "to lea to form leb.", "lea to form leb. both", "to form leb. both lea", "form leb. both lea and", "leb. both lea and leb", "both lea and leb present", "lea and leb present in", "and leb present in the", "leb present in the plasma", "present in the plasma of", "in the plasma of secretors", "the plasma of secretors but", "plasma of secretors but lea", "of secretors but lea preferentially", "secretors but lea preferentially adsorbs", "but lea preferentially adsorbs onto", "lea preferentially adsorbs onto the", "preferentially adsorbs onto the rbc", "adsorbs onto the rbc and", "onto the rbc and therefore", "rbc and therefore the", "and therefore the individual", "therefore the individual types", "the individual types as leb.", "individual types as leb. other", "types as leb. other futs", "leb. other futs especially", "other futs especially fut4", "especially fut4 can add", "fut4 can add a", "can add a fucose to", "add a fucose to type", "a fucose to type 2", "fucose to type 2 chains", "to type 2 chains to", "type 2 chains to form", "2 chains to form the", "to form the lewis x", "form the lewis x antigen", "lewis x antigen lex", "x antigen lex .", "antigen lex . further", "lex . further fucosylation of", ". further fucosylation of lex", "further fucosylation of lex by", "fucosylation of lex by fut2", "of lex by fut2 produces", "lex by fut2 produces the", "by fut2 produces the lewis", "fut2 produces the lewis y", "produces the lewis y antigen", "lewis y antigen ley", "y antigen ley .", "ley . lex and", ". lex and ley", "lex and ley are structural", "and ley are structural isomers", "ley are structural isomers of", "are structural isomers of lea", "structural isomers of lea and", "isomers of lea and leb.", "of lea and leb. the", "lea and leb. the formation", "and leb. the formation of", "leb. the formation of ley", "the formation of ley is", "formation of ley is controlled", "of ley is controlled by", "ley is controlled by se/se", "is controlled by se/se as", "controlled by se/se as in", "by se/se as in the", "se/se as in the case", "as in the case for", "in the case for leb.", "the case for leb. lea", "case for leb. lea and", "for leb. lea and lex", "leb. lea and lex antigens", "lea and lex antigens can", "and lex antigens can also", "lex antigens can also undergo", "antigens can also undergo sialation", "can also undergo sialation to", "also undergo sialation to produce", "undergo sialation to produce sialated", "sialation to produce sialated forms", "to produce sialated forms of", "produce sialated forms of these", "sialated forms of these antigens.

              aberrant", "forms of these antigens.

              aberrant glycosylation", "of these antigens.

              aberrant glycosylation of", "these antigens.

              aberrant glycosylation of tumour", "antigens.

              aberrant glycosylation of tumour cells", "glycosylation of tumour cells is", "of tumour cells is recognised", "tumour cells is recognised as", "cells is recognised as a", "is recognised as a feature", "recognised as a feature of", "as a feature of cancer", "a feature of cancer pathogenesis.", "feature of cancer pathogenesis. overexpression", "of cancer pathogenesis. overexpression of", "cancer pathogenesis. overexpression of fucosylated", "pathogenesis. overexpression of fucosylated and", "overexpression of fucosylated and sialated", "of fucosylated and sialated lewis", "fucosylated and sialated lewis antigens", "and sialated lewis antigens frequently", "sialated lewis antigens frequently occurs", "lewis antigens frequently occurs on", "antigens frequently occurs on the", "frequently occurs on the surfaces", "occurs on the surfaces of", "on the surfaces of cancer", "the surfaces of cancer cells", "surfaces of cancer cells and", "of cancer cells and is", "cancer cells and is mainly", "cells and is mainly attributed", "and is mainly attributed to", "is mainly attributed to upregulated", "mainly attributed to upregulated expression", "attributed to upregulated expression of", "to upregulated expression of the", "upregulated expression of the relevant", "expression of the relevant fucosyltransferases", "the relevant fucosyltransferases futs", "relevant fucosyltransferases futs .", "futs . the sialyl", ". the sialyl lewis", "the sialyl lewis a antigen", "lewis a antigen slea", "slea also known", "also known as the ca19", "known as the ca19 9", "as the ca19 9 antigen", "ca19 9 antigen is", "9 antigen is the", "antigen is the most", "is the most common tumour", "the most common tumour marker", "most common tumour marker used", "common tumour marker used primarily", "tumour marker used primarily in", "marker used primarily in the", "used primarily in the management", "primarily in the management of", "in the management of pancreatic", "the management of pancreatic and", "management of pancreatic and gastrointestinal", "of pancreatic and gastrointestinal cancers", "pancreatic and gastrointestinal cancers worldwide", "gastrointestinal cancers worldwide magnani", "cancers worldwide magnani 2004", "magnani 2004 blanas et", "2004 blanas et al.", "blanas et al. 2018 .

              selectins", "al. 2018 .

              selectins l", "e and p selectin", "and p selectin are", "p selectin are type", "selectin are type i", "are type i membrane proteins", "type i membrane proteins composed", "i membrane proteins composed of", "membrane proteins composed of long", "proteins composed of long n", "composed of long n terminus", "of long n terminus c", "long n terminus c type", "n terminus c type lectin", "terminus c type lectin domains", "c type lectin domains protruding", "type lectin domains protruding into", "lectin domains protruding into the", "domains protruding into the extracellular", "protruding into the extracellular space", "into the extracellular space and", "the extracellular space and with", "extracellular space and with a", "space and with a short", "and with a short cytoplasmic", "with a short cytoplasmic tail.", "a short cytoplasmic tail. they", "short cytoplasmic tail. they bind", "cytoplasmic tail. they bind carbohydrate", "tail. they bind carbohydrate structures", "they bind carbohydrate structures through", "bind carbohydrate structures through a", "carbohydrate structures through a ca2+", "structures through a ca2+ dependent", "through a ca2+ dependent domain", "ca2+ dependent domain the", "dependent domain the minimal", "domain the minimal sugar", "the minimal sugar structure recognised", "minimal sugar structure recognised fulfilled", "sugar structure recognised fulfilled by", "structure recognised fulfilled by slea", "recognised fulfilled by slea and", "fulfilled by slea and slex.", "by slea and slex. selectins", "slea and slex. selectins are", "and slex. selectins are found", "slex. selectins are found on", "selectins are found on endothelial", "are found on endothelial cells", "on endothelial cells platelets", "endothelial cells platelets and", "cells platelets and leukocytes", "platelets and leukocytes and are", "and leukocytes and are involved", "leukocytes and are involved in", "and are involved in trafficking", "are involved in trafficking of", "involved in trafficking of cells", "in trafficking of cells of", "trafficking of cells of the", "of cells of the innate", "cells of the innate immune", "of the innate immune system", "innate immune system t", "immune system t lymphocytes", "system t lymphocytes and", "lymphocytes and platelets thereby", "and platelets thereby playing", "platelets thereby playing important", "thereby playing important roles in", "playing important roles in chronic", "important roles in chronic and", "roles in chronic and acute", "in chronic and acute inflammation", "chronic and acute inflammation and", "and acute inflammation and haemostasis.", "acute inflammation and haemostasis. selectins", "inflammation and haemostasis. selectins also", "and haemostasis. selectins also play", "haemostasis. selectins also play a", "selectins also play a role", "also play a role in", "play a role in cancer", "a role in cancer progression.", "role in cancer progression. metastasis", "in cancer progression. metastasis is", "cancer progression. metastasis is facilitated", "progression. metastasis is facilitated by", "metastasis is facilitated by cell", "is facilitated by cell cell", "facilitated by cell cell interactions", "by cell cell interactions between", "cell cell interactions between cancer", "cell interactions between cancer cells", "interactions between cancer cells and", "between cancer cells and endothelial", "cancer cells and endothelial cells", "cells and endothelial cells in", "and endothelial cells in distant", "endothelial cells in distant tissues.", "cells in distant tissues. in", "in distant tissues. in addition", "tissues. in addition cancer", "in addition cancer cell", "addition cancer cell interactions", "cancer cell interactions with platelets", "cell interactions with platelets and", "interactions with platelets and leukocytes", "with platelets and leukocytes contribute", "platelets and leukocytes contribute to", "and leukocytes contribute to cancer", "leukocytes contribute to cancer cell", "contribute to cancer cell adhesion", "cancer cell adhesion extravasation", "adhesion extravasation and", "extravasation and the establishment", "and the establishment of metastatic", "the establishment of metastatic lesions.", "establishment of metastatic lesions. targeting", "of metastatic lesions. targeting selectins", "metastatic lesions. targeting selectins and", "lesions. targeting selectins and their", "targeting selectins and their ligands", "selectins and their ligands as", "and their ligands as well", "their ligands as well as", "ligands as well as the", "as well as the enzymes", "well as the enzymes involved", "as the enzymes involved in", "the enzymes involved in their", "enzymes involved in their generation", "in their generation in", "their generation in particular", "generation in particular sialyl", "particular sialyl transferases could", "sialyl transferases could be", "transferases could be a", "could be a useful strategy", "be a useful strategy in", "a useful strategy in cancer", "useful strategy in cancer treatment", "in cancer treatment ley", "cancer treatment ley 2003", "ley 2003 laubli &", "2003 laubli & borsig", "& borsig 2010 cheung", "borsig 2010 cheung et", "2010 cheung et al.", "et al. 2011 natoli", "al. 2011 natoli et", "2011 natoli et al.", "et al. 2016 trinchera", "al. 2016 trinchera et", "2016 trinchera et al.", "trinchera et al. 2017 ." ] }, { "record_id": "GLY_000594_1_1204", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "913709", "r hsa", "hsa 913709", "r hsa 913709" ] }, { "record_id": "GLY_000594_1_1204", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "o linked", "linked glycosylation", "glycosylation of", "of mucins", "o linked glycosylation", "linked glycosylation of", "glycosylation of mucins", "o linked glycosylation of", "linked glycosylation of mucins", "o linked glycosylation of mucins", "mucins are", "are a", "a family", "family of", "of high", "high molecular", "molecular weight", "heavily glycosylated", "produced by", "by epithelial", "epithelial tissues", "tissues in", "in most", "most metazoa.", "metazoa. mucins'", "mucins' key", "key characteristic", "characteristic is", "is their", "their ability", "ability to", "to form", "form gels", "therefore they", "they are", "a key", "key component", "component in", "most gel", "gel like", "like secretions", "serving functions", "functions from", "from lubrication", "lubrication to", "to cell", "cell signalling", "signalling to", "to forming", "forming chemical", "chemical barriers.", "barriers. to", "to date", "there are", "are approximately", "approximately 20", "20 genes", "genes that", "that express", "express mucins.", "mucins. mature", "mature mucins", "are composed", "composed of", "of two", "two distinct", "distinct regions:
              ", "regions:
              1", "the amino", "and carboxy", "carboxy terminal", "terminal regions", "regions are", "are very", "very lightly", "lightly glycosylated", "but rich", "rich in", "in cysteines.", "cysteines. the", "the cysteine", "cysteine residues", "residues participate", "participate in", "in establishing", "establishing disulfide", "disulfide linkages", "linkages within", "within and", "and among", "among mucin", "mucin monomers.
              ", "monomers.
              2", "a large", "large central", "central region", "region rich", "in serine", "threonine and", "and proline", "proline residues", "residues called", "called the", "the variable", "variable number", "number of", "of tandem", "tandem repeat", "region which", "which can", "can become", "become heavily", "heavily o", "o glycosylated", "glycosylated with", "with hundreds", "hundreds of", "of o", "o galnac", "galnac glycans.
              ", "glycans.
              n", "n acetyl", "acetyl galactosamine", "is the", "the first", "first glycan", "glycan to", "to be", "be attached", "forming the", "the simplest", "simplest mucin", "mucin o", "o glycan.", "glycan. after", "after this", "several different", "different pathways", "pathways are", "are possible", "possible generating", "generating \\core\\", "\\core\\ structures.", "structures. four", "four core", "core structures", "structures are", "are commonly", "commonly formed", "several others", "others are", "possible but", "but infrequent.", "infrequent. o", "linked glycans", "glycans are", "are often", "often capped", "capped by", "by the", "the addition", "addition of", "of a", "a sialic", "sialic acid", "acid residue", "terminating the", "of any", "any more", "more o", "o glycans", "brockhausen et", "et al", "tarp and", "and clausen", "2008 .", "mucins are a", "are a family", "a family of", "family of high", "of high molecular", "high molecular weight", "weight heavily", "glycosylated proteins", "proteins glycoconjugates", "glycoconjugates produced", "produced by epithelial", "by epithelial tissues", "epithelial tissues in", "tissues in most", "in most metazoa.", "most metazoa. mucins'", "metazoa. mucins' key", "mucins' key characteristic", "key characteristic is", "characteristic is their", "is their ability", "their ability to", "ability to form", "to form gels", "gels therefore", "therefore they are", "they are a", "are a key", "a key component", "key component in", "component in most", "in most gel", "most gel like", "gel like secretions", "secretions serving", "serving functions from", "functions from lubrication", "from lubrication to", "lubrication to cell", "to cell signalling", "cell signalling to", "signalling to forming", "to forming chemical", "forming chemical barriers.", "chemical barriers. to", "barriers. to date", "date there", "there are approximately", "are approximately 20", "approximately 20 genes", "20 genes that", "genes that express", "that express mucins.", "express mucins. mature", "mucins. mature mucins", "mature mucins are", "mucins are composed", "are composed of", "composed of two", "of two distinct", "two distinct regions:
              ", "distinct regions:
              1", "1 the", "amino and", "and carboxy terminal", "carboxy terminal regions", "terminal regions are", "regions are very", "are very lightly", "very lightly glycosylated", "glycosylated but", "but rich in", "rich in cysteines.", "in cysteines. the", "cysteines. the cysteine", "the cysteine residues", "cysteine residues participate", "residues participate in", "participate in establishing", "in establishing disulfide", "establishing disulfide linkages", "disulfide linkages within", "linkages within and", "within and among", "and among mucin", "among mucin monomers.
              ", "mucin monomers.
              2", "2 a", "a large central", "large central region", "central region rich", "region rich in", "rich in serine", "serine threonine", "threonine and proline", "and proline residues", "proline residues called", "residues called the", "called the variable", "the variable number", "variable number of", "number of tandem", "of tandem repeat", "repeat vntr", "vntr region", "region which can", "which can become", "can become heavily", "become heavily o", "heavily o glycosylated", "o glycosylated with", "glycosylated with hundreds", "with hundreds of", "hundreds of o", "of o galnac", "o galnac glycans.
              ", "galnac glycans.
              n", "glycans.
              n acetyl", "n acetyl galactosamine", "galactosamine galnac", "galnac is", "is the first", "the first glycan", "first glycan to", "glycan to be", "to be attached", "attached forming", "forming the simplest", "the simplest mucin", "simplest mucin o", "mucin o glycan.", "o glycan. after", "glycan. after this", "this several", "several different pathways", "different pathways are", "pathways are possible", "are possible generating", "possible generating \\core\\", "generating \\core\\ structures.", "\\core\\ structures. four", "structures. four core", "four core structures", "core structures are", "structures are commonly", "are commonly formed", "formed several", "several others are", "others are possible", "are possible but", "possible but infrequent.", "but infrequent. o", "infrequent. o linked", "o linked glycans", "linked glycans are", "glycans are often", "are often capped", "often capped by", "capped by the", "by the addition", "the addition of", "addition of a", "of a sialic", "a sialic acid", "sialic acid residue", "residue terminating", "terminating the addition", "addition of any", "of any more", "any more o", "more o glycans", "glycans brockhausen", "brockhausen et al", "al 2009", "2009 tarp", "tarp and clausen", "clausen 2008", "mucins are a family", "are a family of", "a family of high", "family of high molecular", "of high molecular weight", "molecular weight heavily", "weight heavily glycosylated", "heavily glycosylated proteins", "glycoconjugates produced by", "produced by epithelial tissues", "by epithelial tissues in", "epithelial tissues in most", "tissues in most metazoa.", "in most metazoa. mucins'", "most metazoa. mucins' key", "metazoa. mucins' key characteristic", "mucins' key characteristic is", "key characteristic is their", "characteristic is their ability", "is their ability to", "their ability to form", "ability to form gels", "form gels therefore", "gels therefore they", "therefore they are a", "they are a key", "are a key component", "a key component in", "key component in most", "component in most gel", "in most gel like", "most gel like secretions", "like secretions serving", "secretions serving functions", "serving functions from lubrication", "functions from lubrication to", "from lubrication to cell", "lubrication to cell signalling", "to cell signalling to", "cell signalling to forming", "signalling to forming chemical", "to forming chemical barriers.", "forming chemical barriers. to", "chemical barriers. to date", "to date there", "date there are", "there are approximately 20", "are approximately 20 genes", "approximately 20 genes that", "20 genes that express", "genes that express mucins.", "that express mucins. mature", "express mucins. mature mucins", "mucins. mature mucins are", "mature mucins are composed", "mucins are composed of", "are composed of two", "composed of two distinct", "of two distinct regions:
              ", "two distinct regions:
              1", "regions:
              1 the", "1 the amino", "the amino and", "amino and carboxy", "and carboxy terminal regions", "carboxy terminal regions are", "terminal regions are very", "regions are very lightly", "are very lightly glycosylated", "lightly glycosylated but", "glycosylated but rich", "but rich in cysteines.", "rich in cysteines. the", "in cysteines. the cysteine", "cysteines. the cysteine residues", "the cysteine residues participate", "cysteine residues participate in", "residues participate in establishing", "participate in establishing disulfide", "in establishing disulfide linkages", "establishing disulfide linkages within", "disulfide linkages within and", "linkages within and among", "within and among mucin", "and among mucin monomers.
              ", "among mucin monomers.
              2", "monomers.
              2 a", "2 a large", "a large central region", "large central region rich", "central region rich in", "region rich in serine", "in serine threonine", "serine threonine and", "threonine and proline residues", "and proline residues called", "proline residues called the", "residues called the variable", "called the variable number", "the variable number of", "variable number of tandem", "number of tandem repeat", "tandem repeat vntr", "vntr region which", "region which can become", "which can become heavily", "can become heavily o", "become heavily o glycosylated", "heavily o glycosylated with", "o glycosylated with hundreds", "glycosylated with hundreds of", "with hundreds of o", "hundreds of o galnac", "of o galnac glycans.
              ", "o galnac glycans.
              n", "galnac glycans.
              n acetyl", "glycans.
              n acetyl galactosamine", "acetyl galactosamine galnac", "galnac is the", "is the first glycan", "the first glycan to", "first glycan to be", "glycan to be attached", "be attached forming", "attached forming the", "forming the simplest mucin", "the simplest mucin o", "simplest mucin o glycan.", "mucin o glycan. after", "o glycan. after this", "after this several", "this several different", "several different pathways are", "different pathways are possible", "pathways are possible generating", "are possible generating \\core\\", "possible generating \\core\\ structures.", "generating \\core\\ structures. four", "\\core\\ structures. four core", "structures. four core structures", "four core structures are", "core structures are commonly", "structures are commonly formed", "commonly formed several", "formed several others", "several others are possible", "others are possible but", "are possible but infrequent.", "possible but infrequent. o", "but infrequent. o linked", "infrequent. o linked glycans", "o linked glycans are", "linked glycans are often", "glycans are often capped", "are often capped by", "often capped by the", "capped by the addition", "by the addition of", "the addition of a", "addition of a sialic", "of a sialic acid", "a sialic acid residue", "acid residue terminating", "residue terminating the", "terminating the addition of", "the addition of any", "addition of any more", "of any more o", "any more o glycans", "o glycans brockhausen", "glycans brockhausen et", "et al 2009", "2009 tarp and", "and clausen 2008", "clausen 2008 .", "mucins are a family of", "are a family of high", "a family of high molecular", "family of high molecular weight", "high molecular weight heavily", "molecular weight heavily glycosylated", "glycosylated proteins glycoconjugates", "proteins glycoconjugates produced", "glycoconjugates produced by epithelial", "produced by epithelial tissues in", "by epithelial tissues in most", "epithelial tissues in most metazoa.", "tissues in most metazoa. mucins'", "in most metazoa. mucins' key", "most metazoa. mucins' key characteristic", "metazoa. mucins' key characteristic is", "mucins' key characteristic is their", "key characteristic is their ability", "characteristic is their ability to", "is their ability to form", "their ability to form gels", "to form gels therefore", "form gels therefore they", "gels therefore they are", "therefore they are a key", "they are a key component", "are a key component in", "a key component in most", "key component in most gel", "component in most gel like", "in most gel like secretions", "gel like secretions serving", "like secretions serving functions", "secretions serving functions from", "serving functions from lubrication to", "functions from lubrication to cell", "from lubrication to cell signalling", "lubrication to cell signalling to", "to cell signalling to forming", "cell signalling to forming chemical", "signalling to forming chemical barriers.", "to forming chemical barriers. to", "forming chemical barriers. to date", "barriers. to date there", "to date there are", "date there are approximately", "there are approximately 20 genes", "are approximately 20 genes that", "approximately 20 genes that express", "20 genes that express mucins.", "genes that express mucins. mature", "that express mucins. mature mucins", "express mucins. mature mucins are", "mucins. mature mucins are composed", "mature mucins are composed of", "mucins are composed of two", "are composed of two distinct", "composed of two distinct regions:
              ", "of two distinct regions:
              1", "distinct regions:
              1 the", "regions:
              1 the amino", "the amino and carboxy", "amino and carboxy terminal", "and carboxy terminal regions are", "carboxy terminal regions are very", "terminal regions are very lightly", "regions are very lightly glycosylated", "very lightly glycosylated but", "lightly glycosylated but rich", "glycosylated but rich in", "but rich in cysteines. the", "rich in cysteines. the cysteine", "in cysteines. the cysteine residues", "cysteines. the cysteine residues participate", "the cysteine residues participate in", "cysteine residues participate in establishing", "residues participate in establishing disulfide", "participate in establishing disulfide linkages", "in establishing disulfide linkages within", "establishing disulfide linkages within and", "disulfide linkages within and among", "linkages within and among mucin", "within and among mucin monomers.
              ", "and among mucin monomers.
              2", "mucin monomers.
              2 a", "monomers.
              2 a large", "2 a large central", "a large central region rich", "large central region rich in", "central region rich in serine", "rich in serine threonine", "in serine threonine and", "serine threonine and proline", "threonine and proline residues called", "and proline residues called the", "proline residues called the variable", "residues called the variable number", "called the variable number of", "the variable number of tandem", "variable number of tandem repeat", "of tandem repeat vntr", "repeat vntr region", "vntr region which can", "region which can become heavily", "which can become heavily o", "can become heavily o glycosylated", "become heavily o glycosylated with", "heavily o glycosylated with hundreds", "o glycosylated with hundreds of", "glycosylated with hundreds of o", "with hundreds of o galnac", "hundreds of o galnac glycans.
              ", "of o galnac glycans.
              n", "o galnac glycans.
              n acetyl", "galnac glycans.
              n acetyl galactosamine", "n acetyl galactosamine galnac", "galactosamine galnac is", "galnac is the first", "is the first glycan to", "the first glycan to be", "first glycan to be attached", "to be attached forming", "be attached forming the", "attached forming the simplest", "forming the simplest mucin o", "the simplest mucin o glycan.", "simplest mucin o glycan. after", "mucin o glycan. after this", "glycan. after this several", "after this several different", "this several different pathways", "several different pathways are possible", "different pathways are possible generating", "pathways are possible generating \\core\\", "are possible generating \\core\\ structures.", "possible generating \\core\\ structures. four", "generating \\core\\ structures. four core", "\\core\\ structures. four core structures", "structures. four core structures are", "four core structures are commonly", "core structures are commonly formed", "are commonly formed several", "commonly formed several others", "formed several others are", "several others are possible but", "others are possible but infrequent.", "are possible but infrequent. o", "possible but infrequent. o linked", "but infrequent. o linked glycans", "infrequent. o linked glycans are", "o linked glycans are often", "linked glycans are often capped", "glycans are often capped by", "are often capped by the", "often capped by the addition", "capped by the addition of", "by the addition of a", "the addition of a sialic", "addition of a sialic acid", "of a sialic acid residue", "sialic acid residue terminating", "acid residue terminating the", "residue terminating the addition", "terminating the addition of any", "the addition of any more", "addition of any more o", "of any more o glycans", "more o glycans brockhausen", "o glycans brockhausen et", "glycans brockhausen et al", "brockhausen et al 2009", "al 2009 tarp", "2009 tarp and clausen", "tarp and clausen 2008", "and clausen 2008 ." ] }, { "record_id": "GLY_000594_1_1205", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "917937", "r hsa", "hsa 917937", "r hsa 917937" ] }, { "record_id": "GLY_000594_1_1205", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "iron uptake", "uptake and", "and transport", "iron uptake and", "uptake and transport", "iron uptake and transport", "the transport", "transport of", "of iron", "iron between", "between cells", "cells is", "is mediated", "mediated by", "by transferrin.", "transferrin. however", "iron can", "can also", "also enter", "enter and", "and leave", "leave cells", "cells not", "not only", "only by", "by itself", "but also", "also in", "in the", "the form", "form of", "of heme", "heme and", "and siderophores.", "siderophores. when", "when entering", "entering the", "the cell", "cell via", "via the", "the main", "main path", "by transferrin", "transferrin endocytosis", "its goal", "goal is", "is not", "not the", "still elusive", "chelated iron", "iron pool", "pool in", "the cytosol", "cytosol nor", "nor the", "the lysosomes", "lysosomes but", "but the", "the mitochondria", "where heme", "heme is", "is synthesized", "synthesized and", "and iron", "iron sulfur", "sulfur clusters", "clusters are", "are assembled", "kurz et", "et al", "al 2008", "hower et", "al 2009", "richardson et", "al 2010", "2010 .", "the transport of", "transport of iron", "of iron between", "iron between cells", "between cells is", "cells is mediated", "is mediated by", "mediated by transferrin.", "by transferrin. however", "however iron", "iron can also", "can also enter", "also enter and", "enter and leave", "and leave cells", "leave cells not", "cells not only", "not only by", "only by itself", "itself but", "but also in", "also in the", "in the form", "the form of", "form of heme", "of heme and", "heme and siderophores.", "and siderophores. when", "siderophores. when entering", "when entering the", "entering the cell", "the cell via", "cell via the", "via the main", "the main path", "path by", "by transferrin endocytosis", "its goal is", "goal is not", "is not the", "the still", "elusive chelated", "chelated iron pool", "iron pool in", "pool in the", "in the cytosol", "the cytosol nor", "cytosol nor the", "nor the lysosomes", "the lysosomes but", "lysosomes but the", "but the mitochondria", "mitochondria where", "where heme is", "heme is synthesized", "is synthesized and", "synthesized and iron", "and iron sulfur", "iron sulfur clusters", "sulfur clusters are", "clusters are assembled", "assembled kurz", "kurz et al", "et al 2008", "2008 hower", "hower et al", "et al 2009", "2009 richardson", "richardson et al", "et al 2010", "al 2010 .", "the transport of iron", "transport of iron between", "of iron between cells", "iron between cells is", "between cells is mediated", "cells is mediated by", "is mediated by transferrin.", "mediated by transferrin. however", "transferrin. however iron", "however iron can", "iron can also enter", "can also enter and", "also enter and leave", "enter and leave cells", "and leave cells not", "leave cells not only", "cells not only by", "not only by itself", "by itself but", "itself but also", "but also in the", "also in the form", "in the form of", "the form of heme", "form of heme and", "of heme and siderophores.", "heme and siderophores. when", "and siderophores. when entering", "siderophores. when entering the", "when entering the cell", "entering the cell via", "the cell via the", "cell via the main", "via the main path", "main path by", "path by transferrin", "endocytosis its", "its goal is not", "goal is not the", "not the still", "the still elusive", "still elusive chelated", "elusive chelated iron", "chelated iron pool in", "iron pool in the", "pool in the cytosol", "in the cytosol nor", "the cytosol nor the", "cytosol nor the lysosomes", "nor the lysosomes but", "the lysosomes but the", "lysosomes but the mitochondria", "the mitochondria where", "mitochondria where heme", "where heme is synthesized", "heme is synthesized and", "is synthesized and iron", "synthesized and iron sulfur", "and iron sulfur clusters", "iron sulfur clusters are", "sulfur clusters are assembled", "are assembled kurz", "assembled kurz et", "kurz et al 2008", "al 2008 hower", "2008 hower et", "hower et al 2009", "al 2009 richardson", "2009 richardson et", "richardson et al 2010", "et al 2010 .", "the transport of iron between", "transport of iron between cells", "of iron between cells is", "iron between cells is mediated", "between cells is mediated by", "cells is mediated by transferrin.", "is mediated by transferrin. however", "by transferrin. however iron", "transferrin. however iron can", "however iron can also", "iron can also enter and", "can also enter and leave", "also enter and leave cells", "enter and leave cells not", "and leave cells not only", "leave cells not only by", "cells not only by itself", "only by itself but", "by itself but also", "itself but also in", "but also in the form", "also in the form of", "in the form of heme", "the form of heme and", "form of heme and siderophores.", "of heme and siderophores. when", "heme and siderophores. when entering", "and siderophores. when entering the", "siderophores. when entering the cell", "when entering the cell via", "entering the cell via the", "the cell via the main", "cell via the main path", "the main path by", "main path by transferrin", "path by transferrin endocytosis", "transferrin endocytosis its", "endocytosis its goal", "its goal is not the", "is not the still", "not the still elusive", "still elusive chelated iron", "elusive chelated iron pool", "chelated iron pool in the", "iron pool in the cytosol", "pool in the cytosol nor", "in the cytosol nor the", "the cytosol nor the lysosomes", "cytosol nor the lysosomes but", "nor the lysosomes but the", "the lysosomes but the mitochondria", "but the mitochondria where", "the mitochondria where heme", "mitochondria where heme is", "where heme is synthesized and", "heme is synthesized and iron", "is synthesized and iron sulfur", "synthesized and iron sulfur clusters", "and iron sulfur clusters are", "iron sulfur clusters are assembled", "clusters are assembled kurz", "are assembled kurz et", "assembled kurz et al", "et al 2008 hower", "al 2008 hower et", "2008 hower et al", "et al 2009 richardson", "al 2009 richardson et", "2009 richardson et al", "richardson et al 2010 ." ] }, { "record_id": "GLY_000594_1_1206", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "918233", "r hsa", "hsa 918233", "r hsa 918233" ] }, { "record_id": "GLY_000594_1_1206", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "traf3 dependent", "dependent irf", "irf activation", "activation pathway", "traf3 dependent irf", "dependent irf activation", "irf activation pathway", "traf3 dependent irf activation", "dependent irf activation pathway", "traf3 dependent irf activation pathway", "mavs via", "via its", "its traf", "traf interaction", "interaction motif", "directly interacts", "interacts with", "with traf3", "traf3 and", "and recruits", "recruits traf3", "traf3 to", "to the", "the signaling", "signaling complex.", "complex. traf3", "traf3 acts", "acts as", "as a", "a scaffold", "scaffold for", "for the", "the assembly", "assembly of", "of a", "a signaling", "signaling complex", "complex composed", "composed of", "of ikk", "ikk epsilon/tbk1", "leading to", "the activation", "activation of", "of transcription", "transcription factors", "factors irf3/irf7.", "mavs via its", "via its traf", "its traf interaction", "traf interaction motif", "motif tim", "tim directly", "directly interacts with", "interacts with traf3", "with traf3 and", "traf3 and recruits", "and recruits traf3", "recruits traf3 to", "traf3 to the", "to the signaling", "the signaling complex.", "signaling complex. traf3", "complex. traf3 acts", "traf3 acts as", "acts as a", "as a scaffold", "a scaffold for", "scaffold for the", "for the assembly", "the assembly of", "assembly of a", "of a signaling", "a signaling complex", "signaling complex composed", "complex composed of", "composed of ikk", "of ikk epsilon/tbk1", "epsilon/tbk1 leading", "leading to the", "to the activation", "the activation of", "activation of transcription", "of transcription factors", "transcription factors irf3/irf7.", "mavs via its traf", "via its traf interaction", "its traf interaction motif", "interaction motif tim", "tim directly interacts", "directly interacts with traf3", "interacts with traf3 and", "with traf3 and recruits", "traf3 and recruits traf3", "and recruits traf3 to", "recruits traf3 to the", "traf3 to the signaling", "to the signaling complex.", "the signaling complex. traf3", "signaling complex. traf3 acts", "complex. traf3 acts as", "traf3 acts as a", "acts as a scaffold", "as a scaffold for", "a scaffold for the", "scaffold for the assembly", "for the assembly of", "the assembly of a", "assembly of a signaling", "of a signaling complex", "a signaling complex composed", "signaling complex composed of", "complex composed of ikk", "composed of ikk epsilon/tbk1", "ikk epsilon/tbk1 leading", "epsilon/tbk1 leading to", "leading to the activation", "to the activation of", "the activation of transcription", "activation of transcription factors", "of transcription factors irf3/irf7.", "mavs via its traf interaction", "via its traf interaction motif", "traf interaction motif tim", "motif tim directly", "tim directly interacts with", "directly interacts with traf3 and", "interacts with traf3 and recruits", "with traf3 and recruits traf3", "traf3 and recruits traf3 to", "and recruits traf3 to the", "recruits traf3 to the signaling", "traf3 to the signaling complex.", "to the signaling complex. traf3", "the signaling complex. traf3 acts", "signaling complex. traf3 acts as", "complex. traf3 acts as a", "traf3 acts as a scaffold", "acts as a scaffold for", "as a scaffold for the", "a scaffold for the assembly", "scaffold for the assembly of", "for the assembly of a", "the assembly of a signaling", "assembly of a signaling complex", "of a signaling complex composed", "a signaling complex composed of", "signaling complex composed of ikk", "complex composed of ikk epsilon/tbk1", "of ikk epsilon/tbk1 leading", "ikk epsilon/tbk1 leading to", "epsilon/tbk1 leading to the", "leading to the activation of", "to the activation of transcription", "the activation of transcription factors", "activation of transcription factors irf3/irf7." ] }, { "record_id": "GLY_000594_1_1207", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "933541", "r hsa", "hsa 933541", "r hsa 933541" ] }, { "record_id": "GLY_000594_1_1207", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "traf6 mediated", "mediated irf7", "irf7 activation", "traf6 mediated irf7", "mediated irf7 activation", "traf6 mediated irf7 activation", "traf6 is", "is crucial", "crucial for", "for both", "both ddx58", "rig i", "and ifih1", "mediated antiviral", "antiviral responses.", "responses. the", "the absence", "absence of", "of traf6", "traf6 resulted", "resulted in", "in enhanced", "enhanced viral", "viral replication", "replication and", "and a", "a significant", "significant reduction", "reduction in", "in the", "the production", "production of", "of type", "type i", "i ifns", "ifns and", "and il6", "il6 after", "after infection", "infection with", "with rna", "rna virus.", "virus. activation", "activation of", "of nf", "nf kb", "kb and", "and irf7", "but not", "not that", "that of", "of irf3", "was significantly", "significantly impaired", "impaired during", "during rig", "rig like", "like helicases", "signaling in", "of traf6.", "traf6. traf6", "traf6 induced", "induced activation", "of irf", "irf is", "is likely", "likely to", "to be", "be specific", "specific for", "for irf7", "while traf3", "traf3 is", "is thought", "thought to", "to activate", "activate both", "both irf3", "irf3 and", "and irf7.", "irf7. these", "these results", "results strongly", "strongly suggest", "suggest that", "that the", "the traf6", "and traf3", "traf3 dependent", "dependent pathways", "pathways are", "are likely", "to bifurcate", "bifurcate at", "at mitochondrial", "mitochondrial antiviral", "antiviral signaling", "signaling protein", "protein mavs", "ips 1", "but to", "to converge", "converge later", "later at", "at irf7", "irf7 in", "in order", "order to", "to co", "co operatively", "operatively induce", "induce sufficient", "sufficient production", "ifns during", "during rlh", "rlh signaling.", "traf6 is crucial", "is crucial for", "crucial for both", "for both ddx58", "ddx58 rig", "ifih1 mda5", "mda5 mediated", "mediated antiviral responses.", "antiviral responses. the", "responses. the absence", "the absence of", "absence of traf6", "of traf6 resulted", "traf6 resulted in", "resulted in enhanced", "in enhanced viral", "enhanced viral replication", "viral replication and", "replication and a", "and a significant", "a significant reduction", "significant reduction in", "reduction in the", "in the production", "the production of", "production of type", "of type i", "type i ifns", "i ifns and", "ifns and il6", "and il6 after", "il6 after infection", "after infection with", "infection with rna", "with rna virus.", "rna virus. activation", "virus. activation of", "activation of nf", "of nf kb", "nf kb and", "kb and irf7", "irf7 but", "but not that", "not that of", "that of irf3", "irf3 was", "was significantly impaired", "significantly impaired during", "impaired during rig", "during rig like", "rig like helicases", "helicases rlhs", "rlhs signaling", "signaling in the", "in the absence", "absence of traf6.", "of traf6. traf6", "traf6. traf6 induced", "traf6 induced activation", "induced activation of", "activation of irf", "of irf is", "irf is likely", "is likely to", "likely to be", "to be specific", "be specific for", "specific for irf7", "irf7 while", "while traf3 is", "traf3 is thought", "is thought to", "thought to activate", "to activate both", "activate both irf3", "both irf3 and", "irf3 and irf7.", "and irf7. these", "irf7. these results", "these results strongly", "results strongly suggest", "strongly suggest that", "suggest that the", "that the traf6", "traf6 and", "and traf3 dependent", "traf3 dependent pathways", "dependent pathways are", "pathways are likely", "are likely to", "likely to bifurcate", "to bifurcate at", "bifurcate at mitochondrial", "at mitochondrial antiviral", "mitochondrial antiviral signaling", "antiviral signaling protein", "signaling protein mavs", "mavs ips", "but to converge", "to converge later", "converge later at", "later at irf7", "at irf7 in", "irf7 in order", "in order to", "order to co", "to co operatively", "co operatively induce", "operatively induce sufficient", "induce sufficient production", "sufficient production of", "i ifns during", "ifns during rlh", "during rlh signaling.", "traf6 is crucial for", "is crucial for both", "crucial for both ddx58", "both ddx58 rig", "ddx58 rig i", "i and", "and ifih1 mda5", "mda5 mediated antiviral", "mediated antiviral responses. the", "antiviral responses. the absence", "responses. the absence of", "the absence of traf6", "absence of traf6 resulted", "of traf6 resulted in", "traf6 resulted in enhanced", "resulted in enhanced viral", "in enhanced viral replication", "enhanced viral replication and", "viral replication and a", "replication and a significant", "and a significant reduction", "a significant reduction in", "significant reduction in the", "reduction in the production", "in the production of", "the production of type", "production of type i", "of type i ifns", "type i ifns and", "i ifns and il6", "ifns and il6 after", "and il6 after infection", "il6 after infection with", "after infection with rna", "infection with rna virus.", "with rna virus. activation", "rna virus. activation of", "virus. activation of nf", "activation of nf kb", "of nf kb and", "nf kb and irf7", "and irf7 but", "irf7 but not", "but not that of", "not that of irf3", "of irf3 was", "irf3 was significantly", "was significantly impaired during", "significantly impaired during rig", "impaired during rig like", "during rig like helicases", "like helicases rlhs", "rlhs signaling in", "signaling in the absence", "in the absence of", "the absence of traf6.", "absence of traf6. traf6", "of traf6. traf6 induced", "traf6. traf6 induced activation", "traf6 induced activation of", "induced activation of irf", "activation of irf is", "of irf is likely", "irf is likely to", "is likely to be", "likely to be specific", "to be specific for", "be specific for irf7", "for irf7 while", "irf7 while traf3", "while traf3 is thought", "traf3 is thought to", "is thought to activate", "thought to activate both", "to activate both irf3", "activate both irf3 and", "both irf3 and irf7.", "irf3 and irf7. these", "and irf7. these results", "irf7. these results strongly", "these results strongly suggest", "results strongly suggest that", "strongly suggest that the", "suggest that the traf6", "the traf6 and", "traf6 and traf3", "and traf3 dependent pathways", "traf3 dependent pathways are", "dependent pathways are likely", "pathways are likely to", "are likely to bifurcate", "likely to bifurcate at", "to bifurcate at mitochondrial", "bifurcate at mitochondrial antiviral", "at mitochondrial antiviral signaling", "mitochondrial antiviral signaling protein", "antiviral signaling protein mavs", "protein mavs ips", "mavs ips 1", "1 but", "but to converge later", "to converge later at", "converge later at irf7", "later at irf7 in", "at irf7 in order", "irf7 in order to", "in order to co", "order to co operatively", "to co operatively induce", "co operatively induce sufficient", "operatively induce sufficient production", "induce sufficient production of", "sufficient production of type", "type i ifns during", "i ifns during rlh", "ifns during rlh signaling.", "traf6 is crucial for both", "is crucial for both ddx58", "for both ddx58 rig", "both ddx58 rig i", "rig i and", "i and ifih1", "ifih1 mda5 mediated", "mda5 mediated antiviral responses.", "mediated antiviral responses. the absence", "antiviral responses. the absence of", "responses. the absence of traf6", "the absence of traf6 resulted", "absence of traf6 resulted in", "of traf6 resulted in enhanced", "traf6 resulted in enhanced viral", "resulted in enhanced viral replication", "in enhanced viral replication and", "enhanced viral replication and a", "viral replication and a significant", "replication and a significant reduction", "and a significant reduction in", "a significant reduction in the", "significant reduction in the production", "reduction in the production of", "in the production of type", "the production of type i", "production of type i ifns", "of type i ifns and", "type i ifns and il6", "i ifns and il6 after", "ifns and il6 after infection", "and il6 after infection with", "il6 after infection with rna", "after infection with rna virus.", "infection with rna virus. activation", "with rna virus. activation of", "rna virus. activation of nf", "virus. activation of nf kb", "activation of nf kb and", "of nf kb and irf7", "kb and irf7 but", "and irf7 but not", "irf7 but not that", "but not that of irf3", "that of irf3 was", "of irf3 was significantly", "irf3 was significantly impaired", "was significantly impaired during rig", "significantly impaired during rig like", "impaired during rig like helicases", "rig like helicases rlhs", "helicases rlhs signaling", "rlhs signaling in the", "signaling in the absence of", "in the absence of traf6.", "the absence of traf6. traf6", "absence of traf6. traf6 induced", "of traf6. traf6 induced activation", "traf6. traf6 induced activation of", "traf6 induced activation of irf", "induced activation of irf is", "activation of irf is likely", "of irf is likely to", "irf is likely to be", "is likely to be specific", "likely to be specific for", "to be specific for irf7", "specific for irf7 while", "for irf7 while traf3", "irf7 while traf3 is", "while traf3 is thought to", "traf3 is thought to activate", "is thought to activate both", "thought to activate both irf3", "to activate both irf3 and", "activate both irf3 and irf7.", "both irf3 and irf7. these", "irf3 and irf7. these results", "and irf7. these results strongly", "irf7. these results strongly suggest", "these results strongly suggest that", "results strongly suggest that the", "strongly suggest that the traf6", "that the traf6 and", "the traf6 and traf3", "traf6 and traf3 dependent", "and traf3 dependent pathways are", "traf3 dependent pathways are likely", "dependent pathways are likely to", "pathways are likely to bifurcate", "are likely to bifurcate at", "likely to bifurcate at mitochondrial", "to bifurcate at mitochondrial antiviral", "bifurcate at mitochondrial antiviral signaling", "at mitochondrial antiviral signaling protein", "mitochondrial antiviral signaling protein mavs", "signaling protein mavs ips", "protein mavs ips 1", "ips 1 but", "1 but to", "but to converge later at", "to converge later at irf7", "converge later at irf7 in", "later at irf7 in order", "at irf7 in order to", "irf7 in order to co", "in order to co operatively", "order to co operatively induce", "to co operatively induce sufficient", "co operatively induce sufficient production", "operatively induce sufficient production of", "induce sufficient production of type", "sufficient production of type i", "of type i ifns during", "type i ifns during rlh", "i ifns during rlh signaling." ] }, { "record_id": "GLY_000594_1_1208", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "937042", "r hsa", "hsa 937042", "r hsa 937042" ] }, { "record_id": "GLY_000594_1_1208", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "irak2 mediated", "mediated activation", "activation of", "of tak1", "tak1 complex", "irak2 mediated activation", "mediated activation of", "activation of tak1", "of tak1 complex", "irak2 mediated activation of", "mediated activation of tak1", "activation of tak1 complex", "irak2 mediated activation of tak1", "mediated activation of tak1 complex", "although irak", "irak 1", "1 was", "was originally", "originally thought", "thought to", "to be", "be a", "a key", "key mediator", "mediator of", "of traf6", "traf6 activation", "activation in", "in the", "the il1r/tlr", "il1r/tlr signaling", "dong w", "w et", "et al.", "al. 2006", "recent studies", "studies showed", "showed that", "that irak", "irak 2", "but not", "not irak", "led to", "to traf6", "traf6 polyubiquitination", "keating se", "se et", "et al", "al 2007", "2007 .", ". irak", "2 loss", "loss of", "of function", "function mutants", "with mutated", "mutated traf6", "traf6 binding", "binding motifs", "could no", "no longer", "longer activate", "activate nf", "nf kb", "kb and", "and could", "longer stimulate", "stimulate traf", "traf 6", "6 ubiquitination", ". furthermore", "the proxyvirus", "proxyvirus protein", "protein a52", "an inhibitor", "inhibitor of", "of all", "all il", "il 1r/tlr", "1r/tlr pathways", "pathways to", "to nf", "kb activation", "was found", "found to", "to interact", "interact with", "with both", "both irak", "2 and", "and traf6", "irak 1.", "1. further", "further work", "work showed", "that a52", "a52 inhibits", "inhibits irak", "2 functions", "whereas association", "association with", "with traf6", "traf6 results", "results in", "in a52", "a52 induced", "induced mapk", "mapk activation.", "activation. the", "the strong", "strong inhibition", "inhibition effect", "effect of", "of a52", "a52 was", "was also", "also observed", "observed on", "on the", "the tlr3", "tlr3 nfkb", "nfkb axis", "axis and", "and this", "this observation", "observation led", "to the", "the discovery", "discovery that", "2 is", "is recruited", "recruited to", "to tlr3", "tlr3 to", "to activate", ". thus", "a52 possibly", "possibly inhibits", "inhibits myd88", "myd88 independent", "independent tlr3", "tlr3 pathways", "via targeting", "targeting irak", "2 as", "as it", "it does", "does for", "for other", "other il", "although it", "it remains", "remains unclear", "unclear how", "how irak", "is involved", "involved in", "in tlr3", "tlr3 signaling.

              irak", "signaling.

              irak 2", "2 was", "was shown", "shown to", "to have", "have two", "two traf6", "motifs that", "that are", "are responsible", "responsible for", "for initiating", "initiating traf6", "traf6 signaling", "signaling transduction", "ye h", "h et", "al 2002", "2002 .", "although irak 1", "irak 1 was", "1 was originally", "was originally thought", "originally thought to", "thought to be", "to be a", "be a key", "a key mediator", "key mediator of", "mediator of traf6", "of traf6 activation", "traf6 activation in", "activation in the", "in the il1r/tlr", "the il1r/tlr signaling", "signaling dong", "dong w et", "w et al.", "et al. 2006", "recent studies showed", "studies showed that", "showed that irak", "that irak 2", "2 but", "but not irak", "not irak 1", "1 led", "led to traf6", "to traf6 polyubiquitination", "polyubiquitination keating", "keating se et", "se et al", "et al 2007", "al 2007 .", "2007 . irak", ". irak 2", "irak 2 loss", "2 loss of", "loss of function", "of function mutants", "mutants with", "with mutated traf6", "mutated traf6 binding", "traf6 binding motifs", "motifs could", "could no longer", "no longer activate", "longer activate nf", "activate nf kb", "nf kb and", "kb and could", "and could no", "no longer stimulate", "longer stimulate traf", "stimulate traf 6", "traf 6 ubiquitination", "ubiquitination keating", "2007 . furthermore", "furthermore the", "the proxyvirus protein", "proxyvirus protein a52", "an inhibitor of", "inhibitor of all", "of all il", "all il 1r/tlr", "il 1r/tlr pathways", "1r/tlr pathways to", "pathways to nf", "to nf kb", "nf kb activation", "activation was", "was found to", "found to interact", "to interact with", "interact with both", "with both irak", "both irak 2", "irak 2 and", "2 and traf6", "traf6 but", "not irak 1.", "irak 1. further", "1. further work", "further work showed", "work showed that", "showed that a52", "that a52 inhibits", "a52 inhibits irak", "inhibits irak 2", "irak 2 functions", "functions whereas", "whereas association with", "association with traf6", "with traf6 results", "traf6 results in", "results in a52", "in a52 induced", "a52 induced mapk", "induced mapk activation.", "mapk activation. the", "activation. the strong", "the strong inhibition", "strong inhibition effect", "inhibition effect of", "effect of a52", "of a52 was", "a52 was also", "was also observed", "also observed on", "observed on the", "on the tlr3", "the tlr3 nfkb", "tlr3 nfkb axis", "nfkb axis and", "axis and this", "and this observation", "this observation led", "observation led to", "led to the", "to the discovery", "the discovery that", "discovery that irak", "irak 2 is", "2 is recruited", "is recruited to", "recruited to tlr3", "to tlr3 to", "tlr3 to activate", "to activate nf", "kb keating", "2007 . thus", "thus a52", "a52 possibly inhibits", "possibly inhibits myd88", "inhibits myd88 independent", "myd88 independent tlr3", "independent tlr3 pathways", "tlr3 pathways to", "kb via", "via targeting irak", "targeting irak 2", "irak 2 as", "2 as it", "as it does", "it does for", "does for other", "for other il", "other il 1r/tlr", "pathways although", "although it remains", "it remains unclear", "remains unclear how", "unclear how irak", "how irak 2", "2 is involved", "is involved in", "involved in tlr3", "in tlr3 signaling.

              irak", "tlr3 signaling.

              irak 2", "signaling.

              irak 2 was", "2 was shown", "was shown to", "shown to have", "to have two", "have two traf6", "two traf6 binding", "binding motifs that", "motifs that are", "that are responsible", "are responsible for", "responsible for initiating", "for initiating traf6", "initiating traf6 signaling", "traf6 signaling transduction", "transduction ye", "ye h et", "h et al", "et al 2002", "al 2002 .", "although irak 1 was", "irak 1 was originally", "1 was originally thought", "was originally thought to", "originally thought to be", "thought to be a", "to be a key", "be a key mediator", "a key mediator of", "key mediator of traf6", "mediator of traf6 activation", "of traf6 activation in", "traf6 activation in the", "activation in the il1r/tlr", "in the il1r/tlr signaling", "il1r/tlr signaling dong", "signaling dong w", "dong w et al.", "w et al. 2006", "2006 recent", "recent studies showed that", "studies showed that irak", "showed that irak 2", "irak 2 but", "2 but not", "but not irak 1", "irak 1 led", "1 led to", "led to traf6 polyubiquitination", "traf6 polyubiquitination keating", "polyubiquitination keating se", "keating se et al", "se et al 2007", "et al 2007 .", "al 2007 . irak", "2007 . irak 2", ". irak 2 loss", "irak 2 loss of", "2 loss of function", "loss of function mutants", "function mutants with", "mutants with mutated", "with mutated traf6 binding", "mutated traf6 binding motifs", "binding motifs could", "motifs could no", "could no longer activate", "no longer activate nf", "longer activate nf kb", "activate nf kb and", "nf kb and could", "kb and could no", "and could no longer", "could no longer stimulate", "no longer stimulate traf", "longer stimulate traf 6", "stimulate traf 6 ubiquitination", "6 ubiquitination keating", "ubiquitination keating se", "al 2007 . furthermore", ". furthermore the", "furthermore the proxyvirus", "the proxyvirus protein a52", "a52 an", "an inhibitor of all", "inhibitor of all il", "of all il 1r/tlr", "all il 1r/tlr pathways", "il 1r/tlr pathways to", "1r/tlr pathways to nf", "pathways to nf kb", "to nf kb activation", "kb activation was", "activation was found", "was found to interact", "found to interact with", "to interact with both", "interact with both irak", "with both irak 2", "both irak 2 and", "irak 2 and traf6", "and traf6 but", "traf6 but not", "but not irak 1.", "not irak 1. further", "irak 1. further work", "1. further work showed", "further work showed that", "work showed that a52", "showed that a52 inhibits", "that a52 inhibits irak", "a52 inhibits irak 2", "inhibits irak 2 functions", "2 functions whereas", "functions whereas association", "whereas association with traf6", "association with traf6 results", "with traf6 results in", "traf6 results in a52", "results in a52 induced", "in a52 induced mapk", "a52 induced mapk activation.", "induced mapk activation. the", "mapk activation. the strong", "activation. the strong inhibition", "the strong inhibition effect", "strong inhibition effect of", "inhibition effect of a52", "effect of a52 was", "of a52 was also", "a52 was also observed", "was also observed on", "also observed on the", "observed on the tlr3", "on the tlr3 nfkb", "the tlr3 nfkb axis", "tlr3 nfkb axis and", "nfkb axis and this", "axis and this observation", "and this observation led", "this observation led to", "observation led to the", "led to the discovery", "to the discovery that", "the discovery that irak", "discovery that irak 2", "that irak 2 is", "irak 2 is recruited", "2 is recruited to", "is recruited to tlr3", "recruited to tlr3 to", "to tlr3 to activate", "tlr3 to activate nf", "to activate nf kb", "nf kb keating", "kb keating se", "al 2007 . thus", ". thus a52", "thus a52 possibly", "a52 possibly inhibits myd88", "possibly inhibits myd88 independent", "inhibits myd88 independent tlr3", "myd88 independent tlr3 pathways", "independent tlr3 pathways to", "tlr3 pathways to nf", "nf kb via", "kb via targeting", "via targeting irak 2", "targeting irak 2 as", "irak 2 as it", "2 as it does", "as it does for", "it does for other", "does for other il", "for other il 1r/tlr", "other il 1r/tlr pathways", "1r/tlr pathways although", "pathways although it", "although it remains unclear", "it remains unclear how", "remains unclear how irak", "unclear how irak 2", "how irak 2 is", "irak 2 is involved", "2 is involved in", "is involved in tlr3", "involved in tlr3 signaling.

              irak", "in tlr3 signaling.

              irak 2", "tlr3 signaling.

              irak 2 was", "signaling.

              irak 2 was shown", "2 was shown to", "was shown to have", "shown to have two", "to have two traf6", "have two traf6 binding", "two traf6 binding motifs", "traf6 binding motifs that", "binding motifs that are", "motifs that are responsible", "that are responsible for", "are responsible for initiating", "responsible for initiating traf6", "for initiating traf6 signaling", "initiating traf6 signaling transduction", "signaling transduction ye", "transduction ye h", "ye h et al", "h et al 2002", "et al 2002 .", "although irak 1 was originally", "irak 1 was originally thought", "1 was originally thought to", "was originally thought to be", "originally thought to be a", "thought to be a key", "to be a key mediator", "be a key mediator of", "a key mediator of traf6", "key mediator of traf6 activation", "mediator of traf6 activation in", "of traf6 activation in the", "traf6 activation in the il1r/tlr", "activation in the il1r/tlr signaling", "the il1r/tlr signaling dong", "il1r/tlr signaling dong w", "signaling dong w et", "dong w et al. 2006", "al. 2006 recent", "2006 recent studies", "recent studies showed that irak", "studies showed that irak 2", "that irak 2 but", "irak 2 but not", "2 but not irak", "not irak 1 led", "irak 1 led to", "1 led to traf6", "to traf6 polyubiquitination keating", "traf6 polyubiquitination keating se", "polyubiquitination keating se et", "keating se et al 2007", "se et al 2007 .", "et al 2007 . irak", "al 2007 . irak 2", "2007 . irak 2 loss", ". irak 2 loss of", "irak 2 loss of function", "2 loss of function mutants", "of function mutants with", "function mutants with mutated", "mutants with mutated traf6", "with mutated traf6 binding motifs", "traf6 binding motifs could", "binding motifs could no", "motifs could no longer", "could no longer activate nf", "no longer activate nf kb", "longer activate nf kb and", "activate nf kb and could", "nf kb and could no", "kb and could no longer", "and could no longer stimulate", "could no longer stimulate traf", "no longer stimulate traf 6", "longer stimulate traf 6 ubiquitination", "traf 6 ubiquitination keating", "6 ubiquitination keating se", "ubiquitination keating se et", "et al 2007 . furthermore", "2007 . furthermore the", ". furthermore the proxyvirus", "furthermore the proxyvirus protein", "protein a52 an", "a52 an inhibitor", "an inhibitor of all il", "inhibitor of all il 1r/tlr", "of all il 1r/tlr pathways", "all il 1r/tlr pathways to", "il 1r/tlr pathways to nf", "1r/tlr pathways to nf kb", "pathways to nf kb activation", "nf kb activation was", "kb activation was found", "activation was found to", "was found to interact with", "found to interact with both", "to interact with both irak", "interact with both irak 2", "with both irak 2 and", "both irak 2 and traf6", "2 and traf6 but", "and traf6 but not", "traf6 but not irak", "but not irak 1. further", "not irak 1. further work", "irak 1. further work showed", "1. further work showed that", "further work showed that a52", "work showed that a52 inhibits", "showed that a52 inhibits irak", "that a52 inhibits irak 2", "a52 inhibits irak 2 functions", "irak 2 functions whereas", "2 functions whereas association", "functions whereas association with", "whereas association with traf6 results", "association with traf6 results in", "with traf6 results in a52", "traf6 results in a52 induced", "results in a52 induced mapk", "in a52 induced mapk activation.", "a52 induced mapk activation. the", "induced mapk activation. the strong", "mapk activation. the strong inhibition", "activation. the strong inhibition effect", "the strong inhibition effect of", "strong inhibition effect of a52", "inhibition effect of a52 was", "effect of a52 was also", "of a52 was also observed", "a52 was also observed on", "was also observed on the", "also observed on the tlr3", "observed on the tlr3 nfkb", "on the tlr3 nfkb axis", "the tlr3 nfkb axis and", "tlr3 nfkb axis and this", "nfkb axis and this observation", "axis and this observation led", "and this observation led to", "this observation led to the", "observation led to the discovery", "led to the discovery that", "to the discovery that irak", "the discovery that irak 2", "discovery that irak 2 is", "that irak 2 is recruited", "irak 2 is recruited to", "2 is recruited to tlr3", "is recruited to tlr3 to", "recruited to tlr3 to activate", "to tlr3 to activate nf", "tlr3 to activate nf kb", "activate nf kb keating", "nf kb keating se", "kb keating se et", "et al 2007 . thus", "2007 . thus a52", ". thus a52 possibly", "thus a52 possibly inhibits", "a52 possibly inhibits myd88 independent", "possibly inhibits myd88 independent tlr3", "inhibits myd88 independent tlr3 pathways", "myd88 independent tlr3 pathways to", "independent tlr3 pathways to nf", "tlr3 pathways to nf kb", "to nf kb via", "nf kb via targeting", "kb via targeting irak", "via targeting irak 2 as", "targeting irak 2 as it", "irak 2 as it does", "2 as it does for", "as it does for other", "it does for other il", "does for other il 1r/tlr", "for other il 1r/tlr pathways", "il 1r/tlr pathways although", "1r/tlr pathways although it", "pathways although it remains", "although it remains unclear how", "it remains unclear how irak", "remains unclear how irak 2", "unclear how irak 2 is", "how irak 2 is involved", "irak 2 is involved in", "2 is involved in tlr3", "is involved in tlr3 signaling.

              irak", "involved in tlr3 signaling.

              irak 2", "in tlr3 signaling.

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"xanthine and", "aldehyde oxidases.", "oxidases. this", "this means", "in humans", "humans we", "we find", "find sulfurated", "sulfurated instead", "instead of", "of desulfurated", "desulfurated molybdenum", "cofactor on", "on these", "these two", "two enzymes", "schwarz 2005", "ribbe 2009", "2009 .", "cofactor moco", "moco is", "is needed by", "needed by three", "by three enzymes", "three enzymes in", "enzymes in humans:", "in humans: sulfite", "humans: sulfite oxidase", "oxidase xanthine", "xanthine oxidase and", "oxidase and aldehyde", "and aldehyde oxidase.", "aldehyde oxidase. the", "oxidase. the pathway", "the pathway of", "pathway of its", "of its synthesis", "its synthesis is", "synthesis is so", "is so conserved", "so conserved that", "conserved that plants", "that plants and", "plants and bacteria", "and bacteria can", "bacteria can readily", "can readily use", "readily use human", "use human enzymes.", "human enzymes. bacteria", "bacteria however", "however diverge", "diverge after the", "after the first", "the first three", "first three steps", "three steps from", "steps from this", "from this path", "this path and", "path and their", "and their final", "their final moco", "final moco differs", "moco differs from", "differs from that", "from that of", "that of the", "of the eukaryotes.", "the eukaryotes. plants", "eukaryotes. plants and", "plants and animals", "and animals have", "animals have also", "have also developed", "also developed a", "developed a refinement", "a refinement of", "refinement of their", "of their moco", "their moco which", "moco which is", "which is needed", "is needed for", "needed for the", "for the function", "the function of", "function of their", "of their xanthine", "their xanthine and", "xanthine and aldehyde", "and aldehyde oxidases.", "aldehyde oxidases. this", "oxidases. this means", "means in", "in humans we", "humans we find", "we find sulfurated", "find sulfurated instead", "sulfurated instead of", "instead of 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human", "readily use human enzymes.", "use human enzymes. bacteria", "enzymes. bacteria however", "however diverge after", "diverge after the first", "after the first three", "the first three steps", "first three steps from", "three steps from this", "steps from this path", "from this path and", "this path and their", "path and their final", "and their final moco", "their final moco differs", "final moco differs from", "moco differs from that", "differs from that of", "from that of the", "that of the eukaryotes.", "of the eukaryotes. plants", "the eukaryotes. plants and", "eukaryotes. plants and animals", "plants and animals have", "and animals have also", "animals have also developed", "have also developed a", "also developed a refinement", "developed a refinement of", "a refinement of their", "refinement of their moco", "of their moco which", "their moco which is", "moco which is needed", "which is needed for", "is needed for the", "needed for the function", "for the function of", "the function of their", "function of their xanthine", "of their xanthine and", "their xanthine and aldehyde", "xanthine and aldehyde oxidases.", "and aldehyde oxidases. this", "aldehyde oxidases. this means", "this means in", "means in humans", "in humans we find", "humans we find sulfurated", "we find sulfurated instead", "find sulfurated instead of", "sulfurated instead of desulfurated", "instead of desulfurated molybdenum", "of desulfurated molybdenum cofactor", "desulfurated molybdenum cofactor on", "molybdenum cofactor on these", "cofactor on these two", "on these two enzymes", "two enzymes schwarz", "enzymes schwarz 2005", "schwarz 2005 schwarz", "mendel ribbe 2009", "cofactor moco is", "moco is needed by", "is needed by three enzymes", "needed by three enzymes in", "by three enzymes in humans:", "three enzymes in humans: sulfite", "enzymes in humans: sulfite oxidase", "humans: sulfite oxidase xanthine", "sulfite oxidase xanthine oxidase", "oxidase xanthine oxidase and", "xanthine oxidase and aldehyde oxidase.", "oxidase and aldehyde oxidase. the", "and aldehyde oxidase. the pathway", "aldehyde oxidase. the pathway of", "oxidase. the pathway of its", "the pathway of its synthesis", "pathway of its synthesis is", "of its synthesis is so", "its synthesis is so conserved", "synthesis is so conserved that", "is so conserved that plants", "so conserved that plants and", "conserved that plants and bacteria", "that plants and bacteria can", "plants and bacteria can readily", "and bacteria can readily use", "bacteria can readily use human", "can readily use human enzymes.", "readily use human enzymes. bacteria", "human enzymes. bacteria however", "bacteria however diverge", "however diverge after the", "diverge after the first three", "after the first three steps", "the first three steps from", "first three steps from this", "three steps from this path", "steps from this path and", "from this path and their", "this path and their final", "path and their final moco", "and their final moco differs", "their final moco differs from", "final moco differs from that", "moco differs from that of", "differs from that of the", "from that of the eukaryotes.", "that of the eukaryotes. plants", "of the eukaryotes. plants and", "the eukaryotes. plants and animals", "eukaryotes. plants and animals have", "plants and animals have also", "and animals have also developed", "animals have also developed a", "have also developed a refinement", "also developed a refinement of", "developed a refinement of their", "a refinement of their moco", "refinement of their moco which", "of their moco which is", "their moco which is needed", "moco which is needed for", "which is needed for the", "is needed for the function", "needed for the function of", "for the function of their", "the function of their xanthine", "function of their xanthine and", "of their xanthine and aldehyde", "their xanthine and aldehyde oxidases.", "xanthine and aldehyde oxidases. this", "and aldehyde oxidases. this means", "oxidases. this means in", "this means in humans", "means in humans we", "in humans we find sulfurated", "humans we find sulfurated instead", "we find sulfurated instead of", "find sulfurated instead of desulfurated", "sulfurated instead of desulfurated molybdenum", "instead of desulfurated molybdenum cofactor", "of desulfurated molybdenum cofactor on", "desulfurated molybdenum cofactor on these", "molybdenum cofactor on these two", "cofactor on these two enzymes", "these two enzymes schwarz", "two enzymes schwarz 2005", "2005 schwarz mendel", "schwarz mendel ribbe", "mendel ribbe 2009 ." ] }, { "record_id": "GLY_000594_1_1210", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9607240", "r hsa", "hsa 9607240", "r hsa 9607240" ] }, { "record_id": "GLY_000594_1_1210", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "flt3 signaling", "feline mcdonough", "mcdonough sarcoma", "sarcoma like", "like tyrosine", "tyrosine kinase", "also known", "known as", "as flk2", "fetal liver", "liver tyrosine", "kinase 2", "stk 1", "stem cell", "cell tyrosine", "kinase 1", "or cd135", "is a", "a member", "member of", "of the", "the class", "class iii", "iii receptor", "receptor tyrosine", "kinase family", "family involved", "involved in", "in the", "the differentiation", "proliferation and", "and survival", "survival of", "of hematopoietic", "hematopoietic progenitor", "progenitor cells", "cells and", "and of", "of dendritic", "dendritic cells.", "cells. upon", "upon flt3", "flt3 ligand", "the receptor", "receptor forms", "forms dimers", "dimers and", "and is", "is phosphorylated.", "phosphorylated. consequently", "adapter and", "and signaling", "signaling molecules", "molecules bind", "bind with", "with the", "the active", "active receptor", "receptor and", "and trigger", "trigger the", "the activation", "activation of", "of various", "various pathways", "pathways downstream", "downstream including", "including pi3k/akt", "pi3k/akt and", "and mapk", "mapk cascades", "grafone t", "t et", "et al.", "al. 2012", "2012 .", "feline mcdonough sarcoma", "mcdonough sarcoma like", "sarcoma like tyrosine", "like tyrosine kinase", "kinase flt3", "also known as", "known as flk2", "flk2 fetal", "fetal liver tyrosine", "liver tyrosine kinase", "tyrosine kinase 2", "1 stem", "stem cell tyrosine", "cell tyrosine kinase", "tyrosine kinase 1", "1 or", "cd135 is", "is a member", "a member of", "member of the", "of the class", "the class iii", "class iii receptor", "iii receptor tyrosine", "receptor tyrosine kinase", "tyrosine kinase family", "kinase family involved", "family involved in", "involved in the", "in the differentiation", "differentiation proliferation", "proliferation and survival", "and survival of", "survival of hematopoietic", "of hematopoietic progenitor", "hematopoietic progenitor cells", "progenitor cells and", "cells and of", "and of dendritic", "of dendritic cells.", "dendritic cells. upon", "cells. upon flt3", "upon flt3 ligand", "ligand fl", "fl binding", "binding the", "the receptor forms", "receptor forms dimers", "forms dimers and", "dimers and is", "and is phosphorylated.", "is phosphorylated. consequently", "consequently adapter", "adapter and signaling", "and signaling molecules", "signaling molecules bind", "molecules bind with", "bind with the", "with the active", "the active receptor", "active receptor and", "receptor and trigger", "and trigger the", "trigger the activation", "the activation of", "activation of various", "of various pathways", "various pathways downstream", "pathways downstream including", "downstream including pi3k/akt", "including pi3k/akt and", "pi3k/akt and mapk", "and mapk cascades", "cascades grafone", "grafone t et", "t et al.", "et al. 2012", "al. 2012 .", "feline mcdonough sarcoma like", "mcdonough sarcoma like tyrosine", "sarcoma like tyrosine kinase", "tyrosine kinase flt3", "flt3 also", "also known as flk2", "as flk2 fetal", "flk2 fetal liver", "fetal liver tyrosine kinase", "liver tyrosine kinase 2", "2 stk", "stk 1 stem", "1 stem cell", "stem cell tyrosine kinase", "cell tyrosine kinase 1", "kinase 1 or", "1 or cd135", "or cd135 is", "cd135 is a", "is a member of", "a member of the", "member of the class", "of the class iii", "the class iii receptor", "class iii receptor tyrosine", "iii receptor tyrosine kinase", "receptor tyrosine kinase family", "tyrosine kinase family involved", "kinase family involved in", "family involved in the", "involved in the differentiation", "the differentiation proliferation", "differentiation proliferation and", "proliferation and survival of", "and survival of hematopoietic", "survival of hematopoietic progenitor", "of hematopoietic progenitor cells", "hematopoietic progenitor cells and", "progenitor cells and of", "cells and of dendritic", "and of dendritic cells.", "of dendritic cells. upon", "dendritic cells. upon flt3", "cells. upon flt3 ligand", "flt3 ligand fl", "binding the receptor", "the receptor forms dimers", "receptor forms dimers and", "forms dimers and is", "dimers and is phosphorylated.", "and is phosphorylated. consequently", "phosphorylated. consequently adapter", "consequently adapter and", "adapter and signaling molecules", "and signaling molecules bind", "signaling molecules bind with", "molecules bind with the", "bind with the active", "with the active receptor", "the active receptor and", "active receptor and trigger", "receptor and trigger the", "and trigger the activation", "trigger the activation of", "the activation of various", "activation of various pathways", "of various pathways downstream", "various pathways downstream including", "pathways downstream including pi3k/akt", "downstream including pi3k/akt and", "including pi3k/akt and mapk", "pi3k/akt and mapk cascades", "mapk cascades grafone", "cascades grafone t", "grafone t et al.", "t et al. 2012", "et al. 2012 .", "feline mcdonough sarcoma like tyrosine", "mcdonough sarcoma like tyrosine kinase", "like tyrosine kinase flt3", "flt3 also known", "known as flk2 fetal", "as flk2 fetal liver", "flk2 fetal liver tyrosine", "fetal liver tyrosine kinase 2", "kinase 2 stk", "2 stk 1", "stk 1 stem cell", "1 stem cell tyrosine", "stem cell tyrosine kinase 1", "tyrosine kinase 1 or", "kinase 1 or cd135", "or cd135 is a", "cd135 is a member", "is a member of the", "a member of the class", "member of the class iii", "of the class iii receptor", "the class iii receptor tyrosine", "class iii receptor tyrosine kinase", "iii receptor tyrosine kinase family", "receptor tyrosine kinase family involved", "tyrosine kinase family involved in", "kinase family involved in the", "family involved in the differentiation", "in the differentiation proliferation", "the differentiation proliferation and", "differentiation proliferation and survival", "proliferation and survival of hematopoietic", "and survival of hematopoietic progenitor", "survival of hematopoietic progenitor cells", "of hematopoietic progenitor cells and", "hematopoietic progenitor cells and of", "progenitor cells and of dendritic", "cells and of dendritic cells.", "and of dendritic cells. upon", "of dendritic cells. upon flt3", "dendritic cells. upon flt3 ligand", "upon flt3 ligand fl", "ligand fl binding", "fl binding the", "binding the receptor forms", "the receptor forms dimers and", "receptor forms dimers and is", "forms dimers and is phosphorylated.", "dimers and is phosphorylated. consequently", "is phosphorylated. consequently adapter", "phosphorylated. consequently adapter and", "consequently adapter and signaling", "adapter and signaling molecules bind", "and signaling molecules bind with", "signaling molecules bind with the", "molecules bind with the active", "bind with the active receptor", "with the active receptor and", "the active receptor and trigger", "active receptor and trigger the", "receptor and trigger the activation", "and trigger the activation of", "trigger the activation of various", "the activation of various pathways", "activation of various pathways downstream", "of various pathways downstream including", "various pathways downstream including pi3k/akt", "pathways downstream including pi3k/akt and", "downstream including pi3k/akt and mapk", "including pi3k/akt and mapk cascades", "and mapk cascades grafone", "mapk cascades grafone t", "cascades grafone t et", "grafone t et al. 2012", "t et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1211", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9613354", "r hsa", "hsa 9613354", "r hsa 9613354" ] }, { "record_id": "GLY_000594_1_1211", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "triglycerides stored", "stored in", "in lipid", "lipid droplets", "droplets are", "are hydrolysed", "hydrolysed under", "under nutrient", "nutrient starvation", "starvation to", "to release", "release fatty", "fatty acids", "acids for", "for energy.", "energy. the", "the content", "content of", "of lipid", "droplets may", "may vary", "vary but", "but they", "they are", "are all", "all coated", "coated with", "with a", "a protective", "protective protein", "protein called", "called perilipin.", "perilipin. when", "when this", "this protein", "protein is", "is degraded", "droplets associate", "associate with", "with autophagic", "autophagic components", "components and", "and breakdown", "breakdown into", "into fatty", "ward c", "c et", "et al.", "al. 2016", "schulze r", "r j", "j et", "al. 2017", "2017 .", ". this", "this process", "process is", "is termed", "termed as", "as lipophagy", "singh r", "r et", "al. 2009", "2009 .", "triglycerides stored in", "stored in lipid", "in lipid droplets", "lipid droplets are", "droplets are hydrolysed", "are hydrolysed under", "hydrolysed under nutrient", "under nutrient starvation", "nutrient starvation to", "starvation to release", "to release fatty", "release fatty acids", "fatty acids for", "acids for energy.", "for energy. the", "energy. the content", "the content of", "content of lipid", "of lipid droplets", "lipid droplets may", "droplets may vary", "may vary but", "vary but they", "but they are", "they are all", "are all coated", "all coated with", "coated with a", "with a protective", "a protective protein", "protective protein called", "protein called perilipin.", "called perilipin. when", "perilipin. when this", "when this protein", "this protein is", "protein is degraded", "degraded lipid", "lipid droplets associate", "droplets associate with", "associate with autophagic", "with autophagic components", "autophagic components and", "components and breakdown", "and breakdown into", "breakdown into fatty", "into fatty acids", "acids ward", "ward c et", "c et al.", "et al. 2016", "2016 schulze", "schulze r j", "r j et", "j et al.", "et al. 2017", "al. 2017 .", "2017 . this", ". this process", "this process is", "process is termed", "is termed as", "termed as lipophagy", "lipophagy singh", "singh r et", "r et al.", "et al. 2009", "al. 2009 .", "triglycerides stored in lipid", "stored in lipid droplets", "in lipid droplets are", "lipid droplets are hydrolysed", "droplets are hydrolysed under", "are hydrolysed under nutrient", "hydrolysed under nutrient starvation", "under nutrient starvation to", "nutrient starvation to release", "starvation to release fatty", "to release fatty acids", "release fatty acids for", "fatty acids for energy.", "acids for energy. the", "for energy. the content", "energy. the content of", "the content of lipid", "content of lipid droplets", "of lipid droplets may", "lipid droplets may vary", "droplets may vary but", "may vary but they", "vary but they are", "but they are all", "they are all coated", "are all coated with", "all coated with a", "coated with a protective", "with a protective protein", "a protective protein called", "protective protein called perilipin.", "protein called perilipin. when", "called perilipin. when this", "perilipin. when this protein", "when this protein is", "this protein is degraded", "is degraded lipid", "degraded lipid droplets", "lipid droplets associate with", "droplets associate with autophagic", "associate with autophagic components", "with autophagic components and", "autophagic components and breakdown", "components and breakdown into", "and breakdown into fatty", "breakdown into fatty acids", "fatty acids ward", "acids ward c", "ward c et al.", "c et al. 2016", "al. 2016 schulze", "2016 schulze r", "schulze r j et", "r j et al.", "j et al. 2017", "et al. 2017 .", "al. 2017 . this", "2017 . this process", ". this process is", "this process is termed", "process is termed as", "is termed as lipophagy", "as lipophagy singh", "lipophagy singh r", "singh r et al.", "r et al. 2009", "et al. 2009 .", "triglycerides stored in lipid droplets", "stored in lipid droplets are", "in lipid droplets are hydrolysed", "lipid droplets are hydrolysed under", "droplets are hydrolysed under nutrient", "are hydrolysed under nutrient starvation", "hydrolysed under nutrient starvation to", "under nutrient starvation to release", "nutrient starvation to release fatty", "starvation to release fatty acids", "to release fatty acids for", "release fatty acids for energy.", "fatty acids for energy. the", "acids for energy. the content", "for energy. the content of", "energy. the content of lipid", "the content of lipid droplets", "content of lipid droplets may", "of lipid droplets may vary", "lipid droplets may vary but", "droplets may vary but they", "may vary but they are", "vary but they are all", "but they are all coated", "they are all coated with", "are all coated with a", "all coated with a protective", "coated with a protective protein", "with a protective protein called", "a protective protein called perilipin.", "protective protein called perilipin. when", "protein called perilipin. when this", "called perilipin. when this protein", "perilipin. when this protein is", "when this protein is degraded", "protein is degraded lipid", "is degraded lipid droplets", "degraded lipid droplets associate", "lipid droplets associate with autophagic", "droplets associate with autophagic components", "associate with autophagic components and", "with autophagic components and breakdown", "autophagic components and breakdown into", "components and breakdown into fatty", "and breakdown into fatty acids", "into fatty acids ward", "fatty acids ward c", "acids ward c et", "ward c et al. 2016", "et al. 2016 schulze", "al. 2016 schulze r", "2016 schulze r j", "schulze r j et al.", "r j et al. 2017", "j et al. 2017 .", "et al. 2017 . this", "al. 2017 . this process", "2017 . this process is", ". this process is termed", "this process is termed as", "process is termed as lipophagy", "termed as lipophagy singh", "as lipophagy singh r", "lipophagy singh r et", "singh r et al. 2009", "r et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1212", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9613829", "r hsa", "hsa 9613829", "r hsa 9613829" ] }, { "record_id": "GLY_000594_1_1212", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "chaperone mediated", "mediated autophagy", "chaperone mediated autophagy", "in contrary", "contrary to", "to the", "the vesicle", "vesicle mediated", "mediated macroautophagy", "the chaperone", "mediated mechanism", "mechanism of", "of autophagy", "autophagy selectively", "selectively targets", "targets individual", "individual proteins", "proteins to", "the lysosome", "lysosome for", "for degradation.", "degradation. chaperones", "chaperones bind", "bind intracellular", "intracellular proteins", "proteins based", "based on", "on recognition", "recognition motifs", "motifs and", "and transports", "transports them", "them from", "from the", 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"on recognition motifs", "recognition motifs and", "motifs and transports", "and transports them", "transports them from", "them from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the lysosomal", "the lysosomal membrane.", "lysosomal membrane. subsequently", "subsequently the", "the protein is", "protein is translocated", "is translocated into", "translocated into the", "into the lumen", "the lumen for", "lumen for digestion", "digestion cuervo", "cuervo a m", "a m et", "m et al.", "et al. 2014", "2014 kaushik", "kaushik s et", "s et al.", "et al. 2018", "al. 2018 .", "in contrary to the", "contrary to the vesicle", "to the vesicle mediated", "the vesicle mediated macroautophagy", "mediated macroautophagy the", "macroautophagy the chaperone", "the chaperone mediated mechanism", "chaperone mediated mechanism of", "mediated mechanism of autophagy", "mechanism of autophagy selectively", "of autophagy selectively targets", "autophagy selectively targets individual", "selectively targets individual proteins", "targets individual proteins to", "individual proteins to the", "proteins to the lysosome", "to the lysosome for", "the lysosome for degradation.", "lysosome for degradation. chaperones", "for degradation. chaperones bind", "degradation. chaperones bind intracellular", "chaperones bind intracellular proteins", "bind intracellular proteins based", "intracellular proteins based on", "proteins based on recognition", "based on recognition motifs", "on recognition motifs and", "recognition motifs and transports", "motifs and transports them", "and transports them from", "transports them from the", "them from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the lysosomal", "to the lysosomal membrane.", "the lysosomal membrane. subsequently", "membrane. subsequently the", "subsequently the protein", "the protein is translocated", "protein is translocated into", "is translocated into the", "translocated into the lumen", "into the lumen for", "the lumen for digestion", "for digestion cuervo", "digestion cuervo a", "cuervo a m et", "a m et al.", "m et al. 2014", "al. 2014 kaushik", "2014 kaushik s", "kaushik s et al.", "s et al. 2018", "et al. 2018 .", "in contrary to the vesicle", "contrary to the vesicle mediated", "to the vesicle mediated macroautophagy", "vesicle mediated macroautophagy the", "mediated macroautophagy the chaperone", "macroautophagy the chaperone mediated", "the chaperone mediated mechanism of", "chaperone mediated mechanism of autophagy", "mediated mechanism of autophagy selectively", "mechanism of autophagy selectively targets", "of autophagy selectively targets individual", "autophagy selectively targets individual proteins", "selectively targets individual proteins to", "targets individual proteins to the", "individual proteins to the lysosome", "proteins to the lysosome for", "to the lysosome for degradation.", "the lysosome for degradation. chaperones", "lysosome for degradation. chaperones bind", "for degradation. chaperones bind intracellular", "degradation. chaperones bind intracellular proteins", "chaperones bind intracellular proteins based", "bind intracellular proteins based on", "intracellular proteins based on recognition", "proteins based on recognition motifs", "based on recognition motifs and", "on recognition motifs and transports", "recognition motifs and transports them", "motifs and transports them from", "and transports them from the", "transports them from the cytosol", "them from the cytosol to", "from the cytosol to the", "the cytosol to the lysosomal", "cytosol to the lysosomal membrane.", "to the lysosomal membrane. subsequently", "lysosomal membrane. subsequently the", "membrane. subsequently the protein", "subsequently the protein is", "the protein is translocated into", "protein is translocated into the", "is translocated into the lumen", "translocated into the lumen for", "into the lumen for digestion", "lumen for digestion cuervo", "for digestion cuervo a", "digestion cuervo a m", "cuervo a m et al.", "a m et al. 2014", "et al. 2014 kaushik", "al. 2014 kaushik s", "2014 kaushik s et", "kaushik s et al. 2018", "s et al. 2018 ." ] }, { "record_id": "GLY_000594_1_1213", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9614657", "r hsa", "hsa 9614657", "r hsa 9614657" ] }, { "record_id": "GLY_000594_1_1213", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "foxo mediated", "mediated transcription", "transcription of", "of cell", "cell death", "death genes", "foxo mediated transcription", "mediated transcription of", "transcription of cell", "of cell death", "cell death genes", "foxo mediated transcription of", "mediated transcription of cell", "transcription of cell death", "of cell death genes", "foxo mediated transcription of cell", "mediated transcription of cell death", "transcription of cell death genes", "foxo transcription", "transcription factors", "factors promote", "promote expression", "expression of", "of several", "several pro", "pro apoptotic", "apoptotic genes", "such as", "as faslg", "brunet et", "et al.", "al. 1999", "ciechomska et", "al. 2003", "chen et", "al. 2013", "li et", "al. 2015", "mei et", "al. 2009", "sengupta et", "al. 2011", "gilley et", "urbich et", "al. 2005", "chuang et", "al. 2007", "hughes et", "wang et", "al. 2016", "tang et", "al. 2002", "fernandez de", "de mattos", "mattos et", "al. 2004", "shore et", "al. 2006", "and bbc3", "dudgeon et", "al. 2010", "liu et", "wu et", "al. 2017", "fitzwalter et", "al. 2018", "2018 .", ". foxo", "mediated induction", "induction of", "genes is", "is important", "important during", "during development", "for example", "example during", "during nervous", "nervous system", "system development", "where foxo", "foxo promotes", "promotes neuronal", "neuronal death", "death upon", "upon ngf", "ngf withdrawal", "and also", "also contributes", "contributes to", "to the", "the tumor", "tumor suppressive", "suppressive role", "role of", "of foxo", "foxo factors", "arimoto ishida", "ishida et", "2004 .", ". foxo1", "foxo1 transcriptional", "transcriptional activity", "activity is", "is implicated", "implicated in", "in the", "the cell", "death of", "of enteric", "enteric nervous", "precursors. ret", "ret signaling", "which activates", "activates pi3k/akt", "pi3k/akt signaling", "leading to", "to inhibition", "inhibition of", "ensures survival", "survival of", "of ens", "ens precursors", "srinivasan et", "2005 .
              transcription", ".
              transcription of", "of the", "the stk11", "encoding serine/threonine", "serine/threonine protein", "protein kinase", "kinase stk11", "also known", "known as", "as liver", "liver kinase", "kinase b1", "which regulates", "regulates diverse", "diverse cellular", "cellular processes", "including apoptosis", "is directly", "directly stimulated", "stimulated by", "by foxo3", "foxo3 and", "and foxo4", "lutzner et", "al. 2012", "2012 .", "foxo transcription factors", "transcription factors promote", "factors promote expression", "promote expression of", "expression of several", "of several pro", "several pro apoptotic", "pro apoptotic genes", "genes such", "such as faslg", "faslg brunet", "brunet et al.", "et al. 1999", "1999 ciechomska", "ciechomska et al.", "et al. 2003", "2003 chen", "chen et al.", "et al. 2013", "2013 li", "li et al.", "et al. 2015", "pink1 mei", "mei et al.", "et al. 2009", "2009 sengupta", "sengupta et al.", "et al. 2011", "bcl2l11 bim", "gilley et al.", "2003 urbich", "urbich et al.", "et al. 2005", "2005 chuang", "chuang et al.", "et al. 2007", "2007 hughes", "hughes et al.", "2011 chen", "2013 wang", "wang et al.", "et al. 2016", "bcl6 tang", "tang et al.", "et al. 2002", "2002 fernandez", "fernandez de mattos", "de mattos et", "mattos et al.", "et al. 2004", "2004 shore", "shore et al.", "et al. 2006", "2006 and", "bbc3 puma", "dudgeon et al.", "et al. 2010", "2010 hughes", "2011 liu", "liu et al.", "2015 wu", "wu et al.", "2016 liu", "et al. 2017", "2017 fitzwalter", "fitzwalter et al.", "et al. 2018", "al. 2018 .", "2018 . foxo", ". foxo mediated", "foxo mediated induction", "mediated induction of", "induction of cell", "death genes is", "genes is important", "is important during", "important during development", "development for", "for example during", "example during nervous", "during nervous system", "nervous system development", "development where", "where foxo promotes", "foxo promotes neuronal", "promotes neuronal death", "neuronal death upon", "death upon ngf", "upon ngf withdrawal", "withdrawal gilley", "and also contributes", "also contributes to", "contributes to the", "to the tumor", "the tumor suppressive", "tumor suppressive role", "suppressive role of", "role of foxo", "of foxo factors", "factors arimoto", "arimoto ishida et", "ishida et al.", "al. 2004 .", "2004 . foxo1", ". foxo1 transcriptional", "foxo1 transcriptional activity", "transcriptional activity is", "activity is implicated", "is implicated in", "implicated in the", "in the cell", "the cell death", "cell death of", "death of enteric", "of enteric nervous", "enteric nervous system", "system ens", "ens precursors.", "precursors. ret signaling", "signaling which", "which activates pi3k/akt", "activates pi3k/akt signaling", "signaling leading", "leading to inhibition", "to inhibition of", "inhibition of foxo", "of foxo mediated", "transcription ensures", "ensures survival of", "survival of ens", "of ens precursors", "precursors srinivasan", "srinivasan et al.", "al. 2005 .
              transcription", "2005 .
              transcription of", ".
              transcription of the", "of the stk11", "stk11 lkb1", "lkb1 gene", "gene encoding", "encoding serine/threonine protein", "serine/threonine protein kinase", "protein kinase stk11", "stk11 also", "also known as", "known as liver", "as liver kinase", "liver kinase b1", "which regulates diverse", "regulates diverse cellular", "diverse cellular processes", "processes including", "apoptosis is", "is directly stimulated", "directly stimulated by", "stimulated by foxo3", "by foxo3 and", "foxo3 and foxo4", "foxo4 lutzner", "lutzner et al.", "et al. 2012", "al. 2012 .", "foxo transcription factors promote", "transcription factors promote expression", "factors promote expression of", "promote expression of several", "expression of several pro", "of several pro apoptotic", "several pro apoptotic genes", "apoptotic genes such", "genes such as", "as faslg brunet", "faslg brunet et", "brunet et al. 1999", "al. 1999 ciechomska", "1999 ciechomska et", "ciechomska et al. 2003", "al. 2003 chen", "2003 chen et", "chen et al. 2013", "al. 2013 li", "2013 li et", "li et al. 2015", "2015 pink1", "pink1 mei et", "mei et al. 2009", "al. 2009 sengupta", "2009 sengupta et", "sengupta et al. 2011", "2011 bcl2l11", "bim gilley", "gilley et al. 2003", "al. 2003 urbich", "2003 urbich et", "urbich et al. 2005", "al. 2005 chuang", "2005 chuang et", "chuang et al. 2007", "al. 2007 hughes", "2007 hughes et", "hughes et al. 2011", "al. 2011 chen", "2011 chen et", "al. 2013 wang", "2013 wang et", "wang et al. 2016", "2016 bcl6", "bcl6 tang et", "tang et al. 2002", "al. 2002 fernandez", "2002 fernandez de", "fernandez de mattos et", "de mattos et al.", "mattos et al. 2004", "al. 2004 shore", "2004 shore et", "shore et al. 2006", "al. 2006 and", "2006 and bbc3", "and bbc3 puma", "puma dudgeon", "dudgeon et al. 2010", "al. 2010 hughes", "2010 hughes et", "al. 2011 liu", "2011 liu et", "liu et al. 2015", "al. 2015 wu", "2015 wu et", "wu et al. 2016", "al. 2016 liu", "2016 liu et", "liu et al. 2017", "al. 2017 fitzwalter", "2017 fitzwalter et", "fitzwalter et al. 2018", "et al. 2018 .", "al. 2018 . foxo", "2018 . foxo mediated", ". foxo mediated induction", "foxo mediated induction of", "mediated induction of cell", "induction of cell death", "cell death genes is", "death genes is important", "genes is important during", "is important during development", "during development for", "development for example", "for example during nervous", "example during nervous system", "during nervous system development", "system development where", "development where foxo", "where foxo promotes neuronal", "foxo promotes neuronal death", "promotes neuronal death upon", "neuronal death upon ngf", "death upon ngf withdrawal", "ngf withdrawal gilley", "withdrawal gilley et", "2003 and", "and also contributes to", "also contributes to the", "contributes to the tumor", "to the tumor suppressive", "the tumor suppressive role", "tumor suppressive role of", "suppressive role of foxo", "role of foxo factors", "foxo factors arimoto", "factors arimoto ishida", "arimoto ishida et al.", "ishida et al. 2004", "et al. 2004 .", "al. 2004 . foxo1", "2004 . foxo1 transcriptional", ". foxo1 transcriptional activity", "foxo1 transcriptional activity is", "transcriptional activity is implicated", "activity is implicated in", "is implicated in the", "implicated in the cell", "in the cell death", "the cell death of", "cell death of enteric", "death of enteric nervous", "of enteric nervous system", "nervous system ens", "ens precursors. ret", "ret signaling which", "signaling which activates", "which activates pi3k/akt signaling", "pi3k/akt signaling leading", "signaling leading to", "leading to inhibition of", "to inhibition of foxo", "inhibition of foxo mediated", "of foxo mediated transcription", "mediated transcription ensures", "transcription ensures survival", "ensures survival of ens", "survival of ens precursors", "ens precursors srinivasan", "precursors srinivasan et", "srinivasan et al. 2005", "et al. 2005 .
              transcription", "al. 2005 .
              transcription of", "2005 .
              transcription of the", ".
              transcription of the stk11", "the stk11 lkb1", "gene encoding serine/threonine", "encoding serine/threonine protein kinase", "serine/threonine protein kinase stk11", "kinase stk11 also", "stk11 also known", "also known as liver", "known as liver kinase", "as liver kinase b1", "b1 which", "which regulates diverse cellular", "regulates diverse cellular processes", "cellular processes including", "processes including apoptosis", "including apoptosis is", "apoptosis is directly", "is directly stimulated by", "directly stimulated by foxo3", "stimulated by foxo3 and", "by foxo3 and foxo4", "and foxo4 lutzner", "foxo4 lutzner et", "lutzner et al. 2012", "et al. 2012 .", "foxo transcription factors promote expression", "transcription factors promote expression of", "factors promote expression of several", "promote expression of several pro", "expression of several pro apoptotic", "of several pro apoptotic genes", "pro apoptotic genes such", "apoptotic genes such as", "genes such as faslg", "such as faslg brunet", "as faslg brunet et", "faslg brunet et al.", "et al. 1999 ciechomska", "al. 1999 ciechomska et", "1999 ciechomska et al.", "et al. 2003 chen", "al. 2003 chen et", "2003 chen et al.", "et al. 2013 li", "al. 2013 li et", "2013 li et al.", "al. 2015 pink1", "pink1 mei et al.", "et al. 2009 sengupta", "al. 2009 sengupta et", "2009 sengupta et al.", "al. 2011 bcl2l11", "bim gilley et", "et al. 2003 urbich", "al. 2003 urbich et", "2003 urbich et al.", "et al. 2005 chuang", "al. 2005 chuang et", "2005 chuang et al.", "et al. 2007 hughes", "al. 2007 hughes et", "2007 hughes et al.", "et al. 2011 chen", "al. 2011 chen et", "2011 chen et al.", "et al. 2013 wang", "al. 2013 wang et", "2013 wang et al.", "al. 2016 bcl6", "bcl6 tang et al.", "et al. 2002 fernandez", "al. 2002 fernandez de", "2002 fernandez de mattos", "fernandez de mattos et al.", "de mattos et al. 2004", "et al. 2004 shore", "al. 2004 shore et", "2004 shore et al.", "et al. 2006 and", "al. 2006 and bbc3", "puma dudgeon et", "et al. 2010 hughes", "al. 2010 hughes et", "2010 hughes et al.", "et al. 2011 liu", "al. 2011 liu et", "2011 liu et al.", "et al. 2015 wu", "al. 2015 wu et", "2015 wu et al.", "et al. 2016 liu", "al. 2016 liu et", "2016 liu et al.", "et al. 2017 fitzwalter", "al. 2017 fitzwalter et", "2017 fitzwalter et al.", "fitzwalter et al. 2018 .", "et al. 2018 . foxo", "al. 2018 . foxo mediated", "2018 . foxo mediated induction", ". foxo mediated induction of", "foxo mediated induction of cell", "mediated induction of cell death", "induction of cell death genes", "of cell death genes is", "cell death genes is important", "death genes is important during", "genes is important during development", "important during development for", "during development for example", "development for example during", "for example during nervous system", "example during nervous system development", "nervous system development where", "system development where foxo", "development where foxo promotes", "where foxo promotes neuronal death", "foxo promotes neuronal death upon", "promotes neuronal death upon ngf", "neuronal death upon ngf withdrawal", "upon ngf withdrawal gilley", "ngf withdrawal gilley et", "withdrawal gilley et al.", "al. 2003 and", "2003 and also", "and also contributes to the", "also contributes to the tumor", "contributes to the tumor suppressive", "to the tumor suppressive role", "the tumor suppressive role of", "tumor suppressive role of foxo", "suppressive role of foxo factors", "of foxo factors arimoto", "foxo factors arimoto ishida", "factors arimoto ishida et", "arimoto ishida et al. 2004", "ishida et al. 2004 .", "et al. 2004 . foxo1", "al. 2004 . foxo1 transcriptional", "2004 . foxo1 transcriptional activity", ". foxo1 transcriptional activity is", "foxo1 transcriptional activity is implicated", "transcriptional activity is implicated in", "activity is implicated in the", "is implicated in the cell", "implicated in the cell death", "in the cell death of", "the cell death of enteric", "cell death of enteric nervous", "death of enteric nervous system", "enteric nervous system ens", "system ens precursors.", "ens precursors. ret signaling", "precursors. ret signaling which", "ret signaling which activates", "signaling which activates pi3k/akt", "activates pi3k/akt signaling leading", "pi3k/akt signaling leading to", "signaling leading to inhibition", "leading to inhibition of foxo", "to inhibition of foxo mediated", "inhibition of foxo mediated transcription", "foxo mediated transcription ensures", "mediated transcription ensures survival", "transcription ensures survival of", "ensures survival of ens precursors", "of ens precursors srinivasan", "ens precursors srinivasan et", "precursors srinivasan et al.", "srinivasan et al. 2005 .
              transcription", "et al. 2005 .
              transcription of", "al. 2005 .
              transcription of the", "2005 .
              transcription of the stk11", "of the stk11 lkb1", "stk11 lkb1 gene", "lkb1 gene encoding", "gene encoding serine/threonine protein", "encoding serine/threonine protein kinase stk11", "protein kinase stk11 also", "kinase stk11 also known", "stk11 also known as", "also known as liver kinase", "known as liver kinase b1", "kinase b1 which", "b1 which regulates", "which regulates diverse cellular processes", "diverse cellular processes including", "cellular processes including apoptosis", "including apoptosis is directly", "apoptosis is directly stimulated", "is directly stimulated by foxo3", "directly stimulated by foxo3 and", "stimulated by foxo3 and foxo4", "foxo3 and foxo4 lutzner", "and foxo4 lutzner et", "foxo4 lutzner et al.", "lutzner et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1214", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9616222", "r hsa", "hsa 9616222", "r hsa 9616222" ] }, { "record_id": "GLY_000594_1_1214", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation of", "of granulopoiesis", "transcriptional regulation of", "regulation of granulopoiesis", "transcriptional regulation of granulopoiesis", "neutrophilic granulocytes", "hereafter called", "called granulocytes", "are distinguished", "distinguished by", "by multilobulated", "multilobulated nuclei", "nuclei and", "and presence", "presence of", "of cytoplasmic", "cytoplasmic granules", "granules containing", "containing antipathogenic", "antipathogenic proteins", "reviewed in", "in cowland", "cowland and", "and borregaard", "borregaard 2016", "yin and", "and heit", "heit 2018", "2018 .", ". granulocytes", "granulocytes comprise", "comprise eosinophils", "mast cells", "and neutrophils", "all of", "of which", "which are", "are ultimately", "ultimately derived", "derived from", "from hemopoietic", "hemopoietic stem", "stem cells", "a self", "self renewing", "renewing population", "population of", "of stem", "cells located", "located in", "in the", "the bone", "bone marrow.", "marrow. a", "a portion", "portion of", "of hscs", "hscs exit", "exit self", "renewing proliferation", "proliferation and", "and differentiate", "differentiate to", "to form", "form multipotent", "multipotent progenitors", "mpps .", ". mpps", "mpps then", "then differentiate", "form common", "common myeloid", "myeloid progenitors", "as well", "well as", "as the", "the erythrocyte", "erythrocyte lineage.", "lineage. cmps", "cmps further", "further differentiate", "differentiate into", "into granulocyte", "granulocyte monocyte", "monocyte progenitors", "which can", "can then", "into monocytes", "monocytes or", "or any", "any of", "of the", "the types", "types of", "of granulocytes", "in fiedler", "fiedler and", "and brunner", "brunner 2012", "2012 .", "granulocytes are", "are the", "the most", "most abundant", "abundant leukocytes", "leukocytes in", "in peripheral", "peripheral blood.
              for", "blood.
              for early", "early granulopoiesis", "granulopoiesis the", "the cebpa", "and myb", "myb transcription", "transcription factors", "factors are", "are essential.", "essential. cebpe", "and hoxa10", "hoxa10 transcription", "factors initiate", "initiate terminal", "terminal neutrophil", "neutrophil differentiation.
              initially", "runx1 activates", "activates spi1", "which is", "is believed", "believed to", "to be", "be the", "the key", "key transcription", "transcription factor", "factor driving", "driving the", "the formation", "formation of", "of mpps", "mpps and", "and cmps", "in friedman", "friedman 2007", ". spi1", "in turn", "activates expression", "expression of", "of cebpa", "an indispensable", "indispensable transcription", "factor for", "for granulopoiesis", "granulopoiesis especially", "especially important", "important in", "the transition", "transition from", "from cmp", "cmp to", "to gmp", "inferred from", "from mouse", "mouse homologs", "homologs in", "in wilson", "wilson et", "et al.", "al. 2010", "guo et", "al. 2012", "al. 2014", "cooper et", "al. 2015", "2015 .", ". cebpa", "activates the", "the expression", "of several", "several transcription", "factors and", "and receptors", "receptors characteristic", "characteristic of", "including cebpa", "loke et", "al. 2018", "and inferred", "in wang", "wang and", "and friedman", "friedman 2002", "friedman et", "al. 2003", "in lidonnici", "lidonnici et", "federzoni et", "in zhang", "zhang et", "al. 1998", "and csf3r", "smith et", "al. 1996", "1996 .", ". importantly", "cebpa dimers", "dimers repress", "repress transcription", "transcription of", "of myc", "c myc", "johansen et", "al. 2001", "in slomiany", "slomiany et", "al. 2000", "porse et", "2001 .", "cebpa binds", "binds cdk2", "cdk2 and", "and cdk4", "wang et", "which inhibits", "inhibits their", "their kinase", "kinase activity", "activity by", "by disrupting", "disrupting their", "their association", "association with", "with cyclins", "cyclins thereby", "thereby limiting", "limiting proliferation", "and favoring", "favoring differentiation", "differentiation of", "of granulocyte", "granulocyte progenitors", "progenitors during", "during regular", "\\steady state\\", "friedman 2015", ". the", "the transcription", "factor gfi1", "gfi1 regulates", "regulates g", "g csf", "csf signaling", "signaling and", "and neutrophil", "neutrophil development", "development through", "through the", "the ras", "ras activator", "activator rasgrp1", "de la", "la luz", "luz sierra", "sierra et", "2010 .
              inhibitors", ".
              inhibitors of", "of dna", "dna binding", "proteins id1", "id1 and", "and id2", "id2 regulate", "regulate granulopoiesis", "granulopoiesis and", "and eosinophil", "eosinophil production", "production such", "such that", "that id1", "id1 induces", "induces neutrophil", "development and", "and inhibits", "inhibits eosinophil", "eosinophil differentiation", "whereas id2", "id2 induces", "induces both", "both eosinophil", "eosinophil and", "buitenhuis et", "al. 2005", "skokowa et", "al. 2009", "2009 .
              major", ".
              major infection", "infection activates", "activates emergency", "emergency granulopoiesis", "in manz", "manz and", "and boettcher", "boettcher 2014", "hirai et", "the production", "production of", "of large", "large numbers", "numbers of", "granulocytes in", "in a", "a relatively", "relatively short", "short period", "period of", "of time.", "time. emergency", "granulopoiesis is", "is activated", "activated by", "by cytokines", "gm csf", "and especially", "especially csf3", "in panopoulos", "panopoulos and", "and watowich", "watowich 2008", "liongue et", "which bind", "bind receptors", "csf2r and", "resulting in", "in expression", "of cebpb", "which interferes", "interferes with", "with repression", "repression of", "myc by", "by cebpa", "and represses", "represses myc", "myc less", "less than", "than cebpa", "cebpa does", "al. 2006", "leading to", "to proliferation", "proliferation of", "progenitors prior", "prior to", "to final", "final differentiation.both", "emergency and", "and steady", "steady state", "state granulopoiesis", "granulopoiesis are", "are regulated", "regulated by", "by direct", "direct interaction", "interaction of", "or cebpb", "proteins with", "with nad+", "nad+ dependent", "dependent protein", "protein deacetylases", "sirt1 and", "and sirt2", "2009 .", ". g", "csf induces", "induces the", "the nad+", "nad+ generating", "generating enzyme", "nicotinamide phosphoribosyltransferase", "or pbef", "that in", "turn activates", "activates sirtuins", "2009 .
              gadd45a", ".
              gadd45a and", "and gadd45b", "gadd45b proteins", "proteins are", "are essential", "essential for", "for stress", "stress induced", "induced granulopoiesis", "and granulocyte", "granulocyte chemotaxis", "chemotaxis by", "by activation", "activation of", "of p38", "p38 kinase", "gupta et", "salerno et", ". shp2", "shp2 is", "is required", "required for", "for induction", "induction of", "cebpa expression", "expression and", "and granulopoiesis", "granulopoiesis in", "in response", "response to", "to csf3", "or other", "other cytokines", "cytokines independent", "independent of", "of shp2", "shp2 mediated", "mediated erk", "erk activation", "al. 2011", "2011 .
              transcription", ".
              transcription of", "of neutrophil", "neutrophil granule", "granule proteins", "e.g. elane", "that play", "play an", "an essential", "essential role", "role in", "in bacterial", "bacterial killing", "killing are", "by cebpe", "cebpe and", "and spi1", "gombart et", "nakajima et", "2006 .", ". runx1", "runx1 and", "and lef1", "lef1 also", "also regulate", "regulate elane", "mrna expression", "expression by", "by binding", "binding to", "to its", "its promoter", "li et", "2003 .", "granulocytes hereafter", "hereafter called granulocytes", "are distinguished by", "distinguished by multilobulated", "by multilobulated nuclei", "multilobulated nuclei and", "nuclei and presence", "and presence of", "presence of cytoplasmic", "of cytoplasmic granules", "cytoplasmic granules containing", "granules containing antipathogenic", "containing antipathogenic proteins", "proteins reviewed", "reviewed in cowland", "in cowland and", "cowland and borregaard", "and borregaard 2016", "2016 yin", "yin and heit", "and heit 2018", "heit 2018 .", "2018 . granulocytes", ". granulocytes comprise", "granulocytes comprise eosinophils", "eosinophils basophils", "basophils mast", "cells and", "neutrophils all", "all of which", "of which are", "which are ultimately", "are ultimately derived", "ultimately derived from", "derived from hemopoietic", "from hemopoietic stem", "hemopoietic stem cells", "cells hscs", "a self renewing", "self renewing population", "renewing population of", "population of stem", "of stem cells", "stem cells located", "cells located in", "located in the", "in the bone", "the bone marrow.", "bone marrow. a", "marrow. a portion", "a portion of", "portion of hscs", "of hscs exit", "hscs exit self", "exit self renewing", "self renewing proliferation", "renewing proliferation and", "proliferation and differentiate", "and differentiate to", "differentiate to form", "to form multipotent", "form multipotent progenitors", "progenitors mpps", "mpps . mpps", ". mpps then", "mpps then differentiate", "then differentiate to", "to form common", "form common myeloid", "common myeloid progenitors", "progenitors cmps", "cmps as", "as well as", "well as the", "as the erythrocyte", "the erythrocyte lineage.", "erythrocyte lineage. cmps", "lineage. cmps further", "cmps further differentiate", "further differentiate into", "differentiate into granulocyte", "into granulocyte monocyte", "granulocyte monocyte progenitors", "progenitors gmps", "gmps which", "which can then", "can then differentiate", "then differentiate into", "differentiate into monocytes", "into monocytes or", "monocytes or any", "or any of", "any of the", "of the types", "the types of", "types of granulocytes", "granulocytes reviewed", "reviewed in fiedler", "in fiedler and", "fiedler and brunner", "and brunner 2012", "brunner 2012 .", "2012 . granulocytes", ". granulocytes are", "granulocytes are the", "are the most", "the most abundant", "most abundant leukocytes", "abundant leukocytes in", "leukocytes in peripheral", "in peripheral blood.
              for", "peripheral blood.
              for early", "blood.
              for early granulopoiesis", "early granulopoiesis the", "granulopoiesis the cebpa", "cebpa spi1", "spi1 pu.1", "rar cbf", "cbf and", "and myb transcription", "myb transcription factors", "transcription factors are", "factors are essential.", "are essential. cebpe", "cebpe spi1", "spi1 sp1", "sp1 cdp", "cdp and", "and hoxa10 transcription", "hoxa10 transcription factors", "transcription factors initiate", "factors initiate terminal", "initiate terminal neutrophil", "terminal neutrophil differentiation.
              initially", "differentiation.
              initially runx1", "runx1 activates spi1", "which is believed", "is believed to", "believed to be", "to be the", "be the key", "the key transcription", "key transcription factor", "transcription factor driving", "factor driving the", "driving the formation", "the formation of", "formation of mpps", "of mpps and", "mpps and cmps", "cmps reviewed", "reviewed in friedman", "in friedman 2007", "2007 fiedler", "2012 . spi1", "spi1 in", "activates expression of", "expression of cebpa", "cebpa an", "an indispensable transcription", "indispensable transcription factor", "transcription factor for", "factor for granulopoiesis", "for granulopoiesis especially", "granulopoiesis especially important", "especially important in", "important in the", "in the transition", "the transition from", "transition from cmp", "from cmp to", "cmp to gmp", "gmp inferred", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in wilson", "in wilson et", "wilson et al.", "et al. 2010", "2010 guo", "guo et al.", "et al. 2012", "2012 guo", "et al. 2014", "2014 cooper", "cooper et al.", "et al. 2015", "al. 2015 .", "2015 . cebpa", "cebpa in", "activates the expression", "the expression of", "expression of several", "of several transcription", "several transcription factors", "transcription factors and", "factors and receptors", "and receptors characteristic", "receptors characteristic of", "characteristic of granulocytes", "granulocytes including", "cebpa autoregulation", "cebpe loke", "loke et al.", "et al. 2018", "2018 and", "and inferred from", "homologs in wang", "in wang and", "wang and friedman", "and friedman 2002", "2002 friedman", "friedman et al.", "et al. 2003", "gfi1 inferred", "homologs in lidonnici", "in lidonnici et", "lidonnici et al.", "klf5 federzoni", "federzoni et al.", "il6r inferred", "homologs in zhang", "in zhang et", "zhang et al.", "et al. 1998", "csf3r smith", "smith et al.", "et al. 1996", "al. 1996 .", "1996 . importantly", "importantly cebpa", "cebpa dimers repress", "dimers repress transcription", "repress transcription of", "transcription of myc", "myc c", "johansen et al.", "et al. 2001", "2001 and", "homologs in slomiany", "in slomiany et", "slomiany et al.", "et al. 2000", "2000 porse", "porse et al.", "al. 2001 .", "2001 . cebpa", ". cebpa binds", "cebpa binds cdk2", "binds cdk2 and", "cdk2 and cdk4", "cdk4 wang", "wang et al.", "2001 which", "which inhibits their", "inhibits their kinase", "their kinase activity", "kinase activity by", "activity by disrupting", "by disrupting their", "disrupting their association", "their association with", "association with cyclins", "with cyclins thereby", "cyclins thereby limiting", "thereby limiting proliferation", "limiting proliferation and", "proliferation and favoring", "and favoring differentiation", "favoring differentiation of", "differentiation of granulocyte", "of granulocyte progenitors", "granulocyte progenitors during", "progenitors during regular", "regular \\steady", "state\\ granulopoiesis", "granulopoiesis reviewed", "in friedman 2015", "friedman 2015 .", "2015 . the", ". the transcription", "the transcription factor", "transcription factor gfi1", "factor gfi1 regulates", "gfi1 regulates g", "regulates g csf", "g csf signaling", "csf signaling and", "signaling and neutrophil", "and neutrophil development", "neutrophil development through", "development through the", "through the ras", "the ras activator", "ras activator rasgrp1", "rasgrp1 de", "de la luz", "la luz sierra", "luz sierra et", "sierra et al.", "al. 2010 .
              inhibitors", "2010 .
              inhibitors of", ".
              inhibitors of dna", "of dna binding", "binding id", "id proteins", "proteins id1 and", "id1 and id2", "and id2 regulate", "id2 regulate granulopoiesis", "regulate granulopoiesis and", "granulopoiesis and eosinophil", "and eosinophil production", "eosinophil production such", "production such that", "such that id1", "that id1 induces", "id1 induces neutrophil", "induces neutrophil development", "neutrophil development and", "development and inhibits", "and inhibits eosinophil", "inhibits eosinophil differentiation", "differentiation whereas", "whereas id2 induces", "id2 induces both", "induces both eosinophil", "both eosinophil and", "eosinophil and neutrophil", "development buitenhuis", "buitenhuis et al.", "et al. 2005", "2005 skokowa", "skokowa et al.", "et al. 2009", "al. 2009 .
              major", "2009 .
              major infection", ".
              major infection activates", "infection activates emergency", "activates emergency granulopoiesis", "reviewed in manz", "in manz and", "manz and boettcher", "and boettcher 2014", "2014 hirai", "hirai et al.", "the production of", "production of large", "of large numbers", "large numbers of", "numbers of granulocytes", "of granulocytes in", "granulocytes in a", "in a relatively", "a relatively short", "relatively short period", "short period of", "period of time.", "of time. emergency", "time. emergency granulopoiesis", "emergency granulopoiesis is", "granulopoiesis is activated", "is activated by", "activated by cytokines", "cytokines csf2", "csf2 gm", "csf and", "and especially csf3", "csf3 g", "csf reviewed", "reviewed in panopoulos", "in panopoulos and", "panopoulos and watowich", "and watowich 2008", "2008 liongue", "liongue et al.", "2009 which", "which bind receptors", "receptors csf2r", "csf2r and csf3r", "csf3r respectively", "respectively resulting", "resulting in expression", "in expression of", "expression of cebpb", "cebpb which", "which interferes with", "interferes with repression", "with repression of", "repression of myc", "of myc by", "myc by cebpa", "cebpa inferred", "2010 and", "and represses myc", "represses myc less", "myc less than", "less than cebpa", "than cebpa does", "does hirai", "et al. 2006", "leading to proliferation", "to proliferation of", "proliferation of granulocyte", "granulocyte progenitors prior", "progenitors prior to", "prior to final", "to final differentiation.both", "differentiation.both emergency", "emergency and steady", "and steady state", "steady state granulopoiesis", "state granulopoiesis are", "granulopoiesis are regulated", "are regulated by", "regulated by direct", "by direct interaction", "direct interaction of", "interaction of cebpa", "cebpa steady", "state or", "cebpb emergency", "emergency proteins", "proteins with nad+", "with nad+ dependent", "nad+ dependent protein", "dependent protein deacetylases", "deacetylases sirt1", "sirt1 and sirt2", "sirt2 skokowa", "al. 2009 .", "2009 . g", ". g csf", "g csf induces", "csf induces the", "induces the nad+", "the nad+ generating", "nad+ generating enzyme", "enzyme nicotinamide", "phosphoribosyltransferase nampt", "nampt or", "that in turn", "in turn activates", "turn activates sirtuins", "sirtuins skokowa", "al. 2009 .
              gadd45a", "2009 .
              gadd45a and", ".
              gadd45a and gadd45b", "and gadd45b proteins", "gadd45b proteins are", "proteins are essential", "are essential for", "essential for stress", "for stress induced", "stress induced granulopoiesis", "induced granulopoiesis and", "granulopoiesis and granulocyte", "and granulocyte chemotaxis", "granulocyte chemotaxis by", "chemotaxis by activation", "by activation of", "activation of p38", "of p38 kinase", "kinase gupta", "gupta et al.", "2006 salerno", "salerno et al.", "al. 2012 .", "2012 . shp2", ". shp2 is", "shp2 is required", "is required for", "required for induction", "for induction of", "induction of cebpa", "of cebpa expression", "cebpa expression and", "expression and granulopoiesis", "and granulopoiesis in", "granulopoiesis in response", "in response to", "response to csf3", "csf or", "or other cytokines", "other cytokines independent", "cytokines independent of", "independent of shp2", "of shp2 mediated", "shp2 mediated erk", "mediated erk activation", "activation zhang", "et al. 2011", "al. 2011 .
              transcription", "2011 .
              transcription of", ".
              transcription of neutrophil", "of neutrophil granule", "neutrophil granule proteins", "proteins e.g.", "elane mpo", "mpo azu1", "azu1 defa4", "that play an", "play an essential", "an essential role", "essential role in", "role in bacterial", "in bacterial killing", "bacterial killing are", "killing are regulated", "regulated by cebpe", "by cebpe and", "cebpe and spi1", "pu.1 transcription", "factors gombart", "gombart et al.", "2003 nakajima", "nakajima et al.", "al. 2006 .", "2006 . runx1", ". runx1 and", "runx1 and lef1", "and lef1 also", "lef1 also regulate", "also regulate elane", "elane ela2", "ela2 mrna", "mrna expression by", "expression by binding", "by binding to", "binding to its", "to its promoter", "promoter li", "li et al.", "al. 2003 .", "neutrophilic granulocytes hereafter", "granulocytes hereafter called", "called granulocytes are", "granulocytes are distinguished", "are distinguished by multilobulated", "distinguished by multilobulated nuclei", "by multilobulated nuclei and", "multilobulated nuclei and presence", "nuclei and presence of", "and presence of cytoplasmic", "presence of cytoplasmic granules", "of cytoplasmic granules containing", "cytoplasmic granules containing antipathogenic", "granules containing antipathogenic proteins", "antipathogenic proteins reviewed", "proteins reviewed in", "reviewed in cowland and", "in cowland and borregaard", "cowland and borregaard 2016", "borregaard 2016 yin", "2016 yin and", "yin and heit 2018", "and heit 2018 .", "heit 2018 . granulocytes", "2018 . granulocytes comprise", ". granulocytes comprise eosinophils", "comprise eosinophils basophils", "basophils mast cells", "mast cells and", "cells and neutrophils", "and neutrophils all", "neutrophils all of", "all of which are", "of which are ultimately", "which are ultimately derived", "are ultimately derived from", "ultimately derived from hemopoietic", "derived from hemopoietic stem", "from hemopoietic stem cells", "stem cells hscs", "hscs a", "a self renewing population", "self renewing population of", "renewing population of stem", "population of stem cells", "of stem cells located", "stem cells located in", "cells located in the", "located in the bone", "in the bone marrow.", "the bone marrow. a", "bone marrow. a portion", "marrow. a portion of", "a portion of hscs", "portion of hscs exit", "of hscs exit self", "hscs exit self renewing", "exit self renewing proliferation", "self renewing proliferation and", "renewing proliferation and differentiate", "proliferation and differentiate to", "and differentiate to form", "differentiate to form multipotent", "to form multipotent progenitors", "multipotent progenitors mpps", "progenitors mpps .", "mpps . mpps then", ". mpps then differentiate", "mpps then differentiate to", "then differentiate to form", "differentiate to form common", "to form common myeloid", "form common myeloid progenitors", "myeloid progenitors cmps", "cmps as well", "as well as the", "well as the erythrocyte", "as the erythrocyte lineage.", "the erythrocyte lineage. cmps", "erythrocyte lineage. cmps further", "lineage. cmps further differentiate", "cmps further differentiate into", "further differentiate into granulocyte", "differentiate into granulocyte monocyte", "into granulocyte monocyte progenitors", "monocyte progenitors gmps", "gmps which can", "which can then differentiate", "can then differentiate into", "then differentiate into monocytes", "differentiate into monocytes or", "into monocytes or any", "monocytes or any of", "or any of the", "any of the types", "of the types of", "the types of granulocytes", "of granulocytes reviewed", "granulocytes reviewed in", "reviewed in fiedler and", "in fiedler and brunner", "fiedler and brunner 2012", "and brunner 2012 .", "brunner 2012 . granulocytes", "2012 . granulocytes are", ". granulocytes are the", "granulocytes are the most", "are the most abundant", "the most abundant leukocytes", "most abundant leukocytes in", "abundant leukocytes in peripheral", "leukocytes in peripheral blood.
              for", "in peripheral blood.
              for early", "peripheral blood.
              for early granulopoiesis", "blood.
              for early granulopoiesis the", "early granulopoiesis the cebpa", "the cebpa spi1", "pu.1 rar", "cbf and myb", "and myb transcription factors", "myb transcription factors are", "transcription factors are essential.", "factors are essential. cebpe", "essential. cebpe spi1", "cdp and hoxa10", "and hoxa10 transcription factors", "hoxa10 transcription factors initiate", "transcription factors initiate terminal", "factors initiate terminal neutrophil", "initiate terminal neutrophil differentiation.
              initially", "neutrophil differentiation.
              initially runx1", "differentiation.
              initially runx1 activates", "activates spi1 pu.1", "pu.1 which", "which is believed to", "is believed to be", "believed to be the", "to be the key", "be the key transcription", "the key transcription factor", "key transcription factor driving", "transcription factor driving the", "factor driving the formation", "driving the formation of", "the formation of mpps", "formation of mpps and", "of mpps and cmps", "and cmps reviewed", "cmps reviewed in", "reviewed in friedman 2007", "friedman 2007 fiedler", "2007 fiedler and", "brunner 2012 . spi1", ". spi1 in", "spi1 in turn", "turn activates expression", "activates expression of cebpa", "of cebpa an", "cebpa an indispensable", "an indispensable transcription factor", "indispensable transcription factor for", "transcription factor for granulopoiesis", "factor for granulopoiesis especially", "for granulopoiesis especially important", "granulopoiesis especially important in", "especially important in the", "important in the transition", "in the transition from", "the transition from cmp", "transition from cmp to", "from cmp to gmp", "to gmp inferred", "gmp inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in wilson", "homologs in wilson et", "in wilson et al.", "wilson et al. 2010", "al. 2010 guo", "2010 guo et", "guo et al. 2012", "al. 2012 guo", "2012 guo et", "guo et al. 2014", "al. 2014 cooper", "2014 cooper et", "cooper et al. 2015", "et al. 2015 .", "al. 2015 . cebpa", ". cebpa in", "cebpa in turn", "turn activates the", "activates the expression of", "the expression of several", "expression of several transcription", "of several transcription factors", "several transcription factors and", "transcription factors and receptors", "factors and receptors characteristic", "and receptors characteristic of", "receptors characteristic of granulocytes", "of granulocytes including", "granulocytes including cebpa", "including cebpa autoregulation", "autoregulation cebpe", "cebpe loke et", "loke et al. 2018", "al. 2018 and", "2018 and inferred", "and inferred from mouse", "mouse homologs in wang", "homologs in wang and", "in wang and friedman", "wang and friedman 2002", "friedman 2002 friedman", "2002 friedman et", "friedman et al. 2003", "2003 gfi1", "gfi1 inferred from", "mouse homologs in lidonnici", "homologs in lidonnici et", "in lidonnici et al.", "lidonnici et al. 2010", "2010 klf5", "klf5 federzoni et", "federzoni et al. 2014", "2014 il6r", "il6r inferred from", "mouse homologs in zhang", "homologs in zhang et", "in zhang et al.", "zhang et al. 1998", "1998 and", "and csf3r smith", "csf3r smith et", "smith et al. 1996", "et al. 1996 .", "al. 1996 . importantly", ". importantly cebpa", "importantly cebpa dimers", "cebpa dimers repress transcription", "dimers repress transcription of", "repress transcription of myc", "of myc c", "myc c myc", "myc johansen", "johansen et al. 2001", "al. 2001 and", "2001 and inferred", "mouse homologs in slomiany", "homologs in slomiany et", "in slomiany et al.", "slomiany et al. 2000", "al. 2000 porse", "2000 porse et", "porse et al. 2001", "et al. 2001 .", "al. 2001 . cebpa", "2001 . cebpa binds", ". cebpa binds cdk2", "cebpa binds cdk2 and", "binds cdk2 and cdk4", "and cdk4 wang", "cdk4 wang et", "wang et al. 2001", "al. 2001 which", "2001 which inhibits", "which inhibits their kinase", "inhibits their kinase activity", "their kinase activity by", "kinase activity by disrupting", "activity by disrupting their", "by disrupting their association", "disrupting their association with", "their association with cyclins", "association with cyclins thereby", "with cyclins thereby limiting", "cyclins thereby limiting proliferation", "thereby limiting proliferation and", "limiting proliferation and favoring", "proliferation and favoring differentiation", "and favoring differentiation of", "favoring differentiation of granulocyte", "differentiation of granulocyte progenitors", "of granulocyte progenitors during", "granulocyte progenitors during regular", "during regular \\steady", "regular \\steady state\\", "\\steady state\\ granulopoiesis", "granulopoiesis reviewed in", "reviewed in friedman 2015", "in friedman 2015 .", "friedman 2015 . the", "2015 . the transcription", ". the transcription factor", "the transcription factor gfi1", "transcription factor gfi1 regulates", "factor gfi1 regulates g", "gfi1 regulates g csf", "regulates g csf signaling", "g csf signaling and", "csf signaling and neutrophil", "signaling and neutrophil development", "and neutrophil development through", "neutrophil development through the", "development through the ras", "through the ras activator", "the ras activator rasgrp1", "activator rasgrp1 de", "rasgrp1 de la", "de la luz sierra", "la luz sierra et", "luz sierra et al.", "sierra et al. 2010", "et al. 2010 .
              inhibitors", "al. 2010 .
              inhibitors of", "2010 .
              inhibitors of dna", ".
              inhibitors of dna binding", "dna binding id", "id proteins id1", "proteins id1 and id2", "id1 and id2 regulate", "and id2 regulate granulopoiesis", "id2 regulate granulopoiesis and", "regulate granulopoiesis and eosinophil", "granulopoiesis and eosinophil production", "and eosinophil production such", "eosinophil production such that", "production such that id1", "such that id1 induces", "that id1 induces neutrophil", "id1 induces neutrophil development", "induces neutrophil development and", "neutrophil development and inhibits", "development and inhibits eosinophil", "and inhibits eosinophil differentiation", "eosinophil differentiation whereas", "differentiation whereas id2", "whereas id2 induces both", "id2 induces both eosinophil", "induces both eosinophil and", "both eosinophil and neutrophil", "eosinophil and neutrophil development", "neutrophil development buitenhuis", "development buitenhuis et", "buitenhuis et al. 2005", "al. 2005 skokowa", "2005 skokowa et", "skokowa et al. 2009", "et al. 2009 .
              major", "al. 2009 .
              major infection", "2009 .
              major infection activates", ".
              major infection activates emergency", "infection activates emergency granulopoiesis", "emergency granulopoiesis reviewed", "reviewed in manz and", "in manz and boettcher", "manz and boettcher 2014", "boettcher 2014 hirai", "2014 hirai et", "hirai et al. 2015", "2015 the", "the production of large", "production of large numbers", "of large numbers of", "large numbers of granulocytes", "numbers of granulocytes in", "of granulocytes in a", "granulocytes in a relatively", "in a relatively short", "a relatively short period", "relatively short period of", "short period of time.", "period of time. emergency", "of time. emergency granulopoiesis", "time. emergency granulopoiesis is", "emergency granulopoiesis is activated", "granulopoiesis is activated by", "is activated by cytokines", "by cytokines csf2", "csf2 gm csf", "gm csf and", "csf and especially", "especially csf3 g", "csf3 g csf", "g csf reviewed", "csf reviewed in", "reviewed in panopoulos and", "in panopoulos and watowich", "panopoulos and watowich 2008", "watowich 2008 liongue", "2008 liongue et", "liongue et al. 2009", "al. 2009 which", "2009 which bind", "bind receptors csf2r", "receptors csf2r and", "and csf3r respectively", "respectively resulting in", "resulting in expression of", "in expression of cebpb", "of cebpb which", "cebpb which interferes", "which interferes with repression", "interferes with repression of", "with repression of myc", "repression of myc by", "of myc by cebpa", "by cebpa inferred", "cebpa inferred from", "zhang et al. 2010", "al. 2010 and", "2010 and represses", "and represses myc less", "represses myc less than", "myc less than cebpa", "less than cebpa does", "cebpa does hirai", "does hirai et", "hirai et al. 2006", "2006 leading", "leading to proliferation of", "to proliferation of granulocyte", "proliferation of granulocyte progenitors", "of granulocyte progenitors prior", "granulocyte progenitors prior to", "progenitors prior to final", "prior to final differentiation.both", "final differentiation.both emergency", "differentiation.both emergency and", "emergency and steady state", "and steady state granulopoiesis", "steady state granulopoiesis are", "state granulopoiesis are regulated", "granulopoiesis are regulated by", "are regulated by direct", "regulated by direct interaction", "by direct interaction of", "direct interaction of cebpa", "of cebpa steady", "cebpa steady state", "steady state or", "state or cebpb", "or cebpb emergency", "emergency proteins with", "proteins with nad+ dependent", "with nad+ dependent protein", "nad+ dependent protein deacetylases", "protein deacetylases sirt1", "deacetylases sirt1 and", "and sirt2 skokowa", "sirt2 skokowa et", "et al. 2009 .", "al. 2009 . g", "2009 . g csf", ". g csf induces", "g csf induces the", "csf induces the nad+", "induces the nad+ generating", "the nad+ generating enzyme", "generating enzyme nicotinamide", "enzyme nicotinamide phosphoribosyltransferase", "nicotinamide phosphoribosyltransferase nampt", "nampt or pbef", "pbef that", "that in turn activates", "in turn activates sirtuins", "activates sirtuins skokowa", "sirtuins skokowa et", "et al. 2009 .
              gadd45a", "al. 2009 .
              gadd45a and", "2009 .
              gadd45a and gadd45b", ".
              gadd45a and gadd45b proteins", "and gadd45b proteins are", "gadd45b proteins are essential", "proteins are essential for", "are essential for stress", "essential for stress induced", "for stress induced granulopoiesis", "stress induced granulopoiesis and", "induced granulopoiesis and granulocyte", "granulopoiesis and granulocyte chemotaxis", "and granulocyte chemotaxis by", "granulocyte chemotaxis by activation", "chemotaxis by activation of", "by activation of p38", "activation of p38 kinase", "p38 kinase gupta", "kinase gupta et", "gupta et al. 2006", "al. 2006 salerno", "2006 salerno et", "salerno et al. 2012", "et al. 2012 .", "al. 2012 . shp2", "2012 . shp2 is", ". shp2 is required", "shp2 is required for", "is required for induction", "required for induction of", "for induction of cebpa", "induction of cebpa expression", "of cebpa expression and", "cebpa expression and granulopoiesis", "expression and granulopoiesis in", "and granulopoiesis in response", "granulopoiesis in response to", "in response to csf3", "to csf3 g", "g csf or", "csf or other", "or other cytokines independent", "other cytokines independent of", "cytokines independent of shp2", "independent of shp2 mediated", "of shp2 mediated erk", "shp2 mediated erk activation", "erk activation zhang", "activation zhang et", "zhang et al. 2011", "et al. 2011 .
              transcription", "al. 2011 .
              transcription of", "2011 .
              transcription of neutrophil", ".
              transcription of neutrophil granule", "of neutrophil granule proteins", "granule proteins e.g.", "proteins e.g. elane", "e.g. elane mpo", "defa4 that", "that play an essential", "play an essential role", "an essential role in", "essential role in bacterial", "role in bacterial killing", "in bacterial killing are", "bacterial killing are regulated", "killing are regulated by", "are regulated by cebpe", "regulated by cebpe and", "by cebpe and spi1", "and spi1 pu.1", "pu.1 transcription factors", "transcription factors gombart", "factors gombart et", "gombart et al. 2003", "al. 2003 nakajima", "2003 nakajima et", "nakajima et al. 2006", "et al. 2006 .", "al. 2006 . runx1", "2006 . runx1 and", ". runx1 and lef1", "runx1 and lef1 also", "and lef1 also regulate", "lef1 also regulate elane", "regulate elane ela2", "ela2 mrna expression", "mrna expression by binding", "expression by binding to", "by binding to its", "binding to its promoter", "its promoter li", "promoter li et", "li et al. 2003", "et al. 2003 .", "neutrophilic granulocytes hereafter called", "granulocytes hereafter called granulocytes", "hereafter called granulocytes are", "called granulocytes are distinguished", "granulocytes are distinguished by", "are distinguished by multilobulated nuclei", "distinguished by multilobulated nuclei and", "by multilobulated nuclei and presence", "multilobulated nuclei and presence of", "nuclei and presence of cytoplasmic", "and presence of cytoplasmic granules", "presence of cytoplasmic granules containing", "of cytoplasmic granules containing antipathogenic", "cytoplasmic granules containing antipathogenic proteins", "containing antipathogenic proteins reviewed", "antipathogenic proteins reviewed in", "proteins reviewed in cowland", "reviewed in cowland and borregaard", "in cowland and borregaard 2016", "and borregaard 2016 yin", "borregaard 2016 yin and", "2016 yin and heit", "yin and heit 2018 .", "and heit 2018 . granulocytes", "heit 2018 . granulocytes comprise", "2018 . granulocytes comprise eosinophils", "granulocytes comprise eosinophils basophils", "eosinophils basophils mast", "mast cells and neutrophils", "and neutrophils all of", "neutrophils all of which", "all of which are ultimately", "of which are ultimately derived", "which are ultimately derived from", "are ultimately derived from hemopoietic", "ultimately derived from hemopoietic stem", "derived from hemopoietic stem cells", "hemopoietic stem cells hscs", "hscs a self", "a self renewing population of", "self renewing population of stem", "renewing population of stem cells", "population of stem cells located", "of stem cells located in", "stem cells located in the", "cells located in the bone", "located in the bone marrow.", "in the bone marrow. a", "the bone marrow. a portion", "bone marrow. a portion of", "marrow. a portion of hscs", "a portion of hscs exit", "portion of hscs exit self", "of hscs exit self renewing", "hscs exit self renewing proliferation", "exit self renewing proliferation and", "self renewing proliferation and differentiate", "renewing proliferation and differentiate to", "proliferation and differentiate to form", "and differentiate to form multipotent", "differentiate to form multipotent progenitors", "form multipotent progenitors mpps", "multipotent progenitors mpps .", "progenitors mpps . mpps", "mpps . mpps then differentiate", ". mpps then differentiate to", "mpps then differentiate to form", "then differentiate to form common", "differentiate to form common myeloid", "to form common myeloid progenitors", "common myeloid progenitors cmps", "progenitors cmps as", "cmps as well as", "as well as the erythrocyte", "well as the erythrocyte lineage.", "as the erythrocyte lineage. cmps", "the erythrocyte lineage. cmps further", "erythrocyte lineage. cmps further differentiate", "lineage. cmps further differentiate into", "cmps further differentiate into granulocyte", "further differentiate into granulocyte monocyte", "differentiate into granulocyte monocyte progenitors", "granulocyte monocyte progenitors gmps", "progenitors gmps which", "gmps which can then", "which can then differentiate into", "can then differentiate into monocytes", "then differentiate into monocytes or", "differentiate into monocytes or any", "into monocytes or any of", "monocytes or any of the", "or any of the types", "any of the types of", "of the types of granulocytes", "types of granulocytes reviewed", "of granulocytes reviewed in", "granulocytes reviewed in fiedler", "reviewed in fiedler and brunner", "in fiedler and brunner 2012", "fiedler and brunner 2012 .", "and brunner 2012 . granulocytes", "brunner 2012 . granulocytes are", "2012 . granulocytes are the", ". granulocytes are the most", "granulocytes are the most abundant", "are the most abundant leukocytes", "the most abundant leukocytes in", "most abundant leukocytes in peripheral", "abundant leukocytes in peripheral blood.
              for", "leukocytes in peripheral blood.
              for early", "in peripheral blood.
              for early granulopoiesis", "peripheral blood.
              for early granulopoiesis the", "blood.
              for early granulopoiesis the cebpa", "granulopoiesis the cebpa spi1", "cebpa spi1 pu.1", "rar cbf and", "cbf and myb transcription", "and myb transcription factors are", "myb transcription factors are essential.", "transcription factors are essential. cebpe", "are essential. cebpe spi1", "cebpe spi1 sp1", "spi1 sp1 cdp", "sp1 cdp and", "cdp and hoxa10 transcription", "and hoxa10 transcription factors initiate", "hoxa10 transcription factors initiate terminal", "transcription factors initiate terminal neutrophil", "factors initiate terminal neutrophil differentiation.
              initially", "terminal neutrophil differentiation.
              initially runx1", "neutrophil differentiation.
              initially runx1 activates", "differentiation.
              initially runx1 activates spi1", "runx1 activates spi1 pu.1", "pu.1 which is", "which is believed to be", "is believed to be the", "believed to be the key", "to be the key transcription", "be the key transcription factor", "the key transcription factor driving", "key transcription factor driving the", "transcription factor driving the formation", "factor driving the formation of", "driving the formation of mpps", "the formation of mpps and", "formation of mpps and cmps", "mpps and cmps reviewed", "and cmps reviewed in", "cmps reviewed in friedman", "in friedman 2007 fiedler", "friedman 2007 fiedler and", "2007 fiedler and brunner", "and brunner 2012 . spi1", "2012 . spi1 in", ". spi1 in turn", "in turn activates expression", "turn activates expression of", "expression of cebpa an", "of cebpa an indispensable", "cebpa an indispensable transcription", "an indispensable transcription factor for", "indispensable transcription factor for granulopoiesis", "transcription factor for granulopoiesis especially", "factor for granulopoiesis especially important", "for granulopoiesis especially important in", "granulopoiesis especially important in the", "especially important in the transition", "important in the transition from", "in the transition from cmp", "the transition from cmp to", "transition from cmp to gmp", "cmp to gmp inferred", "to gmp inferred from", "gmp inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in wilson", "mouse homologs in wilson et", "homologs in wilson et al.", "in wilson et al. 2010", "et al. 2010 guo", "al. 2010 guo et", "2010 guo et al.", "et al. 2012 guo", "al. 2012 guo et", "2012 guo et al.", "et al. 2014 cooper", "al. 2014 cooper et", "2014 cooper et al.", "cooper et al. 2015 .", "et al. 2015 . cebpa", "2015 . cebpa in", ". cebpa in turn", "in turn activates the", "turn activates the expression", "activates the expression of several", "the expression of several transcription", "expression of several transcription factors", "of several transcription factors and", "several transcription factors and receptors", "transcription factors and receptors characteristic", "factors and receptors characteristic of", "and receptors characteristic of granulocytes", "characteristic of granulocytes including", "of granulocytes including cebpa", "cebpe loke et al.", "et al. 2018 and", "al. 2018 and inferred", "2018 and inferred from", "and inferred from mouse homologs", "from mouse homologs in wang", "mouse homologs in wang and", "homologs in wang and friedman", "in wang and friedman 2002", "and friedman 2002 friedman", "friedman 2002 friedman et", "2002 friedman et al.", "al. 2003 gfi1", "gfi1 inferred from mouse", "from mouse homologs in lidonnici", "mouse homologs in lidonnici et", "homologs in lidonnici et al.", "in lidonnici et al. 2010", "al. 2010 klf5", "klf5 federzoni et al.", "al. 2014 il6r", "il6r inferred from mouse", "from mouse homologs in zhang", "mouse homologs in zhang et", "homologs in zhang et al.", "in zhang et al. 1998", "al. 1998 and", "1998 and csf3r", "and csf3r smith et", "csf3r smith et al.", "smith et al. 1996 .", "et al. 1996 . importantly", "1996 . importantly cebpa", ". importantly cebpa dimers", "importantly cebpa dimers repress", "cebpa dimers repress transcription of", "dimers repress transcription of myc", "transcription of myc c", "of myc c myc", "c myc johansen", "myc johansen et", "et al. 2001 and", "al. 2001 and inferred", "2001 and inferred from", "from mouse homologs in slomiany", "mouse homologs in slomiany et", "homologs in slomiany et al.", "in slomiany et al. 2000", "et al. 2000 porse", "al. 2000 porse et", "2000 porse et al.", "porse et al. 2001 .", "et al. 2001 . cebpa", "al. 2001 . cebpa binds", "2001 . cebpa binds cdk2", ". cebpa binds cdk2 and", "cebpa binds cdk2 and cdk4", "cdk2 and cdk4 wang", "and cdk4 wang et", "cdk4 wang et al.", "et al. 2001 which", "al. 2001 which inhibits", "2001 which inhibits their", "which inhibits their kinase activity", "inhibits their kinase activity by", "their kinase activity by disrupting", "kinase activity by disrupting their", "activity by disrupting their association", "by disrupting their association with", "disrupting their association with cyclins", "their association with cyclins thereby", "association with cyclins thereby limiting", "with cyclins thereby limiting proliferation", "cyclins thereby limiting proliferation and", "thereby limiting proliferation and favoring", "limiting proliferation and favoring differentiation", "proliferation and favoring differentiation of", "and favoring differentiation of granulocyte", "favoring differentiation of granulocyte progenitors", "differentiation of granulocyte progenitors during", "of granulocyte progenitors during regular", "progenitors during regular \\steady", "during regular \\steady state\\", "state\\ granulopoiesis reviewed", "granulopoiesis reviewed in friedman", "reviewed in friedman 2015 .", "in friedman 2015 . the", "friedman 2015 . the transcription", "2015 . the transcription factor", ". the transcription factor gfi1", "the transcription factor gfi1 regulates", "transcription factor gfi1 regulates g", "factor gfi1 regulates g csf", "gfi1 regulates g csf signaling", "regulates g csf signaling and", "g csf signaling and neutrophil", "csf signaling and neutrophil development", "signaling and neutrophil development through", "and neutrophil development through the", "neutrophil development through the ras", "development through the ras activator", "through the ras activator rasgrp1", "ras activator rasgrp1 de", "activator rasgrp1 de la", "rasgrp1 de la luz", "de la luz sierra et", "la luz sierra et al.", "luz sierra et al. 2010", "sierra et al. 2010 .
              inhibitors", "et al. 2010 .
              inhibitors of", "al. 2010 .
              inhibitors of dna", "2010 .
              inhibitors of dna binding", "of dna binding id", "binding id proteins", "id proteins id1 and", "proteins id1 and id2 regulate", "id1 and id2 regulate granulopoiesis", "and id2 regulate granulopoiesis and", "id2 regulate granulopoiesis and eosinophil", "regulate granulopoiesis and eosinophil production", "granulopoiesis and eosinophil production such", "and eosinophil production such that", "eosinophil production such that id1", "production such that id1 induces", "such that id1 induces neutrophil", "that id1 induces neutrophil development", "id1 induces neutrophil development and", "induces neutrophil development and inhibits", "neutrophil development and inhibits eosinophil", "development and inhibits eosinophil differentiation", "inhibits eosinophil differentiation whereas", "eosinophil differentiation whereas id2", "differentiation whereas id2 induces", "whereas id2 induces both eosinophil", "id2 induces both eosinophil and", "induces both eosinophil and neutrophil", "both eosinophil and neutrophil development", "and neutrophil development buitenhuis", "neutrophil development buitenhuis et", "development buitenhuis et al.", "et al. 2005 skokowa", "al. 2005 skokowa et", "2005 skokowa et al.", "skokowa et al. 2009 .
              major", "et al. 2009 .
              major infection", "al. 2009 .
              major infection activates", "2009 .
              major infection activates emergency", ".
              major infection activates emergency granulopoiesis", "activates emergency granulopoiesis reviewed", "emergency granulopoiesis reviewed in", "granulopoiesis reviewed in manz", "reviewed in manz and boettcher", "in manz and boettcher 2014", "and boettcher 2014 hirai", "boettcher 2014 hirai et", "2014 hirai et al.", "al. 2015 the", "2015 the production", "the production of large numbers", "production of large numbers of", "of large numbers of granulocytes", "large numbers of granulocytes in", "numbers of granulocytes in a", "of granulocytes in a relatively", "granulocytes in a relatively short", "in a relatively short period", "a relatively short period of", "relatively short period of time.", "short period of time. emergency", "period of time. emergency granulopoiesis", "of time. emergency granulopoiesis is", "time. emergency granulopoiesis is activated", "emergency granulopoiesis is activated by", "granulopoiesis is activated by cytokines", "activated by cytokines csf2", "cytokines csf2 gm", "gm csf and especially", "csf and especially csf3", "and especially csf3 g", "especially csf3 g csf", "g csf reviewed in", "csf reviewed in panopoulos", "reviewed in panopoulos and watowich", "in panopoulos and watowich 2008", "and watowich 2008 liongue", "watowich 2008 liongue et", "2008 liongue et al.", "et al. 2009 which", "al. 2009 which bind", "2009 which bind receptors", "which bind receptors csf2r", "bind receptors csf2r and", "receptors csf2r and csf3r", "csf2r and csf3r respectively", "csf3r respectively resulting", "respectively resulting in expression", "resulting in expression of cebpb", "expression of cebpb which", "of cebpb which interferes", "cebpb which interferes with", "which interferes with repression of", "interferes with repression of myc", "with repression of myc by", "repression of myc by cebpa", "myc by cebpa inferred", "by cebpa inferred from", "cebpa inferred from mouse", "in zhang et al. 2010", "et al. 2010 and", "al. 2010 and represses", "2010 and represses myc", "and represses myc less than", "represses myc less than cebpa", "myc less than cebpa does", "than cebpa does hirai", "cebpa does hirai et", "does hirai et al.", "al. 2006 leading", "2006 leading to", "leading to proliferation of granulocyte", "to proliferation of granulocyte progenitors", "proliferation of granulocyte progenitors prior", "of granulocyte progenitors prior to", "granulocyte progenitors prior to final", "progenitors prior to final differentiation.both", "to final differentiation.both emergency", "final differentiation.both emergency and", "differentiation.both emergency and steady", "emergency and steady state granulopoiesis", "and steady state granulopoiesis are", "steady state granulopoiesis are regulated", "state granulopoiesis are regulated by", "granulopoiesis are regulated by direct", "are regulated by direct interaction", "regulated by direct interaction of", "by direct interaction of cebpa", "interaction of cebpa steady", "of cebpa steady state", "steady state or cebpb", "cebpb emergency proteins", "emergency proteins with nad+", "proteins with nad+ dependent protein", "with nad+ dependent protein deacetylases", "dependent protein deacetylases sirt1", "protein deacetylases sirt1 and", "deacetylases sirt1 and sirt2", "sirt1 and sirt2 skokowa", "and sirt2 skokowa et", "sirt2 skokowa et al.", "skokowa et al. 2009 .", "et al. 2009 . g", "al. 2009 . g csf", "2009 . g csf induces", ". g csf induces the", "g csf induces the nad+", "csf induces the nad+ generating", "induces the nad+ generating enzyme", "nad+ generating enzyme nicotinamide", "generating enzyme nicotinamide phosphoribosyltransferase", "phosphoribosyltransferase nampt or", "or pbef that", "pbef that in", "that in turn activates sirtuins", "turn activates sirtuins skokowa", "activates sirtuins skokowa et", "sirtuins skokowa et al.", "skokowa et al. 2009 .
              gadd45a", "et al. 2009 .
              gadd45a and", "al. 2009 .
              gadd45a and gadd45b", "2009 .
              gadd45a and gadd45b proteins", ".
              gadd45a and gadd45b proteins are", "and gadd45b proteins are essential", "gadd45b proteins are essential for", "proteins are essential for stress", "are essential for stress induced", "essential for stress induced granulopoiesis", "for stress induced granulopoiesis and", "stress induced granulopoiesis and granulocyte", "induced granulopoiesis and granulocyte chemotaxis", "granulopoiesis and granulocyte chemotaxis by", "and granulocyte chemotaxis by activation", "granulocyte chemotaxis by activation of", "chemotaxis by activation of p38", "by activation of p38 kinase", "of p38 kinase gupta", "p38 kinase gupta et", "kinase gupta et al.", "et al. 2006 salerno", "al. 2006 salerno et", "2006 salerno et al.", "salerno et al. 2012 .", "et al. 2012 . shp2", "al. 2012 . shp2 is", "2012 . shp2 is required", ". shp2 is required for", "shp2 is required for induction", "is required for induction of", "required for induction of cebpa", "for induction of cebpa expression", "induction of cebpa expression and", "of cebpa expression and granulopoiesis", "cebpa expression and granulopoiesis in", "expression and granulopoiesis in response", "and granulopoiesis in response to", "granulopoiesis in response to csf3", "response to csf3 g", "to csf3 g csf", "g csf or other", "csf or other cytokines", "or other cytokines independent of", "other cytokines independent of shp2", "cytokines independent of shp2 mediated", "independent of shp2 mediated erk", "of shp2 mediated erk activation", "mediated erk activation zhang", "erk activation zhang et", "activation zhang et al.", "zhang et al. 2011 .
              transcription", "et al. 2011 .
              transcription of", "al. 2011 .
              transcription of neutrophil", "2011 .
              transcription of neutrophil granule", ".
              transcription of neutrophil granule proteins", "neutrophil granule proteins e.g.", "granule proteins e.g. elane", "elane mpo azu1", "mpo azu1 defa4", "defa4 that play", "that play an essential role", "play an essential role in", "an essential role in bacterial", "essential role in bacterial killing", "role in bacterial killing are", "in bacterial killing are regulated", "bacterial killing are regulated by", "killing are regulated by cebpe", "are regulated by cebpe and", "regulated by cebpe and spi1", "cebpe and spi1 pu.1", "spi1 pu.1 transcription", "transcription factors gombart et", "factors gombart et al.", "et al. 2003 nakajima", "al. 2003 nakajima et", "2003 nakajima et al.", "nakajima et al. 2006 .", "et al. 2006 . runx1", "al. 2006 . runx1 and", "2006 . runx1 and lef1", ". runx1 and lef1 also", "runx1 and lef1 also regulate", "and lef1 also regulate elane", "also regulate elane ela2", "elane ela2 mrna", "ela2 mrna expression by", "mrna expression by binding to", "expression by binding to its", "by binding to its promoter", "to its promoter li", "its promoter li et", "promoter li et al.", "li et al. 2003 ." ] }, { "record_id": "GLY_000594_1_1215", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9617629", "r hsa", "hsa 9617629", "r hsa 9617629" ] }, { "record_id": "GLY_000594_1_1215", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of foxo", "foxo transcriptional", "transcriptional activity", "activity by", "by acetylation", "regulation of foxo", "of foxo transcriptional", "foxo transcriptional activity", "transcriptional activity by", "activity by acetylation", "regulation of foxo transcriptional", "of foxo transcriptional activity", "foxo transcriptional activity by", "transcriptional activity by acetylation", "regulation of foxo transcriptional activity", "of foxo transcriptional activity by", "foxo transcriptional activity by acetylation", "oxidative stress", "stress induces", "induces acetylation", "acetylation of", "foxo transcription", "transcription factors", "which changes", "changes the", "the preference", "preference of", "factors for", "for target", "target dna", "dna sequences.", "sequences. histone", "histone deacetylases", "deacetylases sirt1", "sirt1 and", "and sirt3", "sirt3 deacetylate", "deacetylate foxo", "brunet et", "et al.", "al. 2004", "daitoku et", "motta et", "dansen et", "al. 2009", "kim et", "al. 2010", "tseng et", "al. 2013", "reviewed by", "by hisahara", "hisahara et", "al. 2005", "2005 .
              acetylation", ".
              acetylation can", "can also", "also regulate", "regulate foxo", "foxo localization", "overriding phosphorylation", "frescas et", "bertaggia et", "al. 2012", "2012 .", "oxidative stress induces", "stress induces acetylation", "induces acetylation of", "acetylation of foxo", "of foxo transcription", "foxo transcription factors", "factors which", "which changes the", "changes the preference", "the preference of", "preference of foxo", "transcription factors for", "factors for target", "for target dna", "target dna sequences.", "dna sequences. histone", "sequences. histone deacetylases", "histone deacetylases sirt1", "deacetylases sirt1 and", "sirt1 and sirt3", "and sirt3 deacetylate", "sirt3 deacetylate foxo", "deacetylate foxo transcription", "factors brunet", "brunet et al.", "et al. 2004", "2004 daitoku", "daitoku et al.", "2004 motta", "motta et al.", "2004 dansen", "dansen et al.", "et al. 2009", "2009 kim", "kim et al.", "et al. 2010", "2010 tseng", "tseng et al.", "et al. 2013", "2013 reviewed", "reviewed by hisahara", "by hisahara et", "hisahara et al.", "et al. 2005", "al. 2005 .
              acetylation", "2005 .
              acetylation can", ".
              acetylation can also", "can also regulate", "also regulate foxo", "regulate foxo localization", "localization overriding", "phosphorylation frescas", "frescas et al.", "2005 bertaggia", "bertaggia et al.", "et al. 2012", "al. 2012 .", "oxidative stress induces acetylation", "stress induces acetylation of", "induces acetylation of foxo", "acetylation of foxo transcription", "of foxo transcription factors", "transcription factors which", "factors which changes", "which changes the preference", "changes the preference of", "the preference of foxo", "preference of foxo transcription", "foxo transcription factors for", "transcription factors for target", "factors for target dna", "for target dna sequences.", "target dna sequences. histone", "dna sequences. histone deacetylases", "sequences. histone deacetylases sirt1", "histone deacetylases sirt1 and", "deacetylases sirt1 and sirt3", "sirt1 and sirt3 deacetylate", "and sirt3 deacetylate foxo", "sirt3 deacetylate foxo transcription", "deacetylate foxo transcription factors", "transcription factors brunet", "factors brunet et", "brunet et al. 2004", "al. 2004 daitoku", "2004 daitoku et", "daitoku et al. 2004", "al. 2004 motta", "2004 motta et", "motta et al. 2004", "al. 2004 dansen", "2004 dansen et", "dansen et al. 2009", "al. 2009 kim", "2009 kim et", "kim et al. 2010", "al. 2010 tseng", "2010 tseng et", "tseng et al. 2013", "al. 2013 reviewed", "2013 reviewed by", "reviewed by hisahara et", "by hisahara et al.", "hisahara et al. 2005", "et al. 2005 .
              acetylation", "al. 2005 .
              acetylation can", "2005 .
              acetylation can also", ".
              acetylation can also regulate", "can also regulate foxo", "also regulate foxo localization", "foxo localization overriding", "localization overriding phosphorylation", "overriding phosphorylation frescas", "phosphorylation frescas et", "frescas et al. 2005", "al. 2005 bertaggia", "2005 bertaggia et", "bertaggia et al. 2012", "et al. 2012 .", "oxidative stress induces acetylation of", "stress induces acetylation of foxo", "induces acetylation of foxo transcription", "acetylation of foxo transcription factors", "foxo transcription factors which", "transcription factors which changes", "factors which changes the", "which changes the preference of", "changes the preference of foxo", "the preference of foxo transcription", "preference of foxo transcription factors", "of foxo transcription factors for", "foxo transcription factors for target", "transcription factors for target dna", "factors for target dna sequences.", "for target dna sequences. histone", "target dna sequences. histone deacetylases", "dna sequences. histone deacetylases sirt1", "sequences. histone deacetylases sirt1 and", "histone deacetylases sirt1 and sirt3", "deacetylases sirt1 and sirt3 deacetylate", "sirt1 and sirt3 deacetylate foxo", "and sirt3 deacetylate foxo transcription", "sirt3 deacetylate foxo transcription factors", "foxo transcription factors brunet", "transcription factors brunet et", "factors brunet et al.", "et al. 2004 daitoku", "al. 2004 daitoku et", "2004 daitoku et al.", "et al. 2004 motta", "al. 2004 motta et", "2004 motta et al.", "et al. 2004 dansen", "al. 2004 dansen et", "2004 dansen et al.", "et al. 2009 kim", "al. 2009 kim et", "2009 kim et al.", "et al. 2010 tseng", "al. 2010 tseng et", "2010 tseng et al.", "et al. 2013 reviewed", "al. 2013 reviewed by", "2013 reviewed by hisahara", "reviewed by hisahara et al.", "by hisahara et al. 2005", "hisahara et al. 2005 .
              acetylation", "et al. 2005 .
              acetylation can", "al. 2005 .
              acetylation can also", "2005 .
              acetylation can also regulate", ".
              acetylation can also regulate foxo", "can also regulate foxo localization", "regulate foxo localization overriding", "foxo localization overriding phosphorylation", "overriding phosphorylation frescas et", "phosphorylation frescas et al.", "et al. 2005 bertaggia", "al. 2005 bertaggia et", "2005 bertaggia et al.", "bertaggia et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1216", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9623433", "r hsa", "hsa 9623433", "r hsa 9623433" ] }, { "record_id": "GLY_000594_1_1216", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nr1h2 &", "& nr1h3", "nr1h3 regulate", "regulate gene", "gene expression", "expression to", "to control", "control bile", "bile acid", "acid homeostasis", "nr1h2 & nr1h3", "& nr1h3 regulate", "nr1h3 regulate gene", "regulate gene expression", "gene expression to", "expression to control", "to control bile", "control bile acid", "bile acid homeostasis", "nr1h2 & nr1h3 regulate", "& nr1h3 regulate gene", "nr1h3 regulate gene expression", "regulate gene expression to", "gene expression to control", "expression to control bile", "to control bile acid", "control bile acid homeostasis", "nr1h2 & nr1h3 regulate gene", "& nr1h3 regulate gene expression", "nr1h3 regulate gene expression to", "regulate gene expression to control", "gene expression to control bile", "expression to control bile acid", "to control bile acid homeostasis", "liver x", "x receptors", "receptors nr1h3", "lxr alpha", "and nr1h2", "lxr beta", "are sterol", "sterol responsive", "responsive transcription", "transcription factors", "factors that", "that become", "become activated", "activated upon", "upon the", "the engagement", "engagement with", "with their", "their cognate", "cognate oxysterol", "oxysterol ligands.", "ligands. besides", "besides inducing", "inducing a", "a genetic", "genetic program", "program aimed", "aimed to", "to 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"become activated upon", "activated upon the", "upon the engagement", "the engagement with", "engagement with their", "with their cognate", "their cognate oxysterol", "cognate oxysterol ligands.", "oxysterol ligands. besides", "ligands. besides inducing", "besides inducing a", "inducing a genetic", "a genetic program", "genetic program aimed", "program aimed to", "aimed to reduce", "to reduce the", "reduce the cellular", "the cellular sterol", "cellular sterol load", "load ligand", "ligand activated nr1h2", "activated nr1h2 &", "& nr1h3 also", "nr1h3 also modulate", "also modulate the", "modulate the expression", "the expression and", "expression and activity", "and activity of", "activity of genes", "of genes controlling", "genes controlling bile", "controlling bile acid", "bile acid synthesis", "synthesis transport", "transport and metabolism", "and metabolism such", "metabolism such as", "such as bile", "as bile acid", "bile acid glucuronidating", "acid glucuronidating enzyme", 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"with their cognate oxysterol", "their cognate oxysterol ligands.", "cognate oxysterol ligands. besides", "oxysterol ligands. besides inducing", "ligands. besides inducing a", "besides inducing a genetic", "inducing a genetic program", "a genetic program aimed", "genetic program aimed to", "program aimed to reduce", "aimed to reduce the", "to reduce the cellular", "reduce the cellular sterol", "the cellular sterol load", "sterol load ligand", "load ligand activated", "ligand activated nr1h2 &", "activated nr1h2 & nr1h3", "nr1h2 & nr1h3 also", "& nr1h3 also modulate", "nr1h3 also modulate the", "also modulate the expression", "modulate the expression and", "the expression and activity", "expression and activity of", "and activity of genes", "activity of genes controlling", "of genes controlling bile", "genes controlling bile acid", "controlling bile acid synthesis", "acid synthesis transport", "synthesis transport and", "transport and metabolism such", "and metabolism such as", "metabolism such as bile", "such as bile acid", "as bile acid glucuronidating", "bile acid glucuronidating enzyme", "acid glucuronidating enzyme ugt1a3", "glucuronidating enzyme ugt1a3 which", "enzyme ugt1a3 which converts", "ugt1a3 which converts hydrophobic", "which converts hydrophobic bile", "converts hydrophobic bile acids", "hydrophobic bile acids into", "bile acids into polar", "acids into polar metabolites", "into polar metabolites that", "polar metabolites that can", "metabolites that can be", "that can be excreted", "can be excreted in", "be excreted in the", "excreted in the urine", "the urine verreault", "urine verreault m", "verreault m et al.", "m et al. 2006", "et al. 2006 .", "x receptors nr1h3 lxr", "receptors nr1h3 lxr alpha", "lxr alpha and nr1h2", "and nr1h2 lxr beta", "lxr beta are sterol", "beta are sterol responsive", "are sterol responsive transcription factors", "sterol responsive transcription factors that", "responsive transcription factors that become", 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metabolites", "acids into polar metabolites that", "into polar metabolites that can", "polar metabolites that can be", "metabolites that can be excreted", "that can be excreted in", "can be excreted in the", "be excreted in the urine", "in the urine verreault", "the urine verreault m", "urine verreault m et", "verreault m et al. 2006", "m et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1217", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9634600", "r hsa", "hsa 9634600", "r hsa 9634600" ] }, { "record_id": "GLY_000594_1_1217", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of glycolysis", "glycolysis by", "by fructose", "fructose 2", "2 6", "6 bisphosphate", "bisphosphate metabolism", "regulation of glycolysis", "of glycolysis by", "glycolysis by fructose", "by fructose 2", "fructose 2 6", "2 6 bisphosphate", "6 bisphosphate metabolism", "regulation of glycolysis by", "of 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stimulation is mcf7 breast", "stimulation is mcf7 breast cancer", "is mcf7 breast cancer cells", "mcf7 breast cancer cells and", "breast cancer cells and contributes", "cancer cells and contributes estrogen", "cells and contributes estrogen dependent", "and contributes estrogen dependent proliferation", "contributes estrogen dependent proliferation through", "estrogen dependent proliferation through mapk", "dependent proliferation through mapk pathway", "proliferation through mapk pathway activation", "mapk pathway activation castoria", "pathway activation castoria et", "activation castoria et al", "castoria et al 2004", "et al 2004 ." ] }, { "record_id": "GLY_000594_1_1219", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9645460", "r hsa", "hsa 9645460", "r hsa 9645460" ] }, { "record_id": "GLY_000594_1_1219", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "alpha protein", "protein kinase", "kinase 1", "1 signaling", "signaling pathway", "alpha protein kinase", "protein kinase 1", "kinase 1 signaling", "1 signaling pathway", "alpha protein kinase 1", "protein kinase 1 signaling", "kinase 1 signaling pathway", "alpha protein kinase 1 signaling", "protein kinase 1 signaling pathway", "immune recognition", "recognition of", "of pathogen", "pathogen associated", "associated molecular", "molecular patterns", "by pattern", "pattern recognition", "recognition receptors", "often activates", "activates proinflammatory", "proinflammatory nuclear", "nuclear factor", "factor kappa", "kappa b", "nf \u03bab", "signalling. lipopolysaccharide", "is a", "a well", "well known", "known pamp", "pamp produced", "produced by", "by gram", "gram negative", "negative bacteria.", "bacteria. lps", "lps is", "is recognized", "recognized by", "by toll", "toll like", "like receptor", "receptor 4", "and is", "a strong", "strong activator", "activator of", "of nf", "\u03bab inflammatory", "inflammatory responses", "akashi s", "s et", "et al.", "al. 2003", "2003 .", ". lps", "is also", "also recognized", "recognized in", "in the", "the cytosol", "cytosol by", "by mouse", "mouse caspase", "caspase 11", "11 and", "and related", "related human", "human caspase", "caspase 4", "4 and", "and caspase", "caspase 5", "which stimulate", "stimulate pyroptosis", "a proinflammatory", "proinflammatory form", "form of", "of cell", "cell death", "kayagaki n", "n et", "al. 2011", "shi j", "j et", "al. 2015", "2015 .", ". key", "key metabolic", "metabolic intermediates", "intermediates in", "in lps", "lps biosynthesis", "d glycero", "glycero \u03b2", "\u03b2 d", "d manno", "manno heptose", "heptose 1", "1 7", "7 bisphosphate", "and adp", "adp l", "l glycero", "adp heptose", "were reported", "reported to", "to activate", "activate the", "the nf", "\u03bab pathway", "pathway and", "and trigger", "trigger the", "the innate", "innate immune", "immune responses", "milivojevic m", "m et", "al. 2017", "zimmermann s", "zhou p", "p et", "al. 2018", "garc\u00eda weber", "weber d", "2018 .", ". adp", "heptose but", "but not", "not hbp", "hbp can", "can enter", "enter host", "host cells", "cells autonomously", ". during", "during infection", "heptose or", "or hbp", "hbp translocate", "translocate into", "into the", "the host", "host cytosol", "cytosol where", "where their", "their presence", "presence is", "is sensed", "sensed by", "by alpha", "heptose directly", "directly binds", "binds and", "and activates", "activates alpk1", "garcia weber", "d et", "hbp is", "is converted", "converted by", "by host", "host derived", "derived adenylyltransferases", "such as", "as nicotinamide", "nicotinamide nucleotide", "nucleotide adenylyltransferases", "to adp", "heptose 7", "7 p", "a substrate", "substrate which", "which can", "can then", "then activate", "activate alpk1", ". the", "the adp", "heptose binding", "binding to", "to alpk1", "alpk1 is", "is thought", "thought to", "to trigger", "trigger conformational", "conformational changes", "changes and", "and stimulate", "stimulate the", "the kinase", "kinase domain", "domain of", "of alpk1", ". alpk1", "alpk1 kinase", "kinase activity", "activity in", "in turn", "turn leads", "leads to", "to the", "the phosphorylation", "phosphorylation dependent", "dependent oligomerization", "oligomerization of", "of the", "the tumor", "tumor necrosis", "necrosis factor", "tnf \u03b1", "receptor\u2013associated factor", "traf \u2013interacting", "\u2013interacting protein", "protein with", "with the", "the forkhead", "forkhead associated", "associated domain", ". this", "this process", "process activates", "activates traf6", "traf6 oligomerization", "oligomerization and", "and ubiquitination", "and the", "the recruitment", "recruitment of", "of transforming", "transforming growth", "growth factor", "factor \u03b2", "\u03b2 activated", "activated kinase", "binding protein", "protein 2", "a component", "component of", "the tak1", "ea ck", "ck et", "al. 2004", "gaudet rg", "rg et", "2017 .", "this tifa", "tifa oligomer", "oligomer signaling", "signaling platform", "platform was", "was given", "given the", "the term:", "term: tifasome.", "tifasome. tifasome", "tifasome activated", "activated tak1", "tak1 induces", "induces nf", "\u03bab nuclear", "nuclear translocation", "translocation and", "and proinflammatory", "proinflammatory gene", "gene expression.", "expression. the", "the alpk1", "alpk1 tifa", "tifa signaling", "pathway has", "has been", "been identified", "identified in", "in human", "human embryonic", "embryonic kidney", "kidney cells", "intestinal epithelial", "epithelial cells", "gastric cells", "cells and", "and cervical", "cervical cancer", "cancer cells", "stein sc", "sc et", "gall a", "a et", ". in", "in vivo", "vivo studies", "studies demonstrate", "demonstrate that", "that adp", "heptose and", "and burkholderia", "burkholderia cenocepacia", "cenocepacia trigger", "trigger massive", "massive inflammatory", "responses with", "with increased", "increased production", "production of", "of several", "several nf", "\u03bab dependent", "dependent cytokines", "cytokines and", "and chemokines", "chemokines in", "in wild", "wild type", "not in", "in alpk1", "alpk1 /", "2018 .

              this", ".

              this reactome", "reactome module", "module describes", "describes alpk1", "alpk1 as", "as a", "a cytosolic", "cytosolic innate", "immune receptor", "receptor for", "for bacterial", "bacterial adp", "adp heptose.", "immune recognition of", "recognition of pathogen", "of pathogen associated", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "pamps by", "by pattern recognition", "pattern recognition receptors", "receptors prr", "prr often", "often activates proinflammatory", "activates proinflammatory nuclear", "proinflammatory nuclear factor", "nuclear factor kappa", "factor kappa b", "b nf", "\u03bab signalling.", "lipopolysaccharide lps", "is a well", "a well known", "well known pamp", "known pamp produced", "pamp produced by", "produced by gram", "by gram negative", "gram negative bacteria.", "negative bacteria. lps", "bacteria. lps is", "lps is recognized", "is recognized by", "recognized by toll", "by toll like", "toll like receptor", "like receptor 4", "4 tlr4", "tlr4 and", "and is a", "is a strong", "a strong activator", "strong activator of", "activator of nf", "of nf \u03bab", "nf \u03bab inflammatory", "\u03bab inflammatory responses", "responses akashi", "akashi s et", "s et al.", "et al. 2003", "al. 2003 .", "2003 . lps", ". lps is", "lps is also", "is also recognized", "also recognized in", "recognized in the", "in the cytosol", "the cytosol by", "cytosol by mouse", "by mouse caspase", "mouse caspase 11", "caspase 11 and", "11 and related", "and related human", "related human caspase", "human caspase 4", "caspase 4 and", "4 and caspase", "and caspase 5", "5 which", "which stimulate pyroptosis", "pyroptosis a", "a proinflammatory form", "proinflammatory form of", "form of cell", "of cell death", "death kayagaki", "kayagaki n et", "n et al.", "et al. 2011", "2011 shi", "shi j et", "j et al.", "et al. 2015", "al. 2015 .", "2015 . key", ". key metabolic", "key metabolic intermediates", "metabolic intermediates in", "intermediates in lps", "in lps biosynthesis", "biosynthesis d", "d glycero \u03b2", "glycero \u03b2 d", "\u03b2 d manno", "d manno heptose", "manno heptose 1", "heptose 1 7", "1 7 bisphosphate", "bisphosphate hbp", "hbp and", "and adp l", "adp l glycero", "l glycero \u03b2", "heptose adp", "heptose were", "were reported to", "reported to activate", "to activate the", "activate the nf", "the nf \u03bab", "nf \u03bab pathway", "\u03bab pathway and", "pathway and trigger", "and trigger the", "trigger the innate", "the innate immune", "innate immune responses", "responses milivojevic", "milivojevic m et", "m et al.", "et al. 2017", "2017 zimmermann", "zimmermann s et", "2017 zhou", "zhou p et", "p et al.", "et al. 2018", "2018 garc\u00eda", "garc\u00eda weber d", "d 2018", "2018 . adp", ". adp heptose", "adp heptose but", "heptose but not", "but not hbp", "not hbp can", "hbp can enter", "can enter host", "enter host cells", "host cells autonomously", "autonomously zhou", "al. 2018 .", "2018 . during", ". during infection", "infection adp", "adp heptose or", "heptose or hbp", "or hbp translocate", "hbp translocate into", "translocate into the", "into the host", "the host cytosol", "host cytosol where", "cytosol where their", "where their presence", "their presence is", "presence is sensed", "is sensed by", "sensed by alpha", "by alpha protein", "1 alpk1", "adp heptose directly", "heptose directly binds", "directly binds and", "binds and activates", "and activates alpk1", "alpk1 garcia", "garcia weber d", "weber d et", "d et al.", "2018 zhou", "instead hbp", "hbp is converted", "is converted by", "converted by host", "by host derived", "host derived adenylyltransferases", "adenylyltransferases such", "such as nicotinamide", "as nicotinamide nucleotide", "nicotinamide nucleotide adenylyltransferases", "adenylyltransferases to", "to adp heptose", "adp heptose 7", "heptose 7 p", "p a", "a substrate which", "substrate which can", "which can then", "can then activate", "then activate alpk1", "alpk1 zhou", "2018 . the", ". the adp", "the adp heptose", "adp heptose binding", "heptose binding to", "binding to alpk1", "to alpk1 is", "alpk1 is thought", "is thought to", "thought to trigger", "to trigger conformational", "trigger conformational changes", "conformational changes and", "changes and stimulate", "and stimulate the", "stimulate the kinase", "the kinase domain", "kinase domain of", "domain of alpk1", "2018 . alpk1", ". alpk1 kinase", "alpk1 kinase activity", "kinase activity in", "activity in turn", "in turn leads", "turn leads to", "leads to the", "to the phosphorylation", "the phosphorylation dependent", "phosphorylation dependent oligomerization", "dependent oligomerization of", "oligomerization of the", "of the tumor", "the tumor necrosis", "tumor necrosis factor", "factor tnf", "\u03b1 receptor\u2013associated", "factor traf", "traf \u2013interacting protein", "\u2013interacting protein with", "protein with the", "with the forkhead", "the forkhead associated", "forkhead associated domain", "domain tifa", "2018 . this", ". this process", "this process activates", "process activates traf6", "activates traf6 oligomerization", "traf6 oligomerization and", "oligomerization and ubiquitination", "ubiquitination and", "and the recruitment", "the recruitment of", "recruitment of transforming", "of transforming growth", "transforming growth factor", "growth factor \u03b2", "factor \u03b2 activated", "\u03b2 activated kinase", "activated kinase 1", "1 tak1", "tak1 binding", "binding protein 2", "2 tab2", "a component of", "component of the", "of the tak1", "tak1 map3k7", "map3k7 complex", "complex ea", "ea ck et", "ck et al.", "et al. 2004", "2004 gaudet", "gaudet rg et", "rg et al.", "al. 2017 .", "2017 . this", ". this tifa", "this tifa oligomer", "tifa oligomer signaling", "oligomer signaling platform", "signaling platform was", "platform was given", "was given the", "given the term:", "the term: tifasome.", "term: tifasome. tifasome", "tifasome. tifasome activated", "tifasome activated tak1", "activated tak1 induces", "tak1 induces nf", "induces nf \u03bab", "nf \u03bab nuclear", "\u03bab nuclear translocation", "nuclear translocation and", "translocation and proinflammatory", "and proinflammatory gene", "proinflammatory gene expression.", "gene expression. the", "expression. the alpk1", "the alpk1 tifa", "alpk1 tifa signaling", "tifa signaling pathway", "signaling pathway has", "pathway has been", "has been identified", "been identified in", "identified in human", "in human embryonic", "human embryonic kidney", "embryonic kidney cells", "cells intestinal", "intestinal epithelial cells", "cells gastric", "gastric cells and", "cells and cervical", "and cervical cancer", "cervical cancer cells", "cells gaudet", "2015 2017", "2017 stein", "stein sc et", "sc et al.", "2017 gall", "gall a et", "a et al.", "2017 milivojevic", "2018 . in", ". in vivo", "in vivo studies", "vivo studies demonstrate", "studies demonstrate that", "demonstrate that adp", "that adp heptose", "adp heptose and", "heptose and burkholderia", "and burkholderia cenocepacia", "burkholderia cenocepacia trigger", "cenocepacia trigger massive", "trigger massive inflammatory", "massive inflammatory responses", "inflammatory responses with", "responses with increased", "with increased production", "increased production of", "production of several", "of several nf", "several nf \u03bab", "nf \u03bab dependent", "\u03bab dependent cytokines", "dependent cytokines and", "cytokines and chemokines", "and chemokines in", "chemokines in wild", "in wild type", "type wt", "but not in", "not in alpk1", "in alpk1 /", "/ mice", "mice zhou", "al. 2018 .

              this", "2018 .

              this reactome", ".

              this reactome module", "reactome module describes", "module describes alpk1", "describes alpk1 as", "alpk1 as a", "as a cytosolic", "a cytosolic innate", "cytosolic innate immune", "innate immune receptor", "immune receptor for", "receptor for bacterial", "for bacterial adp", "bacterial adp heptose.", "immune recognition of pathogen", "recognition of pathogen associated", "of pathogen associated molecular", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps by pattern", "by pattern recognition receptors", "recognition receptors prr", "prr often activates", "often activates proinflammatory nuclear", "activates proinflammatory nuclear factor", "proinflammatory nuclear factor kappa", "nuclear factor kappa b", "kappa b nf", "b nf \u03bab", "nf \u03bab signalling.", "\u03bab signalling. lipopolysaccharide", "signalling. lipopolysaccharide lps", "lps is a", "is a well known", "a well known pamp", "well known pamp produced", "known pamp produced by", "pamp produced by gram", "produced by gram negative", "by gram negative bacteria.", "gram negative bacteria. lps", "negative bacteria. lps is", "bacteria. lps is recognized", "lps is recognized by", "is recognized by toll", "recognized by toll like", "by toll like receptor", "toll like receptor 4", "receptor 4 tlr4", "tlr4 and is", "and is a strong", "is a strong activator", "a strong activator of", "strong activator of nf", "activator of nf \u03bab", "of nf \u03bab inflammatory", "nf \u03bab inflammatory responses", "inflammatory responses akashi", "responses akashi s", "akashi s et al.", "s et al. 2003", "et al. 2003 .", "al. 2003 . lps", "2003 . lps is", ". lps is also", "lps is also recognized", "is also recognized in", "also recognized in the", "recognized in the cytosol", "in the cytosol by", "the cytosol by mouse", "cytosol by mouse caspase", "by mouse caspase 11", "mouse caspase 11 and", "caspase 11 and related", "11 and related human", "and related human caspase", "related human caspase 4", "human caspase 4 and", "caspase 4 and caspase", "4 and caspase 5", "caspase 5 which", "5 which stimulate", "stimulate pyroptosis a", "pyroptosis a proinflammatory", "a proinflammatory form of", "proinflammatory form of cell", "form of cell death", "cell death kayagaki", "death kayagaki n", "kayagaki n et al.", "n et al. 2011", "al. 2011 shi", "2011 shi j", "shi j et al.", "j et al. 2015", "et al. 2015 .", "al. 2015 . key", "2015 . key metabolic", ". key metabolic intermediates", "key metabolic intermediates in", "metabolic intermediates in lps", "intermediates in lps biosynthesis", "lps biosynthesis d", "biosynthesis d glycero", "d glycero \u03b2 d", "glycero \u03b2 d manno", "\u03b2 d manno heptose", "d manno heptose 1", "manno heptose 1 7", "heptose 1 7 bisphosphate", "7 bisphosphate hbp", "hbp and adp", "and adp l glycero", "adp l glycero \u03b2", "l glycero \u03b2 d", "manno heptose adp", "heptose adp heptose", "adp heptose were", "heptose were reported", "were reported to activate", "reported to activate the", "to activate the nf", "activate the nf \u03bab", "the nf \u03bab pathway", "nf \u03bab pathway and", "\u03bab pathway and trigger", "pathway and trigger the", "and trigger the innate", "trigger the innate immune", "the innate immune responses", "immune responses milivojevic", "responses milivojevic m", "milivojevic m et al.", "m et al. 2017", "al. 2017 zimmermann", "2017 zimmermann s", "zimmermann s et al.", "s et al. 2017", "al. 2017 zhou", "2017 zhou p", "zhou p et al.", "p et al. 2018", "al. 2018 garc\u00eda", "2018 garc\u00eda weber", "weber d 2018", "d 2018 .", "2018 . adp heptose", ". adp heptose but", "adp heptose but not", "heptose but not hbp", "but not hbp can", "not hbp can enter", "hbp can enter host", "can enter host cells", "enter host cells autonomously", "cells autonomously zhou", "autonomously zhou p", "et al. 2018 .", "al. 2018 . during", "2018 . during infection", "during infection adp", "infection adp heptose", "adp heptose or hbp", "heptose or hbp translocate", "or hbp translocate into", "hbp translocate into the", "translocate into the host", "into the host cytosol", "the host cytosol where", "host cytosol where their", "cytosol where their presence", "where their presence is", "their presence is sensed", "presence is sensed by", "is sensed by alpha", "sensed by alpha protein", "by alpha protein kinase", "kinase 1 alpk1", "alpk1 zimmermann", "al. 2018 . adp", ". adp heptose directly", "adp heptose directly binds", "heptose directly binds and", "directly binds and activates", "binds and activates alpk1", "activates alpk1 garcia", "alpk1 garcia weber", "garcia weber d et", "weber d et al.", "d et al. 2018", "al. 2018 zhou", "2018 zhou p", "2018 instead", "instead hbp is", "hbp is converted by", "is converted by host", "converted by host derived", "by host derived adenylyltransferases", "derived adenylyltransferases such", "adenylyltransferases such as", "such as nicotinamide nucleotide", "as nicotinamide nucleotide adenylyltransferases", "nucleotide adenylyltransferases to", "adenylyltransferases to adp", "to adp heptose 7", "adp heptose 7 p", "7 p a", "p a substrate", "a substrate which can", "substrate which can then", "which can then activate", "can then activate alpk1", "activate alpk1 zhou", "alpk1 zhou p", "al. 2018 . the", "2018 . the adp", ". the adp heptose", "the adp heptose binding", "adp heptose binding to", "heptose binding to alpk1", "binding to alpk1 is", "to alpk1 is thought", "alpk1 is thought to", "is thought to trigger", "thought to trigger conformational", "to trigger conformational changes", "trigger conformational changes and", "conformational changes and stimulate", "changes and stimulate the", "and stimulate the kinase", "stimulate the kinase domain", "the kinase domain of", "kinase domain of alpk1", "of alpk1 zhou", "al. 2018 . alpk1", "2018 . alpk1 kinase", ". alpk1 kinase activity", "alpk1 kinase activity in", "kinase activity in turn", "activity in turn leads", "in turn leads to", "turn leads to the", "leads to the phosphorylation", "to the phosphorylation dependent", "the phosphorylation dependent oligomerization", "phosphorylation dependent oligomerization of", "dependent oligomerization of the", "oligomerization of the tumor", "of the tumor necrosis", "the tumor necrosis factor", "necrosis factor tnf", "factor tnf \u03b1", "tnf \u03b1 receptor\u2013associated", "\u03b1 receptor\u2013associated factor", "receptor\u2013associated factor traf", "factor traf \u2013interacting", "traf \u2013interacting protein with", "\u2013interacting protein with the", "protein with the forkhead", "with the forkhead associated", "the forkhead associated domain", "associated domain tifa", "tifa zimmermann", "al. 2018 . this", "2018 . this process", ". this process activates", "this process activates traf6", "process activates traf6 oligomerization", "activates traf6 oligomerization and", "traf6 oligomerization and ubiquitination", "and ubiquitination and", "ubiquitination and the", "and the recruitment of", "the recruitment of transforming", "recruitment of transforming growth", "of transforming growth factor", "transforming growth factor \u03b2", "growth factor \u03b2 activated", "factor \u03b2 activated kinase", "\u03b2 activated kinase 1", "kinase 1 tak1", "tak1 binding protein", "protein 2 tab2", "tab2 a", "a component of the", "component of the tak1", "the tak1 map3k7", "complex ea ck", "ea ck et al.", "ck et al. 2004", "al. 2004 gaudet", "2004 gaudet rg", "gaudet rg et al.", "rg et al. 2017", "et al. 2017 .", "al. 2017 . this", "2017 . this tifa", ". this tifa oligomer", "this tifa oligomer signaling", "tifa oligomer signaling platform", "oligomer signaling platform was", "signaling platform was given", "platform was given the", "was given the term:", "given the term: tifasome.", "the term: tifasome. tifasome", "term: tifasome. tifasome activated", "tifasome. tifasome activated tak1", "tifasome activated tak1 induces", "activated tak1 induces nf", "tak1 induces nf \u03bab", "induces nf \u03bab nuclear", "nf \u03bab nuclear translocation", "\u03bab nuclear translocation and", "nuclear translocation and proinflammatory", "translocation and proinflammatory gene", "and proinflammatory gene expression.", "proinflammatory gene expression. the", "gene expression. the alpk1", "expression. the alpk1 tifa", "the alpk1 tifa signaling", "alpk1 tifa signaling pathway", "tifa signaling pathway has", "signaling pathway has been", "pathway has been identified", "has been identified in", "been identified in human", "identified in human embryonic", "in human embryonic kidney", "human embryonic kidney cells", "kidney cells intestinal", "cells intestinal epithelial", "epithelial cells gastric", "cells gastric cells", "gastric cells and cervical", "cells and cervical cancer", "and cervical cancer cells", "cancer cells gaudet", "cells gaudet rg", "rg et al. 2015", "al. 2015 2017", "2017 stein sc", "stein sc et al.", "sc et al. 2017", "al. 2017 gall", "2017 gall a", "gall a et al.", "a et al. 2017", "al. 2017 milivojevic", "2017 milivojevic m", "al. 2018 . in", "2018 . in vivo", ". in vivo studies", "in vivo studies demonstrate", "vivo studies demonstrate that", "studies demonstrate that adp", "demonstrate that adp heptose", "that adp heptose and", "adp heptose and burkholderia", "heptose and burkholderia cenocepacia", "and burkholderia cenocepacia trigger", "burkholderia cenocepacia trigger massive", "cenocepacia trigger massive inflammatory", "trigger massive inflammatory responses", "massive inflammatory responses with", "inflammatory responses with increased", "responses with increased production", "with increased production of", "increased production of several", "production of several nf", "of several nf \u03bab", "several nf \u03bab dependent", "nf \u03bab dependent cytokines", "\u03bab dependent cytokines and", "dependent cytokines and chemokines", "cytokines and chemokines in", "and chemokines in wild", "chemokines in wild type", "wild type wt", "wt but", "but not in alpk1", "not in alpk1 /", "alpk1 / mice", "mice zhou p", "et al. 2018 .

              this", "al. 2018 .

              this reactome", "2018 .

              this reactome module", ".

              this reactome module describes", "reactome module describes alpk1", "module describes alpk1 as", "describes alpk1 as a", "alpk1 as a cytosolic", "as a cytosolic innate", "a cytosolic innate immune", "cytosolic innate immune receptor", "innate immune receptor for", "immune receptor for bacterial", "receptor for bacterial adp", "for bacterial adp heptose.", "immune recognition of pathogen associated", "recognition of pathogen associated molecular", "of pathogen associated molecular patterns", "associated molecular patterns pamps", "patterns pamps by", "pamps by pattern recognition", "pattern recognition receptors prr", "receptors prr often", "prr often activates proinflammatory", "often activates proinflammatory nuclear factor", "activates proinflammatory nuclear factor kappa", "proinflammatory nuclear factor kappa b", "factor kappa b nf", "kappa b nf \u03bab", "nf \u03bab signalling. lipopolysaccharide", "lipopolysaccharide lps is", "lps is a well", "is a well known pamp", "a well known pamp produced", "well known pamp produced by", "known pamp produced by gram", "pamp produced by gram negative", "produced by gram negative bacteria.", "by gram negative bacteria. lps", "gram negative bacteria. lps is", "negative bacteria. lps is recognized", "bacteria. lps is recognized by", "lps is recognized by toll", "is recognized by toll like", "recognized by toll like receptor", "by toll like receptor 4", "like receptor 4 tlr4", "4 tlr4 and", "tlr4 and is a", "and is a strong activator", "is a strong activator of", "a strong activator of nf", "strong activator of nf \u03bab", "activator of nf \u03bab inflammatory", "of nf \u03bab inflammatory responses", "\u03bab inflammatory responses akashi", "inflammatory responses akashi s", "responses akashi s et", "akashi s et al. 2003", "s et al. 2003 .", "et al. 2003 . lps", "al. 2003 . lps is", "2003 . lps is also", ". lps is also recognized", "lps is also recognized in", "is also recognized in the", "also recognized in the cytosol", "recognized in the cytosol by", "in the cytosol by mouse", "the cytosol by mouse caspase", "cytosol by mouse caspase 11", "by mouse caspase 11 and", "mouse caspase 11 and related", "caspase 11 and related human", "11 and related human caspase", "and related human caspase 4", "related human caspase 4 and", "human caspase 4 and caspase", "caspase 4 and caspase 5", "and caspase 5 which", "caspase 5 which stimulate", "5 which stimulate pyroptosis", "which stimulate pyroptosis a", "stimulate pyroptosis a proinflammatory", "pyroptosis a proinflammatory form", "a proinflammatory form of cell", "proinflammatory form of cell death", "of cell death kayagaki", "cell death kayagaki n", "death kayagaki n et", "kayagaki n et al. 2011", "et al. 2011 shi", "al. 2011 shi j", "2011 shi j et", "shi j et al. 2015", "j et al. 2015 .", "et al. 2015 . key", "al. 2015 . key metabolic", "2015 . key metabolic intermediates", ". key metabolic intermediates in", "key metabolic intermediates in lps", "metabolic intermediates in lps biosynthesis", "in lps biosynthesis d", "lps biosynthesis d glycero", "biosynthesis d glycero \u03b2", "d glycero \u03b2 d manno", "glycero \u03b2 d manno heptose", "\u03b2 d manno heptose 1", "d manno heptose 1 7", "manno heptose 1 7 bisphosphate", "1 7 bisphosphate hbp", "bisphosphate hbp and", "hbp and adp l", "and adp l glycero \u03b2", "adp l glycero \u03b2 d", "l glycero \u03b2 d manno", "d manno heptose adp", "manno heptose adp heptose", "adp heptose were reported", "heptose were reported to", "were reported to activate the", "reported to activate the nf", "to activate the nf \u03bab", "activate the nf \u03bab pathway", "the nf \u03bab pathway and", "nf \u03bab pathway and trigger", "\u03bab pathway and trigger the", "pathway and trigger the innate", "and trigger the innate immune", "trigger the innate immune responses", "innate immune responses milivojevic", "immune responses milivojevic m", "responses milivojevic m et", "milivojevic m et al. 2017", "et al. 2017 zimmermann", "al. 2017 zimmermann s", "2017 zimmermann s et", "zimmermann s et al. 2017", "et al. 2017 zhou", "al. 2017 zhou p", "2017 zhou p et", "zhou p et al. 2018", "et al. 2018 garc\u00eda", "al. 2018 garc\u00eda weber", "2018 garc\u00eda weber d", "garc\u00eda weber d 2018", "weber d 2018 .", "d 2018 . adp", "2018 . adp heptose but", ". adp heptose but not", "adp heptose but not hbp", "heptose but not hbp can", "but not hbp can enter", "not hbp can enter host", "hbp can enter host cells", "can enter host cells autonomously", "host cells autonomously zhou", "cells autonomously zhou p", "autonomously zhou p et", "p et al. 2018 .", "et al. 2018 . during", "al. 2018 . during infection", ". during infection adp", "during infection adp heptose", "infection adp heptose or", "adp heptose or hbp translocate", "heptose or hbp translocate into", "or hbp translocate into the", "hbp translocate into the host", "translocate into the host cytosol", "into the host cytosol where", "the host cytosol where their", "host cytosol where their presence", "cytosol where their presence is", "where their presence is sensed", "their presence is sensed by", "presence is sensed by alpha", "is sensed by alpha protein", "sensed by alpha protein kinase", "by alpha protein kinase 1", "protein kinase 1 alpk1", "alpk1 zimmermann s", "et al. 2018 . adp", "al. 2018 . adp heptose", "2018 . adp heptose directly", ". adp heptose directly binds", "adp heptose directly binds and", "heptose directly binds and activates", "directly binds and activates alpk1", "and activates alpk1 garcia", "activates alpk1 garcia weber", "alpk1 garcia weber d", "garcia weber d et al.", "weber d et al. 2018", "et al. 2018 zhou", "al. 2018 zhou p", "2018 zhou p et", "al. 2018 instead", "instead hbp is converted", "hbp is converted by host", "is converted by host derived", "converted by host derived adenylyltransferases", "host derived adenylyltransferases such", "derived adenylyltransferases such as", "adenylyltransferases such as nicotinamide", "such as nicotinamide nucleotide adenylyltransferases", "nicotinamide nucleotide adenylyltransferases to", "nucleotide adenylyltransferases to adp", "adenylyltransferases to adp heptose", "to adp heptose 7 p", "heptose 7 p a", "7 p a substrate", "p a substrate which", "a substrate which can then", "substrate which can then activate", "which can then activate alpk1", "then activate alpk1 zhou", "activate alpk1 zhou p", "alpk1 zhou p et", "et al. 2018 . the", "al. 2018 . the adp", "2018 . the adp heptose", ". the adp heptose binding", "the adp heptose binding to", "adp heptose binding to alpk1", "heptose binding to alpk1 is", "binding to alpk1 is thought", "to alpk1 is thought to", "alpk1 is thought to trigger", "is thought to trigger conformational", "thought to trigger conformational changes", "to trigger conformational changes and", "trigger conformational changes and stimulate", "conformational changes and stimulate the", "changes and stimulate the kinase", "and stimulate the kinase domain", "stimulate the kinase domain of", "the kinase domain of alpk1", "domain of alpk1 zhou", "of alpk1 zhou p", "et al. 2018 . alpk1", "al. 2018 . alpk1 kinase", "2018 . alpk1 kinase activity", ". alpk1 kinase activity in", "alpk1 kinase activity in turn", "kinase activity in turn leads", "activity in turn leads to", "in turn leads to the", "turn leads to the phosphorylation", "leads to the phosphorylation dependent", "to the phosphorylation dependent oligomerization", "the phosphorylation dependent oligomerization of", "phosphorylation dependent oligomerization of the", "dependent oligomerization of the tumor", "oligomerization of the tumor necrosis", "of the tumor necrosis factor", "tumor necrosis factor tnf", "necrosis factor tnf \u03b1", "tnf \u03b1 receptor\u2013associated factor", "receptor\u2013associated factor traf \u2013interacting", "factor traf \u2013interacting protein", "traf \u2013interacting protein with the", "\u2013interacting protein with the forkhead", "protein with the forkhead associated", "with the forkhead associated domain", "forkhead associated domain tifa", "tifa zimmermann s", "et al. 2018 . this", "al. 2018 . this process", "2018 . this process activates", ". this process activates traf6", "this process activates traf6 oligomerization", "process activates traf6 oligomerization and", "activates traf6 oligomerization and ubiquitination", "oligomerization and ubiquitination and", "and ubiquitination and the", "ubiquitination and the recruitment", "and the recruitment of transforming", "the recruitment of transforming growth", "recruitment of transforming growth factor", "of transforming growth factor \u03b2", "transforming growth factor \u03b2 activated", "growth factor \u03b2 activated kinase", "factor \u03b2 activated kinase 1", "activated kinase 1 tak1", "1 tak1 binding", "tak1 binding protein 2", "binding protein 2 tab2", "tab2 a component", "a component of the tak1", "of the tak1 map3k7", "tak1 map3k7 complex", "map3k7 complex ea", "complex ea ck et", "ea ck et al. 2004", "et al. 2004 gaudet", "al. 2004 gaudet rg", "2004 gaudet rg et", "gaudet rg et al. 2017", "rg et al. 2017 .", "et al. 2017 . this", "al. 2017 . this tifa", "2017 . this tifa oligomer", ". this tifa oligomer signaling", "this tifa oligomer signaling platform", "tifa oligomer signaling platform was", "oligomer signaling platform was given", "signaling platform was given the", "platform was given the term:", "was given the term: tifasome.", "given the term: tifasome. tifasome", "the term: tifasome. tifasome activated", "term: tifasome. tifasome activated tak1", "tifasome. tifasome activated tak1 induces", "tifasome activated tak1 induces nf", "activated tak1 induces nf \u03bab", "tak1 induces nf \u03bab nuclear", "induces nf \u03bab nuclear translocation", "nf \u03bab nuclear translocation and", "\u03bab nuclear translocation and proinflammatory", "nuclear translocation and proinflammatory gene", "translocation and proinflammatory gene expression.", "and proinflammatory gene expression. the", "proinflammatory gene expression. the alpk1", "gene expression. the alpk1 tifa", "expression. the alpk1 tifa signaling", "the alpk1 tifa signaling pathway", "alpk1 tifa signaling pathway has", "tifa signaling pathway has been", "signaling pathway has been identified", "pathway has been identified in", "has been identified in human", "been identified in human embryonic", "identified in human embryonic kidney", "in human embryonic kidney cells", "embryonic kidney cells intestinal", "kidney cells intestinal epithelial", "cells intestinal epithelial cells", "intestinal epithelial cells gastric", "epithelial cells gastric cells", "cells gastric cells and", "gastric cells and cervical cancer", "cells and cervical cancer cells", "cervical cancer cells gaudet", "cancer cells gaudet rg", "cells gaudet rg et", "gaudet rg et al. 2015", "et al. 2015 2017", "2015 2017 stein", "2017 stein sc et", "stein sc et al. 2017", "et al. 2017 gall", "al. 2017 gall a", "2017 gall a et", "gall a et al. 2017", "et al. 2017 milivojevic", "al. 2017 milivojevic m", "2017 milivojevic m et", "et al. 2018 . in", "al. 2018 . in vivo", "2018 . in vivo studies", ". in vivo studies demonstrate", "in vivo studies demonstrate that", "vivo studies demonstrate that adp", "studies demonstrate that adp heptose", "demonstrate that adp heptose and", "that adp heptose and burkholderia", "adp heptose and burkholderia cenocepacia", "heptose and burkholderia cenocepacia trigger", "and burkholderia cenocepacia trigger massive", "burkholderia cenocepacia trigger massive inflammatory", "cenocepacia trigger massive inflammatory responses", "trigger massive inflammatory responses with", "massive inflammatory responses with increased", "inflammatory responses with increased production", "responses with increased production of", "with increased production of several", "increased production of several nf", "production of several nf \u03bab", "of several nf \u03bab dependent", "several nf \u03bab dependent cytokines", "nf \u03bab dependent cytokines and", "\u03bab dependent cytokines and chemokines", "dependent cytokines and chemokines in", "cytokines and chemokines in wild", "and chemokines in wild type", "in wild type wt", "wt but not", "but not in alpk1 /", "in alpk1 / mice", "/ mice zhou", "mice zhou p et", "p et al. 2018 .

              this", "et al. 2018 .

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"cytoplasmic adaptor myd88 and iraks", "myd88 and iraks downstream", "and iraks downstream of", "iraks downstream of which", "downstream of which the signaling", "of which the signaling pathways", "which the signaling pathways are", "the signaling pathways are divided", "signaling pathways are divided to", "pathways are divided to induce", "are divided to induce either", "divided to induce either inflammatory", "to induce either inflammatory cytokines", "induce either inflammatory cytokines or", "either inflammatory cytokines or type", "inflammatory cytokines or type i", "cytokines or type i ifns." ] }, { "record_id": "GLY_000594_1_1224", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975577", "r hsa", "hsa 975577", "r hsa 975577" ] }, { "record_id": "GLY_000594_1_1224", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "n glycan", "glycan antennae", "antennae elongation", "n glycan antennae", 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              for", "glycosylation.
              for a", "a better", "better annotation", "annotation of", "the reactions", "reactions and", "and genes", "genes involved", "in the", "the synthesis", "synthesis of", "of complex", "and hybrid", "glycans we", "we recommend", "recommend the", "the glycogene", "glycogene database", "ito h.", "h. et", "et al", "for annotations", "annotations of", "of genes", "and the", "the consortium", "consortium for", "for functional", "functional genomics", "for annotation", "of glycan", "glycan structures", "structures and", "and reactions.", "reactions. moreover", "a computationally", "computationally inferred", "inferred prediction", "prediction for", "for the", "the structure", "of this", "this network", "network is", "is available", "available through", "through the", "the software", "software glycovis", "hossler p.", "p. et.", "et. al.", "al. 2006", "2006 .", "n glycans are", "glycans are further", "are further modified", "further modified after", "modified after the", "after the commitment", "the commitment to", "commitment to complex", "to complex or", "complex or hybrid", "or hybrid n", "hybrid n glycans.", "n glycans. the", "glycans. the exact", "the exact structure", "exact structure of", "structure of the", "of the network", "the network of", "network of metabolic", "of metabolic reactions", "metabolic reactions involved", "reactions involved is", "involved is complex", "is complex and", "complex and not", "and not yet", "not yet validated", "yet validated experimentally.", "validated experimentally. here", "experimentally. here we", "here we will", "we will show", "will show a", "show a generic", "a generic reaction", "generic reaction for", "reaction for each", "for each of", "each of the", "of the genes", "the genes known", "genes known to", "known to be", "to be involved", "be involved in", "involved in n", "in n glycosylation.
              for", "n glycosylation.
              for a", "glycosylation.
              for a better", "a better annotation", "better annotation of", "annotation of the", "of the reactions", "the reactions and", "reactions and genes", "and genes involved", "genes involved in", "involved in the", "in the synthesis", "the synthesis of", "synthesis of complex", "of complex and", "complex and hybrid", "and hybrid n", "hybrid n glycans", "n glycans we", "glycans we recommend", "we recommend the", "recommend the glycogene", "the glycogene database", "database ito", "ito h. et", "h. et al", "al 2010", "http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for", "for annotations of", "annotations of genes", "genes and", "and the consortium", "the consortium for", "consortium for functional", "for functional genomics", "genomics http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp", "for annotation of", "annotation of glycan", "of glycan structures", "glycan structures and", "structures and reactions.", "and reactions. moreover", "moreover a", "a computationally inferred", "computationally inferred prediction", "inferred prediction for", "prediction for the", "for the structure", "the structure of", "structure of this", "of this network", "this network is", "network is available", "is available through", "available through the", "through the software", "the software glycovis", "glycovis hossler", "hossler p. et.", "p. et. al.", "et. al. 2006", "al. 2006 .", "n glycans are further", "glycans are further modified", "are further modified after", "further modified after the", "modified after the commitment", "after the commitment to", "the commitment to complex", "commitment to complex or", "to complex or hybrid", "complex or hybrid n", "or hybrid n glycans.", "hybrid n glycans. the", "n glycans. the exact", "glycans. the exact structure", "the exact structure of", "exact structure of the", "structure of the network", "of the network of", "the network of metabolic", "network of metabolic reactions", "of metabolic reactions involved", "metabolic reactions involved is", "reactions involved is complex", "involved is complex and", "is complex and not", "complex and not yet", "and not yet validated", "not yet validated experimentally.", "yet validated experimentally. here", "validated experimentally. here we", "experimentally. here we will", "here we will show", "we will show a", "will show a generic", "show a generic reaction", "a generic reaction for", "generic reaction for each", "reaction for each of", "for each of the", "each of the genes", "of the genes known", "the genes known to", "genes known to be", "known to be involved", "to be involved in", "be involved in n", "involved in n glycosylation.
              for", "in n glycosylation.
              for a", "n glycosylation.
              for a better", "glycosylation.
              for a better annotation", "a better annotation of", "better annotation of the", "annotation of the reactions", "of the reactions and", "the reactions and genes", "reactions and genes involved", "and genes involved in", "genes involved in the", "involved in the synthesis", "in the synthesis of", "the synthesis of complex", "synthesis of complex and", "of complex and hybrid", "complex and hybrid n", "and hybrid n glycans", "hybrid n glycans we", "n glycans we recommend", "glycans we recommend the", "we recommend the glycogene", "recommend the glycogene database", "glycogene database ito", "database ito h.", "ito h. et al", "et al 2010", "2010 http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp", "http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for annotations", "for annotations of genes", "of genes and", "genes and the", "and the consortium for", "the consortium for functional", "consortium for functional genomics", "functional genomics http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp", "http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for annotation", "for annotation of glycan", "annotation of glycan structures", "of glycan structures and", "glycan structures and reactions.", "structures and reactions. moreover", "reactions. moreover a", "moreover a computationally", "a computationally inferred prediction", "computationally inferred prediction for", "inferred prediction for the", "prediction for the structure", "for the structure of", "the structure of this", "structure of this network", "of this network is", "this network is available", "network is available through", "is available through the", "available through the software", "through the software glycovis", "software glycovis hossler", "glycovis hossler p.", "hossler p. et. al.", "p. et. al. 2006", "et. al. 2006 .", "n glycans are further modified", "glycans are further modified after", "are further modified after the", "further modified after the commitment", "modified after the commitment to", "after the commitment to complex", "the commitment to complex or", "commitment to complex or hybrid", "to complex or hybrid n", "complex or hybrid n glycans.", "or hybrid n glycans. the", "hybrid n glycans. the exact", "n glycans. the exact structure", "glycans. the exact structure of", "the exact structure of the", "exact structure of the network", "structure of the network of", "of the network of metabolic", "the network of metabolic reactions", "network of metabolic reactions involved", "of metabolic reactions involved is", "metabolic reactions involved is complex", "reactions involved is complex and", "involved is complex and not", "is complex and not yet", "complex and not yet validated", "and not yet validated experimentally.", "not yet validated experimentally. here", "yet validated experimentally. here we", "validated experimentally. here we will", "experimentally. here we will show", "here we will show a", "we will show a generic", "will show a generic reaction", "show a generic reaction for", "a generic reaction for each", "generic reaction for each of", "reaction for each of the", "for each of the genes", "each of the genes known", "of the genes known to", "the genes known to be", "genes known to be involved", "known to be involved in", "to be involved in n", "be involved in n glycosylation.
              for", "involved in n glycosylation.
              for a", "in n glycosylation.
              for a better", "n glycosylation.
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              for a better annotation of", "a better annotation of the", "better annotation of the reactions", "annotation of the reactions and", "of the reactions and genes", "the reactions and genes involved", "reactions and genes involved in", "and genes involved in the", "genes involved in the synthesis", "involved in the synthesis of", "in the synthesis of complex", "the synthesis of complex and", "synthesis of complex and hybrid", "of complex and hybrid n", "complex and hybrid n glycans", "and hybrid n glycans we", "hybrid n glycans we recommend", "n glycans we recommend the", "glycans we recommend the glycogene", "we recommend the glycogene database", "the glycogene database ito", "glycogene database ito h.", "database ito h. et", "h. et al 2010", "http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for annotations of", "annotations of genes and", "of genes and the", "genes and the consortium", "and the consortium for functional", "the consortium for functional genomics", "for functional genomics http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp", "genomics http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for", "http://riodb.ibase.aist.go.jp/rcmg/ggdb/textsearch.jsp for annotation of", "for annotation of glycan structures", "annotation of glycan structures and", "of glycan structures and reactions.", "glycan structures and reactions. moreover", "and reactions. moreover a", "reactions. moreover a computationally", "moreover a computationally inferred", "a computationally inferred prediction for", "computationally inferred prediction for the", "inferred prediction for the structure", "prediction for the structure of", "for the structure of this", "the structure of this network", "structure of this network is", "of this network is available", "this network is available through", "network is available through the", "is available through the software", "available through the software glycovis", "the software glycovis hossler", "software glycovis hossler p.", "glycovis hossler p. et.", "hossler p. et. al. 2006", "p. et. al. 2006 ." ] }, { "record_id": "GLY_000594_1_1225", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975578", "r hsa", "hsa 975578", "r hsa 975578" ] }, { "record_id": "GLY_000594_1_1225", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "reactions specific", "specific to", "to the", "the complex", "complex n", "n glycan", "glycan synthesis", "synthesis pathway", "reactions specific to", "specific to the", "to the complex", "the complex n", "complex n glycan", "n glycan synthesis", "glycan synthesis pathway", "reactions specific to the", "specific to the complex", "to the complex n", "the complex n glycan", "complex n glycan synthesis", "n glycan synthesis pathway", "reactions specific to the complex", "specific to the complex n", "to the complex n glycan", "the complex n glycan synthesis", "complex n glycan synthesis 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bases opposite", "of correct bases opposite to", "correct bases opposite to the", "bases opposite to the lesion", "to the lesion b", "lesion b conditional", "b conditional elongation only", "conditional elongation only at the", "elongation only at the sites", "only at the sites where", "at the sites where such", "the sites where such correct", "sites where such correct bases", "where such correct bases are", "such correct bases are inserted", "bases are inserted masutani", "are inserted masutani et", "inserted masutani et al.", "et al. 1999 masutani", "al. 1999 masutani et", "1999 masutani et al.", "masutani et al. 2000 ." ] }, { "record_id": "GLY_000594_1_1230", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "110362", "r hsa", "hsa 110362", "r hsa 110362" ] }, { "record_id": "GLY_000594_1_1230", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "polb dependent", "dependent long", "long patch", "patch base", "base excision", "excision repair", "polb dependent long", "dependent long patch", "long patch base", "patch base excision", "base excision repair", "polb dependent long patch", "dependent long patch base", "long patch base excision", "patch base excision repair", "polb dependent long patch base", "dependent long patch base excision", "long patch base excision repair", "during polb", "parp1 and/or", "and/or parp2", "parp2 is", "is recruited", "recruited to", "to the", "the ber", "ber site", "site along", "along with", "with flap", "flap endonuclease", "endonuclease fen1.", "fen1. parp1", "parp2 and", "and fen1", "fen1 facilitate", "facilitate polb", "polb mediated", "mediated strand", "strand displacement", "displacement synthesis", "synthesis which", "which involves", "involves incorporation", "incorporation of", "of 2", "2 10", "10 nucleotides", "nucleotides at", "at the", "the 3'", "3' end", "end of", "of the", "the apex1", "apex1 created", "created single", "single strand", "strand break", "ssb .", ". after", "after the", "the dna", "dna strand", "synthesis is", "is completed", "completed and", "and the", "the displaced", "displaced strand", "strand is", "is cleaved", "polb recruits", "recruits dna", "dna ligase", "ligase i", "to ligate", "ligate the", "the ssb", "klungland and", "and lindahl", "lindahl 1997", "dimitriadis et", "et al.", "al. 1998", "prasad et", "al. 2001", "lavrik et", "tomkinson et", "ranalli et", "al. 2002", "cistulli et", "al. 2004", "liu et", "al. 2005", "2005 .", "during polb dependent", "repair ber", "parp1 and/or parp2", "and/or parp2 is", "parp2 is recruited", "is recruited to", "recruited to the", "to the ber", "the ber site", "ber site along", "site along with", "along with flap", "with flap endonuclease", "flap endonuclease fen1.", "endonuclease fen1. parp1", "fen1. parp1 and/or", "and/or parp2 and", "parp2 and fen1", "and fen1 facilitate", "fen1 facilitate polb", "facilitate polb mediated", "polb mediated strand", "mediated strand displacement", "strand displacement synthesis", "displacement synthesis which", "synthesis which involves", "which involves incorporation", "involves incorporation of", "incorporation of 2", "of 2 10", "2 10 nucleotides", "10 nucleotides at", "nucleotides at the", "at the 3'", "the 3' end", "3' end of", "end of the", "of the apex1", "the apex1 created", "apex1 created single", "created single strand", "single strand break", "break ssb", "ssb . after", ". after the", "after the dna", "the dna strand", "dna strand displacement", "displacement synthesis is", "synthesis is completed", "is completed and", "completed and the", "and the displaced", "the displaced strand", "displaced strand is", "strand is cleaved", "cleaved polb", "polb recruits dna", "recruits dna ligase", "dna ligase i", "i lig1", "lig1 to", "to ligate the", "ligate the ssb", "ssb klungland", "klungland and lindahl", "and lindahl 1997", "1997 dimitriadis", "dimitriadis et al.", "et al. 1998", "1998 prasad", "prasad et al.", "et al. 2001", "2001 lavrik", "lavrik et al.", "2001 tomkinson", "tomkinson et al.", "2001 ranalli", "ranalli et al.", "et al. 2002", "2002 cistulli", "cistulli et al.", "et al. 2004", "2004 liu", "liu et al.", "et al. 2005", "al. 2005 .", "during polb dependent long", "excision repair ber", "ber parp1", "parp1 and/or parp2 is", "and/or parp2 is recruited", "parp2 is recruited to", "is recruited to the", "recruited to the ber", "to the ber site", "the ber site along", "ber site along with", "site along with flap", "along with flap endonuclease", "with flap endonuclease fen1.", "flap endonuclease fen1. parp1", "endonuclease fen1. parp1 and/or", "fen1. parp1 and/or parp2", "parp1 and/or parp2 and", "and/or parp2 and fen1", "parp2 and fen1 facilitate", "and fen1 facilitate polb", "fen1 facilitate polb mediated", "facilitate polb mediated strand", "polb mediated strand displacement", "mediated strand displacement synthesis", "strand displacement synthesis which", "displacement synthesis which involves", "synthesis which involves incorporation", "which involves incorporation of", "involves incorporation of 2", "incorporation of 2 10", "of 2 10 nucleotides", "2 10 nucleotides at", "10 nucleotides at the", "nucleotides at the 3'", "at the 3' end", "the 3' end of", "3' end of the", "end of the apex1", "of the apex1 created", "the apex1 created single", "apex1 created single strand", "created single strand break", "strand break ssb", "break ssb .", "ssb . after the", ". after the dna", "after the dna strand", "the dna strand displacement", "dna strand displacement synthesis", "strand displacement synthesis is", "displacement synthesis is completed", "synthesis is completed and", "is completed and the", "completed and the displaced", "and the displaced strand", "the displaced strand is", "displaced strand is cleaved", "is cleaved polb", "cleaved polb recruits", "polb recruits dna ligase", "recruits dna ligase i", "ligase i lig1", "lig1 to ligate", "to ligate the ssb", "the ssb klungland", "ssb klungland and", "klungland and lindahl 1997", "lindahl 1997 dimitriadis", "1997 dimitriadis et", "dimitriadis et al. 1998", "al. 1998 prasad", "1998 prasad et", "prasad et al. 2001", "al. 2001 lavrik", "2001 lavrik et", "lavrik et al. 2001", "al. 2001 tomkinson", "2001 tomkinson et", "tomkinson et al. 2001", "al. 2001 ranalli", "2001 ranalli et", "ranalli et al. 2002", "al. 2002 cistulli", "2002 cistulli et", "cistulli et al. 2004", "al. 2004 liu", "2004 liu et", "liu et al. 2005", "et al. 2005 .", "during polb dependent long patch", "base excision repair ber", "ber parp1 and/or", "parp1 and/or parp2 is recruited", "and/or parp2 is recruited to", "parp2 is recruited to the", "is recruited to the ber", "recruited to the ber site", "to the ber site along", "the ber site along with", "ber site along with flap", "site along with flap endonuclease", "along with flap endonuclease fen1.", "with flap endonuclease fen1. parp1", "flap endonuclease fen1. parp1 and/or", "endonuclease fen1. parp1 and/or parp2", "fen1. parp1 and/or parp2 and", "parp1 and/or parp2 and fen1", "and/or parp2 and fen1 facilitate", "parp2 and fen1 facilitate polb", "and fen1 facilitate polb mediated", "fen1 facilitate polb mediated strand", "facilitate polb mediated strand displacement", "polb mediated strand displacement synthesis", "mediated strand displacement synthesis which", "strand displacement synthesis which involves", "displacement synthesis which involves incorporation", "synthesis which involves incorporation of", "which involves incorporation of 2", "involves incorporation of 2 10", "incorporation of 2 10 nucleotides", "of 2 10 nucleotides at", "2 10 nucleotides at the", "10 nucleotides at the 3'", "nucleotides at the 3' end", "at the 3' end of", "the 3' end of the", "3' end of the apex1", "end of the apex1 created", "of the apex1 created single", "the apex1 created single strand", "apex1 created single strand break", "single strand break ssb", "strand break ssb .", "break ssb . after", "ssb . after the dna", ". after the dna strand", "after the dna strand displacement", "the dna strand displacement synthesis", "dna strand displacement synthesis is", "strand displacement synthesis is completed", "displacement synthesis is completed and", "synthesis is completed and the", "is completed and the displaced", "completed and the displaced strand", "and the displaced strand is", "the displaced strand is cleaved", "strand is cleaved polb", "is cleaved polb recruits", "cleaved polb recruits dna", "polb recruits dna ligase i", "dna ligase i lig1", "i lig1 to", "lig1 to ligate the", "ligate the ssb klungland", "the ssb klungland and", "ssb klungland and lindahl", "and lindahl 1997 dimitriadis", "lindahl 1997 dimitriadis et", "1997 dimitriadis et al.", "et al. 1998 prasad", "al. 1998 prasad et", "1998 prasad et al.", "et al. 2001 lavrik", "al. 2001 lavrik et", "2001 lavrik et al.", "et al. 2001 tomkinson", "al. 2001 tomkinson et", "2001 tomkinson et al.", "et al. 2001 ranalli", "al. 2001 ranalli et", "2001 ranalli et al.", "et al. 2002 cistulli", "al. 2002 cistulli et", "2002 cistulli et al.", "et al. 2004 liu", "al. 2004 liu et", "2004 liu et al.", "liu et al. 2005 ." ] }, { "record_id": "GLY_000594_1_1231", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "110373", "r hsa", "hsa 110373", "r hsa 110373" ] }, { "record_id": "GLY_000594_1_1231", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of ap", "ap sites", "sites via", "via the", "the multiple", "multiple nucleotide", "nucleotide patch", "patch replacement", "replacement pathway", "resolution of ap", "of ap sites", "ap sites via", "sites via the", "via the multiple", "the multiple nucleotide", "multiple nucleotide patch", "nucleotide patch replacement", "patch replacement pathway", "resolution of ap sites", "of ap sites via", "ap sites via the", "sites via the multiple", "via the multiple nucleotide", "the multiple nucleotide patch", "multiple nucleotide patch replacement", "nucleotide patch replacement pathway", "resolution of ap sites via", "of ap sites via the", "ap sites via the multiple", "sites via the multiple nucleotide", "via the multiple nucleotide patch", "the multiple nucleotide patch replacement", "multiple nucleotide patch replacement pathway", "while the", "the single", "single nucleotide", "nucleotide replacement", "pathway appears", "appears to", "to facilitate", "facilitate the", "the repair", "repair of", "of most", "most damaged", "damaged bases", "an alternative", "alternative ber", "ber pathway", "pathway is", "is evoked", "evoked when", "when the", "the structure", "structure of", "of the", "the 5'", "5' terminal", "terminal sugar", "sugar phosphate", "phosphate is", "is such", "such that", "that it", "it cannot", "cannot be", "be cleaved", "cleaved through", "through the", "the ap", "ap lyase", "lyase activity", "activity of", "of dna", "dna polymerase", "polymerase beta", "polb .", ". under", "under these", "these circumstances", "a short", "short stretch", "stretch of", "of residues", "residues containing", "containing the", "the abasic", "abasic site", "site is", "is excised", "excised and", "and replaced", "dianov et", "et al.", "1999 .", ". following", "following dna", "dna glycosylase", "glycosylase mediated", "mediated cleavage", "cleavage of", "the damaged", "damaged base", "the endonuclease", "endonuclease apex1", "apex1 is", "is recruited", "recruited to", "to the", "the site", "site of", "of damage", "damage where", "where it", "it cleaves", "cleaves the", "5' side", "side of", "abasic deoxyribose", "deoxyribose residue", "as in", "in the", "replacement pathway.", "pathway. however", "polb then", "then synthesizes", "synthesizes the", "the first", "first replacement", "replacement residue", "residue without", "without prior", "prior cleavage", "hence displacing", "displacing this", "this entity.", "entity. long", "long patch", "patch ber", "ber can", "can be", "be completed", "completed by", "by continued", "continued polb", "polb mediated", "mediated dna", "dna strand", "strand displacement", "displacement synthesis", "synthesis in", "the presence", "presence of", "of parp1", "parp1 or", "or parp2", "fen1 and", "and dna", "dna ligase", "ligase i", "prasad et", "al. 2001", "2001 .", ". when", "the pcna", "pcna containing", "containing replication", "replication complex", "complex is", "is available", "as is", "is the", "the case", "case with", "with cells", "cells in", "the s", "s phase", "phase of", "the cell", "cell cycle", "synthesis is", "is catalyzed", "catalyzed by", "by dna", "polymerase delta", "or dna", "polymerase epsilon", "of pcna", "and lig1", "klungland and", "and lindahl", "lindahl 1997", "dianova et", ". in", "in both", "both polb", "polb dependent", "dependent and", "and pcna", "pcna dependent", "dependent dna", "dna displacement", "the displaced", "displaced dna", "strand containing", "abasic sugar", "phosphate creates", "creates a", "a flap", "flap structure", "structure that", "that is", "is recognized", "recognized and", "and cleaved", "cleaved by", "by the", "the flap", "flap endonuclease", "endonuclease fen1.", "fen1. the", "the replacement", "replacement residues", "residues added", "added by", "by polb", "polb or", "or pold/pole", "pold/pole are", "are then", "then ligated", "ligated by", "the dna", "matsumoto et", "1999 .

              ", "while the single", "the single nucleotide", "single nucleotide replacement", "nucleotide replacement pathway", "replacement pathway appears", "pathway appears to", "appears to facilitate", "to facilitate the", "facilitate the repair", "the repair of", "repair of most", "of most damaged", "most damaged bases", "bases an", "an alternative ber", "alternative ber pathway", "ber pathway is", "pathway is evoked", "is evoked when", "evoked when the", "when the structure", "the structure of", "structure of the", "of the 5'", "the 5' terminal", "5' terminal sugar", "terminal sugar phosphate", "sugar phosphate is", "phosphate is such", "is such that", "such that it", "that it cannot", "it cannot be", "cannot be cleaved", "be cleaved through", "cleaved through the", "through the ap", "the ap lyase", "ap lyase activity", "lyase activity of", "activity of dna", "of dna polymerase", "dna polymerase beta", "beta polb", "polb . under", ". under these", "under these circumstances", "circumstances a", "a short stretch", "short stretch of", "stretch of residues", "of residues containing", "residues containing the", "containing the abasic", "the abasic site", "abasic site is", "site is excised", "is excised and", "excised and replaced", "replaced dianov", "dianov et al.", "al. 1999", "1999 . following", ". following dna", "following dna glycosylase", "dna glycosylase mediated", "glycosylase mediated cleavage", "mediated cleavage of", "cleavage of the", "of the damaged", "the damaged base", "base the", "the endonuclease apex1", "endonuclease apex1 is", "apex1 is recruited", "is recruited to", "recruited to the", "to the site", "the site of", "site of damage", "of damage where", "damage where it", "where it cleaves", "it cleaves the", "cleaves the 5'", "the 5' side", "5' side of", "side of the", "of the abasic", "the abasic deoxyribose", "abasic deoxyribose residue", "residue as", "as in the", "in the single", "nucleotide replacement pathway.", "replacement pathway. however", "however polb", "polb then synthesizes", "then synthesizes the", "synthesizes the first", "the first replacement", "first replacement residue", "replacement residue without", "residue without prior", "without prior cleavage", "prior cleavage of", "phosphate hence", "hence displacing this", "displacing this entity.", "this entity. long", "entity. long patch", "long patch ber", "patch ber can", "ber can be", "can be completed", "be completed by", "completed by continued", "by continued polb", "continued polb mediated", "polb mediated dna", "mediated dna strand", "dna strand displacement", "strand displacement synthesis", "displacement synthesis in", "synthesis in the", "in the presence", "the presence of", "presence of parp1", "of parp1 or", "parp1 or parp2", "parp2 fen1", "fen1 and dna", "and dna ligase", "dna ligase i", "i lig1", "prasad et al.", "et al. 2001", "al. 2001 .", "2001 . when", ". when the", "when the pcna", "the pcna containing", "pcna containing replication", "containing replication complex", "replication complex is", "complex is available", "available as", "as is the", "is the case", "the case with", "case with cells", "with cells in", "cells in the", "in the s", "the s phase", "s phase of", "phase of the", "of the cell", "the cell cycle", "cycle dna", "displacement synthesis is", "synthesis is catalyzed", "is catalyzed by", "catalyzed by dna", "by dna polymerase", "dna polymerase delta", "delta pold", "pold or", "or dna polymerase", "dna polymerase epsilon", "epsilon pole", "pole complexes", "complexes in", "presence of pcna", "pcna rpa", "rpa rfc", "rfc apex1", "apex1 fen1", "fen1 and lig1", "lig1 klungland", "klungland and lindahl", "and lindahl 1997", "1997 dianova", "dianova et al.", "2001 . in", ". in both", "in both polb", "both polb dependent", "polb dependent and", "dependent and pcna", "and pcna dependent", "pcna dependent dna", "dependent dna displacement", "dna displacement synthesis", "synthesis the", "the displaced dna", "displaced dna strand", "dna strand containing", "strand containing the", "the abasic sugar", "abasic sugar phosphate", "sugar phosphate creates", "phosphate creates a", "creates a flap", "a flap structure", "flap structure that", "structure that is", "that is recognized", "is recognized and", "recognized and cleaved", "and cleaved by", "cleaved by the", "by the flap", "the flap endonuclease", "flap endonuclease fen1.", "endonuclease fen1. the", "fen1. the replacement", "the replacement residues", "replacement residues added", "residues added by", "added by polb", "by polb or", "polb or pold/pole", "or pold/pole are", "pold/pole are then", "are then ligated", "then ligated by", "ligated by the", "by the dna", "the dna ligase", "1997 matsumoto", "matsumoto et al.", "while the single nucleotide", "the single nucleotide replacement", "single nucleotide replacement pathway", "nucleotide replacement pathway appears", "replacement pathway appears to", "pathway appears to facilitate", "appears to facilitate the", "to facilitate the repair", "facilitate the repair of", "the repair of most", "repair of most damaged", "of most damaged bases", "damaged bases an", "bases an alternative", "an alternative ber pathway", "alternative ber pathway is", "ber pathway is evoked", "pathway is evoked when", "is evoked when the", "evoked when the structure", "when the structure of", "the structure of the", "structure of the 5'", "of the 5' terminal", "the 5' terminal sugar", "5' terminal sugar phosphate", "terminal sugar phosphate is", "sugar phosphate is such", "phosphate is such that", "is such that it", "such that it cannot", "that it cannot be", "it cannot be cleaved", "cannot be cleaved through", "be cleaved through the", "cleaved through the ap", "through the ap lyase", "the ap lyase activity", "ap lyase activity of", "lyase activity of dna", "activity of dna polymerase", "of dna polymerase beta", "polymerase beta polb", "beta polb .", "polb . under these", ". under these circumstances", "these circumstances a", "circumstances a short", "a short stretch of", "short stretch of residues", "stretch of residues containing", "of residues containing the", "residues containing the abasic", "containing the abasic site", "the abasic site is", "abasic site is excised", "site is excised and", "is excised and replaced", "and replaced dianov", "replaced dianov et", "et al. 1999", "al. 1999 .", "1999 . following dna", ". following dna glycosylase", "following dna glycosylase mediated", "dna glycosylase mediated cleavage", "glycosylase mediated cleavage of", "mediated cleavage of the", "cleavage of the damaged", "of the damaged base", "damaged base the", "base the endonuclease", "the endonuclease apex1 is", "endonuclease apex1 is recruited", "apex1 is recruited to", "is recruited to the", "recruited to the site", "to the site of", "the site of damage", "site of damage where", "of damage where it", "damage where it cleaves", "where it cleaves the", "it cleaves the 5'", "cleaves the 5' side", "the 5' side of", "5' side of the", "side of the abasic", "of the abasic deoxyribose", "the abasic deoxyribose residue", "deoxyribose residue as", "residue as in", "as in the single", "in the single nucleotide", "single nucleotide replacement pathway.", "nucleotide replacement pathway. however", "pathway. however polb", "however polb then", "polb then synthesizes the", "then synthesizes the first", "synthesizes the first replacement", "the first replacement residue", "first replacement residue without", "replacement residue without prior", "residue without prior cleavage", "without prior cleavage of", "prior cleavage of the", "cleavage of the 5'", "sugar phosphate hence", "phosphate hence displacing", "hence displacing this entity.", "displacing this entity. long", "this entity. long patch", "entity. long patch ber", "long patch ber can", "patch ber can be", "ber can be completed", "can be completed by", "be completed by continued", "completed by continued polb", "by continued polb mediated", "continued polb mediated dna", "polb mediated dna strand", "mediated dna strand displacement", "dna strand displacement synthesis", "strand displacement synthesis in", "displacement synthesis in the", "synthesis in the presence", "in the presence of", "the presence of parp1", "presence of parp1 or", "of parp1 or parp2", "or parp2 fen1", "parp2 fen1 and", "fen1 and dna ligase", "and dna ligase i", "ligase i lig1", "lig1 prasad", "prasad et al. 2001", "et al. 2001 .", "al. 2001 . when", "2001 . when the", ". when the pcna", "when the pcna containing", "the pcna containing replication", "pcna containing replication complex", "containing replication complex is", "replication complex is available", "is available as", "available as is", "as is the case", "is the case with", "the case with cells", "case with cells in", "with cells in the", "cells in the s", "in the s phase", "the s phase of", "s phase of the", "phase of the cell", "of the cell cycle", "cell cycle dna", "cycle dna strand", "strand displacement synthesis is", "displacement synthesis is catalyzed", "synthesis is catalyzed by", "is catalyzed by dna", "catalyzed by dna polymerase", "by dna polymerase delta", "polymerase delta pold", "pold or dna", "or dna polymerase epsilon", "polymerase epsilon pole", "complexes in the", "the presence of pcna", "of pcna rpa", "apex1 fen1 and", "and lig1 klungland", "lig1 klungland and", "klungland and lindahl 1997", "lindahl 1997 dianova", "1997 dianova et", "dianova et al. 2001", "al. 2001 . in", "2001 . in both", ". in both polb", "in both polb dependent", "both polb dependent and", "polb dependent and pcna", "dependent and pcna dependent", "and pcna dependent dna", "pcna dependent dna displacement", "dependent dna displacement synthesis", "displacement synthesis the", "synthesis the displaced", "the displaced dna strand", "displaced dna strand containing", "dna strand containing the", "strand containing the abasic", "containing the abasic sugar", "the abasic sugar phosphate", "abasic sugar phosphate creates", "sugar phosphate creates a", "phosphate creates a flap", "creates a flap structure", "a flap structure that", "flap structure that is", "structure that is recognized", "that is recognized and", "is recognized and cleaved", "recognized and cleaved by", "and cleaved by the", "cleaved by the flap", "by the flap endonuclease", "the flap endonuclease fen1.", "flap endonuclease fen1. the", "endonuclease fen1. the replacement", "fen1. the replacement residues", "the replacement residues added", "replacement residues added by", "residues added by polb", "added by polb or", "by polb or pold/pole", "polb or pold/pole are", "or pold/pole are then", "pold/pole are then ligated", "are then ligated by", "then ligated by the", "ligated by the dna", "by the dna ligase", "the dna ligase i", "1997 matsumoto et", "al. 1999 .

              ", "while the single nucleotide replacement", "the single nucleotide replacement pathway", "single nucleotide replacement pathway appears", "nucleotide replacement pathway appears to", "replacement pathway appears to facilitate", "pathway appears to facilitate the", "appears to facilitate the repair", "to facilitate the repair of", "facilitate the repair of most", "the repair of most damaged", "repair of most damaged bases", "most damaged bases an", "damaged bases an alternative", "bases an alternative ber", "an alternative ber pathway is", "alternative ber pathway is evoked", "ber pathway is evoked when", "pathway is evoked when the", "is evoked when the structure", "evoked when the structure of", "when the structure of the", "the structure of the 5'", "structure of the 5' terminal", "of the 5' terminal sugar", "the 5' terminal sugar phosphate", "5' terminal sugar phosphate is", "terminal sugar phosphate is such", "sugar phosphate is such that", "phosphate is such that it", "is such that it cannot", "such that it cannot be", "that it cannot be cleaved", "it cannot be cleaved through", "cannot be cleaved through the", "be cleaved through the ap", "cleaved through the ap lyase", "through the ap lyase activity", "the ap lyase activity of", "ap lyase activity of dna", "lyase activity of dna polymerase", "activity of dna polymerase beta", "dna polymerase beta polb", "polymerase beta polb .", "beta polb . under", "polb . under these circumstances", "under these circumstances a", "these circumstances a short", "circumstances a short stretch", "a short stretch of residues", "short stretch of residues containing", "stretch of residues containing the", "of residues containing the abasic", "residues containing the abasic site", "containing the abasic site is", "the abasic site is excised", "abasic site is excised and", "site is excised and replaced", "excised and replaced dianov", "and replaced dianov et", "replaced dianov et al.", "dianov et al. 1999", "et al. 1999 .", "al. 1999 . following", "1999 . following dna glycosylase", ". following dna glycosylase mediated", "following dna glycosylase mediated cleavage", "dna glycosylase mediated cleavage of", "glycosylase mediated cleavage of the", "mediated cleavage of the damaged", "cleavage of the damaged base", "the damaged base the", "damaged base the endonuclease", "base the endonuclease apex1", "the endonuclease apex1 is recruited", "endonuclease apex1 is recruited to", "apex1 is recruited to the", "is recruited to the site", "recruited to the site of", "to the site of damage", "the site of damage where", "site of damage where it", "of damage where it cleaves", "damage where it cleaves the", "where it cleaves the 5'", "it cleaves the 5' side", "cleaves the 5' side of", "the 5' side of the", "5' side of the abasic", "side of the abasic deoxyribose", "of the abasic deoxyribose residue", "abasic deoxyribose residue as", "deoxyribose residue as in", "residue as in the", "as in the single nucleotide", "in the single nucleotide replacement", "the single nucleotide replacement pathway.", "single nucleotide replacement pathway. however", "replacement pathway. however polb", "pathway. however polb then", "however polb then synthesizes", "polb then synthesizes the first", "then synthesizes the first replacement", "synthesizes the first replacement residue", "the first replacement residue without", "first replacement residue without prior", "replacement residue without prior cleavage", "residue without prior cleavage of", "without prior cleavage of the", "prior cleavage of the 5'", "cleavage of the 5' terminal", "terminal sugar phosphate hence", "sugar phosphate hence displacing", "phosphate hence displacing this", "hence displacing this entity. long", "displacing this entity. long patch", "this entity. long patch ber", "entity. long patch ber can", "long patch ber can be", "patch ber can be completed", "ber can be completed by", "can be completed by continued", "be completed by continued polb", "completed by continued polb mediated", "by continued polb mediated dna", "continued polb mediated dna strand", "polb mediated dna strand displacement", "mediated dna strand displacement synthesis", "dna strand displacement synthesis in", "strand displacement synthesis in the", "displacement synthesis in the presence", "synthesis in the presence of", "in the presence of parp1", "the presence of parp1 or", "presence of parp1 or parp2", "parp1 or parp2 fen1", "or parp2 fen1 and", "parp2 fen1 and dna", "fen1 and dna ligase i", "dna ligase i lig1", "lig1 prasad et", "prasad et al. 2001 .", "et al. 2001 . when", "al. 2001 . when the", "2001 . when the pcna", ". when the pcna containing", "when the pcna containing replication", "the pcna containing replication complex", "pcna containing replication complex is", "containing replication complex is available", "complex is available as", "is available as is", "available as is the", "as is the case with", "is the case with cells", "the case with cells in", "case with cells in the", "with cells in the s", "cells in the s phase", "in the s phase of", "the s phase of the", "s phase of the cell", "phase of the cell cycle", "the cell cycle dna", "cell cycle dna strand", "cycle dna strand displacement", "dna strand displacement synthesis is", "strand displacement synthesis is catalyzed", "displacement synthesis is catalyzed by", "synthesis is catalyzed by dna", "is catalyzed by dna polymerase", "catalyzed by dna polymerase delta", "dna polymerase delta pold", "delta pold or", "pold or dna polymerase", "dna polymerase epsilon pole", "epsilon pole complexes", "pole complexes in", "complexes in the presence", "in the presence of pcna", "presence of pcna rpa", "pcna rpa rfc", "rpa rfc apex1", "rfc apex1 fen1", "apex1 fen1 and lig1", "fen1 and lig1 klungland", "and lig1 klungland and", "lig1 klungland and lindahl", "and lindahl 1997 dianova", "lindahl 1997 dianova et", "1997 dianova et al.", "dianova et al. 2001 .", "et al. 2001 . in", "al. 2001 . in both", "2001 . in both polb", ". in both polb dependent", "in both polb dependent and", "both polb dependent and pcna", "polb dependent and pcna dependent", "dependent and pcna dependent dna", "and pcna dependent dna displacement", "pcna dependent dna displacement synthesis", "dna displacement synthesis the", "displacement synthesis the displaced", "synthesis the displaced dna", "the displaced dna strand containing", "displaced dna strand containing the", "dna strand containing the abasic", "strand containing the abasic sugar", "containing the abasic sugar phosphate", "the abasic sugar phosphate creates", "abasic sugar phosphate creates a", "sugar phosphate creates a flap", "phosphate creates a flap structure", "creates a flap structure that", "a flap structure that is", "flap structure that is recognized", "structure that is recognized and", "that is recognized and cleaved", "is recognized and cleaved by", "recognized and cleaved by the", "and cleaved by the flap", "cleaved by the flap endonuclease", "by the flap endonuclease fen1.", "the flap endonuclease fen1. the", "flap endonuclease fen1. the replacement", "endonuclease fen1. the replacement residues", "fen1. the replacement residues added", "the replacement residues added by", "replacement residues added by polb", "residues added by polb or", "added by polb or pold/pole", "by polb or pold/pole are", "polb or pold/pole are then", "or pold/pole are then ligated", "pold/pole are then ligated by", "are then ligated by the", "then ligated by the dna", "ligated by the dna ligase", "by the dna ligase i", "lindahl 1997 matsumoto", "1997 matsumoto et al.", "matsumoto et al. 1999", "et al. 1999 .

              " ] }, { "record_id": "GLY_000594_1_1232", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "110381", "r hsa", "hsa 110381", "r hsa 110381" ] }, { "record_id": "GLY_000594_1_1232", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of ap", "ap sites", "sites via", "via the", "the single", "single nucleotide", "nucleotide replacement", "replacement pathway", "resolution of ap", "of ap sites", "ap sites via", "sites via the", "via the single", "the single nucleotide", "single nucleotide replacement", "nucleotide replacement pathway", "resolution of ap sites", "of ap sites via", "ap sites via the", "sites via the single", "via the single nucleotide", "the single nucleotide replacement", "single nucleotide replacement pathway", "resolution of ap sites via", "of ap sites via the", "ap sites via the single", "sites via the single nucleotide", "via the single nucleotide 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interaction of", "through the interaction of the", "the interaction of the sperm", "interaction of the sperm bound", "of the sperm bound protein", "the sperm bound protein izumo", "sperm bound protein izumo and", "bound protein izumo and the", "protein izumo and the ooctye", "izumo and the ooctye cd9", "and the ooctye cd9 membrane", "the ooctye cd9 membrane protein." ] }, { "record_id": "GLY_000594_1_1247", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1362300", "r hsa", "hsa 1362300", "r hsa 1362300" ] }, { "record_id": "GLY_000594_1_1247", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcription of", "of e2f", "e2f targets", "targets under", "under negative", "negative control", "control by", "by p107", "and p130", "in complex", "complex with", "with hdac1", "transcription of e2f", "of e2f targets", "e2f targets under", "targets under negative", "under negative control", "negative 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"al. 2012 .", "2012 . fe", ". fe s", "fe s protein", "s protein biogenesis", "protein biogenesis in", "biogenesis in the", "in the mitochondrial", "the mitochondrial matrix", "mitochondrial matrix involves", "matrix involves the", "involves the iron", "the iron sulfur", "cluster isc", "isc assembly", "assembly machinery. ferrous", "machinery. ferrous iron", "ferrous iron is", "iron is transported", "is transported across", "transported across the", "across the inner", "the inner mitochondrial", "inner mitochondrial membrane", "mitochondrial membrane into", "membrane into the", "into the mitochondrial", "mitochondrial matrix by", "matrix by mitoferrin", "by mitoferrin 1", "1 slc25a37", "slc25a37 and", "and mitoferrin 2", "2 slc25a28", ". mitoferrin", "mitoferrin 1 is", "1 is enriched", "is enriched in", "enriched in erythroid", "in erythroid cells", "erythroid cells while", "cells while mitoferrin", "while mitoferrin 2", "mitoferrin 2 is", "2 is ubiquitous.", "ubiquitous. frataxin", 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desulfurase", "for desulfurase activity.", "desulfurase activity. frataxin", "activity. frataxin binds", "frataxin binds to", "binds to a", "to a complex", "a complex containing", "complex containing nfs1", "nfs1 isd11", "isd11 and", "and iscu and", "iscu and is", "and is proposed", "is proposed to", "proposed to function", "to function as", "function as an", "as an iron", "an iron donor", "iron donor to", "donor to iscu", "to iscu or", "iscu or as", "or as an", "as an allosteric", "an allosteric switch", "allosteric switch that", "switch that activates", "that activates sulfur", "activates sulfur transfer", "sulfur transfer and", "transfer and fe", "and fe s", "fe s cluster", "s cluster assembly", "assembly tsai", "tsai and barondeau", "and barondeau 2010", "barondeau 2010 .", "2010 . cluster", ". cluster formation", "cluster formation also", "formation also involves", "also involves the", "involves the electron", "the electron transfer", "electron transfer chain", "transfer chain 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involve the", "involve the function", "function of isca1", "isca1 isca2", "isca2 and", "and iba57. the", "iba57. the clusters", "the clusters are", "clusters are transferred", "are transferred to", "transferred to apo", "to apo enzymes", "apo enzymes such", "enzymes such as", "such as the", "as the respiratory", "the respiratory complexes", "complexes aconitase", "aconitase and", "and lipoate synthase", "lipoate synthase through", "synthase through dedicated", "through dedicated targeting", "dedicated targeting factors", "targeting factors such", "factors such as", "such as ind1", "ind1 nfu1", "nfu1 and", "iron sulfur fe", "sulfur fe s", "fe s proteins", "s proteins are", "proteins are localized in", "are localized in the", "localized in the cytosol", "the cytosol nucleus", "nucleus and mitochondria", "and mitochondria of mammalian", "mitochondria of mammalian cells", "mammalian cells reviewed", "cells reviewed in", "reviewed in stemmler et", "in stemmler et al.", "stemmler et al. 2010", "al. 2010 rouault", "2010 rouault 2012", "rouault 2012 bandyopadhyay", "2012 bandyopadhyay et", "bandyopadhyay et al. 2008", "al. 2008 lill", "2008 lill 2009", "lill 2009 lill", "2009 lill et", "lill et al. 2012", "et al. 2012 .", "al. 2012 . fe", "2012 . fe s", ". fe s protein", "fe s protein biogenesis", "s protein biogenesis in", "protein biogenesis in the", "biogenesis in the mitochondrial", "in the mitochondrial matrix", "the mitochondrial matrix involves", "mitochondrial matrix involves the", "matrix involves the iron", "involves the iron sulfur", "the iron sulfur cluster", "sulfur cluster isc", "isc assembly machinery.", "assembly machinery. ferrous iron", "machinery. ferrous iron is", "ferrous iron is transported", "iron is transported across", "is transported across the", "transported across the inner", "across the inner mitochondrial", "the inner mitochondrial membrane", "inner mitochondrial membrane into", "mitochondrial membrane into the", "membrane into the 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isd11", "subcomplex with isd11 provides", "with isd11 provides the", "isd11 provides the sulfur", "provides the sulfur by", "the sulfur by converting", "sulfur by converting cyteine", "by converting cyteine into", "converting cyteine into alanine", "cyteine into alanine and", "into alanine and forming", "alanine and forming a", "and forming a persulfide", "forming a persulfide which", "a persulfide which is", "persulfide which is used", "which is used for", "is used for cluster", "used for cluster formation", "for cluster formation on", "cluster formation on iscu", "on iscu the", "iscu the scaffold", "the scaffold protein. interaction", "scaffold protein. interaction between", "protein. interaction between nfs1", "interaction between nfs1 and", "between nfs1 and isd11", "nfs1 and isd11 is", "and isd11 is necessary", "isd11 is necessary for", "is necessary for desulfurase", "necessary for desulfurase activity.", "for desulfurase activity. frataxin", "desulfurase activity. frataxin binds", "activity. frataxin binds to", "frataxin binds to a", "binds to a complex", "to a complex containing", "a complex containing nfs1", "containing nfs1 isd11", "isd11 and iscu", "and iscu and is", "iscu and is proposed", "and is proposed to", "is proposed to function", "proposed to function as", "to function as an", "function as an iron", "as an iron donor", "an iron donor to", "iron donor to iscu", "donor to iscu or", "to iscu or as", "iscu or as an", "or as an allosteric", "as an allosteric switch", "an allosteric switch that", "allosteric switch that activates", "switch that activates sulfur", "that activates sulfur transfer", "activates sulfur transfer and", "sulfur transfer and fe", "transfer and fe s", "and fe s cluster", "fe s cluster assembly", "cluster assembly tsai", "assembly tsai and", "tsai and barondeau 2010", "and barondeau 2010 .", "barondeau 2010 . cluster", "2010 . cluster formation", ". cluster formation also", "cluster formation also involves", "formation also involves the", "also involves the electron", "involves the electron transfer", "the electron transfer chain", "electron transfer chain ferredoxin", "transfer chain ferredoxin reductase", "chain ferredoxin reductase and", "ferredoxin reductase and ferredoxin.", "reductase and ferredoxin. iscu", "and ferredoxin. iscu initially", "ferredoxin. iscu initially forms", "iscu initially forms clusters", "initially forms clusters containing", "forms clusters containing 2", "clusters containing 2 iron", "containing 2 iron atoms", "2 iron atoms and", "iron atoms and 2", "atoms and 2 sulfur", "and 2 sulfur atoms", "atoms 2fe", "2fe 2s clusters", "2s clusters .", "clusters . they are", ". they are released", "they are released by", "are released by the", "released by the function", "by the function of", "the function of hsp70", "function of hsp70 hsc20", "of hsp70 hsc20 chaperones", "hsp70 hsc20 chaperones and", "hsc20 chaperones and the", "chaperones and the monothiol", "and the monothiol glutaredoxin", "the monothiol glutaredoxin glrx5", "monothiol glutaredoxin glrx5 and", "glutaredoxin glrx5 and used", "glrx5 and used for", "and used for assembly", "used for assembly of", "assembly of 2fe", "of 2fe 2s", "2fe 2s proteins.", "2s proteins. assembly", "proteins. assembly of larger", "assembly of larger clusters", "of larger clusters such", "larger clusters such as", "such as 4fe", "as 4fe 4s", "4fe 4s clusters", "4s clusters may", "clusters may involve the", "may involve the function", "involve the function of", "the function of isca1", "of isca1 isca2", "isca2 and iba57.", "and iba57. the clusters", "iba57. the clusters are", "the clusters are transferred", "clusters are transferred to", "are transferred to apo", "transferred to apo enzymes", "to apo enzymes such", "apo enzymes such as", "enzymes such as the", "such as the respiratory", "as the respiratory complexes", "respiratory complexes aconitase", "aconitase and lipoate", "and lipoate synthase through", "lipoate synthase through dedicated", "synthase through dedicated targeting", "through dedicated targeting factors", "dedicated targeting factors such", "targeting factors such as", "factors such as ind1", "as ind1 nfu1", "nfu1 and bola3.", "iron sulfur fe s", "fe s proteins are", "s proteins are localized", "proteins are localized in the", "are localized in the cytosol", "in the cytosol nucleus", "cytosol nucleus and", "nucleus and mitochondria of", "and mitochondria of mammalian cells", "of mammalian cells reviewed", "mammalian cells reviewed in", "cells reviewed in stemmler", "reviewed in stemmler et al.", "in stemmler et al. 2010", "et al. 2010 rouault", "al. 2010 rouault 2012", "rouault 2012 bandyopadhyay et", "2012 bandyopadhyay et al.", "et al. 2008 lill", "al. 2008 lill 2009", "lill 2009 lill et", "2009 lill et al.", "lill et al. 2012 .", "et al. 2012 . fe", "al. 2012 . fe s", "2012 . fe s protein", ". fe s protein biogenesis", "fe s protein biogenesis in", "s protein biogenesis in the", "protein biogenesis in the mitochondrial", "biogenesis in the mitochondrial matrix", "in the mitochondrial matrix involves", "the mitochondrial matrix involves the", "mitochondrial matrix involves the iron", "matrix involves the iron sulfur", "involves the iron sulfur cluster", "iron sulfur cluster isc", "cluster isc assembly", "isc assembly machinery. ferrous", "assembly machinery. ferrous iron is", "machinery. ferrous iron is transported", "ferrous iron is transported across", "iron is transported across the", "is transported across the inner", "transported across the inner mitochondrial", "across the inner mitochondrial membrane", "the inner mitochondrial membrane into", "inner mitochondrial membrane into the", "mitochondrial membrane into the mitochondrial", "membrane into the mitochondrial matrix", "into the mitochondrial matrix by", "the mitochondrial matrix by mitoferrin", "mitochondrial matrix by mitoferrin 1", "by mitoferrin 1 slc25a37", "1 slc25a37 and", "slc25a37 and mitoferrin 2", "and mitoferrin 2 slc25a28", "mitoferrin 2 slc25a28 .", "slc25a28 . mitoferrin 1", ". mitoferrin 1 is", "mitoferrin 1 is enriched in", "1 is enriched in erythroid", "is enriched in erythroid cells", "enriched in erythroid cells while", "in erythroid cells while mitoferrin", "erythroid cells while mitoferrin 2", "cells while mitoferrin 2 is", "while mitoferrin 2 is ubiquitous.", "2 is ubiquitous. frataxin", "is ubiquitous. frataxin binds", "ubiquitous. frataxin binds ferrous", "frataxin binds ferrous iron in", "binds ferrous iron in the", "ferrous iron in the mitochondrial", "iron in the mitochondrial matrix.", "in the mitochondrial matrix. the", "the mitochondrial matrix. the cysteine", "mitochondrial matrix. the cysteine desulfurase", "matrix. the cysteine desulfurase nfs1", "the cysteine desulfurase nfs1 in", "cysteine desulfurase nfs1 in a", "desulfurase nfs1 in a subcomplex", "nfs1 in a subcomplex with", "in a subcomplex with isd11", "a subcomplex with isd11 provides", "subcomplex with isd11 provides the", "with isd11 provides the sulfur", "isd11 provides the sulfur by", "provides the sulfur by converting", "the sulfur by converting cyteine", "sulfur by converting cyteine into", "by converting cyteine into alanine", "converting cyteine into alanine and", "cyteine into alanine and forming", "into alanine and forming a", "alanine and forming a persulfide", "and forming a persulfide which", "forming a persulfide which is", "a persulfide which is used", "persulfide which is used for", "which is used for cluster", "is used for cluster formation", "used for cluster formation on", "for cluster formation on iscu", "formation on iscu the", "on iscu the scaffold", "iscu the scaffold protein.", "the scaffold protein. interaction between", "scaffold protein. interaction between nfs1", "protein. interaction between nfs1 and", "interaction between nfs1 and isd11", "between nfs1 and isd11 is", "nfs1 and isd11 is necessary", "and isd11 is necessary for", "isd11 is necessary for desulfurase", "is necessary for desulfurase activity.", "necessary for desulfurase activity. frataxin", "for desulfurase activity. frataxin binds", "desulfurase activity. frataxin binds to", "activity. frataxin binds to a", "frataxin binds to a complex", "binds to a complex containing", "to a complex containing nfs1", "complex containing nfs1 isd11", "nfs1 isd11 and", "isd11 and iscu and", "and iscu and is proposed", "iscu and is proposed to", "and is proposed to function", "is proposed to function as", "proposed to function as an", "to function as an iron", "function as an iron donor", "as an iron donor to", "an iron donor to iscu", "iron donor to iscu or", "donor to iscu or as", "to iscu or as an", "iscu or as an allosteric", "or as an allosteric switch", "as an allosteric switch that", "an allosteric switch that activates", "allosteric switch that activates sulfur", "switch that activates sulfur transfer", "that activates sulfur transfer and", "activates sulfur transfer and fe", "sulfur transfer and fe s", "transfer and fe s cluster", "and fe s cluster assembly", "s cluster assembly tsai", "cluster assembly tsai and", "assembly tsai and barondeau", "tsai and barondeau 2010 .", "and barondeau 2010 . cluster", "barondeau 2010 . cluster formation", "2010 . cluster formation also", ". cluster formation also involves", "cluster formation also involves the", "formation also involves the electron", "also involves the electron transfer", "involves the electron transfer chain", "the electron transfer chain ferredoxin", "electron transfer chain ferredoxin reductase", "transfer chain ferredoxin reductase and", "chain ferredoxin reductase and ferredoxin.", "ferredoxin reductase and ferredoxin. iscu", "reductase and ferredoxin. iscu initially", "and ferredoxin. iscu initially forms", "ferredoxin. iscu initially forms clusters", "iscu initially forms clusters containing", "initially forms clusters containing 2", "forms clusters containing 2 iron", "clusters containing 2 iron atoms", "containing 2 iron atoms and", "2 iron atoms and 2", "iron atoms and 2 sulfur", "atoms and 2 sulfur atoms", "sulfur atoms 2fe", "atoms 2fe 2s", "2fe 2s clusters .", "2s clusters . they", "clusters . they are released", ". they are released by", "they are released by the", "are released by the function", "released by the function of", "by the function of hsp70", "the function of hsp70 hsc20", "function of hsp70 hsc20 chaperones", "of hsp70 hsc20 chaperones and", "hsp70 hsc20 chaperones and the", "hsc20 chaperones and the monothiol", "chaperones and the monothiol glutaredoxin", "and the monothiol glutaredoxin glrx5", "the monothiol glutaredoxin glrx5 and", "monothiol glutaredoxin glrx5 and used", "glutaredoxin glrx5 and used for", "glrx5 and used for assembly", "and used for assembly of", "for assembly of 2fe", "assembly of 2fe 2s", "2fe 2s proteins. assembly", "2s proteins. assembly of", "proteins. assembly of larger clusters", "assembly of larger clusters such", "of larger clusters such as", "clusters such as 4fe", "such as 4fe 4s", "4fe 4s clusters may", "4s clusters may involve", "clusters may involve the function", "may involve the function of", "involve the function of isca1", "function of isca1 isca2", "isca1 isca2 and", "isca2 and iba57. the", "and iba57. the clusters are", "iba57. the clusters are transferred", "the clusters are transferred to", "clusters are transferred to apo", "are transferred to apo enzymes", "transferred to apo enzymes such", "to apo enzymes such as", "apo enzymes such as the", "enzymes such as the respiratory", "such as the respiratory complexes", "the respiratory complexes aconitase", "complexes aconitase and", "aconitase and lipoate synthase", "and lipoate synthase through dedicated", "lipoate synthase through dedicated targeting", "synthase through dedicated targeting factors", "through dedicated targeting factors such", "dedicated targeting factors such as", "targeting factors such as ind1", "such as ind1 nfu1", "ind1 nfu1 and" ] }, { "record_id": "GLY_000594_1_1249", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "140180", "r hsa", "hsa 140180", "r hsa 140180" ] }, { "record_id": "GLY_000594_1_1249", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cox reactions", "arachidonic acid", "is a", "a 20", "20 carbon", "carbon unsaturated", "unsaturated fatty", "fatty acid", "acid which", "which is", "is present", "present in", "in the", "the lipid", "lipid bilayer", "bilayer of", "of all", "all mammalian", "mammalian cells.", "aa is", "is released", "released from", "from the", "the membrane", "membrane by", "by phospholipases", "thus making", "making it", "it available", "available for", "for conversion", "conversion to", "to bioactive", "bioactive lipids.", "lipids. the", "the cyclooxygenase", "cyclooxygenase pathway", "pathway is", "is one", "one of", "of three", "three pathways", "the others", "others being", "being lipoxygenase", "lipoxygenase and", "and p450", "p450 monooxygenase", "monooxygenase pathways", "that perform", "perform this", "this conversion.\\n\\nthe", "conversion.\\n\\nthe enzyme", "enzyme that", "that acts", "acts in", "is called", "called cyclooxygenase", "or prostaglandin", "prostaglandin h", "h synthase", "pghs .", ". pghs", "pghs exhibits", "exhibits a", "a dual", "dual catalytic", "catalytic activity", "a cyclooxygenase", "cyclooxygenase and", "and a", "a peroxidase.", "peroxidase. the", "cyclooxygenase catalyzes", "catalyzes the", "the initial", "initial conversion", "conversion of", "of aa", "aa to", "to an", "an intermediate", "prostaglandin g2", "whilst the", "the peroxidase", "peroxidase converts", "converts pgg2", "pgg2 to", "to prostaglandin", "prostaglandin h2", "via a", "a two", "two electron", "electron reduction.", "reduction. pgh2", "pgh2 is", "is the", "the intermediate", "intermediate for", "for products", "products that", "that play", "play critical", "critical roles", "roles in", "in immune", "immune function", "function regulation", "kidney development", "development and", "and mucosal", "mucosal integrity", "integrity of", "of the", "the gi", "gi tract.\\n\\npghs", "tract.\\n\\npghs exists", "exists in", "in two", "two isoforms", "1 and", "and 2", "2 and", "and both", "both forms", "forms can", "can perform", "perform the", "the above", "above reactions.", "reactions. form", "form 1", "1 is", "is constitutively", "constitutively expressed", "expressed in", "in most", "most tissues", "tissues and", "and is", "is involved", "involved in", "in performing", "performing normal", "normal physiological", "physiological functions.", "functions. form", "form 2", "in contrast", "is inducible", "inducible and", "in critical", "critical steps", "steps of", "of rheumatic", "rheumatic disease", "inflammation and", "and tumorigenesis.", "acid aa", "is a 20", "a 20 carbon", "20 carbon unsaturated", "carbon 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development", "regulation kidney development and", "kidney development and mucosal integrity", "development and mucosal integrity of", "and mucosal integrity of the", "mucosal integrity of the gi", "integrity of the gi tract.\\n\\npghs", "of the gi tract.\\n\\npghs exists", "the gi tract.\\n\\npghs exists in", "gi tract.\\n\\npghs exists in two", "tract.\\n\\npghs exists in two isoforms", "in two isoforms 1", "two isoforms 1 and", "isoforms 1 and 2", "1 and 2 and both", "and 2 and both forms", "2 and both forms can", "and both forms can perform", "both forms can perform the", "forms can perform the above", "can perform the above reactions.", "perform the above reactions. form", "the above reactions. form 1", "above reactions. form 1 is", "reactions. form 1 is constitutively", "form 1 is constitutively expressed", "1 is constitutively expressed in", "is constitutively expressed in most", "constitutively expressed in most tissues", "expressed in most tissues and", "in most tissues and 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"GLY_000594_1_1250", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biogenic amines", "amines are", "are oxidatively", "oxidatively deaminated", "deaminated to", "to aldehydes", "aldehydes by", "by maoa", "maoa and", "and maob", "biogenic amines are", "amines are oxidatively", "are oxidatively deaminated", "oxidatively deaminated to", "deaminated to aldehydes", "to aldehydes by", "aldehydes by maoa", "by maoa and", "maoa and maob", "biogenic amines are oxidatively", "amines are oxidatively deaminated", "are oxidatively deaminated to", "oxidatively deaminated to aldehydes", "deaminated to aldehydes by", "to aldehydes by maoa", "aldehydes by maoa and", "by maoa and maob", "biogenic amines are oxidatively deaminated", "amines are oxidatively deaminated to", "are oxidatively deaminated to aldehydes", "oxidatively deaminated to aldehydes by", "deaminated to aldehydes by maoa", "to aldehydes by maoa and", "aldehydes by maoa and maob", "human monoamine", 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specificities.", "specificities. mao", "primary type", "type in", "in fibroblasts", "preferentially oxidises", "oxidises serotonin", "5 hydroxytryptamine", "whereas mao", "mao b", "in platelets", "prefers phenylethylamine.", "phenylethylamine. maos", "maos are", "are of", "of particular", "particular clinical", "clinical interest", "interest because", "because of", "of the", "the use", "use of", "of mao", "mao inhibitors", "as antidepressants", "antidepressants or", "or in", "in the", "the treatment", "treatment of", "of neurodegenerative", "neurodegenerative diseases", "diseases benedetti", "benedetti 2001", "beedham 1997", "1997 .", "human monoamine oxidases", "oxidases maos", "are flavin containing", "flavin containing enzymes", "containing enzymes that", "enzymes that are", "that are present", "are present on", "present on the", "on the outer", "the outer mitochondrial", "outer mitochondrial membrane", "mitochondrial membrane and", "membrane and act", "and act on", "act on 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containing enzymes that", "containing enzymes that are", "enzymes that are present", "that are present on", "are present on the", "present on the outer", "on the outer mitochondrial", "the outer mitochondrial membrane", "outer mitochondrial membrane and", "mitochondrial membrane and act", "membrane and act on", "and act on primary", "on primary secondary", "primary secondary and", "secondary and tertiary amines.", "and tertiary amines. in", "tertiary amines. in contrast", "amines. in contrast to", "in contrast to the", "contrast to the p450s", "to the p450s which", "the p450s which have", "p450s which have a", "which have a large", "have a large number", "a large number of", "large number of isozymes", "of isozymes maos", "isozymes maos number", "maos number only two", "number only two isozymes", "two isozymes mao", "isozymes mao a", "mao a and mao", "a and mao b.", "and mao b. these", "mao b. these gene", "b. these gene products", "these gene products share", "gene products share over", "products share over 70%", "share over 70% sequence", "over 70% sequence identity", "sequence identity are", "identity are approximately", "are approximately 59kda in", "approximately 59kda in size", "59kda in size and", "in size and have", "size and have overlapping", "and have overlapping substrates", "overlapping substrates for", "substrates for example", "example dopamine tryamine", "dopamine tryamine and", "and tryptamine but", "tryptamine but each", "but each form also", "each form also has", "form also has distinct", "also has distinct substrate", "has distinct substrate specificities.", "distinct substrate specificities. mao", "substrate specificities. mao a", "mao a primary", "a primary type", "primary type in fibroblasts", "in fibroblasts preferentially", "fibroblasts preferentially oxidises", "oxidises serotonin 5", "serotonin 5 hydroxytryptamine", "5 hydroxytryptamine whereas", "hydroxytryptamine whereas mao", "mao b primary", "b primary type", "primary type in platelets", "in platelets prefers", "platelets prefers phenylethylamine.", "prefers phenylethylamine. maos are", "phenylethylamine. maos are of", "maos are of particular", "are of particular clinical", "of particular clinical interest", "particular clinical interest because", "clinical interest because of", "interest because of the", "because of the use", "of the use of", "the use of mao", "use of mao inhibitors", "mao inhibitors maoi", "maoi as antidepressants", "as antidepressants or in", "antidepressants or in the", "or in the treatment", "in the treatment of", "the treatment of neurodegenerative", "treatment of neurodegenerative diseases", "of neurodegenerative diseases benedetti", "neurodegenerative diseases benedetti 2001", "benedetti 2001 beedham", "2001 beedham 1997", "human monoamine oxidases maos", "oxidases maos are", "maos are flavin containing", "are flavin containing enzymes that", "flavin containing enzymes that are", "containing enzymes that are present", "enzymes that are present on", "that are present on the", "are present on the outer", "present on the outer mitochondrial", "on the outer mitochondrial membrane", "the outer mitochondrial membrane and", "outer mitochondrial membrane and act", "mitochondrial membrane and act on", "membrane and act on primary", "act on primary secondary", "on primary secondary and", "primary secondary and tertiary", "secondary and tertiary amines. in", "and tertiary amines. in contrast", "tertiary amines. in contrast to", "amines. in contrast to the", "in contrast to the p450s", "contrast to the p450s which", "to the p450s which have", "the p450s which have a", "p450s which have a large", "which have a large number", "have a large number of", "a large number of isozymes", "number of isozymes maos", "of isozymes maos number", "isozymes maos number only", "maos number only two isozymes", "only two isozymes mao", "two isozymes mao a", "isozymes mao a and", "mao a and mao b.", "a and mao b. these", "and mao b. these gene", "mao b. these gene products", "b. these gene products share", "these gene products share over", "gene products share over 70%", "products share over 70% sequence", "share over 70% sequence identity", "70% sequence identity are", "sequence identity are approximately", "identity are approximately 59kda", "are approximately 59kda in size", "approximately 59kda in size and", "59kda in size and have", "in size and have overlapping", "size and have overlapping substrates", "have overlapping substrates for", "overlapping substrates for example", "substrates for example dopamine", "for example dopamine tryamine", "example dopamine tryamine and", "dopamine tryamine and tryptamine", "tryamine and tryptamine but", "and tryptamine but each", "tryptamine but each form", "but each form also has", "each form also has distinct", "form also has distinct substrate", "also has distinct substrate specificities.", "has distinct substrate specificities. mao", "distinct substrate specificities. mao a", "specificities. mao a primary", "mao a primary type", "a primary type in", "type in fibroblasts preferentially", "in fibroblasts preferentially oxidises", "fibroblasts preferentially oxidises serotonin", "preferentially oxidises serotonin 5", "oxidises serotonin 5 hydroxytryptamine", "5 hydroxytryptamine whereas mao", "hydroxytryptamine whereas mao b", "whereas mao b primary", "mao b primary type", "b primary type in", "type in platelets prefers", "in platelets prefers phenylethylamine.", "platelets prefers phenylethylamine. maos", "prefers phenylethylamine. maos are of", "phenylethylamine. maos are of particular", "maos are of particular clinical", "are of particular clinical interest", "of particular clinical interest because", "particular clinical interest because of", "clinical interest because of the", "interest because of the use", "because of the use of", "of the use of mao", "the use of mao inhibitors", "of mao inhibitors maoi", "inhibitors maoi as", "maoi as antidepressants or", "as antidepressants or in the", "antidepressants or in the treatment", "or in the treatment of", "in the treatment of neurodegenerative", "the treatment of neurodegenerative diseases", "treatment of neurodegenerative diseases benedetti", "of neurodegenerative diseases benedetti 2001", "diseases benedetti 2001 beedham", "benedetti 2001 beedham 1997", "2001 beedham 1997 ." ] }, { "record_id": "GLY_000594_1_1251", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483115", "r hsa", "hsa 1483115", "r hsa 1483115" ] }, { "record_id": "GLY_000594_1_1251", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hydrolysis of", "of lpc", "hydrolysis of lpc", "is hydrolyzed", "hydrolyzed by", "by phospholipases", "phospholipases to", "to produce", "produce glycerophosphocholine", "which is", "is in", "in turn", "turn hydrolyzed", "by glycerophosphocholine", "glycerophosphocholine phosphodiesterase", "phosphodiesterase to", "produce choline", "and glycerol", "glycerol 3", "3 phosphate", "yamashita et", "et al.", "al. 2009", "al. 2005", "ghomashchi et", "al. 2010", "2010 .", "lysophosphatidylcholine lpc", "lpc is", "is hydrolyzed by", "hydrolyzed by phospholipases", "by phospholipases to", "phospholipases to produce", "to produce glycerophosphocholine", "glycerophosphocholine gpcho", "gpcho which", "which is in", "is in turn", "in turn hydrolyzed", "turn hydrolyzed by", "hydrolyzed by glycerophosphocholine", "by glycerophosphocholine phosphodiesterase", "glycerophosphocholine phosphodiesterase to", "phosphodiesterase to produce", "to produce choline", "choline cho", "cho and", "and glycerol 3", "glycerol 3 phosphate", "phosphate g3p", "yamashita et al.", "et al. 2009", "2009 yamashita", "et al. 2005", "2005 ghomashchi", "ghomashchi et al.", "et al. 2010", "al. 2010 .", "lpc is hydrolyzed", "is hydrolyzed by phospholipases", "hydrolyzed by phospholipases to", "by phospholipases to produce", "phospholipases to produce glycerophosphocholine", "produce glycerophosphocholine gpcho", "gpcho which is", "which is in turn", "is in turn hydrolyzed", "in turn hydrolyzed by", "turn hydrolyzed by glycerophosphocholine", "hydrolyzed by glycerophosphocholine phosphodiesterase", "by glycerophosphocholine phosphodiesterase to", "glycerophosphocholine phosphodiesterase to produce", "phosphodiesterase to produce choline", "produce choline cho", "cho and glycerol", "and glycerol 3 phosphate", "3 phosphate g3p", "g3p yamashita", "yamashita et al. 2009", "al. 2009 yamashita", "2009 yamashita et", "yamashita et al. 2005", "al. 2005 ghomashchi", "2005 ghomashchi et", "ghomashchi et al. 2010", "et al. 2010 .", "lysophosphatidylcholine lpc is", "lpc is hydrolyzed by", "is hydrolyzed by phospholipases to", "hydrolyzed by phospholipases to produce", "by phospholipases to produce glycerophosphocholine", "to produce glycerophosphocholine gpcho", "glycerophosphocholine gpcho which", "gpcho which is in", "which is in turn hydrolyzed", "is in turn hydrolyzed by", "in turn hydrolyzed by glycerophosphocholine", "turn hydrolyzed by glycerophosphocholine phosphodiesterase", "hydrolyzed by glycerophosphocholine phosphodiesterase to", "by glycerophosphocholine phosphodiesterase to produce", "glycerophosphocholine phosphodiesterase to produce choline", "to produce choline cho", "choline cho and", "cho and glycerol 3", "glycerol 3 phosphate g3p", "g3p yamashita et", "et al. 2009 yamashita", "al. 2009 yamashita et", "2009 yamashita et al.", "et al. 2005 ghomashchi", "al. 2005 ghomashchi et", "2005 ghomashchi et al.", "ghomashchi et al. 2010 ." ] }, { "record_id": "GLY_000594_1_1252", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1483191", "r hsa", "hsa 1483191", "r hsa 1483191" ] }, { "record_id": "GLY_000594_1_1252", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of pc", "synthesis of pc", "de novo", "kennedy pathway", "of phosphatidylcholine", "involves phosphorylation", "phosphorylation of", "of choline", "to phosphocholine", "followed by", "by condensing", "condensing with", "with cytidine", "cytidine triphosphate", "to form", "form cdp", "cdp choline", "cdp cho", "cho .", "and cdp", "cdp eta", "eta together", "together then", "then form", "form pc.", "pc is", "is formed", "formed when", "when phosphatidylethanolamine", "is methylated", "methylated by", "by phosphatidylethanolamine", "phosphatidylethanolamine n", "n methyltransferase", "henneberry et", "et al.", "al. 2002", "wright &", "& mcmaster", "mcmaster 2002", "2002 .", "novo               kennedy", "pathway synthesis", "synthesis of phosphatidylcholine", "phosphatidylcholine pc", "pc involves", "involves phosphorylation of", "phosphorylation of choline", "choline cho", "cho to", "phosphocholine pcho", "pcho followed", "followed by condensing", "by condensing with", "condensing with cytidine", "with cytidine triphosphate", "triphosphate ctp", "ctp to", "to form cdp", "form cdp choline", "choline cdp", "cdp cho .", ". diacylglycerol", "diacylglycerol dag", "dag and", "and cdp eta", "cdp eta together", "eta together then", "together then form", "then form pc.", "pc. alternatively", "alternatively pc", "pc is formed", "is formed when", "formed when phosphatidylethanolamine", "phosphatidylethanolamine pe", "pe is", "is methylated by", "methylated by phosphatidylethanolamine", "by phosphatidylethanolamine n", "phosphatidylethanolamine n methyltransferase", "methyltransferase pemt", "henneberry et al.", "et al. 2002", "2002 wright", "wright & mcmaster", "& mcmaster 2002", "mcmaster 2002 .", "de novo kennedy", "novo               kennedy pathway", "kennedy pathway synthesis", "pathway synthesis of", "of phosphatidylcholine pc", "pc involves phosphorylation", "involves phosphorylation of choline", "of choline cho", "cho to phosphocholine", "to phosphocholine pcho", "pcho followed by", "followed by condensing with", "by condensing with cytidine", "condensing with cytidine triphosphate", "cytidine triphosphate ctp", "ctp to form", "to form cdp choline", "cdp choline cdp", "choline cdp cho", "cho . diacylglycerol", "dag and cdp", "and cdp eta together", "cdp eta together then", "eta together then form", "together then form pc.", "form pc. alternatively", "alternatively pc is", "pc is formed when", "is formed when phosphatidylethanolamine", "when phosphatidylethanolamine pe", "pe is methylated", "is methylated by phosphatidylethanolamine", "methylated by phosphatidylethanolamine n", "by phosphatidylethanolamine n methyltransferase", "n methyltransferase pemt", "pemt henneberry", "henneberry et al. 2002", "al. 2002 wright", "2002 wright &", "wright & mcmaster 2002", "& mcmaster 2002 .", "de novo kennedy pathway", "kennedy pathway synthesis of", "pathway synthesis of phosphatidylcholine", "synthesis of phosphatidylcholine pc", "phosphatidylcholine pc involves", "pc involves phosphorylation of", "phosphorylation of choline cho", "choline cho to", "phosphocholine pcho followed", "pcho followed by condensing", "followed by condensing with cytidine", "by condensing with cytidine triphosphate", "with cytidine triphosphate ctp", "triphosphate ctp to", "ctp to form cdp", "form cdp choline cdp", "cdp choline cdp cho", "choline cdp cho .", "cdp cho . diacylglycerol", ". diacylglycerol dag", "diacylglycerol dag and", "dag and cdp eta", "and cdp eta together then", "cdp eta together then form", "eta together then form pc.", "then form pc. alternatively", "pc. alternatively pc", "alternatively pc is formed", "pc is formed when phosphatidylethanolamine", "formed when phosphatidylethanolamine pe", "phosphatidylethanolamine pe is", "pe is methylated by", "is methylated by phosphatidylethanolamine n", "methylated by phosphatidylethanolamine n methyltransferase", "phosphatidylethanolamine n methyltransferase pemt", "pemt henneberry et", "et al. 2002 wright", "al. 2002 wright &", "2002 wright & mcmaster", "wright & mcmaster 2002 ." ] }, { "record_id": "GLY_000594_1_1253", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "156581", "r hsa", "hsa 156581", "r hsa 156581" ] }, { "record_id": "GLY_000594_1_1253", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "methylation is", "is a", "a common", "common but", "but minor", "minor pathway", "pathway of", "of phase", "phase ii", "ii conjugation", "conjugation compared", "compared to", "to glucuronidation", "glucuronidation or", "or sulfonation.", "the cofactor", "cofactor used", "used in", "in methylation", "methylation conjugation", "conjugation is", "is s", "s adenosylmethionine", "sam .", "sam is", "is the", "the second", "second most", "most widely", "widely used", "used enzyme", "enzyme substrate", "substrate after", "after atp", "atp and", "and is", "is involved", "involved in", "in a", "a wide", "wide range", "range of", "of important", "important biological", "biological processes.", "processes. sam", "is sythesized", "sythesized from", "from methionine's", "methionine's reaction", "reaction with", "with atp", "catalyzed by", "by methionine", "methionine adenosyltransferase", "mat .", "there are", "are two", "two genes", "mat1a and", "and mat2a", "which encode", "encode for", "for two", "two homologous", "homologous mat", "mat catalytic", "catalytic subunits", "1 and", "and 2.
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              fuctional", "the cycle.
              fuctional groups", "cycle.
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              during conjugation", "and 2.
              during conjugation with", "2.
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              fuctional", "completing the cycle.
              fuctional groups", "the cycle.
              fuctional groups attacked", "cycle.
              fuctional groups attacked are", "groups attacked are phenols", "are phenols catechols", "catechols aliphatic and", "aliphatic and aromatic amines", "and aromatic amines and", "aromatic amines and sulfhydryl", "amines and sulfhydryl containing", "and sulfhydryl containing groups.", "sulfhydryl containing groups. the", "containing groups. the enzymes", "groups. the enzymes that", "the enzymes that catalyze", "enzymes that catalyze the", "that catalyze the transfer", "catalyze the transfer of", "the transfer of the", "transfer of the methyl", "of the methyl group", "the methyl group to", "methyl group to these", "group to these functional", "to these functional groups", "these functional groups are", "functional groups are the", "groups are the methyltransferases", "the methyltransferases mt", "methyltransferases mt .", "mt . mts are", ". mts are small", "are small cytosolic", "cytosolic monomeric enzymes", "monomeric enzymes that utilize", "enzymes that utilize sam", "that utilize sam as", "utilize sam as a", "sam as a methyl", "as a methyl donor.", "a methyl donor. there", "methyl donor. there are", "donor. there are many", "there are many mts", "are many mts but", "many mts but the", "mts but the best", "but the best studied", "the best studied ones", "best studied ones are", "studied ones are named", "ones are named on", "are named on the", "named on the basis", "on the basis of", "the basis of their", "basis of their prototypical", "of their prototypical substrates:", "their prototypical substrates: comt", "substrates: comt catechol", "comt catechol o", "catechol o methyltransferase ", "methyltransferase tpmt", "tpmt thiopurine methyltransferase", "methyltransferase tmt", "tmt thiol methyltransferase", "methyltransferase hnmt", "hnmt histamine n", "histamine n methyltransferase ", "n methyltransferase and", "methyltransferase and nnmt", "and nnmt nicotinamide", "nnmt nicotinamide n", "nicotinamide n methyltransferase .", "n methyltransferase . an", "methyltransferase . an example", ". an example of", "an example of each", "example of each enzyme", "of each enzyme mentioned", "each enzyme mentioned is", "enzyme mentioned is given.", "mentioned is given. in", "is given. in each", "given. in each case", "each case a", "case a typical", "a typical substrate for", "typical substrate for the", "substrate for the enzyme", "for the enzyme is", "the enzyme is shown.", "methylation is a common but", "is a common but minor", "a common but minor pathway", "common but minor pathway of", "but minor pathway of phase", "minor pathway of phase ii", "pathway of phase ii conjugation", "of phase ii conjugation compared", "phase ii conjugation compared to", "ii conjugation compared to glucuronidation", "conjugation compared to glucuronidation or", "compared to glucuronidation or sulfonation.", "glucuronidation or sulfonation. the", "or sulfonation. the cofactor", "sulfonation. the cofactor used", "the cofactor used in methylation", "cofactor used in methylation conjugation", "used in methylation conjugation is", "in methylation conjugation is s", "methylation conjugation is s adenosylmethionine", "is s adenosylmethionine sam", "s adenosylmethionine sam .", "sam . sam is", ". sam is the", "sam is the second most", "is the second most widely", "the second most widely used", "second most widely used enzyme", "most widely used enzyme substrate", "widely used enzyme substrate after", "used enzyme substrate after atp", "enzyme substrate after atp and", "substrate after atp and is", "after atp and is involved", "atp and is involved in", "and is involved in a", "is involved in a wide", "involved in a wide range", "in a wide range of", "a wide range of important", "wide range of important biological", "range of important biological processes.", "of important biological processes. sam", "important biological processes. sam is", "biological processes. sam is sythesized", "processes. sam is sythesized from", "sam is sythesized from methionine's", "is sythesized from methionine's reaction", "sythesized from methionine's reaction with", "from methionine's reaction with atp", "reaction with atp catalyzed", "with atp catalyzed by", "atp catalyzed by methionine", "by methionine adenosyltransferase mat", "methionine adenosyltransferase mat .", "mat . there are", ". there are two", "are two genes mat1a", "two genes mat1a and", "genes mat1a and mat2a", "mat1a and mat2a which", "and mat2a which encode", "mat2a which encode for", "which encode for two homologous", "encode for two homologous mat", "for two homologous mat catalytic", "two homologous mat catalytic subunits", "mat catalytic subunits 1", "catalytic subunits 1 and", "subunits 1 and 2.
              during", "1 and 2.
              during conjugation with", "and 2.
              during conjugation with nucleophilic", "2.
              during conjugation with nucleophilic substrates", "with nucleophilic substrates the", "nucleophilic substrates the methyl", "substrates the methyl group", "the methyl group attached to", "methyl group attached to the", "group attached to the sulfonium", "attached to the sulfonium ion", "to the sulfonium ion of", "the sulfonium ion of sam", "sulfonium ion of sam is", "ion of sam is transferred", "of sam is transferred to", "sam is transferred to the", "is transferred to the substrate", "transferred to the substrate forming", "to the substrate forming the", "the substrate forming the conjugate.", "substrate forming the conjugate. sam", "the conjugate. sam having", "conjugate. sam having lost", "sam having lost the", "having lost the methyl moiety", "the methyl moiety is", "methyl moiety is converted", "moiety is converted to", "is converted to s adenosylhomocysteine", "to s adenosylhomocysteine sah", "s adenosylhomocysteine sah .", "sah . sah can", ". sah can be", "sah can be hydrolyzed to", "can be hydrolyzed to form", "be hydrolyzed to form adenosine", "hydrolyzed to form adenosine and", "to form adenosine and homocysteine.", "form adenosine and homocysteine. homocysteine", "adenosine and homocysteine. homocysteine can", "and homocysteine. homocysteine can either", "homocysteine. homocysteine can either be", "homocysteine can either be converted", "can either be converted to", "either be converted to glutathione", "be converted to glutathione or", "converted to glutathione or methylated", "to glutathione or methylated to", "glutathione or methylated to form", "or methylated to form methionine", "to form methionine thus", "form methionine thus forming", "methionine thus forming the", "thus forming the starting point", "forming the starting point for", "the starting point for sam", "starting point for sam synthesis", "point for sam synthesis and", "for sam synthesis and completing", "sam synthesis and completing the", "synthesis and completing the cycle.
              fuctional", "and completing the cycle.
              fuctional groups", "completing the cycle.
              fuctional groups attacked", "the cycle.
              fuctional groups attacked are", "cycle.
              fuctional groups attacked are phenols", "attacked are phenols catechols", "phenols catechols aliphatic", "catechols aliphatic and aromatic", "aliphatic and aromatic amines and", "and aromatic amines and sulfhydryl", "aromatic amines and sulfhydryl containing", "amines and sulfhydryl containing groups.", "and sulfhydryl containing groups. the", "sulfhydryl containing groups. the enzymes", "containing groups. the enzymes that", "groups. the enzymes that catalyze", "the enzymes that catalyze the", "enzymes that catalyze the transfer", "that catalyze the transfer of", "catalyze the transfer of the", "the transfer of the methyl", "transfer of the methyl group", "of the methyl group to", "the methyl group to these", "methyl group to these functional", "group to these functional groups", "to these functional groups are", "these functional groups are the", "functional groups are the methyltransferases", "are the methyltransferases mt", "the methyltransferases mt .", "methyltransferases mt . mts", "mt . mts are small", "mts are small cytosolic", "small cytosolic monomeric", "cytosolic monomeric enzymes that", "monomeric enzymes that utilize sam", "enzymes that utilize sam as", "that utilize sam as a", "utilize sam as a methyl", "sam as a methyl donor.", "as a methyl donor. there", "a methyl donor. there are", "methyl donor. there are many", "donor. there are many mts", "there are many mts but", "are many mts but the", "many mts but the best", "mts but the best studied", "but the best studied ones", "the best studied ones are", "best studied ones are named", "studied ones are named on", "ones are named on the", "are named on the basis", "named on the basis of", "on the basis of their", "the basis of their prototypical", "basis of their prototypical substrates:", "of their prototypical substrates: comt", "prototypical substrates: comt catechol", "substrates: comt catechol o", "comt catechol o methyltransferase", "o methyltransferase tpmt", " tpmt thiopurine", "tpmt thiopurine methyltransferase ", "thiopurine methyltransferase tmt", " tmt thiol", "tmt thiol methyltransferase ", "thiol methyltransferase hnmt", " hnmt histamine", "hnmt histamine n methyltransferase", "histamine n methyltransferase and", "n methyltransferase and nnmt", " and nnmt nicotinamide", "and nnmt nicotinamide n", "nnmt nicotinamide n methyltransferase", "nicotinamide n methyltransferase . an", "n methyltransferase . an example", "methyltransferase . an example of", ". an example of each", "an example of each enzyme", "example of each enzyme mentioned", "of each enzyme mentioned is", "each enzyme mentioned is given.", "enzyme mentioned is given. in", "mentioned is given. in each", "is given. in each case", "in each case a", "each case a typical", "case a typical substrate", "a typical substrate for the", "typical substrate for the enzyme", "substrate for the enzyme is", "for the enzyme is shown." ] }, { "record_id": "GLY_000594_1_1254", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "156582", "r hsa", "hsa 156582", "r hsa 156582" ] }, { "record_id": "GLY_000594_1_1254", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "n acetyltransferases", "ec 2.3.1.5", "utilize acetyl", "acetyl co", "co a", "a in", "in acetylation", "acetylation conjugation", "conjugation reactions.", "reactions. this", "this is", "is the", "the preferred", "preferred route", "route of", "of conjugating", "conjugating aromatic", "aromatic amines", "r nh2", "converted to", "to aromatic", "aromatic amides", "amides r", "r nh", "nh coch3", "and hydrazines", "nh nh2", "to r", "nh nh", "coch3 .", ". aliphatic", "aliphatic amines", "amines are", "are not", "not substrates", "substrates for", "for nat.", "nat. the", "the basic", "basic reaction", "reaction is

              acetyl", "is

              acetyl coa", "coa +", "+ an", "an arylamine", "arylamine =", "= coa", "an n", "acetylarylamine


              nats are", "are cytosolic", "cytosolic and", "and in", "in humans", "2 isoforms", "isoforms are", "are expressed", "nat1 and", "and nat2.", "nat2. a", "a third", "third isoform", "is a", "a pseudogene", "pseudogene and", "and is", "is not", "not expressed.", "expressed. the", "the nat2", "nat2 gene", "gene contains", "contains mutations", "mutations that", "that decrease", "decrease nat2", "nat2 activity.", "activity. this", "this mutations", "mutations was", "was first", "first seen", "seen as", "as slow", "slow acetylation", "compared to", "to the", "the normal", "fast acetylation", "acetylation of", "of the", "the antituberculosis", "antituberculosis drug", "drug isoniazid.", "incidence of", "the slow", "slow acetylator", "acetylator phenotype", "phenotype is", "is high", "high in", "in middle", "middle eastern", "eastern populations", "in europeans", "americans and", "and australians", "australians and", "and low", "low in", "in asians", "<25% in", "in chinese", "japanese and", "and koreans", "koreans .", ". n", "n acetylation", "acetylation and", "and methylation", "methylation pathways", "pathways differ", "differ from", "from other", "other conjugation", "conjugation pathways", "pathways in", "in that", "that they", "they mask", "mask an", "an amine", "amine with", "with a", "a nonionizable", "nonionizable group", "group so", "so that", "that the", "the conjugates", "conjugates are", "are less", "less water", "water soluble", "soluble than", "than the", "the parent", "parent compound.", "compound. however", "certain n", "n acetlylations", "acetlylations facilitate", "facilitate urinary", "urinary excretion.
              n", "excretion.
              n acetylation", "acetylation occurs", "occurs in", "in two", "two sequential", "sequential steps", "steps via", "via a", "a ping", "ping pong", "pong bi", "bi bi", "bi mechanism.", "mechanism. in", "in the", "the first", "first step", "the acetyl", "acetyl group", "group from", "from acetyl", "acetyl coa", "coa is", "is transferred", "transferred to", "to a", "a cysteine", "cysteine residue", "residue in", "in nat", "with consequent", "consequent release", "release of", "of coenzyme", "coenzyme a.", "a. in", "the second", "second step", "group is", "is released", "released from", "from the", "the acetylated", "acetylated nat", "nat to", "the substrate", "subsequently regenerating", "regenerating the", "the enzyme.", "acetyltransferases nats", "nats ec", "2.3.1.5 utilize", "utilize acetyl co", "acetyl co a", "co a in", "a in acetylation", "in acetylation conjugation", "acetylation conjugation reactions.", "conjugation reactions. this", "reactions. this is", "this is the", "is the preferred", "the preferred route", "preferred route of", "route of conjugating", "of conjugating aromatic", "conjugating aromatic amines", "amines r", "nh2 converted", "converted to aromatic", "to aromatic amides", "aromatic amides r", "amides r nh", "r nh coch3", "coch3 and", "hydrazines r", "r nh nh2", "converted to r", "to r nh", "r nh nh", "nh nh coch3", "nh coch3 .", "coch3 . aliphatic", ". aliphatic amines", "aliphatic amines are", "amines are not", "are not substrates", "not substrates for", "substrates for nat.", "for nat. the", "nat. the basic", "the basic reaction", "basic reaction is

              acetyl", "reaction is

              acetyl coa", "is

              acetyl coa +", "coa + an", "+ an arylamine", "an arylamine =", "arylamine = coa", "= coa +", "+ an n", "n acetylarylamine


              nats", "acetylarylamine


              nats are cytosolic", "are cytosolic and", "cytosolic and in", "and in humans", "humans 2", "2 isoforms are", "isoforms are expressed", "expressed nat1", "nat1 and nat2.", "and nat2. a", "nat2. a third", "a third isoform", "isoform natp", "natp is", "is a pseudogene", "a pseudogene and", "pseudogene and is", "and is not", "is not expressed.", "not expressed. the", "expressed. the nat2", "the nat2 gene", "nat2 gene contains", "gene contains mutations", "contains mutations that", "mutations that decrease", "that decrease nat2", "decrease nat2 activity.", "nat2 activity. this", "activity. this mutations", "this mutations was", "mutations was first", "was first seen", "first seen as", "seen as slow", "as slow acetylation", "acetylation compared", "compared to the", "to the normal", "normal fast", "fast acetylation of", "acetylation of the", "of the antituberculosis", "the antituberculosis drug", "antituberculosis drug isoniazid.", "isoniazid. incidence", "incidence of the", "of the slow", "the slow acetylator", "slow acetylator phenotype", "acetylator phenotype is", "phenotype is high", "is high in", "high in middle", "in middle eastern", "middle eastern populations", "populations 70%", "average 50%", "50% in", "europeans americans", "americans and australians", "and australians and", "australians and low", "and low in", "low in asians", "asians <25%", "<25% in chinese", "chinese japanese", "japanese and koreans", "and koreans .", "koreans . n", ". n acetylation", "n acetylation and", "acetylation and methylation", "and methylation pathways", "methylation pathways differ", "pathways differ from", "differ from other", "from other conjugation", "other conjugation pathways", "conjugation pathways in", "pathways in that", "in that they", "that they mask", "they mask an", "mask an amine", "an amine with", "amine with a", "with a nonionizable", "a nonionizable group", "nonionizable group so", "group so that", "so that the", "that the conjugates", "the conjugates are", "conjugates are less", "are less water", "less water soluble", "water soluble than", "soluble than the", "than the parent", "the parent compound.", "parent compound. however", "however certain", "certain n acetlylations", "n acetlylations facilitate", "acetlylations facilitate urinary", "facilitate urinary excretion.
              n", "urinary excretion.
              n acetylation", "excretion.
              n acetylation occurs", "acetylation occurs in", "occurs in two", "in two sequential", "two sequential steps", "sequential steps via", "steps via a", "via a ping", "a ping pong", "ping pong bi", "pong bi bi", "bi bi mechanism.", "bi mechanism. in", "mechanism. in the", "in the first", "the first step", "step the", "the acetyl group", "acetyl group from", "group from acetyl", "from acetyl coa", "acetyl coa is", "coa is transferred", "is transferred to", "transferred to a", "to a cysteine", "a cysteine residue", "cysteine residue in", "residue in nat", "nat with", "with consequent release", "consequent release of", "release of coenzyme", "of coenzyme a.", "coenzyme a. in", "a. in the", "in the second", "the second step", "acetyl group is", "group is released", "is released from", "released from the", "from the acetylated", "the acetylated nat", "acetylated nat to", "nat to the", "to the substrate", "substrate subsequently", "subsequently regenerating the", "regenerating the enzyme.", "n acetyltransferases nats", "nats ec 2.3.1.5", "ec 2.3.1.5 utilize", "2.3.1.5 utilize acetyl", "utilize acetyl co a", "acetyl co a in", "co a in acetylation", "a in acetylation conjugation", "in acetylation conjugation reactions.", "acetylation conjugation reactions. this", "conjugation reactions. this is", "reactions. this is the", "this is the preferred", "is the preferred route", "the preferred route of", "preferred route of conjugating", "route of conjugating aromatic", "of conjugating aromatic amines", "aromatic amines r", "amines r nh2", "r nh2 converted", "nh2 converted to", "converted to aromatic amides", "to aromatic amides r", "aromatic amides r nh", "amides r nh coch3", "nh coch3 and", "coch3 and hydrazines", "and hydrazines r", "hydrazines r nh", "nh nh2 converted", "converted to r nh", "to r nh nh", "r nh nh coch3", "nh nh coch3 .", "nh coch3 . aliphatic", "coch3 . aliphatic amines", ". aliphatic amines are", "aliphatic amines are not", "amines are not substrates", "are not substrates for", "not substrates for nat.", "substrates for nat. the", "for nat. the basic", "nat. the basic reaction", "the basic reaction is

              acetyl", "basic reaction is

              acetyl coa", "reaction is

              acetyl coa +", "is

              acetyl coa + an", "coa + an arylamine", "+ an arylamine =", "an arylamine = coa", "arylamine = coa +", "= coa + an", "coa + an n", "an n acetylarylamine


              nats", "n acetylarylamine


              nats are", "acetylarylamine


              nats are cytosolic and", "are cytosolic and in", "cytosolic and in humans", "in humans 2", "humans 2 isoforms", "2 isoforms are expressed", "are expressed nat1", "expressed nat1 and", "nat1 and nat2. a", "and nat2. a third", "nat2. a third isoform", "third isoform natp", "natp is a", "is a pseudogene and", "a pseudogene and is", "pseudogene and is not", "and is not expressed.", "is not expressed. the", "not expressed. the nat2", "expressed. the nat2 gene", "the nat2 gene contains", "nat2 gene contains mutations", "gene contains mutations that", "contains mutations that decrease", "mutations that decrease nat2", "that decrease nat2 activity.", "decrease nat2 activity. this", "nat2 activity. this mutations", "activity. this mutations was", "this mutations was first", "mutations was first seen", "was first seen as", "first seen as slow", "seen as slow acetylation", "slow acetylation compared", "acetylation compared to", "compared to the normal", "the normal fast", "normal fast acetylation", "fast acetylation of the", "acetylation of the antituberculosis", "of the antituberculosis drug", "the antituberculosis drug isoniazid.", "drug isoniazid. incidence", "isoniazid. incidence of", "incidence of the slow", "of the slow acetylator", "the slow acetylator phenotype", "slow acetylator phenotype is", "acetylator phenotype is high", "phenotype is high in", "is high in middle", "high in middle eastern", "in middle eastern populations", "eastern populations 70%", "70% average", "50% in europeans", "in europeans americans", "europeans americans and", "americans and australians and", "and australians and low", "australians and low in", "and low in asians", "in asians <25%", "asians <25% in", "in chinese japanese", "chinese japanese and", "japanese and koreans .", "and koreans . n", "koreans . n acetylation", ". n acetylation and", "n acetylation and methylation", "acetylation and methylation pathways", "and methylation pathways differ", "methylation pathways differ from", "pathways differ from other", "differ from other conjugation", "from other conjugation pathways", "other conjugation pathways in", "conjugation pathways in that", "pathways in that they", "in that they mask", "that they mask an", "they mask an amine", "mask an amine with", "an amine with a", "amine with a nonionizable", "with a nonionizable group", "a nonionizable group so", "nonionizable group so that", "group so that the", "so that the conjugates", "that the conjugates are", "the conjugates are less", "conjugates are less water", "are less water soluble", "less water soluble than", "water soluble than the", "soluble than the parent", "than the parent compound.", "the parent compound. however", "compound. however certain", "however certain n", "certain n acetlylations facilitate", "n acetlylations facilitate urinary", "acetlylations facilitate urinary excretion.
              n", "facilitate urinary excretion.
              n acetylation", "urinary excretion.
              n acetylation occurs", "excretion.
              n acetylation occurs in", "acetylation occurs in two", "occurs in two sequential", "in two sequential steps", "two sequential steps via", "sequential steps via a", "steps via a ping", "via a ping pong", "a ping pong bi", "ping pong bi bi", "pong bi bi mechanism.", "bi bi mechanism. in", "bi mechanism. in the", "mechanism. in the first", "in the first step", "first step the", "step the acetyl", "the acetyl group from", "acetyl group from acetyl", "group from acetyl coa", "from acetyl coa is", "acetyl coa is transferred", "coa is transferred to", "is transferred to a", "transferred to a cysteine", "to a cysteine residue", "a cysteine residue in", "cysteine residue in nat", "in nat with", "nat with consequent", "with consequent release of", "consequent release of coenzyme", "release of coenzyme a.", "of coenzyme a. in", "coenzyme a. in the", "a. in the second", "in the second step", "second step the", "the acetyl group is", "acetyl group is released", "group is released from", "is released from the", "released from the acetylated", "from the acetylated nat", "the acetylated nat to", "acetylated nat to the", "nat to the substrate", "the substrate subsequently", "substrate subsequently regenerating", "subsequently regenerating the enzyme.", "acetyltransferases nats ec", "ec 2.3.1.5 utilize acetyl", "2.3.1.5 utilize acetyl co", "utilize acetyl co a in", "acetyl co a in acetylation", "co a in acetylation conjugation", "a in acetylation conjugation reactions.", "in acetylation conjugation reactions. this", "acetylation conjugation reactions. this is", "conjugation reactions. this is the", "reactions. this is the preferred", "this is the preferred route", "is the preferred route of", "the preferred route of conjugating", "preferred route of conjugating aromatic", "route of conjugating aromatic amines", "conjugating aromatic amines r", "aromatic amines r nh2", "r nh2 converted to", "nh2 converted to aromatic", "converted to aromatic amides r", "to aromatic amides r nh", "aromatic amides r nh coch3", "r nh coch3 and", "nh coch3 and hydrazines", "and hydrazines r nh", "hydrazines r nh nh2", "r nh nh2 converted", "nh nh2 converted to", "nh2 converted to r", "converted to r nh nh", "to r nh nh coch3", "r nh nh coch3 .", "nh nh coch3 . aliphatic", "nh coch3 . aliphatic amines", "coch3 . aliphatic amines are", ". aliphatic amines are not", "aliphatic amines are not substrates", "amines are not substrates for", "are not substrates for nat.", "not substrates for nat. the", "substrates for nat. the basic", "for nat. the basic reaction", "nat. the basic reaction is

              acetyl", "the basic reaction is

              acetyl coa", "basic reaction is

              acetyl coa +", "reaction is

              acetyl coa + an", "is

              acetyl coa + an arylamine", "coa + an arylamine =", "+ an arylamine = coa", "an arylamine = coa +", "arylamine = coa + an", "= coa + an n", "+ an n acetylarylamine


              nats", "an n acetylarylamine


              nats are", "n acetylarylamine


              nats are cytosolic", "acetylarylamine


              nats are cytosolic and in", "are cytosolic and in humans", "and in humans 2", "in humans 2 isoforms", "humans 2 isoforms are", "isoforms are expressed nat1", "are expressed nat1 and", "expressed nat1 and nat2.", "nat1 and nat2. a third", "and nat2. a third isoform", "a third isoform natp", "isoform natp is", "natp is a pseudogene", "is a pseudogene and is", "a pseudogene and is not", "pseudogene and is not expressed.", "and is not expressed. the", "is not expressed. the nat2", "not expressed. the nat2 gene", "expressed. the nat2 gene contains", "the nat2 gene contains mutations", "nat2 gene contains mutations that", "gene contains mutations that decrease", "contains mutations that decrease nat2", "mutations that decrease nat2 activity.", "that decrease nat2 activity. this", "decrease nat2 activity. this mutations", "nat2 activity. this mutations was", "activity. this mutations was first", "this mutations was first seen", "mutations was first seen as", "was first seen as slow", "first seen as slow acetylation", "as slow acetylation compared", "slow acetylation compared to", "acetylation compared to the", "to the normal fast", "the normal fast acetylation", "normal fast acetylation of", "fast acetylation of the antituberculosis", "acetylation of the antituberculosis drug", "of the antituberculosis drug isoniazid.", "antituberculosis drug isoniazid. incidence", "drug isoniazid. incidence of", "isoniazid. incidence of the", "incidence of the slow acetylator", "of the slow acetylator phenotype", "the slow acetylator phenotype is", "slow acetylator phenotype is high", "acetylator phenotype is high in", "phenotype is high in middle", "is high in middle eastern", "high in middle eastern populations", "middle eastern populations 70%", "average 50% in", "in europeans americans and", "europeans americans and australians", "americans and australians and low", "and australians and low in", "australians and low in asians", "low in asians <25%", "in asians <25% in", "asians <25% in chinese", "<25% in chinese japanese", "in chinese japanese and", "chinese japanese and koreans", "japanese and koreans . n", "and koreans . n acetylation", "koreans . n acetylation and", ". n acetylation and methylation", "n acetylation and methylation pathways", "acetylation and methylation pathways differ", "and methylation pathways differ from", "methylation pathways differ from other", "pathways differ from other conjugation", "differ from other conjugation pathways", "from other conjugation pathways in", "other conjugation pathways in that", "conjugation pathways in that they", "pathways in that they mask", "in that they mask an", "that they mask an amine", "they mask an amine with", "mask an amine with a", "an amine with a nonionizable", "amine with a nonionizable group", "with a nonionizable group so", "a nonionizable group so that", "nonionizable group so that the", "group so that the conjugates", "so that the conjugates are", "that the conjugates are less", "the conjugates are less water", "conjugates are less water soluble", "are less water soluble than", "less water soluble than the", "water soluble than the parent", "soluble than the parent compound.", "than the parent compound. however", "parent compound. however certain", "compound. however certain n", "however certain n acetlylations", "certain n acetlylations facilitate urinary", "n acetlylations facilitate urinary excretion.
              n", "acetlylations facilitate urinary excretion.
              n acetylation", "facilitate urinary excretion.
              n acetylation occurs", "urinary excretion.
              n acetylation occurs in", "excretion.
              n acetylation occurs in two", "acetylation occurs in two sequential", "occurs in two sequential steps", "in two sequential steps via", "two sequential steps via a", "sequential steps via a ping", "steps via a ping pong", "via a ping pong bi", "a ping pong bi bi", "ping pong bi bi mechanism.", "pong bi bi mechanism. in", "bi bi mechanism. in the", "bi mechanism. in the first", "mechanism. in the first step", "the first step the", "first step the acetyl", "step the acetyl group", "the acetyl group from acetyl", "acetyl group from acetyl coa", "group from acetyl coa is", "from acetyl coa is transferred", "acetyl coa is transferred to", "coa is transferred to a", "is transferred to a cysteine", "transferred to a cysteine residue", "to a cysteine residue in", "a cysteine residue in nat", "residue in nat with", "in nat with consequent", "nat with consequent release", "with consequent release of coenzyme", "consequent release of coenzyme a.", "release of coenzyme a. in", "of coenzyme a. in the", "coenzyme a. in the second", "a. in the second step", "the second step the", "second step the acetyl", "the acetyl group is released", "acetyl group is released from", "group is released from the", "is released from the acetylated", "released from the acetylated nat", "from the acetylated nat to", "the acetylated nat to the", "acetylated nat to the substrate", "to the substrate subsequently", "the substrate subsequently regenerating", "substrate subsequently regenerating the" ] }, { "record_id": "GLY_000594_1_1255", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1566948", "r hsa", "hsa 1566948", "r hsa 1566948" ] }, { "record_id": "GLY_000594_1_1255", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "elastic fibre", "fibre formation", "elastic fibre formation", "elastic fibres", "are a", "a major", "major structural", "structural constituent", "constituent of", "of dynamic", "dynamic connective", "connective tissues", "tissues such", "such as", "as large", "large arteries", "arteries and", "and lung", "lung parenchyma", "where they", "they provide", "provide essential", "essential properties", "properties of", "of elastic", "elastic recoil", "recoil and", "and resilience.", "resilience. ef", "ef are", "are composed", "composed of", "of a", "a central", "central cross", "cross linked", "linked core", "core of", "of elastin", "surrounded by", "by a", "a mesh", "mesh of", "of microfibrils", "which are", "composed largely", "largely of", "of fibrillin.", "fibrillin. in", "in addition", "addition to", "to elastin", "elastin and", "and fibrillin", "fibrillin 1", "over 30", "30 ancillary", "ancillary proteins", "proteins are", "are involved", "involved in", "in mediating", "mediating important", "important roles", "roles in", "in elastic", "fibre assembly", "assembly as", "as well", "well as", "as interactions", "interactions with", "with the", "the surrounding", "surrounding environment.", "environment. these", "these include", "include fibulins", "elastin microfibril", "microfibril interface", "interface located", "located proteins", "microfibril associated", "associated glycoproteins", "and latent", "latent tgf", "tgf beta", "beta binding", "binding proteins", "ltbps .", ". fibulin", "fibulin 5", "5 for", "for example", "is expressed", "expressed by", "by vascular", "vascular smooth", "smooth muscle", "muscle cells", "cells and", "and plays", "plays an", "an essential", "essential role", "role in", "in the", "the formation", "formation of", "fibres through", "through mediating", "mediating interactions", "interactions between", "between elastin", "yanigasawa et", "et al.", "al. 2002", "freeman et", "al. 2005", "2005 .", ". in", "it plays", "plays a", "a role", "in cell", "cell adhesion", "adhesion through", "through integrin", "integrin receptors", "receptors and", "and has", "has been", "been shown", "shown to", "to influence", "influence smooth", "muscle cell", "cell proliferation", "nakamura et", "2002 .", ". emilins", "emilins are", "a family", "family of", "of homologous", "homologous glycoproteins", "glycoproteins originally", "originally identified", "identified in", "in extracts", "extracts of", "of aortas.", "aortas. found", "found at", "at the", "the elastin", "elastin fibrillin", "fibrillin interface", "early studies", "studies showed", "showed that", "that antibodies", "antibodies to", "to emilin", "emilin can", "can affect", "affect the", "the process", "process of", "bressan et", "al. 1993", "1993 .", ". emilin1", "emilin1 has", "to bind", "bind elastin", "and fibulin", "5 and", "and appears", "appears to", "to coordinate", "coordinate their", "their common", "common interaction", "zanetti et", "al. 2004", "2004 .", ". magps", "magps are", "are found", "found to", "to co", "co localize", "localize with", "with microfibrils.", "microfibrils. magp", "magp 1", "binds strongly", "strongly to", "to an", "an n", "n terminal", "terminal sequence", "sequence of", "of fibrillin", "fibrillin 1.", "1. other", "other proteins", "proteins found", "found associated", "associated with", "with microfibrils", "microfibrils include", "include vitronectin", "dahlback et", "al. 1990", "1990 .

              fibrillin", ".

              fibrillin is", "is most", "most familiar", "familiar as", "as a", "a component", "component of", "fibres but", "but microfibrils", "microfibrils with", "with no", "no elastin", "elastin are", "found in", "the ciliary", "ciliary zonules", "zonules of", "of the", "the eye", "eye and", "and invertebrate", "invertebrate circulatory", "circulatory systems.", "systems. the", "the addition", "addition of", "elastin to", "to microfibrils", "microfibrils is", "is a", "a vertebrate", "vertebrate adaptation", "adaptation to", "to high", "high pulsatile", "pulsatile pressures", "pressures in", "in their", "their closed", "closed circulatory", "circulatory systems", "faury et", "al. 2003", "2003 .", ". elastin", "elastin appears", "to have", "have emerged", "emerged after", "after the", "the divergence", "divergence of", "of jawless", "jawless vertebrates", "vertebrates from", "from other", "other vertebrates", "sage 1982", "1982 .", ".

              fibrillin", "

              fibrillin 1", "1 is", "is the", "the major", "structural component", "of microfibrils.", "microfibrils. fibrillin", "fibrillin 2", "2 is", "expressed earlier", "earlier in", "in development", "development than", "than fibrillin", "1 and", "and may", "may be", "be important", "important for", "for elastic", "elastic fiber", "fiber formation", "zhang et", "al. 1994", "1994 .", ". fibrillin", "fibrillin 3", "3 arose", "arose as", "a duplication", "duplication of", "2 that", "that did", "did not", "not occur", "occur in", "the rodent", "rodent lineage.", "lineage. it", "it was", "was first", "first isolated", "isolated from", "from human", "human brain", "corson et", "2004 .

              fibrillin", ".

              fibrillin assembly", "assembly is", "is not", "not as", "well defined", "defined as", "as elastin", "elastin assembly.", "assembly. the", "the primary", "primary structure", "structure of", "fibrillin is", "is dominated", "dominated by", "by calcium", "calcium binding", "binding epidermal", "epidermal growth", "growth factor", "factor like", "like repeats", "kielty et", "fibrillin may", "may form", "form dimers", "dimers or", "or trimers", "trimers before", "before secretion.", "secretion. however", "multimerisation predominantly", "predominantly occurs", "occurs outside", "outside the", "the cell.", "cell. formation", "of fibrils", "fibrils appears", "to require", "require cell", "cell surface", "surface structures", "structures suggesting", "suggesting an", "an involvement", "involvement of", "of cell", "surface receptors.", "receptors. fibrillin", "is assembled", "assembled pericellularly", "i.e. on", "on or", "or close", "close to", "to the", "the cell", "into microfibrillar", "microfibrillar arrays", "arrays that", "that undergo", "undergo time", "time dependent", "dependent maturation", "maturation into", "into microfibrils", "with beaded", "beaded string", "string appearance.", "appearance. transglutaminase", "transglutaminase forms", "forms gamma", "gamma glutamyl", "glutamyl epsilon", "epsilon lysine", "lysine isopeptide", "isopeptide bonds", "bonds within", "within or", "or between", "between peptide", "peptide chains.", "chains. additionally", "intermolecular disulfide", "disulfide bond", "bond formation", "formation between", "between fibrillins", "fibrillins is", "is an", "an important", "important contributor", "contributor to", "to fibril", "fibril maturation", "reinhardt et", "al. 2000", "2000 .

              models", ".

              models of", "1 microfibril", "microfibril structure", "structure suggest", "suggest that", "that the", "the n", "terminal half", "half of", "is asymmetrically", "asymmetrically exposed", "exposed in", "in outer", "outer filaments", "while the", "the c", "c terminal", "half is", "is buried", "buried in", "the interior", "kuo et", "al. 2007", "2007 .", ". fibrillinopathies", "fibrillinopathies include", "include marfan", "marfan syndrome", "familial ectopia", "ectopia lentis", "familial thoracic", "thoracic aneurysm", "all due", "due to", "to mutations", "mutations in", "the fibrillin", "1 gene", "gene fbn1", "and congenital", "congenital contractural", "contractural arachnodactyly", "arachnodactyly which", "which is", "is caused", "caused by", "by mutation", "mutation of", "of fbn2", "maslen &", "& glanville", "glanville 1993", "davis &", "& summers", "summers 2012", "2012 .

              in", ".

              in vivo", "vivo assembly", "assembly of", "fibrillin requires", "requires the", "the presence", "presence of", "of extracellular", "extracellular fibronectin", "fibronectin fibres", "sabatier et", "al. 2009", "2009 .", ". fibrillins", "fibrillins have", "have arg", "arg gly", "gly asp", "sequences that", "that interact", "interact with", "with integrins", "pfaff et", "al. 1996", "sakamoto et", "bax et", "jovanovic et", "al. 2008", "and heparin", "heparin binding", "binding domains", "domains that", "with a", "a cell", "surface heparan", "heparan sulfate", "sulfate proteoglycan", "tiedemann et", "al. 2001", "possibly a", "a syndecan", "ritty et", "fibrillins also", "also have", "have a", "major role", "in binding", "binding and", "and sequestering", "sequestering growth", "growth factors", "factors such", "as tgf", "beta into", "into the", "the ecm", "neptune et", ". proteoglycans", "proteoglycans such", "as versican", "isogai et", "and decorin", "reinboth et", "can interact", "the microfibrils.", "microfibrils. they", "they confer", "confer specific", "specific properties", "properties including", "including hydration", "impact absorption", "molecular sieving", "regulation of", "of cellular", "cellular activities", "mediation of", "of growth", "factor association", "and release", "release and", "and transport", "transport within", "within the", "the extracellular", "extracellular matrix", "buczek thomas", "thomas et", "glycosaminoglycans have", "have been", "to interact", "with tropoelastin", "tropoelastin through", "through its", "its lysine", "lysine side", "side chains", "wu et", "al. 1999", "regulating tropoelastin", "tropoelastin assembly", "tu &", "& weiss", "weiss 2008", "2008 .

              elastin", ".

              elastin is", "is synthesized", "synthesized as", "a 70kda", "70kda monomer", "monomer called", "called tropoelastin", "a highly", "highly hydrophobic", "hydrophobic protein", "protein composed", "of two", "two types", "types of", "of domains", "that alternate", "alternate along", "along the", "the polypeptide", "polypeptide chain.", "chain. hydrophobic", "hydrophobic domains", "domains are", "are rich", "rich in", "in glycine", "leucine and", "and valine.", "valine. these", "these amino", "amino acids", "acids occur", "in characteristic", "characteristic short", "3 9", "9 amino", "tandem repeats", "a flexible", "flexible and", "and highly", "highly dynamic", "dynamic structure", "floquet et", ". unlike", "unlike collagen", "glycine in", "in elastin", "elastin is", "not rigorously", "rigorously positioned", "positioned every", "every 3", "3 residues.", "residues. however", "glycine is", "is distributed", "distributed frequently", "frequently throughout", "throughout all", "all hydrophobic", "domains of", "and displays", "displays a", "a strong", "strong preference", "preference for", "for inter", "inter glycine", "glycine spacing", "spacing of", "of 0", "0 3", "3 residues", "rauscher et", "al. 2006", "2006 .", ".

              elastic", "

              elastic fibre", "formation involves", "involves the", "the deposition", "deposition of", "of tropoelastin", "tropoelastin onto", "onto a", "a template", "template of", "fibrillin rich", "rich microfibrils.", "microfibrils. recent", "recent results", "results suggest", "the first", "first step", "step of", "formation is", "the organization", "organization of", "of small", "small globules", "globules of", "elastin on", "on the", "surface followed", "followed by", "by globule", "globule aggregation", "aggregation into", "into microfibres", "kozel et", ". an", "important contribution", "contribution to", "the initial", "initial stages", "stages assembly", "is thought", "thought to", "to be", "be made", "made by", "by the", "the intrinsic", "intrinsic ability", "ability of", "the protein", "protein to", "to direct", "direct its", "its own", "own polymeric", "polymeric organization", "organization in", "in a", "a process", "process termed", "termed 'coacervation'", "al. 1986", "1986 .", ". this", "this self", "self assembly", "assembly process", "process appears", "be determined", "determined by", "by interactions", "between hydrophobic", "vrhovski et", "al. 1997", "bellingham et", "cirulis &", "& keeley", "keeley 2010", "which result", "result in", "in alignment", "alignment of", "the cross", "cross linking", "linking domains", "allowing the", "the stabilization", "stabilization of", "elastin through", "through the", "of cross", "cross links", "links generated", "generated through", "the oxidative", "oxidative deamination", "deamination of", "of lysine", "lysine residues", "catalyzed by", "by members", "members of", "the lysyl", "lysyl oxidase", "reiser et", "al. 1992", "mithieux &", "weiss 2005", ". the", "step in", "linking reaction", "reaction is", "oxidative formation", "the delta", "delta aldehyde", "known as", "as alpha", "alpha aminoadipic", "aminoadipic semialdehyde", "semialdehyde or", "or allysine", "partridge 1963", "1963 .", ". subsequent", "subsequent reactions", "reactions that", "that are", "are probably", "probably spontaneous", "spontaneous lead", "lead to", "links through", "through dehydrolysinonorleucine", "dehydrolysinonorleucine and", "and allysine", "allysine aldol", "a trifunctional", "trifunctional cross", "cross link", "link dehydromerodesmosine", "dehydromerodesmosine and", "and two", "two tetrafunctional", "tetrafunctional cross", "links desmosine", "desmosine and", "and isodesmosine", "lucero &", "& kagan", "kagan 2006", "are unique", "unique to", "to elastin.", "elastin. these", "these cross", "links confer", "confer mechanical", "mechanical integrity", "integrity and", "and high", "high durability.", "durability. in", "to their", "their role", "in self", "domains provide", "provide elastin", "elastin with", "with its", "its elastomeric", "elastomeric properties", "with initial", "initial studies", "studies suggesting", "suggesting that", "the elastomeric", "elastomeric propereties", "propereties of", "are driven", "driven through", "through changes", "changes in", "in entropic", "entropic interactions", "with surrounding", "surrounding water", "water molecules", "hoeve &", "& flory", "flory 1974", "1974 .", ".

              a", "

              a very", "very specific", "specific set", "set of", "of proteases", "broadly grouped", "grouped under", "under the", "the name", "name elastases", "is responsible", "responsible for", "for elastin", "elastin remodelling", "antonicelli et", "the matrix", "matrix metalloproteinases", "are particularly", "particularly important", "important in", "elastin breakdown", "with mmp2", "9 and", "and 12", "12 explicitly", "explicitly shown", "to degrade", "degrade elastin", "ra &", "& parks", "parks 2007", ". nonetheless", "elastin typically", "typically displays", "a low", "low turnover", "turnover rate", "rate under", "under normal", "normal conditions", "conditions over", "over a", "a lifetime", "davis 1993", "fibres ef", "are a major", "a major structural", "major structural constituent", "structural constituent of", "constituent of dynamic", "of dynamic connective", "dynamic connective tissues", "connective tissues such", "tissues such as", "such as large", "as large arteries", "large arteries and", "arteries and lung", "and lung parenchyma", "parenchyma where", "where they provide", "they provide essential", "provide essential properties", "essential properties of", "properties of elastic", "of elastic recoil", "elastic recoil and", "recoil and resilience.", "and resilience. ef", "resilience. ef are", "ef are composed", "are composed of", "composed of a", "of a central", "a central cross", "central cross linked", "cross linked core", "linked core of", "core of elastin", "elastin surrounded", "surrounded by a", "by a mesh", "a mesh of", "mesh of microfibrils", "microfibrils which", "which are composed", "are composed largely", "composed largely of", "largely of fibrillin.", "of fibrillin. in", "fibrillin. in addition", "in addition to", "addition to elastin", "to elastin and", "elastin and fibrillin", "and fibrillin 1", "1 over", "over 30 ancillary", "30 ancillary proteins", "ancillary proteins are", "proteins are involved", "are involved in", "involved in mediating", "in mediating important", "mediating important roles", "important roles in", "roles in elastic", "in elastic fibre", "elastic fibre assembly", "fibre assembly as", "assembly as well", "as well as", "well as interactions", "as interactions with", "interactions with the", "with the surrounding", "the surrounding environment.", "surrounding environment. these", "environment. these include", "these include fibulins", "fibulins elastin", "elastin microfibril interface", "microfibril interface located", "interface located proteins", "proteins emilins", "microfibril associated glycoproteins", "glycoproteins magps", "magps and", "and latent tgf", "latent tgf beta", "tgf beta binding", "beta binding proteins", "proteins ltbps", "ltbps . fibulin", ". fibulin 5", "fibulin 5 for", "5 for example", "example is", "is expressed by", "expressed by vascular", "by vascular smooth", "vascular smooth muscle", "smooth muscle cells", "muscle cells and", "cells and plays", "and plays an", "plays an essential", "an essential role", "essential role in", "role in the", "in the formation", "the formation of", "formation of elastic", "of elastic fibres", "elastic fibres through", "fibres through mediating", "through mediating interactions", "mediating interactions between", "interactions between elastin", "between elastin and", "fibrillin yanigasawa", "yanigasawa et al.", "et al. 2002", "2002 freeman", "freeman et al.", "et al. 2005", "al. 2005 .", "2005 . in", ". in addition", "addition it", "it plays a", "plays a role", "a role in", "role in cell", "in cell adhesion", "cell adhesion through", "adhesion through integrin", "through integrin receptors", "integrin receptors and", "receptors and has", "and has been", "has been shown", "been shown to", "shown to influence", "to influence smooth", "influence smooth muscle", "smooth muscle cell", "muscle cell proliferation", "proliferation yanigasawa", "2002 nakamura", "nakamura et al.", "al. 2002 .", "2002 . emilins", ". emilins are", "emilins are a", "are a family", "a family of", "family of homologous", "of homologous glycoproteins", "homologous glycoproteins originally", "glycoproteins originally identified", "originally identified in", "identified in extracts", "in extracts of", "extracts of aortas.", "of aortas. found", "aortas. found at", "found at the", "at the elastin", "the elastin fibrillin", "elastin fibrillin interface", "interface early", "early studies showed", "studies showed that", "showed that antibodies", "that antibodies to", "antibodies to emilin", "to emilin can", "emilin can affect", "can affect the", "affect the process", "the process of", "process of elastic", "of elastic fibre", "formation bressan", "bressan et al.", "et al. 1993", "al. 1993 .", "1993 . emilin1", ". emilin1 has", "emilin1 has been", "shown to bind", "to bind elastin", "bind elastin and", "elastin and fibulin", "and fibulin 5", "fibulin 5 and", "5 and appears", "and appears to", "appears to coordinate", "to coordinate their", "coordinate their common", "their common interaction", "interaction zanetti", "zanetti et al.", "et al. 2004", "al. 2004 .", "2004 . magps", ". magps are", "magps are found", "are found to", "found to co", "to co localize", "co localize with", "localize with microfibrils.", "with microfibrils. magp", "microfibrils. magp 1", "1 for", "example binds", "binds strongly to", "strongly to an", "to an n", "an n terminal", "n terminal sequence", "terminal sequence of", "sequence of fibrillin", "of fibrillin 1.", "fibrillin 1. other", "1. other proteins", "other proteins found", "proteins found associated", "found associated with", "associated with microfibrils", "with microfibrils include", "microfibrils include vitronectin", "vitronectin dahlback", "dahlback et al.", "et al. 1990", "al. 1990 .

              fibrillin", "1990 .

              fibrillin is", ".

              fibrillin is most", "is most familiar", "most familiar as", "familiar as a", "as a component", "a component of", "component of elastic", "elastic fibres but", "fibres but microfibrils", "but microfibrils with", "microfibrils with no", "with no elastin", "no elastin are", "elastin are found", "are found in", "found in the", "in the ciliary", "the ciliary zonules", "ciliary zonules of", "zonules of the", "of the eye", "the eye and", "eye and invertebrate", "and invertebrate circulatory", "invertebrate circulatory systems.", "circulatory systems. the", "systems. the addition", "the addition of", "addition of elastin", "of elastin to", "elastin to microfibrils", "to microfibrils is", "microfibrils is a", "is a vertebrate", "a vertebrate adaptation", "vertebrate adaptation to", "adaptation to high", "to high pulsatile", "high pulsatile pressures", "pulsatile pressures in", "pressures in their", "in their closed", "their closed circulatory", "closed circulatory systems", "systems faury", "faury et al.", "et al. 2003", "al. 2003 .", "2003 . elastin", ". elastin appears", "elastin appears to", "appears to have", "to have emerged", "have emerged after", "emerged after the", "after the divergence", "the divergence of", "divergence of jawless", "of jawless vertebrates", "jawless vertebrates from", "vertebrates from other", "from other vertebrates", "vertebrates sage", "sage 1982 .", "1982 .

              fibrillin", ".

              fibrillin 1", "

              fibrillin 1 is", "1 is the", "is the major", "the major structural", "major structural component", "structural component of", "component of microfibrils.", "of microfibrils. fibrillin", "microfibrils. fibrillin 2", "fibrillin 2 is", "2 is expressed", "is expressed earlier", "expressed earlier in", "earlier in development", "in development than", "development than fibrillin", "than fibrillin 1", "fibrillin 1 and", "1 and may", "and may be", "may be important", "be important for", "important for elastic", "for elastic fiber", "elastic fiber formation", "formation zhang", "zhang et al.", "et al. 1994", "al. 1994 .", "1994 . fibrillin", ". fibrillin 3", "fibrillin 3 arose", "3 arose as", "arose as a", "as a duplication", "a duplication of", "duplication of fibrillin", "of fibrillin 2", "fibrillin 2 that", "2 that did", "that did not", "did not occur", "not occur in", "occur in the", "in the rodent", "the rodent lineage.", "rodent lineage. it", "lineage. it was", "it was first", "was first isolated", "first isolated from", "isolated from human", "from human brain", "brain corson", "corson et al.", "al. 2004 .

              fibrillin", "2004 .

              fibrillin assembly", ".

              fibrillin assembly is", "assembly is not", "is not as", "not as well", "as well defined", "well defined as", "defined as elastin", "as elastin assembly.", "elastin assembly. the", "assembly. the primary", "the primary structure", "primary structure of", "structure of fibrillin", "of fibrillin is", "fibrillin is dominated", "is dominated by", "dominated by calcium", "by calcium binding", "calcium binding epidermal", "binding epidermal growth", "epidermal growth factor", "growth factor like", "factor like repeats", "repeats kielty", "kielty et al.", "2002 . fibrillin", ". fibrillin may", "fibrillin may form", "may form dimers", "form dimers or", "dimers or trimers", "or trimers before", "trimers before secretion.", "before secretion. however", "however multimerisation", "multimerisation predominantly occurs", "predominantly occurs outside", "occurs outside the", "outside the cell.", "the cell. formation", "cell. formation of", "formation of fibrils", "of fibrils appears", "fibrils appears to", "appears to require", "to require cell", "require cell surface", "cell surface structures", "surface structures suggesting", "structures suggesting an", "suggesting an involvement", "an involvement of", "involvement of cell", "of cell surface", "cell surface receptors.", "surface receptors. fibrillin", "receptors. fibrillin is", "fibrillin is assembled", "is assembled pericellularly", "pericellularly i.e.", "i.e. on or", "on or close", "or close to", "close to the", "to the cell", "the cell surface", "surface into", "into microfibrillar arrays", "microfibrillar arrays that", "arrays that undergo", "that undergo time", "undergo time dependent", "time dependent maturation", "dependent maturation into", "maturation into microfibrils", "into microfibrils with", "microfibrils with beaded", "with beaded string", "beaded string appearance.", "string appearance. transglutaminase", "appearance. transglutaminase forms", "transglutaminase forms gamma", "forms gamma glutamyl", "gamma glutamyl epsilon", "glutamyl epsilon lysine", "epsilon lysine isopeptide", "lysine isopeptide bonds", "isopeptide bonds within", "bonds within or", "within or between", "or between peptide", "between peptide chains.", "peptide chains. additionally", "additionally intermolecular", "intermolecular disulfide bond", "disulfide bond formation", "bond formation between", "formation between fibrillins", "between fibrillins is", "fibrillins is an", "is an important", "an important contributor", "important contributor to", "contributor to fibril", "to fibril maturation", "maturation reinhardt", "reinhardt et al.", "et al. 2000", "al. 2000 .

              models", "2000 .

              models of", ".

              models of fibrillin", "of fibrillin 1", "fibrillin 1 microfibril", "1 microfibril structure", "microfibril structure suggest", "structure suggest that", "suggest that the", "that the n", "the n terminal", "n terminal half", "terminal half of", "half of fibrillin", "fibrillin 1 is", "1 is asymmetrically", "is asymmetrically exposed", "asymmetrically exposed in", "exposed in outer", "in outer filaments", "filaments while", "while the c", "the c terminal", "c terminal half", "terminal half is", "half is buried", "is buried in", "buried in the", "in the interior", "interior kuo", "kuo et al.", "et al. 2007", "al. 2007 .", "2007 . fibrillinopathies", ". fibrillinopathies include", "fibrillinopathies include marfan", "include marfan syndrome", "syndrome familial", "familial ectopia lentis", "lentis familial", "familial thoracic aneurysm", "aneurysm all", "all due to", "due to mutations", "to mutations in", "mutations in the", "in the fibrillin", "the fibrillin 1", "fibrillin 1 gene", "1 gene fbn1", "and congenital contractural", "congenital contractural arachnodactyly", "contractural arachnodactyly which", "arachnodactyly which is", "which is caused", "is caused by", "caused by mutation", "by mutation of", "mutation of fbn2", "fbn2 maslen", "maslen & glanville", "& glanville 1993", "1993 davis", "davis & summers", "& summers 2012", "summers 2012 .

              in", "2012 .

              in vivo", ".

              in vivo assembly", "vivo assembly of", "assembly of fibrillin", "of fibrillin requires", "fibrillin requires the", "requires the presence", "the presence of", "presence of extracellular", "of extracellular fibronectin", "extracellular fibronectin fibres", "fibres sabatier", "sabatier et al.", "et al. 2009", "al. 2009 .", "2009 . fibrillins", ". fibrillins have", "fibrillins have arg", "have arg gly", "arg gly asp", "asp rgd", "rgd sequences", "sequences that interact", "that interact with", "interact with integrins", "integrins pfaff", "pfaff et al.", "et al. 1996", "1996 sakamoto", "sakamoto et al.", "1996 bax", "bax et al.", "2003 jovanovic", "jovanovic et al.", "et al. 2008", "2008 and", "and heparin binding", "heparin binding domains", "binding domains that", "domains that interact", "interact with a", "with a cell", "a cell surface", "cell surface heparan", "surface heparan sulfate", "heparan sulfate proteoglycan", "proteoglycan tiedemann", "tiedemann et al.", "et al. 2001", "2001 possibly", "possibly a syndecan", "syndecan ritty", "ritty et al.", "2003 . fibrillins", ". fibrillins also", "fibrillins also have", "also have a", "have a major", "a major role", "major role in", "role in binding", "in binding and", "binding and sequestering", "and sequestering growth", "sequestering growth factors", "growth factors such", "factors such as", "such as tgf", "as tgf beta", "tgf beta into", "beta into the", "into the ecm", "neptune et al.", "2003 . proteoglycans", ". proteoglycans such", "proteoglycans such as", "such as versican", "versican isogai", "isogai et al.", "biglycan and", "decorin reinboth", "reinboth et al.", "2002 can", "can interact with", "interact with the", "with the microfibrils.", "the microfibrils. they", "microfibrils. they confer", "they confer specific", "confer specific properties", "specific properties including", "properties including hydration", "hydration impact", "absorption molecular", "sieving regulation", "regulation of cellular", "of cellular activities", "activities mediation", "mediation of growth", "of growth factor", "growth factor association", "association and", "and release and", "release and transport", "and transport within", "transport within the", "within the extracellular", "the extracellular matrix", "matrix buczek", "buczek thomas et", "thomas et al.", "2002 . in", "addition glycosaminoglycans", "glycosaminoglycans have been", "have been shown", "shown to interact", "to interact with", "interact with tropoelastin", "with tropoelastin through", "tropoelastin through its", "through its lysine", "its lysine side", "lysine side chains", "chains wu", "wu et al.", "et al. 1999", "regulating tropoelastin assembly", "assembly tu", "tu & weiss", "& weiss 2008", "weiss 2008 .

              elastin", "2008 .

              elastin is", ".

              elastin is synthesized", "is synthesized as", "synthesized as a", "as a 70kda", "a 70kda monomer", "70kda monomer called", "monomer called tropoelastin", "tropoelastin a", "a highly hydrophobic", "highly hydrophobic protein", "hydrophobic protein composed", "protein composed largely", "largely of two", "of two types", "two types of", "types of domains", "of domains that", "domains that alternate", "that alternate along", "alternate along the", "along the polypeptide", "the polypeptide chain.", "polypeptide chain. hydrophobic", "chain. hydrophobic domains", "hydrophobic domains are", "domains are rich", "are rich in", "rich in glycine", "glycine proline", "proline alanine", "alanine leucine", "leucine and valine.", "and valine. these", "valine. these amino", "these amino acids", "amino acids occur", "acids occur in", "occur in characteristic", "in characteristic short", "short 3", "3 9 amino", "9 amino acids", "acids tandem", "repeats with", "with a flexible", "a flexible and", "flexible and highly", "and highly dynamic", "highly dynamic structure", "structure floquet", "floquet et al.", "2004 . unlike", ". unlike collagen", "collagen glycine", "glycine in elastin", "in elastin is", "elastin is not", "is not rigorously", "not rigorously positioned", "rigorously positioned every", "positioned every 3", "every 3 residues.", "3 residues. however", "however glycine", "glycine is distributed", "is distributed frequently", "distributed frequently throughout", "frequently throughout all", "throughout all hydrophobic", "all hydrophobic domains", "hydrophobic domains of", "domains of elastin", "and displays a", "displays a strong", "a strong preference", "strong preference for", "preference for inter", "for inter glycine", "inter glycine spacing", "glycine spacing of", "spacing of 0", "of 0 3", "0 3 residues", "residues rauscher", "rauscher et al.", "et al. 2006", "al. 2006 .", "2006 .

              elastic", ".

              elastic fibre", "

              elastic fibre formation", "fibre formation involves", "formation involves the", "involves the deposition", "the deposition of", "deposition of tropoelastin", "of tropoelastin onto", "tropoelastin onto a", "onto a template", "a template of", "template of fibrillin", "of fibrillin rich", "fibrillin rich microfibrils.", "rich microfibrils. recent", "microfibrils. recent results", "recent results suggest", "results suggest that", "that the first", "the first step", "first step of", "step of elastic", "of elastic fiber", "fiber formation is", "formation is the", "is the organization", "the organization of", "organization of small", "of small globules", "small globules of", "globules of elastin", "of elastin on", "elastin on the", "on the cell", "cell surface followed", "surface followed by", "followed by globule", "by globule aggregation", "globule aggregation into", "aggregation into microfibres", "microfibres kozel", "kozel et al.", "2006 . an", ". an important", "an important contribution", "important contribution to", "contribution to the", "to the initial", "the initial stages", "initial stages assembly", "stages assembly is", "assembly is thought", "is thought to", "thought to be", "to be made", "be made by", "made by the", "by the intrinsic", "the intrinsic ability", "intrinsic ability of", "ability of the", "of the protein", "the protein to", "protein to direct", "to direct its", "direct its own", "its own polymeric", "own polymeric organization", "polymeric organization in", "organization in a", "in a process", "a process termed", "process termed 'coacervation'", "'coacervation' bressan", "et al. 1986", "al. 1986 .", "1986 . this", ". this self", "this self assembly", "self assembly process", "assembly process appears", "process appears to", "appears to be", "to be determined", "be determined by", "determined by interactions", "by interactions between", "interactions between hydrophobic", "between hydrophobic domains", "domains bressan", "1986 vrhovski", "vrhovski et al.", "et al. 1997", "bellingham et al.", "2003 cirulis", "cirulis & keeley", "& keeley 2010", "2010 which", "which result in", "result in alignment", "in alignment of", "alignment of the", "of the cross", "the cross linking", "cross linking domains", "domains allowing", "allowing the stabilization", "the stabilization of", "stabilization of elastin", "of elastin through", "elastin through the", "through the formation", "formation of cross", "of cross links", "cross links generated", "links generated through", "generated through the", "through the oxidative", "the oxidative deamination", "oxidative deamination of", "deamination of lysine", "of lysine residues", "residues catalyzed", "catalyzed by members", "by members of", "members of the", "of the lysyl", "the lysyl oxidase", "oxidase lox", "lox family", "family reiser", "reiser et al.", "et al. 1992", "1992 mithieux", "mithieux & weiss", "& weiss 2005", "weiss 2005 .", "2005 . the", ". the first", "first step in", "step in the", "in the cross", "cross linking reaction", "linking reaction is", "reaction is the", "is the oxidative", "the oxidative formation", "oxidative formation of", "formation of the", "of the delta", "the delta aldehyde", "aldehyde known", "known as alpha", "as alpha aminoadipic", "alpha aminoadipic semialdehyde", "aminoadipic semialdehyde or", "semialdehyde or allysine", "allysine partridge", "partridge 1963 .", "1963 . subsequent", ". subsequent reactions", "subsequent reactions that", "reactions that are", "that are probably", "are probably spontaneous", "probably spontaneous lead", "spontaneous lead to", "lead to the", "to the formation", "cross links through", "links through dehydrolysinonorleucine", "through dehydrolysinonorleucine and", "dehydrolysinonorleucine and allysine", "and allysine aldol", "aldol a", "a trifunctional cross", "trifunctional cross link", "cross link dehydromerodesmosine", "link dehydromerodesmosine and", "dehydromerodesmosine and two", "and two tetrafunctional", "two tetrafunctional cross", "tetrafunctional cross links", "cross links desmosine", "links desmosine and", "desmosine and isodesmosine", "isodesmosine lucero", "lucero & kagan", "& kagan 2006", "which are unique", "are unique to", "unique to elastin.", "to elastin. these", "elastin. these cross", "these cross links", "cross links confer", "links confer mechanical", "confer mechanical integrity", "mechanical integrity and", "integrity and high", "and high durability.", "high durability. in", "durability. in addition", "addition to their", "to their role", "their role in", "role in self", "in self assembly", "assembly hydrophobic", "hydrophobic domains provide", "domains provide elastin", "provide elastin with", "elastin with its", "with its elastomeric", "its elastomeric properties", "properties with", "with initial studies", "initial studies suggesting", "studies suggesting that", "suggesting that the", "that the elastomeric", "the elastomeric propereties", "elastomeric propereties of", "propereties of elastin", "of elastin are", "elastin are driven", "are driven through", "driven through changes", "through changes in", "changes in entropic", "in entropic interactions", "entropic interactions with", "interactions with surrounding", "with surrounding water", "surrounding water molecules", "molecules hoeve", "hoeve & flory", "& flory 1974", "flory 1974 .", "1974 .

              a", ".

              a very", "

              a very specific", "very specific set", "specific set of", "set of proteases", "proteases broadly", "broadly grouped under", "grouped under the", "under the name", "the name elastases", "elastases is", "is responsible for", "responsible for elastin", "for elastin remodelling", "remodelling antonicelli", "antonicelli et al.", "2007 . the", ". the matrix", "the matrix metalloproteinases", "metalloproteinases mmps", "mmps are", "are particularly important", "particularly important in", "important in elastin", "in elastin breakdown", "breakdown with", "mmp2 3", "9 and 12", "and 12 explicitly", "12 explicitly shown", "explicitly shown to", "shown to degrade", "to degrade elastin", "elastin ra", "ra & parks", "& parks 2007", "parks 2007 .", "2007 . nonetheless", "nonetheless elastin", "elastin typically displays", "typically displays a", "displays a low", "a low turnover", "low turnover rate", "turnover rate under", "rate under normal", "under normal conditions", "normal conditions over", "conditions over a", "over a lifetime", "lifetime davis", "davis 1993 .", "elastic fibres ef", "ef are a", "are a major structural", "a major structural constituent", "major structural constituent of", "structural constituent of dynamic", "constituent of dynamic connective", "of dynamic connective tissues", "dynamic connective tissues such", "connective tissues such as", "tissues such as large", "such as large arteries", "as large arteries and", "large arteries and lung", "arteries and lung parenchyma", "lung parenchyma where", "parenchyma where they", "where they provide essential", "they provide essential properties", "provide essential properties of", "essential properties of elastic", "properties of elastic recoil", "of elastic recoil and", "elastic recoil and resilience.", "recoil and resilience. ef", "and resilience. ef are", "resilience. ef are composed", "ef are composed of", "are composed of a", "composed of a central", "of a central cross", "a central cross linked", "central cross linked core", "cross linked core of", "linked core of elastin", "of elastin surrounded", "elastin surrounded by", "surrounded by a mesh", "by a mesh of", "a mesh of microfibrils", "of microfibrils which", "microfibrils which are", "which are composed largely", "are composed largely of", "composed largely of fibrillin.", "largely of fibrillin. in", "of fibrillin. in addition", "fibrillin. in addition to", "in addition to elastin", "addition to elastin and", "to elastin and fibrillin", "elastin and fibrillin 1", "fibrillin 1 over", "1 over 30", "over 30 ancillary proteins", "30 ancillary proteins are", "ancillary proteins are involved", "proteins are involved in", "are involved in mediating", "involved in mediating important", "in mediating important roles", "mediating important roles in", "important roles in elastic", "roles in elastic fibre", "in elastic fibre assembly", "elastic fibre assembly as", "fibre assembly as well", "assembly as well as", "as well as interactions", "well as interactions with", "as interactions with the", "interactions with the surrounding", "with the surrounding environment.", "the surrounding environment. these", "surrounding environment. these include", "environment. these include fibulins", "include fibulins elastin", "fibulins elastin microfibril", "elastin microfibril interface located", "microfibril interface located proteins", "located proteins emilins", "emilins microfibril", "associated glycoproteins magps", "magps and latent", "and latent tgf beta", "latent tgf beta binding", "tgf beta binding proteins", "binding proteins ltbps", "proteins ltbps .", "ltbps . fibulin 5", ". fibulin 5 for", "fibulin 5 for example", "for example is", "example is expressed", "is expressed by vascular", "expressed by vascular smooth", "by vascular smooth muscle", "vascular smooth muscle cells", "smooth muscle cells and", "muscle cells and plays", "cells and plays an", "and plays an essential", "plays an essential role", "an essential role in", "essential role in the", "role in the formation", "in the formation of", "the formation of elastic", "formation of elastic fibres", "of elastic fibres through", "elastic fibres through mediating", "fibres through mediating interactions", "through mediating interactions between", "mediating interactions between elastin", "interactions between elastin and", "between elastin and fibrillin", "and fibrillin yanigasawa", "fibrillin yanigasawa et", "yanigasawa et al. 2002", "al. 2002 freeman", "2002 freeman et", "freeman et al. 2005", "et al. 2005 .", "al. 2005 . in", "2005 . in addition", "in addition it", "addition it plays", "it plays a role", "plays a role in", "a role in cell", "role in cell adhesion", "in cell adhesion through", "cell adhesion through integrin", "adhesion through integrin receptors", "through integrin receptors and", "integrin receptors and has", "receptors and has been", "and has been shown", "has been shown to", "been shown to influence", "shown to influence smooth", "to influence smooth muscle", "influence smooth muscle cell", "smooth muscle cell proliferation", "cell proliferation yanigasawa", "proliferation yanigasawa et", "al. 2002 nakamura", "2002 nakamura et", "nakamura et al. 2002", "et al. 2002 .", "al. 2002 . emilins", "2002 . emilins are", ". emilins are a", "emilins are a family", "are a family of", "a family of homologous", "family of homologous glycoproteins", "of homologous glycoproteins originally", "homologous glycoproteins originally identified", "glycoproteins originally identified in", "originally identified in extracts", "identified in extracts of", "in extracts of aortas.", "extracts of aortas. found", "of aortas. found at", "aortas. found at the", "found at the elastin", "at the elastin fibrillin", "the elastin fibrillin interface", "fibrillin interface early", "interface early studies", "early studies showed that", "studies showed that antibodies", "showed that antibodies to", "that antibodies to emilin", "antibodies to emilin can", "to emilin can affect", "emilin can affect the", "can affect the process", "affect the process of", "the process of elastic", "process of elastic fibre", "of elastic fibre formation", "fibre formation bressan", "formation bressan et", "bressan et al. 1993", "et al. 1993 .", "al. 1993 . emilin1", "1993 . emilin1 has", ". emilin1 has been", "emilin1 has been shown", "been shown to bind", "shown to bind elastin", "to bind elastin and", "bind elastin and fibulin", "elastin and fibulin 5", "and fibulin 5 and", "fibulin 5 and appears", "5 and appears to", "and appears to coordinate", "appears to coordinate their", "to coordinate their common", "coordinate their common interaction", "common interaction zanetti", "interaction zanetti et", "zanetti et al. 2004", "et al. 2004 .", "al. 2004 . magps", "2004 . magps are", ". magps are found", "magps are found to", "are found to co", "found to co localize", "to co localize with", "co localize with microfibrils.", "localize with microfibrils. magp", "with microfibrils. magp 1", "magp 1 for", "1 for example", "for example binds", "example binds strongly", "binds strongly to an", "strongly to an n", "to an n terminal", "an n terminal sequence", "n terminal sequence of", "terminal sequence of fibrillin", "sequence of fibrillin 1.", "of fibrillin 1. other", "fibrillin 1. other proteins", "1. other proteins found", "other proteins found associated", "proteins found associated with", "found associated with microfibrils", "associated with microfibrils include", "with microfibrils include vitronectin", "include vitronectin dahlback", "vitronectin dahlback et", "dahlback et al. 1990", "et al. 1990 .

              fibrillin", "al. 1990 .

              fibrillin is", "1990 .

              fibrillin is most", ".

              fibrillin is most familiar", "is most familiar as", "most familiar as a", "familiar as a component", "as a component of", "a component of elastic", "component of elastic fibres", "of elastic fibres but", "elastic fibres but microfibrils", "fibres but microfibrils with", "but microfibrils with no", "microfibrils with no elastin", "with no elastin are", "no elastin are found", "elastin are found in", "are found in the", "found in the ciliary", "in the ciliary zonules", "the ciliary zonules of", "ciliary zonules of the", "zonules of the eye", "of the eye and", "the eye and invertebrate", "eye and invertebrate circulatory", "and invertebrate circulatory systems.", "invertebrate circulatory systems. the", "circulatory systems. the addition", "systems. the addition of", "the addition of elastin", "addition of elastin to", "of elastin to microfibrils", "elastin to microfibrils is", "to microfibrils is a", "microfibrils is a vertebrate", "is a vertebrate adaptation", "a vertebrate adaptation to", "vertebrate adaptation to high", "adaptation to high pulsatile", "to high pulsatile pressures", "high pulsatile pressures in", "pulsatile pressures in their", "pressures in their closed", "in their closed circulatory", "their closed circulatory systems", "circulatory systems faury", "systems faury et", "faury et al. 2003", "et al. 2003 .", "al. 2003 . elastin", "2003 . elastin appears", ". elastin appears to", "elastin appears to have", "appears to have emerged", "to have emerged after", "have emerged after the", "emerged after the divergence", "after the divergence of", "the divergence of jawless", "divergence of jawless vertebrates", "of jawless vertebrates from", "jawless vertebrates from other", "vertebrates from other vertebrates", "other vertebrates sage", "vertebrates sage 1982", "sage 1982 .

              fibrillin", "1982 .

              fibrillin 1", ".

              fibrillin 1 is", "

              fibrillin 1 is the", "1 is the major", "is the major structural", "the major structural component", "major structural component of", "structural component of microfibrils.", "component of microfibrils. fibrillin", "of microfibrils. fibrillin 2", "microfibrils. fibrillin 2 is", "fibrillin 2 is expressed", "2 is expressed earlier", "is expressed earlier in", "expressed earlier in development", "earlier in development than", "in development than fibrillin", "development than fibrillin 1", "than fibrillin 1 and", "fibrillin 1 and may", "1 and may be", "and may be important", "may be important for", "be important for elastic", "important for elastic fiber", "for elastic fiber formation", "fiber formation zhang", "formation zhang et", "zhang et al. 1994", "et al. 1994 .", "al. 1994 . fibrillin", "1994 . fibrillin 3", ". fibrillin 3 arose", "fibrillin 3 arose as", "3 arose as a", "arose as a duplication", "as a duplication of", "a duplication of fibrillin", "duplication of fibrillin 2", "of fibrillin 2 that", "fibrillin 2 that did", "2 that did not", "that did not occur", "did not occur in", "not occur in the", "occur in the rodent", "in the rodent lineage.", "the rodent lineage. it", "rodent lineage. it was", "lineage. it was first", "it was first isolated", "was first isolated from", "first isolated from human", "isolated from human brain", "human brain corson", "brain corson et", "corson et al. 2004", "et al. 2004 .

              fibrillin", "al. 2004 .

              fibrillin assembly", "2004 .

              fibrillin assembly is", ".

              fibrillin assembly is not", "assembly is not as", "is not as well", "not as well defined", "as well defined as", "well defined as elastin", "defined as elastin assembly.", "as elastin assembly. the", "elastin assembly. the primary", "assembly. the primary structure", "the primary structure of", "primary structure of fibrillin", "structure of fibrillin is", "of fibrillin is dominated", "fibrillin is dominated by", "is dominated by calcium", "dominated by calcium binding", "by calcium binding epidermal", "calcium binding epidermal growth", "binding epidermal growth factor", "epidermal growth factor like", "growth factor like repeats", "like repeats kielty", "repeats kielty et", "kielty et al. 2002", "al. 2002 . fibrillin", "2002 . fibrillin may", ". fibrillin may form", "fibrillin may form dimers", "may form dimers or", "form dimers or trimers", "dimers or trimers before", "or trimers before secretion.", "trimers before secretion. however", "secretion. however multimerisation", "however multimerisation predominantly", "multimerisation predominantly occurs outside", "predominantly occurs outside the", "occurs outside the cell.", "outside the cell. formation", "the cell. formation of", "cell. formation of fibrils", "formation of fibrils appears", "of fibrils appears to", "fibrils appears to require", "appears to require cell", "to require cell surface", "require cell surface structures", "cell surface structures suggesting", "surface structures suggesting an", "structures suggesting an involvement", "suggesting an involvement of", "an involvement of cell", "involvement of cell surface", "of cell surface receptors.", "cell surface receptors. fibrillin", "surface receptors. fibrillin is", "receptors. fibrillin is assembled", "fibrillin is assembled pericellularly", "assembled pericellularly i.e.", "pericellularly i.e. on", "i.e. on or close", "on or close to", "or close to the", "close to the cell", "to the cell surface", "cell surface into", "surface into microfibrillar", "into microfibrillar arrays that", "microfibrillar arrays that undergo", "arrays that undergo time", "that undergo time dependent", "undergo time dependent maturation", "time dependent maturation into", "dependent maturation into microfibrils", "maturation into microfibrils with", "into microfibrils with beaded", "microfibrils with beaded string", "with beaded string appearance.", "beaded string appearance. transglutaminase", "string appearance. transglutaminase forms", "appearance. transglutaminase forms gamma", "transglutaminase forms gamma glutamyl", "forms gamma glutamyl epsilon", "gamma glutamyl epsilon lysine", "glutamyl epsilon lysine isopeptide", "epsilon lysine isopeptide bonds", "lysine isopeptide bonds within", "isopeptide bonds within or", "bonds within or between", "within or between peptide", "or between peptide chains.", "between peptide chains. additionally", "chains. additionally intermolecular", "additionally intermolecular disulfide", "intermolecular disulfide bond formation", "disulfide bond formation between", "bond formation between fibrillins", "formation between fibrillins is", "between fibrillins is an", "fibrillins is an important", "is an important contributor", "an important contributor to", "important contributor to fibril", "contributor to fibril maturation", "fibril maturation reinhardt", "maturation reinhardt et", "reinhardt et al. 2000", "et al. 2000 .

              models", "al. 2000 .

              models of", "2000 .

              models of fibrillin", ".

              models of fibrillin 1", "of fibrillin 1 microfibril", "fibrillin 1 microfibril structure", "1 microfibril structure suggest", "microfibril structure suggest that", "structure suggest that the", "suggest that the n", "that the n terminal", "the n terminal half", "n terminal half of", "terminal half of fibrillin", "half of fibrillin 1", "of fibrillin 1 is", "fibrillin 1 is asymmetrically", "1 is asymmetrically exposed", "is asymmetrically exposed in", "asymmetrically exposed in outer", "exposed in outer filaments", "outer filaments while", "filaments while the", "while the c terminal", "the c terminal half", "c terminal half is", "terminal half is buried", "half is buried in", "is buried in the", "buried in the interior", "the interior kuo", "interior kuo et", "kuo et al. 2007", "et al. 2007 .", "al. 2007 . fibrillinopathies", "2007 . fibrillinopathies include", ". fibrillinopathies include marfan", "fibrillinopathies include marfan syndrome", "marfan syndrome familial", "syndrome familial ectopia", "ectopia lentis familial", "lentis familial thoracic", "thoracic aneurysm all", "aneurysm all due", "all due to mutations", "due to mutations in", "to mutations in the", "mutations in the fibrillin", "in the fibrillin 1", "the fibrillin 1 gene", "fibrillin 1 gene fbn1", "fbn1 and", "and congenital contractural arachnodactyly", "congenital contractural arachnodactyly which", "contractural arachnodactyly which is", "arachnodactyly which is caused", "which is caused by", "is caused by mutation", "caused by mutation of", "by mutation of fbn2", "of fbn2 maslen", "fbn2 maslen &", "maslen & glanville 1993", "glanville 1993 davis", "1993 davis &", "davis & summers 2012", "& summers 2012 .

              in", "summers 2012 .

              in vivo", "2012 .

              in vivo assembly", ".

              in vivo assembly of", "vivo assembly of fibrillin", "assembly of fibrillin requires", "of fibrillin requires the", "fibrillin requires the presence", "requires the presence of", "the presence of extracellular", "presence of extracellular fibronectin", "of extracellular fibronectin fibres", "fibronectin fibres sabatier", "fibres sabatier et", "sabatier et al. 2009", "et al. 2009 .", "al. 2009 . fibrillins", "2009 . fibrillins have", ". fibrillins have arg", "fibrillins have arg gly", "have arg gly asp", "gly asp rgd", "rgd sequences that", "sequences that interact with", "that interact with integrins", "with integrins pfaff", "integrins pfaff et", "pfaff et al. 1996", "al. 1996 sakamoto", "1996 sakamoto et", "sakamoto et al. 1996", "al. 1996 bax", "1996 bax et", "2003 jovanovic et", "jovanovic et al. 2008", "al. 2008 and", "2008 and heparin", "and heparin binding domains", "heparin binding domains that", "binding domains that interact", "domains that interact with", "that interact with a", "interact with a cell", "with a cell surface", "a cell surface heparan", "cell surface heparan sulfate", "surface heparan sulfate proteoglycan", "sulfate proteoglycan tiedemann", "proteoglycan tiedemann et", "tiedemann et al. 2001", "al. 2001 possibly", "2001 possibly a", "a syndecan ritty", "syndecan ritty et", "ritty et al. 2003", "al. 2003 . fibrillins", "2003 . fibrillins also", ". fibrillins also have", "fibrillins also have a", "also have a major", "have a major role", "a major role in", "major role in binding", "role in binding and", "in binding and sequestering", "binding and sequestering growth", "and sequestering growth factors", "sequestering growth factors such", "growth factors such as", "factors such as tgf", "such as tgf beta", "as tgf beta into", "tgf beta into the", "beta into the ecm", "ecm neptune", "neptune et al. 2003", "al. 2003 . proteoglycans", "2003 . proteoglycans such", ". proteoglycans such as", "proteoglycans such as versican", "as versican isogai", "versican isogai et", "isogai et al. 2002", "2002 biglycan", "biglycan and decorin", "and decorin reinboth", "decorin reinboth et", "reinboth et al. 2002", "al. 2002 can", "2002 can interact", "can interact with the", "interact with the microfibrils.", "with the microfibrils. they", "the microfibrils. they confer", "microfibrils. they confer specific", "they confer specific properties", "confer specific properties including", "specific properties including hydration", "including hydration impact", "hydration impact absorption", "impact absorption molecular", "absorption molecular sieving", "molecular sieving regulation", "sieving regulation of", "regulation of cellular activities", "cellular activities mediation", "activities mediation of", "mediation of growth factor", "of growth factor association", "factor association and", "association and release", "and release and transport", "release and transport within", "and transport within the", "transport within the extracellular", "within the extracellular matrix", "extracellular matrix buczek", "matrix buczek thomas", "buczek thomas et al.", "thomas et al. 2002", "al. 2002 . in", "2002 . in addition", "in addition glycosaminoglycans", "addition glycosaminoglycans have", "glycosaminoglycans have been shown", "have been shown to", "been shown to interact", "shown to interact with", "to interact with tropoelastin", "interact with tropoelastin through", "with tropoelastin through its", "tropoelastin through its lysine", "through its lysine side", "its lysine side chains", "side chains wu", "chains wu et", "wu et al. 1999", "1999 regulating", "tropoelastin assembly tu", "assembly tu &", "tu & weiss 2008", "& weiss 2008 .

              elastin", "weiss 2008 .

              elastin is", "2008 .

              elastin is synthesized", ".

              elastin is synthesized as", "is synthesized as a", "synthesized as a 70kda", "as a 70kda monomer", "a 70kda monomer called", "70kda monomer called tropoelastin", "called tropoelastin a", "tropoelastin a highly", "a highly hydrophobic protein", "highly hydrophobic protein composed", "hydrophobic protein composed largely", "protein composed largely of", "composed largely of two", "largely of two types", "of two types of", "two types of domains", "types of domains that", "of domains that alternate", "domains that alternate along", "that alternate along the", "alternate along the polypeptide", "along the polypeptide chain.", "the polypeptide chain. hydrophobic", "polypeptide chain. hydrophobic domains", "chain. hydrophobic domains are", "hydrophobic domains are rich", "domains are rich in", "are rich in glycine", "in glycine proline", "alanine leucine and", "leucine and valine. these", "and valine. these amino", "valine. these amino acids", "these amino acids occur", "amino acids occur in", "acids occur in characteristic", "occur in characteristic short", "characteristic short 3", "short 3 9", "3 9 amino acids", "amino acids tandem", "acids tandem repeats", "tandem repeats with", "repeats with a", "with a flexible and", "a flexible and highly", "flexible and highly dynamic", "and highly dynamic structure", "dynamic structure floquet", "structure floquet et", "floquet et al. 2004", "al. 2004 . unlike", "2004 . unlike collagen", "unlike collagen glycine", "collagen glycine in", "glycine in elastin is", "in elastin is not", "elastin is not rigorously", "is not rigorously positioned", "not rigorously positioned every", "rigorously positioned every 3", "positioned every 3 residues.", "every 3 residues. however", "residues. however glycine", "however glycine is", "glycine is distributed frequently", "is distributed frequently throughout", "distributed frequently throughout all", "frequently throughout all hydrophobic", "throughout all hydrophobic domains", "all hydrophobic domains of", "hydrophobic domains of elastin", "of elastin and", "elastin and displays", "and displays a strong", "displays a strong preference", "a strong preference for", "strong preference for inter", "preference for inter glycine", "for inter glycine spacing", "inter glycine spacing of", "glycine spacing of 0", "spacing of 0 3", "of 0 3 residues", "3 residues rauscher", "residues rauscher et", "rauscher et al. 2006", "et al. 2006 .", "al. 2006 .

              elastic", "2006 .

              elastic fibre", ".

              elastic fibre formation", "

              elastic fibre formation involves", "fibre formation involves the", "formation involves the deposition", "involves the deposition of", "the deposition of tropoelastin", "deposition of tropoelastin onto", "of tropoelastin onto a", "tropoelastin onto a template", "onto a template of", "a template of fibrillin", "template of fibrillin rich", "of fibrillin rich microfibrils.", "fibrillin rich microfibrils. recent", "rich microfibrils. recent results", "microfibrils. recent results suggest", "recent results suggest that", "results suggest that the", "suggest that the first", "that the first step", "the first step of", "first step of elastic", "step of elastic fiber", "of elastic fiber formation", "elastic fiber formation is", "fiber formation is the", "formation is the organization", "is the organization of", "the organization of small", "organization of small globules", "of small globules of", "small globules of elastin", "globules of elastin on", "of elastin on the", "elastin on the cell", "on the cell surface", "the cell surface followed", "cell surface followed by", "surface followed by globule", "followed by globule aggregation", "by globule aggregation into", "globule aggregation into microfibres", "into microfibres kozel", "microfibres kozel et", "kozel et al. 2006", "al. 2006 . an", "2006 . an important", ". an important contribution", "an important contribution to", "important contribution to the", "contribution to the initial", "to the initial stages", "the initial stages assembly", "initial stages assembly is", "stages assembly is thought", "assembly is thought to", "is thought to be", "thought to be made", "to be made by", "be made by the", "made by the intrinsic", "by the intrinsic ability", "the intrinsic ability of", "intrinsic ability of the", "ability of the protein", "of the protein to", "the protein to direct", "protein to direct its", "to direct its own", "direct its own polymeric", "its own polymeric organization", "own polymeric organization in", "polymeric organization in a", "organization in a process", "in a process termed", "a process termed 'coacervation'", "termed 'coacervation' bressan", "'coacervation' bressan et", "bressan et al. 1986", "et al. 1986 .", "al. 1986 . this", "1986 . this self", ". this self assembly", "this self assembly process", "self assembly process appears", "assembly process appears to", "process appears to be", "appears to be determined", "to be determined by", "be determined by interactions", "determined by interactions between", "by interactions between hydrophobic", "interactions between hydrophobic domains", "hydrophobic domains bressan", "domains bressan et", "al. 1986 vrhovski", "1986 vrhovski et", "vrhovski et al. 1997", "1997 bellingham", "bellingham et al. 2003", "al. 2003 cirulis", "2003 cirulis &", "cirulis & keeley 2010", "keeley 2010 which", "2010 which result", "which result in alignment", "result in alignment of", "in alignment of the", "alignment of the cross", "of the cross linking", "the cross linking domains", "linking domains allowing", "domains allowing the", "allowing the stabilization of", "the stabilization of elastin", "stabilization of elastin through", "of elastin through the", "elastin through the formation", "through the formation of", "the formation of cross", "formation of cross links", "of cross links generated", "cross links generated through", "links generated through the", "generated through the oxidative", "through the oxidative deamination", "the oxidative deamination of", "oxidative deamination of lysine", "deamination of lysine residues", "lysine residues catalyzed", "residues catalyzed by", "catalyzed by members of", "by members of the", "members of the lysyl", "of the lysyl oxidase", "lysyl oxidase lox", "family reiser et", "reiser et al. 1992", "al. 1992 mithieux", "1992 mithieux &", "mithieux & weiss 2005", "& weiss 2005 .", "weiss 2005 . the", "2005 . the first", ". the first step", "the first step in", "first step in the", "step in the cross", "in the cross linking", "the cross linking reaction", "cross linking reaction is", "linking reaction is the", "reaction is the oxidative", "is the oxidative formation", "the oxidative formation of", "oxidative formation of the", "formation of the delta", "of the delta aldehyde", "delta aldehyde known", "aldehyde known as", "known as alpha aminoadipic", "as alpha aminoadipic semialdehyde", "alpha aminoadipic semialdehyde or", "aminoadipic semialdehyde or allysine", "or allysine partridge", "allysine partridge 1963", "partridge 1963 . subsequent", "1963 . subsequent reactions", ". subsequent reactions that", "subsequent reactions that are", "reactions that are probably", "that are probably spontaneous", "are probably spontaneous lead", "probably spontaneous lead to", "spontaneous lead to the", "lead to the formation", "to the formation of", "of cross links through", "cross links through dehydrolysinonorleucine", "links through dehydrolysinonorleucine and", "through dehydrolysinonorleucine and allysine", "dehydrolysinonorleucine and allysine aldol", "allysine aldol a", "aldol a trifunctional", "a trifunctional cross link", "trifunctional cross link dehydromerodesmosine", "cross link dehydromerodesmosine and", "link dehydromerodesmosine and two", "dehydromerodesmosine and two tetrafunctional", "and two tetrafunctional cross", "two tetrafunctional cross links", "tetrafunctional cross links desmosine", "cross links desmosine and", "links desmosine and isodesmosine", "and isodesmosine lucero", "isodesmosine lucero &", "lucero & kagan 2006", "2006 which", "which are unique to", "are unique to elastin.", "unique to elastin. these", "to elastin. these cross", "elastin. these cross links", "these cross links confer", "cross links confer mechanical", "links confer mechanical integrity", "confer mechanical integrity and", "mechanical integrity and high", "integrity and high durability.", "and high durability. in", "high durability. in addition", "durability. in addition to", "in addition to their", "addition to their role", "to their role in", "their role in self", "role in self assembly", "self assembly hydrophobic", "assembly hydrophobic domains", "hydrophobic domains provide elastin", "domains provide elastin with", "provide elastin with its", "elastin with its elastomeric", "with its elastomeric properties", "elastomeric properties with", "properties with initial", "with initial studies suggesting", "initial studies suggesting that", "studies suggesting that the", "suggesting that the elastomeric", "that the elastomeric propereties", "the elastomeric propereties of", "elastomeric propereties of elastin", "propereties of elastin are", "of elastin are driven", "elastin are driven through", "are driven through changes", "driven through changes in", "through changes in entropic", "changes in entropic interactions", "in entropic interactions with", "entropic interactions with surrounding", "interactions with surrounding water", "with surrounding water molecules", "water molecules hoeve", "molecules hoeve &", "hoeve & flory 1974", "& flory 1974 .", "flory 1974 .

              a", "1974 .

              a very", ".

              a very specific", "

              a very specific set", "very specific set of", "specific set of proteases", "of proteases broadly", "proteases broadly grouped", "broadly grouped under the", "grouped under the name", "under the name elastases", "name elastases is", "elastases is responsible", "is responsible for elastin", "responsible for elastin remodelling", "elastin remodelling antonicelli", "remodelling antonicelli et", "antonicelli et al. 2007", "al. 2007 . the", "2007 . the matrix", ". the matrix metalloproteinases", "matrix metalloproteinases mmps", "mmps are particularly", "are particularly important in", "particularly important in elastin", "important in elastin breakdown", "elastin breakdown with", "breakdown with mmp2", "with mmp2 3", "3 9 and", "9 and 12 explicitly", "and 12 explicitly shown", "12 explicitly shown to", "explicitly shown to degrade", "shown to degrade elastin", "degrade elastin ra", "elastin ra &", "ra & parks 2007", "& parks 2007 .", "parks 2007 . nonetheless", ". nonetheless elastin", "nonetheless elastin typically", "elastin typically displays a", "typically displays a low", "displays a low turnover", "a low turnover rate", "low turnover rate under", "turnover rate under normal", "rate under normal conditions", "under normal conditions over", "normal conditions over a", "conditions over a lifetime", "a lifetime davis", "lifetime davis 1993", "fibres ef are", "ef are a major", "are a major structural constituent", "a major structural constituent of", "major structural constituent of dynamic", "structural constituent of dynamic connective", "constituent of dynamic connective tissues", "of dynamic connective tissues such", "dynamic connective tissues such as", "connective tissues such as large", "tissues such as large arteries", "such as large arteries and", "as large arteries and lung", "large arteries and lung parenchyma", "and lung parenchyma where", "lung parenchyma where they", "parenchyma where they provide", "where they provide essential properties", "they provide essential properties of", "provide essential properties of elastic", "essential properties of elastic recoil", "properties of elastic recoil and", "of elastic recoil and resilience.", "elastic recoil and resilience. ef", "recoil and resilience. ef are", "and resilience. ef are composed", "resilience. ef are composed of", "ef are composed of a", "are composed of a central", "composed of a central cross", "of a central cross linked", "a central cross linked core", "central cross linked core of", "cross linked core of elastin", "core of elastin surrounded", "of elastin surrounded by", "elastin surrounded by a", "surrounded by a mesh of", "by a mesh of microfibrils", "mesh of microfibrils which", "of microfibrils which are", "microfibrils which are composed", "which are composed largely of", "are composed largely of fibrillin.", "composed largely of fibrillin. in", "largely of fibrillin. in addition", "of fibrillin. in addition to", "fibrillin. in addition to elastin", "in addition to elastin and", "addition to elastin and fibrillin", "to elastin and fibrillin 1", "and fibrillin 1 over", "fibrillin 1 over 30", "1 over 30 ancillary", "over 30 ancillary proteins are", "30 ancillary proteins are involved", "ancillary proteins are involved in", "proteins are involved in mediating", "are involved in mediating important", "involved in mediating important roles", "in mediating important roles in", "mediating important roles in elastic", "important roles in elastic fibre", "roles in elastic fibre assembly", "in elastic fibre assembly as", "elastic fibre assembly as well", "fibre assembly as well as", "assembly as well as interactions", "as well as interactions with", "well as interactions with the", "as interactions with the surrounding", "interactions with the surrounding environment.", "with the surrounding environment. these", "the surrounding environment. these include", "surrounding environment. these include fibulins", "these include fibulins elastin", "include fibulins elastin microfibril", "fibulins elastin microfibril interface", "elastin microfibril interface located proteins", "interface located proteins emilins", "emilins microfibril associated", "microfibril associated glycoproteins magps", "glycoproteins magps and", "magps and latent tgf", "and latent tgf beta binding", "latent tgf beta binding proteins", "beta binding proteins ltbps", "binding proteins ltbps .", "proteins ltbps . fibulin", "ltbps . fibulin 5 for", ". fibulin 5 for example", "5 for example is", "for example is expressed", "example is expressed by", "is expressed by vascular smooth", "expressed by vascular smooth muscle", "by vascular smooth muscle cells", "vascular smooth muscle cells and", "smooth muscle cells and plays", "muscle cells and plays an", "cells and plays an essential", "and plays an essential role", "plays an essential role in", "an essential role in the", "essential role in the formation", "role in the formation of", "in the formation of elastic", "the formation of elastic fibres", "formation of elastic fibres through", "of elastic fibres through mediating", "elastic fibres through mediating interactions", "fibres through mediating interactions between", "through mediating interactions between elastin", "mediating interactions between elastin and", "interactions between elastin and fibrillin", "elastin and fibrillin yanigasawa", "and fibrillin yanigasawa et", "fibrillin yanigasawa et al.", "et al. 2002 freeman", "al. 2002 freeman et", "2002 freeman et al.", "freeman et al. 2005 .", "et al. 2005 . in", "al. 2005 . in addition", ". in addition it", "in addition it plays", "addition it plays a", "it plays a role in", "plays a role in cell", "a role in cell adhesion", "role in cell adhesion through", "in cell adhesion through integrin", "cell adhesion through integrin receptors", "adhesion through integrin receptors and", "through integrin receptors and has", "integrin receptors and has been", "receptors and has been shown", "and has been shown to", "has been shown to influence", "been shown to influence smooth", "shown to influence smooth muscle", "to influence smooth muscle cell", "influence smooth muscle cell proliferation", "muscle cell proliferation yanigasawa", "cell proliferation yanigasawa et", "proliferation yanigasawa et al.", "et al. 2002 nakamura", "al. 2002 nakamura et", "2002 nakamura et al.", "nakamura et al. 2002 .", "et al. 2002 . emilins", "al. 2002 . emilins are", "2002 . emilins are a", ". emilins are a family", "emilins are a family of", "are a family of homologous", "a family of homologous glycoproteins", "family of homologous glycoproteins originally", "of homologous glycoproteins originally identified", "homologous glycoproteins originally identified in", "glycoproteins originally identified in extracts", "originally identified in extracts of", "identified in extracts of aortas.", "in extracts of aortas. found", "extracts of aortas. found at", "of aortas. found at the", "aortas. found at the elastin", "found at the elastin fibrillin", "at the elastin fibrillin interface", "elastin fibrillin interface early", "fibrillin interface early studies", "interface early studies showed", "early studies showed that antibodies", "studies showed that antibodies to", "showed that antibodies to emilin", "that antibodies to emilin can", "antibodies to emilin can affect", "to emilin can affect the", "emilin can affect the process", "can affect the process of", "affect the process of elastic", "the process of elastic fibre", "process of elastic fibre formation", "elastic fibre formation bressan", "fibre formation bressan et", "formation bressan et al.", "bressan et al. 1993 .", "et al. 1993 . emilin1", "al. 1993 . emilin1 has", "1993 . emilin1 has been", ". emilin1 has been shown", "emilin1 has been shown to", "has been shown to bind", "been shown to bind elastin", "shown to bind elastin and", "to bind elastin and fibulin", "bind elastin and fibulin 5", "elastin and fibulin 5 and", "and fibulin 5 and appears", "fibulin 5 and appears to", "5 and appears to coordinate", "and appears to coordinate their", "appears to coordinate their common", "to coordinate their common interaction", "their common interaction zanetti", "common interaction zanetti et", "interaction zanetti et al.", "zanetti et al. 2004 .", "et al. 2004 . magps", "al. 2004 . magps are", "2004 . magps are found", ". magps are found to", "magps are found to co", "are found to co localize", "found to co localize with", "to co localize with microfibrils.", "co localize with microfibrils. magp", "localize with microfibrils. magp 1", "microfibrils. magp 1 for", "magp 1 for example", "for example binds strongly", "example binds strongly to", "binds strongly to an n", "strongly to an n terminal", "to an n terminal sequence", "an n terminal sequence of", "n terminal sequence of fibrillin", "terminal sequence of fibrillin 1.", "sequence of fibrillin 1. other", "of fibrillin 1. other proteins", "fibrillin 1. other proteins found", "1. other proteins found associated", "other proteins found associated with", "proteins found associated with microfibrils", "found associated with microfibrils include", "associated with microfibrils include vitronectin", "microfibrils include vitronectin dahlback", "include vitronectin dahlback et", "vitronectin dahlback et al.", "dahlback et al. 1990 .

              fibrillin", "et al. 1990 .

              fibrillin is", "al. 1990 .

              fibrillin is most", "1990 .

              fibrillin is most familiar", ".

              fibrillin is most familiar as", "is most familiar as a", "most familiar as a component", "familiar as a component of", "as a component of elastic", "a component of elastic fibres", "component of elastic fibres but", "of elastic fibres but microfibrils", "elastic fibres but microfibrils with", "fibres but microfibrils with no", "but microfibrils with no elastin", "microfibrils with no elastin are", "with no elastin are found", "no elastin are found in", "elastin are found in the", "are found in the ciliary", "found in the ciliary zonules", "in the ciliary zonules of", "the ciliary zonules of the", "ciliary zonules of the eye", "zonules of the eye and", "of the eye and invertebrate", "the eye and invertebrate circulatory", "eye and invertebrate circulatory systems.", "and invertebrate circulatory systems. the", "invertebrate circulatory systems. the addition", "circulatory systems. the addition of", "systems. the addition of elastin", "the addition of elastin to", "addition of elastin to microfibrils", "of elastin to microfibrils is", "elastin to microfibrils is a", "to microfibrils is a vertebrate", "microfibrils is a vertebrate adaptation", "is a vertebrate adaptation to", "a vertebrate adaptation to high", "vertebrate adaptation to high pulsatile", "adaptation to high pulsatile pressures", "to high pulsatile pressures in", "high pulsatile pressures in their", "pulsatile pressures in their closed", "pressures in their closed circulatory", "in their closed circulatory systems", "closed circulatory systems faury", "circulatory systems faury et", "systems faury et al.", "faury et al. 2003 .", "et al. 2003 . elastin", "al. 2003 . elastin appears", "2003 . elastin appears to", ". elastin appears to have", "elastin appears to have emerged", "appears to have emerged after", "to have emerged after the", "have emerged after the divergence", "emerged after the divergence of", "after the divergence of jawless", "the divergence of jawless vertebrates", "divergence of jawless vertebrates from", "of jawless vertebrates from other", "jawless vertebrates from other vertebrates", "from other vertebrates sage", "other vertebrates sage 1982", "vertebrates sage 1982 .", "sage 1982 .

              fibrillin 1", "1982 .

              fibrillin 1 is", ".

              fibrillin 1 is the", "

              fibrillin 1 is the major", "1 is the major structural", "is the major structural component", "the major structural component of", "major structural component of microfibrils.", "structural component of microfibrils. fibrillin", "component of microfibrils. fibrillin 2", "of microfibrils. fibrillin 2 is", "microfibrils. fibrillin 2 is expressed", "fibrillin 2 is expressed earlier", "2 is expressed earlier in", "is expressed earlier in development", "expressed earlier in development than", "earlier in development than fibrillin", "in development than fibrillin 1", "development than fibrillin 1 and", "than fibrillin 1 and may", "fibrillin 1 and may be", "1 and may be important", "and may be important for", "may be important for elastic", "be important for elastic fiber", "important for elastic fiber formation", "elastic fiber formation zhang", "fiber formation zhang et", "formation zhang et al.", "zhang et al. 1994 .", "et al. 1994 . fibrillin", "al. 1994 . fibrillin 3", "1994 . fibrillin 3 arose", ". fibrillin 3 arose as", "fibrillin 3 arose as a", "3 arose as a duplication", "arose as a duplication of", "as a duplication of fibrillin", "a duplication of fibrillin 2", "duplication of fibrillin 2 that", "of fibrillin 2 that did", "fibrillin 2 that did not", "2 that did not occur", "that did not occur in", "did not occur in the", "not occur in the rodent", "occur in the rodent lineage.", "in the rodent lineage. it", "the rodent lineage. it was", "rodent lineage. it was first", "lineage. it was first isolated", "it was first isolated from", "was first isolated from human", "first isolated from human brain", "from human brain corson", "human brain corson et", "brain corson et al.", "corson et al. 2004 .

              fibrillin", "et al. 2004 .

              fibrillin assembly", "al. 2004 .

              fibrillin assembly is", "2004 .

              fibrillin assembly is not", ".

              fibrillin assembly is not as", "assembly is not as well", "is not as well defined", "not as well defined as", "as well defined as elastin", "well defined as elastin assembly.", "defined as elastin assembly. the", "as elastin assembly. the primary", "elastin assembly. the primary structure", "assembly. the primary structure of", "the primary structure of fibrillin", "primary structure of fibrillin is", "structure of fibrillin is dominated", "of fibrillin is dominated by", "fibrillin is dominated by calcium", "is dominated by calcium binding", "dominated by calcium binding epidermal", "by calcium binding epidermal growth", "calcium binding epidermal growth factor", "binding epidermal growth factor like", "epidermal growth factor like repeats", "factor like repeats kielty", "like repeats kielty et", "repeats kielty et al.", "kielty et al. 2002 .", "et al. 2002 . fibrillin", "al. 2002 . fibrillin may", "2002 . fibrillin may form", ". fibrillin may form dimers", "fibrillin may form dimers or", "may form dimers or trimers", "form dimers or trimers before", "dimers or trimers before secretion.", "or trimers before secretion. however", "before secretion. however multimerisation", "secretion. however multimerisation predominantly", "however multimerisation predominantly occurs", "multimerisation predominantly occurs outside the", "predominantly occurs outside the cell.", "occurs outside the cell. formation", "outside the cell. formation of", "the cell. formation of fibrils", "cell. formation of fibrils appears", "formation of fibrils appears to", "of fibrils appears to require", "fibrils appears to require cell", "appears to require cell surface", "to require cell surface structures", "require cell surface structures suggesting", "cell surface structures suggesting an", "surface structures suggesting an involvement", "structures suggesting an involvement of", "suggesting an involvement of cell", "an involvement of cell surface", "involvement of cell surface receptors.", "of cell surface receptors. fibrillin", "cell surface receptors. fibrillin is", "surface receptors. fibrillin is assembled", "receptors. fibrillin is assembled pericellularly", "is assembled pericellularly i.e.", "assembled pericellularly i.e. on", "pericellularly i.e. on or", "i.e. on or close to", "on or close to the", "or close to the cell", "close to the cell surface", "the cell surface into", "cell surface into microfibrillar", "surface into microfibrillar arrays", "into microfibrillar arrays that undergo", "microfibrillar arrays that undergo time", "arrays that undergo time dependent", "that undergo time dependent maturation", "undergo time dependent maturation into", "time dependent maturation into microfibrils", "dependent maturation into microfibrils with", "maturation into microfibrils with beaded", "into microfibrils with beaded string", "microfibrils with beaded string appearance.", "with beaded string appearance. transglutaminase", "beaded string appearance. transglutaminase forms", "string appearance. transglutaminase forms gamma", "appearance. transglutaminase forms gamma glutamyl", "transglutaminase forms gamma glutamyl epsilon", "forms gamma glutamyl epsilon lysine", "gamma glutamyl epsilon lysine isopeptide", "glutamyl epsilon lysine isopeptide bonds", "epsilon lysine isopeptide bonds within", "lysine isopeptide bonds within or", "isopeptide bonds within or between", "bonds within or between peptide", "within or between peptide chains.", "or between peptide chains. additionally", "peptide chains. additionally intermolecular", "chains. additionally intermolecular disulfide", "additionally intermolecular disulfide bond", "intermolecular disulfide bond formation between", "disulfide bond formation between fibrillins", "bond formation between fibrillins is", "formation between fibrillins is an", "between fibrillins is an important", "fibrillins is an important contributor", "is an important contributor to", "an important contributor to fibril", "important contributor to fibril maturation", "to fibril maturation reinhardt", "fibril maturation reinhardt et", "maturation reinhardt et al.", "reinhardt et al. 2000 .

              models", "et al. 2000 .

              models of", "al. 2000 .

              models of fibrillin", "2000 .

              models of fibrillin 1", ".

              models of fibrillin 1 microfibril", "of fibrillin 1 microfibril structure", "fibrillin 1 microfibril structure suggest", "1 microfibril structure suggest that", "microfibril structure suggest that the", "structure suggest that the n", "suggest that the n terminal", "that the n terminal half", "the n terminal half of", "n terminal half of fibrillin", "terminal half of fibrillin 1", "half of fibrillin 1 is", "of fibrillin 1 is asymmetrically", "fibrillin 1 is asymmetrically exposed", "1 is asymmetrically exposed in", "is asymmetrically exposed in outer", "asymmetrically exposed in outer filaments", "in outer filaments while", "outer filaments while the", "filaments while the c", "while the c terminal half", "the c terminal half is", "c terminal half is buried", "terminal half is buried in", "half is buried in the", "is buried in the interior", "in the interior kuo", "the interior kuo et", "interior kuo et al.", "kuo et al. 2007 .", "et al. 2007 . fibrillinopathies", "al. 2007 . fibrillinopathies include", "2007 . fibrillinopathies include marfan", ". fibrillinopathies include marfan syndrome", "include marfan syndrome familial", "marfan syndrome familial ectopia", "syndrome familial ectopia lentis", "familial ectopia lentis familial", "ectopia lentis familial thoracic", "lentis familial thoracic aneurysm", "familial thoracic aneurysm all", "thoracic aneurysm all due", "aneurysm all due to", "all due to mutations in", "due to mutations in the", "to mutations in the fibrillin", "mutations in the fibrillin 1", "in the fibrillin 1 gene", "the fibrillin 1 gene fbn1", "gene fbn1 and", "fbn1 and congenital", "and congenital contractural arachnodactyly which", "congenital contractural arachnodactyly which is", "contractural arachnodactyly which is caused", "arachnodactyly which is caused by", "which is caused by mutation", "is caused by mutation of", "caused by mutation of fbn2", "mutation of fbn2 maslen", "of fbn2 maslen &", "fbn2 maslen & glanville", "& glanville 1993 davis", "glanville 1993 davis &", "1993 davis & summers", "davis & summers 2012 .

              in", "& summers 2012 .

              in vivo", "summers 2012 .

              in vivo assembly", "2012 .

              in vivo assembly of", ".

              in vivo assembly of fibrillin", "vivo assembly of fibrillin requires", "assembly of fibrillin requires the", "of fibrillin requires the presence", "fibrillin requires the presence of", "requires the presence of extracellular", "the presence of extracellular fibronectin", "presence of extracellular fibronectin fibres", "extracellular fibronectin fibres sabatier", "fibronectin fibres sabatier et", "fibres sabatier et al.", "sabatier et al. 2009 .", "et al. 2009 . fibrillins", "al. 2009 . fibrillins have", "2009 . fibrillins have arg", ". fibrillins have arg gly", "fibrillins have arg gly asp", "arg gly asp rgd", "asp rgd sequences", "rgd sequences that interact", "sequences that interact with integrins", "interact with integrins pfaff", "with integrins pfaff et", "integrins pfaff et al.", "et al. 1996 sakamoto", "al. 1996 sakamoto et", "1996 sakamoto et al.", "et al. 1996 bax", "al. 1996 bax et", "1996 bax et al.", "bax et al. 2003", "al. 2003 jovanovic", "2003 jovanovic et al.", "et al. 2008 and", "al. 2008 and heparin", "2008 and heparin binding", "and heparin binding domains that", "heparin binding domains that interact", "binding domains that interact with", "domains that interact with a", "that interact with a cell", "interact with a cell surface", "with a cell surface heparan", "a cell surface heparan sulfate", "cell surface heparan sulfate proteoglycan", "heparan sulfate proteoglycan tiedemann", "sulfate proteoglycan tiedemann et", "proteoglycan tiedemann et al.", "et al. 2001 possibly", "al. 2001 possibly a", "2001 possibly a syndecan", "possibly a syndecan ritty", "a syndecan ritty et", "syndecan ritty et al.", "ritty et al. 2003 .", "et al. 2003 . fibrillins", "al. 2003 . fibrillins also", "2003 . fibrillins also have", ". fibrillins also have a", "fibrillins also have a major", "also have a major role", "have a major role in", "a major role in binding", "major role in binding and", "role in binding and sequestering", "in binding and sequestering growth", "binding and sequestering growth factors", "and sequestering growth factors such", "sequestering growth factors such as", "growth factors such as tgf", "factors such as tgf beta", "such as tgf beta into", "as tgf beta into the", "tgf beta into the ecm", "the ecm neptune", "ecm neptune et", "neptune et al. 2003 .", "et al. 2003 . proteoglycans", "al. 2003 . proteoglycans such", "2003 . proteoglycans such as", ". proteoglycans such as versican", "such as versican isogai", "as versican isogai et", "versican isogai et al.", "al. 2002 biglycan", "and decorin reinboth et", "decorin reinboth et al.", "et al. 2002 can", "al. 2002 can interact", "2002 can interact with", "can interact with the microfibrils.", "interact with the microfibrils. they", "with the microfibrils. they confer", "the microfibrils. they confer specific", "microfibrils. they confer specific properties", "they confer specific properties including", "confer specific properties including hydration", "properties including hydration impact", "including hydration impact absorption", "impact absorption molecular sieving", "molecular sieving regulation of", "sieving regulation of cellular", "of cellular activities mediation", "cellular activities mediation of", "activities mediation of growth", "mediation of growth factor association", "growth factor association and", "factor association and release", "association and release and", "and release and transport within", "release and transport within the", "and transport within the extracellular", "transport within the extracellular matrix", "the extracellular matrix buczek", "extracellular matrix buczek thomas", "matrix buczek thomas et", "buczek thomas et al. 2002", "thomas et al. 2002 .", "et al. 2002 . in", "al. 2002 . in addition", ". in addition glycosaminoglycans", "in addition glycosaminoglycans have", "addition glycosaminoglycans have been", "glycosaminoglycans have been shown to", "have been shown to interact", "been shown to interact with", "shown to interact with tropoelastin", "to interact with tropoelastin through", "interact with tropoelastin through its", "with tropoelastin through its lysine", "tropoelastin through its lysine side", "through its lysine side chains", "lysine side chains wu", "side chains wu et", "chains wu et al.", "al. 1999 regulating", "1999 regulating tropoelastin", "regulating tropoelastin assembly tu", "tropoelastin assembly tu &", "assembly tu & weiss", "tu & weiss 2008 .

              elastin", "& weiss 2008 .

              elastin is", "weiss 2008 .

              elastin is synthesized", "2008 .

              elastin is synthesized as", ".

              elastin is synthesized as a", "is synthesized as a 70kda", "synthesized as a 70kda monomer", "as a 70kda monomer called", "a 70kda monomer called tropoelastin", "monomer called tropoelastin a", "called tropoelastin a highly", "tropoelastin a highly hydrophobic", "a highly hydrophobic protein composed", "highly hydrophobic protein composed largely", "hydrophobic protein composed largely of", "protein composed largely of two", "composed largely of two types", "largely of two types of", "of two types of domains", "two types of domains that", "types of domains that alternate", "of domains that alternate along", "domains that alternate along the", "that alternate along the polypeptide", "alternate along the polypeptide chain.", "along the polypeptide chain. hydrophobic", "the polypeptide chain. hydrophobic domains", "polypeptide chain. hydrophobic domains are", "chain. hydrophobic domains are rich", "hydrophobic domains are rich in", "domains are rich in glycine", "rich in glycine proline", "glycine proline alanine", "proline alanine leucine", "alanine leucine and valine.", "leucine and valine. these amino", "and valine. these amino acids", "valine. these amino acids occur", "these amino acids occur in", "amino acids occur in characteristic", "acids occur in characteristic short", "in characteristic short 3", "characteristic short 3 9", "short 3 9 amino", "9 amino acids tandem", "amino acids tandem repeats", "tandem repeats with a", "repeats with a flexible", "with a flexible and highly", "a flexible and highly dynamic", "flexible and highly dynamic structure", "highly dynamic structure floquet", "dynamic structure floquet et", "structure floquet et al.", "floquet et al. 2004 .", "et al. 2004 . unlike", "al. 2004 . unlike collagen", ". unlike collagen glycine", "unlike collagen glycine in", "collagen glycine in elastin", "glycine in elastin is not", "in elastin is not rigorously", "elastin is not rigorously positioned", "is not rigorously positioned every", "not rigorously positioned every 3", "rigorously positioned every 3 residues.", "positioned every 3 residues. however", "3 residues. however glycine", "residues. however glycine is", "however glycine is distributed", "glycine is distributed frequently throughout", "is distributed frequently throughout all", "distributed frequently throughout all hydrophobic", "frequently throughout all hydrophobic domains", "throughout all hydrophobic domains of", "all hydrophobic domains of elastin", "domains of elastin and", "of elastin and displays", "elastin and displays a", "and displays a strong preference", "displays a strong preference for", "a strong preference for inter", "strong preference for inter glycine", "preference for inter glycine spacing", "for inter glycine spacing of", "inter glycine spacing of 0", "glycine spacing of 0 3", "spacing of 0 3 residues", "0 3 residues rauscher", "3 residues rauscher et", "residues rauscher et al.", "rauscher et al. 2006 .", "et al. 2006 .

              elastic", "al. 2006 .

              elastic fibre", "2006 .

              elastic fibre formation", ".

              elastic fibre formation involves", "

              elastic fibre formation involves the", "fibre formation involves the deposition", "formation involves the deposition of", "involves the deposition of tropoelastin", "the deposition of tropoelastin onto", "deposition of tropoelastin onto a", "of tropoelastin onto a template", "tropoelastin onto a template of", "onto a template of fibrillin", "a template of fibrillin rich", "template of fibrillin rich microfibrils.", "of fibrillin rich microfibrils. recent", "fibrillin rich microfibrils. recent results", "rich microfibrils. recent results suggest", "microfibrils. recent results suggest that", "recent results suggest that the", "results suggest that the first", "suggest that the first step", "that the first step of", "the first step of elastic", "first step of elastic fiber", "step of elastic fiber formation", "of elastic fiber formation is", "elastic fiber formation is the", "fiber formation is the organization", "formation is the organization of", "is the organization of small", "the organization of small globules", "organization of small globules of", "of small globules of elastin", "small globules of elastin on", "globules of elastin on the", "of elastin on the cell", "elastin on the cell surface", "on the cell surface followed", "the cell surface followed by", "cell surface followed by globule", "surface followed by globule aggregation", "followed by globule aggregation into", "by globule aggregation into microfibres", "aggregation into microfibres kozel", "into microfibres kozel et", "microfibres kozel et al.", "kozel et al. 2006 .", "et al. 2006 . an", "al. 2006 . an important", "2006 . an important contribution", ". an important contribution to", "an important contribution to the", "important contribution to the initial", "contribution to the initial stages", "to the initial stages assembly", "the initial stages assembly is", "initial stages assembly is thought", "stages assembly is thought to", "assembly is thought to be", "is thought to be made", "thought to be made by", "to be made by the", "be made by the intrinsic", "made by the intrinsic ability", "by the intrinsic ability of", "the intrinsic ability of the", "intrinsic ability of the protein", "ability of the protein to", "of the protein to direct", "the protein to direct its", "protein to direct its own", "to direct its own polymeric", "direct its own polymeric organization", "its own polymeric organization in", "own polymeric organization in a", "polymeric organization in a process", "organization in a process termed", "in a process termed 'coacervation'", "process termed 'coacervation' bressan", "termed 'coacervation' bressan et", "'coacervation' bressan et al.", "bressan et al. 1986 .", "et al. 1986 . this", "al. 1986 . this self", "1986 . this self assembly", ". this self assembly process", "this self assembly process appears", "self assembly process appears to", "assembly process appears to be", "process appears to be determined", "appears to be determined by", "to be determined by interactions", "be determined by interactions between", "determined by interactions between hydrophobic", "by interactions between hydrophobic domains", "between hydrophobic domains bressan", "hydrophobic domains bressan et", "domains bressan et al.", "et al. 1986 vrhovski", "al. 1986 vrhovski et", "1986 vrhovski et al.", "al. 1997 bellingham", "1997 bellingham et", "et al. 2003 cirulis", "al. 2003 cirulis &", "2003 cirulis & keeley", "& keeley 2010 which", "keeley 2010 which result", "2010 which result in", "which result in alignment of", "result in alignment of the", "in alignment of the cross", "alignment of the cross linking", "of the cross linking domains", "cross linking domains allowing", "linking domains allowing the", "domains allowing the stabilization", "allowing the stabilization of elastin", "the stabilization of elastin through", "stabilization of elastin through the", "of elastin through the formation", "elastin through the formation of", "through the formation of cross", "the formation of cross links", "formation of cross links generated", "of cross links generated through", "cross links generated through the", "links generated through the oxidative", "generated through the oxidative deamination", "through the oxidative deamination of", "the oxidative deamination of lysine", "oxidative deamination of lysine residues", "of lysine residues catalyzed", "lysine residues catalyzed by", "residues catalyzed by members", "catalyzed by members of the", "by members of the lysyl", "members of the lysyl oxidase", "the lysyl oxidase lox", "oxidase lox family", "lox family reiser", "family reiser et al.", "et al. 1992 mithieux", "al. 1992 mithieux &", "1992 mithieux & weiss", "mithieux & weiss 2005 .", "& weiss 2005 . the", "weiss 2005 . the first", "2005 . the first step", ". the first step in", "the first step in the", "first step in the cross", "step in the cross linking", "in the cross linking reaction", "the cross linking reaction is", "cross linking reaction is the", "linking reaction is the oxidative", "reaction is the oxidative formation", "is the oxidative formation of", "the oxidative formation of the", "oxidative formation of the delta", "formation of the delta aldehyde", "the delta aldehyde known", "delta aldehyde known as", "aldehyde known as alpha", "known as alpha aminoadipic semialdehyde", "as alpha aminoadipic semialdehyde or", "alpha aminoadipic semialdehyde or allysine", "semialdehyde or allysine partridge", "or allysine partridge 1963", "allysine partridge 1963 .", "partridge 1963 . subsequent reactions", "1963 . subsequent reactions that", ". subsequent reactions that are", "subsequent reactions that are probably", "reactions that are probably spontaneous", "that are probably spontaneous lead", "are probably spontaneous lead to", "probably spontaneous lead to the", "spontaneous lead to the formation", "lead to the formation of", "to the formation of cross", "formation of cross links through", "of cross links through dehydrolysinonorleucine", "cross links through dehydrolysinonorleucine and", "links through dehydrolysinonorleucine and allysine", "through dehydrolysinonorleucine and allysine aldol", "and allysine aldol a", "allysine aldol a trifunctional", "aldol a trifunctional cross", "a trifunctional cross link dehydromerodesmosine", "trifunctional cross link dehydromerodesmosine and", "cross link dehydromerodesmosine and two", "link dehydromerodesmosine and two tetrafunctional", "dehydromerodesmosine and two tetrafunctional cross", "and two tetrafunctional cross links", "two tetrafunctional cross links desmosine", "tetrafunctional cross links desmosine and", "cross links desmosine and isodesmosine", "desmosine and isodesmosine lucero", "and isodesmosine lucero &", "isodesmosine lucero & kagan", "kagan 2006 which", "2006 which are", "which are unique to elastin.", "are unique to elastin. these", "unique to elastin. these cross", "to elastin. these cross links", "elastin. these cross links confer", "these cross links confer mechanical", "cross links confer mechanical integrity", "links confer mechanical integrity and", "confer mechanical integrity and high", "mechanical integrity and high durability.", "integrity and high durability. in", "and high durability. in addition", "high durability. in addition to", "durability. in addition to their", "in addition to their role", "addition to their role in", "to their role in self", "their role in self assembly", "in self assembly hydrophobic", "self assembly hydrophobic domains", "assembly hydrophobic domains provide", "hydrophobic domains provide elastin with", "domains provide elastin with its", "provide elastin with its elastomeric", "elastin with its elastomeric properties", "its elastomeric properties with", "elastomeric properties with initial", "properties with initial studies", "with initial studies suggesting that", "initial studies suggesting that the", "studies suggesting that the elastomeric", "suggesting that the elastomeric propereties", "that the elastomeric propereties of", "the elastomeric propereties of elastin", "elastomeric propereties of elastin are", "propereties of elastin are driven", "of elastin are driven through", "elastin are driven through changes", "are driven through changes in", "driven through changes in entropic", "through changes in entropic interactions", "changes in entropic interactions with", "in entropic interactions with surrounding", "entropic interactions with surrounding water", "interactions with surrounding water molecules", "surrounding water molecules hoeve", "water molecules hoeve &", "molecules hoeve & flory", "hoeve & flory 1974 .", "& flory 1974 .

              a", "flory 1974 .

              a very", "1974 .

              a very specific", ".

              a very specific set", "

              a very specific set of", "very specific set of proteases", "set of proteases broadly", "of proteases broadly grouped", "proteases broadly grouped under", "broadly grouped under the name", "grouped under the name elastases", "the name elastases is", "name elastases is responsible", "elastases is responsible for", "is responsible for elastin remodelling", "for elastin remodelling antonicelli", "elastin remodelling antonicelli et", "remodelling antonicelli et al.", "antonicelli et al. 2007 .", "et al. 2007 . the", "al. 2007 . the matrix", "2007 . the matrix metalloproteinases", "the matrix metalloproteinases mmps", "metalloproteinases mmps are", "mmps are particularly important", "are particularly important in elastin", "particularly important in elastin breakdown", "in elastin breakdown with", "elastin breakdown with mmp2", "mmp2 3 9", "3 9 and 12", "9 and 12 explicitly shown", "and 12 explicitly shown to", "12 explicitly shown to degrade", "explicitly shown to degrade elastin", "to degrade elastin ra", "degrade elastin ra &", "elastin ra & parks", "ra & parks 2007 .", "& parks 2007 . nonetheless", "2007 . nonetheless elastin", ". nonetheless elastin typically", "nonetheless elastin typically displays", "elastin typically displays a low", "typically displays a low turnover", "displays a low turnover rate", "a low turnover rate under", "low turnover rate under normal", "turnover rate under normal conditions", "rate under normal conditions over", "under normal conditions over a", "normal conditions over a lifetime", "over a lifetime davis", "a lifetime davis 1993", "lifetime davis 1993 ." ] }, { "record_id": "GLY_000594_1_1256", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1566977", "r hsa", "hsa 1566977", "r hsa 1566977" ] }, { "record_id": "GLY_000594_1_1256", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fibronectin matrix", "matrix formation", "fibronectin matrix formation", "is found", "found in", "in the", "the extracellular", "extracellular matrix", "of all", "all cells", "cells as", "as linear", "linear and", "and branched", "branched networks", "networks that", "that surround", "surround and", "and connect", "connect neighbouring", "neighbouring cells", "singh et", "et al.", "al. 2010", "2010 .", ". prior", "prior to", "to matrix", "formation fn1", "fn1 exists", "exists as", "as a", "a protein", "protein dimer.", "dimer. often", "often the", "the two", "two peptide", "peptide chains", "chains represent", "represent differentially", "differentially spliced", "spliced variants.", "variants. the", "the chains", "chains are", "are linked", "linked by", "by a", "a pair", "pair of", "of c", "c terminal", "terminal disulfide", "disulfide bonds", "bonds which", "which are", "are essential", "essential for", "for subsequent", "subsequent multimerization", "schwarzbaur 1991", "1991 .", ". fn1", "fn1 monomers", "monomers have", "have a", "a molecular", "molecular weight", "weight of", "of 230", "230 270", "270 kda", "kda depending", "depending on", "on alternative", "alternative splicing", "splicing and", "and contain", "contain three", "three types", "types of", "of repeating", "repeating unit", "and iii.", "iii. i", "i and", "and ii", "ii are", "are stabilized", "stabilized by", "by intra", "intra chain", "chain disulfide", "disulfide bonds.", "bonds. the", "the absence", "absence of", "of disulfide", "bonds in", "in type", "type iii", "iii modules", "modules allows", "allows them", "them to", "to partially", "partially unfold", "unfold under", "under applied", "applied force", "erickson 2002", "2002 .", ". three", "three regions", "regions of", "of variable", "variable splicing", "splicing occur", "occur along", "along the", "the length", "length of", "of the", "the fn1", "fn1 monomer", "mao &", "& schwarzbauer", "schwarzbauer 2005", "2005 .", ". one", "one or", "or both", "both of", "the 'extra'", "'extra' type", "modules eiiia", "eiiia and", "and eiiib", "eiiib may", "may be", "be present", "present in", "in cellular", "cellular fn1", "but never", "never in", "in plasma", "plasma fn1.", "fn1. a", "a variable", "region exists", "exists between", "between the", "the 14th", "14th and", "and 15th", "15th type", "iii module.", "module. this", "this contains", "contains the", "the binding", "binding site", "site for", "for alpha4", "alpha4 beta1", "beta1 and", "and alpha4beta7", "alpha4beta7 integrins.", "integrins. it", "it is", "is present", "in most", "most cellular", "occasionally in", "fn1. the", "the modules", "modules are", "are arranged", "arranged into", "into several", "several functional", "functional and", "and protein", "protein binding", "binding domains.", "domains. there", "there are", "are four", "four fn1", "fn1 binding", "binding domains", "one of", "of these", "these domains", "i1 5", "referred to", "to as", "as the", "the 'assembly", "'assembly domain'", "is required", "required for", "for the", "the initiation", "initiation of", "of fn1", "fn1 matrix", "matrix assembly.", "assembly. modules", "modules iii9", "iii9 10", "10 correspond", "correspond to", "to the", "the 'cell", "'cell binding", "binding domain'", "domain' of", "of fn1.", "the arg", "arg gly", "gly asp", "integrin binding", "binding sequence", "sequence located", "located in", "in iii10", "iii10 is", "is the", "the primary", "primary site", "site of", "fn1 to", "to cell", "cell attachment", "mediated predominantly", "predominantly by", "by alpha5", "alpha5 beta1", "and alphav", "alphav beta3", "beta3 integrins.", "integrins. the", "the 'synergy", "'synergy site'", "site' in", "in iii9", "iii9 modulates", "modulates fn1's", "fn1's association", "association with", "with alpha5", "beta1 integrins.", "fn1 also", "also contains", "contains interaction", "interaction domains", "domains for", "for fibrin", "i10 12", "i6 9", "ii1 2", "fibulin 1", "iii13 14", "iii12 14", "and fibrillin", "fibrillin 1", "& schwartzbauer", "schwartzbauer 2005", "sabatier et", "al. 2009", "2009 .

              ", ".

              fn1", "fn1 dimer", "dimer binding", "binding to", "to alpha5beta1", "alpha5beta1 integrin", "integrin stimulates", "stimulates self", "self association.", "association. binding", "binding is", "is thought", "thought to", "to lead", "lead to", "to a", "a conformational", "conformational change", "change in", "in fn1", "fn1 that", "that triggers", "triggers the", "the addition", "addition of", "of further", "further fn1", "fn1 dimers", ". i1", "5 functions", "functions as", "a unit", "unit that", "that is", "primary fn1", "matrix assembly", "assembly domain", "sottile et", "al. 1991", "but other", "other units", "units are", "are likely", "likely to", "to be", "be involved", "the process", "process is", "is not", "not fully", "fully understood.

              several", "understood.

              several ecm", "ecm proteins", "proteins appear", "appear to", "to require", "require the", "matrix for", "for their", "their own", "own assembly.", "assembly. fibrillin", "1 containing", "containing microfibrils", "microfibrils are", "are formed", "formed when", "when fibrillin", "1 multimers", "multimers bind", "bind to", "2009 .", "fn1 polymerization", "polymerization promotes", "promotes the", "the deposition", "deposition of", "of type", "type i", "and type", "iii collagen", "sottile and", "and hocking", "hocking 2002", "velling et", "al. 2002", ". inhibition", "inhibition of", "polymerization increases", "increases its", "its turnover", "turnover and", "and a", "a concomitant", "concomitant loss", "loss of", "of collagen", "collagen types", "types i", "and iii", "iii from", "from the", "the ecm", "al. 2007", "2007 .", "fn1 is", "is regulated", "regulated by", "by matrix", "matrix metalloproteinases", "particularly mmp14", "shi &", "& sottile", "sottile 2011", "2011 .", "fibronectin fn1", "is found in", "found in the", "in the extracellular", "the extracellular matrix", "matrix ecm", "ecm of", "of all cells", "all cells as", "cells as linear", "as linear and", "linear and branched", "and branched networks", "branched networks that", "networks that surround", "that surround and", "surround and connect", "and connect neighbouring", "connect neighbouring cells", "cells singh", "singh et al.", "et al. 2010", "al. 2010 .", "2010 . prior", ". prior to", "prior to matrix", "to matrix formation", "matrix formation fn1", "formation fn1 exists", "fn1 exists as", "exists as a", "as a protein", "a protein dimer.", "protein dimer. often", "dimer. often the", "often the two", "the two peptide", "two peptide chains", "peptide chains represent", "chains represent differentially", "represent differentially spliced", "differentially spliced variants.", "spliced variants. the", "variants. the chains", "the chains are", "chains are linked", "are linked by", "linked by a", "by a pair", "a pair of", "pair of c", "of c terminal", "c terminal disulfide", "terminal disulfide bonds", "disulfide bonds which", "bonds which are", "which are essential", "are essential for", "essential for subsequent", "for subsequent multimerization", "multimerization schwarzbaur", "schwarzbaur 1991 .", "1991 . fn1", ". fn1 monomers", "fn1 monomers have", "monomers have a", "have a molecular", "a molecular weight", "molecular weight of", "weight of 230", "of 230 270", "230 270 kda", "270 kda depending", "kda depending on", "depending on alternative", "on alternative splicing", "alternative splicing and", "splicing and contain", "and contain three", "contain three types", "three types of", "types of repeating", "of repeating unit", "unit i", "i ii", "ii and", "and iii. i", "iii. i and", "i and ii", "and ii are", "ii are stabilized", "are stabilized by", "stabilized by intra", "by intra chain", "intra chain disulfide", "chain disulfide bonds.", "disulfide bonds. the", "bonds. the absence", "the absence of", "absence of disulfide", "of disulfide bonds", "disulfide bonds in", "bonds in type", "in type iii", "type iii modules", "iii modules allows", "modules allows them", "allows them to", "them to partially", "to partially unfold", "partially unfold under", "unfold under applied", "under applied force", "force erickson", "erickson 2002 .", "2002 . three", ". three regions", "three regions of", "regions of variable", "of variable splicing", "variable splicing occur", "splicing occur along", "occur along the", "along the length", "the length of", "length of the", "of the fn1", "the fn1 monomer", "monomer mao", "mao & schwarzbauer", "& schwarzbauer 2005", "schwarzbauer 2005 .", "2005 . one", ". one or", "one or both", "or both of", "both of the", "of the 'extra'", "the 'extra' type", "'extra' type iii", "iii modules eiiia", "modules eiiia and", "eiiia and eiiib", "and eiiib may", "eiiib may be", "may be present", "be present in", "present in cellular", "in cellular fn1", "fn1 but", "but never in", "never in plasma", "in plasma fn1.", "plasma fn1. a", "fn1. a variable", "variable v", "v region", "region exists between", "exists between the", "between the 14th", "the 14th and", "14th and 15th", "and 15th type", "15th type iii", "type iii module.", "iii module. this", "module. this contains", "this contains the", "contains the binding", "the binding site", "binding site for", "site for alpha4", "for alpha4 beta1", "alpha4 beta1 and", "beta1 and alpha4beta7", "and alpha4beta7 integrins.", "alpha4beta7 integrins. it", "integrins. it is", "it is present", "is present in", "present in most", "in most cellular", "most cellular fn1", "fn1 occasionally", "occasionally in plasma", "plasma fn1. the", "fn1. the modules", "the modules are", "modules are arranged", "are arranged into", "arranged into several", "into several functional", "several functional and", "functional and protein", "and protein binding", "protein binding domains.", "binding domains. there", "domains. there are", "there are four", "are four fn1", "four fn1 binding", "fn1 binding domains", "domains mao", ". one of", "one of these", "of these domains", "domains i1", "referred to as", "to as the", "as the 'assembly", "the 'assembly domain'", "domain' is", "is required for", "required for the", "for the initiation", "the initiation of", "initiation of fn1", "of fn1 matrix", "fn1 matrix assembly.", "matrix assembly. modules", "assembly. modules iii9", "modules iii9 10", "iii9 10 correspond", "10 correspond to", "correspond to the", "to the 'cell", "the 'cell binding", "'cell binding domain'", "binding domain' of", "domain' of fn1.", "of fn1. the", "fn1. the arg", "the arg gly", "arg gly asp", "asp rgd", "rgd integrin", "integrin binding sequence", "binding sequence located", "sequence located in", "located in iii10", "in iii10 is", "iii10 is the", "is the primary", "the primary site", "primary site of", "site of fn1", "of fn1 to", "fn1 to cell", "to cell attachment", "attachment mediated", "mediated predominantly by", "predominantly by alpha5", "by alpha5 beta1", "alpha5 beta1 and", "beta1 and alphav", "and alphav beta3", "alphav beta3 integrins.", "beta3 integrins. the", "integrins. the 'synergy", "the 'synergy site'", "'synergy site' in", "site' in iii9", "in iii9 modulates", "iii9 modulates fn1's", "modulates fn1's association", "fn1's association with", "association with alpha5", "with alpha5 beta1", "alpha5 beta1 integrins.", "integrins. fn1", "fn1 also contains", "also contains interaction", "contains interaction domains", "interaction domains for", "domains for fibrin", "fibrin i1", "5 i10", "collagen i6", "9 ii1", "1 iii13", "heparin syndecan", "syndecan iii12", "14 and", "and fibrillin 1", "1 i6", "mao & schwartzbauer", "& schwartzbauer 2005", "2005 sabatier", "sabatier et al.", "et al. 2009", "al. 2009 .

              ", "2009 .

              fn1", ".

              fn1 dimer", "fn1 dimer binding", "dimer binding to", "binding to alpha5beta1", "to alpha5beta1 integrin", "alpha5beta1 integrin stimulates", "integrin stimulates self", "stimulates self association.", "self association. binding", "association. binding is", "binding is thought", "is thought to", "thought to lead", "to lead to", "lead to a", "to a conformational", "a conformational change", "conformational change in", "change in fn1", "in fn1 that", "fn1 that triggers", "that triggers the", "triggers the addition", "the addition of", "addition of further", "of further fn1", "further fn1 dimers", "dimers singh", "2010 . i1", ". i1 5", "i1 5 functions", "5 functions as", "functions as a", "as a unit", "a unit that", "unit that is", "that is the", "the primary fn1", "primary fn1 matrix", "fn1 matrix assembly", "matrix assembly domain", "domain sottile", "sottile et al.", "et al. 1991", "1991 but", "but other units", "other units are", "units are likely", "are likely to", "likely to be", "to be involved", "involved singh", "the process is", "process is not", "is not fully", "not fully understood.

              several", "fully understood.

              several ecm", "understood.

              several ecm proteins", "ecm proteins appear", "proteins appear to", "appear to require", "to require the", "require the fn1", "the fn1 matrix", "fn1 matrix for", "matrix for their", "for their own", "their own assembly.", "own assembly. fibrillin", "assembly. fibrillin 1", "fibrillin 1 containing", "1 containing microfibrils", "containing microfibrils are", "microfibrils are formed", "are formed when", "formed when fibrillin", "when fibrillin 1", "fibrillin 1 multimers", "1 multimers bind", "multimers bind to", "bind to the", "to the fn1", "matrix sabatier", "al. 2009 .", "2009 . fn1", ". fn1 polymerization", "fn1 polymerization promotes", "polymerization promotes the", "promotes the deposition", "the deposition of", "deposition of type", "of type i", "type i and", "i and type", "and type iii", "type iii collagen", "collagen sottile", "sottile and hocking", "and hocking 2002", "2002 velling", "velling et al.", "et al. 2002", "al. 2002 .", "2002 . inhibition", ". inhibition of", "inhibition of fn1", "of fn1 polymerization", "fn1 polymerization increases", "polymerization increases its", "increases its turnover", "its turnover and", "turnover and a", "and a concomitant", "a concomitant loss", "concomitant loss of", "loss of collagen", "of collagen types", "collagen types i", "types i and", "i and iii", "and iii from", "iii from the", "from the ecm", "ecm sottile", "2002 sottile", "et al. 2007", "al. 2007 .", "2007 . fn1", ". fn1 is", "fn1 is regulated", "is regulated by", "regulated by matrix", "by matrix metalloproteinases", "metalloproteinases particularly", "mmp14 shi", "shi & sottile", "& sottile 2011", "sottile 2011 .", "fn1 is found", "is found in the", "found in the extracellular", "in the extracellular matrix", "extracellular matrix ecm", "ecm of all", "of all cells as", "all cells as linear", "cells as linear and", "as linear and branched", "linear and branched networks", "and branched networks that", "branched networks that surround", "networks that surround and", "that surround and connect", "surround and connect neighbouring", "and connect neighbouring cells", "neighbouring cells singh", "cells singh et", "singh et al. 2010", "et al. 2010 .", "al. 2010 . prior", "2010 . prior to", ". prior to matrix", "prior to matrix formation", "to matrix formation fn1", "matrix formation fn1 exists", "formation fn1 exists as", "fn1 exists as a", "exists as a protein", "as a protein dimer.", "a protein dimer. often", "protein dimer. often the", "dimer. often the two", "often the two peptide", "the two peptide chains", "two peptide chains represent", "peptide chains represent differentially", "chains represent differentially spliced", "represent differentially spliced variants.", "differentially spliced variants. the", "spliced variants. the chains", "variants. the chains are", "the chains are linked", "chains are linked by", "are linked by a", "linked by a pair", "by a pair of", "a pair of c", "pair of c terminal", "of c terminal disulfide", "c terminal disulfide bonds", "terminal disulfide bonds which", "disulfide bonds which are", "bonds which are essential", "which are essential for", "are essential for subsequent", "essential for subsequent multimerization", "subsequent multimerization schwarzbaur", "multimerization schwarzbaur 1991", "schwarzbaur 1991 . fn1", "1991 . fn1 monomers", ". fn1 monomers have", "fn1 monomers have a", "monomers have a molecular", "have a molecular weight", "a molecular weight of", "molecular weight of 230", "weight of 230 270", "of 230 270 kda", "230 270 kda depending", "270 kda depending on", "kda depending on alternative", "depending on alternative splicing", "on alternative splicing and", "alternative splicing and contain", "splicing and contain three", "and contain three types", "contain three types of", "three types of repeating", "types of repeating unit", "repeating unit i", "ii and iii.", "and iii. i and", "iii. i and ii", "i and ii are", "and ii are stabilized", "ii are stabilized by", "are stabilized by intra", "stabilized by intra chain", "by intra chain disulfide", "intra chain disulfide bonds.", "chain disulfide bonds. the", "disulfide bonds. the absence", "bonds. the absence of", "the absence of disulfide", "absence of disulfide bonds", "of disulfide bonds in", "disulfide bonds in type", "bonds in type iii", "in type iii modules", "type iii modules allows", "iii modules allows them", "modules allows them to", "allows them to partially", "them to partially unfold", "to partially unfold under", "partially unfold under applied", "unfold under applied force", "applied force erickson", "force erickson 2002", "erickson 2002 . three", "2002 . three regions", ". three regions of", "three regions of variable", "regions of variable splicing", "of variable splicing occur", "variable splicing occur along", "splicing occur along the", "occur along the length", "along the length of", "the length of the", "length of the fn1", "of the fn1 monomer", "fn1 monomer mao", "monomer mao &", "mao & schwarzbauer 2005", "& schwarzbauer 2005 .", "schwarzbauer 2005 . one", "2005 . one or", ". one or both", "one or both of", "or both of the", "both of the 'extra'", "of the 'extra' type", "the 'extra' type iii", "'extra' type iii modules", "type iii modules eiiia", "iii modules eiiia and", "modules eiiia and eiiib", "eiiia and eiiib may", "and eiiib may be", "eiiib may be present", "may be present in", "be present in cellular", "present in cellular fn1", "cellular fn1 but", "fn1 but never", "but never in plasma", "never in plasma fn1.", "in plasma fn1. a", "plasma fn1. a variable", "a variable v", "v region exists", "region exists between the", "exists between the 14th", "between the 14th and", "the 14th and 15th", "14th and 15th type", "and 15th type iii", "15th type iii module.", "type iii module. this", "iii module. this contains", "module. this contains the", "this contains the binding", "contains the binding site", "the binding site for", "binding site for alpha4", "site for alpha4 beta1", "for alpha4 beta1 and", "alpha4 beta1 and alpha4beta7", "beta1 and alpha4beta7 integrins.", "and alpha4beta7 integrins. it", "alpha4beta7 integrins. it is", "integrins. it is present", "it is present in", "is present in most", "present in most cellular", "in most cellular fn1", "cellular fn1 occasionally", "fn1 occasionally in", "occasionally in plasma fn1.", "in plasma fn1. the", "plasma fn1. the modules", "fn1. the modules are", "the modules are arranged", "modules are arranged into", "are arranged into several", "arranged into several functional", "into several functional and", "several functional and protein", "functional and protein binding", "and protein binding domains.", "protein binding domains. there", "binding domains. there are", "domains. there are four", "there are four fn1", "are four fn1 binding", "four fn1 binding domains", "binding domains mao", "domains mao &", "2005 . one of", ". one of these", "one of these domains", "these domains i1", "domains i1 5", "5 referred", "referred to as the", "to as the 'assembly", "as the 'assembly domain'", "'assembly domain' is", "domain' is required", "is required for the", "required for the initiation", "for the initiation of", "the initiation of fn1", "initiation of fn1 matrix", "of fn1 matrix assembly.", "fn1 matrix assembly. modules", "matrix assembly. modules iii9", "assembly. modules iii9 10", "modules iii9 10 correspond", "iii9 10 correspond to", "10 correspond to the", "correspond to the 'cell", "to the 'cell binding", "the 'cell binding domain'", "'cell binding domain' of", "binding domain' of fn1.", "domain' of fn1. the", "of fn1. the arg", "fn1. the arg gly", "the arg gly asp", "gly asp rgd", "rgd integrin binding", "integrin binding sequence located", "binding sequence located in", "sequence located in iii10", "located in iii10 is", "in iii10 is the", "iii10 is the primary", "is the primary site", "the primary site of", "primary site of fn1", "site of fn1 to", "of fn1 to cell", "fn1 to cell attachment", "cell attachment mediated", "attachment mediated predominantly", "mediated predominantly by alpha5", "predominantly by alpha5 beta1", "by alpha5 beta1 and", "alpha5 beta1 and alphav", "beta1 and alphav beta3", "and alphav beta3 integrins.", "alphav beta3 integrins. the", "beta3 integrins. the 'synergy", "integrins. the 'synergy site'", "the 'synergy site' in", "'synergy site' in iii9", "site' in iii9 modulates", "in iii9 modulates fn1's", "iii9 modulates fn1's association", "modulates fn1's association with", "fn1's association with alpha5", "association with alpha5 beta1", "with alpha5 beta1 integrins.", "beta1 integrins. fn1", "integrins. fn1 also", "fn1 also contains interaction", "also contains interaction domains", "contains interaction domains for", "interaction domains for fibrin", "for fibrin i1", "fibrin i1 5", "i1 5 i10", "5 i10 12", "12 collagen", "collagen i6 9", "i6 9 ii1", "9 ii1 2", "2 fibulin", "fibulin 1 iii13", "1 iii13 14", "14 heparin", "syndecan iii12 14", "iii12 14 and", "14 and fibrillin", "fibrillin 1 i6", "1 i6 9", "9 mao", "mao & schwartzbauer 2005", "schwartzbauer 2005 sabatier", "2005 sabatier et", "sabatier et al. 2009", "et al. 2009 .

              ", "al. 2009 .

              fn1", "2009 .

              fn1 dimer", ".

              fn1 dimer binding", "fn1 dimer binding to", "dimer binding to alpha5beta1", "binding to alpha5beta1 integrin", "to alpha5beta1 integrin stimulates", "alpha5beta1 integrin stimulates self", "integrin stimulates self association.", "stimulates self association. binding", "self association. binding is", "association. binding is thought", "binding is thought to", "is thought to lead", "thought to lead to", "to lead to a", "lead to a conformational", "to a conformational change", "a conformational change in", "conformational change in fn1", "change in fn1 that", "in fn1 that triggers", "fn1 that triggers the", "that triggers the addition", "triggers the addition of", "the addition of further", "addition of further fn1", "of further fn1 dimers", "fn1 dimers singh", "dimers singh et", "al. 2010 . i1", "2010 . i1 5", ". i1 5 functions", "i1 5 functions as", "5 functions as a", "functions as a unit", "as a unit that", "a unit that is", "unit that is the", "that is the primary", "is the primary fn1", "the primary fn1 matrix", "primary fn1 matrix assembly", "fn1 matrix assembly domain", "assembly domain sottile", "domain sottile et", "sottile et al. 1991", "al. 1991 but", "1991 but other", "but other units are", "other units are likely", "units are likely to", "are likely to be", "likely to be involved", "be involved singh", "involved singh et", "2010 the", "the process is not", "process is not fully", "is not fully understood.

              several", "not fully understood.

              several ecm", "fully understood.

              several ecm proteins", "understood.

              several ecm proteins appear", "ecm proteins appear to", "proteins appear to require", "appear to require the", "to require the fn1", "require the fn1 matrix", "the fn1 matrix for", "fn1 matrix for their", "matrix for their own", "for their own assembly.", "their own assembly. fibrillin", "own assembly. fibrillin 1", "assembly. fibrillin 1 containing", "fibrillin 1 containing microfibrils", "1 containing microfibrils are", "containing microfibrils are formed", "microfibrils are formed when", "are formed when fibrillin", "formed when fibrillin 1", "when fibrillin 1 multimers", "fibrillin 1 multimers bind", "1 multimers bind to", "multimers bind to the", "bind to the fn1", "to the fn1 matrix", "fn1 matrix sabatier", "matrix sabatier et", "et al. 2009 .", "al. 2009 . fn1", "2009 . fn1 polymerization", ". fn1 polymerization promotes", "fn1 polymerization promotes the", "polymerization promotes the deposition", "promotes the deposition of", "the deposition of type", "deposition of type i", "of type i and", "type i and type", "i and type iii", "and type iii collagen", "iii collagen sottile", "collagen sottile and", "sottile and hocking 2002", "hocking 2002 velling", "2002 velling et", "velling et al. 2002", "et al. 2002 .", "al. 2002 . inhibition", "2002 . inhibition of", ". inhibition of fn1", "inhibition of fn1 polymerization", "of fn1 polymerization increases", "fn1 polymerization increases its", "polymerization increases its turnover", "increases its turnover and", "its turnover and a", "turnover and a concomitant", "and a concomitant loss", "a concomitant loss of", "concomitant loss of collagen", "loss of collagen types", "of collagen types i", "collagen types i and", "types i and iii", "i and iii from", "and iii from the", "iii from the ecm", "the ecm sottile", "ecm sottile and", "hocking 2002 sottile", "2002 sottile et", "sottile et al. 2007", "et al. 2007 .", "al. 2007 . fn1", "2007 . fn1 is", ". fn1 is regulated", "fn1 is regulated by", "is regulated by matrix", "regulated by matrix metalloproteinases", "matrix metalloproteinases particularly", "metalloproteinases particularly mmp14", "particularly mmp14 shi", "mmp14 shi &", "shi & sottile 2011", "& sottile 2011 .", "fibronectin fn1 is", "fn1 is found in", "is found in the extracellular", "found in the extracellular matrix", "the extracellular matrix ecm", "matrix ecm of", "ecm of all cells", "of all cells as linear", "all cells as linear and", "cells as linear and branched", "as linear and branched networks", "linear and branched networks that", "and branched networks that surround", "branched networks that surround and", "networks that surround and connect", "that surround and connect neighbouring", "surround and connect neighbouring cells", "connect neighbouring cells singh", "neighbouring cells singh et", "cells singh et al.", "singh et al. 2010 .", "et al. 2010 . prior", "al. 2010 . prior to", "2010 . prior to matrix", ". prior to matrix formation", "prior to matrix formation fn1", "to matrix formation fn1 exists", "matrix formation fn1 exists as", "formation fn1 exists as a", "fn1 exists as a protein", "exists as a protein dimer.", "as a protein dimer. often", "a protein dimer. often the", "protein dimer. often the two", "dimer. often the two peptide", "often the two peptide chains", "the two peptide chains represent", "two peptide chains represent differentially", "peptide chains represent differentially spliced", "chains represent differentially spliced variants.", "represent differentially spliced variants. the", "differentially spliced variants. the chains", "spliced variants. the chains are", "variants. the chains are linked", "the chains are linked by", "chains are linked by a", "are linked by a pair", "linked by a pair of", "by a pair of c", "a pair of c terminal", "pair of c terminal disulfide", "of c terminal disulfide bonds", "c terminal disulfide bonds which", "terminal disulfide bonds which are", "disulfide bonds which are essential", "bonds which are essential for", "which are essential for subsequent", "are essential for subsequent multimerization", "for subsequent multimerization schwarzbaur", "subsequent multimerization schwarzbaur 1991", "multimerization schwarzbaur 1991 .", "schwarzbaur 1991 . fn1 monomers", "1991 . fn1 monomers have", ". fn1 monomers have a", "fn1 monomers have a molecular", "monomers have a molecular weight", "have a molecular weight of", "a molecular weight of 230", "molecular weight of 230 270", "weight of 230 270 kda", "of 230 270 kda depending", "230 270 kda depending on", "270 kda depending on alternative", "kda depending on alternative splicing", "depending on alternative splicing and", "on alternative splicing and contain", "alternative splicing and contain three", "splicing and contain three types", "and contain three types of", "contain three types of repeating", "three types of repeating unit", "of repeating unit i", "unit i ii", "i ii and", "ii and iii. i", "and iii. i and ii", "iii. i and ii are", "i and ii are stabilized", "and ii are stabilized by", "ii are stabilized by intra", "are stabilized by intra chain", "stabilized by intra chain disulfide", "by intra chain disulfide bonds.", "intra chain disulfide bonds. the", "chain disulfide bonds. the absence", "disulfide bonds. the absence of", "bonds. the absence of disulfide", "the absence of disulfide bonds", "absence of disulfide bonds in", "of disulfide bonds in type", "disulfide bonds in type iii", "bonds in type iii modules", "in type iii modules allows", "type iii modules allows them", "iii modules allows them to", "modules allows them to partially", "allows them to partially unfold", "them to partially unfold under", "to partially unfold under applied", "partially unfold under applied force", "under applied force erickson", "applied force erickson 2002", "force erickson 2002 .", "erickson 2002 . three regions", "2002 . three regions of", ". three regions of variable", "three regions of variable splicing", "regions of variable splicing occur", "of variable splicing occur along", "variable splicing occur along the", "splicing occur along the length", "occur along the length of", "along the length of the", "the length of the fn1", "length of the fn1 monomer", "the fn1 monomer mao", "fn1 monomer mao &", "monomer mao & schwarzbauer", "mao & schwarzbauer 2005 .", "& schwarzbauer 2005 . one", "schwarzbauer 2005 . one or", "2005 . one or both", ". one or both of", "one or both of the", "or both of the 'extra'", "both of the 'extra' type", "of the 'extra' type iii", "the 'extra' type iii modules", "'extra' type iii modules eiiia", "type iii modules eiiia and", "iii modules eiiia and eiiib", "modules eiiia and eiiib may", "eiiia and eiiib may be", "and eiiib may be present", "eiiib may be present in", "may be present in cellular", "be present in cellular fn1", "in cellular fn1 but", "cellular fn1 but never", "fn1 but never in", "but never in plasma fn1.", "never in plasma fn1. a", "in plasma fn1. a variable", "fn1. a variable v", "variable v region", "v region exists between", "region exists between the 14th", "exists between the 14th and", "between the 14th and 15th", "the 14th and 15th type", "14th and 15th type iii", "and 15th type iii module.", "15th type iii module. this", "type iii module. this contains", "iii module. this contains the", "module. this contains the binding", "this contains the binding site", "contains the binding site for", "the binding site for alpha4", "binding site for alpha4 beta1", "site for alpha4 beta1 and", "for alpha4 beta1 and alpha4beta7", "alpha4 beta1 and alpha4beta7 integrins.", "beta1 and alpha4beta7 integrins. it", "and alpha4beta7 integrins. it is", "alpha4beta7 integrins. it is present", "integrins. it is present in", "it is present in most", "is present in most cellular", "present in most cellular fn1", "most cellular fn1 occasionally", "cellular fn1 occasionally in", "fn1 occasionally in plasma", "occasionally in plasma fn1. the", "in plasma fn1. the modules", "plasma fn1. the modules are", "fn1. the modules are arranged", "the modules are arranged into", "modules are arranged into several", "are arranged into several functional", "arranged into several functional and", "into several functional and protein", "several functional and protein binding", "functional and protein binding domains.", "and protein binding domains. there", "protein binding domains. there are", "binding domains. there are four", "domains. there are four fn1", "there are four fn1 binding", "are four fn1 binding domains", "fn1 binding domains mao", "binding domains mao &", "domains mao & schwarzbauer", "schwarzbauer 2005 . one of", "2005 . one of these", ". one of these domains", "of these domains i1", "these domains i1 5", "i1 5 referred", "5 referred to", "referred to as the 'assembly", "to as the 'assembly domain'", "the 'assembly domain' is", "'assembly domain' is required", "domain' is required for", "is required for the initiation", "required for the initiation of", "for the initiation of fn1", "the initiation of fn1 matrix", "initiation of fn1 matrix assembly.", "of fn1 matrix assembly. modules", "fn1 matrix assembly. modules iii9", "matrix assembly. modules iii9 10", "assembly. modules iii9 10 correspond", "modules iii9 10 correspond to", "iii9 10 correspond to the", "10 correspond to the 'cell", "correspond to the 'cell binding", "to the 'cell binding domain'", "the 'cell binding domain' of", "'cell binding domain' of fn1.", "binding domain' of fn1. the", "domain' of fn1. the arg", "of fn1. the arg gly", "fn1. the arg gly asp", "arg gly asp rgd", "asp rgd integrin", "rgd integrin binding sequence", "integrin binding sequence located in", "binding sequence located in iii10", "sequence located in iii10 is", "located in iii10 is the", "in iii10 is the primary", "iii10 is the primary site", "is the primary site of", "the primary site of fn1", "primary site of fn1 to", "site of fn1 to cell", "of fn1 to cell attachment", "to cell attachment mediated", "cell attachment mediated predominantly", "attachment mediated predominantly by", "mediated predominantly by alpha5 beta1", "predominantly by alpha5 beta1 and", "by alpha5 beta1 and alphav", "alpha5 beta1 and alphav beta3", "beta1 and alphav beta3 integrins.", "and alphav beta3 integrins. the", "alphav beta3 integrins. the 'synergy", "beta3 integrins. the 'synergy site'", "integrins. the 'synergy site' in", "the 'synergy site' in iii9", "'synergy site' in iii9 modulates", "site' in iii9 modulates fn1's", "in iii9 modulates fn1's association", "iii9 modulates fn1's association with", "modulates fn1's association with alpha5", "fn1's association with alpha5 beta1", "association with alpha5 beta1 integrins.", "alpha5 beta1 integrins. fn1", "beta1 integrins. fn1 also", "integrins. fn1 also contains", "fn1 also contains interaction domains", "also contains interaction domains for", "contains interaction domains for fibrin", "domains for fibrin i1", "for fibrin i1 5", "i1 5 i10 12", "i10 12 collagen", "i6 9 ii1 2", "ii1 2 fibulin", "2 fibulin 1", "fibulin 1 iii13 14", "iii13 14 heparin", "heparin syndecan iii12", "iii12 14 and fibrillin", "14 and fibrillin 1", "and fibrillin 1 i6", "fibrillin 1 i6 9", "i6 9 mao", "9 mao &", "& schwartzbauer 2005 sabatier", "schwartzbauer 2005 sabatier et", "2005 sabatier et al.", "sabatier et al. 2009 .

              ", "et al. 2009 .

              fn1", "al. 2009 .

              fn1 dimer", "2009 .

              fn1 dimer binding", ".

              fn1 dimer binding to", "fn1 dimer binding to alpha5beta1", "dimer binding to alpha5beta1 integrin", "binding to alpha5beta1 integrin stimulates", "to alpha5beta1 integrin stimulates self", "alpha5beta1 integrin stimulates self association.", "integrin stimulates self association. binding", "stimulates self association. binding is", "self association. binding is thought", "association. binding is thought to", "binding is thought to lead", "is thought to lead to", "thought to lead to a", "to lead to a conformational", "lead to a conformational change", "to a conformational change in", "a conformational change in fn1", "conformational change in fn1 that", "change in fn1 that triggers", "in fn1 that triggers the", "fn1 that triggers the addition", "that triggers the addition of", "triggers the addition of further", "the addition of further fn1", "addition of further fn1 dimers", "further fn1 dimers singh", "fn1 dimers singh et", "dimers singh et al.", "et al. 2010 . i1", "al. 2010 . i1 5", "2010 . i1 5 functions", ". i1 5 functions as", "i1 5 functions as a", "5 functions as a unit", "functions as a unit that", "as a unit that is", "a unit that is the", "unit that is the primary", "that is the primary fn1", "is the primary fn1 matrix", "the primary fn1 matrix assembly", "primary fn1 matrix assembly domain", "matrix assembly domain sottile", "assembly domain sottile et", "domain sottile et al.", "et al. 1991 but", "al. 1991 but other", "1991 but other units", "but other units are likely", "other units are likely to", "units are likely to be", "are likely to be involved", "to be involved singh", "be involved singh et", "involved singh et al.", "al. 2010 the", "2010 the process", "the process is not fully", "process is not fully understood.

              several", "is not fully understood.

              several ecm", "not fully understood.

              several ecm proteins", "fully understood.

              several ecm proteins appear", "understood.

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between the", "peptide bond between the incoming", "bond between the incoming amino", "between the incoming amino acid", "the incoming amino acid and", "incoming amino acid and the", "amino acid and the peptide", "acid and the peptide found", "and the peptide found in", "the peptide found in the", "peptide found in the peptidyl", "found in the peptidyl trna", "in the peptidyl trna binding", "the peptidyl trna binding site", "trna binding site p", "binding site p site", "site p site .", "p site . d: in", "site . d: in the", ". d: in the pre", "d: in the pre translocation", "in the pre translocation state", "the pre translocation state of", "pre translocation state of the", "translocation state of the ribosome", "of the ribosome the", "the ribosome the eef2:gtp", "ribosome the eef2:gtp enters", "the eef2:gtp enters the ribosome", "enters the ribosome physically", "the ribosome physically translocating", "ribosome physically translocating the", "physically translocating the peptidyl trna", "translocating the peptidyl trna out", "the peptidyl trna out of", "peptidyl trna out of the", "trna out of the a", "out of the a site", "of the a site to", "the a site to p", "a site to p site", "site to p site and", "to p site and leaves", "p site and leaves the", "site and leaves the ribosome", "and leaves the ribosome eef2:gdp.", "leaves the ribosome eef2:gdp. this", "the ribosome eef2:gdp. this action", "ribosome eef2:gdp. this action of", "eef2:gdp. this action of eef2:gtp", "this action of eef2:gtp accounts", "action of eef2:gtp accounts for", "of eef2:gtp accounts for the", "eef2:gtp accounts for the precise", "accounts for the precise movement", "for the precise movement of", "the precise movement of the", "precise movement of the mrna", "movement of the mrna by", "of the mrna by 3", "the mrna by 3 nucleotides.consequently", "by 3 nucleotides.consequently deacylated", "3 nucleotides.consequently deacylated trna", "nucleotides.consequently deacylated trna is", 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the", "the reverse transcription", "transcription complex is", "complex is thus", "is thus liberated", "thus liberated from", "liberated from the", "from the plasma", "the plasma membrane.", "plasma membrane. it", "membrane. it is", "it is believed", "is believed that", "believed that the", "that the transiting", "the transiting viral", "transiting viral nucleoprotein", "viral nucleoprotein complex", "nucleoprotein complex associates", "complex associates with", "associates with the", "with the elements", "the elements of", "elements of cytoskeleton", "of cytoskeleton like", "cytoskeleton like actin", "like actin microfilaments.", "hiv 1 uncoating is", "1 uncoating is a", "uncoating is a poorly", "is a poorly understood", "a poorly understood process.", "poorly understood process. it", "understood process. it likely", "process. it likely involves", "it likely involves a", "likely involves a progressive", "involves a progressive and", "a progressive and partial", "progressive and partial dissembly", "and partial dissembly of", "partial dissembly of matrix", "dissembly of matrix and", "of matrix and capsid", "matrix and capsid layers.", "capsid layers. while", "layers. while viral", "while viral proteins like", "viral proteins like ma", "proteins like ma and", "like ma and nef", "ma and nef are", "and nef are thought", "nef are thought to", "are thought to be", "thought to be involved", "be involved the", "involved the primary", "the primary cause seems", "primary cause seems to", "cause seems to be", "seems to be the", "to be the cytosolic", "be the cytosolic ph", "the cytosolic ph and", "cytosolic ph and a", "ph and a simple", "and a simple dilution", "a simple dilution effect.", "simple dilution effect. successful", "dilution effect. successful uncoating", "effect. successful uncoating generates", "successful uncoating generates the", "uncoating generates the viral", "generates the viral reverse", "the viral reverse transcription", "viral reverse transcription complex", "transcription complex which", "complex which comprises", "which comprises the diploid", "comprises the diploid viral", "the diploid viral rna", "diploid viral rna genome", "rna genome trnalys", "genome trnalys primer", "trnalys primer rt", "nc viral", "protein r vpr", "vpr and various", "and various host proteins", "host proteins the", "proteins the reverse", "the reverse transcription complex", "reverse transcription complex is", "transcription complex is thus", "complex is thus liberated", "is thus liberated from", "thus liberated from the", "liberated from the plasma", "from the plasma membrane.", "the plasma membrane. it", "plasma membrane. it is", "membrane. it is believed", "it is believed that", "is believed that the", "believed that the transiting", "that the transiting viral", "the transiting viral nucleoprotein", "transiting viral nucleoprotein complex", "viral nucleoprotein complex associates", "nucleoprotein complex associates with", "complex associates with the", "associates with the elements", "with the elements of", "the elements of cytoskeleton", "elements of cytoskeleton like", "of cytoskeleton like actin", "cytoskeleton like actin microfilaments.", "hiv 1 uncoating is a", "1 uncoating is a poorly", "uncoating is a poorly understood", "is a poorly understood process.", "a poorly understood process. it", "poorly understood process. it likely", "understood process. it likely involves", "process. it likely involves a", "it likely involves a progressive", "likely involves a progressive and", "involves a progressive and partial", "a progressive and partial dissembly", "progressive and partial dissembly of", "and partial dissembly of matrix", "partial dissembly of matrix and", "dissembly of matrix and capsid", "of matrix and capsid layers.", "and capsid layers. while", "capsid layers. while viral", "layers. while viral proteins", "while viral proteins like ma", "viral proteins like ma and", "proteins like ma and nef", "like ma and nef are", "ma and nef are thought", "and nef are thought to", "nef are thought to be", "are thought to be involved", "to be involved the", "be involved the primary", "involved the primary cause", "the primary cause seems to", "primary cause seems to be", "cause seems to be the", "seems to be the cytosolic", "to be the cytosolic ph", "be the cytosolic ph and", "the cytosolic ph and a", "cytosolic ph and a simple", "ph and a simple dilution", "and a simple dilution effect.", "a simple dilution effect. successful", "simple dilution effect. successful uncoating", "dilution effect. successful uncoating generates", "effect. successful uncoating generates the", "successful uncoating generates the viral", "uncoating generates the viral reverse", "generates the viral reverse transcription", "the viral reverse transcription complex", "reverse transcription complex which", "transcription complex which comprises", "complex which comprises the", "which comprises the diploid viral", "comprises the diploid viral rna", "the diploid viral rna genome", "viral rna genome trnalys", "rna genome trnalys primer", "primer rt in", "rt in ma", "in ma nucleocapsid", "ma nucleocapsid nc", "nc viral protein", "viral protein r vpr", "r vpr and", "vpr and various host", "various host proteins the", "host proteins the reverse", "proteins the reverse transcription", "the reverse transcription complex is", "reverse transcription complex is thus", "transcription complex is thus liberated", "complex is thus liberated from", "is thus liberated from the", "thus liberated from the plasma", "liberated from the plasma membrane.", "from the plasma membrane. it", "the plasma membrane. it is", "plasma membrane. it is believed", "membrane. it is believed that", "it is believed that the", "is believed that the transiting", "believed that the transiting viral", "that the transiting viral nucleoprotein", "the transiting viral nucleoprotein complex", "transiting viral nucleoprotein complex associates", "viral nucleoprotein complex associates with", "nucleoprotein complex associates with the", "complex associates with the elements", "associates with the elements of", "with the elements of cytoskeleton", "the elements of cytoskeleton like", "elements of cytoskeleton like actin", "of cytoskeleton like actin microfilaments." ] }, { "record_id": "GLY_000594_1_1262", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162589", "r hsa", "hsa 162589", "r hsa 162589" ] }, { "record_id": "GLY_000594_1_1262", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "reverse transcription", "transcription of", "of hiv", "hiv rna", "reverse transcription of", "transcription of hiv", "of hiv rna", "reverse transcription of hiv", "transcription of hiv rna", "reverse transcription of hiv rna", "the rna", "rna genome", "genome of", "hiv 1", "like that", "that of", "of other", "other retroviruses", "is reverse", "reverse transcribed", "baltimore 1970", "temin and", "and mizutani", "mizutani 1970", "into double", "double stranded", "stranded dna", "which is", "is then", "then integrated", "integrated into", "into a", "a host", "host cell", "cell chromosome", "chromosome and", "and transcribed", "transcribed to", "to yield", "yield both", "both viral", "viral mrnas", "mrnas and", "and viral", "viral genomic", "genomic rnas.", "rnas. hiv", "1 reverse", "transcription takes", "takes place", "place in", "in the", "the cytosol", "cytosol of", "of a", "a newly", "newly infected", "infected host", "cell and", "and involves", "involves multiple", "multiple steps", "steps of", "of rna", "rna synthesis", "synthesis and", "and degradation", "degradation of", "of the", "rna strand", "strand of", "of rna:dna", "rna:dna duplexes", "duplexes mediated", "mediated by", "by the", "the hiv", "1 rt", "rt protein", "as well", "well as", "as two", "two template", "template switches", "yield a", "a dna", "dna duplex", "duplex colinear", "colinear with", "with the", "the viral", "genomic rna", "rna but", "but with", "with additional", "additional long", "long terminal", "terminal repeat", "sequence motifs", "motifs at", "at both", "both ends", "telesnitsky and", "and goff", "goff 1997", "jonckheere et", "et al.", "al. 2000", "2000 .

              hiv", ".

              hiv 1", "rt has", "has two", "two catalytic", "catalytic activities", "activities essential", "essential for", "for transcription", "duplex copy", "copy of", "genomic rna:", "rna: a", "a reverse", "reverse transcriptase", "transcriptase activity", "activity and", "and an", "an rnase", "rnase h", "h activity.", "activity. the", "the reverse", "transcriptase is", "is primer", "primer dependent", "dependent and", "and can", "can transcribe", "transcribe both", "both rna", "rna and", "and dna", "dna templates", "templates in", "in a", "a 5'", "5' 3'", "3' direction.", "direction. the", "the rnaseh", "rnaseh acts", "acts on", "on the", "duplexes and", "can catalyze", "catalyze both", "both endo", "and exonucleolytic", "exonucleolytic cleavage", "cleavage of", "of such", "such an", "an rna", "rna strand.", "strand. rt", "rt is", "is a", "a heterodimer", "heterodimer of", "of 66", "66 and", "and 51", "51 kd", "kd polypeptides", "both generated", "generated by", "by cleavage", "1 pol", "pol gene", "gene product:", "product: p66", "p66 contains", "contains pol", "pol amino", "amino acid", "acid residues", "residues 599", "599 1158", "p51 contains", "contains residues", "599 1038.", "1038. both", "both active", "active sites", "sites of", "rt enzyme", "enzyme are", "are contained", "contained in", "the p66", "p66 polypeptide", "the polymerase", "polymerase activity", "activity in", "in its", "its aminoterminal", "aminoterminal region", "and the", "the rnase", "rnase in", "its carboxyterminus.", "carboxyterminus. the", "the p51", "p51 subunit", "subunit lacks", "lacks an", "an rnaseh", "rnaseh domain", "and while", "while its", "its polymerase", "polymerase domain", "domain is", "is intact", "its conformation", "conformation in", "the p66:p51", "p66:p51 heterodimer", "heterodimer occludes", "occludes the", "the active", "active site", "hughes et", "al. 1996", "jacobo molina", "molina et", "al. 1993", "kohlstaedt et", "al. 1992", "wang et", "al. 1994", "1994 .

              the", ".

              the process", "process of", "of reverse", "transcription is", "is outlined", "outlined in", "the figure", "figure below:", "below: viral", "and primer", "primer trna", "trna are", "are shown", "shown in", "in black", "\\minus\\ strand", "strand dna", "dna is", "is shown", "in red", "and \\plus\\", "\\plus\\ strand", "in blue.", "the rna genome", "rna genome of", "genome of hiv", "of hiv 1", "1 like", "like that of", "that of other", "of other retroviruses", "retroviruses is", "is reverse transcribed", "transcribed baltimore", "1970 temin", "temin and mizutani", "and mizutani 1970", "1970 into", "into double stranded", "double stranded dna", "dna which", "which is then", "is then integrated", "then integrated into", "integrated into a", "into a host", "a host cell", "host cell chromosome", "cell chromosome and", "chromosome and transcribed", "and transcribed to", "transcribed to yield", "to yield both", "yield both viral", "both viral mrnas", "viral mrnas and", "mrnas and viral", "and viral genomic", "viral genomic rnas.", "genomic rnas. hiv", "rnas. hiv 1", "hiv 1 reverse", "1 reverse transcription", "reverse transcription takes", "transcription takes place", "takes place in", "place in the", "in the cytosol", "the cytosol of", "cytosol of a", "of a newly", "a newly infected", "newly infected host", "infected host cell", "host cell and", "cell and involves", "and involves multiple", "involves multiple steps", "multiple steps of", "steps of rna", "of rna synthesis", "rna synthesis and", "synthesis and degradation", "and degradation of", "degradation of the", "of the rna", "the rna strand", "rna strand of", "strand of rna:dna", "of rna:dna duplexes", "rna:dna duplexes mediated", "duplexes mediated by", "mediated by the", "by the hiv", "the hiv 1", "hiv 1 rt", "1 rt protein", "protein as", "as well as", "well as two", "as two template", "two template switches", "switches to", "to yield a", "yield a dna", "a dna duplex", "dna duplex colinear", "duplex colinear with", "colinear with the", "with the viral", "the viral genomic", "viral genomic rna", "genomic rna but", "rna but with", "but with additional", "with additional long", "additional long terminal", "long terminal repeat", "repeat ltr", "ltr sequence", "sequence motifs at", "motifs at both", "at both ends", "ends telesnitsky", "telesnitsky and goff", "and goff 1997", "1997 jonckheere", "jonckheere et al.", "et al. 2000", "al. 2000 .

              hiv", "2000 .

              hiv 1", ".

              hiv 1 rt", "1 rt has", "rt has two", "has two catalytic", "two catalytic activities", "catalytic activities essential", "activities essential for", "essential for transcription", "for transcription of", "transcription of a", "of a dna", "dna duplex copy", "duplex copy of", "copy of the", "of the viral", "viral genomic rna:", "genomic rna: a", "rna: a reverse", "a reverse transcriptase", "reverse transcriptase activity", "transcriptase activity and", "activity and an", "and an rnase", "an rnase h", "rnase h activity.", "h activity. the", "activity. the reverse", "the reverse transcriptase", "reverse transcriptase is", "transcriptase is primer", "is primer dependent", "primer dependent and", "dependent and can", "and can transcribe", "can transcribe both", "transcribe both rna", "both rna and", "rna and dna", "and dna templates", "dna templates in", "templates in a", "in a 5'", "a 5' 3'", "5' 3' direction.", "3' direction. the", "direction. the rnaseh", "the rnaseh acts", "rnaseh acts on", "acts on the", "on the rna", "rna:dna duplexes and", "duplexes and can", "and can catalyze", "can catalyze both", "catalyze both endo", "endo and", "and exonucleolytic cleavage", "exonucleolytic cleavage of", "cleavage of such", "of such an", "such an rna", "an rna strand.", "rna strand. rt", "strand. rt is", "rt is a", "is a heterodimer", "a heterodimer of", "heterodimer of 66", "of 66 and", "66 and 51", "and 51 kd", "51 kd polypeptides", "polypeptides both", "both generated by", "generated by cleavage", "by cleavage of", "cleavage of the", "of the hiv", "hiv 1 pol", "1 pol gene", "pol gene product:", "gene product: p66", "product: p66 contains", "p66 contains pol", "contains pol amino", "pol amino acid", "amino acid residues", "acid residues 599", "residues 599 1158", "1158 p51", "p51 contains residues", "contains residues 599", "residues 599 1038.", "599 1038. both", "1038. both active", "both active sites", "active sites of", "sites of the", "1 rt enzyme", "rt enzyme are", "enzyme are contained", "are contained in", "contained in the", "in the p66", "the p66 polypeptide", "polypeptide the", "the polymerase activity", "polymerase activity in", "activity in its", "in its aminoterminal", "its aminoterminal region", "region and", "and the rnase", "the rnase in", "rnase in its", "in its carboxyterminus.", "its carboxyterminus. the", "carboxyterminus. the p51", "the p51 subunit", "p51 subunit lacks", "subunit lacks an", "lacks an rnaseh", "an rnaseh domain", "domain and", "and while its", "while its polymerase", "its polymerase domain", "polymerase domain is", "domain is intact", "intact its", "its conformation in", "conformation in the", "in the p66:p51", "the p66:p51 heterodimer", "p66:p51 heterodimer occludes", "heterodimer occludes the", "occludes the active", "the active site", "site hughes", "hughes et al.", "et al. 1996", "1996 jacobo", "jacobo molina et", "molina et al.", "et al. 1993", "1993 kohlstaedt", "kohlstaedt et al.", "et al. 1992", "1992 wang", "wang et al.", "et al. 1994", "al. 1994 .

              the", "1994 .

              the process", ".

              the process of", "process of reverse", "of reverse transcription", "reverse transcription is", "transcription is outlined", "is outlined in", "outlined in the", "in the figure", "the figure below:", "figure below: viral", "below: viral genomic", "genomic rna and", "rna and primer", "and primer trna", "primer trna are", "trna are shown", "are shown in", "shown in black", "black \\minus\\", "\\minus\\ strand dna", "strand dna is", "dna is shown", "is shown in", "shown in red", "red and", "and \\plus\\ strand", "\\plus\\ strand dna", "shown in blue.", "the rna genome of", "rna genome of hiv", "genome of hiv 1", "hiv 1 like", "1 like that", "like that of other", "that of other retroviruses", "other retroviruses is", "retroviruses is reverse", "reverse transcribed baltimore", "transcribed baltimore 1970", "baltimore 1970 temin", "1970 temin and", "temin and mizutani 1970", "mizutani 1970 into", "1970 into double", "into double stranded dna", "stranded dna which", "dna which is", "which is then integrated", "is then integrated into", "then integrated into a", "integrated into a host", "into a host cell", "a host cell chromosome", "host cell chromosome and", "cell chromosome and transcribed", "chromosome and transcribed to", "and transcribed to yield", "transcribed to yield both", "to yield both viral", "yield both viral mrnas", "both viral mrnas and", "viral mrnas and viral", "mrnas and viral genomic", "and viral genomic rnas.", "viral genomic rnas. hiv", "genomic rnas. hiv 1", "rnas. hiv 1 reverse", "hiv 1 reverse transcription", "1 reverse transcription takes", "reverse transcription takes place", "transcription takes place in", "takes place in the", "place in the cytosol", "in the cytosol of", "the cytosol of a", "cytosol of a newly", "of a newly infected", "a newly infected host", "newly infected host cell", "infected host cell and", "host cell and involves", "cell and involves multiple", "and involves multiple steps", "involves multiple steps of", "multiple steps of rna", "steps of rna synthesis", "of rna synthesis and", "rna synthesis and degradation", "synthesis and degradation of", "and degradation of the", "degradation of the rna", "of the rna strand", "the rna strand of", "rna strand of rna:dna", "strand of rna:dna duplexes", "of rna:dna duplexes mediated", "rna:dna duplexes mediated by", "duplexes mediated by the", "mediated by the hiv", "by the hiv 1", "the hiv 1 rt", "hiv 1 rt protein", "rt protein as", "protein as well", "as well as two", "well as two template", "as two template switches", "template switches to", "switches to yield", "to yield a dna", "yield a dna duplex", "a dna duplex colinear", "dna duplex colinear with", "duplex colinear with the", "colinear with the viral", "with the viral genomic", "the viral genomic rna", "viral genomic rna but", "genomic rna but with", "rna but with additional", "but with additional long", "with additional long terminal", "additional long terminal repeat", "terminal repeat ltr", "ltr sequence motifs", "sequence motifs at both", "motifs at both ends", "both ends telesnitsky", "ends telesnitsky and", "telesnitsky and goff 1997", "goff 1997 jonckheere", "1997 jonckheere et", "jonckheere et al. 2000", "et al. 2000 .

              hiv", "al. 2000 .

              hiv 1", "2000 .

              hiv 1 rt", ".

              hiv 1 rt has", "1 rt has two", "rt has two catalytic", "has two catalytic activities", "two catalytic activities essential", "catalytic activities essential for", "activities essential for transcription", "essential for transcription of", "for transcription of a", "transcription of a dna", "of a dna duplex", "a dna duplex copy", "dna duplex copy of", "duplex copy of the", "copy of the viral", "of the viral genomic", "the viral genomic rna:", "viral genomic rna: a", "genomic rna: a reverse", "rna: a reverse transcriptase", "a reverse transcriptase activity", "reverse transcriptase activity and", "transcriptase activity and an", "activity and an rnase", "and an rnase h", "an rnase h activity.", "rnase h activity. the", "h activity. the reverse", "activity. the reverse transcriptase", "the reverse transcriptase is", "reverse transcriptase is primer", "transcriptase is primer dependent", "is primer dependent and", "primer dependent and can", "dependent and can transcribe", "and can transcribe both", "can transcribe both rna", "transcribe both rna and", "both rna and dna", "rna and dna templates", "and dna templates in", "dna templates in a", "templates in a 5'", "in a 5' 3'", "a 5' 3' direction.", "5' 3' direction. the", "3' direction. the rnaseh", "direction. the rnaseh acts", "the rnaseh acts on", "rnaseh acts on the", "acts on the rna", "on the rna strand", "of rna:dna duplexes and", "rna:dna duplexes and can", "duplexes and can catalyze", "and can catalyze both", "can catalyze both endo", "both endo and", "endo and exonucleolytic", "and exonucleolytic cleavage of", "exonucleolytic cleavage of such", "cleavage of such an", "of such an rna", "such an rna strand.", "an rna strand. rt", "rna strand. rt is", "strand. rt is a", "rt is a heterodimer", "is a heterodimer of", "a heterodimer of 66", "heterodimer of 66 and", "of 66 and 51", "66 and 51 kd", "and 51 kd polypeptides", "kd polypeptides both", "polypeptides both generated", "both generated by cleavage", "generated by cleavage of", "by cleavage of the", "cleavage of the hiv", "of the hiv 1", "the hiv 1 pol", "hiv 1 pol gene", "1 pol gene product:", "pol gene product: p66", "gene product: p66 contains", "product: p66 contains pol", "p66 contains pol amino", "contains pol amino acid", "pol amino acid residues", "amino acid residues 599", "acid residues 599 1158", "599 1158 p51", "1158 p51 contains", "p51 contains residues 599", "contains residues 599 1038.", "residues 599 1038. both", "599 1038. both active", "1038. both active sites", "both active sites of", "active sites of the", "sites of the hiv", "hiv 1 rt enzyme", "1 rt enzyme are", "rt enzyme are contained", "enzyme are contained in", "are contained in the", "contained in the p66", "in the p66 polypeptide", "p66 polypeptide the", "polypeptide the polymerase", "the polymerase activity in", "polymerase activity in its", "activity in its aminoterminal", "in its aminoterminal region", "aminoterminal region and", "region and the", "and the rnase in", "the rnase in its", "rnase in its carboxyterminus.", "in its carboxyterminus. the", "its carboxyterminus. the p51", "carboxyterminus. the p51 subunit", "the p51 subunit lacks", "p51 subunit lacks an", "subunit lacks an rnaseh", "lacks an rnaseh domain", "rnaseh domain and", "domain and while", "and while its polymerase", "while its polymerase domain", "its polymerase domain is", "polymerase domain is intact", "is intact its", "intact its conformation", "its conformation in the", "conformation in the p66:p51", "in the p66:p51 heterodimer", "the p66:p51 heterodimer occludes", "p66:p51 heterodimer occludes the", "heterodimer occludes the active", "occludes the active site", "active site hughes", "site hughes et", "hughes et al. 1996", "al. 1996 jacobo", "1996 jacobo molina", "jacobo molina et al.", "molina et al. 1993", "al. 1993 kohlstaedt", "1993 kohlstaedt et", "kohlstaedt et al. 1992", "al. 1992 wang", "1992 wang et", "wang et al. 1994", "et al. 1994 .

              the", "al. 1994 .

              the process", "1994 .

              the process of", ".

              the process of reverse", "process of reverse transcription", "of reverse transcription is", "reverse transcription is outlined", "transcription is outlined in", "is outlined in the", "outlined in the figure", "in the figure below:", "the figure below: viral", "figure below: viral genomic", "below: viral genomic rna", "viral genomic rna and", "genomic rna and primer", "rna and primer trna", "and primer trna are", "primer trna are shown", "trna are shown in", "are shown in black", "in black \\minus\\", "black \\minus\\ strand", "\\minus\\ strand dna is", "strand dna is shown", "dna is shown in", "is shown in red", "in red and", "red and \\plus\\", "and \\plus\\ strand dna", "\\plus\\ strand dna is", "is shown in blue.", "the rna genome of hiv", "rna genome of hiv 1", "of hiv 1 like", "hiv 1 like that", "1 like that of", "like that of other retroviruses", "of other retroviruses is", "other retroviruses is reverse", "retroviruses is reverse transcribed", "is reverse transcribed baltimore", "reverse transcribed baltimore 1970", "baltimore 1970 temin and", "1970 temin and mizutani", "and mizutani 1970 into", "mizutani 1970 into double", "1970 into double stranded", "double stranded dna which", "stranded dna which is", "dna which is then", "which is then integrated into", "is then integrated into a", "then integrated into a host", "integrated into a host cell", "into a host cell chromosome", "a host cell chromosome and", "host cell chromosome and transcribed", "cell chromosome and transcribed to", "chromosome and transcribed to yield", "and transcribed to yield both", "transcribed to yield both viral", "to yield both viral mrnas", "yield both viral mrnas and", "both viral mrnas and viral", "viral mrnas and viral genomic", "mrnas and viral genomic rnas.", "and viral genomic rnas. hiv", "viral genomic rnas. hiv 1", "genomic rnas. hiv 1 reverse", "rnas. hiv 1 reverse transcription", "hiv 1 reverse transcription takes", "1 reverse transcription takes place", "reverse transcription takes place in", "transcription takes place in the", "takes place in the cytosol", "place in the cytosol of", "in the cytosol of a", "the cytosol of a newly", "cytosol of a newly infected", "of a newly infected host", "a newly infected host cell", "newly infected host cell and", "infected host cell and involves", "host cell and involves multiple", "cell and involves multiple steps", "and involves multiple steps of", "involves multiple steps of rna", "multiple steps of rna synthesis", "steps of rna synthesis and", "of rna synthesis and degradation", "rna synthesis and degradation of", "synthesis and degradation of the", "and degradation of the rna", "degradation of the rna strand", "of the rna strand of", "the rna strand of rna:dna", "rna strand of rna:dna duplexes", "strand of rna:dna duplexes mediated", "of rna:dna duplexes mediated by", "rna:dna duplexes mediated by the", "duplexes mediated by the hiv", "mediated by the hiv 1", "by the hiv 1 rt", "the hiv 1 rt protein", "1 rt protein as", "rt protein as well", "protein as well as", "as well as two template", "well as two template switches", "two template switches to", "template switches to yield", "switches to yield a", "to yield a dna duplex", "yield a dna duplex colinear", "a dna duplex colinear with", "dna duplex colinear with the", "duplex colinear with the viral", "colinear with the viral genomic", "with the viral genomic rna", "the viral genomic rna but", "viral genomic rna but with", "genomic rna but with additional", "rna but with additional long", "but with additional long terminal", "with additional long terminal repeat", "long terminal repeat ltr", "repeat ltr sequence", "ltr sequence motifs at", "sequence motifs at both ends", "at both ends telesnitsky", "both ends telesnitsky and", "ends telesnitsky and goff", "and goff 1997 jonckheere", "goff 1997 jonckheere et", "1997 jonckheere et al.", "jonckheere et al. 2000 .

              hiv", "et al. 2000 .

              hiv 1", "al. 2000 .

              hiv 1 rt", "2000 .

              hiv 1 rt has", ".

              hiv 1 rt has two", "1 rt has two catalytic", "rt has two catalytic activities", "has two catalytic activities essential", "two catalytic activities essential for", "catalytic activities essential for transcription", "activities essential for transcription of", "essential for transcription of a", "for transcription of a dna", "transcription of a dna duplex", "of a dna duplex copy", "a dna duplex copy of", "dna duplex copy of the", "duplex copy of the viral", "copy of the viral genomic", "of the viral genomic rna:", "the viral genomic rna: a", "viral genomic rna: a reverse", "genomic rna: a reverse transcriptase", "rna: a reverse transcriptase activity", "a reverse transcriptase activity and", "reverse transcriptase activity and an", "transcriptase activity and an rnase", "activity and an rnase h", "and an rnase h activity.", "an rnase h activity. the", "rnase h activity. the reverse", "h activity. the reverse transcriptase", "activity. the reverse transcriptase is", "the reverse transcriptase is primer", "reverse transcriptase is primer dependent", "transcriptase is primer dependent and", "is primer dependent and can", "primer dependent and can transcribe", "dependent and can transcribe both", "and can transcribe both rna", "can transcribe both rna and", "transcribe both rna and dna", "both rna and dna templates", "rna and dna templates in", "and dna templates in a", "dna templates in a 5'", "templates in a 5' 3'", "in a 5' 3' direction.", "a 5' 3' direction. the", "5' 3' direction. the rnaseh", "3' direction. the rnaseh acts", "direction. the rnaseh acts on", "the rnaseh acts on the", "rnaseh acts on the rna", "acts on the rna strand", "on the rna strand of", "strand of rna:dna duplexes and", "of rna:dna duplexes and can", "rna:dna duplexes and can catalyze", "duplexes and can catalyze both", "and can catalyze both endo", "catalyze both endo and", "both endo and exonucleolytic", "endo and exonucleolytic cleavage", "and exonucleolytic cleavage of such", "exonucleolytic cleavage of such an", "cleavage of such an rna", "of such an rna strand.", "such an rna strand. rt", "an rna strand. rt is", "rna strand. rt is a", "strand. rt is a heterodimer", "rt is a heterodimer of", "is a heterodimer of 66", "a heterodimer of 66 and", "heterodimer of 66 and 51", "of 66 and 51 kd", "66 and 51 kd polypeptides", "51 kd polypeptides both", "kd polypeptides both generated", "polypeptides both generated by", "both generated by cleavage of", "generated by cleavage of the", "by cleavage of the hiv", "cleavage of the hiv 1", "of the hiv 1 pol", "the hiv 1 pol gene", "hiv 1 pol gene product:", "1 pol gene product: p66", "pol gene product: p66 contains", "gene product: p66 contains pol", "product: p66 contains pol amino", "p66 contains pol amino acid", "contains pol amino acid residues", "pol amino acid residues 599", "amino acid residues 599 1158", "residues 599 1158 p51", "599 1158 p51 contains", "1158 p51 contains residues", "p51 contains residues 599 1038.", "contains residues 599 1038. both", "residues 599 1038. both active", "599 1038. both active sites", "1038. both active sites of", "both active sites of the", "active sites of the hiv", "sites of the hiv 1", "of the hiv 1 rt", "the hiv 1 rt enzyme", "hiv 1 rt enzyme are", "1 rt enzyme are contained", "rt enzyme are contained in", "enzyme are contained in the", "are contained in the p66", "contained in the p66 polypeptide", "the p66 polypeptide the", "p66 polypeptide the polymerase", "polypeptide the polymerase activity", "the polymerase activity in its", "polymerase activity in its aminoterminal", "activity in its aminoterminal region", "its aminoterminal region and", "aminoterminal region and the", "region and the rnase", "and the rnase in its", "the rnase in its carboxyterminus.", "rnase in its carboxyterminus. the", "in its carboxyterminus. the p51", "its carboxyterminus. the p51 subunit", "carboxyterminus. the p51 subunit lacks", "the p51 subunit lacks an", "p51 subunit lacks an rnaseh", "subunit lacks an rnaseh domain", "an rnaseh domain and", "rnaseh domain and while", "domain and while its", "and while its polymerase domain", "while its polymerase domain is", "its polymerase domain is intact", "domain is intact its", "is intact its conformation", "intact its conformation in", "its conformation in the p66:p51", "conformation in the p66:p51 heterodimer", "in the p66:p51 heterodimer occludes", "the p66:p51 heterodimer occludes the", "p66:p51 heterodimer occludes the active", "heterodimer occludes the active site", "the active site hughes", "active site hughes et", "site hughes et al.", "et al. 1996 jacobo", "al. 1996 jacobo molina", "1996 jacobo molina et", "jacobo molina et al. 1993", "et al. 1993 kohlstaedt", "al. 1993 kohlstaedt et", "1993 kohlstaedt et al.", "et al. 1992 wang", "al. 1992 wang et", "1992 wang et al.", "wang et al. 1994 .

              the", "et al. 1994 .

              the process", "al. 1994 .

              the process of", "1994 .

              the process of reverse", ".

              the process of reverse transcription", "process of reverse transcription is", "of reverse transcription is outlined", "reverse transcription is outlined in", "transcription is outlined in the", "is outlined in the figure", "outlined in the figure below:", "in the figure below: viral", "the figure below: viral genomic", "figure below: viral genomic rna", "below: viral genomic rna and", "viral genomic rna and primer", "genomic rna and primer trna", "rna and primer trna are", "and primer trna are shown", "primer trna are shown in", "trna are shown in black", "shown in black \\minus\\", "in black \\minus\\ strand", "black \\minus\\ strand dna", "\\minus\\ strand dna is shown", "strand dna is shown in", "dna is shown in red", "shown in red and", "in red and \\plus\\", "red and \\plus\\ strand", "and \\plus\\ strand dna is", "\\plus\\ strand dna is shown", "dna is shown in blue." ] }, { "record_id": "GLY_000594_1_1263", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162594", "r hsa", "hsa 162594", "r hsa 162594" ] }, { "record_id": "GLY_000594_1_1263", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "early phase", "phase of", "of hiv", "hiv life", "life cycle", "early phase of", "phase of hiv", "of hiv life", "hiv life cycle", "early phase of hiv", "phase of hiv life", "of hiv life cycle", "early phase of hiv life", "phase of hiv life cycle", "in the", "the early", "early phase", "phase ", " of", "hiv lifecycle", "an active", "active virion", "virion binds", "binds and", "and enters", "enters a", "a target", "target cell", "cell mainly", "mainly by", "by specific", "specific interactions", "interactions of", "of the", "the viral", "viral envelope", "envelope proteins", "proteins with", "with host", "host cell", "cell surface", "surface receptors.", "the virion", "virion core", "core is", "is uncoated", "uncoated to", "to expose", "expose a", "a viral", "viral nucleoprotein", "nucleoprotein complex", "complex containing", "containing rna", "rna and", "and viral", "viral proteins.", "hiv rna", "rna genome", "genome is", "is reverse", "reverse transcribed", "transcribed by", "by the", "viral reverse", "reverse transcriptase", "transcriptase to", "to form", "form a", "a cdna", "cdna copy", "that gets", "gets inserted", "inserted into", "into host", "cell dna.", "viral integrase", "integrase enzyme", "enzyme is", "is vital", "vital to", "to carry", "carry out", "out the", "the integration", "integration of", "viral cdna", "cdna into", "into the", "the host", "host genome.", "host dna", "dna repair", "repair enzymes", "enzymes probably", "probably repair", "repair the", "the breaks", "breaks in", "in dna", "dna at", "at the", "the sites", "sites of", "of integration.", "in the early", "the early phase", "early phase ", "phase of", " of hiv", "of hiv lifecycle", "lifecycle an", "an active virion", "active virion binds", "virion binds and", 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"form a cdna", "a cdna copy", "copy that", "that gets inserted", "gets inserted into", "inserted into host", "into host cell", "host cell dna.", "dna. the", "the viral integrase", "viral integrase enzyme", "integrase enzyme is", "enzyme is vital", "is vital to", "vital to carry", "to carry out", "carry out the", "out the integration", "the integration of", "integration of the", "the viral cdna", "viral cdna into", "cdna into the", "into the host", "the host genome.", "genome. the", "the host dna", "host dna repair", "dna repair enzymes", "repair enzymes probably", "enzymes probably repair", "probably repair the", "repair the breaks", "the breaks in", "breaks in dna", "in dna at", "dna at the", "at the sites", "the sites of", "sites of integration.", "in the early phase", "the early phase ", "early phase of", "phase of hiv", " of hiv lifecycle", "hiv lifecycle an", "lifecycle an active", "an active virion binds", "active virion binds and", "virion binds and enters", "binds and enters a", "and enters a target", "enters a target cell", "a target cell mainly", "target cell mainly by", "cell mainly by specific", "mainly by specific interactions", "by specific interactions of", "specific interactions of the", "interactions of the viral", "of the viral envelope", "the viral envelope proteins", "viral envelope proteins with", "envelope proteins with host", "proteins with host cell", "with host cell surface", "host cell surface receptors.", "surface receptors. the", "receptors. the virion", "the virion core is", "virion core is uncoated", "core is uncoated to", "is uncoated to expose", "uncoated to expose a", "to expose a viral", "expose a viral nucleoprotein", "a viral nucleoprotein complex", "viral nucleoprotein complex containing", "nucleoprotein complex containing rna", "complex containing rna and", "containing rna and viral", "rna and viral proteins.", "viral proteins. hiv", "proteins. hiv rna", "hiv rna genome is", "rna genome is reverse", "genome is reverse transcribed", "is reverse transcribed by", "reverse transcribed by the", "transcribed by the viral", "by the viral reverse", "the viral reverse transcriptase", "viral reverse transcriptase to", "reverse transcriptase to form", "transcriptase to form a", "to form a cdna", "form a cdna copy", "cdna copy that", "copy that gets", "that gets inserted into", "gets inserted into host", "inserted into host cell", "into host cell dna.", "cell dna. the", "dna. the viral", "the viral integrase enzyme", "viral integrase enzyme is", "integrase enzyme is vital", "enzyme is vital to", "is vital to carry", "vital to carry out", "to carry out the", "carry out the integration", "out the integration of", "the integration of the", "integration of the viral", "of the viral cdna", "the viral cdna into", "viral cdna into the", "cdna into the host", "into the host genome.", "host genome. the", "genome. the host", "the host dna repair", "host dna repair enzymes", "dna repair enzymes probably", "repair enzymes probably repair", "enzymes probably repair the", "probably repair the breaks", "repair the breaks in", "the breaks in dna", "breaks in dna at", "in dna at the", "dna at the sites", "at the sites of", "the sites of integration.", "in the early phase ", "the early phase of", "early phase of hiv", "phase of hiv lifecycle", "of hiv lifecycle an", "hiv lifecycle an active", "lifecycle an active virion", "an active virion binds and", "active virion binds and enters", "virion binds and enters a", "binds and enters a target", "and enters a target cell", "enters a target cell mainly", "a target cell mainly by", "target cell mainly by specific", "cell mainly by specific interactions", "mainly by specific interactions of", "by specific interactions of the", "specific interactions of the viral", "interactions of the viral envelope", "of the viral envelope proteins", "the viral envelope proteins with", "viral envelope proteins with host", "envelope proteins with host cell", "proteins with host cell surface", "with host cell surface receptors.", "cell surface receptors. the", "surface receptors. the virion", "receptors. the virion core", "the virion core is uncoated", "virion core is uncoated to", "core is uncoated to expose", "is uncoated to expose a", "uncoated to expose a viral", "to expose a viral nucleoprotein", "expose a viral nucleoprotein complex", "a viral nucleoprotein complex containing", "viral nucleoprotein complex containing rna", "nucleoprotein complex containing rna and", "complex containing rna and viral", "containing rna and viral proteins.", "and viral proteins. hiv", "viral proteins. hiv rna", "proteins. hiv rna genome", "hiv rna genome is reverse", "rna genome is reverse transcribed", "genome is reverse transcribed by", "is reverse transcribed by the", "reverse transcribed by the viral", "transcribed by the viral reverse", "by the viral reverse transcriptase", "the viral reverse transcriptase to", "viral reverse transcriptase to form", "reverse transcriptase to form a", "transcriptase to form a cdna", "to form a cdna copy", "a cdna copy that", "cdna copy that gets", "copy that gets inserted", "that gets inserted into host", "gets inserted into host cell", "inserted into host cell dna.", "host cell dna. the", "cell dna. the viral", "dna. the viral integrase", "the viral integrase enzyme is", "viral integrase enzyme is vital", "integrase enzyme is vital to", "enzyme is vital to carry", "is vital to carry out", "vital to carry out the", "to carry out the integration", "carry out the integration of", "out the integration of the", "the integration of the viral", "integration of the viral cdna", "of the viral cdna into", "the viral cdna into the", "viral cdna into the host", "cdna into the host genome.", "the host genome. the", "host genome. the host", "genome. the host dna", "the host dna repair enzymes", "host dna repair enzymes probably", "dna repair enzymes probably repair", "repair enzymes probably repair the", "enzymes probably repair the breaks", "probably repair the breaks in", "repair the breaks in dna", "the breaks in dna at", "breaks in dna at the", "in dna at the sites", "dna at the sites of", "at the sites of integration." ] }, { "record_id": "GLY_000594_1_1264", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "162599", "r hsa", "hsa 162599", "r hsa 162599" ] }, { "record_id": "GLY_000594_1_1264", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "late phase", "phase of", "of hiv", "hiv life", "life cycle", "late phase of", "phase of hiv", "of hiv life", "hiv life cycle", "late phase of hiv", "phase of hiv life", "of hiv life cycle", "late phase of hiv life", "phase of hiv life cycle", "the late", "of the", "the hiv", "hiv 1", "1 life", "cycle includes", "includes the", "the regulated", "regulated expression", "expression of", "hiv gene", "gene products", "products and", "and the", "the assembly", "assembly of", "of viral", 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"requires the", "the function", "function of", "1 tat", "tat protein", "protein which", "which promotes", "promotes elongation", "elongation of", "reviewed in", "in karn", "taube et", "al. 1999", "liou et", "barboric and", "and peterlin", "peterlin 2005", "2005 .", "1 rev", "rev protein", "protein is", "is required", "required post", "post transcriptionally", "transcriptionally for", "for the", "the expression", "late genes.", "genes. rev", "rev functions", "functions by", "by promoting", "promoting the", "the nuclear", "nuclear export", "export of", "of unspliced", "unspliced and", "and partially", "partially spliced", "spliced transcripts", "transcripts that", "that encode", "encode the", "the major", "major structural", "structural proteins", "proteins gag", "pol and", "and env", "the majority", "majority of", "the accessory", "accessory proteins", "malim et", "in pollard", "pollard and", "and malim", "malim 1998", "1998 .", "the late phase", "phase of the", "of the hiv", "the hiv 1", "hiv 1 life", "1 life cycle", "life cycle includes", "cycle includes the", "includes the regulated", "the regulated expression", "regulated expression of", "expression of the", "the hiv gene", "hiv gene products", "gene products and", "products and the", "and the assembly", "the assembly of", "assembly of viral", "of viral particles.", "viral particles. the", "particles. the assembly", "of viral particles", "viral particles will", "particles will be", "will be covered", "be covered in", "covered in a", "in a later", "a later release", "later release of", "release of reactome.", "of reactome. hiv", "reactome. hiv 1", "hiv 1 gene", "1 gene expression", "gene expression is", "expression is regulated", "is regulated by", "regulated by both", "by both cellular", "both cellular and", "cellular and viral", "and viral proteins.", "viral proteins. although", "proteins. although the", "although the initial", "the initial activation", "initial activation of", "activation of the", "hiv 1 transcription", "1 transcription is", "transcription is facilitated", "is facilitated by", "facilitated by cellular", "by cellular transcription", "cellular transcription factors", "transcription factors including", "factors including nf", "including nf kappa", "nf kappa b", "b nabel", "nabel and baltimore", "baltimore 1987", "this activation results", "activation results in", "results in the", "in the production", "the production of", "production of primarily", "of primarily short", "primarily short transcripts", "transcripts kao", "kao et al.", "al. 1987", "1987 . expression", ". expression of", "expression of high", "of high levels", "high levels of", "levels of the", "of the full", "the full length", "full length hiv", "length hiv 1", "hiv 1 transcript", "1 transcript requires", "transcript requires the", "requires the function", "the function of", "function of the", "hiv 1 tat", "1 tat protein", "tat protein which", "protein which promotes", "which promotes elongation", "promotes elongation of", "elongation of the", "transcript reviewed", "reviewed in karn", "karn 1999", "1999 taube", "taube et al.", "et al. 1999", "1999 liou", "liou et al.", "al. 2004", "2004 barboric", "barboric and peterlin", "and peterlin 2005", "peterlin 2005 .", ". the", "hiv 1 rev", "1 rev protein", "rev protein is", "protein is required", "is required post", "required post transcriptionally", "post transcriptionally for", "transcriptionally for the", "for the expression", "the expression of", "of the late", "the late genes.", "late genes. rev", "genes. rev functions", "rev functions by", "functions by promoting", "by promoting the", "promoting the nuclear", "the nuclear export", "nuclear export of", "export of unspliced", "of unspliced and", "unspliced and partially", "and partially spliced", "partially spliced transcripts", "spliced transcripts that", "transcripts that encode", "that encode the", "encode the major", "the major structural", "major structural proteins", "structural proteins gag", "gag pol", "pol and env", "env and", "and the majority", "the majority of", "majority of the", "of the accessory", "the accessory proteins", "proteins malim", "malim et al.", "al. 1989", "reviewed in pollard", "in pollard and", "pollard and malim", "and malim 1998", "malim 1998 .", "the late phase of", "late phase of the", "phase of the hiv", "of the hiv 1", "the hiv 1 life", "hiv 1 life cycle", "1 life cycle includes", "life cycle includes the", "cycle includes the regulated", "includes the regulated expression", "the regulated expression of", "regulated expression of the", "expression of the hiv", "of the hiv gene", "the hiv gene products", "hiv gene products and", "gene products and the", "products and the assembly", "and the assembly of", "the assembly of viral", "assembly of viral particles.", "of viral particles. the", "viral particles. the assembly", "particles. the assembly of", "assembly of viral particles", "of viral particles will", "viral particles will be", "particles will be covered", "will be covered in", "be covered in a", "covered in a later", "in a later release", "a later release of", "later release of reactome.", "release of reactome. hiv", "of reactome. hiv 1", "reactome. hiv 1 gene", "hiv 1 gene expression", "1 gene expression is", "gene expression is regulated", "expression is regulated by", "is regulated by both", "regulated by both cellular", "by both cellular and", "both cellular and viral", "cellular and viral proteins.", "and viral proteins. although", "viral proteins. although the", "proteins. although the initial", "although the initial activation", "the initial activation of", "initial activation of the", "activation of the hiv", "the hiv 1 transcription", "hiv 1 transcription is", "1 transcription is facilitated", "transcription is facilitated by", "is facilitated by cellular", "facilitated by cellular transcription", "by cellular transcription factors", "cellular transcription factors including", "transcription factors 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              sting", "worldwide.

              sting has", "has been", "been also", "also implicated", "implicated in", "in type", "ifn response", "response which", "which was", "was stimulated", "stimulated by", "by fusion", "fusion of", "of viral", "viral and", "and target", "target cell", "cell membrane", "membrane in", "in a", "a manner", "manner independent", "independent of", "of dna", "rna and", "and viral", "viral capsid", "holm ck", "ck et", "al 2012", "2012 .

              under", ".

              under steady", "steady state", "state conditions", "is positioned", "positioned at", "at the", "the translocon", "translocon complex", "complex within", "within the", "the er", "er membrane.", "membrane. however", "however upon", "upon stimulation", "stimulation with", "with intracellular", "intracellular dna", "dna it", "it translocates", "translocates from", "from er", "er to", "to perinuclear", "perinuclear vesicles", "vesicles via", "via the", "the golgi", "golgi by", "by mechanisms", "mechanisms that", "that remain", "remain unclear", "saitoh t", "t et", "2009 .", ". mouse", "mouse sting", "sting trafficking", "trafficking in", "in dsdna", "dsdna stimulated", "stimulated mouse", "mouse embryonic", "embryonic fibroblasts", "cells was", "was found", "found to", "to depend", "depend on", "on autophagy", "autophagy related", "related gene", "gene 9a", "2009 .

              sting", ".

              sting was", "was reported", "reported to", "to function", "function as", "as a", "a signaling", "signaling adaptor", "adaptor or", "or coreceptor", "coreceptor in", "to cytosolic", "cytosolic dsdna", "unterholzner l", "l et", "zhang z", "z et", "2011 .", ". sting", "sting was", "was also", "also shown", "a direct", "direct dna", "dna sensor", "sensor to", "to induce", "induce the", "the innate", "innate immune", "immune response", "response in", "human telomerase", "telomerase fibroblasts", "htert bj1", "and murine", "murine embryonic", "abe t", "al. 2013", "2013 .", ". additionally", "is thought", "thought to", "direct sensor", "sensor of", "of cyclic", "cyclic dinucleotides.", "dinucleotides. sting", "was shown", "to interact", "interact directly", "directly with", "with c", "c di", "di gmp", "gmp in", "human embryonic", "embryonic kidney", "kidney hek293t", "hek293t cell", "cell lysates", "burdette dl", "dl et", ". once", "once sting", "is stimulated", "its c", "c terminus", "terminus serves", "serves as", "signaling scaffold", "scaffold to", "to recruit", "recruit irf3", "irf3 and", "and tbk1", "which leads", "leads to", "to tbk1", "tbk1 dependent", "dependent phosphorylation", "phosphorylation of", "of irf3", "tanaka y", "y and", "and chen", "chen zj", "zj 2012", "2012 .

              mouse", "but not", "not human", "human sting", "can also", "also bind", "bind vascular", "vascular disrupting", "disrupting agents", "agents 5", "5 6", "6 dimethylxanthenone", "dimethylxanthenone 4", "4 acetic", "acetic acid", "and the", "the antiviral", "antiviral small", "small molecule", "molecule 10", "10 carboxymethyl", "carboxymethyl 9", "9 acridanone", "induce type", "suggesting a", "a species", "species specific", "specific drug", "drug effect", "effect on", "on the", "the sting", "mediated host", "host response", "conlon j", "j et", "cavlar t", "sting stimulator", "stimulator of ifn", "of ifn genes", "genes also", "also known as", "known as mita/eris/mpys/tmem173", "mita/eris/mpys/tmem173 is", "is an endoplasmic", "an endoplasmic reticulum", "reticulum er", "er resident", "resident which", "which is required", "is required for", "required for effective", "for effective type", "effective type i", "type i ifn", "i ifn production", "ifn production in", "production in response", "in response to", "response to nucleic", "to nucleic acids.", "nucleic acids. indeed", "indeed select", "select pathogen derived", "pathogen derived dna", "derived dna or", "dna or rna", "or rna were", "rna were shown", "were shown to", "shown to activate", "to activate sting", "activate sting in", "sting in human", "in human and", "human and mouse", "and mouse cells", "cells ishikawa", "ishikawa h and", "h and barber", "and barber gn", "barber gn 2008", "2008 ishikawa", "ishikawa h et", "h et al.", "et al. 2009", "2009 sun", "sun w et", "w et al.", "2009 prantner", "prantner d et", "d et al.", "et al. 2010", "al. 2010 .", "2010 . importantly", "importantly in", "in vitro studies", "vitro studies have", "studies have shown", "have shown that", "shown that sting", "that sting is", "sting is essential", "is essential for", "essential for mycobacterium", "for mycobacterium tuberculosis", "tuberculosis manzanillo", "manzanillo ps et", "ps et al.", "et al. 2012", "falciparum sharma", "sharma s et", "s et al.", "et al. 2011", "2011 and", "and human immunodeficiency", "human immunodeficiency virus", "virus hiv", "hiv induced", "induced type i", "production yan", "yan n et", "n et al", "et al 2010", "al 2010 .", "2010 . mycobacterium", ". mycobacterium tuberculosis", "tuberculosis plasmodium", "plasmodium falciparum and", "falciparum and hiv", "and hiv are", "hiv are three", "are three deadliest", "three deadliest pathogens", "pathogens which", "which kill millions", "kill millions of", "millions of people", "of people each", "people each year", "each year worldwide.

              sting", "year worldwide.

              sting has", "worldwide.

              sting has been", "has been also", "been also implicated", "also implicated in", "implicated in type", "in type i", "i ifn response", "ifn response which", "response which was", "which was stimulated", "was stimulated by", "stimulated by fusion", "by fusion of", "fusion of viral", "of viral and", "viral and target", "and target cell", "target cell membrane", "cell membrane in", "membrane in a", "in a manner", "a manner independent", "manner independent of", "independent of dna", "dna rna", "rna and viral", "and viral capsid", "holm ck et", "ck et al", "et al 2012", "al 2012 .

              under", "2012 .

              under steady", ".

              under steady state", "steady state conditions", "conditions sting", "sting is positioned", "is positioned at", "positioned at the", "at the translocon", "the translocon complex", "translocon complex within", "complex within the", "within the er", "the er membrane.", "er membrane. however", "membrane. however upon", "however upon stimulation", "upon stimulation with", "stimulation with intracellular", "with intracellular dna", "intracellular dna it", "dna it translocates", "it translocates from", "translocates from er", "from er to", "er to perinuclear", "to perinuclear vesicles", "perinuclear vesicles via", "vesicles via the", "via the golgi", "the golgi by", "golgi by mechanisms", "by mechanisms that", "mechanisms that remain", "that remain unclear", "unclear ishikawa", "2008 sun", "2009 ishikawa", "2009 saitoh", "saitoh t et", "t et al.", "al. 2009 .", "2009 . mouse", ". mouse sting", "mouse sting trafficking", "sting trafficking in", "trafficking in dsdna", "in dsdna stimulated", "dsdna stimulated mouse", "stimulated mouse embryonic", "mouse embryonic fibroblasts", "fibroblasts mef", "mef cells", "cells was found", "was found to", "found to depend", "to depend on", "depend on autophagy", "on autophagy related", "autophagy related gene", "related gene 9a", "9a atg9a", "al. 2009 .

              sting", "2009 .

              sting was", ".

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              mouse", ".

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              sting", "each year worldwide.

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              under", "al 2012 .

              under steady", "2012 .

              under steady state", ".

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              sting", "al. 2009 .

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              mouse", "2012 .

              mouse but", ".

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              sting", "people each year worldwide.

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              under", "et al 2012 .

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uroporphyringen", "uroporphyringen i", "i which", "then enzymatically", "enzymatically decarboxylated", "decarboxylated to", "to coproporphyrinogen", "coproporphyrinogen i", "which cannot", "cannot be", "be metabolized", "metabolized further", "further in", "in humans.", "humans. also", "lead can", "can inactivate", "inactivate alad", "the enzyme", "enzyme that", "that catalyzes", "catalyzes pbg", "pbg synthesis", "and ferrochelatase", "catalyzes heme", "heme synthesis", "ponka et", "al. 1999", "aijoka et", "al. 2006", "2006 .

              the", ".

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              the", "2006 .

              the porphyrias", ".

              the porphyrias are", "porphyrias are disorders", "are disorders that", "disorders that arise", "that arise from", "arise from defects", "from defects in", "defects in the", "in the enzymes", "the enzymes of", "enzymes of heme", "of heme biosynthesis.", "heme biosynthesis. defective", "biosynthesis. defective pathway", "defective pathway enzymes", "pathway enzymes after", "enzymes after ala", "after ala synthase", "ala synthase result", "synthase result in", "result in accumulated", "in accumulated substrates", "accumulated substrates which", "substrates which can", "which can cause", "can cause either", "cause either skin", "either skin problems", "problems neurological", "complications or", "or both due", "both due to", "due to their", "to their toxicity", "their toxicity in", "toxicity in higher", "in higher concentrations.", "higher concentrations. they", "concentrations. they are", "they are broadly", "are broadly classified", "broadly classified as", "classified as hepatic", "as hepatic porphyrias", "hepatic porphyrias or", "porphyrias or erythropoietic", "or erythropoietic porphyrias", "porphyrias based", "based on the", "on the site", "the site of", "site of the", "of the overproduction", "the overproduction of", "overproduction of the", "of the substrate.", "the substrate. each", "substrate. each defect", "each defect is", "defect is described", "is described together", "described together with", "together with the", "with the reaction", "the reaction it", "reaction it affects", "affects peoc'h", "peoc'h et al.", "et al. 2016", "al. 2016 .", "although heme is synthesised", "heme is synthesised in", "is synthesised in virtually", "synthesised in virtually all", "in virtually all tissues", "all tissues the", "tissues the principal", "the principal sites of", "principal sites of synthesis", "sites of synthesis are", "of synthesis are erythroid", "synthesis are erythroid cells", "erythroid cells ~85%", "~85% and hepatocytes", "and hepatocytes most", "hepatocytes most of", "most of the remainder", "of the remainder .", "the remainder . eight", "remainder . eight enzymes", ". eight enzymes are", "eight enzymes are involved", "enzymes are involved in", "are involved in heme", "involved in heme biosynthesis", "heme biosynthesis four", "biosynthesis four each", "four each in the", "each in the mitochondria", "in the mitochondria and", "the mitochondria and the", "mitochondria and the cytosol", "the cytosol layer", "cytosol layer et", "layer et al. 2010", "et al. 2010 .", "al. 2010 . the", "2010 . the process", ". the process starts", "the process starts in", "process starts in the", "starts in the mitochondria", "in the mitochondria with", "the mitochondria with the", "mitochondria with the condensation", "with the condensation of", "the condensation of succinyl", "condensation of succinyl coa", "succinyl coa from", "coa from the", "from the tca cycle", "tca cycle and", "cycle and glycine", "and glycine to form", "glycine to form 5", "to form 5 aminolevulinate", "5 aminolevulinate ala", "aminolevulinate ala .", "ala . the next", ". the next four", "the next four steps", "next four steps take", "four steps take place", "steps take place in", "take place in the", "place in the cytosol.", "in the cytosol. two", "the cytosol. two molecules", "cytosol. two molecules of", "two molecules of ala", "molecules of ala are", "of ala are condensed", "ala are condensed to", "are condensed to form", "condensed to form the", "to form the monopyrrole", "form the monopyrrole porphobilinogen", "monopyrrole porphobilinogen pbg", "porphobilinogen pbg .", "pbg . the next", ". the next two", "the next two steps", "next two steps convert", "two steps convert four", "steps convert four molecules", "convert four molecules of", "four molecules of pbg", "molecules of pbg into", "of pbg into the", "pbg into the cyclic", "into the cyclic tetrapyrrole", "the cyclic tetrapyrrole uroporphyringen", "cyclic tetrapyrrole uroporphyringen iii", "uroporphyringen iii which", "iii which is", "which is then decarboxylated", "is then decarboxylated into", "then decarboxylated into coproporphyrinogen", "decarboxylated into coproporphyrinogen iii.", "into coproporphyrinogen iii. the", "coproporphyrinogen iii. the last", "iii. the last three", "the last three steps", "last three steps occur", "three steps occur in", "steps occur in the", "occur in the mitochondria", "the mitochondria and involve", "mitochondria and involve modifications", "and involve modifications to", "involve modifications to the", "modifications to the tetrapyrrole", "to the tetrapyrrole side", "the tetrapyrrole side chains", "tetrapyrrole side chains and", "side chains and finally", "and finally insertion", "finally insertion of", "insertion of iron. in", "of iron. in addition", "iron. in addition to", "in addition to these", "addition to these synthetic", "to these synthetic steps", "synthetic steps a", "steps a spontaneous", "a spontaneous cytosolic reaction", "spontaneous cytosolic reaction allows", "cytosolic reaction allows the", "reaction allows the formation", "allows the formation of", "the formation of uroporphyringen", "formation of uroporphyringen i", "of uroporphyringen i which", "uroporphyringen i which is", "i which is then", "which is then enzymatically", "is then enzymatically decarboxylated", "then enzymatically decarboxylated to", "enzymatically decarboxylated to coproporphyrinogen", "decarboxylated to coproporphyrinogen i", "coproporphyrinogen i which", "i which cannot", "which cannot be metabolized", "cannot be metabolized further", "be metabolized further in", "metabolized further in humans.", "further in humans. also", "humans. also lead", "also lead can", "lead can inactivate alad", "inactivate alad the", "alad the enzyme", "the enzyme that catalyzes", "enzyme that catalyzes pbg", "that catalyzes pbg synthesis", "pbg synthesis and", "synthesis and ferrochelatase", "and ferrochelatase the", "ferrochelatase the enzyme", "enzyme that catalyzes heme", "that catalyzes heme synthesis", "heme synthesis ponka", "synthesis ponka et", "ponka et al. 1999", "al. 1999 aijoka", "1999 aijoka et", "aijoka et al. 2006", "et al. 2006 .

              the", "al. 2006 .

              the porphyrias", "2006 .

              the porphyrias are", ".

              the porphyrias are disorders", "porphyrias are disorders that", "are disorders that arise", "disorders that arise from", "that arise from defects", "arise from defects in", "from defects in the", "defects in the enzymes", "in the enzymes of", "the enzymes of heme", "enzymes of heme biosynthesis.", "of heme biosynthesis. defective", "heme biosynthesis. defective pathway", "biosynthesis. defective pathway enzymes", "defective pathway enzymes after", "pathway enzymes after ala", "enzymes after ala synthase", "after ala synthase result", "ala synthase result in", "synthase result in accumulated", "result in accumulated substrates", "in accumulated substrates which", "accumulated substrates which can", "substrates which can cause", "which can cause either", "can cause either skin", "cause either skin problems", "skin problems neurological", "problems neurological complications", "neurological complications or", "complications or both", "or both due to", "both due to their", "due to their toxicity", "to their toxicity in", "their toxicity in higher", "toxicity in higher concentrations.", "in higher concentrations. they", "higher concentrations. they are", "concentrations. they are broadly", "they are broadly classified", "are broadly classified as", "broadly classified as hepatic", "classified as hepatic porphyrias", "as hepatic porphyrias or", "hepatic porphyrias or erythropoietic", "porphyrias or erythropoietic porphyrias", "erythropoietic porphyrias based", "porphyrias based on", "based on the site", "on the site of", "the site of the", "site of the overproduction", "of the overproduction of", "the overproduction of the", "overproduction of the substrate.", "of the substrate. each", "the substrate. each defect", "substrate. each defect is", "each defect is described", "defect is described together", "is described together with", "described together with the", "together with the reaction", "with the reaction it", "the reaction it affects", "it affects peoc'h", "affects peoc'h et", "peoc'h et al. 2016", "et al. 2016 .", "although heme is synthesised in", "heme is synthesised in virtually", "is synthesised in virtually all", "synthesised in virtually all tissues", "virtually all tissues the", "all tissues the principal", "tissues the principal sites", "the principal sites of synthesis", "principal sites of synthesis are", "sites of synthesis are erythroid", "of synthesis are erythroid cells", "are erythroid cells ~85%", "cells ~85% and", "and hepatocytes most of", "hepatocytes most of the", "most of the remainder .", "of the remainder . eight", "the remainder . eight enzymes", "remainder . eight enzymes are", ". eight enzymes are involved", "eight enzymes are involved in", "enzymes are involved in heme", "are involved in heme biosynthesis", "in heme biosynthesis four", "heme biosynthesis four each", "biosynthesis four each in", "four each in the mitochondria", "each in the mitochondria and", "in the mitochondria and the", "the mitochondria and the cytosol", "and the cytosol layer", "the cytosol layer et", "cytosol layer et al.", "layer et al. 2010 .", "et al. 2010 . the", "al. 2010 . the process", "2010 . the process starts", ". the process starts in", "the process starts in the", "process starts in the mitochondria", "starts in the mitochondria with", "in the mitochondria with the", "the mitochondria with the condensation", "mitochondria with the condensation of", "with the condensation of succinyl", "the condensation of succinyl coa", "of succinyl coa from", "succinyl coa from the", "coa from the tca", "the tca cycle and", "tca cycle and glycine", "cycle and glycine to", "and glycine to form 5", "glycine to form 5 aminolevulinate", "form 5 aminolevulinate ala", "5 aminolevulinate ala .", "aminolevulinate ala . the", "ala . the next four", ". the next four steps", "the next four steps take", "next four steps take place", "four steps take place in", "steps take place in the", "take place in the cytosol.", "place in the cytosol. two", "in the cytosol. two molecules", "the cytosol. two molecules of", "cytosol. two molecules of ala", "two molecules of ala are", "molecules of ala are condensed", "of ala are condensed to", "ala are condensed to form", "are condensed to form the", "condensed to form the monopyrrole", "to form the monopyrrole porphobilinogen", "the monopyrrole porphobilinogen pbg", "monopyrrole porphobilinogen pbg .", "porphobilinogen pbg . the", "pbg . the next two", ". the next two steps", "the next two steps convert", "next two steps convert four", "two steps convert four molecules", "steps convert four molecules of", "convert four molecules of pbg", "four molecules of pbg into", "molecules of pbg into the", "of pbg into the cyclic", "pbg into the cyclic tetrapyrrole", "into the cyclic tetrapyrrole uroporphyringen", "the cyclic tetrapyrrole uroporphyringen iii", "tetrapyrrole uroporphyringen iii which", "uroporphyringen iii which is", "iii which is then", "which is then decarboxylated into", "is then decarboxylated into coproporphyrinogen", "then decarboxylated into coproporphyrinogen iii.", "decarboxylated into coproporphyrinogen iii. the", "into coproporphyrinogen iii. the last", "coproporphyrinogen iii. the last three", "iii. the last three steps", "the last three steps occur", "last three steps occur in", "three steps occur in the", "steps occur in the mitochondria", "occur in the mitochondria and", "in the mitochondria and involve", "the mitochondria and involve modifications", "mitochondria and involve modifications to", "and involve modifications to the", "involve modifications to the tetrapyrrole", "modifications to the tetrapyrrole side", "to the tetrapyrrole side chains", "the tetrapyrrole side chains and", "tetrapyrrole side chains and finally", "chains and finally insertion", "and finally insertion of", "finally insertion of iron.", "insertion of iron. in addition", "of iron. in addition to", "iron. in addition to these", "in addition to these synthetic", "addition to these synthetic steps", "these synthetic steps a", "synthetic steps a spontaneous", "steps a spontaneous cytosolic", "a spontaneous cytosolic reaction allows", "spontaneous cytosolic reaction allows the", "cytosolic reaction allows the formation", "reaction allows the formation of", "allows the formation of uroporphyringen", "the formation of uroporphyringen i", "formation of uroporphyringen i which", "of uroporphyringen i which is", "uroporphyringen i which is then", "i which is then enzymatically", "which is then enzymatically decarboxylated", "is then enzymatically decarboxylated to", "then enzymatically decarboxylated to coproporphyrinogen", "enzymatically decarboxylated to coproporphyrinogen i", "to coproporphyrinogen i which", "coproporphyrinogen i which cannot", "i which cannot be", "which cannot be metabolized further", "cannot be metabolized further in", "be metabolized further in humans.", "metabolized further in humans. also", "in humans. also lead", "humans. also lead can", "also lead can inactivate", "can inactivate alad the", "inactivate alad the enzyme", "alad the enzyme that", "the enzyme that catalyzes pbg", "enzyme that catalyzes pbg synthesis", "catalyzes pbg synthesis and", "pbg synthesis and ferrochelatase", "and ferrochelatase the enzyme", "ferrochelatase the enzyme that", "the enzyme that catalyzes heme", "enzyme that catalyzes heme synthesis", "catalyzes heme synthesis ponka", "heme synthesis ponka et", "synthesis ponka et al.", "et al. 1999 aijoka", "al. 1999 aijoka et", "1999 aijoka et al.", "aijoka et al. 2006 .

              the", "et al. 2006 .

              the porphyrias", "al. 2006 .

              the porphyrias are", "2006 .

              the porphyrias are disorders", ".

              the porphyrias are disorders that", "porphyrias are disorders that arise", "are disorders that arise from", "disorders that arise from defects", "that arise from defects in", "arise from defects in the", "from defects in the enzymes", "defects in the enzymes of", "in the enzymes of heme", "the enzymes of heme biosynthesis.", "enzymes of heme biosynthesis. defective", "of heme biosynthesis. defective pathway", "heme biosynthesis. defective pathway enzymes", "biosynthesis. defective pathway enzymes after", "defective pathway enzymes after ala", "pathway enzymes after ala synthase", "enzymes after ala synthase result", "after ala synthase result in", "ala synthase result in accumulated", "synthase result in accumulated substrates", "result in accumulated substrates which", "in accumulated substrates which can", "accumulated substrates which can cause", "substrates which can cause either", "which can cause either skin", "can cause either skin problems", "either skin problems neurological", "skin problems neurological complications", "neurological complications or both", "complications or both due", "or both due to their", "both due to their toxicity", "due to their toxicity in", "to their toxicity in higher", "their toxicity in higher concentrations.", "toxicity in higher concentrations. they", "in higher concentrations. they are", "higher concentrations. they are broadly", "concentrations. they are broadly classified", "they are broadly classified as", "are broadly classified as hepatic", "broadly classified as hepatic porphyrias", "classified as hepatic porphyrias or", "as hepatic porphyrias or erythropoietic", "hepatic porphyrias or erythropoietic porphyrias", "or erythropoietic porphyrias based", "erythropoietic porphyrias based on", "porphyrias based on the", "based on the site of", "on the site of the", "the site of the overproduction", "site of the overproduction of", "of the overproduction of the", "the overproduction of the substrate.", "overproduction of the substrate. each", "of the substrate. each defect", "the substrate. each defect is", "substrate. each defect is described", "each defect is described together", "defect is described together with", "is described together with the", "described together with the reaction", "together with the reaction it", "with the reaction it affects", "reaction it affects peoc'h", "it affects peoc'h et", "affects peoc'h et al.", "peoc'h et al. 2016 ." ] }, { "record_id": "GLY_000594_1_1292", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "189483", "r hsa", "hsa 189483", "r hsa 189483" ] }, { "record_id": "GLY_000594_1_1292", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "heme degradation", "most of", "of the", "the heme", "heme degraded", "degraded in", "in humans", "humans comes", "comes from", "from hemoglobin.", "hemoglobin. approximately", "approximately 6", "6 8", "8 grams", "grams of", "of hemoglobin", "hemoglobin is", "is degraded", "degraded daily", "daily which", "which is", "is equivalent", "equivalent to", "to approximately", "approximately 300", "300 milligrams", "milligrams of", "of heme", "heme per", "per day.", "day. heme", "heme is", "is not", "not recycled", "recycled so", "so it", "it must", "must be", "be degraded", "degraded and", "and excreted.", "excreted. the", "the iron", "is conserved.", "conserved. there", "there are", "are two", "two steps", "steps to", "to heme", "degradation
              1.", "
              1. cleavage", "cleavage of", "heme ring", "ring by", "by a", "a microsomal", "microsomal heme", "heme oxygenase", "oxygenase producing", "producing biliverdin
              2.", "biliverdin
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              bilirubin", "bilirubin.
              bilirubin can", "can then", "then be", "be conjugated", "conjugated with", "with glucuronic", "glucuronic acid", "acid and", "most of the", "of the heme", "the heme degraded", "heme degraded in", "degraded in humans", "in humans comes", "humans comes from", "comes from hemoglobin.", "from hemoglobin. approximately", "hemoglobin. approximately 6", "approximately 6 8", "6 8 grams", "8 grams of", "grams of hemoglobin", "of hemoglobin is", "hemoglobin is degraded", "is degraded daily", "degraded daily which", "daily which is", "which is equivalent", "is equivalent to", "equivalent to approximately", "to approximately 300", "approximately 300 milligrams", "300 milligrams of", "milligrams of heme", "of heme per", "heme per day.", "per day. heme", "day. heme is", "heme is not", "is not recycled", "not recycled so", "recycled so it", "so it must", "it must be", "must be degraded", "be degraded and", "degraded and excreted.", "and excreted. the", "excreted. the iron", "iron however", "however is", "is conserved. there", "conserved. there are", "there are two", "are two steps", "two steps to", "steps to heme", "to heme degradation", "heme degradation
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              1. cleavage of", "cleavage of the", "the heme ring", "heme ring by", "ring by a", "by a microsomal", "a microsomal heme", "microsomal heme oxygenase", "heme oxygenase producing", "oxygenase producing biliverdin
              2.", "producing biliverdin
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              2. biliverdin is", "biliverdin is reduced", "is reduced to", "reduced to bilirubin.
              bilirubin", "to bilirubin.
              bilirubin can", "bilirubin.
              bilirubin can then", "can then be", "then be conjugated", "be conjugated with", "conjugated with glucuronic", "with glucuronic acid", "glucuronic acid and", "acid and excreted.", "most of the heme", "of the heme degraded", "the heme degraded in", "heme degraded in humans", "degraded in humans comes", "in humans comes from", "humans comes from hemoglobin.", "comes from hemoglobin. approximately", "from hemoglobin. approximately 6", "hemoglobin. approximately 6 8", "approximately 6 8 grams", "6 8 grams of", "8 grams of hemoglobin", "grams of hemoglobin is", "of hemoglobin is degraded", "hemoglobin is degraded daily", "is degraded daily which", "degraded daily which is", "daily which is equivalent", "which is equivalent to", "is equivalent to approximately", "equivalent to approximately 300", "to approximately 300 milligrams", "approximately 300 milligrams of", "300 milligrams of heme", "milligrams of heme per", "of heme per day.", "heme per day. heme", "per day. heme is", "day. heme is not", "heme is not recycled", "is not recycled so", "not recycled so it", "recycled so it must", "so it must be", "it must be degraded", "must be degraded and", "be degraded and excreted.", "degraded and excreted. the", "and excreted. the iron", "the iron however", "however is conserved.", "is conserved. there are", "conserved. there are two", "there are two steps", "are two steps to", "two steps to heme", "steps to heme degradation", "to heme degradation
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              1. cleavage of the", "cleavage of the heme", "of the heme ring", "the heme ring by", "heme ring by a", "ring by a microsomal", "by a microsomal heme", "a microsomal heme oxygenase", "microsomal heme oxygenase producing", "heme oxygenase producing biliverdin
              2.", "oxygenase producing biliverdin
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              bilirubin", "reduced to bilirubin.
              bilirubin can", "to bilirubin.
              bilirubin can then", "bilirubin.
              bilirubin can then be", "can then be conjugated", "then be conjugated with", "be conjugated with glucuronic", "conjugated with glucuronic acid", "with glucuronic acid and", "glucuronic acid and excreted.", "most of the heme degraded", "of the heme degraded in", "the heme degraded in humans", "heme degraded in humans comes", "degraded in humans comes from", "in humans comes from hemoglobin.", "humans comes from hemoglobin. approximately", "comes from hemoglobin. approximately 6", "from hemoglobin. approximately 6 8", "hemoglobin. approximately 6 8 grams", "approximately 6 8 grams of", "6 8 grams of hemoglobin", "8 grams of hemoglobin is", "grams of hemoglobin is degraded", "of hemoglobin is degraded daily", "hemoglobin is degraded daily which", "is degraded daily which is", "degraded daily which is equivalent", "daily which is equivalent to", "which is equivalent to approximately", "is equivalent to approximately 300", "equivalent to approximately 300 milligrams", "to approximately 300 milligrams of", "approximately 300 milligrams of heme", "300 milligrams of heme per", "milligrams of heme per day.", "of heme per day. heme", "heme per day. heme is", "per day. heme is not", "day. heme is not recycled", "heme is not recycled so", "is not recycled so it", "not recycled so it must", "recycled so it must be", "so it must be degraded", "it must be degraded and", "must be degraded and excreted.", "be degraded and excreted. the", "degraded and excreted. the iron", "excreted. the iron however", "iron however is", "however is conserved. there", "is conserved. there are two", "conserved. there are two steps", "there are two steps to", "are two steps to heme", "two steps to heme degradation", "steps to heme degradation
              1.", "to heme degradation
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              1. cleavage of the heme", "cleavage of the heme ring", "of the heme ring by", "the heme ring by a", "heme ring by a microsomal", "ring by a microsomal heme", "by a microsomal heme oxygenase", "a microsomal heme oxygenase producing", "microsomal heme oxygenase producing biliverdin
              2.", "heme oxygenase producing biliverdin
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              2. biliverdin is reduced to", "biliverdin is reduced to bilirubin.
              bilirubin", "is reduced to bilirubin.
              bilirubin can", "reduced to bilirubin.
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is", "synthesis is downregulated", "is downregulated in", "downregulated in influenza", "in influenza virus", "influenza virus infection", "virus infection through", "infection through still", "through still uncharacterized", "still uncharacterized mechanisms", "mechanisms katze", "katze 1986", "1986 garfinkel", "garfinkel 1992", "1992 kash", ". in", "in most human", "most human influenza", "human influenza a", "influenza a strains", "strains such", "such as pr8", "the pb1 mrna", "pb1 mrna segment", "mrna segment is", "segment is capable", "is capable of", "capable of producing", "of producing a", "producing a second", "a second protein", "protein pb1", "f2 from", "from a short", "a short +1", "short +1 open", "+1 open reading", "open reading frame", "reading frame initiating", "frame initiating downstream", "initiating downstream of", "downstream of the", "of the pb1", "the pb1 orf", "pb1 orf initiation", "orf initiation codon", "codon chen", "chen 2001", "spliced and unspliced viral", "and unspliced viral mrna", "unspliced viral mrna in", "viral mrna in the", "mrna in the cytoplasm", "in the cytoplasm are", "the cytoplasm are translated", "cytoplasm are translated by", "are translated by host", "translated by host cell", "by host cell ribosomal", "host cell ribosomal translation", "cell ribosomal translation machinery", "translation machinery reviewed", "machinery reviewed in", "in kash 2006", "kash 2006 .", "2006 . at", ". at least", "at least ten viral", "least ten viral proteins", "ten viral proteins are", "viral proteins are synthesized:", "are synthesized: ha", "m1 and m2.", "and m2. viral", "m2. viral mrna", "viral mrna translation is", "mrna translation is believed", "translation is believed to", "is believed to be", "believed to be enhanced", "to be enhanced by", "be enhanced by conserved", "enhanced by conserved 5'utr", "by conserved 5'utr sequences", "conserved 5'utr sequences that", "5'utr sequences that interact", "sequences that interact with", "that interact with the", "interact with the ribosomal", "with the ribosomal machinery", "the ribosomal machinery and", "ribosomal machinery and at", "machinery and at least", "and at least one", "at least one cellular", "least one cellular rna", "one cellular rna binding", "cellular rna binding protein", "binding protein g", "protein g rich", "g rich sequence factor", "rich sequence factor 1", "factor 1 grsf", "1 grsf 1", "1 has", "has been found to", "been found to specifically", "found to specifically interact", "to specifically interact with", "specifically interact with the", "interact with the viral", "with the viral 5'", "the viral 5' utrs.", "utrs. park", "park 1999 .", "1999 . the", ". the viral", "the viral ns1 protein", "viral ns1 protein and", "ns1 protein and the", "protein and the cellular", "and the cellular protein", "the cellular protein p58", "cellular protein p58 ipk", "p58 ipk enhance", "ipk enhance viral", "enhance viral translation indirectly", "viral translation indirectly by", "translation indirectly by preventing", "indirectly by preventing the", "by preventing the activation", "preventing the activation of", "the activation of the", "activation of the translational", "of the translational inhibitor", "the translational inhibitor pkr", "inhibitor pkr salvatore", "2002 goodman", "goodman 2006 .", "2006 . the", "viral ns1 protein has", "ns1 protein has also", "protein has also been", "has also been proposed", "also been proposed to", "been proposed to specifically", "proposed to specifically enhance", "to specifically enhance translation", "specifically enhance translation through", "enhance translation through interaction", "translation through interaction with", "through interaction with host", "interaction with host poly", "with host poly a", "poly a binding", "a binding protein", "protein 1 pabp1", "pabp1 burgui", "burgui 2003 .", "2003 . simultaneously", "simultaneously host cell", "host cell protein synthesis", "cell protein synthesis is", "protein synthesis is downregulated", "synthesis is downregulated in", "is downregulated in influenza", "downregulated in influenza virus", "in influenza virus infection", "influenza virus infection through", "virus infection through still", "infection through still uncharacterized", "through still uncharacterized mechanisms", "uncharacterized mechanisms katze", "2006 . in", ". in most", "in most human influenza", "most human influenza a", "human influenza a strains", "a strains such", "strains such as", "pr8 the", "the pb1 mrna segment", "pb1 mrna segment is", "mrna segment is capable", "segment is capable of", "is capable of producing", "capable of producing a", "of producing a second", "producing a second protein", "second protein pb1", "protein pb1 f2", "pb1 f2 from", "f2 from a", "from a short +1", "a short +1 open", "short +1 open reading", "+1 open reading frame", "open reading frame initiating", "reading frame initiating downstream", "frame initiating downstream of", "initiating downstream of the", "downstream of the pb1", "of the pb1 orf", "the pb1 orf initiation", "pb1 orf initiation codon", "initiation codon chen", "chen 2001 .", "spliced and unspliced viral mrna", "and unspliced viral mrna in", "unspliced viral mrna in the", "viral mrna in the cytoplasm", "mrna in the cytoplasm are", "in the cytoplasm are translated", "the cytoplasm are translated by", "cytoplasm are translated by host", "are translated by host cell", "translated by host cell ribosomal", "by host cell ribosomal translation", "host cell ribosomal translation machinery", "ribosomal translation machinery reviewed", "translation machinery reviewed in", "machinery reviewed in kash", "reviewed in kash 2006", "in kash 2006 .", "2006 . at least", ". at least ten", "at least ten viral proteins", "least ten viral proteins are", "ten viral proteins are synthesized:", "proteins are synthesized: ha", "synthesized: ha na", "ha na pb1", "na pb1 pb2", "pb1 pb2 pa", "pb2 pa np", "pa np ns1", "np ns1 nep/ns2", "ns1 nep/ns2 m1", "nep/ns2 m1 and", "and m2. viral mrna", "m2. viral mrna translation", "viral mrna translation is believed", "mrna translation is believed to", "translation is believed to be", "is believed to be enhanced", "believed to be enhanced by", "to be enhanced by conserved", "be enhanced by conserved 5'utr", "enhanced by conserved 5'utr sequences", "by conserved 5'utr sequences that", "conserved 5'utr sequences that interact", "5'utr sequences that interact with", "sequences that interact with the", "that interact with the ribosomal", "interact with the ribosomal machinery", "with the ribosomal machinery and", "the ribosomal machinery and at", "ribosomal machinery and at least", "machinery and at least one", "and at least one cellular", "at least one cellular rna", "least one cellular rna binding", "one cellular rna binding protein", "rna binding protein g", "binding protein g rich", "protein g rich sequence", "g rich sequence factor 1", "sequence factor 1 grsf", "factor 1 grsf 1", "grsf 1 has", "1 has been", "has been found to specifically", "been found to specifically interact", "found to specifically interact with", "to specifically interact with the", "specifically interact with the viral", "interact with the viral 5'", "with the viral 5' utrs.", "5' utrs. park", "park 1995 park", "1995 park 1999", "1999 . the viral", ". the viral ns1", "the viral ns1 protein and", "viral ns1 protein and the", "ns1 protein and the cellular", "protein and the cellular protein", "and the cellular protein p58", "the cellular protein p58 ipk", "protein p58 ipk enhance", "p58 ipk enhance viral", "ipk enhance viral translation", "enhance viral translation indirectly by", "viral translation indirectly by preventing", "translation indirectly by preventing the", "indirectly by preventing the activation", "by preventing the activation of", "preventing the activation of the", "the activation of the translational", "activation of the translational inhibitor", "of the translational inhibitor pkr", "translational inhibitor pkr salvatore", "pkr salvatore 2002", "2006 . the viral", "the viral ns1 protein has", "viral ns1 protein has also", "ns1 protein has also been", "protein has also been proposed", "has also been proposed to", "also been proposed to specifically", "been proposed to specifically enhance", "proposed to specifically enhance translation", "to specifically enhance translation through", "specifically enhance translation through interaction", "enhance translation through interaction with", "translation through interaction with host", "through interaction with host poly", "interaction with host poly a", "host poly a binding", "poly a binding protein", "a binding protein 1", "binding protein 1 pabp1", ". simultaneously host", "simultaneously host cell protein", "host cell protein synthesis is", "cell protein synthesis is downregulated", "protein synthesis is downregulated in", "synthesis is downregulated in influenza", "is downregulated in influenza virus", "downregulated in influenza virus infection", "in influenza virus infection through", "influenza virus infection through still", "virus infection through still uncharacterized", "infection through still uncharacterized mechanisms", "still uncharacterized mechanisms katze", "mechanisms katze 1986", "katze 1986 garfinkel", "1986 garfinkel 1992", "garfinkel 1992 kash", "1992 kash 2006", "2006 . in most", ". in most human", "in most human influenza a", "most human influenza a strains", "influenza a strains such", "a strains such as", "strains such as pr8", "as pr8 the", "pr8 the pb1", "the pb1 mrna segment is", "pb1 mrna segment is capable", "mrna segment is capable of", "segment is capable of producing", "is capable of producing a", "capable of producing a second", "of producing a second protein", "a second protein pb1", "second protein pb1 f2", "pb1 f2 from a", "f2 from a short", "from a short +1 open", "a short +1 open reading", "short +1 open reading frame", "+1 open reading frame initiating", "open reading frame initiating downstream", "reading frame initiating downstream of", "frame initiating downstream of the", "initiating downstream of the pb1", "downstream of the pb1 orf", "of the pb1 orf initiation", "the pb1 orf initiation codon", "orf initiation codon chen", "codon chen 2001" ] }, { "record_id": "GLY_000594_1_1301", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "193634", "r hsa", "hsa 193634", "r hsa 193634" ] }, { "record_id": "GLY_000594_1_1301", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "axonal growth", "growth inhibition", "rhoa activation", "axonal growth inhibition", "inhibition rhoa", "growth inhibition rhoa", "inhibition rhoa activation", "axonal growth inhibition rhoa", "growth inhibition rhoa activation", "p75ntr can", "can also", "also form", "form a", "a receptor", "receptor complex", "complex with", "with the", "the nogo", "nogo receptor", "ngr .", ". such", "such complexes", "complexes mediates", "mediates axonal", "axonal outgrowth", "outgrowth inhibitory", "inhibitory signals", "signals of", "of mdgis", "myelin derived", "derived growth", "growth inhibitors", "such as", "as nogo66", "myelin associated", "associated glycoprotein", "and oligodendrocyte", "oligodendrocyte myelin", "myelin glycoprotein", "omgp .", "p75ntr can also", "can also form", "also form a", "form a receptor", "a receptor complex", "receptor complex with", "complex with the", "with the nogo", "the nogo receptor", "receptor ngr", "ngr . such", ". such complexes", "such complexes mediates", "complexes mediates axonal", "mediates axonal outgrowth", "axonal outgrowth inhibitory", "outgrowth inhibitory signals", "inhibitory signals of", "signals of mdgis", "mdgis myelin", "myelin derived growth", "derived growth inhibitors", "such as nogo66", "nogo66 myelin", "myelin associated glycoprotein", "glycoprotein mag", "and oligodendrocyte myelin", "oligodendrocyte myelin glycoprotein", "glycoprotein omgp", "p75ntr can also form", "can also form a", "also form a receptor", "form a receptor complex", "a receptor complex with", "receptor complex with the", "complex with the nogo", "with the nogo receptor", "nogo receptor ngr", "receptor ngr .", "ngr . such complexes", ". such complexes mediates", "such complexes mediates axonal", "complexes mediates axonal outgrowth", "mediates axonal outgrowth inhibitory", "axonal outgrowth inhibitory signals", "outgrowth inhibitory signals of", "inhibitory signals of mdgis", "of mdgis myelin", "mdgis myelin derived", "myelin derived growth inhibitors", "inhibitors such", "as nogo66 myelin", "nogo66 myelin associated", "associated glycoprotein mag", "mag and", "and oligodendrocyte myelin glycoprotein", "myelin glycoprotein omgp", "glycoprotein omgp .", "p75ntr can also form a", "can also form a receptor", "also form a receptor complex", "form a receptor complex with", "a receptor complex with the", "receptor complex with the nogo", "complex with the nogo receptor", "the nogo receptor ngr", "nogo receptor ngr .", "receptor ngr . such", "ngr . such complexes mediates", ". such complexes mediates axonal", "such complexes mediates axonal outgrowth", "complexes mediates axonal outgrowth inhibitory", "mediates axonal outgrowth inhibitory signals", "axonal outgrowth inhibitory signals of", "outgrowth inhibitory signals of mdgis", "signals of mdgis myelin", "of mdgis myelin derived", "mdgis myelin derived growth", "growth inhibitors such", "inhibitors such as", "such as nogo66 myelin", "as nogo66 myelin associated", "nogo66 myelin associated glycoprotein", "myelin associated glycoprotein mag", "mag and oligodendrocyte", "oligodendrocyte myelin glycoprotein omgp", "myelin glycoprotein omgp ." ] }, { "record_id": "GLY_000594_1_1302", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "193692", "r hsa", "hsa 193692", "r hsa 193692" ] }, { "record_id": "GLY_000594_1_1302", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulated proteolysis", "proteolysis of", "of p75ntr", "regulated proteolysis of", "proteolysis of p75ntr", "regulated proteolysis of p75ntr", "p75ntr undergoes", "undergoes a", "a process", "process of", "of regulated", "regulated intramembrane", "intramembrane proteolysis", "similar to", "to other", "other transmembrane", "transmembrane proteins", "proteins such", "such as", "as notch", "beta amyloid", "amyloid precursor", "precursor protein", "and erbb4.", "erbb4. each", "each of", "of these", "these proteins", "proteins is", "is subjected", "to two", "two sequential", "sequential cleavages.", "cleavages. the", "the first", "first one", "one occurs", "occurs in", "in the", "the extracellular", "extracellular part", "part of", "of the", "the protein", "protein and", "and is", "is mediated", "mediated by", "by the", "the 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amplifications have been", "amplifications have been identified", "have been identified in", "been identified in 10%", "identified in 10% of", "in 10% of gastric", "10% of gastric cancers", "gastric cancers where", "cancers where they", "where they are associated", "they are associated with", "are associated with poor", "associated with poor prognosis", "with poor prognosis diffuse", "poor prognosis diffuse cancers", "diffuse cancers hattori", "and in ~1% of", "in ~1% of breast", "~1% of breast cancers", "breast cancers turner", "tannheimer 2000 .", ". fgfr2", "fgfr2 amplification often occur", "amplification often occur in", "often occur in conjunction", "occur in conjunction with", "in conjunction with deletions", "conjunction with deletions of", "with deletions of c", "deletions of c terminal", "of c terminal exons", "terminal exons resulting", "exons resulting in", "resulting in expression of", "in expression of a", "expression of a internalization", "a internalization and", "internalization and degradation", "and degradation resistant form", "degradation resistant form of", "resistant form of the", "form of the receptor", "the receptor takeda", "2008 2009 .", "2009 . amplification affects", ". amplification affects signaling", "amplification affects signaling without", "affects signaling without altering", "signaling without altering the", "without altering the intrinsic", "altering the intrinsic kinase", "the intrinsic kinase activity", "intrinsic kinase activity of", "kinase activity of the", "activity of the receptor.", "of the receptor. signaling", "the receptor. signaling through", "receptor. signaling through overexpressed", "signaling through overexpressed fgfr2", "through overexpressed fgfr2 also", "overexpressed fgfr2 also shows", "fgfr2 also shows evidence", "also shows evidence of", "shows evidence of being", "evidence of being ligand", "of being ligand independent", "being ligand independent and", "ligand independent and sensitive", "independent and sensitive to", "and sensitive to fgfr", "sensitive to fgfr inhibitors", "inhibitors lorenzi", "cha 2009 .", "fgfr2 amplifications have been identified", "amplifications have been identified in", "have been identified in 10%", "been identified in 10% of", "identified in 10% of gastric", "in 10% of gastric cancers", "of gastric cancers where", "gastric cancers where they", "cancers where they are", "where they are associated with", "they are associated with poor", "are associated with poor prognosis", "associated with poor prognosis diffuse", "with poor prognosis diffuse cancers", "prognosis diffuse cancers hattori", "cancers hattori 1996", "hattori 1996 ueda", "1996 ueda 1999", "ueda 1999 shin", "1999 shin 2000", "shin 2000 kunii", "2000 kunii 2008", "2008 and", "and in ~1% of breast", "in ~1% of breast cancers", "of breast cancers turner", "cancers turner 2010", "turner 2010 tannheimer", "2010 tannheimer 2000", "2000 . fgfr2", ". fgfr2 amplification", "fgfr2 amplification often occur in", "amplification often occur in conjunction", "often occur in conjunction with", "occur in conjunction with deletions", "in conjunction with deletions of", "conjunction with deletions of c", "with deletions of c terminal", "deletions of c terminal exons", "c terminal exons resulting", "terminal exons resulting in", "exons resulting in expression", "resulting in expression of a", "in expression of a internalization", "of a internalization and", "a internalization and degradation", "internalization and degradation resistant", "and degradation resistant form of", "degradation resistant form of the", "resistant form of the receptor", "of the receptor takeda", "receptor takeda 1999", "takeda 1999 cha", "1999 cha 2008", "cha 2008 2009", "2008 2009 . amplification", "2009 . amplification affects signaling", ". amplification affects signaling without", "amplification affects signaling without altering", "affects signaling without altering the", "signaling without 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"human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "202670", "r hsa", "hsa 202670", "r hsa 202670" ] }, { "record_id": "GLY_000594_1_1307", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "erks are", "are inactivated", "erks are inactivated", "map kinases", "kinases are", "inactivated by", "by a", "a family", "family of", "of protein", "protein named", "named map", "map kinase", "kinase phosphatases", "mkps .", ". they", "they act", "act through", "through dephosphorylation", "dephosphorylation of", "of threonine", "threonine and/or", "and/or tyrosine", "tyrosine residues", "residues within", "within the", "the signature", "signature sequence", "located in", "in the", "the activation", "activation loop", "loop of", "of map", "pt=phosphothreonine and", "and py=phosphotyrosine", "py=phosphotyrosine .", ". mkps", "mkps are", "are divided", "divided into", "into three", "three major", "major categories", 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              there", "unavoidable.

              there are", "are 57", "57 human", "human cyps", "in 18", "18 families", "families and", "and 42", "42 subfamilies", "mostly concentrated", "the endoplasmic", "endoplasmic reticulum", "reticulum of", "of liver", "liver cells", "cells although", "although many", "many tissues", "tissues have", "have them", "them to", "to some", "some extent", "nelson dr", "dr et", "et al", "2004 .", ". cyps", "cyps are", "are grouped", "grouped into", "into 14", "14 families", "families according", "according to", "to their", "their sequence", "sequence similarity.", "similarity. generally", "enzymes in", "the same", "same family", "family share", "share 40%", "40% sequence", "sequence similarity", "similarity and", "and 55%", "55% within", "within a", "a subfamily.", "subfamily. nomenclature", "nomenclature of", "of p450s", "p450s is", "is as", "as follows.", "follows. cyp", "to represent", "represent cytochrome", "p450 superfamily", "followed by", "by an", "an arabic", "arabic number", "number for", "for the", "the family", "a capital", "capital letter", "letter for", "the subfamily", "subfamily and", "and finally", "finally a", "a second", "second arabic", "number to", "to denote", "denote the", "the isoenzyme.", "isoenzyme. an", "an example", "example is", "is cyp1a1", "cyp1a1 which", "which is", "the first", "first enzyme", "enzyme in", "in subfamily", "subfamily a", "a of", "of cytochrome", "p450 family", "family 1.

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              ", "

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              ", "

              rh", "rh substrate", "substrate +", "+ o2 +", "o2 + nadph", "+ nadph +", "nadph + h+", "+ h+ =", "h+ = roh", "roh product", "product +", "+ h2o +", "h2o + nadp+

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              the", "anaerobic conditions.

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              the metabolites produced", "metabolites produced from", "produced from these", "from these reactions", "these reactions can", "reactions can either", "can either be", "either be mere", "be mere intermediates", "mere intermediates which", "intermediates which have", "which have relatively", "have relatively little", "relatively little reactivity", "little reactivity towards", "reactivity towards cellular", "towards cellular sysytems", "cellular sysytems and", "sysytems and are", "and are readily", "are readily conjugated", "conjugated or", "or they", "can be disruptive", "be disruptive to", "disruptive to cellular", "to cellular systems.", "cellular systems. indeed", "indeed inert", "inert compounds need", "compounds need to", "need to be", "to be prepared", "be prepared for", "prepared for conjugation", "for conjugation and", "conjugation and thus", "and thus the", "thus the formation", "the formation of", "formation of potentially", "of potentially reactive", "potentially reactive metabolites", "reactive metabolites is", "metabolites is in", "is in most", "in most cases", "most cases unavoidable.

              there", "cases unavoidable.

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              there are 57", "are 57 human", "57 human cyps", "cyps in", "in 18 families", "18 families and", "families and 42", "and 42 subfamilies", "mostly concentrated in", "in the endoplasmic", "the endoplasmic reticulum", "endoplasmic reticulum of", "reticulum of liver", "of liver cells", "liver cells although", "cells although many", "although many tissues", "many tissues have", "tissues have them", "have them to", "them to some", "to some extent", "extent nelson", "nelson dr et", "dr et al", "al 2004", "2004 . cyps", ". cyps are", "cyps are grouped", "are grouped into", "grouped into 14", "into 14 families", "14 families according", "families according to", "according to their", "to their sequence", "their sequence similarity.", "sequence similarity. generally", "generally enzymes", "enzymes in the", "in the same", "the same family", "same family share", "family share 40%", "share 40% sequence", "40% sequence similarity", "sequence similarity and", "similarity and 55%", "and 55% within", "55% within a", "within a subfamily.", "a subfamily. nomenclature", "subfamily. nomenclature of", "nomenclature of p450s", "of p450s is", "p450s is as", "is as follows.", "as follows. cyp", "cyp to", "to represent cytochrome", "represent cytochrome p450", "cytochrome p450 superfamily", "followed by an", "by an arabic", "an arabic number", "arabic number for", "number for the", "for the family", "family a", "a capital letter", "capital letter for", "letter for the", "for the subfamily", "the subfamily and", "subfamily and finally", "and finally a", "finally a second", "a second arabic", "second arabic number", "arabic number to", "number to denote", "to denote the", "denote the isoenzyme.", "the isoenzyme. an", "isoenzyme. an example", "an example is", "example is cyp1a1", "is cyp1a1 which", "cyp1a1 which is", "which is the", "is the first", "the first enzyme", "first enzyme in", "enzyme in subfamily", "in subfamily a", "subfamily a of", "a of cytochrome", "of cytochrome p450", "cytochrome p450 family", "p450 family 1.

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              ", "process.

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              ", "water.

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              ", "

              the p450 isozyme system", "p450 isozyme system is", "isozyme system is the", "system is the major", "is the major phase", "the major phase 1", "major phase 1 biotransforming", "phase 1 biotransforming system", "1 biotransforming system in", "biotransforming system in man", "in man accounting", "man accounting for", "accounting for more than", "for more than 90%", "more than 90% of", "than 90% of drug", "90% of drug biotransformations.", "of drug biotransformations. this", "drug biotransformations. this system", "biotransformations. this system has", "this system has huge", "system has huge catalytic", "has huge catalytic versatility", "huge catalytic versatility and", "catalytic versatility and a", "versatility and a broad", "and a broad substrate", "a broad substrate specificity", "substrate specificity acting", "specificity acting upon", "acting upon xenobiotica and", "upon xenobiotica and endogenous", "xenobiotica and endogenous compounds.", "and endogenous compounds. it", "endogenous compounds. it is", "compounds. it is also", "it is also called", "is also called the", "also called the mixed", "called the mixed function", "the mixed function oxidase", "mixed function oxidase system", "system the", "the p450 monooxygenases and", "p450 monooxygenases and the", "monooxygenases and the heme", "and the heme thiolate", "the heme thiolate protein", "heme thiolate protein system.", "thiolate protein system. all", "protein system. all p450", "system. all p450 enzymes", "all p450 enzymes are", "p450 enzymes are a", "enzymes are a group", "are a group of", "a group of heme", "group of heme containing", "of heme containing isozymes", "heme containing isozymes which", "containing isozymes which are", "isozymes which are located", "which are located on", "are located on the", "located on the membrane", "on the membrane of", "the membrane of the", "membrane of the smooth", "of the smooth endoplasmic", "the smooth endoplasmic reticulum.", "smooth endoplasmic reticulum. they", "endoplasmic reticulum. they can", "reticulum. they can be", "they can be found", "can be found in", "be found in all", "found in all tissues", "in all tissues of", "all tissues of the", "tissues of the human", "of the human body", "the human body but", "human body but are", "body but are most", "but are most concentrated", "are most concentrated in", "most concentrated in the", "concentrated in the liver.", "in the liver. the", "the liver. the name", "liver. the name \\cytochrome", "the name \\cytochrome p450\\", "\\cytochrome p450\\ cyp", "cyp is derived", "is derived from the", "derived from the spectral", "from the spectral absorbance", "the spectral absorbance maximum", "spectral absorbance maximum at", "absorbance maximum at 450nm", "maximum at 450nm when", "at 450nm when carbon", "450nm when carbon monoxide", "when carbon monoxide binds", "carbon monoxide binds to", "monoxide binds to cyp", "binds to cyp in", "to cyp in its", "cyp in its reduced", "its reduced ferrous", "fe2+ state. the", "state. the basic reaction", "the basic reaction catalyzed", "basic reaction catalyzed by", "reaction catalyzed by cyp", "catalyzed by cyp is", "by cyp is mono", "cyp is mono oxygenation", "mono oxygenation that", "oxygenation that is", "that is the transfer", "is the transfer of", "the transfer of one", "transfer of one oxygen", "of one oxygen atom", "one oxygen atom from", "oxygen atom from molecular", "atom from molecular oxygen", "from molecular oxygen to", "molecular oxygen to a", "oxygen to a substrate.", "to a substrate. the", "a substrate. the other", "substrate. the other oxygen", "the other oxygen atom", "other oxygen atom is", "oxygen atom is reduced", "atom is reduced to", "is reduced to water", "reduced to water during", "to water during the", "water during the reaction", "during the reaction with", "the reaction with the", "reaction with the equivalents", "with the equivalents coming", "the equivalents coming from", "equivalents coming from the", "coming from the cofactor", "from the cofactor nadph.", "the cofactor nadph. the", "cofactor nadph. the basic", "nadph. the basic reaction", "the basic reaction is", "basic reaction is

              ", "is

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              the", "h2o + nadp+

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              the", "under anaerobic conditions.

              the metabolites", "anaerobic conditions.

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              there", "most cases unavoidable.

              there are", "cases unavoidable.

              there are 57", "unavoidable.

              there are 57 human", "are 57 human cyps", "human cyps in", "cyps in 18", "in 18 families and", "18 families and 42", "families and 42 subfamilies", "subfamilies mostly", "mostly concentrated in the", "concentrated in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum of", "endoplasmic reticulum of liver", "reticulum of liver cells", "of liver cells although", "liver cells although many", "cells although many tissues", "although many tissues have", "many tissues have them", "tissues have them to", "have them to some", "them to some extent", "some extent nelson", "extent nelson dr", "nelson dr et al", "et al 2004", "al 2004 .", "2004 . cyps are", ". cyps are grouped", "cyps are grouped into", "are grouped into 14", "grouped into 14 families", "into 14 families according", "14 families according to", "families according to their", "according to their sequence", "to their sequence similarity.", "their sequence similarity. generally", "similarity. generally enzymes", "generally enzymes in", "enzymes in the same", "in the same family", "the same family share", "same family share 40%", "family share 40% sequence", "share 40% sequence similarity", "40% sequence similarity and", "sequence similarity and 55%", "similarity and 55% within", "and 55% within a", "55% within a subfamily.", "within a subfamily. nomenclature", "a subfamily. nomenclature of", "subfamily. nomenclature of p450s", "nomenclature of p450s is", "of p450s is as", "p450s is as follows.", "is as follows. cyp", "follows. cyp to", "cyp to represent", "to represent cytochrome p450", "represent cytochrome p450 superfamily", "superfamily followed", "followed by an arabic", "by an arabic number", "an arabic number for", "arabic number for the", "number for the family", "the family a", "family a capital", "a capital letter for", "capital letter for the", "letter for the subfamily", "for the subfamily and", "the subfamily and finally", "subfamily and finally a", "and finally a second", "finally a second arabic", "a second arabic number", "second arabic number to", "arabic number to denote", "number to denote the", "to denote the isoenzyme.", "denote the isoenzyme. an", "the isoenzyme. an example", "isoenzyme. an example is", "an example is cyp1a1", "example is cyp1a1 which", "is cyp1a1 which is", "cyp1a1 which is the", "which is the first", "is the first enzyme", "the first enzyme in", "first enzyme in subfamily", "enzyme in subfamily a", "in subfamily a of", "subfamily a of cytochrome", "a of cytochrome p450", "of cytochrome p450 family", "cytochrome p450 family 1.

              the", "p450 family 1.

              the majority", "family 1.

              the majority of", "1.

              the majority of the", "majority of the enzymes", "of the enzymes are", "the enzymes are present", "enzymes are present in", "are present in the", "present in the cyp1", "in the cyp1 4", "the cyp1 4 families.", "cyp1 4 families. cyp1", "4 families. cyp1 3", "families. cyp1 3 are", "cyp1 3 are primarily", "3 are primarily concerned", "are primarily concerned with", "primarily concerned with xenobiotic", "concerned with xenobiotic biotransformation", "with xenobiotic biotransformation whereas", "xenobiotic biotransformation whereas the", "biotransformation whereas the other", "whereas the other cyps", "the other cyps deal", "other cyps deal primarily", "cyps deal primarily with", "deal primarily with endogenous", "primarily with endogenous compounds.", "with endogenous compounds. the", "endogenous compounds. the cyp", "compounds. the cyp section", "the cyp section is", "cyp section is structured", "section is structured by", "is structured by the", "structured by the typical", "by the typical substrate", "the typical substrate they", "typical substrate they act", "substrate they act upon.", "they act upon. of", "act upon. of the", "upon. of the 57", "of the 57 human", "the 57 human cyps", "human cyps 7", "cyps 7 encode", "7 encode mitochondrial enzymes", "mitochondrial enzymes all", "enzymes all involved", "all involved in sterol", "involved in sterol biosynthesis.", "in sterol biosynthesis. of", "sterol biosynthesis. of the", "biosynthesis. of the remaining", "of the remaining 50", "the remaining 50 microsomal", "remaining 50 microsomal enzymes", "microsomal enzymes 20", "enzymes 20 act", "20 act upon endogenous", "act upon endogenous compounds", "endogenous compounds 15", "compounds 15 on", "15 on xenobiotics and", "on xenobiotics and 15", "xenobiotics and 15 are", "and 15 are the", "15 are the so", "are the so called", "the so called \\orphan", "so called \\orphan enzymes\\", "called \\orphan enzymes\\ with", "\\orphan enzymes\\ with no", "enzymes\\ with no substrate", "with no substrate identified.

              the", "no substrate identified.

              the p450", "substrate identified.

              the p450 catalytic", "identified.

              the p450 catalytic cycle", "p450 catalytic cycle ", "catalytic cycle picture", "cycle picture ", " picture shows", "picture shows the", " shows the steps", "shows the steps involved", "the steps involved when", "steps involved when a", "involved when a substrate", "when a substrate binds", "a substrate binds to", "substrate binds to the", "binds to the enzyme.

              ", "the enzyme.

              1", "enzyme.

              1 ", "color=red> 1 the", "1 the normal", " the normal state", "the normal state of", "normal state of a", "state of a p450", "of a p450 with", "a p450 with the", "p450 with the iron", "with the iron in", "the iron in its", "iron in its ferric", "its ferric fe3+", "fe3+ state.

              ", "state.

              2 ", "color=red> 2 the", "2 the substrate", " the substrate binds", "the substrate binds to", "the enzyme.

              3", "enzyme.

              3 ", "color=red> 3 the", "3 the enzyme", " the enzyme is", "the enzyme is reduced", "enzyme is reduced to", "is reduced to the", "reduced to the ferrous", "the ferrous fe2+", "fe2+ state by", "state by the addition", "by the addition of", "the addition of an", "addition of an electron", "of an electron from", "an electron from nadph", "electron from nadph cytochrome", "from nadph cytochrome p450", "nadph cytochrome p450 reductase.", "cytochrome p450 reductase. the", "p450 reductase. the bound", "reductase. the bound substrate", "the bound substrate facilitates", "bound substrate facilitates this", "substrate facilitates this process.

              ", "this process.

              4", "process.

              4 5", "color=red> 4 5 ", "4 5 molecular", "5 molecular oxygen", " molecular oxygen binds", "molecular oxygen binds and", "oxygen binds and forms", "binds and forms an", "and forms an fe2+ooh", "forms an fe2+ooh complex", "an fe2+ooh complex with", "fe2+ooh complex with the", "complex with the addition", "with the addition of", "the addition of a", "addition of a proton", "of a proton and", "a proton and a", "proton and a second", "and a second donation", "a second donation of", "second donation of an", "donation of an electron", "an electron from either", "electron from either nadph", "from either nadph cytochrome", "either nadph cytochrome p450", "nadph cytochrome p450 reductase", "cytochrome p450 reductase or", "p450 reductase or cytochrome", "reductase or cytochrome b5.", "or cytochrome b5. a", "cytochrome b5. a second", "b5. a second proton", "a second proton cleaves", "second proton cleaves the", "proton cleaves the fe2+ooh", "cleaves the fe2+ooh complex", "the fe2+ooh complex to", "fe2+ooh complex to form", "complex to form water.

              ", "form water.

              6", "water.

              6 ", "color=red> 6 an", "6 an unstable", "an unstable feo", "unstable feo 3+", "feo 3+ complex donates", "3+ complex donates its", "complex donates its oxygen", "donates its oxygen to", "its oxygen to the", "oxygen to the substrate", "to the substrate ", "substrate 7", " 7 .", "color=red> 7 . the", "7 . the oxidised", ". the oxidised substrate", "the oxidised substrate is", "oxidised substrate is released", "substrate is released and", "is released and the", "released and the enzyme", "and the enzyme returns", "the enzyme returns to", "enzyme returns to its", "returns to its initial", "to its initial state", "its initial state ", "state 1", " 1 .

              ", "

              the p450 isozyme system is", "p450 isozyme system is the", "isozyme system is the major", "system is the major phase", "is the major phase 1", "the major phase 1 biotransforming", "major phase 1 biotransforming system", "phase 1 biotransforming system in", "1 biotransforming system in man", "system in man accounting", "in man accounting for", "man accounting for more", "accounting for more than 90%", "for more than 90% of", "more than 90% of drug", "than 90% of drug biotransformations.", "90% of drug biotransformations. this", "of drug biotransformations. this system", "drug biotransformations. this system has", "biotransformations. this system has huge", "this system has huge catalytic", "system has huge catalytic versatility", "has huge catalytic versatility and", "huge catalytic versatility and a", "catalytic versatility and a broad", "versatility and a broad substrate", "and a broad substrate specificity", "broad substrate specificity acting", "substrate specificity acting upon", "specificity acting upon xenobiotica", "acting upon xenobiotica and endogenous", "upon xenobiotica and endogenous compounds.", "xenobiotica and endogenous compounds. it", "and endogenous compounds. it is", "endogenous compounds. it is also", "compounds. it is also called", "it is also called the", "is also called the mixed", "also called the mixed function", "called the mixed function oxidase", "the mixed function oxidase system", "oxidase system the", "system the p450", "the p450 monooxygenases and the", "p450 monooxygenases and the heme", "monooxygenases and the heme thiolate", "and the heme thiolate protein", "the heme thiolate protein system.", "heme thiolate protein system. all", "thiolate protein system. all p450", "protein system. all p450 enzymes", "system. all p450 enzymes are", "all p450 enzymes are a", "p450 enzymes are a group", "enzymes are a group of", "are a group of heme", "a group of heme containing", "group of heme containing isozymes", "of heme containing isozymes which", "heme containing isozymes which are", "containing isozymes which are located", "isozymes which are located on", "which are located on the", "are located on the membrane", "located on the membrane of", "on the membrane of the", "the membrane of the smooth", "membrane of the smooth endoplasmic", "of the smooth endoplasmic reticulum.", "the smooth endoplasmic reticulum. they", "smooth endoplasmic reticulum. they can", "endoplasmic reticulum. they can be", "reticulum. they can be found", "they can be found in", "can be found in all", "be found in all tissues", "found in all tissues of", "in all tissues of the", "all tissues of the human", "tissues of the human body", "of the human body but", "the human body but are", "human body but are most", "body but are most concentrated", "but are most concentrated in", "are most concentrated in the", "most concentrated in the liver.", "concentrated in the liver. the", "in the liver. the name", "the liver. the name \\cytochrome", "liver. the name \\cytochrome p450\\", "name \\cytochrome p450\\ cyp", "p450\\ cyp is", "cyp is derived from", "is derived from the spectral", "derived from the spectral absorbance", "from the spectral absorbance maximum", "the spectral absorbance maximum at", "spectral absorbance maximum at 450nm", "absorbance maximum at 450nm when", "maximum at 450nm when carbon", "at 450nm when carbon monoxide", "450nm when carbon monoxide binds", "when carbon monoxide binds to", "carbon monoxide binds to cyp", "monoxide binds to cyp in", "binds to cyp in its", "to cyp in its reduced", "in its reduced ferrous", "reduced ferrous fe2+", "ferrous fe2+ state.", "fe2+ state. the basic", "state. the basic reaction catalyzed", "the basic reaction catalyzed by", "basic reaction catalyzed by cyp", "reaction catalyzed by cyp is", "catalyzed by cyp is mono", "by cyp is mono oxygenation", "is mono oxygenation that", "mono oxygenation that is", "oxygenation that is the", "that is the transfer of", "is the transfer of one", "the transfer of one oxygen", "transfer of one oxygen atom", "of one oxygen atom from", "one oxygen atom from molecular", "oxygen atom from molecular oxygen", "atom from molecular oxygen to", "from molecular oxygen to a", "molecular oxygen to a substrate.", "oxygen to a substrate. the", "to a substrate. the other", "a substrate. the other oxygen", "substrate. the other oxygen atom", "the other oxygen atom is", "other oxygen atom is reduced", "oxygen atom is reduced to", "atom is reduced to water", "is reduced to water during", "reduced to water during the", "to water during the reaction", "water during the reaction with", "during the reaction with the", "the reaction with the equivalents", "reaction with the equivalents coming", "with the equivalents coming from", "the equivalents coming from the", "equivalents coming from the cofactor", "coming from the cofactor nadph.", "from the cofactor nadph. the", "the cofactor nadph. the basic", "cofactor nadph. the basic reaction", "nadph. the basic reaction is", "the basic reaction is

              ", "reaction is

              rh", "

              rh substrate", "rh substrate +", "substrate + o2 +", "+ o2 + nadph +", "o2 + nadph + h+", "+ nadph + h+ =", "nadph + h+ = roh", "h+ = roh product", "roh product +", "product + h2o +", "+ h2o + nadp+

              the end", "h2o + nadp+

              the end results", "+ nadp+

              the end results of", "nadp+

              the end results of this", "end results of this reaction", "results of this reaction can", "of this reaction can be", "reaction can be n", "be n hydroxylation", "n hydroxylation epoxidation", "hydroxylation epoxidation heteroatom", "epoxidation heteroatom n", "oxygenation heteroatom n", "cleavage isomerization dehydrogenation", "isomerization dehydrogenation replacement", "dehydrogenation replacement by oxygen", "replacement by oxygen or even", "by oxygen or even reduction", "oxygen or even reduction under", "or even reduction under anaerobic", "even reduction under anaerobic conditions.

              the", "reduction under anaerobic conditions.

              the metabolites", "under anaerobic conditions.

              the metabolites produced", "anaerobic conditions.

              the metabolites produced from", "conditions.

              the metabolites produced from these", "metabolites produced from these reactions", "produced from these reactions can", "from these reactions can either", "these reactions can either be", "reactions can either be mere", "can either be mere intermediates", "either be mere intermediates which", "be mere intermediates which have", "mere intermediates which have relatively", "intermediates which have relatively little", "which have relatively little reactivity", "have relatively little reactivity towards", "relatively little reactivity towards cellular", "little reactivity towards cellular sysytems", "reactivity towards cellular sysytems and", "towards cellular sysytems and are", "cellular sysytems and are readily", "sysytems and are readily conjugated", "are readily conjugated or", "conjugated or they", "or they can be", "they can be disruptive to", "can be disruptive to cellular", "be disruptive to cellular systems.", "disruptive to cellular systems. indeed", "cellular systems. indeed inert", "systems. indeed inert compounds", "indeed inert compounds need", "inert compounds need to be", "compounds need to be prepared", "need to be prepared for", "to be prepared for conjugation", "be prepared for conjugation and", "prepared for conjugation and thus", "for conjugation and thus the", "conjugation and thus the formation", "and thus the formation of", "thus the formation of potentially", "the formation of potentially reactive", "formation of potentially reactive metabolites", "of potentially reactive metabolites is", "potentially reactive metabolites is in", "reactive metabolites is in most", "metabolites is in most cases", "is in most cases unavoidable.

              there", "in most cases unavoidable.

              there are", "most cases unavoidable.

              there are 57", "cases unavoidable.

              there are 57 human", "unavoidable.

              there are 57 human cyps", "57 human cyps in", "human cyps in 18", "cyps in 18 families", "in 18 families and 42", "18 families and 42 subfamilies", "42 subfamilies mostly", "subfamilies mostly concentrated", "mostly concentrated in the endoplasmic", "concentrated in the endoplasmic reticulum", "in the endoplasmic reticulum of", "the endoplasmic reticulum of liver", "endoplasmic reticulum of liver cells", "reticulum of liver cells although", "of liver cells although many", "liver cells although many tissues", "cells although many tissues have", "although many tissues have them", "many tissues have them to", "tissues have them to some", "have them to some extent", "to some extent nelson", "some extent nelson dr", "extent nelson dr et", "dr et al 2004", "et al 2004 .", "al 2004 . cyps", "2004 . cyps are grouped", ". cyps are grouped into", "cyps are grouped into 14", "are grouped into 14 families", "grouped into 14 families according", "into 14 families according to", "14 families according to their", "families according to their sequence", "according to their sequence similarity.", "to their sequence similarity. generally", "sequence similarity. generally enzymes", "similarity. generally enzymes in", "generally enzymes in the", "enzymes in the same family", "in the same family share", "the same family share 40%", "same family share 40% sequence", "family share 40% sequence similarity", "share 40% sequence similarity and", "40% sequence similarity and 55%", "sequence similarity and 55% within", "similarity and 55% within a", "and 55% within a subfamily.", "55% within a subfamily. nomenclature", "within a subfamily. nomenclature of", "a subfamily. nomenclature of p450s", "subfamily. nomenclature of p450s is", "nomenclature of p450s is as", "of p450s is as follows.", "p450s is as follows. cyp", "as follows. cyp to", "follows. cyp to represent", "cyp to represent cytochrome", "to represent cytochrome p450 superfamily", "p450 superfamily followed", "superfamily followed by", "followed by an arabic number", "by an arabic number for", "an arabic number for the", "arabic number for the family", "for the family a", "the family a capital", "family a capital letter", "a capital letter for the", "capital letter for the subfamily", "letter for the subfamily and", "for the subfamily and finally", "the subfamily and finally a", "subfamily and finally a second", "and finally a second arabic", "finally a second arabic number", "a second arabic number to", "second arabic number to denote", "arabic number to denote the", "number to denote the isoenzyme.", "to denote the isoenzyme. an", "denote the isoenzyme. an example", "the isoenzyme. an example is", "isoenzyme. an example is cyp1a1", "an example is cyp1a1 which", "example is cyp1a1 which is", "is cyp1a1 which is the", "cyp1a1 which is the first", "which is the first enzyme", "is the first enzyme in", "the first enzyme in subfamily", "first enzyme in subfamily a", "enzyme in subfamily a of", "in subfamily a of cytochrome", "subfamily a of cytochrome p450", "a of cytochrome p450 family", "of cytochrome p450 family 1.

              the", "cytochrome p450 family 1.

              the majority", "p450 family 1.

              the majority of", "family 1.

              the majority of the", "1.

              the majority of the enzymes", "majority of the enzymes are", "of the enzymes are present", "the enzymes are present in", "enzymes are present in the", "are present in the cyp1", "present in the cyp1 4", "in the cyp1 4 families.", "the cyp1 4 families. cyp1", "cyp1 4 families. cyp1 3", "4 families. cyp1 3 are", "families. cyp1 3 are primarily", "cyp1 3 are primarily concerned", "3 are primarily concerned with", "are primarily concerned with xenobiotic", "primarily concerned with xenobiotic biotransformation", "concerned with xenobiotic biotransformation whereas", "with xenobiotic biotransformation whereas the", "xenobiotic biotransformation whereas the other", "biotransformation whereas the other cyps", "whereas the other cyps deal", "the other cyps deal primarily", "other cyps deal primarily with", "cyps deal primarily with endogenous", "deal primarily with endogenous compounds.", "primarily with endogenous compounds. the", "with endogenous compounds. the cyp", "endogenous compounds. the cyp section", "compounds. the cyp section is", "the cyp section is structured", "cyp section is structured by", "section is structured by the", "is structured by the typical", "structured by the typical substrate", "by the typical substrate they", "the typical substrate they act", "typical substrate they act upon.", "substrate they act upon. of", "they act upon. of the", "act upon. of the 57", "upon. of the 57 human", "of the 57 human cyps", "57 human cyps 7", "human cyps 7 encode", "cyps 7 encode mitochondrial", "encode mitochondrial enzymes all", "mitochondrial enzymes all involved", "enzymes all involved in", "all involved in sterol biosynthesis.", "involved in sterol biosynthesis. of", "in sterol biosynthesis. of the", "sterol biosynthesis. of the remaining", "biosynthesis. of the remaining 50", "of the remaining 50 microsomal", "the remaining 50 microsomal enzymes", "50 microsomal enzymes 20", "microsomal enzymes 20 act", "enzymes 20 act upon", "20 act upon endogenous compounds", "upon endogenous compounds 15", "endogenous compounds 15 on", "compounds 15 on xenobiotics", "15 on xenobiotics and 15", "on xenobiotics and 15 are", "xenobiotics and 15 are the", "and 15 are the so", "15 are the so called", "are the so called \\orphan", "the so called \\orphan enzymes\\", "so called \\orphan enzymes\\ with", "called \\orphan enzymes\\ with no", "\\orphan enzymes\\ with no substrate", "enzymes\\ with no substrate identified.

              the", "with no substrate identified.

              the p450", "no substrate identified.

              the p450 catalytic", "substrate identified.

              the p450 catalytic cycle", "identified.

              the p450 catalytic cycle ", "p450 catalytic cycle picture", "catalytic cycle picture ", "cycle picture shows", " picture shows the", "picture shows the steps", " shows the steps involved", "shows the steps involved when", "the steps involved when a", "steps involved when a substrate", "involved when a substrate binds", "when a substrate binds to", "a substrate binds to the", "substrate binds to the enzyme.

              ", "to the enzyme.

              1", "the enzyme.

              1 ", "enzyme.

              1 the", "color=red> 1 the normal", "1 the normal state", " the normal state of", "the normal state of a", "normal state of a p450", "state of a p450 with", "of a p450 with the", "a p450 with the iron", "p450 with the iron in", "with the iron in its", "the iron in its ferric", "in its ferric fe3+", "ferric fe3+ state.

              3+ state.

              2", "state.

              2 the", "color=red> 2 the substrate", "2 the substrate binds", " the substrate binds to", "the substrate binds to the", "to the enzyme.

              3", "the enzyme.

              3 ", "enzyme.

              3 the", "color=red> 3 the enzyme", "3 the enzyme is", " the enzyme is reduced", "the enzyme is reduced to", "enzyme is reduced to the", "is reduced to the ferrous", "to the ferrous fe2+", "ferrous fe2+ state", "fe2+ state by the", "state by the addition of", "by the addition of an", "the addition of an electron", "addition of an electron from", "of an electron from nadph", "an electron from nadph cytochrome", "electron from nadph cytochrome p450", "from nadph cytochrome p450 reductase.", "nadph cytochrome p450 reductase. the", "cytochrome p450 reductase. the bound", "p450 reductase. the bound substrate", "reductase. the bound substrate facilitates", "the bound substrate facilitates this", "bound substrate facilitates this process.

              ", "facilitates this process.

              4", "this process.

              4 5", "process.

              4 5 ", "color=red> 4 5 molecular", "4 5 molecular oxygen", "5 molecular oxygen binds", " molecular oxygen binds and", "molecular oxygen binds and forms", "oxygen binds and forms an", "binds and forms an fe2+ooh", "and forms an fe2+ooh complex", "forms an fe2+ooh complex with", "an fe2+ooh complex with the", "fe2+ooh complex with the addition", "complex with the addition of", "with the addition of a", "the addition of a proton", "addition of a proton and", "of a proton and a", "a proton and a second", "proton and a second donation", "and a second donation of", "a second donation of an", "second donation of an electron", "donation of an electron from", "of an electron from either", "an electron from either nadph", "electron from either nadph cytochrome", "from either nadph cytochrome p450", "either nadph cytochrome p450 reductase", "nadph cytochrome p450 reductase or", "cytochrome p450 reductase or cytochrome", "p450 reductase or cytochrome b5.", "reductase or cytochrome b5. a", "or cytochrome b5. a second", "cytochrome b5. a second proton", "b5. a second proton cleaves", "a second proton cleaves the", "second proton cleaves the fe2+ooh", "proton cleaves the fe2+ooh complex", "cleaves the fe2+ooh complex to", "the fe2+ooh complex to form", "fe2+ooh complex to form water.

              ", "to form water.

              6", "form water.

              6 ", "water.

              6 an", "color=red> 6 an unstable", " an unstable feo", "an unstable feo 3+", "unstable feo 3+ complex", "feo 3+ complex donates its", "3+ complex donates its oxygen", "complex donates its oxygen to", "donates its oxygen to the", "its oxygen to the substrate", "oxygen to the substrate ", "the substrate 7", "substrate 7 .", " 7 . the", "color=red> 7 . the oxidised", "7 . the oxidised substrate", ". the oxidised substrate is", "the oxidised substrate is released", "oxidised substrate is released and", "substrate is released and the", "is released and the enzyme", "released and the enzyme returns", "and the enzyme returns to", "the enzyme returns to its", "enzyme returns to its initial", "returns to its initial state", "to its initial state ", "initial state 1", "state 1 .

              " ] }, { "record_id": "GLY_000594_1_1314", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "211935", "r hsa", "hsa 211935", "r hsa 211935" ] }, { "record_id": "GLY_000594_1_1314", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fatty acids", "the cyp4", "cyp4 family", "family are", "are the", "the main", "main cyps", "cyps involved", "involved in", "in the", "the metabolism", "metabolism of", "of long", "long chain", "chain fatty", "fatty acids.", "the cyp4 family", "cyp4 family are", "family are the", "are the main", "the main cyps", "main cyps involved", "cyps involved in", "involved in the", "in the metabolism", "the metabolism of", "metabolism of long", "of long chain", "long chain fatty", "chain fatty acids.", "the cyp4 family are", "cyp4 family are the", "family are the main", "are the main cyps", "the main cyps involved", "main cyps involved in", "cyps involved in the", "involved in the metabolism", "in the metabolism of", "the metabolism of long", "metabolism of long chain", "of long chain fatty", "long chain fatty acids.", "the cyp4 family are the", "cyp4 family are the main", "family are the main cyps", "are the main cyps involved", "the main cyps involved in", "main cyps involved in the", "cyps involved in the metabolism", "involved in the metabolism of", "in the metabolism of long", "the metabolism of long chain", "metabolism of long chain fatty", "of long chain fatty acids." ] }, { "record_id": "GLY_000594_1_1315", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "211957", "r hsa", "hsa 211957", "r hsa 211957" ] }, { "record_id": "GLY_000594_1_1315", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "aromatic amines", "amines can", "can be", "be n", "n hydroxylated", "hydroxylated or", "or n", "n dealkylated", "dealkylated by", "by cyp1a2", "aromatic amines 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"buczynski et al.", "et al. 2009", "2009 vance", "vance & vance", "& vance 2008", "vance 2008 .", "5 hydroperoxy eicosatetraenoic acid", "eicosatetraenoic acid 5", "acid 5 hpete", "hpete 5", "hydroxyeicosatetraenoic acid 5s", "acid 5s hete", "5s hete and", "and 5 oxo", "5 oxo eicosatetraenoic acid", "acid 5 oxoete", "5 oxoete are", "oxoete are formed", "are formed after the", "formed after the initial", "after the initial step", "the initial step of", "initial step of arachidonate", "step of arachidonate oxidation", "of arachidonate oxidation by", "arachidonate oxidation by arachidonate", "oxidation by arachidonate 5", "by arachidonate 5 lipoxygenase", "5 lipoxygenase alox5", "alox5 buczynski", "buczynski et al. 2009", "al. 2009 vance", "2009 vance &", "vance & vance 2008", "& vance 2008 .", "hydroperoxy eicosatetraenoic acid 5", "eicosatetraenoic acid 5 hpete", "5 hpete 5", "hpete 5 hydroxyeicosatetraenoic", "5 hydroxyeicosatetraenoic acid 5s", "hydroxyeicosatetraenoic acid 5s hete", "hete and 5", "and 5 oxo eicosatetraenoic", "oxo eicosatetraenoic acid 5", "eicosatetraenoic acid 5 oxoete", "5 oxoete are formed", "oxoete are formed after", "are formed after the initial", "formed after the initial step", "after the initial step of", "the initial step of arachidonate", "initial step of arachidonate oxidation", "step of arachidonate oxidation by", "of arachidonate oxidation by arachidonate", "arachidonate oxidation by arachidonate 5", "oxidation by arachidonate 5 lipoxygenase", "arachidonate 5 lipoxygenase alox5", "alox5 buczynski et", "et al. 2009 vance", "al. 2009 vance &", "2009 vance & vance", "vance & vance 2008 ." ] }, { "record_id": "GLY_000594_1_1321", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142691", "r hsa", "hsa 2142691", "r hsa 2142691" ] }, { "record_id": "GLY_000594_1_1321", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of leukotrienes", "and eoxins", "synthesis of leukotrienes", "leukotrienes lt", "lt and", "eoxins ex", "of leukotrienes lt", "lt and eoxins", "and eoxins ex", "synthesis of leukotrienes lt", "leukotrienes lt and", "are biologically", "biologically active", "active molecules", "molecules formed", "formed in", "in response", "response to", "to inflammatory", "inflammatory stimuli.", "stimuli. they", "they cause", "cause contraction", "contraction of", "of bronchial", "bronchial smooth", "smooth muscles", "stimulation of", "of vascular", "vascular permeability", "and attraction", "attraction and", "and activation", "activation of", "of leukocytes.", "leukocytes. lts", "lts were", "were discovered", "discovered in", "in 1938", "1938 and", "and were", "were termed", "termed the", "the \\slow", "\\slow release", "release substance\\", "until their", "their structures", "structures were", "were determined", "determined in", "in 1979", "1979 and", "and they", "they were", "were then", "then renamed", "renamed to", "to leukotrienes.", "lts are", "are derived", "derived from", "from arachidonate", "arachidonate through", "through action", "action by", "by arachidonate", "arachidonate 5", "5 lipoxygenase", "alox5 .", "cysteinyl leukotrienes", "and lte4", "are generated", "generated as", "as products", "products derived", "from leukotriene", "leukotriene a4", "lta4 .", "eoxins are", "generated from", "from leukotrienes", "and resemble", "resemble cysteinyl", "leukotrienes but", "but have", "have a", "a different", "different three", "three dimensional", "dimensional structure", "murphy &", "& gijon", "gijon 2007", "hammarstrom 1983", "ma.claesson 2009", "vance &", "& vance", "vance 2008", "buczynski et", "et al.", "al. 2009", "2009 .", "leukotrienes lts", "are biologically active", "biologically active molecules", "active molecules formed", "molecules formed in", "formed in response", "in response to", "response to inflammatory", "to inflammatory stimuli.", "inflammatory stimuli. they", "stimuli. they cause", "they cause contraction", "cause contraction of", "contraction of bronchial", "of bronchial smooth", "bronchial smooth muscles", "muscles stimulation", "stimulation of vascular", "of vascular permeability", "permeability and", "and attraction and", "attraction and activation", "and activation of", "activation of leukocytes.", "of leukocytes. lts", "leukocytes. lts were", "lts were discovered", "were discovered in", "discovered in 1938", "in 1938 and", "1938 and were", "and were termed", "were termed the", "termed the \\slow", "the \\slow release", "\\slow release substance\\", "substance\\ srs", "srs until", "until their structures", "their structures were", "structures were determined", "were determined in", "determined in 1979", "in 1979 and", "1979 and they", "and they were", "they were then", "were then renamed", "then renamed to", "renamed to leukotrienes.", "leukotrienes. lts", "lts are derived", "are derived from", "derived from arachidonate", "from arachidonate through", "arachidonate through action", "through action by", "action by arachidonate", "by arachidonate 5", "arachidonate 5 lipoxygenase", "lipoxygenase alox5", ". cysteinyl", "leukotrienes ltc4", "ltc4 ltd4", "ltd4 and", "lte4 are", "are generated as", "generated as products", "as products derived", "products derived from", "derived from leukotriene", "from leukotriene a4", "a4 lta4", ". eoxins", "eoxins are generated", "are generated from", "generated from leukotrienes", "lts and", "and resemble cysteinyl", "resemble cysteinyl leukotrienes", "cysteinyl leukotrienes but", "leukotrienes but have", "but have a", "have a different", "a different three", "different three dimensional", "three dimensional structure", "structure murphy", "murphy & gijon", "& gijon 2007", "2007 hammarstrom", "1983 ma.claesson", "2009 vance", "vance & vance", "& vance 2008", "2008 buczynski", "buczynski et al.", "et al. 2009", "al. 2009 .", "lts are biologically", "are biologically active molecules", "biologically active molecules formed", "active molecules formed in", "molecules formed in response", "formed in response to", "in response to inflammatory", "response to inflammatory stimuli.", "to inflammatory stimuli. they", "inflammatory stimuli. they cause", "stimuli. they cause contraction", "they cause contraction of", "cause contraction of bronchial", "contraction of bronchial smooth", "of bronchial smooth muscles", "smooth muscles stimulation", "muscles stimulation of", "stimulation of vascular permeability", "vascular permeability and", "permeability and attraction", "and attraction and activation", "attraction and activation of", "and activation of leukocytes.", "activation of leukocytes. lts", "of leukocytes. lts were", "leukocytes. lts were discovered", "lts were discovered in", "were discovered in 1938", "discovered in 1938 and", "in 1938 and were", "1938 and were termed", "and were termed the", "were termed the \\slow", "termed the \\slow release", "the \\slow release substance\\", "release substance\\ srs", "srs until their", "until their structures were", "their structures were determined", "structures were determined in", "were determined in 1979", "determined in 1979 and", "in 1979 and they", "1979 and they were", "and they were then", "they were then renamed", "were then renamed to", "then renamed to leukotrienes.", "to leukotrienes. lts", "leukotrienes. lts are", "lts are derived from", "are derived from arachidonate", "derived from arachidonate through", "from arachidonate through action", "arachidonate through action by", "through action by arachidonate", "action by arachidonate 5", "by arachidonate 5 lipoxygenase", "5 lipoxygenase alox5", "lipoxygenase alox5 .", "alox5 . cysteinyl", ". cysteinyl leukotrienes", "cysteinyl leukotrienes ltc4", "ltd4 and lte4", "and lte4 are", "lte4 are generated", "are generated as products", "generated as products derived", "as products derived from", "products derived from leukotriene", "derived from leukotriene a4", "leukotriene a4 lta4", "a4 lta4 .", "lta4 . eoxins", ". eoxins are", "eoxins are generated from", "are generated from leukotrienes", "from leukotrienes lts", "lts and resemble", "and resemble cysteinyl leukotrienes", "resemble cysteinyl leukotrienes but", "cysteinyl leukotrienes but have", "leukotrienes but have a", "but have a different", "have a different three", "a different three dimensional", "different three dimensional structure", "dimensional structure murphy", "structure murphy &", "murphy & gijon 2007", "gijon 2007 hammarstrom", "2007 hammarstrom 1983", "hammarstrom 1983 ma.claesson", "1983 ma.claesson 2009", "ma.claesson 2009 vance", "2009 vance &", "vance & vance 2008", "vance 2008 buczynski", "2008 buczynski et", "buczynski et al. 2009", "et al. 2009 .", "leukotrienes lts are", "lts are biologically active", "are biologically active molecules formed", "biologically active molecules formed in", "active molecules formed in response", "molecules formed in response to", "formed in response to inflammatory", "in response to inflammatory stimuli.", "response to inflammatory stimuli. they", "to inflammatory stimuli. they cause", "inflammatory stimuli. they cause contraction", "stimuli. they cause contraction of", "they cause contraction of bronchial", "cause contraction of bronchial smooth", "contraction of bronchial smooth muscles", "bronchial smooth muscles stimulation", "smooth muscles stimulation of", "muscles stimulation of vascular", "of vascular permeability and", "vascular permeability and attraction", "permeability and attraction and", "and attraction and activation of", "attraction and activation of leukocytes.", "and activation of leukocytes. lts", "activation of leukocytes. lts were", "of leukocytes. lts were discovered", "leukocytes. lts were discovered in", "lts were discovered in 1938", "were discovered in 1938 and", "discovered in 1938 and were", "in 1938 and were termed", "1938 and were termed the", "and were termed the \\slow", "were termed the \\slow release", "termed the \\slow release substance\\", "\\slow release substance\\ srs", "substance\\ srs until", "srs until their structures", "until their structures were determined", "their structures were determined in", "structures were determined in 1979", "were determined in 1979 and", "determined in 1979 and they", "in 1979 and they were", "1979 and they were then", "and they were then renamed", "they were then renamed to", "were then renamed to leukotrienes.", "renamed to leukotrienes. lts", "to leukotrienes. lts are", "leukotrienes. lts are derived", "lts are derived from arachidonate", "are derived from arachidonate through", "derived from arachidonate through action", "from arachidonate through action by", "arachidonate through action by arachidonate", "through action by arachidonate 5", "action by arachidonate 5 lipoxygenase", "arachidonate 5 lipoxygenase alox5", "5 lipoxygenase alox5 .", "alox5 . cysteinyl leukotrienes", "leukotrienes ltc4 ltd4", "ltc4 ltd4 and", "and lte4 are generated", "lte4 are generated as", "are generated as products derived", "generated as products derived from", "as products derived from leukotriene", "products derived from leukotriene a4", "from leukotriene a4 lta4", "leukotriene a4 lta4 .", "lta4 . eoxins are", ". eoxins are generated", "eoxins are generated from leukotrienes", "generated from leukotrienes lts", "leukotrienes lts and", "lts and resemble cysteinyl", "and resemble cysteinyl leukotrienes but", "resemble cysteinyl leukotrienes but have", "cysteinyl leukotrienes but have a", "leukotrienes but have a different", "but have a different three", "have a different three dimensional", "a different three dimensional structure", "three dimensional structure murphy", "dimensional structure murphy &", "structure murphy & gijon", "& gijon 2007 hammarstrom", "gijon 2007 hammarstrom 1983", "hammarstrom 1983 ma.claesson 2009", "ma.claesson 2009 vance &", "2009 vance & vance", "& vance 2008 buczynski", "vance 2008 buczynski et", "2008 buczynski et al.", "buczynski et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1322", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142696", "r hsa", "hsa 2142696", "r hsa 2142696" ] }, { "record_id": "GLY_000594_1_1322", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of hepoxilins", "and trioxilins", "synthesis of hepoxilins", "hepoxilins hx", "hx and", "trioxilins trx", "of hepoxilins hx", "hx and trioxilins", "and trioxilins trx", "synthesis of hepoxilins hx", "hepoxilins hx and", "hepoxilins are", "are biologically", "biologically relevant", "relevant signalling", "signalling molecules", "molecules produced", "produced by", "by certain", "certain arachidonate", "arachidonate 12", "12 lipoxygenase", "alox12s .", ". hepoxilin", "hepoxilin a3", "and b3", "have been", "been identified", "both of", "of which", "which incorporate", "incorporate an", "an epoxide", "epoxide across", "across the", "the c", "c 11", "11 and", "and c", "c 12", "12 double", "double bond", "as well", "well as", "as an", "an additional", "additional hydroxyl", "hydroxyl moiety.", "hxa3 has", "has a", "a c", "c 8", "8 hydroxyl", "whereas the", "the hxb3", "hxb3 hydroxyl", "hydroxyl occurs", "occurs at", "at c", "c 10.", "10. the", "the epoxy", "epoxy moiety", "moiety is", "is labile", "labile and", "and can", "can be", "be hydrolyzed", "hydrolyzed either", "either by", "by a", "a hepoxilin", "hepoxilin specific", "specific epoxide", "epoxide hydrolase", "or in", "in acidic", "acidic aqueous", "aqueous solution", "solution to", "to form", "form the", "the corresponding", "corresponding diol", "diol metabolites", "metabolites trioxilin", "trioxilin a3", "buczynski et", "et al.", "al. 2009", "vance &", "& vance", "vance 2008", "2008 .", "hepoxilins are biologically", "are biologically relevant", "biologically relevant signalling", "relevant signalling molecules", "signalling molecules produced", "molecules produced by", "produced by certain", "by certain arachidonate", "certain arachidonate 12", "arachidonate 12 lipoxygenase", "lipoxygenase alox12s", "alox12s . hepoxilin", ". hepoxilin a3", "a3 hxa3", "hxa3 and", "b3 hxb3", "hxb3 have", "have been identified", "identified both", "both of which", "of which incorporate", "which incorporate an", "incorporate an epoxide", "an epoxide across", "epoxide across the", "across the c", "the c 11", "c 11 and", "11 and c", "and c 12", "c 12 double", "12 double bond", "bond as", "as well as", "well as an", "as an additional", "an additional hydroxyl", "additional hydroxyl moiety.", "moiety. hxa3", "hxa3 has a", "has a c", "a c 8", "c 8 hydroxyl", "hydroxyl whereas", "whereas the hxb3", "the hxb3 hydroxyl", "hxb3 hydroxyl occurs", "hydroxyl occurs at", "occurs at c", "at c 10.", "c 10. the", "10. the epoxy", "the epoxy moiety", "epoxy moiety is", "moiety is labile", "is labile and", "labile and can", "and can be", "can be hydrolyzed", "be hydrolyzed either", "hydrolyzed either by", "either by a", "by a hepoxilin", "a hepoxilin specific", "hepoxilin specific epoxide", "specific epoxide hydrolase", "hydrolase hxeh", "hxeh or", "or in acidic", "in acidic aqueous", "acidic aqueous solution", "aqueous solution to", "solution to form", "to form the", "form the corresponding", "the corresponding diol", "corresponding diol metabolites", "diol metabolites trioxilin", "metabolites trioxilin a3", "a3 trxa3", "trxa3 and", "b3 trxb3", "buczynski et al.", "et al. 2009", "2009 vance", "vance & vance", "& vance 2008", "vance 2008 .", "hepoxilins are biologically relevant", "are biologically relevant signalling", "biologically relevant signalling molecules", "relevant signalling molecules produced", "signalling molecules produced by", "molecules produced by certain", "produced by certain arachidonate", "by certain arachidonate 12", "certain arachidonate 12 lipoxygenase", "12 lipoxygenase alox12s", "lipoxygenase alox12s .", "alox12s . hepoxilin a3", "hepoxilin a3 hxa3", "hxa3 and b3", "and b3 hxb3", "hxb3 have been", "been identified both", "identified both of", "both of which incorporate", "of which incorporate an", "which incorporate an epoxide", "incorporate an epoxide across", "an epoxide across the", "epoxide across the c", "across the c 11", "the c 11 and", "c 11 and c", "11 and c 12", "and c 12 double", "c 12 double bond", "double bond as", "bond as well", "as well as an", "well as an additional", "as an additional hydroxyl", "an additional hydroxyl moiety.", "hydroxyl moiety. hxa3", "moiety. hxa3 has", "hxa3 has a c", "has a c 8", "a c 8 hydroxyl", "8 hydroxyl whereas", "hydroxyl whereas the", "whereas the hxb3 hydroxyl", "the hxb3 hydroxyl occurs", "hxb3 hydroxyl occurs at", "hydroxyl occurs at c", "occurs at c 10.", "at c 10. the", "c 10. the epoxy", "10. the epoxy moiety", "the epoxy moiety is", "epoxy moiety is labile", "moiety is labile and", "is labile and can", "labile and can be", "and can be hydrolyzed", "can be hydrolyzed either", "be hydrolyzed either by", "hydrolyzed either by a", "either by a hepoxilin", "by a hepoxilin specific", "a hepoxilin specific epoxide", "hepoxilin specific epoxide hydrolase", "epoxide hydrolase hxeh", "hxeh or in", "or in acidic aqueous", "in acidic aqueous solution", "acidic aqueous solution to", "aqueous solution to form", "solution to form the", "to form the corresponding", "form the corresponding diol", "the corresponding diol metabolites", "corresponding diol metabolites trioxilin", "diol metabolites trioxilin a3", "trioxilin a3 trxa3", "trxa3 and b3", "and b3 trxb3", "trxb3 buczynski", "buczynski et al. 2009", "al. 2009 vance", "2009 vance &", "vance & vance 2008", "& vance 2008 .", "hepoxilins are biologically relevant signalling", "are biologically relevant signalling molecules", "biologically relevant signalling molecules produced", "relevant signalling molecules produced by", "signalling molecules produced by certain", "molecules produced by certain arachidonate", "produced by certain arachidonate 12", "by certain arachidonate 12 lipoxygenase", "arachidonate 12 lipoxygenase alox12s", "12 lipoxygenase alox12s .", "lipoxygenase alox12s . hepoxilin", ". hepoxilin a3 hxa3", "a3 hxa3 and", "b3 hxb3 have", "hxb3 have been identified", "have been identified both", "been identified both of", "identified both of which", "both of which incorporate an", "of which incorporate an epoxide", "which incorporate an epoxide across", "incorporate an epoxide across the", "an epoxide across the c", "epoxide across the c 11", "across the c 11 and", "the c 11 and c", "c 11 and c 12", "11 and c 12 double", "and c 12 double bond", "12 double bond as", "double bond as well", "bond as well as", "as well as an additional", "well as an additional hydroxyl", "as an additional hydroxyl moiety.", "additional hydroxyl moiety. hxa3", "hydroxyl moiety. hxa3 has", "moiety. hxa3 has a", "hxa3 has a c 8", "has a c 8 hydroxyl", "c 8 hydroxyl whereas", "8 hydroxyl whereas the", "hydroxyl whereas the hxb3", "whereas the hxb3 hydroxyl occurs", "the hxb3 hydroxyl occurs at", "hxb3 hydroxyl occurs at c", "hydroxyl occurs at c 10.", "occurs at c 10. the", "at c 10. the epoxy", "c 10. the epoxy moiety", "10. the epoxy moiety is", "the epoxy moiety is labile", "epoxy moiety is labile and", "moiety is labile and can", "is labile and can be", "labile and can be hydrolyzed", "and can be hydrolyzed either", "can be hydrolyzed either by", "be hydrolyzed either by a", "hydrolyzed either by a hepoxilin", "either by a hepoxilin specific", "by a hepoxilin specific epoxide", "a hepoxilin specific epoxide hydrolase", "specific epoxide hydrolase hxeh", "hydrolase hxeh or", "hxeh or in acidic", "or in acidic aqueous solution", "in acidic aqueous solution to", "acidic aqueous solution to form", "aqueous solution to form the", "solution to form the corresponding", "to form the corresponding diol", "form the corresponding diol metabolites", "the corresponding diol metabolites trioxilin", "corresponding diol metabolites trioxilin a3", "metabolites trioxilin a3 trxa3", "a3 trxa3 and", "trxb3 buczynski et", "et al. 2009 vance", "al. 2009 vance &", "2009 vance & vance", "vance & vance 2008 ." ] }, { "record_id": "GLY_000594_1_1323", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142700", "r hsa", "hsa 2142700", "r hsa 2142700" ] }, { "record_id": "GLY_000594_1_1323", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biosynthesis of", "of lipoxins", "biosynthesis of lipoxins", "lipoxins lx", "of lipoxins lx", "biosynthesis of lipoxins lx", "lipoxins a4", "and b4", "structurally characterized", "characterized from", "from human", "human neutrophils", "neutrophils incubated", "incubated with", "with 15", "15 hydroperoxy", "hydroperoxy eicosatetraenoic", "eicosatetraenoic acid", "15 hpete", "each contain", "contain three", "three hydroxyl", "hydroxyl moieties", "moieties and", "and a", "a conjugated", "conjugated tetraene.", "tetraene. the", "the third", "third hydroxyl", "hydroxyl of", "of lxa4", "lxa4 is", "is positioned", "positioned at", "at c", "c 6", "and of", "of lxb4", "lxb4 at", "c 14.", "the action", "action of", "of arachidonate", "arachidonate 5", "5 lipoxygenase", "in concert", "concert with", "with an", "an arachidonate", "arachidonate 12", "12 lipoxygenase", "or arachidonate", "arachidonate 15", "15 lipoxygenase", "has been", "been shown", "shown to", "to produce", "produce lipoxins", "lipoxins by", "by three", "three distinct", "distinct pathways.", "neutrophil alox5", "alox5 can", "can produce", "produce and", "and secrete", "secrete leukotriene", "leukotriene a4", "that is", "is taken", "taken up", "up by", "by platelets", "where it", "it is", "is acted", "acted upon", "upon by", "by alox12", "alox12 to", "to form", "form lipoxins.", "lipoxins. likewise", "alox15s can", "can generate", "generate either", "either 15", "or 15", "15 hydro", "hydro eicosatetraenoic", "15 hete", "that can", "can be", "be taken", "by monocytes", "monocytes and", "and neutrophils", "where highly", "highly expressed", "expressed alox5", "alox5 uses", "uses it", "it to", "to generate", "generate lipoxins.", "lipoxins. finally", "aspirin acetylated", "acetylated prostaglandin", "prostaglandin g/h", "g/h synthase", "synthase 2", "rendered unable", "unable to", "to synthesize", "synthesize prostaglandins", "can act", "act as", "as a", "a 15", "15 lipoxygenase.", "lipoxygenase. this", "this leads", "leads to", "to the", "the formation", "formation of", "of 15r", "15r hete", "hete and", "and culminates", "culminates in", "in creation", "creation of", "of epi", "epi lipoxins", "which have", "have altered", "altered stereochemistry", "stereochemistry at", "at the", "the c", "c 15", "15 hydroxyl", "hydroxyl but", "but similar", "similar biological", "biological potency", "chiang et", "et al.", "al. 2006", "buczynski et", "al. 2009", "vance &", "& vance", "vance 2008", "stsiapanava et", "al. 2017", "2017 .", "a4 lxa4", "lxa4 and", "b4 lxb4", "structurally characterized from", "characterized from human", "from human neutrophils", "human neutrophils incubated", "neutrophils incubated with", "incubated with 15", "with 15 hydroperoxy", "15 hydroperoxy eicosatetraenoic", "hydroperoxy eicosatetraenoic acid", "acid 15", "each contain three", "contain three hydroxyl", "three hydroxyl moieties", "hydroxyl moieties and", "moieties and a", "and a conjugated", "a conjugated tetraene.", "conjugated tetraene. the", "tetraene. the third", "the third hydroxyl", "third hydroxyl of", "hydroxyl of lxa4", "of lxa4 is", "lxa4 is positioned", "is positioned at", "positioned at c", "at c 6", "6 and", "and of lxb4", "of lxb4 at", "lxb4 at c", "at c 14.", "14. the", "the action of", "action of arachidonate", "of arachidonate 5", "arachidonate 5 lipoxygenase", "lipoxygenase alox5", "in concert with", "concert with an", "with an arachidonate", "an arachidonate 12", "arachidonate 12 lipoxygenase", "lipoxygenase alox12", "alox12 or", "or arachidonate 15", "arachidonate 15 lipoxygenase", "lipoxygenase alox15", "alox15 activity", "activity has", "has been shown", "been shown to", "shown to produce", "to produce lipoxins", "produce lipoxins by", "lipoxins by three", "by three distinct", "three distinct pathways.", "pathways. neutrophil", "neutrophil alox5 can", "alox5 can produce", "can produce and", "produce and secrete", "and secrete leukotriene", "secrete leukotriene a4", "a4 lta4", "lta4 that", "that is taken", "is taken up", "taken up by", "up by platelets", "platelets where", "where it is", "it is acted", "is acted upon", "acted upon by", "upon by alox12", "by alox12 to", "alox12 to form", "to form lipoxins.", "form lipoxins. likewise", "likewise alox15s", "alox15s can generate", "can generate either", "generate either 15", "either 15 hydroperoxy", "hpete or", "or 15 hydro", "15 hydro eicosatetraenoic", "hydro eicosatetraenoic acid", "hete that", "that can be", "can be taken", "be taken up", "up by monocytes", "by monocytes and", "monocytes and neutrophils", "neutrophils where", "where highly expressed", "highly expressed alox5", "expressed alox5 uses", "alox5 uses it", "uses it to", "it to generate", "to generate lipoxins.", "generate lipoxins. finally", "finally aspirin", "aspirin acetylated prostaglandin", "acetylated prostaglandin g/h", "prostaglandin g/h synthase", "g/h synthase 2", "2 ptgs2", "rendered unable to", "unable to synthesize", "to synthesize prostaglandins", "prostaglandins can", "can act as", "act as a", "as a 15", "a 15 lipoxygenase.", "15 lipoxygenase. this", "lipoxygenase. this leads", "this leads to", "leads to the", "to the formation", "the formation of", "formation of 15r", "of 15r hete", "15r hete and", "hete and culminates", "and culminates in", "culminates in creation", "in creation of", "creation of epi", "of epi lipoxins", "lipoxins which", "which have altered", "have altered stereochemistry", "altered stereochemistry at", "stereochemistry at the", "at the c", "the c 15", "c 15 hydroxyl", "15 hydroxyl but", "hydroxyl but similar", "but similar biological", "similar biological potency", "potency chiang", "chiang et al.", "et al. 2006", "2006 buczynski", "buczynski et al.", "et al. 2009", "2009 vance", "vance & vance", "& vance 2008", "2008 stsiapanava", "stsiapanava et al.", "et al. 2017", "al. 2017 .", "lipoxins a4 lxa4", "lxa4 and b4", "and b4 lxb4", "lxb4 structurally", "structurally characterized from human", "characterized from human neutrophils", "from human neutrophils incubated", "human neutrophils incubated with", "neutrophils incubated with 15", "incubated with 15 hydroperoxy", "with 15 hydroperoxy eicosatetraenoic", "15 hydroperoxy eicosatetraenoic acid", "eicosatetraenoic acid 15", "acid 15 hpete", "hpete each", "each contain three hydroxyl", "contain three hydroxyl moieties", "three hydroxyl moieties and", "hydroxyl moieties and a", "moieties and a conjugated", "and a conjugated tetraene.", "a conjugated tetraene. the", "conjugated tetraene. the third", "tetraene. the third hydroxyl", "the third hydroxyl of", "third hydroxyl of lxa4", "hydroxyl of lxa4 is", "of lxa4 is positioned", "lxa4 is positioned at", "is positioned at c", "positioned at c 6", "c 6 and", "6 and of", "and of lxb4 at", "of lxb4 at c", "lxb4 at c 14.", "c 14. the", "14. the action", "the action of arachidonate", "action of arachidonate 5", "of arachidonate 5 lipoxygenase", "5 lipoxygenase alox5", "alox5 in", "in concert with an", "concert with an arachidonate", "with an arachidonate 12", "an arachidonate 12 lipoxygenase", "12 lipoxygenase alox12", "alox12 or arachidonate", "or arachidonate 15 lipoxygenase", "15 lipoxygenase alox15", "activity has been", "has been shown to", "been shown to produce", "shown to produce lipoxins", "to produce lipoxins by", "produce lipoxins by three", "lipoxins by three distinct", "by three distinct pathways.", "distinct pathways. neutrophil", "pathways. neutrophil alox5", "neutrophil alox5 can produce", "alox5 can produce and", "can produce and secrete", "produce and secrete leukotriene", "and secrete leukotriene a4", "leukotriene a4 lta4", "lta4 that is", "that is taken up", "is taken up by", "taken up by platelets", "by platelets where", "platelets where it", "where it is acted", "it is acted upon", "is acted upon by", "acted upon by alox12", "upon by alox12 to", "by alox12 to form", "alox12 to form lipoxins.", "to form lipoxins. likewise", "lipoxins. likewise alox15s", "likewise alox15s can", "alox15s can generate either", "can generate either 15", "generate either 15 hydroperoxy", "either 15 hydroperoxy eicosatetraenoic", "15 hpete or", "hpete or 15", "or 15 hydro eicosatetraenoic", "15 hydro eicosatetraenoic acid", "acid 15 hete", "15 hete that", "hete that can", "that can be taken", "can be taken up", "be taken up by", "taken up by monocytes", "up by monocytes and", "by monocytes and neutrophils", "and neutrophils where", "neutrophils where highly", "where highly expressed alox5", "highly expressed alox5 uses", "expressed alox5 uses it", "alox5 uses it to", "uses it to generate", "it to generate lipoxins.", "to generate lipoxins. finally", "lipoxins. finally aspirin", "finally aspirin acetylated", "aspirin acetylated prostaglandin g/h", "acetylated prostaglandin g/h synthase", "prostaglandin g/h synthase 2", "synthase 2 ptgs2", "ptgs2 rendered", "rendered unable to synthesize", "unable to synthesize prostaglandins", "synthesize prostaglandins can", "prostaglandins can act", "can act as a", "act as a 15", "as a 15 lipoxygenase.", "a 15 lipoxygenase. this", "15 lipoxygenase. this leads", "lipoxygenase. this leads to", "this leads to the", "leads to the formation", "to the formation of", "the formation of 15r", "formation of 15r hete", "of 15r hete and", "15r hete and culminates", "hete and culminates in", "and culminates in creation", "culminates in creation of", "in creation of epi", "creation of epi lipoxins", "epi lipoxins which", "lipoxins which have", "which have altered stereochemistry", "have altered stereochemistry at", "altered stereochemistry at the", "stereochemistry at the c", "at the c 15", "the c 15 hydroxyl", "c 15 hydroxyl but", "15 hydroxyl but similar", "hydroxyl but similar biological", "but similar biological potency", "biological potency chiang", "potency chiang et", "chiang et al. 2006", "al. 2006 buczynski", "2006 buczynski et", "buczynski et al. 2009", "al. 2009 vance", "2009 vance &", "vance & vance 2008", "vance 2008 stsiapanava", "2008 stsiapanava et", "stsiapanava et al. 2017", "et al. 2017 .", "a4 lxa4 and", "lxb4 structurally characterized", "structurally characterized from human neutrophils", "characterized from human neutrophils incubated", "from human neutrophils incubated with", "human neutrophils incubated with 15", "neutrophils incubated with 15 hydroperoxy", "incubated with 15 hydroperoxy eicosatetraenoic", "with 15 hydroperoxy eicosatetraenoic acid", "hydroperoxy eicosatetraenoic acid 15", "eicosatetraenoic acid 15 hpete", "15 hpete each", "hpete each contain", "each contain three hydroxyl moieties", "contain three hydroxyl moieties and", "three hydroxyl moieties and a", "hydroxyl moieties and a conjugated", "moieties and a conjugated tetraene.", "and a conjugated tetraene. the", "a conjugated tetraene. the third", "conjugated tetraene. the third hydroxyl", "tetraene. the third hydroxyl of", "the third hydroxyl of lxa4", "third hydroxyl of lxa4 is", "hydroxyl of lxa4 is positioned", "of lxa4 is positioned at", "lxa4 is positioned at c", "is positioned at c 6", "at c 6 and", "c 6 and of", "6 and of lxb4", "and of lxb4 at c", "of lxb4 at c 14.", "at c 14. the", "c 14. the action", "14. the action of", "the action of arachidonate 5", "action of arachidonate 5 lipoxygenase", "arachidonate 5 lipoxygenase alox5", "alox5 in concert", "in concert with an arachidonate", "concert with an arachidonate 12", "with an arachidonate 12 lipoxygenase", "arachidonate 12 lipoxygenase alox12", "lipoxygenase alox12 or", "alox12 or arachidonate 15", "arachidonate 15 lipoxygenase alox15", "lipoxygenase alox15 activity", "alox15 activity has", "activity has been shown", "has been shown to produce", "been shown to produce lipoxins", "shown to produce lipoxins by", "to produce lipoxins by three", "produce lipoxins by three distinct", "lipoxins by three distinct pathways.", "three distinct pathways. neutrophil", "distinct pathways. neutrophil alox5", "pathways. neutrophil alox5 can", "neutrophil alox5 can produce and", "alox5 can produce and secrete", "can produce and secrete leukotriene", "produce and secrete leukotriene a4", "secrete leukotriene a4 lta4", "a4 lta4 that", "lta4 that is taken", "that is taken up by", "is taken up by platelets", "up by platelets where", "by platelets where it", "platelets where it is", "where it is acted upon", "it is acted upon by", "is acted upon by alox12", "acted upon by alox12 to", "upon by alox12 to form", "by alox12 to form lipoxins.", "alox12 to form lipoxins. likewise", "form lipoxins. likewise alox15s", "lipoxins. likewise alox15s can", "likewise alox15s can generate", "alox15s can generate either 15", "can generate either 15 hydroperoxy", "generate either 15 hydroperoxy eicosatetraenoic", "either 15 hydroperoxy eicosatetraenoic acid", "15 hpete or 15", "hpete or 15 hydro", "or 15 hydro eicosatetraenoic acid", "hydro eicosatetraenoic acid 15", "eicosatetraenoic acid 15 hete", "15 hete that can", "hete that can be", "that can be taken up", "can be taken up by", "be taken up by monocytes", "taken up by monocytes and", "up by monocytes and neutrophils", "monocytes and neutrophils where", "and neutrophils where highly", "neutrophils where highly expressed", "where highly expressed alox5 uses", "highly expressed alox5 uses it", "expressed alox5 uses it to", "alox5 uses it to generate", "uses it to generate lipoxins.", "it to generate lipoxins. finally", "generate lipoxins. finally aspirin", "lipoxins. finally aspirin acetylated", "finally aspirin acetylated prostaglandin", "aspirin acetylated prostaglandin g/h synthase", "acetylated prostaglandin g/h synthase 2", "g/h synthase 2 ptgs2", "ptgs2 rendered unable", "rendered unable to synthesize prostaglandins", "to synthesize prostaglandins can", "synthesize prostaglandins can act", "prostaglandins can act as", "can act as a 15", "act as a 15 lipoxygenase.", "as a 15 lipoxygenase. this", "a 15 lipoxygenase. this leads", "15 lipoxygenase. this leads to", "lipoxygenase. this leads to the", "this leads to the formation", "leads to the formation of", "to the formation of 15r", "the formation of 15r hete", "formation of 15r hete and", "of 15r hete and culminates", "15r hete and culminates in", "hete and culminates in creation", "and culminates in creation of", "culminates in creation of epi", "in creation of epi lipoxins", "of epi lipoxins which", "epi lipoxins which have", "lipoxins which have altered", "which have altered stereochemistry at", "have altered stereochemistry at the", "altered stereochemistry at the c", "stereochemistry at the c 15", "at the c 15 hydroxyl", "the c 15 hydroxyl but", "c 15 hydroxyl but similar", "15 hydroxyl but similar biological", "hydroxyl but similar biological potency", "similar biological potency chiang", "biological potency chiang et", "potency chiang et al.", "et al. 2006 buczynski", "al. 2006 buczynski et", "2006 buczynski et al.", "et al. 2009 vance", "al. 2009 vance &", "2009 vance & vance", "& vance 2008 stsiapanava", "vance 2008 stsiapanava et", "2008 stsiapanava et al.", "stsiapanava et al. 2017 ." ] }, { "record_id": "GLY_000594_1_1324", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2142816", "r hsa", "hsa 2142816", "r hsa 2142816" ] }, { "record_id": "GLY_000594_1_1324", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "16 20", "hydroxyeicosatetraenoic acids", "of 16", "20 hydroxyeicosatetraenoic", "acids hete", "synthesis of 16", "of 16 20", "16 20 hydroxyeicosatetraenoic", "20 hydroxyeicosatetraenoic acids", "hydroxyeicosatetraenoic acids hete", "synthesis of 16 20", "16 20 hydroxyeicosatetraenoic acids", "similar to", "to the", "the lipoxygenases", "cytochrome p450", "enzymes catalyse", "catalyse the", "the hydroxylation", "hydroxylation and", "and epoxygenation", "epoxygenation of", "of arachidonate.", "whereas lipoxygenases", "lipoxygenases use", "use an", "an active", "active non", "non heme", "heme iron", "iron to", "to abstract", "abstract hydrogen", "hydrogen directly", "directly from", "from arachidonate", "cyps contain", "contain a", "a heme", "iron active", "active site", "site that", "that oxidizes", "oxidizes its", "its substrate", "substrate by", "by a", "a different", "different mechanism.", "they hydroxylate", "hydroxylate arachidonate", "arachidonate between", "between c", "c 5", "5 and", "and c", "c 15", "15 to", "to produce", "produce lipoxygenase", "lipoxygenase like", "like hydroxyeicosatetraenoates", "and add", "add a", "a hydroxyl", "hydroxyl moiety", "moiety to", "the sp3", "sp3 hybridized", "hybridized omega", "omega carbons", "carbons to", "to form", "form a", "a unique", "unique class", "class of", "of hetes.", "the transfer", "transfer of", "of oxygen", "oxygen to", "the unstable", "unstable arachidonate", "arachidonate intermediate", "intermediate terminates", "terminates the", "the reaction", "reaction by", "by forming", "forming hete", "hete or", "or epoxy", "epoxy eicosatrienoate", "capdevila et", "et al.", "al. 2000", "buczynski et", "al. 2009", "vance &", "& vance", "vance 2008", "2008 .", "similar to the", "to the lipoxygenases", "lipoxygenases cytochrome", "p450 cyp", "cyp enzymes", "enzymes catalyse the", "catalyse the hydroxylation", "the hydroxylation and", "hydroxylation and epoxygenation", "and epoxygenation of", "epoxygenation of arachidonate.", "arachidonate. however", "however whereas", "whereas lipoxygenases use", "lipoxygenases use an", "use an active", "an active non", "active non heme", "non heme iron", "heme iron to", "iron to abstract", "to abstract hydrogen", "abstract hydrogen directly", "hydrogen directly from", "directly from arachidonate", "arachidonate cyps", "cyps contain a", "contain a heme", "a heme iron", "heme iron active", "iron active site", "active site that", "site that oxidizes", "that oxidizes its", "oxidizes its substrate", "its substrate by", "substrate by a", "by a different", "a different mechanism.", "mechanism. they", "they hydroxylate arachidonate", "hydroxylate arachidonate between", "arachidonate between c", "between c 5", "c 5 and", "5 and c", "and c 15", "c 15 to", "15 to produce", "to produce lipoxygenase", "produce 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"vance 2008 .", "similar to the lipoxygenases", "the lipoxygenases cytochrome", "lipoxygenases cytochrome p450", "cytochrome p450 cyp", "cyp enzymes catalyse", "enzymes catalyse the hydroxylation", "catalyse the hydroxylation and", "the hydroxylation and epoxygenation", "hydroxylation and epoxygenation of", "and epoxygenation of arachidonate.", "of arachidonate. however", "however whereas lipoxygenases", "whereas lipoxygenases use an", "lipoxygenases use an active", "use an active non", "an active non heme", "active non heme iron", "non heme iron to", "heme iron to abstract", "iron to abstract hydrogen", "to abstract hydrogen directly", "abstract hydrogen directly from", "hydrogen directly from arachidonate", "from arachidonate cyps", "arachidonate cyps contain", "cyps contain a heme", "contain a heme iron", "a heme iron active", "heme iron active site", "iron active site that", "active site that oxidizes", "site that oxidizes its", "that oxidizes its substrate", "oxidizes its 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"oxygen to the unstable", "to the unstable arachidonate", "the unstable arachidonate intermediate", "unstable arachidonate intermediate terminates", "arachidonate intermediate terminates the", "intermediate terminates the reaction", "terminates the reaction by", "the reaction by forming", "reaction by forming hete", "by forming hete or", "forming hete or epoxy", "hete or epoxy eicosatrienoate", "epoxy eicosatrienoate eets", "eets respectively", "respectively capdevila et", "capdevila et al. 2000", "al. 2000 buczynski", "2000 buczynski et", "buczynski et al. 2009", "al. 2009 vance", "2009 vance &", "vance & vance 2008", "& vance 2008 .", "to the lipoxygenases cytochrome", "the lipoxygenases cytochrome p450", "p450 cyp enzymes", "cyp enzymes catalyse the", "enzymes catalyse the hydroxylation and", "catalyse the hydroxylation and epoxygenation", "the hydroxylation and epoxygenation of", "hydroxylation and epoxygenation of arachidonate.", "epoxygenation of arachidonate. however", "arachidonate. however whereas", "however whereas lipoxygenases use", "whereas lipoxygenases use an active", "lipoxygenases use an active non", "use an active non heme", "an active non heme iron", "active non heme iron to", "non heme iron to abstract", "heme iron to abstract hydrogen", "iron to abstract hydrogen directly", "to abstract hydrogen directly from", "abstract hydrogen directly from arachidonate", "directly from arachidonate cyps", "from arachidonate cyps contain", "arachidonate cyps contain a", "cyps contain a heme iron", "contain a heme iron active", "a heme iron active site", "heme iron active site that", "iron active site that oxidizes", "active site that oxidizes its", "site that oxidizes its substrate", "that oxidizes its substrate by", "oxidizes its substrate by a", "its substrate by a different", "substrate by a different mechanism.", "a different mechanism. they", "different mechanism. they hydroxylate", "mechanism. they hydroxylate arachidonate", "they hydroxylate 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              ", "complex.

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              notch2", ".

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              there", ".

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              ", "coactivator complex.

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              the", "notch1 targets.

              the promoter", "targets.

              the promoter of", "promoter of fcer2", "fcer2 cd23a", "cd23a contains", "contains several rbes", "several rbes that", "rbes that are", "that are occupied", "are occupied by", "occupied by notch2", "by notch2 but", "notch2 but not", "but not notch1", "not notch1 coactivator", "notch1 coactivator complexes", "complexes and", "and notch2 activation", "notch2 activation stimulates", "activation stimulates fcer2", "stimulates fcer2 transcription.", "fcer2 transcription. overexpression", "transcription. overexpression of", "overexpression of fcer2", "cd23a is", "is a hallmark", "a hallmark of", "hallmark of b", "of b cell", "b cell chronic", "cell chronic lymphocytic", "chronic lymphocytic leukemia", "leukemia b", "cll and", "and correlates with", "correlates with the", "with the malfunction", "the malfunction of", "malfunction of apoptosis", "apoptosis which", "which is thought", "is thought be", "thought be an", "be an underlying", "an underlying mechanism", "underlying mechanism of", "mechanism of b", "of b cll", "b cll development.", "cll development. the", "development. the epstein", "the epstein barr", "epstein barr virus", "barr virus protein", "virus protein ebna2", "protein ebna2 can", "ebna2 can also", "can also activate", "also activate fcer2", "activate fcer2 transcription", "fcer2 transcription through", "transcription through rbes", "rbes possibly", "possibly by mimicking", "by mimicking notch2", "mimicking notch2 signaling", "signaling hubmann", "hubmann et al.", "al. 2002 .

              notch2", "2002 .

              notch2 coactivator", ".

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              there", "2008 .

              there are", ".

              there are indications", "are indications that", "indications that notch2", "that notch2 genetically", "notch2 genetically interacts", "genetically interacts with", "interacts with hepatocyte", "with hepatocyte nuclear", "hepatocyte nuclear factor", "nuclear factor 1", "factor 1 beta", "beta hnf1b", "hnf1b in", "in kidney development", "development massa", "massa et al.", "et al. 2013", "2013 heliot", "heliot et al.", "2013 and", "and with hepatocyte", "nuclear factor 6", "6 hnf6", "hnf6 in", "in bile duct", "bile duct formation", "formation vanderpool", "vanderpool et al.", "et al. 2012", "but the exact", "the exact nature", "exact nature of", "nature of these", "of these genetic", "these genetic interactions", "genetic interactions has", "interactions has not", "has not been", "not been defined.

              ", "the nucleus nicd2", "nucleus nicd2 forms", "nicd2 forms a complex", "forms a complex with", "a complex with rbpj", "with rbpj cbf1", "csl and maml", "and maml mastermind", "maml mastermind .", "mastermind . nicd2:rbpj:maml complex", ". nicd2:rbpj:maml complex activates", "nicd2:rbpj:maml complex activates transcription", "complex activates transcription from", "activates transcription from rbpj", "transcription from rbpj binding", "from rbpj binding promoter", "rbpj binding promoter elements", "promoter elements rbes", "rbes wu", "wu et al. 2000", "et al. 2000 .", "al. 2000 . besides", "2000 . besides nicd2", "besides nicd2 rbpj", "nicd2 rbpj and", "and maml notch2", "maml notch2 coactivator", "notch2 coactivator complex likely", "coactivator complex likely includes", "complex likely includes other", "likely includes other proteins", "other proteins shown", "proteins shown as", "shown as components of", "as components of the", "components of the notch1", "of the notch1 coactivator", "the notch1 coactivator complex.

              ", "notch1 coactivator complex.

              notch2", "coactivator complex.

              notch2 coactivator", "complex.

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              the", "known notch1 targets.

              the promoter", "notch1 targets.

              the promoter of", "targets.

              the promoter of fcer2", "of fcer2 cd23a", "cd23a contains several", "contains several rbes that", "several rbes that are", "rbes that are occupied", "that are occupied by", "are occupied by notch2", "occupied by notch2 but", "by notch2 but not", "notch2 but not notch1", "but not notch1 coactivator", "not notch1 coactivator complexes", "coactivator complexes and", "complexes and notch2", "and notch2 activation stimulates", "notch2 activation stimulates fcer2", "activation stimulates fcer2 transcription.", "stimulates fcer2 transcription. overexpression", "fcer2 transcription. overexpression of", "transcription. overexpression of fcer2", "cd23a is a", "is a hallmark of", "a hallmark of b", "hallmark of b cell", "of b cell chronic", "b cell chronic lymphocytic", "cell chronic lymphocytic leukemia", "lymphocytic leukemia b", "leukemia b cll", "b cll and", "cll and correlates", "and correlates with the", "correlates with the malfunction", "with the malfunction of", "the malfunction of apoptosis", "of apoptosis which", "apoptosis which is", "which is thought be", "is thought be an", "thought be an underlying", "be an underlying mechanism", "an underlying mechanism of", "underlying mechanism of b", "mechanism of b cll", "of b cll development.", "b cll development. the", "cll development. the epstein", "development. the epstein barr", "the epstein barr virus", "epstein barr virus protein", "barr virus protein ebna2", "virus protein ebna2 can", "protein ebna2 can also", "ebna2 can also activate", "can also activate fcer2", "also activate fcer2 transcription", "activate fcer2 transcription through", "fcer2 transcription through rbes", "through rbes possibly", "rbes possibly by", "possibly by mimicking notch2", "by mimicking notch2 signaling", "notch2 signaling hubmann", "signaling hubmann et", "hubmann et al. 2002", "et al. 2002 .

              notch2", "al. 2002 .

              notch2 coactivator", "2002 .

              notch2 coactivator complex", ".

              notch2 coactivator complex occupies", "coactivator complex occupies the", "complex occupies the proximal", "occupies the proximal rbe", "the proximal rbe of", "proximal rbe of the", "rbe of the gzmb", "the gzmb granzyme", "gzmb granzyme b", "granzyme b promoter", "b promoter and", "promoter and at the", "and at the same", "at the same time", "the same time interacts", "same time interacts with", "time interacts with phosphorylated", "interacts with phosphorylated creb1", "phosphorylated creb1 bound", "creb1 bound to", "bound to an adjacent", "to an adjacent cre", "an adjacent cre site.", "adjacent cre site. ep300", "cre site. ep300 transcriptional", "site. ep300 transcriptional coactivator", "ep300 transcriptional coactivator is", "transcriptional coactivator is also", "coactivator is also recruited", "is also recruited to", "also recruited to this", "recruited to this complex", "to this complex through", "this complex through association", "complex through association with", "through association with creb1", "with creb1 maekawa", "creb1 maekawa et", "maekawa et al. 2008", "et al. 2008 .", "al. 2008 . notch2", "2008 . notch2 coactivator", ". notch2 coactivator complex", "notch2 coactivator complex together", "coactivator complex together with", "complex together with crebp1", "together with crebp1 and", "with crebp1 and ep300", "crebp1 and ep300 stimulates", "and ep300 stimulates transcription", "ep300 stimulates transcription of", "stimulates transcription of gzmb", "of gzmb granzyme", "b which", "which is important for", "is important for the", "important for the cytotoxic", "for the cytotoxic function", "the cytotoxic function of", "cytotoxic function of cd8+", "function of cd8+ t", "of cd8+ t cells", "t cells maekawa", "cells maekawa et", "et al. 2008 .

              there", "al. 2008 .

              there are", "2008 .

              there are indications", ".

              there are indications that", "are indications that notch2", "indications that notch2 genetically", "that notch2 genetically interacts", "notch2 genetically interacts with", "genetically interacts with hepatocyte", "interacts with hepatocyte nuclear", "with hepatocyte nuclear factor", "hepatocyte nuclear factor 1", "nuclear factor 1 beta", "1 beta hnf1b", "hnf1b in kidney", "kidney development massa", "development massa et", "massa et al. 2013", "al. 2013 heliot", "2013 heliot et", "heliot et al. 2013", "al. 2013 and", "2013 and with", "and with hepatocyte nuclear", "hepatocyte nuclear factor 6", "factor 6 hnf6", "hnf6 in bile", "in bile duct formation", "duct formation vanderpool", "formation vanderpool et", "vanderpool et al. 2012", "2012 but", "but the exact nature", "the exact nature of", "exact nature of these", "nature of these genetic", "of these genetic interactions", "these genetic interactions has", "genetic interactions has not", "interactions has not been", "has not been defined.

              ", "in the nucleus nicd2", "the nucleus nicd2 forms", "nucleus nicd2 forms a", "nicd2 forms a complex with", "forms a complex with rbpj", "complex with rbpj cbf1", "rbpj cbf1 csl", "cbf1 csl and", "and maml mastermind .", "maml mastermind . nicd2:rbpj:maml", "mastermind . nicd2:rbpj:maml complex activates", ". nicd2:rbpj:maml complex activates transcription", "nicd2:rbpj:maml complex activates transcription from", "complex activates transcription from rbpj", "activates transcription from rbpj binding", "transcription from rbpj binding promoter", "from rbpj binding promoter elements", "binding promoter elements rbes", "rbes wu et", "wu et al. 2000 .", "et al. 2000 . besides", "al. 2000 . besides nicd2", ". besides nicd2 rbpj", "besides nicd2 rbpj and", "nicd2 rbpj and maml", "rbpj and maml notch2", "and maml notch2 coactivator", "maml notch2 coactivator complex", "notch2 coactivator complex likely includes", "coactivator complex likely includes other", "complex likely includes other proteins", "includes other proteins shown", "other proteins shown as", "proteins shown as components", "shown as components of the", "as components of the notch1", "components of the notch1 coactivator", "of the notch1 coactivator complex.

              ", "the notch1 coactivator complex.

              notch2", "notch1 coactivator complex.

              notch2 coactivator", "coactivator complex.

              notch2 coactivator complex", "complex.

              notch2 coactivator complex directly", "notch2 coactivator complex directly stimulates", "coactivator complex directly stimulates transcription", "complex directly stimulates transcription of", "directly stimulates transcription of hes1", "stimulates transcription of hes1 and", "transcription of hes1 and hes5", "of hes1 and hes5 genes", "and hes5 genes shimizu", "hes5 genes shimizu et", "genes shimizu et al.", "al. 2002 both", "2002 both of", "both of which are known", "of which are known notch1", "which are known notch1 targets.

              the", "are known notch1 targets.

              the promoter", "known notch1 targets.

              the promoter of", "notch1 targets.

              the promoter of fcer2", "promoter of fcer2 cd23a", "fcer2 cd23a contains", "cd23a contains several rbes", "contains several rbes that are", "several rbes that are occupied", "rbes that are occupied by", "that are occupied by notch2", "are occupied by notch2 but", "occupied by notch2 but not", "by notch2 but not notch1", "notch2 but not notch1 coactivator", "but not notch1 coactivator complexes", "notch1 coactivator complexes and", "coactivator complexes and notch2", "complexes and notch2 activation", "and notch2 activation stimulates fcer2", "notch2 activation stimulates fcer2 transcription.", "activation stimulates fcer2 transcription. overexpression", "stimulates fcer2 transcription. overexpression of", "fcer2 transcription. overexpression of fcer2", "overexpression of fcer2 cd23a", "fcer2 cd23a is", "cd23a is a hallmark", "is a hallmark of b", "a hallmark of b cell", "hallmark of b cell chronic", "of b cell chronic lymphocytic", "b cell chronic lymphocytic leukemia", "chronic lymphocytic leukemia b", "lymphocytic leukemia b cll", "b cll and correlates", "cll and correlates with", "and correlates with the malfunction", "correlates with the malfunction of", "with the malfunction of apoptosis", "malfunction of apoptosis which", "of apoptosis which is", "apoptosis which is thought", "which is thought be an", "is thought be an underlying", "thought be an underlying mechanism", "be an underlying mechanism of", "an underlying mechanism of b", "underlying mechanism of b cll", "mechanism of b cll development.", "of b cll development. the", "b cll development. the epstein", "cll development. the epstein barr", "development. the epstein barr virus", "the epstein barr virus protein", "epstein barr virus protein ebna2", "barr virus protein ebna2 can", "virus protein ebna2 can also", "protein ebna2 can also activate", "ebna2 can also activate fcer2", "can also activate fcer2 transcription", "also activate fcer2 transcription through", "activate fcer2 transcription through rbes", "transcription through rbes possibly", "through rbes possibly by", "rbes possibly by mimicking", "possibly by mimicking notch2 signaling", "mimicking notch2 signaling hubmann", "notch2 signaling hubmann et", "signaling hubmann et al.", "hubmann et al. 2002 .

              notch2", "et al. 2002 .

              notch2 coactivator", "al. 2002 .

              notch2 coactivator complex", "2002 .

              notch2 coactivator complex occupies", ".

              notch2 coactivator complex occupies the", "coactivator complex occupies the proximal", "complex occupies the proximal rbe", "occupies the proximal rbe of", "the proximal rbe of the", "proximal rbe of the gzmb", "of the gzmb granzyme", "the gzmb granzyme b", "granzyme b promoter and", "b promoter and at", "promoter and at the same", "and at the same time", "at the same time interacts", "the same time interacts with", "same time interacts with phosphorylated", "time interacts with phosphorylated creb1", "with phosphorylated creb1 bound", "phosphorylated creb1 bound to", "creb1 bound to an", "bound to an adjacent cre", "to an adjacent cre site.", "an adjacent cre site. ep300", "adjacent cre site. ep300 transcriptional", "cre site. ep300 transcriptional coactivator", "site. ep300 transcriptional coactivator is", "ep300 transcriptional coactivator is also", "transcriptional coactivator is also recruited", "coactivator is also recruited to", "is also recruited to this", "also recruited to this complex", "recruited to this complex through", "to this complex through association", "this complex through association with", "complex through association with creb1", "association with creb1 maekawa", "with creb1 maekawa et", "creb1 maekawa et al.", "maekawa et al. 2008 .", "et al. 2008 . notch2", "al. 2008 . notch2 coactivator", "2008 . notch2 coactivator complex", ". notch2 coactivator complex together", "notch2 coactivator complex together with", "coactivator complex together with crebp1", "complex together with crebp1 and", "together with crebp1 and ep300", "with crebp1 and ep300 stimulates", "crebp1 and ep300 stimulates transcription", "and ep300 stimulates transcription of", "ep300 stimulates transcription of gzmb", "transcription of gzmb granzyme", "of gzmb granzyme b", "granzyme b which", "b which is", "which is important for the", "is important for the cytotoxic", "important for the cytotoxic function", "for the cytotoxic function of", "the cytotoxic function of cd8+", "cytotoxic function of cd8+ t", "function of cd8+ t cells", "cd8+ t cells maekawa", "t cells maekawa et", "cells maekawa et al.", "maekawa et al. 2008 .

              there", "et al. 2008 .

              there are", "al. 2008 .

              there are indications", "2008 .

              there are indications that", ".

              there are indications that notch2", "are indications that notch2 genetically", "indications that notch2 genetically interacts", "that notch2 genetically interacts with", "notch2 genetically interacts with hepatocyte", "genetically interacts with hepatocyte nuclear", "interacts with hepatocyte nuclear factor", "with hepatocyte nuclear factor 1", "hepatocyte nuclear factor 1 beta", "factor 1 beta hnf1b", "beta hnf1b in", "hnf1b in kidney development", "in kidney development massa", "kidney development massa et", "development massa et al.", "et al. 2013 heliot", "al. 2013 heliot et", "2013 heliot et al.", "et al. 2013 and", "al. 2013 and with", "2013 and with hepatocyte", "and with hepatocyte nuclear factor", "with hepatocyte nuclear factor 6", "nuclear factor 6 hnf6", "6 hnf6 in", "hnf6 in bile duct", "bile duct formation vanderpool", "duct formation vanderpool et", "formation vanderpool et al.", "al. 2012 but", "2012 but the", "but the exact nature of", "the exact nature of these", "exact nature of these genetic", "nature of these genetic interactions", "of these genetic interactions has", "these genetic interactions has not", "genetic interactions has not been", "interactions has not been defined.

              " ] }, { "record_id": "GLY_000594_1_1327", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206285", "r hsa", "hsa 2206285", "r hsa 2206285" ] }, { "record_id": "GLY_000594_1_1327", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps vi", "maroteaux lamy", "lamy syndrome", "maroteaux lamy syndrome", "vi maroteaux", "mps vi maroteaux", "vi maroteaux lamy", "mucopolysaccharidosis type", "type vi", "polydystrophic dwarfism", "is an", "an autosomal", "autosomal recessive", "recessive lysosomal", "lysosomal storage", "storage disorder", "disorder caused", "caused by", "by a", "a deficiency", "deficiency in", "in arylsulfatase", "arylsulfatase b", "n acetyl", "acetyl galactosamine", "galactosamine 4", "4 sulfatase", "mim:611542 .", "611542 .", ". it", "it is", "is named", "named after", "after two", "two french", "french physicians", "pierre maroteaux", "maroteaux and", "and maurice", "maurice emil", "emil joseph", "joseph lamy.", "lamy. maroteaux", "maroteaux first", "first described", "described this", "this disorder", "disorder as", "as a", "a novel", "novel dysostosis", "dysostosis associated", "associated with", "with increased", "increased urinary", "urinary excretion", "excretion of", "of chondroitin", "chondroitin sulfate", "maroteaux et", "et al.", "al. 1963", "1963 .", ". the", "the gene", "gene encoding", "encoding arsb", "arsb is", "is mapped", "mapped to", "to chromosome", "chromosome 5q11", "5q11 q13", "fidzianska et", "al. 1984", "and contains", "contains 8", "8 exons", "exons spanning", "spanning about", "about 206", "206 kb", "karangeorgos et", "al. 2007", "2007 .", ". defective", "defective arsb", "arsb results", "results in", "in build", "build up", "up of", "of dermatan", "dermatan sulfate", "and chondroitin", "in soft", "soft tissues", "tissues causing", "causing compression", "compression and", "and blockages", "blockages in", "in blood", "blood vessels", "corneal clouding", "clouding and", "and disrupting", "disrupting normal", "normal bone", "bone development.", "development. symptoms", "symptoms are", "are similar", "similar to", "to mps", "mps i", "i but", "but with", "with normal", "normal intelligence", "intelligence generally", "rapini et", "valayannopoulos et", "al. 2010", "2010 .", "mucopolysaccharidosis type vi", "vi mps", "syndrome polydystrophic", "dwarfism mim:253200", "mim:253200 is", "253200 is", "is an autosomal", "an autosomal recessive", "autosomal recessive lysosomal", "recessive lysosomal storage", "lysosomal storage disorder", "storage disorder caused", "disorder caused by", "caused by a", "by a deficiency", "a deficiency in", "deficiency in arylsulfatase", "in arylsulfatase b", "b arsb", "arsb n", "n acetyl galactosamine", "acetyl galactosamine 4", "galactosamine 4 sulfatase", "sulfatase mim:611542", "mim:611542 . it", "611542 . it", ". it is", "it is named", "is named after", "named after two", "after two french", "two french physicians", "physicians pierre", "pierre maroteaux and", "maroteaux and maurice", "and maurice emil", "maurice emil joseph", "emil joseph lamy.", "joseph lamy. maroteaux", "lamy. maroteaux first", "maroteaux first described", "first described this", "described this disorder", "this disorder as", "disorder as a", "as a novel", "a novel dysostosis", "novel dysostosis associated", "dysostosis associated with", "associated with increased", "with increased urinary", "increased urinary excretion", "urinary excretion of", "excretion of chondroitin", "of chondroitin sulfate", "sulfate cs", "cs maroteaux", "maroteaux et al.", "et al. 1963", "al. 1963 .", "1963 . the", ". the gene", "the gene encoding", "gene encoding arsb", "encoding arsb is", "arsb is mapped", "is mapped to", "mapped to chromosome", "to chromosome 5q11", "chromosome 5q11 q13", "q13 fidzianska", "fidzianska et al.", "et al. 1984", "1984 and", "and contains 8", "contains 8 exons", "8 exons 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"generally rapini", "rapini et al.", "2007 valayannopoulos", "valayannopoulos et al.", "et al. 2010", "al. 2010 .", "type vi mps", "vi mps vi", "lamy syndrome polydystrophic", "syndrome polydystrophic dwarfism", "polydystrophic dwarfism mim:253200", "mim:253200 is an", "253200 is an", "is an autosomal recessive", "an autosomal recessive lysosomal", "autosomal recessive lysosomal storage", "recessive lysosomal storage disorder", "lysosomal storage disorder caused", "storage disorder caused by", "disorder caused by a", "caused by a deficiency", "by a deficiency in", "a deficiency in arylsulfatase", "deficiency in arylsulfatase b", "arylsulfatase b arsb", "arsb n acetyl", "n acetyl galactosamine 4", "acetyl galactosamine 4 sulfatase", "4 sulfatase mim:611542", "sulfatase mim:611542 .", "mim:611542 . it is", "611542 . it is", ". it is named", "it is named after", "is named after two", "named after two french", "after two french physicians", "french physicians pierre", "physicians pierre maroteaux", "pierre maroteaux and maurice", "maroteaux and maurice emil", "and maurice emil joseph", "maurice emil joseph lamy.", "emil joseph lamy. maroteaux", "joseph lamy. maroteaux first", "lamy. maroteaux first described", "maroteaux first described this", "first described this disorder", "described this disorder as", "this disorder as a", "disorder as a novel", "as a novel dysostosis", "a novel dysostosis associated", "novel dysostosis associated with", "dysostosis associated with increased", "associated with increased urinary", "with increased urinary excretion", "increased urinary excretion of", "urinary excretion of chondroitin", "excretion of chondroitin sulfate", "chondroitin sulfate cs", "cs maroteaux et", "maroteaux et al. 1963", "et al. 1963 .", "al. 1963 . the", "1963 . the gene", ". the gene encoding", "the gene encoding arsb", "gene encoding arsb is", "encoding arsb is mapped", "arsb is mapped to", "is mapped to chromosome", "mapped to chromosome 5q11", "to chromosome 5q11 q13", "5q11 q13 fidzianska", "q13 fidzianska et", "fidzianska et al. 1984", "al. 1984 and", "1984 and contains", "and contains 8 exons", "contains 8 exons spanning", "8 exons spanning about", "exons spanning about 206", "spanning about 206 kb", "206 kb karangeorgos", "kb karangeorgos et", "karangeorgos et al. 2007", "et al. 2007 .", "al. 2007 . defective", "2007 . defective arsb", ". defective arsb results", "defective arsb results in", "arsb results in build", "results in build up", "in build up of", "build up of dermatan", "up of dermatan sulfate", "dermatan sulfate ds", "ds and chondroitin", "cs in soft", "in soft tissues causing", "soft tissues causing compression", "tissues causing compression and", "causing compression and blockages", "compression and blockages in", "and blockages in blood", "blockages in blood vessels", "blood vessels nerves", "trachea corneal clouding", "corneal clouding and disrupting", "clouding and disrupting normal", "and disrupting normal bone", "disrupting normal bone development.", "normal bone development. symptoms", "bone development. symptoms are", "development. symptoms are similar", "symptoms are similar to", "are similar to mps", "similar to mps i", "to mps i but", "mps i but with", "i but with normal", "but with normal intelligence", "with normal intelligence generally", "intelligence generally rapini", "generally rapini et", "rapini et al. 2007", "al. 2007 valayannopoulos", "2007 valayannopoulos et", "valayannopoulos et al. 2010", "et al. 2010 .", "mucopolysaccharidosis type vi mps", "type vi mps vi", "mps vi maroteaux lamy", "vi maroteaux lamy syndrome", "maroteaux lamy syndrome polydystrophic", "lamy syndrome polydystrophic dwarfism", "dwarfism mim:253200 is", "mim:253200 is an autosomal", "253200 is an autosomal", "is an autosomal recessive lysosomal", "an autosomal recessive lysosomal storage", "autosomal recessive lysosomal storage disorder", "recessive lysosomal storage disorder caused", "lysosomal storage disorder caused by", "storage disorder caused by a", "disorder caused by a deficiency", "caused by a deficiency in", "by a deficiency in arylsulfatase", "a deficiency in arylsulfatase b", "in arylsulfatase b arsb", "b arsb n", "arsb n acetyl galactosamine", "n acetyl galactosamine 4 sulfatase", "galactosamine 4 sulfatase mim:611542", "4 sulfatase mim:611542 .", "sulfatase mim:611542 . it", "mim:611542 . it is named", "611542 . it is named", ". it is named after", "it is named after two", "is named after two french", "named after two french physicians", "two french physicians pierre", "french physicians pierre maroteaux", "physicians pierre maroteaux and", "pierre maroteaux and maurice emil", "maroteaux and maurice emil joseph", "and maurice emil joseph lamy.", "maurice emil joseph lamy. maroteaux", "emil joseph lamy. maroteaux first", "joseph lamy. maroteaux first described", "lamy. maroteaux first described this", "maroteaux first described this disorder", "first described this disorder as", "described this disorder as a", "this disorder as a novel", "disorder as a novel dysostosis", "as a novel dysostosis associated", "a novel dysostosis associated with", "novel dysostosis associated with increased", "dysostosis associated with increased urinary", "associated with increased urinary excretion", "with increased urinary excretion of", "increased urinary excretion of chondroitin", "urinary excretion of chondroitin sulfate", "of chondroitin sulfate cs", "sulfate cs maroteaux", "cs maroteaux et al.", "maroteaux et al. 1963 .", "et al. 1963 . the", "al. 1963 . the gene", "1963 . the gene encoding", ". the gene encoding arsb", "the gene encoding arsb is", "gene encoding arsb is mapped", "encoding arsb is mapped to", "arsb is mapped to chromosome", "is mapped to chromosome 5q11", "mapped to chromosome 5q11 q13", "chromosome 5q11 q13 fidzianska", "5q11 q13 fidzianska et", "q13 fidzianska et al.", "et al. 1984 and", "al. 1984 and contains", "1984 and contains 8", "and contains 8 exons spanning", "contains 8 exons spanning about", "8 exons spanning about 206", "exons spanning about 206 kb", "about 206 kb karangeorgos", "206 kb karangeorgos et", "kb karangeorgos et al.", "karangeorgos et al. 2007 .", "et al. 2007 . defective", "al. 2007 . defective arsb", "2007 . defective arsb results", ". defective arsb results in", "defective arsb results in build", "arsb results in build up", "results in build up of", "in build up of dermatan", "build up of dermatan sulfate", "of dermatan sulfate ds", "sulfate ds and", "ds and chondroitin sulfate", "and chondroitin sulfate cs", "sulfate cs in", "cs in soft tissues", "in soft tissues causing compression", "soft tissues causing compression and", "tissues causing compression and blockages", "causing compression and blockages in", "compression and blockages in blood", "and blockages in blood vessels", "in blood vessels nerves", "vessels nerves trachea", "nerves trachea corneal", "trachea corneal clouding and", "corneal clouding and disrupting normal", "clouding and disrupting normal bone", "and disrupting normal bone development.", "disrupting normal bone development. symptoms", "normal bone development. symptoms are", "bone development. symptoms are similar", "development. symptoms are similar to", "symptoms are similar to mps", "are similar to mps i", "similar to mps i but", "to mps i but with", "mps i but with normal", "i but with normal intelligence", "but with normal intelligence generally", "normal intelligence generally rapini", "intelligence generally rapini et", "generally rapini et al.", "et al. 2007 valayannopoulos", "al. 2007 valayannopoulos et", "2007 valayannopoulos et al.", "valayannopoulos et al. 2010 ." ] }, { "record_id": "GLY_000594_1_1328", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206292", "r hsa", "hsa 2206292", "r hsa 2206292" ] }, { "record_id": "GLY_000594_1_1328", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps vii", "sly syndrome", "vii sly", "mps vii sly", "vii sly syndrome", "mucopolysaccharidosis type", "type vii", "beta glucuronidase", "glucuronidase deficiency", "is an", "an autosomal", "autosomal recessive", "recessive lysosomal", "lysosomal storage", "storage disease", "disease characterized", "characterized by", "by a", "a deficiency", "deficiency of", "of the", "the enzyme", "enzyme beta", "which would", "would normally", "normally cleave", "cleave glucuronide", "glucuronide residues", "residues from", "from dematan", "dematan sulphate", "keratan sulphate", "sulphate and", "and chondroitin", "chondroitin sulphate", "resulting in", "in build", "build up", "up of", "of these", "these gags", "gags in", "in cells", "cells and", "and tissues", "sly et", "et al.", "al. 1973", "1973 .", ". the", "the gene", "gene encoding", "encoding gusb", "gusb is", "is 21", "21 kb", "kb long", "contains 12", "12 exons", "exons and", "and gives", "gives rise", "rise to", "to two", "two different", "different types", "types of", "of cdnas", "through an", "an alternate", "alternate splicing", "splicing mechanism", "miller et", "al. 1990", "1990 .", ". it", "it maps", "maps to", "to 7q11.21", "7q11.21 q11.22", "speleman et", "al. 1996", "1996 .", "the phenotype", "phenotype is", "is highly", "highly variable", "ranging from", "from severe", "severe causing", "causing death", "non immune", "immune hydrops", "hydrops fetalis", "vervoort et", "to mild", "mild forms", "forms with", "with survival", "survival into", "into adulthood", "storch et", "al. 2003", "2003 .", ". most", "most patients", "patients with", "with the", "the intermediate", "intermediate phenotype", "phenotype show", "show hepatomegaly", "skeletal anomalies", "coarse facies", "and variable", "variable degrees", "degrees of", "of mental", "mental impairment", "shipley et", "al. 1993", "tomatsu et", "al. 2009", "2009 .", "mucopolysaccharidosis type vii", "vii mps", "syndrome beta", "beta glucuronidase deficiency", "deficiency mim:253220", "mim:253220 is", "253220 is", "is an autosomal", "an autosomal recessive", "autosomal recessive lysosomal", "recessive lysosomal storage", "lysosomal storage disease", "storage disease characterized", "disease characterized by", "characterized by a", "by a deficiency", "a deficiency of", "deficiency of the", "of the enzyme", "the enzyme beta", "enzyme beta glucuronidase", "glucuronidase gusb", "gusb mim:611499", "mim:611499 which", "611499 which", "which would normally", "would normally cleave", "normally cleave glucuronide", "cleave glucuronide residues", "glucuronide residues from", "residues from dematan", "from dematan sulphate", "sulphate keratan", "keratan sulphate and", "sulphate and chondroitin", "and chondroitin sulphate", "sulphate resulting", "resulting in build", "in build up", "build up of", "up of these", "of these gags", "these gags in", "gags in cells", "in cells and", "cells and tissues", "tissues sly", "sly et al.", "et al. 1973", "al. 1973 .", "1973 . the", ". the gene", "the gene encoding", "gene encoding gusb", "encoding gusb is", "gusb is 21", "is 21 kb", "21 kb long", "long contains", "contains 12 exons", "12 exons and", "exons and gives", "and gives rise", "gives rise to", "rise to two", "to two different", "two different types", "different types of", "types of cdnas", "cdnas through", "through an alternate", "an alternate splicing", "alternate splicing mechanism", "mechanism miller", "miller et al.", "et al. 1990", "al. 1990 .", "1990 . it", ". it maps", "it maps to", "maps to 7q11.21", "to 7q11.21 q11.22", "q11.22 speleman", "speleman et al.", "et al. 1996", "al. 1996 .", "1996 . the", ". the phenotype", "the phenotype is", "phenotype is highly", "is highly variable", "variable ranging", "ranging from severe", "from severe causing", "severe causing death", "death non", "non immune hydrops", "immune hydrops fetalis", "fetalis vervoort", "vervoort et al.", "1996 to", "to mild forms", "mild forms with", "forms with survival", "with survival into", "survival into adulthood", "adulthood storch", "storch et al.", "et al. 2003", "al. 2003 .", "2003 . most", ". most patients", "most patients with", "patients with the", "with the intermediate", "the intermediate phenotype", "intermediate phenotype show", "phenotype show hepatomegaly", "hepatomegaly skeletal", "anomalies coarse", "facies and", "and variable degrees", "variable degrees of", "degrees of mental", "of mental impairment", "impairment shipley", "shipley et al.", "et al. 1993", "1993 tomatsu", "tomatsu et al.", "et al. 2009", "al. 2009 .", "type vii mps", "vii mps vii", "sly syndrome beta", "syndrome beta glucuronidase", "glucuronidase deficiency mim:253220", "mim:253220 is an", "253220 is an", "is an autosomal recessive", "an autosomal recessive lysosomal", "autosomal recessive lysosomal storage", "recessive lysosomal storage disease", "lysosomal storage disease characterized", "storage disease characterized by", "disease characterized by a", "characterized by a deficiency", "by a deficiency of", "a deficiency of the", "deficiency of the enzyme", "of the enzyme beta", "the enzyme beta glucuronidase", "beta glucuronidase gusb", "mim:611499 which would", "611499 which would", "which would normally cleave", "would normally cleave glucuronide", "normally cleave glucuronide residues", "cleave glucuronide residues from", "glucuronide residues from dematan", "residues from dematan sulphate", "dematan sulphate keratan", "sulphate keratan sulphate", "keratan sulphate and chondroitin", "sulphate and chondroitin sulphate", "chondroitin sulphate resulting", "sulphate resulting in", "resulting in build up", "in build up of", "build up of these", "up of these gags", "of these gags in", "these gags in cells", "gags in cells and", "in cells and tissues", "and tissues sly", "tissues sly et", "sly et al. 1973", "et al. 1973 .", "al. 1973 . the", "1973 . the gene", ". the gene encoding", "the gene encoding gusb", "gene encoding gusb is", "encoding gusb is 21", "gusb is 21 kb", "is 21 kb long", "kb long contains", "long contains 12", "contains 12 exons and", "12 exons and gives", "exons and gives rise", "and gives rise to", "gives rise to two", "rise to two different", "to two different types", "two different types of", "different types of cdnas", "of cdnas through", "cdnas through an", "through an alternate splicing", "an alternate splicing mechanism", "splicing mechanism miller", "mechanism miller et", "miller et al. 1990", "et al. 1990 .", "al. 1990 . it", "1990 . it maps", ". it maps to", "it maps to 7q11.21", "maps to 7q11.21 q11.22", "7q11.21 q11.22 speleman", "q11.22 speleman et", "speleman et al. 1996", "et al. 1996 .", "al. 1996 . the", "1996 . the phenotype", ". the phenotype is", "the phenotype is highly", "phenotype is highly variable", "highly variable ranging", "variable ranging from", "ranging from severe causing", "from severe causing death", "causing death non", "death non immune", "non immune hydrops fetalis", "hydrops fetalis vervoort", "fetalis vervoort et", "vervoort et al. 1996", "al. 1996 to", "1996 to mild", "to mild forms with", "mild forms with survival", "forms with survival into", "with survival into adulthood", "into adulthood storch", "adulthood storch et", "storch et al. 2003", "et al. 2003 .", "al. 2003 . most", "2003 . most patients", ". most patients with", "most patients with the", "patients with the intermediate", "with the intermediate phenotype", "the intermediate phenotype show", "intermediate phenotype show hepatomegaly", "show hepatomegaly skeletal", "hepatomegaly skeletal anomalies", "skeletal anomalies coarse", "anomalies coarse facies", "coarse facies and", "facies and variable", "and variable degrees of", "variable degrees of mental", "degrees of mental impairment", "mental impairment shipley", "impairment shipley et", "shipley et al. 1993", "al. 1993 tomatsu", "1993 tomatsu et", "tomatsu et al. 2009", "et al. 2009 .", "mucopolysaccharidosis type vii mps", "type vii mps vii", "mps vii sly syndrome", "sly syndrome beta glucuronidase", "syndrome beta glucuronidase deficiency", "beta glucuronidase deficiency mim:253220", "deficiency mim:253220 is", "mim:253220 is an autosomal", "253220 is an autosomal", "is an autosomal recessive lysosomal", "an autosomal recessive lysosomal storage", "autosomal recessive lysosomal storage disease", "recessive lysosomal storage disease characterized", "lysosomal storage disease characterized by", "storage disease characterized by a", "disease characterized by a deficiency", "characterized by a deficiency of", "by a deficiency of the", "a deficiency of the enzyme", "deficiency of the enzyme beta", "of the enzyme beta glucuronidase", "enzyme beta glucuronidase gusb", "glucuronidase gusb mim:611499", "gusb mim:611499 which", "mim:611499 which would normally", "611499 which would normally", "which would normally cleave glucuronide", "would normally cleave glucuronide residues", "normally cleave glucuronide residues from", "cleave glucuronide residues from dematan", "glucuronide residues from dematan sulphate", "from dematan sulphate keratan", "dematan sulphate keratan sulphate", "sulphate keratan sulphate and", "keratan sulphate and chondroitin sulphate", "and chondroitin sulphate resulting", "chondroitin sulphate resulting in", "sulphate resulting in build", "resulting in build up of", "in build up of these", "build up of these gags", "up of these gags in", "of these gags in cells", "these gags in cells and", "gags in cells and tissues", "cells and tissues sly", "and tissues sly et", "tissues sly et al.", "sly et al. 1973 .", "et al. 1973 . the", "al. 1973 . the gene", "1973 . the gene encoding", ". the gene encoding gusb", "the gene encoding gusb is", "gene encoding gusb is 21", "encoding gusb is 21 kb", "gusb is 21 kb long", "21 kb long contains", "kb long contains 12", "long contains 12 exons", "contains 12 exons and gives", "12 exons and gives rise", "exons and gives rise to", "and gives rise to two", "gives rise to two different", "rise to two different types", "to two different types of", "two different types of cdnas", "types of cdnas through", "of cdnas through an", "cdnas through an alternate", "through an alternate splicing mechanism", "alternate splicing mechanism miller", "splicing mechanism miller et", "mechanism miller et al.", "miller et al. 1990 .", "et al. 1990 . it", "al. 1990 . it maps", "1990 . it maps to", ". it maps to 7q11.21", "it maps to 7q11.21 q11.22", "to 7q11.21 q11.22 speleman", "7q11.21 q11.22 speleman et", "q11.22 speleman et al.", "speleman et al. 1996 .", "et al. 1996 . the", "al. 1996 . the phenotype", "1996 . the phenotype is", ". the phenotype is highly", "the phenotype is highly variable", "is highly variable ranging", "highly variable ranging from", "variable ranging from severe", "ranging from severe causing death", "severe causing death non", "causing death non immune", "death non immune hydrops", "immune hydrops fetalis vervoort", "hydrops fetalis vervoort et", "fetalis vervoort et al.", "et al. 1996 to", "al. 1996 to mild", "1996 to mild forms", "to mild forms with survival", "mild forms with survival into", "forms with survival into adulthood", "survival into adulthood storch", "into adulthood storch et", "adulthood storch et al.", "storch et al. 2003 .", "et al. 2003 . most", "al. 2003 . most patients", "2003 . most patients with", ". most patients with the", "most patients with the intermediate", "patients with the intermediate phenotype", "with the intermediate phenotype show", "the intermediate phenotype show hepatomegaly", "phenotype show hepatomegaly skeletal", "show hepatomegaly skeletal anomalies", "skeletal anomalies coarse facies", "coarse facies and variable", "facies and variable degrees", "and variable degrees of mental", "variable degrees of mental impairment", "of mental impairment shipley", "mental impairment shipley et", "impairment shipley et al.", "et al. 1993 tomatsu", "al. 1993 tomatsu et", "1993 tomatsu et al.", "tomatsu et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1329", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206296", "r hsa", "hsa 2206296", "r hsa 2206296" ] }, { "record_id": "GLY_000594_1_1329", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps ii", "hunter syndrome", "ii hunter", "mps ii hunter", "ii hunter syndrome", "mucopolysaccharidosis ii", "is an", "an x", "x linked", "recessive genetic", "genetic disorder", "disorder which", "which therefore", "therefore primarily", "primarily affects", "affects males.", "males. mps", "ii was", "was first", "first described", "described in", "in 1917", "by major", "major charles", "charles hunter", "hunter 1917", "and is", "is caused", "caused by", "by a", "a deficiency", "or absence", "of iduronate", "iduronate 2", "2 sulfatase", "which would", "would normally", "normally hydrolyse", "hydrolyse the", "the 2", "2 sulfate", "sulfate groups", "groups of", "of the", "the l", "l iduronate", "sulfate units", "units of", "of dermatan", "dermatan sulfate", "heparan sulfate", "sulfate and", "and heparin.", "heparin. without", "without ids", "these gags", "gags accumulate", "accumulate in", "in the", "the body", "body and", "and are", "are excessively", "excessively excreted", "excreted in", "in urine.", "urine. although", "although the", "the disease", "disease was", "was known", "known since", "since the", "the early", "early 1970s", "being the", "the first", "first mps", "mps to", "to be", "be defined", "defined clinically", "clinically in", "in humans", "it wasn't", "wasn't until", "until the", "the 1990s", "1990s that", "that ids", "ids was", "was cloned.", "cloned. it", "it is", "is now", "now known", "known to", "be localized", "localized to", "to xq28", "wilson et", "et al.", "al. 1991", "and contain", "contain 9", "9 exons", "flomen et", "al. 1993", "spanning approximately", "approximately 24", "24 kb", "1993 .
              build", ".
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the", "retardation . the rate", ". the rate of", "the rate of progression", "rate of progression and", "of progression and degree", "progression and degree of", "and degree of severity", "degree of severity of", "of severity of the", "severity of the disorder", "of the disorder can", "the disorder can be", "disorder can be different", "can be different for", "be different for each", "different for each person", "for each person with", "each person with mps", "person with mps ii.", "with mps ii. severe", "mps ii. severe forms", "ii. severe forms of", "severe forms of the", "forms of the disorder", "the disorder can result", "disorder can result in", "can result in death", "result in death in", "in death in childhood", "death in childhood whereas", "in childhood whereas those", "childhood whereas those with", "whereas those with a", "those with a \\milder\\", "with a \\milder\\ form", "a \\milder\\ form can", "\\milder\\ form can expect", "form can expect to", "can expect to live", "expect to live to", "to live to their", "live to their 20's", "to their 20's or", "their 20's or 30's.", "30's. some", "some patients even survive", "patients even survive into", "even survive into their", "survive into their fifth", "into their fifth and", "their fifth and sixth", "fifth and sixth decades", "and sixth decades of", "sixth decades of life", "of life wraith", "life wraith et", "wraith et al. 2008", "al. 2008 beck", "2008 beck 2011", "mucopolysaccharidosis ii mps ii", "mps ii hunter syndrome", "syndrome mim:309900 is", "mim:309900 is an x", "309900 is an x", "an x linked recessive", "x linked recessive genetic", "linked recessive genetic disorder", "recessive genetic disorder which therefore", "genetic disorder which therefore primarily", "disorder which therefore primarily affects", "which therefore primarily affects males.", "therefore primarily affects males. mps", "primarily affects males. mps ii", "affects males. mps ii was", "males. mps ii was first", "mps ii was first described", "ii was first described in", "was first described in 1917", "described in 1917 by", "in 1917 by major", "1917 by major charles", "major charles hunter hunter", "charles hunter hunter 1917", "hunter 1917 and is", "1917 and is caused", "and is caused by a", "is caused by a deficiency", "by a deficiency or", "a deficiency or absence", "or absence of iduronate", "absence of iduronate 2", "iduronate 2 sulfatase ids", "sulfatase ids mim:300823", "mim:300823 which would", "300823 which would", "which would normally hydrolyse the", "would normally hydrolyse the 2", "normally hydrolyse the 2 sulfate", "hydrolyse the 2 sulfate groups", "the 2 sulfate groups of", "2 sulfate groups of the", "sulfate groups of the l", "groups of the l iduronate", "of the l iduronate 2", "the l iduronate 2 sulfate", "l iduronate 2 sulfate units", "iduronate 2 sulfate units of", "2 sulfate units of dermatan", "sulfate units of dermatan sulfate", "of dermatan sulfate heparan", "dermatan sulfate heparan sulfate", "sulfate heparan sulfate and", "heparan sulfate and heparin. without", "sulfate and heparin. without ids", "heparin. without ids these", "without ids these gags", "ids these gags accumulate", "these gags accumulate in the", "gags accumulate in the body", "accumulate in the body and", "in the body and are", "the body and are excessively", "body and are excessively excreted", "and are excessively excreted in", "are excessively excreted in urine.", "excessively excreted in urine. although", "excreted in urine. although the", "in urine. although the disease", "urine. although the disease was", "although the disease was known", "the disease was known since", "disease was known since the", "was known since the early", "known since the early 1970s", "the early 1970s being", "early 1970s being the", "1970s being the first", "being the first mps to", "the first mps to be", "first mps to be defined", "mps to be defined clinically", "to be defined clinically in", "be defined 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"GLY_000594_1_1330", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206305", "r hsa", "hsa 2206305", "r hsa 2206305" ] }, { "record_id": "GLY_000594_1_1330", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps iiid", "sanfilippo syndrome", "syndrome d", "sanfilippo syndrome d", "iiid sanfilippo", "mps iiid sanfilippo", "iiid sanfilippo syndrome", "mucopolysaccharidosis iii", "was described", "described in", "in 1963", "1963 by", "by a", "a pediatrician", "pediatrician named", "named sylvester", "sylvester sanfilippo", "j. pediat.", "pediat. 63:", "63: 837", "837 838", "no reference", "reference .", ". mucopolysaccharidosis", "mucopolysaccharidosis type", "type iiid", "is an", "an autosomal", "autosomal recessive", "recessive genetic", "genetic disorder", "disorder due", "due to", "to the", "the loss", "loss of", "of n", "n acetyl", "acetyl d", "d glucosamine", "glucosamine 6", "6 sulfatase", "that hydrolyses", "hydrolyses the", "the 6", "6 sulfate", "sulfate groups", "groups of", "of the", "the n", "sulfate units", "units of", "the glycosaminoglycans", "heparan sulfate", "sulfate and", "and keratan", "keratan sulfate.", "sulfate. gns", "gns is", "is localized", "localized to", "to chromosome", "chromosome 12q14", "12q14 and", "and has", "has 14", "14 exons", "exons spanning", "spanning 46", "46 kb", "robertson et", "et al.", "al. 1988", "mok et", "al. 2003", "2003 .", ". loss", "of enzyme", "enzyme activity", "activity leads", "leads to", "to lysosomal", "lysosomal accumulation", "accumulation and", "and urinary", "urinary excretion", "excretion of", "and n", "n acetylglucosamine", "acetylglucosamine 6", "sulfate residues", ". keratan", "keratan sulphate", "sulphate does", "does not", "not accumulate", "accumulate in", "in mps", "as beta", "beta linked", "linked n", "6 sulphate", "sulphate can", "can be", "be cleaved", "cleaved by", "by beta", "beta hexosaminidase", "hexosaminidase a", "kresse et", "al. 1980", "1980 .", ". this", "this disorder", "disorder is", "is characterized", "characterized by", "by progressive", "progressive mental", "mental deterioration", "deterioration but", "but only", "only moderate", "moderate physical", "physical abnormalities", "abnormalities and", "and death", "death duing", "duing the", "the second", "second or", "or third", "third decade", "decade of", "of life", "presenting a", "a phenotype", "phenotype similar", "similar to", "to mpsiiia", "jones et", "al. 1997", "de ruijter", "ruijter et", "al. 2011", "2011 .", "iii sanfilippo", "syndrome was", "was described in", "described in 1963", "in 1963 by", "1963 by a", "by a pediatrician", "a pediatrician named", "pediatrician named sylvester", "named sylvester sanfilippo", "sanfilippo j.", "j. pediat. 63:", "pediat. 63: 837", "63: 837 838", "838 1963", "1963 no", "no reference .", "reference . mucopolysaccharidosis", ". mucopolysaccharidosis type", "mucopolysaccharidosis type iiid", "iiid mps", "d mim:252940", "mim:252940 is", "252940 is", "is an autosomal", "an autosomal recessive", "autosomal recessive genetic", "recessive genetic disorder", "genetic disorder due", "disorder due to", "due to the", "to the loss", "the loss of", "loss of n", "of n acetyl", "n acetyl d", "acetyl d glucosamine", "d glucosamine 6", "glucosamine 6 sulfatase", "sulfatase gns", "gns mim:607664", "that hydrolyses the", "hydrolyses the 6", "the 6 sulfate", "6 sulfate groups", "sulfate groups of", "groups of the", "of the n", "the n acetyl", "glucosamine 6 sulfate", "6 sulfate units", "sulfate units of", "units of the", "of the glycosaminoglycans", "glycosaminoglycans gags", "gags heparan", "heparan sulfate and", "sulfate and keratan", "and keratan sulfate.", "keratan sulfate. gns", "sulfate. gns is", "gns is localized", "is localized to", "localized to chromosome", "to chromosome 12q14", "chromosome 12q14 and", "12q14 and has", "and has 14", "has 14 exons", "14 exons spanning", "exons spanning 46", "spanning 46 kb", "kb robertson", "robertson et al.", "et al. 1988", "1988 mok", "mok et al.", "et al. 2003", "al. 2003 .", "2003 . loss", ". loss of", "loss of enzyme", "of enzyme activity", "enzyme activity leads", "activity leads to", "leads to lysosomal", "to lysosomal accumulation", "lysosomal accumulation and", "accumulation and urinary", "and urinary excretion", "urinary excretion of", "of heparan", "sulfate and n", "and n acetylglucosamine", "n acetylglucosamine 6", "acetylglucosamine 6 sulfate", "6 sulfate residues", "residues mok", "2003 . keratan", ". keratan sulphate", "keratan sulphate does", "sulphate does not", "does not accumulate", "not accumulate in", "accumulate in mps", "in mps iiid", "iiid as", "as beta linked", "beta linked n", "linked n acetyl", "glucosamine 6 sulphate", "6 sulphate can", "sulphate can be", "can be cleaved", "be cleaved by", "cleaved by beta", "by beta hexosaminidase", "beta hexosaminidase a", "a kresse", "kresse et al.", "et al. 1980", "al. 1980 .", "1980 . this", ". this disorder", "this disorder is", "disorder is characterized", "is characterized by", "characterized by progressive", "by progressive mental", "progressive mental deterioration", "mental deterioration but", "deterioration but only", "but only moderate", "only moderate physical", "moderate physical abnormalities", "physical abnormalities and", "abnormalities and death", "and death duing", "death duing the", "duing the second", "the second or", "second or third", "or third decade", "third decade of", "decade of life", "life presenting", "presenting a phenotype", "a phenotype similar", "phenotype similar to", "similar to mpsiiia", "mpsiiia jones", "jones et al.", "et al. 1997", "1997 de", "de ruijter et", "ruijter et al.", "et al. 2011", "al. 2011 .", "mucopolysaccharidosis iii sanfilippo", "iii sanfilippo syndrome", "sanfilippo syndrome was", "syndrome was described", "was described in 1963", "described in 1963 by", "in 1963 by a", "1963 by a pediatrician", "by a pediatrician named", "a pediatrician named sylvester", "pediatrician named sylvester sanfilippo", "sylvester sanfilippo j.", "sanfilippo j. pediat.", "j. pediat. 63: 837", "pediat. 63: 837 838", "837 838 1963", "1963 no reference", "no reference . mucopolysaccharidosis", "reference . mucopolysaccharidosis type", ". mucopolysaccharidosis type iiid", "type iiid mps", "iiid mps iiid", "syndrome d mim:252940", "mim:252940 is an", "252940 is an", "is an autosomal recessive", "an autosomal recessive genetic", "autosomal recessive genetic disorder", "recessive genetic disorder due", "genetic disorder due to", "disorder due to the", "due to the loss", "to the loss of", "the loss of n", "loss of n acetyl", "of n acetyl d", "n acetyl d glucosamine", "acetyl d glucosamine 6", "d glucosamine 6 sulfatase", "6 sulfatase gns", "mim:607664 that", "607664 that", "that hydrolyses the 6", "hydrolyses the 6 sulfate", "the 6 sulfate groups", "6 sulfate groups of", "sulfate groups of the", "groups of the n", "of the n acetyl", "the n acetyl d", "d glucosamine 6 sulfate", "glucosamine 6 sulfate units", "6 sulfate units of", "sulfate units of the", "units of the glycosaminoglycans", "the glycosaminoglycans gags", "gags heparan sulfate", "heparan sulfate and keratan", "sulfate and keratan sulfate.", "and keratan sulfate. gns", "keratan sulfate. gns is", "sulfate. gns is localized", "gns is localized to", "is localized to chromosome", "localized to chromosome 12q14", "to chromosome 12q14 and", "chromosome 12q14 and has", "12q14 and has 14", "and has 14 exons", "has 14 exons spanning", "14 exons spanning 46", "exons spanning 46 kb", "46 kb robertson", "kb robertson et", "robertson et al. 1988", "al. 1988 mok", "1988 mok et", "mok et al. 2003", "et al. 2003 .", "al. 2003 . loss", "2003 . loss of", ". loss of enzyme", "loss of enzyme activity", "of enzyme activity leads", "enzyme activity leads to", "activity leads to lysosomal", "leads to lysosomal accumulation", "to lysosomal accumulation and", "lysosomal accumulation and urinary", "accumulation and urinary excretion", "and urinary excretion of", "excretion of heparan", "of heparan sulfate", "heparan sulfate and n", "sulfate and n acetylglucosamine", "and n acetylglucosamine 6", "n acetylglucosamine 6 sulfate", "acetylglucosamine 6 sulfate residues", "sulfate residues mok", "residues mok et", "al. 2003 . keratan", "2003 . keratan sulphate", ". keratan sulphate does", "keratan sulphate does not", "sulphate does not accumulate", "does not accumulate in", "not accumulate in mps", "accumulate in mps iiid", "mps iiid as", "iiid as beta", "as beta linked n", "beta linked n acetyl", "linked n acetyl d", "d glucosamine 6 sulphate", "glucosamine 6 sulphate can", "6 sulphate can be", "sulphate can be cleaved", "can be cleaved by", "be cleaved by beta", "cleaved by beta hexosaminidase", "by beta hexosaminidase a", "hexosaminidase a kresse", "a kresse et", "kresse et al. 1980", "et al. 1980 .", "al. 1980 . this", "1980 . this disorder", ". this disorder is", "this disorder is characterized", "disorder is characterized by", "is characterized by progressive", "characterized by progressive mental", "by progressive mental deterioration", "progressive mental deterioration but", "mental deterioration but only", "deterioration but only moderate", "but only moderate physical", "only moderate physical abnormalities", "moderate physical abnormalities and", "physical abnormalities and death", "abnormalities and death duing", "and death duing the", "death duing the second", "duing the second or", "the second or third", "second or third decade", "or third decade of", "third decade of life", "of life presenting", "life presenting a", "presenting a phenotype similar", "a phenotype similar to", "phenotype similar to mpsiiia", "to mpsiiia jones", "mpsiiia jones et", "jones et al. 1997", "al. 1997 de", "1997 de ruijter", "de ruijter et al.", "ruijter et al. 2011", "et al. 2011 .", "mucopolysaccharidosis iii sanfilippo syndrome", "sanfilippo syndrome was described", "syndrome was described in", "was described in 1963 by", "described in 1963 by a", "in 1963 by a pediatrician", "1963 by a pediatrician named", "by a pediatrician named sylvester", "a pediatrician named sylvester sanfilippo", "named sylvester sanfilippo j.", "sylvester sanfilippo j. pediat.", "sanfilippo j. pediat. 63:", "j. pediat. 63: 837 838", "63: 837 838 1963", "838 1963 no", "1963 no reference .", "no reference . mucopolysaccharidosis type", "reference . mucopolysaccharidosis type iiid", "mucopolysaccharidosis type iiid mps", "type iiid mps iiid", "mps iiid sanfilippo syndrome", "iiid sanfilippo syndrome d", "sanfilippo syndrome d mim:252940", "d mim:252940 is", "mim:252940 is an autosomal", "252940 is an autosomal", "is an autosomal recessive genetic", "an autosomal recessive genetic disorder", "autosomal recessive genetic disorder due", "recessive genetic disorder due to", "genetic disorder due to the", "disorder due to the loss", "due to the loss of", "to the loss of n", "the loss of n acetyl", "loss of n acetyl d", "of n acetyl d glucosamine", "n acetyl d glucosamine 6", "acetyl d glucosamine 6 sulfatase", "glucosamine 6 sulfatase gns", "sulfatase gns mim:607664", "mim:607664 that hydrolyses", "607664 that hydrolyses", "that hydrolyses the 6 sulfate", "hydrolyses the 6 sulfate groups", "the 6 sulfate groups of", "6 sulfate groups of the", "sulfate groups of the n", "groups of the n acetyl", "of the n acetyl d", "the n acetyl d glucosamine", "acetyl d glucosamine 6 sulfate", "d glucosamine 6 sulfate units", "glucosamine 6 sulfate units of", "6 sulfate units of the", "sulfate units of the glycosaminoglycans", "of the glycosaminoglycans gags", "glycosaminoglycans gags heparan", "gags heparan sulfate and", "heparan sulfate and keratan sulfate.", "sulfate and keratan sulfate. gns", "and keratan sulfate. gns is", "keratan sulfate. gns is localized", "sulfate. gns is localized to", "gns is localized to chromosome", "is localized to chromosome 12q14", "localized to chromosome 12q14 and", "to chromosome 12q14 and has", "chromosome 12q14 and has 14", "12q14 and has 14 exons", "and has 14 exons spanning", "has 14 exons spanning 46", "14 exons spanning 46 kb", "spanning 46 kb robertson", "46 kb robertson et", "kb robertson et al.", "et al. 1988 mok", "al. 1988 mok et", "1988 mok et al.", "mok et al. 2003 .", "et al. 2003 . loss", "al. 2003 . loss of", "2003 . loss of enzyme", ". loss of enzyme activity", "loss of enzyme activity leads", "of enzyme activity leads to", "enzyme activity leads to lysosomal", "activity leads to lysosomal accumulation", "leads to lysosomal accumulation and", "to lysosomal accumulation and urinary", "lysosomal accumulation and urinary excretion", "accumulation and urinary excretion of", "urinary excretion of heparan", "excretion of heparan sulfate", "of heparan sulfate and", "heparan sulfate and n acetylglucosamine", "sulfate and n acetylglucosamine 6", "and n acetylglucosamine 6 sulfate", "n acetylglucosamine 6 sulfate residues", "6 sulfate residues mok", "sulfate residues mok et", "residues mok et al.", "et al. 2003 . keratan", "al. 2003 . keratan sulphate", "2003 . keratan sulphate does", ". keratan sulphate does not", "keratan sulphate does not accumulate", "sulphate does not accumulate in", "does not accumulate in mps", "not accumulate in mps iiid", "in mps iiid as", "mps iiid as beta", "iiid as beta linked", "as beta linked n acetyl", "beta linked n acetyl d", "linked n acetyl d glucosamine", "acetyl d glucosamine 6 sulphate", "d glucosamine 6 sulphate can", "glucosamine 6 sulphate can be", "6 sulphate can be cleaved", "sulphate can be cleaved by", "can be cleaved by beta", "be cleaved by beta hexosaminidase", "cleaved by beta hexosaminidase a", "beta hexosaminidase a kresse", "hexosaminidase a kresse et", "a kresse et al.", "kresse et al. 1980 .", "et al. 1980 . this", "al. 1980 . this disorder", "1980 . this disorder is", ". this disorder is characterized", "this disorder is characterized by", "disorder is characterized by progressive", "is characterized by progressive mental", "characterized by progressive mental deterioration", "by progressive mental deterioration but", "progressive mental deterioration but only", "mental deterioration but only moderate", "deterioration but only moderate physical", "but only moderate physical abnormalities", "only moderate physical abnormalities and", "moderate physical abnormalities and death", "physical abnormalities and death duing", "abnormalities and death duing the", "and death duing the second", "death duing the second or", "duing the second or third", "the second or third decade", "second or third decade of", "or third decade of life", "decade of life presenting", "of life presenting a", "life presenting a phenotype", "presenting a phenotype similar to", "a phenotype similar to mpsiiia", "similar to mpsiiia jones", "to mpsiiia jones et", "mpsiiia jones et al.", "et al. 1997 de", "al. 1997 de ruijter", "1997 de ruijter et", "de ruijter et al. 2011", "ruijter et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1331", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206308", "r hsa", "hsa 2206308", "r hsa 2206308" ] }, { "record_id": "GLY_000594_1_1331", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps iv", "morquio syndrome", "syndrome b", "morquio syndrome b", "iv morquio", "mps iv morquio", "iv morquio syndrome", "defects in", "in beta", "beta galactosidase", "can result", "result in", "in gm1", "gm1 gangliosidosis", "nishimoto et", "et al.", "al. 1991", "not described", "described here", "with several", "several phenotypes", "phenotypes indicating", "indicating mental", "mental deterioration", "as well", "well as", "as in", "in mucopolysaccharidosis", "mucopolysaccharidosis ivb", "a characteristic", "characteristic mucopolysaccharidosis", "mucopolysaccharidosis with", "with no", "no neurological", "neurological symptoms", "callahan 1999", "1999 .

              mucopolysaccharidosis", ".

              mucopolysaccharidosis ivb", "mps ivb", "morquio's syndrome", "is a", "a rare", "autosomal recessive", "recessive mucopolysaccharide", "mucopolysaccharide storage", "storage disease", "disease characterized", "characterized by", "by intracellular", "intracellular accumulation", "accumulation of", "of keratan", "keratan sulfate", "skeletal dysplasia", "dysplasia and", "and corneal", "corneal clouding.", "clouding. there", "there is", "is no", "no central", "central nervous", "nervous system", "system involvement", "intelligence is", "is normal", "normal and", "and there", "is increased", "increased ks", "ks excretion", "excretion in", "in urine", "suzuki et", "al. \\beta", "\\beta galactosidase", "galactosidase deficiency", "beta galactosidosis", "galactosidosis :", ": gm1", "gangliosidosis and", "and morquio", "morquio b", "b disease\\", "p3775 3809", "3809 in", "in stryer", "stryer et", "al. 2001", "2001 .", ". mpsivb", "mpsivb is", "is caused", "caused by", "by a", "a defect", "defect in", "in betagalactosidase", "which normally", "normally cleaves", "cleaves terminal", "terminal galactosyl", "galactosyl residues", "residues from", "from glycosaminoglycans", "gangliosides and", "and glycoproteins.", "glycoproteins. the", "the glb1", "glb1 gene", "gene spans", "spans 62.5", "62.5 kb", "kb and", "and contains", "contains 16", "16 exons", "oshima et", "et al.1988", "santamaria et", "al. 2007", "and maps", "maps to", "to chromosome", "chromosome 3p21.33", "takano &", "& yamanouchi", "yamanouchi 1993", "1993 .
              ", "defects in beta", "in beta galactosidase", "galactosidase glb1", "glb1 mim:611458", "mim:611458 can", "611458 can", "can result in", "result in gm1", "in gm1 gangliosidosis", "gangliosidosis gm1", "gm1 mim:230500", "nishimoto et al.", "et al. 1991", "not described here", "with several phenotypes", "several phenotypes indicating", "phenotypes indicating mental", "indicating mental deterioration", "deterioration as", "as well as", "well as in", "as in mucopolysaccharidosis", "in mucopolysaccharidosis ivb", "ivb a", "a characteristic mucopolysaccharidosis", "characteristic mucopolysaccharidosis with", "mucopolysaccharidosis with no", "with no neurological", "no neurological symptoms", "symptoms callahan", "callahan 1999 .

              mucopolysaccharidosis", "1999 .

              mucopolysaccharidosis ivb", "ivb mps", "ivb morquio's", "morquio's syndrome b", "b mim:253010", "mim:253010 is", "253010 is", "is a rare", "rare autosomal", "autosomal recessive mucopolysaccharide", "recessive mucopolysaccharide storage", "mucopolysaccharide storage disease", "storage disease characterized", "disease characterized by", "characterized by intracellular", "by intracellular accumulation", "intracellular accumulation of", "accumulation of keratan", "of keratan sulfate", "sulfate ks", "skeletal dysplasia and", "dysplasia and corneal", "and corneal clouding.", "corneal clouding. there", "clouding. there is", "there is no", "is no central", "no central nervous", "central nervous system", "nervous system involvement", "involvement intelligence", "intelligence is normal", "is normal and", "normal and there", "and there is", "there is increased", "is increased ks", "increased ks excretion", "ks excretion in", "excretion in urine", "urine suzuki", "suzuki et al.", "et al. \\beta", "al. \\beta galactosidase", "\\beta galactosidase deficiency", "deficiency beta", "beta galactosidosis :", "galactosidosis : gm1", ": gm1 gangliosidosis", "gm1 gangliosidosis and", "gangliosidosis and morquio", "and morquio b", "morquio b disease\\", "disease\\ p3775", "p3775 3809 in", "3809 in stryer", "in stryer et", "stryer et al.", "et al. 2001", "al. 2001 .", "2001 . mpsivb", ". mpsivb is", "mpsivb is caused", "is caused by", "caused by a", "by a defect", "a defect in", "defect in betagalactosidase", "betagalactosidase glb1", "which normally cleaves", "normally cleaves terminal", "cleaves terminal galactosyl", "terminal galactosyl residues", "galactosyl residues from", "residues from glycosaminoglycans", "glycosaminoglycans gangliosides", "gangliosides and glycoproteins.", "and glycoproteins. the", "glycoproteins. the glb1", "the glb1 gene", "glb1 gene spans", "gene spans 62.5", "spans 62.5 kb", "62.5 kb and", "kb and contains", "and contains 16", "contains 16 exons", "exons oshima", "oshima et al.1988", "al.1988 santamaria", "santamaria et al.", "et al. 2007", "2007 and", "and maps to", "maps to chromosome", "to chromosome 3p21.33", "3p21.33 takano", "takano & yamanouchi", "& yamanouchi 1993", "yamanouchi 1993 .
              ", "defects in beta galactosidase", "beta galactosidase glb1", "mim:611458 can result", "611458 can result", "can result in gm1", "result in gm1 gangliosidosis", "gm1 gangliosidosis gm1", "mim:230500 nishimoto", "230500 nishimoto", "nishimoto et al. 1991", "1991 not", "here with", "with several phenotypes indicating", "several phenotypes indicating mental", "phenotypes indicating mental deterioration", "mental deterioration as", "deterioration as well", "as well as in", "well as in mucopolysaccharidosis", "as in mucopolysaccharidosis ivb", "mucopolysaccharidosis ivb a", "ivb a characteristic", "a characteristic mucopolysaccharidosis with", "characteristic mucopolysaccharidosis with no", "mucopolysaccharidosis with no neurological", "with no neurological symptoms", "neurological symptoms callahan", "symptoms callahan 1999", "callahan 1999 .

              mucopolysaccharidosis ivb", ".

              mucopolysaccharidosis ivb mps", "ivb mps ivb", "mps ivb morquio's", "ivb morquio's syndrome", "syndrome b mim:253010", "mim:253010 is a", "253010 is a", "a rare autosomal", "rare autosomal recessive", "autosomal recessive mucopolysaccharide storage", "recessive mucopolysaccharide storage disease", "mucopolysaccharide storage disease characterized", "storage disease characterized by", "disease characterized by intracellular", "characterized by intracellular accumulation", "by intracellular accumulation of", "intracellular accumulation of keratan", "accumulation of keratan sulfate", "keratan sulfate ks", "ks skeletal", "skeletal dysplasia and corneal", "dysplasia and corneal clouding.", "and corneal clouding. there", "corneal clouding. there is", "clouding. there is no", "there is no central", "is no central nervous", "no central nervous system", "central nervous system involvement", "system involvement intelligence", "involvement intelligence is", "intelligence is normal and", "is normal and there", "normal and there is", "and there is increased", "there is increased ks", "is increased ks excretion", "increased ks excretion in", "ks excretion in urine", "in urine suzuki", "urine suzuki et", "suzuki et al. \\beta", "et al. \\beta galactosidase", "al. \\beta galactosidase deficiency", "galactosidase deficiency beta", "deficiency beta galactosidosis", "beta galactosidosis : gm1", "galactosidosis : gm1 gangliosidosis", ": gm1 gangliosidosis and", "gm1 gangliosidosis and morquio", "gangliosidosis and morquio b", "and morquio b disease\\", "b disease\\ p3775", "disease\\ p3775 3809", "p3775 3809 in stryer", "3809 in stryer et", "in stryer et al.", "stryer et al. 2001", "et al. 2001 .", "al. 2001 . mpsivb", "2001 . mpsivb is", ". mpsivb is caused", "mpsivb is caused by", "is caused by a", "caused by a defect", "by a defect in", "a defect in betagalactosidase", "in betagalactosidase glb1", "glb1 which", "which normally cleaves terminal", "normally cleaves terminal galactosyl", "cleaves terminal galactosyl residues", "terminal galactosyl residues from", "galactosyl residues from glycosaminoglycans", "from glycosaminoglycans gangliosides", "glycosaminoglycans gangliosides and", "gangliosides and glycoproteins. the", "and glycoproteins. the glb1", "glycoproteins. the glb1 gene", "the glb1 gene spans", "glb1 gene spans 62.5", "gene spans 62.5 kb", "spans 62.5 kb and", "62.5 kb and contains", "kb and contains 16", "and contains 16 exons", "16 exons oshima", "exons oshima et", "et al.1988 santamaria", "al.1988 santamaria et", "santamaria et al. 2007", "al. 2007 and", "2007 and maps", "and maps to chromosome", "maps to chromosome 3p21.33", "chromosome 3p21.33 takano", "3p21.33 takano &", "takano & yamanouchi 1993", "& yamanouchi 1993 .
              ", "in beta galactosidase glb1", "galactosidase glb1 mim:611458", "glb1 mim:611458 can", "mim:611458 can result in", "611458 can result in", "can result in gm1 gangliosidosis", "in gm1 gangliosidosis gm1", "gangliosidosis gm1 mim:230500", "mim:230500 nishimoto et", "230500 nishimoto et", "al. 1991 not", "1991 not described", "described here with", "here with several", "with several phenotypes indicating mental", "several phenotypes indicating mental deterioration", "indicating mental deterioration as", "mental deterioration as well", "deterioration as well as", "as well as in mucopolysaccharidosis", "well as in mucopolysaccharidosis ivb", "in mucopolysaccharidosis ivb a", "mucopolysaccharidosis ivb a characteristic", "ivb a characteristic mucopolysaccharidosis", "a characteristic mucopolysaccharidosis with no", "characteristic mucopolysaccharidosis with no neurological", "mucopolysaccharidosis with no neurological symptoms", "no neurological symptoms callahan", "neurological symptoms callahan 1999", "symptoms callahan 1999 .

              mucopolysaccharidosis", "1999 .

              mucopolysaccharidosis ivb mps", ".

              mucopolysaccharidosis ivb mps ivb", "mps ivb morquio's syndrome", "ivb morquio's syndrome b", "morquio's syndrome b mim:253010", "b mim:253010 is", "mim:253010 is a rare", "253010 is a rare", "is a rare autosomal", "a rare autosomal recessive", "rare autosomal recessive mucopolysaccharide", "autosomal recessive mucopolysaccharide storage disease", "recessive mucopolysaccharide storage disease characterized", "mucopolysaccharide storage disease characterized by", "storage disease characterized by intracellular", "disease characterized by intracellular accumulation", "characterized by intracellular accumulation of", "by intracellular accumulation of keratan", "intracellular accumulation of keratan sulfate", "of keratan sulfate ks", "ks skeletal dysplasia", "skeletal dysplasia and corneal clouding.", "dysplasia and corneal clouding. there", "and corneal clouding. there is", "corneal clouding. there is no", "clouding. there is no central", "there is no central nervous", "is no central nervous system", "no central nervous system involvement", "nervous system involvement intelligence", "system involvement intelligence is", "involvement intelligence is normal", "intelligence is normal and there", "is normal and there is", "normal and there is increased", "and there is increased ks", "there is increased ks excretion", "is increased ks excretion in", "increased ks excretion in urine", "excretion in urine suzuki", "in urine suzuki et", "urine suzuki et al.", "suzuki et al. \\beta galactosidase", "et al. \\beta galactosidase deficiency", "\\beta galactosidase deficiency beta", "galactosidase deficiency beta galactosidosis", "deficiency beta galactosidosis :", "beta galactosidosis : gm1 gangliosidosis", "galactosidosis : gm1 gangliosidosis and", ": gm1 gangliosidosis and morquio", "gm1 gangliosidosis and morquio b", "gangliosidosis and morquio b disease\\", "morquio b disease\\ p3775", "b disease\\ p3775 3809", "disease\\ p3775 3809 in", "p3775 3809 in stryer et", "3809 in stryer et al.", "in stryer et al. 2001", "stryer et al. 2001 .", "et al. 2001 . mpsivb", "al. 2001 . mpsivb is", "2001 . mpsivb is caused", ". mpsivb is caused by", "mpsivb is caused by a", "is caused by a defect", "caused by a defect in", "by a defect in betagalactosidase", "defect in betagalactosidase glb1", "glb1 which normally", "which normally cleaves terminal galactosyl", "normally cleaves terminal galactosyl residues", "cleaves terminal galactosyl residues from", "terminal galactosyl residues from glycosaminoglycans", "residues from glycosaminoglycans gangliosides", "from glycosaminoglycans gangliosides and", "glycosaminoglycans gangliosides and glycoproteins.", "gangliosides and glycoproteins. the glb1", "and glycoproteins. the glb1 gene", "glycoproteins. the glb1 gene spans", "the glb1 gene spans 62.5", "glb1 gene spans 62.5 kb", "gene spans 62.5 kb and", "spans 62.5 kb and contains", "62.5 kb and contains 16", "kb and contains 16 exons", "contains 16 exons oshima", "16 exons oshima et", "exons oshima et al.1988", "oshima et al.1988 santamaria", "et al.1988 santamaria et", "al.1988 santamaria et al.", "et al. 2007 and", "al. 2007 and maps", "2007 and maps to", "and maps to chromosome 3p21.33", "to chromosome 3p21.33 takano", "chromosome 3p21.33 takano &", "3p21.33 takano & yamanouchi", "takano & yamanouchi 1993 .
              " ] }, { "record_id": "GLY_000594_1_1332", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2395516", "r hsa", "hsa 2395516", "r hsa 2395516" ] }, { "record_id": "GLY_000594_1_1332", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "electron transport", "transport from", "from nadph", "nadph to", "to ferredoxin", "electron transport from", "transport from nadph", "from nadph to", "nadph to ferredoxin", "electron transport from nadph", "transport from nadph to", "from nadph to ferredoxin", "electron transport from nadph to", "transport from nadph to ferredoxin", "ferredoxin reductase", "adrenodoxin reductase", "and ferredoxins", "comprise a", "a short", "short electron", "transport chain", "chain that", "that provides", "provides electrons", "electrons for", "for biosynthesis", "biosynthesis of", "of iron", "iron sulfur", "sulfur clusters", "clusters and", "and steroid", "steroid hormones", "sheftel et", "et al.", "al. 2010", "shi et", "al. 2012", "reviewed in", "in grinberg", "grinberg et", "al. 2000", "lambeth et", "al. 1982", "1982 .", "nadph ferredoxin", "reductase fdxr", "fdxr adrenodoxin", "ferredoxins fdx1", "fdx1 fdx1l", "fdx1l comprise", "comprise a short", "a short electron", "short electron transport", "electron transport chain", "transport chain that", "chain that provides", "that provides electrons", "provides electrons for", "electrons for biosynthesis", "for biosynthesis of", "biosynthesis of iron", "of iron sulfur", "iron sulfur clusters", "sulfur clusters and", "clusters and steroid", "and steroid hormones", "hormones sheftel", "sheftel et al.", "et al. 2010", "2010 shi", "shi et al.", "et al. 2012", "2012 reviewed", "reviewed in grinberg", "in grinberg et", "grinberg et al.", "et al. 2000", "2000 lambeth", "lambeth et al.", "et al. 1982", "al. 1982 .", "nadph ferredoxin reductase", "ferredoxin reductase fdxr", "fdxr adrenodoxin reductase", 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"senescence associated", "associated heterochromatin", "heterochromatin foci", "formation of senescence", "of senescence associated", "senescence associated heterochromatin", "associated heterochromatin foci", "foci sahf", "formation of senescence associated", "of senescence associated heterochromatin", "senescence associated heterochromatin foci", "heterochromatin foci sahf", "formation of senescence associated heterochromatin", "of senescence associated heterochromatin foci", "associated heterochromatin foci sahf", "the process", "process of", "of dna", "dna damage/telomere", "damage/telomere stress", "stress induced", "induced senescence", "senescence culminates", "culminates in", "in the", "the formation", "sahf .", ". these", "these foci", "foci represent", "represent facultative", "facultative heterochromatin", "heterochromatin that", "that is", "is formed", "formed in", "in senescent", "senescent cells.", "cells. they", "they contribute", "contribute to", "to the", "the repression", "repression of", "of proliferation", "proliferation promoting", "promoting genes", "genes and", "and play", "play an", "an important", "important role", "role in", "the permanent", "permanent cell", "cell cycle", "cycle exit", "exit that", "that characterizes", "characterizes senescence", "narita et", "et al.", "al. 2003", "2003 and", "and 2006", "2006 .", ". sahf", "sahf appear", "appear as", "as compacted", "punctate dapi", "dapi stained", "stained foci", "foci of", "of dna.", "dna. each", "each chromosome", "chromosome is", "is condensed", "condensed into", "into a", "a single", "single sah", "sah focus", "with telomeric", "telomeric and", "and centromeric", "centromeric chromatin", "chromatin located", "located predominantly", "predominantly at", "at its", "its periphery", "funayama et", "al. 2006", "zhang et", "al. 2007", "2007 .

              an", ".

              an evolutionarily", "evolutionarily conserved", "conserved protein", "protein complex", "complex of", "of hira", "ubn1 and", "and cabin1", "cabin1 plays", "plays a", "a crucial", "crucial role", "the sahf", "sahf formation.", "formation. as", "as cells", "cells approach", "approach senescence", "cabin1 accumulate", "accumulate at", "at the", "the pml", "pml bodies", "al. 2005", "banumathy et", "al. 2009", "rai et", "al. 2011", "2011 .", ". pml", "bodies are", "are punctate", "punctate nuclear", "nuclear structures", "structures that", "that contain", "contain pml", "pml protein", "protein and", "and numerous", "numerous other", "other proteins", "proteins and", "and are", "are proposed", "proposed to", "to be", "be the", "the sites", "sites of", "of assembly", "assembly of", "of macromolecular", "macromolecular regulatory", "regulatory complexes", "complexes and", "and protein", "protein modification", "fogal et", "al. 2000", "guo et", "pearson et", "2000 .", ". recruitment", "recruitment of", "hira to", "to pml", "bodies coincides", "coincides with", "with altered", "altered chromatin", "chromatin structure", "structure and", "and deposition", "deposition of", "of macroh2a", "macroh2a histone", "histone h2a", "h2a variant", "variant onto", "onto chromatin.", "chromatin. as", "cells become", "become senescent", "cabin1 relocate", "relocate from", "from pml", "bodies to", "to sahf.", "sahf. hira", "hira accumulation", "accumulation at", "at pml", "bodies is", "is rb1", "and tp53", "but may", "may require", "require phosphorylation", "phosphorylation of", "hira serine", "serine s697", "s697 by", "by gsk3b", "kennedy et", "2007 .", "sahf formation", "formation itself", "requires functional", "functional rb1", "rb1 and", "tp53 pathways", "2007 .

              sahf", ".

              sahf contain", "contain h3k9me", "h3k9me mark", "characteristic of", "of trancriptionally", "trancriptionally silent", "silent chromatin", "and hp1", "marcoh2a histone", "variant and", "and hmga", "hmga proteins", "proteins are", "are also", "also components", "components of", "of sahf", "besides the", "the hira:asf1a:ubn1:cabin1", "hira:asf1a:ubn1:cabin1 complex.", "complex. a", "a yet", "yet unidentified", "unidentified h3k9me", "h3k9me histone", "histone methyltransferase", "methyltransferase may", "may be", "be recruited", "recruited to", "to sahf", "sahf by", "by ubn1", "2009 .", ". one", "one of", "of the", "the functions", "functions of", "hira:asf1a:ubn1:cabin1 complex", "complex is", "is to", "to deposit", "deposit histone", "histone h3.3.", "h3.3. variant", "variant to", "to chromatin", "which influences", "influences gene", "gene expression", "2011 .

              further", ".

              further studies", "studies are", "are needed", "needed to", "to fully", "fully elucidate", "elucidate the", "the mechanism", "mechanism of", "formation and", "and mechanism", "mechanism by", "by which", "which sahf", "sahf promote", "promote cell", "cell senescence.", "the process of", "process of dna", "of dna damage/telomere", "dna damage/telomere stress", "damage/telomere stress induced", "stress induced senescence", "induced senescence culminates", "senescence culminates in", "culminates in the", "in the formation", "the formation of", "sahf . these", ". these foci", "these foci represent", "foci represent facultative", "represent facultative heterochromatin", "facultative heterochromatin that", "heterochromatin that is", "that is formed", "is formed in", "formed in senescent", "in senescent cells.", "senescent cells. they", "cells. they contribute", "they contribute to", "contribute to the", "to the repression", "the repression of", "repression of proliferation", "of proliferation promoting", "proliferation promoting genes", "promoting genes and", "genes and play", "and play an", "play an important", "an important role", "important role in", "role in the", "in the permanent", "the permanent cell", "permanent cell cycle", "cell cycle exit", "cycle exit that", "exit that characterizes", "that characterizes senescence", "senescence narita", "narita et al.", "et al. 2003", "al. 2003 and", "2003 and 2006", "and 2006 .", "2006 . sahf", ". sahf appear", "sahf appear as", "appear as compacted", "compacted punctate", "punctate dapi stained", "dapi stained foci", "stained foci of", "foci of dna.", "of dna. each", "dna. each chromosome", "each chromosome is", "chromosome is condensed", "is condensed into", "condensed into a", "into a single", "a single sah", "single sah focus", "focus with", "with telomeric and", "telomeric and centromeric", "and centromeric chromatin", "centromeric chromatin located", "chromatin located predominantly", "located predominantly at", "predominantly at its", "at its periphery", "periphery funayama", "funayama et al.", "et al. 2006", "2006 zhang", "zhang et al.", "et al. 2007", "al. 2007 .

              an", "2007 .

              an evolutionarily", ".

              an evolutionarily conserved", "evolutionarily conserved protein", "conserved protein complex", "protein complex of", "complex of hira", "hira asf1a", "asf1a ubn1", "ubn1 and cabin1", "and cabin1 plays", "cabin1 plays a", "plays a crucial", "a crucial role", "crucial role in", "in the sahf", "the sahf formation.", "sahf formation. as", "formation. as cells", "as cells approach", "cells approach senescence", "senescence hira", "and cabin1 accumulate", "cabin1 accumulate at", "accumulate at the", "at the pml", "the pml bodies", "bodies zhang", "et al. 2005", "2005 banumathy", "banumathy et al.", "et al. 2009", "2009 rai", "rai et al.", "et al. 2011", "al. 2011 .", "2011 . pml", ". pml bodies", "pml bodies are", "bodies are punctate", "are punctate nuclear", "punctate nuclear structures", "nuclear structures that", "structures that contain", "that contain pml", "contain pml protein", "pml protein and", "protein and numerous", "and numerous other", "numerous other proteins", "other proteins and", "proteins and are", "and are proposed", "are proposed to", "proposed to be", "to be the", "be the sites", "the sites of", "sites of assembly", "of assembly of", "assembly of macromolecular", "of macromolecular regulatory", "macromolecular regulatory complexes", "regulatory complexes and", "complexes and protein", "and protein modification", "modification fogal", "fogal et al.", "et al. 2000", "2000 guo", "guo et al.", "2000 pearson", "pearson et al.", "al. 2000 .", "2000 . recruitment", ". recruitment of", "recruitment of hira", "of hira to", "hira to pml", "to pml bodies", "pml bodies coincides", "bodies coincides with", "coincides with altered", "with altered chromatin", "altered chromatin structure", "chromatin structure and", "structure and deposition", "and deposition of", "deposition of macroh2a", "of macroh2a histone", "macroh2a histone h2a", "histone h2a variant", "h2a variant onto", "variant onto chromatin.", "onto chromatin. as", "chromatin. as cells", "as cells become", "cells become senescent", "senescent hira", "and cabin1 relocate", "cabin1 relocate from", "relocate from pml", "from pml bodies", "pml bodies to", "bodies to sahf.", "to sahf. hira", "sahf. hira accumulation", "hira accumulation at", "accumulation at pml", "at pml bodies", "pml bodies is", "bodies is rb1", "tp53 independent", "independent but", "but may require", "may require phosphorylation", "require phosphorylation of", "phosphorylation of hira", "of hira serine", "hira serine s697", "serine s697 by", "s697 by gsk3b", "gsk3b ye", "ye zerlanko", "zerlanko kennedy", "kennedy et al.", "al. 2007 .", "2007 . sahf", ". sahf formation", "sahf formation itself", "itself however", "however requires", "requires functional rb1", "functional rb1 and", "rb1 and tp53", "and tp53 pathways", "pathways ye", "zerlanko zhang", "al. 2007 .

              sahf", "2007 .

              sahf contain", ".

              sahf contain h3k9me", "contain h3k9me mark", "mark characteristic", "characteristic of trancriptionally", "of trancriptionally silent", "trancriptionally silent chromatin", "chromatin and", "hp1 marcoh2a", "marcoh2a histone h2a", "h2a variant and", "variant and hmga", "and hmga proteins", "hmga proteins are", "proteins are also", "are also components", "also components of", "components of sahf", "sahf narita", "besides the hira:asf1a:ubn1:cabin1", "the hira:asf1a:ubn1:cabin1 complex.", "hira:asf1a:ubn1:cabin1 complex. a", "complex. a yet", "a yet unidentified", "yet unidentified h3k9me", "unidentified h3k9me histone", "h3k9me histone methyltransferase", "histone methyltransferase may", "methyltransferase may be", "may be recruited", "be recruited to", "recruited to sahf", "to sahf by", "sahf by ubn1", "ubn1 banumathy", "al. 2009 .", "2009 . one", ". one of", "one of the", "of the functions", "the functions of", "functions of the", "of the hira:asf1a:ubn1:cabin1", "the hira:asf1a:ubn1:cabin1 complex", "hira:asf1a:ubn1:cabin1 complex is", "complex is to", "is to deposit", "to deposit histone", "deposit histone h3.3.", "histone h3.3. variant", "h3.3. variant to", "variant to chromatin", "chromatin which", "which influences gene", "influences gene expression", "expression zhang", "2007 rai", "al. 2011 .

              further", "2011 .

              further studies", ".

              further studies are", "studies are needed", "are needed to", "needed to fully", "to fully elucidate", "fully elucidate the", "elucidate the mechanism", "the mechanism of", "mechanism of sahf", "of sahf formation", "sahf formation and", "formation and mechanism", "and mechanism by", "mechanism by which", "by which sahf", "which sahf promote", "sahf promote cell", "promote cell senescence.", "the process of dna", "process of dna damage/telomere", "of dna damage/telomere stress", "dna damage/telomere stress induced", "damage/telomere stress induced senescence", "stress induced senescence culminates", "induced senescence culminates in", "senescence culminates in the", "culminates in the formation", "in the formation of", "the formation of senescence", "foci sahf .", "sahf . these foci", ". these foci represent", "these foci represent facultative", "foci represent facultative heterochromatin", "represent facultative heterochromatin that", "facultative heterochromatin that is", "heterochromatin that is formed", "that is formed in", "is formed in senescent", "formed in senescent cells.", "in senescent cells. they", "senescent cells. they contribute", "cells. they contribute to", "they contribute to the", "contribute to the repression", "to the repression of", "the repression of proliferation", "repression of proliferation promoting", "of proliferation promoting genes", "proliferation promoting genes and", "promoting genes and play", "genes and play an", "and play an important", "play an important role", "an important role in", "important role in the", "role in the permanent", "in the permanent cell", "the permanent cell cycle", "permanent cell cycle exit", "cell cycle exit that", "cycle exit that characterizes", "exit that characterizes senescence", "characterizes senescence narita", "senescence narita et", "narita et al. 2003", "et al. 2003 and", "al. 2003 and 2006", "2003 and 2006 .", "and 2006 . sahf", "2006 . sahf appear", ". sahf appear as", "sahf appear as compacted", "as compacted punctate", "compacted punctate dapi", "punctate dapi stained foci", "dapi stained foci of", "stained foci of dna.", "foci of dna. each", "of dna. each chromosome", "dna. each chromosome is", "each chromosome is condensed", "chromosome is condensed into", "is condensed into a", "condensed into a single", "into a single sah", "a single sah focus", "sah focus with", "focus with telomeric", "with telomeric and centromeric", "telomeric and centromeric chromatin", "and centromeric chromatin located", "centromeric chromatin located predominantly", "chromatin located predominantly at", "located predominantly at its", "predominantly at its periphery", "its periphery funayama", "periphery funayama et", "funayama et al. 2006", "al. 2006 zhang", "2006 zhang et", "zhang et al. 2007", "et al. 2007 .

              an", "al. 2007 .

              an evolutionarily", "2007 .

              an evolutionarily conserved", ".

              an evolutionarily conserved protein", "evolutionarily conserved protein complex", "conserved protein complex of", "protein complex of hira", "of hira asf1a", "asf1a ubn1 and", "ubn1 and cabin1 plays", "and cabin1 plays a", "cabin1 plays a crucial", "plays a crucial role", "a crucial role in", "crucial role in the", "role in the sahf", "in the sahf formation.", "the sahf formation. as", "sahf formation. as cells", "formation. as cells approach", "as cells approach senescence", "approach senescence hira", "ubn1 and cabin1 accumulate", "and cabin1 accumulate at", "cabin1 accumulate at the", "accumulate at the pml", "at the pml bodies", "pml bodies zhang", "bodies zhang et", "zhang et al. 2005", "al. 2005 banumathy", "2005 banumathy et", "banumathy et al. 2009", "al. 2009 rai", "2009 rai et", "rai et al. 2011", "et al. 2011 .", "al. 2011 . pml", "2011 . pml bodies", ". pml bodies are", "pml bodies are punctate", "bodies are punctate nuclear", "are punctate nuclear structures", "punctate nuclear structures that", "nuclear structures that contain", "structures that contain pml", "that contain pml protein", "contain pml protein and", "pml protein and numerous", "protein and numerous other", "and numerous other proteins", "numerous other proteins and", "other proteins and are", "proteins and are proposed", "and are proposed to", "are proposed to be", "proposed to be the", "to be the sites", "be the sites of", "the sites of assembly", "sites of assembly of", "of assembly of macromolecular", "assembly of macromolecular regulatory", "of macromolecular regulatory complexes", "macromolecular regulatory complexes and", "regulatory complexes and protein", "complexes and protein modification", "protein modification fogal", "modification fogal et", "fogal et al. 2000", "al. 2000 guo", "2000 guo et", "guo et al. 2000", "al. 2000 pearson", "2000 pearson et", "pearson et al. 2000", "et al. 2000 .", "al. 2000 . recruitment", "2000 . recruitment of", ". recruitment of hira", "recruitment of hira to", "of hira to pml", "hira to pml bodies", "to pml bodies coincides", "pml bodies coincides with", "bodies coincides with altered", "coincides with altered chromatin", "with altered chromatin structure", "altered chromatin structure and", "chromatin structure and deposition", "structure and deposition of", "and deposition of macroh2a", "deposition of macroh2a histone", "of macroh2a histone h2a", "macroh2a histone h2a variant", "histone h2a variant onto", "h2a variant onto chromatin.", "variant onto chromatin. as", "onto chromatin. as cells", "chromatin. as cells become", "as cells become senescent", "become senescent hira", "ubn1 and cabin1 relocate", "and cabin1 relocate from", "cabin1 relocate from pml", "relocate from pml bodies", "from pml bodies to", "pml bodies to sahf.", "bodies to sahf. hira", "to sahf. hira accumulation", "sahf. hira accumulation at", "hira accumulation at pml", "accumulation at pml bodies", "at pml bodies is", "pml bodies is rb1", "is rb1 and", "and tp53 independent", "independent but may", "but may require phosphorylation", "may require phosphorylation of", "require phosphorylation of hira", "phosphorylation of hira serine", "of hira serine s697", "hira serine s697 by", "serine s697 by gsk3b", "by gsk3b ye", "zerlanko kennedy et", "kennedy et al. 2007", "et al. 2007 .", "al. 2007 . sahf", "2007 . sahf formation", ". sahf formation itself", "formation itself however", "however requires functional", "requires functional rb1 and", "functional rb1 and tp53", "rb1 and tp53 pathways", "tp53 pathways ye", "zerlanko zhang et", "et al. 2007 .

              sahf", "al. 2007 .

              sahf contain", "2007 .

              sahf contain h3k9me", ".

              sahf contain h3k9me mark", "h3k9me mark characteristic", "mark characteristic of", "characteristic of trancriptionally silent", "of trancriptionally silent chromatin", "silent chromatin and", "chromatin and hp1", "and hp1 marcoh2a", "hp1 marcoh2a histone", "marcoh2a histone h2a variant", "histone h2a variant and", "h2a variant and hmga", "variant and hmga proteins", "and hmga proteins are", "hmga proteins are also", "proteins are also components", "are also components of", "also components of sahf", "of sahf narita", "sahf narita et", "narita et al. 2006", "2006 besides", "besides the hira:asf1a:ubn1:cabin1 complex.", "the hira:asf1a:ubn1:cabin1 complex. a", "hira:asf1a:ubn1:cabin1 complex. a yet", "complex. a yet unidentified", "a yet unidentified h3k9me", "yet unidentified h3k9me histone", "unidentified h3k9me histone methyltransferase", "h3k9me histone methyltransferase may", "histone methyltransferase may be", "methyltransferase may be recruited", "may be recruited to", "be recruited to sahf", "recruited to sahf by", "to sahf by ubn1", "by ubn1 banumathy", "ubn1 banumathy et", "et al. 2009 .", "al. 2009 . one", "2009 . one of", ". one of the", "one of the functions", "of the functions of", "the functions of the", "functions of the hira:asf1a:ubn1:cabin1", "of the hira:asf1a:ubn1:cabin1 complex", "the hira:asf1a:ubn1:cabin1 complex is", "hira:asf1a:ubn1:cabin1 complex is to", "complex is to deposit", "is to deposit histone", "to deposit histone h3.3.", "deposit histone h3.3. variant", "histone h3.3. variant to", "h3.3. variant to chromatin", "to chromatin which", "chromatin which influences", "which influences gene expression", "gene expression zhang", "expression zhang et", "al. 2007 rai", "2007 rai et", "et al. 2011 .

              further", "al. 2011 .

              further studies", "2011 .

              further studies are", ".

              further studies are needed", "studies are needed to", "are needed to fully", "needed to fully elucidate", "to fully elucidate the", "fully elucidate the mechanism", "elucidate the mechanism of", "the mechanism of sahf", "mechanism of sahf formation", "of sahf formation and", "sahf formation and mechanism", "formation and mechanism by", "and mechanism by which", "mechanism by which sahf", "by which sahf promote", "which sahf promote cell", "sahf promote cell senescence.", "the process of dna damage/telomere", "process of dna damage/telomere stress", "of dna damage/telomere stress induced", "dna damage/telomere stress induced senescence", "damage/telomere stress induced senescence culminates", "stress induced senescence culminates in", "induced senescence culminates in the", "senescence culminates in the formation", "culminates in the formation of", "in the formation of senescence", "the formation of senescence associated", "heterochromatin foci sahf .", "foci sahf . these", "sahf . these foci represent", ". these foci represent facultative", "these foci represent facultative heterochromatin", "foci represent facultative heterochromatin that", "represent facultative heterochromatin that is", "facultative heterochromatin that is formed", "heterochromatin that is formed in", "that is formed in senescent", "is formed in senescent cells.", "formed in senescent cells. they", "in senescent cells. they contribute", "senescent cells. they contribute to", "cells. they contribute to the", "they contribute to the repression", "contribute to the repression of", "to the repression of proliferation", "the repression of proliferation promoting", "repression of proliferation promoting genes", "of proliferation promoting genes and", "proliferation promoting genes and play", "promoting genes and play an", "genes and play an important", "and play an important role", "play an important role in", "an important role in the", "important role in the permanent", "role in the permanent cell", "in the permanent cell cycle", "the permanent cell cycle exit", "permanent cell cycle exit that", "cell cycle exit that characterizes", "cycle exit that characterizes senescence", "that characterizes senescence narita", "characterizes senescence narita et", "senescence narita et al.", "narita et al. 2003 and", "et al. 2003 and 2006", "al. 2003 and 2006 .", "2003 and 2006 . sahf", "and 2006 . sahf appear", "2006 . sahf appear as", ". sahf appear as compacted", "appear as compacted punctate", "as compacted punctate dapi", "compacted punctate dapi stained", "punctate dapi stained foci of", "dapi stained foci of dna.", "stained foci of dna. each", "foci of dna. each chromosome", "of dna. each chromosome is", "dna. each chromosome is condensed", "each chromosome is condensed into", "chromosome is condensed into a", "is condensed into a single", "condensed into a single sah", "into a single sah focus", "single sah focus with", "sah focus with telomeric", "focus with telomeric and", "with telomeric and centromeric chromatin", "telomeric and centromeric chromatin located", "and centromeric chromatin located predominantly", "centromeric chromatin located predominantly at", "chromatin located predominantly at its", "located predominantly at its periphery", "at its periphery funayama", "its periphery funayama et", "periphery funayama et al.", "et al. 2006 zhang", "al. 2006 zhang et", "2006 zhang et al.", "zhang et al. 2007 .

              an", "et al. 2007 .

              an evolutionarily", "al. 2007 .

              an evolutionarily conserved", "2007 .

              an evolutionarily conserved protein", ".

              an evolutionarily conserved protein complex", "evolutionarily conserved protein complex of", "conserved protein complex of hira", "complex of hira asf1a", "hira asf1a ubn1", "asf1a ubn1 and cabin1", "ubn1 and cabin1 plays a", "and cabin1 plays a crucial", "cabin1 plays a crucial role", "plays a crucial role in", "a crucial role in the", "crucial role in the sahf", "role in the sahf formation.", "in the sahf formation. as", "the sahf formation. as cells", "sahf formation. as cells approach", "formation. as cells approach senescence", "cells approach senescence hira", "senescence hira asf1a", "ubn1 and cabin1 accumulate at", "and cabin1 accumulate at the", "cabin1 accumulate at the pml", "accumulate at the pml bodies", "the pml bodies zhang", "pml bodies zhang et", "bodies zhang et al.", "et al. 2005 banumathy", "al. 2005 banumathy et", "2005 banumathy et al.", "et al. 2009 rai", "al. 2009 rai et", "2009 rai et al.", "rai et al. 2011 .", "et al. 2011 . pml", "al. 2011 . pml bodies", "2011 . pml bodies are", ". pml bodies are punctate", "pml bodies are punctate nuclear", "bodies are punctate nuclear structures", "are punctate nuclear structures that", "punctate nuclear structures that contain", "nuclear structures that contain pml", "structures that contain pml protein", "that contain pml protein and", "contain pml protein and numerous", "pml protein and numerous other", "protein and numerous other proteins", "and numerous other proteins and", "numerous other proteins and are", "other proteins and are proposed", "proteins and are proposed to", "and are proposed to be", "are proposed to be the", "proposed to be the sites", "to be the sites of", "be the sites of assembly", "the sites of assembly of", "sites of assembly of macromolecular", "of assembly of macromolecular regulatory", "assembly of macromolecular regulatory complexes", "of macromolecular regulatory complexes and", "macromolecular regulatory complexes and protein", "regulatory complexes and protein modification", "and protein modification fogal", "protein modification fogal et", "modification fogal et al.", "et al. 2000 guo", "al. 2000 guo et", "2000 guo et al.", "et al. 2000 pearson", "al. 2000 pearson et", "2000 pearson et al.", "pearson et al. 2000 .", "et al. 2000 . recruitment", "al. 2000 . recruitment of", "2000 . recruitment of hira", ". recruitment of hira to", "recruitment of hira to pml", "of hira to pml bodies", "hira to pml bodies coincides", "to pml bodies coincides with", "pml bodies coincides with altered", "bodies coincides with altered chromatin", "coincides with altered chromatin structure", "with altered chromatin structure and", "altered chromatin structure and deposition", "chromatin structure and deposition of", "structure and deposition of macroh2a", "and deposition of macroh2a histone", "deposition of macroh2a histone h2a", "of macroh2a histone h2a variant", "macroh2a histone h2a variant onto", "histone h2a variant onto chromatin.", "h2a variant onto chromatin. as", "variant onto chromatin. as cells", "onto chromatin. as cells become", "chromatin. as cells become senescent", "cells become senescent hira", "senescent hira asf1a", "ubn1 and cabin1 relocate from", "and cabin1 relocate from pml", "cabin1 relocate from pml bodies", "relocate from pml bodies to", "from pml bodies to sahf.", "pml bodies to sahf. hira", "bodies to sahf. hira accumulation", "to sahf. hira accumulation at", "sahf. hira accumulation at pml", "hira accumulation at pml bodies", "accumulation at pml bodies is", "at pml bodies is rb1", "bodies is rb1 and", "is rb1 and tp53", "tp53 independent but", "independent but may require", "but may require phosphorylation of", "may require phosphorylation of hira", "require phosphorylation of hira serine", "phosphorylation of hira serine s697", "of hira serine s697 by", "hira serine s697 by gsk3b", "s697 by gsk3b ye", "gsk3b ye zerlanko", "ye zerlanko kennedy", "zerlanko kennedy et al.", "kennedy et al. 2007 .", "et al. 2007 . sahf", "al. 2007 . sahf formation", "2007 . sahf formation itself", "sahf formation itself however", "itself however requires", "however requires functional rb1", "requires functional rb1 and tp53", "functional rb1 and tp53 pathways", "and tp53 pathways ye", "pathways ye zerlanko", "ye zerlanko zhang", "zerlanko zhang et al.", "zhang et al. 2007 .

              sahf", "et al. 2007 .

              sahf contain", "al. 2007 .

              sahf contain h3k9me", "2007 .

              sahf contain h3k9me mark", "contain h3k9me mark characteristic", "h3k9me mark characteristic of", "mark characteristic of trancriptionally", "characteristic of trancriptionally silent chromatin", "trancriptionally silent chromatin and", "silent chromatin and hp1", "and hp1 marcoh2a histone", "hp1 marcoh2a histone h2a", "marcoh2a histone h2a variant and", "histone h2a variant and hmga", "h2a variant and hmga proteins", "variant and hmga proteins are", "and hmga proteins are also", "hmga proteins are also components", "proteins are also components of", "are also components of sahf", "components of sahf narita", "of sahf narita et", "sahf narita et al.", "al. 2006 besides", "2006 besides the", "besides the hira:asf1a:ubn1:cabin1 complex. a", "the hira:asf1a:ubn1:cabin1 complex. a yet", "hira:asf1a:ubn1:cabin1 complex. a yet unidentified", "complex. a yet unidentified h3k9me", "a yet unidentified h3k9me histone", "yet unidentified h3k9me histone methyltransferase", "unidentified h3k9me histone methyltransferase may", "h3k9me histone methyltransferase may be", "histone methyltransferase may be recruited", "methyltransferase may be recruited to", "may be recruited to sahf", "be recruited to sahf by", "recruited to sahf by ubn1", "sahf by ubn1 banumathy", "by ubn1 banumathy et", "ubn1 banumathy et al.", "banumathy et al. 2009 .", "et al. 2009 . one", "al. 2009 . one of", "2009 . one of the", ". one of the functions", "one of the functions of", "of the functions of the", "the functions of the hira:asf1a:ubn1:cabin1", "functions of the hira:asf1a:ubn1:cabin1 complex", "of the hira:asf1a:ubn1:cabin1 complex is", "the hira:asf1a:ubn1:cabin1 complex is to", "hira:asf1a:ubn1:cabin1 complex is to deposit", "complex is to deposit histone", "is to deposit histone h3.3.", "to deposit histone h3.3. variant", "deposit histone h3.3. variant to", "histone h3.3. variant to chromatin", "variant to chromatin which", "to chromatin which influences", "chromatin which influences gene", "influences gene expression zhang", "gene expression zhang et", "expression zhang et al.", "et al. 2007 rai", "al. 2007 rai et", "2007 rai et al.", "rai et al. 2011 .

              further", "et al. 2011 .

              further studies", "al. 2011 .

              further studies are", "2011 .

              further studies are needed", ".

              further studies are needed to", "studies are needed to fully", "are needed to fully elucidate", "needed to fully elucidate the", "to fully elucidate the mechanism", "fully elucidate the mechanism of", "elucidate the mechanism of sahf", "the mechanism of sahf formation", "mechanism of sahf formation and", "of sahf formation and mechanism", "sahf formation and mechanism by", "formation and mechanism by which", "and mechanism by which sahf", "mechanism by which sahf promote", "by which sahf promote cell", "which sahf promote cell senescence." ] }, { "record_id": "GLY_000594_1_1336", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3000484", "r hsa", "hsa 3000484", "r hsa 3000484" ] }, { "record_id": "GLY_000594_1_1336", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "scavenging by", "by class", "class f", "f receptors", "scavenging by class", "by class f", "class f receptors", "scavenging by class f", "by class f receptors", "scavenging by class f receptors", "srec i", "and scarf2", "srec ii", "are transmembrane", "transmembrane proteins", "proteins that", "that contain", "contain multiple", "multiple extracellular", "extracellular egf", "egf like", "like domains", "ishii et", "et al.", "al. 2002", "reviewed in", "in areschoug", "areschoug and", "and gordon", "gordon 2009", "2009 .", ". scarf2", "scarf2 may", "may be", "be involved", "involved in", "in cell", "cell adhesion", "adhesion rather", "rather than", "than ligand", "ligand binding.", "scarf1 srec", "i and", "scarf2 srec", "ii are", "are transmembrane proteins", "transmembrane proteins that", "proteins that contain", "that contain multiple", "contain multiple extracellular", "multiple extracellular egf", "extracellular egf like", "egf like domains", "domains ishii", "ishii et al.", "et al. 2002", "2002 reviewed", "reviewed in areschoug", "in areschoug and", "areschoug and gordon", "and gordon 2009", "gordon 2009 .", "2009 . scarf2", ". scarf2 may", "scarf2 may be", "may be involved", "be involved in", "involved in cell", "in cell adhesion", "cell adhesion rather", "adhesion rather than", "rather than ligand", "than ligand binding.", "scarf1 srec i", "srec i and", "i and scarf2", "and scarf2 srec", "scarf2 srec ii", "srec ii are", "ii are transmembrane", "are transmembrane proteins that", "transmembrane proteins that contain", "proteins that contain multiple", "that contain multiple extracellular", "contain multiple extracellular egf", "multiple extracellular egf like", "extracellular egf like domains", "like domains ishii", "domains ishii et", "ishii et al. 2002", "al. 2002 reviewed", "2002 reviewed in", "reviewed in areschoug and", "in areschoug and gordon", "areschoug and gordon 2009", "and gordon 2009 .", "gordon 2009 . scarf2", "2009 . scarf2 may", ". scarf2 may be", "scarf2 may be involved", "may be involved in", "be involved in cell", "involved in cell adhesion", "in cell adhesion rather", "cell adhesion rather than", "adhesion rather than ligand", "rather than ligand binding.", "srec i and scarf2", "and scarf2 srec ii", "srec ii are transmembrane", "ii are transmembrane proteins", "are transmembrane proteins that contain", "transmembrane proteins that contain multiple", "proteins that contain multiple extracellular", "that contain multiple extracellular egf", "contain multiple extracellular egf like", "multiple extracellular egf like domains", "egf like domains ishii", "like domains ishii et", "domains ishii et al.", "et al. 2002 reviewed", "al. 2002 reviewed in", "2002 reviewed in areschoug", "reviewed in areschoug and gordon", "in areschoug and gordon 2009", "areschoug and gordon 2009 .", "and gordon 2009 . scarf2", "gordon 2009 . scarf2 may", "2009 . scarf2 may be", ". scarf2 may be involved", "scarf2 may be involved in", "may be involved in cell", "be involved in cell adhesion", "involved in cell adhesion rather", "in cell adhesion rather than", "cell adhesion rather than ligand", "adhesion rather than ligand binding." ] }, { "record_id": "GLY_000594_1_1337", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3000497", "r hsa", "hsa 3000497", "r hsa 3000497" ] }, { "record_id": "GLY_000594_1_1337", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "scavenging by", "by class", "class h", "h receptors", "scavenging by class", "by class h", "class h receptors", "scavenging by class h", "by class h receptors", "scavenging by class h receptors", "feel 1", "and stab2", "feel 2", "are very", "very large", "large transmambrane", "transmambrane proteins", "proteins containing", "containing fasciclin", "fasciclin domains", "egf like", "like domains", "and hyaluronan", "hyaluronan like", "politz et", "et al.", "al. 2002", "reviewed in", "in areschoug", "areschoug and", "and gordon", "gordon 2009", "2009 .", "stab1 feel", "1 and", "stab2 feel", "2 are", "are very large", "very large transmambrane", "large transmambrane proteins", "transmambrane proteins containing", "proteins containing fasciclin", "containing fasciclin domains", "domains egf", "egf like domains", "domains and", "and hyaluronan like", "hyaluronan like domains", "domains politz", "politz et al.", "et al. 2002", "2002 reviewed", "reviewed in areschoug", "in areschoug and", "areschoug and gordon", "and gordon 2009", "gordon 2009 .", "stab1 feel 1", "feel 1 and", "1 and stab2", "and stab2 feel", "stab2 feel 2", "feel 2 are", "2 are very", "are very large transmambrane", "very large transmambrane proteins", "large transmambrane proteins containing", "transmambrane proteins containing fasciclin", "proteins containing fasciclin domains", "fasciclin domains egf", "domains egf like", "like domains and", "domains and hyaluronan", "and hyaluronan like domains", "like domains politz", "domains politz et", "politz et al. 2002", "al. 2002 reviewed", "2002 reviewed in", "reviewed in areschoug and", "in areschoug and gordon", "areschoug and gordon 2009", "and gordon 2009 .", "feel 1 and stab2", "and stab2 feel 2", "feel 2 are very", "2 are very large", "are very large transmambrane proteins", "very large transmambrane proteins containing", "large transmambrane proteins containing fasciclin", "transmambrane proteins containing fasciclin domains", "containing fasciclin domains egf", "fasciclin domains egf like", "domains egf like domains", "egf like domains and", "like domains and hyaluronan", "domains and hyaluronan like", "hyaluronan like domains politz", "like domains politz et", "domains politz et al.", "et al. 2002 reviewed", "al. 2002 reviewed in", "2002 reviewed in areschoug", "reviewed in areschoug and gordon", "in areschoug and gordon 2009", "areschoug and gordon 2009 ." ] }, { "record_id": "GLY_000594_1_1338", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3134963", "r hsa", "hsa 3134963", "r hsa 3134963" ] }, { "record_id": "GLY_000594_1_1338", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dex/h box", "box helicases", "helicases activate", "activate type", "type i", "i ifn", "ifn and", "and inflammatory", "inflammatory cytokines", "cytokines production", "dex/h box helicases", "box helicases activate", "helicases activate type", "activate type i", "type i ifn", "i ifn and", "ifn and inflammatory", "and inflammatory cytokines", "inflammatory cytokines production", "dex/h box helicases activate", "box helicases activate type", "helicases activate type i", "activate type i ifn", "type i ifn and", "i ifn and inflammatory", "ifn and inflammatory cytokines", "and inflammatory cytokines production", "dex/h box helicases activate type", "box helicases activate type i", "helicases activate type i ifn", "activate type i ifn and", "type i ifn and inflammatory", "i ifn and inflammatory cytokines", "ifn and inflammatory cytokines production", "dhx36 and", "and dhx9", "dhx9 are", "are aspartate", "aspartate glutamate", "glutamate any", "any amino", "amino acid", "acid aspartate/histidine", "box helicase", "proteins that", "that localize", "localize in", "in the", "the cytosol.", "cytosol. the", "the dhx", "dhx rna", "rna helicases", "helicases family", "family includes", "includes a", "a large", "large number", "number of", "of proteins", "that are", "are implicated", "implicated in", "in rna", "rna metabolism.", "metabolism. members", "members of", "of this", "this family", "rig 1", "1 and", "and mda5", "have been", "been shown", "shown to", "to sense", "sense a", "a non", "non self", "self rna", "rna leading", "leading to", "to type", "ifn production.", "production. rna", "helicases dhx36", "dhx9 were", "were found", "found to", "to trigger", "trigger host", "host responses", "responses to", "to non", "self dna", "dna in", "in myd88", "myd88 dependent", "dependent manner.", "manner. dhx36", "dhx36 sensed", "sensed cpg", "cpg 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"both dhx36 and", "dhx9 were critical", "were critical for", "critical for antiviral", "for antiviral immune", "antiviral immune responses", "immune responses in", "responses in viral", "in viral dna", "viral dna stimulated", "dna stimulated human", "stimulated human plasmacytoid", "human plasmacytoid dendritic", "plasmacytoid dendritic cells", "cells pdc", "kim t et", "t et al.", "et al. 2010", "al. 2010 .", "dhx36 and dhx9 are", "and dhx9 are aspartate", "dhx9 are aspartate glutamate", "are aspartate glutamate any", "aspartate glutamate any amino", "glutamate any amino acid", "any amino acid aspartate/histidine", "acid aspartate/histidine dexd/h", "dexd/h box helicase", "box helicase dhx", "dhx proteins that", "proteins that localize in", "that localize in the", "localize in the cytosol.", "in the cytosol. the", "the cytosol. the dhx", "cytosol. the dhx rna", "the dhx rna helicases", "dhx rna helicases family", "rna helicases family includes", "helicases family includes a", "family 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biotin therapy. most patients", "biotin therapy. most patients respond", "therapy. most patients respond favourably", "most patients respond favourably to", "patients respond favourably to treatment", "respond favourably to treatment and", "favourably to treatment and show", "to treatment and show complete", "treatment and show complete reversal", "and show complete reversal of", "show complete reversal of biochemical", "complete reversal of biochemical and", "reversal of biochemical and clinical", "of biochemical and clinical symptoms", "and clinical symptoms morrone", "clinical symptoms morrone et", "symptoms morrone et al.", "et al. 2002 dupuis", "al. 2002 dupuis et", "2002 dupuis et al.", "dupuis et al. 1999 .", "et al. 1999 . here", "al. 1999 . here mutations", "1999 . here mutations in", ". here mutations in the", "here mutations in the hlcs", "mutations in the hlcs active", "in the hlcs active site", "the hlcs active site cause", "hlcs active site cause a", "active site cause a reduced", "site cause a reduced affinity", "cause a reduced affinity for", "a reduced affinity for biotin", "reduced affinity for biotin that", "affinity for biotin that can", "for biotin that can be", "biotin that can be overcome", "that can be overcome by", "can be overcome by pharmacological", "be overcome by pharmacological doses", "overcome by pharmacological doses of", "by pharmacological doses of the", "pharmacological doses of the vitamin", "of the vitamin pendini", "the vitamin pendini et", "vitamin pendini et al.", "pendini et al. 2008 .", "et al. 2008 . patients", "al. 2008 . patients who", "2008 . patients who display", ". patients who display incomplete", "patients who display incomplete responsiveness", "who display incomplete responsiveness to", "display incomplete responsiveness to biotin", "incomplete responsiveness to biotin therapy", "responsiveness to biotin therapy have", "to biotin therapy have a", "biotin therapy have a poor", "therapy have a poor long", "have a poor long term", "a poor long term prognosis", "long term prognosis bailey", "term prognosis bailey et", "prognosis bailey et al.", "bailey et al. 2008 .", "al. 2008 . here", "2008 . here mutations", ". here mutations that", "here mutations that reside outside", "mutations that reside outside of", "that reside outside of the", "reside outside of the enzyme's", "outside of the enzyme's active", "of the enzyme's active site", "the enzyme's active site have", "enzyme's active site have no", "active site have no effect", "site have no effect on", "have no effect on biotin", "no effect on biotin binding", "effect on biotin binding but", "on biotin binding but do", "biotin binding but do compromise", "binding but do compromise the", "but do compromise the protein", "do compromise the protein protein", "compromise the protein protein interaction", "the protein protein interaction between", "protein protein interaction between the", "protein interaction between the hlcs", "interaction between the hlcs and", "between the hlcs and its", "the hlcs and its substrates", "and its substrates resulting", "its substrates resulting in", "substrates resulting in reduced", "resulting in reduced biotinylation of", "in reduced biotinylation of all", "reduced biotinylation of all five", "biotinylation of all five carboxylases", "of all five carboxylases thus", "all five carboxylases thus reducing", "five carboxylases thus reducing their", "carboxylases thus reducing their enzymatic", "thus reducing their enzymatic activity", "their enzymatic activity mayende", "enzymatic activity mayende et", "activity mayende et al.", "mayende et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1347", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "351200", "r hsa", "hsa 351200", "r hsa 351200" ] }, { "record_id": "GLY_000594_1_1347", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interconversion of", "of polyamines", "interconversion of polyamines", "the reactions", "reactions catalyzed", "catalyzed by", "by aminopropyl", "aminopropyl transferases", "transferases annotated", "annotated above", "above are", "are generally", "generally irreversible.", "irreversible. but", "but spermine", "spermine and", "and spermidine", "spermidine can", "can be", "be recycled", "recycled respectively", "respectively into", "into spermidine", "spermidine and", "and putrescine.", "putrescine. these", "these events", "events require", "require the", "the formation", "formation of", "of n", "n acetylated", "acetylated intermediates", "n1 acetylspermine", "acetylspermine and", "and n1", "n1 acetylspermidine", "acetylspermidine catalyzed", "by a", "a cytosolic", "cytosolic acetyl", "acetyl coa:spermidine/spermine", "coa:spermidine/spermine n1", "n1 acetyl", "acetyl tranferase", "polyamine oxidase", "a fad", "fad enzyme", "enzyme present", "present in", "in the", "the peroxysomes", "yields a", "a polyamine", "polyamine with", "with release", "release of", "of an", "an aldehyde", "3 acetamindopropanal", "and h2o2.
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              subsequently", "enzyme.
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              in", "h2o2.
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              subsequently", "ssat enzyme.
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              in", "acetamindopropanal and h2o2.
              in addition", "and h2o2.
              in addition smox", "addition smox a", "smox a fad dependent", "a fad dependent polyamine", "fad dependent polyamine oxidase", "oxidase paoh1/smo that", "paoh1/smo that can efficiently", "that can efficiently use spermine", "can efficiently use spermine as", "efficiently use spermine as a", "use spermine as a substrate", "spermine as a substrate and", "as a substrate and is", "a substrate and is involved", "substrate and is involved in", "and is involved in interconversion", "is involved in interconversion reactions." ] }, { "record_id": "GLY_000594_1_1348", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "351202", "r hsa", "hsa 351202", "r hsa 351202" ] }, { "record_id": "GLY_000594_1_1348", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "metabolism of", "of polyamines", "metabolism of polyamines", "polyamines is", "is a", "a family", "family of", "of molecules", "i.e. putrescine", 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abnormalities", "multiple abnormalities in", "abnormalities in the", "in the control", "the control of", "control of polyamines", "of polyamines metabolism", "polyamines metabolism might", "metabolism might be", "might be implicated", "be implicated in", "implicated in several", "in several pathological", "several pathological processes", "processes moinard", "moinard et al.", "al. 2005", ". legend", "legend for the", "for the following", "the following figure:", "polyamines is a family", "is a family of", "a family of molecules", "of molecules i.e.", "molecules i.e. putrescine", "i.e. putrescine spermine", "spermidine derived from", "derived from ornithine according", "from ornithine according to", "ornithine according to a", "according to a decarboxylation/condensative", "to a decarboxylation/condensative process.", "a decarboxylation/condensative process. more", "decarboxylation/condensative process. more recently", "more recently it", "recently it has", "it has been demonstrated", 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"metabolism and the fact", "and the fact that", "the fact that polyamines", "fact that polyamines homeostasis", "that polyamines homeostasis is", "polyamines homeostasis is tightly", "homeostasis is tightly regulated", "is tightly regulated support", "tightly regulated support the", "regulated support the idea", "support the idea that", "the idea that polyamines", "idea that polyamines are", "that polyamines are essential", "polyamines are essential to", "are essential to cell", "essential to cell survival.", "to cell survival. multiple", "cell survival. multiple abnormalities", "survival. multiple abnormalities in", "multiple abnormalities in the", "abnormalities in the control", "in the control of", "the control of polyamines", "control of polyamines metabolism", "of polyamines metabolism might", "polyamines metabolism might be", "metabolism might be implicated", "might be implicated in", "be implicated in several", "implicated in several pathological", "in several pathological processes", "pathological processes moinard", "processes moinard et", "et al. 2005", "al. 2005 .", "2005 . legend", ". legend for", "legend for the following", "for the following figure:", "polyamines is a family of", "is a family of molecules", "family of molecules i.e.", "of molecules i.e. putrescine", "putrescine spermine spermidine", "spermine spermidine derived", "spermidine derived from ornithine", "derived from ornithine according to", "from ornithine according to a", "ornithine according to a decarboxylation/condensative", "according to a decarboxylation/condensative process.", "to a decarboxylation/condensative process. more", "a decarboxylation/condensative process. more recently", "process. more recently it", "more recently it has", "recently it has been", "it has been demonstrated that", "has been demonstrated that arginine", "been demonstrated that arginine can", "demonstrated that arginine can be", "that arginine can be metabolised", "arginine can be metabolised 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"their metabolism and the fact", "metabolism and the fact that", "and the fact that polyamines", "the fact that polyamines homeostasis", "fact that polyamines homeostasis is", "that polyamines homeostasis is tightly", "polyamines homeostasis is tightly regulated", "homeostasis is tightly regulated support", "is tightly regulated support the", "tightly regulated support the idea", "regulated support the idea that", "support the idea that polyamines", "the idea that polyamines are", "idea that polyamines are essential", "that polyamines are essential to", "polyamines are essential to cell", "are essential to cell survival.", "essential to cell survival. multiple", "to cell survival. multiple abnormalities", "cell survival. multiple abnormalities in", "survival. multiple abnormalities in the", "multiple abnormalities in the control", "abnormalities in the control of", "in the control of polyamines", "the control of polyamines metabolism", "control of polyamines metabolism might", "of 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adhesion proteins", "apoptotic cleavage of cell adhesion", "of cell adhesion proteins", "apoptotic cells", "show dramatic", "dramatic rearrangements", "rearrangements of", "of tight", "tight junctions", "adherens junctions", "and desmosomes", "abreu et", "et al.", "2000 .", ". desmosome", "desmosome specific", "specific members", "members of", "of the", "the cadherin", "cadherin superfamily", "superfamily of", "adhesion molecules", "molecules including", "desmoglein 3", "plakophilin 1", "and desmoplakin", "desmoplakin are", "cleaved by", "by caspases", "caspases after", "after onset", "onset of", "of apoptosis", "weiske et", "2001 .", "cleavage results", "results in", "in the", "the disruption", "disruption of", "the desmosome", "desmosome structure", "structure and", "and thus", "thus contributes", "contributes to", "to cell", "cell rounding", "rounding and", "and disintegration", "disintegration of", "the intermediate", "intermediate filament", "filament system", "cells show", "show 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classical tay sachs disease", "classical tay sachs disease is", "tay sachs disease is characterised", "sachs disease is characterised by", "disease is characterised by infant", "is characterised by infant onset", "characterised by infant onset neurodegeneration", "by infant onset neurodegeneration followed", "infant onset neurodegeneration followed by", "onset neurodegeneration followed by paralysis", "followed by paralysis dementia", "by paralysis dementia and", "paralysis dementia and blindness", "dementia and blindness death", "and blindness death occurs", "blindness death occurs by", "death occurs by the age", "occurs by the age of", "by the age of 2", "the age of 2 or", "age of 2 or 3", "2 or 3 okada", "or 3 okada et", "3 okada et al.", "okada et al. 1971 .", "et al. 1971 . the", "al. 1971 . the two", "1971 . the two other", ". the two other forms", "the two other forms of", "two other forms of tay", "other forms of tay sachs", "forms of tay sachs disease", "tay sachs disease 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              defects", "cells.

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              defects", "in neuronal cells.

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exercise", "with exercise intolerance", "exercise intolerance and", "intolerance and cardiomyopathy", "cardiomyopathy kolberg", "kolberg et al.", "et al. 2007", "2007 cameron", "cameron et al.", "et al. 2009", "al. 2009 .", "synthase 1 gys1", "1 gys1 \\muscle\\", "gys1 \\muscle\\ is", "\\muscle\\ is widely", "is widely expressed in", "widely expressed in the", "expressed in the body.", "in the body. it", "the body. it normally", "body. it normally catalyzes", "it normally catalyzes the", "normally catalyzes the addition", "catalyzes the addition of", "the addition of glucose", "addition of glucose residues", "of glucose residues to", "glucose residues to a", "residues to a growing", "to a growing glycogen", "a growing glycogen molecule.", "growing glycogen molecule. in", "glycogen molecule. in its", "molecule. in its absence", "its absence glycogen", "absence glycogen synthesis", "glycogen synthesis fails. this", "synthesis fails. this deficiency", "fails. this deficiency is", "this deficiency is most", "deficiency is most prominently", "is most prominently associated", "most prominently associated with", "prominently associated with exercise", "associated with exercise intolerance", "with exercise intolerance and", "exercise intolerance and cardiomyopathy", "and cardiomyopathy kolberg", "cardiomyopathy kolberg et", "kolberg et al. 2007", "al. 2007 cameron", "2007 cameron et", "cameron et al. 2009", "et al. 2009 .", "glycogen synthase 1 gys1", "synthase 1 gys1 \\muscle\\", "gys1 \\muscle\\ is widely", "\\muscle\\ is widely expressed", "is widely expressed in the", "widely expressed in the body.", "expressed in the body. it", "in the body. it normally", "the body. it normally catalyzes", "body. it normally catalyzes the", "it normally catalyzes the addition", "normally catalyzes the addition of", "catalyzes the addition of glucose", "the addition of glucose residues", "addition of glucose residues to", "of glucose residues to a", "glucose residues to a growing", 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              due", "own tissues.
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              due to its ability", "to its ability to", "its ability to modulate", "ability to modulate immune", "to modulate immune responses", "immune responses ctla", "responses ctla 4", "ctla 4 has emerged", "4 has emerged as", "has emerged as a", "emerged as a significant", "as a significant therapeutic", "a significant therapeutic target", "significant therapeutic target for", "therapeutic target for managing", "target for managing conditions", "for managing conditions such", "managing conditions such as", "conditions such as cancer", "as cancer autoimmune", "cancer autoimmune diseases", "autoimmune diseases and", "diseases and transplant", "transplant rejection tivol", "rejection tivol et", "tivol et al. 1995", "al. 1995 chambers", "1995 chambers et", "chambers et al. 1997", "al. 1997 rudd", "1997 rudd and", "rudd and schneider 2003", "and schneider 2003 .", "cytotoxic t lymphocyte antigen 4", "lymphocyte antigen 4 ctla", "antigen 4 ctla 4", "ctla 4 is an", "4 is an immune", "is an immune checkpoint molecule", "an immune checkpoint molecule predominantly", "immune checkpoint molecule predominantly expressed", "checkpoint molecule predominantly expressed on", "molecule predominantly expressed on the", "predominantly expressed on the surface", "expressed on the surface of", "on the surface of activated", "the surface of activated t", "surface of activated t cells", "of activated t cells and", "activated t cells and regulatory", "t cells and regulatory t", "and regulatory t treg", "t treg cells.", "treg cells. it plays", "cells. it plays a critical", "it plays a critical role", "plays a critical role in", "a critical role in inhibiting", "critical role in inhibiting t", "role in inhibiting t cell", "in inhibiting t cell activation", "inhibiting t cell activation and", "t cell activation and maintaining", "cell activation and maintaining immune", "activation and maintaining immune homeostasis", "maintaining immune homeostasis alegre", "immune homeostasis alegre et", "homeostasis alegre et al.", "alegre et al. 2001 .", "et al. 2001 . after", "al. 2001 . after acctivation", "2001 . after acctivation of", ". after acctivation of t", "after acctivation of t lymphocytes", "acctivation of t lymphocytes through", "of t lymphocytes through their", "t lymphocytes through their antigen", "lymphocytes through their antigen receptor", "their antigen receptor tcr", "receptor tcr induces", "tcr induces the upregulation", "induces the upregulation of ctla", "the upregulation of ctla 4", "upregulation of ctla 4 expression.", "of ctla 4 expression. ctla", "ctla 4 expression. ctla 4", "4 expression. ctla 4 engagement", "expression. ctla 4 engagement alongside", "ctla 4 engagement alongside tcr", "4 engagement alongside tcr activation", "engagement alongside tcr activation inhibits", "alongside tcr activation inhibits t", "tcr activation inhibits t cell", "activation inhibits t cell responses", "inhibits t cell responses through", "t cell responses through two", "cell responses through two primary", "responses through two primary mechanisms:", "through two primary mechanisms: competing", "two primary mechanisms: competing with", "primary mechanisms: competing with cd28", "mechanisms: competing with cd28 for", "competing with cd28 for b7", "with cd28 for b7 binding", "cd28 for b7 binding to", "for b7 binding to reduce", "b7 binding to reduce costimulation", "to reduce costimulation and", "reduce costimulation and delivering", "costimulation and delivering a", "and delivering a negative signal", "delivering a negative signal directly", "a negative signal directly into", "negative signal directly into the", "signal directly into the t", "directly into the t cells.", "into the t cells. it", "the t cells. it has", "t cells. it has been", "cells. it has been reported", "it has been reported that", "has been reported that phosphotyrosine", "been reported that phosphotyrosine dependent", "reported that phosphotyrosine dependent recruitment", "that phosphotyrosine dependent recruitment of", "phosphotyrosine dependent recruitment of the", "dependent recruitment of the shp", "recruitment of the shp 2", "of the shp 2 phosphatase", "the shp 2 phosphatase to", "shp 2 phosphatase to ctla", "2 phosphatase to ctla 4", "phosphatase to ctla 4 inhibits", "to ctla 4 inhibits t", "ctla 4 inhibits t cell", "4 inhibits t cell activation", "inhibits t cell activation and", "t cell activation and expansion", "cell activation and expansion by", "activation and expansion by dephosphorylation", "and expansion by dephosphorylation of", "expansion by dephosphorylation of cd3/tcr", "by dephosphorylation of cd3/tcr chains.", "dephosphorylation of cd3/tcr chains.
              ctla", "of cd3/tcr chains.
              ctla 4", "cd3/tcr chains.
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co2 is in equilibrium", "co2 is in equilibrium with", "is in equilibrium with bicarbonate", "equilibrium with bicarbonate hco3", "hco3 and is", "and is the body's central", "is the body's central ph", "the body's central ph buffering", "body's central ph buffering system.", "central ph buffering system. hco3", "buffering system. hco3 is", "system. hco3 is charged", "hco3 is charged so", "is charged so cannot move", "charged so cannot move across", "so cannot move across membranes", "cannot move across membranes unaided.", "move across membranes unaided. the", "across membranes unaided. the bicarbonate", "membranes unaided. the bicarbonate transport", "unaided. the bicarbonate transport proteins", "the bicarbonate transport proteins move", "bicarbonate transport proteins move bicarbonate", "transport proteins move bicarbonate across", "proteins move bicarbonate across the", "move bicarbonate across the membrane.", "bicarbonate across the membrane. there", "across the membrane. there are", "the membrane. there are 14", "membrane. there are 14 genes", "there are 14 genes which", "are 14 genes which encode", "14 genes which encode these", "genes which encode these transport", "which encode these transport proteins", "encode these transport proteins in", "these transport proteins in mammals.", "transport proteins in mammals. applying", "proteins in mammals. applying the", "in mammals. applying the human", "mammals. applying the human genome", "applying the human genome organization's", "the human genome organization's sytematic", "human genome organization's sytematic nomenclature", "genome organization's sytematic nomenclature to", "organization's sytematic nomenclature to human", "sytematic nomenclature to human genes", "to human genes the", "human genes the bicarbonate", "genes the bicarbonate transporters", "the bicarbonate transporters belong to", "bicarbonate transporters belong to the", "transporters belong to the slc4a", "belong to the slc4a and", "to the slc4a and slc26a", "the slc4a and slc26a families.", "slc4a and slc26a families. within", "and slc26a families. within slc4a", "families. within slc4a there", "within slc4a there are", "slc4a there are two", "there are two distinct subfamilies", "two distinct subfamilies functionally", "distinct subfamilies functionally corresponding", "subfamilies functionally corresponding to", "functionally corresponding to the electroneutral", "corresponding to the electroneutral cl", "to the electroneutral cl /hco3", "electroneutral cl /hco3 exchangers", "cl /hco3 exchangers and", "/hco3 exchangers and na+", "exchangers and na+ coupled hco3", "na+ coupled hco3 co", "coupled hco3 co transporters", "co transporters romero mf", "transporters romero mf et", "mf et al 2004", "al 2004 cordat", "2004 cordat e and", "cordat e and casey jr", "and casey jr 2009", "casey jr 2009 ." ] }, { "record_id": "GLY_000594_1_1373", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "425986", "r hsa", "hsa 425986", "r hsa 425986" ] }, { "record_id": "GLY_000594_1_1373", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sodium/proton exchangers", "the slc9", "slc9 gene", "gene family", "family encode", "encode proteins", "nhe or", "or nhx", "which exchange", "exchange sodium", "for protons", "electroneutrally. this", "this mechanism", "mechanism is", "is important", "important because", "because many", "many metabolic", "metabolic processes", "processes generate", "generate acids", "acids which", "which need", "need to", "to be", "be removed", "removed to", "to maintain", "maintain ph.", "ph. this", "this is", "is the", "the major", "major proton", "proton extruding", "extruding system", "system in", "in cells", "driven by", "by the", "the inward", "inward sodium", "sodium ion", "ion chemical", "chemical gradient.", "gradient. to", "to date", "there are", "are eleven", "eleven nhe", "nhe genes", "nhe1 11.", "11. nhe1", "nhe1 5", "5 exchange", "exchange cations", "cations at", "at the", "the cell", "cell membrane.", "membrane. nhe6", "nhe6 9", "9 exchange", "at endosomal", "endosomal membranes", "membranes or", "or the", "the trans", "trans golgi", "golgi network", "network membranes.", "the slc9 gene", "slc9 gene family", "gene family encode", "family encode proteins", "proteins sodium/proton", "exchangers nhe", "nhe or nhx", "nhx which", "which exchange sodium", "sodium influx", "influx for", "protons efflux", "efflux electroneutrally.", "electroneutrally. this mechanism", "this mechanism is", "mechanism is important", "is important because", "important because many", "because many metabolic", "many metabolic processes", "metabolic processes generate", "processes generate acids", "generate acids which", "acids which need", "which need to", "need to be", "to be removed", "be removed to", "removed to maintain", "to maintain ph.", "maintain ph. this", "ph. this is", "this is the", "is the major", "the major proton", "major proton extruding", "proton extruding system", "extruding system in", "system in cells", "cells driven", "driven by the", "by the inward", "the inward sodium", "inward sodium ion", "sodium ion chemical", "ion chemical gradient.", "chemical gradient. to", "gradient. to date", "date there", "there are eleven", "are eleven nhe", "eleven nhe genes", "genes nhe1", "nhe1 11. nhe1", "11. nhe1 5", "nhe1 5 exchange", "5 exchange cations", "exchange cations at", "cations at the", "at the cell", "the cell membrane.", "cell membrane. nhe6", "membrane. nhe6 9", "nhe6 9 exchange", "9 exchange cations", "cations at endosomal", "at endosomal membranes", "endosomal membranes or", "membranes or the", "or the trans", "the trans golgi", "trans golgi network", "golgi network membranes.", "the slc9 gene family", "slc9 gene family encode", "gene family encode proteins", "encode proteins sodium/proton", "proteins sodium/proton exchangers", "sodium/proton exchangers nhe", "exchangers nhe or", "or nhx which", "nhx which exchange", "exchange sodium influx", "influx for protons", "for protons efflux", "efflux electroneutrally. this", "electroneutrally. this mechanism is", "this mechanism is important", "mechanism is important because", "is important because many", "important because many metabolic", "because many metabolic processes", "many metabolic processes generate", "metabolic processes generate acids", "processes generate acids which", "generate acids which need", "acids which need to", "which need to be", "need to be removed", "to be removed to", "be removed to maintain", "removed to maintain ph.", "to maintain ph. this", "maintain ph. this is", "ph. this is the", "this is the major", "is the major proton", "the major proton extruding", "major proton extruding system", "proton extruding system in", "extruding system in cells", "in cells driven", "cells driven by", "driven by the inward", "by the inward sodium", "the inward sodium ion", "inward sodium ion chemical", "sodium ion chemical gradient.", "ion chemical gradient. to", "chemical gradient. to date", "to date there", "date there are", "there are eleven nhe", "are eleven nhe genes", "nhe genes nhe1", "genes nhe1 11.", "nhe1 11. nhe1 5", "11. nhe1 5 exchange", "nhe1 5 exchange cations", "5 exchange cations at", "exchange cations at the", "cations at the cell", "at the cell membrane.", "the cell membrane. nhe6", "cell membrane. nhe6 9", "membrane. nhe6 9 exchange", "nhe6 9 exchange cations", "9 exchange cations at", "exchange cations at endosomal", "cations at endosomal membranes", "at endosomal membranes or", "endosomal membranes or the", "membranes or the trans", "or the trans golgi", "the trans golgi network", "trans golgi network membranes.", "the slc9 gene family encode", "slc9 gene family encode proteins", "family encode proteins sodium/proton", "encode proteins sodium/proton exchangers", "sodium/proton exchangers nhe or", "exchangers nhe or nhx", "nhe or nhx which", "or nhx which exchange", "nhx which exchange sodium", "which exchange sodium influx", "sodium influx for", "protons efflux electroneutrally.", "efflux electroneutrally. this mechanism", "electroneutrally. this mechanism is important", "this mechanism is important because", "mechanism is important because many", "is important because many metabolic", "important because many metabolic processes", "because many metabolic processes generate", "many metabolic processes generate acids", "metabolic processes generate acids which", "processes generate acids which need", "generate acids which need to", "acids which need to be", "which need to be removed", "need to be removed to", "to be removed to maintain", "be removed to maintain ph.", "removed to maintain ph. this", "to maintain ph. this is", "maintain ph. this is the", "ph. this is the major", "this is the major proton", "is the major proton extruding", "the major proton extruding system", "major proton extruding system in", "proton extruding system in cells", "system in cells driven", "in cells driven by", "cells driven by the", "driven by the inward sodium", "by the inward sodium ion", "the inward sodium ion chemical", "inward sodium ion chemical gradient.", "sodium ion chemical gradient. to", "ion chemical gradient. to date", "gradient. to date there", "to date there are", "date there are eleven", "there are eleven nhe genes", "eleven nhe genes nhe1", "nhe genes nhe1 11.", "genes nhe1 11. nhe1", "nhe1 11. nhe1 5 exchange", "11. nhe1 5 exchange cations", "nhe1 5 exchange cations at", "5 exchange cations at the", "exchange cations at the cell", "cations at the cell membrane.", "at the cell membrane. nhe6", "the cell membrane. nhe6 9", "cell membrane. nhe6 9 exchange", "membrane. nhe6 9 exchange cations", "nhe6 9 exchange cations at", "9 exchange cations at endosomal", "exchange cations at endosomal membranes", "cations at endosomal membranes or", "at endosomal membranes or the", "endosomal membranes or the trans", "membranes or the trans golgi", "or the trans golgi network", "the trans golgi network membranes." ] }, { "record_id": "GLY_000594_1_1374", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "432142", "r hsa", "hsa 432142", "r hsa 432142" ] }, { "record_id": "GLY_000594_1_1374", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "platelet sensitization", "sensitization by", "by ldl", "platelet sensitization by", "sensitization by ldl", "platelet sensitization by ldl", "physiological concentrations", "of low", "low density", "density lipoprotein", "enhance platelet", "platelet aggregation", "aggregation responses", "responses initiated", "initiated by", "by thrombin", "and adp.", "adp. this", "this enhancement", "enhancement involves", "involves the", "the rapid", "rapid phosphorylation", "phosphorylation of", "of p38", "p38 mitogen", "mitogen activated", "activated protein", "protein kinase", "at thr180", "thr180 and", "and tyr182.", "tyr182. the", "the receptor", "receptor for", "for ldl", "ldl is", "is apoer2", "a splice", "splice variant", "variant of", "of the", "the classical", "classical apoe", "apoe receptor.", "receptor. apoer2", "apoer2 stimulation", "stimulation leads", "leads to", "to association", "association of", "the src", "src family", "family kinase", "kinase fgr", "fgr which", "which is", "is probably", "probably responsible", "responsible for", "for subsequent", "subsequent phosphorylation", "of p38mapk.", "p38mapk. this", "this stimulation", "stimulation is", "is transient", "transient because", "because ldl", "ldl also", "also increases", "increases the", "the activity", "activity of", "of pecam", "pecam 1", "which stimulates", "stimulates phosphatases", "phosphatases that", "that dephosphorylate", "dephosphorylate p38mapk.", "concentrations 1g/l", "1g/l of", "of low density", "low density lipoprotein", "lipoprotein ldl", "ldl enhance", "enhance platelet aggregation", "platelet aggregation responses", "aggregation responses initiated", "responses initiated by", "initiated by thrombin", "thrombin collagen", "collagen and", "and adp. this", "adp. this enhancement", "this enhancement involves", "enhancement involves the", "involves the rapid", "the rapid phosphorylation", "rapid phosphorylation of", "phosphorylation of p38", "of p38 mitogen", "p38 mitogen activated", "mitogen activated protein", "activated protein kinase", "kinase p38mapk", "p38mapk at", "at thr180 and", "thr180 and tyr182.", "and tyr182. the", "tyr182. the receptor", "the receptor for", "receptor for ldl", "for ldl is", "ldl is apoer2", "apoer2 a", "a splice variant", "splice variant of", "variant of the", "of the classical", "the classical apoe", "classical apoe receptor.", "apoe receptor. apoer2", "receptor. apoer2 stimulation", "apoer2 stimulation leads", "stimulation leads to", "leads to association", "to association of", "association of the", "of the src", "the src family", "src family kinase", "family kinase fgr", "kinase fgr which", "fgr which is", "which is probably", "is probably responsible", "probably responsible for", "responsible for subsequent", "for subsequent phosphorylation", "subsequent phosphorylation of", "phosphorylation of p38mapk.", "of p38mapk. this", "p38mapk. this stimulation", "this stimulation is", "stimulation is transient", "is transient because", "transient because ldl", "because ldl also", "ldl also increases", "also increases the", "increases the activity", "the activity of", "activity of pecam", "of pecam 1", "1 which", "which stimulates phosphatases", "stimulates phosphatases that", "phosphatases that dephosphorylate", "that dephosphorylate p38mapk.", "physiological concentrations 1g/l", "1g/l of low", "of low density lipoprotein", "density lipoprotein ldl", "ldl enhance platelet", "enhance platelet aggregation responses", "platelet aggregation responses initiated", "aggregation responses initiated by", "responses initiated by thrombin", "by thrombin collagen", "collagen and adp.", "and adp. this enhancement", "adp. this enhancement involves", "this enhancement involves the", "enhancement involves the rapid", "involves the rapid phosphorylation", "the rapid phosphorylation of", "rapid phosphorylation of p38", "phosphorylation of p38 mitogen", "of p38 mitogen activated", "p38 mitogen activated protein", "mitogen activated protein kinase", "protein kinase p38mapk", "p38mapk at thr180", "at thr180 and tyr182.", "thr180 and tyr182. the", "and tyr182. the receptor", "tyr182. the receptor for", "the receptor for ldl", "receptor for ldl is", "for ldl is apoer2", "is apoer2 a", "apoer2 a splice", "a splice variant of", "splice variant of the", "variant of the classical", "of the classical apoe", "the classical apoe receptor.", "classical apoe receptor. apoer2", "apoe receptor. apoer2 stimulation", "receptor. apoer2 stimulation leads", "apoer2 stimulation leads to", "stimulation leads to association", "leads to association of", "to association of the", "association of the src", "of the src family", "the src family kinase", "src family kinase fgr", "family kinase fgr which", "kinase fgr which is", "fgr which is probably", "which is probably responsible", "is probably responsible for", "probably responsible for subsequent", "responsible for subsequent phosphorylation", "for subsequent phosphorylation of", "subsequent phosphorylation of p38mapk.", "phosphorylation of p38mapk. this", "of p38mapk. this stimulation", "p38mapk. this stimulation is", "this stimulation is transient", "stimulation is transient because", "is transient because ldl", "transient because ldl also", "because ldl also increases", "ldl also increases the", "also increases the activity", "increases the activity of", "the activity of pecam", "activity of pecam 1", "pecam 1 which", "1 which stimulates", "which stimulates phosphatases that", "stimulates phosphatases that dephosphorylate", "phosphatases that dephosphorylate p38mapk.", "concentrations 1g/l of", "1g/l of low density", "low density lipoprotein ldl", "lipoprotein ldl enhance", "ldl enhance platelet aggregation", "enhance platelet aggregation responses initiated", "platelet aggregation responses initiated by", "aggregation responses initiated by thrombin", "initiated by thrombin collagen", "thrombin collagen and", "collagen and adp. this", "and adp. this enhancement involves", "adp. this enhancement involves the", "this enhancement involves the rapid", "enhancement involves the rapid phosphorylation", "involves the rapid phosphorylation of", "the rapid phosphorylation of p38", "rapid phosphorylation of p38 mitogen", "phosphorylation of p38 mitogen activated", "of p38 mitogen activated protein", "p38 mitogen activated protein kinase", "activated protein kinase p38mapk", "kinase p38mapk at", "p38mapk at thr180 and", "at thr180 and tyr182. the", "thr180 and tyr182. the receptor", "and tyr182. the receptor for", "tyr182. the receptor for ldl", "the receptor for ldl is", "receptor for ldl is apoer2", "ldl is apoer2 a", "is apoer2 a splice", "apoer2 a splice variant", "a splice variant of the", "splice variant of the classical", "variant of the classical apoe", "of the classical apoe receptor.", "the classical apoe receptor. apoer2", "classical apoe receptor. apoer2 stimulation", "apoe receptor. apoer2 stimulation leads", "receptor. apoer2 stimulation leads to", "apoer2 stimulation leads to association", "stimulation leads to association of", "leads to association of the", "to association of the src", "association of the src family", "of the src family kinase", "the src family kinase fgr", "src family kinase fgr which", "family kinase fgr which is", "kinase fgr which is probably", "fgr which is probably responsible", "which is probably responsible for", "is probably responsible for subsequent", "probably responsible for subsequent phosphorylation", "responsible for subsequent phosphorylation of", "for subsequent phosphorylation of p38mapk.", "subsequent phosphorylation of p38mapk. this", "phosphorylation of p38mapk. this stimulation", "of p38mapk. this stimulation is", "p38mapk. this stimulation is transient", "this stimulation is transient because", "stimulation is transient because ldl", "is transient because ldl also", "transient because ldl also increases", "because ldl also increases the", "ldl also increases the activity", "also increases the activity of", "increases the activity of pecam", "the activity of pecam 1", "of pecam 1 which", "pecam 1 which stimulates", "1 which stimulates phosphatases", "which stimulates phosphatases that dephosphorylate", "stimulates phosphatases that dephosphorylate p38mapk." ] }, { "record_id": "GLY_000594_1_1375", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4341670", "r hsa", "hsa 4341670", "r hsa 4341670" ] }, { "record_id": "GLY_000594_1_1375", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective neu1", "neu1 causes", "causes sialidosis", "defective neu1 causes", "neu1 causes sialidosis", "defective neu1 causes sialidosis", "sialidases have", "have important", "important roles", "roles in", "in the", "the degradation", "degradation of", "of glycoconjugates", "glycoconjugates by", "by removing", "removing terminal", "terminal sialic", "sialic acid", "acid residues.
              defects", "residues.
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              defects", "acid residues.
              defects in", "residues.
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              defects", "sialic acid residues.
              defects in", "acid residues.
              defects in sialidase", "residues.
              defects in sialidase 1", "sialidase 1 neu1", "neu1 cause sialidosis", "cause sialidosis a", "sialidosis a lysosomal", "a lysosomal storage disease", "lysosomal storage disease characterised", "storage disease characterised by", "disease characterised by the", "characterised by the progressive", "by the progressive lysosomal", "the progressive lysosomal storage", "progressive lysosomal storage of", "lysosomal storage of sialidated", "storage of sialidated glycopeptides", "of sialidated glycopeptides and", "sialidated glycopeptides and oligosaccharides", "glycopeptides and oligosaccharides and", "and oligosaccharides and the", "oligosaccharides and the accumulation", "and the accumulation and", "the accumulation and excretion", "accumulation and excretion of", "and excretion of n", "excretion of n acetylneuraminic", "of n acetylneuraminic acid", "acetylneuraminic acid neu5ac", "neu5ac covalently linked", "covalently linked 'bound'", "glycoconjugates lowden &", "lowden & o'brien 1979", "& o'brien 1979 .", "o'brien 1979 . the", "1979 . the sialidoses", ". the sialidoses are", "the sialidoses are distinct", "sialidoses are distinct from", "are distinct from the", "distinct from the sialurias", "from the sialurias in", "the sialurias in which", "sialurias in which there", "in which there is", "which there is storage", "there is storage and", "is storage and excretion", "storage and excretion of", "and excretion of 'free'", "excretion of 'free' neu5ac.", "of 'free' neu5ac. sialidosis", "'free' neu5ac. sialidosis manifests", "neu5ac. sialidosis manifests into", "sialidosis manifests into types", "manifests into types i", "into types i and", "types i and ii", "i and ii forms.", "and ii forms. type", "ii forms. type i", "forms. type i is", "type i is the", "i is the milder", "is the milder form", "milder form also", "form also known", "also known as the", "known as the 'normosomatic'", "as the 'normosomatic' type", "the 'normosomatic' type or", "'normosomatic' type or the", "type or the cherry", "or the cherry red", "the cherry red spot", "cherry red spot myoclonus", "red spot myoclonus syndrome.", "spot myoclonus syndrome. sialidosis", "myoclonus syndrome. sialidosis type", "syndrome. sialidosis type ii", "sialidosis type ii is", "type ii is the", "ii is the more", "is the more severe", "the more severe form", "more severe form with", "severe form with an", "form with an earlier", "with an earlier onset", "earlier onset and", "onset and is", "and is also known", "is also known as", "known as the 'dysmorphic'", "as the 'dysmorphic' type.", "sialidases have important roles in", "have important roles in the", "important roles in the degradation", "roles in the degradation of", "in the degradation of glycoconjugates", "the degradation of glycoconjugates by", "degradation of glycoconjugates by removing", "of glycoconjugates by removing terminal", "glycoconjugates by removing terminal sialic", "by removing terminal sialic acid", "removing terminal sialic acid residues.
              defects", "terminal sialic acid residues.
              defects in", "sialic acid residues.
              defects in sialidase", "acid residues.
              defects in sialidase 1", "in sialidase 1 neu1", "1 neu1 cause", "cause sialidosis a lysosomal", "sialidosis a lysosomal storage", "a lysosomal storage disease characterised", "lysosomal storage disease characterised by", "storage disease characterised by the", "disease characterised by the progressive", "characterised by the progressive lysosomal", "by the progressive lysosomal storage", "the progressive lysosomal storage of", "progressive lysosomal storage of sialidated", "lysosomal storage of sialidated glycopeptides", "storage of sialidated glycopeptides and", "of sialidated glycopeptides and oligosaccharides", "sialidated glycopeptides and oligosaccharides and", "glycopeptides and oligosaccharides and the", "and oligosaccharides and the accumulation", "oligosaccharides and the accumulation and", "and the accumulation and excretion", "the accumulation and excretion of", "accumulation and excretion of n", "and excretion of n acetylneuraminic", "excretion of n acetylneuraminic acid", "n acetylneuraminic acid neu5ac", "acid neu5ac covalently", "linked 'bound' glycoconjugates", "'bound' glycoconjugates lowden", "glycoconjugates lowden & o'brien", "lowden & o'brien 1979 .", "& o'brien 1979 . the", "o'brien 1979 . the sialidoses", "1979 . the sialidoses are", ". the sialidoses are distinct", "the sialidoses are distinct from", "sialidoses are distinct from the", "are distinct from the sialurias", "distinct from the sialurias in", "from the sialurias in which", "the sialurias in which there", "sialurias in which there is", "in which there is storage", "which there is storage and", "there is storage and excretion", "is storage and excretion of", "storage and excretion of 'free'", "and excretion of 'free' neu5ac.", "excretion of 'free' neu5ac. sialidosis", "of 'free' neu5ac. sialidosis manifests", "'free' neu5ac. sialidosis manifests into", "neu5ac. sialidosis manifests into types", "sialidosis manifests into types i", "manifests into types i and", "into types i and ii", "types i and ii forms.", "i and ii forms. type", "and ii forms. type i", "ii forms. type i is", "forms. type i is the", "type i is the milder", "i is the milder form", "the milder form also", "milder form also known", "form also known as", "also known as the 'normosomatic'", "known as the 'normosomatic' type", "as the 'normosomatic' type or", "the 'normosomatic' type or the", "'normosomatic' type or the cherry", "type or the cherry red", "or the cherry red spot", "the cherry red spot myoclonus", "cherry red spot myoclonus syndrome.", "red spot myoclonus syndrome. sialidosis", "spot myoclonus syndrome. sialidosis type", "myoclonus syndrome. sialidosis type ii", "syndrome. sialidosis type ii is", "sialidosis type ii is the", "type ii is the more", "ii is the more severe", "is the more severe form", "the more severe form with", "more severe form with an", "severe form with an earlier", "form with an earlier onset", "an earlier onset and", "earlier onset and is", "onset and is also", "and is also known as", "is also known as the", "also known as the 'dysmorphic'", "known as the 'dysmorphic' type." ] }, { "record_id": "GLY_000594_1_1376", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "442720", "r hsa", "hsa 442720", "r hsa 442720" ] }, { "record_id": "GLY_000594_1_1376", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "creb1 phosphorylation", "phosphorylation through", "through the", "the activation", "activation of", "of adenylate", "adenylate cyclase", "creb1 phosphorylation through", "phosphorylation through the", "through the activation", "the activation of", "activation of adenylate", "of adenylate cyclase", "creb1 phosphorylation through the", "phosphorylation through the activation", "through the activation of", "the activation of adenylate", "activation of adenylate cyclase", "creb1 phosphorylation through the activation", "phosphorylation 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signal", "mediated signal transduction", "transduction leading", "leading to the", "to the activation", "activation of pka", "of pka and", "pka and phosphorylation", "and phosphorylation and", "phosphorylation and activation", "and activation of", "activation of creb1", "of creb1 induced", "creb1 induced transcription", "transcription masada", "masada et al.", "et al. 2012", "2012 chetkovich", "chetkovich et al.", "et al. 1991", "1991 chetkovich", "chetkovich and sweatt", "and sweatt 1993", "ca2+ influx through activated", "influx through activated nmda", "through activated nmda receptors", "activated nmda receptors in", "nmda receptors in the", "receptors in the post", "in the post synaptic", "the post synaptic neurons", "post synaptic neurons activates", "synaptic neurons activates adenylate", "neurons activates adenylate cyclase", "activates adenylate cyclase mediated", "adenylate cyclase mediated signal", "cyclase mediated signal transduction", "signal transduction leading", "transduction leading to", "leading to the activation", "to the activation of", "the activation of pka", "activation of pka and", "of pka and phosphorylation", "pka and phosphorylation and", "and phosphorylation and activation", "phosphorylation and activation of", "and activation of creb1", "activation of creb1 induced", "of creb1 induced transcription", "induced transcription masada", "transcription masada et", "masada et al. 2012", "al. 2012 chetkovich", "2012 chetkovich et", "chetkovich et al. 1991", "al. 1991 chetkovich", "1991 chetkovich and", "chetkovich and sweatt 1993", "ca2+ influx through activated nmda", "influx through activated nmda receptors", "through activated nmda receptors in", "activated nmda receptors in the", "nmda receptors in the post", "receptors in the post synaptic", "in the post synaptic neurons", "the post synaptic neurons activates", "post synaptic neurons activates adenylate", "synaptic neurons activates adenylate cyclase", "neurons activates adenylate cyclase mediated", "activates adenylate cyclase mediated signal", "adenylate cyclase mediated signal transduction", "mediated signal transduction leading", "signal transduction leading to", "transduction leading to the", "leading to the activation of", "to the activation of pka", "the activation of pka and", "activation of pka and phosphorylation", "of pka and phosphorylation and", "pka and phosphorylation and activation", "and phosphorylation and activation of", "phosphorylation and activation of creb1", "and activation of creb1 induced", "activation of creb1 induced transcription", "creb1 induced transcription masada", "induced transcription masada et", "transcription masada et al.", "et al. 2012 chetkovich", "al. 2012 chetkovich et", "2012 chetkovich et al.", "et al. 1991 chetkovich", "al. 1991 chetkovich and", "1991 chetkovich and sweatt" ] }, { "record_id": "GLY_000594_1_1377", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "442729", "r hsa", "hsa 442729", "r hsa 442729" ] }, { "record_id": "GLY_000594_1_1377", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "creb1 phosphorylation", "phosphorylation through", "through the", "the activation", "activation of", "of camkii/camkk/camkiv", "camkii/camkk/camkiv cascasde", "creb1 phosphorylation through", "phosphorylation through the", "through the activation", "the activation of", "activation of camkii/camkk/camkiv", "of camkii/camkk/camkiv cascasde", "creb1 phosphorylation through the", "phosphorylation through the activation", "through the activation of", "the activation of camkii/camkk/camkiv", "activation of camkii/camkk/camkiv cascasde", "creb1 phosphorylation through the activation", "phosphorylation through the activation of", "through the activation of camkii/camkk/camkiv", "the activation of camkii/camkk/camkiv cascasde", "in addition", "addition to", "to inducing", "inducing long", "long term", "term potentiation", "nmda receptor", "receptor mediated", "mediated activation", "of camkii", "camkii leads", "leads to", "to transcriptional", "transcriptional changes", "changes that", "that are", "are implicated", "implicated in", "in ltp", "ltp maintenance", "reviewed by", "by miyamoto", "miyamoto 2006", "2006 .", ". camkii", "camkii gamma", "isoform is", "is involved", "involved in", "in nuclear", "nuclear shuttling", "shuttling of", "of the", "the calcium/calmodulin", "calcium/calmodulin complex", "which enables", "enables camkk", "camkk mediated", "the nuclear", "nuclear calcium/calmodulin", "calcium/calmodulin dependent", "dependent kinase", "kinase camkiv", "camk4 .", ". activated", "activated camkiv", "camkiv phosphorylates", "phosphorylates the", "the transcription", "transcription factor", "factor creb1", "creb1 and", "and activates", "activates creb1", "creb1 mediated", "mediated transcription", "ma et", "et al.", "al. 2014", "cohen et", "al. 2018", "2018 .", "in addition to", "addition to inducing", "to inducing long", "inducing long term", "long term potentiation", "potentiation ltp", "nmda receptor mediated", "receptor mediated activation", "mediated activation of", "activation of camkii", "of camkii leads", "camkii leads to", "leads to transcriptional", "to transcriptional changes", "transcriptional changes that", "changes that are", "that are implicated", "are implicated in", "implicated in ltp", "in ltp maintenance", "maintenance reviewed", "reviewed by miyamoto", "by miyamoto 2006", "miyamoto 2006 .", "2006 . camkii", ". camkii gamma", "gamma camk2g", "camk2g isoform", "isoform is involved", "is involved in", "involved in nuclear", "in nuclear shuttling", "nuclear shuttling of", "shuttling of the", "of the calcium/calmodulin", "the calcium/calmodulin complex", "complex calm1:4xca2+", "which enables camkk", "enables camkk mediated", "camkk mediated activation", "activation of the", "of the nuclear", "the nuclear calcium/calmodulin", "nuclear calcium/calmodulin dependent", "calcium/calmodulin dependent kinase", "dependent kinase camkiv", "camkiv camk4", "camk4 . activated", ". activated camkiv", "activated camkiv phosphorylates", "camkiv phosphorylates the", "phosphorylates the transcription", "the transcription factor", "transcription factor creb1", "factor creb1 and", "creb1 and activates", "and activates creb1", "activates creb1 mediated", "creb1 mediated transcription", "transcription ma", "ma et al.", "et al. 2014", "2014 cohen", "cohen et al.", "et al. 2018", "al. 2018 .", "in addition to inducing", "addition to inducing long", "to inducing long term", "inducing long term potentiation", "term potentiation ltp", "ltp nmda", "nmda receptor mediated activation", "receptor mediated activation of", "mediated activation of camkii", "activation of camkii leads", "of camkii leads to", "camkii leads to transcriptional", "leads to transcriptional changes", "to transcriptional changes that", "transcriptional changes that are", "changes that are implicated", "that are implicated in", "are implicated in ltp", "implicated in ltp maintenance", "ltp maintenance reviewed", "maintenance reviewed by", "reviewed by miyamoto 2006", "by miyamoto 2006 .", "miyamoto 2006 . camkii", "2006 . camkii gamma", "camkii gamma camk2g", "camk2g isoform is", "isoform is involved in", "is involved in nuclear", "involved in nuclear shuttling", "in nuclear shuttling of", "nuclear shuttling of the", "shuttling of the calcium/calmodulin", "of the calcium/calmodulin complex", "calcium/calmodulin complex calm1:4xca2+", "calm1:4xca2+ which", "which enables camkk mediated", "enables camkk mediated activation", "camkk mediated activation of", "mediated activation of the", "activation of the nuclear", "of the nuclear calcium/calmodulin", "the nuclear calcium/calmodulin dependent", "nuclear calcium/calmodulin dependent kinase", "calcium/calmodulin dependent kinase camkiv", "kinase camkiv camk4", "camkiv camk4 .", "camk4 . activated camkiv", ". activated camkiv phosphorylates", "activated camkiv phosphorylates the", "camkiv phosphorylates the transcription", "phosphorylates the transcription factor", "the transcription factor creb1", "transcription factor creb1 and", "factor creb1 and activates", "creb1 and activates creb1", "and activates creb1 mediated", "activates creb1 mediated transcription", "mediated transcription ma", "transcription ma et", "ma et al. 2014", "al. 2014 cohen", "2014 cohen et", "cohen et al. 2018", "et al. 2018 .", "in addition to inducing long", "addition to inducing long term", "to inducing long term potentiation", "long term potentiation ltp", "ltp nmda receptor", "nmda receptor mediated activation of", "receptor mediated activation of camkii", "mediated activation of camkii leads", "activation of camkii leads to", "of camkii leads to transcriptional", "camkii leads to transcriptional changes", "leads to transcriptional changes that", "to transcriptional changes that are", "transcriptional changes that are implicated", "changes that are implicated in", "that are implicated in ltp", "are implicated in ltp maintenance", "in ltp maintenance reviewed", "ltp maintenance reviewed by", "maintenance reviewed by miyamoto", "reviewed by miyamoto 2006 .", "by miyamoto 2006 . camkii", "miyamoto 2006 . camkii gamma", ". camkii gamma camk2g", "gamma camk2g isoform", "camk2g isoform is involved", "isoform is involved in nuclear", "is involved in nuclear shuttling", "involved in nuclear shuttling of", "in nuclear shuttling of the", "nuclear shuttling of the calcium/calmodulin", "shuttling of the calcium/calmodulin complex", "the calcium/calmodulin complex calm1:4xca2+", "calm1:4xca2+ which enables", "which enables camkk mediated activation", "enables camkk mediated activation of", "camkk mediated activation of the", "mediated activation of the nuclear", "activation of the nuclear calcium/calmodulin", "of the nuclear calcium/calmodulin dependent", "the nuclear calcium/calmodulin dependent kinase", "nuclear calcium/calmodulin dependent kinase camkiv", "dependent kinase camkiv camk4", "kinase camkiv camk4 .", "camkiv camk4 . activated", "camk4 . activated camkiv phosphorylates", ". activated camkiv phosphorylates the", "activated camkiv phosphorylates the transcription", "camkiv phosphorylates the transcription factor", "phosphorylates the transcription factor creb1", "the transcription factor creb1 and", "transcription factor creb1 and activates", "factor creb1 and activates creb1", "creb1 and activates creb1 mediated", "and activates creb1 mediated transcription", "creb1 mediated transcription ma", "mediated transcription ma et", "transcription ma et al.", "et al. 2014 cohen", "al. 2014 cohen et", "2014 cohen et al.", "cohen et al. 2018 ." ] }, { "record_id": "GLY_000594_1_1378", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "442742", "r hsa", "hsa 442742", "r hsa 442742" ] }, { "record_id": "GLY_000594_1_1378", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "creb1 phosphorylation", "phosphorylation through", "through nmda", "nmda receptor", "receptor mediated", "mediated activation", "activation of", "of ras", "ras signaling", "creb1 phosphorylation through", "phosphorylation through nmda", "through nmda receptor", "nmda receptor mediated", "receptor mediated activation", "mediated activation of", "activation of ras", "of ras signaling", "creb1 phosphorylation through nmda", "phosphorylation through nmda receptor", "through nmda receptor mediated", "nmda receptor mediated activation", "receptor mediated activation of", "mediated activation of ras", "activation of ras signaling", "creb1 phosphorylation through nmda receptor", "phosphorylation through nmda receptor mediated", "through nmda receptor mediated activation", "nmda receptor mediated activation of", "receptor mediated activation of ras", "mediated activation of ras signaling", "ca2+ influx", "influx through", "through the", "the nmda", "receptor activates", "activates ras", "ras guanyl", "guanyl nucleotide", "nucleotide exchange", "exchange factor", "factor rasgrf", "which promotes", "promotes formation", "formation of", "of active", "active ras:gtp", "ras:gtp complexes", "anborgh et", "et al.", "al. 1999", "krapivinsky et", "al. 2003", "2003 .", ". camkii", "also activated", "activated by", "by nmda", "mediated ca2+", "can contribute", "contribute to", "to activation", "of ras/raf/mapk", "ras/raf/mapk signaling", "signaling by", "by phosphorylation", "phosphorylation of", "of raf1", "salzano et", "al. 2012", "2012 .", ". erks", "mapk1 and", "and mapk3", "activated downstream", "downstream of", "phosphorylate ribosomal", "ribosomal protein", "protein s6", "s6 kinases", "initiating activation", "of rsks", "reviewed by", "by anjum", "anjum and", "and blenis", "blenis 2012", ". activated", "activated rsks", "rsks phosphorylate", "phosphorylate the", "the transcription", "transcription factor", "factor creb1", "creb1 at", "at serine", "serine residue", "residue s133", "thus stimulating", "stimulating creb1", "creb1 mediated", "mediated transcription", "de cesare", "cesare et", "al. 1998", "harum et", "al. 2001", "schinelli et", "song et", "ca2+ influx through", "influx through the", "through the nmda", "the nmda receptor", "nmda receptor activates", "receptor activates ras", "activates ras guanyl", "ras guanyl nucleotide", "guanyl nucleotide exchange", "nucleotide exchange factor", "exchange factor rasgrf", "rasgrf which", "which promotes formation", "promotes formation of", "formation of active", "of active ras:gtp", "active ras:gtp complexes", "complexes anborgh", "anborgh et al.", "et al. 1999", "1999 krapivinsky", "krapivinsky et al.", "et al. 2003", "al. 2003 .", "2003 . camkii", "camkii also", "also activated by", "activated by nmda", "by nmda receptor", "receptor mediated ca2+", "mediated ca2+ influx", "influx can", "can contribute to", "contribute to activation", "to activation of", "activation of ras/raf/mapk", "of ras/raf/mapk signaling", "ras/raf/mapk signaling by", "signaling by phosphorylation", "by phosphorylation of", "phosphorylation of raf1", "raf1 salzano", "salzano et al.", "et al. 2012", "al. 2012 .", "2012 . erks", "erks mapk1", "mapk1 and mapk3", "activated downstream of", "downstream of ras", "signaling phosphorylate", "phosphorylate ribosomal protein", "ribosomal protein s6", "protein s6 kinases", "kinases rsks", "initiating activation of", "activation of rsks", "rsks reviewed", "reviewed by anjum", "by anjum and", "anjum and blenis", "and blenis 2012", "blenis 2012 .", "2012 . activated", ". activated rsks", "activated rsks phosphorylate", "rsks phosphorylate the", "phosphorylate the transcription", "the transcription factor", "transcription factor creb1", "factor creb1 at", "creb1 at serine", "at serine residue", "serine residue s133", "s133 thus", "thus stimulating creb1", "stimulating creb1 mediated", "creb1 mediated transcription", "transcription de", "de cesare et", "cesare et al.", "et al. 1998", "1998 harum", "harum et al.", "et al. 2001", "2001 schinelli", "schinelli et al.", "2001 song", "song et al.", "ca2+ influx through the", "influx through the nmda", "through the nmda receptor", "the nmda receptor activates", "nmda receptor activates ras", "receptor activates ras guanyl", "activates ras guanyl nucleotide", "ras guanyl nucleotide exchange", "guanyl nucleotide exchange factor", "nucleotide exchange factor rasgrf", "factor rasgrf which", "rasgrf which promotes", "which promotes formation of", "promotes formation of active", "formation of active ras:gtp", "of active ras:gtp complexes", "ras:gtp complexes anborgh", "complexes anborgh et", "anborgh et al. 1999", "al. 1999 krapivinsky", "1999 krapivinsky et", "krapivinsky et al. 2003", "et al. 2003 .", "al. 2003 . camkii", ". camkii also", "camkii also activated", "also activated by nmda", "activated by nmda receptor", "by nmda receptor mediated", "nmda receptor mediated ca2+", "receptor mediated ca2+ influx", "ca2+ influx can", "influx can contribute", "can contribute to activation", "contribute to activation of", "to activation of ras/raf/mapk", "activation of ras/raf/mapk signaling", "of ras/raf/mapk signaling by", "ras/raf/mapk signaling by phosphorylation", "signaling by phosphorylation of", "by phosphorylation of raf1", "of raf1 salzano", "raf1 salzano et", "salzano et al. 2012", "et al. 2012 .", "al. 2012 . erks", ". erks mapk1", "erks mapk1 and", "mapk3 activated", "activated downstream of ras", "downstream of ras signaling", "ras signaling phosphorylate", "signaling phosphorylate ribosomal", "phosphorylate ribosomal protein s6", "ribosomal protein s6 kinases", "s6 kinases rsks", "rsks initiating", "initiating activation of rsks", "of rsks reviewed", "rsks reviewed by", "reviewed by anjum and", "by anjum and blenis", "anjum and blenis 2012", "and blenis 2012 .", "blenis 2012 . activated", "2012 . activated rsks", ". activated rsks phosphorylate", "activated rsks phosphorylate the", "rsks phosphorylate the transcription", "phosphorylate the transcription factor", "the transcription factor creb1", "transcription factor creb1 at", "factor creb1 at serine", "creb1 at serine residue", "at serine residue s133", "residue s133 thus", "s133 thus stimulating", "thus stimulating creb1 mediated", "stimulating creb1 mediated transcription", "mediated transcription de", "transcription de cesare", "de cesare et al.", "cesare et al. 1998", "al. 1998 harum", "1998 harum et", "harum et al. 2001", "al. 2001 schinelli", "2001 schinelli et", "schinelli et al. 2001", "al. 2001 song", "2001 song et", "song et al. 2003", "ca2+ influx through the nmda", "influx through the nmda receptor", "through the nmda receptor activates", "the nmda receptor activates ras", "nmda receptor activates ras guanyl", "receptor activates ras guanyl nucleotide", "activates ras guanyl nucleotide exchange", "ras guanyl nucleotide exchange factor", "guanyl nucleotide exchange factor rasgrf", "exchange factor rasgrf which", "factor rasgrf which promotes", "rasgrf which promotes formation", "which promotes formation of active", "promotes formation of active ras:gtp", "formation of active ras:gtp complexes", "active ras:gtp complexes anborgh", "ras:gtp complexes anborgh et", "complexes anborgh et al.", "et al. 1999 krapivinsky", "al. 1999 krapivinsky et", "1999 krapivinsky et al.", "krapivinsky et al. 2003 .", "et al. 2003 . camkii", "2003 . camkii also", ". camkii also activated", "camkii also activated by", "also activated by nmda receptor", "activated by nmda receptor mediated", "by nmda receptor mediated ca2+", "nmda receptor mediated ca2+ influx", "mediated ca2+ influx can", "ca2+ influx can contribute", "influx can contribute to", "can contribute to activation of", "contribute to activation of ras/raf/mapk", "to activation of ras/raf/mapk signaling", "activation of ras/raf/mapk signaling by", "of ras/raf/mapk signaling by phosphorylation", "ras/raf/mapk signaling by phosphorylation of", "signaling by phosphorylation of raf1", "phosphorylation of raf1 salzano", "of raf1 salzano et", "raf1 salzano et al.", "salzano et al. 2012 .", "et al. 2012 . erks", "2012 . erks mapk1", ". erks mapk1 and", "erks mapk1 and mapk3", "and mapk3 activated", "mapk3 activated downstream", "activated downstream of ras signaling", "of ras signaling phosphorylate", "ras signaling phosphorylate ribosomal", "signaling phosphorylate ribosomal protein", "phosphorylate ribosomal protein s6 kinases", "protein s6 kinases rsks", "rsks initiating activation", "activation of rsks reviewed", "of rsks reviewed by", "rsks reviewed by anjum", "reviewed by anjum and blenis", "by anjum and blenis 2012", "anjum and blenis 2012 .", "and blenis 2012 . activated", "blenis 2012 . activated rsks", "2012 . activated rsks phosphorylate", ". activated rsks phosphorylate the", "activated rsks phosphorylate the transcription", "rsks phosphorylate the transcription factor", "phosphorylate the transcription factor creb1", "the transcription factor creb1 at", "transcription factor creb1 at serine", "factor creb1 at serine residue", "creb1 at serine residue s133", "serine residue s133 thus", "residue s133 thus stimulating", "s133 thus stimulating creb1", "thus stimulating creb1 mediated transcription", "creb1 mediated transcription de", "mediated transcription de cesare", "transcription de cesare et", "de cesare et al. 1998", "et al. 1998 harum", "al. 1998 harum et", "1998 harum et al.", "et al. 2001 schinelli", "al. 2001 schinelli et", "2001 schinelli et al.", "et al. 2001 song", "al. 2001 song et", "2001 song et al.", "song et al. 2003 ." ] }, { "record_id": "GLY_000594_1_1379", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "444473", "r hsa", "hsa 444473", "r hsa 444473" ] }, { "record_id": "GLY_000594_1_1379", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formyl peptide", "peptide receptors", "receptors bind", "bind formyl", "formyl peptides", "peptides and", "and many", "many other", "other ligands", "formyl peptide receptors", "peptide receptors bind", "receptors bind formyl", "bind formyl peptides", "formyl peptides and", "peptides and many", "and many other", "many other ligands", "formyl peptide receptors bind", "peptide receptors bind formyl", "receptors bind formyl peptides", "bind formyl peptides and", "formyl peptides and many", "peptides and many other", "and many other ligands", "formyl peptide receptors bind formyl", "peptide receptors bind formyl peptides", "receptors bind formyl peptides and", "bind formyl peptides and many", "formyl peptides and many other", "peptides and many other ligands", "the formyl", "peptide receptor", "was defined", "defined pharmacologically", "pharmacologically in", "in 1976", "1976 as", "as a", "a high", "high 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              ", "
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              ", "proteins.
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              ", "g proteins.
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              ", "of g proteins.
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              all 3 receptors can", "all 3 receptors can be", "3 receptors can be activated", "receptors can be activated by", "can be activated by formyl", "be activated by formyl peptides", "activated by formyl peptides but", "by formyl peptides but also", "formyl peptides but also display", "peptides but also display affinities", "but also display affinities for", "also display affinities for a", "display affinities for a range", "affinities for a range of", "for a range of structurally", "a range of structurally diverse", "range of structurally diverse ligands." ] }, { "record_id": "GLY_000594_1_1380", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "444821", "r hsa", "hsa 444821", "r hsa 444821" ] }, { "record_id": "GLY_000594_1_1380", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "relaxin receptors", "relaxins are", "are part", "part of", "of a", "a family", "family of", "of peptide", "peptide hormones", "hormones that", "that diverged", "diverged from", "from insulin", "insulin in", "in early", "early vertebrate", "vertebrate evolution", "evolution to", "to form", "form the", "the insulin", "insulin like", "like peptides", "peptides and", "and relaxins", "now often", "often referred", "referred to", "to as", "as the", "the relaxin", "relaxin peptide", "peptide family.", "family. all", "all are", "are heterodimers", "both chains", "chains are", "are cleaved", "cleaved from", "from a", "a common", "common propeptide", "propeptide and", "and cross", "cross linked", "linked by", "by 2", "2 disulphide", "disulphide bonds.", "bonds. humans", "humans have", "have 3", "3 true", "true relaxins", "relaxins encoded", "encoded by", "by 3", "3 related", "related genes", "plus several", "several more", "more distantly", "distantly related", "related insulin", "like peptide", "peptide genes.", "genes. non", "non primates", "primates have", "have 2", "2 relaxin", "relaxin genes.", "genes. the", "the major", "major circulating", "circulating form", "form of", "of relaxin", "relaxin in", "in humans", "humans is", "is relaxin", "relaxin 2", "equivalent to", "to relaxin", "relaxin 1", "1 in", "in non", "non primates.", "primates. relaxin", "relaxin 3", "3 is", "is very", "very highly", "highly conserved.", "conserved. little", "little is", "is known", "known about", "about human", "human relaxin", "several of", "of the", "peptides have", "have no", "no known", "known receptor", "receptor or", "or function.", "function.
              ", "
              there", "there are", "are 4", "4 human", "human g", "g protein", "protein coupled", "coupled receptors", "receptors for", "for relaxin", "relaxin family", "family peptides.", "peptides. relaxin", "relaxin receptor", "receptor 1", "and relaxin", "receptor 2", "are also", "also known", "known as", "as lgr7", "lgr7 and", "and lgr8", "lgr8 respectively", "members of", "the lrr", "lrr containing", "containing g", "lgrs .", ". relaxin", "3 receptor", "are unrelated", "having more", "more homology", "homology with", "with small", "small peptide", "peptide receptors", "receptors such", "such as", "the somatostatin", "somatostatin receptors.", "relaxins are part", "are part of", "part of a", "of a family", "a family of", "family of peptide", "of peptide hormones", "peptide hormones that", "hormones that diverged", "that diverged from", "diverged from insulin", "from insulin in", "insulin in early", "in early vertebrate", "early vertebrate evolution", "vertebrate evolution to", "evolution to form", "to form the", "form the insulin", "the insulin like", "insulin like peptides", "like peptides and", "peptides and relaxins", "relaxins now", "now often referred", "often referred to", "referred to as", "to as the", "as the relaxin", "the relaxin peptide", "relaxin peptide family.", "peptide family. all", "family. all are", "all are heterodimers", "heterodimers both", "both chains are", "chains are cleaved", "are cleaved from", "cleaved from a", "from a common", "a common propeptide", "common propeptide and", "propeptide and cross", "and cross linked", "cross linked by", "linked by 2", "by 2 disulphide", "2 disulphide bonds.", "disulphide bonds. humans", "bonds. humans have", "humans have 3", "have 3 true", "3 true relaxins", "true relaxins encoded", "relaxins encoded by", "encoded by 3", "by 3 related", "3 related genes", "genes plus", "plus several more", "several more distantly", "more distantly related", "distantly related insulin", "related insulin like", "insulin like peptide", "like peptide genes.", "peptide genes. non", "genes. non primates", "non primates have", "primates have 2", "have 2 relaxin", "2 relaxin genes.", "relaxin genes. the", "genes. the major", "the major circulating", "major circulating form", "circulating form of", "form of relaxin", "of relaxin in", "relaxin in humans", "in humans is", "humans is relaxin", "is relaxin 2", "2 equivalent", "equivalent to relaxin", "to relaxin 1", "relaxin 1 in", "1 in non", "in non primates.", "non primates. relaxin", "primates. relaxin 3", "relaxin 3 is", "3 is very", "is very highly", "very highly conserved.", "highly conserved. little", "conserved. little is", "little is known", "is known about", "known about human", "about human relaxin", "human relaxin 1", "1 several", "several of the", "of the insulin", "like peptides have", "peptides have no", "have no known", "no known receptor", "known receptor or", "receptor or function.", "or function.
              ", "function.
              there", "
              there are", "there are 4", "are 4 human", "4 human g", "human g protein", "g protein coupled", "protein coupled receptors", "coupled receptors for", "receptors for relaxin", "for relaxin family", "relaxin family peptides.", "family peptides. relaxin", "peptides. relaxin receptor", "relaxin receptor 1", "1 rxfp1", "rxfp1 and", "and relaxin receptor", "relaxin receptor 2", "2 rxfp2", "rxfp2 are", "are also known", "also known as", "known as lgr7", "as lgr7 and", "lgr7 and lgr8", "and lgr8 respectively", "respectively members", "members of the", "of the lrr", "the lrr containing", "lrr containing g", "containing g protein", "receptors lgrs", "lgrs . relaxin", ". relaxin 3", "relaxin 3 receptor", "3 receptor 1", "1 rxfp3", "rxfp3 and", "and relaxin 3", "3 receptor 2", "2 rxfp4", "rxfp4 are", "unrelated having", "having more homology", "more homology with", "homology with small", "with small peptide", "small peptide receptors", "peptide receptors such", "receptors such as", "such as the", "as the somatostatin", "the somatostatin receptors.", "relaxins are part of", "are part of a", "part of a family", "of a family of", "a family of peptide", "family of peptide hormones", "of peptide hormones that", "peptide hormones that diverged", "hormones that diverged from", "that diverged from insulin", "diverged from insulin in", "from insulin in early", "insulin in early vertebrate", "in early vertebrate evolution", "early vertebrate evolution to", "vertebrate evolution to form", "evolution to form the", "to form the insulin", "form the insulin like", "the insulin like peptides", "insulin like peptides and", "like peptides and relaxins", "and relaxins now", "relaxins now often", "now often referred to", "often referred to as", "referred to as the", "to as the relaxin", "as the relaxin peptide", "the relaxin peptide family.", "relaxin peptide family. all", "peptide family. all are", "family. all are heterodimers", "are heterodimers both", "heterodimers both chains", "both chains are cleaved", "chains are cleaved from", "are cleaved from a", "cleaved from a common", "from a common propeptide", "a common propeptide and", "common propeptide and cross", "propeptide and cross linked", "and cross linked by", "cross linked by 2", "linked by 2 disulphide", "by 2 disulphide bonds.", "2 disulphide bonds. humans", "disulphide bonds. humans have", "bonds. humans have 3", "humans have 3 true", "have 3 true relaxins", "3 true relaxins encoded", "true relaxins encoded by", "relaxins encoded by 3", "encoded by 3 related", "by 3 related genes", "related genes plus", "genes plus several", "plus several more distantly", "several more distantly related", "more distantly related insulin", "distantly related insulin like", "related insulin like peptide", "insulin like peptide genes.", "like peptide genes. non", "peptide genes. non primates", "genes. non primates have", "non primates have 2", "primates have 2 relaxin", "have 2 relaxin genes.", "2 relaxin genes. the", "relaxin genes. the major", "genes. the major circulating", "the major circulating form", "major circulating form of", "circulating form of relaxin", "form of relaxin in", "of relaxin in humans", "relaxin in humans is", "in humans is relaxin", "humans is relaxin 2", "relaxin 2 equivalent", "2 equivalent to", "equivalent to relaxin 1", "to relaxin 1 in", "relaxin 1 in non", "1 in non primates.", "in non primates. relaxin", "non primates. relaxin 3", "primates. relaxin 3 is", "relaxin 3 is very", "3 is very highly", "is very highly conserved.", "very highly conserved. little", "highly conserved. little is", "conserved. little is known", "little is known about", "is known about human", "known about human relaxin", "about human relaxin 1", "relaxin 1 several", "1 several of", "several of the insulin", "of the insulin like", "insulin like peptides have", "like peptides have no", "peptides have no known", "have no known receptor", "no known receptor or", "known receptor or function.", "receptor or function.
              ", "or function.
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              ", "receptor or function.
              there", "or function.
              there are", "function.
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              there are 4 human", "there are 4 human g", "are 4 human g protein", "4 human g protein coupled", "human g protein coupled receptors", "g protein coupled receptors for", "protein coupled receptors for relaxin", "coupled receptors for relaxin family", "receptors for relaxin family peptides.", "for relaxin family peptides. relaxin", "relaxin family peptides. relaxin receptor", "family peptides. relaxin receptor 1", "relaxin receptor 1 rxfp1", "1 rxfp1 and", "rxfp1 and relaxin receptor", "relaxin receptor 2 rxfp2", "2 rxfp2 are", "rxfp2 are also known", "are also known as lgr7", "also known as lgr7 and", "known as lgr7 and lgr8", "as lgr7 and lgr8 respectively", "and lgr8 respectively members", "lgr8 respectively members of", "respectively members of the", "members of the lrr containing", "of the lrr containing g", "the lrr containing g protein", "lrr containing g protein coupled", "containing g protein coupled receptors", "protein coupled receptors lgrs", "coupled receptors lgrs .", "receptors lgrs . relaxin", "lgrs . relaxin 3 receptor", ". relaxin 3 receptor 1", "3 receptor 1 rxfp3", "1 rxfp3 and", "rxfp3 and relaxin 3", "and relaxin 3 receptor 2", "3 receptor 2 rxfp4", "2 rxfp4 are", "are unrelated having more", "unrelated having more homology", "having more homology with small", "more homology with small peptide", "homology with small peptide receptors", "with small peptide receptors such", "small peptide receptors such as", "peptide receptors such as the", "receptors such as the somatostatin", "such as the somatostatin receptors." ] }, { "record_id": "GLY_000594_1_1381", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "446203", "r hsa", "hsa 446203", "r hsa 446203" ] }, { "record_id": "GLY_000594_1_1381", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "asparagine n", "n linked", "linked glycosylation", "asparagine n linked", "n linked glycosylation", "asparagine n linked glycosylation", "glycosylation is", "is the", "the most", "most important", "important form", "form of", "of post", "post translational", "translational modification", "modification for", "for proteins", "proteins synthesized", "synthesized and", "and folded", "folded in", "in the", "the endoplasmic", "endoplasmic reticulum", "stanley et", "et al.", "al. 2009", "2009 .", ". an", "an early", "early study", "study in", "in 1999", "1999 revealed", "revealed that", "that about", "about 50%", "50% of", "of the", "the proteins", "proteins in", "the swiss", "swiss prot", "prot database", "database at", "at the", "the time", "time were", "were n", "n glycosylated", "apweiler et", "al. 1999", "1999 .", ". it", "it is", "is now", "now established", "established that", "that the", "the majority", "majority of", "the secretory", "secretory pathway", "pathway require", "require glycosylation", "glycosylation in", "in order", "order to", "to achieve", "achieve proper", "proper folding.
              the", "folding.
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              all", "cell.
              all n", "linked glycans", "are derived", "derived from", "from a", "a common", "common 14", "14 sugar", "sugar oligosaccharide", "oligosaccharide synthesized", "synthesized in", "which is", "is attached", "attached co", "co translationally", "translationally to", "protein while", "while this", "this is", "is being", "being translated", "translated inside", "the reticulum.", "reticulum. the", "the process", "the synthesis", "synthesis of", "of this", "this glycan", "known as", "as synthesis", "the n", "glycan precursor", "precursor or", "or llo", "constitutes one", "one of", "most conserved", "conserved pathways", "pathways in", "in eukaryotes", "and has", "has been", "been also", "also observed", "observed in", "in some", "some eubacteria.", "eubacteria. the", "the attachment", "attachment usually", "usually happens", "happens on", "on an", "an asparagine", "asparagine residue", "residue within", "within the", "the consensus", "consensus sequence", "sequence asparagine", "asparagine x", "x threonine", "threonine by", "by an", "an complex", "complex called", "called oligosaccharyl", "oligosaccharyl transferase", "ost .
              after", ".
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              once", "modification.
              once the", "the glycoprotein", "glycoprotein has", "has achieved", "achieved proper", "is transported", "transported via", "via the", "the cis", "cis golgi", "golgi through", "through all", "all the", "golgi compartments", "is further", "further modified", "modified according", "according to", "the glycoprotein.", "glycoprotein. this", "this process", "process involves", "involves relatively", "relatively few", "few enzymes", "enzymes but", "but due", "due to", "to its", "its combinatorial", "combinatorial nature", "can lead", "lead to", "to several", "several millions", "millions of", "of different", "different possible", "possible modifications.", "modifications. the", "the exact", "exact topography", "topography of", "this network", "network of", "of reactions", "reactions has", "has not", "not been", "been established", "established yet", "representing one", "the major", "major challenges", "challenges after", "after the", "the sequencing", "sequencing of", "the human", "human genome", "hossler et", "al. 2006", "2006 .
              since", ".
              since n", "n glycosylation", "is involved", "in an", "an great", "great number", "number of", "different processes", "from cell", "cell cell", "cell interaction", "interaction to", "to folding", "folding control", "mutations in", "in one", "the genes", "genes involved", "in glycan", "glycan assembly", "assembly and/or", "and/or modification", "modification can", "to severe", "severe development", "development problems", "often affecting", "affecting the", "the central", "central nervous", "nervous system", "system .", ". all", "the diseases", "diseases in", "in genes", "in glycosylation", "glycosylation are", "are collectively", "collectively known", "as congenital", "congenital disorders", "disorders of", "of glycosylation", "sparks et", "al. 2003", "and classified", "classified as", "as cdg", "cdg type", "type i", "i for", "for the", "genes in", "the llo", "llo synthesis", "synthesis pathway", "and cdg", "type ii", "ii for", "the others.", "linked glycosylation is", "glycosylation is the", "is the most", "the most important", "most important form", "important form of", "form of post", "of post translational", "post translational modification", "translational modification for", "modification for proteins", "for proteins synthesized", "proteins synthesized and", "synthesized and folded", "and folded in", "folded in the", "in the endoplasmic", "the endoplasmic reticulum", "reticulum stanley", "stanley et al.", "et al. 2009", "al. 2009 .", "2009 . an", ". an early", "an early study", "early study in", "study in 1999", "in 1999 revealed", "1999 revealed that", "revealed that about", "that about 50%", "about 50% of", "50% of the", "of the proteins", "the proteins in", "proteins in the", "in the swiss", "the swiss prot", "swiss prot database", "prot database at", "database at the", "at the time", "the time were", "time were n", "were n glycosylated", "glycosylated apweiler", "apweiler et al.", "et al. 1999", "al. 1999 .", "1999 . it", ". it is", "it is now", "is now established", "now established that", "established that the", "that the majority", "the majority of", "majority of the", "in the secretory", "the secretory pathway", "secretory pathway require", "pathway require glycosylation", "require glycosylation in", "glycosylation in order", "in order to", "order to achieve", "to achieve proper", "achieve proper folding.
              the", "proper folding.
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              all", "the cell.
              all n", "cell.
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              after being", ".
              after being attached", "being attached to", "attached to an", "to an unfolded", "an unfolded protein", "protein the", "the glycan is", "glycan is used", "is used as", "used as a", "as a label", "a label molecule", "label molecule in", "molecule in the", "in the folding", "the folding process", "process also", "also known as", "known as calnexin/calreticulin", "as calnexin/calreticulin cycle", "lederkremer 2009 .", "2009 . the", ". the majority", "of the glycoproteins", "the glycoproteins in", "glycoproteins in the", "the er require", "er require at", "require at least", "at least one", "least one glycosylated", "one glycosylated residue", "glycosylated residue in", "residue in order", "achieve proper folding", "folding even", "even if it", "if it has", "it has been", "has been shown", "been shown that", "shown that a", "that a smaller", "a smaller portion", "smaller portion of", "portion of the", "the er can", "er can be", "can be folded", "be folded without", "folded without this", "without this modification.
              once", "this modification.
              once the", "modification.
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              since", "2006 .
              since n", ".
              since n glycosylation", "n glycosylation is", "glycosylation is involved", "is involved in", "involved in an", "in an great", "an great number", "great number of", "number of different", "of different processes", "processes from", "from cell cell", "cell cell interaction", "cell interaction to", "interaction to folding", "to folding control", "control mutations", "mutations in one", "in one of", "of the genes", "the genes involved", "genes involved in", "involved in glycan", "in glycan assembly", "glycan assembly and/or", "assembly and/or modification", "and/or modification can", "modification can lead", "lead to severe", "to severe development", "severe development problems", "problems often", "often affecting the", "affecting the central", "the central nervous", "central nervous system", "nervous system .", "system . all", ". all the", "all the diseases", "the diseases in", "diseases in genes", "in genes involved", "involved in glycosylation", "in glycosylation are", "glycosylation are collectively", "are collectively known", "collectively known as", "known as congenital", "as congenital disorders", "congenital disorders of", "disorders of glycosylation", "glycosylation cdg", "sparks et al.", "et al. 2003", "and classified as", "classified as cdg", "as cdg type", "cdg type i", "type i for", "i for the", "for the genes", "the genes in", "genes in the", "in the llo", "the llo synthesis", "llo synthesis pathway", "pathway and", "and cdg type", "cdg type ii", "type ii for", "ii for the", "for the others.", "n linked glycosylation is", "linked glycosylation is the", "glycosylation is the most", "is the most important", "the most important form", "most important form of", "important form of post", "form of post translational", "of post translational modification", "post translational modification for", "translational modification for proteins", "modification for proteins synthesized", "for proteins synthesized and", "proteins synthesized and folded", "synthesized and folded in", "and folded in the", "folded in the endoplasmic", "in the endoplasmic reticulum", "endoplasmic reticulum stanley", "reticulum stanley et", "stanley et al. 2009", "et al. 2009 .", "al. 2009 . an", "2009 . an early", ". an early study", "an early study in", "early study in 1999", "study in 1999 revealed", "in 1999 revealed that", "1999 revealed that about", "revealed that about 50%", "that about 50% of", "about 50% of the", "50% of the proteins", "of the proteins in", "the proteins in the", "proteins in the swiss", "in the swiss prot", "the swiss prot database", "swiss prot database at", "prot database at the", "database at the time", "at the time were", "the time were n", "time were n glycosylated", "n glycosylated apweiler", "glycosylated apweiler et", "apweiler et al. 1999", "et al. 1999 .", "al. 1999 . it", "1999 . it is", ". it is now", "it is now established", "is now established that", "now established that the", "established that the majority", "that the majority of", "the majority of the", "majority of the proteins", "proteins in the secretory", "in the secretory pathway", "the secretory pathway require", "secretory pathway require glycosylation", "pathway require glycosylation in", "require glycosylation in order", "glycosylation in order to", "in order to achieve", "order to achieve proper", "to achieve proper folding.
              the", "achieve proper folding.
              the addition", "proper folding.
              the addition of", "folding.
              the addition of an", "addition of an n", "of an n glycan", "an n glycan to", "n glycan to a", "glycan to a protein", "to a protein can", "a protein can have", "protein can have several", "can have several roles", "several roles shental", "roles shental bechor", "shental bechor & levy", "bechor & levy 2009", "& levy 2009 .", "levy 2009 . first", ". first glycans", "first glycans enhance", "glycans enhance the solubility", "enhance the solubility and", "the solubility and stability", "solubility and stability of", "and stability of the", "stability of the proteins", "proteins in the er", "the er the", "er the golgi", "the golgi and on", "golgi and on the", "and on the outside", "on the outside of", "the outside of the", "outside of the cell", "of the cell membrane", "cell membrane where", "membrane where the", "where the composition of", "the composition of the", "composition of the medium", "of the medium is", "the medium is strongly", "medium is strongly hydrophilic", "is strongly hydrophilic and", "strongly hydrophilic and where", "hydrophilic and where proteins", "where proteins that", "proteins that are", "that are mostly hydrophobic", "mostly hydrophobic have", "hydrophobic have difficulty", "have difficulty folding properly.", "difficulty folding properly. second", "properly. second n", "second n glycans", "n glycans are used", "glycans are used as", "are used as signal", "used as signal molecules", "as signal molecules during", "signal molecules during the", "molecules during the folding", "during the folding and", "the folding and transport", "folding and transport process", "and transport process of", "transport process of the", "process of the protein:", "of the protein: they", "the protein: they have", "protein: they have the", "they have the role", "have the role of", "the role of labels", "role of labels to", "of labels to determine", "labels to determine when", "to determine when a", "determine when a protein", "when a protein must", "a protein must interact", "protein must interact with", "must interact with a", "interact with a chaperon", "a chaperon be", "chaperon be transported", "be transported to the", "transported to the golgi", "the golgi or", "golgi or targeted", "or targeted for degradation", "targeted for degradation in", "for degradation in case", "degradation in case of", "in case of major", "case of major folding", "of major folding defects.", "major folding defects. third", "defects. third and", "third and most", "most importantly n", "importantly n glycans", "n glycans on completely", "glycans on completely folded", "on completely folded proteins", "completely folded proteins are", "folded proteins are involved", "proteins are involved in", "are involved in a", "involved in a wide", "in a wide range", "a wide range of", "wide range of processes:", "range of processes: they", "of processes: they help", "processes: they help determine", "they help determine the", "help determine the specificity", "determine the specificity of", "the specificity of membrane", "specificity of membrane receptors", "of membrane receptors in", "membrane receptors in innate", "receptors in innate immunity", "in innate immunity or", "innate immunity or in", "immunity or in cell", "or in cell to", "in cell to cell", "cell to cell interactions", "cell interactions they", "interactions they can", "they can change the", "can change the properties", "change the properties of", "the properties of hormones", "properties of hormones and", "of hormones and secreted", "hormones and secreted proteins", "secreted proteins or", "proteins or of", "or of the proteins", "proteins in the vesicular", "in the vesicular system", "the vesicular system inside", "vesicular system inside the", "system inside the cell.
              all", "inside the cell.
              all n", "the cell.
              all n linked", "cell.
              all n linked glycans", "n linked glycans are", "linked glycans are derived", "glycans are derived from", "are derived from a", "derived from a common", "from a common 14", "a common 14 sugar", "common 14 sugar oligosaccharide", "14 sugar oligosaccharide synthesized", "sugar oligosaccharide synthesized in", "oligosaccharide synthesized in the", "synthesized in the er", "the er which", "er which is", "which is attached co", "is attached co translationally", "attached co translationally to", "co translationally to a", "translationally to a protein", "to a protein while", "a protein while this", "protein while this is", "while this is being", "this is being translated", "is being translated inside", "being translated inside the", "translated inside the reticulum.", "inside the reticulum. the", "the reticulum. the process", "reticulum. the process of", "the process of the", "process of the synthesis", "of the synthesis of", "the synthesis of this", "synthesis of this glycan", "this glycan known", "glycan known as", "known as synthesis of", "as synthesis of the", "synthesis of the n", "of the n glycan", "the n glycan precursor", "n glycan precursor or", "glycan precursor or llo", "or llo constitutes", "llo constitutes one", "constitutes one of the", "one of the most", "of the most conserved", "the most conserved pathways", "most conserved pathways in", "conserved pathways in eukaryotes", "in eukaryotes and", "eukaryotes and has", "and has been also", "has been also observed", "been also observed in", "also observed in some", "observed in some eubacteria.", "in some eubacteria. the", "some eubacteria. the attachment", "eubacteria. the attachment usually", "the attachment usually happens", "attachment usually happens on", "usually happens on an", "happens on an asparagine", "on an asparagine residue", "an asparagine residue within", "asparagine residue within the", "residue within the consensus", "within the consensus sequence", "the consensus sequence asparagine", "consensus sequence asparagine x", "sequence asparagine x threonine", "asparagine x threonine by", "x threonine by an", "threonine by an complex", "by an complex called", "an complex called oligosaccharyl", "complex called oligosaccharyl transferase", "oligosaccharyl transferase ost", "transferase ost .
              after", "ost .
              after being attached", ".
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              once", "without this modification.
              once the", "this modification.
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              since", "al. 2006 .
              since n", "2006 .
              since n glycosylation", ".
              since n glycosylation is", "n glycosylation is involved", "glycosylation is involved in", "is involved in an", "involved in an great", "in an great number", "an great number of", "great number of different", "number of different processes", "different processes from", "processes from cell", "from cell cell interaction", "cell cell interaction to", "cell interaction to folding", "interaction to folding control", "folding control mutations", "control mutations in", "mutations in one of", "in one of the", "one of the genes", "of the genes involved", "the genes involved in", "genes involved in glycan", "involved in glycan assembly", "in glycan assembly and/or", "glycan assembly and/or modification", "assembly and/or modification can", "and/or modification can lead", "modification can lead to", "can lead to severe", "lead to severe development", "to severe development problems", "development problems often", "problems often affecting", "often affecting the central", "affecting the central nervous", "the central nervous system", "central nervous system .", "nervous system . all", "system . all the", ". all the diseases", "all the diseases in", "the diseases in genes", "diseases in genes involved", "in genes involved in", "genes involved in glycosylation", "involved in glycosylation are", "in glycosylation are collectively", "glycosylation are collectively known", "are collectively known as", "collectively known as congenital", "known as congenital disorders", "as congenital disorders of", "congenital disorders of glycosylation", "of glycosylation cdg", "cdg sparks", "sparks et al. 2003", "2003 and", "and classified as cdg", "classified as cdg type", "as cdg type i", "cdg type i for", "type i for the", "i for the genes", "for the genes in", "the genes in the", "genes in the llo", "in the llo synthesis", "the llo synthesis pathway", "synthesis pathway and", "pathway and cdg", "and cdg type ii", "cdg type ii for", "type ii for the", "ii for the others.", "n linked glycosylation is the", "linked glycosylation is the most", "glycosylation is the most important", "is the most important form", "the most important form of", "most important form of post", "important form of post translational", "form of post translational modification", "of post translational modification for", "post translational modification for proteins", "translational modification for proteins synthesized", "modification for proteins synthesized and", "for proteins synthesized and folded", "proteins synthesized and folded in", "synthesized and folded in the", "and folded in the endoplasmic", "folded in the endoplasmic reticulum", "the endoplasmic reticulum stanley", "endoplasmic reticulum stanley et", "reticulum stanley et al.", "stanley et al. 2009 .", "et al. 2009 . an", "al. 2009 . an early", "2009 . an early study", ". an early study in", "an early study in 1999", "early study in 1999 revealed", "study in 1999 revealed that", "in 1999 revealed that about", "1999 revealed that about 50%", "revealed that about 50% of", "that about 50% of the", "about 50% of the proteins", "50% of the proteins in", "of the proteins in the", "the proteins in the swiss", "proteins in the swiss prot", "in the swiss prot database", "the swiss prot database at", "swiss prot database at the", "prot database at the time", "database at the time were", "at the time were n", "the time were n glycosylated", "were n glycosylated apweiler", "n glycosylated apweiler et", "glycosylated apweiler et al.", "apweiler et al. 1999 .", "et al. 1999 . it", "al. 1999 . it is", "1999 . it is now", ". it is now established", "it is now established that", "is now established that the", "now established that the majority", "established that the majority of", "that the majority of the", "the majority of the proteins", "majority of the proteins in", "the proteins in the secretory", "proteins in the secretory pathway", "in the secretory pathway require", "the secretory pathway require glycosylation", "secretory pathway require glycosylation in", "pathway require glycosylation in order", "require glycosylation in order to", "glycosylation in order to achieve", "in order to achieve proper", "order to achieve proper folding.
              the", "to achieve proper folding.
              the addition", "achieve proper folding.
              the addition of", "proper folding.
              the addition of an", "folding.
              the addition of an n", "addition of an n glycan", "of an n glycan to", "an n glycan to a", "n glycan to a protein", "glycan to a protein can", "to a protein can have", "a protein can have several", "protein can have several roles", "have several roles shental", "several roles shental bechor", "roles shental bechor &", "shental bechor & levy 2009", "bechor & levy 2009 .", "& levy 2009 . first", "2009 . first glycans", ". first glycans enhance", "first glycans enhance the", "glycans enhance the solubility and", "enhance the solubility and stability", "the solubility and stability of", "solubility and stability of the", "and stability of the proteins", "stability of the proteins in", "the proteins in the er", "in the er the", "the er the golgi", "er the golgi and", "the golgi and on the", "golgi and on the outside", "and on the outside of", "on the outside of the", "the outside of the cell", "outside of the cell membrane", "the cell membrane where", "cell membrane where the", "membrane where the composition", "where the composition of the", "the composition of the medium", "composition of the medium is", "of the medium is strongly", "the medium is strongly hydrophilic", "medium is strongly hydrophilic and", "is strongly hydrophilic and where", "strongly hydrophilic and where proteins", "and where proteins that", "where proteins that are", "proteins that are mostly", "are mostly hydrophobic have", "mostly hydrophobic have difficulty", "hydrophobic have difficulty folding", "have difficulty folding properly. second", "folding properly. second n", "properly. second n glycans", "second n glycans are", "n glycans are used as", "glycans are used as signal", "are used as signal molecules", "used as signal molecules during", "as signal molecules during the", "signal molecules during the folding", "molecules during the folding and", "during the folding and transport", "the folding and transport process", "folding and transport process of", "and transport process of the", "transport process of the protein:", "process of the protein: they", "of the protein: they have", "the protein: they have the", "protein: they have the role", "they have the role of", "have the role of labels", "the role of labels to", "role of labels to determine", "of labels to determine when", "labels to determine when a", "to determine when a protein", "determine when a protein must", "when a protein must interact", "a protein must interact with", "protein must interact with a", "must interact with a chaperon", "with a chaperon be", "a chaperon be transported", "chaperon be transported to", "be transported to the golgi", "to the golgi or", "the golgi or targeted", "golgi or targeted for", "or targeted for degradation in", "targeted for degradation in case", "for degradation in case of", "degradation in case of major", "in case of major folding", "case of major folding defects.", "of major folding defects. third", "folding defects. third and", "defects. third and most", "third and most importantly", "and most importantly n", "most importantly n glycans", "importantly n glycans on", "n glycans on completely folded", "glycans on completely folded proteins", "on completely folded proteins are", "completely folded proteins are involved", "folded proteins are involved in", "proteins are involved in a", "are involved in a wide", "involved in a wide range", "in a wide range of", "a wide range of processes:", "wide range of processes: they", "range of processes: they help", "of processes: they help determine", "processes: they help determine the", "they help determine the specificity", "help determine the specificity of", "determine the specificity of membrane", "the specificity of membrane receptors", "specificity of membrane receptors in", "of membrane receptors in innate", "membrane receptors in innate immunity", "receptors in innate immunity or", "in innate immunity or in", "innate immunity or in cell", "immunity or in cell to", "or in cell to cell", "in cell to cell interactions", "to cell interactions they", "cell interactions they can", "interactions they can change", "they can change the properties", "can change the properties of", "change the properties of hormones", "the properties of hormones and", "properties of hormones and secreted", "of hormones and secreted proteins", "and secreted proteins or", "secreted proteins or of", "proteins or of the", "or of the proteins in", "the proteins in the vesicular", "proteins in the vesicular system", "in the vesicular system inside", "the vesicular system inside the", "vesicular system inside the cell.
              all", "system inside the cell.
              all n", "inside the cell.
              all n linked", "the cell.
              all n linked glycans", "cell.
              all n linked glycans are", "n linked glycans are derived", "linked glycans are derived from", "glycans are derived from a", "are derived from a common", "derived from a common 14", "from a common 14 sugar", "a common 14 sugar oligosaccharide", "common 14 sugar oligosaccharide synthesized", "14 sugar oligosaccharide synthesized in", "sugar oligosaccharide synthesized in the", "oligosaccharide synthesized in the er", "in the er which", "the er which is", "er which is attached", "which is attached co translationally", "is attached co translationally to", "attached co translationally to a", "co translationally to a protein", "translationally to a protein while", "to a protein while this", "a protein while this is", "protein while this is being", "while this is being translated", "this is being translated inside", "is being translated inside the", "being translated inside the reticulum.", "translated inside the reticulum. the", "inside the reticulum. the process", "the reticulum. the process of", "reticulum. the process of the", "the process of the synthesis", "process of the synthesis of", "of the synthesis of this", "the synthesis of this glycan", "of this glycan known", "this glycan known as", "glycan known as synthesis", "known as synthesis of the", "as synthesis of the n", "synthesis of the n glycan", "of the n glycan precursor", "the n glycan precursor or", "n glycan precursor or llo", "precursor or llo constitutes", "or llo constitutes one", "llo constitutes one of", "constitutes one of the most", "one of the most conserved", "of the most conserved pathways", "the most conserved pathways in", "most conserved pathways in eukaryotes", "pathways in eukaryotes and", "in eukaryotes and has", "eukaryotes and has been", "and has been also observed", "has been also observed in", "been also observed in some", "also observed in some eubacteria.", "observed in some eubacteria. the", "in some eubacteria. the attachment", "some eubacteria. the attachment usually", "eubacteria. the attachment usually happens", "the attachment usually happens on", "attachment usually happens on an", "usually happens on an asparagine", "happens on an asparagine residue", "on an asparagine residue within", "an asparagine residue within the", "asparagine residue within the consensus", "residue within the consensus sequence", "within the consensus sequence asparagine", "the consensus sequence asparagine x", "consensus sequence asparagine x threonine", "sequence asparagine x threonine by", "asparagine x threonine by an", "x threonine by an complex", "threonine by an complex called", "by an complex called oligosaccharyl", "an complex called oligosaccharyl transferase", "called oligosaccharyl transferase ost", "oligosaccharyl transferase ost .
              after", "transferase ost .
              after being", "ost .
              after being attached to", ".
              after being attached to an", "being attached to an unfolded", "attached to an unfolded protein", "an unfolded protein the", "unfolded protein the glycan", "protein the glycan is", "the glycan is used as", "glycan is used as a", "is used as a label", "used as a label molecule", "as a label molecule in", "a label molecule in the", "label molecule in the folding", "molecule in the folding process", "the folding process also", "folding process also known", "process also known as", "also known as calnexin/calreticulin cycle", "calnexin/calreticulin cycle lederkremer", "cycle lederkremer 2009", "lederkremer 2009 . the majority", "2009 . the majority of", ". the majority of the", "the majority of the glycoproteins", "majority of the glycoproteins in", "of the glycoproteins in the", "the glycoproteins in the er", "glycoproteins in the er require", "in the er require at", "the er require at least", "er require at least one", "require at least one glycosylated", "at least one glycosylated residue", "least one glycosylated residue in", "one glycosylated residue in order", "glycosylated residue in order to", "residue in order to achieve", "order to achieve proper folding", "achieve proper folding even", "proper folding even if", "folding even if it", "even if it has been", "if it has been shown", "it has been shown that", "has been shown that a", "been shown that a smaller", "shown that a smaller portion", "that a smaller portion of", "a smaller portion of the", "smaller portion of the proteins", "portion of the proteins in", "proteins in the er can", "in the er can be", "the er can be folded", "er can be folded without", "can be folded without this", "be folded without this modification.
              once", "folded without this modification.
              once the", "without this modification.
              once the glycoprotein", "this modification.
              once the glycoprotein has", "modification.
              once the glycoprotein has achieved", "the glycoprotein has achieved proper", "glycoprotein has achieved proper folding", "achieved proper folding it", "proper folding it is", "folding it is transported", "it is transported via the", "is transported via the cis", "transported via the cis golgi", "via the cis golgi through", "the cis golgi through all", "cis golgi through all the", "golgi through all the golgi", "through all the golgi compartments", "the golgi compartments where", "golgi compartments where the", "compartments where the glycan", "where the glycan is further", "the glycan is further modified", "glycan is further modified according", "is further modified according to", "further modified according to the", "modified according to the properties", "according to the properties of", "to the properties of the", "the properties of the glycoprotein.", "properties of the glycoprotein. this", "of the glycoprotein. this process", "the glycoprotein. this process involves", "glycoprotein. this process involves relatively", "this process involves relatively few", "process involves relatively few enzymes", "involves relatively few enzymes but", "relatively few enzymes but due", "few enzymes but due to", "enzymes but due to its", "but due to its combinatorial", "due to its combinatorial nature", "its combinatorial nature can", "combinatorial nature can lead", "nature can lead to", "can lead to several millions", "lead to several millions of", "to several millions of different", "several millions of different possible", "millions of different possible modifications.", "of different possible modifications. the", "different possible modifications. the exact", "possible modifications. the exact topography", "modifications. the exact topography of", "the exact topography of this", "exact topography of this network", "topography of this network of", "of this network of reactions", "this network of reactions has", "network of reactions has not", "of reactions has not been", "reactions has not been established", "has not been established yet", "been established yet representing", "established yet representing one", "yet representing one of", "representing one of the major", "one of the major challenges", "of the major challenges after", "the major challenges after the", "major challenges after the sequencing", "challenges after the sequencing of", "after the sequencing of the", "the sequencing of the human", "sequencing of the human genome", "the human genome hossler", "human genome hossler et", "genome hossler et al.", "hossler et al. 2006 .
              since", "et al. 2006 .
              since n", "al. 2006 .
              since n glycosylation", "2006 .
              since n glycosylation is", ".
              since n glycosylation is involved", "n glycosylation is involved in", "glycosylation is involved in an", "is involved in an great", "involved in an great number", "in an great number of", "an great number of different", "great number of different processes", "of different processes from", "different processes from cell", "processes from cell cell", "from cell cell interaction to", "cell cell interaction to folding", "cell interaction to folding control", "to folding control mutations", "folding control mutations in", "control mutations in one", "mutations in one of the", "in one of the genes", "one of the genes involved", "of the genes involved in", "the genes involved in glycan", "genes involved in glycan assembly", "involved in glycan assembly and/or", "in glycan assembly and/or modification", "glycan assembly and/or modification can", "assembly and/or modification can lead", "and/or modification can lead to", "modification can lead to severe", "can lead to severe development", "lead to severe development problems", "severe development problems often", "development problems often affecting", "problems often affecting the", "often affecting the central nervous", "affecting the central nervous system", "the central nervous system .", "central nervous system . all", "nervous system . all the", "system . all the diseases", ". all the diseases in", "all the diseases in genes", "the diseases in genes involved", "diseases in genes involved in", "in genes involved in glycosylation", "genes involved in glycosylation are", "involved in glycosylation are collectively", "in glycosylation are collectively known", "glycosylation are collectively known as", "are collectively known as congenital", "collectively known as congenital disorders", "known as congenital disorders of", "as congenital disorders of glycosylation", "disorders of glycosylation cdg", "cdg sparks et", "al. 2003 and", "2003 and classified", "and classified as cdg type", "classified as cdg type i", "as cdg type i for", "cdg type i for the", "type i for the genes", "i for the genes in", "for the genes in the", "the genes in the llo", "genes in the llo synthesis", "in the llo synthesis pathway", "llo synthesis pathway and", "synthesis pathway and cdg", "pathway and cdg type", "and cdg type ii for", "cdg type ii for the", "type ii for the others." ] }, { "record_id": "GLY_000594_1_1382", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "446343", "r hsa", "hsa 446343", "r hsa 446343" ] }, { "record_id": "GLY_000594_1_1382", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "localization of", "of the", "the pinch", "pinch ilk", "ilk parvin", "parvin complex", "complex to", "to focal", "focal adhesions", "localization of the", "of the pinch", "the pinch ilk", "pinch ilk parvin", "ilk parvin complex", "parvin complex to", "complex to focal", "to focal adhesions", "localization of the pinch", 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              this pathway has", "forward direction.

              this pathway has been", "direction.

              this pathway has been most", "pathway has been most extensively", "has been most extensively analyzed", "been most extensively analyzed at", "most extensively analyzed at the", "extensively analyzed at the genetic", "analyzed at the genetic and", "at the genetic and biochemical", "the genetic and biochemical level", "genetic and biochemical level in", "and biochemical level in hamster", "biochemical level in hamster cell", "level in hamster cell lines.", "in hamster cell lines. all", "hamster cell lines. all three", "cell lines. all three enzymes", "lines. all three enzymes have", "all three enzymes have also", "three enzymes have also been", "enzymes have also been purified", "have also been purified from", "also been purified from human", "been purified from human sources", "from human sources however", "sources however and", "however and the key", "and the key features of", "the key features of these", "key features of these reactions", "features of these reactions have", "of these reactions have been", "these reactions have been confirmed", "reactions have been confirmed from", "have been confirmed from studies", "been confirmed from studies of", "confirmed from studies of this", "from studies of this human", "studies of this human material", "this human material jones", "human material jones 1980", "jones 1980 webster et", "1980 webster et al.", "webster et al. 2001 .

              all", "et al. 2001 .

              all other", "al. 2001 .

              all other pyrimidines", "2001 .

              all other pyrimidines are", ".

              all other pyrimidines are synthesized", "other pyrimidines are synthesized from", "pyrimidines are synthesized from ump.", "are synthesized from ump. the", "synthesized from ump. the reactions", "from ump. the reactions annotaed", "ump. the reactions annotaed here", "reactions annotaed here catalyzed", "annotaed here catalyzed by", "here catalyzed by dcmp", "catalyzed by dcmp deaminase and", "by dcmp deaminase and dutp", "dcmp deaminase and dutp diphosphatase", "deaminase and dutp diphosphatase yield", "and dutp diphosphatase yield dump", "diphosphatase yield dump which", "yield dump which in", "dump which in turn", "which in turn is converted", "in turn is converted to", "turn is converted to tmp", "is converted to tmp by", "converted to tmp by thymidylate", "to tmp by thymidylate synthase." ] }, { "record_id": "GLY_000594_1_1390", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5083625", "r hsa", "hsa 5083625", "r hsa 5083625" ] }, { "record_id": "GLY_000594_1_1390", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective galnt3", "galnt3 causes", "causes hftc", "defective galnt3 causes", "galnt3 causes hftc", "defective galnt3 causes hftc", "the family", "family of", "of udp", "udp galnac:polypeptide", "galnac:polypeptide n", "n acetylgalactosaminyltransferases", "galnac transferases", "carry out", "out the", "the addition", "addition of", "of n", "n acetylgalactosamine", "on serine", "threonine or", "or possibly", "possibly tyrosine", "tyrosine residues", "residues on", "on a", "a wide", "wide variety", "variety of", "of proteins", "most commonly", "commonly associated", "associated with", "with mucins.", "this is", "is the", "the initial", "initial reaction", "reaction in", "in the", "the biosynthesis", "biosynthesis of", "of galnac", "galnac type", "type o", "o linked", "linked oligosaccharides", "wandall et", "et al.", "al. 1997", "1997 .", ". this", "this reaction", "reaction takes", "takes place", "place in", "the golgi", "golgi apparatus", "rottger et", "al. 1998", "1998 .", ". there", "there are", "are 20", "20 known", "known members", "members of", "of the", "the galnt", "galnt family", "15 of", "of which", "which have", "have been", "been characterised", "characterised and", "and 5", "5 candidate", "candidate members", "members which", "which are", "are thought", "thought to", "to belong", "belong to", "to this", "this family", "family based", "based on", "on sequence", "sequence similarity", "bennett et", "al. 2012", "2012 .", ". the", "family is", "is classified", "classified as", "as belonging", "belonging to", "to cazy", "cazy family", "family gt27.", "gt27. defects", "defects in", "in one", "one of", "family genes", "can cause", "cause familial", "familial hyperphosphatemic", "hyperphosphatemic tumoral", "tumoral calcinosis", "mim:211900 .", "211900 .", ". hftc", "hftc is", "is a", "a rare", "rare autosomal", "autosomal recessive", "recessive severe", "severe metabolic", "metabolic disorder", "disorder characterised", "characterised by", "by the", "the progressive", "progressive deposition", "deposition of", "of calcium", "calcium phosphate", "phosphate crystals", "crystals in", "the skin", "soft tissues", "tissues and", "and sometimes", "sometimes bone", "chefetz et", "al. 2005", "2005 .", "the biochemical", "biochemical observation", "observation is", "is hyperphosphatemia", "caused by", "by increased", "increased renal", "renal absorption", "absorption of", "of phosphate", "ichikawa et", ". some", "some patients", "patients manifest", "manifest recurrent", "painful swellings", "swellings of", "the long", "long bones", "bones with", "with radiological", "radiological evidence", "evidence of", "of periosteal", "periosteal reaction", "reaction and", "and cortical", "cortical hyperostosis", "frishberg et", "the family of", "family of udp", "of udp galnac:polypeptide", "udp galnac:polypeptide n", "galnac:polypeptide n acetylgalactosaminyltransferases", "acetylgalactosaminyltransferases galnac", "transferases galnts", "galnts carry", "carry out the", "out the addition", "the addition of", "addition of n", "of n acetylgalactosamine", "acetylgalactosamine galnac", "galnac on", "serine threonine", "threonine or possibly", "or possibly tyrosine", "possibly tyrosine residues", "tyrosine residues on", "residues on a", "on a wide", "a wide variety", "wide variety of", "variety of proteins", "proteins most", "most commonly associated", "commonly associated with", "associated with mucins.", "mucins. this", "this is the", "is the initial", "the initial reaction", "initial reaction in", "reaction in the", "in the biosynthesis", "the biosynthesis of", "biosynthesis of galnac", "of galnac type", "galnac type o", "type o linked", "o linked oligosaccharides", "oligosaccharides wandall", "wandall et al.", "et al. 1997", "al. 1997 .", "1997 . this", ". this reaction", "this reaction takes", "reaction takes place", "takes place in", "place in the", "in the golgi", "the golgi apparatus", "apparatus rottger", "rottger et al.", "et al. 1998", "al. 1998 .", "1998 . there", ". there are", "there are 20", "are 20 known", "20 known members", "known members of", "members of the", "of the galnt", "the galnt family", "family 15", "15 of which", "of which have", "which have been", "have been characterised", "been characterised and", "characterised and 5", "and 5 candidate", "5 candidate members", "candidate members which", "members which are", "which are thought", "are thought to", "thought to belong", "to belong to", "belong to this", "to this family", "this family based", "family based on", "based on sequence", "on sequence similarity", "similarity bennett", "bennett et al.", "et al. 2012", "al. 2012 .", "2012 . the", ". the galnt", "galnt family is", "family is classified", "is classified as", "classified as belonging", "as belonging to", "belonging to cazy", "to cazy family", "cazy family gt27.", "family gt27. defects", "gt27. defects in", "defects in one", "in one of", "one of the", "galnt family genes", "genes galnt3", "galnt3 mim:601756", "can cause familial", "cause familial hyperphosphatemic", "familial hyperphosphatemic tumoral", "hyperphosphatemic tumoral calcinosis", "calcinosis hftc", "hftc mim:211900", "mim:211900 . hftc", "211900 . hftc", ". hftc is", "hftc is a", "is a rare", "a rare autosomal", "rare autosomal recessive", "autosomal recessive severe", "recessive severe metabolic", "severe metabolic disorder", "metabolic disorder characterised", "disorder characterised by", "characterised by the", "by the progressive", "the progressive deposition", "progressive deposition of", "deposition of calcium", "of calcium phosphate", "calcium phosphate crystals", "phosphate crystals in", "crystals in the", "in the skin", "skin soft", "soft tissues and", "tissues and sometimes", "and sometimes bone", "bone chefetz", "chefetz et al.", "et al. 2005", "al. 2005 .", "2005 . the", ". the biochemical", "the biochemical observation", "biochemical observation is", "observation is hyperphosphatemia", "hyperphosphatemia caused", "caused by increased", "by increased renal", "increased renal absorption", "renal absorption of", "absorption of phosphate", "phosphate chefetz", "2005 ichikawa", "ichikawa et al.", "2005 . some", ". some patients", "some patients manifest", "patients manifest recurrent", "recurrent transient", "transient painful", "painful swellings of", "swellings of the", "of the long", "the long bones", "long bones with", "bones with radiological", "with radiological evidence", "radiological evidence of", "evidence of periosteal", "of periosteal reaction", "periosteal reaction and", "reaction and cortical", "and cortical hyperostosis", "hyperostosis frishberg", "frishberg et al.", "the family of udp", "family of udp galnac:polypeptide", "of udp galnac:polypeptide n", "udp galnac:polypeptide n acetylgalactosaminyltransferases", "n acetylgalactosaminyltransferases galnac", "acetylgalactosaminyltransferases galnac transferases", "galnac transferases galnts", "galnts carry out", "carry out the addition", "out the addition of", "the addition of n", "addition of n acetylgalactosamine", "n acetylgalactosamine galnac", "galnac on serine", "on serine threonine", "serine threonine or", "threonine or possibly tyrosine", "or possibly tyrosine residues", "possibly tyrosine residues on", "tyrosine residues on a", "residues on a wide", "on a wide variety", "a wide variety of", "wide variety of proteins", "of proteins most", "proteins most commonly", "most commonly associated with", "commonly associated with mucins.", "with mucins. this", "mucins. this is", "this is the initial", "is the initial reaction", "the initial reaction in", "initial reaction in the", "reaction in the biosynthesis", "in the biosynthesis of", "the biosynthesis of galnac", "biosynthesis of galnac type", "of galnac type o", "galnac type o linked", "type o linked oligosaccharides", "linked oligosaccharides wandall", "oligosaccharides wandall et", "wandall et al. 1997", "et al. 1997 .", "al. 1997 . this", "1997 . this reaction", ". this reaction takes", "this reaction takes place", "reaction takes place in", "takes place in the", "place in the golgi", "in the golgi apparatus", "golgi apparatus rottger", "apparatus rottger et", "rottger et al. 1998", "et al. 1998 .", "al. 1998 . there", "1998 . there are", ". there are 20", "there are 20 known", "are 20 known members", "20 known members of", "known members of the", "members of the galnt", "of the galnt family", "galnt family 15", "family 15 of", "15 of which have", "of which have been", "which have been characterised", "have been characterised and", "been characterised and 5", "characterised and 5 candidate", "and 5 candidate members", "5 candidate members which", "candidate members which are", "members which are thought", "which are thought to", "are thought to belong", "thought to belong to", "to belong to this", "belong to this family", "to this family based", "this family based on", "family based on sequence", "based on sequence similarity", "sequence similarity bennett", "similarity bennett et", "bennett et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the galnt", ". the galnt family", "the galnt family is", "galnt family is classified", "family is classified as", "is classified as belonging", "classified as belonging to", "as belonging to cazy", "belonging to cazy family", "to cazy family gt27.", "cazy family gt27. defects", "family gt27. defects in", "gt27. defects in one", "defects in one of", "in one of the", "one of the galnt", "the galnt family genes", "family genes galnt3", "mim:601756 can", "601756 can", "can cause familial hyperphosphatemic", "cause familial hyperphosphatemic tumoral", "familial hyperphosphatemic tumoral calcinosis", "tumoral calcinosis hftc", "hftc mim:211900 .", "mim:211900 . hftc is", "211900 . hftc is", ". hftc is a", "hftc is a rare", "is a rare autosomal", "a rare autosomal recessive", "rare autosomal recessive severe", "autosomal recessive severe metabolic", "recessive severe metabolic disorder", "severe metabolic disorder characterised", "metabolic disorder characterised by", "disorder characterised by the", "characterised by the progressive", "by the progressive deposition", "the progressive deposition of", "progressive deposition of calcium", "deposition of calcium phosphate", "of calcium phosphate crystals", "calcium phosphate crystals in", "phosphate crystals in the", "crystals in the skin", "the skin soft", "skin soft tissues", "soft tissues and sometimes", "tissues and sometimes bone", "sometimes bone chefetz", "bone chefetz et", "chefetz et al. 2005", "et al. 2005 .", "al. 2005 . the", "2005 . the biochemical", ". the biochemical observation", "the biochemical observation is", "biochemical observation is hyperphosphatemia", "is hyperphosphatemia caused", "hyperphosphatemia caused by", "caused by increased renal", "by increased renal absorption", "increased renal absorption of", "renal absorption of phosphate", "of phosphate chefetz", "phosphate chefetz et", "al. 2005 ichikawa", "2005 ichikawa et", "ichikawa et al. 2005", "al. 2005 . some", "2005 . some patients", ". some patients manifest", "some patients manifest recurrent", "manifest recurrent transient", "transient painful swellings", "painful swellings of the", "swellings of the long", "of the long bones", "the long bones with", "long bones with radiological", "bones with radiological evidence", "with radiological evidence of", "radiological evidence of periosteal", "evidence of periosteal reaction", "of periosteal reaction and", "periosteal reaction and cortical", "reaction and cortical hyperostosis", "cortical hyperostosis frishberg", "hyperostosis frishberg et", "frishberg et al. 2005", "the family of udp galnac:polypeptide", "family of udp galnac:polypeptide n", "of udp galnac:polypeptide n acetylgalactosaminyltransferases", "galnac:polypeptide n acetylgalactosaminyltransferases galnac", "n acetylgalactosaminyltransferases galnac transferases", "transferases galnts carry", "galnts carry out the", "carry out the addition of", "out the addition of n", "the addition of n acetylgalactosamine", "of n acetylgalactosamine galnac", "acetylgalactosamine galnac on", "on serine threonine or", "serine threonine or possibly", "threonine or possibly tyrosine residues", "or possibly tyrosine residues on", "possibly tyrosine residues on a", "tyrosine residues on a wide", "residues on a wide variety", "on a wide variety of", "a wide variety of proteins", "variety of proteins most", "of proteins most commonly", "proteins most commonly associated", "most commonly associated with mucins.", "associated with mucins. this", "with mucins. this is", "mucins. this is the", "this is the initial reaction", "is the initial reaction in", "the initial reaction in the", "initial reaction in the biosynthesis", "reaction in the biosynthesis of", "in the biosynthesis of galnac", "the biosynthesis of galnac type", "biosynthesis of galnac type o", "of galnac type o linked", "galnac type o linked oligosaccharides", "o linked oligosaccharides wandall", "linked oligosaccharides wandall et", "oligosaccharides wandall et al.", "wandall et al. 1997 .", "et al. 1997 . this", "al. 1997 . this reaction", "1997 . this reaction takes", ". this reaction takes place", "this reaction takes place in", "reaction takes place in the", "takes place in the golgi", "place in the golgi apparatus", "the golgi apparatus rottger", "golgi apparatus rottger et", "apparatus rottger et al.", "rottger et al. 1998 .", "et al. 1998 . there", "al. 1998 . there are", "1998 . there are 20", ". there are 20 known", "there are 20 known members", "are 20 known members of", "20 known members of the", "known members of the galnt", "members of the galnt family", "the galnt family 15", "galnt family 15 of", "family 15 of which", "15 of which have been", "of which have been characterised", "which have been characterised and", "have been characterised and 5", "been characterised and 5 candidate", "characterised and 5 candidate members", "and 5 candidate members which", "5 candidate members which are", "candidate members which are thought", "members which are thought to", "which are thought to belong", "are thought to belong to", "thought to belong to this", "to belong to this family", "belong to this family based", "to this family based on", "this family based on sequence", "family based on sequence similarity", "on sequence similarity bennett", "sequence similarity bennett et", "similarity bennett et al.", "bennett et al. 2012 .", "et al. 2012 . the", "al. 2012 . the galnt", "2012 . the galnt family", ". the galnt family is", "the galnt family is classified", "galnt family is classified as", "family is classified as belonging", "is classified as belonging to", "classified as belonging to cazy", "as belonging to cazy family", "belonging to cazy family gt27.", "to cazy family gt27. defects", "cazy family gt27. defects in", "family gt27. defects in one", "gt27. defects in one of", "defects in one of the", "in one of the galnt", "one of the galnt family", "of the galnt family genes", "galnt family genes galnt3", "genes galnt3 mim:601756", "mim:601756 can cause", "601756 can cause", "can cause familial hyperphosphatemic tumoral", "cause familial hyperphosphatemic tumoral calcinosis", "hyperphosphatemic tumoral calcinosis hftc", "calcinosis hftc mim:211900", "hftc mim:211900 . hftc", "mim:211900 . hftc is a", "211900 . hftc is a", ". hftc is a rare", "hftc is a rare autosomal", "is a rare autosomal recessive", "a rare autosomal recessive severe", "rare autosomal recessive severe metabolic", "autosomal recessive severe metabolic disorder", "recessive severe metabolic disorder characterised", "severe metabolic disorder characterised by", "metabolic disorder characterised by the", "disorder characterised by the progressive", "characterised by the progressive deposition", "by the progressive deposition of", "the progressive deposition of calcium", "progressive deposition of calcium phosphate", "deposition of calcium phosphate crystals", "of calcium phosphate crystals in", "calcium phosphate crystals in the", "phosphate crystals in the skin", "in the skin soft", "the skin soft tissues", "skin soft tissues and", "soft tissues and sometimes bone", "and sometimes bone chefetz", "sometimes bone chefetz et", "bone chefetz et al.", "chefetz et al. 2005 .", "et al. 2005 . the", "al. 2005 . the biochemical", "2005 . the biochemical observation", ". the biochemical observation is", "the biochemical observation is hyperphosphatemia", "observation is hyperphosphatemia caused", "is hyperphosphatemia caused by", "hyperphosphatemia caused by increased", "caused by increased renal absorption", "by increased renal absorption of", "increased renal absorption of phosphate", "absorption of phosphate chefetz", "of phosphate chefetz et", "phosphate chefetz et al.", "et al. 2005 ichikawa", "al. 2005 ichikawa et", "2005 ichikawa et al.", "ichikawa et al. 2005 .", "et al. 2005 . some", "al. 2005 . some patients", "2005 . some patients manifest", ". some patients manifest recurrent", "patients manifest recurrent transient", "recurrent transient painful", "transient painful swellings of", "painful swellings of the long", "swellings of the long bones", "of the long bones with", "the long bones with radiological", "long bones with radiological evidence", "bones with radiological evidence of", "with radiological evidence of periosteal", "radiological evidence of periosteal reaction", "evidence of periosteal reaction and", "of periosteal reaction and cortical", "periosteal reaction and cortical hyperostosis", "and cortical hyperostosis frishberg", "cortical hyperostosis frishberg et", "hyperostosis frishberg et al.", "frishberg et al. 2005 ." ] }, { "record_id": "GLY_000594_1_1391", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5083632", "r hsa", "hsa 5083632", "r hsa 5083632" ] }, { "record_id": "GLY_000594_1_1391", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective c1galt1c1", "c1galt1c1 causes", "causes tnps", "defective c1galt1c1 causes", "c1galt1c1 causes tnps", "defective c1galt1c1 causes tnps", "glycoprotein n", "n acetylgalactosamine", "acetylgalactosamine 3", "3 beta", "beta galactosyltransferase", "galactosyltransferase 1", "mediates the", "the transfer", "transfer of", "of galactose", "from udp", "udp galactose", "galactose to", "to single", "single o", "o linked", "linked galnac", "galnac residues", "tn antigens", "to form", "form core", "core 1", "1 structures", "structures on", "on glycoproteins.", "glycoproteins. c1galt1", "c1galt1 is", "is active", "active when", "when in", "in complex", "complex with", "with the", "the molecular", "molecular chaperone", "chaperone c1galt1c1", "aka cosmc", "which assists", "assists the", "the folding", "folding and/or", "and/or stability", "stability of", "of c1galt1.", "c1galt1. defects", "defects in", "in c1galt1c1", "causes somatic", "somatic tn", "tn polyagglutination", "polyagglutination syndrome", "characterised by", "by the", "the polyagglutination", "polyagglutination of", "of erythrocytes", "erythrocytes by", "by naturally", "naturally occurring", "occurring anti", "anti tn", "tn antibodies", "antibodies following", "following exposure", "exposure of", "of the", "the tn", "tn antigen", "antigen on", "on their", "their surface.", "surface. defects", "c1galt1c1 render", "render c1galt1", "c1galt1 inactive", "inactive and", "and results", "results in", "in the", "the accumulation", "accumulation of", "the incompletely", "incompletely glycosylated", "glycosylated tn", "tn antigen.", "antigen. the", "antigen is", "is tumour", "tumour associated", "found in", "in a", "a majority", "majority of", "of human", "human carcinomas", "and is", "is not", "not normally", "normally expressed", "expressed in", "in peripheral", "peripheral tissues", "tissues or", "or blood", "blood cells", "crew et", "et al.", "al. 2008", "ju et", "al. 2014", "2014 .", ". c1galt1", "c1galt1 and", "and c1galt1c1", "c1galt1c1 belong", "belong to", "to the", "the cazy", "cazy family", "family gt31", "www.cazy.org .", "glycoprotein n acetylgalactosamine", "n acetylgalactosamine 3", "acetylgalactosamine 3 beta", "3 beta galactosyltransferase", "beta galactosyltransferase 1", "1 c1galt1", "c1galt1 mim:610555", "mim:610555 mediates", "610555 mediates", "mediates the transfer", "the transfer of", "transfer of galactose", "galactose gal", "gal from", "from udp galactose", "udp galactose to", "galactose to single", "to single o", "single o linked", "o linked galnac", "linked galnac residues", "residues tn", "antigens to", "to form core", "form core 1", "core 1 structures", "1 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tn", "anti tn antibodies", "tn antibodies following", "antibodies following exposure", "following exposure of", "exposure of the", "of the tn", "the tn antigen", "tn antigen on", "antigen on their", "on their surface.", "their surface. defects", "surface. defects in", "in c1galt1c1 render", "c1galt1c1 render c1galt1", "render c1galt1 inactive", "c1galt1 inactive and", "inactive and results", "and results in", "results in the", "in the accumulation", "the accumulation of", "accumulation of the", "of the incompletely", "the incompletely glycosylated", "incompletely glycosylated tn", "glycosylated tn antigen.", "tn antigen. the", "antigen. the tn", "tn antigen is", "antigen is tumour", "is tumour associated", "associated found", "found in a", "in a majority", "a majority of", "majority of human", "of human carcinomas", "carcinomas and", "and is not", "is not normally", "not normally expressed", "normally expressed in", "expressed in peripheral", "in peripheral tissues", "peripheral tissues or", "tissues or blood", "or blood cells", "cells crew", "crew et al.", "et al. 2008", "2008 ju", "ju et al.", "et al. 2014", "al. 2014 .", "2014 . c1galt1", ". c1galt1 and", "c1galt1 and c1galt1c1", "and c1galt1c1 belong", "c1galt1c1 belong to", "belong to the", "to the cazy", "the cazy family", "cazy family gt31", "gt31 www.cazy.org", "glycoprotein n acetylgalactosamine 3", "n acetylgalactosamine 3 beta", "acetylgalactosamine 3 beta galactosyltransferase", "3 beta galactosyltransferase 1", "galactosyltransferase 1 c1galt1", "mim:610555 mediates the", "610555 mediates the", "mediates the transfer of", "the transfer of galactose", "of galactose gal", "gal from udp", "from udp galactose to", "udp galactose to single", "galactose to single o", "to single o linked", "single o linked galnac", "o linked galnac residues", "galnac residues tn", "residues tn antigens", "tn antigens to", "antigens to form", "to form core 1", "form core 1 structures", "core 1 structures on", "1 structures on glycoproteins.", "structures on glycoproteins. c1galt1", "on glycoproteins. c1galt1 is", "glycoproteins. c1galt1 is active", "c1galt1 is active when", "is active when in", "active when in complex", "when in complex with", "in complex with the", "complex with the molecular", "with the molecular chaperone", "the molecular chaperone c1galt1c1", "chaperone c1galt1c1 aka", "c1galt1c1 aka cosmc", "aka cosmc mim:300611", "mim:300611 which assists", "300611 which assists", "which assists the folding", "assists the folding and/or", "the folding and/or stability", "folding and/or stability of", "and/or stability of c1galt1.", "stability of c1galt1. defects", "of c1galt1. defects in", "c1galt1. defects in c1galt1c1", "defects in c1galt1c1 causes", "in c1galt1c1 causes somatic", "c1galt1c1 causes somatic tn", "causes somatic tn polyagglutination", "somatic tn polyagglutination syndrome", "polyagglutination syndrome tnps", "mim:300622 characterised", "300622 characterised", 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active", "glycoproteins. c1galt1 is active when", "c1galt1 is active when in", "is active when in complex", "active when in complex with", "when in complex with the", "in complex with the molecular", "complex with the molecular chaperone", "with the molecular chaperone c1galt1c1", "molecular chaperone c1galt1c1 aka", "chaperone c1galt1c1 aka cosmc", "cosmc mim:300611 which", "mim:300611 which assists the", "300611 which assists the", "which assists the folding and/or", "assists the folding and/or stability", "the folding and/or stability of", "folding and/or stability of c1galt1.", "and/or stability of c1galt1. defects", "stability of c1galt1. defects in", "of c1galt1. defects in c1galt1c1", "c1galt1. defects in c1galt1c1 causes", "defects in c1galt1c1 causes somatic", "in c1galt1c1 causes somatic tn", "c1galt1c1 causes somatic tn polyagglutination", "causes somatic tn polyagglutination syndrome", "tn polyagglutination syndrome tnps", "syndrome tnps mim:300622", "mim:300622 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results", "c1galt1 inactive and results in", "inactive and results in the", "and results in the accumulation", "results in the accumulation of", "in the accumulation of the", "the accumulation of the incompletely", "accumulation of the incompletely glycosylated", "of the incompletely glycosylated tn", "the incompletely glycosylated tn antigen.", "incompletely glycosylated tn antigen. the", "glycosylated tn antigen. the tn", "tn antigen. the tn antigen", "antigen. the tn antigen is", "the tn antigen is tumour", "tn antigen is tumour associated", "is tumour associated found", "tumour associated found in", "associated found in a", "found in a majority of", "in a majority of human", "a majority of human carcinomas", "of human carcinomas and", "human carcinomas and is", "carcinomas and is not", "and is not normally expressed", "is not normally expressed in", "not normally expressed in peripheral", "normally expressed in peripheral tissues", "expressed in peripheral tissues or", "in 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inner", "the inner walls", "inner walls of", "walls of the", "of the colon", "the colon and", "colon and rectum", "rectum guda", "guda et al.", "et al. 2009", "2009 clarke", "clarke et al.", "the family of udp", "family of udp galnac:polypeptide", "of udp galnac:polypeptide n", "udp galnac:polypeptide n acetylgalactosaminyltransferases", "n acetylgalactosaminyltransferases galnac", "acetylgalactosaminyltransferases galnac transferases", "galnac transferases galnts", "galnts carry out", "carry out the addition", "out the addition of", "the addition of n", "addition of n acetylgalactosamine", "of n acetylgalactosamine on", "n acetylgalactosamine on serine", "on serine threonine", "serine threonine or", "threonine or possibly tyrosine", "or possibly tyrosine residues", "possibly tyrosine residues on", "tyrosine residues on a", "residues on a wide", "on a wide variety", "a wide variety of", "wide variety of proteins", "of proteins and", "proteins and most", "and most commonly associated", 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rectum guda", "rectum guda et", "guda et al. 2009", "al. 2009 clarke", "2009 clarke et", "clarke et al. 2012", "the family of udp galnac:polypeptide", "family of udp galnac:polypeptide n", "of udp galnac:polypeptide n acetylgalactosaminyltransferases", "galnac:polypeptide n acetylgalactosaminyltransferases galnac", "n acetylgalactosaminyltransferases galnac transferases", "transferases galnts carry", "galnts carry out the", "carry out the addition of", "out the addition of n", "the addition of n acetylgalactosamine", "addition of n acetylgalactosamine on", "of n acetylgalactosamine on serine", "acetylgalactosamine on serine threonine", "on serine threonine or", "serine threonine or possibly", "threonine or possibly tyrosine residues", "or possibly tyrosine residues on", "possibly tyrosine residues on a", "tyrosine residues on a wide", "residues on a wide variety", "on a wide variety of", "a wide variety of proteins", "variety of proteins and", "of proteins and most", "proteins and most 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one", "gt27. defects in one of", "defects in one of the", "in one of the galnt", "one of the galnt family", "the galnt family galnt12", "family galnt12 guo", "galnt12 guo et al.", "al. 2002 mim:", "2002 mim: 610290", "mim: 610290 can result", " 610290 can result", "610290 can result in", "can result in decreased glycosylation", "result in decreased glycosylation of", "in decreased glycosylation of mucins", "glycosylation of mucins mainly", "of mucins mainly expressed", "mucins mainly expressed in", "mainly expressed in the digestive", "expressed in the digestive organs", "in the digestive organs such", "the digestive organs such as", "digestive organs such as the", "organs such as the stomach", "as the stomach small", "the stomach small intestine", "stomach small intestine and", "intestine and colon and", "and colon and may", "colon and may play", "and may play a role", "may play a role in", "play a role in colorectal", "a role in colorectal cancer", "role in colorectal cancer 1", 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"lc moiety into the cytosol", "moiety into the cytosol of", "into the cytosol of targeted", "the cytosol of targeted cells", "of targeted cells montal", "targeted cells montal 2010", "montal 2010 and", "2010 and the", "and the botg lc can", "the botg lc can cleave", "botg lc can cleave vesicle", "lc can cleave vesicle associated", "can cleave vesicle associated membrane", "cleave vesicle associated membrane proteins", "vesicle associated membrane proteins 1", "associated membrane proteins 1 and", "membrane proteins 1 and 2", "1 and 2 vamp1", "and 2 vamp1 and", "2 vamp1 and 2", "vamp1 and 2 on", "and 2 on the", "2 on the cytosolic", "on the cytosolic face of", "the cytosolic face of the", "cytosolic face of the synaptic", "face of the synaptic vesicle", "of the synaptic vesicle membrane", "synaptic vesicle membrane schiavo", "vesicle membrane schiavo et", "membrane schiavo et al.", "et al. 1994 yamasaki", "al. 1994 yamasaki et", "1994 yamasaki et al.", "yamasaki et al. 1994 .", "et al. 1994 . these", "al. 1994 . these four", "1994 . these four events", ". these four events are", "these four events are annotated", "four events are annotated here." ] }, { "record_id": "GLY_000594_1_1400", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "532668", "r hsa", "hsa 532668", "r hsa 532668" ] }, { "record_id": "GLY_000594_1_1400", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "n glycan", "glycan trimming", "trimming in", "in the", "the er", "er and", "and calnexin/calreticulin", "calnexin/calreticulin cycle", "n glycan trimming", "glycan trimming in", "trimming in the", "in the er", "the er and", "er and calnexin/calreticulin", "and calnexin/calreticulin cycle", "n glycan trimming in", "glycan trimming in the", "trimming in the er", "in the er and", "the er and calnexin/calreticulin", "er and calnexin/calreticulin cycle", "n glycan trimming in the", "glycan trimming in the er", 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many unknown points in", "many unknown points in this", "unknown points in this process", "in this process as", "this process as it", "process as it is", "as it is known that", "it is known that even", "is known that even proteins", "known that even proteins without", "that even proteins without n", "even proteins without n glycosylation", "proteins without n glycosylation sites", "without n glycosylation sites can", "n glycosylation sites can be", "glycosylation sites can be folded", "sites can be folded properly", "be folded properly caramelo", "folded properly caramelo jj", "properly caramelo jj and", "caramelo jj and parodi aj", "and parodi aj 2008", "parodi aj 2008 ." ] }, { "record_id": "GLY_000594_1_1401", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5357609", "r hsa", "hsa 5357609", "r hsa 5357609" ] }, { "record_id": "GLY_000594_1_1401", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycogen storage", "storage disease", "disease type", "type ii", "glycogen storage disease", "storage disease type", "disease type ii", "ii gaa", "glycogen storage disease type", "storage disease type ii", "type ii gaa", "glycogen storage disease type ii", "disease type ii gaa", "gsd ii", "pompe's disease", "is caused", "caused by", "by mutations", "mutations that", "that reduce", "reduce or", "or eliminate", "eliminate the", "the activity", "activity of", "of lysosomal", "lysosomal alpha", "alpha glucosidase", "hers 1963", "1963 .", ". the", "the presentation", "presentation of", "of gsd", "ii varies", "varies with", "with the", "the severity", "severity of", "of the", "the mutation:", "mutation: patients", "patients with", "with little", "little or", "or no", "no gaa", "gaa activity", "activity are", "are affected", "affected shortly", "shortly after", "after birth", "birth and", "and multiple", "multiple tissues", "tissues are", "are severely", "severely affected.", "affected. 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teeth and", "hair and teeth and myocardiopathy", "teeth and myocardiopathy baric", "and myocardiopathy baric et", "myocardiopathy baric et al.", "baric et al. 2004 ." ] }, { "record_id": "GLY_000594_1_1408", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579002", "r hsa", "hsa 5579002", "r hsa 5579002" ] }, { "record_id": "GLY_000594_1_1408", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective ugt1a1", "ugt1a1 causes", "causes hyperbilirubinemia", "defective ugt1a1 causes", "ugt1a1 causes hyperbilirubinemia", "defective ugt1a1 causes hyperbilirubinemia", "udp glucuronosyltransferases", "play a", "a major", "major role", "role in", "in the", "the conjugation", "conjugation and", "and therefore", "therefore elimination", "elimination of", "of potentially", "potentially toxic", "toxic xenobiotics", "xenobiotics and", "and endogenous", "endogenous compounds.", "compounds. the", "the 1", "1 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"gilbs mim:143500", "mim:143500 and", "143500 and", "and transient familial", "transient familial neonatal", "familial neonatal hyperbilirubinemia", "hyperbilirubinemia hblrtfn", "hblrtfn mim:237900", "mim:237900 to", "237900 to", "to the more", "the more severe", "more severe crigler", "severe crigler najjar", "crigler najjar syndromes", "najjar syndromes 1", "syndromes 1 and", "1 and 2", "2 cn1", "cn1 cn2", "cn2 mim:218800", "mim:218800 and mim:606785", "218800 and 606785", "sticova & jirsa", "& jirsa 2013", "2013 strassburg", "2010 udomuksorn", "udomuksorn et al.", "et al. 2007", "2007 costa", "2006 maruo", "maruo et al.", "et al. 2000", "al. 2000 .", "udp glucuronosyltransferases ugts", "ugts play a", "play a major role", "a major role in", "major role in the", "role in the conjugation", "in the conjugation and", "the conjugation and therefore", "conjugation and therefore elimination", "and therefore elimination of", "therefore elimination of potentially", "elimination of 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breakdown. defects in ugt1a1", "breakdown. defects in ugt1a1 can", "defects in ugt1a1 can cause", "in ugt1a1 can cause hyperbilirubinemia", "ugt1a1 can cause hyperbilirubinemia syndromes", "can cause hyperbilirubinemia syndromes ranging", "cause hyperbilirubinemia syndromes ranging from", "hyperbilirubinemia syndromes ranging from mild", "syndromes ranging from mild forms", "ranging from mild forms such", "from mild forms such as", "mild forms such as gilbert", "forms such as gilbert syndrome", "as gilbert syndrome gilbs", "syndrome gilbs mim:143500", "gilbs mim:143500 and", "mim:143500 and transient familial", "143500 and transient familial", "and transient familial neonatal hyperbilirubinemia", "familial neonatal hyperbilirubinemia hblrtfn", "hyperbilirubinemia hblrtfn mim:237900", "hblrtfn mim:237900 to", "mim:237900 to the more", "237900 to the more", "to the more severe crigler", "the more severe crigler najjar", "more severe crigler najjar syndromes", "severe crigler najjar syndromes 1", "crigler najjar syndromes 1 and", "najjar syndromes 1 and 2", "1 and 2 cn1", "2 cn1 cn2", "cn1 cn2 mim:218800", "cn2 mim:218800 and mim:606785", "and mim:606785 sticova", "mim:606785 sticova &", "606785 sticova &", "& jirsa 2013 strassburg", "jirsa 2013 strassburg 2010", "strassburg 2010 udomuksorn et", "2010 udomuksorn et al.", "et al. 2007 costa", "al. 2007 costa 2006", "costa 2006 maruo et", "2006 maruo et al.", "maruo et al. 2000 ." ] }, { "record_id": "GLY_000594_1_1409", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579009", "r hsa", "hsa 5579009", "r hsa 5579009" ] }, { "record_id": "GLY_000594_1_1409", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cyp11b2", "cyp11b2 causes", "causes cmo", "cmo 1", "1 deficiency", "defective cyp11b2 causes", "cyp11b2 causes cmo", "causes cmo 1", "cmo 1 deficiency", "defective cyp11b2 causes cmo", "cyp11b2 causes cmo 1", "causes cmo 1 deficiency", "defective cyp11b2 causes cmo 1", "cyp11b2 causes cmo 1 deficiency", "cytochrome p450", "p450 11b2", "cyp11b2 aka", "aka aldosterone", "aldosterone hydroxylase", "is an", "an enzyme", "enzyme necessary", "necessary for", "for aldosterone", "aldosterone biosynthesis", "biosynthesis via", "via corticosterone", "and 18", "18 hydroxycorticosterone", "18hcorst .", ". defects", "defects in", "in cyp11b2", "cyp11b2 results", "results in", "in disorders", "disorders of", "of aldosterone", "aldosterone synthesis.", "synthesis. corticosterone", "corticosterone methyloxidase", "methyloxidase 1", "1 and", "and 2", "2 deficiencies", "mim:203400 and", "203400 and", "and cmo", "cmo 2", "2 deficiency", "are autosomal", "autosomal recessive", "recessive disorders", "mitsuuchi et", "et al.", "al. 1993", "bureik et", "al. 2002", "2002 .", ". in", "in cmo", "aldosterone is", "is undetectable", "undetectable in", "in plasma", "while its", "its immediate", "immediate precursor", "is low", "low or", "or normal.", "normal. in", "aldosterone can", "can be", "be low", "or normal", "but at", "at the", "the expense", "expense of", "of increased", "increased secretion", "secretion of", "of 18hcorst.", "18hcorst. patients", "patients with", "with cmo", "deficiency have", "have elevated", "elevated plasma", "plasma 18", "18 hydroxycorticosterone/aldosterone", "hydroxycorticosterone/aldosterone ratios.", "cytochrome p450 11b2", "11b2 mitochondrial", "mitochondrial cyp11b2", "cyp11b2 aka aldosterone", "aka aldosterone hydroxylase", "hydroxylase is", "is an enzyme", "an enzyme necessary", "enzyme necessary for", "necessary for aldosterone", "for aldosterone biosynthesis", "aldosterone biosynthesis via", "biosynthesis via corticosterone", "corticosterone corst", "corst and", "and 18 hydroxycorticosterone", "hydroxycorticosterone 18hcorst", "18hcorst . defects", ". defects in", "defects in cyp11b2", "in cyp11b2 results", "cyp11b2 results in", "results in disorders", "in disorders of", "disorders of aldosterone", "of aldosterone synthesis.", "aldosterone synthesis. corticosterone", "synthesis. corticosterone methyloxidase", "corticosterone methyloxidase 1", "methyloxidase 1 and", "1 and 2", "and 2 deficiencies", "deficiencies cmo", "1 mim:203400", "mim:203400 and cmo", "203400 and cmo", "and cmo 2", "cmo 2 deficiency", "deficiency mim:61060", "mim:61060 are", "61060 are", "are autosomal recessive", "autosomal recessive disorders", "recessive disorders of", "of aldosterone biosynthesis", "biosynthesis mitsuuchi", "mitsuuchi et al.", "et al. 1993", "1993 bureik", "bureik et al.", "et al. 2002", "al. 2002 .", "2002 . in", ". in cmo", "in cmo 1", "deficiency aldosterone", "aldosterone is undetectable", "is undetectable in", "undetectable in plasma", "plasma while", "while its immediate", "its immediate precursor", "precursor 18hcorst", "18hcorst is", "is low or", "low or normal.", "or normal. in", "normal. in cmo", "in cmo 2", "aldosterone can be", "can be low", "be low or", "low or normal", "normal but", "but at the", "at the expense", "the expense of", "expense of increased", "of increased secretion", "increased secretion of", "secretion of 18hcorst.", "of 18hcorst. patients", "18hcorst. patients with", "patients with cmo", "with cmo 2", "2 deficiency have", "deficiency have elevated", "have elevated plasma", "elevated plasma 18", "plasma 18 hydroxycorticosterone/aldosterone", "18 hydroxycorticosterone/aldosterone ratios.", "p450 11b2 mitochondrial", "mitochondrial cyp11b2 aka", "cyp11b2 aka aldosterone hydroxylase", "aldosterone hydroxylase is", "hydroxylase is an", "is an enzyme necessary", "an enzyme necessary for", "enzyme necessary for aldosterone", "necessary for aldosterone biosynthesis", "for aldosterone biosynthesis via", "aldosterone biosynthesis via corticosterone", "via corticosterone corst", "corst and 18", "18 hydroxycorticosterone 18hcorst", "hydroxycorticosterone 18hcorst .", "18hcorst . defects in", ". defects in 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cmo", ". in cmo 1", "in cmo 1 deficiency", "1 deficiency aldosterone", "deficiency aldosterone is", "aldosterone is undetectable in", "is undetectable in plasma", "in plasma while", "plasma while its", "while its immediate precursor", "immediate precursor 18hcorst", "18hcorst is low", "is low or normal.", "low or normal. in", "or normal. in cmo", "normal. in cmo 2", "in cmo 2 deficiency", "2 deficiency aldosterone", "deficiency aldosterone can", "aldosterone can be low", "can be low or", "be low or normal", "or normal but", "normal but at", "but at the expense", "at the expense of", "the expense of increased", "expense of increased secretion", "of increased secretion of", "increased secretion of 18hcorst.", "secretion of 18hcorst. patients", "of 18hcorst. patients with", "18hcorst. patients with cmo", "patients with cmo 2", "with cmo 2 deficiency", "cmo 2 deficiency have", "2 deficiency have elevated", "deficiency have elevated plasma", "have elevated plasma 18", "elevated plasma 18 hydroxycorticosterone/aldosterone", "plasma 18 hydroxycorticosterone/aldosterone ratios.", "cytochrome p450 11b2 mitochondrial", "11b2 mitochondrial cyp11b2", "mitochondrial cyp11b2 aka aldosterone", "aka aldosterone hydroxylase is", "aldosterone hydroxylase is an", "hydroxylase is an enzyme", "is an enzyme necessary for", "an enzyme necessary for aldosterone", "enzyme necessary for aldosterone biosynthesis", "necessary for aldosterone biosynthesis via", "for aldosterone biosynthesis via corticosterone", "biosynthesis via corticosterone corst", "corticosterone corst and", "corst and 18 hydroxycorticosterone", "and 18 hydroxycorticosterone 18hcorst", "18 hydroxycorticosterone 18hcorst .", "hydroxycorticosterone 18hcorst . defects", "18hcorst . defects in cyp11b2", ". defects in cyp11b2 results", "defects in cyp11b2 results in", "in cyp11b2 results in disorders", "cyp11b2 results in disorders of", "results in disorders of aldosterone", "in disorders of aldosterone synthesis.", "disorders of aldosterone synthesis. corticosterone", "of aldosterone synthesis. corticosterone methyloxidase", "aldosterone synthesis. corticosterone methyloxidase 1", "synthesis. corticosterone methyloxidase 1 and", "corticosterone methyloxidase 1 and 2", "methyloxidase 1 and 2 deficiencies", "and 2 deficiencies cmo", "2 deficiencies cmo 1", "cmo 1 mim:203400 and", "1 mim:203400 and cmo", "mim:203400 and cmo 2 deficiency", "203400 and cmo 2 deficiency", "cmo 2 deficiency mim:61060", "deficiency mim:61060 are", "mim:61060 are autosomal recessive", "61060 are autosomal recessive", "are autosomal recessive disorders of", "autosomal recessive disorders of aldosterone", "recessive disorders of aldosterone biosynthesis", "of aldosterone biosynthesis mitsuuchi", "aldosterone biosynthesis mitsuuchi et", "biosynthesis mitsuuchi et al.", "et al. 1993 bureik", "al. 1993 bureik et", "1993 bureik et al.", "bureik et al. 2002 .", "et al. 2002 . in", "al. 2002 . in cmo", "2002 . in cmo 1", ". in cmo 1 deficiency", "cmo 1 deficiency aldosterone", "1 deficiency aldosterone is", "deficiency aldosterone is undetectable", "aldosterone is undetectable in plasma", "undetectable in plasma while", "in plasma while its", "plasma while its immediate", "its immediate precursor 18hcorst", "precursor 18hcorst is", "18hcorst is low or", "is low or normal. in", "low or normal. in cmo", "or normal. in cmo 2", "normal. in cmo 2 deficiency", "cmo 2 deficiency aldosterone", "2 deficiency aldosterone can", "deficiency aldosterone can be", "aldosterone can be low or", "can be low or normal", "low or normal but", "or normal but at", "normal but at the", "but at the expense of", "at the expense of increased", "the expense of increased secretion", "expense of increased secretion of", "of increased secretion of 18hcorst.", "increased secretion of 18hcorst. patients", "secretion of 18hcorst. patients with", "of 18hcorst. patients with cmo", "18hcorst. patients with cmo 2", "patients with cmo 2 deficiency", "with cmo 2 deficiency have", "cmo 2 deficiency have elevated", "2 deficiency have elevated plasma", "deficiency have elevated plasma 18", "have elevated plasma 18 hydroxycorticosterone/aldosterone", "elevated plasma 18 hydroxycorticosterone/aldosterone ratios." ] }, { "record_id": "GLY_000594_1_1410", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579012", "r hsa", "hsa 5579012", "r hsa 5579012" ] }, { "record_id": "GLY_000594_1_1410", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective maoa", "maoa causes", "causes bruns", "defective maoa causes", "maoa causes bruns", "defective maoa causes bruns", "amine oxidase", "flavin containing", "catalyses the", "the oxidative", "oxidative deamination", "deamination of", "of biogenic", "biogenic and", "and dietary", "dietary amines", "the regulation", "regulation of", "of which", "which is", "is critical", "critical for", "for mental", "mental 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"maoa catalyses", "catalyses the oxidative", "the oxidative deamination", "oxidative deamination of", "deamination of biogenic", "of biogenic and", "biogenic and dietary", "and dietary amines", "amines the", "the regulation of", "regulation of which", "of which is", "which is critical", "is critical for", "critical for mental", "for mental state", "mental state homeostasis.", "state homeostasis. maoa", "maoa located", "located on the", "on the mitochondrial", "the mitochondrial outer", "mitochondrial outer membrane", "outer membrane and", "membrane and requiring", "and requiring fad", "requiring fad as", "fad as cofactor", "cofactor weyler", "preferentially oxidises biogenic", "oxidises biogenic amines", "biogenic amines such", "amines such as", "such as 5", "as 5 hydroxytryptamine", "hydroxytryptamine 5ht", "dopamine noradrenaline", "noradrenaline and adrenaline.", "and adrenaline. defects", "adrenaline. defects in", "defects in maoa", "in maoa can", "maoa can cause", "can cause 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hydroxylase/17 20 lyase deficiency", "hydroxylase/17 20 lyase deficiency or", "20 lyase deficiency or isolated", "lyase deficiency or isolated 17", "deficiency or isolated 17 20", "or isolated 17 20 lyase", "isolated 17 20 lyase deficiency", "17 20 lyase deficiency traits", "lyase deficiency traits yanase", "deficiency traits yanase et", "traits yanase et al.", "et al. 1992 kater", "al. 1992 kater &", "1992 kater & biglieri", "& biglieri 1994 fluck", "biglieri 1994 fluck &", "1994 fluck & miller", "& miller 2006 miller", "miller 2006 miller 2012", "2006 miller 2012 ." ] }, { "record_id": "GLY_000594_1_1417", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579030", "r hsa", "hsa 5579030", "r hsa 5579030" ] }, { "record_id": "GLY_000594_1_1417", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cyp19a1", "cyp19a1 causes", "causes aexs", "defective cyp19a1 causes", "cyp19a1 causes aexs", 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"development is normal", "normal bulun", "bulun 2014 .", "cyp19a1 catalyses the", "catalyses the conversion of", "the conversion of androstenedione", "of androstenedione andst", "andst to estrone", "to estrone e1", "estrone e1 .", "e1 . defects in", ". defects in cyp19a1", "defects in cyp19a1 can", "in cyp19a1 can cause", "cyp19a1 can cause aromatase", "can cause aromatase excess", "cause aromatase excess syndrome", "excess syndrome aexs", "mim:139300 and aromatase", "139300 and aromatase", "aromatase deficiency arod", "arod mim:613546 .", "mim:613546 . affected individuals", "613546 . affected individuals", ". affected individuals cannot", "affected individuals cannot synthesise", "individuals cannot synthesise endogenous", "cannot synthesise endogenous estrogens.", "synthesise endogenous estrogens. in", "endogenous estrogens. in females", "estrogens. in females the", "in females the lack", "females the lack of", "the lack of estrogen", "lack of estrogen leads", "of estrogen leads 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"gal1p to form udp", "form udp galactose udp", "udp galactose udp gal", "udp gal and glucose", "gal and glucose 1", "and glucose 1 phosphate. defects", "glucose 1 phosphate. defects in", "1 phosphate. defects in galt", "phosphate. defects in galt can", "defects in galt can cause", "in galt can cause galactosemia", "can cause galactosemia galct", "galactosemia galct mim:230400", "mim:230400 an autosomal", "230400 an autosomal", "an autosomal recessive disorder of", "autosomal recessive disorder of galactose", "recessive disorder of galactose metabolism", "disorder of galactose metabolism presenting", "of galactose metabolism presenting in", "galactose metabolism presenting in neonatals", "metabolism presenting in neonatals that", "presenting in neonatals that causes", "in neonatals that causes jaundice", "that causes jaundice cataracts", "causes jaundice cataracts and", "jaundice cataracts and mental", "and mental retardation bosch", "mental retardation bosch 2006", "retardation bosch 2006 ." ] }, { "record_id": "GLY_000594_1_1420", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619043", "r hsa", "hsa 5619043", "r hsa 5619043" ] }, { "record_id": "GLY_000594_1_1420", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc2a1", "slc2a1 causes", "causes glut1", "glut1 deficiency", "deficiency syndrome", "syndrome 1", "defective slc2a1 causes", "slc2a1 causes glut1", "causes glut1 deficiency", "glut1 deficiency syndrome", "deficiency syndrome 1", "1 glut1ds1", "defective slc2a1 causes glut1", "slc2a1 causes glut1 deficiency", "causes glut1 deficiency syndrome", "glut1 deficiency syndrome 1", "syndrome 1 glut1ds1", "defective slc2a1 causes glut1 deficiency", "slc2a1 causes glut1 deficiency syndrome", "causes glut1 deficiency syndrome 1", "deficiency syndrome 1 glut1ds1", "members of", "of the", "the slc2a", "slc2a family", "family encode", "encode glucose", "glucose 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cells", "cells to", "to take", "take up", "up glucose", "glucose independent", "independent of", "of changes", "changes in", "in blood", "glucose levels.", "levels. defects", "defects in", "in slc2a1", "slc2a1 can", "can cause", "cause neurological", "neurological disorders", "disorders with", "with wide", "wide phenotypic", "phenotypic variability.", "variability. the", "the most", "most severe", "severe 'classic'", "'classic' phenotype", "comprises infantile", "infantile onset", "onset epileptic", "epileptic encephalopathy", "encephalopathy associated", "associated with", "with delayed", "delayed development", "acquired microcephaly", "motor incoordination", "incoordination and", "and spasticity", "brockmann 2009", "de giorgis", "giorgis &", "& veggiotti", "veggiotti 2013", "2013 .", "members of the", "of the slc2a", "the slc2a family", "slc2a family encode", "family encode glucose", "encode glucose transporter", "transporter glut", "glut proteins", "proteins that mediate", "that 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"cells and cells", "and cells of", "cells of the", "of the brain.", "the brain. its", "brain. its low", "its low km", "low km for", "km for glucose", "glucose ~1", "mm relative", "relative to normal", "to normal blood", "normal blood glucose", "blood glucose concentration", "concentration ~5", "mm allows", "allows these cells", "these cells to", "cells to take", "to take up", "take up glucose", "up glucose independent", "glucose independent of", "independent of changes", "of changes in", "changes in blood", "in blood glucose", "blood glucose levels.", "glucose levels. defects", "levels. defects in", "defects in slc2a1", "in slc2a1 can", "slc2a1 can cause", "can cause neurological", "cause neurological disorders", "neurological disorders with", "disorders with wide", "with wide phenotypic", "wide phenotypic variability.", "phenotypic variability. the", "variability. the most", "the most severe", "most severe 'classic'", "severe 'classic' phenotype", "phenotype glut1", "glut1ds1 mim:606777", "comprises infantile onset", "infantile onset epileptic", "onset epileptic encephalopathy", "epileptic encephalopathy associated", "encephalopathy associated with", "associated with delayed", "with delayed development", "development acquired", "microcephaly motor", "motor incoordination and", "incoordination and spasticity", "spasticity brockmann", "2009 de", "de giorgis &", "giorgis & veggiotti", "& veggiotti 2013", "veggiotti 2013 .", "members of the slc2a", "of the slc2a family", "the slc2a family encode", "slc2a family encode glucose", "family encode glucose transporter", "glucose transporter glut", "glut proteins that", "proteins that mediate the", "that mediate the facilitated", "mediate the facilitated diffusion", "the facilitated diffusion of", "facilitated diffusion of glucose", "diffusion of glucose between", "of glucose between the", "glucose between the extracellular", "between the extracellular space", "the extracellular space and", "extracellular space and the", "space and the cytosol.", "and the cytosol. while", "the cytosol. while the", "cytosol. while the monomeric", "while the monomeric protein", "the monomeric protein can", "monomeric protein can form", "protein can form a", "can form a channel", "form a channel and", "a channel and transport", "channel and transport glucose", "transport glucose kinetic", "glucose kinetic studies", "kinetic studies suggest that", "studies suggest that the", "suggest that the functional", "that the functional form", "the functional form of", "functional form of the", "form of the protein", "of the protein is", "the protein is a", "protein is a homotetramer.", "is a homotetramer. slc2a1", "homotetramer. slc2a1 glut1", "glut1 is expressed", "is expressed by many", "expressed by many cell", "by many cell types", "cell types notably", "types notably endothelial", "endothelial cells red", "cells red blood", "red blood cells and", "blood cells and cells", "cells and cells of", "and cells of the", "cells of the brain.", "of the brain. its", "the brain. its low", "brain. its low km", "its low km for", "low km for glucose", "for glucose ~1", "glucose ~1 mm", "~1 mm relative", "mm relative to", "relative to normal blood", "to normal blood glucose", "normal blood glucose concentration", "glucose concentration ~5", "concentration ~5 mm", "~5 mm allows", "mm allows these", "allows these cells to", "these cells to take", "cells to take up", "to take up glucose", "take up glucose independent", "up glucose independent of", "glucose independent of changes", "independent of changes in", "of changes in blood", "changes in blood glucose", "in blood glucose levels.", "blood glucose levels. defects", "glucose levels. defects in", "levels. defects in slc2a1", "defects in slc2a1 can", "in slc2a1 can cause", "slc2a1 can cause neurological", "can cause neurological disorders", "cause neurological disorders with", "neurological disorders with wide", "disorders with wide phenotypic", "with wide phenotypic variability.", "wide phenotypic variability. the", "phenotypic variability. the most", "variability. the most severe", "the most severe 'classic'", "most severe 'classic' phenotype", "'classic' phenotype glut1", "phenotype glut1 deficiency", "mim:606777 comprises", "606777 comprises", "comprises infantile onset epileptic", "infantile onset epileptic encephalopathy", "onset epileptic encephalopathy associated", "epileptic encephalopathy associated with", "encephalopathy associated with delayed", "associated with delayed development", "delayed development acquired", "development acquired microcephaly", "acquired microcephaly motor", "microcephaly motor incoordination", "motor incoordination and spasticity", "and spasticity brockmann", "spasticity brockmann 2009", "brockmann 2009 de", "2009 de giorgis", "de giorgis & veggiotti", "giorgis & veggiotti 2013", "& veggiotti 2013 .", "members of the slc2a family", "of the slc2a family encode", "the slc2a family encode glucose", "slc2a family encode glucose transporter", "encode glucose transporter glut", "transporter glut proteins", "glut proteins that mediate", "proteins that mediate the facilitated", "that mediate the facilitated diffusion", "mediate the facilitated diffusion of", "the facilitated diffusion of glucose", "facilitated diffusion of glucose between", "diffusion of glucose between the", "of glucose between the extracellular", "glucose between the extracellular space", "between the extracellular space and", "the extracellular space and the", "extracellular space and the cytosol.", "space and the cytosol. while", "and the cytosol. while the", "the cytosol. while the monomeric", "cytosol. while the monomeric protein", "while the monomeric protein can", "the monomeric protein can form", "monomeric protein can form a", "protein can form a channel", "can form a channel and", "form a channel and transport", "a channel and transport glucose", "and transport glucose kinetic", "transport glucose kinetic studies", "glucose kinetic studies suggest", "kinetic studies suggest that the", "studies suggest that the functional", "suggest that the functional form", "that the functional form of", "the functional form of the", "functional form of the protein", "form of the protein is", "of the protein is a", "the protein is a homotetramer.", "protein is a homotetramer. slc2a1", "a homotetramer. slc2a1 glut1", "slc2a1 glut1 is", "glut1 is expressed by", "is expressed by many cell", "expressed by many cell types", "many cell types notably", "cell types notably endothelial", "types notably endothelial cells", "notably endothelial cells red", "endothelial cells red blood", "cells red blood cells", "red blood cells and cells", "blood cells and cells of", "cells and cells of the", "and cells of the brain.", "cells of the brain. its", "of the brain. its low", "the brain. its low km", "brain. its low km for", "its low km for glucose", "km for glucose ~1", "for glucose ~1 mm", "~1 mm relative to", "mm relative to normal", "relative to normal blood glucose", "to normal blood glucose concentration", "blood glucose concentration ~5", "glucose concentration ~5 mm", "~5 mm allows these", "mm allows these cells", "allows these cells to take", "these cells to take up", "cells to take up glucose", "to take up glucose independent", "take up glucose independent of", "up glucose independent of changes", "glucose independent of changes in", "independent of changes in blood", "of changes in blood glucose", "changes in blood glucose levels.", "in blood glucose levels. defects", "blood glucose levels. defects in", "glucose levels. defects in slc2a1", "levels. defects in slc2a1 can", "defects in slc2a1 can cause", "in slc2a1 can cause neurological", "slc2a1 can cause neurological disorders", "can cause neurological disorders with", "cause neurological disorders with wide", "neurological disorders with wide phenotypic", "disorders with wide phenotypic variability.", "with wide phenotypic variability. the", "wide phenotypic variability. the most", "phenotypic variability. the most severe", "variability. the most severe 'classic'", "the most severe 'classic' phenotype", "severe 'classic' phenotype glut1", "'classic' phenotype glut1 deficiency", "phenotype glut1 deficiency syndrome", "1 glut1ds1 mim:606777", "mim:606777 comprises infantile", "606777 comprises infantile", "comprises infantile onset epileptic encephalopathy", "infantile onset epileptic encephalopathy associated", "onset epileptic encephalopathy associated with", "epileptic encephalopathy associated with delayed", "encephalopathy associated with delayed development", "with delayed development acquired", "delayed development acquired microcephaly", "acquired microcephaly motor incoordination", "microcephaly motor incoordination and", "incoordination and spasticity brockmann", "and spasticity brockmann 2009", "brockmann 2009 de giorgis", "2009 de giorgis &", "de giorgis & veggiotti 2013", "giorgis & veggiotti 2013 ." ] }, { "record_id": "GLY_000594_1_1421", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619050", "r hsa", "hsa 5619050", "r hsa 5619050" ] }, { "record_id": "GLY_000594_1_1421", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc4a1", "slc4a1 causes", "causes hereditary", "hereditary spherocytosis", "spherocytosis type", "type 4", "distal renal", "renal tubular", "tubular acidosis", "and drta", "drta with", "with hemolytic", "hemolytic anemia", "drta ha", "defective slc4a1 causes", "slc4a1 causes hereditary", "causes hereditary spherocytosis", "hereditary spherocytosis type", "spherocytosis type 4", "4 hsp4", "distal renal tubular", "renal tubular acidosis", "acidosis drta", "drta and", "and drta with", "drta with hemolytic", "with hemolytic anemia", "anemia drta", "defective slc4a1 causes hereditary", "slc4a1 causes hereditary spherocytosis", "causes hereditary spherocytosis type", "hereditary spherocytosis type 4", "type 4 hsp4", "distal renal tubular acidosis", "tubular acidosis drta", "drta and drta", "and drta with hemolytic", "drta with hemolytic anemia", "hemolytic anemia drta", "anemia drta ha", "defective slc4a1 causes hereditary spherocytosis", "slc4a1 causes hereditary spherocytosis type", "causes hereditary spherocytosis type 4", "spherocytosis type 4 hsp4", "hsp4 distal", "renal tubular acidosis drta", "acidosis drta and", "drta and drta with", "and drta with hemolytic anemia", "with hemolytic anemia drta", "hemolytic anemia drta ha", "the proteins", "proteins responsible", "responsible for", "for the", "the exchange", "exchange of", "of cl", "with hco3", "are members", "members of", "of the", "the slc4", "1 3", "and slc26", "7 and", "and 9", "transporter families.", "families. slc4a1", "band 3", "anion exchanger", "exchanger 1", "was the", "the first", "first bicarbonate", "bicarbonate transporter", "transporter gene", "gene to", "to be", "be cloned", "cloned and", "and sequenced.", "sequenced. it", "it is", "is ubiquitous", "ubiquitous throughout", "throughout vertebrates", "vertebrates and", "and in", "in humans", "the major", "major glycoprotein", "glycoprotein present", "present on", "on erythrocytes", "erythrocytes and", "and the", "the basolateral", "basolateral surfaces", "surfaces of", "of kidney", "kidney cells.", "cells. variations", "variations in", "in erythroid", "erythroid slc4a1", "slc4a1 determine", "determine the", "the diego", "diego blood", "blood group", "group system.", "system. mutations", "mutations in", "in the", "the erythrocyte", "erythrocyte form", "form of", "of slc4a1", "slc4a1 can", "can cause", "cause hereditary", "a disorder", "disorder leading", "leading to", "to haemolytic", "haemolytic anaemia", "ha .", ". some", "some mutations", "in slc4a1", "cause distal", "an inability", "inability to", "to acidify", "acidify urine", "tanner 2002", "romero et", "et al.", "al. 2013", "2013 .
              ", "the proteins responsible", "proteins responsible for", "responsible for the", "for the exchange", "the exchange of", "exchange of cl", "cl with", "hco3 are", "are members of", "members of the", "of the slc4", "slc4 1", "3 and", "slc26 3", "3 4", "4 6", "6 7", "7 and 9", "9 transporter", "transporter families. slc4a1", "slc4a1 band", "3 ae1", "ae1 anion", "anion exchanger 1", "1 was", "was the first", "the first bicarbonate", "first bicarbonate transporter", "bicarbonate transporter gene", "transporter gene to", "gene to be", "to be cloned", "be cloned and", "cloned and sequenced.", "and sequenced. it", "sequenced. it is", "it is ubiquitous", "is ubiquitous throughout", "ubiquitous throughout vertebrates", "throughout vertebrates and", "vertebrates and in", "and in humans", "humans is", "is the", "the major glycoprotein", "major glycoprotein present", "glycoprotein present on", "present on erythrocytes", "on erythrocytes and", "erythrocytes and the", "and the basolateral", "the basolateral surfaces", "basolateral surfaces of", "surfaces of kidney", "of kidney cells.", "kidney cells. variations", "cells. variations in", "variations in erythroid", "in erythroid slc4a1", "erythroid slc4a1 determine", "slc4a1 determine the", "determine the diego", "the diego blood", "diego blood group", "blood group system.", "group system. mutations", "system. mutations in", "mutations in the", "in the erythrocyte", "the erythrocyte form", "erythrocyte form of", "form of slc4a1", "of slc4a1 can", "slc4a1 can cause", "can cause hereditary", "cause hereditary spherocytosis", "hsp4 mim:612653", "a disorder leading", "disorder leading to", "leading to haemolytic", "to haemolytic anaemia", "anaemia ha", "ha . some", ". some mutations", "some mutations in", "mutations in slc4a1", "in slc4a1 can", "can cause distal", "distal type1", "type1 renal", "drta mim:179800", "an inability to", "inability to acidify", "to acidify urine", "urine and", "and drta ha", "ha drta", "2002 romero", "romero et al.", "et al. 2013", "al. 2013 .
              ", "the proteins responsible for", "proteins responsible for the", "responsible for the exchange", "for the exchange of", "the exchange of cl", "of cl with", "cl with hco3", "with hco3 are", "hco3 are members", "are members of the", "members of the slc4", "the slc4 1", "slc4 1 3", "1 3 and", "3 and slc26", "and slc26 3", "6 7 and", "and 9 transporter", "9 transporter families.", "families. slc4a1 band", "slc4a1 band 3", "band 3 ae1", "ae1 anion exchanger", "exchanger 1 was", "1 was the", "was the first bicarbonate", "the first bicarbonate transporter", "first bicarbonate transporter gene", "bicarbonate transporter gene to", "transporter gene to be", "gene to be cloned", "to be cloned and", "be cloned and sequenced.", "cloned and sequenced. it", "and sequenced. it is", "sequenced. it is ubiquitous", "it is ubiquitous throughout", "is ubiquitous throughout vertebrates", "ubiquitous throughout vertebrates and", "throughout vertebrates and in", "vertebrates and in humans", "in humans is", "is the major", "the major glycoprotein present", "major glycoprotein present on", "glycoprotein present on erythrocytes", "present on erythrocytes and", "on erythrocytes and the", "erythrocytes and the basolateral", "and the basolateral surfaces", "the basolateral surfaces of", "basolateral surfaces of kidney", "surfaces of kidney cells.", "of kidney cells. variations", "kidney cells. variations in", "cells. variations in erythroid", "variations in erythroid slc4a1", "in erythroid slc4a1 determine", "erythroid slc4a1 determine the", "slc4a1 determine the diego", "determine the diego blood", "the diego blood group", "diego blood group system.", "blood group system. mutations", "group system. mutations in", "system. mutations in the", "mutations in the erythrocyte", "in the erythrocyte form", "the erythrocyte form of", "erythrocyte form of slc4a1", "form of slc4a1 can", "of slc4a1 can cause", "slc4a1 can cause hereditary", "can cause hereditary spherocytosis", "cause hereditary spherocytosis type", "mim:612653 a", "612653 a", "a disorder leading to", "disorder leading to haemolytic", "leading to haemolytic anaemia", "haemolytic anaemia ha", "anaemia ha .", "ha . some mutations", ". some mutations in", "some mutations in slc4a1", "mutations in slc4a1 can", "in slc4a1 can cause", "slc4a1 can cause distal", "cause distal type1", "type1 renal tubular", "mim:179800 an", "179800 an", "an inability to acidify", "inability to acidify urine", "acidify urine and", "urine and drta", "drta ha drta", "ha drta with", "anemia mim:611590", "tanner 2002 romero", "2002 romero et", "romero et al. 2013", "et al. 2013 .
              ", "the proteins responsible for the", "proteins responsible for the exchange", "responsible for the exchange of", "for the exchange of cl", "exchange of cl with", "of cl with hco3", "with hco3 are members", "hco3 are members of", "are members of the slc4", "of the slc4 1", "the slc4 1 3", "1 3 and slc26", "slc26 3 4", "3 4 6", "4 6 7", "6 7 and 9", "7 and 9 transporter", "and 9 transporter families.", "9 transporter families. slc4a1", "transporter families. slc4a1 band", "families. slc4a1 band 3", "3 ae1 anion", "ae1 anion exchanger 1", "anion exchanger 1 was", "exchanger 1 was the", "1 was the first", "was the first bicarbonate transporter", "the first bicarbonate transporter gene", "first bicarbonate transporter gene to", "bicarbonate transporter gene to be", "transporter gene to be cloned", "gene to be cloned and", "to be cloned and sequenced.", "be cloned and sequenced. it", "cloned and sequenced. it is", "and sequenced. it is ubiquitous", "sequenced. it is ubiquitous throughout", "it is ubiquitous throughout vertebrates", "is ubiquitous throughout vertebrates and", "ubiquitous throughout vertebrates and in", "throughout vertebrates and in humans", "and in humans is", "humans is the", "is the major glycoprotein", "the major glycoprotein present on", "major glycoprotein present on erythrocytes", "glycoprotein present on erythrocytes and", "present on erythrocytes and the", "on erythrocytes and the basolateral", "erythrocytes and the basolateral surfaces", "and the basolateral surfaces of", "the basolateral surfaces of kidney", "basolateral surfaces of kidney cells.", "surfaces of kidney cells. variations", "of kidney cells. variations in", "kidney cells. variations in erythroid", "cells. variations in erythroid slc4a1", "variations in erythroid slc4a1 determine", "in erythroid slc4a1 determine the", "erythroid slc4a1 determine the diego", "slc4a1 determine the diego blood", "determine the diego blood group", "the diego blood group system.", "diego blood group system. mutations", "blood group system. mutations in", "group system. mutations in the", "system. mutations in the erythrocyte", "mutations in the erythrocyte form", "in the erythrocyte form of", "the erythrocyte form of slc4a1", "erythrocyte form of slc4a1 can", "form of slc4a1 can cause", "of slc4a1 can cause hereditary", "slc4a1 can cause hereditary spherocytosis", "can cause hereditary spherocytosis type", "cause hereditary spherocytosis type 4", "4 hsp4 mim:612653", "mim:612653 a disorder", "612653 a disorder", "a disorder leading to haemolytic", "disorder leading to haemolytic anaemia", "to haemolytic anaemia ha", "haemolytic anaemia ha .", "anaemia ha . some", "ha . some mutations in", ". some mutations in slc4a1", "some mutations in slc4a1 can", "mutations in slc4a1 can cause", "in slc4a1 can cause distal", "can cause distal type1", "distal type1 renal", "type1 renal tubular acidosis", "acidosis drta mim:179800", "mim:179800 an inability", "179800 an inability", "an inability to acidify urine", "to acidify urine and", "acidify urine and drta", "urine and drta ha", "and drta ha drta", "drta ha drta with", "ha drta with hemolytic", "hemolytic anemia mim:611590", "mim:611590 tanner", "611590 tanner", "tanner 2002 romero et", "2002 romero et al.", "romero et al. 2013 .
              " ] }, { "record_id": "GLY_000594_1_1422", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619056", "r hsa", "hsa 5619056", "r hsa 5619056" ] }, { "record_id": "GLY_000594_1_1422", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective hk1", "hk1 causes", "causes hexokinase", "hexokinase deficiency", "hk deficiency", "defective hk1 causes", "hk1 causes hexokinase", "causes hexokinase deficiency", "deficiency hk", "defective hk1 causes hexokinase", "hk1 causes hexokinase deficiency", "hexokinase deficiency hk", "deficiency hk deficiency", "defective hk1 causes hexokinase deficiency", "causes hexokinase deficiency hk", "hexokinase deficiency hk deficiency", "cytosolic hexokinase", "hexokinase 1", "together with", "with isoforms", "isoforms hk2", "hk2 and", "and 3", "3 and", "and glucokinase", "catalyse the", "the irreversible", "irreversible reaction", "reaction of", "of alpha", "alpha d", "d glucose", "and atp", "atp to", "to form", "form alpha", "glucose 6", "6 phosphate", "and adp", "the first", "first step", "step in", "in glycolysis.", "glycolysis. hk1", "hk1 is", "is the", "the predominant", "predominant isoform", "isoform of", "of the", "the different", "different hks", "hks in", "in tissues", "tissues that", "that utilise", "utilise glucose", "glucose for", "for their", "their physiological", "physiological function", "function such", "such as", "as brain", "platelets and", "and fibroblasts.", "fibroblasts. defects", "defects in", "in hk1", "hk1 can", "can cause", "cause hexokinase", "a rare", "autosomal recessive", "recessive disease", "disease with", "with nonspherocytic", "nonspherocytic hemolytic", "hemolytic anemia", "anemia as", "as the", "predominant clinical", "clinical feature", "kanno 2000", "2000 .", "cytosolic hexokinase 1", "1 hk1", "together with isoforms", "with isoforms hk2", "isoforms hk2 and", "hk2 and 3", "and 3 and", "3 and glucokinase", "glucokinase gck", "catalyse the irreversible", "the irreversible reaction", "irreversible reaction of", "reaction of alpha", "of alpha d", "alpha d glucose", "glucose glc", "glc and", "and atp to", "atp to form", "to form alpha", "form alpha d", "d glucose 6", "glucose 6 phosphate", "phosphate g6p", "g6p and", "adp the", "the first step", "first step in", "step in glycolysis.", "in glycolysis. hk1", "glycolysis. hk1 is", "hk1 is the", "is the predominant", "the predominant isoform", "predominant isoform of", "isoform of the", "of the different", "the different hks", "different hks in", "hks in tissues", "in tissues that", "tissues that utilise", "that utilise glucose", "utilise glucose for", "glucose for their", "for their physiological", "their physiological function", "physiological function such", "function such as", "such as brain", "brain lymphocytes", "lymphocytes erythrocytes", "erythrocytes platelets", "platelets and fibroblasts.", "and fibroblasts. defects", "fibroblasts. defects in", "defects in hk1", "in hk1 can", "hk1 can cause", "can cause hexokinase", "cause hexokinase deficiency", "deficiency mim:235700", "rare autosomal", "autosomal recessive disease", "recessive disease with", "disease with nonspherocytic", "with nonspherocytic hemolytic", "nonspherocytic hemolytic anemia", "hemolytic anemia as", "anemia as the", "as the predominant", "the predominant clinical", "predominant clinical feature", "feature kanno", "kanno 2000 .", "hexokinase 1 hk1", "hk1 together", "together with isoforms hk2", "with isoforms hk2 and", "isoforms hk2 and 3", "hk2 and 3 and", "and 3 and glucokinase", "and glucokinase gck", "gck catalyse", "catalyse the irreversible reaction", "the irreversible reaction of", "irreversible reaction of alpha", "reaction of alpha d", "of alpha d glucose", "d glucose glc", "glc and atp", "and atp to form", "atp to form alpha", "to form alpha d", "form alpha d glucose", "alpha d glucose 6", "d glucose 6 phosphate", "6 phosphate g6p", "g6p and adp", "and adp the", "adp the first", "the first step in", "first step in glycolysis.", "step in glycolysis. hk1", "in glycolysis. hk1 is", "glycolysis. hk1 is the", "hk1 is the predominant", "is the predominant isoform", "the predominant isoform of", "predominant isoform of the", "isoform of the different", "of the different hks", "the different hks in", "different hks in tissues", "hks in tissues that", "in tissues that utilise", "tissues that utilise glucose", "that utilise glucose for", "utilise glucose for their", "glucose for their physiological", "for their physiological function", "their physiological function such", "physiological function such as", "function such as brain", "as brain lymphocytes", "erythrocytes platelets and", "platelets and fibroblasts. defects", "and fibroblasts. defects in", "fibroblasts. defects in hk1", "defects in hk1 can", "in hk1 can cause", "hk1 can cause hexokinase", "can cause hexokinase deficiency", "hk deficiency mim:235700", "mim:235700 a", "235700 a", "a rare autosomal", "rare autosomal recessive", "autosomal recessive disease with", "recessive disease with nonspherocytic", "disease with nonspherocytic hemolytic", "with nonspherocytic hemolytic anemia", "nonspherocytic hemolytic anemia as", "hemolytic anemia as the", "anemia as the predominant", "as the predominant clinical", "the predominant clinical feature", "clinical feature kanno", "feature kanno 2000", "cytosolic hexokinase 1 hk1", "hk1 together with", "together with isoforms hk2 and", "with isoforms hk2 and 3", "isoforms hk2 and 3 and", "hk2 and 3 and glucokinase", "3 and glucokinase gck", "gck catalyse the", "catalyse the irreversible reaction of", "the irreversible reaction of alpha", "irreversible reaction of alpha d", "reaction of alpha d glucose", "alpha d glucose glc", "glucose glc and", "glc and atp to", "and atp to form alpha", "atp to form alpha d", "to form alpha d glucose", "form alpha d glucose 6", "alpha d glucose 6 phosphate", "glucose 6 phosphate g6p", "phosphate g6p and", "and adp the first", "adp the first step", "the first step in glycolysis.", "first step in glycolysis. hk1", "step in glycolysis. hk1 is", "in glycolysis. hk1 is the", "glycolysis. hk1 is the predominant", "hk1 is the predominant isoform", "is the predominant isoform of", "the predominant isoform of the", "predominant isoform of the different", "isoform of the different hks", "of the different hks in", "the different hks in tissues", "different hks in tissues that", "hks in tissues that utilise", "in tissues that utilise glucose", "tissues that utilise glucose for", "that utilise glucose for their", "utilise glucose for their physiological", "glucose for their physiological function", "for their physiological function such", "their physiological function such as", "physiological function such as brain", "such as brain lymphocytes", "brain lymphocytes erythrocytes", "lymphocytes erythrocytes platelets", "erythrocytes platelets and fibroblasts.", "platelets and fibroblasts. defects in", "and fibroblasts. defects in hk1", "fibroblasts. defects in hk1 can", "defects in hk1 can cause", "in hk1 can cause hexokinase", "hk1 can cause hexokinase deficiency", "cause hexokinase deficiency hk", "mim:235700 a rare", "235700 a rare", "a rare autosomal recessive", "rare autosomal recessive disease", "autosomal recessive disease with nonspherocytic", "recessive disease with nonspherocytic hemolytic", "disease with nonspherocytic hemolytic anemia", "with nonspherocytic hemolytic anemia as", "nonspherocytic hemolytic anemia as the", "hemolytic anemia as the predominant", "anemia as the predominant clinical", "as the predominant clinical feature", "predominant clinical feature kanno", "clinical feature kanno 2000", "feature kanno 2000 ." ] }, { "record_id": "GLY_000594_1_1423", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619058", "r hsa", "hsa 5619058", "r hsa 5619058" ] }, { "record_id": "GLY_000594_1_1423", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slco1b3", "slco1b3 causes", "causes hyperbilirubinemia", "rotor type", "defective slco1b3 causes", "slco1b3 causes hyperbilirubinemia", "hyperbilirubinemia rotor", "type hblrr", "defective slco1b3 causes hyperbilirubinemia", "causes hyperbilirubinemia rotor", "hyperbilirubinemia rotor type", "rotor type hblrr", "slco1b3 causes hyperbilirubinemia rotor", "causes hyperbilirubinemia rotor type", "in the", "the body", "solute carrier", "carrier organic", "organic anion", "anion transporter", "transporter family", "family member", "member 1b3", "is expressed", "expressed on", "on the", "the basolateral", "basolateral surfaces", "surfaces of", "of hepatocytes", "hepatocytes and", "and may", "may play", "play a", "a role", "role in", "the uptake", "uptake of", "of bilirubin", "a breakdown", "breakdown product", "product of", "of heme", "heme that", "that requires", "requires conjugation", "conjugation and", "and excretion", "excretion from", "from the", "the body.", "body. defects", "defects in", "in slco1b3", "slco1b3 can", "can cause", "cause hyperbilirubinemia", "an autosomal", "autosomal recessive", "recessive form", "form of", "of primary", "primary conjugated", "conjugated hyperbilirubinemia.", "hyperbilirubinemia. mild", "mild jaundice", "not associated", "associated with", "with hemolysis", "develops shortly", "shortly after", "after birth", "birth or", "or in", "in childhood", "van de", "de steeg", "steeg et", "et al.", "al. 2012", "sticova &", "& jirsa", "jirsa 2013", "keppler 2014", "2014 .", "in the body", "body solute", "solute carrier organic", "carrier organic anion", "organic anion transporter", "anion transporter family", "transporter family member", "family member 1b3", "1b3 slco1b3", "slco1b3 is", "is expressed on", "expressed on the", "on the basolateral", "the basolateral surfaces", "basolateral surfaces of", "surfaces of hepatocytes", "of hepatocytes and", "hepatocytes and may", "and may play", "may play a", "play a role", "a role in", "role in the", "in the uptake", "the uptake of", "uptake of bilirubin", "bilirubin bil", "a breakdown product", "breakdown product of", "product of heme", "of heme that", "heme that requires", "that requires conjugation", "requires conjugation and", "conjugation and excretion", "and excretion from", "excretion from the", "from the body.", "the body. defects", "body. defects in", "defects in slco1b3", "in slco1b3 can", "slco1b3 can cause", "can cause hyperbilirubinemia", "hblrr mim:237450", "an autosomal recessive", "autosomal recessive form", "recessive form of", "form of primary", "of primary conjugated", "primary conjugated hyperbilirubinemia.", "conjugated hyperbilirubinemia. mild", "hyperbilirubinemia. mild jaundice", "jaundice not", "not associated with", "associated with hemolysis", "hemolysis develops", "develops shortly after", "shortly after birth", "after birth or", "birth or in", "or in childhood", "childhood van", "van de steeg", "de steeg et", "steeg et al.", "et al. 2012", "2012 sticova", "sticova & jirsa", "& jirsa 2013", "2013 keppler", "keppler 2014 .", "the body solute", "body solute carrier", "solute carrier organic anion", "carrier organic anion transporter", "organic anion transporter family", "anion transporter family member", "transporter family member 1b3", "member 1b3 slco1b3", "slco1b3 is expressed", "is expressed on the", "expressed on the basolateral", "on the basolateral surfaces", "the basolateral surfaces of", "basolateral surfaces of hepatocytes", "surfaces of hepatocytes and", "of hepatocytes and may", "hepatocytes and may play", "and may play a", "may play a role", "play a role in", "a role in the", "role in the uptake", "in the uptake of", "the uptake of bilirubin", "of bilirubin bil", "bil a", "a breakdown product of", "breakdown product of heme", "product of heme that", "of heme that requires", "heme that requires conjugation", "that requires conjugation and", "requires conjugation and excretion", "conjugation and excretion from", "and excretion from the", "excretion from the body.", "from the body. defects", "the body. defects in", "body. defects in slco1b3", "defects in slco1b3 can", "in slco1b3 can cause", "slco1b3 can cause hyperbilirubinemia", "cause hyperbilirubinemia rotor", "mim:237450 an", "237450 an", "an autosomal recessive form", "autosomal recessive form of", "recessive form of primary", "form of primary conjugated", "of primary conjugated hyperbilirubinemia.", "primary conjugated hyperbilirubinemia. mild", "conjugated hyperbilirubinemia. mild jaundice", "mild jaundice not", "jaundice not associated", "not associated with hemolysis", "with hemolysis develops", "hemolysis develops shortly", "develops shortly after birth", "shortly after birth or", "after birth or in", "birth or in childhood", "in childhood van", "childhood van de", "van de steeg et", "de steeg et al.", "steeg et al. 2012", "al. 2012 sticova", "2012 sticova &", "sticova & jirsa 2013", "jirsa 2013 keppler", "2013 keppler 2014", "in the body solute", "the body solute carrier", "body solute carrier organic", "solute carrier organic anion transporter", "carrier organic anion transporter family", "organic anion transporter family member", "anion transporter family member 1b3", "family member 1b3 slco1b3", "1b3 slco1b3 is", "slco1b3 is expressed on", "is expressed on the basolateral", "expressed on the basolateral surfaces", "on the basolateral surfaces of", "the basolateral surfaces of hepatocytes", "basolateral surfaces of hepatocytes and", "surfaces of hepatocytes and may", "of hepatocytes and may play", "hepatocytes and may play a", "and may play a role", "may play a role in", "play a role in the", "a role in the uptake", "role in the uptake of", "in the uptake of bilirubin", "uptake of bilirubin bil", "bil a breakdown", "a breakdown product of heme", "breakdown product of heme that", "product of heme that requires", "of heme that requires conjugation", "heme that requires conjugation and", "that requires conjugation and excretion", "requires conjugation and excretion from", "conjugation and excretion from the", "and excretion from the body.", "excretion from the body. defects", "from the body. defects in", "the body. defects in slco1b3", "body. defects in slco1b3 can", "defects in slco1b3 can cause", "in slco1b3 can cause hyperbilirubinemia", "can cause hyperbilirubinemia rotor", "cause hyperbilirubinemia rotor type", "type hblrr mim:237450", "mim:237450 an autosomal", "237450 an autosomal", "an autosomal recessive form of", "autosomal recessive form of primary", "recessive form of primary conjugated", "form of primary conjugated hyperbilirubinemia.", "of primary conjugated hyperbilirubinemia. mild", "primary conjugated hyperbilirubinemia. mild jaundice", "hyperbilirubinemia. mild jaundice not", "mild jaundice not associated", "jaundice not associated with", "associated with hemolysis develops", "with hemolysis develops shortly", "hemolysis develops shortly after", "develops shortly after birth or", "shortly after birth or in", "after birth or in childhood", "or in childhood van", "in childhood van de", "childhood van de steeg", "van de steeg et al.", "de steeg et al. 2012", "et al. 2012 sticova", "al. 2012 sticova &", "2012 sticova & jirsa", "& jirsa 2013 keppler", "jirsa 2013 keppler 2014", "2013 keppler 2014 ." ] }, { "record_id": "GLY_000594_1_1424", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619098", "r hsa", "hsa 5619098", "r hsa 5619098" ] }, { "record_id": "GLY_000594_1_1424", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc2a2", "slc2a2 causes", "causes fanconi", "fanconi bickel", "bickel syndrome", "defective slc2a2 causes", "slc2a2 causes fanconi", "causes fanconi bickel", "fanconi bickel syndrome", "syndrome fbs", "defective slc2a2 causes fanconi", "slc2a2 causes fanconi bickel", "causes fanconi bickel syndrome", "bickel syndrome fbs", "defective slc2a2 causes fanconi bickel", "slc2a2 causes fanconi bickel syndrome", "fanconi bickel syndrome fbs", "the reversible", "reversible facilitated", "facilitated diffusion", "diffusion of", "of fructose", "and glucose", "glucose from", "from the", "the cytosol", "cytosol to", "to the", "the extracellular", "extracellular space", "space is", "is mediated", "mediated by", "by the", "the slc2a2", "transporter in", "in the", "the plasma", "plasma membrane.", "membrane. in", "the epithelial", "epithelial cells", "cells of", "of the", "the small", "small intestine", "the basolateral", "basolateral localisation", "localisation of", "of slc2a2", "slc2a2 enables", "enables hexose", "hexose sugars", "sugars derived", "derived from", "the diet", "and taken", "taken up", "up by", "by slc5a1", "slc5a1 and", "and slc2a5", "slc2a5 transporters", "transporters into", 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for insulin secretion", "for insulin secretion and", "insulin secretion and in", "secretion and in the", "and in the liver", "the liver it", "liver it allows", "it allows for bi", "allows for bi directional", "for bi directional glucose", "bi directional glucose transport.", "directional glucose transport. defects", "glucose transport. defects in", "transport. defects in slc2a2", "defects in slc2a2 can", "in slc2a2 can cause", "slc2a2 can cause fanconi", "can cause fanconi bickel", "cause fanconi bickel syndrome", "mim:227810 a", "227810 a", "a rare but well", "rare but well defined", "but well defined disorder", "well defined disorder characterised", "defined disorder characterised by", "disorder characterised by glycogen", "characterised by glycogen accumulation", "glycogen accumulation proximal", "accumulation proximal renal", "proximal renal tubular dysfunction", "tubular dysfunction and", "dysfunction and impaired", "and impaired utilisation of", "impaired utilisation of glucose", "utilisation of glucose and", "of glucose and galactose", "and galactose leturque", "galactose leturque et", "leturque et al. 2009", "al. 2009 douard", "2009 douard &", "douard & ferraris 2013", "& ferraris 2013 .", "the reversible facilitated diffusion of", "reversible facilitated diffusion of fructose", "diffusion of fructose galactose", "fructose galactose and", "galactose and glucose from", "and glucose from the cytosol", "glucose from the cytosol to", "from the cytosol to the", "the cytosol to the extracellular", "cytosol to the extracellular space", "to the extracellular space is", "the extracellular space is mediated", "extracellular space is mediated by", "space is mediated by the", "is mediated by the slc2a2", "by the slc2a2 glut2", "slc2a2 glut2 transporter", "glut2 transporter in the", "transporter in the plasma membrane.", "in the plasma membrane. in", "the plasma membrane. in the", "plasma membrane. in the epithelial", "membrane. in the epithelial cells", "in the epithelial cells of", "the epithelial cells of the", "epithelial cells of the small", "cells of the small intestine", "the small intestine the", "small intestine the basolateral", "intestine the basolateral localisation", "the basolateral localisation of slc2a2", "basolateral localisation of slc2a2 enables", "localisation of slc2a2 enables hexose", "of slc2a2 enables hexose sugars", "slc2a2 enables hexose sugars derived", "enables hexose sugars derived from", "hexose sugars derived from the", "sugars derived from the diet", "from the diet and", "the diet and taken", "diet and taken up", "and taken up by slc5a1", "taken up by slc5a1 and", "up by slc5a1 and slc2a5", "by slc5a1 and slc2a5 transporters", "slc5a1 and slc2a5 transporters into", "and slc2a5 transporters into cells", "transporters into cells to", "into cells to be", "cells to be released", "to be released into the", "be released into the circulation.", "released into the circulation. slc2a2", "into the circulation. slc2a2 is", "the circulation. slc2a2 is a", "circulation. slc2a2 is a low", "slc2a2 is a low affinity", "is a low affinity glucose", "a low affinity glucose transporter", "low affinity glucose transporter expressed", "affinity glucose transporter expressed mainly", "glucose transporter expressed mainly in", "transporter expressed mainly in the", "expressed mainly in the kidney", "in the kidney liver", "the kidney liver and", "kidney liver and pancreatic", "liver and pancreatic beta cells.", "and pancreatic beta cells. in", "pancreatic beta cells. in beta", "beta cells. in beta cells", "in beta cells it", "beta cells it functions", "cells it functions as", "it functions as a glucose", "functions as a glucose sensor", "as a glucose sensor for", "a glucose sensor for insulin", "glucose sensor for insulin secretion", "sensor for insulin secretion and", "for insulin secretion and in", "insulin secretion and in the", "secretion and in the liver", "in the liver it", "the liver it allows", "liver it allows for", "it allows for bi directional", "allows for bi directional glucose", "for bi directional glucose transport.", "bi directional glucose transport. defects", "directional glucose transport. defects in", "glucose transport. defects in slc2a2", "transport. defects in slc2a2 can", "defects in slc2a2 can cause", "in slc2a2 can cause fanconi", "slc2a2 can cause fanconi bickel", "can cause fanconi bickel syndrome", "syndrome fbs mim:227810", "mim:227810 a rare", "227810 a rare", "a rare but well defined", "rare but well defined disorder", "but well defined disorder characterised", "well defined disorder characterised by", "defined disorder characterised by glycogen", "disorder characterised by glycogen accumulation", "by glycogen accumulation proximal", "glycogen accumulation proximal renal", "accumulation proximal renal tubular", "renal tubular dysfunction and", "tubular dysfunction and impaired", "dysfunction and impaired utilisation", "and impaired utilisation of glucose", "impaired utilisation of glucose and", "utilisation of glucose and galactose", "glucose and galactose leturque", "and galactose leturque et", "galactose leturque et al.", "et al. 2009 douard", "al. 2009 douard &", "2009 douard & ferraris", "douard & ferraris 2013 ." ] }, { "record_id": "GLY_000594_1_1425", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619109", "r hsa", "hsa 5619109", "r hsa 5619109" ] }, { "record_id": "GLY_000594_1_1425", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc6a2", "slc6a2 causes", "causes orthostatic", "orthostatic intolerance", "defective slc6a2 causes", "slc6a2 causes orthostatic", "causes orthostatic intolerance", "intolerance oi", "defective slc6a2 causes orthostatic", "slc6a2 causes orthostatic intolerance", "orthostatic intolerance oi", "defective slc6a2 causes orthostatic intolerance", "causes orthostatic intolerance oi", "slc6a2 encodes", "encodes the", "the sodium", "sodium dependent", "dependent noradrenaline", "noradrenaline transporter", "transporter nat1", "nat1 which", "which terminates", "terminates the", "the action", "action of", "of the", "the neurotransmitter", "neurotransmitter noradrenaline", "noradrenaline by", "by transporting", "transporting it", "it from", "from the", "the synapse", "synapse back", "back to", "to its", "its vesicles", "vesicles for", "for storage", "storage and", "and reuse", "broer &", "& gether", "gether 2012", "schweikhard &", "& ziegler", "ziegler 2012", "2012 .", ". slc6a2", "slc6a2 is", "is expressed", "expressed in", "in the", "the cns", "cns and", "and adrenal", "adrenal glands.", "glands. defects", "defects in", "in slc6a2", "slc6a2 can", "can cause", "cause orthostatic", "a syndrome", "syndrome characterised", "characterised by", "by lightheadedness", "fatigue and", "and development", "development of", "of symptoms", "symptoms during", "during upright", "upright standing", "relieved by", "by sitting", "sitting back", "back down", "down again.", "again. plasma", "plasma norepinephrine", "norepinephrine concentration", "concentration is", "is abnormally", "abnormally high", "lambert &", "& lambert", "lambert 2014", "2014 .", "slc6a2 encodes the", "encodes the sodium", "the sodium dependent", "sodium dependent noradrenaline", "dependent noradrenaline transporter", "noradrenaline transporter nat1", "transporter nat1 which", "nat1 which terminates", "which terminates the", "terminates the action", "the action of", "action of the", "of the neurotransmitter", "the neurotransmitter noradrenaline", "neurotransmitter noradrenaline by", "noradrenaline by transporting", "by transporting it", "transporting it from", "it from the", "from the synapse", "the synapse back", "synapse back to", "back to its", "to its vesicles", "its vesicles for", "vesicles for storage", "for storage and", "storage and reuse", "reuse broer", "broer & gether", "& gether 2012", "2012 schweikhard", "schweikhard & ziegler", "& ziegler 2012", "ziegler 2012 .", "2012 . slc6a2", ". slc6a2 is", "slc6a2 is expressed", "is expressed in", "expressed in the", "in the cns", "the cns and", "cns and adrenal", "and adrenal glands.", "adrenal glands. defects", "glands. defects in", "defects in slc6a2", "in slc6a2 can", "slc6a2 can cause", "can cause orthostatic", "cause orthostatic intolerance", "oi mim:604715", "a syndrome characterised", "syndrome characterised by", "characterised by lightheadedness", "lightheadedness fatigue", "fatigue and development", "and development of", "development of symptoms", "of symptoms during", "symptoms during upright", "during upright standing", "standing relieved", "relieved by sitting", "by sitting back", "sitting back down", "back down again.", "down again. plasma", "again. plasma norepinephrine", "plasma norepinephrine concentration", "norepinephrine concentration is", "concentration is abnormally", "is abnormally high", "high lambert", "lambert & lambert", "& lambert 2014", "lambert 2014 .", "slc6a2 encodes the sodium", "encodes the sodium dependent", "the sodium dependent noradrenaline", "sodium dependent noradrenaline transporter", "dependent noradrenaline transporter nat1", "noradrenaline transporter nat1 which", "transporter nat1 which terminates", "nat1 which terminates the", "which terminates the action", "terminates the action of", "the action of the", "action of the neurotransmitter", "of the neurotransmitter noradrenaline", "the neurotransmitter noradrenaline by", "neurotransmitter noradrenaline by transporting", "noradrenaline by transporting it", "by transporting it from", "transporting it from the", "it from the synapse", "from the synapse back", "the synapse back to", "synapse back to its", "back to its vesicles", "to its vesicles for", "its vesicles for storage", "vesicles for storage and", "for storage and reuse", "and reuse broer", "reuse broer &", "broer & gether 2012", "gether 2012 schweikhard", "2012 schweikhard &", "schweikhard & ziegler 2012", "& ziegler 2012 .", "ziegler 2012 . slc6a2", "2012 . slc6a2 is", ". slc6a2 is expressed", "slc6a2 is expressed in", "is expressed in the", "expressed in the cns", "in the cns and", "the cns and adrenal", "cns and adrenal glands.", "and adrenal glands. defects", "adrenal glands. defects in", "glands. defects in slc6a2", "defects in slc6a2 can", "in slc6a2 can cause", "slc6a2 can cause orthostatic", "can cause orthostatic intolerance", "mim:604715 a", "604715 a", "a syndrome characterised by", "syndrome characterised by lightheadedness", "by lightheadedness fatigue", "lightheadedness fatigue and", "fatigue and development of", "and development of symptoms", "development of symptoms during", "of symptoms during upright", "symptoms during upright standing", "upright standing relieved", "standing relieved by", "relieved by sitting back", "by sitting back down", "sitting back down again.", "back down again. plasma", "down again. plasma norepinephrine", "again. plasma norepinephrine concentration", "plasma norepinephrine concentration is", "norepinephrine concentration is abnormally", "concentration is abnormally high", "abnormally high lambert", "high lambert &", "lambert & lambert 2014", "& lambert 2014 .", "slc6a2 encodes the sodium dependent", "encodes the sodium dependent noradrenaline", "the sodium dependent noradrenaline transporter", "sodium dependent noradrenaline transporter nat1", "dependent noradrenaline transporter nat1 which", "noradrenaline transporter nat1 which terminates", "transporter nat1 which terminates the", "nat1 which terminates the action", "which terminates the action of", "terminates the action of the", "the action of the neurotransmitter", "action of the neurotransmitter noradrenaline", "of the neurotransmitter noradrenaline by", "the neurotransmitter noradrenaline by transporting", "neurotransmitter noradrenaline by transporting it", "noradrenaline by transporting it from", "by transporting it from the", "transporting it from the synapse", "it from the synapse back", "from the synapse back to", "the synapse back to its", "synapse back to its vesicles", "back to its vesicles for", "to its vesicles for storage", "its vesicles for storage and", "vesicles for storage and reuse", "storage and reuse broer", "and reuse broer &", "reuse broer & gether", "& gether 2012 schweikhard", "gether 2012 schweikhard &", "2012 schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . slc6a2", "ziegler 2012 . slc6a2 is", "2012 . slc6a2 is expressed", ". slc6a2 is expressed in", "slc6a2 is expressed in the", "is expressed in the cns", "expressed in the cns and", "in the cns and adrenal", "the cns and adrenal glands.", "cns and adrenal glands. defects", "and adrenal glands. defects in", "adrenal glands. defects in slc6a2", "glands. defects in slc6a2 can", "defects in slc6a2 can cause", "in slc6a2 can cause orthostatic", "slc6a2 can cause orthostatic intolerance", "cause orthostatic intolerance oi", "intolerance oi mim:604715", "mim:604715 a syndrome", "604715 a syndrome", "a syndrome characterised by lightheadedness", "characterised by lightheadedness fatigue", "by lightheadedness fatigue and", "lightheadedness fatigue and development", "fatigue and development of symptoms", "and development of symptoms during", "development of symptoms during upright", "of symptoms during upright standing", "during upright standing relieved", "upright standing relieved by", "standing relieved by sitting", "relieved by sitting back down", "by sitting back down again.", "sitting back down again. plasma", "back down again. plasma norepinephrine", "down again. plasma norepinephrine concentration", "again. plasma norepinephrine concentration is", "plasma norepinephrine concentration is abnormally", "norepinephrine concentration is abnormally high", "is abnormally high lambert", "abnormally high lambert &", "high lambert & lambert", "lambert & lambert 2014 ." ] }, { "record_id": "GLY_000594_1_1426", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619110", "r hsa", "hsa 5619110", "r hsa 5619110" ] }, { "record_id": "GLY_000594_1_1426", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slco1b1", "slco1b1 causes", "causes hyperbilirubinemia", "rotor type", "defective slco1b1 causes", "slco1b1 causes hyperbilirubinemia", "hyperbilirubinemia rotor", "type hblrr", "defective slco1b1 causes hyperbilirubinemia", "causes hyperbilirubinemia rotor", "hyperbilirubinemia rotor type", "rotor type hblrr", "slco1b1 causes hyperbilirubinemia rotor", "causes hyperbilirubinemia rotor type", "the solute", "solute carrier", "carrier organic", "organic anion", "anion transporter", "transporter family", "family member", "member 1b1", "is expressed", "expressed on", "on the", "the basolateral", "basolateral surfaces", "surfaces of", "of hepatocytes", "hepatocytes and", "and mediates", "mediates the", "the uptake", "uptake of", "of bilirubin", "a breakdown", "breakdown product", "product of", "of heme", "heme degradation", "to the", "the liver", "liver where", "where it", "it is", "is conjugated", "conjugated and", "and excreted", "excreted from", "from the", "the body.", "body. defects", "defects in", "in slco1b1", "slco1b1 can", "can cause", "cause hyperbilirubinemia", "an autosomal", "autosomal recessive", "recessive form", "form of", "of primary", "primary conjugated", "conjugated hyperbilirubinemia.", "hyperbilirubinemia. mild", "mild jaundice", "not associated", "associated with", "with hemolysis", "develops shortly", "shortly after", "after birth", "birth or", "or in", "in childhood", "van de", "de steeg", "steeg et", "et al.", "al. 2012", "sticova &", "& jirsa", "jirsa 2013", "keppler 2014", "2014 .", "the solute carrier", "solute carrier organic", "carrier organic anion", "organic anion transporter", "anion transporter family", "transporter family member", "family member 1b1", "1b1 slco1b1", "slco1b1 is", "is expressed on", "expressed on the", "on the basolateral", "the basolateral surfaces", "basolateral surfaces of", "surfaces of hepatocytes", "of hepatocytes and", "hepatocytes and mediates", "and mediates the", "mediates the uptake", "the uptake of", "uptake of bilirubin", "bilirubin bil", "a breakdown product", "breakdown product of", "product of heme", "of heme degradation", "degradation to", "to the liver", "the liver where", "liver where it", "where it is", "it is conjugated", "is conjugated and", "conjugated and excreted", "and excreted from", "excreted from the", "from the body.", "the body. defects", "body. defects in", "defects in slco1b1", "in slco1b1 can", "slco1b1 can cause", "can cause hyperbilirubinemia", "hblrr mim:237450", "an autosomal recessive", "autosomal recessive form", "recessive form of", "form of primary", "of primary conjugated", "primary conjugated hyperbilirubinemia.", "conjugated hyperbilirubinemia. mild", "hyperbilirubinemia. mild jaundice", "jaundice not", "not associated with", "associated with hemolysis", "hemolysis develops", "develops shortly after", "shortly after birth", "after birth or", "birth or in", "or in childhood", "childhood van", "van de steeg", "de steeg et", "steeg et al.", "et al. 2012", "2012 sticova", "sticova & jirsa", "& jirsa 2013", "2013 keppler", "keppler 2014 .", "the solute carrier organic", "solute carrier organic anion", "carrier organic anion transporter", "organic anion transporter family", "anion transporter family member", "transporter family member 1b1", "member 1b1 slco1b1", "slco1b1 is expressed", "is expressed on the", "expressed on the basolateral", "on the basolateral surfaces", "the basolateral surfaces of", "basolateral surfaces of hepatocytes", "surfaces of hepatocytes and", "of hepatocytes and mediates", "hepatocytes and mediates the", "and mediates the uptake", "mediates the uptake of", "the uptake of bilirubin", "of bilirubin bil", "bil a", "a breakdown product of", "breakdown product of heme", "product of heme degradation", "heme degradation to", "degradation to the", "to the liver where", "the liver where it", "liver where it is", "where it is conjugated", "it is conjugated and", "is conjugated and excreted", "conjugated and excreted from", "and excreted from the", "excreted from the body.", "from the body. defects", "the body. defects in", "body. defects in slco1b1", "defects in slco1b1 can", "in slco1b1 can cause", "slco1b1 can cause hyperbilirubinemia", "cause hyperbilirubinemia rotor", "mim:237450 an", "237450 an", "an autosomal recessive form", "autosomal recessive form of", "recessive form of primary", "form of primary conjugated", "of primary conjugated hyperbilirubinemia.", "primary conjugated hyperbilirubinemia. mild", "conjugated hyperbilirubinemia. mild jaundice", "mild jaundice not", "jaundice not associated", "not associated with hemolysis", "with hemolysis develops", "hemolysis develops shortly", "develops shortly after birth", "shortly after birth or", "after birth or in", "birth or in childhood", "in childhood van", "childhood van de", "van de steeg et", "de steeg et al.", "steeg et al. 2012", "al. 2012 sticova", "2012 sticova &", "sticova & jirsa 2013", "jirsa 2013 keppler", "2013 keppler 2014", "the solute carrier organic anion", "solute carrier organic anion transporter", "carrier organic anion transporter family", "organic anion transporter family member", "anion transporter family member 1b1", "family member 1b1 slco1b1", "1b1 slco1b1 is", "slco1b1 is expressed on", "is expressed on the basolateral", "expressed on the basolateral surfaces", "on the basolateral surfaces of", "the basolateral surfaces of hepatocytes", "basolateral surfaces of hepatocytes and", "surfaces of hepatocytes and mediates", "of hepatocytes and mediates the", "hepatocytes and mediates the uptake", "and mediates the uptake of", "mediates the uptake of bilirubin", "uptake of bilirubin bil", "bil a breakdown", "a breakdown product of heme", "breakdown product of heme degradation", "of heme degradation to", "heme degradation to the", "degradation to the liver", "to the liver where it", "the liver where it is", "liver where it is conjugated", "where it is conjugated and", "it is conjugated and excreted", "is conjugated and excreted from", "conjugated and excreted from the", "and excreted from the body.", "excreted from the body. defects", "from the body. defects in", "the body. defects in slco1b1", "body. defects in slco1b1 can", "defects in slco1b1 can cause", "in slco1b1 can cause hyperbilirubinemia", "can cause hyperbilirubinemia rotor", "cause hyperbilirubinemia rotor type", "type hblrr mim:237450", "mim:237450 an autosomal", "237450 an autosomal", "an autosomal recessive form of", "autosomal recessive form of primary", "recessive form of primary conjugated", "form of primary conjugated hyperbilirubinemia.", "of primary conjugated hyperbilirubinemia. mild", "primary conjugated hyperbilirubinemia. mild jaundice", "hyperbilirubinemia. mild jaundice not", "mild jaundice not associated", "jaundice not associated with", "associated with hemolysis develops", "with hemolysis develops shortly", "hemolysis develops shortly after", "develops shortly after birth or", "shortly after birth or in", "after birth or in childhood", "or in childhood van", "in childhood van de", "childhood van de steeg", "van de steeg et al.", "de steeg et al. 2012", "et al. 2012 sticova", "al. 2012 sticova &", "2012 sticova & jirsa", "& jirsa 2013 keppler", "jirsa 2013 keppler 2014", "2013 keppler 2014 ." ] }, { "record_id": "GLY_000594_1_1427", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5621480", "r hsa", "hsa 5621480", "r hsa 5621480" ] }, { "record_id": "GLY_000594_1_1427", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "dectin 2", "2 family", "dectin 2 family", "dendritic cell", "cell associated", "associated c", "c type", "type lectin", "lectin 2", "family of", "of c", "lectin receptors", "includes dectin", "blood dendritic", "dendritic antigen", "antigen 2", "macrophage c", "cell immunoreceptor", "and macrophage", "macrophage inducible", "inducible c", "mincle/clec4e .", ". these", "these receptors", "receptors possesses", "possesses a", "a single", "single extracellular", "extracellular conserved", "conserved c", "lectin domain", "with a", "a short", "short cytoplasmic", "cytoplasmic tail", "tail that", "that induces", "induces intracellular", "intracellular signalling", "signalling indirectly", "indirectly by", "by binding", "binding with", "with the", "the fcerg", "high affinity", "affinity immunoglobulin", "immunoglobulin epsilon", "epsilon receptor", "receptor subunit", "subunit gamma", "except for", "for dcir", "dcir that", "that has", "has a", "a longer", "longer cytoplasmic", "tail with", "with an", "an integral", "integral inhibitory", "inhibitory signalling", "signalling motif", "graham &", "& brown.", "brown. 2009", "kerschera et", "et al.", "al. 2013", "2013 .", ". clec6a", "binds to", "to high", "high mannose", "mannose containing", "containing pathogen", "pathogen associated", "associated molecular", "molecular patterns", "expressed by", "by fungal", "fungal hyphae", "and clec4e", "to alpha", "alpha mannaosyl", "mannaosyl pamps", "pamps on", "on fungal", "mycobacterial and", "and necrotic", "necrotic cell", "cell ligands.", "ligands. both", "both signaling", "signaling pathways", "pathways lead", "lead to", "to toll", "toll like", "like receptor", "independent production", "production of", "of cytokines", "cytokines such", "such as", "as tumor", "tumor necrosis", "necrosis factor", "and interleukin", "interleukin 6", "il6 .", ". similarities", "similarities with", "with dectin", "dectin 1", "signaling pathway", "pathway suggests", "suggests that", "that both", "both these", "these clrs", "clrs couple", "couple syk", "syk activation", "activation to", "to nf", "nf kb", "kb activation", "activation using", "using a", "a complex", "complex involving", "involving card9", "bcl10 and", "and malt1", "geijtenbeek &", "& gringhuis", "gringhuis 2009", "2009 .", "dendritic cell associated", "cell associated c", "associated c type", "c type lectin", "type lectin 2", "2 dectin", "family of c", "of c type", "type lectin receptors", "receptors clrs", "clrs includes", "includes dectin 2", "2 clec6a", "blood dendritic antigen", "dendritic antigen 2", "2 bdca2/clec4c", "macrophage c type", "lectin mcl/clec4d", "dendritic cell immunoreceptor", "immunoreceptor dcir/clec4a", "dcir/clec4a and", "and macrophage inducible", "macrophage inducible c", "inducible c type", "lectin mincle/clec4e", "mincle/clec4e . these", ". these receptors", "these receptors possesses", "receptors possesses a", "possesses a single", "a single extracellular", "single extracellular conserved", "extracellular conserved c", "conserved c type", "type lectin domain", "domain ctld", "ctld with", "with a short", "a short cytoplasmic", "short cytoplasmic tail", "cytoplasmic tail that", "tail that induces", "that induces intracellular", "induces intracellular signalling", "intracellular signalling indirectly", "signalling indirectly by", "indirectly by binding", "by binding with", "binding with the", "with the fcerg", "fcerg high", "high affinity immunoglobulin", "affinity immunoglobulin epsilon", "immunoglobulin epsilon receptor", "epsilon receptor subunit", "receptor subunit gamma", "gamma except", "except for dcir", "for dcir that", "dcir that has", "that has a", "has a longer", "a longer cytoplasmic", "longer cytoplasmic tail", "cytoplasmic tail with", "tail with an", "with an integral", "an integral inhibitory", "integral inhibitory signalling", "inhibitory signalling motif", "motif graham", "graham & brown.", "& brown. 2009", "2009 kerschera", "kerschera et al.", "et al. 2013", "al. 2013 .", "2013 . clec6a", "clec6a dectin", "2 binds", "binds to high", "to high mannose", "high mannose containing", "mannose containing pathogen", "containing pathogen associated", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "pamps expressed", "expressed by fungal", "by fungal hyphae", "hyphae and", "clec4e mincle", "mincle binds", "binds to alpha", "to alpha mannaosyl", "alpha mannaosyl pamps", "mannaosyl pamps on", "pamps on fungal", "fungal mycobacterial", "mycobacterial and necrotic", "and necrotic cell", "necrotic cell ligands.", "cell ligands. both", "ligands. both signaling", "both signaling pathways", "signaling pathways lead", "pathways lead to", "lead to toll", "to toll like", "toll like receptor", "receptor tlr", "tlr independent", "independent production of", "production of cytokines", "of cytokines such", "cytokines such as", "such as tumor", "as tumor necrosis", "tumor necrosis factor", "factor tnf", "tnf and", "and interleukin 6", "6 il6", "il6 . similarities", ". similarities with", "similarities with dectin", "with dectin 1", "1 clc7a", "clc7a signaling", "signaling pathway suggests", "pathway suggests that", "suggests that both", "that both these", "both these clrs", "these clrs couple", "clrs couple syk", "couple syk activation", "syk activation to", "activation to nf", "to nf kb", "nf kb activation", "kb activation using", "activation using a", "using a complex", "a complex involving", "complex involving card9", "card9 bcl10", "bcl10 and malt1", "malt1 geijtenbeek", "geijtenbeek & gringhuis", "& gringhuis 2009", "gringhuis 2009 .", "dendritic cell associated c", "cell associated c type", "associated c type lectin", "c type lectin 2", "lectin 2 dectin", "2 dectin 2", "2 family of", "family of c type", "of c type lectin", "c type lectin receptors", "lectin receptors clrs", "clrs includes dectin", "dectin 2 clec6a", "clec6a blood", "blood dendritic antigen 2", "antigen 2 bdca2/clec4c", "bdca2/clec4c macrophage", "macrophage c type lectin", "type lectin mcl/clec4d", "mcl/clec4d dendritic", "cell immunoreceptor dcir/clec4a", "dcir/clec4a and macrophage", "and macrophage inducible c", "macrophage inducible c type", "inducible c type lectin", "type lectin mincle/clec4e", "lectin mincle/clec4e .", "mincle/clec4e . these receptors", ". these receptors possesses", "these receptors possesses a", "receptors possesses a single", "possesses a single extracellular", "a single extracellular conserved", "single extracellular conserved c", "extracellular conserved c type", "conserved c type lectin", "c type lectin domain", "lectin domain ctld", "ctld with a", "with a short cytoplasmic", "a short cytoplasmic tail", "short cytoplasmic tail that", "cytoplasmic tail that induces", "tail that induces intracellular", "that induces intracellular signalling", "induces intracellular signalling indirectly", "intracellular signalling indirectly by", "signalling indirectly by binding", "indirectly by binding with", "by binding with the", "binding with the fcerg", "the fcerg high", "fcerg high affinity", "high affinity immunoglobulin epsilon", "affinity immunoglobulin epsilon receptor", "immunoglobulin epsilon receptor subunit", "epsilon receptor subunit gamma", "subunit gamma except", "gamma except for", "except for dcir that", "for dcir that has", "dcir that has a", "that has a longer", "has a longer cytoplasmic", "a longer cytoplasmic tail", "longer cytoplasmic tail with", "cytoplasmic tail with an", "tail with an integral", "with an integral inhibitory", "an integral inhibitory signalling", "integral inhibitory signalling motif", "signalling motif graham", "motif graham &", "graham & brown. 2009", "brown. 2009 kerschera", "2009 kerschera et", "kerschera et al. 2013", "et al. 2013 .", "al. 2013 . clec6a", ". clec6a dectin", "clec6a dectin 2", "dectin 2 binds", "2 binds to", "binds to high mannose", "to high mannose containing", "high mannose containing pathogen", "mannose containing pathogen associated", "containing pathogen associated molecular", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps expressed by", "expressed by fungal hyphae", "fungal hyphae and", "hyphae and clec4e", "and clec4e mincle", "mincle binds to", "binds to alpha mannaosyl", "to alpha mannaosyl pamps", "alpha mannaosyl pamps on", "mannaosyl pamps on fungal", "on fungal mycobacterial", "fungal mycobacterial and", "mycobacterial and necrotic cell", "and necrotic cell ligands.", "necrotic cell ligands. both", "cell ligands. both signaling", "ligands. both signaling pathways", "both signaling pathways lead", "signaling pathways lead to", "pathways lead to toll", "lead to toll like", "to toll like receptor", "like receptor tlr", "tlr independent production", "independent production of cytokines", "production of cytokines such", "of cytokines such as", "cytokines such as tumor", "such as tumor necrosis", "as tumor necrosis factor", "necrosis factor tnf", "tnf and interleukin", "interleukin 6 il6", "6 il6 .", "il6 . similarities with", ". similarities with dectin", "similarities with dectin 1", "dectin 1 clc7a", "clc7a signaling pathway", "signaling pathway suggests that", "pathway suggests that both", "suggests that both these", "that both these clrs", "both these clrs couple", "these clrs couple syk", "clrs couple syk activation", "couple syk activation to", "syk activation to nf", "activation to nf kb", "to nf kb activation", "nf kb activation using", "kb activation using a", "activation using a complex", "using a complex involving", "a complex involving card9", "involving card9 bcl10", "card9 bcl10 and", "and malt1 geijtenbeek", "malt1 geijtenbeek &", "geijtenbeek & gringhuis 2009", "& gringhuis 2009 .", "dendritic cell associated c type", "cell associated c type lectin", "associated c type lectin 2", "type lectin 2 dectin", "lectin 2 dectin 2", "dectin 2 family of", "2 family of c", "family of c type lectin", "of c type lectin receptors", "type lectin receptors clrs", "receptors clrs includes", "clrs includes dectin 2", "includes dectin 2 clec6a", "clec6a blood dendritic", "dendritic antigen 2 bdca2/clec4c", "bdca2/clec4c macrophage c", "c type lectin mcl/clec4d", "mcl/clec4d dendritic cell", "dendritic cell immunoreceptor dcir/clec4a", "immunoreceptor dcir/clec4a and", "dcir/clec4a and macrophage inducible", "and macrophage inducible c type", "macrophage inducible c type lectin", "c type lectin mincle/clec4e", "type lectin mincle/clec4e .", "lectin mincle/clec4e . these", "mincle/clec4e . these receptors possesses", ". these receptors possesses a", "these receptors possesses a single", "receptors possesses a single extracellular", "possesses a single extracellular conserved", "a single extracellular conserved c", "single extracellular conserved c type", "extracellular conserved c type lectin", "conserved c type lectin domain", "type lectin domain ctld", "domain ctld with", "ctld with a short", "with a short cytoplasmic tail", "a short cytoplasmic tail that", "short cytoplasmic tail that induces", "cytoplasmic tail that induces intracellular", "tail that induces intracellular signalling", "that induces intracellular signalling indirectly", "induces intracellular signalling indirectly by", "intracellular signalling indirectly by binding", "signalling indirectly by binding with", "indirectly by binding with the", "by binding with the fcerg", "with the fcerg high", "the fcerg high affinity", "fcerg high affinity immunoglobulin", "high affinity immunoglobulin epsilon receptor", "affinity immunoglobulin epsilon receptor subunit", "immunoglobulin epsilon receptor subunit gamma", "receptor subunit gamma except", "subunit gamma except for", "gamma except for dcir", "except for dcir that has", "for dcir that has a", "dcir that has a longer", "that has a longer cytoplasmic", "has a longer cytoplasmic tail", "a longer cytoplasmic tail with", "longer cytoplasmic tail with an", "cytoplasmic tail with an integral", "tail with an integral inhibitory", "with an integral inhibitory signalling", "an integral inhibitory signalling motif", "inhibitory signalling motif graham", "signalling motif graham &", "motif graham & brown.", "& brown. 2009 kerschera", "brown. 2009 kerschera et", "2009 kerschera et al.", "kerschera et al. 2013 .", "et al. 2013 . clec6a", "2013 . clec6a dectin", ". clec6a dectin 2", "dectin 2 binds to", "2 binds to high", "binds to high mannose containing", "to high mannose containing pathogen", "high mannose containing pathogen associated", "mannose containing pathogen associated molecular", "containing pathogen associated molecular patterns", "associated molecular patterns pamps", "patterns pamps expressed", "pamps expressed by fungal", "by fungal hyphae and", "fungal hyphae and clec4e", "clec4e mincle binds", "mincle binds to alpha", "binds to alpha mannaosyl pamps", "to alpha mannaosyl pamps on", "alpha mannaosyl pamps on fungal", "pamps on fungal mycobacterial", "on fungal mycobacterial and", "fungal mycobacterial and necrotic", "mycobacterial and necrotic cell ligands.", "and necrotic cell ligands. both", "necrotic cell ligands. both signaling", "cell ligands. both signaling pathways", "ligands. both signaling pathways lead", "both signaling pathways lead to", "signaling pathways lead to toll", "pathways lead to toll like", "lead to toll like receptor", "toll like receptor tlr", "receptor tlr independent", "tlr independent production of", "independent production of cytokines such", "production of cytokines such as", "of cytokines such as tumor", "cytokines such as tumor necrosis", "such as tumor necrosis factor", "tumor necrosis factor tnf", "factor tnf and", "tnf and interleukin 6", "and interleukin 6 il6", "interleukin 6 il6 .", "6 il6 . similarities", "il6 . similarities with dectin", ". similarities with dectin 1", "with dectin 1 clc7a", "1 clc7a signaling", "clc7a signaling pathway suggests", "signaling pathway suggests that both", "pathway suggests that both these", "suggests that both these clrs", "that both these clrs couple", "both these clrs couple syk", "these clrs couple syk activation", "clrs couple syk activation to", "couple syk activation to nf", "syk activation to nf kb", "activation to nf kb activation", "to nf kb activation using", "nf kb activation using a", "kb activation using a complex", "activation using a complex involving", "using a complex involving card9", "complex involving card9 bcl10", "involving card9 bcl10 and", "card9 bcl10 and malt1", "bcl10 and malt1 geijtenbeek", "and malt1 geijtenbeek &", "malt1 geijtenbeek & gringhuis", "geijtenbeek & gringhuis 2009 ." ] }, { "record_id": "GLY_000594_1_1428", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5627083", "r hsa", "hsa 5627083", "r hsa 5627083" ] }, { "record_id": "GLY_000594_1_1428", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases regulate", "regulate cftr", "cftr trafficking", "rho gtpases regulate", "gtpases regulate cftr", "regulate cftr trafficking", "rho gtpases regulate cftr", "gtpases regulate cftr trafficking", "rho gtpases regulate cftr trafficking", "activated rho", "rho gtpase", "gtpase rhoq", "regulates the", "the trafficking", "trafficking of", "of cftr", "cystic fibrosis", "fibrosis transmembrane", "transmembrane conductance", "conductance regulator", "by binding", "binding to", "to gopc", "golgi associated", "associated and", "and pdz", "pdz and", "and coiled", "coiled coil", "coil motif", "motif containing", "containing protein", "also known", "known as", "as pist", "fig or", "or cal.", "cal. gopc", "gopc is", "is a", "a golgi", "golgi resident", "resident protein", "protein that", "that binds", "binds several", "several membrane", "membrane proteins", "thereby modulating", "modulating their", "their expression.", "expression. in", "in the", "the absence", "absence of", "of rhoq", "gopc bound", "bound to", "to cftr", "cftr directs", "directs cftr", "cftr for", "for lysosomal", "lysosomal degradation", "while gtp", "gtp bound", "bound rhoq", "rhoq directs", "directs gopc:cftr", "gopc:cftr complex", "complex to", "to the", "the plasma", "plasma membrane", "thereby rescuing", "rescuing cftr", "neudauer et", "et al.", "al. 2001", "cheng et", "al. 2005", "2005 .", "activated rho gtpase", "rho gtpase rhoq", "rhoq tc10", "tc10 regulates", "regulates the trafficking", "the trafficking of", "trafficking of cftr", "cftr cystic", "cystic fibrosis transmembrane", "fibrosis transmembrane conductance", "transmembrane conductance regulator", "regulator by", "by binding to", "binding to gopc", "gopc golgi", "golgi associated and", "associated and pdz", "and pdz and", "pdz and coiled", "and coiled coil", "coiled coil motif", "coil motif containing", "motif containing protein", "protein also", "also known as", "known as pist", "pist fig", "fig or cal.", "or cal. gopc", "cal. gopc is", "gopc is a", "is a golgi", "a golgi resident", "golgi resident protein", "resident protein that", "protein that binds", "that binds several", "binds several membrane", "several membrane proteins", "proteins thereby", "thereby modulating their", "modulating their expression.", "their expression. in", "expression. in the", "in the absence", "the absence of", "absence of rhoq", "rhoq gopc", "gopc bound to", "bound to cftr", "to cftr directs", "cftr directs cftr", "directs cftr for", "cftr for lysosomal", "for lysosomal degradation", "degradation while", "while gtp bound", "gtp bound rhoq", "bound rhoq directs", "rhoq directs gopc:cftr", "directs gopc:cftr complex", "gopc:cftr complex to", "complex to the", "to the plasma", "the plasma membrane", "membrane thereby", "thereby rescuing cftr", "cftr neudauer", "neudauer et al.", "et al. 2001", "2001 cheng", "cheng et al.", "et al. 2005", "al. 2005 .", "activated rho gtpase rhoq", "gtpase rhoq tc10", "tc10 regulates the", "regulates the trafficking of", "the trafficking of cftr", "of cftr cystic", "cftr cystic fibrosis", "cystic fibrosis transmembrane conductance", "fibrosis transmembrane conductance regulator", "conductance regulator by", "regulator by binding", "by binding to gopc", "to gopc golgi", "gopc golgi associated", "golgi associated and pdz", "associated and pdz and", "and pdz and coiled", "pdz and coiled coil", "and coiled coil motif", "coiled coil motif containing", "coil motif containing protein", "containing protein also", "protein also known", "also known as pist", "as pist fig", "pist fig or", "fig or cal. gopc", "or cal. gopc is", "cal. gopc is a", "gopc is a golgi", "is a golgi resident", "a golgi resident protein", "golgi resident protein that", "resident protein that binds", "protein that binds several", "that binds several membrane", "binds several membrane proteins", "membrane proteins thereby", "proteins thereby modulating", "thereby modulating their expression.", "modulating their expression. in", "their expression. in the", "expression. in the absence", "in the absence of", "the absence of rhoq", "of rhoq gopc", "rhoq gopc bound", "gopc bound to cftr", "bound to cftr directs", "to cftr directs cftr", "cftr directs cftr for", "directs cftr for lysosomal", "cftr for lysosomal degradation", "lysosomal degradation while", "degradation while gtp", "while gtp bound rhoq", "gtp bound rhoq directs", "bound rhoq directs gopc:cftr", "rhoq directs gopc:cftr complex", "directs gopc:cftr complex to", "gopc:cftr complex to the", "complex to the plasma", "to the plasma membrane", "plasma membrane thereby", "membrane thereby rescuing", "rescuing cftr neudauer", "cftr neudauer et", "neudauer et al. 2001", "al. 2001 cheng", "2001 cheng et", "cheng et al. 2005", "et al. 2005 .", "rho gtpase rhoq tc10", "rhoq tc10 regulates", "tc10 regulates the trafficking", "regulates the trafficking of cftr", "trafficking of cftr cystic", "of cftr cystic fibrosis", "cftr cystic fibrosis transmembrane", "cystic fibrosis transmembrane conductance regulator", "transmembrane conductance regulator by", "conductance regulator by binding", "regulator by binding to", "binding to gopc golgi", "to gopc golgi associated", "gopc golgi associated and", "golgi associated and pdz and", "associated and pdz and coiled", "and pdz and coiled coil", "pdz and coiled coil motif", "and coiled coil motif containing", "coiled coil motif containing protein", "motif containing protein also", "containing protein also known", "protein also known as", "known as pist fig", "as pist fig or", "pist fig or cal.", "fig or cal. gopc is", "or cal. gopc is a", "cal. gopc is a golgi", "gopc is a golgi resident", "is a golgi resident protein", "a golgi resident protein that", "golgi resident protein that binds", "resident protein that binds several", "protein that binds several membrane", "that binds several membrane proteins", "several membrane proteins thereby", "membrane proteins thereby modulating", "proteins thereby modulating their", "thereby modulating their expression. in", "modulating their expression. in the", "their expression. in the absence", "expression. in the absence of", "in the absence of rhoq", "absence of rhoq gopc", "of rhoq gopc bound", "rhoq gopc bound to", "gopc bound to cftr directs", "bound to cftr directs cftr", "to cftr directs cftr for", "cftr directs cftr for lysosomal", "directs cftr for lysosomal degradation", "for lysosomal degradation while", "lysosomal degradation while gtp", "degradation while gtp bound", "while gtp bound rhoq directs", "gtp bound rhoq directs gopc:cftr", "bound rhoq directs gopc:cftr complex", "rhoq directs gopc:cftr complex to", "directs gopc:cftr complex to the", "gopc:cftr complex to the plasma", "complex to the plasma membrane", "the plasma membrane thereby", "plasma membrane thereby rescuing", "membrane thereby rescuing cftr", "thereby rescuing cftr neudauer", "rescuing cftr neudauer et", "cftr neudauer et al.", "et al. 2001 cheng", "al. 2001 cheng et", "2001 cheng et al.", "cheng et al. 2005 ." ] }, { "record_id": "GLY_000594_1_1429", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5632927", "r hsa", "hsa 5632927", "r hsa 5632927" ] }, { "record_id": "GLY_000594_1_1429", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective mismatch", "mismatch repair", "repair associated", "associated with", "with msh3", "defective mismatch repair", "mismatch repair associated", "repair associated with", "associated with msh3", "defective mismatch repair associated", "mismatch repair associated with", "repair associated with msh3", "defective mismatch repair associated with", "mismatch repair associated with msh3", "msh3 forms", "forms a", "a heterodimer", "heterodimer with", "with msh2", "msh2 to", "to form", "form the", "the msh3:msh2", "msh3:msh2 complex", "part of", "of the", "the post", "post replicative", "replicative dna", "dna mismatch", "repair system.", 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gene contains", "this gene contains a", "gene contains a polymorphic", "contains a polymorphic 9", "a polymorphic 9 bp", "polymorphic 9 bp tandem", "9 bp tandem repeat", "bp tandem repeat sequence", "tandem repeat sequence in", "repeat sequence in the", "sequence in the first", "in the first exon.", "the first exon. defects", "first exon. defects in", "exon. defects in this", "defects in this gene", "in this gene are", "this gene are a", "gene are a cause", "are a cause of", "a cause of susceptibility", "cause of susceptibility to", "of susceptibility to endometrial", "susceptibility to endometrial cancer.", "msh3 forms a heterodimer with", "forms a heterodimer with msh2", "a heterodimer with msh2 to", "heterodimer with msh2 to form", "with msh2 to form the", "msh2 to form the msh3:msh2", "to form the msh3:msh2 complex", "the msh3:msh2 complex part", "msh3:msh2 complex part of", "complex part of the", "part of the post replicative", "of the post replicative dna", "the post replicative dna mismatch", "post replicative dna mismatch repair", "replicative dna mismatch repair system.", "dna mismatch repair system. this", "mismatch repair system. this complex", "repair system. this complex initiates", "system. this complex initiates mismatch", "this complex initiates mismatch repair", "complex initiates mismatch repair by", "initiates mismatch repair by binding", "mismatch repair by binding to", "repair by binding to a", "by binding to a mismatch", "binding to a mismatch and", "to a mismatch and then", "a mismatch and then forming", "mismatch and then forming a", "and then forming a complex", "then forming a complex with", "forming a complex with mutl", "a complex with mutl alpha", "complex with mutl alpha heterodimer.", "with mutl alpha heterodimer. this", "mutl alpha heterodimer. this gene", "alpha heterodimer. this gene contains", "heterodimer. this gene contains a", "this gene contains a polymorphic", "gene contains a polymorphic 9", "contains a polymorphic 9 bp", "a polymorphic 9 bp tandem", "polymorphic 9 bp tandem repeat", "9 bp tandem repeat sequence", "bp tandem repeat sequence in", "tandem repeat sequence in the", "repeat sequence in the first", "sequence in the first exon.", "in the first exon. defects", "the first exon. defects in", "first exon. defects in this", "exon. defects in this gene", "defects in this gene are", "in this gene are a", "this gene are a cause", "gene are a cause of", "are a cause of susceptibility", "a cause of susceptibility to", "cause of susceptibility to endometrial", "of susceptibility to endometrial cancer." ] }, { "record_id": "GLY_000594_1_1430", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5632928", "r hsa", "hsa 5632928", "r hsa 5632928" ] }, { "record_id": "GLY_000594_1_1430", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective mismatch", "mismatch repair", "repair associated", "associated with", "with msh2", "defective mismatch repair", "mismatch repair associated", "repair associated with", "associated with msh2", "defective mismatch repair associated", "mismatch repair associated with", "repair associated with msh2", "defective mismatch repair associated with", "mismatch repair associated with msh2", "msh2 is", "is homologous", "homologous to", "to the", "the e.", "e. coli", "coli muts", "muts gene", "gene and", "and is", "is involved", "involved in", "in dna", "dna mismatch", "fishel et", "et al.", "1994 .", ". heterozygous", "heterozygous mutations", "mutations in", "in the", "the msh2", "msh2 gene", "gene result", "result in", "in hereditary", "hereditary nonpolyposis", "nonpolyposis colorectal", "colorectal cancer", "cancer 1.", "1. variants", "variants of", "of msh2", "msh2 are", "are associated", "with hereditary", "colorectal cancer.", "cancer. alteration", "alteration of", "is also", "also involved", "in muir", "muir torre", "torre syndrome", "syndrome and", "and 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"ber may occur", "may occur in", "occur in cells", "in cells in", "cells in the", "in the s", "the s phase", "s phase of", "phase of the", "of the cell", "the cell cycle", "cycle when", "when the replication", "the replication complexes", "replication complexes that", "complexes that contain", "that contain pcna", "pcna pold", "pold or pole", "pole rpa", "rpa and rfc", "and rfc are", "rfc are available.", "are available. polb", "available. polb incorporates", "polb incorporates the", "incorporates the first", "the first nucleotide", "first nucleotide at", "nucleotide at the", "at the 3'", "the 3' end", "3' end of", "end of apex1", "of apex1 generated", "apex1 generated single", "generated single strand", "single strand break", "break ssb", "thus displacing the", "displacing the damaged", "the damaged ap", "ap abasic", "abasic dideoxyribose", "dideoxyribose phosphate residue", "phosphate residue at", "residue at the", "at the 5'", "the 5' end", "5' end of", "end of ssb", "ssb 5'ddrp", 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"patch at the", "end of the", "of the ssb", "the ssb with", "ssb with the", "with the fen1", "the fen1 processed", "fen1 processed 5'", "processed 5' end", "ssb klungland", "klungland and lindahl", "and lindahl 1997", "1997 stucki", "stucki et al.", "et al. 1998", "1998 dianov", "dianov et al.", "et al. 1999", "1999 matsumoto", "matsumoto et al.", "1999 podlutsky", "podlutsky et al.", "et al. 2001", "2001 dianova", "dianova et al.", "2001 ranalli", "ranalli et al.", "et al. 2002", "al. 2002 .", "excision repair ber", "ber can proceed", "can proceed through pcna", "proceed through pcna dependent", "through pcna dependent dna", "pcna dependent dna strand", "dependent dna strand displacement", "dna strand displacement synthesis", "strand displacement synthesis by", "displacement synthesis by replicative", "synthesis by replicative dna", "by replicative dna polymerases", "polymerases dna", "dna polymerase delta complex", "delta complex pold", "pold or dna", "or dna polymerase epsilon", "polymerase epsilon pole", "pole complex. the", "complex. the pcna dependent", "the pcna dependent branch", "pcna dependent branch of", "dependent branch of long", "branch of long patch", "of long patch ber", "long patch ber may", "patch ber may occur", "ber may occur in", "may occur in cells", "occur in cells in", "in cells in the", "cells in the s", "in the s phase", "the s phase of", "s phase of the", "phase of the cell", "of the cell cycle", "cell cycle when", "cycle when the", "when the replication complexes", "the replication complexes that", "replication complexes that contain", "complexes that contain pcna", "contain pcna pold", "pcna pold or", "or pole rpa", "pole rpa and", "rpa and rfc are", "and rfc are available.", "rfc are available. polb", "are available. polb incorporates", "available. polb incorporates the", "polb incorporates the first", "incorporates the first nucleotide", "the first nucleotide at", "first nucleotide at the", "nucleotide at the 3'", "at the 3' end", "the 3' end of", "3' end of apex1", "end of apex1 generated", "of apex1 generated single", "apex1 generated single strand", "generated single strand break", "strand break ssb", "ssb thus", "thus displacing the damaged", "displacing the damaged ap", "damaged ap abasic", "abasic dideoxyribose phosphate", "dideoxyribose phosphate residue at", "phosphate residue at the", "residue at the 5'", "at the 5' end", "the 5' end of", "5' end of ssb", "of ssb 5'ddrp", "ssb 5'ddrp .", "5'ddrp . pcna is", ". pcna is recruited", "pcna is recruited to", "is recruited to ber", "recruited to ber sites", "to ber sites by", "ber sites by apex1", "sites by apex1 and", "by apex1 and flap", "apex1 and flap endonuclease", "and flap endonuclease fen1", "endonuclease fen1 and", "fen1 and loaded", "and loaded onto damaged", "loaded onto damaged dna", "onto damaged dna by", "damaged dna by rfc.", "dna by rfc. pold", "by rfc. pold and", "rfc. pold and pole", "pold and pole in", "and pole in complex", "pole in complex with", "in complex with pcna", "complex with pcna continue", "with pcna continue the", "pcna continue the displacement", "continue the displacement dna", "the displacement dna strand", "displacement dna strand synthesis.", "dna strand synthesis. fen1", "strand synthesis. fen1 cleaves", "synthesis. fen1 cleaves the", "fen1 cleaves the displaced", "cleaves the displaced dna", "the displaced dna strand", "displaced dna strand with", "dna strand with the", "strand with the ap", "with the ap residue", "ap residue 5'ddrp", "5'ddrp and", "and dna ligase i", "ligase i lig1", "lig1 ligates the", "ligates the multiple nucleotide", "the multiple nucleotide patch", "multiple nucleotide patch at", "nucleotide patch at the", "patch at the 3'", "3' end of the", "end of the ssb", "of the ssb with", "the ssb with the", "ssb with the fen1", "with the fen1 processed", "the fen1 processed 5'", "fen1 processed 5' end", "processed 5' end of", "5' end of the", "the ssb klungland", "ssb klungland and", "klungland and lindahl 1997", "lindahl 1997 stucki", "1997 stucki et", "stucki et al. 1998", "al. 1998 dianov", "1998 dianov et", "dianov et al. 1999", "al. 1999 matsumoto", "1999 matsumoto et", "matsumoto et al. 1999", "al. 1999 podlutsky", "1999 podlutsky et", "podlutsky et al. 2001", "al. 2001 dianova", "2001 dianova et", "dianova et al. 2001", "al. 2001 ranalli", "2001 ranalli et", "ranalli et al. 2002", "et al. 2002 .", "base excision repair ber", "repair ber can", "ber can proceed through", "can proceed through pcna dependent", "proceed through pcna dependent dna", "through pcna dependent dna strand", "pcna dependent dna strand displacement", "dependent dna strand displacement synthesis", "dna strand displacement synthesis by", "strand displacement synthesis by replicative", "displacement synthesis by replicative dna", "synthesis by replicative dna polymerases", "dna polymerases dna", "polymerases dna polymerase", "polymerase delta complex pold", "complex pold or", "pold or dna polymerase", "dna polymerase epsilon pole", "epsilon pole complex.", "pole complex. the pcna", "complex. the pcna dependent branch", "the pcna dependent branch of", "pcna dependent branch of long", "dependent branch of long patch", "branch of long patch ber", "of long patch ber may", "long patch ber may occur", "patch ber may occur in", "ber may occur in cells", "may occur in cells in", "occur in cells in the", "in cells in the s", "cells in the s phase", "in the s phase of", "the s phase of the", "s phase of the cell", "phase of the cell cycle", "the cell cycle when", "cell cycle when the", "cycle when the replication", "when the replication complexes that", "the replication complexes that contain", "replication complexes that contain pcna", "that contain pcna pold", "contain pcna pold or", "pcna pold or pole", "pold or pole rpa", "or pole rpa and", "pole rpa and rfc", "rpa and rfc are available.", "and rfc are available. polb", "rfc are available. polb incorporates", "are available. polb incorporates the", "available. polb incorporates the first", "polb incorporates the first nucleotide", "incorporates the first nucleotide at", "the first nucleotide at the", "first nucleotide at the 3'", "nucleotide at the 3' end", "at the 3' end of", "the 3' end of apex1", "3' end of apex1 generated", "end of apex1 generated single", "of apex1 generated single strand", "apex1 generated single strand break", "single strand break ssb", "ssb thus displacing", "thus displacing the damaged ap", "the damaged ap abasic", "ap abasic dideoxyribose", "abasic dideoxyribose phosphate residue", "dideoxyribose phosphate residue at the", "phosphate residue at the 5'", "residue at the 5' end", "at the 5' end of", "the 5' end of ssb", "end of ssb 5'ddrp", "of ssb 5'ddrp .", "ssb 5'ddrp . pcna", "5'ddrp . pcna is recruited", ". pcna is recruited to", "pcna is recruited to ber", "is recruited to ber sites", "recruited to ber sites by", "to ber sites by apex1", "ber sites by apex1 and", "sites by apex1 and flap", "by apex1 and flap endonuclease", "apex1 and flap endonuclease fen1", "flap endonuclease fen1 and", "endonuclease fen1 and loaded", "fen1 and loaded onto", "and loaded onto damaged dna", "loaded onto damaged dna by", "onto damaged dna by rfc.", "damaged dna by rfc. pold", "dna by rfc. pold and", "by rfc. pold and pole", "rfc. pold and pole in", "pold and pole in complex", "and pole in complex with", "pole in complex with pcna", "in complex with pcna continue", "complex with pcna continue the", "with pcna continue the displacement", "pcna continue the displacement dna", "continue the displacement dna strand", "the displacement dna strand synthesis.", "displacement dna strand synthesis. fen1", "dna strand synthesis. fen1 cleaves", "strand synthesis. fen1 cleaves the", "synthesis. fen1 cleaves the displaced", "fen1 cleaves the displaced dna", "cleaves the displaced dna strand", "the displaced dna strand with", "displaced dna strand with the", "dna strand with the ap", "strand with the ap residue", "the ap residue 5'ddrp", "5'ddrp and dna", "dna ligase i lig1", "i lig1 ligates", "lig1 ligates the multiple", "ligates the multiple nucleotide patch", "the multiple nucleotide patch at", "multiple nucleotide patch at the", "nucleotide patch at the 3'", "patch at the 3' end", "the 3' end of the", "3' end of the ssb", "end of the ssb with", "of the ssb with the", "the ssb with the fen1", "ssb with the fen1 processed", "with the fen1 processed 5'", "the fen1 processed 5' end", "fen1 processed 5' end of", "processed 5' end of the", "5' end of the ssb", "of the ssb klungland", "the ssb klungland and", "ssb klungland and lindahl", "and lindahl 1997 stucki", "lindahl 1997 stucki et", "1997 stucki et al.", "et al. 1998 dianov", "al. 1998 dianov et", "1998 dianov et al.", "et al. 1999 matsumoto", "al. 1999 matsumoto et", "1999 matsumoto et al.", "et al. 1999 podlutsky", "al. 1999 podlutsky et", "1999 podlutsky et al.", "et al. 2001 dianova", "al. 2001 dianova et", "2001 dianova et al.", "et al. 2001 ranalli", "al. 2001 ranalli et", "2001 ranalli et al.", "ranalli et al. 2002 ." ] }, { "record_id": "GLY_000594_1_1433", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5652227", "r hsa", "hsa 5652227", "r hsa 5652227" ] }, { "record_id": "GLY_000594_1_1433", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fructose biosynthesis", "the conversion", "conversion of", "of glucose", "glucose to", "to fructose", "fructose via", "via sorbitol", "sorbitol was", "was demonstrated", "demonstrated by", "by hers", "in the", "the seminal", "seminal vesicles", "vesicles of", "of sheep", "has since", "since been", "been demonstrated", "demonstrated as", "as well", "well in", "in human", "human epidydimal", "epidydimal tissue", "frenette et", "et al.", "al. 2006", "and appears", "appears to", "to be", "be the", "the physiological", "physiological source", "source of", "of the", "the abundant", "abundant fructose", "fructose found", "found in", "in seminal", "seminal fluid.", "fluid. the", "the enzymes", "enzymes of", "the pathway", "pathway are", "are likewise", "likewise abundant", "abundant in", "the eye", "eye lens", "lens and", "and in", "in neurons", "where their", "their physiological", "physiological role", "role is", "is less", "less clear", "clear but", "but where", "where they", "they appear", "appear to", "to play", "play a", "a central", "central role", "role in", "in diabetic", "diabetic tissue", "tissue damage", "oates 2008", "2008 .", "the conversion of", "conversion of glucose", "of glucose to", "glucose to fructose", "to fructose via", "fructose via sorbitol", "via sorbitol was", "sorbitol was demonstrated", "was demonstrated by", "demonstrated by hers", "hers 1960", "1960 in", "in the seminal", "the seminal vesicles", "seminal vesicles of", "vesicles of sheep", "sheep has", "has since been", "since been demonstrated", 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a", "play a central", "a central role", "central role in", "role in diabetic", "in diabetic tissue", "diabetic tissue damage", "damage oates", "oates 2008 .", "the conversion of glucose", "conversion of glucose to", "of glucose to fructose", "glucose to fructose via", "to fructose via sorbitol", "fructose via sorbitol was", "via sorbitol was demonstrated", "sorbitol was demonstrated by", "was demonstrated by hers", "by hers 1960", "1960 in the", "in the seminal vesicles", "the seminal vesicles of", "seminal vesicles of sheep", "of sheep has", "sheep has since", "has since been demonstrated", "since been demonstrated as", "been demonstrated as well", "demonstrated as well in", "as well in human", "well in human epidydimal", "in human epidydimal tissue", "epidydimal tissue frenette", "tissue frenette et", "frenette et al. 2006", "2006 and", "and appears to be", "appears to be the", "to be the physiological", "be the physiological source", "the physiological source of", "physiological 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"in diabetic tissue damage", "tissue damage oates", "damage oates 2008", "the conversion of glucose to", "conversion of glucose to fructose", "of glucose to fructose via", "glucose to fructose via sorbitol", "to fructose via sorbitol was", "fructose via sorbitol was demonstrated", "via sorbitol was demonstrated by", "sorbitol was demonstrated by hers", "demonstrated by hers 1960", "hers 1960 in", "1960 in the seminal", "in the seminal vesicles of", "the seminal vesicles of sheep", "vesicles of sheep has", "of sheep has since", "sheep has since been", "has since been demonstrated as", "since been demonstrated as well", "been demonstrated as well in", "demonstrated as well in human", "as well in human epidydimal", "well in human epidydimal tissue", "human epidydimal tissue frenette", "epidydimal tissue frenette et", "tissue frenette et al.", "al. 2006 and", "2006 and appears", "and appears to be the", "appears to be the physiological", "to be the physiological source", "be the physiological source of", "the physiological source of the", "physiological source of the abundant", "source of the abundant fructose", "of the abundant fructose found", "the abundant fructose found in", "abundant fructose found in seminal", "fructose found in seminal fluid.", "found in seminal fluid. the", "in seminal fluid. the enzymes", "seminal fluid. the enzymes of", "fluid. the enzymes of the", "the enzymes of the pathway", "enzymes of the pathway are", "of the pathway are likewise", "the pathway are likewise abundant", "pathway are likewise abundant in", "are likewise abundant in the", "likewise abundant in the eye", "abundant in the eye lens", "in the eye lens and", "the eye lens and in", "eye lens and in neurons", "and in neurons where", "in neurons where their", "neurons where their physiological", "where their physiological role is", "their physiological role is less", "physiological role is less clear", "role is less clear but", "is less clear but where", "less clear but 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"defective slc5a1 causes congenital", "slc5a1 causes congenital glucose/galactose", "causes congenital glucose/galactose malabsorption", "glucose/galactose malabsorption ggm", "defective slc5a1 causes congenital glucose/galactose", "slc5a1 causes congenital glucose/galactose malabsorption", "congenital glucose/galactose malabsorption ggm", "sodium/glucose cotransporter", "cotransporter 1", "slc5a1 aka", "aka sglt1", "actively and", "and reversibly", "reversibly transports", "transports glucose", "into cells", "cells by", "by na+", "na+ cotransport", "cotransport with", "with a", "a na+", "na+ to", "to glucose", "glucose coupling", "coupling ratio", "ratio of", "of 2:1.", "2:1. slc5a1", "slc5a1 is", "is mainly", "mainly expressed", "expressed in", "in the", "the microvilli", "microvilli of", "of intestine", "intestine and", "and kidney", "kidney and", "and responsible", "responsible for", "for the", "the absorption", "absorption of", "of sugars.", "sugars. overexpressed", "overexpressed slc5a1", "slc5a1 has", "has been", "been found", "found in", "in various", "various cancers", "possibly playing", "playing a", "a role", "role in", "in preventing", "preventing autophagic", "autophagic cell", "cell death", "death by", "by maintaining", "maintaining intracellular", "intracellular glucose", "glucose levels.", "levels. defects", "defects in", "in slc5a1", "slc5a1 can", "can cause", "cause congenital", "an autosomal", "autosomal recessive", "recessive disorder", "disorder manifesting", "manifesting itself", "itself in", "in newborns", "newborns characterised", "characterised by", "by severe", "life threatening", "threatening diarrhea", "diarrhea which", "which is", "is usually", "usually fatal", "fatal unless", "unless glucose", "glucose and", "and galactose", "galactose are", "are removed", "removed from", "from the", "the diet", "wright et", "et al.", "al. 2002", "bergeron et", "al. 2008", "al. 2007", "wright 2013", "2013 .", "sodium/glucose cotransporter 1", "1 slc5a1", "slc5a1 aka sglt1", "sglt1 actively", "actively and reversibly", "and reversibly transports", "reversibly transports glucose", "glucose glc", "glc into", "into cells by", "cells by na+", "by na+ cotransport", "na+ cotransport with", "cotransport with a", "with a na+", "a na+ to", "na+ to glucose", "to glucose coupling", "glucose coupling ratio", "coupling ratio of", "ratio of 2:1.", "of 2:1. slc5a1", "2:1. slc5a1 is", "slc5a1 is mainly", "is mainly expressed", "mainly expressed in", "expressed in the", "in the microvilli", "the microvilli of", "microvilli of intestine", "of intestine and", "intestine and kidney", "and kidney and", "kidney and responsible", "and responsible for", "responsible for the", "for the absorption", "the absorption of", "absorption of sugars.", "of sugars. overexpressed", "sugars. overexpressed slc5a1", "overexpressed slc5a1 has", "slc5a1 has been", "has been found", "been found in", "found in various", "in various cancers", "cancers possibly", "possibly playing a", "playing a role", "a role in", "role in preventing", "in preventing autophagic", "preventing autophagic cell", "autophagic cell death", "cell death by", "death by maintaining", "by maintaining intracellular", "maintaining intracellular glucose", "intracellular glucose levels.", "glucose levels. defects", "levels. defects in", "defects in slc5a1", "in slc5a1 can", "slc5a1 can cause", "can cause congenital", "cause congenital glucose/galactose", "ggm mim:606824", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder manifesting", "disorder manifesting itself", "manifesting itself in", "itself in newborns", "in newborns characterised", "newborns characterised by", "characterised by severe", "severe life", "life threatening diarrhea", "threatening diarrhea which", "diarrhea which is", "which is usually", "is usually fatal", "usually fatal unless", "fatal unless glucose", "unless glucose and", "glucose and galactose", "and galactose are", "galactose are removed", "are removed from", "removed from the", "from the diet", "diet wright", "wright et al.", "et al. 2002", "2002 bergeron", "bergeron et al.", "et al. 2008", "2008 wright", "et al. 2007", "2007 wright", "wright 2013 .", "cotransporter 1 slc5a1", "1 slc5a1 aka", "aka sglt1 actively", "sglt1 actively and", "actively and reversibly transports", "and reversibly transports glucose", "transports glucose glc", "glc into cells", "into cells by na+", "cells by na+ cotransport", "by na+ cotransport with", "na+ cotransport with a", "cotransport with a na+", "with a na+ to", "a na+ to glucose", "na+ to glucose coupling", "to glucose coupling ratio", "glucose coupling ratio of", "coupling ratio of 2:1.", "ratio of 2:1. slc5a1", "of 2:1. slc5a1 is", "2:1. slc5a1 is mainly", "slc5a1 is mainly expressed", "is mainly expressed in", "mainly expressed in the", "expressed in the microvilli", "in the microvilli of", "the microvilli of intestine", "microvilli of intestine and", "of intestine and kidney", "intestine and kidney and", "and kidney and responsible", "kidney and responsible for", "and responsible for the", "responsible for the absorption", "for the absorption of", "the absorption of sugars.", "absorption of sugars. overexpressed", "of sugars. overexpressed slc5a1", "sugars. overexpressed slc5a1 has", "overexpressed slc5a1 has been", "slc5a1 has been found", "has been found in", "been found in various", "found in various cancers", "various cancers possibly", "cancers possibly playing", "possibly playing a role", "playing a role in", "a role in preventing", "role in preventing autophagic", "in preventing autophagic cell", "preventing autophagic cell death", "autophagic cell death by", "cell death by maintaining", "death by maintaining intracellular", "by maintaining intracellular glucose", "maintaining intracellular glucose levels.", "intracellular glucose levels. defects", "glucose levels. defects in", "levels. defects in slc5a1", "defects in slc5a1 can", "in slc5a1 can cause", "slc5a1 can cause congenital", "can cause congenital glucose/galactose", "cause congenital glucose/galactose malabsorption", "mim:606824 an", "606824 an", "an autosomal recessive disorder", "autosomal recessive disorder manifesting", "recessive disorder manifesting itself", "disorder manifesting itself in", "manifesting itself in newborns", "itself in newborns characterised", "in newborns characterised by", "newborns characterised by severe", "by severe life", "severe life threatening", "life threatening diarrhea which", "threatening diarrhea which is", "diarrhea which is usually", "which is usually fatal", "is usually fatal unless", "usually fatal unless glucose", "fatal unless glucose and", "unless glucose and galactose", "glucose and galactose are", "and galactose are removed", "galactose are removed from", "are removed from the", "removed from the diet", "the diet wright", "diet wright et", "wright et al. 2002", "al. 2002 bergeron", "2002 bergeron et", "bergeron et al. 2008", "al. 2008 wright", "2008 wright et", "wright et al. 2007", "al. 2007 wright", "2007 wright 2013", "sodium/glucose cotransporter 1 slc5a1", "cotransporter 1 slc5a1 aka", "1 slc5a1 aka sglt1", "slc5a1 aka sglt1 actively", "aka sglt1 actively and", "sglt1 actively and reversibly", "actively and reversibly transports glucose", "reversibly transports glucose glc", "glucose glc into", "glc into cells by", "into cells by na+ cotransport", "cells by na+ cotransport with", "by na+ cotransport with a", "na+ cotransport with a na+", "cotransport with a na+ to", "with a na+ to glucose", "a na+ to glucose coupling", "na+ to glucose coupling ratio", "to glucose coupling ratio of", "glucose coupling ratio of 2:1.", "coupling ratio of 2:1. slc5a1", "ratio of 2:1. slc5a1 is", "of 2:1. slc5a1 is mainly", "2:1. slc5a1 is mainly expressed", "slc5a1 is mainly expressed in", "is mainly expressed in the", "mainly expressed in the microvilli", "expressed in the microvilli of", "in the microvilli of intestine", "the microvilli of intestine and", "microvilli of intestine and kidney", "of intestine and kidney and", "intestine and kidney and responsible", "and kidney and responsible for", "kidney and responsible for the", "and responsible for the absorption", "responsible for the absorption of", "for the absorption of sugars.", "the absorption of sugars. overexpressed", "absorption of sugars. overexpressed slc5a1", "of sugars. overexpressed slc5a1 has", "sugars. overexpressed slc5a1 has been", "overexpressed slc5a1 has been found", "slc5a1 has been found in", "has been found in various", "been found in various cancers", "in various cancers possibly", "various cancers possibly playing", "cancers possibly playing a", "possibly playing a role in", "playing a role in preventing", "a role in preventing autophagic", "role in preventing autophagic cell", "in preventing autophagic cell death", "preventing autophagic cell death by", "autophagic cell death by maintaining", "cell death by maintaining intracellular", "death by maintaining intracellular glucose", "by maintaining intracellular glucose levels.", "maintaining intracellular glucose levels. defects", "intracellular glucose levels. defects in", "glucose levels. defects in slc5a1", "levels. defects in slc5a1 can", "defects in slc5a1 can cause", "in slc5a1 can cause congenital", "slc5a1 can cause congenital glucose/galactose", "can cause congenital glucose/galactose malabsorption", "malabsorption ggm mim:606824", "mim:606824 an autosomal", "606824 an autosomal", "an autosomal recessive disorder manifesting", "autosomal recessive disorder manifesting itself", "recessive disorder manifesting itself in", "disorder manifesting itself in newborns", "manifesting itself in newborns characterised", "itself in newborns characterised by", "in newborns characterised by severe", "characterised by severe life", "by severe life threatening", "severe life threatening diarrhea", "life threatening diarrhea which is", "threatening diarrhea which is usually", "diarrhea which is usually fatal", "which is usually fatal unless", "is usually fatal unless glucose", "usually fatal unless glucose and", "fatal unless glucose and galactose", "unless glucose and galactose are", "glucose and galactose are removed", "and galactose are removed from", "galactose are removed from the", "are removed from the diet", "from the diet wright", "the diet wright et", "diet wright et al.", "et al. 2002 bergeron", "al. 2002 bergeron et", "2002 bergeron et al.", "et al. 2008 wright", "al. 2008 wright et", "2008 wright et al.", "et al. 2007 wright", "al. 2007 wright 2013", "2007 wright 2013 ." ] }, { "record_id": "GLY_000594_1_1435", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5657560", "r hsa", "hsa 5657560", "r hsa 5657560" ] }, { "record_id": "GLY_000594_1_1435", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hereditary fructose", "fructose 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"methyltransferase activity mitra and", "activity mitra and kaina", "mitra and kaina 1993 ." ] }, { "record_id": "GLY_000594_1_1437", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5659898", "r hsa", "hsa 5659898", "r hsa 5659898" ] }, { "record_id": "GLY_000594_1_1437", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "intestinal saccharidase", "saccharidase deficiencies", "intestinal saccharidase deficiencies", "defects in", "in in", "in two", "two enzymes", "enzymes required", "required for", "for intestinal", "intestinal digestion", "digestion of", "of dietary", "dietary carbohydrate", "a domain", "domain of", "of lactase", "lactase phlorizin", "phlorizin hydrolase", "hydrolase protein", "and sucrase", "sucrase isomaltase", "are annotated", "annotated here.", "here. the", "the first", "first affects", "affects nursing", "nursing infants", "the second", "second affects", "affects 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              the", ".

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              the", "2009 .

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              the", "al. 2009 .

              the starch", "2009 .

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              the disaccharide lactose", "after weaning.

              the disaccharide lactose is", "weaning.

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              the", "et al. 2009 .

              the starch", "al. 2009 .

              the starch in", "2009 .

              the starch in a", ".

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              ", "slc7a7 encodes the y+l amino", "encodes the y+l amino acid", "the y+l amino acid transporter", "y+l amino acid transporter 1", "acid transporter 1 y+lat1", "transporter 1 y+lat1 .", "1 y+lat1 . as", "y+lat1 . as a heterodimer", ". as a heterodimer with", "as a heterodimer with slc3a2", "a heterodimer with slc3a2 in", "heterodimer with slc3a2 in the", "with slc3a2 in the plasma", "slc3a2 in the plasma membrane", "the plasma membrane slc7a7", "plasma membrane slc7a7 mediates", "membrane slc7a7 mediates the", "slc7a7 mediates the exchange of", "mediates the exchange of arginine", "exchange of arginine l", "of arginine l arg", "l arg for leucine", "for leucine l leu", "l leu and a", "leu and a sodium", "a sodium ion na+", "sodium ion na+ .", "ion na+ . the", "na+ . the physiological concentrations", ". the physiological concentrations of", "the physiological concentrations of arginine", "physiological concentrations of arginine and", "concentrations of arginine and leucine", "of arginine and leucine are", "arginine and leucine are expected", "and leucine are expected to", "leucine are expected to favor", "are expected to favor arginine", "expected to favor arginine export", "favor arginine export schweikhard", "arginine export schweikhard &", "export schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . defects", "ziegler 2012 . defects in", "2012 . defects in slc7a7", ". defects in slc7a7 can", "defects in slc7a7 can cause", "in slc7a7 can cause lysinuric", "slc7a7 can cause lysinuric protein", "can cause lysinuric protein intolerance", "intolerance lpi mim:222700", "mim:222700 a metabolic", "222700 a metabolic", "a metabolic disorder characterised by", "metabolic disorder characterised by decreased", "disorder characterised by decreased cationic", "characterised by decreased cationic amino", "by decreased cationic amino acid", "cationic amino acid caa", "acid caa transport", "caa transport at the", "transport at the basolateral membrane", "at the basolateral membrane of", "the basolateral membrane of epithelial", "basolateral membrane of epithelial cells", "membrane of epithelial cells in", "of epithelial cells in the", "epithelial cells in the intestine", "cells in the intestine and", "in the intestine and kidney", "intestine and kidney increased", "and kidney increased renal", "kidney increased renal excretion", "increased renal excretion of caa", "renal excretion of caa and", "excretion of caa and orotic", "of caa and orotic aciduria.", "caa and orotic aciduria. there", "and orotic aciduria. there is", "orotic aciduria. there is extreme", "aciduria. there is extreme variability", "there is extreme variability clinically", "is extreme variability clinically but", "extreme variability clinically but typical", "variability clinically but typical symptoms", "clinically but typical symptoms include", "but typical symptoms include refusal", "typical symptoms include refusal to", "symptoms include refusal to feed", "refusal to feed vomiting", "to feed vomiting and", "feed vomiting and consequent", "vomiting and consequent failure to", "and consequent failure to thrive.", "consequent failure to thrive. hepatosplenomegaly", "to thrive. hepatosplenomegaly hematological", "thrive. hepatosplenomegaly hematological anomalies", "hepatosplenomegaly hematological anomalies and", "hematological anomalies and neurological involvement", "anomalies and neurological involvement are", "and neurological involvement are recurrent", "neurological involvement are recurrent clinical", "involvement are recurrent clinical features", "recurrent clinical features sperandeo", "clinical features sperandeo et", "features sperandeo et al.", "et al. 2008 sebastio", "al. 2008 sebastio et", "2008 sebastio et al.", "sebastio et al. 2011 .
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"heavy metals reviewed in", "metals reviewed in sharma", "reviewed in sharma et al.", "in sharma et al. 2013", "al. 2013 storing", "2013 storing and", "and transporting zinc and", "transporting zinc and redox", "zinc and redox biochemistry.", "and redox biochemistry. metallothioneins interact", "redox biochemistry. metallothioneins interact with", "biochemistry. metallothioneins interact with many", "metallothioneins interact with many other", "interact with many other cellular", "with many other cellular proteins", "other cellular proteins with", "cellular proteins with most", "proteins with most interactions", "with most interactions involving proteins", "most interactions involving proteins of", "interactions involving proteins of the", "involving proteins of the central", "proteins of the central nervous", "of the central nervous system", "central nervous system reviewed", "nervous system reviewed in", "system reviewed in atrian", "reviewed in atrian and capdevila", "in atrian and capdevila 2013", "atrian and capdevila 2013 ." ] }, { "record_id": "GLY_000594_1_1441", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5662702", "r hsa", "hsa 5662702", "r hsa 5662702" ] }, { "record_id": "GLY_000594_1_1441", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "melanin biosynthesis", "biosynthesis takes", "takes place", "place in", "in specialized", "specialized cells", "cells called", "called melanocytes", "within membrane", "membrane bound", "bound organelles", "organelles referred", "referred to", "to as", "as melanosomes.", "melanosomes. melanosomes", "melanosomes are", "are transferred", "transferred via", "via dendrites", "dendrites to", "to surrounding", "surrounding keratinocytes.", "keratinocytes. keratinocytes", "keratinocytes and", "and melanocytes", "melanocytes are", "are collectively", "collectively known", "known as", "as 'the", "'the epidermal", "epidermal melanin", "melanin unit'.", "unit'. each", "each melanocyte", "melanocyte is", "is in", "in contact", "contact with", "with approximately", "approximately 40", "40 keratinocytes", "keratinocytes in", "in the", "the basal", "basal and", "and suprabasal", "suprabasal layers", "cichorek et", "et al.", "al. 2013", "2013 .", ". melanocytes", "are distributed", "distributed in", "the epidermis", "hair follicles", "the inner", "inner ear", "ear and", "and the", "the eye", "yamaguchi et", "al. 2007", "tolleson 2005", "2005 .", ".

              melanocytes", "

              melanocytes in", "in mammals", "mammals and", "and birds", "birds produce", "produce two", "two chemically", "chemically distinct", "distinct types", "types of", "of melanin", "black to", "to brown", "brown eumelanin", "eumelanin and", "and yellow", "yellow to", "to reddish", "reddish brown", "brown pheomelanin", "ito &", "& wakamatsu", "wakamatsu 2008", "simon et", "al. 2009", "d'ischia et", ". these", "these differ", "differ in", "in their", "their responses", "responses to", "to uv", "uv radiation", "eumelanin has", "has the", "the ability", "ability to", "to convert", "convert absorbed", "absorbed light", "light energy", "energy into", "into heat", "heat energy", "meredith &", "& riesz", "riesz 2004", "and to", "to detoxify", "detoxify reactive", "reactive oxygen", "oxygen species", "bustamante et", "al. 1993", "while pheomelanin", "pheomelanin is", "is a", "a phototoxic", "phototoxic pro", "pro oxidant", "samokhvalov 2005", ". most", "most natural", "natural melanin", "melanin pigments", "pigments contain", "contain eumelanin", "and pheomelanin", "wakamatsu 2003", "and are", "are termed", "termed 'mixed'", "'mixed' melanins.", "melanins. neuromelanins", "neuromelanins are", "are mixed", "mixed melanin", "melanin like", "like pigments", "pigments which", "which are", "are mainly", "mainly found", "found in", "in neurons", "neurons of", "of the", "the substantia", "substantia nigra", "nigra and", "and locus", "locus coeruleus", "fedorow et", "al. 2005", ". synthesis", "synthesis of", "of nm", "nm may", "may prevent", "prevent the", "the accumulation", "accumulation of", "of toxic", "toxic catechol", "catechol derivatives", "zecca et", "al. 2003", "2003 .", ". nm", "nm can", "can sequester", "sequester a", "a variety", "variety of", "of potentially", "potentially damaging", "damaging molecules", "molecules such", "such as", "as beta", "beta carbolines", "heavy metal", "metal ions", "ions and", "and 1", "1 methyl", "methyl 4", "4 phenylpyridinium", "d'amato et", "al. 1986", "a drug", "drug which", "which causes", "causes parkinson's", "parkinson's disease", "disease like", "like symptoms.", "models suggest", "suggest that", "that mixed", "mixed melanogenesis", "melanogenesis occurs", "occurs in", "in three", "three stages", "ito et", "al. 2000", "2000 .", ". the", "the initial", "initial stage", "stage of", "biosynthesis is", "is the", "the production", "production of", "of cysteinyldopas", "which continues", "continues while", "while sufficient", "sufficient cysteine", "cysteine is", "is available.", "available. the", "the second", "second stage", "stage is", "the oxidation", "oxidation of", "cysteinyldopas to", "to produce", "produce pheomelanin", "while cysteinyldopa", "cysteinyldopa concentration", "concentration is", "is sufficiently", "sufficiently high.", "high. the", "the last", "last stage", "of eumelanin", "which begins", "begins when", "when cysteinyldopas", "cysteinyldopas and", "and cysteine", "cysteine are", "are depleted.", "depleted. the", "the ratio", "ratio of", "eumelanin to", "to pheomelanin", "is determined", "determined by", "by tyrosinase", "tyrosinase activity", "activity and", "the availability", "availability of", "of tyrosine", "tyrosine and", "land et", "melanin biosynthesis takes", "biosynthesis takes place", "takes place in", "place in specialized", "in specialized cells", "specialized cells called", "cells called melanocytes", "melanocytes within", "within membrane bound", "membrane bound organelles", "bound organelles referred", "organelles referred to", "referred to as", "to as melanosomes.", "as melanosomes. melanosomes", "melanosomes. melanosomes are", "melanosomes are transferred", "are transferred via", "transferred via dendrites", "via dendrites to", "dendrites to surrounding", "to surrounding keratinocytes.", "surrounding keratinocytes. keratinocytes", "keratinocytes. keratinocytes and", "keratinocytes and melanocytes", "and melanocytes are", "melanocytes are collectively", "are collectively known", "collectively known as", "known as 'the", "as 'the epidermal", "'the epidermal melanin", "epidermal melanin unit'.", "melanin unit'. each", "unit'. each melanocyte", "each melanocyte is", "melanocyte is in", "is in contact", "in contact with", "contact with approximately", "with approximately 40", "approximately 40 keratinocytes", "40 keratinocytes in", "keratinocytes in the", "in the basal", "the basal and", "basal and suprabasal", "and suprabasal layers", "layers cichorek", "cichorek et al.", "et al. 2013", "al. 2013 .", "2013 . melanocytes", ". melanocytes are", "melanocytes are distributed", "are distributed in", "distributed in the", "in the epidermis", "epidermis hair", "follicles the", "the inner ear", "inner ear and", "ear and the", "and the eye", "eye yamaguchi", "yamaguchi et al.", "et al. 2007", "2007 tolleson", "tolleson 2005 .", "2005 .

              melanocytes", ".

              melanocytes in", "

              melanocytes in mammals", "in mammals and", "mammals and birds", "and birds produce", "birds produce two", "produce two chemically", "two chemically distinct", "chemically distinct types", "distinct types of", "types of melanin", "melanin black", "black to brown", "to brown eumelanin", "brown eumelanin and", "eumelanin and yellow", "and yellow to", "yellow to reddish", "to reddish brown", "reddish brown pheomelanin", "pheomelanin ito", "ito & wakamatsu", "& wakamatsu 2008", "2008 simon", "simon et al.", "et al. 2009", "2009 d'ischia", "d'ischia et al.", "2013 . these", ". these differ", "these differ in", "differ in their", "in their responses", "their responses to", "responses to uv", "to uv radiation", "radiation eumelanin", "eumelanin has the", "has the ability", "the ability to", "ability to convert", "to convert absorbed", "convert absorbed light", "absorbed light energy", "light energy into", "energy into heat", "into heat energy", "energy meredith", "meredith & riesz", "& riesz 2004", "2004 and", "and to detoxify", "to detoxify reactive", "detoxify reactive oxygen", "reactive oxygen species", "species ros", "bustamante et al.", "et al. 1993", "while pheomelanin is", "pheomelanin is a", "is a phototoxic", "a phototoxic pro", "phototoxic pro oxidant", "oxidant samokhvalov", "samokhvalov 2005 .", "2005 . most", ". most natural", "most natural melanin", "natural melanin pigments", "melanin pigments contain", "pigments contain eumelanin", "contain eumelanin and", "eumelanin and pheomelanin", "& wakamatsu 2003", "2003 and", "and are termed", "are termed 'mixed'", "termed 'mixed' melanins.", "'mixed' melanins. neuromelanins", "melanins. neuromelanins are", "neuromelanins are mixed", "are mixed melanin", "mixed melanin like", "melanin like pigments", "like pigments which", "pigments which are", "which are mainly", "are mainly found", "mainly found in", "found in neurons", "in neurons of", "neurons of the", "of the substantia", "the substantia nigra", "substantia nigra and", "nigra and locus", "and locus coeruleus", "coeruleus fedorow", "fedorow et al.", "et al. 2005", "al. 2005 .", "2005 . synthesis", ". synthesis of", "synthesis of nm", "of nm may", "nm may prevent", "may prevent the", "prevent the accumulation", "the accumulation of", "accumulation of toxic", "of toxic catechol", "toxic catechol derivatives", "derivatives zecca", "zecca et al.", "et al. 2003", "al. 2003 .", "2003 . nm", ". nm can", "nm can sequester", "can sequester a", "sequester a variety", "a variety of", "variety of potentially", "of potentially damaging", "potentially damaging molecules", "damaging molecules such", "molecules such as", "such as beta", "as beta carbolines", "carbolines heavy", "heavy metal ions", "metal ions and", "ions and 1", "and 1 methyl", "1 methyl 4", "methyl 4 phenylpyridinium", "phenylpyridinium mpp+", "d'amato et al.", "et al. 1986", "a drug which", "drug which causes", "which causes parkinson's", "causes parkinson's disease", "parkinson's disease like", "disease like symptoms.", "symptoms. models", "models suggest that", "suggest that mixed", "that mixed melanogenesis", "mixed melanogenesis occurs", "melanogenesis occurs in", "occurs in three", "in three stages", "stages ito", "ito et al.", "et al. 2000", "al. 2000 .", "2000 . the", ". the initial", "the initial stage", "initial stage of", "stage of melanin", "of melanin biosynthesis", "melanin biosynthesis is", "biosynthesis is the", "is the production", "the production of", "production of cysteinyldopas", "cysteinyldopas which", "which continues while", "continues while sufficient", "while sufficient cysteine", "sufficient cysteine is", "cysteine is available.", "is available. the", "available. the second", "the second stage", "second stage is", "stage is the", "is the oxidation", "the oxidation of", "oxidation of cysteinyldopas", "of cysteinyldopas to", "cysteinyldopas to produce", "to produce pheomelanin", "pheomelanin which", "continues while cysteinyldopa", "while cysteinyldopa concentration", "cysteinyldopa concentration is", "concentration is sufficiently", "is sufficiently high.", "sufficiently high. the", "high. the last", "the last stage", "last stage is", "production of eumelanin", "eumelanin which", "which begins when", "begins when cysteinyldopas", "when cysteinyldopas and", "cysteinyldopas and cysteine", "and cysteine are", "cysteine are depleted.", "are depleted. the", "depleted. the ratio", "the ratio of", "ratio of eumelanin", "of eumelanin to", "eumelanin to pheomelanin", "to pheomelanin is", "pheomelanin is determined", "is determined by", "determined by tyrosinase", "by tyrosinase activity", "tyrosinase activity and", "activity and the", "and the availability", "the availability of", "availability of tyrosine", "of tyrosine and", "tyrosine and cysteine", "cysteine land", "land et al.", "melanin biosynthesis takes place", "biosynthesis takes place in", "takes place in specialized", "place in specialized cells", "in specialized cells called", "specialized cells called melanocytes", "called melanocytes within", "melanocytes within membrane", "within membrane bound organelles", "membrane bound organelles referred", "bound organelles referred to", "organelles referred to as", "referred to as melanosomes.", "to as melanosomes. melanosomes", "as melanosomes. melanosomes are", "melanosomes. melanosomes are transferred", "melanosomes are transferred via", "are transferred via dendrites", "transferred via dendrites to", "via dendrites to surrounding", "dendrites to surrounding keratinocytes.", "to surrounding keratinocytes. keratinocytes", "surrounding keratinocytes. keratinocytes and", "keratinocytes. keratinocytes and melanocytes", "keratinocytes and melanocytes are", "and melanocytes are collectively", "melanocytes are collectively known", "are collectively known as", "collectively known as 'the", "known as 'the epidermal", "as 'the epidermal melanin", "'the epidermal melanin unit'.", "epidermal melanin unit'. each", "melanin unit'. each melanocyte", "unit'. each melanocyte is", "each melanocyte is in", "melanocyte is in contact", "is in contact with", "in contact with approximately", "contact with approximately 40", "with approximately 40 keratinocytes", "approximately 40 keratinocytes in", "40 keratinocytes in the", "keratinocytes in the basal", "in the basal and", "the basal and suprabasal", "basal and suprabasal layers", "suprabasal layers cichorek", "layers cichorek et", "cichorek et al. 2013", "et al. 2013 .", "al. 2013 . melanocytes", "2013 . melanocytes are", ". melanocytes are distributed", "melanocytes are distributed in", "are distributed in the", "distributed in the epidermis", "the epidermis hair", "epidermis hair follicles", "hair follicles the", "follicles the inner", "the inner ear and", "inner ear and the", "ear and the eye", "the eye yamaguchi", "eye yamaguchi et", "yamaguchi et al. 2007", "al. 2007 tolleson", "2007 tolleson 2005", "tolleson 2005 .

              melanocytes", "2005 .

              melanocytes in", ".

              melanocytes in mammals", "

              melanocytes in mammals and", "in mammals and birds", "mammals and birds produce", "and birds produce two", "birds produce two chemically", "produce two chemically distinct", "two chemically distinct types", "chemically distinct types of", "distinct types of melanin", "of melanin black", "melanin black to", "black to brown eumelanin", "to brown eumelanin and", "brown eumelanin and yellow", "eumelanin and yellow to", "and yellow to reddish", "yellow to reddish brown", "to reddish brown pheomelanin", "brown pheomelanin ito", "pheomelanin ito &", "ito & wakamatsu 2008", "wakamatsu 2008 simon", "2008 simon et", "simon et al. 2009", "al. 2009 d'ischia", "2009 d'ischia et", "d'ischia et al. 2013", "al. 2013 . these", "2013 . these differ", ". these differ in", "these differ in their", "differ in their responses", "in their responses to", "their responses to uv", "responses to uv radiation", "uv radiation eumelanin", "radiation eumelanin has", "eumelanin has the ability", "has the ability to", "the ability to convert", "ability to convert absorbed", "to convert absorbed light", "convert absorbed light energy", "absorbed light energy into", "light energy into heat", "energy into heat energy", "heat energy meredith", "energy meredith &", "meredith & riesz 2004", "riesz 2004 and", "2004 and to", "and to detoxify reactive", "to detoxify reactive oxygen", "detoxify reactive oxygen species", "oxygen species ros", "ros bustamante", "bustamante et al. 1993", "1993 while", "while pheomelanin is a", "pheomelanin is a phototoxic", "is a phototoxic pro", "a phototoxic pro oxidant", "pro oxidant samokhvalov", "oxidant samokhvalov 2005", "samokhvalov 2005 . most", "2005 . most natural", ". most natural melanin", "most natural melanin pigments", "natural melanin pigments contain", "melanin pigments contain eumelanin", "pigments contain eumelanin and", "contain eumelanin and pheomelanin", "and pheomelanin ito", "ito & wakamatsu 2003", "wakamatsu 2003 and", "2003 and are", "and are termed 'mixed'", "are termed 'mixed' melanins.", "termed 'mixed' melanins. neuromelanins", "'mixed' melanins. neuromelanins are", "melanins. neuromelanins are mixed", "neuromelanins are mixed melanin", "are mixed melanin like", "mixed melanin like pigments", "melanin like pigments which", "like pigments which are", "pigments which are mainly", "which are mainly found", "are mainly found in", "mainly found in neurons", "found in neurons of", "in neurons of the", "neurons of the substantia", "of the substantia nigra", "the substantia nigra and", "substantia nigra and locus", "nigra and locus coeruleus", "locus coeruleus fedorow", "coeruleus fedorow et", "fedorow et al. 2005", "et al. 2005 .", "al. 2005 . synthesis", "2005 . synthesis of", ". synthesis of nm", "synthesis of nm may", "of nm may prevent", "nm may prevent the", "may prevent the accumulation", "prevent the accumulation of", "the accumulation of toxic", "accumulation of toxic catechol", "of toxic catechol derivatives", "catechol derivatives zecca", "derivatives zecca et", "zecca et al. 2003", "et al. 2003 .", "al. 2003 . nm", "2003 . nm can", ". nm can sequester", "nm can sequester a", "can sequester a variety", "sequester a variety of", "a variety of potentially", "variety of potentially damaging", "of potentially damaging molecules", "potentially damaging molecules such", "damaging molecules such as", "molecules such as beta", "such as beta carbolines", "beta carbolines heavy", "carbolines heavy metal", "heavy metal ions and", "metal ions and 1", "ions and 1 methyl", "and 1 methyl 4", "1 methyl 4 phenylpyridinium", "4 phenylpyridinium mpp+", "mpp+ d'amato", "d'amato et al. 1986", "1986 a", "a drug which causes", "drug which causes parkinson's", "which causes parkinson's disease", "causes parkinson's disease like", "parkinson's disease like symptoms.", "like symptoms. models", "symptoms. models suggest", "models suggest that mixed", "suggest that mixed melanogenesis", "that mixed melanogenesis occurs", "mixed melanogenesis occurs in", "melanogenesis occurs in three", "occurs in three stages", "three stages ito", "stages ito et", "ito et al. 2000", "et al. 2000 .", "al. 2000 . the", "2000 . the initial", ". the initial stage", "the initial stage of", "initial stage of melanin", "stage of melanin biosynthesis", "of melanin biosynthesis is", "melanin biosynthesis is the", "biosynthesis is the production", "is the production of", "the production of cysteinyldopas", "of cysteinyldopas which", "cysteinyldopas which continues", "which continues while sufficient", "continues while sufficient cysteine", "while sufficient cysteine is", "sufficient cysteine is available.", "cysteine is available. the", "is available. the second", "available. the second stage", "the second stage is", "second stage is the", "stage is the oxidation", "is the oxidation of", "the oxidation of cysteinyldopas", "oxidation of cysteinyldopas to", "of cysteinyldopas to produce", "cysteinyldopas to produce pheomelanin", "produce pheomelanin which", "pheomelanin which continues", "which continues while cysteinyldopa", "continues while cysteinyldopa concentration", "while cysteinyldopa concentration is", "cysteinyldopa concentration is sufficiently", "concentration is sufficiently high.", "is sufficiently high. the", "sufficiently high. the last", "high. the last stage", "the last stage is", "last stage is the", "stage is the production", "the production of eumelanin", "of eumelanin which", "eumelanin which begins", "which begins when cysteinyldopas", "begins when cysteinyldopas and", "when cysteinyldopas and cysteine", "cysteinyldopas and cysteine are", "and cysteine are depleted.", "cysteine are depleted. the", "are depleted. the ratio", "depleted. the ratio of", "the ratio of eumelanin", "ratio of eumelanin to", "of eumelanin to pheomelanin", "eumelanin to pheomelanin is", "to pheomelanin is determined", "pheomelanin is determined by", "is determined by tyrosinase", "determined by tyrosinase activity", "by tyrosinase activity and", "tyrosinase activity and the", "activity and the availability", "and the availability of", "the availability of tyrosine", "availability of tyrosine and", "of tyrosine and cysteine", "and cysteine land", "cysteine land et", "land et al. 2003", "melanin biosynthesis takes place in", "biosynthesis takes place in specialized", "takes place in specialized cells", "place in specialized cells called", "in specialized cells called melanocytes", "cells called melanocytes within", "called melanocytes within membrane", "melanocytes within membrane bound", "within membrane bound organelles referred", "membrane bound organelles referred to", "bound organelles referred to as", "organelles referred to as melanosomes.", "referred to as melanosomes. melanosomes", "to as melanosomes. melanosomes are", "as melanosomes. melanosomes are transferred", "melanosomes. melanosomes are transferred via", "melanosomes are transferred via dendrites", "are transferred via dendrites to", "transferred via dendrites to surrounding", "via dendrites to surrounding keratinocytes.", "dendrites to surrounding keratinocytes. keratinocytes", "to surrounding keratinocytes. keratinocytes and", "surrounding keratinocytes. keratinocytes and melanocytes", "keratinocytes. keratinocytes and melanocytes are", "keratinocytes and melanocytes are collectively", "and melanocytes are collectively known", "melanocytes are collectively known as", "are collectively known as 'the", "collectively known as 'the epidermal", "known as 'the epidermal melanin", "as 'the epidermal melanin unit'.", "'the epidermal melanin unit'. each", "epidermal melanin unit'. each melanocyte", "melanin unit'. each melanocyte is", "unit'. each melanocyte is in", "each melanocyte is in contact", "melanocyte is in contact with", "is in contact with approximately", "in contact with approximately 40", "contact with approximately 40 keratinocytes", "with approximately 40 keratinocytes in", "approximately 40 keratinocytes in the", "40 keratinocytes in the basal", "keratinocytes in the basal and", "in the basal and suprabasal", "the basal and suprabasal layers", "and suprabasal layers cichorek", "suprabasal layers cichorek et", "layers cichorek et al.", "cichorek et al. 2013 .", "et al. 2013 . melanocytes", "al. 2013 . melanocytes are", "2013 . melanocytes are distributed", ". melanocytes are distributed in", "melanocytes are distributed in the", "are distributed in the epidermis", "in the epidermis hair", "the epidermis hair follicles", "hair follicles the inner", "follicles the inner ear", "the inner ear and the", "inner ear and the eye", "and the eye yamaguchi", "the eye yamaguchi et", "eye yamaguchi et al.", "et al. 2007 tolleson", "al. 2007 tolleson 2005", "2007 tolleson 2005 .", "tolleson 2005 .

              melanocytes in", "2005 .

              melanocytes in mammals", ".

              melanocytes in mammals and", "

              melanocytes in mammals and birds", "in mammals and birds produce", "mammals and birds produce two", "and birds produce two chemically", "birds produce two chemically distinct", "produce two chemically distinct types", "two chemically distinct types of", "chemically distinct types of melanin", "types of melanin black", "of melanin black to", "melanin black to brown", "black to brown eumelanin and", "to brown eumelanin and yellow", "brown eumelanin and yellow to", "eumelanin and yellow to reddish", "and yellow to reddish brown", "yellow to reddish brown pheomelanin", "reddish brown pheomelanin ito", "brown pheomelanin ito &", "pheomelanin ito & wakamatsu", "& wakamatsu 2008 simon", "wakamatsu 2008 simon et", "2008 simon et al.", "et al. 2009 d'ischia", "al. 2009 d'ischia et", "2009 d'ischia et al.", "d'ischia et al. 2013 .", "et al. 2013 . these", "al. 2013 . these differ", "2013 . these differ in", ". these differ in their", "these differ in their responses", "differ in their responses to", "in their responses to uv", "their responses to uv radiation", "to uv radiation eumelanin", "uv radiation eumelanin has", "radiation eumelanin has the", "eumelanin has the ability to", "has the ability to convert", "the ability to convert absorbed", "ability to convert absorbed light", "to convert absorbed light energy", "convert absorbed light energy into", "absorbed light energy into heat", "light energy into heat energy", "into heat energy meredith", "heat energy meredith &", "energy meredith & riesz", "& riesz 2004 and", "riesz 2004 and to", "2004 and to detoxify", "and to detoxify reactive oxygen", "to detoxify reactive oxygen species", "reactive oxygen species ros", "ros bustamante et", "al. 1993 while", "1993 while pheomelanin", "while pheomelanin is a phototoxic", "pheomelanin is a phototoxic pro", "is a phototoxic pro oxidant", "phototoxic pro oxidant samokhvalov", "pro oxidant samokhvalov 2005", "oxidant samokhvalov 2005 .", "samokhvalov 2005 . most natural", "2005 . most natural melanin", ". most natural melanin pigments", "most natural melanin pigments contain", "natural melanin pigments contain eumelanin", "melanin pigments contain eumelanin and", "pigments contain eumelanin and pheomelanin", "eumelanin and pheomelanin ito", "and pheomelanin ito &", "& wakamatsu 2003 and", "wakamatsu 2003 and are", "2003 and are termed", "and are termed 'mixed' melanins.", "are termed 'mixed' melanins. neuromelanins", "termed 'mixed' melanins. neuromelanins are", "'mixed' melanins. neuromelanins are mixed", "melanins. neuromelanins are mixed melanin", "neuromelanins are mixed melanin like", "are mixed melanin like pigments", "mixed melanin like pigments which", "melanin like pigments which are", "like pigments which are mainly", "pigments which are mainly found", "which are mainly found in", "are mainly found in neurons", "mainly found in neurons of", "found in neurons of the", "in neurons of the substantia", "neurons of the substantia nigra", "of the substantia nigra and", "the substantia nigra and locus", "substantia nigra and locus coeruleus", "and locus coeruleus fedorow", "locus coeruleus fedorow et", "coeruleus fedorow et al.", "fedorow et al. 2005 .", "et al. 2005 . synthesis", "al. 2005 . synthesis of", "2005 . synthesis of nm", ". synthesis of nm may", "synthesis of nm may prevent", "of nm may prevent the", "nm may prevent the accumulation", "may prevent the accumulation of", "prevent the accumulation of toxic", "the accumulation of toxic catechol", "accumulation of toxic catechol derivatives", "toxic catechol derivatives zecca", "catechol derivatives zecca et", "derivatives zecca et al.", "zecca et al. 2003 .", "et al. 2003 . nm", "al. 2003 . nm can", "2003 . nm can sequester", ". nm can sequester a", "nm can sequester a variety", "can sequester a variety of", "sequester a variety of potentially", "a variety of potentially damaging", "variety of potentially damaging molecules", "of potentially damaging molecules such", "potentially damaging molecules such as", "damaging molecules such as beta", "molecules such as beta carbolines", "as beta carbolines heavy", "beta carbolines heavy metal", "carbolines heavy metal ions", "heavy metal ions and 1", "metal ions and 1 methyl", "ions and 1 methyl 4", "and 1 methyl 4 phenylpyridinium", "methyl 4 phenylpyridinium mpp+", "mpp+ d'amato et", "al. 1986 a", "1986 a drug", "a drug which causes parkinson's", "drug which causes parkinson's disease", "which causes parkinson's disease like", "causes parkinson's disease like symptoms.", "disease like symptoms. models", "like symptoms. models suggest", "symptoms. models suggest that", "models suggest that mixed melanogenesis", "suggest that mixed melanogenesis occurs", "that mixed melanogenesis occurs in", "mixed melanogenesis occurs in three", "melanogenesis occurs in three stages", "in three stages ito", "three stages ito et", "stages ito et al.", "ito et al. 2000 .", "et al. 2000 . the", "al. 2000 . the initial", "2000 . the initial stage", ". the initial stage of", "the initial stage of melanin", "initial stage of melanin biosynthesis", "stage of melanin biosynthesis is", "of melanin biosynthesis is the", "melanin biosynthesis is the production", "biosynthesis is the production of", "is the production of cysteinyldopas", "production of cysteinyldopas which", "of cysteinyldopas which continues", "cysteinyldopas which continues while", "which continues while sufficient cysteine", "continues while sufficient cysteine is", "while sufficient cysteine is available.", "sufficient cysteine is available. the", "cysteine is available. the second", "is available. the second stage", "available. the second stage is", "the second stage is the", "second stage is the oxidation", "stage is the oxidation of", "is the oxidation of cysteinyldopas", "the oxidation of cysteinyldopas to", "oxidation of cysteinyldopas to produce", "of cysteinyldopas to produce pheomelanin", "to produce pheomelanin which", "produce pheomelanin which continues", "pheomelanin which continues while", "which continues while cysteinyldopa concentration", "continues while cysteinyldopa concentration is", "while cysteinyldopa concentration is sufficiently", "cysteinyldopa concentration is sufficiently high.", "concentration is sufficiently high. the", "is sufficiently high. the last", "sufficiently high. the last stage", "high. the last stage is", "the last stage is the", "last stage is the production", "stage is the production of", "is the production of eumelanin", "production of eumelanin which", "of eumelanin which begins", "eumelanin which begins when", "which begins when cysteinyldopas and", "begins when cysteinyldopas and cysteine", "when cysteinyldopas and cysteine are", "cysteinyldopas and cysteine are depleted.", "and cysteine are depleted. the", "cysteine are depleted. the ratio", "are depleted. the ratio of", "depleted. the ratio of eumelanin", "the ratio of eumelanin to", "ratio of eumelanin to pheomelanin", "of eumelanin to pheomelanin is", "eumelanin to pheomelanin is determined", "to pheomelanin is determined by", "pheomelanin is determined by tyrosinase", "is determined by tyrosinase activity", "determined by tyrosinase activity and", "by tyrosinase activity and the", "tyrosinase activity and the availability", "activity and the availability of", "and the availability of tyrosine", "the availability of tyrosine and", "availability of tyrosine and cysteine", "tyrosine and cysteine land", "and cysteine land et", "cysteine land et al.", "land et al. 2003 ." ] }, { "record_id": "GLY_000594_1_1442", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5668599", "r hsa", "hsa 5668599", "r hsa 5668599" ] }, { "record_id": "GLY_000594_1_1442", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rho gtpases", "gtpases activate", "activate nadph", "nadph oxidases", "rho gtpases activate", "gtpases activate nadph", "activate nadph oxidases", "rho gtpases activate nadph", "gtpases activate nadph oxidases", "rho gtpases activate nadph oxidases", "are membrane", "membrane associated", "associated enzymatic", "enzymatic complexes", "complexes that", "that use", "use nadph", "nadph as", "as an", "an electon", "electon donor", "donor to", "to reduce", "reduce oxygen", "oxygen and", "and produce", "produce superoxide", "that serves", "serves as", "as a", "a secondary", "secondary messenger", "brown and", "and griendling", "griendling 2009", "2009 .

              nox2", ".

              nox2 complex", "complex consists", "consists of", "of cybb", "and ncf4", "p40ohox .", ". rac1:gtp", "rac1:gtp binds", "binds nox2", "nox2 complex", "complex in", "in response", "response to", "to vegf", "vegf signaling", "signaling by", "by directly", "directly interracting", "interracting with", "with cybb", "cybb and", "and ncf2", "leading to", "to enhancement", "enhancement of", "of vegf", "signaling through", "through vegf", "vegf receptor", "receptor vegfr2", "which plays", "plays a", "a role", "role in", "in angiogenesis", "price et", "et al.", "al. 2002", "bedard and", "and krause", "krause 2007", "2007 .", ". rac2:gtp", "rac2:gtp can", "can also", "also activate", "activate the", "the nox2", "complex by", "by binding", "binding to", "to cybb", "to production", "production of", "of superoxide", "superoxide in", "in phagosomes", "phagosomes of", "of neutrophils", "neutrophils which", "which is", "is necessary", "necessary fo", "fo the", "the microbicidal", "microbicidal activity", "activity of", "knaus et", "al. 1991", "roberts et", "al. 1999", "kim and", "and dinauer", "dinauer 2001", "jyoti et", "al. 2014", "2014 .

              nox1", ".

              nox1 complex", "composed of", "of nox1", "noxo1 and", "and cyba", "and nox3", "nox3 complex", "of nox3", "ncf1 amd", "amd ncf2", "ncf2 or", "or noxa1", "also be", "be activated", "activated by", "to rac1:gtp", "rac1:gtp to", "to produce", "cheng et", "al. 2006", "miyano et", "ueyama et", "2006 .", "oxidases nox", "nox are", "are membrane associated", "membrane associated enzymatic", "associated enzymatic complexes", "enzymatic complexes that", "complexes that use", "that use nadph", "use nadph as", "nadph as an", "as an electon", "an electon donor", "electon donor to", "donor to reduce", "to reduce oxygen", "reduce oxygen and", "oxygen and produce", "and produce superoxide", "superoxide o2", "that serves as", "serves as a", "as a secondary", "a secondary messenger", "messenger brown", "brown and griendling", "and griendling 2009", "griendling 2009 .

              nox2", "2009 .

              nox2 complex", ".

              nox2 complex consists", "complex consists of", "consists of cybb", "cybb nox2", "cyba p22phox", "ncf1 p47phox", "ncf2 p67phox", "p67phox and", "ncf4 p40ohox", "p40ohox . rac1:gtp", ". rac1:gtp binds", "rac1:gtp binds nox2", "binds nox2 complex", "nox2 complex in", "complex in response", "in response to", "response to vegf", "to vegf signaling", "vegf signaling by", "signaling by directly", "by directly interracting", "directly interracting with", "interracting with cybb", "with cybb and", "cybb and ncf2", "ncf2 leading", "leading to enhancement", "to enhancement of", "enhancement of vegf", "of vegf signaling", "vegf signaling through", "signaling through vegf", "through vegf receptor", "vegf receptor vegfr2", "vegfr2 which", "which plays a", "plays a role", "a role in", "role in angiogenesis", "angiogenesis price", "price et al.", "et al. 2002", "2002 bedard", "bedard and krause", "and krause 2007", "krause 2007 .", "2007 . rac2:gtp", ". rac2:gtp can", "rac2:gtp can also", "can also activate", "also activate the", "activate the nox2", "the nox2 complex", "nox2 complex by", "complex by binding", "by binding to", "binding to cybb", "to cybb and", "leading to production", "to production of", "production of superoxide", "of superoxide in", "superoxide in phagosomes", "in phagosomes of", "phagosomes of neutrophils", "of neutrophils which", "neutrophils which is", "which is necessary", "is necessary fo", "necessary fo the", "fo the microbicidal", "the microbicidal activity", "microbicidal activity of", "activity of neutrophils", "neutrophils knaus", "knaus et al.", "et al. 1991", "1991 roberts", "roberts et al.", "et al. 1999", "1999 kim", "kim and dinauer", "and dinauer 2001", "2001 jyoti", "jyoti et al.", "et al. 2014", "al. 2014 .

              nox1", "2014 .

              nox1 complex", "complex composed", "composed of nox1", "nox1 noxa1", "noxa1 noxo1", "noxo1 and cyba", "cyba and", "and nox3 complex", "composed of nox3", "nox3 cyba", "cyba ncf1", "ncf1 amd ncf2", "amd ncf2 or", "ncf2 or noxa1", "noxa1 can", "can also be", "also be activated", "be activated by", "activated by binding", "binding to rac1:gtp", "to rac1:gtp to", "rac1:gtp to produce", "to produce superoxide", "superoxide cheng", "cheng et al.", "et al. 2006", "2006 miyano", "miyano et al.", "2006 ueyama", "ueyama et al.", "al. 2006 .", "nadph oxidases nox", "nox are membrane", "are membrane associated enzymatic", "membrane associated enzymatic complexes", "associated enzymatic complexes that", "enzymatic complexes that use", "complexes that use nadph", "that use nadph as", "use nadph as an", "nadph as an electon", "as an electon donor", "an electon donor to", "electon donor to reduce", "donor to reduce oxygen", "to reduce oxygen and", "reduce oxygen and produce", "oxygen and produce superoxide", "produce superoxide o2", "o2 that", "that serves as a", "serves as a secondary", "as a secondary messenger", "secondary messenger brown", "messenger brown and", "brown and griendling 2009", "and griendling 2009 .

              nox2", "griendling 2009 .

              nox2 complex", "2009 .

              nox2 complex consists", ".

              nox2 complex consists of", "complex consists of cybb", "of cybb nox2", "nox2 cyba", "p22phox ncf1", "p47phox ncf2", "p67phox and ncf4", "and ncf4 p40ohox", "ncf4 p40ohox .", "p40ohox . rac1:gtp binds", ". rac1:gtp binds nox2", "rac1:gtp binds nox2 complex", "binds nox2 complex in", "nox2 complex in response", "complex in response to", "in response to vegf", "response to vegf signaling", "to vegf signaling by", "vegf signaling by directly", "signaling by directly interracting", "by directly interracting with", "directly interracting with cybb", "interracting with cybb and", "with cybb and ncf2", "and ncf2 leading", "ncf2 leading to", "leading to enhancement of", "to enhancement of vegf", "enhancement of vegf signaling", "of vegf signaling through", "vegf signaling through vegf", "signaling through vegf receptor", "through vegf receptor vegfr2", "receptor vegfr2 which", "vegfr2 which plays", "which plays a role", "plays a role in", "a role in angiogenesis", "in angiogenesis price", "angiogenesis price et", "price et al. 2002", "al. 2002 bedard", "2002 bedard and", "bedard and krause 2007", "and krause 2007 .", "krause 2007 . rac2:gtp", "2007 . rac2:gtp can", ". rac2:gtp can also", "rac2:gtp can also activate", "can also activate the", "also activate the nox2", "activate the nox2 complex", "the nox2 complex by", "nox2 complex by binding", "complex by binding to", "by binding to cybb", "binding to cybb and", "to cybb and ncf2", "leading to production of", "to production of superoxide", "production of superoxide in", "of superoxide in phagosomes", "superoxide in phagosomes of", "in phagosomes of neutrophils", "phagosomes of neutrophils which", "of neutrophils which is", "neutrophils which is necessary", "which is necessary fo", "is necessary fo the", "necessary fo the microbicidal", "fo the microbicidal activity", "the microbicidal activity of", "microbicidal activity of neutrophils", "of neutrophils knaus", "neutrophils knaus et", "knaus et al. 1991", "al. 1991 roberts", "1991 roberts et", "roberts et al. 1999", "al. 1999 kim", "1999 kim and", "kim and dinauer 2001", "dinauer 2001 jyoti", "2001 jyoti et", "jyoti et al. 2014", "et al. 2014 .

              nox1", "al. 2014 .

              nox1 complex", ".

              nox1 complex composed", "complex composed of", "of nox1 noxa1", "noxa1 noxo1 and", "and cyba and", "cyba and nox3", "nox3 complex composed", "of nox3 cyba", "cyba ncf1 amd", "ncf1 amd ncf2 or", "amd ncf2 or noxa1", "or noxa1 can", "noxa1 can also", "can also be activated", "also be activated by", "be activated by binding", "activated by binding to", "by binding to rac1:gtp", "binding to rac1:gtp to", "to rac1:gtp to produce", "rac1:gtp to produce superoxide", "produce superoxide cheng", "superoxide cheng et", "cheng et al. 2006", "al. 2006 miyano", "2006 miyano et", "miyano et al. 2006", "al. 2006 ueyama", "2006 ueyama et", "ueyama et al. 2006", "et al. 2006 .", "oxidases nox are", "nox are membrane associated", "are membrane associated enzymatic complexes", "membrane associated enzymatic complexes that", "associated enzymatic complexes that use", "enzymatic complexes that use nadph", "complexes that use nadph as", "that use nadph as an", "use nadph as an electon", "nadph as an electon donor", "as an electon donor to", "an electon donor to reduce", "electon donor to reduce oxygen", "donor to reduce oxygen and", "to reduce oxygen and produce", "reduce oxygen and produce superoxide", "and produce superoxide o2", "o2 that serves", "that serves as a secondary", "serves as a secondary messenger", "a secondary messenger brown", "secondary messenger brown and", "messenger brown and griendling", "brown and griendling 2009 .

              nox2", "and griendling 2009 .

              nox2 complex", "griendling 2009 .

              nox2 complex consists", "2009 .

              nox2 complex consists of", ".

              nox2 complex consists of cybb", "consists of cybb nox2", "ncf2 p67phox and", "and ncf4 p40ohox .", "ncf4 p40ohox . rac1:gtp", "p40ohox . rac1:gtp binds nox2", ". rac1:gtp binds nox2 complex", "rac1:gtp binds nox2 complex in", "binds nox2 complex in response", "nox2 complex in response to", "complex in response to vegf", "in response to vegf signaling", "response to vegf signaling by", "to vegf signaling by directly", "vegf signaling by directly interracting", "signaling by directly interracting with", "by directly interracting with cybb", "directly interracting with cybb and", "interracting with cybb and ncf2", "cybb and ncf2 leading", "and ncf2 leading to", "ncf2 leading to enhancement", "leading to enhancement of vegf", "to enhancement of vegf signaling", "enhancement of vegf signaling through", "of vegf signaling through vegf", "vegf signaling through vegf receptor", "signaling through vegf receptor vegfr2", "vegf receptor vegfr2 which", "receptor vegfr2 which plays", "vegfr2 which plays a", "which plays a role in", "plays a role in angiogenesis", "role in angiogenesis price", "in angiogenesis price et", "angiogenesis price et al.", "et al. 2002 bedard", "al. 2002 bedard and", "2002 bedard and krause", "bedard and krause 2007 .", "and krause 2007 . rac2:gtp", "krause 2007 . rac2:gtp can", "2007 . rac2:gtp can also", ". rac2:gtp can also activate", "rac2:gtp can also activate the", "can also activate the nox2", "also activate the nox2 complex", "activate the nox2 complex by", "the nox2 complex by binding", "nox2 complex by binding to", "complex by binding to cybb", "by binding to cybb and", "binding to cybb and ncf2", "ncf2 leading to production", "leading to production of superoxide", "to production of superoxide in", "production of superoxide in phagosomes", "of superoxide in phagosomes of", "superoxide in phagosomes of neutrophils", "in phagosomes of neutrophils which", "phagosomes of neutrophils which is", "of neutrophils which is necessary", "neutrophils which is necessary fo", "which is necessary fo the", "is necessary fo the microbicidal", "necessary fo the microbicidal activity", "fo the microbicidal activity of", "the microbicidal activity of neutrophils", "activity of neutrophils knaus", "of neutrophils knaus et", "neutrophils knaus et al.", "et al. 1991 roberts", "al. 1991 roberts et", "1991 roberts et al.", "et al. 1999 kim", "al. 1999 kim and", "1999 kim and dinauer", "and dinauer 2001 jyoti", "dinauer 2001 jyoti et", "2001 jyoti et al.", "jyoti et al. 2014 .

              nox1", "et al. 2014 .

              nox1 complex", "2014 .

              nox1 complex composed", ".

              nox1 complex composed of", "complex composed of nox1", "composed of nox1 noxa1", "nox1 noxa1 noxo1", "noxa1 noxo1 and cyba", "noxo1 and cyba and", "and cyba and nox3", "cyba and nox3 complex", "and nox3 complex composed", "nox3 complex composed of", "complex composed of nox3", "composed of nox3 cyba", "nox3 cyba ncf1", "cyba ncf1 amd ncf2", "ncf1 amd ncf2 or noxa1", "ncf2 or noxa1 can", "or noxa1 can also", "noxa1 can also be", "can also be activated by", "also be activated by binding", "be activated by binding to", "activated by binding to rac1:gtp", "by binding to rac1:gtp to", "binding to rac1:gtp to produce", "to rac1:gtp to produce superoxide", "to produce superoxide cheng", "produce superoxide cheng et", "superoxide cheng et al.", "et al. 2006 miyano", "al. 2006 miyano et", "2006 miyano et al.", "et al. 2006 ueyama", "al. 2006 ueyama et", "2006 ueyama et al.", "ueyama et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1443", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5674499", "r hsa", "hsa 5674499", "r hsa 5674499" ] }, { "record_id": "GLY_000594_1_1443", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative feedback", "feedback regulation", "regulation of", "of mapk", "mapk pathway", "negative feedback regulation", "feedback regulation of", "regulation of mapk", "of mapk pathway", "negative feedback regulation of", "feedback regulation of mapk", "regulation of mapk pathway", "negative feedback regulation of mapk", "feedback regulation of mapk pathway", "pathway activation", "activation is", "is limited", "limited by", "by a", "a number", "number of", "of negative", "feedback loops", "loops established", "established by", "by mapk", "mapk dependent", "dependent phosphorylations.", "known substrates", "substrates of", "of activated", "activated mapk", "mapk proteins", "proteins that", "that lie", "lie upstream", "upstream in", "in the", "the raf/mapk", "raf/mapk pathway", "pathway include", "include sos", "and map2k1", "buday et", "et al", "dong et", "dougherty et", "sturm et", "fritsche guenther", "guenther et", "rushworth et", "brummer et", "ritt et", "catalanotti et", "mapk pathway activation", "pathway activation is", "activation is limited", "is limited by", "limited by a", "by a number", "a number of", "number of negative", "of negative feedback", "negative feedback loops", "feedback loops established", "loops established by", "established by mapk", "by mapk dependent", "mapk dependent phosphorylations.", "phosphorylations. known", "known substrates of", "substrates of activated", "of activated mapk", "activated mapk proteins", "mapk proteins that", "proteins that lie", "that lie upstream", "lie upstream in", "upstream in the", "in the raf/mapk", "the raf/mapk pathway", "raf/mapk pathway include", "pathway include sos", "sos raf1", "raf1 braf", "braf and", "map2k1 buday", "buday et al", "al 1995", "1995 dong", "dong et al", "al 1996", "1996 dougherty", "dougherty et al", "al 2005", "2005 sturm", "sturm et al", "al 2010", "2010 fritsche", "fritsche guenther et", "guenther et al", "al 2011", "2011 rushworth", "rushworth et al", "al 2006", "2006 brummer", "brummer et al", "al 2003", "2003 ritt", "ritt et al", "2010 catalanotti", "catalanotti et al", "al 2009", "mapk pathway activation is", "pathway activation is limited", "activation is limited by", "is limited by a", "limited by a number", "by a number of", "a number of negative", "number of negative feedback", "of negative feedback loops", "negative feedback loops established", "feedback loops established by", "loops established by mapk", "established by mapk dependent", "by mapk dependent phosphorylations.", "dependent phosphorylations. known", "phosphorylations. known substrates", "known substrates of activated", "substrates of activated mapk", "of activated mapk proteins", "activated mapk proteins that", "mapk proteins that lie", "proteins that lie upstream", "that lie upstream in", "lie upstream in the", "upstream in the raf/mapk", "in the raf/mapk pathway", "the raf/mapk pathway include", "raf/mapk pathway include sos", "include sos raf1", "braf and map2k1", "and map2k1 buday", "map2k1 buday et", "et al 1995", "1995 dong et", "et al 1996", "1996 dougherty et", "et al 2005", "2005 sturm et", "et al 2010", "2010 fritsche guenther", "fritsche guenther et al", "et al 2011", "2011 rushworth et", "et al 2006", "2006 brummer et", "et al 2003", "2003 ritt et", "2010 catalanotti et", "et al 2009", "mapk pathway activation is limited", "pathway activation is limited by", "activation is limited by a", "is limited by a number", "limited by a number of", "by a number of negative", "a number of negative feedback", "number of negative feedback loops", "of negative feedback loops established", "negative feedback loops established by", "feedback loops established by mapk", "loops established by mapk dependent", "established by mapk dependent phosphorylations.", "mapk dependent phosphorylations. known", "dependent phosphorylations. known substrates", "phosphorylations. known substrates of", "known substrates of activated mapk", "substrates of activated mapk proteins", "of activated mapk proteins that", "activated mapk proteins that lie", "mapk proteins that lie upstream", "proteins that lie upstream in", "that lie upstream in the", "lie upstream in the raf/mapk", "upstream in the raf/mapk pathway", "in the raf/mapk pathway include", "the raf/mapk pathway include sos", "pathway include sos raf1", "sos raf1 braf", "raf1 braf and", "and map2k1 buday et", "map2k1 buday et al", "buday et al 1995", "al 1995 dong", "1995 dong et al", "dong et al 1996", "al 1996 dougherty", "1996 dougherty et al", "dougherty et al 2005", "al 2005 sturm", "2005 sturm et al", "sturm et al 2010", "al 2010 fritsche", "2010 fritsche guenther et", "guenther et al 2011", "al 2011 rushworth", "2011 rushworth et al", "rushworth et al 2006", "al 2006 brummer", "2006 brummer et al", "brummer et al 2003", "al 2003 ritt", "2003 ritt et al", "ritt et al 2010", "al 2010 catalanotti", "2010 catalanotti et al", "catalanotti et al 2009" ] }, { "record_id": "GLY_000594_1_1444", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5675482", "r hsa", "hsa 5675482", "r hsa 5675482" ] }, { "record_id": "GLY_000594_1_1444", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of necroptotic", "necroptotic cell", "cell death", "regulation of necroptotic", "of necroptotic cell", "necroptotic cell death", "regulation of necroptotic cell", "of necroptotic cell death", "regulation of necroptotic cell death", "a regulated", "regulated balance", "balance between", "between cell", "cell survival", "survival and", "and cell", "death is", "is essential", "essential for", "for normal", "normal development", "development 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"contribute to autoimmune disease", "autoimmune disease neurodegeneration", "neurodegeneration ischemia/reperfusion injury", "ischemia/reperfusion injury non", "injury non alcoholic", "alcoholic steatohepatitis nash", "nash and cancer.", "a regulated balance between cell", "regulated balance between cell survival", "balance between cell survival and", "between cell survival and cell", "cell survival and cell death", "survival and cell death is", "and cell death is essential", "cell death is essential for", "death is essential for normal", "is essential for normal development", "essential for normal development and", "for normal development and homeostasis", "normal development and homeostasis of", "development and homeostasis of multicellular", "and homeostasis of multicellular organisms.", "homeostasis of multicellular organisms. defects", "of multicellular organisms. defects in", "multicellular organisms. defects in control", "organisms. defects in control of", "defects in control of this", "in control of this balance", "control of this balance may", "of this balance may contribute", "this balance may contribute to", "balance may contribute to autoimmune", "may contribute to autoimmune disease", "to autoimmune disease neurodegeneration", "disease neurodegeneration ischemia/reperfusion", "ischemia/reperfusion injury non alcoholic", "injury non alcoholic steatohepatitis", "non alcoholic steatohepatitis nash", "steatohepatitis nash and" ] }, { "record_id": "GLY_000594_1_1445", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5676934", "r hsa", "hsa 5676934", "r hsa 5676934" ] }, { "record_id": "GLY_000594_1_1445", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "protein repair", "reactive oxygen", "oxygen species", "such as", "as h2o2", "superoxide anions", "anions and", "and hydroxyl", "hydroxyl radicals", "radicals interact", "interact with", "with molecules", "molecules in", "in the", "the cell", "cell causing", "causing damage", "damage that", "that impairs", "impairs cellular", "cellular functions.", "functions. although", "although cells", "cells have", "have mechanisms", "mechanisms to", "to destroy", "destroy ros", "ros and", "and repair", "repair the", "the damage", "damage caused", "caused by", "by ros", "it is", "is considered", "considered to", "to be", "be a", "a major", "major factor", "factor in", "in age", "age related", "related diseases", "diseases and", "and the", "the ageing", "ageing process", "zhang &", "& weissbach", "weissbach 2008", "kim et", "et al.", "al. 2014", "2014 .", ". ros", "ros scavenging", "scavenging systems", "systems include", "include enzymes", "enzymes such", "as peroxiredoxins", "superoxide dismutases", "catalases and", "and glutathione", "glutathione peroxidases", "peroxidases exist", "exist to", "to minimise", "minimise the", "the potential", "potential damage.", "damage.

              ros", "

              ros reactions", "reactions can", "can also", "also cause", "cause specific", "specific modifications", "modifications to", "to amino", "amino acid", "acid side", "side chains", "chains that", "that result", "result in", "in structural", "structural changes", "changes to", "to proteins/enzymes.", "proteins/enzymes. methionine", "and cysteine", "can be", "be oxidised", "oxidised by", "ros to", "to sulfoxide", "sulfoxide and", "and further", "further oxidised", "oxidised to", "to sulfone", "sulfone derivatives.", "derivatives. both", "both free", "free met", "met and", "and protein", "protein based", "based met", "met are", "are readily", "readily oxidized", "oxidized to", "to form", "form methionine", "methionine sulphoxide", "brot &", "weissbach 1991", "1991 .", ". many", "many proteins", "proteins have", "have been", "been demonstrated", "demonstrated to", "to undergo", "undergo such", "such oxidation", "oxidation and", "and as", "as a", "a consequence", "consequence have", "have altered", "altered function", "levine et", "al. 2000", "2000 .", ". sulphoxide", "sulphoxide formation", "formation can", "be reversed", "reversed by", "by the", "the action", "action of", "of the", "the methionine", "sulphoxide reductase", "reductase system", "which catalyses", "catalyses the", "the reduction", "reduction of", "of meto", "meto to", "to met", "brot et", "al. 1981", "1981 .", ". this", "this repair", "repair uses", "uses one", "one ros", "ros equivalent", "so msr", "msr proteins", "proteins can", "can act", "act as", "as catalytic", "catalytic antioxidants", "removing ros", "al. 1996", "1996 .", ". methionine", "methionine oxidation", "oxidation results", "results in", "in a", "a mixture", "mixture of", "of methionine", "s oxides", "oxides of", "diastereomers which", "which are", "are reduced", "reduced by", "by msra", "msra and", "and msrb", "respectively. msra", "msra can", "can reduce", "reduce both", "free and", "based methionine", "s oxide", "whereas msrb", "msrb is", "is specific", "specific for", "for protein", "s oxide.", "oxide. mammals", "mammals typically", "typically have", "have only", "only one", "one gene", "gene encoding", "encoding msra", "but at", "at least", "least three", "three genes", "genes encoding", "encoding msrbs", "hansel et", "al. 2005", "2005 .", ". although", "although structurally", "structurally distinct", "mrsa and", "and mrsb", "mrsb share", "share a", "a common", "common three", "three step", "step catalytic", "catalytic mechanism.", "mechanism. in", "the first", "first step", "the msr", "msr catalytic", "catalytic cysteine", "cysteine residue", "residue interacts", "interacts with", "with the", "the meto", "meto substrate", "which leads", "leads to", "to product", "product release", "release and", "and formation", "formation of", "the sulfenic", "sulfenic acid.", "acid. in", "the second", "second step", "an intramolecular", "intramolecular disulfide", "disulfide bridge", "bridge is", "is formed", "formed between", "between the", "the catalytic", "cysteine and", "the regenerating", "regenerating cysteine.", "cysteine. in", "the final", "final step", "the disulfide", "is reduced", "by an", "an electron", "electron donor", "the nadph", "nadph dependent", "dependent thioredoxin/tr", "thioredoxin/tr system", "leading to", "to the", "the regeneration", "regeneration of", "msr active", "active site", "boschi muller", "muller et", "al. 2008", "2008 .

              beta", ".

              beta linked", "linked isoaspartyl", "peptide bonds", "bonds can", "can arise", "arise spontaneously", "spontaneously via", "via succinimide", "succinimide linked", "linked deamidation", "deamidation of", "of asparagine", "or dehydration", "dehydration of", "of aspartate", "asp .", ". protein", "protein l", "l isoaspartate", "d aspartate", "o methyltransferase", "pimt ec", "ec 2.1.1.77", "transfers the", "the methyl", "methyl group", "group from", "from s", "s adenosyl", "adenosyl l", "l methionine", "the alpha", "alpha side", "side chain", "chain carboxyl", "carboxyl group", "group of", "of l", "l isoaspartyl", "isoaspartyl and", "and d", "d aspartatyl", "aspartatyl amino", "amino acids.", "acids. the", "the resulting", "resulting methyl", "methyl ester", "ester undergoes", "undergoes spontaneous", "spontaneous transformation", "transformation to", "to l", "l succinimide", "which spontaneously", "spontaneously hydrolyses", "hydrolyses to", "to generates", "generates l", "l aspartyl", "aspartyl residues", "residues or", "or l", "isoaspartyl residues", "knorre et", "al. 2009", "2009 .", "repair process", "process helps", "helps to", "to maintain", "maintain overall", "overall protein", "protein integrity.", "reactive oxygen species", "species ros", "ros such", "such as h2o2", "h2o2 superoxide", "superoxide anions and", "anions and hydroxyl", "and hydroxyl radicals", "hydroxyl radicals interact", "radicals interact with", "interact with molecules", "with molecules in", "molecules in the", "in the cell", "the cell causing", "cell causing damage", "causing damage that", "damage that impairs", "that impairs cellular", "impairs cellular functions.", "cellular functions. although", "functions. although cells", "although cells have", "cells have mechanisms", "have mechanisms to", "mechanisms to destroy", "to destroy ros", "destroy ros and", "ros and repair", "and repair the", "repair the damage", "the damage caused", "damage caused by", "caused by ros", "ros it", "it is considered", "is considered to", "considered to be", "to be a", "be a major", "a major factor", "major factor in", "factor in age", "in age related", "age related diseases", "related diseases and", "diseases and the", "and the ageing", "the ageing process", "process zhang", "zhang & weissbach", "& weissbach 2008", "2008 kim", "kim et al.", "et al. 2014", "al. 2014 .", "2014 . ros", ". ros scavenging", "ros scavenging systems", "scavenging systems include", "systems include enzymes", "include enzymes such", "enzymes such as", "such as peroxiredoxins", "peroxiredoxins superoxide", "dismutases catalases", "catalases and glutathione", "and glutathione peroxidases", "glutathione peroxidases exist", "peroxidases exist to", "exist to minimise", "to minimise the", "minimise the potential", "the potential damage.", "potential damage.

              ros", "damage.

              ros reactions", "

              ros reactions can", "reactions can also", "can also cause", "also cause specific", "cause specific modifications", "specific modifications to", "modifications to amino", "to amino acid", "amino acid side", "acid side chains", "side chains that", "chains that result", "that result in", "result in structural", "in structural changes", "structural changes to", "changes to proteins/enzymes.", "to proteins/enzymes. methionine", "methionine met", "cysteine cys", "cys can", "can be oxidised", "be oxidised by", "oxidised by ros", "by ros to", "ros to sulfoxide", "to sulfoxide and", "sulfoxide and further", "and further oxidised", "further oxidised to", "oxidised to sulfone", "to sulfone derivatives.", "sulfone derivatives. both", "derivatives. both free", "both free met", "free met and", "met and protein", "and protein based", "protein based met", "based met are", "met are readily", "are readily oxidized", "readily oxidized to", "oxidized to form", "to form methionine", "form methionine sulphoxide", "sulphoxide meto", "brot & weissbach", "& weissbach 1991", "weissbach 1991 .", "1991 . many", ". many proteins", "many proteins have", "proteins have been", "have been demonstrated", "been demonstrated to", "demonstrated to undergo", "to undergo such", "undergo such oxidation", "such oxidation and", "oxidation and as", "and as a", "as a consequence", "a consequence have", "consequence have altered", "have altered function", "function levine", "levine et al.", "et al. 2000", "al. 2000 .", "2000 . sulphoxide", ". sulphoxide formation", "sulphoxide formation can", "formation can be", "can be reversed", "be reversed by", "reversed by the", "by the action", "the action of", "action of the", "of the methionine", "the methionine sulphoxide", "methionine sulphoxide reductase", "sulphoxide reductase system", "system msr", "msr which", "which catalyses the", "catalyses the reduction", "the reduction of", "reduction of meto", "of meto to", "meto to met", "met brot", "brot et al.", "et al. 1981", "al. 1981 .", "1981 . this", ". this repair", "this repair uses", "repair uses one", "uses one ros", "one ros equivalent", "equivalent so", "so msr proteins", "msr proteins can", "proteins can act", "can act as", "act as catalytic", "as catalytic antioxidants", "antioxidants removing", "ros levine", "et al. 1996", "al. 1996 .", "1996 . methionine", ". methionine oxidation", "methionine oxidation results", "oxidation results in", "results in a", "in a mixture", "a mixture of", "mixture of methionine", "methionine s", "s s", "s and", "and r", "r s", "s oxides of", "oxides of methionine", "methionine diastereomers", "diastereomers which are", "which are reduced", "are reduced by", "reduced by msra", "by msra and", "msra and msrb", "msrb respectively.", "respectively. msra can", "msra can reduce", "can reduce both", "reduce both free", "both free and", "free and protein", "protein based methionine", "oxide whereas", "whereas msrb is", "msrb is specific", "is specific for", "specific for protein", "for protein based", "methionine r", "s oxide. mammals", "oxide. mammals typically", "mammals typically have", "typically have only", "have only one", "only one gene", "one gene encoding", "gene encoding msra", "msra but", "but at least", "at least three", "least three genes", "three genes encoding", "genes encoding msrbs", "msrbs hansel", "hansel et al.", "et al. 2005", "al. 2005 .", "2005 . although", ". although structurally", "although structurally distinct", "distinct mrsa", "mrsa and mrsb", "and mrsb share", "mrsb share a", "share a common", "a common three", "common three step", "three step catalytic", "step catalytic mechanism.", "catalytic mechanism. in", "mechanism. in the", "in the first", "the first step", "step the", "the msr catalytic", "msr catalytic cysteine", "catalytic cysteine residue", "cysteine residue interacts", "residue interacts with", "interacts with the", "with the meto", "the meto substrate", "substrate which", "which leads to", "leads to product", "to product release", "product release and", "release and formation", "and formation of", "formation of the", "of the sulfenic", "the sulfenic acid.", "sulfenic acid. in", "acid. in the", "in the second", "the second step", "step an", "an intramolecular disulfide", "intramolecular disulfide bridge", "disulfide bridge is", "bridge is formed", "is formed between", "formed between the", "between the catalytic", "the catalytic cysteine", "catalytic cysteine and", "cysteine and the", "and the regenerating", "the regenerating cysteine.", "regenerating cysteine. in", "cysteine. in the", "in the final", "the final step", "the disulfide bridge", "bridge is reduced", "is reduced by", "reduced by an", "by an electron", "an electron donor", "donor the", "the nadph dependent", "nadph dependent thioredoxin/tr", "dependent thioredoxin/tr system", "system leading", "leading to the", "to the regeneration", "the regeneration of", "regeneration of the", "of the msr", "the msr active", "msr active site", "site boschi", "boschi muller et", "muller et al.", "et al. 2008", "al. 2008 .

              beta", "2008 .

              beta linked", ".

              beta linked isoaspartyl", "isoaspartyl isoasp", "isoasp peptide", "peptide bonds can", "bonds can arise", "can arise spontaneously", "arise spontaneously via", "spontaneously via succinimide", "via succinimide linked", "succinimide linked deamidation", "linked deamidation of", "deamidation of asparagine", "asparagine asn", "asn or", "or dehydration of", "dehydration of aspartate", "aspartate asp", "asp . protein", ". protein l", "protein l isoaspartate", "isoaspartate d", "aspartate o", "methyltransferase pcmt1", "pcmt1 pimt", "pimt ec 2.1.1.77", "2.1.1.77 transfers", "transfers the methyl", "the methyl group", "methyl group from", "group from s", "from s adenosyl", "s adenosyl l", "adenosyl l methionine", "methionine adomet", "adomet to", "to the alpha", "the alpha side", "alpha side chain", "side chain carboxyl", "chain carboxyl group", "carboxyl group of", "group of l", "of l isoaspartyl", "l isoaspartyl and", "isoaspartyl and d", "and d aspartatyl", "d aspartatyl amino", "aspartatyl amino acids.", "amino acids. the", "acids. the resulting", "the resulting methyl", "resulting methyl ester", "methyl ester undergoes", "ester undergoes spontaneous", "undergoes spontaneous transformation", "spontaneous transformation to", "transformation to l", "to l succinimide", "succinimide which", "which spontaneously hydrolyses", "spontaneously hydrolyses to", "hydrolyses to generates", "to generates l", "generates l aspartyl", "l aspartyl residues", "aspartyl residues or", "residues or l", "or l isoaspartyl", "l isoaspartyl residues", "residues knorre", "knorre et al.", "et al. 2009", "al. 2009 .", "2009 . this", "this repair process", "repair process helps", "process helps to", "helps to maintain", "to maintain overall", "maintain overall protein", "overall protein integrity.", "oxygen species ros", "ros such as", "as h2o2 superoxide", "h2o2 superoxide anions", "superoxide anions and hydroxyl", "anions and hydroxyl radicals", "and hydroxyl radicals interact", "hydroxyl radicals interact with", "radicals interact with molecules", "interact with molecules in", "with molecules in the", "molecules in the cell", "in the cell causing", "the cell causing damage", "cell causing damage that", "causing damage that impairs", "damage that impairs cellular", "that impairs cellular functions.", "impairs cellular functions. although", "cellular functions. although cells", "functions. although cells have", "although cells have mechanisms", "cells have mechanisms to", "have mechanisms to destroy", "mechanisms to destroy ros", "to destroy ros and", "destroy ros and repair", "ros and repair the", "and repair the damage", "repair the damage caused", "the damage caused by", "damage caused by ros", "by ros it", "ros it is", "it is considered to", "is considered to be", "considered to be a", "to be a major", "be a major factor", "a major factor in", "major factor in age", "factor in age related", "in age related diseases", "age related diseases and", "related diseases and the", "diseases and the ageing", "and the ageing process", "ageing process zhang", "process zhang &", "zhang & weissbach 2008", "weissbach 2008 kim", "2008 kim et", "kim et al. 2014", "et al. 2014 .", "al. 2014 . ros", "2014 . ros scavenging", ". ros scavenging systems", "ros scavenging systems include", "scavenging systems include enzymes", "systems include enzymes such", "include enzymes such as", "enzymes such as peroxiredoxins", "as peroxiredoxins superoxide", "peroxiredoxins superoxide dismutases", "superoxide dismutases catalases", "dismutases catalases and", "catalases and glutathione peroxidases", "and glutathione peroxidases exist", "glutathione peroxidases exist to", "peroxidases exist to minimise", "exist to minimise the", "to minimise the potential", "minimise the potential damage.", "the potential damage.

              ros", "potential damage.

              ros reactions", "damage.

              ros reactions can", "

              ros reactions can also", "reactions can also cause", "can also cause specific", "also cause specific modifications", "cause specific modifications to", "specific modifications to amino", "modifications to amino acid", "to amino acid side", "amino acid side chains", "acid side chains that", "side chains that result", "chains that result in", "that result in structural", "result in structural changes", "in structural changes to", "structural changes to proteins/enzymes.", "changes to proteins/enzymes. methionine", "proteins/enzymes. methionine met", "met and cysteine", "and cysteine cys", "cys can be", "can be oxidised by", "be oxidised by ros", "oxidised by ros to", "by ros to sulfoxide", "ros to sulfoxide and", "to sulfoxide and further", "sulfoxide and further oxidised", "and further oxidised to", "further oxidised to sulfone", "oxidised to sulfone derivatives.", "to sulfone derivatives. both", "sulfone derivatives. both free", "derivatives. both free met", "both free met and", "free met and protein", "met and protein based", "and protein based met", "protein based met are", "based met are readily", "met are readily oxidized", "are readily oxidized to", "readily oxidized to form", "oxidized to form methionine", "to form methionine sulphoxide", "methionine sulphoxide meto", "meto brot", "brot & weissbach 1991", "& weissbach 1991 .", "weissbach 1991 . many", "1991 . many proteins", ". many proteins have", "many proteins have been", "proteins have been demonstrated", "have been demonstrated to", "been demonstrated to undergo", "demonstrated to undergo such", "to undergo such oxidation", "undergo such oxidation and", "such oxidation and as", "oxidation and as a", "and as a consequence", "as a consequence have", "a consequence have altered", "consequence have altered function", "altered function levine", "function levine et", "levine et al. 2000", "et al. 2000 .", "al. 2000 . sulphoxide", "2000 . sulphoxide formation", ". sulphoxide formation can", "sulphoxide formation can be", "formation can be reversed", "can be reversed by", "be reversed by the", "reversed by the action", "by the action of", "the action of the", "action of the methionine", "of the methionine sulphoxide", "the methionine sulphoxide reductase", "methionine sulphoxide reductase system", "reductase system msr", "msr which catalyses", "which catalyses the reduction", "catalyses the reduction of", "the reduction of meto", "reduction of meto to", "of meto to met", "to met brot", "met brot et", "brot et al. 1981", "et al. 1981 .", "al. 1981 . this", "1981 . this repair", ". this repair uses", "this repair uses one", "repair uses one ros", "uses one ros equivalent", "ros equivalent so", "equivalent so msr", "so msr proteins can", "msr proteins can act", "proteins can act as", "can act as catalytic", "act as catalytic antioxidants", "catalytic antioxidants removing", "antioxidants removing ros", "removing ros levine", "ros levine et", "levine et al. 1996", "et al. 1996 .", "al. 1996 . methionine", "1996 . methionine oxidation", ". methionine oxidation results", "methionine oxidation results in", "oxidation results in a", "results in a mixture", "in a mixture of", "a mixture of methionine", "of methionine s", "r s oxides", "s oxides of methionine", "of methionine diastereomers", "methionine diastereomers which", "diastereomers which are reduced", "which are reduced by", "are reduced by msra", "reduced by msra and", "by msra and msrb", "and msrb respectively.", "msrb respectively. msra", "respectively. msra can reduce", "msra can reduce both", "can reduce both free", "reduce both free and", "both free and protein", "free and protein based", "and protein based methionine", "based methionine s", "s s oxide", "s oxide whereas", "oxide whereas msrb", "whereas msrb is specific", "msrb is specific for", "is specific for protein", "specific for protein based", "for protein based methionine", "based methionine r", "r s oxide.", "s oxide. mammals typically", "oxide. mammals typically have", "mammals typically have only", "typically have only one", "have only one gene", "only one gene encoding", "one gene encoding msra", "encoding msra but", "msra but at", "but at least three", "at least three genes", "least three genes encoding", "three genes encoding msrbs", "encoding msrbs hansel", "msrbs hansel et", "hansel et al. 2005", "et al. 2005 .", "al. 2005 . although", "2005 . although structurally", ". although structurally distinct", "structurally distinct mrsa", "distinct mrsa and", "mrsa and mrsb share", "and mrsb share a", "mrsb share a common", "share a common three", "a common three step", "common three step catalytic", "three step catalytic mechanism.", "step catalytic mechanism. in", "catalytic mechanism. in the", "mechanism. in the first", "in the first step", "first step the", "step the msr", "the msr catalytic cysteine", "msr catalytic cysteine residue", "catalytic cysteine residue interacts", "cysteine residue interacts with", "residue interacts with the", "interacts with the meto", "with the meto substrate", "meto substrate which", "substrate which leads", "which leads to product", "leads to product release", "to product release and", "product release and formation", "release and formation of", "and formation of the", "formation of the sulfenic", "of the sulfenic acid.", "the sulfenic acid. in", "sulfenic acid. in the", "acid. in the second", "in the second step", "second step an", "step an intramolecular", "an intramolecular disulfide bridge", "intramolecular disulfide bridge is", "disulfide bridge is formed", "bridge is formed between", "is formed between the", "formed between the catalytic", "between the catalytic cysteine", "the catalytic cysteine and", "catalytic cysteine and the", "cysteine and the regenerating", "and the regenerating cysteine.", "the regenerating cysteine. in", "regenerating cysteine. in the", "cysteine. in the final", "in the final step", "final step the", "step the disulfide", "the disulfide bridge is", "disulfide bridge is reduced", "bridge is reduced by", "is reduced by an", "reduced by an electron", "by an electron donor", "electron donor the", "donor the nadph", "the nadph dependent thioredoxin/tr", "nadph dependent thioredoxin/tr system", "thioredoxin/tr system leading", "system leading to", "leading to the regeneration", "to the regeneration of", "the regeneration of the", "regeneration of the msr", "of the msr active", "the msr active site", "active site boschi", "site boschi muller", "boschi muller et al.", "muller et al. 2008", "et al. 2008 .

              beta", "al. 2008 .

              beta linked", "2008 .

              beta linked isoaspartyl", "linked isoaspartyl isoasp", "isoasp peptide bonds", "peptide bonds can arise", "bonds can arise spontaneously", "can arise spontaneously via", "arise spontaneously via succinimide", "spontaneously via succinimide linked", "via succinimide linked deamidation", "succinimide linked deamidation of", "linked deamidation of asparagine", "of asparagine asn", "asn or dehydration", "or dehydration of aspartate", "of aspartate asp", "aspartate asp .", "asp . protein l", ". protein l isoaspartate", "l isoaspartate d", "isoaspartate d aspartate", "d aspartate o", "aspartate o methyltransferase", "o methyltransferase pcmt1", "pcmt1 pimt ec", "ec 2.1.1.77 transfers", "2.1.1.77 transfers the", "transfers the methyl group", "the methyl group from", "methyl group from s", "group from s adenosyl", "from s adenosyl l", "s adenosyl l methionine", "l methionine adomet", "adomet to the", "to the alpha side", "the alpha side chain", "alpha side chain carboxyl", "side chain carboxyl group", "chain carboxyl group of", "carboxyl group of l", "group of l isoaspartyl", "of l isoaspartyl and", "l isoaspartyl and d", "isoaspartyl and d aspartatyl", "and d aspartatyl amino", "d aspartatyl amino acids.", "aspartatyl amino acids. the", "amino acids. the resulting", "acids. the resulting methyl", "the resulting methyl ester", "resulting methyl ester undergoes", "methyl ester undergoes spontaneous", "ester undergoes spontaneous transformation", "undergoes spontaneous transformation to", "spontaneous transformation to l", "transformation to l succinimide", "l succinimide which", "succinimide which spontaneously", "which spontaneously hydrolyses to", "spontaneously hydrolyses to generates", "hydrolyses to generates l", "to generates l aspartyl", "generates l aspartyl residues", "l aspartyl residues or", "aspartyl residues or l", "residues or l isoaspartyl", "or l isoaspartyl residues", "isoaspartyl residues knorre", "residues knorre et", "knorre et al. 2009", "et al. 2009 .", "al. 2009 . this", "2009 . this repair", ". this repair process", "this repair process helps", "repair process helps to", "process helps to maintain", "helps to maintain overall", "to maintain overall protein", "maintain overall protein integrity.", "reactive oxygen species ros", "species ros such", "ros such as h2o2", "such as h2o2 superoxide", "as h2o2 superoxide anions", "h2o2 superoxide anions and", "superoxide anions and hydroxyl radicals", "anions and hydroxyl radicals interact", "and hydroxyl radicals interact with", "hydroxyl radicals interact with molecules", "radicals interact with molecules in", "interact with molecules in the", "with molecules in the cell", "molecules in the cell causing", "in the cell causing damage", "the cell causing damage that", "cell causing damage that impairs", "causing damage that impairs cellular", "damage that impairs cellular functions.", "that impairs cellular functions. although", "impairs cellular functions. although cells", "cellular functions. although cells have", "functions. although cells have mechanisms", "although cells have mechanisms to", "cells have mechanisms to destroy", "have mechanisms to destroy ros", "mechanisms to destroy ros and", "to destroy ros and repair", "destroy ros and repair the", "ros and repair the damage", "and repair the damage caused", "repair the damage caused by", "the damage caused by ros", "caused by ros it", "by ros it is", "ros it is considered", "it is considered to be", "is considered to be a", "considered to be a major", "to be a major factor", "be a major factor in", "a major factor in age", "major factor in age related", "factor in age related diseases", "in age related diseases and", "age related diseases and the", "related diseases and the ageing", "diseases and the ageing process", "the ageing process zhang", "ageing process zhang &", "process zhang & weissbach", "& weissbach 2008 kim", "weissbach 2008 kim et", "2008 kim et al.", "kim et al. 2014 .", "et al. 2014 . ros", "al. 2014 . ros scavenging", "2014 . ros scavenging systems", ". ros scavenging systems include", "ros scavenging systems include enzymes", "scavenging systems include enzymes such", "systems include enzymes such as", "include enzymes such as peroxiredoxins", "such as peroxiredoxins superoxide", "as peroxiredoxins superoxide dismutases", "superoxide dismutases catalases and", "dismutases catalases and glutathione", "catalases and glutathione peroxidases exist", "and glutathione peroxidases exist to", "glutathione peroxidases exist to minimise", "peroxidases exist to minimise the", "exist to minimise the potential", "to minimise the potential damage.", "minimise the potential damage.

              ros", "the potential damage.

              ros reactions", "potential damage.

              ros reactions can", "damage.

              ros reactions can also", "

              ros reactions can also cause", "reactions can also cause specific", "can also cause specific modifications", "also cause specific modifications to", "cause specific modifications to amino", "specific modifications to amino acid", "modifications to amino acid side", "to amino acid side chains", "amino acid side chains that", "acid side chains that result", "side chains that result in", "chains that result in structural", "that result in structural changes", "result in structural changes to", "in structural changes to proteins/enzymes.", "structural changes to proteins/enzymes. methionine", "to proteins/enzymes. methionine met", "methionine met and", "cysteine cys can", "cys can be oxidised", "can be oxidised by ros", "be oxidised by ros to", "oxidised by ros to sulfoxide", "by ros to sulfoxide and", "ros to sulfoxide and further", "to sulfoxide and further oxidised", "sulfoxide and further oxidised to", "and further oxidised to sulfone", "further oxidised to sulfone derivatives.", "oxidised to sulfone derivatives. both", "to sulfone derivatives. both free", "sulfone derivatives. both free met", "derivatives. both free met and", "both free met and protein", "free met and protein based", "met and protein based met", "and protein based met are", "protein based met are readily", "based met are readily oxidized", "met are readily oxidized to", "are readily oxidized to form", "readily oxidized to form methionine", "oxidized to form methionine sulphoxide", "form methionine sulphoxide meto", "meto brot &", "brot & weissbach 1991 .", "& weissbach 1991 . many", "weissbach 1991 . many proteins", "1991 . many proteins have", ". many proteins have been", "many proteins have been demonstrated", "proteins have been demonstrated to", "have been demonstrated to undergo", "been demonstrated to undergo such", "demonstrated to undergo such oxidation", "to undergo such oxidation and", "undergo such oxidation and as", "such oxidation and as a", "oxidation and as a consequence", "and as a consequence have", "as a consequence have altered", "a consequence have altered function", "have altered function levine", "altered function levine et", "function levine et al.", "levine et al. 2000 .", "et al. 2000 . sulphoxide", "al. 2000 . sulphoxide formation", "2000 . sulphoxide formation can", ". sulphoxide formation can be", "sulphoxide formation can be reversed", "formation can be reversed by", "can be reversed by the", "be reversed by the action", "reversed by the action of", "by the action of the", "the action of the methionine", "action of the methionine sulphoxide", "of the methionine sulphoxide reductase", "the methionine sulphoxide reductase system", "sulphoxide reductase system msr", "system msr which", "msr which catalyses the", "which catalyses the reduction of", "catalyses the reduction of meto", "the reduction of meto to", "reduction of meto to met", "meto to met brot", "to met brot et", "met brot et al.", "brot et al. 1981 .", "et al. 1981 . this", "al. 1981 . this repair", "1981 . this repair uses", ". this repair uses one", "this repair uses one ros", "repair uses one ros equivalent", "one ros equivalent so", "ros equivalent so msr", "equivalent so msr proteins", "so msr proteins can act", "msr proteins can act as", "proteins can act as catalytic", "can act as catalytic antioxidants", "as catalytic antioxidants removing", "catalytic antioxidants removing ros", "removing ros levine et", "ros levine et al.", "levine et al. 1996 .", "et al. 1996 . methionine", "al. 1996 . methionine oxidation", "1996 . methionine oxidation results", ". methionine oxidation results in", "methionine oxidation results in a", "oxidation results in a mixture", "results in a mixture of", "in a mixture of methionine", "mixture of methionine s", "methionine s s", "s s and", "s and r", "and r s", "r s oxides of", "oxides of methionine diastereomers", "of methionine diastereomers which", "methionine diastereomers which are", "diastereomers which are reduced by", "which are reduced by msra", "are reduced by msra and", "reduced by msra and msrb", "msra and msrb respectively.", "and msrb respectively. msra", "msrb respectively. msra can", "respectively. msra can reduce both", "msra can reduce both free", "can reduce both free and", "reduce both free and protein", "both free and protein based", "free and protein based methionine", "protein based methionine s", "s oxide whereas msrb", "oxide whereas msrb is", "whereas msrb is specific for", "msrb is specific for protein", "is specific for protein based", "specific for protein based methionine", "protein based methionine r", "methionine r s", "r s oxide. mammals", "s oxide. mammals typically have", "oxide. mammals typically have only", "mammals typically have only one", "typically have only one gene", "have only one gene encoding", "only one gene encoding msra", "gene encoding msra but", "encoding msra but at", "msra but at least", "but at least three genes", "at least three genes encoding", "least three genes encoding msrbs", "genes encoding msrbs hansel", "encoding msrbs hansel et", "msrbs hansel et al.", "hansel et al. 2005 .", "et al. 2005 . although", "al. 2005 . although structurally", "2005 . although structurally distinct", "although structurally distinct mrsa", "structurally distinct mrsa and", "distinct mrsa and mrsb", "mrsa and mrsb share a", "and mrsb share a common", "mrsb share a common three", "share a common three step", "a common three step catalytic", "common three step catalytic mechanism.", "three step catalytic mechanism. in", "step catalytic mechanism. in the", "catalytic mechanism. in the first", "mechanism. in the first step", "the first step the", "first step the msr", "step the msr catalytic", "the msr catalytic cysteine residue", "msr catalytic cysteine residue interacts", "catalytic cysteine residue interacts with", "cysteine residue interacts with the", "residue interacts with the meto", "interacts with the meto substrate", "the meto substrate which", "meto substrate which leads", "substrate which leads to", "which leads to product release", "leads to product release and", "to product release and formation", "product release and formation of", "release and formation of the", "and formation of the sulfenic", "formation of the sulfenic acid.", "of the sulfenic acid. in", "the sulfenic acid. in the", "sulfenic acid. in the second", "acid. in the second step", "the second step an", "second step an intramolecular", "step an intramolecular disulfide", "an intramolecular disulfide bridge is", "intramolecular disulfide bridge is formed", "disulfide bridge is formed between", "bridge is formed between the", "is formed between the catalytic", "formed between the catalytic cysteine", "between the catalytic cysteine and", "the catalytic cysteine and the", "catalytic cysteine and the regenerating", "cysteine and the regenerating cysteine.", "and the regenerating cysteine. in", "the regenerating cysteine. in the", "regenerating cysteine. in the final", "cysteine. in the final step", "the final step the", "final step the disulfide", "step the disulfide bridge", "the disulfide bridge is reduced", "disulfide bridge is reduced by", "bridge is reduced by an", "is reduced by an electron", "reduced by an electron donor", "an electron donor the", "electron donor the nadph", "donor the nadph dependent", "the nadph dependent thioredoxin/tr system", "dependent thioredoxin/tr system leading", "thioredoxin/tr system leading to", "system leading to the", "leading to the regeneration of", "to the regeneration of the", "the regeneration of the msr", "regeneration of the msr active", "of the msr active site", "msr active site boschi", "active site boschi muller", "site boschi muller et", "boschi muller et al. 2008", "muller et al. 2008 .

              beta", "et al. 2008 .

              beta linked", "al. 2008 .

              beta linked isoaspartyl", ".

              beta linked isoaspartyl isoasp", "isoaspartyl isoasp peptide", "isoasp peptide bonds can", "peptide bonds can arise spontaneously", "bonds can arise spontaneously via", "can arise spontaneously via succinimide", "arise spontaneously via succinimide linked", "spontaneously via succinimide linked deamidation", "via succinimide linked deamidation of", "succinimide linked deamidation of asparagine", "deamidation of asparagine asn", "asparagine asn or", "asn or dehydration of", "dehydration of aspartate asp", "of aspartate asp .", "aspartate asp . protein", "asp . protein l isoaspartate", "protein l isoaspartate d", "l isoaspartate d aspartate", "d aspartate o methyltransferase", "methyltransferase pcmt1 pimt", "pcmt1 pimt ec 2.1.1.77", "pimt ec 2.1.1.77 transfers", "ec 2.1.1.77 transfers the", "2.1.1.77 transfers the methyl", "transfers the methyl group from", "the methyl group from s", "methyl group from s adenosyl", "group from s adenosyl l", "from s adenosyl l methionine", "adenosyl l methionine adomet", "methionine adomet to", "adomet to the alpha", "to the alpha side chain", "the alpha side chain carboxyl", "alpha side chain carboxyl group", "side chain carboxyl group of", "chain carboxyl group of l", "carboxyl group of l isoaspartyl", "group of l isoaspartyl and", "of l isoaspartyl and d", "l isoaspartyl and d aspartatyl", "isoaspartyl and d aspartatyl amino", "and d aspartatyl amino acids.", "d aspartatyl amino acids. the", "aspartatyl amino acids. the resulting", "amino acids. the resulting methyl", "acids. the resulting methyl ester", "the resulting methyl ester undergoes", "resulting methyl ester undergoes spontaneous", "methyl ester undergoes spontaneous transformation", "ester undergoes spontaneous transformation to", "undergoes spontaneous transformation to l", "spontaneous transformation to l succinimide", "to l succinimide which", "l succinimide which spontaneously", "succinimide which spontaneously hydrolyses", "which spontaneously hydrolyses to generates", "spontaneously hydrolyses to generates l", "hydrolyses to generates l aspartyl", "to generates l aspartyl residues", "generates l aspartyl residues or", "l aspartyl residues or l", "aspartyl residues or l isoaspartyl", "residues or l isoaspartyl residues", "l isoaspartyl residues knorre", "isoaspartyl residues knorre et", "residues knorre et al.", "knorre et al. 2009 .", "et al. 2009 . this", "al. 2009 . this repair", "2009 . this repair process", ". this repair process helps", "this repair process helps to", "repair process helps to maintain", "process helps to maintain overall", "helps to maintain overall protein", "to maintain overall protein integrity." ] }, { "record_id": "GLY_000594_1_1446", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5678771", "r hsa", "hsa 5678771", "r hsa 5678771" ] }, { "record_id": "GLY_000594_1_1446", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abcb4", "abcb4 causes", "causes pfic3", "icp3 and", "and gbd1", "defective abcb4 causes", "abcb4 causes pfic3", "pfic3 icp3", "icp3 and gbd1", "defective abcb4 causes pfic3", "causes pfic3 icp3", "pfic3 icp3 and", "abcb4 causes pfic3 icp3", "causes pfic3 icp3 and", "pfic3 icp3 and gbd1", "multidrug resistance", "resistance protein", "protein 3", "atp binding", "binding cassette", "cassette sub", "sub family", "family b", "b member", "member 4", "abcb4 aka", "aka mdr3", "mediates the", "the atp", "atp dependent", "dependent export", "export of", "of organic", "organic anions", "phospholipids and", "and drugs", "drugs from", "from hepatocytes", "hepatocytes into", "into the", "the canalicular", "canalicular lumen", "lumen in", "in the", "the presence", "presence of", "of bile", "bile salts", "especially the", "the export", "of phospholipids", "phospholipids such", "such as", "as phosphatidylcholine", "pc .", ". biliary", "biliary phospholipids", "phospholipids associate", "associate with", "with bile", "salts and", "and cholesterol", "cholesterol in", "in mixed", "mixed micelles", "thereby reducing", "reducing the", "the detergent", "detergent activity", "activity and", "and cytotoxicity", "cytotoxicity of", "and preventing", "preventing cholesterol", "cholesterol crystallisation.", "crystallisation. thus", "abcb4 plays", "plays a", "a crucial", "crucial role", "role in", "in bile", "bile formation", "formation and", "and lipid", "lipid homeostasis.", "homeostasis. defects", "defects in", "in abcb4", "abcb4 result", "result in", "in a", "a wide", "wide spectrum", "spectrum of", "of cholestasis", "cholestasis phenotypes", "from progressive", "progressive familial", "familial intrahepatic", "intrahepatic cholestasis", "cholestasis 3", "and intrahepatic", "cholestasis of", "of pregnancy", "pregnancy 3", "to gallbladder", "gallbladder disease", "disease 1", "jacquemin et", "et al.", "al. 2001", "davit spraul", "spraul et", "al. 2010", "jacquemin 2012", "2012 .", ". in", "in pfic3", "the biliary", "biliary phospholipid", "phospholipid level", "level is", "is substantially", "substantially decreased", "decreased despite", "despite the", "bile acids.", "acids. cholestasis", "cholestasis may", "may be", "be caused", "caused by", "by the", "the toxicity", "toxicity of", "of detergent", "detergent bile", "salts that", "that are", "are not", "not associated", "associated with", "with phospholipids", "leading to", "to bile", "bile canaliculus", "canaliculus and", "and biliary", "biliary epithelium", "epithelium damage.", "damage. icp3", "icp3 is", "is a", "a reversible", "reversible form", "form of", "cholestasis in", "the third", "third trimester", "trimester of", "pregnancy and", "and quickly", "quickly disappears", "disappears after", "after childbearing.", "childbearing. gbd1", "gbd1 is", "is one", "one of", "of the", "the major", "major digestive", "digestive diseases.", "diseases. gallstones", "gallstones composed", "composed 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"lifetimes but approximately", "but approximately 10", "approximately 10 50%", "10 50% of", "50% of individuals", "of individuals eventually", "individuals eventually develop", "eventually develop symptoms.", "multidrug resistance protein 3", "protein 3 atp", "3 atp binding", "atp binding cassette sub", "binding cassette sub family", "cassette sub family b", "sub family b member", "family b member 4", "member 4 abcb4", "4 abcb4 aka", "aka mdr3 mediates", "mdr3 mediates the", "mediates the atp dependent", "the atp dependent export", "atp dependent export of", "dependent export of organic", "export of organic anions", "organic anions phospholipids", "anions phospholipids and", "phospholipids and drugs from", "and drugs from hepatocytes", "drugs from hepatocytes into", "from hepatocytes into the", "hepatocytes into the canalicular", "into the canalicular lumen", "the canalicular lumen in", "canalicular lumen in the", "lumen in the presence", "in the presence of", "the presence of bile", 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"cholestasis of pregnancy 3", "pregnancy 3 icp3", "mim:614972 to gallbladder", "614972 to gallbladder", "to gallbladder disease 1", "disease 1 gbd1", "mim:600803 jacquemin", "600803 jacquemin", "jacquemin et al. 2001", "al. 2001 davit", "2001 davit spraul", "davit spraul et al.", "spraul et al. 2010", "al. 2010 jacquemin", "2010 jacquemin 2012", "jacquemin 2012 . in", "2012 . in pfic3", "in pfic3 the", "pfic3 the biliary", "the biliary phospholipid level", "biliary phospholipid level is", "phospholipid level is substantially", "level is substantially decreased", "is substantially decreased despite", "substantially decreased despite the", "decreased despite the presence", "despite the presence of", "presence of bile acids.", "of bile acids. cholestasis", "bile acids. cholestasis may", "acids. cholestasis may be", "cholestasis may be caused", "may be caused by", "be caused by the", "caused by the toxicity", "by the toxicity of", "the toxicity of detergent", "toxicity of detergent bile", "of detergent bile salts", "detergent bile salts that", "bile salts that are", "salts that are not", "that are not associated", "are not associated with", "not associated with phospholipids", "with phospholipids leading", "phospholipids leading to", "leading to bile canaliculus", "to bile canaliculus and", "bile canaliculus and biliary", "canaliculus and biliary epithelium", "and biliary epithelium damage.", "biliary epithelium damage. icp3", "epithelium damage. icp3 is", "damage. icp3 is a", "icp3 is a reversible", "is a reversible form", "a reversible form of", "reversible form of cholestasis", "form of cholestasis in", "of cholestasis in the", "cholestasis in the third", "in the third trimester", "the third trimester of", "third trimester of pregnancy", "trimester of pregnancy and", "of pregnancy and quickly", "pregnancy and quickly disappears", "and quickly disappears after", "quickly disappears after childbearing.", "disappears after childbearing. gbd1", "after childbearing. gbd1 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50%", "approximately 10 50% of", "10 50% of individuals", "50% of individuals eventually", "of individuals eventually develop", "individuals eventually develop symptoms.", "resistance protein 3 atp", "protein 3 atp binding", "3 atp binding cassette", "atp binding cassette sub family", "binding cassette sub family b", "cassette sub family b member", "sub family b member 4", "b member 4 abcb4", "member 4 abcb4 aka", "4 abcb4 aka mdr3", "abcb4 aka mdr3 mediates", "aka mdr3 mediates the", "mdr3 mediates the atp", "mediates the atp dependent export", "the atp dependent export of", "atp dependent export of organic", "dependent export of organic anions", "of organic anions phospholipids", "organic anions phospholipids and", "anions phospholipids and drugs", "phospholipids and drugs from hepatocytes", "and drugs from hepatocytes into", "drugs from hepatocytes into the", "from hepatocytes into the canalicular", "hepatocytes into the canalicular lumen", "into the canalicular lumen in", "the 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spectrum of", "a wide spectrum of cholestasis", "wide spectrum of cholestasis phenotypes", "of cholestasis phenotypes from", "cholestasis phenotypes from progressive", "phenotypes from progressive familial", "from progressive familial intrahepatic cholestasis", "progressive familial intrahepatic cholestasis 3", "intrahepatic cholestasis 3 pfic3", "3 pfic3 mim:602347", "pfic3 mim:602347 and", "mim:602347 and intrahepatic cholestasis", "602347 and intrahepatic cholestasis", "and intrahepatic cholestasis of pregnancy", "intrahepatic cholestasis of pregnancy 3", "of pregnancy 3 icp3", "3 icp3 mim:614972", "icp3 mim:614972 to", "mim:614972 to gallbladder disease", "614972 to gallbladder disease", "gallbladder disease 1 gbd1", "1 gbd1 mim:600803", "mim:600803 jacquemin et", "600803 jacquemin et", "et al. 2001 davit", "al. 2001 davit spraul", "2001 davit spraul et", "davit spraul et al. 2010", "et al. 2010 jacquemin", "al. 2010 jacquemin 2012", "2010 jacquemin 2012 .", "jacquemin 2012 . in pfic3", ". in pfic3 the", "in pfic3 the biliary", "pfic3 the biliary phospholipid", "the biliary phospholipid level is", "biliary phospholipid level is substantially", "phospholipid level is substantially decreased", "level is substantially decreased despite", "is substantially decreased despite the", "substantially decreased despite the presence", "decreased despite the presence of", "despite the presence of bile", "the presence of bile acids.", "presence of bile acids. cholestasis", "of bile acids. cholestasis may", "bile acids. cholestasis may be", "acids. cholestasis may be caused", "cholestasis may be caused by", "may be caused by the", "be caused by the toxicity", "caused by the toxicity of", "by the toxicity of detergent", "the toxicity of detergent bile", "toxicity of detergent bile salts", "of detergent bile salts that", "detergent bile salts that are", "bile salts that are not", "salts that are not associated", "that are not associated with", "are not associated with 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"remain asymptomatic throughout their lifetimes", "asymptomatic throughout their lifetimes but", "throughout their lifetimes but approximately", "their lifetimes but approximately 10", "lifetimes but approximately 10 50%", "but approximately 10 50% of", "approximately 10 50% of individuals", "10 50% of individuals eventually", "50% of individuals eventually develop", "of individuals eventually develop symptoms." ] }, { "record_id": "GLY_000594_1_1447", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5684996", "r hsa", "hsa 5684996", "r hsa 5684996" ] }, { "record_id": "GLY_000594_1_1447", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mapk1/mapk3 signaling", "the extracellular", "extracellular signal", "signal regulated", "regulated kinases", "1 and", "and 2", "also known", "known as", "as mapk3", "mapk3 and", "and mapk1", "are phosphorylated", "phosphorylated by", "by the", "the map2ks", 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"phraselist": [ "galactose catabolism", "the main", "main sources", "sources of", "of galactose", "galactose in", "in the", "the human", "human diet", "diet are", "are milk", "milk and", "and milk", "milk products.", "products. the", "the disaccharide", "disaccharide lactose", "lactose from", "from these", "these sources", "sources is", "is hydrolyzed", "hydrolyzed in", "the intestine", "intestine to", "to its", "its constituent", "constituent monosaccharides", "glucose and", "and galactose.", "galactose. galactose", "galactose is", "is metabolized", "metabolized primarily", "primarily in", "the liver", "liver in", "in a", "a sequence", "sequence of", "of three", "three reactions", "reactions that", "that yield", "yield one", "one molecule", "molecule of", "of glucose", "glucose 1", "1 phosphate", "phosphate per", "per molecule", "of galactose.", "galactose. first", "it is", "is phosphorylated", "phosphorylated to", "to yield", "yield galactose", "galactose 1", "1 phosphate.", "phosphate. then", "phosphate and", "and udp", "udp glucose", "glucose react", "react to", "to form", "form udp", "udp galactose", "galactose and", "and glucose", "galactose undergoes", "undergoes epimerization", "epimerization to", "udp glucose.", "glucose. in", "a reaction", "reaction shared", "shared with", "with other", "other pathways", "phosphate can", "can be", "be converted", "converted into", "into glucose", "glucose 6", "6 phosphate", "holton et", "et al.", "al. 2001", "elsas and", "and lai", "lai 2001", "2001 .", "the main sources", "main sources of", "sources of galactose", "of galactose in", "galactose in the", "in the human", "the human diet", "human diet are", "diet are milk", "are milk and", "milk and milk", "and milk products.", "milk products. the", "products. the disaccharide", "the disaccharide lactose", "disaccharide lactose from", "lactose from these", "from these sources", "these sources is", "sources is hydrolyzed", "is hydrolyzed in", "hydrolyzed in the", "in the intestine", "the intestine to", "intestine to its", "to its constituent", "its constituent monosaccharides", "monosaccharides glucose", "glucose and galactose.", "and galactose. galactose", "galactose. galactose is", "galactose is metabolized", "is metabolized primarily", "metabolized primarily in", "primarily in the", "in the liver", "the liver in", "liver in a", "in a sequence", "a sequence of", "sequence of three", "of three reactions", "three reactions that", "reactions that yield", "that yield one", "yield one molecule", "one molecule of", "molecule of glucose", "of glucose 1", "glucose 1 phosphate", "1 phosphate per", "phosphate per molecule", "per molecule of", "molecule of galactose.", "of galactose. first", "first it", "it is phosphorylated", "is phosphorylated to", "phosphorylated to yield", "to yield galactose", "yield galactose 1", "galactose 1 phosphate.", "1 phosphate. then", "then galactose", "galactose 1 phosphate", "1 phosphate and", "phosphate and udp", "and udp glucose", "udp glucose react", "glucose react to", "react to form", "to form udp", "form udp galactose", "udp galactose and", "galactose and glucose", "and glucose 1", "and udp galactose", "udp galactose undergoes", "galactose undergoes epimerization", "undergoes epimerization to", "epimerization to form", "form udp glucose.", "udp glucose. in", "glucose. in a", "in a reaction", "a reaction shared", "reaction shared with", "shared with other", "with other pathways", "pathways glucose", "1 phosphate can", "phosphate can be", "can be converted", "be converted into", "converted into glucose", "into glucose 6", "glucose 6 phosphate", "phosphate holton", "holton et al.", "et al. 2001", "2001 elsas", "elsas and lai", "and lai 2001", "lai 2001 .", "the main sources of", "main sources of galactose", "sources of galactose in", "of galactose in the", "galactose in the human", "in the human diet", "the human diet are", "human diet are milk", "diet are milk and", "are milk and milk", "milk and milk products.", "and milk products. the", "milk products. the disaccharide", "products. the disaccharide lactose", "the disaccharide lactose from", "disaccharide lactose from these", "lactose from these sources", "from these sources is", "these sources is hydrolyzed", "sources is hydrolyzed in", "is hydrolyzed in the", "hydrolyzed in the intestine", "in the intestine to", "the intestine to its", "intestine to its constituent", "to its constituent monosaccharides", "constituent monosaccharides glucose", "monosaccharides glucose and", "glucose and galactose. galactose", "and galactose. galactose is", "galactose. galactose is metabolized", "galactose is metabolized primarily", "is metabolized primarily in", "metabolized primarily in the", "primarily in the liver", "in the liver in", "the liver in a", "liver in a sequence", "in a sequence of", "a sequence of three", "sequence of three reactions", "of three reactions that", "three reactions that yield", "reactions that yield one", "that yield one molecule", "yield one molecule of", "one molecule of glucose", "molecule of glucose 1", "of glucose 1 phosphate", "glucose 1 phosphate per", "1 phosphate per molecule", "phosphate per molecule of", "per molecule of galactose.", "molecule of galactose. first", "galactose. first it", "first it is", "it is phosphorylated to", "is phosphorylated to yield", "phosphorylated to yield galactose", "to yield galactose 1", "yield galactose 1 phosphate.", "galactose 1 phosphate. then", "phosphate. then galactose", "then galactose 1", "galactose 1 phosphate and", "1 phosphate and udp", "phosphate and udp glucose", "and udp glucose react", "udp glucose react to", "glucose react to form", "react to form udp", "to form udp galactose", "form udp galactose and", "udp galactose and glucose", "galactose and glucose 1", "and glucose 1 phosphate", "and udp galactose undergoes", "udp galactose undergoes epimerization", "galactose undergoes epimerization to", "undergoes epimerization to form", "epimerization to form udp", "to form udp glucose.", "form udp glucose. in", "udp glucose. in a", "glucose. in a reaction", "in a reaction shared", "a reaction shared with", "reaction shared with other", "shared with other pathways", "other pathways glucose", "pathways glucose 1", "glucose 1 phosphate can", "1 phosphate can be", "phosphate can be converted", "can be converted into", "be converted into glucose", "converted into glucose 6", "into glucose 6 phosphate", "6 phosphate holton", "phosphate holton et", "holton et al. 2001", "al. 2001 elsas", "2001 elsas and", "elsas and lai 2001", "and lai 2001 .", "the main sources of galactose", "main sources of galactose in", "sources of galactose in the", "of galactose in the human", "galactose in the human diet", "in the human diet are", "the human diet are milk", "human diet are milk and", "diet are milk and milk", "are milk and milk products.", "milk and milk products. the", "and milk products. the disaccharide", "milk products. the disaccharide lactose", "products. the disaccharide lactose from", "the disaccharide lactose from these", "disaccharide lactose from these sources", "lactose from these sources is", "from these sources is hydrolyzed", "these sources is hydrolyzed in", "sources is hydrolyzed in the", "is hydrolyzed in the intestine", "hydrolyzed in the intestine to", "in the intestine to its", "the intestine to its constituent", "intestine to its constituent monosaccharides", "its constituent monosaccharides glucose", "constituent monosaccharides glucose and", "monosaccharides glucose and galactose.", "glucose and galactose. galactose is", "and galactose. galactose is metabolized", "galactose. galactose is metabolized primarily", "galactose is metabolized primarily in", "is metabolized primarily in the", "metabolized primarily in the liver", "primarily in the liver in", "in the liver in a", "the liver in a sequence", "liver in a sequence of", "in a sequence of three", "a sequence of three reactions", "sequence of three reactions that", "of three reactions that yield", "three reactions that yield one", "reactions that yield one molecule", "that yield one molecule of", "yield one molecule of glucose", "one molecule of glucose 1", "molecule of glucose 1 phosphate", "of glucose 1 phosphate per", "glucose 1 phosphate per molecule", "1 phosphate per molecule of", "phosphate per molecule of galactose.", "per molecule of galactose. first", "of galactose. first it", "galactose. first it is", "first it is phosphorylated", "it is phosphorylated to yield", "is phosphorylated to yield galactose", "phosphorylated to yield galactose 1", "to yield galactose 1 phosphate.", "yield galactose 1 phosphate. then", "1 phosphate. then galactose", "phosphate. then galactose 1", "then galactose 1 phosphate", "galactose 1 phosphate and udp", "1 phosphate and udp glucose", "phosphate and udp glucose react", "and udp glucose react to", "udp glucose react to form", "glucose react to form udp", "react to form udp galactose", "to form udp galactose and", "form udp galactose and glucose", "udp galactose and glucose 1", "galactose and glucose 1 phosphate", "glucose 1 phosphate and", "phosphate and udp galactose", "and udp galactose undergoes epimerization", "udp galactose undergoes epimerization to", "galactose undergoes epimerization to form", "undergoes epimerization to form udp", "epimerization to form udp glucose.", "to form udp glucose. in", "form udp glucose. in a", "udp glucose. in a reaction", "glucose. in a reaction shared", "in a reaction shared with", "a reaction shared with other", "reaction shared with other pathways", "with other pathways glucose", "other pathways glucose 1", "pathways glucose 1 phosphate", "glucose 1 phosphate can be", "1 phosphate can be converted", "phosphate can be converted into", "can be converted into glucose", "be converted into glucose 6", "converted into glucose 6 phosphate", "glucose 6 phosphate holton", "6 phosphate holton et", "phosphate holton et al.", "et al. 2001 elsas", "al. 2001 elsas and", "2001 elsas and lai", "elsas and lai 2001 ." ] }, { "record_id": "GLY_000594_1_1468", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71032", "r hsa", "hsa 71032", "r hsa 71032" ] }, { "record_id": "GLY_000594_1_1468", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "propionyl coa", "coa catabolism", "propionyl coa catabolism", "coa is", "is a", "a product", "product of", "of the", "the catabolism", "catabolism of", "the amino", "amino acids", "and threonine", "and of", "the beta", "beta oxidation", "oxidation of", "of fatty", "fatty acids", "acids with", "with odd", "odd numbers", "numbers of", "of carbon", "carbon atoms.", "the three", "three reactions", "reactions of", "of this", "this pathway", "pathway convert", "convert propionyl", "coa to", "to succinyl", "succinyl coa", "an intermediate", "intermediate of", "the citric", "citric acid", "acid cycle.", "through these", "these reactions", "carbon atoms", "atoms from", "from these", "these sources", "sources can", "can be", "be fully", "fully oxidized", "oxidized to", "to produce", "produce energy", "or can", "be directed", "directed to", "to gluconeogenesis.", "of propionyl", "catabolism take", "take place", "place in", "in the", "the mitochondrial", "mitochondrial matrix.", "propionyl coa is", "coa is a", "is a product", "a product of", "product of the", "of the catabolism", "the catabolism of", "catabolism of the", "of the amino", "the amino acids", "acids leucine", "leucine methionine", "methionine and", "threonine and", "and of the", "of the beta", "the beta oxidation", "beta oxidation of", "oxidation of fatty", "of fatty acids", "fatty acids with", "acids with odd", "with odd numbers", "odd numbers of", "numbers of carbon", "of carbon atoms.", "atoms. the", "the three reactions", "three reactions of", "reactions of this", "of this pathway", "this pathway convert", "pathway convert propionyl", "convert propionyl coa", "propionyl coa to", "coa to succinyl", "to succinyl coa", "coa an", "an intermediate of", "intermediate of the", "of the citric", "the citric acid", "citric acid cycle.", "cycle. through", "through these reactions", "reactions carbon", "carbon atoms from", "atoms from these", "from these sources", "these sources can", "sources can be", "can be fully", "be fully oxidized", "fully oxidized to", "oxidized to produce", "to produce energy", "energy or", "or can be", "can be directed", "be directed to", "directed to gluconeogenesis.", "gluconeogenesis. the", "reactions of propionyl", "of propionyl coa", "coa catabolism take", "catabolism take place", "take place in", "place in the", "in the mitochondrial", "the mitochondrial matrix.", "propionyl coa is a", "coa is a product", "is a product of", "a product of the", "product of the catabolism", "of the catabolism of", "the catabolism of the", "catabolism of the amino", "of the amino acids", "amino acids leucine", "methionine and threonine", "and threonine and", "threonine and of", "and of the beta", "of the beta oxidation", "the beta oxidation of", "beta oxidation of fatty", "oxidation of fatty acids", "of fatty acids with", "fatty acids with odd", "acids with odd numbers", "with odd numbers of", "odd numbers of carbon", "numbers of carbon atoms.", "carbon atoms. the", "atoms. the three", "the three reactions of", "three reactions of this", "reactions of this pathway", "of this pathway convert", "this pathway convert propionyl", "pathway convert propionyl coa", "convert propionyl coa to", "propionyl coa to succinyl", "coa to succinyl coa", "succinyl coa an", "coa an intermediate", "an intermediate of the", "intermediate of the citric", "of the citric acid", "the citric acid cycle.", "acid cycle. through", "cycle. through these", "these reactions carbon", "reactions carbon atoms", "carbon atoms from these", "atoms from these sources", "from these sources can", "these sources can be", "sources can be fully", "can be fully oxidized", "be fully oxidized to", "fully oxidized to produce", "oxidized to produce energy", "produce energy or", "energy or can", "or can be directed", "can be directed to", "be directed to gluconeogenesis.", "to gluconeogenesis. the", "gluconeogenesis. the three", "three reactions of propionyl", "reactions of propionyl coa", "of propionyl coa catabolism", "propionyl coa catabolism take", "coa catabolism take place", "catabolism take place in", "take place in the", "place in the mitochondrial", "in the mitochondrial matrix.", "propionyl coa is a product", "coa is a product of", "is a product of the", "a product of the catabolism", "product of the catabolism of", "of the catabolism of the", "the catabolism of the amino", "catabolism of the amino acids", "the amino acids leucine", "acids leucine methionine", "leucine methionine and", "and threonine and of", "threonine and of the", "and of the beta oxidation", "of the beta oxidation of", "the beta oxidation of fatty", "beta oxidation of fatty acids", "oxidation of fatty acids with", "of fatty acids with odd", "fatty acids with odd numbers", "acids with odd numbers of", "with odd numbers of carbon", "odd numbers of carbon atoms.", "of carbon atoms. the", "carbon atoms. the three", "atoms. the three reactions", "the three reactions of this", "three reactions of this pathway", "reactions of this pathway convert", "of this pathway convert propionyl", "this pathway convert propionyl coa", "pathway convert propionyl coa to", "convert propionyl coa to succinyl", "propionyl coa to succinyl coa", "to succinyl coa an", "succinyl coa an intermediate", "coa an intermediate of", "an intermediate of the citric", "intermediate of the citric acid", "of the citric acid cycle.", "citric acid cycle. through", "acid cycle. through these", "cycle. through these reactions", "through these reactions carbon", "these reactions carbon atoms", "reactions carbon atoms from", "carbon atoms from these sources", "atoms from these sources can", "from these sources can be", "these sources can be fully", "sources can be fully oxidized", "can be fully oxidized to", "be fully oxidized to produce", "fully oxidized to produce energy", "to produce energy or", "produce energy or can", "energy or can be", "or can be directed to", "can be directed to gluconeogenesis.", "directed to gluconeogenesis. the", "to gluconeogenesis. the three", "gluconeogenesis. the three reactions", "the three reactions of propionyl", "three reactions of propionyl coa", "reactions of propionyl coa catabolism", "of propionyl coa catabolism take", "propionyl coa catabolism take place", "coa catabolism take place in", "catabolism take place in the", "take place in the mitochondrial", "place in the mitochondrial matrix." ] }, { "record_id": "GLY_000594_1_1469", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "71288", "r hsa", "hsa 71288", "r hsa 71288" ] }, { "record_id": "GLY_000594_1_1469", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "creatine metabolism", "in humans", "creatine is", "is synthesized", "synthesized primarily", "primarily in", "in the", "the liver", "liver and", "and kidney", "from glycine", "and s", "s adenosylmethionine", "in a", "a sequence", "sequence of", "of two", "two reactions.", "reactions. from", "from the", "is exported", "exported to", "to tissues", "tissues such", "such as", "as skeletal", "skeletal muscle", "muscle and", "and brain", "where it", "it undergoes", "undergoes phosphorylation", "phosphorylation and", "and serves", "serves as", "as a", "a short", "short term", "term energy", "energy store.", "store. the", "the mechanism", "mechanism by", "by which", "which creatine", "creatine leaves", "leaves producer", "producer tissues", "tissues is", "is unclear", "but its", "its uptake", "uptake by", "by consumer", "consumer tissues", "is mediated", "mediated by", "by the", "the slc6a8", "slc6a8 transporter.

              once", "transporter.

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              once", "slc6a8 transporter.

              once formed", "formed phosphocreatine", "phosphocreatine undergoes a", "undergoes a slow", "a slow spontaneous", "slow spontaneous reaction", "spontaneous reaction to", "reaction to form", "to form creatinine", "creatinine which", "which is excreted", "is excreted from", "excreted from the", "from the body.", "in humans creatine", "humans creatine is", "creatine is synthesized primarily", "is synthesized primarily in", "synthesized primarily in the", "primarily in the liver", "in the liver and", "the liver and kidney", "and kidney from", "kidney from glycine", "from glycine arginine", "arginine and s", "s adenosylmethionine in", "adenosylmethionine in a", "in a sequence of", "a sequence of two", "sequence of two reactions.", "of two reactions. from", "two reactions. from the", "reactions. from the liver", "the liver creatine", "liver creatine is", "creatine is exported to", "is exported to tissues", "exported to tissues such", "to tissues such as", "tissues such as skeletal", "such as skeletal muscle", "as skeletal muscle and", "skeletal muscle and brain", "and brain where", "brain where it", "where it undergoes phosphorylation", "it undergoes phosphorylation and", "undergoes phosphorylation and serves", "phosphorylation and serves as", "and serves as a", "serves as a short", "as a short term", "a short term energy", "short term energy store.", "term energy store. the", "energy store. the mechanism", "store. the mechanism by", "the mechanism by which", "mechanism by which creatine", "by which creatine leaves", "which creatine leaves producer", "creatine leaves producer tissues", "leaves producer tissues is", "producer tissues is unclear", "is unclear but", "unclear but its", "but its uptake by", "its uptake by consumer", "uptake by consumer tissues", "by consumer tissues is", "consumer tissues is mediated", "tissues is mediated by", "is mediated by the", "mediated by the slc6a8", "by the slc6a8 transporter.

              once", "the slc6a8 transporter.

              once formed", "transporter.

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              once", "by the slc6a8 transporter.

              once formed", "slc6a8 transporter.

              once formed phosphocreatine", "transporter.

              once formed phosphocreatine undergoes", "formed phosphocreatine undergoes a", "phosphocreatine undergoes a slow spontaneous", "undergoes a slow spontaneous reaction", "a slow spontaneous reaction to", "slow spontaneous reaction to form", "spontaneous reaction to form creatinine", "to form creatinine which", "form creatinine which is", "creatinine which is excreted", "which is excreted from the", "is excreted from the body." ] }, { "record_id": "GLY_000594_1_1470", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72731", "r hsa", "hsa 72731", "r hsa 72731" ] }, { "record_id": "GLY_000594_1_1470", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "recycling of", "of eif2:gdp", "recycling of eif2:gdp", "the active", "active eif2:gtp", "eif2:gtp complex", "complex may", "may be", "be formed", "formed by", "by direct", "direct binding", "binding of", "of gtp", "gtp to", "to free", "free eif2", "eif2 or", "or by", "by gdp", "gdp gtp", "gtp exchange", "exchange on", "on the", "the eif2:gdp:eif2b", "eif2:gdp:eif2b complex.", "complex. the", "the eif2:gdp", "eif2:gdp complex", "complex binds", "binds eif2b", "eif2b forming", "forming an", "an eif2:gdp:eif2b", "eif2:gdp:eif2b intermediate", "intermediate complex.", "complex. eif2b", "eif2b is", "is a", "a guanine", "guanine nucleotide", "nucleotide releasing", "releasing factor", "factor required", "required to", "to cause", "cause gdp", "gdp release", "release so", "so that", "that a", "a new", "new gtp", "gtp molecule", "molecule can", "can bind", "bind and", "and activate", "activate eif2.", "eif2. phosphorylated", "phosphorylated eif2:gdp", "eif2:gdp sequesters", "sequesters all", "all eif2b", "eif2b as", "as an", "an inactive", "inactive complex", "and thus", "reuse of", "of eif2", "eif2 is", "is inhibited", "inhibited as", "as a", "a consequence", "consequence of", "of the", "the tight", "tight bond", "bond it", "it forms", "forms with", "with eif2b", "which prevents", "prevents nucleotide", "nucleotide exchange.", "exchange. therefore", "in the", "the absence", "absence of", "of free", "free eif2b", "excess eif2", "eif2 remains", "remains in", "in its", "its inactive", "inactive gdp", "gdp bound", "bound form", "form and", "and protein", "protein synthesis", "synthesis slows", "slows dramatically.", "the active eif2:gtp", "active eif2:gtp complex", "eif2:gtp complex may", "complex may be", "may be formed", "be formed by", "formed by direct", "by direct binding", "direct binding of", "binding of gtp", "of gtp to", "gtp to free", "to free eif2", "free eif2 or", "eif2 or by", "or by gdp", "by gdp gtp", "gdp gtp exchange", "gtp exchange on", "exchange on the", "on the eif2:gdp:eif2b", "the eif2:gdp:eif2b complex.", "eif2:gdp:eif2b complex. the", "complex. the eif2:gdp", "the eif2:gdp complex", "eif2:gdp complex binds", "complex binds eif2b", "binds eif2b forming", "eif2b forming an", "forming an eif2:gdp:eif2b", "an eif2:gdp:eif2b intermediate", "eif2:gdp:eif2b intermediate complex.", "intermediate complex. eif2b", "complex. eif2b is", "eif2b is a", "is a guanine", "a guanine nucleotide", "guanine nucleotide releasing", "nucleotide releasing factor", "releasing factor required", "factor required to", "required to cause", "to cause gdp", "cause gdp release", "gdp release so", "release so that", "so that a", "that a new", "a new gtp", "new gtp molecule", "gtp molecule can", "molecule can bind", "can bind and", "bind and activate", "and activate eif2.", "activate eif2. phosphorylated", "eif2. phosphorylated eif2:gdp", "phosphorylated eif2:gdp sequesters", "eif2:gdp sequesters all", "sequesters all eif2b", "all eif2b as", "eif2b as an", "as an inactive", "an inactive complex", "complex and", "thus reuse", "reuse of eif2", "of eif2 is", "eif2 is inhibited", "is inhibited as", "inhibited as a", "as a consequence", "a consequence of", "consequence of the", "of the tight", "the tight bond", "tight bond it", "bond it forms", "it forms with", "forms with eif2b", "eif2b which", "which prevents nucleotide", "prevents nucleotide exchange.", "nucleotide exchange. therefore", "therefore in", "in the absence", "the absence of", "absence of free", "of free eif2b", "eif2b excess", "excess eif2 remains", "eif2 remains in", "remains in its", "in its inactive", "its inactive gdp", "inactive gdp bound", "gdp bound form", "bound form and", "form and protein", "and protein synthesis", "protein synthesis slows", "synthesis slows dramatically.", "the active eif2:gtp complex", "active eif2:gtp complex may", "eif2:gtp complex may be", "complex may be formed", "may be formed by", "be formed by direct", "formed by direct binding", "by direct binding of", "direct binding of gtp", "binding of gtp to", "of gtp to free", "gtp to free eif2", "to free eif2 or", "free eif2 or by", "eif2 or by gdp", "or by gdp gtp", "by gdp gtp exchange", "gdp gtp exchange on", "gtp exchange on the", "exchange on the eif2:gdp:eif2b", "on the eif2:gdp:eif2b complex.", "the eif2:gdp:eif2b complex. the", "eif2:gdp:eif2b complex. the eif2:gdp", "complex. the eif2:gdp complex", "the eif2:gdp complex binds", "eif2:gdp complex binds eif2b", "complex binds eif2b forming", "binds eif2b forming an", "eif2b forming an eif2:gdp:eif2b", "forming an eif2:gdp:eif2b intermediate", "an eif2:gdp:eif2b intermediate complex.", "eif2:gdp:eif2b intermediate complex. eif2b", "intermediate complex. eif2b is", "complex. eif2b is a", "eif2b is a guanine", "is a guanine nucleotide", "a guanine nucleotide releasing", "guanine nucleotide releasing factor", "nucleotide releasing factor required", "releasing factor required to", "factor required to cause", "required to cause gdp", "to cause gdp release", "cause gdp release so", "gdp release so that", "release so that a", "so that a new", "that a new gtp", "a new gtp molecule", "new gtp molecule can", "gtp molecule can bind", "molecule can bind and", "can bind and activate", "bind and activate eif2.", "and activate eif2. phosphorylated", "activate eif2. phosphorylated eif2:gdp", "eif2. phosphorylated eif2:gdp sequesters", "phosphorylated eif2:gdp sequesters all", "eif2:gdp sequesters all eif2b", "sequesters all eif2b as", "all eif2b as an", "eif2b as an inactive", "as an inactive complex", "inactive complex and", "complex and thus", "and thus reuse", "thus reuse of", "reuse of eif2 is", "of eif2 is inhibited", "eif2 is inhibited as", "is inhibited as a", "inhibited as a consequence", "as a consequence of", "a consequence of the", "consequence of the tight", "of the tight bond", "the tight bond it", "tight bond it forms", "bond it forms with", "it forms with eif2b", "with eif2b which", "eif2b which prevents", "which prevents nucleotide exchange.", "prevents nucleotide exchange. therefore", "exchange. therefore in", "therefore in the", "in the absence of", "the absence of free", "absence of free eif2b", "free eif2b excess", "eif2b excess eif2", "excess eif2 remains in", "eif2 remains in its", "remains in its inactive", "in its inactive gdp", "its inactive gdp bound", "inactive gdp bound form", "gdp bound form and", "bound form and protein", "form and protein synthesis", "and protein synthesis slows", "protein synthesis slows dramatically.", "the active eif2:gtp complex may", "active eif2:gtp complex may be", "eif2:gtp complex may be formed", "complex may be formed by", "may be formed by direct", "be formed by direct binding", "formed by direct binding of", "by direct binding of gtp", "direct binding of gtp to", "binding of gtp to free", "of gtp to free eif2", "gtp to free eif2 or", "to free eif2 or by", "free eif2 or by gdp", "eif2 or by gdp gtp", "or by gdp gtp exchange", "by gdp gtp exchange on", "gdp gtp exchange on the", "gtp exchange on the eif2:gdp:eif2b", "exchange on the eif2:gdp:eif2b complex.", "on the eif2:gdp:eif2b complex. the", "the eif2:gdp:eif2b complex. the eif2:gdp", "eif2:gdp:eif2b complex. the eif2:gdp complex", "complex. the eif2:gdp complex binds", "the eif2:gdp complex binds eif2b", "eif2:gdp complex binds eif2b forming", "complex binds eif2b forming an", "binds eif2b forming an eif2:gdp:eif2b", "eif2b forming an eif2:gdp:eif2b intermediate", "forming an eif2:gdp:eif2b intermediate complex.", "an eif2:gdp:eif2b intermediate complex. eif2b", "eif2:gdp:eif2b intermediate complex. eif2b is", "intermediate complex. eif2b is a", "complex. eif2b is a guanine", "eif2b is a guanine nucleotide", "is a guanine nucleotide releasing", "a guanine nucleotide releasing factor", "guanine nucleotide releasing factor required", "nucleotide releasing factor required to", "releasing factor required to cause", "factor required to cause gdp", "required to cause gdp release", "to cause gdp release so", "cause gdp release so that", "gdp release so that a", "release so that a new", "so that a new gtp", "that a new gtp molecule", "a new gtp molecule can", "new gtp molecule can bind", "gtp molecule can bind and", "molecule can bind and activate", "can bind and activate eif2.", "bind and activate eif2. phosphorylated", "and activate eif2. phosphorylated eif2:gdp", "activate eif2. phosphorylated eif2:gdp sequesters", "eif2. phosphorylated eif2:gdp sequesters all", "phosphorylated eif2:gdp sequesters all eif2b", "eif2:gdp sequesters all eif2b as", "sequesters all eif2b as an", "all eif2b as an inactive", "eif2b as an inactive complex", "an inactive complex and", "inactive complex and thus", "and thus reuse of", "thus reuse of eif2", "reuse of eif2 is inhibited", "of eif2 is inhibited as", "eif2 is inhibited as a", "is inhibited as a consequence", "inhibited as a consequence of", "as a consequence of the", "a consequence of the tight", "consequence of the tight bond", "of the tight bond it", "the tight bond it forms", "tight bond it forms with", "bond it forms with eif2b", "forms with eif2b which", "with eif2b which prevents", "eif2b which prevents nucleotide", "which prevents nucleotide exchange. therefore", "nucleotide exchange. therefore in", "exchange. therefore in the", "therefore in the absence", "in the absence of free", "the absence of free eif2b", "of free eif2b excess", "free eif2b excess eif2", "eif2b excess eif2 remains", "excess eif2 remains in its", "eif2 remains in its inactive", "remains in its inactive gdp", "in its inactive gdp bound", "its inactive gdp bound form", "inactive gdp bound form and", "gdp bound form and protein", "bound form and protein synthesis", "form and protein synthesis slows", "and protein synthesis slows dramatically." ] }, { "record_id": "GLY_000594_1_1471", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72764", "r hsa", "hsa 72764", "r hsa 72764" ] }, { "record_id": "GLY_000594_1_1471", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "eukaryotic translation", "translation termination", "eukaryotic translation termination", "the arrival", 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molecule", "molecule to", "to begin", "begin a", "a new", "new round", "round of", "of protein", "protein synthesis.", "synthesis. it", "it should", "should be", "be noted", "noted that", "that at", "at present", "there is", "is no", "no factor", "factor identified", "identified in", "eukaryotes that", "that would", "would be", "be the", "the functional", "functional equivalent", "equivalent of", "the bacterial", "bacterial ribosome", "ribosome release", "or recycling", "that catalyzes", "catalyzes dissociation", "dissociation of", "ribosome from", "from the", "mrna following", "following release", "release of", "the polypeptide", "the arrival of", "arrival of any", "of any of", "any of the", "of the three", "the three stop", "three stop codons", "codons uaa", "uaa uag", "uag and uga", "uga into", "into the ribosomal", "the ribosomal a", "ribosomal a site", "a site triggers", "site triggers the", "triggers the binding", "the binding of", "binding of a", "of a release", "a release 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can reassemble", "can reassemble on", "reassemble on another", "on another molecule", "another molecule to", "molecule to begin", "to begin a", "begin a new", "a new round", "new round of", "round of protein", "of protein synthesis.", "protein synthesis. it", "synthesis. it should", "it should be", "should be noted", "be noted that", "noted that at", "that at present", "present there", "there is no", "is no factor", "no factor identified", "factor identified in", "identified in eukaryotes", "in eukaryotes that", "eukaryotes that would", "that would be", "would be the", "be the functional", "the functional equivalent", "functional equivalent of", "equivalent of the", "of the bacterial", "the bacterial ribosome", "bacterial ribosome release", "release or", "recycling factor", "factor rrf", "rrf that", "that catalyzes dissociation", "catalyzes dissociation of", "dissociation of the", "of the ribosome", "the ribosome from", "ribosome from the", "from the mrna", "the mrna following", "mrna 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protein", "round of protein synthesis.", "of protein synthesis. it", "protein synthesis. it should", "synthesis. it should be", "it should be noted", "should be noted that", "be noted that at", "noted that at present", "at present there", "present there is", "there is no factor", "is no factor identified", "no factor identified in", "factor identified in eukaryotes", "identified in eukaryotes that", "in eukaryotes that would", "eukaryotes that would be", "that would be the", "would be the functional", "be the functional equivalent", "the functional equivalent of", "functional equivalent of the", "equivalent of the bacterial", "of the bacterial ribosome", "the bacterial ribosome release", "ribosome release or", "release or recycling", "or recycling factor", "rrf that catalyzes", "that catalyzes dissociation of", "catalyzes dissociation of the", "dissociation of the ribosome", "of the ribosome from", "the ribosome from the", "ribosome from the mrna", "from the mrna following", "the mrna following release", "mrna following release of", "following release of the", "release of the polypeptide", "the arrival of any of", "arrival of any of the", "of any of the three", "any of the three stop", "of the three stop codons", "three stop codons uaa", "codons uaa uag", "uaa uag and uga", "uag and uga into", "and uga into the", "uga into the ribosomal", "into the ribosomal a site", "the ribosomal a site triggers", "ribosomal a site triggers the", "a site triggers the binding", "site triggers the binding of", "triggers the binding of a", "the binding of a release", "binding of a release factor", "a release factor rf", "factor rf to", "rf to the ribosome", "to the ribosome and subsequent", "the ribosome and subsequent polypeptide", "ribosome and subsequent polypeptide chain", "and subsequent polypeptide chain release.", "subsequent polypeptide chain release. in", "polypeptide chain release. in eukaryotes", "release. in eukaryotes the", "in eukaryotes the rf", "eukaryotes the rf is", "the rf is composed of", "rf is composed of two", "is composed of two proteins", "of two proteins erf1", "two proteins erf1 and", "proteins erf1 and erf3.", "erf1 and erf3. erf1 is", "and erf3. erf1 is responsible", "erf3. erf1 is responsible for", "erf1 is responsible for the", "is responsible for the hydrolysis", "responsible for the hydrolysis of", "for the hydrolysis of the", "the hydrolysis of the peptidyl", "hydrolysis of the peptidyl trna", "the peptidyl trna while", "peptidyl trna while erf3", "trna while erf3 provides", "while erf3 provides a gtp", "erf3 provides a gtp dependent", "provides a gtp dependent function.", "a gtp dependent function. the", "gtp dependent function. the ribosome", "dependent function. the ribosome releases", "function. the ribosome releases the", "the ribosome releases the mrna", "ribosome releases the mrna and", "releases the mrna and dissociates", "the mrna and dissociates into", "mrna and dissociates into its", "and dissociates into its two", "dissociates into its two complex", "into its two complex subunits", "two complex subunits which", "complex subunits which can", "subunits which can reassemble", "which can reassemble on another", "can reassemble on another molecule", "reassemble on another molecule to", "on another molecule to begin", "another molecule to begin a", "molecule to begin a new", "to begin a new round", "begin a new round of", "a new round of protein", "new round of protein synthesis.", "round of protein synthesis. it", "of protein synthesis. it should", "protein synthesis. it should be", "synthesis. it should be noted", "it should be noted that", "should be noted that at", "be noted that at present", "that at present there", "at present there is", "present there is no", "there is no factor identified", "is no factor identified in", "no factor identified in eukaryotes", "factor identified in eukaryotes that", "identified in eukaryotes that would", "in eukaryotes that would be", "eukaryotes that would be the", "that would be the functional", "would be the functional equivalent", "be the functional equivalent of", "the functional equivalent of the", "functional equivalent of the bacterial", "equivalent of the bacterial ribosome", "of the bacterial ribosome release", "bacterial ribosome release or", "ribosome release or recycling", "recycling factor rrf", "factor rrf that", "rrf that catalyzes dissociation", "that catalyzes dissociation of the", "catalyzes dissociation of the ribosome", "dissociation of the ribosome from", "of the ribosome from the", "the ribosome from the mrna", "ribosome from the mrna following", "from the mrna following release", "the mrna following release of", "mrna following release of the", "following release of the polypeptide" ] }, { "record_id": "GLY_000594_1_1472", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "73843", "r hsa", "hsa 73843", "r hsa 73843" ] }, { "record_id": "GLY_000594_1_1472", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "5 phosphoribose", "phosphoribose 1", "1 diphosphate", "diphosphate biosynthesis", "5 phosphoribose 1", "phosphoribose 1 diphosphate", "1 diphosphate biosynthesis", "5 phosphoribose 1 diphosphate", "phosphoribose 1 diphosphate biosynthesis", "5 phosphoribose 1 diphosphate biosynthesis", "5 phospho", "phospho alpha", "alpha d", "d ribose", "ribose 1", "is a", "a key", "key intermediate", "intermediate in", "in both", "both the", "the de", "de novo", "novo and", "and salvage", "salvage pathways", "pathways of", "of purine", "purine and", "and pyrimidine", "pyrimidine synthesis.", "prpp and", "and the", "the enzymatic", "enzymatic activity", "activity responsible", "responsible for", "for its", "its synthesis", "synthesis were", "were first", "first described", "described by", "by kornberg", "kornberg et", "et al.", "1955 .", ". the", "the enzyme", "phosphoribosyl pyrophosphate", "pyrophosphate synthetase", "synthetase 1", "has been", "been purified", "purified from", "from human", "human erythrocytes", "erythrocytes and", "and characterized", "characterized biochemically.", "biochemically. the", "the purified", "purified enzyme", "enzyme readily", "readily forms", "forms multimers", "its smallest", "smallest active", "active form", "form appears", "appears to", "to be", "be a", "a dimer", "dimer and", "and for", "for simplicity", "simplicity it", "it is", "is annotated", "annotated as", "as a", "dimer here.", "here. it", "it specifically", "specifically catalyzes", "catalyzes the", "the transfer", "transfer of", "of pyrophosphate", "pyrophosphate from", "from atp", "atp or", "or datp", "datp to", "to d", "ribose 5", "5 phosphate", "and has", "has an", "an absolute", "absolute requirement", "requirement for", "for mg++", "mg++ and", "and orthophosphate", "fox and", "and kelley", "kelley 1971", "roth et", "al. 1974", "1974 .", "the significance", "significance of", "of the", "the reaction", "reaction with", "with datp", "datp in", "in vivo", "vivo is", "is unclear", "as the", "the concentration", "concentration of", "of cytosolic", "cytosolic datp", "datp is", "is normally", "normally much", "much lower", "lower than", "than that", "that of", "of atp.", "atp. the", "the importance", "importance of", "of this", "this enzyme", "enzyme for", "for purine", "purine synthesis", "synthesis in", "vivo has", "been established", "established by", "by demonstrating", "demonstrating excess", "excess phosphoribosyl", "synthetase activity", "correlated with", "with elevated", "elevated enzyme", "enzyme levels", "levels or", "or altered", "altered enzyme", "enzyme properties", "in individuals", "individuals whose", "whose rates", "rates of", "of uric", "uric acid", "acid production", "production are", "are constitutively", "constitutively abnormally", "abnormally high", "becker and", "and kim", "kim 1987", "roessler et", "al. 1993", "1993 .

              molecular", ".

              molecular cloning", "cloning studies", "studies have", "have revealed", "revealed the", "the existence", "existence of", "of two", "two additional", "additional genes", "genes that", "that encode", "encode phosphoribosyl", "synthetase like", "like proteins", "one widely", "widely expressed", "synthetase 2", "and one", "one whose", "whose expression", "expression appears", "be confined", "confined to", "to the", "the testis", "1 like", "like 1", "taira et", "al. 1989", "1991 .", ". neither", "neither of", "of these", "these proteins", "proteins has", "purified and", "characterized enzymatically", "nor have", "have variations", "variations in", "in the", "the abundance", "abundance or", "or sequence", "sequence of", "of either", "either protein", "protein been", "been associated", "associated with", "with alterations", "alterations in", "in human", "human nucleotide", "nucleotide metabolism", "becker et", "al. 1996", "so their", "their dimerization", "dimerization and", "and ability", "ability to", "to catalyze", "catalyze the", "the synthesis", "synthesis of", "of prpp", "prpp from", "from d", "phosphate are", "are inferred", "inferred here", "here on", "on the", "the basis", "basis of", "of their", "their predicted", "predicted amino", "amino acid", "acid sequence", "sequence similarity", "similarity to", "to phosphoribosyl", "synthetase 1.", "5 phospho alpha", "phospho alpha d", "alpha d ribose", "d ribose 1", "ribose 1 diphosphate", "diphosphate prpp", "prpp is", "is a key", "a key intermediate", "key intermediate in", "intermediate in both", "in both the", "both the de", "the de novo", "de novo and", "novo and salvage", "and salvage pathways", "salvage pathways of", "pathways of purine", "of purine and", "purine and pyrimidine", "and pyrimidine synthesis.", "synthesis. prpp", "prpp and the", "and the enzymatic", "the enzymatic activity", "enzymatic activity responsible", "activity responsible for", "responsible for its", "for its synthesis", "its synthesis were", "synthesis were first", "were first described", "first described by", "described by kornberg", "by kornberg et", "kornberg et al.", "al. 1955", "1955 . the", ". the enzyme", "enzyme phosphoribosyl", "phosphoribosyl pyrophosphate synthetase", "pyrophosphate synthetase 1", "1 has", "has been purified", "been purified from", "purified from human", "from human erythrocytes", "human erythrocytes and", "erythrocytes and characterized", "and characterized biochemically.", "characterized biochemically. the", "biochemically. the purified", "the purified enzyme", "purified enzyme readily", "enzyme readily forms", "readily forms multimers", "multimers its", "its smallest active", "smallest active form", "active form appears", "form appears to", "appears to be", "to be a", "be a dimer", "a dimer and", "dimer and for", "and for simplicity", "for simplicity it", "simplicity it is", "it is annotated", "is annotated as", "annotated as a", "as a dimer", "a dimer here.", "dimer here. it", "here. it specifically", "it specifically catalyzes", "specifically catalyzes the", "catalyzes the transfer", "the transfer of", "transfer of pyrophosphate", "of pyrophosphate from", "pyrophosphate from atp", "from atp or", "atp or datp", "or datp to", "datp to d", "to d ribose", "d ribose 5", "ribose 5 phosphate", "phosphate and", "and has an", "has an absolute", "an absolute requirement", "absolute requirement for", "requirement for mg++", "for mg++ and", "mg++ and orthophosphate", "orthophosphate fox", "fox and kelley", "and kelley 1971", "1971 roth", "roth et al.", "et al. 1974", "al. 1974 .", "1974 . the", ". the significance", "the significance of", "significance of the", "of the reaction", "the reaction with", "reaction with datp", "with datp in", "datp in vivo", "in vivo is", "vivo is unclear", "unclear as", "as the concentration", "the concentration of", "concentration of cytosolic", "of cytosolic datp", "cytosolic datp is", "datp is normally", "is normally much", "normally much lower", "much lower than", "lower than that", "than that of", "that of atp.", "of atp. the", "atp. the importance", "the importance of", "importance of this", "of this enzyme", "this enzyme for", "enzyme for purine", "for purine synthesis", "purine synthesis in", "synthesis in vivo", "in vivo has", "vivo has been", "has been established", "been established by", "established by demonstrating", "by demonstrating excess", "demonstrating excess phosphoribosyl", "excess phosphoribosyl pyrophosphate", "pyrophosphate synthetase activity", "activity correlated", "correlated with elevated", "with elevated enzyme", "elevated enzyme levels", "enzyme levels or", "levels or altered", "or altered enzyme", "altered enzyme properties", "properties in", "in individuals whose", "individuals whose rates", "whose rates of", "rates of uric", "of uric acid", "uric acid production", "acid production are", "production are constitutively", "are constitutively abnormally", "constitutively abnormally high", "high becker", "becker and kim", "and kim 1987", "1987 roessler", "roessler et al.", "et al. 1993", "al. 1993 .

              molecular", "1993 .

              molecular cloning", ".

              molecular cloning studies", "cloning studies have", "studies have revealed", "have revealed the", "revealed the existence", "the existence of", "existence of two", "of two additional", "two additional genes", "additional genes that", "genes that encode", "that encode phosphoribosyl", "encode phosphoribosyl pyrophosphate", "pyrophosphate synthetase like", "synthetase like proteins", "proteins one", "one widely expressed", "expressed phosphoribosyl", "pyrophosphate synthetase 2", "2 and", "and one whose", "one whose expression", "whose expression appears", "expression appears to", "to be confined", "be confined to", "confined to the", "to the testis", "testis phosphoribosyl", "synthetase 1 like", "1 like 1", "taira et al.", "et al. 1989", "1989 1991", "1991 . neither", ". neither of", "neither of these", "of these proteins", "these proteins has", "proteins has been", "been purified and", "purified and characterized", "and characterized enzymatically", "enzymatically nor", "nor have variations", "have variations in", "variations in the", "in the abundance", "the abundance or", "abundance or sequence", "or sequence of", "sequence of either", "of either protein", "either protein been", "protein been associated", "been associated with", "associated with alterations", "with alterations in", "alterations in human", "in human nucleotide", "human nucleotide metabolism", "metabolism roessler", "1993 becker", "becker et al.", "et al. 1996", "so their dimerization", "their dimerization and", "dimerization and ability", "and ability to", "ability to catalyze", "to catalyze the", "catalyze the synthesis", "the synthesis of", "synthesis of prpp", "of prpp from", "prpp from d", "from d ribose", "5 phosphate are", "phosphate are inferred", "are inferred here", "inferred here on", "here on the", "on the basis", "the basis of", "basis of their", "of their predicted", "their predicted amino", "predicted amino acid", "amino acid sequence", "acid sequence similarity", "sequence similarity to", "similarity to phosphoribosyl", "to phosphoribosyl pyrophosphate", "pyrophosphate synthetase 1.", "5 phospho alpha d", "phospho alpha d ribose", "alpha d ribose 1", "d ribose 1 diphosphate", "1 diphosphate prpp", "prpp is a", "is a key intermediate", "a key intermediate in", "key intermediate in both", "intermediate in both the", "in both the de", "both the de novo", "the de novo and", "de novo and salvage", "novo and salvage pathways", "and salvage pathways of", "salvage pathways of purine", "pathways of purine and", "of purine and pyrimidine", "purine and pyrimidine synthesis.", "pyrimidine synthesis. prpp", "synthesis. prpp and", "prpp and the enzymatic", "and the enzymatic activity", "the enzymatic activity responsible", "enzymatic activity responsible for", "activity responsible for its", "responsible for its synthesis", "for its synthesis were", "its synthesis were first", "synthesis were first described", "were first described by", "first described by kornberg", "described by kornberg et", "by kornberg et al.", "et al. 1955", "al. 1955 .", "1955 . the enzyme", "the enzyme phosphoribosyl", "enzyme phosphoribosyl pyrophosphate", "phosphoribosyl pyrophosphate synthetase 1", "synthetase 1 has", "1 has been", "has been purified from", "been purified from human", "purified from human erythrocytes", "from human erythrocytes and", "human erythrocytes and characterized", "erythrocytes and characterized biochemically.", "and characterized biochemically. the", "characterized biochemically. the purified", "biochemically. the purified enzyme", "the purified enzyme readily", "purified enzyme readily forms", "enzyme readily forms multimers", "forms multimers its", "multimers its smallest", "its smallest active form", "smallest active form appears", "active form appears to", "form appears to be", "appears to be a", "to be a dimer", "be a dimer and", "a dimer and for", "dimer and for simplicity", "and for simplicity it", "for simplicity it is", "simplicity it is annotated", "it is annotated as", "is annotated as a", "annotated as a dimer", "as a dimer here.", "a dimer here. it", "dimer here. it specifically", "here. it specifically catalyzes", "it specifically catalyzes the", "specifically catalyzes the transfer", "catalyzes the transfer of", "the transfer of pyrophosphate", "transfer of pyrophosphate from", "of pyrophosphate from atp", "pyrophosphate from atp or", "from atp or datp", "atp or datp to", "or datp to d", "datp to d ribose", "to d ribose 5", "d ribose 5 phosphate", "5 phosphate and", "phosphate and has", "and has an absolute", "has an absolute requirement", "an absolute requirement for", "absolute requirement for mg++", "requirement for mg++ and", "for mg++ and orthophosphate", "and orthophosphate fox", "orthophosphate fox and", "fox and kelley 1971", "kelley 1971 roth", "1971 roth et", "roth et al. 1974", "et al. 1974 .", "al. 1974 . the", "1974 . the significance", ". the significance of", "the significance of the", "significance of the reaction", "of the reaction with", "the reaction with datp", "reaction with datp in", "with datp in vivo", "datp in vivo is", "in vivo is unclear", "is unclear as", "unclear as the", "as the concentration of", "the concentration of cytosolic", "concentration of cytosolic datp", "of cytosolic datp is", "cytosolic datp is normally", "datp is normally much", "is normally much lower", "normally much lower than", "much lower than that", "lower than that of", "than that of atp.", "that of atp. the", "of atp. the importance", "atp. the importance of", "the importance of this", "importance of this enzyme", "of this enzyme for", "this enzyme for purine", "enzyme for purine synthesis", "for purine synthesis in", "purine synthesis in vivo", "synthesis in vivo has", "in vivo has been", "vivo has been established", "has been established by", "been established by demonstrating", "established by demonstrating excess", "by demonstrating excess phosphoribosyl", "demonstrating excess phosphoribosyl pyrophosphate", "excess phosphoribosyl pyrophosphate synthetase", "phosphoribosyl pyrophosphate synthetase activity", "synthetase activity correlated", "activity correlated with", "correlated with elevated enzyme", "with elevated enzyme levels", "elevated enzyme levels or", "enzyme levels or altered", "levels or altered enzyme", "or altered enzyme properties", "enzyme properties in", "properties in individuals", "in individuals whose rates", "individuals whose rates of", "whose rates of uric", "rates of uric acid", "of uric acid production", "uric acid production are", "acid production are constitutively", "production are constitutively abnormally", "are constitutively abnormally high", "abnormally high becker", "high becker and", "becker and kim 1987", "kim 1987 roessler", "1987 roessler et", "roessler et al. 1993", "et al. 1993 .

              molecular", "al. 1993 .

              molecular cloning", "1993 .

              molecular cloning studies", ".

              molecular cloning studies have", "cloning studies have revealed", "studies have revealed the", "have revealed the existence", "revealed the existence of", "the existence of two", "existence of two additional", "of two additional genes", "two additional genes that", "additional genes that encode", "genes that encode phosphoribosyl", "that encode phosphoribosyl pyrophosphate", "encode phosphoribosyl pyrophosphate synthetase", "phosphoribosyl pyrophosphate synthetase like", "pyrophosphate synthetase like proteins", "like proteins one", "proteins one widely", "widely expressed phosphoribosyl", "expressed phosphoribosyl pyrophosphate", "phosphoribosyl pyrophosphate synthetase 2", "synthetase 2 and", "2 and one", "and one whose expression", "one whose expression appears", "whose expression appears to", "expression appears to be", "appears to be confined", "to be confined to", "be confined to the", "confined to the testis", "the testis phosphoribosyl", "testis phosphoribosyl pyrophosphate", "pyrophosphate synthetase 1 like", "synthetase 1 like 1", "1 taira", "taira et al. 1989", "al. 1989 1991", "1989 1991 .", "1991 . neither of", ". neither of these", "neither of these proteins", "of these proteins has", "these proteins has been", "proteins has been purified", "has been purified and", "been purified and characterized", "purified and characterized enzymatically", "characterized enzymatically nor", "enzymatically nor have", "nor have variations in", "have variations in the", "variations in the abundance", "in the abundance or", "the abundance or sequence", "abundance or sequence of", "or sequence of either", "sequence of either protein", "of either protein been", "either protein been associated", "protein been associated with", "been associated with alterations", "associated with alterations in", "with alterations in human", "alterations in human nucleotide", "in human nucleotide metabolism", "nucleotide metabolism roessler", "metabolism roessler et", "al. 1993 becker", "1993 becker et", "becker et al. 1996", "1996 so", "so their dimerization and", "their dimerization and ability", "dimerization and ability to", "and ability to catalyze", "ability to catalyze the", "to catalyze the synthesis", "catalyze the synthesis of", "the synthesis of prpp", "synthesis of prpp from", "of prpp from d", "prpp from d ribose", "from d ribose 5", "ribose 5 phosphate are", "5 phosphate are inferred", "phosphate are inferred here", "are inferred here on", "inferred here on the", "here on the basis", "on the basis of", "the basis of their", "basis of their predicted", "of their predicted amino", "their predicted amino acid", "predicted amino acid sequence", "amino acid sequence similarity", "acid sequence similarity to", "sequence similarity to phosphoribosyl", "similarity to phosphoribosyl pyrophosphate", "to phosphoribosyl pyrophosphate synthetase", "phosphoribosyl pyrophosphate synthetase 1.", "5 phospho alpha d ribose", "phospho alpha d ribose 1", "alpha d ribose 1 diphosphate", "ribose 1 diphosphate prpp", "diphosphate prpp is", "prpp is a key", "is a key intermediate in", "a key intermediate in both", "key intermediate in both the", "intermediate in both the de", "in both the de novo", "both the de novo and", "the de novo and salvage", "de novo and salvage pathways", "novo and salvage pathways of", "and salvage pathways of purine", "salvage pathways of purine and", "pathways of purine and pyrimidine", "of purine and pyrimidine synthesis.", "and pyrimidine synthesis. prpp", "pyrimidine synthesis. prpp and", "synthesis. prpp and the", "prpp and the enzymatic activity", "and the enzymatic activity responsible", "the enzymatic activity responsible for", "enzymatic activity responsible for its", "activity responsible for its synthesis", "responsible for its synthesis were", "for its synthesis were first", "its synthesis were first described", "synthesis were first described by", "were first described by kornberg", "first described by kornberg et", "described by kornberg et al.", "kornberg et al. 1955", "et al. 1955 .", "al. 1955 . the", ". the enzyme phosphoribosyl", "the enzyme phosphoribosyl pyrophosphate", "enzyme phosphoribosyl pyrophosphate synthetase", "pyrophosphate synthetase 1 has", "synthetase 1 has been", "1 has been purified", "has been purified from human", "been purified from human erythrocytes", "purified from human erythrocytes and", "from human erythrocytes and characterized", "human erythrocytes and characterized biochemically.", "erythrocytes and characterized biochemically. the", "and characterized biochemically. the purified", "characterized biochemically. the purified enzyme", "biochemically. the purified enzyme readily", "the purified enzyme readily forms", "purified enzyme readily forms multimers", "readily forms multimers its", "forms multimers its smallest", "multimers its smallest active", "its smallest active form appears", "smallest active form appears to", "active form appears to be", "form appears to be a", "appears to be a dimer", "to be a dimer and", "be a dimer and for", "a dimer and for simplicity", "dimer and for simplicity it", "and for simplicity it is", "for simplicity it is annotated", "simplicity it is annotated as", "it is annotated as a", "is annotated as a dimer", "annotated as a dimer here.", "as a dimer here. it", "a dimer here. it specifically", "dimer here. it specifically catalyzes", "here. it specifically catalyzes the", "it specifically catalyzes the transfer", "specifically catalyzes the transfer of", "catalyzes the transfer of pyrophosphate", "the transfer of pyrophosphate from", "transfer of pyrophosphate from atp", "of pyrophosphate from atp or", "pyrophosphate from atp or datp", "from atp or datp to", "atp or datp to d", "or datp to d ribose", "datp to d ribose 5", "to d ribose 5 phosphate", "ribose 5 phosphate and", "5 phosphate and has", "phosphate and has an", "and has an absolute requirement", "has an absolute requirement for", "an absolute requirement for mg++", "absolute requirement for mg++ and", "requirement for mg++ and orthophosphate", "mg++ and orthophosphate fox", "and orthophosphate fox and", "orthophosphate fox and kelley", "and kelley 1971 roth", "kelley 1971 roth et", "1971 roth et al.", "roth et al. 1974 .", "et al. 1974 . the", "al. 1974 . the significance", "1974 . the significance of", ". the significance of the", "the significance of the reaction", "significance of the reaction with", "of the reaction with datp", "the reaction with datp in", "reaction with datp in vivo", "with datp in vivo is", "datp in vivo is unclear", "vivo is unclear as", "is unclear as the", "unclear as the concentration", "as the concentration of cytosolic", "the concentration of cytosolic datp", "concentration of cytosolic datp is", "of cytosolic datp is normally", "cytosolic datp is normally much", "datp is normally much lower", "is normally much lower than", "normally much lower than that", "much lower than that of", "lower than that of atp.", "than that of atp. the", "that of atp. the importance", "of atp. the importance of", "atp. the importance of this", "the importance of this enzyme", "importance of this enzyme for", "of this enzyme for purine", "this enzyme for purine synthesis", "enzyme for purine synthesis in", "for purine synthesis in vivo", "purine synthesis in vivo has", "synthesis in vivo has been", "in vivo has been established", "vivo has been established by", "has been established by demonstrating", "been established by demonstrating excess", "established by demonstrating excess phosphoribosyl", "by demonstrating excess phosphoribosyl pyrophosphate", "demonstrating excess phosphoribosyl pyrophosphate synthetase", "excess phosphoribosyl pyrophosphate synthetase activity", "pyrophosphate synthetase activity correlated", "synthetase activity correlated with", "activity correlated with elevated", "correlated with elevated enzyme levels", "with elevated enzyme levels or", "elevated enzyme levels or altered", "enzyme levels or altered enzyme", "levels or altered enzyme properties", "altered enzyme properties in", "enzyme properties in individuals", "properties in individuals whose", "in individuals whose rates of", "individuals whose rates of uric", "whose rates of uric acid", "rates of uric acid production", "of uric acid production are", "uric acid production are constitutively", "acid production are constitutively abnormally", "production are constitutively abnormally high", "constitutively abnormally high becker", "abnormally high becker and", "high becker and kim", "and kim 1987 roessler", "kim 1987 roessler et", "1987 roessler et al.", "roessler et al. 1993 .

              molecular", "et al. 1993 .

              molecular cloning", "al. 1993 .

              molecular cloning studies", "1993 .

              molecular cloning studies have", ".

              molecular cloning studies have revealed", "cloning studies have revealed the", "studies have revealed the existence", "have revealed the existence of", "revealed the existence of two", "the existence of two additional", "existence of two additional genes", "of two additional genes that", "two additional genes that encode", "additional genes that encode phosphoribosyl", "genes that encode phosphoribosyl pyrophosphate", "that encode phosphoribosyl pyrophosphate synthetase", "encode phosphoribosyl pyrophosphate synthetase like", "phosphoribosyl pyrophosphate synthetase like proteins", "synthetase like proteins one", "like proteins one widely", "proteins one widely expressed", "one widely expressed phosphoribosyl", "widely expressed phosphoribosyl pyrophosphate", "expressed phosphoribosyl pyrophosphate synthetase", "pyrophosphate synthetase 2 and", "synthetase 2 and one", "2 and one whose", "and one whose expression appears", "one whose expression appears to", "whose expression appears to be", "expression appears to be confined", "appears to be confined to", "to be confined to the", "be confined to the testis", "to the testis phosphoribosyl", "the testis phosphoribosyl pyrophosphate", "testis phosphoribosyl pyrophosphate synthetase", "phosphoribosyl pyrophosphate synthetase 1 like", "pyrophosphate synthetase 1 like 1", "like 1 taira", "1 taira et", "et al. 1989 1991", "al. 1989 1991 .", "1989 1991 . neither", "1991 . neither of these", ". neither of these proteins", "neither of these proteins has", "of these proteins has been", "these proteins has been purified", "proteins has been purified and", "has been purified and characterized", "been purified and characterized enzymatically", "and characterized enzymatically nor", "characterized enzymatically nor have", "enzymatically nor have variations", "nor have variations in the", "have variations in the abundance", "variations in the abundance or", "in the abundance or sequence", "the abundance or sequence of", "abundance or sequence of either", "or sequence of either protein", "sequence of either protein been", "of either protein been associated", "either protein been associated with", "protein been associated with alterations", "been associated with alterations in", "associated with alterations in human", "with alterations in human nucleotide", "alterations in human nucleotide metabolism", "human nucleotide metabolism roessler", "nucleotide metabolism roessler et", "metabolism roessler et al.", "et al. 1993 becker", "al. 1993 becker et", "1993 becker et al.", "al. 1996 so", "1996 so their", "so their dimerization and ability", "their dimerization and ability to", "dimerization and ability to catalyze", "and ability to catalyze the", "ability to catalyze the synthesis", "to catalyze the synthesis of", "catalyze the synthesis of prpp", "the synthesis of prpp from", "synthesis of prpp from d", "of prpp from d ribose", "prpp from d ribose 5", "from d ribose 5 phosphate", "d ribose 5 phosphate are", "ribose 5 phosphate are inferred", "5 phosphate are inferred here", "phosphate are inferred here on", "are inferred here on the", "inferred here on the basis", "here on the basis of", "on the basis of their", "the basis of their predicted", "basis of their predicted amino", "of their predicted amino acid", "their predicted amino acid sequence", "predicted amino acid sequence similarity", "amino acid sequence similarity to", "acid sequence similarity to phosphoribosyl", "sequence similarity to phosphoribosyl pyrophosphate", "similarity to phosphoribosyl pyrophosphate synthetase", "to phosphoribosyl pyrophosphate synthetase 1." ] }, { "record_id": "GLY_000594_1_1473", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "73930", "r hsa", "hsa 73930", "r hsa 73930" ] }, { "record_id": "GLY_000594_1_1473", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "abasic sugar", "sugar phosphate", "phosphate removal", "removal via", "via the", "the single", "single nucleotide", "nucleotide replacement", "replacement pathway", "abasic sugar phosphate", "sugar phosphate removal", "phosphate removal via", "removal via the", "via the single", "the single nucleotide", "single nucleotide replacement", "nucleotide replacement pathway", "abasic sugar phosphate removal", "sugar phosphate removal via", "phosphate removal via the", "removal via the single", "via the single nucleotide", "the single nucleotide replacement", "single nucleotide replacement pathway", "abasic sugar phosphate removal via", "sugar phosphate removal via the", "phosphate removal via the single", "removal via the single nucleotide", "via the single nucleotide replacement", "the single nucleotide replacement pathway", "pathway requires", "requires displacement", "displacement of", "of dna", "dna glycosylase", "glycosylase by", "by apex1", "apex1 mediated", "mediated endonucleolytic", "endonucleolytic cleavage", 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"the abasic sugar", "phosphate 5'drp", "5'drp residue", "residue at the", "at the strand", "the strand break", "break lindahl", "lindahl and wood", "wood 1999", "nucleotide replacement pathway requires", "replacement pathway requires displacement", "pathway requires displacement of", "requires displacement of dna", "displacement of dna glycosylase", "of dna glycosylase by", "dna glycosylase by apex1", "by apex1 apex1", "apex1 apex1 mediated", "apex1 mediated endonucleolytic cleavage", "mediated endonucleolytic cleavage at", "endonucleolytic cleavage at the", "cleavage at the 5'", "at the 5' side", "the 5' side of", "5' side of the", "side of the base", "of the base free", "the base free deoxyribose", "base free deoxyribose residue", "deoxyribose residue recruitment", "residue recruitment of", "recruitment of polb to", "of polb to the", "polb to the ap", "to the ap site", "the ap site and", "ap site and excision", "site and excision of", "and excision of the", "excision of the abasic", "of the abasic sugar", "the abasic sugar phosphate", "sugar phosphate 5'drp", "5'drp residue at", "residue at the strand", "at the strand break", "strand break lindahl", "break lindahl and", "and wood 1999", "wood 1999 .", "single nucleotide replacement pathway requires", "nucleotide replacement pathway requires displacement", "replacement pathway requires displacement of", "pathway requires displacement of dna", "requires displacement of dna glycosylase", "displacement of dna glycosylase by", "of dna glycosylase by apex1", "glycosylase by apex1 apex1", "by apex1 apex1 mediated", "apex1 apex1 mediated endonucleolytic", "apex1 mediated endonucleolytic cleavage at", "mediated endonucleolytic cleavage at the", "endonucleolytic cleavage at the 5'", "cleavage at the 5' side", "at the 5' side of", "the 5' side of the", "5' side of the base", "side of the base free", "of the base free deoxyribose", "the base free deoxyribose residue", "free deoxyribose residue recruitment", "deoxyribose residue recruitment of", "residue recruitment of polb", "recruitment of polb to the", "of polb to the ap", "polb to the ap site", "to the ap site and", "the ap site and excision", "ap site and excision of", "site and excision of the", "and excision of the abasic", "excision of the abasic sugar", "of the abasic sugar phosphate", "abasic sugar phosphate 5'drp", "phosphate 5'drp residue", "5'drp residue at the", "residue at the strand break", "the strand break lindahl", "strand break lindahl and", "break lindahl and wood", "lindahl and wood 1999", "and wood 1999 ." ] }, { "record_id": "GLY_000594_1_1474", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75108", "r hsa", "hsa 75108", "r hsa 75108" ] }, { "record_id": "GLY_000594_1_1474", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "myristolyation of", "of bid", "bid and", "and translocation", "translocation to", "to mitochondria", "activation 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event", "event may", "may act", "act as", "as a", "a link", "link between", "between extrinsic", "caspase 8/10", "8/10 dependent", "and intrinsic", "bcl 2", "2 inhibitable", "pathways although", "although some", "some evidences", "evidences from", "from mouse", "mouse genetic", "genetic experiments", "experiments suggest", "suggest the", "the contrary.", "contrary. it", "it has", "has been", "been suggested", "suggested that", "that the", "the death", "death signals", "signals from", "from the", "the extrinsic", "extrinsic or", "or death", "death receptor", "receptor pathway", "pathway may", "may get", "get amplified", "amplified by", "by the", "the mechanisms", "mechanisms of", "of intrinsic", "intrinsic pathway", "pathway and", "and that", "that this", "this functional", "functional loop", "loop may", "may be", "be enabled", "enabled by", "the molecules", "molecules like", "like tbid", "truncated bid", "bid .
              ", ".
              cleavage", "cleavage of", "bid to", "to tbid", "tbid can", "can also", "also be", "be achieved", "achieved by", "by granzyme", "granzyme b.", "b. the", "the truncated", "truncated protein", "protein is", "is myristoylated", "myristoylated and", "and translocates", "translocates to", "to mitochondria.", "bid may promote", "may promote cell", "promote cell death", "cell death by", "death by activating", "by activating bax", "activating bax and", "bax and bak", "and bak while", "bak while inactivating", "while inactivating anti", "inactivating anti apoptotic", "anti apoptotic proteins.", "apoptotic proteins. the", "proteins. the engagement", "the engagement of", "engagement of cell", "of cell surface", "cell surface receptors", "surface receptors activates", "receptors activates the", "activates the caspase", "the caspase 8", "8 a", "heterodimer that", "that cleaves bid", "cleaves bid in", "bid in its", "in its amino", "its amino terminal", "amino terminal region.", "terminal region. this", "region. this particular", "this particular event", "particular event may", "event may act", "may act as", "act as a", "as a link", "a link between", "link between extrinsic", "extrinsic caspase", "caspase 8/10 dependent", "dependent and", "intrinsic bcl", "bcl 2 inhibitable", "inhibitable pathways", "pathways although some", "although some evidences", "some evidences from", "evidences from mouse", "from mouse genetic", "mouse genetic experiments", "genetic experiments suggest", "experiments suggest the", "suggest the contrary.", "the contrary. it", "contrary. it has", "it has been", "has been suggested", "been suggested that", "suggested that the", "that the death", "the death signals", "death signals from", "signals from the", "from the extrinsic", "the extrinsic or", "extrinsic or death", "or death receptor", "death receptor pathway", "receptor pathway may", "pathway may get", "may get amplified", "get amplified by", "amplified by the", "by the mechanisms", "the mechanisms of", "mechanisms of intrinsic", "of intrinsic pathway", "intrinsic pathway and", "pathway and that", "and that this", "that this functional", "this functional loop", "functional loop may", "loop may be", "may be enabled", "be enabled by", "enabled by the", "by the molecules", "the molecules like", "molecules like tbid", "tbid truncated", "truncated bid .
              ", "bid .
              cleavage", ".
              cleavage of", "cleavage of bid", "of bid to", "bid to tbid", "to tbid can", "tbid can also", "can also be", "also be achieved", "be achieved by", "achieved by granzyme", "by granzyme b.", "granzyme b. the", "b. the truncated", "the truncated protein", "truncated protein is", "protein is myristoylated", "is myristoylated and", "myristoylated and translocates", "and translocates to", "translocates to mitochondria.", "bid may promote cell", "may promote cell death", "promote cell death by", "cell death by activating", "death by activating bax", "by activating bax and", "activating bax and bak", "bax and bak while", "and bak while inactivating", "bak while inactivating anti", "while inactivating anti apoptotic", "inactivating anti apoptotic proteins.", "anti apoptotic proteins. the", "apoptotic proteins. the engagement", "proteins. the engagement of", "the engagement of cell", "engagement of cell surface", "of cell surface receptors", "cell surface receptors activates", "surface receptors activates the", "receptors activates the caspase", "activates the caspase 8", "caspase 8 a", "8 a heterodimer", "a heterodimer that", "heterodimer that cleaves", "that cleaves bid in", "cleaves bid in its", "bid in its amino", "in its amino terminal", "its amino terminal region.", "amino terminal region. this", "terminal region. this particular", "region. this particular event", "this particular event may", "particular event may act", "event may act as", "may act as a", "act as a link", "as a link between", "a link between extrinsic", "between extrinsic caspase", "extrinsic caspase 8/10", "8/10 dependent and", "dependent and intrinsic", "and intrinsic bcl", "intrinsic bcl 2", "2 inhibitable pathways", "inhibitable pathways although", "pathways although some evidences", "although some evidences from", "some evidences from mouse", "evidences from mouse genetic", "from mouse genetic experiments", "mouse genetic experiments suggest", "genetic experiments suggest the", "experiments suggest the contrary.", "suggest the contrary. it", "the contrary. it has", "contrary. it has been", "it has been suggested", "has been suggested that", "been suggested that the", "suggested that the death", "that the death signals", "the death signals from", "death signals from the", "signals from the extrinsic", "from the extrinsic or", "the extrinsic or death", "extrinsic or death receptor", "or death receptor pathway", "death receptor pathway may", "receptor pathway may get", "pathway may get amplified", "may get amplified by", "get amplified by the", "amplified by the mechanisms", "by the mechanisms of", "the mechanisms of intrinsic", "mechanisms of intrinsic pathway", "of intrinsic pathway and", "intrinsic pathway and that", "pathway and that this", "and that this functional", "that this functional loop", "this functional loop may", "functional loop may be", "loop may be enabled", "may be enabled by", "be enabled by the", "enabled by the molecules", "by the molecules like", "the molecules like tbid", "like tbid truncated", "tbid truncated bid", "truncated bid .
              cleavage", "bid .
              cleavage of", ".
              cleavage of bid", "cleavage of bid to", "of bid to tbid", "bid to tbid can", "to tbid can also", "tbid can also be", "can also be achieved", "also be achieved by", "be achieved by granzyme", "achieved by granzyme b.", "by granzyme b. the", "granzyme b. the truncated", "b. the truncated protein", "the truncated protein is", "truncated protein is myristoylated", "protein is myristoylated and", "is myristoylated and translocates", "myristoylated and translocates to", "and translocates to mitochondria.", "bid may promote cell death", "may promote cell death by", "promote cell death by activating", "cell death by activating bax", "death by activating bax and", "by activating bax and bak", "activating bax and bak while", "bax and bak while inactivating", "and bak while inactivating anti", "bak while inactivating anti apoptotic", "while inactivating anti apoptotic proteins.", "inactivating anti apoptotic proteins. the", "anti apoptotic proteins. the engagement", "apoptotic proteins. the engagement of", "proteins. the engagement of cell", "the engagement of cell surface", "engagement of cell surface receptors", "of cell surface receptors activates", "cell surface receptors activates the", "surface receptors activates the caspase", "receptors activates the caspase 8", "the caspase 8 a", "caspase 8 a heterodimer", "a heterodimer that cleaves", "heterodimer that cleaves bid", "that cleaves bid in its", "cleaves bid in its amino", "bid in its amino terminal", "in its amino terminal region.", "its amino terminal region. this", "amino terminal region. this particular", "terminal region. this particular event", "region. this particular event may", "this particular event may act", "particular event may act as", "event may act as a", "may act as a link", "act as a link between", "as a link between extrinsic", "link between extrinsic caspase", "between extrinsic caspase 8/10", "extrinsic caspase 8/10 dependent", "caspase 8/10 dependent and", "8/10 dependent and intrinsic", "and intrinsic bcl 2", "intrinsic bcl 2 inhibitable", "bcl 2 inhibitable pathways", "2 inhibitable pathways although", "inhibitable pathways although some", "pathways although some evidences from", "although some evidences from mouse", "some evidences from mouse genetic", "evidences from mouse genetic experiments", "from mouse genetic experiments suggest", "mouse genetic experiments suggest the", "genetic experiments suggest the contrary.", "experiments suggest the contrary. it", "suggest the contrary. it has", "the contrary. it has been", "contrary. it has been suggested", "it has been suggested that", "has been suggested that the", "been suggested that the death", "suggested that the death signals", "that the death signals from", "the death signals from the", "death signals from the extrinsic", "signals from the extrinsic or", "from the extrinsic or death", "the extrinsic or death receptor", "extrinsic or death receptor pathway", "or death receptor pathway may", "death receptor pathway may get", "receptor pathway may get amplified", "pathway may get amplified by", "may get amplified by the", "get amplified by the mechanisms", "amplified by the mechanisms of", "by the mechanisms of intrinsic", "the mechanisms of intrinsic pathway", "mechanisms of intrinsic pathway and", "of intrinsic pathway and that", "intrinsic pathway and that this", "pathway and that this functional", "and that this functional loop", "that this functional loop may", "this functional loop may be", "functional loop may be enabled", "loop may be enabled by", "may be enabled by the", "be enabled by the molecules", "enabled by the molecules like", "by the molecules like tbid", "molecules like tbid truncated", "like tbid truncated bid", "tbid truncated bid .
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these molecules for the", "these molecules for the beta", "molecules for the beta oxidation", "for the beta oxidation pathway.", "the beta oxidation pathway. the", "beta oxidation pathway. the further", "oxidation pathway. the further processing", "pathway. the further processing of", "the further processing of these", "further processing of these intermediates", "processing of these intermediates requires", "of these intermediates requires additional", "these intermediates requires additional enzymes", "requires additional enzymes depending", "additional enzymes depending on", "enzymes depending on the", "depending on the position of", "on the position of the", "the position of the double", "position of the double bonds", "of the double bonds in", "the double bonds in the", "double bonds in the original", "bonds in the original fatty", "in the original fatty acids.", "the original fatty acids. described", "original fatty acids. described here", "fatty acids. described here is", "acids. described here is the", "described here is the beta", "here is the beta oxidation", "is the beta oxidation of", "the beta oxidation of linoleoyl", "beta oxidation of linoleoyl coa." ] }, { "record_id": "GLY_000594_1_1480", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77305", "r hsa", "hsa 77305", "r hsa 77305" ] }, { "record_id": "GLY_000594_1_1480", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of palmitoyl", "palmitoyl coa", "coa to", "to myristoyl", "myristoyl coa", "beta oxidation of", "oxidation of palmitoyl", "of palmitoyl coa", "palmitoyl coa to", "coa to myristoyl", "to myristoyl coa", "beta oxidation of palmitoyl", "oxidation of palmitoyl coa", "of palmitoyl coa to", "palmitoyl coa to myristoyl", "coa to myristoyl coa", "beta oxidation of palmitoyl coa", "oxidation of palmitoyl coa to", "of palmitoyl coa to myristoyl", "palmitoyl coa to myristoyl coa", "this first", "first pass", "pass through", "through the", "the beta", "oxidation spiral", "spiral starts", "starts with", "with the", "the saturated", "saturated fatty", "fatty acid", "acid palmitoyl", "coa and", "and produces", "produces myristoyl", "myristoyl coa.", "coa. four", "four enzymatic", "enzymatic steps", "steps are", "are required", "starting with", "with vlcad", "vlcad coa", "coa dehydrogenase", "very long", "long chain", "followed by", "by three", "three enzymatic", "enoyl coa", "coa hydratase", "3 hydroxyacyl", "hydroxyacyl coa", "and ketoacyl", "ketoacyl coa", "coa thiolase", "thiolase activities", "all present", "present in", "in the", "the mitochondrial", "mitochondrial membrane", "membrane associated", "associated trifunctional", "trifunctional protein.", "this first pass", "first pass through", "pass through the", "through the beta", "the beta oxidation", "beta oxidation spiral", "oxidation spiral starts", "spiral starts with", "starts with the", "with the saturated", "the saturated fatty", "saturated fatty acid", "fatty acid palmitoyl", "acid palmitoyl coa", "palmitoyl coa and", "coa and produces", "and produces myristoyl", "produces myristoyl coa.", "myristoyl coa. four", "coa. four enzymatic", "four enzymatic steps", "enzymatic steps are", "steps are required", "required starting", "starting with vlcad", "with vlcad coa", "vlcad coa dehydrogenase", "dehydrogenase very", "very long chain", "chain activity", "activity followed", "followed by three", "by three enzymatic", "three enzymatic steps", "steps enoyl", "enoyl coa hydratase", "hydratase 3", "3 hydroxyacyl coa", "hydroxyacyl coa dehydrogenase", "dehydrogenase and", "and ketoacyl coa", "ketoacyl coa thiolase", "coa thiolase activities", "activities all", "all present in", "present in the", "in the mitochondrial", "the mitochondrial membrane", "mitochondrial membrane associated", "membrane associated trifunctional", "associated trifunctional protein.", "this first pass through", "first pass through the", "pass through the beta", "through the beta oxidation", "the beta oxidation spiral", "beta oxidation spiral starts", "oxidation spiral starts with", "spiral starts with the", "starts with the saturated", "with the saturated fatty", "the saturated fatty acid", "saturated fatty acid palmitoyl", "fatty acid palmitoyl coa", "acid palmitoyl coa and", "palmitoyl coa and produces", "coa and produces myristoyl", "and produces myristoyl coa.", "produces myristoyl coa. four", "myristoyl coa. four enzymatic", "coa. four enzymatic steps", "four enzymatic steps are", "enzymatic steps are required", "are required starting", "required starting with", "starting with vlcad coa", "with vlcad coa dehydrogenase", "coa dehydrogenase very", "dehydrogenase very long", "long chain activity", "activity followed by", "followed by three enzymatic", "by three enzymatic steps", "enzymatic steps enoyl", "steps enoyl coa", "coa hydratase 3", "hydratase 3 hydroxyacyl", "3 hydroxyacyl coa dehydrogenase", "coa dehydrogenase and", "dehydrogenase and ketoacyl", "and ketoacyl coa thiolase", "ketoacyl coa thiolase activities", "thiolase activities all", "activities all present", "all present in the", "present in the mitochondrial", "in the mitochondrial membrane", "the mitochondrial membrane associated", "mitochondrial membrane associated trifunctional", "membrane associated trifunctional protein.", "this first pass through the", "first pass through the beta", "pass through the beta oxidation", "through the beta oxidation spiral", "the beta oxidation spiral starts", "beta oxidation spiral starts with", "oxidation spiral starts with the", "spiral starts with the saturated", "starts with the saturated fatty", "with the saturated fatty acid", "the saturated fatty acid palmitoyl", "saturated fatty acid palmitoyl coa", "fatty acid palmitoyl coa and", "acid palmitoyl coa and produces", "palmitoyl coa and produces myristoyl", "coa and produces myristoyl coa.", "and 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the mitochondrial membrane", "in the mitochondrial membrane associated", "the mitochondrial membrane associated trifunctional", "mitochondrial membrane associated trifunctional protein." ] }, { "record_id": "GLY_000594_1_1481", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77346", "r hsa", "hsa 77346", "r hsa 77346" ] }, { "record_id": "GLY_000594_1_1481", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of decanoyl", "decanoyl coa", "coa to", "to octanoyl", "octanoyl coa", "coa coa", "beta oxidation of", "oxidation of decanoyl", "of decanoyl coa", "decanoyl coa to", "coa to octanoyl", "to octanoyl coa", "octanoyl coa coa", "beta oxidation of decanoyl", "oxidation of decanoyl coa", "of decanoyl coa to", "decanoyl coa to octanoyl", "coa to octanoyl coa", "to octanoyl coa coa", "beta oxidation of decanoyl coa", "oxidation of decanoyl coa to", "of decanoyl coa to 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"membrane associated", "associated trifunctional", "trifunctional protein.", "protein. note", "note that", "that the", "of schad", "schad is", "is not", "not actually", "actually limited", "limited to", "to short", "chain fatty", "fatty acids", "in fact", "fact schad", "schad has", "has a", "a broad", "broad substrate", "substrate specificity.", "the fourth pass", "fourth pass through", "pass through the", "through the beta", "the beta oxidation", "beta oxidation spiral", "oxidation spiral picks", "spiral picks up", "picks up where", "up where the", "where the last", "the last left", "last left off", "left off with", "off with the", "with the saturated", "the saturated fatty", "saturated fatty acid", "fatty acid decanoyl", "acid decanoyl coa", "decanoyl coa and", "coa and produces", "and produces octanoyl", "produces octanoyl coa.", "octanoyl coa. four", "coa. four enzymatic", "four enzymatic steps", "enzymatic steps are", "steps are required", "are required starting", "required 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"of schad is", "schad is not", "is not actually", "not actually limited", "actually limited to", "limited to short", "to short chain", "short chain fatty", "chain fatty acids", "acids in", "in fact schad", "fact schad has", "schad has a", "has a broad", "a broad substrate", "broad substrate specificity.", "the fourth pass through", "fourth pass through the", "pass through the beta", "through the beta oxidation", "the beta oxidation spiral", "beta oxidation spiral picks", "oxidation spiral picks up", "spiral picks up where", "picks up where the", "up where the last", "where the last left", "the last left off", "last left off with", "left off with the", "off with the saturated", "with the saturated fatty", "the saturated fatty acid", "saturated fatty acid decanoyl", "fatty acid decanoyl coa", "acid decanoyl coa and", "decanoyl coa and produces", "coa and produces octanoyl", "and produces octanoyl coa.", "produces octanoyl coa. four", "octanoyl coa. four enzymatic", "coa. four enzymatic 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activity", "thiolase activity present", "activity present in", "present in the mitochondrial", "in the mitochondrial membrane", "the mitochondrial membrane associated", "mitochondrial membrane associated trifunctional", "membrane associated trifunctional protein.", "associated trifunctional protein. note", "trifunctional protein. note that", "protein. note that the", "note that the 3", "that the 3 hydroxyacyl", "dehydrogenase activity of schad", "activity of schad is", "of schad is not", "schad is not actually", "is not actually limited", "not actually limited to", "actually limited to short", "limited to short chain", "to short chain fatty", "short chain fatty acids", "fatty acids in", "acids in fact", "in fact schad has", "fact schad has a", "schad has a broad", "has a broad substrate", "a broad substrate specificity.", "the fourth pass through the", "fourth pass through the beta", "pass through the beta oxidation", "through the beta oxidation spiral", "the beta oxidation spiral picks", "beta oxidation spiral picks up", "oxidation spiral picks up where", "spiral picks up where the", "picks up where the last", "up where the last left", "where the last left off", "the last left off with", "last left off with the", "left off with the saturated", "off with the saturated fatty", "with the saturated fatty acid", "the saturated fatty acid decanoyl", "saturated fatty acid decanoyl coa", "fatty acid decanoyl coa and", "acid decanoyl coa and produces", "decanoyl coa and produces octanoyl", "coa and produces octanoyl coa.", "and produces octanoyl coa. four", "produces octanoyl coa. four enzymatic", "octanoyl coa. four enzymatic steps", "coa. four enzymatic steps are", "four enzymatic steps are required", "enzymatic steps are required starting", "steps are required starting with", "are required starting with mcad", "required starting with mcad coa", "starting with mcad coa dehydrogenase", "mcad coa dehydrogenase medium", "coa dehydrogenase medium chain", "chain activity followed", "activity followed by the", "followed by the enoyl coa", "by the enoyl coa hydratase", "the enoyl coa hydratase activity", "enoyl coa hydratase activity of", "coa hydratase activity of crotonase", "activity of crotonase the", "of crotonase the 3", "crotonase the 3 hydroxyacyl", "the 3 hydroxyacyl coa dehydrogenase", "3 hydroxyacyl coa dehydrogenase activity", "hydroxyacyl coa dehydrogenase activity of", "coa dehydrogenase activity of the", "dehydrogenase activity of the short", "activity of the short chain", "of the short chain 3", "the short chain 3 hydroxyacyl", "short chain 3 hydroxyacyl coa", "chain 3 hydroxyacyl coa dehydrogenase", "hydroxyacyl coa dehydrogenase schad", "schad and completed", "and completed by the ketoacyl", "completed by the ketoacyl coa", "by the ketoacyl coa thiolase", "the ketoacyl coa thiolase activity", "coa thiolase activity present", "thiolase activity present in", "activity present in the", "present in the mitochondrial membrane", "in the mitochondrial membrane associated", "the mitochondrial membrane associated trifunctional", "mitochondrial membrane associated trifunctional protein.", "membrane associated trifunctional protein. note", "associated trifunctional protein. note that", "trifunctional protein. note that the", "protein. note that the 3", "note that the 3 hydroxyacyl", "that the 3 hydroxyacyl coa", "coa dehydrogenase activity of schad", "dehydrogenase activity of schad is", "activity of schad is not", "of schad is not actually", "schad is not actually limited", "is not actually limited to", "not actually limited to short", "actually limited to short chain", "limited to short chain fatty", "to short chain fatty acids", "chain fatty acids in", "fatty acids in fact", "acids in fact schad", "in fact schad has a", "fact schad has a broad", "schad has a broad substrate", "has a broad substrate specificity." ] }, { "record_id": "GLY_000594_1_1482", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77348", "r hsa", "hsa 77348", "r hsa 77348" ] }, { "record_id": "GLY_000594_1_1482", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of octanoyl", "octanoyl coa", "coa to", "to hexanoyl", "hexanoyl coa", "beta oxidation of", "oxidation of octanoyl", "of octanoyl coa", "octanoyl coa to", "coa to hexanoyl", "to hexanoyl coa", "beta oxidation of octanoyl", "oxidation of octanoyl coa", "of octanoyl coa to", "octanoyl coa to hexanoyl", "coa to hexanoyl coa", "beta oxidation of octanoyl coa", "oxidation of octanoyl coa to", "of octanoyl coa to hexanoyl", "octanoyl coa to hexanoyl coa", "the fifth", "fifth pass", "pass through", "through the", "the beta", "oxidation spiral", "spiral picks", "picks up", "up where", "where the", "the last", "last left", "left off", "off with", "with the", "the saturated", "saturated fatty", "fatty acid", "acid octanoyl", "coa and", "and produces", 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"with the saturated", "the saturated fatty", "saturated fatty acid", "fatty acid octanoyl", "acid octanoyl coa", "octanoyl coa and", "coa and produces", "and produces hexanoyl", "produces hexanoyl coa.", "hexanoyl coa. four", "coa. four enzymatic", "four enzymatic steps", "enzymatic steps are", "steps are required", "are required starting", "required starting with", "starting with mcad", "with mcad coa", "mcad coa dehydrogenase", "dehydrogenase medium", "chain activity", "activity followed", "followed by the", "by the enoyl", "the enoyl coa", "enoyl coa hydratase", "coa hydratase activity", "hydratase activity of", "activity of crotonase", "crotonase the", "the 3 hydroxyacyl", "3 hydroxyacyl coa", "hydroxyacyl coa dehydrogenase", "coa dehydrogenase activity", "dehydrogenase activity of", "activity of the", "of the short", "the short chain", "short chain 3", "chain 3 hydroxyacyl", "dehydrogenase schad", "and completed by", "completed by the", "by the ketoacyl", "the ketoacyl coa", "ketoacyl coa thiolase", "coa thiolase activity", "activity present", "present in the", "in the mitochondrial", "the mitochondrial membrane", "mitochondrial membrane associated", "membrane associated trifunctional", "associated trifunctional protein.", "the fifth pass through", "fifth pass through the", "pass through the beta", "through the beta oxidation", "the beta oxidation spiral", "beta oxidation spiral picks", "oxidation spiral picks up", "spiral picks up where", "picks up where the", "up where the last", "where the last left", "the last left off", "last left off with", "left off with the", "off with the saturated", "with the saturated fatty", "the saturated fatty acid", "saturated fatty acid octanoyl", "fatty acid octanoyl coa", "acid octanoyl coa and", "octanoyl coa and produces", "coa and produces hexanoyl", "and produces hexanoyl coa.", "produces hexanoyl coa. four", "hexanoyl coa. four enzymatic", "coa. four enzymatic steps", "four enzymatic steps are", "enzymatic steps are required", "steps are required starting", "are required starting with", "required starting with mcad", "starting with mcad coa", "with mcad coa dehydrogenase", "coa dehydrogenase medium", "dehydrogenase medium chain", "medium chain activity", "activity followed by", "followed by the enoyl", "by the enoyl coa", "the enoyl coa hydratase", "enoyl coa hydratase activity", "coa hydratase activity of", "hydratase activity of crotonase", "of crotonase the", "crotonase the 3", "the 3 hydroxyacyl coa", "3 hydroxyacyl coa dehydrogenase", "hydroxyacyl coa dehydrogenase activity", "coa dehydrogenase activity of", "dehydrogenase activity of the", "activity of the short", "of the short chain", "the short chain 3", "short chain 3 hydroxyacyl", "chain 3 hydroxyacyl coa", "coa dehydrogenase schad", "schad and", "and completed by the", "completed by the ketoacyl", "by the ketoacyl coa", "the ketoacyl coa thiolase", "ketoacyl coa thiolase activity", "thiolase activity present", "activity present in", "present in the mitochondrial", "in the mitochondrial membrane", "the mitochondrial membrane associated", "mitochondrial membrane associated trifunctional", "membrane associated trifunctional protein.", "the fifth pass through the", "fifth pass through the beta", "pass through the beta oxidation", "through the beta oxidation spiral", "the beta oxidation spiral picks", "beta oxidation spiral picks up", "oxidation spiral picks up where", "spiral picks up where the", "picks up where the last", "up where the last left", "where the last left off", "the last left off with", "last left off with the", "left off with the saturated", "off with the saturated fatty", "with the saturated fatty acid", "the saturated fatty acid octanoyl", "saturated fatty acid octanoyl coa", "fatty acid octanoyl coa and", "acid octanoyl coa and produces", "octanoyl coa and produces hexanoyl", "coa and produces hexanoyl coa.", "and produces hexanoyl coa. four", "produces hexanoyl coa. four enzymatic", "hexanoyl coa. 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coa dehydrogenase", "hydroxyacyl coa dehydrogenase schad", "schad and completed", "and completed by the ketoacyl", "completed by the ketoacyl coa", "by the ketoacyl coa thiolase", "the ketoacyl coa thiolase activity", "coa thiolase activity present", "thiolase activity present in", "activity present in the", "present in the mitochondrial membrane", "in the mitochondrial membrane associated", "the mitochondrial membrane associated trifunctional", "mitochondrial membrane associated trifunctional protein." ] }, { "record_id": "GLY_000594_1_1483", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77350", "r hsa", "hsa 77350", "r hsa 77350" ] }, { "record_id": "GLY_000594_1_1483", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of hexanoyl", "hexanoyl coa", "coa to", "to butanoyl", "butanoyl coa", "beta oxidation of", "oxidation of hexanoyl", "of hexanoyl coa", "hexanoyl coa to", "coa to butanoyl", "to butanoyl coa", "beta oxidation of hexanoyl", "oxidation of hexanoyl coa", "of hexanoyl coa to", "hexanoyl coa to butanoyl", "coa to butanoyl coa", "beta oxidation of hexanoyl coa", "oxidation of hexanoyl coa to", "of hexanoyl coa to butanoyl", "hexanoyl coa to butanoyl coa", "the sixth", "sixth pass", "pass through", "through the", "the beta", "oxidation spiral", "spiral picks", "picks up", "up where", "where the", "the last", "last left", "left off", "off with", "with the", "the saturated", "saturated fatty", "fatty acid", "acid hexanoyl", "coa and", "and produces", "produces butanoyl", "butanoyl coa.", "coa. four", "four enzymatic", "enzymatic steps", "steps are", "are required", "required starting", "starting with", "with scad", "scad coa", "coa dehydrogenase", "short chain", "followed by", "by the", "the enoyl", "enoyl coa", "coa hydratase", "hydratase activity", "activity of", "of crotonase", "the 3", "3 hydroxyacyl", "hydroxyacyl coa", 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oxidation spiral picks", "oxidation spiral picks up", "spiral picks up where", "picks up where the", "up where the last", "where the last left", "the last left off", "last left off with", "left off with the", "off with the saturated", "with the saturated fatty", "the saturated fatty acid", "saturated fatty acid hexanoyl", "fatty acid hexanoyl coa", "acid hexanoyl coa and", "hexanoyl coa and produces", "coa and produces butanoyl", "and produces butanoyl coa.", "produces butanoyl coa. four", "butanoyl coa. four enzymatic", "coa. four enzymatic steps", "four enzymatic steps are", "enzymatic steps are required", "steps are required starting", "are required starting with", "required starting with scad", "starting with scad coa", "with scad coa dehydrogenase", "coa dehydrogenase short", "dehydrogenase short chain", "short chain activity", "activity followed by", "followed by the enoyl", "by the enoyl coa", "the enoyl coa hydratase", "enoyl coa hydratase activity", "coa hydratase activity 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the", "followed by the enoyl coa", "by the enoyl coa hydratase", "the enoyl coa hydratase activity", "enoyl coa hydratase activity of", "coa hydratase activity of crotonase", "activity of crotonase the", "of crotonase the 3", "crotonase the 3 hydroxyacyl", "the 3 hydroxyacyl coa dehydrogenase", "3 hydroxyacyl coa dehydrogenase activity", "hydroxyacyl coa dehydrogenase activity of", "coa dehydrogenase activity of the", "dehydrogenase activity of the short", "activity of the short chain", "of the short chain 3", "the short chain 3 hydroxyacyl", "short chain 3 hydroxyacyl coa", "chain 3 hydroxyacyl coa dehydrogenase", "hydroxyacyl coa dehydrogenase schad", "schad and completed", "and completed by the ketoacyl", "completed by the ketoacyl coa", "by the ketoacyl coa thiolase", "the ketoacyl coa thiolase activity", "coa thiolase activity present", "thiolase activity present in", "activity present in the", "present in the mitochondrial membrane", "in the mitochondrial membrane associated", "the mitochondrial membrane associated trifunctional", "mitochondrial membrane associated trifunctional protein." ] }, { "record_id": "GLY_000594_1_1484", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77352", "r hsa", "hsa 77352", "r hsa 77352" ] }, { "record_id": "GLY_000594_1_1484", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of butanoyl", "butanoyl coa", "coa to", "to acetyl", "acetyl coa", "beta oxidation of", "oxidation of butanoyl", "of butanoyl coa", "butanoyl coa to", "coa to acetyl", "to acetyl coa", "beta oxidation of butanoyl", "oxidation of butanoyl coa", "of butanoyl coa to", "butanoyl coa to acetyl", "coa to acetyl coa", "beta oxidation of butanoyl coa", "oxidation of butanoyl coa to", "of butanoyl coa to acetyl", "butanoyl coa to acetyl coa", "the seventh", "seventh and", "and final", "final pass", "pass through", "through the", "the beta", 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beta", "pass through the beta oxidation", "through the beta oxidation spiral", "the beta oxidation spiral picks", "beta oxidation spiral picks up", "oxidation spiral picks up where", "spiral picks up where the", "picks up where the last", "up where the last left", "where the last left off", "the last left off with", "last left off with the", "left off with the saturated", "off with the saturated fatty", "with the saturated fatty acid", "the saturated fatty acid butanoyl", "saturated fatty acid butanoyl coa", "fatty acid butanoyl coa and", "acid butanoyl coa and at", "butanoyl coa and at the", "coa and at the third", "and at the third step", "at the third step produces", "the third step produces acetoacetyl", "third step produces acetoacetyl coa", "produces acetoacetyl coa which", "acetoacetyl coa which can", "coa which can be", "which can be used to", "can be used to generate", "be used to generate 2", "used to generate 2 acetyl", "to generate 2 acetyl coa", "generate 2 acetyl coa 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activity of crotonase", "activity of crotonase the", "of crotonase the 3", "crotonase the 3 hydroxyacyl", "the 3 hydroxyacyl coa dehydrogenase", "3 hydroxyacyl coa dehydrogenase activity", "hydroxyacyl coa dehydrogenase activity of", "coa dehydrogenase activity of the", "dehydrogenase activity of the short", "activity of the short chain", "of the short chain 3", "the short chain 3 hydroxyacyl", "short chain 3 hydroxyacyl coa", "chain 3 hydroxyacyl coa dehydrogenase", "hydroxyacyl coa dehydrogenase schad", "coa dehydrogenase schad .", "dehydrogenase schad . the", "schad . the final enzymatic", ". the final enzymatic step", "final enzymatic step creating", "enzymatic step creating two", "step creating two acetyl", "creating two acetyl coa molecules", "two acetyl coa molecules requires", "acetyl coa molecules requires a", "coa molecules requires a specific", "molecules requires a specific ketoacyl", "requires a specific ketoacyl coa", "a specific ketoacyl coa thiolase", "ketoacyl coa thiolase acetoacetyl", "coa thiolase acetoacetyl coa", "thiolase acetoacetyl coa thiolase." ] }, { "record_id": "GLY_000594_1_1485", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77588", "r hsa", "hsa 77588", "r hsa 77588" ] }, { "record_id": "GLY_000594_1_1485", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "slbp dependent", "dependent processing", "processing of", "of replication", "replication dependent", "dependent histone", "histone pre", "pre mrnas", "slbp dependent processing", "dependent processing of", "processing of replication", "of replication dependent", "replication dependent histone", "dependent histone pre", "histone pre mrnas", "slbp dependent processing of", "dependent processing of replication", "processing of replication dependent", "of replication dependent histone", "replication dependent histone pre", "dependent histone pre mrnas", "slbp dependent processing of 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              1", "are:

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              the", "

              the u7", "u7 snrnp.", "this particle", "particle contains", "contains the", "the u7", "u7 snrna", "the smallest", "smallest of", "of the", "the snrnas", "snrnas which", "which varies", "varies from", "from 57", "57 70", "70 nts", "nts long", "long depending", "depending on", "on the", "the species.", "species. the", "the 5'", "5' end", "end of", "of u7", "snrna binds", "to a", "a sequence", "sequence 3'", "3' of", "the stemloop", "termed the", "histone downstream", "downstream element", "hde .", "are a", "a number", "number of", "of proteins", "proteins found", "found in", "in the", "are 7", "7 sm", "sm proteins", "as are", "are present", "present in", "the spliceosomal", "spliceosomal snrnp.", "five of", "of these", "these proteins", "proteins are", "are the", "the same", "same as", "as ones", "ones found", "spliceosomal snrnps", "snrnps and", "and there", "are 2", "lsm10 and", "and lsm11", "lsm11 that", "that are", "are unique", "unique to", "to u7", "u7 snrnp.

              ", "snrnp.

              a", "a third", "third protein", "protein joins", "joins the", "u7 snrnp", "a large", "large zinc", "zinc finger", "finger protein.", "zfp100 interacts", "interacts with", "with slbp", "slbp bound", "bound to", "mrna and", "and with", "with lsm11", "lsm11 and", "and likely", "likely plays", "plays a", "a critical", "critical role", "role in", "in recruiting", "recruiting u7", "snrnp to", "pre mrna.

              ", "mrna.

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              1 stem", "are:

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              the", "transcribed.

              the u7", "

              the u7 snrnp.", "snrnp. this", "this particle contains", "particle contains the", "contains the u7", "the u7 snrna", "snrna the", "the smallest of", "smallest of the", "of the snrnas", "the snrnas which", "snrnas which varies", "which varies from", "varies from 57", "from 57 70", "57 70 nts", "70 nts long", "nts long depending", "long depending on", "depending on the", "on the species.", "the species. the", "species. the 5'", "the 5' end", "5' end of", "end of u7", "of u7 snrna", "u7 snrna binds", "snrna binds to", "binds to a", "to a sequence", "a sequence 3'", "sequence 3' of", "3' of the", "of the stemloop", "stemloop termed", "termed the histone", "the histone downstream", "histone downstream element", "element hde", ". there", "there are a", "are a number", "a number of", "number of proteins", "of proteins found", "proteins found in", "found in the", "in the u7", "the u7 snrnp.", "snrnp. there", "there are 7", "are 7 sm", "7 sm proteins", "proteins as", "as are present", "are present in", "present in the", "in the spliceosomal", "the spliceosomal snrnp.", "snrnp. five", "five of these", "of these proteins", "these proteins are", "proteins are the", "are the same", "the same as", "same as ones", "as ones found", "ones found in", "the spliceosomal snrnps", "spliceosomal snrnps and", "snrnps and there", "and there are", "there are 2", "2 lsm10", "lsm10 and lsm11", "and lsm11 that", "lsm11 that are", "that are unique", "are unique to", "unique to u7", "to u7 snrnp.

              ", "u7 snrnp.

              a", "snrnp.

              a third", "a third protein", "third protein joins", "protein joins the", "joins the u7", "the u7 snrnp", "snrnp zfp100", "zfp100 a", "a large zinc", "large zinc finger", "zinc finger protein.", "protein. zfp100", "zfp100 interacts with", "interacts with slbp", "with slbp bound", "slbp bound to", "bound to the", "pre mrna and", "mrna and with", "and with lsm11", "with lsm11 and", "lsm11 and likely", "and likely plays", "likely plays a", "plays a critical", "a critical role", "critical role in", "role in recruiting", "in recruiting u7", "recruiting u7 snrnp", "u7 snrnp to", "snrnp to the", "histone pre mrna.

              ", "pre mrna.

              it", "mrna.

              it should", "it should be", "should be noted", "be noted that", "noted that there", "that there must", "there must be", "must be other", "be other trans", "other trans acting", "factors including", "including the factor", "the factor that", "factor that catalyzes", "that catalyzes the", "catalyzes the cleavage", "the cleavage reaction.", "cleavage reaction. the", "reaction. the cleavage", "the cleavage occurs", "cleavage occurs in", "occurs in the", "in the presence", "the presence of", "presence of edta", "of edta as", "edta as does", "as does the", "does the cleavage", "the cleavage reaction", "cleavage reaction in", "reaction in polyadenylation", "polyadenylation it", "it is likely", "is likely that", "likely that this", "that this reaction", "this reaction is", "reaction is catalyzed", "is catalyzed by", "catalyzed by a", "by a protein.", "protein. there", "there may well", "may well be", "well be additional", "be additional proteins", "additional proteins associated", "proteins associated with", "associated with u7", "with u7 snrnp", "and since under", "since under some", "under some conditions", "some conditions in", "conditions in vitro", "in vitro processing", "vitro processing occurs", "processing occurs in", "in the absence", "the absence of", "absence of slbp", "slbp it", "it is possible", "is possible that", "possible that all", "that all of", "all of the", "of the other", "the other factors", "other factors required", "required for processing", "for processing are", "processing are associated", "are associated with", "associated with the", "with the active", "the active form", "active form of", "form of u7", "of u7 snrnp.", "there are two well", "are two well documented", "two well documented trans", "well documented trans acting", "documented trans acting factors", "trans acting factors required", "acting factors required for", "factors required for histone", "required for histone pre", "for histone pre mrna", "histone pre mrna processing.", "mrna processing. these", "processing. these are:

              1", "these are:

              1 stem loop", "are:

              1 stem loop binding", "stem loop binding protein", "binding protein slbp", "slbp also", "also termed hairpin binding", "termed hairpin binding protein", "binding protein hbp", "protein hbp .", "hbp . this", ". this 32", "this 32 kda protein", "32 kda protein is", "kda protein is likely", "protein is likely the", "is likely the first", "likely the first protein", "the first protein that", "first protein that binds", "protein that binds to", "that binds to the", "binds to the histone", "to the histone pre", "the histone pre mrna", "histone pre mrna as", "pre mrna as it", "mrna as it is", "as it is being", "it is being transcribed.", "is being transcribed.

              the", "being transcribed.

              the u7", "transcribed.

              the u7 snrnp.", "u7 snrnp. this", "snrnp. this particle", "this particle contains the", "particle contains the u7", "contains the u7 snrna", "u7 snrna the", "snrna the smallest", "the smallest of the", "smallest of the snrnas", "of the snrnas which", "the snrnas which varies", "snrnas which varies from", "which varies from 57", "varies from 57 70", "from 57 70 nts", "57 70 nts long", "70 nts long depending", "nts long depending on", "long depending on the", "depending on the species.", "on the species. the", "the species. the 5'", "species. the 5' end", "the 5' end of", "5' end of u7", "end of u7 snrna", "of u7 snrna binds", "u7 snrna binds to", "snrna binds to a", "binds to a sequence", "to a sequence 3'", "a sequence 3' of", "sequence 3' of the", "3' of the stemloop", "the stemloop termed", "stemloop termed the", "termed the histone downstream", "the histone downstream element", "downstream element hde", "element hde .", "hde . there", ". there are", "there are a number", "are a number of", "a number of proteins", "number of proteins found", "of proteins found in", "proteins found in the", "found in the u7", "in the u7 snrnp.", "u7 snrnp. there", "snrnp. there are", "there are 7 sm", "are 7 sm proteins", "sm proteins as", "proteins as are", "as are present in", "are present in the", "present in the spliceosomal", "in the spliceosomal snrnp.", "spliceosomal snrnp. five", "snrnp. five of", "five of these proteins", "of these proteins are", "these proteins are the", "proteins are the same", "are the same as", "the same as ones", "same as ones found", "as ones found in", "ones found in the", "found in the spliceosomal", "in the spliceosomal snrnps", "the spliceosomal snrnps and", "spliceosomal snrnps and there", "snrnps and there are", "and there are 2", "are 2 lsm10", "2 lsm10 and", "lsm10 and lsm11 that", "and lsm11 that are", "lsm11 that are unique", "that are unique to", "are unique to u7", "unique to u7 snrnp.

              ", "to u7 snrnp.

              a", "u7 snrnp.

              a third", "snrnp.

              a third protein", "a third protein joins", "third protein joins the", "protein joins the u7", "joins the u7 snrnp", "u7 snrnp zfp100", "zfp100 a large", "a large zinc finger", "large zinc finger protein.", "finger protein. zfp100", "protein. zfp100 interacts", "zfp100 interacts with slbp", "interacts with slbp bound", "with slbp bound to", "slbp bound to the", "bound to the histone", "histone pre mrna and", "pre mrna and with", "mrna and with lsm11", "and with lsm11 and", "with lsm11 and likely", "lsm11 and likely plays", "and likely plays a", "likely plays a critical", "plays a critical role", "a critical role in", "critical role in recruiting", "role in recruiting u7", "in recruiting u7 snrnp", "recruiting u7 snrnp to", "u7 snrnp to the", "snrnp to the histone", "the histone pre mrna.

              ", "histone pre mrna.

              it", "pre mrna.

              it should", "mrna.

              it should be", "it should be noted", "should be noted that", "be noted that there", "noted that there must", "that there must be", "there must be other", "must be other trans", "be other trans acting", "other trans acting factors", "acting factors including", "factors including the", "including the factor that", "the factor that catalyzes", "factor that catalyzes the", "that catalyzes the cleavage", "catalyzes the cleavage reaction.", "the cleavage reaction. the", "cleavage reaction. the cleavage", "reaction. the cleavage occurs", "the cleavage occurs in", "cleavage occurs in the", "occurs in the presence", "in the presence of", "the presence of edta", "presence of edta as", "of edta as does", "edta as does the", "as does the cleavage", "does the cleavage reaction", "the cleavage reaction in", "cleavage reaction in polyadenylation", "in polyadenylation it", "polyadenylation it is", "it is likely that", "is likely that this", "likely that this reaction", "that this reaction is", "this reaction is catalyzed", "reaction is catalyzed by", "is catalyzed by a", "catalyzed by a protein.", "a protein. there", "protein. there may", "there may well be", "may well be additional", "well be additional proteins", "be additional proteins associated", "additional proteins associated with", "proteins associated with u7", "associated with u7 snrnp", "snrnp and", "and since under some", "since under some conditions", "under some conditions in", "some conditions in vitro", "conditions in vitro processing", "in vitro processing occurs", "vitro processing occurs in", "processing occurs in the", "occurs in the absence", "in the absence of", "the absence of slbp", "of slbp it", "slbp it is", "it is possible that", "is possible that all", "possible that all of", "that all of the", "all of the other", "of the other factors", "the other factors required", "other factors required for", "factors required for processing", "required for processing are", "for processing are associated", "processing are associated with", "are associated with the", "associated with the active", "with the active form", "the active form of", "active form of u7", "form of u7 snrnp.", "there are two well documented", "are two well documented trans", "two well documented trans acting", "well documented trans acting factors", "documented trans acting factors required", "trans acting factors required for", "acting factors required for histone", "factors required for histone pre", "required for histone pre mrna", "for histone pre mrna processing.", "pre mrna processing. these", "mrna processing. these are:

              1", "processing. these are:

              1 stem", "these are:

              1 stem loop binding", "are:

              1 stem loop binding protein", "loop binding protein slbp", "slbp also termed", "also termed hairpin binding protein", "hairpin binding protein hbp", "binding protein hbp .", "hbp . this 32", ". this 32 kda", "this 32 kda protein is", "32 kda protein is likely", "kda protein is likely the", "protein is likely the first", "is likely the first protein", "likely the first protein that", "the first protein that binds", "first protein that binds to", "protein that binds to the", "that binds to the histone", "binds to the histone pre", "to the histone pre mrna", "the histone pre mrna as", "histone pre mrna as it", "pre mrna as it is", "mrna as it is being", "as it is being transcribed.", "it is being transcribed.

              the", "is being transcribed.

              the u7", "being transcribed.

              the u7 snrnp.", "

              the u7 snrnp. this", "u7 snrnp. this particle", "snrnp. this particle contains", "this particle contains the u7", "particle contains the u7 snrna", "the u7 snrna the", "u7 snrna the smallest", "snrna the smallest of", "the smallest of the snrnas", "smallest of the snrnas which", "of the snrnas which varies", "the snrnas which varies from", "snrnas which varies from 57", "which varies from 57 70", "varies from 57 70 nts", "from 57 70 nts long", "57 70 nts long depending", "70 nts long depending on", "nts long depending on the", "long depending on the species.", "depending on the species. the", "on the species. the 5'", "the species. the 5' end", "species. the 5' end of", "the 5' end of u7", "5' end of u7 snrna", "end of u7 snrna binds", "of u7 snrna binds to", "u7 snrna binds to a", "snrna binds to a sequence", "binds to a sequence 3'", "to a sequence 3' of", "a sequence 3' of the", "sequence 3' of the stemloop", "of the stemloop termed", "the stemloop termed the", "stemloop termed the histone", "termed the histone downstream element", "histone downstream element hde", "downstream element hde .", "hde . there are", ". there are a", "there are a number of", "are a number of proteins", "a number of proteins found", "number of proteins found in", "of proteins found in the", "proteins found in the u7", "found in the u7 snrnp.", "the u7 snrnp. there", "u7 snrnp. there are", "snrnp. there are 7", "there are 7 sm proteins", "7 sm proteins as", "sm proteins as are", "proteins as are present", "as are present in the", "are present in the spliceosomal", "present in the spliceosomal snrnp.", "the spliceosomal snrnp. five", "spliceosomal snrnp. five of", "snrnp. five of these", "five of these proteins are", "of these proteins are the", "these proteins are the same", "proteins are the same as", "are the same as ones", "the same as ones found", "same as ones found in", "as ones found in the", "ones found in the spliceosomal", "found in the spliceosomal snrnps", "in the spliceosomal snrnps and", "the spliceosomal snrnps and there", "spliceosomal snrnps and there are", "snrnps and there are 2", "there are 2 lsm10", "are 2 lsm10 and", "2 lsm10 and lsm11", "lsm10 and lsm11 that are", "and lsm11 that are unique", "lsm11 that are unique to", "that are unique to u7", "are unique to u7 snrnp.

              ", "unique to u7 snrnp.

              a", "to u7 snrnp.

              a third", "u7 snrnp.

              a third protein", "snrnp.

              a third protein joins", "a third protein joins the", "third protein joins the u7", "protein joins the u7 snrnp", "the u7 snrnp zfp100", "snrnp zfp100 a", "zfp100 a large zinc", "a large zinc finger protein.", "zinc finger protein. zfp100", "finger protein. zfp100 interacts", "protein. zfp100 interacts with", "zfp100 interacts with slbp bound", "interacts with slbp bound to", "with slbp bound to the", "slbp bound to the histone", "bound to the histone pre", "the histone pre mrna and", "histone pre mrna and with", "pre mrna and with lsm11", "mrna and with lsm11 and", "and with lsm11 and likely", "with lsm11 and likely plays", "lsm11 and likely plays a", "and likely plays a critical", "likely plays a critical role", "plays a critical role in", "a critical role in recruiting", "critical role in recruiting u7", "role in recruiting u7 snrnp", "in recruiting u7 snrnp to", "recruiting u7 snrnp to the", "u7 snrnp to the histone", "snrnp to the histone pre", "to the histone pre mrna.

              ", "the histone pre mrna.

              it", "histone pre mrna.

              it should", "pre mrna.

              it should be", "mrna.

              it should be noted", "it should be noted that", "should be noted that there", "be noted that there must", "noted that there must be", "that there must be other", "there must be other trans", "must be other trans acting", "be other trans acting factors", "trans acting factors including", "acting factors including the", "factors including the factor", "including the factor that catalyzes", "the factor that catalyzes the", "factor that catalyzes the cleavage", "that catalyzes the cleavage reaction.", "catalyzes the cleavage reaction. the", "the cleavage reaction. the cleavage", "cleavage reaction. the cleavage occurs", "reaction. the cleavage occurs in", "the cleavage occurs in the", "cleavage occurs in the presence", "occurs in the presence of", "in the presence of edta", "the presence of edta as", "presence of edta as does", "of edta as does the", "edta as does the cleavage", "as does the cleavage reaction", "does the cleavage reaction in", "the cleavage reaction in polyadenylation", "reaction in polyadenylation it", "in polyadenylation it is", "polyadenylation it is likely", "it is likely that this", "is likely that this reaction", "likely that this reaction is", "that this reaction is catalyzed", "this reaction is catalyzed by", "reaction is catalyzed by a", "is catalyzed by a protein.", "by a protein. there", "a protein. there may", "protein. there may well", "there may well be additional", "may well be additional proteins", "well be additional proteins associated", "be additional proteins associated with", "additional proteins associated with u7", "proteins associated with u7 snrnp", "u7 snrnp and", "snrnp and since", "and since under some conditions", "since under some conditions in", "under some conditions in vitro", "some conditions in vitro processing", "conditions in vitro processing occurs", "in vitro processing occurs in", "vitro processing occurs in the", "processing occurs in the absence", "occurs in the absence of", "in the absence of slbp", "absence of slbp it", "of slbp it is", "slbp it is possible", "it is possible that all", "is possible that all of", "possible that all of the", "that all of the other", "all of the other factors", "of the other factors required", "the other factors required for", "other factors required for processing", "factors required for processing are", "required for processing are associated", "for processing are associated with", "processing are associated with the", "are associated with the active", "associated with the active form", "with the active form of", "the active form of u7", "active form of u7 snrnp." ] }, { "record_id": "GLY_000594_1_1486", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "804914", "r hsa", "hsa 804914", "r hsa 804914" ] }, { "record_id": "GLY_000594_1_1486", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transport of", "of fatty", "fatty acids", "transport of fatty", "of fatty acids", "transport of fatty acids", "long chain", "chain fatty", "are involved", "involved in", "in many", "many cellular", "cellular functions.", "functions. they", "they can", "can be", "be used", "used as", "as an", "an important", "important source", "source of", "of energy", "energy by", "by skeletal", "skeletal muscle", "muscle and", "and heart", "heart tissues.", "tissues. also", "they are", "are used", "used in", "in the", "the production", "production of", "of hormones", "hormones which", "which can", "can regulate", "regulate inflammation", "blood pressure", "the clotting", "clotting process", "blood lipid", "lipid levels", "levels and", "and the", "the immune", "immune response.", "response. fatty", "fatty acid", "acid transporter", "transporter proteins", "are a", "a family", "family of", "of proteins", "proteins which", "which mediate", "mediate fatty", "acid uptake", "uptake into", "into cells", "cells when", "when overexpressed.", "overexpressed. fatps", "fatps also", "also possess", "possess enzymatic", "enzymatic activity", "the details", "details of", "of which", "which are", "are captured", "captured elsewhere.", "elsewhere. there", "there are", "are 6", "6 human", "human genes", "genes of", "of the", "the slc27a", "slc27a family", "family which", "which encode", "encode for", "for fatp1", "fatp1 6", "stahl a", "gimeno re", "2007 .", ". to", "to date", "only fatp1", "4 and", "and 6", "6 have", "have demonstrable", "demonstrable transporter", "transporter function.", "function. fatty", "acids with", "with carbon", "carbon chain", "chain lengths", "lengths of", "of more", "more than", "than 10", "10 are", "are the", "the most", "most likely", "likely substrates", "substrates for", "for these", "these transporters.", "long chain fatty", "chain fatty acids", "acids lcfas", "lcfas are", "are involved in", "involved in many", "in many cellular", "many cellular functions.", "cellular functions. they", "functions. they can", "they can be", "can be used", "be used as", "used as an", "as an important", "an important source", "important source of", "source of energy", "of energy by", "energy by skeletal", "by skeletal muscle", "skeletal muscle and", "muscle and heart", "and heart tissues.", "heart tissues. also", "also they", "they are used", "are used in", "used in the", "in the production", "the production of", "production of hormones", "of hormones which", "hormones which can", "which can regulate", "can regulate inflammation", "inflammation blood", "pressure the", "the clotting process", "process blood", "blood lipid levels", "lipid levels and", "levels and the", "and the immune", "the immune response.", "immune response. fatty", "response. fatty acid", "fatty acid transporter", "acid transporter proteins", "proteins fatps", "fatps are", "are a family", "a family of", "family of proteins", "of proteins which", "proteins which mediate", "which mediate fatty", "mediate fatty acid", "fatty acid uptake", "acid uptake into", "uptake into cells", "into cells when", "cells when overexpressed.", "when overexpressed. fatps", "overexpressed. fatps also", "fatps also possess", "also possess enzymatic", "possess enzymatic activity", "activity the", "the details of", "details of which", "of which are", "which are captured", "are captured elsewhere.", "captured elsewhere. there", "elsewhere. there are", "there are 6", "are 6 human", "6 human genes", "human genes of", "genes of the", "of the slc27a", "the slc27a family", "slc27a family which", "family which encode", "which encode for", "encode for fatp1", "for fatp1 6", "6 stahl", "a 2004", "2004 gimeno", "re 2007", "2007 . to", ". to date", "date only", "fatp1 4", "4 and 6", "and 6 have", "6 have demonstrable", "have demonstrable transporter", "demonstrable transporter function.", "transporter function. fatty", "function. fatty acids", "fatty acids with", "acids with carbon", "with carbon chain", "carbon chain lengths", "chain lengths of", "lengths of more", "of more than", "more than 10", "than 10 are", "10 are the", "are the most", "the most likely", "most likely substrates", "likely substrates for", "substrates for these", "for these transporters.", "long chain fatty acids", "fatty acids lcfas", "lcfas are involved", "are involved in many", "involved in many cellular", "in many cellular functions.", "many cellular functions. they", "cellular functions. they can", "functions. they can be", "they can be used", "can be used as", "be used as an", "used as an important", "as an important source", "an important source of", "important source of energy", "source of energy by", "of energy by skeletal", "energy by skeletal muscle", "by skeletal muscle and", "skeletal muscle and heart", "muscle and heart tissues.", "and heart tissues. also", "tissues. also they", "also they are", "they are used in", "are used in the", "used in the production", "in the production of", "the production of hormones", "production of hormones which", "of hormones which can", "hormones which can regulate", "which can regulate inflammation", "regulate inflammation blood", "inflammation blood pressure", "blood pressure the", "pressure the clotting", "clotting process blood", "process blood lipid", "blood lipid levels and", "lipid levels and the", "levels and the immune", "and the immune response.", "the immune response. fatty", "immune response. fatty acid", "response. fatty acid transporter", "fatty acid transporter proteins", "transporter proteins fatps", "fatps are a", "are a family of", "a family of proteins", "family of proteins which", "of proteins which mediate", "proteins which mediate fatty", "which mediate fatty acid", "mediate fatty acid uptake", "fatty acid uptake into", "acid uptake into cells", "uptake into cells when", "into cells when overexpressed.", "cells when overexpressed. fatps", "when overexpressed. fatps also", "overexpressed. fatps also possess", "fatps also possess enzymatic", "also possess enzymatic activity", "enzymatic activity the", "activity the details", "the details of which", "details of which are", "of which are captured", "which are captured elsewhere.", "are captured elsewhere. there", "captured elsewhere. there are", "elsewhere. there are 6", "there are 6 human", "are 6 human genes", "6 human genes of", "human genes of the", "genes of the slc27a", "of the slc27a family", "the slc27a family which", "slc27a family which encode", "family which encode for", "which encode for fatp1", "encode for fatp1 6", "fatp1 6 stahl", "6 stahl a", "stahl a 2004", "2004 gimeno re", "gimeno re 2007", "re 2007 .", "2007 . to date", "to date only", "date only fatp1", "only fatp1 4", "fatp1 4 and", "4 and 6 have", "and 6 have demonstrable", "6 have demonstrable transporter", "have demonstrable transporter function.", "demonstrable transporter function. fatty", "transporter function. fatty acids", "function. fatty acids with", "fatty acids with carbon", "acids with carbon chain", "with carbon chain lengths", "carbon chain lengths of", "chain lengths of more", "lengths of more than", "of more than 10", "more than 10 are", "than 10 are the", "10 are the most", "are the most likely", "the most likely substrates", "most likely substrates for", "likely substrates for these", "substrates for these transporters.", "chain fatty acids lcfas", "acids lcfas are", "lcfas are involved in", "are involved in many cellular", "involved in many cellular functions.", "in many cellular functions. they", "many cellular functions. they can", "cellular functions. they can be", "functions. they can be used", "they can be used as", "can be used as an", "be used as an important", "used as an important source", "as an important source of", "an important source of energy", "important source of energy by", "source of energy by skeletal", "of energy by skeletal muscle", "energy by skeletal muscle and", "by skeletal muscle and heart", "skeletal muscle and heart tissues.", "muscle and heart tissues. also", "heart tissues. also they", "tissues. also they are", "also they are used", "they are used in the", "are used in the production", "used in the production of", "in the production of hormones", "the production of hormones which", "production of hormones which can", "of hormones which can regulate", "hormones which can regulate inflammation", "can regulate inflammation blood", "regulate inflammation blood pressure", "blood pressure the clotting", "pressure the clotting process", "the clotting process blood", "clotting process blood lipid", "process blood lipid levels", "blood lipid levels and the", "lipid levels and the immune", "levels and the immune response.", "and the immune response. fatty", "the immune response. fatty acid", "immune response. fatty acid transporter", "response. fatty acid transporter proteins", "acid transporter proteins fatps", "proteins fatps are", "fatps are a family", "are a family of proteins", "a family of proteins which", "family of proteins which mediate", "of proteins which mediate fatty", "proteins which mediate fatty acid", "which mediate fatty acid uptake", "mediate fatty acid uptake into", "fatty acid uptake into cells", "acid uptake into cells when", "uptake into cells when overexpressed.", "into cells when overexpressed. fatps", "cells when overexpressed. fatps also", "when overexpressed. fatps also possess", "overexpressed. fatps also possess enzymatic", "fatps also possess enzymatic activity", "possess enzymatic activity the", "enzymatic activity the details", "activity the details of", "the details of which are", "details of which are captured", "of which are captured elsewhere.", "which are captured elsewhere. there", "are captured elsewhere. there are", "captured elsewhere. there are 6", "elsewhere. there are 6 human", "there are 6 human genes", "are 6 human genes of", "6 human genes of the", "human genes of the slc27a", "genes of the slc27a family", "of the slc27a family which", "the slc27a family which encode", "slc27a family which encode for", "family which encode for fatp1", "which encode for fatp1 6", "for fatp1 6 stahl", "fatp1 6 stahl a", "a 2004 gimeno", "gimeno re 2007 .", "re 2007 . to", ". to date only", "to date only fatp1", "only fatp1 4 and", "fatp1 4 and 6", "4 and 6 have demonstrable", "and 6 have demonstrable transporter", "6 have demonstrable transporter function.", "have demonstrable transporter function. fatty", "demonstrable transporter function. fatty acids", "transporter function. fatty acids with", "function. fatty acids with carbon", "fatty acids with carbon chain", "acids with carbon chain lengths", "with carbon chain lengths of", "carbon chain lengths of more", "chain lengths of more than", "lengths of more than 10", "of more than 10 are", "more than 10 are the", "than 10 are the most", "10 are the most likely", "are the most likely substrates", "the most likely substrates for", "most likely substrates for these", "likely substrates for these transporters." ] }, { "record_id": 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"c terminal extension", "terminal extension containing", "extension containing a", "containing a card", "a card domain", "domain which", "which has been", "has been reported", "been reported to", "reported to interact", "to interact directly", "interact directly with", "directly with procaspase", "with procaspase 1", "1 obviating", "obviating a requirement", "a requirement for", "requirement for asc", "asc faustin", "though asc was", "asc was found", "was found to", "found to augment", "to augment the", "augment the interaction.", "the interaction. mouse", "interaction. mouse nlrp1", "mouse nlrp1 has", "nlrp1 has no", "has no pyd", "no pyd domain", "pyd domain and", "domain and would", "and would therefore", "would therefore not", "therefore not be", "not be expected", "be expected to", "expected to interact", "with procaspase 1.", "procaspase 1. like", "1. like the", "like the nlrp3", "the nlrp3 inflammasome", "inflammasome k+", "k+ efflux appears", "efflux appears to", "appears to be", "to be essential", "be essential for", "essential for caspase", "for caspase 1", "caspase 1 activation", "activation wickliffe", "wickliffe et al.", "et al. 2008", "al. 2008 .", "2008 . ribonucleoside", ". ribonucleoside triphosphates", "triphosphates ntps", "ntps are", "are required for", "required for nalp1", "for nalp1 mediated", "nalp1 mediated caspase", "mediated caspase 1", "1 activation with", "activation with atp", "with atp being", "atp being the", "being the most", "the most efficient", "efficient mg2+", "mg2+ was also", "was also required", "required faustin", ". the human", "the human nlrp1", "human nlrp1 gene", "nlrp1 gene has", "gene has 3", "has 3 paralogues", "3 paralogues in", "paralogues in mouse", "in mouse that", "mouse that are", "that are highly", "are highly polymorphic.", "highly polymorphic. differences", "polymorphic. differences between", "differences between mouse", "between mouse strains", "mouse strains underlie", "strains underlie susceptibility", 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efficient", "most efficient mg2+", "efficient mg2+ was", "mg2+ was also required", "also required faustin", "required faustin et", "2007 . the human", ". the human nlrp1", "the human nlrp1 gene", "human nlrp1 gene has", "nlrp1 gene has 3", "gene has 3 paralogues", "has 3 paralogues in", "3 paralogues in mouse", "paralogues in mouse that", "in mouse that are", "mouse that are highly", "that are highly polymorphic.", "are highly polymorphic. differences", "highly polymorphic. differences between", "polymorphic. differences between mouse", "differences between mouse strains", "between mouse strains underlie", "mouse strains underlie susceptibility", "strains underlie susceptibility to", "underlie susceptibility to anthrax", "susceptibility to anthrax lethal", "to anthrax lethal toxin", "lethal toxin boyden", "toxin boyden &", "boyden & dietrich 2006", "& dietrich 2006 .", "nlrp1 is activated by mdp", "activated by mdp faustin", "by mdp faustin et", "mdp faustin et al.", "faustin et al. 2007 .", "et al. 2007 . the", "al. 2007 . the nlrp1", "2007 . the nlrp1 inflammasome", ". the nlrp1 inflammasome was", "the nlrp1 inflammasome was the", "nlrp1 inflammasome was the first", "inflammasome was the first to", "was the first to be", "the first to be characterized.", "first to be characterized. it", "to be characterized. it was", "be characterized. it was described", "characterized. it was described as", "it was described as a", "was described as a complex", "described as a complex containing", "as a complex containing nalp1", "complex containing nalp1 asc", "nalp1 asc caspase", "asc caspase 1 and", "caspase 1 and caspase 5", "and caspase 5 martinon", "caspase 5 martinon et", "5 martinon et al.", "martinon et al. 2002 .", "et al. 2002 . unlike", "al. 2002 . unlike nlrp3", ". unlike nlrp3 nlrp1", "unlike nlrp3 nlrp1 has", "nlrp3 nlrp1 has a", "nlrp1 has a c terminal", "has a c terminal extension", "a c terminal extension containing", "c terminal extension containing a", 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              the", ".

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              the", "1995 .

              the major", ".

              the major inflammatory", "major inflammatory pathway", "inflammatory pathway stimulated", "pathway stimulated by", "stimulated by ager", "by ager activation", "ager activation is", "activation is nfkappab.", "is nfkappab. though", "nfkappab. though the", "though the signaling", "the signaling cascade", "signaling cascade is", "cascade is unclear", "unclear several", "several pieces of", "pieces of experimental", "of experimental data", "experimental data suggest", "data suggest that", "suggest that activation", "that activation of", "activation of ager", "of ager leads", "ager leads to", "leads to sustained", "to sustained activation", "sustained activation and", "activation and upregulation", "and upregulation of", "upregulation of nfkappab", "nfkappab measured", "measured as nfkappab", "as nfkappab translocation", "nfkappab translocation to", "translocation to the", "to the nucleus", "nucleus and", "and increased levels", "increased levels of", "levels of de", "of de novo", "de novo synthesized", "novo synthesized nfkappab", "nfkappab bierhaus", "bierhaus et al.", "et al. 2001", "al. 2001 .", "2001 . as", ". as this", "as this is", "this is clearly", "is clearly an", "clearly an indirect", "an indirect effect", "indirect effect it", "effect it is", "it is represented", "is represented here", "represented here as", "here as positive", "as positive regulation", "positive regulation of", "regulation of nfkappab", "of nfkappab translocation", "to the nucleus.", "the nucleus. ager", "nucleus. ager can", "ager can bind", "can bind erk1/2", "bind erk1/2 and", "erk1/2 and thereby", "and thereby activate", "thereby activate the", "activate the mapk", "the mapk and", "mapk and jnk", "and jnk cascades", "cascades bierhaus", "et al. 2005", "al. 2005 .", "glycosylation end product", "end product specific", "specific receptor ager", "ager also known", "also known as receptor", "known as receptor for", "as receptor for advanced", "receptor for advanced glycation", "for advanced glycation end", "advanced glycation end products", "end products rage", "rage is a", "is a multi ligand", "a multi ligand membrane", "multi ligand membrane receptor", "ligand membrane receptor belonging", "membrane receptor belonging to", "receptor belonging to the", "belonging to the immunoglobulin", "to the immunoglobulin superfamily.", "the immunoglobulin superfamily. it", "immunoglobulin superfamily. it is", "superfamily. it is considered", "it is considered to", "is considered to be", "considered to be a", "to be a pattern", "be a pattern recognition", "a pattern recognition receptor", "recognition receptor liliensiek", "receptor liliensiek et", "liliensiek et al. 2004", "et al. 2004 .", "al. 2004 . it", "2004 . it recognizes", ". it recognizes a", "it recognizes a large", "recognizes a large variety", "a large variety of", "large variety of modified", "variety of modified proteins", "of modified proteins known", "modified proteins known as", "proteins known as advanced", "known as advanced glycation/glycosylation", "as advanced glycation/glycosylation endproducts", "glycation/glycosylation endproducts ages", "ages a", "a heterogenous group of", "heterogenous group of structures", "group of structures that", "of structures that are", "structures that are generated", "that are generated by", "are generated by the", "generated by the maillard", "by the maillard reaction", "maillard reaction a", "reaction a consequence", "a consequence of long", "consequence of long term", "of long term incubation", "long term incubation of", "term incubation of proteins", "incubation of proteins with", "of proteins with glucose", "with glucose ikeda", "glucose ikeda et", "ikeda et al. 1996", "et al. 1996 .", "al. 1996 . their", "1996 . their accumulation", ". their accumulation is", "their accumulation is associated", "accumulation is associated with", "is associated with diabetes", "with diabetes atherosclerosis", "atherosclerosis renal failure", "renal failure and ageing", "and ageing schmidt", "ageing schmidt et", "schmidt et al. 1999", "et al. 1999 .", "al. 1999 . the", "1999 . the most", ". the most prevalent", "the most prevalent class", "most prevalent class of", "prevalent class of age", "class of age in", "of age in vivo", "age in vivo are", "in vivo are n", "vivo are n 6", "n 6 carboxymethyllysine", "adducts kislinger et", "kislinger et al. 1991", "et al. 1991 .", "al. 1991 . in", "1991 . in addition", ". in addition to", "in addition to ages", "to ages ager", "ages ager is", "ager is a signal", "is a signal transduction", "a signal transduction receptor", "signal transduction receptor for", "transduction receptor for amyloid", "receptor for amyloid beta", "for amyloid beta peptide", "beta peptide ab", "ab yan", "yan et al. 1996", "1996 mediating", "mediating ab neurotoxicity and", "ab neurotoxicity and promoting", "neurotoxicity and promoting ab", "and promoting ab influx", "promoting ab influx into", "ab influx into the", "influx into the brain.", "into the brain. ager", "the brain. ager also", "brain. ager also responds", "ager also responds to", "also responds to the", "responds to the proinflammatory", "to the proinflammatory s100/calgranulins", "proinflammatory s100/calgranulins hofmann", "s100/calgranulins hofmann et", "hofmann et al. 1999", "al. 1999 and", "1999 and high", "and high mobility group", "high mobility group protein", "mobility group protein b1", "protein b1 hmgb1/amphoterin/def", "hmgb1/amphoterin/def a", "a protein linked to", "protein linked to neurite", "linked to neurite outgrowth", "to neurite outgrowth and", "neurite outgrowth and cellular", "outgrowth and cellular motility", "cellular motility hori", "motility hori et", "hori et al. 1995", "et al. 1995 .

              the", "al. 1995 .

              the major", "1995 .

              the major inflammatory", ".

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"measured as nfkappab translocation", "as nfkappab translocation to", "nfkappab translocation to the", "translocation to the nucleus", "the nucleus and", "nucleus and increased", "and increased levels of", "increased levels of de", "levels of de novo", "of de novo synthesized", "de novo synthesized nfkappab", "synthesized nfkappab bierhaus", "nfkappab bierhaus et", "bierhaus et al. 2001", "et al. 2001 .", "al. 2001 . as", "2001 . as this", ". as this is", "as this is clearly", "this is clearly an", "is clearly an indirect", "clearly an indirect effect", "an indirect effect it", "indirect effect it is", "effect it is represented", "it is represented here", "is represented here as", "represented here as positive", "here as positive regulation", "as positive regulation of", "positive regulation of nfkappab", "regulation of nfkappab translocation", "of nfkappab translocation to", "translocation to the nucleus.", "to the nucleus. ager", "the nucleus. ager can", "nucleus. ager can bind", 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endproducts ages", "ages a heterogenous", "a heterogenous group of structures", "heterogenous group of structures that", "group of structures that are", "of structures that are generated", "structures that are generated by", "that are generated by the", "are generated by the maillard", "generated by the maillard reaction", "the maillard reaction a", "maillard reaction a consequence", "reaction a consequence of", "a consequence of long term", "consequence of long term incubation", "of long term incubation of", "long term incubation of proteins", "term incubation of proteins with", "incubation of proteins with glucose", "proteins with glucose ikeda", "with glucose ikeda et", "glucose ikeda et al.", "ikeda et al. 1996 .", "et al. 1996 . their", "al. 1996 . their accumulation", "1996 . their accumulation is", ". their accumulation is associated", "their accumulation is associated with", "accumulation is associated with diabetes", "associated with diabetes atherosclerosis", "diabetes atherosclerosis renal", "atherosclerosis renal failure and", "failure and ageing schmidt", "and ageing schmidt et", "ageing schmidt et al.", "schmidt et al. 1999 .", "et al. 1999 . the", "al. 1999 . the most", "1999 . the most prevalent", ". the most prevalent class", "the most prevalent class of", "most prevalent class of age", "prevalent class of age in", "class of age in vivo", "of age in vivo are", "age in vivo are n", "in vivo are n 6", "are n 6 carboxymethyllysine", "6 carboxymethyllysine necml", "carboxymethyllysine necml adducts", "necml adducts kislinger", "adducts kislinger et al.", "kislinger et al. 1991 .", "et al. 1991 . in", "al. 1991 . in addition", "1991 . in addition to", ". in addition to ages", "addition to ages ager", "to ages ager is", "ages ager is a", "ager is a signal transduction", "is a signal transduction receptor", "a signal transduction receptor for", "signal transduction receptor for amyloid", "transduction receptor for amyloid beta", "receptor for amyloid beta peptide", "amyloid beta peptide ab", "ab yan et", "al. 1996 mediating", "1996 mediating ab", "mediating ab neurotoxicity and promoting", "ab neurotoxicity and promoting ab", "neurotoxicity and promoting ab influx", "and promoting ab influx into", "promoting ab influx into the", "ab influx into the brain.", "influx into the brain. ager", "into the brain. ager also", "the brain. ager also responds", "brain. ager also responds to", "ager also responds to the", "also responds to the proinflammatory", "responds to the proinflammatory s100/calgranulins", "the proinflammatory s100/calgranulins hofmann", "proinflammatory s100/calgranulins hofmann et", "s100/calgranulins hofmann et al.", "et al. 1999 and", "al. 1999 and high", "1999 and high mobility", "and high mobility group protein", "high mobility group protein b1", "group protein b1 hmgb1/amphoterin/def", "hmgb1/amphoterin/def a protein", "a protein linked to neurite", "protein linked to neurite outgrowth", "linked to neurite 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              the", "et al. 1995 .

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              the major inflammatory", "1995 .

              the major inflammatory pathway", ".

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"human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "met activates", "activates stat3", "met activates stat3", "the stat3", "stat3 transcription", "transcription factor", "factor binds", "binds to", "to activated", "activated met", "met through", "through phosphorylated", "phosphorylated tyrosine", "tyrosine residue", "residue y1356", "y1356 of", "of met.", "met. stat3", "stat3 may", "may also", "also bind", "bind to", "met indirectly", "indirectly through", "through gab1", "but this", "this interaction", "interaction has", "has not", "not been", "been studied", "studied in", "in detail.", "detail. activated", "met induces", "induces phosphorylation", "phosphorylation of", "of stat3", "stat3 at", "at y705", "triggering stat3", "stat3 dimerization", "dimerization and", "and nuclear", "nuclear translocation", "schaper et", "et al.", "al. 1997", "boccaccio et", "al. 1998", "zhang et", "al. 2002", "cramer et", "al. 2005", "2005 .", ". endocytosis", "endocytosis of", "of 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"mediated activation of stat3", "activation of stat3 is", "of stat3 is implicated", "stat3 is implicated in", "is implicated in anchorage", "implicated in anchorage independent", "in anchorage independent cell", "anchorage independent cell growth", "independent cell growth and", "cell growth and invasiveness", "growth and invasiveness downstream", "and invasiveness downstream of", "invasiveness downstream of hgf", "of hgf zhang", "hgf zhang et", "al. 2005 . met", "2005 . met can", ". met can also", "met can also interact", "can also interact with", "also interact with stat1a", "with stat1a stat1b", "stat1a stat1b and", "and stat5 but", "stat5 but the", "but the biological importance", "the biological importance of", "biological importance of these", "importance of these interactions", "of these interactions is", "these interactions is not", "interactions is not known", "not known runge", "known runge et", "runge et al. 1999", "et al. 1999 .", "the stat3 transcription factor binds", "stat3 transcription factor binds to", "transcription factor binds to activated", "factor binds to activated met", "binds to activated met through", "to activated met through phosphorylated", "activated met through phosphorylated tyrosine", "met through phosphorylated tyrosine residue", "through phosphorylated tyrosine residue y1356", "phosphorylated tyrosine residue y1356 of", "tyrosine residue y1356 of met.", "residue y1356 of met. stat3", "y1356 of met. stat3 may", "of met. stat3 may also", "met. stat3 may also bind", "stat3 may also bind to", "may also bind to activated", "also bind to activated met", "bind to activated met indirectly", "to activated met indirectly through", "activated met indirectly through gab1", "indirectly through gab1 but", "through gab1 but this", "gab1 but this interaction", "but this interaction has not", "this interaction has not been", "interaction has not been studied", "has not been studied in", "not been studied in detail.", "been studied in detail. activated", "studied in detail. activated met", "in detail. activated met induces", "detail. activated met induces phosphorylation", "activated met induces phosphorylation of", "met induces phosphorylation of stat3", "induces phosphorylation of stat3 at", "phosphorylation of stat3 at y705", "stat3 at y705 triggering", "at y705 triggering stat3", "y705 triggering stat3 dimerization", "triggering stat3 dimerization and nuclear", "stat3 dimerization and nuclear translocation", "and nuclear translocation schaper", "nuclear translocation schaper et", "translocation schaper et al.", "et al. 1997 boccaccio", "al. 1997 boccaccio et", "1997 boccaccio et al.", "et al. 1998 zhang", "al. 1998 zhang et", "1998 zhang et al.", "et al. 2002 cramer", "al. 2002 cramer et", "2002 cramer et al.", "cramer et al. 2005 .", "et al. 2005 . endocytosis", "al. 2005 . endocytosis of", "2005 . endocytosis of met", ". endocytosis of met and", "endocytosis of met and interaction", "of met and interaction with", "met and interaction with stat3", "and interaction with stat3 at", "interaction with stat3 at endosomes", "with stat3 at endosomes may", "stat3 at endosomes may be", "at endosomes may be required", "endosomes may be required for", "may be required for sustained", "be required for sustained stat3", "required for sustained stat3 phosphorylation", "for sustained stat3 phosphorylation in", "sustained stat3 phosphorylation in response", "stat3 phosphorylation in response to", "phosphorylation in response to hgf", "in response to hgf stimulation", "to hgf stimulation kermorgant", "hgf stimulation kermorgant and", "stimulation kermorgant and parker", "kermorgant and parker 2008 .", "and parker 2008 . activated", "parker 2008 . activated src", "2008 . activated src may", ". activated src may also", "activated src may also contribute", "src may also contribute to", "may also contribute to phosphorylation", "also contribute to phosphorylation of", "contribute to phosphorylation of stat3", "to phosphorylation of stat3 at", "phosphorylation of stat3 at y705.", "of stat3 at y705. stat3", "stat3 at y705. stat3 may", "at y705. stat3 may promote", "y705. stat3 may promote hgf", "stat3 may promote hgf transcription", "may promote hgf transcription in", "promote hgf transcription in a", "hgf transcription in a src", "transcription in a src dependent", "in a src dependent way", "src dependent way but", "dependent way but this", "way but this autocrine", "but this autocrine hgf loop", "this autocrine hgf loop may", "autocrine hgf loop may be", "hgf loop may be limited", "loop may be limited to", "may be limited to breast", "be limited to breast cancer", "limited to breast cancer cells", "breast cancer cells wojcik", "cancer cells wojcik et", "cells wojcik et al.", "et al. 2006 sam", "al. 2006 sam et", "2006 sam et al.", "sam et al. 2007 .", "et al. 2007 . met", "al. 2007 . met mediated", "2007 . met mediated activation", ". met mediated activation of", "met mediated activation of stat3", "mediated activation of stat3 is", "activation of stat3 is implicated", "of stat3 is implicated in", "stat3 is implicated in anchorage", "is implicated in anchorage independent", "implicated in anchorage independent cell", "in anchorage independent cell growth", "anchorage independent cell growth and", "independent cell growth and invasiveness", "cell growth and invasiveness downstream", "growth and invasiveness downstream of", "and invasiveness downstream of hgf", "downstream of hgf zhang", "of hgf zhang et", "hgf zhang et al.", "et al. 2005 . met", "al. 2005 . met can", "2005 . met can also", ". met can also interact", "met can also interact with", "can also interact with stat1a", "interact with stat1a stat1b", "with stat1a stat1b and", "stat1a stat1b and stat5", "stat1b and stat5 but", "and stat5 but the", "stat5 but the biological", "but the biological importance of", "the biological importance of these", "biological importance of these interactions", "importance of these interactions is", "of these interactions is not", "these interactions is not known", "is not known runge", "not known runge et", "known runge et al.", "runge et al. 1999 ." ] }, { "record_id": "GLY_000594_1_1504", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8934593", "r hsa", "hsa 8934593", "r hsa 8934593" ] }, { "record_id": "GLY_000594_1_1504", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of runx1", "runx1 expression", "expression and", "and activity", "regulation of runx1", "of runx1 expression", "runx1 expression and", "expression and activity", "regulation of runx1 expression", "of runx1 expression and", "runx1 expression and activity", "regulation of runx1 expression and", "of runx1 expression and activity", "at the", "the level", "level of", "of transcription", "expression of", "of the", "the runx1", "runx1 transcription", "transcription factor", "factor is", "is regulated", "regulated by", "by two", "two alternative", "alternative promoters:", "promoters: a", "a distal", "distal promoter", "and a", "a proximal", "proximal promoter", "p2. p1", "p1 is", "is more", "more than", "than 7", "7 kb", "kb upstream", "upstream of", "of p2", "ghozi et", "et al.", "al. 1996", "1996 .", ". in", "in mice", "runx1 gene", "gene is", "is preferentially", "preferentially transcribed", "transcribed from", "from the", "the proximal", "proximal p2", "p2 promoter", "promoter during", "during generation", "generation of", "of hematopoietic", "hematopoietic cells", "cells from", "from hemogenic", "hemogenic endothelium.", "endothelium. in", "in fully", "fully committed", "committed hematopoietic", "hematopoietic progenitors", "the distal", "distal p1", "p1 promoter", "sroczynska et", "al. 2009", "bee et", "al. 2010", "2010 .", "in human", "human t", "t cells", "runx1 is", "from p1", "p1 throughout", "throughout development", "while developing", "developing natural", "natural killer", "killer cells", "cells transcribe", "transcribe runx1", "runx1 predominantly", "predominantly from", "from p2.", "p2. developing", "developing b", "b cells", "transcribe low", "low levels", "levels of", "runx1 from", "from both", "both promoters", "telfer and", "and rothenberg", "rothenberg 2001", "2001 .
              runx1", ".
              runx1 mrnas", "mrnas transcribed", "from alternative", "alternative promoters", "promoters differ", "differ in", "in their", "their 5'utrs", "5'utrs and", "and splicing", "splicing isoforms", "isoforms of", "runx1 have", "have also", "also been", "been described.", "described. the", "the function", "function of", "of alternative", "alternative splice", "splice isoforms", "isoforms and", "and alternative", "alternative 5'utrs", "5'utrs has", "has not", "not been", "been fully", "fully elucidated", "challen and", "and goodell", "goodell 2010", "komeno et", "al. 2014", "2014 .
              during", ".
              during zebrafish", "zebrafish hematopoiesis", "expression increases", "increases in", "in response", "response to", "to notch", "notch signaling", "but direct", "direct transcriptional", "transcriptional regulation", "runx1 by", "by notch", "notch has", "been demonstrated", "burns et", "al. 2005", "2005 .", ". runx1", "transcription also", "also increases", "to wnt", "wnt signaling.", "signaling. bothtcf7", "bothtcf7 and", "and tcf4", "tcf4 bind", "bind the", "runx1 promoter", "wu et", "al. 2012", "hoverter et", "and runx1", "transcription driven", "driven by", "by the", "the tcf", "tcf binding", "binding element", "to wnt3a", "wnt3a treatment", "treatment is", "is inhibited", "inhibited by", "the dominant", "dominant negative", "negative mutant", "mutant of", "of tcf4", "medina et", "al. 2016", "2016 .", "in developing", "developing mouse", "mouse ovary", "expression is", "is positively", "positively regulated", "by wnt4", "wnt4 signaling", "naillat et", "al. 2015", "2015 .
              studies", ".
              studies in", "in mouse", "mouse hematopoietic", "hematopoietic stem", "stem and", "and progenitor", "progenitor cells", "cells imply", "imply that", "that runx1", "runx1 may", "may be", "be a", "a direct", "transcriptional target", "target of", "of hoxb4", "oshima et", "al. 2011", "2011 .
              conserved", ".
              conserved cis", "cis regulatory", "regulatory elements", "elements were", "were recently", "recently identified", "identified in", "in intron", "intron 5", "5 of", "of runx1.", "runx1. the", "runx1 breakpoints", "breakpoints observed", "observed in", "in acute", "acute myeloid", "myeloid leukemia", "with translocation", "8 21", "which result", "result in", "in expression", "of a", "a fusion", "fusion runx1", "runx1 eto", "eto protein", "cluster in", "in proximity", "proximity to", "to these", "these not", "not yet", "yet fully", "fully characterized", "characterized cis", "rebolledo jaramillo", "jaramillo et", "2014 .
              at", ".
              at the", "of translation", "by various", "various micrornas", "micrornas which", "which bind", "bind to", "to the", "the 3'utr", "3'utr of", "runx1 mrna", "mrna and", "and inhibit", "inhibit its", "its translation", "translation through", "through endonucleolytic", "endonucleolytic and/or", "and/or nonendonucleolytic", "nonendonucleolytic mechanisms.", "mechanisms. micrornas", "micrornas that", "that target", "target runx1", "runx1 include", "include mir", "mir 378", "browne et", "mir 302b", "ge et", "mir 18a", "miao et", "mir 675", "zhuang et", "mir 27a", "ben ami", "ami et", "mir 17", "mir 20a", "fontana et", "al. 2007", "and mir", "mir 215", "li et", "2016 .
              at", "the posttranslational", "posttranslational level", "runx1 activity", "activity is", "by postranslational", "postranslational modifications", "modifications and", "and binding", "binding to", "to co", "co factors.", "factors. src", "src family", "family kinases", "kinases phosphorylate", "phosphorylate runx1", "runx1 on", "on multiple", "multiple tyrosine", "tyrosine residues", "residues in", "in the", "the negative", "negative regulatory", "regulatory domain", "involved in", "in autoinhibition", "autoinhibition of", "runx1. runx1", "runx1 tyrosine", "tyrosine phosphorylation", "phosphorylation correlates", "correlates with", "with reduced", "reduced binding", "binding of", "runx1 to", "to gata1", "gata1 and", "and increased", "increased binding", "the swi/snf", "swi/snf complex", "leading to", "to inhibition", "inhibition of", "runx1 mediated", "mediated differentiation", "differentiation of", "of t", "cells and", "and megakaryocytes.", "megakaryocytes. shp2", "tyrosine phosphatase", "phosphatase binds", "binds to", "to runx1", "runx1 and", "and dephosphorylates", "dephosphorylates it", "huang et", "2012 .
              formation", ".
              formation of", "the complex", "complex with", "with cbfb", "cbfb is", "is necessary", "necessary for", "for the", "the transcriptional", "transcriptional activity", "activity of", "wang et", ". binding", "of ccnd3", "ccnd3 and", "and probably", "probably other", "other two", "two cyclin", "cyclin d", "d family", "family members", "ccnd1 and", "and ccnd2", "runx1 inhibits", "inhibits its", "its association", "association with", "peterson et", "while binding", "to cdk6", "cdk6 interferes", "interferes with", "with binding", "to dna", "dna without", "without affecting", "affecting formation", "formation of", "the runx1:cbfb", "runx1:cbfb complex.", "complex. binding", "to pml", "pml plays", "plays a", "a role", "role in", "in subnuclear", "subnuclear targeting", "targeting of", "nguyen et", "2005 .
              runx1", ".
              runx1 activity", "activity and", "and protein", "protein levels", "levels vary", "vary during", "during the", "the cell", "cell cycle.", "cycle. runx1", "runx1 protein", "levels increase", "increase from", "from g1", "g1 to", "to s", "s and", "and from", "from s", "s to", "to g2", "g2 phases", "with no", "no increase", "increase in", "in runx1", "mrna levels.", "levels. cdk1", "cdk1 mediated", "mediated phosphorylation", "phosphorylation of", "runx1 at", "the g2/m", "g2/m transition", "transition is", "is implicated", "implicated in", "in reduction", "reduction of", "runx1 transactivation", "transactivation potency", "potency and", "and may", "may promote", "promote runx1", "protein degradation", "degradation by", "the anaphase", "anaphase promoting", "promoting complex", "reviewed by", "by friedman", "friedman 2009", "2009 .", "at the level", "the level of", "level of transcription", "transcription expression", "expression of the", "of the runx1", "the runx1 transcription", "runx1 transcription factor", "transcription factor is", "factor is regulated", "is regulated by", "regulated by two", "by two alternative", "two alternative promoters:", "alternative promoters: a", "promoters: a distal", "a distal promoter", "promoter p1", "p1 and", "and a proximal", "a proximal promoter", "promoter p2.", "p2. p1 is", "p1 is more", "is more than", "more than 7", "than 7 kb", "7 kb upstream", "kb upstream of", "upstream of p2", "p2 ghozi", "ghozi et al.", "et al. 1996", "al. 1996 .", "1996 . in", ". in mice", "mice the", "the runx1 gene", "runx1 gene is", "gene is preferentially", "is preferentially transcribed", "preferentially transcribed from", "transcribed from the", "from the proximal", "the proximal p2", "proximal p2 promoter", "p2 promoter during", "promoter during generation", "during generation of", "generation of hematopoietic", "of hematopoietic cells", "hematopoietic cells from", "cells from hemogenic", "from hemogenic endothelium.", "hemogenic endothelium. in", "endothelium. in fully", "in fully committed", "fully committed hematopoietic", "committed hematopoietic progenitors", "progenitors the", "from the distal", "the distal p1", "distal p1 promoter", "promoter sroczynska", "sroczynska et al.", "et al. 2009", "2009 bee", "bee et al.", "et al. 2010", "al. 2010 .", "2010 . in", ". in human", "in human t", "human t cells", "cells runx1", "runx1 is preferentially", "transcribed from p1", "from p1 throughout", "p1 throughout development", "development while", "while developing natural", "developing natural killer", "natural killer cells", "killer cells transcribe", "cells transcribe runx1", "transcribe runx1 predominantly", "runx1 predominantly from", "predominantly from p2.", "from p2. developing", "p2. developing b", "developing b cells", "b cells transcribe", "cells transcribe low", "transcribe low levels", "low levels of", "levels of runx1", "of runx1 from", "runx1 from both", "from both promoters", "promoters telfer", "telfer and rothenberg", "and rothenberg 2001", "rothenberg 2001 .
              runx1", "2001 .
              runx1 mrnas", ".
              runx1 mrnas transcribed", "mrnas transcribed from", "transcribed from alternative", "from alternative promoters", "alternative promoters differ", "promoters differ in", "differ in their", "in their 5'utrs", "their 5'utrs and", "5'utrs and splicing", "and splicing isoforms", "splicing isoforms of", "isoforms of runx1", "of runx1 have", "runx1 have also", "have also been", "also been described.", "been described. the", "described. the function", "the function of", "function of alternative", "of alternative splice", "alternative splice isoforms", "splice isoforms and", "isoforms and alternative", "and alternative 5'utrs", "alternative 5'utrs has", "5'utrs has not", "has not been", "not been fully", "been fully elucidated", "elucidated challen", "challen and goodell", "and goodell 2010", "2010 komeno", "komeno et al.", "et al. 2014", "al. 2014 .
              during", "2014 .
              during zebrafish", ".
              during zebrafish hematopoiesis", "hematopoiesis runx1", "runx1 expression increases", "expression increases in", "increases in response", "in response to", "response to notch", "to notch signaling", "signaling but", "but direct transcriptional", "direct transcriptional regulation", "transcriptional regulation of", "of runx1 by", "runx1 by notch", "by notch has", "notch has not", "not been demonstrated", "demonstrated burns", "burns et al.", "et al. 2005", "al. 2005 .", "2005 . runx1", ". runx1 transcription", "runx1 transcription also", "transcription also increases", "also increases in", "response to wnt", "to wnt signaling.", "wnt signaling. bothtcf7", "signaling. bothtcf7 and", "bothtcf7 and tcf4", "and tcf4 bind", "tcf4 bind the", "bind the runx1", "the runx1 promoter", "promoter wu", "wu et al.", "et al. 2012", "2012 hoverter", "hoverter et al.", "and runx1 transcription", "runx1 transcription driven", "transcription driven by", "driven by the", "by the tcf", "the tcf binding", "tcf binding element", "element tbe", "tbe in", "response to wnt3a", "to wnt3a treatment", "wnt3a treatment is", "treatment is inhibited", "is inhibited by", "inhibited by the", "by the dominant", "the dominant negative", "dominant negative mutant", "negative mutant of", "mutant of tcf4", "tcf4 medina", "medina et al.", "et al. 2016", "al. 2016 .", "2016 . in", ". in developing", "in developing mouse", "developing mouse ovary", "ovary runx1", "runx1 expression is", "expression is positively", "is positively regulated", "positively regulated by", "regulated by wnt4", "by wnt4 signaling", "signaling naillat", "naillat et al.", "et al. 2015", "al. 2015 .
              studies", "2015 .
              studies in", ".
              studies in mouse", "in mouse hematopoietic", "mouse hematopoietic stem", "hematopoietic stem and", "stem and progenitor", "and progenitor cells", "progenitor cells imply", "cells imply that", "imply that runx1", "that runx1 may", "runx1 may be", "may be a", "be a direct", "a direct transcriptional", "direct transcriptional target", "transcriptional target of", "target of hoxb4", "hoxb4 oshima", "oshima et al.", "et al. 2011", "al. 2011 .
              conserved", "2011 .
              conserved cis", ".
              conserved cis regulatory", "cis regulatory elements", "regulatory elements were", "elements were recently", "were recently identified", "recently identified in", "identified in intron", "in intron 5", "intron 5 of", "5 of runx1.", "of runx1. the", "runx1. the runx1", "the runx1 breakpoints", "runx1 breakpoints observed", "breakpoints observed in", "observed in acute", "in acute myeloid", "acute myeloid leukemia", "leukemia aml", "aml with", "translocation 8", "which result in", "result in expression", "in expression of", "expression of a", "of a fusion", "a fusion runx1", "fusion runx1 eto", "runx1 eto protein", "protein cluster", "cluster in intron", "5 in", "in proximity to", "proximity to these", "to these not", "these not yet", "not yet fully", "yet fully characterized", "fully characterized cis", "characterized cis regulatory", "elements rebolledo", "rebolledo jaramillo et", "jaramillo et al.", "al. 2014 .
              at", "2014 .
              at the", ".
              at the level", "level of translation", "translation runx1", "expression is regulated", "regulated by various", "by various micrornas", "various micrornas which", "micrornas which bind", "which bind to", "bind to the", "to the 3'utr", "the 3'utr of", "3'utr of runx1", "of runx1 mrna", "runx1 mrna and", "mrna and inhibit", "and inhibit its", "inhibit its translation", "its translation through", "translation through endonucleolytic", "through endonucleolytic and/or", "endonucleolytic and/or nonendonucleolytic", "and/or nonendonucleolytic mechanisms.", "nonendonucleolytic mechanisms. micrornas", "mechanisms. micrornas that", "micrornas that target", "that target runx1", "target runx1 include", "runx1 include mir", "include mir 378", "378 browne", "browne et al.", "302b ge", "ge et al.", "18a miao", "miao et al.", "675 zhuang", "zhuang et al.", "27a ben", "ben ami et", "ami et al.", "17 mir", "20a mir106", "mir106 fontana", "fontana et al.", "et al. 2007", "2007 and", "and mir 215", "215 li", "li et al.", "al. 2016 .
              at", "2016 .
              at the", ".
              at the posttranslational", "the posttranslational level", "level runx1", "runx1 activity is", "activity is regulated", "regulated by postranslational", "by postranslational modifications", "postranslational modifications and", "modifications and binding", "and binding to", "binding to co", "to co factors.", "co factors. src", "factors. src family", "src family kinases", "family kinases phosphorylate", "kinases phosphorylate runx1", "phosphorylate runx1 on", "runx1 on multiple", "on multiple tyrosine", "multiple tyrosine residues", "tyrosine residues in", "residues in the", "in the negative", "the negative regulatory", "negative regulatory domain", "domain involved", "involved in autoinhibition", "in autoinhibition of", "autoinhibition of runx1.", "of runx1. runx1", "runx1. runx1 tyrosine", "runx1 tyrosine phosphorylation", "tyrosine phosphorylation correlates", "phosphorylation correlates with", "correlates with reduced", "with reduced binding", "reduced binding of", "binding of runx1", "of runx1 to", "runx1 to gata1", "to gata1 and", "gata1 and increased", "and increased binding", "increased binding of", "runx1 to the", "to the swi/snf", "the swi/snf complex", "complex leading", "leading to inhibition", "to inhibition of", "inhibition of runx1", "of runx1 mediated", "runx1 mediated differentiation", "mediated differentiation of", "differentiation of t", "of t cells", "t cells and", "cells and megakaryocytes.", "and megakaryocytes. shp2", "shp2 ptpn11", "ptpn11 tyrosine", "tyrosine phosphatase binds", "phosphatase binds to", "binds to runx1", "to runx1 and", "runx1 and dephosphorylates", "and dephosphorylates it", "it huang", "huang et al.", "al. 2012 .
              formation", "2012 .
              formation of", ".
              formation of the", "of the complex", "the complex with", "complex with cbfb", "with cbfb is", "cbfb is necessary", "is necessary for", "necessary for the", "for the transcriptional", "the transcriptional activity", "transcriptional activity of", "activity of runx1", "runx1 wang", "wang et al.", "1996 . binding", ". binding of", "binding of ccnd3", "of ccnd3 and", "ccnd3 and probably", "and probably other", "probably other two", "other two cyclin", "two cyclin d", "cyclin d family", "d family members", "members ccnd1", "ccnd1 and ccnd2", "ccnd2 to", "to runx1 inhibits", "runx1 inhibits its", "inhibits its association", "its association with", "association with cbfb", "cbfb peterson", "peterson et al.", "while binding to", "binding to cdk6", "to cdk6 interferes", "cdk6 interferes with", "interferes with binding", "with binding of", "runx1 to dna", "to dna without", "dna without affecting", "without affecting formation", "affecting formation of", "formation of the", "of the runx1:cbfb", "the runx1:cbfb complex.", "runx1:cbfb complex. binding", "complex. binding of", "runx1 to pml", "to pml plays", "pml plays a", "plays a role", "a role in", "role in subnuclear", "in subnuclear targeting", "subnuclear targeting of", "targeting of runx1", "runx1 nguyen", "nguyen et al.", "al. 2005 .
              runx1", "2005 .
              runx1 activity", ".
              runx1 activity and", "activity and protein", "and protein levels", "protein levels vary", "levels vary during", "vary during the", "during the cell", "the cell cycle.", "cell cycle. runx1", "cycle. runx1 protein", "runx1 protein levels", "protein levels increase", "levels increase from", "increase from g1", "from g1 to", "g1 to s", "to s and", "s and from", "and from s", "from s to", "s to g2", "to g2 phases", "phases with", "with no increase", "no increase in", "increase in runx1", "in runx1 mrna", "runx1 mrna levels.", "mrna levels. cdk1", "levels. cdk1 mediated", "cdk1 mediated phosphorylation", "mediated phosphorylation of", "phosphorylation of runx1", "of runx1 at", "runx1 at the", "at the g2/m", "the g2/m transition", "g2/m transition is", "transition is implicated", "is implicated in", "implicated in reduction", "in reduction of", "reduction of runx1", "of runx1 transactivation", "runx1 transactivation potency", "transactivation potency and", "potency and may", "and may promote", "may promote runx1", "promote runx1 protein", "runx1 protein degradation", "protein degradation by", "degradation by the", "by the anaphase", "the anaphase promoting", "anaphase promoting complex", "complex reviewed", "reviewed by friedman", "by friedman 2009", "friedman 2009 .", "at the level of", "the level of transcription", "of transcription expression", "transcription expression of", "expression of the runx1", "of the runx1 transcription", "the runx1 transcription factor", "runx1 transcription factor is", "transcription factor is regulated", "factor is regulated by", "is regulated by two", "regulated by two alternative", "by two alternative promoters:", "two alternative promoters: a", "alternative promoters: a distal", "promoters: a distal promoter", "distal promoter p1", "p1 and a", "and a proximal promoter", "proximal promoter p2.", "promoter p2. p1", "p2. p1 is more", "p1 is more than", "is more than 7", "more than 7 kb", "than 7 kb upstream", "7 kb upstream of", "kb upstream of p2", "of p2 ghozi", "p2 ghozi et", "ghozi et al. 1996", "et al. 1996 .", "al. 1996 . in", "1996 . in mice", "in mice the", "mice the runx1", "the runx1 gene is", "runx1 gene is preferentially", "gene is preferentially transcribed", "is preferentially transcribed from", "preferentially transcribed from the", "transcribed from the proximal", "from the proximal p2", "the proximal p2 promoter", "proximal p2 promoter during", "p2 promoter during generation", "promoter during generation of", "during generation of hematopoietic", "generation of hematopoietic cells", "of hematopoietic cells from", "hematopoietic cells from hemogenic", "cells from hemogenic endothelium.", "from hemogenic endothelium. in", "hemogenic endothelium. in fully", "endothelium. in fully committed", "in fully committed hematopoietic", "fully committed hematopoietic progenitors", "hematopoietic progenitors the", "progenitors the runx1", "transcribed from the distal", "from the distal p1", "the distal p1 promoter", "p1 promoter sroczynska", "promoter sroczynska et", "sroczynska et al. 2009", "al. 2009 bee", "2009 bee et", "bee et al. 2010", "et al. 2010 .", "al. 2010 . in", "2010 . in human", ". in human t", "in human t cells", "t cells runx1", "cells runx1 is", "runx1 is preferentially transcribed", "preferentially transcribed from p1", "transcribed from p1 throughout", "from p1 throughout development", "throughout development while", "development while developing", "while developing natural killer", "developing natural killer cells", "natural killer cells transcribe", "killer cells transcribe runx1", "cells transcribe runx1 predominantly", "transcribe runx1 predominantly from", "runx1 predominantly from p2.", "predominantly from p2. developing", "from p2. developing b", "p2. developing b cells", "developing b cells transcribe", "b cells transcribe low", "cells transcribe low levels", "transcribe low levels of", "low levels of runx1", "levels of runx1 from", "of runx1 from both", "runx1 from both promoters", "both promoters telfer", "promoters telfer and", "telfer and rothenberg 2001", "and rothenberg 2001 .
              runx1", "rothenberg 2001 .
              runx1 mrnas", "2001 .
              runx1 mrnas transcribed", ".
              runx1 mrnas transcribed from", "mrnas transcribed from alternative", "transcribed from alternative promoters", "from alternative promoters differ", "alternative promoters differ in", "promoters differ in their", "differ in their 5'utrs", "in their 5'utrs and", "their 5'utrs and splicing", "5'utrs and splicing isoforms", "and splicing isoforms of", "splicing isoforms of runx1", "isoforms of runx1 have", "of runx1 have also", "runx1 have also been", "have also been described.", "also been described. the", "been described. the function", "described. the function of", "the function of alternative", "function of alternative splice", "of alternative splice isoforms", "alternative splice isoforms and", "splice isoforms and alternative", "isoforms and alternative 5'utrs", "and alternative 5'utrs has", "alternative 5'utrs has not", "5'utrs has not been", "has not been fully", "not been fully elucidated", "fully elucidated challen", "elucidated challen and", "challen and goodell 2010", "goodell 2010 komeno", "2010 komeno et", "komeno et al. 2014", "et al. 2014 .
              during", "al. 2014 .
              during zebrafish", "2014 .
              during zebrafish hematopoiesis", "zebrafish hematopoiesis runx1", "hematopoiesis runx1 expression", "runx1 expression increases in", "expression increases in response", "increases in response to", "in response to notch", "response to notch signaling", "notch signaling but", "signaling but direct", "but direct transcriptional regulation", "direct transcriptional regulation of", "transcriptional regulation of runx1", "regulation of runx1 by", "of runx1 by notch", "runx1 by notch has", "by notch has not", "notch has not been", "has not been demonstrated", "been demonstrated burns", "demonstrated burns et", "burns et al. 2005", "et al. 2005 .", "al. 2005 . runx1", "2005 . runx1 transcription", ". runx1 transcription also", "runx1 transcription also increases", "transcription also increases in", "also increases in response", "in response to wnt", "response to wnt signaling.", "to wnt signaling. bothtcf7", "wnt signaling. bothtcf7 and", "signaling. bothtcf7 and tcf4", "bothtcf7 and tcf4 bind", "and tcf4 bind the", "tcf4 bind the runx1", "bind the runx1 promoter", "runx1 promoter wu", "promoter wu et", "wu et al. 2012", "al. 2012 hoverter", "2012 hoverter et", "hoverter et al. 2012", "2012 and", "and runx1 transcription driven", "runx1 transcription driven by", "transcription driven by the", "driven by the tcf", "by the tcf binding", "the tcf binding element", "binding element tbe", "tbe in response", "in response to wnt3a", "response to wnt3a treatment", "to wnt3a treatment is", "wnt3a treatment is inhibited", "treatment is inhibited by", "is inhibited by the", "inhibited by the dominant", "by the dominant negative", "the dominant negative mutant", "dominant negative mutant of", "negative mutant of tcf4", "of tcf4 medina", "tcf4 medina et", "medina et al. 2016", "et al. 2016 .", "al. 2016 . in", "2016 . in developing", ". in developing mouse", "in developing mouse ovary", "mouse ovary runx1", "ovary runx1 expression", "runx1 expression is positively", "expression is positively regulated", "is positively regulated by", "positively regulated by wnt4", "regulated by wnt4 signaling", "wnt4 signaling naillat", "signaling naillat et", "naillat et al. 2015", "et al. 2015 .
              studies", "al. 2015 .
              studies in", "2015 .
              studies in mouse", ".
              studies in mouse hematopoietic", "in mouse hematopoietic stem", "mouse hematopoietic stem and", "hematopoietic stem and progenitor", "stem and progenitor cells", "and progenitor cells imply", "progenitor cells imply that", "cells imply that runx1", "imply that runx1 may", "that runx1 may be", "runx1 may be a", "may be a direct", "be a direct transcriptional", "a direct transcriptional target", "direct transcriptional target of", "transcriptional target of hoxb4", "of hoxb4 oshima", "hoxb4 oshima et", "oshima et al. 2011", "et al. 2011 .
              conserved", "al. 2011 .
              conserved cis", "2011 .
              conserved cis regulatory", ".
              conserved cis regulatory elements", "cis regulatory elements were", "regulatory elements were recently", "elements were recently identified", "were recently identified in", "recently identified in intron", "identified in intron 5", "in intron 5 of", "intron 5 of runx1.", "5 of runx1. the", "of runx1. the runx1", "runx1. the runx1 breakpoints", "the runx1 breakpoints observed", "runx1 breakpoints observed in", "breakpoints observed in acute", "observed in acute myeloid", "in acute myeloid leukemia", "myeloid leukemia aml", "aml with translocation", "with translocation 8", "translocation 8 21", "21 which", "which result in expression", "result in expression of", "in expression of a", "expression of a fusion", "of a fusion runx1", "a fusion runx1 eto", "fusion runx1 eto protein", "eto protein cluster", "protein cluster in", "cluster in intron 5", "intron 5 in", "5 in proximity", "in proximity to these", "proximity to these not", "to these not yet", "these not yet fully", "not yet fully characterized", "yet fully characterized cis", "fully characterized cis regulatory", "characterized cis regulatory elements", "regulatory elements rebolledo", "elements rebolledo jaramillo", "rebolledo jaramillo et al.", "jaramillo et al. 2014", "et al. 2014 .
              at", "al. 2014 .
              at the", "2014 .
              at the level", ".
              at the level of", "the level of translation", "of translation runx1", "translation runx1 expression", "runx1 expression is regulated", "expression is regulated by", "is regulated by various", "regulated by various micrornas", "by various micrornas which", "various micrornas which bind", "micrornas which bind to", "which bind to the", "bind to the 3'utr", "to the 3'utr of", "the 3'utr of runx1", "3'utr of runx1 mrna", "of runx1 mrna and", "runx1 mrna and inhibit", "mrna and inhibit its", "and inhibit its translation", "inhibit its translation through", "its translation through endonucleolytic", "translation through endonucleolytic and/or", "through endonucleolytic and/or nonendonucleolytic", "endonucleolytic and/or nonendonucleolytic mechanisms.", "and/or nonendonucleolytic mechanisms. micrornas", "nonendonucleolytic mechanisms. micrornas that", "mechanisms. micrornas that target", "micrornas that target runx1", "that target runx1 include", "target runx1 include mir", "runx1 include mir 378", "mir 378 browne", "378 browne et", "browne et al. 2016", "2016 mir", "mir 302b ge", "302b ge et", "ge et al. 2014", "2014 mir", "mir 18a miao", "18a miao et", "miao et al. 2015", "2015 mir", "mir 675 zhuang", "675 zhuang et", "zhuang et al. 2014", "mir 27a ben", "27a ben ami", "ben ami et al.", "ami et al. 2009", "2009 mir", "mir 17 mir", "17 mir 20a", "mir 20a mir106", "mir106 fontana et", "fontana et al. 2007", "al. 2007 and", "2007 and mir", "mir 215 li", "215 li et", "li et al. 2016", "et al. 2016 .
              at", "al. 2016 .
              at the", "2016 .
              at the posttranslational", ".
              at the posttranslational level", "posttranslational level runx1", "level runx1 activity", "runx1 activity is regulated", "activity is regulated by", "is regulated by postranslational", "regulated by postranslational modifications", "by postranslational modifications and", "postranslational modifications and binding", "modifications and binding to", "and binding to co", "binding to co factors.", "to co factors. src", "co factors. src family", "factors. src family kinases", "src family kinases phosphorylate", "family kinases phosphorylate runx1", "kinases phosphorylate runx1 on", "phosphorylate runx1 on multiple", "runx1 on multiple tyrosine", "on multiple tyrosine residues", "multiple tyrosine residues in", "tyrosine residues in the", "residues in the negative", "in the negative regulatory", "the negative regulatory domain", "regulatory domain involved", "domain involved in", "involved in autoinhibition of", "in autoinhibition of runx1.", "autoinhibition of runx1. runx1", "of runx1. runx1 tyrosine", "runx1. runx1 tyrosine phosphorylation", "runx1 tyrosine phosphorylation correlates", "tyrosine phosphorylation correlates with", "phosphorylation correlates with reduced", "correlates with reduced binding", "with reduced binding of", "reduced binding of runx1", "binding of runx1 to", "of runx1 to gata1", "runx1 to gata1 and", "to gata1 and increased", "gata1 and increased binding", "and increased binding of", "increased binding of runx1", "of runx1 to the", "runx1 to the swi/snf", "to the swi/snf complex", "swi/snf complex leading", "complex leading to", "leading to inhibition of", "to inhibition of runx1", "inhibition of runx1 mediated", "of runx1 mediated differentiation", "runx1 mediated differentiation of", "mediated differentiation of t", "differentiation of t cells", "of t cells and", "t cells and megakaryocytes.", "cells and megakaryocytes. shp2", "megakaryocytes. shp2 ptpn11", "ptpn11 tyrosine phosphatase", "tyrosine phosphatase binds to", "phosphatase binds to runx1", "binds to runx1 and", "to runx1 and dephosphorylates", "runx1 and dephosphorylates it", "dephosphorylates it huang", "it huang et", "huang et al. 2012", "et al. 2012 .
              formation", "al. 2012 .
              formation of", "2012 .
              formation of the", ".
              formation of the complex", "of the complex with", "the complex with cbfb", "complex with cbfb is", "with cbfb is necessary", "cbfb is necessary for", "is necessary for the", "necessary for the transcriptional", "for the transcriptional activity", "the transcriptional activity of", "transcriptional activity of runx1", "of runx1 wang", "runx1 wang et", "wang et al. 1996", "al. 1996 . binding", "1996 . binding of", ". binding of ccnd3", "binding of ccnd3 and", "of ccnd3 and probably", "ccnd3 and probably other", "and probably other two", "probably other two cyclin", "other two cyclin d", "two cyclin d family", "cyclin d family members", "family members ccnd1", "members ccnd1 and", "and ccnd2 to", "ccnd2 to runx1", "to runx1 inhibits its", "runx1 inhibits its association", "inhibits its association with", "its association with cbfb", "with cbfb peterson", "cbfb peterson et", "peterson et al. 2005", "2005 while", "while binding to cdk6", "binding to cdk6 interferes", "to cdk6 interferes with", "cdk6 interferes with binding", "interferes with binding of", "with binding of runx1", "of runx1 to dna", "runx1 to dna without", "to dna without affecting", "dna without affecting formation", "without affecting formation of", "affecting formation of the", "formation of the runx1:cbfb", "of the runx1:cbfb complex.", "the runx1:cbfb complex. binding", "runx1:cbfb complex. binding of", "complex. binding of runx1", "of runx1 to pml", "runx1 to pml plays", "to pml plays a", "pml plays a role", "plays a role in", "a role in subnuclear", "role in subnuclear targeting", "in subnuclear targeting of", "subnuclear targeting of runx1", "of runx1 nguyen", "runx1 nguyen et", "nguyen et al. 2005", "et al. 2005 .
              runx1", "al. 2005 .
              runx1 activity", "2005 .
              runx1 activity and", ".
              runx1 activity and protein", "activity and protein levels", "and protein levels vary", "protein levels vary during", "levels vary during the", "vary during the cell", "during the cell cycle.", "the cell cycle. runx1", "cell cycle. runx1 protein", "cycle. runx1 protein levels", "runx1 protein levels increase", "protein levels increase from", "levels increase from g1", "increase from g1 to", "from g1 to s", "g1 to s and", "to s and from", "s and from s", "and from s to", "from s to g2", "s to g2 phases", "g2 phases with", "phases with no", "with no increase in", "no increase in runx1", "increase in runx1 mrna", "in runx1 mrna levels.", "runx1 mrna levels. cdk1", "mrna levels. cdk1 mediated", "levels. cdk1 mediated phosphorylation", "cdk1 mediated phosphorylation of", "mediated phosphorylation of runx1", "phosphorylation of runx1 at", "of runx1 at the", "runx1 at the g2/m", "at the g2/m transition", "the g2/m transition is", "g2/m transition is implicated", "transition is implicated in", "is implicated in reduction", "implicated in reduction of", "in reduction of runx1", "reduction of runx1 transactivation", "of runx1 transactivation potency", "runx1 transactivation potency and", "transactivation potency and may", "potency and may promote", "and may promote runx1", "may promote runx1 protein", "promote runx1 protein degradation", "runx1 protein degradation by", "protein degradation by the", "degradation by the anaphase", "by the anaphase promoting", "the anaphase promoting complex", "promoting complex reviewed", "complex reviewed by", "reviewed by friedman 2009", "by friedman 2009 .", "at the level of transcription", "level of transcription expression", "of transcription expression of", "transcription expression of the", "expression of the runx1 transcription", "of the runx1 transcription factor", "the runx1 transcription factor is", "runx1 transcription factor is regulated", "transcription factor is regulated by", "factor is regulated by two", "is regulated by two alternative", "regulated by two alternative promoters:", "by two alternative promoters: a", "two alternative promoters: a distal", "alternative promoters: a distal promoter", "a distal promoter p1", "promoter p1 and", "p1 and a proximal", "a proximal promoter p2.", "proximal promoter p2. p1", "promoter p2. p1 is", "p2. p1 is more than", "p1 is more than 7", "is more than 7 kb", "more than 7 kb upstream", "than 7 kb upstream of", "7 kb upstream of p2", "upstream of p2 ghozi", "of p2 ghozi et", "p2 ghozi et al.", "ghozi et al. 1996 .", "et al. 1996 . in", "al. 1996 . in mice", ". in mice the", "in mice the runx1", "mice the runx1 gene", "the runx1 gene is preferentially", "runx1 gene is preferentially transcribed", "gene is preferentially transcribed from", "is preferentially transcribed from the", "preferentially transcribed from the proximal", "transcribed from the proximal p2", "from the proximal p2 promoter", "the proximal p2 promoter during", "proximal p2 promoter during generation", "p2 promoter during generation of", "promoter during generation of hematopoietic", "during generation of hematopoietic cells", "generation of hematopoietic cells from", "of hematopoietic cells from hemogenic", "hematopoietic cells from hemogenic endothelium.", "cells from hemogenic endothelium. in", "from hemogenic endothelium. in fully", "hemogenic endothelium. in fully committed", "endothelium. in fully committed hematopoietic", "in fully committed hematopoietic progenitors", "committed hematopoietic progenitors the", "hematopoietic progenitors the runx1", "progenitors the runx1 gene", "preferentially transcribed from the distal", "transcribed from the distal p1", "from the distal p1 promoter", "distal p1 promoter sroczynska", "p1 promoter sroczynska et", "promoter sroczynska et al.", "et al. 2009 bee", "al. 2009 bee et", "2009 bee et al.", "bee et al. 2010 .", "et al. 2010 . in", "al. 2010 . in human", "2010 . in human t", ". in human t cells", "human t cells runx1", "t cells runx1 is", "cells runx1 is preferentially", "runx1 is preferentially transcribed from", "is preferentially transcribed from p1", "preferentially transcribed from p1 throughout", "transcribed from p1 throughout development", "p1 throughout development while", "throughout development while developing", "development while developing natural", "while developing natural killer cells", "developing natural killer cells transcribe", "natural killer cells transcribe runx1", "killer cells transcribe runx1 predominantly", "cells transcribe runx1 predominantly from", "transcribe runx1 predominantly from p2.", "runx1 predominantly from p2. developing", "predominantly from p2. developing b", "from p2. developing b cells", "p2. developing b cells transcribe", "developing b cells transcribe low", "b cells transcribe low levels", "cells transcribe low levels of", "transcribe low levels of runx1", "low levels of runx1 from", "levels of runx1 from both", "of runx1 from both promoters", "from both promoters telfer", "both promoters telfer and", "promoters telfer and rothenberg", "telfer and rothenberg 2001 .
              runx1", "and rothenberg 2001 .
              runx1 mrnas", "rothenberg 2001 .
              runx1 mrnas transcribed", "2001 .
              runx1 mrnas transcribed from", ".
              runx1 mrnas transcribed from alternative", "mrnas transcribed from alternative promoters", "transcribed from alternative promoters differ", "from alternative promoters differ in", "alternative promoters differ in their", "promoters differ in their 5'utrs", "differ in their 5'utrs and", "in their 5'utrs and splicing", "their 5'utrs and splicing isoforms", "5'utrs and splicing isoforms of", "and splicing isoforms of runx1", "splicing isoforms of runx1 have", "isoforms of runx1 have also", "of runx1 have also been", "runx1 have also been described.", "have also been described. the", "also been described. the function", "been described. the function of", "described. the function of alternative", "the function of alternative splice", "function of alternative splice isoforms", "of alternative splice isoforms and", "alternative splice isoforms and alternative", "splice isoforms and alternative 5'utrs", "isoforms and alternative 5'utrs has", "and alternative 5'utrs has not", "alternative 5'utrs has not been", "5'utrs has not been fully", "has not been fully elucidated", "been fully elucidated challen", "fully elucidated challen and", "elucidated challen and goodell", "and goodell 2010 komeno", "goodell 2010 komeno et", "2010 komeno et al.", "komeno et al. 2014 .
              during", "et al. 2014 .
              during zebrafish", "al. 2014 .
              during zebrafish hematopoiesis", ".
              during zebrafish hematopoiesis runx1", "zebrafish hematopoiesis runx1 expression", "hematopoiesis runx1 expression increases", "runx1 expression increases in response", "expression increases in response to", "increases in response to notch", "in response to notch signaling", "to notch signaling but", "notch signaling but direct", "signaling but direct transcriptional", "but direct transcriptional regulation of", "direct transcriptional regulation of runx1", "transcriptional regulation of runx1 by", "regulation of runx1 by notch", "of runx1 by notch has", "runx1 by notch has not", "by notch has not been", "notch has not been demonstrated", "not been demonstrated burns", "been demonstrated burns et", "demonstrated burns et al.", "burns et al. 2005 .", "et al. 2005 . runx1", "al. 2005 . runx1 transcription", "2005 . runx1 transcription also", ". runx1 transcription also increases", "runx1 transcription also increases in", "transcription also increases in response", "also increases in response to", "increases in response to wnt", "in response to wnt signaling.", "response to wnt signaling. bothtcf7", "to wnt signaling. bothtcf7 and", "wnt signaling. bothtcf7 and tcf4", "signaling. bothtcf7 and tcf4 bind", "bothtcf7 and tcf4 bind the", "and tcf4 bind the runx1", "tcf4 bind the runx1 promoter", "the runx1 promoter wu", "runx1 promoter wu et", "promoter wu et al.", "et al. 2012 hoverter", "al. 2012 hoverter et", "2012 hoverter et al.", "al. 2012 and", "2012 and runx1", "and runx1 transcription driven by", "runx1 transcription driven by the", "transcription driven by the tcf", "driven by the tcf binding", "by the tcf binding element", "tcf binding element tbe", "element tbe in", "tbe in response to", "in response to wnt3a treatment", "response to wnt3a treatment is", "to wnt3a treatment is inhibited", "wnt3a treatment is inhibited by", "treatment is inhibited by the", "is inhibited by the dominant", "inhibited by the dominant negative", "by the dominant negative mutant", "the dominant negative mutant of", "dominant negative mutant of tcf4", "mutant of tcf4 medina", "of tcf4 medina et", "tcf4 medina et al.", "medina et al. 2016 .", "et al. 2016 . in", "al. 2016 . in developing", "2016 . in developing mouse", ". in developing mouse ovary", "developing mouse ovary runx1", "mouse ovary runx1 expression", "ovary runx1 expression is", "runx1 expression is positively regulated", "expression is positively regulated by", "is positively regulated by wnt4", "positively regulated by wnt4 signaling", "by wnt4 signaling naillat", "wnt4 signaling naillat et", "signaling naillat et al.", "naillat et al. 2015 .
              studies", "et al. 2015 .
              studies in", "al. 2015 .
              studies in mouse", "2015 .
              studies in mouse hematopoietic", ".
              studies in mouse hematopoietic stem", "in mouse hematopoietic stem and", "mouse hematopoietic stem and progenitor", "hematopoietic stem and progenitor cells", "stem and progenitor cells imply", "and progenitor cells imply that", "progenitor cells imply that runx1", "cells imply that runx1 may", "imply that runx1 may be", "that runx1 may be a", "runx1 may be a direct", "may be a direct transcriptional", "be a direct transcriptional target", "a direct transcriptional target of", "direct transcriptional target of hoxb4", "target of hoxb4 oshima", "of hoxb4 oshima et", "hoxb4 oshima et al.", "oshima et al. 2011 .
              conserved", "et al. 2011 .
              conserved cis", "al. 2011 .
              conserved cis regulatory", "2011 .
              conserved cis regulatory elements", ".
              conserved cis regulatory elements were", "cis regulatory elements were recently", "regulatory elements were recently identified", "elements were recently identified in", "were recently identified in intron", "recently identified in intron 5", "identified in intron 5 of", "in intron 5 of runx1.", "intron 5 of runx1. the", "5 of runx1. the runx1", "of runx1. the runx1 breakpoints", "runx1. the runx1 breakpoints observed", "the runx1 breakpoints observed in", "runx1 breakpoints observed in acute", "breakpoints observed in acute myeloid", "observed in acute myeloid leukemia", "acute myeloid leukemia aml", "leukemia aml with", "with translocation 8 21", "8 21 which", "21 which result", "which result in expression of", "result in expression of a", "in expression of a fusion", "expression of a fusion runx1", "of a fusion runx1 eto", "a fusion runx1 eto protein", "runx1 eto protein cluster", "eto protein cluster in", "protein cluster in intron", "in intron 5 in", "intron 5 in proximity", "5 in proximity to", "in proximity to these not", "proximity to these not yet", "to these not yet fully", "these not yet fully characterized", "not yet fully characterized cis", "yet fully characterized cis regulatory", "fully characterized cis regulatory elements", "cis regulatory elements rebolledo", "regulatory elements rebolledo jaramillo", "elements rebolledo jaramillo et", "rebolledo jaramillo et al. 2014", "jaramillo et al. 2014 .
              at", "et al. 2014 .
              at the", "al. 2014 .
              at the level", "2014 .
              at the level of", ".
              at the level of translation", "level of translation runx1", "of translation runx1 expression", "translation runx1 expression is", "runx1 expression is regulated by", "expression is regulated by various", "is regulated by various micrornas", "regulated by various micrornas which", "by various micrornas which bind", "various micrornas which bind to", "micrornas which bind to the", "which bind to the 3'utr", "bind to the 3'utr of", "to the 3'utr of runx1", "the 3'utr of runx1 mrna", "3'utr of runx1 mrna and", "of runx1 mrna and inhibit", "runx1 mrna and inhibit its", "mrna and inhibit its translation", "and inhibit its translation through", "inhibit its translation through endonucleolytic", "its translation through endonucleolytic and/or", "translation through endonucleolytic and/or nonendonucleolytic", "through endonucleolytic and/or nonendonucleolytic mechanisms.", "endonucleolytic and/or nonendonucleolytic mechanisms. micrornas", "and/or nonendonucleolytic mechanisms. micrornas that", "nonendonucleolytic mechanisms. micrornas that target", "mechanisms. micrornas that target runx1", "micrornas that target runx1 include", "that target runx1 include mir", "target runx1 include mir 378", "include mir 378 browne", "mir 378 browne et", "378 browne et al.", "al. 2016 mir", "2016 mir 302b", "mir 302b ge et", "302b ge et al.", "al. 2014 mir", "2014 mir 18a", "mir 18a miao et", "18a miao et al.", "al. 2015 mir", "2015 mir 675", "mir 675 zhuang et", "675 zhuang et al.", "2014 mir 27a", "mir 27a ben ami", "27a ben ami et", "ben ami et al. 2009", "al. 2009 mir", "2009 mir 17", "mir 17 mir 20a", "20a mir106 fontana", "mir106 fontana et al.", "et al. 2007 and", "al. 2007 and mir", "2007 and mir 215", "and mir 215 li", "mir 215 li et", "215 li et al.", "li et al. 2016 .
              at", "et al. 2016 .
              at the", "al. 2016 .
              at the posttranslational", "2016 .
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              formation", "et al. 2012 .
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              the", "2015 .

              the superoxide", ".

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              the", "al. 2015 .

              the superoxide", "2015 .

              the superoxide dismutates", ".

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"phosphatase non receptor type 11/shc", "non receptor type 11/shc transforming", "receptor type 11/shc transforming protein", "type 11/shc transforming protein 1", "11/shc transforming protein 1 or", "transforming protein 1 or 2", "1 or 2 cascade", "or 2 cascade activation", "cascade activation gadina et", "activation gadina et al.", "gadina et al. 2000 ." ] }, { "record_id": "GLY_000594_1_1517", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "8985947", "r hsa", "hsa 8985947", "r hsa 8985947" ] }, { "record_id": "GLY_000594_1_1517", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 9", "9 signaling", "interleukin 9 signaling", "binds interleukin", "9 receptor", "a chain", "and the", "the interleukin", "interleukin 2", "2 receptor", "receptor common", "common gamma", "gamma chain", "to initiate", "initiate il9", "il9 signaling", "signaling downstream", "downstream cascade.", "cascade. 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"lymphoma cells nizsal\u00f3czki et", "cells nizsal\u00f3czki et al.", "nizsal\u00f3czki et al. 2014 .", "et al. 2014 . il2rg", "al. 2014 . il2rg is", "2014 . il2rg is essential", ". il2rg is essential for", "il2rg is essential for il9", "is essential for il9 dependent", "essential for il9 dependent growth", "for il9 dependent growth signal", "il9 dependent growth signal transduction", "growth signal transduction kimura", "signal transduction kimura et", "transduction kimura et al.", "kimura et al. 1995 .", "et al. 1995 . il9r", "1995 . il9r glycoprotein", ". il9r glycoprotein of", "il9r glycoprotein of 64", "of 64 kda has", "64 kda has saturable", "kda has saturable and", "has saturable and specific binding", "saturable and specific binding sites", "and specific binding sites with", "specific binding sites with a", "binding sites with a kd", "sites with a kd of", "with a kd of 100", "a kd of 100 pm", "of 100 pm renauld", "100 pm renauld et", "pm renauld et al.", "renauld et al. 1992 .", "et al. 1992 . the", "al. 1992 . the activated", "1992 . the activated il9r", ". the activated il9r complex", "the activated il9r complex recruits", "activated il9r complex recruits tyrosine", "il9r complex recruits tyrosine kinase", "complex recruits tyrosine kinase proteins", "recruits tyrosine kinase proteins from", "tyrosine kinase proteins from the", "kinase proteins from the janus", "proteins from the janus kinase", "the janus kinase jak", "kinase jak family:", "jak1 jak1 and", "jak3 jak3 for", "jak3 for subsequent activation", "for subsequent activation of the", "subsequent activation of the signal", "activation of the signal transducer", "of the signal transducer and", "the signal transducer and activator", "signal transducer and activator of", "transducer and activator of transcription", "activator of transcription stat", "transcription stat factors", "factors stat1 stat3 and", "stat1 stat3 and stat5.", "stat3 and stat5. the activated", "and stat5. the activated stats", 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"9010642", "r hsa", "hsa 9010642", "r hsa 9010642" ] }, { "record_id": "GLY_000594_1_1519", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "robo receptors", "receptors bind", "bind akap5", "robo receptors bind", "receptors bind akap5", "robo receptors bind akap5", "also known", "known as", "as akap79", "akap79 in", "in humans", "humans and", "and akap150", "akap150 in", "in mice", "is an", "an a", "a kinase", "kinase anchoring", "anchoring protein", "protein which", "which is", "is able", "able to", "to bind", "bind to", "to robo", "receptors robo2", "robo2 and", "and robo3.1", "an isoform", "isoform of", "of robo3", "by interacting", "interacting with", "with their", "their cytoplasmic", "cytoplasmic tails.", "tails. the", "the interaction", "interaction was", "was originally", "originally detected", "detected between", "between endogenous", "endogenous proteins", "proteins from", "from the", "the mouse", "mouse brain", "brain lysates.", "lysates. akap5", "akap5 can", "can recruit", "recruit protein", "protein kinase", "kinase a", "kinase c", "and protein", "protein phosphatase", "phosphatase pp2b", "pp2b to", "to robo2.", "robo2. akap5", "akap5 mediated", "mediated recruitment", "recruitment of", "of pkc", "pkc to", "to robo3.1", "robo3.1 leads", "leads to", "to phosphorylation", "phosphorylation of", "of robo3.1", "robo3.1 by", "by pkc.", "pkc. functional", "functional implications", "implications of", "of akap5", "akap5 interaction", "interaction with", "with robo", "receptors are", "are not", "not known", "samelson et", "et al.", "al. 2015", "2015 .", "akap5 also", "also known as", "known as akap79", "as akap79 in", "akap79 in humans", "in humans and", "humans and akap150", "and akap150 in", "akap150 in mice", "mice is", "is an a", "an a kinase", "a kinase anchoring", "kinase anchoring protein", "anchoring protein which", "protein which is", "which is able", "is able to", "able to bind", "to bind to", "bind to robo", "to 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"akap79 in humans and akap150", "in humans and akap150 in", "humans and akap150 in mice", "akap150 in mice is", "in mice is an", "mice is an a", "is an a kinase anchoring", "an a kinase anchoring protein", "a kinase anchoring protein which", "kinase anchoring protein which is", "anchoring protein which is able", "protein which is able to", "which is able to bind", "is able to bind to", "able to bind to robo", "to bind to robo receptors", "bind to robo receptors robo2", "to robo receptors robo2 and", "robo receptors robo2 and robo3.1", "robo2 and robo3.1 an", "and robo3.1 an isoform", "robo3.1 an isoform of", "isoform of robo3 by", "of robo3 by interacting", "robo3 by interacting with", "by interacting with their cytoplasmic", "interacting with their cytoplasmic tails.", "with their cytoplasmic tails. the", "their cytoplasmic tails. the interaction", "cytoplasmic tails. the interaction was", "tails. the interaction was originally", "the interaction was originally detected", "interaction 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\u03c9 3", "\u03c9 3 fatty", "3 fatty acid", "fatty acid docosahexaenoic", "acid docosahexaenoic acid", "acid dha", "either via aspirin", "via aspirin triggered", "aspirin triggered cylcooxygenase", "triggered cylcooxygenase catalysis", "catalysis 17", "r at", "rvds or", "or via the", "via the lipoxygenase", "the lipoxygenase pathway", "pathway described", "here forming", "forming the epimeric", "the epimeric 17", "epimeric 17 s", "s rvd1", "rvd1 6 resolvins", "resolvins serhan", "serhan et al.", "et al. 2014", "2014 bannenberg", "bannenberg & serhan", "& serhan 2010", "serhan 2010 .", "the d series resolvins", "series resolvins rvd1", "resolvins rvd1 6", "rvd1 6 are", "6 are biosynthesised", "are biosynthesised from the", "biosynthesised from the precursor", "from the precursor \u03c9", "the precursor \u03c9 3", "precursor \u03c9 3 fatty", "\u03c9 3 fatty acid", "3 fatty acid docosahexaenoic", "fatty acid docosahexaenoic acid", "docosahexaenoic acid dha", "dha either", "either via 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2014 serhan", "al. 2014 serhan et", "2014 serhan et al." ] }, { "record_id": "GLY_000594_1_1523", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9018682", "r hsa", "hsa 9018682", "r hsa 9018682" ] }, { "record_id": "GLY_000594_1_1523", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biosynthesis of", "of maresins", "biosynthesis of maresins", "maresins 1", "1 and", "and 2", "mar1 and", "and mar2", "are derived", "derived through", "through the", "the action", "action of", "of lipoxygenase", "lipoxygenase 12", "12 on", "on the", "the \u03c9", "\u03c9 3", "3 fatty", "fatty acid", "acid docosahexaenoic", "docosahexaenoic acid", "dha .", ". mars", "mars are", "are mainly", "mainly produced", "produced by", "by macrophages", "macrophages hence", "hence the", "the derivation", "derivation of", "of the", "the name", "name from", "from macrophage", "macrophage mediator", "mediator resolving", 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"source of e series", "of e series resolvins", "series resolvins one", "resolvins one of", "one of the specialized", "of the specialized proresolving", "the specialized proresolving mediators", "proresolving mediators spms", "spms that show", "that show potent anti", "show potent anti inflammatory", "potent anti inflammatory and", "anti inflammatory and pro", "inflammatory and pro resolving", "and pro resolving actions", "resolving actions molfino", "actions molfino et", "molfino et al. 2017", "al. 2017 calder", "2017 calder 2017", "calder 2017 . the", "2017 . the initial", ". the initial transformation", "the initial transformation of", "initial transformation of epa", "transformation of epa can", "of epa can be", "epa can be mediated", "can be mediated by", "be mediated by either", "mediated by either cytochrome", "by either cytochrome p450s", "either cytochrome p450s and/or", "cytochrome p450s and/or aspirin", "p450s and/or aspirin acetylated", "and/or aspirin acetylated cyclooxygenase", "aspirin acetylated cyclooxygenase 2", "cyclooxygenase 2 resulting", "2 resulting in", "resulting in stereospecific formation", "in stereospecific formation of", "stereospecific formation of 18", "formation of 18 r", "r and", "18 s e", "s e resolvins.", "e resolvins. combinations of", "resolvins. combinations of oxidation", "of oxidation reduction", "oxidation reduction and", "reduction and hydrolysis reactions", "and hydrolysis reactions determine", "hydrolysis reactions determine the", "reactions determine the type", "determine the type of", "the type of e", "type of e resolvin", "of e resolvin formed", "resolvin formed rve1", "rve1 rve2 or", "rve3 serhan", "serhan & petasis 2011", "& petasis 2011 .", "2011 . aspirin", ". aspirin acetylation", "aspirin acetylation of cyclooxygenase", "acetylation of cyclooxygenase isoforms", "of cyclooxygenase isoforms results", "cyclooxygenase isoforms results in", "isoforms results in changed", "results in changed activities.", "in changed activities. acetylation", "changed activities. acetylation of", "activities. acetylation of cyclooxygenase", "acetylation of cyclooxygenase 1", "of cyclooxygenase 1 results", "cyclooxygenase 1 results in", "1 results in its", "results in its inhibition", "in its inhibition and", "its inhibition and thereby", "inhibition and thereby halting", "and thereby halting production", "thereby halting production of", "halting production of inflammatory", "production of inflammatory mediators.", "of inflammatory mediators. however", "mediators. however acetylation", "however acetylation of", "acetylation of cyclooxygenase 2", "of cyclooxygenase 2 transforms", "cyclooxygenase 2 transforms its", "2 transforms its enzyme", "transforms its enzyme activity", "its enzyme activity from", "enzyme activity from a", "activity from a cyclooxygenase", "from a cyclooxygenase to", "a cyclooxygenase to a", "cyclooxygenase to a lipoxygenase", "a lipoxygenase thereby", "lipoxygenase thereby blocking", "thereby blocking prostaglandin biosynthesis", "blocking prostaglandin biosynthesis and", "biosynthesis and additionally", "additionally initiating the", "initiating the production of", "the production of spms", "of spms arita", "spms arita et", "arita et al. 2005", "al. 2005 kyriakopoulos", "2005 kyriakopoulos et", "kyriakopoulos et al. 2017", "et al. 2017 .", "al. 2017 . the", "2017 . the biosynthesis", ". the biosynthesis of", "the biosynthesis of 18", "biosynthesis of 18 s", "s e resolvins", "e resolvins is described", "resolvins is described here.", "epa a major", "a major \u03c9 3 polyunsaturated", "major \u03c9 3 polyunsaturated fatty", "\u03c9 3 polyunsaturated fatty acid", "polyunsaturated fatty acid pufa", "acid pufa found", "pufa found in fish", "found in fish oil is", "in fish oil is the", "fish oil is the source", "oil is the source of", "is the source of e", "the source of e series", "source of e series resolvins", "e series resolvins one", "series resolvins one of", "resolvins one of the", "one of the specialized proresolving", "of the specialized proresolving mediators", "specialized proresolving mediators spms", "mediators spms that", "spms that show potent", "that show potent anti inflammatory", "show potent anti inflammatory and", "potent anti inflammatory and pro", "anti inflammatory and pro resolving", "inflammatory and pro resolving actions", "pro resolving actions molfino", "resolving actions molfino et", "actions molfino et al.", "et al. 2017 calder", "al. 2017 calder 2017", "2017 calder 2017 .", "calder 2017 . the initial", "2017 . the initial transformation", ". the initial transformation of", "the initial transformation of epa", "initial transformation of epa can", "transformation of epa can be", "of epa can be mediated", "epa can be mediated by", "can be mediated by either", "be mediated by either cytochrome", "mediated by either cytochrome p450s", "by either cytochrome p450s and/or", "either cytochrome p450s and/or aspirin", "cytochrome p450s and/or aspirin acetylated", "p450s and/or aspirin acetylated cyclooxygenase", "and/or aspirin acetylated cyclooxygenase 2", "acetylated cyclooxygenase 2 resulting", "cyclooxygenase 2 resulting in", "2 resulting in stereospecific", "resulting in stereospecific formation of", "in stereospecific formation of 18", "stereospecific formation of 18 r", "18 r and", "r and 18", "and 18 s e", "18 s e resolvins.", "s e resolvins. combinations", "e resolvins. combinations of oxidation", "combinations of oxidation reduction", "of oxidation reduction and", "oxidation reduction and hydrolysis", "reduction and hydrolysis reactions determine", "and hydrolysis reactions determine the", "hydrolysis reactions determine the type", "reactions determine the type of", "determine the type of e", "the type of e resolvin", "type of e resolvin formed", "e resolvin formed rve1", "formed rve1 rve2", "rve1 rve2 or rve3", "or rve3 serhan", "rve3 serhan &", "serhan & petasis 2011 .", "petasis 2011 . aspirin", "2011 . aspirin acetylation", ". aspirin acetylation of", "aspirin acetylation of cyclooxygenase isoforms", "acetylation of cyclooxygenase isoforms results", "of cyclooxygenase isoforms results in", "cyclooxygenase isoforms results in changed", "isoforms results in changed activities.", "results in changed activities. acetylation", "in changed activities. acetylation of", "changed activities. acetylation of cyclooxygenase", "activities. acetylation of cyclooxygenase 1", "acetylation of cyclooxygenase 1 results", "of cyclooxygenase 1 results in", "cyclooxygenase 1 results in its", "1 results in its inhibition", "results in its inhibition and", "in its inhibition and thereby", "its inhibition and thereby halting", "inhibition and thereby halting production", "and thereby halting production of", "thereby halting production of inflammatory", "halting production of inflammatory mediators.", "production of inflammatory mediators. however", "inflammatory mediators. however acetylation", "mediators. however acetylation of", "however acetylation of cyclooxygenase", "acetylation of cyclooxygenase 2 transforms", "of cyclooxygenase 2 transforms its", "cyclooxygenase 2 transforms its enzyme", "2 transforms its enzyme activity", "transforms its enzyme activity from", "its enzyme activity from a", "enzyme activity from a cyclooxygenase", "activity from a cyclooxygenase to", "from a cyclooxygenase to a", "a cyclooxygenase to a lipoxygenase", "to a lipoxygenase thereby", "a lipoxygenase thereby blocking", "lipoxygenase thereby blocking prostaglandin", "thereby blocking prostaglandin biosynthesis and", "prostaglandin biosynthesis and additionally", "and additionally initiating", "additionally initiating the production", "initiating the production of spms", "production of spms arita", "of spms arita et", "spms arita et al.", "et al. 2005 kyriakopoulos", "al. 2005 kyriakopoulos et", "2005 kyriakopoulos et al.", "kyriakopoulos et al. 2017 .", "et al. 2017 . the", "al. 2017 . the biosynthesis", "2017 . the biosynthesis of", ". the biosynthesis of 18", "the biosynthesis of 18 s", "of 18 s e", "18 s e resolvins", "s e resolvins is", "e resolvins is described here." ] }, { "record_id": "GLY_000594_1_1525", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020265", "r hsa", "hsa 9020265", "r hsa 9020265" ] }, { "record_id": "GLY_000594_1_1525", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biosynthesis of", "of aspirin", "aspirin triggered", "triggered d", "d series", "series resolvins", "biosynthesis of aspirin", "of aspirin triggered", "aspirin triggered d", "triggered d series", "d series resolvins", "biosynthesis of aspirin triggered", "of aspirin triggered d", "aspirin triggered d series", "triggered d series resolvins", "biosynthesis of aspirin triggered d", "of aspirin triggered d series", "aspirin triggered d series resolvins", "the d", "rvd1 6", "are 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"catalysis described", "here forming", "forming the epimeric", "the epimeric 17", "epimeric 17 r", "r rvd1", "rvd1 6 resolvins", "resolvins serhan", "serhan et al.", "et al. 2014", "2014 bannenberg", "bannenberg & serhan", "& serhan 2010", "serhan 2010 .", "the d series resolvins", "series resolvins rvd1", "resolvins rvd1 6", "rvd1 6 are", "6 are biosynthesised", "are biosynthesised from the", "biosynthesised from the precursor", "from the precursor \u03c9", "the precursor \u03c9 3", "precursor \u03c9 3 fatty", "\u03c9 3 fatty acid", "3 fatty acid docosahexaenoic", "fatty acid docosahexaenoic acid", "docosahexaenoic acid dha", "dha either", "either via the lipoxygenase", "via the lipoxygenase pathway", "lipoxygenase pathway 17", "pathway 17 s", "17 s rvds", "rvds or via", "or via aspirin triggered", "via aspirin triggered cylcooxygenase", "aspirin triggered cylcooxygenase catalysis", "cylcooxygenase catalysis described", "catalysis described here", "described here forming", "here 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forming the", "here forming the epimeric", "forming the epimeric 17 r", "epimeric 17 r rvd1", "17 r rvd1 6", "r rvd1 6 resolvins", "rvd1 6 resolvins serhan", "6 resolvins serhan et", "resolvins serhan et al.", "et al. 2014 bannenberg", "al. 2014 bannenberg &", "2014 bannenberg & serhan", "bannenberg & serhan 2010 ." ] }, { "record_id": "GLY_000594_1_1526", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9020958", "r hsa", "hsa 9020958", "r hsa 9020958" ] }, { "record_id": "GLY_000594_1_1526", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 21", "21 signaling", "interleukin 21 signaling", "is a", "a pleiotropic", "pleiotropic cytokine", "cytokine with", "with four", "four alpha", "alpha helical", "helical bundles.", "bundles. it", "it is", "is produced", "produced primarily", "primarily by", "by natural", "natural killer", "killer t", "t cells", "t follicular", "follicular helper", "helper cells", "cells and", "and th17", "th17 cells", "with lower", "lower levels", "levels of", "of production", "production by", "by numerous", "numerous other", "other populations", "populations of", "of lymphohaematopoietic", "lymphohaematopoietic cells", "spolski &", "& leonard", "leonard 2014", "2014 .", ". il21", "il21 binds", "binds interleukin", "21 receptor", "and cytokine", "cytokine receptor", "receptor common", "common subunit", "subunit gamma", "gammac .
              il21r", ".
              il21r has", "has significant", "significant homology", "homology with", "with the", "the class", "class i", "i cytokine", "cytokine receptors", "receptors interleukin", "interleukin 2", "2 receptor", "receptor subunit", "subunit beta", "and interleukin", "interleukin 4", "4 receptor", "subunit alpha", "and was", "was predicted", "predicted to", "to similarly", "similarly form", "form a", "a complex", "complex with", "with il2rg.", "il2rg. il21r", "il21r dimers", "dimers can", "can weakly", "weakly bind", "bind and", "and signal", "signal in", "in response", "response to", "to il21", "il21 but", "but il21", "il21 generates", "generates a", "a much", "much stronger", "stronger response", "response when", "when il21r", "il21r is", "is combined", "combined with", "with il2rg", "which is", "is required", "required for", "for a", "a fully", "fully signaling", "signaling capable", "capable il21", "il21 receptor", "receptor complex", "ozaki et", "et al.", "al. 2000", "asao et", "al. 2001", "habib et", "al. 2002", "2002 .", ". il21r", "il21r can", "can bind", "bind janus", "janus kinase", "kinase 1", "but il2rg", "il2rg is", "for il21", "il21 induced", "induced signaling", "2001 .", ". the", "the heteromeric", "heteromeric il21", "complex can", "can activate", "activate jak1", "signal transducer", "transducer and", "and activator", "activator of", "of transcription", "transcription 1", "stat4 and", "and stat5", "depending on", "on the", "the cell", "cell type.", "type. in", "in cultured", "cultured t", "cells il21", "induced phosphorylation", "phosphorylation of", "of jak1", "stat3 and", "and weakly", "weakly stat5", ". in", "in primary", "primary cd4+", "cd4+ t", "induced the", "the phosphorylation", "of stat1", "stat1 and", "and stat3", "stat3 but", "but not", "not stat5", "whereas il2", "il2 induced", "of stat5", "stat5 and", "and stat1", "stat1 but", "not sta3", "bennet et", "al. 2003", "2003 .", "il21 stimulation", "stimulation of", "of primary", "primary splenic", "splenic b", "b cells", "and the", "the pro", "pro b", "b cell", "cell line", "line ba", "ba f3", "f3 induced", "the activation", "activation of", "jak3 and", "primary human", "human nk", "nk cells", "cells or", "or the", "the nk", "nk cell", "line nk", "nk 92", "and stat4", "stat4 but", "strengell et", "il21 activated", "activated stat1", "stat3 in", "in human", "human monocyte", "monocyte derived", "derived macrophages", "valli\u00e8res &", "& girard", "girard 2017", "2017 .", "21 il21", "il21 is", "is a pleiotropic", "a pleiotropic cytokine", "pleiotropic cytokine with", "cytokine with four", "with four alpha", "four alpha helical", "alpha helical bundles.", "helical bundles. it", "bundles. it is", "it is produced", "is produced primarily", "produced primarily by", "primarily by natural", "by natural killer", "natural killer t", "killer t cells", "cells t", "t follicular helper", "follicular helper cells", "helper cells and", "cells and th17", "and th17 cells", "cells with", "with lower levels", "lower levels of", "levels of production", "of production by", "production by numerous", "by numerous other", "numerous other populations", "other populations of", "populations of lymphohaematopoietic", "of lymphohaematopoietic cells", "cells spolski", "spolski & leonard", "& leonard 2014", "leonard 2014 .", "2014 . il21", ". il21 binds", "il21 binds interleukin", "binds interleukin 21", "interleukin 21 receptor", "receptor il21r", "il21r nilr", "nilr and", "and cytokine receptor", "cytokine receptor common", "receptor common subunit", "common subunit gamma", "gamma il2rg", "il2rg gammac", "gammac .
              il21r has", ".
              il21r has significant", "has significant homology", "significant homology with", "homology with the", "with the class", "the class i", "class i cytokine", "i cytokine receptors", "cytokine receptors interleukin", "receptors interleukin 2", "interleukin 2 receptor", "2 receptor subunit", "receptor subunit beta", "beta il2rb", "il2rb and", "and interleukin 4", "interleukin 4 receptor", "4 receptor subunit", "receptor subunit alpha", "alpha il4r", "il4r and", "and was predicted", "was predicted to", "predicted to similarly", "to similarly form", "similarly form a", "form a complex", "a complex with", "complex with il2rg.", "with il2rg. il21r", "il2rg. il21r dimers", "il21r dimers can", "dimers can weakly", "can weakly bind", "weakly bind and", "bind and signal", "and signal in", "signal in response", "in response to", "response to il21", "to il21 but", "il21 but il21", "but il21 generates", "il21 generates a", "generates a much", "a much stronger", "much stronger response", "stronger response when", "response when il21r", "when il21r is", "il21r is combined", "is combined with", "combined with il2rg", "il2rg which", "which is required", "is required for", "required for a", "for a fully", "a fully signaling", "fully signaling capable", "signaling capable il21", "capable il21 receptor", "il21 receptor complex", "complex ozaki", "ozaki et al.", "et al. 2000", "2000 asao", "asao et al.", "et al. 2001", "2001 habib", "habib et al.", "et al. 2002", "al. 2002 .", "2002 . il21r", ". il21r can", "il21r can bind", "can bind janus", "bind janus kinase", "janus kinase 1", "1 jak1", "2000 but", "but il2rg is", "il2rg is required", "required for il21", "for il21 induced", "il21 induced signaling", "signaling asao", "al. 2001 .", "2001 . the", ". the heteromeric", "the heteromeric il21", "heteromeric il21 receptor", "receptor complex can", "complex can activate", "can activate jak1", "jak1 jak3", "jak3 signal", "signal transducer and", "transducer and activator", "and activator of", "activator of transcription", "of transcription 1", "1 stat1", "stat3 stat4", "stat4 and stat5", "stat5 depending", "depending on the", "on the cell", "the cell type.", "cell type. in", "type. in cultured", "in cultured t", "cultured t cells", "t cells il21", "cells il21 induced", "il21 induced phosphorylation", "induced phosphorylation of", "phosphorylation of jak1", "jak3 stat1", "stat1 stat3", "stat3 and weakly", "and weakly stat5", "stat5 asao", "2001 . in", ". in primary", "in primary cd4+", "primary cd4+ t", "cd4+ t cells", "il21 induced the", "induced the phosphorylation", "the phosphorylation of", "phosphorylation of stat1", "of stat1 and", "stat1 and stat3", "and stat3 but", "stat3 but not", "but not stat5", "stat5 whereas", "whereas il2 induced", "il2 induced the", "phosphorylation of stat5", "of stat5 and", "stat5 and stat1", "and stat1 but", "stat1 but not", "but not sta3", "sta3 bennet", "bennet et al.", "et al. 2003", "al. 2003 .", "2003 . il21", ". il21 stimulation", "il21 stimulation of", "stimulation of primary", "of primary splenic", "primary splenic b", "splenic b cells", "b cells and", "cells and the", "and the pro", "the pro b", "pro b cell", "b cell line", "cell line ba", "line ba f3", "ba f3 induced", "f3 induced the", "induced the activation", "the activation of", "activation of jak1", "jak3 and stat5", "stat5 habib", "2002 . in", "in primary human", "primary human nk", "human nk cells", "nk cells or", "cells or the", "or the nk", "the nk cell", "nk cell line", "cell line nk", "line nk 92", "92 il21", "activation of stat1", "and stat4 but", "stat4 but not", "stat5 strengell", "strengell et al.", "2002 2003", ". il21 activated", "il21 activated stat1", "activated stat1 and", "and stat3 in", "stat3 in human", "in human monocyte", "human monocyte derived", "monocyte derived macrophages", "macrophages valli\u00e8res", "valli\u00e8res & girard", "& girard 2017", "girard 2017 .", "interleukin 21 il21", "il21 is a", "is a pleiotropic cytokine", "a pleiotropic cytokine with", "pleiotropic cytokine with four", "cytokine with four alpha", "with four alpha helical", "four alpha helical bundles.", "alpha helical bundles. it", "helical bundles. it is", "bundles. it is produced", "it is produced primarily", "is produced primarily by", "produced primarily by natural", "primarily by natural killer", "by natural killer t", "natural killer t cells", "t cells t", "cells t follicular", "t follicular helper cells", "follicular helper cells and", "helper cells and th17", "cells and th17 cells", "th17 cells with", "cells with lower", "with lower levels of", "lower levels of production", "levels of production by", "of production by numerous", "production by numerous other", "by numerous other populations", "numerous other populations of", "other populations of lymphohaematopoietic", "populations of lymphohaematopoietic cells", "lymphohaematopoietic cells spolski", "cells spolski &", "spolski & leonard 2014", "& leonard 2014 .", "leonard 2014 . il21", "2014 . il21 binds", ". il21 binds interleukin", "il21 binds interleukin 21", "binds interleukin 21 receptor", "21 receptor il21r", "nilr and cytokine", "and cytokine receptor common", "cytokine receptor common subunit", "receptor common subunit gamma", "subunit gamma il2rg", "il2rg gammac .
              il21r", "gammac .
              il21r has significant", ".
              il21r has significant homology", "has significant homology with", "significant homology with the", "homology with the class", "with the class i", "the class i cytokine", "class i cytokine receptors", "i cytokine receptors interleukin", "cytokine receptors interleukin 2", "receptors interleukin 2 receptor", "interleukin 2 receptor subunit", "2 receptor subunit beta", "subunit beta il2rb", "il2rb and interleukin", "and interleukin 4 receptor", "interleukin 4 receptor subunit", "4 receptor subunit alpha", "subunit alpha il4r", "il4r and was", "and was predicted to", "was predicted to similarly", "predicted to similarly form", "to similarly form a", "similarly form a complex", "form a complex with", "a complex with il2rg.", "complex with il2rg. il21r", "with il2rg. il21r dimers", "il2rg. il21r dimers can", "il21r dimers can weakly", "dimers can weakly bind", "can weakly bind and", "weakly bind and signal", "bind and signal in", "and signal in response", "signal in response to", "in response to il21", "response to il21 but", "to il21 but il21", "il21 but il21 generates", "but il21 generates a", "il21 generates a much", "generates a much stronger", "a much stronger response", "much stronger response when", "stronger response when il21r", "response when il21r is", "when il21r is combined", "il21r is combined with", "is combined with il2rg", "with il2rg which", "il2rg which is", "which is required for", "is required for a", "required for a fully", "for a fully signaling", "a fully signaling capable", "fully signaling capable il21", "signaling capable il21 receptor", "capable il21 receptor complex", "receptor complex ozaki", "complex ozaki et", "ozaki et al. 2000", "al. 2000 asao", "2000 asao et", "asao et al. 2001", "al. 2001 habib", "2001 habib et", "habib et al. 2002", "et al. 2002 .", "al. 2002 . il21r", "2002 . il21r can", ". il21r can bind", "il21r can bind janus", "can bind janus kinase", "bind janus kinase 1", "kinase 1 jak1", "jak1 ozaki", "al. 2000 but", "2000 but il2rg", "but il2rg is required", "il2rg is required for", "is required for il21", "required for il21 induced", "for il21 induced signaling", "induced signaling asao", "signaling asao et", "et al. 2001 .", "al. 2001 . the", "2001 . the heteromeric", ". the heteromeric il21", "the heteromeric il21 receptor", "heteromeric il21 receptor complex", "il21 receptor complex can", "receptor complex can activate", "complex can activate jak1", "activate jak1 jak3", "jak3 signal transducer", "signal transducer and activator", "transducer and activator of", "and activator of transcription", "activator of transcription 1", "transcription 1 stat1", "stat3 stat4 and", "and stat5 depending", "stat5 depending on", "depending on the cell", "on the cell type.", "the cell type. in", "cell type. in cultured", "type. in cultured t", "in cultured t cells", "cultured t cells il21", "t cells il21 induced", "cells il21 induced phosphorylation", "il21 induced phosphorylation of", "induced phosphorylation of jak1", "of jak1 jak3", "stat1 stat3 and", "stat3 and weakly stat5", "weakly stat5 asao", "stat5 asao et", "al. 2001 . in", "2001 . in primary", ". in primary cd4+", "in primary cd4+ t", "primary cd4+ t cells", "cd4+ t cells il21", "cells il21 induced the", "il21 induced the phosphorylation", "induced the phosphorylation of", "the phosphorylation of stat1", "phosphorylation of stat1 and", "of stat1 and stat3", "stat1 and stat3 but", "and stat3 but not", "stat3 but not stat5", "not stat5 whereas", "stat5 whereas il2", "whereas il2 induced the", "il2 induced the phosphorylation", "the phosphorylation of stat5", "phosphorylation of stat5 and", "of stat5 and stat1", "stat5 and stat1 but", "and stat1 but not", "stat1 but not sta3", "not sta3 bennet", "sta3 bennet et", "bennet et al. 2003", "et al. 2003 .", "al. 2003 . il21", "2003 . il21 stimulation", ". il21 stimulation of", "il21 stimulation of primary", "stimulation of primary splenic", "of primary splenic b", "primary splenic b cells", "splenic b cells and", "b cells and the", "cells and the pro", "and the pro b", "the pro b cell", "pro b cell line", "b cell line ba", "cell line ba f3", "line ba f3 induced", "ba f3 induced the", "f3 induced the activation", "induced the activation of", "the activation of jak1", "jak1 jak3 and", "and stat5 habib", "stat5 habib et", "al. 2002 . in", "2002 . in primary", ". in primary human", "in primary human nk", "primary human nk cells", "human nk cells or", "nk cells or the", "cells or the nk", "or the nk cell", "the nk cell line", "nk cell line nk", "cell line nk 92", "nk 92 il21", "92 il21 induced", "il21 induced the activation", "the activation of stat1", "of stat1 stat3", "stat3 and stat4", "and stat4 but not", "stat4 but not stat5", "not stat5 strengell", "stat5 strengell et", "strengell et al. 2002", "al. 2002 2003", "2002 2003 .", "2003 . il21 activated", ". il21 activated stat1", "il21 activated stat1 and", "activated stat1 and stat3", "stat1 and stat3 in", "and stat3 in human", "stat3 in human monocyte", "in human monocyte derived", "human monocyte derived macrophages", "derived macrophages valli\u00e8res", "macrophages valli\u00e8res &", "valli\u00e8res & girard 2017", "& girard 2017 .", "21 il21 is", "il21 is a pleiotropic", "is a pleiotropic cytokine with", "a pleiotropic cytokine with four", "pleiotropic cytokine with four alpha", "cytokine with four alpha helical", "with four alpha helical bundles.", "four alpha helical bundles. it", "alpha helical bundles. it is", "helical bundles. it is produced", "bundles. it is produced primarily", "it is produced primarily by", "is produced primarily by natural", "produced primarily by natural killer", "primarily by natural killer t", "by natural killer t cells", "killer t cells t", "t cells t follicular", "cells t follicular helper", "t follicular helper cells and", "follicular helper cells and th17", "helper cells and th17 cells", "and th17 cells with", "th17 cells with lower", "cells with lower levels", "with lower levels of production", "lower levels of production by", "levels of production by numerous", "of production by numerous other", "production by numerous other populations", "by numerous other populations of", "numerous other populations of lymphohaematopoietic", "other populations of lymphohaematopoietic cells", "of lymphohaematopoietic cells spolski", "lymphohaematopoietic cells spolski &", "cells spolski & leonard", "spolski & leonard 2014 .", "& leonard 2014 . il21", "leonard 2014 . il21 binds", "2014 . il21 binds interleukin", ". il21 binds interleukin 21", "il21 binds interleukin 21 receptor", "interleukin 21 receptor il21r", "receptor il21r nilr", "il21r nilr and", "nilr and cytokine receptor", "and cytokine receptor common subunit", "cytokine receptor common subunit gamma", "common subunit gamma il2rg", "gamma il2rg gammac", "il2rg gammac .
              il21r has", "gammac .
              il21r has significant homology", ".
              il21r has significant homology with", "has significant homology with the", "significant homology with the class", "homology with the class i", "with the class i cytokine", "the class i cytokine receptors", "class i cytokine receptors interleukin", "i cytokine receptors interleukin 2", "cytokine receptors interleukin 2 receptor", "receptors interleukin 2 receptor subunit", "interleukin 2 receptor subunit beta", "receptor subunit beta il2rb", "beta il2rb and", "il2rb and interleukin 4", "and interleukin 4 receptor subunit", "interleukin 4 receptor subunit alpha", "receptor subunit alpha il4r", "alpha il4r and", "il4r and was predicted", "and was predicted to similarly", "was predicted to similarly form", "predicted to similarly form a", "to similarly form a complex", "similarly form a complex with", "form a complex with il2rg.", "a complex with il2rg. il21r", "complex with il2rg. il21r dimers", "with il2rg. il21r dimers can", "il2rg. il21r dimers can weakly", "il21r dimers can weakly bind", "dimers can weakly bind and", "can weakly bind and signal", "weakly bind and signal in", "bind and signal in response", "and signal in response to", "signal in response to il21", "in response to il21 but", "response to il21 but il21", "to il21 but il21 generates", "il21 but il21 generates a", "but il21 generates a much", "il21 generates a much stronger", "generates a much stronger response", "a much stronger response when", "much stronger response when il21r", "stronger response when il21r is", "response when il21r is combined", "when il21r is combined with", "il21r is combined with il2rg", "combined with il2rg which", "with il2rg which is", "il2rg which is required", "which is required for a", "is required for a fully", "required for a fully signaling", "for a fully signaling capable", "a fully signaling capable il21", "fully signaling capable il21 receptor", "signaling capable il21 receptor complex", "il21 receptor complex ozaki", "receptor complex ozaki et", "complex ozaki et al.", "et al. 2000 asao", "al. 2000 asao et", "2000 asao et al.", "et al. 2001 habib", "al. 2001 habib et", "2001 habib et al.", "habib et al. 2002 .", "et al. 2002 . il21r", "al. 2002 . il21r can", "2002 . il21r can bind", ". il21r can bind janus", "il21r can bind janus kinase", "can bind janus kinase 1", "janus kinase 1 jak1", "jak1 ozaki et", "et al. 2000 but", "al. 2000 but il2rg", "2000 but il2rg is", "but il2rg is required for", "il2rg is required for il21", "is required for il21 induced", "required for il21 induced signaling", "il21 induced signaling asao", "induced signaling asao et", "signaling asao et al.", "asao et al. 2001 .", "et al. 2001 . the", "al. 2001 . the heteromeric", "2001 . the heteromeric il21", ". the heteromeric il21 receptor", "the heteromeric il21 receptor complex", "heteromeric il21 receptor complex can", "il21 receptor complex can activate", "receptor complex can activate jak1", "can activate jak1 jak3", "jak1 jak3 signal", "jak3 signal transducer and", "signal transducer and activator of", "transducer and activator of transcription", "and activator of transcription 1", "of transcription 1 stat1", "stat3 stat4 and stat5", "stat4 and stat5 depending", "and stat5 depending on", "stat5 depending on the", "depending on the cell type.", "on the cell type. in", "the cell type. in cultured", "cell type. in cultured t", "type. in cultured t cells", "in cultured t cells il21", "cultured t cells il21 induced", "t cells il21 induced phosphorylation", "cells il21 induced phosphorylation of", "il21 induced phosphorylation of jak1", "phosphorylation of jak1 jak3", "jak1 jak3 stat1", "jak3 stat1 stat3", "stat1 stat3 and weakly", "and weakly stat5 asao", "weakly stat5 asao et", "stat5 asao et al.", "et al. 2001 . in", "al. 2001 . in primary", "2001 . in primary cd4+", ". in primary cd4+ t", "in primary cd4+ t cells", "primary cd4+ t cells il21", "cd4+ t cells il21 induced", "t cells il21 induced the", "cells il21 induced the phosphorylation", "il21 induced the phosphorylation of", "induced the phosphorylation of stat1", "the phosphorylation of stat1 and", "phosphorylation of stat1 and stat3", "of stat1 and stat3 but", "stat1 and stat3 but not", "and stat3 but not stat5", "but not stat5 whereas", "not stat5 whereas il2", "stat5 whereas il2 induced", "whereas il2 induced the phosphorylation", "il2 induced the phosphorylation of", "induced the phosphorylation of stat5", "the phosphorylation of stat5 and", "phosphorylation of stat5 and stat1", "of stat5 and stat1 but", "stat5 and stat1 but not", "and stat1 but not sta3", "but not sta3 bennet", "not sta3 bennet et", "sta3 bennet et al.", "bennet et al. 2003 .", "et al. 2003 . il21", "al. 2003 . il21 stimulation", "2003 . il21 stimulation of", ". il21 stimulation of primary", "il21 stimulation of primary splenic", "stimulation of primary splenic b", "of primary splenic b cells", "primary splenic b cells and", "splenic b cells and the", "b cells and the pro", "cells and the pro b", "and the pro b cell", "the pro b cell line", "pro b cell line ba", "b cell line ba f3", "cell line ba f3 induced", "line ba f3 induced the", "ba f3 induced the activation", "f3 induced the activation of", "induced the activation of jak1", "activation of jak1 jak3", "of jak1 jak3 and", "jak1 jak3 and stat5", "jak3 and stat5 habib", "and stat5 habib et", "stat5 habib et al.", "et al. 2002 . in", "al. 2002 . in primary", "2002 . in primary human", ". in primary human nk", "in primary human nk cells", "primary human nk cells or", "human nk cells or the", "nk cells or the nk", "cells or the nk cell", "or the nk cell line", "the nk cell line nk", "nk cell line nk 92", "line nk 92 il21", "nk 92 il21 induced", "92 il21 induced the", "il21 induced the activation of", "induced the activation of stat1", "activation of stat1 stat3", "stat3 and stat4 but", "and stat4 but not stat5", "but not stat5 strengell", "not stat5 strengell et", "stat5 strengell et al.", "et al. 2002 2003", "al. 2002 2003 .", "2002 2003 . il21", "2003 . il21 activated stat1", ". il21 activated stat1 and", "il21 activated stat1 and stat3", "activated stat1 and stat3 in", "stat1 and stat3 in human", "and stat3 in human monocyte", "stat3 in human monocyte derived", "in human monocyte derived macrophages", "monocyte derived macrophages valli\u00e8res", "derived macrophages valli\u00e8res &", "macrophages valli\u00e8res & girard", "valli\u00e8res & girard 2017 ." ] }, { "record_id": "GLY_000594_1_1527", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9022535", "r hsa", "hsa 9022535", "r hsa 9022535" ] }, { "record_id": "GLY_000594_1_1527", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "loss of", "of phosphorylation", "phosphorylation of", "of mecp2", "mecp2 at", "at t308", "loss of phosphorylation", "of phosphorylation of", "phosphorylation of mecp2", "of mecp2 at", "mecp2 at t308", "loss of 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phosphorylation site can negatively", "phosphorylation site can negatively affect", "site can negatively affect the", "can negatively affect the ability", "negatively affect the ability of", "affect the ability of mecp2", "the ability of mecp2 to", "ability of mecp2 to be", "of mecp2 to be phosphorylated", "mecp2 to be phosphorylated at", "to be phosphorylated at t308", "be phosphorylated at t308 in", "phosphorylated at t308 in response", "at t308 in response to", "t308 in response to neuronal", "in response to neuronal membrane", "response to neuronal membrane depolarization", "neuronal membrane depolarization neuronal", "membrane depolarization neuronal activity", "neuronal activity ebert", "activity ebert et", "ebert et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1528", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9022699", "r hsa", "hsa 9022699", "r hsa 9022699" ] }, { "record_id": "GLY_000594_1_1528", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mecp2 regulates", "regulates neuronal", "neuronal receptors", "receptors and", "and channels", "mecp2 regulates neuronal", "regulates neuronal receptors", "neuronal receptors and", "receptors and channels", "mecp2 regulates neuronal receptors", "regulates neuronal receptors and", "neuronal receptors and channels", "mecp2 regulates neuronal receptors and", "regulates neuronal receptors and channels", "receptors directly", "directly transcriptionally", "transcriptionally regulated", "regulated by", "by mecp2", "mecp2 include", "include glutamate", "glutamate receptor", "receptor gria2", "qiu et", "et al.", "al. 2012", "nmda receptor", "receptor subunits", "subunits grin2a", "durand et", "and grin2b", "lee et", "al. 2008", "opioid receptors", "receptors oprk1", "chahrour et", "and oprm1", "hwang et", "al. 2009", "al. 2010", "samaco et", "plummer et", "al. 2013", "and notch1", "li et", "al. 2014", "2014 .", ". channels/transporters", "channels/transporters regulated", "include trpc3", "and slc2a3", "chen et", "2013 .", ". mecp2", "mecp2 also", "also regulates", "regulates transcription", "transcription of", "of fkbp5", "involved in", "in trafficking", "trafficking of", "of glucocorticoid", "glucocorticoid receptors", "nuber et", "al. 2005", "urdinguio et", "and is", "is implicated", "implicated in", "in regulation", "regulation of", "of expression", "expression of", "of sema3f", "semaphorin 3f", "in mouse", "mouse olfactory", "olfactory neurons", "degano et", "2009 .", ". in", "in zebrafish", "mecp2 is", "in sensory", "sensory axon", "axon guidance", "guidance by", "by direct", "direct stimulation", "stimulation of", "of transcription", "of sema5b", "sema5b and", "and robo2", "leong et", "al. 2015", "2015 .", "mecp2 may", "may indirectly", "indirectly regulate", "regulate signaling", "signaling by", "by neuronal", "neuronal receptor", "receptor tyrosine", "tyrosine kinases", "kinases by", "by regulating", "regulating transcription", "of protein", "protein tyrosine", "tyrosine phosphatases", "krishnan et", "and ptpn4", "williamson et", "receptors directly transcriptionally", "directly transcriptionally regulated", "transcriptionally regulated by", "regulated by mecp2", "by mecp2 include", "mecp2 include glutamate", "include glutamate receptor", "glutamate receptor gria2", "gria2 qiu", "qiu et al.", "et al. 2012", "nmda receptor subunits", "receptor subunits grin2a", "grin2a durand", "durand et al.", "2012 and", "grin2b lee", "lee et al.", "et al. 2008", "opioid receptors oprk1", "oprk1 chahrour", "chahrour et al.", "2008 and", "oprm1 hwang", "hwang et al.", "et al. 2009", "2009 hwang", "et al. 2010", "2010 samaco", "samaco et al.", "gprin1 chahrour", "met plummer", "plummer et al.", "et al. 2013", "notch1 li", "li et al.", "et al. 2014", "al. 2014 .", "2014 . channels/transporters", ". channels/transporters regulated", "channels/transporters regulated by", "mecp2 include trpc3", "trpc3 li", "slc2a3 chen", "chen et al.", "al. 2013 .", "2013 . mecp2", ". mecp2 also", "mecp2 also regulates", "also regulates transcription", "regulates transcription of", "transcription of fkbp5", "fkbp5 involved", "involved in trafficking", "in trafficking of", "trafficking of glucocorticoid", "of glucocorticoid receptors", "receptors nuber", "nuber et al.", "et al. 2005", "2005 urdinguio", "urdinguio et al.", "and is implicated", "is implicated in", "implicated in regulation", "in regulation of", "regulation of expression", "of expression of", "expression of sema3f", "sema3f semaphorin", "3f in", "in mouse olfactory", "mouse olfactory neurons", "neurons degano", "degano et al.", "al. 2009 .", "2009 . in", ". in zebrafish", "zebrafish mecp2", "mecp2 is implicated", "implicated in sensory", "in sensory axon", "sensory axon guidance", "axon guidance by", "guidance by direct", "by direct stimulation", "direct stimulation of", "stimulation of transcription", "of transcription of", "transcription of sema5b", "of sema5b and", "sema5b and robo2", "robo2 leong", "leong et al.", "et al. 2015", "al. 2015 .", "2015 . mecp2", ". mecp2 may", "mecp2 may indirectly", "may indirectly regulate", "indirectly regulate signaling", "regulate signaling by", "signaling by neuronal", "by neuronal receptor", "neuronal receptor tyrosine", "receptor tyrosine kinases", "tyrosine kinases by", "kinases by regulating", "by regulating transcription", "regulating transcription of", "transcription of protein", "of protein tyrosine", "protein tyrosine phosphatases", "phosphatases ptpn1", "ptpn1 krishnan", "krishnan et al.", "2015 and", "ptpn4 williamson", "williamson et al.", "receptors directly transcriptionally regulated", "directly transcriptionally regulated by", "transcriptionally regulated by mecp2", "regulated by mecp2 include", "by mecp2 include glutamate", "mecp2 include glutamate receptor", "include glutamate receptor gria2", "receptor gria2 qiu", "gria2 qiu et", "qiu et al. 2012", "2012 nmda", "nmda receptor subunits grin2a", "subunits grin2a durand", "grin2a durand et", "durand et al. 2012", "al. 2012 and", "2012 and grin2b", "and grin2b lee", "grin2b lee et", "lee et al. 2008", "2008 opioid", "receptors oprk1 chahrour", "oprk1 chahrour et", "chahrour et al. 2008", "al. 2008 and", "2008 and oprm1", "and oprm1 hwang", "oprm1 hwang et", "hwang et al. 2009", "al. 2009 hwang", "2009 hwang et", "hwang et al. 2010", "al. 2010 samaco", "2010 samaco et", "samaco et al. 2012", "2012 gprin1", "gprin1 chahrour et", "2008 met", "met plummer et", "plummer et al. 2013", "2013 and", "and notch1 li", "notch1 li et", "li et al. 2014", "et al. 2014 .", "al. 2014 . channels/transporters", "2014 . channels/transporters regulated", ". channels/transporters regulated by", "channels/transporters regulated by mecp2", "by mecp2 include trpc3", "include trpc3 li", "trpc3 li et", "li et al. 2012", "2012 and slc2a3", "and slc2a3 chen", "slc2a3 chen et", "chen et al. 2013", "et al. 2013 .", "al. 2013 . mecp2", "2013 . mecp2 also", ". mecp2 also regulates", "mecp2 also regulates transcription", "also regulates transcription of", "regulates transcription of fkbp5", "of fkbp5 involved", "fkbp5 involved in", "involved in trafficking of", "in trafficking of glucocorticoid", "trafficking of glucocorticoid receptors", "glucocorticoid receptors nuber", "receptors nuber et", "nuber et al. 2005", "al. 2005 urdinguio", "2005 urdinguio et", "urdinguio et al. 2008", "2008 and is", "and is implicated in", "is implicated in regulation", "implicated in regulation of", "in regulation of expression", "regulation of expression of", "of expression of sema3f", "of sema3f semaphorin", "sema3f semaphorin 3f", "semaphorin 3f in", "3f in mouse", "in mouse olfactory neurons", "olfactory neurons degano", "neurons degano et", "degano et al. 2009", "et al. 2009 .", "al. 2009 . in", "2009 . in zebrafish", "in zebrafish mecp2", "zebrafish mecp2 is", "mecp2 is implicated in", "is implicated in sensory", "implicated in sensory axon", "in sensory axon guidance", "sensory axon guidance by", "axon guidance by direct", "guidance by direct stimulation", "by direct stimulation of", "direct stimulation of transcription", "stimulation of transcription of", "of transcription of sema5b", "transcription of sema5b and", "of sema5b and robo2", "and robo2 leong", "robo2 leong et", "leong et al. 2015", "et al. 2015 .", "al. 2015 . mecp2", "2015 . mecp2 may", ". mecp2 may indirectly", "mecp2 may indirectly regulate", "may indirectly regulate signaling", "indirectly regulate signaling by", "regulate signaling by neuronal", "signaling by neuronal receptor", "by neuronal receptor tyrosine", "neuronal receptor tyrosine kinases", "receptor tyrosine kinases by", "tyrosine kinases by regulating", "kinases by regulating transcription", "by regulating transcription of", "regulating transcription of protein", "transcription of protein tyrosine", "of protein tyrosine phosphatases", "tyrosine phosphatases ptpn1", "ptpn1 krishnan et", "krishnan et al. 2015", "al. 2015 and", "2015 and ptpn4", "and ptpn4 williamson", "ptpn4 williamson et", "williamson et al. 2015", "receptors directly transcriptionally regulated by", "directly transcriptionally regulated by mecp2", "transcriptionally regulated by mecp2 include", "regulated by mecp2 include glutamate", "by mecp2 include glutamate receptor", "mecp2 include glutamate receptor gria2", "glutamate receptor gria2 qiu", "receptor gria2 qiu et", "gria2 qiu et al.", "al. 2012 nmda", "2012 nmda receptor", "receptor subunits grin2a durand", "subunits grin2a durand et", "grin2a durand et al.", "et al. 2012 and", "al. 2012 and grin2b", "and grin2b lee et", "grin2b lee et al.", "al. 2008 opioid", "2008 opioid receptors", "opioid receptors oprk1 chahrour", "receptors oprk1 chahrour et", "oprk1 chahrour et al.", "et al. 2008 and", "al. 2008 and oprm1", "and oprm1 hwang et", "oprm1 hwang et al.", "et al. 2009 hwang", "al. 2009 hwang et", "2009 hwang et al.", "et al. 2010 samaco", "al. 2010 samaco et", "2010 samaco et al.", "al. 2012 gprin1", "gprin1 chahrour et al.", "al. 2008 met", "met plummer et al.", "al. 2013 and", "2013 and notch1", "and notch1 li et", "notch1 li et al.", "li et al. 2014 .", "et al. 2014 . channels/transporters", "al. 2014 . channels/transporters regulated", "2014 . channels/transporters regulated by", ". channels/transporters regulated by mecp2", "channels/transporters regulated by mecp2 include", "regulated by mecp2 include trpc3", "mecp2 include trpc3 li", "include trpc3 li et", "trpc3 li et al.", "al. 2012 and slc2a3", "and slc2a3 chen et", "slc2a3 chen et al.", "chen et al. 2013 .", "et al. 2013 . mecp2", "al. 2013 . mecp2 also", "2013 . mecp2 also regulates", ". mecp2 also regulates transcription", "mecp2 also regulates transcription of", "also regulates transcription of fkbp5", "transcription of fkbp5 involved", "of fkbp5 involved in", "fkbp5 involved in trafficking", "involved in trafficking of 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to proceed via", "to proceed via a", "proceed via a two", "via a two step", "a two step process", "step process cox2", "process cox2 hydroxylates", "cox2 hydroxylates dpan 3", "hydroxylates dpan 3 to", "dpan 3 to 13", "3 to 13 r", "13 r dpan", "r dpan 3", "dpan 3 which trafficks", "3 which trafficks to", "which trafficks to adjacent", "trafficks to adjacent neutrophils", "to adjacent neutrophils where", "adjacent neutrophils where it", "neutrophils where it is", "where it is lipoxygenated", "it is lipoxygenated by", "is lipoxygenated by 5", "lipoxygenated by 5 lipoxygenase", "by 5 lipoxygenase to", "5 lipoxygenase to rvt1", "lipoxygenase to rvt1 4", "rvt1 4 vik", "4 vik et", "vik et al. 2017", "et al. 2017 .", "neutrophils adherence to the vascular", "adherence to the vascular endothelium", "to the vascular endothelium is", "the vascular endothelium is a", "vascular endothelium is a critical", "endothelium is a critical and", "is a critical and early", "a critical and early event", "critical and early event in", "and early event in the", "early event in the innate", "event in the innate immune", "in the innate immune response", "the innate immune response to", "innate immune response to injury", "immune response to injury or", "response to injury or invading", "to injury or invading pathogens", "or invading pathogens sadik", "invading pathogens sadik et", "pathogens sadik et al.", "sadik et al. 2011 .", "et al. 2011 . studies", "al. 2011 . studies of", "2011 . studies of the", ". studies of the lipid", "studies of the lipid fraction", "of the lipid fraction from", "the lipid fraction from neutrophil", "lipid fraction from neutrophil endothelial", "fraction from neutrophil endothelial cell", "from neutrophil endothelial cell cultures", "neutrophil endothelial cell cultures resulted", "endothelial cell cultures resulted in", "cell cultures resulted in the", "cultures resulted in the discovery", "resulted in the discovery of", "in the discovery of four", "the discovery of four novel", "discovery of four novel specialised", "of four novel specialised proresolving", "four novel specialised proresolving mediators", "specialised proresolving mediators spms", "spms dalli et", "dalli et al. 2015 .", "et al. 2015 . results", "al. 2015 . results from", "2015 . results from lc/ms", ". results from lc/ms ms", "results from lc/ms ms metabololipidomics", "from lc/ms ms metabololipidomics using", "lc/ms ms metabololipidomics using a", "ms metabololipidomics using a chemically", "metabololipidomics using a chemically synthesised", "using a chemically synthesised precursor", "chemically synthesised precursor 13", "synthesised precursor 13 r", "13 r hydroxy dpan", "r hydroxy dpan 3", "hydroxy dpan 3 identified", "dpan 3 identified four", "3 identified four mediators", "identified four mediators generated from", "four mediators generated from this", "mediators generated from this precursor.

              the", "generated from this precursor.

              the polyunsaturated", "from this precursor.

              the polyunsaturated fatty", "this precursor.

              the polyunsaturated fatty acid", "polyunsaturated fatty acid pufa", "acid pufa \u03c9", "pufa \u03c9 3 cis", "\u03c9 3 cis 7 10", "3 cis 7 10 13", "cis 7 10 13 16", "7 10 13 16 19", "10 13 16 19 docosapentaenoic", "13 16 19 docosapentaenoic acid", "19 docosapentaenoic acid dpan", "docosapentaenoic acid dpan 3", "dpan 3 is an", "3 is an intermediate", "is an intermediate in the", "an intermediate in the biosynthesis", "intermediate in the biosynthesis of", "in the biosynthesis of docosahexaenoic", "the biosynthesis of docosahexaenoic acid", "of docosahexaenoic acid dha", "acid dha from", "dha from eicosapentaenoic acid", "from eicosapentaenoic acid epa", "acid epa and", "epa and is also", "and is also a precursor", "is also a precursor for", "also a precursor for the", "a precursor for the production", "precursor for the production of", "for the production of novel", "the production of novel bioactive", "production of novel bioactive mediators.", "of novel bioactive mediators. dpan", "novel bioactive mediators. dpan 3", "bioactive mediators. dpan 3 can", "mediators. dpan 3 can form", "dpan 3 can form this", "3 can form this precursor", "can form this precursor when", "form this precursor when acted", "this precursor when acted upon", "precursor when acted upon by", "when acted upon by cyclooxygenase", "acted upon by cyclooxygenase 2", "by cyclooxygenase 2 cox2", "cyclooxygenase 2 cox2 .", "2 cox2 . thus", "cox2 . thus these novel", ". thus these novel 13", "thus these novel 13 series", "these novel 13 series resolvins", "13 series resolvins rvt1", "series resolvins rvt1 4", "rvt1 4 originate from", "4 originate from dpan", "from dpan 3 primdahl", "dpan 3 primdahl et", "3 primdahl et al.", "primdahl et al. 2016 .", "et al. 2016 . in", "al. 2016 . in e.", "2016 . in e. coli", ". in e. coli infected", "in e. coli infected mice", "coli infected mice rvts", "infected mice rvts accelerated", "mice rvts accelerated resolution", "rvts accelerated resolution of inflammation", "accelerated resolution of inflammation and", "resolution of inflammation and increased", "of inflammation and increased survival.", "inflammation and increased survival. rvts", "and increased survival. rvts also", "increased survival. rvts also regulated", "survival. rvts also regulated human", "rvts also regulated human and", "also regulated human and mouse", "regulated human and mouse phagocyte", "human and mouse phagocyte responses", "mouse phagocyte responses stimulating", "phagocyte responses stimulating bacterial", "responses stimulating bacterial phagocytosis", "stimulating bacterial phagocytosis and regulating", "bacterial phagocytosis and regulating inflammasome", "phagocytosis and regulating inflammasome components", "regulating inflammasome components dalli", "inflammasome components dalli et", "components dalli et al.", "et al. 2015 . the", "al. 2015 . the biosynthetic", "2015 . the biosynthetic routes", ". the biosynthetic routes of", "the biosynthetic routes of these", "biosynthetic routes of these rvts", "routes of these rvts are", "of these rvts are described", "these rvts are described here.", "rvts are described here. rvt", "are described here. rvt formation", "described here. rvt formation requires", "here. rvt formation requires neutrophil", "rvt formation requires neutrophil endothelial", "formation requires neutrophil endothelial cell", "requires neutrophil endothelial cell interaction", "neutrophil endothelial cell interaction and", "endothelial cell interaction and is", "cell interaction and is thought", "interaction and is thought to", "and is thought to proceed", "is thought to proceed via", "thought to proceed via a", "to proceed via a two", "proceed via a two step", "via a two step process", "two step process cox2", "step process cox2 hydroxylates", "process cox2 hydroxylates dpan", "cox2 hydroxylates dpan 3 to", "hydroxylates dpan 3 to 13", "dpan 3 to 13 r", "to 13 r dpan", "13 r dpan 3", "r dpan 3 which", "dpan 3 which trafficks to", "3 which trafficks to adjacent", "which trafficks to adjacent neutrophils", "trafficks to adjacent neutrophils where", "to adjacent neutrophils where it", "adjacent neutrophils where it is", "neutrophils where it is lipoxygenated", "where it is lipoxygenated by", "it is lipoxygenated by 5", "is lipoxygenated by 5 lipoxygenase", "lipoxygenated by 5 lipoxygenase to", "by 5 lipoxygenase to rvt1", "5 lipoxygenase to rvt1 4", "to rvt1 4 vik", "rvt1 4 vik et", "4 vik et al.", "vik et al. 2017 ." ] }, { "record_id": "GLY_000594_1_1537", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9026527", "r hsa", "hsa 9026527", "r hsa 9026527" ] }, { "record_id": "GLY_000594_1_1537", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated ntrk2", "ntrk2 signals", "signals through", "through plcg1", "activated ntrk2 signals", "ntrk2 signals through", "signals through plcg1", 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"et al. 1998 mccarthy", "al. 1998 mccarthy and", "1998 mccarthy and feinstein", "and feinstein 1999 yuen", "feinstein 1999 yuen and", "1999 yuen and mobley", "and mobley 1999 minichiello", "mobley 1999 minichiello et", "1999 minichiello et al.", "et al. 2002 yamada", "al. 2002 yamada et", "2002 yamada et al.", "yamada et al. 2002 ." ] }, { "record_id": "GLY_000594_1_1538", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9027307", "r hsa", "hsa 9027307", "r hsa 9027307" ] }, { "record_id": "GLY_000594_1_1538", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biosynthesis of", "of maresin", "maresin like", "like spms", "biosynthesis of maresin", "of maresin like", "maresin like spms", "biosynthesis of maresin like", "of maresin like spms", "biosynthesis of maresin like spms", "like mediators", "mediators mar", "mar l1", "mar l2", "l2 and", "and 14", "14 21", "21 dihydroxy", "dihydroxy docosahexaenoic", "docosahexaenoic acids", "acids are", "are normally", "normally synthesized", "synthesized by", "by leukocytes", "platelets and", "and macrophages", "via the", "the pathways", "pathways described", "described here.", "here. impaired", "impaired production", "production of", "of these", "these specialised", "specialised proresolving", "proresolving mediators", "in diabetic", "diabetic skin", "skin wounds", "wounds is", "is associated", "associated with", "with impaired", "impaired macrophage", "macrophage function", "function and", "and delayed", "delayed or", "or absent", "absent wound", "wound healing", "brem &", "& tomic", "tomic canic", "canic 2007", "boniakowski et", "et al", "al 2017", "2017 .", ". macrophages", "macrophages play", "play critical", "critical roles", "roles in", "in wound", "healing by", "by mechanisms", "mechanisms as", "as yet", "yet unknown.", "unknown. they", "they are", "are active", "active in", "in both", "both the", "the initiation", "m1 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              administration", ".

              administration of", "spms to", "to diabetic", "diabetic mice", "mice with", "with induced", "induced wounds", "wounds have", "have been", "been shown", "shown to", "to act", "act as", "as autocrine/paracrine", "autocrine/paracrine factors", "factors in", "in restoring", "restoring reparative", "reparative functions", "functions of", "of macrophages", "hong et", "al. 2014", "tian et", "al. 2011a", "lu et", "al. 2010", "hellman et", "al. 2012", "2012 .", "maresin like mediators", "like mediators mar", "mediators mar l1", "l1 mar", "mar l2 and", "l2 and 14", "and 14 21", "14 21 dihydroxy", "21 dihydroxy docosahexaenoic", "dihydroxy docosahexaenoic acids", "docosahexaenoic acids are", "acids are normally", "are normally synthesized", "normally synthesized by", "synthesized by leukocytes", "leukocytes platelets", "platelets and macrophages", "macrophages via", "via the pathways", "the pathways described", "pathways described here.", "described here. impaired", "here. impaired production", "impaired production of", "production of these", "of these specialised", "these specialised proresolving", "specialised proresolving mediators", "mediators spms", "spms in", "in diabetic skin", "diabetic skin wounds", "skin wounds is", "wounds is associated", "is associated with", "associated with impaired", "with impaired macrophage", "impaired macrophage function", "macrophage function and", "function and delayed", "and delayed or", "delayed or absent", "or absent wound", "absent wound healing", "healing brem", "brem & tomic", "& tomic canic", "tomic canic 2007", "2007 boniakowski", "boniakowski et al", "et al 2017", "al 2017 .", "2017 . macrophages", ". macrophages play", "macrophages play critical", "play critical roles", "critical roles in", "roles in wound", "in wound healing", "wound healing by", "healing by mechanisms", "by mechanisms as", "mechanisms as yet", "as yet unknown.", "yet unknown. they", "unknown. they are", "they are active", "are active in", "active in both", "in both the", "both the initiation", "initiation m1", "m1 macrophage phenotype", "phenotype and", "and the resolution", "resolution m2", "m2 macrophage phenotype", "phenotype of", "of inflammatory processes.", "inflammatory processes. in", "processes. in a", "in a pathological", "a pathological state", "state the", "the switch from", "switch from the", "from the m1", "the m1 phenotype", "m1 phenotype macrophage", "phenotype macrophage to", "macrophage to the", "to the m2", "the m2 phenotype", "m2 phenotype macrophage", "phenotype macrophage may", "macrophage may be", "may be delayed", "be delayed or", "delayed or fail", "or fail to", "fail to occur", "occur which", "which can result", "can result in", "result in chronic", "in chronic low", "chronic low grade", "low grade inflammation.", "grade inflammation. this", "inflammation. this macrophage", "this macrophage phenotype", "macrophage phenotype skewing", "phenotype skewing toward", "skewing toward an", "toward an inflammatory", "an inflammatory phenotype", "inflammatory phenotype has", "phenotype has been", "has been implicated", "been implicated in", "implicated in the", "in the pathogenesis", "the pathogenesis of", "pathogenesis of type", "of type 2", "type 2 diabetes", "diabetes t2d", "t2d and", "and the non", "the non healing", "non healing of", "healing of diabetic", "of diabetic wounds", "wounds boniakowski", "2017 pradhan", "pradhan et al.", "et al. 2009", "al. 2009 .

              administration", "2009 .

              administration of", ".

              administration of maresin", "like spms to", "spms to diabetic", "to diabetic mice", "diabetic mice with", "mice with induced", "with induced wounds", "induced wounds have", "wounds have been", "have been shown", "been shown to", "shown to act", "to act as", "act as autocrine/paracrine", "as autocrine/paracrine factors", "autocrine/paracrine factors in", "factors in restoring", "in restoring reparative", "restoring reparative functions", "reparative functions of", "functions of macrophages", "macrophages hong", "hong et al.", "et al. 2014", "2014 tian", "tian et al.", "et al. 2011a", "2011a 2011b", "2011b lu", "lu et al.", "et al. 2010", "2010 hellman", "hellman et al.", "et al. 2012", "al. 2012 .", "maresin like mediators mar", "like mediators mar l1", "mar l1 mar", "l1 mar l2", "mar l2 and 14", "l2 and 14 21", "and 14 21 dihydroxy", "14 21 dihydroxy docosahexaenoic", "21 dihydroxy docosahexaenoic acids", "dihydroxy docosahexaenoic acids are", "docosahexaenoic acids are normally", "acids are normally synthesized", "are normally synthesized by", "normally synthesized by leukocytes", "by leukocytes platelets", "leukocytes platelets and", "and macrophages via", "macrophages via the", "via the pathways described", "the pathways described here.", "pathways described here. impaired", "described here. impaired production", "here. impaired production of", "impaired production of these", "production of these specialised", "of these specialised proresolving", "these specialised proresolving mediators", "proresolving mediators spms", "spms in diabetic", "in diabetic skin wounds", "diabetic skin wounds is", "skin wounds is associated", "wounds is associated with", "is associated with impaired", "associated with impaired macrophage", "with impaired macrophage function", "impaired macrophage function and", "macrophage function and delayed", "function and delayed or", "and delayed or absent", "delayed or absent wound", "or absent wound healing", "wound healing brem", "healing brem &", "brem & tomic canic", "& tomic canic 2007", "canic 2007 boniakowski", "2007 boniakowski et", "boniakowski et al 2017", "et al 2017 .", "al 2017 . macrophages", "2017 . macrophages play", ". macrophages play critical", "macrophages play critical roles", "play critical roles in", "critical roles in wound", "roles in wound healing", "in wound healing by", "wound healing by mechanisms", "healing by mechanisms as", "by mechanisms as yet", "mechanisms as yet unknown.", "as yet unknown. they", "yet unknown. they are", "unknown. they are active", "they are active in", "are active in both", "active in both the", "in both the initiation", "the initiation m1", "initiation m1 macrophage", "macrophage phenotype and", "phenotype and the", "the resolution m2", "resolution m2 macrophage", "macrophage phenotype of", "phenotype of inflammatory", "of inflammatory processes. in", "inflammatory processes. in a", "processes. in a pathological", "in a pathological state", "pathological state the", "state the switch", "the switch from the", "switch from the m1", "from the m1 phenotype", "the m1 phenotype macrophage", "m1 phenotype macrophage to", "phenotype macrophage to the", "macrophage to the m2", "to the m2 phenotype", "the m2 phenotype macrophage", "m2 phenotype macrophage may", "phenotype macrophage may be", "macrophage may be delayed", "may be delayed or", "be delayed or fail", "delayed or fail to", "or fail to occur", "to occur which", "occur which can", "which can result in", "can result in chronic", "result in chronic low", "in chronic low grade", "chronic low grade inflammation.", "low grade inflammation. this", "grade inflammation. this macrophage", "inflammation. this macrophage phenotype", "this macrophage phenotype skewing", "macrophage phenotype skewing toward", "phenotype skewing toward an", "skewing toward an inflammatory", "toward an inflammatory phenotype", "an inflammatory phenotype has", "inflammatory phenotype has been", "phenotype has been implicated", "has been implicated in", "been implicated in the", "implicated in the pathogenesis", "in the pathogenesis of", "the pathogenesis of type", "pathogenesis of type 2", "of type 2 diabetes", "2 diabetes t2d", "t2d and the", "and the non healing", "the non healing of", "non healing of diabetic", "healing of diabetic wounds", "diabetic wounds boniakowski", "wounds boniakowski et", "al 2017 pradhan", "2017 pradhan et", "pradhan et al. 2009", "et al. 2009 .

              administration", "al. 2009 .

              administration of", "2009 .

              administration of maresin", ".

              administration of maresin like", "maresin like spms to", "like spms to diabetic", "spms to diabetic mice", "to diabetic mice with", "diabetic mice with induced", "mice with induced wounds", "with induced wounds have", "induced wounds have been", "wounds have been shown", "have been shown to", "been shown to act", "shown to act as", "to act as autocrine/paracrine", "act as autocrine/paracrine factors", "as autocrine/paracrine factors in", "autocrine/paracrine factors in restoring", "factors in restoring reparative", "in restoring reparative functions", "restoring reparative functions of", "reparative functions of macrophages", "of macrophages hong", "macrophages hong et", "hong et al. 2014", "al. 2014 tian", "2014 tian et", "tian et al. 2011a", "al. 2011a 2011b", "2011b lu et", "lu et al. 2010", "al. 2010 hellman", "2010 hellman et", "hellman et al. 2012", "et al. 2012 .", "maresin like mediators mar l1", "mediators mar l1 mar", "mar l1 mar l2", "l1 mar l2 and", "mar l2 and 14 21", "l2 and 14 21 dihydroxy", "and 14 21 dihydroxy docosahexaenoic", "14 21 dihydroxy docosahexaenoic acids", "21 dihydroxy docosahexaenoic acids are", "dihydroxy docosahexaenoic acids are normally", "docosahexaenoic acids are normally synthesized", "acids are normally synthesized by", "are normally synthesized by leukocytes", "synthesized by leukocytes platelets", "by leukocytes platelets and", "leukocytes platelets and macrophages", "platelets and macrophages via", "and macrophages via the", "macrophages via the pathways", "via the pathways described here.", "the pathways described here. impaired", "pathways described here. impaired production", "described here. impaired production of", "here. impaired production of these", "impaired production of these specialised", "production of these specialised proresolving", "of these specialised proresolving mediators", "specialised proresolving mediators spms", "mediators spms in", "spms in diabetic skin", "in diabetic skin wounds is", "diabetic skin wounds is associated", "skin wounds is associated with", "wounds is associated with impaired", "is associated with impaired macrophage", "associated with impaired macrophage function", "with impaired macrophage function and", "impaired macrophage function and delayed", "macrophage function and delayed or", "function and delayed or absent", "and delayed or absent wound", "delayed or absent wound healing", "absent wound healing brem", "wound healing brem &", "healing brem & tomic", "brem & tomic canic 2007", "tomic canic 2007 boniakowski", "canic 2007 boniakowski et", "2007 boniakowski et al", "boniakowski et al 2017 .", "et al 2017 . macrophages", "al 2017 . macrophages play", "2017 . macrophages play critical", ". macrophages play critical roles", "macrophages play critical roles in", "play critical roles in wound", "critical roles in wound healing", "roles in wound healing by", "in wound healing by mechanisms", "wound healing by mechanisms as", "healing by 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phenotype macrophage to the", "phenotype macrophage to the m2", "macrophage to the m2 phenotype", "to the m2 phenotype macrophage", "the m2 phenotype macrophage may", "m2 phenotype macrophage may be", "phenotype macrophage may be delayed", "macrophage may be delayed or", "may be delayed or fail", "be delayed or fail to", "delayed or fail to occur", "fail to occur which", "to occur which can", "occur which can result", "which can result in chronic", "can result in chronic low", "result in chronic low grade", "in chronic low grade inflammation.", "chronic low grade inflammation. this", "low grade inflammation. this macrophage", "grade inflammation. this macrophage phenotype", "inflammation. this macrophage phenotype skewing", "this macrophage phenotype skewing toward", "macrophage phenotype skewing toward an", "phenotype skewing toward an inflammatory", "skewing toward an inflammatory phenotype", "toward an inflammatory phenotype has", "an inflammatory phenotype has been", "inflammatory phenotype has been implicated", "phenotype has been implicated in", "has been implicated in the", "been implicated in the pathogenesis", "implicated in the pathogenesis of", "in the pathogenesis of type", "the pathogenesis of type 2", "pathogenesis of type 2 diabetes", "type 2 diabetes t2d", "diabetes t2d and", "t2d and the non", "and the non healing of", "the non healing of diabetic", "non healing of diabetic wounds", "of diabetic wounds boniakowski", "diabetic wounds boniakowski et", "wounds boniakowski et al", "et al 2017 pradhan", "al 2017 pradhan et", "2017 pradhan et al.", "pradhan et al. 2009 .

              administration", "et al. 2009 .

              administration of", "al. 2009 .

              administration of maresin", "2009 .

              administration of maresin like", ".

              administration of maresin like spms", "of maresin like spms to", "maresin like spms to diabetic", "like spms to diabetic mice", "spms to diabetic mice with", "to diabetic mice with induced", "diabetic mice with induced wounds", "mice with induced wounds have", "with induced wounds have been", "induced wounds have been shown", "wounds have been shown to", "have been shown to act", "been shown to act as", "shown to act as autocrine/paracrine", "to act as autocrine/paracrine factors", "act as autocrine/paracrine factors in", "as autocrine/paracrine factors in restoring", "autocrine/paracrine factors in restoring reparative", "factors in restoring reparative functions", "in restoring reparative functions of", "restoring reparative functions of macrophages", "functions of macrophages hong", "of macrophages hong et", "macrophages hong et al.", "et al. 2014 tian", "al. 2014 tian et", "2014 tian et al.", "et al. 2011a 2011b", "2011a 2011b lu", "2011b lu et al.", "et al. 2010 hellman", "al. 2010 hellman et", "2010 hellman et al.", "hellman et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1539", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9027604", "r hsa", "hsa 9027604", "r hsa 9027604" ] }, { "record_id": "GLY_000594_1_1539", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "biosynthesis of", "of electrophilic", "electrophilic \u03c9", "\u03c9 3", "3 pufa", "pufa oxo", "oxo derivatives", "biosynthesis of electrophilic", "of electrophilic \u03c9", "electrophilic \u03c9 3", "\u03c9 3 pufa", "3 pufa oxo", "pufa oxo derivatives", "biosynthesis of electrophilic \u03c9", "of electrophilic \u03c9 3", "electrophilic \u03c9 3 pufa", "\u03c9 3 pufa oxo", "3 pufa oxo derivatives", "biosynthesis of electrophilic \u03c9 3", "of electrophilic \u03c9 3 pufa", "electrophilic \u03c9 3 pufa oxo", "\u03c9 3 pufa oxo derivatives", "electrophilic oxo", "derivatives of", "of \u03c9", "3 polyunsaturated", "polyunsaturated fatty", "fatty acids", "3 pufas", "are generated", "generated in", "in macrophages", "macrophages and", "and neutrophils", "neutrophils in", "in response", "response to", "to inflammation", "inflammation and", "and oxidative", "oxidative stress", "stress to", "to promote", "promote the", "the resolution", "resolution of", "of inflammation.", "inflammation. being", "being electrophilic", "these derivatives", "derivatives reversibly", "reversibly bind", "bind to", "to nucleophilic", "nucleophilic residues", "residues on", "on target", "target proteins", "thiolates of", "of cysteines", "cysteines and", "and amino", "amino groups", "groups of", "of histidine", "histidine and", "and lysine", "triggering the", "the activation", "activation of", "of cytoprotective", "cytoprotective pathways.", "pathways. these", "these include", "include the", "the nrf2", "nrf2 antioxidant", "antioxidant response", "the heat", "heat shock", "shock response", "response and", "and the", "the peroxisome", "peroxisome proliferator", "proliferator activated", "activated receptor", "receptor \u03b3", "and suppressing", "suppressing the", "the nf", "nf \u03bab", "\u03bab proinflammatory", "proinflammatory pathway", "cipollina 2015", "2015 .", ". thus", "these electrophilic", "electrophilic derivatives", "derivatives transduce", "transduce anti", "anti inflammatory", "inflammatory actions", "actions rather", "rather than", "than suppress", "suppress the", "the production", "production of", "of pro", "pro inflammatory", "inflammatory arachidonic", "arachidonic acid", "acid metabolites.", "metabolites. an", "an oxo", "oxo derivative", "derivative of", "of epa", "epa has", "has been", "been shown", "shown to", "to ablate", "ablate leukemia", "leukemia stem", "stem cells", "cells in", "in mice", "which may", "may represent", "represent a", "a novel", "novel chemoprotective", "chemoprotective action", "action for", "for some", "some oxo", "hedge et", "et al.", "al. 2011", "finch et", "al. 2015", ". in", "in humans", "dietary supplementation", "supplementation with", "with \u03c9", "pufas has", "been reported", "reported to", "to increase", "increase the", "the formation", "formation of", "of oxo", "yates et", "al. 2014", "2014 .", ". the", "the enzymes", "enzymes cyclooxygenases", "and cytochromes", "cytochromes p450s", "acting alone", "alone or", "or in", "in concerted", "concerted transcellular", "transcellular biosynthesis", "initially form", "form epoxy", "epoxy or", "or hydroxy", "hydroxy intermediates", "intermediates of", "pufas docosahexaenoic", "docosahexaenoic acid", "docosapentaenoic acid", "dpan 3", "and eicosapentaenoic", "eicosapentaenoic acid", "before these", "these are", "are further", "further oxidised", "oxidised to", "to electrophilic", "electrophilic \u03b1", "\u03b1 \u03b2", "\u03b2 unsaturated", "unsaturated keto", "keto derivatives", "derivatives by", "by cellular", "cellular dehydrogenases.", "electrophilic oxo derivatives", "oxo derivatives of", "derivatives of \u03c9", "of \u03c9 3", "\u03c9 3 polyunsaturated", "3 polyunsaturated fatty", "polyunsaturated fatty acids", "acids \u03c9", "\u03c9 3 pufas", "pufas are", "are generated in", "generated in macrophages", "in macrophages and", "macrophages and neutrophils", "and neutrophils in", "neutrophils in response", "in response to", "response to inflammation", "to inflammation and", "inflammation and oxidative", "and oxidative stress", "oxidative stress to", "stress to promote", "to promote the", "promote the resolution", "the resolution of", "resolution of inflammation.", "of inflammation. being", "inflammation. being electrophilic", "electrophilic these", "these derivatives reversibly", "derivatives reversibly bind", "reversibly bind to", "bind to nucleophilic", "to nucleophilic residues", "nucleophilic residues on", "residues on target", "on target proteins", "proteins thiolates", "thiolates of cysteines", "of cysteines and", "cysteines and amino", "and amino groups", "amino groups of", "groups of histidine", "of histidine and", "histidine and lysine", "triggering the activation", "the activation of", "activation of cytoprotective", "of cytoprotective pathways.", "cytoprotective pathways. these", "pathways. these include", "these include the", "include the nrf2", "the nrf2 antioxidant", "nrf2 antioxidant response", "response the", "the heat shock", "heat shock response", "shock response and", "response and the", "and the peroxisome", "the peroxisome proliferator", "peroxisome proliferator activated", "proliferator activated receptor", "activated receptor \u03b3", "\u03b3 ppar\u03b3", "ppar\u03b3 and", "and suppressing the", "suppressing the nf", "the nf \u03bab", "nf \u03bab proinflammatory", "\u03bab proinflammatory pathway", "pathway cipollina", "cipollina 2015 .", "2015 . thus", "thus these", "these electrophilic derivatives", "electrophilic derivatives transduce", "derivatives transduce anti", "transduce anti inflammatory", "anti inflammatory actions", "inflammatory actions rather", "actions rather than", "rather than suppress", "than suppress the", "suppress the production", "the production of", "production of pro", "of pro inflammatory", "pro inflammatory arachidonic", "inflammatory arachidonic acid", "arachidonic acid metabolites.", "acid metabolites. an", "metabolites. an oxo", "an oxo derivative", "oxo derivative of", "derivative of epa", "of epa has", "epa has been", "has been shown", "been shown to", "shown to ablate", "to ablate leukemia", "ablate leukemia stem", "leukemia stem cells", "stem cells in", "cells in mice", "mice which", "which may represent", "may represent a", "represent a novel", "a novel chemoprotective", "novel chemoprotective action", "chemoprotective action for", "action for some", "for some oxo", "some oxo derivatives", "derivatives hedge", "hedge et al.", "et al. 2011", "2011 finch", "finch et al.", "et al. 2015", "al. 2015 .", "2015 . in", ". in humans", "humans dietary", "dietary supplementation with", "supplementation with \u03c9", "with \u03c9 3", "3 pufas has", "pufas has been", "has been reported", "been reported to", "reported to increase", "to increase the", "increase the formation", "the formation of", "formation of oxo", "of oxo derivatives", "derivatives yates", "yates et al.", "et al. 2014", "al. 2014 .", "2014 . the", ". the enzymes", "the enzymes cyclooxygenases", "cyclooxygenases cox", "lipoxygenases los", "los and", "and cytochromes p450s", "p450s acting", "acting alone or", "alone or in", "or in concerted", "in concerted transcellular", "concerted transcellular biosynthesis", "biosynthesis initially", "initially form epoxy", "form epoxy or", "epoxy or hydroxy", "or hydroxy intermediates", "hydroxy intermediates of", "intermediates of \u03c9", "3 pufas docosahexaenoic", "pufas docosahexaenoic acid", "acid dha", "acid dpan", "3 and", "and eicosapentaenoic acid", "acid epa", "epa before", "before these are", "these are 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promote the resolution", "promote the resolution of", "the resolution of inflammation.", "resolution of inflammation. being", "of inflammation. being electrophilic", "being electrophilic these", "electrophilic these derivatives", "these derivatives reversibly bind", "derivatives reversibly bind to", "reversibly bind to nucleophilic", "bind to nucleophilic residues", "to nucleophilic residues on", "nucleophilic residues on target", "residues on target proteins", "target proteins thiolates", "proteins thiolates of", "thiolates of cysteines and", "of cysteines and amino", "cysteines and amino groups", "and amino groups of", "amino groups of histidine", "groups of histidine and", "of histidine and lysine", "lysine triggering", "triggering the activation of", "the activation of cytoprotective", "activation of cytoprotective pathways.", "of cytoprotective pathways. these", "cytoprotective pathways. these include", "pathways. these include the", "these include the nrf2", "include the nrf2 antioxidant", "the nrf2 antioxidant response", "antioxidant response the", "response the heat", "the heat shock response", "heat shock response and", "shock response and the", "response and the peroxisome", "and the peroxisome proliferator", "the peroxisome proliferator activated", "peroxisome proliferator activated receptor", "proliferator activated receptor \u03b3", "receptor \u03b3 ppar\u03b3", "ppar\u03b3 and suppressing", "and suppressing the nf", "suppressing the nf \u03bab", "the nf \u03bab proinflammatory", "nf \u03bab proinflammatory pathway", "proinflammatory pathway cipollina", "pathway cipollina 2015", "cipollina 2015 . thus", ". thus these", "thus these electrophilic", "these electrophilic derivatives transduce", "electrophilic derivatives transduce anti", "derivatives transduce anti inflammatory", "transduce anti inflammatory actions", "anti inflammatory actions rather", "inflammatory actions rather than", "actions rather than suppress", "rather than suppress the", "than suppress the production", "suppress the production of", "the production of pro", "production of pro inflammatory", "of pro inflammatory arachidonic", "pro inflammatory arachidonic acid", "inflammatory arachidonic acid metabolites.", "arachidonic acid metabolites. an", "acid metabolites. an oxo", "metabolites. an oxo derivative", "an oxo derivative of", "oxo derivative of epa", "derivative of epa has", "of epa has been", "epa has been shown", "has been shown to", "been shown to ablate", "shown to ablate leukemia", "to ablate leukemia stem", "ablate leukemia stem cells", "leukemia stem cells in", "stem cells in mice", "in mice which", "mice which may", "which may represent a", "may represent a novel", "represent a novel chemoprotective", "a novel chemoprotective action", "novel chemoprotective action for", "chemoprotective action for some", "action for some oxo", "for some oxo derivatives", "oxo derivatives hedge", "derivatives hedge et", "hedge et al. 2011", "al. 2011 finch", "2011 finch et", "finch et al. 2015", "et al. 2015 .", "al. 2015 . in", "2015 . in humans", "in humans dietary", "humans dietary supplementation", "dietary supplementation with \u03c9", "supplementation with \u03c9 3", "with \u03c9 3 pufas", "\u03c9 3 pufas has", "3 pufas has been", "pufas has been reported", "has been reported to", "been reported to increase", "reported to increase the", "to increase the formation", "increase the formation of", "the formation of oxo", "formation of oxo derivatives", "oxo derivatives yates", "derivatives yates et", "yates et al. 2014", "et al. 2014 .", "al. 2014 . the", "2014 . the enzymes", ". the enzymes cyclooxygenases", "enzymes cyclooxygenases cox", "cox lipoxygenases", "los and cytochromes", "cytochromes p450s acting", "p450s acting alone", "acting alone or in", "alone or in concerted", "or in concerted transcellular", "in concerted transcellular biosynthesis", "transcellular biosynthesis initially", "biosynthesis initially form", "initially form epoxy or", "form epoxy or hydroxy", "epoxy or hydroxy intermediates", "or hydroxy intermediates of", "hydroxy intermediates of \u03c9", "intermediates of \u03c9 3", "of \u03c9 3 pufas", "\u03c9 3 pufas docosahexaenoic", "3 pufas docosahexaenoic acid", "docosahexaenoic acid dha", "dha docosapentaenoic", "docosapentaenoic acid dpan", "acid dpan 3", "dpan 3 and", "3 and eicosapentaenoic", "eicosapentaenoic acid epa", "epa before these", "before these are further", "these are further oxidised", "are further oxidised to", "further oxidised to electrophilic", "oxidised to electrophilic \u03b1", "to electrophilic \u03b1 \u03b2", "electrophilic \u03b1 \u03b2 unsaturated", "\u03b1 \u03b2 unsaturated keto", "\u03b2 unsaturated keto derivatives", "unsaturated keto derivatives by", "keto derivatives by cellular", "derivatives by cellular dehydrogenases.", "electrophilic oxo derivatives of \u03c9", "oxo derivatives of \u03c9 3", "derivatives of \u03c9 3 polyunsaturated", "of \u03c9 3 polyunsaturated fatty", "\u03c9 3 polyunsaturated fatty acids", "polyunsaturated fatty acids \u03c9", "fatty acids \u03c9 3", "acids \u03c9 3 pufas", "\u03c9 3 pufas are", "3 pufas are generated", "pufas are generated in", "are generated in macrophages and", "generated in macrophages and neutrophils", "in macrophages and neutrophils in", "macrophages and neutrophils in response", "and neutrophils in response to", "neutrophils in response to inflammation", "in response to inflammation and", "response to inflammation and oxidative", "to inflammation and oxidative stress", "inflammation and oxidative stress to", "and oxidative stress to promote", "oxidative stress to promote the", "stress to promote the resolution", "to promote the resolution of", "promote the resolution of inflammation.", "the resolution of inflammation. being", "resolution of inflammation. being electrophilic", "inflammation. being electrophilic these", "being electrophilic these derivatives", "electrophilic these derivatives reversibly", "these derivatives reversibly bind to", "derivatives reversibly bind to nucleophilic", "reversibly bind to nucleophilic residues", "bind to nucleophilic residues on", "to nucleophilic residues on target", "nucleophilic residues on target proteins", "on target proteins thiolates", "target proteins thiolates of", "proteins thiolates of cysteines", "thiolates of cysteines and amino", "of cysteines and amino groups", "cysteines and amino groups of", "and amino groups of histidine", "amino groups of histidine and", "groups of histidine and lysine", "and lysine triggering", "lysine triggering the", "triggering the activation of cytoprotective", "the activation of cytoprotective pathways.", "activation of cytoprotective pathways. these", "of cytoprotective pathways. these include", "cytoprotective pathways. these include the", "pathways. these include the nrf2", "these include the nrf2 antioxidant", "include the nrf2 antioxidant response", "nrf2 antioxidant response the", "antioxidant response the heat", "response the heat shock", "the heat shock response and", "heat shock response and the", "shock response and the peroxisome", "response and the peroxisome proliferator", "and the peroxisome proliferator activated", "the peroxisome proliferator activated receptor", "peroxisome proliferator activated receptor \u03b3", "activated receptor \u03b3 ppar\u03b3", "\u03b3 ppar\u03b3 and", "ppar\u03b3 and suppressing the", "and suppressing the nf \u03bab", "suppressing the nf \u03bab proinflammatory", "the nf \u03bab proinflammatory pathway", "\u03bab proinflammatory pathway cipollina", "proinflammatory pathway cipollina 2015", "pathway cipollina 2015 .", "2015 . thus these", ". thus these electrophilic", "thus these electrophilic derivatives", "these electrophilic derivatives transduce anti", "electrophilic derivatives transduce anti inflammatory", "derivatives transduce anti inflammatory actions", "transduce anti inflammatory actions rather", "anti inflammatory actions rather than", "inflammatory actions rather than suppress", "actions rather than suppress the", "rather than suppress the production", "than suppress the production of", "suppress the production of pro", "the production of pro inflammatory", "production of pro inflammatory arachidonic", "of pro inflammatory arachidonic acid", "pro inflammatory arachidonic acid metabolites.", "inflammatory arachidonic acid metabolites. an", "arachidonic acid metabolites. an oxo", "acid metabolites. an oxo derivative", "metabolites. an oxo derivative of", "an oxo derivative of epa", "oxo derivative of epa has", "derivative of epa has been", "of epa has been shown", "epa has been shown to", "has been shown to ablate", "been shown to ablate leukemia", "shown to ablate leukemia stem", "to ablate leukemia stem cells", "ablate leukemia stem cells in", "leukemia stem cells in mice", "cells in mice which", "in mice which may", "mice which may represent", "which may represent a novel", "may represent a novel chemoprotective", "represent a novel chemoprotective action", "a novel chemoprotective action for", "novel chemoprotective action for some", "chemoprotective action for some oxo", "action for some oxo derivatives", "some oxo derivatives hedge", "oxo derivatives hedge et", "derivatives hedge et al.", "et al. 2011 finch", "al. 2011 finch et", "2011 finch et al.", "finch et al. 2015 .", "et al. 2015 . in", "al. 2015 . in humans", ". in humans dietary", "in humans dietary supplementation", "humans dietary supplementation with", "dietary supplementation with \u03c9 3", "supplementation with \u03c9 3 pufas", "with \u03c9 3 pufas has", "\u03c9 3 pufas has been", "3 pufas has been reported", "pufas has been reported to", "has been reported to increase", "been reported to increase the", "reported to increase the formation", "to increase the formation of", "increase the formation of oxo", "the formation of oxo derivatives", "of oxo derivatives yates", "oxo derivatives yates et", "derivatives yates et al.", "yates et al. 2014 .", "et al. 2014 . the", "al. 2014 . the enzymes", "2014 . the enzymes cyclooxygenases", "the enzymes cyclooxygenases cox", "lipoxygenases los and", "los and cytochromes p450s", "and cytochromes p450s acting", "cytochromes p450s acting alone", "p450s acting alone or", "acting alone or in concerted", "alone or in concerted transcellular", "or in concerted transcellular biosynthesis", "concerted transcellular biosynthesis initially", "transcellular biosynthesis initially form", "biosynthesis initially form epoxy", "initially form epoxy or hydroxy", "form epoxy or hydroxy intermediates", "epoxy or hydroxy intermediates of", "or hydroxy intermediates of \u03c9", "hydroxy intermediates of \u03c9 3", "intermediates of \u03c9 3 pufas", "of \u03c9 3 pufas docosahexaenoic", "\u03c9 3 pufas docosahexaenoic acid", "pufas docosahexaenoic acid dha", "dha docosapentaenoic acid", "docosapentaenoic acid dpan 3", "dpan 3 and eicosapentaenoic", "3 and eicosapentaenoic acid", "and eicosapentaenoic acid epa", "acid epa before", "epa before these are", "before these are further oxidised", "these are further oxidised to", "are further oxidised to electrophilic", "further oxidised to electrophilic \u03b1", "oxidised to electrophilic \u03b1 \u03b2", "to electrophilic \u03b1 \u03b2 unsaturated", "electrophilic \u03b1 \u03b2 unsaturated keto", "\u03b1 \u03b2 unsaturated keto derivatives", "\u03b2 unsaturated keto derivatives by", "unsaturated keto derivatives by cellular", "keto derivatives by cellular dehydrogenases." ] }, { "record_id": "GLY_000594_1_1540", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9028335", "r hsa", "hsa 9028335", "r hsa 9028335" ] }, { "record_id": "GLY_000594_1_1540", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated ntrk2", "ntrk2 signals", "signals through", "through pi3k", "activated ntrk2 signals", "ntrk2 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the cellular", "the cellular sterol", "cellular sterol load", "sterol load by", "load by limiting", "by limiting cholesterol", "limiting cholesterol uptake", "uptake attenuating", "attenuating cholesterol biosynthesis", "cholesterol biosynthesis and", "biosynthesis and promoting", "and promoting cholesterol", "promoting cholesterol efflux.", "cholesterol efflux. this", "efflux. this reactome", "this reactome module", "reactome module describes", "module describes the", "describes the nr1h2", "the nr1h2 &", "& nr1h3 regulated", "nr1h3 regulated expression", "regulated expression of", "expression of mylip", "mylip idol", "idol gene", "gene an", "an e3 ubiquitin", "e3 ubiquitin ligase", "ligase that", "that triggers ubiquitination", "triggers ubiquitination of", "ubiquitination of the", "of the low", "the low density", "low density lipoprotein", "density lipoprotein receptor", "receptor ldlr", "ldlr on", "on its cytoplasmic", "its cytoplasmic domain", "domain targeting", "targeting it for", "it for degradation", "for degradation and", "degradation and thereby", "and thereby limiting", "thereby limiting cholesterol", "uptake zelcer", "zelcer n et", "n et al.", "et al. 2009", "2009 zhang", "zhang l et", "l et al.", "et al. 2012", "al. 2012 .", "liver x receptors nr1h3", "receptors nr1h3 lxr", "nr1h3 lxr alpha", "lxr alpha and", "alpha and nr1h2", "and nr1h2 lxr", "nr1h2 lxr beta", "lxr beta are", "beta are sterol", "are sterol responsive transcription", "sterol responsive transcription factors", "responsive transcription factors that", "transcription factors that become", "factors that become activated", "that become activated upon", "become activated upon the", "activated upon the engagement", "upon the engagement with", "the engagement with their", "engagement with their cognate", "with their cognate oxysterol", "their cognate oxysterol ligands.", "cognate oxysterol ligands. ligand", "oxysterol ligands. ligand activated", "ligands. ligand activated nr1h2", "ligand activated nr1h2 &", "activated nr1h2 & nr1h3", "nr1h2 & nr1h3 induce", "& nr1h3 induce a", "nr1h3 induce a genetic", "induce a genetic program", "a genetic program aimed", "genetic program aimed at", "program aimed at reducing", "aimed at reducing the", "at reducing the cellular", "reducing the cellular sterol", "the cellular sterol load", "cellular sterol load by", "sterol load by limiting", "load by limiting cholesterol", "by limiting cholesterol uptake", "cholesterol uptake attenuating", "uptake attenuating cholesterol", "attenuating cholesterol biosynthesis and", "cholesterol biosynthesis and promoting", "biosynthesis and promoting cholesterol", "and promoting cholesterol efflux.", "promoting cholesterol efflux. this", "cholesterol efflux. this reactome", "efflux. this reactome module", "this reactome module describes", "reactome module describes the", "module describes the nr1h2", "describes the nr1h2 &", "the nr1h2 & nr1h3", "nr1h2 & nr1h3 regulated", "& nr1h3 regulated expression", "nr1h3 regulated expression of", "regulated expression of mylip", "of mylip idol", "gene an e3", "an e3 ubiquitin ligase", "ubiquitin ligase that", "ligase that triggers", "that triggers ubiquitination of", "triggers ubiquitination of the", "ubiquitination of the low", "of the low density", "the low density lipoprotein", "low density lipoprotein receptor", "lipoprotein receptor ldlr", "ldlr on its", "on its cytoplasmic domain", "cytoplasmic domain targeting", "domain targeting it", "targeting it for degradation", "it for degradation and", "for degradation and thereby", "degradation and thereby limiting", "and thereby limiting cholesterol", "thereby limiting cholesterol uptake", "cholesterol uptake zelcer", "uptake zelcer n", "zelcer n et al.", "n et al. 2009", "al. 2009 zhang", "2009 zhang l", "zhang l et al.", "l et al. 2012", "et al. 2012 .", "x receptors nr1h3 lxr", "receptors nr1h3 lxr alpha", "lxr alpha and nr1h2", "and nr1h2 lxr beta", "lxr beta are sterol", "beta are sterol responsive", "are sterol responsive transcription factors", "sterol responsive transcription factors that", "responsive transcription factors that become", "transcription factors that become activated", "factors that become activated upon", "that become activated upon the", "become activated upon the engagement", "activated upon the engagement with", "upon the engagement with their", "the engagement with their cognate", "engagement with their cognate oxysterol", "with their cognate oxysterol ligands.", "their cognate oxysterol ligands. ligand", "cognate oxysterol ligands. ligand activated", "oxysterol ligands. ligand activated nr1h2", "ligands. ligand activated nr1h2 &", "ligand activated nr1h2 & nr1h3", "activated nr1h2 & nr1h3 induce", "nr1h2 & nr1h3 induce a", "& nr1h3 induce a genetic", "nr1h3 induce a genetic program", "induce a genetic program aimed", "a genetic program aimed at", "genetic program aimed at reducing", "program aimed at reducing the", "aimed at reducing the cellular", "at reducing the cellular sterol", "reducing the cellular sterol load", "the cellular sterol load by", "cellular sterol load by limiting", "sterol load by limiting cholesterol", "load by limiting cholesterol uptake", "limiting cholesterol uptake attenuating", "cholesterol uptake attenuating cholesterol", "uptake attenuating cholesterol biosynthesis", "attenuating cholesterol biosynthesis and promoting", "cholesterol biosynthesis and promoting cholesterol", "biosynthesis and promoting cholesterol efflux.", "and promoting cholesterol efflux. this", "promoting cholesterol efflux. this reactome", "cholesterol efflux. this reactome module", "efflux. this reactome module describes", "this reactome module describes the", "reactome module describes the nr1h2", "module describes the nr1h2 &", "describes the nr1h2 & nr1h3", "the nr1h2 & nr1h3 regulated", "nr1h2 & nr1h3 regulated expression", "& nr1h3 regulated expression of", "nr1h3 regulated expression of mylip", "expression of mylip idol", "mylip idol gene", "idol gene an", "gene an e3 ubiquitin", "e3 ubiquitin ligase that", "ubiquitin ligase that triggers", "ligase that triggers ubiquitination", "that triggers ubiquitination of the", "triggers ubiquitination of the low", "ubiquitination of the low density", "of the low density lipoprotein", "the low density lipoprotein receptor", "density lipoprotein receptor ldlr", "receptor ldlr on", "ldlr on its cytoplasmic", "its cytoplasmic domain targeting", "cytoplasmic domain targeting it", "domain targeting it for", "targeting it for degradation and", "it for degradation and thereby", "for degradation and thereby limiting", "degradation and thereby limiting cholesterol", "and thereby limiting cholesterol uptake", "limiting cholesterol uptake zelcer", "cholesterol uptake zelcer n", "uptake zelcer n et", "zelcer n et al. 2009", "et al. 2009 zhang", "al. 2009 zhang l", "2009 zhang l et", "zhang l et al. 2012", "l et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1542", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9032500", "r hsa", "hsa 9032500", "r hsa 9032500" ] }, { "record_id": "GLY_000594_1_1542", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated ntrk2", "ntrk2 signals", "signals through", "through fyn", "activated ntrk2 signals", "ntrk2 signals through", "signals through fyn", "activated ntrk2 signals through", "ntrk2 signals through fyn", "activated ntrk2 signals through fyn", "in mouse", "mouse brain", "fyn activation", "activation downstream", "downstream of", "of bdnf", "bdnf induced", "induced ntrk2", "signaling results", "results in", "in increased", "increased protein", "protein levels", "levels of", "of ampa", "ampa receptor", "receptor subunits", "subunits gria2", "and gria1", "without change", "change in", "in mrna", "mrna levels", "narisawa saito", "saito et", "et al.", "al. 1999", "1999 .

              bdnf", ".

              bdnf mediated", "mediated activation", "activation of", "of ntrk2", "ntrk2 increases", "increases phosphorylation", "phosphorylation of", "of voltage", "voltage gated", "gated sodium", "sodium channels", "channels by", "by fyn", "resulting in", "in decrease", "decrease of", "of sodium", "sodium currents", "ahn et", "al. 2007", "2007 .

              fyn", ".

              fyn activation", "ntrk2 is", "is implicated", "implicated in", "in olygodendrocyte", "olygodendrocyte myelination", "myelination and", "and contributes", "contributes to", "to bdnf", "induced activation", "of erk1/2", "through an", "an unknown", "unknown mechanism", "peckham et", "al. 2015", "2015 .

              besides", ".

              besides acting", "acting downstream", "fyn and", "and other", "other src", "src kinases", "activated by", "by other", "other receptors", "receptors such", "such as", "as gpcrs", "may phosphorylate", "phosphorylate ntrk2", "ntrk2 and", "and enhance", "enhance its", "its catalytic", "catalytic activity", "rajagopal and", "and chao", "chao 2006", "huang and", "and mcnamara", "mcnamara 2010", "2010 .", "in mouse brain", "brain fyn", "fyn activation downstream", "activation downstream of", "downstream of bdnf", "of bdnf induced", "bdnf induced ntrk2", "ntrk2 trkb", "trkb signaling", "signaling results in", "results in increased", "in increased protein", "increased protein levels", "protein levels of", "levels of ampa", "of ampa receptor", "ampa receptor subunits", "receptor subunits gria2", "gria2 glur2", "gria3 glur3", "glur3 and", "gria1 glur1", "glur1 without", "without change in", "change in mrna", "in mrna levels", "levels narisawa", "narisawa saito et", "saito et al.", "et al. 1999", "al. 1999 .

              bdnf", "1999 .

              bdnf mediated", ".

              bdnf mediated activation", "mediated activation of", "activation of ntrk2", "of ntrk2 increases", "ntrk2 increases phosphorylation", "increases phosphorylation of", "phosphorylation of voltage", "of voltage gated", "voltage gated sodium", "gated sodium channels", "sodium channels by", "channels by fyn", "fyn resulting", "resulting in decrease", "in decrease of", "decrease of sodium", "of sodium currents", "currents ahn", "ahn et al.", "et al. 2007", "al. 2007 .

              fyn", "2007 .

              fyn activation", ".

              fyn activation downstream", "downstream of ntrk2", "of ntrk2 is", "ntrk2 is implicated", "is implicated in", "implicated in olygodendrocyte", "in olygodendrocyte myelination", "olygodendrocyte myelination and", "myelination and contributes", "and contributes to", "contributes to bdnf", "to bdnf induced", "bdnf induced activation", "induced activation of", "activation of erk1/2", "erk1/2 mapk3/1", "mapk3/1 through", "through an unknown", "an unknown mechanism", "mechanism peckham", "peckham et al.", "et al. 2015", "al. 2015 .

              besides", "2015 .

              besides acting", ".

              besides acting downstream", "acting downstream of", "ntrk2 fyn", "fyn and other", "and other src", "other src kinases", "kinases activated", "activated by other", "by other receptors", "other receptors such", "receptors such as", "such as gpcrs", "gpcrs may", "may phosphorylate ntrk2", "phosphorylate ntrk2 and", "ntrk2 and enhance", "and enhance its", "enhance its catalytic", "its catalytic activity", "activity rajagopal", "rajagopal and chao", "and chao 2006", "2006 huang", "huang and mcnamara", "and mcnamara 2010", "mcnamara 2010 .", "mouse brain fyn", "brain fyn activation", "fyn activation downstream of", "activation downstream of bdnf", "downstream of bdnf induced", "of bdnf induced ntrk2", "induced ntrk2 trkb", "trkb signaling results", "signaling results in increased", "results in increased protein", "in increased protein levels", "increased protein levels of", "protein levels of ampa", "levels of ampa receptor", "of ampa receptor subunits", "ampa receptor subunits gria2", "subunits gria2 glur2", "glur2 gria3", "glur3 and gria1", "and gria1 glur1", "glur1 without change", "without change in mrna", "change in mrna levels", "mrna levels narisawa", "levels narisawa saito", "narisawa saito et al.", "saito et al. 1999", "et al. 1999 .

              bdnf", "al. 1999 .

              bdnf mediated", "1999 .

              bdnf mediated activation", ".

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              fyn", "al. 2007 .

              fyn activation", "2007 .

              fyn activation downstream", ".

              fyn activation downstream of", "activation downstream of ntrk2", "downstream of ntrk2 is", "of ntrk2 is implicated", "ntrk2 is implicated in", "is implicated in olygodendrocyte", "implicated in olygodendrocyte myelination", "in olygodendrocyte myelination and", "olygodendrocyte myelination and contributes", "myelination and contributes to", "and contributes to bdnf", "contributes to bdnf induced", "to bdnf induced activation", "bdnf induced activation of", "induced activation of erk1/2", "of erk1/2 mapk3/1", "mapk3/1 through an", "through an unknown mechanism", "unknown mechanism peckham", "mechanism peckham et", "peckham et al. 2015", "et al. 2015 .

              besides", "al. 2015 .

              besides acting", "2015 .

              besides acting downstream", ".

              besides acting downstream of", "acting downstream of ntrk2", "of ntrk2 fyn", "ntrk2 fyn and", "fyn and other src", "and other src kinases", "src kinases activated", "kinases activated by", "activated by other receptors", "by other receptors such", "other receptors such as", "receptors such as gpcrs", "as gpcrs may", "gpcrs may phosphorylate", "may phosphorylate ntrk2 and", "phosphorylate ntrk2 and enhance", "ntrk2 and enhance its", "and enhance its catalytic", "enhance its catalytic activity", "catalytic activity rajagopal", "activity rajagopal and", "rajagopal and chao 2006", "chao 2006 huang", "2006 huang and", "huang and mcnamara 2010", "and mcnamara 2010 .", "in mouse brain fyn", "mouse brain fyn activation", "brain fyn activation downstream", "fyn activation downstream of bdnf", "activation downstream of bdnf induced", "downstream of bdnf induced ntrk2", "bdnf induced ntrk2 trkb", "ntrk2 trkb signaling", "trkb signaling results in", "signaling results in increased protein", "results in increased protein levels", "in increased protein levels of", "increased protein levels of ampa", "protein levels of ampa receptor", "levels of ampa receptor subunits", "of ampa receptor subunits gria2", "receptor subunits gria2 glur2", "gria3 glur3 and", "gria1 glur1 without", "glur1 without change in", "without change in mrna levels", "in mrna levels narisawa", "mrna levels narisawa saito", "levels narisawa saito et", "narisawa saito et al. 1999", "saito et al. 1999 .

              bdnf", "et al. 1999 .

              bdnf mediated", "al. 1999 .

              bdnf mediated activation", "1999 .

              bdnf mediated activation of", ".

              bdnf mediated activation of ntrk2", "mediated activation of ntrk2 increases", "activation of ntrk2 increases phosphorylation", "of ntrk2 increases phosphorylation of", "ntrk2 increases phosphorylation of voltage", "increases phosphorylation of voltage gated", "phosphorylation of voltage gated sodium", "of voltage gated sodium channels", "voltage gated sodium channels by", "gated sodium channels by fyn", "channels by fyn resulting", "by fyn resulting in", "fyn resulting in decrease", "resulting in decrease of sodium", "in decrease of sodium currents", "of sodium currents ahn", "sodium currents ahn et", "currents ahn et al.", "ahn et al. 2007 .

              fyn", "et al. 2007 .

              fyn activation", "al. 2007 .

              fyn activation downstream", "2007 .

              fyn activation downstream of", ".

              fyn activation downstream of ntrk2", "activation downstream of ntrk2 is", "downstream of ntrk2 is implicated", "of ntrk2 is implicated in", "ntrk2 is implicated in olygodendrocyte", "is implicated in olygodendrocyte myelination", "implicated in olygodendrocyte myelination and", "in olygodendrocyte myelination and contributes", "olygodendrocyte myelination and contributes to", "myelination and contributes to bdnf", "and contributes to bdnf induced", "contributes to bdnf induced activation", "to bdnf induced activation of", "bdnf induced activation of erk1/2", "activation of erk1/2 mapk3/1", "erk1/2 mapk3/1 through", "mapk3/1 through an unknown", "an unknown mechanism peckham", "unknown mechanism peckham et", "mechanism peckham et al.", "peckham et al. 2015 .

              besides", "et al. 2015 .

              besides acting", "al. 2015 .

              besides acting downstream", "2015 .

              besides acting downstream of", ".

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rac1 by binding to", "rac1 by binding to ntrk", "by binding to ntrk associated", "binding to ntrk associated fyn", "ntrk associated fyn namekata", "associated fyn namekata et", "fyn namekata et al.", "namekata et al. 2010 .", "et al. 2010 . alternatively", "2010 . alternatively dock3", ". alternatively dock3 can", "dock3 can upon poorly", "can upon poorly elucidated", "upon poorly elucidated rhog activation", "poorly elucidated rhog activation by", "elucidated rhog activation by the", "rhog activation by the bdnf:ntrk2", "activation by the bdnf:ntrk2 complex", "the bdnf:ntrk2 complex bind", "bdnf:ntrk2 complex bind to", "complex bind to the", "bind to the rhog:gtp complex", "to the rhog:gtp complex and", "the rhog:gtp complex and activate", "rhog:gtp complex and activate rac1", "complex and activate rac1 in", "and activate rac1 in an", "activate rac1 in an elmo1", "rac1 in an elmo1 dependent", "in an elmo1 dependent manner", "elmo1 dependent manner namekata", "dependent manner namekata et", "manner namekata et al.", "namekata et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1544", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9032845", "r hsa", "hsa 9032845", "r hsa 9032845" ] }, { "record_id": "GLY_000594_1_1544", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated ntrk2", "ntrk2 signals", "signals through", "through cdk5", "activated ntrk2 signals", "ntrk2 signals through", "signals through cdk5", "activated ntrk2 signals through", "ntrk2 signals through cdk5", "activated ntrk2 signals through cdk5", "in complex", "complex with", "with its", "its activator", "activator cdk5r1", "binds to", "to bdnf", "bdnf activated", "trkb .", ". ntrk2", "ntrk2 promotes", "promotes cdk5", "cdk5 catalytic", "catalytic activity", "activity by", "by phosphorylating", "phosphorylating cdk5", "cdk5 at", "at tyrosine", "tyrosine residue", "residue y15", "cheung et", "et al.", "al. 2007", "although cdk5", "cdk5 can", "can also", "also be", "be phosphorylated", "phosphorylated at", "at y15", "y15 independently", "independently of", "of ntrk2", "zhao et", "al. 2009", "2009 .", ". cdk5", "cdk5 phosphorylates", "phosphorylates serine", "serine residue", "residue s479", "s479 of", "corresponds to", "to s478", "s478 in", "in mouse", "mouse and", "and rat", ". phosphorylation", "phosphorylation of", "ntrk2 at", "at s479", "s479 is", "is needed", "needed for", "for bdnf", "bdnf triggered", "triggered dendritic", "dendritic growth", "hippocampal long", "long term", "term potentiation", "and spatial", "spatial memory", "lai et", "al. 2012", "2012 .", ". these", "these processes", "processes involve", "involve ntrk2", "ntrk2 mediated", "mediated activation", "activation of", "of rho", "rho gtpases", "gtpases rac1", "and possibly", "possibly cdc42", "2007 .", ". in", "in cultured", "cultured isolated", "isolated neurons", "phosphorylation at", "s479 affects", "affects 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              cdk5", ".

              cdk5 mediated", "mediated phosphorylation", "ntrk2 was", "was suggested", "suggested to", "to influence", "influence the", "the level", "level of", "of akt", "akt activity", "downstream mtor", "mtor signaling", "signaling and", "and dlg4", "psd 95", "but further", "further elucidation", "elucidation is", "2012 .

              signaling", ".

              signaling by", "by trkb", "trkb and", "and cdk5", "cdk5 plays", "plays a", "a role", "role in", "in inflammation", "inflammation induced", "induced hypersensitivity", "hypersensitivity to", "to heat", "heat triggered", "triggered pain", "pain in", "in rats", "zhang et", "al. 2014", "2014 .", "cdk5 in", "in complex with", "complex with its", "with its activator", "its activator cdk5r1", "cdk5r1 p35", "binds to bdnf", "to bdnf activated", "bdnf activated ntrk2", "ntrk2 trkb", "trkb . ntrk2", ". ntrk2 promotes", "ntrk2 promotes cdk5", "promotes cdk5 catalytic", "cdk5 catalytic activity", "catalytic activity by", "activity by phosphorylating", "by phosphorylating cdk5", "phosphorylating cdk5 at", "cdk5 at tyrosine", "at tyrosine residue", "tyrosine residue y15", "y15 cheung", "cheung et al.", "et al. 2007", "although cdk5 can", "cdk5 can also", "can also be", "also be phosphorylated", "be phosphorylated at", "phosphorylated at y15", "at y15 independently", "y15 independently of", "independently of ntrk2", "ntrk2 zhao", "zhao et al.", "et al. 2009", "al. 2009 .", "2009 . cdk5", ". cdk5 phosphorylates", "cdk5 phosphorylates serine", "phosphorylates serine residue", "serine residue s479", "residue s479 of", "s479 of ntrk2", "ntrk2 corresponds", "corresponds to s478", "to s478 in", "s478 in mouse", "in mouse and", "mouse and rat", "2007 zhao", "2009 . phosphorylation", ". phosphorylation of", "phosphorylation of ntrk2", "of ntrk2 at", "ntrk2 at s479", "at s479 is", "s479 is needed", "is needed for", "needed for bdnf", "for bdnf triggered", "bdnf triggered dendritic", "triggered dendritic growth", "growth cheung", "hippocampal long term", "long term potentiation", "potentiation ltp", "ltp and", "and spatial memory", "memory lai", "lai et al.", "et al. 2012", "al. 2012 .", "2012 . these", ". these processes", "these processes involve", "processes involve ntrk2", "involve ntrk2 mediated", "ntrk2 mediated activation", "mediated activation of", "activation of rho", "of rho gtpases", "rho gtpases rac1", "rac1 lai", "2012 and", "and possibly cdc42", "cdc42 cheung", "al. 2007 .", "2007 . in", ". in cultured", "in cultured isolated", "cultured isolated neurons", "neurons phosphorylation", "phosphorylation at s479", "at s479 affects", "s479 affects localization", "affects localization of", "localization of ntrk2", "but this does", "this does not", "does not appear", "not appear to", "appear to be", "to be the", "be the case", "the case in", "case in vivo", "vivo lai", "al. 2012 .

              cdk5", "2012 .

              cdk5 mediated", ".

              cdk5 mediated phosphorylation", "mediated phosphorylation of", "of ntrk2 was", "ntrk2 was suggested", "was suggested to", "suggested to influence", "to influence the", "influence the level", "the level of", "level of akt", "of akt activity", "activity downstream", "downstream mtor signaling", "mtor signaling and", "signaling and dlg4", "dlg4 psd", "95 expression", "expression but", "but further elucidation", "further elucidation is", "elucidation is needed", "needed lai", "al. 2012 .

              signaling", "2012 .

              signaling by", ".

              signaling by trkb", "by trkb and", "trkb and cdk5", "and cdk5 plays", "cdk5 plays a", "plays a role", "a role in", "role in inflammation", "in inflammation induced", "inflammation induced hypersensitivity", "induced hypersensitivity to", "hypersensitivity to heat", "to heat triggered", "heat triggered pain", "triggered pain in", "pain in rats", "rats zhang", "zhang et al.", "et al. 2014", "al. 2014 .", "cdk5 in complex", "in complex with its", "complex with its activator", "with its activator cdk5r1", "activator cdk5r1 p35", "p35 binds", "binds to bdnf activated", "to bdnf activated ntrk2", "activated ntrk2 trkb", "ntrk2 trkb .", "trkb . ntrk2 promotes", ". ntrk2 promotes cdk5", "ntrk2 promotes cdk5 catalytic", "promotes cdk5 catalytic activity", "cdk5 catalytic activity by", "catalytic activity by phosphorylating", "activity by phosphorylating cdk5", "by phosphorylating cdk5 at", "phosphorylating cdk5 at tyrosine", "cdk5 at tyrosine residue", "at tyrosine residue y15", "residue y15 cheung", "y15 cheung et", "cheung et al. 2007", "2007 although", "although cdk5 can also", "cdk5 can also be", "can also be phosphorylated", "also be phosphorylated at", "be phosphorylated at y15", "phosphorylated at y15 independently", "at y15 independently of", "y15 independently of ntrk2", "of ntrk2 zhao", "ntrk2 zhao et", "zhao et al. 2009", "et al. 2009 .", "al. 2009 . cdk5", "2009 . cdk5 phosphorylates", ". cdk5 phosphorylates serine", "cdk5 phosphorylates serine residue", "phosphorylates serine residue s479", "serine residue s479 of", "residue s479 of ntrk2", "of ntrk2 corresponds", "ntrk2 corresponds to", "corresponds to s478 in", "to s478 in mouse", "s478 in mouse and", "in mouse and rat", "rat cheung", "al. 2007 zhao", "2007 zhao et", "al. 2009 . phosphorylation", "2009 . phosphorylation of", ". phosphorylation of ntrk2", "phosphorylation of ntrk2 at", "of ntrk2 at s479", "ntrk2 at s479 is", "at s479 is needed", "s479 is needed for", "is needed for bdnf", "needed for bdnf triggered", "for bdnf triggered dendritic", "bdnf triggered dendritic growth", "dendritic growth cheung", "growth cheung et", "2007 hippocampal", "hippocampal long term potentiation", "term potentiation ltp", "ltp and spatial", "spatial memory lai", "memory lai et", "lai et al. 2012", "et al. 2012 .", "al. 2012 . these", "2012 . these processes", ". these processes involve", "these processes involve ntrk2", "processes involve ntrk2 mediated", "involve ntrk2 mediated activation", "ntrk2 mediated activation of", "mediated activation of rho", "activation of rho gtpases", "of rho gtpases rac1", "gtpases rac1 lai", "rac1 lai et", "al. 2012 and", "2012 and possibly", "possibly cdc42 cheung", "cdc42 cheung et", "et al. 2007 .", "al. 2007 . in", "2007 . in cultured", ". in cultured isolated", "in cultured isolated neurons", "isolated neurons phosphorylation", "neurons phosphorylation at", "phosphorylation at s479 affects", "at s479 affects localization", "s479 affects localization of", "affects localization of ntrk2", "2009 but", "but this does not", "this does not appear", "does not appear to", "not appear to be", "appear to be the", "to be the case", "be the case in", "the case in vivo", "in vivo lai", "vivo lai et", "et al. 2012 .

              cdk5", "al. 2012 .

              cdk5 mediated", "2012 .

              cdk5 mediated phosphorylation", ".

              cdk5 mediated phosphorylation of", "mediated phosphorylation of ntrk2", "phosphorylation of ntrk2 was", "of ntrk2 was suggested", "ntrk2 was suggested to", "was suggested to influence", "suggested to influence the", "to influence the level", "influence the level of", "the level of akt", "level of akt activity", "akt activity downstream", "activity downstream mtor", "downstream mtor signaling and", "mtor signaling and dlg4", "and dlg4 psd", "dlg4 psd 95", "psd 95 expression", "expression but further", "but further elucidation is", "further elucidation is needed", "is needed lai", "needed lai et", "et al. 2012 .

              signaling", "al. 2012 .

              signaling by", "2012 .

              signaling by trkb", ".

              signaling by trkb and", "by trkb and cdk5", "trkb and cdk5 plays", "and cdk5 plays a", "cdk5 plays a role", "plays a role in", "a role in inflammation", "role in inflammation induced", "in inflammation induced hypersensitivity", "inflammation induced hypersensitivity to", "induced hypersensitivity to heat", "hypersensitivity to heat triggered", "to heat triggered pain", "heat triggered pain in", "triggered pain in rats", "in rats zhang", "rats zhang et", "zhang et al. 2014", "et al. 2014 .", "cdk5 in complex with", "in complex with its activator", "complex with its activator cdk5r1", "its activator cdk5r1 p35", "p35 binds to", "binds to bdnf activated ntrk2", "bdnf activated ntrk2 trkb", "activated ntrk2 trkb .", "ntrk2 trkb . ntrk2", "trkb . ntrk2 promotes cdk5", ". ntrk2 promotes cdk5 catalytic", "ntrk2 promotes cdk5 catalytic activity", "promotes cdk5 catalytic activity by", "cdk5 catalytic activity by phosphorylating", "catalytic activity by phosphorylating cdk5", "activity by phosphorylating cdk5 at", "by phosphorylating cdk5 at tyrosine", "phosphorylating cdk5 at tyrosine residue", "cdk5 at tyrosine residue y15", "tyrosine residue y15 cheung", "residue y15 cheung et", "y15 cheung et al.", "al. 2007 although", "2007 although cdk5", "although cdk5 can also be", "cdk5 can also be phosphorylated", "can also be phosphorylated at", "also be phosphorylated at y15", "be phosphorylated at y15 independently", "phosphorylated at y15 independently of", "at y15 independently of ntrk2", "independently of ntrk2 zhao", "of ntrk2 zhao et", "ntrk2 zhao et al.", "zhao et al. 2009 .", "et al. 2009 . cdk5", "al. 2009 . cdk5 phosphorylates", "2009 . cdk5 phosphorylates serine", ". cdk5 phosphorylates serine residue", "cdk5 phosphorylates serine residue s479", "phosphorylates serine residue s479 of", "serine residue s479 of ntrk2", "s479 of ntrk2 corresponds", "of ntrk2 corresponds to", "ntrk2 corresponds to s478", "corresponds to s478 in mouse", "to s478 in mouse and", "s478 in mouse and rat", "and rat cheung", "rat cheung et", "et al. 2007 zhao", "al. 2007 zhao et", "2007 zhao et al.", "et al. 2009 . phosphorylation", "al. 2009 . phosphorylation of", "2009 . phosphorylation of ntrk2", ". phosphorylation of ntrk2 at", "phosphorylation of ntrk2 at s479", "of ntrk2 at s479 is", "ntrk2 at s479 is needed", "at s479 is needed for", "s479 is needed for bdnf", "is needed for bdnf triggered", "needed for bdnf triggered dendritic", "for bdnf triggered dendritic growth", "triggered dendritic growth cheung", "dendritic growth cheung et", "growth cheung et al.", "al. 2007 hippocampal", "2007 hippocampal long", "long term potentiation ltp", "potentiation ltp and", "ltp and spatial memory", "and spatial memory lai", "spatial memory lai et", "memory lai et al.", "lai et al. 2012 .", "et al. 2012 . these", "al. 2012 . these processes", "2012 . these processes involve", ". these processes involve ntrk2", "these processes involve ntrk2 mediated", "processes involve ntrk2 mediated activation", "involve ntrk2 mediated activation of", "ntrk2 mediated activation of rho", "mediated activation of rho gtpases", "activation of rho gtpases rac1", "rho gtpases rac1 lai", "gtpases rac1 lai et", "rac1 lai et al.", "et al. 2012 and", "al. 2012 and possibly", "2012 and possibly cdc42", "and possibly cdc42 cheung", "possibly cdc42 cheung et", "cdc42 cheung et al.", "cheung et al. 2007 .", "et al. 2007 . in", "al. 2007 . in cultured", "2007 . in cultured isolated", ". in cultured isolated neurons", "cultured isolated neurons phosphorylation", "isolated neurons phosphorylation at", "neurons phosphorylation at s479", "phosphorylation at s479 affects localization", "at s479 affects localization of", "s479 affects localization of ntrk2", "localization of ntrk2 zhao", "al. 2009 but", "2009 but this", "but this does not appear", "this does not appear to", "does not appear to be", "not appear to be the", "appear to be the case", "to be the case in", "be the case in vivo", "case in vivo lai", "in vivo lai et", "vivo lai et al.", "lai et al. 2012 .

              cdk5", "et al. 2012 .

              cdk5 mediated", "al. 2012 .

              cdk5 mediated phosphorylation", "2012 .

              cdk5 mediated phosphorylation of", ".

              cdk5 mediated phosphorylation of ntrk2", "mediated phosphorylation of ntrk2 was", "phosphorylation of ntrk2 was suggested", "of ntrk2 was suggested to", "ntrk2 was suggested to influence", "was suggested to influence the", "suggested to influence the level", "to influence the level of", "influence the level of akt", "the level of akt activity", "of akt activity downstream", "akt activity downstream mtor", "activity downstream mtor signaling", "downstream mtor signaling and dlg4", "signaling and dlg4 psd", "and dlg4 psd 95", "95 expression but", "expression but further elucidation", "but further elucidation is needed", "elucidation is needed lai", "is needed lai et", "needed lai et al.", "lai et al. 2012 .

              signaling", "et al. 2012 .

              signaling by", "al. 2012 .

              signaling by trkb", "2012 .

              signaling by trkb and", ".

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              the", "plasma.

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              the", "their plasma.

              the primary", "plasma.

              the primary structure", "primary structure of", "structure of these", "of these antigens", "these antigens is", "antigens is an", "is an oligosaccharide", "an oligosaccharide precursor", "oligosaccharide precursor sequence", "precursor sequence on", "sequence on to", "on to which", "to which one", "which one or", "one or more", "or more sugars", "more sugars are", "sugars are attached", "are attached at", "attached at specific", "at specific locations.", "specific locations. the", "locations. the blood", "the blood group", "blood group oligosaccharide", "group oligosaccharide antigens", "oligosaccharide antigens a", "b and h", "and h are", "h are produced", "are produced by", "produced by enzymes", "by enzymes expressed", "enzymes expressed by", "expressed by these", "by these genes", "these genes and", "genes and form", "and form the", "form the basis", "the basis of", "basis of the", "of the abo", "the abo 'blood", "abo 'blood type'", "'blood type' phenotypes.", "type' phenotypes. a", "phenotypes. a and", "a and b", "and b antigens", "b antigens were", "antigens were originally", "were originally identified", "originally identified on", "identified on red", "on red blood", "red blood cells", "cells rbcs", "rbcs but", "but later identified", "later identified on", "identified on other", "on other cell", "other cell types", "cell types and", "types and in", "and in bodily", "in bodily secretions.", "bodily secretions. the", "secretions. the abo", "blood group system", "group system is", "system is important", "is important in", "important in blood", "in blood transfusion", "transfusion cell/tissue/organ", "cell/tissue/organ transplantation and", "transplantation and forensic", "and forensic evidence", "forensic evidence at", "evidence at crime", "at crime scenes.

              the", "crime scenes.

              the h", "scenes.

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              the", "in secretors.

              the h", "secretors.

              the h antigen", "antigen is abundant", "is abundant in", "abundant in individuals", "in individuals with", "individuals with blood", "with blood group", "blood group o", "group o and", "o and is", "and is the", "is the essential", "the essential precursor", "essential precursor for", "precursor for the", "for the production", "the production of", "production of a", "of a and", "and b antigens.", "b antigens. a", "antigens. a and", "b antigens are", "antigens are formed", "are formed by", "formed by the", "by the action", "the action of", "action of glycosyltransferases", "of glycosyltransferases encoded", "glycosyltransferases encoded by", "encoded by functional", "by functional alleles", "functional alleles at", "alleles at the", "at the abo", "the abo genetic", "abo genetic locus.", "genetic locus. the", "locus. the co", "the co dominant", "co dominant a", "dominant a allele", "a allele encodes", "allele encodes a", "encodes a transferase", "transferase which", "which transfers an", "transfers an n", "an n acetylgalactosamine", "acetylgalactosamine galnac", "galnac sugar", "sugar to the", "to the h", "h antigen forming", "antigen forming the", "forming the a", "the a antigen.", "a antigen. similarly", "similarly the", "co dominant b", "dominant b allele", "b allele encodes", "allele encodes b", "encodes b transferase", "which transfers a", "transfers a galactose", "galactose gal", "gal sugar", "forming the b", "the b antigen.", "b antigen. individuals", "antigen. individuals who", "individuals who have", "who have both", "have both a", "both a and", "and b alleles", "b alleles form", "alleles form the", "form the ab", "the ab antigen.", "ab antigen. individuals", "individuals who are", "who are homozygous", "are homozygous for", "homozygous for the", "for the recessive", "the recessive o", "recessive o allele", "o allele express", "allele express the", "express the h", "h antigen but", "antigen but do", "but do not", "do not form", "not form a", "form a or", "a or b", "or b antigens", "b antigens as", "antigens as they", "as they lack", "they lack both", "lack both the", "both the glycosyltransferase", "the glycosyltransferase enzymes", "glycosyltransferase enzymes for", "enzymes for their", "for their formation.", "their formation. mutant", "formation. mutant alleles", "mutant alleles of", "alleles of the", "of the corresponding", "the corresponding fut1", "corresponding fut1 or", "fut1 or fut2", "or fut2 genes", "fut2 genes result", "genes result in", "result in either", "in either a", "either a h\u2013", "a h\u2013 phenotype", "phenotype bombay", "phenotype oh", "oh or", "or a weak", "a weak h", "weak h phenotype", "phenotype para", "bombay where", "where the affected", "the affected individual", "affected individual cannot", "individual cannot form", "cannot form h", "h a", "antigens kaneko", "kaneko et al.", "et al. 1997", "1997 koda", "koda et al.", "al. 1997 .", "1997 . the", ". the biosyntheses", "the biosyntheses of", "biosyntheses of the", "of the a", "and h antigens", "h antigens are", "antigens are described", "are described in", "described in this", "in this section", "section ewald", "ewald & sumner", "& sumner 2016", "2016 scharberg", "scharberg et al.", "et al. 2016", "al. 2016 .
              ", "perhaps the most important", "the most important and", "most important and widely", "important and widely studied", "and widely studied blood", "widely studied blood group", "studied blood group is", "blood group is the", "group is the abo", "is the abo blood", "the abo blood group.", "abo blood group. it", "blood group. it consists", "group. it consists of", "it consists of antigens", "consists of antigens found", "of antigens found on", "antigens found on the", "found on the outer", "on the outer surface", "the outer surface of", "outer surface of red", "surface of red cells", "of red cells and", "red cells and corresponding", "cells and corresponding antibodies", "and corresponding antibodies in", "corresponding antibodies in plasma.", "antibodies in plasma. the", "in plasma. the majority", "plasma. the majority of", "the majority of the", "majority of the world's", "of the world's population", "world's population ~80%", "~80% are 'secretors'", "are 'secretors' which means", "'secretors' which means that", "which means that the", "means that the antigens", "that the antigens present", "the antigens present in", "antigens present in their", "present in their blood", "in their blood will", "their blood will also", "blood will also be", "will also be found", "also be found in", "be found in other", "found in other body", "in other body fluids", "other body fluids such", "body fluids such as", "fluids such as saliva.", "such as saliva. an", "as saliva. an individual", "saliva. an individual can", "an individual can be", "individual can be a", "can be a secretor", "a secretor se", "se or a", "or a non secretor", "non secretor se", "se and this", "and this is completely", "this is completely independent", "is completely independent of", "completely independent of whether", "independent of whether the", "of whether the individual", "whether the individual is", "the individual is of", "individual is of blood", "is of blood type", "of blood type a", "type a b", "ab or o.", "or o. from a", "o. from a very", "from a very early", "a very early age", "early age the", "age the immune", "the immune system develops", "immune system develops antibodies", "system develops antibodies against", "develops antibodies against whichever", "antibodies against whichever abo", "against whichever abo blood", "whichever abo blood group", "abo blood group antigens", "blood group antigens are", "group antigens are not", "antigens are not found", "are not found on", "not found on the", "found on the individual's", "on the individual's rbcs.", "the individual's rbcs. thus", "rbcs. thus a", "thus a blood", "a blood group a", "blood group a individual", "group a individual will", "a individual will have", "individual will have anti", "will have anti b", "have anti b antibodies", "anti b antibodies and", "b antibodies and a", "antibodies and a blood", "and a blood group", "a blood group b", "blood group b individual", "group b individual will", "b individual will have", "will have anti a", "have anti a antibodies.", "anti a antibodies. individuals", "a antibodies. individuals with", "antibodies. individuals with the", "individuals with the most", "with the most common", "the most common blood", "most common blood group", "o will", "will have both anti", "have both anti a", "both anti a and", "anti a and anti", "a and anti b", "and anti b in", "anti b in their", "b in their plasma.", "in their plasma. blood", "their plasma. blood group", "plasma. blood group ab", "blood group ab is", "group ab is the", "ab is the least", "is the least common", "least common and", "common and these", "and these individuals will", "these individuals will have", "individuals will have neither", "will have neither anti", "have neither anti a", "neither anti a nor", "anti a nor anti", "a nor anti b", "nor anti b in", "b in their plasma.

              the", "in their plasma.

              the primary", "their plasma.

              the primary structure", "plasma.

              the primary structure of", "primary structure of these", "structure of these antigens", "of these antigens is", "these antigens is an", "antigens is an oligosaccharide", "is an oligosaccharide precursor", "an oligosaccharide precursor sequence", "oligosaccharide precursor sequence on", "precursor sequence on to", "sequence on to which", "on to which one", "to which one or", "which one or more", "one or more sugars", "or more sugars are", "more sugars are attached", "sugars are attached at", "are attached at specific", "attached at specific locations.", "at specific locations. the", "specific locations. the blood", "locations. the blood group", "the blood group oligosaccharide", "blood group oligosaccharide antigens", "group oligosaccharide antigens a", "antigens a b", "a b and", "b and h are", "and h are produced", "h are produced by", "are produced by enzymes", "produced by enzymes expressed", "by enzymes expressed by", "enzymes expressed by these", "expressed by these genes", "by these genes and", "these genes and form", "genes and form the", "and form the basis", "form the basis of", "the basis of the", "basis of the abo", "of the abo 'blood", "the abo 'blood type'", "abo 'blood type' phenotypes.", "'blood type' phenotypes. a", "type' phenotypes. a and", "phenotypes. a and b", "a and b antigens", "and b antigens were", "b antigens were originally", "antigens were originally identified", "were originally identified on", "originally identified on red", "identified on red blood", "on red blood cells", "blood cells rbcs", "rbcs but later", "but later identified on", "later identified on other", "identified on other cell", "on other cell types", "other cell types and", "cell types and in", "types and in bodily", "and in bodily secretions.", "in bodily secretions. the", "bodily secretions. the abo", "secretions. the abo blood", "the abo blood group", "abo blood group system", "blood group system is", "group system is important", "system is important in", "is important in blood", "important in blood transfusion", "blood transfusion cell/tissue/organ", "transfusion cell/tissue/organ transplantation", "cell/tissue/organ transplantation and forensic", "transplantation and forensic evidence", "and forensic evidence at", "forensic evidence at crime", "evidence at crime scenes.

              the", "at crime scenes.

              the h", "crime scenes.

              the h antigen", "scenes.

              the h antigen is", "h antigen is formed", "antigen is formed with", "is formed with the", "formed with the addition", "with the addition of", "the addition of a", "addition of a fucose", "of a fucose sugar", "a fucose sugar onto", "fucose sugar onto one", "sugar onto one of", "onto one of two", "one of two precursor", "of two precursor oligosaccharide", "two precursor oligosaccharide sequences", "oligosaccharide sequences type", "sequences type 1", "type 1 chains are", "1 chains are gal", "chains are gal \u03b21", "are gal \u03b21 3", "gal \u03b21 3 glcnac", "\u03b21 3 glcnac \u03b21", "3 glcnac \u03b21 3", "glcnac \u03b21 3 gal", "\u03b21 3 gal r", "3 gal r and", "gal r and type", "r and type 2", "and type 2 chains", "type 2 chains are", "2 chains are gal", "are gal \u03b21 4", "gal \u03b21 4 glcnac", "\u03b21 4 glcnac \u03b21", "4 glcnac \u03b21 3", "gal r where", "r where r", "where r is a", "r is a glycoprotein", "a glycoprotein type", "glycoprotein type 1", "type 1 or", "1 or glycosphingolipid", "or glycosphingolipid type", "glycosphingolipid type 2", "type 2 . type", "2 . type 2", ". type 2 chains", "2 chains are only", "chains are only found", "are only found on", "only found on rbcs", "on rbcs epithelial", "rbcs epithelial cells", "epithelial cells and endothelial", "cells and endothelial cells.", "and endothelial cells. the", "endothelial cells. the h", "cells. the h gene", "the h gene expressed", "h gene expressed in", "gene expressed in hematopoietic", "expressed in hematopoietic cells", "in hematopoietic cells produces", "hematopoietic cells produces \u03b1", "cells produces \u03b1 1", "produces \u03b1 1 2", "\u03b1 1 2 fucosyltransferase", "1 2 fucosyltransferase 1", "fucosyltransferase 1 fut1", "fut1 which adds", "which adds a fucose", "adds a fucose to", "a fucose to type", "fucose to type 2", "to type 2 chains", "type 2 chains to", "2 chains to form", "chains to form the", "to form the h", "form the h antigen", "the h antigen in", "h antigen in non", "antigen in non secretors.", "in non secretors. type", "non secretors. type 1", "secretors. type 1 chains", "1 chains are found", "chains are found in", "are found in secretors.", "found in secretors. the", "in secretors. the se", "secretors. the se gene", "the se gene expressed", "se gene expressed in", "gene expressed in secretory", "expressed in secretory glands", "in secretory glands produces", "secretory glands produces \u03b1", "glands produces \u03b1 1", "1 2 fucosyltransferase 2", "fucosyltransferase 2 fut2", "fut2 which adds", "fucose to type 1", "to type 1 chains", "type 1 chains to", "1 chains to form", "h antigen in secretors.

              the", "antigen in secretors.

              the h", "in secretors.

              the h antigen", "secretors.

              the h antigen is", "h antigen is abundant", "antigen is abundant in", "is abundant in individuals", "abundant in individuals with", "in individuals with blood", "individuals with blood group", "with blood group o", "blood group o and", "group o and is", "o and is the", "and is the essential", "is the essential precursor", "the essential precursor for", "essential precursor for the", "precursor for the production", "for the production of", "the production of a", "production of a and", "of a and b", "a and b antigens.", "and b antigens. a", "b antigens. a and", "antigens. a and b", "and b antigens are", "b antigens are formed", "antigens are formed by", "are formed by the", "formed by the action", "by the action of", "the action of glycosyltransferases", "action of glycosyltransferases encoded", "of glycosyltransferases encoded by", "glycosyltransferases encoded by functional", "encoded by functional alleles", "by functional alleles at", "functional alleles at the", "alleles at the abo", "at the abo genetic", "the abo genetic locus.", "abo genetic locus. the", "genetic locus. the co", "locus. the co dominant", "the co dominant a", "co dominant a allele", "dominant a allele encodes", "a allele encodes a", "allele encodes a transferase", "a transferase which", "transferase which transfers", "which transfers an n", "transfers an n acetylgalactosamine", "n acetylgalactosamine galnac", "galnac sugar to", "sugar to the h", "to the h antigen", "the h antigen forming", "h antigen forming the", "antigen forming the a", "forming the a antigen.", "the a antigen. similarly", "antigen. similarly the", "similarly the co", "the co dominant b", "co dominant b allele", "dominant b allele encodes", "b allele encodes b", "allele encodes b transferase", "b transferase which", "which transfers a galactose", "a galactose gal", "gal sugar to", "antigen forming the b", "forming the b antigen.", "the b antigen. individuals", "b antigen. individuals who", "antigen. individuals who have", "individuals who have both", "who have both a", "have both a and", "both a and b", "a and b alleles", "and b alleles form", "b alleles form the", "alleles form the ab", "form the ab antigen.", "the ab antigen. individuals", "ab antigen. individuals who", "antigen. individuals who are", "individuals who are homozygous", "who are homozygous for", "are homozygous for the", "homozygous for the recessive", "for the recessive o", "the recessive o allele", "recessive o allele express", "o allele express the", "allele express the h", "express the h antigen", "the h antigen but", "h antigen but do", "antigen but do not", "but do not form", "do not form a", "not form a or", "form a or b", "a or b antigens", "or b antigens as", "b antigens as they", "antigens as they lack", "as they lack both", "they lack both the", "lack both the glycosyltransferase", "both the glycosyltransferase enzymes", "the glycosyltransferase enzymes for", "glycosyltransferase enzymes for their", "enzymes for their formation.", "for their formation. mutant", "their formation. mutant alleles", "formation. mutant alleles of", "mutant alleles of the", "alleles of the corresponding", "of the corresponding fut1", "the corresponding fut1 or", "corresponding fut1 or fut2", "fut1 or fut2 genes", "or fut2 genes result", "fut2 genes result in", "genes result in either", "result in either a", "in either a h\u2013", "either a h\u2013 phenotype", "h\u2013 phenotype bombay", "phenotype bombay phenotype", "bombay phenotype oh", "oh or a", "or a weak h", "a weak h phenotype", "h phenotype para", "phenotype para bombay", "para bombay where", "bombay where the", "where the affected individual", "the affected individual cannot", "affected individual cannot form", "individual cannot form h", "form h a", "h a or", "b antigens kaneko", "antigens kaneko et", "kaneko et al. 1997", "al. 1997 koda", "1997 koda et", "koda et al. 1997", "et al. 1997 .", "al. 1997 . the", "1997 . the biosyntheses", ". the biosyntheses of", "the biosyntheses of the", "biosyntheses of the a", "the a b", "b and h antigens", "and h antigens are", "h antigens are described", "antigens are described in", "are described in this", "described in this section", "this section ewald", "section ewald &", "ewald & sumner 2016", "sumner 2016 scharberg", "2016 scharberg et", "scharberg et al. 2016", "et al. 2016 .
              ", "perhaps the most important and", "the most important and widely", "most important and widely studied", "important and widely studied blood", "and widely studied blood group", "widely studied blood group is", "studied blood group is the", "blood group is the abo", "group is the abo blood", "is the abo blood group.", "the abo blood group. it", "abo blood group. it consists", "blood group. it consists of", "group. it consists of antigens", "it consists of antigens found", "consists of antigens found on", "of antigens found on the", "antigens found on the outer", "found on the outer surface", "on the outer surface of", "the outer surface of red", "outer surface of red cells", "surface of red cells and", "of red cells and corresponding", "red cells and corresponding antibodies", "cells and corresponding antibodies in", "and corresponding antibodies in plasma.", "corresponding antibodies in plasma. the", "antibodies in plasma. the majority", "in plasma. the majority of", "plasma. the majority of the", "the majority of the world's", "majority of the world's population", "the world's population ~80%", "population ~80% are", "~80% are 'secretors' which", "are 'secretors' which means that", "'secretors' which means that the", "which means that the antigens", "means that the antigens present", "that the antigens present in", "the antigens present in their", "antigens present in their blood", "present in their blood will", "in their blood will also", "their blood will also be", "blood will also be found", "will also be found in", "also be found in other", "be found in other body", "found in other body fluids", "in other body fluids such", "other body fluids such as", "body fluids such as saliva.", "fluids such as saliva. an", "such as saliva. an individual", "as saliva. an individual can", "saliva. an individual can be", "an individual can be a", "individual can be a secretor", "be a secretor se", "secretor se or", "se or a non", "a non secretor se", "secretor se and", "se and this is", "and this is completely independent", "this is completely independent of", "is completely independent of whether", "completely independent of whether the", "independent of whether the individual", "of whether the individual is", "whether the individual is of", "the individual is of blood", "individual is of blood type", "is of blood type a", "blood type a b", "a b ab", "b ab or", "ab or o. from", "or o. from a very", "o. from a very early", "from a very early age", "very early age the", "early age the immune", "age the immune system", "the immune system develops antibodies", "immune system develops antibodies against", "system develops antibodies against whichever", "develops antibodies against whichever abo", "antibodies against whichever abo blood", "against whichever abo blood group", "whichever abo blood group antigens", "abo blood group antigens are", "blood group antigens are not", "group antigens are not found", "antigens are not found on", "are not found on the", "not found on the individual's", "found on the individual's rbcs.", "on the individual's rbcs. thus", "individual's rbcs. thus a", "rbcs. thus a blood", "thus a blood group", "a blood group a individual", "blood group a individual will", "group a individual will have", "a individual will have anti", "individual will have anti b", "will have anti b antibodies", "have anti b antibodies and", "anti b antibodies and a", "b antibodies and a blood", "antibodies and a blood group", "and a blood group b", "a blood group b individual", "blood group b individual will", "group b individual will have", "b individual will have anti", "individual will have anti a", "will have anti a antibodies.", "have anti a antibodies. individuals", "anti a antibodies. individuals with", "a antibodies. individuals with the", "antibodies. individuals with the most", "individuals with the most common", "with the most common blood", "the most common blood group", "common blood group o", "o will have", "will have both anti a", "have both anti a and", "both anti a and anti", "anti a and anti b", "a and anti b in", "and anti b in their", "anti b in their plasma.", "b in their plasma. blood", "in their plasma. blood group", "their plasma. blood group ab", "plasma. blood group ab is", "blood group ab is the", "group ab is the least", "ab is the least common", "the least common and", "least common and these", "common and these individuals", "and these individuals will have", "these individuals will have neither", "individuals will have neither anti", "will have neither anti a", "have neither anti a nor", "neither anti a nor anti", "anti a nor anti b", "a nor anti b in", "nor anti b in their", "anti b in their plasma.

              the", "b in their plasma.

              the primary", "in their plasma.

              the primary structure", "their plasma.

              the primary structure of", "plasma.

              the primary structure of these", "primary structure of these antigens", "structure of these antigens is", "of these antigens is an", "these antigens is an oligosaccharide", "antigens is an oligosaccharide precursor", "is an oligosaccharide precursor sequence", "an oligosaccharide precursor sequence on", "oligosaccharide precursor sequence on to", "precursor sequence on to which", "sequence on to which one", "on to which one or", "to which one or more", "which one or more sugars", "one or more sugars are", "or more sugars are attached", "more sugars are attached at", "sugars are attached at specific", "are attached at specific locations.", "attached at specific locations. the", "at specific locations. the blood", "specific locations. the blood group", "locations. the blood group oligosaccharide", "the blood group oligosaccharide antigens", "blood group oligosaccharide antigens a", "oligosaccharide antigens a b", "antigens a b and", "a b and h", "b and h are produced", "and h are produced by", "h are produced by enzymes", "are produced by enzymes expressed", "produced by enzymes expressed by", "by enzymes expressed by these", "enzymes expressed by these genes", "expressed by these genes and", "by these genes and form", "these genes and form the", "genes and form the basis", "and form the basis of", "form the basis of the", "the basis of the abo", "basis of the abo 'blood", "of the abo 'blood type'", "the abo 'blood type' phenotypes.", "abo 'blood type' phenotypes. a", "'blood type' phenotypes. a and", "type' phenotypes. a and b", "phenotypes. a and b antigens", "a and b antigens were", "and b antigens were originally", "b antigens were originally identified", "antigens were originally identified on", "were originally identified on red", "originally identified on red blood", "identified on red blood cells", "red blood cells rbcs", "cells rbcs but", "rbcs but later identified", "but later identified on other", "later identified on other cell", "identified on other cell types", "on other cell types and", "other cell types and in", "cell types and in bodily", "types and in bodily secretions.", "and in bodily secretions. the", "in bodily secretions. the abo", "bodily secretions. the abo blood", "secretions. the abo blood group", "the abo blood group system", "abo blood group system is", "blood group system is important", "group system is important in", "system is important in blood", "is important in blood transfusion", "in blood transfusion cell/tissue/organ", "blood transfusion cell/tissue/organ transplantation", "transfusion cell/tissue/organ transplantation and", "cell/tissue/organ transplantation and forensic evidence", "transplantation and forensic evidence at", "and forensic evidence at crime", "forensic evidence at crime scenes.

              the", "evidence at crime scenes.

              the h", "at crime scenes.

              the h antigen", "crime scenes.

              the h antigen is", "scenes.

              the h antigen is formed", "h antigen is formed with", "antigen is formed with the", "is formed with the addition", "formed with the addition of", "with the addition of a", "the addition of a fucose", "addition of a fucose sugar", "of a fucose sugar onto", "a fucose sugar onto one", "fucose sugar onto one of", "sugar onto one of two", "onto one of two precursor", "one of two precursor oligosaccharide", "of two precursor oligosaccharide sequences", "precursor oligosaccharide sequences type", "oligosaccharide sequences type 1", "sequences type 1 chains", "type 1 chains are gal", "1 chains are gal \u03b21", "chains are gal \u03b21 3", "are gal \u03b21 3 glcnac", "gal \u03b21 3 glcnac \u03b21", "\u03b21 3 glcnac \u03b21 3", "3 glcnac \u03b21 3 gal", "glcnac \u03b21 3 gal r", "\u03b21 3 gal r and", "3 gal r and type", "gal r and type 2", "r and type 2 chains", "and type 2 chains are", "type 2 chains are gal", "2 chains are gal \u03b21", "chains are gal \u03b21 4", "are gal \u03b21 4 glcnac", "gal \u03b21 4 glcnac \u03b21", "\u03b21 4 glcnac \u03b21 3", "4 glcnac \u03b21 3 gal", "3 gal r where", "gal r where r", "r where r is", "where r is a glycoprotein", "is a glycoprotein type", "a glycoprotein type 1", "type 1 or glycosphingolipid", "or glycosphingolipid type 2", "glycosphingolipid type 2 .", "type 2 . type 2", "2 . type 2 chains", ". type 2 chains are", "type 2 chains are only", "2 chains are only found", "chains are only found on", "are only found on rbcs", "found on rbcs epithelial", "on rbcs epithelial cells", "rbcs epithelial cells and", "epithelial cells and endothelial cells.", "cells and endothelial cells. the", "and endothelial cells. the h", "endothelial cells. the h gene", "cells. the h gene expressed", "the h gene expressed in", "h gene expressed in hematopoietic", "gene expressed in hematopoietic cells", "expressed in hematopoietic cells produces", "in hematopoietic cells produces \u03b1", "hematopoietic cells produces \u03b1 1", "cells produces \u03b1 1 2", "produces \u03b1 1 2 fucosyltransferase", "\u03b1 1 2 fucosyltransferase 1", "2 fucosyltransferase 1 fut1", "1 fut1 which", "fut1 which adds a", "which adds a fucose to", "adds a fucose to type", "a fucose to type 2", "fucose to type 2 chains", "to type 2 chains to", "type 2 chains to form", "2 chains to form the", "chains to form the h", "to form the h antigen", "form the h antigen in", "the h antigen in non", "h antigen in non secretors.", "antigen in non secretors. type", "in non secretors. type 1", "non secretors. type 1 chains", "secretors. type 1 chains are", "type 1 chains are found", "1 chains are found in", "chains are found in secretors.", "are found in secretors. the", "found in secretors. the se", "in secretors. the se gene", "secretors. the se gene expressed", "the se gene expressed in", "se gene expressed in secretory", "gene expressed in secretory glands", "expressed in secretory glands produces", "in secretory glands produces \u03b1", "secretory glands produces \u03b1 1", "glands produces \u03b1 1 2", "\u03b1 1 2 fucosyltransferase 2", "2 fucosyltransferase 2 fut2", "2 fut2 which", "fut2 which adds a", "a fucose to type 1", "fucose to type 1 chains", "to type 1 chains to", "type 1 chains to form", "1 chains to form the", "the h antigen in secretors.

              the", "h antigen in secretors.

              the h", "antigen in secretors.

              the h antigen", "in secretors.

              the h antigen is", "secretors.

              the h antigen is abundant", "h antigen is abundant in", "antigen is abundant in individuals", "is abundant in individuals with", "abundant in individuals with blood", "in individuals with blood group", "individuals with blood group o", "with blood group o and", "blood group o and is", "group o and is the", "o and is the essential", "and is the essential precursor", "is the essential precursor for", "the essential precursor for the", "essential precursor for the production", "precursor for the production of", "for the production of a", "the production of a and", "production of a and b", "of a and b antigens.", "a and b antigens. a", "and b antigens. a and", "b antigens. a and b", "antigens. a and b antigens", "a and b antigens are", "and b antigens are formed", "b antigens are formed by", "antigens are formed by the", "are formed by the action", "formed by the action of", "by the action of glycosyltransferases", "the action of glycosyltransferases encoded", "action of glycosyltransferases encoded by", "of glycosyltransferases encoded by functional", "glycosyltransferases encoded by functional alleles", "encoded by functional alleles at", "by functional alleles at the", "functional alleles at the abo", "alleles at the abo genetic", "at the abo genetic locus.", "the abo genetic locus. the", "abo genetic locus. the co", "genetic locus. the co dominant", "locus. the co dominant a", "the co dominant a allele", "co dominant a allele encodes", "dominant a allele encodes a", "a allele encodes a transferase", "encodes a transferase which", "a transferase which transfers", "transferase which transfers an", "which transfers an n acetylgalactosamine", "an n acetylgalactosamine galnac", "acetylgalactosamine galnac sugar", "galnac sugar to the", "sugar to the h antigen", "to the h antigen forming", "the h antigen forming the", "h antigen forming the a", "antigen forming the a antigen.", "forming the a antigen. similarly", "a antigen. similarly the", "antigen. similarly the co", "similarly the co dominant", "the co dominant b allele", "co dominant b allele encodes", "dominant b allele encodes b", "b allele encodes b transferase", "encodes b transferase which", "b transferase which transfers", "transferase which transfers a", "transfers a galactose gal", "galactose gal sugar", "gal sugar to the", "h antigen forming the b", "antigen forming the b antigen.", "forming the b antigen. individuals", "the b antigen. individuals who", "b antigen. individuals who have", "antigen. individuals who have both", "individuals who have both a", "who have both a and", "have both a and b", "both a and b alleles", "a and b alleles form", "and b alleles form the", "b alleles form the ab", "alleles form the ab antigen.", "form the ab antigen. individuals", "the ab antigen. individuals who", "ab antigen. individuals who are", "antigen. individuals who are homozygous", "individuals who are homozygous for", "who are homozygous for the", "are homozygous for the recessive", "homozygous for the recessive o", "for the recessive o allele", "the recessive o allele express", "recessive o allele express the", "o allele express the h", "allele express the h antigen", "express the h antigen but", "the h antigen but do", "h antigen but do not", "antigen but do not form", "but do not form a", "do not form a or", "not form a or b", "form a or b antigens", "a or b antigens as", "or b antigens as they", "b antigens as they lack", "antigens as they lack both", "as they lack both the", "they lack both the glycosyltransferase", "lack both the glycosyltransferase enzymes", "both the glycosyltransferase enzymes for", "the glycosyltransferase enzymes for their", "glycosyltransferase enzymes for their formation.", "enzymes for their formation. mutant", "for their formation. mutant alleles", "their formation. mutant alleles of", "formation. mutant alleles of the", "mutant alleles of the corresponding", "alleles of the corresponding fut1", "of the corresponding fut1 or", "the corresponding fut1 or fut2", "corresponding fut1 or fut2 genes", "fut1 or fut2 genes result", "or fut2 genes result in", "fut2 genes result in either", "genes result in either a", "result in either a h\u2013", "in either a h\u2013 phenotype", "a h\u2013 phenotype bombay", "h\u2013 phenotype bombay phenotype", "phenotype oh or", "oh or a weak", "or a weak h phenotype", "weak h phenotype para", "h phenotype para bombay", "para bombay where the", "bombay where the affected", "where the affected individual cannot", "the affected individual cannot form", "affected individual cannot form h", "cannot form h a", "form h a or", "h a or b", "or b antigens kaneko", "b antigens kaneko et", "antigens kaneko et al.", "et al. 1997 koda", "al. 1997 koda et", "1997 koda et al.", "koda et al. 1997 .", "et al. 1997 . the", "al. 1997 . the biosyntheses", "1997 . the biosyntheses of", ". the biosyntheses of the", "the biosyntheses of the a", "of the a b", "the a b and", "b and h antigens are", "and h antigens are described", "h antigens are described in", "antigens are described in this", "are described in this section", "in this section ewald", "this section ewald &", "section ewald & sumner", "& sumner 2016 scharberg", "sumner 2016 scharberg et", "2016 scharberg et al.", "scharberg et al. 2016 .
              " ] }, { "record_id": "GLY_000594_1_1546", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9034013", "r hsa", "hsa 9034013", "r hsa 9034013" ] }, { "record_id": "GLY_000594_1_1546", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ntf3 activates", "activates ntrk3", "ntrk3 signaling", "ntf3 activates ntrk3", "activates ntrk3 signaling", "ntf3 activates ntrk3 signaling", "is activated", "activated by", "by binding", "binding to", "to its", "its ligand", "ligand neurotrophin", "neurotrophin 3", "also known", "known as", "as nt", "nt 3", "3 .", ". ligand", "ligand binding", "binding induces", "induces dimerization", "dimerization of", "of ntrk3", "ntrk3 and", "and trans", "trans autophosphorylation", "autophosphorylation of", "of dimerized", "dimerized receptors", "receptors on", "on conserved", "conserved tyrosine", "tyrosine residues", "residues in", "in the", "the cytoplasmic", "cytoplasmic tail.", "tail. autophosphorylated", "autophosphorylated tyrosines", "tyrosines serve", "serve as", "as docking", "docking sites", "sites for", "for binding", "binding of", "of adaptor", "adaptor proteins", "proteins that", "that mediate", "mediate downstream", "downstream signaling", "lamballe et", "et al.", "al. 1991", "philo et", "al. 1994", "tsoulfas et", "al. 1996", "huang and", "and reichardt", "reichardt 2001", "werner et", "al. 2014", "2014 .", "ntrk3 trkc", "trkc is", "is activated by", "activated by binding", "by binding to", "binding to its", "to its ligand", "its ligand neurotrophin", "ligand neurotrophin 3", "3 ntf3", "ntf3 also", "also known as", "known as nt", "as nt 3", "nt 3 .", "3 . ligand", ". ligand binding", "ligand binding induces", "binding induces dimerization", "induces dimerization of", "dimerization of ntrk3", "of ntrk3 and", "ntrk3 and trans", "and trans autophosphorylation", "trans autophosphorylation of", "autophosphorylation of dimerized", "of dimerized receptors", "dimerized receptors on", "receptors on conserved", "on conserved tyrosine", "conserved tyrosine residues", "tyrosine residues in", "residues in the", "in the cytoplasmic", "the cytoplasmic tail.", "cytoplasmic tail. autophosphorylated", "tail. autophosphorylated tyrosines", "autophosphorylated tyrosines serve", "tyrosines serve as", "serve as docking", "as docking sites", "docking sites for", "sites for binding", "for binding of", "binding of adaptor", "of adaptor proteins", "adaptor proteins that", "proteins that mediate", "that mediate downstream", "mediate downstream signaling", "signaling lamballe", "lamballe et al.", "et al. 1991", "1991 philo", "philo et al.", "et al. 1994", "1994 tsoulfas", "tsoulfas et al.", "et al. 1996", "1996 huang", "huang and reichardt", "and reichardt 2001", "2001 werner", "werner et al.", "et al. 2014", "al. 2014 .", "trkc is activated", "is activated by binding", "activated by binding to", "by binding to its", "binding to its ligand", "to its ligand neurotrophin", "its ligand neurotrophin 3", "neurotrophin 3 ntf3", "ntf3 also known", "also known as nt", "known as nt 3", "as nt 3 .", "nt 3 . ligand", "3 . ligand binding", ". ligand binding induces", "ligand binding induces dimerization", "binding induces dimerization of", "induces dimerization of ntrk3", "dimerization of ntrk3 and", "of ntrk3 and trans", "ntrk3 and trans autophosphorylation", "and trans autophosphorylation of", "trans autophosphorylation of dimerized", "autophosphorylation of dimerized receptors", "of dimerized receptors on", "dimerized receptors on conserved", "receptors on conserved tyrosine", "on conserved tyrosine residues", "conserved tyrosine residues in", "tyrosine residues in the", "residues in the cytoplasmic", "in the cytoplasmic tail.", "the cytoplasmic tail. autophosphorylated", "cytoplasmic tail. autophosphorylated tyrosines", "tail. autophosphorylated tyrosines serve", "autophosphorylated tyrosines serve as", "tyrosines serve as docking", "serve as docking sites", "as docking sites for", "docking sites for binding", "sites for binding of", "for binding of adaptor", "binding of adaptor proteins", "of adaptor proteins that", "adaptor proteins that mediate", "proteins that mediate downstream", "that mediate downstream signaling", "downstream signaling lamballe", "signaling lamballe et", "lamballe et al. 1991", "al. 1991 philo", "1991 philo et", "philo et al. 1994", "al. 1994 tsoulfas", "1994 tsoulfas et", "tsoulfas et al. 1996", "al. 1996 huang", "1996 huang and", "huang and reichardt 2001", "reichardt 2001 werner", "2001 werner et", "werner et al. 2014", "et al. 2014 .", "ntrk3 trkc is", "trkc is activated by", "is activated by binding to", "activated by binding to its", "by binding to its ligand", "binding to its ligand neurotrophin", "to its ligand neurotrophin 3", "ligand neurotrophin 3 ntf3", "3 ntf3 also", "ntf3 also known as", "also known as nt 3", "known as nt 3 .", "as nt 3 . ligand", "nt 3 . ligand binding", "3 . ligand binding induces", ". ligand binding induces dimerization", "ligand binding induces dimerization of", "binding induces dimerization of ntrk3", "induces dimerization of ntrk3 and", "dimerization of ntrk3 and trans", "of ntrk3 and trans autophosphorylation", "ntrk3 and trans autophosphorylation of", "and trans autophosphorylation of dimerized", "trans autophosphorylation of dimerized receptors", "autophosphorylation of dimerized receptors on", "of dimerized receptors on conserved", "dimerized receptors on conserved tyrosine", "receptors on conserved tyrosine residues", "on conserved tyrosine residues in", "conserved tyrosine residues in the", "tyrosine residues in the cytoplasmic", "residues in the cytoplasmic tail.", "in the cytoplasmic tail. autophosphorylated", "the cytoplasmic tail. autophosphorylated tyrosines", "cytoplasmic tail. autophosphorylated tyrosines serve", "tail. autophosphorylated tyrosines serve as", "autophosphorylated tyrosines serve as docking", "tyrosines serve as docking sites", "serve as docking sites for", "as docking sites for binding", "docking sites for binding of", "sites for binding of adaptor", "for binding of adaptor proteins", "binding of adaptor proteins that", "of adaptor proteins that mediate", "adaptor proteins that mediate downstream", "proteins that mediate downstream signaling", "mediate downstream signaling lamballe", "downstream signaling lamballe et", "signaling lamballe et al.", "et al. 1991 philo", "al. 1991 philo et", "1991 philo et al.", "et al. 1994 tsoulfas", "al. 1994 tsoulfas et", "1994 tsoulfas et al.", "et al. 1996 huang", "al. 1996 huang and", "1996 huang and reichardt", "and reichardt 2001 werner", "reichardt 2001 werner et", "2001 werner et al.", "werner et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1547", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9034015", "r hsa", "hsa 9034015", "r hsa 9034015" ] }, { "record_id": "GLY_000594_1_1547", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by ntrk3", "signaling by ntrk3", "ntrk3 trkc", "by ntrk3 trkc", "signaling by ntrk3 trkc", "belongs to", "to the", "the family", "family of", "of neurotrophin", "neurotrophin receptor", "receptor tyrosine", "tyrosine kinases", "which also", "also includes", "includes ntrk1", "and ntrk2", "trkb .", ". neurotrophin", "neurotrophin 3", "also known", "known as", "as nt", "nt 3", "is the", "the ligand", "ligand for", "for ntrk3.", "ntrk3. similar", "similar to", "to other", "other ntrk", "ntrk receptors", "receptors and", "and receptor", "kinases in", "in general", "ligand binding", "binding induces", "induces receptor", "receptor dimerization", "dimerization followed", "followed by", "by trans", "trans autophosphorylation", "autophosphorylation on", "on conserved", "conserved tyrosines", "tyrosines in", "in the", "the intracellular", "domain of", "of the", "the receptor", "lamballe et", "et al.", "al. 1991", "philo et", "al. 1994", "tsoulfas et", "al. 1996", "yuen and", "and mobley", "mobley 1999", "werner et", "al. 2014", "2014 .", ". these", "these conserved", "tyrosines serve", "serve as", "as docking", "docking sites", "sites for", "for adaptor", "adaptor proteins", "proteins that", "that trigger", "trigger downstream", "downstream signaling", "signaling cascades.", "cascades. signaling", "signaling through", "through plcg1", "marsh and", "and palfrey", "palfrey 1996", "huang and", "and reichardt", "reichardt 2001", "tognon et", "al. 2001", "morrison et", "al. 2002", "lannon et", "al. 2004", "jin et", "al. 2008", "and ras", "gunn moore", "moore et", "al. 1997", "gromnitza et", "al. 2018", "downstream of", "of activated", "activated ntrk3", "regulates cell", "cell survival", "proliferation and", "and motility.

              in", "motility.

              in the", "the absence", "absence of", "of its", "its ligand", "ntrk3 functions", "functions as", "as a", "a dependence", "dependence receptor", "receptor and", "and triggers", "triggers bax", "bax and", "and casp9", "casp9 dependent", "dependent cell", "cell death", "tauszig delamasure", "delamasure et", "al. 2007", "ichim et", "al. 2013", "2013 .

              ntrk3", ".

              ntrk3 was", "was reported", "reported to", "to activate", "activate stat3", "stat3 through", "through jak2", "but the", "the exact", "exact mechanism", "mechanism has", "has not", "not been", "been elucidated", "kim et", "al. 2016", "2016 .", ". ntrk3", "ntrk3 was", "to interact", "interact with", "with the", "the adaptor", "adaptor protein", "protein sh2b2", "the biological", "biological role", "role of", "of this", "this interaction", "interaction has", "been determined", "qian et", "al. 1998", "1998 .

              receptor", ".

              receptor protein", "protein tyrosine", "tyrosine phosphatases", "phosphatases ptpro", "ptpro and", "and ptprs", "negatively regulate", "regulate ntrk3", "ntrk3 signaling", "by dephosphorylating", "dephosphorylating ntrk3", "beltran et", "al. 2003", "faux et", "hower et", "al. 2009", "tchetchelnitski et", ". in", "in addition", "addition to", "to dephosphorylation", "dephosphorylation of", "of ntrk3", "ntrk3 in", "in cis", "the extracellular", "extracellular domain", "of pre", "pre synaptic", "synaptic ptprs", "ptprs can", "can bind", "bind in", "in trans", "trans to", "to extracellular", "of post", "post synaptic", "synaptic ntrk3", "contributing to", "to synapse", "synapse formation", "takahashi et", "al. 2011", "coles et", "trkc belongs", "belongs to the", "to the family", "the family of", "family of neurotrophin", "of neurotrophin receptor", "neurotrophin receptor tyrosine", "receptor tyrosine kinases", "kinases which", "which also includes", "also includes ntrk1", "ntrk1 trka", "trka and", "ntrk2 trkb", "trkb . neurotrophin", ". neurotrophin 3", "3 ntf3", "ntf3 also", "also known as", "known as nt", "as nt 3", "3 is", "is the ligand", "the ligand for", "ligand for ntrk3.", "for ntrk3. similar", "ntrk3. similar to", "similar to other", "to other ntrk", "other ntrk receptors", "ntrk receptors and", "receptors and receptor", "and receptor tyrosine", "tyrosine kinases in", "kinases in general", "general ligand", "ligand binding induces", "binding induces receptor", "induces receptor dimerization", "receptor dimerization followed", "dimerization followed by", "followed by trans", "by trans autophosphorylation", "trans autophosphorylation on", "autophosphorylation on conserved", "on conserved tyrosines", "conserved tyrosines in", "tyrosines in the", "in the intracellular", "intracellular cytoplasmic", "cytoplasmic domain", "domain of the", "of the receptor", "receptor lamballe", "lamballe et al.", "et al. 1991", "1991 philo", "philo et al.", "et al. 1994", "1994 tsoulfas", "tsoulfas et al.", "et al. 1996", "1996 yuen", "yuen and mobley", "and mobley 1999", "1999 werner", "werner et al.", "et al. 2014", "al. 2014 .", "2014 . these", ". these conserved", "these conserved tyrosines", "conserved tyrosines serve", "tyrosines serve as", "serve as docking", "as docking sites", "docking sites for", "sites for adaptor", "for adaptor proteins", "adaptor proteins that", "proteins that trigger", "that trigger downstream", "trigger downstream signaling", "downstream signaling cascades.", "signaling cascades. signaling", "cascades. signaling through", "signaling through plcg1", "plcg1 marsh", "marsh and palfrey", "and palfrey 1996", "1999 huang", "huang and reichardt", "and reichardt 2001", "pi3k yuen", "1999 tognon", "tognon et al.", "et al. 2001", "2001 huang", "2001 morrison", "morrison et al.", "et al. 2002", "2002 lannon", "lannon et al.", "et al. 2004", "2004 jin", "jin et al.", "et al. 2008", "2008 and", "ras marsh", "1996 gunn", "gunn moore et", "moore et al.", "et al. 1997", "1997 yuen", "1999 gromnitza", "gromnitza et al.", "et al. 2018", "downstream of activated", "of activated ntrk3", "ntrk3 regulates", "regulates cell survival", "survival proliferation", "proliferation and motility.

              in", "and motility.

              in the", "motility.

              in the absence", "the absence of", "absence of its", "of its ligand", "ligand ntrk3", "ntrk3 functions as", "functions as a", "as a dependence", "a dependence receptor", "dependence receptor and", "receptor and triggers", "and triggers bax", "triggers bax and", "bax and casp9", "and casp9 dependent", "casp9 dependent cell", "dependent cell death", "death tauszig", "tauszig delamasure et", "delamasure et al.", "et al. 2007", "2007 ichim", "ichim et al.", "et al. 2013", "al. 2013 .

              ntrk3", "2013 .

              ntrk3 was", ".

              ntrk3 was reported", "was reported to", "reported to activate", "to activate stat3", "activate stat3 through", "stat3 through jak2", "jak2 but", "but the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "has not been", "not been elucidated", "elucidated kim", "kim et al.", "et al. 2016", "al. 2016 .", "2016 . ntrk3", ". ntrk3 was", "ntrk3 was reported", "reported to interact", "to interact with", "interact with the", "with the adaptor", "the adaptor protein", "adaptor protein sh2b2", "sh2b2 but", "but the biological", "the biological role", "biological role of", "role of this", "of this interaction", "this interaction has", "interaction has not", "not been determined", "determined qian", "qian et al.", "et al. 1998", "al. 1998 .

              receptor", "1998 .

              receptor protein", ".

              receptor protein tyrosine", "protein tyrosine phosphatases", "tyrosine phosphatases ptpro", "phosphatases ptpro and", "ptpro and ptprs", "ptprs ptpsigma", "ptpsigma negatively", "negatively regulate ntrk3", "regulate ntrk3 signaling", "ntrk3 signaling by", "signaling by dephosphorylating", "by dephosphorylating ntrk3", "ntrk3 beltran", "beltran et al.", "et al. 2003", "2003 faux", "faux et al.", "2007 hower", "hower et al.", "et al. 2009", "2009 tchetchelnitski", "tchetchelnitski et al.", "2014 . in", ". in addition", "in addition to", "addition to dephosphorylation", "to dephosphorylation of", "dephosphorylation of ntrk3", "of ntrk3 in", "ntrk3 in cis", "cis the", "the extracellular domain", "extracellular domain of", "domain of pre", "of pre synaptic", "pre synaptic ptprs", "synaptic ptprs can", "ptprs can bind", "can bind in", "bind in trans", "in trans to", "trans to extracellular", "to extracellular domain", "domain of post", "of post synaptic", "post synaptic ntrk3", "ntrk3 contributing", "contributing to synapse", "to synapse formation", "formation takahashi", "takahashi et al.", "et al. 2011", "2011 coles", "coles et al.", "trkc belongs to", "belongs to the family", "to the family of", "the family of neurotrophin", "family of neurotrophin receptor", "of neurotrophin receptor tyrosine", "neurotrophin receptor tyrosine kinases", "tyrosine kinases which", "kinases which also", "which also includes ntrk1", "includes ntrk1 trka", "trka and ntrk2", "and ntrk2 trkb", "ntrk2 trkb .", "trkb . neurotrophin 3", "neurotrophin 3 ntf3", "ntf3 also known", "also known as nt", "known as nt 3", "nt 3 is", "3 is the", "is the ligand for", "the ligand for ntrk3.", "ligand for ntrk3. similar", "for ntrk3. similar to", "ntrk3. similar to other", "similar to other ntrk", "to other ntrk receptors", "other ntrk receptors and", "ntrk receptors and receptor", "receptors and receptor tyrosine", "and receptor tyrosine kinases", "receptor tyrosine kinases in", "tyrosine kinases in general", "in general ligand", "general ligand binding", "ligand binding induces receptor", "binding induces receptor dimerization", "induces receptor dimerization followed", "receptor dimerization followed by", "dimerization followed by trans", "followed by trans autophosphorylation", "by trans autophosphorylation on", "trans autophosphorylation on conserved", "autophosphorylation on conserved tyrosines", "on conserved tyrosines in", "conserved tyrosines in the", "tyrosines in the intracellular", "the intracellular cytoplasmic", "cytoplasmic domain of", "domain of the receptor", "the receptor lamballe", "receptor lamballe et", "lamballe et al. 1991", "al. 1991 philo", "1991 philo et", "philo et al. 1994", "al. 1994 tsoulfas", "1994 tsoulfas et", "tsoulfas et al. 1996", "al. 1996 yuen", "1996 yuen and", "yuen and mobley 1999", "mobley 1999 werner", "1999 werner et", "werner et al. 2014", "et al. 2014 .", "al. 2014 . these", "2014 . these conserved", ". these conserved tyrosines", "these conserved tyrosines serve", "conserved tyrosines serve as", "tyrosines serve as docking", "serve as docking sites", "as docking sites for", "docking sites for adaptor", "sites for adaptor proteins", "for adaptor proteins that", "adaptor proteins that trigger", "proteins that trigger downstream", "that trigger downstream signaling", "trigger downstream signaling cascades.", "downstream signaling cascades. signaling", "signaling cascades. signaling through", "cascades. signaling through plcg1", "through plcg1 marsh", "plcg1 marsh and", "marsh and palfrey 1996", "palfrey 1996 yuen", "mobley 1999 huang", "1999 huang and", "huang and reichardt 2001", "2001 pi3k", "pi3k yuen and", "mobley 1999 tognon", "1999 tognon et", "tognon et al. 2001", "al. 2001 huang", "2001 huang and", "reichardt 2001 morrison", "2001 morrison et", "morrison et al. 2002", "al. 2002 lannon", "2002 lannon et", "lannon et al. 2004", "al. 2004 jin", "2004 jin et", "jin et al. 2008", "al. 2008 and", "2008 and ras", "and ras marsh", "ras marsh and", "palfrey 1996 gunn", "1996 gunn moore", "gunn moore et al.", "moore et al. 1997", "al. 1997 yuen", "1997 yuen and", "mobley 1999 gromnitza", "1999 gromnitza et", "gromnitza et al. 2018", "2018 downstream", "downstream of activated ntrk3", "activated ntrk3 regulates", "ntrk3 regulates cell", "cell survival proliferation", "survival proliferation and", "proliferation and motility.

              in the", "and motility.

              in the absence", "motility.

              in the absence of", "the absence of its", "absence of its ligand", "its ligand ntrk3", "ligand ntrk3 functions", "ntrk3 functions as a", "functions as a dependence", "as a dependence receptor", "a dependence receptor and", "dependence receptor and triggers", "receptor and triggers bax", "and triggers bax and", "triggers bax and casp9", "bax and casp9 dependent", "and casp9 dependent cell", "casp9 dependent cell death", "cell death tauszig", "death tauszig delamasure", "tauszig delamasure et al.", "delamasure et al. 2007", "al. 2007 ichim", "2007 ichim et", "ichim et al. 2013", "et al. 2013 .

              ntrk3", "al. 2013 .

              ntrk3 was", "2013 .

              ntrk3 was reported", ".

              ntrk3 was reported to", "was reported to activate", "reported to activate stat3", "to activate stat3 through", "activate stat3 through jak2", "through jak2 but", "jak2 but the", "but the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been elucidated", "been elucidated kim", "elucidated kim et", "kim et al. 2016", "et al. 2016 .", "al. 2016 . ntrk3", "2016 . ntrk3 was", ". ntrk3 was reported", "ntrk3 was reported to", "was reported to interact", "reported to interact with", "to interact with the", "interact with the adaptor", "with the adaptor protein", "the adaptor protein sh2b2", "protein sh2b2 but", "sh2b2 but the", "but the biological role", "the biological role of", "biological role of this", "role of this interaction", "of this interaction has", "this interaction has not", "interaction has not been", "has not been determined", "been determined qian", "determined qian et", "qian et al. 1998", "et al. 1998 .

              receptor", "al. 1998 .

              receptor protein", "1998 .

              receptor protein tyrosine", ".

              receptor protein tyrosine phosphatases", "protein tyrosine phosphatases ptpro", "tyrosine phosphatases ptpro and", "phosphatases ptpro and ptprs", "and ptprs ptpsigma", "ptpsigma negatively regulate", "negatively regulate ntrk3 signaling", "regulate ntrk3 signaling by", "ntrk3 signaling by dephosphorylating", "signaling by dephosphorylating ntrk3", "dephosphorylating ntrk3 beltran", "ntrk3 beltran et", "beltran et al. 2003", "al. 2003 faux", "2003 faux et", "faux et al. 2007", "al. 2007 hower", "2007 hower et", "hower et al. 2009", "al. 2009 tchetchelnitski", "2009 tchetchelnitski et", "tchetchelnitski et al. 2014", "al. 2014 . in", "2014 . in addition", ". in addition to", "in addition to dephosphorylation", "addition to dephosphorylation of", "to dephosphorylation of ntrk3", "dephosphorylation of ntrk3 in", "of ntrk3 in cis", "in cis the", "cis the extracellular", "the extracellular domain of", "extracellular domain of pre", "domain of pre synaptic", "of pre synaptic ptprs", "pre synaptic ptprs can", "synaptic ptprs can bind", "ptprs can bind in", "can bind in trans", "bind in trans to", "in trans to extracellular", "trans to extracellular domain", "to extracellular domain of", "extracellular domain of post", "domain of post synaptic", "of post synaptic ntrk3", "synaptic ntrk3 contributing", "ntrk3 contributing to", "contributing to synapse formation", "synapse formation takahashi", "formation takahashi et", "takahashi et al. 2011", "al. 2011 coles", "2011 coles et", "coles et al. 2014", "ntrk3 trkc belongs", "trkc belongs to the", "belongs to the family of", "to the family of neurotrophin", "the family of neurotrophin receptor", "family of neurotrophin receptor tyrosine", "of neurotrophin receptor tyrosine kinases", "receptor tyrosine kinases which", "tyrosine kinases which also", "kinases which also includes", "also includes ntrk1 trka", "ntrk1 trka and", "and ntrk2 trkb .", "ntrk2 trkb . neurotrophin", ". neurotrophin 3 ntf3", "3 ntf3 also", "ntf3 also known as", "also known as nt 3", "as nt 3 is", "nt 3 is the", "3 is the ligand", "is the ligand for ntrk3.", "the ligand for ntrk3. similar", "ligand for ntrk3. similar to", "for ntrk3. similar to other", "ntrk3. similar to other ntrk", "similar to other ntrk receptors", "to other ntrk receptors and", "other ntrk receptors and receptor", "ntrk receptors and receptor tyrosine", "receptors and receptor tyrosine kinases", "and receptor tyrosine kinases in", "receptor tyrosine kinases in general", "kinases in general ligand", "in general ligand binding", "general ligand binding induces", "ligand binding induces receptor dimerization", "binding induces receptor dimerization followed", "induces receptor dimerization followed by", "receptor dimerization followed by trans", "dimerization followed by trans autophosphorylation", "followed by trans autophosphorylation on", "by trans autophosphorylation on conserved", "trans autophosphorylation on conserved tyrosines", "autophosphorylation on conserved tyrosines in", "on conserved tyrosines in the", "conserved tyrosines in the intracellular", "in the intracellular cytoplasmic", "intracellular cytoplasmic domain", "cytoplasmic domain of the", "of the receptor lamballe", "the receptor lamballe et", "receptor lamballe et al.", "et al. 1991 philo", "al. 1991 philo et", "1991 philo et al.", "et al. 1994 tsoulfas", "al. 1994 tsoulfas et", "1994 tsoulfas et al.", "et al. 1996 yuen", "al. 1996 yuen and", "1996 yuen and mobley", "and mobley 1999 werner", "mobley 1999 werner et", "1999 werner et al.", "werner et al. 2014 .", "et al. 2014 . these", "al. 2014 . these conserved", "2014 . these conserved tyrosines", ". these conserved tyrosines serve", "these conserved tyrosines serve as", "conserved tyrosines serve as docking", "tyrosines serve as docking sites", "serve as docking sites for", "as docking sites for adaptor", "docking sites for adaptor proteins", "sites for adaptor proteins that", "for adaptor proteins that trigger", "adaptor proteins that trigger downstream", "proteins that trigger downstream signaling", "that trigger downstream signaling cascades.", "trigger downstream signaling cascades. signaling", "downstream signaling cascades. signaling through", "signaling cascades. signaling through plcg1", "signaling through plcg1 marsh", "through plcg1 marsh and", "plcg1 marsh and palfrey", "and palfrey 1996 yuen", "palfrey 1996 yuen and", "and mobley 1999 huang", "mobley 1999 huang and", "1999 huang and reichardt", "reichardt 2001 pi3k", "pi3k yuen and mobley", "and mobley 1999 tognon", "mobley 1999 tognon et", "1999 tognon et al.", "et al. 2001 huang", "al. 2001 huang and", "2001 huang and reichardt", "and reichardt 2001 morrison", "reichardt 2001 morrison et", "2001 morrison et al.", "et al. 2002 lannon", "al. 2002 lannon et", "2002 lannon et al.", "et al. 2004 jin", "al. 2004 jin et", "2004 jin et al.", "et al. 2008 and", "al. 2008 and ras", "and ras marsh and", "ras marsh and palfrey", "and palfrey 1996 gunn", "palfrey 1996 gunn moore", "1996 gunn moore et", "gunn moore et al. 1997", "et al. 1997 yuen", "al. 1997 yuen and", "1997 yuen and mobley", "and mobley 1999 gromnitza", "mobley 1999 gromnitza et", "1999 gromnitza et al.", "al. 2018 downstream", "2018 downstream of", "of activated ntrk3 regulates", "activated ntrk3 regulates cell", "ntrk3 regulates cell survival", "regulates cell survival proliferation", "cell survival proliferation and", "survival proliferation and motility.

              in", "proliferation and motility.

              in the absence", "and motility.

              in the absence of", "motility.

              in the absence of its", "the absence of its ligand", "of its ligand ntrk3", "its ligand ntrk3 functions", "ligand ntrk3 functions as", "ntrk3 functions as a dependence", "functions as a dependence receptor", "as a dependence receptor and", "a dependence receptor and triggers", "dependence receptor and triggers bax", "receptor and triggers bax and", "and triggers bax and casp9", "triggers bax and casp9 dependent", "bax and casp9 dependent cell", "and casp9 dependent cell death", "dependent cell death tauszig", "cell death tauszig delamasure", "death tauszig delamasure et", "tauszig delamasure et al. 2007", "et al. 2007 ichim", "al. 2007 ichim et", "2007 ichim et al.", "ichim et al. 2013 .

              ntrk3", "et al. 2013 .

              ntrk3 was", "al. 2013 .

              ntrk3 was reported", "2013 .

              ntrk3 was reported to", ".

              ntrk3 was reported to activate", "was reported to activate stat3", "reported to activate stat3 through", "to activate stat3 through jak2", "stat3 through jak2 but", "through jak2 but the", "jak2 but the exact", "but the exact mechanism has", "the exact mechanism has not", "exact mechanism has not been", "mechanism has not been elucidated", "not been elucidated kim", "been elucidated kim et", "elucidated kim et al.", "kim et al. 2016 .", "et al. 2016 . ntrk3", "al. 2016 . ntrk3 was", "2016 . ntrk3 was reported", ". ntrk3 was reported to", "ntrk3 was reported to interact", "was reported to interact with", "reported to interact with the", "to interact with the adaptor", "interact with the adaptor protein", "with the adaptor protein sh2b2", "adaptor protein sh2b2 but", "protein sh2b2 but the", "sh2b2 but the biological", "but the biological role of", "the biological role of this", "biological role of this interaction", "role of this interaction has", "of this interaction has not", "this interaction has not been", "interaction has not been determined", "not been determined qian", "been determined qian et", "determined qian et al.", "qian et al. 1998 .

              receptor", "et al. 1998 .

              receptor protein", "al. 1998 .

              receptor protein tyrosine", "1998 .

              receptor protein tyrosine phosphatases", ".

              receptor protein tyrosine phosphatases ptpro", "protein tyrosine phosphatases ptpro and", "tyrosine phosphatases ptpro and ptprs", "ptpro and ptprs ptpsigma", "ptprs ptpsigma negatively", "ptpsigma negatively regulate ntrk3", "negatively regulate ntrk3 signaling by", "regulate ntrk3 signaling by dephosphorylating", "ntrk3 signaling by dephosphorylating ntrk3", "by dephosphorylating ntrk3 beltran", "dephosphorylating ntrk3 beltran et", "ntrk3 beltran et al.", "et al. 2003 faux", "al. 2003 faux et", "2003 faux et al.", "et al. 2007 hower", "al. 2007 hower et", "2007 hower et al.", "et al. 2009 tchetchelnitski", "al. 2009 tchetchelnitski et", "2009 tchetchelnitski et al.", "tchetchelnitski et al. 2014 .", "et al. 2014 . in", "al. 2014 . in addition", "2014 . in addition to", ". in addition to dephosphorylation", "in addition to dephosphorylation of", "addition to dephosphorylation of ntrk3", "to dephosphorylation of ntrk3 in", "dephosphorylation of ntrk3 in cis", "ntrk3 in cis the", "in cis the extracellular", "cis the extracellular domain", "the extracellular domain of pre", "extracellular domain of pre synaptic", "domain of pre synaptic ptprs", "of pre synaptic ptprs can", "pre synaptic ptprs can bind", "synaptic ptprs can bind in", "ptprs can bind in trans", "can bind in trans to", "bind in trans to extracellular", "in trans to extracellular domain", "trans to extracellular domain of", "to extracellular domain of post", "extracellular domain of post synaptic", "domain of post synaptic ntrk3", "post synaptic ntrk3 contributing", "synaptic ntrk3 contributing to", "ntrk3 contributing to synapse", "to synapse formation takahashi", "synapse formation takahashi et", "formation takahashi et al.", "et al. 2011 coles", "al. 2011 coles et", "2011 coles et al.", "coles et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1548", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9034793", "r hsa", "hsa 9034793", "r hsa 9034793" ] }, { "record_id": "GLY_000594_1_1548", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "activated ntrk3", "ntrk3 signals", "signals through", "through plcg1", "activated ntrk3 signals", "ntrk3 signals through", "signals through plcg1", "activated ntrk3 signals through", "ntrk3 signals through plcg1", "activated ntrk3 signals through plcg1", "the receptor", "receptor tyrosine", "tyrosine kinase", "kinase ntrk3", "when activated", "activated by", "by its", "its ligand", "ligand ntf3", "nt 3", "induces plcg1", "plcg1 phosphorylation", "triggering plcg1", "plcg1 signaling", "marsh and", "and palfrey", "palfrey 1996", "yuen and", "and mobley", "mobley 1999", "1999 .", "the receptor tyrosine", "receptor tyrosine kinase", "tyrosine kinase ntrk3", "ntrk3 trkc", "when activated by", "activated by its", "by its ligand", "its ligand ntf3", "ntf3 nt", "induces plcg1 phosphorylation", "phosphorylation triggering", "triggering plcg1 signaling", 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and", "signaling marsh and palfrey", "and palfrey 1996 yuen", "palfrey 1996 yuen and", "1996 yuen and mobley", "yuen and mobley 1999 ." ] }, { "record_id": "GLY_000594_1_1549", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9035968", "r hsa", "hsa 9035968", "r hsa 9035968" ] }, { "record_id": "GLY_000594_1_1549", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective ggt1", "ggt1 in", "in aflatoxin", "aflatoxin detoxification", "detoxification causes", "causes gluth", "defective ggt1 in", "ggt1 in aflatoxin", "in aflatoxin detoxification", "aflatoxin detoxification causes", "detoxification causes gluth", "defective ggt1 in aflatoxin", "ggt1 in aflatoxin detoxification", "in aflatoxin detoxification causes", "aflatoxin detoxification causes gluth", "defective ggt1 in aflatoxin detoxification", "ggt1 in aflatoxin detoxification causes", "in aflatoxin detoxification causes gluth", "to be", "be excreted", "excreted in", "in urine", "glutathione conjugates", "conjugates undergo", "undergo several", "several hydrolysis", "hydrolysis steps", "steps to", "to form", "form mercapturic", "mercapturic acids", "acids which", "which are", "are readily", "readily excreted.", "excreted. the", "the first", "first step", "step is", "is the", "the hydrolysis", "hydrolysis of", "of a", "a gamma", "gamma glutamyl", "glutamyl residue", "residue from", "from the", "the conjugate", "conjugate catalysed", "catalysed by", "by gamma", "gamma glutamyltransferases", "ggts .", ". these", "these are", "are membrane", "membrane bound", "heterodimeric enzymes", "enzymes composed", "composed of", "of light", "light and", "and heavy", "heavy peptide", "peptide chains.", "chains. extracellular", "extracellular glutathione", "or its", "its conjugates", "conjugates can", "can be", "be hydrolysed", "hydrolysed to", "to give", "give cysteinylglycine", "or cg", "cg conjugates", "and free", "free glutamate", "l 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"are readily excreted. the", "readily excreted. the first", "excreted. the first step", "the first step is", "first step is the", "step is the hydrolysis", "is the hydrolysis of", "the hydrolysis of a", "hydrolysis of a gamma", "of a gamma glutamyl", "a gamma glutamyl residue", "gamma glutamyl residue from", "glutamyl residue from the", "residue from the conjugate", "from the conjugate catalysed", "the conjugate catalysed by", "conjugate catalysed by gamma", "catalysed by gamma glutamyltransferases", "gamma glutamyltransferases ggts", "glutamyltransferases ggts .", "ggts . these are", ". these are membrane", "these are membrane bound", "membrane bound heterodimeric", "bound heterodimeric enzymes", "heterodimeric enzymes composed of", "enzymes composed of light", "composed of light and", "of light and heavy", "light and heavy peptide", "and heavy peptide chains.", "heavy peptide chains. extracellular", "peptide chains. extracellular glutathione", "extracellular glutathione gsh", "gsh or 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glutathionuria gluth", "mim:231950 an", "231950 an", "an autosomal recessive disorder", "autosomal recessive disorder characterised", "recessive disorder characterised by", "disorder characterised by increased", "characterised by increased gsh", "by increased gsh concentration", "increased gsh concentration in", "gsh concentration in the", "concentration in the plasma", "in the plasma and", "the plasma and urine.", "plasma and urine. mutations", "and urine. mutations that", "urine. mutations that cause", "mutations that cause gluth", "that cause gluth can", "cause gluth can occur", "gluth can occur in", "can occur in both", "occur in both chains", "in both chains of", "both chains of the", "chains of the ggt1", "of the ggt1 dimer", "ggt1 dimer heisterkamp", "dimer heisterkamp et", "al. 2008 aoyama", "2008 aoyama &", "aoyama & nakaki 2013", "& nakaki 2013 .", "to be excreted in urine", "excreted in urine glutathione", "in urine glutathione conjugates", "urine glutathione conjugates 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glutamyltransferases", "by gamma glutamyltransferases ggts", "gamma glutamyltransferases ggts .", "glutamyltransferases ggts . these", "ggts . these are membrane", ". these are membrane bound", "are membrane bound heterodimeric", "membrane bound heterodimeric enzymes", "bound heterodimeric enzymes composed", "heterodimeric enzymes composed of light", "enzymes composed of light and", "composed of light and heavy", "of light and heavy peptide", "light and heavy peptide chains.", "and heavy peptide chains. extracellular", "heavy peptide chains. extracellular glutathione", "chains. extracellular glutathione gsh", "glutathione gsh or", "gsh or its conjugates", "or its conjugates can be", "its conjugates can be hydrolysed", "conjugates can be hydrolysed to", "can be hydrolysed to give", "be hydrolysed to give cysteinylglycine", "to give cysteinylglycine cg", "cysteinylglycine cg or", "cg or cg conjugates", "or cg conjugates and", "cg conjugates and free", "conjugates and free glutamate", 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autosomal recessive disorder characterised", "autosomal recessive disorder characterised by", "recessive disorder characterised by increased", "disorder characterised by increased gsh", "characterised by increased gsh concentration", "by increased gsh concentration in", "increased gsh concentration in the", "gsh concentration in the plasma", "concentration in the plasma and", "in the plasma and urine.", "the plasma and urine. mutations", "plasma and urine. mutations that", "and urine. mutations that cause", "urine. mutations that cause gluth", "mutations that cause gluth can", "that cause gluth can occur", "cause gluth can occur in", "gluth can occur in both", "can occur in both chains", "occur in both chains of", "in both chains of the", "both chains of the ggt1", "chains of the ggt1 dimer", "the ggt1 dimer heisterkamp", "ggt1 dimer heisterkamp et", "dimer heisterkamp et al.", "et al. 2008 aoyama", "al. 2008 aoyama &", "2008 aoyama & nakaki", "aoyama & nakaki 2013 ." ] }, { 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              the", "2006 .

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              the", "al. 2006 .

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"commonly uses the", "uses the cde system", "the cde system to", "cde system to depict", "system to depict the", "to depict the notation", "depict the notation of", "the notation of rh", "notation of rh genotypes", "rh genotypes race", "genotypes race 1948", "race 1948 . the", "1948 . the most", ". the most common", "the most common group", "most common group of", "common group of 3", "group of 3 genes", "of 3 genes inherited", "3 genes inherited is", "genes inherited is cde", "inherited is cde with", "is cde with ce", "with ce d", "ce d negative", "d negative being", "negative being the", "being the second most", "the second most common.", "second most common. rh", "most common. rh genotyping", "common. rh genotyping is", "rh genotyping is used", "genotyping is used in", "is used in blood", "used in blood transfusion", "blood transfusion paternity", "transfusion paternity testing", "paternity testing and to", "testing and to determine", "and to determine the", "to determine the risk", "determine the risk of", "the risk of hemolytic", "risk of hemolytic disease", "of hemolytic disease of", "disease of the newborn.", "rhesus rh blood", "rh blood group system", "blood group system including", "group system including the", "system including the rh", "the rh factor is", "rh factor is the", "factor is the second", "is the second most important", "the second most important blood", "second most important blood group", "most important blood group system", "important blood group system after", "blood group system after the", "group system after the abo", "system after the abo blood", "after the abo blood group", "the abo blood group system.", "abo blood group system. the", "blood group system. the rh", "group system. the rh blood", "system. the rh blood type", "the rh blood type was", "rh blood type was first", "blood type was first discovered", "type was first discovered in", "was first discovered in 1937", "first discovered in 1937 by", "discovered in 1937 by karl", "in 1937 by karl landsteiner", "1937 by karl landsteiner and", "by karl landsteiner and alexander", "karl landsteiner and alexander s.", "landsteiner and alexander s. wiener", "and alexander s. wiener who", "alexander s. wiener who named", "s. wiener who named it", "wiener who named it after", "who named it after the", "named it after the rhesus", "it after the rhesus macaque", "after the rhesus macaque whose", "the rhesus macaque whose rbcs", "rhesus macaque whose rbcs were", "macaque whose rbcs were used", "whose rbcs were used to", "rbcs were used to generate", "were used to generate the", "used to generate the rabbit", "to generate the rabbit immune", "generate the rabbit immune serum", "the rabbit immune serum that", "rabbit immune serum that first", "immune serum that first detected", "serum that first detected the", "that first detected the human", "first detected the human blood", "detected the human blood group", "the human blood group system.", "human blood group system. subsequent", "blood group system. subsequent studies", "group system. subsequent studies by", "system. subsequent studies by them", "subsequent studies by them and", "studies by them and philip", "by them and philip levine", "them and philip levine and", "and philip levine and rufus", "philip levine and rufus stetson", "levine and rufus stetson identified", "and rufus stetson identified the", "rufus stetson identified the antigen", "stetson identified the antigen that", "identified the antigen that induced", "the antigen that induced this", "antigen that induced this immunization", "that induced this immunization as", "induced this immunization as the", "this immunization as the \\rh", "immunization as the \\rh factor\\", "as the \\rh factor\\ and", "the \\rh factor\\ and also", "\\rh factor\\ and also its", "factor\\ and also its association", "and also its association with", "also its association with hemolytic", "its association with hemolytic disease", "association with hemolytic disease of", "with hemolytic disease of the", "hemolytic disease of the newborn", "of the newborn levine", "the newborn levine &", "newborn levine & stetson", "& stetson 1984 landsteiner", "stetson 1984 landsteiner &", "1984 landsteiner & wiener", "landsteiner & wiener 1941 .", "& wiener 1941 . of", "wiener 1941 . of the", "1941 . of the 50", ". of the 50 defined", "of the 50 defined rh", "the 50 defined rh blood", "50 defined rh blood group", "defined rh blood group antigens", "blood group antigens five", "antigens five d", "five d c/c", "d c/c and e/e", "c/c and e/e are", "and e/e are the", "e/e are the major", "are the major types expressed", "the major types expressed by", "major types expressed by the", "types expressed by the rhd", "expressed by the rhd and", "by the rhd and rhce", "the rhd and rhce genes", "rhd and rhce genes in", "and rhce genes in the", "rhce genes in the rh", "genes in the rh gene", "in the rh gene complex.", "the rh gene complex. rh", "rh gene complex. rh antigens", "gene complex. rh antigens are", "complex. rh antigens are expressed", "rh antigens are expressed on", "antigens are expressed on red", "are expressed on red cell", "on red cell rbc", "cell rbc membranes", "rbc membranes in association", "membranes in association with other", "in association with other membrane", "association with other membrane proteins", "with other membrane proteins and", "other membrane proteins and this", "membrane proteins and this whole", "proteins and this whole complex", "and this whole complex interacts", "this whole complex interacts with", "whole complex interacts with the", "complex interacts with the spectrin", "interacts with the spectrin based", "with the spectrin based skeleton", "the spectrin based skeleton and", "spectrin based skeleton and contributes", "based skeleton and contributes to", "skeleton and contributes to the", "and contributes to the maintenance", "contributes to the maintenance of", "to the maintenance of the", "the maintenance of the mechanical", "maintenance of the mechanical properties", "of the mechanical properties of", "the mechanical properties of the", "mechanical properties of the rbc", "properties of the rbc membrane", "the rbc membrane van", "rbc membrane van kim", "membrane van kim et", "van kim et al. 2006", "kim et al. 2006 .

              the", "et al. 2006 .

              the rhd", "al. 2006 .

              the rhd gene", "2006 .

              the rhd gene produces", ".

              the rhd gene produces the", "rhd gene produces the d", "gene produces the d antigen", "the d antigen the", "d antigen the most", "antigen the most immunogenic", "the most immunogenic rh antigen.", "most immunogenic rh antigen. the", "immunogenic rh antigen. the term", "rh antigen. the term \\rh", "antigen. the term \\rh factor\\", "the term \\rh factor\\ refers", "term \\rh factor\\ refers only", "\\rh factor\\ refers only to", "factor\\ refers only to the", "refers only to the d", "only to the d antigen", "the d antigen rh", "d antigen rh positive", "positive rh+ individuals", "rh+ individuals have the", "individuals have the d antigen", "have the d antigen on", "the d antigen on their", "d antigen on their rbc", "antigen on their rbc membranes", "on their rbc membranes whereas", "their rbc membranes whereas rh", "rbc membranes whereas rh negative", "whereas rh negative rh", "rh individuals don't.", "individuals don't. humans are not", "don't. humans are not born", "humans are not born with", "are not born with antibodies", "not born with antibodies towards", "born with antibodies towards the", "with antibodies towards the d", "antibodies towards the d antigen", "towards the d antigen in", "the d antigen in their", "d antigen in their blood", "in their blood they", "their blood they have", "blood they have to", "they have to be exposed", "have to be exposed to", "to be exposed to it", "exposed to it through", "to it through blood", "it through blood transfusion", "through blood transfusion or placental", "blood transfusion or placental exposure", "transfusion or placental exposure during", "or placental exposure during pregnancy", "exposure during pregnancy at", "during pregnancy at some", "pregnancy at some point", "at some point in their", "some point in their lives", "point in their lives before", "in their lives before antibodies", "their lives before antibodies are", "lives before antibodies are made", "before antibodies are made against", "antibodies are made against it.", "are made against it. once", "made against it. once exposed", "it. once exposed however", "exposed however rh+", "however rh+ individuals remain", "rh+ individuals remain sensitive for", "individuals remain sensitive for the", "remain sensitive for the rest", "sensitive for the rest of", "for the rest of their", "the rest of their lives.", "rest of their lives. importantly", "their lives. importantly if", "lives. importantly if individuals", "importantly if individuals are", "if individuals are rh+ and", "individuals are rh+ and are", "are rh+ and are exposed", "rh+ and are exposed to", "and are exposed to rh", "exposed to rh blood", "rh blood no", "blood no immune response", "no immune response is mounted.", "immune response is mounted. anti", "response is mounted. anti d", "is mounted. anti d antibodies", "mounted. anti d antibodies are", "anti d antibodies are only", "d antibodies are only seen", "antibodies are only seen if", "are only seen if an", "only seen if an individual", "seen if an individual is", "if an individual is lacking", "an individual is lacking the", "individual is lacking the d", "is lacking the d antigen", "rh and is", "and is exposed to rh+", "is exposed to rh+ blood.", "exposed to rh+ blood. the", "to rh+ blood. the rhce", "rh+ blood. the rhce gene", "blood. the rhce gene produces", "the rhce gene produces polypeptides", "rhce gene produces polypeptides with", "gene produces polypeptides with c/c", "produces polypeptides with c/c and", "polypeptides with c/c and e/e", "with c/c and e/e antigens.

              these", "c/c and e/e antigens.

              these polypeptides", "and e/e antigens.

              these polypeptides are", "e/e antigens.

              these polypeptides are the", "antigens.

              these polypeptides are the core", "polypeptides are the core components", "are the core components of", "the core components of their", "core components of their respective", "components of their respective antigens", "of their respective antigens but", "their respective antigens but by", "respective antigens but by themselves", "antigens but by themselves are", "but by themselves are devoid", "by themselves are devoid of", "themselves are devoid of the", "are devoid of the immunoreactivity", "devoid of the immunoreactivity which", "of the immunoreactivity which defines", "the immunoreactivity which defines the", "immunoreactivity which defines the rh", "which defines the rh antigens.", "defines the rh antigens. the", "the rh antigens. the remaining", "rh antigens. the remaining antigens", "antigens. the remaining antigens are", "the remaining antigens are produced", "remaining antigens are produced by", "antigens are produced by partial", "are produced by partial deletion", "by partial deletion recombination", "deletion recombination mutation", "recombination mutation or", "mutation or polymorphisms of", "or polymorphisms of one or", "polymorphisms of one or both", "of one or both rhd", "one or both rhd and", "or both rhd and rhce", "both rhd and rhce genes", "and rhce genes cartron", "rhce genes cartron 1999", "genes cartron 1999 .", "1999 . together these", ". together these antigens", "together these antigens form", "these antigens form the most", "antigens form the most complex", "form the most complex and", "the most complex and polymorphic", "most complex and polymorphic blood", "complex and polymorphic blood group", "and polymorphic blood group system", "polymorphic blood group system based", "blood group system based on", "group system based on the", "system based on the multitude", "based on the multitude of", "on the multitude of phenotypes", "the multitude of phenotypes that", "multitude of phenotypes that can", "of phenotypes that can be", "phenotypes that can be expressed", "that can be expressed on", "can be expressed on the", "be expressed on the rbc", "expressed on the rbc surface.", "on the rbc surface. the", "the rbc surface. the fisher", "rbc surface. the fisher race", "surface. the fisher race system", "fisher race system the", "race system the nomenclature", "system the nomenclature used", "the nomenclature used most commonly", "used most commonly uses", "most commonly uses the", "commonly uses the cde", "uses the cde system to", "the cde system to depict", "cde system to depict the", "system to depict the notation", "to depict the notation of", "depict the notation of rh", "the notation of rh genotypes", "of rh genotypes race", "rh genotypes race 1948", "genotypes race 1948 .", "race 1948 . the most", "1948 . the most common", ". the most common group", "the most common group of", "most common group of 3", "common group of 3 genes", "group of 3 genes inherited", "of 3 genes inherited is", "3 genes inherited is cde", "genes inherited is cde with", "inherited is cde with ce", "cde with ce d", "with ce d negative", "d negative being the", "negative being the second", "being the second most common.", "the second most common. rh", "second most common. rh genotyping", "most common. rh genotyping is", "common. rh genotyping is used", "rh genotyping is used in", "genotyping is used in blood", "is used in blood transfusion", "in blood transfusion paternity", "blood transfusion paternity testing", "transfusion paternity testing and", "paternity testing and to determine", "testing and to determine the", "and to determine the risk", "to determine the risk of", "determine the risk of hemolytic", "the risk of hemolytic disease", "risk of hemolytic disease of", "of hemolytic disease of the", "hemolytic disease of the newborn." ] }, { "record_id": "GLY_000594_1_1551", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9603381", "r hsa", "hsa 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              the", "of high mannose xenoglycans.
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              the first n glycan modification", "first n glycan modification step", "n glycan modification step is", "glycan modification step is the", "modification step is the trimming", "step is the trimming of", "is the trimming of up", "the trimming of up to", "trimming of up to four", "of up to four mannoses", "up to four mannoses by", "to four mannoses by one", "four mannoses by one of", "mannoses by one of three", "by one of three mannosidase", "one of three mannosidase enzymes.", "of three mannosidase enzymes. moreover", "mannosidase enzymes. moreover glycoproteins", "enzymes. moreover glycoproteins that", "moreover glycoproteins that have", "glycoproteins that have not entered", "that have not entered in", "have not entered in the", "not entered in the calnexin/calreticulin", "entered in the calnexin/calreticulin cycle", "in the calnexin/calreticulin cycle or", "the calnexin/calreticulin cycle or that", "calnexin/calreticulin cycle or that have", "cycle or that have not", "or that have not had", "that have not had their", "have not had their glucose", "not had their glucose residues", "had their glucose residues trimmed", "their glucose residues trimmed earlier", "glucose residues trimmed earlier in", "residues trimmed earlier in the", "trimmed earlier in the er", "in the er can", "the er can enter", "er can enter the", "can enter the main pathway", "enter the main pathway here", "the main pathway here due", "main pathway here due to", "pathway here due to the", "here due to the existence", "due to the existence to", "to the existence to an", "the existence to an alternative", "existence to an alternative route", "to an alternative route catalyzed", "an alternative route catalyzed by", "alternative route catalyzed by the", "route catalyzed by the enzyme", "catalyzed by the enzyme endomannosidase", "by the enzyme endomannosidase i", "enzyme endomannosidase i schachter", "i schachter 2000", "schachter 2000 stanley", "2000 stanley et al", "stanley et al 2009", "et al 2009
              " ] }, { "record_id": "GLY_000594_1_1559", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975110", "r hsa", "hsa 975110", "r hsa 975110" ] }, { "record_id": "GLY_000594_1_1559", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "traf6 mediated", "mediated irf7", "irf7 activation", "activation in", "in tlr7/8", "tlr7/8 or", "or 9", "9 signaling", "traf6 mediated irf7", "mediated irf7 activation", "irf7 activation in", "activation in tlr7/8", "in tlr7/8 or", "tlr7/8 or 9", "or 9 signaling", "traf6 mediated irf7 activation", "mediated irf7 activation in", "irf7 activation in tlr7/8", "activation in tlr7/8 or", "in tlr7/8 or 9", "tlr7/8 or 9 signaling", "traf6 mediated irf7 activation in", "mediated irf7 activation in tlr7/8", "irf7 activation in tlr7/8 or", "activation in tlr7/8 or 9", "in tlr7/8 or 9 signaling", "in plasmacytoid", "plasmacytoid dendritic", "dendritic cell", "cell induction", "induction of", "of type", "type i", "i ifns", "ifns critically", "critically depends", "depends on", "on ifn", "ifn regulatory", "regulatory factor", "factor 7", "7 in", "in tlr7", "tlr7 and", "and 9", "honda et", "et al", "al 2005", "2005 .", ". irf", "irf 7", "but not", "not irf3", "interacts with", "with myd88", "and iraks", "iraks and", "and translocates", "translocates to", "to the", "the nucleus", "nucleus upon", "upon phosphorylation", "kawai et", "al 2004", "uematsu et", "2005 .

              ", ".

              tlr7/8", "tlr7/8 signaling", "signaling was", "was shown", "shown to", "to induce", "induce irf5", "irf5 activation", "activation along", "along with", "with irf7", "schoenemeyer et", "while irf8", "tsujimura h", "h et", "and irf1", "irf1 were", "were reported", "reported to", "to be", "be implicated", "implicated in", "in tlr9", "tlr9 signaling.", "in plasmacytoid dendritic", "plasmacytoid dendritic cell", "dendritic cell induction", "cell induction of", "induction of type", "of type i", "type i ifns", "i ifns critically", "ifns critically depends", "critically depends on", "depends on ifn", "on ifn regulatory", "ifn regulatory factor", "regulatory factor 7", "factor 7 in", "7 in tlr7", "in tlr7 and", "tlr7 and 9", "and 9 signaling", "signaling honda", "honda et al", "et al 2005", "al 2005 .", "2005 . irf", ". irf 7", "7 but", "but not irf3", "irf3 interacts", "interacts with myd88", "myd88 traf6", "traf6 and", "and iraks and", "iraks and translocates", "and translocates to", "translocates to the", "to the nucleus", "the nucleus upon", "nucleus upon phosphorylation", "phosphorylation kawai", "kawai et al", "et al 2004", "2004 uematsu", "uematsu et al", "al 2005 .

              ", "2005 .

              tlr7/8", ".

              tlr7/8 signaling", "tlr7/8 signaling was", "signaling was shown", "was shown to", "shown to induce", "to induce irf5", "induce irf5 activation", "irf5 activation along", "activation along with", "along with irf7", "irf7 schoenemeyer", "schoenemeyer et al", "irf8 tsujimura", "tsujimura h et", "h et al", "2004 and", "and irf1 were", "irf1 were reported", "were reported to", "reported to be", "to be implicated", "be implicated in", "implicated in tlr9", "in tlr9 signaling.", "in plasmacytoid dendritic cell", "plasmacytoid dendritic cell induction", "dendritic cell induction of", "cell induction of type", "induction of type i", "of type i ifns", "type i ifns critically", "i ifns critically depends", "ifns critically depends on", "critically depends on ifn", "depends on ifn regulatory", "on ifn regulatory factor", "ifn regulatory factor 7", "regulatory factor 7 in", "factor 7 in tlr7", "7 in tlr7 and", "in tlr7 and 9", "tlr7 and 9 signaling", "9 signaling honda", "signaling honda et", "honda et al 2005", "et al 2005 .", "al 2005 . irf", "2005 . irf 7", "irf 7 but", "7 but not", "not irf3 interacts", "irf3 interacts with", "with myd88 traf6", "traf6 and iraks", "and iraks and translocates", "iraks and translocates to", "and translocates to the", "translocates to the nucleus", "to the nucleus upon", "the nucleus upon phosphorylation", "upon phosphorylation kawai", "phosphorylation kawai et", "kawai et al 2004", "al 2004 uematsu", "2004 uematsu et", "uematsu et al 2005", "et al 2005 .

              ", "al 2005 .

              tlr7/8", "2005 .

              tlr7/8 signaling", ".

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              ", "et al 2005 .

              tlr7/8", "al 2005 .

              tlr7/8 signaling", "2005 .

              tlr7/8 signaling was", ".

              tlr7/8 signaling was shown", "tlr7/8 signaling was shown to", "signaling was shown to induce", "was shown to induce irf5", "shown to induce irf5 activation", "to induce irf5 activation along", "induce irf5 activation along with", "irf5 activation along with irf7", "along with irf7 schoenemeyer", "with irf7 schoenemeyer et", "irf7 schoenemeyer et al", "al 2005 while", "2005 while irf8", "while irf8 tsujimura h", "irf8 tsujimura h et", "tsujimura h et al 2004", "et al 2004 and", "al 2004 and irf1", "2004 and irf1 were", "and irf1 were reported to", "irf1 were reported to be", "were reported to be implicated", "reported to be implicated in", "to be implicated in tlr9", "be implicated in tlr9 signaling." ] }, { "record_id": "GLY_000594_1_1560", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "975956", "r hsa", "hsa 975956", "r hsa 975956" ] }, { "record_id": "GLY_000594_1_1560", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nonsense mediated", "mediated decay", "independent of", "of the", "the exon", "exon junction", "junction complex", "nonsense mediated decay", "decay nmd", "nmd independent", "independent of the", "of the exon", "the exon junction", "exon junction complex", "complex ejc", "mediated decay nmd", "nmd independent of", "independent of the exon", "of the exon junction", "the exon junction complex", "junction complex ejc", "nonsense mediated decay nmd", "decay nmd independent", "nmd independent of the", "independent of the exon junction", "of the exon junction complex", "exon junction complex ejc", "decay has", "has been", "been observed", "observed with", "with mrnas", "mrnas that", "that do", "do not", "not have", "have an", "an exon", "downstream of", "the termination", "termination codon", "reviewed in", "in isken", "isken and", "and maquat", "maquat 2007", "chang et", "et al.", "al. 2007", "behm ansmant", "ansmant et", "rebbapragada and", "and lykke", "lykke andersen", "andersen 2009", "nicholson et", "al. 2010", "2010 .", ". in", "in these", "these cases", "cases the", "the trigger", "trigger is", "is unknown", "unknown but", "but a", "a correlation", "correlation with", "with the", "the length", "length of", "the 3'", "3' utr", "utr has", "has sometimes", "sometimes been", "been seen.", "seen. the", "the current", "current model", "model posits", "posits a", "a competition", "competition between", "between pabp", "pabp and", "and upf1", "upf1 for", "for access", "access to", "to erf3", "erf3 at", "at the", "the terminating", "terminating ribosome", "ivanov et", "al. 2008", "singh et", "in bhuvanagiri", "bhuvanagiri et", ". abnormally", "abnormally long", "long 3'", "3' utrs", "utrs may", "may prevent", "prevent pabp", "pabp from", "from efficiently", "efficiently interacting", "interacting with", "with erf3", "erf3 and", "and allow", "allow upf1", "upf1 to", "to bind", "bind erf3", "erf3 instead.", "instead. long", "long utrs", "utrs with", "with hairpin", "hairpin loops", "loops may", "may bring", "bring pabp", "pabp closer", "closer to", "and help", "help evade", "evade nmd", "eberle et", "2008 .
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              the pathway", "2008 .
              the pathway of", ".
              the pathway of degradation", "pathway of degradation taken", "of degradation taken during", "degradation taken during ejc", "taken during ejc independent", "during ejc independent nmd", "ejc independent nmd has", "independent nmd has not", "nmd has not been", "has not been elucidated.", "not been elucidated. it", "been elucidated. it is", "elucidated. it is thought", "it is thought that", "is thought that phosphorylation", "thought that phosphorylation of", "that phosphorylation of upf1", "phosphorylation of upf1 by", "of upf1 by smg1", "upf1 by smg1 and", "by smg1 and recruitment", "smg1 and recruitment of", "and recruitment of smg6", "recruitment of smg6 or", "of smg6 or smg5", "smg6 or smg5 and", "or smg5 and smg7", "smg5 and smg7 are", "and smg7 are involved", "are involved as", "involved as with", "as with ejc enhanced", "with ejc enhanced nmd", "enhanced nmd but", "nmd but this", "but this has not", "this has not yet", "has not yet been", "not yet been shown.", "nonsense mediated decay has been", "mediated decay has been observed", "decay has been observed with", "has been observed with mrnas", "been observed with mrnas that", "observed with mrnas that do", "with mrnas that do not", "mrnas that do not have", "that do not have an", "do not have an exon", "not have an exon junction", "have an exon junction complex", "complex ejc downstream", "ejc downstream of the", "downstream of the termination codon", "the termination codon reviewed", "termination codon reviewed in", "codon reviewed in isken", "reviewed in isken and maquat", "in isken and maquat 2007", "and maquat 2007 chang", "maquat 2007 chang et", "2007 chang et al.", "et al. 2007 behm", "al. 2007 behm ansmant", "2007 behm ansmant et", "behm ansmant et al. 2007", "et al. 2007 rebbapragada", "al. 2007 rebbapragada and", "2007 rebbapragada and lykke", "rebbapragada and lykke andersen 2009", "lykke andersen 2009 nicholson", "andersen 2009 nicholson et", "2009 nicholson et al.", "nicholson et al. 2010 .", "et al. 2010 . in", "al. 2010 . in these", "2010 . in these cases", ". in these cases the", "in these cases the trigger", "these cases the trigger is", "cases the trigger is unknown", "the trigger is unknown but", "trigger is unknown but a", "is unknown but a correlation", "unknown but a correlation with", "but a correlation with the", "a correlation with the length", "correlation with the length of", "with the length of the", "the length of the 3'", "length of the 3' utr", "of the 3' utr has", "the 3' utr has sometimes", "3' utr has sometimes been", "utr has sometimes been seen.", "has sometimes been seen. the", "sometimes been seen. the current", "been seen. the current model", "seen. the current model posits", "the current model posits a", "current model posits a competition", "model posits a competition between", "posits a competition between pabp", "a competition between pabp and", "competition between pabp and upf1", "between pabp and upf1 for", "pabp and upf1 for access", "and upf1 for access to", "upf1 for access to erf3", "for access to erf3 at", "access to erf3 at the", "to erf3 at the terminating", "erf3 at the terminating ribosome", "the terminating ribosome ivanov", "terminating ribosome ivanov et", "ribosome ivanov et al.", "et al. 2008 singh", "al. 2008 singh et", "2008 singh et al.", "et al. 2008 reviewed", "al. 2008 reviewed in", "2008 reviewed in bhuvanagiri", "reviewed in bhuvanagiri et al.", "in bhuvanagiri et al. 2010", "bhuvanagiri et al. 2010 .", "et al. 2010 . abnormally", "al. 2010 . abnormally long", "2010 . abnormally long 3'", ". abnormally long 3' utrs", "abnormally long 3' utrs may", "long 3' utrs may prevent", "3' utrs may prevent pabp", "utrs may prevent pabp from", "may prevent pabp from efficiently", "prevent pabp from efficiently interacting", "pabp from efficiently interacting with", "from efficiently interacting with erf3", "efficiently interacting with erf3 and", "interacting with erf3 and allow", "with erf3 and allow upf1", "erf3 and allow upf1 to", "and allow upf1 to bind", "allow upf1 to bind erf3", "upf1 to bind erf3 instead.", "to bind erf3 instead. long", "bind erf3 instead. long utrs", "erf3 instead. long utrs with", "instead. long utrs with hairpin", "long utrs with hairpin loops", "utrs with hairpin loops may", "with hairpin loops may bring", "hairpin loops may bring pabp", "loops may bring pabp closer", "may bring pabp closer to", "bring pabp closer to erf3", "pabp closer to erf3 and", "closer to erf3 and help", "to erf3 and help evade", "erf3 and help evade nmd", "help evade nmd eberle", "evade nmd eberle et", "nmd eberle et al.", "eberle et al. 2008 .
              the", "et al. 2008 .
              the pathway", "al. 2008 .
              the pathway of", "2008 .
              the pathway of degradation", ".
              the pathway of degradation taken", "pathway of degradation taken during", "of degradation taken during ejc", "degradation taken during ejc independent", "taken during ejc independent nmd", "during ejc independent nmd has", "ejc independent nmd has not", "independent nmd has not been", "nmd has not been elucidated.", "has not been elucidated. it", "not been elucidated. it is", "been elucidated. it is thought", "elucidated. it is thought that", "it is thought that phosphorylation", "is thought that phosphorylation of", "thought that phosphorylation of upf1", "that phosphorylation of upf1 by", "phosphorylation of upf1 by smg1", "of upf1 by smg1 and", "upf1 by smg1 and recruitment", "by smg1 and recruitment of", "smg1 and recruitment of smg6", "and recruitment of smg6 or", "recruitment of smg6 or smg5", "of smg6 or smg5 and", "smg6 or smg5 and smg7", "or smg5 and smg7 are", "smg5 and smg7 are involved", "smg7 are involved as", "are involved as with", "involved as with ejc", "as with ejc enhanced nmd", "ejc enhanced nmd but", "enhanced nmd but this", "nmd but this has", "but this has not yet", "this has not yet been", "has not yet been shown." ] }, { "record_id": "GLY_000594_1_1561", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "977068", "r hsa", "hsa 977068", "r hsa 977068" ] }, { "record_id": "GLY_000594_1_1561", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "termination of", "of o", "o glycan", "glycan biosynthesis", "termination of o", "of o glycan", "o glycan biosynthesis", "termination of o glycan", "of o glycan biosynthesis", "termination of o glycan biosynthesis", "biosynthesis can", "can be", "be terminated", "or modified", "by the", "the addition", "addition of", "of sialic", "sialic acid", "acid residues", "residues on", "on core", "core 1", "1 and", "and 2", "2 glycoproteins", "glycoproteins by", "by sialyltransferases", "varki et", "et al.", "al. 2009", "2009 .", "glycan biosynthesis can", "biosynthesis can be", "can be terminated", "terminated or", "modified by", "by the addition", "the addition of", "addition of sialic", "of sialic acid", "sialic acid residues", "acid residues on", "residues on core", "on core 1", "core 1 and", "1 and 2", "and 2 glycoproteins", "2 glycoproteins by", "glycoproteins by sialyltransferases", "sialyltransferases varki", "varki et al.", "et al. 2009", "al. 2009 .", "o glycan biosynthesis can", "glycan biosynthesis can be", "biosynthesis can be terminated", "be terminated or", "terminated or modified", "or modified by", "modified by the", "by the addition of", "the addition of sialic", "addition of sialic acid", "of sialic acid residues", "sialic acid residues on", "acid residues on core", "residues on core 1", "on core 1 and", "core 1 and 2", "1 and 2 glycoproteins", "and 2 glycoproteins by", "2 glycoproteins by sialyltransferases", "by sialyltransferases varki", "sialyltransferases varki et", "varki et al. 2009", "et al. 2009 .", "o glycan biosynthesis can be", "glycan biosynthesis can be terminated", "can be terminated or", "be terminated or modified", "or modified by the", "modified by the addition", "by the addition of sialic", "the addition of sialic acid", "addition of sialic acid residues", "of sialic acid residues on", "sialic acid residues on core", "acid residues on core 1", "residues on core 1 and", "on core 1 and 2", "core 1 and 2 glycoproteins", "1 and 2 glycoproteins by", "and 2 glycoproteins by sialyltransferases", "glycoproteins by sialyltransferases varki", "by sialyltransferases varki et", "sialyltransferases varki et al.", "varki et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1562", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111452", "r hsa", "hsa 111452", "r hsa 111452" ] }, { "record_id": "GLY_000594_1_1562", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ 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this may induce", "bak. this may induce its", "this may induce its intramembranous", "may induce its intramembranous oligomerization", "induce its intramembranous oligomerization into", "its intramembranous oligomerization into a", "intramembranous oligomerization into a pore", "oligomerization into a pore for", "into a pore for cytochrome", "a pore for cytochrome c", "pore for cytochrome c efflux." ] }, { "record_id": "GLY_000594_1_1563", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111457", "r hsa", "hsa 111457", "r hsa 111457" ] }, { "record_id": "GLY_000594_1_1563", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "release of", "of apoptotic", "apoptotic factors", "factors from", "from the", "the mitochondria", "release of apoptotic", "of apoptotic factors", "apoptotic factors from", "factors from the", "from the mitochondria", "release of apoptotic factors", "of apoptotic factors from", 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"the active caspase\u20119 holoenzyme", "active caspase\u20119 holoenzyme activates", "caspase\u20119 holoenzyme activates downstream", "holoenzyme activates downstream effector", "activates downstream effector caspases\u20113", "downstream effector caspases\u20113 and", "effector caspases\u20113 and \u20117.", "caspases\u20113 and \u20117. the", "and \u20117. the activated", "\u20117. the activated effector", "the activated effector caspases", "activated effector caspases then", "effector caspases then cleave", "caspases then cleave various", "then cleave various cellular", "cleave various cellular proteins.", "upon its release from the", "its release from the mitochondrial", "release from the mitochondrial intermembrane", "from the mitochondrial intermembrane space", "mitochondrial intermembrane space cytochrome", "intermembrane space cytochrome c", "c cysc binds", "cysc binds to and", "binds to and causes an", "to and causes an atp", "and causes an atp mediated", "causes an atp 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oligomeric protein complex", "activating oligomeric protein complex named", "oligomeric protein complex named apoptosome.", "protein complex named apoptosome. the", "complex named apoptosome. the active", "named apoptosome. the active caspase\u20119", "apoptosome. the active caspase\u20119 holoenzyme", "the active caspase\u20119 holoenzyme activates", "active caspase\u20119 holoenzyme activates downstream", "caspase\u20119 holoenzyme activates downstream effector", "holoenzyme activates downstream effector caspases\u20113", "activates downstream effector caspases\u20113 and", "downstream effector caspases\u20113 and \u20117.", "effector caspases\u20113 and \u20117. the", "caspases\u20113 and \u20117. the activated", "and \u20117. the activated effector", "\u20117. the activated effector caspases", "the activated effector caspases then", "activated effector caspases then cleave", "effector caspases then cleave various", "caspases then cleave various cellular", "then cleave various cellular proteins." ] }, { "record_id": "GLY_000594_1_1565", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111469", "r hsa", "hsa 111469", "r hsa 111469" ] }, { "record_id": "GLY_000594_1_1565", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "xiap regulated", "regulated apoptotic", "apoptotic response", "smac xiap", "xiap regulated apoptotic", "regulated apoptotic response", "smac xiap regulated", "xiap regulated apoptotic response", "smac xiap regulated apoptotic", "once released", "released from", "from the", "the mitochondria", "smac binds", "binds to", "to iap", "iap family", "family proteins", "proteins displacing", "displacing them", "them from", "from caspase:iap", "caspase:iap complexes", "complexes liberating", "liberating the", "the active", "active caspases.", "once released from", "released from the", "from the mitochondria", "mitochondria smac", "smac binds to", "binds to iap", 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"activation and caspase independent cytotoxicity", "caspase independent cytotoxicity saelens", "independent cytotoxicity saelens et", "cytotoxicity saelens et al.", "saelens et al. 2004", "et al. 2004 ." ] }, { "record_id": "GLY_000594_1_1567", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "111995", "r hsa", "hsa 111995", "r hsa 111995" ] }, { "record_id": "GLY_000594_1_1567", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "phospho pla2", "pla2 pathway", "phospho pla2 pathway", "phospholipase a2", "enzymes hydrolyze", "hydrolyze arachidonic", "arachidonic acid", "from the", "the sn", "sn 2", "2 position", "position of", "of phospholipids.", "phospholipids. aa", "aa is", "is a", "a precursor", "precursor of", "of eicosanoids", "lipid mediators", "mediators involved", "involved in", "in inflammtory", "inflammtory responses.", "responses. pla2", "pla2 enzymes", "enzymes function", "function as", 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and alkbh3", "alkbh2 and alkbh3 can also", "and alkbh3 can also repair", "alkbh3 can also repair 1", "can also repair 1 ethyladenine", "repair 1 ethyladenine 1", "1 ethyladenine 1 eta", "1 eta residues in", "eta residues in dna", "residues in dna with the", "in dna with the release", "dna with the release of", "with the release of acetaldehyde", "release of acetaldehyde duncan", "of acetaldehyde duncan et", "acetaldehyde duncan et al.", "duncan et al. 2002", "al. 2002 lee", "2002 lee et al.", "lee et al. 2005 ." ] }, { "record_id": "GLY_000594_1_1569", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "112126", "r hsa", "hsa 112126", "r hsa 112126" ] }, { "record_id": "GLY_000594_1_1569", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "alkbh3 mediated", "mediated reversal", "reversal of", "of alkylation", "alkylation damage", "alkbh3 mediated reversal", "mediated reversal of", "reversal of 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              hydroxylated", "2011 .
              hydroxylated asparagine", ".
              hydroxylated asparagine interferes", "asparagine interferes with", "interferes with the", "with the ability", "the ability of", "ability of hif", "of hif alpha", "hif alpha to", "alpha to interact", "to interact with", "interact with p300", "with p300 and", "p300 and cbp", "and cbp while", "cbp while hydroxylated", "while hydroxylated proline", "hydroxylated proline facilitates", "proline facilitates the", "facilitates the interaction", "the interaction of", "interaction of hif", "hif alpha with", "alpha with the", "with the e3", "the e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase vhl", "vhl causing", "causing ubiquitination and", "ubiquitination and proteolysis", "and proteolysis of", "proteolysis of hif", "of hif alpha.", "hif alpha. hypoxia", "alpha. hypoxia inhibits", "hypoxia inhibits both", "inhibits both types", "types of hydroxylation", "hydroxylation resulting", "resulting in the", "in the stabilization", "the stabilization of", "stabilization of hif", "alpha which", "which then enters", "then enters the", "enters the nucleus", "nucleus binds", "binds hif beta", "beta and", "and recruits p300", "recruits p300 and", "and cbp to", "cbp to activate", "to activate target", "activate target genes", "target genes such", "genes such as", "such as epo", "as epo and", "epo and vegf.", "oxygen plays a central", "plays a central role", "a central role in", "central role in the", "role in the functioning", "in the functioning of", "the functioning of human", "functioning of human cells:", "of human cells: it", "human cells: it is", "cells: it is both", "it is both essential", "is both essential for", "both essential for normal", "essential for normal metabolism", "for normal metabolism and", "normal metabolism and toxic.", "metabolism and toxic. here", "and toxic. here we", "toxic. here we have", "here we have annotated", "we have annotated one", "have annotated one aspect", "annotated one aspect of", "one aspect of cellular", "aspect of cellular responses", "of cellular responses to", "cellular responses to oxygen", "to oxygen the", "oxygen the role", "the role of hypoxia", "role of hypoxia inducible", "of hypoxia inducible factor", "hypoxia inducible factor in", "inducible factor in regulating", "factor in regulating cellular", "in regulating cellular transcriptional", "regulating cellular transcriptional responses", "cellular transcriptional responses to", "transcriptional responses to changes", "responses to changes in", "to changes in oxygen", "changes in oxygen availability.

              in", "in oxygen availability.

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              hydroxylated", "al. 2011 .
              hydroxylated asparagine", "2011 .
              hydroxylated asparagine interferes", ".
              hydroxylated asparagine interferes with", "asparagine interferes with the", "interferes with the ability", "with the ability of", "the ability of hif", "ability of hif alpha", "of hif alpha to", "hif alpha to interact", "alpha to interact with", "to interact with p300", "interact with p300 and", "with p300 and cbp", "p300 and cbp while", "and cbp while hydroxylated", "cbp while hydroxylated proline", "while hydroxylated proline facilitates", "hydroxylated proline facilitates the", "proline facilitates the interaction", "facilitates the interaction of", "the interaction of hif", "interaction of hif alpha", "of hif alpha with", "hif alpha with the", "alpha with the e3", "with the e3 ubiquitin", "the e3 ubiquitin ligase", "e3 ubiquitin ligase vhl", "ligase vhl causing", "vhl causing ubiquitination", "causing ubiquitination and proteolysis", "ubiquitination and proteolysis of", "and proteolysis of hif", "proteolysis of hif alpha.", "of hif alpha. hypoxia", "hif alpha. hypoxia inhibits", "alpha. hypoxia inhibits both", "hypoxia inhibits both types", "inhibits both types of", "both types of hydroxylation", "of hydroxylation resulting", "hydroxylation resulting in", "resulting in the stabilization", "in the stabilization of", "the stabilization of hif", "stabilization of hif alpha", "hif alpha which", "alpha which then", "which then enters the", "then enters the nucleus", "the nucleus binds", "nucleus binds hif", "hif beta and", "beta and recruits", "and recruits p300 and", "recruits p300 and cbp", "p300 and cbp to", "and cbp to activate", "cbp to activate target", "to activate target genes", "activate target genes such", "target genes such as", "genes such as epo", "such as epo and", "as epo and vegf.", "oxygen plays a central role", "plays a central role in", "a central role in the", "central role in the functioning", "role in the functioning of", "in the functioning of human", "the functioning of human cells:", "functioning of human cells: it", "of human cells: it is", "human cells: it is both", "cells: it is both essential", "it is both essential for", "is both essential for normal", "both essential for normal metabolism", "essential for normal metabolism and", "for normal metabolism and toxic.", "normal metabolism and toxic. here", "metabolism and toxic. here we", "and toxic. here we have", "toxic. here we have annotated", "here we have annotated one", "we have annotated one aspect", "have annotated one aspect of", "annotated one aspect of cellular", "one aspect of cellular responses", "aspect of cellular responses to", "of cellular responses to oxygen", "responses to oxygen the", "to oxygen the role", "oxygen the role of", "the role of hypoxia inducible", "role of hypoxia inducible factor", "of hypoxia inducible factor in", "hypoxia inducible factor in regulating", "inducible factor in regulating cellular", "factor in regulating cellular transcriptional", "in regulating cellular transcriptional responses", "regulating cellular transcriptional responses to", "cellular transcriptional responses to changes", "transcriptional responses to changes in", "responses to changes in oxygen", "to changes in oxygen availability.

              in", "changes in oxygen availability.

              in the", "in oxygen availability.

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              in the presence of", "availability.

              in the presence of oxygen", "the presence of oxygen members", "presence of oxygen members of", "of oxygen members of the", "oxygen members of the transcription", "members of the transcription factor", "of the transcription factor family", "the transcription factor family hif", "transcription factor family hif alpha", "family hif alpha comprising", "hif alpha comprising hif1a", "hif1a hif2a epas1", "epas1 and hif3a", "and hif3a are hydroxylated", "hif3a are hydroxylated on", "are hydroxylated on proline residues", "hydroxylated on proline residues by", "on proline residues by phd1", "residues by phd1 egln2", "egln1 and phd3", "phd3 egln3 and", "egln3 and on asparagine", "and on asparagine residues by", "on asparagine residues by hif1an", "residues by hif1an fih", "fih reviewed in", "reviewed in pouyssegur et al.", "in pouyssegur et al. 2006", "et al. 2006 semenza", "al. 2006 semenza 2007", "semenza 2007 kaelin and", "2007 kaelin and ratcliffe", "and ratcliffe 2008 nizet", "ratcliffe 2008 nizet and", "2008 nizet and johnson", "and johnson 2009 brahimi", "johnson 2009 brahimi horn", "2009 brahimi horn and", "brahimi horn and pouyssegur 2009", "and pouyssegur 2009 majmundar", "pouyssegur 2009 majmundar et", "2009 majmundar et al.", "et al. 2010 loenarz", "al. 2010 loenarz and", "2010 loenarz and schofield", "loenarz and schofield 2011 .", "and schofield 2011 . both", "schofield 2011 . both types", "2011 . both types of", ". both types of reaction", "both types of reaction require", "types of reaction require molecular", "of reaction require molecular oxygen", "reaction require molecular oxygen as", "require molecular oxygen as a", "molecular oxygen as a substrate", "oxygen as a substrate and", "as a substrate and it", "a substrate and it is", "substrate and it is probable", "and it is probable that", "it is probable that at", "is probable that at least", "probable that at least some", "that at least some hif", "at least some hif alpha", "least some hif alpha molecules", "some hif alpha molecules carry", "hif alpha molecules carry both", "alpha molecules carry both hydroxylated", "molecules carry both hydroxylated asparagine", "carry both hydroxylated asparagine and", "both hydroxylated asparagine and hydroxylated", "hydroxylated asparagine and hydroxylated proline", "and hydroxylated proline tian", "hydroxylated proline tian et", "proline tian et al.", "tian et al. 2011 .
              hydroxylated", "et al. 2011 .
              hydroxylated asparagine", "al. 2011 .
              hydroxylated asparagine interferes", "2011 .
              hydroxylated asparagine interferes with", ".
              hydroxylated asparagine interferes with the", "asparagine interferes with the ability", "interferes with the ability of", "with the ability of hif", "the ability of hif alpha", "ability of hif alpha to", "of hif alpha to interact", "hif alpha to interact with", "alpha to interact with p300", "to interact with p300 and", "interact with p300 and cbp", "with p300 and cbp while", "p300 and cbp while hydroxylated", "and cbp while hydroxylated proline", "cbp while hydroxylated proline facilitates", "while hydroxylated proline facilitates the", "hydroxylated proline facilitates the interaction", "proline facilitates the interaction of", "facilitates the interaction of hif", "the interaction of hif alpha", "interaction of hif alpha with", "of hif alpha with the", "hif alpha with the e3", "alpha with the e3 ubiquitin", "with the e3 ubiquitin ligase", "the e3 ubiquitin ligase vhl", "ubiquitin ligase vhl causing", "ligase vhl causing ubiquitination", "vhl causing ubiquitination and", "causing ubiquitination and proteolysis of", "ubiquitination and proteolysis of hif", "and proteolysis of hif alpha.", "proteolysis of hif alpha. hypoxia", "of hif alpha. hypoxia inhibits", "hif alpha. hypoxia inhibits both", "alpha. hypoxia inhibits both types", "hypoxia inhibits both types of", "inhibits both types of hydroxylation", "types of hydroxylation resulting", "of hydroxylation resulting in", "hydroxylation resulting in the", "resulting in the stabilization of", "in the stabilization of hif", "the stabilization of hif alpha", "of hif alpha which", "hif alpha which then", "alpha which then enters", "which then enters the nucleus", "enters the nucleus binds", "the nucleus binds hif", "nucleus binds hif beta", "binds hif beta and", "hif beta and recruits", "beta and recruits p300", "and recruits p300 and cbp", "recruits p300 and cbp to", "p300 and cbp to activate", "and cbp to activate target", "cbp to activate target genes", "to activate target genes such", "activate target genes such as", "target genes such as epo", "genes such as epo and", "such as epo and vegf." ] }, { "record_id": "GLY_000594_1_1574", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1296053", "r hsa", "hsa 1296053", "r hsa 1296053" ] }, { "record_id": "GLY_000594_1_1574", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "classical kir", "kir channels", "classical kir channels", "channels are", "are inwardly", "inwardly rectifying", "rectifying k+", "k+ channels", "channels with", "with strong", "strong inwardly", "rectifying currents", "currents that", "that contribute", "contribute to", "to highly", "highly negative", "negative resting", "resting membrane", "membrane potential", "prolonged action", "action potential", "potential plateau", "plateau and", "and rapid", "rapid repolarization", "repolarization in", "in the", "the final", "final stage", "stage of", "of action", "action 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heterotetramers.", "5.1 work as heterotetramers. these", "work as heterotetramers. these channels", "as heterotetramers. these channels transport", "heterotetramers. these channels transport k+", "these channels transport k+ from", "channels transport k+ from cytosol", "transport k+ from cytosol to", "k+ from cytosol to the", "from cytosol to the lumen", "cytosol to the lumen of", "to the lumen of the", "the lumen of the tubules." ] }, { "record_id": "GLY_000594_1_1576", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "1299287", "r hsa", "hsa 1299287", "r hsa 1299287" ] }, { "record_id": "GLY_000594_1_1576", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "tandem pore", "pore domain", "domain halothane", "halothane inhibited", "inhibited k+", "k+ channel", "tandem pore domain", "pore domain halothane", "domain halothane inhibited", "halothane inhibited k+", "inhibited k+ channel", "channel thik", 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              ", "z dna binding", "dna binding protein", "binding protein 1", "1 zbp1", "also known as", "as dna", "dna dependent activator", "dependent activator of", "activator of ifn", "of ifn regulatory", "ifn regulatory factors", "factors dai", "dai was", "was reported to", "reported to initiate", "to initiate innate", "initiate innate immune", "innate immune responses", "immune responses in", "responses in murine", "in murine l929", "murine l929 cells", "l929 cells upon", "cells upon stimulation", "upon stimulation by", "stimulation by multiple", "by multiple types", "multiple types of", "types of exogenously", "of exogenously added", "exogenously added dna", "dna takaoka", "takaoka a et", "a et al", "et al 2007", "al 2007 .", "2007 . human", ". human cytomegalovirus", "cytomegalovirus hcmv", "hcmv was", "was shown to", "shown to stimulate", "to stimulate zbp1", "stimulate zbp1 mediated", "zbp1 mediated induction", "induction of irf3", "of irf3 in", "irf3 in human", "in human foreskin", "foreskin defilippis", "defilippis vr et", "vr et al", "et al 2010", "al 2010 .", "2010 . zbp1", ". zbp1 was", "zbp1 was also", "was also implicated", "also implicated in", "implicated in activation", "in activation of", "activation of nf", "of nf kappab", "nf kappab pathways", "kappab pathways in", "pathways in human", "in human embryonic", "human embryonic kidney", "embryonic kidney hek293t", "kidney hek293t cells", "cells kaiser", "kaiser wj et", "wj et al", "et al 2008", "2008 rebsamen", "rebsamen m et", "m et al", "et al 2009", "al 2009 .", "2009 . however", "however the", "the role and", "role and importance", "and importance ofzbp1", "importance ofzbp1 as", "ofzbp1 as dsdna", "as dsdna sensor", "dsdna sensor remain", "sensor remain controversial", "controversial since", "since knocking down", "knocking down zbp1", "down zbp1 expression", "zbp1 expression in", "expression in other", "in other human", "other human or", "human or murine", "or murine cell", "murine cell types", "cell types by", "types by sirna", "by sirna had", "sirna had very", "had very little", "very little effect", "little effect on", "effect on cellular", "on cellular responses", "cellular responses to", "responses to cytosolic", "to cytosolic dna", "dna suggesting", "suggesting the presence", "the presence of", "presence of alternative", "of alternative pathway", "pathway wang", "wang zc et", "zc et al", "2008 lippmann", "lippmann j et", "j et al", "al 2008 .", "2008 . tissue", ". tissue specific", "tissue specific expression", "specific expression of", "expression of human", "of human zbp1", "human zbp1 also", "zbp1 also suggests", "also suggests that", "suggests that zbp1", "that zbp1 may", "zbp1 may function", "may function in", "function in cell", "in cell type", "cell type specific", "type specific way", "way rothenburg", "rothenburg s et", "s et al", "et al 2002", "al 2002 .
              ", "z dna binding protein", "dna binding protein 1", "protein 1 zbp1", "known as dna", "as dna dependent", "dna dependent activator of", "dependent activator of ifn", "activator of ifn regulatory", "of ifn regulatory factors", "regulatory factors dai", "dai was reported", "was reported to initiate", "reported to initiate innate", "to initiate innate immune", "initiate innate immune responses", "innate immune responses in", "immune responses in murine", "responses in murine l929", "in murine l929 cells", "murine l929 cells upon", "l929 cells upon stimulation", "cells upon stimulation by", "upon stimulation by multiple", "stimulation by multiple types", "by multiple types of", "multiple types of exogenously", "types of exogenously added", "of exogenously added dna", "added dna takaoka", "dna takaoka a", "takaoka a et al", "a et al 2007", "et al 2007 .", "al 2007 . human", "2007 . human cytomegalovirus", "human cytomegalovirus hcmv", "hcmv was shown", "was shown to stimulate", "shown to stimulate zbp1", "to stimulate zbp1 mediated", "stimulate zbp1 mediated induction", "zbp1 mediated induction of", "mediated induction of irf3", "induction of irf3 in", "of irf3 in human", "irf3 in human foreskin", "human foreskin defilippis", "foreskin defilippis vr", "defilippis vr et al", "vr et al 2010", "et al 2010 .", "al 2010 . zbp1", "2010 . zbp1 was", ". zbp1 was also", "zbp1 was also implicated", "was also implicated in", "also implicated in activation", "implicated in activation of", "in activation of nf", "activation of nf kappab", "of nf kappab pathways", "nf kappab pathways in", "kappab pathways in human", "pathways in human embryonic", "in human embryonic kidney", "human embryonic kidney hek293t", "embryonic kidney hek293t cells", "hek293t cells kaiser", "cells kaiser wj", "kaiser wj et al", "wj et al 2008", "al 2008 rebsamen", "2008 rebsamen m", "rebsamen m et al", "m et al 2009", "et al 2009 .", "al 2009 . however", ". however the", "however the role", "the role and importance", "role and importance ofzbp1", "and importance ofzbp1 as", "importance ofzbp1 as dsdna", "ofzbp1 as dsdna sensor", "as dsdna sensor remain", "dsdna sensor remain controversial", "remain controversial since", "controversial since knocking", "since knocking down zbp1", "knocking down zbp1 expression", "down zbp1 expression in", "zbp1 expression in other", "expression in other human", "in other human or", "other human or murine", "human or murine cell", "or murine cell types", "murine cell types by", "cell types by sirna", "types by sirna had", "by sirna had very", "sirna had very little", "had very little effect", "very little effect on", "little effect on cellular", "effect on cellular responses", "on cellular responses to", "cellular responses to cytosolic", "responses to cytosolic dna", "cytosolic dna suggesting", "dna suggesting the", "suggesting the presence of", "the presence of alternative", "presence of alternative pathway", "alternative pathway wang", "pathway wang zc", "wang zc et al", "zc et al 2008", "al 2008 lippmann", "2008 lippmann j", "lippmann j et al", "j et al 2008", "et al 2008 .", "al 2008 . tissue", "2008 . tissue specific", ". tissue specific expression", "tissue specific expression of", "specific expression of human", "expression of human zbp1", "of human zbp1 also", "human zbp1 also suggests", "zbp1 also suggests that", "also suggests that zbp1", "suggests that zbp1 may", "that zbp1 may function", "zbp1 may function in", "may function in cell", "function in cell type", "in cell type specific", "cell type specific way", "specific way rothenburg", "way rothenburg s", "rothenburg s et al", "s et al 2002", "et al 2002 .
              ", "z dna binding protein 1", "binding protein 1 zbp1", "zbp1 also known", "also known as dna", "known as dna dependent", "as dna dependent activator", "dna dependent activator of ifn", "dependent activator of ifn regulatory", "activator of ifn regulatory factors", "ifn regulatory factors dai", "factors dai was", "dai was reported to", "was reported to initiate innate", "reported to initiate innate immune", "to initiate innate immune responses", "initiate innate immune responses in", "innate immune responses in murine", "immune responses in murine l929", "responses in murine l929 cells", "in murine l929 cells upon", "murine l929 cells upon stimulation", "l929 cells upon stimulation by", "cells upon stimulation by multiple", "upon stimulation by multiple types", "stimulation by multiple types of", "by multiple types of exogenously", "multiple types of exogenously added", "types of exogenously added dna", "exogenously added dna takaoka", "added dna takaoka a", "dna takaoka a et", "takaoka a et al 2007", "a et al 2007 .", "et al 2007 . human", "al 2007 . human cytomegalovirus", ". human cytomegalovirus hcmv", "cytomegalovirus hcmv was", "hcmv was shown to", "was shown to stimulate zbp1", "shown to stimulate zbp1 mediated", "to stimulate zbp1 mediated induction", "stimulate zbp1 mediated induction of", "zbp1 mediated induction of irf3", "mediated induction of irf3 in", "induction of irf3 in human", "of irf3 in human foreskin", "in human foreskin defilippis", "human foreskin defilippis vr", "foreskin defilippis vr et", "defilippis vr et al 2010", "vr et al 2010 .", "et al 2010 . zbp1", "al 2010 . zbp1 was", "2010 . zbp1 was also", ". zbp1 was also implicated", "zbp1 was also implicated in", "was also implicated in activation", "also implicated in activation of", "implicated in activation of nf", "in activation of nf kappab", "activation of nf kappab pathways", "of nf kappab pathways in", "nf kappab pathways in human", "kappab pathways in human embryonic", "pathways in human embryonic kidney", "in human embryonic kidney hek293t", "human embryonic kidney hek293t cells", "kidney hek293t cells kaiser", "hek293t cells kaiser wj", "cells kaiser wj et", "kaiser wj et al 2008", "et al 2008 rebsamen", "al 2008 rebsamen m", "2008 rebsamen m et", "rebsamen m et al 2009", "m et al 2009 .", "et al 2009 . however", "2009 . however the", ". however the role", "however the role and", "the role and importance ofzbp1", "role and importance ofzbp1 as", "and importance ofzbp1 as dsdna", "importance ofzbp1 as dsdna sensor", "ofzbp1 as dsdna sensor remain", "as dsdna sensor remain controversial", "sensor remain controversial since", "remain controversial since knocking", "controversial since knocking down", "since knocking down zbp1 expression", "knocking down zbp1 expression in", "down zbp1 expression in other", "zbp1 expression in other human", "expression in other human or", "in other human or murine", "other human or murine cell", "human or murine cell types", "or murine cell types by", "murine cell types by sirna", "cell types by sirna had", "types by sirna had very", "by sirna had very little", "sirna had very little effect", "had very little effect on", "very little effect on cellular", "little effect on cellular responses", "effect on cellular responses to", "on cellular responses to cytosolic", "cellular responses to cytosolic dna", "to cytosolic dna suggesting", "cytosolic dna suggesting the", "dna suggesting the presence", "suggesting the presence of alternative", "the presence of alternative pathway", "of alternative pathway wang", "alternative pathway wang zc", "pathway wang zc et", "wang zc et al 2008", "et al 2008 lippmann", "al 2008 lippmann j", "2008 lippmann j et", "lippmann j et al 2008", "j et al 2008 .", "et al 2008 . tissue", "al 2008 . tissue specific", "2008 . tissue specific expression", ". tissue specific expression of", "tissue specific expression of human", "specific expression of human zbp1", "expression of human zbp1 also", "of human zbp1 also suggests", "human zbp1 also suggests that", "zbp1 also suggests that zbp1", "also suggests that zbp1 may", "suggests that zbp1 may function", "that zbp1 may function in", "zbp1 may function in cell", "may function in cell type", "function in cell type specific", "in cell type specific way", "type specific way rothenburg", "specific way rothenburg s", "way rothenburg s et", "rothenburg s et al 2002", "s et al 2002 .
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has been", "has been attributed", "been attributed to", "attributed to the", "to the mitochondrial", "the mitochondrial transcription", "transcription termination factor", "factor mterf", "a 39 kda", "39 kda protein", "kda protein that", "protein that binds", "that binds to", "binds to a", "to a 28", "a 28 base", "28 base pair", "base pair region", "pair region of", "region of mtdna", "of mtdna located", "mtdna located within", "located within the", "within the trnaleu", "the trnaleu uur", "uur gene", "gene at", "at a position", "a position immediately", "position immediately downstream", "immediately downstream of", "downstream of the", "of the rrna", "the rrna 16s", "rrna 16s gene", "fernandez silva et", "silva et al.", "et al. 1997", "1997 kruse", "kruse et al.", "al. 1989", "transcription of the heavy", "the heavy h", "h strand of", "strand of mitochondrial dna", "mitochondrial dna mtdna", "mtdna involves two", "involves two overlapping transcription", "two overlapping transcription units", "units montoyaet", "al. 1982 montoya", "1982 montoya et", "et al. 1983", "al. 1983 .", "1983 . the first", ". the first unit", "the first unit starts", "first unit starts right", "unit starts right upstream", "starts right upstream of", "right upstream of the", "upstream of the trnaphe", "of the trnaphe gene", "the trnaphe gene and", "trnaphe gene and spans", "gene and spans the", "and spans the trnaphe", "the trnaphe rrna", "trnaphe rrna 12s", "rrna 12s rrna", "12s rrna 16s", "rrna 16s and trnaval", "16s and trnaval genes", "trnaval genes initiation", "genes initiation site", "initiation site ih1 .", "site ih1 . the", "ih1 . the other", ". the other starts", "the other starts about", "other starts about 100", "starts about 100 bp", "about 100 bp further", "100 bp further downstream", "further downstream initiation", "downstream initiation site", "ih2 at", "at the boundary between", "the boundary between trnaphe", "boundary between trnaphe and", "between trnaphe and rrna12s", "trnaphe and rrna12s genes", "rrna12s genes and", "genes and produces", "and produces a single", "produces a single polycistronic", "a single polycistronic rna", "single polycistronic rna that", "polycistronic rna that encompasses", "rna that encompasses almost", "that encompasses almost the", "encompasses almost the entire", "almost the entire length", "the entire length of", "entire length of the", "length of the h", "of the h strand.", "the h strand. the", "h strand. the ribosomal", "strand. the ribosomal transcription", "the ribosomal transcription unit", "ribosomal transcription unit is", "transcription unit is transcribed", "unit is transcribed at", "is transcribed at a", "transcribed at a much", "at a much higher", "a much higher rate", "much higher rate compared", "higher rate compared to", "rate compared to the", "compared to the other", "to the other transcription", "the other transcription unit", "other transcription unit and", "transcription unit and control", 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that", "kda protein that binds", "protein that binds to", "that binds to a", "binds to a 28", "to a 28 base", "a 28 base pair", "28 base pair region", "base pair region of", "pair region of mtdna", "region of mtdna located", "of mtdna located within", "mtdna located within the", "located within the trnaleu", "within the trnaleu uur", "trnaleu uur gene", "gene at a", "at a position immediately", "a position immediately downstream", "position immediately downstream of", "immediately downstream of the", "downstream of the rrna", "of the rrna 16s", "the rrna 16s gene", "gene fernandez", "fernandez silva et al.", "silva et al. 1997", "al. 1997 kruse", "1997 kruse et", "et al. 1989", "al. 1989 .", "of the heavy h", "heavy h strand", "h strand of mitochondrial", "of mitochondrial dna mtdna", "dna mtdna involves", "mtdna involves two overlapping", "involves two overlapping transcription units", "transcription units montoyaet", "units montoyaet al.", "montoyaet al. 1982 montoya", "al. 1982 montoya et", "1982 montoya et al.", "montoya et al. 1983", "et al. 1983 .", "al. 1983 . the", "1983 . the first unit", ". the first unit starts", "the first unit starts right", "first unit starts right upstream", "unit starts right upstream of", "starts right upstream of the", "right upstream of the trnaphe", "upstream of the trnaphe gene", "of the trnaphe gene and", "the trnaphe gene and spans", "trnaphe gene and spans the", "gene and spans the trnaphe", "spans the trnaphe rrna", "the trnaphe rrna 12s", "rrna 12s rrna 16s", "12s rrna 16s and", "rrna 16s and trnaval genes", "and trnaval genes initiation", "trnaval genes initiation site", "genes initiation site ih1", "initiation site ih1 . the", "site ih1 . the other", "ih1 . the other starts", ". the other starts about", "the other starts about 100", "other starts about 100 bp", "starts about 100 bp further", "about 100 bp further downstream", "bp further downstream initiation", "further downstream initiation site", "downstream 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"1990 . a central role", ". a central role in", "a central role in the", "central role in the control", "role in the control of", "in the control of termination", "the control of termination has", "control of termination has been", "of termination has been attributed", "termination has been attributed to", "has been attributed to the", "been attributed to the mitochondrial", "attributed to the mitochondrial transcription", "to the mitochondrial transcription termination", "the mitochondrial transcription termination factor", "transcription termination factor mterf", "mterf a 39", "a 39 kda protein that", "39 kda protein that binds", "kda protein that binds to", "protein that binds to a", "that binds to a 28", "binds to a 28 base", "to a 28 base pair", "a 28 base pair region", "28 base pair region of", "base pair region of mtdna", "pair region of mtdna located", "region of mtdna located within", "of mtdna located within the", "mtdna located within the trnaleu", "located within the trnaleu uur", "the trnaleu uur gene", "uur gene at", "gene at a position", "at a position immediately downstream", "a position immediately downstream of", "position immediately downstream of the", "immediately downstream of the rrna", "downstream of the rrna 16s", "of the rrna 16s gene", "16s gene fernandez", "gene fernandez silva", "fernandez silva et al. 1997", "et al. 1997 kruse", "al. 1997 kruse et", "1997 kruse et al.", "kruse et al. 1989", "et al. 1989 ." ] }, { "record_id": "GLY_000594_1_1590", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "163685", "r hsa", "hsa 163685", "r hsa 163685" ] }, { "record_id": "GLY_000594_1_1590", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "integration of", "of energy", "energy metabolism", "integration of energy", "of energy metabolism", "integration of energy metabolism", "many hormones", "hormones that", "that affect", "affect individual", "individual physiological", "physiological processes", "processes including", "including the", "the regulation", "regulation of", "of appetite", "and oxidation", "oxidation of", "of foodstuffs", "foodstuffs influence", "influence energy", "metabolism pathways.", "pathways. while", "while insulin", "insulin mediates", "mediates the", "the storage", "storage of", "of excess", "excess nutrients", "glucagon is", "is involved", "involved in", "in the", "the mobilization", "mobilization of", "energy resources", "resources in", "in response", "response to", "to low", "low blood", "blood glucose", "glucose levels", "principally by", "by stimulating", "stimulating hepatic", "hepatic glucose", "glucose output.", "output. small", "small doses", "doses of", "of glucagon", "glucagon are", "are sufficient", "sufficient to", "to induce", "induce significant", "significant glucose", "glucose elevations.", "elevations. these", "these hormone", "hormone driven", "driven regulatory", "regulatory pathways", "pathways enable", "enable the", "the body", "body to", "to sense", "sense and", "and respond", "respond to", "to changed", "changed amounts", "amounts of", "of nutrients", "nutrients in", "the blood", "blood and", "and demands", "demands for", "for energy.
              glucagon", "energy.
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              pathway", "pathways:
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              pathway", "secretion.
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              pathway 3.", "3. pka", "pka mediated", "mediated phosphorylation:pka", "phosphorylation:pka phosphorylates", "phosphorylates key", "key enzymes", "6 phosphofructo", "phosphofructo 2", "2 kinase", "kinase /fructose", "/fructose 2", "2 6", "6 bisphosphatase", "pf2k pase", "at serine", "serine 36", "and regulatory", "regulatory proteins", "carbohydrate response", "response element", "element binding", "binding protein", "serine 196", "196 and", "and threonine", "threonine 666.
              in", "666.
              in brief", "insulin to", "receptor leads", "leads to", "to increased", "increased protein", "protein phosphatase", "phosphatase activity", "activity and", "and to", "to hydrolysis", "hydrolysis of", "of camp", "camp by", "by camp", "camp phosphodiesterase.", "phosphodiesterase. these", "these events", "events counteract", "counteract the", "the regulatory", "regulatory effects", "effects of", "of glucagon.
              pathway", "glucagon.
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              pathway 5:", "5: amp", "amp kinase", "mediated response", "to high", "high amp:atp", "amp:atp ratio:", "ratio: in", "to diet", "diet with", "with high", "high fat", "fat content", "content or", "or low", "low energy", "energy levels", "the cytosolic", "cytosolic amp:atp", "amp:atp ratio", "ratio is", "is increased.", "increased. amp", "amp triggers", "triggers a", "a complicated", "complicated cascade", "cascade of", "of events.", "events. in", "module we", "we have", "have annotated", "annotated only", "only the", "the phosphorylation", "phosphorylation of", "of chrebp", "chrebp by", "by ampk", "ampk at", "serine 568", "which inactivates", "inactivates this", "this transcription", "transcription factor.
              pathway", "factor.
              pathway 6:", "6: dephosphorylation", "dephosphorylation of", "of key", "metabolic factors", "factors by", "by pp2a:", "pp2a: xy", "              xy 5", "p activated", "activated pp2a", "pp2a efficiently", "efficiently dephosphorylates", "dephosphorylates phosphorylated", "phosphorylated pf2k", "pase resulting", "resulting in", "the higher", "higher output", "output of", "of f", "f 2", "6 p2", "p2 that", "that enhances", "enhances pfk", "pfk activity", "activity in", "the glycolytic", "glycolytic pathway.", "pathway. pp2a", "pp2a also", "also dephosphorylates", "and thus", "thus activates", "cytosolic and", "and nuclear", "nuclear chrebp.
              pathway", "chrebp.
              pathway 7:", "7: transcriptional", "transcriptional activation", "of metabolic", "metabolic genes", "genes by", "by chrebp:", "chrebp:               dephosphorylated", "dephosphorylated chrebp", "chrebp activates", "activates the", "the transcription", "transcription of", "of genes", "genes involved", "in glucose", "glucose metabolism", "metabolism such", "such as", "as pyruvate", "pyruvate kinase", "and lipogenic", "lipogenic genes", "genes such", "as acetyl", "acetyl coa", "coa carboxylase", "fatty acid", "acid synthetase", "acyl coa", "coa synthase", "synthase and", "and glycerol", "glycerol phosphate", "phosphate acyl", "acyl transferase.", "many hormones that", "hormones that affect", "that affect individual", "affect individual physiological", "individual physiological processes", "physiological processes including", "processes including the", "including the regulation", "the regulation of", "regulation of appetite", "appetite absorption", "absorption transport", "transport and", "and oxidation of", "oxidation of foodstuffs", "of foodstuffs influence", "foodstuffs influence energy", "influence energy metabolism", "energy metabolism pathways.", "metabolism pathways. while", "pathways. while insulin", "while insulin mediates", "insulin mediates the", "mediates the storage", "the storage of", "storage of excess", "of excess nutrients", "nutrients glucagon", "glucagon is involved", "is involved in", "involved in the", "in the mobilization", "the mobilization of", "mobilization of energy", "of energy resources", "energy resources in", "resources in response", "in response to", "response to low", "to low blood", "low blood glucose", "blood glucose levels", "levels principally", "principally by stimulating", "by stimulating hepatic", "stimulating hepatic glucose", "hepatic glucose output.", "glucose output. small", "output. small doses", "small doses of", "doses of glucagon", "of glucagon are", "glucagon are sufficient", "are sufficient to", "sufficient to induce", "to induce significant", "induce significant glucose", "significant glucose elevations.", "glucose elevations. these", "elevations. these hormone", "these hormone driven", "hormone driven regulatory", "driven regulatory pathways", "regulatory pathways enable", "pathways enable the", "enable the body", "the body to", "body to sense", "to sense and", "sense and respond", "and respond to", "respond to changed", "to changed amounts", "changed amounts of", "amounts of nutrients", "of nutrients in", "nutrients in the", "in the blood", "the blood and", "blood and demands", "and demands for", "demands for energy.
              glucagon", "for energy.
              glucagon and", "energy.
              glucagon and insulin", "and insulin act", "insulin act through", "act through various", "through various metabolites", "various metabolites and", "metabolites and enzymes", "and enzymes that", "enzymes that target", "that target specific", "target specific steps", "specific steps in", "steps in metabolic", "in metabolic pathways", "metabolic pathways for", "pathways for sugar", "for sugar and", "sugar and fatty", "and fatty acids.", "fatty acids. the", "acids. the processes", "the processes responsible", "processes responsible for", "responsible for the", "for the long", "the long term", "long term control", "term control of", "control of fat", "of fat synthesis", "fat synthesis and", "synthesis and short", "and short term", "short term control", "control of glycolysis", "of glycolysis by", "glycolysis by key", "by key metabolic", "key metabolic products", "metabolic products and", "products and enzymes", "and enzymes are", "enzymes are annotated", "are annotated in", "annotated in this", "in this module", "this module as", "module as seven", "as seven specific", "seven specific pathways:
              pathway", "specific pathways:
              pathway 1.", "pathways:
              pathway 1. regulation", "1. regulation of", "regulation of insulin", "of insulin secretion.
              pathway", "insulin secretion.
              pathway 2.", "secretion.
              pathway 2. glucagon", "2. glucagon signalling", "glucagon signalling in", "signalling in metabolic", "in metabolic pathways:", "metabolic pathways:               in", "pathways:               in response", "glucose pancreatic", "pancreatic alpha cells", "alpha cells release", "cells release glucagon.", "release glucagon. the", "glucagon. the binding", "the binding of", "binding of glucagon", "of glucagon to", "glucagon to its", "to its receptor", "its receptor results", "receptor results in", "results in increased", "in increased camp", "increased camp synthesis", "and protein kinase", "protein kinase a", "a pka", "pka activation.
              pathway", "activation.
              pathway 3. pka", "3. pka mediated", "pka mediated phosphorylation:pka", "mediated phosphorylation:              pka phosphorylates", "phosphorylation:pka phosphorylates key", "phosphorylates key enzymes", "enzymes e.g.", "e.g. 6", "6 phosphofructo 2", "phosphofructo 2 kinase", "2 kinase /fructose", "kinase /fructose 2", "/fructose 2 6", "2 6 bisphosphatase", "bisphosphatase pf2k", "pase at", "at serine 36", "36 and", "and regulatory proteins", "proteins e.g.", "e.g. carbohydrate", "carbohydrate response element", "response element binding", "element binding protein", "protein chrebp", "chrebp at", "at serine 196", "serine 196 and", "196 and threonine", "and threonine 666.
              in", "threonine 666.
              in brief", "brief the", "binding of insulin", "of insulin to", "insulin to its", "its receptor leads", "receptor leads to", "leads to increased", "to increased protein", "increased protein phosphatase", "protein phosphatase activity", "phosphatase activity and", "activity and to", "and to hydrolysis", "to hydrolysis of", "hydrolysis of camp", "of camp by", "camp by camp", "by camp phosphodiesterase.", "camp phosphodiesterase. these", "phosphodiesterase. these events", "these events counteract", "events counteract the", "counteract the regulatory", "the regulatory effects", "regulatory effects of", "effects of glucagon.
              pathway", "of glucagon.
              pathway 4:", "glucagon.
              pathway 4: insulin", "4: insulin stimulates", "insulin stimulates increased", "stimulates increased synthesis", "increased synthesis of", "synthesis of xylulose", "of xylulose 5", "xylulose 5 phosphate", "phosphate xy", "xy 5 p", "5 p .", "p               . activation", "              . activation of", "activation of the", "of the insulin", "the insulin receptor", "insulin receptor results", "receptor results indirectly", "results indirectly in", "indirectly in increased", "in increased xy", "increased xy 5", "5 p synthesis", "p synthesis from", "synthesis from glyceraldehyde", "from glyceraldehyde 3", "glyceraldehyde 3 phosphate", "3 phosphate and", "phosphate and fructose", "and fructose 6", "fructose 6 phosphate.", "6 phosphate. xy", "phosphate. xy 5", "p a", "a metabolite of", "metabolite of the", "of the pentose", "the pentose phosphate", "pentose phosphate pathway", "pathway stimulates", "stimulates protein phosphatase", "phosphatase pp2a.
              pathway", "pp2a.
              pathway 5: amp", "5: amp kinase", "kinase ampk", "ampk mediated", "mediated response to", "response to high", "to high amp:atp", "high amp:atp ratio:", "amp:atp ratio:               in", "ratio: in response", "response to diet", "to diet with", "diet with high", "with high fat", "high fat content", "fat content or", "content or low", "or low energy", "low energy levels", "levels the", "the cytosolic amp:atp", "cytosolic amp:atp ratio", "amp:atp ratio is", "ratio is increased.", "is increased. amp", "increased. amp triggers", "amp triggers a", "triggers a complicated", "a complicated cascade", "complicated cascade of", "cascade of events.", "of events. in", "events. in this", "this module we", "module we have", "we have annotated", "have annotated only", "annotated only the", "only the phosphorylation", "the phosphorylation of", "phosphorylation of chrebp", "of chrebp by", "chrebp by ampk", "by ampk at", "ampk at serine", "at serine 568", "568 which", "which inactivates this", "inactivates this transcription", "this transcription factor.
              pathway", "transcription factor.
              pathway 6:", "factor.
              pathway 6: dephosphorylation", "6: dephosphorylation of", "dephosphorylation of key", "of key metabolic", "key metabolic factors", "metabolic factors by", "factors by pp2a:", "by pp2a: xy", "pp2a:               xy 5", "              xy 5 p", "5 p activated", "p activated pp2a", "activated pp2a efficiently", "pp2a efficiently dephosphorylates", "efficiently dephosphorylates phosphorylated", "dephosphorylates phosphorylated pf2k", "phosphorylated pf2k pase", "pf2k pase resulting", "pase resulting in", "resulting in the", "in the higher", "the higher output", "higher output of", "output of f", "of f 2", "f 2 6", "2 6 p2", "6 p2 that", "p2 that enhances", "that enhances pfk", "enhances pfk activity", "pfk activity in", "activity in the", "in the glycolytic", "the glycolytic pathway.", "glycolytic pathway. pp2a", "pathway. pp2a also", "pp2a also dephosphorylates", "dephosphorylates and", "and thus activates", "activates cytosolic", "cytosolic and nuclear", "and nuclear chrebp.
              pathway", "nuclear chrebp.
              pathway 7:", "chrebp.
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              glucagon", "demands for energy.
              glucagon and", "for energy.
              glucagon and insulin", "energy.
              glucagon and insulin act", "and insulin act through", "insulin act through various", "act through various metabolites", "through various metabolites and", "various metabolites and enzymes", "metabolites and enzymes that", "and enzymes that target", "enzymes that target specific", "that target specific steps", "target specific steps in", "specific steps in metabolic", "steps in metabolic pathways", "in metabolic pathways for", "metabolic pathways for sugar", "pathways for sugar and", "for sugar and fatty", "sugar and fatty acids.", "and fatty acids. the", "fatty acids. the processes", "acids. the processes responsible", "the processes responsible for", "processes responsible for the", "responsible for the long", "for the long term", "the long term control", "long term control of", "term control of fat", "control of fat synthesis", "of fat synthesis and", "fat synthesis and short", "synthesis and short term", "and short term control", "short term control of", "term control of glycolysis", "control of glycolysis by", "of glycolysis by key", "glycolysis by key metabolic", "by key metabolic products", "key metabolic products and", "metabolic products and enzymes", "products and enzymes are", "and enzymes are annotated", "enzymes are annotated in", "are annotated in this", "annotated in this module", "in this module as", "this module as seven", "module as seven specific", "as seven specific pathways:
              pathway", "seven specific pathways:
              pathway 1.", "specific pathways:
              pathway 1. regulation", "pathways:
              pathway 1. regulation of", "1. regulation of insulin", "regulation of insulin secretion.
              pathway", "of insulin secretion.
              pathway 2.", "insulin secretion.
              pathway 2. glucagon", "secretion.
              pathway 2. glucagon signalling", "2. glucagon signalling in", "glucagon signalling in metabolic", "signalling in metabolic pathways:", "in metabolic pathways:               in", "metabolic pathways:               in response", "pathways:               in response to", "blood glucose pancreatic", "glucose pancreatic alpha", "pancreatic alpha cells release", "alpha cells release glucagon.", "cells release glucagon. the", "release glucagon. the binding", "glucagon. the binding of", "the binding of glucagon", "binding of glucagon to", "of glucagon to its", "glucagon to its receptor", "to its receptor results", "its receptor results in", "receptor results in increased", "results in increased camp", "in increased camp synthesis", "camp synthesis and", "synthesis and protein", "and protein kinase a", "kinase a pka", "pka activation.
              pathway 3.", "activation.
              pathway 3. pka mediated", "3. pka mediated phosphorylation:pka", "pka mediated phosphorylation:              pka phosphorylates", "mediated phosphorylation:pka phosphorylates key", "phosphorylation:pka phosphorylates key enzymes", "key enzymes e.g.", "e.g. 6 phosphofructo", "6 phosphofructo 2 kinase", "phosphofructo 2 kinase /fructose", "2 kinase /fructose 2", "kinase /fructose 2 6", "/fructose 2 6 bisphosphatase", "6 bisphosphatase pf2k", "bisphosphatase pf2k pase", "pf2k pase at", "pase at serine", "serine 36 and", "36 and regulatory", "regulatory proteins e.g.", "e.g. carbohydrate response", "carbohydrate response element binding", "response element binding protein", "binding protein chrebp", "chrebp at serine", "at serine 196 and", "serine 196 and threonine", "196 and threonine 666.
              in", "and threonine 666.
              in brief", "666.
              in brief the", "brief the binding", "the binding of insulin", "binding of insulin to", "of insulin to its", "insulin to its receptor", "to its receptor leads", "its receptor leads to", "receptor leads to increased", "leads to increased protein", "to increased protein phosphatase", "increased protein phosphatase activity", "protein phosphatase activity and", "phosphatase activity and to", "activity and to hydrolysis", "and to hydrolysis of", "to hydrolysis of camp", "hydrolysis of camp by", "of camp by camp", "camp by camp phosphodiesterase.", "by camp phosphodiesterase. these", "camp phosphodiesterase. these events", "phosphodiesterase. these events counteract", "these events counteract the", "events counteract the regulatory", "counteract the regulatory effects", "the regulatory effects of", "regulatory effects of glucagon.
              pathway", "effects of glucagon.
              pathway 4:", "of glucagon.
              pathway 4: insulin", "glucagon.
              pathway 4: insulin stimulates", "4: insulin stimulates increased", "insulin stimulates increased synthesis", "stimulates increased synthesis of", "increased synthesis of xylulose", "synthesis of xylulose 5", "of xylulose 5 phosphate", "5 phosphate xy", "phosphate xy 5", "xy 5 p .", "5 p               . activation", "p               . activation of", "              . activation of the", "activation of the insulin", "of the insulin receptor", "the insulin receptor results", "insulin receptor results indirectly", "receptor results indirectly in", "results indirectly in increased", "indirectly in increased xy", "in increased xy 5", "increased xy 5 p", "xy 5 p synthesis", "5 p synthesis from", "p synthesis from glyceraldehyde", "synthesis from glyceraldehyde 3", "from glyceraldehyde 3 phosphate", "glyceraldehyde 3 phosphate and", "3 phosphate and fructose", "phosphate and fructose 6", "and fructose 6 phosphate.", "fructose 6 phosphate. xy", "6 phosphate. xy 5", "phosphate. xy 5 p", "5 p a", "p a metabolite", "a metabolite of the", "metabolite of the pentose", "of the pentose phosphate", "the pentose phosphate pathway", "phosphate pathway stimulates", "pathway stimulates protein", "protein phosphatase pp2a.
              pathway", "phosphatase pp2a.
              pathway 5:", "pp2a.
              pathway 5: amp kinase", "amp kinase ampk", "ampk mediated response", "mediated response to high", "response to high amp:atp", "to high amp:atp ratio:", "high amp:atp ratio:               in", "amp:atp ratio:               in response", "ratio: in response to", "in response to diet", "response to diet with", "to diet with high", "diet with high fat", "with high fat content", "high fat content or", "fat content or low", "content or low energy", "or low energy levels", "energy levels the", "levels the cytosolic", "the cytosolic amp:atp ratio", "cytosolic amp:atp ratio is", "amp:atp ratio is increased.", "ratio is increased. amp", "is increased. amp triggers", "increased. amp triggers a", "amp triggers a complicated", "triggers a complicated cascade", "a complicated cascade of", "complicated cascade of events.", "cascade of events. in", "of events. in this", "events. in this module", "in this module we", "this module we have", "module we have annotated", "we have annotated only", "have annotated only the", "annotated only the phosphorylation", "only the phosphorylation of", "the phosphorylation of chrebp", "phosphorylation of chrebp by", "of chrebp by ampk", "chrebp by ampk at", "by ampk at serine", "ampk at serine 568", "serine 568 which", "568 which inactivates", "which inactivates this transcription", "inactivates this transcription factor.
              pathway", "this transcription factor.
              pathway 6:", "transcription factor.
              pathway 6: dephosphorylation", "factor.
              pathway 6: dephosphorylation of", "6: dephosphorylation of key", "dephosphorylation of key metabolic", "of key metabolic factors", "key metabolic factors by", "metabolic factors by pp2a:", "factors by pp2a: xy", "by pp2a:               xy 5", "pp2a:               xy 5 p", "              xy 5 p activated", "5 p activated pp2a", "p activated pp2a efficiently", "activated pp2a efficiently dephosphorylates", "pp2a efficiently dephosphorylates phosphorylated", "efficiently dephosphorylates phosphorylated pf2k", "dephosphorylates phosphorylated pf2k pase", "phosphorylated pf2k pase resulting", "pf2k pase resulting in", "pase resulting in the", "resulting in the higher", "in the higher output", "the higher output of", "higher output of f", "output of f 2", "of f 2 6", "f 2 6 p2", "2 6 p2 that", "6 p2 that enhances", "p2 that enhances pfk", "that enhances pfk activity", "enhances pfk activity in", "pfk activity in the", "activity in the glycolytic", "in the glycolytic pathway.", "the glycolytic pathway. pp2a", "glycolytic pathway. pp2a also", "pathway. pp2a also dephosphorylates", "also dephosphorylates and", "dephosphorylates and thus", "thus activates cytosolic", "activates cytosolic and", "cytosolic and nuclear chrebp.
              pathway", "and nuclear chrebp.
              pathway 7:", "nuclear chrebp.
              pathway 7: transcriptional", "chrebp.
              pathway 7: transcriptional activation", "7: transcriptional activation of", "transcriptional activation of metabolic", "activation of metabolic genes", "of metabolic genes by", "metabolic genes by chrebp:", "genes by chrebp:               dephosphorylated", "by chrebp:               dephosphorylated chrebp", "chrebp:               dephosphorylated chrebp activates", "dephosphorylated chrebp activates the", "chrebp activates the transcription", "activates the transcription of", "the transcription of genes", "transcription of genes involved", "of genes involved in", "genes involved in glucose", "involved in glucose metabolism", "in glucose metabolism such", "glucose metabolism such as", "metabolism such as pyruvate", "such as pyruvate kinase", "pyruvate kinase and", "kinase and lipogenic", "and lipogenic genes such", "lipogenic genes such as", "genes such as acetyl", "such as acetyl coa", "as acetyl coa carboxylase", "coa carboxylase fatty", "carboxylase fatty acid", "acid synthetase acyl", "synthetase acyl coa", "acyl coa synthase and", "coa synthase and glycerol", "synthase and glycerol phosphate", "and glycerol phosphate acyl", "glycerol phosphate acyl transferase.", "many hormones that affect individual", "hormones that affect individual physiological", "that affect individual physiological processes", "affect individual physiological processes including", "individual physiological processes including the", "physiological processes including the regulation", "processes including the regulation of", "including the regulation of appetite", "regulation of appetite absorption", "appetite absorption transport", "absorption transport and", "transport and oxidation of", "and oxidation of foodstuffs influence", "oxidation of foodstuffs influence energy", "of foodstuffs influence energy metabolism", "foodstuffs influence energy metabolism pathways.", "influence energy metabolism pathways. while", "energy metabolism pathways. while insulin", "metabolism pathways. while insulin mediates", "pathways. while insulin mediates the", "while insulin mediates the storage", "insulin mediates the storage of", "mediates the storage of excess", "the storage of excess nutrients", "of excess nutrients glucagon", "excess nutrients glucagon is", "nutrients glucagon is involved", "glucagon is involved in the", "is involved in the mobilization", "involved in the mobilization of", "in the mobilization of energy", "the mobilization of energy resources", "mobilization of energy resources in", "of energy resources in response", "energy resources in response to", "resources in response to low", "in response to low blood", "response to low blood glucose", "to low blood glucose levels", "blood glucose levels principally", "glucose levels principally by", "levels principally by stimulating", "principally by stimulating hepatic glucose", "by stimulating hepatic glucose output.", "stimulating hepatic glucose output. small", "hepatic glucose output. small doses", "glucose output. small doses of", "output. small doses of glucagon", "small doses of glucagon are", "doses of glucagon are sufficient", "of glucagon are sufficient to", "glucagon are sufficient to induce", "are sufficient to induce significant", "sufficient to induce significant glucose", "to induce significant glucose elevations.", "induce significant glucose elevations. these", "significant glucose elevations. these hormone", "glucose elevations. these hormone driven", "elevations. these hormone driven regulatory", "these hormone driven regulatory pathways", "hormone driven regulatory pathways enable", "driven regulatory pathways enable the", "regulatory pathways enable the body", "pathways enable the body to", "enable the body to sense", "the body to sense and", "body to sense and respond", "to sense and respond to", "sense and respond to changed", "and respond to changed amounts", "respond to changed amounts of", "to changed amounts of nutrients", "changed amounts of nutrients in", "amounts of nutrients in the", "of nutrients in the blood", "nutrients in the blood and", "in the blood and demands", "the blood and demands for", "blood and demands for energy.
              glucagon", "and demands for energy.
              glucagon and", "demands for energy.
              glucagon and insulin", "for energy.
              glucagon and insulin act", "energy.
              glucagon and insulin act through", "and insulin act through various", "insulin act through various metabolites", "act through various metabolites and", "through various metabolites and enzymes", "various metabolites and enzymes that", "metabolites and enzymes that target", "and enzymes that target specific", "enzymes that target specific steps", "that target specific steps in", "target specific steps in metabolic", "specific steps in metabolic pathways", "steps in metabolic pathways for", "in metabolic pathways for sugar", "metabolic pathways for sugar and", "pathways for sugar and fatty", "for sugar and fatty acids.", "sugar and fatty acids. the", "and fatty acids. the processes", "fatty acids. the processes responsible", "acids. the processes responsible for", "the processes responsible for the", "processes responsible for the long", "responsible for the long term", "for the long term control", "the long term control of", "long term control of fat", "term control of fat synthesis", "control of fat synthesis and", "of fat synthesis and short", "fat synthesis and short term", "synthesis and short term control", "and short term control of", "short term control of glycolysis", "term control of glycolysis by", "control of glycolysis by key", "of glycolysis by key metabolic", "glycolysis by key metabolic products", "by key metabolic products and", "key metabolic products and enzymes", "metabolic products and enzymes are", "products and enzymes are annotated", "and enzymes are annotated in", "enzymes are annotated in this", "are annotated in this module", "annotated in this module as", "in this module as seven", "this module as seven specific", "module as seven specific pathways:
              pathway", "as seven specific pathways:
              pathway 1.", "seven specific pathways:
              pathway 1. regulation", "specific pathways:
              pathway 1. regulation of", "pathways:
              pathway 1. regulation of insulin", "1. regulation of insulin secretion.
              pathway", "regulation of insulin secretion.
              pathway 2.", "of insulin secretion.
              pathway 2. glucagon", "insulin secretion.
              pathway 2. glucagon signalling", "secretion.
              pathway 2. glucagon signalling in", "2. glucagon signalling in metabolic", "glucagon signalling in metabolic pathways:", "signalling in metabolic pathways:               in", "in metabolic pathways:               in response", "metabolic pathways:               in response to", "pathways:               in response to low", "low blood glucose pancreatic", "blood glucose pancreatic alpha", "glucose pancreatic alpha cells", "pancreatic alpha cells release glucagon.", "alpha cells release glucagon. the", "cells release glucagon. the binding", "release glucagon. the binding of", "glucagon. the binding of glucagon", "the binding of glucagon to", "binding of glucagon to its", "of glucagon to its receptor", "glucagon to its receptor results", "to its receptor results in", "its receptor results in increased", "receptor results in increased camp", "results in increased camp synthesis", "increased camp synthesis and", "camp synthesis and protein", "synthesis and protein kinase", "protein kinase a pka", "a pka activation.
              pathway", "pka activation.
              pathway 3. pka", "activation.
              pathway 3. pka mediated phosphorylation:pka", "3. pka mediated phosphorylation:              pka phosphorylates", "pka mediated phosphorylation:              pka phosphorylates key", "mediated phosphorylation:pka phosphorylates key enzymes", "phosphorylates key enzymes e.g.", "enzymes e.g. 6", "e.g. 6 phosphofructo 2", "6 phosphofructo 2 kinase /fructose", "phosphofructo 2 kinase /fructose 2", "2 kinase /fructose 2 6", "kinase /fructose 2 6 bisphosphatase", "2 6 bisphosphatase pf2k", "6 bisphosphatase pf2k pase", "pf2k pase at serine", "pase at serine 36", "at serine 36 and", "serine 36 and regulatory", "36 and regulatory proteins", "and regulatory proteins e.g.", "proteins e.g. carbohydrate", "e.g. carbohydrate response element", "carbohydrate response element binding protein", "element binding protein chrebp", "protein chrebp at", "chrebp at serine 196", "at serine 196 and threonine", "serine 196 and threonine 666.
              in", "196 and threonine 666.
              in brief", "threonine 666.
              in brief the", "666.
              in brief the binding", "brief the binding of", "the binding of insulin to", "binding of insulin to its", "of insulin to its receptor", "insulin to its receptor leads", "to its receptor leads to", "its receptor leads to increased", "receptor leads to increased protein", "leads to increased protein phosphatase", "to increased protein phosphatase activity", "increased protein phosphatase activity and", "protein phosphatase activity and to", "phosphatase activity and to hydrolysis", "activity and to hydrolysis of", "and to hydrolysis of camp", "to hydrolysis of camp by", "hydrolysis of camp by camp", "of camp by camp phosphodiesterase.", "camp by camp phosphodiesterase. these", "by camp phosphodiesterase. these events", "camp phosphodiesterase. these events counteract", "phosphodiesterase. these events counteract the", "these events counteract the regulatory", "events counteract the regulatory effects", "counteract the regulatory effects of", "the regulatory effects of glucagon.
              pathway", "regulatory effects of glucagon.
              pathway 4:", "effects of glucagon.
              pathway 4: insulin", "of glucagon.
              pathway 4: insulin stimulates", "glucagon.
              pathway 4: insulin stimulates increased", "4: insulin stimulates increased synthesis", "insulin stimulates increased synthesis of", "stimulates increased synthesis of xylulose", "increased synthesis of xylulose 5", "synthesis of xylulose 5 phosphate", "xylulose 5 phosphate xy", "5 phosphate xy 5", "phosphate xy 5 p", "xy 5 p . activation", "5 p               . activation of", "p               . activation of the", "              . activation of the insulin", "activation of the insulin receptor", "of the insulin receptor results", "the insulin receptor results indirectly", "insulin receptor results indirectly in", "receptor results indirectly in increased", "results indirectly in increased xy", "indirectly in increased xy 5", "in increased xy 5 p", "increased xy 5 p synthesis", "xy 5 p synthesis from", "5 p synthesis from glyceraldehyde", "p synthesis from glyceraldehyde 3", "synthesis from glyceraldehyde 3 phosphate", "from glyceraldehyde 3 phosphate and", "glyceraldehyde 3 phosphate and fructose", "3 phosphate and fructose 6", "phosphate and fructose 6 phosphate.", "and fructose 6 phosphate. xy", "fructose 6 phosphate. xy 5", "6 phosphate. xy 5 p", "xy 5 p a", "5 p a metabolite", "p a metabolite of", "a metabolite of the pentose", "metabolite of the pentose phosphate", "of the pentose phosphate pathway", "pentose phosphate pathway stimulates", "phosphate pathway stimulates protein", "pathway stimulates protein phosphatase", "stimulates protein phosphatase pp2a.
              pathway", "protein phosphatase pp2a.
              pathway 5:", "phosphatase pp2a.
              pathway 5: amp", "5: amp kinase ampk", "kinase ampk mediated", "ampk mediated response to", "mediated response to high amp:atp", "response to high amp:atp ratio:", "to high amp:atp ratio:               in", "high amp:atp ratio:               in response", "amp:atp ratio:               in response to", "ratio: in response to diet", "in response to diet with", "response to diet with high", "to diet with high fat", "diet with high fat content", "with high fat content or", "high fat content or low", "fat content or low energy", "content or low energy levels", "low energy levels the", "energy levels the cytosolic", "levels the cytosolic amp:atp", "the cytosolic amp:atp ratio is", "cytosolic amp:atp ratio is increased.", "amp:atp ratio is increased. amp", "ratio is increased. amp triggers", "is increased. amp triggers a", "increased. amp triggers a complicated", "amp triggers a complicated cascade", "triggers a complicated cascade of", "a complicated cascade of events.", "complicated cascade of events. in", "cascade of events. in this", "of events. in this module", "events. in this module we", "in this module we have", "this module we have annotated", "module we have annotated only", "we have annotated only the", "have annotated only the phosphorylation", "annotated only the phosphorylation of", "only the phosphorylation of chrebp", "the phosphorylation of chrebp by", "phosphorylation of chrebp by ampk", "of chrebp by ampk at", "chrebp by ampk at serine", "by ampk at serine 568", "at serine 568 which", "serine 568 which inactivates", "568 which inactivates this", "which inactivates this transcription factor.
              pathway", "inactivates this transcription factor.
              pathway 6:", "this transcription factor.
              pathway 6: dephosphorylation", "transcription factor.
              pathway 6: dephosphorylation of", "factor.
              pathway 6: dephosphorylation of key", "6: dephosphorylation of key metabolic", "dephosphorylation of key metabolic factors", "of key metabolic factors by", "key metabolic factors by pp2a:", "metabolic factors by pp2a: xy", "factors by pp2a:               xy 5", "by pp2a:               xy 5 p", "pp2a:               xy 5 p activated", "              xy 5 p activated pp2a", "5 p activated pp2a efficiently", "p activated pp2a efficiently dephosphorylates", "activated pp2a efficiently dephosphorylates phosphorylated", "pp2a efficiently dephosphorylates phosphorylated pf2k", "efficiently dephosphorylates phosphorylated pf2k pase", "dephosphorylates phosphorylated pf2k pase resulting", "phosphorylated pf2k pase resulting in", "pf2k pase resulting in the", "pase resulting in the higher", "resulting in the higher output", "in the higher output of", "the higher output of f", "higher output of f 2", "output of f 2 6", "of f 2 6 p2", "f 2 6 p2 that", "2 6 p2 that enhances", "6 p2 that enhances pfk", "p2 that enhances pfk activity", "that enhances pfk activity in", "enhances pfk activity in the", "pfk activity in the glycolytic", "activity in the glycolytic pathway.", "in the glycolytic pathway. pp2a", "the glycolytic pathway. pp2a also", "glycolytic pathway. pp2a also dephosphorylates", "pp2a also dephosphorylates and", "also dephosphorylates and thus", "dephosphorylates and thus activates", "and thus activates cytosolic", "thus activates cytosolic and", "activates cytosolic and nuclear", "cytosolic and nuclear chrebp.
              pathway 7:", "and nuclear chrebp.
              pathway 7: transcriptional", "nuclear chrebp.
              pathway 7: transcriptional activation", "chrebp.
              pathway 7: transcriptional activation of", "7: transcriptional activation of metabolic", "transcriptional activation of metabolic genes", "activation of metabolic genes by", "of metabolic genes by chrebp:", "metabolic genes by chrebp:               dephosphorylated", "genes by chrebp:               dephosphorylated chrebp", "by chrebp:               dephosphorylated chrebp activates", "chrebp: dephosphorylated chrebp activates the", "dephosphorylated chrebp activates the transcription", "chrebp activates the transcription of", "activates the transcription of genes", "the transcription of genes involved", "transcription of genes involved in", "of genes involved in glucose", "genes involved in glucose metabolism", "involved in glucose metabolism such", "in glucose metabolism such as", "glucose metabolism such as pyruvate", "metabolism such as pyruvate kinase", "as pyruvate kinase and", "pyruvate kinase and lipogenic", "kinase and lipogenic genes", "and lipogenic genes such as", "lipogenic genes such as acetyl", "genes such as acetyl coa", "such as acetyl coa carboxylase", "acetyl coa carboxylase fatty", "coa carboxylase fatty acid", "carboxylase fatty acid synthetase", "fatty acid synthetase acyl", "acid synthetase acyl coa", "synthetase acyl coa synthase", "acyl coa synthase and glycerol", "coa synthase and glycerol phosphate", "synthase and glycerol phosphate acyl", "and glycerol phosphate acyl transferase." ] }, { "record_id": "GLY_000594_1_1591", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "163754", "r hsa", "hsa 163754", "r hsa 163754" ] }, { "record_id": "GLY_000594_1_1591", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "insulin effects", "effects increased", "increased synthesis", "synthesis of", "of xylulose", "xylulose 5", "5 phosphate", "insulin effects increased", "effects increased synthesis", "increased synthesis of", "synthesis of xylulose", "of 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demonstrated", "protein myd88 demonstrated reduced", "myd88 demonstrated reduced responses", "demonstrated reduced responses to", "reduced responses to in", "responses to in vivo", "to in vivo infection", "in vivo infection with", "vivo infection with vsv", "with vsv lund", "vsv lund jm", "lund jm et al.", "jm et al. 2004", "mouse adapted sars cov", "adapted sars cov 1", "cov 1 sheahan", "1 sheahan et", "sheahan et al. 2008", "al. 2008 totura", "2008 totura et", "et al. 2015", "al. 2015 .", "2015 . upon middle", ". upon middle east", "upon middle east respiratory", "middle east respiratory syndrome", "east respiratory syndrome related", "respiratory syndrome related coronavirus", "related coronavirus mers", "coronavirus mers cov", "mers cov infection", "infection lack of", "lack of myd88 signaling", "of myd88 signaling resulted", "myd88 signaling resulted in", "signaling resulted in delayed", "resulted in delayed viral", "in delayed viral clearance", "delayed viral clearance and", "viral clearance and increased", "clearance and increased lung", "and increased lung pathology", "increased lung pathology in", "lung pathology in mice", "in mice zhao", "mice zhao et", "zhao et al. 2014", "et al. 2014 .", "al. 2014 . consistently", ". consistently another", "consistently another study", "another study showed that", "study showed that tlr7", "showed that tlr7 /", "tlr7 / mice", "/ mice have", "mice have reduced ifn", "have reduced ifn expression", "reduced ifn expression compared", "ifn expression compared with", "expression compared with wild", "compared with wild type", "with wild type mice", "type mice channappanavar", "mice channappanavar et", "channappanavar et al. 2019", "et al. 2019 .", "al. 2019 . in", "2019 . in addition", "in addition loss", "addition loss of", "loss of function tlr7", "of function tlr7 variants", "function tlr7 variants identified", "tlr7 variants identified in", "variants identified in the", "identified in the patients", "in the patients with", "the patients with sars", "patients with sars cov", "with sars cov 2", "cov 2 covid", "2 covid 19", "covid 19 resulted", "19 resulted in", "resulted in defective upregulation", "in defective upregulation of", "defective upregulation of type", "upregulation of type i", "of type i ifn\u2013related", "type i ifn\u2013related genes", "i ifn\u2013related genes in", "ifn\u2013related genes in the", "genes in the tlr7", "in the tlr7 pathway", "tlr7 pathway figure", "pathway figure 3", "figure 3 in", "3 in response", "in response to the", "response to the tlr7", "to the tlr7 agonist", "the tlr7 agonist imiquimod", "tlr7 agonist imiquimod as", "agonist imiquimod as compared", "imiquimod as compared with", "as compared with controls", "with controls van", "controls van der", "van der made ci", "der made ci et", "made ci et al.", "ci et al. 2020", "et al. 2020 .", "al. 2020 . separate", "2020 . separate studies", ". separate studies showed", "separate studies showed that", "studies showed that synthetic", "showed that synthetic imidazoquinoline", "that synthetic imidazoquinoline compounds", "imidazoquinoline compounds e.g.", "compounds e.g. imiquimod", "e.g. imiquimod and r", "imiquimod and r 848", "r 848 low", "848 low molecular", "low molecular weight immune", "molecular weight immune response", "weight immune response modifiers", "immune response modifiers that", "response modifiers that can", "modifiers that can induce", "that can induce the", "can induce the synthesis", "induce the synthesis of", "the synthesis of interferon", "synthesis of interferon alpha", "interferon alpha also", "alpha also exert", "also exert their effects", "exert their effects in", "their effects in a", "effects in a myd88", "in a myd88 dependent", "a myd88 dependent fashion", "myd88 dependent fashion through", "dependent fashion through tlr7", "fashion through tlr7 or", "through tlr7 or tlr8", "or tlr8 hemmi", "tlr8 hemmi h", "hemmi h et al.", "h et al. 2002", "al. 2002 jurk", "2002 jurk m", "al. 2002 diebold", "2002 diebold ss", "al. 2004 . some", "2004 . some viruses", ". some viruses utilize", "some viruses utilize multiple", "viruses utilize multiple strategies", "utilize multiple strategies to", "multiple strategies to evade", "strategies to evade antiviral", "to evade antiviral innate", "evade antiviral innate immune", "antiviral innate immune signaling", "immune signaling as", "signaling as is", "as is seen with", "is seen with influenza", "seen with influenza or", "with influenza or sars", "influenza or sars coronaviruses.", "or sars coronaviruses. tlr7", "sars coronaviruses. tlr7 mediated", "coronaviruses. tlr7 mediated innate", "tlr7 mediated innate immunity", "innate immunity for", "immunity for example", "for example was", "example was associated", "was associated with the", "associated with the negative", "with the negative regulation", "the negative regulation through", "negative regulation through removing", "regulation through removing lys63", "through removing lys63 linked", "removing lys63 linked polyubiquitin", "lys63 linked polyubiquitin chains", "linked polyubiquitin chains of", "polyubiquitin chains of traf3/traf6", "chains of traf3/traf6 by", "of traf3/traf6 by papin", "traf3/traf6 by papin like", "by papin like protease", "like protease plpro", "plpro catalytic domain", "catalytic domain of nsp3", "domain of nsp3 from", "of nsp3 from sars", "nsp3 from sars cov", "from sars cov 1", "cov 1 li", "1 li sw", "li sw et al.", "sw et al. 2016", "et al. 2016 .", "al. 2016 . thus", ". thus tlr7", "thus tlr7 and", "tlr7 and tlr8 play", "and tlr8 play a", "tlr8 play a critical", "play a critical role", "a critical role in", "critical role in sensing", "role in sensing of", "in sensing of viral", "sensing of viral ssrna", "of viral ssrna in", "viral ssrna in the", "ssrna in the endosome.", "rna can serve as a", "can serve as a danger", "serve as a danger signal", "a danger signal both", "danger signal both in", "signal both in its", "both in its double stranded", "in its double stranded form", "its double stranded form as", "double stranded form as well", "stranded form as well as", "form as well as single", "as well as single stranded", "well as single stranded rna", "single stranded rna ssrna", "stranded rna ssrna .", "rna ssrna . toll", "ssrna . toll like receptor", ". toll like receptor 7", "like receptor 7 tlr7", "7 tlr7 and", "and tlr8 are endosomal receptors", "tlr8 are endosomal receptors that", "are endosomal receptors that sense", "endosomal receptors that sense ssrna", "receptors that sense ssrna oligonucleotides", "that sense ssrna oligonucleotides containing", "sense ssrna oligonucleotides containing guanosine", "oligonucleotides containing guanosine g", "g and uridine", "uridine u rich", "u rich sequences from", "rich sequences from rna viruses", "from rna viruses jurk", "rna viruses jurk m", "viruses jurk m et", "jurk m et al. 2002", "et al. 2002 heil", "al. 2002 heil f", "2002 heil f et", "heil f et al. 2004", "et al. 2004 diebold", "al. 2004 diebold ss", "2004 diebold ss et", "diebold ss et al. 2004", "et al. 2004 li", "al. 2004 li y", "2004 li y et", "li y et al. 2013", "et al. 2013 reviewed", "al. 2013 reviewed in", "2013 reviewed in lester", "reviewed in lester sn &", "in lester sn & li", "lester sn & li k", "sn & li k 2014", "& li k 2014 .", "li k 2014 . tlr7", "k 2014 . tlr7 is", "2014 . tlr7 is primarily", ". tlr7 is primarily expressed", "tlr7 is primarily expressed in", "is primarily expressed in plasmacytoid", "primarily expressed in plasmacytoid dendritic", "expressed in plasmacytoid dendritic cells", "plasmacytoid dendritic cells pdcs", "cells pdcs and", "pdcs and to", "and to some extent", "to some extent in", "some extent in b", "extent in b cells", "in b cells monocytes", "b cells monocytes and", "cells monocytes and macrophages", "monocytes and macrophages whereas", "and macrophages whereas tlr8", "macrophages whereas tlr8 is", "whereas tlr8 is mostly expressed", "tlr8 is mostly expressed in", "is mostly expressed in monocytes", "expressed in monocytes macrophages", "in monocytes macrophages and", "monocytes macrophages and myeloid", "macrophages and myeloid dcs. upon", "and myeloid dcs. upon engagement", "myeloid dcs. upon engagement of", "dcs. upon engagement of ssrnas", "upon engagement of ssrnas in", "engagement of ssrnas in endosomes", "ssrnas in endosomes tlr7/8", "in endosomes tlr7/8 initiate", "endosomes tlr7/8 initiate the", "tlr7/8 initiate the myeloid differentiation", "initiate the myeloid differentiation factor", "the myeloid differentiation factor 88", "differentiation factor 88 myd88", "88 myd88 dependent", "dependent pathway culminating in", "pathway culminating in synthesis", "culminating in synthesis of type", "in synthesis of type i", "synthesis of type i and", "of type i and type", "type i and type iii", "i and type iii ifns", "and type iii ifns and", "type iii ifns and proinflammatory", "iii ifns and proinflammatory mediators", "ifns and proinflammatory mediators via", "and proinflammatory mediators via activation", "proinflammatory mediators via activation of", "mediators via activation of ifn", "via activation of ifn regulatory", "activation of ifn regulatory factors", "ifn regulatory factors irf7", "factors irf7 irf5", "irf7 irf5 and", "irf5 and nf kappab", "and nf kappab respectively", "kappab respectively depending", "respectively depending on the", "depending on the cell type", "the cell type takaoka", "cell type takaoka a", "type takaoka a et", "a et al. 2005", "al. 2005 heinz", "2005 heinz lx et", "lx et al. 2020", "al. 2020 reviewed", "2020 reviewed in lester", "k 2014 . tlr7 and", "2014 . tlr7 and tlr8", ". tlr7 and tlr8 are", "tlr7 and tlr8 are able", "and tlr8 are able to", "tlr8 are able to detect", "are able to detect gu", "able to detect gu rich", "to detect gu rich ssrna", "detect gu rich ssrna sequences", "gu rich ssrna sequences from", "rich ssrna sequences from the", "ssrna sequences from the viral", "sequences from the viral genomes", "from the viral genomes of", "the viral genomes of influenza", "genomes of influenza human", "of influenza human immunodeficiency", "influenza human immunodeficiency virus", "immunodeficiency virus 1 hiv", "virus 1 hiv 1", "hiv 1 vesicular", "1 vesicular stomatitis", "vesicular stomatitis virus vsv", "vsv coxsackie b", "coxsackie b virus coronavirus", "b virus coronavirus and", "virus coronavirus and flaviviruses", "coronavirus and flaviviruses hepatitis", "and flaviviruses hepatitis c", "flaviviruses hepatitis c virus", "hepatitis c virus hcv", "c virus hcv and", "virus hcv and west", "hcv and west nile virus", "west nile virus wnv", "virus wnv reviewed", "wnv reviewed in lester", "li k 2014 . specifically", "2014 . specifically gu", ". specifically gu rich", "specifically gu rich ssrna", "gu rich ssrna oligonucleotides derived", "rich ssrna oligonucleotides derived from", "ssrna oligonucleotides derived from hiv", "oligonucleotides derived from hiv 1", "from hiv 1 for", "hiv 1 for example", "for example stimulate dendritic", "example stimulate dendritic cells", "stimulate dendritic cells dc", "cells dc and", "dc and macrophages to", "and macrophages to secrete interferon", "macrophages to secrete interferon alpha", "to secrete interferon alpha and", "secrete interferon alpha and proinflammatory", "alpha and proinflammatory as", "and proinflammatory as well", "proinflammatory as well as", "well as regulatory cytokines", "regulatory cytokines heil", "cytokines heil f et", "f et al. 2004 .", "et al. 2004 . this", "al. 2004 . this has", "2004 . this has been", ". this has been found", "this has been found to", "has been found to be", "been found to be mediated", "found to be mediated by", "to be mediated by tlr7", "mediated by tlr7 as", "by tlr7 as well", "tlr7 as well as", "as well as tlr8. similarly", "as tlr8. similarly severe", "tlr8. similarly severe acute", "similarly severe acute respiratory", "severe acute respiratory syndrome associated", "acute respiratory syndrome associated coronavirus", "respiratory syndrome associated coronavirus type", "syndrome associated coronavirus type 1", "coronavirus type 1 sars", "type 1 sars cov", "1 sars cov 1", "sars cov 1 gu", "cov 1 gu rich", "1 gu rich ssrnas", "gu rich ssrnas had powerful", "rich ssrnas had powerful immunostimulatory", "ssrnas had powerful immunostimulatory activities", "had powerful immunostimulatory activities in", "powerful immunostimulatory activities in mononuclear", "immunostimulatory activities in mononuclear phagocytes", "activities in mononuclear phagocytes to", "in mononuclear phagocytes to induce", "mononuclear phagocytes to induce considerable", "phagocytes to induce considerable level", "to induce considerable level of", "induce considerable level of pro", "considerable level of pro inflammatory", "level of pro inflammatory cytokine", "of pro inflammatory cytokine tnf", "pro inflammatory cytokine tnf a", "cytokine tnf a il", "tnf a il 6", "a il 6 and", "il 6 and il 12", "6 and il 12 release", "and il 12 release via", "il 12 release via the", "12 release via the tlr7", "release via the tlr7 and", "via the tlr7 and tlr8", "tlr7 and tlr8 li", "and tlr8 li y", "tlr8 li y et", "y et al. 2013 .", "et al. 2013 . further", "2013 . further mice", ". further mice deficient", "further mice deficient in", "mice deficient in either tlr7", "deficient in either tlr7 or", "in either tlr7 or the", "either tlr7 or the tlr", "tlr7 or the tlr adaptor", "or the tlr adaptor protein", "the tlr adaptor protein myd88", "tlr adaptor protein myd88 demonstrated", "adaptor protein myd88 demonstrated reduced", "protein myd88 demonstrated reduced responses", "myd88 demonstrated reduced responses to", "demonstrated reduced responses to in", "reduced responses to in vivo", "responses to in vivo infection", "to in vivo infection with", "in vivo infection with vsv", "infection with vsv lund", "with vsv lund jm", "vsv lund jm et", "lund jm et al. 2004", "2004 mouse", "mouse adapted sars cov 1", "sars cov 1 sheahan", "cov 1 sheahan et", "1 sheahan et al.", "et al. 2008 totura", "al. 2008 totura et", "2008 totura et al.", "totura et al. 2015", "et al. 2015 .", "al. 2015 . upon", "2015 . upon middle east", ". upon middle east respiratory", "upon middle east respiratory syndrome", "middle east respiratory syndrome related", "east respiratory syndrome related coronavirus", "syndrome related coronavirus mers", "related coronavirus mers cov", "cov infection lack", "infection lack of myd88", "lack of myd88 signaling resulted", "of myd88 signaling resulted in", "myd88 signaling resulted in delayed", "signaling resulted in delayed viral", "resulted in delayed viral clearance", "in delayed viral clearance and", "delayed viral clearance and increased", "viral clearance and increased lung", "clearance and increased lung pathology", "and increased lung pathology in", "increased lung pathology in mice", "pathology in mice zhao", "in mice zhao et", "mice zhao et al.", "zhao et al. 2014 .", "et al. 2014 . consistently", "2014 . consistently another", ". consistently another study", "consistently another study showed", "another study showed that tlr7", "study showed that tlr7 /", "that tlr7 / mice", "tlr7 / mice have", "/ mice have reduced", "mice have reduced ifn expression", "have reduced ifn expression compared", "reduced ifn expression compared with", "ifn expression compared with wild", "expression compared with wild type", "compared with wild type mice", "wild type mice channappanavar", "type mice channappanavar et", "mice channappanavar et al.", "channappanavar et al. 2019 .", "et al. 2019 . in", "al. 2019 . in addition", ". in addition loss", "in addition loss of", "addition loss of function", "loss of function tlr7 variants", "of function tlr7 variants identified", "function tlr7 variants identified in", "tlr7 variants identified in the", "variants identified in the patients", "identified in the patients 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              o fucosyl", "notch.

              o fucosyl transferase", "

              o fucosyl transferase pofut1", "o fucosyl transferase pofut1 fucosylates", "fucosyl transferase pofut1 fucosylates notch", "transferase pofut1 fucosylates notch serine", "pofut1 fucosylates notch serine and", "fucosylates notch serine and threonine", "notch serine and threonine residues", "serine and threonine residues that", "and threonine residues that conform", "threonine residues that conform to", "residues that conform to the", "that conform to the consensus", "conform to the consensus sequence", "to the consensus sequence c2", "the consensus sequence c2 x", "consensus sequence c2 x 4", "sequence c2 x 4 5", "x 4 5 s/t", "4 5 s/t c3", "s/t c3 where c2", "c3 where c2 and", "where c2 and c3 are", "c2 and c3 are the", "and c3 are the second", "c3 are the second and", "are the second and third", "the second and third cysteine", "second and third cysteine residue", "and third cysteine residue within", "third cysteine residue within the", "cysteine residue within the egf", "residue within the egf repeat", "the egf repeat and", "egf repeat and x", "repeat and x 4", "x 4 5 is", "4 5 is four", "5 is four to", "is four to five amino", "four to five amino acid", "to five amino acid residues", "five amino acid residues of", "amino acid residues of any", "acid residues of any type", "of any type yao", "any type yao et", "type yao et al.", "et al. 2011 stahl", "al. 2011 stahl et", "2011 stahl et al.", "et al. 2008 wang", "al. 2008 wang et", "2008 wang et al.", "et al. 2001 shao", "al. 2001 shao et", "2001 shao et al.", "shao et al. 2003 .", "et al. 2003 .
              ", "al. 2003 .

              o", "2003 .

              o glucosyl", ".

              o glucosyl transferase", "

              o glucosyl transferase poglut1", "glucosyl transferase poglut1 mammalian", "transferase poglut1 mammalian homolog", "poglut1 mammalian homolog of", "mammalian homolog of the drosophila", "homolog of the drosophila enzyme", "of the drosophila enzyme rumi", "drosophila enzyme rumi adds", "enzyme rumi adds a", "rumi adds a glucosyl", "adds a glucosyl group to", "a glucosyl group to conserved", "glucosyl group to conserved serine", "group to conserved serine residues", "to conserved serine residues within", "conserved serine residues within the", "serine residues within the egf", "residues within the egf repeats", "within the egf repeats of", "the egf repeats of notch.", "egf repeats of notch. the", "repeats of notch. the consensus", "of notch. the consensus sequence", "notch. the consensus sequence for", "the consensus sequence for poglut1", "consensus sequence for poglut1 mediated", "sequence for poglut1 mediated glucosylation", "for poglut1 mediated glucosylation is", "poglut1 mediated glucosylation is c1", "mediated glucosylation is c1 x", "glucosylation is c1 x s", "is c1 x s x", "c1 x s x p", "x s x p c2", "x p c2 where", "p c2 where c1", "c2 where c1 and", "where c1 and c2 are", "c1 and c2 are the", "and c2 are the first", "c2 are the first and", "are the first and second", "the first and second cysteine", "first and second cysteine residue", "and second cysteine residue in", "second cysteine residue in the", "cysteine residue in the egf", "residue in the egf repeat", "the egf repeat respectively", "repeat respectively while", "respectively while x represents", "while x represents any amino", "x represents any amino acid", "any amino acid acar", "amino acid acar et", "acid acar et al.", "et al. 2008 fernandez", "al. 2008 fernandez valdivia", "2008 fernandez valdivia et", "fernandez valdivia et al. 2011", "valdivia et al. 2011 .", "et al. 2011 . both", "al. 2011 . both fucosylation", "2011 . both fucosylation and", ". both fucosylation and glucosylation", "both fucosylation and glucosylation of", "fucosylation and glucosylation of notch", "and glucosylation of notch receptor", "glucosylation of notch receptor precursors", "of notch receptor precursors are", "notch receptor precursors are essential", "receptor precursors are essential for", "precursors are essential for functionality." ] }, { "record_id": "GLY_000594_1_1604", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "197264", "r hsa", "hsa 197264", "r hsa 197264" ] }, { "record_id": "GLY_000594_1_1604", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nicotinamide salvage", "levels are", "are modulated", "modulated by", "by the", "the action", "action of", "of three", "three enzymes", "enzymes involved", "involved in", "in nicotinamide", "nicotinamide salvaging.", "salvaging. they", "they are", "are nicotinamide", "nicotinamide deaminase", "nicotinamide phosphoribosyltransferase", "phosphoribosyltransferase and", "and nicotinate", "nicotinate phosphoribosyltransferase.", "phosphoribosyltransferase. these", "these enzymes", "enzymes are", "are poorly", "poorly characterized", "characterized in", "in humans", "depsite their", "their importance", "importance in", "in nam", "nam utilization", "magni et", "et al.", "al. 2004", "2004 .", ". although", "although not", "not a", "a salvage", "salvage reaction", "nam levels", "levels can", "can also", "also be", "be regulated", "regulated by", "by nicotinamide", "nicotinamide n", "n methyltransferase", "a potential", "potential regulator", "regulator of", "of diet", "diet induced", "induced obesity", "kraus et", "al. 2014", "2014 .", "nicotinamide nam", "levels are modulated", "are modulated by", "modulated by the", "by the action", "the action of", "action of three", "of three enzymes", "three enzymes involved", "enzymes involved in", "involved in nicotinamide", "in nicotinamide salvaging.", "nicotinamide salvaging. they", "salvaging. they are", "they are nicotinamide", "are nicotinamide deaminase", "deaminase nicotinamide", "nicotinamide phosphoribosyltransferase and", "phosphoribosyltransferase and nicotinate", "and nicotinate phosphoribosyltransferase.", "nicotinate phosphoribosyltransferase. these", "phosphoribosyltransferase. these enzymes", "these enzymes are", "enzymes are poorly", "are poorly characterized", "poorly characterized in", "characterized in humans", "humans depsite", "depsite their importance", "their importance in", "importance in nam", "in nam utilization", "utilization magni", "magni et al.", "et al. 2004", "al. 2004 .", "2004 . although", ". although not", "although not a", "not a salvage", "a salvage reaction", "reaction nam", "nam levels can", "levels can also", "can also be", "also be regulated", "be regulated by", "regulated by nicotinamide", "by nicotinamide n", "nicotinamide n methyltransferase", "methyltransferase nnmt", "a potential regulator", "potential regulator of", "regulator of diet", "of diet induced", "diet induced obesity", "obesity kraus", "kraus et al.", "et al. 2014", "al. 2014 .", "nam levels are", "levels are modulated by", "are modulated by the", "modulated by the action", "by the action of", "the action of three", "action of three enzymes", "of three enzymes involved", "three enzymes involved in", "enzymes involved in nicotinamide", "involved in nicotinamide salvaging.", "in nicotinamide salvaging. they", "nicotinamide salvaging. they are", "salvaging. they are nicotinamide", "they are nicotinamide deaminase", "nicotinamide deaminase nicotinamide", "deaminase nicotinamide phosphoribosyltransferase", "nicotinamide phosphoribosyltransferase and nicotinate", "phosphoribosyltransferase and nicotinate phosphoribosyltransferase.", "and nicotinate phosphoribosyltransferase. these", "nicotinate phosphoribosyltransferase. these enzymes", "phosphoribosyltransferase. these enzymes are", "these enzymes are poorly", "enzymes are poorly characterized", "are poorly characterized in", "poorly characterized in humans", "in humans depsite", "humans depsite their", "depsite their importance in", "their importance in nam", "importance in nam utilization", "nam utilization magni", "utilization magni et", "magni et al. 2004", "et al. 2004 .", "al. 2004 . although", "2004 . although not", ". although not a", "although not a salvage", "not a salvage reaction", "salvage reaction nam", "reaction nam levels", "nam levels can also", "levels can also be", "can also be regulated", "also be regulated by", "be regulated by nicotinamide", "regulated by nicotinamide n", "by nicotinamide n methyltransferase", "n methyltransferase nnmt", "nnmt a", "a potential regulator of", "potential regulator of diet", "regulator of diet induced", "of diet induced obesity", "induced obesity kraus", "obesity kraus et", "kraus et al. 2014", "et al. 2014 .", "nicotinamide nam levels", "nam levels are modulated", "levels are modulated by the", "are modulated by the action", "modulated by the action of", "by the action of three", "the action of three enzymes", "action of three enzymes involved", "of three enzymes involved in", "three enzymes involved in nicotinamide", "enzymes involved in nicotinamide salvaging.", "involved in nicotinamide salvaging. they", "in nicotinamide salvaging. they are", "nicotinamide salvaging. they are nicotinamide", "salvaging. they are nicotinamide deaminase", "are nicotinamide deaminase nicotinamide", "nicotinamide deaminase nicotinamide phosphoribosyltransferase", "deaminase nicotinamide phosphoribosyltransferase and", "nicotinamide phosphoribosyltransferase and nicotinate phosphoribosyltransferase.", "phosphoribosyltransferase and nicotinate phosphoribosyltransferase. these", "and nicotinate phosphoribosyltransferase. these enzymes", "nicotinate phosphoribosyltransferase. these enzymes are", "phosphoribosyltransferase. these enzymes are poorly", "these enzymes are poorly characterized", "enzymes are poorly characterized in", "are poorly characterized in humans", "characterized in humans depsite", "in humans depsite their", "humans depsite their importance", "depsite their importance in nam", "their importance in nam utilization", "in nam utilization magni", "nam utilization magni et", "utilization magni et al.", "magni et al. 2004 .", "et al. 2004 . although", "al. 2004 . although not", "2004 . although not a", ". although not a salvage", "although not a salvage reaction", "a salvage reaction nam", "salvage reaction nam levels", "reaction nam levels can", "nam levels can also be", "levels can also be regulated", "can also be regulated by", "also be regulated by nicotinamide", "be regulated by nicotinamide n", "regulated by nicotinamide n methyltransferase", "nicotinamide n methyltransferase nnmt", "nnmt a potential", "a potential regulator of diet", "potential regulator of diet induced", "regulator of diet induced obesity", "diet induced obesity kraus", "induced obesity kraus et", "obesity kraus et al.", "kraus et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1605", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "198765", "r hsa", "hsa 198765", "r hsa 198765" ] }, { "record_id": "GLY_000594_1_1605", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signalling to", "to erk5", "signalling to erk5", "the location", "location of", "of neurotrophin", "neurotrophin stimulation", "stimulation appears", "appears to", "to determine", "determine the", "the nature", "nature of", "of the", "the transcriptional", "transcriptional response", "response through", "through differential", "differential uses", "uses of", "of individual", "individual map", "map kinases.", "kinases. the", "the erk5", "erk5 pathway", "pathway has", "has a", "a unique", "unique function", "function in", "in retrograde", "retrograde signalling", "in contrast", "which mediate", "mediate nuclear", "nuclear responses", "responses following", "following direct", "direct cell", "cell body", "body stimulation", "does not", "not transmit", "transmit a", "a retrograde", "retrograde signal.", "following neurotrophin", "stimulation of", "of distal", "distal axons", "phosphorylated trk", "trk receptors", "receptors are", "are endocytosed", "endocytosed and", "and transported", "transported to", "to the", "the cell", "cell bodies", "where mek5", "mek5 phosphorylates", "phosphorylates erk5", "leading to", "erk5 nuclear", "nuclear translocation", "phosphorylation of", "of transcription", "transcription factors", "and neuronal", "neuronal survival.", "survival. in", "bodies causes", "causes concurrent", "concurrent activation", "activation and", "and nuclear", "nuclear transport", "transport of", "of erk1/2", "erk1/2 as", "as well", "well as", "as erk5.", "erk5. several", "several distinctive", "distinctive features", "features of", "pathway might", "might be", "be important", "important for", "for retrograde", "retrograde signalling.", "signalling. the", "erk5 cascade", "cascade does", "not depend", "depend on", "on activation", "activation of", "the g", "g protein", "protein ras.", "ras. instead", "this pathway", "pathway may", "may use", "use other", "other g", "g proteins", "proteins such", "such as", "as rap", "rap that", "that are", "are associated", "associated with", "with vesicles", "or may", "may not", "not require", "require any", "any g", "protein intermediate.", "intermediate. another", "another distinctive", "distinctive feature", "feature is", "is that", "that the", "the mek5", "mek5 isoform", "which is", "is expressed", "expressed in", "in the", "the nervous", "nervous system", "exhibits a", "a punctate", "punctate staining", "staining pattern", "suggesting a", "a vesicular", "vesicular localization.", "localization. erk5", "erk5 itself", "itself significantly", "significantly differs", "differs from", "from erk1/2", "and its", "its substrate", "substrate specificity", "specificity also", "also differs", "from erk1/2.", "erk1/2. for", "for instance", "erk5 directly", "directly activates", "activates transcription", "including mef2", "are not", "not phosphorylated", "phosphorylated by", "by erk1/2.", "erk1/2. conversely", "but not", "not erk5", "activate transcription", "factors such", "as elk1", "elk1 and", "and mitf.", "the location of", "location of neurotrophin", "of neurotrophin stimulation", "neurotrophin stimulation appears", "stimulation appears to", "appears to determine", "to determine the", "determine the nature", "the nature of", "nature of the", "of the transcriptional", "the transcriptional response", "transcriptional response through", "response through differential", "through differential uses", "differential uses of", "uses of individual", "of individual map", "individual map kinases.", "map kinases. the", "kinases. the erk5", "the erk5 pathway", "erk5 pathway has", "pathway has a", "has a unique", "a unique function", "unique function in", "function in retrograde", "in retrograde signalling", "signalling in", "contrast erk1/2", "erk1/2 which", "which mediate nuclear", "mediate nuclear responses", "nuclear responses following", "responses following direct", "following direct cell", "direct cell body", "cell body stimulation", "stimulation does", "does not transmit", "not transmit a", "transmit a retrograde", "a retrograde signal.", "signal. following", "following neurotrophin stimulation", "neurotrophin stimulation of", "stimulation of distal", "of distal axons", "axons phosphorylated", "phosphorylated trk receptors", "trk receptors are", "receptors are endocytosed", "are endocytosed and", "endocytosed and transported", "and transported to", "transported to the", "to the cell", "the cell bodies", "bodies where", "where mek5 phosphorylates", "mek5 phosphorylates erk5", "erk5 leading", "leading to erk5", "to erk5 nuclear", "erk5 nuclear translocation", "phosphorylation of transcription", "of transcription factors", "factors and", "and neuronal survival.", "neuronal survival. in", "survival. in contrast", "contrast neurotrophin", "stimulation of the", "of the cell", "cell bodies causes", "bodies causes concurrent", "causes concurrent activation", "concurrent activation and", "activation and nuclear", "and nuclear transport", "nuclear transport of", "transport of erk1/2", "of erk1/2 as", "erk1/2 as well", "as well as", "well as erk5.", "as erk5. several", "erk5. several distinctive", "several distinctive features", "distinctive features of", "features of the", "of the erk5", "erk5 pathway might", "pathway might be", "might be important", "be important for", "important for retrograde", "for retrograde signalling.", "retrograde signalling. the", "signalling. the erk5", "the erk5 cascade", "erk5 cascade does", "cascade does not", "does not depend", "not depend on", "depend on activation", "on activation of", "activation of the", "of the g", "the g protein", "g protein ras.", "protein ras. instead", "instead this", "this pathway may", "pathway may use", "may use other", "use other g", "other g proteins", "g proteins such", "proteins such as", "such as rap", "as rap that", "rap that are", "that are associated", "are associated with", "associated with vesicles", "vesicles or", "or may not", "may not require", "not require any", "require any g", "any g protein", "g protein intermediate.", "protein intermediate. another", "intermediate. another distinctive", "another distinctive feature", "distinctive feature is", "feature is that", "is that the", "that the mek5", "the mek5 isoform", "isoform which", "which is expressed", "is expressed in", "expressed in the", "in the nervous", "the nervous system", "system exhibits", "exhibits a punctate", "a punctate staining", "punctate staining pattern", "pattern suggesting", "suggesting a vesicular", "a vesicular localization.", "vesicular localization. erk5", "localization. erk5 itself", "erk5 itself significantly", "itself significantly differs", "significantly differs from", "differs from erk1/2", "erk1/2 and", "and its substrate", "its substrate specificity", "substrate specificity also", "specificity also differs", "also differs from", "differs from erk1/2.", "from erk1/2. for", "erk1/2. for instance", "instance erk5", "erk5 directly activates", "directly activates transcription", "activates transcription factors", "factors including", "mef2 that", "that are not", "are not phosphorylated", "not phosphorylated by", "phosphorylated by erk1/2.", "by erk1/2. conversely", "conversely erk1/2", "erk1/2 but", "but not erk5", "erk5 activate", "activate transcription factors", "transcription factors such", "factors such as", "such as elk1", "as elk1 and", "elk1 and mitf.", "the location of neurotrophin", "location of neurotrophin stimulation", "of neurotrophin stimulation appears", "neurotrophin stimulation appears to", "stimulation appears to determine", "appears to determine the", "to determine the nature", "determine the nature of", "the nature of the", "nature of the transcriptional", "of the transcriptional response", "the transcriptional response through", "transcriptional response through differential", "response through differential uses", "through differential uses of", "differential uses of individual", "uses of individual map", "of individual map kinases.", "individual map kinases. the", "map kinases. the erk5", "kinases. the erk5 pathway", "the erk5 pathway has", "erk5 pathway has a", "pathway has a unique", "has a unique function", "a unique function in", "unique function in retrograde", "function in retrograde signalling", "retrograde signalling in", "signalling in contrast", "in contrast erk1/2", "erk1/2 which mediate", "which mediate nuclear responses", "mediate nuclear responses following", "nuclear responses following direct", "responses following direct cell", "following direct cell body", "direct cell body stimulation", "body stimulation does", "stimulation does not", "does not transmit a", "not transmit a retrograde", "transmit a retrograde signal.", "retrograde signal. following", "signal. following neurotrophin", "following neurotrophin stimulation of", "neurotrophin stimulation of distal", "stimulation of distal axons", "distal axons phosphorylated", "axons phosphorylated trk", "phosphorylated trk receptors are", "trk receptors are endocytosed", "receptors are endocytosed and", "are endocytosed and transported", "endocytosed and transported to", "and transported to the", "transported to the cell", "to the cell bodies", "cell bodies where", "bodies where mek5", "where mek5 phosphorylates erk5", "phosphorylates erk5 leading", "erk5 leading to", "leading to erk5 nuclear", "to erk5 nuclear translocation", "phosphorylation of transcription factors", "transcription factors and", "factors and neuronal", "and neuronal survival. in", "neuronal survival. in contrast", "in contrast neurotrophin", "contrast neurotrophin stimulation", "neurotrophin stimulation of the", "stimulation of the cell", "of the cell bodies", "the cell bodies causes", "cell bodies causes concurrent", "bodies causes concurrent activation", "causes concurrent activation and", "concurrent activation and nuclear", "activation and nuclear transport", "and nuclear transport of", "nuclear transport of erk1/2", "transport of erk1/2 as", "of erk1/2 as well", "erk1/2 as well as", "as well as erk5.", "well as erk5. several", "as erk5. several distinctive", "erk5. several distinctive features", "several distinctive features of", "distinctive features of the", "features of the erk5", "of the erk5 pathway", "the erk5 pathway might", "erk5 pathway might be", "pathway might be important", "might be important for", "be important for retrograde", "important for retrograde signalling.", "for retrograde signalling. the", "retrograde signalling. the erk5", "signalling. the erk5 cascade", "the erk5 cascade does", "erk5 cascade does not", "cascade does not depend", "does not depend on", "not depend on activation", "depend on activation of", "on activation of the", "activation of the g", "of the g protein", "the g protein ras.", "g protein ras. instead", "ras. instead this", "instead this pathway", "this pathway may use", "pathway may use other", "may use other g", "use other g proteins", "other g proteins such", "g proteins such as", "proteins such as rap", "such as rap that", "as rap that are", "rap that are associated", "that are associated with", "are associated with vesicles", "with vesicles or", "vesicles or may", "or may not require", "may not require any", "not require any g", "require any g protein", "any g protein intermediate.", "g protein intermediate. another", "protein intermediate. another distinctive", "intermediate. another distinctive feature", "another distinctive feature is", "distinctive feature is that", "feature is that the", "is that the mek5", "that the mek5 isoform", "mek5 isoform which", "isoform which is", "which is expressed in", "is expressed in the", "expressed in the nervous", "in the nervous system", "nervous system exhibits", "system exhibits a", "exhibits a punctate staining", "a punctate staining pattern", "staining pattern suggesting", "pattern suggesting a", "suggesting a vesicular localization.", "a vesicular localization. erk5", "vesicular localization. erk5 itself", "localization. erk5 itself significantly", "erk5 itself significantly differs", "itself significantly differs from", "significantly differs from erk1/2", "from erk1/2 and", "erk1/2 and its", "and its substrate specificity", "its substrate specificity also", "substrate specificity also differs", "specificity also differs from", "also differs from erk1/2.", "differs from erk1/2. for", "from erk1/2. for instance", "for instance erk5", "instance erk5 directly", "erk5 directly activates transcription", "directly activates transcription factors", "transcription factors including", "factors including mef2", "including mef2 that", "mef2 that are", "that are not phosphorylated", "are not phosphorylated by", "not phosphorylated by erk1/2.", "phosphorylated by erk1/2. conversely", "erk1/2. conversely erk1/2", "erk1/2 but not", "not erk5 activate", "erk5 activate transcription", "activate transcription factors such", "transcription factors such as", "factors such as elk1", "such as elk1 and", "as elk1 and mitf.", "the location of neurotrophin stimulation", "location of neurotrophin stimulation appears", "of neurotrophin stimulation appears to", "neurotrophin stimulation appears to determine", "stimulation appears to determine the", "appears to determine the nature", "to determine the nature of", "determine the nature of the", "the nature of the transcriptional", "nature of the transcriptional response", "of the transcriptional response through", "the transcriptional response through differential", "transcriptional response through differential uses", "response through differential uses of", "through differential uses of individual", "differential uses of individual map", "uses of individual map kinases.", "of individual map kinases. the", "individual map kinases. the erk5", "map kinases. the erk5 pathway", "kinases. the erk5 pathway has", "the erk5 pathway has a", "erk5 pathway has a unique", "pathway has a unique function", "has a unique function in", "a unique function in retrograde", "unique function in retrograde signalling", "in retrograde signalling in", "retrograde signalling in contrast", "contrast erk1/2 which", "erk1/2 which mediate nuclear", "which mediate nuclear responses following", "mediate nuclear responses following direct", "nuclear responses following direct cell", "responses following direct cell body", "following direct cell body stimulation", "cell body stimulation does", "body stimulation does not", "stimulation does not transmit", "does not transmit a retrograde", "not transmit a retrograde signal.", "a retrograde signal. following", "retrograde signal. following neurotrophin", "signal. following neurotrophin stimulation", "following neurotrophin stimulation of distal", "neurotrophin stimulation of distal axons", "of distal axons phosphorylated", "distal axons phosphorylated trk", "axons phosphorylated trk receptors", "phosphorylated trk receptors are endocytosed", "trk receptors are endocytosed and", "receptors are endocytosed and transported", "are endocytosed and transported to", "endocytosed and transported to the", "and transported to the cell", "transported to the cell bodies", "the cell bodies where", "cell bodies where mek5", "bodies where mek5 phosphorylates", "mek5 phosphorylates erk5 leading", "phosphorylates erk5 leading to", "erk5 leading to erk5", "leading to erk5 nuclear translocation", "translocation phosphorylation", "of transcription factors and", "transcription factors and neuronal", "factors and neuronal survival.", "and neuronal survival. in contrast", "survival. in contrast neurotrophin", "in contrast neurotrophin stimulation", "contrast neurotrophin stimulation of", "neurotrophin stimulation of the cell", "stimulation of the cell bodies", "of the cell bodies causes", "the cell bodies causes concurrent", "cell bodies causes concurrent activation", "bodies causes concurrent activation and", "causes concurrent activation and nuclear", "concurrent activation and nuclear transport", "activation and nuclear transport of", "and nuclear transport of erk1/2", "nuclear transport of erk1/2 as", "transport of erk1/2 as well", "of erk1/2 as well as", "erk1/2 as well as erk5.", "as well as erk5. several", "well as erk5. several distinctive", "as erk5. several distinctive features", "erk5. several distinctive features of", "several distinctive features of the", "distinctive features of the erk5", "features of the erk5 pathway", "of the erk5 pathway might", "the erk5 pathway might be", "erk5 pathway might be important", "pathway might be important for", "might be important for retrograde", "be important for retrograde signalling.", "important for retrograde signalling. the", "for retrograde signalling. the erk5", "retrograde signalling. the erk5 cascade", "signalling. the erk5 cascade does", "the erk5 cascade does not", "erk5 cascade does not depend", "cascade does not depend on", "does not depend on activation", "not depend on activation of", "depend on activation of the", "on activation of the g", "activation of the g protein", "of the g protein ras.", "the g protein ras. instead", "protein ras. instead this", "ras. instead this pathway", "instead this pathway may", "this pathway may use other", "pathway may use other g", "may use other g proteins", "use other g proteins such", "other g proteins such as", "g proteins such as rap", "proteins such as rap that", "such as rap that are", "as rap that are associated", "rap that are associated with", "that are associated with vesicles", "associated with vesicles or", "with vesicles or may", "vesicles or may not", "or may not require any", "may not require any g", "not require any g protein", "require any g protein intermediate.", "any g protein intermediate. another", "g protein intermediate. another distinctive", "protein intermediate. another distinctive feature", "intermediate. another distinctive feature is", "another distinctive feature is that", "distinctive feature is that the", "feature is that the mek5", "is that the mek5 isoform", "the mek5 isoform which", "mek5 isoform which is", "isoform which is expressed", "which is expressed in the", "is expressed in the nervous", "expressed in the nervous system", "the nervous system exhibits", "nervous system exhibits a", "system exhibits a punctate", "exhibits a punctate staining pattern", "punctate staining pattern suggesting", "staining pattern suggesting a", "pattern suggesting a vesicular", "suggesting a vesicular localization. erk5", "a vesicular localization. erk5 itself", "vesicular localization. erk5 itself significantly", "localization. erk5 itself significantly differs", "erk5 itself significantly differs from", "itself significantly differs from erk1/2", "differs from erk1/2 and", "from erk1/2 and its", "erk1/2 and its substrate", "and its substrate specificity also", "its substrate specificity also differs", "substrate specificity also differs from", "specificity also differs from erk1/2.", "also differs from erk1/2. for", "differs from erk1/2. for instance", "erk1/2. for instance erk5", "for instance erk5 directly", "instance erk5 directly activates", "erk5 directly activates transcription factors", "activates transcription factors including", "transcription factors including mef2", "including mef2 that are", "mef2 that are not", "that are not phosphorylated by", "are not phosphorylated by erk1/2.", "not phosphorylated by erk1/2. conversely", "by erk1/2. conversely erk1/2", "conversely erk1/2 but", "erk1/2 but not erk5", "but not erk5 activate", "not erk5 activate transcription", "erk5 activate transcription factors", "activate transcription factors such as", "transcription factors such as elk1", "factors such as elk1 and", "such as elk1 and mitf." ] }, { "record_id": "GLY_000594_1_1606", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "203754", "r hsa", "hsa 203754", "r hsa 203754" ] }, { "record_id": "GLY_000594_1_1606", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nosip mediated", "mediated enos", "enos trafficking", "nosip mediated enos", "mediated enos trafficking", "nosip mediated enos trafficking", "enos interacting", "interacting protein", "is a", "a 34", "34 kda", "kda nucleocytoplasmic", "nucleocytoplasmic shuttling", "shuttling protein", "protein that", "that binds", "binds to", "to the", "the cooh", "cooh terminal", "terminal region", "amino acids", "acids 366", "366 486", "of the", "the enos", "enos oxygenase", "oxygenase domain.", "this protein", "protein association", "association promotes", 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association", "this protein association promotes translocation", "protein association promotes translocation of", "association promotes translocation of enos", "promotes translocation of enos from", "translocation of enos from the", "of enos from the plasma", "enos from the plasma membrane", "from the plasma membrane caveolae", "the plasma membrane caveolae to", "plasma membrane caveolae to the", "membrane caveolae to the cytoskeleton", "caveolae to the cytoskeleton and", "to the cytoskeleton and inhibits", "the cytoskeleton and inhibits enos", "cytoskeleton and inhibits enos activity.", "inhibits enos activity. studies", "enos activity. studies have", "activity. studies have found", "studies have found that nosip", "have found that nosip accumulates", "found that nosip accumulates in", "that nosip accumulates in the", "nosip accumulates in the cytoplasm", "accumulates in the cytoplasm specifically", "in the cytoplasm specifically during", "the cytoplasm specifically during the", "cytoplasm specifically during the g2", "specifically during the g2 phase", "during the g2 phase of", "the g2 phase of the", "g2 phase of the cell", "phase of the cell cycle." ] }, { "record_id": "GLY_000594_1_1607", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "204626", "r hsa", "hsa 204626", "r hsa 204626" ] }, { "record_id": "GLY_000594_1_1607", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hypusine synthesis", "synthesis from", "from eif5a", "eif5a lysine", "hypusine synthesis from", "synthesis from eif5a", "from eif5a lysine", "hypusine synthesis from eif5a", "synthesis from eif5a lysine", "hypusine synthesis from eif5a lysine", "cytosolic eukaryotic", "eukaryotic translation", "translation initiation", "initiation factor", "factor 5a", "undergoes a", "a unique", "unique two", "two step", "step post", "post translational", "translational modification", "modification at", "at lys", "lys 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and", "402 and transported", "and transported to", "transported to the", "to the nucleus", "the nucleus where", "nucleus where it", "where it accumulates", "it accumulates due", "accumulates due to", "due to the", "to the loss", "the loss of", "loss of its", "of its nuclear", "its nuclear export", "nuclear export signal", "export signal motif", "motif jakobi", "2003 . the", ". the activity", "the activity of", "activity of pak", "of pak 2p34", "pak 2p34 appears", "2p34 appears to", "appears to be", "to be regulated", "be regulated both", "regulated both by", "both by proteosomal", "by proteosomal degradation", "degradation jakobi", "2003 and", "and by", "by association with", "association with the", "with the gtpase", "the gtpase activating", "gtpase activating protein", "activating protein ps", "protein ps gap/", "ps gap/ rhg", "gap/ rhg 10.", "rhg 10. this", "10. this interaction", "interaction inhibits", "inhibits the kinase", "the kinase activity", "kinase activity of", "pak 2p34 and", "2p34 and changes", "and changes the", "changes the localization", "the localization of", "localization of pak", "pak 2p34 from", "2p34 from the", "from the nucleus", "the nucleus to", "nucleus to the", "to the perinuclear", "the perinuclear region", "region koeppel", "koeppel et al.", "pak 2p34 may", "may function", "function in", "in the down", "the down regulation", "down regulation of", "regulation of translation", "of translation initiation", "translation initiation in", "initiation in apoptosis", "in apoptosis through", "apoptosis through phosphorylation", "through phosphorylation of", "phosphorylation of mnk1", "mnk1 orton", "orton et al.", "et al. 2004", "al. 2004 .", "in response to stress", "response to stress signals", "stress signals the", "signals the p21", "the p21 activated protein", "p21 activated protein kinase", "protein kinase pak", "kinase pak 2", "pak 2 stimulates a", "2 stimulates a cell", "stimulates a cell death", "a cell death response", "cell death response characterized", "death response characterized by", "response characterized by increased", "characterized by increased cell", "by increased cell rounding", "increased cell rounding and", "cell rounding and apoptotic", "rounding and apoptotic chromatin", "and apoptotic chromatin condensation", "chromatin condensation see", "condensation see jakobi", "see jakobi et al.", "et al. 2003", "al. 2003 .", "2003 . pak 2", ". pak 2 is", "pak 2 is proteolytically", "2 is proteolytically cleaved", "is proteolytically cleaved by", "proteolytically cleaved by caspase", "cleaved by caspase 3", "by caspase 3 producing", "caspase 3 producing a", "3 producing a constitutively", "producing a constitutively active", "constitutively active fragment", "fragment pak 2p34.", "pak 2p34. following", "2p34. following cleavage", "following cleavage pak", "cleavage pak 2p34", "pak 2p34 is autophosphorylated", "2p34 is autophosphorylated at", "is autophosphorylated at thr", "autophosphorylated at thr 402", "at thr 402 and", "thr 402 and transported", "402 and transported to", "and transported to the", "transported to the nucleus", "to the nucleus where", "the nucleus where it", "nucleus where it accumulates", "where it accumulates due", "it accumulates due to", "accumulates due to the", "due to the loss", "to the loss of", "the loss of its", "loss of its nuclear", "of its nuclear export", "its nuclear export signal", "nuclear export signal motif", "signal motif jakobi", "motif jakobi et", "2003 . the activity", ". the activity of", "the activity of pak", "activity of pak 2p34", "of pak 2p34 appears", "pak 2p34 appears to", "2p34 appears to be", "appears to be regulated", "to be regulated both", "be regulated both by", "regulated both by proteosomal", "both by proteosomal degradation", "proteosomal degradation jakobi", "degradation jakobi et", "and by association", "by association with the", "association with the gtpase", "with the gtpase activating", "the gtpase activating protein", "gtpase activating protein ps", "activating protein ps gap/", "protein ps gap/ rhg", "ps gap/ rhg 10.", "gap/ rhg 10. this", "rhg 10. this interaction", "this interaction inhibits", "interaction inhibits the", "inhibits the kinase activity", "the kinase activity of", "pak 2p34 and changes", "2p34 and changes the", "and changes the localization", "changes the localization of", "the localization of pak", "localization of pak 2p34", "of pak 2p34 from", "pak 2p34 from the", "2p34 from the nucleus", "from the nucleus to", "the nucleus to the", "nucleus to the perinuclear", "to the perinuclear region", "perinuclear region koeppel", "region koeppel et", "2004 . pak", ". pak 2p34", "2p34 may function", "function in the", "in the down regulation", "the down regulation of", "down regulation of translation", "regulation of translation initiation", "of translation initiation in", "translation initiation in apoptosis", "initiation in apoptosis through", "in apoptosis through phosphorylation", "apoptosis through phosphorylation of", "through phosphorylation of mnk1", "of mnk1 orton", "mnk1 orton et", "orton et al. 2004", "et al. 2004 .", "in response to stress signals", "to stress signals the", "stress signals the p21", "signals the p21 activated", "the p21 activated protein kinase", "activated protein kinase pak", "protein kinase pak 2", "kinase pak 2 stimulates", "pak 2 stimulates a cell", "2 stimulates a cell death", "stimulates a cell death response", "a cell death response characterized", "cell death response characterized by", "death response characterized by increased", "response characterized by increased cell", "characterized by increased cell rounding", "by increased cell rounding and", "increased cell rounding and apoptotic", "cell rounding and apoptotic chromatin", "rounding and apoptotic chromatin condensation", "apoptotic chromatin condensation see", "chromatin condensation see jakobi", "condensation see jakobi et", "jakobi et al. 2003", "et al. 2003 .", "al. 2003 . pak", "2003 . pak 2 is", ". pak 2 is proteolytically", "pak 2 is proteolytically cleaved", "2 is proteolytically cleaved by", "is proteolytically cleaved by caspase", "proteolytically cleaved by caspase 3", "cleaved by caspase 3 producing", "by caspase 3 producing a", "caspase 3 producing a constitutively", "3 producing a constitutively active", "a constitutively active fragment", "active fragment pak", "pak 2p34. following cleavage", "following cleavage pak 2p34", "cleavage pak 2p34 is", "pak 2p34 is autophosphorylated at", "2p34 is autophosphorylated at thr", "is autophosphorylated at thr 402", "autophosphorylated at thr 402 and", "at thr 402 and transported", "thr 402 and transported to", "402 and transported to the", "and transported to the nucleus", "transported to the nucleus where", "to the nucleus where it", "the nucleus where it accumulates", "nucleus where it accumulates due", "where it accumulates due to", "it accumulates due to the", "accumulates due to the loss", "due to the loss of", "to the loss of its", "the loss of its nuclear", "loss of its nuclear export", "of its nuclear export signal", "its nuclear export signal motif", "export signal motif jakobi", "signal motif jakobi et", "motif jakobi et al.", "al. 2003 . the", "2003 . the activity of", ". the activity of pak", "the activity of pak 2p34", "activity of pak 2p34 appears", "of pak 2p34 appears to", "pak 2p34 appears to be", "2p34 appears to be regulated", "appears to be regulated both", "to be regulated both by", "be regulated both by proteosomal", "regulated both by proteosomal degradation", "by proteosomal degradation jakobi", "proteosomal degradation jakobi et", "degradation jakobi et al.", "al. 2003 and", "2003 and by", "and by association with", "by association with the gtpase", "association with the gtpase activating", "with the gtpase activating protein", "the gtpase activating protein ps", "gtpase activating protein ps gap/", "activating protein ps gap/ rhg", "protein ps gap/ rhg 10.", "ps gap/ rhg 10. this", "gap/ rhg 10. this interaction", "10. this interaction inhibits", "this interaction inhibits the", "interaction inhibits the kinase", "inhibits the kinase activity of", "kinase activity of pak", "of pak 2p34 and", "pak 2p34 and changes the", "2p34 and changes the localization", "and changes the localization of", "changes the localization of pak", "the localization of pak 2p34", "localization of pak 2p34 from", "of pak 2p34 from the", "pak 2p34 from the nucleus", "2p34 from the nucleus to", "from the nucleus to the", "the nucleus to the perinuclear", "nucleus to the perinuclear region", "the perinuclear region koeppel", "perinuclear region koeppel et", "region koeppel et al.", "koeppel et al. 2004", "2004 . pak 2p34", ". pak 2p34 may", "pak 2p34 may function", "may function in", "function in the down", "in the down regulation of", "the down regulation of translation", "down regulation of translation initiation", "regulation of translation initiation in", "of translation initiation in apoptosis", "translation initiation in apoptosis through", "initiation in apoptosis through phosphorylation", "in apoptosis through phosphorylation of", "apoptosis through phosphorylation of mnk1", "phosphorylation of mnk1 orton", "of mnk1 orton et", "mnk1 orton et al.", "orton et al. 2004 ." ] }, { "record_id": "GLY_000594_1_1610", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "211994", "r hsa", "hsa 211994", "r hsa 211994" ] }, { "record_id": "GLY_000594_1_1610", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sterols are", "are 12", "12 hydroxylated", "hydroxylated by", "by cyp8b1", "sterols are 12", "are 12 hydroxylated", "12 hydroxylated by", "hydroxylated by cyp8b1", "sterols are 12 hydroxylated", "are 12 hydroxylated by", "12 hydroxylated by cyp8b1", "sterols are 12 hydroxylated by", "are 12 hydroxylated by cyp8b1", "cytochrome p450", "p450 8b1", "sterol 12", "12 alpha", "has a", "a broad", "broad substrate", "substrate specificity", "specificity including", "including a", "a number", "number of", "of 7", "7 alpha", "hydroxylated c27", "c27 steroids.", "steroids. it", "it is", "is also", "also involved", "involved in", "in bile", "bile acid", "acid synthesis", "synthesis and", "and is", "is responsible", "responsible for", "for the", "the balance", "balance between", "between the", "the formation", "formation of", "of cholic", "cholic acid", "acid and", "and chenodeoxycholic", "chenodeoxycholic acid", "gafvels et", "et al.", "al. 1999", "1999 .", "cytochrome p450 8b1", "8b1 cyp8b1", "cyp8b1 sterol", "sterol 12 alpha", "alpha hydroxylase", "hydroxylase has", "has a broad", "a broad substrate", "broad substrate specificity", "substrate specificity including", "specificity including a", "including a number", "a number of", "number of 7", "of 7 alpha", "alpha hydroxylated", "hydroxylated c27 steroids.", "c27 steroids. it", "steroids. it is", "it is also", "is also involved", "also involved in", "involved in bile", "in bile acid", "bile acid synthesis", "acid synthesis and", "synthesis and is", "and is responsible", "is responsible for", "responsible for the", "for the balance", "the balance between", "balance between the", "between the formation", "the formation of", "formation of cholic", "of cholic acid", "cholic acid and", "acid and chenodeoxycholic", "and chenodeoxycholic acid", "acid gafvels", "gafvels et al.", "et al. 1999", "al. 1999 .", "p450 8b1 cyp8b1", "cyp8b1 sterol 12", "12 alpha hydroxylase", "hydroxylase has a", "has a broad substrate", "a broad substrate specificity", "broad substrate specificity including", "substrate specificity including a", "specificity including a number", "including a number of", "a number of 7", "number of 7 alpha", "7 alpha hydroxylated", "alpha hydroxylated c27", "hydroxylated c27 steroids. it", "c27 steroids. it is", "steroids. it is also", "it is also 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{ "record_id": "GLY_000594_1_1611", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "217271", "r hsa", "hsa 217271", "r hsa 217271" ] }, { "record_id": "GLY_000594_1_1611", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fmo oxidises", "oxidises nucleophiles", "fmo oxidises nucleophiles", "flavin containing", "containing monooxygenases", "are the", "the second", "second family", "family of", "of microsomal", "microsomal oxidative", "oxidative enzymes", "enzymes with", "with broad", "broad and", "and overlapping", "overlapping specificity.", "specificity. the", "the major", "major reactions", "reactions fmos", "fmos catalyze", "catalyze are", "are nucleophilic", "nucleophilic hetero", "hetero atom", "atom compounds", "compounds such", "such as", "as nitrogen", "sulfur or", "or phosphorus", "phosphorus as", "as the", "the hetero", "atom to", "to form", "form n", "n oxides", "s oxides", "oxides or", "or p", "p oxides", "oxides respectively.", "respectively. despite", "despite the", "the functional", "functional overlap", "overlap with", "with cytochrome", "cytochrome p450s", "the mechanism", "mechanism of", "of action", "action differs.", "differs. fmos", "fmos bind", "bind and", "and activate", "activate molecular", "molecular oxygen", "oxygen before", "before the", "the substrate", "substrate binds", "binds to", "to the", "the enzyme", "picture .", ". they", "they also", "also require", "require flavin", "flavin adenosine", "adenosine dinucleotide", "as a", "a cofactor.", "cofactor. unlike", "unlike cytochrome", "cytochrome p450", "p450 enzymes", "fmos are", "are heat", "heat labile", "a useful", "useful way", "way to", "to distinguish", "distinguish which", "which enzyme", "enzyme system", "system is", "is at", "at work", "work for", "for researchers", "researchers studying", "studying metabolism.", "metabolism. also", "are not", "not inducible", "inducible by", "by 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fmos", "the major reactions fmos catalyze", "major reactions fmos catalyze are", "reactions fmos catalyze are nucleophilic", "fmos catalyze are nucleophilic hetero", "catalyze are nucleophilic hetero atom", "are nucleophilic hetero atom compounds", "nucleophilic hetero atom compounds such", "hetero atom compounds such as", "atom compounds such as nitrogen", "such as nitrogen sulfur", "as nitrogen sulfur or", "nitrogen sulfur or phosphorus", "sulfur or phosphorus as the", "or phosphorus as the hetero", "phosphorus as the hetero atom", "as the hetero atom to", "the hetero atom to form", "hetero atom to form n", "atom to form n oxides", "form n oxides s", "n oxides s oxides", "oxides s oxides or", "s oxides or p oxides", "oxides or p oxides respectively.", "or p oxides respectively. despite", "p oxides respectively. despite the", "oxides respectively. despite the functional", "respectively. despite the functional overlap", "despite the functional overlap with", "the functional overlap with cytochrome", "functional overlap with cytochrome p450s", "with cytochrome p450s the", "cytochrome p450s the mechanism", "p450s the mechanism of", "the mechanism of action differs.", "mechanism of action differs. fmos", "of action differs. fmos bind", "action differs. fmos bind and", "differs. fmos bind and activate", "fmos bind and activate molecular", "bind and activate molecular oxygen", "and activate molecular oxygen before", "activate molecular oxygen before the", "molecular oxygen before the substrate", "oxygen before the substrate binds", "before the substrate binds to", "the substrate binds to the", "substrate binds to the enzyme", "to the enzyme picture", "the enzyme picture .", "enzyme picture . they", "picture . they also require", ". they also require flavin", "they also require flavin adenosine", "also require flavin adenosine dinucleotide", "flavin adenosine dinucleotide fad", "dinucleotide fad as", "fad as a cofactor.", "as a cofactor. unlike cytochrome", "a cofactor. unlike cytochrome p450", "cofactor. unlike cytochrome p450 enzymes", "cytochrome p450 enzymes fmos", "p450 enzymes fmos are", "enzymes fmos are heat", "are heat labile a", "heat labile a useful", "labile a useful way", "a useful way to distinguish", "useful way to distinguish which", "way to distinguish which enzyme", "to distinguish which enzyme system", "distinguish which enzyme system is", "which enzyme system is at", "enzyme system is at work", "system is at work for", "is at work for researchers", "at work for researchers studying", "work for researchers studying metabolism.", "for researchers studying metabolism. also", "studying metabolism. also fmos", "metabolism. also fmos are", "also fmos are not", "fmos are not inducible by", "are not inducible by substrates", "inducible by substrates unlike", "by substrates unlike the", "substrates unlike the p450", "unlike the p450 enzymes.\\n", "the p450 enzymes.\\n 1", "p450 enzymes.\\n 1 ", "enzymes.\\n 1 nadph", "color=red> 1 nadph binds", "1 nadph binds to", " nadph binds to the", "nadph binds to the enzyme", "binds to the enzyme and", "to the enzyme and reduces", "the enzyme and reduces the", "enzyme and reduces the prosthetic", "and reduces the prosthetic group", "reduces the prosthetic group fad", "the prosthetic group fad to", "prosthetic group fad to fadh2.", "group fad to fadh2. nadp+", "fad to fadh2. nadp+ remains", "to fadh2. nadp+ remains bound", "fadh2. nadp+ remains bound to", "nadp+ remains bound to the", "remains bound to the enzyme.\\n", "to the enzyme.\\n 2", "the enzyme.\\n 2 ", "enzyme.\\n 2 incorporation", "color=red> 2 incorporation of", "2 incorporation of molecular", " incorporation of molecular oxygen", "incorporation of molecular oxygen to", "of molecular oxygen to form", "molecular oxygen to form a", "oxygen to form a hydroperoxide.\\n", "form a hydroperoxide.\\n 3", "a hydroperoxide.\\n 3 ", "hydroperoxide.\\n 3 a", "color=red> 3 a peroxide", "3 a peroxide oxygen", " a peroxide oxygen is", "a peroxide oxygen is transferred", "peroxide oxygen is transferred to", "oxygen is transferred to the", "is transferred to the substrate.\\n", "to the substrate.\\n 4", "the substrate.\\n 4 ", "substrate.\\n 4 water", "color=red> 4 water is", "4 water is released.\\n water is released.\\n", "water is released.\\n 5", "is released.\\n 5 ", "released.\\n 5 nadp+", "color=red> 5 nadp+ dissociates", "5 nadp+ dissociates returning", " nadp+ dissociates returning the", "nadp+ dissociates returning the enzyme", "dissociates returning the enzyme to", "returning the enzyme to its", "the enzyme to its initial", "enzyme to its initial state.\\n\\nto", "to its initial state.\\n\\nto date", "initial state.\\n\\nto date there", "state.\\n\\nto date there are", "date there are 6", "there are 6 isozymes of", "are 6 isozymes of fmo", "isozymes of fmo fmo1", "of fmo fmo1 6", "fmo1 6 in humans", "in humans the most", "humans the most prominent", "the most prominent and active", "most prominent and active one", "prominent and active one being", "and active one being fmo3.", "active one being fmo3. the", "one being fmo3. the fmo6", "being fmo3. the fmo6 gene", "fmo3. the fmo6 gene does", "the fmo6 gene does not", "fmo6 gene does not encode", "gene does not encode for", "does not encode for a", "not encode for a functional", "encode for a functional enzyme", "for a functional enzyme although", "a functional enzyme although it", "functional enzyme although it has", "enzyme although it has the", "although it has the greatest", "it has the greatest sequence", "has the greatest sequence similarity", "the greatest sequence similarity with", "greatest sequence similarity with fmo3", "similarity with fmo3 71%", "71% whilst the", "whilst the others range from", "the others range from 50", "others range from 50 58%", "range from 50 58% sequence", "from 50 58% sequence similarity", "50 58% sequence similarity with", "58% sequence similarity with fmo3.", "sequence similarity with fmo3. fmo1", "similarity with fmo3. fmo1 3", "with fmo3. fmo1 3 are", "fmo3. fmo1 3 are the", "fmo1 3 are the ones", "3 are the ones that", "are the ones that exhibit", "the ones that exhibit activity", "ones that exhibit activity towards", "that exhibit activity towards nucleophiles", "activity towards nucleophiles the", "towards nucleophiles the others", "nucleophiles the others are", "the others are insignificant in", "others are insignificant in this", "are insignificant in this respect", "in this respect cashman", "this respect cashman 2003", "cashman 2003 krueger &", "2003 krueger & williams", "krueger & williams 2005 ." ] }, { "record_id": "GLY_000594_1_1612", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206280", "r hsa", "hsa 2206280", "r hsa 2206280" ] }, { "record_id": "GLY_000594_1_1612", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps ix", "natowicz syndrome", "ix natowicz", "mps ix natowicz", "ix natowicz syndrome", "mucopolysaccharidosis type", "type ix", "hyaluronidase deficiency", "is a", "a rare", "rare lysosomal", "lysosomal storage", "storage disease", "disease characterized", "characterized by", "by high", "high hyaluronan", "concentration in", "in the", "the serum", "serum resulting", "resulting from", "from deficiency", "deficiency in", "in hyaluronidase", "hyaluronidase 1", "which normally", "normally hydrolyses", "hydrolyses 1", "1 4", "4 linkages", "linkages between", "between n", "n acetylglucosamine", "and d", "d glucuronate", "residues. symptoms", "symptoms of", "of mps", "ix are", "are periodically", "periodically painful", "painful soft", "soft tissue", "tissue masses", "masses around", "around the", "the joints", "acquired short", "short stature", "stature and", "and erosion", "erosion of", "of the", "the hip", "hip joint", "although joint", "joint movement", "movement and", "and intelligence", "intelligence are", "are normal", "natowicz et", "et al.", "al. 1996", "triggs raine", "raine et", "al. 1999", "1999 .", "mucopolysaccharidosis type ix", "ix mps", "syndrome hyaluronidase", "deficiency mim:601492", "mim:601492 is", "601492 is", "is a rare", "a rare lysosomal", "rare lysosomal storage", "lysosomal storage disease", "storage disease characterized", "disease characterized by", "characterized by high", "by high hyaluronan", "hyaluronan ha", "ha concentration", "concentration in the", "in the serum", "the serum resulting", "serum resulting from", "resulting from deficiency", "from deficiency in", "deficiency in hyaluronidase", "in hyaluronidase 1", "1 hyal1", "hyal1 mim:607071", "mim:607071 which", "607071 which", "which normally hydrolyses", "normally hydrolyses 1", "hydrolyses 1 4", "1 4 linkages", "4 linkages between", "linkages between n", "between n acetylglucosamine", "acetylglucosamine glcnac", "glcnac and", "and d glucuronate", "glucuronate glca", "glca residues.", "residues. symptoms of", 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joints", "the joints acquired", "joints acquired short", "acquired short stature and", "short stature and erosion", "stature and erosion of", "and erosion of the", "erosion of the hip", "of the hip joint", "hip joint although", "joint although joint", "although joint movement and", "joint movement and intelligence", "movement and intelligence are", "and intelligence are normal", "are normal natowicz", "normal natowicz et", "natowicz et al. 1996", "al. 1996 triggs", "1996 triggs raine", "triggs raine et al.", "raine et al. 1999", "et al. 1999 .", "mucopolysaccharidosis type ix mps", "type ix mps ix", "mps ix natowicz syndrome", "natowicz syndrome hyaluronidase deficiency", "deficiency mim:601492 is", "mim:601492 is a rare", "601492 is a rare", "is a rare lysosomal storage", "a rare lysosomal storage disease", "rare lysosomal storage disease characterized", "lysosomal storage disease characterized by", "storage disease characterized by high", "disease characterized by high hyaluronan", 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painful soft tissue", "periodically painful soft tissue masses", "painful soft tissue masses around", "soft tissue masses around the", "tissue masses around the joints", "around the joints acquired", "the joints acquired short", "joints acquired short stature", "acquired short stature and erosion", "short stature and erosion of", "stature and erosion of the", "and erosion of the hip", "erosion of the hip joint", "the hip joint although", "hip joint although joint", "joint although joint movement", "although joint movement and intelligence", "joint movement and intelligence are", "movement and intelligence are normal", "intelligence are normal natowicz", "are normal natowicz et", "normal natowicz et al.", "et al. 1996 triggs", "al. 1996 triggs raine", "1996 triggs raine et", "triggs raine et al. 1999", "raine et al. 1999 ." ] }, { "record_id": "GLY_000594_1_1613", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206282", "r hsa", "hsa 2206282", "r hsa 2206282" ] }, { "record_id": "GLY_000594_1_1613", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps iiib", "sanfilippo syndrome", "syndrome b", "sanfilippo syndrome b", "iiib sanfilippo", "mps iiib sanfilippo", "iiib sanfilippo syndrome", "mucopolysaccharidosis iii", "was described", "described in", "in 1963", "1963 by", "by a", "a pediatrician", "pediatrician named", "named sylvester", "sylvester sanfilippo", "j. pediat.", "pediat. 63:", "63: 837838", "no reference", "reference .", ". mps", "mucopolysaccharidosis type", "type iiib", "syndrome type", "type b", "is an", "an autosomal", "autosomal recessive", "recessive genetic", "genetic disorder", "disorder due", "due to", "to loss", "loss of", "of function", "function of", "of alpha", "alpha n", "n acetylglucosaminidase", "involved in", "in the", "the hydrolysis", "hydrolysis of", "of terminal", "terminal non", "non reducing", "reducing n", "n acetylglucosamine", 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sanfilippo j. pediat.", "sanfilippo j. pediat. 63:", "pediat. 63: 837838 1963", "837838 1963 no", "1963 no reference .", "no reference . mps iiib", ". mps iiib mucopolysaccharidosis", "mps iiib mucopolysaccharidosis type", "iiib mucopolysaccharidosis type iiib", "mucopolysaccharidosis type iiib mps", "type iiib mps iiib", "mps iiib sanfilippo syndrome", "iiib sanfilippo syndrome type", "syndrome type b mim:252920", "b mim:252920 is", "mim:252920 is an autosomal", "252920 is an autosomal", "is an autosomal recessive genetic", "an autosomal recessive genetic disorder", "autosomal recessive genetic disorder due", "recessive genetic disorder due to", "genetic disorder due to loss", "disorder due to loss of", "due to loss of function", "to loss of function of", "loss of function of alpha", "of function of alpha n", "function of alpha n acetylglucosaminidase", "alpha n acetylglucosaminidase naglu", "acetylglucosaminidase naglu mim:609701", "mim:609701 involved in", "609701 involved in", 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sulfate", "of keratan sulfate ks", "ks matalon et", "matalon et al. 1974 .", "et al. 1974 . the", "al. 1974 . the result", "1974 . the result is", ". the result is accumulation", "the result is accumulation of", "result is accumulation of ks/ds", "is accumulation of ks/ds in", "accumulation of ks/ds in cells", "of ks/ds in cells and", "ks/ds in cells and overexcretion", "in cells and overexcretion in", "cells and overexcretion in urine.", "and overexcretion in urine. severe", "overexcretion in urine. severe osteochondrodysplasia", "in urine. severe osteochondrodysplasia is", "urine. severe osteochondrodysplasia is a", "severe osteochondrodysplasia is a commonly", "osteochondrodysplasia is a commonly seen", "is a commonly seen phenotype", "a commonly seen phenotype for", "commonly seen phenotype for this", "seen phenotype for this disease.", "phenotype for this disease. the", "for this disease. the severity", "this disease. the severity of", "disease. the severity of the", "the severity 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"GLY_000594_1_1615", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps iiic", "sanfilippo syndrome", "syndrome c", "sanfilippo syndrome c", "iiic sanfilippo", "mps iiic sanfilippo", "iiic sanfilippo syndrome", "mucopolysaccharidosis iii", "was described", "described in", "in 1963", "1963 by", "by a", "a pediatrician", "pediatrician named", "named sylvester", "sylvester sanfilippo", "j. pediat.", "pediat. 63:", "63: 837838", "no reference", "reference .", ". mucopolysaccharidosis", "mucopolysaccharidosis type", "type iiic", "is an", "an autosomal", "autosomal recessive", "recessive genetic", "genetic disorder", "disorder due", "due to", "to the", "the loss", "loss of", "of heparan", "heparan alpha", "alpha glucosaminide", "glucosaminide n", "n acetyltransferase", "that normally", "normally acetylates", "acetylates the", "the non", "non reducing", "reducing terminal", "terminal alpha", "alpha glucosamine", "glucosamine residue", "residue of", "heparan sulfate.", "sulfate. the", "the molecular", "molecular defects", "defects underlying", "underlying mps", "iiic remained", "remained unknown", "unknown for", "for almost", "almost three", "three decades", "decades due", "the low", "low tissue", "tissue content", "content and", "and instability", "instability of", "of hgsnat.", "hgsnat. but", "during the", "the last", "last decade", "the gene", "gene was", "was cloned", "cloned in", "in parallel", "parallel by", "by two", "two different", "different groups", "groups and", "and shown", "shown to", "to contain", "contain 18", "18 exons", "exons and", "and span", "span approximately", "approximately 62kb", "fan et", "et al.", "al. 2006", "hrebicek et", "2006 .", ". loss", "of hgsnat", "hgsnat results", "results in", "in build", "build up", "up of", "of this", "this glycosaminglycan", "in cells", "cells and", "and tissues", "tissues and", "and is", "is characterized", "characterized by", "by severe", "severe central", "central nervous", "nervous system", "system degeneration", "degeneration but", "but only", "only with", "with mild", "mild somatic", "somatic disease", "disease and", "and death", "death occurs", "occurs typically", "typically during", "the second", "second or", "or third", "third decade", "decade of", "of life", "kresse et", "al. 1978", "klein et", "feldhammer et", "al. 2009", "de ruijter", "ruijter et", "al. 2011", "2011 .", "iii sanfilippo", "syndrome was", "was described in", "described in 1963", "in 1963 by", "1963 by a", "by a pediatrician", "a pediatrician named", "pediatrician named sylvester", "named sylvester sanfilippo", "sanfilippo j.", "j. pediat. 63:", "pediat. 63: 837838", "837838 1963", "1963 no", "no reference .", "reference . mucopolysaccharidosis", ". mucopolysaccharidosis type", "mucopolysaccharidosis type iiic", "iiic mps", "c mim:252930", "mim:252930 is", "252930 is", "is an autosomal", "an autosomal recessive", "autosomal recessive genetic", "recessive genetic disorder", 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pediat. 63: 837838", "63: 837838 1963", "1963 no reference", "no reference . mucopolysaccharidosis", "reference . mucopolysaccharidosis type", ". mucopolysaccharidosis type iiic", "type iiic mps", "iiic mps iiic", "syndrome c mim:252930", "mim:252930 is an", "252930 is an", "is an autosomal recessive", "an autosomal recessive genetic", "autosomal recessive genetic disorder", "recessive genetic disorder due", "genetic disorder due to", "disorder due to the", "due to the loss", "to the loss of", "the loss of heparan", "loss of heparan alpha", "of heparan alpha glucosaminide", "heparan alpha glucosaminide n", "alpha glucosaminide n acetyltransferase", "n acetyltransferase hgsnat", "mim:610453 that normally", "610453 that normally", "that normally acetylates the", "normally acetylates the non", "acetylates the non reducing", "the non reducing terminal", "non reducing terminal alpha", "reducing terminal alpha glucosamine", "terminal alpha glucosamine residue", "alpha glucosamine residue 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"different groups and shown", "groups and shown to", "and shown to contain", "shown to contain 18", "to contain 18 exons", "contain 18 exons and", "18 exons and span", "exons and span approximately", "and span approximately 62kb", "approximately 62kb fan", "62kb fan et", "fan et al. 2006", "al. 2006 hrebicek", "2006 hrebicek et", "hrebicek et al. 2006", "et al. 2006 .", "al. 2006 . loss", "2006 . loss of", ". loss of hgsnat", "loss of hgsnat results", "of hgsnat results in", "hgsnat results in build", "results in build up", "in build up of", "build up of this", "up of this glycosaminglycan", "this glycosaminglycan gag", "gag in cells", "in cells and tissues", "cells and tissues and", "and tissues and is", "tissues and is characterized", "and is characterized by", "is characterized by severe", "characterized by severe central", "by severe central nervous", "severe central nervous system", "central nervous system degeneration", "nervous system degeneration but", "system degeneration but 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pediatrician named sylvester sanfilippo", "named sylvester sanfilippo j.", "sylvester sanfilippo j. pediat.", "sanfilippo j. pediat. 63:", "pediat. 63: 837838 1963", "837838 1963 no", "1963 no reference .", "no reference . mucopolysaccharidosis type", "reference . mucopolysaccharidosis type iiic", "mucopolysaccharidosis type iiic mps", "type iiic mps iiic", "mps iiic sanfilippo syndrome", "iiic sanfilippo syndrome c", "sanfilippo syndrome c mim:252930", "c mim:252930 is", "mim:252930 is an autosomal", "252930 is an autosomal", "is an autosomal recessive genetic", "an autosomal recessive genetic disorder", "autosomal recessive genetic disorder due", "recessive genetic disorder due to", "genetic disorder due to the", "disorder due to the loss", "due to the loss of", "to the loss of heparan", "the loss of heparan alpha", "loss of heparan alpha glucosaminide", "of heparan alpha glucosaminide n", "heparan alpha glucosaminide n acetyltransferase", "glucosaminide n acetyltransferase hgsnat", "acetyltransferase hgsnat mim:610453", "hgsnat mim:610453 that", "mim:610453 that normally acetylates", "610453 that normally acetylates", "that normally acetylates the non", "normally acetylates the non reducing", "acetylates the non reducing terminal", "the non reducing terminal alpha", "non reducing terminal alpha glucosamine", "reducing terminal alpha glucosamine residue", "terminal alpha glucosamine residue of", "glucosamine residue of heparan", "residue of heparan sulfate.", "of heparan sulfate. the", "heparan sulfate. the molecular defects", "sulfate. the molecular defects underlying", "the molecular defects underlying mps", "molecular defects underlying mps iiic", "defects underlying mps iiic remained", "underlying mps iiic remained unknown", "mps iiic remained unknown for", "iiic remained unknown for almost", "remained unknown for almost three", "unknown for almost three decades", "for almost three decades due", "almost three decades due to", "three decades due to the", "decades due to the low", "due to the low tissue", "to the low tissue content", "the low tissue content and", "low tissue content and instability", "tissue content and instability of", "content and instability of hgsnat.", "and instability of hgsnat. but", "of hgsnat. but during", "hgsnat. but during the", "but during the last", "the last decade the", "last decade the gene", "decade the gene was", "the gene was cloned in", "gene was cloned in parallel", "was cloned in parallel by", "cloned in parallel by two", "in parallel by two different", "parallel by two different groups", "by two different groups and", "two different groups and shown", "different groups and shown to", "groups and shown to contain", "and shown to contain 18", "shown to contain 18 exons", "to contain 18 exons and", "contain 18 exons and span", "18 exons and span approximately", "exons and span approximately 62kb", "span approximately 62kb fan", "approximately 62kb fan et", "62kb fan et al.", "et al. 2006 hrebicek", "al. 2006 hrebicek et", "2006 hrebicek et al.", "hrebicek et al. 2006 .", "et al. 2006 . loss", "al. 2006 . loss of", "2006 . loss of hgsnat", ". loss of hgsnat results", "loss of hgsnat results in", "of hgsnat results in build", "hgsnat results in build up", "results in build up of", "in build up of this", "build up of this glycosaminglycan", "of this glycosaminglycan gag", "glycosaminglycan gag in", "gag in cells and", "in cells and tissues and", "cells and tissues and is", "and tissues and is characterized", "tissues and is characterized by", "and is characterized by severe", "is characterized by severe central", "characterized by severe central nervous", "by severe central nervous system", "severe central nervous system degeneration", "central nervous system degeneration but", "nervous system degeneration but only", "system degeneration but only with", "degeneration but only with mild", "but only with mild somatic", "only with mild somatic disease", "with mild somatic disease and", "mild somatic disease and death", "somatic disease and death occurs", "disease and death occurs typically", "and death occurs typically during", "death occurs typically during the", "occurs typically during the second", "typically during the second or", "during the second or third", "the second or third decade", "second or third decade of", "or third decade of life", "decade of life kresse", "of life kresse et", "life kresse et al.", "et al. 1978 klein", "al. 1978 klein et", "1978 klein et al.", "et al. 1978 feldhammer", "al. 1978 feldhammer et", "1978 feldhammer et al.", "et al. 2009 de", "al. 2009 de ruijter", "2009 de ruijter et", "de ruijter et al. 2011", "ruijter et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1616", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206302", "r hsa", "hsa 2206302", "r hsa 2206302" ] }, { "record_id": "GLY_000594_1_1616", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps i", "hurler syndrome", "i hurler", "mps i hurler", "i hurler syndrome", "mucopolysaccharidosis type", "type i", "hurler's disease", "hirler scheie", "scheie syndrome", "607015 and", "and 607016", "is an", "an autosomal", "autosomal recessive", "recessive genetic", "genetic disorder", "disorder where", "where there", "there is", "is a", "a deficiency", "deficiency of", "of alpha", "alpha l", "l iduronidase", "a glycosidase", "glycosidase that", "that removes", "removes non", "non reducing", "reducing terminal", "terminal alpha", "l iduronide", "iduronide residues", "residues during", "during the", "the lysosomal", "lysosomal degradation", "degradation of", "of the", "the glycosaminoglycans", "glycosaminoglycans heparan", "heparan sulphate", "sulphate and", "and dermatan", "dermatan sulphate", "mckusick 1959", "1959 .", ". in", "in 1992", "scott and", "and colleagues", "colleagues were", "were able", "able to", "to clone", "clone and", "and purify", "purify the", "the gene", "gene that", "that encodes", "encodes this", "this enzyme", "demonstrating that", "that it", "it spans", "spans approximately", "approximately 19", "19 kb", "kb and", "and contains", "contains 14", "14 exons", "scott et", "et al.", "al. 1992", "1992 .
              hurler", ".
              hurler syndrome", "syndrome is", "is named", "named after", "after a", "a german", "german paediatrician", "paediatrician gertrud", "gertrud hurler", "no reference", "reference available", "available .", ". the", "the result", "result is", "is build", "build up", "up of", "of heparan", "heparan sulfate", "sulfate and", "dermatan sulfate", "sulfate in", "in the", "the body", "body and", "and increased", "increased urinary", "urinary excretion", "excretion of", "of these", "these gags.", "gags. symptoms", "symptoms and", "and signs", "signs include", "include hepatosplenomegaly", "unique facial", "facial features", "corneal clouding", "progressive mental", "mental retardation", "retardation appears", "appears during", "during childhood", "childhood and", "and early", "early death", "death can", "can occur", "occur due", "due to", "to organ", "organ damage", "campos &", "& monaga", "monaga 2012", "2012 .", ". mps", "i is", "is divided", "divided into", "into three", "three subtypes", "ranging from", "from severe", "severe to", "to mild", "mild phenotypes", "type ih", "type ih/s", "hurlerscheie syndrome", "mim: 607015", " 607015", "and mucopolysaccharidosis", "type is", "mim: 607016", " 607016", "mckusick 1972", "1972 .", "mucopolysaccharidosis type i", "i mps", "syndrome hurler's", "disease gargoylism", "gargoylism scheie", "scheie hirler", "hirler scheie syndrome", "mim:607014 607015", "607014 607015", "607015 and 607016", "607016 is", "is an autosomal", "an autosomal recessive", "autosomal recessive genetic", "recessive genetic disorder", "genetic disorder where", "disorder where there", "where there is", "there is a", "is a deficiency", "a deficiency of", "deficiency of alpha", "of alpha l", "alpha l iduronidase", "iduronidase idua", "idua mim:252800", "a glycosidase that", "glycosidase that removes", "that removes non", "removes non reducing", "non reducing terminal", "reducing terminal alpha", "terminal alpha l", "alpha l iduronide", "l iduronide residues", "iduronide residues during", "residues during the", "during the lysosomal", "the lysosomal degradation", "lysosomal degradation of", "degradation of the", "of the glycosaminoglycans", "the glycosaminoglycans heparan", "glycosaminoglycans heparan sulphate", "heparan sulphate and", "sulphate and dermatan", "and dermatan sulphate", "sulphate mckusick", "mckusick 1959 .", "1959 . in", ". in 1992", "1992 scott", "scott and colleagues", "and colleagues were", "colleagues were able", "were able to", "able to clone", "to clone and", "clone and purify", "and purify the", "purify the gene", "the gene that", "gene that encodes", "that encodes this", "encodes this enzyme", "enzyme idua", "idua demonstrating", "demonstrating that it", "that it spans", "it spans approximately", "spans approximately 19", "approximately 19 kb", "19 kb and", "kb and contains", "and contains 14", "contains 14 exons", "exons scott", "scott et al.", "et al. 1992", "al. 1992 .
              hurler", "1992 .
              hurler syndrome", ".
              hurler syndrome is", "syndrome is named", "is named after", "named after a", "after a german", "a german paediatrician", "german paediatrician gertrud", "paediatrician gertrud hurler", "hurler 1919", "1919 no", "no reference available", "reference available .", "available . the", ". the result", "the result is", "result is build", "is build up", "build up of", "up of heparan", "of heparan sulfate", "heparan sulfate and", "sulfate and dermatan", "and dermatan sulfate", "dermatan sulfate in", "sulfate in the", "in the body", "the body and", "body and increased", "and increased urinary", "increased urinary excretion", "urinary excretion of", "excretion of these", "of these gags.", "these gags. symptoms", "gags. symptoms and", "symptoms and signs", "and signs include", "signs include hepatosplenomegaly", "hepatosplenomegaly dwarfism", "dwarfism unique", "unique facial features", "features corneal", "clouding retinopathy", "retinopathy progressive", "progressive mental retardation", "mental retardation appears", "retardation appears during", "appears during childhood", "during childhood and", "childhood and early", "and early death", "early death can", "death can occur", "can occur due", "occur due to", "due to organ", "to organ damage", "damage campos", "campos & monaga", "& monaga 2012", "monaga 2012 .", "2012 . mps", ". mps i", "mps i is", "i is divided", "is divided into", "divided into three", "into three subtypes", "subtypes ranging", "ranging from severe", "from severe to", "severe to mild", "to mild phenotypes", "phenotypes mucopolysaccharidosis", "mucopolysaccharidosis type ih", "ih mpsih", "mpsih hurler", "syndrome mim:607014", "mucopolysaccharidosis type ih/s", "ih/s mpsih/s", "mpsih/s hurlerscheie", "syndrome mim:", "and mucopolysaccharidosis type", "mucopolysaccharidosis type is", "is mpsis", "mpsis scheie", "607016 respectively", "respectively mckusick", "mckusick 1972 .", "type i mps", "i mps i", "hurler syndrome hurler's", "syndrome hurler's disease", "hurler's disease gargoylism", "scheie hirler scheie", "mim:607014 607015 and", "607014 607015 and", "and 607016 is", "607016 is an", "is an autosomal recessive", "an autosomal recessive genetic", "autosomal recessive genetic disorder", "recessive genetic disorder where", "genetic disorder where there", "disorder where there is", "where there is a", "there is a deficiency", "is a deficiency of", "a deficiency of alpha", "deficiency of alpha l", "of alpha l iduronidase", "l iduronidase idua", "mim:252800 a", "252800 a", "a glycosidase that removes", "glycosidase that removes non", "that removes non reducing", "removes non reducing terminal", "non reducing terminal alpha", "reducing terminal alpha l", "terminal alpha l iduronide", "alpha l iduronide residues", "l iduronide residues during", "iduronide residues during the", "residues during the lysosomal", "during the lysosomal degradation", "the lysosomal degradation of", "lysosomal degradation of the", "degradation of the glycosaminoglycans", "of the glycosaminoglycans heparan", "the glycosaminoglycans heparan sulphate", "glycosaminoglycans heparan sulphate and", "heparan sulphate and dermatan", "sulphate and dermatan sulphate", "dermatan sulphate mckusick", "sulphate mckusick 1959", "mckusick 1959 . in", "1959 . in 1992", "in 1992 scott", "1992 scott and", "scott and colleagues were", "and colleagues were able", "colleagues were able to", "were able to clone", "able to clone and", "to clone and purify", "clone and purify the", "and purify the gene", "purify the gene that", "the gene that encodes", "gene that encodes this", "that encodes this enzyme", "this enzyme idua", "idua demonstrating that", "demonstrating that it spans", "that it spans approximately", "it spans approximately 19", "spans approximately 19 kb", "approximately 19 kb and", "19 kb and contains", "kb and contains 14", "and contains 14 exons", "14 exons scott", "exons scott et", "scott et al. 1992", "et al. 1992 .
              hurler", "al. 1992 .
              hurler syndrome", "1992 .
              hurler syndrome is", ".
              hurler syndrome is named", "syndrome is named after", "is named after a", "named after a german", "after a german paediatrician", "a german paediatrician gertrud", "german paediatrician gertrud hurler", "gertrud hurler 1919", "1919 no reference", "no reference available .", "reference available . the", "available . the result", ". the result is", "the result is build", "result is build up", "is build up of", "build up of heparan", "up of heparan sulfate", "of heparan sulfate and", "heparan sulfate and dermatan", "sulfate and dermatan sulfate", "and dermatan sulfate in", "dermatan sulfate in the", "sulfate in the body", "in the body and", "the body and increased", "body and increased urinary", "and increased urinary excretion", "increased urinary excretion of", "urinary excretion of these", "excretion of these gags.", "of these gags. symptoms", "these gags. symptoms and", "gags. symptoms and signs", "symptoms and signs include", "and signs include hepatosplenomegaly", "include hepatosplenomegaly dwarfism", "dwarfism unique facial", "facial features corneal", "features corneal clouding", "corneal clouding retinopathy", "retinopathy progressive mental", "progressive mental retardation appears", "mental retardation appears during", "retardation appears during childhood", "appears during childhood and", "during childhood and early", "childhood and early death", "and early death can", "early death can occur", "death can occur due", "can occur due to", "occur due to organ", "due to organ damage", "organ damage campos", "damage campos &", "campos & monaga 2012", "& monaga 2012 .", "monaga 2012 . mps", "2012 . mps i", ". mps i is", "mps i is divided", "i is divided into", "is divided into three", "divided into three subtypes", "three subtypes ranging", "subtypes ranging from", "ranging from severe to", "from severe to mild", "severe to mild phenotypes", "mild phenotypes mucopolysaccharidosis", "phenotypes mucopolysaccharidosis type", "type ih mpsih", "mpsih hurler syndrome", "hurler syndrome mim:607014", "mim:607014 mucopolysaccharidosis", "607014 mucopolysaccharidosis", "type ih/s mpsih/s", "mpsih/s hurlerscheie syndrome", "hurlerscheie syndrome mim:", "syndrome mim: 607015", "mim: 607015 and", " 607015 and", "607015 and mucopolysaccharidosis", "and mucopolysaccharidosis type is", "type is mpsis", "mpsis scheie syndrome", "scheie syndrome mim:", "syndrome mim: 607016", "mim: 607016 respectively", " 607016 respectively", "respectively mckusick 1972", "mucopolysaccharidosis type i mps", "type i mps i", "mps i hurler syndrome", "hurler syndrome hurler's disease", "disease gargoylism scheie", "gargoylism scheie hirler", "scheie hirler scheie syndrome", "scheie syndrome mim:607014", "mim:607014 607015 and 607016", "607014 607015 and 607016", "607015 and 607016 is", "and 607016 is an", "607016 is an autosomal", "is an autosomal recessive genetic", "an autosomal recessive genetic disorder", "autosomal recessive genetic disorder where", "recessive genetic disorder where there", "genetic disorder where there is", "disorder where there is a", "where there is a deficiency", "there is a deficiency of", "is a deficiency of alpha", "a deficiency of alpha l", "deficiency of alpha l iduronidase", "alpha l iduronidase idua", "iduronidase idua mim:252800", "mim:252800 a glycosidase", "252800 a glycosidase", "a glycosidase that removes non", "glycosidase that removes non reducing", "that removes non reducing terminal", "removes non reducing terminal alpha", "non reducing terminal alpha l", "reducing terminal alpha l iduronide", "terminal alpha l iduronide residues", "alpha l iduronide residues during", "l iduronide residues during the", "iduronide residues during the lysosomal", "residues during the lysosomal degradation", "during the lysosomal degradation of", "the lysosomal degradation of the", "lysosomal degradation of the glycosaminoglycans", "degradation of the glycosaminoglycans heparan", "of the glycosaminoglycans heparan sulphate", "the glycosaminoglycans heparan sulphate and", "glycosaminoglycans heparan sulphate and dermatan", "heparan sulphate and dermatan sulphate", "and dermatan sulphate mckusick", "dermatan sulphate mckusick 1959", "sulphate mckusick 1959 .", "mckusick 1959 . in 1992", ". in 1992 scott", "in 1992 scott and", "1992 scott and colleagues", "scott and colleagues were able", "and colleagues were able to", "colleagues were able to clone", "were able to clone and", "able to clone and purify", "to clone and purify the", "clone and purify the gene", "and purify the gene that", "purify the gene that encodes", "the gene that encodes this", "gene that encodes this enzyme", "encodes this enzyme idua", "enzyme idua demonstrating", "idua demonstrating that it", "demonstrating that it spans approximately", "that it spans approximately 19", "it spans approximately 19 kb", "spans approximately 19 kb and", "approximately 19 kb and contains", "19 kb and contains 14", "kb and contains 14 exons", "contains 14 exons scott", "14 exons scott et", "exons scott et al.", "scott et al. 1992 .
              hurler", "et al. 1992 .
              hurler syndrome", "al. 1992 .
              hurler syndrome is", "1992 .
              hurler syndrome is named", ".
              hurler syndrome is named after", "syndrome is named after a", "is named after a german", "named after a german paediatrician", "after a german paediatrician gertrud", "a german paediatrician gertrud hurler", "paediatrician gertrud hurler 1919", "hurler 1919 no", "1919 no reference available", "no reference available . the", "reference available . the result", "available . the result is", ". the result is build", "the result is build up", "result is build up of", "is build up of heparan", "build up of heparan sulfate", "up of heparan sulfate and", "of heparan sulfate and dermatan", "heparan sulfate and dermatan sulfate", "sulfate and dermatan sulfate in", "and dermatan sulfate in the", "dermatan sulfate in the body", "sulfate in the body and", "in the body and increased", "the body and increased urinary", "body and increased urinary excretion", "and increased urinary excretion of", "increased urinary excretion of these", "urinary excretion of these gags.", "excretion of these gags. symptoms", "of these gags. symptoms and", "these gags. symptoms and signs", "gags. symptoms and signs include", "symptoms and signs include hepatosplenomegaly", "signs include hepatosplenomegaly dwarfism", "hepatosplenomegaly dwarfism unique", "dwarfism unique facial features", "unique facial features corneal", "facial features corneal clouding", "clouding retinopathy progressive", "retinopathy progressive mental retardation", "progressive mental retardation appears during", "mental retardation appears during childhood", "retardation appears during childhood and", "appears during childhood and early", "during childhood and early death", "childhood and early death can", "and early death can occur", "early death can occur due", "death can occur due to", "can occur due to organ", "occur due to organ damage", "to organ damage campos", "organ damage campos &", "damage campos & monaga", "campos & monaga 2012 .", "& monaga 2012 . mps", "monaga 2012 . mps i", "2012 . mps i is", ". mps i is divided", "mps i is divided into", "i is divided into three", "is divided into three subtypes", "into three subtypes ranging", "three subtypes ranging from", "subtypes ranging from severe", "ranging from severe to mild", "from severe to mild phenotypes", "to mild phenotypes mucopolysaccharidosis", "mild phenotypes mucopolysaccharidosis type", "phenotypes mucopolysaccharidosis type ih", "mucopolysaccharidosis type ih mpsih", "ih mpsih hurler", "mim:607014 mucopolysaccharidosis type", "607014 mucopolysaccharidosis type", "mucopolysaccharidosis type ih/s mpsih/s", "ih/s mpsih/s hurlerscheie", "hurlerscheie syndrome mim: 607015", "mim: 607015 and mucopolysaccharidosis", " 607015 and mucopolysaccharidosis", "607015 and mucopolysaccharidosis type", "mucopolysaccharidosis type is mpsis", "is mpsis scheie", "scheie syndrome mim: 607016", "607016 respectively mckusick", "respectively mckusick 1972 ." ] }, { "record_id": "GLY_000594_1_1617", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "2206307", "r hsa", "hsa 2206307", "r hsa 2206307" ] }, { "record_id": "GLY_000594_1_1617", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mps iiia", "sanfilippo syndrome", "syndrome a", "sanfilippo syndrome a", "iiia sanfilippo", "mps iiia sanfilippo", "iiia sanfilippo syndrome", "mucopolysaccharidosis iii", "mps iii", "was described", "described in", "in 1963", "1963 by", "by a", "a pediatrician", "pediatrician named", "named sylvester", "sylvester sanfilippo", "j. pediat.", "pediat. 63:", "63: 837", "837 838", "no reference", "reference .", ". mucopolysaccharidosis", "mucopolysaccharidosis iiia", "is a", "a rare", "autosomal recessive", "recessive lysosomal", "lysosomal storage", "storage disease", "disease characterised", "characterised by", "by severe", "severe cns", "cns degeneration", "degeneration in", "in early", "early childhood", "childhood leading", "leading to", "to death", "death between", "between 10", "10 and", "and 20", "20 years", "years of", "of age.", "age. a", "a deficiency", "deficiency of", "of the", "the enzyme", "enzyme n", "n sulphoglucosamine", "sulphoglucosamine sulphohydrolase", "which normally", "normally hydrolyses", "hydrolyses the", "the sulfate", "sulfate group", "group from", "from the", "the terminal", "terminal n", "sulphoglucosamine residue", "residue of", "of heparan", "heparan sulfate", "leads to", "to the", "the build", "build up", "up of", "of hs", "hs in", "in cells", "cells and", "and tissues", "tissues and", "and its", "its presence", "presence in", "in urine", "van de", "de kamp", "kamp et", "et al.", "al. 1981", "yogalingam &", "& hopwood", "hopwood 2001", "de ruijter", "ruijter et", "al. 2011", "2011 .", ". the", "the gene", "gene encoding", "encoding n", "n sulfoglucosamine", "sulfoglucosamine sulfohydrolase", "was cloned", "cloned in", "in 1995", "scott et", "et al.1995", "shown to", "to contain", "contain 8", "8 exons", "exons spanning", "spanning approximately", "approximately 11", "11 kb", "karageorgos et", "al. 1996", "1996 .", "iii mps", "iii sanfilippo", "syndrome was", "was described in", "described in 1963", "in 1963 by", "1963 by a", "by a pediatrician", "a pediatrician named", "pediatrician named sylvester", "named sylvester sanfilippo", "sanfilippo j.", "j. pediat. 63:", "pediat. 63: 837", "63: 837 838", "838 1963", "1963 no", "no reference .", "reference . mucopolysaccharidosis", ". mucopolysaccharidosis iiia", "iiia mps", "a mim:252900", "mim:252900 is", "252900 is", "is a rare", "rare autosomal", "autosomal recessive lysosomal", "recessive lysosomal storage", "lysosomal storage disease", "storage disease characterised", "disease characterised by", "characterised by severe", "by severe cns", "severe cns degeneration", "cns degeneration in", "degeneration in early", "in early childhood", "early childhood leading", "childhood leading to", "leading to 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              a", "and retinal macular degeneration.

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et al. 2005 .", "et al. 2005 . senp2", "al. 2005 . senp2 also", "2005 . senp2 also shuttles", "senp2 also shuttles itahana", "also shuttles itahana et", "shuttles itahana et al.", "et al. 2006 and", "al. 2006 and is", "2006 and is mainly", "and is mainly located on", "is mainly located on nucleoplasmic", "mainly located on nucleoplasmic filaments", "located on nucleoplasmic filaments of", "on nucleoplasmic filaments of the", "nucleoplasmic filaments of the nuclear", "filaments of the nuclear pore", "of the nuclear pore complex", "nuclear pore complex hang", "pore complex hang and", "complex hang and dasso", "and dasso 2002 zhang", "dasso 2002 zhang et", "2002 zhang et al.", "zhang et al. 2002 .", "et al. 2002 . senp5", "al. 2002 . senp5 is", "2002 . senp5 is located", ". senp5 is located mostly", "senp5 is located mostly in", "is located mostly in the", "located mostly in the nucleolus", "in the nucleolus di", "the nucleolus di bacco", "nucleolus di bacco et", "di bacco et al. 2006", 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"phraselist": [ "gly_000594", "hsa", "3247509", "r hsa", "hsa 3247509", "r hsa 3247509" ] }, { "record_id": "GLY_000594_1_1626", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "chromatin modifying", "modifying enzymes", "chromatin modifying enzymes", "eukaryotic dna", "dna is", "is associated", "associated with", "with histone", "histone proteins", "proteins and", "and organized", "organized into", "into a", "a complex", "complex nucleoprotein", "nucleoprotein structure", "structure called", "called chromatin.", "chromatin. this", "this structure", "structure decreases", "decreases the", "the accessibility", "accessibility of", "of dna", "dna but", "but also", "also helps", "helps to", "to protect", "protect it", "it from", "from damage.", "damage. access", "access to", "to dna", "is achieved", "achieved by", "by highly", "highly regulated", "regulated local", "local chromatin", "chromatin decondensation.", "decondensation.

              the", "

              the 'building", "'building block'", "block' of", "of chromatin", "chromatin is", "is the", "the nucleosome.", "nucleosome. this", "this contains", "contains ~150", "~150 bp", "bp of", "dna wrapped", "wrapped around", "around a", "a histone", "histone octamer", "octamer which", "which consists", "consists of", "of two", "two each", "each of", "of the", "the core", "core histones", "histones h2a", "h3 and", "and h4", "h4 in", "in a", "a 1.65", "1.65 left", "left handed", "handed superhelical", "superhelical turn", "luger et", "et al.", "al. 1997", "andrews &", "& luger", "luger 2011", "2011 .

              most", ".

              most organisms", "organisms have", "have multiple", "multiple genes", "genes encoding", "encoding the", "the major", "major histone", "histone proteins.", "proteins. the", "the replication", "replication dependent", "dependent genes", "genes for", "for the", "the five", "five histone", "proteins are", "are clustered", "clustered together", "together in", "in the", "the genome", "genome in", "in all", "all metazoans.", "metazoans. human", "human replication", "dependent histones", "histones occur", "occur in", "a large", "large cluster", "cluster on", "on chromosome", "chromosome 6", "6 termed", "termed hist1", "a smaller", "smaller cluster", "cluster hist2", "hist2 on", "chromosome 1q21", "and a", "a third", "third small", "small cluster", "cluster hist3", "hist3 on", "chromosome 1q42", "marzluff et", "al. 2002", "2002 .", ". histone", "histone genes", "genes are", "are named", "named systematically", "systematically according", "according to", "to their", "their cluster", "cluster and", "and location", "location within", "within the", "the cluster.

              the", "cluster.

              the 'major'", "'major' histone", "are expressed", "expressed primarily", "primarily during", "during the", "the s", "s phase", "phase of", "the cell", "cell cycle", "cycle and", "and code", "code for", "the bulk", "bulk of", "of cellular", "cellular histones.", "histones. histone", "histone variants", "variants are", "are usually", "usually present", "present as", "as single", "single copy", "copy genes", "genes that", "that are", "are not", "not restricted", "restricted in", "in their", "their expression", "expression to", "to s", "contain introns", "introns and", "and are", "are often", "often polyadenylated", "old &", "& woodland", "woodland 1984", "1984 .", ". some", "some variants", "variants have", "have significant", "significant differences", "differences in", "in primary", "primary sequence", "sequence and", "and distinct", "distinct biophysical", "biophysical characteristics", "characteristics that", "are thought", "thought to", "to alter", "alter the", "the properties", "properties of", "of nucleosomes.", "nucleosomes. others", "others localize", "localize to", "to specific", "specific regions", "regions of", "the genome.", "genome. some", "variants can", "can exchange", "exchange with", "with pre", "pre existing", "existing major", "major histones", "histones during", "during development", "development and", "and differentiation", "referred to", "to as", "as replacement", "replacement histones", "kamakaka &", "& biggins", "biggins 2005", "2005 .", ". these", "these variants", "can become", "become the", "the predominant", "predominant species", "species in", "in differentiated", "differentiated cells", "pina &", "& suau", "suau 1987", "wunsch et", "al. 1991", "1991 .", "variants may", "may have", "have specialized", "specialized functions", "functions in", "in regulating", "regulating chromatin", "chromatin dynamics.", "dynamics.

              the", "

              the h2a", "h2a histone", "histone family", "family has", "has the", "the highest", "highest sequence", "sequence divergence", "divergence and", "and largest", "largest number", "number of", "of variants.", "variants. h2a.z", "h2a.z and", "and h2a.xh2a", "h2a.xh2a are", "are considered", "considered 'universal", "'universal variants'", "found in", "in almost", "almost all", "all organisms", "talbert &", "& henikoff", "henikoff 2010", "2010 .", ". variants", "variants differ", "differ mostly", "mostly in", "the c", "c terminus", "including the", "the docking", "docking domain", "implicated in", "in interactions", "interactions with", "with the", "h3 h4", "h4 x2", "x2 tetramer", "tetramer within", "the nucleosome", "and in", "the l1", "l1 loop", "which is", "the interaction", "interaction interface", "interface of", "of h2a", "h2a h2b", "h2b dimers", "bonisch &", "& hake", "hake 2012", "2012 .", ". canonical", "canonical h2a", "h2a proteins", "expressed almost", "almost exclusively", "exclusively during", "during s", "s phase.", "phase. there", "there are", "are several", "several nearly", "nearly identical", "identical variants", ". no", "no functional", "functional specialization", "specialization of", "of these", "these canonical", "h2a isoforms", "isoforms has", "has been", "been demonstrated", "reversible histone", "histone modifications", "modifications such", "such as", "as acetylation", "acetylation and", "and methylation", "methylation regulate", "regulate transcription", "transcription from", "from genomic", "genomic dna", "defining the", "the 'readability'", "'readability' of", "of genes", "genes in", "in specific", "specific tissues", "kouzarides 2007", "marmorstein &", "& trievel", "trievel 2009", "butler et", "al. 2012", "2012 .

              n.b.", ".

              n.b. the", "the coordinates", "coordinates of", "of post", "post translational", "translational modifications", "modifications represented", "represented here", "here follow", "follow reactome", "reactome standardized", "standardized naming", "which includes", "includes the", "the uniprot", "uniprot standard", "standard practice", "practice whereby", "whereby coordinates", "coordinates refer", "refer to", "to the", "the translated", "translated protein", "protein before", "before any", "any further", "further processing.", "processing. histone", "histone literature", "literature typically", "typically refers", "refers to", "to coordinates", "the protein", "protein after", "after the", "the initiating", "initiating methionine", "methionine has", "been removed", "therefore the", "post translated", "translated histone", "histone residues", "residues described", "described here", "here are", "are frequently", "frequently +1", "+1 when", "when compared", "compared with", "the literature.", "literature. for", "for more", "more information", "information on", "on reactome's", "reactome's standards", "standards for", "for naming", "naming pathway", "pathway events", "the molecules", "molecules that", "that participate", "participate in", "in them", "them and", "and representation", "representation of", "please refer", "to naming", "naming conventions", "conventions on", "on the", "the reactome", "reactome wiki", "wiki or", "or jupe", "jupe et", "al. 2014.", "eukaryotic dna is", "dna is associated", "is associated with", "associated with histone", "with histone proteins", "histone proteins and", "proteins and organized", "and organized into", "organized into a", "into a complex", "a complex nucleoprotein", "complex nucleoprotein structure", "nucleoprotein structure called", "structure called chromatin.", "called chromatin. this", "chromatin. this structure", "this structure decreases", "structure decreases the", "decreases the accessibility", "the accessibility of", "accessibility of dna", "of dna but", "dna but also", "but also helps", "also helps to", "helps to protect", "to protect it", "protect it from", "it from damage.", "from damage. access", "damage. access to", "access to dna", "to dna is", "dna is achieved", "is achieved by", "achieved by highly", "by highly regulated", "highly regulated local", "regulated local chromatin", "local chromatin decondensation.", "chromatin decondensation.

              the", "decondensation.

              the 'building", "

              the 'building block'", "'building block' of", "block' of chromatin", "of chromatin is", "chromatin is the", "is the nucleosome.", "the nucleosome. this", "nucleosome. this contains", "this contains ~150", "contains ~150 bp", "~150 bp of", "bp of dna", "of dna wrapped", "dna wrapped around", "wrapped around a", "around a histone", "a histone octamer", "histone octamer which", "octamer which consists", "which consists of", "consists of two", "of two each", "two each of", "each of the", "of the core", "the core histones", "core histones h2a", "h2b h3", "h3 and h4", "and h4 in", "h4 in a", "in a 1.65", "a 1.65 left", "1.65 left handed", "left handed superhelical", "handed superhelical turn", "turn luger", "luger et al.", "et al. 1997", "1997 andrews", "andrews & luger", "& luger 2011", "luger 2011 .

              most", "2011 .

              most organisms", ".

              most organisms have", "organisms have multiple", "have multiple genes", "multiple genes encoding", "genes encoding the", "encoding the major", "the major histone", "major histone proteins.", "histone proteins. the", "proteins. the replication", "the replication dependent", "replication dependent genes", "dependent genes for", "genes for the", "for the five", "the five histone", "five histone proteins", "histone proteins are", "proteins are clustered", "are clustered together", "clustered together in", "together in the", "in the genome", "the genome in", "genome in all", "in all metazoans.", "all metazoans. human", "metazoans. human replication", "human replication dependent", "replication dependent histones", "dependent histones occur", "histones occur in", "occur in a", "in a large", "a large cluster", "large cluster on", "cluster on chromosome", "on chromosome 6", "chromosome 6 termed", "6 termed hist1", "hist1 a", "a smaller cluster", "smaller cluster hist2", "cluster hist2 on", "hist2 on chromosome", "on chromosome 1q21", "1q21 and", "and a third", "a third small", "third small cluster", "small cluster hist3", "cluster hist3 on", "hist3 on chromosome", "on chromosome 1q42", "1q42 marzluff", "marzluff et al.", "et al. 2002", "al. 2002 .", "2002 . histone", ". histone genes", "histone genes are", "genes are named", "are named systematically", "named systematically according", "systematically according to", "according to their", "to their cluster", "their cluster and", "cluster and location", "and location within", "location within the", "within the cluster.

              the", "the cluster.

              the 'major'", "cluster.

              the 'major' histone", "'major' histone genes", "genes are expressed", "are expressed primarily", "expressed primarily during", "primarily during the", "during the s", "the s phase", "s phase of", "phase of the", "of the cell", "the cell cycle", "cell cycle and", "cycle and code", "and code for", "code for the", "for the bulk", "the bulk of", "bulk of cellular", "of cellular histones.", "cellular histones. histone", "histones. histone variants", "histone variants are", "variants are usually", "are usually present", "usually present as", "present as single", "as single copy", "single copy genes", "copy genes that", "genes that are", "that are not", "are not restricted", "not restricted in", "restricted in their", "in their expression", "their expression to", "expression to s", "to s phase", "phase contain", "contain introns and", "introns and are", "and are often", "are often polyadenylated", "polyadenylated old", "old & woodland", "& woodland 1984", "woodland 1984 .", "1984 . some", ". some variants", "some variants have", "variants have significant", "have significant differences", "significant differences in", "differences in primary", "in primary sequence", "primary sequence and", "sequence and distinct", "and distinct biophysical", "distinct biophysical characteristics", "biophysical characteristics that", "characteristics that are", "that are thought", "are thought to", "thought to alter", "to alter the", "alter the properties", "the properties of", "properties of nucleosomes.", "of nucleosomes. others", "nucleosomes. others localize", "others localize to", "localize to specific", "to specific regions", "specific regions of", "regions of the", "of the genome.", "the genome. some", "genome. some variants", "some variants can", "variants can exchange", "can exchange with", "exchange with pre", "with pre existing", "pre existing major", "existing major histones", "major histones during", "histones during development", "during development and", "development and differentiation", "differentiation referred", "referred to as", "to as replacement", "as replacement histones", "histones kamakaka", "kamakaka & biggins", "& biggins 2005", "biggins 2005 .", "2005 . these", ". these variants", "these variants can", "variants can become", "can become the", "become the predominant", "the predominant species", "predominant species in", "species in differentiated", "in differentiated cells", "cells pina", "pina & suau", "& suau 1987", "1987 wunsch", "wunsch et al.", "et al. 1991", "al. 1991 .", "1991 . histone", ". histone variants", "histone variants may", "variants may have", "may have specialized", "have specialized functions", "specialized functions in", "functions in regulating", "in regulating chromatin", "regulating chromatin dynamics.", "chromatin dynamics.

              the", "dynamics.

              the h2a", "

              the h2a histone", "h2a histone family", "histone family has", "family has the", "has the highest", "the highest sequence", "highest sequence divergence", "sequence divergence and", "divergence and largest", "and largest number", "largest number of", "number of variants.", "of variants. h2a.z", "variants. h2a.z and", "h2a.z and h2a.xh2a", "and h2a.xh2a are", "h2a.xh2a are considered", "are considered 'universal", "considered 'universal variants'", "variants' found", "found in almost", "in almost all", "almost all organisms", "organisms talbert", "talbert & henikoff", "& henikoff 2010", "henikoff 2010 .", "2010 . variants", ". variants differ", "variants differ mostly", "differ mostly in", "mostly in the", "in the c", "the c terminus", "terminus including", "including the docking", "the docking domain", "domain implicated", "implicated in interactions", "in interactions with", "interactions with the", "the h3", "h3 h4 x2", "h4 x2 tetramer", "x2 tetramer within", "tetramer within the", "within the nucleosome", "nucleosome and", "and in the", "in the l1", "the l1 loop", "loop which", "which is the", "is the interaction", "the interaction interface", "interaction interface of", "interface of h2a", "of h2a h2b", "h2a h2b dimers", "dimers bonisch", "bonisch & hake", "& hake 2012", "hake 2012 .", "2012 . canonical", ". canonical h2a", "canonical h2a proteins", "h2a proteins are", "proteins are expressed", "are expressed almost", "expressed almost exclusively", "almost exclusively during", "exclusively during s", "during s phase.", "s phase. there", "phase. there are", "there are several", "are several nearly", "several nearly identical", "nearly identical variants", "variants marzluff", "2002 . no", ". no functional", "no functional specialization", "functional specialization of", "specialization of these", "of these canonical", "these canonical h2a", "canonical h2a isoforms", "h2a isoforms has", "isoforms has been", "has been demonstrated", "demonstrated bonisch", ". reversible", "reversible histone modifications", "histone modifications such", "modifications such as", "such as acetylation", "as acetylation and", "acetylation and methylation", "and methylation regulate", "methylation regulate transcription", "regulate transcription from", "transcription from genomic", "from genomic dna", "dna defining", "defining the 'readability'", "the 'readability' of", "'readability' of genes", "of genes in", "genes in specific", "in specific tissues", "tissues kouzarides", "2007 marmorstein", "marmorstein & trievel", "& trievel 2009", "2009 butler", "butler et al.", "et al. 2012", "al. 2012 .

              n.b.", "2012 .

              n.b. the", ".

              n.b. the coordinates", "the coordinates of", "coordinates of post", "of post translational", "post translational modifications", "translational modifications represented", "modifications represented here", "represented here follow", "here follow reactome", "follow reactome standardized", "reactome standardized naming", "naming which", "which includes the", "includes the uniprot", "the uniprot standard", "uniprot standard practice", "standard practice whereby", "practice whereby coordinates", "whereby coordinates refer", "coordinates refer to", "refer to the", "to the translated", "the translated protein", "translated protein before", "protein before any", "before any further", "any further processing.", "further processing. histone", "processing. histone literature", "histone literature typically", "literature typically refers", "typically refers to", "refers to coordinates", "to coordinates of", "coordinates of the", "of the protein", "the protein after", "protein after the", "after the initiating", "the initiating methionine", "initiating methionine has", "methionine has been", "has been removed", "removed therefore", "therefore the coordinates", "of post translated", "post translated histone", "translated histone residues", "histone residues described", "residues described here", "described here are", "here are frequently", "are frequently +1", "frequently +1 when", "+1 when compared", "when compared with", "compared with the", "with the literature.", "the literature. for", "literature. for more", "for more information", "more information on", "information on reactome's", "on reactome's standards", "reactome's standards for", "standards for naming", "for naming pathway", "naming pathway events", "events the", "the molecules that", "molecules that participate", "that participate in", "participate in them", "in them and", "them and representation", "and representation of", "representation of post", "modifications please", "please refer to", "refer to naming", "to naming conventions", "naming conventions on", "conventions on the", "on the reactome", "the reactome wiki", "reactome wiki or", "wiki or jupe", "or jupe et", "jupe et al.", "et al. 2014.", "eukaryotic dna is associated", "dna is associated with", "is associated with histone", "associated with histone proteins", "with histone proteins and", "histone proteins and organized", "proteins and organized into", "and organized into a", "organized into a complex", "into a complex nucleoprotein", "a complex nucleoprotein structure", "complex nucleoprotein structure called", "nucleoprotein structure called chromatin.", "structure called chromatin. this", "called chromatin. this structure", "chromatin. this structure decreases", "this structure decreases the", "structure decreases the accessibility", "decreases the accessibility of", "the accessibility of dna", "accessibility of dna but", "of dna but also", "dna but also helps", "but also helps to", "also helps to protect", "helps to protect it", "to protect it from", "protect it from damage.", "it from damage. access", "from damage. access to", "damage. access to dna", "access to dna is", "to dna is achieved", "dna is achieved by", "is achieved by highly", "achieved by highly regulated", "by highly regulated local", "highly regulated local chromatin", "regulated local chromatin decondensation.", "local chromatin decondensation.

              the", "chromatin decondensation.

              the 'building", "decondensation.

              the 'building block'", "

              the 'building block' of", "'building block' of chromatin", "block' of chromatin is", "of chromatin is the", "chromatin is the nucleosome.", "is the nucleosome. this", "the nucleosome. this contains", "nucleosome. this contains ~150", "this contains ~150 bp", "contains ~150 bp of", "~150 bp of dna", "bp of dna wrapped", "of dna wrapped around", "dna wrapped around a", "wrapped around a histone", "around a histone octamer", "a histone octamer which", "histone octamer which consists", "octamer which consists of", "which consists of two", "consists of two each", "of two each of", "two each of the", "each of the core", "of the core histones", "the core histones h2a", "histones h2a h2b", "h2b h3 and", "h3 and h4 in", "and h4 in a", "h4 in a 1.65", "in a 1.65 left", "a 1.65 left handed", "1.65 left handed superhelical", "left handed superhelical turn", "superhelical turn luger", "turn luger et", "luger et al. 1997", "al. 1997 andrews", "1997 andrews &", "andrews & luger 2011", "& luger 2011 .

              most", "luger 2011 .

              most organisms", "2011 .

              most organisms have", ".

              most organisms have multiple", "organisms have multiple genes", "have multiple genes encoding", "multiple genes encoding the", "genes encoding the major", "encoding the major histone", "the major histone proteins.", "major histone proteins. the", "histone proteins. the replication", "proteins. the replication dependent", "the replication dependent genes", "replication dependent genes for", "dependent genes for the", "genes for the five", "for the five histone", "the five histone proteins", "five histone proteins are", "histone proteins are clustered", "proteins are clustered together", "are clustered together in", "clustered together in the", "together in the genome", "in the genome in", "the genome in all", "genome in all metazoans.", "in all metazoans. human", "all metazoans. human replication", "metazoans. human replication dependent", "human replication dependent histones", "replication dependent histones occur", "dependent histones occur in", "histones occur in a", "occur in a large", "in a large cluster", "a large cluster on", "large cluster on chromosome", "cluster on chromosome 6", "on chromosome 6 termed", "chromosome 6 termed hist1", "termed hist1 a", "hist1 a smaller", "a smaller cluster hist2", "smaller cluster hist2 on", "cluster hist2 on chromosome", "hist2 on chromosome 1q21", "chromosome 1q21 and", "1q21 and a", "and a third small", "a third small cluster", "third small cluster hist3", "small cluster hist3 on", "cluster hist3 on chromosome", "hist3 on chromosome 1q42", "chromosome 1q42 marzluff", "1q42 marzluff et", "marzluff et al. 2002", "et al. 2002 .", "al. 2002 . histone", "2002 . histone genes", ". histone genes are", "histone genes are named", "genes are named systematically", "are named systematically according", "named systematically according to", "systematically according to their", "according to their cluster", "to their cluster and", "their cluster and location", "cluster and location within", "and location within the", "location within the cluster.

              the", "within the cluster.

              the 'major'", "the cluster.

              the 'major' histone", "cluster.

              the 'major' histone genes", "'major' histone genes are", "histone genes are expressed", "genes are expressed primarily", "are expressed primarily during", "expressed primarily during the", "primarily during the s", "during the s phase", "the s phase of", "s phase of the", "phase of the cell", "of the cell cycle", "the cell cycle and", "cell cycle and code", "cycle and code for", "and code for the", "code for the bulk", "for the bulk of", "the bulk of cellular", "bulk of cellular histones.", "of cellular histones. histone", "cellular histones. histone variants", "histones. histone variants are", "histone variants are usually", "variants are usually present", "are usually present as", "usually present as single", "present as single copy", "as single copy genes", "single copy genes that", "copy genes that are", "genes that are not", "that are not restricted", "are not restricted in", "not restricted in their", "restricted in their expression", "in their expression to", "their expression to s", "expression to s phase", "s phase contain", "phase contain introns", "contain introns and are", "introns and are often", "and are often polyadenylated", "often polyadenylated old", "polyadenylated old &", "old & woodland 1984", "& woodland 1984 .", "woodland 1984 . some", "1984 . some variants", ". some variants have", "some variants have significant", "variants have significant differences", "have significant differences in", "significant differences in primary", "differences in primary sequence", "in primary sequence and", "primary sequence and distinct", "sequence and distinct biophysical", "and distinct biophysical characteristics", "distinct biophysical characteristics that", "biophysical characteristics that are", "characteristics that are thought", "that are thought to", "are thought to alter", "thought to alter the", "to alter the properties", "alter the properties of", "the properties of nucleosomes.", "properties of nucleosomes. others", "of nucleosomes. others localize", "nucleosomes. others localize to", "others localize to specific", "localize to specific regions", "to specific regions of", "specific regions of the", "regions of the genome.", "of the genome. some", "the genome. some variants", "genome. some variants can", "some variants can exchange", "variants can exchange with", "can exchange with pre", "exchange with pre existing", "with pre existing major", "pre existing major histones", "existing major histones during", "major histones during development", "histones during development and", "during development and differentiation", "and differentiation referred", "differentiation referred to", "referred to as replacement", "to as replacement histones", "replacement histones kamakaka", "histones kamakaka &", "kamakaka & biggins 2005", "& biggins 2005 .", "biggins 2005 . these", "2005 . these variants", ". these variants can", "these variants can become", "variants can become the", "can become the predominant", "become the predominant species", "the predominant species in", "predominant species in differentiated", "species in differentiated cells", "differentiated cells pina", "cells pina &", "pina & suau 1987", "suau 1987 wunsch", "1987 wunsch et", "wunsch et al. 1991", "et al. 1991 .", "al. 1991 . histone", "1991 . histone variants", ". histone variants may", "histone variants may have", "variants may have specialized", "may have specialized functions", "have specialized functions in", "specialized functions in regulating", "functions in regulating chromatin", "in regulating chromatin dynamics.", "regulating chromatin dynamics.

              the", "chromatin dynamics.

              the h2a", "dynamics.

              the h2a histone", "

              the h2a histone family", "h2a histone family has", "histone family has the", "family has the highest", "has the highest sequence", "the highest sequence divergence", "highest sequence divergence and", "sequence divergence and largest", "divergence and largest number", "and largest number of", "largest number of variants.", "number of variants. h2a.z", "of variants. h2a.z and", "variants. h2a.z and h2a.xh2a", "h2a.z and h2a.xh2a are", "and h2a.xh2a are considered", "h2a.xh2a are considered 'universal", "are considered 'universal variants'", "'universal variants' found", "variants' found in", "found in almost all", "in almost all organisms", "all organisms talbert", "organisms talbert &", "talbert & henikoff 2010", "& henikoff 2010 .", "henikoff 2010 . variants", "2010 . variants differ", ". variants differ mostly", "variants differ mostly in", "differ mostly in the", "mostly in the c", "in the c terminus", "c terminus including", "terminus including the", "including the docking domain", "docking domain implicated", "domain implicated in", "implicated in interactions with", "in interactions with the", "with the h3", "the h3 h4", "h3 h4 x2 tetramer", "h4 x2 tetramer within", "x2 tetramer within the", "tetramer within the nucleosome", "the nucleosome and", "nucleosome and in", "and in the l1", "in the l1 loop", "l1 loop which", "loop which is", "which is the interaction", "is the interaction interface", "the interaction interface of", "interaction interface of h2a", "interface of h2a h2b", "of h2a h2b dimers", "h2b dimers bonisch", "dimers bonisch &", "bonisch & hake 2012", "& hake 2012 .", "hake 2012 . canonical", "2012 . canonical h2a", ". canonical h2a proteins", "canonical h2a proteins are", "h2a proteins are expressed", "proteins are expressed almost", "are expressed almost exclusively", "expressed almost exclusively during", "almost exclusively during s", "exclusively during s phase.", "during s phase. there", "s phase. there are", "phase. there are several", "there are several nearly", "are several nearly identical", "several nearly identical variants", "identical variants marzluff", "variants marzluff et", "al. 2002 . no", "2002 . no functional", ". no functional specialization", "no functional specialization of", "functional specialization of these", "specialization of these canonical", "of these canonical h2a", "these canonical h2a isoforms", "canonical h2a isoforms has", "h2a isoforms has been", "isoforms has been demonstrated", "been demonstrated bonisch", "demonstrated bonisch &", "2012 . reversible", ". reversible histone", "reversible histone modifications such", "histone modifications such as", "modifications such as acetylation", "such as acetylation and", "as acetylation and methylation", "acetylation and methylation regulate", "and methylation regulate transcription", "methylation regulate transcription from", "regulate transcription from genomic", "transcription from genomic dna", "genomic dna defining", "dna defining the", "defining the 'readability' of", "the 'readability' of genes", "'readability' of genes in", "of genes in specific", "genes in specific tissues", "specific tissues kouzarides", "tissues kouzarides 2007", "kouzarides 2007 marmorstein", "2007 marmorstein &", "marmorstein & trievel 2009", "trievel 2009 butler", "2009 butler et", "butler et al. 2012", "et al. 2012 .

              n.b.", "al. 2012 .

              n.b. the", "2012 .

              n.b. the coordinates", ".

              n.b. the coordinates of", "the coordinates of post", "coordinates of post translational", "of post translational modifications", "post translational modifications represented", "translational modifications represented here", "modifications represented here follow", "represented here follow reactome", "here follow reactome standardized", "follow reactome standardized naming", "standardized naming which", "naming which includes", "which includes the uniprot", "includes the uniprot standard", "the uniprot standard practice", "uniprot standard practice whereby", "standard practice whereby coordinates", "practice whereby coordinates refer", "whereby coordinates refer to", "coordinates refer to the", "refer to the translated", "to the translated protein", "the translated protein before", "translated protein before any", "protein before any further", "before any further processing.", "any further processing. histone", "further processing. histone literature", "processing. histone literature typically", "histone literature typically refers", "literature typically refers to", "typically refers to coordinates", "refers to coordinates of", "to coordinates of the", "coordinates of the protein", "of the protein after", "the protein after the", "protein after the initiating", "after the initiating methionine", "the initiating methionine has", "initiating methionine has been", "methionine has been removed", "been removed therefore", "removed therefore the", "therefore the coordinates of", "coordinates of post translated", "of post translated histone", "post translated histone residues", "translated histone residues described", "histone residues described here", "residues described here are", "described here are frequently", "here are frequently +1", "are frequently +1 when", "frequently +1 when compared", "+1 when compared with", "when compared with the", "compared with the literature.", "with the literature. for", "the literature. for more", "literature. for more information", "for more information on", "more information on reactome's", "information on reactome's standards", "on reactome's standards for", "reactome's standards for naming", "standards for naming pathway", "for naming pathway events", "pathway events the", "events the molecules", "the molecules that participate", "molecules that participate in", "that participate in them", "participate in them and", "in them and representation", "them and representation of", "and representation of post", "representation of post translational", "translational modifications please", "modifications please refer", "please refer to naming", "refer to naming conventions", "to naming conventions on", "naming conventions on the", "conventions on the reactome", "on the reactome wiki", "the reactome wiki or", "reactome wiki or jupe", "wiki or jupe et", "or jupe et al.", "jupe et al. 2014.", "eukaryotic dna is associated with", "dna is associated with histone", "is associated with histone proteins", "associated with histone proteins and", "with histone proteins and organized", "histone proteins and organized into", "proteins and organized into a", "and organized into a complex", "organized into a complex nucleoprotein", "into a complex nucleoprotein structure", "a complex nucleoprotein structure called", "complex nucleoprotein structure called chromatin.", "nucleoprotein structure called chromatin. this", "structure called chromatin. this structure", "called chromatin. this structure decreases", "chromatin. this structure decreases the", "this structure decreases the accessibility", "structure decreases the accessibility of", "decreases the accessibility of dna", "the accessibility of dna but", "accessibility of dna but also", "of dna but also helps", "dna but also helps to", "but also helps to protect", "also helps to protect it", "helps to protect it from", "to protect it from damage.", "protect it from damage. access", "it from damage. access to", "from damage. access to dna", "damage. access to dna is", "access to dna is achieved", "to dna is achieved by", "dna is achieved by highly", "is achieved by highly regulated", "achieved by highly regulated local", "by highly regulated local chromatin", "highly regulated local chromatin decondensation.", "regulated local chromatin decondensation.

              the", "local chromatin decondensation.

              the 'building", "chromatin decondensation.

              the 'building block'", "decondensation.

              the 'building block' of", "

              the 'building block' of chromatin", "'building block' of chromatin is", "block' of chromatin is the", "of chromatin is the nucleosome.", "chromatin is the nucleosome. this", "is the nucleosome. this contains", "the nucleosome. this contains ~150", "nucleosome. this contains ~150 bp", "this contains ~150 bp of", "contains ~150 bp of dna", "~150 bp of dna wrapped", "bp of dna wrapped around", "of dna wrapped around a", "dna wrapped around a histone", "wrapped around a histone octamer", "around a histone octamer which", "a histone octamer which consists", "histone octamer which consists of", "octamer which consists of two", "which consists of two each", "consists of two each of", "of two each of the", "two each of the core", "each of the core histones", "of the core histones h2a", "core histones h2a h2b", "h2a h2b h3", "h2b h3 and h4", "h3 and h4 in a", "and h4 in a 1.65", "h4 in a 1.65 left", "in a 1.65 left handed", "a 1.65 left handed superhelical", "1.65 left handed superhelical turn", "handed superhelical turn luger", "superhelical turn luger et", "turn luger et al.", "et al. 1997 andrews", "al. 1997 andrews &", "1997 andrews & luger", "andrews & luger 2011 .

              most", "& luger 2011 .

              most organisms", "luger 2011 .

              most organisms have", "2011 .

              most organisms have multiple", ".

              most organisms have multiple genes", "organisms have multiple genes encoding", "have multiple genes encoding the", "multiple genes encoding the major", "genes encoding the major histone", "encoding the major histone proteins.", "the major histone proteins. the", "major histone proteins. the replication", "histone proteins. the replication dependent", "proteins. the replication dependent genes", "the replication dependent genes for", "replication dependent genes for the", "dependent genes for the five", "genes for the five histone", "for the five histone proteins", "the five histone proteins are", "five histone proteins are clustered", "histone proteins are clustered together", "proteins are clustered together in", "are clustered together in the", "clustered together in the genome", "together in the genome in", "in the genome in all", "the genome in all metazoans.", "genome in all metazoans. human", "in all metazoans. human replication", "all metazoans. human replication dependent", "metazoans. human replication dependent histones", "human replication dependent histones occur", "replication dependent histones occur in", "dependent histones occur in a", "histones occur in a large", "occur in a large cluster", "in a large cluster on", "a large cluster on chromosome", "large cluster on chromosome 6", "cluster on chromosome 6 termed", "on chromosome 6 termed hist1", "6 termed hist1 a", "termed hist1 a smaller", "hist1 a smaller cluster", "a smaller cluster hist2 on", "smaller cluster hist2 on chromosome", "cluster hist2 on chromosome 1q21", "on chromosome 1q21 and", "chromosome 1q21 and a", "1q21 and a third", "and a third small cluster", "a third small cluster hist3", "third small cluster hist3 on", "small cluster hist3 on chromosome", "cluster hist3 on chromosome 1q42", "on chromosome 1q42 marzluff", "chromosome 1q42 marzluff et", "1q42 marzluff et al.", "marzluff et al. 2002 .", "et al. 2002 . histone", "al. 2002 . histone genes", "2002 . histone genes are", ". histone genes are named", "histone genes are named systematically", "genes are named systematically according", "are named systematically according to", "named systematically according to their", "systematically according to their cluster", "according to their cluster and", "to their cluster and location", "their cluster and location within", "cluster and location within the", "and location within the cluster.

              the", "location within the cluster.

              the 'major'", "within the cluster.

              the 'major' histone", "the cluster.

              the 'major' histone genes", "cluster.

              the 'major' histone genes are", "'major' histone genes are expressed", "histone genes are expressed primarily", "genes are expressed primarily during", "are expressed primarily during the", "expressed primarily during the s", "primarily during the s phase", "during the s phase of", "the s phase of the", "s phase of the cell", "phase of the cell cycle", "of the cell cycle and", "the cell cycle and code", "cell cycle and code for", "cycle and code for the", "and code for the bulk", "code for the bulk of", "for the bulk of cellular", "the bulk of cellular histones.", "bulk of cellular histones. histone", "of cellular histones. histone variants", "cellular histones. histone variants are", "histones. histone variants are usually", "histone variants are usually present", "variants are usually present as", "are usually present as single", "usually present as single copy", "present as single copy genes", "as single copy genes that", "single copy genes that are", "copy genes that are not", "genes that are not restricted", "that are not restricted in", "are not restricted in their", "not restricted in their expression", "restricted in their expression to", "in their expression to s", "their expression to s phase", "to s phase contain", "s phase contain introns", "phase contain introns and", "contain introns and are often", "introns and are often polyadenylated", "are often polyadenylated old", "often polyadenylated old &", "polyadenylated old & woodland", "old & woodland 1984 .", "& woodland 1984 . some", "woodland 1984 . some variants", "1984 . some variants have", ". some variants have significant", "some variants have significant differences", "variants have significant differences in", "have significant differences in primary", "significant differences in primary sequence", "differences in primary sequence and", "in primary sequence and distinct", "primary sequence and distinct biophysical", "sequence and distinct biophysical characteristics", "and distinct biophysical characteristics that", "distinct biophysical characteristics that are", "biophysical characteristics that are thought", "characteristics that are thought to", "that are thought to alter", "are thought to alter the", "thought to alter the properties", "to alter the properties of", "alter the properties of nucleosomes.", "the properties of nucleosomes. others", "properties of nucleosomes. others localize", "of nucleosomes. others localize to", "nucleosomes. others localize to specific", "others localize to specific regions", "localize to specific regions of", "to specific regions of the", "specific regions of the genome.", "regions of the genome. some", "of the genome. some variants", "the genome. some variants can", "genome. some variants can exchange", "some variants can exchange with", "variants can exchange with pre", "can exchange with pre existing", "exchange with pre existing major", "with pre existing major histones", "pre existing major histones during", "existing major histones during development", "major histones during development and", "histones during development and differentiation", "development and differentiation referred", "and differentiation referred to", "differentiation referred to as", "referred to as replacement histones", "as replacement histones kamakaka", "replacement histones kamakaka &", "histones kamakaka & biggins", "kamakaka & biggins 2005 .", "& biggins 2005 . these", "biggins 2005 . these variants", "2005 . these variants can", ". these variants can become", "these variants can become the", "variants can become the predominant", "can become the predominant species", "become the predominant species in", "the predominant species in differentiated", "predominant species in differentiated cells", "in differentiated cells pina", "differentiated cells pina &", "cells pina & suau", "& suau 1987 wunsch", "suau 1987 wunsch et", "1987 wunsch et al.", "wunsch et al. 1991 .", "et al. 1991 . histone", "al. 1991 . histone variants", "1991 . histone variants may", ". histone variants may have", "histone variants may have specialized", "variants may have specialized functions", "may have specialized functions in", "have specialized functions in regulating", "specialized functions in regulating chromatin", "functions in regulating chromatin dynamics.", "in regulating chromatin dynamics.

              the", "regulating chromatin dynamics.

              the h2a", "chromatin dynamics.

              the h2a histone", "dynamics.

              the h2a histone family", "

              the h2a histone family has", "h2a histone family has the", "histone family has the highest", "family has the highest sequence", "has the highest sequence divergence", "the highest sequence divergence and", "highest sequence divergence and largest", "sequence divergence and largest number", "divergence and largest number of", "and largest number of variants.", "largest number of variants. h2a.z", "number of variants. h2a.z and", "of variants. h2a.z and h2a.xh2a", "variants. h2a.z and h2a.xh2a are", "h2a.z and h2a.xh2a are considered", "and h2a.xh2a are considered 'universal", "h2a.xh2a are considered 'universal variants'", "considered 'universal variants' found", "'universal variants' found in", "variants' found in almost", "found in almost all organisms", "almost all organisms talbert", "all organisms talbert &", "organisms talbert & henikoff", "talbert & henikoff 2010 .", "& henikoff 2010 . variants", "henikoff 2010 . variants differ", "2010 . variants differ mostly", ". variants differ mostly in", "variants differ mostly in the", "differ mostly in the c", "mostly in the c terminus", "the c terminus including", "c terminus including the", "terminus including the docking", "the docking domain implicated", "docking domain implicated in", "domain implicated in interactions", "implicated in interactions with the", "interactions with the h3", "with the h3 h4", "the h3 h4 x2", "h3 h4 x2 tetramer within", "h4 x2 tetramer within the", "x2 tetramer within the nucleosome", "within the nucleosome and", "the nucleosome and in", "nucleosome and in the", "and in the l1 loop", "the l1 loop which", "l1 loop which is", "loop which is the", "which is the interaction interface", "is the interaction interface of", "the interaction interface of h2a", "interaction interface of h2a h2b", "interface of h2a h2b dimers", "h2a h2b dimers bonisch", "h2b dimers bonisch &", "dimers bonisch & hake", "bonisch & hake 2012 .", "& hake 2012 . canonical", "hake 2012 . canonical h2a", "2012 . canonical h2a proteins", ". canonical h2a proteins are", "canonical h2a proteins are expressed", "h2a proteins are expressed almost", "proteins are expressed almost exclusively", "are expressed almost exclusively during", "expressed almost exclusively during s", "almost exclusively during s phase.", "exclusively during s phase. there", "during s phase. there are", "s phase. there are several", "phase. there are several nearly", "there are several nearly identical", "are several nearly identical variants", "nearly identical variants marzluff", "identical variants marzluff et", "variants marzluff et al.", "et al. 2002 . no", "al. 2002 . no functional", "2002 . no functional specialization", ". no functional specialization of", "no functional specialization of these", "functional specialization of these canonical", "specialization of these canonical h2a", "of these canonical h2a isoforms", "these canonical h2a isoforms has", "canonical h2a isoforms has been", "h2a isoforms has been demonstrated", "has been demonstrated bonisch", "been demonstrated bonisch &", "demonstrated bonisch & hake", "hake 2012 . reversible", "2012 . reversible histone", ". reversible histone modifications", "reversible histone modifications such as", "histone modifications such as acetylation", "modifications such as acetylation and", "such as acetylation and methylation", "as acetylation and methylation regulate", "acetylation and methylation regulate transcription", "and methylation regulate transcription from", "methylation regulate transcription from genomic", "regulate transcription from genomic dna", "from genomic dna defining", "genomic dna defining the", "dna defining the 'readability'", "defining the 'readability' of genes", "the 'readability' of genes in", "'readability' of genes in specific", "of genes in specific tissues", "in specific tissues kouzarides", "specific tissues kouzarides 2007", "kouzarides 2007 marmorstein &", "2007 marmorstein & trievel", "& trievel 2009 butler", "trievel 2009 butler et", "2009 butler et al.", "butler et al. 2012 .

              n.b.", "et al. 2012 .

              n.b. the", "al. 2012 .

              n.b. the coordinates", "2012 .

              n.b. the coordinates of", ".

              n.b. the coordinates of post", "the coordinates of post translational", "coordinates of post translational modifications", "of post translational modifications represented", "post translational modifications represented here", "translational modifications represented here follow", "modifications represented here follow reactome", "represented here follow reactome standardized", "here follow reactome standardized naming", "reactome standardized naming which", "standardized naming which includes", "naming which includes the", "which includes the uniprot standard", "includes the uniprot standard practice", "the uniprot standard practice whereby", "uniprot standard practice whereby coordinates", "standard practice whereby coordinates refer", "practice whereby coordinates refer to", "whereby coordinates refer to the", "coordinates refer to the translated", "refer to the translated protein", "to the translated protein before", "the translated protein before any", "translated protein before any further", "protein before any further processing.", "before any further processing. histone", "any further processing. histone literature", "further processing. histone literature typically", "processing. histone literature typically refers", "histone literature typically refers to", "literature typically refers to coordinates", "typically refers to coordinates of", "refers to coordinates of the", "to coordinates of the protein", "coordinates of the protein after", "of the protein after the", "the protein after the initiating", "protein after the initiating methionine", "after the initiating methionine has", "the initiating methionine has been", "initiating methionine has been removed", "has been removed therefore", "been removed therefore the", "removed therefore the coordinates", "therefore the coordinates of post", "the coordinates of post translated", "coordinates of post translated histone", "of post translated histone residues", "post translated histone 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              detection", "viruses.

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"dnase type iii", "type iii enzyme", "enzyme which", "which targets and", "targets and digests", "and digests unpaired", "digests unpaired nucleotides", "unpaired nucleotides on", "nucleotides on ssdna", "on ssdna and", "ssdna and dsdna", "and dsdna ends", "dsdna ends through", "ends through a", "through a 3'to", "a 3'to 5'", "3'to 5' exonuclease", "5' exonuclease activity", "activity perrino", "perrino fw et", "fw et al.", "et al. 1994", "1994 de", "de silva u", "silva u et", "u et al.", "et al. 2007", "2007 lehtinen", "lehtinen da et", "da et al.", "et al. 2008", "2008 fye", "fye jm et", "jm et al", "et al 2011", "al 2011 .", "2011 . trex1", ". trex1 is", "trex1 is an", "is an endoplasmic", "an endoplasmic reticulum", "reticulum er", "er associated", "protein which", "which is anchored", "is anchored to", "anchored to er", "to er membrane", "er membrane via", "membrane via the", "via the c", "the c terminal", "c terminal transmembrane", "terminal transmembrane domain", "domain 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in", "mutations in the", "in the gene", "the gene encoding", "gene encoding human", "encoding human trex1", "human trex1 are", "trex1 are associated", "are associated with", "associated with several", "with several autoimmune", "several autoimmune diseases", "diseases aicardi", "aicardi goutieres syndrome", "syndrome ags", "familial chilblain lupus", "lupus fcl", "systemic lupus erythematosus", "erythematosus sle", "that result in", "result in increased", "in increased levels", "increased levels of", "levels of interferon", "of interferon and", "interferon and circulating", "and circulating antibodies", "circulating antibodies to", "antibodies to dna", "dna crow", "crow yj et", "yj et al.", "2006 rice", "rice g et", "g et al.", "2007 lee", "lee kirsch ma", "kirsch ma et", "ma et al.", "al. 2007 .", "2007 . during", ". during infection", "during infection with", "infection with human", "with human immunodeficiency", "human immunodeficiency virus", "virus hiv", "hiv or", "or other rna", 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              detection", "dna viruses.

              detection of", "viruses.

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"tfeb to", "to the nucleus", "the nucleus thereby", "nucleus thereby controlling", "thereby controlling lysosomal", "controlling lysosomal biogenesis", "biogenesis hasan", "2012 roczniak", "roczniak ferguson a", "ferguson a et", "2012 . the", ". the authors", "the authors linked", "authors linked the", "linked the altered", "the altered lysosomal", "altered lysosomal compartment", "lysosomal compartment to", "compartment to innate", "to innate immune", "responses by suggesting", "by suggesting that", "suggesting that lysosomal", "that lysosomal biogenesis", "biogenesis regulated", "regulated by tfeb", "by tfeb and", "tfeb and mtorc1", "acted upstream of", "upstream of ifn", "of ifn independent", "ifn independent isg", "independent isg expression", "expression regulated", "regulated by irf3", "by irf3 and", "irf3 and irf7", "three prime repair exonuclease", "prime repair exonuclease 1", "exonuclease 1 trex1", "trex1 is a", "is a dnase type", "a dnase type iii", "dnase type iii enzyme", "iii enzyme which", "enzyme which targets", "which targets and digests", "targets and digests unpaired", "and digests unpaired nucleotides", "digests unpaired nucleotides on", "unpaired nucleotides on ssdna", "nucleotides on ssdna and", "on ssdna and dsdna", "ssdna and dsdna ends", "and dsdna ends through", "dsdna ends through a", "ends through a 3'to", "through a 3'to 5'", "a 3'to 5' exonuclease", "3'to 5' exonuclease activity", "exonuclease activity perrino", "activity perrino fw", "perrino fw et al.", "fw et al. 1994", "al. 1994 de", "1994 de silva", "de silva u et", "silva u et al.", "u et al. 2007", "al. 2007 lehtinen", "2007 lehtinen da", "lehtinen da et al.", "da et al. 2008", "al. 2008 fye", "2008 fye jm", "fye jm et al", "jm et al 2011", "et al 2011 .", "al 2011 . trex1", "2011 . trex1 is", ". trex1 is an", "trex1 is an endoplasmic", "is an endoplasmic reticulum", "endoplasmic reticulum er", "er associated protein", "associated protein which", "protein which is", "which is anchored to", "is anchored to er", "anchored to er membrane", "to er membrane via", "er membrane via the", "membrane via the c", "via the c terminal", "the c terminal transmembrane", "c terminal transmembrane domain", "transmembrane domain chowdhury", "domain chowdhury d", "chowdhury d et al.", "d et al. 2006", "al. 2006 richards", "2006 richards a", "richards a et al.", "a et al. 2007", "al. 2007 stetson", "2007 stetson db", "stetson db et al.", "db et al. 2009", "et al. 2009 .", "al. 2009 . trex1", "2009 . trex1 has", ". trex1 has been", "trex1 has been implicated", "has been implicated in", "been implicated in innate", "implicated in innate immune", "in innate immune responses", "innate immune responses against", "immune responses against self", "against self damaged", "self damaged or", "damaged or retrotransposons derived", "or retrotransposons derived dna", "derived dna and", "dna and retroviral", "and retroviral derived dna", "derived dna stetson", "dna stetson db", "al. 2009 yan", "2009 yan n", "yan n et al.", "n et al. 2010", "al. 2010 hasan", "2010 hasan m", "hasan m et al.", "m et al. 2012", "et al. 2012 .", "al. 2012 . trex1", "2012 . trex1 deficiency", ". trex1 deficiency in", "trex1 deficiency in human", "deficiency in human and", "in human and mouse", "human and mouse cells", "and mouse cells led", "mouse cells led to", "cells led to accumulation", "led to accumulation of", "to accumulation of cytosolic", "accumulation of cytosolic dna", "of cytosolic dna which", "cytosolic dna which resulted", "dna which resulted in", "which resulted in a", "resulted in a continual", "in a continual activation", "a continual activation of", "continual activation of cytosolic", "activation of cytosolic dna", "of cytosolic dna sensors.", "cytosolic dna sensors. in", "dna sensors. in addition", "in addition cells", "addition cells lacking", "cells lacking trex1 function", "lacking trex1 function were", "trex1 function were less", "function were less susceptible", "were less susceptible to", "less susceptible to infection", "susceptible to infection with", "to infection with different", "infection with different types", "with different types of", "different types of rna", "types of rna viruses", "rna viruses yan", "viruses yan n", "et al. 2012 .thus", "2012 .thus the", ".thus the physiological", "the physiological role of", "physiological role of the", "role of the exonuclease", "of the exonuclease trex1", "the exonuclease trex1 is", "exonuclease trex1 is to", "trex1 is to digest", "is to digest cytosolic", "to digest cytosolic host", "digest cytosolic host dna", "cytosolic host dna to", "host dna to avoid", "dna to avoid autoimmunity.", "to avoid autoimmunity. loss", "avoid autoimmunity. loss of", "autoimmunity. loss of function", "loss of function mutations", "of function mutations in", "function mutations in the", "mutations in the gene", "in the gene encoding", "the gene encoding human", "gene encoding human trex1", "encoding human trex1 are", "human trex1 are associated", "trex1 are associated with", "are associated with several", "associated with several autoimmune", "with several autoimmune diseases", "autoimmune diseases aicardi", "diseases aicardi goutieres", "goutieres syndrome ags", "ags familial", "chilblain lupus fcl", "fcl systemic", "lupus erythematosus sle", "sle that", "that result in increased", "result in increased levels", "in increased levels of", "increased levels of interferon", "levels of interferon and", "of interferon and circulating", "interferon and circulating antibodies", "and circulating antibodies to", "circulating antibodies to dna", "to dna crow", "dna crow yj", "crow yj et al.", "yj et al. 2006", "al. 2006 rice", "2006 rice g", "rice g et al.", "g et al. 2007", "al. 2007 lee", "2007 lee kirsch", "lee kirsch ma et", "kirsch ma et al.", "ma et al. 2007", "et al. 2007 .", "al. 2007 . during", "2007 . during infection", ". during infection with", "during infection with human", "infection with 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              detection", "to dna viruses.

              detection of", "dna viruses.

              detection of nucleic", "viruses.

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"authors linked the altered", "linked the altered lysosomal", "the altered lysosomal compartment", "altered lysosomal compartment to", "lysosomal compartment to innate", "compartment to innate immune", "to innate immune responses", "immune responses by suggesting", "responses by suggesting that", "by suggesting that lysosomal", "suggesting that lysosomal biogenesis", "lysosomal biogenesis regulated", "biogenesis regulated by", "regulated by tfeb and", "by tfeb and mtorc1", "mtorc1 acted", "acted upstream of ifn", "upstream of ifn independent", "of ifn independent isg", "ifn independent isg expression", "isg expression regulated", "expression regulated by", "regulated by irf3 and", "by irf3 and irf7", "irf7 hasan", "three prime repair exonuclease 1", "repair exonuclease 1 trex1", "1 trex1 is", "trex1 is a dnase", "is a dnase type iii", "a dnase type iii enzyme", "type iii enzyme which", "iii enzyme which targets", "enzyme which targets and", "which targets and digests unpaired", "targets and digests unpaired nucleotides", "and digests unpaired nucleotides on", "digests unpaired nucleotides on ssdna", "unpaired nucleotides on ssdna and", "nucleotides on ssdna and dsdna", "on ssdna and dsdna ends", "ssdna and dsdna ends through", "and dsdna ends through a", "dsdna ends through a 3'to", "ends through a 3'to 5'", "through a 3'to 5' exonuclease", "a 3'to 5' exonuclease activity", "5' exonuclease activity perrino", "exonuclease activity perrino fw", "activity perrino fw et", "perrino fw et al. 1994", "et al. 1994 de", "al. 1994 de silva", "1994 de silva u", "de silva u et al.", "silva u et al. 2007", "et al. 2007 lehtinen", "al. 2007 lehtinen da", "2007 lehtinen da et", "lehtinen da et al. 2008", "et al. 2008 fye", "al. 2008 fye jm", "2008 fye jm et", "fye jm et al 2011", "jm et al 2011 .", "et al 2011 . trex1", "al 2011 . trex1 is", "2011 . trex1 is an", ". trex1 is an endoplasmic", "trex1 is an endoplasmic reticulum", "an endoplasmic reticulum er", "reticulum er associated", "associated protein which is", "protein which is anchored", "which is anchored to er", "is anchored to er membrane", "anchored to er membrane via", "to er membrane via the", "er membrane via the c", "membrane via the c terminal", "via the c terminal transmembrane", "the c terminal transmembrane domain", "terminal transmembrane domain chowdhury", "transmembrane domain chowdhury d", "domain chowdhury d et", "chowdhury d et al. 2006", "et al. 2006 richards", "al. 2006 richards a", "2006 richards a et", "richards a et al. 2007", "et al. 2007 stetson", "al. 2007 stetson db", "2007 stetson db et", "stetson db et al. 2009", "db et al. 2009 .", "et al. 2009 . trex1", "al. 2009 . trex1 has", "2009 . trex1 has been", ". trex1 has been implicated", "trex1 has been implicated in", "has been implicated in innate", "been implicated in innate immune", "implicated in innate immune responses", "in innate immune responses against", "innate immune responses against self", "responses against self damaged", "against self damaged or", "self damaged or retrotransposons", "damaged or retrotransposons derived dna", "retrotransposons derived dna and", "derived dna and retroviral", "dna and retroviral derived", "retroviral derived dna stetson", "derived dna stetson db", "dna stetson db et", "et al. 2009 yan", "al. 2009 yan n", "2009 yan n et", "yan n et al. 2010", "et al. 2010 hasan", "al. 2010 hasan m", "2010 hasan m et", "hasan m et al. 2012", "m et al. 2012 .", "et al. 2012 . trex1", "al. 2012 . trex1 deficiency", "2012 . trex1 deficiency in", ". trex1 deficiency in human", "trex1 deficiency in human and", "deficiency in human and mouse", "in human and mouse cells", "human and mouse cells led", "and mouse cells led to", "mouse cells led to accumulation", "cells led to accumulation of", "led to accumulation of cytosolic", "to accumulation of cytosolic dna", "accumulation of cytosolic dna which", "of cytosolic dna which resulted", "cytosolic dna which resulted in", "dna which resulted in a", "which resulted in a continual", "resulted in a continual activation", "in a continual activation of", "a continual activation of cytosolic", "continual activation of cytosolic dna", "activation of cytosolic dna sensors.", "of cytosolic dna sensors. in", "cytosolic dna sensors. in addition", "sensors. in addition cells", "in addition cells lacking", "addition cells lacking trex1", "cells lacking trex1 function were", "lacking trex1 function were less", "trex1 function were less susceptible", "function were less susceptible to", "were less susceptible to infection", "less susceptible to infection with", "susceptible to infection with different", "to infection with different types", "infection with different types of", "with different types of rna", "different types of rna viruses", "of rna viruses yan", "rna viruses yan n", "viruses yan n et", "m et al. 2012 .thus", "al. 2012 .thus the", "2012 .thus the physiological", ".thus the physiological role", "the physiological role of the", "physiological role of the exonuclease", "role of the exonuclease trex1", "of the exonuclease trex1 is", "the exonuclease trex1 is to", "exonuclease trex1 is to digest", "trex1 is to digest cytosolic", "is to digest cytosolic host", "to digest cytosolic host dna", "digest cytosolic host dna to", "cytosolic host dna to avoid", "host dna to avoid autoimmunity.", "dna to avoid autoimmunity. loss", "to avoid autoimmunity. loss of", "avoid autoimmunity. loss of function", "autoimmunity. loss of function mutations", "loss of function mutations in", "of function mutations in the", "function mutations in the gene", "mutations in the gene encoding", "in the gene encoding human", "the gene encoding human trex1", "gene encoding human trex1 are", "encoding human trex1 are associated", "human trex1 are associated with", "trex1 are associated with several", "are associated with several autoimmune", "associated with several autoimmune diseases", "several autoimmune diseases aicardi", "autoimmune diseases aicardi goutieres", "diseases aicardi goutieres syndrome", "aicardi goutieres syndrome ags", "ags familial chilblain", "familial chilblain lupus fcl", "fcl systemic lupus", "systemic lupus erythematosus sle", "sle that result", "that result in increased levels", "result in increased levels of", "in increased levels of interferon", "increased levels of interferon and", "levels of interferon and circulating", "of interferon and circulating antibodies", "interferon and circulating antibodies to", "and circulating antibodies to dna", "antibodies to dna crow", "to dna crow yj", "dna crow yj et", "crow yj et al. 2006", "et al. 2006 rice", "al. 2006 rice g", "2006 rice g et", "rice g et al. 2007", "et al. 2007 lee", "al. 2007 lee kirsch", "2007 lee kirsch ma", "lee kirsch ma et al.", "kirsch ma et al. 2007", "ma et al. 2007 .", "et al. 2007 . during", "al. 2007 . during infection", "2007 . during infection with", ". during infection with human", "during infection with human immunodeficiency", "infection with human immunodeficiency virus", "human immunodeficiency virus hiv", "virus hiv or", "hiv or other rna", "other rna viruses trex1", "rna viruses trex1 activity", "viruses trex1 activity may", "trex1 activity may inhibit the", "activity may inhibit the innate", "may inhibit the innate immune", "inhibit the innate immune responses", "the innate immune responses by", "innate immune responses by processing", "immune responses by processing viral", "responses by processing viral dna", "by processing viral dna generated", "processing viral dna generated during", "viral dna generated during reverse", "dna generated during reverse transcription", "during reverse transcription yan", "reverse transcription yan n", "transcription yan n et", "et al. 2012 . it's", "al. 2012 . it's not", "2012 . it's not yet", ". it's not yet known", "it's not yet known whether", "not yet known whether trex1", "yet known whether trex1 is", "known whether trex1 is also", "whether trex1 is also involved", "trex1 is also involved in", "is also involved in regulation", "also involved in regulation of", "involved in regulation of host", "in regulation of host responses", "regulation of host responses to", "of host responses to dna", "host responses to dna viruses.

              detection", "responses to dna viruses.

              detection of", "to dna viruses.

              detection of nucleic", "dna viruses.

              detection of nucleic acids", "viruses.

              detection of nucleic acids is", "of nucleic acids is known", "nucleic acids is known to", "acids is known to launch", "is known to launch signaling", "known to launch signaling cascades", "to launch signaling cascades leading", "launch signaling cascades leading to", "signaling cascades leading to induction", "cascades leading to induction of", "leading to induction of type", "to induction of type i", "induction of type i interferons", "type i interferons which", "i interferons which in", "interferons which in turn", "which in turn orchestrate an", "in turn orchestrate an immune", "turn orchestrate an immune response", "orchestrate an immune response that", "an immune response that involves", "immune response that involves the", "response that involves the expression", "that involves the expression of", "involves the expression of hundreds", "the expression of hundreds of", "expression of hundreds of interferon", "of hundreds of interferon stimulated", "hundreds of interferon stimulated genes", "interferon stimulated genes isgs", "stimulated genes isgs .", "genes isgs . it", "isgs . it is interesting", ". it is interesting to", "it is interesting to note", "is interesting to note that", "interesting to note that interferon", "to note that interferon ifn", "that interferon ifn independent", "interferon ifn independent activation", "ifn independent activation of", "independent activation of a subset", "activation of a subset of", "of a subset of isgs", "a subset of isgs was", "subset of isgs was detected", "of isgs was detected in", "isgs was detected in mouse", "was detected in mouse and", "detected in mouse and human", "in mouse and human cells", "mouse and human cells lacking", "and human cells lacking functional", "human cells lacking functional trex1", "lacking functional trex1 hasan", "functional trex1 hasan m", "trex1 hasan m et", "al. 2012 . hasan", "2012 . hasan et", ". hasan et al.", "hasan et al. have also", "et al. have also observed", "al. have also observed that", "have also observed that trex1", "also observed that trex1 deficiency", "observed that trex1 deficiency resulted", "that trex1 deficiency resulted in", "trex1 deficiency resulted in an", "deficiency resulted in an increased", "resulted in an increased lysosomal", "in an increased lysosomal compartment.", "an increased lysosomal compartment. trex1", "increased lysosomal compartment. trex1 was", "lysosomal compartment. trex1 was found", "compartment. trex1 was found to", "trex1 was found to control", "was found to control mtorc1", "found to control mtorc1 activity", "to control mtorc1 activity in", "control mtorc1 activity in mouse", "mtorc1 activity in mouse embryonic", "activity in mouse embryonic fibroblasts", "mouse embryonic fibroblasts mef", "mef which in", "which in turn negatively regulates", "in turn negatively regulates translocation", "turn negatively regulates translocation of", "negatively regulates translocation of transcription", "regulates translocation of transcription factor", "translocation of transcription factor eb", "transcription factor eb tfeb", "eb tfeb to", "tfeb to the nucleus", "to the nucleus thereby controlling", "the nucleus thereby controlling lysosomal", "nucleus thereby controlling lysosomal biogenesis", "controlling lysosomal biogenesis hasan", "lysosomal biogenesis hasan m", "biogenesis hasan m et", "et al. 2012 roczniak", "al. 2012 roczniak ferguson", "2012 roczniak ferguson a", "roczniak ferguson a et al.", "ferguson a et al. 2012", "a et al. 2012 .", "et al. 2012 . the", "al. 2012 . the authors", "2012 . the authors linked", ". the authors linked the", "the authors linked the altered", "authors linked the altered lysosomal", "linked the altered lysosomal compartment", "the altered lysosomal compartment to", "altered lysosomal compartment to innate", "lysosomal compartment to innate immune", "compartment to innate immune responses", "to innate immune responses by", "innate immune responses by suggesting", "immune responses by suggesting that", "responses by suggesting that lysosomal", "by suggesting that lysosomal biogenesis", "that lysosomal biogenesis regulated", "lysosomal biogenesis regulated by", "biogenesis regulated by tfeb", "regulated by tfeb and mtorc1", "and mtorc1 acted", "mtorc1 acted upstream", "acted upstream of ifn independent", "upstream of ifn independent isg", "of ifn independent isg expression", "independent isg expression regulated", "isg expression regulated by", "expression regulated by irf3", "regulated by irf3 and irf7", "and irf7 hasan", "irf7 hasan m" ] }, { "record_id": "GLY_000594_1_1628", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3249367", "r hsa", "hsa 3249367", "r hsa 3249367" ] }, { "record_id": "GLY_000594_1_1628", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "stat6 mediated", "mediated induction", "induction of", "of chemokines", "stat6 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              rna", ".

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              rna", "2011 .

              rna virus", ".

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              rna", "al. 2011 .

              rna virus", "2011 .

              rna virus infection", ".

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              rna", "et al. 2011 .

              rna virus", "al. 2011 .

              rna virus infection", "2011 .

              rna virus infection triggers", ".

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              the", ".

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              the", "2013 .

              the hotspot", ".

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              the", "al. 2013 .

              the hotspot", "2013 .

              the hotspot mh2", ".

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              the", "et al. 2013 .

              the hotspot", "al. 2013 .

              the hotspot mh2", "2013 .

              the hotspot mh2 domain", ".

              the hotspot mh2 domain amino", "hotspot mh2 domain amino acid", "mh2 domain amino acid residues", "domain amino acid residues that", "amino acid residues that are", "acid residues that are targeted", "residues that are targeted by", "that are targeted by missense", "are targeted by missense mutations", "targeted by missense mutations are", "by missense mutations are asp351", "mutations are asp351 d351", "pro356 p356 and", "and arg361 r361 .", "arg361 r361 . these", "r361 . these three hotspot", ". these three hotspot residues", "these three hotspot residues map", "three hotspot residues map to", "hotspot residues map to the", "residues map to the l1", "map to the l1 loop", "to the l1 loop which", "the l1 loop which is", "l1 loop which is conserved", "loop which is conserved in", "which is conserved in smad2", "is conserved in smad2 and", "conserved in smad2 and smad3", "in smad2 and smad3 and", "smad2 and smad3 and is", "and smad3 and is involved", "smad3 and is involved in", "and is involved in intermolecular", "is involved in intermolecular interactions", "involved in intermolecular interactions that", "in intermolecular interactions that contribute", "intermolecular interactions that contribute to", "interactions that contribute to the", "that contribute to the formation", "contribute to the formation of", "to the formation of smad", "the formation of smad heterotrimers", "formation of smad heterotrimers and", "of smad heterotrimers and homotrimers", "heterotrimers and homotrimers shi", "and homotrimers shi et", "homotrimers shi et al.", "et al. 1997 fleming", "al. 1997 fleming et", "1997 fleming et al.", "fleming et al. 2013 .", "et al. 2013 . other", "al. 2013 . other frequently", "2013 . other frequently mutated", ". other frequently mutated residues", "other frequently mutated residues in", "frequently mutated residues in the", "mutated residues in the mh2", "residues in the mh2 domain", "in the mh2 domain of", "of smad4 ala406", "lys428 k428 and", "r515 are", "are involved in binding the", "involved in binding the phosphorylation", "in binding the phosphorylation motif", "the phosphorylation motif ser", "phosphorylation motif ser ser", "motif ser ser x", "ser x ser of", "x ser of smad2", "ser of smad2 and", "smad2 and smad3 with", "and smad3 with arg515", "smad3 with arg515 in", "with arg515 in the l3", "arg515 in the l3 loop", "in the l3 loop being", "the l3 loop being critical", "l3 loop being critical for", "loop being critical for this", "being critical for this interaction", "for this interaction chacko", "this interaction chacko et", "interaction chacko et al." ] }, { "record_id": "GLY_000594_1_1633", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3315487", "r hsa", "hsa 3315487", "r hsa 3315487" ] }, { "record_id": "GLY_000594_1_1633", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "smad2/3 mh2", "mh2 domain", "domain mutants", "mutants in", "in cancer", "smad2/3 mh2 domain", "mh2 domain mutants", "domain mutants in", "mutants in cancer", "smad2/3 mh2 domain mutants", "mh2 domain mutants in", "domain mutants in cancer", "smad2/3 mh2 domain mutants in", "mh2 domain mutants in cancer", "mutations in", "in the", "the mh2", "domain of", "of smad2", "smad2 and", "and smad3", "smad3 affect", "affect their", "their ability", "ability to", "to form", "form heterotrimers", "heterotrimers with", "with smad4", "thereby impairing", "impairing tgf", "tgf beta", "beta signaling", "fleming et", "et al.", "al. 2013", "2013 .

              the", ".

              the smad2", "smad3 mh2", "domain residues", "residues most", "most frequently", "frequently targeted", "targeted by", "by missense", "missense mutations", "mutations are", "are those", "those that", "that are", "are homologous", "homologous to", "to smad4", "smad4 mh2", "residues shown", "shown to", "to be", "be involved", "involved in", "the formation", "formation of", "of smad", "smad heterotrimers.", "heterotrimers. asp300", "asp300 of", "and asp258", "asp258 of", "of smad3", "smad3 correspond", "correspond to", "to the", "the frequently", "frequently mutated", "mutated asp351", "asp351 of", "of smad4.", "smad4. pro305", "pro305 of", "smad2 corresponds", "corresponds to", "mutated pro356", "pro356 of", "of smad4", "while ala354", "ala354 of", "to ala406", "ala406 of", "smad4. arg268", "arg268 of", "smad3 corresponds", "mutated arg361", "arg361 of", "smad4. smad2", "domain mutations", "mutations have", "have been", "been examined", "examined in", "in most", "most detail", "detail in", "in colorectal", "colorectal cancer", "2013 .", "mutations in the", "in the mh2", "the mh2 domain", "mh2 domain of", "domain of smad2", "of smad2 and", "smad2 and smad3", "and smad3 affect", "smad3 affect their", "affect their ability", "their ability to", "ability to form", "to form heterotrimers", "form heterotrimers with", "heterotrimers with smad4", "smad4 thereby", "thereby impairing tgf", "impairing tgf beta", "tgf beta signaling", "signaling fleming", "fleming et al.", "et al. 2013", "al. 2013 .

              the", "2013 .

              the smad2", ".

              the smad2 and", "and smad3 mh2", "smad3 mh2 domain", "mh2 domain residues", "domain residues most", "residues most frequently", "most frequently targeted", "frequently targeted by", "targeted by missense", "by missense mutations", "missense mutations are", "mutations are those", "are those that", "those that are", "that are homologous", "are homologous to", "homologous to smad4", "to smad4 mh2", "smad4 mh2 domain", "domain residues shown", "residues shown to", "shown to be", "to be involved", "be involved in", "involved in the", "in the formation", "the formation of", "formation of smad", "of smad heterotrimers.", "smad heterotrimers. asp300", "heterotrimers. asp300 of", "asp300 of smad2", "smad2 and asp258", "and asp258 of", "asp258 of smad3", "of smad3 correspond", "smad3 correspond to", "correspond to the", "to the frequently", "the frequently mutated", "frequently mutated asp351", "mutated asp351 of", "asp351 of smad4.", "of smad4. pro305", "smad4. pro305 of", "pro305 of smad2", "of smad2 corresponds", "smad2 corresponds to", "corresponds to the", "frequently mutated pro356", "mutated pro356 of", "pro356 of smad4", "smad4 while", "while ala354 of", "ala354 of smad2", "corresponds to ala406", "to ala406 of", "ala406 of smad4.", "of smad4. arg268", "smad4. arg268 of", "arg268 of smad3", "of smad3 corresponds", "smad3 corresponds to", "frequently mutated arg361", "mutated arg361 of", "arg361 of smad4.", "of smad4. smad2", "smad4. smad2 and", "mh2 domain mutations", "domain mutations have", "mutations have been", "have been examined", "been examined in", "examined in most", "in most detail", "most detail in", "detail in colorectal", "in colorectal cancer", "cancer fleming", "al. 2013 .", "mutations in the mh2", "in the mh2 domain", "the mh2 domain of", "mh2 domain of smad2", "domain of smad2 and", "of smad2 and smad3", "smad2 and smad3 affect", "and smad3 affect their", "smad3 affect their ability", "affect their ability to", "their ability to form", "ability to form heterotrimers", "to form heterotrimers with", "form heterotrimers with smad4", "with smad4 thereby", "smad4 thereby impairing", "thereby impairing tgf beta", "impairing tgf beta signaling", "beta signaling fleming", "signaling fleming et", "fleming et al. 2013", "et al. 2013 .

              the", "al. 2013 .

              the smad2", "2013 .

              the smad2 and", ".

              the smad2 and smad3", "smad2 and smad3 mh2", "and smad3 mh2 domain", "smad3 mh2 domain residues", "mh2 domain residues most", "domain residues most frequently", "residues most frequently targeted", "most frequently targeted by", "frequently targeted by missense", "targeted by missense mutations", "by missense mutations are", "missense mutations are those", "mutations are those that", "are those that are", "those that are homologous", "that are homologous to", "are homologous to smad4", "homologous to smad4 mh2", "to smad4 mh2 domain", "smad4 mh2 domain residues", "mh2 domain residues shown", "domain residues shown to", "residues shown to be", "shown to be involved", "to be involved in", "be involved in the", "involved in the formation", "in the formation of", "the formation of smad", "formation of smad heterotrimers.", "of smad heterotrimers. asp300", "smad heterotrimers. asp300 of", "heterotrimers. asp300 of smad2", "asp300 of smad2 and", "of smad2 and asp258", "smad2 and asp258 of", "and asp258 of smad3", "asp258 of smad3 correspond", "of smad3 correspond to", "smad3 correspond to the", "correspond to the frequently", "to the frequently mutated", "the frequently mutated asp351", "frequently mutated asp351 of", "mutated asp351 of smad4.", "asp351 of smad4. pro305", "of smad4. pro305 of", "smad4. pro305 of smad2", "pro305 of smad2 corresponds", "of smad2 corresponds to", "smad2 corresponds to the", "corresponds to the frequently", "the frequently mutated pro356", "frequently mutated pro356 of", "mutated pro356 of smad4", "of smad4 while", "smad4 while ala354", "while ala354 of smad2", "ala354 of smad2 corresponds", "smad2 corresponds to ala406", "corresponds to ala406 of", "to ala406 of smad4.", "ala406 of smad4. arg268", "of smad4. arg268 of", "smad4. arg268 of smad3", "arg268 of smad3 corresponds", "of smad3 corresponds to", "smad3 corresponds to the", "the frequently mutated arg361", "frequently mutated arg361 of", "mutated arg361 of smad4.", "arg361 of smad4. smad2", "of smad4. smad2 and", "smad4. smad2 and smad3", "smad3 mh2 domain mutations", "mh2 domain mutations have", "domain mutations have been", "mutations have been examined", "have been examined in", "been examined in most", "examined in most detail", "in most detail in", "most detail in colorectal", "detail in colorectal cancer", "colorectal cancer fleming", "cancer fleming et", "et al. 2013 .", "mutations in the mh2 domain", "in the mh2 domain of", "the mh2 domain of smad2", "mh2 domain of smad2 and", "domain of smad2 and smad3", "of smad2 and smad3 affect", "smad2 and smad3 affect their", "and smad3 affect their ability", "smad3 affect their ability to", "affect their ability to form", "their ability to form heterotrimers", "ability to form heterotrimers with", "to form heterotrimers with smad4", "heterotrimers with smad4 thereby", "with smad4 thereby impairing", "smad4 thereby impairing tgf", "thereby impairing tgf beta signaling", "tgf beta signaling fleming", "beta signaling fleming et", "signaling fleming et al.", "fleming et al. 2013 .

              the", "et al. 2013 .

              the smad2", "al. 2013 .

              the smad2 and", "2013 .

              the smad2 and smad3", ".

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"formation of smad heterotrimers. asp300", "of smad heterotrimers. asp300 of", "smad heterotrimers. asp300 of smad2", "heterotrimers. asp300 of smad2 and", "asp300 of smad2 and asp258", "of smad2 and asp258 of", "smad2 and asp258 of smad3", "and asp258 of smad3 correspond", "asp258 of smad3 correspond to", "of smad3 correspond to the", "smad3 correspond to the frequently", "correspond to the frequently mutated", "to the frequently mutated asp351", "the frequently mutated asp351 of", "frequently mutated asp351 of smad4.", "mutated asp351 of smad4. pro305", "asp351 of smad4. pro305 of", "of smad4. pro305 of smad2", "smad4. pro305 of smad2 corresponds", "pro305 of smad2 corresponds to", "of smad2 corresponds to the", "smad2 corresponds to the frequently", "corresponds to the frequently mutated", "to the frequently mutated pro356", "the frequently mutated pro356 of", "frequently mutated pro356 of smad4", "pro356 of smad4 while", "of smad4 while ala354", "smad4 while ala354 of", "while ala354 of smad2 corresponds", "ala354 of smad2 corresponds to", "of smad2 corresponds to ala406", "smad2 corresponds to ala406 of", "corresponds to ala406 of smad4.", "to ala406 of smad4. arg268", "ala406 of smad4. arg268 of", "of smad4. arg268 of smad3", "smad4. arg268 of smad3 corresponds", "arg268 of smad3 corresponds to", "of smad3 corresponds to the", "smad3 corresponds to the frequently", "to the frequently mutated arg361", "the frequently mutated arg361 of", "frequently mutated arg361 of smad4.", "mutated arg361 of smad4. smad2", "arg361 of smad4. smad2 and", "of smad4. smad2 and smad3", "smad4. smad2 and smad3 mh2", "and smad3 mh2 domain mutations", "smad3 mh2 domain mutations have", "mh2 domain mutations have been", "domain mutations have been examined", "mutations have been examined in", "have been examined in most", "been examined in most detail", "examined in most detail in", "in most detail in colorectal", "most detail in colorectal cancer", "in colorectal cancer fleming", "colorectal cancer fleming et", "cancer fleming et al.", "fleming et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1634", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "3359467", "r hsa", "hsa 3359467", "r hsa 3359467" ] }, { "record_id": "GLY_000594_1_1634", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective mtrr", "mtrr causes", "causes hmae", "defective mtrr causes", "mtrr causes hmae", "defective mtrr causes hmae", "defects in", "in mtrr", "mtrr cause", "cause methylcobalamin", "methylcobalamin deficiency", "deficiency type", "type e", "methionine synthase", "synthase reductase", "reductase deficiency", "wilson et", "et al.", "al. 1999", "1999 .", ". patients", "patients with", "with cble", "cble exhibit", "exhibit megaloblastic", "megaloblastic anemia", "anemia and", "and hyperhomocysteinemia.", "hyperhomocysteinemia. sam", "sam is", "is used", "used as", "as a", "a methyl", 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              sdks", "stabilization of synapses.

              sdks promotes", "of synapses.

              sdks promotes lamina", "synapses.

              sdks promotes lamina specific", "

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which undergoes post", "subunit which undergoes post transcriptional", "which undergoes post transcriptional rna", "undergoes post transcriptional rna editing", "post transcriptional rna editing that", "transcriptional rna editing that changes", "rna editing that changes glutamine", "that changes glutamine q", "glutamine q at", "q at the pore", "at the pore to arginine", "pore to arginine r", "to arginine r .", "r . incorporation of", ". incorporation of even", "incorporation of even a single", "of even a single subunit", "even a single subunit in", "a single subunit in the", "single subunit in the ampa", "subunit in the ampa receptor", "the ampa receptor confers", "ampa receptor confers ca", "receptor confers ca limiting", "confers ca limiting properties. ca", "ca limiting properties. ca permeable", "limiting properties. ca permeable ampa", "properties. ca permeable ampa receptors", "ca permeable ampa receptors permit", "permeable ampa receptors permit ca", "ampa receptors permit ca and", "receptors permit ca and na", "permit ca and na whereas", "ca and na whereas ca", "and na whereas ca impermeable", "na whereas ca impermeable ampa", "whereas ca impermeable ampa receptors", "ca impermeable ampa receptors permit", "impermeable ampa receptors permit only", "ampa receptors permit only na.", "receptors permit only na. in", "permit only na. in general", "na. in general glutamatergic", "in general glutamatergic neurons", "general glutamatergic neurons contain", "glutamatergic neurons contain ca impermeable", "neurons contain ca impermeable ampa", "contain ca impermeable ampa receptors", "ca impermeable ampa receptors and", "impermeable ampa receptors and gabaergic", "ampa receptors and gabaergic interneurons", "receptors and gabaergic interneurons contain", "and gabaergic interneurons contain ca", "gabaergic interneurons contain ca permeable", "interneurons contain ca permeable ampa", "contain ca permeable ampa receptors.", "permeable ampa receptors. however", "receptors. however some", "however some synapses do", "some synapses do contain a", "synapses do contain a mixture", "do contain a mixture of", "contain a mixture of ca", "a mixture of ca permeable", "mixture of ca permeable and", "of ca permeable and ca", "ca permeable and ca impermeable", "permeable and ca impermeable ampa", "and ca impermeable ampa receptors.", "ca impermeable ampa receptors. glur1", "impermeable ampa receptors. glur1 4", "ampa receptors. glur1 4 are", "receptors. glur1 4 are encoded", "glur1 4 are encoded by", "4 are encoded by four", "are encoded by four genes", "encoded by four genes however", "four genes however alternative", "genes however alternative splicing", "however alternative splicing generates", "alternative splicing generates several functional", "splicing generates several functional subunits", "generates several functional subunits namely", "several functional subunits namely long", "functional subunits namely long and", "subunits namely long and short", "namely long and short forms", "long and short forms of", "and short forms of glur1", "short forms of glur1 and", "forms of glur1 and glur2.", "of glur1 and glur2. glur4", "glur1 and glur2. glur4 has", "and glur2. glur4 has long", "glur2. glur4 has long tail", "glur4 has long tail only", "has long tail only and", "long tail only and glur3", "tail only and glur3 has", "only and glur3 has short", "and glur3 has short tail", "glur3 has short tail only.", "has short tail only. besides", "short tail only. besides the", "tail only. besides the differences", "only. besides the differences in", "besides the differences in the", "the differences in the tail", "differences in the tail length", "the tail length flip/flop", "tail length flip/flop isoforms", "length flip/flop isoforms are", "flip/flop isoforms are generated by", "isoforms are generated by an", "are generated by an interchangeable", "generated by an interchangeable exon", "by an interchangeable exon that", "an interchangeable exon that codes", "interchangeable exon that codes the", "exon that codes the fourth", "that codes the fourth membranous", "codes the fourth membranous domain", "the fourth membranous domain towards", "fourth membranous domain towards the", "membranous domain towards the c", "domain towards the c terminus.", "towards the c terminus. the", "the c terminus. the fip/flop", "c terminus. the fip/flop isoforms", "terminus. the fip/flop isoforms determine", "the fip/flop isoforms determine rate", "fip/flop isoforms determine rate of", "isoforms determine rate of desensitization/resensitization", "determine rate of desensitization/resensitization and", "rate of desensitization/resensitization and the", "of desensitization/resensitization and the rate", "desensitization/resensitization and the rate of", "and the rate of channel", "the rate of channel closing.", "rate of channel closing. receptors", "of channel closing. receptors homomers", "channel closing. receptors homomers or", "closing. receptors homomers or heteromers", "receptors homomers or heteromers assembled", "homomers or heteromers assembled from", "or heteromers assembled from the", "heteromers assembled from the combination", "assembled from the combination of", "from the combination of glur1", "the combination of glur1 4", "combination of glur1 4 subunits", "of glur1 4 subunits that", "glur1 4 subunits that vary", "4 subunits that vary in", "subunits that vary in c", "that vary in c tail", "vary in c tail length", "in c tail length and", "c tail length and flip/flop", "tail length and flip/flop versions", "length and flip/flop versions generates", "and flip/flop versions generates a", "flip/flop versions generates a whole", "versions generates a whole battery", "generates a whole battery of", "a whole battery of functionally", "whole battery of functionally distinct", "battery of functionally distinct ampa", "of functionally distinct ampa receptors." ] }, { "record_id": "GLY_000594_1_1649", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4043916", "r hsa", "hsa 4043916", "r hsa 4043916" ] }, { "record_id": "GLY_000594_1_1649", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective mpi", "mpi causes", "causes mpi", "mpi cdg", "defective mpi causes", "mpi causes mpi", "causes mpi cdg", "defective mpi causes mpi", "mpi causes mpi cdg", "defective mpi causes mpi cdg", "mannose 6", "6 phosphate", "phosphate isomerase", "normally isomerises", "isomerises fructose", "fructose 6", "to mannose", "in the", "the cytosol.", "cytosol. man6p", "man6p is", "is a", "a precursor", "precursor in", "the synthesis", "synthesis of", "of gdp", "gdp mannose", "mannose and", "and dolichol", "dolichol phosphate", "phosphate mannose", "required for", "for mannosyl", "mannosyl transfer", "transfer reactions", "reactions in", "the n", "n glycosylation", "glycosylation of", "of proteins.", "proteins. defects", "defects in", "in mpi", "mpi cause", "cause congenital", "congenital disorder", "disorder of", "of glycosylation", "glycosylation 1b", "previously known", "known as", "as cdg1b", "a multisystem", "multisystem disorder", "disorder characterised", "characterised by", "by under", "under glycosylated", "glycosylated serum", "serum glycoproteins", "schollen et", "et al.", "al. 2000", "2000 .", ". unlike", "unlike pmm2", "pmm2 cdg", "there is", "is no", "no neurological", "neurological involvement", "involvement with", "with mpi", "mpi cdg.", "cdg. instead", "patients present", "present predominantly", "predominantly with", "with diarrhoea", "failure to", "to thrive", "thrive and", "and protein", "protein losing", "losing enteropathy", "pelletier et", "al. 1986", "1986 .", ". mpi", "cdg is", "is one", "one of", "of two", "two cdgs", "cdgs that", "that can", "can be", "be treated", "treated with", "with oral", "oral mannose", "mannose supplementation", "but can", "be fatal", "fatal if", "if left", "left untreated", "marquardt &", "& denecke", "denecke 2003", "2003 .", "mannose 6 phosphate", "6 phosphate isomerase", "isomerase mpi", "mpi normally", "normally isomerises fructose", "isomerises fructose 6", "fructose 6 phosphate", "phosphate fru6p", "fru6p to", "to mannose 6", "phosphate man6p", "man6p in", "in the cytosol.", "the cytosol. man6p", "cytosol. man6p is", "man6p is a", "is a precursor", "a precursor in", "precursor in the", "in the synthesis", "the synthesis of", "synthesis of gdp", "of gdp mannose", "gdp mannose and", "mannose and dolichol", "and dolichol phosphate", "dolichol phosphate mannose", "mannose required", "required for mannosyl", "for mannosyl transfer", "mannosyl transfer reactions", "transfer reactions in", "reactions in the", "in the n", "the n glycosylation", "n glycosylation of", "glycosylation of proteins.", "of proteins. defects", "proteins. defects in", "defects in mpi", "in mpi cause", "mpi cause congenital", "cause congenital 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serum glycoproteins", "serum glycoproteins schollen", "glycoproteins schollen et", "schollen et al. 2000", "et al. 2000 .", "al. 2000 . unlike", "2000 . unlike pmm2", ". unlike pmm2 cdg", "pmm2 cdg cdg1a", "cdg1a there", "there is no neurological", "is no neurological involvement", "no neurological involvement with", "neurological involvement with mpi", "involvement with mpi cdg.", "with mpi cdg. instead", "cdg. instead patients", "instead patients present", "patients present predominantly with", "present predominantly with diarrhoea", "with diarrhoea failure", "diarrhoea failure to", "failure to thrive and", "to thrive and protein", "thrive and protein losing", "and protein losing enteropathy", "losing enteropathy pelletier", "enteropathy pelletier et", "pelletier et al. 1986", "et al. 1986 .", "al. 1986 . mpi", "1986 . mpi cdg", ". mpi cdg is", "mpi cdg is one", "cdg is one of", "is one of two", "one of two cdgs", "of two cdgs that", "two cdgs that can", "cdgs that can be", "that can be treated", "can be treated with", "be treated with oral", "treated with oral mannose", "with oral mannose supplementation", "mannose supplementation but", "supplementation but can", "but can be fatal", "can be fatal if", "be fatal if left", "fatal if left untreated", "left untreated marquardt", "untreated marquardt &", "marquardt & denecke 2003", "& denecke 2003 .", "6 phosphate isomerase mpi", "isomerase mpi normally", "mpi normally isomerises fructose", "normally isomerises fructose 6 phosphate", "fructose 6 phosphate fru6p", "phosphate fru6p to", "fru6p to mannose 6", "mannose 6 phosphate man6p", "phosphate man6p in", "man6p in the cytosol.", "in the cytosol. man6p is", "the cytosol. man6p is a", "cytosol. man6p is a precursor", "man6p is a precursor in", "is a precursor in the", "a precursor in the synthesis", "precursor in the synthesis of", "in the synthesis of gdp", "the synthesis of gdp mannose", "synthesis of gdp mannose and", "of gdp mannose and dolichol", "gdp mannose and dolichol phosphate", "mannose and dolichol phosphate mannose", "dolichol phosphate mannose required", "phosphate mannose required for", "mannose required for mannosyl", "required for mannosyl transfer reactions", "for mannosyl transfer reactions in", "mannosyl transfer reactions in the", "transfer reactions in the n", "reactions in the n glycosylation", "in the n glycosylation of", "the n glycosylation of proteins.", "n glycosylation of proteins. defects", "glycosylation of proteins. defects in", "of proteins. defects in mpi", "proteins. defects in mpi cause", "defects in mpi cause congenital", "in mpi cause congenital disorder", "mpi cause congenital disorder of", "cause congenital disorder of glycosylation", "congenital disorder of glycosylation 1b", "of glycosylation 1b mpi", "glycosylation 1b mpi cdg", "mpi cdg previously known", "cdg previously known as", "as cdg1b mim:602579", "mim:602579 a multisystem", "602579 a multisystem", "a multisystem disorder characterised by", "multisystem disorder characterised by under", "disorder characterised by under glycosylated", "characterised by under glycosylated serum", "by under glycosylated serum glycoproteins", "glycosylated serum glycoproteins schollen", "serum glycoproteins schollen et", "glycoproteins schollen et al.", "schollen et al. 2000 .", "et al. 2000 . unlike", "al. 2000 . unlike pmm2", "2000 . unlike pmm2 cdg", "unlike pmm2 cdg cdg1a", "cdg1a there is", "there is no neurological involvement", "is no neurological involvement with", "no neurological involvement with mpi", "neurological involvement with mpi cdg.", "involvement with mpi cdg. instead", "mpi cdg. instead patients", "cdg. instead patients present", "instead patients present predominantly", "patients present predominantly with diarrhoea", "predominantly with diarrhoea failure", "with diarrhoea failure to", "diarrhoea failure to thrive", "failure to thrive and protein", "to thrive and protein losing", "thrive and protein losing enteropathy", "protein losing enteropathy pelletier", "losing enteropathy pelletier et", "enteropathy pelletier et al.", "pelletier et al. 1986 .", "et al. 1986 . mpi", "al. 1986 . mpi cdg", "1986 . mpi cdg is", ". mpi cdg is one", "mpi cdg is one of", "cdg is one of two", "is one of two cdgs", "one of two cdgs that", "of two cdgs that can", "two cdgs that can be", "cdgs that can be treated", "that can be treated with", "can be treated with oral", "be treated with oral mannose", "treated with oral mannose supplementation", "oral mannose supplementation but", "mannose supplementation but can", "supplementation but can be", "but can be fatal if", "can be fatal if left", "be fatal if left untreated", "if left untreated marquardt", "left untreated marquardt &", "untreated marquardt & denecke", "marquardt & denecke 2003 ." ] }, { "record_id": "GLY_000594_1_1650", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4085011", "r hsa", "hsa 4085011", "r hsa 4085011" ] }, { "record_id": "GLY_000594_1_1650", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gne", "gne causes", "causes sialuria", "nk and", "and ibm2", "defective gne causes", "gne causes sialuria", "sialuria nk", "nk and ibm2", "defective gne causes sialuria", "causes sialuria nk", "sialuria nk and", "gne causes sialuria nk", "causes sialuria nk and", "sialuria nk and ibm2", "is caused", "caused by", "by a", "a metabolic", "metabolic defect", "defect where", "where the", "the udp?n?acetylglucosamine", "udp?n?acetylglucosamine 2?epimerase", "n?acetylmannosamine kinase", "gene lacks", "lacks feedback", "feedback inhibition", "inhibition resulting", "resulting in", "in constitutive", "constitutive overproduction", "overproduction of", "of free", "free sialic", "sialic acid", "montreuil et", "et al.", "al. 1968", "fontaine et", "1968 .", ". sialuria", "sialuria is", "is characterised", "characterised by", "a large", "large cytoplasmic", "cytoplasmic accumulation", "accumulation and", "and urinary", "urinary excretion", "excretion of", "of neu5ac", "kamerling et", "al. 1979", "1979 .", ". sialurias", "sialurias differ", "differ from", "from sialidoses", "in which", "which there", "there is", "is storage", "storage and", "and excretion", "of 'bound'", "'bound' neu5ac.", "neu5ac. defects", "defects in", "in gne", "gne also", "also cause", "cause nonaka", "nonaka myopathy", "an early", "early adult", "adult onset", "onset disorder", "disorder characterised", "by muscle", "muscle weakness", "weakness and", "and wasting", "wasting of", "of distal", "distal muscles", "especially the", "the anterior", "anterior tibial", "tibial muscles", "nonaka et", "al. 1981", "asaka et", "al. 2001", "2001 .", ". defects", "cause inclusion", "inclusion body", "body myopathy", "myopathy 2", "an autosomal", "autosomal recessive", "recessive disorder", "disorder with", "with a", "a similar", "similar phenotype", "phenotype to", "to nonaka", "nk .", ". ibm2", "ibm2 is", "is an", "an adult", "proximal and", "and distal", "distal muscle", "wasting disorder.", "disorder. muscle", "muscle biospsy", "biospsy reveals", "reveals from", "from sufferers", "sufferers shows", "shows a", "a rimmed", "rimmed vacuole", "vacuole myopathy", "myopathy and", "and the", "the degenerating", "degenerating muscle", "muscle fibers", "fibers contained", "contained abnormal", "abnormal amounts", "amounts of", "of beta", "beta amyloid", "amyloid protein", "protein such", "such as", "as that", "that found", "found in", "in neurodegenerative", "neurodegenerative diorders.", "diorders. however", "is no", "no neurological", "neurological symptoms", "symptoms in", "in these", "these patients", "argov &", "& yarom", "yarom 1984", "1984 .", "sialuria mim:269921", "mim:269921 is", "269921 is", "is caused by", "caused by a", "by a metabolic", "a metabolic defect", "metabolic defect where", "defect where the", "where the udp?n?acetylglucosamine", "the udp?n?acetylglucosamine 2?epimerase", "2?epimerase n?acetylmannosamine", "kinase gne", "gne gene", "gene lacks feedback", "lacks feedback inhibition", "feedback inhibition resulting", "inhibition resulting in", "resulting in constitutive", "in constitutive overproduction", "constitutive overproduction of", "overproduction of free", "of free sialic", "free sialic acid", "acid neu5ac", "montreuil et al.", "et al. 1968", "1968 fontaine", "fontaine et al.", "al. 1968 .", "1968 . sialuria", ". sialuria is", "sialuria is characterised", "is characterised by", "characterised by a", "by a large", "a large cytoplasmic", "large cytoplasmic accumulation", "cytoplasmic accumulation and", "accumulation and urinary", "and urinary excretion", "urinary excretion of", "excretion of neu5ac", "neu5ac kamerling", "kamerling et al.", "et al. 1979", "al. 1979 .", "1979 . sialurias", ". sialurias differ", "sialurias differ from", "differ from sialidoses", "sialidoses in", "in which there", "which there is", "there is storage", "is storage and", "storage and excretion", "and excretion of", "excretion of 'bound'", "of 'bound' neu5ac.", "'bound' neu5ac. defects", "neu5ac. defects in", "defects in gne", "in gne also", "gne also cause", "also cause nonaka", "cause nonaka myopathy", "myopathy nk", "nk mim:605820", "an early adult", "early adult onset", "adult onset disorder", "onset disorder characterised", "disorder characterised by", "characterised by muscle", "by muscle weakness", "muscle weakness and", "weakness and wasting", "and wasting of", "wasting of distal", "of distal muscles", "muscles especially", "especially the anterior", "the anterior tibial", "anterior tibial muscles", "muscles nonaka", "nonaka et al.", "et al. 1981", "1981 asaka", "asaka et al.", "et al. 2001", "al. 2001 .", "2001 . defects", ". defects in", "also cause inclusion", "cause inclusion body", "inclusion body myopathy", "body myopathy 2", "2 ibm2", "ibm2 mim:600737", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder with", "disorder with a", "with a similar", "a similar phenotype", "similar phenotype to", "phenotype to nonaka", "to nonaka myopathy", "nk . ibm2", ". ibm2 is", "ibm2 is an", "is an adult", "an adult onset", "onset proximal", "proximal and distal", "and distal muscle", "distal muscle weakness", "and wasting disorder.", "wasting disorder. muscle", "disorder. muscle biospsy", "muscle biospsy reveals", "biospsy reveals from", "reveals from sufferers", "from sufferers shows", "sufferers shows a", "shows a rimmed", "a rimmed vacuole", "rimmed vacuole myopathy", "vacuole myopathy and", "myopathy and the", "and the degenerating", "the degenerating muscle", "degenerating muscle fibers", "muscle fibers contained", "fibers contained abnormal", "contained abnormal amounts", "abnormal amounts of", "amounts of beta", "of beta amyloid", "beta amyloid protein", "amyloid protein such", "protein such as", "such as that", "as that found", "that found in", "found in neurodegenerative", "in neurodegenerative diorders.", "neurodegenerative diorders. however", "however there", "there is no", "is no neurological", "no neurological symptoms", "neurological symptoms in", "symptoms in these", "in these patients", "patients argov", "argov & yarom", "& yarom 1984", "yarom 1984 .", "mim:269921 is caused", "269921 is caused", "is caused by a", "caused by a metabolic", "by a metabolic defect", "a metabolic defect where", "metabolic defect where the", "defect where the udp?n?acetylglucosamine", "where the udp?n?acetylglucosamine 2?epimerase", "udp?n?acetylglucosamine 2?epimerase n?acetylmannosamine", "2?epimerase n?acetylmannosamine kinase", "n?acetylmannosamine kinase gne", "gne gene lacks", "gene lacks feedback inhibition", "lacks feedback inhibition resulting", "feedback inhibition resulting in", "inhibition resulting in constitutive", "resulting in constitutive overproduction", "in constitutive overproduction of", "constitutive overproduction of free", "overproduction of free sialic", "of free sialic acid", "sialic acid neu5ac", "neu5ac montreuil", "montreuil et al. 1968", "al. 1968 fontaine", "1968 fontaine et", "fontaine et al. 1968", "et al. 1968 .", "al. 1968 . sialuria", "1968 . sialuria is", ". sialuria is characterised", "sialuria is characterised by", "is characterised by a", "characterised by a large", "by a large cytoplasmic", "a large cytoplasmic accumulation", "large cytoplasmic accumulation and", "cytoplasmic accumulation and urinary", "accumulation and urinary excretion", "and urinary excretion of", "urinary excretion of neu5ac", "of neu5ac kamerling", "neu5ac kamerling et", "kamerling et al. 1979", "et al. 1979 .", "al. 1979 . sialurias", "1979 . sialurias differ", ". sialurias differ from", "sialurias differ from sialidoses", "from sialidoses in", "sialidoses in which", "in which there is", "which there is storage", "there is storage and", "is storage and excretion", "storage and excretion of", "and excretion of 'bound'", "excretion of 'bound' neu5ac.", "of 'bound' neu5ac. defects", "'bound' neu5ac. defects in", "neu5ac. defects in gne", "defects in gne also", "in gne also cause", "gne also cause nonaka", "also cause nonaka myopathy", "nonaka myopathy nk", "mim:605820 an", "605820 an", "an early adult onset", "early adult onset disorder", "adult onset disorder characterised", "onset disorder characterised by", "disorder characterised by muscle", "characterised by muscle weakness", "by muscle weakness and", "muscle weakness and wasting", "weakness and wasting of", "and wasting of distal", "wasting of distal muscles", "distal muscles especially", "muscles especially the", "especially the anterior tibial", "the anterior tibial muscles", "tibial muscles nonaka", "muscles nonaka et", "nonaka et al. 1981", "al. 1981 asaka", "1981 asaka et", "asaka et al. 2001", "et al. 2001 .", "al. 2001 . defects", "2001 . defects in", ". defects in gne", "gne also cause inclusion", "also cause inclusion body", "cause inclusion body myopathy", "inclusion body myopathy 2", "myopathy 2 ibm2", "mim:600737 an", "600737 an", "an autosomal recessive disorder", "autosomal recessive disorder with", "recessive disorder with a", "disorder with a similar", "with a similar phenotype", "a similar phenotype to", "similar phenotype to nonaka", "phenotype to nonaka myopathy", "myopathy nk .", "nk . ibm2 is", ". ibm2 is an", "ibm2 is an adult", "is an adult onset", "adult onset proximal", "onset proximal and", "proximal and distal muscle", "and distal muscle weakness", "distal muscle weakness and", "weakness and wasting disorder.", "and wasting disorder. muscle", "wasting disorder. muscle biospsy", "disorder. muscle biospsy reveals", "muscle biospsy reveals from", "biospsy reveals from sufferers", "reveals from sufferers shows", "from sufferers shows a", "sufferers shows a rimmed", "shows a rimmed vacuole", "a rimmed vacuole myopathy", "rimmed vacuole myopathy and", "vacuole myopathy and the", "myopathy and the degenerating", "and the degenerating muscle", "the degenerating muscle fibers", "degenerating muscle fibers contained", "muscle fibers contained abnormal", "fibers contained abnormal amounts", "contained abnormal amounts of", "abnormal amounts of beta", "amounts of beta amyloid", "of beta amyloid protein", "beta amyloid protein such", "amyloid protein such as", "protein such as that", "such as that found", "as that found in", "that found in neurodegenerative", "found in neurodegenerative diorders.", "in neurodegenerative diorders. however", "diorders. however there", "however there is", "there is no neurological", "is no neurological symptoms", "no neurological symptoms in", "neurological symptoms in these", "symptoms in these patients", "these patients argov", "patients argov &", "argov & yarom 1984", "& yarom 1984 .", "sialuria mim:269921 is", "mim:269921 is caused by", "269921 is caused by", "is caused by a metabolic", "caused by a metabolic defect", "by a metabolic defect where", "a metabolic defect where the", "metabolic defect where the udp?n?acetylglucosamine", "defect where the udp?n?acetylglucosamine 2?epimerase", "the udp?n?acetylglucosamine 2?epimerase n?acetylmannosamine", "udp?n?acetylglucosamine 2?epimerase n?acetylmannosamine kinase", "kinase gne gene", "gne gene lacks feedback", "gene lacks feedback inhibition resulting", "lacks feedback inhibition resulting in", "feedback inhibition resulting in constitutive", "inhibition resulting in constitutive overproduction", "resulting in constitutive overproduction of", "in constitutive overproduction of free", "constitutive overproduction of free sialic", "overproduction of free sialic acid", "free sialic acid neu5ac", "neu5ac montreuil et", "et al. 1968 fontaine", "al. 1968 fontaine et", "1968 fontaine et al.", "fontaine et al. 1968 .", "et al. 1968 . sialuria", "al. 1968 . sialuria is", "1968 . sialuria is characterised", ". sialuria is characterised by", "sialuria is characterised by a", "is characterised by a large", "characterised by a large cytoplasmic", "by a large cytoplasmic accumulation", "a large cytoplasmic accumulation and", "large cytoplasmic accumulation and urinary", "cytoplasmic accumulation and urinary excretion", "accumulation and urinary excretion of", "and urinary excretion of neu5ac", "excretion of neu5ac kamerling", "of neu5ac kamerling et", "neu5ac kamerling et al.", "kamerling et al. 1979 .", "et al. 1979 . sialurias", "al. 1979 . sialurias differ", "1979 . sialurias differ from", ". sialurias differ from sialidoses", "differ from sialidoses in", "from sialidoses in which", "sialidoses in which there", "in which there is storage", "which there is storage and", "there is storage and excretion", "is storage and excretion of", "storage and excretion of 'bound'", "and excretion of 'bound' neu5ac.", "excretion of 'bound' neu5ac. defects", "of 'bound' neu5ac. defects in", "'bound' neu5ac. defects in gne", "neu5ac. defects in gne also", "defects in gne also cause", "in gne also cause nonaka", "gne also cause nonaka myopathy", "cause nonaka myopathy nk", "myopathy nk mim:605820", "mim:605820 an early", "605820 an early", "an early adult onset disorder", "early adult onset disorder characterised", "adult onset disorder characterised by", "onset disorder characterised by muscle", "disorder characterised by muscle weakness", "characterised by muscle weakness and", "by muscle weakness and wasting", "muscle weakness and wasting of", "weakness and wasting of distal", "and wasting of distal muscles", "of distal muscles especially", "distal muscles especially the", "muscles especially the anterior", "especially the anterior tibial muscles", "anterior tibial muscles nonaka", "tibial muscles nonaka et", "muscles nonaka et al.", "et al. 1981 asaka", "al. 1981 asaka et", "1981 asaka et al.", "asaka et al. 2001 .", "et al. 2001 . defects", "al. 2001 . defects in", "2001 . defects in gne", ". defects in gne also", "in gne also cause inclusion", "gne also cause inclusion body", "also cause inclusion body myopathy", "cause inclusion body myopathy 2", "body myopathy 2 ibm2", "2 ibm2 mim:600737", "mim:600737 an autosomal", "600737 an autosomal", "an autosomal recessive disorder with", "autosomal recessive disorder with a", "recessive disorder with a similar", "disorder with a similar phenotype", "with a similar phenotype to", "a similar phenotype to nonaka", "similar phenotype to nonaka myopathy", "to nonaka myopathy nk", "nonaka myopathy nk .", "myopathy nk . ibm2", "nk . ibm2 is an", ". ibm2 is an adult", "ibm2 is an adult onset", "an adult onset proximal", "adult onset proximal and", "onset proximal and distal", "proximal and distal muscle weakness", "and distal muscle weakness and", "distal muscle weakness and wasting", "muscle weakness and wasting disorder.", "weakness and wasting disorder. muscle", "and wasting disorder. muscle biospsy", "wasting disorder. muscle biospsy reveals", "disorder. muscle biospsy reveals from", "muscle biospsy reveals from sufferers", "biospsy reveals from sufferers shows", "reveals from sufferers shows a", "from sufferers shows a rimmed", "sufferers shows a rimmed vacuole", "shows a rimmed vacuole myopathy", "a rimmed vacuole myopathy and", "rimmed vacuole myopathy and the", "vacuole myopathy and the degenerating", "myopathy and the degenerating muscle", "and the degenerating muscle fibers", "the degenerating muscle fibers contained", "degenerating muscle fibers contained abnormal", "muscle fibers contained abnormal amounts", "fibers contained abnormal amounts of", "contained abnormal amounts of beta", "abnormal amounts of beta amyloid", "amounts of beta amyloid protein", "of beta amyloid protein such", "beta amyloid protein such as", "amyloid protein such as that", "protein such as that found", "such as that found in", "as that found in neurodegenerative", "that found in neurodegenerative diorders.", "found in neurodegenerative diorders. however", "neurodegenerative diorders. however there", "diorders. however there is", "however there is no", "there is no neurological symptoms", "is no neurological symptoms in", "no neurological symptoms in these", "neurological symptoms in these patients", "in these patients argov", "these patients argov &", "patients argov & yarom", "argov & yarom 1984 ." ] }, { "record_id": "GLY_000594_1_1651", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4085023", "r hsa", "hsa 4085023", "r hsa 4085023" ] }, { "record_id": "GLY_000594_1_1651", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gfpt1", "gfpt1 causes", "causes cmsta1", "defective gfpt1 causes", "gfpt1 causes cmsta1", "defective gfpt1 causes cmsta1", "glucosamine fructose", "fructose 6", "6 phosphate", "phosphate aminotransferases", "aminotransferases 1", "1 and", "and 2", "gfpt1 2", "are the", "the first", "first and", "and rate", "rate limiting", "limiting enzymes", "enzymes in", "in the", "the hexosamine", "hexosamine synthesis", "synthesis pathway", "and thus", "thus formation", "formation of", "of hexosamines", "hexosamines like", "like n", "n acetylglucosamine", "glcnac .", ". these", "these enzymes", "enzymes probably", "probably play", "play a", "a role", "role in", "in limiting", "limiting the", "the availability", "availability of", "of substrates", "substrates for", "for the", "the n", "and o", "o linked", "linked glycosylation", "glycosylation of", "of proteins.", "proteins. gfpt1", "gfpt1 and", "2 are", "are required", "required for", "for normal", "normal functioning", "functioning of", "of neuromuscular", "neuromuscular synaptic", "synaptic transmission.", "transmission. defects", "defects in", "in gfpt1", "gfpt1 lead", "lead to", "to myasthenia", "with tubular", "tubular aggregates", "aggregates 1", "characterised by", "by altered", "altered muscle", "muscle fibre", "fibre morphology", "morphology and", "and impaired", "impaired neuromuscular", "neuromuscular junction", "junction development.", "development. sufferers", "sufferers of", "of cmsta1", "cmsta1 show", "show a", "a good", "good response", "response to", "to acetylcholinesterase", "acetylcholinesterase inhibitors", "senderek et", "et al.", "al. 2011", "2011 .", ". the", "the missense", "missense mutations", "mutations observed", "observed do", "do not", "not always", "always result", "result in", "in significant", "significant reduction", "reduction in", "in enzyme", "enzyme activity", "but biopsies", "biopsies show", "show reduced", "reduced amounts", "amounts of", "of gfpt1", "gfpt1 protein", "protein suggesting", "suggesting increased", "increased turnover", "turnover or", "or defective", "defective translation", "glucosamine fructose 6", "fructose 6 phosphate", "6 phosphate aminotransferases", "phosphate aminotransferases 1", "aminotransferases 1 and", "1 and 2", "2 gfpt1", "are the first", "the first and", "first and rate", "and rate limiting", "rate limiting enzymes", "limiting enzymes in", "enzymes in the", "in the hexosamine", "the hexosamine synthesis", "hexosamine synthesis pathway", "pathway and", "and thus formation", "thus formation of", "formation of hexosamines", "of hexosamines like", "hexosamines like n", "like n acetylglucosamine", "acetylglucosamine glcnac", "glcnac . these", ". these enzymes", "these enzymes probably", "enzymes probably play", "probably play a", "play a role", "a role in", "role in limiting", "in limiting the", "limiting the availability", "the availability of", "availability of substrates", "of substrates for", "substrates for the", "for the n", "n and", "and o linked", "o linked glycosylation", "linked glycosylation of", "glycosylation of proteins.", "of proteins. gfpt1", "proteins. gfpt1 and", "gfpt1 and 2", "and 2 are", "2 are required", "are required for", "required for normal", "for normal functioning", "normal functioning of", "functioning of neuromuscular", "of neuromuscular synaptic", "neuromuscular synaptic transmission.", "synaptic transmission. defects", "transmission. defects in", "defects in gfpt1", "in gfpt1 lead", "gfpt1 lead to", "lead to myasthenia", "myasthenia congenital", "congenital with", "with tubular aggregates", "tubular aggregates 1", "1 cmsta1", "cmsta1 mim:610542", "characterised by altered", "by altered muscle", "altered muscle fibre", "muscle fibre morphology", "fibre morphology and", "morphology and impaired", "and impaired neuromuscular", "impaired neuromuscular junction", "neuromuscular junction development.", "junction development. sufferers", "development. sufferers of", "sufferers of cmsta1", "of cmsta1 show", "cmsta1 show a", "show a good", "a good response", "good response to", "response to acetylcholinesterase", "to acetylcholinesterase inhibitors", "inhibitors senderek", "senderek et al.", "et al. 2011", "al. 2011 .", "2011 . the", ". the missense", "the missense mutations", "missense mutations observed", "mutations observed do", "observed do not", "do not always", "not always result", "always result in", "result in significant", "in significant reduction", "significant reduction in", "reduction in enzyme", "in enzyme activity", "activity but", "but biopsies show", "biopsies show reduced", "show reduced amounts", "reduced amounts of", "amounts of gfpt1", "of gfpt1 protein", "gfpt1 protein suggesting", "protein suggesting increased", "suggesting increased turnover", "increased turnover or", "turnover or defective", "or defective translation", "translation senderek", "glucosamine fructose 6 phosphate", "fructose 6 phosphate aminotransferases", "6 phosphate aminotransferases 1", "phosphate aminotransferases 1 and", "aminotransferases 1 and 2", "and 2 gfpt1", "2 gfpt1 2", "gfpt1 2 are", "2 are the", "are the first and", "the first and rate", "first and rate limiting", "and rate limiting enzymes", "rate limiting enzymes in", "limiting enzymes in the", "enzymes in the hexosamine", "in the hexosamine synthesis", "the hexosamine synthesis pathway", "synthesis pathway and", "pathway and thus", "and thus formation of", "thus formation of hexosamines", "formation of hexosamines like", "of hexosamines like n", "hexosamines like n acetylglucosamine", "n acetylglucosamine glcnac", "acetylglucosamine glcnac .", "glcnac . these enzymes", ". these enzymes probably", "these enzymes probably play", "enzymes probably play a", "probably play a role", "play a role in", "a role in limiting", "role in limiting the", "in limiting the availability", "limiting the availability of", "the availability of substrates", "availability of substrates for", "of substrates for the", "substrates for the n", "the n and", "n and o", "and o linked glycosylation", "o linked glycosylation of", "linked glycosylation of proteins.", "glycosylation of proteins. gfpt1", "of proteins. gfpt1 and", "proteins. gfpt1 and 2", "gfpt1 and 2 are", "and 2 are required", "2 are required for", "are required for normal", "required for normal functioning", "for normal functioning of", "normal functioning of neuromuscular", "functioning of neuromuscular synaptic", "of neuromuscular synaptic transmission.", "neuromuscular synaptic transmission. defects", "synaptic transmission. defects in", "transmission. defects in gfpt1", "defects in gfpt1 lead", "in gfpt1 lead to", "gfpt1 lead to myasthenia", "to myasthenia congenital", "congenital with tubular", "with tubular aggregates 1", "aggregates 1 cmsta1", "mim:610542 characterised", "610542 characterised", "characterised by altered muscle", "by altered muscle fibre", "altered muscle fibre morphology", "muscle fibre morphology and", "fibre morphology and impaired", "morphology and impaired neuromuscular", "and impaired neuromuscular junction", "impaired neuromuscular junction development.", "neuromuscular junction development. sufferers", "junction development. sufferers of", "development. sufferers of cmsta1", "sufferers of cmsta1 show", "of cmsta1 show a", "cmsta1 show a good", "show a good response", "a good response to", "good response to acetylcholinesterase", "response to acetylcholinesterase inhibitors", "acetylcholinesterase inhibitors senderek", "inhibitors senderek et", "senderek et al. 2011", "et al. 2011 .", "al. 2011 . the", "2011 . the missense", ". the missense mutations", "the missense mutations observed", "missense mutations observed do", "mutations observed do not", "observed do not always", "do not always result", "not always result in", "always result in significant", "result in significant reduction", "in significant reduction in", "significant reduction in enzyme", "reduction in enzyme activity", "enzyme activity but", "activity but biopsies", "but biopsies show reduced", "biopsies show reduced amounts", "show reduced amounts of", "reduced amounts of gfpt1", "amounts of gfpt1 protein", "of gfpt1 protein suggesting", "gfpt1 protein suggesting increased", "protein suggesting increased turnover", "suggesting increased turnover or", "increased turnover or defective", "turnover or defective translation", "defective translation senderek", "translation senderek et", "glucosamine fructose 6 phosphate aminotransferases", "fructose 6 phosphate aminotransferases 1", "6 phosphate aminotransferases 1 and", "phosphate aminotransferases 1 and 2", "1 and 2 gfpt1", "and 2 gfpt1 2", "gfpt1 2 are the", "2 are the first", "are the first and rate", "the first and rate limiting", "first and rate limiting enzymes", "and rate limiting enzymes in", "rate limiting enzymes in the", "limiting enzymes in the hexosamine", "enzymes in the hexosamine synthesis", "in the hexosamine synthesis pathway", "hexosamine synthesis pathway and", "synthesis pathway and thus", "pathway and thus formation", "and thus formation of hexosamines", "thus formation of hexosamines like", "formation of hexosamines like n", "of hexosamines like n acetylglucosamine", "like n acetylglucosamine glcnac", "n acetylglucosamine glcnac .", "acetylglucosamine glcnac . these", "glcnac . these enzymes probably", ". these enzymes probably play", "these enzymes probably play a", "enzymes probably play a role", "probably play a role in", "play a role in limiting", "a role in limiting the", "role in limiting the availability", "in limiting the availability of", "limiting the availability of substrates", "the availability of substrates for", "availability of substrates for the", "of substrates for the n", "for the n and", "the n and o", "n and o linked", "and o linked glycosylation of", "o linked glycosylation of proteins.", "linked glycosylation of proteins. gfpt1", "glycosylation of proteins. gfpt1 and", "of proteins. gfpt1 and 2", "proteins. gfpt1 and 2 are", "gfpt1 and 2 are required", "and 2 are required for", "2 are required for normal", "are required for normal functioning", "required for normal functioning of", "for normal functioning of neuromuscular", "normal functioning of neuromuscular synaptic", "functioning of neuromuscular synaptic transmission.", "of neuromuscular synaptic transmission. defects", "neuromuscular synaptic transmission. defects in", "synaptic transmission. defects in gfpt1", "transmission. defects in gfpt1 lead", "defects in gfpt1 lead to", "in gfpt1 lead to myasthenia", "lead to myasthenia congenital", "myasthenia congenital with", "congenital with tubular aggregates", "tubular aggregates 1 cmsta1", "1 cmsta1 mim:610542", "mim:610542 characterised by", "610542 characterised by", "characterised by altered muscle fibre", "by altered muscle fibre morphology", "altered muscle fibre morphology and", "muscle fibre morphology and impaired", "fibre morphology and impaired neuromuscular", "morphology and impaired neuromuscular junction", "and impaired neuromuscular junction development.", "impaired neuromuscular junction development. sufferers", "neuromuscular junction development. sufferers of", "junction development. sufferers of cmsta1", "development. sufferers of cmsta1 show", "sufferers of cmsta1 show a", "of cmsta1 show a good", "cmsta1 show a good response", "show a good response to", "a good response to acetylcholinesterase", "good response to acetylcholinesterase inhibitors", "to acetylcholinesterase inhibitors senderek", "acetylcholinesterase inhibitors senderek et", "inhibitors senderek et al.", "senderek et al. 2011 .", "et al. 2011 . the", "al. 2011 . the missense", "2011 . the missense mutations", ". the missense mutations observed", "the missense mutations observed do", "missense mutations observed do not", "mutations observed do not always", "observed do not always result", "do not always result in", "not always result in significant", "always result in significant reduction", "result in significant reduction in", "in significant reduction in enzyme", "significant reduction in enzyme activity", "in enzyme activity but", "enzyme activity but biopsies", "activity but biopsies show", "but biopsies show reduced amounts", "biopsies show reduced amounts of", "show reduced amounts of gfpt1", "reduced amounts of gfpt1 protein", "amounts of gfpt1 protein suggesting", "of gfpt1 protein suggesting increased", "gfpt1 protein suggesting increased turnover", "protein suggesting increased turnover or", "suggesting increased turnover or defective", "increased turnover or defective translation", "or defective translation senderek", "defective translation senderek et", "translation senderek et al." ] }, { "record_id": "GLY_000594_1_1652", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "425366", "r hsa", "hsa 425366", "r hsa 425366" ] }, { "record_id": "GLY_000594_1_1652", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transport of", "of bile", "bile salts", "salts and", "and organic", "organic acids", "metal ions", "ions and", "and amine", "amine compounds", "transport of bile", "of bile salts", "bile salts and", "salts and organic", "and organic acids", "acids metal", "metal ions and", "ions and amine", "and amine compounds", "transport of bile salts", "of bile salts and", "bile salts and organic", "salts and organic acids", "organic acids metal", "acids metal ions", "metal ions and amine", "ions and amine compounds", "transport of bile salts and", "of bile salts and organic", "bile salts and organic acids", "and organic acids metal", "organic acids metal ions", "acids metal ions and", "metal ions and amine compounds", "slc transporters", "transporters described", "described in", "in this", "this section", "section transport", "transport bile", "amine compounds.
              myo", "compounds.
              myo inositol", "inositol is", "is a", "a neutral", "neutral cyclic", "cyclic polyol", "abundant in", "in mammalian", "mammalian tissues.", "tissues. it", "it is", "a precursor", "precursor to", "to phosphatidylinositols", "and to", "to the", "the inositol", "inositol phosphates", "which serve", "serve as", "as second", "second messengers", "messengers and", "and also", "also act", "act as", "as key", "key regulators", "regulators of", "of many", "many cell", "cell functions.", "functions. three", "three members", "members of", "of the", "the glucose", "glucose transporter", "transporter gene", "gene family", "family encode", "encode inositol", "inositol transporters", "slc5a3 and", "and slc5a11", "schneider 2015", "2015 .
              five", ".
              five human", "human slc13", "slc13 genes", "genes encode", "encode sodium", "sodium coupled", "coupled sulphate", "and tri", "tri carboxylate", "carboxylate transporters", "transporters typically", "typically located", "located on", "on the", "the plasma", "plasma membrane", "membrane of", "of mammalian", "mammalian cells", "pajor 2006", "2006 .
              the", ".
              the slc16a", "slc16a gene", "encode proton", "proton linked", "linked monocarboxylate", "monocarboxylate transporters", "which mediate", "mediate the", "the transport", "of monocarboxylates", "monocarboxylates such", "such as", "as lactate", "lactate and", "and pyruvate", "major energy", "energy sources", "sources for", "for all", "all cells", "cells in", "in the", "the body", "body so", "so their", "their transport", "transport in", "in and", "and out", "out of", "of cells", "cells is", "is crucial", "crucial for", "for cellular", "cellular function", "morris &", "& felmlee", "felmlee 2008", "2008 .
              the", ".
              the transport", "of essential", "essential metals", "metals and", "and other", "other nutrients", "nutrients across", "across tight", "tight membrane", "membrane barriers", "barriers such", "as the", "the gastrointestinal", "gastrointestinal tract", "tract and", "and blood", "blood brain", "brain barrier", "barrier is", "is mediated", "mediated by", "by metal", "metal transporting", "transporting proteins", "encoded by", "by slc11", "slc40 and", "and slc41", "slc41 .", ". they", "they can", "can also", "also regulate", "regulate metals", "metals by", "by efflux", "efflux out", "cells and", "and cellular", "cellular compartments", "compartments to", "to avoid", "avoid toxic", "toxic build", "build up", "bressler et", "et al.", "al. 2007", "2007 .
              the", ".
              the slc6", "slc6 gene", "family encodes", "encodes proteins", "proteins that", "that mediate", "mediate neurotransmitter", "neurotransmitter uptake", "uptake in", "the central", "central nervous", "nervous system", "and peripheral", "peripheral nervous", "thus terminating", "terminating a", "a synaptic", "synaptic signal.", "signal. the", "the proteins", "proteins mediate", "mediate transport", "of gaba", "gamma aminobutyric", "aminobutyric acid", "l proline", "creatine and", "and betaine", "chen et", "al. 2004", "2004 .
              carrier", ".
              carrier mediated", "mediated urea", "urea transport", "transport allows", "allows rapid", "rapid urea", "urea movement", "movement across", "across the", "the cell", "cell membrane", "which is", "is particularly", "particularly important", "important in", "the process", "process of", "of urinary", "urinary concentration", "concentration and", "and for", "for rapid", "urea equilibrium", "equilibrium in", "in non", "non renal", "renal tissues.", "tissues. two", "two carriers", "carriers exist", "exist in", "in humans", "by slc14a1", "slc14a1 and", "and alc14a2", "olives et", "al. 1994", "1994 .
              choline", ".
              choline uptake", "uptake is", "is the", "the rate", "rate limiting", "limiting step", "step in", "the synthesis", "synthesis of", "the neurotransmitter", "neurotransmitter acetylcholine.", "acetylcholine. slc", "slc genes", "genes slc5a7", "slc5a7 and", "and the", "the slc44", "slc44 family", "encode choline", "choline transporters", "okuda &", "& haga", "haga 2000", "traiffort et", "al. 2005", "2005 .
              the", ".
              the slc22", "slc22 gene", "family of", "of solute", "solute carriers", "carriers function", "function as", "as organic", "organic cation", "cation transporters", "cation/zwitterion transporters", "organic anion", "anion transporters", "oats .", ". most", "most of", "of this", "this family", "family are", "are polyspecific", "polyspecific transporters.", "transporters. since", "since many", "many of", "of these", "these transporters", "transporters are", "are expressed", "expressed in", "the liver", "kidney and", "and intestine", "they play", "play an", "an important", "important role", "role in", "in drug", "drug absorption", "absorption and", "and excretion.", "excretion. substrates", "substrates include", "include xenobiotics", "and endogenous", "endogenous amine", "koepsell &", "& endou", "endou 2004", "2004 .", "slc transporters described", "transporters described in", "described in this", "in this section", "this section transport", "section transport bile", "transport bile salts", "salts organic", "and amine compounds.
              myo", "amine compounds.
              myo inositol", "compounds.
              myo inositol is", "inositol is a", "is a neutral", "a neutral cyclic", "neutral cyclic polyol", "polyol abundant", "abundant in mammalian", "in mammalian tissues.", "mammalian tissues. it", "tissues. it is", "it is a", "is a precursor", "a precursor to", "precursor to phosphatidylinositols", "phosphatidylinositols ptdins", "ptdins and", "and to the", "to the inositol", "the inositol phosphates", "phosphates ip", "which serve as", "serve as second", "as second messengers", "second messengers and", "messengers and also", "and also act", "also act as", "act as key", "as key regulators", "key regulators of", "regulators of many", "of many cell", "many cell functions.", "cell functions. three", "functions. three members", "three members of", "members of the", "of the glucose", "the glucose transporter", "glucose transporter gene", "transporter gene family", "gene family encode", "family encode inositol", "encode inositol transporters", "transporters slc2a13", "slc2a13 slc5a3", "slc5a3 and slc5a11", "schneider 2015 .
              five", "2015 .
              five human", ".
              five human slc13", "human slc13 genes", "slc13 genes encode", "genes encode sodium", "encode sodium coupled", "sodium coupled sulphate", "sulphate di", "di and", "and tri carboxylate", "tri carboxylate transporters", "carboxylate transporters typically", "transporters typically located", "typically located on", "located on the", "on the plasma", "the plasma membrane", "plasma membrane of", "membrane of mammalian", "of mammalian cells", "cells pajor", "pajor 2006 .
              the", "2006 .
              the slc16a", ".
              the slc16a gene", "slc16a gene family", "family encode proton", "encode proton linked", "proton linked monocarboxylate", "linked monocarboxylate transporters", "transporters mct", "mct which", "which mediate the", "mediate the transport", "the transport of", "transport of monocarboxylates", "of monocarboxylates such", "monocarboxylates such as", "such as lactate", "as lactate and", "lactate and pyruvate", "pyruvate major", "major energy sources", "energy sources for", "sources for all", "for all cells", "all cells in", "cells in the", "in the body", "the body so", "body so their", "so their transport", "their transport in", "transport in and", "in and out", "and out of", "out of cells", "of cells is", "cells is crucial", "is crucial for", "crucial for cellular", "for cellular function", "function morris", "morris & felmlee", "& felmlee 2008", "felmlee 2008 .
              the", "2008 .
              the transport", ".
              the transport of", "transport of essential", "of essential metals", "essential metals and", "metals and other", "and other nutrients", "other nutrients across", "nutrients across tight", "across tight membrane", "tight membrane barriers", "membrane barriers such", "barriers such as", "such as the", "as the gastrointestinal", "the gastrointestinal tract", "gastrointestinal tract and", "tract and blood", "and blood brain", "blood brain barrier", "brain barrier is", "barrier is mediated", "is mediated by", "mediated by metal", "by metal transporting", "metal transporting proteins", "proteins encoded", "encoded by slc11", "slc11 slc30", "slc30 slc31", "slc31 slc39", "slc39 slc40", "slc40 and slc41", "and slc41 .", "slc41 . they", ". they can", "they can also", "can also regulate", "also regulate metals", "regulate metals by", "metals by efflux", "by efflux out", "efflux out of", "of cells and", "cells and cellular", "and cellular compartments", "cellular compartments to", "compartments to avoid", "to avoid toxic", "avoid toxic build", "toxic build up", "up bressler", "bressler et al.", "et al. 2007", "al. 2007 .
              the", "2007 .
              the slc6", ".
              the slc6 gene", "slc6 gene family", "gene family encodes", "family encodes proteins", "encodes proteins that", "proteins that mediate", "that mediate neurotransmitter", "mediate neurotransmitter uptake", "neurotransmitter uptake in", "uptake in the", "in the central", "the central nervous", "central nervous system", "system csn", "csn and", "and peripheral nervous", "peripheral nervous system", "system pns", "thus terminating a", "terminating a synaptic", "a synaptic signal.", "synaptic signal. the", "signal. the proteins", "the proteins mediate", "proteins mediate transport", "mediate transport of", "transport of gaba", "gaba gamma", "gamma aminobutyric acid", "norepinephrine dopamine", "dopamine serotonin", "serotonin glycine", "glycine taurine", "taurine l", "proline creatine", "creatine and betaine", "betaine chen", "chen et al.", "et al. 2004", "al. 2004 .
              carrier", "2004 .
              carrier mediated", ".
              carrier mediated urea", "mediated urea transport", "urea transport allows", "transport allows rapid", "allows rapid urea", "rapid urea movement", "urea movement across", "movement across the", "across the cell", "the cell membrane", "membrane which", "which is particularly", "is particularly important", "particularly important in", "important in the", "in the process", "the process of", "process of urinary", "of urinary concentration", "urinary concentration and", "concentration and for", "and for rapid", "for rapid urea", "rapid urea equilibrium", "urea equilibrium in", "equilibrium in non", "in non renal", "non renal tissues.", "renal tissues. two", "tissues. two carriers", "two carriers exist", "carriers exist in", "exist in humans", "humans encoded", "encoded by slc14a1", "by slc14a1 and", "slc14a1 and alc14a2", "alc14a2 olives", "olives et al.", "et al. 1994", "al. 1994 .
              choline", "1994 .
              choline uptake", ".
              choline uptake is", "uptake is the", "is the rate", "the rate limiting", "rate limiting step", "limiting step in", "step in the", "in the synthesis", "the synthesis of", "synthesis of the", "of the neurotransmitter", "the neurotransmitter acetylcholine.", "neurotransmitter acetylcholine. slc", "acetylcholine. slc genes", "slc genes slc5a7", "genes slc5a7 and", "slc5a7 and the", "and the slc44", "the slc44 family", "slc44 family encode", "family encode choline", "encode choline transporters", "okuda & haga", "& haga 2000", "2000 traiffort", "traiffort et al.", "et al. 2005", "al. 2005 .
              the", "2005 .
              the slc22", ".
              the slc22 gene", "slc22 gene family", "gene family of", "family of solute", "of solute carriers", "solute carriers function", "carriers function as", "function as organic", "as organic cation", "organic cation transporters", "transporters octs", "transporters octns", "octns and", "and organic anion", "organic anion transporters", "transporters oats", "oats . most", ". most of", "most of this", "of this family", "this family are", "family are polyspecific", "are polyspecific transporters.", "polyspecific transporters. since", "transporters. since many", "since many of", "many of these", "of these transporters", "these transporters are", "transporters are expressed", "are expressed in", "expressed in the", "in the liver", "liver kidney", "kidney and intestine", "intestine they", "they play an", "play an important", "an important role", "important role in", "role in drug", "in drug absorption", "drug absorption and", "absorption and excretion.", "and excretion. substrates", "excretion. substrates include", "substrates include xenobiotics", "xenobiotics drugs", "drugs and", "and endogenous amine", "endogenous amine compounds", "compounds koepsell", "koepsell & endou", "& endou 2004", "endou 2004 .", "slc transporters described in", "transporters described in this", "described in this section", "in this section transport", "this section transport bile", "section transport bile salts", "bile salts organic", "salts organic acids", "ions and amine compounds.
              myo", "and amine compounds.
              myo inositol", "amine compounds.
              myo inositol is", "compounds.
              myo inositol is a", "inositol is a neutral", "is a neutral cyclic", "a neutral cyclic polyol", "cyclic polyol abundant", "polyol abundant in", "abundant in mammalian tissues.", "in mammalian tissues. it", "mammalian tissues. it is", "tissues. it is a", "it is a precursor", "is a precursor to", "a precursor to phosphatidylinositols", "to phosphatidylinositols ptdins", "ptdins and to", "and to the inositol", "to the inositol phosphates", "inositol phosphates ip", "ip which", "which serve as second", "serve as second messengers", "as second messengers and", "second messengers and also", "messengers and also act", "and also act as", "also act as key", "act as key regulators", "as key regulators of", "key regulators of many", "regulators of many cell", "of many cell functions.", "many cell functions. three", "cell functions. three members", "functions. three members of", "three members of the", "members of the glucose", "of the glucose transporter", "the glucose transporter gene", "glucose transporter gene family", "transporter gene family encode", "gene family encode inositol", "family encode inositol transporters", "inositol transporters slc2a13", "slc2a13 slc5a3 and", "slc5a11 schneider", "schneider 2015 .
              five human", "2015 .
              five human slc13", ".
              five human slc13 genes", "human slc13 genes encode", "slc13 genes encode sodium", "genes encode sodium coupled", "encode sodium coupled sulphate", "coupled sulphate di", "di and tri", "and tri carboxylate transporters", "tri carboxylate transporters typically", "carboxylate transporters typically located", "transporters typically located on", "typically located on the", "located on the plasma", "on the plasma membrane", "the plasma membrane of", "plasma membrane of mammalian", "membrane of mammalian cells", "mammalian cells pajor", "cells pajor 2006", "pajor 2006 .
              the slc16a", "2006 .
              the slc16a gene", ".
              the slc16a gene family", "slc16a gene family encode", "gene family encode proton", "family encode proton linked", "encode proton linked monocarboxylate", "proton linked monocarboxylate transporters", "monocarboxylate transporters mct", "mct which mediate", "which mediate the transport", "mediate the transport of", "the transport of monocarboxylates", "transport of monocarboxylates such", "of monocarboxylates such as", "monocarboxylates such as lactate", "such as lactate and", "as lactate and pyruvate", "and pyruvate major", "pyruvate major energy", "major energy sources for", "energy sources for all", "sources for all cells", "for all cells in", "all cells in the", "cells in the body", "in the body so", "the body so their", "body so their transport", "so their transport in", "their transport in and", "transport in and out", "in and out of", "and out of cells", "out of cells is", "of cells is crucial", "cells is crucial for", "is crucial for cellular", "crucial for cellular function", "cellular function morris", "function morris &", "morris & felmlee 2008", "& felmlee 2008 .
              the", "felmlee 2008 .
              the transport", "2008 .
              the transport of", ".
              the transport of essential", "transport of essential metals", "of essential metals and", "essential metals and other", "metals and other nutrients", "and other nutrients across", "other nutrients across tight", "nutrients across tight membrane", "across tight membrane barriers", "tight membrane barriers such", "membrane barriers such as", "barriers such as the", "such as the gastrointestinal", "as the gastrointestinal tract", "the gastrointestinal tract and", "gastrointestinal tract and blood", "tract and blood brain", "and blood brain barrier", "blood brain barrier is", "brain barrier is mediated", "barrier is mediated by", "is mediated by metal", "mediated by metal transporting", "by metal transporting proteins", "transporting proteins encoded", "proteins encoded by", "by slc11 slc30", "slc39 slc40 and", "slc40 and slc41 .", "and slc41 . they", "slc41 . they can", ". they can also", "they can also regulate", "can also regulate metals", "also regulate metals by", "regulate metals by efflux", "metals by efflux out", "by efflux out of", "efflux out of cells", "out of cells and", "of cells and cellular", "cells and cellular compartments", "and cellular compartments to", "cellular compartments to avoid", "compartments to avoid toxic", "to avoid toxic build", "avoid toxic build up", "build up bressler", "up bressler et", "bressler et al. 2007", "et al. 2007 .
              the", "al. 2007 .
              the slc6", "2007 .
              the slc6 gene", ".
              the slc6 gene family", "slc6 gene family encodes", "gene family encodes proteins", "family encodes proteins that", "encodes proteins that mediate", "proteins that mediate neurotransmitter", "that mediate neurotransmitter uptake", "mediate neurotransmitter uptake in", "neurotransmitter uptake in the", "uptake in the central", "in the central nervous", "the central nervous system", "nervous system csn", "csn and peripheral", "and peripheral nervous system", "nervous system pns", "pns thus", "thus terminating a synaptic", "terminating a synaptic signal.", "a synaptic signal. the", "synaptic signal. the proteins", "signal. the proteins mediate", "the proteins mediate transport", "proteins mediate transport of", "mediate transport of gaba", "of gaba gamma", "gaba gamma aminobutyric", "acid norepinephrine", "taurine l proline", "l proline creatine", "proline creatine and", "and betaine chen", "betaine chen et", "chen et al. 2004", "et al. 2004 .
              carrier", "al. 2004 .
              carrier mediated", "2004 .
              carrier mediated urea", ".
              carrier mediated urea transport", "mediated urea transport allows", "urea transport allows rapid", "transport allows rapid urea", "allows rapid urea movement", "rapid urea movement across", "urea movement across the", "movement across the cell", "across the cell membrane", "cell membrane which", "membrane which is", "which is particularly important", "is particularly important in", "particularly important in the", "important in the process", "in the process of", "the process of urinary", "process of urinary concentration", "of urinary concentration and", "urinary concentration and for", "concentration and for rapid", "and for rapid urea", "for rapid urea equilibrium", "rapid urea equilibrium in", "urea equilibrium in non", "equilibrium in non renal", "in non renal tissues.", "non renal tissues. two", "renal tissues. two carriers", "tissues. two carriers exist", "two carriers exist in", "carriers exist in humans", "in humans encoded", "humans encoded by", "encoded by slc14a1 and", "by slc14a1 and alc14a2", "and alc14a2 olives", "alc14a2 olives et", "olives et al. 1994", "et al. 1994 .
              choline", "al. 1994 .
              choline uptake", "1994 .
              choline uptake is", ".
              choline uptake is the", "uptake is the rate", "is the rate limiting", "the rate limiting step", "rate limiting step in", "limiting step in the", "step in the synthesis", "in the synthesis of", "the synthesis of the", "synthesis of the neurotransmitter", "of the neurotransmitter acetylcholine.", "the neurotransmitter acetylcholine. slc", "neurotransmitter acetylcholine. slc genes", "acetylcholine. slc genes slc5a7", "slc genes slc5a7 and", "genes slc5a7 and the", "slc5a7 and the slc44", "and the slc44 family", "the slc44 family encode", "slc44 family encode choline", "family encode choline transporters", "transporters okuda", "okuda & haga 2000", "haga 2000 traiffort", "2000 traiffort et", "traiffort et al. 2005", "et al. 2005 .
              the", "al. 2005 .
              the slc22", "2005 .
              the slc22 gene", ".
              the slc22 gene family", "slc22 gene family of", "gene family of solute", "family of solute carriers", "of solute carriers function", "solute carriers function as", "carriers function as organic", "function as organic cation", "as organic cation transporters", "cation transporters octs", "octs cation/zwitterion", "cation/zwitterion transporters octns", "octns and organic", "and organic anion transporters", "anion transporters oats", "transporters oats .", "oats . most of", ". most of this", "most of this family", "of this family are", "this family are polyspecific", "family are polyspecific transporters.", "are polyspecific transporters. since", "polyspecific transporters. since many", "transporters. since many of", "since many of these", "many of these transporters", "of these transporters are", "these transporters are expressed", "transporters are expressed in", "are expressed in the", "expressed in the liver", "the liver kidney", "liver kidney and", "and intestine they", "intestine they play", "they play an important", "play an important role", "an important role in", "important role in drug", "role in drug absorption", "in drug absorption and", "drug absorption and excretion.", "absorption and excretion. substrates", "and excretion. substrates include", "excretion. substrates include xenobiotics", "include xenobiotics drugs", "drugs and endogenous", "and endogenous amine compounds", "amine compounds koepsell", "compounds koepsell &", "koepsell & endou 2004", "& endou 2004 .", "slc transporters described in this", "transporters described in this section", "described in this section transport", "in this section transport bile", "this section transport bile salts", "transport bile salts organic", "bile salts organic acids", "metal ions and amine compounds.
              myo", "ions and amine compounds.
              myo inositol", "and amine compounds.
              myo inositol is", "amine compounds.
              myo inositol is a", "compounds.
              myo inositol is a neutral", "inositol is a neutral cyclic", "is a neutral cyclic polyol", "neutral cyclic polyol abundant", "cyclic polyol abundant in", "polyol abundant in mammalian", "abundant in mammalian tissues. it", "in mammalian tissues. it is", "mammalian tissues. it is a", "tissues. it is a precursor", "it is a precursor to", "is a precursor to phosphatidylinositols", "precursor to phosphatidylinositols ptdins", "phosphatidylinositols ptdins and", "ptdins and to the", "and to the inositol phosphates", "the inositol phosphates ip", "ip which serve", "which serve as second messengers", "serve as second messengers and", "as second messengers and also", "second messengers and also act", "messengers and also act as", "and also act as key", "also act as key regulators", "act as key regulators of", "as key regulators of many", "key regulators of many cell", "regulators of many cell functions.", "of many cell functions. three", "many cell functions. three members", "cell functions. three members of", "functions. three members of the", "three members of the glucose", "members of the glucose transporter", "of the glucose transporter gene", "the glucose transporter gene family", "glucose transporter gene family encode", "transporter gene family encode inositol", "gene family encode inositol transporters", "encode inositol transporters slc2a13", "transporters slc2a13 slc5a3", "slc2a13 slc5a3 and slc5a11", "and slc5a11 schneider", "slc5a11 schneider 2015", "schneider 2015 .
              five human slc13", "2015 .
              five human slc13 genes", ".
              five human slc13 genes encode", "human slc13 genes encode sodium", "slc13 genes encode sodium coupled", "genes encode sodium coupled sulphate", "sodium coupled sulphate di", "sulphate di and", "di and tri carboxylate", "and tri carboxylate transporters typically", "tri carboxylate transporters typically located", "carboxylate transporters typically located on", "transporters typically located on the", "typically located on the plasma", "located on the plasma membrane", "on the plasma membrane of", "the plasma membrane of mammalian", "plasma membrane of mammalian cells", "of mammalian cells pajor", "mammalian cells pajor 2006", "cells pajor 2006 .
              the", "pajor 2006 .
              the slc16a gene", "2006 .
              the slc16a gene family", ".
              the slc16a gene family encode", "slc16a gene family encode proton", "gene family encode proton linked", "family encode proton linked monocarboxylate", "encode proton linked monocarboxylate transporters", "linked monocarboxylate transporters mct", "transporters mct which", "mct which mediate the", "which mediate the transport of", "mediate the transport of monocarboxylates", "the transport of monocarboxylates such", "transport of monocarboxylates such as", "of monocarboxylates such as lactate", "monocarboxylates such as lactate and", "such as lactate and pyruvate", "lactate and pyruvate major", "and pyruvate major energy", "pyruvate major energy sources", "major energy sources for all", "energy sources for all cells", "sources for all cells in", "for all cells in the", "all cells in the body", "cells in the body so", "in the body so their", "the body so their transport", "body so their transport in", "so their transport in and", "their transport in and out", "transport in and out of", "in and out of cells", "and out of cells is", "out of cells is crucial", "of cells is crucial for", "cells is crucial for cellular", "is crucial for cellular function", "for cellular function morris", "cellular function morris &", "function morris & felmlee", "morris & felmlee 2008 .
              the", "& felmlee 2008 .
              the transport", "felmlee 2008 .
              the transport of", "2008 .
              the transport of essential", ".
              the transport of essential metals", "transport of essential metals and", "of essential metals and other", "essential metals and other nutrients", "metals and other nutrients across", "and other nutrients across tight", "other nutrients across tight membrane", "nutrients across tight membrane barriers", "across tight membrane barriers such", "tight membrane barriers such as", "membrane barriers such as the", "barriers such as the gastrointestinal", "such as the gastrointestinal tract", "as the gastrointestinal tract and", "the gastrointestinal tract and blood", "gastrointestinal tract and blood brain", "tract and blood brain barrier", "and blood brain barrier is", "blood brain barrier is mediated", "brain barrier is mediated by", "barrier is mediated by metal", "is mediated by metal transporting", "mediated by metal transporting proteins", "metal transporting proteins encoded", "transporting proteins encoded by", "proteins encoded by slc11", "encoded by slc11 slc30", "slc11 slc30 slc31", "slc30 slc31 slc39", "slc31 slc39 slc40", "slc39 slc40 and slc41", "slc40 and slc41 . they", "and slc41 . they can", "slc41 . they can also", ". they can also regulate", "they can also regulate metals", "can also regulate metals by", "also regulate metals by efflux", "regulate metals by efflux out", "metals by efflux out of", "by efflux out of cells", "efflux out of cells and", "out of cells and cellular", "of cells and cellular compartments", "cells and cellular compartments to", "and cellular compartments to avoid", "cellular compartments to avoid toxic", "compartments to avoid toxic build", "to avoid toxic build up", "toxic build up bressler", "build up bressler et", "up bressler et al.", "bressler et al. 2007 .
              the", "et al. 2007 .
              the slc6", "al. 2007 .
              the slc6 gene", "2007 .
              the slc6 gene family", ".
              the slc6 gene family encodes", "slc6 gene family encodes proteins", "gene family encodes proteins that", "family encodes proteins that mediate", "encodes proteins that mediate neurotransmitter", "proteins that mediate neurotransmitter uptake", "that mediate neurotransmitter uptake in", "mediate neurotransmitter uptake in the", "neurotransmitter uptake in the central", "uptake in the central nervous", "in the central nervous system", "central nervous system csn", "system csn and", "csn and peripheral nervous", "peripheral nervous system pns", "pns thus terminating", "thus terminating a synaptic signal.", "terminating a synaptic signal. the", "a synaptic signal. the proteins", "synaptic signal. the proteins mediate", "signal. the proteins mediate transport", "the proteins mediate transport of", "proteins mediate transport of gaba", "transport of gaba gamma", "of gaba gamma aminobutyric", "gaba gamma aminobutyric acid", "aminobutyric acid norepinephrine", "norepinephrine dopamine serotonin", "dopamine serotonin glycine", "serotonin glycine taurine", "glycine taurine l", "l proline creatine and", "proline creatine and betaine", "creatine and betaine chen", "and betaine chen et", "betaine chen et al.", "chen et al. 2004 .
              carrier", "et al. 2004 .
              carrier mediated", "al. 2004 .
              carrier mediated urea", "2004 .
              carrier mediated urea transport", ".
              carrier mediated urea transport allows", "mediated urea transport allows rapid", "urea transport allows rapid urea", "transport allows rapid urea movement", "allows rapid urea movement across", "rapid urea movement across the", "urea movement across the cell", "movement across the cell membrane", "the cell membrane which", "cell membrane which is", "membrane which is particularly", "which is particularly important in", "is particularly important in the", "particularly important in the process", "important in the process of", "in the process of urinary", "the process of urinary concentration", "process of urinary concentration and", "of urinary concentration and for", "urinary concentration and for rapid", "concentration and for rapid urea", "and for rapid urea equilibrium", "for rapid urea equilibrium in", "rapid urea equilibrium in non", "urea equilibrium in non renal", "equilibrium in non renal tissues.", "in non renal tissues. two", "non renal tissues. two carriers", "renal tissues. two carriers exist", "tissues. two carriers exist in", "two carriers exist in humans", "exist in humans encoded", "in humans encoded by", "humans encoded by slc14a1", "encoded by slc14a1 and alc14a2", "slc14a1 and alc14a2 olives", "and alc14a2 olives et", "alc14a2 olives et al.", "olives et al. 1994 .
              choline", "et al. 1994 .
              choline uptake", "al. 1994 .
              choline uptake is", "1994 .
              choline uptake is the", ".
              choline uptake is the rate", "uptake is the rate limiting", "is the rate limiting step", "the rate limiting step in", "rate limiting step in the", "limiting step in the synthesis", "step in the synthesis of", "in the synthesis of the", "the synthesis of the neurotransmitter", "synthesis of the neurotransmitter acetylcholine.", "of the neurotransmitter acetylcholine. slc", "the neurotransmitter acetylcholine. slc genes", "neurotransmitter acetylcholine. slc genes slc5a7", "acetylcholine. slc genes slc5a7 and", "slc genes slc5a7 and the", "genes slc5a7 and the slc44", "slc5a7 and the slc44 family", "and the slc44 family encode", "the slc44 family encode choline", "slc44 family encode choline transporters", "choline transporters okuda", "transporters okuda &", "& haga 2000 traiffort", "haga 2000 traiffort et", "2000 traiffort et al.", "traiffort et al. 2005 .
              the", "et al. 2005 .
              the slc22", "al. 2005 .
              the slc22 gene", "2005 .
              the slc22 gene family", ".
              the slc22 gene family of", "slc22 gene family of solute", "gene family of solute carriers", "family of solute carriers function", "of solute carriers function as", "solute carriers function as organic", "carriers function as organic cation", "function as organic cation transporters", "organic cation transporters octs", "octs cation/zwitterion transporters", "transporters octns and", "octns and organic anion", "organic anion transporters oats", "anion transporters oats .", "transporters oats . most", "oats . most of this", ". most of this family", "most of this family are", "of this family are polyspecific", "this family are polyspecific transporters.", "family are polyspecific transporters. since", "are polyspecific transporters. since many", "polyspecific transporters. since many of", "transporters. since many of these", "since many of these transporters", "many of these transporters are", "of these transporters are expressed", "these transporters are expressed in", "transporters are expressed in the", "are expressed in the liver", "in the liver kidney", "the liver kidney and", "liver kidney and intestine", "kidney and intestine they", "and intestine they play", "intestine they play an", "they play an important role", "play an important role in", "an important role in drug", "important role in drug absorption", "role in drug absorption and", "in drug absorption and excretion.", "drug absorption and excretion. substrates", "absorption and excretion. substrates include", "and excretion. substrates include xenobiotics", "substrates include xenobiotics drugs", "xenobiotics drugs and", "drugs and endogenous amine", "endogenous amine compounds koepsell", "amine compounds koepsell &", "compounds koepsell & endou", "koepsell & endou 2004 ." ] }, { "record_id": "GLY_000594_1_1653", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "426048", "r hsa", "hsa 426048", "r hsa 426048" ] }, { "record_id": 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426117", "r hsa 426117" ] }, { "record_id": "GLY_000594_1_1654", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cation coupled", "coupled chloride", "chloride cotransporters", "cation coupled chloride", "coupled chloride cotransporters", "cation coupled chloride cotransporters", "the cation", "cation chloride", "chloride cotransporter", "cotransporter family", "slc12 gene", "gene family", "are membrane", "membrane proteins", "proteins that", "that cotranslocate", "cotranslocate chloride", "with either", "either na+", "or both", "both cations", "cations electroneutrally.", "electroneutrally. the", "the general", "general topology", "topology of", "of these", "these proteins", "proteins feature", "feature 12", "12 transmembrane", "transmembrane domains", "domains flanked", "flanked by", "by hydrophilic", "hydrophilic nh2", "nh2 and", "and cooh", "cooh terminal", "terminal domains.", "domains. they", "they are", "are secondary", "secondary 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              two", ".

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              two members", ".

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              two", "2004 .

              two members of", ".

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              two", "rh 2004 .

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"phosphatidylinositols ptdins and", "ptdins and to the", "and to the inositol phosphates", "the inositol phosphates ip", "ip which serve", "which serve as second messengers", "serve as second messengers and", "as second messengers and as", "second messengers and as key", "messengers and as key regulators", "and as key regulators of", "as key regulators of many", "key regulators of many cell", "regulators of many cell functions.", "of many cell functions. it", "many cell functions. it can", "cell functions. it can also", "functions. it can also serve", "it can also serve as", "can also serve as a", "also serve as a compatible", "serve as a compatible osmolyte", "as a compatible osmolyte during", "a compatible osmolyte during volume", "compatible osmolyte during volume regulation", "osmolyte during volume regulation in", "during volume regulation in many", "volume regulation in many tissues", "regulation in many tissues where", "in many tissues where cells", "many tissues where cells are", "tissues where cells are exposed", "where cells are exposed to", "cells are exposed to hyperosmotic", "are exposed to hyperosmotic conditions.", "exposed to hyperosmotic conditions. three", "to hyperosmotic conditions. three members", "hyperosmotic conditions. three members of", "conditions. three members of the", "three members of the glucose", "members of the glucose transporter", "of the glucose transporter families", "the glucose transporter families are", "glucose transporter families are inositol", "transporter families are inositol transporters.", "families are inositol transporters. two", "inositol transporters. two smit1", "transporters. two smit1 and", "two smit1 and smit2", "smit1 and smit2 couple", "and smit2 couple myo", "smit2 couple myo inositol", "couple myo inositol transport with", "myo inositol transport with two", "inositol transport with two na+", "transport with two na+ ions.", "with two na+ ions. unlike", "two na+ ions. unlike smit1", "ions. unlike smit1 smit2", "unlike smit1 smit2 also", "smit1 smit2 also transports", "smit2 also transports d chiro_inositol.", "also transports d chiro_inositol. the", "transports d chiro_inositol. the third", "d chiro_inositol. the third transporter", "the third transporter hmit", "hmit couples myo", "couples myo inositol transport with", "myo inositol transport with a", "inositol transport with a proton." ] }, { "record_id": "GLY_000594_1_1661", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "429958", "r hsa", "hsa 429958", "r hsa 429958" ] }, { "record_id": "GLY_000594_1_1661", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna decay", "decay by", "by 3'", "3' to", "to 5'", "5' exoribonuclease", "mrna decay by", "decay by 3'", "by 3' to", "3' to 5'", "to 5' exoribonuclease", "mrna decay by 3'", "decay by 3' to", "by 3' to 5'", "3' to 5' exoribonuclease", "mrna decay by 3' to", "decay by 3' to 5'", "by 3' to 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ion transporters. all", "ion transporters. all zips", "transporters. all zips transport", "all zips transport metal", "zips transport metal ions", "transport metal ions into", "metal ions into the", "ions into the cytoplasm", "into the cytoplasm of", "the cytoplasm of cells", "of cells be", "cells be it", "be it across cellular", "it across cellular membranes", "across cellular membranes or", "cellular membranes or from", "membranes or from intracellular", "or from intracellular compartments.", "from intracellular compartments. to", "intracellular compartments. to date", "to date there", "date there are", "there are 14 human", "are 14 human slc39", "14 human slc39 genes", "human slc39 genes that", "slc39 genes that encode", "genes that encode the", "that encode the zinc", "encode the zinc transporters", "the zinc transporters hzip1", "zinc transporters hzip1 14.", "transporters hzip1 14. there", "hzip1 14. there are", "14. there are 9", "there are 9 members", "are 9 members which", "9 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slc39 genes that encode", "slc39 genes that encode the", "genes that encode the zinc", "that encode the zinc transporters", "encode the zinc transporters hzip1", "the zinc transporters hzip1 14.", "zinc transporters hzip1 14. there", "transporters hzip1 14. there are", "hzip1 14. there are 9", "14. there are 9 members", "there are 9 members which", "are 9 members which belong", "9 members which belong to", "members which belong to a", "which belong to a subfamily", "belong to a subfamily of", "to a subfamily of the", "a subfamily of the zips", "subfamily of the zips called", "of the zips called the", "the zips called the lzts", "called the lzts liv", "the lzts liv 1", "lzts liv 1 subfamily", "liv 1 subfamily of zip", "1 subfamily of zip zinc", "subfamily of zip zinc transporters", "zinc transporters taylor", "transporters taylor km", "taylor km and nicholson ri", "and nicholson ri 2003", "nicholson ri 2003 .", "ri 2003 . of", "2003 . of these 14", ". of these 14 proteins", "these 14 proteins four", "proteins four hzip9", "four hzip9 11", "hzip9 11 12", "11 12 and 13", "12 and 13 have", "and 13 have no", "13 have no function", "have no function determined yet", "function determined yet eide", "determined yet eide dj", "eide dj 2004 ." ] }, { "record_id": "GLY_000594_1_1665", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "444411", "r hsa", "hsa 444411", "r hsa 444411" ] }, { "record_id": "GLY_000594_1_1665", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhesus glycoproteins", "glycoproteins mediate", "mediate ammonium", "ammonium transport", "rhesus glycoproteins mediate", "glycoproteins mediate ammonium", "mediate ammonium transport", "rhesus glycoproteins mediate ammonium", "glycoproteins mediate ammonium transport", "rhesus glycoproteins mediate ammonium transport", "the rhesus", "glycoproteins were", "were originally", "originally described", "described in", "in human", "human blood", "blood cells", "cells as", "as potent", "potent immunogens.", "immunogens. there", "there are", "are three", "three rh", "rh glycoproteins", "glycoproteins in", "in humans", "an erythroid", "erythroid specific", "specific rh", "rh associated", "associated glycoprotein", "and two", "two non", "non erythroid", "erythroid rh", "rhbg and", "and rhcg.", "rhcg. these", "these proteins", "proteins are", "are related", "related to", "to ammonium", "transporters of", "of yeast", "yeast and", "and bacteria", "methylammonium and", "and ammonium", "ammonium permease", "permease and", "ammonium transporter", "nakhoul nl", "nl and", "and hamm", "hamm ll", "planelles g", "2007 .", "rhesus rh", "glycoproteins were originally", "were originally described", "originally described in", "described in human", "in human blood", "human blood cells", "blood cells as", "cells as potent", "as potent immunogens.", "potent immunogens. there", "immunogens. there are", "there are three", "are three rh", "three rh glycoproteins", "rh glycoproteins in", "glycoproteins in humans", "humans an", "an erythroid specific", "erythroid specific rh", "specific rh associated", "rh associated glycoprotein", "glycoprotein rhag", "rhag and", "and two non", "two non erythroid", "non erythroid rh", "erythroid rh glycoproteins", "glycoproteins rhbg", "rhbg and rhcg.", "and rhcg. these", "rhcg. these proteins", "these proteins are", "proteins are related", "are related to", "related to ammonium", "ammonium nh4+", "nh4+ transporters", "transporters of yeast", "of yeast and", "yeast and bacteria", "bacteria methylammonium", "methylammonium and ammonium", "and ammonium permease", "ammonium permease and", "permease and ammonium", "and ammonium transporter", "transporter mep/amt", "nakhoul nl and", "nl and hamm", "and hamm ll", "ll 2004", "2004 planelles", "g 2007", "the rhesus rh", "rh glycoproteins were", "glycoproteins were originally described", "were originally described in", "originally described in human", "described in human blood", "in human blood cells", "human blood cells as", "blood cells as potent", "cells as potent immunogens.", "as potent immunogens. there", "potent immunogens. there are", "immunogens. there are three", "there are three rh", "are three rh glycoproteins", "three rh glycoproteins in", "rh glycoproteins in humans", "in humans an", "humans an erythroid", "an erythroid specific rh", "erythroid specific rh associated", "specific rh associated glycoprotein", "associated glycoprotein rhag", "rhag and two", "and two non erythroid", "two non erythroid rh", "non erythroid rh glycoproteins", "rh glycoproteins rhbg", "glycoproteins rhbg and", "rhbg and rhcg. these", "and rhcg. these proteins", "rhcg. these proteins are", "these proteins are related", "proteins are related to", "are related to ammonium", "to ammonium nh4+", "nh4+ transporters of", "transporters of yeast and", "of yeast and bacteria", "and bacteria methylammonium", "bacteria methylammonium and", "methylammonium and ammonium permease", "and ammonium permease and", "ammonium permease and ammonium", "permease and ammonium transporter", "ammonium transporter mep/amt", "mep/amt nakhoul", "nakhoul nl and hamm", "nl and hamm ll", "hamm ll 2004", "2004 planelles g", "planelles g 2007", "g 2007 .", "rhesus rh glycoproteins", "rh glycoproteins were originally", "glycoproteins were originally described in", "were originally described in human", "originally described in human blood", "described in human blood cells", "in human blood cells as", "human blood cells as potent", "blood cells as potent immunogens.", "cells as potent immunogens. there", "as potent immunogens. there are", "potent immunogens. there are three", "immunogens. there are three rh", "there are three rh glycoproteins", "are three rh glycoproteins in", "three rh glycoproteins in humans", "glycoproteins in humans an", "in humans an erythroid", "humans an erythroid specific", "an erythroid specific rh associated", "erythroid specific rh associated glycoprotein", "rh associated glycoprotein rhag", "glycoprotein rhag and", "rhag and two non", "and two non erythroid rh", "two non erythroid rh glycoproteins", "erythroid rh glycoproteins rhbg", "rh glycoproteins rhbg and", "glycoproteins rhbg and rhcg.", "rhbg and rhcg. these proteins", "and rhcg. these proteins are", "rhcg. these proteins are related", "these proteins are related to", "proteins are related to ammonium", "related to ammonium nh4+", "ammonium nh4+ transporters", "nh4+ transporters of yeast", "transporters of yeast and bacteria", "yeast and bacteria methylammonium", "and bacteria methylammonium and", "bacteria methylammonium and ammonium", "methylammonium and ammonium permease and", "and ammonium permease and ammonium", "ammonium permease and ammonium transporter", "and ammonium transporter mep/amt", "mep/amt nakhoul nl", "nakhoul nl and hamm ll", "and hamm ll 2004", "ll 2004 planelles", "planelles g 2007 ." ] }, { "record_id": "GLY_000594_1_1666", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "446199", "r hsa", "hsa 446199", "r hsa 446199" ] }, { "record_id": "GLY_000594_1_1666", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "synthesis of", "of dolichyl", "dolichyl phosphate", "synthesis of dolichyl", "of dolichyl phosphate", "synthesis of dolichyl phosphate", "dolichol is", "is a", "a polyisoprenol", "polyisoprenol lipid", "lipid comprised", "comprised of", "of five", "five carbon", "carbon isoprene", "isoprene units", "units linked", "linked linearly", "linearly in", "in a", "a head", "head to", "to tail", "tail fashion.", "fashion. almost", "almost all", "all eukaryotic", "eukaryotic membranes", "membranes contain", "contain dolichol", "dolichol and", "and its", "its phosphorylated", "phosphorylated form", "form is", "is used", "used in", "in the", "the n", "n glycosylation", "glycosylation of", "of proteins", 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"the end of n glycan", "end of n glycan biosynthesis", "n glycan biosynthesis cantagrel", "glycan biosynthesis cantagrel &", "biosynthesis cantagrel & lefeber", "cantagrel & lefeber 2011 ." ] }, { "record_id": "GLY_000594_1_1667", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "448424", "r hsa", "hsa 448424", "r hsa 448424" ] }, { "record_id": "GLY_000594_1_1667", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 17", "17 signaling", "interleukin 17 signaling", "is a", "a family", "family of", "of cytokines", "kawaguchi et", "et al.", "al. 2004", "gu et", "al. 2013", "2013 .", ". il17a", "the founding", "founding member", "member of", "of the", "the family", "family is", "is able", "able to", "to induce", "induce the", "the production", "production of", "of other", "other cytokines", "cytokines and", "and chemokines", "such as", "as il6", "and granulocyte", "granulocyte colony", 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"stabilize the", "the mrna", "mrna of", "of genes", "genes induced", "induced by", "by tnf", "tnf alpha.", "alpha. il17", "il17 signal", "signal transduction", "transduction is", "is mediated", "mediated by", "by the", "the cytosolic", "cytosolic adaptor", "adaptor molecule", "molecule act1", "also known", "known as", "as ciks", "ciks .

              the", ".

              the receptor", "receptor for", "for il17d", "il17d is", "is unknown", "17 il17", "il17 is", "is a family", "a family of", "family of cytokines", "cytokines kawaguchi", "kawaguchi et al.", "et al. 2004", "2004 gu", "gu et al.", "et al. 2013", "al. 2013 .", "2013 . il17a", "il17a the", "the founding member", "founding member of", "member of the", "of the family", "the family is", "family is able", "is able to", "able to induce", "to induce the", "induce the production", "the production of", "production of other", "of other cytokines", "other cytokines and", "cytokines and chemokines", "chemokines such", "such as il6", "il6 il8", "il8 and", "and granulocyte colony", "granulocyte colony stimulating", "colony stimulating factor", "factor g", "csf in", "in a variety", "a variety of", "variety of cell", "of cell types", "types including", "including activated t", "activated t cells.", "t cells. it", "cells. it plays", "it plays a", "plays a pivotal", "a pivotal role", "pivotal role in", "role in host", "in host defenses", "host defenses in", "defenses in response", "in response to", "response to microbial", "to microbial infection", "microbial infection and", "infection and is", "and is involved", "is involved in", "involved in the", "in the pathogenesis", "the pathogenesis of", "pathogenesis of autoimmune", "of autoimmune diseases", "autoimmune diseases and", "diseases and allergic", "and allergic syndromes.", "allergic syndromes. il17", "syndromes. il17 activates", "il17 activates several", "activates several downstream", "several downstream signaling", "downstream signaling pathways", "signaling pathways including", "pathways including nfkb", "nfkb mapks", "mapks and c/ebps", "c/ebps inducing", "inducing the expression", "the expression of", "expression of antibacterial", "of antibacterial peptides", "peptides proinflammatory", "proinflammatory chemokines and", "chemokines and cytokines", "and cytokines and", "cytokines and matrix", "and matrix metalloproteases", "metalloproteases mmps", "mmps . il17", ". il17 can", "il17 can stabilize", "can stabilize the", "stabilize the mrna", "the mrna of", "mrna of genes", "of genes induced", "genes induced by", "induced by tnf", "by tnf alpha.", "tnf alpha. il17", "alpha. il17 signal", "il17 signal transduction", "signal transduction is", "transduction is mediated", "is mediated by", "mediated by the", "by the cytosolic", "the cytosolic adaptor", "cytosolic adaptor molecule", "adaptor molecule act1", "act1 also", "also known as", "known as ciks", "as ciks .

              the", "ciks .

              the receptor", ".

              the receptor for", "receptor for il17d", "for il17d is", "il17d is unknown", "unknown gu", "interleukin 17 il17", "il17 is a", "is a family of", "a family of cytokines", "of cytokines kawaguchi", "cytokines kawaguchi et", "kawaguchi et al. 2004", "al. 2004 gu", "2004 gu et", "gu et al. 2013", "et al. 2013 .", "al. 2013 . il17a", ". il17a the", "il17a the founding", "the founding member of", "founding member of the", "member of the family", "of the family is", "the family is able", "family is able to", "is able to induce", "able to induce the", "to induce the production", "induce the production of", "the production of other", "production of other cytokines", "of other cytokines and", "other cytokines and chemokines", "and chemokines such", "chemokines such as", "as il6 il8", "il8 and granulocyte", "and granulocyte colony stimulating", "granulocyte colony stimulating factor", "stimulating factor g", "factor g csf", "g csf in", "csf in a", "in a variety of", "a variety of cell", "variety of cell types", "cell types including", "types including activated", "including activated t cells.", "activated t cells. it", "t cells. it plays", "cells. it plays a", "it plays a pivotal", "plays a pivotal role", "a pivotal role in", "pivotal role in host", "role in host defenses", "in host defenses in", "host defenses in response", "defenses in response to", "in response to microbial", "response to microbial infection", "to microbial infection and", "microbial infection and is", "infection and is involved", "and is involved in", "is involved in the", "involved in the pathogenesis", "in the pathogenesis of", "the pathogenesis of autoimmune", "pathogenesis of autoimmune diseases", "of autoimmune diseases and", "autoimmune diseases and allergic", "diseases and allergic syndromes.", "and allergic syndromes. il17", "allergic syndromes. il17 activates", "syndromes. il17 activates several", "il17 activates several downstream", "activates several downstream signaling", "several downstream signaling pathways", "downstream signaling pathways including", "signaling pathways including nfkb", "including nfkb mapks", "nfkb mapks and", "and c/ebps inducing", "c/ebps inducing the", "inducing the expression of", "the expression of antibacterial", "expression of antibacterial peptides", "antibacterial peptides proinflammatory", "peptides proinflammatory chemokines", "proinflammatory chemokines and cytokines", "chemokines and cytokines and", "and cytokines and matrix", "cytokines and matrix metalloproteases", "matrix metalloproteases mmps", "metalloproteases mmps .", "mmps . il17 can", ". il17 can stabilize", "il17 can stabilize the", "can stabilize the mrna", "stabilize the mrna of", "the mrna of genes", "mrna of genes induced", "of genes induced by", "genes induced by tnf", "induced by tnf alpha.", "by tnf alpha. il17", "tnf alpha. il17 signal", "alpha. il17 signal transduction", "il17 signal transduction is", "signal transduction is mediated", "transduction is mediated by", "is mediated by the", "mediated by the cytosolic", "by the cytosolic adaptor", "the cytosolic adaptor molecule", "cytosolic adaptor molecule act1", "molecule act1 also", "act1 also known", "also known as ciks", "known as ciks .

              the", "as ciks .

              the receptor", "ciks .

              the receptor for", ".

              the receptor for il17d", "receptor for il17d is", "for il17d is unknown", "is unknown gu", "unknown gu et", "17 il17 is", "il17 is a family", "is a family of cytokines", "family of cytokines kawaguchi", "of cytokines kawaguchi et", "cytokines kawaguchi et al.", "et al. 2004 gu", "al. 2004 gu et", "2004 gu et al.", "gu et al. 2013 .", "et al. 2013 . il17a", "2013 . il17a the", ". il17a the founding", "il17a the founding member", "the founding member of the", "founding member of the family", "member of the family is", "of the family is able", "the family is able to", "family is able to induce", "is able to induce the", "able to induce the production", "to induce the production of", "induce the production of other", "the production of other cytokines", "production of other cytokines and", "of other cytokines and chemokines", "cytokines and chemokines such", "and chemokines such as", "chemokines such as il6", "such as il6 il8", "il6 il8 and", "il8 and granulocyte colony", "and granulocyte colony stimulating factor", "colony stimulating factor g", "stimulating factor g csf", "g csf in a", "csf in a variety", "in a variety of cell", "a variety of cell types", "of cell types including", "cell types including activated", "types including activated t", "including activated t cells. it", "activated t cells. it plays", "t cells. it plays a", "cells. it plays a pivotal", "it plays a pivotal role", "plays a pivotal role in", "a pivotal role in host", "pivotal role in host defenses", "role in host defenses in", "in host defenses in response", "host defenses in response to", "defenses in response to microbial", "in response to microbial infection", "response to microbial infection and", "to microbial infection and is", "microbial infection and is involved", "infection and is involved in", "and is involved in the", "is involved in the pathogenesis", "involved in the pathogenesis of", "in the pathogenesis of autoimmune", "the pathogenesis of autoimmune diseases", "pathogenesis of autoimmune diseases and", "of autoimmune diseases and allergic", "autoimmune diseases and allergic syndromes.", "diseases and allergic syndromes. il17", "and allergic syndromes. il17 activates", "allergic syndromes. il17 activates several", "syndromes. il17 activates several downstream", "il17 activates several downstream signaling", "activates several downstream signaling pathways", "several downstream signaling pathways including", "downstream signaling pathways including nfkb", "pathways including nfkb mapks", "including nfkb mapks and", "nfkb mapks and c/ebps", "mapks and c/ebps inducing", "and c/ebps inducing the", "c/ebps inducing the expression", "inducing the expression of antibacterial", "the expression of antibacterial peptides", "of antibacterial peptides proinflammatory", "antibacterial peptides proinflammatory chemokines", "peptides proinflammatory chemokines and", "proinflammatory chemokines and cytokines and", "chemokines and cytokines and matrix", "and cytokines and matrix metalloproteases", "and matrix metalloproteases mmps", "matrix metalloproteases mmps .", "metalloproteases mmps . il17", "mmps . il17 can stabilize", ". il17 can stabilize the", "il17 can stabilize the mrna", "can stabilize the mrna of", "stabilize the mrna of genes", "the mrna of genes induced", "mrna of genes induced by", "of genes induced by tnf", "genes induced by tnf alpha.", "induced by tnf alpha. il17", "by tnf alpha. il17 signal", "tnf alpha. il17 signal transduction", "alpha. il17 signal transduction is", "il17 signal transduction is mediated", "signal transduction is mediated by", "transduction is mediated by the", "is mediated by the cytosolic", "mediated by the cytosolic adaptor", "by the cytosolic adaptor molecule", "the cytosolic adaptor molecule act1", "adaptor molecule act1 also", "molecule act1 also known", "act1 also known as", "also known as ciks .

              the", "known as ciks .

              the receptor", "as ciks .

              the receptor for", "ciks .

              the receptor for il17d", ".

              the receptor for il17d is", "receptor for il17d is unknown", "il17d is unknown gu", "is unknown gu et", "unknown gu et al." ] }, { "record_id": "GLY_000594_1_1668", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "450385", "r hsa", "hsa 450385", "r hsa 450385" ] }, { "record_id": "GLY_000594_1_1668", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "butyrate response", "response factor", "factor 1", "binds and", "and destabilizes", "destabilizes mrna", "butyrate response factor", "response factor 1", "1 brf1", "brf1 binds", "binds and destabilizes", "and destabilizes mrna", "butyrate response factor 1", "factor 1 brf1", "brf1 binds and", "binds and destabilizes mrna", "response factor 1 brf1", "1 brf1 binds", "brf1 binds and destabilizes", "not to", "to be", "be confused", "confused with", "with transcription", "transcription factor", "factor iiib", "binds au", "au rich", "rich 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"passage of na+ ions.", "of na+ ions. glutamine", "na+ ions. glutamine in", "ions. glutamine in grik1", "glutamine in grik1 at", "in grik1 at position", "grik1 at position 636", "at position 636 is", "position 636 is replaced", "636 is replaced by", "is replaced by arginine", "replaced by arginine by", "by arginine by an", "arginine by an editing", "by an editing step", "an editing step which", "editing step which occurs", "step which occurs posttranscriptioanlly.", "which occurs posttranscriptioanlly. grik2", "occurs posttranscriptioanlly. grik2 is", "posttranscriptioanlly. grik2 is glutamine", "grik2 is glutamine 621", "is glutamine 621 is", "glutamine 621 is edited", "621 is edited to", "is edited to arginine.", "edited to arginine. grik2", "to arginine. grik2 is", "arginine. grik2 is also", "grik2 is also edited", "is also edited at", "also edited at 571", "at 571 y/c", "y/c where", "where a tyrosine residue", "a tyrosine residue is", "tyrosine residue is changed", "residue is 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edited at", "that are edited at the", "are edited at the q/r", "edited at the q/r and", "at the q/r and other", "the q/r and other editing", "q/r and other editing sites", "and other editing sites in", "other editing sites in grik2", "editing sites in grik2 are", "sites in grik2 are ca2+", "in grik2 are ca2+ impermeable.", "grik2 are ca2+ impermeable. they", "are ca2+ impermeable. they permit", "ca2+ impermeable. they permit the", "impermeable. they permit the passage", "they permit the passage of", "permit the passage of na+", "the passage of na+ ions.", "passage of na+ ions. glutamine", "of na+ ions. glutamine in", "na+ ions. glutamine in grik1", "ions. glutamine in grik1 at", "glutamine in grik1 at position", "in grik1 at position 636", "grik1 at position 636 is", "at position 636 is replaced", "position 636 is replaced by", "636 is replaced by arginine", "is replaced by arginine by", "replaced by arginine by an", "by arginine by an editing", "arginine by an editing step", "by an editing step which", "an editing step which occurs", "editing step which occurs posttranscriptioanlly.", "step which occurs posttranscriptioanlly. grik2", "which occurs posttranscriptioanlly. grik2 is", "occurs posttranscriptioanlly. grik2 is glutamine", "posttranscriptioanlly. grik2 is glutamine 621", "grik2 is glutamine 621 is", "is glutamine 621 is edited", "glutamine 621 is edited to", "621 is edited to arginine.", "is edited to arginine. grik2", "edited to arginine. grik2 is", "to arginine. grik2 is also", "arginine. grik2 is also edited", "grik2 is also edited at", "is also edited at 571", "edited at 571 y/c", "y/c where a", "where a tyrosine residue is", "a tyrosine residue is changed", "tyrosine residue is changed to", "residue is changed to cysteine", "is changed to cysteine and", "changed to cysteine and 567", "cysteine and 567 i/v", "567 i/v where", "i/v where an isoleucine", "where an isoleucine is changed", "an isoleucine is changed to", "isoleucine is changed to valine.", "is changed to valine. all", "changed to valine. all three", "to valine. all three sites", "valine. all three sites are", "all three sites are edited", "sites are edited postranscriptionally.", "are edited postranscriptionally. a", "edited postranscriptionally. a fully", "postranscriptionally. a fully edited grik2", "a fully edited grik2 at", "fully edited grik2 at all", "edited grik2 at all three", "grik2 at all three sites", "at all three sites is", "three sites is impermeable", "sites is impermeable to", "is impermeable to calcium" ] }, { "record_id": "GLY_000594_1_1670", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4549349", "r hsa", "hsa 4549349", "r hsa 4549349" ] }, { "record_id": "GLY_000594_1_1670", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective alg2", "alg2 causes", "causes cdg", "cdg 1i", "defective alg2 causes", "alg2 causes cdg", "causes cdg 1i", "defective alg2 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"type 1", "1 diseases", "diseases result", "result in", "in a", "a wide", "wide phenotypic", "phenotypic spectrum", "from poor", "poor neurological", "neurological development", "psychomotor retardation", "retardation and", "and dysmorphic", "dysmorphic features", "features to", "to hypotonia", "coagulation abnormalities", "abnormalities and", "and immunodeficiency", "thiel et", "et al.", "al. 2003", "2003 .", ". defect", "defect in", "can also", "also cause", "congenital myasthenic", "myasthenic syndrome", "alg2 cms", "is due", "due to", "to a", "a defect", "in neuromuscular", "neuromuscular signal", "signal transmission", "cossins et", "al. 2013", "2013 .", ". the", "the most", "most commonly", "commonly affected", "affected muscles", "muscles include", "include proximal", "proximal limb", "limb muscles.", "muscles. mutations", "mutations causing", "causing alg2", "cms include", "include p.v68g", "p.v68g and", "and p.72_75delinsspr", "alpha 1 3/1", "1 3/1 6", "3/1 6 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"limb muscles. mutations causing alg2", "muscles. mutations causing alg2 cms", "mutations causing alg2 cms include", "causing alg2 cms include p.v68g", "alg2 cms include p.v68g and", "cms include p.v68g and p.72_75delinsspr", "p.v68g and p.72_75delinsspr cossins", "and p.72_75delinsspr cossins et", "p.72_75delinsspr cossins et al." ] }, { "record_id": "GLY_000594_1_1671", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4549356", "r hsa", "hsa 4549356", "r hsa 4549356" ] }, { "record_id": "GLY_000594_1_1671", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective dpagt1", "dpagt1 causes", "causes cdg", "cdg 1j", "defective dpagt1 causes", "dpagt1 causes cdg", "causes cdg 1j", "1j cmsta2", "defective dpagt1 causes cdg", "dpagt1 causes cdg 1j", "cdg 1j cmsta2", "defective dpagt1 causes cdg 1j", "causes cdg 1j cmsta2", "udp n", "n acetylglucosamine", "dolichyl phosphate", "phosphate n", "n 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by under", "disorder characterised by under glycosylated", "characterised by under glycosylated serum", "by under glycosylated serum glycoproteins", "glycosylated serum glycoproteins wu", "serum glycoproteins wu et", "glycoproteins wu et al.", "et al. 2003 timal", "al. 2003 timal et", "2003 timal et al.", "timal et al. 2012 .", "et al. 2012 . congenital", "al. 2012 . congenital disorders", "2012 . congenital disorders of", ". congenital disorders of glycosylation", "congenital disorders of glycosylation result", "disorders of glycosylation result in", "of glycosylation result in a", "glycosylation result in a wide", "result in a wide variety", "in a wide variety of", "a wide variety of clinical", "wide variety of clinical features", "of clinical features such", "clinical features such as", "features such as defects", "such as defects in the", "as defects in the nervous", "defects in the nervous system", "in the nervous system development", "nervous system development psychomotor", "system development psychomotor retardation", "psychomotor retardation dysmorphic features", "features hypotonia coagulation", "coagulation disorders and immunodeficiency.", "disorders and immunodeficiency. defects", "and immunodeficiency. defects in dpagt1", "immunodeficiency. defects in dpagt1 can", "defects in dpagt1 can also", "in dpagt1 can also cause", "dpagt1 can also cause myasthenic", "can also cause myasthenic syndrome", "cause myasthenic syndrome congenital", "syndrome congenital with", "congenital with tubular aggregates", "with tubular aggregates 2", "aggregates 2 cmsta2", "2 cmsta2 mim:614750", "mim:614750 characterised by", "614750 characterised by", "characterised by muscle weakness of", "by muscle weakness of mainly", "muscle weakness of mainly the", "weakness of mainly the proximal", "of mainly the proximal limb", "mainly the proximal limb muscles", "proximal limb muscles with", "limb muscles with tubular", "muscles with tubular aggregates", "with tubular aggregates present on", "tubular aggregates present on muscle", "aggregates present on muscle biopsy.", "present on muscle biopsy. sufferers", "on muscle biopsy. sufferers find", "muscle biopsy. sufferers find walking", "biopsy. sufferers find walking difficult", "sufferers find walking difficult and", "find walking difficult and fall", "walking difficult and fall frequently.", "difficult and fall frequently. younger", "and fall frequently. younger sufferers", "fall frequently. younger sufferers show", "frequently. younger sufferers show hypotonia", "younger sufferers show hypotonia and", "sufferers show hypotonia and poor", "show hypotonia and poor head", "hypotonia and poor head control.", "and poor head control. a", "poor head control. a disorder", "head control. a disorder of", "control. a disorder of neuromuscular", "a disorder of neuromuscular transmission", "disorder of neuromuscular transmission is", "of neuromuscular transmission is detected", "neuromuscular transmission is detected on", "transmission is detected on electromyography", "detected on electromyography belaya", "on electromyography belaya et", "electromyography belaya et al.", "et al. 2012 finlayson", "al. 2012 finlayson et", "2012 finlayson et al.", "finlayson et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1672", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4549380", "r hsa", "hsa 4549380", "r hsa 4549380" ] }, { "record_id": "GLY_000594_1_1672", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective alg1", "alg1 causes", "causes cdg", "cdg 1k", "defective alg1 causes", "alg1 causes cdg", "causes cdg 1k", "defective alg1 causes cdg", "alg1 causes cdg 1k", "defective alg1 causes cdg 1k", "chitobiosyldiphosphodolichol beta", "beta mannosyltransferase", "normally tranfers", "tranfers a", "a mannose", "mannose moiety", "moiety to", "to the", "the lipid", "lipid linked", "linked oligosaccharide", "llo aka", "aka 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in the nervous system", "in the nervous system development", "nervous system development psychomotor", "system development psychomotor retardation", "psychomotor retardation dysmorphic features", "features hypotonia coagulation", "coagulation disorders and immunodeficiency." ] }, { "record_id": "GLY_000594_1_1679", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4724289", "r hsa", "hsa 4724289", "r hsa 4724289" ] }, { "record_id": "GLY_000594_1_1679", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective alg6", "alg6 causes", "causes cdg", "cdg 1c", "defective alg6 causes", "alg6 causes cdg", "causes cdg 1c", "defective alg6 causes cdg", "alg6 causes cdg 1c", "defective alg6 causes cdg 1c", "dolichyl pyrophosphate", "pyrophosphate man9glcnac2", "man9glcnac2 alpha", "alpha 1", "1 3", "3 glucosyltransferase", "normally adds", "adds the", "the first", "first glucose", "glucose moiety", "moiety 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}, { "record_id": "GLY_000594_1_1683", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective dhdds", "dhdds causes", "causes rp59", "defective dhdds causes", "dhdds causes rp59", "defective dhdds causes rp59", "the er", "er membrane", "membrane associated", "associated enzyme", "enzyme dehydrodolichyl", "dehydrodolichyl diphosphate", "diphosphate synthase", "endo et", "et al.", "al. 2003", "normally mediates", "mediates the", "the sequential", "sequential head", "head to", "to tail", "tail cis", "cis addition", "addition of", "of multiple", "multiple isopentyl", "isopentyl pyrophosphate", "molecules to", "to farnesyl", "farnesyl pyrophosphate", "e e", "e fpp", "to produce", "produce polyprenol", "polyprenol pyrophosphate", "shridas et", "2003 .", ". dolichol", "dolichol in", "in humans", "humans contain", "contain homologues", "homologues ranging", "ranging from", "from 17", "17 23", "23 isoprene", "isoprene units", "the most", "most common", 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              defects", "rhodopsin.

              defects in", "in dhdds", "dhdds cause", "cause retinitis", "retinitis pigmentosa", "pigmentosa 59", "a pigment", "pigment retinopathy", "characterised by", "by retinal", "retinal pigment", "pigment deposits", "visible on", "on fundus", "fundus examination", "and primary", "primary loss", "loss of", "of rod", "rod photoreceptors", "photoreceptors followed", "followed by", "by secondary", "secondary loss", "of cone", "cone photoreceptors.", "photoreceptors. sufferers", "sufferers typically", "typically have", "have night", "night vision", "vision blindness", "blindness and", "and loss", "of mid", "mid to", "to peripheral", "peripheral vision.", "vision. as", "as the", "the condition", "condition progresses", "they lose", "lose far", "far peripheral", "peripheral vision", "vision and", "and eventually", "eventually central", "central vision", "zuchner et", "al. 2011", "2011 .", "the er membrane", "er membrane associated", "membrane associated enzyme", "associated enzyme dehydrodolichyl", "enzyme dehydrodolichyl diphosphate", "dehydrodolichyl diphosphate synthase", "synthase dhdds", "endo et al.", "et al. 2003", "2003 normally", "normally mediates the", "mediates the sequential", "the sequential head", "sequential head to", "head to tail", "to tail cis", "tail cis addition", "cis addition of", "addition of multiple", "of multiple isopentyl", "multiple isopentyl pyrophosphate", "pyrophosphate ipp", "ipp molecules", "molecules to farnesyl", "to farnesyl pyrophosphate", "pyrophosphate e", "e e fpp", "fpp to", "to produce polyprenol", "produce polyprenol pyrophosphate", "pyrophosphate pppp", "shridas et al.", "al. 2003 .", "2003 . dolichol", ". dolichol in", "dolichol in humans", "in humans contain", "humans contain homologues", "contain homologues ranging", "homologues ranging from", "ranging from 17", "from 17 23", "17 23 isoprene", "23 isoprene units", "units the", "the most common", "most common homologues", "common homologues contain", "homologues contain 19", "contain 19 or", "19 or 20", "or 20 isoprene", "20 isoprene units", "units freeman", "freeman et al.", "et al. 1980", "al. 1980 .", "1980 . dolichol", ". dolichol is", "dolichol is an", "is an important", "an important substrate", "important substrate in", "substrate in the", "in the n", "the n glycosylation", "n glycosylation of", "glycosylation of proteins", "proteins including", "including rhodopsin.

              defects in", "rhodopsin.

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              defects", "including rhodopsin.

              defects in dhdds", "rhodopsin.

              defects in dhdds cause", "in dhdds cause retinitis", "dhdds cause retinitis pigmentosa", "cause retinitis pigmentosa 59", "pigmentosa 59 rp59", "mim:613861 a", "613861 a", "pigment retinopathy characterised", "retinopathy characterised by", "characterised by retinal pigment", "by retinal pigment deposits", "pigment deposits visible", "deposits visible on", "visible on fundus examination", "fundus examination and", "examination and primary", "and primary loss of", "primary loss of rod", "loss of rod photoreceptors", "of rod photoreceptors followed", "rod photoreceptors followed by", "photoreceptors followed by secondary", "followed by secondary loss", "by secondary loss of", "secondary loss of cone", "loss of cone photoreceptors.", "of cone photoreceptors. sufferers", "cone photoreceptors. sufferers typically", "photoreceptors. sufferers typically have", "sufferers typically have night", "typically have night vision", "have night vision blindness", "night vision blindness and", "vision blindness and loss", "blindness and loss of", "and loss of mid", "loss of mid to", "of mid to peripheral", "mid to peripheral vision.", "to peripheral vision. as", "peripheral vision. as the", "vision. as the condition", "as the condition progresses", "condition progresses they", "progresses they lose", "they lose far peripheral", "lose far peripheral vision", "far peripheral vision and", "peripheral vision and eventually", "vision and eventually central", "and eventually central vision", "central vision zuchner", "vision zuchner et", "zuchner et al. 2011", "et al. 2011 .", "the er membrane associated enzyme", "er membrane associated enzyme dehydrodolichyl", "membrane associated enzyme dehydrodolichyl diphosphate", "associated enzyme dehydrodolichyl diphosphate synthase", "dehydrodolichyl diphosphate synthase dhdds", "dhdds endo et", "et al. 2003 normally", "al. 2003 normally mediates", "2003 normally mediates the", "normally mediates the sequential head", "mediates the sequential head to", "the sequential head to tail", "sequential head to tail cis", "head to tail cis addition", "to tail cis addition of", "tail cis addition of multiple", "cis addition of multiple isopentyl", "addition of multiple isopentyl pyrophosphate", "multiple isopentyl pyrophosphate ipp", "pyrophosphate ipp molecules", "ipp molecules to farnesyl", "to farnesyl pyrophosphate e", "farnesyl pyrophosphate e e", "pyrophosphate e e fpp", "e e fpp to", "e fpp to produce", "fpp to produce polyprenol", "produce polyprenol pyrophosphate pppp", "pppp shridas et", "shridas et al. 2003 .", "et al. 2003 . dolichol", "al. 2003 . dolichol in", "2003 . dolichol in humans", ". dolichol in humans contain", "dolichol in humans contain homologues", "in humans contain homologues ranging", "humans contain homologues ranging from", "contain homologues ranging from 17", "homologues ranging from 17 23", "ranging from 17 23 isoprene", "from 17 23 isoprene units", "23 isoprene units the", "isoprene units the most", "units the most common", "the most common homologues contain", "most common homologues contain 19", "common homologues contain 19 or", "homologues contain 19 or 20", "contain 19 or 20 isoprene", "19 or 20 isoprene units", "20 isoprene units freeman", "isoprene units freeman et", "units freeman et al.", "freeman et al. 1980 .", "et al. 1980 . dolichol", "al. 1980 . dolichol is", "1980 . dolichol is an", ". dolichol is an important", "dolichol is an important substrate", "is an important substrate in", "an important substrate in the", "important substrate in the n", "substrate in the n glycosylation", "in the n glycosylation of", "the n glycosylation of proteins", "glycosylation of proteins including", "of proteins including rhodopsin.

              defects", "proteins including rhodopsin.

              defects in", "including rhodopsin.

              defects in dhdds cause", "rhodopsin.

              defects in dhdds cause retinitis", "in dhdds cause retinitis pigmentosa", "dhdds cause retinitis pigmentosa 59", "retinitis pigmentosa 59 rp59", "59 rp59 mim:613861", "mim:613861 a pigment", "613861 a pigment", "a pigment retinopathy characterised", "pigment retinopathy characterised by", "retinopathy characterised by retinal", "characterised by retinal pigment deposits", "retinal pigment deposits visible", "pigment deposits visible on", "deposits visible on fundus", "on fundus examination and", "fundus examination and primary", "examination and primary loss", "and primary loss of rod", "primary loss of rod photoreceptors", "loss of rod photoreceptors followed", "of rod photoreceptors followed by", "rod photoreceptors followed by secondary", "photoreceptors followed by secondary loss", "followed by secondary loss of", "by secondary loss of cone", "secondary loss of cone photoreceptors.", "loss of cone photoreceptors. sufferers", "of cone photoreceptors. sufferers typically", "cone photoreceptors. sufferers typically have", "photoreceptors. sufferers typically have night", "sufferers typically have night vision", "typically have night vision blindness", "have night vision blindness and", "night vision blindness and loss", "vision blindness and loss of", "blindness and loss of mid", "and loss of mid to", "loss of mid to peripheral", "of mid to peripheral vision.", "mid to peripheral vision. as", "to peripheral vision. as the", "peripheral vision. as the condition", "vision. as the condition progresses", "the condition progresses they", "condition progresses they lose", "progresses they lose far", "they lose far peripheral vision", "lose far peripheral vision and", "far peripheral vision and eventually", "peripheral vision and eventually central", "vision and eventually central vision", "eventually central vision zuchner", "central vision zuchner et", "vision zuchner et al.", "zuchner et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1684", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "4793950", "r hsa", "hsa 4793950", "r hsa 4793950" ] }, { "record_id": "GLY_000594_1_1684", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective man1b1", "man1b1 causes", "causes mrt15", "defective man1b1 causes", "man1b1 causes mrt15", "defective man1b1 causes mrt15", "endoplasmic reticulum", "reticulum mannosyl", "mannosyl oligosaccharide", "oligosaccharide 1", "1 2", "2 alpha", "alpha mannosidase", "normally trims", "trims single", "single mannose", "mannose residues", "residues from", "from misfolded", "misfolded glycoproteins", "targeting them", "them for", "for degradation", "degradation and", "and thus", "thus providing", "providing a", "a quality", "quality control", "control process", "process for", "for n", "n glycoyslated", "glycoyslated proteins.", "proteins. defects", "defects in", "in man1b1", "man1b1 can", "can cause", "cause 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cormier", "cormier daire et al.", "daire et al. 2000", "2000 alkuraya", "alkuraya 2010 alazami", "2010 alazami et", "alazami et al. 2012", "et al. 2012 .", "al. 2012 . type", "2012 . type ii", ". type ii cdgs", "type ii cdgs refer", "ii cdgs refer to", "cdgs refer to defects", "refer to defects in", "to defects in the", "defects in the trimming", "in the trimming and", "the trimming and processing", "trimming and processing of", "and processing of protein", "processing of protein bound", "of protein bound glycans.", "alpha 1 6 mannosyl glycoprotein", "1 6 mannosyl glycoprotein 2", "6 mannosyl glycoprotein 2 beta", "mannosyl glycoprotein 2 beta n", "glycoprotein 2 beta n acetylglucosaminyltransferase", "beta n acetylglucosaminyltransferase mgat2", "acetylglucosaminyltransferase mgat2 normally", "mgat2 normally catalyses the", "normally catalyses the transfer of", "catalyses the transfer of a", "the transfer of a glcnac", "transfer of a glcnac moiety", "of a glcnac moiety onto", "a 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caused by a", "disorder caused by a defect", "caused by a defect in", "by a defect in glycoprotein", "a defect in glycoprotein biosynthesis", "defect in glycoprotein biosynthesis and", "in glycoprotein biosynthesis and characterised", "glycoprotein biosynthesis and characterised by", "biosynthesis and characterised by under", "and characterised by under glycosylated", "characterised by under glycosylated serum", "by under glycosylated serum glycoproteins", "glycosylated serum glycoproteins de", "serum glycoproteins de praeter", "glycoproteins de praeter et", "de praeter et al. 2000", "et al. 2000 voelker", "al. 2000 voelker et", "2000 voelker et al.", "voelker et al. 2002 .", "et al. 2002 . type", "al. 2002 . type ii", "2002 . type ii cdgs", ". type ii cdgs refer", "type ii cdgs refer to", "ii cdgs refer to defects", "cdgs refer to defects in", "refer to defects in the", "to defects in the trimming", "defects in the trimming and", "in the trimming and processing", "the trimming and processing of", "trimming and processing of protein", "and processing of protein bound", "processing of protein bound glycans." ] }, { "record_id": "GLY_000594_1_1687", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5083628", "r hsa", "hsa 5083628", "r hsa 5083628" ] }, { "record_id": "GLY_000594_1_1687", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pomgnt1", "pomgnt1 causes", "causes mddga3", "mddgb3 and", "and mddgc3", "defective pomgnt1 causes", "pomgnt1 causes mddga3", "mddga3 mddgb3", "mddgb3 and mddgc3", "defective pomgnt1 causes mddga3", "causes mddga3 mddgb3", "mddga3 mddgb3 and", "pomgnt1 causes mddga3 mddgb3", "causes mddga3 mddgb3 and", "mddga3 mddgb3 and mddgc3", "protein o", "o linked", "linked mannose", "mannose beta", "beta 1", "1 2", "2 n", "n acetylglucosaminyltransferase", "acetylglucosaminyltransferase 1", "cazy family", "family gt61", "mediates the", "the 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              the", ".

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              the", "2000 .

              the spondylocostal", ".

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              the", "al. 2000 .

              the spondylocostal", "2000 .

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              the", "et al. 2000 .

              the spondylocostal", "al. 2000 .

              the spondylocostal dysostoses", ".

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"of vertebra and associated musculature.", "vertebra and associated musculature. defects", "and associated musculature. defects in", "associated musculature. defects in one", "musculature. defects in one of", "defects in one of the", "in one of the fringe", "one of the fringe enzymes", "the fringe enzymes beta", "fringe enzymes beta 1", "enzymes beta 1 3", "beta 1 3 n acetylglucosaminyltransferase", "1 3 n acetylglucosaminyltransferase lunatic", "3 n acetylglucosaminyltransferase lunatic fringe", "acetylglucosaminyltransferase lunatic fringe lfng", "lfng can cause", "cause spondylocostal dysostosis autosomal", "spondylocostal dysostosis autosomal recessive", "dysostosis autosomal recessive 3", "autosomal recessive 3 scdo3", "3 scdo3 mim:609813", "mim:609813 a condition", "609813 a condition", "a condition of variable severity", "condition of variable severity associated", "of variable severity associated with", "variable severity associated with vertebral", "severity associated with vertebral and", "associated with vertebral and rib", "with vertebral and rib segmentation", "vertebral and rib segmentation defects", "rib segmentation defects sparrow", "segmentation defects sparrow et", "defects sparrow et al.", "sparrow et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1690", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5083633", "r hsa", "hsa 5083633", "r hsa 5083633" ] }, { "record_id": "GLY_000594_1_1690", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pomt1", "pomt1 causes", "causes mddga1", "mddgb1 and", "and mddgc1", "defective pomt1 causes", "pomt1 causes mddga1", "mddga1 mddgb1", "mddgb1 and mddgc1", "defective pomt1 causes mddga1", "causes mddga1 mddgb1", "mddga1 mddgb1 and", "pomt1 causes mddga1 mddgb1", "causes mddga1 mddgb1 and", "mddga1 mddgb1 and mddgc1", "co expression", "expression of", "of both", "both protein", "protein o", "o mannosyl", 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              defects", "s methylation.

              defects in", "methylation.

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              defects in", "s methylation.

              defects in tpmt", "methylation.

              defects in tpmt can", "in tpmt can cause", "tpmt can cause thiopurine", "can cause thiopurine s", "cause thiopurine s methyltransferase", "thiopurine s methyltransferase deficiency", "methyltransferase deficiency tpmt", "deficiency tpmt deficiency", "tpmt deficiency mim:610460", "deficiency mim:610460 .", "mim:610460 . patients with", "610460 . patients with", ". patients with intermediate", "patients with intermediate or", "with intermediate or no", "intermediate or no tpmt", "or no tpmt activity", "no tpmt activity are", "tpmt activity are at", "activity are at risk", "are at risk of", "at risk of toxicity", "risk of toxicity such", "of toxicity such as", "toxicity such as myelosuppression", "such as myelosuppression after", "as myelosuppression after receiving", "myelosuppression after receiving standard", "after receiving standard doses", "receiving standard doses of", "standard doses of thiopurine", "doses of thiopurine drugs.", "of thiopurine drugs. inter", "thiopurine drugs. inter individual", "drugs. inter individual differences", "inter individual differences in", "individual differences in response", "differences in response to", "in response to these", "response to these drugs", "to these drugs are", "these drugs are largely", "drugs are largely determined", "are largely determined by", "largely determined by genetic", "determined by genetic variation", "by genetic variation at", "genetic variation at the", "variation at the tpmt", "at the tpmt locus.", "the tpmt locus. tpmt", "tpmt locus. tpmt exhibits", "locus. tpmt exhibits an", "tpmt exhibits an autosomal", "exhibits an autosomal co", "an autosomal co dominant", "autosomal co dominant phenotype:", "co dominant phenotype: about", "dominant phenotype: about one", "phenotype: about one in", "about one in 300", "one in 300 people", "in 300 people in", "300 people in caucasian", "in caucasian african", "african african american", "african american and", "american and asian", "and asian populations are", "asian populations are tpmt", "populations are tpmt deficient.", "are tpmt deficient. approximately", "tpmt deficient. approximately 6", "deficient. approximately 6 10%", "approximately 6 10% of", "6 10% of people", "10% of people in", "of people in these", "people in these populations", "in these populations inherit", "these populations inherit intermediate", "populations inherit intermediate tpmt", "inherit intermediate tpmt activity", "intermediate tpmt activity and", "tpmt activity and are", "activity and are heterozygous", "and are heterozygous at", "are heterozygous at the", "heterozygous at the tpmt", "the tpmt locus. the", "tpmt locus. the rest", "locus. the rest are", "the rest are homozygous", "rest are homozygous for", "are homozygous for the", "homozygous for the wild", "for the wild type", "the wild type allele", "wild type allele and", "type allele and have", "allele and have high", "and have high levels", "have high levels of", "high levels of tpmt", "levels of tpmt activity.", "tpmt activity. remy", "activity. remy 1963", "remy 1963 weinshilboum", "1963 weinshilboum et", "weinshilboum et al. 1999", "al. 1999 couldhard", "1999 couldhard &", "couldhard & hogarth 2005", "hogarth 2005 al", "2005 al hadithy", "al hadithy et al.", "hadithy et al. 2005", "al. 2005 azimi", "2005 azimi et", "azimi et al. 2014", "et al. 2014 .", "methylation is a major biotransformation", "is a major biotransformation route", "a major biotransformation route of", "major biotransformation route of thiopurine", "biotransformation route of thiopurine drugs", "route of thiopurine drugs such", "of thiopurine drugs such as", "thiopurine drugs such as 6", "drugs such as 6 mercaptopurine", "as 6 mercaptopurine 6mp", "6mp used in", "used in the treatment of", "in the treatment of inflammatory", "the treatment of inflammatory diseases", "treatment of inflammatory diseases such", "of inflammatory diseases such as", "inflammatory diseases such as rheumatoid", "diseases such as rheumatoid arthritis", "such as rheumatoid arthritis and", "as rheumatoid arthritis and childhood", "rheumatoid arthritis and childhood acute", "arthritis and childhood acute lymphoblastic", "and childhood acute lymphoblastic leukemia.", "childhood acute lymphoblastic leukemia. 6mp", "acute lymphoblastic leukemia. 6mp and", "lymphoblastic leukemia. 6mp and its", "leukemia. 6mp and its thioguanine", "6mp and its thioguanine nucleotide", "and its thioguanine nucleotide metabolites", "its thioguanine nucleotide metabolites are", "thioguanine nucleotide metabolites are principally", "nucleotide metabolites are principally inactivated", "metabolites are principally inactivated by", "are principally inactivated by thiopurine", "principally inactivated by thiopurine methyltransferase", "by thiopurine methyltransferase tpmt", "methyltransferase tpmt catalysed", "tpmt catalysed s methylation.

              defects", "catalysed s methylation.

              defects in tpmt", "s methylation.

              defects in tpmt can", "methylation.

              defects in tpmt can cause", "in tpmt can cause thiopurine", "tpmt can cause thiopurine s", "can cause thiopurine s methyltransferase", "cause thiopurine s methyltransferase deficiency", "s methyltransferase deficiency tpmt", "methyltransferase deficiency tpmt deficiency", "tpmt deficiency mim:610460 .", "deficiency mim:610460 . patients", "mim:610460 . patients with intermediate", "610460 . patients with intermediate", ". patients with intermediate or", "patients with intermediate or no", "with intermediate or no tpmt", "intermediate or no tpmt activity", "or no tpmt activity are", "no tpmt activity are at", "tpmt activity are at risk", "activity are at risk of", "are at risk of toxicity", "at risk of toxicity such", "risk of toxicity such as", "of toxicity such as myelosuppression", "toxicity such as myelosuppression after", "such as myelosuppression after receiving", "as myelosuppression after receiving standard", "myelosuppression after receiving standard doses", "after receiving standard doses of", "receiving standard doses of thiopurine", "standard doses of thiopurine drugs.", "doses of thiopurine drugs. inter", "of thiopurine drugs. inter individual", "thiopurine drugs. inter individual differences", "drugs. inter individual differences in", "inter individual differences in response", "individual differences in response to", "differences in response to these", "in response to these drugs", "response to these drugs are", "to these drugs are largely", "these drugs are largely determined", "drugs are largely determined by", "are largely determined by genetic", "largely determined by genetic variation", "determined by genetic variation at", "by genetic variation at the", "genetic variation at the tpmt", "variation at the tpmt locus.", "at the tpmt locus. tpmt", "the tpmt locus. tpmt exhibits", "tpmt locus. tpmt exhibits an", "locus. tpmt exhibits an autosomal", "tpmt exhibits an autosomal co", "exhibits an autosomal co dominant", "an autosomal co dominant phenotype:", "autosomal co dominant phenotype: about", "co dominant phenotype: about one", "dominant phenotype: about one in", "phenotype: about one in 300", "about one in 300 people", "one in 300 people in", "in 300 people in caucasian", "people in caucasian african", "caucasian african african", "african american and asian", "american and asian populations", "and asian populations are tpmt", "asian populations are tpmt deficient.", "populations are tpmt deficient. approximately", "are tpmt deficient. approximately 6", "tpmt deficient. approximately 6 10%", "deficient. approximately 6 10% of", "approximately 6 10% of people", "6 10% of people in", "10% of people in these", "of people in these populations", "people in these populations inherit", "in these populations inherit intermediate", "these populations inherit intermediate tpmt", "populations inherit intermediate tpmt activity", "inherit intermediate tpmt activity and", "intermediate tpmt activity and are", "tpmt activity and are heterozygous", "activity and are heterozygous at", "and are heterozygous at the", "are heterozygous at the tpmt", "heterozygous at the tpmt locus.", "at the tpmt locus. the", "the tpmt locus. the rest", "tpmt locus. the rest are", "locus. the rest are homozygous", "the rest are homozygous for", "rest are homozygous for the", "are homozygous for the wild", "homozygous for the wild type", "for the wild type allele", "the wild type allele and", "wild type allele and have", "type allele and have high", "allele and have high levels", "and have high levels of", "have high levels of tpmt", "high levels of tpmt activity.", "of tpmt activity. remy", "tpmt activity. remy 1963", "remy 1963 weinshilboum et", "1963 weinshilboum et al.", "et al. 1999 couldhard", "al. 1999 couldhard &", "1999 couldhard & hogarth", "& hogarth 2005 al", "hogarth 2005 al hadithy", "2005 al hadithy et", "al hadithy et al. 2005", "et al. 2005 azimi", "al. 2005 azimi et", "2005 azimi et al.", "azimi et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1698", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5578996", "r hsa", "hsa 5578996", "r hsa 5578996" ] }, { "record_id": "GLY_000594_1_1698", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cyp27a1", "cyp27a1 causes", "causes ctx", "defective cyp27a1 causes", "cyp27a1 causes ctx", "defective cyp27a1 causes ctx", "a mitochondrial", "mitochondrial matrix", "matrix sterol", "sterol hydroxylase", "catalyses the", "the 27", "27 hydroxylation", "hydroxylation of", "of side", "side chains", "chains of", "of sterol", "sterol intermediates", "cali et", "et al.", "al. 1991", "1991 .", ". in", "in the", "the bile", "bile acid", "acid synthesis", "synthesis pathway", "cyp27a1 catalyses", "the first", "first step", "step in", "the oxidation", "oxidation of", "of the", "the side", "side chain", "chain of", "intermediates such", "such as", "as 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              " ] }, { "record_id": "GLY_000594_1_1699", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5578999", "r hsa", "hsa 5578999", "r hsa 5578999" ] }, { "record_id": "GLY_000594_1_1699", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gclc", "gclc causes", "causes haggsd", "defective gclc causes", "gclc causes haggsd", "defective gclc causes haggsd", "in mammalian", "mammalian cells", "many antioxidant", "antioxidant defence", "defence systems", "systems exist", "exist which", "which protect", "protect cells", "cells from", "from subsequent", "subsequent exposure", "exposure to", "to oxidant", "oxidant stresses.", "stresses. one", "one antioxidant", "antioxidant is", "is glutathione", "a tripeptide", "tripeptide present", "present in", "in virtually", "virtually all", "all cells", "cells that", "that regulates", "regulates the", "the intracellular", "intracellular redox", 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gamma glutamyl", "via the gamma glutamyl cycle", "gamma glutamyl cycle which", "glutamyl cycle which is", "cycle which is catalysed", "which is catalysed by six", "is catalysed by six enzymes.", "catalysed by six enzymes. in", "by six enzymes. in man", "enzymes. in man hereditary", "in man hereditary deficiencies", "man hereditary deficiencies have", "hereditary deficiencies have been found", "deficiencies have been found in", "have been found in five", "been found in five of", "found in five of the", "in five of the six", "five of the six enzymes.", "of the six enzymes. gamma", "the six enzymes. gamma glutamylcysteine", "six enzymes. gamma glutamylcysteine ligase", "gamma glutamylcysteine ligase gcl", "ligase gcl catalyses", "gcl catalyses the first", "catalyses the first and rate", "the first and rate limiting", "first and rate limiting step", "and rate limiting step in", "rate limiting step in gsh", "limiting step in gsh biosynthesis.", "step in gsh biosynthesis. gcl", "in gsh 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disease", "a disease characterised by hemolytic", "disease characterised by hemolytic anemia", "by hemolytic anemia glutathione", "hemolytic anemia glutathione deficiency", "deficiency myopathy late", "myopathy late onset spinocerebellar", "onset spinocerebellar degeneration and", "spinocerebellar degeneration and peripheral", "degeneration and peripheral neuropathy", "and peripheral neuropathy ristoff", "peripheral neuropathy ristoff &", "neuropathy ristoff & larsson", "& larsson 2007 aoyama", "larsson 2007 aoyama &", "2007 aoyama & nakaki", "aoyama & nakaki 2013 ." ] }, { "record_id": "GLY_000594_1_1700", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579000", "r hsa", "hsa 5579000", "r hsa 5579000" ] }, { "record_id": "GLY_000594_1_1700", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cyp1b1", "cyp1b1 causes", "causes glaucoma", "defective cyp1b1 causes", "cyp1b1 causes 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estradiol", "hormone estradiol 17beta", "17beta est17b", "est17b which", "which is 4", "is 4 hydroxylated", "4 hydroxylated to", "hydroxylated to 4", "to 4 hydroxyestradiol", "4 hydroxyestradiol 17beta", "hydroxyestradiol 17beta 4oh", "17beta 4oh est17b", "4oh est17b .", "est17b . defects", ". defects in", "defects in cyp1b1", "in cyp1b1 can", "cyp1b1 can cause", "can cause glaucoma", "cause glaucoma disorders", "glaucoma disorders such", "disorders such as", "such as glaucoma", "as glaucoma 3", "3 primary", "congenital a", "a glc3a", "glc3a mim:231300", "glaucoma primary", "primary open angle", "angle poag", "poag mim:137760", "1 open", "angle a", "a glc1a", "glc1a mim:137750", "mim:137750 and", "137750 and", "and peters anomaly", "anomaly pan", "pan mim:604229", "mim:604229 . these", "604229 . these", ". these disorders", "these disorders cause", "disorders cause a", "cause a progressive", "a progressive optic", "progressive optic neuropathy", "optic neuropathy characterised", 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"and peters anomaly pan", "anomaly pan mim:604229", "pan mim:604229 . these", "mim:604229 . these disorders cause", "604229 . these disorders cause", ". these disorders cause a", "these disorders cause a progressive", "disorders cause a progressive optic", "cause a progressive optic neuropathy", "a progressive optic neuropathy characterised", "progressive optic neuropathy characterised by", "optic neuropathy characterised by visual", "neuropathy characterised by visual field", "characterised by visual field defects", "by visual field defects that", "visual field defects that ultimately", "field defects that ultimately lead", "defects that ultimately lead to", "that ultimately lead to irreversible", "ultimately lead to irreversible blindness", "to irreversible blindness li", "irreversible blindness li et", "blindness li et al.", "et al. 2011 sarfarazi", "al. 2011 sarfarazi et", "2011 sarfarazi et al.", "et al. 2003 vincent", "al. 2003 vincent et", "2003 vincent et al.", "vincent et al. 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"mutations can lead to autosomal", "can lead to autosomal recessive", "lead to autosomal recessive congenital", "to autosomal recessive congenital ichthyosis", "autosomal recessive congenital ichthyosis 5", "congenital ichthyosis 5 arci5", "arci5 lefevre et", "et al. 2006 lugassy", "al. 2006 lugassy et", "2006 lugassy et al.", "lugassy et al. 2008 ." ] }, { "record_id": "GLY_000594_1_1703", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579006", "r hsa", "hsa 5579006", "r hsa 5579006" ] }, { "record_id": "GLY_000594_1_1703", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gss", "gss causes", "causes gss", "gss deficiency", "defective gss causes", "gss causes gss", "causes gss deficiency", "defective gss causes gss", "gss causes gss deficiency", "defective gss causes gss deficiency", "in mammalian", "mammalian cells", "many antioxidant", "antioxidant defence", "defence systems", 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"moderate or", "or severe", "ristoff &", "& larsson", "larsson 2007", "aoyama &", "& nakaki", "nakaki 2013", "2013 .", "in mammalian cells", "cells many", "many antioxidant defence", "antioxidant defence systems", "defence systems exist", "systems exist which", "exist which protect", "which protect cells", "protect cells from", "cells from subsequent", "from subsequent exposure", "subsequent exposure to", "exposure to oxidant", "to oxidant stresses.", "oxidant stresses. one", "stresses. one antioxidant", "one antioxidant is", "antioxidant is glutathione", "glutathione gsh", "a tripeptide present", "tripeptide present in", "present in virtually", "in virtually all", "virtually all cells", "all cells that", "cells that regulates", "that regulates the", "regulates the intracellular", "the intracellular redox", "intracellular redox state", "redox state and", "state and protects", "and protects cells", "protects cells from", "cells from oxidative", "from oxidative injury.", "oxidative 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glutathione", "six enzymes. glutathione synthetase", "enzymes. glutathione synthetase deficiency", "glutathione synthetase deficiency is", "synthetase deficiency is the", "deficiency is the most", "is the most frequently", "the most frequently recognised", "most frequently recognised disorder.", "frequently recognised disorder. defects", "recognised disorder. defects in", "disorder. defects in gss", "defects in gss can", "in gss can cause", "gss can cause glutathione", "can cause glutathione synthetase", "cause glutathione synthetase deficiency", "synthetase deficiency gssd", "deficiency gssd aka", "gssd aka 5 oxoprolinase", "aka 5 oxoprolinase deficiency", "oxoprolinase deficiency mim:266130", "mim:266130 a", "266130 a", "a severe autosomal recessive", "severe autosomal recessive disorder", "autosomal recessive disorder characterised", "recessive disorder characterised by", "disorder characterised by an", "characterised by an increased", "by an increased rate", "an increased rate of", 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infections. in this condition", "in this condition decreased", "this condition decreased levels", "condition decreased levels of", "decreased levels of cellular glutathione", "levels of cellular glutathione result", "of cellular glutathione result in", "cellular glutathione result in overstimulation", "glutathione result in overstimulation of", "result in overstimulation of gamma", "in overstimulation of gamma glutamylcysteine", "overstimulation of gamma glutamylcysteine synthesis", "of gamma glutamylcysteine synthesis and", "gamma glutamylcysteine synthesis and its", "glutamylcysteine synthesis and its subsequent", "synthesis and its subsequent conversion", "and its subsequent conversion to", "its subsequent conversion to 5", "subsequent conversion to 5 oxoproline.", "conversion to 5 oxoproline. glutathione", "to 5 oxoproline. glutathione synthetase", "5 oxoproline. glutathione synthetase deficiency", "oxoproline. glutathione synthetase deficiency can", "glutathione synthetase deficiency can be", "synthetase deficiency can be classed", "deficiency can be classed as", "can be classed as mild", "classed as mild moderate", "as mild moderate or", "mild moderate or severe", "moderate or severe ristoff", "or severe ristoff &", "severe ristoff & larsson", "& larsson 2007 aoyama", "larsson 2007 aoyama &", "2007 aoyama & nakaki", "aoyama & nakaki 2013 ." ] }, { "record_id": "GLY_000594_1_1704", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579007", "r hsa", "hsa 5579007", "r hsa 5579007" ] }, { "record_id": "GLY_000594_1_1704", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective acy1", "acy1 causes", "causes encephalopathy", "defective acy1 causes", "acy1 causes encephalopathy", "defective acy1 causes encephalopathy", "aminoacylase 1", "is a", "a cytosolic", "homodimeric zinc", "zinc binding", "binding metalloenzyme", "metalloenzyme with", "with a", "a wide", "wide 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acetylcysteine", "also hydrolyse n acetylcysteine s", "hydrolyse n acetylcysteine s conjugates.", "n acetylcysteine s conjugates. defects", "acetylcysteine s conjugates. defects in", "s conjugates. defects in acy1", "conjugates. defects in acy1 can", "defects in acy1 can cause", "in acy1 can cause aminoacylase", "acy1 can cause aminoacylase 1", "can cause aminoacylase 1 deficiency", "aminoacylase 1 deficiency acy1d", "deficiency acy1d mim:609924", "acy1d mim:609924 resulting", "mim:609924 resulting in encephalopathy", "609924 resulting in encephalopathy", "resulting in encephalopathy delay", "in encephalopathy delay in", "encephalopathy delay in psychomotor", "in psychomotor development seizures", "psychomotor development seizures and", "development seizures and increased", "seizures and increased urinary excretion", "and increased urinary excretion of", "increased urinary excretion of several", "urinary excretion of several n", "excretion of several n acetylated", "of several n 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fusions with other", "radiohumeral fusions with other skeletal", "fusions with other skeletal and", "with other skeletal and craniofacial", "other skeletal and craniofacial anomalies", "and craniofacial anomalies rhfca", "anomalies rhfca mim:614416", "mim:614416 a disease", "614416 a disease", "a disease characterised by craniofacial", "disease characterised by craniofacial malformations", "characterised by craniofacial malformations and", "by craniofacial malformations and multiple", "craniofacial malformations and multiple skeletal", "malformations and multiple skeletal anomalies", "multiple skeletal anomalies laue", "skeletal anomalies laue et", "anomalies laue et al.", "laue et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1708", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579019", "r hsa", "hsa 5579019", "r hsa 5579019" ] }, { "record_id": "GLY_000594_1_1708", "filename": "human_protein_pathways_reactome", "fieldtype": 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"human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc35d1", "slc35d1 causes", "causes schbckd", "defective slc35d1 causes", "slc35d1 causes schbckd", "defective slc35d1 causes schbckd", "the udp", "udp glucuronic", "glucuronic acid/udp", "acid/udp n", "n acetylgalactosamine", "acetylgalactosamine transporter", "is an", "an er", "er membrane", "membrane spanning", "spanning protein", "protein that", "that transports", "transports nucleotide", "nucleotide sugars", "sugars from", "from the", "the cytosol", "cytosol into", "into the", "the er", "er lumen.", "lumen. slc35d1", "slc35d1 transports", "transports udp", "udp glcua", "glcua and", "and udp", "udp galnac", "which are", "are substrates", "substrates for", "for the", "the synthesis", "synthesis of", "of chondroitin", "chondroitin sulfate", "sulfate disaccharide", "disaccharide repeats", "suggesting a", "a role", "role in", "in chondroitin", "sulfate biosynthesis.", "biosynthesis. mutations", "mutations in", "in slc35d1", "slc35d1 can", "can cause", "cause schneckenbecken", "schneckenbecken dysplasia", "a rare", "autosomal recessive", "lethal short", "short limbed", "limbed skeletal", "skeletal dysplasia", "dysplasia affecting", "affecting cartilage", "cartilage and", "and skeletal", "skeletal development", "liu et", "et al.", "al. 2010", "liu &", "& hirschberg", "hirschberg 2013", "2013 .", "the udp glucuronic", "udp glucuronic acid/udp", "glucuronic acid/udp n", "acid/udp n acetylgalactosamine", "n acetylgalactosamine transporter", "transporter slc35d1", "slc35d1 is", "is an er", "an er membrane", "er membrane spanning", "membrane spanning protein", "spanning protein that", "protein that transports", "that transports nucleotide", "transports nucleotide sugars", "nucleotide sugars from", "sugars from the", "from the cytosol", "the cytosol into", "cytosol into the", "into the er", "the er lumen.", "er lumen. slc35d1", "lumen. slc35d1 transports", "slc35d1 transports udp", "transports udp glcua", "udp glcua and", "glcua and udp", "and udp galnac", "galnac which", "which are substrates", "are substrates for", "substrates for the", "for the synthesis", "the synthesis of", "synthesis of chondroitin", "of chondroitin sulfate", "chondroitin sulfate disaccharide", "sulfate disaccharide repeats", "repeats suggesting", "suggesting a role", "a role in", "role in chondroitin", "in chondroitin sulfate", "chondroitin sulfate biosynthesis.", "sulfate biosynthesis. mutations", "biosynthesis. mutations in", "mutations in slc35d1", "in slc35d1 can", "slc35d1 can cause", "can cause schneckenbecken", "cause schneckenbecken dysplasia", "dysplasia schbckd", "schbckd mim:269250", "rare autosomal", "recessive lethal", "lethal short limbed", "short limbed skeletal", "limbed skeletal dysplasia", "skeletal dysplasia affecting", "dysplasia affecting cartilage", "affecting cartilage and", "cartilage and skeletal", "and skeletal development", "development liu", "liu et al.", "et al. 2010", "2010 liu", "liu & hirschberg", "& hirschberg 2013", "hirschberg 2013 .", "the udp glucuronic acid/udp", "udp glucuronic acid/udp n", "glucuronic acid/udp n acetylgalactosamine", "acid/udp n acetylgalactosamine transporter", "acetylgalactosamine transporter slc35d1", "slc35d1 is an", "is an er membrane", "an er membrane spanning", "er membrane spanning protein", "membrane spanning protein that", "spanning protein that transports", "protein that transports nucleotide", "that transports nucleotide sugars", "transports nucleotide sugars from", "nucleotide sugars from the", "sugars from the cytosol", "from the cytosol into", "the cytosol into the", "cytosol into the er", "into the er lumen.", "the er lumen. slc35d1", "er lumen. slc35d1 transports", "lumen. slc35d1 transports udp", "slc35d1 transports udp glcua", "transports udp glcua and", "udp glcua and udp", "glcua and udp galnac", "udp galnac which", "galnac which are", "which are substrates for", "are substrates for the", "substrates for the synthesis", "for the synthesis of", "the synthesis of chondroitin", "synthesis of chondroitin sulfate", "of chondroitin sulfate disaccharide", "chondroitin sulfate disaccharide repeats", "disaccharide repeats suggesting", "repeats suggesting a", "suggesting a role in", "a role in chondroitin", "role in chondroitin sulfate", "in chondroitin sulfate biosynthesis.", "chondroitin sulfate biosynthesis. mutations", "sulfate biosynthesis. mutations in", "biosynthesis. mutations in slc35d1", "mutations in slc35d1 can", "in slc35d1 can cause", "slc35d1 can cause schneckenbecken", "can cause schneckenbecken dysplasia", "schneckenbecken dysplasia schbckd", "mim:269250 a", "269250 a", "a rare autosomal", "rare autosomal recessive", "autosomal recessive lethal", "recessive lethal short", "lethal short limbed skeletal", "short limbed skeletal dysplasia", "limbed skeletal dysplasia affecting", "skeletal dysplasia affecting cartilage", "dysplasia affecting cartilage and", "affecting cartilage and skeletal", "cartilage and skeletal development", "skeletal development liu", "development liu et", "liu et al. 2010", "al. 2010 liu", "2010 liu &", "liu & hirschberg 2013", "& hirschberg 2013 .", "the udp glucuronic acid/udp n", "udp glucuronic acid/udp n acetylgalactosamine", "glucuronic acid/udp n acetylgalactosamine transporter", "n acetylgalactosamine transporter slc35d1", "transporter slc35d1 is", "slc35d1 is an er", "is an er membrane spanning", "an er membrane spanning protein", "er membrane spanning protein that", "membrane spanning protein that transports", "spanning protein that transports nucleotide", "protein that transports nucleotide sugars", "that transports nucleotide sugars from", "transports nucleotide sugars from the", "nucleotide sugars from the cytosol", "sugars from the cytosol into", "from the cytosol into the", "the cytosol into the er", "cytosol into the er lumen.", "into the er lumen. slc35d1", "the er lumen. slc35d1 transports", "er lumen. slc35d1 transports udp", "lumen. slc35d1 transports udp glcua", "slc35d1 transports udp glcua and", "transports udp glcua and udp", "udp glcua and udp galnac", "and udp galnac which", "udp galnac which are", "galnac which are substrates", "which are substrates for the", "are substrates for the synthesis", "substrates for the synthesis of", "for the synthesis of chondroitin", "the synthesis of chondroitin sulfate", "synthesis of chondroitin sulfate disaccharide", "of chondroitin sulfate disaccharide repeats", "sulfate disaccharide repeats suggesting", "disaccharide repeats suggesting a", "repeats suggesting a role", "suggesting a role in chondroitin", "a role in chondroitin sulfate", "role in chondroitin sulfate biosynthesis.", "in chondroitin sulfate biosynthesis. mutations", "chondroitin sulfate biosynthesis. mutations in", "sulfate biosynthesis. mutations in slc35d1", "biosynthesis. mutations in slc35d1 can", "mutations in slc35d1 can cause", "in slc35d1 can cause schneckenbecken", "slc35d1 can cause schneckenbecken dysplasia", "cause schneckenbecken dysplasia schbckd", "dysplasia schbckd mim:269250", "mim:269250 a rare", "269250 a rare", "a rare autosomal recessive", "autosomal recessive lethal short", "recessive lethal short limbed", "lethal short limbed skeletal dysplasia", "short limbed skeletal dysplasia affecting", "limbed skeletal dysplasia affecting cartilage", "skeletal dysplasia affecting cartilage and", "dysplasia affecting cartilage and skeletal", "affecting cartilage and skeletal development", "and skeletal development liu", "skeletal development liu et", "development liu et al.", "et al. 2010 liu", "al. 2010 liu &", "2010 liu & hirschberg", "liu & hirschberg 2013 ." ] }, { "record_id": "GLY_000594_1_1710", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579024", "r hsa", "hsa 5579024", "r hsa 5579024" ] }, { "record_id": "GLY_000594_1_1710", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective mat1a", "mat1a causes", "causes matd", "defective mat1a causes", "mat1a causes matd", "defective mat1a causes matd", "s adenosylmethionine", "is an", "an important", "important methyl", "methyl donor", "donor in", "in most", "most transmethylation", "transmethylation reactions.", "reactions. s", "adenosylmethionine synthase", "synthase isoform", "isoform type", "type 1", "catalyses the", "the formation", "formation of", "of adomet", "adomet from", "from methionine", "methionine and", "and atp.", "atp. defects", "defects in", "in mat1a", "mat1a can", "can cause", "cause methionine", "methionine adenosyltransferase", "adenosyltransferase deficiency", "an inborn", "inborn error", "error of", "of metabolism", "metabolism resulting", "resulting in", "in hypermethioninemia.", "hypermethioninemia. in", "in this", "this condition", "methionine accumulates", "accumulates because", "because its", "its conversion", "conversion to", "to adomet", "adomet is", "is impaired", "furujo et", "et al.", "al. 2012", "mudd 2011", "2011 .", "adenosylmethionine adomet", "adomet sam", "sam is", "is an important", "an important methyl", "important methyl donor", "methyl donor in", "donor in most", "in most transmethylation", "most transmethylation reactions.", "transmethylation reactions. s", "reactions. s adenosylmethionine", "s adenosylmethionine synthase", "adenosylmethionine synthase isoform", "synthase isoform type", "isoform type 1", "1 mat1a", "mat1a catalyses", "catalyses the formation", "the formation of", "formation of adomet", "of adomet from", "adomet from methionine", "from methionine and", "methionine and atp.", "and atp. defects", "atp. defects in", "defects in mat1a", "in mat1a can", "mat1a can cause", "can cause methionine", "cause methionine adenosyltransferase", "methionine adenosyltransferase deficiency", "deficiency matd", "matd mim:250850", "an inborn error", "inborn error of", "error of metabolism", "of metabolism resulting", "metabolism resulting in", "resulting in hypermethioninemia.", "in hypermethioninemia. in", "hypermethioninemia. in this", "in this condition", "condition methionine", "methionine accumulates because", "accumulates because its", "because its conversion", "its conversion to", "conversion to adomet", "to adomet is", "adomet is impaired", "impaired furujo", "furujo et al.", "et al. 2012", "2012 mudd", "mudd 2011 .", "s adenosylmethionine adomet", "sam is an", "is an important methyl", "an important methyl donor", "important methyl donor in", "methyl donor in most", "donor in most transmethylation", "in most transmethylation reactions.", "most transmethylation reactions. s", "transmethylation reactions. s adenosylmethionine", "reactions. s adenosylmethionine synthase", "s adenosylmethionine synthase isoform", "adenosylmethionine synthase isoform type", "synthase isoform type 1", "type 1 mat1a", "mat1a catalyses the", "catalyses the formation of", "the formation of adomet", "formation of adomet from", "of adomet from methionine", "adomet from methionine and", "from methionine and atp.", "methionine and atp. defects", "and atp. defects in", "atp. defects in mat1a", "defects in mat1a can", "in mat1a can cause", "mat1a can cause methionine", "can cause methionine adenosyltransferase", "cause methionine adenosyltransferase deficiency", "adenosyltransferase deficiency matd", "mim:250850 an", "250850 an", "an inborn error of", "inborn error of metabolism", "error of metabolism resulting", "of metabolism resulting in", "metabolism resulting in hypermethioninemia.", "resulting in hypermethioninemia. in", "in hypermethioninemia. in this", "hypermethioninemia. in this condition", "this condition methionine", "condition methionine accumulates", "methionine accumulates because its", "accumulates because its conversion", "because its conversion to", "its conversion to adomet", "conversion to adomet is", "to adomet is impaired", "is impaired furujo", "impaired furujo et", "furujo et al. 2012", "al. 2012 mudd", "2012 mudd 2011", "adenosylmethionine adomet sam", "adomet sam is", "sam is an important", "is an important methyl donor", "an important methyl donor in", "important methyl donor in most", "methyl donor in most transmethylation", "donor in most transmethylation reactions.", "in most transmethylation reactions. s", "most transmethylation reactions. s adenosylmethionine", "transmethylation reactions. s adenosylmethionine synthase", "reactions. s adenosylmethionine synthase isoform", "s adenosylmethionine synthase isoform type", "adenosylmethionine synthase isoform type 1", "isoform type 1 mat1a", "1 mat1a catalyses", "mat1a catalyses the formation", "catalyses the formation of adomet", "the formation of adomet from", "formation of adomet from methionine", "of adomet from methionine and", "adomet from methionine and atp.", "from methionine and atp. defects", "methionine and atp. defects in", "and atp. defects in mat1a", "atp. defects in mat1a can", "defects in mat1a can cause", "in mat1a can cause methionine", "mat1a can cause methionine adenosyltransferase", "can cause methionine adenosyltransferase deficiency", "methionine adenosyltransferase deficiency matd", "deficiency matd mim:250850", "mim:250850 an inborn", "250850 an inborn", "an inborn error of metabolism", "inborn error of metabolism resulting", "error of metabolism resulting in", "of metabolism resulting in hypermethioninemia.", "metabolism resulting in hypermethioninemia. in", "resulting in hypermethioninemia. in this", "in hypermethioninemia. in this condition", "in this condition methionine", "this condition methionine accumulates", "condition methionine accumulates because", "methionine accumulates because its conversion", "accumulates because its conversion to", "because its conversion to adomet", "its conversion to adomet is", "conversion to adomet is impaired", "adomet is impaired furujo", "is impaired furujo et", "impaired furujo et al.", "et al. 2012 mudd", "al. 2012 mudd 2011", "2012 mudd 2011 ." ] }, { "record_id": "GLY_000594_1_1711", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5579027", "r hsa", "hsa 5579027", "r hsa 5579027" ] }, { "record_id": "GLY_000594_1_1711", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective cyp27b1", "cyp27b1 causes", "causes vddr1b", "defective cyp27b1 causes", "cyp27b1 causes vddr1b", "defective cyp27b1 causes vddr1b", "vitamin d3", "synthesised in", "in human", "human skin", "skin by", "by ultraviolet", "ultraviolet radiation", "radiation action", "action on", "on 7", "7 dehydrocholesterol", "does not", "not possess", "possess any", "any biological", "biological activity.", "activity. vitamin", "vitamin d", "d hormonal", "hormonal activity", "activity requires", "requires hydroxylation", "hydroxylation at", "at the", "the 25", "25 and", "and 1", "1 alpha", "alpha positions", "positions by", "by cytochrome", "cytochrome p450", "p450 enzymes", "enzymes cyp2r1", "cyp2r1 and", "and cyp27b1", "cyp27b1 respectively.
              vitamin", "respectively.
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              defects", "proliferation.

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              vitamin", "cyp27b1 respectively.
              vitamin d", "respectively.
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              defects", "and proliferation.

              defects in", "proliferation.

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              vitamin", "and cyp27b1 respectively.
              vitamin d", "cyp27b1 respectively.
              vitamin d 25", "respectively.
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              defects", "differentiation and proliferation.

              defects in", "and proliferation.

              defects in cyp2r1", "proliferation.

              defects in cyp2r1 can", "in cyp2r1 can cause", "cyp2r1 can cause rickets", "cause rickets vitamin", "rickets vitamin d", "vitamin d dependent 1b", "dependent 1b vddr1b", "mim:600081 a", "600081 a", "a disorder caused by", "disorder caused by a", "caused by a selective", "by a selective deficiency", "a selective deficiency of", "selective deficiency of the", "deficiency of the active", "of the active form", "the active form of", "active form of vitamin", "form of vitamin d", "vitamin d ctl", "ctl resulting in", "resulting in defective bone", "in defective bone mineralization", "defective bone mineralization and", "bone mineralization and clinical", "mineralization and clinical features", "and clinical features of", "clinical features of rickets", "of rickets pikuleva", "rickets pikuleva et", "pikuleva et al. 2013", "et al. 2013 .", "cholecalciferol synthesised in", "synthesised in human skin by", "in human skin by ultraviolet", "human skin by ultraviolet radiation", "skin by ultraviolet radiation action", "by ultraviolet radiation action on", "ultraviolet radiation action on 7", "radiation action on 7 dehydrocholesterol", "on 7 dehydrocholesterol does", "7 dehydrocholesterol does not", "dehydrocholesterol does not possess", "does not possess any biological", "not possess any biological activity.", "possess any biological activity. vitamin", "any biological activity. vitamin d", "biological activity. vitamin d hormonal", "activity. vitamin d hormonal activity", "vitamin d hormonal activity requires", "d hormonal activity requires hydroxylation", "hormonal activity requires hydroxylation at", "activity requires hydroxylation at the", "requires hydroxylation at the 25", "hydroxylation at the 25 and", "at the 25 and 1", "the 25 and 1 alpha", "25 and 1 alpha positions", "and 1 alpha positions by", "1 alpha positions by cytochrome", "alpha positions by cytochrome p450", "positions by cytochrome p450 enzymes", "by cytochrome p450 enzymes cyp2r1", "cytochrome p450 enzymes cyp2r1 and", "p450 enzymes cyp2r1 and cyp27b1", "enzymes cyp2r1 and cyp27b1 respectively.
              vitamin", "cyp2r1 and cyp27b1 respectively.
              vitamin d", "and cyp27b1 respectively.
              vitamin d 25", "cyp27b1 respectively.
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              defects in", "differentiation and proliferation.

              defects in cyp2r1", "and proliferation.

              defects in cyp2r1 can", "proliferation.

              defects in cyp2r1 can cause", "in cyp2r1 can cause rickets", "can cause rickets vitamin", "cause rickets vitamin d", "rickets vitamin d dependent", "d dependent 1b vddr1b", "1b vddr1b mim:600081", "mim:600081 a disorder", "600081 a disorder", "a disorder caused by a", "disorder caused by a selective", "caused by a selective deficiency", "by a selective deficiency of", "a selective deficiency of the", "selective deficiency of the active", "deficiency of the active form", "of the active form of", "the active form of vitamin", "active form of vitamin d", "of vitamin d ctl", "d ctl resulting", "ctl resulting in defective", "resulting in defective bone mineralization", "in defective bone mineralization and", "defective bone mineralization and clinical", "bone mineralization and clinical features", "mineralization and clinical features of", "and clinical features of rickets", "features of rickets pikuleva", "of rickets pikuleva et", "rickets pikuleva et al.", "pikuleva et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1712", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5609974", "r hsa", "hsa 5609974", "r hsa 5609974" ] }, { "record_id": "GLY_000594_1_1712", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pgm1", "pgm1 causes", "causes pgm1", "pgm1 cdg", "defective pgm1 causes", "pgm1 causes pgm1", "causes pgm1 cdg", "defective pgm1 causes pgm1", "pgm1 causes pgm1 cdg", "defective pgm1 causes pgm1 cdg", "phosphoglucomutases 1", "1 and", "and 2", "are involved", "involved in", "in the", "the cytosolic", "cytosolic biosynthesis", "biosynthesis of", "of nucleotide", "nucleotide sugars", "sugars needed", "needed for", "for glycan", "glycan biosynthesis", "the isomerisation", "isomerisation of", "of glucose", "glucose 6", "6 phosphate", "into glucose", "glucose 1", "1 phosphate", "g1p .", ". defects", "defects in", "in pgm1", "pgm1 can", "can cause", "cause congenital", "congenital disorder", "disorder of", "of glycosylation", "glycosylation 1t", "now known", "known as", "as pgm1", "a broad", "broad spectrum", "spectrum disorder", "disorder characterised", "characterised by", "by under", "under glycosylated", "glycosylated serum", "serum glycoproteins", "timal et", "et al.", "al. 2012", "tegtmeyer et", "al. 2014", "2014 .", ". cdgs", "cdgs result", "result in", "in a", "a wide", "wide variety", "variety of", "of clinical", "clinical features", "features such", "such as", "as defects", "in nervous", "nervous system", "system development", "psychomotor retardation", "dysmorphic features", "coagulation disorders", "and immunodeficiency.", "phosphoglucomutases 1 and", "1 and 2", "2 pgm1", "pgm1 2", "2 are", "are involved in", "involved in the", "in the cytosolic", "the cytosolic biosynthesis", "cytosolic biosynthesis of", "biosynthesis of nucleotide", "of nucleotide sugars", "nucleotide sugars needed", "sugars needed for", "needed for 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"g1p . defects in", ". defects in pgm1", "defects in pgm1 can", "in pgm1 can cause", "pgm1 can cause congenital", "can cause congenital disorder", "cause congenital disorder of", "congenital disorder of glycosylation", "disorder of glycosylation 1t", "glycosylation 1t cdg1t", "cdg1t now known", "now known as pgm1", "known as pgm1 cdg", "pgm1 cdg mim:614921", "mim:614921 a", "614921 a", "a broad spectrum disorder", "broad spectrum disorder characterised", "spectrum disorder characterised by", "disorder characterised by under", "characterised by under glycosylated", "by under glycosylated serum", "under glycosylated serum glycoproteins", "serum glycoproteins timal", "glycoproteins timal et", "timal et al. 2012", "al. 2012 tegtmeyer", "2012 tegtmeyer et", "tegtmeyer et al. 2014", "et al. 2014 .", "al. 2014 . cdgs", "2014 . cdgs result", ". cdgs result in", "cdgs result in a", "result in a wide", "in a wide variety", "a wide variety of", "wide variety of clinical", "variety of clinical 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isomerisation of", "the isomerisation of glucose 6", "isomerisation of glucose 6 phosphate", "glucose 6 phosphate g6p", "phosphate g6p into", "g6p into glucose 1", "glucose 1 phosphate g1p", "1 phosphate g1p .", "phosphate g1p . defects", "g1p . defects in pgm1", ". defects in pgm1 can", "defects in pgm1 can cause", "in pgm1 can cause congenital", "pgm1 can cause congenital disorder", "can cause congenital disorder of", "cause congenital disorder of glycosylation", "congenital disorder of glycosylation 1t", "of glycosylation 1t cdg1t", "1t cdg1t now", "cdg1t now known as", "now known as pgm1 cdg", "as pgm1 cdg mim:614921", "mim:614921 a broad", "614921 a broad", "a broad spectrum disorder characterised", "broad spectrum disorder characterised by", "spectrum disorder characterised by under", "disorder characterised by under glycosylated", "characterised by under glycosylated serum", "by under glycosylated serum glycoproteins", "glycosylated serum glycoproteins timal", "serum glycoproteins timal et", "glycoproteins timal et al.", "et al. 2012 tegtmeyer", "al. 2012 tegtmeyer et", "2012 tegtmeyer et al.", "tegtmeyer et al. 2014 .", "et al. 2014 . cdgs", "al. 2014 . cdgs result", "2014 . cdgs result in", ". cdgs result in a", "cdgs result in a wide", "result in a wide variety", "in a wide variety of", "a wide variety of clinical", "wide variety of clinical features", "variety of clinical features such", "of clinical features such as", "clinical features such as defects", "features such as defects in", "such as defects in nervous", "as defects in nervous system", "defects in nervous system development", "nervous system development psychomotor", "system development psychomotor retardation", "psychomotor retardation dysmorphic features", "features hypotonia coagulation", "coagulation disorders and immunodeficiency." ] }, { "record_id": "GLY_000594_1_1713", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5609976", "r hsa", "hsa 5609976", "r hsa 5609976" ] }, { "record_id": "GLY_000594_1_1713", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective galk1", "galk1 causes", "causes galct2", "defective galk1 causes", "galk1 causes galct2", "defective galk1 causes galct2", "cytosolic galactokinase", "catalyses the", "the first", "first committed", "committed step", "step in", "in the", "the leloir", "leloir pathway", "pathway of", "of galactose", "galactose metabolism.", "metabolism. galk1", "galk1 catalyses", "the phosphorylation", "phosphorylation of", "of d", "d galactose", "to form", "form d", "galactose 1", "1 phosphate", "gal1p .", ". defects", "defects in", "in galk1", "galk1 can", "can cause", "cause type", "type ii", "ii galactosemia", "an autosomal", "autosomal recessive", "recessive deficiency", "deficiency characterised", "characterised by", "by congenital", "congenital cataracts", "cataracts during", "during infancy", "infancy and", "and 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and presenile cataracts", "and presenile cataracts in", "presenile cataracts in the", "cataracts in the adult", "in the adult population.", "the adult population. galactitol", "adult population. galactitol accumulation", "population. galactitol accumulation in", "galactitol accumulation in the", "accumulation in the lens", "in the lens is", "the lens is the", "lens is the cause", "is the cause of", "the cause of these", "cause of these cataracts", "these cataracts bosch", "cataracts bosch et", "bosch et al. 2002", "et al. 2002 .", "galactokinase galk1 catalyses", "galk1 catalyses the first", "catalyses the first committed step", "the first committed step in", "first committed step in the", "committed step in the leloir", "step in the leloir pathway", "in the leloir pathway of", "the leloir pathway of galactose", "leloir pathway of galactose metabolism.", "pathway of galactose metabolism. galk1", "of galactose metabolism. galk1 catalyses", "galactose metabolism. galk1 catalyses the", "metabolism. galk1 catalyses the phosphorylation", "galk1 catalyses the phosphorylation of", "catalyses the phosphorylation of d", "the phosphorylation of d galactose", "of d galactose gal", "galactose gal to", "gal to form d", "to form d galactose 1", "form d galactose 1 phosphate", "galactose 1 phosphate gal1p", "1 phosphate gal1p .", "phosphate gal1p . defects", "gal1p . defects in galk1", ". defects in galk1 can", "defects in galk1 can cause", "in galk1 can cause type", "galk1 can cause type ii", "can cause type ii galactosemia", "type ii galactosemia galct2", "galactosemia galct2 mim:230200", "mim:230200 an autosomal", "230200 an autosomal", "an autosomal recessive deficiency characterised", "autosomal recessive deficiency characterised by", "recessive deficiency characterised by congenital", "deficiency characterised by congenital cataracts", "characterised by congenital cataracts during", "by congenital cataracts during infancy", "congenital cataracts during infancy and", "cataracts during infancy and presenile", "during infancy and presenile cataracts", "infancy and presenile cataracts in", "and presenile cataracts in the", "presenile cataracts in the adult", "cataracts in the adult population.", "in the adult population. galactitol", "the adult population. galactitol accumulation", "adult population. galactitol accumulation in", "population. galactitol accumulation in the", "galactitol accumulation in the lens", "accumulation in the lens is", "in the lens is the", "the lens is the cause", "lens is the cause of", "is the cause of these", "the cause of these cataracts", "of these cataracts bosch", "these cataracts bosch et", "cataracts bosch et al.", "bosch et al. 2002 ." ] }, { "record_id": "GLY_000594_1_1714", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5609977", "r hsa", "hsa 5609977", "r hsa 5609977" ] }, { "record_id": "GLY_000594_1_1714", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gale", "gale causes", "causes edg", "defective gale causes", "gale causes edg", "defective gale causes edg", "cytosolic udp", "udp galactose", "galactose 4'", "4' epimerase", "catalyses the", "the reversible", "reversible interconversion", "interconversion of", "of udp", "udp d", "d galactose", "udp gal", "and udp", "udp glucose", "udp glc", "the third", "third reacton", "reacton in", "in the", "the leloir", "leloir pathway", "pathway of", "of galactose", "galactose metabolism.", "metabolism. gale", "gale can", "can also", "also catalyse", "catalyse the", "the epimerisation", "epimerisation of", "udp n", "n acetylglucosamine", "acetylglucosamine to", "to udp", "n acetylgalactosamine.", "acetylgalactosamine. the", "the active", "active form", "form of", "of the", "the enzyme", "enzyme is", "is a", "a homodimer", "homodimer with", "with one", "one molecule", "molecule of", "of bound", "bound nad", "nad per", "per monomer", "gale:nad+ 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"and mental retardation.", "mental retardation. historically", "historically it", "it was considered", "was considered that", "considered that there", "that there were", "there were two", "were two forms", "two forms of", "forms of gale", "of gale deficidency", "deficidency a", "benign \\peripheral\\", "\\peripheral\\ form", "form where there", "where there is", "there is no", "is no gale", "no gale activity", "gale activity in", "activity in red", "in red blood", "red blood cells", "blood cells and", "cells and characterised", "and characterised by", "characterised by mild", "by mild symptoms", "symptoms gitzelmann", "1972 and", "and a rarer", "a rarer \\generalised\\", "rarer \\generalised\\ form", "\\generalised\\ form with", "form with no", "with no detectable", "no detectable gale", "detectable gale activity", "activity in all", "in all tissues", "all tissues resulting", "tissues resulting in", "resulting in more", "in more severe", "more severe symptoms", "symptoms holton", "holton et al.", "et al. 1981", "al. 1981 .", "1981 . the", ". the disease", "the disease is", "disease is now", "is now considered", "now considered to", "considered to be", "to be a", "be a continuum", "continuum openo", "openo et al.", "et al. 2006", "al. 2006 .", "cytosolic udp galactose 4'", "udp galactose 4' epimerase", "4' epimerase gale", "gale catalyses the", "catalyses the reversible interconversion", "the reversible interconversion of", "reversible interconversion of udp", "interconversion of udp d", "of udp d galactose", "d galactose udp", "galactose udp gal", "udp gal and", "gal and udp", "udp glucose udp", "glucose udp glc", "glc the", "the third reacton in", "third reacton in the", "reacton in the leloir", "in the leloir pathway", "the leloir pathway of", "leloir pathway of galactose", "pathway of galactose metabolism.", "of galactose metabolism. gale", "galactose metabolism. gale can", "metabolism. gale can also", "gale can also catalyse", "can also catalyse the", "also 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galactosemia edg", "mim:230350 or", "230350 or", "or type iii galactosemia", "iii galactosemia diseases", "galactosemia diseases of", "diseases of galactose metabolism", "galactose metabolism whose", "metabolism whose clinical", "whose clinical features include", "clinical features include early", "features include early onset", "include early onset cataracts", "onset cataracts liver", "cataracts liver damage", "liver damage deafness", "damage deafness and", "deafness and mental retardation.", "and mental retardation. historically", "retardation. historically it", "historically it was", "it was considered that", "was considered that there", "considered that there were", "that there were two", "there were two forms", "were two forms of", "two forms of gale", "forms of gale deficidency", "gale deficidency a", "deficidency a benign", "a benign \\peripheral\\", "\\peripheral\\ form where", "form where there is", "where there is no", "there is no gale", "is no gale activity", "no gale 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activity in all", "gale activity in all tissues", "activity in all tissues resulting", "in all tissues resulting in", "all tissues resulting in more", "tissues resulting in more severe", "resulting in more severe symptoms", "more severe symptoms holton", "severe symptoms holton et", "symptoms holton et al.", "holton et al. 1981 .", "et al. 1981 . the", "al. 1981 . the disease", "1981 . the disease is", ". the disease is now", "the disease is now considered", "disease is now considered to", "is now considered to be", "now considered to be a", "considered to be a continuum", "be a continuum openo", "a continuum openo et", "continuum openo et al.", "openo et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1715", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "561048", "r hsa", "hsa 561048", "r hsa 561048" ] }, { "record_id": "GLY_000594_1_1715", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ 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"human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc17a5", "slc17a5 causes", "causes salla", "salla disease", "and issd", "defective slc17a5 causes", "slc17a5 causes salla", "causes salla disease", "disease sd", "sd and", "defective slc17a5 causes salla", "slc17a5 causes salla disease", "salla disease sd", "sd and issd", "defective slc17a5 causes salla disease", "causes salla disease sd", "disease sd and", "slc17a5 encodes", "encodes a", "a lysosomal", "lysosomal sialic", "sialic acid", "acid transporter", "membrane glycoprotein", "glycoprotein hp59", "which exports", "exports sialic", "n acetylneuraminic", "acetylneuraminic acid", "derived from", "from the", "the degradation", "degradation of", "of glycoconjugates", "glycoconjugates from", "from lysosomes.", "lysosomes. this", "this export", "export is", "is dependent", "dependent on", "on the", "the proton", "proton electrochemical", "electrochemical gradient", "gradient across", "across the", "the 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"neu5ac derived", "derived from the", "from the degradation", "the degradation of", "degradation of glycoconjugates", "of glycoconjugates from", "glycoconjugates from lysosomes.", "from lysosomes. this", "lysosomes. this export", "this export is", "export is dependent", "is dependent on", "dependent on the", "on the proton", "the proton electrochemical", "proton electrochemical gradient", "electrochemical gradient across", "gradient across the", "across the lysosomal", "the lysosomal membrane.", "lysosomal membrane. slc17a5", "membrane. slc17a5 is", "slc17a5 is present", "is present in", "present in the", "in the pathological", "the pathological tumor", "pathological tumor vasculature", "tumor vasculature of", "vasculature of the", "of the lung", "lung breast", "breast colon", "colon and", "ovary but", "but not in", "not in the", "in the normal", "the normal vasculature", "vasculature suggesting", "suggesting that the", "that the protein", "the protein may", "protein may be", "may be 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"and are autosomal", "are autosomal recessive", "autosomal recessive neurodegenerative", "recessive neurodegenerative disorders", "neurodegenerative disorders characterised", "disorders characterised by", "characterised by hypotonia", "hypotonia cerebellar", "cerebellar ataxia and", "ataxia and mental", "and mental retardation", "mental retardation with", "retardation with patients", "with patients excreting", "patients excreting large", "excreting large amounts", "large amounts of", "amounts of free", "of free neu5ac", "free neu5ac in", "neu5ac in urine.", "in urine. issd", "urine. issd is", "issd is a", "is a severe", "a severe infantile", "severe infantile form", "infantile form of", "form of sasd", "of sasd with", "sasd with a", "with a more", "a more severe", "more severe clinical", "severe clinical course", "clinical course than", "course than sd", "sd verheijen", "verheijen et al.", "et al. 1999", "1999 aula", "aula et al.", "et al. 2000", "al. 2000 .", "slc17a5 encodes a 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is significantly expressed", "is significantly expressed in", "significantly expressed in human", "expressed in human fetal", "in human fetal lung.", "human fetal lung. defects", "fetal lung. defects in", "lung. defects in slc17a5", "defects in slc17a5 cause", "in slc17a5 cause salla", "slc17a5 cause salla disease", "sd and infantile", "and infantile sialic acid", "infantile sialic acid storage", "sialic acid storage disorder", "storage disorder issd", "disorder issd aka", "issd aka n acetylneuraminic", "aka n acetylneuraminic acid", "n acetylneuraminic acid storage", "acetylneuraminic acid storage disease", "storage disease nsd", "disease nsd .", "nsd . these diseases", ". these diseases belong", "these diseases belong to", "diseases belong to the", "belong to the sialic", "to the sialic acid", "the sialic acid storage", "sialic acid storage diseases", "storage diseases sasds", "sasds and", "and are autosomal recessive", "are autosomal recessive neurodegenerative", "autosomal 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suggesting that the", "suggesting that the protein may", "that the protein may be", "the protein may be critical", "protein may be critical to", "may be critical to pathological", "be critical to pathological angiogenesis.", "critical to pathological angiogenesis. sialin", "to pathological angiogenesis. sialin is", "pathological angiogenesis. sialin is not", "angiogenesis. sialin is not expressed", "sialin is not expressed in", "is not expressed in a", "not expressed in a variety", "expressed in a variety of", "in a variety of normal", "a variety of normal tissues", "of normal tissues but", "normal tissues but is", "tissues but is significantly", "but is significantly expressed in", "is significantly expressed in human", "significantly expressed in human fetal", "expressed in human fetal lung.", "in human fetal lung. defects", "human fetal lung. defects in", "fetal lung. defects in slc17a5", "lung. defects in slc17a5 cause", "defects in slc17a5 cause salla", "in slc17a5 cause salla disease", "cause salla disease sd", "sd and infantile sialic", "and infantile sialic acid storage", "infantile sialic acid storage disorder", "acid storage disorder issd", "storage disorder issd aka", "disorder issd aka n", "issd aka n acetylneuraminic acid", "aka n acetylneuraminic acid storage", "n acetylneuraminic acid storage disease", "acid storage disease nsd", "storage disease nsd .", "disease nsd . these", "nsd . these diseases belong", ". these diseases belong to", "these diseases belong to the", "diseases belong to the sialic", "belong to the sialic acid", "to the sialic acid storage", "the sialic acid storage diseases", "acid storage diseases sasds", "sasds and are", "and are autosomal recessive neurodegenerative", "are autosomal recessive neurodegenerative disorders", "autosomal recessive neurodegenerative disorders characterised", "recessive neurodegenerative disorders characterised by", "neurodegenerative disorders characterised by hypotonia", "characterised by hypotonia 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"than sd verheijen et", "sd verheijen et al.", "et al. 1999 aula", "al. 1999 aula et", "1999 aula et al.", "aula et al. 2000 ." ] }, { "record_id": "GLY_000594_1_1717", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619036", "r hsa", "hsa 5619036", "r hsa 5619036" ] }, { "record_id": "GLY_000594_1_1717", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc24a5", "slc24a5 causes", "causes oculocutaneous", "oculocutaneous albinism", "albinism 6", "defective slc24a5 causes", "slc24a5 causes oculocutaneous", "causes oculocutaneous albinism", "oculocutaneous albinism 6", "6 oca6", "defective slc24a5 causes oculocutaneous", "slc24a5 causes oculocutaneous albinism", "causes oculocutaneous albinism 6", "albinism 6 oca6", "defective slc24a5 causes oculocutaneous albinism", "slc24a5 causes oculocutaneous albinism 6", "oculocutaneous albinism 6 oca6", "five members", "members of", "of the", 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patients", "patients with", "with this", "this condition", "condition show", "show accompanied", "accompanied eye", "eye symptoms", "kamaraj &", "& purohit", "purohit 2014", "morice picard", "picard et", "al. 2014", "2014 .", "five members of", "members of the", "of the nckx", "nckx slc24", "slc24 family", "family are all", "are all able", "all able to", "able to exchange", "to exchange one", "exchange one ca2+", "one ca2+ and", "ca2+ and one", "and one k+", "one k+ for", "k+ for four", "for four na+.", "four na+. slc24a5", "slc24a5 nckx5", "nckx5 located", "located on the", "on the trans", "the trans golgi", "trans golgi membrane", "membrane is", "is the prediminant", "the prediminant k+", "prediminant k+ dependent", "k+ dependent na+/ca2+", "dependent na+/ca2+ exchanger", "na+/ca2+ exchanger in", "exchanger in melanocytes", "in melanocytes and", "melanocytes and is", "and is one", "is one of", "one of a", "of a handful", "a handful of", "handful of genes", "of genes thought", "genes 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neuropathy mental", "sensorimotor neuropathy mental retardation", "mental retardation dysmorphic features", "retardation dysmorphic features and", "dysmorphic features and variable degree", "features and variable degree of", "and variable degree of agenesis", "variable degree of agenesis of", "degree of agenesis of the", "the corpus callosum howard", "corpus callosum howard et", "callosum howard et al.", "et al. 2002 dupre", "al. 2002 dupre et", "2002 dupre et al.", "et al. 2003 salin", "al. 2003 salin cantegrel", "2003 salin cantegrel et", "salin cantegrel et al. 2011", "cantegrel et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1720", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619040", "r hsa", "hsa 5619040", "r hsa 5619040" ] }, { "record_id": "GLY_000594_1_1720", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc34a1", "slc34a1 causes", "causes hypophosphatemic", "hypophosphatemic nephrolithiasis/osteoporosis", "nephrolithiasis/osteoporosis 1", "defective slc34a1 causes", "slc34a1 causes hypophosphatemic", "causes hypophosphatemic nephrolithiasis/osteoporosis", "hypophosphatemic nephrolithiasis/osteoporosis 1", "1 nphlop1", "defective slc34a1 causes hypophosphatemic", "slc34a1 causes hypophosphatemic nephrolithiasis/osteoporosis", "causes hypophosphatemic nephrolithiasis/osteoporosis 1", "nephrolithiasis/osteoporosis 1 nphlop1", "defective slc34a1 causes hypophosphatemic nephrolithiasis/osteoporosis", "slc34a1 causes hypophosphatemic nephrolithiasis/osteoporosis 1", "hypophosphatemic nephrolithiasis/osteoporosis 1 nphlop1", "slc34a1 and", "and 2", "2 encode", "encode na+/pi", "na+/pi cotransporters", "which cotransport", "cotransport divalent", "divalent phosphate", "po4 2", "with 3", "3 na+", "na+ ions.", "ions. slc34a1", "slc34a1 is", "is an", "an important", "important pi", "pi transporter", "transporter mainly", "mainly expressed", "expressed in", "in renal", "renal proximal", "proximal tubules", "tubules where", "where it", "it plays", "plays a", "a major", "major role", "role in", "in pi", "pi homeostasis.", "homeostasis. defects", "defects in", "in slc34a1", "slc34a1 are", "are the", "the cause", "cause of", "of hypophosphatemic", "nephrolithiasis/osteoporosis type", "type 1", "disease characterised", "characterised by", "by decreased", "decreased renal", "renal phosphate", "phosphate absorption", "nephrolithiasis and", "and implicated", "implicated in", "in the", "the formation", "formation of", "of renal", "renal calcium", "calcium stones", "stones and/or", "and/or bone", "bone demineralisation", "prie et", "et al.", "al. 2002", "al. 2004", "choi 2008", "boskey et", "al. 2013", "forster et", "2013 .", "slc34a1 and 2", "and 2 encode", "2 encode na+/pi", "encode na+/pi cotransporters", "cotransporters which", "which cotransport divalent", "cotransport divalent phosphate", "phosphate po4", "pi with", "with 3 na+", "3 na+ ions.", "na+ ions. slc34a1", "ions. slc34a1 is", "slc34a1 is an", "is an important", "an important pi", "important pi transporter", "pi transporter mainly", "transporter mainly expressed", "mainly expressed in", "expressed in renal", "in renal proximal", "renal proximal tubules", "proximal tubules where", "tubules where it", "where it plays", "it plays a", "plays a major", "a major role", "major role in", "role in pi", "in pi homeostasis.", "pi homeostasis. defects", "homeostasis. defects in", "defects in slc34a1", "in slc34a1 are", "slc34a1 are the", "are the cause", "the cause of", "cause of hypophosphatemic", "of hypophosphatemic nephrolithiasis/osteoporosis", "hypophosphatemic nephrolithiasis/osteoporosis type", "nephrolithiasis/osteoporosis type 1", "nphlop1 mim:612286", "disease characterised by", "characterised by decreased", "by decreased renal", "decreased renal phosphate", "renal phosphate absorption", "absorption hypophosphatemia", "hypophosphatemia hyperphosphaturia", "hyperphosphaturia hypercalciuria", "hypercalciuria nephrolithiasis", "nephrolithiasis and implicated", "and implicated in", "implicated in the", "in the formation", "the formation of", "formation of renal", "of renal calcium", "renal calcium stones", "calcium stones and/or", "stones and/or bone", "and/or bone demineralisation", "demineralisation prie", "prie et al.", "et al. 2002", "2002 prie", "et al. 2004", "2004 choi", "2008 boskey", "boskey et al.", "et al. 2013", "2013 forster", "forster et al.", "al. 2013 .", "slc34a1 and 2 encode", "and 2 encode na+/pi", "2 encode na+/pi cotransporters", "na+/pi cotransporters which", "cotransporters which cotransport", "which cotransport divalent phosphate", "divalent phosphate po4", "phosphate po4 2", "pi with 3", "with 3 na+ ions.", "3 na+ ions. slc34a1", "na+ ions. slc34a1 is", "ions. slc34a1 is an", "slc34a1 is an important", "is an important pi", "an important pi transporter", "important pi transporter mainly", "pi transporter mainly expressed", "transporter mainly expressed in", "mainly expressed in renal", "expressed in renal proximal", "in renal proximal tubules", "renal proximal tubules where", "proximal tubules where it", "tubules where it plays", "where it plays a", "it plays a major", "plays a major role", "a major role in", "major role in pi", "role in pi homeostasis.", "in pi homeostasis. defects", "pi homeostasis. defects in", "homeostasis. defects in slc34a1", "defects in slc34a1 are", "in slc34a1 are the", "slc34a1 are the cause", "are the cause of", "the cause of hypophosphatemic", "cause of hypophosphatemic nephrolithiasis/osteoporosis", "of hypophosphatemic nephrolithiasis/osteoporosis type", "hypophosphatemic nephrolithiasis/osteoporosis type 1", "type 1 nphlop1", "mim:612286 disease", "612286 disease", "disease characterised by decreased", "characterised by decreased renal", "by decreased renal phosphate", "decreased renal phosphate absorption", "phosphate absorption hypophosphatemia", "hypercalciuria nephrolithiasis and", "nephrolithiasis and implicated in", "and implicated in the", "implicated in the formation", "in the formation of", "the formation of renal", "formation of renal calcium", "of renal calcium stones", "renal calcium stones and/or", "calcium stones and/or bone", "stones and/or bone demineralisation", "bone demineralisation prie", "demineralisation prie et", "prie et al. 2002", "al. 2002 prie", "2002 prie et", "prie et al. 2004", "al. 2004 choi", "2004 choi 2008", "choi 2008 boskey", "2008 boskey et", "boskey et al. 2013", "al. 2013 forster", "2013 forster et", "forster et al. 2013", "et al. 2013 .", "slc34a1 and 2 encode na+/pi", "and 2 encode na+/pi cotransporters", "encode na+/pi cotransporters which", "na+/pi cotransporters which cotransport", "cotransporters which cotransport divalent", "cotransport divalent phosphate po4", "divalent phosphate po4 2", "2 pi", "pi with 3 na+", "with 3 na+ ions. slc34a1", "3 na+ ions. slc34a1 is", "na+ ions. slc34a1 is an", "ions. slc34a1 is an important", "slc34a1 is an important pi", "is an important pi transporter", "an important pi transporter mainly", "important pi transporter mainly expressed", "pi transporter mainly expressed in", "transporter mainly expressed in renal", "mainly expressed in renal proximal", "expressed in renal proximal tubules", "in renal proximal tubules where", "renal proximal tubules where it", "proximal tubules where it plays", "tubules where it plays a", "where it plays a major", "it plays a major role", "plays a major role in", "a major role in pi", "major role in pi homeostasis.", "role in pi homeostasis. defects", "in pi homeostasis. defects in", "pi homeostasis. defects in slc34a1", "homeostasis. defects in slc34a1 are", "defects in slc34a1 are the", "in slc34a1 are the cause", "slc34a1 are the cause of", "are the cause of hypophosphatemic", "the cause of hypophosphatemic nephrolithiasis/osteoporosis", "cause of hypophosphatemic nephrolithiasis/osteoporosis type", "of hypophosphatemic nephrolithiasis/osteoporosis type 1", "nephrolithiasis/osteoporosis type 1 nphlop1", "1 nphlop1 mim:612286", "mim:612286 disease characterised", "612286 disease characterised", "disease characterised by decreased renal", "characterised by decreased renal phosphate", "by decreased renal phosphate absorption", "renal phosphate absorption hypophosphatemia", "absorption hypophosphatemia hyperphosphaturia", "hypophosphatemia hyperphosphaturia hypercalciuria", "hyperphosphaturia hypercalciuria nephrolithiasis", "hypercalciuria nephrolithiasis and implicated", "nephrolithiasis and implicated in the", "and implicated in the formation", "implicated in the formation of", "in the formation of renal", "the formation of renal calcium", "formation of renal calcium stones", "of renal calcium stones and/or", "renal calcium stones and/or bone", "calcium stones and/or bone demineralisation", "and/or bone demineralisation prie", "bone demineralisation prie et", "demineralisation prie et al.", "et al. 2002 prie", "al. 2002 prie et", "2002 prie et al.", "et al. 2004 choi", "al. 2004 choi 2008", "choi 2008 boskey et", "2008 boskey et al.", "et al. 2013 forster", "al. 2013 forster et", "2013 forster et al.", "forster et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1721", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619041", "r hsa", "hsa 5619041", "r hsa 5619041" ] }, { "record_id": "GLY_000594_1_1721", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc36a2", "slc36a2 causes", "causes iminoglycinuria", "and hyperglycinuria", "defective slc36a2 causes", "slc36a2 causes iminoglycinuria", "iminoglycinuria ig", "ig and", "hyperglycinuria hg", "defective slc36a2 causes iminoglycinuria", "causes iminoglycinuria ig", "ig and hyperglycinuria", "and hyperglycinuria hg", "slc36a2 causes iminoglycinuria ig", "iminoglycinuria ig and", "slc36a2 encodes", "encodes proton", "proton coupled", "coupled amino", "amino acid", "acid transporter", "transporter 2", "a high", "high affinity", "affinity cotransporter", "cotransporter of", "of glycine", "glycine and", "and proline", "proline coupled", "coupled with", "with the", "the uptake", "uptake of", "of a", "a proton", "proton in", "in kidney", "kidney and", "and muscles", "schweikhard &", "& ziegler", "ziegler 2012", "2012 .", ". defects", "defects in", "in slc36a2", "slc36a2 can", "can cause", "cause iminoglycinuria", "an autosomal", "autosomal recessive", "recessive abnormality", "abnormality of", "of renal", "renal transport", "transport of", "and the", "the imino", "imino acids", "acids proline", "proline and", "and hydroxyproline.", "hydroxyproline. defects", "defects can", "can also", "also cause", "cause hyperglycinuria", "a related", "related disorder", "disorder to", "to ig", "ig which", "which is", "is characterised", "characterised by", "by excess", "excess glycine", "glycine in", "in the", "the urine", "broer et", "et al.", "al. 2008", "2008 .", ". polymorphisms", "polymorphisms in", "the modifiers", "modifiers slc6a18", "19 and", "and 20", "contribute to", "to these", "these phenotypes.", "slc36a2 encodes proton", "encodes proton coupled", "proton coupled amino", "coupled amino acid", "amino acid transporter", "acid transporter 2", "2 pat2", "a high affinity", "high affinity cotransporter", "affinity cotransporter of", "cotransporter of glycine", "of glycine and", "glycine and proline", "and proline coupled", "proline coupled with", "coupled with the", "with the uptake", "the uptake of", "uptake of a", "of a proton", "a proton in", "proton in kidney", "in kidney and", "kidney and muscles", "muscles schweikhard", "schweikhard & ziegler", "& ziegler 2012", "ziegler 2012 .", "2012 . defects", ". defects in", "defects in slc36a2", "in slc36a2 can", "slc36a2 can cause", "can cause iminoglycinuria", "ig mim:242600", "an autosomal recessive", "autosomal recessive abnormality", "recessive abnormality of", "abnormality of renal", "of renal transport", "renal transport of", "transport of glycine", "glycine and the", "and the imino", "the imino acids", "imino acids proline", "acids proline and", "proline and hydroxyproline.", "and hydroxyproline. defects", "hydroxyproline. defects can", "defects can also", "can also cause", "also cause hyperglycinuria", "hg mim:138500", "a related disorder", "related disorder to", "disorder to ig", "to ig which", "ig which is", "which is characterised", "is characterised by", "characterised by excess", "by excess glycine", "excess glycine in", "glycine in the", "in the urine", "urine broer", "broer et al.", "et al. 2008", "al. 2008 .", "2008 . polymorphisms", ". polymorphisms in", "polymorphisms in the", "in the modifiers", "the modifiers slc6a18", "slc6a18 19", "19 and 20", "20 contribute", "contribute to these", "to these phenotypes.", "slc36a2 encodes proton coupled", "encodes proton coupled amino", "proton coupled amino acid", "coupled amino acid transporter", "amino acid transporter 2", "transporter 2 pat2", "pat2 a", "a high affinity cotransporter", "high affinity cotransporter of", "affinity cotransporter of glycine", "cotransporter of glycine and", "of glycine and proline", "glycine and proline coupled", "and proline coupled with", "proline coupled with the", "coupled with the uptake", "with the uptake of", "the uptake of a", "uptake of a proton", "of a proton in", "a proton in kidney", "proton in kidney and", "in kidney and muscles", "and muscles schweikhard", "muscles schweikhard &", "schweikhard & ziegler 2012", "& ziegler 2012 .", "ziegler 2012 . defects", "2012 . defects in", ". defects in slc36a2", "defects in slc36a2 can", "in slc36a2 can cause", "slc36a2 can cause iminoglycinuria", "cause iminoglycinuria ig", "mim:242600 an", "242600 an", "an autosomal recessive abnormality", "autosomal recessive abnormality of", "recessive abnormality of renal", "abnormality of renal transport", "of renal transport of", "renal transport of glycine", "transport of glycine and", "of glycine and the", "glycine and the imino", "and the imino acids", "the imino acids proline", "imino acids proline and", "acids proline and hydroxyproline.", "proline and hydroxyproline. defects", "and hydroxyproline. defects can", "hydroxyproline. defects can also", "defects can also cause", "can also cause hyperglycinuria", "cause hyperglycinuria hg", "mim:138500 a", "138500 a", "a related disorder to", "related disorder to ig", "disorder to ig which", "to ig which is", "ig which is characterised", "which is characterised by", "is characterised by excess", "characterised by excess glycine", "by excess glycine in", "excess glycine in the", "glycine in the urine", "the urine broer", "urine broer et", "broer et al. 2008", "et al. 2008 .", "al. 2008 . polymorphisms", "2008 . polymorphisms in", ". polymorphisms in the", "polymorphisms in the modifiers", "in the modifiers slc6a18", "modifiers slc6a18 19", "slc6a18 19 and", "and 20 contribute", "20 contribute to", "contribute to these phenotypes.", "slc36a2 encodes proton coupled amino", "encodes proton coupled amino acid", "proton coupled amino acid transporter", "coupled amino acid transporter 2", "acid transporter 2 pat2", "pat2 a high", "a high affinity cotransporter of", "high affinity cotransporter of glycine", "affinity cotransporter of glycine and", "cotransporter of glycine and proline", "of glycine and proline coupled", "glycine and proline coupled with", "and proline coupled with the", "proline coupled with the uptake", "coupled with the uptake of", "with the uptake of a", "the uptake of a proton", "uptake of a proton in", "of a proton in kidney", "a proton in kidney and", "proton in kidney and muscles", "kidney and muscles schweikhard", "and muscles schweikhard &", "muscles schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . defects", "ziegler 2012 . defects in", "2012 . defects in slc36a2", ". defects in slc36a2 can", "defects in slc36a2 can cause", "in slc36a2 can cause iminoglycinuria", "can cause iminoglycinuria ig", "iminoglycinuria ig mim:242600", "mim:242600 an autosomal", "242600 an autosomal", "an autosomal recessive abnormality of", "autosomal recessive abnormality of renal", "recessive abnormality of renal transport", "abnormality of renal transport of", "of renal transport of glycine", "renal transport of glycine and", "transport of glycine and the", "of glycine and the imino", "glycine and the imino acids", "and the imino acids proline", "the imino acids proline and", "imino acids proline and hydroxyproline.", "acids proline and hydroxyproline. defects", "proline and hydroxyproline. defects can", "and hydroxyproline. defects can also", "hydroxyproline. defects can also cause", "defects can also cause hyperglycinuria", "also cause hyperglycinuria hg", "hyperglycinuria hg mim:138500", "mim:138500 a related", "138500 a related", "a related disorder to ig", "related disorder to ig which", "disorder to ig which is", "to ig which is characterised", "ig which is characterised by", "which is characterised by excess", "is characterised by excess glycine", "characterised by excess glycine in", "by excess glycine in the", "excess glycine in the urine", "in the urine broer", "the urine broer et", "urine broer et al.", "broer et al. 2008 .", "et al. 2008 . polymorphisms", "al. 2008 . polymorphisms in", "2008 . polymorphisms in the", ". polymorphisms in the modifiers", "polymorphisms in the modifiers slc6a18", "the modifiers slc6a18 19", "modifiers slc6a18 19 and", "slc6a18 19 and 20", "19 and 20 contribute", "and 20 contribute to", "20 contribute to these" ] }, { "record_id": "GLY_000594_1_1722", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619042", "r hsa", "hsa 5619042", "r hsa 5619042" ] }, { "record_id": "GLY_000594_1_1722", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective rhag", "rhag causes", "causes regulator", "regulator type", "type rh", "rh null", "null hemolytic", "hemolytic anemia", "defective rhag causes", "rhag causes regulator", "causes regulator type", "regulator type rh", "type rh null", "rh null hemolytic", "null hemolytic anemia", "anemia rhn", "defective rhag causes regulator", "rhag causes regulator type", "causes regulator type rh", "regulator type rh null", "type rh null hemolytic", "rh null hemolytic anemia", "hemolytic anemia rhn", "defective rhag causes regulator type", "rhag causes regulator type rh", "causes regulator type rh null", "regulator type rh null hemolytic", "type rh null hemolytic anemia", "null hemolytic anemia rhn", "blood group", "group antigens", "antigens consist", "consist of", "of several", "several membrane", "membrane associated", "associated polypeptides", "polypeptides including", "including rhag", "which is", "is 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erythroid", "erythroid cells.", "cells. a", "a transport", "transport function", "function for", "for rhag", "rhag is", "is suggested", "suggested to", "to mediate", "mediate ammonium", "export from", "from these", "these cells", "cells and", "and prevent", "prevent toxic", "toxic build", "build up", "up of", "of nh3/nh4+", "westhoff et", "et al.", "al. 2002", "ripoche et", "al. 2004", "2004 .", ". defects", "defects in", "in rhag", "rhag are", "are the", "the cause", "cause of", "of regulator", "rh deficiency", "deficiency syndrome", "syndrome .", ". rhn", "rhn is", "is a", "a form", "form of", "of chronic", "chronic hemolytic", "huang &", "& ye", "ye 2010", "2010 .", "rhesus rh", "rh blood", "blood group antigens", "group antigens consist", "antigens consist of", "consist of several", "of several membrane", "several membrane associated", "membrane associated polypeptides", "associated polypeptides including", "polypeptides including rhag", "rhag which", "which is required", "is 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2004", "al. 2004 .", "2004 . defects", ". defects in", "defects in rhag", "in rhag are", "rhag are the", "are the cause", "the cause of", "cause of regulator", "of regulator type", "rhn rh", "rh deficiency syndrome", "deficiency syndrome .", "syndrome . rhn", ". rhn is", "rhn is a", "is a form", "a form of", "form of chronic", "of chronic hemolytic", "chronic hemolytic anemia", "anemia huang", "huang & ye", "& ye 2010", "ye 2010 .", "rh blood group", "blood group antigens consist", "group antigens consist of", "antigens consist of several", "consist of several membrane", "of several membrane associated", "several membrane associated polypeptides", "membrane associated polypeptides including", "associated polypeptides including rhag", "including rhag which", "rhag which is", "which is required for", "is required for cell", "required for cell surface", "for cell surface expression", "cell surface expression of", "surface expression of the", "expression of the complex.", "of the complex. 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hemolytic anemia huang", "hemolytic anemia huang &", "anemia huang & ye", "huang & ye 2010 ." ] }, { "record_id": "GLY_000594_1_1723", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619044", "r hsa", "hsa 5619044", "r hsa 5619044" ] }, { "record_id": "GLY_000594_1_1723", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc6a19", "slc6a19 causes", "causes hartnup", "hartnup disorder", "defective slc6a19 causes", "slc6a19 causes hartnup", "causes hartnup disorder", "disorder hnd", "defective slc6a19 causes hartnup", "slc6a19 causes hartnup disorder", "hartnup disorder hnd", "defective slc6a19 causes hartnup disorder", "causes hartnup disorder hnd", "slc6a19 encodes", "encodes the", "the sodium", "sodium dependent", "dependent neutral", "neutral amino", "amino acid", "acid transporter", "transporter b", "b 0", "0 at1", "at1 and", "and mediates", "mediates the", "the uptake", "uptake 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rashes", "cerebellar ataxia", "ataxia and", "and psychotic", "psychotic behaviour", "broer 2009", "cheon et", "et al.", "al. 2010", "2010 .", ". some", "some mutations", "mutations in", "slc6a19 are", "are thought", "thought to", "to contribute", "contribute to", "to the", "the phenotypes", "phenotypes iminoglycinuria", "and hyperglycinuria", "broer et", "al. 2008", "2008 .", "slc6a19 encodes the", "encodes the sodium", "the sodium dependent", "sodium dependent neutral", "dependent neutral amino", "neutral amino acid", "amino acid transporter", "acid transporter b", "transporter b 0", "b 0 at1", "0 at1 and", "at1 and mediates", "and mediates the", "mediates the uptake", "the uptake of", "uptake of neutral", "of neutral amino", "neutral amino acids", "amino acids across", "acids across the", "across the plasma", "the plasma membrane", "plasma membrane accompanied", "membrane accompanied by", "accompanied by uptake", "by uptake of", "uptake of a", "of a sodium", "a sodium ion.", "sodium 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broer", "psychotic behaviour broer 2009", "broer 2009 cheon et", "2009 cheon et al.", "cheon et al. 2010 .", "et al. 2010 . some", "al. 2010 . some mutations", "2010 . some mutations in", ". some mutations in slc6a19", "some mutations in slc6a19 are", "mutations in slc6a19 are thought", "in slc6a19 are thought to", "slc6a19 are thought to contribute", "are thought to contribute to", "thought to contribute to the", "to contribute to the phenotypes", "contribute to the phenotypes iminoglycinuria", "the phenotypes iminoglycinuria ig", "iminoglycinuria ig mim:242600", "ig mim:242600 and", "hyperglycinuria hg mim:138500", "mim:138500 broer et", "138500 broer et", "broer et al. 2008 ." ] }, { "record_id": "GLY_000594_1_1724", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619047", "r hsa", "hsa 5619047", "r hsa 5619047" ] }, { "record_id": "GLY_000594_1_1724", "filename": "human_protein_pathways_reactome", "fieldtype": "text", 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proximal", "permanent isolated proximal renal", "isolated proximal renal tubular", "proximal renal tubular acidosis", "renal tubular acidosis with", "tubular acidosis with ocular", "acidosis with ocular abnormalities", "oa a", "a rare autosomal recessive", "rare autosomal recessive syndrome", "autosomal recessive syndrome characterised", "recessive syndrome characterised by", "syndrome characterised by short", "characterised by short stature", "short stature proximal", "stature proximal renal", "tubular acidosis mental", "acidosis mental retardation", "mental retardation bilateral", "retardation bilateral glaucoma", "bilateral glaucoma cataracts", "glaucoma cataracts and", "cataracts and bandkeratopathy. prta", "and bandkeratopathy. prta results", "bandkeratopathy. prta results from", "prta results from the", "results from the failure", "from the failure of", "the failure of the", "failure of the proximal", "of the proximal tubular", "the proximal tubular cells", "proximal tubular cells to", "tubular cells to reabsorb", "cells to reabsorb filtered", "to reabsorb filtered hco3", "hco3 from", "from urine leading", "urine leading to", "leading to urinary hco3", "urinary hco3 wasting", "hco3 wasting and", "wasting and subsequent acidemia.", "and subsequent acidemia. hco3", "acidemia. hco3 also", "hco3 also needs", "also needs to move", "needs to move out", "to move out of", "move out of cells", "out of cells in", "of cells in the", "cells in the eye", "the eye thus", "eye thus failure", "thus failure to do", "failure to do so", "to do so can", "do so can affect", "so can affect ocular", "can affect ocular pressure", "affect ocular pressure homeostasis", "pressure homeostasis horita", "homeostasis horita et", "horita et al. 2005", "al. 2005 kurtz", "2005 kurtz &", "kurtz & zhu 2013", "zhu 2013 kurtz", "2013 kurtz &", "kurtz & zhu 2013b", "zhu 2013b seki", "2013b seki et", "seki et al. 2013", "et al. 2013 .", "4 5 7", "5 7 and 9", "7 and 9 of the", "and 9 of the slc4a", "9 of the slc4a family", "of the slc4a family couple", "the slc4a family couple the", "slc4a family couple the transport", "family couple the transport of", "couple the transport of bicarbonate", "transport of bicarbonate hco3", "hco3 with sodium", "with sodium ions na+", "sodium ions na+ .", "ions na+ . slc4a4", "na+ . slc4a4 aka", ". slc4a4 aka nbce1", "aka nbce1 is an", "nbce1 is an electrogenic", "an electrogenic na+/hco3 cotransporter", "electrogenic na+/hco3 cotransporter with", "na+/hco3 cotransporter with a", "cotransporter with a stoichiometry of", "with a stoichiometry of 1:3.", "a stoichiometry of 1:3. slc4a4", "stoichiometry of 1:3. slc4a4 is", "of 1:3. slc4a4 is expressed", "1:3. slc4a4 is expressed in", "slc4a4 is expressed in the", "is expressed in the kidney", "expressed in the kidney and", "in the kidney and pancreas", "kidney and pancreas with", "and pancreas with lesser", "pancreas with lesser expression", "with lesser expression in many", "lesser expression in many other", "expression in many other tissues.", "in many other tissues. mutations", "many other tissues. mutations in", "other tissues. mutations in slc4a4", "tissues. mutations in slc4a4 can", "mutations in slc4a4 can cause", "in slc4a4 can cause permanent", "slc4a4 can cause permanent isolated", "can cause permanent isolated proximal", "cause permanent isolated proximal renal", "permanent isolated proximal renal tubular", "isolated proximal renal tubular acidosis", "proximal renal tubular acidosis with", "renal tubular acidosis with ocular", "tubular acidosis with ocular abnormalities", "acidosis with ocular abnormalities and", "prta oa a", "oa a rare", "a rare autosomal recessive syndrome", "rare autosomal recessive syndrome characterised", "autosomal recessive syndrome characterised by", "recessive syndrome characterised by short", "syndrome characterised by short stature", "by short stature proximal", "short stature proximal renal", "stature proximal renal tubular", "renal tubular acidosis mental", "tubular acidosis mental retardation", "mental retardation bilateral glaucoma", "bilateral glaucoma cataracts and", "glaucoma cataracts and bandkeratopathy.", "cataracts and bandkeratopathy. prta results", "and bandkeratopathy. prta results from", "bandkeratopathy. prta results from the", "prta results from the failure", "results from the failure of", "from the failure of the", "the failure of the proximal", "failure of the proximal tubular", "of the proximal tubular cells", "the proximal tubular cells to", "proximal tubular cells to reabsorb", "tubular cells to reabsorb filtered", "cells to reabsorb filtered hco3", "filtered hco3 from", "hco3 from urine", "from urine leading to", "urine leading to urinary", "to urinary hco3 wasting", "urinary hco3 wasting and", "hco3 wasting and subsequent", "wasting and subsequent acidemia. hco3", "subsequent acidemia. hco3 also", "acidemia. hco3 also needs", "hco3 also needs to", "also needs to move out", "needs to move out of", "to move out of cells", "move out of cells in", "out of cells in the", "of cells in the eye", "in the eye thus", "the eye thus failure", "eye thus failure to", "thus failure to do so", "failure to do so can", "to do so can affect", "do so can affect ocular", "so can affect ocular pressure", "can affect ocular pressure homeostasis", "ocular pressure homeostasis horita", "pressure homeostasis horita et", "homeostasis horita et al.", "et al. 2005 kurtz", "al. 2005 kurtz &", "2005 kurtz & zhu", "& zhu 2013 kurtz", "zhu 2013 kurtz &", "2013 kurtz & zhu", "& zhu 2013b seki", "zhu 2013b seki et", "2013b seki et al.", "seki et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1728", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619055", "r hsa", "hsa 5619055", "r hsa 5619055" ] }, { "record_id": "GLY_000594_1_1728", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc24a4", "slc24a4 causes", "causes hypomineralized", "hypomineralized amelogenesis", "amelogenesis imperfecta", "defective slc24a4 causes", "slc24a4 causes hypomineralized", "causes hypomineralized amelogenesis", "hypomineralized amelogenesis imperfecta", "imperfecta ai", "defective slc24a4 causes hypomineralized", "slc24a4 causes hypomineralized amelogenesis", "causes hypomineralized amelogenesis imperfecta", "amelogenesis imperfecta ai", "defective slc24a4 causes hypomineralized amelogenesis", "slc24a4 causes hypomineralized amelogenesis imperfecta", "hypomineralized amelogenesis imperfecta ai", "the five", "five members", "members of", "of the", "the nckx", "family are", "are all", "all able", "able to", "to exchange", "exchange one", "one ca2+", "ca2+ and", "and one", "one k+", "k+ for", "for four", "four na+.", "na+. slc24a4", "slc24a4 encodes", "encodes an", "an exchanger", "exchanger protein", "protein nckx4", "nckx4 which", "which may", "may play", "play a", "a role", "role in", "in calcium", "calcium transport", "transport during", "during amelogenesis", "the process", "process of", "of formation", "formation of", "of tooth", "tooth enamel", "enamel .", ". slc24a4", "slc24a4 is", "is upregulated", "upregulated in", "in ameloblasts", "ameloblasts during", "during the", "the maturation", "maturation stage", "stage of", "of amelogenesis", "hu et", "et al.", "al. 2012", "2012 .", ". defects", "defects in", "in slc24a4", "slc24a4 can", "can cause", "cause hypomineralised", "hypomineralised amelogenesis", "an autosomal", "autosomal recessive", "recessive disorder", "disorder in", "in which", "which tooth", "enamel formation", "formation fails.", "fails. screening", "screening of", "of ai", "ai families", "families identified", "identified mutations", "mutations which", "which severely", "severely diminish", "diminish or", "or abolish", "abolish transport", "transport function", "function of", "of slc24a4", "parry et", "al. 2013", "wang et", "al. 2014", "2014 .

              genetic", ".

              genetic variants", "variants in", "slc24a4 define", "define the", "the skin/hair/eye", "skin/hair/eye pigmentation", "pigmentation variation", "variation locus", "locus 6", "mim:210750 .", "210750 .", ". in", "in a", "a genomewide", "genomewide association", "association scan", "scan of", "of thousands", "thousands of", "of icelanders", "icelanders and", "and dutch", "sulem et", "al. found", "found a", "a strong", "strong association", "association between", "between the", "the t", "t allele", "allele of", "of a", "a snp", "snp in", "in the", "the slc24a4", "slc24a4 gene", "gene and", "and blond", "blond versus", "versus brown", "brown hair", "hair and", "and blue", "blue versus", "versus green", "green eyes", "al. 2007", "2007 .", "the five members", "five members of", "members of the", "of the nckx", "nckx slc24", "slc24 family", "family are all", "are all able", "all able to", "able to exchange", "to exchange one", "exchange one ca2+", "one ca2+ and", "ca2+ and one", "and one k+", "one k+ for", "k+ for four", "for four na+.", "four na+. slc24a4", "na+. slc24a4 encodes", "slc24a4 encodes an", "encodes an exchanger", "an exchanger protein", "exchanger protein nckx4", "protein nckx4 which", "nckx4 which may", "which may play", "may play a", "play a role", "a role in", "role in calcium", "in calcium transport", "calcium transport during", "transport during amelogenesis", "amelogenesis the", "the process of", "process of formation", "of formation of", "formation of tooth", "of tooth enamel", "tooth enamel .", "enamel . slc24a4", ". slc24a4 is", "slc24a4 is upregulated", "is upregulated in", "upregulated in ameloblasts", "in ameloblasts during", "ameloblasts during the", "during the maturation", "the maturation stage", "maturation stage of", "stage of amelogenesis", "amelogenesis hu", "hu et al.", "et al. 2012", "al. 2012 .", "2012 . defects", ". defects in", "defects in slc24a4", "in slc24a4 can", "slc24a4 can cause", "can cause hypomineralised", "cause hypomineralised amelogenesis", "hypomineralised amelogenesis imperfecta", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder in", "disorder in which", "in which tooth", "which tooth enamel", "tooth enamel formation", "enamel formation fails.", "formation fails. screening", "fails. screening of", "screening of ai", "of ai families", "ai families identified", "families identified mutations", "identified mutations which", "mutations which severely", "which severely diminish", "severely diminish or", "diminish or abolish", "or abolish transport", "abolish transport function", "transport function of", "function of slc24a4", "slc24a4 parry", "parry et al.", "et al. 2013", "2013 wang", "wang et al.", "et al. 2014", "al. 2014 .

              genetic", "2014 .

              genetic variants", ".

              genetic variants in", "variants in slc24a4", "in slc24a4 define", "slc24a4 define the", "define the skin/hair/eye", "the skin/hair/eye pigmentation", "skin/hair/eye pigmentation variation", "pigmentation variation locus", "variation locus 6", "6 shep6", "shep6 mim:210750", "mim:210750 . in", "210750 . in", ". in a", "in a genomewide", "a genomewide association", "genomewide association scan", "association scan of", "scan of thousands", "of thousands of", "thousands of icelanders", "of icelanders and", "icelanders and dutch", "dutch sulem", "sulem et al.", "et al. found", "al. found a", "found a strong", "a strong association", "strong association between", "association between the", "between the t", "the t allele", "t allele of", "allele of a", "of a snp", "a snp in", "snp in the", "in the slc24a4", "the slc24a4 gene", "slc24a4 gene and", "gene and blond", "and blond versus", "blond versus brown", "versus brown hair", "brown hair and", "hair and blue", "and blue versus", "blue versus green", "versus green eyes", "eyes sulem", "et al. 2007", "al. 2007 .", "the five members of", "five members of the", "members of the nckx", "the nckx slc24", "slc24 family are", "family are all able", "are all able to", "all able to exchange", "able to exchange one", "to exchange one ca2+", "exchange one ca2+ and", "one ca2+ and one", "ca2+ and one k+", "and one k+ for", "one k+ for four", "k+ for four na+.", "for four na+. slc24a4", "four na+. slc24a4 encodes", "na+. slc24a4 encodes an", "slc24a4 encodes an exchanger", "encodes an exchanger protein", "an exchanger protein nckx4", "exchanger protein nckx4 which", "protein nckx4 which may", "nckx4 which may play", "which may play a", "may play a role", "play a role in", "a role in calcium", "role in calcium transport", "in calcium transport during", "calcium transport during amelogenesis", "during amelogenesis the", "amelogenesis the process", "the process of formation", "process of formation of", "of formation of tooth", "formation of tooth enamel", "of tooth enamel .", "tooth enamel . slc24a4", "enamel . slc24a4 is", ". slc24a4 is upregulated", "slc24a4 is upregulated in", "is upregulated in ameloblasts", "upregulated in ameloblasts during", "in ameloblasts during the", "ameloblasts during the maturation", "during the maturation stage", "the maturation stage of", "maturation stage of amelogenesis", "of amelogenesis hu", "amelogenesis hu et", "hu et al. 2012", "et al. 2012 .", "al. 2012 . defects", "2012 . defects in", ". defects in slc24a4", "defects in slc24a4 can", "in slc24a4 can cause", "slc24a4 can cause hypomineralised", "can cause hypomineralised amelogenesis", "cause hypomineralised amelogenesis imperfecta", "ai an", "an autosomal recessive disorder", "autosomal recessive disorder in", "recessive disorder in which", "disorder in which tooth", "in which tooth enamel", "which tooth enamel formation", "tooth enamel formation fails.", "enamel formation fails. screening", "formation fails. screening of", "fails. screening of ai", "screening of ai families", "of ai families identified", "ai families identified mutations", "families identified mutations which", "identified mutations which severely", "mutations which severely diminish", "which severely diminish or", "severely diminish or abolish", "diminish or abolish transport", "or abolish transport function", "abolish transport function of", "transport function of slc24a4", "of slc24a4 parry", "slc24a4 parry et", "parry et al. 2013", "al. 2013 wang", "2013 wang et", "wang et al. 2014", "et al. 2014 .

              genetic", "al. 2014 .

              genetic variants", "2014 .

              genetic variants in", ".

              genetic variants in slc24a4", "variants in slc24a4 define", "in slc24a4 define the", "slc24a4 define the skin/hair/eye", "define the skin/hair/eye pigmentation", "the skin/hair/eye pigmentation variation", "skin/hair/eye pigmentation variation locus", "pigmentation variation locus 6", "locus 6 shep6", "shep6 mim:210750 .", "mim:210750 . in a", "210750 . in a", ". in a genomewide", "in a genomewide association", "a genomewide association scan", "genomewide association scan of", "association scan of thousands", "scan of thousands of", "of thousands of icelanders", "thousands of icelanders and", "of icelanders and dutch", "and dutch sulem", "dutch sulem et", "sulem et al. found", "et al. found a", "al. found a strong", "found a strong association", "a strong association between", "strong association between the", "association between the t", "between the t allele", "the t allele of", "t allele of a", "allele of a snp", "of a snp in", "a snp in the", "snp in the slc24a4", "in the slc24a4 gene", "the slc24a4 gene and", "slc24a4 gene and blond", "gene and blond versus", "and blond versus brown", "blond versus brown hair", "versus brown hair and", "brown hair and blue", "hair and blue versus", "and blue versus green", "blue versus green eyes", "green eyes sulem", "eyes sulem et", "sulem et al. 2007", "et al. 2007 .", "the five members of the", "five members of the nckx", "of the nckx slc24", "nckx slc24 family", "slc24 family are all", "family are all able to", "are all able to exchange", "all able to exchange one", "able to exchange one ca2+", "to exchange one ca2+ and", "exchange one ca2+ and one", "one ca2+ and one k+", "ca2+ and one k+ for", "and one k+ for four", "one k+ for four na+.", "k+ for four na+. slc24a4", "for four na+. slc24a4 encodes", "four na+. slc24a4 encodes an", "na+. slc24a4 encodes an exchanger", "slc24a4 encodes an exchanger protein", "encodes an exchanger protein nckx4", "an exchanger protein nckx4 which", "exchanger protein nckx4 which may", "protein nckx4 which may play", "nckx4 which may play a", "which may play a role", "may play a role in", "play a role in calcium", "a role in calcium transport", "role in calcium transport during", "in calcium transport during amelogenesis", "transport during amelogenesis the", "during amelogenesis the process", "amelogenesis the process of", "the process of formation of", "process of formation of tooth", "of formation of tooth enamel", "formation of tooth enamel .", "of tooth enamel . slc24a4", "tooth enamel . slc24a4 is", "enamel . slc24a4 is upregulated", ". slc24a4 is upregulated in", "slc24a4 is upregulated in ameloblasts", "is upregulated in ameloblasts during", "upregulated in ameloblasts during the", "in ameloblasts during the maturation", "ameloblasts during the maturation stage", "during the maturation stage of", "the maturation stage of amelogenesis", "stage of amelogenesis hu", "of amelogenesis hu et", "amelogenesis hu et al.", "hu et al. 2012 .", "et al. 2012 . defects", "al. 2012 . defects in", "2012 . defects in slc24a4", ". defects in slc24a4 can", "defects in slc24a4 can cause", "in slc24a4 can cause hypomineralised", "slc24a4 can cause hypomineralised amelogenesis", "can cause hypomineralised amelogenesis imperfecta", "hypomineralised amelogenesis imperfecta ai", "ai an autosomal", "an autosomal recessive disorder in", "autosomal recessive disorder in which", "recessive disorder in which tooth", "disorder in which tooth enamel", "in which tooth enamel formation", "which tooth enamel formation fails.", "tooth enamel formation fails. screening", "enamel formation fails. screening of", "formation fails. screening of ai", "fails. screening of ai families", "screening of ai families identified", "of ai families identified mutations", "ai families identified mutations which", "families identified mutations which severely", "identified mutations which severely diminish", "mutations which severely diminish or", "which severely diminish or abolish", "severely diminish or abolish transport", "diminish or abolish transport function", "or abolish transport function of", "abolish transport function of slc24a4", "function of slc24a4 parry", "of slc24a4 parry et", "slc24a4 parry et al.", "et al. 2013 wang", "al. 2013 wang et", "2013 wang et al.", "wang et al. 2014 .

              genetic", "et al. 2014 .

              genetic variants", "al. 2014 .

              genetic variants in", "2014 .

              genetic variants in slc24a4", ".

              genetic variants in slc24a4 define", "variants in slc24a4 define the", "in slc24a4 define the skin/hair/eye", "slc24a4 define the skin/hair/eye pigmentation", "define the skin/hair/eye pigmentation variation", "the skin/hair/eye pigmentation variation locus", "skin/hair/eye pigmentation variation locus 6", "variation locus 6 shep6", "6 shep6 mim:210750", "shep6 mim:210750 . in", "mim:210750 . in a genomewide", "210750 . in a genomewide", ". in a genomewide association", "in a genomewide association scan", "a genomewide association scan of", "genomewide association scan of thousands", "association scan of thousands of", "scan of thousands of icelanders", "of thousands of icelanders and", "thousands of icelanders and dutch", "icelanders and dutch sulem", "and dutch sulem et", "dutch sulem et al.", "sulem et al. found a", "et al. found a strong", "al. found a strong association", "found a strong association between", "a strong association between the", "strong association between the t", "association between the t allele", "between the t allele of", "the t allele of a", "t allele of a snp", "allele of a snp in", "of a snp in the", "a snp in the slc24a4", "snp in the slc24a4 gene", "in the slc24a4 gene and", "the slc24a4 gene and blond", "slc24a4 gene and blond versus", "gene and blond versus brown", "and blond versus brown hair", "blond versus brown hair and", "versus brown hair and blue", "brown hair and blue versus", "hair and blue versus green", "and blue versus green eyes", "versus green eyes sulem", "green eyes sulem et", "eyes sulem et al.", "sulem et al. 2007 ." ] }, { "record_id": "GLY_000594_1_1729", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619062", "r hsa", "hsa 5619062", "r hsa 5619062" ] }, { "record_id": "GLY_000594_1_1729", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc1a3", "slc1a3 causes", "causes episodic", "episodic ataxia", "ataxia 6", "defective slc1a3 causes", "slc1a3 causes episodic", "causes episodic ataxia", "episodic ataxia 6", "6 ea6", "defective slc1a3 causes episodic", "slc1a3 causes episodic ataxia", "causes episodic ataxia 6", "ataxia 6 ea6", "defective slc1a3 causes episodic ataxia", "slc1a3 causes episodic ataxia 6", "episodic ataxia 6 ea6", "there are", "are two", "two classes", "classes of", "of glutamate", "glutamate transporters", "the excitatory", "excitatory amino", "amino acid", "acid transporters", "which depend", "depend on", "on an", "an electrochemical", "electrochemical gradient", "gradient of", "of na+", "na+ ions", "ions and", "and vesicular", "vesicular glutamate", "which are", "are proton", "proton dependent.", "dependent. together", "these transporters", "transporters uptake", "uptake and", "and release", "release glutamate", "glutamate to", "to mediate", "mediate this", "this neurotransmitter's", "neurotransmitter's excitatory", "excitatory signal", "signal and", "and are", "are part", "part of", "of the", "the glutamate", "glutamate gluatamine", "gluatamine cycle.

              the", "cycle.

              the slc1", "slc1 gene", "gene family", "family includes", "includes five", "five high", "high affinity", "affinity glutamate", "transporters encoded", "encoded by", "by slc1", "6 and", "and 7.", "7. these", "transporters can", "can mediate", "mediate transport", "transport of", "of l", "l glutamate", "l glu", "l aspartate", "l asp", "and d", "d aspartate", "d asp", "with cotransport", "cotransport of", "of 3", "3 na+", "and h+", "h+ and", "and antiport", "antiport of", "of a", "a k+", "k+ ion.", "ion. this", "this mechanism", "mechanism allows", "allows glutamate", "glutamate into", "into cells", "cells against", "against a", "a concentration", "concentration gradient.", "gradient. this", "this is", "is a", "a crucial", "crucial factor", "factor in", "in the", "the protection", "protection of", "of neurons", "neurons against", "against glutamate", "glutamate excitotoxicity", "the excitation", "excitation of", "of nerve", "nerve cells", "cells to", "to their", "their death", "the cns", "zhou &", "& danbolt", "danbolt 2014", "2014 .

              slc1a3", ".

              slc1a3 is", "is highly", "highly expressed", "expressed in", "the cerebellum", "cerebellum but", "but also", "also found", "found in", "the frontal", "frontal cortex", "hippocampus and", "and basal", "basal ganglia.", "ganglia. defects", "defects in", "in slc1a3", "slc1a3 have", "have been", "been shown", "shown to", "to cause", "cause episodic", "ataxia type", "type 6", "where mutations", "mutations in", "slc1a3 can", "can lead", "lead to", "to decreased", "decreased glutamate", "glutamate uptake", "thus contributing", "contributing to", "to neuronal", "neuronal hyperexcitability", "hyperexcitability to", "cause seizures", "hemiplegia and", "and episodic", "jen et", "et al.", "al. 2005", "de vries", "vries et", "al. 2009", "2009 .", "there are two", "are two classes", "two classes of", "classes of glutamate", "of glutamate transporters", "transporters the", "the excitatory amino", "excitatory amino acid", "amino acid transporters", "transporters eaats", "eaats which", "which depend on", "depend on an", "on an electrochemical", "an electrochemical gradient", "electrochemical gradient of", "gradient of na+", "of na+ ions", "na+ ions and", "ions and vesicular", "and vesicular glutamate", "vesicular glutamate transporters", "transporters vgluts", "vgluts which", "which are proton", "are proton dependent.", "proton dependent. together", "together these", "these transporters uptake", "transporters uptake and", "uptake and release", "and release glutamate", "release glutamate to", "glutamate to mediate", "to mediate this", "mediate this neurotransmitter's", "this neurotransmitter's excitatory", "neurotransmitter's excitatory signal", "excitatory signal and", "signal and are", "and are part", "are part of", "part of the", "of the glutamate", "the glutamate gluatamine", "glutamate gluatamine cycle.

              the", "gluatamine cycle.

              the slc1", "cycle.

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              slc1a3", "2014 .

              slc1a3 is", ".

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              the", "glutamate gluatamine cycle.

              the slc1", "gluatamine cycle.

              the slc1 gene", "cycle.

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              slc1a3", "danbolt 2014 .

              slc1a3 is", "2014 .

              slc1a3 is highly", ".

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              the", "the glutamate gluatamine cycle.

              the slc1", "glutamate gluatamine cycle.

              the slc1 gene", "gluatamine cycle.

              the slc1 gene family", "cycle.

              the slc1 gene family includes", "slc1 gene family includes five", "gene family includes five high", "family includes five high affinity", "includes five high affinity glutamate", "five high affinity glutamate transporters", "high affinity glutamate transporters encoded", "affinity glutamate transporters encoded by", "glutamate transporters encoded by slc1", "encoded by slc1 2", "slc1 2 3", "2 3 6", "3 6 and 7.", "6 and 7. these transporters", "and 7. these transporters can", "7. these transporters can mediate", "these transporters can mediate transport", "transporters can mediate transport of", "can mediate transport of l", "mediate transport of l glutamate", "of l glutamate l", "l glutamate l glu", "l glu l", "glu l aspartate", "l aspartate l asp", "l asp and d", "asp and d aspartate", "and d aspartate d", "d aspartate d asp", "d asp with cotransport", "asp with cotransport of", "with cotransport of 3 na+", "cotransport of 3 na+ ions", "of 3 na+ ions and", "3 na+ ions and h+", "na+ ions and h+ and", "ions and h+ and antiport", "and h+ and antiport of", "h+ and antiport of a", "and antiport of a k+", "antiport of a k+ ion.", "of a k+ ion. this", "a k+ ion. this mechanism", "k+ ion. this mechanism allows", "ion. this mechanism allows glutamate", "this mechanism allows glutamate into", "mechanism allows glutamate into cells", "allows glutamate into cells against", "glutamate into cells against a", "into cells against a concentration", "cells against a concentration gradient.", "against a concentration gradient. this", "a concentration gradient. this is", "concentration gradient. this is a", "gradient. this is a crucial", "this is a crucial factor", "is a crucial factor in", "a crucial factor in the", "crucial factor in the protection", "factor in the protection of", "in the protection of neurons", "the protection of neurons against", "protection of neurons against glutamate", "of neurons against glutamate excitotoxicity", "against glutamate excitotoxicity the", "glutamate excitotoxicity the excitation", "excitotoxicity the excitation of", "the excitation of nerve cells", "excitation of nerve cells to", "of nerve cells to their", "nerve cells to their death", "to their death in", "their death in the", "death in the cns", "in the cns zhou", "the cns zhou &", "cns zhou & danbolt", "zhou & danbolt 2014 .

              slc1a3", "& danbolt 2014 .

              slc1a3 is", "danbolt 2014 .

              slc1a3 is highly", "2014 .

              slc1a3 is highly expressed", ".

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slc1a3 can lead", "in slc1a3 can lead to", "slc1a3 can lead to decreased", "can lead to decreased glutamate", "lead to decreased glutamate uptake", "decreased glutamate uptake thus", "glutamate uptake thus contributing", "uptake thus contributing to", "thus contributing to neuronal hyperexcitability", "contributing to neuronal hyperexcitability to", "to neuronal hyperexcitability to cause", "neuronal hyperexcitability to cause seizures", "to cause seizures hemiplegia", "cause seizures hemiplegia and", "seizures hemiplegia and episodic", "and episodic ataxia jen", "episodic ataxia jen et", "ataxia jen et al.", "et al. 2005 de", "al. 2005 de vries", "2005 de vries et", "de vries et al. 2009", "vries et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1730", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619063", "r hsa", "hsa 5619063", "r hsa 5619063" ] }, { "record_id": "GLY_000594_1_1730", "filename": 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              the", "of protons.

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1998 . mutations and/or", "1998 . mutations and/or reduced", ". mutations and/or reduced expression", "mutations and/or reduced expression of", "and/or reduced expression of slc22a18", "reduced expression of slc22a18 have", "expression of slc22a18 have been", "of slc22a18 have been found", "slc22a18 have been found in", "have been found in certain", "been found in certain tumors", "found in certain tumors such", "in certain tumors such as", "certain tumors such as lung", "tumors such as lung cancer", "as lung cancer lncr", "cancer lncr mim:211980", "mim:211980 lee et", "211980 lee et", "et al. 1998 and", "al. 1998 and embryonal", "1998 and embryonal rhabdomyosarcoma", "1 rmse1 mim:268210", "mim:268210 schwienbacher et", "268210 schwienbacher et", "schwienbacher et al. 1998 .", "et al. 1998 . how", "al. 1998 . how slc22a18", "1998 . how slc22a18 might", ". how slc22a18 might be", "how slc22a18 might be involved", "slc22a18 might be involved in", "might be involved in growth", "be involved in growth regulation", "involved in growth regulation is", "in growth regulation is poorly", "growth regulation is poorly understood.", "regulation is poorly understood. there", "is poorly understood. there is", "poorly understood. there is speculation", "understood. there is speculation that", "there is speculation that it", "is speculation that it may", "speculation that it may be", "that it may be involved", "it may be involved in", "may be involved in resistance", "be involved in resistance to", "involved in resistance to chemotherapy", "in resistance to chemotherapy drugs", "resistance to chemotherapy drugs and/or", "to chemotherapy drugs and/or in", "chemotherapy drugs and/or in the", "drugs and/or in the export", "and/or in the export of", "in the export of genotoxic", "the export of genotoxic substances", "export of genotoxic substances whose", "of genotoxic substances whose retention", "genotoxic substances whose retention may", "substances whose retention may increase", "whose retention may increase the", "retention may increase the risk", "may increase the risk of", "increase the risk of tumor", "the risk of tumor formation." ] }, { "record_id": "GLY_000594_1_1732", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619067", "r hsa", "hsa 5619067", "r hsa 5619067" ] }, { "record_id": "GLY_000594_1_1732", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc1a1", "slc1a1 is", "is implicated", "implicated in", "in schizophrenia", "schizophrenia 18", "and dicarboxylic", "dicarboxylic aminoaciduria", "defective slc1a1 is", "slc1a1 is implicated", "is implicated in", "implicated in schizophrenia", "in schizophrenia 18", "18 sczd18", "sczd18 and", "and dicarboxylic aminoaciduria", "aminoaciduria dcbxa", "defective slc1a1 is implicated", "slc1a1 is implicated in", "is implicated in schizophrenia", "implicated in schizophrenia 18", "schizophrenia 18 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              a", ".

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              slc1a1", "2014 .

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              the", "glutamate glutamine cycle.

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              slc1a1", "danbolt 2014 .

              slc1a1 encodes", "2014 .

              slc1a1 encodes an", ".

              slc1a1 encodes an excitatory", "encodes an excitatory amino", "an excitatory amino acid", "excitatory amino acid carrier", "amino acid carrier 1", "carrier 1 eaac1", "eaac1 also called", "called eaat3 and", "eaat3 and is", "and is abundant particularly", "is abundant particularly in", "abundant particularly in brain", "particularly in brain but", "in brain but also", "brain but also in", "but also in kidney", "in kidney liver", "ovary testis and", "testis and in retinoblastoma", "and in retinoblastoma cell", "in retinoblastoma cell lines.", "retinoblastoma cell lines. in", "cell lines. in the", "lines. in the kidney", "the kidney slc1a1", "kidney slc1a1 is", "slc1a1 is present at", "is present at apical", "present at apical membranes", "at apical membranes of", "apical membranes of proximal", "membranes of proximal tubes", "of proximal tubes where", "proximal tubes where it", "tubes where it serves", "where it serves as", "it serves as a", "serves as a major", "as a major route", "a major route of", "major route of glutamate", "route of glutamate and", "of glutamate and aspartate", "glutamate and aspartate reuptake", "and aspartate reuptake from", "aspartate reuptake from urine.", "reuptake from urine. defects", "from urine. defects in", "urine. defects in slc1a1", "defects in slc1a1 are", "in slc1a1 are the", "slc1a1 are the cause", "are the cause of", "the cause of dicarboxylic", "cause of dicarboxylic aminoaciduria", "mim:222730 an", "222730 an", "autosomal recessive glutamate", "recessive glutamate aspartate", "glutamate aspartate transport defect", "aspartate transport defect in", "transport defect in the", "defect in the kidney", "in the kidney and", "the kidney and intestine", "and intestine bailey", "intestine bailey et", "bailey et al. 2011", "et al. 2011 .", "al. 2011 . mutations", "2011 . mutations that", ". mutations that can", "mutations that can cause", "that can cause dcbxa", "can cause dcbxa are", "cause dcbxa are r445w", "dcbxa are r445w and", "are r445w and i395del", "and i395del bailey", "i395del bailey et", "et al. 2011 .

              a", "al. 2011 .

              a defect", "2011 .

              a defect in", ".

              a defect in slc1a1", "defect in slc1a1 is", "in slc1a1 is also", "slc1a1 is also implicated", "is also implicated in", "also implicated in schizophrenia", "sczd18 mim:615232 .", ". schizophrenia sczd", "mim:181500 is a", "181500 is a", "a complex multifactorial", "complex multifactorial psychotic", "multifactorial psychotic disorder characterised", "psychotic disorder characterised by", "disorder characterised by disturbances", "characterised by disturbances in", "by disturbances in the", "disturbances in the form", "in the form and", "the form and content", "form and content of", "and content of thought", "of thought in", "thought in mood", "in mood in", "mood in sense", "in sense of self", "sense of self and", "of self and relationship", "self and relationship to", "and relationship to the", "relationship to the external", "to the external world", "the external world and", "external world and in", "world and in behaviour.", "and in behaviour. it", "in behaviour. it ranks", "behaviour. it ranks amongst", "it ranks amongst the", "ranks amongst the world's", "amongst the world's top", "the world's top 10", "world's top 10 causes", "top 10 causes of", "10 causes of long", "causes of long term", "of long term disability.", "long term disability. at", "term disability. at the", "disability. at the neuropathological", "at the neuropathological level", "neuropathological level sczd", "level sczd appears", "sczd appears to be", "appears to be characterised", "to be characterised by", "be characterised by synaptic", "characterised by synaptic deficits", "synaptic deficits alterations", "deficits alterations in", "alterations in glutamate and", "in glutamate and dopamine", "glutamate and dopamine neurotransmission", "and dopamine neurotransmission and", "dopamine neurotransmission and hypofrontality", "and hypofrontality a", "hypofrontality a state", "a state of decreased", "state of decreased cerebral", "of decreased cerebral blood", "decreased cerebral blood flow", "blood flow cbf", "cbf in the", "in the prefrontal cortex", "the prefrontal cortex of", "prefrontal cortex of the", "cortex of the brain", "of the brain .", "the brain . variations", "brain . variations in", ". variations in the", "variations in the slc1a1", "in the slc1a1 gene", "the slc1a1 gene can", "slc1a1 gene can confer", "gene can confer susceptibility", "can confer susceptibility to", "confer susceptibility to sczd18", "to sczd18 harris", "sczd18 harris et", "harris et al. 2013", "et al. 2013 .", "al. 2013 . in", "2013 . in the", ". in the remote", "in the remote pacific", "the remote pacific island", "remote pacific island of", "pacific island of palau", "of palau the", "palau the risk", "the risk of sczd", "risk of sczd is", "of sczd is 2", "sczd is 2 3", "is 2 3 times", "2 3 times the", "3 times the worldwide", "times the worldwide rate.", "the worldwide rate. in", "worldwide rate. in a", "rate. in a 5", "in a 5 generation", "a 5 generation palauan", "5 generation palauan family", "palauan family an", "family an 84kb", "an 84kb deletion was", "84kb deletion was carried", "deletion was carried by", "was carried by psychosis", "carried by psychosis patients", "by psychosis patients and", "psychosis patients and proposed", "patients and proposed to", "and proposed to increase", "proposed to increase the", "to increase the disease", "increase the disease risk", "the disease risk more", "disease risk more than", "risk more than 18", "more than 18 fold", "than 18 fold for", "18 fold for family", "fold for family members", "family members myles", "members myles worsley", "myles worsley et al.", "worsley et al. 2013", "there are two classes of", "are two classes of glutamate", "two classes of glutamate transporters", "of glutamate transporters the", "glutamate transporters the excitatory", "transporters the excitatory amino", "the excitatory amino acid transporters", "amino acid transporters eaats", "transporters eaats which", "eaats which depend on", "which depend on an electrochemical", "depend on an electrochemical gradient", "on an electrochemical gradient of", "an electrochemical gradient of na+", "electrochemical gradient of na+ ions", "gradient of na+ ions and", "of na+ ions and vesicular", "na+ ions and vesicular glutamate", "ions and vesicular glutamate transporters", "vesicular glutamate transporters vgluts", "transporters vgluts which", "vgluts which are proton", "which are proton dependent. together", "proton dependent. together these", "dependent. together these transporters", "together these transporters uptake", "these transporters uptake and release", "transporters uptake and release glutamate", "uptake and release glutamate to", "and release glutamate to mediate", "release glutamate to mediate this", "glutamate to mediate this neurotransmitter's", "to mediate this neurotransmitter's excitatory", "mediate this neurotransmitter's excitatory signal", "this neurotransmitter's excitatory signal and", "neurotransmitter's excitatory signal and are", "excitatory signal and are part", "signal and are part of", "and are part of the", "are part of the glutamate", "part of the glutamate glutamine", "of the glutamate glutamine cycle.

              the", "the glutamate glutamine cycle.

              the slc1", "glutamate glutamine cycle.

              the slc1 gene", "glutamine cycle.

              the slc1 gene family", "cycle.

              the slc1 gene family includes", "slc1 gene family includes five", "gene family includes five high", "family includes five high affinity", "includes five high affinity glutamate", "five high affinity glutamate transporters", "high affinity glutamate transporters encoded", "affinity glutamate transporters encoded by", "glutamate transporters encoded by slc1", "encoded by slc1 2", "slc1 2 3", "2 3 6", "3 6 and 7.", "6 and 7. these transporters", "and 7. these transporters can", "7. these transporters can mediate", "these transporters can mediate transport", "transporters can mediate transport of", "can mediate transport of l", "mediate transport of l glutamate", "of l glutamate l", "l glutamate l glu", "l glu l", "glu l aspartate", "l aspartate l asp", "l asp and d", "asp and d aspartate", "and d aspartate d", "d aspartate d asp", "d asp with cotransport", "asp with cotransport of", "with cotransport of 3 na+", "cotransport of 3 na+ ions", "of 3 na+ ions and", "3 na+ ions and h+", "na+ ions and h+ and", "ions and h+ and antiport", "and h+ and antiport of", "h+ and antiport of a", "and antiport of a k+", "antiport of a k+ ion.", "of a k+ ion. this", "a k+ ion. this mechanism", "k+ ion. this mechanism allows", "ion. this mechanism allows glutamate", "this mechanism allows glutamate into", "mechanism allows glutamate into cells", "allows glutamate into cells against", "glutamate into cells against a", "into cells against a concentration", "cells against a concentration gradient.", "against a concentration gradient. this", "a concentration gradient. this is", "concentration gradient. this is a", "gradient. this is a crucial", "this is a crucial factor", "is a crucial factor in", "a crucial factor in the", "crucial factor in the protection", "factor in the protection of", "in the protection of neurons", "the protection of neurons against", "protection of neurons against glutamate", "of neurons against glutamate excitotoxicity", "against glutamate excitotoxicity the", "glutamate excitotoxicity the excitation", "excitotoxicity the excitation of", "the excitation of nerve cells", "excitation of nerve cells to", "of nerve cells to their", "nerve cells to their death", "to their death in", "their death in the", "death in the cns", "in the cns zhou", "the cns zhou &", "cns zhou & danbolt", "zhou & danbolt 2014 .

              slc1a1", "& danbolt 2014 .

              slc1a1 encodes", "danbolt 2014 .

              slc1a1 encodes an", "2014 .

              slc1a1 encodes an excitatory", ".

              slc1a1 encodes an excitatory amino", "encodes an excitatory amino acid", "an excitatory amino acid carrier", "excitatory amino acid carrier 1", "acid carrier 1 eaac1", "1 eaac1 also", "eaac1 also called eaat3", "also called eaat3 and", "called eaat3 and is", "eaat3 and is abundant", "and is abundant particularly in", "is abundant particularly in brain", "abundant particularly in brain but", "particularly in brain but also", "in brain but also in", "brain but also in kidney", "also in kidney liver", "kidney liver muscle", "liver muscle ovary", "muscle ovary testis", "ovary testis and in", "testis and in retinoblastoma cell", "and in retinoblastoma cell lines.", "in retinoblastoma cell lines. in", "retinoblastoma cell lines. in the", "cell lines. in the kidney", "in the kidney slc1a1", "the kidney slc1a1 is", "kidney slc1a1 is present", "slc1a1 is present at apical", "is present at apical membranes", "present at apical membranes of", "at apical membranes of proximal", "apical membranes of proximal tubes", "membranes of proximal tubes where", "of proximal tubes where it", "proximal tubes where it serves", "tubes where it serves as", "where it serves as a", "it serves as a major", "serves as a major route", "as a major route of", "a major route of glutamate", "major route of glutamate and", "route of glutamate and aspartate", "of glutamate and aspartate reuptake", "glutamate and aspartate reuptake from", "and aspartate reuptake from urine.", "aspartate reuptake from urine. defects", "reuptake from urine. defects in", "from urine. defects in slc1a1", "urine. defects in slc1a1 are", "defects in slc1a1 are the", "in slc1a1 are the cause", "slc1a1 are the cause of", "are the cause of dicarboxylic", "the cause of dicarboxylic aminoaciduria", "of dicarboxylic aminoaciduria dcbxa", "aminoaciduria dcbxa mim:222730", "mim:222730 an autosomal", "222730 an autosomal", "an autosomal recessive glutamate", "autosomal recessive glutamate aspartate", "recessive glutamate aspartate transport", "glutamate aspartate transport defect in", "aspartate transport defect in the", "transport defect in the kidney", "defect in the kidney and", "in the kidney and intestine", "kidney and intestine bailey", "and intestine bailey et", "intestine bailey et al.", "bailey et al. 2011 .", "et al. 2011 . mutations", "al. 2011 . mutations that", "2011 . mutations that can", ". mutations that can cause", "mutations that can cause dcbxa", "that can cause dcbxa are", "can cause dcbxa are r445w", "cause dcbxa are r445w and", "dcbxa are r445w and i395del", "r445w and i395del bailey", "and i395del bailey et", "i395del bailey et al.", "bailey et al. 2011 .

              a", "et al. 2011 .

              a defect", "al. 2011 .

              a defect in", "2011 .

              a defect in slc1a1", ".

              a defect in slc1a1 is", "defect in slc1a1 is also", "in slc1a1 is also implicated", "slc1a1 is also implicated in", "is also implicated in schizophrenia", "also implicated in schizophrenia 18", "18 sczd18 mim:615232", "sczd18 mim:615232 . schizophrenia", "mim:615232 . schizophrenia sczd", "615232 . schizophrenia sczd", "schizophrenia sczd mim:181500", "sczd mim:181500 is", "mim:181500 is a complex", "181500 is a complex", "is a complex multifactorial", "a complex multifactorial psychotic", "complex multifactorial psychotic disorder", "multifactorial psychotic disorder characterised by", "psychotic disorder characterised by disturbances", "disorder characterised by disturbances in", "characterised by disturbances in the", "by disturbances in the form", "disturbances in the form and", "in the form and content", "the form and content of", "form and content of thought", "content of thought in", "of thought in mood", "in mood in sense", "mood in sense of", "in sense of self and", "sense of self and relationship", "of self and relationship to", "self and relationship to the", "and relationship to the external", "relationship to the external world", "to the external world and", "the external world and in", "external world and in behaviour.", "world and in behaviour. it", "and in behaviour. it ranks", "in behaviour. it ranks amongst", "behaviour. it ranks amongst the", "it ranks amongst the world's", "ranks amongst the world's top", "amongst the world's top 10", "the world's top 10 causes", "world's top 10 causes of", "top 10 causes of long", "10 causes of long term", "causes of long term disability.", "of long term disability. at", "long term disability. at the", "term disability. at the neuropathological", "disability. at the neuropathological level", "the neuropathological level sczd", "neuropathological level sczd appears", "level sczd appears to", "sczd appears to be characterised", "appears to be characterised by", "to be characterised by synaptic", "be characterised by synaptic deficits", "by synaptic deficits alterations", "synaptic deficits alterations in", "deficits alterations in glutamate", "alterations in glutamate and dopamine", "in glutamate and dopamine neurotransmission", "glutamate and dopamine neurotransmission and", "and dopamine neurotransmission and hypofrontality", "neurotransmission and hypofrontality a", "and hypofrontality a state", "hypofrontality a state of", "a state of decreased cerebral", "state of decreased cerebral blood", "of decreased cerebral blood flow", "cerebral blood flow cbf", "flow cbf in", "cbf in the prefrontal", "in the prefrontal cortex of", "the prefrontal cortex of the", "prefrontal cortex of the brain", "cortex of the brain .", "of the brain . variations", "the brain . variations in", "brain . variations in the", ". variations in the slc1a1", "variations in the slc1a1 gene", "in the slc1a1 gene can", "the slc1a1 gene can confer", "slc1a1 gene can confer susceptibility", "gene can confer susceptibility to", "can confer susceptibility to sczd18", "susceptibility to sczd18 harris", "to sczd18 harris et", "sczd18 harris et al.", "harris et al. 2013 .", "et al. 2013 . in", "al. 2013 . in the", "2013 . in the remote", ". in the remote pacific", "in the remote pacific island", "the remote pacific island of", "remote pacific island of palau", "island of palau the", "of palau the risk", "palau the risk of", "the risk of sczd is", "risk of sczd is 2", "of sczd is 2 3", "sczd is 2 3 times", "is 2 3 times the", "2 3 times the worldwide", "3 times the worldwide rate.", "times the worldwide rate. in", "the worldwide rate. in a", "worldwide rate. in a 5", "rate. in a 5 generation", "in a 5 generation palauan", "a 5 generation palauan family", "generation palauan family an", "palauan family an 84kb", "family an 84kb deletion", "an 84kb deletion was carried", "84kb deletion was carried by", "deletion was carried by psychosis", "was carried by psychosis patients", "carried by psychosis patients and", "by psychosis patients and proposed", "psychosis patients and proposed to", "patients and proposed to increase", "and proposed to increase the", "proposed to increase the disease", "to increase the disease risk", "increase the disease risk more", "the disease risk more than", "disease risk more than 18", "risk more than 18 fold", "more than 18 fold for", "than 18 fold for family", "18 fold for family members", "for family members myles", "family members myles worsley", "members myles worsley et", "myles worsley et al. 2013", "worsley et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1733", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619070", "r hsa", "hsa 5619070", "r hsa 5619070" ] }, { "record_id": "GLY_000594_1_1733", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc16a1", "slc16a1 causes", "causes symptomatic", "symptomatic deficiency", "deficiency in", "in lactate", "lactate transport", "defective slc16a1 causes", "slc16a1 causes symptomatic", "causes symptomatic deficiency", "symptomatic deficiency in", "deficiency in lactate", "in lactate transport", "transport sdlt", "defective slc16a1 causes symptomatic", "slc16a1 causes symptomatic deficiency", "causes symptomatic deficiency in", "symptomatic deficiency in lactate", "deficiency in lactate transport", "lactate transport sdlt", "defective slc16a1 causes symptomatic deficiency", "slc16a1 causes symptomatic deficiency in", "causes symptomatic deficiency in lactate", "symptomatic deficiency in lactate transport", "in lactate transport sdlt", "four members", "members of", "of the", "the slc16a", "slc16a gene", "gene family", "family encode", "encode classical", "classical monocarboxylate", "monocarboxylate transporters", "transporters mct1", "mct1 4.", "4. widely", "widely expressed", "they all", "all function", "function as", "as proton", "proton dependent", "dependent transporters", "transporters of", "of monocarboxylic", "monocarboxylic acids", "acids such", "such as", "as lactate", "lactate and", "and pyruvate", "pyruvate and", "and ketone", "ketone bodies", "bodies such", "as acetacetate", "acetacetate and", "and beta", "beta hydroxybutyrate.", "hydroxybutyrate. these", "these processes", "processes are", "are crucial", "crucial in", "in the", "the regulation", "regulation of", "of energy", "energy metabolism", "metabolism and", "and acid", "acid base", "base homeostasis.

              slc16a1", "homeostasis.

              slc16a1 encodes", "encodes mct1", "a ubiquitiously", "ubiquitiously expressed", "expressed protein.", "protein. heterozygous", "heterozygous defects", "defects in", "in slc16a1", "slc16a1 were", "were found", "found in", "in patients", "patients with", "with symptomatic", "sdlt aka", "aka erythrocyte", "erythrocyte lactate", "lactate transporter", "transporter defect", "resulting in", "in an", "an acidic", "acidic intracellular", "intracellular environment", "environment and", "and muscle", "muscle degeneration", "degeneration with", "with the", "the release", "release of", "of myoglobin", "myoglobin and", "and creatine", "creatine kinase", "merezhinskaya et", "et al.", "al. 2000", "2000 .", ". this", "this defect", "defect could", "could compromise", "compromise extreme", "extreme performance", "performance in", "in otherwise", "otherwise healthy", "healthy individuals.

              slc16a1", "individuals.

              slc16a1 is", "is essential", "essential for", "for lactate", "transport in", "in muscle", "muscle cells.", "cells. it", "it is", "is also", "also highly", "highly enriched", "enriched in", "in astrocytes", "astrocytes and", "and oligodendroglia", "neuroglia that", "that support", "insulate and", "and provide", "provide energy", "energy metabolites", "metabolites to", "to axons.", "axons. oligodendroglia", "oligodendroglia dysfunction", "dysfunction can", "can lead", "lead to", "to axon", "axon degeneration", "degeneration in", "in several", "several diseases.", "diseases. the", "the cause", "cause is", "is unknown", "unknown but", "but disruption", "disruption of", "of slc16a1", "slc16a1 transporter", "transporter produces", "produces axon", "axon damage", "damage and", "and neuron", "neuron loss", "loss in", "in animal", "animal and", "and cell", "cell culture", "culture models.", "models. in", "in humans", "this transporter", "transporter is", "is reduced", "reduced in", "with amyotrophic", "amyotrophic lateral", "lateral sclerosis", "lee et", "al. 2012", "2012 .

              in", ".

              in cancer", "cancer cells", "a common", "common change", "change is", "is the", "the upregulation", "upregulation of", "of glycolysis.", "glycolysis. the", "the anti", "anti cancer", "cancer drug", "drug candidate", "candidate 3", "3 bromopyruvate", "3 brpa", "can inhibit", "inhibit glycolysis", "glycolysis through", "through its", "its uptake", "uptake into", "into cancer", "cells via", "via slc16a1", "slc16a1 so", "so it", "the main", "main determinant", "determinant of", "of 3", "brpa sensitivity", "sensitivity in", "in these", "these cells", "birsoy et", "al. 2013", "2013 .", "four members of", "members of the", "of the slc16a", "the slc16a gene", "slc16a gene family", "gene family encode", "family encode classical", "encode classical monocarboxylate", "classical monocarboxylate transporters", "monocarboxylate transporters mct1", "transporters mct1 4.", "mct1 4. widely", "4. widely expressed", "expressed they", "they all function", "all function as", "function as proton", "as proton dependent", "proton dependent transporters", "dependent transporters of", "transporters of monocarboxylic", "of monocarboxylic acids", "monocarboxylic acids such", "acids such as", "such as lactate", "as lactate and", "lactate and pyruvate", "and pyruvate and", "pyruvate and ketone", "and ketone bodies", "ketone bodies such", "bodies such as", "such as acetacetate", "as acetacetate and", "acetacetate and beta", "and beta hydroxybutyrate.", "beta hydroxybutyrate. these", "hydroxybutyrate. these processes", "these processes are", "processes are crucial", "are crucial in", "crucial in the", "in the regulation", "the regulation of", "regulation of energy", "of energy metabolism", "energy metabolism and", "metabolism and acid", "and acid base", "acid base homeostasis.

              slc16a1", "base homeostasis.

              slc16a1 encodes", "homeostasis.

              slc16a1 encodes mct1", "mct1 a", "a ubiquitiously expressed", "ubiquitiously expressed protein.", "expressed protein. heterozygous", "protein. heterozygous defects", "heterozygous defects in", "defects in slc16a1", "in slc16a1 were", "slc16a1 were found", "were found in", "found in patients", "in patients with", "patients with symptomatic", "with symptomatic deficiency", "sdlt aka erythrocyte", "aka erythrocyte lactate", "erythrocyte lactate transporter", "lactate transporter defect", "defect mim:245340", "resulting in an", "in an acidic", "an acidic intracellular", "acidic intracellular environment", "intracellular environment and", "environment and muscle", "and muscle degeneration", "muscle degeneration with", "degeneration with the", "with the release", "the release of", "release of myoglobin", "of myoglobin and", "myoglobin and creatine", "and creatine kinase", "kinase merezhinskaya", "merezhinskaya et al.", "et al. 2000", "al. 2000 .", "2000 . this", ". this defect", "this defect could", "defect could compromise", "could compromise extreme", "compromise extreme performance", "extreme performance in", "performance in otherwise", "in otherwise healthy", "otherwise healthy individuals.

              slc16a1", "healthy individuals.

              slc16a1 is", "individuals.

              slc16a1 is essential", "is essential for", "essential for lactate", "for lactate transport", "lactate transport in", "transport in muscle", "in muscle cells.", "muscle cells. it", "cells. it is", "it is also", "is also highly", "also highly enriched", "highly enriched in", "enriched in astrocytes", "in astrocytes and", "astrocytes and oligodendroglia", "oligodendroglia neuroglia", "neuroglia that support", "support insulate", "insulate and provide", "and provide energy", "provide energy metabolites", "energy metabolites to", "metabolites to axons.", "to axons. oligodendroglia", "axons. oligodendroglia dysfunction", "oligodendroglia dysfunction can", "dysfunction can lead", "can lead to", "lead to axon", "to axon degeneration", "axon degeneration in", "degeneration in several", "in several diseases.", "several diseases. the", "diseases. the cause", "the cause is", "cause is unknown", "is unknown but", "unknown but disruption", "but disruption of", "disruption of slc16a1", "of slc16a1 transporter", "slc16a1 transporter produces", "transporter produces axon", "produces axon damage", "axon damage and", "damage and neuron", "and neuron loss", "neuron loss in", "loss in animal", "in animal and", "animal and cell", "and cell culture", "cell culture models.", "culture models. in", "models. in humans", "humans this", "this transporter is", "transporter is reduced", "is reduced in", "reduced in patients", "patients with amyotrophic", "with amyotrophic lateral", "amyotrophic lateral sclerosis", "sclerosis lee", "lee et al.", "et al. 2012", "al. 2012 .

              in", "2012 .

              in cancer", ".

              in cancer cells", "cells a", "a common change", "common change is", "change is the", "is the upregulation", "the upregulation of", "upregulation of glycolysis.", "of glycolysis. the", "glycolysis. the anti", "the anti cancer", "anti cancer drug", "cancer drug candidate", "drug candidate 3", "candidate 3 bromopyruvate", "bromopyruvate 3", "brpa can", "can inhibit glycolysis", "inhibit glycolysis through", "glycolysis through its", "through its uptake", "its uptake into", "uptake into cancer", "into cancer cells", "cancer cells via", "cells via slc16a1", "via slc16a1 so", "slc16a1 so it", "so it is", "it is the", "is the main", "the main determinant", "main determinant of", "determinant of 3", "of 3 brpa", "3 brpa sensitivity", "brpa sensitivity in", "sensitivity in these", "in these cells", "cells birsoy", "birsoy et al.", "et al. 2013", "al. 2013 .", "four members of the", "members of the slc16a", "of the slc16a gene", "the slc16a gene family", "slc16a gene family encode", "gene family encode classical", "family encode classical monocarboxylate", "encode classical monocarboxylate transporters", "classical monocarboxylate transporters mct1", "monocarboxylate transporters mct1 4.", "transporters mct1 4. widely", "mct1 4. widely expressed", "widely expressed they", "expressed they all", "they all function as", "all function as proton", "function as proton dependent", "as proton dependent transporters", "proton dependent transporters of", "dependent transporters of monocarboxylic", "transporters of monocarboxylic acids", "of monocarboxylic acids such", "monocarboxylic acids such as", "acids such as lactate", "such as lactate and", "as lactate and pyruvate", "lactate and pyruvate and", "and pyruvate and ketone", "pyruvate and ketone bodies", "and ketone bodies such", "ketone bodies such as", "bodies such as acetacetate", "such as acetacetate and", "as acetacetate and beta", "acetacetate and beta hydroxybutyrate.", "and beta hydroxybutyrate. these", "beta hydroxybutyrate. these processes", "hydroxybutyrate. these processes are", "these processes are crucial", "processes are crucial in", "are crucial in the", "crucial in the regulation", "in the regulation of", "the regulation of energy", "regulation of energy metabolism", "of energy metabolism and", "energy metabolism and acid", "metabolism and acid base", "and acid base homeostasis.

              slc16a1", "acid base homeostasis.

              slc16a1 encodes", "base homeostasis.

              slc16a1 encodes mct1", "encodes mct1 a", "mct1 a ubiquitiously", "a ubiquitiously expressed protein.", "ubiquitiously expressed protein. heterozygous", "expressed protein. heterozygous defects", "protein. heterozygous defects in", "heterozygous defects in slc16a1", "defects in slc16a1 were", "in slc16a1 were found", "slc16a1 were found in", "were found in patients", "found in patients with", "in patients with symptomatic", "patients with symptomatic deficiency", "with symptomatic deficiency in", "transport sdlt aka", "sdlt aka erythrocyte lactate", "aka erythrocyte lactate transporter", "erythrocyte lactate transporter defect", "transporter defect mim:245340", "mim:245340 resulting", "245340 resulting", "resulting in an acidic", "in an acidic intracellular", "an acidic intracellular environment", "acidic intracellular environment and", "intracellular environment and muscle", "environment and muscle degeneration", "and muscle degeneration with", "muscle degeneration with the", "degeneration with the release", "with the release of", "the release of myoglobin", "release of myoglobin and", "of myoglobin and creatine", "myoglobin and creatine kinase", "creatine kinase merezhinskaya", "kinase merezhinskaya et", "merezhinskaya et al. 2000", "et al. 2000 .", "al. 2000 . this", "2000 . this defect", ". this defect could", "this defect could compromise", "defect could compromise extreme", "could compromise extreme performance", "compromise extreme performance in", "extreme performance in otherwise", "performance in otherwise healthy", "in otherwise healthy individuals.

              slc16a1", "otherwise healthy individuals.

              slc16a1 is", "healthy individuals.

              slc16a1 is essential", "individuals.

              slc16a1 is essential for", "is essential for lactate", "essential for lactate transport", "for lactate transport in", "lactate transport in muscle", "transport in muscle cells.", "in muscle cells. it", "muscle cells. it is", "cells. it is also", "it is also highly", "is also highly enriched", "also highly enriched in", "highly enriched in astrocytes", "enriched in astrocytes and", "in astrocytes and oligodendroglia", "and oligodendroglia neuroglia", "oligodendroglia neuroglia that", "that support insulate", "support insulate and", "insulate and provide energy", "and provide energy metabolites", "provide energy metabolites to", "energy metabolites to axons.", "metabolites to axons. oligodendroglia", "to axons. oligodendroglia dysfunction", "axons. oligodendroglia dysfunction can", "oligodendroglia dysfunction can lead", "dysfunction can lead to", "can lead to axon", "lead to axon degeneration", "to axon degeneration in", "axon degeneration in several", "degeneration in several diseases.", "in several diseases. the", "several diseases. the cause", "diseases. the cause is", "the cause is unknown", "cause is unknown but", "is unknown but disruption", "unknown but disruption of", "but disruption of slc16a1", "disruption of slc16a1 transporter", "of slc16a1 transporter produces", "slc16a1 transporter produces axon", "transporter produces axon damage", "produces axon damage and", "axon damage and neuron", "damage and neuron loss", "and neuron loss in", "neuron loss in animal", "loss in animal and", "in animal and cell", "animal and cell culture", "and cell culture models.", "cell culture models. in", "culture models. in humans", "in humans this", "humans this transporter", "this transporter is reduced", "transporter is reduced in", "is reduced in patients", "reduced in patients with", "in patients with amyotrophic", "patients with amyotrophic lateral", "with amyotrophic lateral sclerosis", "lateral sclerosis lee", "sclerosis lee et", "lee et al. 2012", "et al. 2012 .

              in", "al. 2012 .

              in cancer", "2012 .

              in cancer cells", "cancer cells a", "cells a common", "a common change is", "common change is the", "change is the upregulation", "is the upregulation of", "the upregulation of glycolysis.", "upregulation of glycolysis. the", "of glycolysis. the anti", "glycolysis. the anti cancer", "the anti cancer drug", "anti cancer drug candidate", "cancer drug candidate 3", "drug candidate 3 bromopyruvate", "3 bromopyruvate 3", "bromopyruvate 3 brpa", "3 brpa can", "brpa can inhibit", "can inhibit glycolysis through", "inhibit glycolysis through its", "glycolysis through its uptake", "through its uptake into", "its uptake into cancer", "uptake into cancer cells", "into cancer cells via", "cancer cells via slc16a1", "cells via slc16a1 so", "via slc16a1 so it", "slc16a1 so it is", "so it is the", "it is the main", "is the main determinant", "the main determinant of", "main determinant of 3", "determinant of 3 brpa", "of 3 brpa sensitivity", "3 brpa sensitivity in", "brpa sensitivity in these", "sensitivity in these cells", "these cells birsoy", "cells birsoy et", "birsoy et al. 2013", "et al. 2013 .", "four members of the slc16a", "members of the slc16a gene", "of the slc16a gene family", "the slc16a gene family encode", "slc16a gene family encode classical", "gene family encode classical monocarboxylate", "family encode classical monocarboxylate transporters", "encode classical monocarboxylate transporters mct1", "classical monocarboxylate transporters mct1 4.", "monocarboxylate transporters mct1 4. widely", "transporters mct1 4. widely expressed", "4. widely expressed they", "widely expressed they all", "expressed they all function", "they all function as proton", "all function as proton dependent", "function as proton dependent transporters", "as proton dependent transporters of", "proton dependent transporters of monocarboxylic", "dependent transporters of monocarboxylic acids", "transporters of monocarboxylic acids such", "of monocarboxylic acids such as", "monocarboxylic acids such as lactate", "acids such as lactate and", "such as lactate and pyruvate", "as lactate and pyruvate and", "lactate and pyruvate and ketone", "and pyruvate and ketone bodies", "pyruvate and ketone bodies such", "and ketone bodies such as", "ketone bodies such as acetacetate", "bodies such as acetacetate and", "such as acetacetate and beta", "as acetacetate and beta hydroxybutyrate.", "acetacetate and beta hydroxybutyrate. these", "and beta hydroxybutyrate. these processes", "beta hydroxybutyrate. these processes are", "hydroxybutyrate. these processes are crucial", "these processes are crucial in", "processes are crucial in the", "are crucial in the regulation", "crucial in the regulation of", "in the regulation of energy", "the regulation of energy metabolism", "regulation of energy metabolism and", "of energy metabolism and acid", "energy metabolism and acid base", "metabolism and acid base homeostasis.

              slc16a1", "and acid base homeostasis.

              slc16a1 encodes", "acid base homeostasis.

              slc16a1 encodes mct1", "homeostasis.

              slc16a1 encodes mct1 a", "encodes mct1 a ubiquitiously", "mct1 a ubiquitiously expressed", "a ubiquitiously expressed protein. heterozygous", "ubiquitiously expressed protein. heterozygous defects", "expressed protein. heterozygous defects in", "protein. heterozygous defects in slc16a1", "heterozygous defects in slc16a1 were", "defects in slc16a1 were found", "in slc16a1 were found in", "slc16a1 were found in patients", "were found in patients with", "found in patients with symptomatic", "in patients with symptomatic deficiency", "patients with symptomatic deficiency in", "with symptomatic deficiency in lactate", "lactate transport sdlt aka", "transport sdlt aka erythrocyte", "sdlt aka erythrocyte lactate transporter", "aka erythrocyte lactate transporter defect", "lactate transporter defect mim:245340", "mim:245340 resulting in", "245340 resulting in", "resulting in an acidic intracellular", "in an acidic intracellular environment", "an acidic intracellular environment and", "acidic intracellular environment and muscle", "intracellular environment and muscle degeneration", "environment and muscle degeneration with", "and muscle degeneration with the", "muscle degeneration with the release", "degeneration with the release of", "with the release of myoglobin", "the release of myoglobin and", "release of myoglobin and creatine", "of myoglobin and creatine kinase", "and creatine kinase merezhinskaya", "creatine kinase merezhinskaya et", "kinase merezhinskaya et al.", "merezhinskaya et al. 2000 .", "et al. 2000 . this", "al. 2000 . this defect", "2000 . this defect could", ". this defect could compromise", "this defect could compromise extreme", "defect could compromise extreme performance", "could compromise extreme performance in", "compromise extreme performance in otherwise", "extreme performance in otherwise healthy", "performance in otherwise healthy individuals.

              slc16a1", "in otherwise healthy individuals.

              slc16a1 is", "otherwise healthy individuals.

              slc16a1 is essential", "healthy individuals.

              slc16a1 is essential for", "individuals.

              slc16a1 is essential for lactate", "is essential for lactate transport", "essential for lactate transport in", "for lactate transport in muscle", "lactate transport in muscle cells.", "transport in muscle cells. it", "in muscle cells. it is", "muscle cells. it is also", "cells. it is also highly", "it is also highly enriched", "is also highly enriched in", "also highly enriched in astrocytes", "highly enriched in astrocytes and", "enriched in astrocytes and oligodendroglia", "astrocytes and oligodendroglia neuroglia", "and oligodendroglia neuroglia that", "oligodendroglia neuroglia that support", "neuroglia that support insulate", "that support insulate and", "support insulate and provide", "insulate and provide energy metabolites", "and provide energy metabolites to", "provide energy metabolites to axons.", "energy metabolites to axons. oligodendroglia", "metabolites to axons. oligodendroglia dysfunction", "to axons. oligodendroglia dysfunction can", "axons. oligodendroglia dysfunction can lead", "oligodendroglia dysfunction can lead to", "dysfunction can lead to axon", "can lead to axon degeneration", "lead to axon degeneration in", "to axon degeneration in several", "axon degeneration in several diseases.", "degeneration in several diseases. the", "in several diseases. the cause", "several diseases. the cause is", "diseases. the cause is unknown", "the cause is unknown but", "cause is unknown but disruption", "is unknown but disruption of", "unknown but disruption of slc16a1", "but disruption of slc16a1 transporter", "disruption of slc16a1 transporter produces", "of slc16a1 transporter produces axon", "slc16a1 transporter produces axon damage", "transporter produces axon damage and", "produces axon damage and neuron", "axon damage and neuron loss", "damage and neuron loss in", "and neuron loss in animal", "neuron loss in animal and", "loss in animal and cell", "in animal and cell culture", "animal and cell culture models.", "and cell culture models. in", "cell culture models. in humans", "models. in humans this", "in humans this transporter", "humans this transporter is", "this transporter is reduced in", "transporter is reduced in patients", "is reduced in patients with", "reduced in patients with amyotrophic", "in patients with amyotrophic lateral", "patients with amyotrophic lateral sclerosis", "amyotrophic lateral sclerosis lee", "lateral sclerosis lee et", "sclerosis lee et al.", "lee et al. 2012 .

              in", "et al. 2012 .

              in cancer", "al. 2012 .

              in cancer cells", ".

              in cancer cells a", "cancer cells a common", "cells a common change", "a common change is the", "common change is the upregulation", "change is the upregulation of", "is the upregulation of glycolysis.", "the upregulation of glycolysis. the", "upregulation of glycolysis. the anti", "of glycolysis. the anti cancer", "glycolysis. the anti cancer drug", "the anti cancer drug candidate", "anti cancer drug candidate 3", "cancer drug candidate 3 bromopyruvate", "candidate 3 bromopyruvate 3", "3 bromopyruvate 3 brpa", "3 brpa can inhibit", "brpa can inhibit glycolysis", "can inhibit glycolysis through its", "inhibit glycolysis through its uptake", "glycolysis through its uptake into", "through its uptake into cancer", "its uptake into cancer cells", "uptake into cancer cells via", "into cancer cells via slc16a1", "cancer cells via slc16a1 so", "cells via slc16a1 so it", "via slc16a1 so it is", "slc16a1 so it is the", "so it is the main", "it is the main determinant", "is the main determinant of", "the main determinant of 3", "main determinant of 3 brpa", "determinant of 3 brpa sensitivity", "of 3 brpa sensitivity in", "3 brpa sensitivity in these", "brpa sensitivity in these cells", "in these cells birsoy", "these cells birsoy et", "cells birsoy et al.", "birsoy et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1734", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619071", "r hsa", "hsa 5619071", "r hsa 5619071" ] }, { "record_id": "GLY_000594_1_1734", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc22a12", "slc22a12 causes", "causes renal", "renal hypouricemia", "hypouricemia 1", "defective slc22a12 causes", "slc22a12 causes renal", "causes renal hypouricemia", "renal hypouricemia 1", "1 rhuc1", "defective slc22a12 causes renal", "slc22a12 causes renal hypouricemia", "causes renal hypouricemia 1", "hypouricemia 1 rhuc1", "defective slc22a12 causes 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high urinary urate", "and high urinary urate excretion", "urinary urate excretion wakida", "urate excretion wakida et", "excretion wakida et al.", "et al. 2005 esparza", "al. 2005 esparza martin", "2005 esparza martin &", "esparza martin & garcia nieto", "martin & garcia nieto 2011", "& garcia nieto 2011 ." ] }, { "record_id": "GLY_000594_1_1735", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619072", "r hsa", "hsa 5619072", "r hsa 5619072" ] }, { "record_id": "GLY_000594_1_1735", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc35a2", "slc35a2 causes", "causes congenital", "congenital disorder", "disorder of", "of glycosylation", "glycosylation 2m", "defective slc35a2 causes", "slc35a2 causes congenital", "causes congenital disorder", "congenital disorder of", "disorder of glycosylation", "of glycosylation 2m", "2m cdg2m", "defective slc35a2 causes congenital", "slc35a2 causes 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slc35a2", "human gene slc35a2 encodes", "gene slc35a2 encodes the", "slc35a2 encodes the udp", "encodes the udp galactose", "the udp galactose transporter.", "udp galactose transporter. it", "galactose transporter. it is", "transporter. it is located", "it is located on", "is located on the", "located on the golgi", "on the golgi membrane", "the golgi membrane and", "golgi membrane and mediates", "membrane and mediates the", "and mediates the antiport", "mediates the antiport of", "the antiport of udp", "antiport of udp gal", "of udp gal into", "udp gal into the", "gal into the golgi", "into the golgi lumen", "the golgi lumen in", "golgi lumen in exchange", "lumen in exchange for", "in exchange for ump.", "exchange for ump. nucleotide", "for ump. nucleotide sugars", "ump. nucleotide sugars such", "nucleotide sugars such as", "sugars such as udp", "such as udp gal", "as udp gal are", "udp gal are used", "gal are used in", "are used in protein", "used in protein glycosylation", "in 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n", "glcnac terminated n glycans", "terminated n glycans and", "n glycans and alpha", "glycans and alpha galnac", "and alpha galnac terminated", "alpha galnac terminated o", "galnac terminated o glycans.", "terminated o glycans. defects", "o glycans. defects in", "glycans. defects in slc35a2", "defects in slc35a2 can", "in slc35a2 can cause", "slc35a2 can cause congenital", "can cause congenital disorder", "cause congenital disorder of", "mim:300896 a", "300896 a", "a disorder characterised by", "disorder characterised by developmental", "characterised by developmental delay", "developmental delay hypotonia", "hypotonia ocular defects", "ocular defects and brain", "defects and brain malformations", "brain malformations ng", "malformations ng et", "ng et al. 2013", "et al. 2013 .", "al. 2013 . congenital", "2013 . congenital disorders", ". congenital disorders of", "congenital disorders of glycosylation", "of glycosylation cdgs", "cdgs are generally", "are generally characterised by", "generally characterised by under", "characterised by under glycosylated", "by under glycosylated serum", "under glycosylated serum glycoproteins", "glycosylated serum glycoproteins and", "serum glycoproteins and a", "glycoproteins and a wide", "and a wide spectrum", "a wide spectrum of", "wide spectrum of clinical", "spectrum of clinical features.", "of clinical features. defects", "clinical features. defects in", "features. defects in slc35a2", "in slc35a2 can also", "slc35a2 can also cause", "can also cause early", "also cause early infantile", "cause early infantile epileptic", "early infantile epileptic encephalopathy", "infantile epileptic encephalopathy 22", "encephalopathy 22 eiee22", "a severe form of", "severe form of epilepsy", "form of epilepsy characterised", "of epilepsy characterised by", "epilepsy characterised by by", "characterised by by frequent", "by by frequent tonic", "by frequent tonic seizures", "frequent tonic seizures or", "tonic seizures or spasms", "seizures or spasms beginning", "or spasms beginning in", "spasms beginning in infancy", "beginning in infancy and", "in infancy and accompanied", "infancy and accompanied by", "and accompanied by developmental", "accompanied by developmental problems", "developmental problems kodera", "problems kodera et", "kodera et al. 2013", "the human gene slc35a2 encodes", "human gene slc35a2 encodes the", "gene slc35a2 encodes the udp", "slc35a2 encodes the udp galactose", "encodes the udp galactose transporter.", "the udp galactose transporter. it", "udp galactose transporter. it is", "galactose transporter. it is located", "transporter. it is located on", "it is located on the", "is located on the golgi", "located on the golgi membrane", "on the golgi membrane and", "the golgi membrane and mediates", "golgi membrane and mediates the", "membrane and mediates the antiport", "and mediates the antiport of", "mediates the antiport of udp", "the antiport of udp gal", "antiport of udp gal into", "of udp gal into the", "udp gal into the golgi", "gal into the golgi lumen", "into the golgi lumen in", "the golgi lumen in exchange", "golgi lumen in exchange for", "lumen in exchange for ump.", "in exchange for ump. nucleotide", "exchange for ump. nucleotide sugars", "for ump. nucleotide sugars such", "ump. nucleotide sugars such as", "nucleotide sugars such as udp", "sugars such as udp gal", "such as udp gal are", "as udp gal are used", "udp gal are used in", "gal are used in protein", "are used in protein glycosylation", "used in protein glycosylation in", "in protein glycosylation in the", "protein glycosylation in the golgi", "glycosylation in the golgi lumen.", "in the golgi lumen. this", "the golgi lumen. this transporter", "golgi lumen. this transporter is", "lumen. this transporter is also", "this transporter is also known", "transporter is also known to", "is also known to transport", "also known to transport udp", "known to transport udp n", "to transport udp n acetylgalactosamine", "udp n acetylgalactosamine udp", "n acetylgalactosamine udp galnac", "udp galnac by the", "galnac by the same", "by the same antiport mechanism.", "the same antiport mechanism. defects", "same antiport mechanism. defects in", "antiport mechanism. defects in slc35a2", "mechanism. defects in slc35a2 limit", "defects in slc35a2 limit golgi", "in slc35a2 limit golgi localised", "slc35a2 limit golgi localised pools", "limit golgi localised pools of", "golgi localised pools of udp", "localised pools of udp gal", "of udp gal resulting", "udp gal resulting in", "gal resulting in truncated", "resulting in truncated beta glcnac", "in truncated beta glcnac terminated", "truncated beta glcnac terminated n", "beta glcnac terminated n glycans", "glcnac terminated n glycans and", "terminated n glycans and alpha", "n glycans and alpha galnac", "glycans and alpha galnac terminated", "and alpha galnac terminated o", "alpha galnac terminated o glycans.", "galnac terminated o glycans. defects", "terminated o glycans. defects in", "o glycans. defects in slc35a2", "glycans. defects in slc35a2 can", "defects in slc35a2 can cause", "in slc35a2 can cause congenital", "slc35a2 can cause congenital disorder", "can cause congenital disorder of", "cause congenital disorder of glycosylation", "2m cdg2m mim:300896", "mim:300896 a disorder", "300896 a disorder", "a disorder characterised by developmental", "disorder characterised by developmental delay", "by developmental delay hypotonia", "delay hypotonia ocular", "hypotonia ocular defects and", "ocular defects and brain malformations", "and brain malformations ng", "brain malformations ng et", "malformations ng et al.", "ng et al. 2013 .", "et al. 2013 . congenital", "al. 2013 . congenital disorders", "2013 . congenital disorders of", ". congenital disorders of glycosylation", "disorders of glycosylation cdgs", "glycosylation cdgs are", "cdgs are generally characterised", "are generally characterised by under", "generally characterised by under glycosylated", "characterised by under glycosylated serum", "by under glycosylated serum glycoproteins", "under glycosylated serum glycoproteins and", "glycosylated serum glycoproteins and a", "serum glycoproteins and a wide", "glycoproteins and a wide spectrum", "and a wide spectrum of", "a wide spectrum of clinical", "wide spectrum of clinical features.", "spectrum of clinical features. defects", "of clinical features. defects in", "clinical features. defects in slc35a2", "features. defects in slc35a2 can", "defects in slc35a2 can also", "in slc35a2 can also cause", "slc35a2 can also cause early", "can also cause early infantile", "also cause early infantile epileptic", "cause early infantile epileptic encephalopathy", "early infantile epileptic encephalopathy 22", "epileptic encephalopathy 22 eiee22", "22 eiee22 mim:300896", "mim:300896 a severe", "300896 a severe", "a severe form of epilepsy", "severe form of epilepsy characterised", "form of epilepsy characterised by", "of epilepsy characterised by by", "epilepsy characterised by by frequent", "characterised by by frequent tonic", "by by frequent tonic seizures", "by frequent tonic seizures or", "frequent tonic seizures or spasms", "tonic seizures or spasms beginning", "seizures or spasms beginning in", "or spasms beginning in infancy", "spasms beginning in infancy and", "beginning in infancy and accompanied", "in infancy and accompanied by", "infancy and accompanied by developmental", "and accompanied by developmental problems", "by developmental problems kodera", "developmental problems kodera et", "problems kodera et al.", "kodera et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1736", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619073", "r hsa", "hsa 5619073", "r hsa 5619073" ] }, { "record_id": "GLY_000594_1_1736", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective gck", "gck causes", "causes 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gck", "cells. defects in gck are", "defects in gck are can", "in gck are can cause", "gck are can cause maturity", "are can cause maturity onset", "can cause maturity onset diabetes", "cause maturity onset diabetes of", "2 mody2 mim:125851", "mim:125851 a heritable", "125851 a heritable", "a heritable early onset form", "heritable early onset form of", "early onset form of type", "onset form of type ii", "form of type ii diabetes", "type ii diabetes hussain", "ii diabetes hussain 2010", "hussain 2010 osbak et", "2010 osbak et al.", "osbak et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1737", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619076", "r hsa", "hsa 5619076", "r hsa 5619076" ] }, { "record_id": "GLY_000594_1_1737", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc17a8", "slc17a8 causes", "causes autosomal", "autosomal dominant", "dominant deafness", "deafness 25", "defective slc17a8 causes", "slc17a8 causes autosomal", "causes autosomal dominant", "autosomal dominant deafness", "dominant deafness 25", "25 dfna25", "defective slc17a8 causes autosomal", "slc17a8 causes autosomal dominant", "causes autosomal dominant deafness", "autosomal dominant deafness 25", "deafness 25 dfna25", "defective slc17a8 causes autosomal dominant", "slc17a8 causes autosomal dominant deafness", "causes autosomal dominant deafness 25", "dominant deafness 25 dfna25", "there are", "are two", "two classes", "classes of", "of glutamate", "glutamate transporters", "the excitatory", "excitatory amino", "amino acid", "acid transporters", "which depend", "depend on", "on an", "an electrochemical", "electrochemical gradient", "gradient of", "of na+", "na+ ions", "ions and", "and vesicular", "vesicular glutamate", "which are", "are proton", "proton dependent.", "dependent. together", "these transporters", "transporters uptake", "uptake and", "and release", "release glutamate", "glutamate to", "to mediate", "mediate this", "this neurotransmitter's", "neurotransmitter's excitatory", "excitatory signal", "signal and", "and are", "are part", "part of", "of the", "the glutamate", "glutamate glutamine", "glutamine cycle.", "cycle. three", "three members", "members of", "the slc17a", "slc17a gene", "gene family", "6 and", "and 8", "encode vgluts", "vgluts 1", "1 3", "3 respectively.", "respectively. this", "this uptake", "uptake is", "is thought", "thought to", "to be", "be coupled", "coupled to", "to the", "the proton", "proton electrochemical", "gradient generated", "generated by", "by the", "the vacuolar", "vacuolar type", "type h+", "h+ atpase.", "atpase. they", "they are", "are all", "all expressed", "expressed in", "in the", "the cns", "cns in", "in neuron", "neuron rich", "rich areas", "areas but", "but slc17a8", "is also", "also expressed", "expressed on", "on astrocytes", "astrocytes and", "and in", "the liver", "liver and", "and kidney.", "kidney. defects", "defects in", "in slc17a8", "slc17a8 can", "can cause", "cause autosomal", "a form", "form of", "of non", "non syndromic", "syndromic sensorineural", "sensorineural hearing", "hearing loss.", "loss. the", "the cochlea", "cochlea expresses", "expresses slc17a8", "slc17a8 and", "in mice", "mice which", "which lack", "lack this", "this transporter", "transporter are", "are congenitally", "congenitally deaf.", "deaf. hearing", "hearing loss", "loss is", "is due", "due to", "the lack", "lack of", "glutamate release", "release by", "by inner", "inner hair", "hair cells", "cells therefore", "therefore a", "a loss", "loss of", "of synaptic", "synaptic transmission", "transmission at", "at the", "the ihc", "ihc afferent", "afferent nerve", "nerve synapse.", "synapse. successful", "successful restoration", "restoration of", "of hearing", "hearing by", "by gene", "gene replacement", "replacement in", "mice could", "could be", "be a", "a significant", "significant advance", "advance toward", "toward gene", "gene therapy", "therapy of", "of human", "human deafness", "ruel et", "et al.", "al. 2008", "akil et", "al. 2012", "2012 .", "there are two", "are two classes", "two classes of", "classes of glutamate", "of glutamate transporters", "transporters the", "the excitatory amino", "excitatory amino acid", "amino acid transporters", "transporters eaats", "eaats which", "which depend on", "depend on an", "on an electrochemical", "an electrochemical gradient", "electrochemical gradient of", "gradient of na+", "of na+ ions", "na+ ions and", "ions and vesicular", "and vesicular glutamate", "vesicular glutamate transporters", "transporters vgluts", "vgluts which", "which are proton", "are proton dependent.", "proton dependent. together", "together these", "these transporters uptake", "transporters uptake and", "uptake and release", "and release glutamate", "release glutamate to", "glutamate to mediate", "to mediate this", "mediate this neurotransmitter's", "this neurotransmitter's excitatory", "neurotransmitter's excitatory signal", "excitatory signal and", "signal and are", "and are part", "are part of", "part of the", "of the glutamate", "the glutamate glutamine", "glutamate glutamine cycle.", "glutamine cycle. three", "cycle. three members", "three members of", "members of the", "of the slc17a", "the slc17a gene", "slc17a gene family", "family 7", "7 6", "6 and 8", "8 encode", "encode vgluts 1", "vgluts 1 3", "1 3 respectively.", "3 respectively. this", "respectively. this uptake", "this uptake is", "uptake is thought", "is thought to", "thought to be", "to be coupled", "be coupled to", "coupled to the", "to the proton", "the proton electrochemical", "proton electrochemical gradient", "electrochemical gradient generated", "gradient generated by", "generated by the", "by the vacuolar", "the vacuolar type", "vacuolar type h+", "type h+ atpase.", "h+ atpase. they", "atpase. they are", "they are all", "are all expressed", "all expressed in", "expressed in the", "in the cns", "the cns in", "cns in neuron", "in neuron rich", "neuron rich areas", "rich areas but", "areas but slc17a8", "slc17a8 vglut3", "vglut3 is", "is also expressed", "also expressed on", "expressed on astrocytes", "on astrocytes and", "astrocytes and in", "and in the", "in the liver", "the liver and", "liver and kidney.", "and kidney. defects", "kidney. defects in", "defects in slc17a8", "in slc17a8 can", "slc17a8 can cause", "can cause autosomal", "cause autosomal dominant", "dfna25 mim:605583", "a form of", "form of non", "of non syndromic", "non syndromic sensorineural", "syndromic sensorineural hearing", "sensorineural hearing loss.", "hearing loss. the", "loss. the cochlea", "the cochlea expresses", "cochlea expresses slc17a8", "expresses slc17a8 and", "slc17a8 and in", "and in mice", "in mice which", "mice which lack", "which lack this", "lack this transporter", "this transporter are", "transporter are congenitally", "are congenitally deaf.", "congenitally deaf. hearing", "deaf. hearing loss", "hearing loss is", "loss is due", "is due to", "due to the", "to the lack", "the lack of", "lack of glutamate", "of glutamate release", "glutamate release by", "release by inner", "by inner hair", "inner hair cells", "hair cells therefore", "cells therefore a", "therefore a loss", "a loss of", "loss of synaptic", "of synaptic transmission", "synaptic transmission at", "transmission at the", "at the ihc", "the ihc afferent", "ihc afferent nerve", "afferent nerve synapse.", "nerve synapse. successful", "synapse. successful restoration", "successful restoration of", "restoration of hearing", "of hearing by", "hearing by gene", "by gene replacement", "gene replacement in", "replacement in mice", "in mice could", "mice could be", "could be a", "be a significant", "a significant advance", "significant advance toward", "advance toward gene", "toward gene therapy", "gene therapy of", "therapy of human", "of human deafness", "deafness ruel", "ruel et al.", "et al. 2008", "2008 akil", "akil et al.", "et al. 2012", "al. 2012 .", "there are two classes", "are two classes of", "two classes of glutamate", "classes of glutamate transporters", "glutamate transporters the", "transporters the excitatory", "the excitatory amino acid", "excitatory amino acid transporters", "acid transporters eaats", "eaats which depend", "which depend on an", "depend on an electrochemical", "on an electrochemical gradient", "an electrochemical gradient of", "electrochemical gradient of na+", "gradient of na+ ions", "of na+ ions and", "na+ ions and vesicular", "ions and vesicular glutamate", "and vesicular glutamate transporters", "glutamate transporters vgluts", "vgluts which are", "which are proton dependent.", "are proton dependent. together", "dependent. together these", "together these transporters", "these transporters uptake and", "transporters uptake and release", "uptake and release glutamate", "and release glutamate to", "release glutamate to mediate", "glutamate to mediate this", "to mediate this neurotransmitter's", "mediate this neurotransmitter's excitatory", "this neurotransmitter's excitatory signal", "neurotransmitter's excitatory signal and", "excitatory signal and are", "signal and are part", "and are part of", "are part of the", "part of the glutamate", "of the glutamate glutamine", "the glutamate glutamine cycle.", "glutamate glutamine cycle. three", "glutamine cycle. three members", "cycle. three members of", "three members of the", "members of the slc17a", "of the slc17a gene", "the slc17a gene family", "gene family 7", "7 6 and", "and 8 encode", "8 encode vgluts", "encode vgluts 1 3", "vgluts 1 3 respectively.", "1 3 respectively. this", "3 respectively. this uptake", "respectively. this uptake is", "this uptake is thought", "uptake is thought to", "is thought to be", "thought to be coupled", "to be coupled to", "be coupled to the", "coupled to the proton", "to the proton electrochemical", "the proton electrochemical gradient", "proton electrochemical gradient generated", "electrochemical gradient generated by", "gradient generated by the", "generated by the vacuolar", "by the vacuolar type", "the vacuolar type h+", "vacuolar type h+ atpase.", "type h+ atpase. they", "h+ atpase. they are", "atpase. they are all", "they are all expressed", "are all expressed in", "all expressed in the", "expressed in the cns", "in the cns in", "the cns in neuron", "cns in neuron rich", "in neuron rich areas", "neuron rich areas but", "rich areas but slc17a8", "but slc17a8 vglut3", "vglut3 is also", "is also expressed on", "also expressed on astrocytes", "expressed on astrocytes and", "on astrocytes and in", "astrocytes and in the", "and in the liver", "in the liver and", "the liver and kidney.", "liver and kidney. defects", "and kidney. defects in", "kidney. defects in slc17a8", "defects in slc17a8 can", "in slc17a8 can cause", "slc17a8 can cause autosomal", "can cause autosomal dominant", "cause autosomal dominant deafness", "mim:605583 a", "605583 a", "a form of non", "form of non syndromic", "of non syndromic sensorineural", "non syndromic sensorineural hearing", "syndromic sensorineural hearing loss.", "sensorineural hearing loss. the", "hearing loss. the cochlea", "loss. the cochlea expresses", "the cochlea expresses slc17a8", "cochlea expresses slc17a8 and", "expresses slc17a8 and in", "slc17a8 and in mice", "and in mice which", "in mice which lack", "mice which lack this", "which lack this transporter", "lack this transporter are", "this transporter are congenitally", "transporter are congenitally deaf.", "are congenitally deaf. hearing", "congenitally deaf. hearing loss", "deaf. hearing loss is", "hearing loss is due", "loss is due to", "is due to the", "due to the lack", "to the lack of", "the lack of glutamate", "lack of glutamate release", "of glutamate release by", "glutamate release by inner", "release by inner hair", "by inner hair cells", "inner hair cells therefore", "hair cells therefore a", "cells therefore a loss", "therefore a loss of", "a loss of synaptic", "loss of synaptic transmission", "of synaptic transmission at", "synaptic transmission at the", "transmission at the ihc", "at the ihc afferent", "the ihc afferent nerve", "ihc afferent nerve synapse.", "afferent nerve synapse. successful", "nerve synapse. successful restoration", "synapse. successful restoration of", "successful restoration of hearing", "restoration of hearing by", "of hearing by gene", "hearing by gene replacement", "by gene replacement in", "gene replacement in mice", "replacement in mice could", "in mice could be", "mice could be a", "could be a significant", "be a significant advance", "a significant advance toward", "significant advance toward gene", "advance toward gene therapy", "toward gene therapy of", "gene therapy of human", "therapy of human deafness", "human deafness ruel", "deafness ruel et", "ruel et al. 2008", "al. 2008 akil", "2008 akil et", "akil et al. 2012", "et al. 2012 .", "there are two classes of", "are two classes of glutamate", "two classes of glutamate transporters", "of glutamate transporters the", "glutamate transporters the excitatory", "transporters the excitatory amino", "the excitatory amino acid transporters", "amino acid transporters eaats", "transporters eaats which", "eaats which depend on", "which depend on an electrochemical", "depend on an electrochemical gradient", "on an electrochemical gradient of", "an electrochemical gradient of na+", "electrochemical gradient of na+ ions", "gradient of na+ ions and", "of na+ ions and vesicular", "na+ ions and vesicular glutamate", "ions and vesicular glutamate transporters", "vesicular glutamate transporters vgluts", "transporters vgluts which", "vgluts which are proton", "which are proton dependent. together", "proton dependent. together these", "dependent. together these transporters", "together these transporters uptake", "these transporters uptake and release", "transporters uptake and release glutamate", "uptake and release glutamate to", "and release glutamate to mediate", "release glutamate to mediate this", "glutamate to mediate this neurotransmitter's", "to mediate this neurotransmitter's excitatory", "mediate this neurotransmitter's excitatory signal", "this neurotransmitter's excitatory signal and", "neurotransmitter's excitatory signal and are", "excitatory signal and are part", "signal and are part of", "and are part of the", "are part of the glutamate", "part of the glutamate glutamine", "of the glutamate glutamine cycle.", "the glutamate glutamine cycle. three", "glutamate glutamine cycle. three members", "glutamine cycle. three members of", "cycle. three members of the", "three members of the slc17a", "members of the slc17a gene", "of the slc17a gene family", "slc17a gene family 7", "family 7 6", "7 6 and 8", "6 and 8 encode", "and 8 encode vgluts", "8 encode vgluts 1", "encode vgluts 1 3 respectively.", "vgluts 1 3 respectively. this", "1 3 respectively. this uptake", "3 respectively. this uptake is", "respectively. this uptake is thought", "this uptake is thought to", "uptake is thought to be", "is thought to be coupled", "thought to be coupled to", "to be coupled to the", "be coupled to the proton", "coupled to the proton electrochemical", "to the proton electrochemical gradient", "the proton electrochemical gradient generated", "proton electrochemical gradient generated by", "electrochemical gradient generated by the", "gradient generated by the vacuolar", "generated by the vacuolar type", "by the vacuolar type h+", "the vacuolar type h+ atpase.", "vacuolar type h+ atpase. they", "type h+ atpase. they are", "h+ atpase. they are all", "atpase. they are all expressed", "they are all expressed in", "are all expressed in the", "all expressed in the cns", "expressed in the cns in", "in the cns in neuron", "the cns in neuron rich", "cns in neuron rich areas", "in neuron rich areas but", "neuron rich areas but slc17a8", "areas but slc17a8 vglut3", "slc17a8 vglut3 is", "vglut3 is also expressed", "is also expressed on astrocytes", "also expressed on astrocytes and", "expressed on astrocytes and in", "on astrocytes and in the", "astrocytes and in the liver", "and in the liver and", "in the liver and kidney.", "the liver and kidney. defects", "liver and kidney. defects in", "and kidney. defects in slc17a8", "kidney. defects in slc17a8 can", "defects in slc17a8 can cause", "in slc17a8 can cause autosomal", "slc17a8 can cause autosomal dominant", "can cause autosomal dominant deafness", "cause autosomal dominant deafness 25", "25 dfna25 mim:605583", "mim:605583 a form", "605583 a form", "a form of non syndromic", "form of non syndromic sensorineural", "of non syndromic sensorineural hearing", "non syndromic sensorineural hearing loss.", "syndromic sensorineural hearing loss. the", "sensorineural hearing loss. the cochlea", "hearing loss. the cochlea expresses", "loss. the cochlea expresses slc17a8", "the cochlea expresses slc17a8 and", "cochlea expresses slc17a8 and in", "expresses slc17a8 and in mice", "slc17a8 and in mice which", "and in mice which lack", "in mice which lack this", "mice which lack this transporter", "which lack this transporter are", "lack this transporter are congenitally", "this transporter are congenitally deaf.", "transporter are congenitally deaf. hearing", "are congenitally deaf. hearing loss", "congenitally deaf. hearing loss is", "deaf. hearing loss is due", "hearing loss is due to", "loss is due to the", "is due to the lack", "due to the lack of", "to the lack of glutamate", "the lack of glutamate release", "lack of glutamate release by", "of glutamate release by inner", "glutamate release by inner hair", "release by inner hair cells", "by inner hair cells therefore", "inner hair cells therefore a", "hair cells therefore a loss", "cells therefore a loss of", "therefore a loss of synaptic", "a loss of synaptic transmission", "loss of synaptic transmission at", "of synaptic transmission at the", "synaptic transmission at the ihc", "transmission at the ihc afferent", "at the ihc afferent nerve", "the ihc afferent nerve synapse.", "ihc afferent nerve synapse. successful", "afferent nerve synapse. successful restoration", "nerve synapse. successful restoration of", "synapse. successful restoration of hearing", "successful restoration of hearing by", "restoration of hearing by gene", "of hearing by gene replacement", "hearing by gene replacement in", "by gene replacement in mice", "gene replacement in mice could", "replacement in mice could be", "in mice could be a", "mice could be a significant", "could be a significant advance", "be a significant advance toward", "a significant advance toward gene", "significant advance toward gene therapy", "advance toward gene therapy of", "toward gene therapy of human", "gene therapy of human deafness", "of human deafness ruel", "human deafness ruel et", "deafness ruel et al.", "et al. 2008 akil", "al. 2008 akil et", "2008 akil et al.", "akil et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1738", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619078", "r hsa", "hsa 5619078", "r hsa 5619078" ] }, { "record_id": "GLY_000594_1_1738", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc35c1", "slc35c1 causes", "causes congenital", "congenital disorder", "disorder of", "of glycosylation", "glycosylation 2c", "defective slc35c1 causes", "slc35c1 causes congenital", "causes congenital disorder", "congenital disorder of", "disorder of glycosylation", "of glycosylation 2c", "2c cdg2c", "defective slc35c1 causes congenital", "slc35c1 causes congenital disorder", "causes congenital disorder of", "congenital disorder of glycosylation", "disorder of glycosylation 2c", "glycosylation 2c cdg2c", "defective slc35c1 causes congenital disorder", "slc35c1 causes congenital disorder of", "causes congenital disorder of glycosylation", "congenital disorder of glycosylation 2c", "of glycosylation 2c cdg2c", "the human", "human gene", "gene slc35c1", "slc35c1 encodes", "encodes a", "a gdp", "gdp fucose", "fucose transporter", "transporter that", "that resides", "resides on", "on the", "the golgi", "golgi membrane", "membrane and", "and mediates", "mediates the", "the transport", "transport of", "of gdp", "fucose into", "into the", "golgi lumen.", "lumen. defects", "defects in", "in slc35c1", "slc35c1 cause", "cause the", "the congenital", "glycosylation type", "type 2c", "cdg2c aka", "aka leukocyte", "leukocyte adhesion", "adhesion deficiency", "deficiency type", "type ii", "an autosomal", "autosomal recessive", "recessive disorder", "disorder characterised", "characterised by", "by moderate", "moderate to", "to severe", "severe psychomotor", "psychomotor retardation", "mild dysmorphism", "dysmorphism and", "and impaired", "impaired neutrophil", "neutrophil motility", "lubke et", "et al.", "al. 2001", "liu &", "& hirschberg", "hirschberg 2013", "2013 .", "the human gene", "human gene slc35c1", "gene slc35c1 encodes", "slc35c1 encodes a", "encodes a gdp", "a gdp fucose", "gdp fucose transporter", "fucose transporter that", "transporter that resides", "that resides on", "resides on the", "on the golgi", "the golgi membrane", "golgi membrane and", "membrane and mediates", "and mediates the", "mediates the transport", "the transport of", "transport of gdp", "of gdp fucose", "gdp fucose into", "fucose into the", "into the golgi", "the golgi lumen.", "golgi lumen. defects", "lumen. defects in", "defects in slc35c1", "in slc35c1 cause", "slc35c1 cause the", "cause the congenital", "the congenital disorder", "of glycosylation type", "glycosylation type 2c", "cdg2c aka leukocyte", "aka leukocyte adhesion", "leukocyte adhesion deficiency", "adhesion deficiency type", "deficiency type ii", "ii lad2", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder characterised", "disorder characterised by", "characterised by moderate", "by moderate to", "moderate to severe", "to severe psychomotor", "severe psychomotor retardation", "retardation mild", "mild dysmorphism and", "dysmorphism and impaired", "and impaired neutrophil", "impaired neutrophil motility", "motility lubke", "lubke et al.", "et al. 2001", "2001 liu", "liu & hirschberg", "& hirschberg 2013", "hirschberg 2013 .", "the human gene slc35c1", "human gene slc35c1 encodes", "gene slc35c1 encodes a", "slc35c1 encodes a gdp", "encodes a gdp fucose", "a gdp fucose transporter", "gdp fucose transporter that", "fucose transporter that resides", "transporter that resides on", "that resides on the", "resides on the golgi", "on the golgi membrane", "the golgi membrane and", "golgi membrane and mediates", "membrane and mediates the", "and mediates the transport", "mediates the transport of", "the transport of gdp", "transport of gdp fucose", "of gdp fucose into", "gdp fucose into the", "fucose into the golgi", "into the golgi lumen.", "the golgi lumen. defects", "golgi lumen. defects in", "lumen. defects in slc35c1", "defects in slc35c1 cause", "in slc35c1 cause the", "slc35c1 cause the congenital", "cause the congenital disorder", "the congenital disorder of", "disorder of glycosylation type", "of glycosylation type 2c", "type 2c cdg2c", "2c cdg2c aka", "cdg2c aka leukocyte adhesion", "aka leukocyte adhesion deficiency", "leukocyte adhesion deficiency type", "adhesion deficiency type ii", "type ii lad2", "lad2 an", "an autosomal recessive disorder", "autosomal recessive disorder characterised", "recessive disorder characterised by", "disorder characterised by moderate", "characterised by moderate to", "by moderate to severe", "moderate to severe psychomotor", "to severe psychomotor retardation", "psychomotor retardation mild", "retardation mild dysmorphism", "mild dysmorphism and impaired", "dysmorphism and impaired neutrophil", "and impaired neutrophil motility", "neutrophil motility lubke", "motility lubke et", "lubke et al. 2001", "al. 2001 liu", "2001 liu &", "liu & hirschberg 2013", "& hirschberg 2013 .", "the human gene slc35c1 encodes", "human gene slc35c1 encodes a", "gene slc35c1 encodes a gdp", "slc35c1 encodes a gdp fucose", "encodes a gdp fucose transporter", "a gdp fucose transporter that", "gdp fucose transporter that resides", "fucose transporter that resides on", "transporter that resides on the", "that resides on the golgi", "resides on the golgi membrane", "on the golgi membrane and", "the golgi membrane and mediates", "golgi membrane and mediates the", "membrane and mediates the transport", "and mediates the transport of", "mediates the transport of gdp", "the transport of gdp fucose", "transport of gdp fucose into", "of gdp fucose into the", "gdp fucose into the golgi", "fucose into the golgi lumen.", "into the golgi lumen. defects", "the golgi lumen. defects in", "golgi lumen. defects in slc35c1", "lumen. defects in slc35c1 cause", "defects in slc35c1 cause the", "in slc35c1 cause the congenital", "slc35c1 cause the congenital disorder", "cause the congenital disorder of", "the congenital disorder of glycosylation", "congenital disorder of glycosylation type", "disorder of glycosylation type 2c", "glycosylation type 2c cdg2c", "type 2c cdg2c aka", "2c cdg2c aka leukocyte", "cdg2c aka leukocyte adhesion deficiency", "aka leukocyte adhesion deficiency type", "leukocyte adhesion deficiency type ii", "deficiency type ii lad2", "lad2 an autosomal", "an autosomal recessive disorder characterised", "autosomal recessive disorder characterised by", "recessive disorder characterised by moderate", "disorder characterised by moderate to", "characterised by moderate to severe", "by moderate to severe psychomotor", "moderate to severe psychomotor retardation", "severe psychomotor retardation mild", "psychomotor retardation mild dysmorphism", "retardation mild dysmorphism and", "mild dysmorphism and impaired neutrophil", "dysmorphism and impaired neutrophil motility", "impaired neutrophil motility lubke", "neutrophil motility lubke et", "motility lubke et al.", "et al. 2001 liu", "al. 2001 liu &", "2001 liu & hirschberg", "liu & hirschberg 2013 ." ] }, { "record_id": "GLY_000594_1_1739", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619079", "r hsa", "hsa 5619079", "r hsa 5619079" ] }, { "record_id": "GLY_000594_1_1739", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc6a18", "slc6a18 may", "may confer", "confer susceptibility", "susceptibility to", "to iminoglycinuria", "iminoglycinuria and/or", "and/or hyperglycinuria", "defective slc6a18 may", "slc6a18 may confer", "may confer susceptibility", "confer susceptibility to", "susceptibility to iminoglycinuria", "to iminoglycinuria and/or", "iminoglycinuria and/or hyperglycinuria", "defective slc6a18 may 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5619092" ] }, { "record_id": "GLY_000594_1_1746", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc9a6", "slc9a6 causes", "x linked", "syndromic mental", "mental retardation", "christianson type", "defective slc9a6 causes", "causes x", "linked syndromic", "syndromic mental retardation", "type mrxsch", "slc9a6 causes x", "causes x linked", "x linked syndromic", "linked syndromic mental", "retardation christianson", "christianson type mrxsch", "defective slc9a6 causes x", "slc9a6 causes x linked", "x linked syndromic mental", "linked syndromic mental retardation", "mental retardation christianson", "retardation christianson type", "slc9a6 encodes", "encodes the", "the sodium/hydrogen", "sodium/hydrogen exchanger", "exchanger 6", "6 nhe6", "a protein", "protein ubiquitously", "ubiquitously expressed", "expressed but", "but most", "most abundant", "abundant in", "in mitochondria", "mitochondria rich", "rich tissues", "tissues such", "such 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of one amino", "uptake of one amino acid", "of one amino acid molecule", "one amino acid molecule is", "amino acid molecule is accompanied", "acid molecule is accompanied by", "molecule is accompanied by uptake", "is accompanied by uptake of", "accompanied by uptake of two", "by uptake of two sodium", "uptake of two sodium ions", "of two sodium ions and", "two sodium ions and a", "sodium ions and a chloride", "ions and a chloride ion", "a chloride ion broer", "chloride ion broer &", "ion broer & gether", "& gether 2012 schweikhard", "gether 2012 schweikhard &", "2012 schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . as", "ziegler 2012 . as assessed", "2012 . as assessed by", ". as assessed by northern", "as assessed by northern blotting", "by northern blotting slc6a14", "northern blotting slc6a14 is", "blotting slc6a14 is expressed", "slc6a14 is expressed at high", "is expressed at high levels", "expressed at high levels in", "at high levels in lung", "high levels in lung but", "levels in lung but only", "in lung but only at", "lung but only at low", "but only at low levels", "at low levels if", "low levels if at", "levels if at all", "if at all in", "at all in intestine", "all in intestine or", "in intestine or kidney. variations", "intestine or kidney. variations in", "or kidney. variations in slc6a14", "kidney. variations in slc6a14 may", "variations in slc6a14 may be", "in slc6a14 may be associated", "slc6a14 may be associated with", "may be associated with obesity", "associated with obesity bmiq11", "obesity bmiq11 mim:300306", "bmiq11 mim:300306 in", "mim:300306 in some populations.", "300306 in some populations.", "in some populations. slc6a14 is", "some populations. slc6a14 is an", "populations. slc6a14 is an interesting", "slc6a14 is an interesting candidate", "is an interesting candidate for", "an interesting candidate for obesity", "interesting candidate for obesity because", "candidate for obesity because it", "for obesity because it may", "obesity because it may potentially", "because it may potentially regulate", "it may potentially regulate tryptophan", "may potentially regulate tryptophan availability", "potentially regulate tryptophan availability for", "regulate tryptophan availability for serotonin", "tryptophan availability for serotonin synthesis", "availability for serotonin synthesis and", "for serotonin synthesis and thus", "serotonin synthesis and thus could", "synthesis and thus could affect", "and thus could affect appetite", "thus could affect appetite control", "affect appetite control suviolahti", "appetite control suviolahti et", "control suviolahti et al.", "et al. 2003 durand", "al. 2003 durand et", "2003 durand et al.", "durand et al. 2004 ." ] }, { "record_id": "GLY_000594_1_1748", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619095", "r hsa", "hsa 5619095", "r hsa 5619095" ] }, { "record_id": "GLY_000594_1_1748", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slco2a1", "slco2a1 causes", "causes primary", "autosomal recessive", "recessive hypertrophic", "hypertrophic osteoarthropathy", "osteoarthropathy 2", "defective slco2a1 causes", "slco2a1 causes primary", "primary autosomal", "autosomal recessive hypertrophic", "recessive hypertrophic osteoarthropathy", "hypertrophic osteoarthropathy 2", "2 phoar2", "defective slco2a1 causes primary", "causes primary autosomal", "primary autosomal recessive", "autosomal recessive hypertrophic osteoarthropathy", "recessive hypertrophic osteoarthropathy 2", "osteoarthropathy 2 phoar2", "slco2a1 causes primary autosomal", "causes primary autosomal recessive", "primary autosomal recessive hypertrophic", "autosomal recessive hypertrophic osteoarthropathy 2", "hypertrophic osteoarthropathy 2 phoar2", "the human", "human gene", "gene slco2a1", "slco2a1 encodes", "encodes prostaglandin", "prostaglandin transporter", "transporter pgt.", "pgt. it", "it is", "is ubiquitously", "ubiquitously expressed", "expressed and", "and can", "can transport", "transport the", "the protaglandins", "protaglandins pgd2", "pge2 and", "and pgf2a.", "pgf2a. this", "this transport", "transport may", "may be", "be important", "important for", "for release", "release of", "of newly", "newly formed", "formed prostaglandins", "and/or their", "their clearance", "clearance of", "of prostaglandins", "prostaglandins from", "from the", "the circulation.", "circulation. defects", "defects in", "in slco2a1", "slco2a1 can", "can cause", "cause hypertrophic", "a rare", "rare genodermatosis", "genodermatosis characterised", "characterised by", "by pachydermia", "digital clubbing", "periostosis and", "and affecting", "affecting more", "more males", "males than", "than females", "castori et", "et al.", "al. 2005", "seifert et", "al. 2012", "diggle et", "madruga dias", "dias et", "al. 2014", "2014 .", "the human gene", "human gene slco2a1", "gene slco2a1 encodes", "slco2a1 encodes prostaglandin", "encodes prostaglandin transporter", "prostaglandin transporter pgt.", "transporter pgt. it", "pgt. it is", "it is ubiquitously", "is ubiquitously expressed", "ubiquitously expressed and", "expressed and can", "and can transport", "can transport the", "transport the protaglandins", "the protaglandins pgd2", "pgd2 pge1", "pge1 pge2", "pge2 and pgf2a.", "and pgf2a. this", "pgf2a. this transport", "this transport may", "transport may be", "may be important", "be important for", "important for release", "for release of", "release of newly", "of newly formed", "newly formed prostaglandins", "prostaglandins pgs", "pgs and/or", "and/or their clearance", "their clearance of", "clearance of prostaglandins", "of prostaglandins from", "prostaglandins from the", "from the circulation.", "the circulation. defects", "circulation. defects in", "defects in slco2a1", "in slco2a1 can", "slco2a1 can cause", "can cause hypertrophic", "cause hypertrophic osteoarthropathy", "osteoarthropathy primary", "recessive 2", "phoar2 mim:614441", "a rare genodermatosis", "rare genodermatosis characterised", "genodermatosis characterised by", "characterised by pachydermia", "pachydermia digital", "clubbing periostosis", "periostosis and affecting", "and affecting more", "affecting more males", "more males than", "males than females", "females castori", "castori et al.", "et al. 2005", "2005 seifert", "seifert et al.", "et al. 2012", "2012 diggle", "diggle et al.", "2012 madruga", "madruga dias et", "dias et al.", "et al. 2014", "al. 2014 .", "the human gene slco2a1", "human gene slco2a1 encodes", "gene slco2a1 encodes prostaglandin", "slco2a1 encodes prostaglandin transporter", "encodes prostaglandin transporter pgt.", "prostaglandin transporter pgt. it", "transporter pgt. it is", "pgt. it is ubiquitously", "it is ubiquitously expressed", "is ubiquitously expressed and", "ubiquitously expressed and can", "expressed and can transport", "and can transport the", "can transport the protaglandins", "transport the protaglandins pgd2", "protaglandins pgd2 pge1", "pge1 pge2 and", "pge2 and pgf2a. this", "and pgf2a. this transport", "pgf2a. this transport may", "this transport may be", "transport may be important", "may be important for", "be important for release", "important for release of", "for release of newly", "release of newly formed", "of newly formed prostaglandins", "formed prostaglandins pgs", "pgs and/or their", "and/or their clearance of", "their clearance of prostaglandins", "clearance of prostaglandins from", "of prostaglandins from the", "prostaglandins from the circulation.", "from the circulation. defects", "the circulation. defects in", "circulation. defects in slco2a1", "defects in slco2a1 can", "in slco2a1 can cause", "slco2a1 can cause hypertrophic", "can cause hypertrophic osteoarthropathy", "hypertrophic osteoarthropathy primary", "autosomal recessive 2", "mim:614441 a", "614441 a", "a rare genodermatosis characterised", "rare genodermatosis characterised by", "genodermatosis characterised by pachydermia", "by pachydermia digital", "pachydermia digital clubbing", "digital clubbing periostosis", "clubbing periostosis and", "periostosis and affecting more", "and affecting more males", "affecting more males than", "more males than females", "than females castori", "females castori et", "castori et al. 2005", "al. 2005 seifert", "2005 seifert et", "seifert et al. 2012", "al. 2012 diggle", "2012 diggle et", "diggle et al. 2012", "al. 2012 madruga", "2012 madruga dias", "madruga dias et al.", "dias et al. 2014", "et al. 2014 .", "the human gene slco2a1 encodes", "human gene slco2a1 encodes prostaglandin", "gene slco2a1 encodes prostaglandin transporter", "slco2a1 encodes prostaglandin transporter pgt.", "encodes prostaglandin transporter pgt. it", "prostaglandin transporter pgt. it is", "transporter pgt. it is ubiquitously", "pgt. it is ubiquitously expressed", "it is 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defects in slco2a1", "circulation. defects in slco2a1 can", "defects in slco2a1 can cause", "in slco2a1 can cause hypertrophic", "slco2a1 can cause hypertrophic osteoarthropathy", "cause hypertrophic osteoarthropathy primary", "osteoarthropathy primary autosomal", "recessive 2 phoar2", "2 phoar2 mim:614441", "mim:614441 a rare", "614441 a rare", "a rare genodermatosis characterised by", "rare genodermatosis characterised by pachydermia", "characterised by pachydermia digital", "by pachydermia digital clubbing", "digital clubbing periostosis and", "clubbing periostosis and affecting", "periostosis and affecting more males", "and affecting more males than", "affecting more males than females", "males than females castori", "than females castori et", "females castori et al.", "et al. 2005 seifert", "al. 2005 seifert et", "2005 seifert et al.", "et al. 2012 diggle", "al. 2012 diggle et", "2012 diggle et al.", "et al. 2012 madruga", "al. 2012 madruga dias", "2012 madruga dias et", "madruga dias et al. 2014", "dias et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1749", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619096", "r hsa", "hsa 5619096", "r hsa 5619096" ] }, { "record_id": "GLY_000594_1_1749", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc5a5", "slc5a5 causes", "causes thyroid", "thyroid dyshormonogenesis", "dyshormonogenesis 1", "defective slc5a5 causes", "slc5a5 causes thyroid", "causes thyroid dyshormonogenesis", "thyroid dyshormonogenesis 1", "1 tdh1", "defective slc5a5 causes thyroid", "slc5a5 causes thyroid dyshormonogenesis", "causes thyroid dyshormonogenesis 1", "dyshormonogenesis 1 tdh1", "defective slc5a5 causes thyroid dyshormonogenesis", "slc5a5 causes thyroid dyshormonogenesis 1", "thyroid dyshormonogenesis 1 tdh1", "human slc5a5", "slc5a5 encodes", "encodes the", "the na+/i", "symporter nis", "nis which", "which is", "is localised", 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slc5a5 encodes", "slc5a5 encodes the", "encodes the na+/i", "na+/i symporter", "symporter nis which", "nis which is", "which is localised", "is localised in", "localised in the", "in the basolateral", "the basolateral membrane", "basolateral membrane of", "membrane of thyrocytes", "of thyrocytes facing", "thyrocytes facing the", "facing the bloodstream", "the bloodstream where", "bloodstream where it", "where it mediates", "it mediates iodide", "mediates iodide accumulation", "iodide accumulation into", "accumulation into these", "into these cells.", "these cells. defects", "cells. defects in", "defects in slc5a5", "in slc5a5 can", "slc5a5 can cause", "can cause hyroid", "cause hyroid dyshormonogenesis", "hyroid dyshormonogenesis 1", "tdh1 mim:274400", "a disorder characterised", "disorder characterised by", "characterised by the", "by the inability", "the inability of", "inability of the", "of the thyroid", "the thyroid to", "thyroid to maintain", "to maintain a", "maintain a 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bloodstream", "facing the bloodstream where", "the bloodstream where it", "bloodstream where it mediates", "where it mediates iodide", "it mediates iodide accumulation", "mediates iodide accumulation into", "iodide accumulation into these", "accumulation into these cells.", "into these cells. defects", "these cells. defects in", "cells. defects in slc5a5", "defects in slc5a5 can", "in slc5a5 can cause", "slc5a5 can cause hyroid", "can cause hyroid dyshormonogenesis", "cause hyroid dyshormonogenesis 1", "mim:274400 a", "274400 a", "a disorder characterised by", "disorder characterised by the", "characterised by the inability", "by the inability of", "the inability of the", "inability of the thyroid", "of the thyroid to", "the thyroid to maintain", "thyroid to maintain a", "to maintain a concentration", "maintain a concentration difference", "a concentration difference of", "concentration difference of readily", "difference of readily exchangeable", "of readily exchangeable iodine", "readily exchangeable iodine between", "exchangeable iodine between the", "iodine between the plasma", "between the plasma and", "the plasma and the", "plasma and the thyroid", "and the thyroid gland", "thyroid gland termed", "gland termed iodine", "iodine trapping leading", "trapping leading to", "leading to congenital hypothyroidism", "congenital hypothyroidism spitzweg", "hypothyroidism spitzweg &", "spitzweg & morris 2010", "morris 2010 grasberger", "2010 grasberger &", "grasberger & refetoff 2011", "& refetoff 2011 .", "human slc5a5 encodes the na+/i", "encodes the na+/i symporter", "the na+/i symporter nis", "na+/i symporter nis which", "symporter nis which is localised", "nis which is localised in", "which is localised in the", "is localised in the basolateral", "localised in the basolateral membrane", "in the basolateral membrane of", "the basolateral membrane of thyrocytes", "basolateral membrane of thyrocytes facing", "membrane of thyrocytes facing the", "of thyrocytes facing the bloodstream", "thyrocytes facing the bloodstream where", "facing the bloodstream where it", "the bloodstream where it mediates", "bloodstream where it mediates iodide", "where it mediates iodide accumulation", "it mediates iodide accumulation into", "mediates iodide accumulation into these", "iodide accumulation into these cells.", "accumulation into these cells. defects", "into these cells. defects in", "these cells. defects in slc5a5", "cells. defects in slc5a5 can", "defects in slc5a5 can cause", "in slc5a5 can cause hyroid", "slc5a5 can cause hyroid dyshormonogenesis", "can cause hyroid dyshormonogenesis 1", "hyroid dyshormonogenesis 1 tdh1", "1 tdh1 mim:274400", "mim:274400 a disorder", "274400 a disorder", "a disorder characterised by the", "disorder characterised by the inability", "characterised by the inability of", "by the inability of the", "the inability of the thyroid", "inability of the thyroid to", "of the thyroid to maintain", "the thyroid to maintain a", "thyroid to maintain a concentration", "to maintain a concentration difference", "maintain a concentration difference of", "a concentration difference of readily", "concentration difference of readily exchangeable", "difference of readily exchangeable iodine", "of readily exchangeable iodine between", "readily exchangeable iodine between the", "exchangeable iodine between the plasma", "iodine between the plasma and", "between the plasma and the", "the plasma and the thyroid", "plasma and the thyroid gland", "the thyroid gland termed", "thyroid gland termed iodine", "gland termed iodine trapping", "termed iodine trapping leading", "iodine trapping leading to", "trapping leading to congenital", "to congenital hypothyroidism spitzweg", "congenital hypothyroidism spitzweg &", "hypothyroidism spitzweg & morris", "& morris 2010 grasberger", "morris 2010 grasberger &", "2010 grasberger & refetoff", "grasberger & refetoff 2011 ." ] }, { "record_id": "GLY_000594_1_1750", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619097", "r hsa", "hsa 5619097", "r hsa 5619097" ] }, { "record_id": "GLY_000594_1_1750", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc34a3", "slc34a3 causes", "causes hereditary", "hereditary hypophosphatemic", "hypophosphatemic rickets", "rickets with", "with hypercalciuria", "defective slc34a3 causes", "slc34a3 causes hereditary", "causes hereditary hypophosphatemic", "hereditary hypophosphatemic rickets", "hypophosphatemic rickets with", "rickets with hypercalciuria", "hypercalciuria hhrh", "defective slc34a3 causes hereditary", "slc34a3 causes hereditary hypophosphatemic", "causes hereditary hypophosphatemic rickets", "hereditary hypophosphatemic rickets with", "hypophosphatemic rickets with hypercalciuria", "with hypercalciuria hhrh", "defective slc34a3 causes hereditary hypophosphatemic", "slc34a3 causes hereditary hypophosphatemic rickets", "causes hereditary hypophosphatemic rickets with", "hereditary hypophosphatemic rickets with hypercalciuria", "rickets with hypercalciuria hhrh", "slc34a3 is", "is almost", "almost exclusively", "exclusively expressed", "expressed at", "at the", "the apical", "apical membranes", "membranes of", "of kidney", "kidney proximal", "proximal tubules", "tubules and", "and encodes", "encodes a", "a na+/pi", "na+/pi cotransporter.", "cotransporter. it", "it cotransports", "cotransports 2", "2 na+", "na+ ions", "ions with", "with every", "every phosphate", "electroneutral transport", "transport .", ". defects", "defects in", "in slc34a3", "slc34a3 are", "are the", "the cause", "cause of", "of hereditary", "an autosomal", "autosomal recessive", "recessive form", "form of", "of hypophosphatemia", "hypophosphatemia characterised", "characterised by", "by reduced", "reduced renal", "renal phosphate", "phosphate reabsorption", "reabsorption and", "and rickets", "bergwitz et", "et al.", "al. 2006", "segawa et", "al. 2013", "forster et", "2013 .", "slc34a3 is almost", "is almost exclusively", "almost exclusively expressed", "exclusively expressed at", "expressed at the", "at the apical", "the apical membranes", "apical membranes of", "membranes of kidney", "of kidney proximal", "kidney proximal tubules", "proximal tubules and", "tubules and encodes", "and encodes a", "encodes a na+/pi", "a na+/pi cotransporter.", "na+/pi cotransporter. it", "cotransporter. it cotransports", "it cotransports 2", "cotransports 2 na+", "2 na+ ions", "na+ ions with", "ions with every", "with every phosphate", "phosphate pi", "electroneutral transport .", "transport . defects", ". defects in", "defects in slc34a3", "in slc34a3 are", "slc34a3 are the", "are the cause", "the cause of", "cause of hereditary", "of hereditary hypophosphatemic", "hhrh mim:241530", "an autosomal recessive", "autosomal recessive form", "recessive form of", "form of hypophosphatemia", "of hypophosphatemia characterised", "hypophosphatemia characterised by", "characterised by reduced", "by reduced renal", "reduced renal phosphate", "renal phosphate reabsorption", "phosphate reabsorption and", "reabsorption and rickets", "rickets bergwitz", "bergwitz et al.", "et al. 2006", "2006 segawa", "segawa et al.", "et al. 2013", "2013 forster", "forster et al.", "al. 2013 .", "slc34a3 is almost exclusively", "is almost exclusively expressed", "almost exclusively expressed at", "exclusively expressed at the", "expressed at the apical", "at the apical membranes", "the apical membranes of", "apical membranes of kidney", "membranes of kidney proximal", "of kidney proximal tubules", "kidney proximal tubules and", "proximal tubules and encodes", "tubules and encodes a", "and encodes a na+/pi", "encodes a na+/pi cotransporter.", "a na+/pi cotransporter. it", "na+/pi cotransporter. it cotransports", "cotransporter. it cotransports 2", "it cotransports 2 na+", "cotransports 2 na+ ions", "2 na+ ions with", "na+ ions with 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"forster et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1751", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619101", "r hsa", "hsa 5619101", "r hsa 5619101" ] }, { "record_id": "GLY_000594_1_1751", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "variant slc6a20", "slc6a20 contributes", "contributes towards", "towards hyperglycinuria", "and iminoglycinuria", "variant slc6a20 contributes", "slc6a20 contributes towards", "contributes towards hyperglycinuria", "hyperglycinuria hg", "hg and", "iminoglycinuria ig", "variant slc6a20 contributes towards", "slc6a20 contributes towards hyperglycinuria", "towards hyperglycinuria hg", "hg and iminoglycinuria", "and iminoglycinuria ig", "variant slc6a20 contributes towards hyperglycinuria", "contributes towards hyperglycinuria hg", "hyperglycinuria hg and", "slc6a20 encodes", "encodes the", "the sodium", "and chloride", "chloride dependent", 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clinical features present in", "clinical features present in infancy", "features present in infancy and", "present in infancy and include", "in infancy and include muscle", "infancy and include muscle weakness", "include muscle weakness anorexia", "weakness anorexia polydipsia", "anorexia polydipsia polyuria", "polydipsia polyuria failure", "polyuria failure to thrive", "failure to thrive and mental", "to thrive and mental and", "thrive and mental and growth", "and mental and growth retardation", "and growth retardation favero", "growth retardation favero et", "retardation favero et al.", "et al. 2011 gagnon", "al. 2011 gagnon &", "2011 gagnon & delpire", "gagnon & delpire 2013 ." ] }, { "record_id": "GLY_000594_1_1753", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619108", "r hsa", "hsa 5619108", "r hsa 5619108" ] }, { "record_id": "GLY_000594_1_1753", "filename": "human_protein_pathways_reactome", "fieldtype": "text", 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expressed", "is also expressed at", "also expressed at lower", "expressed at lower levels", "at lower levels in", "lower levels in brain", "in brain kidney", "kidney liver and", "liver and heart. slc27a4", "and heart. slc27a4 is", "heart. slc27a4 is also", "slc27a4 is also expressed", "is also expressed in", "also expressed in skin", "in skin where", "skin where it", "where it has been", "it has been shown", "has been shown to", "been shown to play", "shown to play a", "to play a major", "play a major role", "a major role in", "major role in epidermal", "role in epidermal development", "epidermal development being", "development being highly", "being highly expressed in", "highly expressed in neonatal", "expressed in neonatal keratinocytes.", "in neonatal keratinocytes. defects", "neonatal keratinocytes. defects in", "keratinocytes. defects in slc27a4", "defects in slc27a4 can", "in slc27a4 can cause", "slc27a4 can cause ichthyosis", "can cause ichthyosis prematurity", "cause ichthyosis prematurity syndrome", "mim:604194 a", "604194 a", "a keratinisation disorder which", "keratinisation disorder which is", "disorder which is characterised", "which is characterised by", "is characterised by thickened", "characterised by thickened epidermis", "by thickened epidermis and", "thickened epidermis and respiratory", "epidermis and respiratory complications.", "and respiratory complications. patients", "respiratory complications. patients suffer", "complications. patients suffer from", "patients suffer from a", "suffer from a lifelong", "from a lifelong non", "a lifelong non scaly", "lifelong non scaly ichthyosis", "scaly ichthyosis anderson", "ichthyosis anderson &", "anderson & stahl 2013", "& stahl 2013 .", "the slc27 gene family code", "slc27 gene family code for", "gene family code for fatty", "family code for fatty acid", "code for fatty acid transport", "for fatty acid transport proteins", "acid transport proteins fatps", "transport proteins fatps .", "proteins fatps . long", "fatps . long chain fatty", ". long chain fatty acids", "chain fatty acids lcfas", "acids lcfas are", "lcfas are critical for", "are critical for many physiological", "critical for many physiological and", "for many physiological and cellular", "many physiological and cellular processes", "physiological and cellular processes as", "and cellular processes as a", "cellular processes as a primary", "processes as a primary energy", "as a primary energy source.", "a primary energy source. of", "primary energy source. of the", "energy source. of the six", "source. of the six fatps", "of the six fatps characterised", "six fatps characterised three", "fatps characterised three have", "characterised three have been", "three have been shown to", "have been shown to mediate", "been shown to mediate the", "shown to mediate the influx", "to mediate the influx of", "mediate the influx of lcfas", "the influx of lcfas into", "influx of lcfas into cells", "lcfas into cells fatp1", "cells fatp1 4", "fatp1 4 and 6.", "and 6. slc27a4 fatp4", "slc27a4 fatp4 is", "fatp4 is the major", "is the major intestinal lcfa", "the major intestinal lcfa transporter", "major intestinal lcfa transporter but", "intestinal lcfa transporter but is", "lcfa transporter but is also", "transporter but is also expressed", "but is also expressed at", "is also expressed at lower", "also expressed at lower levels", "expressed at lower levels in", "at lower levels in brain", "levels in brain kidney", "brain kidney liver", "kidney liver and heart.", "liver and heart. slc27a4 is", "and heart. slc27a4 is also", "heart. slc27a4 is also expressed", "slc27a4 is also expressed in", "is also expressed in skin", "expressed in skin where", "in skin where it", "skin where it has", "where it has been shown", "it has been shown to", "has been shown to play", "been shown to play a", "shown to play a major", "to play a major role", "play a major role in", "a major role in epidermal", "major role in epidermal development", "in epidermal development being", "epidermal development being highly", "development being highly expressed", "being highly expressed in neonatal", "highly expressed in neonatal keratinocytes.", "expressed in neonatal keratinocytes. defects", "in neonatal keratinocytes. defects in", "neonatal keratinocytes. defects in slc27a4", "keratinocytes. defects in slc27a4 can", "defects in slc27a4 can cause", "in slc27a4 can cause ichthyosis", "slc27a4 can cause ichthyosis prematurity", "can cause ichthyosis prematurity syndrome", "syndrome ips mim:604194", "mim:604194 a keratinisation", "604194 a keratinisation", "a keratinisation disorder which is", "keratinisation disorder which is characterised", "disorder which is characterised by", "which is characterised by thickened", "is characterised by thickened epidermis", "characterised by thickened epidermis and", "by thickened epidermis and respiratory", "thickened epidermis and respiratory complications.", "epidermis and respiratory complications. patients", "and respiratory complications. patients suffer", "respiratory complications. patients suffer from", "complications. patients suffer from a", "patients suffer from a lifelong", "suffer from a lifelong non", "from a lifelong non scaly", "a lifelong non scaly ichthyosis", "non scaly ichthyosis anderson", "scaly ichthyosis anderson &", "ichthyosis anderson & stahl", "anderson & stahl 2013 ." ] }, { "record_id": "GLY_000594_1_1754", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619111", "r hsa", "hsa 5619111", "r hsa 5619111" ] }, { "record_id": "GLY_000594_1_1754", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc20a2", "slc20a2 causes", "causes idiopathic", "idiopathic basal", "basal ganglia", "ganglia calcification", "calcification 1", "defective slc20a2 causes", "slc20a2 causes idiopathic", "causes idiopathic basal", "idiopathic basal ganglia", "basal ganglia calcification", "ganglia calcification 1", "1 ibgc1", "defective slc20a2 causes idiopathic", "slc20a2 causes idiopathic basal", "causes idiopathic basal ganglia", "idiopathic basal ganglia calcification", "basal ganglia calcification 1", "calcification 1 ibgc1", "defective slc20a2 causes idiopathic basal", "slc20a2 causes idiopathic basal ganglia", "causes idiopathic basal ganglia calcification", "idiopathic basal ganglia calcification 1", "ganglia calcification 1 ibgc1", "the genes", "genes slc20a1", "slc20a1 and", "and slc20a2", "slc20a2 encode", "encode for", "for phosphate", "phosphate transporters", "transporters 1", "1 and", "and 2", "pit1 and", "and pit2", "pit2 respectively", "respectively .", ". they", "they both", "both have", "have a", "a broad", "broad tissue", "tissue distribution", "distribution and", "and may", "may play", "play a", "a general", "general housekeeping", "housekeeping role", "role in", "in phosphate", "phosphate transport", "transport such", "such as", "as absorbing", "absorbing phosphate", "phosphate from", "from interstitial", "interstitial fluid", "fluid and", "and in", "in extracellular", "extracellular matrix", "matrix and", "and cartilage", "cartilage calcification", "calcification as", "as well", "well as", "as in", "in vascular", "vascular calcification.", "calcification.
              they", "
              they possess", "possess na+", "na+ coupled", "coupled phosphate", "cotransporter function", "function with", "with a", "a stoichiometry", "stoichiometry of", "of 2:1", "na+:pi .", ". defects", "defects in", "in slc20a2", "slc20a2 can", "can cause", "cause idiopathic", "an autosomal", "autosomal dominant", "dominant disorder", "disorder characterised", "characterised by", "by vascular", "vascular and", "and pericapillary", "pericapillary calcification", "calcification by", "by calcium", "calcium phosphate", "phosphate in", "in the", "the basal", "ganglia and", "and other", "other brain", "brain regions.", "regions. affected", "affected individuals", "individuals can", "can either", "either be", "be asymptomatic", "asymptomatic or", "or show", "show a", "a wide", "wide spectrum", "spectrum of", "of neuropsychiatric", "neuropsychiatric symptoms", "symptoms including", "including parkinsonism", "parkinsonism and", "and dementia", "wang et", "et al.", "al. 2012", "hsu et", "al. 2013", "ashtari et", "forster et", "2013 .", "the genes slc20a1", "genes slc20a1 and", "slc20a1 and slc20a2", "and slc20a2 encode", "slc20a2 encode for", "encode for phosphate", "for phosphate transporters", "phosphate transporters 1", "transporters 1 and", "1 and 2", "2 pit1", "pit1 and pit2", "and pit2 respectively", "pit2 respectively .", "respectively . they", ". they both", "they both have", "both have a", "have a broad", "a broad tissue", "broad tissue distribution", "tissue distribution and", "distribution and may", "and may play", "may play a", "play a general", "a general housekeeping", "general housekeeping role", "housekeeping role in", "role in phosphate", "in phosphate transport", "phosphate transport such", "transport such as", "such as absorbing", "as absorbing phosphate", "absorbing phosphate from", "phosphate from interstitial", "from interstitial fluid", "interstitial fluid and", "fluid and in", "and in extracellular", "in extracellular matrix", "extracellular matrix and", "matrix and cartilage", "and cartilage calcification", "cartilage calcification as", "calcification as well", "as well as", "well as in", "as in vascular", "in vascular calcification.", "vascular calcification.
              they", "calcification.
              they possess", "
              they possess na+", "possess na+ coupled", "na+ coupled phosphate", "phosphate pi", "pi cotransporter", "cotransporter function with", "function with a", "with a stoichiometry", "a stoichiometry of", "stoichiometry of 2:1", "2:1 na+:pi", "na+:pi . defects", ". defects in", "defects in slc20a2", "in slc20a2 can", "slc20a2 can cause", "can cause idiopathic", "cause idiopathic basal", "ibgc1 mim:213600", "an autosomal dominant", "autosomal dominant disorder", "dominant disorder characterised", "disorder characterised by", "characterised by vascular", "by vascular and", "vascular and pericapillary", "and pericapillary calcification", "pericapillary calcification by", "calcification by calcium", "by calcium phosphate", "calcium phosphate in", "phosphate in the", "in the basal", "the basal ganglia", "basal ganglia and", "ganglia and other", "and other brain", "other brain regions.", "brain regions. affected", "regions. affected individuals", "affected individuals can", "individuals can either", "can either be", "either be asymptomatic", "be asymptomatic or", "asymptomatic or show", "or show a", "show a wide", "a wide spectrum", "wide spectrum of", "spectrum of neuropsychiatric", "of neuropsychiatric symptoms", "neuropsychiatric symptoms including", "symptoms including parkinsonism", "including parkinsonism and", "parkinsonism and dementia", "dementia wang", "wang et al.", "et al. 2012", "2012 hsu", "hsu et al.", "et al. 2013", "2013 ashtari", "ashtari et al.", "2013 forster", "forster et al.", "al. 2013 .", "the genes slc20a1 and", "genes slc20a1 and slc20a2", "slc20a1 and slc20a2 encode", "and slc20a2 encode for", "slc20a2 encode for phosphate", "encode for phosphate transporters", "for phosphate transporters 1", "phosphate transporters 1 and", "transporters 1 and 2", "and 2 pit1", "2 pit1 and", "pit1 and pit2 respectively", "and pit2 respectively .", "pit2 respectively . they", "respectively . they both", ". they both have", "they both have a", "both have a broad", "have a broad tissue", "a broad tissue distribution", "broad tissue distribution and", "tissue distribution and may", "distribution and may play", "and may play a", "may play a general", "play a general housekeeping", "a general housekeeping role", "general housekeeping role in", "housekeeping role in phosphate", "role in phosphate transport", "in phosphate transport such", "phosphate transport such as", "transport such as absorbing", "such as absorbing phosphate", "as absorbing phosphate from", "absorbing phosphate from interstitial", "phosphate from interstitial fluid", "from interstitial fluid and", "interstitial fluid and in", "fluid and in extracellular", "and in extracellular matrix", "in extracellular matrix and", "extracellular matrix and cartilage", "matrix and cartilage calcification", "and cartilage calcification as", "cartilage calcification as well", "calcification as well as", "as well as in", "well as in vascular", "as in vascular calcification.", "in vascular calcification.
              they", "vascular calcification.
              they possess", "calcification.
              they possess na+", "
              they possess na+ coupled", "possess na+ coupled phosphate", "coupled phosphate pi", "pi cotransporter function", "cotransporter function with a", "function with a stoichiometry", "with a stoichiometry of", "a stoichiometry of 2:1", "of 2:1 na+:pi", "2:1 na+:pi .", "na+:pi . defects in", ". defects in slc20a2", "defects in slc20a2 can", "in slc20a2 can cause", "slc20a2 can cause idiopathic", "can cause idiopathic basal", "cause idiopathic basal ganglia", "mim:213600 an", "213600 an", "an autosomal dominant disorder", "autosomal dominant disorder characterised", "dominant disorder characterised by", "disorder characterised by vascular", "characterised by vascular and", "by vascular and pericapillary", "vascular and pericapillary calcification", "and pericapillary calcification by", "pericapillary calcification by calcium", "calcification by calcium phosphate", "by calcium phosphate in", "calcium phosphate in the", "phosphate in the basal", "in the basal ganglia", "the basal ganglia and", "basal ganglia and other", "ganglia and other brain", "and other brain regions.", "other brain regions. affected", "brain regions. affected individuals", "regions. affected individuals can", "affected individuals can either", "individuals can either be", "can either be asymptomatic", "either be asymptomatic or", "be asymptomatic or show", "asymptomatic or show a", "or show a wide", "show a wide spectrum", "a wide spectrum of", "wide spectrum of neuropsychiatric", "spectrum of neuropsychiatric symptoms", "of neuropsychiatric symptoms including", "neuropsychiatric symptoms including parkinsonism", "symptoms including parkinsonism and", "including parkinsonism and dementia", "and dementia wang", "dementia wang et", "wang et al. 2012", "al. 2012 hsu", "2012 hsu et", "hsu et al. 2013", "al. 2013 ashtari", "2013 ashtari et", "ashtari et al. 2013", "al. 2013 forster", "2013 forster et", "forster et al. 2013", "et al. 2013 .", "the genes slc20a1 and slc20a2", "genes slc20a1 and slc20a2 encode", "slc20a1 and slc20a2 encode for", "and slc20a2 encode for phosphate", "slc20a2 encode for phosphate transporters", "encode for phosphate transporters 1", "for phosphate transporters 1 and", "phosphate transporters 1 and 2", "1 and 2 pit1", "and 2 pit1 and", "2 pit1 and pit2", "pit1 and pit2 respectively .", "and pit2 respectively . they", "pit2 respectively . they both", "respectively . they both have", ". they both have a", "they both have a broad", "both have a broad tissue", "have a broad tissue distribution", "a broad tissue distribution and", "broad tissue distribution and may", "tissue distribution and may play", "distribution and may play a", "and may play a general", "may play a general housekeeping", "play a general housekeeping role", "a general housekeeping role in", "general housekeeping role in phosphate", "housekeeping role in phosphate transport", "role in phosphate transport such", "in phosphate transport such as", "phosphate transport such as absorbing", "transport such as absorbing phosphate", "such as absorbing phosphate from", "as absorbing phosphate from interstitial", "absorbing phosphate from interstitial fluid", "phosphate from interstitial fluid and", "from interstitial fluid and in", "interstitial fluid and in extracellular", "fluid and in extracellular matrix", "and in extracellular matrix and", "in extracellular matrix and cartilage", "extracellular matrix and cartilage calcification", "matrix and cartilage calcification as", "and cartilage calcification as well", "cartilage calcification as well as", "calcification as well as in", "as well as in vascular", "well as in vascular calcification.", "as in vascular calcification.
              they", "in vascular calcification.
              they possess", "vascular calcification.
              they possess na+", "calcification.
              they possess na+ coupled", "
              they possess na+ coupled phosphate", "na+ coupled phosphate pi", "phosphate pi cotransporter", "pi cotransporter function with", "cotransporter function with a stoichiometry", "function with a stoichiometry of", "with a stoichiometry of 2:1", "stoichiometry of 2:1 na+:pi", "of 2:1 na+:pi .", "2:1 na+:pi . defects", "na+:pi . defects in slc20a2", ". defects in slc20a2 can", "defects in slc20a2 can cause", "in slc20a2 can cause idiopathic", "slc20a2 can cause idiopathic basal", "can cause idiopathic basal ganglia", "cause idiopathic basal ganglia calcification", "1 ibgc1 mim:213600", "mim:213600 an autosomal", "213600 an autosomal", "an autosomal dominant disorder characterised", "autosomal dominant disorder characterised by", "dominant disorder characterised by vascular", "disorder characterised by vascular and", "characterised by vascular and pericapillary", "by vascular and pericapillary calcification", "vascular and pericapillary calcification by", "and pericapillary calcification by calcium", "pericapillary calcification by calcium phosphate", "calcification by calcium phosphate in", "by calcium phosphate in the", "calcium phosphate in the basal", "phosphate in the basal ganglia", "in the basal ganglia and", "the basal ganglia and other", "basal ganglia and other brain", "ganglia and other brain regions.", "and other brain regions. affected", "other brain regions. affected individuals", "brain regions. affected individuals can", "regions. affected individuals can either", "affected individuals can either be", "individuals can either be asymptomatic", "can either be asymptomatic or", "either be asymptomatic or show", "be asymptomatic or show a", "asymptomatic or show a wide", "or show a wide spectrum", "show a wide spectrum of", "a wide spectrum of neuropsychiatric", "wide spectrum of neuropsychiatric symptoms", "spectrum of neuropsychiatric symptoms including", "of neuropsychiatric symptoms including parkinsonism", "neuropsychiatric symptoms including parkinsonism and", "symptoms including parkinsonism and dementia", "parkinsonism and dementia wang", "and dementia wang et", "dementia wang et al.", "et al. 2012 hsu", "al. 2012 hsu et", "2012 hsu et al.", "et al. 2013 ashtari", "al. 2013 ashtari et", "2013 ashtari et al.", "et al. 2013 forster", "al. 2013 forster et", "2013 forster et al.", "forster et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1755", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5619113", "r hsa", "hsa 5619113", "r hsa 5619113" ] }, { "record_id": "GLY_000594_1_1755", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc3a1", "slc3a1 causes", "causes cystinuria", "defective slc3a1 causes", "slc3a1 causes cystinuria", "cystinuria csnu", "defective slc3a1 causes cystinuria", "causes cystinuria csnu", "slc3a1 causes cystinuria csnu", "neutral and", "and basic", "basic amino", "amino acid", "acid transport", "transport protein", "protein rbat", "and b", "b 0", "0 +", "type amino", "acid transporter", "transporter 1", "are linked", "linked by", "by a", "a disulfide", "disulfide bridge", "bridge to", "to form", "form system", "system b", "like activity", "activity in", "in the", "the high", "high affinity", "affinity transport", "transport of", "of neutral", "and dibasic", "dibasic amino", "amino acids", "acids and", "and cystine.", "cystine. the", "the slc7a9:slc3a1", "slc7a9:slc3a1 heterodimer", "heterodimer mediates", "mediates the", "the electrogenic", "electrogenic exchange", "exchange of", "of extracellular", "extracellular amino", "acids such", "such as", "as l", "l arginine", "l arg", "and l", "l lysine", "l lys", "and cystine", "the oxidised", "oxidised form", "form of", "of l", "l cysteine", "for intracellular", "intracellular neutral", "neutral amino", "l leucine", "l leu", "leu .", ". these", "these solute", "solute carriers", "carriers are", "are mainly", "mainly expressed", "expressed in", "the kidney", "kidney and", "and small", "small intestine", "intestine where", "where they", "they remove", "remove dibasic", "cystine from", "from the", "the renal", "renal tubular", "tubular and", "and intestinal", "intestinal lumen", "lumen respectively", "schweikhard &", "& ziegler", "ziegler 2012", "2012 .", ". defects", "defects in", "in slc3a1", "or slc7a9", "can cause", "cause cystinuria", "an autosomal", "autosomal recessive", "recessive disorder", "disorder characterised", "characterised by", "by impaired", "impaired epithelial", "epithelial cell", "cell transport", "of cystine", "cystine and", "acids in", "the proximal", "proximal renal", "renal tubule", "tubule and", "and gi", "gi tract.", "tract. the", "the build", "build up", "up and", "and low", "low solubility", "solubility of", "cystine causes", "causes the", "the formation", "formation of", "of calculi", "calculi in", "the urinary", "urinary tract", "resulting in", "in obstructive", "obstructive uropathy", "pyelonephritis and", "and in", "in severe", "severe cases", "renal failure", "palacin et", "et al.", "al. 2001", "mattoo &", "& goldfarb", "goldfarb 2008", "fotiadis et", "al. 2013", "saravakos et", "al. 2014", "2014 .", ". cystinuria", "cystinuria is", "is subcategorized", "subcategorized as", "as type", "type a", "mutations on", "on slc3a1", "and type", "type b", "on slc7a9", "slc7a9 .", "neutral and basic", "and basic amino", "basic amino acid", "amino acid transport", "acid transport protein", "transport protein rbat", "rbat slc3a1", "slc3a1 and", "and b 0", "b 0 +", "+ type", "type amino acid", "amino acid transporter", "acid transporter 1", "1 slc7a9", "slc7a9 are", "are linked by", "linked by a", "by a disulfide", "a disulfide bridge", "disulfide bridge to", "bridge to form", "to form system", "form system b", "system b 0", "+ like", "like activity in", "activity in the", "in the high", "the high affinity", "high affinity transport", "affinity transport of", "transport of neutral", "of neutral and", "neutral and dibasic", "and dibasic amino", "dibasic amino acids", "amino acids and", "acids and cystine.", "and cystine. the", "cystine. the slc7a9:slc3a1", "the slc7a9:slc3a1 heterodimer", "slc7a9:slc3a1 heterodimer mediates", "heterodimer mediates the", "mediates the electrogenic", "the electrogenic exchange", "electrogenic exchange of", "exchange of extracellular", "of extracellular amino", "extracellular amino acids", "amino acids such", "acids such as", "such as l", "as l arginine", "arginine l", "arg and", "and l lysine", "lysine l", "lys and", "cystine cyss", "the oxidised form", "oxidised form of", "form of l", "of l cysteine", "cysteine for", "for intracellular neutral", "intracellular neutral amino", "neutral amino acids", "as l leucine", "leucine l", "l leu .", "leu . these", ". these solute", "these solute carriers", "solute carriers are", "carriers are mainly", "are mainly expressed", "mainly expressed in", "expressed in the", "in the kidney", "the kidney and", "kidney and small", "and small intestine", "small intestine where", "intestine where they", "where they remove", "they remove dibasic", "remove dibasic amino", "acids and cystine", "and cystine from", "cystine from the", "from the renal", "the renal tubular", "renal tubular and", "tubular and intestinal", "and intestinal lumen", "intestinal lumen respectively", "respectively schweikhard", "schweikhard & ziegler", "& ziegler 2012", "ziegler 2012 .", "2012 . defects", ". defects in", "defects in slc3a1", "slc3a1 or", "slc7a9 can", "can cause cystinuria", "csnu mim:220100", "an autosomal recessive", "autosomal recessive disorder", "recessive disorder characterised", "disorder characterised by", "characterised by impaired", "by impaired epithelial", "impaired epithelial cell", "epithelial cell transport", "cell transport of", "transport of cystine", "of cystine and", "cystine and dibasic", "amino acids in", "acids in the", "in the proximal", "the proximal renal", "proximal renal tubule", "renal tubule and", "tubule and gi", "and gi tract.", "gi tract. the", "tract. the build", "the build up", "build up and", "up and low", "and low solubility", "low solubility of", "solubility of cystine", "of cystine causes", "cystine causes the", "causes the formation", "the formation of", "formation of calculi", "of calculi in", "calculi in the", "in the urinary", "the urinary tract", "tract resulting", "resulting in obstructive", "in obstructive uropathy", "uropathy pyelonephritis", "pyelonephritis and in", "and in severe", "in severe cases", "cases renal", "failure palacin", "palacin et al.", "et al. 2001", "2001 mattoo", "mattoo & goldfarb", "& goldfarb 2008", "2008 fotiadis", "fotiadis et al.", "et al. 2013", "2013 saravakos", "saravakos et al.", "et al. 2014", "al. 2014 .", "2014 . cystinuria", ". cystinuria is", "cystinuria is subcategorized", "is subcategorized as", "subcategorized as type", "as type a", "a mutations", "mutations on 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cystine. the slc7a9:slc3a1", "cystine. the slc7a9:slc3a1 heterodimer", "the slc7a9:slc3a1 heterodimer mediates", "slc7a9:slc3a1 heterodimer mediates the", "heterodimer mediates the electrogenic", "mediates the electrogenic exchange", "the electrogenic exchange of", "electrogenic exchange of extracellular", "exchange of extracellular amino", "of extracellular amino acids", "extracellular amino acids such", "amino acids such as", "acids such as l", "such as l arginine", "l arginine l", "arginine l arg", "l arg and", "arg and l", "l lysine l", "lysine l lys", "l lys and", "lys and cystine", "and cystine cyss", "cyss the", "the oxidised form of", "oxidised form of l", "form of l cysteine", "l cysteine for", "cysteine for intracellular", "for intracellular neutral amino", "intracellular neutral amino acids", "neutral amino acids such", "such as l leucine", "l leucine l", "leucine l leu", "l leu . these", "leu . these solute", ". these solute carriers", "these solute carriers are", "solute 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schweikhard &", "respectively schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . defects", "ziegler 2012 . defects in", "2012 . defects in slc3a1", "defects in slc3a1 or", "in slc3a1 or slc7a9", "or slc7a9 can cause", "slc7a9 can cause cystinuria", "can cause cystinuria csnu", "cystinuria csnu mim:220100", "mim:220100 an autosomal", "220100 an autosomal", "an autosomal recessive disorder characterised", "autosomal recessive disorder characterised by", "recessive disorder characterised by impaired", "disorder characterised by impaired epithelial", "characterised by impaired epithelial cell", "by impaired epithelial cell transport", "impaired epithelial cell transport of", "epithelial cell transport of cystine", "cell transport of cystine and", "transport of cystine and dibasic", "of cystine and dibasic amino", "cystine and dibasic amino acids", "and dibasic amino acids in", "dibasic amino acids in the", "amino acids in the proximal", "acids in the proximal renal", "in the proximal renal tubule", "the proximal renal tubule and", "proximal renal tubule and gi", "renal tubule and gi tract.", "tubule and gi tract. the", "and gi tract. the build", "gi tract. the build up", "tract. the build up and", "the build up and low", "build up and low solubility", "up and low solubility of", "and low solubility of cystine", "low solubility of cystine causes", "solubility of cystine causes the", "of cystine causes the formation", "cystine causes the formation of", "causes the formation of calculi", "the formation of calculi in", "formation of calculi in the", "of calculi in the urinary", "calculi in the urinary tract", "the urinary tract resulting", "urinary tract resulting in", "tract resulting in obstructive", "in obstructive uropathy pyelonephritis", "obstructive uropathy pyelonephritis and", "uropathy pyelonephritis and in", "pyelonephritis and in severe cases", "in severe cases renal", "severe cases renal failure", "renal failure palacin et", "failure 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required for the", "required for the addition", "for the addition of", "the addition of the", "addition of the second", "of the second n", "the second n acetylglucosamine", "n acetylglucosamine glcnac", "glcnac to the", "to the lipid linked", "the lipid linked oligosaccharide", "linked oligosaccharide llo", "glcnacdoldp gao", "gao et al. 2005", "et al. 2005 .", "al. 2005 . defects", "2005 . defects in", ". defects in alg14", "defects in alg14 can", "in alg14 can cause", "alg14 can cause congenital", "can cause congenital myasthenic", "cause congenital myasthenic syndrome", "myasthenic syndrome alg14", "syndrome alg14 cms", "cms which", "which is due to", "is due to a", "due to a defect", "to a defect in", "a defect in neuromuscular", "defect in neuromuscular signal", "in neuromuscular signal transmission", "signal transmission cossins", "transmission cossins et", "cossins et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the most", ". the most commonly", "the most commonly affected", "most commonly affected muscles", "commonly affected muscles include", "affected muscles include proximal", "muscles include proximal limb", "include proximal limb muscles.", "proximal limb muscles. mutations", "limb muscles. mutations causing", "muscles. mutations causing alg14", "mutations causing alg14 cms", "causing alg14 cms include", "alg14 cms include p.p65l", "cms include p.p65l and", "include p.p65l and p.r104*", "and p.r104* cossins", "p.r104* cossins et", "udp n acetylglucosamine transferase subunit", "n acetylglucosamine transferase subunit alg14", "acetylglucosamine transferase subunit alg14 homolog", "subunit alg14 homolog alg14", "homolog alg14 forms", "alg14 forms a complex", "forms a complex with alg13", "a complex with alg13 protein", "complex with alg13 protein and", "with alg13 protein and is", "alg13 protein and is required", "protein and is required for", "and is required for the", "is required for the addition", "required for the addition of", "for the addition of the", "the addition of the second", "addition of the second n", "of the second n acetylglucosamine", "second n acetylglucosamine glcnac", "acetylglucosamine glcnac to", "glcnac to the lipid", "to the lipid linked oligosaccharide", "lipid linked oligosaccharide llo", "oligosaccharide llo intermediate", "llo intermediate glcnacdoldp", "glcnacdoldp gao et", "gao et al. 2005 .", "et al. 2005 . defects", "al. 2005 . defects in", "2005 . defects in alg14", ". defects in alg14 can", "defects in alg14 can cause", "in alg14 can cause congenital", "alg14 can cause congenital myasthenic", "can cause congenital myasthenic syndrome", "congenital myasthenic syndrome alg14", "myasthenic syndrome alg14 cms", "alg14 cms which", "cms which is", "which is due to a", "is due to a defect", "due to a defect in", "to a defect in neuromuscular", "a defect in neuromuscular signal", "defect in neuromuscular signal transmission", "neuromuscular signal transmission cossins", "signal transmission cossins et", "transmission cossins et al.", "cossins et al. 2013 .", "et al. 2013 . the", "al. 2013 . the most", "2013 . the most commonly", ". the most commonly affected", "the most commonly affected muscles", "most commonly affected muscles include", "commonly affected muscles include proximal", "affected muscles include proximal limb", "muscles include proximal limb muscles.", "include proximal limb muscles. mutations", "proximal limb muscles. mutations causing", "limb muscles. mutations causing alg14", "muscles. mutations causing alg14 cms", "mutations causing alg14 cms include", "causing alg14 cms include p.p65l", "alg14 cms include p.p65l and", "cms include p.p65l and p.r104*", "p.p65l and p.r104* cossins", "and p.r104* cossins et", "p.r104* cossins et al." ] }, { "record_id": "GLY_000594_1_1761", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5655799", "r hsa", "hsa 5655799", "r hsa 5655799" ] }, { "record_id": "GLY_000594_1_1761", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc40a1", "slc40a1 causes", "causes hemochromatosis", "hemochromatosis 4", "defective slc40a1 causes", "slc40a1 causes hemochromatosis", "causes hemochromatosis 4", "4 hfe4", "defective slc40a1 causes hemochromatosis", "slc40a1 causes hemochromatosis 4", "hemochromatosis 4 hfe4", "hfe4 duodenum", "defective slc40a1 causes hemochromatosis 4", "causes hemochromatosis 4 hfe4", "the primary", "primary site", "site for", "for absorption", "absorption of", "of dietary", "dietary iron", "iron is", "is the", "the duodenum.", "duodenum. ferrous", "ferrous iron", "is taken", "taken up", "up from", "from the", "the gut", "gut lumen", "lumen across", "across the", "the apical", "apical membranes", "membranes of", "of enterocytes", "enterocytes and", "and released", "released into", "into the", "the portal", "portal vein", "vein circulation", "circulation across", "across basolateral", "basolateral membranes.", "membranes. the", "the human", "human gene", "gene slc40a1", "slc40a1 encodes", "encodes the", "the metal", "metal transporter", "transporter protein", "protein mtp1", "aka ferroportin", "ferroportin or", "or ireg1", "ireg1 .", ". this", "this protein", "protein resides", "resides on", "on the", "the basolateral", "basolateral membrane", "membrane of", "and mediates", "mediates ferrous", "iron efflux", "efflux into", "portal vein.", "vein. slc40a1", "slc40a1 colocalises", "colocalises with", "with hephaestin", "which stablises", "stablises it", "it and", "and is", "is necessary", "necessary for", "for the", "the efflux", "efflux reaction", "reaction to", "to occur.
              defects", "occur.
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              defects", "to occur.
              defects in", "occur.
              defects in slc40a1", "in slc40a1 can", "slc40a1 can cause", "can cause hemochromatosis", "cause hemochromatosis 4", "hfe4 mim:606069", "a disorder of", "disorder of iron", "of iron metabolism", "iron metabolism characterised", "metabolism characterised by", "characterised by iron", "by iron overload.", "iron overload. excess", "overload. excess iron", "excess iron is", "iron is deposited", "is deposited in", "deposited in a", "in a variety", "a variety of", "variety of organs", "of organs leading", "organs leading to", "leading to their", "to their failure", "failure resulting", "resulting in serious", "in serious illnesses", "serious illnesses including", "illnesses including cirrhosis", "cirrhosis hepatomas", "hepatomas diabetes", "diabetes cardiomyopathy", "cardiomyopathy arthritis", "arthritis and hypogonadotropic", "and hypogonadotropic hypogonadism.", "hypogonadotropic hypogonadism. severe", "hypogonadism. severe effects", "severe effects of", "effects of the", "of the disease", "the disease don't", "disease don't usually", "don't usually appear", "usually appear until", "appear until after", "until after decades", "after decades of", "decades of progressive", "of progressive iron", "progressive iron overloading", "de domenico et", "domenico et al.", "et al. 2005", "2005 2006", "2006 2011", "2011 kaplan", "kaplan et al.", "et al. 2011", "al. 2011 .", "the primary site for", "primary site for absorption", "site for absorption of", "for absorption of dietary", "absorption of dietary iron", "of dietary iron is", "dietary iron is the", "iron is the duodenum.", "is the duodenum. ferrous", "the duodenum. ferrous iron", "ferrous iron fe2+", "fe2+ is taken", "is taken up from", "taken up from the", "up from the gut", "from the gut lumen", "the gut lumen across", "gut lumen across the", "lumen across the apical", "across the apical membranes", "the apical membranes of", "apical membranes of enterocytes", "membranes of enterocytes and", "of enterocytes and released", "enterocytes and released into", "and released into the", "released into the portal", "into the portal vein", "the portal vein circulation", "portal vein circulation across", "vein circulation across basolateral", "circulation across basolateral membranes.", "across basolateral membranes. the", "basolateral membranes. the human", "membranes. the human gene", "the human gene slc40a1", "human gene slc40a1 encodes", "gene slc40a1 encodes the", "slc40a1 encodes the metal", "encodes the metal transporter", "the metal transporter protein", "metal transporter protein mtp1", "protein mtp1 aka", "mtp1 aka ferroportin", "aka ferroportin or ireg1", "ferroportin or ireg1 .", "or ireg1 . this", "ireg1 . this protein", ". this protein resides", "this protein resides on", "protein resides on the", "resides on the basolateral", "on the basolateral membrane", "the basolateral membrane of", "basolateral membrane of enterocytes", "membrane of enterocytes and", "of enterocytes and mediates", "enterocytes and mediates ferrous", "and mediates ferrous iron", "mediates ferrous iron efflux", "ferrous iron efflux into", "iron efflux into the", "efflux into the portal", "into the portal vein.", "the portal vein. slc40a1", "portal vein. slc40a1 colocalises", "vein. slc40a1 colocalises with", "slc40a1 colocalises with hephaestin", "with hephaestin heph", "heph which stablises", "which stablises it and", "stablises it and is", "it and is necessary", "and is necessary for", "is necessary for the", "necessary for the efflux", "for the efflux reaction", "the efflux reaction to", "efflux reaction to occur.
              defects", "reaction to occur.
              defects in", "to occur.
              defects in slc40a1", "occur.
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              defects", "efflux reaction to occur.
              defects in", "reaction to occur.
              defects in slc40a1", "to occur.
              defects in slc40a1 can", "occur.
              defects in slc40a1 can cause", "in slc40a1 can cause hemochromatosis", "slc40a1 can cause hemochromatosis 4", "cause hemochromatosis 4 hfe4", "4 hfe4 mim:606069", "mim:606069 a disorder", "606069 a disorder", "a disorder of iron metabolism", "disorder of iron metabolism characterised", "of iron metabolism characterised by", "iron metabolism characterised by iron", "metabolism characterised by iron overload.", "characterised by iron overload. excess", "by iron overload. excess iron", "iron overload. excess iron is", "overload. excess iron is deposited", "excess iron is deposited in", "iron is deposited in a", "is deposited in a variety", "deposited in a variety of", "in a variety of organs", "a variety of organs leading", "variety of organs leading to", "of organs leading to their", "organs leading to their failure", "to their failure resulting", "their failure resulting in", "failure resulting in serious", "resulting in serious illnesses including", "in serious illnesses including cirrhosis", "illnesses including cirrhosis hepatomas", "cirrhosis hepatomas diabetes", "hepatomas diabetes cardiomyopathy", "diabetes cardiomyopathy arthritis", "cardiomyopathy arthritis and hypogonadotropic", "arthritis and hypogonadotropic hypogonadism. severe", "and hypogonadotropic hypogonadism. severe effects", "hypogonadotropic hypogonadism. severe effects of", "hypogonadism. severe effects of the", "severe effects of the disease", "effects of the disease don't", "of the disease don't usually", "the disease don't usually appear", "disease don't usually appear until", "don't usually appear until after", "usually appear until after decades", "appear until after decades of", "until after decades of progressive", "after decades of progressive iron", "decades of progressive iron overloading", "iron overloading de", "overloading de domenico", "de domenico et al. 2005", "et al. 2005 2006", "2005 2006 2011", "2006 2011 kaplan", "2011 kaplan et al.", "kaplan et al. 2011 ." ] }, 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"ketohexokinase are associated with", "are associated with essential fructosuria", "with essential fructosuria bonthron", "essential fructosuria bonthron et", "fructosuria bonthron et al.", "bonthron et al. 1994 ." ] }, { "record_id": "GLY_000594_1_1763", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5658208", "r hsa", "hsa 5658208", "r hsa 5658208" ] }, { "record_id": "GLY_000594_1_1763", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc5a2", "slc5a2 causes", "causes renal", "renal glucosuria", "defective slc5a2 causes", "slc5a2 causes renal", "causes renal glucosuria", "glucosuria glys1", "defective slc5a2 causes renal", "slc5a2 causes renal glucosuria", "renal glucosuria glys1", "defective slc5a2 causes renal glucosuria", "causes renal glucosuria glys1", "the human", "human gene", "gene slc5a2", "slc5a2 encodes", "encodes a", "a sodium", "sodium dependent", "dependent glucose", 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"genotype\u2013phenotype correlations for glys1 is", "correlations for glys1 is made", "for glys1 is made difficult", "glys1 is made difficult by", "is made difficult by variable", "made difficult by variable expression", "difficult by variable expression of", "by variable expression of slc5a2", "variable expression of slc5a2 and", "expression of slc5a2 and because", "of slc5a2 and because other", "slc5a2 and because other genes", "and because other genes may", "because other genes may have", "other genes may have an", "genes may have an impact", "may have an impact on", "have an impact on overall", "an impact on overall renal", "impact on overall renal glucose", "on overall renal glucose resorption.", "overall renal glucose resorption. drugs", "renal glucose resorption. drugs that", "glucose resorption. drugs that inhibit", "resorption. drugs that inhibit slc5a2", "drugs that inhibit slc5a2 are", "that inhibit slc5a2 are used", "inhibit slc5a2 are used to", "slc5a2 are used to treat", "are used to treat type", "used to treat type 2", "to treat type 2 diabetes", "type 2 diabetes t2d", "2 diabetes t2d .", "diabetes t2d . the", "t2d . the strategy to", ". the strategy to reduce", "the strategy to reduce hyperglycemia", "strategy to reduce hyperglycemia in", "to reduce hyperglycemia in t2d", "reduce hyperglycemia in t2d is", "hyperglycemia in t2d is to", "in t2d is to target", "t2d is to target renal", "is to target renal glucose", "to target renal glucose reabsorption", "target renal glucose reabsorption by", "renal glucose reabsorption by inhibiting", "glucose reabsorption by inhibiting slc5a2", "by inhibiting slc5a2 santer", "inhibiting slc5a2 santer &", "slc5a2 santer & calado", "& calado 2010 calado", "calado 2010 calado et", "2010 calado et al.", "calado et al. 2011 ." ] }, { "record_id": "GLY_000594_1_1764", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5658471", "r hsa", "hsa 5658471", "r hsa 5658471" ] }, { "record_id": "GLY_000594_1_1764", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc5a7", "slc5a7 causes", "causes distal", "distal hereditary", "hereditary motor", "motor neuronopathy", "neuronopathy 7a", "defective slc5a7 causes", "slc5a7 causes distal", "causes distal hereditary", "distal hereditary motor", "hereditary motor neuronopathy", "motor neuronopathy 7a", "7a hmn7a", "defective slc5a7 causes distal", "slc5a7 causes distal hereditary", "causes distal hereditary motor", "distal hereditary motor neuronopathy", "hereditary motor neuronopathy 7a", "neuronopathy 7a hmn7a", "defective slc5a7 causes distal hereditary", "slc5a7 causes distal hereditary motor", "causes distal hereditary motor neuronopathy", "distal hereditary motor neuronopathy 7a", "motor neuronopathy 7a hmn7a", "the human", "human slc5a7", "slc5a7 gene", "gene encodes", "encodes a", "a sodium", "and chloride", "chloride dependent", "high affinity", "affinity 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the kidney specifically", "the kidney specifically the", "kidney specifically the s2/3", "specifically the s2/3 segments of", "the s2/3 segments of the", "s2/3 segments of the kidney", "segments of the kidney proximal", "of the kidney proximal tubule", "kidney proximal tubule broer", "proximal tubule broer &", "tubule broer & gether", "& gether 2012 schweikhard", "gether 2012 schweikhard &", "2012 schweikhard & ziegler", "schweikhard & ziegler 2012 .", "& ziegler 2012 . iminoglycinuria", "2012 . iminoglycinuria ig", "iminoglycinuria ig mim:242600", "ig mim:242600 or", "hyperglycinuria hg mim:138500", "hg mim:138500 can", "mim:138500 can arise from", "138500 can arise from", "can arise from defects in", "arise from defects in slc36a2", "defects in slc36a2 encoding", "in slc36a2 encoding a", "slc36a2 encoding a proton", "encoding a proton coupled amino", "a proton coupled amino acid", "proton coupled amino acid transporter", "coupled amino acid transporter 2", "acid transporter 2 pat2", "pat2 a high", "a high affinity cotransporter of", "high affinity cotransporter of glycine", "affinity cotransporter of glycine and", "cotransporter of glycine and proline.", "of glycine and proline. mutation", "glycine and proline. mutation in", "and proline. mutation in slc6a18", "proline. mutation in slc6a18 may", "mutation in slc6a18 may contribute", "in slc6a18 may contribute to", "slc6a18 may contribute to both", "may contribute to both ig", "contribute to both ig and", "to both ig and hg", "ig and hg broer", "and hg broer et", "hg broer et al.", "broer et al. 2008 ." ] }, { "record_id": "GLY_000594_1_1766", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5659735", "r hsa", "hsa 5659735", "r hsa 5659735" ] }, { "record_id": "GLY_000594_1_1766", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc6a19", "slc6a19 causes", "causes hartnup", "hartnup disorder", "defective slc6a19 causes", "slc6a19 causes hartnup", "causes hartnup disorder", "disorder hnd", "defective slc6a19 causes hartnup", "slc6a19 causes hartnup disorder", "hartnup disorder hnd", "defective slc6a19 causes hartnup disorder", "causes hartnup disorder hnd", "slc6a19 encodes", "encodes the", "the sodium", "sodium dependent", "dependent neutral", "neutral amino", "amino acid", "acid transporter", "transporter b", "b 0", "0 at1", "at1 and", "and mediates", "mediates the", "the uptake", "uptake of", "of neutral", "amino acids", "acids across", "across the", "the plasma", "plasma membrane", "membrane accompanied", "accompanied by", "by uptake", "of a", "a sodium", "sodium ion.", "ion. the", "the protein", "protein is", "is abundantly", "abundantly expressed", "expressed in", "in the", "the small", "small intestine", "intestine and", "and kidney", "broer &", "& gether", "gether 2012", "schweikhard &", "& ziegler", "ziegler 2012", "2012 .", ". defects", "defects in", "in slc6a19", "slc6a19 can", "can cause", "cause hartnup", "an autosomal", "autosomal recessive", "recessive abnormality", "abnormality of", "of renal", "renal and", "and gastrointestinal", "gastrointestinal neutral", "acid transport", "transport characterised", "characterised by", "by increased", "increased urinary", "urinary and", "and intestinal", "intestinal excretion", "excretion of", "amino acids.", "acids. symptoms", "symptoms include", "include transient", "transient manifestations", "manifestations of", "of rashes", "cerebellar ataxia", "ataxia and", "and psychotic", "psychotic behaviour", "broer 2009", "cheon et", "et al.", "al. 2010", "2010 .", ". some", "some mutations", "mutations in", "slc6a19 are", "are thought", "thought to", "to contribute", "contribute to", "to the", "the phenotypes", "phenotypes iminoglycinuria", "and hyperglycinuria", "broer et", "al. 2008", "2008 .", "slc6a19 encodes the", "encodes the sodium", "the sodium dependent", "sodium dependent neutral", "dependent neutral amino", "neutral 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mim:234500", "an autosomal recessive", "autosomal recessive abnormality", "recessive abnormality of", "abnormality of renal", "of renal and", "renal and gastrointestinal", "and gastrointestinal neutral", "gastrointestinal neutral amino", "amino acid transport", "acid transport characterised", "transport characterised by", "characterised by increased", "by increased urinary", "increased urinary and", "urinary and intestinal", "and intestinal excretion", "intestinal excretion of", "excretion of neutral", "neutral amino acids.", "amino acids. symptoms", "acids. symptoms include", "symptoms include transient", "include transient manifestations", "transient manifestations of", "manifestations of rashes", "rashes cerebellar", "cerebellar ataxia and", "ataxia and psychotic", "and psychotic behaviour", "behaviour broer", "2009 cheon", "cheon et al.", "et al. 2010", "al. 2010 .", "2010 . some", ". some mutations", "some mutations in", "mutations in slc6a19", "in slc6a19 are", "slc6a19 are thought", "are thought to", "thought to contribute", "to contribute to", "contribute to the", "to the phenotypes", "the phenotypes iminoglycinuria", "iminoglycinuria ig", "ig mim:242600", "mim:242600 and", "242600 and", "hyperglycinuria hg", "hg mim:138500", "broer et al.", "et al. 2008", "al. 2008 .", "slc6a19 encodes the sodium", "encodes the sodium dependent", "the sodium dependent neutral", "sodium dependent neutral amino", "dependent neutral amino acid", "neutral amino acid transporter", "amino acid transporter b", "acid transporter b 0", "transporter b 0 at1", "b 0 at1 and", "0 at1 and mediates", "at1 and mediates the", "and mediates the uptake", "mediates the uptake of", "the uptake of neutral", "uptake of neutral amino", "of neutral amino acids", "neutral amino acids across", "amino acids across the", "acids across the plasma", "across the plasma membrane", "the plasma membrane accompanied", "plasma membrane accompanied by", "membrane accompanied by uptake", "accompanied by 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"gastrointestinal neutral amino acid", "neutral amino acid transport", "amino acid transport characterised", "acid transport characterised by", "transport characterised by increased", "characterised by increased urinary", "by increased urinary and", "increased urinary and intestinal", "urinary and intestinal excretion", "and intestinal excretion of", "intestinal excretion of neutral", "excretion of neutral amino", "of neutral amino acids.", "neutral amino acids. symptoms", "amino acids. symptoms include", "acids. symptoms include transient", "symptoms include transient manifestations", "include transient manifestations of", "transient manifestations of rashes", "of rashes cerebellar", "rashes cerebellar ataxia", "cerebellar ataxia and psychotic", "ataxia and psychotic behaviour", "psychotic behaviour broer", "behaviour broer 2009", "broer 2009 cheon", "2009 cheon et", "cheon et al. 2010", "et al. 2010 .", "al. 2010 . some", "2010 . some mutations", ". some mutations in", "some mutations in slc6a19", "mutations in slc6a19 are", "in slc6a19 are thought", "slc6a19 are thought to", "are thought to contribute", "thought to contribute to", "to contribute to the", "contribute to the phenotypes", "to the phenotypes iminoglycinuria", "phenotypes iminoglycinuria ig", "mim:242600 and hyperglycinuria", "242600 and hyperglycinuria", "and hyperglycinuria hg", "mim:138500 broer", "138500 broer", "broer et al. 2008", "et al. 2008 .", "slc6a19 encodes the sodium dependent", "encodes the sodium dependent neutral", "the sodium dependent neutral amino", "sodium dependent neutral amino acid", "dependent neutral amino acid transporter", "neutral amino acid transporter b", "amino acid transporter b 0", "acid transporter b 0 at1", "transporter b 0 at1 and", "b 0 at1 and mediates", "0 at1 and mediates the", "at1 and mediates the uptake", "and mediates the uptake of", "mediates the uptake of neutral", "the uptake of neutral amino", "uptake of neutral amino acids", "of neutral amino 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the genetic", "slc6a19 constitute the genetic basis", "constitute the genetic basis for", "the genetic basis for these", "genetic basis for these phenotypes." ] }, { "record_id": "GLY_000594_1_1769", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5660724", "r hsa", "hsa 5660724", "r hsa 5660724" ] }, { "record_id": "GLY_000594_1_1769", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective slc6a3", "slc6a3 causes", "causes parkinsonism", "parkinsonism dystonia", "dystonia infantile", "defective slc6a3 causes", "slc6a3 causes parkinsonism", "causes parkinsonism dystonia", "parkinsonism dystonia infantile", "infantile pkdys", "defective slc6a3 causes parkinsonism", "slc6a3 causes parkinsonism dystonia", "causes parkinsonism dystonia infantile", "dystonia infantile pkdys", "defective slc6a3 causes parkinsonism dystonia", "slc6a3 causes parkinsonism dystonia infantile", "parkinsonism dystonia 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"defective slc7a9 causes", "slc7a9 causes cystinuria", "cystinuria csnu", "defective slc7a9 causes cystinuria", "causes cystinuria csnu", "slc7a9 causes cystinuria csnu", "slc7a9 encodes", "encodes the", "the b", "b 0", "0 +", "type amino", "amino acid", "acid transporter", "transporter 1", "1 bat1.", "bat1. as", "as a", "a heterodimer", "heterodimer with", "with slc3a1", "slc3a1 in", "in the", "the plasma", "plasma membrane", "slc7a9 mediates", "mediates the", "the high", "high affinity", "sodium independent", "independent transport", "transport of", "of cystine", "the oxidised", "oxidised form", "form of", "of l", "l cysteine", "and dibasic", "dibasic amino", "amino acids", "acids in", "in exchange", "exchange for", "for neutral", "neutral amino", "acids and", "and is", "is thought", "thought to", "to be", "be responsible", "responsible for", "for the", "the reabsorption", "reabsorption of", "of cyss", "the kidney", "kidney tubule", "schweikhard &", "& ziegler", "ziegler 2012", "2012 .", ". defects", "defects in", "in slc7a9", "or slc3a1", "can cause", "cause cystinuria", "an autosomal", "autosomal disorder", "disorder characterised", "characterised by", "by impaired", "impaired renal", "renal reabsorption", "cystine and", "amino acids.", "acids. the", "the low", "low solubility", "solubility of", "cystine causes", "causes the", "the formation", "formation of", "of calculi", "calculi in", "the urinary", "urinary tract", "tract resulting", "resulting in", "in obstructive", "obstructive uropathy", "renal failure", "palacin et", "et al.", "al. 2001", "mattoo &", "& goldfarb", "goldfarb 2008", "fotiadis et", "al. 2013", "saravakos et", "al. 2014", "barbosa et", "al. 2012", ". cystinuria", "cystinuria is", "is subcategorised", "subcategorised as", "as type", "type a", "mutations on", "on slc3a1", "and type", "type b", "on slc7a9", "slc7a9 .", "slc7a9 encodes the", "encodes the b", "the b 0", "b 0 +", "+ type", "type amino acid", "amino acid transporter", "acid 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goldfarb", "& goldfarb 2008", "2008 fotiadis", "fotiadis et al.", "et al. 2013", "2013 saravakos", "saravakos et al.", "et al. 2014", "2014 barbosa", "barbosa et al.", "et al. 2012", "al. 2012 .", "2012 . cystinuria", ". cystinuria is", "cystinuria is subcategorised", "is subcategorised as", "subcategorised as type", "as type a", "a mutations", "mutations on slc3a1", "slc3a1 and", "and type b", "b mutations", "mutations on slc7a9", "on slc7a9 .", "slc7a9 encodes the b", "encodes the b 0", "the b 0 +", "0 + type", "+ type amino", "type amino acid transporter", "amino acid transporter 1", "acid transporter 1 bat1.", "transporter 1 bat1. as", "1 bat1. as a", "bat1. as a heterodimer", "as a heterodimer with", "a heterodimer with slc3a1", "heterodimer with slc3a1 in", "with slc3a1 in the", "slc3a1 in the plasma", "in the plasma membrane", "plasma membrane slc7a9", "membrane slc7a9 mediates", "slc7a9 mediates the high", "mediates the high affinity", "high affinity sodium", "affinity sodium 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fotiadis", "goldfarb 2008 fotiadis et", "2008 fotiadis et al.", "et al. 2013 saravakos", "al. 2013 saravakos et", "2013 saravakos et al.", "et al. 2014 barbosa", "al. 2014 barbosa et", "2014 barbosa et al.", "barbosa et al. 2012 .", "et al. 2012 . cystinuria", "al. 2012 . cystinuria is", "2012 . cystinuria is subcategorised", ". cystinuria is subcategorised as", "cystinuria is subcategorised as type", "is subcategorised as type a", "as type a mutations", "type a mutations on", "a mutations on slc3a1", "mutations on slc3a1 and", "on slc3a1 and type", "slc3a1 and type b", "and type b mutations", "type b mutations on", "b mutations on slc7a9" ] }, { "record_id": "GLY_000594_1_1771", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5662853", "r hsa", "hsa 5662853", "r hsa 5662853" ] }, { "record_id": "GLY_000594_1_1771", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "essential pentosuria", "the 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inactivated by", "inactivated by gene", "by gene deletion", "gene deletion or", "deletion or epigenetic", "or epigenetic silencing", "silencing or", "or indirectly by", "indirectly by overexpression", "by overexpression of", "overexpression of micrornas", "of micrornas that", "micrornas that target", "that target pten", "target pten mrna", "mrna huse", "huse et al.", "et al. 2009", "al. 2009 .", "2009 . cells", ". cells with", "cells with deficient", "with deficient pten", "deficient pten function", "pten function have", "function have increased", "have increased levels", "increased levels of", "levels of pip3", "pip3 and", "and therefore increased", "therefore increased akt", "increased akt activity.", "akt activity. for", "activity. for a", "for a recent", "a recent review", "review please", "please refer to", "refer to hollander", "to hollander et", "hollander et al.", "et al. 2011.", "loss of function mutations", "of function mutations affecting", "function mutations affecting 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and efficiency", "high affinity and efficiency mono", "and efficiency mono and", "efficiency mono and di", "mono and di glucuronated", "and di glucuronated bilirubin into", "di glucuronated bilirubin into bile.", "glucuronated bilirubin into bile. bilirubin", "into bile. bilirubin the", "bile. bilirubin the end", "bilirubin the end product", "the end product of heme", "end product of heme breakdown", "of heme breakdown is", "heme breakdown is an", "breakdown is an important", "is an important constituent of", "an important constituent of bile", "important constituent of bile and", "constituent of bile and is", "of bile and is responsible", "bile and is responsible for", "and is responsible for its", "is responsible for its characteristic", "responsible for its characteristic colour.", "for its characteristic colour. defects", "its characteristic colour. defects in", "characteristic colour. defects in abcc2", "colour. defects in abcc2 can", "defects in abcc2 can cause", "in abcc2 can cause dubin", "abcc2 can cause dubin johnson", "can cause dubin johnson syndrome", "dubin johnson syndrome djs", "syndrome djs mim:237500", "mim:237500 an autosomal", "237500 an autosomal", "an autosomal recessive disorder characterised", "autosomal recessive disorder characterised by", "recessive disorder characterised by conjugated", "disorder characterised by conjugated hyperbilirubinemia", "by conjugated hyperbilirubinemia dubin", "conjugated hyperbilirubinemia dubin &", "hyperbilirubinemia dubin & johnson", "& johnson 1954 keppler", "johnson 1954 keppler 2014", "keppler 2014 erlinger et", "2014 erlinger et al.", "erlinger et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1775", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5679090", "r hsa", "hsa 5679090", "r hsa 5679090" ] }, { "record_id": "GLY_000594_1_1775", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abcg8", "abcg8 causes", "causes gbd4", "gbd4 and", "and sitosterolemia", "defective abcg8 causes", "abcg8 causes gbd4", "causes gbd4 and", "gbd4 and sitosterolemia", "defective abcg8 causes gbd4", "abcg8 causes gbd4 and", "causes gbd4 and sitosterolemia", "defective abcg8 causes gbd4 and", "abcg8 causes gbd4 and sitosterolemia", "atp binding", "binding cassette", "cassette sub", "sub family", "family g", "g member", "member 8", "abcg8 aka", "aka sterolin", "sterolin 2", "is a", "a \\half", "\\half transporter\\", "that forms", "forms a", "a complex", "complex with", "with another", "another half", "half transporter", "transporter abcg5", "abcg5 in", "in the", "the endoplasmic", "endoplasmic reticulum.", "reticulum. this", "this complex", "complex translocates", "translocates to", "to the", "the plasma", "plasma membrane", "membrane to", "to mediate", "mediate the", "the atp", "atp dependent", "dependent intestinal", "intestinal absorption", "absorption and", "and facilitation", "facilitation of", "of biliary", "biliary secretion", "secretion of", "of cholesterol", "cholesterol and", "and phytosterols", "eg sitosterol", "sitosterol .", ". defects", "defects in", "in either", "either of", "of these", "these half", "half transporters", "transporters result", "result in", "in loss", "loss of", "of enterocyte", "enterocyte discrimination", "discrimination between", "between cholesterol", "and sitosterol", "sitosterol causing", "causing sterol", "sterol accumulation", "accumulation and", "and predisposition", "predisposition for", "for atherosclerosis.", "atherosclerosis. defects", "in abcg8", "abcg8 are", "are the", "the cause", "cause of", "of gallbladder", "gallbladder disease", "disease 4", "one of", "of the", "the major", "major digestive", "digestive diseases.", "diseases. gallstones", "gallstones are", "are composed", "composed of", "and are", "the common", "common manifestations", "manifestations of", "of gbd", "gbd in", "in western", "western countries", "buch et", "et al.", "al. 2007", "rudkowska &", "& jones", "jones 2008", "jakulj et", "al. 2010", "2010 .", "abcg8 also", "also cause", "cause sitosterolemia", "characterised by", "by unrestricted", "unrestricted intestinal", "absorption of", "of both", "both cholesterol", "and plant", "plant derived", "derived sterols", "sterols causing", "causing hypercholesterolemia", "hypercholesterolemia and", "and premature", "premature coronary", "coronary atherosclerosis.", "atherosclerosis. patients", "patients with", "with sitosterolemia", "sitosterolemia absorb", "absorb between", "between 15", "15 and", "and 60%", "60% of", "of ingested", "ingested sitosterol", "and they", "they excrete", "excrete only", "only a", "a fraction", "fraction into", "into the", "the bile", "berge et", "al. 2000", "othman et", "al. 2013", "yu et", "al. 2014", "2014 .", "atp binding cassette", "binding cassette sub", "cassette sub family", "sub family g", "family g member", "g member 8", "8 abcg8", "abcg8 aka sterolin", "aka sterolin 2", "is a \\half", "a \\half transporter\\", "transporter\\ that", "that forms a", "forms a complex", "a complex with", "complex with another", "with another half", "another half transporter", "half transporter abcg5", "transporter abcg5 in", "abcg5 in the", "in the endoplasmic", "the endoplasmic reticulum.", "endoplasmic reticulum. this", "reticulum. this complex", "this complex translocates", "complex translocates to", "translocates to the", "to the plasma", "the plasma membrane", "plasma membrane to", "membrane to mediate", "to mediate the", "mediate the atp", "the atp dependent", "atp dependent intestinal", "dependent intestinal absorption", "intestinal absorption and", "absorption and facilitation", "and facilitation of", "facilitation of biliary", "of biliary secretion", "biliary secretion of", "secretion of cholesterol", "of cholesterol and", "cholesterol and phytosterols", "phytosterols eg", "eg sitosterol .", "sitosterol . defects", ". defects in", "defects in either", "in 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of", "composed of cholesterol", "cholesterol cholelithiasis", "cholelithiasis and", "and are the", "are the common", "the common manifestations", "common manifestations of", "manifestations of gbd", "of gbd in", "gbd in western", "in western countries", "countries buch", "buch et al.", "et al. 2007", "2007 rudkowska", "rudkowska & jones", "& jones 2008", "2008 jakulj", "jakulj et al.", "et al. 2010", "al. 2010 .", "2010 . defects", "in abcg8 also", "abcg8 also cause", "also cause sitosterolemia", "sitosterolemia mim:210250", "characterised by unrestricted", "by unrestricted intestinal", "unrestricted intestinal absorption", "intestinal absorption of", "absorption of both", "of both cholesterol", "both cholesterol and", "cholesterol and plant", "and plant derived", "plant derived sterols", "derived sterols causing", "sterols causing hypercholesterolemia", "causing hypercholesterolemia and", "hypercholesterolemia and premature", "and premature coronary", "premature coronary atherosclerosis.", "coronary atherosclerosis. patients", "atherosclerosis. patients with", "patients with sitosterolemia", "with sitosterolemia absorb", "sitosterolemia absorb between", "absorb between 15", "between 15 and", "15 and 60%", "and 60% of", "60% of ingested", "of ingested sitosterol", "sitosterol and", "and they excrete", "they excrete only", "excrete only a", "only a fraction", "a fraction into", "fraction into the", "into the bile", "bile berge", "berge et al.", "et al. 2000", "2000 othman", "othman et al.", "et al. 2013", "2013 yu", "yu et al.", "et al. 2014", "al. 2014 .", "atp binding cassette sub", "binding cassette sub family", "cassette sub family g", "sub family g member", "family g member 8", "member 8 abcg8", "8 abcg8 aka", "abcg8 aka sterolin 2", "2 is", "is a \\half transporter\\", "\\half transporter\\ that", "transporter\\ that forms", "that forms a complex", "forms a complex with", "a complex with another", "complex with another half", "with another half 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"sitosterol . defects in", ". defects in either", "defects in either of", "in either of these", "either of these half", "of these half transporters", "these half transporters result", "half transporters result in", "transporters result in loss", "result in loss of", "in loss of enterocyte", "loss of enterocyte discrimination", "of enterocyte discrimination between", "enterocyte discrimination between cholesterol", "discrimination between cholesterol and", "between cholesterol and sitosterol", "cholesterol and sitosterol causing", "and sitosterol causing sterol", "sitosterol causing sterol accumulation", "causing sterol accumulation and", "sterol accumulation and predisposition", "accumulation and predisposition for", "and predisposition for atherosclerosis.", "predisposition for atherosclerosis. defects", "for atherosclerosis. defects in", "atherosclerosis. defects in abcg8", "defects in abcg8 are", "in abcg8 are the", "abcg8 are the cause", "are the cause of", "the cause of 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"bile berge et al.", "et al. 2000 othman", "al. 2000 othman et", "2000 othman et al.", "et al. 2013 yu", "al. 2013 yu et", "2013 yu et al.", "yu et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1776", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5679096", "r hsa", "hsa 5679096", "r hsa 5679096" ] }, { "record_id": "GLY_000594_1_1776", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abcg5", "abcg5 causes", "causes sitosterolemia", "defective abcg5 causes", "abcg5 causes sitosterolemia", "defective abcg5 causes sitosterolemia", "atp binding", "binding cassette", "cassette sub", "sub family", "family g", "g member", "member 5", "abcg5 aka", "aka sterolin", "sterolin 1", "is a", "a \\half", "\\half transporter\\", "that forms", "forms a", "a complex", "complex with", "with another", "another half", "half transporter", "transporter abcg8", "sterolin 2", "in the", "the endoplasmic", 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atherosclerosis. defects in", "atherosclerosis. defects in abcg5", "defects in abcg5 are", "in abcg5 are the", "abcg5 are the cause", "are the cause of", "the cause of sitosterolemia", "of sitosterolemia mim:210250", "mim:210250 characterised", "210250 characterised", "characterised by unrestricted intestinal", "by unrestricted intestinal absorption", "unrestricted intestinal absorption of", "intestinal absorption of both", "absorption of both cholesterol", "of both cholesterol and", "both cholesterol and plant", "cholesterol and plant derived", "and plant derived sterols", "plant derived sterols causing", "derived sterols causing hypercholesterolemia", "sterols causing hypercholesterolemia and", "causing hypercholesterolemia and premature", "hypercholesterolemia and premature coronary", "and premature coronary atherosclerosis.", "premature coronary atherosclerosis. patients", "coronary atherosclerosis. patients with", "atherosclerosis. patients with sitosterolemia", "patients with sitosterolemia absorb", "with sitosterolemia absorb between", "sitosterolemia absorb between 15", "absorb between 15 and", "between 15 and 60%", "15 and 60% of", "and 60% of ingested", "60% of ingested sitosterol", "of ingested sitosterol and", "ingested sitosterol and excrete", "sitosterol and excrete only", "and excrete only a", "excrete only a fraction", "only a fraction of", "a fraction of this", "fraction of this into", "of this into the", "this into the bile", "the bile berge", "bile berge et", "berge et al. 2000", "al. 2000 othman", "2000 othman et", "othman et al. 2013", "al. 2013 yu", "2013 yu et", "yu et al. 2014", "et al. 2014 .", "atp binding cassette sub family", "binding cassette sub family g", "cassette sub family g member", "sub family g member 5", "g member 5 abcg5", "member 5 abcg5 aka", "5 abcg5 aka sterolin", "sterolin 1 is", "1 is a", "a \\half transporter\\ that", "\\half transporter\\ that forms", "transporter\\ that forms a", "that forms a complex with", "forms a complex with another", "a complex with another half", "complex with another half transporter", "with another half transporter abcg8", "half transporter abcg8 aka", "transporter abcg8 aka sterolin", "abcg8 aka sterolin 2", "aka sterolin 2 in", "sterolin 2 in the", "2 in the endoplasmic", "in the endoplasmic reticulum. this", "the endoplasmic reticulum. this complex", "endoplasmic reticulum. this complex translocates", "reticulum. this complex translocates to", "this complex translocates to the", "complex translocates to the plasma", "translocates to the plasma membrane", "to the plasma membrane to", "the plasma membrane to mediate", "plasma membrane to mediate the", "membrane to mediate the atp", "to mediate the atp dependent", "mediate the atp dependent intestinal", "the atp dependent intestinal absorption", "atp dependent intestinal absorption and", "dependent intestinal absorption and facilitation", "intestinal absorption and facilitation of", "absorption and facilitation of biliary", "and facilitation of biliary secretion", "facilitation of biliary secretion of", "of biliary secretion of cholesterol", "biliary secretion of cholesterol and", "secretion of cholesterol and phytosterols", "cholesterol and phytosterols e.g.", "and phytosterols e.g. sitosterol", "phytosterols e.g. sitosterol .", "e.g. sitosterol . defects in", "sitosterol . defects in either", ". defects in either of", "defects in either of these", "in either of these half", "either of these half transporters", "of these half transporters result", "these half transporters result in", "half transporters result in loss", "transporters result in loss of", "result in loss of enterocyte", "in loss of enterocyte discrimination", "loss of enterocyte discrimination between", "of enterocyte discrimination between cholesterol", "enterocyte discrimination between cholesterol and", "discrimination between cholesterol and sitosterol", "between cholesterol and sitosterol causing", "cholesterol and sitosterol causing sterol", "and sitosterol causing sterol accumulation", "sitosterol causing sterol accumulation and", "causing sterol accumulation and predisposition", "sterol accumulation and predisposition for", "accumulation and predisposition for atherosclerosis.", "and predisposition for atherosclerosis. defects", "predisposition for atherosclerosis. defects in", "for atherosclerosis. defects in abcg5", "atherosclerosis. defects in abcg5 are", "defects in abcg5 are the", "in abcg5 are the cause", "abcg5 are the cause of", "are the cause of sitosterolemia", "cause of sitosterolemia mim:210250", "mim:210250 characterised by", "210250 characterised by", "characterised by unrestricted intestinal absorption", "by unrestricted intestinal absorption of", "unrestricted intestinal absorption of both", "intestinal absorption of both cholesterol", "absorption of both cholesterol and", "of both cholesterol and plant", "both cholesterol and plant derived", "cholesterol and plant derived sterols", "and plant derived sterols causing", "plant derived sterols causing hypercholesterolemia", "derived sterols causing hypercholesterolemia and", "sterols causing hypercholesterolemia and premature", "causing hypercholesterolemia and premature coronary", "hypercholesterolemia and premature coronary atherosclerosis.", "and premature coronary atherosclerosis. patients", "premature coronary atherosclerosis. patients with", "coronary atherosclerosis. patients with sitosterolemia", "atherosclerosis. patients with sitosterolemia absorb", "patients with sitosterolemia absorb between", "with sitosterolemia absorb between 15", "sitosterolemia absorb between 15 and", "absorb between 15 and 60%", "between 15 and 60% of", "15 and 60% of ingested", "and 60% of ingested sitosterol", "60% of ingested sitosterol and", "of ingested sitosterol and excrete", "ingested sitosterol and excrete only", "sitosterol and excrete only a", "and excrete only a fraction", "excrete only a fraction of", "only a fraction of this", "a fraction of this into", "fraction of this into the", "of this into the bile", "into the bile berge", "the bile berge et", "bile berge et al.", "et al. 2000 othman", "al. 2000 othman et", "2000 othman et al.", "et al. 2013 yu", "al. 2013 yu et", "2013 yu et al.", "yu et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1777", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5682294", "r hsa", "hsa 5682294", "r hsa 5682294" ] }, { "record_id": "GLY_000594_1_1777", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abca12", "abca12 causes", "causes arci4b", "defective abca12 causes", "abca12 causes arci4b", "defective abca12 causes arci4b", "atp binding", "binding cassette", "cassette sub", "sub family", "family a", "a member", "member 12", "is thought", "thought to", "to function", "function as", "as an", "an epidermal", "epidermal keratinocyte", "keratinocyte lipid", "lipid transporter.", "transporter. these", "these lipids", "lipids form", "form extracellular", "extracellular lipid", "lipid layers", "layers in", "in the", "the stratum", "stratum corneum", "corneum of", "of the", "the epidermis", "essential for", "for skin", "skin barrier", "barrier function.", "function. defects", "defects in", "in abca12", "abca12 results", "results in", "the loss", "loss of", "the skin", "skin lipid", "lipid barrier", "leading to", "to autosomal", "autosomal recessive", "recessive congenital", "congenital ichthyosis", "ichthyosis 4b", "aka harlequin", "harlequin ichthyosis", "hi .", ". arci4b", "arci4b shows", "shows the", "the most", "most severe", "severe phenotype", "phenotype of", "the congenital", "congenital ichthyoses", "with newborns", "newborns having", "having a", "a thick", "thick covering", "covering of", "of armour", "armour like", "like scales.", "scales. the", "skin dries", "dries out", "out to", "to form", "form hard", "hard diamond", "diamond shaped", "shaped plaques", "plaques separated", "separated by", "by fissures.", "fissures. affected", "affected babies", "babies are", "are often", "often born", "born prematurely", "prematurely and", "and rarely", "rarely survive", "survive the", "the perinatal", "perinatal period", "akiyama et", "et al.", "al. 2005", "akiyama 2010", "2014 .", "atp binding cassette", "binding cassette sub", "cassette sub family", "sub family a", "family a member", "a member 12", "12 abca12", "abca12 is", "is thought to", "thought to function", "to function as", "function as an", "as an epidermal", "an epidermal keratinocyte", "epidermal keratinocyte lipid", "keratinocyte lipid transporter.", "lipid transporter. these", "transporter. these lipids", "these lipids form", "lipids form extracellular", "form extracellular lipid", "extracellular lipid layers", "lipid layers in", "layers in the", "in the stratum", "the stratum corneum", "stratum corneum of", "corneum of the", "of the epidermis", "epidermis essential", "essential for skin", "for skin barrier", "skin barrier function.", "barrier function. defects", "function. defects in", "defects in abca12", "in abca12 results", "abca12 results in", "results in the", "in the loss", "the loss of", "loss of the", "of the skin", "the skin lipid", "skin lipid barrier", "barrier leading", "leading to autosomal", "to autosomal recessive", "autosomal recessive congenital", "recessive congenital ichthyosis", "congenital ichthyosis 4b", "4b arci4b", "arci4b mim:242500", "mim:242500 aka", "242500 aka", "aka harlequin ichthyosis", "ichthyosis hi", "hi . arci4b", ". arci4b shows", "arci4b shows the", "shows the most", "the most severe", "most severe phenotype", "severe phenotype of", "phenotype of the", "of the congenital", "the congenital ichthyoses", "ichthyoses with", "with newborns having", "newborns having a", "having a thick", "a thick covering", "thick covering of", "covering of armour", "of armour like", "armour like scales.", "like scales. the", "scales. the skin", "the skin dries", "skin dries out", "dries out to", "out to form", "to form hard", "form hard diamond", "hard diamond shaped", "diamond shaped plaques", "shaped plaques separated", "plaques separated by", "separated by fissures.", "by fissures. affected", "fissures. affected babies", "affected babies are", "babies are often", "are often born", "often born prematurely", "born prematurely and", "prematurely and rarely", "and rarely survive", "rarely survive the", "survive the perinatal", "the perinatal period", "period akiyama", "akiyama et al.", "et al. 2005", "2005 akiyama", "2010 2014", "atp binding cassette sub", "binding cassette sub family", "cassette sub family a", "sub family a member", "family a member 12", "member 12 abca12", "abca12 is thought", "is thought to function", "thought to function as", "to function as an", "function as an epidermal", "as an epidermal keratinocyte", "an epidermal keratinocyte lipid", "epidermal keratinocyte lipid transporter.", "keratinocyte lipid transporter. these", "lipid transporter. these lipids", "transporter. these lipids form", "these lipids form extracellular", "lipids form extracellular lipid", "form extracellular lipid layers", "extracellular lipid layers in", "lipid layers in the", "layers in the stratum", "in the stratum corneum", "the stratum corneum of", "stratum corneum of the", "corneum of the epidermis", "the epidermis essential", "epidermis essential for", "essential for skin barrier", "for skin barrier function.", "skin barrier function. defects", "barrier function. defects in", "function. defects in abca12", "defects in abca12 results", "in abca12 results in", "abca12 results in the", "results in the loss", "in the loss of", "the loss of the", "loss of the skin", "of the skin lipid", "the skin lipid barrier", "lipid barrier leading", "barrier leading to", "leading to autosomal recessive", "to autosomal recessive congenital", "autosomal recessive congenital ichthyosis", "recessive congenital ichthyosis 4b", "ichthyosis 4b arci4b", "mim:242500 aka harlequin", "242500 aka harlequin", "harlequin ichthyosis hi", "ichthyosis hi .", "hi . arci4b shows", ". arci4b shows the", "arci4b shows the most", "shows the most severe", "the most severe phenotype", "most severe phenotype of", "severe phenotype of the", "phenotype of the congenital", "of the congenital ichthyoses", "congenital ichthyoses with", "ichthyoses with newborns", "with newborns having a", "newborns having a thick", "having a thick covering", "a thick covering of", "thick covering of armour", "covering of armour like", "of armour like scales.", "armour like scales. the", "like scales. the skin", "scales. the skin dries", "the skin dries out", "skin dries out to", "dries out to form", "out to form hard", "to form hard diamond", "form hard diamond shaped", "hard diamond shaped plaques", "diamond shaped plaques separated", "shaped plaques separated by", "plaques separated by fissures.", "separated by fissures. affected", "by fissures. affected babies", "fissures. affected babies are", "affected babies are often", "babies are often born", "are often born prematurely", "often born prematurely and", "born prematurely and rarely", "prematurely and rarely survive", "and rarely survive the", "rarely survive the perinatal", "survive the perinatal period", "perinatal period akiyama", "period akiyama et", "akiyama et al. 2005", "al. 2005 akiyama", "2005 akiyama 2010", "akiyama 2010 2014", "2010 2014 .", "atp binding cassette sub family", "binding cassette sub family a", "cassette sub family a member", "sub family a member 12", "a member 12 abca12", "12 abca12 is", "abca12 is thought to", "is thought to function as", "thought to function as an", "to function as an epidermal", "function as an epidermal keratinocyte", "as an epidermal keratinocyte lipid", "an epidermal keratinocyte lipid transporter.", "epidermal keratinocyte lipid transporter. these", "keratinocyte lipid transporter. these lipids", "lipid transporter. these lipids form", "transporter. these lipids form extracellular", "these lipids form extracellular lipid", "lipids form extracellular lipid layers", "form extracellular lipid layers in", "extracellular lipid layers in the", "lipid layers in the stratum", "layers in the stratum corneum", "in the stratum corneum of", "the stratum corneum of the", "stratum corneum of the epidermis", "of the epidermis essential", "the epidermis essential for", "epidermis essential for skin", "essential for skin barrier function.", "for skin barrier function. defects", "skin barrier function. defects in", "barrier function. defects in abca12", "function. defects in abca12 results", "defects in abca12 results in", "in abca12 results in the", "abca12 results in the loss", "results in the loss of", "in the loss of the", "the loss of the skin", "loss of the skin lipid", "of the skin lipid barrier", "skin lipid barrier leading", "lipid barrier leading to", "barrier leading to autosomal", "leading to autosomal recessive congenital", "to autosomal recessive congenital ichthyosis", "autosomal recessive congenital ichthyosis 4b", "congenital ichthyosis 4b arci4b", "4b arci4b mim:242500", "arci4b mim:242500 aka", "mim:242500 aka harlequin ichthyosis", "242500 aka harlequin ichthyosis", "aka harlequin ichthyosis hi", "harlequin ichthyosis hi .", "ichthyosis hi . arci4b", "hi . arci4b shows the", ". arci4b shows the most", "arci4b shows the most severe", "shows the most severe phenotype", "the most severe phenotype of", "most severe phenotype of the", "severe phenotype of the congenital", "phenotype of the congenital ichthyoses", "the congenital ichthyoses with", "congenital ichthyoses with newborns", "ichthyoses with newborns having", "with newborns having a thick", "newborns having a thick covering", "having a thick covering of", "a thick covering of armour", "thick covering of armour like", "covering of armour like scales.", "of armour like scales. the", "armour like 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"record_id": "GLY_000594_1_1778", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "5683177", "r hsa", "hsa 5683177", "r hsa 5683177" ] }, { "record_id": "GLY_000594_1_1778", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abcc8", "abcc8 can", "can cause", "cause hypo", "and hyper", "hyper glycemias", "defective abcc8 can", "abcc8 can cause", "can cause hypo", "hypo and", "and hyper glycemias", "defective abcc8 can cause", "abcc8 can cause hypo", "cause hypo and", "hypo and hyper", "defective abcc8 can cause hypo", "can cause hypo and", "cause hypo and hyper", "hypo and hyper glycemias", "atp binding", "binding cassette", "cassette sub", "sub family", "family c", "c member", "member 8", "is a", "a subunit", "subunit of", "of the", "the beta", "beta cell", "cell atp", "atp sensitive", "sensitive potassium", "potassium channel", "katp .", ". katp", "katp channels", "channels play", "play 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"storage granules. defects in abcc8", "granules. defects in abcc8 can", "defects in abcc8 can cause", "in abcc8 can cause dysregulation", "abcc8 can cause dysregulation of", "can cause dysregulation of insulin", "cause dysregulation of insulin secretion", "dysregulation of insulin secretion resulting", "of insulin secretion resulting in", "insulin secretion resulting in hyperglycemias", "secretion resulting in hyperglycemias or", "resulting in hyperglycemias or hypoglycemias.", "in hyperglycemias or hypoglycemias. specific", "hyperglycemias or hypoglycemias. specific phenotypes", "or hypoglycemias. specific phenotypes observed", "hypoglycemias. specific phenotypes observed are", "specific phenotypes observed are noninsulin", "phenotypes observed are noninsulin dependent", "observed are noninsulin dependent diabetes", "are noninsulin dependent diabetes mellitus", "dependent diabetes mellitus niddm", "mellitus niddm mim:125853", "mim:125853 permanent neonatal", "125853 permanent 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5683371", "r hsa 5683371" ] }, { "record_id": "GLY_000594_1_1779", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective abcb6", "abcb6 causes", "causes mcopcb7", "defective abcb6 causes", "abcb6 causes mcopcb7", "defective abcb6 causes mcopcb7", "atp binding", "binding cassette", "cassette sub", "sub family", "family b", "b member", "member 6", "uniquely located", "located on", "on the", "the outer", "outer mitochondrial", "mitochondrial membrane", "membrane in", "in homodimeric", "homodimeric form", "plays a", "a crucial", "crucial role", "role in", "in haem", "haem synthesis", "synthesis by", "by mediating", "mediating porphyrin", "porphyrin uptake", "uptake into", "into the", "the mitochondria.", "mitochondria. defects", "defects in", "in abcb6", "abcb6 can", "can cause", "cause isolated", "isolated colobomatous", "colobomatous microphthalmia", "microphthalmia 7", "a developmental", "developmental defect", "defect of", "of the", "the eye", 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located at the peptidyl", "located at the peptidyl transferase", "at the peptidyl transferase center", "the peptidyl transferase center of", "peptidyl transferase center of the", "transferase center of the large", "center of the large subunit.", "of the large subunit. here", "the large subunit. here the", "large subunit. here the modified", "subunit. here the modified residues", "here the modified residues play", "the modified residues play a", "modified residues play a role", "residues play a role in", "play a role in interaction", "a role in interaction with", "role in interaction with the", "in interaction with the aminoacyl", "interaction with the aminoacyl site", "with the aminoacyl site of", "the aminoacyl site of trna.", "aminoacyl site of trna. knockouts", "site of trna. knockouts of", "of trna. knockouts of tfb1m", "trna. knockouts of tfb1m and", "knockouts of tfb1m and nsun4", "of tfb1m and nsun4 are", "tfb1m and nsun4 are lethal", "and nsun4 are lethal in", "nsun4 are lethal in mice", "are lethal in mice and", "lethal in mice and mutations", "in mice and mutations in", "mice and mutations in tfb1m", "and mutations in tfb1m may", "mutations in tfb1m may be", "in tfb1m may be related", "tfb1m may be related to", "may be related to aminoglycoside", "be related to aminoglycoside induced", "related to aminoglycoside induced deafness", "aminoglycoside induced deafness reviewed", "induced deafness reviewed in", "deafness reviewed in van" ] }, { "record_id": "GLY_000594_1_1788", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "6798163", "r hsa", "hsa 6798163", "r hsa 6798163" ] }, { "record_id": "GLY_000594_1_1788", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "choline catabolism", "choline is", "is an", "an essential", "essential water", "water soluble", "soluble nutrient", "nutrient in", "in humans", "serving as", "as a", "a precursor", "precursor of", "of 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water", "essential water soluble", "water soluble nutrient", "soluble nutrient in", "nutrient in humans", "humans serving", "serving as a", "as a precursor", "a precursor of", "precursor of phospholipids", "of phospholipids and", "phospholipids and the", "and the neurotransmitter", "the neurotransmitter acetylcholine.", "neurotransmitter acetylcholine. it", "acetylcholine. it is", "it is often", "is often associated", "often associated with", "associated with b", "with b vitamins", "b vitamins based", "vitamins based on", "based on its", "on its chemical", "its chemical structure", "chemical structure but", "structure but it", "but it isn't", "it isn't an", "isn't an official", "an official b", "official b vitamin.", "b vitamin. its", "vitamin. its oxidation", "its oxidation to", "oxidation to betaine", "to betaine provides", "betaine provides a", "provides a link", "a link to", "link to folate", "to folate dependent", "dependent one", "one carbon metabolism", "carbon metabolism 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"phospholipids and the neurotransmitter acetylcholine.", "and the neurotransmitter acetylcholine. it", "the neurotransmitter acetylcholine. it is", "neurotransmitter acetylcholine. it is often", "acetylcholine. it is often associated", "it is often associated with", "is often associated with b", "often associated with b vitamins", "associated with b vitamins based", "with b vitamins based on", "b vitamins based on its", "vitamins based on its chemical", "based on its chemical structure", "on its chemical structure but", "its chemical structure but it", "chemical structure but it isn't", "structure but it isn't an", "but it isn't an official", "it isn't an official b", "isn't an official b vitamin.", "an official b vitamin. its", "official b vitamin. its oxidation", "b vitamin. its oxidation to", "vitamin. its oxidation to betaine", "its oxidation to betaine provides", "oxidation to betaine provides a", "to betaine provides a link", "betaine provides a link to", "provides a link to 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the gamma", "2013 . the gamma carboxylation", ". the gamma carboxylation reactions", "gamma carboxylation reactions annotated", "carboxylation reactions annotated elsewhere", "reactions annotated elsewhere in", "annotated elsewhere in reactome as", "elsewhere in reactome as a", "in reactome as a part", "reactome as a part of", "as a part of protein", "a part of protein metabolism", "of protein metabolism convert", "protein metabolism convert mk4", "metabolism convert mk4 to", "convert mk4 to its epoxide", "mk4 to its epoxide form", "its epoxide form which", "epoxide form which is", "form which is inactive", "which is inactive as a", "is inactive as a cofactor.", "inactive as a cofactor. two", "as a cofactor. two related", "a cofactor. two related enzymes", "two related enzymes vkorc1", "related enzymes vkorc1 and", "enzymes vkorc1 and vkorcl1", "vkorc1 and vkorcl1 can", "and vkorcl1 can each", "vkorcl1 can each catalyze", "can each catalyze the reduction", "each catalyze the reduction of", "catalyze the reduction of mk4", "the reduction of mk4 epoxide", "reduction of mk4 epoxide to", "of mk4 epoxide to active", "mk4 epoxide to active mk4.", "epoxide to active mk4. vkorc1", "to active mk4. vkorc1 activity", "active mk4. vkorc1 activity is", "mk4. vkorc1 activity is essential", "vkorc1 activity is essential for", "activity is essential for normal", "is essential for normal operation", "essential for normal operation of", "for normal operation of the", "normal operation of the blood", "operation of the blood clotting", "of the blood clotting cascade", "the blood clotting cascade and", "blood clotting cascade and for", "clotting cascade and for osteocalcin", "cascade and for osteocalcin function", "for osteocalcin function ferron", "osteocalcin function ferron et", "function ferron et al.", "ferron et al. 2015 .", "et al. 2015 . a", "al. 2015 . a physiological", "2015 . a physiological function", ". a physiological function for", "a physiological function for vkorcl1", 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events corda", "developmental events corda et", "events corda et al.", "corda et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1791", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "68881", "r hsa", "hsa 68881", "r hsa 68881" ] }, { "record_id": "GLY_000594_1_1791", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitotic metaphase/anaphase", "metaphase/anaphase transition", "mitotic metaphase/anaphase transition", "the metaphase", "metaphase to", "to anaphase", "anaphase transition", "transition during", "during mitosis", "mitosis is", "is triggered", "triggered by", "by the", "the destruction", "destruction of", "of mitotic", "mitotic cyclins.", "the metaphase to", "metaphase to anaphase", "to anaphase transition", "anaphase transition during", "transition during mitosis", "during mitosis is", "mitosis is triggered", "is triggered by", "triggered by the", "by the destruction", "the destruction 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"hsa 71737", "r hsa 71737" ] }, { "record_id": "GLY_000594_1_1792", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pyrophosphate hydrolysis", "many biosynthetic", "biosynthetic reactions", "reactions are", "are coupled", "coupled to", "to the", "the cleavage", "cleavage of", "of atp", "atp to", "to yield", "yield amp", "amp and", "and pyrophosphate.", "these reactions", "are typically", "typically freely", "freely reversible", "reversible when", "when carried", "carried out", "out with", "with purified", "purified substrates", "substrates and", "and enzymes", "enzymes in", "in vitro.", "in vivo", "the pyrophosphate", "pyrophosphate is", "is rapdily", "rapdily and", "and essentially", "essentially irreversibly", "irreversibly hydrolyzed", "hydrolyzed by", "by a", "a ubiquitous", "ubiquitous inorganic", "inorganic pyrophosphatase.", "pyrophosphatase. this", "this hydrolysis", "hydrolysis has", "has the", "the effect", "effect of", "of pulling", 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              pyrophosphatase", ".
              pyrophosphatase activity", "activity has", "has likewise", "likewise been", "been shown", "shown for", "for lhpp", "phospholysine phosphohistidine", "phosphohistidine inorganic", "inorganic pyrophosphate", "pyrophosphate phosphatase", "phosphatase .", ". recent", "recent work", "work indicates", "indicates that", "that lhpp", "lhpp acts", "acts as", "as well", "well to", "to dephosphorylate", "dephosphorylate phosphohistidine", "phosphohistidine residues", "that variants", "variants of", "of it", "it may", "may be", "be associated", "associated with", "with suceptibilty", "suceptibilty to", "to depression", "and that", "that it", "be a", "a tumor", "tumor suppressor", "reviewed in", "in gohla", "gohla 2019", "although without", "without the", "the molecular", "molecular detail", "detail needed", "needed for", "for a", "a reactome", "reactome annotation.", "many biosynthetic reactions", "biosynthetic reactions are", "reactions are coupled", "are coupled to", "coupled to the", "to the cleavage", "the cleavage of", "cleavage of atp", "of atp to", "atp to yield", "to yield amp", "yield amp and", "amp and pyrophosphate.", "pyrophosphate. these", "these reactions are", "reactions are typically", "are typically freely", "typically freely reversible", "freely reversible when", "reversible when carried", "when carried out", "carried out with", "out with purified", "with purified substrates", "purified substrates and", "substrates and enzymes", "and enzymes in", "enzymes in vitro.", "vitro. in", "vivo however", "however the", "the pyrophosphate is", "pyrophosphate is rapdily", "is rapdily and", "rapdily and essentially", "and essentially irreversibly", "essentially irreversibly hydrolyzed", "irreversibly hydrolyzed by", "hydrolyzed by a", "by a ubiquitous", "a ubiquitous inorganic", "ubiquitous inorganic pyrophosphatase.", "inorganic pyrophosphatase. this", "pyrophosphatase. this hydrolysis", "this hydrolysis has", "hydrolysis has the", "has the effect", "the effect of", "effect of pulling", "of pulling the", "pulling the first", "the first reaction", "first reaction strongly", "reaction strongly in", "strongly in the", "in the direction", "the direction of", "direction of biosynthesis", "biosynthesis at", "at the expense", "the expense of", "expense of two", "of two high", "two high energy", "high energy phosphate", "energy phosphate bonds.", "phosphate bonds. studies", "bonds. studies of", "studies of human", "of human cells", "human cells have", "cells have identified", "have identified two", "identified two forms", "two forms of", "forms of the", "of the enzyme", "enzyme one", "one localized to", "localized to the", "to the cytosol", "the cytosol and", "cytosol and the", "and the other", "the other to", "other to the", "to the mitochondrial", "the mitochondrial matrix", "matrix raja", "raja et al.", "et al. 1981", "al. 1981 .
              pyrophosphatase", "1981 .
              pyrophosphatase activity", ".
              pyrophosphatase activity has", "activity has likewise", "has likewise been", "likewise been shown", "been shown for", "shown for lhpp", "lhpp phospholysine", "phospholysine phosphohistidine inorganic", "phosphohistidine inorganic pyrophosphate", "inorganic pyrophosphate phosphatase", "pyrophosphate phosphatase .", "phosphatase . recent", ". recent work", "recent work indicates", "work indicates that", "indicates that lhpp", "that lhpp acts", "lhpp acts as", "acts as well", "as well to", "well to dephosphorylate", "to dephosphorylate phosphohistidine", "dephosphorylate phosphohistidine residues", "residues that", "that variants of", "variants of it", "of it may", "it may be", "may be associated", "be associated with", "associated with suceptibilty", "with suceptibilty to", "suceptibilty to depression", "depression and", "and that it", "that it may", "may be a", "be a tumor", "a tumor suppressor", "suppressor reviewed", "reviewed in gohla", "in gohla 2019", "although without the", "without the molecular", "the molecular detail", "molecular detail needed", "detail needed for", "needed for a", "for a reactome", "a reactome annotation.", "many biosynthetic reactions are", "biosynthetic reactions are coupled", "reactions are coupled to", "are coupled to the", "coupled to the cleavage", "to the cleavage of", "the cleavage of atp", "cleavage of atp to", "of atp to yield", "atp to yield amp", "to yield amp and", "yield amp and pyrophosphate.", "and pyrophosphate. these", "pyrophosphate. these reactions", "these reactions are typically", "reactions are typically freely", "are typically freely reversible", "typically freely reversible when", "freely reversible when carried", "reversible when carried out", "when carried out with", "carried out with purified", "out with purified substrates", "with purified substrates and", "purified substrates and enzymes", "substrates and enzymes in", "and enzymes in vitro.", "in vitro. in", "vitro. in vivo", "in vivo however", "however the pyrophosphate", "the pyrophosphate is rapdily", "pyrophosphate is rapdily and", "is rapdily and essentially", "rapdily and essentially irreversibly", "and essentially irreversibly hydrolyzed", "essentially irreversibly hydrolyzed by", "irreversibly hydrolyzed by a", "hydrolyzed by a ubiquitous", "by a ubiquitous inorganic", "a ubiquitous inorganic pyrophosphatase.", "ubiquitous inorganic pyrophosphatase. this", "inorganic pyrophosphatase. this hydrolysis", "pyrophosphatase. this hydrolysis has", "this hydrolysis has the", "hydrolysis has the effect", "has the effect of", "the effect of pulling", "effect of pulling the", "of pulling the first", "pulling the first reaction", "the first reaction strongly", "first reaction strongly in", "reaction strongly in the", "strongly in the direction", "in the direction of", "the direction of biosynthesis", "of biosynthesis at", "biosynthesis at the", "at the expense of", "the expense of two", "expense of two high", "of two high energy", "two high energy phosphate", "high energy phosphate bonds.", "energy phosphate bonds. studies", "phosphate bonds. studies of", "bonds. studies of human", "studies of human cells", "of human cells have", "human cells have identified", "cells have identified two", "have identified two forms", "identified two forms of", "two forms of the", "forms of the enzyme", "the enzyme one", "enzyme one localized", "one localized to the", "localized to the cytosol", "to the cytosol and", "the cytosol and the", "cytosol and the other", "and the other to", "the other to the", "other to the mitochondrial", "to the mitochondrial matrix", "mitochondrial matrix raja", "matrix raja et", "raja et al. 1981", "et al. 1981 .
              pyrophosphatase", "al. 1981 .
              pyrophosphatase activity", "1981 .
              pyrophosphatase activity has", ".
              pyrophosphatase activity has likewise", "activity has likewise been", "has likewise been shown", "likewise been shown for", "been shown for lhpp", "for lhpp phospholysine", "lhpp phospholysine phosphohistidine", "phospholysine phosphohistidine inorganic pyrophosphate", "phosphohistidine inorganic pyrophosphate phosphatase", "inorganic pyrophosphate phosphatase .", "pyrophosphate phosphatase . recent", "phosphatase . recent work", ". recent work indicates", "recent work indicates that", "work indicates that lhpp", "indicates that lhpp acts", "that lhpp acts as", "lhpp acts as well", "acts as well to", "as well to dephosphorylate", "well to dephosphorylate phosphohistidine", "to dephosphorylate phosphohistidine residues", "phosphohistidine residues that", "residues that variants", "that variants of it", "variants of it may", "of it may be", "it may be associated", "may be associated with", "be associated with suceptibilty", "associated with suceptibilty to", "with suceptibilty to depression", "to depression and", "depression and that", "and that it may", "that it may be", "it may be a", "may be a tumor", "be a tumor suppressor", "tumor suppressor reviewed", "suppressor reviewed in", "reviewed in gohla 2019", "2019 although", "although without the molecular", "without the molecular detail", "the molecular detail needed", "molecular detail needed for", "detail needed for a", "needed for a reactome", "for a reactome annotation.", "many biosynthetic reactions are coupled", "biosynthetic reactions are coupled to", "reactions are coupled to the", "are coupled to the cleavage", "coupled to the cleavage of", "to the cleavage of atp", "the cleavage of atp to", "cleavage of atp to yield", "of atp to yield amp", "atp to yield amp and", "to yield amp and pyrophosphate.", "amp and pyrophosphate. these", "and pyrophosphate. these reactions", "pyrophosphate. these reactions are", "these reactions are typically freely", "reactions are typically freely reversible", "are typically freely reversible when", "typically freely reversible when carried", "freely reversible when carried out", "reversible when carried out with", "when carried out with purified", "carried out with purified substrates", "out with purified substrates and", "with purified substrates and enzymes", "purified substrates and enzymes in", "substrates and enzymes in vitro.", "enzymes in vitro. in", "in vitro. in vivo", "vivo however the", "however the pyrophosphate is", "the pyrophosphate is rapdily and", "pyrophosphate is rapdily and essentially", "is rapdily and essentially irreversibly", "rapdily and essentially irreversibly hydrolyzed", "and essentially irreversibly hydrolyzed by", "essentially irreversibly hydrolyzed by a", "irreversibly hydrolyzed by a ubiquitous", "hydrolyzed by a ubiquitous inorganic", "by a ubiquitous inorganic pyrophosphatase.", "a ubiquitous inorganic pyrophosphatase. this", "ubiquitous inorganic pyrophosphatase. this hydrolysis", "inorganic pyrophosphatase. this hydrolysis has", "pyrophosphatase. this hydrolysis has the", "this hydrolysis has the effect", "hydrolysis has the effect of", "has the effect of pulling", "the effect of pulling the", "effect of pulling the first", "of pulling the first reaction", "pulling the first reaction strongly", "the first reaction strongly in", "first reaction strongly in the", "reaction strongly in the direction", "strongly in the direction of", "in the direction of biosynthesis", "direction of biosynthesis at", "of biosynthesis at the", "biosynthesis at the expense", "at the expense of two", "the expense of two high", "expense of two high energy", "of two high energy phosphate", "two high energy phosphate bonds.", "high energy phosphate bonds. studies", "energy phosphate bonds. studies of", "phosphate bonds. studies of human", "bonds. studies of human cells", "studies of human cells have", "of human cells have identified", "human cells have identified two", "cells have identified two forms", "have identified two forms of", "identified two forms of the", "two forms of the enzyme", "of the enzyme one", "the enzyme one localized", "enzyme one localized to", "one localized to the cytosol", "localized to the cytosol and", "to the cytosol and the", "the cytosol and the other", "cytosol and the other to", "and the other to the", "the other to the mitochondrial", "other to the mitochondrial matrix", "the mitochondrial matrix raja", "mitochondrial matrix raja et", "matrix raja et al.", "raja et al. 1981 .
              pyrophosphatase", "et al. 1981 .
              pyrophosphatase activity", "al. 1981 .
              pyrophosphatase activity has", "1981 .
              pyrophosphatase activity has likewise", ".
              pyrophosphatase activity has likewise been", "activity has likewise been shown", "has likewise been shown for", "likewise been shown for lhpp", "shown for lhpp phospholysine", "for lhpp phospholysine phosphohistidine", "lhpp phospholysine phosphohistidine inorganic", "phospholysine phosphohistidine inorganic pyrophosphate phosphatase", "phosphohistidine inorganic pyrophosphate phosphatase .", "inorganic pyrophosphate phosphatase . recent", "pyrophosphate phosphatase . recent work", "phosphatase . recent work indicates", ". recent work indicates that", "recent work indicates that lhpp", "work indicates that lhpp acts", "indicates that lhpp acts as", "that lhpp acts as well", "lhpp acts as well to", "acts as well to dephosphorylate", "as well to dephosphorylate phosphohistidine", "well to dephosphorylate phosphohistidine residues", "dephosphorylate phosphohistidine residues that", "phosphohistidine residues that variants", "residues that variants of", "that variants of it may", "variants of it may be", "of it may be associated", "it may be associated with", "may be associated with suceptibilty", "be associated with suceptibilty to", "associated with suceptibilty to depression", "suceptibilty to depression and", "to depression and that", "depression and that it", "and that it may be", "that it may be a", "it may be a tumor", "may be a tumor suppressor", "a tumor suppressor reviewed", "tumor suppressor reviewed in", "suppressor reviewed in gohla", "gohla 2019 although", "2019 although without", "although without the molecular detail", "without the molecular detail needed", "the molecular detail needed for", "molecular detail needed for a", "detail needed for a reactome", "needed for a reactome annotation." ] }, { "record_id": "GLY_000594_1_1793", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "72200", "r hsa", "hsa 72200", "r hsa 72200" ] }, { "record_id": "GLY_000594_1_1793", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mrna editing:", "editing: c", "c to", "to u", "u conversion", "mrna editing: c", "editing: c to", "c to u", "to u conversion", "mrna editing: c to", "editing: c to u", "c to u conversion", "mrna editing: c to u", "editing: c to u conversion", "the best", "best characterized", "characterized case", "case of", "of c", "u editing", "editing is", "is in", "in the", "the intestinal", "intestinal apolipoprotein", "apolipoprotein b", "b transcript", "where the", "the editing", "editing event", "event creates", "creates a", "a premature", "premature translation", "translation stop", "stop codon", "codon and", "and consequently", "consequently leads", "leads to", "to a", "a shorter", "shorter form", "form of", "of the", "the protein.", "protein. in", "the liver", "is important", "important in", "the expression", "expression of", "of specific", "specific isoforms", "isoforms of", "the apolipoprotein", "b enzyme.", "enzyme. apob", "apob mrna", "is a", "a posttranscriptional", "nuclear process", "process that", "that can", "can be", "be initiated", "initiated after", "after splicing", "at the", "the time", "time of", "of polyadenylation", "polyadenylation and", "and is", "is completed", "completed by", "by the", "time pre", "pre mrna", "mrna matures", "matures fully", "reviewed by", "by blanc", "blanc and", "and davidson", "2003 .
              this", ".
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monophosphates eg. ump", "monophosphates eg. ump for", "eg. ump for udp sugars", "ump for udp sugars .", "for udp sugars . owing", "udp sugars . owing to", "sugars . owing to their", ". owing to their function", "to their function nsts", "their function nsts are", "function nsts are primarily", "nsts are primarily located on", "are primarily located on golgi", "primarily located on golgi and", "located on golgi and er", "on golgi and er membranes", "and er membranes he", "er membranes he l", "membranes he l et", "l et al 2009", "al 2009 handford", "2009 handford m et", "m et al 2006", "al 2006 ishida", "2006 ishida n and", "ishida n and kawakita m", "and kawakita m 2004", "kawakita m 2004 ." ] }, { "record_id": "GLY_000594_1_1795", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "73933", "r hsa", "hsa 73933", "r hsa 73933" ] }, { "record_id": "GLY_000594_1_1795", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "resolution of", "of abasic", "abasic sites", "ap sites", "resolution of abasic", "of abasic sites", "sites ap", "resolution of abasic sites", "abasic sites ap", "sites ap sites", "of abasic sites ap", "abasic sites ap sites", "of ap", "sites can", "can occur", "occur through", "through the", "the single", "single nucleotide", "nucleotide replacement", "replacement pathway", "pathway or", "or through", "the multiple", "multiple nucleotide", "nucleotide patch", "patch replacement", "also known", "known as", "as the", "the long", "long patch", "patch base", "base excision", "excision repair", "ber .", ". except", "except for", "for the", "the apex1", "apex1 independent", "independent resolution", "sites via", "via single", "nucleotide base", "repair mediated", "mediated by", "by neil1", "neil1 or", "or neil2", "wiederhold et", "et al.", "al. 2004", "das et", "al. 2006", "nucleotide and", "and multiple", "replacement pathways", "pathways are", "are both", "both initiated", "initiated by", "by apex1", "apex1 mediated", "mediated displacement", "displacement of", "of dna", "dna glycosylases", "glycosylases and", "and cleavage", "cleavage of", "of the", "the damaged", "damaged dna", "dna strand", "strand by", "apex1 immediately", "immediately 5'", "5' to", "to the", "the ap", "ap site", "wilson et", "al. 1995", "bennett et", "al. 1997", "masuda et", "al. 1998", "1998 .", ". the", "the ber", "ber proceeds", "proceeds via", "via the", "replacement when", "when the", "deoxyribose residue", "residue at", "at the", "the 5'", "5' end", "end of", "apex1 created", "created single", "single strand", "strand break", "can be", "be removed", "removed by", "by the", "5' exonuclease", "exonuclease activity", "activity of", "dna polymerase", "polymerase beta", "1997 .", ". polb", "polb fills", "fills the", "the created", "nucleotide gap", "gap by", "by adding", "adding a", "a nucleotide", "nucleotide complementary", "complementary to", "the undamaged", "undamaged dna", "strand to", "the 3'", "3' end", "the ssb.", "ssb. the", "the ssb", "ssb is", "is subsequently", "subsequently ligated", "ligated by", "by dna", "dna ligase", "ligase iii", "in complex", "complex with", "with xrcc1", "is recruited", "recruited to", "ber site", "site by", "by an", "an xrcc1", "xrcc1 mediated", "mediated interaction", "interaction with", "with polb", "kubota et", "al. 1996", "1996 .", ". ber", "pathway when", "ap residue", "created ssb", "ssb undergoes", "undergoes oxidation", "oxidation related", "related damage", "and cannot", "cannot be", "be cleaved", "cleaved by", "by polb", "klungland and", "and lindahl", "lindahl 1997", ". long", "patch ber", "ber can", "be completed", "completed by", "polb mediated", "mediated dna", "strand displacement", "displacement synthesis", "synthesis in", "in the", "the presence", "presence of", "of parp1", "parp1 or", "or parp2", "fen1 and", "and dna", "ligase i", "prasad et", "al. 2001", "2001 .", ". when", "the pcna", "pcna containing", "containing replication", "replication complex", "complex is", "is available", "as is", "is the", "the case", "case with", "with cells", "cells in", "in s", "s phase", "phase of", "the cell", "cell cycle", "synthesis is", "is catalyzed", "catalyzed by", "polymerase delta", "or dna", "polymerase epsilon", "of pcna", "and lig1", "dianova et", ". it", "it is", "is likely", "likely that", "that the", "the 9", "9 1", "1 1", "1 repair", "repair complex", "complex composed", "composed of", "of hus1", "rad1 and", "and rad9", "rad9 interacts", "interacts with", "with and", "and coordinates", "coordinates components", "components of", "of ber", "but the", "the exact", "exact mechanism", "mechanism and", "and timing", "timing have", "have not", "not been", "been elucidated", "wang et", "smirnova et", "al. 2005", "guan et", "al. 2007", "balakrishnan et", "al. 2009", "2009 .", "resolution of ap", "of ap sites", "ap sites can", "sites can occur", "can occur through", "occur through the", "through the single", "the single nucleotide", "single nucleotide replacement", "nucleotide replacement pathway", "replacement pathway or", "pathway or through", "or through the", "through the multiple", "the multiple nucleotide", "multiple nucleotide patch", "nucleotide patch replacement", "patch replacement pathway", "pathway also", "also known as", "known as the", "as the long", "the long patch", "long patch base", "patch base excision", "base excision repair", "repair ber", "ber . except", ". except for", "except for the", "for the apex1", "the apex1 independent", "apex1 independent resolution", "independent resolution of", "ap sites via", "sites via single", "via single nucleotide", "single nucleotide base", "nucleotide base excision", "excision repair mediated", "repair mediated by", "mediated by neil1", "by neil1 or", "neil1 or neil2", "neil2 wiederhold", "wiederhold et al.", "et al. 2004", "2004 das", "das et al.", "et al. 2006", "single nucleotide and", "nucleotide and multiple", "and multiple nucleotide", "patch replacement pathways", "replacement pathways are", "pathways are both", "are both initiated", "both initiated by", "initiated by apex1", "by apex1 mediated", "apex1 mediated displacement", "mediated displacement of", "displacement of dna", "of dna glycosylases", "dna glycosylases and", "glycosylases and cleavage", "and cleavage of", "cleavage of the", "of the damaged", "the damaged dna", "damaged dna strand", "dna strand by", "strand by apex1", "by apex1 immediately", "apex1 immediately 5'", "immediately 5' to", "5' to the", "to the ap", "the ap site", "site wilson", "wilson et al.", "et al. 1995", "1995 bennett", "bennett et al.", "et al. 1997", "1997 masuda", "masuda et al.", "et al. 1998", "al. 1998 .", "1998 . the", ". the ber", "the ber proceeds", "ber proceeds via", "proceeds via the", "via the single", "nucleotide replacement when", "replacement when the", "when the ap", "ap apurinic/apyrimidinic", "apurinic/apyrimidinic deoxyribose", "deoxyribose residue at", "residue at the", "at the 5'", "the 5' end", "5' end of", "end of the", "of the apex1", "the apex1 created", "apex1 created single", "created single strand", "single strand break", "break ssb", "5'drp can", "can be removed", "be removed by", "removed by the", "by the 5'", "the 5' exonuclease", "5' exonuclease activity", "exonuclease activity of", "activity of dna", "of dna polymerase", "dna polymerase beta", "beta polb", "al. 1997 .", "1997 . polb", ". polb fills", "polb fills the", "fills the created", "the created single", "created single nucleotide", "single nucleotide gap", "nucleotide gap by", "gap by adding", "by adding a", "adding a nucleotide", "a nucleotide complementary", "nucleotide complementary to", "complementary to the", "to the undamaged", "the undamaged dna", "undamaged dna strand", "dna strand to", "strand to the", "to the 3'", "the 3' end", "3' end of", "of the ssb.", "the ssb. the", "ssb. the ssb", "the ssb is", "ssb is subsequently", "is subsequently ligated", "subsequently ligated by", "ligated by dna", "by dna ligase", "dna ligase iii", "iii lig3", "lig3 which", "which in", "in complex with", "complex with xrcc1", "xrcc1 is", "is recruited to", "recruited to the", "to the ber", "the ber site", "ber site by", "site by an", "by an xrcc1", "an xrcc1 mediated", "xrcc1 mediated interaction", "mediated interaction with", "interaction with polb", "polb kubota", "kubota et al.", "et al. 1996", "al. 1996 .", "1996 . ber", ". ber proceeds", "via the multiple", "replacement pathway when", "pathway when the", "the ap residue", "ap residue at", "apex1 created ssb", "created ssb undergoes", "ssb undergoes oxidation", "undergoes oxidation related", "oxidation related damage", "damage 5'ddrp", "5'ddrp and", "and cannot be", "cannot be cleaved", "be cleaved by", "cleaved by polb", "polb klungland", "klungland and lindahl", "and lindahl 1997", "lindahl 1997 .", "1997 . long", ". long patch", "long patch ber", "patch ber can", "ber can be", "can be completed", "be completed by", "completed by polb", "by polb mediated", "polb mediated dna", "mediated dna strand", "dna strand displacement", "strand displacement synthesis", "displacement synthesis in", "synthesis in the", "in the presence", "the presence of", "presence of parp1", "of parp1 or", "parp1 or parp2", "parp2 fen1", "fen1 and dna", "and dna ligase", "dna ligase i", "i lig1", "prasad et al.", "et al. 2001", "al. 2001 .", "2001 . when", ". when the", "when the pcna", "the pcna containing", "pcna containing replication", "containing replication complex", "replication complex is", "complex is available", "available as", "as is the", "is the case", "the case with", "case with cells", "with cells in", "cells in s", "in s phase", "s phase of", "phase of the", "of the cell", "the cell cycle", "cycle dna", "displacement synthesis is", "synthesis is catalyzed", "is catalyzed by", "catalyzed by dna", "by dna polymerase", "dna polymerase delta", "delta pold", "pold or", "or dna polymerase", "dna polymerase epsilon", "epsilon pole", "pole complexes", "complexes in", "presence of pcna", "pcna rpa", "rpa rfc", "rfc apex1", "apex1 fen1", "fen1 and lig1", "lig1 klungland", "1997 dianova", "dianova et al.", "2001 . it", ". it is", "it is likely", "is likely that", "likely that the", "that the 9", "the 9 1", "9 1 1", "1 1 repair", "1 repair complex", "repair complex composed", "complex composed of", "composed of hus1", "hus1 rad1", "rad1 and rad9", "and rad9 interacts", "rad9 interacts with", "interacts with and", "with and coordinates", "and coordinates components", "coordinates components of", "components of ber", "ber but", "but the exact", "the exact mechanism", "exact mechanism and", "mechanism and timing", "and timing have", "timing have not", "have not been", "not been elucidated", "elucidated wang", "wang et al.", "2004 smirnova", "smirnova et al.", "et al. 2005", "2005 guan", "guan et al.", "et al. 2007", "2007 balakrishnan", "balakrishnan et al.", "et al. 2009", "al. 2009 .", "resolution of ap sites", "of ap sites can", "ap sites can occur", "sites can occur through", "can occur through the", "occur through the single", "through the single nucleotide", "the single nucleotide replacement", "single nucleotide replacement pathway", "nucleotide replacement pathway or", "replacement pathway or through", "pathway or through the", "or through the multiple", "through the multiple nucleotide", "the multiple nucleotide patch", "multiple nucleotide patch replacement", "nucleotide patch replacement pathway", "replacement pathway also", "pathway also known", "also known as the", "known as the long", "as the long patch", "the long patch base", "long patch base excision", "patch base excision repair", "excision repair ber", "repair ber .", "ber . except for", ". except for the", "except for the apex1", "for the apex1 independent", "the apex1 independent resolution", "apex1 independent resolution of", "independent resolution of ap", "of ap sites via", "ap sites via single", "sites via single nucleotide", "via single nucleotide base", "single nucleotide base excision", "nucleotide base excision repair", "base excision repair mediated", "excision repair mediated by", "repair mediated by neil1", "mediated by neil1 or", "by neil1 or neil2", "or neil2 wiederhold", "neil2 wiederhold et", "wiederhold et al. 2004", "al. 2004 das", "2004 das et", "das et al. 2006", "2006 single", "single nucleotide and multiple", "nucleotide and multiple nucleotide", "and multiple nucleotide patch", "nucleotide patch replacement pathways", "patch replacement pathways are", "replacement pathways are both", "pathways are both initiated", "are both initiated by", "both initiated by apex1", "initiated by apex1 mediated", "by apex1 mediated displacement", "apex1 mediated displacement of", "mediated displacement of dna", "displacement of dna glycosylases", "of dna glycosylases and", "dna glycosylases and cleavage", "glycosylases and cleavage of", "and cleavage of the", "cleavage of the damaged", "of the damaged dna", "the damaged dna strand", "damaged dna strand by", "dna strand by apex1", "strand by apex1 immediately", "by apex1 immediately 5'", "apex1 immediately 5' to", "immediately 5' to the", "5' to the ap", "to the ap site", "ap site wilson", "site wilson et", "wilson et al. 1995", "al. 1995 bennett", "1995 bennett et", "bennett et al. 1997", "al. 1997 masuda", "1997 masuda et", "masuda et al. 1998", "et al. 1998 .", "al. 1998 . the", "1998 . the ber", ". the ber proceeds", "the ber proceeds via", "ber proceeds via the", "proceeds via the single", "via the single nucleotide", "single nucleotide replacement when", "nucleotide replacement when the", "replacement when the ap", "the ap apurinic/apyrimidinic", "apurinic/apyrimidinic deoxyribose residue", "deoxyribose residue at the", "residue at the 5'", "at the 5' end", "the 5' end of", "5' end of the", "end of the apex1", "of the apex1 created", "the apex1 created single", "apex1 created single strand", "created single strand break", "strand break ssb", "ssb 5'drp", "5'drp can be", "can be removed by", "be removed by the", "removed by the 5'", "by the 5' exonuclease", "the 5' exonuclease activity", "5' exonuclease activity of", "exonuclease activity of dna", "activity of dna polymerase", "of dna polymerase beta", "polymerase beta polb", "polb bennett", "et al. 1997 .", "al. 1997 . polb", "1997 . polb fills", ". polb fills the", "polb fills the created", "fills the created single", "the created single nucleotide", "created single nucleotide gap", "single nucleotide gap by", "nucleotide gap by adding", "gap by adding a", "by adding a nucleotide", "adding a nucleotide complementary", "a nucleotide complementary to", "nucleotide complementary to the", "complementary to the undamaged", "to the undamaged dna", "the undamaged dna strand", "undamaged dna strand to", "dna strand to the", "strand to the 3'", "to the 3' end", "the 3' end of", "3' end of the", "end of the ssb.", "of the ssb. the", "the ssb. the ssb", "ssb. the ssb is", "the ssb is subsequently", "ssb is subsequently ligated", "is subsequently ligated by", "subsequently ligated by dna", "ligated by dna ligase", "by dna ligase iii", "ligase iii lig3", "which in complex", "in complex with xrcc1", "with xrcc1 is", "xrcc1 is recruited", "is recruited to the", "recruited to the ber", "to the ber site", "the ber site by", "ber site by an", "site by an xrcc1", "by an xrcc1 mediated", "an xrcc1 mediated interaction", "xrcc1 mediated interaction with", "mediated interaction with polb", "with polb kubota", "polb kubota et", "kubota et al. 1996", "et al. 1996 .", "al. 1996 . ber", "1996 . ber proceeds", ". ber proceeds via", "proceeds via the multiple", "via the multiple nucleotide", "patch replacement pathway when", "replacement pathway when the", "pathway when the ap", "when the ap residue", "the ap residue at", "ap residue at the", "the apex1 created ssb", "apex1 created ssb undergoes", "created ssb undergoes oxidation", "ssb undergoes oxidation related", "undergoes oxidation related damage", "related damage 5'ddrp", "5'ddrp and cannot", "and cannot be cleaved", "cannot be cleaved by", "be cleaved by polb", "by polb klungland", "polb klungland and", "klungland and lindahl 1997", "and lindahl 1997 .", "lindahl 1997 . long", "1997 . long patch", ". long patch ber", "long patch ber can", "patch ber can be", "ber can be completed", "can be completed by", "be completed by polb", "completed by polb mediated", "by polb mediated dna", "polb mediated dna strand", "mediated dna strand displacement", "dna strand displacement synthesis", "strand displacement synthesis in", "displacement synthesis in the", "synthesis in the presence", "in the presence of", "the presence of parp1", "presence of parp1 or", "of parp1 or parp2", "or parp2 fen1", "parp2 fen1 and", "fen1 and dna ligase", "and dna ligase i", "ligase i lig1", "lig1 prasad", "prasad et al. 2001", "et al. 2001 .", "al. 2001 . when", "2001 . when the", ". when the pcna", "when the pcna containing", "the pcna containing replication", "pcna containing replication complex", "containing replication complex is", "replication complex is available", "is available as", "available as is", "as is the case", "is the case with", "the case with cells", "case with cells in", "with cells in s", "cells in s phase", "in s phase of", "s phase of the", "phase of the cell", "of the cell cycle", "cell cycle dna", "cycle dna strand", "strand displacement synthesis is", "displacement synthesis is catalyzed", "synthesis is catalyzed by", "is catalyzed by dna", "catalyzed by dna polymerase", "by dna polymerase delta", "polymerase delta pold", "pold or dna", "or dna polymerase epsilon", "polymerase epsilon pole", "complexes in the", "the presence of pcna", "of pcna rpa", "apex1 fen1 and", "and lig1 klungland", "lig1 klungland and", "lindahl 1997 dianova", "1997 dianova et", "dianova et al. 2001", "al. 2001 . it", "2001 . it is", ". it is likely", "it is likely that", "is likely that the", "likely that the 9", "that the 9 1", "the 9 1 1", "9 1 1 repair", "1 1 repair complex", "1 repair complex composed", "repair complex composed of", "complex composed of hus1", "of hus1 rad1", "hus1 rad1 and", "rad1 and rad9 interacts", "and rad9 interacts with", "rad9 interacts with and", "interacts with and coordinates", "with and coordinates components", "and coordinates components of", "coordinates components of ber", "of ber but", "ber but the", "but the exact mechanism", "the exact mechanism and", "exact mechanism and timing", "mechanism and timing have", "and timing have not", "timing have not been", "have not been elucidated", "been elucidated wang", "elucidated wang et", "wang et al. 2004", "al. 2004 smirnova", "2004 smirnova et", "smirnova et al. 2005", "al. 2005 guan", "2005 guan et", "guan et al. 2007", "al. 2007 balakrishnan", "2007 balakrishnan et", "balakrishnan et al. 2009", "et al. 2009 .", "resolution of ap sites can", "of ap sites can occur", "ap sites can occur through", "sites can occur through the", "can occur through the single", "occur through the single nucleotide", "through the single nucleotide replacement", "the single nucleotide replacement pathway", "single nucleotide replacement pathway or", "nucleotide replacement pathway or through", "replacement pathway or through the", "pathway or through the multiple", "or through the multiple nucleotide", "through the multiple nucleotide patch", "the multiple nucleotide patch replacement", "multiple nucleotide patch replacement pathway", "patch replacement pathway also", "replacement pathway also known", "pathway also known as", "also known as the long", "known as the long patch", "as the long patch base", "the long patch base excision", "long patch base excision repair", "base excision repair ber", "excision repair ber .", "repair ber . except", "ber . except for the", ". except for the apex1", "except for the apex1 independent", "for the apex1 independent resolution", "the apex1 independent resolution of", "apex1 independent resolution of ap", "independent resolution of ap sites", "resolution of ap sites via", "of ap sites via single", "ap sites via single nucleotide", "sites via single nucleotide base", "via single nucleotide base excision", "single nucleotide base excision repair", "nucleotide base excision repair mediated", "base excision repair mediated by", "excision repair mediated by neil1", "repair mediated by neil1 or", "mediated by neil1 or neil2", "neil1 or neil2 wiederhold", "or neil2 wiederhold et", "neil2 wiederhold et al.", "et al. 2004 das", "al. 2004 das et", "2004 das et al.", "al. 2006 single", "2006 single nucleotide", "single nucleotide and multiple nucleotide", "nucleotide and multiple nucleotide patch", "and multiple nucleotide patch replacement", "multiple nucleotide patch replacement pathways", "nucleotide patch replacement pathways are", "patch replacement pathways are both", "replacement pathways are both initiated", "pathways are both initiated by", "are both initiated by apex1", "both initiated by apex1 mediated", "initiated by apex1 mediated displacement", "by apex1 mediated displacement of", "apex1 mediated displacement of dna", "mediated displacement of dna glycosylases", "displacement of dna glycosylases and", "of dna glycosylases and cleavage", "dna glycosylases and cleavage of", "glycosylases and cleavage of the", "and cleavage of the damaged", "cleavage of the damaged dna", "of the damaged dna strand", "the damaged dna strand by", "damaged dna strand by apex1", "dna strand by apex1 immediately", "strand by apex1 immediately 5'", "by apex1 immediately 5' to", "apex1 immediately 5' to the", "immediately 5' to the ap", "5' to the ap site", "the ap site wilson", "ap site wilson et", "site wilson et al.", "et al. 1995 bennett", "al. 1995 bennett et", "1995 bennett et al.", "et al. 1997 masuda", "al. 1997 masuda et", "1997 masuda et al.", "masuda et al. 1998 .", "et al. 1998 . the", "al. 1998 . the ber", "1998 . the ber proceeds", ". the ber proceeds via", "the ber proceeds via the", "ber proceeds via the single", "proceeds via the single nucleotide", "via the single nucleotide replacement", "the single nucleotide replacement when", "single nucleotide replacement when the", "nucleotide replacement when the ap", "when the ap apurinic/apyrimidinic", "ap apurinic/apyrimidinic deoxyribose", "apurinic/apyrimidinic deoxyribose residue at", "deoxyribose residue at the 5'", "residue at the 5' end", "at the 5' end of", "the 5' end of the", "5' end of the apex1", "end of the apex1 created", "of the apex1 created single", "the apex1 created single strand", "apex1 created single strand break", "single strand break ssb", "5'drp can be removed", "can be removed by the", "be removed by the 5'", "removed by the 5' exonuclease", "by the 5' exonuclease activity", "the 5' exonuclease activity of", "5' exonuclease activity of dna", "exonuclease activity of dna polymerase", "activity of dna polymerase beta", "dna polymerase beta polb", "polb bennett et", "bennett et al. 1997 .", "et al. 1997 . polb", "al. 1997 . polb fills", "1997 . polb fills the", ". polb fills the created", "polb fills the created single", "fills the created single nucleotide", "the created single nucleotide gap", "created single nucleotide gap by", "single nucleotide gap by adding", "nucleotide gap by adding a", "gap by adding a nucleotide", "by adding a nucleotide complementary", "adding a nucleotide complementary to", "a nucleotide complementary to the", "nucleotide complementary to the undamaged", "complementary to the undamaged dna", "to the undamaged dna strand", "the undamaged dna strand to", "undamaged dna strand to the", "dna strand to the 3'", "strand to the 3' end", "to the 3' end of", "the 3' end of the", "3' end of the ssb.", "end of the ssb. the", "of the ssb. the ssb", "the ssb. the ssb is", "ssb. the ssb is subsequently", "the ssb is subsequently ligated", "ssb is subsequently ligated by", "is subsequently ligated by dna", "subsequently ligated by dna ligase", "ligated by dna ligase iii", "dna ligase iii lig3", "iii lig3 which", "lig3 which in", "which in complex with", "complex with xrcc1 is", "with xrcc1 is recruited", "xrcc1 is recruited to", "is recruited to the ber", "recruited to the ber site", "to the ber site by", "the ber site by an", "ber site by an xrcc1", "site by an xrcc1 mediated", "by an xrcc1 mediated interaction", "an xrcc1 mediated interaction with", "xrcc1 mediated interaction with polb", "interaction with polb kubota", "with polb kubota et", "polb kubota et al.", "kubota et al. 1996 .", "et al. 1996 . ber", "al. 1996 . ber proceeds", "1996 . ber proceeds via", ". ber proceeds via the", "ber proceeds via the multiple", "proceeds via the multiple nucleotide", "via the multiple nucleotide patch", "nucleotide patch replacement pathway when", "patch replacement pathway when the", "replacement pathway when the ap", "pathway when the ap residue", "when the ap residue at", "the ap residue at the", "ap residue at the 5'", "of the apex1 created ssb", "the apex1 created ssb undergoes", "apex1 created ssb undergoes oxidation", "created ssb undergoes oxidation related", "ssb undergoes oxidation related damage", "oxidation related damage 5'ddrp", "damage 5'ddrp and", "5'ddrp and cannot be", "and cannot be cleaved by", "cannot be cleaved by polb", "cleaved by polb klungland", "by polb klungland and", "polb klungland and lindahl", "klungland and lindahl 1997 .", "and lindahl 1997 . long", "lindahl 1997 . long patch", "1997 . long patch ber", ". long patch ber can", "long patch ber can be", "patch ber can be completed", "ber can be completed by", "can be completed by polb", "be completed by polb mediated", "completed by polb mediated dna", "by polb mediated dna strand", "polb mediated dna strand displacement", "mediated dna strand displacement synthesis", "dna strand displacement synthesis in", "strand displacement synthesis in the", "displacement synthesis in the presence", "synthesis in the presence of", "in the presence of parp1", "the presence of parp1 or", "presence of parp1 or parp2", "parp1 or parp2 fen1", "or parp2 fen1 and", "parp2 fen1 and dna", "fen1 and dna ligase i", "dna ligase i lig1", "lig1 prasad et", "prasad et al. 2001 .", "et al. 2001 . when", "al. 2001 . when the", "2001 . when the pcna", ". when the pcna containing", "when the pcna containing replication", "the pcna containing replication complex", "pcna containing replication complex is", "containing replication complex is available", "complex is available as", "is available as is", "available as is the", "as is the case with", "is the case with cells", "the case with cells in", "case with cells in s", "with cells in s phase", "cells in s phase of", "in s phase of the", "s phase of the cell", "phase of the cell cycle", "the cell cycle dna", "cell cycle dna strand", "cycle dna strand displacement", "dna strand displacement synthesis is", "strand displacement synthesis is catalyzed", "displacement synthesis is catalyzed by", "synthesis is catalyzed by dna", "is catalyzed by dna polymerase", "catalyzed by dna polymerase delta", "dna polymerase delta pold", "delta pold or", "pold or dna polymerase", "dna polymerase epsilon pole", "epsilon pole complexes", "pole complexes in", "complexes in the presence", "in the presence of pcna", "presence of pcna rpa", "pcna rpa rfc", "rpa rfc apex1", "rfc apex1 fen1", "apex1 fen1 and lig1", "fen1 and lig1 klungland", "and lig1 klungland and", "lig1 klungland and lindahl", "and lindahl 1997 dianova", "lindahl 1997 dianova et", "1997 dianova et al.", "dianova et al. 2001 .", "et al. 2001 . it", "al. 2001 . it is", "2001 . it is likely", ". it is likely that", "it is likely that the", "is likely that the 9", "likely that the 9 1", "that the 9 1 1", "the 9 1 1 repair", "9 1 1 repair complex", "1 1 repair complex composed", "1 repair complex composed of", "repair complex composed of hus1", "composed of hus1 rad1", "of hus1 rad1 and", "hus1 rad1 and rad9", "rad1 and rad9 interacts with", "and rad9 interacts with and", "rad9 interacts with and coordinates", "interacts with and coordinates components", "with and coordinates components of", "and coordinates components of ber", "components of ber but", "of ber but the", "ber but the exact", "but the exact mechanism and", "the exact mechanism and timing", "exact mechanism and timing have", "mechanism and timing have not", "and timing have not been", "timing have not been elucidated", "not been elucidated wang", "been elucidated wang et", "elucidated wang et al.", "et al. 2004 smirnova", "al. 2004 smirnova et", "2004 smirnova et al.", "et al. 2005 guan", "al. 2005 guan et", "2005 guan et al.", "et al. 2007 balakrishnan", "al. 2007 balakrishnan et", "2007 balakrishnan et al.", "balakrishnan et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1796", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "73943", "r hsa", "hsa 73943", "r hsa 73943" ] }, { "record_id": "GLY_000594_1_1796", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "reversal of", "of alkylation", "alkylation damage", "damage by", "by dna", "dna dioxygenases", "reversal of alkylation", "of alkylation damage", "alkylation damage by", "damage by dna", "by dna dioxygenases", "reversal of alkylation damage", "of alkylation damage by", "alkylation damage by dna", "damage by dna dioxygenases", "reversal of alkylation damage by", "of alkylation damage by dna", "alkylation damage by dna dioxygenases", "dna in", "in cells", "cells is", "is susceptible", "susceptible to", "to different", "different types", "types of", "of cytotoxic", "cytotoxic and", "and mutagenic", "mutagenic damage", "damage caused", "caused by", "by alkylating", "alkylating agents.", "agents. these", "these genotoxic", "genotoxic chemicals", "chemicals generate", "generate major", "major lesions", "lesions like", "like 1", "1 methyladenine", "3 methyladenine", "3 methylcytosine", "methylcytosine and", "and o6", "o6 methylguanine", "methylguanine in", "in dna.", "dna. cells", "cells have", "have built", "built in", "in repair", "repair mechanisms", "mechanisms against", "against such", "such toxic", "toxic molecules.", "molecules. for", "for example", "3 methyladeninie", "methyladeninie dna", "dna glycosylases", "glycosylases excise", "excise some", "some methylated", "methylated bases", "bases while", "while mgmt/hagt", "mgmt/hagt protein", "protein transfers", "transfers alkyl", "alkyl groups", "groups from", "from others", "others lesions", "lesions onto", "onto cysteine", "cysteine residues.", "residues. e.coli", "e.coli alkb", "alkb protein", "protein has", "has a", "a unique", "unique function", "function wherein", "wherein 1", "methyladenine and", "and 3", "methylcytosine are", "are demethylated", "demethylated by", "by a", "a combination", "combination of", "of oxidative", "oxidative decarboxylation", "decarboxylation and", "and hydroxylation", "hydroxylation activities.", "activities. alkb", "alkb and", "and its", "its human", "human orthologs", "and alkbh3", "belong to", "to alpha", "alpha ketoglutarate", "ketoglutarate deoxygenase", "deoxygenase family", "family of", "of enzymes", "enzymes that", "that oxidize", "oxidize chemically", "chemically inert", "inert compounds", "compounds in", "in the", "the presence", "presence of", "of alpha", "oxygen and", "and ferrous", "ferrous ions.", "ions. as", "as a", "a byproduct", "byproduct of", "of these", "these chemical", "chemical reactions", "formaldehyde is", "is released", "released in", "the case", "case of", "of methylated", "methylated lesions", "lesions and", "and acetaldehyde", "acetaldehyde in", "case 1", "1 ethyladenine", "ethyladenine in", "dna. co2", "co2 and", "and succinate", "succinate are", "are also", "also released", "in an", "an intermediate", "intermediate step", "step not", "not shown", "shown in", "the following", "following illustration.", "illustration. unlike", "unlike other", "other mechanisms", "mechanisms which", "which involve", "involve some", "some kind", "kind of", "of nuclease", "nuclease activities", "this type", "type of", "of repair", "repair mechanism", "mechanism leaves", "leaves the", "the repaired", "repaired bases", "bases intact", "intact by", "by just", "just removing", "removing the", "the reactive", "reactive alkyl", "groups that", "that get", "get bound", "bound to", "to the", "the bases", "bases thereby", "thereby effecting", "effecting accurate", "accurate restoration", "restoration of", "of damaged", "damaged dna", "dna sequences", "trewick et", "et al.", "al. 2002", "duncan et", "sedgwick 2004", "2004 .", "dna in cells", "in cells is", "cells is susceptible", "is susceptible to", "susceptible to different", "to different types", "different types of", "types of cytotoxic", "of cytotoxic and", "cytotoxic and mutagenic", "and mutagenic damage", "mutagenic damage caused", "damage caused by", "caused by alkylating", "by alkylating agents.", "alkylating agents. these", "agents. these genotoxic", "these genotoxic chemicals", "genotoxic chemicals generate", "chemicals generate major", "generate major lesions", "major lesions like", "lesions like 1", "like 1 methyladenine", "methyladenine 3", "3 methylcytosine and", "methylcytosine and o6", "and o6 methylguanine", "o6 methylguanine in", "methylguanine in dna.", "in dna. cells", "dna. cells have", "cells have built", "have built in", "built in repair", "in repair mechanisms", "repair mechanisms against", "mechanisms against such", "against such toxic", "such toxic molecules.", "toxic molecules. for", "molecules. for example", "example 3", "3 methyladeninie dna", "methyladeninie dna glycosylases", "dna glycosylases excise", "glycosylases excise some", "excise some methylated", "some methylated bases", "methylated bases while", "bases while mgmt/hagt", "while mgmt/hagt protein", "mgmt/hagt protein transfers", "protein transfers alkyl", "transfers alkyl groups", "alkyl groups from", "groups from others", "from others lesions", "others lesions onto", "lesions onto cysteine", "onto cysteine residues.", "cysteine residues. e.coli", "residues. e.coli alkb", "e.coli alkb protein", "alkb protein has", "protein has a", "has a unique", "a unique function", "unique function wherein", "function wherein 1", "wherein 1 methyladenine", "1 methyladenine and", "methyladenine and 3", "and 3 methylcytosine", "3 methylcytosine are", "methylcytosine are demethylated", "are demethylated by", "demethylated by a", "by a combination", "a combination of", "combination of oxidative", "of oxidative decarboxylation", "oxidative decarboxylation and", "decarboxylation and hydroxylation", "and hydroxylation activities.", "hydroxylation activities. alkb", "activities. alkb and", "alkb and its", "and its human", "its human orthologs", "orthologs alkbh2", "alkbh2 abh2", "abh2 and", "alkbh3 abh3", "abh3 belong", "belong to alpha", "to alpha ketoglutarate", "alpha ketoglutarate deoxygenase", "ketoglutarate deoxygenase family", "deoxygenase family of", "family of enzymes", "of enzymes that", "enzymes that oxidize", "that oxidize chemically", "oxidize chemically inert", "chemically inert compounds", "inert compounds in", "compounds in the", "in the presence", "the presence of", "presence of alpha", "of alpha ketoglutarate", "ketoglutarate oxygen", "oxygen and ferrous", "and ferrous ions.", "ferrous ions. as", "ions. as a", "as a byproduct", "a byproduct of", "byproduct of these", "of these chemical", "these chemical reactions", "reactions formaldehyde", "formaldehyde is released", "is released in", "released in the", "in the case", "the case of", "case of methylated", "of methylated lesions", "methylated lesions and", "lesions and acetaldehyde", "and acetaldehyde in", "acetaldehyde in the", "the case 1", "case 1 ethyladenine", "1 ethyladenine in", "ethyladenine in dna.", "in dna. co2", "dna. co2 and", "co2 and succinate", "and succinate are", "succinate are also", "are also released", "also released in", "released in an", "in an intermediate", "an intermediate step", "intermediate step not", "step not shown", "not shown in", "shown in the", "in the following", "the following illustration.", "following illustration. unlike", "illustration. unlike other", "unlike other mechanisms", "other mechanisms which", "mechanisms which involve", "which involve some", "involve some kind", "some kind of", "kind of nuclease", "of nuclease activities", "activities this", "this type of", "type of repair", "of repair mechanism", "repair mechanism leaves", "mechanism leaves the", "leaves the repaired", "the repaired bases", "repaired bases intact", "bases intact by", "intact by just", "by just removing", "just removing the", "removing the reactive", "the reactive alkyl", "reactive alkyl groups", "alkyl groups that", "groups that get", "that get bound", "get bound to", "bound to the", "to the bases", "the bases thereby", "bases thereby effecting", "thereby effecting accurate", "effecting accurate restoration", "accurate restoration of", "restoration of damaged", "of damaged dna", "damaged dna sequences", "sequences trewick", "trewick et al.", "et al. 2002", "2002 duncan", "duncan et al.", "2002 sedgwick", "sedgwick 2004 .", "dna in cells is", "in cells is susceptible", "cells is susceptible to", "is susceptible to different", "susceptible to different types", "to different types of", "different types of cytotoxic", "types of cytotoxic and", "of cytotoxic and mutagenic", "cytotoxic and mutagenic damage", "and mutagenic damage caused", "mutagenic damage caused by", "damage caused by alkylating", "caused by alkylating agents.", "by alkylating agents. these", "alkylating agents. these genotoxic", "agents. these genotoxic chemicals", "these genotoxic chemicals generate", "genotoxic chemicals generate major", "chemicals generate major lesions", "generate major lesions like", "major lesions like 1", "lesions like 1 methyladenine", "1 methyladenine 3", "methyladenine 3 methyladenine", "3 methyladenine 3", "methyladenine 3 methylcytosine", "3 methylcytosine and o6", "methylcytosine and o6 methylguanine", "and o6 methylguanine in", "o6 methylguanine in dna.", "methylguanine in dna. cells", "in dna. cells have", "dna. cells have built", "cells have built in", "have built in repair", "built in repair mechanisms", "in repair mechanisms against", "repair mechanisms against such", "mechanisms against such toxic", "against such toxic molecules.", "such toxic molecules. for", "toxic molecules. for example", "for example 3", "example 3 methyladeninie", "3 methyladeninie dna glycosylases", "methyladeninie dna glycosylases excise", "dna glycosylases excise some", "glycosylases excise some methylated", "excise some methylated bases", "some methylated bases while", "methylated bases while mgmt/hagt", "bases while mgmt/hagt protein", "while mgmt/hagt protein transfers", "mgmt/hagt protein transfers alkyl", "protein transfers alkyl groups", "transfers alkyl groups from", "alkyl groups from others", "groups from others lesions", "from others lesions onto", "others lesions onto cysteine", "lesions onto cysteine residues.", "onto cysteine residues. e.coli", "cysteine residues. e.coli alkb", "residues. e.coli alkb protein", "e.coli alkb protein has", "alkb protein has a", "protein has a unique", "has a unique function", "a unique function wherein", "unique function wherein 1", "function wherein 1 methyladenine", "wherein 1 methyladenine and", "1 methyladenine and 3", "methyladenine and 3 methylcytosine", "and 3 methylcytosine are", "3 methylcytosine are demethylated", "methylcytosine are demethylated by", "are demethylated by a", "demethylated by a combination", "by a combination of", "a combination of oxidative", "combination of oxidative decarboxylation", "of oxidative decarboxylation and", "oxidative decarboxylation and hydroxylation", "decarboxylation and hydroxylation activities.", "and hydroxylation activities. alkb", "hydroxylation activities. alkb and", "activities. alkb and its", "alkb and its human", "and its human orthologs", "human orthologs alkbh2", "abh2 and alkbh3", "and alkbh3 abh3", "abh3 belong to", "belong to alpha ketoglutarate", "to alpha ketoglutarate deoxygenase", "alpha ketoglutarate deoxygenase family", "ketoglutarate deoxygenase family of", "deoxygenase family of enzymes", "family of enzymes that", "of enzymes that oxidize", "enzymes that oxidize chemically", "that oxidize chemically inert", "oxidize chemically inert compounds", "chemically inert compounds in", "inert compounds in the", "compounds in the presence", "in the presence of", "the presence of alpha", "presence of alpha ketoglutarate", "alpha ketoglutarate oxygen", "ketoglutarate oxygen and", "oxygen and ferrous ions.", "and ferrous ions. as", "ferrous ions. as a", "ions. as a byproduct", "as a byproduct of", "a byproduct of these", "byproduct of these chemical", "of these chemical reactions", "chemical reactions formaldehyde", "reactions formaldehyde is", "formaldehyde is released in", "is released in the", "released in the case", "in the case of", "the case of methylated", "case of methylated lesions", "of methylated lesions and", "methylated lesions and acetaldehyde", "lesions and acetaldehyde in", "and acetaldehyde in the", "acetaldehyde in the case", "in the case 1", "the case 1 ethyladenine", "case 1 ethyladenine in", "1 ethyladenine in dna.", "ethyladenine in dna. co2", "in dna. co2 and", "dna. co2 and succinate", "co2 and succinate are", "and succinate are also", "succinate are also released", "are also released in", "also released in an", "released in an intermediate", "in an intermediate step", "an intermediate step not", "intermediate step not shown", "step not shown in", "not shown in the", "shown in the following", "in the following illustration.", "the following illustration. unlike", "following illustration. unlike other", "illustration. unlike other mechanisms", "unlike other mechanisms which", "other mechanisms which involve", "mechanisms which involve some", "which involve some kind", "involve some kind of", "some kind of nuclease", "kind of nuclease activities", "nuclease activities this", "activities this type", "this type of repair", "type of repair mechanism", "of repair mechanism leaves", "repair mechanism leaves the", "mechanism leaves the repaired", "leaves the repaired bases", "the repaired bases intact", "repaired bases intact by", "bases intact by just", "intact by just removing", "by just removing the", "just removing the reactive", "removing the reactive alkyl", "the reactive alkyl groups", "reactive alkyl groups that", "alkyl groups that get", "groups that get bound", "that get bound to", "get bound to the", "bound to the bases", "to the bases thereby", "the bases thereby effecting", "bases thereby effecting accurate", "thereby effecting accurate restoration", "effecting accurate restoration of", "accurate restoration of damaged", "restoration of damaged dna", "of damaged dna sequences", "dna sequences trewick", "sequences trewick et", "trewick et al. 2002", "al. 2002 duncan", "2002 duncan et", "duncan et al. 2002", "al. 2002 sedgwick", "2002 sedgwick 2004", "dna in cells is susceptible", "in cells is susceptible to", "cells is susceptible to different", "is susceptible to different types", "susceptible to different types of", "to different types of cytotoxic", "different types of cytotoxic and", "types of cytotoxic and mutagenic", "of cytotoxic and mutagenic damage", "cytotoxic and mutagenic damage caused", "and mutagenic damage caused by", "mutagenic damage caused by alkylating", "damage caused by alkylating agents.", "caused by alkylating agents. these", "by alkylating agents. these genotoxic", "alkylating agents. these genotoxic chemicals", "agents. these genotoxic chemicals generate", "these genotoxic chemicals generate major", "genotoxic chemicals generate major lesions", "chemicals generate major lesions like", "generate major lesions like 1", "major lesions like 1 methyladenine", "like 1 methyladenine 3", "1 methyladenine 3 methyladenine", "3 methyladenine 3 methylcytosine", "methyladenine 3 methylcytosine and", "3 methylcytosine and o6 methylguanine", "methylcytosine and o6 methylguanine in", "and o6 methylguanine in dna.", "o6 methylguanine in dna. cells", "methylguanine in dna. cells have", "in dna. cells have built", "dna. cells have built in", "cells have built in repair", "have built in repair mechanisms", "built in repair mechanisms against", "in repair mechanisms against such", "repair mechanisms against such toxic", "mechanisms against such toxic molecules.", "against such toxic molecules. for", "such toxic molecules. for example", "molecules. for example 3", "for example 3 methyladeninie", "example 3 methyladeninie dna", "3 methyladeninie dna glycosylases excise", "methyladeninie dna glycosylases excise some", "dna glycosylases excise some methylated", "glycosylases excise some methylated bases", "excise some methylated bases while", "some methylated bases while mgmt/hagt", "methylated bases while mgmt/hagt protein", "bases while mgmt/hagt protein transfers", "while mgmt/hagt protein transfers alkyl", "mgmt/hagt protein transfers alkyl groups", "protein transfers alkyl groups from", "transfers alkyl groups from others", "alkyl groups from others lesions", "groups from others lesions onto", "from others lesions onto cysteine", "others lesions onto cysteine residues.", "lesions onto cysteine residues. e.coli", "onto cysteine residues. e.coli alkb", "cysteine residues. e.coli alkb protein", "residues. e.coli alkb protein has", "e.coli alkb protein has a", "alkb protein has a unique", "protein has a unique function", "has a unique function wherein", "a unique function wherein 1", "unique function wherein 1 methyladenine", "function wherein 1 methyladenine and", "wherein 1 methyladenine and 3", "1 methyladenine and 3 methylcytosine", "methyladenine and 3 methylcytosine are", "and 3 methylcytosine are demethylated", "3 methylcytosine are demethylated by", "methylcytosine are demethylated by a", "are demethylated by a combination", "demethylated by a combination of", "by a combination of oxidative", "a combination of oxidative decarboxylation", "combination of oxidative decarboxylation and", "of oxidative decarboxylation and hydroxylation", "oxidative decarboxylation and hydroxylation activities.", "decarboxylation and hydroxylation activities. alkb", "and hydroxylation activities. alkb and", "hydroxylation activities. alkb and its", "activities. alkb and its human", "alkb and its human orthologs", "its human orthologs alkbh2", "orthologs alkbh2 abh2", "alkbh2 abh2 and", "alkbh3 abh3 belong", "abh3 belong to alpha", "belong to alpha ketoglutarate deoxygenase", "to alpha ketoglutarate deoxygenase family", "alpha ketoglutarate deoxygenase family of", "ketoglutarate deoxygenase family of enzymes", "deoxygenase family of enzymes that", "family of enzymes that oxidize", "of enzymes that oxidize chemically", "enzymes that oxidize chemically inert", "that oxidize chemically inert compounds", "oxidize chemically inert compounds in", "chemically inert compounds in the", "inert compounds in the presence", "compounds in the presence of", "in the presence of alpha", "the presence of alpha ketoglutarate", "of alpha ketoglutarate oxygen", "alpha ketoglutarate oxygen and", "ketoglutarate oxygen and ferrous", "oxygen and ferrous ions. as", "and ferrous ions. as a", "ferrous ions. as a byproduct", "ions. as a byproduct of", "as a byproduct of these", "a byproduct of these chemical", "byproduct of these chemical reactions", "these chemical reactions formaldehyde", "chemical reactions formaldehyde is", "reactions formaldehyde is released", "formaldehyde is released in the", "is released in the case", "released in the case of", "in the case of methylated", "the case of methylated lesions", "case of methylated lesions and", "of methylated lesions and acetaldehyde", "methylated lesions and acetaldehyde in", "lesions and acetaldehyde in the", "and acetaldehyde in the case", "acetaldehyde in the case 1", "in the case 1 ethyladenine", "the case 1 ethyladenine in", "case 1 ethyladenine in dna.", "1 ethyladenine in dna. co2", "ethyladenine in dna. co2 and", "in dna. co2 and succinate", "dna. co2 and succinate are", "co2 and succinate are also", "and succinate are also released", "succinate are also released in", "are also released in an", "also released in an intermediate", "released in an intermediate step", "in an intermediate step not", "an intermediate step not shown", "intermediate step not shown in", "step not shown in the", "not shown in the following", "shown in the following illustration.", "in the following illustration. unlike", "the following illustration. unlike other", "following illustration. unlike other mechanisms", "illustration. unlike other mechanisms which", "unlike other mechanisms which involve", "other mechanisms which involve some", "mechanisms which involve some kind", "which involve some kind of", "involve some kind of nuclease", "some kind of nuclease activities", "of nuclease activities this", "nuclease activities this type", "activities this type of", "this type of repair mechanism", "type of repair mechanism leaves", "of repair mechanism leaves the", "repair mechanism leaves the repaired", "mechanism leaves the repaired bases", "leaves the repaired bases intact", "the repaired bases intact by", "repaired bases intact by just", "bases intact by just removing", "intact by just removing the", "by just removing the reactive", "just removing the reactive alkyl", "removing the reactive alkyl groups", "the reactive alkyl groups that", "reactive alkyl groups that get", "alkyl groups that get bound", "groups that get bound to", "that get bound to the", "get bound to the bases", "bound to the bases thereby", "to the bases thereby effecting", "the bases thereby effecting accurate", "bases thereby effecting accurate restoration", "thereby effecting accurate restoration of", "effecting accurate restoration of damaged", "accurate restoration of damaged dna", "restoration of damaged dna sequences", "damaged dna sequences trewick", "dna sequences trewick et", "sequences trewick et al.", "et al. 2002 duncan", "al. 2002 duncan et", "2002 duncan et al.", "et al. 2002 sedgwick", "al. 2002 sedgwick 2004", "2002 sedgwick 2004 ." ] }, { "record_id": "GLY_000594_1_1797", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75094", "r hsa", "hsa 75094", "r hsa 75094" ] }, { "record_id": "GLY_000594_1_1797", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of the", "the editosome", "formation of the", "of the 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"editosome for c to u", "for c to u editing", "c to u editing in", "to u editing in mammals", "u editing in mammals consist", "editing in mammals consist of", "in mammals consist of a", "mammals consist of a member", "consist of a member of", "of a member of cytidine", "a member of cytidine deaminase", "member of cytidine deaminase family", "of cytidine deaminase family of", "cytidine deaminase family of enzymes", "family of enzymes apob", "of enzymes apob mrna", "enzymes apob mrna editig", "apob mrna editig catalytic polypeptide", "mrna editig catalytic polypeptide 1", "catalytic polypeptide 1 apobec", "polypeptide 1 apobec 1", "apobec 1 and a", "1 and a complementing", "and a complementing specificity factor", "complementing specificity factor acf", "factor acf in", "acf in addition to", "in addition to the target", "addition to the target mrna." ] }, { "record_id": "GLY_000594_1_1798", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "75102", "r hsa", "hsa 75102", "r hsa 75102" ] }, { "record_id": "GLY_000594_1_1798", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "c6 deamination", "deamination of", "of adenosine", "c6 deamination of", "deamination of adenosine", "c6 deamination of adenosine", "hydrolytic deamination", "adenosine leads", "leads to", "to inosine.", "inosine. ammonia", "ammonia is", "is presumed", "presumed to", "to be", "be released", "released during", "during this", "this reaction.
              ", "hydrolytic deamination of", "of adenosine leads", "adenosine leads to", "leads to inosine.", "to inosine. ammonia", "inosine. ammonia is", "ammonia is presumed", "is presumed to", "presumed to be", "to be released", "be released during", "released during this", "during this reaction.
              ", "hydrolytic deamination of adenosine", "deamination of adenosine leads", "of adenosine leads to", "adenosine leads to inosine.", "leads to inosine. ammonia", "to inosine. ammonia is", "inosine. ammonia is presumed", "ammonia is presumed to", "is presumed to be", "presumed to be released", "to be released during", "be released during this", "released during this reaction.
              ", "hydrolytic deamination of adenosine leads", "deamination of adenosine leads to", "of adenosine leads to inosine.", "adenosine leads to inosine. ammonia", "leads to inosine. ammonia is", "to inosine. ammonia is presumed", "inosine. ammonia is presumed to", "ammonia is presumed to be", "is presumed to be released", "presumed to be released during", "to be released during this", "be released during this reaction.
              " ] }, { "record_id": "GLY_000594_1_1799", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77042", "r hsa", "hsa 77042", "r hsa 77042" ] }, { "record_id": "GLY_000594_1_1799", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of editosomes", "editosomes by", "by adar", "adar proteins", "formation of editosomes", "of editosomes by", "editosomes by adar", "by adar proteins", "formation of editosomes by", "of editosomes by adar", "editosomes by adar proteins", "formation of editosomes by adar", "of editosomes by adar proteins", "it is", "is still", "still unclear", "unclear how", "adar 1", "1 and", "and adar", "adar 2", "2 proteins", "proteins form", "form the", "the editosomes", "editosomes with", "with the", "the target", "target rna.", "rna. other", "other components", "components of", "of these", "these editosomes", "editosomes for", "for a", "a to", "to i", "i editing", "editing are", "are unknown.", "unknown.
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              ", "it is still unclear", "is still unclear how", "unclear how adar", "how adar 1", "adar 1 and adar", "1 and adar 2", "and adar 2 proteins", "adar 2 proteins form", "2 proteins form the", "proteins form the editosomes", "form the editosomes with", "the editosomes with the", "editosomes with the target", "with the target rna.", "the target rna. other", "target rna. other components", "rna. other components of", "other components of these", "components of these editosomes", "of these editosomes for", "these editosomes for a", "editosomes for a to", "for a to i", "a to i editing", "to i editing are", "i editing are unknown.", "editing are unknown.
              ", "it is still unclear how", "still unclear how adar", "unclear how adar 1", "how adar 1 and", "adar 1 and adar 2", "1 and adar 2 proteins", "and adar 2 proteins form", "adar 2 proteins form the", "2 proteins form the editosomes", "proteins form the editosomes with", "form the editosomes with the", "the editosomes with the target", "editosomes with the target rna.", "with the target rna. other", "the target rna. other components", "target rna. other components of", "rna. other components of these", "other components of these editosomes", "components of these editosomes for", "of these editosomes for a", "these editosomes for a to", "editosomes for a to i", "for a to i editing", "a to i editing are", "to i editing are unknown.", "i editing are unknown.
              " ] }, { "record_id": "GLY_000594_1_1800", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77285", "r hsa", "hsa 77285", "r hsa 77285" ] }, { "record_id": "GLY_000594_1_1800", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of myristoyl", "myristoyl coa", "coa to", "to lauroyl", "lauroyl coa", "beta oxidation of", "oxidation of myristoyl", "of myristoyl coa", "myristoyl coa to", "coa to lauroyl", "to lauroyl coa", "beta oxidation of myristoyl", "oxidation of myristoyl coa", "of myristoyl coa to", "myristoyl coa to lauroyl", "coa to lauroyl coa", "beta oxidation of myristoyl coa", "oxidation of myristoyl coa to", "of myristoyl coa to lauroyl", "myristoyl coa to lauroyl coa", "the second", "second pass", "pass through", "through the", "the beta", "oxidation spiral", "spiral starts", "starts with", "with the", "the saturated", "saturated fatty", 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and ketoacyl coa", "and ketoacyl coa thiolase activities", "coa thiolase activities all", "thiolase activities all present", "activities all present in", "all present in the mitochondrial", "present in the mitochondrial membrane", "in the mitochondrial membrane associated", "the mitochondrial membrane associated trifunctional", "mitochondrial membrane associated trifunctional protein." ] }, { "record_id": "GLY_000594_1_1801", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "77310", "r hsa", "hsa 77310", "r hsa 77310" ] }, { "record_id": "GLY_000594_1_1801", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "beta oxidation", "oxidation of", "of lauroyl", "lauroyl coa", "coa to", "to decanoyl", "decanoyl coa", "coa coa", "beta oxidation of", "oxidation of lauroyl", "of lauroyl coa", "lauroyl coa to", "coa to decanoyl", "to decanoyl coa", "decanoyl coa coa", "beta oxidation of lauroyl", "oxidation of 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broad substrate", "has a broad substrate specificity." ] }, { "record_id": "GLY_000594_1_1802", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "880009", "r hsa", "hsa 880009", "r hsa 880009" ] }, { "record_id": "GLY_000594_1_1802", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interconversion of", "of 2", "2 oxoglutarate", "oxoglutarate and", "and 2", "2 hydroxyglutarate", "interconversion of 2", "of 2 oxoglutarate", "2 oxoglutarate and", "oxoglutarate and 2", "and 2 hydroxyglutarate", "interconversion of 2 oxoglutarate", "of 2 oxoglutarate and", "2 oxoglutarate and 2", "oxoglutarate and 2 hydroxyglutarate", "interconversion of 2 oxoglutarate and", "of 2 oxoglutarate and 2", "2 oxoglutarate and 2 hydroxyglutarate", "the two", "two stereoisomers", "stereoisomers of", "hydroxyglutarate are", "are normally", "normally converted", "converted to", "to 2", "oxoglutarate in", "in the", "the 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"cai et al. 2013", "et al. 2013 .", "al. 2013 . in", "2013 . in addition", "in addition coding", "addition coding and", "coding and non coding", "and non coding rnas", "non coding rnas can", "coding rnas can prevent", "rnas can prevent micrornas", "can prevent micrornas from", "prevent micrornas from binding", "micrornas from binding to", "from binding to pten", "binding to pten mrna.", "to pten mrna. these", "pten mrna. these rnas", "mrna. these rnas are", "these rnas are termed", "rnas are termed competing", "are termed competing endogenous", "termed competing endogenous rnas", "competing endogenous rnas or", "endogenous rnas or cernas.", "rnas or cernas. transcripts", "or cernas. transcripts of", "cernas. transcripts of the", "transcripts of the pseudogene", "of the pseudogene ptenp1", "the pseudogene ptenp1 and", "pseudogene ptenp1 and mrnas", "ptenp1 and mrnas transcribed", "and mrnas transcribed from", "mrnas transcribed from serinc1", "from serinc1 vapa", "serinc1 vapa and", "vapa and cnot6l genes", "and cnot6l genes exhibit", "cnot6l genes exhibit this", "genes exhibit this activity", "this activity poliseno", "salmena zhang et", "al. 2011 tay", "2011 tay et", "tay et al. 2014", "et al. 2014 .", "micrornas mir 17 mir", "mir 17 mir 19a", "mir 19a mir 19b", "mir 19b mir 20a", "mir 20a mir 20b", "mir 20b mir 21", "mir 21 mir 22", "mir 22 mir 25", "mir 25 mir 26a1", "mir 26a1 mir 26a2", "mir 26a2 mir 93", "mir 93 mir 106a", "mir 106a mir 106b", "mir 106b mir 205", "mir 205 and mir", "205 and mir 214", "and mir 214 and bind", "mir 214 and bind pten", "214 and bind pten mrna", "and bind pten mrna and", "bind pten mrna and inhibit", "pten mrna and inhibit its", "mrna and inhibit its translation", "and inhibit its translation into", "inhibit its translation into protein.", "its translation into protein. these", "translation into protein. these micrornas", "into protein. these micrornas are", "protein. these micrornas are altered", "these micrornas are altered in", "micrornas are altered in cancer", "are altered in cancer and", "altered in cancer and can", "in cancer and can account", "cancer and can account for", "and can account for changes", "can account for changes in", "account for changes in pten", "for changes in pten levels.", "changes in pten levels. there", "in pten levels. there is", "pten levels. there is evidence", "levels. there is evidence that", "there is evidence that pten", "is evidence that pten mrna", "evidence that pten mrna translation", "that pten mrna translation is", "pten mrna translation is also", "mrna translation is also inhibited", "translation is also inhibited by", "is also inhibited by other", "also inhibited by other micrornas", "by other micrornas such", "other micrornas such as", "micrornas such as mir", "such as mir 302 and", "as mir 302 and mir", "mir 302 and mir 26b", "and mir 26b and", "mir 26b and these", "26b and these micrornas", "and these micrornas will be", "these micrornas will be annotated", "micrornas will be annotated when", "will be annotated when additional", "be annotated when additional experimental", "annotated when additional experimental details", "when additional experimental details become", "additional experimental details become available", "details become available meng", "become available meng et", "available meng et al.", "et al. 2007 xiao", "al. 2007 xiao et", "2007 xiao et al.", "et al. 2008 yang", "al. 2008 yang et", "2008 yang et al.", "et al. 2008 huse", "al. 2008 huse et", "2008 huse et al.", "et al. 2009 kim", "al. 2009 kim et", "2009 kim et al.", "et al. 2010 poliseno", "2010 poliseno salmena", "poliseno salmena riccardi", "salmena riccardi et al.", "et al. 2010 zhang", "al. 2010 zhang et", "2010 zhang et al.", "et al. 2010 tay", "al. 2010 tay et", "2010 tay et al.", "et al. 2011 qu", "al. 2011 qu et", "2011 qu et al.", "et al. 2012 cai", "al. 2012 cai et", "2012 cai et al.", "cai et al. 2013 .", "et al. 2013 . in", "al. 2013 . in addition", ". in addition coding", "in addition coding and", "addition coding and non", "coding and non coding rnas", "and non coding rnas can", "non coding rnas can prevent", "coding rnas can prevent micrornas", "rnas can prevent micrornas from", "can prevent micrornas from binding", "prevent micrornas from binding to", "micrornas from binding to pten", "from binding to pten mrna.", "binding to pten mrna. these", "to pten mrna. these rnas", "pten mrna. these rnas are", "mrna. these rnas are termed", "these rnas are termed competing", "rnas are termed competing endogenous", "are termed competing endogenous rnas", "termed competing endogenous rnas or", "competing endogenous rnas or cernas.", "endogenous rnas or cernas. transcripts", "rnas or cernas. transcripts of", "or cernas. transcripts of the", "cernas. transcripts of the pseudogene", "transcripts of the pseudogene ptenp1", "of the pseudogene ptenp1 and", "the pseudogene ptenp1 and mrnas", "pseudogene ptenp1 and mrnas transcribed", "ptenp1 and mrnas 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context when", "context when additional", "when additional experimental", "additional experimental details", "experimental details become", "details become available.", "coding and non coding", "and non coding rnas", "non coding rnas can", "coding rnas can prevent", "rnas can prevent micrornas", "can prevent micrornas from", "prevent micrornas from binding", "micrornas from binding to", "from binding to pten", "binding to pten mrna.", "to pten mrna. these", "pten mrna. these rnas", "mrna. these rnas are", "these rnas are termed", "rnas are termed competing", "are termed competing endogenous", "termed competing endogenous rnas", "competing endogenous rnas or", "endogenous rnas or cernas.", "rnas or cernas. transcripts", "or cernas. transcripts of", "cernas. transcripts of the", "transcripts of the pseudogene", "of the pseudogene ptenp1", "the pseudogene ptenp1 and", "pseudogene ptenp1 and mrnas", "ptenp1 and mrnas transcribed", "and mrnas transcribed from", "mrnas transcribed from serinc1", "from serinc1 vapa", "serinc1 vapa and", "vapa and cnot6l genes", "and cnot6l genes exhibit", "cnot6l genes exhibit this", "genes exhibit this activity", "this activity poliseno", "activity poliseno et", "poliseno et al. 2010", "al. 2010 tay", "2010 tay et", "tay et al. 2011", "al. 2011 tay", "2011 tay et", "tay et al. 2014", "et al. 2014 .", "al. 2014 . serinc1", "2014 . serinc1 mrna", ". serinc1 mrna will", "serinc1 mrna will be", "mrna will be annotated", "will be annotated in", "be annotated in this", "annotated in this context", "in this context when", "this context when additional", "context when additional experimental", "when additional experimental details", "additional experimental details become", "experimental details become available.", "coding and non coding rnas", "and non coding rnas can", "non coding rnas can prevent", "coding rnas can prevent micrornas", "rnas can prevent micrornas from", "can prevent micrornas from binding", "prevent micrornas from binding 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"loading of the", "of the teads:yap1", "the teads:yap1 to", "teads:yap1 to the", "to the ctgf", "the ctgf promoter", "promoter thus", "thus negatively regulating", "negatively regulating transcription", "regulating transcription of", "transcription of the", "of the ctgf", "the ctgf gene", "ctgf gene which", "gene which encodes", "which encodes the", "encodes the connective", "the connective tissue", "connective tissue growth", "tissue growth factor", "factor yagi", "yagi et al.", "et al. 1999", "1999 zhao", "zhao et al.", "et al. 2008", "2008 qiao", "qiao et al.", "et al. 2016", "al. 2016 .", "association of runx3 with", "of runx3 with the", "runx3 with the teads:yap1", "with the teads:yap1 complex", "the teads:yap1 complex inhibits", "teads:yap1 complex inhibits loading", "complex inhibits loading of", "inhibits loading of the", "loading of the teads:yap1", "of the teads:yap1 to", "the teads:yap1 to the", "teads:yap1 to the ctgf", "to the ctgf promoter", "ctgf promoter thus", 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"8956319", "r hsa", "hsa 8956319", "r hsa 8956319" ] }, { "record_id": "GLY_000594_1_1813", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nucleotide catabolism", "the purine", "purine bases", "bases guanine", "guanine and", "and hypoxanthine", "derived from", "from adenine", "adenine by", "by events", "events in", "in the", "purine salvage", "salvage pathways", "are converted", "converted to", "to xanthine", "xanthine and", "and then", "then to", "to uric", "uric acid", "which is", "is excreted", "excreted from", "from the", "the body", "watts 1974", "1974 .", ". the", "the end", "end point", "point of", "of this", "this pathway", "pathway in", "in humans", "humans and", "and hominoid", "hominoid primates", "primates is", "is unusual.", "unusual. most", "most other", "other mammals", "mammals metabolize", "metabolize uric", "acid further", "further to", "to yield", "yield more", "more soluble", "soluble end", "end products", "and much", "much speculation", "speculation has", "has centered", "centered on", "on possible", "possible roles", "roles for", "for high", "high uric", "acid levels", "levels in", "in normal", "normal human", "human physiology.

              in", "physiology.

              in parallel", "parallel sequences", "sequences of", "of three", "three reactions", "reactions each", "the pyrimidines", "pyrimidines thymine", "thymine and", "and uracil", "uracil are", "to beta", "beta aminoisobutyrate", "aminoisobutyrate and", "and beta", "beta alanine", "alanine respectively.", "respectively. both", "both of", "of these", "these molecules", "molecules are", "are excreted", "excreted in", "in human", "human urine", "urine and", "and appear", "appear to", "to be", "be normal", "normal end", "products of", "of pyrimidine", "pyrimidine catabolism", "griffith 1986", "1986 .", ". mitochondrial", "mitochondrial agxt2", "can also", "also catalyze", "catalyze the", "the transamination", "transamination of", "of both", "both molecules", "molecules with", "with pyruvate", "yielding 2", "2 oxoacids", "oxoacids that", "that can", "can be", "be metabolized", "metabolized further", "further by", "by reactions", "reactions of", "of branched", "branched chain", "chain amino", "amino acid", "acid and", "and short", "short chain", "chain fatty", "fatty acid", "acid catabolism", "tamaki et", "et al.", "al. 2000", "2000 .

              hydrolysis", ".

              hydrolysis of", "of phosphate", "phosphate bonds", "bonds in", "in nucleotides", "nucleotides catalyzed", "catalyzed by", "by members", "members of", "of the", "the nudt", "nudt and", "and ntpd", "ntpd families", "families of", "of enzymes", "enzymes have", "have been", "been grouped", "grouped here", "here as", "as well", "although the", "the physiological", "physiological roles", "roles of", "these groups", "groups of", "catabolic reactions", "reactions are", "are diverse.", "the purine bases", "purine bases guanine", "bases guanine and", "guanine and hypoxanthine", "hypoxanthine derived", "derived from adenine", "from adenine by", "adenine by events", "by events in", "events in the", "in the purine", "the purine salvage", "purine salvage pathways", "pathways are", "are converted to", "converted to xanthine", "to xanthine and", "xanthine and then", "and then to", "then to uric", "to uric acid", "acid which", "which is excreted", "is excreted from", "excreted from the", "from the body", "body watts", "watts 1974 .", "1974 . the", ". the end", "the end point", "end point of", "point of this", "of this pathway", "this pathway in", "pathway in humans", "in humans and", "humans and hominoid", "and hominoid primates", "hominoid primates is", "primates is unusual.", "is unusual. most", "unusual. most other", "most other mammals", "other mammals metabolize", "mammals metabolize uric", "metabolize uric acid", "uric acid further", "acid further to", "further to yield", "to yield more", "yield more soluble", "more soluble end", "soluble end products", "products and", "and much speculation", "much speculation has", "speculation has centered", "has centered on", "centered on possible", "on possible roles", "possible roles for", "roles for high", "for high uric", "high uric acid", "uric acid levels", "acid levels in", "levels in normal", "in normal human", "normal human physiology.

              in", "human physiology.

              in parallel", "physiology.

              in parallel sequences", "parallel sequences of", "sequences of three", "of three reactions", "three reactions each", "each the", "the pyrimidines thymine", "pyrimidines thymine and", "thymine and uracil", "and uracil are", "uracil are converted", "converted to beta", "to beta aminoisobutyrate", "beta aminoisobutyrate and", "aminoisobutyrate and beta", "and beta alanine", "beta alanine respectively.", "alanine respectively. both", "respectively. both of", "both of these", "of these molecules", "these molecules are", "molecules are excreted", "are excreted in", "excreted in human", "in human urine", "human urine and", "urine and appear", "and appear to", "appear to be", "to be normal", "be normal end", "normal end products", "end products of", "products of pyrimidine", "of pyrimidine catabolism", "catabolism griffith", "griffith 1986 .", "1986 . mitochondrial", ". mitochondrial agxt2", "agxt2 however", "however can", "can also catalyze", "also catalyze the", "catalyze the transamination", "the transamination of", "transamination of both", "of both molecules", "both molecules with", "molecules with pyruvate", "pyruvate yielding", "yielding 2 oxoacids", "2 oxoacids that", "oxoacids that can", "that can be", "can be metabolized", "be metabolized further", "metabolized further by", "further by reactions", "by reactions of", "reactions of branched", "of branched chain", "branched chain amino", "chain amino acid", "amino acid and", "acid and short", "and short chain", "short chain fatty", "chain fatty acid", "fatty acid catabolism", "catabolism tamaki", "tamaki et al.", "et al. 2000", "al. 2000 .

              hydrolysis", "2000 .

              hydrolysis of", ".

              hydrolysis of phosphate", "of phosphate bonds", "phosphate bonds in", "bonds in nucleotides", "in nucleotides catalyzed", "nucleotides catalyzed by", "catalyzed by members", "by members of", "members of the", "of the nudt", "the nudt and", "nudt and ntpd", "and ntpd families", "ntpd families of", "families of enzymes", "of enzymes have", "enzymes have been", "have been grouped", "been grouped here", "grouped here as", "here as well", "well although", "although the physiological", "the physiological roles", "physiological roles of", "roles of these", "of these groups", "these groups of", "of catabolic", "catabolic reactions are", "reactions are diverse.", "the purine bases guanine", "purine bases guanine and", "bases guanine and hypoxanthine", "and hypoxanthine derived", "hypoxanthine derived from", "derived from adenine by", "from adenine by events", "adenine by events in", "by events in the", "events in the purine", "in the purine salvage", "the purine salvage pathways", "salvage pathways are", "pathways are converted", "are converted to xanthine", "converted to xanthine and", "to xanthine and then", "xanthine and then to", "and then to uric", "then to uric acid", "uric acid which", "acid which is", "which is excreted from", "is excreted from the", "excreted from the body", "the body watts", "body watts 1974", "watts 1974 . the", "1974 . the end", ". the end point", "the end point of", "end point of this", "point of this pathway", "of this pathway in", "this pathway in humans", "pathway in humans and", "in humans and hominoid", "humans and hominoid primates", "and hominoid primates is", "hominoid primates is unusual.", "primates is unusual. most", "is unusual. most other", "unusual. most other mammals", "most other mammals metabolize", "other mammals metabolize uric", "mammals metabolize uric acid", "metabolize uric acid further", "uric acid further to", "acid further to yield", "further to yield more", "to yield more soluble", "yield more soluble end", "more soluble end products", "end products and", "products and much", "and much speculation has", "much speculation has centered", "speculation has centered on", "has centered on possible", "centered on possible roles", "on possible roles for", "possible roles for high", "roles for high uric", "for high uric acid", "high uric acid levels", "uric acid levels in", "acid levels in normal", "levels in normal human", "in normal human physiology.

              in", "normal human physiology.

              in parallel", "human physiology.

              in parallel sequences", "physiology.

              in parallel sequences of", "parallel sequences of three", "sequences of three reactions", "of three reactions each", "reactions each the", "each the pyrimidines", "the pyrimidines thymine and", "pyrimidines thymine and uracil", "thymine and uracil are", "and uracil are converted", "uracil are converted to", "are converted to beta", "converted to beta aminoisobutyrate", "to beta aminoisobutyrate and", "beta aminoisobutyrate and beta", "aminoisobutyrate and beta alanine", "and beta alanine respectively.", "beta alanine respectively. both", "alanine respectively. both of", "respectively. both of these", "both of these molecules", "of these molecules are", "these molecules are excreted", "molecules are excreted in", "are excreted in human", "excreted in human urine", "in human urine and", "human urine and appear", "urine and appear to", "and appear to be", "appear to be normal", "to be normal end", "be normal end products", "normal end products of", "end products of pyrimidine", "products of pyrimidine catabolism", "pyrimidine catabolism griffith", "catabolism griffith 1986", "griffith 1986 . mitochondrial", "1986 . mitochondrial agxt2", "mitochondrial agxt2 however", "however can also", "can also catalyze the", "also catalyze the transamination", "catalyze the transamination of", "the transamination of both", "transamination of both molecules", "of both molecules with", "both molecules with pyruvate", "with pyruvate yielding", "pyruvate yielding 2", "yielding 2 oxoacids that", "2 oxoacids that can", "oxoacids that can be", "that can be metabolized", "can be metabolized further", "be metabolized further by", "metabolized further by reactions", "further by reactions of", "by reactions of branched", "reactions of branched chain", "of branched chain amino", "branched chain amino acid", "chain amino acid and", "amino acid and short", "acid and short chain", "and short chain fatty", "short chain fatty acid", "chain fatty acid catabolism", "acid catabolism tamaki", "catabolism tamaki et", "tamaki et al. 2000", "et al. 2000 .

              hydrolysis", "al. 2000 .

              hydrolysis of", "2000 .

              hydrolysis of phosphate", ".

              hydrolysis of phosphate bonds", "of phosphate bonds in", "phosphate bonds in nucleotides", "bonds in nucleotides catalyzed", "in nucleotides catalyzed by", "nucleotides catalyzed by members", "catalyzed by members of", "by members of the", "members of the nudt", "of the nudt and", "the nudt and ntpd", "nudt and ntpd families", "and ntpd families of", "ntpd families of enzymes", "families of enzymes have", "of enzymes have been", "enzymes have been grouped", "have been grouped here", "been grouped here as", "grouped here as well", "as well although", "well although the", "although the physiological roles", "the physiological roles of", "physiological roles of these", "roles of these groups", "of these groups of", "groups of catabolic", "of catabolic reactions", "catabolic reactions are diverse.", "the purine bases guanine and", "purine bases guanine and hypoxanthine", "guanine and hypoxanthine derived", "and hypoxanthine derived from", "hypoxanthine derived from adenine", "derived from adenine by events", "from adenine by events in", "adenine by events in the", "by events in the purine", "events in the purine salvage", "in the purine salvage pathways", "purine salvage pathways are", "salvage pathways are converted", "pathways are converted to", "are converted to xanthine and", "converted to xanthine and then", "to xanthine and then to", "xanthine and then to uric", "and then to uric acid", "to uric acid which", "uric acid which is", "acid which is excreted", "which is excreted from the", "is excreted from the body", "from the body watts", "the body watts 1974", "body watts 1974 .", "watts 1974 . the end", "1974 . the end point", ". the end point of", "the end point of this", "end point of this pathway", "point of this pathway in", "of this pathway in humans", "this pathway in humans and", "pathway in humans and hominoid", "in humans and hominoid primates", "humans and hominoid primates is", "and hominoid primates is unusual.", "hominoid primates is unusual. most", "primates is unusual. most other", "is unusual. most other mammals", "unusual. most other mammals metabolize", "most other mammals metabolize uric", "other mammals metabolize uric acid", "mammals metabolize uric acid further", "metabolize uric acid further to", "uric acid further to yield", "acid further to yield more", "further to yield more soluble", "to yield more soluble end", "yield more soluble end products", "soluble end products and", "end products and much", "products and much speculation", "and much speculation has centered", "much speculation has centered on", "speculation has centered on possible", "has centered on possible roles", "centered on possible roles for", "on possible roles for high", "possible roles for high uric", "roles for high uric acid", "for high uric acid levels", "high uric acid levels in", "uric acid levels in normal", "acid levels in normal human", "levels in normal human physiology.

              in", "in normal human physiology.

              in parallel", "normal human physiology.

              in parallel sequences", "human physiology.

              in parallel sequences of", "physiology.

              in parallel sequences of three", "parallel sequences of three reactions", "sequences of three reactions each", "three reactions each the", "reactions each the pyrimidines", "each the pyrimidines thymine", "the pyrimidines thymine and uracil", "pyrimidines thymine and uracil are", "thymine and uracil are converted", "and uracil are converted to", "uracil are converted to beta", "are converted to beta aminoisobutyrate", "converted to beta aminoisobutyrate and", "to beta aminoisobutyrate and beta", "beta aminoisobutyrate and beta alanine", "aminoisobutyrate and beta alanine respectively.", "and beta alanine respectively. both", "beta alanine respectively. both of", "alanine respectively. both of these", "respectively. both of these molecules", "both of these molecules are", "of these molecules are excreted", "these molecules are excreted in", "molecules are excreted in human", "are excreted in human urine", "excreted in human urine and", "in human urine and appear", "human urine and appear to", "urine and appear to be", "and appear to be normal", "appear to be normal end", "to be normal end products", "be normal end products of", "normal end products of pyrimidine", "end products of pyrimidine catabolism", "of pyrimidine catabolism griffith", "pyrimidine catabolism griffith 1986", "catabolism griffith 1986 .", "griffith 1986 . mitochondrial agxt2", ". mitochondrial agxt2 however", "agxt2 however can", "however can also catalyze", "can also catalyze the transamination", "also catalyze the transamination of", "catalyze the transamination of both", "the transamination of both molecules", "transamination of both molecules with", "of both molecules with pyruvate", "molecules with pyruvate yielding", "with pyruvate yielding 2", "pyruvate yielding 2 oxoacids", "yielding 2 oxoacids that can", "2 oxoacids that can be", "oxoacids that can be metabolized", "that can be metabolized further", "can be metabolized further by", "be metabolized further by reactions", "metabolized further by reactions of", "further by reactions of branched", "by reactions of branched chain", "reactions of branched chain amino", "of branched chain amino acid", "branched chain amino acid and", "chain amino acid and short", "amino acid and short chain", "acid and short chain fatty", "and short chain fatty acid", "short chain fatty acid catabolism", "fatty acid catabolism tamaki", "acid catabolism tamaki et", "catabolism tamaki et al.", "tamaki et al. 2000 .

              hydrolysis", "et al. 2000 .

              hydrolysis of", "al. 2000 .

              hydrolysis of phosphate", "2000 .

              hydrolysis of phosphate bonds", ".

              hydrolysis of phosphate bonds in", "of phosphate bonds in nucleotides", "phosphate bonds in nucleotides catalyzed", "bonds in nucleotides catalyzed by", "in nucleotides catalyzed by members", "nucleotides catalyzed by members of", "catalyzed by members of the", "by members of the nudt", "members of the nudt and", "of the nudt and ntpd", "the nudt and ntpd families", "nudt and ntpd families of", "and ntpd families of enzymes", "ntpd families of enzymes have", "families of enzymes have been", "of enzymes have been grouped", "enzymes have been grouped here", "have been grouped here as", "been grouped here as well", "here as well although", "as well although the", "well although the physiological", "although the physiological roles of", "the physiological roles of these", "physiological roles of these groups", "roles of these groups of", "these groups of catabolic", "groups of catabolic reactions", "of catabolic reactions are" ] }, { "record_id": "GLY_000594_1_1814", 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al. 2012 mora", "al. 2012 mora et", "2012 mora et al.", "mora et al. 2016 .", "al. 2016 . il1f10 is", "2016 . il1f10 is synthesized", ". il1f10 is synthesized as", "il1f10 is synthesized as precursors", "is synthesized as precursors that", "synthesized as precursors that require", "as precursors that require n", "precursors that require n terminal", "that require n terminal processing", "require n terminal processing to", "n terminal processing to attain", "terminal processing to attain full", "processing to attain full receptor", "to attain full receptor agonist", "attain full receptor agonist or", "full receptor agonist or antagonist", "receptor agonist or antagonist function", "or antagonist function mora", "antagonist function mora et", "function mora et al.", "et al. 2016 . both", "al. 2016 . both full", "2016 . both full length", "both full length 1", "full length 1 \u2013", "length 1 \u2013 152", "1 \u2013 152 amino acids", "152 amino acids and", "amino acids and n", "acids and 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"fieldtype": "text", "phraselist": [ "notch4 intracellular", "intracellular domain", "domain regulates", "regulates transcription", "notch4 intracellular domain", "intracellular domain regulates", "domain regulates transcription", "notch4 intracellular domain regulates", "intracellular domain regulates transcription", "notch4 intracellular domain regulates transcription", "in the", "the nucleus", "domain fragment", "binds transcription", "transcription factors", "factors rbpj", "and mastermind", "mastermind family", "family members", "maml2 or", "or maml3", "to form", "form the", "the notch4", "notch4 co", "co activator", "activator complex", "lin et", "et al.", "al. 2002", "2002 .", ". the", "notch4 coactivator", "coactivator complex", "complex stimulates", "stimulates transcription", "transcription of", "of well", "well established", "established notch", "notch targets", "targets hes1", "hey1 and", "and hey2", "hey2 in", "in a", "a cellular", "cellular context", "context dependent", "dependent manner", "raafat et", "et al.2004", "tsunematsu et", "al. 2004", "bargo et", "al. 2010", "2010 .", ". notch4", "notch4 also", "also stimulates", "of the", "the flt4", "encoding vascular", "vascular endothelial", "endothelial growth", "growth factor", "factor receptor", "receptor 3", "shawber et", "al. 2007", "and acta2", "acta2 gene", "encoding smooth", "smooth muscle", "muscle alpha", "alpha actin", "tang et", "al. 2008", "2008 .

              nicd4", ".

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              nicd4", "2008 .

              nicd4 inhibits", ".

              nicd4 inhibits tgf", "inhibits tgf beta", "tgf beta induced", "beta induced smad", "induced smad mediated", "smad mediated transcription", "mediated transcription via", "transcription via binding", "via binding of", "binding of nicd4", "of nicd4 to", "nicd4 to tgf", "to tgf beta", "tgf beta activated", "beta activated smad3", "smad3 sun", "sun et al.", "et al. 2005", "2005 grabias", "grabias and konstantopoulos", "and konstantopoulos 2013", "konstantopoulos 2013 .", "the nucleus notch4", "nucleus notch4 intracellular", "notch4 intracellular domain fragment", "domain fragment nicd4", "nicd4 binds transcription", "binds transcription factors rbpj", "factors rbpj csl", "csl and mastermind", "and mastermind family members", "family members maml1", "maml1 maml2 or", "or maml3 to", "maml3 to form", "to form the notch4", "form the notch4 co", "the notch4 co activator", "notch4 co activator complex", "activator complex lin", "complex lin et", "lin et al. 2002", "et al. 2002 .", "al. 2002 . the", "2002 . the notch4", ". the notch4 coactivator", "the notch4 coactivator complex", "notch4 coactivator complex stimulates", "coactivator complex stimulates transcription", "complex stimulates transcription of", "stimulates transcription of well", "transcription of well established", "of well established notch", "well established notch targets", "established notch targets hes1", "targets hes1 hes5", "hes5 hey1 and", "hey1 and hey2 in", "and hey2 in a", "hey2 in a cellular", "in a cellular context", "a cellular context dependent", "cellular context dependent manner", "dependent manner lin", "manner lin et", "al. 2002 raafat", "2002 raafat et", "et al.2004 tsunematsu", "al.2004 tsunematsu et", "tsunematsu et al. 2004", "al. 2004 bargo", "2004 bargo et", "bargo et al. 2010", "et al. 2010 .", "al. 2010 . notch4", "2010 . notch4 also", ". notch4 also stimulates", "notch4 also stimulates transcription", "also stimulates transcription of", "stimulates transcription of the", "transcription of the flt4", "the flt4 vegfr3", "gene encoding vascular", "encoding vascular endothelial growth", "vascular endothelial growth factor", "endothelial growth factor receptor", "growth factor receptor 3", "receptor 3 shawber", "3 shawber et", "shawber et al. 2007", "al. 2007 and", "2007 and acta2", "acta2 gene encoding", "gene encoding smooth", "encoding smooth muscle alpha", "smooth muscle alpha actin", "alpha actin tang", "actin tang et", "tang et al. 2008", "et al. 2008 .

              nicd4", "al. 2008 .

              nicd4 inhibits", "2008 .

              nicd4 inhibits tgf", ".

              nicd4 inhibits tgf beta", "inhibits tgf beta induced", "tgf beta induced smad", "beta induced smad mediated", "induced smad mediated transcription", "smad mediated transcription via", "mediated transcription via binding", "transcription via binding of", "via binding of nicd4", "binding of nicd4 to", "of nicd4 to tgf", "nicd4 to tgf beta", "to tgf beta activated", "tgf beta activated smad3", "activated smad3 sun", "smad3 sun et", "sun et al. 2005", "al. 2005 grabias", "2005 grabias and", "grabias and konstantopoulos 2013", "and konstantopoulos 2013 .", "in the nucleus notch4", "the nucleus notch4 intracellular", "nucleus notch4 intracellular domain", "intracellular domain fragment nicd4", "fragment nicd4 binds", "nicd4 binds transcription factors", "transcription factors rbpj csl", "rbpj csl and", "csl and mastermind family", "mastermind family members maml1", "members maml1 maml2", "maml1 maml2 or maml3", "maml2 or maml3 to", "or maml3 to form", "maml3 to form the", "to form the notch4 co", "form the notch4 co activator", "the notch4 co activator complex", "co activator complex lin", "activator complex lin et", "complex lin et al.", "lin et al. 2002 .", "et al. 2002 . the", "al. 2002 . the notch4", "2002 . the notch4 coactivator", ". the notch4 coactivator complex", "the notch4 coactivator complex stimulates", "notch4 coactivator complex stimulates transcription", "coactivator complex stimulates transcription of", "complex stimulates transcription of well", "stimulates transcription of well established", "transcription of well established notch", "of well established notch targets", "well established notch targets hes1", "notch targets hes1 hes5", "hes1 hes5 hey1", "hes5 hey1 and hey2", "hey1 and hey2 in a", "and hey2 in a cellular", "hey2 in a cellular context", "in a cellular context dependent", "a cellular context dependent manner", "context dependent manner lin", "dependent manner lin et", "manner lin et al.", "et al. 2002 raafat", "al. 2002 raafat et", "2002 raafat et al.2004", "raafat et al.2004 tsunematsu", "et al.2004 tsunematsu et", "al.2004 tsunematsu et al.", "et al. 2004 bargo", "al. 2004 bargo et", "2004 bargo et al.", "bargo et al. 2010 .", "et al. 2010 . notch4", "al. 2010 . notch4 also", "2010 . notch4 also stimulates", ". notch4 also stimulates transcription", "notch4 also stimulates transcription of", "also stimulates transcription of the", "stimulates transcription of the flt4", "of the flt4 vegfr3", "flt4 vegfr3 gene", "vegfr3 gene encoding", "gene encoding vascular endothelial", "encoding vascular endothelial growth factor", "vascular endothelial growth factor receptor", "endothelial growth factor receptor 3", "factor receptor 3 shawber", "receptor 3 shawber et", "3 shawber et al.", "et al. 2007 and", "al. 2007 and acta2", "2007 and acta2 gene", "and acta2 gene encoding", "acta2 gene encoding smooth", "gene encoding smooth muscle", "encoding smooth muscle alpha actin", "muscle alpha actin tang", "alpha actin tang et", "actin tang et al.", "tang et al. 2008 .

              nicd4", "et al. 2008 .

              nicd4 inhibits", "al. 2008 .

              nicd4 inhibits tgf", "2008 .

              nicd4 inhibits tgf beta", ".

              nicd4 inhibits tgf beta induced", "inhibits tgf beta induced smad", "tgf beta induced smad mediated", "beta induced smad mediated transcription", "induced smad mediated transcription via", "smad mediated transcription via binding", "mediated transcription via binding of", "transcription via binding of nicd4", "via binding of nicd4 to", "binding of nicd4 to tgf", "of nicd4 to tgf beta", "nicd4 to tgf beta activated", "to tgf beta activated smad3", "beta activated smad3 sun", "activated smad3 sun et", "smad3 sun et al.", "et al. 2005 grabias", "al. 2005 grabias and", "2005 grabias and konstantopoulos", "grabias and konstantopoulos 2013 ." ] }, { "record_id": "GLY_000594_1_1816", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9014826", "r hsa", "hsa 9014826", "r hsa 9014826" ] }, { "record_id": "GLY_000594_1_1816", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "interleukin 36", "36 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serhan", "serhan et al. 2000", "al. 2000 2002", "2002 serhan &", "serhan & petasis 2011", "petasis 2011 maehre", "2011 maehre et", "maehre et al. 2015", "et al. 2015 .", "epa a major", "a major \u03c9 3 polyunsaturated", "major \u03c9 3 polyunsaturated fatty", "\u03c9 3 polyunsaturated fatty acid", "polyunsaturated fatty acid pufa", "acid pufa found", "pufa found in fish", "found in fish oil is", "in fish oil is the", "fish oil is the source", "oil is the source of", "is the source of e", "the source of e series", "source of e series resolvins", "e series resolvins rves", "rves one of", "one of the specialized proresolving", "of the specialized proresolving mediators", "specialized proresolving mediators spms", "mediators spms that", "spms that show potent", "that show potent anti inflammatory", "show potent anti inflammatory and", "potent anti inflammatory and pro", "anti inflammatory and pro resolving", "inflammatory and pro resolving actions", "pro resolving actions molfino", "resolving actions molfino et", "actions molfino et al.", "molfino et al. 2017 .", "et al. 2017 . the", "al. 2017 . the biosynthesis", "2017 . the biosynthesis of", ". the biosynthesis of rves", "the biosynthesis of rves occurs", "biosynthesis of rves occurs mainly", "of rves occurs mainly during", "rves occurs mainly during the", "occurs mainly during the process", "mainly during the process of", "during the process of inflammation", "the process of inflammation when", "process of inflammation when endothelial", "of inflammation when endothelial cells", "inflammation when endothelial cells interact", "when endothelial cells interact with", "endothelial cells interact with leukocytes.", "cells interact with leukocytes. epa", "with leukocytes. epa circulating", "leukocytes. epa circulating in", "epa circulating in plasma", "circulating in plasma or released/mobilised", "in plasma or released/mobilised from", "plasma or released/mobilised from damaged", "or released/mobilised from 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"kasuga et al. 2008 .", "et al. 2008 . the", "al. 2008 . the initial", "2008 . the initial transformation", ". the initial transformation of", "the initial transformation of epa", "initial transformation of epa by", "transformation of epa by aspirin", "of epa by aspirin acetylated", "epa by aspirin acetylated cyclooxygenase", "by aspirin acetylated cyclooxygenase 2", "acetylated cyclooxygenase 2 and/or", "cyclooxygenase 2 and/or cytochrome", "2 and/or cytochrome p450", "and/or cytochrome p450 mediated catalysis", "cytochrome p450 mediated catalysis can", "p450 mediated catalysis can produce", "mediated catalysis can produce stereospecific", "catalysis can produce stereospecific resolvins", "produce stereospecific resolvins 18", "stereospecific resolvins 18 r", "18 r or", "r or 18", "or 18 s rves", "18 s rves .", "s rves . combinations", "rves . combinations of oxidation", "combinations of oxidation reduction", "of oxidation reduction and", "oxidation reduction and hydrolysis", 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              mecp2", ".

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              mecp2", "2010 .

              mecp2 deletion", ".

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              mecp2", "al. 2010 .

              mecp2 deletion", "2010 .

              mecp2 deletion in", ".

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needed", "may be needed for", "be needed for pv", "needed for pv cell", "for pv cell mediated", "pv cell mediated cortical", "cell mediated cortical gaba", "mediated cortical gaba inhibition.", "cortical gaba inhibition. mecp2", "gaba inhibition. mecp2 deficient", "inhibition. mecp2 deficient cortical", "mecp2 deficient cortical pv", "deficient cortical pv cells", "cortical pv cells show", "pv cells show reduced", "cells show reduced mrna", "show reduced mrna levels", "reduced mrna levels of", "mrna levels of several", "levels of several genes", "gaba signaling such", "signaling such as", "as parvalbumin gad2", "calretinin gabra1 and", "and gabra2 as", "gabra2 as well", "as well as reduced", "well as reduced levels", "as reduced levels of", "reduced levels of glu3", "of glu3 a", "glu3 a glutamate", "a glutamate receptor subunit", "receptor subunit and", "subunit and kv3.1", "and kv3.1 a", "kv3.1 a potassium", "potassium channel he", "channel he et", "he et al. 2014", "et al. 2014 .", "mecp2 regulates expression of several", "regulates expression of several genes", "expression of several genes involved", "of several genes involved in", "several genes involved in gaba", "involved in gaba gamma", "in gaba gamma aminobutyric", "gaba gamma aminobutyric acid", "gamma aminobutyric acid signaling.", "aminobutyric acid signaling. transcription", "acid signaling. transcription of", "transcription of gad1 gad67", "gad1 gad67 and", "gad2 gad65 genes", "gad65 genes is directly", "genes is directly positively regulated", "is directly positively regulated by", "directly positively regulated by mecp2.", "positively regulated by mecp2. gad1", "regulated by mecp2. gad1 and", "by mecp2. gad1 and gad2", "mecp2. gad1 and gad2 are", "gad1 and gad2 are components", "and gad2 are components of", "gad2 are components of the", "are components of the glutamic", "components of the glutamic acid", "of the glutamic acid decarboxylase", "the glutamic acid decarboxylase complex", "glutamic acid decarboxylase complex involved", "acid decarboxylase complex involved in", "decarboxylase complex involved in production", "complex involved in production of", "involved in production of the", "in production of the neurotransmitter", "production of the neurotransmitter gaba.", "of the neurotransmitter gaba. mice", "the neurotransmitter gaba. mice lacking", "neurotransmitter gaba. mice lacking mecp2", "gaba. mice lacking mecp2 from", "mice lacking mecp2 from gaba", "lacking mecp2 from gaba releasing", "mecp2 from gaba releasing neurons", "from gaba releasing neurons have", "gaba releasing neurons have decreased", "releasing neurons have decreased gaba", "neurons have decreased gaba levels", "have decreased gaba levels and", "decreased gaba levels and exhibit", "gaba levels and exhibit multiple", "levels and exhibit multiple rett", "and exhibit multiple rett syndrome", "exhibit multiple rett syndrome features", "rett syndrome features chao", "syndrome features chao et", "features chao et al.", "chao et al. 2010 .

              mecp2", "et al. 2010 .

              mecp2 deletion", "al. 2010 .

              mecp2 deletion in", "2010 .

              mecp2 deletion in mouse", ".

              mecp2 deletion in mouse gabaergic", "deletion in mouse gabaergic parvalbumin", "in mouse gabaergic parvalbumin expressing", "gabaergic parvalbumin expressing pv", "expressing pv cells", "pv cells cortical", "cells cortical interneurons playing", "cortical interneurons playing a key", "interneurons playing a key role", "playing a key role in", "a key role in visual", "key role in visual experience", "role in visual experience induced", "in visual experience induced ocular", "visual experience induced ocular dominance", "experience induced ocular dominance plasticity", "ocular dominance plasticity does", "dominance plasticity does not", "plasticity does not result", "does not result in rett", "not result in rett like", "result in rett like phenotype", "rett like phenotype other", "like phenotype other than", "phenotype other than defects", "other than defects in motor", "than defects in motor coordination", "defects in motor coordination and", "in motor coordination and 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9616334", "r hsa 9616334" ] }, { "record_id": "GLY_000594_1_1828", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective base", "base excision", "excision repair", "repair associated", "associated with", "with neil1", "defective base excision", "base excision repair", "excision repair associated", "repair associated with", "associated with neil1", "defective base excision repair", "base excision repair associated", "excision repair associated with", "repair associated with neil1", "defective base excision repair associated", "base excision repair associated with", "excision repair associated with neil1", "neil1 is", "is an", "an enzyme", "enzyme with", "with dual", "dual dna", "dna glycosylase", "glycosylase and", "and beta/delta", "beta/delta lyase", "lyase activity", "activity involved", "involved in", "in base", "repair pathway", "the primary", "primary repair", "pathway for", "for oxidative", "oxidative dna", "dna damage.", "damage. neil1", "neil1 can", "can detect", "detect and", "and remove", "remove dna", "dna damage", "damage resulting", "resulting from", "from oxidation", "oxidation of", "of adenine", "guanine and", "and thymine", "in the", "the form", "form of", "of 4", "4 6", "6 diamino", "diamino 5", "5 formamidopyrimidine", "2 6", "diamino 4", "4 hydroxy", "hydroxy 5", "thymine glycol", "respectively. neil1", "can also", "also detect", "remove dihydrouracil", "which results", "results from", "from deamination", "deamination of", "of cytosine.", "cytosine. several", "several low", "low frequency", "frequency neil1", "neil1 polymorphisms", "present in", "in about", "about 1%", "1% of", "of general", "general population", "population in", "the united", "united states", "states have", "have been", "been reported.", "reported. different", "different polymorphisms", "polymorphisms have", "have different", "different effects", "effects on", "on neil1", "neil1 function", "and it", "it was", "was suggested", "suggested that", "that neil1", "polymorphisms and", "and neil1", "neil1 deficiency", "deficiency or", "or haploinsuficiency", "haploinsuficiency may", "may be", "be involved", "in predisposition", "predisposition to", "to cancer", "cancer and", "and in", "in metabolic", "metabolic syndrome", "roy et", "et al.", "al. 2007", "vartanian et", "al. 2006", "sampath et", "al. 2011", "prakash et", "al. 2014", "2014 .", ". one", "one polymorphism", "neil1 g83d", "is associated", "with primary", "primary sclerosing", "sclerosing cholangitis", "cholangitis and", "and cholangiocarcinoma", "forsbring et", "al. 2009", "2009 .", ". neil1", "g83d variant", "variant exhibits", "exhibits impaired", "impaired dna", "glycosylase activity", "activity towards", "towards different", "different damaged", "damaged dna", "dna bases", "and induces", "induces genomic", "genomic instability", "galick et", "al. 2017", "2017 .
              neil1", ".
              neil1 e28del", "an in", "in frame", "frame deletion", "deletion variant", "variant of", "of neil1", "neil1 reported", "reported in", "in gastric", "where glutamate", "glutamate at", "at position", "position 28", "28 is", "is deleted", "does not", "not cleave", "cleave tg", "tg from", "from damaged", "shinmura et", "al. 2004", "2004 .
              neil1", ".
              neil1 q282ter", "a neil1", "neil1 variant", "variant which", "which lacks", "lacks the", "the putative", "putative nuclear", "nuclear localization", "localization signal", "localizes to", "to the", "the cytosol", "cytosol and", "and is", "is therefore", "therefore not", "not able", "able to", "to access", "access damaged", "dna substrates", "but its", "its involvement", "involvement in", "in cancer", "cancer is", "is uncertain", "al. 2015", "2015 .
              reduced", ".
              reduced expression", "expression of", "neil1 and", "and neil2", "neil2 genes", "accompanied with", "with increased", "increased neil3", "neil3 gene", "gene expression", "expression was", "was detected", "detected in", "in various", "various cancers.", "cancers. neil1", "neil1 gene", "gene silencing", "silencing by", "by promoter", "promoter hypermethylation", "hypermethylation may", "be one", "one of", "of the", "the underlying", "underlying mechanisms", "mechanisms for", "for reduced", "reduced neil1", "neil1 expression", "expression in", "al. 2016", "2016 .
              infection", ".
              infection with", "with the", "the hepatitis", "hepatitis c", "c virus", "leads to", "to decreased", "decreased neil1", "in liver", "liver cells", "through an", "an unknown", "unknown mechanism", "pal et", "al. 2010", "2010 .
              mice", ".
              mice that", "that are", "are double", "double knockout", "knockout for", "for neil1", "and nthl1", "nthl1 genes", "genes accumulate", "accumulate dna", "damage in", "of fapya", "fapya and", "and fapyg", "fapyg and", "and are", "are more", "more prone", "prone to", "to development", "development of", "of lung", "lung adenocarcinoma", "adenocarcinoma than", "than single", "single neil1", "neil1 or", "or nthl1", "nthl1 gene", "gene knockouts", "chan et", ". another", "another study", "study reported", "reported that", "neil1 knockout", "knockout mice", "mice did", "did not", "not show", "show a", "a predisposition", "to tumour", "tumour formation", "and neither", "neither did", "did double", "double knockouts", "knockouts of", "nor triple", "triple knockouts", "neil2 and", "and neil3.", "neil3. neil1", "mice are", "are obese", "consistent with", "the metabolic", "but double", "neil2 do", "do not", "not display", "display obesity", "rolseth et", "2017 .
              ", "neil1 is an", "is an enzyme", "an enzyme with", "enzyme with dual", "with dual dna", "dual dna glycosylase", "dna glycosylase and", "glycosylase and beta/delta", "and beta/delta lyase", "beta/delta lyase activity", "lyase activity involved", "activity involved in", "involved in base", "in base excision", "excision repair pathway", "pathway ber", "the primary repair", "primary repair pathway", "repair pathway for", "pathway for oxidative", "for oxidative dna", "oxidative dna damage.", "dna damage. neil1", "damage. neil1 can", "neil1 can detect", "can detect and", "detect and remove", "and remove dna", "remove dna damage", "dna damage resulting", "damage resulting from", "resulting from oxidation", "from oxidation of", "oxidation of adenine", "adenine guanine", "guanine and thymine", "thymine in", "in the form", "the form of", "form of 4", "of 4 6", "4 6 diamino", "6 diamino 5", "diamino 5 formamidopyrimidine", "formamidopyrimidine fapya", "2 6 diamino", "6 diamino 4", "diamino 4 hydroxy", "4 hydroxy 5", "hydroxy 5 formamidopyrimidine", "formamidopyrimidine fapyg", "and thymine glycol", "glycol tg", "respectively. neil1 can", "neil1 can also", "can also detect", "also detect and", "and remove dihydrouracil", "dihydrouracil dhu", "which results from", "results from deamination", "from deamination of", "deamination of cytosine.", "of cytosine. several", "cytosine. several low", "several low frequency", "low frequency neil1", "frequency neil1 polymorphisms", "polymorphisms present", "present in about", "in about 1%", "about 1% of", "1% of general", "of general population", "general population in", "population in the", "in the united", "the united states", "united states have", "states have been", "have been reported.", "been reported. different", "reported. different polymorphisms", "different polymorphisms have", "polymorphisms have different", "have different effects", "different effects on", "effects on neil1", "on neil1 function", "function and", "and it was", "it was suggested", "was suggested that", "suggested that neil1", "that neil1 polymorphisms", "neil1 polymorphisms and", "polymorphisms and neil1", "and neil1 deficiency", "neil1 deficiency or", "deficiency or haploinsuficiency", "or haploinsuficiency may", "haploinsuficiency may be", "may be involved", "be involved in", "involved in predisposition", "in predisposition to", "predisposition to cancer", "to cancer and", "cancer and in", "and in metabolic", "in metabolic syndrome", "syndrome roy", "roy et al.", "et al. 2007", "2007 vartanian", "vartanian et al.", "et al. 2006", "2006 sampath", "sampath et al.", "et al. 2011", "2011 prakash", "prakash et al.", "et al. 2014", "al. 2014 .", "2014 . one", ". one polymorphism", "polymorphism neil1", "g83d is", "is associated with", "associated with primary", "with primary sclerosing", "primary sclerosing cholangitis", "sclerosing cholangitis and", "cholangitis and cholangiocarcinoma", "cholangiocarcinoma forsbring", "forsbring et al.", "et al. 2009", "al. 2009 .", "2009 . neil1", ". neil1 g83d", "neil1 g83d variant", "g83d variant exhibits", "variant exhibits impaired", "exhibits impaired dna", "impaired dna glycosylase", "dna glycosylase activity", "glycosylase activity towards", "activity towards different", "towards different damaged", "different damaged dna", "damaged dna bases", "bases roy", "2007 prakash", "2014 and", "and induces genomic", "induces genomic instability", "instability galick", "galick et al.", "et al. 2017", "al. 2017 .
              neil1", "2017 .
              neil1 e28del", "e28del an", "an in frame", "in frame deletion", "frame deletion variant", "deletion variant of", "variant of neil1", "of neil1 reported", "neil1 reported in", "reported in gastric", "gastric stomach", "stomach cancer", "cancer where", "where glutamate at", "glutamate at position", "at position 28", "position 28 is", "28 is deleted", "deleted does", "does not cleave", "not cleave tg", "cleave tg from", "tg from damaged", "from damaged dna", "dna shinmura", "shinmura et al.", "et al. 2004", "al. 2004 .
              neil1", "2004 .
              neil1 q282ter", "q282ter a", "a neil1 variant", "neil1 variant which", "variant which lacks", "which lacks the", "lacks the putative", "the putative nuclear", "putative nuclear localization", "nuclear localization signal", "signal nls", "localizes to the", "to the cytosol", "the cytosol and", "cytosol and is", "and is therefore", "is therefore not", "therefore not able", "not able to", "able to access", "to access damaged", "access damaged dna", "damaged dna substrates", "substrates but", "but its involvement", "its involvement in", "involvement in cancer", "in cancer is", "cancer is uncertain", "uncertain shinmura", "et al. 2015", "al. 2015 .
              reduced", "2015 .
              reduced expression", ".
              reduced expression of", "expression of neil1", "of neil1 and", "neil1 and neil2", "and neil2 genes", "genes accompanied", "accompanied with increased", "with increased neil3", "increased neil3 gene", "neil3 gene expression", "gene expression was", "expression was detected", "was detected in", "detected in various", "in various cancers.", "various cancers. neil1", "cancers. neil1 gene", "neil1 gene silencing", "gene silencing by", "silencing by promoter", "by promoter hypermethylation", "promoter hypermethylation may", "hypermethylation may be", "may be one", "be one of", "one of the", "of the underlying", "the underlying mechanisms", "underlying mechanisms for", "mechanisms for reduced", "for reduced neil1", "reduced neil1 expression", "neil1 expression in", "expression in cancer", "cancer shinmura", "et al. 2016", "al. 2016 .
              infection", "2016 .
              infection with", ".
              infection with the", "with the hepatitis", "the hepatitis c", "hepatitis c virus", "virus hcv", "hcv leads", "leads to decreased", "to decreased neil1", "decreased neil1 expression", "expression in liver", "in liver cells", "cells through", "through an unknown", "an unknown mechanism", "mechanism pal", "pal et al.", "et al. 2010", "al. 2010 .
              mice", "2010 .
              mice that", ".
              mice that are", "that are double", "are double knockout", "double knockout for", "knockout for neil1", "for neil1 and", "neil1 and nthl1", "and nthl1 genes", "nthl1 genes accumulate", "genes accumulate dna", "accumulate dna damage", "dna damage in", "damage in the", "form of fapya", "of fapya and", "fapya and fapyg", "and fapyg and", "fapyg and are", "and are more", "are more prone", "more prone to", "prone to development", "to development of", "development of lung", "of lung adenocarcinoma", "lung adenocarcinoma than", "adenocarcinoma than single", "than single neil1", "single neil1 or", "neil1 or nthl1", "or nthl1 gene", "nthl1 gene knockouts", "knockouts chan", "chan et al.", "2009 . another", ". another study", "another study reported", "study reported that", "reported that neil1", "that neil1 knockout", "neil1 knockout mice", "knockout mice did", "mice did not", "did not show", "not show a", "show a predisposition", "a predisposition to", "predisposition to tumour", "to tumour formation", "formation and", "and neither did", "neither did double", "did double knockouts", "double knockouts of", "knockouts of neil1", "neil2 nor", "nor triple knockouts", "triple knockouts of", "neil1 neil2", "neil2 and neil3.", "and neil3. neil1", "neil3. neil1 knockout", "knockout mice are", "mice are obese", "obese consistent", "consistent with the", "with the metabolic", "the metabolic syndrome", "syndrome but", "but double knockouts", "and neil2 do", "neil2 do not", "do not display", "not display obesity", "obesity rolseth", "rolseth et al.", "al. 2017 .
              ", "neil1 is an enzyme", "is an enzyme with", "an enzyme with dual", "enzyme with dual dna", "with dual dna glycosylase", "dual dna glycosylase and", "dna glycosylase and beta/delta", "glycosylase and beta/delta lyase", "and beta/delta lyase activity", "beta/delta lyase activity involved", "lyase activity involved in", "activity involved in base", "involved in base excision", "in base excision repair", "base excision repair pathway", "repair pathway ber", "ber the", "the primary repair pathway", "primary repair pathway for", "repair pathway for oxidative", "pathway for oxidative dna", "for oxidative dna damage.", "oxidative dna damage. neil1", "dna damage. neil1 can", "damage. neil1 can detect", "neil1 can detect and", "can detect and remove", "detect and remove dna", "and remove dna damage", "remove dna damage resulting", "dna damage resulting from", "damage resulting from oxidation", "resulting from oxidation of", "from oxidation of adenine", "of adenine guanine", "adenine guanine and", "and thymine in", "thymine in the", "in the form of", "the form of 4", "form of 4 6", "of 4 6 diamino", "4 6 diamino 5", "6 diamino 5 formamidopyrimidine", "5 formamidopyrimidine fapya", "fapya 2", "2 6 diamino 4", "6 diamino 4 hydroxy", "diamino 4 hydroxy 5", "4 hydroxy 5 formamidopyrimidine", "5 formamidopyrimidine fapyg", "thymine glycol tg", "tg respectively.", "respectively. neil1 can also", "neil1 can also detect", "can also detect and", "also detect and remove", "detect and remove dihydrouracil", "remove dihydrouracil dhu", "dhu which", "which results from deamination", "results from deamination of", "from deamination of cytosine.", "deamination of cytosine. several", "of cytosine. several low", "cytosine. several low frequency", "several low frequency neil1", "low frequency neil1 polymorphisms", "neil1 polymorphisms present", "polymorphisms present in", "present in about 1%", "in about 1% of", "about 1% of general", "1% of general population", "of general population in", "general population in the", "population in the united", "in the united states", "the united states have", "united states have been", "states have been reported.", "have been reported. different", "been reported. different polymorphisms", "reported. different polymorphisms have", "different polymorphisms have different", "polymorphisms have different effects", "have different effects on", "different effects on neil1", "effects on neil1 function", "neil1 function and", "function and it", "and it was suggested", "it was suggested that", "was suggested that neil1", "suggested that neil1 polymorphisms", "that neil1 polymorphisms and", "neil1 polymorphisms and neil1", "polymorphisms and neil1 deficiency", "and neil1 deficiency or", "neil1 deficiency or haploinsuficiency", "deficiency or haploinsuficiency may", "or haploinsuficiency may be", "haploinsuficiency may be involved", "may be involved in", "be involved in predisposition", "involved in predisposition to", "in predisposition to cancer", "predisposition to cancer and", "to cancer and in", "cancer and in metabolic", "and in metabolic syndrome", "metabolic syndrome roy", "syndrome roy et", "roy et al. 2007", "al. 2007 vartanian", "2007 vartanian et", "vartanian et al. 2006", "al. 2006 sampath", "2006 sampath et", "sampath et al. 2011", "al. 2011 prakash", "2011 prakash et", "prakash et al. 2014", "et al. 2014 .", "al. 2014 . one", "2014 . one polymorphism", "one polymorphism neil1", "polymorphism neil1 g83d", "neil1 g83d is", "g83d is associated", "is associated with primary", "associated with primary sclerosing", "with primary sclerosing cholangitis", "primary sclerosing cholangitis and", "sclerosing cholangitis and cholangiocarcinoma", "and cholangiocarcinoma forsbring", "cholangiocarcinoma forsbring et", "forsbring et al. 2009", "et al. 2009 .", "al. 2009 . neil1", "2009 . neil1 g83d", ". neil1 g83d variant", "neil1 g83d variant exhibits", "g83d variant exhibits impaired", "variant exhibits impaired dna", "exhibits impaired dna glycosylase", "impaired dna glycosylase activity", "dna glycosylase activity towards", "glycosylase activity towards different", "activity towards different damaged", "towards different damaged dna", "different damaged dna bases", "dna bases roy", "bases roy et", "al. 2007 prakash", "2007 prakash et", "al. 2014 and", "2014 and induces", "and induces genomic instability", "genomic instability galick", "instability galick et", "galick et al. 2017", "et al. 2017 .
              neil1", "al. 2017 .
              neil1 e28del", ".
              neil1 e28del an", "e28del an in", "an in frame deletion", "in frame deletion variant", "frame deletion variant of", "deletion variant of neil1", "variant of neil1 reported", "of neil1 reported in", "neil1 reported in gastric", "in gastric stomach", "cancer where glutamate", "where glutamate at position", "glutamate at position 28", "at position 28 is", "position 28 is deleted", "is deleted does", "deleted does not", "does not cleave tg", "not cleave tg from", "cleave tg from damaged", "tg from damaged dna", "damaged dna shinmura", "dna shinmura et", "shinmura et al. 2004", "et al. 2004 .
              neil1", "al. 2004 .
              neil1 q282ter", ".
              neil1 q282ter a", "q282ter a neil1", "a neil1 variant which", "neil1 variant which lacks", "variant which lacks the", "which lacks the putative", "lacks the putative nuclear", "the putative nuclear localization", "putative nuclear localization signal", "localization signal nls", "nls localizes", "localizes to the cytosol", "to the cytosol and", "the cytosol and is", "cytosol and is therefore", "and is therefore not", "is therefore not able", "therefore not able to", "not able to access", "able to access damaged", "to access damaged dna", "access damaged dna substrates", "dna substrates but", "substrates but its", "but its involvement in", "its involvement in cancer", "involvement in cancer is", "in cancer is uncertain", "is uncertain shinmura", "uncertain shinmura et", "shinmura et al. 2015", "et al. 2015 .
              reduced", "al. 2015 .
              reduced expression", "2015 .
              reduced expression of", ".
              reduced expression of neil1", "expression of neil1 and", "of neil1 and neil2", "neil1 and neil2 genes", "neil2 genes accompanied", "genes accompanied with", "accompanied with increased neil3", "with increased neil3 gene", "increased neil3 gene expression", "neil3 gene expression was", "gene expression was detected", "expression was detected in", "was detected in various", "detected in various cancers.", "in various cancers. neil1", "various cancers. neil1 gene", "cancers. neil1 gene silencing", "neil1 gene silencing by", "gene silencing by promoter", "silencing by promoter hypermethylation", "by promoter hypermethylation may", "promoter hypermethylation may be", "hypermethylation may be one", "may be one of", "be one of the", "one of the underlying", "of the underlying mechanisms", "the underlying mechanisms for", "underlying mechanisms for reduced", "mechanisms for reduced neil1", "for reduced neil1 expression", "reduced neil1 expression in", "neil1 expression in cancer", "in cancer shinmura", "cancer shinmura et", "shinmura et al. 2016", "et al. 2016 .
              infection", "al. 2016 .
              infection with", "2016 .
              infection with the", ".
              infection with the hepatitis", "with the hepatitis c", "the hepatitis c virus", "c virus hcv", "hcv leads to", "leads to decreased neil1", "to decreased neil1 expression", "decreased neil1 expression in", "neil1 expression in liver", "expression in liver cells", "liver cells through", "cells through an", "through an unknown mechanism", "unknown mechanism pal", "mechanism pal et", "pal et al. 2010", "et al. 2010 .
              mice", "al. 2010 .
              mice that", "2010 .
              mice that are", ".
              mice that are double", "that are double knockout", "are double knockout for", "double knockout for neil1", "knockout for neil1 and", "for neil1 and nthl1", "neil1 and nthl1 genes", "and nthl1 genes accumulate", "nthl1 genes accumulate dna", "genes accumulate dna damage", "accumulate dna damage in", "dna damage in the", "damage in the form", "the form of fapya", "form of fapya and", "of fapya and fapyg", "fapya and fapyg and", "and fapyg and are", "fapyg and are more", "and are more prone", "are more prone to", "more prone to development", "prone to development of", "to development of lung", "development of lung adenocarcinoma", "of lung adenocarcinoma than", "lung adenocarcinoma than single", "adenocarcinoma than single neil1", "than single neil1 or", "single neil1 or nthl1", "neil1 or nthl1 gene", "or nthl1 gene knockouts", "gene knockouts chan", "knockouts chan et", "chan et al. 2009", "al. 2009 . another", "2009 . another study", ". another study reported", "another study reported that", "study reported that neil1", "reported that neil1 knockout", "that neil1 knockout mice", "neil1 knockout mice did", "knockout mice did not", "mice did not show", "did not show a", "not show a predisposition", "show a predisposition to", "a predisposition to tumour", "predisposition to tumour formation", "tumour formation and", "formation and neither", "and neither did double", "neither did double knockouts", "did double knockouts of", "double knockouts of neil1", "knockouts of neil1 and", "and neil2 nor", "neil2 nor triple", "nor triple knockouts of", "triple knockouts of neil1", "of neil1 neil2", "neil1 neil2 and", "neil2 and neil3. neil1", "and neil3. neil1 knockout", "neil3. neil1 knockout mice", "neil1 knockout mice are", "knockout mice are obese", "are obese consistent", "obese consistent with", "consistent with the metabolic", "with the metabolic syndrome", "metabolic syndrome but", "syndrome but double", "but double knockouts of", "neil1 and neil2 do", "and neil2 do not", "neil2 do not display", "do not display obesity", "display obesity rolseth", "obesity rolseth et", "rolseth et al. 2017", "et al. 2017 .
              ", "neil1 is an enzyme with", "is an enzyme with dual", "an enzyme with dual dna", "enzyme with dual dna glycosylase", "with dual dna glycosylase and", "dual dna glycosylase and beta/delta", "dna glycosylase and beta/delta lyase", "glycosylase and beta/delta lyase activity", "and beta/delta lyase activity involved", "beta/delta lyase activity involved in", "lyase activity involved in base", "activity involved in base excision", "involved in base excision repair", "in base excision repair pathway", "excision repair pathway ber", "ber the primary", "the primary repair pathway for", "primary repair pathway for oxidative", "repair pathway for oxidative dna", "pathway for oxidative dna damage.", "for oxidative dna damage. neil1", "oxidative dna damage. neil1 can", "dna damage. neil1 can detect", "damage. neil1 can detect and", "neil1 can detect and remove", "can detect and remove dna", "detect and remove dna damage", "and remove dna damage resulting", "remove dna damage resulting from", "dna damage resulting from oxidation", "damage resulting from oxidation of", "resulting from oxidation of adenine", "oxidation of adenine guanine", "of adenine guanine and", "adenine guanine and thymine", "guanine and thymine in", "and thymine in the", "thymine in the form", "in the form of 4", "the form of 4 6", "form of 4 6 diamino", "of 4 6 diamino 5", "4 6 diamino 5 formamidopyrimidine", "diamino 5 formamidopyrimidine fapya", "fapya 2 6", "2 6 diamino 4 hydroxy", "6 diamino 4 hydroxy 5", "diamino 4 hydroxy 5 formamidopyrimidine", "hydroxy 5 formamidopyrimidine fapyg", "fapyg and thymine", "and thymine glycol tg", "tg respectively. neil1", "respectively. neil1 can also detect", "neil1 can also detect and", "can also detect and remove", "also detect and remove dihydrouracil", "and remove dihydrouracil dhu", "dhu which results", "which results from deamination of", "results from deamination of cytosine.", "from deamination of cytosine. several", "deamination of cytosine. several low", "of cytosine. several low frequency", "cytosine. several low frequency neil1", "several low frequency neil1 polymorphisms", "frequency neil1 polymorphisms present", "neil1 polymorphisms present in", "polymorphisms present in about", "present in about 1% of", "in about 1% of general", "about 1% of general population", "1% of general population in", "of general population in the", "general population in the united", "population in the united states", "in the united states have", "the united states have been", "united states have been reported.", "states have been reported. different", "have been reported. different polymorphisms", "been reported. different polymorphisms have", "reported. different polymorphisms have different", "different polymorphisms have different effects", "polymorphisms have different effects on", "have different effects on neil1", "different effects on neil1 function", "on neil1 function and", "neil1 function and it", "function and it was", "and it was suggested that", "it was suggested that neil1", "was suggested that neil1 polymorphisms", "suggested that neil1 polymorphisms and", "that neil1 polymorphisms and neil1", "neil1 polymorphisms and neil1 deficiency", "polymorphisms and neil1 deficiency or", "and neil1 deficiency or haploinsuficiency", "neil1 deficiency or haploinsuficiency may", "deficiency or haploinsuficiency may be", "or haploinsuficiency may be involved", "haploinsuficiency may be involved in", "may be involved in predisposition", "be involved in predisposition to", "involved in predisposition to cancer", "in predisposition to cancer and", "predisposition to cancer and in", "to cancer and in metabolic", "cancer and in metabolic syndrome", "in metabolic syndrome roy", "metabolic syndrome roy et", "syndrome roy et al.", "et al. 2007 vartanian", "al. 2007 vartanian et", "2007 vartanian et al.", "et al. 2006 sampath", "al. 2006 sampath et", "2006 sampath et al.", "et al. 2011 prakash", "al. 2011 prakash et", "2011 prakash et al.", "prakash et al. 2014 .", "et al. 2014 . one", "al. 2014 . one polymorphism", ". one polymorphism neil1", "one polymorphism neil1 g83d", "neil1 g83d is associated", "g83d is associated with", "is associated with primary sclerosing", "associated with primary sclerosing cholangitis", "with primary sclerosing cholangitis and", "primary sclerosing cholangitis and cholangiocarcinoma", "cholangitis and cholangiocarcinoma forsbring", "and cholangiocarcinoma forsbring et", "cholangiocarcinoma forsbring et al.", "forsbring et al. 2009 .", "et al. 2009 . neil1", "al. 2009 . neil1 g83d", "2009 . neil1 g83d variant", ". neil1 g83d variant exhibits", "neil1 g83d variant exhibits impaired", "g83d variant exhibits impaired dna", "variant exhibits impaired dna glycosylase", "exhibits impaired dna glycosylase activity", "impaired dna glycosylase activity towards", "dna glycosylase activity towards different", "glycosylase activity towards different damaged", "activity towards different damaged dna", "towards different damaged dna bases", "damaged dna bases roy", "dna bases roy et", "bases roy et al.", "et al. 2007 prakash", "al. 2007 prakash et", "2007 prakash et al.", "et al. 2014 and", "al. 2014 and induces", "2014 and induces genomic", "induces genomic instability galick", "genomic instability galick et", "instability galick et al.", "galick et al. 2017 .
              neil1", "et al. 2017 .
              neil1 e28del", "2017 .
              neil1 e28del an", ".
              neil1 e28del an in", "e28del an in frame", "an in frame deletion variant", "in frame deletion variant of", "frame deletion variant of neil1", "deletion variant of neil1 reported", "variant of neil1 reported in", "of neil1 reported in gastric", "reported in gastric stomach", "gastric stomach cancer", "stomach cancer where", "cancer where glutamate at", "where glutamate at position 28", "glutamate at position 28 is", "at position 28 is deleted", "28 is deleted does", "is deleted does not", "deleted does not cleave", "does not cleave tg from", "not cleave tg from damaged", "cleave tg from damaged dna", "from damaged dna shinmura", "damaged dna shinmura et", "dna shinmura et al.", "shinmura et al. 2004 .
              neil1", "et al. 2004 .
              neil1 q282ter", "2004 .
              neil1 q282ter a", ".
              neil1 q282ter a neil1", "q282ter a neil1 variant", "a neil1 variant which lacks", "neil1 variant which lacks the", "variant which lacks the putative", "which lacks the putative nuclear", "lacks the putative nuclear localization", "the putative nuclear localization signal", "nuclear localization signal nls", "nls localizes to", "localizes to the cytosol and", "to the cytosol and is", "the cytosol and is therefore", "cytosol and is therefore not", "and is therefore not able", "is therefore not able to", "therefore not able to access", "not able to access damaged", "able to access damaged dna", "to access damaged dna substrates", "damaged dna substrates but", "dna substrates but its", "substrates but its involvement", "but its involvement in cancer", "its involvement in cancer is", "involvement in cancer is uncertain", "cancer is uncertain shinmura", "is uncertain shinmura et", "uncertain shinmura et al.", "shinmura et al. 2015 .
              reduced", "et al. 2015 .
              reduced expression", "al. 2015 .
              reduced expression of", "2015 .
              reduced expression of neil1", ".
              reduced expression of neil1 and", "expression of neil1 and neil2", "of neil1 and neil2 genes", "and neil2 genes accompanied", "neil2 genes accompanied with", "genes accompanied with increased", "accompanied with increased neil3 gene", "with increased neil3 gene expression", "increased neil3 gene expression was", "neil3 gene expression was detected", "gene expression was detected in", "expression was detected in various", "was detected in various cancers.", "detected in various cancers. neil1", "in various cancers. neil1 gene", "various cancers. neil1 gene silencing", "cancers. neil1 gene silencing by", "neil1 gene silencing by promoter", "gene silencing by promoter hypermethylation", "silencing by promoter hypermethylation may", "by promoter hypermethylation may be", "promoter hypermethylation may be one", "hypermethylation may be one of", "may be one of the", "be one of the underlying", "one of the underlying mechanisms", "of the underlying mechanisms for", "the underlying mechanisms for reduced", "underlying mechanisms for reduced neil1", "mechanisms for reduced neil1 expression", "for reduced neil1 expression in", "reduced neil1 expression in cancer", "expression in cancer shinmura", "in cancer shinmura et", "cancer shinmura et al.", "shinmura et al. 2016 .
              infection", "et al. 2016 .
              infection with", "al. 2016 .
              infection with the", "2016 .
              infection with the hepatitis", ".
              infection with the hepatitis c", "with the hepatitis c virus", "hepatitis c virus hcv", "virus hcv leads", "hcv leads to decreased", "leads to decreased neil1 expression", "to decreased neil1 expression in", "decreased neil1 expression in liver", "neil1 expression in liver cells", "in liver cells through", "liver cells through an", "cells through an unknown", "an unknown mechanism pal", "unknown mechanism pal et", "mechanism pal et al.", "pal et al. 2010 .
              mice", "et al. 2010 .
              mice that", "al. 2010 .
              mice that are", "2010 .
              mice that are double", ".
              mice that are double knockout", "that are double knockout for", "are double knockout for neil1", "double knockout for neil1 and", "knockout for neil1 and nthl1", "for neil1 and nthl1 genes", "neil1 and nthl1 genes accumulate", "and nthl1 genes accumulate dna", "nthl1 genes accumulate dna damage", "genes accumulate dna damage in", "accumulate dna damage in the", "dna damage in the form", "damage in the form of", "in the form of fapya", "the form of fapya and", "form of fapya and fapyg", "of fapya and fapyg and", "fapya and fapyg and are", "and fapyg and are more", "fapyg and are more prone", "and are more prone to", "are more prone to development", "more prone to development of", "prone to development of lung", "to development of lung adenocarcinoma", "development of lung adenocarcinoma than", "of lung adenocarcinoma than single", "lung adenocarcinoma than single neil1", "adenocarcinoma than single neil1 or", "than single neil1 or nthl1", "single neil1 or nthl1 gene", "neil1 or nthl1 gene knockouts", "nthl1 gene knockouts chan", "gene knockouts chan et", "knockouts chan et al.", "chan et al. 2009 .", "et al. 2009 . another", "al. 2009 . another study", "2009 . another study reported", ". another study reported that", "another study reported that neil1", "study reported that neil1 knockout", "reported that neil1 knockout mice", "that neil1 knockout mice did", "neil1 knockout mice did not", "knockout mice did not show", "mice did not show a", "did not show a predisposition", "not show a predisposition to", "show a predisposition to tumour", "a predisposition to tumour formation", "to tumour formation and", "tumour formation and neither", "formation and neither did", "and neither did double knockouts", "neither did double knockouts of", "did double knockouts of neil1", "double knockouts of neil1 and", "knockouts of neil1 and neil2", "neil1 and neil2 nor", "and neil2 nor triple", "neil2 nor triple knockouts", "nor triple knockouts of neil1", "knockouts of neil1 neil2", "of neil1 neil2 and", "neil1 neil2 and neil3.", "neil2 and neil3. neil1 knockout", "and neil3. neil1 knockout mice", "neil3. neil1 knockout mice are", "neil1 knockout mice are obese", "mice are obese consistent", "are obese consistent with", "obese consistent with the", "consistent with the metabolic syndrome", "the metabolic syndrome but", "metabolic syndrome but double", "syndrome but double knockouts", "but double knockouts of neil1", "of neil1 and neil2 do", "neil1 and neil2 do not", "and neil2 do not display", "neil2 do not display obesity", "not display obesity rolseth", "display obesity rolseth et", "obesity rolseth et al.", "rolseth et al. 2017 .
              " ] }, { "record_id": "GLY_000594_1_1829", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9629232", "r hsa", "hsa 9629232", "r hsa 9629232" ] }, { "record_id": "GLY_000594_1_1829", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective base", "base excision", "excision repair", "repair associated", "associated with", "with neil3", "defective base excision", "base excision repair", "excision repair associated", "repair associated with", "associated with neil3", "defective base excision repair", "base excision repair associated", "excision repair associated with", "repair associated with neil3", "defective base excision repair associated", "base excision repair associated with", "excision repair associated with neil3", "neil3 is", "is a", "a dna", "dna n", "n glycosylase", "glycosylase involved", "involved in", "in base", "the primary", "primary repair", "repair pathway", "pathway for", "for oxidative", "oxidative dna", "dna damage.", "damage. neil3", "neil3 can", "can detect", "detect and", "and remove", "remove oxidized", "oxidized guanine", "in the", "the form", "form of", "of 5", "5 guanidinohydatoin", "guanidinohydatoin and", "and spiroiminodihydantoin", "and oxidized", "oxidized thymine", "of thymine", "thymine glycol.", "glycol. neil3", "neil3 has", "has a", "a preference", "preference for", "for single", "single strand", "strand dna", "and is", "is implicated", "implicated in", "in repair", "repair of", "of oxidative", "dna damage", "damage at", "at telomeres", "zhou et", "et al.", "al. 2013", "2013 .", ". a", "a neil3", "neil3 disease", "disease variant", "variant neil3", "neil3 d132", "d132 is", "is unable", "unable to", "to cleave", "cleave 5", "5 guanidinohydantoin", "from oxidatively", "oxidatively damaged", "damaged dna.", "dna. individuals", "individuals harboring", "harboring a", "neil3 d132v", "d132v homozygous", "homozygous mutation", "mutation are", "are predisposed", "predisposed to", "to development", "development of", "of autoimmune", "autoimmune diseases", "massaad et", "al. 2016", "and neil3", "neil3 depletion", "depletion is", "is also", "also associated", "with an", "an increase", "increase in", "in telomere", "telomere damage", "damage and", "and loss", "al. 2017", "2017 .", ". neil3", "neil3 unhooks", "unhooks dna", "dna interstrand", "interstrand cross", "cross links", "during dna", "dna replication.", "replication. neil3", "neil3 resolves", "resolves psoralen", "and abasic", "abasic site", "site induced", "induced icls", "icls in", "in a", "a fanconi", "fanconi anemia", "pathway independent", "independent manner", "semlow et", "martin et", "2017 .
              a", ".
              a polymorphism", "polymorphism in", "in one", "one of", "of the", "the neil3", "neil3 gene", "gene splice", "splice sites", "sites may", "may increase", "increase the", "the risk", "risk of", "of myocardial", "myocardial infarction", "skarpengland et", "al. 2015", "2015 .", "neil3 expression", "expression in", "the heart", "heart increases", "increases after", "after heart", "heart failure", "failure in", "in humans", "humans and", "and after", "after myocardial", "infarction in", "in mouse", "mouse disease", "disease models.", "models. neil3", "neil3 knockout", "knockout mice", "mice show", "show increased", "increased mortality", "mortality after", "but there", "there is", "is no", "no increase", "the amount", "amount of", "of dna", "damage in", "in neil3", "knockout hearts.", "hearts. in", "neil3 may", "may function", "function in", "the epigenetic", "epigenetic regulation", "regulation of", "of gene", "gene expression", "expression and", "and facilitate", "facilitate transcriptional", "transcriptional response", "response to", "to myocardial", "olsen et", "neil3 mrna", "mrna expression", "expression is", "is increased", "increased in", "in human", "human carotid", "carotid plaques", "plaques and", "neil3 deficiency", "deficiency accelerates", "accelerates plaque", "plaque formation", "formation in", "in apoe", "apoe knockout", "but it", "it appears", "appears that", "that this", "this is", "is not", "not correlated", "correlated with", "with oxidative", "2016 .
              the", ".
              the function", "function of", "of neil3", "neil3 in", "in removal", "removal of", "of hydantoins", "hydantoins from", "from single", "dna may", "may be", "be important", "important for", "for removal", "of replication", "replication blocks", "blocks in", "in proliferating", "proliferating cells.", "cells. mouse", "mouse embryonic", "embryonic fibroblasts", "fibroblasts and", "and neuronal", "neuronal stem", "stem cell", "cell derived", "derived from", "from neil3", "knockout mouse", "mouse embryos", "embryos show", "show decreased", "decreased proliferation", "proliferation capacity", "capacity and", "and increased", "increased sensitivity", "sensitivity to", "to dna", "dna damaging", "damaging agents", "rolseth et", "be required", "required for", "for maintenance", "maintenance of", "of adult", "adult neurogenesis", "as neil3", "mice exhibit", "exhibit learning", "learning and", "and memory", "memory deficits", "deficits and", "and synaptic", "synaptic irregularities", "irregularities in", "the hippocampus", "regnell et", "al. 2012", "2012 .", ". in", "in addition", "neil3 deficient", "deficient neuronal", "stem cells", "cells exhibits", "exhibits signs", "signs of", "of premature", "premature senescence", "reis and", "and hermanson", "hermanson 2012", "show reduced", "reduced ability", "ability to", "to augment", "augment neurogenesis", "neurogenesis to", "to repair", "repair damage", "damage induced", "induced hypoxia", "hypoxia ischemia", "sejersted et", "al. 2011", "2011 .
              mice", ".
              mice that", "that are", "are triple", "triple knockout", "knockout for", "for neil1", "neil2 and", "neil3 do", "do not", "not show", "show a", "a predisposition", "predisposition to", "to tumour", "tumour formation", "formation or", "or changes", "changes in", "telomere length", "2017 .
              ", "neil3 is a", "is a dna", "a dna n", "dna n glycosylase", "n glycosylase involved", "glycosylase involved in", "involved in base", "in base excision", "repair ber", "the primary repair", "primary repair pathway", "repair pathway for", "pathway for oxidative", "for oxidative dna", "oxidative dna damage.", "dna damage. neil3", "damage. neil3 can", "neil3 can detect", "can detect and", "detect and remove", "and remove oxidized", "remove oxidized guanine", "guanine in", "in the form", "the form of", "form of 5", "of 5 guanidinohydatoin", "5 guanidinohydatoin and", "guanidinohydatoin and spiroiminodihydantoin", "spiroiminodihydantoin and", "and oxidized thymine", "thymine in", "form of thymine", "of thymine glycol.", "thymine glycol. neil3", "glycol. neil3 has", "neil3 has a", "has a preference", "a preference for", "preference for single", "for single strand", "single strand dna", "dna ssdna", "ssdna and", "and is implicated", "is implicated in", "implicated in repair", "in repair of", "repair of oxidative", "of oxidative dna", "oxidative dna damage", "dna damage at", "damage at telomeres", "telomeres zhou", "zhou et al.", "et al. 2013", "al. 2013 .", "2013 . a", ". a neil3", "a neil3 disease", "neil3 disease variant", "disease variant neil3", "variant neil3 d132", "neil3 d132 is", "d132 is unable", "is unable to", "unable to cleave", "to cleave 5", "cleave 5 guanidinohydantoin", "guanidinohydantoin gh", "gh from", "from oxidatively damaged", "oxidatively damaged dna.", "damaged dna. individuals", "dna. individuals harboring", "individuals harboring a", "harboring a neil3", "a neil3 d132v", "neil3 d132v homozygous", "d132v homozygous mutation", "homozygous mutation are", "mutation are predisposed", "are predisposed to", "predisposed to development", "to development of", "development of autoimmune", "of autoimmune diseases", "diseases massaad", "massaad et al.", "et al. 2016", "2016 and", "and neil3 depletion", "neil3 depletion is", "depletion is also", "is also associated", "also associated with", "associated with an", "with an increase", "an increase in", "increase in telomere", "in telomere damage", "telomere damage and", "damage and loss", "loss zhou", "et al. 2017", "al. 2017 .", "2017 . neil3", ". neil3 unhooks", "neil3 unhooks dna", "unhooks dna interstrand", "dna interstrand cross", "interstrand cross links", "links icls", "icls during", "during dna replication.", "dna replication. neil3", "replication. neil3 resolves", "neil3 resolves psoralen", "psoralen and", "and abasic site", "abasic site induced", "site induced icls", "induced icls in", "icls in a", "in a fanconi", "a fanconi anemia", "anemia fa", "fa pathway", "pathway independent manner", "manner semlow", "semlow et al.", "2016 martin", "martin et al.", "al. 2017 .
              a", "2017 .
              a polymorphism", ".
              a polymorphism in", "polymorphism in one", "in one of", "one of the", "of the neil3", "the neil3 gene", "neil3 gene splice", "gene splice sites", "splice sites may", "sites may increase", "may increase the", "increase the risk", "the risk of", "risk of myocardial", "of myocardial infarction", "infarction skarpengland", "skarpengland et al.", "et al. 2015", "al. 2015 .", "2015 . neil3", ". neil3 expression", "neil3 expression in", "expression in the", "in the heart", "the heart increases", "heart increases after", "increases after heart", "after heart failure", "heart failure in", "failure in humans", "in humans and", "humans and after", "and after myocardial", "after myocardial infarction", "myocardial infarction in", "infarction in mouse", "in mouse disease", "mouse disease models.", "disease models. neil3", "models. neil3 knockout", "neil3 knockout mice", "knockout mice show", "mice show increased", "show increased mortality", "increased mortality after", "mortality after myocardial", "infarction but", "but there is", "there is no", "is no increase", "no increase in", "increase in the", "in the amount", "the amount of", "amount of dna", "of dna damage", "dna damage in", "damage in neil3", "in neil3 knockout", "neil3 knockout hearts.", "knockout hearts. in", "hearts. in the", "heart neil3", "neil3 may function", "may function in", "function in the", "in the epigenetic", "the epigenetic regulation", "epigenetic regulation of", "regulation of gene", "of gene expression", "gene expression and", "expression and facilitate", "and facilitate transcriptional", "facilitate transcriptional response", "transcriptional response to", "response to myocardial", "to myocardial infarction", "infarction olsen", "olsen et al.", ". neil3 mrna", "neil3 mrna expression", "mrna expression is", "expression is increased", "is increased in", "increased in human", "in human carotid", "human carotid plaques", "carotid plaques and", "plaques and neil3", "and neil3 deficiency", "neil3 deficiency accelerates", "deficiency accelerates plaque", "accelerates plaque formation", "plaque formation in", "formation in apoe", "in apoe knockout", "apoe knockout mice", "mice but", "but it appears", "it appears that", "appears that this", "that this is", "this is not", "is not correlated", "not correlated with", "correlated with oxidative", "with oxidative dna", "damage skarpengland", "al. 2016 .
              the", "2016 .
              the function", ".
              the function of", "function of neil3", "of neil3 in", "neil3 in removal", "in removal of", "removal of hydantoins", "of hydantoins from", "hydantoins from single", "from single strand", "strand dna may", "dna may be", "may be important", "be important for", "important for removal", "for removal of", "removal of replication", "of replication blocks", "replication blocks in", "blocks in proliferating", "in proliferating cells.", "proliferating cells. mouse", "cells. mouse embryonic", "mouse embryonic fibroblasts", "embryonic fibroblasts and", "fibroblasts and neuronal", "and neuronal stem", "neuronal stem cell", "stem cell derived", "cell derived from", "derived from neil3", "from neil3 knockout", "neil3 knockout mouse", "knockout mouse embryos", "mouse embryos show", "embryos show decreased", "show decreased proliferation", "decreased proliferation capacity", "proliferation capacity and", "capacity and increased", "and increased sensitivity", "increased sensitivity to", "sensitivity to dna", "to dna damaging", "dna damaging agents", "agents rolseth", "rolseth et al.", "2013 . neil3", ". neil3 may", "neil3 may be", "may be required", "be required for", "required for maintenance", "for maintenance of", "maintenance of adult", "of adult neurogenesis", "neurogenesis as", "as neil3 knockout", "knockout mice exhibit", "mice exhibit learning", "exhibit learning and", "learning and memory", "and memory deficits", "memory deficits and", "deficits and synaptic", "and synaptic irregularities", "synaptic irregularities in", "irregularities in the", "in the hippocampus", "hippocampus regnell", "regnell et al.", "et al. 2012", "al. 2012 .", "2012 . in", ". in addition", "addition neil3", "neil3 deficient neuronal", "deficient neuronal stem", "neuronal stem cells", "stem cells exhibits", "cells exhibits signs", "exhibits signs of", "signs of premature", "of premature senescence", "senescence reis", "reis and hermanson", "and hermanson 2012", "2012 and", "and neil3 knockout", "mice show reduced", "show reduced ability", "reduced ability to", "ability to augment", "to augment neurogenesis", "augment neurogenesis to", "neurogenesis to repair", "to repair damage", "repair damage induced", "damage induced hypoxia", "induced hypoxia ischemia", "ischemia sejersted", "sejersted et al.", "et al. 2011", "al. 2011 .
              mice", "2011 .
              mice that", ".
              mice that are", "that are triple", "are triple knockout", "triple knockout for", "knockout for neil1", "neil1 neil2", "neil2 and neil3", "and neil3 do", "neil3 do not", "do not show", "not show a", "show a predisposition", "a predisposition to", "predisposition to tumour", "to tumour formation", "tumour formation or", "formation or changes", "or changes in", "changes in telomere", "in telomere length", "length rolseth", "al. 2017 .
              ", "neil3 is a dna", "is a dna n", "a dna n glycosylase", "dna n glycosylase involved", "n glycosylase involved in", "glycosylase involved in base", "involved in base excision", "in base excision repair", "excision repair ber", "ber the", "the primary repair pathway", "primary repair pathway for", "repair pathway for oxidative", "pathway for oxidative dna", "for oxidative dna damage.", "oxidative dna damage. neil3", "dna damage. neil3 can", "damage. neil3 can detect", "neil3 can detect and", "can detect and remove", "detect and remove oxidized", "and remove oxidized guanine", "oxidized guanine in", "guanine in the", "in the form of", "the form of 5", "form of 5 guanidinohydatoin", "of 5 guanidinohydatoin and", "5 guanidinohydatoin and spiroiminodihydantoin", "and spiroiminodihydantoin and", "spiroiminodihydantoin and oxidized", "oxidized thymine in", "thymine in the", "the form of thymine", "form of thymine glycol.", "of thymine glycol. neil3", "thymine glycol. neil3 has", "glycol. neil3 has a", "neil3 has a preference", "has a preference for", "a preference for single", "preference for single strand", "for single strand dna", "strand dna ssdna", "ssdna and is", "and is implicated in", "is implicated in repair", "implicated in repair of", "in repair of oxidative", "repair of oxidative dna", "of oxidative dna damage", "oxidative dna damage at", "dna damage at telomeres", "at telomeres zhou", "telomeres zhou et", "zhou et al. 2013", "et al. 2013 .", "al. 2013 . a", "2013 . a neil3", ". a neil3 disease", "a neil3 disease variant", "neil3 disease variant neil3", "disease variant neil3 d132", "variant neil3 d132 is", "neil3 d132 is unable", "d132 is unable to", "is unable to cleave", "unable to cleave 5", "to cleave 5 guanidinohydantoin", "5 guanidinohydantoin gh", "gh from oxidatively", "from oxidatively damaged dna.", "oxidatively damaged dna. individuals", "damaged dna. individuals harboring", "dna. individuals harboring a", "individuals harboring a neil3", "harboring a neil3 d132v", "a neil3 d132v homozygous", "neil3 d132v homozygous mutation", "d132v homozygous mutation are", "homozygous mutation are predisposed", "mutation are predisposed to", "are predisposed to development", "predisposed to development of", "to development of autoimmune", "development of autoimmune diseases", "autoimmune diseases massaad", "diseases massaad et", "massaad et al. 2016", "al. 2016 and", "2016 and neil3", "and neil3 depletion is", "neil3 depletion is also", "depletion is also associated", "is also associated with", "also associated with an", "associated with an increase", "with an increase in", "an increase in telomere", "increase in telomere damage", "in telomere damage and", "telomere damage and loss", "and loss zhou", "loss zhou et", "zhou et al. 2017", "et al. 2017 .", "al. 2017 . neil3", "2017 . neil3 unhooks", ". neil3 unhooks dna", "neil3 unhooks dna interstrand", "unhooks dna interstrand cross", "dna interstrand cross links", "cross links icls", "icls during dna", "during dna replication. neil3", "dna replication. neil3 resolves", "replication. neil3 resolves psoralen", "resolves psoralen and", "psoralen and abasic", "and abasic site induced", "abasic site induced icls", "site induced icls in", "induced icls in a", "icls in a fanconi", "in a fanconi anemia", "fanconi anemia fa", "fa pathway independent", "independent manner semlow", "manner semlow et", "semlow et al. 2016", "al. 2016 martin", "2016 martin et", "martin et al. 2017", "et al. 2017 .
              a", "al. 2017 .
              a polymorphism", "2017 .
              a polymorphism in", ".
              a polymorphism in one", "polymorphism in one of", "in one of the", "one of the neil3", "of the neil3 gene", "the neil3 gene splice", "neil3 gene splice sites", "gene splice sites may", "splice sites may increase", "sites may increase the", "may increase the risk", "increase the risk of", "the risk of myocardial", "risk of myocardial infarction", "myocardial infarction skarpengland", "infarction skarpengland et", "skarpengland et al. 2015", "et al. 2015 .", "al. 2015 . neil3", "2015 . neil3 expression", ". neil3 expression in", "neil3 expression in the", "expression in the heart", "in the heart increases", "the heart increases after", "heart increases after heart", "increases after heart failure", "after heart failure in", "heart failure in humans", "failure in humans and", "in humans and after", "humans and after myocardial", "and after myocardial infarction", "after myocardial infarction in", "myocardial infarction in mouse", "infarction in mouse disease", "in mouse disease models.", "mouse disease models. neil3", "disease models. neil3 knockout", "models. neil3 knockout mice", "neil3 knockout mice show", "knockout mice show increased", "mice show increased mortality", "show increased mortality after", "increased mortality after myocardial", "mortality after myocardial infarction", "myocardial infarction but", "infarction but there", "but there is no", "there is no increase", "is no increase in", "no increase in the", "increase in the amount", "in the amount of", "the amount of dna", "amount of dna damage", "of dna damage in", "dna damage in neil3", "damage in neil3 knockout", "in neil3 knockout hearts.", "neil3 knockout hearts. in", "knockout hearts. in the", "hearts. in the heart", "the heart neil3", "heart neil3 may", "neil3 may function in", "may function in the", "function in the epigenetic", "in the epigenetic regulation", "the epigenetic regulation of", "epigenetic regulation of gene", "regulation of gene expression", "of gene expression and", "gene expression and facilitate", "expression and facilitate transcriptional", "and facilitate transcriptional response", "facilitate transcriptional response to", "transcriptional response to myocardial", "response to myocardial infarction", "myocardial infarction olsen", "infarction olsen et", "olsen et al. 2017", "2017 . neil3 mrna", ". neil3 mrna expression", "neil3 mrna expression is", "mrna expression is increased", "expression is increased in", "is increased in human", "increased in human carotid", "in human carotid plaques", "human carotid plaques and", "carotid plaques and neil3", "plaques and neil3 deficiency", "and neil3 deficiency accelerates", "neil3 deficiency accelerates plaque", "deficiency accelerates plaque formation", "accelerates plaque formation in", "plaque formation in apoe", "formation in apoe knockout", "in apoe knockout mice", "knockout mice but", "mice but it", "but it appears that", "it appears that this", "appears that this is", "that this is not", "this is not correlated", "is not correlated with", "not correlated with oxidative", "correlated with oxidative dna", "with oxidative dna damage", "dna damage skarpengland", "damage skarpengland et", "skarpengland et al. 2016", "et al. 2016 .
              the", "al. 2016 .
              the function", "2016 .
              the function of", ".
              the function of neil3", "function of neil3 in", "of neil3 in removal", "neil3 in removal of", "in removal of hydantoins", "removal of hydantoins from", "of hydantoins from single", "hydantoins from single strand", "from single strand dna", "single strand dna may", "strand dna may be", "dna may be important", "may be important for", "be important for removal", "important for removal of", "for removal of replication", "removal of replication blocks", "of replication blocks in", "replication blocks in proliferating", "blocks in proliferating cells.", "in proliferating cells. mouse", "proliferating cells. mouse embryonic", "cells. mouse embryonic fibroblasts", "mouse embryonic fibroblasts and", "embryonic fibroblasts and neuronal", "fibroblasts and neuronal stem", "and neuronal stem cell", "neuronal stem cell derived", "stem cell derived from", "cell derived from neil3", "derived from neil3 knockout", "from neil3 knockout mouse", "neil3 knockout mouse embryos", "knockout mouse embryos show", "mouse embryos show decreased", "embryos show decreased proliferation", "show decreased proliferation capacity", "decreased proliferation capacity and", "proliferation capacity and increased", "capacity and increased sensitivity", "and increased sensitivity to", "increased sensitivity to dna", "sensitivity to dna damaging", "to dna damaging agents", "damaging agents rolseth", "agents rolseth et", "rolseth et al. 2013", "al. 2013 . neil3", "2013 . neil3 may", ". neil3 may be", "neil3 may be required", "may be required for", "be required for maintenance", "required for maintenance of", "for maintenance of adult", "maintenance of adult neurogenesis", "adult neurogenesis as", "neurogenesis as neil3", "as neil3 knockout mice", "neil3 knockout mice exhibit", "knockout mice exhibit learning", "mice exhibit learning and", "exhibit learning and memory", "learning and memory deficits", "and memory deficits and", "memory deficits and synaptic", "deficits and synaptic irregularities", "and synaptic irregularities in", "synaptic irregularities in the", "irregularities in the hippocampus", "the hippocampus regnell", "hippocampus regnell et", "regnell et al. 2012", "et al. 2012 .", "al. 2012 . in", "2012 . in addition", "in addition neil3", "addition neil3 deficient", "neil3 deficient neuronal stem", "deficient neuronal stem cells", "neuronal stem cells exhibits", "stem cells exhibits signs", "cells exhibits signs of", "exhibits signs of premature", "signs of premature senescence", "premature senescence reis", "senescence reis and", "reis and hermanson 2012", "hermanson 2012 and", "2012 and neil3", "and neil3 knockout mice", "knockout mice show reduced", "mice show reduced ability", "show reduced ability to", "reduced ability to augment", "ability to augment neurogenesis", "to augment neurogenesis to", "augment neurogenesis to repair", "neurogenesis to repair damage", "to repair damage induced", "repair damage induced hypoxia", "damage induced hypoxia ischemia", "hypoxia ischemia sejersted", "ischemia sejersted et", "sejersted et al. 2011", "et al. 2011 .
              mice", "al. 2011 .
              mice that", "2011 .
              mice that are", ".
              mice that are triple", "that are triple knockout", "are triple knockout for", "triple knockout for neil1", "for neil1 neil2", "neil1 neil2 and", "neil2 and neil3 do", "and neil3 do not", "neil3 do not show", "do not show a", "not show a predisposition", "show a predisposition to", "a predisposition to tumour", "predisposition to tumour formation", "to tumour formation or", "tumour formation or changes", "formation or changes in", "or changes in telomere", "changes in telomere length", "telomere length rolseth", "length rolseth et", "rolseth et al. 2017", "et al. 2017 .
              ", "neil3 is a dna n", "is a dna n glycosylase", "a dna n glycosylase involved", "dna n glycosylase involved in", "n glycosylase involved in base", "glycosylase involved in base excision", "involved in base excision repair", "base excision repair ber", "ber the primary", "the primary repair pathway for", "primary repair pathway for oxidative", "repair pathway for oxidative dna", "pathway for oxidative dna damage.", "for oxidative dna damage. neil3", "oxidative dna damage. neil3 can", "dna damage. neil3 can detect", "damage. neil3 can detect and", "neil3 can detect and remove", "can detect and remove oxidized", "detect and remove oxidized guanine", "remove oxidized guanine in", "oxidized guanine in the", "guanine in the form", "in the form of 5", "the form of 5 guanidinohydatoin", "form of 5 guanidinohydatoin and", "of 5 guanidinohydatoin and spiroiminodihydantoin", "guanidinohydatoin and spiroiminodihydantoin and", "and spiroiminodihydantoin and oxidized", "spiroiminodihydantoin and oxidized thymine", "and oxidized thymine in", "oxidized thymine in the", "thymine in the form", "in the form of thymine", "the form of thymine glycol.", "form of thymine glycol. neil3", "of thymine glycol. neil3 has", "thymine glycol. neil3 has a", "glycol. neil3 has a preference", "neil3 has a preference for", "has a preference for single", "a preference for single strand", "preference for single strand dna", "single strand dna ssdna", "dna ssdna and", "ssdna and is implicated", "and is implicated in repair", "is implicated in repair of", "implicated in repair of oxidative", "in repair of oxidative dna", "repair of oxidative dna damage", "of oxidative dna damage at", "oxidative dna damage at telomeres", "damage at telomeres zhou", "at telomeres zhou et", "telomeres zhou et al.", "zhou et al. 2013 .", "et al. 2013 . a", "al. 2013 . a neil3", "2013 . a neil3 disease", ". a neil3 disease variant", "a neil3 disease variant neil3", "neil3 disease variant neil3 d132", "disease variant neil3 d132 is", "variant neil3 d132 is unable", "neil3 d132 is unable to", "d132 is unable to cleave", "is unable to cleave 5", "unable to cleave 5 guanidinohydantoin", "cleave 5 guanidinohydantoin gh", "guanidinohydantoin gh from", "gh from oxidatively damaged", "from oxidatively damaged dna. individuals", "oxidatively damaged dna. individuals harboring", "damaged dna. individuals harboring a", "dna. individuals harboring a neil3", "individuals harboring a neil3 d132v", "harboring a neil3 d132v homozygous", "a neil3 d132v homozygous mutation", "neil3 d132v homozygous mutation are", "d132v homozygous mutation are predisposed", "homozygous mutation are predisposed to", "mutation are predisposed to development", "are predisposed to development of", "predisposed to development of autoimmune", "to development of autoimmune diseases", "of autoimmune diseases massaad", "autoimmune diseases massaad et", "diseases massaad et al.", "et al. 2016 and", "al. 2016 and neil3", "2016 and neil3 depletion", "and neil3 depletion is also", "neil3 depletion is also associated", "depletion is also associated with", "is also associated with an", "also associated with an increase", "associated with an increase in", "with an increase in telomere", "an increase in telomere damage", "increase in telomere damage and", "in telomere damage and loss", "damage and loss zhou", "and loss zhou et", "loss zhou et al.", "zhou et al. 2017 .", "et al. 2017 . neil3", "al. 2017 . neil3 unhooks", "2017 . neil3 unhooks dna", ". neil3 unhooks dna interstrand", "neil3 unhooks dna interstrand cross", "unhooks dna interstrand cross links", "interstrand cross links icls", "links icls during", "icls during dna replication.", "during dna replication. neil3 resolves", "dna replication. neil3 resolves psoralen", "neil3 resolves psoralen and", "resolves psoralen and abasic", "psoralen and abasic site", "and abasic site induced icls", "abasic site induced icls in", "site induced icls in a", "induced icls in a fanconi", "icls in a fanconi anemia", "a fanconi anemia fa", "anemia fa pathway", "fa pathway independent manner", "pathway independent manner semlow", "independent manner semlow et", "manner semlow et al.", "et al. 2016 martin", "al. 2016 martin et", "2016 martin et al.", "martin et al. 2017 .
              a", "et al. 2017 .
              a polymorphism", "al. 2017 .
              a polymorphism in", "2017 .
              a polymorphism in one", ".
              a polymorphism in one of", "polymorphism in one of the", "in one of the neil3", "one of the neil3 gene", "of the neil3 gene splice", "the neil3 gene splice sites", "neil3 gene splice sites may", "gene splice sites may increase", "splice sites may increase the", "sites may increase the risk", "may increase the risk of", "increase the risk of myocardial", "the risk of myocardial infarction", "of myocardial infarction skarpengland", "myocardial infarction skarpengland et", "infarction skarpengland et al.", "skarpengland et al. 2015 .", "et al. 2015 . neil3", "al. 2015 . neil3 expression", "2015 . neil3 expression in", ". neil3 expression in the", "neil3 expression in the heart", "expression in the heart increases", "in the heart increases after", "the heart increases after heart", "heart increases after heart failure", "increases after heart failure in", "after heart failure in humans", "heart failure in humans and", "failure in humans and after", "in humans and after myocardial", "humans and after myocardial infarction", "and after myocardial infarction in", "after myocardial infarction in mouse", "myocardial infarction in mouse disease", "infarction in mouse disease models.", "in mouse disease models. neil3", "mouse disease models. neil3 knockout", "disease models. neil3 knockout mice", "models. neil3 knockout mice show", "neil3 knockout mice show increased", "knockout mice show increased mortality", "mice show increased mortality after", "show increased mortality after myocardial", "increased mortality after myocardial infarction", "after myocardial infarction but", "myocardial infarction but there", "infarction but there is", "but there is no increase", "there is no increase in", "is no increase in the", "no increase in the amount", "increase in the amount of", "in the amount of dna", "the amount of dna damage", "amount of dna damage in", "of dna damage in neil3", "dna damage in neil3 knockout", "damage in neil3 knockout hearts.", "in neil3 knockout hearts. in", "neil3 knockout hearts. in the", "knockout hearts. in the heart", "in the heart neil3", "the heart neil3 may", "heart neil3 may function", "neil3 may function in the", "may function in the epigenetic", "function in the epigenetic regulation", "in the epigenetic regulation of", "the epigenetic regulation of gene", "epigenetic regulation of gene expression", "regulation of gene expression and", "of gene expression and facilitate", "gene expression and facilitate transcriptional", "expression and facilitate transcriptional response", "and facilitate transcriptional response to", "facilitate transcriptional response to myocardial", "transcriptional response to myocardial infarction", "to myocardial infarction olsen", "myocardial infarction olsen et", "infarction olsen et al.", "olsen et al. 2017 .", "al. 2017 . neil3 mrna", "2017 . neil3 mrna expression", ". neil3 mrna expression is", "neil3 mrna expression is increased", "mrna expression is increased in", "expression is increased in human", "is increased in human carotid", "increased in human carotid plaques", "in human carotid plaques and", "human carotid plaques and neil3", "carotid plaques and neil3 deficiency", "plaques and neil3 deficiency accelerates", "and neil3 deficiency accelerates plaque", "neil3 deficiency accelerates plaque formation", "deficiency accelerates plaque formation in", "accelerates plaque formation in apoe", "plaque formation in apoe knockout", "formation in apoe knockout mice", "apoe knockout mice but", "knockout mice but it", "mice but it appears", "but it appears that this", "it appears that this is", "appears that this is not", "that this is not correlated", "this is not correlated with", "is not correlated with oxidative", "not correlated with oxidative dna", "correlated with oxidative dna damage", "oxidative dna damage skarpengland", "dna damage skarpengland et", "damage skarpengland et al.", "skarpengland et al. 2016 .
              the", "et al. 2016 .
              the function", "al. 2016 .
              the function of", "2016 .
              the function of neil3", ".
              the function of neil3 in", "function of neil3 in removal", "of neil3 in removal of", "neil3 in removal of hydantoins", "in removal of hydantoins from", "removal of hydantoins from single", "of hydantoins from single strand", "hydantoins from single strand dna", "from single strand dna may", "single strand dna may be", "strand dna may be important", "dna may be important for", "may be important for removal", "be important for removal of", "important for removal of replication", "for removal of replication blocks", "removal of replication blocks in", "of replication blocks in proliferating", "replication blocks in proliferating cells.", "blocks in proliferating cells. mouse", "in proliferating cells. mouse embryonic", "proliferating cells. mouse embryonic fibroblasts", "cells. mouse embryonic fibroblasts and", "mouse embryonic fibroblasts and neuronal", "embryonic fibroblasts and neuronal stem", "fibroblasts and neuronal stem cell", "and neuronal stem cell derived", "neuronal stem cell derived from", "stem cell derived from neil3", "cell derived from neil3 knockout", "derived from neil3 knockout mouse", "from neil3 knockout mouse embryos", "neil3 knockout mouse embryos show", "knockout mouse embryos show decreased", "mouse embryos show decreased proliferation", "embryos show decreased proliferation capacity", "show decreased proliferation capacity and", "decreased proliferation capacity and increased", "proliferation capacity and increased sensitivity", "capacity and increased sensitivity to", "and increased sensitivity to dna", "increased sensitivity to dna damaging", "sensitivity to dna damaging agents", "dna damaging agents rolseth", "damaging agents rolseth et", "agents rolseth et al.", "rolseth et al. 2013 .", "et al. 2013 . neil3", "al. 2013 . neil3 may", "2013 . neil3 may be", ". neil3 may be required", "neil3 may be required for", "may be required for maintenance", "be required for maintenance of", "required for maintenance of adult", "for maintenance of adult neurogenesis", "of adult neurogenesis as", "adult neurogenesis as neil3", "neurogenesis as neil3 knockout", "as neil3 knockout mice exhibit", "neil3 knockout mice exhibit learning", "knockout mice exhibit learning and", "mice exhibit learning and memory", "exhibit learning and memory deficits", "learning and memory deficits and", "and memory deficits and synaptic", "memory deficits and synaptic irregularities", "deficits and synaptic irregularities in", "and synaptic irregularities in the", "synaptic irregularities in the hippocampus", "in the hippocampus regnell", "the hippocampus regnell et", "hippocampus regnell et al.", "regnell et al. 2012 .", "et al. 2012 . in", "al. 2012 . in addition", ". in addition neil3", "in addition neil3 deficient", "addition neil3 deficient neuronal", "neil3 deficient neuronal stem cells", "deficient neuronal stem cells exhibits", "neuronal stem cells exhibits signs", "stem cells exhibits signs of", "cells exhibits signs of premature", "exhibits signs of premature senescence", "of premature senescence reis", "premature senescence reis and", "senescence reis and hermanson", "and hermanson 2012 and", "hermanson 2012 and neil3", "2012 and neil3 knockout", "and neil3 knockout mice show", "neil3 knockout mice show reduced", "knockout mice show reduced ability", "mice show reduced ability to", "show reduced ability to augment", "reduced ability to augment neurogenesis", "ability to augment neurogenesis to", "to augment neurogenesis to repair", "augment neurogenesis to repair damage", "neurogenesis to repair damage induced", "to repair damage induced hypoxia", "repair damage induced hypoxia ischemia", "induced hypoxia ischemia sejersted", "hypoxia ischemia sejersted et", "ischemia sejersted et al.", "sejersted et al. 2011 .
              mice", "et al. 2011 .
              mice that", "al. 2011 .
              mice that are", "2011 .
              mice that are triple", ".
              mice that are triple knockout", "that are triple knockout for", "are triple knockout for neil1", "knockout for neil1 neil2", "for neil1 neil2 and", "neil1 neil2 and neil3", "neil2 and neil3 do not", "and neil3 do not show", "neil3 do not show a", "do not show a predisposition", "not show a predisposition to", "show a predisposition to tumour", "a predisposition to tumour formation", "predisposition to tumour formation or", "to tumour formation or changes", "tumour formation or changes in", "formation or changes in telomere", "or changes in telomere length", "in telomere length rolseth", "telomere length rolseth et", "length rolseth et al.", "rolseth et al. 2017 .
              " ] }, { "record_id": "GLY_000594_1_1830", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9630221", "r hsa", "hsa 9630221", "r hsa 9630221" ] }, { "record_id": "GLY_000594_1_1830", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective nthl1", "nthl1 substrate", "substrate processing", "defective nthl1 substrate", "nthl1 substrate processing", "defective nthl1 substrate processing", "nthl1 d239y", "d239y is", "is produced", "produced as", "as a", "a consequence", "consequence of", "of a", "a single", "single nucleotide", "nucleotide polymorphism", "rs3087468 in", "in the", "the nthl1", "nthl1 gene.", "gene. the", "the frequency", "frequency of", "of this", "this polymorphism", "polymorphism varies", "varies in", "in different", "different populations.", "populations. substitution", "substitution of", "of aspartic", "aspartic acid", "acid residue", "residue at", "at position", 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"and multiple", "multiple other", "other types", "types of", "of cancer", "and benign", "benign tumors", "weren et", "et al.", "al. 2015", "rivera et", "grolleman et", "al. 2019", "2019 .", ". apart", "apart from", "from nthl1", "at least", "least seven", "seven other", "other truncating", "truncating variants", "variants have", "been identified", "identified in", "in patients", "patients with", "with nthl1", "such as", "as nthl1", "nthl1 a79fs", "nthl1 ala79fs", "nthl1 y130ter", "nthl1 tyr130*", "nthl1 w182ter", "nthl1 trp182*", "nthl1 c.709+1g>a", "nthl1 i245fs", "nthl1 ile245fs", "nthl1 w269ter", "nthl1 trp269*", "nthl1 q287ter", "nthl1 gln287*", "broderick et", "al. 2017", "several different mutations", "different mutations that", "mutations that result", "that result in", "result in truncation", "in truncation of", "truncation of nthl1", "of nthl1 protein", "nthl1 protein have", "protein have been", "have been described", "been described and", "described and associated", "and 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intact", "in about", "about 30%", "30% of", "of melanoma", "melanoma cases", "cases with", "with genomic", "genomic deletions", "deletions involving", "involving the", "cdkn2a locus", "freedberg et", "al. 2008", "2008 .", ". several", "several different", "different familial", "melanoma germline", "germline mutations", "mutations map", "the exon", "1beta splice", "splice donor", "donor site", "harland et", "al. 2005", "2005 .
              the", ".
              the ability", "ability of", "to localize", "localize to", "the nucleolus", "nucleolus also", "also plays", "plays a", "a role", "role in", "in p14arf", "p14arf mediated", "mediated stabilization", "stabilization of", "of p53.", "p53. mutations", "mutations in", "exon 2", "2 of", "gene can", "can lead", "lead to", "to missense", "missense mutations", "p14arf that", "that affect", "affect its", "its nucleolar", "nucleolar localization", "localization and", "and p53", "but the", "the exact", "exact mechanism", "mechanism has", "has not", "not been", "been fully", "fully elucidated", "zhang and", "and xiong", "xiong 1999", "reviewed by", "by fontana", "fontana et", "al. 2019", "2019 .", "in cell culture", "culture p14arf", "p14arf cdkn2a", "cdkn2a transcript 4", "4 cdkn2a", "4 arf", "one of the", "of the two", "the two main", "two main protein", "main protein products", "protein products of", "products of the", "of the cdkn2a", "the cdkn2a gene", "gene contributes", 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responsible", "responsible for a", "for a familial", "a familial melanoma", "familial melanoma syndrome", "melanoma syndrome in", "syndrome in which", "in which the", "which the p16ink4a", "the p16ink4a product", "p16ink4a product of", "product of the", "cdkn2a gene is", "gene is unaffected.", "is unaffected. this", "unaffected. this mutation", "this mutation is", "mutation is rare", "is rare and", "rare and has", "and has so", "has so far", "so far been", "far been reported", "been reported in", "reported in one", "in one family", "one family only.", "family only. the", "only. the mutant", "the mutant protein", "protein p14arf", "p14arf v22pfs*46 has", "v22pfs*46 has the", "has the nucleotide", "the nucleotide localization", "nucleotide localization signal", "and the n", "the n terminal", "n terminal mdm2", "terminal mdm2 interaction", "mdm2 interaction region", "interaction region preserved", "preserved but", "but is unable", "is unable to", "unable to translocate", "to translocate from", "translocate from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the nucleus", "nucleus possibly", "possibly due to", "due to aberrant", "to aberrant conformation", "conformation rizos", "rizos puig", "puig et al.", "et al. 2001", "and also lacks", "also lacks the", "lacks the c", "the c terminal", "c terminal mdm2", "mdm2 interaction region.", "interaction region. relocation", "region. relocation of", "relocation of wild", "of wild type", "wild type p14arf", "type p14arf to", "p14arf to the", "to the cytosol", "the cytosol has", "cytosol has been", "has been observed", "been observed in", "observed in melanoma", "melanoma rizos", "rizos darmanian", "darmanian et al.", "2001 and", "and aggressive thyroid", "aggressive thyroid papillary", "thyroid papillary carcinoma", "carcinoma ferru", "ferru et al.", "et al. 2006", "al. 2006 .", "2006 . genomic", ". genomic deletion", "genomic deletion of", "deletion of exon", "of exon 1beta", "1beta with", "with exons 1alpha", "1alpha 2", "2 and 3", "and 3 intact", "intact has", "has been reported", "reported in about", "in about 30%", "about 30% of", "30% of melanoma", "of melanoma cases", "melanoma cases with", "cases with genomic", "with genomic deletions", "genomic deletions involving", "deletions involving the", "involving the cdkn2a", "the cdkn2a locus", "locus freedberg", "freedberg et al.", "et al. 2008", "al. 2008 .", "2008 . several", ". several different", "several different familial", "different familial melanoma", "familial melanoma germline", "melanoma germline mutations", "germline mutations map", "mutations map to", "to the exon", "the exon 1beta", "exon 1beta splice", "1beta splice donor", "splice donor site", "site harland", "harland et al.", "et al. 2005", "al. 2005 .
              the", "2005 .
              the ability", ".
              the ability of", "ability of p14arf", "of p14arf to", "p14arf to localize", "to localize to", "localize to the", "to the nucleolus", "the nucleolus also", "nucleolus also plays", "also plays a", "plays a role", "a role in", "role in p14arf", "in p14arf mediated", "p14arf mediated stabilization", "mediated stabilization of", "stabilization of p53.", "of p53. mutations", "p53. mutations in", "mutations in exon", "in exon 2", "exon 2 of", "2 of the", "cdkn2a gene can", "gene can lead", "can lead to", "lead to missense", "to missense mutations", "missense mutations in", "mutations in p14arf", "in p14arf that", "p14arf that affect", "that affect its", "affect its nucleolar", "its nucleolar localization", "nucleolar localization and", "localization and p53", "and p53 stabilization", "stabilization but", "but the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "has not been", "not been fully", "been fully elucidated", "elucidated zhang", "zhang and xiong", "and xiong 1999", "1999 reviewed", "reviewed by fontana", "by fontana et", "fontana et al.", "et al. 2019", "al. 2019 .", "cell culture p14arf", "p14arf cdkn2a transcript", "transcript 4 cdkn2a", "4 cdkn2a 4", "cdkn2a 4 arf", "arf one", "one of the two", "of the two main", "the two main protein", "two main protein products", "main protein products of", "protein products of the", "products of the cdkn2a", "of the cdkn2a gene", "cdkn2a gene contributes", "gene contributes to", "contributes to oncogene induced", "to oncogene induced senescence", "oncogene induced senescence by", "induced senescence by stabilizing", "senescence by stabilizing tp53", "stabilizing tp53 p53", "tp53 p53 .", "p53 . the function", ". the function of", "the function of p14arf", "function of p14arf in", "of p14arf in p53", "p14arf in p53 stabilization", "in p53 stabilization through", "p53 stabilization through sequestration", "stabilization through sequestration of", "through sequestration of mdm2", "of mdm2 a", "mdm2 a p53", "a p53 ubiquitin ligase", "ubiquitin ligase depends", "ligase depends on", "depends on the nuclear", "on the nuclear localization", "the nuclear localization of", "nuclear localization of p14arf", "localization of p14arf and", "of p14arf and its", "p14arf and its ability", "and its ability to", "its ability to interact", "ability to interact with", "to interact with mdm2.", "interact with mdm2. the", "with mdm2. the nuclear", "mdm2. the nuclear localization", "the nuclear localization signal", "nuclear localization signal and", "localization signal and the", "signal and the mdm2", "and the mdm2 interaction", "the mdm2 interaction domain", "mdm2 interaction domain map", "interaction domain map to", "domain map to the", "map to the first", "to the first 15", "the first 15 amino", "first 15 amino acids", "15 amino acids of", "amino acids of the", "acids of the n", "of the n terminus", "the n terminus of", "n terminus of p14arf.", "terminus of p14arf. this", "of 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frameshift truncation of", "frameshift truncation of p14arf", "of p14arf responsible", "p14arf responsible for", "responsible for a familial", "for a familial melanoma", "a familial melanoma syndrome", "familial melanoma syndrome in", "melanoma syndrome in which", "syndrome in which the", "in which the p16ink4a", "which the p16ink4a product", "the p16ink4a product of", "p16ink4a product of the", "product of the cdkn2a", "the cdkn2a gene is", "cdkn2a gene is unaffected.", "gene is unaffected. this", "is unaffected. this mutation", "unaffected. this mutation is", "this mutation is rare", "mutation is rare and", "is rare and has", "rare and has so", "and has so far", "has so far been", "so far been reported", "far been reported in", "been reported in one", "reported in one family", "in one family only.", "one family only. the", "family only. the mutant", "only. the mutant protein", "mutant protein p14arf", "protein p14arf v22pfs*46", "p14arf v22pfs*46 has the", "v22pfs*46 has the nucleotide", "has the nucleotide localization", "the nucleotide localization signal", "nucleotide localization signal and", "signal and the n", "and the n terminal", "the n terminal mdm2", "n terminal mdm2 interaction", "terminal mdm2 interaction region", "mdm2 interaction region preserved", "region preserved but", "preserved but is", "but is unable to", "is unable to translocate", "unable to translocate from", "to translocate from the", "translocate from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the nucleus", "the nucleus possibly", "nucleus possibly due", "possibly due to aberrant", "due to aberrant conformation", "aberrant conformation rizos", "rizos puig et", "puig et al. 2001", "and also lacks the", "also lacks the c", "lacks the c terminal", "the c terminal mdm2", "c terminal mdm2 interaction", "terminal mdm2 interaction region.", "mdm2 interaction region. relocation", "interaction region. relocation of", "region. relocation of wild", "relocation of wild type", "of wild type p14arf", "wild type p14arf to", "type p14arf to the", "p14arf to the cytosol", "to the cytosol has", "the cytosol has been", "cytosol has been observed", "has been observed in", "been observed in melanoma", "in melanoma rizos", "rizos darmanian et", "darmanian et al. 2001", "al. 2001 and", "2001 and aggressive", "and aggressive thyroid papillary", "aggressive thyroid papillary carcinoma", "papillary carcinoma ferru", "carcinoma ferru et", "ferru et al. 2006", "et al. 2006 .", "al. 2006 . genomic", "2006 . genomic deletion", ". genomic deletion of", "genomic deletion of exon", "deletion of exon 1beta", "exon 1beta with", "1beta with exons", "exons 1alpha 2", "1alpha 2 and", "2 and 3 intact", "3 intact has", "intact has been", "has been reported in", "been reported in about", "reported in about 30%", "in about 30% of", "about 30% of melanoma", "30% of melanoma cases", "of melanoma cases with", "melanoma cases with genomic", "cases with genomic deletions", "with genomic deletions involving", "genomic deletions involving the", "deletions involving the cdkn2a", "involving the cdkn2a locus", "cdkn2a locus freedberg", "locus freedberg et", "freedberg et al. 2008", "et al. 2008 .", "al. 2008 . several", "2008 . several different", ". several different familial", "several different familial melanoma", "different familial melanoma germline", "familial melanoma germline mutations", "melanoma germline mutations map", "germline mutations map to", "mutations map to the", "map to the exon", "to the exon 1beta", "the exon 1beta splice", "exon 1beta splice donor", "1beta splice donor site", "donor site harland", "site harland et", "harland et al. 2005", "et al. 2005 .
              the", "al. 2005 .
              the ability", "2005 .
              the ability of", ".
              the ability of p14arf", "ability of p14arf to", "of p14arf to localize", "p14arf to localize to", "to localize to the", "localize to the nucleolus", "to the nucleolus also", "the nucleolus also plays", "nucleolus also plays a", "also plays a role", "plays a role in", "a role in p14arf", "role in p14arf mediated", "in p14arf mediated stabilization", "p14arf mediated stabilization of", "mediated stabilization of p53.", "stabilization of p53. mutations", "of p53. mutations in", "p53. mutations in exon", "mutations in exon 2", "in exon 2 of", "exon 2 of the", "2 of the cdkn2a", "the cdkn2a gene can", "cdkn2a gene can lead", "gene can lead to", "can lead to missense", "lead to missense mutations", "to missense mutations in", "missense mutations in p14arf", "mutations in p14arf that", "in p14arf that affect", "p14arf that affect its", "that affect its nucleolar", "affect its nucleolar localization", "its nucleolar localization and", "nucleolar localization and p53", "localization and p53 stabilization", "p53 stabilization but", "stabilization but the", "but the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been fully", "not been fully elucidated", "fully elucidated zhang", "elucidated zhang and", "zhang and xiong 1999", "xiong 1999 reviewed", "1999 reviewed by", "reviewed by fontana et", "by fontana et al.", "fontana et al. 2019", "et al. 2019 .", "in cell culture p14arf", "culture p14arf cdkn2a", "p14arf cdkn2a transcript 4", "cdkn2a transcript 4 cdkn2a", "transcript 4 cdkn2a 4", "arf one of", "one of the two main", "of the two main protein", "the two main protein products", "two main protein products of", "main protein products of the", "protein products of the cdkn2a", "products of the cdkn2a gene", "the cdkn2a gene contributes", "cdkn2a gene contributes to", "gene contributes to oncogene", "contributes to oncogene induced senescence", "to oncogene induced senescence by", "oncogene induced senescence by stabilizing", "induced senescence by stabilizing tp53", "by stabilizing tp53 p53", "stabilizing tp53 p53 .", "tp53 p53 . the", "p53 . the function of", ". the function of p14arf", "the function of p14arf in", "function of p14arf in p53", "of p14arf in p53 stabilization", "p14arf in p53 stabilization through", "in p53 stabilization through sequestration", "p53 stabilization through sequestration of", "stabilization through sequestration of mdm2", "sequestration of mdm2 a", "of mdm2 a p53", "mdm2 a p53 ubiquitin", "p53 ubiquitin ligase depends", "ubiquitin ligase depends on", "ligase depends on the", "depends on the nuclear localization", "on the nuclear localization of", "the nuclear localization of p14arf", "nuclear localization of p14arf and", "localization of p14arf and its", "of p14arf and its ability", "p14arf and its ability to", "and its ability to interact", "its ability to interact with", "ability to interact with mdm2.", "to interact with mdm2. the", "interact with mdm2. the nuclear", "with mdm2. the nuclear localization", "mdm2. the nuclear localization signal", "the nuclear localization signal and", "nuclear localization signal and the", "localization signal and the mdm2", "signal and the mdm2 interaction", "and the mdm2 interaction domain", "the mdm2 interaction domain map", "mdm2 interaction domain map to", "interaction domain map to the", "domain map to the first", "map to the first 15", "to the first 15 amino", "the first 15 amino acids", "first 15 amino acids of", "15 amino acids of the", "amino acids of the n", "acids of the n terminus", "of the n terminus of", "the n terminus of p14arf.", "n terminus of p14arf. this", "terminus of p14arf. this region", "of p14arf. this region is", "p14arf. this region is encoded", "this region is encoded by", "region is encoded by the", "is encoded by the p14arf", "encoded by the p14arf specific", "by the p14arf specific exon", "the p14arf specific exon 1beta", "p14arf specific exon 1beta of", "specific exon 1beta of cdkn2a.", "exon 1beta of cdkn2a. an", "1beta of cdkn2a. an independent", "of cdkn2a. an independent mdm2", "cdkn2a. an independent mdm2 binding", "an independent mdm2 binding domain", "independent mdm2 binding domain localized", "mdm2 binding domain localized to", "binding domain localized to the", "domain localized to the c", "localized to the c terminus", "to the c terminus of", "the c terminus of p14arf", "terminus of p14arf lohrum", "of p14arf lohrum et", "p14arf lohrum et al.", "lohrum et al. 2000 .", "et al. 2000 . insertion", "al. 2000 . insertion of", "2000 . insertion of 16", ". insertion of 16 nucleotides", "insertion of 16 nucleotides in", "of 16 nucleotides in exon", "16 nucleotides in exon 1beta", "nucleotides in exon 1beta results", "in exon 1beta results in", "exon 1beta results in a", "1beta results in a frameshift", "results in a frameshift truncation", "in a frameshift truncation of", "a frameshift truncation of p14arf", "truncation of p14arf responsible", "of p14arf responsible for", "p14arf responsible for a", "responsible for a familial melanoma", "for a familial melanoma syndrome", "a familial melanoma syndrome in", "familial melanoma syndrome in which", "melanoma syndrome in which the", "syndrome in which the p16ink4a", "in which the p16ink4a product", "which the p16ink4a product of", "the p16ink4a product of the", "p16ink4a product of the cdkn2a", "product of the cdkn2a gene", "of the cdkn2a gene is", "the cdkn2a gene is unaffected.", "cdkn2a gene is unaffected. this", "gene is unaffected. this mutation", "is unaffected. this mutation is", "unaffected. this mutation is rare", "this mutation is rare and", "mutation is rare and has", "is rare and has so", "rare and has so far", "and has so far been", "has so far been reported", "so far been reported in", "far been reported in one", "been reported in one family", "reported in one family only.", "in one family only. the", "one family only. the mutant", "family only. the mutant protein", "the mutant protein p14arf", "mutant protein p14arf v22pfs*46", "protein p14arf v22pfs*46 has", "p14arf v22pfs*46 has the nucleotide", "v22pfs*46 has the nucleotide localization", "has the nucleotide localization signal", "the nucleotide localization signal and", "nucleotide localization signal and the", "localization signal and the n", "signal and the n terminal", "and the n terminal mdm2", "the n terminal mdm2 interaction", "n terminal mdm2 interaction region", "terminal mdm2 interaction region preserved", "interaction region preserved but", "region preserved but is", "preserved but is unable", "but is unable to translocate", "is unable to translocate from", "unable to translocate from the", "to translocate from the cytosol", "translocate from the cytosol to", "from the cytosol to the", "the cytosol to the nucleus", "to the nucleus possibly", "the nucleus possibly due", "nucleus possibly due to", "possibly due to aberrant conformation", "to aberrant conformation rizos", "conformation rizos puig", "rizos puig et al.", "2001 and also", "and also lacks the c", "also lacks the c terminal", "lacks the c terminal mdm2", "the c terminal mdm2 interaction", "c terminal mdm2 interaction region.", "terminal mdm2 interaction region. relocation", "mdm2 interaction region. relocation of", "interaction region. relocation of wild", "region. relocation of wild type", "relocation of wild type p14arf", "of wild type p14arf to", "wild type p14arf to the", "type p14arf to the cytosol", "p14arf to the cytosol has", "to the cytosol has been", "the cytosol has been observed", "cytosol has been observed in", "has been observed in melanoma", "observed in melanoma rizos", "melanoma rizos darmanian", "rizos darmanian et al.", "et al. 2001 and", "al. 2001 and aggressive", "2001 and aggressive thyroid", "and aggressive thyroid papillary carcinoma", "thyroid papillary carcinoma ferru", "papillary carcinoma ferru et", "carcinoma ferru et al.", "ferru et al. 2006 .", "et al. 2006 . genomic", "al. 2006 . genomic deletion", "2006 . genomic deletion of", ". genomic deletion of exon", "genomic deletion of exon 1beta", "of exon 1beta with", "exon 1beta with exons", "1beta with exons 1alpha", "with exons 1alpha 2", "exons 1alpha 2 and", "1alpha 2 and 3", "and 3 intact has", "3 intact has been", "intact has been reported", "has been reported in about", "been reported in about 30%", "reported in about 30% of", "in about 30% of melanoma", "about 30% of melanoma cases", "30% of melanoma cases with", "of melanoma cases with genomic", "melanoma cases with genomic deletions", "cases with genomic deletions involving", "with genomic deletions involving the", "genomic deletions involving the cdkn2a", "deletions involving the cdkn2a locus", "the cdkn2a locus freedberg", "cdkn2a locus freedberg et", "locus freedberg et al.", "freedberg et al. 2008 .", "et al. 2008 . several", "al. 2008 . several different", "2008 . several different familial", ". several different familial melanoma", "several different familial melanoma germline", "different familial melanoma germline mutations", "familial melanoma germline mutations map", "melanoma germline mutations map to", "germline mutations map to the", "mutations map to the exon", "map to the exon 1beta", "to the exon 1beta splice", "the exon 1beta splice donor", "exon 1beta splice donor site", "splice donor site harland", "donor site harland et", "site harland et al.", "harland et al. 2005 .
              the", "et al. 2005 .
              the ability", "al. 2005 .
              the ability of", "2005 .
              the ability of p14arf", ".
              the ability of p14arf to", "ability of p14arf to localize", "of p14arf to localize to", "p14arf to localize to the", "to localize to the nucleolus", "localize to the nucleolus also", "to the nucleolus also plays", "the nucleolus also plays a", "nucleolus also plays a role", "also plays a role in", "plays a role in p14arf", "a role in p14arf mediated", "role in p14arf mediated stabilization", "in p14arf mediated stabilization of", "p14arf mediated stabilization of p53.", "mediated stabilization of p53. mutations", "stabilization of p53. mutations in", "of p53. mutations in exon", "p53. mutations in exon 2", "mutations in exon 2 of", "in exon 2 of the", "exon 2 of the cdkn2a", "2 of the cdkn2a gene", "of the cdkn2a gene can", "the cdkn2a gene can lead", "cdkn2a gene can lead to", "gene can lead to missense", "can lead to missense mutations", "lead to missense mutations in", "to missense mutations in p14arf", "missense mutations in p14arf that", "mutations in p14arf that affect", "in p14arf that affect its", "p14arf that affect its nucleolar", "that affect its nucleolar localization", "affect its nucleolar localization and", "its nucleolar localization and p53", "nucleolar localization and p53 stabilization", "and p53 stabilization but", "p53 stabilization but the", "stabilization but the exact", "but the exact mechanism has", "the exact mechanism has not", "exact mechanism has not been", "mechanism has not been fully", "has not been fully elucidated", "been fully elucidated zhang", "fully elucidated zhang and", "elucidated zhang and xiong", "and xiong 1999 reviewed", "xiong 1999 reviewed by", "1999 reviewed by fontana", "reviewed by fontana et al.", "by fontana et al. 2019", "fontana et al. 2019 ." ] }, { "record_id": "GLY_000594_1_1837", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9646304", "r hsa", "hsa 9646304", "r hsa 9646304" ] }, { "record_id": "GLY_000594_1_1837", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "evasion of", "of oxidative", "oxidative stress", "stress induced", "induced senescence", "senescence due", "due to", "to p14arf", "p14arf defects", "evasion of oxidative", "of oxidative stress", "oxidative stress induced", "stress induced senescence", "induced senescence due", "senescence due to", "due to p14arf", "to p14arf defects", "evasion of oxidative stress", "of oxidative stress induced", "oxidative stress induced senescence", "stress induced senescence due", "induced senescence due to", "senescence due to p14arf", "due to p14arf defects", "evasion of oxidative stress induced", "of oxidative stress induced senescence", "oxidative stress induced senescence due", "stress induced senescence due to", "induced senescence due to p14arf", "senescence due to p14arf defects", "one of", "of the", "the two", "two main", "main protein", "protein products", "products of", "the cdkn2a", "cdkn2a gene", "cdkn2a transcript", "transcript 4", "cdkn2a 4", "contributes to", "to oxidative", "induced cellular", "cellular senescence", "senescence by", "by stabilizing", "stabilizing tp53", "p53 .", ". the", "the function", "function of", "of p14arf", "p14arf in", "in p53", "p53 stabilization", "stabilization through", "through sequestration", "sequestration of", "of mdm2", "a p53", "p53 ubiquitin", "ubiquitin ligase", "depends on", "on the", "the nuclear", "nuclear localization", "localization of", "p14arf and", "and its", "its ability", "ability to", "to interact", "interact with", "with mdm2.", "mdm2. the", "localization signal", "signal and", "and the", "the mdm2", "mdm2 interaction", "interaction domain", "domain map", "map to", "to the", "the first", "first 15", "15 amino", "amino acids", "acids of", "the n", "n terminus", "terminus of", "of p14arf.", "p14arf. this", "this region", "region is", "is encoded", "encoded by", "by the", "the p14arf", "p14arf specific", "specific exon", "exon 1beta", "1beta of", "of cdkn2a.", "cdkn2a. an", "an independent", "independent mdm2", "mdm2 binding", "binding domain", "domain is", "is localized", "localized at", "at the", "the c", "c terminus", "lohrum et", "et al.", "al. 2000", "2000 .", ". insertion", "insertion of", "of 16", "16 nucleotides", "nucleotides in", "in exon", "1beta results", "results in", "in a", "a frameshift", "frameshift truncation", "truncation of", "responsible for", "for a", "a familial", "familial melanoma", "melanoma syndrome", "syndrome in", "in which", "which the", "the p16ink4a", "p16ink4a product", "product of", "gene is", "is unaffected.", "unaffected. this", "this mutation", "mutation is", "is rare", "rare and", "and has", "has so", "so far", "far been", "been reported", "reported in", "in one", "one family", "family only.", "only. the", "the mutant", "mutant protein", "p14arf v22pfs*46", "v22pfs*46 has", "has the", "the nucleotide", "nucleotide localization", "n terminal", "terminal mdm2", "interaction region", "region preserved", "but is", "is unable", "unable to", "to translocate", "translocate from", "from the", "the cytosol", "cytosol to", "the nucleus", "possibly due", "to aberrant", "aberrant conformation", "puig et", "al. 2001", "and also", "also lacks", "lacks the", "c terminal", "interaction region.", "region. relocation", "relocation of", "of wild", "wild type", "type p14arf", "p14arf to", "cytosol has", "has been", "been observed", "observed in", "in melanoma", "darmanian et", "and aggressive", "aggressive thyroid", "thyroid papillary", "papillary carcinoma", "ferru et", "al. 2006", "2006 .", ". genomic", "genomic deletion", "deletion of", "of exon", "with exons", "exons 1alpha", "2 and", "and 3", "3 intact", "in about", "about 30%", "30% of", "of melanoma", "melanoma cases", "cases with", "with genomic", "genomic deletions", "deletions involving", "involving the", "cdkn2a locus", "freedberg et", "al. 2008", "2008 .", ". several", "several different", "different familial", "melanoma germline", "germline mutations", "mutations map", "the exon", "1beta splice", "splice donor", "donor site", "harland et", "al. 2005", "2005 .
              the", ".
              the ability", "ability of", "to localize", "localize to", "the nucleolus", "nucleolus also", "also plays", "plays a", "a role", "role in", "in p14arf", "p14arf mediated", "mediated stabilization", "stabilization of", "of p53.", "p53. mutations", "mutations in", "exon 2", "2 of", "gene can", "can lead", "lead to", "to missense", "missense mutations", "p14arf that", "that affect", "affect its", "its nucleolar", "nucleolar localization", "localization and", "and p53", "but the", "the exact", "exact mechanism", "mechanism has", "has not", "not been", "been fully", "fully elucidated", "zhang and", "and xiong", "xiong 1999", "reviewed by", "by fontana", "fontana et", "al. 2019", "2019 .", "one of the", "of the two", "the two main", "two main protein", "main protein products", "protein products of", "products of the", "of the cdkn2a", "the cdkn2a gene", "gene p14arf", "p14arf cdkn2a", "cdkn2a transcript 4", "4 cdkn2a", "4 arf", "contributes to oxidative", "to oxidative stress", "stress induced cellular", "induced cellular senescence", "cellular senescence by", "senescence by stabilizing", "by stabilizing tp53", "tp53 p53", "p53 . the", ". the function", "the function of", "function of p14arf", "of p14arf in", "p14arf in p53", "in p53 stabilization", "p53 stabilization through", "stabilization through sequestration", "through sequestration of", "sequestration of mdm2", "mdm2 a", "a p53 ubiquitin", "p53 ubiquitin ligase", "ligase depends", "depends on the", "on the nuclear", "the nuclear localization", "nuclear localization of", "localization of p14arf", "of p14arf and", "p14arf and its", "and its ability", "its ability to", "ability to interact", "to interact with", "interact with mdm2.", "with mdm2. the", "mdm2. the nuclear", "nuclear localization signal", "localization signal and", "signal and the", "and the mdm2", "the mdm2 interaction", "mdm2 interaction domain", "interaction domain map", "domain map to", "map to the", "to the first", "the first 15", "first 15 amino", "15 amino acids", "amino acids of", "acids of the", "of the n", "the n terminus", "n terminus of", "terminus of p14arf.", "of p14arf. this", "p14arf. this region", "this region is", "region is encoded", "is encoded by", "encoded by the", "by the p14arf", "the p14arf specific", "p14arf specific exon", "specific exon 1beta", "exon 1beta of", "1beta of cdkn2a.", "of cdkn2a. an", "cdkn2a. an independent", "an independent mdm2", "independent mdm2 binding", "mdm2 binding domain", "binding domain is", "domain is localized", "is localized at", "localized at the", "at the c", "the c terminus", "c terminus of", "terminus of p14arf", "p14arf lohrum", "lohrum et al.", "et al. 2000", "al. 2000 .", "2000 . insertion", ". insertion of", "insertion of 16", "of 16 nucleotides", "16 nucleotides in", "nucleotides in exon", "in exon 1beta", "exon 1beta results", "1beta results in", "results in a", "in a frameshift", "a frameshift truncation", "frameshift truncation of", "truncation of p14arf", "p14arf responsible", "responsible for a", "for a familial", "a familial melanoma", "familial melanoma syndrome", "melanoma syndrome in", "syndrome in which", "in which the", "which the p16ink4a", "the p16ink4a product", "p16ink4a product of", "product of the", "cdkn2a gene is", "gene is unaffected.", "is unaffected. this", "unaffected. this mutation", "this mutation is", "mutation is rare", "is rare and", "rare and has", "and has so", "has so far", "so far been", "far been reported", "been reported in", "reported in one", "in one family", "one family only.", "family only. the", "only. the mutant", "the mutant protein", "protein p14arf", "p14arf v22pfs*46 has", "v22pfs*46 has the", "has the nucleotide", "the nucleotide localization", "nucleotide localization signal", "and the n", "the n terminal", "n terminal mdm2", "terminal mdm2 interaction", "mdm2 interaction region", "interaction region preserved", "preserved but", "but is unable", "is unable to", "unable to translocate", "to translocate from", "translocate from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the nucleus", "nucleus possibly", "possibly due to", "due to aberrant", "to aberrant conformation", "conformation rizos", "rizos puig", "puig et al.", "et al. 2001", "and also lacks", "also lacks the", "lacks the c", "the c terminal", "c terminal mdm2", "mdm2 interaction region.", "interaction region. relocation", "region. relocation of", "relocation of wild", "of wild type", "wild type p14arf", "type p14arf to", "p14arf to the", "to the cytosol", "the cytosol has", "cytosol has been", "has been observed", "been observed in", "observed in melanoma", "melanoma rizos", "rizos darmanian", "darmanian et al.", "2001 and", "and aggressive thyroid", "aggressive thyroid papillary", "thyroid papillary carcinoma", "carcinoma ferru", "ferru et al.", "et al. 2006", "al. 2006 .", "2006 . genomic", ". genomic deletion", "genomic deletion of", "deletion of exon", "of exon 1beta", "1beta with", "with exons 1alpha", "1alpha 2", "2 and 3", "and 3 intact", "intact has", "has been reported", "reported in about", "in about 30%", "about 30% of", "30% of melanoma", "of melanoma cases", "melanoma cases with", "cases with genomic", "with genomic deletions", "genomic deletions involving", "deletions involving the", "involving the cdkn2a", "the cdkn2a locus", "locus freedberg", "freedberg et al.", "et al. 2008", "al. 2008 .", "2008 . several", ". several different", "several different familial", "different familial melanoma", "familial melanoma germline", "melanoma germline mutations", "germline mutations map", "mutations map to", "to the exon", "the exon 1beta", "exon 1beta splice", "1beta splice donor", "splice donor site", "site harland", "harland et al.", "et al. 2005", "al. 2005 .
              the", "2005 .
              the ability", ".
              the ability of", "ability of p14arf", "of p14arf to", "p14arf to localize", "to localize to", "localize to the", "to the nucleolus", "the nucleolus also", "nucleolus also plays", "also plays a", "plays a role", "a role in", "role in p14arf", "in p14arf mediated", "p14arf mediated stabilization", "mediated stabilization of", "stabilization of p53.", "of p53. mutations", "p53. mutations in", "mutations in exon", "in exon 2", "exon 2 of", "2 of the", "cdkn2a gene can", "gene can lead", "can lead to", "lead to missense", "to missense mutations", "missense mutations in", "mutations in p14arf", "in p14arf that", "p14arf that affect", "that affect its", "affect its nucleolar", "its nucleolar localization", "nucleolar localization and", "localization and p53", "and p53 stabilization", "stabilization but", "but the exact", "the exact mechanism", "exact mechanism has", "mechanism has not", "has not been", "not been fully", "been fully elucidated", "elucidated zhang", "zhang and xiong", "and xiong 1999", "1999 reviewed", "reviewed by fontana", "by fontana et", "fontana et al.", "et al. 2019", "al. 2019 .", "one of the two", "of the two main", "the two main protein", "two main protein products", "main protein products of", "protein products of the", "products of the cdkn2a", "of the cdkn2a gene", "cdkn2a gene p14arf", "p14arf cdkn2a transcript", "transcript 4 cdkn2a", "4 cdkn2a 4", "cdkn2a 4 arf", "arf contributes", "contributes to oxidative stress", "to oxidative stress induced", "oxidative stress induced cellular", "stress induced cellular senescence", "induced cellular senescence by", "cellular senescence by stabilizing", "senescence by stabilizing tp53", "stabilizing tp53 p53", "tp53 p53 .", "p53 . the function", ". the function of", "the function of p14arf", "function of p14arf in", "of p14arf in p53", "p14arf in p53 stabilization", "in p53 stabilization through", "p53 stabilization through sequestration", "stabilization through sequestration of", "through sequestration of mdm2", "of mdm2 a", "mdm2 a p53", "a p53 ubiquitin ligase", "ubiquitin ligase depends", "ligase depends on", "depends on the nuclear", "on the nuclear localization", "the nuclear localization of", "nuclear localization of p14arf", "localization of p14arf and", "of p14arf and its", "p14arf and its ability", "and its ability to", "its ability to interact", "ability to interact with", "to interact with mdm2.", "interact with mdm2. the", "with mdm2. the nuclear", "mdm2. the nuclear localization", "the nuclear localization signal", "nuclear localization signal and", "localization signal and the", "signal and the mdm2", "and the mdm2 interaction", "the mdm2 interaction domain", "mdm2 interaction domain map", "interaction domain map to", "domain map to the", "map to the first", "to the first 15", "the first 15 amino", "first 15 amino acids", "15 amino acids of", "amino acids of the", "acids of the n", "of the n terminus", "the n terminus of", "n terminus of p14arf.", "terminus of p14arf. this", "of p14arf. this region", "p14arf. this region is", "this region is encoded", "region is encoded by", "is encoded by the", "encoded by the p14arf", "by the p14arf specific", "the p14arf specific exon", "p14arf specific exon 1beta", "specific exon 1beta of", "exon 1beta of cdkn2a.", "1beta of cdkn2a. an", "of cdkn2a. an independent", "cdkn2a. an independent mdm2", "an independent mdm2 binding", "independent mdm2 binding domain", "mdm2 binding domain is", "binding domain is localized", "domain is localized at", "is localized at the", "localized at the c", "at the c terminus", "the c terminus of", "c terminus of p14arf", "of p14arf lohrum", "p14arf lohrum et", "lohrum et al. 2000", "et al. 2000 .", "al. 2000 . insertion", "2000 . insertion of", ". insertion of 16", "insertion of 16 nucleotides", "of 16 nucleotides in", "16 nucleotides in exon", "nucleotides in exon 1beta", "in exon 1beta results", "exon 1beta results in", "1beta results in a", "results in a frameshift", "in a frameshift truncation", "a frameshift truncation of", "frameshift truncation of p14arf", "of p14arf responsible", "p14arf responsible for", "responsible for a familial", "for a familial melanoma", "a familial melanoma syndrome", "familial melanoma syndrome in", "melanoma syndrome in which", "syndrome in which the", "in which the p16ink4a", "which the p16ink4a product", "the p16ink4a product of", "p16ink4a product of the", "product of the cdkn2a", "the cdkn2a gene is", "cdkn2a gene is unaffected.", "gene is unaffected. this", "is unaffected. this mutation", "unaffected. this mutation is", "this mutation is rare", "mutation is rare and", "is rare and has", "rare and has so", "and has so far", "has so far been", "so far been reported", "far been reported in", "been reported in one", "reported in one family", "in one family only.", "one family only. the", "family only. the mutant", "only. the mutant protein", "mutant protein p14arf", "protein p14arf v22pfs*46", "p14arf v22pfs*46 has the", "v22pfs*46 has the nucleotide", "has the nucleotide localization", "the nucleotide localization signal", "nucleotide localization signal and", "signal and the n", "and the n terminal", "the n terminal mdm2", "n terminal mdm2 interaction", "terminal mdm2 interaction region", "mdm2 interaction region preserved", "region preserved but", "preserved but is", "but is unable to", "is unable to translocate", "unable to translocate from", "to translocate from the", "translocate from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the nucleus", "the nucleus possibly", "nucleus possibly due", "possibly due to aberrant", "due to aberrant conformation", "aberrant conformation rizos", "rizos puig et", "puig et al. 2001", "and also lacks the", "also lacks the c", "lacks the c terminal", "the c terminal mdm2", "c terminal mdm2 interaction", "terminal mdm2 interaction region.", "mdm2 interaction region. relocation", "interaction region. relocation of", "region. relocation of wild", "relocation of wild type", "of wild type p14arf", "wild type p14arf to", "type p14arf to the", "p14arf to the cytosol", "to the cytosol has", "the cytosol has been", "cytosol has been observed", "has been observed in", "been observed in melanoma", "in melanoma rizos", "rizos darmanian et", "darmanian et al. 2001", "al. 2001 and", "2001 and aggressive", "and aggressive thyroid papillary", "aggressive thyroid papillary carcinoma", "papillary carcinoma ferru", "carcinoma ferru et", "ferru et al. 2006", "et al. 2006 .", "al. 2006 . genomic", "2006 . genomic deletion", ". genomic deletion of", "genomic deletion of exon", "deletion of exon 1beta", "exon 1beta with", "1beta with exons", "exons 1alpha 2", "1alpha 2 and", "2 and 3 intact", "3 intact has", "intact has been", "has been reported in", "been reported in about", "reported in about 30%", "in about 30% of", "about 30% of melanoma", "30% of melanoma cases", "of melanoma cases with", "melanoma cases with genomic", "cases with genomic deletions", "with genomic deletions involving", "genomic deletions involving the", "deletions involving the cdkn2a", "involving the cdkn2a locus", "cdkn2a locus freedberg", "locus freedberg et", "freedberg et al. 2008", "et al. 2008 .", "al. 2008 . several", "2008 . several different", ". several different familial", "several different familial melanoma", "different familial melanoma germline", "familial melanoma germline mutations", "melanoma germline mutations map", "germline mutations map to", "mutations map to the", "map to the exon", "to the exon 1beta", "the exon 1beta splice", "exon 1beta splice donor", "1beta splice donor site", "donor site harland", "site harland et", "harland et al. 2005", "et al. 2005 .
              the", "al. 2005 .
              the ability", "2005 .
              the ability of", ".
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"localization and p53 stabilization", "p53 stabilization but", "stabilization but the", "but the exact mechanism", "the exact mechanism has", "exact mechanism has not", "mechanism has not been", "has not been fully", "not been fully elucidated", "fully elucidated zhang", "elucidated zhang and", "zhang and xiong 1999", "xiong 1999 reviewed", "1999 reviewed by", "reviewed by fontana et", "by fontana et al.", "fontana et al. 2019", "et al. 2019 .", "one of the two main", "of the two main protein", "the two main protein products", "two main protein products of", "main protein products of the", "protein products of the cdkn2a", "products of the cdkn2a gene", "the cdkn2a gene p14arf", "gene p14arf cdkn2a", "p14arf cdkn2a transcript 4", "cdkn2a transcript 4 cdkn2a", "transcript 4 cdkn2a 4", "arf contributes to", "contributes to oxidative stress induced", "to oxidative stress induced cellular", "oxidative stress induced cellular senescence", "stress induced cellular senescence by", "induced cellular senescence by stabilizing", "cellular senescence by stabilizing tp53", "by stabilizing tp53 p53", "stabilizing tp53 p53 .", "tp53 p53 . the", "p53 . the function of", ". the function of p14arf", "the function of p14arf in", "function of p14arf in p53", "of p14arf in p53 stabilization", "p14arf in p53 stabilization through", "in p53 stabilization through sequestration", "p53 stabilization through sequestration of", "stabilization through sequestration of mdm2", "sequestration of mdm2 a", "of mdm2 a p53", "mdm2 a p53 ubiquitin", "p53 ubiquitin ligase depends", "ubiquitin ligase depends on", "ligase depends on the", "depends on the nuclear localization", "on the nuclear localization of", "the nuclear localization of p14arf", "nuclear localization of p14arf and", "localization of p14arf and its", "of p14arf and its ability", "p14arf and its ability to", "and its ability to interact", "its ability to interact with", "ability to interact with mdm2.", "to interact with mdm2. the", "interact with mdm2. the nuclear", "with mdm2. the nuclear localization", "mdm2. the nuclear localization signal", "the nuclear localization signal and", "nuclear localization signal and the", "localization signal and the mdm2", "signal and the mdm2 interaction", "and the mdm2 interaction domain", "the mdm2 interaction domain map", "mdm2 interaction domain map to", "interaction domain map to the", "domain map to the first", "map to the first 15", "to the first 15 amino", "the first 15 amino acids", "first 15 amino acids of", "15 amino acids of the", "amino acids of the n", "acids of the n terminus", "of the n terminus of", "the n terminus of p14arf.", "n terminus of p14arf. this", "terminus of p14arf. this region", "of p14arf. this region is", "p14arf. this region is encoded", "this region is encoded by", "region is encoded by the", "is encoded by the p14arf", "encoded by the p14arf specific", "by the p14arf specific exon", "the p14arf specific exon 1beta", "p14arf specific exon 1beta of", "specific exon 1beta of cdkn2a.", "exon 1beta of cdkn2a. an", "1beta of cdkn2a. an independent", "of cdkn2a. an independent mdm2", "cdkn2a. an independent mdm2 binding", "an independent mdm2 binding domain", "independent mdm2 binding domain is", "mdm2 binding domain is localized", "binding domain is localized at", "domain is localized at the", "is localized at the c", "localized at the c terminus", "at the c terminus of", "the c terminus of p14arf", "terminus of p14arf lohrum", "of p14arf lohrum et", "p14arf lohrum et al.", "lohrum et al. 2000 .", "et al. 2000 . insertion", "al. 2000 . insertion of", "2000 . insertion of 16", ". insertion of 16 nucleotides", "insertion of 16 nucleotides in", "of 16 nucleotides in exon", "16 nucleotides in exon 1beta", "nucleotides in exon 1beta results", "in exon 1beta results in", "exon 1beta results in a", "1beta results in a frameshift", "results in a frameshift truncation", "in a frameshift truncation of", "a frameshift truncation of p14arf", "truncation of p14arf responsible", "of p14arf responsible for", "p14arf responsible for a", "responsible for a familial melanoma", "for a familial melanoma syndrome", "a familial melanoma syndrome in", "familial melanoma syndrome in which", "melanoma syndrome in which the", "syndrome in which the p16ink4a", "in which the p16ink4a product", "which the p16ink4a product of", "the p16ink4a product of the", "p16ink4a product of the cdkn2a", "product of the cdkn2a gene", "of the cdkn2a gene is", "the cdkn2a gene is unaffected.", "cdkn2a gene is unaffected. this", "gene is unaffected. this mutation", "is unaffected. this mutation is", "unaffected. this mutation is rare", "this mutation is rare and", "mutation is rare and has", "is rare and has so", "rare and has so far", "and has so far been", "has so far been reported", "so far been reported in", "far been reported in one", "been reported in one family", "reported in one family only.", "in one family only. the", "one family only. the mutant", "family only. the mutant protein", "the mutant protein p14arf", "mutant protein p14arf v22pfs*46", "protein p14arf v22pfs*46 has", "p14arf v22pfs*46 has the nucleotide", "v22pfs*46 has the nucleotide localization", "has the nucleotide localization signal", "the nucleotide localization signal and", "nucleotide localization signal and the", "localization signal and the n", "signal and the n terminal", "and the n terminal mdm2", "the n terminal mdm2 interaction", "n terminal mdm2 interaction region", "terminal mdm2 interaction region preserved", "interaction region preserved but", "region preserved but is", "preserved but is unable", "but is unable to translocate", "is unable to translocate from", "unable to translocate from the", "to translocate from the cytosol", "translocate from the cytosol to", "from the cytosol to the", "the cytosol to the nucleus", "to the nucleus possibly", "the nucleus possibly due", "nucleus possibly due to", "possibly due to aberrant conformation", "to aberrant conformation rizos", "conformation rizos puig", "rizos puig et al.", "2001 and also", "and also lacks the c", "also lacks the c terminal", "lacks the c terminal mdm2", "the c terminal mdm2 interaction", "c terminal mdm2 interaction region.", "terminal mdm2 interaction region. relocation", "mdm2 interaction region. relocation of", "interaction region. relocation of wild", "region. relocation of wild type", "relocation of wild type p14arf", "of wild type p14arf to", "wild type p14arf to the", "type p14arf to the cytosol", "p14arf to the cytosol has", "to the cytosol has been", "the cytosol has been observed", "cytosol has been observed in", "has been observed in melanoma", "observed in melanoma rizos", "melanoma rizos darmanian", "rizos darmanian et al.", "et al. 2001 and", "al. 2001 and aggressive", "2001 and aggressive thyroid", "and aggressive thyroid papillary carcinoma", "thyroid papillary carcinoma ferru", "papillary carcinoma ferru et", "carcinoma ferru et al.", "ferru et al. 2006 .", "et al. 2006 . genomic", "al. 2006 . genomic deletion", "2006 . genomic deletion of", ". genomic deletion of exon", "genomic deletion of exon 1beta", "of exon 1beta with", "exon 1beta with exons", "1beta with exons 1alpha", "with exons 1alpha 2", "exons 1alpha 2 and", "1alpha 2 and 3", "and 3 intact has", "3 intact has been", "intact has been reported", "has been reported in about", "been reported in about 30%", "reported in about 30% of", "in about 30% of melanoma", "about 30% of melanoma cases", "30% of melanoma cases with", "of melanoma cases with genomic", "melanoma cases with genomic deletions", "cases with genomic deletions involving", "with genomic deletions involving the", "genomic deletions involving the cdkn2a", "deletions involving the cdkn2a locus", "the cdkn2a locus freedberg", "cdkn2a locus freedberg et", "locus freedberg et al.", "freedberg et al. 2008 .", "et al. 2008 . several", "al. 2008 . several different", "2008 . several different familial", ". several different familial melanoma", "several different familial melanoma germline", "different familial melanoma germline mutations", "familial melanoma germline mutations map", "melanoma germline mutations map to", "germline mutations map to the", "mutations map to the exon", "map to the exon 1beta", "to the exon 1beta splice", "the exon 1beta splice donor", "exon 1beta splice donor site", "splice donor site harland", "donor site harland et", "site harland et al.", "harland et al. 2005 .
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"proteins like the ace2 receptor." ] }, { "record_id": "GLY_000594_1_1840", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9694686", "r hsa", "hsa 9694686", "r hsa 9694686" ] }, { "record_id": "GLY_000594_1_1840", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "replication of", "of the", "the sars", "sars cov", "cov 2", "2 genome", "replication of the", "of the sars", "the sars cov", "sars cov 2", "cov 2 genome", "replication of the sars", "of the sars cov", "the sars cov 2", "sars cov 2 genome", "replication of the sars cov", "of the sars cov 2", "the sars cov 2 genome", "this covid", "covid 19", "19 pathway", "pathway has", "has been", "been created", "created by", "by a", "a combination", "combination of", "of computational", "computational inference", "inference from", "from sars", "cov 1", "1 data", "https://reactome.org/documentation/inferred events", "and manual", "manual curation", "as 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              the plus strand rna", "plus strand rna genome", "strand rna genome of", "rna genome of the", "genome of the human", "of the human sars", "the human sars coronavirus", "human sars coronavirus 1", "coronavirus 1 sars", "1 sars cov", "cov 1 is", "1 is replicated", "is replicated by the", "replicated by the viral", "by the viral replication", "the viral replication transcription", "viral replication transcription complex", "rtc composed of", "composed of nonstructural proteins", "of nonstructural proteins nsp3", "nonstructural proteins nsp3 nsp16", "nsp3 nsp16 encoded", "nsp16 encoded by", "encoded by open reading", "by open reading frames", "open reading frames orf1a", "reading frames orf1a and", "frames orf1a and orf1b.", "orf1a and orf1b. two", "and orf1b. two rtc", "orf1b. two rtc proteins", "rtc proteins nsp8", "proteins nsp8 and", "and nsp12 possess", "nsp12 possess 5'", "possess 5' 3' rna", "5' 3' rna dependent", "3' rna dependent rna", "rna dependent rna polymerase", "dependent rna polymerase activity.", "rna polymerase activity. nsp12", "polymerase activity. nsp12 is", "activity. nsp12 is the", "nsp12 is the main", "is the main rna", "the main rna polymerase", "rna polymerase while", "polymerase while nsp8", "while nsp8 is thought", "nsp8 is thought to", "is thought to act", "thought to act as", "to act as an", "act as an rna", "as an rna primase.", "an rna primase. nsp14", "rna primase. nsp14 acts", "primase. nsp14 acts as", "nsp14 acts as a", "acts as a 3'", "as a 3' 5'", "a 3' 5' exonuclease", "5' exonuclease increasing", "exonuclease increasing the", "increasing the fidelity of", "the fidelity of the", "fidelity of the rtc.", "of the rtc. nsp14", "the rtc. nsp14 also", "rtc. nsp14 also has", "nsp14 also has the", "also has the rna", "has the rna capping", "the rna capping activity", "rna capping activity and", "activity and in", "and in concert", "in concert with nsp16", "with nsp16 it", "nsp16 it caps", "it caps viral plus", "caps viral plus strand", "viral plus strand and", "plus strand and minus", "strand and minus strand", "and minus strand genomic", "minus strand genomic and", "strand genomic and subgenomic", "genomic and subgenomic rnas", "subgenomic rnas which", "rnas which confers", "which confers stability to", "confers stability to viral", "stability to viral rnas", "to viral rnas by", "viral rnas by enabling", "rnas by enabling them", "by enabling them to", "enabling them to escape", "them to escape interferon", "to escape interferon mediated", "escape interferon mediated innate", "interferon mediated innate immune", "mediated innate immune responses", "innate immune responses of", "immune responses of the", "responses of the host.", "of the host. nsp13", "the host. nsp13 is", "host. nsp13 is an", "nsp13 is an rna", "is an rna helicase", "an rna helicase which", "rna helicase which is", "helicase which is thought", "which is thought to", "is thought to melt", "thought to melt secondary", "to melt secondary structures", "melt secondary structures in", "secondary structures in the", "structures in the genomic", "in the genomic rna", "the genomic rna during", "genomic rna during replication", "rna during replication and", "during replication and transcription.", "replication and transcription. the", "and transcription. the plus", "transcription. the plus strand", "the plus strand genomic", "plus strand genomic rna", "strand genomic rna is", "genomic rna is first", "rna is first used", "is first used to", "first used to synthesize", "used to synthesize the", "to synthesize the minus", "synthesize the minus strand", "the minus strand genomic", "minus strand genomic rna", "strand genomic rna complement", "rna complement which", "complement which is", "which is subsequently used", "is subsequently used as", "subsequently used as a", "used as a template", "as a template for", "a template for synthesis", "template for synthesis of", "for synthesis of plus", "synthesis of plus strand", "of plus strand viral", "plus strand viral rna", "strand viral rna genomes", "viral rna genomes that", "rna genomes that are", "genomes that are packaged", "that are packaged into", "are packaged into mature", "packaged into mature virions.", "into mature virions. for", "mature virions. for review", "for review please", "review please refer", "please refer to yang", "refer to yang and", "to yang and leibowitz", "yang and leibowitz 2015", "leibowitz 2015 snijder", "2015 snijder et", "snijder et al. 2016", "al. 2016 fung", "2016 fung and", "fung and liu 2019.", "this covid 19 pathway has", "covid 19 pathway has been", "19 pathway has been created", "pathway has been created by", "has been created by a", "been created by a combination", "created by a combination of", "by a combination of computational", "a combination of computational inference", "combination of computational inference from", "of computational inference from sars", "computational inference from sars cov", "inference from sars cov 1", "from sars cov 1 data", "cov 1 data https://reactome.org/documentation/inferred", "1 data https://reactome.org/documentation/inferred events", "https://reactome.org/documentation/inferred events and manual", "events and manual curation", "and manual curation as", "manual curation as described", "curation as described in", "as described in the summation", "described in the summation for", "in the summation for the", "the summation for the overall", "summation for the overall sars", "for the overall sars cov", "the overall sars cov 2", "overall sars cov 2 infection", "sars cov 2 infection pathway.", "cov 2 infection pathway. steps", "2 infection pathway. steps of", "infection pathway. steps of sars", "pathway. steps of sars cov", "steps of sars cov 2", "of sars cov 2 genome", "sars cov 2 genome replication", "cov 2 genome replication that", "2 genome replication that have", "genome replication that have been", "replication that have been studied", "that have been studied directly", "have been studied directly include", "been studied directly include binding", "studied directly include binding of", "directly include binding of the", "include binding of the replication", "binding of the replication transcription", "of the replication transcription complex", "replication transcription complex rtc", "complex rtc to", "rtc to the rna", "to the rna template and", "the rna template and the", "rna template and the polymerase", "template and the polymerase activity", "and the polymerase activity of", "the polymerase activity of nsp12", "activity of nsp12 hillen", "of nsp12 hillen et", "nsp12 hillen et al.", "et al. 2020 wang", "al. 2020 wang et", "2020 wang et al.", "et al. 2020 yin", "al. 2020 yin et", "2020 yin et al.", "al. 2020 helicase", "2020 helicase activity", "activity of nsp13 chen", "of nsp13 chen et", "nsp13 chen et al.", "et al. 2020 ji", "al. 2020 ji et", "2020 ji et al.", "et al. 2020 shu", "al. 2020 shu et", "2020 shu et al.", "al. 2020 capping", "2020 capping activity", "activity of nsp16 viswanathan", "of nsp16 viswanathan et", "nsp16 viswanathan et al.", "al. 2020 and", "2020 and polyadenylation", "and polyadenylation of sars cov", "polyadenylation of sars cov 2", "of sars cov 2 genomic", "sars cov 2 genomic rna", "2 genomic rna kim", "genomic rna kim et", "rna kim et al.", "kim et al. 2020 .", "et al. 2020 . replication", "al. 2020 . replication is", "2020 . replication is localized", ". replication is localized in", "replication is localized in double", "is localized in double membrane", "localized in double membrane vesicles", "double membrane vesicles dmvs", "vesicles dmvs that", "dmvs that are created", "that are created by distortion", "are created by distortion of", "created by distortion of er", "by distortion of er membranes", "of er membranes cortese", "er membranes cortese et", "membranes cortese et al", "cortese et al 2020", "al 2020 snijder", "2020 snijder et al", "snijder et al 2020", "et al 2020 .", "al 2020 . one", "2020 . one host factor", ". one host factor needed", "one host factor needed for", "host factor needed for formation", "factor needed for formation of", "needed for formation of these", "for formation of these replication", "formation of these replication organelles", "of these replication organelles is", "these replication organelles is phosphatidic", "replication organelles is phosphatidic acid", "is phosphatidic acid tabata", "phosphatidic acid tabata et", "acid tabata et al", "tabata et al 2021", "et al 2021 .", "al 2021 . other", "2021 . other steps have", ". other steps have been", "other steps have been inferred", "steps have been inferred from", "have been inferred from previous", "been inferred from previous studies", "inferred from previous studies in", "from previous studies in sars", "previous studies in sars cov", "studies in sars cov 1", "in sars cov 1 and", "sars cov 1 and related", "cov 1 and related coronaviruses.

              the", "1 and related coronaviruses.

              the plus", "and related coronaviruses.

              the plus strand", "related coronaviruses.

              the plus strand rna", "coronaviruses.

              the plus strand rna genome", "plus strand rna genome of", "strand rna genome of the", "rna genome of the human", "genome of the human sars", "of the human sars coronavirus", "the human sars coronavirus 1", "sars coronavirus 1 sars", "coronavirus 1 sars cov", "1 sars cov 1", "sars cov 1 is", "cov 1 is replicated", "1 is replicated by", "is replicated by the viral", "replicated by the viral replication", "by the viral replication transcription", "the viral replication transcription complex", "complex rtc composed", "rtc composed of nonstructural", "composed of nonstructural proteins nsp3", "of nonstructural proteins nsp3 nsp16", "proteins nsp3 nsp16 encoded", "nsp3 nsp16 encoded by", "nsp16 encoded by open", "encoded by open reading frames", "by open reading frames orf1a", "open reading frames orf1a and", "reading frames orf1a and orf1b.", "frames orf1a and orf1b. two", "orf1a and orf1b. two rtc", "and orf1b. two rtc proteins", "two rtc proteins nsp8", "rtc proteins nsp8 and", "proteins nsp8 and nsp12", "nsp8 and nsp12 possess", "and nsp12 possess 5'", "nsp12 possess 5' 3'", "possess 5' 3' rna dependent", "5' 3' rna dependent rna", "3' rna dependent rna polymerase", "rna dependent rna polymerase activity.", "dependent rna polymerase activity. nsp12", "rna polymerase activity. nsp12 is", "polymerase activity. nsp12 is the", "activity. nsp12 is the main", "nsp12 is the main rna", "is the main rna polymerase", "main rna polymerase while", "rna polymerase while nsp8", "polymerase while nsp8 is", "while nsp8 is thought to", "nsp8 is thought to act", "is thought to act as", "thought to act as an", "to act as an rna", "act as an rna primase.", "as an rna primase. nsp14", "an rna primase. nsp14 acts", "rna primase. nsp14 acts as", "primase. nsp14 acts as a", "nsp14 acts as a 3'", "acts as a 3' 5'", "as a 3' 5' exonuclease", "3' 5' exonuclease increasing", "5' exonuclease increasing the", "exonuclease increasing the fidelity", "increasing the fidelity of the", "the fidelity of the rtc.", "fidelity of the rtc. nsp14", "of the rtc. nsp14 also", "the rtc. nsp14 also has", "rtc. nsp14 also has the", "nsp14 also has the rna", "also has the rna capping", "has the rna capping activity", "the rna capping activity and", "capping activity and in", "activity and in concert", "and in concert with", "concert with nsp16 it", "with nsp16 it caps", "nsp16 it caps viral", "it caps viral plus strand", "caps viral plus strand and", "viral plus strand and minus", "plus strand and minus strand", "strand and minus strand genomic", "and minus strand genomic and", "minus strand genomic and subgenomic", "strand genomic and subgenomic rnas", "and subgenomic rnas which", "subgenomic rnas which confers", "rnas which confers stability", "which confers stability to viral", "confers stability to viral rnas", "stability to viral rnas by", "to viral rnas by enabling", "viral rnas by enabling them", "rnas by enabling them to", "by enabling them to escape", "enabling them to escape interferon", "them to escape interferon mediated", "to escape interferon mediated innate", "escape interferon mediated innate immune", "interferon mediated innate immune responses", "mediated innate immune responses of", "innate immune responses of the", "immune responses of the host.", "responses of the host. nsp13", "of the host. nsp13 is", "the host. nsp13 is an", "host. nsp13 is an rna", "nsp13 is an rna helicase", "is an rna helicase which", "an rna helicase which is", "rna helicase which is thought", "helicase which is thought to", "which is thought to melt", "is thought to melt secondary", "thought to melt secondary structures", "to melt secondary structures in", "melt secondary structures in the", "secondary structures in the genomic", "structures in the genomic rna", "in the genomic rna during", "the genomic rna during replication", "genomic rna during replication and", "rna during replication and transcription.", "during replication and transcription. the", "replication and transcription. the plus", "and transcription. the plus strand", "transcription. the plus strand genomic", "the plus strand genomic rna", "plus strand genomic rna is", "strand genomic rna is first", "genomic rna is first used", "rna is first used to", "is first used to synthesize", "first used to synthesize the", "used to synthesize the minus", "to synthesize the minus strand", "synthesize the minus strand genomic", "the minus strand genomic rna", "minus strand genomic rna complement", "genomic rna complement which", "rna complement which is", "complement which is subsequently", "which is subsequently used as", "is subsequently used as a", "subsequently used as a template", "used as a template for", "as a template for synthesis", "a template for synthesis of", "template for synthesis of plus", "for synthesis of plus strand", "synthesis of plus strand viral", "of plus strand viral rna", "plus strand viral rna genomes", "strand viral rna genomes that", "viral rna genomes that are", "rna genomes that are packaged", "genomes that are packaged into", "that are packaged into mature", "are packaged into mature virions.", "packaged into mature virions. for", "into mature virions. for review", "virions. for review please", "for review please refer", "review please refer to", "please refer to yang and", "refer to yang and leibowitz", "to yang and leibowitz 2015", "and leibowitz 2015 snijder", "leibowitz 2015 snijder et", "2015 snijder et al.", "et al. 2016 fung", "al. 2016 fung and", "2016 fung and liu" ] }, { "record_id": "GLY_000594_1_1841", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9703465", "r hsa", "hsa 9703465", "r hsa 9703465" ] }, { "record_id": "GLY_000594_1_1841", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by flt3", "flt3 fusion", "fusion proteins", "signaling by flt3", "by flt3 fusion", "flt3 fusion proteins", "signaling by flt3 fusion", "by flt3 fusion proteins", "signaling by flt3 fusion proteins", "in addition", "addition to", "to internal", "internal tandem", "tandem duplications", "duplications and", "and activating", "activating point", "point mutations", "flt3 is", "is also", "also subject", "subject at", "at low", "low frequency", "frequency to", "to translocations", "translocations that", "that generate", "generate fusion", "fusion proteins.", "proteins. these", "these fusion", "proteins occur", "occur in", "in some", "some chronic", "chronic myeloid", "myeloid leukemias", "leukemias as", "as well", "well as", "as myeloid", "myeloid neoplasms", "neoplasms with", "with eosinophilia", "and generate", "generate constitutively", "constitutively active", "active proteins", "proteins by", "by virtue", "virtue of", "of fusing", "fusing a", "a n", "n terminal", "terminal partner", "partner encoding", "encoding a", "a dimerization", "dimerization domain", "domain with", "with the", "the intracellular", "intracellular region", "region of", "of flt3", "reviewed in", "in reiter", "reiter and", "and gotlib", "kazi and", "and roonstrand", "2019 .", ". to", "to date", "6 fusion", "fusion partner", "partner genes", "genes of", "flt3 have", "have been", "been identified:", "identified: etv6", "golgb1 and", "and zmym2", "balwin et", "et al", "vu et", "walz et", "falchi et", "chung et", "troadec et", "grand et", "jawhar et", "zhang et", "2018 .", "in addition to", "addition to internal", "to internal tandem", "internal tandem duplications", "tandem duplications and", "duplications and activating", "and activating point", "activating point mutations", "mutations flt3", "flt3 is also", "is also subject", "also subject at", "subject at low", "at low frequency", "low frequency to", "frequency to translocations", "to translocations that", "translocations that generate", "that generate fusion", "generate fusion proteins.", "fusion proteins. these", "proteins. these fusion", "these fusion proteins", "fusion proteins occur", "proteins occur in", "occur in some", "in some chronic", "some chronic myeloid", "chronic myeloid leukemias", "myeloid leukemias as", "leukemias as well", "as well as", "well as myeloid", "as myeloid neoplasms", "myeloid neoplasms with", "neoplasms with eosinophilia", "eosinophilia and", "and generate constitutively", "generate constitutively active", "constitutively active proteins", "active proteins by", "proteins by virtue", "by virtue of", "virtue of fusing", "of fusing a", "fusing a n", "a n terminal", "n terminal partner", "terminal partner encoding", "partner encoding a", "encoding a dimerization", "a dimerization domain", "dimerization domain with", "domain with the", "with the intracellular", "the intracellular region", "intracellular region of", "region of flt3", "flt3 reviewed", "reviewed in reiter", "in reiter and", "reiter and gotlib", "gotlib 2017", "2017 kazi", "kazi and roonstrand", "roonstrand 2019", "2019 . to", ". to date", "date 6", "6 fusion partner", "fusion partner genes", "partner genes of", "genes of flt3", "of flt3 have", "flt3 have been", "have been identified:", "been identified: etv6", "etv6 trip11", "trip11 myo18a", "myo18a sptbn1", "sptbn1 golgb1", "golgb1 and zmym2", "zmym2 balwin", "balwin et al", "al 2007", "2007 vu", "vu et al", "al 2006", "2006 walz", "walz et al", "al 2011", "2011 falchi", "falchi et al", "al 2014", "2014 chung", "chung et al", "al 2017", "2017 troadec", "troadec et al", "2017 grand", "grand et al", "2007 jawhar", "jawhar et al", "2017 zhang", "zhang et al", "al 2018", "in addition to internal", "addition to internal tandem", "to internal tandem duplications", "internal tandem duplications and", "tandem duplications and activating", "duplications and activating point", "and activating point mutations", "point mutations flt3", "mutations flt3 is", "flt3 is also subject", "is also subject at", "also subject at low", "subject at low frequency", "at low frequency to", "low frequency to translocations", "frequency to translocations that", "to translocations that generate", "translocations that generate fusion", "that generate fusion proteins.", "generate fusion proteins. these", "fusion proteins. these fusion", "proteins. these fusion proteins", "these fusion proteins occur", "fusion proteins occur in", "proteins occur in some", "occur in some chronic", "in some chronic myeloid", "some chronic myeloid leukemias", "chronic myeloid leukemias as", "myeloid leukemias as well", "leukemias as well as", "as well as myeloid", "well as myeloid neoplasms", "as myeloid neoplasms with", "myeloid neoplasms with eosinophilia", "with eosinophilia and", "eosinophilia and generate", "and generate constitutively active", "generate constitutively active proteins", "constitutively active proteins by", "active proteins by virtue", "proteins by virtue of", "by virtue of fusing", "virtue of fusing a", "of fusing a n", "fusing a n terminal", "a n terminal partner", "n terminal partner encoding", "terminal partner encoding a", "partner encoding a dimerization", "encoding a dimerization domain", "a dimerization domain with", "dimerization domain with the", "domain with the intracellular", "with the intracellular region", "the intracellular region of", "intracellular region of flt3", "of flt3 reviewed", "flt3 reviewed in", "reviewed in reiter and", "in reiter and gotlib", "and gotlib 2017", "2017 kazi and", "and roonstrand 2019", "roonstrand 2019 .", "2019 . to date", "to date 6", "date 6 fusion", "6 fusion partner genes", "fusion partner genes of", "partner genes of flt3", "genes of flt3 have", "of flt3 have been", "flt3 have been identified:", "have been identified: etv6", "identified: etv6 trip11", "sptbn1 golgb1 and", "and zmym2 balwin", "zmym2 balwin et", "et al 2007", "2007 vu et", "et al 2006", "2006 walz et", "et al 2011", "2011 falchi et", "et al 2014", "2014 chung et", "et al 2017", "2017 troadec et", "2017 grand et", "2007 jawhar et", "2017 zhang et", "et al 2018", "al 2018 .", "in addition to internal tandem", "addition to internal tandem duplications", "to internal tandem duplications and", "internal tandem duplications and activating", "tandem duplications and activating point", "duplications and activating point mutations", "activating point mutations flt3", "point mutations flt3 is", "mutations flt3 is also", "flt3 is also subject at", "is also subject at low", "also subject at low frequency", "subject at low frequency to", "at low frequency to translocations", "low frequency to translocations that", "frequency to translocations that generate", "to translocations that generate fusion", "translocations that generate fusion proteins.", "that generate fusion proteins. these", "generate fusion proteins. these fusion", "fusion proteins. these fusion proteins", "proteins. these fusion proteins occur", "these fusion proteins occur in", "fusion proteins occur in some", "proteins occur in some chronic", "occur in some chronic myeloid", "in some chronic myeloid leukemias", "some chronic myeloid leukemias as", "chronic myeloid leukemias as well", "myeloid leukemias as well as", "leukemias as well as myeloid", "as well as myeloid neoplasms", "well as myeloid neoplasms with", "as myeloid neoplasms with eosinophilia", "neoplasms with eosinophilia and", "with eosinophilia and generate", "eosinophilia and generate constitutively", "and generate constitutively active proteins", "generate constitutively active proteins by", "constitutively active proteins by virtue", "active proteins by virtue of", "proteins by virtue of fusing", "by virtue of fusing a", "virtue of fusing a n", "of fusing a n terminal", "fusing a n terminal partner", "a n terminal partner encoding", "n terminal partner encoding a", "terminal partner encoding a dimerization", "partner encoding a dimerization domain", "encoding a dimerization domain with", "a dimerization domain with the", "dimerization domain with the intracellular", "domain with the intracellular region", "with the intracellular region of", "the intracellular region of flt3", "region of flt3 reviewed", "of flt3 reviewed in", "flt3 reviewed in reiter", "reviewed in reiter and gotlib", "reiter and gotlib 2017", "gotlib 2017 kazi", "2017 kazi and roonstrand", "kazi and roonstrand 2019", "and roonstrand 2019 .", "roonstrand 2019 . to", ". to date 6", "to date 6 fusion", "date 6 fusion partner", "6 fusion partner genes of", "fusion partner genes of flt3", "partner genes of flt3 have", "genes of flt3 have been", "of flt3 have been identified:", "flt3 have been identified: etv6", "been identified: etv6 trip11", "etv6 trip11 myo18a", "trip11 myo18a sptbn1", "myo18a sptbn1 golgb1", "sptbn1 golgb1 and zmym2", "golgb1 and zmym2 balwin", "and zmym2 balwin et", "zmym2 balwin et al", "balwin et al 2007", "al 2007 vu", "2007 vu et al", "vu et al 2006", "al 2006 walz", "2006 walz et al", "walz et al 2011", "al 2011 falchi", "2011 falchi et al", "falchi et al 2014", "al 2014 chung", "2014 chung et al", "chung et al 2017", "al 2017 troadec", "2017 troadec et al", "troadec et al 2017", "al 2017 grand", "2017 grand et al", "grand et al 2007", "al 2007 jawhar", "2007 jawhar et al", "jawhar et al 2017", "al 2017 zhang", "2017 zhang et al", "zhang et al 2018", "et al 2018 ." ] }, { "record_id": "GLY_000594_1_1842", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9703648", "r hsa", "hsa 9703648", "r hsa 9703648" ] }, { "record_id": "GLY_000594_1_1842", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by flt3", "flt3 itd", "itd and", "and tkd", "tkd mutants", "signaling by flt3", "by flt3 itd", "flt3 itd and", "itd and tkd", "and tkd mutants", "signaling by flt3 itd", "by flt3 itd and", "flt3 itd and tkd", "itd and tkd mutants", "signaling by flt3 itd and", "by flt3 itd and tkd", "flt3 itd and tkd mutants", "flt3 is", "is subject", "subject to", "to internal", "internal 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              at", "
              at lower", "lower frequency", "to activating", "activating point", "point mutations", "~7% of", "of aml", "aml cases", "cases .", "these mutations", "mutations tend", "tend to", "to cluster", "cluster in", "the tkd", "with mutation", "the activation", "activation loop", "loop residue", "residue d835", "d835 and", "and the", "the gatekeeper", "gatekeeper f691", "f691 residue", "residue the", "most common", "common sites", "griffin et", "jiang et", ".
              flt3", "
              flt3 itd", "mutants support", "support cellular", "cellular transformation", "transformation through", "through activation", "activation of", "of downstream", "downstream signaling", "signaling pathways", "pathways such", "such as", "as the", "the map", "map kinase", "pi3k/akt and", "and stat5", "stat5 cascades.", "cascades. there", "there is", "is some", "some debate", "debate about", "about the", "the extent", "extent to", "to which", "which the", "the pathways", "pathways activated", "activated by", "by the", "the itd", "mutants are", "are distinct", "with some", "some evidence", "evidence that", "that stat5", "stat5 signaling", "in particular", "is more", "more characteristic", "characteristic of", "of flt3", "itd activation", "hayakawa et", "choudhary et", "grundler et", "yoshimoto et", "leischner et", "janke et", "marhall et", "in chan", "flt3 is subject", "is subject to", "subject to internal", "to internal tandem", "internal tandem duplications", "duplications itds", "itds of", "of lengths varying", "lengths varying from", "varying from 3", "from 3 to", "3 to 1236", "to 1236 base", "1236 base pairs", "pairs nakao", "nakao et al", "al 1996", "1996 kiyoi", "kiyoi et al", "et al 1997", "1997 meshinchi", "meshinchi et al", "al 2008", "2008 reviewed", "reviewed in kazi", "in kazi and", "kazi and roonstrand", "roonstrand 2019", "2019 . these", ". these itds", "these itds are", "itds are generally", "are generally found", "generally found in", "found in the", "in the juxtamembrane", "the juxtamembrane domain", "domain or", "or more rarely", "rarely the", "the first tyrosine", "first tyrosine kinase", "tyrosine kinase domain", "domain tkd", "tkd and", "and disrupt the", "disrupt the autoinhibitory", "the autoinhibitory loop", "autoinhibitory loop of", "loop of the", "of the receptor", "receptor constitutively", "constitutively activating it", "it kiyoi", "al 2002", "2002 griffith", "griffith et al", "al 2004", "2004 reviewed", "reviewed in lagunas", "in lagunas rangel", "lagunas rangel and", "rangel and chavez", "and chavez valencia", "valencia 2017", "2017 kazi", "2019 . flt3", ". flt3 itds", "flt3 itds are", "itds are found", "are found in", "found in ~25%", "in ~25% of", "~25% of acute", "of acute myeloid", "acute myeloid leukemias", "leukemias amls", "amls and", "and represent the", "represent the most", "the most frequent", "most frequent mutation", "frequent mutation of", "mutation of this", "of this cancer", "cancer reviewed", "2019 klug", "klug et al", "al 2018", "2018
              at lower", "
              at lower frequency", "frequency flt3", "subject to activating", "to activating point", "activating point mutations", "mutations ~7%", "~7% of aml", "of aml cases", "aml cases .", "cases . these", ". these mutations", "these mutations tend", "mutations tend to", "tend to cluster", "to cluster in", "cluster in the", "in the tkd", "tkd with", "with mutation of", "mutation of the", "of the activation", "the activation loop", "activation loop residue", "loop residue d835", "residue d835 and", "d835 and the", "and the gatekeeper", "the gatekeeper f691", "gatekeeper f691 residue", "f691 residue the", "residue the most", "the most common", "most common sites", "sites griffin", "griffin et al", "al 2001", "2001 jiang", "jiang et al", "2019 .
              flt3", ".
              flt3 itd", "
              flt3 itd and", "tkd mutants support", "mutants support cellular", "support cellular transformation", "cellular transformation through", "transformation through activation", "through activation of", "activation of downstream", "of downstream signaling", "downstream signaling pathways", "signaling pathways such", "pathways such as", "such as the", "as the map", "the map kinase", "kinase pi3k/akt", "pi3k/akt and stat5", "and stat5 cascades.", "stat5 cascades. there", "cascades. there is", "there is some", "is some debate", "some debate about", "debate about the", "about the extent", "the extent to", "extent to which", "to which the", "which the pathways", "the pathways activated", "pathways activated by", "activated by the", "by the itd", "the itd and", "tkd mutants are", "mutants are distinct", "distinct with", "with some evidence", "some evidence that", "evidence that stat5", "that stat5 signaling", "signaling in", "particular is", "is more characteristic", "more characteristic of", "characteristic of flt3", "of flt3 itd", "flt3 itd activation", "activation hayakawa", "hayakawa et al", "al 2000", "2000 choudhary", "choudhary et al", "al 2005", "2005 grundler", "grundler et al", "2005 choudhary", "al 2007", "2007 yoshimoto", "yoshimoto et al", "al 2009", "2009 leischner", "leischner et al", "al 2012", "2012 janke", "janke et al", "al 2014", "2014 marhall", "marhall et al", "2018 reviewed", "reviewed in chan", "chan 2011", "2011 kazi", "flt3 is subject to", "is subject to internal", "subject to internal tandem", "to internal tandem duplications", "tandem duplications itds", "itds of lengths", "of lengths varying from", "lengths varying from 3", "varying from 3 to", "from 3 to 1236", "3 to 1236 base", "to 1236 base pairs", "base pairs nakao", "pairs nakao et", "et al 1996", "1996 kiyoi et", "kiyoi et al 1997", "al 1997 meshinchi", "1997 meshinchi et", "et al 2008", "2008 reviewed in", "reviewed in kazi and", "in kazi and roonstrand", "and roonstrand 2019", "roonstrand 2019 .", "2019 . these itds", ". these itds are", "these itds are generally", "itds are generally found", "are generally found in", "generally found in the", "found in the juxtamembrane", "in the juxtamembrane domain", "juxtamembrane domain or", "domain or more", "more rarely the", "rarely the first", "the first tyrosine kinase", "first tyrosine kinase domain", "kinase domain tkd", "tkd and disrupt", "and disrupt the autoinhibitory", "disrupt the autoinhibitory loop", "the autoinhibitory loop of", "autoinhibitory loop of the", "loop of the receptor", "the receptor constitutively", "receptor constitutively activating", "activating it kiyoi", "it kiyoi et", "et al 2002", "2002 griffith et", "et al 2004", "2004 reviewed in", "reviewed in lagunas rangel", "in lagunas rangel and", "lagunas rangel and chavez", "rangel and chavez valencia", "chavez valencia 2017", "2017 kazi and", "2019 . flt3 itds", ". flt3 itds are", "flt3 itds are found", "itds are found in", "are found in ~25%", "found in ~25% of", "in ~25% of acute", "~25% of acute myeloid", "of acute myeloid leukemias", "myeloid leukemias amls", "amls and represent", "and represent the most", "represent the most frequent", "the most frequent mutation", "most frequent mutation of", "frequent mutation of this", "mutation of this cancer", "this cancer reviewed", "cancer reviewed in", "2019 klug et", "et al 2018", "al 2018
              at", "2018
              at lower frequency", "lower frequency flt3", "frequency flt3 is", "is subject to activating", "subject to activating point", "to activating point mutations", "point mutations ~7%", "mutations ~7% of", "~7% of aml cases", "of aml cases .", "aml cases . these", "cases . these mutations", ". these mutations tend", "these mutations tend to", "mutations tend to cluster", "tend to cluster in", "to cluster in the", "cluster in the tkd", "the tkd with", "tkd with mutation", "with mutation of the", "mutation of the activation", "of the activation loop", "the activation loop residue", "activation loop residue d835", "loop residue d835 and", "residue d835 and the", "d835 and the gatekeeper", "and the gatekeeper f691", "the gatekeeper f691 residue", "gatekeeper f691 residue the", "f691 residue the most", "residue the most common", "the most common sites", "common sites griffin", "sites griffin et", "et al 2001", "2001 jiang et", "2019 .
              flt3 itd", ".
              flt3 itd and", "
              flt3 itd and tkd", "and tkd mutants support", "tkd mutants support cellular", "mutants support cellular transformation", "support cellular transformation through", "cellular transformation through activation", "transformation through activation of", "through activation of downstream", "activation of downstream signaling", "of downstream signaling pathways", "downstream signaling pathways such", "signaling pathways such as", "pathways such as the", "such as the map", "as the map kinase", "map kinase pi3k/akt", "kinase pi3k/akt and", "pi3k/akt and stat5 cascades.", "and stat5 cascades. there", "stat5 cascades. there is", "cascades. there is some", "there is some debate", "is some debate about", "some debate about the", "debate about the extent", "about the extent to", "the extent to which", "extent to which the", "to which the pathways", "which the pathways activated", "the pathways activated by", "pathways activated by the", "activated by the itd", "by the itd and", "the itd and tkd", "and tkd mutants are", "tkd mutants are distinct", "are distinct with", "distinct with some", "with some evidence that", "some evidence that stat5", "evidence that stat5 signaling", "stat5 signaling in", "signaling in particular", "in particular is", "particular is more", "is more characteristic of", "more characteristic of flt3", "characteristic of flt3 itd", "of flt3 itd activation", "itd activation hayakawa", "activation hayakawa et", "et al 2000", "2000 choudhary et", "et al 2005", "2005 grundler et", "2005 choudhary et", "et al 2007", "2007 yoshimoto et", "et al 2009", "2009 leischner et", "et al 2012", "2012 janke et", "et al 2014", "2014 marhall et", "2018 reviewed in", "in chan 2011", "2011 kazi and", "flt3 is subject to internal", "is subject to internal tandem", "subject to internal tandem duplications", "internal tandem duplications itds", "duplications itds of", "itds of lengths varying", "of lengths varying from 3", "lengths varying from 3 to", "varying from 3 to 1236", "from 3 to 1236 base", "3 to 1236 base pairs", "1236 base pairs nakao", "base pairs nakao et", "pairs nakao et al", "nakao et al 1996", "al 1996 kiyoi", "1996 kiyoi et al", "et al 1997 meshinchi", "al 1997 meshinchi et", "1997 meshinchi et al", "meshinchi et al 2008", "al 2008 reviewed", "2008 reviewed in kazi", "reviewed in kazi and roonstrand", "kazi and roonstrand 2019", "and roonstrand 2019 .", "roonstrand 2019 . these", "2019 . these itds are", ". these itds are generally", "these itds are generally found", "itds are generally found in", "are generally found in the", "generally found in the juxtamembrane", "found in the juxtamembrane domain", "the juxtamembrane domain or", "juxtamembrane domain or more", "domain or more rarely", "or more rarely the", "more rarely the first", "rarely the first tyrosine", "the first tyrosine kinase domain", "tyrosine kinase domain tkd", "domain tkd and", "tkd and disrupt the", "and disrupt the autoinhibitory loop", "disrupt the autoinhibitory loop of", "the autoinhibitory loop of the", "autoinhibitory loop of the receptor", "of the receptor constitutively", "the receptor constitutively activating", "receptor constitutively activating it", "constitutively activating it kiyoi", "activating it kiyoi et", "it kiyoi et al", "kiyoi et al 2002", "al 2002 griffith", "2002 griffith et al", "griffith et al 2004", "al 2004 reviewed", "2004 reviewed in lagunas", "reviewed in lagunas rangel and", "in lagunas rangel and chavez", "lagunas rangel and chavez valencia", "and chavez valencia 2017", "valencia 2017 kazi", "2017 kazi and roonstrand", "roonstrand 2019 . flt3", "2019 . flt3 itds are", ". flt3 itds are found", "flt3 itds are found in", "itds are found in ~25%", "are found in ~25% of", "found in ~25% of acute", "in ~25% of acute myeloid", "~25% of acute myeloid leukemias", "acute myeloid leukemias amls", "leukemias amls and", "amls and represent the", "and represent the most frequent", "represent the most frequent mutation", "the most frequent mutation of", "most frequent mutation of this", "frequent mutation of this cancer", "of this cancer reviewed", "this cancer reviewed in", "cancer reviewed in kazi", "roonstrand 2019 klug", "2019 klug et al", "klug et al 2018", "et al 2018
              at", "al 2018
              at lower", "
              at lower frequency flt3", "lower frequency flt3 is", "frequency flt3 is subject", "flt3 is subject to activating", "is subject to activating point", "subject to activating point mutations", "activating point mutations ~7%", "point mutations ~7% of", "mutations ~7% of aml", "~7% of aml cases .", "of aml cases . these", "aml cases . these mutations", "cases . these mutations tend", ". these mutations tend to", "these mutations tend to cluster", "mutations tend to cluster in", "tend to cluster in the", "to cluster in the tkd", "in the tkd with", "the tkd with mutation", "tkd with mutation of", "with mutation of the activation", "mutation of the activation loop", "of the activation loop residue", "the activation loop residue d835", "activation loop residue d835 and", "loop residue d835 and the", "residue d835 and the gatekeeper", "d835 and the gatekeeper f691", "and the gatekeeper f691 residue", "the gatekeeper f691 residue the", "gatekeeper f691 residue the most", "f691 residue the most common", "residue the most common sites", "most common sites griffin", "common sites griffin et", "sites griffin et al", "griffin et al 2001", "al 2001 jiang", "2001 jiang et al", "jiang et al 2004", "2004 reviewed in kazi", "roonstrand 2019 .
              flt3", "2019 .
              flt3 itd and", ".
              flt3 itd and tkd", "
              flt3 itd and tkd mutants", "itd and tkd mutants support", "and tkd mutants support cellular", "tkd mutants support cellular transformation", "mutants support cellular transformation through", "support cellular transformation through activation", "cellular transformation through activation of", "transformation through activation of downstream", "through activation of downstream signaling", "activation of downstream signaling pathways", "of downstream signaling pathways such", "downstream signaling pathways such as", "signaling pathways such as the", "pathways such as the map", "such as the map kinase", "the map kinase pi3k/akt", "map kinase pi3k/akt and", "kinase pi3k/akt and stat5", "pi3k/akt and stat5 cascades. there", "and stat5 cascades. there is", "stat5 cascades. there is some", "cascades. there is some debate", "there is some debate about", "is some debate about the", "some debate about the extent", "debate about the extent to", "about the extent to which", "the extent to which the", "extent to which the pathways", "to which the pathways activated", "which the pathways activated by", "the pathways activated by the", "pathways activated by the itd", "activated by the itd and", "by the itd and tkd", "the itd and tkd mutants", "itd and tkd mutants are", "and tkd mutants are distinct", "mutants are distinct with", "are distinct with some", "distinct with some evidence", "with some evidence that stat5", "some evidence that stat5 signaling", "that stat5 signaling in", "stat5 signaling in particular", "in particular is more", "particular is more characteristic", "is more characteristic of flt3", "more characteristic of flt3 itd", "characteristic of flt3 itd activation", "flt3 itd activation hayakawa", "itd activation hayakawa et", "activation hayakawa et al", "hayakawa et al 2000", "al 2000 choudhary", "2000 choudhary et al", "choudhary et al 2005", "al 2005 grundler", "2005 grundler et al", "grundler et al 2005", "al 2005 choudhary", "2005 choudhary et al", "choudhary et al 2007", "al 2007 yoshimoto", "2007 yoshimoto et al", "yoshimoto et al 2009", "al 2009 leischner", "2009 leischner et al", "leischner et al 2012", "al 2012 janke", "2012 janke et al", "janke et al 2014", "al 2014 marhall", "2014 marhall et al", "marhall et al 2018", "al 2018 reviewed", "2018 reviewed in chan", "reviewed in chan 2011", "chan 2011 kazi", "2011 kazi and roonstrand" ] }, { "record_id": "GLY_000594_1_1843", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9706374", "r hsa", "hsa 9706374", "r hsa 9706374" ] }, { "record_id": "GLY_000594_1_1843", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "flt3 signaling", "signaling through", "through src", "src family", "family kinases", "flt3 signaling through", "signaling through src", "through src family", "src family kinases", "flt3 signaling through src", "signaling through src family", "through src family kinases", "flt3 signaling through src family", "signaling through src family kinases", "several src", "have been", "been shown", "shown to", "to interact", "interact with", "with active", "active flt3", "flt3 to", "to modulate", "modulate downstream", "downstream signaling.", "signaling. these", "these include", "include fyn", "lck and", "and syk", "heiss et", "et al", "mitina et", "chougule et", "dosil et", "marhall et", "puissant et", "reviewed in", "in kazi", "kazi and", "and ronnstrand", "2019a b", "b .", ". the", "the role", "role of", "of sfks", "sfks downstream", "downstream of", "of flt3", "flt3 is", "is complex", "complex and", "and not", "not fully", "fully elucidated.", "elucidated. some", "some family", "family members", "members appear", "appear to", "to contribute", "contribute positively", "positively to", "to signaling", "as assessed", "assessed by", "by elevated", "elevated stat5", "stat5 signaling", "while others", "others may", "may contribute", "contribute to", "to ubiquitin", "ubiquitin ligation", "ligation and", "and downregulation", "downregulation of", "of the", "the receptor", "receptor through", "through interaction", "interaction with", "with cbl", ".

              ", "several src family", "kinases sfks", "sfks have", "have been shown", "been shown to", "shown to interact", "to interact with", "interact with active", "with active flt3", "active flt3 to", "flt3 to modulate", "to modulate downstream", "modulate downstream signaling.", "downstream signaling. these", "signaling. these include", "these include fyn", "fyn hck", "hck lck", "lck and syk", "syk heiss", "heiss et al", "al 2006", "2006 mitina", "mitina et al", "al 2007", "2007 chougule", "chougule et al", "al 2016", "2016 dosil", "dosil et al", "al 1993", "1993 marhall", "marhall et al", "al 2017", "2017 puissant", "puissant et al", "al 2014", "2014 reviewed", "reviewed in kazi", "in kazi and", "kazi and ronnstrand", "ronnstrand 2019a", "2019a b .", "b . the", ". the role", "the role of", "role of sfks", "of sfks downstream", "sfks downstream of", "downstream of flt3", "of flt3 is", "flt3 is complex", "is complex and", "complex and not", "and not fully", "not fully elucidated.", "fully elucidated. some", "elucidated. some family", "some family members", "family members appear", "members appear to", "appear to contribute", "to contribute positively", "contribute positively to", "positively to signaling", "signaling as", "as assessed by", "assessed by elevated", "by elevated stat5", "elevated stat5 signaling", "signaling while", "while others may", "others may contribute", "may contribute to", "contribute to ubiquitin", "to ubiquitin ligation", "ubiquitin ligation and", "ligation and downregulation", "and downregulation of", "downregulation of the", "of the receptor", "the receptor through", "receptor through interaction", "through interaction with", "interaction with cbl", "cbl chougule", "2016 heiss", "2006 marhall", "2017 reviewed", "b .

              ", "several src family kinases", "family kinases sfks", "sfks have been", "have been shown to", "been shown to interact", "shown to interact with", "to interact with active", "interact with active flt3", "with active flt3 to", "active flt3 to modulate", "flt3 to modulate downstream", "to modulate downstream signaling.", "modulate downstream signaling. these", "downstream signaling. these include", "signaling. these include fyn", "include fyn hck", "hck lck and", "and syk heiss", "syk heiss et", "et al 2006", "2006 mitina et", "et al 2007", "2007 chougule et", "et al 2016", "2016 dosil et", "et al 1993", "1993 marhall et", "et al 2017", "2017 puissant et", "et al 2014", "2014 reviewed in", "reviewed in kazi and", "in kazi and ronnstrand", "and ronnstrand 2019a", "ronnstrand 2019a b", "2019a b . the", "b . the role", ". the role of", "the role of sfks", "role of sfks downstream", "of sfks downstream of", "sfks downstream of flt3", "downstream of flt3 is", "of flt3 is complex", "flt3 is complex and", "is complex and not", "complex and not fully", "and not fully elucidated.", "not fully elucidated. some", "fully elucidated. some family", "elucidated. some family members", "some family members appear", "family members appear to", "members appear to contribute", "appear to contribute positively", "to contribute positively to", "contribute positively to signaling", "to signaling as", "signaling as assessed", "as assessed by elevated", "assessed by elevated stat5", "by elevated stat5 signaling", "stat5 signaling while", "signaling while others", "while others may contribute", "others may contribute to", "may contribute to ubiquitin", "contribute to ubiquitin ligation", "to ubiquitin ligation and", "ubiquitin ligation and downregulation", "ligation and downregulation of", "and downregulation of the", "downregulation of the receptor", "of the receptor through", "the receptor through interaction", "receptor through interaction with", "through interaction with cbl", "with cbl chougule", "cbl chougule et", "2016 heiss et", "2006 marhall et", "2017 reviewed in", "2019a b .

              ", "src family kinases sfks", "kinases sfks have", "sfks have been shown", "have been shown to interact", "been shown to interact with", "shown to interact with active", "to interact with active flt3", "interact with active flt3 to", "with active flt3 to modulate", "active flt3 to modulate downstream", "flt3 to modulate downstream signaling.", "to modulate downstream signaling. these", "modulate downstream signaling. these include", "downstream signaling. these include fyn", "these include fyn hck", "fyn hck lck", "hck lck and syk", "lck and syk heiss", "and syk heiss et", "syk heiss et al", "heiss et al 2006", "al 2006 mitina", "2006 mitina et al", "mitina et al 2007", "al 2007 chougule", "2007 chougule et al", "chougule et al 2016", "al 2016 dosil", "2016 dosil et al", "dosil et al 1993", "al 1993 marhall", "1993 marhall et al", "marhall et al 2017", "al 2017 puissant", "2017 puissant et al", "puissant et al 2014", "al 2014 reviewed", "2014 reviewed in kazi", "reviewed in kazi and ronnstrand", "kazi and ronnstrand 2019a", "and ronnstrand 2019a b", "ronnstrand 2019a b .", "2019a b . the role", "b . the role of", ". the role of sfks", "the role of sfks downstream", "role of sfks downstream of", "of sfks downstream of flt3", "sfks downstream of flt3 is", "downstream of flt3 is complex", "of flt3 is complex and", "flt3 is complex and not", "is complex and not fully", "complex and not fully elucidated.", "and not fully elucidated. some", "not fully elucidated. some family", "fully elucidated. some family members", "elucidated. some family members appear", "some family members appear to", "family members appear to contribute", "members appear to contribute positively", "appear to contribute positively to", "to contribute positively to signaling", "positively to signaling as", "to signaling as assessed", "signaling as assessed by", "as assessed by elevated stat5", "assessed by elevated stat5 signaling", "elevated stat5 signaling while", "stat5 signaling while others", "signaling while others may", "while others may contribute to", "others may contribute to ubiquitin", "may contribute to ubiquitin ligation", "contribute to ubiquitin ligation and", "to ubiquitin ligation and downregulation", "ubiquitin ligation and downregulation of", "ligation and downregulation of the", "and downregulation of the receptor", "downregulation of the receptor through", "of the receptor through interaction", "the receptor through interaction with", "receptor through interaction with cbl", "interaction with cbl chougule", "with cbl chougule et", "cbl chougule et al", "al 2016 heiss", "2016 heiss et al", "al 2006 marhall", "2006 marhall et al", "al 2017 reviewed", "2017 reviewed in kazi" ] }, { "record_id": "GLY_000594_1_1844", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9708296", "r hsa", "hsa 9708296", "r hsa 9708296" ] }, { "record_id": "GLY_000594_1_1844", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "trna derived", "derived small", "small rna", "tsrna or", "or trna", "trna related", "related fragment", "trna derived small", "derived small rna", "rna tsrna", "tsrna or trna", "or trna related", "trna related fragment", "fragment trf", "trf biogenesis", "trna derived small rna", "small rna tsrna", "rna tsrna or", "tsrna or trna related", "or trna related fragment", "related fragment trf", "derived small rna tsrna", "small rna tsrna or", "rna tsrna or trna", "tsrna or trna related fragment", "trna related fragment trf", "fragment trf biogenesis", "defined fragments", "fragments of", "of trnas", "termed trna\u2011derived", "trna\u2011derived small", "small rnas", "have been", "been observed", "observed in", "in particular", "particular cell", "cell types", "types and", "and in", "in response", "response to", "to biological", "biological conditions", "conditions such", "such as", "as exposure", "exposure to", "to sex", "sex hormone", "hormone or", "or stresses", "stresses such", "as hypoxia", "oxidative stress", "and virus", "virus infection", "reviewed in", "in keam", "keam and", "and hutvagner", "hutvagner 2015", "kumar et", "et al.", "al. 2016", "oberbauer and", "and schaefer", "schaefer 2018", "park et", "al. 2020", "su et", "xie et", "zhu et", "2020 .", ". rather", "rather than", "than being", "being the", "the random", "random products", "products of", "of trna", "trna degradation", "tsrnas appear", "appear to", "to be", "be the", "the specific", "specific products", "of ribonucleases.", "ribonucleases. two", "two categories", "categories of", "of trna\u2011derived", "been described:", "tsrnas known", "known as", "as trna", "trna halves", "halves or", "or stress\u2011induced", "stress\u2011induced tsrnas", "that are", "are produced", "produced by", "by single", "single cleavage", "cleavage of", "trnas within", "within or", "or near", "near the", "the anticodon", "anticodon and", "15\u201130 nt", "tsrnas termed", "termed trna", "related fragments", "that result", "result from", "from cleavage", "cleavage closer", "closer to", "to the", "the 5'", "5' or", "or 3'", "3' end", "end of", "of the", "the trna.", "trna. trf", "trf 3s", "3s are", "are derived", "derived from", "from the", "the 3'", "3' region", "region of", "the trna", "approximately the", "the region", "region from", "the t", "t loop", "loop to", "3' terminus.", "terminus. trf", "trf 5s", "5s are", "5' region", "the d", "d loop", "5' terminus.", "terminus. trf2\u2011type", "trf2\u2011type trfs", "also called", "called internal", "internal trfs", "the central", "central region", "region between", "between the", "loop and", "and the", "and containing", "containing the", "the anticodon.", "anticodon. trf", "trf 1s", "also known", "as type", "type ii", "ii trfs", "trfs or", "or 3\u2019u", "3\u2019u trfs", "are the", "3' trailers", "trailers of", "of particular", "particular trnas", "trnas that", "that persist", "persist after", "after processing.
              in", "processing.
              in most", "most cases", "cases the", "the enzymes", "enzymes responsible", "responsible for", "for the", "the cleavages", "cleavages are", "are not", "not yet", "yet known", "however several", "several ribonucleases", "ribonucleases involved", "involved in", "in cleavage", "trna have", "been identified:", "identified: the", "the secreted", "secreted and", "and endocytosed", "endocytosed ribonuclease", "ribonuclease a", "a family", "family members", "members angiogenin", "and rnase", "rnase 1", "the interferon", "interferon induced", "induced ribonucleases", "ribonucleases rnase", "rnase l", "schlafen 11", "and schlafen13", "slfn13 or", "or rnase", "rnase s13", "the cytosolic", "cytosolic ribonuclease", "ribonuclease iii\u2011like", "double strand", "strand rna\u2011specific", "enzyme dicer1", "the rna", "rna processing", "processing enzyme", "enzyme elac2.", "elac2. ang", "ang is", "is secreted", "binds receptors", "receptors on", "on cell", "cell membranes", "is endocytosed", "and translocates", "translocates to", "the nucleus.", "nucleus. ang", "ang cleaves", "cleaves within", "within the", "anticodon loop", "to produce", "produce trna", "halves and", "the cleavage", "cleavage is", "is thought", "thought to", "to occur", "occur while", "while ang", "is transiently", "transiently located", "located in", "in the", "the cytosol", "lee and", "and vallee", "vallee 1989", "saxena et", "al. 1992", "fu et", "al. 2009", "yamasaki et", "emara et", "al. 2010", "ivanov et", "al. 2011", "2011 .", ". cleavage", "cleavage by", "by ang", "is observed", "to cellular", "cellular stresses", "as starvation", ". however", "ang knockout", "knockout cells", "cells continue", "continue to", "produce stress", "stress induced", "induced trna", "suggesting that", "that other", "other enzymes", "enzymes are", "are also", "also involved", "in producing", "producing the", "the halves", "al. 2019", "2019 .", "similar to", "to ang", "ang as", "as an", "an rnase", "rnase a", "a member", "secreted endoribonuclease", "endoribonuclease rnase", "1 cleaves", "cleaves trnas", "trnas at", "at the", "loop in", "the extracellular", "extracellular space", "nechooshtan et", "2020 .
              ", ".
              interferon", "induced rnases", "rnases can", "can also", "also cleave", "cleave trnas.", "trnas. rnase", "l is", "is responsive", "responsive to", "to double", "double stranded", "stranded rnas", "rnas and", "and cleaves", "cleaves at", "trna anticodon", "donovan et", "al. 2017", "2017 .", ". schlafen", "schlafen family", "members slfn11", "slfn11 and", "and slfn13", "slfn13 can", "cleave trnas", "li et", "al. 2018", "yang et", "2018 .
              dicer1", ".
              dicer1 cleaves", "cleaves double\u2011stranded", "double\u2011stranded regions", "regions of", "trnas near", "5' terminus", "terminus or", "3' terminus", "terminus to", "produce short", "short trfs", "cole et", "yeung et", "maute et", "al. 2013", "hasler et", "2016 .", ". the", "the mechanism", "mechanism that", "that dissociates", "dissociates the", "the double\u2011stranded", "double\u2011stranded products", "of dicer1", "dicer1 to", "to yield", "yield single\u2011stranded", "single\u2011stranded trfs", "trfs may", "may be", "the same", "same as", "as that", "that for", "for mirnas", "but this", "this has", "has not", "yet been", "been demonstrated.", "demonstrated. furthermore", "the bulk", "bulk of", "the short", "trfs is", "is still", "still detected", "detected in", "in dicer1", "dicer1 null", "null cells", "kumar 2014", "kuscu &", "& kumar", "suggesting other", "other unknown", "unknown factors", "factors are", "are involved", "in their", "their biogenesis.", "biogenesis. elac2", "elac2 in", "cytosol cleaves", "cleaves the", "of precursors", "precursors of", "trna ser", "ser tga", "ser gtc", "and trna", "trna asp", "asp gtc", "lee et", "2009 .", "the trailers", "called trf", "then persist", "persist in", "al. 2014", "2014 .", "defined fragments of", "fragments of trnas", "trnas termed", "termed trna\u2011derived small", "trna\u2011derived small rnas", "rnas tsrnas", "have been observed", "been observed in", "observed in particular", "in particular cell", "particular cell types", "cell types and", "types and in", "and in response", "in response to", "response to biological", "to biological conditions", "biological conditions such", "conditions such as", "such as exposure", "as exposure to", "exposure to sex", "to sex hormone", "sex hormone or", "hormone or stresses", "or stresses such", "stresses such as", "such as hypoxia", "hypoxia starvation", "starvation oxidative", "stress and", "and virus infection", "infection reviewed", "reviewed in keam", "in keam and", "keam and hutvagner", "and hutvagner 2015", "2015 kumar", "kumar et al.", "et al. 2016", "2016 oberbauer", "oberbauer and schaefer", "and schaefer 2018", "2018 park", "park et al.", "et al. 2020", "2020 su", "su et al.", "2020 xie", "xie et al.", "2020 zhu", "zhu et al.", "al. 2020 .", "2020 . rather", ". rather than", "rather than being", "than being the", "being the random", "the random products", "random products of", "products of trna", "of trna degradation", "degradation tsrnas", "tsrnas appear to", "appear to be", "to be the", "be the specific", "the specific products", "specific products of", "products of ribonucleases.", "of ribonucleases. two", "ribonucleases. two categories", "two categories of", "categories of trna\u2011derived", "of trna\u2011derived small", "tsrnas have", "have been described:", "described: 1", "1 longer", "longer 31\u201140nt", "31\u201140nt tsrnas", "tsrnas known as", "known as trna", "as trna halves", "trna halves or", "halves or stress\u2011induced", "or stress\u2011induced tsrnas", "tsrnas tirnas", "tirnas that", "that are produced", "are produced by", "produced by single", "by single cleavage", "single cleavage of", "cleavage of trnas", "of trnas within", "trnas within or", "within or near", "or near the", "near the anticodon", "the anticodon and", "and 2", "2 shorter", "shorter 15\u201130", "nt tsrnas", "tsrnas termed trna", "termed trna related", "trna related fragments", "fragments trfs", "trfs that", "that result from", "result from cleavage", "from cleavage closer", "cleavage closer to", "closer to the", "to the 5'", "the 5' or", "5' or 3'", "or 3' end", "3' end of", "end of the", "of the trna.", "the trna. trf", "trna. trf 3s", "trf 3s are", "3s are derived", "are derived from", "derived from the", "from the 3'", "the 3' region", "3' region of", "region of the", "of the trna", "trna approximately", "approximately the region", "the region from", "region from the", "from the t", "the t loop", "t loop to", "loop to the", "to the 3'", "the 3' terminus.", "3' terminus. trf", "terminus. trf 5s", "trf 5s are", "5s are derived", "from the 5'", "the 5' region", "5' region of", "from the d", "the d loop", "d loop to", "the 5' terminus.", "5' terminus. trf2\u2011type", "terminus. trf2\u2011type trfs", "trfs also", "also called internal", "called internal trfs", "trfs are", "from the central", "the central region", "central region of", "the region between", "region between the", "between the d", "d loop and", "loop and the", "and the t", "t loop and", "loop and containing", "and containing the", "containing the anticodon.", "the anticodon. trf", "anticodon. trf 1s", "1s also", "also known as", "known as type", "as type ii", "type ii trfs", "ii trfs or", "trfs or 3\u2019u", "or 3\u2019u trfs", "are the 3'", "the 3' trailers", "3' trailers of", "trailers of particular", "of particular trnas", "particular trnas that", "trnas that persist", "that persist after", "persist after processing.
              in", "after processing.
              in most", "processing.
              in most cases", "most cases the", "cases the enzymes", "the enzymes responsible", "enzymes responsible for", "responsible for the", "for the cleavages", "the cleavages are", "cleavages are not", "are not yet", "not yet known", "known however", "however several ribonucleases", "several ribonucleases involved", "ribonucleases involved in", "involved in cleavage", "in cleavage of", "cleavage of trna", "of trna have", "trna have been", "have been identified:", "been identified: the", "identified: the secreted", "the secreted and", "secreted and endocytosed", "and endocytosed ribonuclease", "endocytosed ribonuclease a", "ribonuclease a family", "a family members", "family members angiogenin", "angiogenin ang", "ang and", "and rnase 1", "1 the", "the interferon induced", "interferon induced ribonucleases", "induced ribonucleases rnase", "ribonucleases rnase l", "l schlafen", "11 slfn11", "schlafen13 slfn13", "slfn13 or rnase", "or rnase s13", "the cytosolic ribonuclease", "cytosolic ribonuclease iii\u2011like", "iii\u2011like double", "double strand rna\u2011specific", "rna\u2011specific enzyme", "dicer1 and", "and the rna", "the rna processing", "rna processing enzyme", "processing enzyme elac2.", "enzyme elac2. ang", "elac2. ang is", "ang is secreted", "secreted binds", "binds receptors on", "receptors on cell", "on cell membranes", "membranes is", "endocytosed and", "and translocates to", "translocates to the", "to the nucleus.", "the nucleus. ang", "nucleus. ang cleaves", "ang cleaves within", "cleaves within the", "within the anticodon", "the anticodon loop", "anticodon loop to", "loop to produce", "to produce trna", "produce trna halves", "trna halves and", "halves and the", "and the cleavage", "the cleavage is", "cleavage is thought", "is thought to", "thought to occur", "to occur while", "occur while ang", "while ang is", "ang is transiently", "is transiently located", "transiently located in", "located in the", "in the cytosol", "cytosol lee", "lee and vallee", "and vallee 1989", "1989 saxena", "saxena et al.", "et al. 1992", "1992 fu", "fu et al.", "et al. 2009", "2009 yamasaki", "yamasaki et al.", "2009 emara", "emara et al.", "et al. 2010", "2010 ivanov", "ivanov et al.", "et al. 2011", "al. 2011 .", "2011 . cleavage", ". cleavage by", "cleavage by ang", "by ang is", "ang is observed", "is observed in", "observed in response", "response to cellular", "to cellular stresses", "cellular stresses such", "such as starvation", "starvation fu", "2011 . however", "however ang", "ang knockout cells", "knockout cells continue", "cells continue to", "continue to produce", "to produce stress", "produce stress induced", "stress induced trna", "induced trna halves", "halves suggesting", "suggesting that other", "that other enzymes", "other enzymes are", "enzymes are also", "are also involved", "also involved in", "involved in producing", "in producing the", "producing the halves", "halves su", "et al. 2019", "al. 2019 .", ". similar", "similar to ang", "to ang as", "ang as an", "as an rnase", "an rnase a", "rnase a member", "member the", "the secreted endoribonuclease", "secreted endoribonuclease rnase", "endoribonuclease rnase 1", "rnase 1 cleaves", "1 cleaves trnas", "cleaves trnas at", "trnas at the", "at the anticodon", "anticodon loop in", "loop in the", "in the extracellular", "the extracellular space", "space nechooshtan", "nechooshtan et al.", "al. 2020 .
              ", "2020 .
              interferon", ".
              interferon induced", "interferon induced rnases", "induced rnases can", "rnases can also", "can also cleave", "also cleave trnas.", "cleave trnas. rnase", "trnas. rnase l", "rnase l is", "l is responsive", "is responsive to", "responsive to double", "to double stranded", "double stranded rnas", "stranded rnas and", "rnas and cleaves", "and cleaves at", "cleaves at the", "at the trna", "the trna anticodon", "trna anticodon loop", "loop donovan", "donovan et al.", "et al. 2017", "al. 2017 .", "2017 . schlafen", ". schlafen family", "schlafen family members", "family members slfn11", "members slfn11 and", "slfn11 and slfn13", "and slfn13 can", "slfn13 can also", "also cleave trnas", "trnas li", "li et al.", "et al. 2018", "2018 yang", "yang et al.", "al. 2018 .
              dicer1", "2018 .
              dicer1 cleaves", ".
              dicer1 cleaves double\u2011stranded", "cleaves double\u2011stranded regions", "double\u2011stranded regions of", "regions of trnas", "of trnas near", "trnas near the", "near the 5'", "the 5' terminus", "5' terminus or", "terminus or 3'", "or 3' terminus", "3' terminus to", "terminus to produce", "to produce short", "produce short trfs", "trfs cole", "cole et al.", "2009 yeung", "yeung et al.", "2009 maute", "maute et al.", "et al. 2013", "2013 hasler", "hasler et al.", "al. 2016 .", "2016 . the", ". the mechanism", "the mechanism that", "mechanism that dissociates", "that dissociates the", "dissociates the double\u2011stranded", "the double\u2011stranded products", "double\u2011stranded products of", "products of dicer1", "of dicer1 to", "dicer1 to yield", "to yield single\u2011stranded", "yield single\u2011stranded trfs", "single\u2011stranded trfs may", "trfs may be", "may be the", "be the same", "the same as", "same as that", "as that for", "that for mirnas", "mirnas but", "but this has", "this has not", "has not yet", "not yet been", "yet been demonstrated.", "been demonstrated. furthermore", "furthermore the", "the bulk of", "bulk of the", "of the short", "the short trfs", "short trfs is", "trfs is still", "is still detected", "still detected in", "detected in dicer1", "in dicer1 null", "dicer1 null cells", "cells kumar", "2014 kuscu", "kuscu & kumar", "& kumar et", "suggesting other unknown", "other unknown factors", "unknown factors are", "factors are involved", "are involved in", "involved in their", "in their biogenesis.", "their biogenesis. elac2", "biogenesis. elac2 in", "elac2 in the", "the cytosol cleaves", "cytosol cleaves the", "cleaves the 3'", "trailers of precursors", "of precursors of", "precursors of trna", "of trna ser", "trna ser tga", "tga trna", "trna ser gtc", "gtc and", "and trna asp", "trna asp gtc", "gtc lee", "lee et al.", "al. 2009 .", "2009 . the", ". the trailers", "trailers also", "also called trf", "called trf 1s", "1s then", "then persist in", "persist in the", "cytosol kumar", "et al. 2014", "al. 2014 .", "defined fragments of trnas", "of trnas termed", "trnas termed trna\u2011derived", "termed trna\u2011derived small rnas", "small rnas tsrnas", "have been observed in", "been observed in particular", "observed in particular cell", "in particular cell types", "particular cell types and", "cell types and in", "types and in response", "and in response to", "in response to biological", "response to biological conditions", "to biological conditions such", "biological conditions such as", "conditions such as exposure", "such as exposure to", "as exposure to sex", "exposure to sex hormone", "to sex hormone or", "sex hormone or stresses", "hormone or stresses such", "or stresses such as", "stresses such as hypoxia", "as hypoxia starvation", "starvation oxidative stress", "oxidative stress and", "stress and virus", "virus infection reviewed", "infection reviewed in", "reviewed in keam and", "in keam and hutvagner", "keam and hutvagner 2015", "hutvagner 2015 kumar", "2015 kumar et", "kumar et al. 2016", "al. 2016 oberbauer", "2016 oberbauer and", "oberbauer and schaefer 2018", "schaefer 2018 park", "2018 park et", "park et al. 2020", "al. 2020 su", "2020 su et", "su et al. 2020", "al. 2020 xie", "2020 xie et", "xie et al. 2020", "al. 2020 zhu", "2020 zhu et", "zhu et al. 2020", "et al. 2020 .", "al. 2020 . rather", "2020 . rather than", ". rather than being", "rather than being the", "than being the random", "being the random products", "the random products of", "random products of trna", "products of trna degradation", "trna degradation tsrnas", "degradation tsrnas appear", "tsrnas appear to be", "appear to be the", "to be the specific", "be the specific products", "the specific products of", "specific products of ribonucleases.", "products of ribonucleases. two", "of ribonucleases. two categories", "ribonucleases. two categories of", "two categories of trna\u2011derived", "categories of trna\u2011derived small", "of trna\u2011derived small rnas", "tsrnas have been", "been described: 1", "31\u201140nt tsrnas known", "tsrnas known as trna", "known as trna halves", "as trna halves or", "trna halves or stress\u2011induced", "halves or stress\u2011induced tsrnas", "stress\u2011induced tsrnas tirnas", "tirnas that are", "that are produced by", "are produced by single", "produced by single cleavage", "by single cleavage of", "single cleavage of trnas", "cleavage of trnas within", "of trnas within or", "trnas within or near", "within or near the", "or near the anticodon", "near the anticodon and", "anticodon and 2", "shorter 15\u201130 nt", "15\u201130 nt tsrnas", "nt tsrnas termed", "tsrnas termed trna related", "termed trna related fragments", "related fragments trfs", "trfs that result", "that result from cleavage", "result from cleavage closer", "from cleavage closer to", "cleavage closer to the", "closer to the 5'", "to the 5' or", "the 5' or 3'", "5' or 3' end", "or 3' end of", "3' end of the", "end of the trna.", "of the trna. trf", "the trna. trf 3s", "trna. trf 3s are", "trf 3s are derived", "3s are derived from", "are derived from the", "derived from the 3'", "from the 3' region", "the 3' region of", "3' region of the", "region of the trna", "the trna approximately", "trna approximately the", "approximately the region from", "the region from the", "region from the t", "from the t loop", "the t loop to", "t loop to the", "loop to the 3'", "to the 3' terminus.", "the 3' terminus. trf", "3' terminus. trf 5s", "terminus. trf 5s are", "trf 5s are derived", "5s are derived from", "derived from the 5'", "from the 5' region", "the 5' region of", "5' region of the", "region from the d", "from the d loop", "the d loop to", "d loop to the", "loop to the 5'", "to the 5' terminus.", "the 5' terminus. trf2\u2011type", "5' terminus. trf2\u2011type trfs", "trf2\u2011type trfs also", "trfs also called", "also called internal trfs", "internal trfs are", "trfs are derived", "derived from the central", "from the central region", "the central region of", "central region of the", "approximately the region between", "the region between the", "region between the d", "between the d loop", "the d loop and", "d loop and the", "loop and the t", "and the t loop", "the t loop and", "t loop and containing", "loop and containing the", "and containing the anticodon.", "containing the anticodon. trf", "the anticodon. trf 1s", "trf 1s also", "1s also known", "also known as type", "known as type ii", "as type ii trfs", "type ii trfs or", "ii trfs or 3\u2019u", "trfs or 3\u2019u trfs", "3\u2019u trfs are", "trfs are the", "are the 3' trailers", "the 3' trailers of", "3' trailers of particular", "trailers of particular trnas", "of particular trnas that", "particular trnas that persist", "trnas that persist after", "that persist after processing.
              in", "persist after processing.
              in most", "after processing.
              in most cases", "processing.
              in most cases the", "most cases the enzymes", "cases the enzymes responsible", "the enzymes responsible for", "enzymes responsible for the", "responsible for the cleavages", "for the cleavages are", "the cleavages are not", "cleavages are not yet", "are not yet known", "yet known however", "known however several", "however several ribonucleases involved", "several ribonucleases involved in", "ribonucleases involved in cleavage", "involved in cleavage of", "in cleavage of trna", "cleavage of trna have", "of trna have been", "trna have been identified:", "have been identified: the", "been identified: the secreted", "identified: the secreted and", "the secreted and endocytosed", "secreted and endocytosed ribonuclease", "and endocytosed ribonuclease a", "endocytosed ribonuclease a family", "ribonuclease a family members", "a family members angiogenin", "members angiogenin ang", "ang and rnase", "rnase 1 the", "1 the interferon", "the interferon induced ribonucleases", "interferon induced ribonucleases rnase", "induced ribonucleases rnase l", "rnase l schlafen", "l schlafen 11", "schlafen 11 slfn11", "slfn11 and schlafen13", "and schlafen13 slfn13", "schlafen13 slfn13 or", "slfn13 or rnase s13", "s13 the", "the cytosolic ribonuclease iii\u2011like", "ribonuclease iii\u2011like double", "iii\u2011like double strand", "strand rna\u2011specific enzyme", "rna\u2011specific enzyme dicer1", "enzyme dicer1 and", "dicer1 and the", "and the rna processing", "the rna processing enzyme", "rna processing enzyme elac2.", "processing enzyme elac2. ang", "enzyme elac2. ang is", "elac2. ang is secreted", "is secreted binds", "secreted binds receptors", "binds receptors on cell", "receptors on cell membranes", "cell membranes is", "membranes is endocytosed", "is endocytosed and", "endocytosed and translocates", "and translocates to the", "translocates to the nucleus.", "to the nucleus. ang", "the nucleus. ang cleaves", "nucleus. ang cleaves within", "ang cleaves within the", "cleaves within the anticodon", "within the anticodon loop", "the anticodon loop to", "anticodon loop to produce", "loop to produce trna", "to produce trna halves", "produce trna halves and", "trna halves and the", "halves and the cleavage", "and the cleavage is", "the cleavage is thought", "cleavage is thought to", "is thought to occur", "thought to occur while", "to occur while ang", "occur while ang is", "while ang is transiently", "ang is transiently located", "is transiently located in", "transiently located in the", "located in the cytosol", "the cytosol lee", "cytosol lee and", "lee and vallee 1989", "vallee 1989 saxena", "1989 saxena et", "saxena et al. 1992", "al. 1992 fu", "1992 fu et", "fu et al. 2009", "al. 2009 yamasaki", "2009 yamasaki et", "yamasaki et al. 2009", "al. 2009 emara", "2009 emara et", "emara et al. 2010", "al. 2010 ivanov", "2010 ivanov et", "ivanov et al. 2011", "et al. 2011 .", "al. 2011 . cleavage", "2011 . cleavage by", ". cleavage by ang", "cleavage by ang is", "by ang is observed", "ang is observed in", "is observed in response", "observed in response to", "in response to cellular", "response to cellular stresses", "to cellular stresses such", "cellular stresses such as", "stresses such as starvation", "as starvation fu", "starvation fu et", "al. 2011 . however", ". however ang", "however ang knockout", "ang knockout cells continue", "knockout cells continue to", "cells continue to produce", "continue to produce stress", "to produce stress induced", "produce stress induced trna", "stress induced trna halves", "trna halves suggesting", "halves suggesting that", "suggesting that other enzymes", "that other enzymes are", "other enzymes are also", "enzymes are also involved", "are also involved in", "also involved in producing", "involved in producing the", "in producing the halves", "the halves su", "halves su et", "su et al. 2019", "et al. 2019 .", "2019 . similar", ". similar to", "similar to ang as", "to ang as an", "ang as an rnase", "as an rnase a", "an rnase a member", "a member the", "member the secreted", "the secreted endoribonuclease rnase", "secreted endoribonuclease rnase 1", "endoribonuclease rnase 1 cleaves", "rnase 1 cleaves trnas", "1 cleaves trnas at", "cleaves trnas at the", "trnas at the anticodon", "at the anticodon loop", "the anticodon loop in", "anticodon loop in the", "loop in the extracellular", "in the extracellular space", "extracellular space nechooshtan", "space nechooshtan et", "nechooshtan et al. 2020", "et al. 2020 .
              ", "al. 2020 .
              interferon", "2020 .
              interferon induced", ".
              interferon induced rnases", "interferon induced rnases can", "induced rnases can also", "rnases can also cleave", "can also cleave trnas.", "also cleave trnas. rnase", "cleave trnas. rnase l", "trnas. rnase l is", "rnase l is responsive", "l is responsive to", "is responsive to double", "responsive to double stranded", "to double stranded rnas", "double stranded rnas and", "stranded rnas and cleaves", "rnas and cleaves at", "and cleaves at the", "cleaves at the trna", "at the trna anticodon", "the trna anticodon loop", "anticodon loop donovan", "loop donovan et", "donovan et al. 2017", "et al. 2017 .", "al. 2017 . schlafen", "2017 . schlafen family", ". schlafen family members", "schlafen family members slfn11", "family members slfn11 and", "members slfn11 and slfn13", "slfn11 and slfn13 can", "and slfn13 can also", "slfn13 can also cleave", "can also cleave trnas", "cleave trnas li", "trnas li et", "li et al. 2018", "al. 2018 yang", "2018 yang et", "yang et al. 2018", "et al. 2018 .
              dicer1", "al. 2018 .
              dicer1 cleaves", "2018 .
              dicer1 cleaves double\u2011stranded", ".
              dicer1 cleaves double\u2011stranded regions", "cleaves double\u2011stranded regions of", "double\u2011stranded regions of trnas", "regions of trnas near", "of trnas near the", "trnas near the 5'", "near the 5' terminus", "the 5' terminus or", "5' terminus or 3'", "terminus or 3' terminus", "or 3' terminus to", "3' terminus to produce", "terminus to produce short", "to produce short trfs", "short trfs cole", "trfs cole et", "cole et al. 2009", "al. 2009 yeung", "2009 yeung et", "yeung et al. 2009", "al. 2009 maute", "2009 maute et", "maute et al. 2013", "al. 2013 hasler", "2013 hasler et", "hasler et al. 2016", "et al. 2016 .", "al. 2016 . the", "2016 . the mechanism", ". the mechanism that", "the mechanism that dissociates", "mechanism that dissociates the", "that dissociates the double\u2011stranded", "dissociates the double\u2011stranded products", "the double\u2011stranded products of", "double\u2011stranded products of dicer1", "products of dicer1 to", "of dicer1 to yield", "dicer1 to yield single\u2011stranded", "to yield single\u2011stranded trfs", "yield single\u2011stranded trfs may", "single\u2011stranded trfs may be", "trfs may be the", "may be the same", "be the same as", "the same as that", "same as that for", "as that for mirnas", "for mirnas but", "mirnas but this", "but this has not", "this has not yet", "has not yet been", "not yet been demonstrated.", "yet been demonstrated. furthermore", "demonstrated. furthermore the", "furthermore the bulk", "the bulk of the", "bulk of the short", "of the short trfs", "the short trfs is", "short trfs is still", "trfs is still detected", "is still detected in", "still detected in dicer1", "detected in dicer1 null", "in dicer1 null cells", "null cells kumar", "cells kumar 2014", "kumar 2014 kuscu", "2014 kuscu &", "kuscu & kumar et", "& kumar et al.", "kumar et al. 2018", "2018 suggesting", "suggesting other unknown factors", "other unknown factors are", "unknown factors are involved", "factors are involved in", "are involved in their", "involved in their biogenesis.", "in their biogenesis. elac2", "their biogenesis. elac2 in", "biogenesis. elac2 in the", "elac2 in the cytosol", "in the cytosol cleaves", "the cytosol cleaves the", "cytosol cleaves the 3'", "cleaves the 3' trailers", "3' trailers of precursors", "trailers of precursors of", "of precursors of trna", "precursors of trna ser", "of trna ser tga", "ser tga trna", "tga trna ser", "ser gtc and", "gtc and trna", "and trna asp gtc", "asp gtc and", "asp gtc lee", "gtc lee et", "lee et al. 2009", "et al. 2009 .", "al. 2009 . the", "2009 . the trailers", "the trailers also", "trailers also called", "also called trf 1s", "trf 1s then", "1s then persist", "then persist in the", "persist in the cytosol", "the cytosol kumar", "cytosol kumar et", "kumar et al. 2014", "et al. 2014 .", "fragments of trnas termed", "of trnas termed trna\u2011derived", "trnas termed trna\u2011derived small", "trna\u2011derived small rnas tsrnas", "have been observed in particular", "been observed in particular cell", "observed in particular cell types", "in particular cell types and", "particular cell types and in", "cell types and in response", "types and in response to", "and in response to biological", "in response to biological conditions", "response to biological conditions such", "to biological conditions such as", "biological conditions such as exposure", "conditions such as exposure to", "such as exposure to sex", "as exposure to sex hormone", "exposure to sex hormone or", "to sex hormone or stresses", "sex hormone or stresses such", "hormone or stresses such as", "or stresses such as hypoxia", "such as hypoxia starvation", "hypoxia starvation oxidative", "oxidative stress and virus", "stress and virus infection", "and virus infection reviewed", "virus infection reviewed in", "infection reviewed in keam", "reviewed in keam and hutvagner", "in keam and hutvagner 2015", "and hutvagner 2015 kumar", "hutvagner 2015 kumar et", "2015 kumar et al.", "et al. 2016 oberbauer", "al. 2016 oberbauer and", "2016 oberbauer and schaefer", "and schaefer 2018 park", "schaefer 2018 park et", "2018 park et al.", "et al. 2020 su", "al. 2020 su et", "2020 su et al.", "et al. 2020 xie", "al. 2020 xie et", "2020 xie et al.", "et al. 2020 zhu", "al. 2020 zhu et", "2020 zhu et al.", "zhu et al. 2020 .", "et al. 2020 . rather", "al. 2020 . rather than", "2020 . rather than being", ". rather than being the", "rather than being the random", "than being the random products", "being the random products of", "the random products of trna", "random products of trna degradation", "of trna degradation tsrnas", "trna degradation tsrnas appear", "degradation tsrnas appear to", "tsrnas appear to be the", "appear to be the specific", "to be the specific products", "be the specific products of", "the specific products of ribonucleases.", "specific products of ribonucleases. two", "products of ribonucleases. two categories", "of ribonucleases. two categories of", "ribonucleases. two categories of trna\u2011derived", "two categories of trna\u2011derived small", "categories of trna\u2011derived small rnas", "rnas tsrnas have", "tsrnas have been described:", "have been described: 1", "described: 1 longer", "1 longer 31\u201140nt", "longer 31\u201140nt tsrnas", "31\u201140nt tsrnas known as", "tsrnas known as trna halves", "known as trna halves or", "as trna halves or stress\u2011induced", "trna halves or stress\u2011induced tsrnas", "or stress\u2011induced tsrnas tirnas", "tsrnas tirnas that", "tirnas that are produced", "that are produced by single", "are produced by single cleavage", "produced by single cleavage of", "by single cleavage of trnas", "single cleavage of trnas within", "cleavage of trnas within or", "of trnas within or near", "trnas within or near the", "within or near the anticodon", "or near the anticodon and", "the anticodon and 2", "and 2 shorter", "2 shorter 15\u201130", "15\u201130 nt tsrnas termed", "nt tsrnas termed trna", "tsrnas termed trna related fragments", "trna related fragments trfs", "fragments trfs that", "trfs that result from", "that result from cleavage closer", "result from cleavage closer to", "from cleavage closer to the", "cleavage closer to the 5'", "closer to the 5' or", "to the 5' or 3'", "the 5' or 3' end", "5' or 3' end of", "or 3' end of the", "3' end of the trna.", "end of the trna. trf", "of the trna. trf 3s", "the trna. trf 3s are", "trna. trf 3s are derived", "trf 3s are derived from", "3s are derived from the", "are derived from the 3'", "derived from the 3' region", "from the 3' region of", "the 3' region of the", "3' region of the trna", "of the trna approximately", "the trna approximately the", "trna approximately the region", "approximately the region from the", "the region from the t", "region from the t loop", "from the t loop to", "the t loop to the", "t loop to the 3'", "loop to the 3' terminus.", "to the 3' terminus. trf", "the 3' terminus. trf 5s", "3' terminus. trf 5s are", "terminus. trf 5s are derived", "trf 5s are derived from", "5s are derived from the", "are derived from the 5'", "derived from the 5' region", "from the 5' region of", "the 5' region of the", "5' region of the trna", "the region from the d", "region from the d loop", "from the d loop to", "the d loop to the", "d loop to the 5'", "loop to the 5' terminus.", "to the 5' terminus. trf2\u2011type", "the 5' terminus. trf2\u2011type trfs", "terminus. trf2\u2011type trfs also", "trf2\u2011type trfs also called", "trfs also called internal", "called internal trfs are", "internal trfs are derived", "trfs are derived from", "are derived from the central", "derived from the central region", "from the central region of", "the central region of the", "central region of the trna", "approximately the region between the", "the region between the d", "region between the d loop", "between the d loop and", "the d loop and the", "d loop and the t", "loop and the t loop", "and the t loop and", "the t loop and containing", "t loop and containing the", "loop and containing the anticodon.", "and containing the anticodon. trf", "containing the anticodon. trf 1s", "anticodon. trf 1s also", "trf 1s also known", "1s also known as", "also known as type ii", "known as type ii trfs", "as type ii trfs or", "type ii trfs or 3\u2019u", "ii trfs or 3\u2019u trfs", "or 3\u2019u trfs are", "3\u2019u trfs are the", "trfs are the 3'", "are the 3' trailers of", "the 3' trailers of particular", "3' trailers of particular trnas", "trailers of particular trnas that", "of particular trnas that persist", "particular trnas that persist after", "trnas that persist after processing.
              in", "that persist after processing.
              in most", "persist after processing.
              in most cases", "after processing.
              in most cases the", "processing.
              in most cases the enzymes", "most cases the enzymes responsible", "cases the enzymes responsible for", "the enzymes responsible for the", "enzymes responsible for the cleavages", "responsible for the cleavages are", "for the cleavages are not", "the cleavages are not yet", "cleavages are not yet known", "not yet known however", "yet known however several", "known however several ribonucleases", "however several ribonucleases involved in", "several ribonucleases involved in cleavage", "ribonucleases involved in cleavage of", "involved in cleavage of trna", "in cleavage of trna have", "cleavage of trna have been", "of trna have been identified:", "trna have been identified: the", "have been identified: the secreted", "been identified: the secreted and", "identified: the secreted and endocytosed", "the secreted and endocytosed ribonuclease", "secreted and endocytosed ribonuclease a", "and endocytosed ribonuclease a family", "endocytosed ribonuclease a family members", "ribonuclease a family members angiogenin", "family members angiogenin ang", "angiogenin ang and", "ang and rnase 1", "and rnase 1 the", "rnase 1 the interferon", "1 the interferon induced", "the interferon induced ribonucleases rnase", "interferon induced ribonucleases rnase l", "ribonucleases rnase l schlafen", "rnase l schlafen 11", "11 slfn11 and", "and schlafen13 slfn13 or", "schlafen13 slfn13 or rnase", "rnase s13 the", "s13 the cytosolic", "cytosolic ribonuclease iii\u2011like double", "ribonuclease iii\u2011like double strand", "iii\u2011like double strand rna\u2011specific", "double strand rna\u2011specific enzyme", "strand rna\u2011specific enzyme dicer1", "enzyme dicer1 and the", "dicer1 and the rna", "and the rna processing enzyme", "the rna processing enzyme elac2.", "rna processing enzyme elac2. ang", "processing enzyme elac2. ang is", "enzyme elac2. ang is secreted", "ang is secreted binds", "is secreted binds receptors", "secreted binds receptors on", "binds receptors on cell membranes", "on cell membranes is", "cell membranes is endocytosed", "is endocytosed and translocates", "endocytosed and translocates to", "and translocates to the nucleus.", "translocates to the nucleus. ang", "to the nucleus. ang cleaves", "the nucleus. ang cleaves within", "nucleus. ang cleaves within the", "ang cleaves within the anticodon", "cleaves within the anticodon loop", "within the anticodon loop to", "the anticodon loop to produce", "anticodon loop to produce trna", "loop to produce trna halves", "to produce trna halves and", "produce trna halves and the", "trna halves and the cleavage", "halves and the cleavage is", "and the cleavage is thought", "the cleavage is thought to", "cleavage is thought to occur", "is thought to occur while", "thought to occur while ang", "to occur while ang is", "occur while ang is transiently", "while ang is transiently located", "ang is transiently located in", "is transiently located in the", "transiently located in the cytosol", "in the cytosol lee", "the cytosol lee and", "cytosol lee and vallee", "and vallee 1989 saxena", "vallee 1989 saxena et", "1989 saxena et al.", "et al. 1992 fu", "al. 1992 fu et", "1992 fu et al.", "et al. 2009 yamasaki", "al. 2009 yamasaki et", "2009 yamasaki et al.", "et al. 2009 emara", "al. 2009 emara et", "2009 emara et al.", "et al. 2010 ivanov", "al. 2010 ivanov et", "2010 ivanov et al.", "ivanov et al. 2011 .", "et al. 2011 . cleavage", "al. 2011 . cleavage by", "2011 . cleavage by ang", ". cleavage by ang is", "cleavage by ang is observed", "by ang is observed in", "ang is observed in response", "is observed in response to", "observed in response to cellular", "in response to cellular stresses", "response to cellular stresses such", "to cellular stresses such as", "cellular stresses such as starvation", "such as starvation fu", "as starvation fu et", "starvation fu et al.", "et al. 2011 . however", "2011 . however ang", ". however ang knockout", "however ang knockout cells", "ang knockout cells continue to", "knockout cells continue to produce", "cells continue to produce stress", "continue to produce stress induced", "to produce stress induced trna", "produce stress induced trna halves", "induced trna halves suggesting", "trna halves suggesting that", "halves suggesting that other", "suggesting that other enzymes are", "that other enzymes are also", "other enzymes are also involved", "enzymes are also involved in", "are also involved in producing", "also involved in producing the", "involved in producing the halves", "producing the halves su", "the halves su et", "halves su et al.", "su et al. 2019 .", "al. 2019 . similar", "2019 . similar to", ". similar to ang", "similar to ang as an", "to ang as an rnase", "ang as an rnase a", "as an rnase a member", "rnase a member the", "a member the secreted", "member the secreted endoribonuclease", "the secreted endoribonuclease rnase 1", "secreted endoribonuclease rnase 1 cleaves", "endoribonuclease rnase 1 cleaves trnas", "rnase 1 cleaves trnas at", "1 cleaves trnas at the", "cleaves trnas at the anticodon", "trnas at the anticodon loop", "at the anticodon loop in", "the anticodon loop in the", "anticodon loop in the extracellular", "loop in the extracellular space", "the extracellular space nechooshtan", "extracellular space nechooshtan et", "space nechooshtan et al.", "nechooshtan et al. 2020 .
              ", "et al. 2020 .
              interferon", "al. 2020 .
              interferon induced", "2020 .
              interferon induced rnases", ".
              interferon induced rnases can", "interferon induced rnases can also", "induced rnases can also cleave", "rnases can also cleave trnas.", "can also cleave trnas. rnase", "also cleave trnas. rnase l", "cleave trnas. rnase l is", "trnas. rnase l is responsive", "rnase l is responsive to", "l is responsive to double", "is responsive to double stranded", "responsive to double stranded rnas", "to double stranded rnas and", "double stranded rnas and cleaves", "stranded rnas and cleaves at", "rnas and cleaves at the", "and cleaves at the trna", "cleaves at the trna anticodon", "at the trna anticodon loop", "trna anticodon loop donovan", "anticodon loop donovan et", "loop donovan et al.", "donovan et al. 2017 .", "et al. 2017 . schlafen", "al. 2017 . schlafen family", "2017 . schlafen family members", ". schlafen family members slfn11", "schlafen family members slfn11 and", "family members slfn11 and slfn13", "members slfn11 and slfn13 can", "slfn11 and slfn13 can also", "and slfn13 can also cleave", "slfn13 can also cleave trnas", "also cleave trnas li", "cleave trnas li et", "trnas li et al.", "et al. 2018 yang", "al. 2018 yang et", "2018 yang et al.", "yang et al. 2018 .
              dicer1", "et al. 2018 .
              dicer1 cleaves", "al. 2018 .
              dicer1 cleaves double\u2011stranded", "2018 .
              dicer1 cleaves double\u2011stranded regions", ".
              dicer1 cleaves double\u2011stranded regions of", "cleaves double\u2011stranded regions of trnas", "double\u2011stranded regions of trnas near", "regions of trnas near the", "of trnas near the 5'", "trnas near the 5' terminus", "near the 5' terminus or", "the 5' terminus or 3'", "5' terminus or 3' terminus", "terminus or 3' terminus to", "or 3' terminus to produce", "3' terminus to produce short", "terminus to produce short trfs", "produce short trfs cole", "short trfs cole et", "trfs cole et al.", "et al. 2009 yeung", "al. 2009 yeung et", "2009 yeung et al.", "et al. 2009 maute", "al. 2009 maute et", "2009 maute et al.", "et al. 2013 hasler", "al. 2013 hasler et", "2013 hasler et al.", "hasler et al. 2016 .", "et al. 2016 . the", "al. 2016 . the mechanism", "2016 . the mechanism that", ". the mechanism that dissociates", "the mechanism that dissociates the", "mechanism that dissociates the double\u2011stranded", "that dissociates the double\u2011stranded products", "dissociates the double\u2011stranded products of", "the double\u2011stranded products of dicer1", "double\u2011stranded products of dicer1 to", "products of dicer1 to yield", "of dicer1 to yield single\u2011stranded", "dicer1 to yield single\u2011stranded trfs", "to yield single\u2011stranded trfs may", "yield single\u2011stranded trfs may be", "single\u2011stranded trfs may be the", "trfs may be the same", "may be the same as", "be the same as that", "the same as that for", "same as that for mirnas", "that for mirnas but", "for mirnas but this", "mirnas but this has", "but this has not yet", "this has not yet been", "has not yet been demonstrated.", "not yet been demonstrated. furthermore", "been demonstrated. furthermore the", "demonstrated. furthermore the bulk", "furthermore the bulk of", "the bulk of the short", "bulk of the short trfs", "of the short trfs is", "the short trfs is still", "short trfs is still detected", "trfs is still detected in", "is still detected in dicer1", "still detected in dicer1 null", "detected in dicer1 null cells", "dicer1 null cells kumar", "null cells kumar 2014", "kumar 2014 kuscu &", "2014 kuscu & kumar", "kuscu & kumar et al.", "& kumar et al. 2018", "al. 2018 suggesting", "2018 suggesting other", "suggesting other unknown factors are", "other unknown factors are involved", "unknown factors are involved in", "factors are involved in their", "are involved in their biogenesis.", "involved in their biogenesis. elac2", "in their biogenesis. elac2 in", "their biogenesis. elac2 in the", "biogenesis. elac2 in the cytosol", "elac2 in the cytosol cleaves", "in the cytosol cleaves the", "the cytosol cleaves the 3'", "cytosol cleaves the 3' trailers", "cleaves the 3' trailers of", "the 3' trailers of precursors", "3' trailers of precursors of", "trailers of precursors of trna", "of precursors of trna ser", "precursors of trna ser tga", "trna ser tga trna", "ser tga trna ser", "tga trna ser gtc", "trna ser gtc and", "ser gtc and trna", "gtc and trna asp", "trna asp gtc and", "asp gtc and trna", "trna asp gtc lee", "asp gtc lee et", "gtc lee et al.", "lee et al. 2009 .", "et al. 2009 . the", "al. 2009 . the trailers", ". the trailers also", "the trailers also called", "trailers also called trf", "called trf 1s then", "trf 1s then persist", "1s then persist in", "then persist in the cytosol", "in the cytosol kumar", "the cytosol kumar et", "cytosol kumar et al.", "kumar et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1845", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9723905", "r hsa", "hsa 9723905", "r hsa 9723905" ] }, { "record_id": "GLY_000594_1_1845", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "loss of", "of function", "function of", "of tp53", "tp53 in", "in cancer", "cancer due", "due to", "to loss", "of tetramerization", "tetramerization ability", "loss of function", "of function of", "function of tp53", "of tp53 in", "tp53 in cancer", "in cancer due", "cancer due to", "due to loss", "to loss of", "loss of tetramerization", "of tetramerization ability", "loss of function of", "of function of tp53", "function of tp53 in", "of tp53 in cancer", "tp53 in cancer due", "in cancer due to", "cancer due to loss", "due to loss of", "to loss of tetramerization", "loss of tetramerization ability", "loss of function of tp53", "of function of tp53 in", "function of tp53 in cancer", "of tp53 in cancer due", "tp53 in cancer due to", "in cancer due to loss", "cancer due to loss of", "due to loss of tetramerization", "to loss of tetramerization ability", "the physiologically", "physiologically active", "active form", "form of", "tp53 is", "is homotetramer", "which represents", "represents a", "a dimer", "dimer of", "of dimers", "lee et", "et al.", "al. 1994", "clore et", "jeffrey et", "al. 1995", "with the", "the dimer", "dimer considered", "considered to", "to represent", "represent a", "a transient", "transient intermediate", "mateau et", "al. 1998", "al. 1999", "natan et", "al. 2009", "2009 .", ". the", "the tetramerization", "tetramerization domain", "tp53 localizes", "localizes to", "to the", "the c", "c terminal", "terminal region", "region and", "and involves", "involves amino", "amino acid", "acid residues", "residues 325", "325 355", "355 and", "and is", "is connected", "connected to", "the dna", "dna binding", "binding domain", "via a", "a short", "short unstructured", "unstructured region", "reviewed in", "in wang", "wang et", "et al", "al 1993", "1993 .", "the destabilizing", "destabilizing effects", "effects of", "of some", "some of", "of the", "the dbd", "dbd mutations", "mutations in", "in tp53", "tp53 can", "can only", "only be", "be observed", "observed in", "in the", "the context", "context of", "the tp53", "tp53 tetramer", "but not", "not in", "in monomeric", "monomeric tp53", "lubin et", "al. 2010", "2010 .", ". a", "a number", "number of", "of nonsense", "nonsense and", "and frameshift", "frameshift truncations", "truncations result", "result in", "in mutant", "mutant tp53", "tp53 proteins", "proteins that", "that lack", "lack the", "tetramerization domain.", "domain. in", "in addition", "several missense", "missense mutations", "mutations affect", "affect the", "of which", "like r342p", "r342p and", "and l344p", "have been", "been shown", "shown to", "to impede", "impede tetramerization", "ch\u00e8ne and", "and bechter", "bechter 1999", ". oligomerization", "oligomerization defective", "defective tp53", "tp53 td", "td mutants", "mutants are", "are considered", "to be", "be complete", "complete loss", "function mutants", "mutants in", "in terms", "terms of", "of their", "their transcriptional", "transcriptional activity", "without altered", "altered specificity", "dominant negative", "negative or", "or gain", "gain of", "function effects", "in ch\u00e8ne", "ch\u00e8ne 2001", "2001 .", ". however", "when overexpressed", "some missense", "missense td", "mutants of", "can form", "form homotetramers", "homotetramers and", "and heterotetramers", "heterotetramers with", "the wild", "wild type", "type tp53", "tp53 which", "which are", "are partially", "partially functional", "functional and", "and some", "some extent", "extent of", "of as", "dn and", "and gof", "gof effects", "effects may", "may not", "not be", "be excluded", "excluded for", "for those", "those mutants", "atz et", "al. 2000", ". in", "the synthetic", "synthetic mutant", "mutant p153", "p153 1", "1 320", "which consists", "consists of", "the first", "first 320", "320 amino", "amino acids", "acids and", "and lacks", "lacks the", "the td", "td and", "and the", "terminal domain", "while unable", "unable to", "to tetramerize", "form stacked", "stacked oligomers", "oligomers at", "at the", "the recombinant", "recombinant target", "target gene", "gene promoter", "promoter and", "and induce", "induce transcription", "transcription at", "at a", "a low", "low level.", "level. stacked", "oligomers are", "are formed", "formed through", "through interactions", "interactions that", "that involve", "involve amino", "residues outside", "outside the", "are facilitated", "facilitated by", "by the", "the presence", "presence of", "of a", "a target", "target dna", "dna sequence", "stenger et", "1994 .", ". recombinant", "recombinant tp53", "tp53 that", "that consists", "of amino", "residues 83", "83 323", "323 also", "also predominantly", "predominantly exists", "exists as", "as a", "a monomer", "the physiologically active", "physiologically active form", "active form of", "form of tp53", "of tp53 is", "tp53 is homotetramer", "homotetramer which", "which represents a", "represents a dimer", "a dimer of", "dimer of dimers", "dimers lee", "lee et al.", "et al. 1994", "1994 clore", "clore et al.", "1994 jeffrey", "jeffrey et al.", "et al. 1995", "with the dimer", "the dimer considered", "dimer considered to", "considered to represent", "to represent a", 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              flt3 internal", ".

              flt3 internal tandem", "internal tandem duplications", "duplications itds", "are found in", "found in ~25", "in ~25 30%", "~25 30% of", "30% of acute", "of acute myeloid", "acute myeloid leukemias", "leukemias and", "and are present", "are present at", "present at lower", "at lower frequencies", "lower frequencies in", "frequencies in other", "in other cancers", "cancers reviewed", "reviewed in kazi", "in kazi and", "kazi and roostrand", "roostrand 2019", "2019 patnaik", "patnaik et al", "2018 . these", ". these itds", "these itds generally", "itds generally occur", "generally occur in", "occur in a", "in a tyrosine", "a tyrosine rich", "tyrosine rich region", "rich region of", "region of exon", "of exon 14", "14 encoding", "encoding the juxtamembrane", "the juxtamembrane domain", "juxtamembrane domain region", "domain region of", "region of the", "of the protein", "protein at", "at a lower", "a lower frequency", "frequency itds", "itds are found", "found in the", "in the first", "the first tyrosine", "first tyrosine kinase", "tyrosine kinase domain", "domain tkd1", "tkd1 . in", ". in addition", "in addition to", "addition to itds", "itds a", "a number of", "number of point", "of point mutations", "point mutations in", "mutations in the", "in the juxtamembrane", "juxtamembrane domain have", "domain have also", "have also been", "also been identified.", "been identified. juxtamembrane", "identified. juxtamembrane domain", "juxtamembrane domain mutations", "domain mutations affect", "mutations affect an", "affect an autoinhibitory", "an autoinhibitory loop", "loop shifting", "shifting the equilibrium", "the equilibrium of", "equilibrium of the", "the receptor towards", "receptor towards the", "towards the activated", "the activated state", "state despite", "this however", "however juxtamembrane", "juxtamembrane domain mutants", "domain mutants remain", "mutants remain predominantly", "remain predominantly in", "predominantly in the", "in the inactive", "the inactive state", "inactive state and", "state and as", "and as such", "as such are", "such are susceptible", "are susceptible to", "susceptible to inhibition", "to inhibition by", "inhibition by type", "by type ii", "tkis reviewed", "reviewed in patnaik", "in patnaik et", "2018 kazi", "kazi and roonstrand", "and roonstrand et", "roonstrand et al", "2019 .

              activation", ".

              activation loop", "

              activation loop mutations", "loop mutations more", "mutations more strongly", "more strongly favor", "strongly favor the", "favor the active", "the active conformation", "active conformation of", "conformation of the", "the receptor and", "receptor and are", "and are susceptible", "inhibition by both", "by both type", "both type ii", "type ii and", "ii and type", "and type i", "type i tkis.", "i tkis. the", "tkis. the most", "the most prevalent", "most prevalent flt3", "prevalent flt3 mutation", "mutation d835y", "d835y promotes", "promotes the active", "active conformation strongly", "conformation strongly enough", "strongly enough to", "enough to be", "to be resistant", "be resistant to", "resistant to type", "to type ii", "tkis patnaik", "al 2017", "2017 klug", "aberrant signaling by activated", "signaling by activated forms", "by activated forms of", "activated forms of flt3", "forms of flt3 can", "of flt3 can be", "flt3 can be inhibited", "can be inhibited by", "be inhibited by tyrosine", "inhibited by tyrosine kinase", "by tyrosine kinase inhibitors", "kinase inhibitors tkis", "inhibitors tkis .", "tkis . flt3 receptors", ". flt3 receptors are", "flt3 receptors are class", "receptors are class iii", "are class iii receptor", "class iii receptor tyrosine", "iii receptor tyrosine kinase", "receptor tyrosine kinase receptors", "kinase receptors also", "receptors also known", "also known as dual", "known as dual switch.", "as dual switch. dual", "dual switch. dual switch", "switch. dual switch receptors", "dual switch receptors are", "switch receptors are activated", "receptors are activated through", "are activated through a", "activated through a series", "through a series of", "a series of phosphorylation", "series of phosphorylation and", "of phosphorylation and conformational", "phosphorylation and conformational changes", "and conformational changes that", "conformational changes that move", "changes that move the", "that move the receptor", "move the receptor from", "the receptor from the", "receptor from the inactive", "from the inactive form", "the inactive form to", "inactive form to the", "form to the fully", "to the fully activated", "the fully activated form.", "fully activated form. type", "activated form. type ii", "form. type ii tkis", "type ii tkis bind", "ii tkis bind to", "tkis bind to the", "bind to the inactive", "to the inactive form", "the inactive form of", "inactive form of the", "form of the receptor", "of the receptor at", "the receptor at a", "receptor at a site", "at a site adjacent", "a site adjacent to", "site adjacent to the", "adjacent to the atp", "to the atp binding", "the atp binding cleft", "binding cleft while", "cleft while type", "while type i tkis", "type i tkis bind", "i tkis bind to", "bind to the active", "to the active form", "active form reviewed", "form reviewed in", "reviewed in klug et", "in klug et al", "et al 2018", "2018 daver et", "et al 2019", "al 2019 .

              flt3", "2019 .

              flt3 internal tandem", ".

              flt3 internal tandem duplications", "tandem duplications itds", "are found in ~25", "found in ~25 30%", "in ~25 30% of", "~25 30% of acute", "30% of acute myeloid", "of acute myeloid leukemias", "myeloid leukemias and", "leukemias and are", "and are present at", "are present at lower", "present at lower frequencies", "at lower frequencies in", "lower frequencies in other", "frequencies in other cancers", "other cancers reviewed", "cancers reviewed in", "reviewed in kazi and", "in kazi and roostrand", "and roostrand 2019", "2019 patnaik et", "al 2018 .", "2018 . these itds", ". these itds generally", "these itds generally occur", "itds generally occur in", "generally occur in a", "occur in a tyrosine", "in a tyrosine rich", "a tyrosine rich region", "tyrosine rich region of", "rich region of exon", "region of exon 14", "exon 14 encoding", "14 encoding the", "encoding the juxtamembrane domain", "the juxtamembrane domain region", "juxtamembrane domain region of", "domain region of the", "region of the protein", "the protein at", "protein at a", "at a lower frequency", "lower frequency itds", "frequency itds are", "itds are found in", "are found in the", "found in the first", "in the first tyrosine", "the first tyrosine kinase", "first tyrosine kinase domain", "kinase domain tkd1", "domain tkd1 .", "tkd1 . in addition", ". in addition to", "in addition to itds", "to itds a", "itds a number", "a number of point", "number of point mutations", "of point mutations in", "point mutations in the", "mutations in the juxtamembrane", "in the juxtamembrane domain", "the juxtamembrane domain have", "juxtamembrane domain have also", "domain have also been", "have also been identified.", "also been identified. juxtamembrane", "been identified. juxtamembrane domain", "identified. juxtamembrane domain mutations", "juxtamembrane domain mutations affect", "domain mutations affect an", "mutations affect an autoinhibitory", "affect an autoinhibitory loop", "autoinhibitory loop shifting", "loop shifting the", "shifting the equilibrium of", "the equilibrium of the", "equilibrium of the receptor", "of the receptor towards", "the receptor towards the", "receptor towards the activated", "towards the activated state", "activated state despite", "state despite this", "despite this however", "however juxtamembrane domain", "juxtamembrane domain mutants remain", "domain mutants remain predominantly", "mutants remain predominantly in", "remain predominantly in the", "predominantly in the inactive", "in the inactive state", "the inactive state and", "inactive state and as", "state and as such", "and as such are", "as such are susceptible", "such are susceptible to", "are susceptible to inhibition", "susceptible to inhibition by", "to inhibition by type", "inhibition by type ii", "by type ii tkis", "ii tkis reviewed", "tkis reviewed in", "reviewed in patnaik et", "in patnaik et al", "2018 kazi and", "kazi and roonstrand et", "and roonstrand et al", "al 2019 .", "2019 .

              activation loop", ".

              activation loop mutations", "

              activation loop mutations more", "loop mutations more strongly", "mutations more strongly favor", "more strongly favor the", "strongly favor the active", "favor the active conformation", "the active conformation of", "active conformation of the", "conformation of the receptor", "of the receptor and", "the receptor and are", "receptor and are susceptible", "and are susceptible to", "to inhibition by both", "inhibition by both type", "by both type ii", "both type ii and", "type ii and type", "ii and type i", "and type i tkis.", "type i tkis. the", "i tkis. the most", "tkis. the most prevalent", "the most prevalent flt3", "most prevalent flt3 mutation", "flt3 mutation d835y", "d835y promotes the", "promotes the active conformation", "the active conformation strongly", "active conformation strongly enough", "conformation strongly enough to", "strongly enough to be", "enough to be resistant", "to be resistant to", "be resistant to type", "resistant to type ii", "to type ii tkis", "ii tkis patnaik", "tkis patnaik et", "et al 2017", "2017 klug et", "aberrant signaling by activated forms", "signaling by activated forms of", "by activated forms of flt3", "activated forms of flt3 can", "forms of flt3 can be", "of flt3 can be inhibited", "flt3 can be inhibited by", "can be inhibited by tyrosine", "be inhibited by tyrosine kinase", "inhibited by tyrosine kinase inhibitors", "tyrosine kinase inhibitors tkis", "kinase inhibitors tkis .", "inhibitors tkis . flt3", "tkis . flt3 receptors are", ". flt3 receptors are class", "flt3 receptors are class iii", "receptors are class iii receptor", "are class iii receptor tyrosine", "class iii receptor tyrosine kinase", "iii receptor tyrosine kinase receptors", "tyrosine kinase receptors also", "kinase receptors also known", "receptors also known as", "also known as dual switch.", "known as dual switch. dual", "as dual switch. dual switch", "dual switch. dual switch receptors", "switch. dual switch receptors are", "dual switch receptors are activated", "switch receptors are activated through", "receptors are activated through a", "are activated through a series", "activated through a series of", "through a series of phosphorylation", "a series of phosphorylation and", "series of phosphorylation and conformational", "of phosphorylation and conformational changes", "phosphorylation and conformational changes that", "and conformational changes that move", "conformational changes that move the", "changes that move the receptor", "that move the receptor from", "move the receptor from the", "the receptor from the inactive", "receptor from the inactive form", "from the inactive form to", "the inactive form to the", "inactive form to the fully", "form to the fully activated", "to the fully activated form.", "the fully activated form. type", "fully activated form. type ii", "activated form. type ii tkis", "form. type ii tkis bind", "type ii tkis bind to", "ii tkis bind to the", "tkis bind to the inactive", "bind to the inactive form", "to the inactive form of", "the inactive form of the", "inactive form of the receptor", "form of the receptor at", "of the receptor at a", "the receptor at a site", "receptor at a site adjacent", "at a site adjacent to", "a site adjacent to the", "site adjacent to the atp", "adjacent to the atp binding", "to the atp binding cleft", "atp binding cleft while", "binding cleft while type", "cleft while type i", "while type i tkis bind", "type i tkis bind to", "i tkis bind to the", "tkis bind to the active", "bind to the active form", "the active form reviewed", "active form reviewed in", "form reviewed in klug", "reviewed in klug et al", "klug et al 2018", "al 2018 daver", "2018 daver et al", "daver et al 2019", "et al 2019 .

              flt3", "al 2019 .

              flt3 internal", "2019 .

              flt3 internal tandem duplications", "internal tandem duplications itds", "duplications itds are", "are found in ~25 30%", "found in ~25 30% of", "in ~25 30% of acute", "~25 30% of acute myeloid", "30% of acute myeloid leukemias", "acute myeloid leukemias and", "myeloid leukemias and are", "leukemias and are present", "and are present at lower", "are present at lower frequencies", "present at lower frequencies in", "at lower frequencies in other", "lower frequencies in other cancers", "in other cancers reviewed", "other cancers reviewed in", "cancers reviewed in kazi", "reviewed in kazi and roostrand", "kazi and roostrand 2019", "roostrand 2019 patnaik", "2019 patnaik et al", "patnaik et al 2018", "et al 2018 .", "al 2018 . these", "2018 . these itds generally", ". these itds generally occur", "these itds generally occur in", "itds generally occur in a", "generally occur in a tyrosine", "occur in a tyrosine rich", "in a tyrosine rich region", "a tyrosine rich region of", "tyrosine rich region of exon", "rich region of exon 14", "of exon 14 encoding", "exon 14 encoding the", "14 encoding the juxtamembrane", "encoding the juxtamembrane domain region", "the juxtamembrane domain region of", "juxtamembrane domain region of the", "domain region of the protein", "of the protein at", "the protein at a", "protein at a lower", "a lower frequency itds", "lower frequency itds are", "frequency itds are found", "itds are found in the", "are found in the first", "found in the first tyrosine", "in the first tyrosine kinase", "the first tyrosine kinase domain", "tyrosine kinase domain tkd1", "kinase domain tkd1 .", "domain tkd1 . in", "tkd1 . in addition to", ". in addition to itds", "addition to itds a", "to itds a number", "itds a number of", "a number of point mutations", "number of point mutations in", "of point mutations in the", "point mutations in the juxtamembrane", "mutations in the juxtamembrane domain", "in the juxtamembrane domain have", "the juxtamembrane domain have also", "juxtamembrane domain have also been", "domain have also been identified.", "have also been identified. juxtamembrane", "also been identified. juxtamembrane domain", "been identified. juxtamembrane domain mutations", "identified. juxtamembrane domain mutations affect", "juxtamembrane domain mutations affect an", "domain mutations affect an autoinhibitory", "mutations affect an autoinhibitory loop", "an autoinhibitory loop shifting", "autoinhibitory loop shifting the", "loop shifting the equilibrium", "shifting the equilibrium of the", "the equilibrium of the receptor", "equilibrium of the receptor towards", "of the receptor towards the", "the receptor towards the activated", "receptor towards the activated state", "the activated state despite", "activated state despite this", "this however juxtamembrane", "however juxtamembrane domain mutants", "juxtamembrane domain mutants remain predominantly", "domain mutants remain predominantly in", "mutants remain predominantly in the", "remain predominantly in the inactive", "predominantly in the inactive state", "in the inactive state and", "the inactive state and as", "inactive state and as such", "state and as such are", "and as such are susceptible", "as such are susceptible to", "such are susceptible to inhibition", "are susceptible to inhibition by", "susceptible to inhibition by type", "to inhibition by type ii", "inhibition by type ii tkis", "type ii tkis reviewed", "ii tkis reviewed in", "tkis reviewed in patnaik", "reviewed in patnaik et al", "al 2018 kazi", "2018 kazi and roonstrand", "kazi and roonstrand et al", "roonstrand et al 2019", "et al 2019 .", "al 2019 .

              activation", "2019 .

              activation loop mutations", ".

              activation loop mutations more", "

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enough", "active conformation strongly enough to", "conformation strongly enough to be", "strongly enough to be resistant", "enough to be resistant to", "to be resistant to type", "be resistant to type ii", "resistant to type ii tkis", "type ii tkis patnaik", "ii tkis patnaik et", "tkis patnaik et al", "patnaik et al 2017", "al 2017 klug", "2017 klug et al" ] }, { "record_id": "GLY_000594_1_1852", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9702518", "r hsa", "hsa 9702518", "r hsa 9702518" ] }, { "record_id": "GLY_000594_1_1852", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "stat5 activation", "activation downstream", "downstream of", "of flt3", "flt3 itd", "itd mutants", "stat5 activation downstream", "activation downstream of", "downstream of flt3", "of flt3 itd", "flt3 itd mutants", "stat5 activation downstream of", "activation downstream of flt3", "downstream of flt3 itd", "of flt3 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2021 . organic acids", "2021 . organic acids such", ". organic acids such as", "organic acids such as acetic", "acids such as acetic acid", "such as acetic acid and", "as acetic acid and citric", "acetic acid and citric acid", "acid and citric acid are", "and citric acid are believed", "citric acid are believed to", "acid are believed to also", "are believed to also enter", "believed to also enter type", "to also enter type iii", "also enter type iii taste", "enter type iii taste bud", "iii taste bud cells by", "taste bud cells by passive", "bud cells by passive diffusion", "cells by passive diffusion of", "by passive diffusion of the", "passive diffusion of the protonated", "of the protonated uncharged", "protonated uncharged form", "uncharged form of the", "form of the acid across", "of the acid across the", "the acid across the plasma", "acid across the plasma membrane.", "across the plasma membrane. the", "the plasma membrane. the increase", "plasma membrane. the increase in", 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"fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9730628", "r hsa", "hsa 9730628", "r hsa 9730628" ] }, { "record_id": "GLY_000594_1_1870", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sensory perception", "perception of", "of salty", "salty taste", "sensory perception of", "perception of salty", "of salty taste", "sensory perception of salty", "perception of salty taste", "sensory perception of salty taste", "type i", "i taste", "taste bud", "bud cells", "cells were", "were suggested", "suggested to", "to be", "be responsible", "responsible for", "for tasting", "tasting low", "low concentrations", "concentrations of", "of salt", "however a", "a subset", "subset of", "of type", "type ii", "ii taste", "cells are", "are now", "now thought", "thought to", "nomura et", "et al.", "al. 2020", "2020 .", ". the", "the identity", "identity of", "salt tasting", "tasting cells", "cells remains", "remains a", "a subject", "subject of", "of current", 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              activating mutations", "mutations in", "in fgfr3", "fgfr3 are", "are associated", "associated with", "with the", "the development", "development of", "of a", "a range", "range of", "of skeletal", "skeletal dysplasias", "dysplasias that", "that result", "result in", "in dwarfism", "reviewed in", "in webster", "webster and", "and donoghue", "burke et", "et al", "harada et", "2009 .", "the most", "most common", "common form", "form of", "of human", "human dwarfism", "dwarfism is", "is achondroplasia", "which is", "is caused", "caused by", "by mutations", "mutations g380r", "g380r and", "and g375c", "g375c in", "the transmembrane", "transmembrane domain", "domain of", "of fgfr3", "fgfr3 that", "that are", "are thought", "thought to", "to promote", "promote ligand", "ligand independent", "independent dimerization", "rousseau et", "shiang et", "bellus et", "is a", "a milder", "milder form", "form dwarfism", "dwarfism that", "that is", "is the", "the result", "result of", "of mutations", "the tyrosine", "tyrosine kinase", "kinase domain", "1995b .", "two neonatal", "neonatal lethal", "lethal conditions", "thanatophoric dysplasia", "dysplasia type", "type i", "i and", "and ii", "tdi and", "and tdii", "are also", "also the", "tdi arises", "arises from", "from a", "mutations that", "that either", "either result", "the formation", "formation of", "of unpaired", "unpaired cysteine", "cysteine residues", "residues in", "the extracellular", "extracellular region", "region that", "that promote", "promote aberrant", "aberrant ligand", "dimerization or", "or by", "that introduce", "introduce stop", "stop codons", "d'avis et", "al 1998", "1998 .", "a single", "single mutation", "k650e in", "the second", "second tyrosine", "fgfr3 is", "is responsible", "responsible for", "for all", "all identified", "identified cases", "cases of", "of tdii", "tavormina et", "b .", "other missense", "missense mutations", "mutations at", "at the", "the same", "same k650", "k650 residue", "residue give", "give rise", "rise to", "to severe", "severe achondroplasia", "achondroplasia with", "with developmental", "disorders and", "and acanthosis", "acanthosis nigricans", "1999 .", "the severity", "severity of", "of the", "the phenotype", "phenotype arising", "arising from", "from many", "many of", "the activating", "activating fgfr3", "fgfr3 mutations", "mutations has", "has recently", "recently been", "to correlate", "correlate with", "the extent", "extent to", "to which", "which the", "the mutations", "mutations activate", "activate the", "the receptor", "naski et", "

              in addition", "addition to", "to mutations", "that cause", "cause dwarfism", "dwarfism syndromes", "a pro250arg", "pro250arg mutation", "mutation in", "the conserved", "conserved dipeptide", "dipeptide between", "between the", "the igii", "igii and", "and igiii", "igiii domains", "domains has", "been identified", "identified in", "in an", "an atypical", "atypical craniosynostosis", "craniosynostosis condition", "reardon et", "1997 .", "this mutation", "is paralogous", "paralogous to", "mutations seen", "seen in", "in fgfr1", "fgfr1 and", "and 2", "2 in", "in pfeiffer", "pfeiffer and", "and apert", "apert syndrome", "results in", "an increase", "increase in", "in ligand", "ligand binding", "binding affinity", "affinity for", "for the", "ibrahimi et", "2004b .


              of", ".


              of all", "all the", "the fgf", "fgf receptors", "fgfr3 has", "has perhaps", "perhaps the", "the best", "best established", "established link", "link to", "to the", "development in", "in cancer.", "50% of", "of bladder", "bladder cancers", "cancers have", "have somatic", "somatic mutations", "the coding", "coding sequence", "sequence of", "of these", "more than", "than half", "half occur", "region at", "at a", "single position", "cappellen et", "di martino", "martino et", "sibley et", "2001 .", "mutations are", "also seen", "the juxta", "and trans", "trans membrane", "membrane domains", "as well", "well as", "as in", "the kinase", "in weshe", "weshe et", "2011 .", "as is", "the case", "case for", "the other", "other receptors", "are seen", "fgfr3 related", "related cancers", "cancers mimic", "mimic the", "germline fgfr3", "that give", "to autosomal", "autosomal skeletal", "skeletal disorders", "and include", "include both", "both ligand", "ligand dependent", "dependent and", "and independent", "independent mechanisms", ". in", "in addition", "gene is", "is subject", "a translocation", "translocation event", "event in", "in 15%", "15% of", "of multiple", "multiple myelomas", "avet loiseau", "loiseau et", "chesi et", "this chromosomal", "chromosomal rearrangement", "rearrangement puts", "puts the", "gene under", "under the", "the control", "control of", "the highly", "highly active", "active igh", "igh promoter", "promoter and", "and promotes", "promotes overexpression", "overexpression and", "and constitutive", "constitutive activation", "activation of", "of fgfr3.", "in a", "a small", "small proportion", "proportion of", "the translocation", "event is", "is accompanied", "accompanied by", "by activating", "fgfr3 coding", "1997 .

              more", ".

              more recently", "a number", "number of", "of fusion", "fusion proteins", "proteins of", "fgfr3 have", "have been", "in various", "various cancers", "singh et", "williams et", "parker et", "wu et", "wang et", "yuan et", "in parker", "2014 .", ". the", "common fusion", "fusion protein", "protein is", "is tacc3", "a coiled", "coiled coil", "coil protein", "protein involved", "involved in", "in mitotic", "mitotic spindle", "spindle assembly.", "fgfr3 fusion", "proteins are", "are constitutively", "constitutively active", "active and", "and appear", "appear to", "to contribute", "contribute to", "to proliferation", "proliferation and", "and tumorigenesis", "tumorigenesis through", "through activation", "the erk", "erk and", "and akt", "akt signaling", "signaling pathways", "the fgfr3 gene", "fgfr3 gene has", "gene has been", "has been shown", "been shown to", "shown to be", "to be subject", "be subject to", "subject to activating", "to activating mutations", "activating mutations and", "mutations and gene", "and gene amplification", "gene amplification leading", "amplification leading to", "leading to a", "to a variety", "a variety of", "variety of proliferative", "of proliferative and", "proliferative and developmental", "and developmental disorders", "developmental disorders depending", "disorders depending on", "depending on whether", "on whether these", "whether these events", "these events occur", "events occur in", "occur in the", "in the germline", "the germline or", "germline or arise", "or arise somatically.", "somatically.

              activating", "

              activating mutations in", "mutations in fgfr3", "in fgfr3 are", "fgfr3 are associated", "are associated with", "associated with the", "with the development", "the development of", "development of a", "of a range", "a range of", "range of skeletal", "of skeletal dysplasias", "skeletal dysplasias that", "dysplasias that result", "that result in", "result in dwarfism", "dwarfism reviewed", "reviewed in webster", "in webster and", "webster and donoghue", "donoghue 1997", "1997 burke", "burke et al", "1998 harada", "harada et al", "al 2009", "the most common", "most common form", "common form of", "form of human", "of human dwarfism", "human dwarfism is", "dwarfism is achondroplasia", "achondroplasia ach", "which is caused", "is caused by", "caused by mutations", "by mutations g380r", "mutations g380r and", "g380r and g375c", "and g375c in", "g375c in the", "in the transmembrane", "the transmembrane domain", "transmembrane domain of", "domain of fgfr3", "of fgfr3 that", "fgfr3 that are", "that are thought", "are thought to", "thought to promote", "to promote ligand", "promote ligand independent", "ligand independent dimerization", "dimerization rousseau", "rousseau et al", "al 1994", "1994 shiang", "shiang et al", "1994 bellus", "bellus et al", "al 1995a", "hypochondroplasia hch", "hch is", "is a milder", "a milder form", "milder form dwarfism", "form dwarfism that", "dwarfism that is", "that is the", "is the result", "the result of", "result of mutations", "of mutations in", "mutations in the", "in the tyrosine", "the tyrosine kinase", "tyrosine kinase domain", "kinase domain of", "fgfr3 bellus", "al 1995b", ". two", "two neonatal lethal", "neonatal lethal conditions", "conditions thanatophoric", "thanatophoric dysplasia type", "dysplasia type i", "type i and", "i and ii", "ii tdi", "tdi and tdii", "tdii are", "are also the", "also the result", "fgfr3 tdi", "tdi arises from", "arises from a", "from a range", "range of mutations", "of mutations that", "mutations that either", "that either result", "either result in", "result in the", "in the formation", "the formation of", "formation of unpaired", "of unpaired cysteine", "unpaired cysteine residues", "cysteine residues in", "residues in the", "in the extracellular", "the extracellular region", "extracellular region that", "region that promote", "that promote aberrant", "promote aberrant ligand", "aberrant ligand independent", "independent dimerization or", "dimerization or by", "or by mutations", "by mutations that", "mutations that introduce", "that introduce stop", "introduce stop codons", "codons rousseau", "al 1995", "1995 rousseau", "al 1996", "1996 d'avis", "d'avis et al", "et al 1998", "al 1998 .", ". a", "a single mutation", "mutation k650e", "k650e in the", "in the second", "the second tyrosine", "second tyrosine kinase", "of fgfr3 is", "fgfr3 is responsible", "is responsible for", "responsible for all", "for all identified", "all identified cases", "identified cases of", "cases of tdii", "tdii tavormina", "tavormina et al", "1995a b", ". other", "other missense mutations", "missense mutations at", "mutations at the", "at the same", "the same k650", "same k650 residue", "k650 residue give", "residue give rise", "give rise to", "rise to severe", "to severe achondroplasia", "severe achondroplasia with", "achondroplasia with developmental", "with developmental disorders", "developmental disorders and", "disorders and acanthosis", "and acanthosis nigricans", "nigricans saddan", "saddan syndrome", "syndrome tavormina", "al 1999", "1999 bellus", "the severity of", "severity of the", "of the phenotype", "the phenotype arising", "phenotype arising from", "arising from many", "from many of", "many of the", "of the activating", "the activating fgfr3", "activating fgfr3 mutations", "fgfr3 mutations has", "mutations has recently", "has recently been", "recently been shown", "shown to correlate", "to correlate with", "correlate with the", "with the extent", "the extent to", "extent to which", "to which the", "which the mutations", "the mutations activate", "mutations activate the", "activate the receptor", "receptor naski", "naski et al", "1996 bellus", "al 2000", "2000

              in", "

              in addition to", "addition to mutations", "to mutations that", "mutations that cause", "that cause dwarfism", "cause dwarfism syndromes", "syndromes a", "a pro250arg mutation", "pro250arg mutation in", "mutation in the", "in the conserved", "the conserved dipeptide", "conserved dipeptide between", "dipeptide between the", "between the igii", "the igii and", "igii and igiii", "and igiii domains", "igiii domains has", "domains has been", "has been identified", "been identified in", "identified in an", "in an atypical", "an atypical craniosynostosis", "atypical craniosynostosis condition", "condition bellus", "1996 reardon", "reardon et al", "al 1997", ". this", "mutation which", "which is paralogous", "is paralogous to", "paralogous to mutations", "to mutations seen", "mutations seen in", "seen in fgfr1", "in fgfr1 and", "fgfr1 and 2", "and 2 in", "2 in pfeiffer", "in pfeiffer and", "pfeiffer and apert", "and apert syndrome", "syndrome respectively", "respectively results", "results in an", "in an increase", "an increase in", "increase in ligand", "in ligand binding", "ligand binding affinity", "binding affinity for", "affinity for the", "for the receptor", "receptor ibrahimi", "ibrahimi et al", "al 2004b", "2004b .


              of all", ".


              of all the", "all the fgf", "the fgf receptors", "receptors fgfr3", "fgfr3 has perhaps", "has perhaps the", "perhaps the best", "the best established", "best established link", "established link to", "link to the", "to the development", "the development in", "development in cancer.", "cancer. 50%", "50% of bladder", "of bladder cancers", "bladder cancers have", "cancers have somatic", "have somatic mutations", "somatic mutations in", "in the coding", "the coding sequence", "coding sequence of", "sequence of fgfr3", "fgfr3 of", "these more", "more than half", "than half occur", "half occur in", "extracellular region at", "region at a", "at a single", "a single position", "position s249c", "cappellen et al", "1999 naski", "1996 di", "di martino et", "martino et al", "2009 sibley", "sibley et al", "al 2001", ". activating", "activating mutations are", "mutations are also", "are also seen", "also seen in", "seen in the", "in the juxta", "juxta and", "and trans membrane", "trans membrane domains", "domains as", "as well as", "well as in", "as in the", "in the kinase", "the kinase domain", "domain reviewed", "reviewed in weshe", "in weshe et", "weshe et al", "al 2011", ". as", "as is the", "is the case", "the case for", "case for the", "for the other", "the other receptors", "receptors many", "the activating mutations", "activating mutations that", "mutations that are", "that are seen", "are seen in", "seen in fgfr3", "in fgfr3 related", "fgfr3 related cancers", "related cancers mimic", "cancers mimic the", "mimic the germline", "the germline fgfr3", "germline fgfr3 mutations", "fgfr3 mutations that", "mutations that give", "that give rise", "rise to autosomal", "to autosomal skeletal", "autosomal skeletal disorders", "skeletal disorders and", "disorders and include", "and include both", "include both ligand", "both ligand dependent", "ligand dependent and", "dependent and independent", "and independent mechanisms", "mechanisms reviewed", "1998 . in", ". in addition", "in addition to", "addition to activating", "mutations the", "fgfr3 gene is", "gene is subject", "is subject to", "subject to a", "to a translocation", "a translocation event", "translocation event in", "event in 15%", "in 15% of", "15% of multiple", "of multiple myelomas", "myelomas avet", "avet loiseau et", "loiseau et al", "1998 chesi", "chesi et al", "this chromosomal rearrangement", "chromosomal rearrangement puts", "rearrangement puts the", "puts the fgfr3", "fgfr3 gene under", "gene under the", "under the control", "the control of", "control of the", "of the highly", "the highly active", "highly active igh", "active igh promoter", "igh promoter and", "promoter and promotes", "and promotes overexpression", "promotes overexpression and", "overexpression and constitutive", "and constitutive activation", "constitutive activation of", "activation of fgfr3.", "fgfr3. in", "in a small", "a small proportion", "small proportion of", "proportion of multiple", "myelomas the", "the translocation event", "translocation event is", "event is accompanied", "is accompanied by", "accompanied by activating", "by activating mutations", "activating mutations in", "in the fgfr3", "the fgfr3 coding", "fgfr3 coding sequence", "sequence chesi", "1997 .

              more recently", "recently a", "a number of", "number of fusion", "of fusion proteins", "fusion proteins of", "proteins of fgfr3", "of fgfr3 have", "fgfr3 have been", "have been identified", "identified in various", "in various cancers", "cancers singh", "singh et al", "al 2012", "2012 williams", "williams et al", "al 2013", "2013 parker", "parker et al", "2013 wu", "wu et al", "2013 wang", "wang et al", "al 2014", "2014 yuan", "yuan et al", "2014 reviewed", "reviewed in parker", "in parker et", "2014 . the", ". the most", "most common fusion", "common fusion protein", "fusion protein is", "protein is tacc3", "tacc3 a", "a coiled coil", "coiled coil protein", "coil protein involved", "protein involved in", "involved in mitotic", "in mitotic spindle", "mitotic spindle assembly.", "assembly. fgfr3", "fgfr3 fusion proteins", "fusion proteins are", "proteins are constitutively", "are constitutively active", "constitutively active and", "active and appear", "and appear to", "appear to contribute", "to contribute to", "contribute to proliferation", "to proliferation and", "proliferation and tumorigenesis", "and tumorigenesis through", "tumorigenesis through activation", "through activation of", "activation of the", "of the erk", "the erk and", "erk and akt", "and akt signaling", "akt signaling pathways", "pathways reviewed", "the fgfr3 gene has", "fgfr3 gene has been", "gene has been shown", "has been shown to", "been shown to be", "shown to be subject", "to be subject to", "be subject to activating", "subject to activating mutations", "to activating mutations and", "activating mutations and gene", "mutations and gene amplification", "and gene amplification leading", "gene amplification leading to", "amplification leading to a", "leading to a variety", "to a variety of", "a variety of proliferative", "variety of proliferative and", "of proliferative and developmental", "proliferative and developmental disorders", "and developmental disorders depending", "developmental disorders depending on", "disorders depending on whether", "depending on whether these", "on whether these events", "whether these events occur", "these events occur in", "events occur in the", "occur in the germline", "in the germline or", "the germline or arise", "germline or arise somatically.", "arise somatically.

              activating", "somatically.

              activating mutations", "

              activating mutations in fgfr3", "mutations in fgfr3 are", "in fgfr3 are associated", "fgfr3 are associated with", "are associated with the", "associated with the development", "with the development of", "the development of a", "development of a range", "of a range of", "a range of skeletal", "range of skeletal dysplasias", "of skeletal dysplasias that", "skeletal dysplasias that result", "dysplasias that result in", "that result in dwarfism", "in dwarfism reviewed", "dwarfism reviewed in", "reviewed in webster and", "in webster and donoghue", "and donoghue 1997", "1997 burke et", "1998 harada et", "et al 2009", "al 2009 .", "2009 . the", "the most common form", "most common form of", "common form of human", "form of human dwarfism", "of human dwarfism is", "human dwarfism is achondroplasia", "is achondroplasia ach", "ach which", "which is caused by", "is caused by mutations", "caused by mutations g380r", "by mutations g380r and", "mutations g380r and g375c", "g380r and g375c in", "and g375c in the", "g375c in the transmembrane", "in the transmembrane domain", "the transmembrane domain of", "transmembrane domain of fgfr3", "domain of fgfr3 that", "of fgfr3 that are", "fgfr3 that are thought", "that are thought to", "are thought to promote", "thought to promote ligand", "to promote ligand independent", "promote ligand independent dimerization", "independent dimerization rousseau", "dimerization rousseau et", "et al 1994", "1994 shiang et", "1994 bellus et", "et al 1995a", "1995a hypochondroplasia", "hch is a", "is a milder form", "a milder form dwarfism", "milder form dwarfism that", "form dwarfism that is", "dwarfism that is the", "that is the result", "is the result of", "the result of mutations", "result of mutations in", "of mutations in the", "mutations in the tyrosine", "in the tyrosine kinase", "the tyrosine kinase domain", "tyrosine kinase domain of", "kinase domain of fgfr3", "of fgfr3 bellus", "fgfr3 bellus et", "et al 1995b", "al 1995b .", "1995b . two", ". two neonatal", "two neonatal lethal conditions", "lethal conditions thanatophoric", "conditions thanatophoric dysplasia", "thanatophoric dysplasia type i", "dysplasia type i and", "type i and ii", "and ii tdi", "ii tdi and", "and tdii are", "tdii are also", "are also the result", "also the result of", "of mutations in fgfr3", "in fgfr3 tdi", "fgfr3 tdi arises", "tdi arises from a", "arises from a range", "from a range of", "a range of mutations", "range of mutations that", "of mutations that either", "mutations that either result", "that either result in", "either result in the", "result in the formation", "in the formation of", "the formation of unpaired", "formation of unpaired cysteine", "of unpaired cysteine residues", "unpaired cysteine residues in", "cysteine residues in the", "residues in the extracellular", "in the extracellular region", "the extracellular region that", "extracellular region that promote", "region that promote aberrant", "that promote aberrant ligand", "promote aberrant ligand independent", "aberrant ligand independent dimerization", "ligand independent dimerization or", "independent dimerization or by", "dimerization or by mutations", "or by mutations that", "by mutations that introduce", "mutations that introduce stop", "that introduce stop codons", "stop codons rousseau", "codons rousseau et", "et al 1995", "1995 rousseau et", "et al 1996", "1996 d'avis et", "d'avis et al 1998", "et al 1998 .", "1998 . a", ". a single", "single mutation k650e", "mutation k650e in", "k650e in the second", "in the second tyrosine", "the second tyrosine kinase", "second tyrosine kinase domain", "domain of fgfr3 is", "of fgfr3 is responsible", "fgfr3 is responsible for", "is responsible for all", "responsible for all identified", "for all identified cases", "all identified cases of", "identified cases of tdii", "of tdii tavormina", "tdii tavormina et", "1995a b .", "b . other", ". other missense", "other missense mutations at", "missense mutations at the", "mutations at the same", "at the same k650", "the same k650 residue", "same k650 residue give", "k650 residue give rise", "residue give rise to", "give rise to severe", "rise to severe achondroplasia", "to severe achondroplasia with", "severe achondroplasia with developmental", "achondroplasia with developmental disorders", "with developmental disorders and", "developmental disorders and acanthosis", "disorders and acanthosis nigricans", "acanthosis nigricans saddan", "syndrome tavormina et", "et al 1999", "1999 bellus et", "al 1999 .", "the severity of the", "severity of the phenotype", "of the phenotype arising", "the phenotype arising from", "phenotype arising from many", "arising from many of", "from many of the", "many of the activating", "of the activating fgfr3", "the activating fgfr3 mutations", "activating fgfr3 mutations has", "fgfr3 mutations has recently", "mutations has recently been", "has recently been shown", "recently been shown to", "been shown to correlate", "shown to correlate with", "to correlate with the", "correlate with the extent", "with the extent to", "the extent to which", "extent to which the", "to which the mutations", "which the mutations activate", "the mutations activate the", "mutations activate the receptor", "the receptor naski", "receptor naski et", "1996 bellus et", "et al 2000", "2000

              in addition", "

              in addition to mutations", "addition to mutations that", "to mutations that cause", "mutations that cause dwarfism", "that cause dwarfism syndromes", "dwarfism syndromes a", "syndromes a pro250arg", "a pro250arg mutation in", "pro250arg mutation in the", "mutation in the conserved", "in the conserved dipeptide", "the conserved dipeptide between", "conserved dipeptide between the", "dipeptide between the igii", "between the igii and", "the igii and igiii", "igii and igiii domains", "and igiii domains has", "igiii domains has been", "domains has been identified", "has been identified in", "been identified in an", "identified in an atypical", "in an atypical craniosynostosis", "an atypical craniosynostosis condition", "craniosynostosis condition bellus", "condition bellus et", "1996 reardon et", "et al 1997", "al 1997 .", "1997 . this", ". this mutation", "this mutation which", "mutation which is", "which is paralogous to", "is paralogous to mutations", "paralogous to mutations seen", "to mutations seen in", "mutations seen in fgfr1", "seen in fgfr1 and", "in fgfr1 and 2", "fgfr1 and 2 in", "and 2 in pfeiffer", "2 in pfeiffer and", "in pfeiffer and apert", "pfeiffer and apert syndrome", "apert syndrome respectively", "respectively results in", "results in an increase", "in an increase in", "an increase in ligand", "increase in ligand binding", "in ligand binding affinity", "ligand binding affinity for", "binding affinity for the", "affinity for the receptor", "the receptor ibrahimi", "receptor ibrahimi et", "et al 2004b", "al 2004b .


              of", "2004b .


              of all the", ".


              of all the fgf", "all the fgf receptors", "fgf receptors fgfr3", "receptors fgfr3 has", "fgfr3 has perhaps the", "has perhaps the best", "perhaps the best established", "the best established link", "best established link to", "established link to the", "link to the development", "to the development in", "the development in cancer.", "in cancer. 50%", "cancer. 50% of", "50% of bladder cancers", "of bladder cancers have", "bladder cancers have somatic", "cancers have somatic mutations", "have somatic mutations in", "somatic mutations in the", "mutations in the coding", "in the coding sequence", "the coding sequence of", "coding sequence of fgfr3", "of fgfr3 of", "fgfr3 of these", "of these more", "these more than", "more than half occur", "than half occur in", "half occur in the", "occur in the extracellular", "the extracellular region at", "extracellular region at a", "region at a single", "at a single position", "single position s249c", "s249c cappellen", "1999 naski et", "1996 di martino", "di martino et al", "2009 sibley et", "et al 2001", "al 2001 .", "2001 . activating", ". activating mutations", "activating mutations are also", "mutations are also seen", "are also seen in", "also seen in the", "seen in the juxta", "the juxta and", "juxta and trans", "and trans membrane domains", "membrane domains as", "domains as well", "as well as in", "well as in the", "as in the kinase", "in the kinase domain", "kinase domain reviewed", "domain reviewed in", "reviewed in weshe et", "in weshe et al", "et al 2011", "al 2011 .", "2011 . as", ". as is", "as is the case", "is the case for", "the case for the", "case for the other", "for the other receptors", "other receptors many", "receptors many of", "of the activating mutations", "the activating mutations that", "activating mutations that are", "mutations that are seen", "that are seen in", "are seen in fgfr3", "seen in fgfr3 related", "in fgfr3 related cancers", "fgfr3 related cancers mimic", "related cancers mimic the", "cancers mimic the germline", "mimic the germline fgfr3", "the germline fgfr3 mutations", "germline fgfr3 mutations that", "fgfr3 mutations that give", "mutations that give rise", "that give rise to", "give rise to autosomal", "rise to autosomal skeletal", "to autosomal skeletal disorders", "autosomal skeletal disorders and", "skeletal disorders and include", "disorders and include both", "and include both ligand", "include both ligand dependent", "both ligand dependent and", "ligand dependent and independent", "dependent and independent mechanisms", "independent mechanisms reviewed", "mechanisms reviewed in", "1998 . in addition", ". in addition to", "in addition to activating", "addition to activating mutations", "activating mutations the", "mutations the fgfr3", "the fgfr3 gene is", "fgfr3 gene is subject", "gene is subject to", "is subject to a", "subject to a translocation", "to a translocation event", "a translocation event in", "translocation event in 15%", "event in 15% of", "in 15% of multiple", "15% of multiple myelomas", "multiple myelomas avet", "myelomas avet loiseau", "avet loiseau et al", "1998 chesi et", ". this chromosomal", "this chromosomal rearrangement puts", "chromosomal rearrangement puts the", "rearrangement puts the fgfr3", "puts the fgfr3 gene", "the fgfr3 gene under", "fgfr3 gene under the", "gene under the control", "under the control of", "the control of the", "control of the highly", "of the highly active", "the highly active igh", "highly active igh promoter", "active igh promoter and", "igh promoter and promotes", "promoter and promotes overexpression", "and promotes overexpression and", "promotes overexpression and constitutive", "overexpression and constitutive activation", "and constitutive activation of", "constitutive activation of fgfr3.", "of fgfr3. in", "fgfr3. in a", "in a small proportion", "a small proportion of", "small proportion of multiple", "proportion of multiple myelomas", "multiple myelomas the", "myelomas the translocation", "the translocation event is", "translocation event is accompanied", "event is accompanied by", "is accompanied by activating", "accompanied by activating mutations", "by activating mutations in", "activating mutations in the", "mutations in the fgfr3", "in the fgfr3 coding", "the fgfr3 coding sequence", "coding sequence chesi", "sequence chesi et", "al 1997 .

              more", ".

              more recently a", "recently a number", "a number of fusion", "number of fusion proteins", "of fusion proteins of", "fusion proteins of fgfr3", "proteins of fgfr3 have", "of fgfr3 have been", "fgfr3 have been identified", "have been identified in", "been identified in various", "identified in various cancers", "various cancers singh", "cancers singh et", "et al 2012", "2012 williams et", "et al 2013", "2013 parker et", "2013 wu et", "2013 wang et", "et al 2014", "2014 yuan et", "2014 reviewed in", "reviewed in parker et", "in parker et al", "al 2014 .", "2014 . the most", ". the most common", "the most common fusion", "most common fusion protein", "common fusion protein is", "fusion protein is tacc3", "is tacc3 a", "tacc3 a coiled", "a coiled coil protein", "coiled coil protein involved", "coil protein involved in", "protein involved in mitotic", "involved in mitotic spindle", "in mitotic spindle assembly.", "spindle assembly. fgfr3", "assembly. fgfr3 fusion", "fgfr3 fusion proteins are", "fusion proteins are constitutively", "proteins are constitutively active", "are constitutively active and", "constitutively active and appear", "active and appear to", "and appear to contribute", "appear to contribute to", "to contribute to proliferation", "contribute to proliferation and", "to proliferation and tumorigenesis", "proliferation and tumorigenesis through", "and tumorigenesis through activation", "tumorigenesis through activation of", "through activation of the", "activation of the erk", "of the erk and", "the erk and akt", "erk and akt signaling", "and akt signaling pathways", "signaling pathways reviewed", "pathways reviewed in", "the fgfr3 gene has been", "fgfr3 gene has been shown", "gene has been shown to", "has been shown to be", "been shown to be subject", "shown to be subject to", "to be subject to activating", "be subject to activating mutations", "subject to activating mutations and", "to activating mutations and gene", "activating mutations and gene amplification", "mutations and gene amplification leading", "and gene amplification leading to", "gene amplification leading to a", "amplification leading to a variety", "leading to a variety of", "to a variety of proliferative", "a variety of proliferative and", "variety of proliferative and developmental", "of proliferative and developmental disorders", "proliferative and developmental disorders depending", "and developmental disorders depending on", "developmental disorders depending on whether", "disorders depending on whether these", "depending on whether these events", "on whether these events occur", "whether these events occur in", "these events occur in the", "events occur in the germline", "occur in the germline or", "in the germline or arise", "the germline or arise somatically.", "or arise somatically.

              activating", "arise somatically.

              activating mutations", "somatically.

              activating mutations in", "

              activating mutations in fgfr3 are", "mutations in fgfr3 are associated", "in fgfr3 are associated with", "fgfr3 are associated with the", "are associated with the development", "associated with the development of", "with the development of a", "the development of a range", "development of a range of", "of a range of skeletal", "a range of skeletal dysplasias", "range of skeletal dysplasias that", "of skeletal dysplasias that result", "skeletal dysplasias that result in", "dysplasias that result in dwarfism", "result in dwarfism reviewed", "in dwarfism reviewed in", "dwarfism reviewed in webster", "reviewed in webster and donoghue", "webster and donoghue 1997", "donoghue 1997 burke", "1997 burke et al", "burke et al 1998", "al 1998 harada", "1998 harada et al", "harada et al 2009", "et al 2009 .", "2009 . the most", "the most common form of", "most common form of human", "common form of human dwarfism", "form of human dwarfism is", "of human dwarfism is achondroplasia", "dwarfism is achondroplasia ach", "ach which is", "which is caused by mutations", "is caused by mutations g380r", "caused by mutations g380r and", "by mutations g380r and g375c", "mutations g380r and g375c in", "g380r and g375c in the", "and g375c in the transmembrane", "g375c in the transmembrane domain", "in the transmembrane domain of", "the transmembrane domain of fgfr3", "transmembrane domain of fgfr3 that", "domain of fgfr3 that are", "of fgfr3 that are thought", "fgfr3 that are thought to", "that are thought to promote", "are thought to promote ligand", "thought to promote ligand independent", "to promote ligand independent dimerization", "ligand independent dimerization rousseau", "independent dimerization rousseau et", "dimerization rousseau et al", "rousseau et al 1994", "al 1994 shiang", "1994 shiang et al", "shiang et al 1994", "al 1994 bellus", "1994 bellus et al", "bellus et al 1995a", "hypochondroplasia hch is", "hch is a milder", "is a milder form dwarfism", "a milder form dwarfism that", "milder form dwarfism that is", "form dwarfism that is the", "dwarfism that is the result", "that is the result of", "is the result of mutations", "the result of mutations in", "result of mutations in the", "of mutations in the tyrosine", "mutations in the tyrosine kinase", "in the tyrosine kinase domain", "the tyrosine kinase domain of", "tyrosine kinase domain of fgfr3", "domain of fgfr3 bellus", "of fgfr3 bellus et", "fgfr3 bellus et al", "bellus et al 1995b", "et al 1995b .", "1995b . two neonatal", ". two neonatal lethal", "neonatal lethal conditions thanatophoric", "lethal conditions thanatophoric dysplasia", "conditions thanatophoric dysplasia type", "thanatophoric dysplasia type i and", "dysplasia type i and ii", "i and ii tdi", "and ii tdi and", "ii tdi and tdii", "tdi and tdii are", "and tdii are also", "tdii are also the", "are also the result of", "also the result of mutations", "result of mutations in fgfr3", "mutations in fgfr3 tdi", "in fgfr3 tdi arises", "fgfr3 tdi arises from", "tdi arises from a range", "arises from a range of", "from a range of mutations", "a range of mutations that", "range of mutations that either", "of mutations that either result", "mutations that either result in", "that either result in the", "either result in the formation", "result in the formation of", "in the formation of unpaired", "the formation of unpaired cysteine", "formation of unpaired cysteine residues", "of unpaired cysteine residues in", "unpaired cysteine residues in the", "cysteine residues in the extracellular", "residues in the extracellular region", "in the extracellular region that", "the extracellular region that promote", "extracellular region that promote aberrant", "region that promote aberrant ligand", "that promote aberrant ligand independent", "promote aberrant ligand independent dimerization", "aberrant ligand independent dimerization or", "ligand independent dimerization or by", "independent dimerization or by mutations", "dimerization or by mutations that", "or by mutations that introduce", "by mutations that introduce stop", "mutations that introduce stop codons", "introduce stop codons rousseau", "stop codons rousseau et", "codons rousseau et al", "rousseau et al 1995", "al 1995 rousseau", "1995 rousseau et al", "rousseau et al 1996", "al 1996 d'avis", "1996 d'avis et al", "d'avis et al 1998 .", "al 1998 . a", "1998 . a single", ". a single mutation", "a single mutation k650e", "single mutation k650e in", "mutation k650e in the", "k650e in the second tyrosine", "in the second tyrosine kinase", "the second tyrosine kinase domain", "second tyrosine kinase domain of", "kinase domain of fgfr3 is", "domain of fgfr3 is responsible", "of fgfr3 is responsible for", "fgfr3 is responsible for all", "is responsible for all identified", "responsible for all identified cases", "for all identified cases of", "all identified cases of tdii", "cases of tdii tavormina", "of tdii tavormina et", "tdii tavormina et al", "tavormina et al 1995a", "al 1995a b", "b . other missense", ". other missense mutations", "other missense mutations at the", "missense mutations at the same", "mutations at the same k650", "at the same k650 residue", "the same k650 residue give", "same k650 residue give rise", "k650 residue give rise to", "residue give rise to severe", "give rise to severe achondroplasia", "rise to severe achondroplasia with", "to severe achondroplasia with developmental", "severe achondroplasia with developmental disorders", "achondroplasia with developmental disorders and", "with developmental disorders and acanthosis", "developmental disorders and acanthosis nigricans", "and acanthosis nigricans saddan", "nigricans saddan syndrome", "saddan syndrome tavormina", "syndrome tavormina et al", "tavormina et al 1999", "al 1999 bellus", "1999 bellus et al", "bellus et al 1999", "et al 1999 .", "1999 . the", ". the severity", "the severity of the phenotype", "severity of the phenotype arising", "of the phenotype arising from", "the phenotype arising from many", "phenotype arising from many of", "arising from many of the", "from many of the activating", "many of the activating fgfr3", "of the activating fgfr3 mutations", "the activating fgfr3 mutations has", "activating fgfr3 mutations has recently", "fgfr3 mutations has recently been", "mutations has recently been shown", "has recently been shown to", "recently been shown to correlate", "been shown to correlate with", "shown to correlate with the", "to correlate with the extent", "correlate with the extent to", "with the extent to which", "the extent to which the", "extent to which the mutations", "to which the mutations activate", "which the mutations activate the", "the mutations activate the receptor", "activate the receptor naski", "the receptor naski et", "receptor naski et al", "naski et al 1996", "al 1996 bellus", "1996 bellus et al", "bellus et al 2000", "al 2000

              in", "2000

              in addition to", "

              in addition to mutations that", "addition to mutations that cause", "to mutations that cause dwarfism", "mutations that cause dwarfism syndromes", "cause dwarfism syndromes a", "dwarfism syndromes a pro250arg", "syndromes a pro250arg mutation", "a pro250arg mutation in the", "pro250arg mutation in the conserved", "mutation in the conserved dipeptide", "in the conserved dipeptide between", "the conserved dipeptide between the", "conserved dipeptide between the igii", "dipeptide between the igii and", "between the igii and igiii", "the igii and igiii domains", "igii and igiii domains has", "and igiii domains has been", "igiii domains has been identified", "domains has been identified in", "has been identified in an", "been identified in an atypical", "identified in an atypical craniosynostosis", "in an atypical craniosynostosis condition", "atypical craniosynostosis condition bellus", "craniosynostosis condition bellus et", "condition bellus et al", "bellus et al 1996", "al 1996 reardon", "1996 reardon et al", "reardon et al 1997", "et al 1997 .", "1997 . this mutation", "this mutation which is", "mutation which is paralogous", "which is paralogous to mutations", "is paralogous to mutations seen", "paralogous to mutations seen in", "to mutations seen in fgfr1", "mutations seen in fgfr1 and", "seen in fgfr1 and 2", "in fgfr1 and 2 in", "fgfr1 and 2 in pfeiffer", "and 2 in pfeiffer and", "2 in pfeiffer and apert", "in pfeiffer and apert syndrome", "and apert syndrome respectively", "syndrome respectively results", "respectively results in an", "results in an increase in", "in an increase in ligand", "an increase in ligand binding", "increase in ligand binding affinity", "in ligand binding affinity for", "ligand binding affinity for the", "binding affinity for the receptor", "for the receptor ibrahimi", "the receptor ibrahimi et", "receptor ibrahimi et al", "ibrahimi et al 2004b", "et al 2004b .


              of", "al 2004b .


              of all", "2004b .


              of all the fgf", ".


              of all the fgf receptors", "the fgf receptors fgfr3", "fgf receptors fgfr3 has", "receptors fgfr3 has perhaps", "fgfr3 has perhaps the best", "has perhaps the best established", "perhaps the best established link", "the best established link to", "best established link to the", "established link to the development", "link to the development in", "to the development in cancer.", "development in cancer. 50%", "in cancer. 50% of", "cancer. 50% of bladder", "50% of bladder cancers have", "of bladder cancers have somatic", "bladder cancers have somatic mutations", "cancers have somatic mutations in", "have somatic mutations in the", "somatic mutations in the coding", "mutations in the coding sequence", "in the coding sequence of", "the coding sequence of fgfr3", "sequence of fgfr3 of", "of fgfr3 of these", "of these more than", "these more than half", "more than half occur in", "than half occur in the", "half occur in the extracellular", "occur in the extracellular region", "in the extracellular region at", "the extracellular region at a", "extracellular region at a single", "region at a single position", "a single position s249c", "s249c cappellen et", "cappellen et al 1999", "al 1999 naski", "1999 naski et al", "al 1996 di", "1996 di martino et", "martino et al 2009", "al 2009 sibley", "2009 sibley et al", "sibley et al 2001", "et al 2001 .", "2001 . activating mutations", ". activating mutations are", "activating mutations are also seen", "mutations are also seen in", "are also seen in the", "also seen in the juxta", "in the juxta and", "the juxta and trans", "juxta and trans membrane", "trans membrane domains as", "membrane domains as well", "domains as well as", "as well as in the", "well as in the kinase", "as in the kinase domain", "the kinase domain reviewed", "kinase domain reviewed in", "domain reviewed in weshe", "reviewed in weshe et al", "weshe et al 2011", "et al 2011 .", "2011 . as is", ". as is the", "as is the case for", "is the case for the", "the case for the other", "case for the other receptors", "the other receptors many", "other receptors many of", "receptors many of the", "many of the activating mutations", "of the activating mutations that", "the activating mutations that are", "activating mutations that are seen", "mutations that are seen in", "that are seen in fgfr3", "are seen in fgfr3 related", "seen in fgfr3 related cancers", "in fgfr3 related cancers mimic", "fgfr3 related cancers mimic the", "related cancers mimic the germline", "cancers mimic the germline fgfr3", "mimic the germline fgfr3 mutations", "the germline fgfr3 mutations that", "germline fgfr3 mutations that give", "fgfr3 mutations that give rise", "mutations that give rise to", "that give rise to autosomal", "give rise to autosomal skeletal", "rise to autosomal skeletal disorders", "to autosomal skeletal disorders and", "autosomal skeletal disorders and include", "skeletal disorders and include both", "disorders and include both ligand", "and include both ligand dependent", "include both ligand dependent and", "both ligand dependent and independent", "ligand dependent and independent mechanisms", "and independent mechanisms reviewed", "independent mechanisms reviewed in", "mechanisms reviewed in webster", "al 1998 . in", "1998 . in addition to", ". in addition to activating", "in addition to activating mutations", "to activating mutations the", "activating mutations the fgfr3", "mutations the fgfr3 gene", "the fgfr3 gene is subject", "fgfr3 gene is subject to", "gene is subject to a", "is subject to a translocation", "subject to a translocation event", "to a translocation event in", "a translocation event in 15%", "translocation event in 15% of", "event in 15% of multiple", "in 15% of multiple myelomas", "of multiple myelomas avet", "multiple myelomas avet loiseau", "myelomas avet loiseau et", "loiseau et al 1998", "al 1998 chesi", "1998 chesi et al", "chesi et al 1997", "1997 . this chromosomal", ". this chromosomal rearrangement", "this chromosomal rearrangement puts the", "chromosomal rearrangement puts the fgfr3", "rearrangement puts the fgfr3 gene", "puts the fgfr3 gene under", "the fgfr3 gene under the", "fgfr3 gene under the control", "gene under the control of", "under the control of the", "the control of the highly", "control of the highly active", "of the highly active igh", "the highly active igh promoter", "highly active igh promoter and", "active igh promoter and promotes", "igh promoter and promotes overexpression", "promoter and promotes overexpression and", "and promotes overexpression and constitutive", "promotes overexpression and constitutive activation", "overexpression and constitutive activation of", "and constitutive activation of fgfr3.", "activation of fgfr3. in", "of fgfr3. in a", "fgfr3. in a small", "in a small proportion of", "a small proportion of multiple", "small proportion of multiple myelomas", "of multiple myelomas the", "multiple myelomas the translocation", "myelomas the translocation event", "the translocation event is accompanied", "translocation event is accompanied by", "event is accompanied by activating", "is accompanied by activating mutations", "accompanied by activating mutations in", "by activating mutations in the", "activating mutations in the fgfr3", "mutations in the fgfr3 coding", "in the fgfr3 coding sequence", "fgfr3 coding sequence chesi", "coding sequence chesi et", "sequence chesi et al", "et al 1997 .

              more", "al 1997 .

              more recently", "1997 .

              more recently a", ".

              more recently a number", "recently a number of", "a number of fusion proteins", "number of fusion proteins of", "of fusion proteins of fgfr3", "fusion proteins of fgfr3 have", "proteins of fgfr3 have been", "of fgfr3 have been identified", "fgfr3 have been identified in", "have been identified in various", "been identified in various cancers", "in various cancers singh", "various cancers singh et", "cancers singh et al", "singh et al 2012", "al 2012 williams", "2012 williams et al", "williams et al 2013", "al 2013 parker", "2013 parker et al", "parker et al 2013", "al 2013 wu", "2013 wu et al", "wu et al 2013", "al 2013 wang", "2013 wang et al", "wang et al 2014", "al 2014 yuan", "2014 yuan et al", "yuan et al 2014", "al 2014 reviewed", "2014 reviewed in parker", "reviewed in parker et al", "parker et al 2014", "et al 2014 .", "al 2014 . the", "2014 . the most common", ". the most common fusion", "the most common fusion protein", "most common fusion protein is", "common fusion protein is tacc3", "protein is tacc3 a", "is tacc3 a coiled", "tacc3 a coiled coil", "a coiled coil protein involved", "coiled coil protein involved in", "coil protein involved in mitotic", "protein involved in mitotic spindle", "involved in mitotic spindle assembly.", "mitotic spindle assembly. fgfr3", "spindle assembly. fgfr3 fusion", "assembly. fgfr3 fusion proteins", "fgfr3 fusion proteins are constitutively", "fusion proteins are constitutively active", "proteins are constitutively active and", "are constitutively active and appear", "constitutively active and appear to", "active and appear to contribute", "and appear to contribute to", "appear to contribute to proliferation", "to contribute to proliferation and", "contribute to proliferation and tumorigenesis", "to proliferation and tumorigenesis through", "proliferation and tumorigenesis through activation", "and tumorigenesis through activation of", "tumorigenesis through activation of the", "through activation of the erk", "activation of the erk and", "of the erk and akt", "the erk and akt signaling", "erk and akt signaling pathways", "akt signaling pathways reviewed", "signaling pathways reviewed in", "pathways reviewed in parker" ] }, { "record_id": "GLY_000594_1_1872", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9634597", "r hsa", "hsa 9634597", "r hsa 9634597" ] }, { "record_id": "GLY_000594_1_1872", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "gper1 signaling", "also known", "known as", "as gpr30", "is an", "an orphan", "orphan g", "g protein", "protein coupled", "coupled receptor", "receptor that", "that has", "has been", "been suggested", "suggested to", "to act", "act as", "as an", "an alternate", "alternate estrogen", "estrogen receptor", "revankar et", "et al", "filardo et", "reviewed in", "in prossnitz", "prossnitz and", "and barton", "gaudet et", "2015 .", ". in", "in support", "support of", "of this", "a number", "number of", "of studies", "studies have", "have shown", "shown that", "that gper1", "gper1 stimulates", "stimulates mapk", "mapk and", "and camp", "camp activation", "activation in", "in response", "response to", "to estrogen", "estrogen in", "in esr1", "esr1 negative", "negative breast", "breast cancer", "cancer cells.", "cells. similar", "similar to", "to classical", "classical esr1", "esr1 mediated", "mediated signaling", "this estrogen", "estrogen responsive", "responsive gper1", "gper1 is", "is suggested", "act through", "through g", "g beta", "beta gamma", "gamma and", "and to", "to involve", "involve egfr", "egfr transactivation", "in filardo", "filardo and", "and thomas", "2012 .", "gper1 also", "also known as", "known as gpr30", "gpr30 is", "is an orphan", "an orphan g", "orphan g protein", "g protein coupled", "protein coupled receptor", "coupled receptor that", "receptor that has", "that has been", "has been suggested", "been suggested to", 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mediated", "esr1 mediated signaling", "signaling this", "this estrogen responsive", "estrogen responsive gper1", "responsive gper1 is", "gper1 is suggested", "is suggested to", "to act through", "act through g", "through g beta", "g beta gamma", "beta gamma and", "gamma and to", "and to involve", "to involve egfr", "involve egfr transactivation", "transactivation filardo", "al 2000", "2000 filardo", "al 2002", "2002 reviewed", "reviewed in filardo", "in filardo and", "filardo and thomas", "thomas 2012", "gper1 also known", "also known as gpr30", "as gpr30 is", "gpr30 is an", "is an orphan g", "an orphan g protein", "orphan g protein coupled", "g protein coupled receptor", "protein coupled receptor that", "coupled receptor that has", "receptor that has been", "that has been suggested", "has been suggested to", "been suggested to act", "suggested to act as", "to act as an", "act as an alternate", "as an alternate estrogen", "an alternate estrogen receptor", "estrogen receptor revankar", "receptor revankar et", "et al 2005", "2005 filardo et", "et al 2007", "2007 reviewed in", "reviewed in prossnitz and", "in prossnitz and barton", "and barton 2011", "2011 gaudet et", "et al 2015", "al 2015 .", "2015 . in support", ". in support of", "in support of this", "of this a", "this a number", "a number of studies", "number of studies have", "of studies have shown", "studies have shown that", "have shown that gper1", "shown that gper1 stimulates", "that gper1 stimulates mapk", "gper1 stimulates mapk and", "stimulates mapk and camp", "mapk and camp activation", "and camp activation in", "camp activation in response", "activation in response to", "in response to estrogen", "response to estrogen in", "to estrogen in esr1", "estrogen in esr1 negative", "in esr1 negative breast", "esr1 negative breast cancer", "negative breast cancer cells.", "breast cancer cells. similar", "cancer cells. similar to", "cells. similar to classical", "similar to classical esr1", "to classical esr1 mediated", "classical esr1 mediated signaling", "mediated signaling this", "signaling this estrogen", "this estrogen responsive gper1", "estrogen responsive gper1 is", "responsive gper1 is suggested", "gper1 is suggested to", "is suggested to act", "suggested to act through", "to act through g", "act through g beta", "through g beta gamma", "g beta gamma and", "beta gamma and to", "gamma and to involve", "and to involve egfr", "to involve egfr transactivation", "egfr transactivation filardo", "transactivation filardo et", "et al 2000", "2000 filardo et", "et al 2002", "2002 reviewed in", "reviewed in filardo and", "in filardo and thomas", "and thomas 2012", "thomas 2012 .", "gper1 also known as", "known as gpr30 is", "as gpr30 is an", "gpr30 is an orphan", "is an orphan g protein", "an orphan g protein coupled", "orphan g protein coupled receptor", "g protein coupled receptor that", "protein coupled receptor that has", "coupled receptor that has been", "receptor that has been 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mapk and camp activation", "mapk and camp activation in", "and camp activation in response", "camp activation in response to", "activation in response to estrogen", "in response to estrogen in", "response to estrogen in esr1", "to estrogen in esr1 negative", "estrogen in esr1 negative breast", "in esr1 negative breast cancer", "esr1 negative breast cancer cells.", "negative breast cancer cells. similar", "breast cancer cells. similar to", "cancer cells. similar to classical", "cells. similar to classical esr1", "similar to classical esr1 mediated", "to classical esr1 mediated signaling", "esr1 mediated signaling this", "mediated signaling this estrogen", "signaling this estrogen responsive", "this estrogen responsive gper1 is", "estrogen responsive gper1 is suggested", "responsive gper1 is suggested to", "gper1 is suggested to act", "is suggested to act through", "suggested to act through g", "to act through g beta", "act through g beta gamma", "through g beta gamma and", "g beta gamma and to", "beta gamma and to involve", "gamma and to involve egfr", "and to involve egfr transactivation", "involve egfr transactivation filardo", "egfr transactivation filardo et", "transactivation filardo et al", "filardo et al 2000", "al 2000 filardo", "2000 filardo et al", "filardo et al 2002", "al 2002 reviewed", "2002 reviewed in filardo", "reviewed in filardo and thomas", "filardo and thomas 2012", "and thomas 2012 ." ] }, { "record_id": "GLY_000594_1_1873", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9705671", "r hsa", "hsa 9705671", "r hsa 9705671" ] }, { "record_id": "GLY_000594_1_1873", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 2", "2 activates/modulates", "activates/modulates innate", "innate and", "and adaptive", "adaptive immune", "immune responses", "sars cov 2", "cov 2 activates/modulates", "2 activates/modulates innate", "activates/modulates innate 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means", "means of", "of tlr7", "tlr7 and", "which detect", "detect gu", "gu rich", "rich ssrna", "ssrna sequences", ". second", "2 dsrna", "dsrna replication", "replication intermediates", "intermediates can", "can be", "be recognized", "by cytoplasmic", "cytoplasmic receptors", "receptors ddx58", "ddx58 and", "and ifih1", "ifih1 which", "which bind", "bind to", "to mitochondrial", "mitochondrial antiviral", "antiviral signaling", "signaling protein", "ips 1", "to induce", "induce the", "the ifn", "ifn mediated", "mediated antiviral", "antiviral response", "yin x", "x et", ". in", "in addition", "2 e", "e can", "be sensed", "sensed by", "by tlr2", "zheng m", "m et", ". further", "cellular nucleic", "nucleic acid", "acid binding", "binding protein", "and la", "la related", "related protein", "can directly", "directly bind", "bind sars", "2 grna", "grna to", "to repress", "repress sars", "2 replication", "schmidt n", "n et", ". this", "this module", "module also", "also describes", "describes several", "several strategies", "strategies developed", "developed by", "by sars", "2 to", "to evade", "evade or", "or alter", "alter host", "host immunity", "including escaping", "escaping innate", "immune sensors", "inhibiting ifn", "ifn production", "production and", "and signaling", "and evading", "evading antiviral", "antiviral function", "function of", "of ifn", "ifn stimulated", "stimulated gene", "products. for", "for example", "2 encodes", "encodes nsp14", "nsp14 and", "and nsp16", "nsp16 which", "which possess", "possess guanine", "guanine n7", "n7 methyltransferase", "methyltransferase activity", "activity and", "and 2\u2019", "2\u2019 o", "o methyl", "methyl transferase", "transferase activity", "activity respectively", "ogando ns", "ns et", "al. 2020", "krafcikova p", "viswanatha t", "t et", "lin s", "yan l", "l et", "in human", "human coronaviruses", "coronaviruses nsp14", "nsp14 generates", "generates 5'", "5' cap", "cap 0", "0 viral", "viral rna", "n7 methylated", "nsp16 further", "further methylates", "methylates cap", "viral rna.", "rna. these", "these viral", "rna modifications", "modifications mimic", "mimic the", "the 5'", "cap structure", "structure of", "of host", "host mrnas", "mrnas allowing", "allowing the", "the virus", "virus to", "to efficiently", "efficiently evade", "evade recognition", "recognition by", "by cytosolic", "cytosolic ddx58", "chen y", "y et", "al. 2009", "daffis s", "al. 2010", "shown for", "for covs", "covs such", "as sars", "cov 1", "1 and", "and mers", "mers cov", "cov .", ". structural", "structural studies", "studies and", "and computational", "computational analysis", "analysis suggest", "suggest that", "that properties", "properties and", "and biological", "biological functions", "functions of", "of sars", "2 nsp14", "nsp16 could", "could be", "be very", "very similar", "similar to", "to these", "these of", "rosas lemus", "lemus m", "viswanathan t", "jiang y", "wilamowski m", "the uridylate\u2010specific", "uridylate\u2010specific endoribonuclease", "activity of", "2 nsp15", "nsp15 degrades", "degrades viral", "rna to", "to hide", "hide it", "it from", "from innate", "frazier mn", "mn et", ". moreover", "encodes several", "several proteins", "proteins that", "that directly", "to host", "host targets", "targets associated", "associated with", "with sars\u2011cov\u20112", "sars\u2011cov\u20112 infection", "infection and", "and cytokine", "cytokine production", "shin d", "d et", "xia h", "h et", "matsuyama t", "yuen ck", "ck et", "reviewed by", "by park", "park a", "a &", "& iwasaki", "iwasaki a", "a 2020", "2020 .", "several such", "such binding", "binding events", "events and", "and their", "their consequences.", "consequences. for", "as a", "a deubiquitinating", "deubiquitinating and", "and deisgylating", "deisgylating enzyme", "viral nsp3", "nsp3 binds", "binds to", "to and", "and removes", "removes isg15", "isg15 from", "from signaling", "signaling proteins", "proteins such", "as irf3", "irf3 and", "ifih1 thereby", "thereby modulating", "modulating the", "the formation", "formation of", "of signaling", "signaling complexes", "complexes and", "and the", "the activation", "activation of", "of irf3/7", "irf3/7 and", "and nf", "nf kappab", "liu cq", "cq et", ". binding", "binding of", "2 nsp6", "nsp13 or", "or membrane", "protein to", "to cytosolic", "cytosolic tbk1", "tbk1 prevents", "prevents irf3/7", "irf3/7 activation", "activation and", "and inhibits", "inhibits ifn", "production downstream", "downstream of", "of ddx58", "mavs and", "and sting", "sting signaling", "sui l", ". next", "m protein", "protein targets", "targets mavs", "mavs to", "to prevent", "prevent the", "the mavs", "mavs signalosome", "signalosome complex", "complex and", "and thereby", "thereby inhibits", "inhibits downstream", "downstream signaling", "pathways of", "fu yz", "yz et", "2 nucleocapsid", "to e3", "e3 ubiquitin", "ubiquitin ligase", "ligase trim25", "trim25 inhibits", "inhibits trim25", "trim25 mediated", "mediated ddx58", "ddx58 ubiquitination", "ubiquitination and", "the ddx58", "ddx58 signaling", "signaling pathway", "gori sg", "sg et", ". n", "n interacts", "interacts with", "with nlrp3", "nlrp3 to", "to promote", "promote the", "the assembly", "assembly and", "and activation", "the nlrp3", "nlrp3 inflammasome", "pan p", "the interaction", "interaction between", "between viral", "viral n", "n and", "and masp2", "masp2 promotes", "promotes masp2", "masp2 mediated", "mediated cleavage", "cleavage of", "of c4", "ali ym", "ym et", "and c2", "kang s", "leading to", "to the", "the hyperactivation", "hyperactivation of", "the complement", "complement system.", "system. besides", "n promotes", "promotes nf", "kappab activation", "activation by", "by targeting", "targeting signaling", "complexes of", "of tak1", "tak1 and", "and ikk", "wu y", "the ion", "ion channel", "channel activities", "activities of", "of accessory", "accessory protein", "protein orf3a", "orf3a or", "or 3a", "open reading", "reading frame", "frame 3a", "and sars\u2011cov\u20112", "sars\u2011cov\u20112 envelope", "protein contribute", "contribute to", "to activation", "inflammasome leading", "to highly", "highly inflammatory", "inflammatory pyroptotic", "pyroptotic cell", "cell death", "based on", "on findings", "findings for", "for sars", "siu kl", "kl et", "al. 2019", "2019 .", ". sars", "2 nsp5", "nsp5 protease", "cleaves tab1", "a component", "component of", "the tak1", "tak1 complex", "thus inhibiting", "inhibiting nf", "moustaqil m", "et al", "al .2021", ".2021 .", ". 3clpro", "3clpro targets", "targets nlrp12", "nlrp12 which", "which modulates", "modulates the", "the expression", "expression of", "of inflammatory", "inflammatory cytokines", "cytokines through", "through the", "the regulation", "regulation of", "the nfkappab", "nfkappab and", "and mapk", "mapk pathways", "2 6", "with importin", "importin kpna2", "kpna2 and", "and components", "components of", "the nuclear", "nuclear pore", "pore complex", "nup98 and", "and rae1", "to block", "block nuclear", "nuclear translocation", "translocation of", "of irf3", "stat1 and", "and stat2", "miorin l", "2 9b", "inhibits the", "mavs mediated", "mediated production", "production of", "of type", "i ifns", "ifns by", "targeting tomm70", "tomm70 on", "on the", "the mitochondria", "jiang hw", "hw et", "of mitochondrial", "mitochondrial viral", "viral 9", "9 to", "to ikbkg", "ikbkg prevents", "prevents mavs", "mavs dependent", "dependent nf", "wu j", "j et", ". although", "although the", "the evasion", "evasion mechanisms", "mechanisms are", "are mainly", "mainly conserved", "conserved between", "between sars", "and sars", "gordon de", "de et", "studies identified", "identified sars", "2 specific", "specific modulations", "modulations of", "host immune", "response that", "may contribute", "to pathophysiological", "pathophysiological determinants", "determinants of", "of covid", "covid 19", "schiller hb", "hb et", "several virus", "virus host", "host interactions", "interactions identified", "identified in", "in cells", "cells during", "during sars", "but not", "not sars", "infection. for", "2 8", "regulates the", "of class", "class i", "i mhc", "mhc on", "the surface", "surface of", "the infected", "cells through", "through an", "an autophagy", "autophagy dependent", "dependent lysosomal", "lysosomal degradation", "degradation of", "zhang y", ". at", "at the", "the plasma", "plasma membrane", "of secreted", "secreted viral", "viral 8", "8 to", "to il17ra", "il17ra activates", "activates il17", "il17 signaling", "pathway leading", "to an", "an increased", "increased secretion", "secretion of", "of cytokines/chemokines", "cytokines/chemokines thus", "thus contributing", "contributing to", "to cytokine", "cytokine storm", "storm during", "2 infection", "lin x", ". furthermore", "2 host", "host interactome", "interactome and", "and proteomics", "proteomics studies", "identified various", "various human", "human proteins", "that are", "are targeted", "targeted by", "2 proteins", "al. 2020a", "bojkova d", "stukalov a", "li j", "messina f", "f et", "module does", "does not", "not cover", "cover all", "all identified", "cov 2\u2013human", "2\u2013human interactions", "the module", "describes those", "those associations", "associations that", "that were", "were functionally", "functionally validated.", "coronaviruses covs", "covs are", "are positive sense", "positive sense rna", "sense rna viruses", "rna viruses that", "viruses that replicate", "that replicate in", "replicate in the", "in the interior", "the interior of", "interior of double", "of double membrane", "double membrane vesicles", "vesicles dmv", "dmv in", "in the cytoplasm", "the cytoplasm of", "cytoplasm of infected", "of infected cells", "cells stertz", "stertz s et", "s et al.", "et al. 2007", "2007 knoops", "knoops k et", "k et al.", "et al. 2008", "2008 v'kovski", "v'kovski p et", "p et al.", "et al. 2021", "al. 2021 .", "2021 . the", ". the viral", "the viral replication", "viral replication and", "replication and transcription", "and transcription are", "transcription are facilitated", "are facilitated by", "facilitated by virus", "by virus encoded", "virus encoded non", "encoded non structural", "non structural proteins", "proteins sars", "cov 2 nsp1\u2013nsp16", "nsp1\u2013nsp16 that", "that assemble to", "assemble to form", "to form a", "form a dmv", "a dmv bound", "dmv bound replication", "bound replication transcription", "replication transcription complex", "complex rtc", ". the replication", "the replication strategy", "replication strategy of", "strategy of covs", "of covs can", "covs can generate", "can generate both", "generate both single", "both single stranded", "single stranded rna", "rna ssrna", "ssrna and", "and double stranded", "double stranded rna", "rna dsrna", "dsrna species", "species that", "that may act", "may act as", "act as pathogen", "as pathogen associated", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "pamps recognized", "recognized by pattern", "by pattern recognition", "pattern recognition receptor", "receptor prr", "prr such", "such as toll", "as toll like", "toll like receptor", "like receptor 7", "7 tlr7", "tlr8 antiviral", "antiviral innate immune", "innate immune response", "immune response receptor", "response receptor rig", "receptor rig i", "i also", "also known as", "known as dead", "as dead box", "dead box protein", "box protein 58", "58 ddx58", "and interferon induced", "interferon induced helicase", "induced helicase c", "helicase c domain", "c domain containing", "domain containing protein", "containing protein 1", "1 ifih1", "ifih1 also", "known as mda5", "salvi v et", "v et al.", "2021 campbell", "campbell gr et", "gr et al.", "2021 rebendenne", "rebendenne a et", "a et al.", ". the activated", "the activated prrs", "activated prrs trigger", "prrs trigger signaling", "trigger signaling pathways", "signaling pathways to", "pathways to produce", "to produce type", "produce type i", "type i and", "i and type", "and type iii", "type iii interferons", "iii interferons ifns", "interferons ifns and", "ifns and proinflammatory", "and proinflammatory mediators", "proinflammatory mediators that", "mediators that perform", "that perform antiviral", "perform antiviral functions.", "antiviral functions. this", "functions. this reactome", "this reactome module", "reactome module describes", "module describes the", "describes the mechanisms", "the mechanisms underlying", "mechanisms underlying prr", "underlying prr mediated", "prr mediated sensing", "mediated sensing of", "sensing of the", "of the severe", "the severe acute", "severe acute respiratory", "acute respiratory syndrome", "respiratory syndrome coronavirus", "syndrome coronavirus type", "coronavirus type 2", "2 sars", "2 infection.", "first endosomal", "endosomal recognition of", "recognition of viral", "of viral ssrna", "viral ssrna occurs", "ssrna occurs by", "occurs by means", "by means of", "means of tlr7", "of tlr7 and", "tlr7 and tlr8", "tlr8 which", "which detect gu", "detect gu rich", "gu rich ssrna", "rich ssrna sequences", "sequences salvi", "2021 . second", "second sars", "cov 2 dsrna", "2 dsrna replication", "dsrna replication intermediates", "replication intermediates can", "intermediates can be", "can be recognized", "be recognized by", "recognized by cytoplasmic", "by cytoplasmic receptors", "cytoplasmic receptors ddx58", "receptors ddx58 and", "ddx58 and ifih1", "and ifih1 which", "ifih1 which bind", "which bind to", "bind to mitochondrial", "to mitochondrial antiviral", "mitochondrial antiviral signaling", "antiviral signaling protein", "protein mavs", "mavs ips", "1 to", "to induce the", "induce the ifn", "the ifn mediated", "ifn mediated antiviral", "mediated antiviral response", "response rebendenne", "2021 yin", "yin x et", "x et al.", "2021 . in", ". in addition", "addition sars", "cov 2 e", "2 e can", "e can be", "can be sensed", "be sensed by", "sensed by tlr2", "tlr2 zheng", "zheng m et", "m et al.", "2021 . further", "further cellular", "cellular nucleic acid", "nucleic acid binding", "acid binding protein", "protein cnbp", "cnbp and", "and la related", "la related protein", "related protein 1", "1 larp1", "larp1 can", "can directly bind", "directly bind sars", "bind sars cov", "cov 2 grna", "2 grna to", "grna to repress", "to repress sars", "repress sars cov", "cov 2 replication", "replication schmidt", "schmidt n et", "n et al.", "2021 . this", ". this module", "this module also", "module also describes", "also describes several", "describes several strategies", "several strategies developed", "strategies developed by", "developed by sars", "by sars cov", "cov 2 to", "2 to evade", "to evade or", "evade or alter", "or alter host", "alter host immunity", "immunity including", "including escaping innate", "escaping innate immune", "innate immune sensors", "sensors inhibiting", "inhibiting ifn production", "ifn production and", "production and signaling", "signaling and", "and evading antiviral", "evading antiviral function", "antiviral function of", "function of ifn", "of ifn stimulated", "ifn stimulated gene", "gene isg", "isg products.", "products. for example", "example sars", "cov 2 encodes", "2 encodes nsp14", "encodes nsp14 and", "nsp14 and nsp16", "and nsp16 which", "nsp16 which possess", "which possess guanine", "possess guanine n7", "guanine n7 methyltransferase", "n7 methyltransferase activity", "methyltransferase activity and", "activity and 2\u2019", "and 2\u2019 o", "2\u2019 o methyl", "o methyl transferase", "methyl transferase activity", "transferase activity respectively", "respectively ogando", "ogando ns et", "ns et al.", "et al. 2020", "2020 krafcikova", "krafcikova p et", "2020 viswanatha", "viswanatha t et", "t et al.", "2020 lin", "lin s et", "2021 yan", "yan l et", "l et al.", ". in human", "in human coronaviruses", "human coronaviruses nsp14", "coronaviruses nsp14 generates", "nsp14 generates 5'", "generates 5' cap", "5' cap 0", "cap 0 viral", "0 viral rna", "rna m7gpppn", "m7gpppn guanine", "guanine n7 methylated", "methylated and", "and nsp16 further", "nsp16 further methylates", "further methylates cap", "methylates cap 0", "0 viral rna.", "viral rna. these", "rna. these viral", "these viral rna", "viral rna modifications", "rna modifications mimic", "modifications mimic the", "mimic the 5'", "the 5' cap", "5' cap structure", "cap structure of", "structure of host", "of host mrnas", "host mrnas allowing", "mrnas allowing the", "allowing the virus", "the virus to", "virus to efficiently", "to efficiently evade", "efficiently evade recognition", "evade recognition by", "recognition by cytosolic", "by cytosolic ddx58", "cytosolic ddx58 and", "ifih1 chen", "chen y et", "y et al.", "et al. 2009", "2009 2011", "2011 daffis", "daffis s et", "et al. 2010", "2010 shown", "shown for covs", "for covs such", "covs such as", "such as sars", "as sars cov", "sars cov 1", "cov 1 and", "1 and mers", "and mers cov", "mers cov .", "cov . structural", ". structural studies", "structural studies and", "studies and computational", "and computational analysis", "computational analysis suggest", "analysis suggest that", "suggest that properties", "that properties and", "properties and biological", "and biological functions", "biological functions of", "functions of sars", "of sars cov", "cov 2 nsp14", "2 nsp14 and", "and nsp16 could", "nsp16 could be", "could be very", "be very similar", "very similar to", "similar to these", "to these of", "these of sars", "1 rosas", "rosas lemus m", "lemus m et", "2020 viswanathan", "viswanathan t et", "2020 jiang", "jiang y et", "2020 wilamowski", "wilamowski m et", "further the", "the uridylate\u2010specific endoribonuclease", "endoribonuclease endou", "endou activity", "activity of sars", "cov 2 nsp15", "2 nsp15 degrades", "nsp15 degrades viral", "degrades viral rna", "viral rna to", "rna to hide", "to hide it", "hide it from", "it from innate", "from innate immune", "sensors frazier", "frazier mn et", "mn et al.", "2021 . moreover", "moreover sars", "2 encodes several", "encodes several proteins", "several proteins that", "proteins that directly", "that directly bind", "directly bind to", "bind to host", "to host targets", "host targets associated", "targets associated with", "associated with sars\u2011cov\u20112", "with sars\u2011cov\u20112 infection", "sars\u2011cov\u20112 infection and", "infection and cytokine", "and cytokine production", "production shin", "shin d et", "d et al.", "2020 xia", "xia h et", "h et al.", "2020 matsuyama", "matsuyama t et", "2020 yuen", "yuen ck et", "ck et al.", "2020 reviewed", "reviewed by park", "by park a", "park a &", "a & iwasaki", "& iwasaki a", "iwasaki a 2020", "a 2020 .", "2020 . this", ". this reactome", "module describes several", "describes several such", "several such binding", "such binding events", "binding events and", "events and their", "and their consequences.", "their consequences. for", "consequences. for example", "example as", "as a deubiquitinating", "a deubiquitinating and", "deubiquitinating and deisgylating", "and deisgylating enzyme", "enzyme viral", "viral nsp3 binds", "nsp3 binds to", "binds to and", "to and removes", "and removes isg15", "removes isg15 from", "isg15 from signaling", "from signaling proteins", "signaling proteins such", "proteins such as", "such as irf3", "as irf3 and", "irf3 and ifih1", "and ifih1 thereby", "ifih1 thereby modulating", "thereby modulating the", "modulating the formation", "the formation of", "formation of signaling", "of signaling complexes", "signaling complexes and", "complexes and the", "and the activation", "the activation of", "activation of irf3/7", "of irf3/7 and", "irf3/7 and nf", "and nf kappab", "kappab liu", "liu cq et", "cq et al.", "2021 . binding", ". binding of", "binding of sars", "cov 2 nsp6", "nsp6 nsp13", "nsp13 or membrane", "membrane m", "protein to cytosolic", "to cytosolic tbk1", "cytosolic tbk1 prevents", "tbk1 prevents irf3/7", "prevents irf3/7 activation", "irf3/7 activation and", "activation and inhibits", "and inhibits ifn", "inhibits ifn production", "ifn production downstream", "production downstream of", "downstream of ddx58", "ddx58 ifih1", "ifih1 mavs", "mavs and sting", "and sting signaling", "sting signaling pathways", "pathways xia", "2020 sui", "sui l et", "2021 . next", "next m", "m protein targets", "protein targets mavs", "targets mavs to", "mavs to prevent", "to prevent the", "prevent the formation", "formation of the", "of the mavs", "the mavs signalosome", "mavs signalosome complex", "signalosome complex and", "complex and thereby", "and thereby inhibits", "thereby inhibits downstream", "inhibits downstream signaling", "downstream signaling pathways", "signaling pathways of", "pathways of ddx58", "of ddx58 and", "ifih1 fu", "fu yz et", "yz et al.", "cov 2 nucleocapsid", "nucleocapsid n", "n protein", "protein to e3", "to e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase trim25", "ligase trim25 inhibits", "trim25 inhibits trim25", "inhibits trim25 mediated", "trim25 mediated ddx58", "mediated ddx58 ubiquitination", "ddx58 ubiquitination and", "ubiquitination and the", "and the ddx58", "the ddx58 signaling", "ddx58 signaling pathway", "pathway gori", "gori sg et", "sg et al.", "2021 . n", ". n interacts", "n interacts with", "interacts with nlrp3", "with nlrp3 to", "nlrp3 to promote", "to promote the", "promote the assembly", "the assembly and", "assembly and activation", "and activation of", "activation of the", "of the nlrp3", "the nlrp3 inflammasome", "inflammasome pan", "pan p et", ". the interaction", "the interaction between", "interaction between viral", "between viral n", "viral n and", "n and masp2", "and masp2 promotes", "masp2 promotes masp2", "promotes masp2 mediated", "masp2 mediated cleavage", "mediated cleavage of", "cleavage of c4", "c4 ali", "ali ym et", "ym et al.", "2021 and", "c2 kang", "kang s et", "2021 leading", "leading to the", "to the hyperactivation", "the hyperactivation of", "hyperactivation of the", "of the complement", "the complement system.", "complement system. besides", "besides viral", "viral n promotes", "n promotes nf", "promotes nf kappab", "nf kappab activation", "kappab activation by", "activation by targeting", "by targeting signaling", "targeting signaling complexes", "signaling complexes of", "complexes of tak1", "of tak1 and", "tak1 and ikk", "ikk wu", "wu y et", ". the ion", "the ion channel", "ion channel activities", "channel activities of", "activities of accessory", "of accessory protein", "accessory protein orf3a", "protein orf3a or", "orf3a or 3a", "3a open", "open reading frame", "reading frame 3a", "3a and", "and sars\u2011cov\u20112 envelope", "envelope e", "e protein", "protein contribute to", "contribute to activation", "to activation of", "nlrp3 inflammasome leading", "inflammasome leading to", "leading to highly", "to highly inflammatory", "highly inflammatory pyroptotic", "inflammatory pyroptotic cell", "pyroptotic cell death", "death based", "based on findings", "on findings for", "findings for sars", "for sars cov", "1 siu", "siu kl et", "kl et al.", "et al. 2019", "al. 2019 .", "2019 . sars", ". sars cov", "cov 2 nsp5", "2 nsp5 protease", "protease 3clpro", "3clpro cleaves", "tab1 a", "a component of", "component of the", "of the tak1", "the tak1 complex", "complex thus", "thus inhibiting nf", "inhibiting nf kappab", "activation moustaqil", "moustaqil m et", "m et al", "et al .2021", "al .2021 .", ".2021 . 3clpro", ". 3clpro targets", "3clpro targets nlrp12", "targets nlrp12 which", "nlrp12 which modulates", "which modulates the", "modulates the expression", "the expression of", "expression of inflammatory", "of inflammatory cytokines", "inflammatory cytokines through", "cytokines through the", "through the regulation", "the regulation of", "regulation of the", "of the nfkappab", "the nfkappab and", "nfkappab and mapk", "and mapk pathways", "pathways moustaqil", "2021 . sars", "cov 2 6", "6 orf6", "orf6 interacts", "interacts with importin", "with importin kpna2", "importin kpna2 and", "kpna2 and components", "and components of", "components of the", "of the nuclear", "the nuclear pore", "nuclear pore complex", "complex nup98", "nup98 and rae1", "rae1 to", "to block nuclear", "block nuclear translocation", "nuclear translocation of", "translocation of irf3", "irf3 stat1", "stat1 and stat2", "stat2 xia", "2020 miorin", "miorin l et", "al. 2020 .", "2020 . sars", "cov 2 9b", "9b orf9b", "orf9b inhibits", "inhibits the mavs", "the mavs mediated", "mavs mediated production", "mediated production of", "production of type", "of type i", "type i ifns", "i ifns by", "ifns by targeting", "by targeting tomm70", "targeting tomm70 on", "tomm70 on the", "on the mitochondria", "mitochondria jiang", "jiang hw et", "hw et al.", "2020 . binding", "binding of mitochondrial", "of mitochondrial viral", "mitochondrial viral 9", "viral 9 to", "9 to ikbkg", "to ikbkg prevents", "ikbkg prevents mavs", "prevents mavs dependent", "mavs dependent nf", "dependent nf kappab", "activation wu", "wu j et", "j et al.", "2021 . although", ". although the", "although the evasion", "the evasion mechanisms", "evasion mechanisms are", "mechanisms are mainly", "are mainly conserved", "mainly conserved between", "conserved between sars", "between sars cov", "1 and sars", "and sars cov", "2 gordon", "gordon de et", "de et al.", "studies identified sars", "identified sars cov", "cov 2 specific", "2 specific modulations", "specific modulations of", "modulations of host", "of host immune", "host immune response", "immune response that", "response that may", "that may contribute", "may contribute to", "contribute to pathophysiological", "to pathophysiological determinants", "pathophysiological determinants of", "determinants of covid", "of covid 19", "19 gordon", "2020 schiller", "schiller hb et", "hb et al.", "describes several virus", "several virus host", "virus host interactions", "host interactions identified", "interactions identified in", "identified in cells", "in cells during", "cells during sars", "during sars cov", "2 but", "but not sars", "not sars cov", "1 infection.", "infection. for example", "cov 2 8", "8 orf8", "orf8 regulates", "regulates the expression", "expression of class", "of class i", "class i mhc", "i mhc on", "mhc on the", "on the surface", "the surface of", "surface of the", "of the infected", "the infected cells", "infected cells through", "cells through an", "through an autophagy", "an autophagy dependent", "autophagy dependent lysosomal", "dependent lysosomal degradation", "lysosomal degradation of", "degradation of class", "mhc zhang", "zhang y et", "2021 . at", ". at the", "at the plasma", "the plasma membrane", "membrane binding", "binding of secreted", "of secreted viral", "secreted viral 8", "viral 8 to", "8 to il17ra", "to il17ra activates", "il17ra activates il17", "activates il17 signaling", "il17 signaling pathway", "signaling pathway leading", "pathway leading to", "leading to an", "to an increased", "an increased secretion", "increased secretion of", "secretion of cytokines/chemokines", "of cytokines/chemokines thus", "cytokines/chemokines thus contributing", "thus contributing to", "contributing to cytokine", "to cytokine storm", "cytokine storm during", "storm during sars", "cov 2 infection", "infection lin", "lin x et", "2021 . furthermore", "furthermore sars", "cov 2 host", "2 host interactome", "host interactome and", "interactome and proteomics", "and proteomics studies", "proteomics studies identified", "studies identified various", "identified various human", "various human proteins", "human proteins that", "proteins that are", "that are targeted", "are targeted by", "targeted by sars", "cov 2 proteins", "proteins gordon", "et al. 2020a", "2020a b", "b bojkova", "bojkova d et", "2020 stukalov", "stukalov a et", "2021 li", "li j et", "2021 messina", "messina f et", "f et al.", "reactome module does", "module does not", "does not cover", "not cover all", "cover all identified", "all identified sars", "sars cov 2\u2013human", "cov 2\u2013human interactions", "interactions the", "the module describes", "module describes those", "describes those associations", "those associations that", "associations that were", "that were functionally", "were functionally validated.", "covs are positive", "are positive sense rna", "positive sense rna viruses", "sense rna viruses that", "rna viruses that replicate", "viruses that replicate in", "that replicate in the", "replicate in the interior", "in the interior of", "the interior of double", "interior of double membrane", "of double membrane vesicles", "membrane vesicles dmv", "dmv in the", "in the cytoplasm of", "the cytoplasm of infected", "cytoplasm of infected cells", "infected cells stertz", "cells stertz s", "stertz s et al.", "s et al. 2007", "al. 2007 knoops", "2007 knoops k", "knoops k et al.", "k et al. 2008", "al. 2008 v'kovski", "2008 v'kovski p", "v'kovski p et al.", "p et al. 2021", "et al. 2021 .", "al. 2021 . the", "2021 . the viral", ". the viral replication", "the viral replication and", "viral replication and transcription", "replication and transcription are", "and transcription are facilitated", "transcription are facilitated by", "are facilitated by virus", "facilitated by virus encoded", "by virus encoded non", "virus encoded non structural", "encoded non structural proteins", "structural proteins sars", "proteins sars cov", "sars cov 2 nsp1\u2013nsp16", "2 nsp1\u2013nsp16 that", "nsp1\u2013nsp16 that assemble", "that assemble to form", "assemble to form a", "to form a dmv", "form a dmv bound", "a dmv bound replication", "dmv bound replication transcription", "bound replication transcription complex", "transcription complex rtc", "rtc v'kovski", "2021 . the replication", ". the replication strategy", "the replication strategy of", "replication strategy of covs", "strategy of covs can", "of covs can generate", "covs can generate both", "can generate both single", "generate both single stranded", "both single stranded rna", "stranded rna ssrna", "ssrna and double", "and double stranded rna", "stranded rna dsrna", "species that may", "that may act as", "may act as pathogen", "act as pathogen associated", "as pathogen associated molecular", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps recognized by", "recognized by pattern recognition", "by pattern recognition receptor", "recognition receptor prr", "prr such as", "such as toll like", "as toll like receptor", "toll like receptor 7", "receptor 7 tlr7", "and tlr8 antiviral", "tlr8 antiviral innate", "antiviral innate immune response", "innate immune response receptor", "immune response receptor rig", "response receptor rig i", "rig i also", "i also known", "also known as dead", "known as dead box", "as dead box protein", "dead box protein 58", "protein 58 ddx58", "ddx58 and interferon", "and interferon induced helicase", "interferon induced helicase c", "induced helicase c domain", "helicase c domain containing", "c domain containing protein", "domain containing protein 1", "protein 1 ifih1", "ifih1 also known", "also known as mda5", "mda5 salvi", "salvi v et al.", "v et al. 2021", "al. 2021 campbell", "2021 campbell gr", "campbell gr et al.", "gr et al. 2021", "al. 2021 rebendenne", "2021 rebendenne a", "rebendenne a et al.", "a et al. 2021", "2021 . the activated", ". the activated prrs", "the activated prrs trigger", "activated prrs trigger signaling", "prrs trigger signaling pathways", "trigger signaling pathways to", "signaling pathways to produce", "pathways to produce type", "to produce type i", "produce type i and", "type i and type", "i and type iii", "and type iii interferons", "type iii interferons ifns", "iii interferons ifns and", "interferons ifns and proinflammatory", "ifns and proinflammatory mediators", "and proinflammatory mediators that", "proinflammatory mediators that perform", "mediators that perform antiviral", "that perform antiviral functions.", "perform antiviral functions. this", "antiviral functions. this reactome", "functions. this reactome module", "this reactome module describes", "reactome module describes the", "module describes the mechanisms", "describes the mechanisms underlying", "the mechanisms underlying prr", "mechanisms underlying prr mediated", "underlying prr mediated sensing", "prr mediated sensing of", "mediated sensing of the", "sensing of the severe", "of the severe acute", "the severe acute respiratory", "severe acute respiratory syndrome", "acute respiratory syndrome coronavirus", "respiratory syndrome coronavirus type", "syndrome coronavirus type 2", "type 2 sars", "2 sars cov", "cov 2 infection.", "2 infection. first", "infection. first endosomal", "first endosomal recognition", "endosomal recognition of viral", "recognition of viral ssrna", "of viral ssrna occurs", "viral ssrna occurs by", "ssrna occurs by means", "occurs by means of", "by means of tlr7", "means of tlr7 and", "of tlr7 and tlr8", "and tlr8 which", "tlr8 which detect", "which detect gu rich", "detect gu rich ssrna", "gu rich ssrna sequences", "ssrna sequences salvi", "sequences salvi v", "al. 2021 . second", ". second sars", "second sars cov", "sars cov 2 dsrna", "cov 2 dsrna replication", "2 dsrna replication intermediates", "dsrna replication intermediates can", "replication intermediates can be", "intermediates can be recognized", "can be recognized by", "be recognized by cytoplasmic", "recognized by cytoplasmic receptors", "by cytoplasmic receptors ddx58", "cytoplasmic receptors ddx58 and", "receptors ddx58 and ifih1", "ddx58 and ifih1 which", "and ifih1 which bind", "ifih1 which bind to", "which bind to mitochondrial", "bind to mitochondrial antiviral", "to mitochondrial antiviral signaling", "mitochondrial antiviral signaling protein", "signaling protein mavs", "mavs ips 1", "ips 1 to", "1 to induce", "to induce the ifn", "induce the ifn mediated", "the ifn mediated antiviral", "ifn mediated antiviral response", "antiviral response rebendenne", "response rebendenne a", "al. 2021 yin", "2021 yin x", "yin x et al.", "x et al. 2021", "al. 2021 . in", "2021 . in addition", "in addition sars", "addition sars cov", "sars cov 2 e", "cov 2 e can", "2 e can be", "e can be sensed", "can be sensed by", "be sensed by tlr2", "by tlr2 zheng", "tlr2 zheng m", "zheng m et al.", "m et al. 2021", "al. 2021 . further", ". further cellular", "further cellular nucleic", "cellular nucleic acid binding", "nucleic acid binding protein", "binding protein cnbp", "cnbp and la", "and la related protein", "la related protein 1", "protein 1 larp1", "larp1 can directly", "can directly bind sars", "directly bind sars cov", "bind sars cov 2", "sars cov 2 grna", "cov 2 grna to", "2 grna to repress", "grna to repress sars", "to repress sars cov", "repress sars cov 2", "sars cov 2 replication", "2 replication schmidt", "replication schmidt n", "schmidt n et al.", "n et al. 2021", "al. 2021 . this", "2021 . this module", ". this module also", "this module also describes", "module also describes several", "also describes several strategies", "describes several strategies developed", "several strategies developed by", "strategies developed by sars", "developed by sars cov", "by sars cov 2", "sars cov 2 to", "cov 2 to evade", "2 to evade or", "to evade or alter", "evade or alter host", "or alter host immunity", "host immunity including", "immunity including escaping", "including escaping innate immune", "escaping innate immune sensors", "immune sensors inhibiting", "sensors inhibiting ifn", "inhibiting ifn production and", "ifn production and signaling", "and signaling and", "signaling and evading", "and evading antiviral function", "evading antiviral function of", "antiviral function of ifn", "function of ifn stimulated", "of ifn stimulated gene", "stimulated gene isg", "isg products. for", "for example sars", "example sars cov", "sars cov 2 encodes", "cov 2 encodes nsp14", "2 encodes nsp14 and", "encodes nsp14 and nsp16", "nsp14 and nsp16 which", "and nsp16 which possess", "nsp16 which possess guanine", "which possess guanine n7", "possess guanine n7 methyltransferase", "guanine n7 methyltransferase activity", "n7 methyltransferase activity and", "methyltransferase activity and 2\u2019", "activity and 2\u2019 o", "and 2\u2019 o methyl", "2\u2019 o methyl transferase", "o methyl transferase activity", "methyl transferase activity respectively", "activity respectively ogando", "respectively ogando ns", "ogando ns et al.", "ns et al. 2020", "al. 2020 krafcikova", "2020 krafcikova p", "krafcikova p et al.", "p et al. 2020", "al. 2020 viswanatha", "2020 viswanatha t", "viswanatha t et al.", "t et al. 2020", "al. 2020 lin", "2020 lin s", "lin s et al.", "s et al. 2021", "al. 2021 yan", "2021 yan l", "yan l et al.", "l et al. 2021", "2021 . in human", ". in human coronaviruses", "in human coronaviruses nsp14", "human coronaviruses nsp14 generates", "coronaviruses nsp14 generates 5'", "nsp14 generates 5' cap", "generates 5' cap 0", "5' cap 0 viral", "cap 0 viral rna", "viral rna m7gpppn", "m7gpppn guanine n7", "n7 methylated and", "methylated and nsp16", "and nsp16 further methylates", "nsp16 further methylates cap", "further methylates cap 0", "methylates cap 0 viral", "cap 0 viral rna.", "0 viral rna. these", "viral rna. these viral", "rna. these viral rna", "these viral rna modifications", "viral rna modifications mimic", "rna modifications mimic the", "modifications mimic the 5'", "mimic the 5' cap", "the 5' cap structure", "5' cap structure of", "cap structure of host", "structure of host mrnas", "of host mrnas allowing", "host mrnas allowing the", "mrnas allowing the virus", "allowing the virus to", "the virus to efficiently", "virus to efficiently evade", "to efficiently evade recognition", "efficiently evade recognition by", "evade recognition by cytosolic", "recognition by cytosolic ddx58", "by cytosolic ddx58 and", "cytosolic ddx58 and ifih1", "and ifih1 chen", "ifih1 chen y", "chen y et al.", "y et al. 2009", "al. 2009 2011", "2011 daffis s", "daffis s et al.", "s et al. 2010", "al. 2010 shown", "2010 shown for", "shown for covs such", "for covs such as", "covs such as sars", "such as sars cov", "as sars cov 1", "sars cov 1 and", "cov 1 and mers", "1 and mers cov", "and mers cov .", "mers cov . structural", "cov . structural studies", ". structural studies and", "structural studies and computational", "studies and computational analysis", "and computational analysis suggest", "computational analysis suggest that", "analysis suggest that properties", "suggest that properties and", "that properties and biological", "properties and biological functions", "and biological functions of", "biological functions of sars", "functions of sars cov", "of sars cov 2", "sars cov 2 nsp14", "cov 2 nsp14 and", "2 nsp14 and nsp16", "nsp14 and nsp16 could", "and nsp16 could be", "nsp16 could be very", "could be very similar", "be very similar to", "very similar to these", "similar to these of", "to these of sars", "these of sars cov", "of sars cov 1", "cov 1 rosas", "1 rosas lemus", "rosas lemus m et", "lemus m et al.", "m et al. 2020", "s et al. 2020", "al. 2020 viswanathan", "2020 viswanathan t", "viswanathan t et al.", "al. 2020 jiang", "2020 jiang y", "jiang y et al.", "y et al. 2020", "al. 2020 wilamowski", "2020 wilamowski m", "wilamowski m et al.", ". further the", "further the uridylate\u2010specific", "uridylate\u2010specific endoribonuclease endou", "endou activity of", "activity of sars cov", "sars cov 2 nsp15", "cov 2 nsp15 degrades", "2 nsp15 degrades viral", "nsp15 degrades viral rna", "degrades viral rna to", "viral rna to hide", "rna to hide it", "to hide it from", "hide it from innate", "it from innate immune", "from innate immune sensors", "immune sensors frazier", "sensors frazier mn", "frazier mn et al.", "mn et al. 2021", "al. 2021 . moreover", ". moreover sars", "moreover sars cov", "cov 2 encodes several", "2 encodes several proteins", "encodes several proteins that", "several proteins that directly", "proteins that directly bind", "that directly bind to", "directly bind to host", "bind to host targets", "to host targets associated", "host targets associated with", "targets associated with sars\u2011cov\u20112", "associated with sars\u2011cov\u20112 infection", "with sars\u2011cov\u20112 infection and", "sars\u2011cov\u20112 infection and cytokine", "infection and cytokine production", "cytokine production shin", "production shin d", "shin d et al.", "d et al. 2020", "al. 2020 xia", "2020 xia h", "xia h et al.", "h et al. 2020", "al. 2020 matsuyama", "2020 matsuyama t", "matsuyama t et al.", "al. 2020 yuen", "2020 yuen ck", "yuen ck et al.", "ck et al. 2020", "al. 2020 reviewed", "2020 reviewed by", "reviewed by park a", "by park a &", "park a & iwasaki", "a & iwasaki a", "& iwasaki a 2020", "iwasaki a 2020 .", "a 2020 . this", "2020 . this reactome", ". this reactome module", "reactome module describes several", "module describes several such", "describes several such binding", "several such binding events", "such binding events and", "binding events and their", "events and their consequences.", "and their consequences. for", "their consequences. for example", "for example as", "example as a", "as a deubiquitinating and", "a deubiquitinating and deisgylating", "deubiquitinating and deisgylating enzyme", "deisgylating enzyme viral", "enzyme viral nsp3", "viral nsp3 binds to", "nsp3 binds to and", "binds to and removes", "to and removes isg15", "and removes isg15 from", "removes isg15 from signaling", "isg15 from signaling proteins", "from signaling proteins such", "signaling proteins such as", "proteins such as irf3", "such as irf3 and", "as irf3 and ifih1", "irf3 and ifih1 thereby", "and ifih1 thereby modulating", "ifih1 thereby modulating the", "thereby modulating the formation", "modulating the formation of", "the formation of signaling", "formation of signaling complexes", "of signaling complexes and", "signaling complexes and the", "complexes and the activation", "and the activation of", "the activation of irf3/7", "activation of irf3/7 and", "of irf3/7 and nf", "irf3/7 and nf kappab", "nf kappab liu", "kappab liu cq", "liu cq et al.", "cq et al. 2021", "al. 2021 . binding", "2021 . binding of", ". binding of sars", "binding of sars cov", "sars cov 2 nsp6", "2 nsp6 nsp13", "nsp6 nsp13 or", "or membrane m", "m protein to", "protein to cytosolic tbk1", "to cytosolic tbk1 prevents", "cytosolic tbk1 prevents irf3/7", "tbk1 prevents irf3/7 activation", "prevents irf3/7 activation and", "irf3/7 activation and inhibits", "activation and inhibits ifn", "and inhibits ifn production", "inhibits ifn production downstream", "ifn production downstream of", "production downstream of ddx58", "of ddx58 ifih1", "ifih1 mavs and", "mavs and sting signaling", "and sting signaling pathways", "signaling pathways xia", "pathways xia h", "al. 2020 sui", "2020 sui l", "sui l et al.", "al. 2021 . next", ". next m", "next m protein", "m protein targets mavs", "protein targets mavs to", "targets mavs to prevent", "mavs to prevent the", "to prevent the formation", "prevent the formation of", "the formation of the", "formation of the mavs", "of the mavs signalosome", "the mavs signalosome complex", "mavs signalosome complex and", "signalosome complex and thereby", "complex and thereby inhibits", "and thereby inhibits downstream", "thereby inhibits downstream signaling", "inhibits downstream signaling pathways", "downstream signaling pathways of", "signaling pathways of ddx58", "pathways of ddx58 and", "of ddx58 and ifih1", "and ifih1 fu", "ifih1 fu yz", "fu yz et al.", "yz et al. 2021", "sars cov 2 nucleocapsid", "2 nucleocapsid n", "n protein to", "protein to e3 ubiquitin", "to e3 ubiquitin ligase", "e3 ubiquitin ligase trim25", "ubiquitin ligase trim25 inhibits", "ligase trim25 inhibits trim25", "trim25 inhibits trim25 mediated", "inhibits trim25 mediated ddx58", "trim25 mediated ddx58 ubiquitination", "mediated ddx58 ubiquitination and", "ddx58 ubiquitination and the", "ubiquitination and the ddx58", "and the ddx58 signaling", "the ddx58 signaling pathway", "signaling pathway gori", "pathway gori sg", "gori sg et al.", "sg et al. 2021", "al. 2021 . n", "2021 . n interacts", ". n interacts with", "n interacts with nlrp3", "interacts with nlrp3 to", "with nlrp3 to promote", "nlrp3 to promote the", "to promote the assembly", "promote the assembly and", "the assembly and activation", "assembly and activation of", "and activation of the", "activation of the nlrp3", "of the nlrp3 inflammasome", "nlrp3 inflammasome pan", "inflammasome pan p", "pan p et al.", "2021 . the interaction", ". the interaction between", "the interaction between viral", "interaction between viral n", "between viral n and", "viral n and masp2", "n and masp2 promotes", "and masp2 promotes masp2", "masp2 promotes masp2 mediated", "promotes masp2 mediated cleavage", "masp2 mediated cleavage of", "mediated cleavage of c4", "of c4 ali", "c4 ali ym", "ali ym et al.", "ym et al. 2021", "al. 2021 and", "2021 and c2", "and c2 kang", "c2 kang s", "kang s et al.", "al. 2021 leading", "2021 leading to", "leading to the hyperactivation", "to the hyperactivation of", "the hyperactivation of the", "hyperactivation of the complement", "of the complement system.", "the complement system. besides", "system. besides viral", "besides viral n", "viral n promotes nf", "n promotes nf kappab", "promotes nf kappab activation", "nf kappab activation by", "kappab activation by targeting", "activation by targeting signaling", "by targeting signaling complexes", "targeting signaling complexes of", "signaling complexes of tak1", "complexes of tak1 and", "of tak1 and ikk", "and ikk wu", "ikk wu y", "wu y et al.", "y et al. 2021", "2021 . the ion", ". the ion channel", "the ion channel activities", "ion channel activities of", "channel activities of accessory", "activities of accessory protein", "of accessory protein orf3a", "accessory protein orf3a or", "protein orf3a or 3a", "or 3a open", "3a open reading", "open reading frame 3a", "frame 3a and", "3a and sars\u2011cov\u20112", "sars\u2011cov\u20112 envelope e", "e protein contribute", "protein contribute to activation", "contribute to activation of", "to activation of the", "the nlrp3 inflammasome leading", "nlrp3 inflammasome leading to", "inflammasome leading to highly", "leading to highly inflammatory", "to highly inflammatory pyroptotic", "highly inflammatory pyroptotic cell", "inflammatory pyroptotic cell death", "cell death based", "death based on", "based on findings for", "on findings for sars", "findings for sars cov", "for sars cov 1", "cov 1 siu", "1 siu kl", "siu kl et al.", "kl et al. 2019", "et al. 2019 .", "al. 2019 . sars", "2019 . sars cov", ". sars cov 2", "sars cov 2 nsp5", "cov 2 nsp5 protease", "nsp5 protease 3clpro", "3clpro cleaves tab1", "cleaves tab1 a", "tab1 a component", "a component of the", "component of the tak1", "of the tak1 complex", "tak1 complex thus", "complex thus inhibiting", "thus inhibiting nf kappab", "inhibiting nf kappab activation", "kappab activation moustaqil", "activation moustaqil m", "moustaqil m et al", "m et al .2021", "et al .2021 .", "al .2021 . 3clpro", ".2021 . 3clpro targets", ". 3clpro targets nlrp12", "3clpro targets nlrp12 which", "targets nlrp12 which modulates", "nlrp12 which modulates the", "which modulates the expression", "modulates the expression of", "the expression of inflammatory", "expression of inflammatory cytokines", "of inflammatory cytokines through", "inflammatory cytokines through the", "cytokines through the regulation", "through the regulation of", "the regulation of the", "regulation of the nfkappab", "of the nfkappab and", "the nfkappab and mapk", "nfkappab and mapk pathways", "mapk pathways moustaqil", "pathways moustaqil m", "moustaqil m et al.", "al. 2021 . sars", "2021 . sars cov", "sars cov 2 6", "2 6 orf6", "orf6 interacts with", "interacts with importin kpna2", "with importin kpna2 and", "importin kpna2 and components", "kpna2 and components of", "and components of the", "components of the nuclear", "of the nuclear pore", "the nuclear pore complex", "pore complex nup98", "complex nup98 and", "and rae1 to", "rae1 to block", "to block nuclear translocation", "block nuclear translocation of", "nuclear translocation of irf3", "of irf3 stat1", "irf3 stat1 and", "and stat2 xia", "stat2 xia h", "al. 2020 miorin", "2020 miorin l", "miorin l et al.", "l et al. 2020", "et al. 2020 .", "al. 2020 . sars", "2020 . sars cov", "sars cov 2 9b", "2 9b orf9b", "orf9b inhibits the", "inhibits the mavs mediated", "the mavs mediated production", "mavs mediated production of", "mediated production of type", "production of type i", "of type i ifns", "type i ifns by", "i ifns by targeting", "ifns by targeting tomm70", "by targeting tomm70 on", "targeting tomm70 on the", "tomm70 on the mitochondria", "the mitochondria jiang", "mitochondria jiang hw", "jiang hw et al.", "hw et al. 2020", "al. 2020 . binding", "2020 . binding of", ". binding of mitochondrial", "binding of mitochondrial viral", "of mitochondrial viral 9", "mitochondrial viral 9 to", "viral 9 to ikbkg", "9 to ikbkg prevents", "to ikbkg prevents mavs", "ikbkg prevents mavs dependent", "prevents mavs dependent nf", "mavs dependent nf kappab", "dependent nf kappab activation", "kappab activation wu", "activation wu j", "wu j et al.", "j et al. 2021", "al. 2021 . although", "2021 . although the", ". although the evasion", "although the evasion mechanisms", "the evasion mechanisms are", "evasion mechanisms are mainly", "mechanisms are mainly conserved", "are mainly conserved between", "mainly conserved between sars", "conserved between sars cov", "between sars cov 1", "cov 1 and sars", "1 and sars cov", "and sars cov 2", "cov 2 gordon", "2 gordon de", "gordon de et al.", "de et al. 2020", "2020 studies", "studies identified sars cov", "identified sars cov 2", "sars cov 2 specific", "cov 2 specific modulations", "2 specific modulations of", "specific modulations of host", "modulations of host immune", "of host immune response", "host immune response that", "immune response that may", "response that may contribute", "that may contribute to", "may contribute to pathophysiological", "contribute to pathophysiological determinants", "to pathophysiological determinants of", "pathophysiological determinants of covid", "determinants of covid 19", "covid 19 gordon", "19 gordon de", "al. 2020 schiller", "2020 schiller hb", "schiller hb et al.", "hb et al. 2021", "2021 . this reactome", "module describes several virus", "describes several virus host", "several virus host interactions", "virus host interactions identified", "host interactions identified in", "interactions identified in cells", "identified in cells during", "in cells during sars", "cells during sars cov", "during sars cov 2", "cov 2 but", "2 but not", "but not sars cov", "not sars cov 1", "cov 1 infection.", "1 infection. for", "sars cov 2 8", "2 8 orf8", "orf8 regulates the", "regulates the expression of", "the expression of class", "expression of class i", "of class i mhc", "class i mhc on", "i mhc on the", "mhc on the surface", "on the surface of", "the surface of the", "surface of the infected", "of the infected cells", "the infected cells through", "infected cells through an", "cells through an autophagy", "through an autophagy dependent", "an autophagy dependent lysosomal", "autophagy dependent lysosomal degradation", "dependent lysosomal degradation of", "lysosomal degradation of class", "degradation of class i", "i mhc zhang", "mhc zhang y", "zhang y et al.", "al. 2021 . at", "2021 . at the", ". at the plasma", "at the plasma membrane", "plasma membrane binding", "membrane binding of", "binding of secreted viral", "of secreted viral 8", "secreted viral 8 to", "viral 8 to il17ra", "8 to il17ra activates", "to il17ra activates il17", "il17ra activates il17 signaling", "activates il17 signaling pathway", "il17 signaling pathway leading", "signaling pathway leading to", "pathway leading to an", "leading to an increased", "to an increased secretion", "an increased secretion of", "increased secretion of cytokines/chemokines", "secretion of cytokines/chemokines thus", "of cytokines/chemokines thus contributing", "cytokines/chemokines thus contributing to", "thus contributing to cytokine", "contributing to cytokine storm", "to cytokine storm during", "cytokine storm during sars", "storm during sars cov", "sars cov 2 infection", "2 infection lin", "infection lin x", "lin x et al.", "al. 2021 . furthermore", ". furthermore sars", "furthermore sars cov", "sars cov 2 host", "cov 2 host interactome", "2 host interactome and", "host interactome and proteomics", "interactome and proteomics studies", "and proteomics studies identified", "proteomics studies identified various", "studies identified various human", "identified various human proteins", "various human proteins that", "human proteins that are", "proteins that are targeted", "that are targeted by", "are targeted by sars", "targeted by sars cov", "sars cov 2 proteins", "2 proteins gordon", "proteins gordon de", "de et al. 2020a", "al. 2020a b", "b bojkova d", "bojkova d et al.", "al. 2020 stukalov", "2020 stukalov a", "stukalov a et al.", "al. 2021 li", "2021 li j", "li j et al.", "al. 2021 messina", "2021 messina f", "messina f et al.", "f et al. 2021", "this reactome module does", "reactome module does not", "module does not cover", "does not cover all", "not cover all identified", "cover all identified sars", "all identified sars cov", "identified sars cov 2\u2013human", "sars cov 2\u2013human interactions", "2\u2013human interactions the", "interactions the module", "the module describes those", "module describes those associations", "describes those associations that", "those associations that were", "associations that were functionally", "that were functionally validated.", "coronaviruses covs are", "covs are positive sense", "are positive sense rna viruses", "positive sense rna viruses that", "sense rna viruses that replicate", "rna viruses that replicate in", "viruses that replicate in the", "that replicate in the interior", "replicate in the interior of", "in the interior of double", "the interior of double membrane", "interior of double membrane vesicles", "double membrane vesicles dmv", "vesicles dmv in", "dmv in the cytoplasm", "in the cytoplasm of infected", "the cytoplasm of infected cells", "of infected cells stertz", "infected cells stertz s", "cells stertz s et", "stertz s et al. 2007", "et al. 2007 knoops", "al. 2007 knoops k", "2007 knoops k et", "knoops k et al. 2008", "et al. 2008 v'kovski", "al. 2008 v'kovski p", "2008 v'kovski p et", "v'kovski p et al. 2021", "p et al. 2021 .", "et al. 2021 . the", "al. 2021 . the viral", "2021 . the viral replication", ". the viral replication and", "the viral replication and transcription", "viral replication and transcription are", "replication and transcription are facilitated", "and transcription are facilitated by", "transcription are facilitated by virus", "are facilitated by virus encoded", "facilitated by virus encoded non", "by virus encoded non structural", "virus encoded non structural proteins", "non structural proteins sars", "structural proteins sars cov", "proteins sars cov 2", "cov 2 nsp1\u2013nsp16 that", "2 nsp1\u2013nsp16 that assemble", "nsp1\u2013nsp16 that assemble to", "that assemble to form a", "assemble to form a dmv", "to form a dmv bound", "form a dmv bound replication", "a dmv bound replication transcription", "dmv bound replication transcription complex", "replication transcription complex rtc", "rtc v'kovski p", "al. 2021 . the replication", "2021 . the replication strategy", ". the replication strategy of", "the replication strategy of covs", "replication strategy of covs can", "strategy of covs can generate", "of covs can generate both", "covs can generate both single", "can generate both single stranded", "generate both single stranded rna", "single stranded rna ssrna", "rna ssrna and", "ssrna and double stranded", "double stranded rna dsrna", "rna dsrna species", "dsrna species that", "species that may act", "that may act as pathogen", "may act as pathogen associated", "act as pathogen associated molecular", "as pathogen associated molecular patterns", "associated molecular patterns pamps", "patterns pamps recognized", "pamps recognized by pattern", "recognized by pattern recognition receptor", "pattern recognition receptor prr", "receptor prr such", "prr such as toll", "such as toll like receptor", "as toll like receptor 7", "like receptor 7 tlr7", "7 tlr7 and", "and tlr8 antiviral innate", "tlr8 antiviral innate immune", "antiviral innate immune response receptor", "innate immune response receptor rig", "immune response receptor rig i", "receptor rig i also", "rig i also known", "i also known as", "also known as dead box", "known as dead box protein", "as dead box protein 58", "box protein 58 ddx58", "58 ddx58 and", "ddx58 and interferon induced", "and interferon induced helicase c", "interferon induced helicase c domain", "induced helicase c domain containing", "helicase c domain containing protein", "c domain containing protein 1", "containing protein 1 ifih1", "1 ifih1 also", "ifih1 also known as", "as mda5 salvi", "mda5 salvi v", "salvi v et al. 2021", "et al. 2021 campbell", "al. 2021 campbell gr", "2021 campbell gr et", "campbell gr et al. 2021", "et al. 2021 rebendenne", "al. 2021 rebendenne a", "2021 rebendenne a et", "rebendenne a et al. 2021", "a et al. 2021 .", "al. 2021 . the activated", "2021 . the activated prrs", ". the activated prrs trigger", "the activated prrs trigger signaling", "activated prrs trigger signaling pathways", "prrs trigger signaling pathways to", "trigger signaling pathways to produce", "signaling pathways to produce type", "pathways to produce type i", "to produce type i and", "produce type i and type", "type i and type iii", "i and type iii interferons", "and type iii interferons ifns", "type iii interferons ifns and", "iii interferons ifns and proinflammatory", "interferons ifns and proinflammatory mediators", "ifns and proinflammatory mediators that", "and proinflammatory mediators that perform", "proinflammatory mediators that perform antiviral", "mediators that perform antiviral functions.", "that perform antiviral functions. this", "perform antiviral functions. this reactome", "antiviral functions. this reactome module", "functions. this reactome module describes", "this reactome module describes the", "reactome module describes the mechanisms", "module describes the mechanisms underlying", "describes the mechanisms underlying prr", "the mechanisms underlying prr mediated", "mechanisms underlying prr mediated sensing", "underlying prr mediated sensing of", "prr mediated sensing of the", "mediated sensing of the severe", "sensing of the severe acute", "of the severe acute respiratory", "the severe acute respiratory syndrome", "severe acute respiratory syndrome coronavirus", "acute respiratory syndrome coronavirus type", "respiratory syndrome coronavirus type 2", "coronavirus type 2 sars", "type 2 sars cov", "2 sars cov 2", "sars cov 2 infection.", "cov 2 infection. first", "infection. first endosomal recognition", "first endosomal recognition of", "endosomal recognition of viral ssrna", "recognition of viral ssrna occurs", "of viral ssrna occurs by", "viral ssrna occurs by means", "ssrna occurs by means of", "occurs by means of tlr7", "by means of tlr7 and", "means of tlr7 and tlr8", "tlr7 and tlr8 which", "and tlr8 which detect", "tlr8 which detect gu", "which detect gu rich ssrna", "detect gu rich ssrna sequences", "rich ssrna sequences salvi", "ssrna sequences salvi v", "sequences salvi v et", "gr et al. 2021 .", "et al. 2021 . second", "2021 . second sars", ". second sars cov", "second sars cov 2", "sars cov 2 dsrna replication", "cov 2 dsrna replication intermediates", "2 dsrna replication intermediates can", "dsrna replication intermediates can be", "replication intermediates can be recognized", "intermediates can be recognized by", "can be recognized by cytoplasmic", "be recognized by cytoplasmic receptors", "recognized by cytoplasmic receptors ddx58", "by cytoplasmic receptors ddx58 and", "cytoplasmic receptors ddx58 and ifih1", "receptors ddx58 and ifih1 which", "ddx58 and ifih1 which bind", "and ifih1 which bind to", "ifih1 which bind to mitochondrial", "which bind to mitochondrial antiviral", "bind to mitochondrial antiviral signaling", "to mitochondrial antiviral signaling protein", "antiviral signaling protein mavs", "protein mavs ips", "ips 1 to induce", "1 to induce the", "to induce the ifn mediated", "induce the ifn mediated antiviral", "the ifn mediated antiviral response", "mediated antiviral response rebendenne", "antiviral response rebendenne a", "response rebendenne a et", "et al. 2021 yin", "al. 2021 yin x", "2021 yin x et", "yin x et al. 2021", "x et al. 2021 .", "et al. 2021 . in", "al. 2021 . in addition", ". in addition sars", "in addition sars cov", "addition sars cov 2", "sars cov 2 e can", "cov 2 e can be", "2 e can be sensed", "e can be sensed by", "can be sensed by tlr2", "sensed by tlr2 zheng", "by tlr2 zheng m", "tlr2 zheng m et", "zheng m et al. 2021", "m et al. 2021 .", "et al. 2021 . further", "2021 . further cellular", ". further cellular nucleic", "further cellular nucleic acid", "cellular nucleic acid binding protein", "acid binding protein cnbp", "protein cnbp and", "cnbp and la related", "and la related protein 1", "related protein 1 larp1", "1 larp1 can", "larp1 can directly bind", "can directly bind sars cov", "directly bind sars cov 2", "bind sars cov 2 grna", "sars cov 2 grna to", "cov 2 grna to repress", "2 grna to repress sars", "grna to repress sars cov", "to repress sars cov 2", "repress sars cov 2 replication", "cov 2 replication schmidt", "2 replication schmidt n", "replication schmidt n et", "schmidt n et al. 2021", "n et al. 2021 .", "et al. 2021 . this", "al. 2021 . this module", "2021 . this module also", ". this module also describes", "this module also describes several", "module also describes several strategies", "also describes several strategies developed", "describes several strategies developed by", "several strategies developed by sars", "strategies developed by sars cov", "developed by sars cov 2", "by sars cov 2 to", "sars cov 2 to evade", "cov 2 to evade or", "2 to evade or alter", "to evade or alter host", "evade or alter host immunity", "alter host immunity including", "host immunity including escaping", "immunity including escaping innate", "including escaping innate immune sensors", "innate immune sensors inhibiting", "immune sensors inhibiting ifn", "sensors inhibiting ifn production", "inhibiting ifn production and signaling", "production and signaling and", "and signaling and evading", "signaling and evading antiviral", "and evading antiviral function of", "evading antiviral function of ifn", "antiviral function of ifn stimulated", "function of ifn stimulated gene", "ifn stimulated gene isg", "gene isg products.", "isg products. for example", "products. for example sars", "for example sars cov", "example sars cov 2", "sars cov 2 encodes nsp14", "cov 2 encodes nsp14 and", "2 encodes nsp14 and nsp16", "encodes nsp14 and nsp16 which", "nsp14 and nsp16 which possess", "and nsp16 which possess guanine", "nsp16 which possess guanine n7", "which possess guanine n7 methyltransferase", "possess guanine n7 methyltransferase activity", "guanine n7 methyltransferase activity and", "n7 methyltransferase activity and 2\u2019", "methyltransferase activity and 2\u2019 o", "activity and 2\u2019 o methyl", "and 2\u2019 o methyl transferase", "2\u2019 o methyl transferase activity", "o methyl transferase activity respectively", "transferase activity respectively ogando", "activity respectively ogando ns", "respectively ogando ns et", "ogando ns et al. 2020", "et al. 2020 krafcikova", "al. 2020 krafcikova p", "2020 krafcikova p et", "krafcikova p et al. 2020", "et al. 2020 viswanatha", "al. 2020 viswanatha t", "2020 viswanatha t et", "viswanatha t et al. 2020", "et al. 2020 lin", "al. 2020 lin s", "2020 lin s et", "lin s et al. 2021", "et al. 2021 yan", "al. 2021 yan l", "2021 yan l et", "yan l et al. 2021", "l et al. 2021 .", "al. 2021 . in human", "2021 . in human coronaviruses", ". in human coronaviruses nsp14", "in human coronaviruses nsp14 generates", "human coronaviruses nsp14 generates 5'", "coronaviruses nsp14 generates 5' cap", "nsp14 generates 5' cap 0", "generates 5' cap 0 viral", "5' cap 0 viral rna", "0 viral rna m7gpppn", "rna m7gpppn guanine", "m7gpppn guanine n7 methylated", "guanine n7 methylated and", "n7 methylated and nsp16", "methylated and nsp16 further", "and nsp16 further methylates cap", "nsp16 further methylates cap 0", "further methylates cap 0 viral", "methylates cap 0 viral rna.", "cap 0 viral rna. these", "0 viral rna. these viral", "viral rna. these viral rna", "rna. these viral rna modifications", "these viral rna modifications mimic", "viral rna modifications mimic the", "rna modifications mimic the 5'", "modifications mimic the 5' cap", "mimic the 5' cap structure", "the 5' cap structure of", "5' cap structure of host", "cap structure of host mrnas", "structure of host mrnas allowing", "of host mrnas allowing the", "host mrnas allowing the virus", "mrnas allowing the virus to", "allowing the virus to efficiently", "the virus to efficiently evade", "virus to efficiently evade recognition", "to efficiently evade recognition by", "efficiently evade recognition by cytosolic", "evade recognition by cytosolic ddx58", "recognition by cytosolic ddx58 and", "by cytosolic ddx58 and ifih1", "ddx58 and ifih1 chen", "and ifih1 chen y", "ifih1 chen y et", "chen y et al. 2009", "et al. 2009 2011", "2009 2011 daffis", "2011 daffis s et", "daffis s et al. 2010", "et al. 2010 shown", "al. 2010 shown for", "2010 shown for covs", "shown for covs such as", "for covs such as sars", "covs such as sars cov", "such as sars cov 1", "as sars cov 1 and", "sars cov 1 and mers", "cov 1 and mers cov", "1 and mers cov .", "and mers cov . structural", "mers cov . structural studies", "cov . structural studies and", ". structural studies and computational", "structural studies and computational analysis", "studies and computational analysis suggest", "and computational analysis suggest that", "computational analysis suggest that properties", "analysis suggest that properties and", "suggest that properties and biological", "that properties and biological functions", "properties and biological functions of", "and biological functions of sars", "biological functions of sars cov", "functions of sars cov 2", "of sars cov 2 nsp14", "sars cov 2 nsp14 and", "cov 2 nsp14 and nsp16", "2 nsp14 and nsp16 could", "nsp14 and nsp16 could be", "and nsp16 could be very", "nsp16 could be very similar", "could be very similar to", "be very similar to these", "very similar to these of", "similar to these of sars", "to these of sars cov", "these of sars cov 1", "sars cov 1 rosas", "cov 1 rosas lemus", "1 rosas lemus m", "rosas lemus m et al.", "lemus m et al. 2020", "lin s et al. 2020", "et al. 2020 viswanathan", "al. 2020 viswanathan t", "2020 viswanathan t et", "viswanathan t et al. 2020", "et al. 2020 jiang", "al. 2020 jiang y", "2020 jiang y et", "jiang y et al. 2020", "et al. 2020 wilamowski", "al. 2020 wilamowski m", "2020 wilamowski m et", "wilamowski m et al. 2021", "2021 . further the", ". further the uridylate\u2010specific", "further the uridylate\u2010specific endoribonuclease", "the uridylate\u2010specific endoribonuclease endou", "endoribonuclease endou activity", "endou activity of sars", "activity of sars cov 2", "of sars cov 2 nsp15", "sars cov 2 nsp15 degrades", "cov 2 nsp15 degrades viral", "2 nsp15 degrades viral rna", "nsp15 degrades viral rna to", "degrades viral rna to hide", "viral rna to hide it", "rna to hide it from", "to hide it from innate", "hide it from innate immune", "it from innate immune sensors", "innate immune sensors frazier", "immune sensors frazier mn", "sensors frazier mn et", "frazier mn et al. 2021", "mn et al. 2021 .", "et al. 2021 . moreover", "2021 . moreover sars", ". moreover sars cov", "moreover sars cov 2", "sars cov 2 encodes several", "cov 2 encodes several proteins", "2 encodes several proteins that", "encodes several proteins that directly", "several proteins that directly bind", "proteins that directly bind to", "that directly bind to host", "directly bind to host targets", "bind to host targets associated", "to host targets associated with", "host targets associated with sars\u2011cov\u20112", "targets associated with sars\u2011cov\u20112 infection", "associated with sars\u2011cov\u20112 infection and", "with sars\u2011cov\u20112 infection and cytokine", "sars\u2011cov\u20112 infection and cytokine production", "and cytokine production shin", "cytokine production shin d", "production shin d et", "shin d et al. 2020", "et al. 2020 xia", "al. 2020 xia h", "2020 xia h et", "xia h et al. 2020", "et al. 2020 matsuyama", "al. 2020 matsuyama t", "2020 matsuyama t et", "matsuyama t et al. 2020", "et al. 2020 yuen", "al. 2020 yuen ck", "2020 yuen ck et", "yuen ck et al. 2020", "et al. 2020 reviewed", "al. 2020 reviewed by", "2020 reviewed by park", "reviewed by park a &", "by park a & iwasaki", "park a & iwasaki a", "a & iwasaki a 2020", "& iwasaki a 2020 .", "iwasaki a 2020 . this", "a 2020 . this reactome", "2020 . this reactome module", ". this reactome module describes", "this reactome module describes several", "reactome module describes several such", "module describes several such binding", "describes several such binding events", "several such binding events and", "such binding events and their", "binding events and their consequences.", "events and their consequences. for", "and their consequences. for example", "consequences. for example as", "for example as a", "example as a deubiquitinating", "as a deubiquitinating and deisgylating", "a deubiquitinating and deisgylating enzyme", "and deisgylating enzyme viral", "deisgylating enzyme viral nsp3", "enzyme viral nsp3 binds", "viral nsp3 binds to and", "nsp3 binds to and removes", "binds to and removes isg15", "to and removes isg15 from", "and removes isg15 from signaling", "removes isg15 from signaling proteins", "isg15 from signaling proteins such", "from signaling proteins such as", "signaling proteins such as irf3", "proteins such as irf3 and", "such as irf3 and ifih1", "as irf3 and ifih1 thereby", "irf3 and ifih1 thereby modulating", "and ifih1 thereby modulating the", "ifih1 thereby modulating the formation", "thereby modulating the formation of", "modulating the formation of signaling", "the formation of signaling complexes", "formation of signaling complexes and", "of signaling complexes and the", "signaling complexes and the activation", "complexes and the activation of", "and the activation of irf3/7", "the activation of irf3/7 and", "activation of irf3/7 and nf", "of irf3/7 and nf kappab", "and nf kappab liu", "nf kappab liu cq", "kappab liu cq et", "liu cq et al. 2021", "cq et al. 2021 .", "et al. 2021 . binding", "al. 2021 . binding of", "2021 . binding of sars", ". binding of sars cov", "binding of sars cov 2", "of sars cov 2 nsp6", "cov 2 nsp6 nsp13", "2 nsp6 nsp13 or", "nsp6 nsp13 or membrane", "nsp13 or membrane m", "membrane m protein", "m protein to cytosolic", "protein to cytosolic tbk1 prevents", "to cytosolic tbk1 prevents irf3/7", "cytosolic tbk1 prevents irf3/7 activation", "tbk1 prevents irf3/7 activation and", "prevents irf3/7 activation and inhibits", "irf3/7 activation and inhibits ifn", "activation and inhibits ifn production", "and inhibits ifn production downstream", "inhibits ifn production downstream of", "ifn production downstream of ddx58", "downstream of ddx58 ifih1", "ddx58 ifih1 mavs", "ifih1 mavs and sting", "mavs and sting signaling pathways", "sting signaling pathways xia", "signaling pathways xia h", "pathways xia h et", "et al. 2020 sui", "al. 2020 sui l", "2020 sui l et", "sui l et al. 2021", "et al. 2021 . next", "2021 . next m", ". next m protein", "next m protein targets", "m protein targets mavs to", "protein targets mavs to prevent", "targets mavs to prevent the", "mavs to prevent the formation", "to prevent the formation of", "prevent the formation of the", "the formation of the mavs", "formation of the mavs signalosome", "of the mavs signalosome complex", "the mavs signalosome complex and", "mavs signalosome complex and thereby", "signalosome complex and thereby inhibits", "complex and thereby inhibits downstream", "and thereby inhibits downstream signaling", "thereby inhibits downstream signaling pathways", "inhibits downstream signaling pathways of", "downstream signaling pathways of ddx58", "signaling pathways of ddx58 and", "pathways of ddx58 and ifih1", "ddx58 and ifih1 fu", "and ifih1 fu yz", "ifih1 fu yz et", "fu yz et al. 2021", "yz et al. 2021 .", "of sars cov 2 nucleocapsid", "cov 2 nucleocapsid n", "nucleocapsid n protein", "n protein to e3", "protein to e3 ubiquitin ligase", "to e3 ubiquitin ligase trim25", "e3 ubiquitin ligase trim25 inhibits", "ubiquitin ligase trim25 inhibits trim25", "ligase trim25 inhibits trim25 mediated", "trim25 inhibits trim25 mediated ddx58", "inhibits trim25 mediated ddx58 ubiquitination", "trim25 mediated ddx58 ubiquitination and", "mediated ddx58 ubiquitination and the", "ddx58 ubiquitination and the ddx58", "ubiquitination and the ddx58 signaling", "and the ddx58 signaling pathway", "ddx58 signaling pathway gori", "signaling pathway gori sg", "pathway gori sg et", "gori sg et al. 2021", "sg et al. 2021 .", "et al. 2021 . n", "al. 2021 . n interacts", "2021 . n interacts with", ". n interacts with nlrp3", "n interacts with nlrp3 to", "interacts with nlrp3 to promote", "with nlrp3 to promote the", "nlrp3 to promote the assembly", "to promote the assembly and", "promote the assembly and activation", "the assembly and activation of", "assembly and activation of the", "and activation of the nlrp3", "activation of the nlrp3 inflammasome", "the nlrp3 inflammasome pan", "nlrp3 inflammasome pan p", "inflammasome pan p et", "pan p et al. 2021", "al. 2021 . the interaction", "2021 . the interaction between", ". the interaction between viral", "the interaction between viral n", "interaction between viral n and", "between viral n and masp2", "viral n and masp2 promotes", "n and masp2 promotes masp2", "and masp2 promotes masp2 mediated", "masp2 promotes masp2 mediated cleavage", "promotes masp2 mediated cleavage of", "masp2 mediated cleavage of c4", "cleavage of c4 ali", "of c4 ali ym", "c4 ali ym et", "ali ym et al. 2021", "et al. 2021 and", "al. 2021 and c2", "and c2 kang s", "c2 kang s et", "kang s et al. 2021", "et al. 2021 leading", "al. 2021 leading to", "2021 leading to the", "leading to the hyperactivation of", "to the hyperactivation of the", "the hyperactivation of the complement", "hyperactivation of the complement system.", "of the complement system. besides", "complement system. besides viral", "system. besides viral n", "besides viral n promotes", "viral n promotes nf kappab", "n promotes nf kappab activation", "promotes nf kappab activation by", "nf kappab activation by targeting", "kappab activation by targeting signaling", "activation by targeting signaling complexes", "by targeting signaling complexes of", "targeting signaling complexes of tak1", "signaling complexes of tak1 and", "complexes of tak1 and ikk", "tak1 and ikk wu", "and ikk wu y", "ikk wu y et", "wu y et al. 2021", "y et al. 2021 .", "al. 2021 . the ion", "2021 . the ion channel", ". the ion channel activities", "the ion channel activities of", "ion channel activities of accessory", "channel activities of accessory protein", "activities of accessory protein orf3a", "of accessory protein orf3a or", "accessory protein orf3a or 3a", "orf3a or 3a open", "or 3a open reading", "3a open reading frame", "reading frame 3a and", "frame 3a and sars\u2011cov\u20112", "3a and sars\u2011cov\u20112 envelope", "and sars\u2011cov\u20112 envelope e", "envelope e protein", "e protein contribute to", "protein contribute to activation of", "contribute to activation of the", "to activation of the nlrp3", "of the nlrp3 inflammasome leading", "the nlrp3 inflammasome leading to", "nlrp3 inflammasome leading to highly", "inflammasome leading to highly inflammatory", "leading to highly inflammatory pyroptotic", "to highly inflammatory pyroptotic cell", "highly inflammatory pyroptotic cell death", "pyroptotic cell death based", "cell death based on", "death based on findings", "based on findings for sars", "on findings for sars cov", "findings for sars cov 1", "sars cov 1 siu", "cov 1 siu kl", "1 siu kl et", "siu kl et al. 2019", "kl et al. 2019 .", "et al. 2019 . sars", "al. 2019 . sars cov", "2019 . sars cov 2", ". sars cov 2 nsp5", "sars cov 2 nsp5 protease", "2 nsp5 protease 3clpro", "protease 3clpro cleaves", "cleaves tab1 a component", "tab1 a component of", "a component of the tak1", "component of the tak1 complex", "the tak1 complex thus", "tak1 complex thus inhibiting", "complex thus inhibiting nf", "thus inhibiting nf kappab activation", "nf kappab activation moustaqil", "kappab activation moustaqil m", "activation moustaqil m et", "moustaqil m et al .2021", "m et al .2021 .", "et al .2021 . 3clpro", "al .2021 . 3clpro targets", ".2021 . 3clpro targets nlrp12", ". 3clpro targets nlrp12 which", "3clpro targets nlrp12 which modulates", "targets nlrp12 which modulates the", "nlrp12 which modulates the expression", "which modulates the expression of", "modulates the expression of inflammatory", "the expression of inflammatory cytokines", "expression of inflammatory cytokines through", "of inflammatory cytokines through the", "inflammatory cytokines through the regulation", "cytokines through the regulation of", "through the regulation of the", "the regulation of the nfkappab", "regulation of the nfkappab and", "of the nfkappab and mapk", "the nfkappab and mapk pathways", "and mapk pathways moustaqil", "mapk pathways moustaqil m", "pathways moustaqil m et", "moustaqil m et al. 2021", "et al. 2021 . sars", "al. 2021 . sars cov", "2021 . sars cov 2", ". sars cov 2 6", "cov 2 6 orf6", "6 orf6 interacts", "orf6 interacts with importin", "interacts with importin kpna2 and", "with importin kpna2 and components", "importin kpna2 and components of", "kpna2 and components of the", "and components of the nuclear", "components of the nuclear pore", "of the nuclear pore complex", "nuclear pore complex nup98", "pore complex nup98 and", "complex nup98 and rae1", "nup98 and rae1 to", "and rae1 to block", "rae1 to block nuclear", "to block nuclear translocation of", "block nuclear translocation of irf3", "translocation of irf3 stat1", "of irf3 stat1 and", "irf3 stat1 and stat2", "stat1 and stat2 xia", "and stat2 xia h", "stat2 xia h et", "et al. 2020 miorin", "al. 2020 miorin l", "2020 miorin l et", "miorin l et al. 2020", "l et al. 2020 .", "et al. 2020 . sars", "al. 2020 . sars cov", "2020 . sars cov 2", ". sars cov 2 9b", "cov 2 9b orf9b", "9b orf9b inhibits", "orf9b inhibits the mavs", "inhibits the mavs mediated production", "the mavs mediated production of", "mavs mediated production of type", "mediated production of type i", "production of type i ifns", "of type i ifns by", "type i ifns by targeting", "i ifns by targeting tomm70", "ifns by targeting tomm70 on", "by targeting tomm70 on the", "targeting tomm70 on the mitochondria", "on the mitochondria jiang", "the mitochondria jiang hw", "mitochondria jiang hw et", "jiang hw et al. 2020", "hw et al. 2020 .", "et al. 2020 . binding", "al. 2020 . binding of", "2020 . binding of mitochondrial", ". binding of mitochondrial viral", "binding of mitochondrial viral 9", "of mitochondrial viral 9 to", "mitochondrial viral 9 to ikbkg", "viral 9 to ikbkg prevents", "9 to ikbkg prevents mavs", "to ikbkg prevents mavs dependent", "ikbkg prevents mavs dependent nf", "prevents mavs dependent nf kappab", "mavs dependent nf kappab activation", "nf kappab activation wu", "kappab activation wu j", "activation wu j et", "wu j et al. 2021", "j et al. 2021 .", "et al. 2021 . although", "al. 2021 . although the", "2021 . although the evasion", ". although the evasion mechanisms", "although the evasion mechanisms are", "the evasion mechanisms are mainly", "evasion mechanisms are mainly conserved", "mechanisms are mainly conserved between", "are mainly conserved between sars", "mainly conserved between sars cov", "conserved between sars cov 1", "between sars cov 1 and", "sars cov 1 and sars", "cov 1 and sars cov", "1 and sars cov 2", "sars cov 2 gordon", "cov 2 gordon de", "2 gordon de et", "gordon de et al. 2020", "al. 2020 studies", "2020 studies identified", "studies identified sars cov 2", "identified sars cov 2 specific", "sars cov 2 specific modulations", "cov 2 specific modulations of", "2 specific modulations of host", "specific modulations of host immune", "modulations of host immune response", "of host immune response that", "host immune response that may", "immune response that may contribute", "response that may contribute to", "that may contribute to pathophysiological", "may contribute to pathophysiological determinants", "contribute to pathophysiological determinants of", "to pathophysiological determinants of covid", "pathophysiological determinants of covid 19", "of covid 19 gordon", "covid 19 gordon de", "19 gordon de et", "et al. 2020 schiller", "al. 2020 schiller hb", "2020 schiller hb et", "schiller hb et al. 2021", "hb et al. 2021 .", "al. 2021 . this reactome", "2021 . this reactome module", "reactome module describes several virus", "module describes several virus host", "describes several virus host interactions", "several virus host interactions identified", "virus host interactions identified in", "host interactions identified in cells", "interactions identified in cells during", "identified in cells during sars", "in cells during sars cov", "cells during sars cov 2", "sars cov 2 but", "cov 2 but not", "2 but not sars", "but not sars cov 1", "sars cov 1 infection.", "cov 1 infection. for", "1 infection. for example", "infection. for example sars", "cov 2 8 orf8", "8 orf8 regulates", "orf8 regulates the expression", "regulates the expression of class", "the expression of class i", "expression of class i mhc", "of class i mhc on", "class i mhc on the", "i mhc on the surface", "mhc on the surface of", "on the surface of the", "the surface of the infected", "surface of the infected cells", "of the infected cells through", "the infected cells through an", "infected cells through an autophagy", "cells through an autophagy dependent", "through an autophagy dependent lysosomal", "an autophagy dependent lysosomal degradation", "autophagy dependent lysosomal degradation of", "dependent lysosomal degradation of class", "lysosomal degradation of class i", "degradation of class i mhc", "class i mhc zhang", "i mhc zhang y", "mhc zhang y et", "zhang y et al. 2021", "et al. 2021 . at", "al. 2021 . at the", "2021 . at the plasma", ". at the plasma membrane", "the plasma membrane binding", "plasma membrane binding of", "membrane binding of secreted", "binding of secreted viral 8", "of secreted viral 8 to", "secreted viral 8 to il17ra", "viral 8 to il17ra activates", "8 to il17ra activates il17", "to il17ra activates il17 signaling", "il17ra activates il17 signaling pathway", "activates il17 signaling pathway leading", "il17 signaling pathway leading to", "signaling pathway leading to an", "pathway leading to an increased", "leading to an increased secretion", "to an increased secretion of", "an increased secretion of cytokines/chemokines", "increased secretion of cytokines/chemokines thus", "secretion of cytokines/chemokines thus contributing", "of cytokines/chemokines thus contributing to", "cytokines/chemokines thus contributing to cytokine", "thus contributing to cytokine storm", "contributing to cytokine storm during", "to cytokine storm during sars", "cytokine storm during sars cov", "storm during sars cov 2", "during sars cov 2 infection", "cov 2 infection lin", "2 infection lin x", "infection lin x et", "lin x et al. 2021", "et al. 2021 . furthermore", "2021 . furthermore sars", ". furthermore sars cov", "furthermore sars cov 2", "sars cov 2 host interactome", "cov 2 host interactome and", "2 host interactome and proteomics", "host interactome and proteomics studies", "interactome and proteomics studies identified", "and proteomics studies identified various", "proteomics studies identified various human", "studies identified various human proteins", "identified various human proteins that", "various human proteins that are", "human proteins that are targeted", "proteins that are targeted by", "that are targeted by sars", "are targeted by sars cov", "targeted by sars cov 2", "by sars cov 2 proteins", "cov 2 proteins gordon", "2 proteins gordon de", "proteins gordon de et", "gordon de et al. 2020a", "et al. 2020a b", "2020a b bojkova", "b bojkova d et", "bojkova d et al. 2020", "et al. 2020 stukalov", "al. 2020 stukalov a", "2020 stukalov a et", "stukalov a et al. 2021", "et al. 2021 li", "al. 2021 li j", "2021 li j et", "li j et al. 2021", "et al. 2021 messina", "al. 2021 messina f", "2021 messina f et", "messina f et al. 2021", "f et al. 2021 .", ". this reactome module does", "this reactome module does not", "reactome module does not cover", "module does not cover all", "does not cover all identified", "not cover all identified sars", "cover all identified sars cov", "all identified sars cov 2\u2013human", "identified sars cov 2\u2013human interactions", "cov 2\u2013human interactions the", "2\u2013human interactions the module", "interactions the module describes", "the module describes those associations", "module describes those associations that", "describes those associations that were", "those associations that were functionally", "associations that were functionally validated." ] }, { "record_id": "GLY_000594_1_1874", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9709570", "r hsa", "hsa 9709570", "r hsa 9709570" ] }, { "record_id": "GLY_000594_1_1874", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "impaired brca2", "brca2 binding", "binding to", "to rad51", "impaired brca2 binding", "brca2 binding to", "binding to rad51", "impaired brca2 binding to", "brca2 binding to rad51", "impaired brca2 binding to rad51", "a critical", "critical function", "function of", "of brca2", "brca2 is", "is to", "to bind", "bind rad51", "rad51 and", "and nucleate", "nucleate rad51", "rad51 filament", "filament formation", "formation on", "on single", "single stranded", "stranded dna.", "dna. brca2", "brca2 has", "has two", "two regions", "regions that", "that interact", "interact with", "with rad51:", "rad51: 8", "8 brc", "brc repeats", "repeats encoded", "encoded by", "by exon11", "bork et", "et al.", "al. 1996", "wong et", "al. 1997", "and a", "a c", "c terminal", "terminal rad51", "rad51 binding", "binding domain", "domain called", "called tr2", "sharan et", "1997 .", "a critical function", "critical function of", "function of brca2", "of brca2 is", "brca2 is to", "is to bind", "to bind rad51", "bind rad51 and", "rad51 and nucleate", "and nucleate rad51", "nucleate rad51 filament", "rad51 filament formation", "filament formation on", "formation on single", "on single stranded", "single stranded dna.", "stranded dna. brca2", "dna. brca2 has", "brca2 has two", "has two regions", "two regions that", "regions that interact", "that interact with", "interact with rad51:", "with rad51: 8", "rad51: 8 brc", "8 brc repeats", "brc repeats encoded", "repeats encoded by", "encoded by exon11", "exon11 bork", "bork et al.", "et al. 1996", "1996 wong", "wong et al.", "et al. 1997", "1997 and", "and a c", "a c terminal", "c terminal rad51", "terminal rad51 binding", "rad51 binding domain", "binding domain called", "domain called tr2", "tr2 sharan", "sharan et al.", "al. 1997 .", "a critical function of", "critical function of brca2", "function of brca2 is", "of brca2 is to", "brca2 is to bind", "is to bind rad51", "to bind rad51 and", "bind rad51 and nucleate", "rad51 and nucleate rad51", "and nucleate rad51 filament", "nucleate rad51 filament formation", "rad51 filament formation on", "filament formation on single", "formation on single stranded", "on single stranded dna.", "single stranded dna. brca2", "stranded dna. brca2 has", "dna. brca2 has two", "brca2 has two regions", "has two regions that", "two regions that interact", "regions that interact with", "that interact with rad51:", "interact with rad51: 8", "with rad51: 8 brc", "rad51: 8 brc repeats", "8 brc repeats encoded", "brc repeats encoded by", "repeats encoded by exon11", "by exon11 bork", "exon11 bork et", "bork et al. 1996", "al. 1996 wong", "1996 wong et", "wong et al. 1997", "al. 1997 and", "1997 and a", "and a c terminal", "a c terminal rad51", "c terminal rad51 binding", "terminal rad51 binding domain", "rad51 binding domain called", "binding domain called tr2", "called tr2 sharan", "tr2 sharan et", "sharan et al. 1997", "et al. 1997 .", "a critical function of brca2", "critical function of brca2 is", "function of brca2 is to", "of brca2 is to bind", "brca2 is to bind rad51", "is to bind rad51 and", "to bind rad51 and nucleate", "bind rad51 and nucleate rad51", "rad51 and nucleate rad51 filament", "and nucleate rad51 filament formation", "nucleate rad51 filament formation on", "rad51 filament formation on single", "filament formation on single stranded", "formation on single stranded dna.", "on single stranded dna. brca2", "single stranded dna. brca2 has", "stranded dna. brca2 has two", "dna. brca2 has two regions", "brca2 has two regions that", "has two regions that interact", "two regions that interact with", "regions that interact with rad51:", "that interact with rad51: 8", "interact with rad51: 8 brc", "with rad51: 8 brc repeats", "rad51: 8 brc repeats encoded", "8 brc repeats encoded by", "brc repeats encoded by exon11", "encoded by exon11 bork", "by exon11 bork et", "exon11 bork et al.", "et al. 1996 wong", "al. 1996 wong et", "1996 wong et al.", "et al. 1997 and", "al. 1997 and a", "1997 and a c", "and a c terminal rad51", "a c terminal rad51 binding", "c terminal rad51 binding domain", "terminal rad51 binding domain called", "rad51 binding domain called tr2", "domain called tr2 sharan", "called tr2 sharan et", "tr2 sharan et al.", "sharan et al. 1997 ." ] }, { "record_id": "GLY_000594_1_1875", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9709603", "r hsa", "hsa 9709603", "r hsa 9709603" ] }, { "record_id": "GLY_000594_1_1875", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "impaired brca2", "brca2 binding", "binding to", "to palb2", "impaired brca2 binding", "brca2 binding to", "binding to palb2", "impaired brca2 binding to", "brca2 binding to palb2", "impaired brca2 binding to palb2", "this pathway", "pathway describes", "describes brca2", "brca2 missense", "missense mutations", "mutations that", "that affect", "affect the", "the n", "n terminus", "terminus of", "of brca2", "brca2 and", "and impair", "impair the", "the ability", "ability of", "brca2 to", "to bind", "bind palb2", "which is", "is a", "a crucial", "crucial step", "step in", "in homologous", "homologous recombination", "recombination repair", "of dna", "dna double", "double strand", "strand breaks", "xia et", "et al.", "al. 2006", "2006 .", "this pathway describes", "pathway describes brca2", "describes brca2 missense", "brca2 missense mutations", "missense mutations that", "mutations that affect", "that affect the", "affect the n", "the n terminus", "n terminus of", "terminus of brca2", "of brca2 and", "brca2 and impair", "and impair the", "impair the ability", "the ability of", "ability of brca2", "of brca2 to", "brca2 to bind", "to bind palb2", "palb2 which", "which is a", "is a crucial", "a crucial step", "crucial step in", "step in homologous", "in homologous recombination", "homologous recombination repair", "repair hrr", "hrr of", "of dna double", "dna double strand", "double strand breaks", "breaks dsbs", "xia et al.", "et al. 2006", "al. 2006 .", "this pathway describes brca2", "pathway describes brca2 missense", "describes brca2 missense mutations", "brca2 missense mutations that", "missense mutations that affect", "mutations that affect the", "that affect the n", "affect the n terminus", "the n terminus of", "n terminus of brca2", "terminus of brca2 and", "of brca2 and impair", "brca2 and impair the", "and impair the ability", "impair the ability of", "the ability of brca2", "ability of brca2 to", "of brca2 to bind", "brca2 to bind palb2", "bind palb2 which", "palb2 which is", "which is a crucial", "is a crucial step", "a crucial step in", "crucial step in homologous", "step in homologous recombination", "in homologous recombination repair", "recombination repair hrr", "hrr of dna", "of dna double strand", "dna double strand breaks", "strand breaks dsbs", "dsbs xia", "xia et al. 2006", "et al. 2006 .", "this pathway describes brca2 missense", "pathway describes brca2 missense mutations", "describes brca2 missense mutations that", "brca2 missense mutations that affect", "missense mutations that affect the", "mutations that affect the n", "that affect the n terminus", "affect the n terminus of", "the n terminus of brca2", "n terminus of brca2 and", "terminus of brca2 and impair", "of brca2 and impair the", "brca2 and impair the ability", "and impair the ability of", "impair the ability of brca2", "the ability of brca2 to", "ability of brca2 to bind", "of brca2 to bind palb2", "to bind palb2 which", "bind palb2 which is", "palb2 which is a", "which is a crucial step", "is a crucial step in", "a crucial step in homologous", "crucial step in homologous recombination", "step in homologous recombination repair", "homologous recombination repair hrr", "repair hrr of", "hrr of dna double", "of dna double strand breaks", "double strand breaks dsbs", "dsbs xia et", "xia et al. 2006 ." ] }, { "record_id": "GLY_000594_1_1876", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9748787", "r hsa", "hsa 9748787", "r hsa 9748787" ] }, { "record_id": "GLY_000594_1_1876", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "azathioprine adme", "thiopurines were", "were originally", "originally developed", "developed for", "for cancer", "cancer treatment", "treatment in", "in the", "the early", "early 1950s", "with 6", "6 mercaptopurine", "being the", "the first", "first thiopurine", "thiopurine approved", "approved by", "by the", "the fda", "fda for", "for the", "the treatment", "treatment of", "of leukaemia", "just two", "two years", "years after", "after its", "its discovery.", "discovery. azathioprine", "a prodrug", "prodrug of", "of 6mp", "was developed", "developed by", "the addition", "addition of", "of a", "a nitroimidazol", "nitroimidazol group", "group a", "a few", "few years", "years later", "later to", "to bypass", "bypass the", "the high", "high first", "first pass", "pass metabolism", "metabolism of", "6mp due", "due to", "to oxidation", "oxidation in", "in intestinal", "intestinal cells", "cells by", "by xanthine", "xanthine oxidase", "xdh .", ". aza", "aza is", "is a", "a thiopurine", "thiopurine prodrug", "and its", "its pharmacological", "pharmacological action", "action is", "is based", "based on", "on the", "the release", "release of", "of the", "the active", "active metabolite", "metabolite 6", "which is", "is further", "further metabolised", "metabolised to", "to pharmacoligically", "pharmacoligically active", "active 6", "6 thioguanine", "thioguanine nucleotides", "6 tgns", "tgns .", ". these", "these 6", "tgns achieve", "achieve their", "their cytotoxic", "cytotoxic effects", "effects in", "in one", "one of", "of four", "four ways

              1.", "ways

              1. incorporation", "incorporation of", "of 6", "6 thioguanosine", "thioguanosine triphosphate", "into rna
              2.", "rna
              2. incorporation", "6 thiodeoxyguanosine", "thiodeoxyguanosine triphosphate", "into dna
              3.", "dna
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              acetylsalicylic", "1977 .
              acetylsalicylic acid", ".
              acetylsalicylic acid is", "acid is only", "is only slightly", "only slightly soluble", "slightly soluble in", "soluble in conditions", "in conditions being", "conditions being found", "being found in", "found in the", "in the stomach", "the stomach mucosa", "mucosa mostly", "mostly because of", "because of unavailability", "of unavailability of", "unavailability of sufficient", "of sufficient amount", "sufficient amount of", "amount of solvent.", "of solvent. the", "solvent. the absorption", "absorption as", "as well as", "well as the", "as the absorbing", "the absorbing area", "area increases", "increases in the", "in the small", "the small intestine.", "small intestine. further", "intestine. further increased", "further increased absorption", "increased absorption is", "absorption is achieved", "is achieved by", "achieved by dissolving", "by dissolving tablets", "dissolving tablets before", "tablets before ingestion", "before ingestion or", "ingestion or usage", "or usage of", "usage of asa", "of asa salts", "salts dressman", "dressman et al", "al 2012", "2012 . practically", ". practically 100%", "practically 100% of", "100% of therapeutic", "of therapeutic aspirin", "therapeutic aspirin doses", "aspirin doses are", "doses are taken", "are taken up", "up mostly", "mostly by intestinal", "by intestinal mucosal", "intestinal mucosal cells", "cells artursson", "artursson & karlsson", "karlsson 1991", "1991 yee", "yee 1997 .
              only", "1997 .
              only a", ".
              only a few", "a few percent", "few percent of", "percent of asa", "asa remain", "unchanged the", "the rest is", "rest is hydrolyzed", "is hydrolyzed to", "hydrolyzed to salicylate", "st . the", ". the major", "the major route", "major route of", "route of st", "of st catabolism", "st catabolism is", "catabolism is conjugation", "is conjugation with", "conjugation with glycine", "with glycine to", "glycine to form", "to form salicyluric", "form salicyluric acid.", "salicyluric acid. this", "acid. this accounts", "this accounts for", "accounts for 20\u201365%", "for 20\u201365% of", "20\u201365% of the", "of the products.", "the products. conjugation", "products. conjugation to", "conjugation to glucuronides", "glucuronides ester", "ester and ether", "ether removes", "removes up to", "up to 42%", "to 42% of", "42% of st.", "of st. finally", "finally a", "a minor part", "minor part also", "part also gets", "also gets hydroxylated", "gets hydroxylated by", "hydroxylated by cytochromes", "cytochromes hutt", "hutt et al", "al 1986", "water aspirin acetylsalicylic", "aspirin acetylsalicylic acid", "acetylsalicylic acid asa", "dissolves dissociating into", "dissociating into the acetylsalicylate", "into the acetylsalicylate ion", "acetylsalicylate ion asa", "asa . asa", ". asa is", "asa is an", "is an anti clotting", "an anti clotting agent", "anti clotting agent and", "clotting agent and nonsteroidal", "agent and nonsteroidal anti", "and nonsteroidal anti inflammatory", "nonsteroidal anti inflammatory drug", "inflammatory drug nsaid", "nsaid the", "the therapeutic effects are", "therapeutic effects are mediated", "effects are mediated through", "are mediated through its", "mediated through its interaction", "through its interaction with", "its interaction with ptgs", "interaction with ptgs enzymes.", "with ptgs enzymes. on", "ptgs enzymes. on a", "enzymes. on a molar", "on a molar basis", "a molar basis asa", "asa a", "a is more", "is more potent as", "more potent as an", "potent as an analgesic/anti", "as an analgesic/anti inflammatory", "an analgesic/anti inflammatory agent", "agent b", "b has greater", "has greater gastric ulcerogenic", "greater gastric ulcerogenic activity", "ulcerogenic activity and", "c is much", "is much more effective", "much more effective as", "more effective as an", "effective as an inhibitor", "as an inhibitor of", "an inhibitor of prostaglandin", "inhibitor of prostaglandin biosynthesis", "of prostaglandin biosynthesis and", "prostaglandin biosynthesis and platelet", "biosynthesis and platelet aggregation", "and platelet aggregation than", "platelet aggregation than salicylate", "than salicylate st", "st flower", "flower 1974 mills", "1974 mills et", "et al 1974", "1974 rainsford 1975", "rainsford 1975 rainsford", "1975 rainsford 1977", "rainsford 1977 .
              acetylsalicylic acid", "1977 .
              acetylsalicylic acid is", ".
              acetylsalicylic acid is only", "acid is only slightly", "is only slightly soluble", "only slightly soluble in", "slightly soluble in conditions", "soluble in conditions being", "in conditions being found", "conditions being found in", "being found in the", "found in the stomach", "in the stomach mucosa", "stomach mucosa mostly", "mucosa mostly because", "mostly because of unavailability", "because of unavailability of", "of unavailability of sufficient", "unavailability of sufficient amount", "of sufficient amount of", "sufficient amount of solvent.", "amount of solvent. the", "of solvent. the absorption", "the absorption as", "absorption as well", "as well as the", "well as the absorbing", "as the absorbing area", "absorbing area increases", "area increases in", "increases in the small", "in the small intestine.", "the small intestine. further", "small intestine. further increased", "intestine. further increased absorption", "further increased absorption is", "increased absorption is achieved", "absorption is achieved by", "is achieved by dissolving", "achieved by dissolving tablets", "by dissolving tablets before", "dissolving tablets before ingestion", "tablets before ingestion or", "before ingestion or usage", "ingestion or usage of", "or usage of asa", "usage of asa salts", "asa salts dressman", "salts dressman et", "et al 2012", "al 2012 .", "2012 . practically 100%", ". practically 100% of", "practically 100% of therapeutic", "100% of therapeutic aspirin", "of therapeutic aspirin doses", "therapeutic aspirin doses are", "aspirin doses are taken", "doses are taken up", "taken up mostly", "up mostly by", "mostly by intestinal mucosal", "by intestinal mucosal cells", "mucosal cells artursson", "cells artursson &", "& karlsson 1991", "1991 yee 1997", "yee 1997 .
              only a", "1997 .
              only a few", ".
              only a few percent", "a few percent of", "few percent of asa", "of asa remain", "asa remain unchanged", "remain unchanged the", "unchanged the rest", "the rest is hydrolyzed", "rest is hydrolyzed to", "is hydrolyzed to salicylate", "to salicylate st", "salicylate st .", "st . the major", ". the major route", "the major route of", "major route of st", "route of st catabolism", "of st catabolism is", "st catabolism is conjugation", "catabolism is conjugation with", "is conjugation with glycine", "conjugation with glycine to", "with glycine to form", "glycine to form salicyluric", "to form salicyluric acid.", "form salicyluric acid. this", "salicyluric acid. this accounts", "acid. this accounts for", "this accounts for 20\u201365%", "accounts for 20\u201365% of", "for 20\u201365% of the", "20\u201365% of the products.", "of the products. conjugation", "the products. conjugation to", "products. conjugation to glucuronides", "to glucuronides ester", "glucuronides ester and", "and ether removes", "ether removes up", "removes up to 42%", "up to 42% of", "to 42% of st.", "42% of st. finally", "st. finally a", "finally a minor", "a minor part also", "minor part also gets", "part also gets hydroxylated", "also gets hydroxylated by", "gets hydroxylated by cytochromes", "by cytochromes hutt", "cytochromes hutt et", "et al 1986", "al 1986 .", "in water aspirin acetylsalicylic", "water aspirin acetylsalicylic acid", "acid asa dissolves", "asa dissolves dissociating", "dissolves dissociating into the", "dissociating into the acetylsalicylate ion", "the acetylsalicylate ion asa", "ion asa .", ". asa is an", "asa is an anti", "is an anti clotting agent", "an anti clotting agent and", "anti clotting agent and nonsteroidal", "clotting agent and nonsteroidal anti", "agent and nonsteroidal anti inflammatory", "and nonsteroidal anti inflammatory drug", "anti inflammatory drug nsaid", "nsaid the therapeutic", "the therapeutic effects are mediated", "therapeutic effects are mediated through", "effects are mediated through its", "are mediated through its interaction", "mediated through its interaction with", "through its interaction with ptgs", "its interaction with ptgs enzymes.", "interaction with ptgs enzymes. on", "with ptgs enzymes. on a", "ptgs enzymes. on a molar", "enzymes. on a molar basis", "on a molar basis asa", "basis asa a", "a is more potent", "is more potent as an", "more potent as an analgesic/anti", "potent as an analgesic/anti inflammatory", "as an analgesic/anti inflammatory agent", "inflammatory agent b", "b has greater gastric", "has greater gastric ulcerogenic activity", "gastric ulcerogenic activity and", "activity and c", "and c is", "c is much more", "is much more effective as", "much more effective as an", "more effective as an inhibitor", "effective as an inhibitor of", "as an inhibitor of prostaglandin", "an inhibitor of prostaglandin biosynthesis", "inhibitor of prostaglandin biosynthesis and", "of prostaglandin biosynthesis and platelet", "prostaglandin biosynthesis and platelet aggregation", "biosynthesis and platelet aggregation than", "and platelet aggregation than salicylate", "aggregation than salicylate st", "st flower 1974", "flower 1974 mills et", "1974 mills et al", "mills et al 1974", "al 1974 rainsford", "rainsford 1975 rainsford 1977", "1975 rainsford 1977 .
              acetylsalicylic", "rainsford 1977 .
              acetylsalicylic acid is", "1977 .
              acetylsalicylic acid is only", ".
              acetylsalicylic acid is only slightly", "acid is only slightly soluble", "is only slightly soluble in", "only slightly soluble in conditions", "slightly soluble in conditions being", "soluble in conditions being found", "in conditions being found in", "conditions being found in the", "being found in the stomach", "found in the stomach mucosa", "the stomach mucosa mostly", "stomach mucosa mostly because", "mucosa mostly because of", "mostly because of unavailability of", "because of unavailability of sufficient", "of unavailability of sufficient amount", "unavailability of sufficient amount of", "of sufficient amount of solvent.", "sufficient amount of solvent. the", "amount of solvent. the absorption", "solvent. the absorption as", "the absorption as well", "absorption as well as", "as well as the absorbing", "well as the absorbing area", "the absorbing area increases", "absorbing area increases in", "area increases in the", "increases in the small intestine.", "in the small intestine. further", "the small intestine. further increased", "small intestine. further increased absorption", "intestine. further increased absorption is", "further increased absorption is achieved", "increased absorption is achieved by", "absorption is achieved by dissolving", "is achieved by dissolving tablets", "achieved by dissolving tablets before", "by dissolving tablets before ingestion", "dissolving tablets before ingestion or", "tablets before ingestion or usage", "before ingestion or usage of", "ingestion or usage of asa", "or usage of asa salts", "of asa salts dressman", "asa salts dressman et", "salts dressman et al", "dressman et al 2012", "et al 2012 .", "al 2012 . practically", "2012 . practically 100% of", ". practically 100% of therapeutic", "practically 100% of therapeutic aspirin", "100% of therapeutic aspirin doses", "of therapeutic aspirin doses are", "therapeutic aspirin doses are taken", "aspirin doses are taken up", "are taken up mostly", "taken up mostly by", "up mostly by intestinal", "mostly by intestinal mucosal cells", "intestinal mucosal cells artursson", "mucosal cells artursson &", "cells artursson & karlsson", "artursson & karlsson 1991", "karlsson 1991 yee", "1991 yee 1997 .
              only", "yee 1997 .
              only a few", "1997 .
              only a few percent", ".
              only a few percent of", "a few percent of asa", "percent of asa remain", "of asa remain unchanged", "remain unchanged the rest", "unchanged the rest is", "the rest is hydrolyzed to", "rest is hydrolyzed to salicylate", "hydrolyzed to salicylate st", "to salicylate st .", "salicylate st . the", "st . the major route", ". the major route of", "the major route of st", "major route of st catabolism", "route of st catabolism is", "of st catabolism is conjugation", "st catabolism is conjugation with", "catabolism is conjugation with glycine", "is conjugation with glycine to", "conjugation with glycine to form", "with glycine to form salicyluric", "glycine to form salicyluric acid.", "to form salicyluric acid. this", "form salicyluric acid. this accounts", "salicyluric acid. this accounts for", "acid. this accounts for 20\u201365%", "this accounts for 20\u201365% of", "accounts for 20\u201365% of the", "for 20\u201365% of the products.", "20\u201365% of the products. conjugation", "of the products. conjugation to", "the products. conjugation to glucuronides", "conjugation to glucuronides ester", "to glucuronides ester and", "glucuronides ester and ether", "ester and ether removes", "and ether removes up", "ether removes up to", "removes up to 42% of", "up to 42% of st.", "to 42% of st. finally", "of st. finally a", "st. finally a minor", "finally a minor part", "a minor part also gets", "minor part also gets hydroxylated", "part also gets hydroxylated by", "also gets hydroxylated by cytochromes", "hydroxylated by cytochromes hutt", "by cytochromes hutt et", "cytochromes hutt et al", "hutt et al 1986", "et al 1986 ." ] }, { "record_id": "GLY_000594_1_1878", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9753281", "r hsa", "hsa 9753281", "r hsa 9753281" ] }, { "record_id": "GLY_000594_1_1878", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "paracetamol adme", "aka acetaminophen", "acetaminophen or", "or n", "n acetyl", "acetyl p", "p aminophenol", "is an", "an analgesic", "analgesic drug", "drug used", "used for", "for to", "to treat", "treat mild", "mild to", "to moderate", "moderate pain", "pain and", "and as", "as an", "an antipyretic", "antipyretic agent.", "agent. it", "it is", "is one", "one of", "of the", "the most", "most widely", "widely used", "used drugs", "drugs in", "in the", "the world", "world and", "and is", "is available", "available alone", "alone or", "or in", "in combination", "combination with", "with other", "other drugs", "drugs for", "for pain", "pain relief", "fever and", "and allergy.", "allergy. it", "is thought", "thought to", "to act", "act through", "through the", "the inhibition", "inhibition of", "of cyclooxygenases", "cyclooxygenases 1", "1 and", "and 2", "graham et", "et al.", "al. 2013", "esh et", "al. 2021", "2021 .", ". paracetamol", "paracetamol is", "is generally", "generally safe", "safe at", "at therapeutic", "therapeutic doses", "doses but", "but in", "in overdose", "overdose cases", "it causes", "causes mitochondrial", "mitochondrial dysfunction", "dysfunction and", "and centrilobular", "centrilobular necrosis", "necrosis in", "the liver", "liver which", "which can", "can lead", "lead to", "to death.

              apap", "death.

              apap has", "has a", "a high", "high oral", "oral bioavailability", "is well", "well absorbed", "absorbed and", "and reaches", "reaches peak", "peak blood", "blood concentrations", "concentrations after", "after 90", "90 minutes", "minutes after", "after ingestion.", "ingestion. apap", "apap binds", "binds plasma", "plasma proteins", "proteins to", "to a", "a small", "small extent", "extent and", "and has", "a plasma", "plasma half", "half life", "life of", "of 1.5", "1.5 3", "3 hours.", "hours. most", "most of", "the drug", "drug is", "is eliminated", "eliminated by", "by glucuronidate", "glucuronidate and", "and sulfate", "sulfate conjugation", "~55% and", "and ~30%", "~30% respectively", "liver or", "or as", "as unchanged", "unchanged drug", "forrest et", "al. 1982", "1982 .", ". a", "small amount", "5 15%", "is oxidised", "oxidised to", "to the", "the reactive", "reactive metabolite", "metabolite n", "acetyl para", "para benzoquinone", "benzoquinone imine", "napqi .", ". napqi", "napqi is", "is usually", "usually detoxified", "detoxified by", "by binding", "binding to", "to liver", "liver glutathione", "glutathione but", "glutathione is", "is depleted", "depleted and", "and napqi", "napqi instead", "binds to", "to sulfhydryl", "sulfhydryl groups", "groups on", "on proteins", "leading to", "liver damage.", "damage. abcc2", "abcc4 and", "and abcg2", "abcg2 transporters", "transporters mediate", "mediate the", "the efflux", "efflux of", "of apap", "apap metabolites", "metabolites out", "out of", "of cells", "mcgill &", "& jaeschke", "jaeschke 2013", "2013 .", "paracetamol apap", "apap aka", "aka acetaminophen or", "acetaminophen or n", "or n acetyl", "n acetyl p", "acetyl p aminophenol", "aminophenol is", "is an analgesic", "an analgesic drug", "analgesic drug used", "drug used for", "used for to", "for to treat", "to treat mild", "treat mild to", "mild to moderate", "to moderate pain", "moderate pain and", "pain and as", "and as an", "as an antipyretic", "an antipyretic agent.", "antipyretic agent. it", "agent. it is", "it is one", "is one of", "one of the", "of the most", "the most widely", "most widely used", "widely used drugs", "used drugs in", "drugs in the", "in the world", "the world and", "world and is", "and is available", "is available alone", "available alone or", "alone or in", "or in combination", "in combination with", "combination with other", "with other drugs", "other drugs for", "drugs for pain", "for pain relief", "relief fever", "fever and allergy.", "and allergy. it", "allergy. it is", "it is thought", "is thought to", "thought to act", "to act through", "act through the", "through the inhibition", "the inhibition of", "inhibition of cyclooxygenases", "of cyclooxygenases 1", "cyclooxygenases 1 and", "1 and 2", "2 graham", "graham et al.", "et al. 2013", "2013 esh", "esh et al.", "et al. 2021", "al. 2021 .", "2021 . paracetamol", ". paracetamol is", "paracetamol is generally", "is generally safe", "generally safe at", "safe at therapeutic", "at therapeutic doses", "therapeutic doses but", "doses but in", "but in overdose", "in overdose cases", "cases it", "it causes mitochondrial", "causes mitochondrial dysfunction", "mitochondrial dysfunction and", "dysfunction and centrilobular", "and centrilobular necrosis", "centrilobular necrosis in", "necrosis in the", "in the liver", "the liver which", "liver which can", "which can lead", "can lead to", "lead to death.

              apap", "to death.

              apap has", "death.

              apap has a", "has a high", "a high oral", "high oral bioavailability", "bioavailability ~88%", "is well absorbed", "well absorbed and", "absorbed and reaches", "and reaches peak", "reaches peak blood", "peak blood concentrations", "blood concentrations after", "concentrations after 90", "after 90 minutes", "90 minutes after", "minutes after ingestion.", "after ingestion. apap", "ingestion. apap binds", "apap binds plasma", "binds plasma proteins", "plasma proteins to", "proteins to a", "to a small", "a small extent", "small extent and", "extent and has", "and has a", "has a plasma", "a plasma half", "plasma half life", "half life of", "life of 1.5", "of 1.5 3", "1.5 3 hours.", "3 hours. most", "hours. most of", "most of the", "of the drug", "the drug is", "drug is eliminated", "is eliminated by", "eliminated by glucuronidate", "by glucuronidate and", "glucuronidate and sulfate", "and sulfate conjugation", "conjugation ~55%", "~55% and ~30%", "and ~30% respectively", "respectively in", "the liver or", "liver or as", "or as unchanged", "as unchanged drug", "drug ~5%", "forrest et al.", "et al. 1982", "al. 1982 .", "1982 . a", ". a small", "a small amount", "amount 5", "15% is", "is oxidised to", "oxidised to the", "to the reactive", "the reactive metabolite", "reactive metabolite n", "metabolite n acetyl", "n acetyl para", "acetyl para benzoquinone", "para benzoquinone imine", "imine napqi", "napqi . napqi", ". napqi is", "napqi is usually", "is usually detoxified", "usually detoxified by", "detoxified by binding", "by binding to", "binding to liver", "to liver glutathione", "liver glutathione but", "glutathione but in", "cases glutathione", "glutathione is depleted", "is depleted and", "depleted and napqi", "and napqi instead", "instead binds", "binds to sulfhydryl", "to sulfhydryl groups", "sulfhydryl groups on", "groups on proteins", "proteins leading", "leading to liver", "to liver damage.", "liver damage. abcc2", "abcc2 abcc3", "abcc3 abcc4", "abcc4 and abcg2", "and abcg2 transporters", "abcg2 transporters mediate", "transporters mediate the", "mediate the efflux", "the efflux of", "efflux of apap", "of apap metabolites", "apap metabolites out", "metabolites out of", "out of cells", "cells mcgill", "mcgill & jaeschke", "& jaeschke 2013", "jaeschke 2013 .", "apap aka acetaminophen", "aka acetaminophen or n", "acetaminophen or n acetyl", "or n acetyl p", "n acetyl p aminophenol", "p aminophenol is", "aminophenol is an", "is an analgesic drug", "an analgesic drug used", "analgesic drug used for", "drug used for to", "used for to treat", "for to treat mild", "to treat mild to", "treat mild to moderate", "mild to moderate pain", "to moderate pain and", "moderate pain and as", "pain and as an", "and as an antipyretic", "as an antipyretic agent.", "an antipyretic agent. it", "antipyretic agent. it is", "agent. it is one", "it is one of", "is one of the", "one of the most", "of the most widely", "the most widely used", "most widely used drugs", "widely used drugs in", "used drugs in the", "drugs in the world", "in the world and", "the world and is", "world and is available", "and is available alone", "is available alone or", "available alone or in", "alone or in combination", "or in combination with", "in combination with other", "combination with other drugs", "with other drugs for", "other drugs for pain", "drugs for pain relief", "pain relief fever", "relief fever and", "fever and allergy. it", "and allergy. it is", "allergy. it is thought", "it is thought to", "is thought to act", "thought to act through", "to act through the", "act through the inhibition", "through the inhibition of", "the inhibition of cyclooxygenases", "inhibition of cyclooxygenases 1", "of cyclooxygenases 1 and", "cyclooxygenases 1 and 2", "and 2 graham", "2 graham et", "graham et al. 2013", "al. 2013 esh", "2013 esh et", "esh et al. 2021", "et al. 2021 .", "al. 2021 . paracetamol", "2021 . paracetamol is", ". paracetamol is generally", "paracetamol is generally safe", "is generally safe at", "generally safe at therapeutic", "safe at therapeutic doses", "at therapeutic doses but", "therapeutic doses but in", "doses but in overdose", "but in overdose cases", "overdose cases it", "cases it causes", "it causes mitochondrial dysfunction", "causes mitochondrial dysfunction and", "mitochondrial dysfunction and centrilobular", "dysfunction and centrilobular necrosis", "and centrilobular necrosis in", "centrilobular necrosis in the", "necrosis in the liver", "in the liver which", "the liver which can", "liver which can lead", "which can lead to", "can lead to death.

              apap", "lead to death.

              apap has", "to death.

              apap has a", "death.

              apap has a high", "has a high oral", "a high oral bioavailability", "oral bioavailability ~88%", "~88% is", "is well absorbed and", "well absorbed and reaches", "absorbed and reaches peak", "and reaches peak blood", "reaches peak blood concentrations", "peak blood concentrations after", "blood concentrations after 90", "concentrations after 90 minutes", "after 90 minutes after", "90 minutes after ingestion.", "minutes after ingestion. apap", "after ingestion. apap binds", "ingestion. apap binds plasma", "apap binds plasma proteins", "binds plasma proteins to", "plasma proteins to a", "proteins to a small", "to a small extent", "a small extent and", "small extent and has", "extent and has a", "and has a plasma", "has a plasma half", "a plasma half life", "plasma half life of", "half life of 1.5", "life of 1.5 3", "of 1.5 3 hours.", "1.5 3 hours. most", "3 hours. most of", "hours. most of the", "most of the drug", "of the drug is", "the drug is eliminated", "drug is eliminated by", "is eliminated by glucuronidate", "eliminated by glucuronidate and", "by glucuronidate and sulfate", "glucuronidate and sulfate conjugation", "sulfate conjugation ~55%", "conjugation ~55% and", "~55% and ~30% respectively", "~30% respectively in", "respectively in the", "in the liver or", "the liver or as", "liver or as unchanged", "or as unchanged drug", "unchanged drug ~5%", "~5% forrest", "forrest et al. 1982", "et al. 1982 .", "al. 1982 . a", "1982 . a small", ". a small amount", "small amount 5", "amount 5 15%", "5 15% is", "15% is oxidised", "is oxidised to the", "oxidised to the reactive", "to the reactive metabolite", "the reactive metabolite n", "reactive metabolite n acetyl", "metabolite n acetyl para", "n acetyl para benzoquinone", "acetyl para benzoquinone imine", "benzoquinone imine napqi", "imine napqi .", "napqi . napqi is", ". napqi is usually", "napqi is usually detoxified", "is usually detoxified by", "usually detoxified by binding", "detoxified by binding to", "by binding to liver", "binding to liver glutathione", "to liver glutathione but", "liver glutathione but in", "glutathione but in overdose", "overdose cases glutathione", "cases glutathione is", "glutathione is depleted and", "is depleted and napqi", "depleted and napqi instead", "napqi instead binds", "instead binds to", "binds to sulfhydryl groups", "to sulfhydryl groups on", "sulfhydryl groups on proteins", "on proteins leading", "proteins leading to", "leading to liver damage.", "to liver damage. abcc2", "damage. abcc2 abcc3", "abcc3 abcc4 and", "abcc4 and abcg2 transporters", "and abcg2 transporters mediate", "abcg2 transporters mediate the", "transporters mediate the efflux", "mediate the efflux of", "the efflux of apap", "efflux of apap metabolites", "of apap metabolites out", "apap metabolites out of", "metabolites out of cells", "of cells mcgill", "cells mcgill &", "mcgill & jaeschke 2013", "& jaeschke 2013 .", "paracetamol apap aka", "apap aka acetaminophen or", "aka acetaminophen or n acetyl", "acetaminophen or n acetyl p", "or n acetyl p aminophenol", "acetyl p aminophenol is", "p aminophenol is an", "aminophenol is an analgesic", "is an analgesic drug used", "an analgesic drug used for", "analgesic drug used for to", "drug used for to treat", "used for to treat mild", "for to treat mild to", "to treat mild to moderate", "treat mild to moderate pain", "mild to moderate pain and", "to moderate pain and as", "moderate pain and as an", "pain and as an antipyretic", "and as an antipyretic agent.", "as an antipyretic agent. it", "an antipyretic agent. it is", "antipyretic agent. it is one", "agent. it is one of", "it is one of the", "is one of the most", "one of the most widely", "of the most widely used", "the most widely used drugs", "most widely used drugs in", "widely used drugs in the", "used drugs in the world", "drugs in the world and", "in the world and is", "the world and is available", "world and is available alone", "and is available alone or", "is available alone or in", "available alone or in combination", "alone or in combination with", "or in combination with other", "in combination with other drugs", "combination with other drugs for", "with other drugs for pain", "other drugs for pain relief", "for pain relief fever", "pain relief fever and", "relief fever and allergy.", "fever and allergy. it is", "and allergy. it is thought", "allergy. it is thought to", "it is thought to act", "is thought to act through", "thought to act through the", "to act through the inhibition", "act through the inhibition of", "through the inhibition of cyclooxygenases", "the inhibition of cyclooxygenases 1", "inhibition of cyclooxygenases 1 and", "of cyclooxygenases 1 and 2", "1 and 2 graham", "and 2 graham et", "2 graham et al.", "et al. 2013 esh", "al. 2013 esh et", "2013 esh et al.", "esh et al. 2021 .", "et al. 2021 . paracetamol", "al. 2021 . paracetamol is", "2021 . paracetamol is generally", ". paracetamol is generally safe", "paracetamol is generally safe at", "is generally safe at therapeutic", "generally safe at therapeutic doses", "safe at therapeutic doses but", "at therapeutic doses but in", "therapeutic doses but in overdose", "doses but in overdose cases", "in overdose cases it", "overdose cases it causes", "cases it causes mitochondrial", "it causes mitochondrial dysfunction and", "causes mitochondrial dysfunction and centrilobular", "mitochondrial dysfunction and centrilobular necrosis", "dysfunction and centrilobular necrosis in", "and centrilobular necrosis in the", "centrilobular necrosis in the liver", "necrosis in the liver which", "in the liver which can", "the liver which can lead", "liver which can lead to", "which can lead to death.

              apap", "can lead to death.

              apap has", "lead to death.

              apap has a", "to death.

              apap has a high", "death.

              apap has a high oral", "has a high oral bioavailability", "high oral bioavailability ~88%", "~88% is well", "is well absorbed and reaches", "well absorbed and reaches peak", "absorbed and reaches peak blood", "and reaches peak blood concentrations", "reaches peak blood concentrations after", "peak blood concentrations after 90", "blood concentrations after 90 minutes", "concentrations after 90 minutes after", "after 90 minutes after ingestion.", "90 minutes after ingestion. apap", "minutes after ingestion. apap binds", "after ingestion. apap binds plasma", "ingestion. apap binds plasma proteins", "apap binds plasma proteins to", "binds plasma proteins to a", "plasma proteins to a small", "proteins to a small extent", "to a small extent and", "a small extent and has", "small extent and has a", "extent and has a plasma", "and has a plasma half", "has a plasma half life", "a plasma half life of", "plasma half life of 1.5", "half life of 1.5 3", "life of 1.5 3 hours.", "of 1.5 3 hours. most", "1.5 3 hours. most of", "3 hours. most of the", "hours. most of the drug", "most of the drug is", "of the drug is eliminated", "the drug is eliminated by", "drug is eliminated by glucuronidate", "is eliminated by glucuronidate and", "eliminated by glucuronidate and sulfate", "by glucuronidate and sulfate conjugation", "and sulfate conjugation ~55%", "sulfate conjugation ~55% and", "conjugation ~55% and ~30%", "and ~30% respectively in", "~30% respectively in the", "respectively in the liver", "in the liver or as", "the liver or as unchanged", "liver or as unchanged drug", "as unchanged drug ~5%", "~5% forrest et", "forrest et al. 1982 .", "et al. 1982 . a", "al. 1982 . a small", "1982 . a small amount", "a small amount 5", "small amount 5 15%", "5 15% is oxidised", "15% is oxidised to", "is oxidised to the reactive", "oxidised to the reactive metabolite", "to the reactive metabolite n", "the reactive metabolite n acetyl", "reactive metabolite n acetyl para", "metabolite n acetyl para benzoquinone", "n acetyl para benzoquinone imine", "para benzoquinone imine napqi", "benzoquinone imine napqi .", "imine napqi . napqi", "napqi . napqi is usually", ". napqi is usually detoxified", "napqi is usually detoxified by", "is usually detoxified by binding", "usually detoxified by binding to", "detoxified by binding to liver", "by binding to liver glutathione", "binding to liver glutathione but", "to liver glutathione but in", "liver glutathione but in overdose", "glutathione but in overdose cases", "in overdose cases glutathione", "overdose cases glutathione is", "cases glutathione is depleted", "glutathione is depleted and napqi", "is depleted and napqi instead", "and napqi instead binds", "napqi instead binds to", "instead binds to sulfhydryl", "binds to sulfhydryl groups on", "to sulfhydryl groups on proteins", "groups on proteins leading", "on proteins leading to", "proteins leading to liver", "leading to liver damage. abcc2", "liver damage. abcc2 abcc3", "abcc2 abcc3 abcc4", "abcc3 abcc4 and abcg2", "abcc4 and abcg2 transporters mediate", "and abcg2 transporters mediate the", "abcg2 transporters mediate the efflux", "transporters mediate the efflux of", "mediate the efflux of apap", "the efflux of apap metabolites", "efflux of apap metabolites out", "of apap metabolites out of", "apap metabolites out of cells", "out of cells mcgill", "of cells mcgill &", "cells mcgill & jaeschke", "mcgill & jaeschke 2013 ." ] }, { "record_id": "GLY_000594_1_1879", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9754189", "r hsa", "hsa 9754189", "r hsa 9754189" ] }, { "record_id": "GLY_000594_1_1879", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "germ layer", "layer formation", "formation at", "at gastrulation", "germ layer formation", "layer formation at", "formation at gastrulation", "germ layer formation at", "layer formation at gastrulation", "germ layer formation at gastrulation", "due to", "to ethical", "ethical considerations", "most research", "research on", "on mammalian", "mammalian gastrulation", "gastrulation has", "has been", "been performed", "performed on", "on mouse", "mouse embryos.", "embryos. therefore", "therefore most", "most of", "of the", "the reactions", "reactions described", "described in", "in this", "this section", "section are", "are the", "the results", "results of", "of research", "research in", "in mouse", "embryos. significant", "significant research", "research has", "has also", "also been", "on non", "non human", "human primates", "primates such", "such as", "as cynomolgus", "cynomolgus monkeys", "macaca fascicularis", "nakamura et", "et al.", "al. 2016", "sasaki et", "2016 .", ". more", "more recently", "human gastrula", "gastrula like", "like cell", "cell assemblages", "generated from", "from pluripotent", "pluripotent stem", "stem cells", "cells have", "have been", "been developed", "moris et", "al. 2020", "and are", "are now", "now being", "being compared", "compared with", "with mouse", "mouse embryos", "reviewed in", "in rossant", "rossant and", "and tam", "tam 2021", "ghimire et", "al. 2021", "2021 .
              at", ".
              at the", "the beginning", "beginning of", "of gastrulation", "gastrulation in", "in the", "the mouse", "the primitive", "primitive streak", "streak forms", "forms in", "in a", "a region", "region of", "of bmp", "and nodal", "nodal signaling.", "signaling. in", "mouse embryo", "nodal is", "is expressed", "expressed throughout", "throughout the", "the epiblast", "epiblast before", "before anterior", "anterior posterior", "posterior axis", "axis induction", "induction and", "and is", "is required", "required for", "for pluripotency", "in robertson", "robertson 2014", "2014 .", ". nodal", "nodal signaling", "signaling is", "is restricted", "restricted to", "to the", "the posterior", "posterior side", "side of", "the embryo", "embryo by", "by the", "the secretion", "secretion of", "of nodal", "nodal and", "and wnt", "wnt antagonists", "from the", "the anterior", "anterior visceral", "visceral endoderm", "in stower", "stower and", "and srinivas", "srinivas 2014", "in human", "human embryonic", "embryonic stem", "is also", "also crucial", "crucial for", "for maintenance", "maintenance of", "of pluripotency", "james et", "al. 2005", "vallier et", "al. 2004", "2004 .", ". in", "and wnt3", "wnt3 are", "are required", "for formation", "formation of", "conlon et", "al. 1994", "brennan et", "al. 2001", "liu et", "al. 1999", "nodal expression", "expression subsequently", "subsequently becomes", "becomes restricted", "the node", "node at", "at the", "anterior end", "end of", "zhou et", "al. 1993", "1993 .", ". pro", "pro nodal", "nodal secreted", "secreted by", "epiblast in", "in response", "response to", "to bmp4", "bmp4 signalling", "signalling from", "the extraembryonic", "extraembryonic ectoderm", "ectoderm is", "is converted", "converted to", "to mature", "mature nodal", "nodal by", "by furin", "secreted from", "extraembryonic ectoderm.", "ectoderm. nodal", "nodal maintains", "maintains bmp4", "bmp4 expression", "expression in", "ectoderm which", "which then", "then activates", "activates wnt3", "wnt3 in", "posterior epiblast.", "epiblast. wnt", "wnt signaling", "in turn", "amplifies nodal", "2001 .", ". the", "the order", "order of", "of events", "events in", "this signaling", "signaling cascade", "cascade may", "may be", "be different", "different in", "human embryos", "embryos due", "to differences", "differences in", "in early", "early embryo", "embryo architecture.
              nodal", "wnt show", "show similar", "similar effects", "effects on", "on human", "human 2d", "2d gastruloids", "martyn et", "al. 2019", "2019 .", ". mesoderm", "mesoderm and", "and definitive", "definitive endoderm", "endoderm progenitors", "progenitors appear", "appear to", "to be", "be already", "already separate", "separate and", "and distinct", "distinct in", "therefore bipotential", "bipotential mesendoderm", "mesendoderm progenitors", "progenitors may", "be transitory", "transitory if", "if they", "they exist", "probst et", "2021 .", ". this", "this is", "is an", "an area", "area of", "of ongoing", "ongoing research.
              mesoderm", "research.
              mesoderm is", "is formed", "formed by", "by an", "an epithelial", "epithelial mesenchymal", "mesenchymal transition", "transition that", "that produces", "produces an", "an ingression", "ingression of", "of cells", "cells through", "through the", "primitive streak.", "streak. endoderm", "endoderm does", "does not", "not show", "show a", "a complete", "complete epithelial", "transition and", "and instead", "instead forms", "forms by", "by cell", "cell plasticity", "a partial", "partial epithelial", "transition in", "in which", "which both", "both e", "e cadherin", "cadherin and", "and n", "n cadherin", "cadherin are", "are expressed", "inferred from", "from mouse", "embryos in", "in scheibner", "scheibner et", ". however", "embryos endoderm", "progenitors still", "still ingress", "ingress through", "anterior region", "migrate with", "with mesoderm", "mesoderm cells", "and eventually", "eventually integrate", "integrate into", "into the", "the visceral", "endoderm layer", "layer to", "to give", "give rise", "rise to", "the definitive", "viotti et", "al. 2014", "2014 .
              specific", ".
              specific types", "types of", "of mesoderm", "mesoderm are", "are formed", "formed sequentially", "sequentially according", "according to", "the time", "time and", "and position", "position of", "of ingression", "streak. this", "this patterning", "patterning is", "is caused", "caused by", "by gradients", "gradients of", "and bmp", "bmp signaling", "signaling that", "that activate", "activate transcriptional", "transcriptional programs", "programs in", "the mesoderm", "mesoderm progenitors.
              t", "progenitors.
              t box", "box transcription", "transcription factor", "factor t", "and eomesodermin", "are two", "two of", "the first", "first transcription", "transcription factors", "factors expressed", "expressed in", "in mesoderm", "and endoderm", "progenitors in", "in probst", "probst and", "and arnold", "arnold 2016", "the two", "two factors", "factors combined", "combined are", "of all", "all mesoderm", "arnold et", "al. 2008", "tosic et", "2019 .
              tbxt", ".
              tbxt is", "is activated", "activated by", "by wnt", "via beta", "beta catenin", "catenin acting", "acting with", "with lef1", "lef1 or", "or tcf1", "and bmp4", "bmp4 and", "in mesodermal", "mesodermal and", "and axial", "axial mesodermal", "mesodermal progenitors", "progenitors and", "and in", "streak during", "during gastrulation", "later becoming", "becoming localized", "localized to", "the notochord", "notochord and", "and tailbud.", "tailbud. tbxt", "tbxt is", "an early", "early marker", "marker of", "of mesodermal", "mesodermal differentiation", "differentiation and", "is often", "often used", "used in", "in studies", "studies of", "of embryonic", "stem cells.", "cells. in", "in hescs", "hescs tbxt", "in both", "both mesodermal", "and endodermal", "endodermal progenitors", "it regulates", "regulates different", "different sets", "sets of", "of target", "target genes", "genes depending", "depending on", "on the", "the signaling", "signaling environment", "faial et", "al. 2015", "2015 .
              expression", ".
              expression of", "of eomes", "eomes is", "by nodal", "nodal via", "via smad2", "smad2 and", "and smad3", "smad3 and", "is observed", "observed in", "posterior epiblast", "epiblast prior", "prior to", "to formation", "streak and", "progenitors during", "during the", "first day", "day of", "of gastrulation.", "gastrulation. eomes", "eomes in", "in combination", "combination with", "with smad2", "smad2 3", "3 is", "is crucial", "for the", "the activation", "activation of", "of definitive", "endoderm genes", "teo et", "al. 2011", "2011 .", ". tbxt", "tbxt and", "and eomes", "eomes generally", "generally activate", "activate expression", "expression of", "mesoderm genes", "genes and", "and repress", "repress expression", "of genes", "genes associated", "associated with", "with pluripotency", "pluripotency such", "as sox2", "sox2 and", "and nanog.
              some", "nanog.
              some transcription", "factors are", "are particularly", "particularly important", "important for", "for regulating", "regulating gastrulation", "gastrulation and", "are also", "also used", "used as", "as markers", "markers for", "for particular", "particular stages", "stages and", "and morphological", "morphological features.", "features. for", "for example", "expression marks", "marks the", "the onset", "onset of", "is first", "first observed", "and becomes", "becomes localized", "and then", "then the", "the axial", "axial mesoderm", "blum et", "al. 1992", "1992 .", ". smad2", "smad3 activated", "nodal are", "are recruited", "recruited to", "the gsc", "gsc promoter", "promoter by", "by foxh1", "which is", "is already", "already located", "located at", "the promoter.", "promoter. mixl1", "mixl1 also", "also binds", "binds the", "promoter and", "and activates", "activates expression.", "expression. in", "in mice", "gsc is", "is a", "a regulator", "regulator of", "of head", "head development.
              mixl1", "development.
              mixl1 is", "of both", "both mesoderm", "hart et", "al. 2002", "expressed early", "early throughout", "in nascent", "nascent mesoderm", "cells exiting", "exiting the", "the streak.", "streak. expression", "of mixl1", "mixl1 is", "is mediated", "mediated downstream", "downstream by", "nodal through", "through smad2", "smad3 binding", "binding to", "the promoter", "promoter of", "of mixl1.", "mixl1. eomes", "eomes also", "also plays", "plays a", "a direct", "direct role", "role in", "in activating", "activating mixl1", "mixl1 and", "and gsc", "gsc expression", "2019 ..
              developing", "..
              developing mesoderm", "mesoderm becomes", "becomes specified", "specified by", "by expression", "of transcription", "factors such", "as mesp1", "a marker", "of cardiac", "cardiac progenitors.", "see the", "the reactome", "reactome pathway", "pathway \\cardiogenesis\\.", "due to ethical", "to ethical considerations", "considerations most", "most research on", "research on mammalian", "on mammalian gastrulation", "mammalian gastrulation has", "gastrulation has been", "has been performed", "been performed on", "performed on mouse", "on mouse embryos.", "mouse embryos. therefore", "embryos. therefore most", "therefore most of", "most of the", "of the reactions", "the reactions described", "reactions described in", "described in this", "in this section", "this section are", "section are the", "are the results", "the results of", "results of research", "of research in", "research in mouse", "in mouse embryos.", "mouse embryos. significant", "embryos. significant research", "significant research has", "research has also", "has also been", "also been performed", "performed on non", "on non human", "non human primates", "human primates such", "primates such as", "such as cynomolgus", "as cynomolgus monkeys", "monkeys macaca", "nakamura et al.", "et al. 2016", "2016 sasaki", "sasaki et al.", "al. 2016 .", "2016 . more", ". more recently", "recently human", "human gastrula like", "gastrula like cell", "like cell assemblages", "assemblages \\gastruloids\\", "\\gastruloids\\ generated", "generated from pluripotent", "from pluripotent stem", "pluripotent stem cells", "stem cells have", "cells have been", "have been developed", "developed moris", "moris et al.", "et al. 2020", "2020 and", "and are now", "are now being", "now being compared", "being compared with", "compared with mouse", "with mouse embryos", "embryos reviewed", "reviewed in rossant", "in rossant and", "rossant and tam", "and tam 2021", "2021 ghimire", "ghimire et al.", "et al. 2021", "al. 2021 .
              at", "2021 .
              at the", ".
              at the beginning", "the beginning of", "beginning of gastrulation", "of gastrulation in", "gastrulation in the", "in the mouse", "mouse the", "the primitive streak", "primitive streak forms", "streak forms in", "forms in a", "in a region", "a region of", "region of bmp", "bmp wnt", "wnt fgf", "fgf and", "and nodal signaling.", "nodal signaling. in", "signaling. in the", "the mouse embryo", "embryo nodal", "nodal is expressed", "is expressed throughout", "expressed throughout the", "throughout the epiblast", "the epiblast before", "epiblast before anterior", "before anterior posterior", "anterior posterior axis", "posterior axis induction", "axis induction and", "induction and is", "and is required", "is required for", "required for pluripotency", "pluripotency reviewed", "reviewed in robertson", "in robertson 2014", "robertson 2014 .", "2014 . nodal", ". nodal signaling", "nodal signaling is", "signaling is restricted", "is restricted to", "restricted to the", "to the posterior", "the posterior side", "posterior side of", "side of the", "of the embryo", "the embryo by", "embryo by the", "by the secretion", "the secretion of", "secretion of nodal", "of nodal and", "nodal and wnt", "and wnt antagonists", "antagonists cer1", "cer1 lefty1", "lefty1 from", "from the anterior", "the anterior visceral", "anterior visceral endoderm", "endoderm ave", "reviewed in stower", "in stower and", "stower and srinivas", "and srinivas 2014", "srinivas 2014 .", "in human embryonic", "human embryonic stem", "embryonic stem cells", "cells hescs", "hescs nodal", "nodal is also", "is also crucial", "also crucial for", "crucial for maintenance", "for maintenance of", "maintenance of pluripotency", "pluripotency james", "james et al.", "et al. 2005", "2005 vallier", "vallier et al.", "et al. 2004", "al. 2004 .", "2004 . in", ". in mouse", "in mouse embryos", "embryos nodal", "nodal and wnt3", "and wnt3 are", "wnt3 are required", "are required for", "required for formation", "for formation of", "formation of the", "of the primitive", "streak conlon", "conlon et al.", "et al. 1994", "1994 brennan", "brennan et al.", "et al. 2001", "2001 liu", "liu et al.", "et al. 1999", "1999 and", "and nodal expression", "nodal expression subsequently", "expression subsequently becomes", "subsequently becomes restricted", "becomes restricted to", "to the node", "the node at", "node at the", "at the anterior", "the anterior end", "anterior end of", "end of the", "streak zhou", "zhou et al.", "et al. 1993", "al. 1993 .", "1993 . pro", ". pro nodal", "pro nodal secreted", "nodal secreted by", "secreted by the", "by the epiblast", "the epiblast in", "epiblast in response", "in response to", "response to bmp4", "to bmp4 signalling", "bmp4 signalling from", "signalling from the", "from the extraembryonic", "the extraembryonic ectoderm", "extraembryonic ectoderm is", "ectoderm is converted", "is converted to", "converted to mature", "to mature nodal", "mature nodal by", "nodal by furin", "furin pcsk3", "pcsk3 secreted", "secreted from the", "the extraembryonic ectoderm.", "extraembryonic ectoderm. nodal", "ectoderm. nodal maintains", "nodal maintains bmp4", "maintains bmp4 expression", "bmp4 expression in", "expression in the", "in the extraembryonic", "extraembryonic ectoderm which", "ectoderm which then", "which then activates", "then activates wnt3", "activates wnt3 in", "wnt3 in the", "in the posterior", "the posterior epiblast.", "posterior epiblast. wnt", "epiblast. wnt signaling", "signaling in", "turn amplifies", "amplifies nodal expression", "expression brennan", "al. 2001 .", "2001 . the", ". the order", "the order of", "order of events", "of events in", "events in this", "in this signaling", "this signaling cascade", "signaling cascade may", "cascade may be", "may be different", "be different in", "different in human", "in human embryos", "human embryos due", "embryos due to", "due to differences", "to differences in", "differences in early", "in early embryo", "early embryo architecture.
              nodal", "architecture.
              nodal bmp", "bmp and", "and wnt show", "wnt show similar", "show similar effects", "similar effects on", "effects on human", "on human 2d", "human 2d gastruloids", "gastruloids martyn", "martyn et al.", "et al. 2019", "al. 2019 .", "2019 . mesoderm", ". mesoderm and", "mesoderm and definitive", "and definitive endoderm", "definitive endoderm progenitors", "endoderm progenitors appear", "progenitors appear to", "appear to be", "to be already", "be already separate", "already separate and", "separate and distinct", "and distinct in", "distinct in the", "in the primitive", "streak therefore", "therefore bipotential mesendoderm", "bipotential mesendoderm progenitors", "mesendoderm progenitors may", "progenitors may be", "may be transitory", "be transitory if", "transitory if they", "if they exist", "exist probst", "probst et al.", "al. 2021 .", "2021 . this", ". this is", "this is an", "is an area", "an area of", "area of ongoing", "of ongoing research.
              mesoderm", "ongoing research.
              mesoderm is", "research.
              mesoderm is formed", "is formed by", "formed by an", "by an epithelial", "an epithelial mesenchymal", "epithelial mesenchymal transition", "mesenchymal transition that", "transition that produces", "that produces an", "produces an ingression", "an ingression of", "ingression of cells", "of cells through", "cells through the", "through the primitive", "the primitive streak.", "primitive streak. endoderm", "streak. endoderm does", "endoderm does not", "does not show", "not show a", "show a complete", "a complete epithelial", "complete epithelial mesenchymal", "mesenchymal transition and", "transition and instead", "and instead forms", "instead forms by", "forms by cell", "by cell plasticity", "plasticity a", "a partial epithelial", "partial epithelial mesenchymal", "mesenchymal transition in", "transition in which", "in which both", "which both e", "both e cadherin", "e cadherin and", "cadherin and n", "and n cadherin", "n cadherin are", "cadherin are expressed", "inferred from mouse", "from mouse embryos", "mouse embryos in", "embryos in scheibner", "in scheibner et", "scheibner et al.", "2021 . however", "however in", "mouse embryos endoderm", "embryos endoderm progenitors", "endoderm progenitors still", "progenitors still ingress", "still ingress through", "ingress through the", "through the anterior", "the anterior region", "anterior region of", "region of the", "streak migrate", "migrate with mesoderm", "with mesoderm cells", "cells and", "and eventually integrate", "eventually integrate into", "integrate into the", "into the visceral", "the visceral endoderm", "visceral endoderm layer", "endoderm layer to", "layer to give", "to give rise", "give rise to", "rise to the", "to the definitive", "the definitive endoderm", "endoderm viotti", "viotti et al.", "et al. 2014", "al. 2014 .
              specific", "2014 .
              specific types", ".
              specific types of", "types of mesoderm", "of mesoderm are", "mesoderm are formed", "are formed sequentially", "formed sequentially according", "sequentially according to", "according to the", "to the time", "the time and", "time and position", "and position of", "position of ingression", "of ingression of", "primitive streak. this", "streak. this patterning", "this patterning is", "patterning is caused", "is caused by", "caused by gradients", "by gradients of", "gradients of nodal", "nodal wnt", "wnt and", "and bmp signaling", "bmp signaling that", "signaling that activate", "that activate transcriptional", "activate transcriptional programs", "transcriptional programs in", "programs in the", "in the mesoderm", "the mesoderm progenitors.
              t", "mesoderm progenitors.
              t box", "progenitors.
              t box transcription", "box transcription factor", "transcription factor t", "t tbxt", "tbxt t", "t brachyury", "brachyury and", "eomesodermin eomes", "eomes are", "are two of", "two of the", "of the first", "the first transcription", "first transcription factors", "transcription factors expressed", "factors expressed in", "expressed in mesoderm", "in mesoderm and", "mesoderm and endoderm", "and endoderm progenitors", "endoderm progenitors in", "progenitors in the", "streak reviewed", "reviewed in probst", "in probst and", "probst and arnold", "and arnold 2016", "arnold 2016 .", "2016 . the", ". the two", "the two factors", "two factors combined", "factors combined are", "combined are required", "formation of all", "of all mesoderm", "all mesoderm and", "endoderm arnold", "arnold et al.", "et al. 2008", "2008 tosic", "tosic et al.", "al. 2019 .
              tbxt", "2019 .
              tbxt is", ".
              tbxt is activated", "is activated by", "activated by wnt", "by wnt signaling", "signaling via", "via beta catenin", "beta catenin acting", "catenin acting with", "acting with lef1", "with lef1 or", "lef1 or tcf1", "tcf1 and", "and bmp4 and", "bmp4 and is", "and is expressed", "is expressed in", "expressed in mesodermal", "in mesodermal and", "mesodermal and axial", "and axial mesodermal", "axial mesodermal progenitors", "mesodermal progenitors and", "progenitors and in", "and in the", "primitive streak during", "streak during gastrulation", "gastrulation later", "later becoming localized", "becoming localized to", "localized to the", "to the notochord", "the notochord and", "notochord and tailbud.", "and tailbud. tbxt", "tailbud. tbxt is", "tbxt is an", "is an early", "an early marker", "early marker of", "marker of mesodermal", "of mesodermal differentiation", "mesodermal differentiation and", "differentiation and is", "and is often", "is often used", "often used in", "used in studies", "in studies of", "studies of embryonic", "of embryonic stem", "embryonic stem cells.", "stem cells. in", "cells. in hescs", "in hescs tbxt", "hescs tbxt is", "tbxt is expressed", "expressed in both", "in both mesodermal", "both mesodermal and", "mesodermal and endodermal", "and endodermal progenitors", "progenitors it", "it regulates different", "regulates different sets", "different sets of", "sets of target", "of target genes", "target genes depending", "genes depending on", "depending on the", "on the signaling", "the signaling environment", "environment faial", "faial et al.", "et al. 2015", "al. 2015 .
              expression", "2015 .
              expression of", ".
              expression of eomes", "of eomes is", "eomes is activated", "activated by nodal", "by nodal via", "nodal via smad2", "via smad2 and", "smad2 and smad3", "and smad3 and", "smad3 and is", "and is observed", "is observed in", "observed in the", "the posterior epiblast", "posterior epiblast prior", "epiblast prior to", "prior to formation", "to formation of", "primitive streak and", "streak and in", "and in mesoderm", "endoderm progenitors during", "progenitors during the", "during the first", "the first day", "first day of", "day of gastrulation.", "of gastrulation. eomes", "gastrulation. eomes in", "eomes in combination", "in combination with", "combination with smad2", "with smad2 3", "smad2 3 is", "3 is crucial", "is crucial for", "crucial for the", "for the activation", "the activation of", "activation of definitive", "of definitive endoderm", "definitive endoderm genes", "genes teo", "teo et al.", "et al. 2011", "al. 2011 .", "2011 . tbxt", ". tbxt and", "tbxt and eomes", "and eomes generally", "eomes generally activate", "generally activate expression", "activate expression of", "expression of mesoderm", "of mesoderm genes", "mesoderm genes and", "genes and repress", "and repress expression", "repress expression of", "expression of genes", "of genes associated", "genes associated with", "associated with pluripotency", "with pluripotency such", "pluripotency such as", "such as sox2", "as sox2 and", "sox2 and nanog.
              some", "and nanog.
              some transcription", "nanog.
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              mixl1", "head development.
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              developing", "2019 ..
              developing mesoderm", "..
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              at", "al. 2021 .
              at the", "2021 .
              at the beginning", ".
              at the beginning of", "the beginning of gastrulation", "beginning of gastrulation in", "of gastrulation in the", "gastrulation in the mouse", "the mouse the", "mouse the primitive", "the primitive streak forms", "primitive streak forms in", "streak forms in a", "forms in a region", "in a region of", "a region of bmp", "of bmp wnt", "fgf and nodal", "and nodal signaling. in", "nodal signaling. in the", "signaling. in the mouse", "in the mouse embryo", "mouse embryo nodal", "embryo nodal is", "nodal is expressed throughout", "is expressed throughout the", "expressed throughout the epiblast", "throughout the epiblast before", "the epiblast before anterior", "epiblast before anterior posterior", "before anterior posterior axis", "anterior posterior axis induction", "posterior axis induction and", "axis induction and is", "induction and is required", "and is required for", "is required for pluripotency", "for pluripotency reviewed", "pluripotency reviewed in", "reviewed in robertson 2014", "in robertson 2014 .", "robertson 2014 . nodal", "2014 . nodal signaling", ". nodal signaling is", "nodal signaling is restricted", "signaling is restricted to", "is restricted to the", "restricted to the posterior", "to the posterior side", "the posterior side of", "posterior side of the", "side of the embryo", "of the embryo by", "the embryo by the", "embryo by the secretion", "by the secretion of", "the secretion of nodal", "secretion of nodal and", "of nodal and wnt", "nodal and wnt antagonists", "wnt antagonists cer1", "lefty1 from the", "from the anterior visceral", "the anterior visceral endoderm", "visceral endoderm ave", "ave reviewed", "reviewed in stower and", "in stower and srinivas", "stower and srinivas 2014", "and srinivas 2014 .", "2014 . in", ". in human", "in human embryonic stem", "human embryonic stem cells", "stem cells hescs", "hescs nodal is", "nodal is also crucial", "is also crucial for", "also crucial for maintenance", "crucial for maintenance of", "for maintenance of pluripotency", "of pluripotency james", "pluripotency james et", "james et al. 2005", "al. 2005 vallier", "2005 vallier et", "vallier et al. 2004", "et al. 2004 .", "al. 2004 . in", "2004 . in mouse", ". in mouse embryos", "mouse embryos nodal", "embryos nodal and", "nodal and wnt3 are", "and wnt3 are required", "wnt3 are required for", "are required for formation", "required for formation of", "for formation of the", "formation of the primitive", "of the primitive streak", "primitive streak conlon", "streak conlon et", "conlon et al. 1994", "al. 1994 brennan", "1994 brennan et", "brennan et al. 2001", "al. 2001 liu", "2001 liu et", "liu et al. 1999", "al. 1999 and", "1999 and nodal", "and nodal expression subsequently", "nodal expression subsequently becomes", "expression subsequently becomes restricted", "subsequently becomes restricted to", "becomes restricted to the", "restricted to the node", "to the node at", "the node at the", "node at the anterior", "at the anterior end", "the anterior end of", "anterior end of the", "end of the primitive", "primitive streak zhou", "streak zhou et", "zhou et al. 1993", "et al. 1993 .", "al. 1993 . pro", "1993 . pro nodal", ". pro nodal secreted", "pro nodal secreted by", "nodal secreted by the", "secreted by the epiblast", "by the epiblast in", "the epiblast in response", "epiblast in response to", "in response to bmp4", "response to bmp4 signalling", "to bmp4 signalling from", "bmp4 signalling from the", "signalling from the extraembryonic", "from the extraembryonic ectoderm", "the extraembryonic ectoderm is", "extraembryonic ectoderm is converted", "ectoderm is converted to", "is converted to mature", "converted to mature nodal", "to mature nodal by", "mature nodal by furin", "by furin pcsk3", "pcsk3 secreted from", "secreted from the extraembryonic", "from the extraembryonic ectoderm.", "the extraembryonic ectoderm. nodal", "extraembryonic ectoderm. nodal maintains", "ectoderm. nodal maintains bmp4", "nodal maintains bmp4 expression", "maintains bmp4 expression in", "bmp4 expression in the", "expression in the extraembryonic", "in the extraembryonic ectoderm", "the extraembryonic ectoderm which", "extraembryonic ectoderm which then", "ectoderm which then activates", "which then activates wnt3", "then activates wnt3 in", "activates wnt3 in the", "wnt3 in the posterior", "in the posterior epiblast.", "the posterior epiblast. wnt", "posterior epiblast. wnt signaling", "wnt signaling in", "signaling in turn", "in turn amplifies", "turn amplifies nodal", "nodal expression brennan", "expression brennan et", "et al. 2001 .", "al. 2001 . the", "2001 . the order", ". the order of", "the order of events", "order of events in", "of events in this", "events in this signaling", "in this signaling cascade", "this signaling cascade may", "signaling cascade may be", "cascade may be different", "may be different in", "be different in human", "different in human embryos", "in human embryos due", "human embryos due to", "embryos due to differences", "due to differences in", "to differences in early", "differences in early embryo", "in early embryo architecture.
              nodal", "embryo architecture.
              nodal bmp", "bmp and wnt", "and wnt show similar", "wnt show similar effects", "show similar effects on", "similar effects on human", "effects on human 2d", "on human 2d gastruloids", "2d gastruloids martyn", "gastruloids martyn et", "martyn et al. 2019", "et al. 2019 .", "al. 2019 . mesoderm", "2019 . mesoderm and", ". mesoderm and definitive", "mesoderm and definitive endoderm", "and definitive endoderm progenitors", "definitive endoderm progenitors appear", "endoderm progenitors appear to", "progenitors appear to be", "appear to be already", "to be already separate", "be already separate and", "already separate and distinct", "separate and distinct in", "and distinct in the", "distinct in the primitive", "in the primitive streak", "primitive streak therefore", "streak therefore bipotential", "therefore bipotential mesendoderm progenitors", "bipotential mesendoderm progenitors may", "mesendoderm progenitors may be", "progenitors may be transitory", "may be transitory if", "be transitory if they", "transitory if they exist", "they exist probst", "exist probst et", "probst et al. 2021", "et al. 2021 .", "al. 2021 . this", "2021 . this is", ". this is an", "this is an area", "is an area of", "an area of ongoing", "area of ongoing research.
              mesoderm", "of ongoing research.
              mesoderm is", "ongoing research.
              mesoderm is formed", "research.
              mesoderm is formed by", "is formed by an", "formed by an epithelial", "by an epithelial mesenchymal", "an epithelial mesenchymal transition", "epithelial mesenchymal transition that", "mesenchymal transition that produces", "transition that produces an", "that produces an ingression", "produces an ingression of", "an ingression of cells", "ingression of cells through", "of cells through the", "cells through the primitive", "through the primitive streak.", "the primitive streak. endoderm", "primitive streak. endoderm does", "streak. endoderm does not", "endoderm does not show", "does not show a", "not show a complete", "show a complete epithelial", "a complete epithelial mesenchymal", "complete epithelial mesenchymal transition", "epithelial mesenchymal transition and", "mesenchymal transition and instead", "transition and instead forms", "and instead forms by", "instead forms by cell", "forms by cell plasticity", "cell plasticity a", "plasticity a partial", "a partial epithelial mesenchymal", "partial epithelial mesenchymal transition", "epithelial mesenchymal transition in", "mesenchymal transition in which", "transition in which both", "in which both e", "which both e cadherin", "both e cadherin and", "e cadherin and n", "cadherin and n cadherin", "and n cadherin are", "n cadherin are expressed", "expressed inferred", "inferred from mouse embryos", "from mouse embryos in", "mouse embryos in scheibner", "embryos in scheibner et", "in scheibner et al.", "scheibner et al. 2021", "al. 2021 . however", ". however in", "however in mouse", "in mouse embryos endoderm", "mouse embryos endoderm progenitors", "embryos endoderm progenitors still", "endoderm progenitors still ingress", "progenitors still ingress through", "still ingress through the", "ingress through the anterior", "through the anterior region", "the anterior region of", "anterior region of the", "region of the primitive", "primitive streak migrate", "streak migrate with", "migrate with mesoderm cells", "mesoderm cells and", "cells and eventually", "and eventually integrate into", "eventually integrate into the", "integrate into the visceral", "into the visceral endoderm", "the visceral endoderm layer", "visceral endoderm layer to", "endoderm layer to give", "layer to give rise", "to give rise to", "give rise to the", "rise to the definitive", "to the definitive endoderm", "definitive endoderm viotti", "endoderm viotti et", "viotti et al. 2014", "et al. 2014 .
              specific", "al. 2014 .
              specific types", "2014 .
              specific types of", ".
              specific types of mesoderm", "types of mesoderm are", "of mesoderm are formed", "mesoderm are formed sequentially", "are formed sequentially according", "formed sequentially according to", "sequentially according to the", "according to the time", "to the time and", "the time and position", "time and position of", "and position of ingression", "position of ingression of", "of ingression of cells", "the primitive streak. this", "primitive streak. this patterning", "streak. this patterning is", "this patterning is caused", "patterning is caused by", "is caused by gradients", "caused by gradients of", "by gradients of nodal", "of nodal wnt", "wnt and bmp", "and bmp signaling that", "bmp signaling that activate", "signaling that activate transcriptional", "that activate transcriptional programs", "activate transcriptional programs in", "transcriptional programs in the", "programs in the mesoderm", "in the mesoderm progenitors.
              t", "the mesoderm progenitors.
              t box", "mesoderm progenitors.
              t box transcription", "progenitors.
              t box transcription factor", "box transcription factor t", "factor t tbxt", "brachyury and eomesodermin", "and eomesodermin eomes", "eomes are two", "are two of the", "two of the first", "of the first transcription", "the first transcription factors", "first transcription factors expressed", "transcription factors expressed in", "factors expressed in mesoderm", "expressed in mesoderm and", "in mesoderm and endoderm", "mesoderm and endoderm progenitors", "and endoderm progenitors in", "endoderm progenitors in the", "progenitors in the primitive", "primitive streak reviewed", "streak reviewed in", "reviewed in probst and", "in probst and arnold", "probst and arnold 2016", "and arnold 2016 .", "arnold 2016 . the", "2016 . the two", ". the two factors", "the two factors combined", "two factors combined are", "factors combined are required", "combined are required for", "for formation of all", "formation of all mesoderm", "of all mesoderm and", "all mesoderm and endoderm", "and endoderm arnold", "endoderm arnold et", "arnold et al. 2008", "al. 2008 tosic", "2008 tosic et", "tosic et al. 2019", "et al. 2019 .
              tbxt", "al. 2019 .
              tbxt is", "2019 .
              tbxt is activated", ".
              tbxt is activated by", "is activated by wnt", "activated by wnt signaling", "wnt signaling via", "signaling via beta", "via beta catenin acting", "beta catenin acting with", "catenin acting with lef1", "acting with lef1 or", "with lef1 or tcf1", "or tcf1 and", "tcf1 and bmp4", "and bmp4 and is", "bmp4 and is expressed", "and is expressed in", "is expressed in mesodermal", "expressed in mesodermal and", "in mesodermal and axial", "mesodermal and axial mesodermal", "and axial mesodermal progenitors", "axial mesodermal progenitors and", "mesodermal progenitors and in", "progenitors and in the", "and in the primitive", "the primitive streak during", "primitive streak during gastrulation", "during gastrulation later", "gastrulation later becoming", "later becoming localized to", "becoming localized to the", "localized to the notochord", "to the notochord and", "the notochord and tailbud.", "notochord and tailbud. tbxt", "and tailbud. tbxt is", "tailbud. tbxt is an", "tbxt is an early", "is an early marker", "an early marker of", "early marker of mesodermal", "marker of mesodermal differentiation", "of mesodermal differentiation and", "mesodermal differentiation and is", "differentiation and is often", "and is often used", "is often used in", "often used in studies", "used in studies of", "in studies of embryonic", "studies of embryonic stem", "of embryonic stem cells.", "embryonic stem cells. in", "stem cells. in hescs", "cells. in hescs tbxt", "in hescs tbxt is", "hescs tbxt is expressed", "tbxt is expressed in", "is expressed in both", "expressed in both mesodermal", "in both mesodermal and", "both mesodermal and endodermal", "mesodermal and endodermal progenitors", "endodermal progenitors it", "progenitors it regulates", "it regulates different sets", "regulates different sets of", "different sets of target", "sets of target genes", "of target genes depending", "target genes depending on", "genes depending on the", "depending on the signaling", "on the signaling environment", "signaling environment faial", "environment faial et", "faial et al. 2015", "et al. 2015 .
              expression", "al. 2015 .
              expression of", "2015 .
              expression of eomes", ".
              expression of eomes is", "of eomes is activated", "eomes is activated by", "is activated by nodal", "activated by nodal via", "by nodal via smad2", "nodal via smad2 and", "via smad2 and smad3", "smad2 and smad3 and", "and smad3 and is", "smad3 and is observed", "and is observed in", "is observed in the", "observed in the posterior", "in the posterior epiblast", "the posterior epiblast prior", "posterior epiblast prior to", "epiblast prior to formation", "prior to formation of", "to formation of the", "the primitive streak and", "primitive streak and in", "streak and in mesoderm", "and in mesoderm and", "and endoderm progenitors during", "endoderm progenitors during the", "progenitors during the first", "during the first day", "the first day of", "first day of gastrulation.", "day of gastrulation. eomes", "of gastrulation. eomes in", "gastrulation. eomes in combination", "eomes in combination with", "in combination with smad2", "combination with smad2 3", "with smad2 3 is", "smad2 3 is crucial", "3 is crucial for", "is crucial for the", "crucial for the activation", "for the activation of", "the activation of definitive", "activation of definitive endoderm", "of definitive endoderm genes", "endoderm genes teo", "genes teo et", "teo et al. 2011", "et al. 2011 .", "al. 2011 . tbxt", "2011 . tbxt and", ". tbxt and eomes", "tbxt and eomes generally", "and eomes generally activate", "eomes generally activate expression", "generally activate expression of", "activate expression of mesoderm", "expression of mesoderm genes", "of mesoderm genes and", "mesoderm genes and repress", "genes and repress expression", "and repress expression of", "repress expression of genes", "expression of genes associated", "of genes associated with", "genes associated with pluripotency", "associated with pluripotency such", "with pluripotency such as", "pluripotency such as sox2", "such as sox2 and", "as sox2 and nanog.
              some", "sox2 and nanog.
              some transcription", "and nanog.
              some transcription factors", "nanog.
              some transcription factors are", "transcription factors are particularly", "factors are particularly important", "are particularly important for", "particularly important for regulating", "important for regulating gastrulation", "for regulating gastrulation and", "regulating gastrulation and are", "gastrulation and are also", "and are also used", "are also used as", "also used as markers", "used as markers for", "as markers for particular", "markers for particular stages", "for particular stages and", "particular stages and morphological", "stages and morphological features.", "and morphological features. for", "morphological features. for example", "for example goosecoid", "gsc expression marks", "expression marks the onset", "marks the onset of", "the onset of gastrulation", "of gastrulation is", "gastrulation is first", "is first observed in", "first observed in the", "observed in the primitive", "streak and becomes", "and becomes localized to", "becomes localized to the", "localized to the anterior", "to the anterior end", "primitive streak and then", "streak and then the", "and then the axial", "then the axial mesoderm", "axial mesoderm blum", "mesoderm blum et", "blum et al. 1992", "et al. 1992 .", "al. 1992 . smad2", "1992 . smad2 and", ". smad2 and smad3", "smad2 and smad3 activated", "and smad3 activated by", "smad3 activated by nodal", "activated by nodal are", "by nodal are recruited", "nodal are recruited to", "are recruited to the", "recruited to the gsc", "to the gsc promoter", "the gsc promoter by", "gsc promoter by foxh1", "by foxh1 which", "foxh1 which is", "which is already located", "is already located at", "already located at the", "located at the promoter.", "at the promoter. mixl1", "the promoter. mixl1 also", "promoter. mixl1 also binds", "mixl1 also binds the", "also binds the gsc", "binds the gsc promoter", "the gsc promoter and", "gsc promoter and activates", "promoter and activates expression.", "and activates expression. in", "activates expression. in mice", "in mice gsc", "mice gsc is", "gsc is a regulator", "is a regulator of", "a regulator of head", "regulator of head development.
              mixl1", "of head development.
              mixl1 is", "head development.
              mixl1 is required", "development.
              mixl1 is required for", "is required for formation", "for formation of both", "formation of both mesoderm", "of both mesoderm and", "both mesoderm and definitive", "definitive endoderm hart", "endoderm hart et", "hart et al. 2002", "al. 2002 and", "2002 and is", "and is expressed early", "is expressed early throughout", "expressed early throughout the", "early throughout the primitive", "throughout the primitive streak", "streak and in nascent", "and in nascent mesoderm", "in nascent mesoderm cells", "nascent mesoderm cells exiting", "mesoderm cells exiting the", "cells exiting the streak.", "exiting the streak. expression", "the streak. expression of", "streak. expression of mixl1", "expression of mixl1 is", "of mixl1 is mediated", "mixl1 is mediated downstream", "is mediated downstream by", "mediated downstream by nodal", "downstream by nodal through", "by nodal through smad2", "nodal through smad2 and", "through smad2 and smad3", "smad2 and smad3 binding", "and smad3 binding to", "smad3 binding to the", "binding to the promoter", "to the promoter of", "the promoter of mixl1.", "promoter of mixl1. eomes", "of mixl1. eomes also", "mixl1. eomes also plays", "eomes also plays a", "also plays a direct", "plays a direct role", "a direct role in", "direct role in activating", "role in activating mixl1", "in activating mixl1 and", "activating mixl1 and gsc", "mixl1 and gsc expression", "and gsc expression in", "gsc expression in hescs", "in hescs teo", "hescs teo et", "al. 2011 and", "2011 and in", "and in mouse embryos", "mouse embryos tosic", "embryos tosic et", "et al. 2019 ..
              developing", "al. 2019 ..
              developing mesoderm", "2019 ..
              developing mesoderm becomes", "..
              developing mesoderm becomes specified", "mesoderm becomes specified by", "becomes specified by expression", "specified by expression of", "by expression of transcription", "expression of transcription factors", "of transcription factors such", "transcription factors such as", "factors such as mesp1", "as mesp1 a", "mesp1 a marker", "a marker of cardiac", "marker of cardiac progenitors.", "cardiac progenitors. see", "progenitors. see the", "see the reactome pathway", "the reactome pathway \\cardiogenesis\\.", "to ethical considerations most", "ethical considerations most research", "considerations most research on", "most research on mammalian gastrulation", "research on mammalian gastrulation has", "on mammalian gastrulation has been", "mammalian gastrulation has been performed", "gastrulation has been performed on", "has been performed on mouse", "been performed on mouse embryos.", "performed on mouse embryos. therefore", "on mouse embryos. therefore most", "mouse embryos. therefore most of", "embryos. therefore most of the", "therefore most of the reactions", "most of the reactions described", "of the reactions described in", "the reactions described in this", "reactions described in this section", "described in this section are", "in this section are the", "this section are the results", "section are the results of", "are the results of research", "the results of research in", "results of research in mouse", "of research in mouse embryos.", "research in mouse embryos. significant", "in mouse embryos. significant research", "mouse embryos. significant research has", "embryos. significant research has also", "significant research has also been", "research has also been performed", "has also been performed on", "also been performed on non", "been performed on non human", "performed on non human primates", "on non human primates such", "non human primates such as", "human primates such as cynomolgus", "primates such as cynomolgus monkeys", "as cynomolgus monkeys macaca", "cynomolgus monkeys macaca fascicularis", "macaca fascicularis nakamura", "fascicularis nakamura et", "et al. 2016 sasaki", "al. 2016 sasaki et", "2016 sasaki et al.", "sasaki et al. 2016 .", "et al. 2016 . more", "al. 2016 . more recently", ". more recently human", "more recently human gastrula", "recently human gastrula like", "human gastrula like cell assemblages", "like cell assemblages \\gastruloids\\", "assemblages \\gastruloids\\ generated", "\\gastruloids\\ generated from pluripotent", "generated from pluripotent stem cells", "from pluripotent stem cells have", "pluripotent stem cells have been", "stem cells have been developed", "have been developed moris", "been developed moris et", "developed moris et al.", "et al. 2020 and", "al. 2020 and are", "2020 and are now", "and are now being compared", "are now being compared with", "now being compared with mouse", "being compared with mouse embryos", "with mouse embryos reviewed", "mouse embryos reviewed in", "embryos reviewed in rossant", "reviewed in rossant and tam", "in rossant and tam 2021", "and tam 2021 ghimire", "tam 2021 ghimire et", "2021 ghimire et al.", "ghimire et al. 2021 .
              at", "et al. 2021 .
              at the", "al. 2021 .
              at the beginning", "2021 .
              at the beginning of", ".
              at the beginning of gastrulation", "the beginning of gastrulation in", "beginning of gastrulation in the", "of gastrulation in the mouse", "in the mouse the", "the mouse the primitive", "mouse the primitive streak", "the primitive streak forms in", "primitive streak forms in a", "streak forms in a region", "forms in a region of", "in a region of bmp", "region of bmp wnt", "bmp wnt fgf", "wnt fgf and", "fgf and nodal signaling.", "and nodal signaling. in the", "nodal signaling. in the mouse", "signaling. in the mouse embryo", "the mouse embryo nodal", "mouse embryo nodal is", "embryo nodal is expressed", "nodal is expressed throughout the", "is expressed throughout the epiblast", "expressed throughout the epiblast before", "throughout the epiblast before anterior", "the epiblast before anterior posterior", "epiblast before anterior posterior axis", "before anterior posterior axis induction", "anterior posterior axis induction and", "posterior axis induction and is", "axis induction and is required", "induction and is required for", "and is required for pluripotency", "required for pluripotency reviewed", "for pluripotency reviewed in", "pluripotency reviewed in robertson", "reviewed in robertson 2014 .", "in robertson 2014 . nodal", "robertson 2014 . nodal signaling", "2014 . nodal signaling is", ". nodal signaling is restricted", "nodal signaling is restricted to", "signaling is restricted to the", "is restricted to the posterior", "restricted to the posterior side", "to the posterior side of", "the posterior side of the", "posterior side of the embryo", "side of the embryo by", "of the embryo by the", "the embryo by the secretion", "embryo by the secretion of", "by the secretion of nodal", "the secretion of nodal and", "secretion of nodal and wnt", "of nodal and wnt antagonists", "and wnt antagonists cer1", "antagonists cer1 lefty1", "cer1 lefty1 from", "lefty1 from the anterior", "from the anterior visceral endoderm", "anterior visceral endoderm ave", "ave reviewed in", "reviewed in stower and srinivas", "in stower and srinivas 2014", "stower and srinivas 2014 .", "srinivas 2014 . in", "2014 . in human", ". in human embryonic", "in human embryonic stem cells", "embryonic stem cells hescs", "cells hescs nodal", "hescs nodal is also", "nodal is also crucial for", "is also crucial for maintenance", "also crucial for maintenance of", "crucial for maintenance of pluripotency", "maintenance of pluripotency james", "of pluripotency james et", "pluripotency james et al.", "et al. 2005 vallier", "al. 2005 vallier et", "2005 vallier et al.", "vallier et al. 2004 .", "et al. 2004 . in", "al. 2004 . in mouse", "2004 . in mouse embryos", "in mouse embryos nodal", "mouse embryos nodal and", "embryos nodal and wnt3", "nodal and wnt3 are required", "and wnt3 are required for", "wnt3 are required for formation", "are required for formation of", "required for formation of the", "for formation of the primitive", "formation of the primitive streak", "the primitive streak conlon", "primitive streak conlon et", "streak conlon et al.", "et al. 1994 brennan", "al. 1994 brennan et", "1994 brennan et al.", "et al. 2001 liu", "al. 2001 liu et", "2001 liu et al.", "et al. 1999 and", "al. 1999 and nodal", "1999 and nodal expression", "and nodal expression subsequently becomes", "nodal expression subsequently becomes restricted", "expression subsequently becomes restricted to", "subsequently becomes restricted to the", "becomes restricted to the node", "restricted to the node at", "to the node at the", "the node at the anterior", "node at the anterior end", "at the anterior end of", "the anterior end of the", "anterior end of the primitive", "end of the primitive streak", "the primitive streak zhou", "primitive streak zhou et", "streak zhou et al.", "zhou et al. 1993 .", "et al. 1993 . pro", "al. 1993 . pro nodal", "1993 . pro nodal secreted", ". pro nodal secreted by", "pro nodal secreted by the", "nodal secreted by the epiblast", "secreted by the epiblast in", "by the epiblast in response", "the epiblast in response to", "epiblast in response to bmp4", "in response to bmp4 signalling", "response to bmp4 signalling from", "to bmp4 signalling from the", "bmp4 signalling from the extraembryonic", "signalling from the extraembryonic ectoderm", "from the extraembryonic ectoderm is", "the extraembryonic ectoderm is converted", "extraembryonic ectoderm is converted to", "ectoderm is converted to mature", "is converted to mature nodal", "converted to mature nodal by", "to mature nodal by furin", "nodal by furin pcsk3", "furin pcsk3 secreted", "pcsk3 secreted from the", "secreted from the extraembryonic ectoderm.", "from the extraembryonic ectoderm. nodal", "the extraembryonic ectoderm. nodal maintains", "extraembryonic ectoderm. nodal maintains bmp4", "ectoderm. nodal maintains bmp4 expression", "nodal maintains bmp4 expression in", "maintains bmp4 expression in the", "bmp4 expression in the extraembryonic", "expression in the extraembryonic ectoderm", "in the extraembryonic ectoderm which", "the extraembryonic ectoderm which then", "extraembryonic ectoderm which then activates", "ectoderm which then activates wnt3", "which then activates wnt3 in", "then activates wnt3 in the", "activates wnt3 in the posterior", "wnt3 in the posterior epiblast.", "in the posterior epiblast. wnt", "the posterior epiblast. wnt signaling", "epiblast. wnt signaling in", "wnt signaling in turn", "in turn amplifies nodal", "turn amplifies nodal expression", "amplifies nodal expression brennan", "nodal expression brennan et", "expression brennan et al.", "brennan et al. 2001 .", "et al. 2001 . the", "al. 2001 . the order", "2001 . the order of", ". the order of events", "the order of events in", "order of events in this", "of events in this signaling", "events in this signaling cascade", "in this signaling cascade may", "this signaling cascade may be", "signaling cascade may be different", "cascade may be different in", "may be different in human", "be different in human embryos", "different in human embryos due", "in human embryos due to", "human embryos due to differences", "embryos due to differences in", "due to differences in early", "to differences in early embryo", "differences in early embryo architecture.
              nodal", "early embryo architecture.
              nodal bmp", "architecture.
              nodal bmp and", "bmp and wnt show", "and wnt show similar effects", "wnt show similar effects on", "show similar effects on human", "similar effects on human 2d", "effects on human 2d gastruloids", "human 2d gastruloids martyn", "2d gastruloids martyn et", "gastruloids martyn et al.", "martyn et al. 2019 .", "et al. 2019 . mesoderm", "al. 2019 . mesoderm and", "2019 . mesoderm and definitive", ". mesoderm and definitive endoderm", "mesoderm and definitive endoderm progenitors", "and definitive endoderm progenitors appear", "definitive endoderm progenitors appear to", "endoderm progenitors appear to be", "progenitors appear to be already", "appear to be already separate", "to be already separate and", "be already separate and distinct", "already separate and distinct in", "separate and distinct in the", "and distinct in the primitive", "distinct in the primitive streak", "the primitive streak therefore", "primitive streak therefore bipotential", "streak therefore bipotential mesendoderm", "therefore bipotential mesendoderm progenitors may", "bipotential mesendoderm progenitors may be", "mesendoderm progenitors may be transitory", "progenitors may be transitory if", "may be transitory if they", "be transitory if they exist", "if they exist probst", "they exist probst et", "exist probst et al.", "probst et al. 2021 .", "et al. 2021 . this", "al. 2021 . this is", "2021 . this is an", ". this is an area", "this is an area of", "is an area of ongoing", "an area of ongoing research.
              mesoderm", "area of ongoing research.
              mesoderm is", "of ongoing research.
              mesoderm is formed", "ongoing research.
              mesoderm is formed by", "research.
              mesoderm is formed by an", "is formed by an epithelial", "formed by an epithelial mesenchymal", "by an epithelial mesenchymal transition", "an epithelial mesenchymal transition that", "epithelial mesenchymal transition that produces", "mesenchymal transition that produces an", "transition that produces an ingression", "that produces an ingression of", "produces an ingression of cells", "an ingression of cells through", "ingression of cells through the", "of cells through the primitive", "cells through the primitive streak.", "through the primitive streak. endoderm", "the primitive streak. endoderm does", "primitive streak. endoderm does not", "streak. endoderm does not show", "endoderm does not show a", "does not show a complete", "not show a complete epithelial", "show a complete epithelial mesenchymal", "a complete epithelial mesenchymal transition", "complete epithelial mesenchymal transition and", "epithelial mesenchymal transition and instead", "mesenchymal transition and instead forms", "transition and instead forms by", "and instead forms by cell", "instead forms by cell plasticity", "by cell plasticity a", "cell plasticity a partial", "plasticity a partial epithelial", "a partial epithelial mesenchymal transition", "partial epithelial mesenchymal transition in", "epithelial mesenchymal transition in which", "mesenchymal transition in which both", "transition in which both e", "in which both e cadherin", "which both e cadherin and", "both e cadherin and n", "e cadherin and n cadherin", "cadherin and n cadherin are", "and n cadherin are expressed", "are expressed inferred", "expressed inferred from", "inferred from mouse embryos in", "from mouse embryos in scheibner", "mouse embryos in scheibner et", "embryos in scheibner et al.", "in scheibner et al. 2021", "scheibner et al. 2021 .", "et al. 2021 . however", "2021 . however in", ". however in mouse", "however in mouse embryos", "in mouse embryos endoderm progenitors", "mouse embryos endoderm progenitors still", "embryos endoderm progenitors still ingress", "endoderm progenitors still ingress through", "progenitors still ingress through the", "still ingress through the anterior", "ingress through the anterior region", "through the anterior region of", "the anterior region of the", "anterior region of the primitive", "region of the primitive streak", "the primitive streak migrate", "primitive streak migrate with", "streak migrate with mesoderm", "with mesoderm cells and", "mesoderm cells and eventually", "cells and eventually integrate", "and eventually integrate into the", "eventually integrate into the visceral", "integrate into the visceral endoderm", "into the visceral endoderm layer", "the visceral endoderm layer to", "visceral endoderm layer to give", "endoderm layer to give rise", "layer to give rise to", "to give rise to the", "give rise to the definitive", "rise to the definitive endoderm", "the definitive endoderm viotti", "definitive endoderm viotti et", "endoderm viotti et al.", "viotti et al. 2014 .
              specific", "et al. 2014 .
              specific types", "al. 2014 .
              specific types of", "2014 .
              specific types of mesoderm", ".
              specific types of mesoderm are", "types of mesoderm are formed", "of mesoderm are formed sequentially", "mesoderm are formed sequentially according", "are formed sequentially according to", "formed sequentially according to the", "sequentially according to the time", "according to the time and", "to the time and position", "the time and position of", "time and position of ingression", "and position of ingression of", "position of ingression of cells", "of ingression of cells through", "through the primitive streak. this", "the primitive streak. this patterning", "primitive streak. this patterning is", "streak. this patterning is caused", "this patterning is caused by", "patterning is caused by gradients", "is caused by gradients of", "caused by gradients of nodal", "gradients of nodal wnt", "nodal wnt and", "wnt and bmp signaling", "and bmp signaling that activate", "bmp signaling that activate transcriptional", "signaling that activate transcriptional programs", "that activate transcriptional programs in", "activate transcriptional programs in the", "transcriptional programs in the mesoderm", "programs in the mesoderm progenitors.
              t", "in the mesoderm progenitors.
              t box", "the mesoderm progenitors.
              t box transcription", "mesoderm progenitors.
              t box transcription factor", "progenitors.
              t box transcription factor t", "transcription factor t tbxt", "t tbxt t", "tbxt t brachyury", "t brachyury and", "eomesodermin eomes are", "eomes are two of", "are two of the first", "two of the first transcription", "of the first transcription factors", "the first transcription factors expressed", "first transcription factors expressed in", "transcription factors expressed in mesoderm", "factors expressed in mesoderm and", "expressed in mesoderm and endoderm", "in mesoderm and endoderm progenitors", "mesoderm and endoderm progenitors in", "and endoderm progenitors in the", "endoderm progenitors in the primitive", "progenitors in the primitive streak", "the primitive streak reviewed", "primitive streak reviewed in", "streak reviewed in probst", "reviewed in probst and arnold", "in probst and arnold 2016", "probst and arnold 2016 .", "and arnold 2016 . the", "arnold 2016 . the two", "2016 . the two factors", ". the two factors combined", "the two factors combined are", "two factors combined are required", "factors combined are required for", "combined are required for formation", "required for formation of all", "for formation of all mesoderm", "formation of all mesoderm and", "of all mesoderm and endoderm", "mesoderm and endoderm arnold", "and endoderm arnold et", "endoderm arnold et al.", "et al. 2008 tosic", "al. 2008 tosic et", "2008 tosic et al.", "tosic et al. 2019 .
              tbxt", "et al. 2019 .
              tbxt is", "al. 2019 .
              tbxt is activated", "2019 .
              tbxt is activated by", ".
              tbxt is activated by wnt", "is activated by wnt signaling", "by wnt signaling via", "wnt signaling via beta", "signaling via beta catenin", "via beta catenin acting with", "beta catenin acting with lef1", "catenin acting with lef1 or", "acting with lef1 or tcf1", "lef1 or tcf1 and", "or tcf1 and bmp4", "tcf1 and bmp4 and", "and bmp4 and is expressed", "bmp4 and is expressed in", "and is expressed in mesodermal", "is expressed in mesodermal and", "expressed in mesodermal and axial", "in mesodermal and axial mesodermal", "mesodermal and axial mesodermal progenitors", "and axial mesodermal progenitors and", "axial mesodermal progenitors and in", "mesodermal progenitors and in the", "progenitors and in the primitive", "and in the primitive streak", "in the primitive streak during", "the primitive streak during gastrulation", "streak during gastrulation later", "during gastrulation later becoming", "gastrulation later becoming localized", "later becoming localized to the", "becoming localized to the notochord", "localized to the notochord and", "to the notochord and tailbud.", "the notochord and tailbud. tbxt", "notochord and tailbud. tbxt is", "and tailbud. tbxt is an", "tailbud. tbxt is an early", "tbxt is an early marker", "is an early marker of", "an early marker of mesodermal", "early marker of mesodermal differentiation", "marker of mesodermal differentiation and", "of mesodermal differentiation and is", "mesodermal differentiation and is often", "differentiation and is often used", "and is often used in", "is often used in studies", "often used in studies of", "used in studies of embryonic", "in studies of embryonic stem", "studies of embryonic stem cells.", "of embryonic stem cells. in", "embryonic stem cells. in hescs", "stem cells. in hescs tbxt", "cells. in hescs tbxt is", "in hescs tbxt is expressed", "hescs tbxt is expressed in", "tbxt is expressed in both", "is expressed in both mesodermal", "expressed in both mesodermal and", "in both mesodermal and endodermal", "both mesodermal and endodermal progenitors", "and endodermal progenitors it", "endodermal progenitors it regulates", "progenitors it regulates different", "it regulates different sets of", "regulates different sets of target", "different sets of target genes", "sets of target genes depending", "of target genes depending on", "target genes depending on the", "genes depending on the signaling", "depending on the signaling environment", "the signaling environment faial", "signaling environment faial et", "environment faial et al.", "faial et al. 2015 .
              expression", "et al. 2015 .
              expression of", "al. 2015 .
              expression of eomes", "2015 .
              expression of eomes is", ".
              expression of eomes is activated", "of eomes is activated by", "eomes is activated by nodal", "is activated by nodal via", "activated by nodal via smad2", "by nodal via smad2 and", "nodal via smad2 and smad3", "via smad2 and smad3 and", "smad2 and smad3 and is", "and smad3 and is observed", "smad3 and is observed in", "and is observed in the", "is observed in the posterior", "observed in the posterior epiblast", "in the posterior epiblast prior", "the posterior epiblast prior to", "posterior epiblast prior to formation", "epiblast prior to formation of", "prior to formation of the", "to formation of the primitive", "of the primitive streak and", "the primitive streak and in", "primitive streak and in mesoderm", "streak and in mesoderm and", "and in mesoderm and endoderm", "mesoderm and endoderm progenitors during", "and endoderm progenitors during the", "endoderm progenitors during the first", "progenitors during the first day", "during the first day of", "the first day of gastrulation.", "first day of gastrulation. eomes", "day of gastrulation. eomes in", "of gastrulation. eomes in combination", "gastrulation. eomes in combination with", "eomes in combination with smad2", "in combination with smad2 3", "combination with smad2 3 is", "with smad2 3 is crucial", "smad2 3 is crucial for", "3 is crucial for the", "is crucial for the activation", "crucial for the activation of", "for the activation of definitive", "the activation of definitive endoderm", "activation of definitive endoderm genes", "definitive endoderm genes teo", "endoderm genes teo et", "genes teo et al.", "teo et al. 2011 .", "et al. 2011 . tbxt", "al. 2011 . tbxt and", "2011 . tbxt and eomes", ". tbxt and eomes generally", "tbxt and eomes generally activate", "and eomes generally activate expression", "eomes generally activate expression of", "generally activate expression of mesoderm", "activate expression of mesoderm genes", "expression of mesoderm genes and", "of mesoderm genes and repress", "mesoderm genes and repress expression", "genes and repress expression of", "and repress expression of genes", "repress expression of genes associated", "expression of genes associated with", "of genes associated with pluripotency", "genes associated with pluripotency such", "associated with pluripotency such as", "with pluripotency such as sox2", "pluripotency such as sox2 and", "such as sox2 and nanog.
              some", "as sox2 and nanog.
              some transcription", "sox2 and nanog.
              some transcription factors", "and nanog.
              some transcription factors are", "nanog.
              some transcription factors are particularly", "transcription factors are particularly important", "factors are particularly important for", "are particularly important for regulating", "particularly important for regulating gastrulation", "important for regulating gastrulation and", "for regulating gastrulation and are", "regulating gastrulation and are also", "gastrulation and are also used", "and are also used as", "are also used as markers", "also used as markers for", "used as markers for particular", "as markers for particular stages", "markers for particular stages and", "for particular stages and morphological", "particular stages and morphological features.", "stages and morphological features. for", "and morphological features. for example", "features. for example goosecoid", "example goosecoid gsc", "goosecoid gsc expression", "gsc expression marks the", "expression marks the onset of", "marks the onset of gastrulation", "onset of gastrulation is", "of gastrulation is first", "gastrulation is first observed", "is first observed in the", "first observed in the primitive", "observed in the primitive streak", "primitive streak and becomes", "streak and becomes localized", "and becomes localized to the", "becomes localized to the anterior", "localized to the anterior end", "to the anterior end of", "the primitive streak and then", "primitive streak and then the", "streak and then the axial", "and then the axial mesoderm", "the axial mesoderm blum", "axial mesoderm blum et", "mesoderm blum et al.", "blum et al. 1992 .", "et al. 1992 . smad2", "al. 1992 . smad2 and", "1992 . smad2 and smad3", ". smad2 and smad3 activated", "smad2 and smad3 activated by", "and smad3 activated by nodal", "smad3 activated by nodal are", "activated by nodal are recruited", "by nodal are recruited to", "nodal are recruited to the", "are recruited to the gsc", "recruited to the gsc promoter", "to the gsc promoter by", "the gsc promoter by foxh1", "promoter by foxh1 which", "by foxh1 which is", "foxh1 which is already", "which is already located at", "is already located at the", "already located at the promoter.", "located at the promoter. mixl1", "at the promoter. mixl1 also", "the promoter. mixl1 also binds", "promoter. mixl1 also binds the", "mixl1 also binds the gsc", "also binds the gsc promoter", "binds the gsc promoter and", "the gsc promoter and activates", "gsc promoter and activates expression.", "promoter and activates expression. in", "and activates expression. in mice", "expression. in mice gsc", "in mice gsc is", "mice gsc is a", "gsc is a regulator of", "is a regulator of head", "a regulator of head development.
              mixl1", "regulator of head development.
              mixl1 is", "of head development.
              mixl1 is required", "head development.
              mixl1 is required for", "development.
              mixl1 is required for formation", "is required for formation of", "required for formation of both", "for formation of both mesoderm", "formation of both mesoderm and", "of both mesoderm and definitive", "both mesoderm and definitive endoderm", "and definitive endoderm hart", "definitive endoderm hart et", "endoderm hart et al.", "et al. 2002 and", "al. 2002 and is", "2002 and is expressed", "and is expressed early throughout", "is expressed early throughout the", "expressed early throughout the primitive", "early throughout the primitive streak", "throughout the primitive streak and", "primitive streak and in nascent", "streak and in nascent mesoderm", "and in nascent mesoderm cells", "in nascent mesoderm cells exiting", "nascent mesoderm cells exiting the", "mesoderm cells exiting the streak.", "cells exiting the streak. expression", "exiting the streak. expression of", "the streak. expression of mixl1", "streak. expression of mixl1 is", "expression of mixl1 is mediated", "of mixl1 is mediated downstream", "mixl1 is mediated downstream by", "is mediated downstream by nodal", "mediated downstream by nodal through", "downstream by nodal through smad2", "by nodal through smad2 and", "nodal through smad2 and smad3", "through smad2 and smad3 binding", "smad2 and smad3 binding to", "and smad3 binding to the", "smad3 binding to the promoter", "binding to the promoter of", "to the promoter of mixl1.", "the promoter of mixl1. eomes", "promoter of mixl1. eomes also", "of mixl1. eomes also plays", "mixl1. eomes also plays a", "eomes also plays a direct", "also plays a direct role", "plays a direct role in", "a direct role in activating", "direct role in activating mixl1", "role in activating mixl1 and", "in activating mixl1 and gsc", "activating mixl1 and gsc expression", "mixl1 and gsc expression in", "and gsc expression in hescs", "expression in hescs teo", "in hescs teo et", "hescs teo et al.", "et al. 2011 and", "al. 2011 and in", "2011 and in mouse", "in mouse embryos tosic", "mouse embryos tosic et", "embryos tosic et al.", "tosic et al. 2019 ..
              developing", "et al. 2019 ..
              developing mesoderm", "al. 2019 ..
              developing mesoderm becomes", "2019 ..
              developing mesoderm becomes specified", "..
              developing mesoderm becomes specified by", "mesoderm becomes specified by expression", "becomes specified by expression of", "specified by expression of transcription", "by expression of transcription factors", "expression of transcription factors such", "of transcription factors such as", "transcription factors such as mesp1", "such as mesp1 a", "as mesp1 a marker", "mesp1 a marker of", "a marker of cardiac progenitors.", "of cardiac progenitors. see", "cardiac progenitors. see the", "progenitors. see the reactome", "see the reactome pathway \\cardiogenesis\\." ] }, { "record_id": "GLY_000594_1_1880", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9755511", "r hsa", "hsa 9755511", "r hsa 9755511" ] }, { "record_id": "GLY_000594_1_1880", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "keap1 nfe2l2", "nfe2l2 pathway", "keap1 nfe2l2 pathway", "the keap1:nfe2l2", "keap1 nrf2", "kelch like", "like ech", "ech associated", "associated protein", "protein 1", "1 nuclear", "nuclear factor", "erythroid derived", "derived 2", "like 2", "regulatory pathway", "pathway plays", "plays a", "a central", "central role", "role in", "in protecting", "protecting cells", "cells against", "against multiple", "multiple homeostatic", "homeostatic responses", "responses including", "including adaptation", "adaptation to", "to oxidative", "proteotoxic and", "and xenobiotic", "xenobiotic stresses.", "stresses. the", "the nfe2l2", "nfe2l2 transcriptome", "transcriptome has", "has been", "been implicated", "implicated in", "in protection", "protection against", "against many", "many chronic", "chronic diseases", "diseases including", "including cardiovascular", "neurodgenerative and", "and respiratory", "respiratory diseases", "reviewed in", "in cuadrado", "cuadrado et", "et al", "baird and", "and yamamoto", "2020 .", ". in", "in cancer", "nfe2l2 plays", "a critical", "critical role", "in the", "the metabolic", "metabolic reprogramming", "directing metabolic", "metabolic intermediates", "intermediates into", "into the", "the warburg", "warburg and", "and pentose", "pentose phosphate", "phosphate pathways", "pathways to", "to support", "support proliferative", "proliferative growth", "growth and", "and redox", "redox homeostasis", "in he", "he et", "ge et", "hayes et", "kitamura and", "and hotomashi", "2018

              keap1", "

              keap1 is", "is a", "a redox", "redox sensor", "sensor that", "that together", "together with", "with cul3/rbx1", "cul3/rbx1 forms", "forms part", "part of", "of an", "an e3", "e3 ubiquitin", "ubiquitin ligase", "which tightly", "tightly regulates", "regulates the", "the activity", "activity of", "of the", "the transcription", "transcription factor", "factor nfe2l2", "nfe2l2 by", "by targeting", "targeting it", "it for", "for ubiquitination", "ubiquitination and", "and proteasome", "proteasome dependent", "dependent degradation.", "degradation. oxidative", "oxidative modifications", "modifications or", "or electrophile", "electrophile adduct", "adduct formation", "formation with", "with redox", "redox sensitive", "sensitive cysteines", "cysteines within", "within keap1", "keap1 renders", "renders this", "this protein", "protein unable", "unable to", "to target", "target bound", "bound nfe2l2", "nfe2l2 for", "and allows", "allows newly", "newly translated", "translated nfe2l2", "nfe2l2 to", "to accumulate", "accumulate within", "within the", "the cell", "cell and", "and translocate", "translocate to", "to the", "the nucleus", "nucleus where", "where it", "it can", "can promote", "promote its", "its transcriptional", "transcriptional program", "2020 .
              ", "keap1:nfe2l2 keap1", "nrf2 kelch", "kelch like ech", "like ech associated", "ech associated protein", "associated protein 1", "protein 1 nuclear", "1 nuclear factor", "factor erythroid", "erythroid derived 2", "2 like", "2 regulatory", "regulatory pathway plays", "pathway plays a", "plays a central", "a central role", "central role in", "role in protecting", "in protecting cells", "protecting cells against", "cells against multiple", "against multiple homeostatic", "multiple homeostatic responses", "homeostatic responses including", "responses including adaptation", "including adaptation to", "adaptation to oxidative", "oxidative inflammatory", "inflammatory metabolic", "metabolic proteotoxic", "proteotoxic and xenobiotic", "and xenobiotic stresses.", "xenobiotic stresses. the", "stresses. the nfe2l2", "the nfe2l2 transcriptome", "nfe2l2 transcriptome has", "transcriptome has been", "has been implicated", "been implicated in", "implicated in protection", "in protection against", "protection against many", "against many chronic", "many chronic diseases", "chronic diseases including", "diseases including cardiovascular", "cardiovascular metabolic", "metabolic neurodgenerative", "neurodgenerative and respiratory", "and respiratory diseases", "diseases reviewed", "reviewed in cuadrado", "in cuadrado et", "cuadrado et al", "al 2018", "2018 baird", "baird and yamamoto", "yamamoto 2020", "2020 . in", ". in cancer", "cancer nfe2l2", "nfe2l2 plays a", "plays a critical", "a critical role", "critical role in", "role in the", "in the metabolic", "the metabolic reprogramming", "reprogramming directing", "directing metabolic intermediates", "metabolic intermediates into", "intermediates into the", "into the warburg", "the warburg and", "warburg and pentose", "and pentose phosphate", "pentose phosphate pathways", "phosphate pathways to", "pathways to support", "to support proliferative", "support proliferative growth", "proliferative growth and", "growth and redox", "and redox homeostasis", "homeostasis reviewed", "reviewed in he", "in he et", "he et al", "al 2020", "2020 ge", "ge et al", "2020 hayes", "hayes et al", "2020 kitamura", "kitamura and hotomashi", "hotomashi 2018", "2018

              keap1 is", "

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              keap1", "2018

              keap1 is a", "

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              ", "the keap1:nfe2l2 keap1 nrf2", "keap1 nrf2 kelch like", "nrf2 kelch like ech", "kelch like ech associated protein", "like ech associated protein 1", "ech associated protein 1 nuclear", "associated protein 1 nuclear factor", "1 nuclear factor erythroid", "nuclear factor erythroid derived", "factor erythroid derived 2", "erythroid derived 2 like", "derived 2 like 2", "like 2 regulatory pathway", "2 regulatory pathway plays", "regulatory pathway plays a central", "pathway plays a central role", "plays a central role in", "a central role in protecting", "central role in protecting cells", "role in protecting cells against", "in protecting cells against multiple", "protecting cells against multiple homeostatic", "cells against multiple homeostatic responses", "against multiple homeostatic responses including", "multiple homeostatic responses including adaptation", "homeostatic responses including adaptation to", "responses including adaptation to oxidative", "adaptation to oxidative inflammatory", "oxidative inflammatory metabolic", "inflammatory metabolic proteotoxic", "metabolic proteotoxic and xenobiotic", "proteotoxic and xenobiotic stresses. the", "and xenobiotic stresses. the nfe2l2", "xenobiotic stresses. the nfe2l2 transcriptome", "stresses. the nfe2l2 transcriptome has", "the nfe2l2 transcriptome has been", "nfe2l2 transcriptome has been implicated", "transcriptome has been implicated in", "has been implicated in protection", "been implicated in protection against", "implicated in protection against many", "in protection against many chronic", "protection against many chronic diseases", "against many chronic diseases including", "many chronic diseases including cardiovascular", "diseases including cardiovascular metabolic", "cardiovascular metabolic neurodgenerative", "metabolic neurodgenerative and respiratory", "and respiratory diseases reviewed", "respiratory diseases reviewed in", "diseases reviewed in cuadrado", "reviewed in cuadrado et al", "cuadrado et al 2018", "al 2018 baird", "2018 baird and yamamoto", "baird and yamamoto 2020", "and yamamoto 2020 .", "yamamoto 2020 . in", ". in cancer nfe2l2", "in cancer nfe2l2 plays", "cancer nfe2l2 plays a", "nfe2l2 plays a critical role", "plays a critical role in", "a critical role in the", "critical role in the metabolic", "role in the metabolic reprogramming", "the metabolic reprogramming directing", "metabolic reprogramming directing metabolic", "reprogramming directing metabolic intermediates", "directing metabolic intermediates into the", "metabolic intermediates into the warburg", "intermediates into the warburg and", "into the warburg and pentose", "the warburg and pentose phosphate", "warburg and pentose phosphate pathways", "and pentose phosphate pathways to", "pentose phosphate pathways to support", "phosphate pathways to support proliferative", "pathways to support proliferative growth", "to support proliferative growth and", "support proliferative growth and redox", "proliferative growth and redox homeostasis", "and redox homeostasis reviewed", "redox homeostasis reviewed in", "homeostasis reviewed in he", "reviewed in he et al", "he et al 2020", "al 2020 ge", "2020 ge et al", "ge et al 2020", "al 2020 hayes", "2020 hayes et al", "hayes et al 2020", "al 2020 kitamura", "2020 kitamura and hotomashi", "kitamura and hotomashi 2018", "and hotomashi 2018

              keap1", "hotomashi 2018

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              keap1 is a redox", "

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              " ] }, { "record_id": "GLY_000594_1_1881", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9755779", "r hsa", "hsa 9755779", "r hsa 9755779" ] }, { "record_id": "GLY_000594_1_1881", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 2", "2 targets", "targets host", "host intracellular", "intracellular signalling", "signalling and", "and regulatory", "regulatory pathways", "sars cov 2", "cov 2 targets", "2 targets host", "targets host intracellular", "host intracellular signalling", "intracellular signalling and", "signalling and regulatory", "and regulatory pathways", "sars cov 2 targets", "cov 2 targets host", "2 targets host intracellular", "targets host intracellular signalling", "host intracellular signalling and", "intracellular signalling and regulatory", "signalling and regulatory pathways", "sars cov 2 targets host", "cov 2 targets host intracellular", "2 targets host intracellular signalling", "targets host intracellular signalling and", "host intracellular signalling and regulatory", "intracellular signalling and regulatory pathways", "severe acute", "acute respiratory", "respiratory syndrome", "syndrome coronavirus", "coronavirus type", "type 2", "encodes several", "several proteins", "proteins that", "that modulate", "modulate host", "intracellular signaling", "signaling and", "regulatory pathways.", "pathways. among", "among them", "them are", "are membrane", "membrane m", "nucleocapsid n", "n and", "and 3a", "3a proteins", "that directly", "directly bind", "bind to", "to host", "host targets", "targets associated", "associated with", "with sars\u2011cov\u20112", "sars\u2011cov\u20112 infection", "infection and", "and cytokine", "cytokine production.", "production. this", "this reactome", "reactome module", "module describes", "describes several", "several such", "such binding", "binding events", "events and", "and their", "their consequences.", "consequences. first", "sars\u2011cov\u20112 m", "m binds", "binds to", "to 3\u2011phosphoinositide\u2011dependent", "3\u2011phosphoinositide\u2011dependent protein", "protein kinase", "kinase 1", "to inhibit", "inhibit pkb/akt", "pkb/akt activation", "ren y", "y et", "et al.", "al. 2021", "2021 .", ". second", "sars\u2011cov\u20111 n", "n binds", "to the", "the host", "host 14", "14 3", "3 3", "3 protein", "which regulates", "regulates nucleocytoplasmic", "nucleocytoplasmic shuttling", "shuttling and", "and other", "other functions", "functions of", "of n", "tugaeva kv", "kv et", ". third", "binding of", "of viral", "viral 3a", "3a to", "the regulator", "regulator and", "and scaffolding", "scaffolding protein", "protein caveolin\u20111", "may regulate", "regulate virus", "virus uptake", "uptake as", "as well", "well as", "as the", "the trafficking", "trafficking of", "viral structural", "structural proteins", "inferred from", "from the", "the orthologous", "orthologous protein", "protein in", "in sars", "cov 1", "1 .", "severe acute respiratory", "acute respiratory syndrome", "respiratory syndrome coronavirus", "syndrome coronavirus type", "coronavirus type 2", "2 sars\u2011cov\u20112", "sars\u2011cov\u20112 encodes", "encodes several proteins", "several proteins that", "proteins that modulate", "that modulate host", "modulate host intracellular", "host intracellular signaling", "intracellular signaling and", "signaling and regulatory", "and regulatory pathways.", "regulatory pathways. among", "pathways. among them", "among them are", "them are membrane", "are membrane m", "m nucleocapsid", "nucleocapsid n and", "n and 3a", "and 3a proteins", "3a proteins that", "proteins that directly", "that directly bind", "directly bind to", "bind to host", "to host targets", "host targets associated", "targets associated with", "associated with sars\u2011cov\u20112", "with sars\u2011cov\u20112 infection", "sars\u2011cov\u20112 infection and", "infection and cytokine", "and cytokine production.", "cytokine production. this", "production. this reactome", "this reactome module", "reactome module describes", "module describes several", "describes several such", "several such binding", "such binding events", "binding events and", "events and their", "and their consequences.", "their consequences. first", "first sars\u2011cov\u20112", "sars\u2011cov\u20112 m binds", "m binds to", "binds to 3\u2011phosphoinositide\u2011dependent", "to 3\u2011phosphoinositide\u2011dependent protein", "3\u2011phosphoinositide\u2011dependent protein kinase", "protein kinase 1", "1 pdpk1", "pdpk1 to", "to inhibit pkb/akt", "inhibit pkb/akt activation", "activation ren", "ren y et", "y et al.", "et al. 2021", "al. 2021 .", "2021 . second", "second sars\u2011cov\u20111", "sars\u2011cov\u20111 n binds", "n binds to", "binds to the", "to the host", "the host 14", "host 14 3", "14 3 3", "3 3 protein", "protein which", "which regulates nucleocytoplasmic", "regulates nucleocytoplasmic shuttling", "nucleocytoplasmic shuttling and", "shuttling and other", "and other functions", "other functions of", "functions of n", "n tugaeva", "tugaeva kv et", "kv et al.", "2021 . third", "third binding", "binding of viral", "of viral 3a", "viral 3a to", "3a to the", "to the regulator", "the regulator and", "regulator and scaffolding", "and scaffolding protein", "scaffolding protein caveolin\u20111", "caveolin\u20111 cav1", "cav1 may", "may regulate virus", "regulate virus uptake", "virus uptake as", "uptake as well", "as well as", "well as the", "as the trafficking", "the trafficking of", "trafficking of viral", "of viral structural", "viral structural proteins", "proteins inferred", "inferred from the", "from the orthologous", "the orthologous protein", "orthologous protein in", "protein in sars", "in sars cov", "sars cov 1", "cov 1 .", "severe acute respiratory syndrome", "acute respiratory syndrome coronavirus", "respiratory syndrome coronavirus type", "syndrome coronavirus type 2", "type 2 sars\u2011cov\u20112", "sars\u2011cov\u20112 encodes several", "encodes several proteins that", "several proteins that modulate", "proteins that modulate host", "that modulate host intracellular", "modulate host intracellular signaling", "host intracellular signaling and", "intracellular signaling and regulatory", "signaling and regulatory pathways.", "and regulatory pathways. among", "regulatory pathways. among them", "pathways. among them are", "among them are membrane", "them are membrane m", "membrane m nucleocapsid", "m nucleocapsid n", "nucleocapsid n and 3a", "n and 3a proteins", "and 3a proteins that", "3a proteins that directly", "proteins that directly bind", "that directly bind to", "directly bind to host", "bind to host targets", "to host targets associated", "host targets associated with", "targets associated with sars\u2011cov\u20112", "associated with sars\u2011cov\u20112 infection", "with sars\u2011cov\u20112 infection and", "sars\u2011cov\u20112 infection and cytokine", "infection and cytokine production.", "and cytokine production. this", "cytokine production. this reactome", "production. this reactome module", "this reactome module describes", "reactome module describes several", "module describes several such", "describes several such binding", "several such binding events", "such binding events and", "binding events and their", "events and their consequences.", "and their consequences. first", "consequences. first sars\u2011cov\u20112", "first sars\u2011cov\u20112 m", "sars\u2011cov\u20112 m binds to", "m binds to 3\u2011phosphoinositide\u2011dependent", "binds to 3\u2011phosphoinositide\u2011dependent protein", "to 3\u2011phosphoinositide\u2011dependent protein kinase", "3\u2011phosphoinositide\u2011dependent protein kinase 1", "kinase 1 pdpk1", "pdpk1 to inhibit", "to inhibit pkb/akt activation", "pkb/akt activation ren", "activation ren y", "ren y et al.", "y et al. 2021", "et al. 2021 .", "al. 2021 . second", ". second sars\u2011cov\u20111", "second sars\u2011cov\u20111 n", "sars\u2011cov\u20111 n binds to", "n binds to the", "binds to the host", "to the host 14", "the host 14 3", "host 14 3 3", "14 3 3 protein", "3 protein which", "protein which regulates", "which regulates nucleocytoplasmic shuttling", "regulates nucleocytoplasmic shuttling and", "nucleocytoplasmic shuttling and other", "shuttling and other functions", "and other functions of", "other functions of n", "of n tugaeva", "n tugaeva kv", "tugaeva kv et al.", "kv et al. 2021", "al. 2021 . third", ". third binding", "third binding of", "binding of viral 3a", "of viral 3a to", "viral 3a to the", "3a to the regulator", "to the regulator and", "the regulator and scaffolding", "regulator and scaffolding protein", "and scaffolding protein caveolin\u20111", "protein caveolin\u20111 cav1", "cav1 may regulate", "may regulate virus uptake", "regulate virus uptake as", "virus uptake as well", "uptake as well as", "as well as the", "well as the trafficking", "as the trafficking of", "the trafficking of viral", "trafficking of viral structural", "of viral structural proteins", "structural proteins inferred", "proteins inferred from", "inferred from the orthologous", "from the orthologous protein", "the orthologous protein in", "orthologous protein in sars", "protein in sars cov", "in sars cov 1", "sars cov 1 .", "severe acute respiratory syndrome coronavirus", "acute respiratory syndrome coronavirus type", "respiratory syndrome coronavirus type 2", "coronavirus type 2 sars\u2011cov\u20112", "2 sars\u2011cov\u20112 encodes", "sars\u2011cov\u20112 encodes several proteins", "encodes several proteins that modulate", "several proteins that modulate host", "proteins that modulate host intracellular", "that modulate host intracellular signaling", "modulate host intracellular signaling and", "host intracellular signaling and regulatory", "intracellular signaling and regulatory pathways.", "signaling and regulatory pathways. among", "and regulatory pathways. among them", "regulatory pathways. among them are", "pathways. among them are membrane", "among them are membrane m", "are membrane m nucleocapsid", "membrane m nucleocapsid n", "m nucleocapsid n and", "nucleocapsid n and 3a proteins", "n and 3a proteins that", "and 3a proteins that directly", "3a proteins that directly bind", "proteins that directly bind to", "that directly bind to host", "directly bind to host targets", "bind to host targets associated", "to host targets associated with", "host targets associated with sars\u2011cov\u20112", "targets associated with sars\u2011cov\u20112 infection", "associated with sars\u2011cov\u20112 infection and", "with sars\u2011cov\u20112 infection and cytokine", "sars\u2011cov\u20112 infection and cytokine production.", "infection and cytokine production. this", "and cytokine production. this reactome", "cytokine production. this reactome module", "production. this reactome module describes", "this reactome module describes several", "reactome module describes several such", "module describes several such binding", "describes several such binding events", "several such binding events and", "such binding events and their", "binding events and their consequences.", "events and their consequences. first", "their consequences. first sars\u2011cov\u20112", "consequences. first sars\u2011cov\u20112 m", "first sars\u2011cov\u20112 m binds", "sars\u2011cov\u20112 m binds to 3\u2011phosphoinositide\u2011dependent", "m binds to 3\u2011phosphoinositide\u2011dependent protein", "binds to 3\u2011phosphoinositide\u2011dependent protein kinase", "to 3\u2011phosphoinositide\u2011dependent protein kinase 1", "protein kinase 1 pdpk1", "1 pdpk1 to", "pdpk1 to inhibit pkb/akt", "inhibit pkb/akt activation ren", "pkb/akt activation ren y", "activation ren y et", "ren y et al. 2021", "y et al. 2021 .", "et al. 2021 . second", "2021 . second sars\u2011cov\u20111", ". second sars\u2011cov\u20111 n", "second sars\u2011cov\u20111 n binds", "sars\u2011cov\u20111 n binds to the", "n binds to the host", "binds to the host 14", "to the host 14 3", "the host 14 3 3", "host 14 3 3 protein", "3 3 protein which", "3 protein which regulates", "protein which regulates nucleocytoplasmic", "which regulates nucleocytoplasmic shuttling and", "regulates nucleocytoplasmic shuttling and other", "nucleocytoplasmic shuttling and other functions", "shuttling and other functions of", "and other functions of n", "functions of n tugaeva", "of n tugaeva kv", "n tugaeva kv et", "tugaeva kv et al. 2021", "kv et al. 2021 .", "et al. 2021 . third", "2021 . third binding", ". third binding of", "third binding of viral", "binding of viral 3a to", "of viral 3a to the", "viral 3a to the regulator", "3a to the regulator and", "to the regulator and scaffolding", "the regulator and scaffolding protein", "regulator and scaffolding protein caveolin\u20111", "scaffolding protein caveolin\u20111 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              this", "al. 2019 .

              this reactome", "2019 .

              this reactome module", ".

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"liu t et al. 2017", "et al. 2017 yu", "al. 2017 yu h", "2017 yu h et", "h et al. 2020 .", "et al. 2020 . in", "al. 2020 . in unstimulated", "2020 . in unstimulated cells", "in unstimulated cells nf", "unstimulated cells nf \u03bab", "cells nf \u03bab is", "nf \u03bab is sequestered in", "\u03bab is sequestered in the", "is sequestered in the cytosol", "sequestered in the cytosol through", "in the cytosol through interactions", "the cytosol through interactions with", "cytosol through interactions with a", "through interactions with a class", "interactions with a class of", "with a class of inhibitor", "a class of inhibitor proteins", "of inhibitor proteins called", "inhibitor proteins called nf", "proteins called nf \u03bab", "nf \u03bab inhibitors ikbs", "inhibitors ikbs such", "ikbs such as nfkbia", "such as nfkbia or nfkbib", "or nfkbib jacobs", "nfkbib jacobs md", "jacobs md & harrison sc", "md & harrison sc 1998", "& harrison sc 1998 .", "harrison sc 1998 . ikbs", "sc 1998 . ikbs 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              this reactome module", "2019 .

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              this", ".

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              this reactome", ".

              this reactome module", "

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              this", "2022 .

              this reactome module", ".

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"differentiation by", "by ebf2", "transcriptional regulation of", "regulation of brown", "of brown and", "brown and beige", "and beige adipocyte", "beige adipocyte differentiation", "adipocyte differentiation by", "differentiation by ebf2", "transcriptional regulation of brown", "regulation of brown and", "of brown and beige", "brown and beige adipocyte", "and beige adipocyte differentiation", "beige adipocyte differentiation by", "adipocyte differentiation by ebf2", "transcriptional regulation of brown and", "regulation of brown and beige", "of brown and beige adipocyte", "brown and beige adipocyte differentiation", "and beige adipocyte differentiation by", "beige adipocyte differentiation by ebf2", "early b", "b cell", "cell factor", "factor 2", "is a", "a transcription", "transcription factor", "factor that", "that marks", "marks committed", "committed brown", "beige preadipocytes.", "preadipocytes. ebf2", "ebf2 cooperates", "cooperates with", "with pparg", "a master", "master regulator", "regulator of", "of adipogenesis", "to activate", "activate the", "the brown/beige", "brown/beige adipocyte", "adipocyte thermogenic", "thermogenic program", "inferred from", "from mouse", "mouse homologs", "homologs in", "in rajakumari", "rajakumari et", "et al.", "al. 2013", "2013 .", ". in", "in white", "white adipocytes", "the activity", "activity of", "of ebf2", "ebf2 is", "is negatively", "negatively regulated", "regulated by", "by binding", "binding of", "of the", "the transcription", "factor znf423", "a key", "key transcription", "factor for", "for white", "white adipocyte", "adipocyte differentiation.", "differentiation. in", "in brown/beige", "brown/beige fate", "fate committed", "committed cells", "the interaction", "interaction between", "between znf423", "znf423 and", "and ebf2", "is impeded", "impeded by", "by bmp7", "which acts", "acts as", "as a", "a positive", "positive regulator", "of brown/beige", "brown/beige adipogenesis", "in shao", "shao et", "al. 2016", "al. 2021", "2021 .", ". direct", "direct transcriptional", "transcriptional targets", "targets of", "ebf2 include", "include prdm16", "and ppara", "ppara genes.", "genes. other", "other marker", "marker genes", "genes of", "brown/beige adipocytes", "such as", "as cidea", "and dio2", "dio2 are", "are positively", "positively regulated", "ebf2 and", "and probably", "probably also", "also direct", "direct targets", "wang et", "al. 2014", "stine et", "shapira et", "al. 2017", "lai et", "angueira et", "al. 2020", "2020 .", ". based", "based on", "on mouse", "mouse studies", "ebf1 may", "may function", "function partially", "partially redundantly", "redundantly with", "with ebf2", "ebf2 in", "in regulation", "of thermogenesis", "thermogenesis genes", ". transcriptional", "transcriptional activity", "is positively", "the long", "long noncoding", "noncoding rna", "in zhao", "zhao et", "mi et", "2017 .", "ebf2 was", "was reported", "reported to", "to recruit", "recruit the", "the baf", "baf chromatin", "chromatin remodeling", "remodeling complex", "complex to", "transcription of", "of target", "target genes", "liu et", "in addition", "addition to", "to pparg", "to cooperate", "cooperate with", "with other", "other transcription", "transcription factors", "factors such", "as six1", "six1 during", "during brown/beige", "brunmeir et", "2016 .", ". besides", "besides znf423", "as id1", "patil et", "and tle3", "pearson et", "al. 2019", "have been", "been reported", "to act", "act as", "as inhibitors", "inhibitors of", "ebf2 mediated", "mediated transcription.", "transcription. the", "factor gata6", "gata6 was", "to directly", "directly stimulate", "stimulate ebf2", "ebf2 transcription", "transcription during", "during mouse", "mouse beige/brown", "beige/brown thermogenesis", "jun et", "al. 2023", "2023 .", "besides bpm7", "bpm9 mediated", "mediated upregulation", "upregulation of", "of fgfr3", "yamamoto et", "al. 2022", "and fgf11", "jiang et", "reported as", "as indirect", "indirect activators", "activators of", "ebf2 transcriptional", "activity in", "in mouse", "mouse and", "and goat", "respectively. zag", "zinc alpha2", "alpha2 glycoprotein", "a tumor", "tumor secretory", "secretory factor", "has been", "to stimulate", "ebf2 expression", "which contributes", "contributes to", "to white", "white adipose", "adipose tissue", "tissue browning", "browning and", "and energy", "energy wasting", "wasting in", "in cancer", "cancer related", "related cachexia", "elattar et", "al. 2018", "2018 .", "in the", "the single", "single cell", "cell atlas", "atlas of", "of human", "human white", "emont et", "it was", "reported that", "that the", "the ebf2", "ebf2 positive", "positive had6", "had6 white", "adipocyte subpopulation", "subpopulation with", "with ucp1", "ucp1 expression", "consistent with", "with the", "the beige", "beige profile", "shows an", "an association", "association with", "with increased", "increased bmi", "bmi and", "and visceral", "visceral adiposity.", "adiposity. for", "for review", "please refer", "refer to", "to wang", "wang and", "and seale", "seale 2016.", "ebf2 early", "early b cell", "b cell factor", "cell factor 2", "2 is", "is a transcription", "a transcription factor", "transcription factor that", "factor that marks", "that marks committed", "marks committed brown", "committed brown and", "and beige preadipocytes.", "beige preadipocytes. ebf2", "preadipocytes. ebf2 cooperates", "ebf2 cooperates with", "cooperates with pparg", "pparg a", "a master regulator", "master regulator of", "regulator of adipogenesis", "adipogenesis to", "to activate the", "activate the brown/beige", "the brown/beige adipocyte", "brown/beige adipocyte thermogenic", "adipocyte thermogenic program", "program inferred", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in rajakumari", "in rajakumari et", "rajakumari et al.", "et al. 2013", "al. 2013 .", "2013 . in", ". in white", "in white adipocytes", 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"in shao et", "shao et al.", "et al. 2016", "2016 shao", "et al. 2021", "al. 2021 .", "2021 . direct", ". direct transcriptional", "direct transcriptional targets", "transcriptional targets of", "targets of ebf2", "of ebf2 include", "ebf2 include prdm16", "prdm16 ucp1", "ucp1 and", "and ppara genes.", "ppara genes. other", "genes. other marker", "other marker genes", "marker genes of", "genes of brown/beige", "of brown/beige adipocytes", "adipocytes such", "such as cidea", "cidea ppargc1a", "ppargc1a cox7a", "cox7a and", "and dio2 are", "dio2 are positively", "are positively regulated", "positively regulated by", "regulated by ebf2", "by ebf2 and", "ebf2 and probably", "and probably also", "probably also direct", "also direct targets", "direct targets of", "ebf2 inferred", "2013 wang", "wang et al.", "et al. 2014", "2014 stine", "stine et al.", "2016 shapira", "shapira et al.", "et al. 2017", "2017 lai", "lai et al.", "2017 angueira", "angueira et al.", "et al. 2020", "al. 2020 .", "2020 . based", ". based on", "based on mouse", "on mouse studies", "studies ebf1", "ebf1 may function", "may function partially", "function partially redundantly", "partially redundantly with", "redundantly with ebf2", "with ebf2 in", "ebf2 in regulation", "in regulation of", "regulation of thermogenesis", "of thermogenesis genes", "genes angueira", "2020 . transcriptional", ". transcriptional activity", "transcriptional activity of", "ebf2 is positively", "is positively regulated", "of the long", "the long noncoding", "long noncoding rna", "rna lncrna", "lncrna blnc1", "blnc1 inferred", "homologs in zhao", "in zhao et", "zhao et al.", "2014 mi", "mi et al.", "al. 2017 .", "2017 . based", "studies ebf2", "ebf2 was reported", "was reported to", "reported to recruit", "to recruit the", "recruit the baf", "the baf chromatin", "baf chromatin remodeling", "chromatin remodeling complex", "remodeling complex to", "complex to activate", "activate the transcription", "the transcription of", "transcription of target", "of target genes", "genes shapira", "2017 liu", "liu et al.", "2020 . in", ". in addition", "in addition to", "addition to pparg", "pparg based", "reported to cooperate", "to cooperate with", "cooperate with other", "with other transcription", "other transcription factors", "transcription factors such", "factors such as", "such as six1", "as six1 during", "six1 during brown/beige", "during brown/beige adipogenesis", "adipogenesis brunmeir", "brunmeir et al.", "al. 2016 .", "2016 . besides", ". besides znf423", "znf423 based", "studies other", "such as id1", "id1 patil", "patil et al.", "2017 and", "tle3 pearson", "pearson et al.", "et al. 2019", "have been reported", "been reported to", "reported to act", "to act as", "act as inhibitors", "as inhibitors of", "inhibitors of ebf2", "of ebf2 mediated", "ebf2 mediated transcription.", "mediated transcription. the", "transcription. the transcription", "transcription factor gata6", "factor gata6 was", "gata6 was reported", "reported to directly", "to directly stimulate", "directly stimulate ebf2", "stimulate ebf2 transcription", "ebf2 transcription during", "transcription during mouse", "during mouse beige/brown", "mouse beige/brown thermogenesis", "thermogenesis jun", "jun et al.", "et al. 2023", "al. 2023 .", "2023 . besides", ". besides bpm7", "bpm7 bpm9", "bpm9 mediated upregulation", "mediated upregulation of", "upregulation of fgfr3", "fgfr3 yamamoto", "yamamoto et al.", "et al. 2022", "fgf11 jiang", "jiang et al.", "2023 have", "been reported as", "reported as indirect", "as indirect activators", "indirect activators of", "activators of ebf2", "of ebf2 transcriptional", "ebf2 transcriptional activity", "transcriptional activity in", "activity in mouse", "in mouse and", "mouse and goat", "goat respectively.", "zag zinc", "zinc alpha2 glycoprotein", "a tumor secretory", "tumor secretory factor", "factor has", "has been reported", "reported to stimulate", "to stimulate ebf2", "stimulate ebf2 expression", "expression which", "which contributes to", "contributes to white", "to white adipose", "white adipose tissue", "adipose tissue browning", "tissue browning and", "browning and energy", "and energy wasting", "energy wasting in", "wasting in cancer", "in cancer related", "cancer related cachexia", "cachexia elattar", "elattar et al.", "et al. 2018", "al. 2018 .", "2018 . in", ". in the", "in the single", "the single cell", "single cell atlas", "cell atlas of", "atlas of human", "of human white", "human white adipose", "tissue emont", "emont et al.", "2022 it", "it was reported", "was reported that", "reported that the", "that the ebf2", "the ebf2 positive", "ebf2 positive had6", "positive had6 white", "had6 white adipocyte", "white adipocyte subpopulation", "adipocyte subpopulation with", "subpopulation with ucp1", "with ucp1 expression", "expression consistent", "consistent with the", "with the beige", "the beige profile", "profile shows", "shows an association", "an association with", "association with increased", "with increased bmi", "increased bmi and", "bmi and visceral", "and visceral adiposity.", "visceral adiposity. for", "adiposity. for review", "review please", "please refer to", "refer to wang", "to wang and", "wang and seale", "and seale 2016.", "ebf2 early b", "early b cell factor", "b cell factor 2", "factor 2 is", "2 is a", "is a transcription factor", "a transcription factor that", "transcription factor that marks", "factor that marks committed", "that marks committed brown", "marks committed brown and", "committed brown and beige", "brown and beige preadipocytes.", "and beige preadipocytes. ebf2", "beige preadipocytes. ebf2 cooperates", "preadipocytes. ebf2 cooperates with", "ebf2 cooperates with pparg", "with pparg a", "pparg a master", "a master regulator of", "master regulator of adipogenesis", "of adipogenesis to", "adipogenesis to activate", "to activate the brown/beige", "activate the brown/beige adipocyte", "the brown/beige adipocyte thermogenic", "brown/beige adipocyte thermogenic program", "thermogenic program inferred", "program inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in rajakumari", "homologs in rajakumari et", "in rajakumari et al.", "rajakumari et al. 2013", "et al. 2013 .", "al. 2013 . in", "2013 . in white", ". in white adipocytes", "white adipocytes the", "adipocytes the activity", "the activity of ebf2", "activity of ebf2 is", "of ebf2 is negatively", "ebf2 is negatively regulated", "is negatively regulated by", "negatively regulated by binding", "regulated by binding of", "by binding of the", "binding of the transcription", "of the transcription factor", "the transcription factor znf423", "factor znf423 a", "znf423 a key", "a key transcription factor", "key transcription factor for", "transcription factor for white", "factor for white adipocyte", "for white adipocyte differentiation.", "white adipocyte differentiation. in", "adipocyte differentiation. in brown/beige", "differentiation. in brown/beige fate", "in brown/beige fate committed", "brown/beige fate committed cells", "committed cells the", "cells the interaction", "the interaction between znf423", "interaction between znf423 and", "between znf423 and ebf2", "znf423 and ebf2 is", "and ebf2 is impeded", "ebf2 is impeded by", "is impeded by bmp7", "by bmp7 which", "bmp7 which acts", "which acts as a", "acts as a positive", "as a positive regulator", "a positive regulator of", "positive regulator of brown/beige", "regulator of brown/beige adipogenesis", "brown/beige adipogenesis inferred", "adipogenesis inferred from", "mouse homologs in shao", "homologs in shao et", "in shao et al.", "shao et al. 2016", "al. 2016 shao", "2016 shao et", "shao et al. 2021", "et al. 2021 .", "al. 2021 . direct", "2021 . direct transcriptional", ". direct transcriptional targets", "direct transcriptional targets of", "transcriptional targets of ebf2", "targets of ebf2 include", "of ebf2 include prdm16", "include prdm16 ucp1", "ucp1 and ppara", "and ppara genes. other", "ppara genes. other marker", "genes. other marker genes", "other marker genes of", "marker genes of brown/beige", "genes of brown/beige adipocytes", "brown/beige adipocytes such", "adipocytes such as", "as cidea ppargc1a", "cox7a and dio2", "and dio2 are positively", "dio2 are positively regulated", "are positively regulated by", "positively regulated by ebf2", "regulated by ebf2 and", "by ebf2 and probably", "ebf2 and probably also", "and probably also direct", "probably also direct targets", "also direct targets of", "direct targets of ebf2", "of ebf2 inferred", "ebf2 inferred from", "al. 2013 wang", "2013 wang et", "wang et al. 2014", "al. 2014 stine", "2014 stine et", "stine et al. 2016", "al. 2016 shapira", "2016 shapira et", "shapira et al. 2017", "al. 2017 lai", "2017 lai et", "lai et al. 2017", "al. 2017 angueira", "2017 angueira et", "angueira et al. 2020", "et al. 2020 .", "al. 2020 . based", "2020 . based on", ". based on mouse", "based on mouse studies", "mouse studies ebf1", "studies ebf1 may", "ebf1 may function partially", "may function partially redundantly", "function partially redundantly with", "partially redundantly with ebf2", "redundantly with ebf2 in", "with ebf2 in regulation", "ebf2 in regulation of", "in regulation of thermogenesis", "regulation of thermogenesis genes", "thermogenesis genes angueira", "genes angueira et", "al. 2020 . transcriptional", "2020 . transcriptional activity", ". transcriptional activity of", "transcriptional activity of ebf2", "of ebf2 is positively", "ebf2 is positively regulated", "is positively regulated by", "positively regulated by binding", "binding of the long", "of the long noncoding", "the long noncoding rna", "noncoding rna lncrna", "blnc1 inferred from", "mouse homologs in zhao", "homologs in zhao et", "in zhao et al.", "zhao et al. 2014", "al. 2014 mi", "2014 mi et", "mi et al. 2017", "et al. 2017 .", "al. 2017 . based", "2017 . based on", "mouse studies ebf2", "studies ebf2 was", "ebf2 was reported to", "was reported to recruit", "reported to recruit the", "to recruit the baf", "recruit the baf chromatin", "the baf chromatin remodeling", "baf chromatin remodeling complex", "chromatin remodeling complex to", "remodeling complex to activate", "complex to activate the", "to activate the transcription", "activate the transcription of", "the transcription of target", "transcription of target genes", "target genes shapira", "genes shapira et", "al. 2017 liu", "2017 liu et", "liu et al. 2020", "al. 2020 . in", "2020 . in addition", ". in addition to", "in addition to pparg", "to pparg based", "pparg based on", "was reported to cooperate", "reported to cooperate with", "to cooperate with other", "cooperate with other transcription", "with other transcription factors", "other transcription factors such", "transcription factors such as", "factors such as six1", "such as six1 during", "as six1 during brown/beige", "six1 during brown/beige adipogenesis", "brown/beige adipogenesis brunmeir", "adipogenesis brunmeir et", "brunmeir et al. 2016", "et al. 2016 .", "al. 2016 . besides", "2016 . besides znf423", "besides znf423 based", "znf423 based on", "mouse studies other", "studies other transcription", "as id1 patil", "id1 patil et", "patil et al. 2017", "al. 2017 and", "2017 and tle3", "and tle3 pearson", "tle3 pearson et", "pearson et al. 2019", "2019 have", "have been reported to", "been reported to act", "reported to act as", "to act as inhibitors", "act as inhibitors of", "as inhibitors of ebf2", "inhibitors of ebf2 mediated", "of ebf2 mediated transcription.", "ebf2 mediated transcription. the", "mediated transcription. the transcription", "transcription. the transcription factor", "the transcription factor gata6", "transcription factor gata6 was", "factor gata6 was reported", "gata6 was reported to", "was reported to directly", "reported to directly stimulate", "to directly stimulate ebf2", "directly stimulate ebf2 transcription", "stimulate ebf2 transcription during", "ebf2 transcription during mouse", "transcription during mouse beige/brown", "during mouse beige/brown thermogenesis", "beige/brown thermogenesis jun", "thermogenesis jun et", "jun et al. 2023", "et al. 2023 .", "al. 2023 . besides", "2023 . besides bpm7", "besides bpm7 bpm9", "bpm7 bpm9 mediated", "bpm9 mediated upregulation of", "mediated upregulation of fgfr3", "of fgfr3 yamamoto", "fgfr3 yamamoto et", "yamamoto et al. 2022", "2022 and", "and fgf11 jiang", "fgf11 jiang et", "jiang et al. 2023", "al. 2023 have", "2023 have been", "have been reported as", "been reported as indirect", "reported as indirect activators", "as indirect activators of", "indirect activators of ebf2", "activators of ebf2 transcriptional", "of ebf2 transcriptional activity", "ebf2 transcriptional activity in", "transcriptional activity in mouse", "activity in mouse and", "in mouse and goat", "and goat respectively.", "goat respectively. zag", "respectively. zag zinc", "zag zinc alpha2", "glycoprotein a", "a tumor secretory factor", "secretory factor has", "factor has been", "has been reported to", "been reported to stimulate", "reported to stimulate ebf2", "to stimulate ebf2 expression", "ebf2 expression which", "expression which contributes", "which contributes to white", "contributes to white adipose", "to white adipose tissue", "white adipose tissue browning", "adipose tissue browning and", "tissue browning and energy", "browning and energy wasting", "and energy wasting in", "energy wasting in cancer", "wasting in cancer related", "in cancer related cachexia", "related cachexia elattar", "cachexia elattar et", "elattar et al. 2018", "et al. 2018 .", "al. 2018 . in", "2018 . in the", ". in the single", "in the single cell", "the single cell atlas", "single cell atlas of", "cell atlas of human", "atlas of human white", "of human white adipose", "human white adipose tissue", "adipose tissue emont", "tissue emont et", "emont et al. 2022", "al. 2022 it", "2022 it was", "it was reported that", "was reported that the", "reported that the ebf2", "that the ebf2 positive", "the ebf2 positive had6", "ebf2 positive had6 white", "positive had6 white adipocyte", "had6 white adipocyte subpopulation", "white adipocyte subpopulation with", "adipocyte subpopulation with ucp1", "subpopulation with ucp1 expression", "ucp1 expression consistent", "expression consistent with", "consistent with the beige", "with the beige profile", "beige profile shows", "profile shows an", "shows an association with", "an association with increased", "association with increased bmi", "with increased bmi and", "increased bmi and visceral", "bmi and visceral adiposity.", "and visceral adiposity. for", "visceral adiposity. for review", "for review please", "review please refer", "please refer to wang", "refer to wang and", "to wang and seale", "wang and seale 2016.", "ebf2 early b cell", "early b cell factor 2", "cell factor 2 is", "factor 2 is a", "2 is a transcription", "is a transcription factor that", "a transcription factor that marks", "transcription factor that marks committed", "factor that marks committed brown", "that marks committed brown and", "marks committed brown and beige", "committed brown and beige preadipocytes.", "brown and beige preadipocytes. ebf2", "and beige preadipocytes. ebf2 cooperates", "beige preadipocytes. ebf2 cooperates with", "preadipocytes. ebf2 cooperates with pparg", "cooperates with pparg a", "with pparg a master", "pparg a master regulator", "a master regulator of adipogenesis", "regulator of adipogenesis to", "of adipogenesis to activate", "adipogenesis to activate the", "to activate the brown/beige adipocyte", "activate the brown/beige adipocyte thermogenic", "the brown/beige adipocyte thermogenic program", "adipocyte thermogenic program inferred", "thermogenic program inferred from", "program inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in rajakumari", "mouse homologs in rajakumari et", "homologs in rajakumari et al.", "in rajakumari et al. 2013", "rajakumari et al. 2013 .", "et al. 2013 . in", "al. 2013 . in white", "2013 . in white adipocytes", "in white adipocytes the", "white adipocytes the activity", "adipocytes the activity of", "the activity of ebf2 is", "activity of ebf2 is negatively", "of ebf2 is negatively regulated", "ebf2 is negatively regulated by", "is negatively regulated by binding", "negatively regulated by binding of", "regulated by binding of the", "by binding of the transcription", "binding of the transcription factor", "of the transcription factor znf423", "transcription factor znf423 a", "factor znf423 a key", "znf423 a key transcription", "a key transcription factor for", "key transcription factor for white", "transcription factor for white adipocyte", "factor for white adipocyte differentiation.", "for white adipocyte differentiation. in", "white adipocyte differentiation. in brown/beige", "adipocyte differentiation. in brown/beige fate", "differentiation. in brown/beige fate committed", "in brown/beige fate committed cells", "fate committed cells the", "committed cells the interaction", "cells the interaction between", "the interaction between znf423 and", "interaction between znf423 and ebf2", "between znf423 and ebf2 is", "znf423 and ebf2 is impeded", "and ebf2 is impeded by", "ebf2 is impeded by bmp7", "impeded by bmp7 which", "by bmp7 which acts", "bmp7 which acts as", "which acts as a positive", "acts as a positive regulator", "as a positive regulator of", "a positive regulator of brown/beige", "positive regulator of brown/beige adipogenesis", "of brown/beige adipogenesis inferred", "brown/beige adipogenesis inferred from", "adipogenesis inferred from mouse", "from mouse homologs in shao", "mouse homologs in shao et", "homologs in shao et al.", "in shao et al. 2016", "et al. 2016 shao", "al. 2016 shao et", "2016 shao et al.", "shao et al. 2021 .", "et al. 2021 . direct", "al. 2021 . direct transcriptional", "2021 . direct transcriptional targets", ". direct transcriptional targets of", "direct transcriptional targets of ebf2", "transcriptional targets of ebf2 include", "targets of ebf2 include prdm16", "ebf2 include prdm16 ucp1", "prdm16 ucp1 and", "ucp1 and ppara genes.", "and ppara genes. other marker", "ppara genes. other marker genes", "genes. other marker genes of", "other marker genes of brown/beige", "marker genes of brown/beige adipocytes", "of brown/beige adipocytes such", "brown/beige adipocytes such as", "adipocytes such as cidea", "such as cidea ppargc1a", "cidea ppargc1a cox7a", "ppargc1a cox7a and", "cox7a and dio2 are", "and dio2 are positively regulated", "dio2 are positively regulated by", "are positively regulated by ebf2", "positively regulated by ebf2 and", "regulated by ebf2 and probably", "by ebf2 and probably also", "ebf2 and probably also direct", "and probably also direct targets", "probably also direct targets of", "also direct targets of ebf2", "targets of ebf2 inferred", "of ebf2 inferred from", "ebf2 inferred from mouse", "et al. 2013 wang", "al. 2013 wang et", "2013 wang et al.", "et al. 2014 stine", "al. 2014 stine et", "2014 stine et al.", "et al. 2016 shapira", "al. 2016 shapira et", "2016 shapira et al.", "et al. 2017 lai", "al. 2017 lai et", "2017 lai et al.", "et al. 2017 angueira", "al. 2017 angueira et", "2017 angueira et al.", "angueira et al. 2020 .", "et al. 2020 . based", "al. 2020 . based on", "2020 . based on mouse", ". based on mouse studies", "on mouse studies ebf1", "mouse studies ebf1 may", "studies ebf1 may function", "ebf1 may function partially redundantly", "may function partially redundantly with", "function partially redundantly with ebf2", "partially redundantly with ebf2 in", "redundantly with ebf2 in regulation", "with ebf2 in regulation of", "ebf2 in regulation of thermogenesis", "in regulation of thermogenesis genes", "of 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transcription factors such", "other transcription factors such as", "transcription factors such as six1", "factors such as six1 during", "such as six1 during brown/beige", "as six1 during brown/beige adipogenesis", "during brown/beige adipogenesis brunmeir", "brown/beige adipogenesis brunmeir et", "adipogenesis brunmeir et al.", "brunmeir et al. 2016 .", "et al. 2016 . besides", "al. 2016 . besides znf423", ". besides znf423 based", "besides znf423 based on", "znf423 based on mouse", "on mouse studies other", "mouse studies other transcription", "studies other transcription factors", "factors such as id1", "such as id1 patil", "as id1 patil et", "id1 patil et al.", "et al. 2017 and", "al. 2017 and tle3", "and tle3 pearson et", "tle3 pearson et al.", "al. 2019 have", "2019 have been", "have been reported to act", "been reported to act as", "reported to act as inhibitors", "to act as inhibitors of", "act as inhibitors of ebf2", "as inhibitors of ebf2 mediated", "inhibitors of ebf2 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              generation", "al. 1998 .

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"associated protein 33b", "33b vps33b", "deghmane et al.", "et al. 2007", "2007 bach", "bach et al.", "al. 2008 .", "2008 . also", ". also the", "also the ras", "the ras related", "ras related protein", "protein rab5", "rab5 effector", "effector phosphatidylinositol 3", "phosphatidylinositol 3 phosphate", "phosphate pi3p", "pi3p gets", "gets enzymatically depleted", "depleted vergne", "vergne et al.", "et al. 2005", "al. 2005 .", "lam is transported", "is transported to mtb's", "transported to mtb's outer", "to mtb's outer cell", "mtb's outer cell wall.", "outer cell wall. when", "cell wall. when mtb", "wall. when mtb is", "when mtb is interned", "mtb is interned by", "is interned by the", "interned by the phagocyte", "the phagocyte lam", "phagocyte lam is", "lam is shedded into", "is shedded into the", "shedded into the phagocyte's", "into the phagocyte's membrane", "phagocyte's membrane gets", "membrane gets incorporated", "gets incorporated into lipid", "incorporated into lipid 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              ogg1 r229q", "hyun et", "al. 2002", "hill and", "and evans", "evans 2007", "
              ogg1 p266fs139*", "mao et", "al. 2007", "2007 .
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              the", ".
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              ogg1", "r229q hyun", "hyun et al.", "2000 hyun", "et al. 2002", "2002 hill", "hill and evans", "and evans 2007", "2007
              ogg1", "p266fs139* mao", "mao et al.", "et al. 2007", "al. 2007 .
              ogg1", "2007 .
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              the", "2014 .
              the following", ".
              the following ogg1", "to remove fapyg:
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              ogg1", "2000 .
              ogg1 r46l", ".
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              ogg1", "2000
              ogg1 r154h", "
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              ogg1 r131q", "
              ogg1 r131q chevillard", "r131q chevillard et", "chevillard et al. 1998", "al. 1998 bruner", "1998 bruner et", "al. 2000 anderson", "2000 anderson and", "anderson and dagget 2009", "dagget 2009
              ogg1", "2009
              ogg1 r229q", "
              ogg1 r229q hyun", "r229q hyun et", "hyun et al. 2000", "al. 2000 hyun", "2000 hyun et", "hyun et al. 2002", "al. 2002 hill", "2002 hill and", "hill and evans 2007", "evans 2007
              ogg1", "2007
              ogg1 p266fs139*", "
              ogg1 p266fs139* mao", "p266fs139* mao et", "mao et al. 2007", "et al. 2007 .
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              ogg1 r46l", "2007 .
              ogg1 r46l and", ".
              ogg1 r46l and ogg1", "r46l and ogg1 r131g", "and ogg1 r131g have", "ogg1 r131g have not", "r131g have not been", "have not been functionally", "not been functionally studied", "been functionally studied but", "functionally studied but have", "studied but have been", "but have been reported", "have been reported in", "been reported in cancer", "reported in cancer and", "in cancer and predicted", "cancer and predicted to", "and predicted to be", "predicted to be pathogenic.", "to be pathogenic. they", "be pathogenic. they are", "pathogenic. they are annotated", "they are annotated as", "are annotated as candidate", "annotated as candidate disease", "as candidate disease variants", "candidate disease variants based", "disease variants based on", "variants based on their", "based on their similarity", "on their similarity with", "their similarity with ogg1", "similarity with ogg1 r46q", "with ogg1 r46q and", "ogg1 r46q and ogg1", "r46q and ogg1 r131q", "ogg1 r131q respectively.
              ogg1", "r131q respectively.
              ogg1 s326c", "respectively.
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              the", "al. 2014 .
              the following", "2014 .
              the following ogg1", ".
              the following ogg1 mutants", "ability to remove fapyg:
              ogg1", "to remove fapyg:
              ogg1 r46q", "fapyg:
              ogg1 r46q audebert", "et al. 2000 .
              ogg1", "al. 2000 .
              ogg1 r46l", "2000 .
              ogg1 r46l has", ".
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              the", "remove fapyg from dna.
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              ogg1", "ability to remove 8oxog:
              ogg1 r46q", "remove 8oxog:
              ogg1 r46q audebert", "r46q audebert chevillard", "audebert chevillard et al.", "et al. 2000 audebert", "2000 audebert radicella", "audebert radicella et al.", "et al. 2000
              ogg1", "al. 2000
              ogg1 r154h", "r154h audebert radicella", "et al. 2000 bruner", "al. 2000 bruner et", "2000 bruner et al.", "al. 2000
              ogg1 r131q", "
              ogg1 r131q chevillard et", "r131q chevillard et al.", "et al. 1998 bruner", "al. 1998 bruner et", "1998 bruner et al.", "et al. 2000 anderson", "al. 2000 anderson and", "2000 anderson and dagget", "and dagget 2009
              ogg1", "dagget 2009
              ogg1 r229q", "
              ogg1 r229q hyun et", "r229q hyun et al.", "et al. 2000 hyun", "al. 2000 hyun et", "2000 hyun et al.", "et al. 2002 hill", "al. 2002 hill and", "2002 hill and evans", "and evans 2007
              ogg1", "evans 2007
              ogg1 p266fs139*", "
              ogg1 p266fs139* mao et", "p266fs139* mao et al.", "mao et al. 2007 .
              ogg1", "et al. 2007 .
              ogg1 r46l", "al. 2007 .
              ogg1 r46l and", "2007 .
              ogg1 r46l and ogg1", ".
              ogg1 r46l and ogg1 r131g", "r46l and ogg1 r131g have", "and ogg1 r131g have not", "ogg1 r131g have not been", "r131g have not been functionally", "have not been functionally studied", "not been functionally studied but", "been functionally studied but have", "functionally studied but have been", "studied but have been reported", "but have been reported in", "have been reported in cancer", "been reported in cancer and", "reported in cancer and predicted", "in cancer and predicted to", "cancer and predicted to be", "and predicted to be pathogenic.", "predicted to be pathogenic. they", "to be pathogenic. they are", "be pathogenic. they are annotated", "pathogenic. they are annotated as", "they are annotated as candidate", "are annotated as candidate disease", "annotated as candidate disease variants", "as candidate disease variants based", "candidate disease variants based on", "disease variants based on their", "variants based on their similarity", "based on their similarity with", "on their similarity with ogg1", "their similarity with ogg1 r46q", "similarity with ogg1 r46q and", "with ogg1 r46q and ogg1", "ogg1 r46q and ogg1 r131q", "and ogg1 r131q respectively.
              ogg1", "ogg1 r131q respectively.
              ogg1 s326c", "respectively.
              ogg1 s326c a frequent", "s326c a frequent variant", "a frequent variant in european", "frequent variant in european and", "variant in european and asian", "in european and asian populations", "and asian populations is", "asian populations is susceptible", "populations is susceptible to", "susceptible to oxidation which", "to oxidation which diminishes", "oxidation which diminishes catalytic", "which diminishes catalytic activity under", "diminishes catalytic activity under conditions", "catalytic activity under conditions of", "activity under conditions of oxidative", "under conditions of oxidative stress", "of oxidative stress dherin", "oxidative stress dherin et", "stress dherin et al.", "et al. 1999 yamane", "al. 1999 yamane et", "1999 yamane et al.", "et al. 2004 kershaw", "al. 2004 kershaw and", "2004 kershaw and hodges", "and hodges 2012 moritz", "hodges 2012 moritz et", "2012 moritz et al.", "moritz et al. 2014 .
              the", "et al. 2014 .
              the following", "al. 2014 .
              the following ogg1", "2014 .
              the following ogg1 mutants", ".
              the following ogg1 mutants show", "their ability to remove fapyg:
              ogg1", "ability to remove fapyg:
              ogg1 r46q", "remove fapyg:
              ogg1 r46q audebert", "r46q audebert radicella", "radicella et al. 2000 .
              ogg1", "et al. 2000 .
              ogg1 r46l", "al. 2000 .
              ogg1 r46l has", "2000 .
              ogg1 r46l has not", ".
              ogg1 r46l has not been", "r46l has not been functionally", "has not been functionally studied", "been functionally studied but has", "functionally studied but has been", "studied but has been reported", "but has been reported in", "has been reported in cancer", "predicted to be pathogenic. it", "to be pathogenic. it is", "be pathogenic. it is annotated", "pathogenic. it is annotated as", "it is annotated as a", "is annotated as a candidate", "annotated as a candidate disease", "as a candidate disease variant", "a candidate disease variant for", "candidate disease variant for fapyg", "disease variant for fapyg excision", "for fapyg excision based", "fapyg excision based on", "excision based on its", "based on its similarity with", "on its similarity with ogg1", "its similarity with ogg1 r46q." ] }, { "record_id": "GLY_000594_1_1897", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9664565", "r hsa", "hsa 9664565", "r hsa 9664565" ] }, { "record_id": "GLY_000594_1_1897", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by erbb2", "erbb2 kd", "kd mutants", "signaling by erbb2", "by erbb2 kd", "erbb2 kd mutants", "signaling by erbb2 kd", "by erbb2 kd mutants", "signaling by erbb2 kd mutants", "mutations in", "in the", "the kinase", "kinase domain", "of erbb2", "erbb2 result", "result in", "in constitutive", "constitutive activation", "activation of", "erbb2 signaling", "facilitate heterodimerization", "heterodimerization of", "erbb2 with", "with other", "other egfr", "egfr family", "family members", "members and", "and increase", "increase the", "the signaling", "signaling intensity", "leading to", "to cellular", "cellular transformation", "kancha et", "et al.", "al. 2011", "2011 .
              only", ".
              only a", "a subset", "subset of", "of potential", "potential heterodimerization", "heterodimerization partners", "partners has", "has been", "been tested", "tested for", "for most", "most erbb2", "kd mutant", "mutant proteins", "so our", "our annotations", "annotations here", "here are", "are correspondingly", "correspondingly limited.", "limited. erbb2", "erbb2 l755s", "l755s and", "and erbb2", "erbb2 v777l", "v777l cancer", "cancer variants", "variants were", "were shown", "shown to", "to heterodimerize", "heterodimerize with", "with erbb3", "at a", "a higher", "higher rate", "rate than", "than wild", "wild type", "type erbb2", "croessmann et", "al. 2019", "2019 .", ". increased", "increased activity", "activity of", "erbb2 l755p", "erbb2 d769h", "erbb2 d769y", "erbb2 v842i", "erbb2 r896c", "r896c and", "erbb2 g778_p780dup", "g778_p780dup in", "the presence", "presence of", "of either", "either egfr", "bose et", "al. 2013", "or erbb3", "collier et", "as a", "a heterodimerization", "heterodimerization partner", "partner was", "was also", "also observed.", "observed. the", "the interplay", "interplay of", "erbb2 i767m", "i767m and", "r896c with", "erbb3 has", "has not", "not been", "been tested.", "tested. erbb2", "erbb2 l869r", "l869r mutant", "mutant shows", "shows increased", "activity in", "of erbb3", "which is", "is further", "further augmented", "augmented in", "of dimerization", "dimerization facilitating", "facilitating erbb3", "erbb3 e928g", "e928g mutants", "hanker et", "al. 2017", "2017 .", ". the", "l869r with", "with egfr", "egfr has", "tested. heterodimerization", "mutants with", "with erbb4", "erbb4 has", "tested and", "and erbb4", "erbb4 is", "is a", "a candidate", "candidate heterodimerization", "partner for", "for these", "these kd", "kd variants.
              erbb2", "variants.
              erbb2 h878y", "h878y mutant", "mutant has", "has ten", "ten times", "times higher", "higher kinase", "kinase activity", "activity than", "than the", "the wild", "wan et", "al. 2015", "hu et", "but its", "its heterodimerization", "heterodimerization properties", "properties have", "have not", "been studied", "studied and", "and it", "it is", "is therefore", "therefore annotated", "annotated as", "a candidate.
              ", "candidate.
              ligand", "ligand requirements", "requirements have", "studied in", "the context", "context of", "of heterodimerization", "but it", "is assumed", "assumed that", "that ligands", "ligands are", "are required.
              ", "required.
              the", "signaling properties", "properties of", "erbb2 l755m", "gonzalez alonso", "alonso et", "erbb2 l755w", "cosmic database:", "database: forbes", "forbes et", "erbb2 v777e", "dietz et", "erbb2 v777m", "lee et", "al. 2006", "ross et", "al. 2016", "zehir et", "erbb2 d769n", "tschui et", "erbb2 v842e", "siroy et", "erbb2 r896h", "cancer genome", "genome atlas", "atlas research", "research network", "network 2011", "erbb2 l869q", "erbb2 h878r", "trowe et", "al. 2008", "been experimentally", "experimentally tested", "but they", "they are", "are predicted", "predicted to", "to be", "be pathogenic", "and they", "are annotated", "as candidates.", "candidates. erbb2", "erbb2 t733i", "erbb2 t798i", "erbb2 t798m", "usually occur", "occur as", "as secondary", "secondary erbb2", "erbb2 mutations", "mutations and", "and are", "are responsible", "responsible for", "for treatment", "treatment failure.", "failure. on", "on their", "their own", "t733i and", "t798i appear", "appear to", "be weakly", "weakly transforming", "transforming compared", "compared with", "with the", "the other", "other erbb2", "kd mutants.", "mutants. as", "as their", "their signaling", "have been", "been poorly", "poorly studied", "t798i and", "t798m are", "as candidates.
              the", "candidates.
              the binding", "binding of", "mutants to", "to erbin", "erbin and", "and the", "the hsp90:cdc37", "hsp90:cdc37 chaperone:co", "chaperone:co chaperone", "chaperone complex", "complex has", "tested but", "but is", "assumed to", "to occur", "occur similarly", "similarly to", "to the", "type erbb2.
              signaling", "erbb2.
              signaling by", "mutants has", "been organized", "organized into", "into subpathways", "subpathways based", "based on", "on the", "the current", "current knowledge", "knowledge of", "of biology", "biology of", "of these", "these mutants", "downstream signaling", "drug interaction", "and on", "the sequence", "sequence similarity", "similarity of", "of their", "their mutations.", "mutations in the", "in the kinase", "the kinase domain", "domain kd", "kd of", "of erbb2 result", "erbb2 result in", "result in constitutive", "in constitutive activation", "constitutive activation of", "activation of erbb2", "of erbb2 signaling", "signaling facilitate", "facilitate heterodimerization of", "heterodimerization of erbb2", "of erbb2 with", "erbb2 with other", "with other egfr", "other egfr family", "egfr family members", "family members and", "members and increase", "and increase the", "increase the signaling", "the signaling intensity", "intensity leading", "leading to cellular", "to cellular transformation", "transformation kancha", "kancha et al.", "et al. 2011", "al. 2011 .
              only", "2011 .
              only a", ".
              only a subset", "a subset of", "subset of potential", "of potential heterodimerization", "potential heterodimerization partners", "heterodimerization partners has", "partners has been", "has been tested", "been tested for", "tested for most", "for most erbb2", "most erbb2 kd", "erbb2 kd mutant", "kd mutant proteins", "proteins so", "so our annotations", "our annotations here", "annotations here are", "here are correspondingly", "are correspondingly limited.", "correspondingly limited. erbb2", "limited. erbb2 l755s", "erbb2 l755s and", "l755s and erbb2", "and erbb2 v777l", "erbb2 v777l cancer", "v777l cancer variants", "cancer variants were", "variants were shown", "were shown to", "shown to heterodimerize", "to heterodimerize with", "heterodimerize with erbb3", "erbb3 her3", "her3 at", "at a higher", "a higher rate", "higher rate than", "rate than wild", "than wild type", "wild type erbb2", "erbb2 croessmann", "croessmann et al.", "et al. 2019", "al. 2019 .", "2019 . increased", ". increased activity", "increased activity of", "activity of erbb2", "of erbb2 l755s", "l755s erbb2", "l755p erbb2", "v777l erbb2", "d769h erbb2", "d769y erbb2", "v842i erbb2", "erbb2 r896c and", "r896c and erbb2", "and erbb2 g778_p780dup", "erbb2 g778_p780dup in", "g778_p780dup in the", "in the presence", "the presence of", "presence of either", "of either egfr", "egfr kancha", "2011 bose", "bose et al.", "et al. 2013", "2013 or", "erbb3 kancha", "2013 collier", "collier et al.", "2013 as", "as a heterodimerization", "a heterodimerization partner", "heterodimerization partner was", "partner was also", "was also observed.", "also observed. the", "observed. the interplay", "the interplay of", "interplay of erbb2", "of erbb2 g778_p780dup", "g778_p780dup erbb2", "erbb2 i767m and", "i767m and erbb2", "and erbb2 r896c", "erbb2 r896c with", "r896c with erbb3", "with erbb3 has", "erbb3 has not", "has not been", "not been tested.", "been tested. erbb2", "tested. erbb2 l869r", "erbb2 l869r mutant", "l869r mutant shows", "mutant shows increased", "shows increased activity", "increased activity in", "activity in the", "presence of erbb3", "erbb3 which", "which is further", "is further augmented", "further augmented in", "augmented in the", "presence of dimerization", "of dimerization facilitating", "dimerization facilitating erbb3", "facilitating erbb3 e928g", "erbb3 e928g mutants", "mutants hanker", "hanker et al.", "et al. 2017", "al. 2017 .", "2017 . the", ". the interplay", "of erbb2 l869r", "erbb2 l869r with", "l869r with egfr", "with egfr has", "egfr has not", "been tested. heterodimerization", "tested. heterodimerization of", "of erbb2 kd", "kd mutants with", "mutants with erbb4", "with erbb4 has", "erbb4 has not", "not been tested", "been tested and", "tested and erbb4", "and erbb4 is", "erbb4 is a", "is a candidate", "a candidate heterodimerization", "candidate heterodimerization partner", "heterodimerization partner for", "partner for these", "for these kd", "these kd variants.
              erbb2", "kd variants.
              erbb2 h878y", "variants.
              erbb2 h878y mutant", "h878y mutant has", "mutant has ten", "has ten times", "ten times higher", "times higher kinase", "higher kinase activity", "kinase activity than", "activity than the", "than the wild", "the wild type", "erbb2 hu", "hu wan", "wan et al.", "et al. 2015", "2015 hu", "hu hu", "hu et al.", "but its heterodimerization", "its heterodimerization properties", "heterodimerization properties have", "properties have not", "have not been", "not been studied", "been studied and", "studied and it", "and it is", "it is therefore", "is therefore annotated", "therefore annotated as", "annotated as a", "as a candidate.
              ", "a candidate.
              ligand", "candidate.
              ligand requirements", "ligand requirements have", "requirements have not", "been studied in", "studied in the", "in the context", "the context of", "context of heterodimerization", "of heterodimerization of", "mutants but", "but it is", "it is assumed", "is assumed that", "assumed that ligands", "that ligands are", "ligands are required.
              ", "are required.
              the", "required.
              the signaling", "the signaling properties", "signaling properties of", "properties of erbb2", "of erbb2 l755m", "l755m gonzalez", "gonzalez alonso et", "alonso et al.", "l755w cosmic", "cosmic database: forbes", "database: forbes et", "forbes et al.", "v777e dietz", "dietz et al.", "v777m lee", "lee et al.", "et al. 2006", "2006 ross", "ross et al.", "et al. 2016", "2016 zehir", "zehir et al.", "d769n tschui", "tschui et al.", "v842e siroy", "siroy et al.", "r896h cancer", "cancer genome atlas", "genome atlas research", "atlas research network", "research network 2011", "l869q lee", "2006 and", "and erbb2 h878r", "h878r trowe", "trowe et al.", "et al. 2008", "2008 zehir", "2017 have", "not been experimentally", "been experimentally tested", "but they are", "they are predicted", "are predicted to", "predicted to be", "to be pathogenic", "pathogenic cosmic", "2017 and", "and they are", "they are annotated", "are annotated as", "annotated as candidates.", "as candidates. erbb2", "candidates. erbb2 t733i", "t733i trowe", "t798i trowe", "2008 hanker", "and erbb2 t798m", "t798m hanker", "2017 usually", "usually occur as", "occur as secondary", "as secondary erbb2", "secondary erbb2 mutations", "erbb2 mutations and", "mutations and are", "and are responsible", "are responsible for", "responsible for treatment", "for treatment failure.", "treatment failure. on", "failure. on their", "on their own", "own erbb2", "erbb2 t733i and", "t733i and erbb2", "and erbb2 t798i", "erbb2 t798i appear", "t798i appear to", "appear to be", "to be weakly", "be weakly transforming", "weakly transforming compared", "transforming compared with", "compared with the", "with the other", "the other erbb2", "other erbb2 kd", "erbb2 kd mutants.", "kd mutants. as", "mutants. as their", "as their signaling", "their signaling properties", "signaling properties have", "properties have been", "have been poorly", "been poorly studied", "studied erbb2", "t733i erbb2", "erbb2 t798i and", "t798i and erbb2", "erbb2 t798m are", "t798m are annotated", "annotated as candidates.
              the", "as candidates.
              the binding", "candidates.
              the binding of", "binding of erbb2", "kd mutants to", "mutants to erbin", "to erbin and", "erbin and the", "and the hsp90:cdc37", "the hsp90:cdc37 chaperone:co", "hsp90:cdc37 chaperone:co chaperone", "chaperone:co chaperone complex", "chaperone complex has", "complex has not", "been tested but", "tested but is", "but is assumed", "is assumed to", "assumed to occur", "to occur similarly", "occur similarly to", "similarly to the", "to the wild", "wild type erbb2.
              signaling", "type erbb2.
              signaling by", "erbb2.
              signaling by erbb2", "kd mutants has", "mutants has been", "has been organized", "been organized into", "organized into subpathways", "into subpathways based", "subpathways based on", "based on the", "on the current", "the current knowledge", "current knowledge of", "knowledge of biology", "of biology of", "biology of these", "of these mutants", "mutants heterodimerization", "heterodimerization downstream", "signaling drug", "interaction and", "and on the", "on the sequence", "the sequence similarity", "sequence similarity of", "similarity of their", "of their mutations.", "mutations in the kinase", "in the kinase domain", "kinase domain kd", "kd of erbb2", "of erbb2 result in", "erbb2 result in constitutive", "result in constitutive activation", "in constitutive activation of", "constitutive activation of erbb2", "activation of erbb2 signaling", "erbb2 signaling facilitate", "signaling facilitate heterodimerization", "facilitate heterodimerization of erbb2", "heterodimerization of erbb2 with", "of erbb2 with other", "erbb2 with other egfr", "with other egfr family", "other egfr family members", "egfr family members and", "family members and increase", "members and increase the", "and increase the signaling", "increase the signaling intensity", "signaling intensity leading", "intensity leading to", "leading to cellular transformation", "cellular transformation kancha", "transformation kancha et", "kancha et al. 2011", "et al. 2011 .
              only", "al. 2011 .
              only a", "2011 .
              only a subset", ".
              only a subset of", "a subset of potential", "subset of potential heterodimerization", "of potential heterodimerization partners", "potential heterodimerization partners has", "heterodimerization partners has been", "partners has been tested", "has been tested for", "been tested for most", "tested for most erbb2", "for most erbb2 kd", "most erbb2 kd mutant", "erbb2 kd mutant proteins", "mutant proteins so", "proteins so our", "so our annotations here", "our annotations here are", "annotations here are correspondingly", "here are correspondingly limited.", "are correspondingly limited. erbb2", "correspondingly limited. erbb2 l755s", "limited. erbb2 l755s and", "erbb2 l755s and erbb2", "l755s and erbb2 v777l", "and erbb2 v777l cancer", "erbb2 v777l cancer variants", "v777l cancer variants were", "cancer variants were shown", "variants were shown to", "were shown to heterodimerize", "shown to heterodimerize with", "to heterodimerize with erbb3", "with erbb3 her3", "her3 at a", "at a higher rate", "a higher rate than", "higher rate than wild", "rate than wild type", "than wild type erbb2", "type erbb2 croessmann", "erbb2 croessmann et", "croessmann et al. 2019", "et al. 2019 .", "al. 2019 . increased", "2019 . increased activity", ". increased activity of", "increased activity of erbb2", "activity of erbb2 l755s", "erbb2 l755s erbb2", "l755s erbb2 l755p", "erbb2 l755p erbb2", "l755p erbb2 v777l", "erbb2 v777l erbb2", "v777l erbb2 d769h", "erbb2 d769h erbb2", "d769h erbb2 d769y", "erbb2 d769y erbb2", "d769y erbb2 v842i", "erbb2 v842i erbb2", "v842i erbb2 r896c", "erbb2 r896c and erbb2", "r896c and erbb2 g778_p780dup", "and erbb2 g778_p780dup in", "erbb2 g778_p780dup in the", "g778_p780dup in the presence", "in the presence of", "the presence of either", "presence of either egfr", "either egfr kancha", "egfr kancha et", "al. 2011 bose", "2011 bose et", "bose et al. 2013", "al. 2013 or", "2013 or erbb3", "or erbb3 kancha", "erbb3 kancha et", "al. 2013 collier", "2013 collier et", "collier et al. 2013", "al. 2013 as", "2013 as a", "as a heterodimerization partner", "a heterodimerization partner was", "heterodimerization partner was also", "partner was also observed.", "was also observed. the", "also observed. the interplay", "observed. the interplay of", "the interplay of erbb2", "interplay of erbb2 g778_p780dup", "erbb2 g778_p780dup erbb2", "g778_p780dup erbb2 i767m", "erbb2 i767m and erbb2", "i767m and erbb2 r896c", "and erbb2 r896c with", "erbb2 r896c with erbb3", "r896c with erbb3 has", "with erbb3 has not", "erbb3 has not been", "has not been tested.", "not been tested. erbb2", "been tested. erbb2 l869r", "tested. erbb2 l869r mutant", "erbb2 l869r mutant shows", "l869r mutant shows increased", "mutant shows increased activity", "shows increased activity in", "increased activity in the", "activity in the presence", "the presence of erbb3", "of erbb3 which", "erbb3 which is", "which is further augmented", "is further augmented in", "further augmented in the", "augmented in the presence", "the presence of dimerization", "presence of dimerization facilitating", "of dimerization facilitating erbb3", "dimerization facilitating erbb3 e928g", "facilitating erbb3 e928g mutants", "e928g mutants hanker", "mutants hanker et", "hanker et al. 2017", "et al. 2017 .", "al. 2017 . the", "2017 . the interplay", ". the interplay of", "interplay of erbb2 l869r", "of erbb2 l869r with", "erbb2 l869r with egfr", "l869r with egfr has", "with egfr has not", "egfr has not been", "not been tested. heterodimerization", "been tested. heterodimerization of", "tested. heterodimerization of erbb2", "heterodimerization of erbb2 kd", "of erbb2 kd mutants", "erbb2 kd mutants with", "kd mutants with erbb4", "mutants with erbb4 has", "with erbb4 has not", "erbb4 has not been", "has not been tested", "not been tested and", "been tested and erbb4", "tested and erbb4 is", "and erbb4 is a", "erbb4 is a candidate", "is a candidate heterodimerization", "a candidate heterodimerization partner", "candidate heterodimerization partner for", "heterodimerization partner for these", "partner for these kd", "for these kd variants.
              erbb2", "these kd variants.
              erbb2 h878y", "kd variants.
              erbb2 h878y mutant", "variants.
              erbb2 h878y mutant has", "h878y mutant has ten", "mutant has ten times", "has ten times higher", "ten times higher kinase", "times higher kinase activity", "higher kinase activity than", "kinase activity than the", "activity than the wild", "than the wild type", "the wild type erbb2", "type erbb2 hu", "hu wan et", "wan et al. 2015", "al. 2015 hu", "hu hu et", "hu et al. 2015", "2015 but", "but its heterodimerization properties", "its heterodimerization properties have", "heterodimerization properties have not", "properties have not been", "have not been studied", "not been studied and", "been studied and it", "studied and it is", "and it is therefore", "it is therefore annotated", "is therefore annotated as", "therefore annotated as a", "annotated as a candidate.
              ", "as a candidate.
              ligand", "a candidate.
              ligand requirements", "candidate.
              ligand requirements have", "ligand requirements have not", "requirements have not been", "not been studied in", "been studied in the", "studied in the context", "in the context of", "the context of heterodimerization", "context of heterodimerization of", "of heterodimerization of erbb2", "kd mutants but", "mutants but it", "but it is assumed", "it is assumed that", "is assumed that ligands", "assumed that ligands are", "that ligands are required.
              ", "ligands are required.
              the", "are required.
              the signaling", "required.
              the signaling properties", "the signaling properties of", "signaling properties of erbb2", "properties of erbb2 l755m", "erbb2 l755m gonzalez", "l755m gonzalez alonso", "gonzalez alonso et al.", "alonso et al. 2015", "2015 erbb2", "erbb2 l755w cosmic", "l755w cosmic database:", "cosmic database: forbes et", "database: forbes et al.", "forbes et al. 2017", "2017 erbb2", "erbb2 v777e dietz", "v777e dietz et", "dietz et al. 2017", "erbb2 v777m lee", "v777m lee et", "lee et al. 2006", "al. 2006 ross", "2006 ross et", "ross et al. 2016", "al. 2016 zehir", "2016 zehir et", "zehir et al. 2017", "erbb2 d769n tschui", "d769n tschui et", "tschui et al. 2015", "erbb2 v842e siroy", "v842e siroy et", "siroy et al. 2015", "erbb2 r896h cancer", "r896h cancer genome", "cancer genome atlas research", "genome atlas research network", "atlas research network 2011", "2011 erbb2", "erbb2 l869q lee", "l869q lee et", "al. 2006 and", "2006 and erbb2", "erbb2 h878r trowe", "h878r trowe et", "trowe et al. 2008", "al. 2008 zehir", "2008 zehir et", "al. 2017 have", "2017 have not", "have not been experimentally", "not been experimentally tested", "experimentally tested but", "tested but they", "but they are predicted", "they are predicted to", "are predicted to be", "predicted to be pathogenic", "be pathogenic cosmic", "pathogenic cosmic database:", "al. 2017 and", "2017 and they", "and they are annotated", "they are annotated as", "are annotated as candidates.", "annotated as candidates. erbb2", "as candidates. erbb2 t733i", "erbb2 t733i trowe", "t733i trowe et", "2008 erbb2", "erbb2 t798i trowe", "t798i trowe et", "al. 2008 hanker", "2008 hanker et", "2017 and erbb2", "erbb2 t798m hanker", "t798m hanker et", "al. 2017 usually", "2017 usually occur", "usually occur as secondary", "occur as secondary erbb2", "as secondary erbb2 mutations", "secondary erbb2 mutations and", "erbb2 mutations and are", "mutations and are responsible", "and are responsible for", "are responsible for treatment", "responsible for treatment failure.", "for treatment failure. on", "treatment failure. on their", "failure. on their own", "their own erbb2", "own erbb2 t733i", "erbb2 t733i and erbb2", "t733i and erbb2 t798i", "and erbb2 t798i appear", "erbb2 t798i appear to", "t798i appear to be", "appear to be weakly", "to be weakly transforming", "be weakly transforming compared", "weakly transforming compared with", "transforming compared with the", "compared with the other", "with the other erbb2", "the other erbb2 kd", "other erbb2 kd mutants.", "erbb2 kd mutants. as", "kd mutants. as their", "mutants. as their signaling", "as their signaling properties", "their signaling properties have", "signaling properties have been", "properties have been poorly", "have been poorly studied", "poorly studied erbb2", "studied erbb2 t733i", "erbb2 t733i erbb2", "t733i erbb2 t798i", "erbb2 t798i and erbb2", "t798i and erbb2 t798m", "and erbb2 t798m are", "erbb2 t798m are annotated", "t798m are annotated as", "are annotated as candidates.
              the", "annotated as candidates.
              the binding", "as candidates.
              the binding of", "candidates.
              the binding of erbb2", "binding of erbb2 kd", "erbb2 kd mutants to", "kd mutants to erbin", "mutants to erbin and", "to erbin and the", "erbin and the hsp90:cdc37", "and the hsp90:cdc37 chaperone:co", "the hsp90:cdc37 chaperone:co chaperone", "hsp90:cdc37 chaperone:co chaperone complex", "chaperone:co chaperone complex has", "chaperone complex has not", "complex has not been", "not been tested but", "been tested but is", "tested but is assumed", "but is assumed to", "is assumed to occur", "assumed to occur similarly", "to occur similarly to", "occur similarly to the", "similarly to the wild", "to the wild type", "the wild type erbb2.
              signaling", "wild type erbb2.
              signaling by", "type erbb2.
              signaling by erbb2", "erbb2.
              signaling by erbb2 kd", "erbb2 kd mutants has", "kd mutants has been", "mutants has been organized", "has been organized into", "been organized into subpathways", "organized into subpathways based", "into subpathways based on", "subpathways based on the", "based on the current", "on the current knowledge", "the current knowledge of", "current knowledge of biology", "knowledge of biology of", "of biology of these", "biology of these mutants", "these mutants heterodimerization", "heterodimerization downstream signaling", "downstream signaling drug", "signaling drug interaction", "drug interaction and", "interaction and on", "and on the sequence", "on the sequence similarity", "the sequence similarity of", "sequence similarity of their", "similarity of their mutations.", "mutations in the kinase domain", "the kinase domain kd", "domain kd of", "kd of erbb2 result", "of erbb2 result in constitutive", "erbb2 result in constitutive activation", "result in constitutive activation of", "in constitutive activation of erbb2", "constitutive activation of erbb2 signaling", "of erbb2 signaling facilitate", "erbb2 signaling facilitate heterodimerization", "signaling facilitate heterodimerization of", "facilitate heterodimerization of erbb2 with", "heterodimerization of erbb2 with other", "of erbb2 with other egfr", "erbb2 with other egfr family", "with other egfr family members", "other egfr family members and", "egfr family members and increase", "family members and increase the", "members and increase the signaling", "and increase the signaling intensity", "the signaling intensity leading", "signaling intensity leading to", "intensity leading to cellular", "to cellular transformation kancha", "cellular transformation kancha et", "transformation kancha et al.", "kancha et al. 2011 .
              only", "et al. 2011 .
              only a", "al. 2011 .
              only a subset", "2011 .
              only a subset of", ".
              only a subset of potential", "a subset of potential heterodimerization", "subset of potential heterodimerization partners", "of potential heterodimerization partners has", "potential heterodimerization partners has been", "heterodimerization partners has been tested", "partners has been tested for", "has been tested for most", "been tested for most erbb2", "tested for most erbb2 kd", "for most erbb2 kd mutant", "most erbb2 kd mutant proteins", "kd mutant proteins so", "mutant proteins so our", "proteins so our annotations", "so our annotations here are", "our annotations here are correspondingly", "annotations here are correspondingly limited.", "here are correspondingly limited. erbb2", "are correspondingly limited. erbb2 l755s", "correspondingly limited. erbb2 l755s and", "limited. erbb2 l755s and erbb2", "erbb2 l755s and erbb2 v777l", "l755s and erbb2 v777l cancer", "and erbb2 v777l cancer variants", "erbb2 v777l cancer variants were", "v777l cancer variants were shown", "cancer variants were shown to", "variants were shown to heterodimerize", "were shown to heterodimerize with", "shown to heterodimerize with erbb3", "heterodimerize with erbb3 her3", "erbb3 her3 at", "her3 at a higher", "at a higher rate than", "a higher rate than wild", "higher rate than wild type", "rate than wild type erbb2", "wild type erbb2 croessmann", "type erbb2 croessmann et", "erbb2 croessmann et al.", "croessmann et al. 2019 .", "et al. 2019 . increased", "al. 2019 . increased activity", "2019 . increased activity of", ". increased activity of erbb2", "increased activity of erbb2 l755s", "of erbb2 l755s erbb2", "erbb2 l755s erbb2 l755p", "erbb2 l755p erbb2 v777l", "erbb2 v777l erbb2 d769h", "erbb2 d769h erbb2 d769y", "erbb2 d769y erbb2 v842i", "erbb2 v842i erbb2 r896c", "v842i erbb2 r896c and", "erbb2 r896c and erbb2 g778_p780dup", "r896c and erbb2 g778_p780dup in", "and erbb2 g778_p780dup in the", "erbb2 g778_p780dup in the presence", "g778_p780dup in the presence of", "in the presence of either", "the presence of either egfr", "of either egfr kancha", "either egfr kancha et", "egfr kancha et al.", "et al. 2011 bose", "al. 2011 bose et", "2011 bose et al.", "et al. 2013 or", "al. 2013 or erbb3", "or erbb3 kancha et", "erbb3 kancha et al.", "et al. 2013 collier", "al. 2013 collier et", "2013 collier et al.", "et al. 2013 as", "al. 2013 as a", "2013 as a heterodimerization", "as a heterodimerization partner was", "a heterodimerization partner was also", "heterodimerization partner was also observed.", "partner was also observed. the", "was also observed. the interplay", "also observed. the interplay of", "observed. the interplay of erbb2", "the interplay of erbb2 g778_p780dup", "of erbb2 g778_p780dup erbb2", "erbb2 g778_p780dup erbb2 i767m", "g778_p780dup erbb2 i767m and", "erbb2 i767m and erbb2 r896c", "i767m and erbb2 r896c with", "and erbb2 r896c with erbb3", "erbb2 r896c with erbb3 has", "r896c with erbb3 has not", "with erbb3 has not been", "erbb3 has not been tested.", "has not been tested. erbb2", "not been tested. erbb2 l869r", "been tested. erbb2 l869r mutant", "tested. erbb2 l869r mutant shows", "erbb2 l869r mutant shows increased", "l869r mutant shows increased activity", "mutant shows increased activity in", "shows increased activity in the", "increased activity in the presence", "activity in the presence of", "in the presence of erbb3", "presence of erbb3 which", "of erbb3 which is", "erbb3 which is further", "which is further augmented in", "is further augmented in the", "further augmented in the presence", "augmented in the presence of", "in the presence of dimerization", "the presence of dimerization facilitating", "presence of dimerization facilitating erbb3", "of dimerization facilitating erbb3 e928g", "dimerization facilitating erbb3 e928g mutants", "erbb3 e928g mutants hanker", "e928g mutants hanker et", "mutants hanker et al.", "hanker et al. 2017 .", "et al. 2017 . the", "al. 2017 . the interplay", "2017 . the interplay of", ". the interplay of erbb2", "the interplay of erbb2 l869r", "interplay of erbb2 l869r with", "of erbb2 l869r with egfr", "erbb2 l869r with egfr has", "l869r with egfr has not", "with egfr has not been", "egfr has not been tested.", "has not been tested. heterodimerization", "not been tested. heterodimerization of", "been tested. heterodimerization of erbb2", "tested. heterodimerization of erbb2 kd", "heterodimerization of erbb2 kd mutants", "of erbb2 kd mutants with", "erbb2 kd mutants with erbb4", "kd mutants with erbb4 has", "mutants with erbb4 has not", "with erbb4 has not been", "erbb4 has not been tested", "has not been tested and", "not been tested and erbb4", "been tested and erbb4 is", "tested and erbb4 is a", "and erbb4 is a candidate", "erbb4 is a candidate heterodimerization", "is a candidate heterodimerization partner", "a candidate heterodimerization partner for", "candidate heterodimerization partner for these", "heterodimerization partner for these kd", "partner for these kd variants.
              erbb2", "for these kd variants.
              erbb2 h878y", "these kd variants.
              erbb2 h878y mutant", "kd variants.
              erbb2 h878y mutant has", "variants.
              erbb2 h878y mutant has ten", "h878y mutant has ten times", "mutant has ten times higher", "has ten times higher kinase", "ten times higher kinase activity", "times higher kinase activity than", "higher kinase activity than the", "kinase activity than the wild", "activity than the wild type", "than the wild type erbb2", "wild type erbb2 hu", "erbb2 hu wan", "hu wan et al.", "et al. 2015 hu", "2015 hu hu", "hu hu et al.", "al. 2015 but", "2015 but its", "but its heterodimerization properties have", "its heterodimerization properties have not", "heterodimerization properties have not been", "properties have not been studied", "have not been studied and", "not been studied and it", "been studied and it is", "studied and it is therefore", "and it is therefore annotated", "it is therefore annotated as", "is therefore annotated as a", "therefore annotated as a candidate.
              ", "annotated as a candidate.
              ligand", "as a candidate.
              ligand requirements", "a candidate.
              ligand requirements have", "candidate.
              ligand requirements have not", "ligand requirements have not been", "requirements have not been studied", "have not been studied in", "not been studied in the", "been studied in the context", "studied in the context of", "in the context of heterodimerization", "the context of heterodimerization of", "context of heterodimerization of erbb2", "of heterodimerization of erbb2 kd", "erbb2 kd mutants but", "kd mutants but it", "mutants but it is", "but it is assumed that", "it is assumed that ligands", "is assumed that ligands are", "assumed that ligands are required.
              ", "that ligands are required.
              the", "ligands are required.
              the signaling", "are required.
              the signaling properties", "required.
              the signaling properties of", "the signaling properties of erbb2", "signaling properties of erbb2 l755m", "of erbb2 l755m gonzalez", "erbb2 l755m gonzalez alonso", "l755m gonzalez alonso et", "gonzalez alonso et al. 2015", "al. 2015 erbb2", "2015 erbb2 l755w", "erbb2 l755w cosmic database:", "l755w cosmic database: forbes", "cosmic database: forbes et al.", "database: forbes et al. 2017", "al. 2017 erbb2", "2017 erbb2 v777e", "erbb2 v777e dietz et", "v777e dietz et al.", "2017 erbb2 v777m", "erbb2 v777m lee et", "v777m lee et al.", "et al. 2006 ross", "al. 2006 ross et", "2006 ross et al.", "et al. 2016 zehir", "al. 2016 zehir et", "2016 zehir et al.", "2017 erbb2 d769n", "erbb2 d769n tschui et", "d769n tschui et al.", "2015 erbb2 v842e", "erbb2 v842e siroy et", "v842e siroy et al.", "2015 erbb2 r896h", "erbb2 r896h cancer genome", "r896h cancer genome atlas", "cancer genome atlas research network", "genome atlas research network 2011", "network 2011 erbb2", "2011 erbb2 l869q", "erbb2 l869q lee et", "l869q lee et al.", "et al. 2006 and", "al. 2006 and erbb2", "2006 and erbb2 h878r", "and erbb2 h878r trowe", "erbb2 h878r trowe et", "h878r trowe et al.", "et al. 2008 zehir", "al. 2008 zehir et", "2008 zehir et al.", "et al. 2017 have", "al. 2017 have not", "2017 have not been", "have not been experimentally tested", "been experimentally tested but", "experimentally tested but they", "tested but they are", "but they are predicted to", "they are predicted to be", "are predicted to be pathogenic", "to be pathogenic cosmic", "be pathogenic cosmic database:", "pathogenic cosmic database: forbes", "et al. 2017 and", "al. 2017 and they", "2017 and they are", "and they are annotated as", "they are annotated as candidates.", "are annotated as candidates. erbb2", "annotated as candidates. erbb2 t733i", "candidates. erbb2 t733i trowe", "erbb2 t733i trowe et", "t733i trowe et al.", "al. 2008 erbb2", "2008 erbb2 t798i", "erbb2 t798i trowe et", "t798i trowe et al.", "et al. 2008 hanker", "al. 2008 hanker et", "2008 hanker et al.", "al. 2017 and erbb2", "2017 and erbb2 t798m", "and erbb2 t798m hanker", "erbb2 t798m hanker et", "t798m hanker et al.", "et al. 2017 usually", "al. 2017 usually occur", "2017 usually occur as", "usually occur as secondary erbb2", "occur as secondary erbb2 mutations", "as secondary erbb2 mutations and", "secondary erbb2 mutations and are", "erbb2 mutations and are responsible", "mutations and are responsible for", "and are responsible for treatment", "are responsible for treatment failure.", "responsible for treatment failure. on", "for treatment failure. on their", "treatment failure. on their own", "on their own erbb2", "their own erbb2 t733i", "own erbb2 t733i and", "erbb2 t733i and erbb2 t798i", "t733i and erbb2 t798i appear", "and erbb2 t798i appear to", "erbb2 t798i appear to be", "t798i appear to be weakly", "appear to be weakly transforming", "to be weakly transforming compared", "be weakly transforming compared with", "weakly transforming compared with the", "transforming compared with the other", "compared with the other erbb2", "with the other erbb2 kd", "the other erbb2 kd mutants.", "other erbb2 kd mutants. as", "erbb2 kd mutants. as their", "kd mutants. as their signaling", "mutants. as their signaling properties", "as their signaling properties have", "their signaling properties have been", "signaling properties have been poorly", "properties have been poorly studied", "been poorly studied erbb2", "poorly studied erbb2 t733i", "erbb2 t733i erbb2 t798i", "t733i erbb2 t798i and", "erbb2 t798i and erbb2 t798m", "t798i and erbb2 t798m are", "and erbb2 t798m are annotated", "erbb2 t798m are annotated as", "t798m are annotated as candidates.
              the", "are annotated as candidates.
              the binding", "annotated as candidates.
              the binding of", "as candidates.
              the binding of erbb2", "candidates.
              the binding of erbb2 kd", "binding of erbb2 kd mutants", "of erbb2 kd mutants to", "erbb2 kd mutants to erbin", "kd mutants to erbin and", "mutants to erbin and the", "to erbin and the hsp90:cdc37", "erbin and the hsp90:cdc37 chaperone:co", "and the hsp90:cdc37 chaperone:co chaperone", "the hsp90:cdc37 chaperone:co chaperone complex", "hsp90:cdc37 chaperone:co chaperone complex has", "chaperone:co chaperone complex has not", "chaperone complex has not been", "complex has not been tested", "has not been tested but", "not been tested but is", "been tested but is assumed", "tested but is assumed to", "but is assumed to occur", "is assumed to occur similarly", "assumed to occur similarly to", "to occur similarly to the", "occur similarly to the wild", "similarly to the wild type", "to the wild type erbb2.
              signaling", "the wild type erbb2.
              signaling by", "wild type erbb2.
              signaling by erbb2", "type erbb2.
              signaling by erbb2 kd", "erbb2.
              signaling by erbb2 kd mutants", "by erbb2 kd mutants has", "erbb2 kd mutants has been", "kd mutants has been organized", "mutants has been organized into", "has been organized into subpathways", "been organized into subpathways based", "organized into subpathways based on", "into subpathways based on the", "subpathways based on the current", "based on the current knowledge", "on the current knowledge of", "the current knowledge of biology", "current knowledge of biology of", "knowledge of biology of these", "of biology of these mutants", "of these mutants heterodimerization", "mutants heterodimerization downstream", "downstream signaling drug interaction", "drug interaction and on", "interaction and on the", "and on the sequence similarity", "on the sequence similarity of", "the sequence similarity of their", "sequence similarity of their mutations." ] }, { "record_id": "GLY_000594_1_1898", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "201556", "r hsa", "hsa 201556", "r hsa 201556" ] }, { "record_id": "GLY_000594_1_1898", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by alk", "signaling by alk", "the anaplastic", "anaplastic lymphoma", "lymphoma kinase", "is a", "a transmembrane", "transmembrane receptor", "receptor tyrosine", "tyrosine kinase", "kinase that", "along with", "with related", "related receptor", "receptor ltk", "leukocyte tyrosine", "kinase receptor", "a member", "member of", "of the", "the insulin", "insulin receptor", "receptor superfamily", "iwahara et", "et al", "1997 .", ". alk", "alk was", "was discovered", "discovered as", "as an", "an oncogene", "oncogene in", "in anaplastic", "anaplastic large", "large cell", "cell lymphomas", "but also", "also plays", "plays an", "an oncogenic", "oncogenic role", "role in", "in other", "other cancer", "cancer types", "such as", "as non", "non small", "small cell", "cell lung", "lung cancer", "inflammatory myofibroblastic", "myofibroblastic tumours", "neuroblastoma and", "and glioblastoma.", "glioblastoma. in", "in cancer", "the chromosomal", "chromosomal region", "region encoding", "encoding alk", "alk frequently", "frequently undergoes", "undergoes genomic", "genomic rearrangements", "resulting in", "in the", "the formation", "formation of", "of alk", "alk fusion", "fusion proteins", "as npm\u2011alk", "the result", "result of", "of a", "a translocation", "translocation event", "t 2", "2 5", "p23 q35", "which is", "is predominant", "predominant in", "in alcl", "and eml4\u2011alk", "an inversion", "inversion event", "event on", "on chromosome", "chromosome 2", "morris et", "couts et", "2018 .", ". these", "these fusion", "proteins consist", "consist of", "the c\u2011terminal", "c\u2011terminal region", "region of", "encompassing the", "the kinase", "kinase domain", "domain and", "and the", "the effector", "effector protein", "protein binding", "binding domain", "with loss", "loss of", "the transmembrane", "transmembrane domain", "while the", "the n\u2011terminus", "n\u2011terminus of", "the fusion", "fusion protein", "protein contains", "contains the", "the dimerization", "dimerization domain", "domain of", "the partner", "partner gene.", "gene. fusion", "proteins of", "alk are", "are therefore", "therefore capable", "capable of", "of ligand\u2011independent", "ligand\u2011independent dimerization", "in constitutive", "constitutive alk", "alk signaling", "reviewed in", "in duyster", "duyster et", "chiarle et", "della corte", "corte et", "hallberg and", "and palmer", "janoueix larousey", "larousey et", "ducray et", "2019 .", ". additionally", "amplification of", "alk and/or", "and/or point", "point mutations", "mutations leading", "leading to", "to its", "its constitutive", "constitutive activation", "activation have", "have been", "been detected", "detected in", "in neuroblastoma", "in mcduff", "mcduff et", "2011 .", ".

              many", "

              many of", "the functional", "functional studies", "studies on", "on alk", "alk have", "been conducted", "conducted in", "the context", "context of", "of oncogenic", "oncogenic forms", "forms of", "the protein.", "protein. in", "in contrast", "fewer studies", "studies have", "conducted on", "on the", "the wild", "wild type", "type protein", "protein under", "under normal", "normal physiological", "physiological conditions", "and indeed", "was initially", "initially classed", "classed as", "an orphan", "orphan receptor", "receptor with", "with no", "no identified", "identified ligand.", "ligand. two", "two small", "small heparin", "heparin binding", "binding growth", "growth factors", "and midkine", "were initially", "initially identified", "identified as", "as potential", "potential ligands", "ligands however", "however subsequent", "subsequent studies", "studies failed", "failed to", "to support", "support this", "stoica et", "mathivet et", "moog lutz", "lutz et", "motegi et", "in wellstein", "wellstein et", "winkler et", "herradon and", "and perez", "perez garcia", "2014 .", ". more", "more recently", "alkal1 and", "and alkal2", "also known", "known as", "as fam150a", "fam150a and", "and fam150b", "been identified", "as ligands", "ligands for", "for both", "both alk", "alk and", "the related", "related ltk", "ltk receptor", "albeit with", "with differing", "differing potencies", "zhang et", "guan et", "reshetnyak et", "fadeev et", "de munck", "munck et", "borenas et", "in hallberg", "2016 .", ". whereas", "whereas ltk", "receptor is", "is potently", "potently activated", "activated by", "by both", "both alkal1", "alk is", "is only", "only weakly", "weakly stimulated", "stimulated by", "by alkal1", ". ligand", "ligand binding", "binding induces", "induces the", "dimerization of", "the receptor", "receptor and", "and transautophosphorylation", "in a", "a fully", "fully activated", "activated receptor", "receptor that", "that triggers", "triggers downstream", "downstream signaling", "signaling cascades", "cascades such", "as ras", "pi3k and", "and irs1", "irs1 signaling.", "signaling. alk", "alk may", "may also", "also undergo", "undergo ligand", "ligand independent", "independent activation", "activation through", "through rptpb/rptpz", "deuel et", "2013 .", ".

              alk", "

              alk is", "is mainly", "mainly expressed", "expressed in", "the developing", "developing central", "central and", "and peripheral", "peripheral nervous", "nervous system", "system and", "and plays", "plays a", "a role", "in differentiation", "differentiation during", "during development", "souttou et", "gouzi et", "degoutin et", "2007 .", ". in", "in drosophila", "drosophila and", "and mice", "a thinness", "thinness gene", "gene involved", "involved in", "the resistance", "resistance to", "to weight", "weight gain", "orthofer et", "2020 .", ". through", "through activation", "activation of", "of stat3", "stat3 targets", "alk also", "also appears", "appears to", "to play", "play a", "in response", "response to", "to ethanol", "hamada et", "2021 .", "the anaplastic lymphoma", "anaplastic lymphoma kinase", "kinase alk", "is a transmembrane", "a transmembrane receptor", "transmembrane receptor tyrosine", "receptor tyrosine kinase", "tyrosine kinase that", "that along", "along with related", "with related receptor", "related receptor ltk", "ltk leukocyte", "leukocyte tyrosine kinase", "tyrosine kinase receptor", "is a member", "a member of", "member of the", "of the insulin", "the insulin receptor", "insulin receptor superfamily", "superfamily iwahara", "iwahara et al", "al 1997", "1997 . alk", ". alk was", "alk was discovered", "was discovered as", "discovered as an", "as an oncogene", "an oncogene in", "oncogene in anaplastic", "in anaplastic large", "anaplastic large cell", "large cell lymphomas", "lymphomas alcls", "but also plays", "also plays an", "plays an oncogenic", "an oncogenic role", "oncogenic role in", "role in other", "in other cancer", "other cancer types", "types such", "such as non", "as non small", "non small cell", "small cell lung", "cell lung cancer", "cancer nsclc", "inflammatory myofibroblastic tumours", "tumours imt", "melanoma neuroblastoma", "neuroblastoma and glioblastoma.", "and glioblastoma. in", "glioblastoma. in cancer", "cancer the", "the chromosomal region", "chromosomal region encoding", "region encoding alk", "encoding alk frequently", "alk frequently undergoes", "frequently undergoes genomic", "undergoes genomic rearrangements", "rearrangements resulting", "resulting in the", "in the formation", "the formation of", "formation of alk", "of alk fusion", "alk fusion proteins", "proteins such", "such as npm\u2011alk", "npm\u2011alk the", "the result of", "result of a", "of a translocation", "a translocation event", "event t", "t 2 5", "5 p23", "q35 which", "which is predominant", "is predominant in", "predominant in alcl", "alcl and", "eml4\u2011alk an", "an inversion event", "inversion event on", "event on chromosome", "on chromosome 2", "morris et al", "al 1994", "1994 couts", "couts et al", "al 2018", "2018 . these", ". these fusion", "these fusion proteins", "fusion proteins consist", "proteins consist of", "consist of the", "of the c\u2011terminal", "the c\u2011terminal region", "c\u2011terminal region of", "region of alk", "alk encompassing", "encompassing the kinase", "the kinase domain", "kinase domain and", "domain and the", "and the effector", "the effector protein", "effector protein binding", "protein binding domain", "domain with", "with loss of", "loss of the", "of the transmembrane", "the transmembrane domain", "while the n\u2011terminus", "the n\u2011terminus of", "n\u2011terminus of the", "of the fusion", "the fusion protein", "fusion protein contains", "protein contains the", "contains the dimerization", "the dimerization domain", "dimerization domain of", "domain of the", "of the partner", "the partner gene.", "partner gene. fusion", "gene. fusion proteins", "fusion proteins of", "proteins of alk", "of alk are", "alk are therefore", "are therefore capable", "therefore capable of", "capable of ligand\u2011independent", "of ligand\u2011independent dimerization", "dimerization resulting", "resulting in constitutive", "in constitutive alk", "constitutive alk signaling", "signaling reviewed", "reviewed in duyster", "in duyster et", "duyster et al", "al 2001", "2001 chiarle", "chiarle et al", "al 2008", "2008 della", "della corte et", "corte et al", "2018 hallberg", "hallberg and palmer", "palmer 2013", "2013 hallberg", "palmer 2016", "2016 janoueix", "janoueix larousey et", "larousey et al", "2018 ducray", "ducray et al", "al 2019", "2019 . additionally", "additionally amplification", "amplification of alk", "of alk and/or", "alk and/or point", "and/or point mutations", "point mutations leading", "mutations leading to", "leading to its", "to its constitutive", "its constitutive activation", "constitutive activation have", "activation have been", "have been detected", "been detected in", "detected in neuroblastoma", "neuroblastoma reviewed", "reviewed in mcduff", "in mcduff et", "mcduff et al", "al 2011", "2011 .

              many", ".

              many of", "

              many of the", "of the functional", "the functional studies", "functional studies on", "studies on alk", "on alk have", "alk have been", "have been conducted", "been conducted in", "conducted in the", "in the context", "the context of", "context of oncogenic", "of oncogenic forms", "oncogenic forms of", "forms of the", "of the protein.", "the protein. in", "protein. in contrast", "contrast fewer", "fewer studies have", "studies have been", "been conducted on", "conducted on the", "on the wild", "the wild type", "wild type protein", "type protein under", "protein under normal", "under normal physiological", "normal physiological conditions", "conditions and", "indeed alk", "alk was initially", "was initially classed", "initially classed as", "classed as an", "as an orphan", "an orphan receptor", "orphan receptor with", "receptor with no", "with no identified", "no identified ligand.", "identified ligand. two", "ligand. two small", "two small heparin", "small heparin binding", "heparin binding growth", "binding growth factors", "factors pleiotrophin", "pleiotrophin ptn", "ptn and", "midkine mdk", "were initially identified", "initially identified as", "identified as potential", "as potential ligands", "potential ligands however", "ligands however subsequent", "however subsequent studies", "subsequent studies failed", "studies failed to", "failed to support", "to support this", "this stoica", "stoica et al", "2001 stoica", "al 2002", "2002 mathivet", "mathivet et al", "al 2007", "2007 moog", "moog lutz et", "lutz et al", "al 2005", "2005 motegi", "motegi et al", "al 2004", "2004 reviewed", "reviewed in wellstein", "in wellstein et", "wellstein et al", "al 2012", "2012 winkler", "winkler et al", "al 2014", "2014 herradon", "herradon and perez", "and perez garcia", "garcia 2014", "2014 . more", ". more recently", "recently alkal1", "alkal1 and alkal2", "alkal2 also", "also known as", "known as fam150a", "as fam150a and", "fam150a and fam150b", "fam150b have", "have been identified", "been identified as", "identified as ligands", "as ligands for", "ligands for both", "for both alk", "both alk and", "alk and the", "and the related", "the related ltk", "related ltk receptor", "receptor albeit", "albeit with differing", "with differing potencies", "potencies zhang", "zhang et al", "2014 guan", "guan et al", "al 2015", "2015 reshetnyak", "reshetnyak et al", "2018 fadeev", "fadeev et al", "2018 reshetnyak", "al 2021", "2021 de", "de munck et", "munck et al", "2021 borenas", "borenas et al", "2021 reviewed", "reviewed in hallberg", "in hallberg and", "2016 . whereas", ". whereas ltk", "whereas ltk receptor", "ltk receptor is", "receptor is potently", "is potently activated", "potently activated by", "activated by both", "by both alkal1", "both alkal1 and", "alkal2 alk", "alk is only", "is only weakly", "only weakly stimulated", "weakly stimulated by", "stimulated by alkal1", "alkal1 reshetnyak", "2018 . ligand", ". ligand binding", "ligand binding induces", "binding induces the", "induces the dimerization", "the dimerization of", "dimerization of the", "of the receptor", "the receptor and", "receptor and transautophosphorylation", "transautophosphorylation resulting", "resulting in a", "in a fully", "a fully activated", "fully activated receptor", "activated receptor that", "receptor that triggers", "that triggers downstream", "triggers downstream signaling", "downstream signaling cascades", "signaling cascades such", "cascades such as", "such as ras", "ras pi3k", "pi3k and irs1", "and irs1 signaling.", "irs1 signaling. alk", "signaling. alk may", "alk may also", "may also undergo", "also undergo ligand", "undergo ligand independent", "ligand independent activation", "independent activation through", "activation through rptpb/rptpz", "rptpb/rptpz deuel", "deuel et al", "al 2013", "2013 .

              alk", ".

              alk is", "

              alk is mainly", "is mainly expressed", "mainly expressed in", "expressed in the", "in the developing", "the developing central", "developing central and", "central and peripheral", "and peripheral nervous", "peripheral nervous system", "nervous system and", "system and plays", "and plays a", "plays a role", "a role in", "role in differentiation", "in differentiation during", "differentiation during development", "development souttou", "souttou et al", "2001 gouzi", "gouzi et al", "2005 degoutin", "degoutin et al", "2007 . in", ". in drosophila", "in drosophila and", "drosophila and mice", "mice alk", "alk is a", "is a thinness", "a thinness gene", "thinness gene involved", "gene involved in", "involved in the", "in the resistance", "the resistance to", "resistance to weight", "to weight gain", "gain orthofer", "orthofer et al", "al 2020", "2020 . through", ". through activation", "through activation of", "activation of stat3", "of stat3 targets", "targets alk", "alk also appears", "also appears to", "appears to play", "to play a", "play a role", "role in response", "in response to", "response to ethanol", "ethanol hamada", "hamada et al", "the anaplastic lymphoma kinase", "lymphoma kinase alk", "is a transmembrane receptor", "a transmembrane receptor tyrosine", "transmembrane receptor tyrosine kinase", "receptor tyrosine kinase that", "kinase that along", "that along with", "along with related receptor", "with related receptor ltk", "receptor ltk leukocyte", "ltk leukocyte tyrosine", "leukocyte tyrosine kinase receptor", "kinase receptor is", "receptor is a", "is a member of", "a member of the", "member of the insulin", "of the insulin receptor", "the insulin receptor superfamily", "receptor superfamily iwahara", "superfamily iwahara et", "et al 1997", "al 1997 .", "1997 . alk was", ". alk was discovered", "alk was discovered as", "was discovered as an", "discovered as an oncogene", "as an oncogene in", "an oncogene in anaplastic", "oncogene in anaplastic large", "in anaplastic large cell", "anaplastic large cell lymphomas", "cell lymphomas alcls", "alcls but", "but also plays an", "also plays an oncogenic", "plays an oncogenic role", "an oncogenic role in", "oncogenic role in other", "role in other cancer", "in other cancer types", "cancer types such", "types such as", "such as non small", "as non small cell", "non small cell lung", "small cell lung cancer", "lung cancer nsclc", "nsclc inflammatory", "myofibroblastic tumours imt", "imt melanoma", "melanoma neuroblastoma and", "neuroblastoma and glioblastoma. in", "and glioblastoma. in cancer", "in cancer the", "cancer the chromosomal", "the chromosomal region encoding", "chromosomal region encoding alk", "region encoding alk frequently", "encoding alk frequently undergoes", "alk frequently undergoes genomic", "frequently undergoes genomic rearrangements", "genomic rearrangements resulting", "rearrangements resulting in", "resulting in the formation", "in the formation of", "the formation of alk", "formation of alk fusion", "of alk fusion proteins", "fusion proteins such", "proteins such as", "as npm\u2011alk the", "npm\u2011alk the result", "the result of a", "result of a translocation", "of a translocation event", "translocation event t", "event t 2", "2 5 p23", "5 p23 q35", "p23 q35 which", "q35 which is", "which is predominant in", "is predominant in alcl", "in alcl and", "alcl and eml4\u2011alk", "and eml4\u2011alk an", "eml4\u2011alk an inversion", "an inversion event on", "inversion event on chromosome", "event on chromosome 2", "2 morris", "et al 1994", "1994 couts et", "et al 2018", "al 2018 .", "2018 . these fusion", ". these fusion proteins", "these fusion proteins consist", "fusion proteins consist of", "proteins consist of the", "consist of the c\u2011terminal", "of the c\u2011terminal region", "the c\u2011terminal region of", "c\u2011terminal region of alk", "of alk encompassing", "alk encompassing the", "encompassing the kinase domain", "the kinase domain and", "kinase domain and the", "domain and the effector", "and the effector protein", "the effector protein binding", "effector protein binding domain", "binding domain with", "domain with loss", "with loss of the", "loss of the transmembrane", "of the transmembrane domain", "domain while", "while the n\u2011terminus of", "the n\u2011terminus of the", "n\u2011terminus of the fusion", "of the fusion protein", "the fusion protein contains", "fusion protein contains the", "protein contains the dimerization", "contains the dimerization domain", "the dimerization domain of", "dimerization domain of the", "domain of the partner", "of the partner gene.", "the partner gene. fusion", "partner gene. fusion proteins", "gene. fusion proteins of", "fusion proteins of alk", "proteins of alk are", "of alk are therefore", "alk are therefore capable", "are therefore capable of", "therefore capable of ligand\u2011independent", "capable of ligand\u2011independent dimerization", "ligand\u2011independent dimerization resulting", "dimerization resulting in", "resulting in constitutive alk", "in constitutive alk signaling", "alk signaling reviewed", "signaling reviewed in", "reviewed in duyster et", "in duyster et al", "et al 2001", "2001 chiarle et", "et al 2008", "2008 della corte", "della corte et al", "2018 hallberg and", "and palmer 2013", "2013 hallberg and", "and palmer 2016", "2016 janoueix larousey", "janoueix larousey et al", "2018 ducray et", "et al 2019", "al 2019 .", ". additionally amplification", "additionally amplification of", "amplification of alk and/or", "of alk and/or point", "alk and/or point mutations", "and/or point mutations leading", "point mutations leading to", "mutations leading to its", "leading to its constitutive", "to its constitutive activation", "its constitutive activation have", "constitutive activation have been", "activation have been detected", "have been detected in", "been detected in neuroblastoma", "in neuroblastoma reviewed", "neuroblastoma reviewed in", "reviewed in mcduff et", "in mcduff et al", "et al 2011", "al 2011 .", "2011 .

              many of", ".

              many of the", "

              many of the functional", "of the functional studies", "the functional studies on", "functional studies on alk", "studies on alk have", "on alk have been", "alk have been conducted", "have been conducted in", "been conducted in the", "conducted in the context", "in the context of", "the context of oncogenic", "context of oncogenic forms", "of oncogenic forms of", "oncogenic forms of the", "forms of the protein.", "of the protein. in", "the protein. in contrast", "in contrast fewer", "contrast fewer studies", "fewer studies have been", "studies have been conducted", "have been conducted on", "been conducted on the", "conducted on the wild", "on the wild type", "the wild type protein", "wild type protein under", "type protein under normal", "protein under normal physiological", "under normal physiological conditions", "physiological conditions and", "conditions and indeed", "and indeed alk", "indeed alk was", "alk was initially classed", "was initially classed as", "initially classed as an", "classed as an orphan", "as an orphan receptor", "an orphan receptor with", "orphan receptor with no", "receptor with no identified", "with no identified ligand.", "no identified ligand. two", "identified ligand. two small", "ligand. two small heparin", "two small heparin binding", "small heparin binding growth", "heparin binding growth factors", "growth factors pleiotrophin", "ptn and midkine", "and midkine mdk", "mdk were", "were initially identified as", "initially identified as potential", "identified as potential ligands", "as potential ligands however", "potential ligands however subsequent", "ligands however subsequent studies", "however subsequent studies failed", "subsequent studies failed to", "studies failed to support", "failed to support this", "support this stoica", "this stoica et", "2001 stoica et", "et al 2002", "2002 mathivet et", "et al 2007", "2007 moog lutz", "moog lutz et al", "et al 2005", "2005 motegi et", "et al 2004", "2004 reviewed in", "reviewed in wellstein et", "in wellstein et al", "et al 2012", "2012 winkler et", "et al 2014", "2014 herradon and", "herradon and perez garcia", "perez garcia 2014", "garcia 2014 .", "2014 . more recently", "more recently alkal1", "recently alkal1 and", "and alkal2 also", "alkal2 also known", "also known as fam150a", "known as fam150a and", "as fam150a and fam150b", "and fam150b have", "fam150b have been", "have been identified as", "been identified as ligands", "identified as ligands for", "as ligands for both", "ligands for both alk", "for both alk and", "both alk and the", "alk and the related", "and the related ltk", "the related ltk receptor", "ltk receptor albeit", "receptor albeit with", "albeit with differing potencies", "differing potencies zhang", "potencies zhang et", "2014 guan et", "et al 2015", "2015 reshetnyak et", "2018 fadeev et", "2018 reshetnyak et", "et al 2021", "2021 de munck", "de munck et al", "2021 borenas et", "2021 reviewed in", "reviewed in hallberg and", "in hallberg and palmer", "palmer 2016 .", "2016 . whereas ltk", ". whereas ltk receptor", "whereas ltk receptor is", "ltk receptor is potently", "receptor is potently activated", "is potently activated by", "potently activated by both", "activated by both alkal1", "by both alkal1 and", "both alkal1 and alkal2", "and alkal2 alk", "alkal2 alk is", "alk is only weakly", "is only weakly stimulated", "only weakly stimulated by", "weakly stimulated by alkal1", "by alkal1 reshetnyak", "alkal1 reshetnyak et", "2018 . ligand binding", ". ligand binding induces", "ligand binding induces the", "binding induces the dimerization", "induces the dimerization of", "the dimerization of the", "dimerization of the receptor", "of the receptor and", "the receptor and transautophosphorylation", "and transautophosphorylation resulting", "transautophosphorylation resulting in", "resulting in a fully", "in a fully activated", "a fully activated receptor", "fully activated receptor that", "activated receptor that triggers", "receptor that triggers downstream", "that triggers downstream signaling", "triggers downstream signaling cascades", "downstream signaling cascades such", "signaling cascades such as", "cascades such as ras", "as ras pi3k", "ras pi3k and", "pi3k and irs1 signaling.", "and irs1 signaling. alk", "irs1 signaling. alk may", "signaling. alk may also", "alk may also undergo", "may also undergo ligand", "also undergo ligand independent", "undergo ligand independent activation", "ligand independent activation through", "independent activation through rptpb/rptpz", "through rptpb/rptpz deuel", "rptpb/rptpz deuel et", "et al 2013", "al 2013 .", "2013 .

              alk is", ".

              alk is mainly", "

              alk is mainly expressed", "is mainly expressed in", "mainly expressed in the", "expressed in the developing", "in the developing central", "the developing central and", "developing central and peripheral", "central and peripheral nervous", "and peripheral nervous system", "peripheral nervous system and", "nervous system and plays", "system and plays a", "and plays a role", "plays a role in", "a role in differentiation", "role in differentiation during", "in differentiation during development", "during development souttou", "development souttou et", "2001 gouzi et", "2005 degoutin et", "al 2007 .", "2007 . in drosophila", ". in drosophila and", "in drosophila and mice", "and mice alk", "mice alk is", "alk is a thinness", "is a thinness gene", "a thinness gene involved", "thinness gene involved in", "gene involved in the", "involved in the resistance", "in the resistance to", "the resistance to weight", "resistance to weight gain", "weight gain orthofer", "gain orthofer et", "et al 2020", "al 2020 .", "2020 . through activation", ". through activation of", "through activation of stat3", "activation of stat3 targets", "stat3 targets alk", "targets alk also", "alk also appears to", "also appears to play", "appears to play a", "to play a role", "play a role in", "a role in response", "role in response to", "in response to ethanol", "to ethanol hamada", "ethanol hamada et", "al 2021 .", "anaplastic lymphoma kinase alk", "kinase alk is", "alk is a transmembrane", "is a transmembrane receptor tyrosine", "a transmembrane receptor tyrosine kinase", "transmembrane receptor tyrosine kinase that", "tyrosine kinase that along", "kinase that along with", "that along with related", "along with related receptor ltk", "related receptor ltk leukocyte", "receptor ltk leukocyte tyrosine", "ltk leukocyte tyrosine kinase", "tyrosine kinase receptor is", "kinase receptor is a", "receptor is a member", "is a member of the", "a member of the insulin", "member of the insulin receptor", "of the insulin receptor superfamily", "insulin receptor superfamily iwahara", "receptor superfamily iwahara et", "superfamily iwahara et al", "iwahara et al 1997", "et al 1997 .", "al 1997 . alk", "1997 . alk was discovered", ". alk was discovered as", "alk was discovered as an", "was discovered as an oncogene", "discovered as an oncogene in", "as an oncogene in anaplastic", "an oncogene in anaplastic large", "oncogene in anaplastic large cell", "in anaplastic large cell lymphomas", "large cell lymphomas alcls", "alcls but also", "but also plays an oncogenic", "also plays an oncogenic role", "plays an oncogenic role in", "an oncogenic role in other", "oncogenic role in other cancer", "role in other cancer types", "other cancer types such", "cancer types such as", "types such as non", "such as non small cell", "as non small cell lung", "non small cell lung cancer", "cell lung cancer nsclc", "nsclc inflammatory myofibroblastic", "inflammatory myofibroblastic tumours imt", "melanoma neuroblastoma and glioblastoma.", "neuroblastoma and glioblastoma. in cancer", "glioblastoma. in cancer the", "in cancer the chromosomal", "cancer the chromosomal region", "the chromosomal region encoding alk", "chromosomal region encoding alk frequently", "region encoding alk frequently undergoes", "encoding alk frequently undergoes genomic", "alk frequently undergoes genomic rearrangements", "undergoes genomic rearrangements resulting", "genomic rearrangements resulting in", "rearrangements resulting in the", "resulting in the formation of", "in the formation of alk", "the formation of alk fusion", "formation of alk fusion proteins", "alk fusion proteins such", "fusion proteins such as", "proteins such as npm\u2011alk", "such as npm\u2011alk the", "as npm\u2011alk the result", "npm\u2011alk the result of", "the result of a translocation", "result of a translocation event", "a translocation event t", "translocation event t 2", "event t 2 5", "t 2 5 p23", "2 5 p23 q35", "p23 q35 which is", "q35 which is predominant", "which is predominant in alcl", "predominant in alcl and", "in alcl and eml4\u2011alk", "and eml4\u2011alk an inversion", "eml4\u2011alk an inversion event", "an inversion event on chromosome", "inversion event on chromosome 2", "chromosome 2 morris", "2 morris et", "morris et al 1994", "al 1994 couts", "1994 couts et al", "couts et al 2018", "et al 2018 .", "al 2018 . these", "2018 . these fusion proteins", ". these fusion proteins consist", "these fusion proteins consist of", "fusion proteins consist of the", "proteins consist of the c\u2011terminal", "consist of the c\u2011terminal region", "of the c\u2011terminal region of", "the c\u2011terminal region of alk", "region of alk encompassing", "of alk encompassing the", "alk encompassing the kinase", "encompassing the kinase domain and", "the kinase domain and the", "kinase domain and the effector", "domain and the effector protein", "and the effector protein binding", "the effector protein binding domain", "protein binding domain with", "binding domain with loss", "domain with loss of", "with loss of the transmembrane", "loss of the transmembrane domain", "transmembrane domain while", "domain while the", "while the n\u2011terminus of the", "the n\u2011terminus of the fusion", "n\u2011terminus of the fusion protein", "of the fusion protein contains", "the fusion protein contains the", "fusion protein contains the dimerization", "protein contains the dimerization domain", "contains the dimerization domain of", "the dimerization domain of the", "dimerization domain of the partner", "domain of the partner gene.", "of the partner gene. fusion", "the partner gene. fusion proteins", "partner gene. fusion proteins of", "gene. fusion proteins of alk", "fusion proteins of alk are", "proteins of alk are therefore", "of alk are therefore capable", "alk are therefore capable of", "are therefore capable of ligand\u2011independent", "therefore capable of ligand\u2011independent dimerization", "of ligand\u2011independent dimerization resulting", "ligand\u2011independent dimerization resulting in", "dimerization resulting in constitutive", "resulting in constitutive alk signaling", "constitutive alk signaling reviewed", "alk signaling reviewed in", "signaling reviewed in duyster", "reviewed in duyster et al", "duyster et al 2001", "al 2001 chiarle", "2001 chiarle et al", "chiarle et al 2008", "al 2008 della", "2008 della corte et", "corte et al 2018", "al 2018 hallberg", "2018 hallberg and palmer", "hallberg and palmer 2013", "palmer 2013 hallberg", "2013 hallberg and palmer", "hallberg and palmer 2016", "palmer 2016 janoueix", "2016 janoueix larousey et", "larousey et al 2018", "al 2018 ducray", "2018 ducray et al", "ducray et al 2019", "et al 2019 .", "al 2019 . additionally", "2019 . additionally amplification", ". additionally amplification of", "additionally amplification of alk", "amplification of alk and/or point", "of alk and/or point mutations", "alk and/or point mutations leading", "and/or point mutations leading to", "point mutations leading to its", "mutations leading to its constitutive", "leading to its constitutive activation", "to its constitutive activation have", "its constitutive activation have been", "constitutive activation have been detected", "activation have been detected in", "have been detected in neuroblastoma", "detected in neuroblastoma reviewed", "in neuroblastoma reviewed in", "neuroblastoma reviewed in mcduff", "reviewed in mcduff et al", "mcduff et al 2011", "et al 2011 .", "al 2011 .

              many", "2011 .

              many of the", ".

              many of the functional", "

              many of the functional studies", "of the functional studies on", "the functional studies on alk", "functional studies on alk have", "studies on alk have been", "on alk have been conducted", "alk have been conducted in", "have been conducted in the", "been conducted in the context", "conducted in the context of", "in the context of oncogenic", "the context of oncogenic forms", "context of oncogenic forms of", "of oncogenic forms of the", "oncogenic forms of the protein.", "forms of the protein. in", "of the protein. in contrast", "protein. in contrast fewer", "in contrast fewer studies", "contrast fewer studies have", "fewer studies have been conducted", "studies have been conducted on", "have been conducted on the", "been conducted on the wild", "conducted on the wild type", "on the wild type protein", "the wild type protein under", "wild type protein under normal", "type protein under normal physiological", "protein under normal physiological conditions", "normal physiological conditions and", "physiological conditions and indeed", "and indeed alk was", "indeed alk was initially", "alk was initially classed as", "was initially classed as an", "initially classed as an orphan", "classed as an orphan receptor", "as an orphan receptor with", "an orphan receptor with no", "orphan receptor with no identified", "receptor with no identified ligand.", "with no identified ligand. two", "no identified ligand. two small", "identified ligand. two small heparin", "ligand. two small heparin binding", "two small heparin binding growth", "small heparin binding growth factors", "binding growth factors pleiotrophin", "factors pleiotrophin ptn", "pleiotrophin ptn and", "mdk were initially", "were initially identified as potential", "initially identified as potential ligands", "identified as potential ligands however", "as potential ligands however subsequent", "potential ligands however subsequent studies", "ligands however subsequent studies failed", "however subsequent studies failed to", "subsequent studies failed to support", "studies failed to support this", "to support this stoica", "support this stoica et", "this stoica et al", "stoica et al 2001", "al 2001 stoica", "2001 stoica et al", "stoica et al 2002", "al 2002 mathivet", "2002 mathivet et al", "mathivet et al 2007", "al 2007 moog", "2007 moog lutz et", "lutz et al 2005", "al 2005 motegi", "2005 motegi et al", "motegi et al 2004", "al 2004 reviewed", "2004 reviewed in wellstein", "reviewed in wellstein et al", "wellstein et al 2012", "al 2012 winkler", "2012 winkler et al", "winkler et al 2014", "al 2014 herradon", "2014 herradon and perez", "and perez garcia 2014", "perez garcia 2014 .", "garcia 2014 . more", ". more recently alkal1", "more recently alkal1 and", "recently alkal1 and alkal2", "alkal1 and alkal2 also", "and alkal2 also known", "alkal2 also known as", "also known as fam150a and", "known as fam150a and fam150b", "fam150a and fam150b have", "and fam150b have been", "fam150b have been identified", "have been identified as ligands", "been identified as ligands for", "identified as ligands for both", "as ligands for both alk", "ligands for both alk and", "for both alk and the", "both alk and the related", "alk and the related ltk", "and the related ltk receptor", "related ltk receptor albeit", "ltk receptor albeit with", "receptor albeit with differing", "with differing potencies zhang", "differing potencies zhang et", "potencies zhang et al", "zhang et al 2014", "al 2014 guan", "2014 guan et al", "guan et al 2015", "al 2015 reshetnyak", "2015 reshetnyak et al", "reshetnyak et al 2015", "reshetnyak et al 2018", "al 2018 fadeev", "2018 fadeev et al", "fadeev et al 2018", "al 2018 reshetnyak", "2018 reshetnyak et al", "reshetnyak et al 2021", "al 2021 de", "2021 de munck et", "munck et al 2021", "al 2021 borenas", "2021 borenas et al", "borenas et al 2021", "al 2021 reviewed", "2021 reviewed in hallberg", "reviewed in hallberg and palmer", "and palmer 2016 .", "palmer 2016 . whereas", "2016 . whereas ltk receptor", ". whereas ltk receptor is", "whereas ltk receptor is potently", "ltk receptor is potently activated", "receptor is potently activated by", "is potently activated by both", "potently activated by both alkal1", "activated by both alkal1 and", "by both alkal1 and alkal2", "alkal1 and alkal2 alk", "and alkal2 alk is", "alkal2 alk is only", "alk is only weakly stimulated", "is only weakly stimulated by", "only weakly stimulated by alkal1", "stimulated by alkal1 reshetnyak", "by alkal1 reshetnyak et", "alkal1 reshetnyak et al", "al 2018 . ligand", "2018 . ligand binding induces", ". ligand binding induces the", "ligand binding induces the dimerization", "binding induces the dimerization of", "induces the dimerization of the", "the dimerization of the receptor", "dimerization of the receptor and", "of the receptor and transautophosphorylation", "receptor and transautophosphorylation resulting", "and transautophosphorylation resulting in", "transautophosphorylation resulting in a", "resulting in a fully activated", "in a fully activated receptor", "a fully activated receptor that", "fully activated receptor that triggers", "activated receptor that triggers downstream", "receptor that triggers downstream signaling", "that triggers downstream signaling cascades", "triggers downstream signaling cascades such", "downstream signaling cascades such as", "signaling cascades such as ras", "such as ras pi3k", "as ras pi3k and", "ras pi3k and irs1", "pi3k and irs1 signaling. alk", "and irs1 signaling. alk may", "irs1 signaling. alk may also", "signaling. alk may also undergo", "alk may also undergo ligand", "may also undergo ligand independent", "also undergo ligand independent activation", "undergo ligand independent activation through", "ligand independent activation through rptpb/rptpz", "activation through rptpb/rptpz deuel", "through rptpb/rptpz deuel et", "rptpb/rptpz deuel et al", "deuel et al 2013", "et al 2013 .", "al 2013 .

              alk", "2013 .

              alk is mainly", ".

              alk is mainly expressed", "

              alk is mainly expressed in", "is mainly expressed in the", "mainly expressed in the developing", "expressed in the developing central", "in the developing central and", "the developing central and peripheral", "developing central and peripheral nervous", "central and peripheral nervous system", "and peripheral nervous system and", "peripheral nervous system and plays", "nervous system and plays a", "system and plays a role", "and plays a role in", "plays a role in differentiation", "a role in differentiation during", "role in differentiation during development", "differentiation during development souttou", "during development souttou et", "development souttou et al", "souttou et al 2001", "al 2001 gouzi", "2001 gouzi et al", "gouzi et al 2005", "al 2005 degoutin", "2005 degoutin et al", "degoutin et al 2007", "et al 2007 .", "al 2007 . in", "2007 . in drosophila and", ". in drosophila and mice", "drosophila and mice alk", "and mice alk is", "mice alk is a", "alk is a thinness gene", "is a thinness gene involved", "a thinness gene involved in", "thinness gene involved in the", "gene involved in the resistance", "involved in the resistance to", "in the resistance to weight", "the resistance to weight gain", "to weight gain orthofer", "weight gain orthofer et", "gain orthofer et al", "orthofer et al 2020", "et al 2020 .", "al 2020 . through", "2020 . through activation of", ". through activation of stat3", "through activation of stat3 targets", "of stat3 targets alk", "stat3 targets alk also", "targets alk also appears", "alk also appears to play", "also appears to play a", "appears to play a role", "to play a role in", "play a role in response", "a role in response to", "role in response to ethanol", "response to ethanol hamada", "to ethanol hamada et", "ethanol hamada et al", "hamada et al 2021", "et al 2021 ." ] }, { "record_id": "GLY_000594_1_1899", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", 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ridley 2018 .", "ridley 2018 . rhob", "2018 . rhob regulated", ". rhob regulated cellular", "rhob regulated cellular processes", "regulated cellular processes are", "cellular processes are important", "processes are important for", "are important for the", "important for the immune", "for the immune system", "the immune system function", "system function vega", "function vega and", "2018 pulmonary", "gas exchange wojciak", "exchange wojciak stothard", "wojciak stothard et al.", "stothard et al. 2012", "al. 2012 vega", "2012 vega and", "and angiogenesis and vascular", "angiogenesis and vascular function", "vascular function vega", "2018 . rhob has", ". rhob has been", "rhob has been implicated", "has been implicated both", "been implicated both as", "implicated both as a", "both as a tumor", "as a tumor suppressor", "a tumor suppressor and", "tumor suppressor and as", "suppressor and as an", "and as an oncogene", "as an oncogene in", "an oncogene in cancer", "in cancer prendergast", "cancer prendergast 2001", "prendergast 2001 huang", "2001 huang and", "huang and prendergast 2006", "prendergast 2006 ju", "2006 ju and", "ju and gilkes 2018", "gilkes 2018 calvayrac", "2018 calvayrac et", "calvayrac et al. 2018", "et al. 2018 .", "this pathway catalogues rhob guanine", "pathway catalogues rhob guanine nucleotide", "catalogues rhob guanine nucleotide exchange", "rhob guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "gefs gtpase activator", "gtpase activator proteins gaps", "gaps gdp dissociation", "gdp dissociation inhibitors gdis", "inhibitors gdis and", "gdis and rhob effectors.", "and rhob effectors. rhob belongs", "rhob effectors. rhob belongs to", "effectors. rhob belongs to the", "rhob belongs to the rhoa", "belongs to the rhoa subfamily", "to the rhoa subfamily of", "the rhoa subfamily of rho", "rhoa subfamily of rho gtpases", "subfamily of rho gtpases and", "of rho gtpases and shares", "rho gtpases and shares 85%", "gtpases and shares 85% sequence", "and shares 85% sequence identity", "shares 85% sequence identity with", "85% sequence identity with rhoa", "sequence identity with rhoa and", "identity with rhoa and rhoc.", "with rhoa and rhoc. posttranslational", "rhoa and rhoc. posttranslational modifications", "and rhoc. posttranslational modifications of", "rhoc. posttranslational modifications of the", "posttranslational modifications of the unique", "modifications of the unique c", "of the unique c terminus", "the unique c terminus of", "unique c terminus of rhob", "c terminus of rhob regulate", "terminus of rhob regulate its", "of rhob regulate its subcellular", "rhob regulate its subcellular localization.", "regulate its subcellular localization. similar", "its subcellular localization. similar to", "subcellular localization. similar to rhoa", "localization. similar to rhoa and", "similar to rhoa and rhoc", "rhoa and rhoc rhob", "and rhoc rhob regulates", "rhoc rhob regulates the", "rhob regulates the 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2018 .", "and ridley 2018 . rhob", "ridley 2018 . rhob regulated", "2018 . rhob regulated cellular", ". rhob regulated cellular processes", "rhob regulated cellular processes are", "regulated cellular processes are important", "cellular processes are important for", "processes are important for the", "are important for the immune", "important for the immune system", "for the immune system function", "immune system function vega", "system function vega and", "function vega and ridley", "ridley 2018 pulmonary", "2018 pulmonary gas", "pulmonary gas exchange wojciak", "gas exchange wojciak stothard", "exchange wojciak stothard et", "wojciak stothard et al. 2012", "et al. 2012 vega", "al. 2012 vega and", "2012 vega and ridley", "2018 and angiogenesis", "and angiogenesis and vascular function", "and vascular function vega", "vascular function vega and", "ridley 2018 . rhob has", "2018 . rhob has been", ". rhob has been implicated", "rhob has been implicated both", "has been implicated both 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. rhoc contributes", "2018 . rhoc contributes to", ". rhoc contributes to invasiveness", "rhoc contributes to invasiveness and", "contributes to invasiveness and metastatic", "to invasiveness and metastatic potential", "invasiveness and metastatic potential of", "and metastatic potential of cancer", "metastatic potential of cancer cells", "of cancer cells bravo", "cancer cells bravo cordero", "cells bravo cordero et", "bravo cordero et al. 2014", "et al. 2014 guan", "al. 2014 guan et", "2014 guan et al.", "et al. 2018 thomas", "al. 2018 thomas et", "2018 thomas et al.", "thomas et al. 2019 ." ] }, { "record_id": "GLY_000594_1_1902", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013148", "r hsa", "hsa 9013148", "r hsa 9013148" ] }, { "record_id": "GLY_000594_1_1902", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cdc42 gtpase", "gtpase cycle", "cdc42 gtpase cycle", "this pathway", "pathway 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intracellular", "impair intracellular trafficking", "trafficking egorov", "egorov and polishchuk", "and polishchuk 2017", "polishchuk 2017 .", "2017 . cdc42", ". cdc42 participates", "cdc42 participates in", "participates in insulin", "in insulin synthesis", "insulin synthesis and", "synthesis and secretion", "and secretion and", "secretion and contributes", "and contributes to", "contributes to the", "to the pathogenesis", "the pathogenesis of", "pathogenesis of insulin", "of insulin resistance", "insulin resistance and", "resistance and diabetic", "and diabetic nephropathy", "nephropathy huang", "huang et al.", "cdc42 is often", "is often dysregulated", "often dysregulated in", "dysregulated in cancer", "in cancer because", "cancer because a", "because a number", "a number of", "number of gefs", "of gefs and", "gefs and gef", "and gef activators", "gef activators that", "activators that act", "that act upstream", "act upstream of", "upstream of rac1", "of rac1 and", "rac1 and cdc42", "and cdc42 are", "cdc42 are known", "are known oncogenes", "oncogenes aguilar", "aguilar et al.", "et al. 2017", "2017 maldonado", "maldonado et al.", "2018 zhang", "zhang et al.", "2019 maldonado", "et al. 2020", "al. 2020 .", "2020 . cdc4", ". cdc4 promotes", "cdc4 promotes cancer", "promotes cancer cell", "cancer cell proliferation", "proliferation survival", "survival invasion", "invasion migration", "migration and metastasis", "metastasis xiao", "especially under hyperglycemia", "hyperglycemia huang", "this pathway catalogues cdc42", "pathway catalogues cdc42 guanine", "catalogues cdc42 guanine nucleotide", "cdc42 guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs gtpase", "activator proteins gaps", "gaps gdp", "dissociation inhibitors gdis", "gdis and cdc42", "and cdc42 effectors. cdc42", "cdc42 effectors. cdc42 is", "effectors. cdc42 is one", "cdc42 is one of", "is one of the", "one of the three", "of the three best", "the three best characterized", "three best characterized rho", "best characterized rho gtpases", "rho gtpases the", "gtpases the other", "the other two being", "other two being rhoa", "two being rhoa and", "being rhoa and rac1.", "rhoa and rac1. by", "and rac1. by regulating", "rac1. by regulating the", "by regulating the cytoskeleton", "the cytoskeleton cdc42", "cytoskeleton cdc42 regulates", "cdc42 regulates cell polarity", "regulates cell polarity across", "cell polarity across different", "polarity across different species", "different species from", "species from yeast", "from yeast to humans", "to humans pichaud", "humans pichaud et", "pichaud et al. 2019", "al. 2019 woods", "2019 woods and", "woods and lew 2019", "and lew 2019 .", "lew 2019 . cdc42", "2019 . cdc42 is", ". cdc42 is an", "cdc42 is an essential", "is an essential regulator", "an essential regulator of", "essential regulator of polarized", "regulator of polarized morphogenesis", "of polarized morphogenesis in", "polarized 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"part in the regulation", "in the regulation of", "the regulation of membrane", "regulation of membrane trafficking.", "of membrane trafficking. dysfunction", "membrane trafficking. dysfunction of", "trafficking. dysfunction of several", "dysfunction of several cdc42", "of several cdc42 specific", "several cdc42 specific gefs", "cdc42 specific gefs has", "specific gefs has been", "gefs has been shown", "has been shown to", "been shown to impair", "shown to impair intracellular", "to impair intracellular trafficking", "intracellular trafficking egorov", "trafficking egorov and", "egorov and polishchuk 2017", "and polishchuk 2017 .", "polishchuk 2017 . cdc42", "2017 . cdc42 participates", ". cdc42 participates in", "cdc42 participates in insulin", "participates in insulin synthesis", "in insulin synthesis and", "insulin synthesis and secretion", "synthesis and secretion and", "and secretion and contributes", "secretion and contributes to", "and contributes to the", "contributes to the pathogenesis", "to the pathogenesis of", "the pathogenesis of insulin", "pathogenesis of insulin resistance", "of insulin resistance and", "insulin resistance and diabetic", "resistance and diabetic nephropathy", "diabetic nephropathy huang", "nephropathy huang et", "huang et al. 2019", ". cdc42 is often", "cdc42 is often dysregulated", "is often dysregulated in", "often dysregulated in cancer", "dysregulated in cancer because", "in cancer because a", "cancer because a number", "because a number of", "a number of gefs", "number of gefs and", "of gefs and gef", "gefs and gef activators", "and gef activators that", "gef activators that act", "activators that act upstream", "that act upstream of", "act upstream of rac1", "upstream of rac1 and", "of rac1 and cdc42", "rac1 and cdc42 are", "and cdc42 are known", "cdc42 are known oncogenes", "known oncogenes aguilar", "oncogenes aguilar et", "aguilar et al. 2017", "al. 2017 maldonado", "2017 maldonado et", "maldonado et al. 2018", "al. 2018 zhang", "2018 zhang et", "zhang et al. 2019", "al. 2019 maldonado", "2019 maldonado et", "maldonado et al. 2020", "et al. 2020 .", "al. 2020 . cdc4", "2020 . cdc4 promotes", ". cdc4 promotes cancer", "cdc4 promotes cancer cell", "promotes cancer cell proliferation", "cell proliferation survival", "invasion migration and", "and metastasis xiao", "metastasis xiao et", "2018 especially", "under hyperglycemia huang", "hyperglycemia huang et", "this pathway catalogues cdc42 guanine", "pathway catalogues cdc42 guanine nucleotide", "catalogues cdc42 guanine nucleotide exchange", "cdc42 guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "gefs gtpase activator", "gtpase activator proteins gaps", "gaps gdp dissociation", "gdp dissociation inhibitors gdis", "inhibitors gdis and", "gdis and cdc42 effectors.", "and cdc42 effectors. cdc42 is", "cdc42 effectors. cdc42 is one", "effectors. cdc42 is one of", "cdc42 is one of the", "is one of the three", "one of the three best", 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in the pathogenesis", "involved in the pathogenesis of", "in the pathogenesis of psoriasis", "pathogenesis of psoriasis winge", "of psoriasis winge and", "psoriasis winge and marinkovich", "winge and marinkovich 2019 .", "and marinkovich 2019 . rac1", "marinkovich 2019 . rac1 is", "2019 . rac1 is essential", ". rac1 is essential to", "rac1 is essential to vascular", "is essential to vascular homeostasis", "essential to vascular homeostasis and", "to vascular homeostasis and chronically", "vascular homeostasis and chronically elevated", "homeostasis and chronically elevated rac1", "and chronically elevated rac1 signaling", "chronically elevated rac1 signaling contributes", "elevated rac1 signaling contributes to", "rac1 signaling contributes to vascular", "signaling contributes to vascular pathology", "to vascular pathology marinkovic", "vascular pathology marinkovic et", "pathology marinkovic et al.", "marinkovic et al. 2015 .", "et al. 2015 . rac1", "al. 2015 . rac1 hyperactivation", ". rac1 hyperactivation mutation", "rac1 hyperactivation mutation and", "hyperactivation mutation and copy", "mutation and copy number gain", "and copy number gain are", "copy number gain are frequently", "number gain are frequently observed", "gain are frequently observed in", "are frequently observed in solid", "frequently observed in solid tumors", "in solid tumors zou", "solid tumors zou et", "tumors zou et al.", "et al. 2017 de", "al. 2017 de et", "2017 de et al.", "et al. 2019 de", "al. 2019 de et", "2019 de et al.", "et al. 2020 cannon", "al. 2020 cannon et", "2020 cannon et al.", "et al. 2020 kotelevets", "al. 2020 kotelevets and", "2020 kotelevets and chastre" ] }, { "record_id": "GLY_000594_1_1904", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013404", "r hsa", "hsa 9013404", "r hsa 9013404" ] }, { "record_id": "GLY_000594_1_1904", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ 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lougaris et", "2013 lougaris et al.", "lougaris et al. 2020 ." ] }, { "record_id": "GLY_000594_1_1905", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013405", "r hsa", "hsa 9013405", "r hsa 9013405" ] }, { "record_id": "GLY_000594_1_1905", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhod gtpase", "gtpase cycle", "rhod gtpase cycle", "this pathway", "pathway catalogues", "catalogues rhod", "gtpase activator", "activator proteins", "and rhod", "rhod effectors.", "effectors. rhod", "rhod possesses", "possesses gtpase", "gtpase activity", "activity and", "and is", "is therefore", "therefore grouped", "grouped with", "with classical", "classical rho", "rho gtpases", "gtpases but", "but it", "it is", "is atypical", "atypical in", "in the", "the sense", "sense that", "that no", "no known", "known guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "and no", "no gdp", "gdp 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"movement of endosomes gasman", "of endosomes gasman et", "endosomes gasman et al.", "et al. 2003 reviewed", "al. 2003 reviewed in", "2003 reviewed in randazzo", "reviewed in randazzo 2003 ." ] }, { "record_id": "GLY_000594_1_1906", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013406", "r hsa", "hsa 9013406", "r hsa 9013406" ] }, { "record_id": "GLY_000594_1_1906", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhoq gtpase", "gtpase cycle", "rhoq gtpase cycle", "this pathway", "pathway catalogues", "catalogues rhoq", "also known", "known as", "as tc10", "guanine nucleotide", "nucleotide exchange", "exchange factors", "gtpase activator", "activator proteins", "and rhoq", "rhoq effectors.", "effectors. no", "no gdp", "gdp dissociation", "dissociation inhibitors", "have been", "been shown", "shown to", "to interact", "interact with", "with rhoq.", "rhoq. two", "two gdis", "as rho", "rho gdi", 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murphy", "al. 2001 .", "this pathway catalogues rhoq", "catalogues rhoq also", "rhoq also known", "also known as tc10", "as tc10 guanine", "tc10 guanine nucleotide", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs gtpase", "activator proteins gaps", "gaps and", "and rhoq effectors. no", "rhoq effectors. no gdp", "effectors. no gdp dissociation", "no gdp dissociation inhibitors", "dissociation inhibitors gdis", "gdis have been", "have been shown to", "been shown to interact", "shown to interact with", "to interact with rhoq.", "interact with rhoq. two", "with rhoq. two gdis", "two gdis arhgdia", "arhgdia also known", "also known as rho", "known as rho gdi", "as rho gdi alpha", "alpha michaelson", "michaelson et al. 2001", "al. 2001 murphy", "2001 murphy et", "murphy et al. 2001", "al. 2001 and", "2001 and arhgdib", "and arhgdib also", "arhgdib also known", "also known as d4", "known as d4 gdi", "gdi zhang", "zhang et al. 2009", "2009 were", "were specifically shown 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vesicles and", "exocytosing vesicles and recycling", "vesicles and recycling endosomes.", "and recycling endosomes. rhoq", "recycling endosomes. rhoq gtpase", "endosomes. rhoq gtpase activity", "rhoq gtpase activity is", "gtpase activity is necessary", "activity is necessary for", "is necessary for fusion", "necessary for fusion of", "for fusion of vesicles", "fusion of vesicles with", "of vesicles with the", "vesicles with the plasma", "with the plasma membrane", "plasma membrane kawase", "membrane kawase et", "kawase et al. 2006", "al. 2006 donnelly", "2006 donnelly et", "et al. 2014 .", "al. 2014 . rhoq", "2014 . rhoq is", ". rhoq is required", "rhoq is required for", "is required for insulin", "required for insulin stimulated", "for insulin stimulated glucose", "insulin stimulated glucose uptake", "glucose uptake kanzaki", "uptake kanzaki and", "kanzaki and pessin 2003", "pessin 2003 saltiel", "2003 saltiel and", "saltiel and pessin 2003", "pessin 2003 and", "2003 and is", "and is involved in", "is involved in insulin", "involved in insulin signaling", "in insulin signaling in", "insulin signaling in adipocytes", "in adipocytes satoh", "adipocytes satoh 2014", "satoh 2014 . while", "2014 . while some", ". while some studies", "while some studies reported", "some studies reported rhoq", "studies reported rhoq involvement", "reported rhoq involvement in", "rhoq involvement in neurite", "involvement in neurite outgrowth", "neurite outgrowth abe", "outgrowth abe et", "abe et al. 2003", "al. 2003 gonzalez\u2010billault", "2003 gonzalez\u2010billault et", "gonzalez\u2010billault et al. 2012", "al. 2012 and", "2012 and regulation", "and regulation of membrane", "regulation of membrane addition", "of membrane addition during", "membrane addition during axon", "addition during axon formation", "axon formation dupraz", "formation dupraz et", "dupraz et al. 2009", "al. 2009 gonzalez\u2010billault", "2009 gonzalez\u2010billault et", "2012 other", "other studies failed to", "studies failed to identify", "failed to identify rhoq", "to identify rhoq as", "identify rhoq as a", "rhoq as a regulator", "as a regulator of", "a regulator of neurite", "regulator of neurite outgrowth", "neurite outgrowth murphy", "outgrowth murphy et", "al. 1999 murphy", "1999 murphy et", "et al. 2001 .", "pathway catalogues rhoq also", "catalogues rhoq also known", "rhoq also known as", "known as tc10 guanine", "as tc10 guanine nucleotide", "tc10 guanine nucleotide exchange", "nucleotide exchange factors gefs", "gefs gtpase activator", "gtpase activator proteins gaps", "gaps and rhoq", "and rhoq effectors. no gdp", "rhoq effectors. no gdp dissociation", "effectors. no gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "inhibitors gdis have", "gdis have been shown", "have been shown to interact", "been shown to interact with", "shown to interact with rhoq.", "to interact with rhoq. two", "interact with rhoq. two gdis", "rhoq. two gdis arhgdia", "gdis arhgdia also", "arhgdia also known as", "also known as rho gdi", "known as rho gdi alpha", "gdi alpha michaelson", "alpha michaelson et", "et al. 2001 murphy", "al. 2001 murphy et", "2001 murphy et al.", "et al. 2001 and", "al. 2001 and arhgdib", "and arhgdib also known", "arhgdib also known as", "also known as d4 gdi", "d4 gdi zhang", "gdi zhang et", "al. 2009 were", "2009 were specifically", "were specifically shown not to", "specifically shown not to interact", "shown not to interact with", "not to interact with rhoq.", "to interact with rhoq. rhoq", "with rhoq. rhoq together", "rhoq. rhoq together with", "rhoq together with rhoj", "together with rhoj tcl", "tcl belongs to", "belongs to the cdc42 subfamily", "to the cdc42 subfamily of", "the cdc42 subfamily of rho", "cdc42 subfamily of rho gtpases", "of rho gtpases with", "rho gtpases with the", "gtpases with the three", "with the three family members", "the three family members sharing", "three family members sharing 65", "family members sharing 65 85%", "members sharing 65 85% of", "sharing 65 85% of homology", "85% of homology murphy", "of homology murphy et", "homology murphy et al.", "et al. 1999 vignal", "al. 1999 vignal et", "1999 vignal et al.", "et al. 2000 donnelly", "al. 2000 donnelly et", "2000 donnelly et al.", "et al. 2014 shi", "al. 2014 shi et", "2014 shi et al.", "shi et al. 2016 .", "et al. 2016 . rhoq", "al. 2016 . rhoq is", "2016 . rhoq is highly", ". rhoq is highly activated", "rhoq is highly activated on", "is highly activated on exocytosing", "highly activated on exocytosing vesicles", "activated on exocytosing vesicles and", "on exocytosing vesicles and recycling", "exocytosing vesicles and recycling endosomes.", "vesicles and recycling endosomes. rhoq", "and recycling endosomes. rhoq gtpase", "recycling endosomes. rhoq gtpase activity", "endosomes. rhoq gtpase activity is", "rhoq gtpase activity is necessary", "gtpase activity is necessary for", "activity is necessary for fusion", "is necessary for fusion of", "necessary for fusion of vesicles", "for fusion of vesicles with", "fusion of vesicles with the", "of vesicles with the plasma", "vesicles with the plasma membrane", "the plasma membrane kawase", "plasma membrane kawase et", "membrane kawase et al.", "et al. 2006 donnelly", "al. 2006 donnelly et", "2006 donnelly et al.", "donnelly et al. 2014 .", "et al. 2014 . rhoq", "al. 2014 . rhoq is", "2014 . rhoq is required", ". rhoq is required for", "rhoq is required for insulin", "is required for insulin stimulated", "required for insulin stimulated glucose", "for insulin stimulated glucose uptake", "stimulated glucose uptake kanzaki", "glucose uptake kanzaki and", "uptake kanzaki and pessin", "and pessin 2003 saltiel", "pessin 2003 saltiel and", "2003 saltiel and pessin", "and pessin 2003 and", "pessin 2003 and is", "2003 and is involved", "and is involved in insulin", "is involved in insulin signaling", "involved in insulin signaling in", "in insulin signaling in adipocytes", "signaling in adipocytes satoh", "in adipocytes satoh 2014", "adipocytes satoh 2014 .", "satoh 2014 . while some", "2014 . while some studies", ". while some studies reported", "while some studies reported rhoq", "some studies reported rhoq involvement", "studies reported rhoq involvement in", "reported rhoq involvement in neurite", "rhoq involvement in neurite outgrowth", "in neurite outgrowth abe", "neurite outgrowth abe et", "outgrowth abe et al.", "et al. 2003 gonzalez\u2010billault", "al. 2003 gonzalez\u2010billault et", "2003 gonzalez\u2010billault et al.", "et al. 2012 and", "al. 2012 and regulation", "2012 and regulation of", "and regulation of membrane addition", "regulation of membrane addition during", "of membrane addition during axon", "membrane addition during axon formation", "during axon formation dupraz", "axon formation dupraz et", "formation dupraz et al.", "et al. 2009 gonzalez\u2010billault", "al. 2009 gonzalez\u2010billault et", "2009 gonzalez\u2010billault et al.", "al. 2012 other", "2012 other studies", "other studies failed to identify", "studies failed to identify rhoq", "failed to identify rhoq as", "to identify rhoq as a", "identify rhoq as a regulator", "rhoq as a regulator of", "as a regulator of neurite", "a regulator of neurite outgrowth", "of neurite outgrowth murphy", "neurite outgrowth murphy et", "outgrowth murphy et al.", "et al. 1999 murphy", "al. 1999 murphy et", "1999 murphy et al.", "murphy et al. 2001 ." ] }, { "record_id": "GLY_000594_1_1907", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013408", "r hsa", "hsa 9013408", "r hsa 9013408" ] }, { "record_id": "GLY_000594_1_1907", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhog gtpase", "gtpase cycle", "rhog gtpase cycle", "this pathway", "pathway catalogues", "catalogues rhog", "rhog guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "gtpase 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rhoj is", "rhoj is highly", "is highly expressed", "highly expressed in", "expressed in endothelial", "in endothelial cells", "cells regulating", "regulating their motility", "their motility and", "and consequently", "consequently vascular", "morphogenesis leszczynska", "leszczynska et al.", "et al. 2011", "2011 shi", "2016 . as", ". as a", "as a part", "a part of", "part of the", "of the vegf", "the vegf signaling", "vegf signaling cascade", "cascade rhoj", "rhoj promotes retinal", "promotes retinal angiogenesis", "angiogenesis fukushima", "fukushima et al.", "et al. 2013", "al. 2013 .", "2013 . rhoj", ". rhoj plays", "rhoj plays a", "plays a role", "a role in", "role in cancer", "in cancer cell", "cancer cell migration", "cell migration and", "migration and cancer", "and cancer related", "cancer related angiogenesis", "angiogenesis shi", "rhoj is involved", "is involved in", "involved in adipocyte", "in adipocyte differentiation", "differentiation nishizuka", "2003 shi", "this 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and", "motility and consequently", "consequently vascular morphogenesis", "vascular morphogenesis leszczynska", "morphogenesis leszczynska et", "leszczynska et al. 2011", "al. 2011 shi", "2011 shi et", "al. 2016 . as", "2016 . as a", ". as a part", "as a part of", "a part of the", "part of the vegf", "of the vegf signaling", "the vegf signaling cascade", "signaling cascade rhoj", "cascade rhoj promotes", "rhoj promotes retinal angiogenesis", "retinal angiogenesis fukushima", "angiogenesis fukushima et", "fukushima et al. 2013", "et al. 2013 .", "al. 2013 . rhoj", "2013 . rhoj plays", ". rhoj plays a", "rhoj plays a role", "plays a role in", "a role in cancer", "role in cancer cell", "in cancer cell migration", "cancer cell migration and", "cell migration and cancer", "migration and cancer related", "and cancer related angiogenesis", "related angiogenesis shi", "angiogenesis shi et", ". rhoj is involved", "rhoj is involved in", "is involved in adipocyte", "involved in adipocyte differentiation", "adipocyte differentiation nishizuka", "differentiation nishizuka 2003", "nishizuka 2003 shi", "2003 shi et", "pathway catalogues rhoj also", "catalogues rhoj also known", "rhoj also known as", "also known as tcl or", "known as tcl or rhoi", "tcl or rhoi guanine", "or rhoi guanine nucleotide", "rhoi guanine nucleotide exchange", "nucleotide exchange factors gefs", "gefs gtpase activator", "gtpase activator proteins gaps", "gaps and rhoj", "and rhoj effectors. no gdp", "rhoj effectors. no gdp dissociation", "effectors. no gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "inhibitors gdis have", "gdis have been shown", "have been shown to interact", "been shown to interact with", "shown to interact with rhoj.", "to interact with rhoj. rhoj", "with rhoj. rhoj together", "rhoj. rhoj together with", "rhoj together with rhoq", "together with rhoq tc10", "tc10 belongs to", "belongs to the cdc42 subfamily", "to the cdc42 subfamily of", "the cdc42 subfamily of rho", "cdc42 subfamily of rho gtpases", "subfamily of rho gtpases and", "of rho gtpases and shares", "rho gtpases and shares 85%", "gtpases and shares 85% and", "and shares 85% and 78%", "shares 85% and 78% amino", "85% and 78% amino acid", "and 78% amino acid similarity", "78% amino acid similarity with", "amino acid similarity with rhoq", "acid similarity with rhoq and", "similarity with rhoq and cdc42", "rhoq and cdc42 respectively", "cdc42 respectively vignal", "respectively vignal et al.", "vignal et al. 2000 .", "et al. 2000 . rhoj", "al. 2000 . rhoj regulates", "2000 . rhoj regulates the", ". rhoj regulates the cytoskeleton", "regulates the cytoskeleton including", "the cytoskeleton including formation", "cytoskeleton including formation of", "including formation of lamellipodia and", "formation of lamellipodia and actin", "of lamellipodia and actin filaments", "and actin filaments vignal", "actin filaments vignal et", "filaments vignal et al.", "et al. 2000 abe", "al. 2000 abe et", "2000 abe et al.", "et al. 2003 aspenstrom", "al. 2003 aspenstrom et", "2003 aspenstrom et al.", "et al. 2004 shi", "al. 2004 shi et", "2004 shi et al.", "shi et al. 2016 .", "et al. 2016 . rhoj", "al. 2016 . rhoj is", "2016 . rhoj is highly", ". rhoj is highly expressed", "rhoj is highly expressed in", "is highly expressed in endothelial", "highly expressed in endothelial cells", "in endothelial cells regulating", "endothelial cells regulating their", "cells regulating their motility", "their motility and consequently", "and consequently vascular", "vascular morphogenesis leszczynska et", "morphogenesis leszczynska et al.", "et al. 2011 shi", "al. 2011 shi et", "2011 shi et al.", "et al. 2016 . as", "al. 2016 . as a", "2016 . as a part", ". as a part of", "as a part of the", "a part of the vegf", "part of the vegf signaling", "of the vegf signaling cascade", "vegf signaling cascade rhoj", "signaling cascade rhoj promotes", "cascade rhoj promotes retinal", "promotes retinal angiogenesis fukushima", "retinal angiogenesis fukushima et", "angiogenesis fukushima et al.", "fukushima et al. 2013 .", "et al. 2013 . rhoj", "al. 2013 . rhoj plays", "2013 . rhoj plays a", ". rhoj plays a role", "rhoj plays a role in", "plays a role in cancer", "a role in cancer cell", "role in cancer cell migration", "in cancer cell migration and", "cancer cell migration and cancer", "cell migration and cancer related", "migration and cancer related angiogenesis", "cancer related angiogenesis shi", "related angiogenesis shi et", "angiogenesis shi et al.", "2016 . rhoj is involved", ". rhoj is involved in", "rhoj is involved in adipocyte", "is involved in adipocyte differentiation", "in adipocyte differentiation nishizuka", "adipocyte differentiation nishizuka 2003", "nishizuka 2003 shi et", "2003 shi et al." ] }, { "record_id": "GLY_000594_1_1909", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013420", "r hsa", "hsa 9013420", "r hsa 9013420" ] }, { "record_id": "GLY_000594_1_1909", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhou gtpase", "gtpase cycle", "rhou gtpase cycle", "rho gtpase", "gtpase rhou", "wrch 1", "possesses a", "a high", "high intrinsic", "intrinsic guanine", "guanine nucleotide", "nucleotide exchange", "exchange activity", "activity and", "and is", "is constitutively", "constitutively present", "present in", "in the", "the active", "active gtp", "gtp bound", "bound state", "state in", "the absence", "absence of", "of guanine", "exchange factors", "shutes et", "et al.", "al. 2004", "saras et", "2004 .", ". rhou", "rhou does", "does not", "not possess", "possess a", "a gtpase", "gtpase activity", "rhou has", "has been", "been reported", "reported to", "to interact", "interact with", "with some", "some gtpase", "gtpase activator", "activator proteins", "bagci et", "al. 2020", "which may", "may serve", "serve as", "as effectors", "effectors 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              for", ".
              for review", "please refer", "refer to", "to faure", "faure and", "and fort", "fort 2015", "and hodge", "hodge and", "and ridley", "ridley 2020.", "rho gtpase rhou", "rhou wrch", "1 possesses", "possesses a high", "a high intrinsic", "high intrinsic guanine", "intrinsic guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange activity", "exchange activity and", "activity and is", "and is constitutively", "is constitutively present", "constitutively present in", "present in the", "in the active", "the active gtp", "active gtp bound", "gtp bound state", "bound state in", "state in the", "in the absence", "the absence of", "absence of guanine", "of guanine nucleotide", "nucleotide exchange factors", "factors gefs", "shutes et al.", "et al. 2004", "2004 saras", "saras et al.", "al. 2004 .", "2004 . rhou", ". rhou does", "rhou does not", "does not possess", "not possess a", "possess a gtpase", "a gtpase activity", "activity saras", ". rhou has", "rhou has been", "has been reported", "been reported to", "reported to interact", "to interact with", "interact with some", "with some gtpase", "some gtpase activator", "gtpase activator proteins", "proteins gaps", "bagci et al.", "et al. 2020", "which may serve", "may serve as", "serve as effectors", "as effectors that", "effectors that enable", "that enable cross", "enable cross talk", "cross talk with", "talk with other", "with other rho", "other rho gtpases.", "rho gtpases. rhou", "gtpases. rhou was", "rhou was shown", "was shown to", "shown to regulate", "to regulate cytoskeletal", "regulate cytoskeletal dynamics", "dynamics cell", "cell migration and", "migration and adhesion.", "and adhesion. rhou", "adhesion. rhou is", "rhou is expressed", "is expressed during", "expressed during embryonic", "during embryonic development", "embryonic development and", "development and regulates", "and regulates cardiac", "cardiac dickover", "dickover et al.", "et al. 2014", "2014 and", "intestinal slaymi", "slaymi et al.", "et al. 2019", "2019 development.", "development. rhou activates", "rhou activates jnk", "activates jnk and", "jnk and akt", "and akt signaling", "akt signaling during", "signaling during cell", "during cell migration", "migration chuang", "chuang et al.", "et al. 2007", "al. 2007 .
              for", "2007 .
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              for", "al. 2007 .
              for review", ".
              for review please", "review please refer", "please refer to faure", "refer to faure and", "to faure and fort", "faure and fort 2015", "fort 2015 and", "2015 and hodge", "and hodge and ridley", "hodge and ridley 2020.", "rho gtpase rhou wrch", "gtpase rhou wrch 1", "wrch 1 possesses a", "1 possesses a high", "possesses a high intrinsic guanine", "a high intrinsic guanine nucleotide", "high intrinsic guanine nucleotide exchange", "intrinsic guanine nucleotide exchange activity", "guanine nucleotide exchange activity and", "nucleotide exchange activity and is", "exchange activity and is constitutively", "activity and is constitutively present", "and is constitutively present in", "is constitutively present in the", "constitutively present in the active", "present in the active gtp", "in the active gtp bound", "the active gtp bound state", "active gtp bound state in", "gtp bound state in the", "bound state in the absence", "state in the absence of", "in the absence of guanine", "the absence of guanine nucleotide", "absence of guanine nucleotide exchange", "of guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "gefs shutes et", "et al. 2004 saras", "al. 2004 saras et", "2004 saras et al.", "saras et al. 2004 .", "et al. 2004 . rhou", "al. 2004 . rhou does", "2004 . rhou does not", ". rhou does not possess", "rhou does not possess a", "does not possess a gtpase", "not possess a gtpase activity", "a gtpase activity saras", "gtpase activity saras et", "activity saras et al.", "al. 2004 . rhou has", "2004 . rhou has been", ". rhou has been reported", "rhou has been reported to", "has been reported to interact", "been reported to interact with", "reported to interact with some", "to interact with some gtpase", "interact with some gtpase activator", "with some gtpase activator proteins", "gtpase activator proteins gaps", "gaps bagci et", "al. 2020 which", "2020 which may", "which may serve as effectors", "may serve as effectors that", "serve as effectors that enable", "as effectors that enable cross", "effectors that enable cross talk", "that enable cross talk with", "enable cross talk with other", "cross talk with other rho", "talk with other rho gtpases.", "with other rho gtpases. rhou", "other rho gtpases. rhou was", "rho gtpases. rhou was shown", "gtpases. rhou was shown to", "rhou was shown to regulate", "was shown to regulate cytoskeletal", "shown to regulate cytoskeletal dynamics", "regulate cytoskeletal dynamics cell", "cytoskeletal dynamics cell migration", "dynamics cell migration and", "cell migration and adhesion. rhou", "migration and adhesion. rhou is", "and adhesion. rhou is expressed", "adhesion. rhou is expressed during", "rhou is expressed during embryonic", "is expressed during embryonic development", "expressed during embryonic development and", "during embryonic development and regulates", "embryonic development and regulates cardiac", "and regulates cardiac dickover", "regulates cardiac dickover et", "cardiac dickover et al.", "et al. 2014 and", "al. 2014 and intestinal", "and intestinal slaymi et", "intestinal slaymi et al.", "et al. 2019 development.", "al. 2019 development. rhou", "2019 development. rhou activates", "development. rhou activates jnk and", "rhou activates jnk and akt", "activates jnk and akt signaling", "jnk and akt signaling during", "and akt signaling during cell", "akt signaling during cell migration", "during cell migration chuang", "cell migration chuang et", "migration chuang et al.", "chuang et al. 2007 .
              for", "et al. 2007 .
              for review", "2007 .
              for review please", ".
              for review please refer", "review please refer to", "please refer to faure and", "refer to faure and fort", "to faure and fort 2015", "and fort 2015 and", "fort 2015 and hodge", "2015 and hodge and", "and hodge and ridley 2020." ] }, { "record_id": "GLY_000594_1_1910", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013423", "r hsa", "hsa 9013423", "r hsa 9013423" ] }, { "record_id": "GLY_000594_1_1910", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rac3 gtpase", "gtpase cycle", "rac3 gtpase cycle", "this pathway", "pathway catalogues", "catalogues rac3", "rac3 guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "gtpase activator", "activator proteins", "gdp dissociation", "dissociation inhibitors", "and rac3", "rac3 effectors.", "effectors. rac3", "rac3 is", "is highly", "highly similar", "similar to", "to rac1", "92% amino", "amino acid", "acid 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gtpase", "activator proteins gaps", "gaps gdp", "dissociation inhibitors gdis", "gdis and rac3", "and rac3 effectors. rac3", "rac3 effectors. rac3 is", "effectors. rac3 is highly", "rac3 is highly similar", "is highly similar to", "highly similar to rac1", "to rac1 92%", "rac1 92% amino", "92% amino acid sequence", "amino acid sequence identity", "identity but", "but it is expressed", "it is expressed in", "is expressed in fewer", "expressed in fewer tissues", "in fewer tissues than", "fewer tissues than rac1.", "tissues than rac1. rac3", "than rac1. rac3 orthologues", "rac1. rac3 orthologues only", "rac3 orthologues only exist", "orthologues only exist in", "only exist in vertebrates", "in vertebrates de", "vertebrates de curtis", "de curtis 2019 .", "curtis 2019 . rac3", "2019 . rac3 is", ". rac3 is highly", "rac3 is highly expressed", "is highly expressed in", "highly expressed in neurons", "expressed in neurons and", "in neurons and plays", "neurons and plays an", "and plays an important", "plays an important role", "an important role in", "important role in neuronal", "role in neuronal and", "in neuronal and brain", "neuronal and brain development", "brain development de", "development de curtis", "curtis 2014 de", "2014 de curtis", "2019 . rac3 mutations", ". rac3 mutations have", "rac3 mutations have been", "mutations have been reported", "have been reported in", "been reported in patients", "reported in patients with", "in patients with intellectual", "patients with intellectual disability", "with intellectual disability and", "intellectual disability and brain", "disability and brain malformations", "brain malformations de", "malformations de curtis", ". rac3 is frequently", "rac3 is frequently overexpressed", "is frequently overexpressed in", "frequently overexpressed in cancer", "overexpressed in cancer and", "in cancer and contributes", "cancer and contributes to", "and contributes to proliferation", "to proliferation migration", "proliferation migration and", "migration and invasiveness of", "and invasiveness of cancer", "invasiveness of cancer cells", "cancer cells de", "cells de curtis", "this pathway catalogues rac3 guanine", "pathway catalogues rac3 guanine nucleotide", "catalogues rac3 guanine nucleotide exchange", "rac3 guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "gefs gtpase activator", "gtpase activator proteins gaps", "gaps gdp dissociation", "gdp dissociation inhibitors gdis", "inhibitors gdis and", "gdis and rac3 effectors.", "and rac3 effectors. rac3 is", "rac3 effectors. rac3 is highly", "effectors. rac3 is highly similar", "rac3 is highly similar to", "is highly similar to rac1", "similar to rac1 92%", "to rac1 92% amino", "rac1 92% amino acid", "92% amino acid sequence identity", "sequence identity but", "identity but it", "but it is expressed in", "it is expressed in fewer", "is expressed in fewer tissues", "expressed in fewer tissues than", "in fewer tissues than rac1.", "fewer tissues than rac1. rac3", "tissues than rac1. rac3 orthologues", "than rac1. rac3 orthologues only", "rac1. rac3 orthologues only exist", "rac3 orthologues only exist in", "orthologues only exist in vertebrates", "exist in vertebrates de", "in vertebrates de curtis", "vertebrates de curtis 2019", "de curtis 2019 . rac3", "curtis 2019 . rac3 is", "2019 . rac3 is highly", ". rac3 is highly expressed", "rac3 is highly expressed in", "is highly expressed in neurons", "highly expressed in neurons and", "expressed in neurons and plays", "in neurons and plays an", "neurons and plays an important", "and plays an important role", "plays an important role in", "an important role in neuronal", "important role in neuronal and", "role in neuronal and brain", "in neuronal and brain development", "and brain development de", "brain development de curtis", "development de curtis 2014", "de curtis 2014 de", "curtis 2014 de curtis", "2014 de curtis 2019", "curtis 2019 . rac3 mutations", "2019 . rac3 mutations have", ". rac3 mutations have been", "rac3 mutations have been reported", "mutations have been reported in", "have been reported in patients", "been reported in patients with", "reported in patients with intellectual", "in patients with intellectual disability", "patients with intellectual disability and", "with intellectual disability and brain", "intellectual disability and brain malformations", "and brain malformations de", "brain malformations de curtis", "malformations de curtis 2019", "2019 . rac3 is frequently", ". rac3 is frequently overexpressed", "rac3 is frequently overexpressed in", "is frequently overexpressed in cancer", "frequently overexpressed in cancer and", "overexpressed in cancer and contributes", "in cancer and contributes to", "cancer and contributes to proliferation", "contributes to proliferation migration", "to proliferation migration and", "proliferation migration and invasiveness", "migration and invasiveness of cancer", "and invasiveness of cancer cells", "of cancer cells de", "cancer cells de curtis", "cells de curtis 2019" ] }, { "record_id": "GLY_000594_1_1911", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013424", "r hsa", "hsa 9013424", "r hsa 9013424" ] }, { "record_id": "GLY_000594_1_1911", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhov gtpase", "gtpase cycle", "rhov gtpase cycle", "also known", "known as", "as chp", "is an", "an atypical", "atypical rho", "rho gtpase", "gtpase that", "that is", "is thought", "thought to", "to be", "be constitutively", "constitutively active", "active due", "due to", "to its", "its high", "high intrinsic", "intrinsic guanine", "guanine nucleotide", "nucleotide exchange", "exchange activity.", "activity. no", "no guanine", "exchange factors", "nor gtpase", "gtpase activator", "activator proteins", "that act", "act on", "on rhov", "rhov have", "have been", "been identified.", "identified. rhov", "rhov is", "is expressed", "expressed at", "at very", "very low", "low levels.", "levels. the", "the expression", "expression of", "of rhov", "is detected", "detected during", "during embryonic", "embryonic development", "development in", "in fish", "tay et", "et al.", "al. 2010", "gu\u00e9mar et", "al. 2007", "and chicken", "notarnicola et", "al. 2008", "2008 .", ". rhov", "is involved", "involved in", "in neural", "neural crest", "crest formation", "where its", "its expression", "expression is", "is induced", "induced downstream", "downstream of", "of wnt", "wnt signaling.", "signaling. rhov", "to regulate", "regulate cell", "cell adhesion", "as its", "its zebrafish", "zebrafish orthologue", "orthologue is", "is required", "required for", "for proper", "proper localization", "localization of", "of e", "e cadherin", "cadherin and", "and beta", "beta catenin", "catenin at", "at adherens", "adherens junctions.", "junctions. rhov", "rhov activates", "activates jnk", "jnk and", "and induces", "induces apoptosis", "apoptosis in", "in rat", "rat pheochromocytoma", "pheochromocytoma cell", "cell line", "line pc12", "shepelev et", "et al", "al 2011", "and in", "in macrophages", "song et", "al. 2015", "2015 .

              rhov", ".

              rhov gene", "gene overexpression", "overexpression is", "is a", "a molecular", "molecular marker", "marker of", "of human", "human lung", "lung adenocarcinoma", "shepelev and", "and korobko", "korobko 2013", "shukla et", "al. 2017", "ma et", "al. 2020", "zhang et", "where rhov", "is likely", "likely to", "to act", "act as", "as an", "an oncogene", "chen et", "al. 2021", "2021 .

              for", ".

              for review", "please refer", "refer to", "to faure", "faure and", "and fort", "fort 2015", "and hodge", "hodge and", "and ridley", "ridley 2020.", "rhov also", "also known as", "known as chp", "chp is", "is an atypical", "an atypical rho", "atypical rho gtpase", "rho gtpase that", "gtpase that is", "that is thought", "is thought to", "thought to be", "to be constitutively", "be constitutively active", "constitutively active due", "active due to", "due to its", "to its high", "its high intrinsic", "high intrinsic guanine", "intrinsic guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange activity.", "exchange activity. no", "activity. no guanine", "no guanine nucleotide", "nucleotide exchange factors", "factors gefs", "gefs nor", "nor gtpase activator", "gtpase activator proteins", "proteins gaps", "gaps that", "that act on", "act on rhov", "on rhov have", "rhov have been", "have been identified.", "been identified. rhov", "identified. rhov is", "rhov is expressed", "is expressed at", "expressed at very", "at very low", "very low levels.", "low levels. the", "levels. the expression", "the expression of", "expression of rhov", "of rhov is", "rhov is detected", "is detected during", "detected during embryonic", "during embryonic development", "embryonic development in", "development in fish", "fish tay", "tay et al.", "et al. 2010", "frog gu\u00e9mar", "gu\u00e9mar et al.", "et al. 2007", "2007 and", "chicken notarnicola", "notarnicola et al.", "et al. 2008", "al. 2008 .", "2008 . rhov", ". rhov is", "rhov is involved", "is involved in", "involved in neural", "in neural crest", "neural crest formation", "formation where", "where its expression", "its expression is", "expression is induced", "is induced downstream", "induced downstream of", "downstream of wnt", "of wnt signaling.", "wnt signaling. rhov", "signaling. rhov is", "rhov is thought", "thought to regulate", "to regulate cell", "regulate cell adhesion", "adhesion as", "as its zebrafish", "its zebrafish orthologue", "zebrafish orthologue is", "orthologue is required", "is required for", "required for proper", "for proper localization", "proper localization of", "localization of e", "of e cadherin", "e cadherin and", "cadherin and beta", "and beta catenin", "beta catenin at", "catenin at adherens", "at adherens junctions.", "adherens junctions. rhov", "junctions. rhov activates", "rhov activates jnk", "activates jnk and", "jnk and induces", "and induces apoptosis", "induces apoptosis in", "apoptosis in rat", "in rat pheochromocytoma", "rat pheochromocytoma cell", "pheochromocytoma cell line", "cell line pc12", "pc12 shepelev", "shepelev et al", "et al 2011", "2011 and", "and in macrophages", "macrophages song", "song et al.", "et al. 2015", "al. 2015 .

              rhov", "2015 .

              rhov gene", ".

              rhov gene overexpression", "gene overexpression is", "overexpression is a", "is a molecular", "a molecular marker", "molecular marker of", "marker of human", "of human lung", "human lung adenocarcinoma", "adenocarcinoma shepelev", "shepelev and korobko", "and korobko 2013", "2013 shukla", "shukla et al.", "et al. 2017", "2017 ma", "ma et al.", "et al. 2020", "2020 zhang", "zhang et al.", "where rhov is", "rhov is likely", "is likely to", "likely to act", "to act as", "act as an", "as an oncogene", "oncogene chen", "chen et al.", "et al. 2021", "al. 2021 .

              for", "2021 .

              for review", "review please", "please refer to", "refer to faure", "to faure and", "faure and fort", "and fort 2015", "2015 and", "and hodge and", "hodge and ridley", "and ridley 2020.", "rhov also known", "also known as chp", "as chp is", "chp is an", "is an atypical rho", "an atypical rho gtpase", "atypical rho gtpase that", "rho gtpase that is", "gtpase that is thought", "that is thought to", "is thought to be", "thought to be constitutively", "to be constitutively active", "be constitutively active due", "constitutively active due to", "active due to its", "due to its high", "to its high intrinsic", "its high intrinsic guanine", "high intrinsic guanine nucleotide", "intrinsic guanine nucleotide exchange", "guanine nucleotide exchange activity.", "nucleotide exchange activity. no", "exchange activity. no guanine", "activity. no guanine nucleotide", "no guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs nor gtpase", "nor gtpase activator proteins", "activator proteins gaps", "gaps that act", "that act on rhov", "act on rhov have", "on rhov have been", "rhov have been identified.", "have been identified. rhov", "been identified. rhov is", "identified. rhov is expressed", "rhov is expressed at", "is expressed at very", "expressed at very low", "at very low levels.", "very low levels. the", "low levels. the expression", "levels. the expression of", "the expression of rhov", "expression of rhov is", "of rhov is detected", "rhov is detected during", "is detected during embryonic", "detected during embryonic development", "during embryonic development in", "embryonic development in fish", "in fish tay", "fish tay et", "tay et al. 2010", "2010 frog", "frog gu\u00e9mar et", "gu\u00e9mar et al. 2007", "al. 2007 and", "2007 and chicken", "and chicken notarnicola", "chicken notarnicola et", "notarnicola et al. 2008", "et al. 2008 .", "al. 2008 . rhov", "2008 . rhov is", ". rhov is involved", "rhov is involved in", "is involved in neural", "involved in neural crest", "in neural crest formation", "crest formation where", "formation where its", "where its expression is", "its expression is induced", "expression is induced downstream", "is induced downstream of", "induced downstream of wnt", "downstream of wnt signaling.", "of wnt signaling. rhov", "wnt signaling. rhov is", "signaling. rhov is thought", "rhov is thought to", "is thought to regulate", "thought to regulate cell", "to regulate cell adhesion", "cell adhesion as", "adhesion as its", "as its zebrafish orthologue", "its zebrafish orthologue is", "zebrafish orthologue is required", "orthologue is required for", "is required for proper", "required for proper localization", "for proper localization of", "proper localization of e", "localization of e cadherin", "of e cadherin and", "e cadherin and beta", "cadherin and beta catenin", "and beta catenin at", "beta catenin at adherens", "catenin at adherens junctions.", "at adherens junctions. rhov", "adherens junctions. rhov activates", "junctions. rhov activates jnk", "rhov activates jnk and", "activates jnk and induces", "jnk and induces apoptosis", "and induces apoptosis in", "induces apoptosis in rat", "apoptosis in rat pheochromocytoma", "in rat pheochromocytoma cell", "rat pheochromocytoma cell line", "pheochromocytoma cell line pc12", "line pc12 shepelev", "pc12 shepelev et", "shepelev et al 2011", "al 2011 and", "2011 and in", "in macrophages song", "macrophages song et", "song et al. 2015", "et al. 2015 .

              rhov", "al. 2015 .

              rhov gene", "2015 .

              rhov gene overexpression", ".

              rhov gene overexpression is", "gene overexpression is a", "overexpression is a molecular", "is a molecular marker", "a molecular marker of", "molecular marker of human", "marker of human lung", "of human lung adenocarcinoma", "lung adenocarcinoma shepelev", "adenocarcinoma shepelev and", "shepelev and korobko 2013", "korobko 2013 shukla", "2013 shukla et", "shukla et al. 2017", "al. 2017 ma", "2017 ma et", "ma et al. 2020", "al. 2020 zhang", "2020 zhang et", "zhang et al. 2020", "2020 where", "where rhov is likely", "rhov is likely to", "is likely to act", "likely to act as", "to act as an", "act as an oncogene", "an oncogene chen", "oncogene chen et", "chen et al. 2021", "et al. 2021 .

              for", "al. 2021 .

              for review", ".

              for review please", "review please refer", "please refer to faure", "refer to faure and", "to faure and fort", "faure and fort 2015", "fort 2015 and", "2015 and hodge", "and hodge and ridley", "hodge and ridley 2020.", "rhov also known as", "known as chp is", "as chp is an", "chp is an atypical", "is an atypical rho gtpase", "an atypical rho gtpase that", "atypical rho gtpase that is", "rho gtpase that is thought", "gtpase that is thought to", "that is thought to be", "is thought to be constitutively", "thought to be constitutively active", "to be constitutively active due", "be constitutively active due to", "constitutively active due to its", "active due to its high", "due to its high intrinsic", "to its high intrinsic guanine", "its high intrinsic guanine nucleotide", "high intrinsic guanine nucleotide exchange", "intrinsic guanine nucleotide exchange activity.", "guanine nucleotide exchange activity. no", "nucleotide exchange activity. no guanine", "exchange activity. no guanine nucleotide", "activity. no guanine nucleotide exchange", "no guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "factors gefs nor", "gefs nor gtpase activator", "gtpase activator proteins gaps", "proteins gaps that", "gaps that act on", "that act on rhov have", "act on rhov have been", "on rhov have been identified.", "rhov have been identified. rhov", "have been identified. rhov is", "been identified. rhov is expressed", "identified. rhov is expressed at", "rhov is expressed at very", "is expressed at very low", "expressed at very low levels.", "at very low levels. the", "very low levels. the expression", "low levels. the expression of", "levels. the expression of rhov", "the expression of rhov is", "expression of rhov is detected", "of rhov is detected during", "rhov is detected during embryonic", "is detected during embryonic development", "detected during embryonic development in", "during embryonic development in fish", "development in fish tay", "in fish tay et", "fish tay et al.", "al. 2010 frog", "frog gu\u00e9mar et al.", "et al. 2007 and", "al. 2007 and chicken", "and chicken notarnicola et", "chicken notarnicola et al.", "notarnicola et al. 2008 .", "et al. 2008 . rhov", "al. 2008 . rhov is", "2008 . rhov is involved", ". rhov is involved in", "rhov is involved in neural", "is involved in neural crest", "involved in neural crest formation", "neural crest formation where", "crest formation where its", "formation where its expression", "where its expression is induced", "its expression is induced downstream", "expression is induced downstream of", "is induced downstream of wnt", "induced downstream of wnt signaling.", "downstream of wnt signaling. rhov", "of wnt signaling. rhov is", "wnt signaling. rhov is thought", "signaling. rhov is thought to", "rhov is thought to regulate", "is thought to regulate cell", "thought to regulate cell adhesion", "regulate cell adhesion as", "cell adhesion as its", "adhesion as its zebrafish", "as its zebrafish orthologue is", "its zebrafish orthologue is required", "zebrafish orthologue is required for", "orthologue is required for proper", "is required for proper localization", "required for proper localization of", "for proper localization of e", "proper localization of e cadherin", "localization of e cadherin and", "of e cadherin and beta", "e cadherin and beta catenin", "cadherin and beta catenin at", "and beta catenin at adherens", "beta catenin at adherens junctions.", "catenin at adherens junctions. rhov", "at adherens junctions. rhov activates", "adherens junctions. rhov activates jnk", "junctions. rhov activates jnk and", "rhov activates jnk and induces", "activates jnk and induces apoptosis", "jnk and induces apoptosis in", "and induces apoptosis in rat", "induces apoptosis in rat pheochromocytoma", "apoptosis in rat pheochromocytoma cell", "in rat pheochromocytoma cell line", "rat pheochromocytoma cell line pc12", "cell line pc12 shepelev", "line pc12 shepelev et", "pc12 shepelev et al", "et al 2011 and", "al 2011 and in", "2011 and in macrophages", "and in macrophages song", "in macrophages song et", "macrophages song et al.", "song et al. 2015 .

              rhov", "et al. 2015 .

              rhov gene", "al. 2015 .

              rhov gene overexpression", "2015 .

              rhov gene overexpression is", ".

              rhov gene overexpression is a", "gene overexpression is a molecular", "overexpression is a molecular marker", "is a molecular marker of", "a molecular marker of human", "molecular marker of human lung", "marker of human lung adenocarcinoma", "human lung adenocarcinoma shepelev", "lung adenocarcinoma shepelev and", "adenocarcinoma shepelev and korobko", "and korobko 2013 shukla", "korobko 2013 shukla et", "2013 shukla et al.", "et al. 2017 ma", "al. 2017 ma et", "2017 ma et al.", "et al. 2020 zhang", "al. 2020 zhang et", "2020 zhang et al.", "al. 2020 where", "2020 where rhov", "where rhov is likely to", "rhov is likely to act", "is likely to act as", "likely to act as an", "to act as an oncogene", "as an oncogene chen", "an oncogene chen et", "oncogene chen et al.", "chen et al. 2021 .

              for", "et al. 2021 .

              for review", "2021 .

              for review please", ".

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              ribbon synapses", "synapses are", "are characterized", "characterized by", "a multiprotein", "multiprotein complex", "the ribbon", "that contains", "least bassoon", "an isoform", "isoform of", "of ctbp2", "and piccolino", "a small", "small isoform", "of piccolo", "and appears", "appears to", "to act", "act to", "to transiently", "transiently tether", "tether vesicles", "vesicles near", "near the", "synapse and", "and thereby", "thereby increase", "increase the", "the pool", "pool of", "of readily", "readily releasable", "releasable vesicles", "in safieddine", "safieddine et", "et al.", "al. 2012", "wichman and", "moser 2015", "pangrsic and", "vogl 2018", "moser et", "al. 2020", "2020 .
              atp2b1", ".
              atp2b1 calcium", "calcium channels", "atp2b2 calcium", "kcnma1:kcnmb1:lrrc52 potassium", "potassium channels", "and basolateral", "basolateral kcnq4", "kcnq4 potassium", "channels transport", "transport cations", "cations out", "out of", "thereby act", "to repolarize", "repolarize the", "cell and", "and limit", "limit the", "the duration", "duration of", "the synaptic", "synaptic potentials", "in patuzzi", "patuzzi 2011", "oak and", "and yi", "yi 2014", "2014 .", "cells ihcs", "ihcs of", "the cochlea transduce", "cochlea transduce sound", "transduce sound waves", "sound waves into", "waves into an", "into an ionic", "ionic mainly", "potassium current", "current that leads", "that leads to", "leads to exocytosis", "to exocytosis of", "exocytosis of glutamate", "of glutamate from", "glutamate from the", "from the ihc", "the ihc and", "ihc and activation", "and activation of", "activation of postsynaptic", "of postsynaptic type", "postsynaptic type i", "type i afferent", "i afferent fibers", "afferent fibers of", "fibers of the", "of the radial", "the radial ganglion", "ganglion reviewed", "reviewed in meyer", "in meyer and", "meyer and moser", "and moser 2010", "2010 moser", "moser and vogl", "and vogl 2016", "2016 fettiplace", "fettiplace 2017 .", "2017 . ihcs", ". ihcs have", "ihcs have stereocilia", "have stereocilia on", "stereocilia on their", "on their apical", "their apical surface", "apical surface that", "surface that are", "that are arranged", "are arranged in", "arranged in rows", "in rows of", "rows of increasing", "of increasing height", "height a", "a \\staircase\\ arrangement.", "\\staircase\\ arrangement. stereocilia", "arrangement. stereocilia of", "stereocilia of different", "of different rows", "different rows are", "rows are connected", "are connected by", "connected by a", "by a tip", "a tip link", "tip link comprising", "link comprising a", "comprising a cdh23", "a cdh23 dimer", "cdh23 dimer on", "dimer on the", "on the taller", "the taller stereocilium", "taller stereocilium bound", "stereocilium bound to", "bound to a", "to a pcdh15", "a pcdh15 dimer", "pcdh15 dimer on", "on the shorter", "the shorter stereocilium.", "shorter stereocilium. pcdh15", "stereocilium. pcdh15 interacts", "pcdh15 interacts with", "interacts with lhfpl5", "lhfpl5 an", "an auxiliary subunit", "auxiliary subunit of", "subunit of the", "of the mechanoelectrical", "the mechanoelectrical transduction", "mechanoelectrical transduction channel", "channel met", "channel also", "also called the", "called the mechanotransduction", "the mechanotransduction channel", "which contains at", "contains at least", "at least tmc1", "tmc1 adults", "adults or", "tmc2 newborns", "tmie and", "and the auxiliary", "the auxiliary subunits", "auxiliary subunits lhfpl5", "subunits lhfpl5 and", "lhfpl5 and cib2", "cib2 reviewed", "reviewed in fettiplace", "in fettiplace and", "fettiplace and kim", "and kim 2014", "2014 fettiplace", "fettiplace 2016 .
              deflection", "2016 .
              deflection of", ".
              deflection of the", "of the stereocilia", "the stereocilia by", "stereocilia by sound", "by sound waves", "sound waves creates", "waves creates tension", "creates tension on", "tension on the", "on the tip", "the tip link", "tip link that", "link that increases", "that increases the", "increases the open", "the open probability", "open probability of", "probability of the", "of the met", "the met channel", "channel which", "which then transports", "then transports calcium", "transports calcium and", "calcium and potassium", "and potassium ions", "potassium ions from", "ions from the", "from the scala", "the scala media", "scala media into", "media into the", "into the ihc", "ihc depolarizing", "depolarizing the ihc", "ihc reviewed", "in fettiplace 2017", "2017 . the", ". the potassium", "the potassium channel", "potassium channel kcnq4", "channel kcnq4 located", "kcnq4 located in", "located in the", "in the neck", "the neck region", "neck region of", "region of the", "of the cell", "the cell may", "cell may also", "may also participate", "also participate in", "participate in depolarization.", "in depolarization. the", "depolarization. the depolarization", "the depolarization of", "depolarization of the", "of the ihc", "the ihc opens", "ihc opens voltage", "opens voltage gated", "voltage gated cav1.3", "gated cav1.3 channels", "channels cacna1d:caca2d2:cacnb2", "cacna1d:caca2d2:cacnb2 located", "located in stripes", "in stripes near", "stripes near ribbon", "near ribbon synapses", "ribbon synapses on", "synapses on the", "on the basolateral", "the basolateral surface", "basolateral surface of", "surface of the", "of the ihc.", "the ihc. the", "ihc. the resulting", "the resulting localized", "resulting localized influx", "localized influx of", "influx of calcium", "of calcium ions", "calcium ions activates", "ions activates exocytosis", "activates exocytosis of", "of glutamate into", "glutamate into the", "into the synapse", "the synapse by", "synapse by an", "by an interaction", "an interaction between", "interaction between calcium", "between calcium and", "calcium and otoferlin", "otoferlin otof", "otof on", "on glutamate loaded", "glutamate loaded vesicles", "loaded vesicles in", "vesicles in the", "in the ihc", "reviewed in wichmann", "in wichmann 2015", "wichmann 2015 .
              ribbon", "2015 .
              ribbon synapses", ".
              ribbon synapses are", "synapses are characterized", "are characterized by", "characterized by a", "by a multiprotein", "a multiprotein complex", "complex the", "ribbon that", "that contains at", "at least bassoon", "bassoon ribeye", "ribeye an", "an isoform of", "isoform of ctbp2", "piccolino a", "a small isoform", "small isoform of", "isoform of piccolo", "piccolo and", "and appears to", "appears to act", "to act to", "act to transiently", "to transiently tether", "transiently tether vesicles", "tether vesicles near", "vesicles near the", "near the synapse", "the synapse and", "synapse and thereby", "and thereby increase", "thereby increase the", "increase the pool", "the pool of", "pool of readily", "of readily releasable", "readily releasable vesicles", "vesicles reviewed", "reviewed in safieddine", "in safieddine et", "safieddine et al.", "et al. 2012", "2012 wichman", "wichman and moser", "and moser 2015", "2015 pangrsic", "pangrsic and vogl", "and vogl 2018", "2018 moser", "moser et al.", "et al. 2020", "al. 2020 .
              atp2b1", "2020 .
              atp2b1 calcium", ".
              atp2b1 calcium channels", "channels atp2b2", "atp2b2 calcium channels", "channels kcnma1:kcnmb1:lrrc52", "kcnma1:kcnmb1:lrrc52 potassium channels", "channels and", "and basolateral kcnq4", "basolateral kcnq4 potassium", "kcnq4 potassium channels", "potassium channels transport", "channels transport cations", "transport cations out", "cations out of", "out of the", "ihc and thereby", "and thereby act", "thereby act to", "act to repolarize", "to repolarize the", "repolarize the cell", "the cell and", "cell and limit", "and limit the", "limit the duration", "the duration of", "duration of the", "of the synaptic", "the synaptic potentials", "potentials reviewed", "reviewed in patuzzi", "in patuzzi 2011", "2011 oak", "oak and yi", "and yi 2014", "yi 2014 .", "hair cells ihcs", "ihcs of the", "of the cochlea transduce", "the cochlea transduce sound", "cochlea transduce sound waves", "transduce sound waves into", "sound waves into an", "waves into an ionic", "an ionic mainly", "ionic mainly potassium", "mainly potassium current", "potassium current that", "current that leads to", "that leads to exocytosis", "leads to exocytosis of", "to exocytosis of glutamate", "exocytosis of glutamate from", "of glutamate from the", "glutamate from the ihc", "from the ihc and", "the ihc and activation", "ihc and activation of", "and activation of postsynaptic", "activation of postsynaptic type", "of postsynaptic type i", "postsynaptic type i afferent", "type i afferent fibers", "i afferent fibers of", "afferent fibers of the", "fibers of the radial", "of the radial ganglion", "radial ganglion reviewed", "ganglion reviewed in", "reviewed in meyer and", "in meyer and moser", "meyer and moser 2010", "moser 2010 moser", "2010 moser and", "moser and vogl 2016", "vogl 2016 fettiplace", "2016 fettiplace 2017", "fettiplace 2017 . ihcs", "2017 . ihcs have", ". ihcs have stereocilia", "ihcs have stereocilia on", "have stereocilia on their", "stereocilia on their apical", "on their apical surface", "their apical surface that", "apical surface that are", "surface that are arranged", "that are arranged in", "are arranged in rows", "arranged in rows of", "in rows of increasing", "rows of increasing height", "increasing height a", "height a \\staircase\\", "a \\staircase\\ arrangement. stereocilia", "\\staircase\\ arrangement. stereocilia of", "arrangement. stereocilia of different", "stereocilia of different rows", "of different rows are", "different rows are connected", "rows are connected by", "are connected by a", "connected by a tip", "by a tip link", "a tip link comprising", "tip link comprising a", "link comprising a cdh23", "comprising a cdh23 dimer", "a cdh23 dimer on", "cdh23 dimer on the", "dimer on the taller", "on the taller stereocilium", "the taller stereocilium bound", "taller stereocilium bound to", "stereocilium bound to a", "bound to a pcdh15", "to a pcdh15 dimer", "a pcdh15 dimer on", "pcdh15 dimer on the", "dimer on the shorter", "on the shorter stereocilium.", "the shorter stereocilium. pcdh15", "shorter stereocilium. pcdh15 interacts", "stereocilium. pcdh15 interacts with", "pcdh15 interacts with lhfpl5", "with lhfpl5 an", "lhfpl5 an auxiliary", "an auxiliary subunit of", "auxiliary subunit of the", "subunit of the mechanoelectrical", "of the mechanoelectrical transduction", "the mechanoelectrical transduction channel", "transduction channel met", "channel met channel", "met channel also", "channel also called", "also called the mechanotransduction", "called the mechanotransduction channel", "which contains at least", "contains at least tmc1", "least tmc1 adults", "adults or tmc2", "or tmc2 newborns", "newborns tmie", "tmie and the", "and the auxiliary subunits", "the auxiliary subunits lhfpl5", "auxiliary subunits lhfpl5 and", "subunits lhfpl5 and cib2", "and cib2 reviewed", "cib2 reviewed in", "reviewed in fettiplace and", "in fettiplace and kim", "fettiplace and kim 2014", "kim 2014 fettiplace", "2014 fettiplace 2016", "fettiplace 2016 .
              deflection of", "2016 .
              deflection of the", ".
              deflection of the stereocilia", "of the stereocilia by", "the stereocilia by sound", "stereocilia by sound waves", "by sound waves creates", "sound waves creates tension", "waves creates tension on", "creates tension on the", "tension on the tip", "on the tip link", "the tip link that", "tip link that increases", "link that increases the", "that increases the open", "increases the open probability", "the open probability of", "open probability of the", "probability of the met", "of the met channel", "met channel which", "channel which then", "which then transports calcium", "then transports calcium and", "transports calcium and potassium", "calcium and potassium ions", "and potassium ions from", "potassium ions from the", "ions from the scala", "from the scala media", "the scala media into", "scala media into the", "media into the ihc", "the ihc depolarizing", "ihc depolarizing the", "the ihc reviewed", "ihc reviewed in", "reviewed in fettiplace 2017", "in fettiplace 2017 .", "fettiplace 2017 . the", "2017 . the potassium", ". the potassium channel", "the potassium channel kcnq4", "potassium channel kcnq4 located", "channel kcnq4 located in", "kcnq4 located in the", "located in the neck", "in the neck region", "the neck region of", "neck region of the", "region of the cell", "of the cell may", "the cell may also", "cell may also participate", "may also participate in", "also participate in depolarization.", "participate in depolarization. the", "in depolarization. the depolarization", "depolarization. the depolarization of", "the depolarization of the", "depolarization of the ihc", "of the ihc opens", "the ihc opens voltage", "ihc opens voltage gated", "opens voltage gated cav1.3", "voltage gated cav1.3 channels", "cav1.3 channels cacna1d:caca2d2:cacnb2", "cacna1d:caca2d2:cacnb2 located in", "located in stripes near", "in stripes near ribbon", "stripes near ribbon synapses", "near ribbon synapses on", "ribbon synapses on the", "synapses on the basolateral", "on the basolateral surface", "the basolateral surface of", "basolateral surface of the", "surface of the ihc.", "of the ihc. the", "the ihc. the resulting", "ihc. the resulting localized", "the resulting localized influx", "resulting localized influx of", "localized influx of calcium", "influx of calcium ions", "of calcium ions activates", "calcium ions activates exocytosis", "ions activates exocytosis of", "activates exocytosis of glutamate", "exocytosis of glutamate into", "of glutamate into the", "glutamate into the synapse", "into the synapse by", "the synapse by an", "synapse by an interaction", "by an interaction between", "an interaction between calcium", "interaction between calcium and", "between calcium and otoferlin", "and otoferlin otof", "otof on glutamate", "on glutamate loaded vesicles", "glutamate loaded vesicles in", "loaded vesicles in the", "vesicles in the ihc", "reviewed in wichmann 2015", "in wichmann 2015 .
              ribbon", "wichmann 2015 .
              ribbon synapses", "2015 .
              ribbon synapses are", ".
              ribbon synapses are characterized", "synapses are characterized by", "are characterized by a", "characterized by a multiprotein", "by a multiprotein complex", "multiprotein complex the", "complex the ribbon", "the ribbon that", "ribbon that contains", "that contains at least", "contains at least bassoon", "least bassoon ribeye", "ribeye an isoform", "an isoform of ctbp2", "ctbp2 and", "and piccolino a", "piccolino a small", "a small isoform of", "small isoform of piccolo", "of piccolo and", "piccolo and appears", "and appears to act", "appears to act to", "to act to transiently", "act to transiently tether", "to transiently tether vesicles", "transiently tether vesicles near", "tether vesicles near the", "vesicles near the synapse", "near the synapse and", "the synapse and thereby", "synapse and thereby increase", "and thereby increase the", "thereby increase the pool", "increase the pool of", "the pool of readily", "pool of readily releasable", "of readily releasable vesicles", "releasable vesicles reviewed", "vesicles reviewed in", "reviewed in safieddine et", "in safieddine et al.", "safieddine et al. 2012", "al. 2012 wichman", "2012 wichman and", "wichman and moser 2015", "moser 2015 pangrsic", "2015 pangrsic and", "pangrsic and vogl 2018", "vogl 2018 moser", "2018 moser et", "moser et al. 2020", "et al. 2020 .
              atp2b1", "al. 2020 .
              atp2b1 calcium", "2020 .
              atp2b1 calcium channels", "calcium channels atp2b2", "channels atp2b2 calcium", "calcium channels kcnma1:kcnmb1:lrrc52", "channels kcnma1:kcnmb1:lrrc52 potassium", "potassium channels and", "channels and basolateral", "and basolateral kcnq4 potassium", "basolateral kcnq4 potassium channels", "kcnq4 potassium channels transport", "potassium channels transport cations", "channels transport cations out", "transport cations out of", "cations out of the", "out of the ihc", "of the ihc and", "the ihc and thereby", "ihc and thereby act", "and thereby act to", "thereby act to repolarize", "act to repolarize the", "to repolarize the cell", "repolarize the cell and", "the cell and limit", "cell and limit the", "and limit the duration", "limit the duration of", "the duration of the", "duration of the synaptic", "of the synaptic potentials", "synaptic potentials reviewed", "potentials reviewed in", "reviewed in patuzzi 2011", "patuzzi 2011 oak", "2011 oak and", "oak and yi 2014", "and yi 2014 .", "inner hair cells ihcs", "cells ihcs of", "ihcs of the cochlea", "of the cochlea transduce sound", "the cochlea transduce sound waves", "cochlea transduce sound waves into", "transduce sound waves into an", "sound waves into an ionic", "into an ionic mainly", "an ionic mainly potassium", "mainly potassium current that", "potassium current that leads", "current that leads to exocytosis", "that leads to exocytosis of", "leads to exocytosis of glutamate", "to exocytosis of glutamate from", "exocytosis of glutamate from the", "of glutamate from the ihc", "glutamate from the ihc and", "from the ihc and activation", "the ihc and activation of", "ihc and activation of postsynaptic", "and activation of postsynaptic type", "activation of postsynaptic type i", "of postsynaptic type i afferent", "postsynaptic type i afferent fibers", "type i afferent fibers of", "i afferent fibers of the", "afferent fibers of the radial", "fibers of the radial ganglion", "the radial ganglion reviewed", "radial ganglion reviewed in", "ganglion reviewed in meyer", "reviewed in meyer and moser", "in meyer and moser 2010", "and moser 2010 moser", "moser 2010 moser and", "2010 moser and vogl", "and vogl 2016 fettiplace", "vogl 2016 fettiplace 2017", "2016 fettiplace 2017 .", "fettiplace 2017 . ihcs have", "2017 . ihcs have stereocilia", ". ihcs have stereocilia on", "ihcs have stereocilia on their", "have stereocilia on their apical", "stereocilia on their apical surface", "on their apical surface that", "their apical surface that are", "apical surface that are arranged", "surface that are arranged in", "that are arranged in rows", "are arranged in rows of", "arranged in rows of increasing", "in rows of increasing height", "of increasing height a", "increasing height a \\staircase\\", "height a \\staircase\\ arrangement.", "a \\staircase\\ arrangement. stereocilia of", "\\staircase\\ arrangement. stereocilia of different", "arrangement. stereocilia of different rows", "stereocilia of different rows are", "of different rows are connected", "different rows are connected by", "rows are connected by a", "are connected by a tip", "connected by a tip link", "by a tip link comprising", "a tip link comprising a", "tip link comprising a cdh23", "link comprising a cdh23 dimer", "comprising a cdh23 dimer on", "a cdh23 dimer on the", "cdh23 dimer on the taller", "dimer on the taller stereocilium", "on the taller stereocilium bound", "the taller stereocilium bound to", "taller stereocilium bound to a", "stereocilium bound to a pcdh15", "bound to a pcdh15 dimer", "to a pcdh15 dimer on", "a pcdh15 dimer on the", "pcdh15 dimer on the shorter", "dimer on the shorter stereocilium.", "on the shorter stereocilium. pcdh15", "the shorter stereocilium. pcdh15 interacts", "shorter stereocilium. pcdh15 interacts with", "stereocilium. pcdh15 interacts with lhfpl5", "interacts with lhfpl5 an", "with lhfpl5 an auxiliary", "lhfpl5 an auxiliary subunit", "an auxiliary subunit of the", "auxiliary subunit of the mechanoelectrical", "subunit of the mechanoelectrical transduction", "of the mechanoelectrical transduction channel", "mechanoelectrical transduction channel met", "transduction channel met channel", "met channel also called", "channel also called the", "also called the mechanotransduction channel", "mechanotransduction channel which", "channel which contains", "which contains at least tmc1", "at least tmc1 adults", "tmc1 adults or", "tmie and the auxiliary", "and the auxiliary subunits lhfpl5", "the auxiliary subunits lhfpl5 and", "auxiliary subunits lhfpl5 and cib2", "lhfpl5 and cib2 reviewed", "and cib2 reviewed in", "cib2 reviewed in fettiplace", "reviewed in fettiplace and kim", "in fettiplace and kim 2014", "and kim 2014 fettiplace", "kim 2014 fettiplace 2016", "2014 fettiplace 2016 .
              deflection", "fettiplace 2016 .
              deflection of the", "2016 .
              deflection of the stereocilia", ".
              deflection of the stereocilia by", "of the stereocilia by sound", "the stereocilia by sound waves", "stereocilia by sound waves creates", "by sound waves creates tension", "sound waves creates tension on", "waves creates tension on the", "creates tension on the tip", "tension on the tip link", "on the tip link that", "the tip link that increases", "tip link that increases the", "link that increases the open", "that increases the open probability", "increases the open probability of", "the open probability of the", "open probability of the met", "probability of the met channel", "the met channel which", "met channel which then", "channel which then transports", "which then transports calcium and", "then transports calcium and potassium", "transports calcium and potassium ions", "calcium and potassium ions from", "and potassium ions from the", "potassium ions from the scala", "ions from the scala media", "from the scala media into", "the scala media into the", "scala media into the ihc", "into the ihc depolarizing", "the ihc depolarizing the", "ihc depolarizing the ihc", "depolarizing the ihc reviewed", "the ihc reviewed in", "ihc reviewed in fettiplace", "reviewed in fettiplace 2017 .", "in fettiplace 2017 . the", "fettiplace 2017 . the potassium", "2017 . the potassium channel", ". the potassium channel kcnq4", "the potassium channel kcnq4 located", "potassium channel kcnq4 located in", "channel kcnq4 located in the", "kcnq4 located in the neck", "located in the neck region", "in the neck region of", "the neck region of the", "neck region of the cell", "region of the cell may", "of the cell may also", "the cell may also participate", "cell may also participate in", "may also participate in depolarization.", "also participate in depolarization. the", "participate in depolarization. the depolarization", "in depolarization. the depolarization of", "depolarization. the depolarization of the", "the depolarization of the ihc", "depolarization of the ihc opens", "of the ihc opens voltage", "the ihc opens voltage gated", "ihc opens voltage gated cav1.3", "opens voltage gated cav1.3 channels", "gated cav1.3 channels cacna1d:caca2d2:cacnb2", "channels cacna1d:caca2d2:cacnb2 located", "cacna1d:caca2d2:cacnb2 located in stripes", "located in stripes near ribbon", "in stripes near ribbon synapses", "stripes near ribbon synapses on", "near ribbon synapses on the", "ribbon synapses on the basolateral", "synapses on the basolateral surface", "on the basolateral surface of", "the basolateral surface of the", "basolateral surface of the ihc.", "surface of the ihc. the", "of the ihc. the resulting", "the ihc. the resulting localized", "ihc. the resulting localized influx", "the resulting localized influx of", "resulting localized influx of calcium", "localized influx of calcium ions", "influx of calcium ions activates", "of calcium ions activates exocytosis", "calcium ions activates exocytosis of", "ions activates exocytosis of glutamate", "activates exocytosis of glutamate into", "exocytosis of glutamate into the", "of glutamate into the synapse", "glutamate into the synapse by", "into the synapse by an", "the synapse by an interaction", "synapse by an interaction between", "by an interaction between calcium", "an interaction between calcium and", "interaction between calcium and otoferlin", "calcium and otoferlin otof", "otoferlin otof on", "otof on glutamate loaded", "on glutamate loaded vesicles in", "glutamate loaded vesicles in the", "loaded vesicles in the ihc", "in the ihc reviewed", "ihc reviewed in wichmann", "reviewed in wichmann 2015 .
              ribbon", "in wichmann 2015 .
              ribbon synapses", "wichmann 2015 .
              ribbon synapses are", "2015 .
              ribbon synapses are characterized", ".
              ribbon synapses are characterized by", "synapses are characterized by a", "are characterized by a multiprotein", "characterized by a multiprotein complex", "a multiprotein complex the", "multiprotein complex the ribbon", "the ribbon that contains", "ribbon that contains at", "that contains at least bassoon", "at least bassoon ribeye", "bassoon ribeye an", "ribeye an isoform of", "of ctbp2 and", "ctbp2 and piccolino", "and piccolino a small", "piccolino a small isoform", "a small isoform of piccolo", "isoform of piccolo and", "of piccolo and appears", "piccolo and appears to", "and appears to act to", "appears to act to transiently", "to act to transiently tether", "act to transiently tether vesicles", "to transiently tether vesicles near", "transiently tether vesicles near the", "tether vesicles near the synapse", "vesicles near the synapse and", "near the synapse and thereby", "the synapse and thereby increase", "synapse and thereby increase the", "and thereby increase the pool", "thereby increase the pool of", "increase the pool of readily", "the pool of readily releasable", "pool of readily releasable vesicles", "readily releasable vesicles reviewed", "releasable vesicles reviewed in", "vesicles reviewed in safieddine", "reviewed in safieddine et al.", "in safieddine et al. 2012", "et al. 2012 wichman", "al. 2012 wichman and", "2012 wichman and moser", "and moser 2015 pangrsic", "moser 2015 pangrsic and", "2015 pangrsic and vogl", "and vogl 2018 moser", "vogl 2018 moser et", "2018 moser et al.", "moser et al. 2020 .
              atp2b1", "et al. 2020 .
              atp2b1 calcium", "al. 2020 .
              atp2b1 calcium channels", ".
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height.", "rows of ascending height. a", "of ascending height. a taller", "ascending height. a taller stereocilium", "height. a taller stereocilium is", "a taller stereocilium is connected", "taller stereocilium is connected to", "stereocilium is connected to a", "is connected to a shorter", "connected to a shorter stereocilium", "to a shorter stereocilium by", "a shorter stereocilium by a", "shorter stereocilium by a tip", "stereocilium by a tip link", "by a tip link comprising", "a tip link comprising a", "tip link comprising a cdh23", "link comprising a cdh23 dimer", "comprising a cdh23 dimer onthe", "a cdh23 dimer onthe side", "cdh23 dimer onthe side of", "dimer onthe side of the", "onthe side of the taller", "side of the taller stereocilium", "of the taller stereocilium and", "the taller stereocilium and a", "taller stereocilium and a pcdh15", "stereocilium and a pcdh15 dimer", "and a pcdh15 dimer on", "a pcdh15 dimer on theapex", "pcdh15 dimer on theapex of", "dimer on theapex of the", "on theapex of the shorter", "theapex of the shorter stereocilium.", "of the shorter stereocilium. pcdh15", "the shorter stereocilium. pcdh15 interacts", "shorter stereocilium. pcdh15 interacts with", "stereocilium. pcdh15 interacts with lhfpl5", "interacts with lhfpl5 a", "with lhfpl5 a subunit", "lhfpl5 a subunit of", "a subunit of the mechanoelectrical", "subunit of the mechanoelectrical transduction", "of the mechanoelectrical transduction channel", "the mechanoelectrical transduction channel complex", "transduction channel complex met", "channel complex met channel", "met channel also called", "channel also called the", "also called the mechanotransduction channel", "mechanotransduction channel which", "channel which contains", "which contains tmc1 or tmc2", "tmc1 or tmc2 tmie", "tmc2 tmie cib2", "tmie cib2 and", "and lhfpl5 reviewed in", "lhfpl5 reviewed in fettiplace", "reviewed in fettiplace 2016 .", "in fettiplace 2016 . deflection", "fettiplace 2016 . deflection of", "2016 . deflection of the", ". deflection of the stereocilia", "deflection of the stereocilia in", "of the stereocilia in one", "the stereocilia in one direction", "stereocilia in one direction produces", "in one direction produces tension", "one direction produces tension on", "direction produces tension on the", "produces tension on the tip", "tension on the tip link", "on the tip link that", "the tip link that increases", "tip link that increases the", "link that increases the open", "that increases the open probability", "increases the open probability of", "the open probability of the", "open probability of the met", "probability of the met channel", "the met channel resulting", "met channel resulting in", "channel resulting in depolarization", "resulting in depolarization of the", "in depolarization of the ohc.", "depolarization of the ohc. deflection", "of the ohc. deflection of", "the ohc. deflection of the", "ohc. deflection of the stereocilia", "of the stereocilia in the", "the stereocilia in the opposite", "stereocilia in the opposite direction", "in the opposite direction produces", "the opposite direction produces compression", "opposite direction produces compression on", "direction produces compression on the", "produces compression on the tip", "compression on the tip link", "the tip link that decreases", "tip link that decreases the", "link that decreases the the", "that decreases the the open", "decreases the the open probability", "the the open probability of", "channel resulting in hyperpolarization", "resulting in hyperpolarization of the", "in hyperpolarization of the ohc.
              sound", "hyperpolarization of the ohc.
              sound causes", "of the ohc.
              sound causes micromechanical", "the ohc.
              sound causes micromechanical motions", "ohc.
              sound causes micromechanical motions of", "causes micromechanical motions of the", "micromechanical motions of the organ", "motions of the organ of", "of the organ of corti", "the organ of corti that", "organ of corti that result", "of corti that result in", "corti that result in alternating", "that result in alternating tension", "result in alternating tension and", "in alternating tension and compression", "alternating tension and compression in", "tension and compression in the", "and compression in the tip", "compression in the tip link", "in the tip link that", "the tip link that produce", "tip link that produce excitatory", "link that produce excitatory inhibitory", "that produce excitatory inhibitory cycles", "produce excitatory inhibitory cycles of", "excitatory inhibitory cycles of met", "inhibitory cycles of met channel", "cycles of met channel openings", "of met channel openings and", "met channel openings and closings", "channel openings and closings relative", "openings and closings relative to", "and closings relative to the", "closings relative to the met", "relative to the met channel's", "to the met channel's resting", "the met channel's resting open", "met channel's resting open probability.", "channel's resting open probability. this", "resting open probability. this causes", "open probability. this causes directionally", "probability. this causes directionally alternating", "this causes directionally alternating fluxes", "causes directionally alternating fluxes of", "directionally alternating fluxes of k+", "alternating fluxes of k+ and", "fluxes of k+ and ca2+", "k+ and ca2+ yielding", "and ca2+ yielding depolarization", "ca2+ yielding depolarization hyperpolarization", "yielding depolarization hyperpolarization cycles that", "depolarization hyperpolarization cycles that cause", "hyperpolarization cycles that cause conformational", "cycles that cause conformational changes", "that cause conformational changes in", "cause conformational changes in prestin", "changes in prestin slc26a5", "in prestin slc26a5 .", "prestin slc26a5 . these", "slc26a5 . these cycles are", ". these cycles are asymmetrical", "cycles are asymmetrical with", "are asymmetrical with contraction", "asymmetrical with contraction caused", "with contraction caused by depolarization", "contraction caused by depolarization dominating", "caused by depolarization dominating elongation", "by depolarization dominating elongation caused", "depolarization dominating elongation caused by", "dominating elongation caused by hyperpolarization", "elongation caused by hyperpolarization due", "caused by hyperpolarization due to", "by hyperpolarization due to the", "hyperpolarization due to the asymmetry", "due to the asymmetry of", "to the asymmetry of the", "the asymmetry of the open", "asymmetry of the open probability", "of the open probability of", "the open probability of met", "open probability of met channels.", "probability of met channels. stereociliary", "of met channels. stereociliary atp2b2", "channels. stereociliary atp2b2 pmca2", "atp2b2 pmca2 extrudes", "pmca2 extrudes calcium ions", "extrudes calcium ions and basally", "calcium ions and basally located", "ions and basally located kcnq4", "and basally located kcnq4 extrudes", "basally located kcnq4 extrudes potassium", "located kcnq4 extrudes potassium ions", "kcnq4 extrudes potassium ions to", "extrudes potassium ions to repolarize", "potassium ions to repolarize the", "ions to repolarize the ohc.", "to repolarize the ohc.
              depolarization", "repolarize the ohc.
              depolarization of", "the ohc.
              depolarization of the", "ohc.
              depolarization of the ohc", "
              depolarization of the ohc causes", "of the ohc causes a", "the ohc causes a decrease", "ohc causes a decrease in", "causes a decrease in length", "a decrease in length of", "decrease in length of the", "in length of the ohc", "length of the ohc due", "of the ohc due to", "the ohc due to a", "ohc due to a very", "due to a very rapid", "a very rapid voltage", "very rapid voltage sensitive", "rapid voltage sensitive change", "voltage sensitive change in conformation", "sensitive change in conformation of", "change in conformation of the", "in conformation of the membrane", "conformation of the membrane protein", "of the membrane protein prestin", "membrane protein prestin slc26a5", "slc26a5 an unusual", "an unusual member of the", "unusual member of the anion", "member of the anion transporter", "of the anion transporter family", "the anion transporter family located", "anion transporter family located in", "transporter family located in the", "family located in the lateral", "located in the lateral membrane", "the lateral membrane mahendrasingam", "lateral membrane mahendrasingam et", "membrane mahendrasingam et al", "mahendrasingam et al 2010", "al 2010 that", "2010 that appears to", "that appears to respond to", "appears to respond to cytosolic", "to respond to cytosolic chloride", "respond to cytosolic chloride by", "to cytosolic chloride by altering", "cytosolic chloride by altering its", "chloride by altering its conformation", "by altering its conformation in", "altering its conformation in the", "its conformation in the plane", "conformation in the plane of", "in the plane of the", "the plane of the plasma", "plane of the plasma membrane", "the plasma membrane reviewed", "plasma membrane reviewed in", "membrane reviewed in dallos", "reviewed in dallos et al.", "in dallos et al. 2006", "et al. 2006 dallos", "al. 2006 dallos 2008", "dallos 2008 hudspeth 2014", "hudspeth 2014 reichenbach and", "2014 reichenbach and hudspeth", "and hudspeth 2014 ashmore", "hudspeth 2014 ashmore 2019", "ashmore 2019 santos sacchi", "2019 santos sacchi 2019", "santos sacchi 2019 . prestin", "sacchi 2019 . prestin also", "2019 . prestin also appears", ". prestin also appears to", "prestin also appears to act", "also appears to act as", "appears to act as a", "to act as a weak", "act as a weak chloride", "as a weak chloride bicarbonate", "a weak chloride bicarbonate antiporter", "chloride bicarbonate antiporter mistrik", "bicarbonate antiporter mistrik et", "antiporter mistrik et al.", "mistrik et al. 2012 .", "et al. 2012 . changes", "al. 2012 . changes in", "2012 . changes in length", ". changes in length of", "changes in length of the", "in length of the ohcs", "length of the ohcs cause", "of the ohcs cause movement", "the ohcs cause movement of", "ohcs cause movement of the", "cause movement of the reticular", "movement of the reticular lamina", "of the reticular lamina toward", "the reticular lamina toward and", "reticular lamina toward and away", "lamina toward and away from", "toward and away from the", "and away from the basilar", "away from the basilar membrane." ] }, { "record_id": "GLY_000594_1_1915", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9674555", "r hsa", "hsa 9674555", "r hsa 9674555" ] }, { "record_id": "GLY_000594_1_1915", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by csf3", "g csf", "signaling by csf3", "csf3 g", "by csf3 g", "csf3 g csf", "signaling by csf3 g", "by csf3 g csf", "is a", "a cytokine", "cytokine that", "that regulates", "regulates production", "production of", "of neutrophils", "neutrophils and", "and granulocytes", "reviewed in", "in panopoulos", "panopoulos and", "and watowich", "watowich 2008", "2008 .", ". csf3", "csf3 circulates", "circulates extracellularly", "extracellularly as", "as a", "a dimer", "dimer and", "and binds", "binds to", "to the", "the monomeric", "monomeric receptor", "receptor csf3r", "on neutrophil", "neutrophil precursors", "precursors and", "and mature", "mature neutrophils", "in futosi", "futosi et", "et al.", "al. 2013", "2013 .", ". csf3r", "csf3r possesses", "possesses no", "no catalytic", "catalytic activity", "activity of", "of its", "its own", "own and", "and is", "is constitutively", "constitutively associated", "associated with", "with the", "the kinases", "kinases lyn", "corey et", "al. 1994", "and jak1", "nicholson et", "1994 .", ". upon", "upon binding", "binding the", "the csf3", "csf3 dimer", "csf3r dimerizes", "is phosphorylated", "and activates", "activates jak", "jak stat", "stat signaling", "ras raf", "raf mek", "mek erk", "erk signaling", "and pi3k", "pi3k signaling", "in basu", "basu et", "al. 2002", "roberts et", "al. 2005", "kendricks and", "and bogoyevitch", "bogoyevitch 2007", "touw and", "and van", "van de", "de geijn", "geijn 2007", "2007 .
              after", ".
              after dimerization", "dimerization of", "of csf3r", "jak1 associated", "with csf3r", "csf3r is", "is required", "required for", "for phosphorylation", "phosphorylation of", "of tyrosine", "tyrosine residues", "residues in", "in the", "the cytosolic", "cytosolic domain", "domain of", "csf3r which", "which recruit", "recruit further", "further kinases", "kinases such", "such as", "as jak2", "and tyk2", "in sampson", "sampson et", "al. 2007", "2007 .", ". phosphorylated", "phosphorylated jak1", "jak1 and", "and jak2", "jak2 then", "then appear", "appear to", "to act", "act redundantly", "redundantly to", "to phosphorylate", "phosphorylate stat", "stat proteins", "which dimerize", "dimerize and", "and transit", "transit to", "the nucleus", "nucleus to", "to activate", "activate gene", "gene expression.
              csf3", "expression.
              csf3 signaling", "signaling also", "also activates", "activates the", "the ras", "ras pathway", "resulting in", "in activation", "activation of", "of erk1", "erk1 and", "and erk2", "erk2 and", "and cellular", "cellular proliferation.", "proliferation. phosphorylated", "phosphorylated csf3r", "csf3r recruits", "recruits both", "both grb2", "which can", "can act", "act as", "a scaffold", "scaffold for", "for ras", "ras guanyl", "guanyl exchange", "exchange factors", "factors sos", "sos and", "and vav", "and ptpn11", "which activates", "activates ras", "ras by", "by dephosphorylating", "dephosphorylating tyrosine", "tyrosine 32", "32 of", "of ras", "bunda et", "al. 2015", "2015 .", ". association", "association of", "of sos", "sos or", "or vav", "vav with", "the phosphorylated", "csf3r has", "has not", "not yet", "yet been", "been shown.", "shown. the", "the pathway", "pathway to", "to activation", "of pi3k", "pi3k is", "is uncertain", "uncertain but", "but appears", "appears to", "to proceed", "proceed via", "via gab2", "gab2 bound", "bound to", "to csf3r.
              mutations", "csf3r.
              mutations in", "in csf3r", "csf3r can", "can occur", "occur during", "during the", "the course", "course of", "of kostmann", "kostmann disease", "a severe", "severe congenital", "congenital neutropenia", "in zeidler", "zeidler and", "and welte", "welte 2002", "zeidler 2005", "ward 2007", "vandenberghe and", "and beel", "beel 2011", "2011 .", ". somatic", "somatic mutations", "mutations in", "principally truncations", "truncations of", "of the", "the c", "c terminal", "terminal region", "are involved", "involved in", "the pathogenesis", "pathogenesis of", "of severe", "neutropenia and", "and are", "are associated", "with progression", "progression to", "to acute", "acute myeloid", "myeloid leukemia", "dong et", "al. 1995", "in ward", "beekman and", "and touw", "touw 2010", "xing and", "and zhao", "zhao 2016", "2016 .", ". loss", "loss or", "or mutation", "mutation of", "region of", "csf3r interferes", "interferes with", "with inhibition", "inhibition and", "and turnover", "turnover of", "the receptor.", "receptor. mutation", "of thr", "thr 618", "618 to", "to ile", "ile 618", "618 in", "csf3r causes", "causes spontaneous", "spontaneous dimerization", "dimerization and", "and consequent", "consequent autoactivation", "autoactivation leading", "leading to", "to csf3", "csf3 independent", "independent signaling", "signaling and", "and chronic", "chronic neutrophilic", "neutrophilic leukemia", "maxson et", "csf3 gcsf", "gcsf is", "is a cytokine", "a cytokine that", "cytokine that regulates", "that regulates production", "regulates production of", "production of neutrophils", "of neutrophils and", "neutrophils and granulocytes", "granulocytes reviewed", "reviewed in panopoulos", "in panopoulos and", "panopoulos and watowich", "and watowich 2008", "watowich 2008 .", "2008 . csf3", ". csf3 circulates", "csf3 circulates extracellularly", "circulates extracellularly as", "extracellularly as a", "as a dimer", "a dimer and", "dimer and binds", "and binds to", "binds to the", "to the monomeric", "the monomeric receptor", "monomeric receptor csf3r", "csf3r gcsfr", "gcsfr on", "on neutrophil precursors", "neutrophil precursors and", "precursors and mature", "and mature neutrophils", "neutrophils reviewed", "reviewed in futosi", "in futosi et", "futosi et al.", "et al. 2013", "al. 2013 .", "2013 . csf3r", ". csf3r possesses", "csf3r possesses no", "possesses no catalytic", "no catalytic activity", "catalytic activity of", "activity of its", "of its own", "its own and", "own and is", "and is constitutively", "is constitutively associated", "constitutively associated with", "associated with the", "with the kinases", "the kinases lyn", "lyn corey", "corey et al.", "et al. 1994", "1994 and", "jak1 nicholson", "nicholson et al.", "al. 1994 .", "1994 . upon", ". upon binding", "upon binding the", "binding the csf3", "the csf3 dimer", "dimer csf3r", "dimerizes is", "phosphorylated and", "and activates jak", "activates jak stat", "jak stat signaling", "signaling ras", "ras raf mek", "raf mek erk", "mek erk signaling", "and pi3k signaling", "signaling reviewed", "reviewed in basu", "in basu et", "basu et al.", "et al. 2002", "2002 roberts", "roberts et al.", "et al. 2005", "2005 kendricks", "kendricks and bogoyevitch", "and bogoyevitch 2007", "2007 touw", "touw and van", "and van de", "van de geijn", "de geijn 2007", "geijn 2007 .
              after", "2007 .
              after dimerization", ".
              after dimerization of", "dimerization of csf3r", "csf3r jak1", "jak1 associated with", "associated with csf3r", "with csf3r is", "csf3r is required", "is required for", "required for phosphorylation", "for phosphorylation of", "phosphorylation of tyrosine", "of tyrosine residues", "tyrosine residues in", "residues in the", "in the cytosolic", "the cytosolic domain", "cytosolic domain of", "domain of csf3r", "of csf3r which", "csf3r which recruit", "which recruit further", "recruit further kinases", "further kinases such", "kinases such as", "such as jak2", "jak2 syk", "syk hck", "hck and", "tyk2 reviewed", "reviewed in sampson", "in sampson et", "sampson et al.", "et al. 2007", "al. 2007 .", "2007 . phosphorylated", ". phosphorylated jak1", "phosphorylated jak1 and", "jak1 and jak2", "and jak2 then", "jak2 then appear", "then appear to", "appear to act", "to act redundantly", "act redundantly to", "redundantly to phosphorylate", "to phosphorylate stat", "phosphorylate stat proteins", "proteins stat1", "stat1 stat3", "stat3 stat5", "stat5 which", "which dimerize and", "dimerize and transit", "and transit to", "transit to the", "to the nucleus", "the nucleus to", "nucleus to activate", "to activate gene", "activate gene expression.
              csf3", "gene expression.
              csf3 signaling", "expression.
              csf3 signaling also", "signaling also activates", "also activates the", "activates the ras", "the ras pathway", "pathway resulting", "resulting in activation", "in activation of", "activation of erk1", "of erk1 and", "erk1 and erk2", "and erk2 and", "erk2 and cellular", "and cellular proliferation.", "cellular proliferation. phosphorylated", "proliferation. phosphorylated csf3r", "phosphorylated csf3r recruits", "csf3r recruits both", "recruits both grb2", "grb2 which", "which can act", "can act as", "act as a", "as a scaffold", "a scaffold for", "scaffold for ras", "for ras guanyl", "ras guanyl exchange", "guanyl exchange factors", "exchange factors sos", "factors sos and", "sos and vav", "vav and", "ptpn11 shp2", "which activates ras", "activates ras by", "ras by dephosphorylating", "by dephosphorylating tyrosine", "dephosphorylating tyrosine 32", "tyrosine 32 of", "32 of ras", "ras bunda", "bunda et al.", "et al. 2015", "al. 2015 .", "2015 . association", ". association of", "association of sos", "of sos or", "sos or vav", "or vav with", "vav with the", "with the phosphorylated", "the phosphorylated csf3r", "phosphorylated csf3r has", "csf3r has not", "has not yet", "not yet been", "yet been shown.", "been shown. the", "shown. the pathway", "the pathway to", "pathway to activation", "to activation of", "activation of pi3k", "of pi3k is", "pi3k is uncertain", "is uncertain but", "uncertain but appears", "but appears to", "appears to proceed", "to proceed via", "proceed via gab2", "via gab2 bound", "gab2 bound to", "bound to csf3r.
              mutations", "to csf3r.
              mutations in", "csf3r.
              mutations in csf3r", "in csf3r can", "csf3r can occur", "can occur during", "occur during the", "during the course", "the course of", "course of kostmann", "of kostmann disease", "disease a", "a severe congenital", "severe congenital neutropenia", "neutropenia reviewed", "reviewed in zeidler", "in zeidler and", "zeidler and welte", "and welte 2002", "2002 zeidler", "2005 ward", "2007 vandenberghe", "vandenberghe and beel", "and beel 2011", "beel 2011 .", "2011 . somatic", ". somatic mutations", "somatic mutations in", "mutations in csf3r", "csf3r principally", "principally truncations of", "truncations of the", "of the c", "the c terminal", "c terminal region", "region are", "are involved in", "involved in the", "in the pathogenesis", "the pathogenesis of", "pathogenesis of severe", "of severe congenital", "congenital neutropenia and", "neutropenia and are", "and are associated", "are associated with", "associated with progression", "with progression to", "progression to acute", "to acute myeloid", "acute myeloid leukemia", "leukemia dong", "dong et al.", "et al. 1995", "1995 reviewed", "reviewed in ward", "in ward 2007", "2007 beekman", "beekman and touw", "and touw 2010", "2010 xing", "xing and zhao", "and zhao 2016", "zhao 2016 .", "2016 . loss", ". loss or", "loss or mutation", "or mutation of", "mutation of the", "terminal region of", "region of csf3r", "of csf3r interferes", "csf3r interferes with", "interferes with inhibition", "with inhibition and", "inhibition and turnover", "and turnover of", "turnover of the", "of the receptor.", "the receptor. mutation", "receptor. mutation of", "mutation of thr", "of thr 618", "thr 618 to", "618 to ile", "to ile 618", "ile 618 in", "618 in csf3r", "in csf3r causes", "csf3r causes spontaneous", "causes spontaneous dimerization", "spontaneous dimerization and", "dimerization and consequent", "and consequent autoactivation", "consequent autoactivation leading", "autoactivation leading to", "leading to csf3", "to csf3 independent", "csf3 independent signaling", "independent signaling and", "signaling and chronic", "and chronic neutrophilic", "chronic neutrophilic leukemia", "leukemia maxson", "maxson et al.", "gcsf is a", "is a cytokine that", "a cytokine that regulates", "cytokine that regulates production", "that regulates production of", "regulates production of neutrophils", "production of neutrophils and", "of neutrophils and granulocytes", "and granulocytes reviewed", "granulocytes reviewed in", "reviewed in panopoulos and", "in panopoulos and watowich", "panopoulos and watowich 2008", "and watowich 2008 .", "watowich 2008 . csf3", "2008 . csf3 circulates", ". csf3 circulates extracellularly", "csf3 circulates extracellularly as", "circulates extracellularly as a", "extracellularly as a dimer", "as a dimer and", "a dimer and binds", "dimer and binds to", "and binds to the", "binds to the monomeric", "to the monomeric receptor", "the monomeric receptor csf3r", "receptor csf3r gcsfr", "gcsfr on neutrophil", "on neutrophil precursors and", "neutrophil precursors and mature", "precursors and mature neutrophils", "mature neutrophils reviewed", "neutrophils reviewed in", "reviewed in futosi et", "in futosi et al.", "futosi et al. 2013", "et al. 2013 .", "al. 2013 . csf3r", "2013 . csf3r possesses", ". csf3r possesses no", "csf3r possesses no catalytic", "possesses no catalytic activity", "no catalytic activity of", "catalytic activity of its", "activity of its own", "of its own and", "its own and is", "own and is constitutively", "and is constitutively associated", "is constitutively associated with", "constitutively associated with the", "associated with the kinases", "with the kinases lyn", "kinases lyn corey", "lyn corey et", "corey et al. 1994", "al. 1994 and", "1994 and jak1", "and jak1 nicholson", "jak1 nicholson et", "nicholson et al. 1994", "et al. 1994 .", "al. 1994 . upon", "1994 . upon binding", ". upon binding the", "upon binding the csf3", "binding the csf3 dimer", "csf3 dimer csf3r", "dimer csf3r dimerizes", "csf3r dimerizes is", "dimerizes is phosphorylated", "is phosphorylated and", "phosphorylated and activates", "and activates jak stat", "activates jak stat signaling", "stat signaling ras", "signaling ras raf", "ras raf mek erk", "raf mek erk signaling", "erk signaling and", "signaling and pi3k", "pi3k signaling reviewed", "signaling reviewed in", "reviewed in basu et", "in basu et al.", "basu et al. 2002", "al. 2002 roberts", "2002 roberts et", "roberts et al. 2005", "al. 2005 kendricks", "2005 kendricks and", "kendricks and bogoyevitch 2007", "bogoyevitch 2007 touw", "2007 touw and", "touw and van de", "and van de geijn", "van de geijn 2007", "de geijn 2007 .
              after", "geijn 2007 .
              after dimerization", "2007 .
              after dimerization of", ".
              after dimerization of csf3r", "of csf3r jak1", "csf3r jak1 associated", "jak1 associated with csf3r", "associated with csf3r is", "with csf3r is required", "csf3r is required for", "is required for phosphorylation", "required for phosphorylation of", "for phosphorylation of tyrosine", "phosphorylation of tyrosine residues", "of tyrosine residues in", "tyrosine residues in the", "residues in the cytosolic", "in the cytosolic domain", "the cytosolic domain of", "cytosolic domain of csf3r", "domain of csf3r which", "of csf3r which recruit", "csf3r which recruit further", "which recruit further kinases", "recruit further kinases such", "further kinases such as", "kinases such as jak2", "as jak2 syk", "hck and tyk2", "and tyk2 reviewed", "tyk2 reviewed in", "reviewed in sampson et", "in sampson et al.", "sampson et al. 2007", "et al. 2007 .", "al. 2007 . phosphorylated", "2007 . phosphorylated jak1", ". phosphorylated jak1 and", "phosphorylated jak1 and jak2", "jak1 and jak2 then", "and jak2 then appear", "jak2 then appear to", "then appear to act", "appear to act redundantly", "to act redundantly to", "act redundantly to phosphorylate", "redundantly to phosphorylate stat", "to phosphorylate stat proteins", "stat proteins stat1", "stat5 which dimerize", "which dimerize and transit", "dimerize and transit to", "and transit to the", "transit to the nucleus", "to the nucleus to", "the nucleus to activate", "nucleus to activate gene", "to activate gene expression.
              csf3", "activate gene expression.
              csf3 signaling", "gene expression.
              csf3 signaling also", "expression.
              csf3 signaling also activates", "signaling also activates the", "also activates the ras", "activates the ras pathway", "ras pathway resulting", "pathway resulting in", "resulting in activation of", "in activation of erk1", "activation of erk1 and", "of erk1 and erk2", "erk1 and erk2 and", "and erk2 and cellular", "erk2 and cellular proliferation.", "and cellular proliferation. phosphorylated", "cellular proliferation. phosphorylated csf3r", "proliferation. phosphorylated csf3r recruits", "phosphorylated csf3r recruits both", "csf3r recruits both grb2", "both grb2 which", "grb2 which can", "which can act as", "can act as a", "act as a scaffold", "as a scaffold for", "a scaffold for ras", "scaffold for ras guanyl", "for ras guanyl exchange", "ras guanyl exchange factors", "guanyl exchange factors sos", "exchange factors sos and", "factors sos and vav", "and vav and", "vav and ptpn11", "and ptpn11 shp2", "shp2 which", "which activates ras by", "activates ras by dephosphorylating", "ras by dephosphorylating tyrosine", "by dephosphorylating tyrosine 32", "dephosphorylating tyrosine 32 of", "tyrosine 32 of ras", "of ras bunda", "ras bunda et", "bunda et al. 2015", "et al. 2015 .", "al. 2015 . association", "2015 . association of", ". association of sos", "association of sos or", "of sos or vav", "sos or vav with", "or vav with the", "vav with the phosphorylated", "with the phosphorylated csf3r", "the phosphorylated csf3r has", "phosphorylated csf3r has not", "csf3r has not yet", "has not yet been", "not yet been shown.", "yet been shown. the", "been shown. the pathway", "shown. the pathway to", "the pathway to activation", "pathway to activation of", "to activation of pi3k", "activation of pi3k is", "of pi3k is uncertain", "pi3k is uncertain but", "is uncertain but appears", "uncertain but appears to", "but appears to proceed", "appears to proceed via", "to proceed via gab2", "proceed via gab2 bound", "via gab2 bound to", "gab2 bound to csf3r.
              mutations", "bound to csf3r.
              mutations in", "to csf3r.
              mutations in csf3r", "csf3r.
              mutations in csf3r can", "in csf3r can occur", "csf3r can occur during", "can occur during the", "occur during the course", "during the course of", "the course of kostmann", "course of kostmann disease", "kostmann disease a", "disease a severe", "a severe congenital neutropenia", "congenital neutropenia reviewed", "neutropenia reviewed in", "reviewed in zeidler and", "in zeidler and welte", "zeidler and welte 2002", "welte 2002 zeidler", "2002 zeidler 2005", "zeidler 2005 ward", "2005 ward 2007", "ward 2007 vandenberghe", "2007 vandenberghe and", "vandenberghe and beel 2011", "and beel 2011 .", "beel 2011 . somatic", "2011 . somatic mutations", ". somatic mutations in", "somatic mutations in csf3r", "in csf3r principally", "csf3r principally truncations", "principally truncations of the", "truncations of the c", "of the c terminal", "the c terminal region", "terminal region are", "region are involved", "are involved in the", "involved in the pathogenesis", "in the pathogenesis of", "the pathogenesis of severe", "pathogenesis of severe congenital", "of severe congenital neutropenia", "severe congenital neutropenia and", "congenital neutropenia and are", "neutropenia and are associated", "and are associated with", "are associated with progression", "associated with progression to", "with progression to acute", "progression to acute myeloid", "to acute myeloid leukemia", "myeloid leukemia dong", "leukemia dong et", "dong et al. 1995", "al. 1995 reviewed", "1995 reviewed in", "reviewed in ward 2007", "ward 2007 beekman", "2007 beekman and", "beekman and touw 2010", "touw 2010 xing", "2010 xing and", "xing and zhao 2016", "and zhao 2016 .", "zhao 2016 . loss", "2016 . loss or", ". loss or mutation", "loss or mutation of", "or mutation of the", "mutation of the c", "c terminal region of", "terminal region of csf3r", "region of csf3r interferes", "of csf3r interferes with", "csf3r interferes with inhibition", "interferes with inhibition and", "with inhibition and turnover", "inhibition and turnover of", "and turnover of the", "turnover of the receptor.", "of the receptor. mutation", "the receptor. mutation of", "receptor. mutation of thr", "mutation of thr 618", "of thr 618 to", "thr 618 to ile", "618 to ile 618", "to ile 618 in", "ile 618 in csf3r", "618 in csf3r causes", "in csf3r causes spontaneous", "csf3r causes spontaneous dimerization", "causes spontaneous dimerization and", "spontaneous dimerization and consequent", "dimerization and consequent autoactivation", "and consequent autoactivation leading", "consequent autoactivation leading to", "autoactivation leading to csf3", "leading to csf3 independent", "to csf3 independent signaling", "csf3 independent signaling and", "independent signaling and chronic", "signaling and chronic neutrophilic", "and chronic neutrophilic leukemia", "neutrophilic leukemia maxson", "leukemia maxson et", "maxson et al. 2013", "csf3 gcsf is", "gcsf is a cytokine", "is a cytokine that regulates", "a cytokine that regulates production", "cytokine that regulates production of", "that regulates production of neutrophils", "regulates production of neutrophils and", "production of neutrophils and granulocytes", "neutrophils and granulocytes reviewed", "and granulocytes reviewed in", "granulocytes reviewed in panopoulos", "reviewed in panopoulos and watowich", "in panopoulos and watowich 2008", "panopoulos and watowich 2008 .", "and watowich 2008 . csf3", "watowich 2008 . csf3 circulates", "2008 . csf3 circulates extracellularly", ". csf3 circulates extracellularly as", "csf3 circulates extracellularly as a", "circulates extracellularly as a dimer", "extracellularly as a dimer and", "as a dimer and binds", "a dimer and binds to", "dimer and binds to the", "and binds to the monomeric", "binds to the monomeric receptor", "to the monomeric receptor csf3r", "monomeric receptor csf3r gcsfr", "csf3r gcsfr on", "gcsfr on neutrophil precursors", "on neutrophil precursors and mature", "neutrophil precursors and mature neutrophils", "and mature neutrophils reviewed", "mature neutrophils reviewed in", "neutrophils reviewed in futosi", "reviewed in futosi et al.", "in futosi et al. 2013", "futosi et al. 2013 .", "et al. 2013 . csf3r", "al. 2013 . csf3r possesses", "2013 . csf3r possesses no", ". csf3r possesses no catalytic", "csf3r possesses no catalytic activity", "possesses no catalytic activity of", "no catalytic activity of its", "catalytic activity of its own", "activity of its own and", "of its own and is", "its own and is constitutively", "own and is constitutively associated", "and is constitutively associated with", "is constitutively associated with the", "constitutively associated with the kinases", "associated with the kinases lyn", "the kinases lyn corey", "kinases lyn corey et", "lyn corey et al.", "et al. 1994 and", "al. 1994 and jak1", "and jak1 nicholson et", "jak1 nicholson et al.", "nicholson et al. 1994 .", "et al. 1994 . upon", "al. 1994 . upon binding", "1994 . upon binding the", ". upon binding the csf3", "upon binding the csf3 dimer", "the csf3 dimer csf3r", "csf3 dimer csf3r dimerizes", "csf3r dimerizes is phosphorylated", "is phosphorylated and activates", "phosphorylated and activates jak", "and activates jak stat signaling", "jak stat signaling ras", "stat signaling ras raf", "signaling ras raf mek", "ras raf mek erk signaling", "mek erk signaling and", "erk signaling and pi3k", "signaling and pi3k signaling", "and pi3k signaling reviewed", "pi3k signaling reviewed in", "signaling reviewed in basu", "reviewed in basu et al.", "in basu et al. 2002", "et al. 2002 roberts", "al. 2002 roberts et", "2002 roberts et al.", "et al. 2005 kendricks", "al. 2005 kendricks and", "2005 kendricks and bogoyevitch", "and bogoyevitch 2007 touw", "bogoyevitch 2007 touw and", "2007 touw and van", "touw and van de geijn", "and van de geijn 2007", "van de geijn 2007 .
              after", "de geijn 2007 .
              after dimerization", "geijn 2007 .
              after dimerization of", "2007 .
              after dimerization of csf3r", "dimerization of csf3r jak1", "of csf3r jak1 associated", "csf3r jak1 associated with", "jak1 associated with csf3r is", "associated with csf3r is required", "with csf3r is required for", "csf3r is required for phosphorylation", "is required for phosphorylation of", "required for phosphorylation of tyrosine", "for phosphorylation of tyrosine residues", "phosphorylation of tyrosine residues in", "of tyrosine residues in the", "tyrosine residues in the cytosolic", "residues in the cytosolic domain", "in the cytosolic domain of", "the cytosolic domain of csf3r", "cytosolic domain of csf3r which", "domain of csf3r which recruit", "of csf3r which recruit further", "csf3r which recruit further kinases", "which recruit further kinases such", "recruit further kinases such as", "further kinases such as jak2", "such as jak2 syk", "jak2 syk hck", "syk hck and", "and tyk2 reviewed in", "tyk2 reviewed in sampson", "reviewed in sampson et al.", "in sampson et al. 2007", "sampson et al. 2007 .", "et al. 2007 . phosphorylated", "al. 2007 . phosphorylated jak1", "2007 . phosphorylated jak1 and", ". phosphorylated jak1 and jak2", "phosphorylated jak1 and jak2 then", "jak1 and jak2 then appear", "and jak2 then appear to", "jak2 then appear to act", "then appear to act redundantly", "appear to act redundantly to", "to act redundantly to phosphorylate", "act redundantly to phosphorylate stat", "redundantly to phosphorylate stat proteins", "phosphorylate stat proteins stat1", "proteins stat1 stat3", "stat1 stat3 stat5", "stat3 stat5 which", "stat5 which dimerize and", "which dimerize and transit to", "dimerize and transit to the", "and transit to the nucleus", "transit to the nucleus to", "to the nucleus to activate", "the nucleus to activate gene", "nucleus to activate gene expression.
              csf3", "to activate gene expression.
              csf3 signaling", "activate gene expression.
              csf3 signaling also", "gene expression.
              csf3 signaling also activates", "expression.
              csf3 signaling also activates the", "signaling also activates the ras", "also activates the ras pathway", "the ras pathway resulting", "ras pathway resulting in", "pathway resulting in activation", "resulting in activation of erk1", "in activation of erk1 and", "activation of erk1 and erk2", "of erk1 and erk2 and", "erk1 and erk2 and cellular", "and erk2 and cellular proliferation.", "erk2 and cellular proliferation. phosphorylated", "and cellular proliferation. phosphorylated csf3r", "cellular proliferation. phosphorylated csf3r recruits", "proliferation. phosphorylated csf3r recruits both", "phosphorylated csf3r recruits both grb2", "recruits both grb2 which", "both grb2 which can", "grb2 which can act", "which can act as a", "can act as a scaffold", "act as a scaffold for", "as a scaffold for ras", "a scaffold for ras guanyl", "scaffold for ras guanyl exchange", "for ras guanyl exchange factors", "ras guanyl exchange factors sos", "guanyl exchange factors sos and", "exchange factors sos and vav", "sos and vav and", "and vav and ptpn11", "shp2 which activates", "which activates ras by dephosphorylating", "activates ras by dephosphorylating tyrosine", "ras by dephosphorylating tyrosine 32", "by dephosphorylating tyrosine 32 of", "dephosphorylating tyrosine 32 of ras", "32 of ras bunda", "of ras bunda et", "ras bunda et al.", "bunda et al. 2015 .", "et al. 2015 . association", "al. 2015 . association of", "2015 . association of sos", ". association of sos or", "association of sos or vav", "of sos or vav with", "sos or vav with the", "or vav with the phosphorylated", "vav with the phosphorylated csf3r", "with the phosphorylated csf3r has", "the phosphorylated csf3r has not", "phosphorylated csf3r has not yet", "csf3r has not yet been", "has not yet been shown.", "not yet been shown. the", "yet been shown. the pathway", "been shown. the pathway to", "shown. the pathway to activation", "the pathway to activation of", "pathway to activation of pi3k", "to activation of pi3k is", "activation of pi3k is uncertain", "of pi3k is uncertain but", "pi3k is uncertain but appears", "is uncertain but appears to", "uncertain but appears to proceed", "but appears to proceed via", "appears to proceed via gab2", "to proceed via gab2 bound", "proceed via gab2 bound to", "via gab2 bound to csf3r.
              mutations", "gab2 bound to csf3r.
              mutations in", "bound to csf3r.
              mutations in csf3r", "to csf3r.
              mutations in csf3r can", "csf3r.
              mutations in csf3r can occur", "in csf3r can occur during", "csf3r can occur during the", "can occur during the course", "occur during the course of", "during the course of kostmann", "the course of kostmann disease", "of kostmann disease a", "kostmann disease a severe", "disease a severe congenital", "severe congenital neutropenia reviewed", "congenital neutropenia reviewed in", "neutropenia reviewed in zeidler", "reviewed in zeidler and welte", "in zeidler and welte 2002", "and welte 2002 zeidler", "welte 2002 zeidler 2005", "zeidler 2005 ward 2007", "ward 2007 vandenberghe and", "2007 vandenberghe and beel", "vandenberghe and beel 2011 .", "and beel 2011 . somatic", "beel 2011 . somatic mutations", "2011 . somatic mutations in", ". somatic mutations in csf3r", "mutations in csf3r principally", "in csf3r principally truncations", "csf3r principally truncations of", "principally truncations of the c", "truncations of the c terminal", "of the c terminal region", "c terminal region are", "terminal region are involved", "region are involved in", "are involved in the pathogenesis", "involved in the pathogenesis of", "in the pathogenesis of severe", "the pathogenesis of severe congenital", "pathogenesis of severe congenital neutropenia", "of severe congenital neutropenia and", "severe congenital neutropenia and are", "congenital neutropenia and are associated", "neutropenia and are associated with", "and are associated with progression", "are associated with progression to", "associated with progression to acute", "with progression to acute myeloid", "progression to acute myeloid leukemia", "acute myeloid leukemia dong", "myeloid leukemia dong et", "leukemia dong et al.", "et al. 1995 reviewed", "al. 1995 reviewed in", "1995 reviewed in ward", "in ward 2007 beekman", "ward 2007 beekman and", "2007 beekman and touw", "and touw 2010 xing", "touw 2010 xing and", "2010 xing and zhao", "xing and zhao 2016 .", "and zhao 2016 . loss", "zhao 2016 . loss or", "2016 . loss or mutation", ". loss or mutation of", "loss or mutation of the", "or mutation of the c", "mutation of the c terminal", "the c terminal region of", "c terminal region of csf3r", "terminal region of csf3r interferes", "region of csf3r interferes with", "of csf3r interferes with inhibition", "csf3r interferes with inhibition and", "interferes with inhibition and turnover", "with inhibition and turnover of", "inhibition and turnover of the", "and turnover of the receptor.", "turnover of the receptor. mutation", "of the receptor. mutation of", "the receptor. mutation of thr", "receptor. mutation of thr 618", "mutation of thr 618 to", "of thr 618 to ile", "thr 618 to ile 618", "618 to ile 618 in", "to ile 618 in csf3r", "ile 618 in csf3r causes", "618 in csf3r causes spontaneous", "in csf3r causes spontaneous dimerization", "csf3r causes spontaneous dimerization and", "causes spontaneous dimerization and consequent", "spontaneous dimerization and consequent autoactivation", "dimerization and consequent autoactivation leading", "and consequent autoactivation leading to", "consequent autoactivation leading to csf3", "autoactivation leading to csf3 independent", "leading to csf3 independent signaling", "to csf3 independent signaling and", "csf3 independent signaling and chronic", "independent signaling and chronic neutrophilic", "signaling and chronic neutrophilic leukemia", "chronic neutrophilic leukemia maxson", "neutrophilic leukemia maxson et", "leukemia maxson et al.", "maxson et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1916", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9696264", "r hsa", "hsa 9696264", "r hsa 9696264" ] }, { "record_id": "GLY_000594_1_1916", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rnd3 gtpase", "gtpase cycle", "rnd3 gtpase cycle", "is an", "an atypical", "atypical rho", "rho gtpase", "gtpase from", "from the", "the rnd", "rnd subfamily.", "subfamily. rnd3", "rnd3 is", "is constitutively", "constitutively bound", "bound to", "to gtp", "gtp and", "and lacks", "lacks gtpase", "gtpase activity.", "activity. no", "no guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "gtpase activator", "activator proteins", "or guanine", "nucleotide dissociation", "dissociation inhibitors", "act on", "on rnd3.", "rnd3. rnd3", "is a", "a direct", "direct antagonist", "antagonist of", "of rock1", "rock1 kinase", "kinase activity.", "activity. rnd3", "rnd3 prevents", "prevents phosphorylation", "phosphorylation of", "rock1 targets", "targets and", "similar to", "to rnd1", "induces stress", "stress fiber", "fiber disassembly.", "disassembly. rnd3", "rnd3 regulates", "regulates cell", "cell migration", "establishment of", "of neuronal", "neuronal polarity", "heart development", "and myometrium", "myometrium changes", "changes during", "during pregnancy.", "pregnancy. defective", "defective rnd3", "rnd3 function", "function is", "is related", "related to", "to cardiomyopathy", "hydrocephalus and", "and cancer.", "cancer. like", "like rnd1", "is implicated", "implicated both", "both as", "as a", "a tumor", "tumor suppressor", "suppressor and", "and an", "an oncogene", "oncogene in", "in cancer", "and can", "can both", "both increase", "increase and", "and decrease", "decrease sensitivity", "sensitivity to", "to chemotherapeutic", "chemotherapeutic agents", "which depends", "depends on", "on cancer", "cancer type", "type and", "and stage.", "stage. for", "for review", "please refer", "refer to", "to jie", "jie et", "et al.", "al. 2015", "2015 and", "and paysan", "paysan et", "al. 2016.", "rnd3 rhoe", "rhoe is", "is an atypical", "an atypical rho", "atypical rho gtpase", "rho gtpase from", "gtpase from the", "from the rnd", "the rnd subfamily.", "rnd subfamily. rnd3", "subfamily. rnd3 is", "rnd3 is constitutively", "is constitutively bound", "constitutively bound to", "bound to gtp", "to gtp and", "gtp and lacks", "and lacks gtpase", "lacks gtpase activity.", "gtpase activity. no", "activity. no guanine", "no guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factors", "factors gefs", "gtpase activator proteins", "proteins gaps", "gaps or", "or guanine nucleotide", "guanine nucleotide dissociation", "nucleotide dissociation inhibitors", "inhibitors gdis", "gdis act", "act on rnd3.", "on rnd3. rnd3", "rnd3. rnd3 is", "rnd3 is a", "is a direct", "a direct antagonist", "direct antagonist of", "antagonist of rock1", "of rock1 kinase", "rock1 kinase activity.", "kinase activity. rnd3", "activity. rnd3 prevents", "rnd3 prevents phosphorylation", "prevents phosphorylation of", "phosphorylation of rock1", "of rock1 targets", "rock1 targets and", "and similar", "similar to rnd1", "rnd1 induces", "induces stress fiber", "stress fiber disassembly.", "fiber disassembly. rnd3", "disassembly. rnd3 regulates", "rnd3 regulates cell", "regulates cell migration", "migration establishment", "establishment of neuronal", "of neuronal polarity", "polarity heart", "development and", "and myometrium changes", "myometrium changes during", "changes during pregnancy.", "during pregnancy. defective", "pregnancy. defective rnd3", "defective rnd3 function", "rnd3 function is", "function is related", "is related to", "related to cardiomyopathy", "cardiomyopathy hydrocephalus", "hydrocephalus and cancer.", "and cancer. like", "cancer. like rnd1", "rnd1 rnd3", "rnd3 is implicated", "is implicated both", "implicated both as", "both as a", "as a tumor", "a tumor suppressor", "tumor suppressor and", "suppressor and an", "and an oncogene", "an oncogene in", "oncogene in cancer", "cancer and", "and can both", "can both increase", "both increase and", "increase and decrease", "and decrease sensitivity", "decrease sensitivity to", "sensitivity to chemotherapeutic", "to chemotherapeutic agents", "agents which", "which depends on", "depends on cancer", "on cancer type", "cancer type and", "type and stage.", "and stage. for", "stage. for review", "review please", "please refer to", "refer to jie", "to jie et", "jie et al.", "et al. 2015", "al. 2015 and", "2015 and paysan", "and paysan et", "paysan et al.", "et al. 2016.", "rhoe is an", "is an atypical rho", "an atypical rho gtpase", "atypical rho gtpase from", "rho gtpase from the", "gtpase from the rnd", "from the rnd subfamily.", "the rnd subfamily. rnd3", "rnd subfamily. rnd3 is", "subfamily. rnd3 is constitutively", "rnd3 is constitutively bound", "is constitutively bound to", "constitutively bound to gtp", "bound to gtp and", "to gtp and lacks", "gtp and lacks gtpase", "and lacks gtpase activity.", "lacks gtpase activity. no", "gtpase activity. no guanine", "activity. no guanine nucleotide", "no guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs gtpase", "activator proteins gaps", "gaps or guanine", "or guanine nucleotide dissociation", "guanine nucleotide dissociation inhibitors", "dissociation inhibitors gdis", "gdis act on", "act on rnd3. rnd3", "on rnd3. rnd3 is", "rnd3. rnd3 is a", "rnd3 is a direct", "is a direct antagonist", "a direct antagonist of", "direct antagonist of rock1", "antagonist of rock1 kinase", "of rock1 kinase activity.", "rock1 kinase activity. rnd3", "kinase activity. rnd3 prevents", "activity. rnd3 prevents phosphorylation", "rnd3 prevents phosphorylation of", "prevents phosphorylation of rock1", "phosphorylation of rock1 targets", "of rock1 targets and", "targets and similar", "and similar to", "to rnd1 induces", "rnd1 induces stress", "induces stress fiber disassembly.", "stress fiber disassembly. rnd3", "fiber disassembly. rnd3 regulates", "disassembly. rnd3 regulates cell", "rnd3 regulates cell migration", "cell migration establishment", "migration establishment of", "establishment of neuronal polarity", "neuronal polarity heart", "polarity heart development", "heart development and", "development and myometrium", "and myometrium changes during", "myometrium changes during pregnancy.", "changes during pregnancy. defective", "during pregnancy. defective rnd3", "pregnancy. defective rnd3 function", "defective rnd3 function is", "rnd3 function is related", "function is related to", "is related to cardiomyopathy", "to cardiomyopathy hydrocephalus", "cardiomyopathy hydrocephalus and", "hydrocephalus and cancer. like", "and cancer. like rnd1", "like rnd1 rnd3", "rnd1 rnd3 is", "rnd3 is implicated both", "is implicated both as", "implicated both as a", "both as a tumor", "as a tumor suppressor", "a tumor suppressor and", "tumor suppressor and an", "suppressor and an oncogene", "and an oncogene in", "an oncogene in cancer", "in cancer and", "cancer and can", "and can both increase", "can both increase and", "both increase and decrease", "increase and decrease sensitivity", "and decrease sensitivity to", "decrease sensitivity to chemotherapeutic", "sensitivity to chemotherapeutic agents", "chemotherapeutic agents which", "agents which depends", "which depends on cancer", "depends on cancer type", "on cancer type and", "cancer type and stage.", "type and stage. for", "and stage. for review", "for review please", "review please refer", "please refer to jie", "refer to jie et", "to jie et al.", "jie et al. 2015", "et al. 2015 and", "al. 2015 and paysan", "2015 and paysan et", "and paysan et al.", "paysan et al. 2016.", "rnd3 rhoe is", "rhoe is an atypical", "is an atypical rho gtpase", "an atypical rho gtpase from", "atypical rho gtpase from the", "rho gtpase from the rnd", "gtpase from the rnd subfamily.", "from the rnd subfamily. rnd3", "the rnd subfamily. rnd3 is", "rnd subfamily. rnd3 is constitutively", "subfamily. rnd3 is constitutively bound", "rnd3 is constitutively bound to", "is constitutively bound to gtp", "constitutively bound to gtp and", "bound to gtp and lacks", "to gtp and lacks gtpase", "gtp and lacks gtpase activity.", "and 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cardiomyopathy hydrocephalus and", "cardiomyopathy hydrocephalus and cancer.", "hydrocephalus and cancer. like rnd1", "cancer. like rnd1 rnd3", "like rnd1 rnd3 is", "rnd1 rnd3 is implicated", "rnd3 is implicated both as", "is implicated both as a", "implicated both as a tumor", "both as a tumor suppressor", "as a tumor suppressor and", "a tumor suppressor and an", "tumor suppressor and an oncogene", "suppressor and an oncogene in", "and an oncogene in cancer", "oncogene in cancer and", "in cancer and can", "cancer and can both", "and can both increase and", "can both increase and decrease", "both increase and decrease sensitivity", "increase and decrease sensitivity to", "and decrease sensitivity to chemotherapeutic", "decrease sensitivity to chemotherapeutic agents", "to chemotherapeutic agents which", "chemotherapeutic agents which depends", "agents which depends on", "which depends on cancer type", "depends on cancer type and", "on cancer type and stage.", "cancer type and stage. for", "type and stage. for review", "stage. for review please", "for review please refer", "review please refer to", "please refer to jie et", "refer to jie et al.", "to jie et al. 2015", "jie et al. 2015 and", "et al. 2015 and paysan", "al. 2015 and paysan et", "2015 and paysan et al.", "and paysan et al. 2016." ] }, { "record_id": "GLY_000594_1_1917", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9696270", "r hsa", "hsa 9696270", "r hsa 9696270" ] }, { "record_id": "GLY_000594_1_1917", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rnd2 gtpase", "gtpase cycle", "rnd2 gtpase cycle", "is an", "an atypical", "atypical rho", "rho gtpase", "gtpase and", "and the", "the least", "least studied", "studied member", "member of", "of the", "the rnd", "rnd subfamily.", "subfamily. rnd2", "rnd2 is", "is constitutively", "constitutively bound", "bound to", "to gtp", "gtp and", "and lacks", "lacks 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1999", "al. 1999 .", "1999 . rnd2", ". rnd2 regulates", "rnd2 regulates neurite", "regulates neurite outgrowth", "neurite outgrowth and", "outgrowth and branching", "branching fujita", "fujita et al.", "et al. 2002", "2002 kakimoto", "kakimoto et al.", "et al. 2004", "2004 tanaka", "tanaka et al.", "et al. 2006", "2006 wakita", "wakita et al.", "et al. 2011", "2011 and", "and migration of", "migration of newborn", "of newborn neurons", "newborn neurons within", "neurons within the", "within the embryonic", "the embryonic cerebral", "embryonic cerebral cortex", "cortex nakamura", "nakamura et al.", "2006 heng", "heng et al.", "et al. 2008", "2008 alfano", "alfano et al.", "2011 pacary", "pacary et al.", "2011 gladwyn", "gladwyn ng et", "ng et al.", "et al. 2015", "2015 heng", "al. 2015 .", "rhon is an", "is an atypical rho", "an atypical rho gtpase", "atypical rho gtpase and", "rho gtpase and the", "gtpase and the least", "and the least studied", "the least studied member", "least 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et", "nobes et al. 1998", "al. 1998 nishi", "1998 nishi et", "nishi et al. 1999", "et al. 1999 .", "al. 1999 . rnd2", "1999 . rnd2 regulates", ". rnd2 regulates neurite", "rnd2 regulates neurite outgrowth", "regulates neurite outgrowth and", "neurite outgrowth and branching", "and branching fujita", "branching fujita et", "fujita et al. 2002", "al. 2002 kakimoto", "2002 kakimoto et", "kakimoto et al. 2004", "al. 2004 tanaka", "2004 tanaka et", "tanaka et al. 2006", "al. 2006 wakita", "2006 wakita et", "wakita et al. 2011", "al. 2011 and", "2011 and migration", "and migration of newborn", "migration of newborn neurons", "of newborn neurons within", "newborn neurons within the", "neurons within the embryonic", "within the embryonic cerebral", "the embryonic cerebral cortex", "cerebral cortex nakamura", "cortex nakamura et", "nakamura et al. 2006", "al. 2006 heng", "2006 heng et", "heng et al. 2008", "al. 2008 alfano", "2008 alfano et", "alfano et al. 2011", "al. 2011 pacary", "2011 pacary et", "pacary et al. 2011", "al. 2011 gladwyn", "2011 gladwyn ng", "gladwyn ng et al.", "ng et al. 2015", "al. 2015 heng", "2015 heng et", "heng et al. 2015", "et al. 2015 .", "rnd2 rhon is", "rhon is an atypical", "is an atypical rho gtpase", "an atypical rho gtpase and", "atypical rho gtpase and the", "rho gtpase and the least", "gtpase and the least studied", "and the least studied member", "the least studied member of", "least studied member of the", "studied member of the rnd", "member of the rnd subfamily.", "of the rnd subfamily. rnd2", "the rnd subfamily. rnd2 is", "rnd subfamily. rnd2 is constitutively", "subfamily. rnd2 is constitutively bound", "rnd2 is constitutively bound to", "is constitutively bound to gtp", "constitutively bound to gtp and", "bound to gtp and lacks", "to gtp and lacks gtpase", "gtp and lacks gtpase activity.", "and lacks gtpase activity. no", "lacks gtpase activity. no guanine", "gtpase activity. no guanine nucleotide", "activity. no guanine 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branching fujita et", "branching fujita et al.", "et al. 2002 kakimoto", "al. 2002 kakimoto et", "2002 kakimoto et al.", "et al. 2004 tanaka", "al. 2004 tanaka et", "2004 tanaka et al.", "et al. 2006 wakita", "al. 2006 wakita et", "2006 wakita et al.", "et al. 2011 and", "al. 2011 and migration", "2011 and migration of", "and migration of newborn neurons", "migration of newborn neurons within", "of newborn neurons within the", "newborn neurons within the embryonic", "neurons within the embryonic cerebral", "within the embryonic cerebral cortex", "embryonic cerebral cortex nakamura", "cerebral cortex nakamura et", "cortex nakamura et al.", "et al. 2006 heng", "al. 2006 heng et", "2006 heng et al.", "et al. 2008 alfano", "al. 2008 alfano et", "2008 alfano et al.", "et al. 2011 pacary", "al. 2011 pacary et", "2011 pacary et al.", "et al. 2011 gladwyn", "al. 2011 gladwyn ng", "2011 gladwyn ng et", "gladwyn ng et al. 2015", "et al. 2015 heng", "al. 2015 heng et", "2015 heng et al.", "heng et al. 2015 ." ] }, { "record_id": "GLY_000594_1_1918", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9696273", "r hsa", "hsa 9696273", "r hsa 9696273" ] }, { "record_id": "GLY_000594_1_1918", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rnd1 gtpase", "gtpase cycle", "rnd1 gtpase cycle", "rnd1 is", "is an", "an atypical", "atypical rho", "rho gtpase", "gtpase from", "from the", "the rnd", "rnd subfamily.", "subfamily. rnd1", "is constitutively", "constitutively bound", "bound to", "to gtp", "gtp and", "and lacks", "lacks gtpase", "gtpase activity.", "activity. no", "no guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "gtpase activator", "activator proteins", "or guanine", "nucleotide dissociation", "dissociation inhibitors", "act on", "on rnd1.", "rnd1. rnd1", "rnd1 localizes", "localizes to", "to the", "the plasma", "plasma membrane", "but can", "can be", "be 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"an oncogenic", "oncogenic role", "in some", "some cancer", "cancer types.", "types. rnd1", "rnd1 expression", "expression increases", "increases in", "in response", "response to", "to anti", "anti cancer", "cancer agents", "agents and", "and in", "in may", "may be", "be involved", "involved in", "in resistance", "resistance to", "to treatment.", "treatment. for", "for review", "please refer", "refer to", "to mouly", "mouly et", "et al.", "al. 2019.", "rnd1 is an", "is an atypical", "an atypical rho", "atypical rho gtpase", "rho gtpase from", "gtpase from the", "from the rnd", "the rnd subfamily.", "rnd subfamily. rnd1", "subfamily. rnd1 is", "rnd1 is constitutively", "is constitutively bound", "constitutively bound to", "bound to gtp", "to gtp and", "gtp and lacks", "and lacks gtpase", "lacks gtpase activity.", "gtpase activity. no", "activity. no guanine", "no guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factors", "factors gefs", "gtpase activator 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resistance to treatment.", "resistance to treatment. for", "to treatment. for review", "for review please", "review please refer", "please refer to mouly", "refer to mouly et", "to mouly et al.", "mouly et al. 2019.", "rnd1 is an atypical rho", "is an atypical rho gtpase", "an atypical rho gtpase from", "atypical rho gtpase from the", "rho gtpase from the rnd", "gtpase from the rnd subfamily.", "from the rnd subfamily. rnd1", "the rnd subfamily. rnd1 is", "rnd subfamily. rnd1 is constitutively", "subfamily. rnd1 is constitutively bound", "rnd1 is constitutively bound to", "is constitutively bound to gtp", "constitutively bound to gtp and", "bound to gtp and lacks", "to gtp and lacks gtpase", "gtp and lacks gtpase activity.", "and lacks gtpase activity. no", "lacks gtpase activity. no guanine", "gtpase activity. no guanine nucleotide", "activity. no guanine nucleotide exchange", "no guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "gefs gtpase activator", 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the phosphorylated", "binds the phosphorylated c terminal", "the phosphorylated c terminal region", "phosphorylated c terminal region of", "c terminal region of csf3r", "region of csf3r h\u00f6rtner", "of csf3r h\u00f6rtner et", "csf3r h\u00f6rtner et al.", "et al. 2002 van", "al. 2002 van de", "2002 van de geijn", "van de geijn et al.", "de geijn et al. 2004", "et al. 2004 and", "al. 2004 and inferred", "2004 and inferred from", "and inferred from mouse homologs", "from mouse homologs and", "mouse homologs and acts", "homologs and acts in", "and acts in two ways:", "acts in two ways: direct", "in two ways: direct inhibition", "two ways: direct inhibition of", "ways: direct inhibition of the", "direct inhibition of the phosphorylation", "inhibition of the phosphorylation activity", "of the phosphorylation activity of", "the phosphorylation activity of jak2", "activity of jak2 van", "of jak2 van de", "jak2 van de geijn", "al. 2004 and promotion", "2004 and promotion of", "promotion of endocytosis ward", "of endocytosis ward et", "endocytosis ward et al.", "et al. 1999 aarts", "al. 1999 aarts et", "1999 aarts et al.", "et al. 2004 irandoust", "al. 2004 irandoust et", "2004 irandoust et al.", "et al. 2007 and", "al. 2007 and ubiquitination", "and ubiquitination irandoust et", "ubiquitination irandoust et al.", "et al. 2007 w\u00f6lfler", "al. 2007 w\u00f6lfler et", "2007 w\u00f6lfler et al.", "et al. 2009 of", "al. 2009 of csf3r." ] }, { "record_id": "GLY_000594_1_1921", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9706369", "r hsa", "hsa 9706369", "r hsa 9706369" ] }, { "record_id": "GLY_000594_1_1921", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "negative regulation", "regulation of", "of flt3", "negative regulation of", "regulation of flt3", "negative regulation of flt3", "flt3 activity", "activity is", "is negatively", "negatively regulated", "regulated through", 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and", "in kazi and roonstrand", "and roonstrand 2019", "roonstrand 2019 .", "flt3 activity is negatively regulated", "activity is negatively regulated through", "is negatively regulated through several", "negatively regulated through several mechanisms", "regulated through several mechanisms including", "through several mechanisms including dephosphorylation", "mechanisms including dephosphorylation interaction", "including dephosphorylation interaction with", "dephosphorylation interaction with protein", "interaction with protein partners that", "with protein partners that limit", "protein partners that limit downstream", "partners that limit downstream signaling", "that limit downstream signaling pathways", "downstream signaling pathways and", "signaling pathways and by", "pathways and by ubiquitin", "and by ubiquitin mediated internalization", "by ubiquitin mediated internalization and", "ubiquitin mediated internalization and degradation", "internalization and degradation reviewed", "and degradation reviewed in", "degradation reviewed in kazi", "reviewed in kazi and roonstrand", "kazi and roonstrand 2019", "and roonstrand 2019 ." ] }, { "record_id": "GLY_000594_1_1922", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9707564", "r hsa", "hsa 9707564", "r hsa 9707564" ] }, { "record_id": "GLY_000594_1_1922", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cytoprotection by", "by hmox1", "cytoprotection by hmox1", "expression of", "of heme", "heme oxygenase", "oxygenase 1", "is regulated", "regulated by", "by various", "various indicators", "indicators of", "of cell", "cell stress", "while hmox2", "hmox2 is", "is expressed", "expressed constitutively.", "constitutively. both", "both catalyze", "catalyze the", "the breakdown", "breakdown of", "heme into", "into biliverdin", "carbon monoxide", "and ferrous", "ferrous iron.", "iron. biliverdin", "biliverdin is", "is immediately", "immediately reduced", "reduced to", "to bilirubin", "bil .", ". both", "both bilirubin", "bilirubin and", "and carbon", "monoxide can", "can localize", "localize to", "to different", "different compartments", "compartments and", "and outside", "outside the", "the cell.", "cell. cytoprotection", "hmox1 is", "is exerted", "exerted directly", "directly by", "hmox1 and", "and by", "by the", "the antioxidant", "antioxidant metabolites", "metabolites produced", "produced through", "through the", "the degradation", "degradation of", "of heme.", "heme. additionally", "due to", "to the", "the reactive", "reactive nature", "nature of", "of labile", "labile heme", "its degradation", "degradation is", "is intrinsically", "intrinsically protective.

              hmox1", "protective.

              hmox1 confers", "confers cytoprotection", "cytoprotection against", "against cell", "cell death", "death in", "in various", "various models", "models of", "of lung", "lung and", "and vascular", "vascular injury", "injury by", "by inhibiting", "inhibiting apoptosis", "and immune", "immune cell", "cell proliferation.", "proliferation. it", "it binds", "binds to", "the nacht", "nacht domain", "domain of", "of nlrp3", "nlrp3 inflammasome", "blocking its", "its activation.", "activation. in", "in mouse", "mouse it", "it directly", "directly binds", "binds stat3", "stat3 to", "to control", "control the", "the generation", "generation of", "of pathogenic", "pathogenic th17", "th17 cells", "cells during", "during neutrophilic", "neutrophilic airway", "airway inflammation.", "inflammation. it", "it also", "also blocks", "blocks phosphorylation", "phosphorylation of", "of stat3", "stat3 by", "by ptk6", "ptk6 and", "and co", "co inhibits", "inhibits socs3", "a negative", "negative feedback", "feedback factor", "factor of", "stat3 activation", "as well", "well as", "as ror\u03b3t", "thereby decreasing", "decreasing th2", "th2 and", "and th17", "th17 immune", "immune responses", "and alleviating", "alleviating airway", "airway inflammation.

              the", "inflammation.

              the beneficial", "beneficial effects", "effects of", "of the", "the three", "three products", "products generated", "generated by", "hmox1 differ", "differ not", "not only", "only in", "in their", "their inherent", "inherent molecular", "molecular mechanisms", "but also", "also in", "their downstream", "downstream cellular", "cellular targets.", "targets. to", "to date", "this is", "is the", "the only", "only enzymatic", "enzymatic system", "system known", "known to", "to exhibit", "exhibit such", "such characteristics.", "characteristics. iron", "iron is", "is a", "a vital", "vital component", "component of", "of many", "many biological", "biological systems", "systems and", "and is", "is capable", "capable of", "of producing", "producing hydroxyl", "hydroxyl radicals", "radicals via", "via fenton", "fenton chemistry.", "chemistry. for", "for this", "this reason", "is sequestered", "sequestered by", "the storage", "storage multimer", "multimer ferritin", "ferritin and", "and to", "to prevent", "prevent oxidative", "oxidative damage", "damage while", "while maintaining", "maintaining the", "the iron", "iron pool.", "pool. on", "on the", "the other", "other hand", "the protective", "protective effects", "of bilirubin", "co are", "are broadly", "broadly recognized", "which has", "has led", "led to", "to their", "their consideration", "consideration as", "as therapeutics", "therapeutics for", "for a", "a range", "range of", "of diseases.", "diseases. bilirubin", "bilirubin has", "has been", "been recognized", "recognized as", "as one", "one of", "the most", "most potent", "potent antioxidants", "antioxidants in", "in nature", "and moderate", "moderate increases", "increases of", "of its", "its serum", "serum level", "level have", "have been", "been shown", "shown in", "in numerous", "numerous large", "large scale", "scale population", "population and", "and epidemiological", "epidemiological studies", "studies to", "to have", "have a", "a protective", "protective effect", "effect against", "against cardiovascular", "cardiovascular and", "and metabolic", "metabolic disease.", "disease. these", "these effects", "effects are", "are mediated", "mediated by", "by bilirubin", "bilirubin scavenging", "scavenging of", "of superoxide", "superoxide anions", "anions and", "and reactive", "reactive nitrogen", "nitrogen species", "by activating", "activating the", "the transcription", "transcription factor", "factor ppar", "ppar alpha.

              co", "alpha.

              co and", "and biliverdin/bilirubin", "shown to", "to exert", "exert protective", "effects in", "in the", "the liver", "liver against", "against a", "a number", "number of", "of stimuli", "as in", "in chronic", "chronic hepatitis", "hepatitis c", "c and", "and in", "in transplanted", "transplanted liver", "liver grafts.", "grafts. co", "co possesses", "possesses intriguing", "intriguing signaling", "signaling properties", "properties affecting", "affecting numerous", "numerous critical", "critical cellular", "cellular functions", "functions including", "including but", "but not", "not limited", "limited to", "to inflammation", "cellular proliferation", "and apoptotic", "apoptotic cell", "cell death.", "death. binding", "binding of", "of co", "co with", "with key", "key ferrous", "ferrous hemoproteins", "hemoproteins serves", "serves as", "as a", "a posttranslational", "posttranslational modification", "modification that", "that regulates", "regulates important", "important processes", "processes as", "as diverse", "diverse as", "as aerobic", "aerobic metabolism", "oxidative stress", "and mitochondrial", "mitochondrial bioenergetics.", "bioenergetics. the", "most important", "important of", "of these", "these is", "the mitochondrial", "mitochondrial cytochrome", "cytochrome c", "c oxidase", "cco .", ". by", "by locally", "locally blocking", "blocking mitochondrial", "mitochondrial respiration", "respiration the", "the main", "main source", "source of", "of reactive", "reactive oxygen", "oxygen species", "the cell", "cell is", "is switched", "switched off.", "off. additionally", "additionally co", "co enables", "enables efficient", "efficient reduction", "reduction of", "of methemoglobin", "by h2o2", "thus preventing", "preventing the", "of free", "free heme", "heme in", "in hemorrhagic", "hemorrhagic diseases", "diseases and", "and malaria", "origassa and", "and c\u00e2mara", "morse et", "et al", "ryter et", "cooper and", "and brown", "hinds and", "and stec", "2008 .", "expression of heme", "of heme oxygenase", "heme oxygenase 1", "1 hmox1", "is regulated by", "regulated by various", "by various indicators", "various indicators of", "indicators of cell", "of cell stress", "stress while", "while hmox2 is", "hmox2 is expressed", "is expressed constitutively.", "expressed constitutively. both", "constitutively. both catalyze", "both catalyze the", "catalyze the breakdown", "the breakdown of", "breakdown of heme", "of heme into", "heme into biliverdin", "biliverdin bv", "monoxide co", "and ferrous iron.", "ferrous iron. biliverdin", "iron. biliverdin is", "biliverdin is immediately", "is immediately reduced", "immediately reduced to", "reduced to bilirubin", "bilirubin bil", "bil . both", ". both bilirubin", "both bilirubin and", "bilirubin and carbon", "and carbon monoxide", "carbon monoxide can", "monoxide can localize", "can localize to", "localize to different", "to different compartments", "different compartments and", "compartments and outside", "and outside the", "outside the cell.", "the cell. cytoprotection", "cell. cytoprotection by", "by hmox1 is", "hmox1 is exerted", "is exerted directly", "exerted directly by", "directly by hmox1", "by hmox1 and", "hmox1 and by", "and by the", "by the antioxidant", "the antioxidant metabolites", "antioxidant metabolites produced", "metabolites produced through", "produced through the", "through the degradation", "the degradation of", "degradation of heme.", "of heme. additionally", "additionally due", "due to the", "to the reactive", "the reactive nature", "reactive nature of", "nature of labile", "of labile heme", "heme its", "its degradation is", "degradation is intrinsically", "is intrinsically protective.

              hmox1", "intrinsically protective.

              hmox1 confers", "protective.

              hmox1 confers cytoprotection", "confers cytoprotection against", "cytoprotection against cell", "against cell death", "cell death in", "death in various", "in various models", "various models of", "models of lung", "of lung and", "lung and vascular", "and vascular injury", "vascular injury by", "injury by inhibiting", "by inhibiting apoptosis", "apoptosis inflammation", "inflammation and", "and immune cell", "immune cell proliferation.", "cell proliferation. it", "proliferation. it binds", "it binds to", "binds to the", "to the nacht", "the nacht domain", "nacht domain of", "domain of nlrp3", "of nlrp3 inflammasome", "inflammasome blocking", "blocking its activation.", "its activation. in", "activation. in mouse", "in mouse it", "mouse it directly", "it directly binds", "directly binds stat3", "binds stat3 to", "stat3 to control", "to control the", "control the generation", "the generation of", "generation of pathogenic", "of pathogenic th17", "pathogenic th17 cells", "th17 cells during", "cells during neutrophilic", "during neutrophilic airway", "neutrophilic airway inflammation.", "airway inflammation. it", "inflammation. it also", "it also blocks", "also blocks phosphorylation", "blocks phosphorylation of", "phosphorylation of stat3", "of stat3 by", "stat3 by ptk6", "by ptk6 and", "ptk6 and co", "and co inhibits", "co inhibits socs3", "socs3 a", "a negative feedback", "negative feedback factor", "feedback factor of", "factor of stat3", "of stat3 activation", "activation as", "as well as", "well as ror\u03b3t", "ror\u03b3t thereby", "thereby decreasing th2", "decreasing th2 and", "th2 and th17", "and th17 immune", "th17 immune responses", "responses and", "and alleviating airway", "alleviating airway inflammation.

              the", "airway inflammation.

              the beneficial", "inflammation.

              the beneficial effects", "beneficial effects of", "effects of the", "of the three", "the three products", "three products generated", "products generated by", "generated by hmox1", "by hmox1 differ", "hmox1 differ not", "differ not only", "not only in", "only in their", "in their inherent", "their inherent molecular", "inherent molecular mechanisms", "mechanisms but", "but also in", "also in their", "in their downstream", "their downstream cellular", "downstream cellular targets.", "cellular targets. to", "targets. to date", "date this", "this is the", "is the only", "the only enzymatic", "only enzymatic system", "enzymatic system known", "system known to", "known to exhibit", "to exhibit such", "exhibit such characteristics.", "such characteristics. iron", "characteristics. iron is", "iron is a", "is a vital", "a vital component", "vital component of", "component of many", "of many biological", "many biological systems", "biological systems and", "systems and is", "and is capable", "is capable of", "capable of producing", "of producing hydroxyl", "producing hydroxyl radicals", "hydroxyl radicals via", "radicals via fenton", "via fenton chemistry.", "fenton chemistry. for", "chemistry. for this", "for this reason", "reason iron", "iron is sequestered", "is sequestered by", "sequestered by the", "by the storage", "the storage multimer", "storage multimer ferritin", "multimer ferritin and", "ferritin and to", "and to prevent", "to prevent oxidative", "prevent oxidative damage", "oxidative damage while", "damage while maintaining", "while maintaining the", "maintaining the iron", "the iron pool.", "iron pool. on", "pool. on the", "on the other", "the other hand", "hand the", "the protective effects", "protective effects of", "effects of bilirubin", "of bilirubin and", "bilirubin and co", "and co are", "co are broadly", "are broadly recognized", "recognized which", "which has led", "has led to", "led to their", "to their consideration", "their consideration as", "consideration as therapeutics", "as therapeutics for", "therapeutics for a", "for a range", "a range of", "range of diseases.", "of diseases. bilirubin", "diseases. bilirubin has", "bilirubin has been", "has been recognized", "been recognized as", "recognized as one", "as one of", "one of the", "of the most", "the most potent", "most potent antioxidants", "potent antioxidants in", "antioxidants in nature", "nature and", "and moderate increases", "moderate increases of", "increases of its", "of its serum", "its serum level", "serum level have", "level have been", "have been shown", "been shown in", "shown in numerous", "in numerous large", "numerous large scale", "large scale population", "scale population and", "population and epidemiological", "and epidemiological studies", "epidemiological studies to", "studies to have", "to have a", "have a protective", "a protective effect", "protective effect against", "effect against cardiovascular", "against cardiovascular and", "cardiovascular and metabolic", "and metabolic disease.", "metabolic disease. these", "disease. these effects", "these effects are", "effects are mediated", "are mediated by", "mediated by bilirubin", "by bilirubin scavenging", "bilirubin scavenging of", "scavenging of superoxide", "of superoxide anions", "superoxide anions and", "anions and reactive", "and reactive nitrogen", "reactive nitrogen species", "species rns", "and by activating", "by activating the", "activating the transcription", "the transcription factor", "transcription factor ppar", "factor ppar alpha.

              co", "ppar alpha.

              co and", "alpha.

              co and biliverdin/bilirubin", "biliverdin/bilirubin have", "been shown to", "shown to exert", "to exert protective", "exert protective effects", "protective effects in", "effects in the", "in the liver", "the liver against", "liver against a", "against a number", "a number of", "number of stimuli", "stimuli as", "as in chronic", "in chronic hepatitis", "chronic hepatitis c", "hepatitis c and", "c and in", "and in transplanted", "in transplanted liver", "transplanted liver grafts.", "liver grafts. co", "grafts. co possesses", "co possesses intriguing", "possesses intriguing signaling", "intriguing signaling properties", "signaling properties affecting", "properties affecting numerous", "affecting numerous critical", "numerous critical cellular", "critical cellular functions", "cellular functions including", "functions including but", "including but not", "but not limited", "not limited to", "limited to inflammation", "inflammation cellular", "proliferation and", "and apoptotic cell", "apoptotic cell death.", "cell death. binding", "death. binding of", "binding of co", "of co with", "co with key", "with key ferrous", "key ferrous hemoproteins", "ferrous hemoproteins serves", "hemoproteins serves as", "serves as a", "as a posttranslational", "a posttranslational modification", "posttranslational modification that", "modification that regulates", "that regulates important", "regulates important processes", "important processes as", "processes as diverse", "as diverse as", "diverse as aerobic", "as aerobic metabolism", "metabolism oxidative", "stress and", "and mitochondrial bioenergetics.", "mitochondrial bioenergetics. the", "bioenergetics. the most", "the most important", "most important of", "important of these", "of these is", "these is the", "is the mitochondrial", "the mitochondrial cytochrome", "mitochondrial cytochrome c", "cytochrome c oxidase", "oxidase cco", "cco . by", ". by locally", "by locally blocking", "locally blocking mitochondrial", "blocking mitochondrial respiration", "mitochondrial respiration the", "respiration the main", "the main source", "main source of", "source of reactive", "of reactive oxygen", "reactive oxygen species", "species ros", "ros in", "in the cell", "the cell is", "cell is switched", "is switched off.", "switched off. additionally", "off. additionally co", "additionally co enables", "co enables efficient", "enables efficient reduction", "efficient reduction of", "reduction of methemoglobin", "methemoglobin methb", "methb by", "h2o2 thus", "thus preventing the", "preventing the generation", "generation of free", "of free heme", "free heme in", "heme in hemorrhagic", "in hemorrhagic diseases", "hemorrhagic diseases and", "diseases and malaria", "malaria origassa", "origassa and c\u00e2mara", "c\u00e2mara 2013", "2013 morse", "morse et al", "al 2009", "2009 ryter", "ryter et al", "al 2006", "2006 cooper", "cooper and brown", "brown 2008", "2008 hinds", "hinds and stec", "stec 2008", "expression of heme oxygenase", "of heme oxygenase 1", "oxygenase 1 hmox1", "hmox1 is regulated", "is regulated by various", "regulated by various indicators", "by various indicators of", "various indicators of cell", "indicators of cell stress", "cell stress while", "stress while hmox2", "while hmox2 is expressed", "hmox2 is expressed constitutively.", "is expressed constitutively. both", "expressed constitutively. both catalyze", "constitutively. both catalyze the", "both catalyze the breakdown", "catalyze the breakdown of", "the breakdown of heme", "breakdown of heme into", "of heme into biliverdin", "into biliverdin bv", "bv carbon", "carbon monoxide co", "co and", "and ferrous iron. biliverdin", "ferrous iron. biliverdin is", "iron. biliverdin is immediately", "biliverdin is immediately reduced", "is immediately reduced to", "immediately reduced to bilirubin", "to bilirubin bil", "bilirubin bil .", "bil . both bilirubin", ". both bilirubin and", "both bilirubin and carbon", "bilirubin and carbon monoxide", "and carbon monoxide can", "carbon monoxide can localize", "monoxide can localize to", "can localize to different", "localize to different compartments", "to different compartments and", "different compartments and outside", "compartments and outside the", "and outside the cell.", "outside the cell. cytoprotection", "the cell. cytoprotection by", "cell. cytoprotection by hmox1", "cytoprotection by hmox1 is", "by hmox1 is exerted", "hmox1 is exerted directly", "is exerted directly by", "exerted directly by hmox1", "directly by hmox1 and", "by hmox1 and by", "hmox1 and by the", "and by the antioxidant", "by the antioxidant metabolites", "the antioxidant metabolites produced", "antioxidant metabolites produced through", "metabolites produced through the", "produced through the degradation", "through the degradation of", "the degradation of heme.", "degradation of heme. additionally", "heme. additionally due", "additionally due to", "due to the reactive", "to the reactive nature", "the reactive nature of", "reactive nature of labile", "nature of labile heme", "labile heme its", "heme its degradation", "its degradation is intrinsically", "degradation is intrinsically protective.

              hmox1", "is intrinsically protective.

              hmox1 confers", "intrinsically protective.

              hmox1 confers cytoprotection", "protective.

              hmox1 confers cytoprotection against", "confers cytoprotection against cell", "cytoprotection against cell death", "against cell death in", "cell death in various", "death in various models", "in various models of", "various models of lung", "models of lung and", "of lung and vascular", "lung and vascular injury", "and vascular injury by", "vascular injury by inhibiting", "injury by inhibiting apoptosis", "inhibiting apoptosis inflammation", "inflammation and immune", "and immune cell proliferation.", "immune cell proliferation. it", "cell proliferation. it binds", "proliferation. it binds to", "it binds to the", "binds to the nacht", "to the nacht domain", "the nacht domain of", "nacht domain of nlrp3", "domain of nlrp3 inflammasome", "nlrp3 inflammasome blocking", "inflammasome blocking its", "blocking its activation. in", "its activation. in mouse", "activation. in mouse it", "in mouse it directly", "mouse it directly binds", "it directly binds stat3", "directly binds stat3 to", "binds stat3 to control", "stat3 to control the", "to control the generation", "control the generation of", "the generation of pathogenic", "generation of pathogenic th17", "of pathogenic th17 cells", "pathogenic th17 cells during", "th17 cells during neutrophilic", "cells during neutrophilic airway", "during neutrophilic airway inflammation.", "neutrophilic airway inflammation. it", "airway inflammation. it also", "inflammation. it also blocks", "it also blocks phosphorylation", "also blocks phosphorylation of", "blocks phosphorylation of stat3", "phosphorylation of stat3 by", "of stat3 by ptk6", "stat3 by ptk6 and", "by ptk6 and co", "ptk6 and co inhibits", "and co inhibits socs3", "inhibits socs3 a", "socs3 a negative", "a negative feedback factor", "negative feedback factor of", "feedback factor of stat3", "factor of stat3 activation", "stat3 activation as", "activation as well", "as well as ror\u03b3t", "as ror\u03b3t thereby", "ror\u03b3t thereby decreasing", "thereby decreasing th2 and", "decreasing th2 and th17", "th2 and th17 immune", "and th17 immune responses", "immune responses and", "responses and alleviating", "and alleviating airway inflammation.

              the", "alleviating airway inflammation.

              the beneficial", "airway inflammation.

              the beneficial effects", "inflammation.

              the beneficial effects of", "beneficial effects of the", "effects of the three", "of the three products", "the three products generated", "three products generated by", "products generated by hmox1", "generated by hmox1 differ", "by hmox1 differ not", "hmox1 differ not only", "differ not only in", "not only in their", "only in their inherent", "in their inherent molecular", "their inherent molecular mechanisms", "molecular mechanisms but", "mechanisms but also", "but also in their", "also in their downstream", "in their downstream cellular", "their downstream cellular targets.", "downstream cellular targets. to", "cellular targets. to date", "to date this", "date this is", "this is the only", "is the only enzymatic", "the only enzymatic system", "only enzymatic system known", "enzymatic system known to", "system known to exhibit", "known to exhibit such", "to exhibit such characteristics.", "exhibit such characteristics. iron", "such characteristics. iron is", "characteristics. iron is a", "iron is a vital", "is a vital component", "a vital component of", "vital component of many", "component of many biological", "of many biological systems", "many biological systems and", "biological systems and is", "systems and is capable", "and is capable of", "is capable of producing", "capable of producing hydroxyl", "of producing hydroxyl radicals", "producing hydroxyl radicals via", "hydroxyl radicals via fenton", "radicals via fenton chemistry.", "via fenton chemistry. for", "fenton chemistry. for this", "chemistry. for this reason", "this reason iron", "reason iron is", "iron is sequestered by", "is sequestered by the", "sequestered by the storage", "by the storage multimer", "the storage multimer ferritin", "storage multimer ferritin and", "multimer ferritin and to", "ferritin and to prevent", "and to prevent oxidative", "to prevent oxidative damage", "prevent oxidative damage while", "oxidative damage while maintaining", "damage while maintaining the", "while maintaining the iron", "maintaining the iron pool.", "the iron pool. on", "iron pool. on the", "pool. on the other", "on the other hand", "other hand the", "hand the protective", "the protective effects of", "protective effects of bilirubin", "effects of bilirubin and", "of bilirubin and co", "bilirubin and co are", "and co are broadly", "co are broadly recognized", "broadly recognized which", "recognized which has", "which has led to", "has led to their", "led to their consideration", "to their consideration as", "their consideration as therapeutics", "consideration as therapeutics for", "as therapeutics for a", "therapeutics for a range", "for a range of", "a range of diseases.", "range of diseases. bilirubin", "of diseases. bilirubin has", "diseases. bilirubin has been", "bilirubin has been recognized", "has been recognized as", "been recognized as one", "recognized as one of", "as one of the", "one of the most", "of the most potent", "the most potent antioxidants", "most potent antioxidants in", "potent antioxidants in nature", "in nature and", "nature and moderate", "and moderate increases of", "moderate increases of its", "increases of its serum", "of its serum level", "its serum level have", "serum level have been", "level have been shown", "have been shown in", "been shown in numerous", "shown in numerous large", "in numerous large scale", "numerous large scale population", "large scale population and", "scale population and epidemiological", "population and epidemiological studies", "and epidemiological studies to", "epidemiological studies to have", "studies to have a", "to have a protective", "have a protective effect", "a protective effect against", "protective effect against cardiovascular", "effect against cardiovascular and", "against cardiovascular and metabolic", "cardiovascular and metabolic disease.", "and metabolic disease. these", "metabolic disease. these effects", "disease. these effects are", "these effects are mediated", "effects are mediated by", "are mediated by bilirubin", "mediated by bilirubin scavenging", "by bilirubin scavenging of", "bilirubin scavenging of superoxide", "scavenging of superoxide anions", "of superoxide anions and", "superoxide anions and reactive", "anions and reactive nitrogen", "and reactive nitrogen species", "nitrogen species rns", "rns and", "and by activating the", "by activating the transcription", "activating the transcription factor", "the transcription factor ppar", "transcription factor ppar alpha.

              co", "factor ppar alpha.

              co and", "ppar alpha.

              co and biliverdin/bilirubin", "and biliverdin/bilirubin have", "biliverdin/bilirubin have been", "have been shown to", "been shown to exert", "shown to exert protective", "to exert protective effects", "exert protective effects in", "protective effects in the", "effects in the liver", "in the liver against", "the liver against a", "liver against a number", "against a number of", "a number of stimuli", "of stimuli as", "stimuli as in", "as in chronic hepatitis", "in chronic hepatitis c", "chronic hepatitis c and", "hepatitis c and in", "c and in transplanted", "and in transplanted liver", "in transplanted liver grafts.", "transplanted liver grafts. co", "liver grafts. co possesses", "grafts. co possesses intriguing", "co possesses intriguing signaling", "possesses intriguing signaling properties", "intriguing signaling properties affecting", "signaling properties affecting numerous", "properties affecting numerous critical", "affecting numerous critical cellular", "numerous critical cellular functions", "critical cellular functions including", "cellular functions including but", "functions including but not", "including but not limited", "but not limited to", "not limited to inflammation", "to inflammation cellular", "inflammation cellular proliferation", "cellular proliferation and", "proliferation and apoptotic", "and apoptotic cell death.", "apoptotic cell death. binding", "cell death. binding of", "death. binding of co", "binding of co with", "of co with key", "co with key ferrous", "with key ferrous hemoproteins", "key ferrous hemoproteins serves", "ferrous hemoproteins serves as", "hemoproteins serves as a", "serves as a posttranslational", "as a posttranslational modification", "a posttranslational modification that", "posttranslational modification that regulates", "modification that regulates important", "that regulates important processes", "regulates important processes as", "important processes as diverse", "processes as diverse as", "as diverse as aerobic", "diverse as aerobic metabolism", "aerobic metabolism oxidative", "metabolism oxidative stress", "oxidative stress and", "stress and mitochondrial", "and mitochondrial bioenergetics. the", "mitochondrial bioenergetics. the most", "bioenergetics. the most important", "the most important of", "most important of these", "important of these is", "of these is the", "these is the mitochondrial", "is the mitochondrial cytochrome", "the mitochondrial cytochrome c", "mitochondrial cytochrome c oxidase", "c oxidase cco", "oxidase cco .", "cco . by locally", ". by locally blocking", "by locally blocking mitochondrial", "locally blocking mitochondrial respiration", "blocking mitochondrial respiration the", "mitochondrial respiration the main", "respiration the main source", "the main source of", "main source of reactive", "source of reactive oxygen", "of reactive oxygen species", "oxygen species ros", "ros in the", "in the cell is", "the cell is switched", "cell is switched off.", "is switched off. additionally", "switched off. additionally co", "off. additionally co enables", "additionally co enables efficient", "co enables efficient reduction", "enables efficient reduction of", "efficient reduction of methemoglobin", "of methemoglobin methb", "methb by h2o2", "by h2o2 thus", "h2o2 thus preventing", "thus preventing the generation", "preventing the generation of", "the generation of free", "generation of free heme", "of free heme in", "free heme in hemorrhagic", "heme in hemorrhagic diseases", "in hemorrhagic diseases and", "hemorrhagic diseases and malaria", "and malaria origassa", "malaria origassa and", "and c\u00e2mara 2013", "2013 morse et", "et al 2009", "2009 ryter et", "et al 2006", "2006 cooper and", "and brown 2008", "2008 hinds and", "and stec 2008", "stec 2008 .", "expression of heme oxygenase 1", "heme oxygenase 1 hmox1", "1 hmox1 is", "hmox1 is regulated by", "is regulated by various indicators", "regulated by various indicators of", "by various indicators of cell", "various indicators of cell stress", "of cell stress while", "cell stress while hmox2", "stress while hmox2 is", "while hmox2 is expressed constitutively.", "hmox2 is expressed constitutively. both", "is expressed constitutively. both catalyze", "expressed constitutively. both catalyze the", "constitutively. both catalyze the breakdown", "both catalyze the breakdown of", "catalyze the breakdown of heme", "the breakdown of heme into", "breakdown of heme into biliverdin", "heme into biliverdin bv", "bv carbon monoxide", "co and ferrous", "and ferrous iron. biliverdin is", "ferrous iron. biliverdin is immediately", "iron. biliverdin is immediately reduced", "biliverdin is immediately reduced to", "is immediately reduced to bilirubin", "reduced to bilirubin bil", "to bilirubin bil .", "bilirubin bil . both", "bil . both bilirubin and", ". both bilirubin and carbon", "both bilirubin and carbon monoxide", "bilirubin and carbon monoxide can", "and carbon monoxide can localize", "carbon monoxide can localize to", "monoxide can localize to different", "can localize to different compartments", "localize to different compartments and", "to different compartments and outside", "different compartments and outside the", "compartments and outside the cell.", "and outside the cell. cytoprotection", "outside the cell. cytoprotection by", "the cell. cytoprotection by hmox1", "cell. cytoprotection by hmox1 is", "cytoprotection by hmox1 is exerted", "by hmox1 is exerted directly", "hmox1 is exerted directly by", "is exerted directly by hmox1", "exerted directly by hmox1 and", "directly by hmox1 and by", "by hmox1 and by the", "hmox1 and by the antioxidant", "and by the antioxidant metabolites", "by the antioxidant metabolites produced", "the antioxidant metabolites produced through", "antioxidant metabolites produced through the", "metabolites produced through the degradation", "produced through the degradation of", "through the degradation of heme.", "the degradation of heme. additionally", "of heme. additionally due", "heme. additionally due to", "additionally due to the", "due to the reactive nature", "to the reactive nature of", "the reactive nature of labile", "reactive nature of labile heme", "of labile heme its", "labile heme its degradation", "heme its degradation is", "its degradation is intrinsically protective.

              hmox1", "degradation is intrinsically protective.

              hmox1 confers", "is intrinsically protective.

              hmox1 confers cytoprotection", "intrinsically protective.

              hmox1 confers cytoprotection against", "protective.

              hmox1 confers cytoprotection against cell", "confers cytoprotection against cell death", "cytoprotection against cell death in", "against cell death in various", "cell death in various models", "death in various models of", "in various models of lung", "various models of lung and", "models of lung and vascular", "of lung and vascular injury", "lung and vascular injury by", "and vascular injury by inhibiting", "vascular injury by inhibiting apoptosis", "by inhibiting apoptosis inflammation", "apoptosis inflammation and", "inflammation and immune cell", "and immune cell proliferation. it", "immune cell proliferation. it binds", "cell proliferation. it binds to", "proliferation. it binds to the", "it binds to the nacht", "binds to the nacht domain", "to the nacht domain of", "the nacht domain of nlrp3", "nacht domain of nlrp3 inflammasome", "of nlrp3 inflammasome blocking", "nlrp3 inflammasome blocking its", "inflammasome blocking its activation.", "blocking its activation. in mouse", "its activation. in mouse it", "activation. in mouse it directly", "in mouse it directly binds", "mouse it directly binds stat3", "it directly binds stat3 to", "directly binds stat3 to control", "binds stat3 to control the", "stat3 to control the generation", "to control the generation of", "control the generation of pathogenic", "the generation of pathogenic th17", "generation of pathogenic th17 cells", "of pathogenic th17 cells during", "pathogenic th17 cells during neutrophilic", "th17 cells during neutrophilic airway", "cells during neutrophilic airway inflammation.", "during neutrophilic airway inflammation. it", "neutrophilic airway inflammation. it also", "airway inflammation. it also blocks", "inflammation. it also blocks phosphorylation", "it also blocks phosphorylation of", "also blocks phosphorylation of stat3", "blocks phosphorylation of stat3 by", "phosphorylation of stat3 by ptk6", "of stat3 by ptk6 and", "stat3 by ptk6 and co", "by ptk6 and co inhibits", "ptk6 and co inhibits socs3", "co inhibits socs3 a", "inhibits socs3 a negative", "socs3 a negative feedback", "a negative feedback factor of", "negative feedback factor of stat3", "feedback factor of stat3 activation", "of stat3 activation as", "stat3 activation as well", "activation as well as", "well as ror\u03b3t thereby", "as ror\u03b3t thereby decreasing", "ror\u03b3t thereby decreasing th2", "thereby decreasing th2 and th17", "decreasing th2 and th17 immune", "th2 and th17 immune responses", "th17 immune responses and", "immune responses and alleviating", "responses and alleviating airway", "and alleviating airway inflammation.

              the beneficial", "alleviating airway inflammation.

              the beneficial effects", "airway inflammation.

              the beneficial effects of", "inflammation.

              the beneficial effects of the", "beneficial effects of the three", "effects of the three products", "of the three products generated", "the three products generated by", "three products generated by hmox1", "products generated by hmox1 differ", "generated by hmox1 differ not", "by hmox1 differ not only", "hmox1 differ not only in", "differ not only in their", "not only in their inherent", "only in their inherent molecular", "in their inherent molecular mechanisms", "inherent molecular mechanisms but", "molecular mechanisms but also", "mechanisms but also in", "but also in their downstream", "also in their downstream cellular", "in their downstream cellular targets.", "their downstream cellular targets. to", "downstream cellular targets. to date", "targets. to date this", "to date this is", "date this is the", "this is the only enzymatic", "is the only enzymatic system", "the only enzymatic system known", "only enzymatic system known to", "enzymatic system known to exhibit", "system known to exhibit such", "known to exhibit such characteristics.", "to exhibit such characteristics. iron", "exhibit such characteristics. iron is", "such characteristics. iron is a", "characteristics. iron is a vital", "iron is a vital component", "is a vital component of", "a vital component of many", "vital component of many biological", "component of many biological systems", "of many biological systems and", "many biological systems and is", "biological systems and is capable", "systems and is capable of", "and is capable of producing", "is capable of producing hydroxyl", "capable of producing hydroxyl radicals", "of producing hydroxyl radicals via", "producing hydroxyl radicals via fenton", "hydroxyl radicals via fenton chemistry.", "radicals via fenton chemistry. for", "via fenton chemistry. for this", "fenton chemistry. for this reason", "for this reason iron", "this reason iron is", "reason iron is sequestered", "iron is sequestered by the", "is sequestered by the storage", "sequestered by the storage multimer", "by the storage multimer ferritin", "the storage multimer ferritin and", "storage multimer ferritin and to", "multimer ferritin and to prevent", "ferritin and to prevent oxidative", "and to prevent oxidative damage", "to prevent oxidative damage while", "prevent oxidative damage while maintaining", "oxidative damage while maintaining the", "damage while maintaining the iron", "while maintaining the iron pool.", "maintaining the iron pool. on", "the iron pool. on the", "iron pool. on the other", "pool. on the other hand", "the other hand the", "other hand the protective", "hand the protective effects", "the protective effects of bilirubin", "protective effects of bilirubin and", "effects of bilirubin and co", "of bilirubin and co are", "bilirubin and co are broadly", "and co are broadly recognized", "are broadly recognized which", "broadly recognized which has", "recognized which has led", "which has led to their", "has led to their consideration", "led to their consideration as", "to their consideration as therapeutics", "their consideration as therapeutics for", "consideration as therapeutics for a", "as therapeutics for a range", "therapeutics for a range of", "for a range of diseases.", "a range of diseases. bilirubin", "range of diseases. bilirubin has", "of diseases. bilirubin has been", "diseases. bilirubin has been recognized", "bilirubin has been recognized as", "has been recognized as one", "been recognized as one of", "recognized as one of the", "as one of the most", "one of the most potent", "of the most potent antioxidants", "the most potent antioxidants in", "most potent antioxidants in nature", "antioxidants in nature and", "in nature and moderate", "nature and moderate increases", "and moderate increases of its", "moderate increases of its serum", "increases of its serum level", "of its serum level have", "its serum level have been", "serum level have been shown", "level have been shown in", "have been shown in numerous", "been shown in numerous large", "shown in numerous large scale", "in numerous large scale population", "numerous large scale population and", "large scale population and epidemiological", "scale population and epidemiological studies", "population and epidemiological studies to", "and epidemiological studies to have", "epidemiological studies to have a", "studies to have a protective", "to have a protective effect", "have a protective effect against", "a protective effect against cardiovascular", "protective effect against cardiovascular and", "effect against cardiovascular and metabolic", "against cardiovascular and metabolic disease.", "cardiovascular and metabolic disease. these", "and metabolic disease. these effects", "metabolic disease. these effects are", "disease. these effects are mediated", "these effects are mediated by", "effects are mediated by bilirubin", "are mediated by bilirubin scavenging", "mediated by bilirubin scavenging of", "by bilirubin scavenging of superoxide", "bilirubin scavenging of superoxide anions", "scavenging of superoxide anions and", "of superoxide anions and reactive", "superoxide anions and reactive nitrogen", "anions and reactive nitrogen species", "reactive nitrogen species rns", "rns and by", "and by activating the transcription", "by activating the transcription factor", "activating the transcription factor ppar", "the transcription factor ppar alpha.

              co", "transcription factor ppar alpha.

              co and", "factor ppar alpha.

              co and biliverdin/bilirubin", "alpha.

              co and biliverdin/bilirubin have", "and biliverdin/bilirubin have been", "biliverdin/bilirubin have been shown", "have been shown to exert", "been shown to exert protective", "shown to exert protective effects", "to exert protective effects in", "exert protective effects in the", "protective effects in the liver", "effects in the liver against", "in the liver against a", "the liver against a number", "liver against a number of", "against a number of stimuli", "number of stimuli as", "of stimuli as in", "stimuli as in chronic", "as in chronic hepatitis c", "in chronic hepatitis c and", "chronic hepatitis c and in", "hepatitis c and in transplanted", "c and in transplanted liver", "and in transplanted liver grafts.", "in transplanted liver grafts. co", "transplanted liver grafts. co possesses", "liver grafts. co possesses intriguing", "grafts. co possesses intriguing signaling", "co possesses intriguing signaling properties", "possesses intriguing signaling properties affecting", "intriguing signaling properties affecting numerous", "signaling properties affecting numerous critical", "properties affecting numerous critical cellular", "affecting numerous critical cellular functions", "numerous critical cellular functions including", "critical cellular functions including but", "cellular functions including but not", "functions including but not limited", "including but not limited to", "but not limited to inflammation", "limited to inflammation cellular", "to inflammation cellular proliferation", "cellular proliferation and apoptotic", "proliferation and apoptotic cell", "and apoptotic cell death. binding", "apoptotic cell death. binding of", "cell death. binding of co", "death. binding of co with", "binding of co with key", "of co with key ferrous", "co with key ferrous hemoproteins", "with key ferrous hemoproteins serves", "key ferrous hemoproteins serves as", "ferrous hemoproteins serves as a", "hemoproteins serves as a posttranslational", "serves as a posttranslational modification", "as a posttranslational modification that", "a posttranslational modification that regulates", "posttranslational modification that regulates important", "modification that regulates important processes", "that regulates important processes as", "regulates important processes as diverse", "important processes as diverse as", "processes as diverse as aerobic", "as diverse as aerobic metabolism", "as aerobic metabolism oxidative", "aerobic metabolism oxidative stress", "oxidative stress and mitochondrial", "stress and mitochondrial bioenergetics.", "and mitochondrial bioenergetics. the most", "mitochondrial bioenergetics. the most important", "bioenergetics. the most important of", "the most important of these", "most important of these is", "important of these is the", "of these is the mitochondrial", "these is the mitochondrial cytochrome", "is the mitochondrial cytochrome c", "the mitochondrial cytochrome c oxidase", "cytochrome c oxidase cco", "c oxidase cco .", "oxidase cco . by", "cco . by locally blocking", ". by locally blocking mitochondrial", "by locally blocking mitochondrial respiration", "locally blocking mitochondrial respiration the", "blocking mitochondrial respiration the main", "mitochondrial respiration the main source", "respiration the main source of", "the main source of reactive", "main source of reactive oxygen", "source of reactive oxygen species", "reactive oxygen species ros", "species ros in", "ros in the cell", "in the cell is switched", "the cell is switched off.", "cell is switched off. additionally", "is switched off. additionally co", "switched off. additionally co enables", "off. additionally co enables efficient", "additionally co enables efficient reduction", "co enables efficient reduction of", "enables efficient reduction of methemoglobin", "reduction of methemoglobin methb", "methemoglobin methb by", "by h2o2 thus preventing", "h2o2 thus preventing the", "thus preventing the generation of", "preventing the generation of free", "the generation of free heme", "generation of free heme in", "of free heme in hemorrhagic", "free heme in hemorrhagic diseases", "heme in hemorrhagic diseases and", "in hemorrhagic diseases and malaria", "diseases and malaria origassa", "and malaria origassa and", "malaria origassa and c\u00e2mara", "origassa and c\u00e2mara 2013", "c\u00e2mara 2013 morse", "2013 morse et al", "morse et al 2009", "al 2009 ryter", "2009 ryter et al", "ryter et al 2006", "al 2006 cooper", "2006 cooper and brown", "cooper and brown 2008", "brown 2008 hinds", "2008 hinds and stec", "hinds and stec 2008", "and stec 2008 ." ] }, { "record_id": "GLY_000594_1_1923", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9707616", "r hsa", "hsa 9707616", "r hsa 9707616" ] }, { "record_id": "GLY_000594_1_1923", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "heme signaling", "extracellular hemoglobin", "a byproduct", "byproduct of", "of hemolysis", "can release", "release its", "its prosthetic", "prosthetic heme", "heme groups", "groups upon", "upon oxidation.", "oxidation. blood", "blood plasma", "plasma contains", "contains proteins", "proteins that", "that scavenge", "scavenge heme.", "heme. it", "it is", "is estimated", "estimated that", "that about", "about 2\u20138%", "2\u20138% of", "of the", "the heme", "heme released", "released in", "in plasma", "plasma becomes", "becomes \u2018bioavailable\u2019", "being internalized", "internalized by", "by bystander", "bystander cells.", "cells. if", "if the", "heme degradation", "degradation capacity", "capacity of", "of a", "a cell", "represented by", "by heme", "heme oxidase", "oxidase 1", "1 and", "and 2", "cannot be", "be ramped", "ramped up", "up sufficiently", "sufficiently then", "then heme", "signaling and", "and reactivity", "reactivity puts", "puts cells", "cells under", "under stress.", "stress. platelets", "platelets are", "are activated", "activated by", "and macrophages", "macrophages switch", "switch to", "to the", "the inflammatory", "inflammatory type", "donegan et", "et al", "gouveia et", "2019 .

              free", "heme accumulates", "accumulates in", "in the", "the blood", "blood stream", "stream in", "in great", "great amounts", "amounts under", "under pathological", "pathological conditions", "conditions like", "like viral", "viral infections", "infections and", "and malaria", "but also", "also ards", "ards amd", "amd copd.", "copd. the", "the locally", "locally affected", "affected cells'", "cells' primary", "primary reaction", "reaction is", "is to", "to upregulate", "upregulate heme", "expression. hmox1", "hmox1 induction", "induction in", "in these", "these cells", "cells not", "not only", "only removes", "removes heme", "heme from", "from circulation", "circulation but", "also triggers", "triggers a", "a functional", "functional switch", "switch toward", "toward the", "the anti", "anti inflammatory", "inflammatory phenotype", "vijayan et", "2018 .", ". however", "heme scavenging", "scavenging and", "and degradation", "degradation systems", "systems may", "may get", "get overwhelmed", "overwhelmed by", "by the", "the sheer", "sheer amount", "amount of", "of heme", "heme present.

              heme", "present.

              heme promotes", "promotes platelet", "platelet activation", "complement activation", "and thrombosis", "bourne et", "merle et", ". heme", "heme was", "was recognized", "recognized to", "to act", "act as", "as a", "a danger", "danger signal", "damage associated", "associated molecular", "molecular pattern", "or alarmin", "soares and", "and bozza", "and was", "was shown", "shown to", "to activate", "activate toll", "toll like", "like receptor", "receptor 4", "figueiredo et", "janciauskiene et", "2020 .", ". it", "it also", "also has", "has a", "a role", "role as", "as corepressor", "corepressor in", "the circadian", "circadian clock", "clock system", "ko and", "and takahashi", "2006 .", ". bach1", "bach1 is", "is regulated", "regulated by", "heme in", "in a", "thus placing", "placing heme", "heme as", "a signaling", "signaling molecule", "molecule in", "in gene", "gene expression", "expression in", "in higher", "higher eukaryotes.", "eukaryotes. the", "the regulation", "regulation of", "of bach1", "bach1 by", "heme may", "may be", "be important", "important for", "for the", "the stress", "stress response", "response in", "in general", "suzuki et", "2004 .

              extracellular", ".

              extracellular hemoglobin", "groups uponoxidation.", "uponoxidation. due", "due to", "the reactive", "reactive nature", "nature of", "of free", "free heme", "cells. failure", "failure of", "of nearby", "nearby cells", "cells to", "to sufficientlymetabolize", "sufficientlymetabolize free", "heme can", "can incite", "incite platelet", "macrophage differentiation", "and oxidative", "oxidative stress", "2019 .", "hemoglobin a", "a byproduct of", "byproduct of hemolysis", "hemolysis can", "can release its", "release its prosthetic", "its prosthetic heme", "prosthetic heme groups", "heme groups upon", "groups upon oxidation.", "upon oxidation. blood", "oxidation. blood plasma", "blood plasma contains", "plasma contains proteins", "contains proteins that", "proteins that scavenge", "that scavenge heme.", "scavenge heme. it", "heme. it is", "it is estimated", "is estimated that", "estimated that about", "that about 2\u20138%", "about 2\u20138% of", "2\u20138% of the", "of the heme", "the heme released", "heme released in", "released in plasma", "in plasma becomes", "plasma becomes \u2018bioavailable\u2019", "\u2018bioavailable\u2019 being", "being internalized by", "internalized by bystander", "by bystander cells.", "bystander cells. if", "cells. if the", "if the heme", "the heme degradation", "heme degradation capacity", "degradation capacity of", "capacity of a", "of a cell", "cell represented", "represented by heme", "by heme oxidase", "heme oxidase 1", "oxidase 1 and", "1 and 2", "2 cannot", "cannot be ramped", "be ramped up", "ramped up sufficiently", "up sufficiently then", "sufficiently then heme", "then heme signaling", "heme signaling and", "signaling and reactivity", "and reactivity puts", "reactivity puts cells", "puts cells under", "cells under stress.", "under stress. platelets", "stress. platelets are", "platelets are activated", "are activated by", "activated by heme", "heme and", "and macrophages switch", "macrophages switch to", "switch to the", "to the inflammatory", "the inflammatory type", "type donegan", "donegan et al", "al 2019", "2019 gouveia", "gouveia et al", ".

              free labile", "labile heme", "heme accumulates in", "accumulates in the", "in the blood", "the blood stream", "blood stream in", "stream in great", "in great amounts", "great amounts under", "amounts under pathological", "under pathological conditions", "pathological conditions like", "conditions like viral", "like viral infections", "viral infections and", "infections and malaria", "malaria but", "but also ards", "also ards amd", "ards amd copd.", "amd copd. the", "copd. the locally", "the locally affected", "locally affected cells'", "affected cells' primary", "cells' primary reaction", "primary reaction is", "reaction is to", "is to upregulate", "to upregulate heme", "upregulate heme oxidase", "1 hmox1", "hmox1 expression.", "expression. hmox1 induction", "hmox1 induction in", "induction in these", "in these cells", "these cells not", "cells not only", "not only removes", "only removes heme", "removes heme from", "heme from circulation", "from circulation but", "circulation but also", "but also triggers", "also triggers a", "triggers a functional", "a functional switch", "functional switch toward", "switch toward the", "toward the anti", "the anti inflammatory", "anti inflammatory phenotype", "phenotype vijayan", "vijayan et al", "al 2018", "2018 . however", "however heme", "heme scavenging and", "scavenging and degradation", "and degradation systems", "degradation systems may", "systems may get", "may get overwhelmed", "get overwhelmed by", "overwhelmed by the", "by the sheer", "the sheer amount", "sheer amount of", "amount of heme", "of heme present.

              heme", "heme present.

              heme promotes", "present.

              heme promotes platelet", "promotes platelet activation", "activation complement", "activation vasculitis", "vasculitis and", "thrombosis bourne", "bourne et al", "al 2020", "2020 merle", "merle et al", "2018 . heme", ". heme was", "heme was recognized", "was recognized to", "recognized to act", "to act as", "act as a", "as a danger", "a danger signal", "signal damage", "damage associated molecular", "associated molecular pattern", "pattern damp", "alarmin soares", "soares and bozza", "bozza 2016", "2016 and", "and was shown", "was shown to", "shown to activate", "to activate toll", "activate toll like", "toll like receptor", "like receptor 4", "4 tlr4", "tlr4 signaling", "signaling figueiredo", "figueiredo et al", "al 2007", "2007 janciauskiene", "janciauskiene et al", "2020 . it", ". it also", "it also has", "also has a", "has a role", "a role as", "role as corepressor", "as corepressor in", "corepressor in the", "in the circadian", "the circadian clock", "circadian clock system", "system ko", "ko and takahashi", "takahashi 2006", "2006 . bach1", ". bach1 is", "bach1 is regulated", "is regulated by", "regulated by heme", "by heme in", "heme in a", "in a cell", "cell thus", "thus placing heme", "placing heme as", "heme as a", "as a signaling", "a signaling molecule", "signaling molecule in", "molecule in gene", "in gene expression", "gene expression in", "expression in higher", "in higher eukaryotes.", "higher eukaryotes. the", "eukaryotes. the regulation", "the regulation of", "regulation of bach1", "of bach1 by", "bach1 by heme", "by heme may", "heme may be", "may be important", "be important for", "important for the", "for the stress", "the stress response", "stress response in", "response in general", "general suzuki", "suzuki et al", "al 2004", "2004 .

              extracellular hemoglobin", "heme groups uponoxidation.", "groups uponoxidation. due", "uponoxidation. due to", "due to the", "to the reactive", "the reactive nature", "reactive nature of", "nature of free", "of free heme", "heme the", "the blood plasma", "bystander cells. failure", "cells. failure of", "failure of nearby", "of nearby cells", "nearby cells to", "cells to sufficientlymetabolize", "to sufficientlymetabolize free", "sufficientlymetabolize free heme", "free heme can", "heme can incite", "can incite platelet", "incite platelet activation", "activation macrophage", "differentiation and", "and oxidative stress", "stress donegan", "extracellular hemoglobin a", "hemoglobin a byproduct", "a byproduct of hemolysis", "of hemolysis can", "hemolysis can release", "can release its prosthetic", "release its prosthetic heme", "its prosthetic heme groups", "prosthetic heme groups upon", "heme groups upon oxidation.", "groups upon oxidation. blood", "upon oxidation. blood plasma", "oxidation. blood plasma contains", "blood plasma contains proteins", "plasma contains proteins that", "contains proteins that scavenge", "proteins that scavenge heme.", "that scavenge heme. it", "scavenge heme. it is", "heme. it is estimated", "it is estimated that", "is estimated that about", "estimated that about 2\u20138%", "that about 2\u20138% of", "about 2\u20138% of the", "2\u20138% of the heme", "of the heme released", "the heme released in", "heme released in plasma", "released in plasma becomes", "in plasma becomes \u2018bioavailable\u2019", "becomes \u2018bioavailable\u2019 being", "\u2018bioavailable\u2019 being internalized", "being internalized by bystander", "internalized by bystander cells.", "by bystander cells. if", "bystander cells. if the", "cells. if the heme", "if the heme degradation", "the heme degradation capacity", "heme degradation capacity of", "degradation capacity of a", "capacity of a cell", "a cell represented", "cell represented by", "represented by heme oxidase", "by heme oxidase 1", "heme oxidase 1 and", "oxidase 1 and 2", "and 2 cannot", "2 cannot be", "cannot be ramped up", "be ramped up sufficiently", "ramped up sufficiently then", "up sufficiently then heme", "sufficiently then heme signaling", "then heme signaling and", "heme signaling and reactivity", "signaling and reactivity puts", "and reactivity puts cells", "reactivity puts cells under", "puts cells under stress.", "cells under stress. platelets", "under stress. platelets are", "stress. platelets are activated", "platelets are activated by", "are activated by heme", "by heme and", "heme and macrophages", "and macrophages switch to", "macrophages switch to the", "switch to the inflammatory", "to the inflammatory type", "inflammatory type donegan", "type donegan et", "et al 2019", "2019 gouveia et", "al 2019 .

              free", "2019 .

              free labile", "labile heme accumulates", "heme accumulates in the", "accumulates in the blood", "in the blood stream", "the blood stream in", "blood stream in great", "stream in great amounts", "in great amounts under", "great amounts under pathological", "amounts under pathological conditions", "under pathological conditions like", "pathological conditions like viral", "conditions like viral infections", "like viral infections and", "viral infections and malaria", "and malaria but", "malaria but also", "but also ards amd", "also ards amd copd.", "ards amd copd. the", "amd copd. the locally", "copd. the locally affected", "the locally affected cells'", "locally affected cells' primary", "affected cells' primary reaction", "cells' primary reaction is", "primary reaction is to", "reaction is to upregulate", "is to upregulate heme", "to upregulate heme oxidase", "upregulate heme oxidase 1", "oxidase 1 hmox1", "hmox1 expression. hmox1", "expression. hmox1 induction in", "hmox1 induction in these", "induction in these cells", "in these cells not", "these cells not only", "cells not only removes", "not only removes heme", "only removes heme from", "removes heme from circulation", "heme from circulation but", "from circulation but also", "circulation but also triggers", "but also triggers a", "also triggers a functional", "triggers a functional switch", "a functional switch toward", "functional switch toward the", "switch toward the anti", "toward the anti inflammatory", "the anti inflammatory phenotype", "inflammatory phenotype vijayan", "phenotype vijayan et", "et al 2018", "al 2018 .", ". however heme", "however heme scavenging", "heme scavenging and degradation", "scavenging and degradation systems", "and degradation systems may", "degradation systems may get", "systems may get overwhelmed", "may get overwhelmed by", "get overwhelmed by the", "overwhelmed by the sheer", "by the sheer amount", "the sheer amount of", "sheer amount of heme", "amount of heme present.

              heme", "of heme present.

              heme promotes", "heme present.

              heme promotes platelet", "present.

              heme promotes platelet activation", "platelet activation complement", "activation complement activation", "complement activation vasculitis", "vasculitis and thrombosis", "and thrombosis bourne", "thrombosis bourne et", "et al 2020", "2020 merle et", "2018 . heme was", ". heme was recognized", "heme was recognized to", "was recognized to act", "recognized to act as", "to act as a", "act as a danger", "as a danger signal", "danger signal damage", "signal damage associated", "damage associated molecular pattern", "molecular pattern damp", "damp or", "or alarmin soares", "alarmin soares and", "and bozza 2016", "2016 and was", "and was shown to", "was shown to activate", "shown to activate toll", "to activate toll like", "activate toll like receptor", "toll like receptor 4", "receptor 4 tlr4", "signaling figueiredo et", "et al 2007", "2007 janciauskiene et", "al 2020 .", "2020 . it also", ". it also has", "it also has a", "also has a role", "has a role as", "a role as corepressor", "role as corepressor in", "as corepressor in the", "corepressor in the circadian", "in the circadian clock", "the circadian clock system", "clock system ko", "system ko and", "and takahashi 2006", "takahashi 2006 .", "2006 . bach1 is", ". bach1 is regulated", "bach1 is regulated by", "is regulated by heme", "regulated by heme in", "by heme in a", "heme in a cell", "a cell thus", "cell thus placing", "thus placing heme as", "placing heme as a", "heme as a signaling", "as a signaling molecule", "a signaling molecule in", "signaling molecule in gene", "molecule in gene expression", "in gene expression in", "gene expression in higher", "expression in higher eukaryotes.", "in higher eukaryotes. the", "higher eukaryotes. the regulation", "eukaryotes. the regulation of", "the regulation of bach1", "regulation of bach1 by", "of bach1 by heme", "bach1 by heme may", "by heme may be", "heme may be important", "may be important for", "be important for the", "important for the stress", "for the stress response", "the stress response in", "stress response in general", "in general suzuki", "general suzuki et", "et al 2004", "al 2004 .

              extracellular", ".

              extracellular hemoglobin a", "prosthetic heme groups uponoxidation.", "heme groups uponoxidation. due", "groups uponoxidation. due to", "uponoxidation. due to the", "due to the reactive", "to the reactive nature", "the reactive nature of", "reactive nature of free", "nature of free heme", "free heme the", "heme the blood", "the blood plasma contains", "by bystander cells. failure", "bystander cells. failure of", "cells. failure of nearby", "failure of nearby cells", "of nearby cells to", "nearby cells to sufficientlymetabolize", "cells to sufficientlymetabolize free", "to sufficientlymetabolize free heme", "sufficientlymetabolize free heme can", "free heme can incite", "heme can incite platelet", "can incite platelet activation", "platelet activation macrophage", "activation macrophage differentiation", "macrophage differentiation and", "differentiation and oxidative", "oxidative stress donegan", "stress donegan et", "al 2019 .", "extracellular hemoglobin a byproduct", "hemoglobin a byproduct of", "byproduct of hemolysis can", "of hemolysis can release", "hemolysis can release its", "can release its prosthetic heme", "release its prosthetic heme groups", "its prosthetic heme groups upon", "prosthetic heme groups upon oxidation.", "heme groups upon oxidation. blood", "groups upon oxidation. blood plasma", "upon oxidation. blood plasma contains", "oxidation. blood plasma contains proteins", "blood plasma contains proteins that", "plasma contains proteins that scavenge", "contains proteins that scavenge heme.", "proteins that scavenge heme. it", "that scavenge heme. it is", "scavenge heme. it is estimated", "heme. it is estimated that", "it is estimated that about", "is estimated that about 2\u20138%", "estimated that about 2\u20138% of", "that about 2\u20138% of the", "about 2\u20138% of the heme", "2\u20138% of the heme released", "of the heme released in", "the heme released in plasma", "heme released in plasma becomes", "released in plasma becomes \u2018bioavailable\u2019", "plasma becomes \u2018bioavailable\u2019 being", "becomes \u2018bioavailable\u2019 being internalized", "\u2018bioavailable\u2019 being internalized by", "being internalized by bystander cells.", "internalized by bystander cells. if", "by bystander cells. if the", "bystander cells. if the heme", "cells. if the heme degradation", "if the heme degradation capacity", "the heme degradation capacity of", "heme degradation capacity of a", "degradation capacity of a cell", "of a cell represented", "a cell represented by", "cell represented by heme", "represented by heme oxidase 1", "by heme oxidase 1 and", "heme oxidase 1 and 2", "1 and 2 cannot", "and 2 cannot be", "2 cannot be ramped", "cannot be ramped up sufficiently", "be ramped up sufficiently then", "ramped up sufficiently then heme", "up sufficiently then heme signaling", "sufficiently then heme signaling and", "then heme signaling and reactivity", "heme signaling and reactivity puts", "signaling and reactivity puts cells", "and reactivity puts cells under", "reactivity puts cells under stress.", "puts cells under stress. platelets", "cells under stress. platelets are", "under stress. platelets are activated", "stress. platelets are activated by", "platelets are activated by heme", "activated by heme and", "by heme and macrophages", "heme and macrophages switch", "and macrophages switch to the", "macrophages switch to the inflammatory", "switch to the inflammatory type", "the inflammatory type donegan", "inflammatory type donegan et", "type donegan et al", "donegan et al 2019", "al 2019 gouveia", "2019 gouveia et al", "gouveia et al 2019", "et al 2019 .

              free", ".

              free labile heme", "labile heme accumulates in", "heme accumulates in the blood", "accumulates in the blood stream", "in the blood stream in", "the blood stream in great", "blood stream in great amounts", "stream in great amounts under", "in great amounts under pathological", "great amounts under pathological conditions", "amounts under pathological conditions like", "under pathological conditions like viral", "pathological conditions like viral infections", "conditions like viral infections and", "like viral infections and malaria", "infections and malaria but", "and malaria but also", "malaria but also ards", "but also ards amd copd.", "also ards amd copd. the", "ards amd copd. the locally", "amd copd. the locally affected", "copd. the locally affected cells'", "the locally affected cells' primary", "locally affected cells' primary reaction", "affected cells' primary reaction is", "cells' primary reaction is to", "primary reaction is to upregulate", "reaction is to upregulate heme", "is to upregulate heme oxidase", "to upregulate heme oxidase 1", "heme oxidase 1 hmox1", "1 hmox1 expression.", "hmox1 expression. hmox1 induction", "expression. hmox1 induction in these", "hmox1 induction in these cells", "induction in these cells not", "in these cells not only", "these cells not only removes", "cells not only removes heme", "not only removes heme from", "only removes heme from circulation", "removes heme from circulation but", "heme from circulation but also", "from circulation but also triggers", "circulation but also triggers a", "but also triggers a functional", "also triggers a functional switch", "triggers a functional switch toward", "a functional switch toward the", "functional switch toward the anti", "switch toward the anti inflammatory", "toward the anti inflammatory phenotype", "anti inflammatory phenotype vijayan", "inflammatory phenotype vijayan et", "phenotype vijayan et al", "vijayan et al 2018", "et al 2018 .", "al 2018 . however", "2018 . however heme", ". however heme scavenging", "however heme scavenging and", "heme scavenging and degradation systems", "scavenging and degradation systems may", "and degradation systems may get", "degradation systems may get overwhelmed", "systems may get overwhelmed by", "may get overwhelmed by the", "get overwhelmed by the sheer", "overwhelmed by the sheer amount", "by the sheer amount of", "the sheer amount of heme", "sheer amount of heme present.

              heme", "amount of heme present.

              heme promotes", "of heme present.

              heme promotes platelet", "heme present.

              heme promotes platelet activation", "promotes platelet activation complement", "platelet activation complement activation", "activation vasculitis and", "and thrombosis bourne et", "thrombosis bourne et al", "bourne et al 2020", "al 2020 merle", "2020 merle et al", "merle et al 2018", "al 2018 . heme", "2018 . heme was recognized", ". heme was recognized to", "heme was recognized to act", "was recognized to act as", "recognized to act as a", "to act as a danger", "act as a danger signal", "a danger signal damage", "danger signal damage associated", "signal damage associated molecular", "associated molecular pattern damp", "damp or alarmin", "or alarmin soares and", "alarmin soares and bozza", "soares and bozza 2016", "bozza 2016 and", "2016 and was shown", "and was shown to activate", "was shown to activate toll", "shown to activate toll like", "to activate toll like receptor", "activate toll like receptor 4", "like receptor 4 tlr4", "4 tlr4 signaling", "tlr4 signaling figueiredo", "signaling figueiredo et al", "figueiredo et al 2007", "al 2007 janciauskiene", "2007 janciauskiene et al", "janciauskiene et al 2020", "et al 2020 .", "al 2020 . it", "2020 . it also has", ". it also has a", "it also has a role", "also has a role as", "has a role as corepressor", "a role as corepressor in", "role as corepressor in the", "as corepressor in the circadian", "corepressor in the circadian clock", "in the circadian clock system", "circadian clock system ko", "clock system ko and", "system ko and takahashi", "ko and takahashi 2006", "and takahashi 2006 .", "takahashi 2006 . bach1", "2006 . bach1 is regulated", ". bach1 is regulated by", "bach1 is regulated by heme", "is regulated by heme in", "regulated by heme in a", "by heme in a cell", "in a cell thus", "a cell thus placing", "cell thus placing heme", "thus placing heme as a", "placing heme as a signaling", "heme as a signaling molecule", "as a signaling molecule in", "a signaling molecule in gene", "signaling molecule in gene expression", "molecule in gene expression in", "in gene expression in higher", "gene expression in higher eukaryotes.", "expression in higher eukaryotes. the", "in higher eukaryotes. the regulation", "higher eukaryotes. the regulation of", "eukaryotes. the regulation of bach1", "the regulation of bach1 by", "regulation of bach1 by heme", "of bach1 by heme may", "bach1 by heme may be", "by heme may be important", "heme may be important for", "may be important for the", "be important for the stress", "important for the stress response", "for the stress response in", "the stress response in general", "response in general suzuki", "in general suzuki et", "general suzuki et al", "suzuki et al 2004", "et al 2004 .

              extracellular", "al 2004 .

              extracellular hemoglobin", "2004 .

              extracellular hemoglobin a", ".

              extracellular hemoglobin a byproduct", "its prosthetic heme groups uponoxidation.", "prosthetic heme groups uponoxidation. due", "heme groups uponoxidation. due to", "groups uponoxidation. due to the", "uponoxidation. due to the reactive", "due to the reactive nature", "to the reactive nature of", "the reactive nature of free", "reactive nature of free heme", "of free heme the", "free heme the blood", "heme the blood plasma", "the blood plasma contains proteins", "internalized by bystander cells. failure", "by bystander cells. failure of", "bystander cells. failure of nearby", "cells. failure of nearby cells", "failure of nearby cells to", "of nearby cells to sufficientlymetabolize", "nearby cells to sufficientlymetabolize free", "cells to sufficientlymetabolize free heme", "to sufficientlymetabolize free heme can", "sufficientlymetabolize free heme can incite", "free heme can incite platelet", "heme can incite platelet activation", "incite platelet activation macrophage", "platelet activation macrophage differentiation", "macrophage differentiation and oxidative", "differentiation and oxidative stress", "and oxidative stress donegan", "oxidative stress donegan et", "stress donegan et al", "et al 2019 ." ] }, { "record_id": "GLY_000594_1_1924", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9725370", "r hsa", "hsa 9725370", "r hsa 9725370" ] }, { "record_id": "GLY_000594_1_1924", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by alk", "alk fusions", "fusions and", "and activated", "activated point", "point mutants", "signaling by alk", "by alk fusions", "alk fusions and", "fusions and activated", "and activated point", "activated point mutants", "signaling by alk fusions", "by alk fusions and", "alk fusions and activated", "fusions and activated point", "and activated point mutants", "signaling by alk fusions and", "by alk fusions 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"GLY_000594_1_1925", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9707587", "r hsa", "hsa 9707587", "r hsa 9707587" ] }, { "record_id": "GLY_000594_1_1925", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of hmox1", "hmox1 expression", "expression and", "and activity", "regulation of hmox1", "of hmox1 expression", "hmox1 expression and", "expression and activity", "regulation of hmox1 expression", "of hmox1 expression and", "hmox1 expression and activity", "regulation of hmox1 expression and", "of hmox1 expression and activity", "heme oxygenase", "oxygenase 1", "is regulated", "regulated at", "at the", "the level", "level of", "of gene", "gene transcription", "mrna translation", "localization and", "and degradation.", "degradation. its", "its gene", "gene is", "is often", "often activated", "activated under", "under a", "a wide", "wide range", "range of", "of stressful", 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              ares", ".

              ares on", "on the", "the hmox1", "hmox1 gene", "gene are", "are ultimately", "ultimately controlled", "controlled by", "by the", "the enhancing", "enhancing nfe2l2:mafk", "nfe2l2:mafk dimer", "dimer and", "and the", "the repressing", "repressing bach1:mafk", "bach1:mafk dimer", "both of", "of which", "which are", "are influenced", "influenced by", "by a", "a multitude", "multitude of", "of processes.", "processes. less", "less specific", "specific enhancement", "enhancement occurs", "occurs via", "via ap", "ap 1", "funes et", "2020 .

              hmox1", ".

              hmox1 activity", "activity depends", "depends on", "on dimerization", "dimerization in", "the er", "er membrane.", "membrane. its", "its membrane", "membrane localization", "localization is", "is abandoned", "abandoned by", "by cleavage", "cleavage of", "the membrane", "membrane domain", "domain by", "by hm13.", "hm13. the", "the resulting", "resulting soluble", "soluble enzyme", "enzyme is", "is found", "found in", "the cytosol", "the nucleus", "schaefer et", "2017 .", "heme oxygenase 1", "1 hmox1", "is regulated at", "regulated at the", "at the level", "the level of", "level of gene", "of gene transcription", "transcription mrna", "translation localization", "localization and degradation.", "and degradation. its", "degradation. its gene", "its gene is", "gene is often", "is often activated", "often activated under", "activated under a", "under a wide", "a wide range", "wide range of", "range of stressful", "of stressful conditions.", "stressful conditions. the", "conditions. the transcriptional", "the transcriptional control", "transcriptional control of", "control of hmox1", "of hmox1 is", "hmox1 is determined", "is determined by", "determined by inducible", "by inducible regulatory", "inducible regulatory elements", "regulatory elements localized", "elements localized in", "localized in the", "in the 5\u2032", "the 5\u2032 region", "5\u2032 region of", "region of the", "of the promoter", "promoter so", "so called antioxidant", "called antioxidant response", "antioxidant response elements", "elements are", "are raghunath", "raghunath et al", "al 2018", "2018 .

              ares on", ".

              ares on the", "on the hmox1", "the hmox1 gene", "hmox1 gene are", "gene are ultimately", "are ultimately controlled", "ultimately controlled by", "controlled by the", "by the enhancing", "the enhancing nfe2l2:mafk", "enhancing nfe2l2:mafk dimer", "nfe2l2:mafk dimer and", "dimer and the", "and the repressing", "the repressing bach1:mafk", "repressing bach1:mafk dimer", "dimer both", "both of which", "of which are", "which are influenced", "are influenced by", "influenced by a", "by a multitude", "a multitude of", "multitude of processes.", "of processes. less", "processes. less specific", "less specific enhancement", "specific enhancement occurs", "enhancement occurs via", "occurs via ap", "via ap 1", "1 fos:jun", "fos:jun dimers", "dimers funes", "funes et al", "al 2020", "2020 .

              hmox1 activity", ".

              hmox1 activity depends", "activity depends on", "depends on dimerization", "on dimerization in", "dimerization in the", "in the er", "the er membrane.", "er membrane. its", "membrane. its membrane", "its membrane localization", "membrane localization is", "localization is abandoned", "is abandoned by", "abandoned by cleavage", "by cleavage of", "cleavage of the", "of the membrane", "the membrane domain", "membrane domain by", "domain by hm13.", "by hm13. the", "hm13. the resulting", "the resulting soluble", "resulting soluble enzyme", "soluble enzyme is", "enzyme is found", "is found in", "found in the", "in the cytosol", "cytosol mitochondria", "mitochondria and", "and the nucleus", "nucleus schaefer", "schaefer et al", "al 2017", "oxygenase 1 hmox1", "hmox1 is regulated", "is regulated at the", "regulated at the level", "at the level of", "the level of gene", "level of gene transcription", "gene transcription mrna", "transcription mrna translation", "mrna translation localization", "translation localization and", "localization and degradation. its", "and degradation. its gene", "degradation. its gene is", "its gene is often", "gene is often activated", "is often activated under", "often activated under a", "activated under a wide", "under a wide range", "a wide range of", "wide range of stressful", "range of stressful conditions.", "of stressful conditions. the", "stressful conditions. the transcriptional", "conditions. the transcriptional control", "the transcriptional control of", "transcriptional control of hmox1", "control of hmox1 is", "of hmox1 is determined", "hmox1 is determined by", "is determined by inducible", "determined by inducible regulatory", "by inducible regulatory elements", "inducible regulatory elements localized", "regulatory elements localized in", "elements localized in the", "localized in the 5\u2032", "in the 5\u2032 region", "the 5\u2032 region of", "5\u2032 region of the", "region of the promoter", "the promoter so", "promoter so called", "so called antioxidant response", "called antioxidant response elements", "response elements are", "are raghunath et", "et al 2018", "al 2018 .

              ares", "2018 .

              ares on the", ".

              ares on the hmox1", "on the hmox1 gene", "the hmox1 gene are", "hmox1 gene are ultimately", "gene are ultimately controlled", "are ultimately controlled by", "ultimately controlled by the", "controlled by the enhancing", "by the enhancing nfe2l2:mafk", "the enhancing nfe2l2:mafk dimer", "enhancing nfe2l2:mafk dimer and", "nfe2l2:mafk dimer and the", "dimer and the repressing", "and the repressing bach1:mafk", "the repressing bach1:mafk dimer", "bach1:mafk dimer both", "dimer both of", "both of which are", "of which are influenced", "which are influenced by", "are influenced by a", "influenced by a multitude", "by a multitude of", "a multitude of processes.", "multitude of processes. less", "of processes. less specific", "processes. less specific enhancement", "less specific enhancement occurs", "specific enhancement occurs via", "enhancement occurs via ap", "occurs via ap 1", "ap 1 fos:jun", "dimers funes et", "et al 2020", "al 2020 .

              hmox1", "2020 .

              hmox1 activity depends", ".

              hmox1 activity depends on", "activity depends on dimerization", "depends on dimerization in", "on dimerization in the", "dimerization in the er", "in the er membrane.", "the er membrane. its", "er membrane. its membrane", "membrane. its membrane localization", "its membrane localization is", "membrane localization is abandoned", "localization is abandoned by", "is abandoned by cleavage", "abandoned by cleavage of", "by cleavage of the", "cleavage of the membrane", "of the membrane domain", "the membrane domain by", "membrane domain by hm13.", "domain by hm13. the", "by hm13. the resulting", "hm13. the resulting soluble", "the resulting soluble enzyme", "resulting soluble enzyme is", "soluble enzyme is found", "enzyme is found in", "is found in the", "found in the cytosol", "the cytosol mitochondria", "mitochondria and the", "the nucleus schaefer", "nucleus schaefer et", "et al 2017", "al 2017 .", "heme oxygenase 1 hmox1", "1 hmox1 is", "hmox1 is regulated at", "is regulated at the level", "regulated at the level of", "at the level of gene", "the level of gene transcription", "of gene transcription mrna", "gene transcription mrna translation", "mrna translation localization and", "translation localization and degradation.", "localization and degradation. its gene", "and degradation. its gene is", "degradation. its gene is often", "its gene is often activated", "gene is often activated under", "is often activated under a", "often activated under a wide", "activated under a wide range", "under a wide range of", "a wide range of stressful", "wide range of stressful conditions.", "range of stressful conditions. the", "of stressful conditions. the transcriptional", "stressful conditions. the transcriptional control", "conditions. the transcriptional control of", "the transcriptional control of hmox1", "transcriptional control of hmox1 is", "control of hmox1 is determined", "of hmox1 is determined by", "hmox1 is determined by inducible", "is determined by inducible regulatory", "determined by inducible regulatory elements", "by inducible regulatory elements localized", "inducible regulatory elements localized in", "regulatory elements localized in the", "elements localized in the 5\u2032", "localized in the 5\u2032 region", "in the 5\u2032 region of", "the 5\u2032 region of the", "5\u2032 region of the promoter", "of the promoter so", "the promoter so called", "promoter so called antioxidant", "so called antioxidant response elements", "antioxidant response elements are", "elements are raghunath", "are raghunath et al", "raghunath et al 2018", "et al 2018 .

              ares", "al 2018 .

              ares on", "2018 .

              ares on the hmox1", ".

              ares on the hmox1 gene", "on the hmox1 gene are", "the hmox1 gene are ultimately", "hmox1 gene are ultimately controlled", "gene are ultimately controlled by", "are ultimately controlled by the", "ultimately controlled by the enhancing", "controlled by the enhancing nfe2l2:mafk", "by the enhancing nfe2l2:mafk dimer", "the enhancing nfe2l2:mafk dimer and", "enhancing nfe2l2:mafk dimer and the", "nfe2l2:mafk dimer and the repressing", "dimer and the repressing bach1:mafk", "and the repressing bach1:mafk dimer", "repressing bach1:mafk dimer both", "bach1:mafk dimer both of", "dimer both of which", "both of which are influenced", "of which are influenced by", "which are influenced by a", "are influenced by a multitude", "influenced by a multitude of", "by a multitude of processes.", "a multitude of processes. less", "multitude of processes. less specific", "of processes. less specific enhancement", "processes. less specific enhancement occurs", "less specific enhancement occurs via", "specific enhancement occurs via ap", "enhancement occurs via ap 1", "via ap 1 fos:jun", "1 fos:jun dimers", "fos:jun dimers funes", "dimers funes et al", "funes et al 2020", "et al 2020 .

              hmox1", "al 2020 .

              hmox1 activity", "2020 .

              hmox1 activity depends on", ".

              hmox1 activity depends on dimerization", "activity depends on dimerization in", "depends on dimerization in the", "on dimerization in the er", "dimerization in the er membrane.", "in the er membrane. its", "the er membrane. its membrane", "er membrane. its membrane localization", "membrane. its membrane localization is", "its membrane localization is abandoned", "membrane localization is abandoned by", "localization is abandoned by cleavage", "is abandoned by cleavage of", "abandoned by cleavage of the", "by cleavage of the membrane", "cleavage of the membrane domain", "of the membrane domain by", "the membrane domain by hm13.", "membrane domain by hm13. the", "domain by hm13. the resulting", "by hm13. the resulting soluble", "hm13. the resulting soluble enzyme", "the resulting soluble enzyme is", "resulting soluble enzyme is found", "soluble enzyme is found in", "enzyme is found in the", "is found in the cytosol", "in the cytosol mitochondria", "cytosol mitochondria and", "mitochondria and the nucleus", "and the nucleus schaefer", "the nucleus schaefer et", "nucleus schaefer et al", "schaefer et al 2017", "et al 2017 ." ] }, { "record_id": "GLY_000594_1_1926", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9708530", "r hsa", "hsa 9708530", "r hsa 9708530" ] }, { "record_id": "GLY_000594_1_1926", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of bach1", "bach1 activity", "regulation of bach1", "of bach1 activity", "regulation of bach1 activity", "the transcription", "transcription factor", "factor btb", "btb and", "and cnc", "cnc homology", "homology 1", "is widely", "widely expressed", "expressed in", "in most", "most mammalian", "mammalian tissues", "tissues and", "and functions", "functions primarily", "primarily as", "as a", "a transcriptional", "transcriptional suppressor", "suppressor by", "by heterodimerizing", "heterodimerizing 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"c\u2011terminal domain", "domain reported", "reported to", "to inhibit", "inhibit cell", "death through", "through intramolecular", "intramolecular domain", "domain association", "liu z", "z et", "kuang s", "s et", "2017 .", ". proteolytic", "proteolytic cleavage", "cleavage in", "in the", "the linker", "linker connecting", "connecting the", "the n\u2011", "n\u2011 and", "and c\u2011terminal", "c\u2011terminal domains", "domains of", "of gasdermins", "gasdermins releases", "releases the", "the c\u2011terminus", "allowing the", "gasdermin n\u2011terminus", "n\u2011terminus to", "to translocate", "translocate to", "to the", "and oligomerize", "oligomerize to", "to form", "form pores", "al. 2015", "sborgi l", "feng s", "yang j", ". although", "although pjvk", "is included", "included to", "it is", "not known", "known whether", "whether pjvk", "pjvk is", "is cleaved", "cleaved and", "and whether", "whether the", "the full", "full length", "length or", "or the", "the n", "terminal portion", "portion of", "of pjvk", "is responsible", "responsible for", "for forming", "forming membrane", "membrane pores.", "pores. the", "the n\u2011terminal", "n\u2011terminal fragments", "fragments of", "of gsdms", "gsdms strongly", "strongly bind", "bind to", "to phosphatidylinositol", "phosphatidylinositol phosphates", "phosphates and", "and weakly", "weakly to", "to phosphatidylserine", "found on", "on the", "the inner", "inner leaflet", "leaflet of", "the plasma", "plasma membrane", ". gasdermins", "gasdermins are", "are also", "also able", "able to", "to target", "target cardiolipin", "which is", "is often", "often found", "found in", "in mitochondrial", "mitochondrial membranes", "membranes and", "and membranes", "membranes of", "of bacteria", "rogers c", "c et", "the size", "size of", "the gsdmd", "gsdmd pore", "pore is", "is estimated", "estimated to", "to be", "be 10\u201320", "10\u201320 nm", "2016 .", "the pore\u2011forming", "pore\u2011forming activity", "activity of", "gsdms in", "membrane facilitates", "facilitates the", "the release", "of inflammatory", "inflammatory molecules", "molecules such", "as interleukin", "il \u20111\u03b2", "\u20111\u03b2 and", "and il\u201118", "mainly in", "in gsdmd", "gsdmd mediated", "mediated pyroptosis", "and eventually", "eventually leads", "leads to", "to cytolysis", "cytolysis in", "in mammalian", "mammalian cells", "releasing additional", "additional proinflammatory", "proinflammatory cellular", "cellular contents", "contents including", "including danger", "danger signals", "signals such", "as high", "high mobility", "mobility group", "group box\u20111", "he w", "w et", "evavold cl", "cl et", "semino c", "volchuk a", "a et", "can occur", "occur in", "in immune", "immune cells", "cells such", "as macrophages", "monocytes and", "and dendritic", "dendritic cells", "cells and", "and non\u2011immune", "non\u2011immune cell", "cell types", "types such", "as intestinal", "intestinal epithelial", "epithelial cells", "trophoblasts and", "and hepatocytes", "taabazuing cy", "cy et", "li h", "h et", "jia c", ". gsdme", "gsdme can", "be cleaved", "cleaved by", "by caspase\u20113", "to induce", "induce pyroptosis", "pyroptosis downstream", "downstream of", "the \u201capoptotic\u201d", "\u201capoptotic\u201d machinery", "wang y", "y et", "whereas gsdmd", "gsdmd is", "by inflammatory", "inflammatory casp1", "casp4 and", "and casp5", "casp5 in", "in humans", "and casp1", "casp11 in", "in mice", "mice to", "pyroptosis associated", "associated with", "with inflammasome", "inflammasome activation", "kayagaki n", "n et", "2015 .", ". casp3", "casp3 cleavage", "cleavage of", "of gsdmd", "gsdmd results", "results in", "in its", "its inactivation", "taabazuing et", ". in", "in mouse", "mouse macrophages", "casp8 can", "also cleave", "cleave gsdmd", "gsdmd and", "and cause", "cause pyroptosis", "pyroptosis when", "when tak1", "tak1 is", "is inhibited", "malireddi r", "r et", "orning p", "sarhan j", "and tak1", "tak1 inhibition", "inhibition also", "also leads", "to gsdme", "gsdme cleavage", ". furthermore", "activated casp8", "can drive", "drive inflammasome", "inflammasome independent", "independent cleavage", "of both", "both pro", "pro il", "il 1\u03b2", "1\u03b2 and", "and gsdmd", "gsdmd downstream", "the extrinsic", "extrinsic cell", "death receptor", "receptor signaling", "signaling pathway", "pathway switching", "switching apoptotic", "apoptotic signaling", "signaling to", "to gsdmd", "gsdmd dependent", "dependent pyroptotic", "pyroptotic like", "like cell", "donado ca", "ca et", "the cleavage", "cleavage and", "and activation", "activation of", "gsdmd in", "in neutrophils", "neutrophils is", "is mediated", "mediated by", "by neutrophil", "neutrophil elastase", "ne or", "or elane", "is released", "released from", "from azurophil", "azurophil granules", "granules into", "the cytosol", "cytosol during", "during neutrophil", "neutrophil extracellular", "extracellular trap", "kambara h", ". further", "granzyme a", "from cytotoxic", "cytotoxic t", "t lymphocytes", "lymphocytes and", "and natural", "natural killer", "cells specifically", "specifically target", "target gsdmb", "gsdmb for", "for interdomain", "interdomain cleavage", "cleavage to", "to activate", "activate gsdmb", "gsdmb dependent", "dependent pyroptosis", "pyroptosis in", "in target", "target tumor", "tumor cells", "zhou z", ". similarly", "granzyme b", "can induce", "induce gsdme\u2011dependent", "gsdme\u2011dependent lytic", "lytic cell", "death in", "in tumor", "tumor targets", "targets via", "via the", "the casp3\u2011mediated", "casp3\u2011mediated cleavage", "of gsdme", "zhang z", "2020 .

              this", ".

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microbial infection", "microbial infection or", "infection or pathological", "or pathological stimuli", "stimuli such", "such as stroke", "as stroke or", "stroke or cancer", "cancer reviewed", "reviewed in shi", "in shi j", "shi j et", "j et al.", "et al. 2017", "2017 man", "man sm et", "sm et al.", "2017 tang", "tang d et", "d et al.", "et al. 2019", "2019 zheng", "zheng z &", "z & li", "& li g", "li g 2020", "g 2020 .", "2020 . the", ". the process", "the process of", "process of pyroptosis", "of pyroptosis protects", "pyroptosis protects the", "protects the host", "the host from", "host from microbial", "from microbial infection", "microbial infection but", "infection but can", "but can also", "can also lead", "also lead to", "lead to pathological", "to pathological inflammation", "pathological inflammation if", "inflammation if overactivated.", "if overactivated. the", "overactivated. the morphologic", "the morphologic characteristics", "morphologic characteristics of", "characteristics of pyroptosis", "of pyroptosis include", "pyroptosis include cell", "include cell swelling", "swelling rupture", "rupture of the", "of the cell", "the cell membrane", "cell membrane and", "membrane and release", "and release of", "release of intracellular", "of intracellular contents", "intracellular contents into", "contents into the", "into the extracellular", "the extracellular environment.", "extracellular environment. pyroptosis", "environment. pyroptosis is", "pyroptosis is also", "is also characterized", "also characterized by", "characterized by chromatin", "by chromatin condensation", "condensation however", "however this is", "this is not", "is not the", "not the key", "the key or", "key or universal", "or universal feature", "universal feature of", "feature of pyroptosis", "pyroptosis reviewed", "reviewed in man", "in man sm", "al. 2019 .", "2019 . pyroptosis", ". pyroptosis is", "pyroptosis is executed", "is executed by", "executed by proteins", "by proteins of", "proteins of the", "of the gasdermin", "the gasdermin family", "family which", "which mediate formation", "mediate formation of", "formation of membrane", "of membrane pores", "pores liu", "liu x et", "x et al.", "et al. 2016", "2016 ding", "ding j et", "2016 mulvihill", "mulvihill e et", "e et al.", "et al. 2018", "2018 broz", "broz p et", "p et al.", "et al. 2020", "al. 2020 .", "2020 . pyroptosis", ". pyroptosis can", "pyroptosis can be", "can be defined", "be defined as", "defined as gasdermin", "as gasdermin mediated", "gasdermin mediated programmed", "mediated programmed necrotic", "programmed necrotic cell", "necrotic cell death", "death shi", "2017 galluzzi", "galluzzi l et", "l et al.", "al. 2018 .", "2018 . the", ". the gasdermin", "gasdermin gsdm", "gsdm superfamily", "superfamily includes gsdma", "gsdma gsdmb", "gsdmb gsdmc", "gsdmc gsdmd", "gsdmd gsdme", "gsdme or", "dfna5 and", "pjvk dfnb59", "kovacs sb &", "sb & miao", "& miao ea", "miao ea 2018", "ea 2018 .", "2018 . each", ". each protein", "each protein contains", "protein contains an", "contains an n", "an n terminal", "n terminal domain", "terminal domain with", "domain with intrinsic", "with intrinsic necrotic", "intrinsic necrotic pore", "necrotic pore forming", "pore forming activity", "forming activity and", "activity and a", "and a c\u2011terminal", "a c\u2011terminal domain", "c\u2011terminal domain reported", "domain reported to", "reported to inhibit", "to inhibit cell", "inhibit cell death", "cell death through", "death through intramolecular", "through intramolecular domain", "intramolecular domain association", "association liu", "2016 liu", "liu z et", "z et al.", "2018 2019", "2019 kuang", "kuang s et", "s et al.", "al. 2017 .", "2017 . proteolytic", ". proteolytic cleavage", "proteolytic cleavage in", "cleavage in the", "in the linker", "the linker connecting", "linker connecting the", "connecting the n\u2011", "the n\u2011 and", "n\u2011 and c\u2011terminal", "and c\u2011terminal domains", "c\u2011terminal domains of", "domains of gasdermins", "of gasdermins releases", "gasdermins releases the", "releases the c\u2011terminus", "c\u2011terminus allowing", "allowing the gasdermin", "the gasdermin n\u2011terminus", "gasdermin n\u2011terminus to", "n\u2011terminus to translocate", "to translocate to", "translocate to the", "to the cell", "membrane and oligomerize", "and oligomerize to", "oligomerize to form", "to form pores", "pores shi", "et al. 2015", "2015 ding", "2016 sborgi", "sborgi l et", "2016 feng", "feng s et", "2018 yang", "yang j et", "2018 mulvihill", "2018 . although", ". although pjvk", "dfnb59 is", "is included to", "included to the", "to the gasdermin", "family it", "it is not", "is not known", "not known whether", "known whether pjvk", "whether pjvk is", "pjvk is cleaved", "is cleaved and", "cleaved and whether", "and whether the", "whether the full", "the full length", "full length or", "length or the", "or the n", "the n terminal", "n terminal portion", "terminal portion of", "portion of pjvk", "of pjvk is", "pjvk is responsible", "is responsible for", "responsible for forming", "for forming membrane", "forming membrane pores.", "membrane pores. the", "pores. the n\u2011terminal", "the n\u2011terminal fragments", "n\u2011terminal fragments of", "fragments of gsdms", "of gsdms strongly", "gsdms strongly bind", "strongly bind to", "bind to phosphatidylinositol", "to phosphatidylinositol phosphates", "phosphatidylinositol phosphates and", "phosphates and weakly", "and weakly to", "weakly to phosphatidylserine", "phosphatidylserine found", "found on the", "on the inner", "the inner leaflet", "inner leaflet of", "leaflet of the", "of the plasma", "the plasma membrane", "membrane liu", "2018 . gasdermins", ". gasdermins are", "gasdermins are also", "are also able", "also able to", "able to target", "to target cardiolipin", "cardiolipin which", "which is often", "is often found", "often found in", "found in mitochondrial", "in mitochondrial membranes", "mitochondrial membranes and", "membranes and membranes", "and membranes of", "membranes of bacteria", "bacteria liu", "2016 rogers", "rogers c et", "c et al.", "2019 . the", ". the size", "the size of", "size of the", "of the gsdmd", "the gsdmd pore", "gsdmd pore is", "pore is estimated", "is estimated to", "estimated to be", "to be 10\u201320", "be 10\u201320 nm", "nm ding", "al. 2016 .", "2016 . the", ". the pore\u2011forming", "the pore\u2011forming activity", "pore\u2011forming activity of", "activity of gsdms", "of gsdms in", "gsdms in the", "in the cell", "cell membrane facilitates", "membrane facilitates the", "facilitates the release", "the release of", "release of inflammatory", "of inflammatory molecules", "inflammatory molecules such", "molecules such as", "such as interleukin", "interleukin il", "il \u20111\u03b2 and", "\u20111\u03b2 and il\u201118", "il\u201118 mainly", "mainly in gsdmd", "in gsdmd mediated", "gsdmd mediated pyroptosis", "and eventually leads", "eventually leads to", "leads to cytolysis", "to cytolysis in", "cytolysis in mammalian", "in mammalian cells", "cells releasing", "releasing additional proinflammatory", "additional proinflammatory cellular", "proinflammatory cellular contents", "cellular contents including", "contents including danger", "including danger signals", "danger signals such", "signals such as", "such as high", "as high mobility", "high mobility group", "mobility group box\u20111", "box\u20111 hmgb1", "2015 he", "he w et", "w et al.", "2015 evavold", "evavold cl et", "cl et al.", "2017 semino", "semino c et", "2018 volchuk", "volchuk a et", "a et al.", "pyroptosis can occur", "can occur in", "occur in immune", "in immune cells", "immune cells such", "cells such as", "such as macrophages", "macrophages monocytes", "monocytes and dendritic", "and dendritic cells", "dendritic cells and", "cells and non\u2011immune", "and non\u2011immune cell", "non\u2011immune cell types", "cell types such", "types such as", "such as intestinal", "as intestinal epithelial", "intestinal epithelial cells", "cells trophoblasts", "trophoblasts and hepatocytes", "hepatocytes taabazuing", "taabazuing cy et", "cy et al.", "2017 li", "li h et", "h et al.", "2019 jia", "jia c et", "2019 . gsdme", ". gsdme can", "gsdme can be", "can be cleaved", "be cleaved by", "cleaved by caspase\u20113", "caspase\u20113 casp3", "casp3 to", "to induce pyroptosis", "induce pyroptosis downstream", "pyroptosis downstream of", "downstream of the", "of the \u201capoptotic\u201d", "the \u201capoptotic\u201d machinery", "machinery wang", "wang y et", "y et al.", "2017 rogers", "whereas gsdmd is", "gsdmd is cleaved", "is cleaved by", "cleaved by inflammatory", "by inflammatory casp1", "casp1 casp4", "casp4 and casp5", "and casp5 in", "casp5 in humans", "humans and", "casp1 casp11", "casp11 in mice", "in mice to", "mice to induce", "induce pyroptosis associated", "pyroptosis associated with", "associated with inflammasome", "with inflammasome activation", "activation shi", "2015 kayagaki", "kayagaki n et", "n et al.", "al. 2015 .", "2015 . casp3", ". casp3 cleavage", "casp3 cleavage of", "cleavage of gsdmd", "of gsdmd results", "gsdmd results in", "results in its", "in its inactivation", "inactivation taabazuing", "taabazuing et al.", "2017 . in", ". in mouse", "in mouse macrophages", "macrophages casp8", "casp8 can also", "can also cleave", "also cleave gsdmd", "cleave gsdmd and", "gsdmd and cause", "and cause pyroptosis", "cause pyroptosis when", "pyroptosis when tak1", "when tak1 is", "tak1 is inhibited", "inhibited malireddi", "malireddi r et", "r et al.", "2018 orning", "orning p et", "2018 sarhan", "sarhan j et", "and tak1 inhibition", "tak1 inhibition also", "inhibition also leads", "also leads to", "leads to gsdme", "to gsdme cleavage", "cleavage sarhan", "2018 . furthermore", "furthermore activated", "activated casp8 can", "casp8 can drive", "can drive inflammasome", "drive inflammasome independent", "inflammasome independent cleavage", "independent cleavage of", "cleavage of both", "of both pro", "both pro il", "pro il 1\u03b2", "il 1\u03b2 and", "1\u03b2 and gsdmd", "and gsdmd downstream", "gsdmd downstream of", "of the extrinsic", "the extrinsic cell", "extrinsic cell death", "cell death receptor", "death receptor signaling", "receptor signaling pathway", "signaling pathway switching", "pathway switching apoptotic", "switching apoptotic signaling", "apoptotic signaling to", "signaling to gsdmd", "to gsdmd dependent", "gsdmd dependent pyroptotic", "dependent pyroptotic like", "pyroptotic like cell", "like cell death", "death donado", "donado ca et", "ca et al.", ". the cleavage", "the cleavage and", "cleavage and activation", "and activation of", "activation of gsdmd", "of gsdmd in", "gsdmd in neutrophils", "in neutrophils is", "neutrophils is mediated", "is mediated by", "mediated by neutrophil", "by neutrophil elastase", "elastase ne", "ne or elane", "which is released", "is released from", "released from azurophil", "from azurophil granules", "azurophil granules into", "granules into the", "into the cytosol", "the cytosol during", "cytosol during neutrophil", "during neutrophil extracellular", "neutrophil extracellular trap", "trap net", "net formation", "formation kambara", "kambara h et", "2018 . further", "further granzyme", "a gzma", "gzma released", "released from cytotoxic", "from cytotoxic t", "cytotoxic t lymphocytes", "t lymphocytes and", "lymphocytes and natural", "and natural killer", "killer nk", "nk cells", "cells specifically target", "specifically target gsdmb", "target gsdmb for", "gsdmb for interdomain", "for interdomain cleavage", "interdomain cleavage to", "cleavage to activate", "to activate gsdmb", "activate gsdmb dependent", "gsdmb dependent pyroptosis", "dependent pyroptosis in", "pyroptosis in target", "in target tumor", "target tumor cells", "cells zhou", "zhou z et", "2020 . similarly", "similarly granzyme", "b gzmb", "gzmb released", "cells can", "can induce gsdme\u2011dependent", "induce gsdme\u2011dependent lytic", "gsdme\u2011dependent lytic cell", "lytic cell death", "cell death in", "death in tumor", "in tumor targets", "tumor targets via", "targets via the", "via the casp3\u2011mediated", "the casp3\u2011mediated cleavage", "casp3\u2011mediated cleavage of", "cleavage of gsdme", "gsdme zhang", "zhang z et", "al. 2020 .

              this", "2020 .

              this reactome", ".

              this reactome module", "reactome module describes", "module describes pyroptotic", "describes pyroptotic activities", "pyroptotic activities of", "activities of gsdmd", "of gsdmd and", "gsdmd and gsdme.", "and gsdme. while", "gsdme. while the", "while the n\u2011terminal", "the n\u2011terminal domains", "n\u2011terminal domains of", "domains of mammalian", "of mammalian gsdma", "gsdmb and", "and gsdmc also", "gsdmc also have", "also have the", "have the ability", "the ability to", "ability to form", "pores feng", "2018 ruan", "ruan j et", "their functions in", "functions in the", "in the induction", "the induction of", "induction of pyroptosis", "pyroptosis secretion", "secretion of proinflammatory", "of proinflammatory cytokines", "proinflammatory cytokines or", "cytokines or in", "or in bactericidal", "in bactericidal activity", "bactericidal activity in", "activity in host", "in host remain", "host remain to", "remain to be", "to be studied", "be studied and", "studied and are", "and are not", "are not covered", "not covered by", "covered by this", "by this reactome", "this reactome module.", "pyroptosis is a form", "is a form of", "a form of lytic", "form of lytic inflammatory", "of lytic inflammatory programmed", "lytic inflammatory programmed cell", "inflammatory programmed cell death", "programmed cell death that", "cell death that is", "death that is triggered", "that is triggered by", "is triggered by microbial", "triggered by microbial infection", "by microbial infection or", "microbial infection or pathological", "infection or pathological stimuli", "pathological stimuli such", "stimuli such as", "such as stroke or", "as stroke or cancer", "or cancer reviewed", "cancer reviewed in", "reviewed in shi j", "in shi j et", "shi j et al.", "j et al. 2017", "al. 2017 man", "2017 man sm", "man sm et al.", "sm et al. 2017", "al. 2017 tang", "2017 tang d", "tang d et al.", "d et al. 2019", "al. 2019 zheng", "2019 zheng z", "zheng z & li", "z & li g", "& li g 2020", "li g 2020 .", "g 2020 . the", "2020 . the process", ". the process of", "the process of pyroptosis", "process of pyroptosis protects", "of pyroptosis protects the", "pyroptosis protects the host", "protects the host from", "the host from microbial", "host from microbial infection", "from microbial infection but", "microbial infection but can", "infection but can also", "but can also lead", "can also lead to", "also lead to pathological", "lead to pathological inflammation", "to pathological inflammation if", "pathological inflammation if overactivated.", "inflammation if overactivated. the", "if overactivated. the morphologic", "overactivated. the morphologic characteristics", "the morphologic characteristics of", "morphologic characteristics of pyroptosis", "characteristics of pyroptosis include", "of pyroptosis include cell", "pyroptosis include cell swelling", "cell swelling rupture", "swelling rupture of", "rupture of the cell", "of the cell membrane", "the cell membrane and", "cell membrane and release", "membrane and release of", "and release of intracellular", "release of intracellular contents", "of intracellular contents into", "intracellular contents into the", "contents into the extracellular", "into the extracellular environment.", "the extracellular environment. pyroptosis", "extracellular environment. pyroptosis is", "environment. pyroptosis is also", "pyroptosis is also characterized", "is also characterized by", "also characterized by chromatin", "characterized by chromatin condensation", "chromatin condensation however", "condensation however this", "however this is not", "this is not the", "is not the key", "not the key or", "the key or universal", "key or universal feature", "or universal feature of", "universal feature of pyroptosis", "of pyroptosis reviewed", "pyroptosis reviewed in", "reviewed in man sm", "in man sm et", "et al. 2019 .", "al. 2019 . pyroptosis", "2019 . pyroptosis is", ". pyroptosis is executed", "pyroptosis is executed by", "is executed by proteins", "executed by proteins of", "by proteins of the", "proteins of the gasdermin", "of the gasdermin family", "gasdermin family which", "family which mediate", "which mediate formation of", "mediate formation of membrane", "formation of membrane pores", "membrane pores liu", "pores liu x", "liu x et al.", "x et al. 2016", "al. 2016 ding", "2016 ding j", "ding j et al.", "j et al. 2016", "al. 2016 mulvihill", "2016 mulvihill e", "mulvihill e et al.", "e et al. 2018", "al. 2018 broz", "2018 broz p", "broz p et al.", "p et al. 2020", "et al. 2020 .", "al. 2020 . pyroptosis", "2020 . pyroptosis can", ". pyroptosis can be", "pyroptosis can be defined", "can be defined as", "be defined as gasdermin", "defined as gasdermin mediated", "as gasdermin mediated programmed", "gasdermin mediated programmed necrotic", "mediated programmed necrotic cell", "programmed necrotic cell death", "cell death shi", "death shi j", "al. 2017 galluzzi", "2017 galluzzi l", "galluzzi l et al.", "l et al. 2018", "et al. 2018 .", "al. 2018 . the", "2018 . the gasdermin", "the gasdermin gsdm", "gsdm superfamily includes", "includes gsdma gsdmb", "gsdme or dfna5", "or dfna5 and", "dfna5 and pjvk", "and pjvk dfnb59", "dfnb59 kovacs", "kovacs sb & miao", "sb & miao ea", "& miao ea 2018", "miao ea 2018 .", "ea 2018 . each", "2018 . each protein", ". each protein contains", "each protein contains an", "protein contains an n", "contains an n terminal", "an n terminal domain", "n terminal domain with", "terminal domain with intrinsic", "domain with intrinsic necrotic", "with intrinsic necrotic pore", "intrinsic necrotic pore forming", "necrotic pore forming activity", "pore forming activity and", "forming activity and a", "activity and a c\u2011terminal", "and a c\u2011terminal domain", "a c\u2011terminal domain reported", "c\u2011terminal domain reported to", "domain reported to inhibit", "reported to inhibit cell", "to inhibit cell death", "inhibit cell death through", "cell death through intramolecular", "death through intramolecular domain", "through intramolecular domain association", "domain association liu", "association liu x", "al. 2016 liu", "2016 liu z", "liu z et al.", "z et al. 2018", "al. 2018 2019", "2019 kuang s", "kuang s et al.", "s et al. 2017", "et al. 2017 .", "al. 2017 . proteolytic", "2017 . proteolytic cleavage", ". proteolytic cleavage in", "proteolytic cleavage in the", "cleavage in the linker", "in the linker connecting", "the linker connecting the", "linker connecting the n\u2011", "connecting the n\u2011 and", "the n\u2011 and c\u2011terminal", "n\u2011 and c\u2011terminal domains", "and c\u2011terminal domains of", "c\u2011terminal domains of gasdermins", "domains of gasdermins releases", "of gasdermins releases the", "gasdermins releases the c\u2011terminus", "the c\u2011terminus allowing", "c\u2011terminus allowing the", "allowing the gasdermin n\u2011terminus", "the gasdermin n\u2011terminus to", "gasdermin n\u2011terminus to translocate", "n\u2011terminus to translocate to", "to translocate to the", "translocate to the cell", "to the cell membrane", "cell membrane and oligomerize", "membrane and oligomerize to", "and oligomerize to form", "oligomerize to form pores", "form pores shi", "pores shi j", "j et al. 2015", "al. 2015 ding", "2015 ding j", "al. 2016 sborgi", "2016 sborgi l", "sborgi l et al.", "l et al. 2016", "al. 2016 feng", "2016 feng s", "feng s et al.", "s et al. 2018", "al. 2018 yang", "2018 yang j", "yang j et al.", "j et al. 2018", "al. 2018 mulvihill", "2018 mulvihill e", "al. 2018 . although", "2018 . although pjvk", "although pjvk dfnb59", "dfnb59 is included", "is included to the", "included to the gasdermin", "to the gasdermin family", "gasdermin family it", "family it is", "it is not known", "is not known whether", "not known whether pjvk", "known whether pjvk is", "whether pjvk is cleaved", "pjvk is cleaved and", "is cleaved and whether", "cleaved and whether the", "and whether the full", "whether the full length", "the full length or", "full length or the", "length or the n", "or the n terminal", "the n terminal portion", "n terminal portion of", "terminal portion of pjvk", "portion of pjvk is", "of pjvk is responsible", "pjvk is responsible for", "is responsible for forming", "responsible for forming membrane", "for forming membrane pores.", "forming membrane pores. the", "membrane pores. the n\u2011terminal", "pores. the n\u2011terminal fragments", "the n\u2011terminal fragments of", "n\u2011terminal fragments of gsdms", "fragments of gsdms strongly", "of gsdms strongly bind", "gsdms strongly bind to", "strongly bind to phosphatidylinositol", "bind to phosphatidylinositol phosphates", "to phosphatidylinositol phosphates and", "phosphatidylinositol phosphates and weakly", "phosphates and weakly to", "and weakly to phosphatidylserine", "to phosphatidylserine found", "phosphatidylserine found on", "found on the inner", "on the inner leaflet", "the inner leaflet of", "inner leaflet of the", "leaflet of the plasma", "of the plasma membrane", "plasma membrane liu", "membrane liu x", "al. 2018 . gasdermins", "2018 . gasdermins are", ". gasdermins are also", "gasdermins are also able", "are also able to", "also able to target", "able to target cardiolipin", "target cardiolipin which", "cardiolipin which is", "which is often found", "is often found in", "often found in mitochondrial", "found in mitochondrial membranes", "in mitochondrial membranes and", "mitochondrial membranes and membranes", "membranes and membranes of", "and membranes of bacteria", "of bacteria liu", "bacteria liu x", "al. 2016 rogers", "2016 rogers c", "rogers c et al.", "c et al. 2019", "al. 2019 . the", "2019 . the size", ". the size of", "the size of the", "size of the gsdmd", "of the gsdmd pore", "the gsdmd pore is", "gsdmd pore is estimated", "pore is estimated to", "is estimated to be", "estimated to be 10\u201320", "to be 10\u201320 nm", "10\u201320 nm ding", "nm ding j", "et al. 2016 .", "al. 2016 . the", "2016 . the pore\u2011forming", ". the pore\u2011forming activity", "the pore\u2011forming activity of", "pore\u2011forming activity of gsdms", "activity of gsdms in", "of gsdms in the", "gsdms in the cell", "in the cell membrane", "the cell membrane facilitates", "cell membrane facilitates the", "membrane facilitates the release", "facilitates the release of", "the release of inflammatory", "release of inflammatory molecules", "of inflammatory molecules such", "inflammatory molecules such as", "molecules such as interleukin", "as interleukin il", "interleukin il \u20111\u03b2", "il \u20111\u03b2 and il\u201118", "and il\u201118 mainly", "il\u201118 mainly in", "mainly in gsdmd mediated", "in gsdmd mediated pyroptosis", "pyroptosis and", "and eventually leads to", "eventually leads to cytolysis", "leads to cytolysis in", "to cytolysis in mammalian", "cytolysis in mammalian cells", "mammalian cells releasing", "cells releasing additional", "releasing additional proinflammatory cellular", "additional proinflammatory cellular contents", "proinflammatory cellular contents including", "cellular contents including danger", "contents including danger signals", "including danger signals such", "danger signals such as", "signals such as high", "such as high mobility", "as high mobility group", "high mobility group box\u20111", "group box\u20111 hmgb1", "hmgb1 shi", "al. 2015 he", "2015 he w", "he w et al.", "w et al. 2015", "al. 2015 evavold", "2015 evavold cl", "evavold cl et al.", "cl et al. 2017", "al. 2017 semino", "2017 semino c", "semino c et al.", "c et al. 2018", "al. 2018 volchuk", "2018 volchuk a", "volchuk a et al.", "a et al. 2020", ". pyroptosis can occur", "pyroptosis can occur in", "can occur in immune", "occur in immune cells", "in immune cells such", "immune cells such as", "cells such as macrophages", "as macrophages monocytes", "macrophages monocytes and", "monocytes and dendritic cells", "and dendritic cells and", "dendritic cells and non\u2011immune", "cells and non\u2011immune cell", "and non\u2011immune cell types", "non\u2011immune cell types such", "cell types such as", "types such as intestinal", "such as intestinal epithelial", "as intestinal epithelial cells", "epithelial cells trophoblasts", "cells trophoblasts and", "and hepatocytes taabazuing", "hepatocytes taabazuing cy", "taabazuing cy et al.", "cy et al. 2017", "al. 2017 li", "2017 li h", "li h et al.", "h et al. 2019", "al. 2019 jia", "2019 jia c", "jia c et al.", "al. 2019 . gsdme", "2019 . gsdme can", ". gsdme can be", "gsdme can be cleaved", "can be cleaved by", "be cleaved by caspase\u20113", "by caspase\u20113 casp3", "casp3 to induce", "to induce pyroptosis downstream", "induce pyroptosis downstream of", "pyroptosis downstream of the", "downstream of the \u201capoptotic\u201d", "of the \u201capoptotic\u201d machinery", "\u201capoptotic\u201d machinery wang", "machinery wang y", "wang y et al.", "y et al. 2017", "al. 2017 rogers", "2017 rogers c", "c et al. 2017", "2017 whereas", "whereas gsdmd is cleaved", "gsdmd is cleaved by", "is cleaved by inflammatory", "cleaved by inflammatory casp1", "inflammatory casp1 casp4", "casp1 casp4 and", "casp4 and casp5 in", "and casp5 in humans", "in humans and", "humans and casp1", "and casp1 casp11", "casp1 casp11 in", "casp11 in mice to", "in mice to induce", "mice to induce pyroptosis", "to induce pyroptosis associated", "induce pyroptosis associated with", "pyroptosis associated with inflammasome", "associated with inflammasome activation", "inflammasome activation shi", "activation shi j", "al. 2015 kayagaki", "2015 kayagaki n", "kayagaki n et al.", "n et al. 2015", "et al. 2015 .", "al. 2015 . casp3", "2015 . casp3 cleavage", ". casp3 cleavage of", "casp3 cleavage of gsdmd", "cleavage of gsdmd results", "of gsdmd results in", "gsdmd results in its", "results in its inactivation", "its inactivation taabazuing", "inactivation taabazuing et", "taabazuing et al. 2017", "al. 2017 . in", "2017 . in mouse", ". in mouse macrophages", "mouse macrophages casp8", "macrophages casp8 can", "casp8 can also cleave", "can also cleave gsdmd", "also cleave gsdmd and", "cleave gsdmd and cause", "gsdmd and cause pyroptosis", "and cause pyroptosis when", "cause pyroptosis when tak1", "pyroptosis when tak1 is", "when tak1 is inhibited", "is inhibited malireddi", "inhibited malireddi r", "malireddi r et al.", "r et al. 2018", "al. 2018 orning", "2018 orning p", "orning p et al.", "p et al. 2018", "al. 2018 sarhan", "2018 sarhan j", "sarhan j et al.", "2018 and", "and tak1 inhibition also", "tak1 inhibition also leads", "inhibition also leads to", "also leads to gsdme", "leads to gsdme cleavage", "gsdme cleavage sarhan", "cleavage sarhan j", "al. 2018 . furthermore", ". furthermore activated", "furthermore activated casp8", "activated casp8 can drive", "casp8 can drive inflammasome", "can drive inflammasome independent", "drive inflammasome independent cleavage", "inflammasome independent cleavage of", "independent cleavage of both", "cleavage of both pro", "of both pro il", "both pro il 1\u03b2", "pro il 1\u03b2 and", "il 1\u03b2 and gsdmd", "1\u03b2 and gsdmd downstream", "and gsdmd downstream of", "gsdmd downstream of the", "downstream of the extrinsic", "of the extrinsic cell", "the extrinsic cell death", "extrinsic cell death receptor", "cell death receptor signaling", "death receptor signaling pathway", "receptor signaling pathway switching", "signaling pathway switching apoptotic", "pathway switching apoptotic signaling", "switching apoptotic signaling to", "apoptotic signaling to gsdmd", "signaling to gsdmd dependent", "to gsdmd dependent pyroptotic", "gsdmd dependent pyroptotic like", "dependent pyroptotic like cell", "pyroptotic like cell death", "cell death donado", "death donado ca", "donado ca et al.", "ca et al. 2020", "al. 2020 . the", "2020 . the cleavage", ". the cleavage and", "the cleavage and activation", "cleavage and activation of", "and activation of gsdmd", "activation of gsdmd in", "of gsdmd in neutrophils", "gsdmd in neutrophils is", "in neutrophils is mediated", "neutrophils is mediated by", "is mediated by neutrophil", "mediated by neutrophil elastase", "neutrophil elastase ne", "elastase ne or", "elane which", "which is released from", "is released from azurophil", "released from azurophil granules", "from azurophil granules into", "azurophil granules into the", "granules into the cytosol", "into the cytosol during", "the cytosol during neutrophil", "cytosol during neutrophil extracellular", "during neutrophil extracellular trap", "extracellular trap net", "formation kambara h", "kambara h et al.", "h et al. 2018", "al. 2018 . further", ". further granzyme", "further granzyme a", "granzyme a gzma", "gzma released from", "released from cytotoxic t", "from cytotoxic t lymphocytes", "cytotoxic t lymphocytes and", "t lymphocytes and natural", "lymphocytes and natural killer", "natural killer nk", "nk cells specifically", "cells specifically target gsdmb", "specifically target gsdmb for", "target gsdmb for interdomain", "gsdmb for interdomain cleavage", "for interdomain cleavage to", "interdomain cleavage to activate", "cleavage to activate gsdmb", "to activate gsdmb dependent", "activate gsdmb dependent pyroptosis", "gsdmb dependent pyroptosis in", "dependent pyroptosis in target", "pyroptosis in target tumor", "in target tumor cells", "tumor cells zhou", "cells zhou z", "zhou z et al.", "z et al. 2020", "al. 2020 . similarly", ". similarly granzyme", "similarly granzyme b", "granzyme b gzmb", "gzmb released from", "cells can induce", "can induce gsdme\u2011dependent lytic", "induce gsdme\u2011dependent lytic cell", "gsdme\u2011dependent lytic cell death", "lytic cell death in", "cell death in tumor", "death in tumor targets", "in tumor targets via", "tumor targets via the", "targets via the casp3\u2011mediated", "via the casp3\u2011mediated cleavage", "the casp3\u2011mediated cleavage of", "casp3\u2011mediated cleavage of gsdme", "of gsdme zhang", "gsdme zhang z", "zhang z et al.", "et al. 2020 .

              this", "al. 2020 .

              this reactome", "2020 .

              this reactome module", ".

              this reactome module describes", "reactome module describes pyroptotic", "module describes pyroptotic activities", "describes pyroptotic activities of", "pyroptotic activities of gsdmd", "activities of gsdmd and", "of gsdmd and gsdme.", "gsdmd and gsdme. while", "and gsdme. while the", "gsdme. while the n\u2011terminal", "while the n\u2011terminal domains", "the n\u2011terminal domains of", "n\u2011terminal domains of mammalian", "domains of mammalian gsdma", "mammalian gsdma gsdmb", "gsdmb and gsdmc", "and gsdmc also have", "gsdmc also have the", "also have the ability", "have the ability to", "the ability to form", "ability to form pores", "form pores feng", "pores feng s", "al. 2018 ruan", "2018 ruan j", "ruan j et al.", "2018 their", "their functions in the", "functions in the induction", "in the induction of", "the induction of pyroptosis", "of pyroptosis secretion", "pyroptosis secretion of", "secretion of proinflammatory cytokines", "of proinflammatory cytokines or", "proinflammatory cytokines or in", "cytokines or in bactericidal", "or in bactericidal activity", "in bactericidal activity in", "bactericidal activity in host", "activity in host remain", "in host remain to", "host remain to be", "remain to be studied", "to be studied and", "be studied and are", "studied and are not", "and are not covered", "are not covered by", "not covered by this", "covered by this reactome", "by this reactome module.", "pyroptosis is a form of", "is a form of lytic", "a form of lytic inflammatory", "form of lytic inflammatory programmed", "of lytic inflammatory programmed cell", "lytic inflammatory programmed cell death", "inflammatory programmed cell death that", "programmed cell death that is", "cell death that is triggered", "death that is triggered by", "that is triggered by microbial", "is triggered by microbial infection", "triggered by microbial infection or", "by microbial infection or pathological", "microbial infection or pathological stimuli", "or pathological stimuli such", "pathological stimuli such as", "stimuli such as stroke", "such as stroke or cancer", "stroke or cancer reviewed", "or cancer reviewed in", "cancer reviewed in shi", "reviewed in shi j et", "in shi j et al.", "shi j et al. 2017", "et al. 2017 man", "al. 2017 man sm", "2017 man sm et", "man sm et al. 2017", "et al. 2017 tang", "al. 2017 tang d", "2017 tang d et", "tang d et al. 2019", "et al. 2019 zheng", "al. 2019 zheng z", "2019 zheng z &", "zheng z & li g", "z & li g 2020", "& li g 2020 .", "li g 2020 . the", "g 2020 . the process", "2020 . the process of", ". the process of pyroptosis", "the process of pyroptosis protects", "process of pyroptosis protects the", "of pyroptosis protects the host", "pyroptosis protects the host from", "protects the host from microbial", "the host from microbial infection", "host from microbial infection but", "from microbial infection but can", "microbial infection but can also", "infection but can also lead", "but can also lead to", "can also lead to pathological", "also lead to pathological inflammation", "lead to pathological inflammation if", "to pathological inflammation if overactivated.", "pathological inflammation if overactivated. the", "inflammation if overactivated. the morphologic", "if overactivated. the morphologic characteristics", "overactivated. the morphologic characteristics of", "the morphologic characteristics of pyroptosis", "morphologic characteristics of pyroptosis include", "characteristics of pyroptosis include cell", "of pyroptosis include cell swelling", "include cell swelling rupture", "cell swelling rupture of", "swelling rupture of the", "rupture of the cell membrane", "of the cell membrane and", "the cell membrane and release", "cell membrane and release of", "membrane and release of intracellular", "and release of intracellular contents", "release of intracellular contents into", "of intracellular contents into the", "intracellular contents into the extracellular", "contents into the extracellular environment.", "into the extracellular environment. pyroptosis", "the extracellular environment. pyroptosis is", "extracellular environment. pyroptosis is also", "environment. pyroptosis is also characterized", "pyroptosis is also characterized by", "is also characterized by chromatin", "also characterized by chromatin condensation", "by chromatin condensation however", "chromatin condensation however this", "condensation however this is", "however this is not the", "this is not the key", "is not the key or", "not the key or universal", "the key or universal feature", "key or universal feature of", "or universal feature of pyroptosis", "feature of pyroptosis reviewed", "of pyroptosis reviewed in", "pyroptosis reviewed in man", "reviewed in man sm et", "in man sm et al.", "d et al. 2019 .", "et al. 2019 . pyroptosis", "al. 2019 . pyroptosis is", "2019 . pyroptosis is executed", ". pyroptosis is executed by", "pyroptosis is executed by proteins", "is executed by proteins of", "executed by proteins of the", "by proteins of the gasdermin", "proteins of the gasdermin family", "the gasdermin family which", "gasdermin family which mediate", "family which mediate formation", "which mediate formation of membrane", "mediate formation of membrane pores", "of membrane pores liu", "membrane pores liu x", "pores liu x et", "liu x et al. 2016", "et al. 2016 ding", "al. 2016 ding j", "2016 ding j et", "ding j et al. 2016", "et al. 2016 mulvihill", "al. 2016 mulvihill e", "2016 mulvihill e et", "mulvihill e et al. 2018", "et al. 2018 broz", "al. 2018 broz p", "2018 broz p et", "broz p et al. 2020", "p et al. 2020 .", "et al. 2020 . pyroptosis", "al. 2020 . pyroptosis can", "2020 . pyroptosis can be", ". pyroptosis can be defined", "pyroptosis can be defined as", "can be defined as gasdermin", "be defined as gasdermin mediated", "defined as gasdermin mediated programmed", "as gasdermin mediated programmed necrotic", "gasdermin mediated programmed necrotic cell", "mediated programmed necrotic cell death", "necrotic cell death shi", "cell death shi j", "death shi j et", "et al. 2017 galluzzi", "al. 2017 galluzzi l", "2017 galluzzi l et", "galluzzi l et al. 2018", "l et al. 2018 .", "et al. 2018 . the", "al. 2018 . the gasdermin", ". the gasdermin gsdm", "gasdermin gsdm superfamily", "gsdm superfamily includes gsdma", "superfamily includes gsdma gsdmb", "gsdma gsdmb gsdmc", "gsdmb gsdmc gsdmd", "gsdmc gsdmd gsdme", "gsdmd gsdme or", "or dfna5 and pjvk", "dfnb59 kovacs sb", "kovacs sb & miao ea", "sb & miao ea 2018", "& miao ea 2018 .", "miao ea 2018 . each", "ea 2018 . each protein", "2018 . each protein contains", ". each protein contains an", "each protein contains an n", "protein contains an n terminal", "contains an n terminal domain", "an n terminal domain with", "n terminal domain with intrinsic", "terminal domain with intrinsic necrotic", "domain with intrinsic necrotic pore", "with intrinsic necrotic pore forming", "intrinsic necrotic pore forming activity", "necrotic pore forming activity and", "pore forming activity and a", "forming activity and a c\u2011terminal", "activity and a c\u2011terminal domain", "and a c\u2011terminal domain reported", "a c\u2011terminal domain reported to", "c\u2011terminal domain reported to inhibit", "domain reported to inhibit cell", "reported to inhibit cell death", "to inhibit cell death through", "inhibit cell death through intramolecular", "cell death through intramolecular domain", "death through intramolecular domain association", "intramolecular domain association liu", "domain association liu x", "association liu x et", "et al. 2016 liu", "al. 2016 liu z", "2016 liu z et", "liu z et al. 2018", "et al. 2018 2019", "2018 2019 kuang", "2019 kuang s et", "kuang s et al. 2017", "s et al. 2017 .", "et al. 2017 . proteolytic", "al. 2017 . proteolytic cleavage", "2017 . proteolytic cleavage in", ". proteolytic cleavage in the", "proteolytic cleavage in the linker", "cleavage in the linker connecting", "in the linker connecting the", "the linker connecting the n\u2011", "linker connecting the n\u2011 and", "connecting the n\u2011 and c\u2011terminal", "the n\u2011 and c\u2011terminal domains", "n\u2011 and c\u2011terminal domains of", "and c\u2011terminal domains of gasdermins", "c\u2011terminal domains of gasdermins releases", "domains of gasdermins releases the", "of gasdermins releases the c\u2011terminus", "releases the c\u2011terminus allowing", "the c\u2011terminus allowing the", "c\u2011terminus allowing the gasdermin", "allowing the gasdermin n\u2011terminus to", "the gasdermin n\u2011terminus to translocate", "gasdermin n\u2011terminus to translocate to", "n\u2011terminus to translocate to the", "to translocate to the cell", "translocate to the cell membrane", "to the cell membrane and", "the cell membrane and oligomerize", "cell membrane and oligomerize to", "membrane and oligomerize to form", "and oligomerize to form pores", "to form pores shi", "form pores shi j", "pores shi j et", "shi j et al. 2015", "et al. 2015 ding", "al. 2015 ding j", "2015 ding j et", "et al. 2016 sborgi", "al. 2016 sborgi l", "2016 sborgi l et", "sborgi l et al. 2016", "et al. 2016 feng", "al. 2016 feng s", "2016 feng s et", "feng s et al. 2018", "et al. 2018 yang", "al. 2018 yang j", "2018 yang j et", "yang j et al. 2018", "et al. 2018 mulvihill", "al. 2018 mulvihill e", "2018 mulvihill e et", "e et al. 2018 .", "et al. 2018 . although", "al. 2018 . although pjvk", ". although pjvk dfnb59", "pjvk dfnb59 is", "dfnb59 is included to", "is included to the gasdermin", "included to the gasdermin family", "the gasdermin family it", "gasdermin family it is", "family it is not", "it is not known whether", "is not known whether pjvk", "not known whether pjvk is", "known whether pjvk is cleaved", "whether pjvk is cleaved and", "pjvk is cleaved and whether", "is cleaved and whether the", "cleaved and whether the full", "and whether the full length", "whether the full length or", "the full length or the", "full length or the n", "length or the n terminal", "or the n terminal portion", "the n terminal portion of", "n terminal portion of pjvk", "terminal portion of pjvk is", "portion of pjvk is responsible", "of pjvk is responsible for", "pjvk is responsible for forming", "is responsible for forming membrane", "responsible for forming membrane pores.", "for forming membrane pores. the", "forming membrane pores. the n\u2011terminal", "membrane pores. the n\u2011terminal fragments", "pores. the n\u2011terminal fragments of", "the n\u2011terminal fragments of gsdms", "n\u2011terminal fragments of gsdms strongly", "fragments of gsdms strongly bind", "of gsdms strongly bind to", "gsdms strongly bind to phosphatidylinositol", "strongly bind to phosphatidylinositol phosphates", "bind to phosphatidylinositol phosphates and", "to phosphatidylinositol phosphates and weakly", "phosphatidylinositol phosphates and weakly to", "phosphates and weakly to phosphatidylserine", "weakly to phosphatidylserine found", "to phosphatidylserine found on", "phosphatidylserine found on the", "found on the inner leaflet", "on the inner leaflet of", "the inner leaflet of the", "inner leaflet of the plasma", "leaflet of the plasma membrane", "the plasma membrane liu", "plasma membrane liu x", "membrane liu x et", "et al. 2018 . gasdermins", "al. 2018 . gasdermins are", "2018 . gasdermins are also", ". gasdermins are also able", "gasdermins are also able to", "are also able to target", "also able to target cardiolipin", "to target cardiolipin which", "target cardiolipin which is", "cardiolipin which is often", "which is often found in", "is often found in mitochondrial", "often found in mitochondrial membranes", "found in mitochondrial membranes and", "in mitochondrial membranes and membranes", "mitochondrial membranes and membranes of", "membranes and membranes of bacteria", "membranes of bacteria liu", "of bacteria liu x", "bacteria liu x et", "et al. 2016 rogers", "al. 2016 rogers c", "2016 rogers c et", "rogers c et al. 2019", "c et al. 2019 .", "et al. 2019 . the", "al. 2019 . the size", "2019 . the size of", ". the size of the", "the size of the gsdmd", "size of the gsdmd pore", "of the gsdmd pore is", "the gsdmd pore is estimated", "gsdmd pore is estimated to", "pore is estimated to be", "is estimated to be 10\u201320", "estimated to be 10\u201320 nm", "be 10\u201320 nm ding", "10\u201320 nm ding j", "nm ding j et", "l et al. 2016 .", "et al. 2016 . the", "al. 2016 . the pore\u2011forming", "2016 . the pore\u2011forming activity", ". the pore\u2011forming activity of", "the pore\u2011forming activity of gsdms", "pore\u2011forming activity of gsdms in", "activity of gsdms in the", "of gsdms in the cell", "gsdms in the cell membrane", "in the cell membrane facilitates", "the cell membrane facilitates the", "cell membrane facilitates the release", "membrane facilitates the release of", "facilitates the release of inflammatory", "the release of inflammatory molecules", "release of inflammatory molecules such", "of inflammatory molecules such as", "inflammatory molecules such as interleukin", "such as interleukin il", "as interleukin il \u20111\u03b2", "interleukin il \u20111\u03b2 and", "\u20111\u03b2 and il\u201118 mainly", "and il\u201118 mainly in", "il\u201118 mainly in gsdmd", "mainly in gsdmd mediated pyroptosis", "mediated pyroptosis and", "pyroptosis and eventually", "and eventually leads to cytolysis", "eventually leads to cytolysis in", "leads to cytolysis in mammalian", "to cytolysis in mammalian cells", "in mammalian cells releasing", "mammalian cells releasing additional", "cells releasing additional proinflammatory", "releasing additional proinflammatory cellular contents", "additional proinflammatory cellular contents including", "proinflammatory cellular contents including danger", "cellular contents including danger signals", "contents including danger signals such", "including danger signals such as", "danger signals such as high", "signals such as high mobility", "such as high mobility group", "as high mobility group box\u20111", "mobility group box\u20111 hmgb1", "hmgb1 shi j", "et al. 2015 he", "al. 2015 he w", "2015 he w et", "he w et al. 2015", "et al. 2015 evavold", "al. 2015 evavold cl", "2015 evavold cl et", "evavold cl et al. 2017", "et al. 2017 semino", "al. 2017 semino c", "2017 semino c et", "semino c et al. 2018", "et al. 2018 volchuk", "al. 2018 volchuk a", "2018 volchuk a et", "volchuk a et al. 2020", "a et al. 2020 .", "2020 . pyroptosis can occur", ". pyroptosis can occur in", "pyroptosis can occur in immune", "can occur in immune cells", "occur in immune cells such", "in immune cells such as", "immune cells such as macrophages", "such as macrophages monocytes", "as macrophages monocytes and", "macrophages monocytes and dendritic", "monocytes and dendritic cells and", "and dendritic cells and non\u2011immune", "dendritic cells and non\u2011immune cell", "cells and non\u2011immune cell types", "and non\u2011immune cell types such", "non\u2011immune cell types such as", "cell types such as intestinal", "types such as intestinal epithelial", "such as intestinal epithelial cells", "intestinal epithelial cells trophoblasts", "epithelial cells trophoblasts and", "cells trophoblasts and hepatocytes", "trophoblasts and hepatocytes taabazuing", "and hepatocytes taabazuing cy", "hepatocytes taabazuing cy et", "taabazuing cy et al. 2017", "et al. 2017 li", "al. 2017 li h", "2017 li h et", "li h et al. 2019", "et al. 2019 jia", "al. 2019 jia c", "2019 jia c et", "jia c et al. 2019", "et al. 2019 . gsdme", "al. 2019 . gsdme can", "2019 . gsdme can be", ". gsdme can be cleaved", "gsdme can be cleaved by", "can be cleaved by caspase\u20113", "cleaved by caspase\u20113 casp3", "caspase\u20113 casp3 to", "casp3 to induce pyroptosis", "to induce pyroptosis downstream of", "induce pyroptosis downstream of the", "pyroptosis downstream of the \u201capoptotic\u201d", "downstream of the \u201capoptotic\u201d machinery", "the \u201capoptotic\u201d machinery wang", "\u201capoptotic\u201d machinery wang y", "machinery wang y et", "wang y et al. 2017", "et al. 2017 rogers", "al. 2017 rogers c", "2017 rogers c et", "rogers c et al. 2017", "al. 2017 whereas", "2017 whereas gsdmd", "whereas gsdmd is cleaved by", "gsdmd is cleaved by inflammatory", "is cleaved by inflammatory casp1", "by inflammatory casp1 casp4", "inflammatory casp1 casp4 and", "casp1 casp4 and casp5", "casp4 and casp5 in humans", "casp5 in humans and", "in humans and casp1", "and casp1 casp11 in", "casp1 casp11 in mice", "casp11 in mice to induce", "in mice to induce pyroptosis", "mice to induce pyroptosis associated", "to induce pyroptosis associated with", "induce pyroptosis associated with inflammasome", "pyroptosis associated with inflammasome activation", "with inflammasome activation shi", "inflammasome activation shi j", "activation shi j et", "et al. 2015 kayagaki", "al. 2015 kayagaki n", "2015 kayagaki n et", "kayagaki n et al. 2015", "n et al. 2015 .", "et al. 2015 . casp3", "al. 2015 . casp3 cleavage", "2015 . casp3 cleavage of", ". casp3 cleavage of gsdmd", "casp3 cleavage of gsdmd results", "cleavage of gsdmd results in", "of gsdmd results in its", "gsdmd results in its inactivation", "in its inactivation taabazuing", "its inactivation taabazuing et", "inactivation taabazuing et al.", "taabazuing et al. 2017 .", "et al. 2017 . in", "al. 2017 . in mouse", "2017 . in mouse macrophages", "in mouse macrophages casp8", "mouse macrophages casp8 can", "macrophages casp8 can also", "casp8 can also cleave gsdmd", "can also cleave gsdmd and", "also cleave gsdmd and cause", "cleave gsdmd and cause pyroptosis", "gsdmd and cause pyroptosis when", "and cause pyroptosis when tak1", "cause pyroptosis when tak1 is", "pyroptosis when tak1 is inhibited", "tak1 is inhibited malireddi", "is inhibited malireddi r", "inhibited malireddi r et", "malireddi r et al. 2018", "et al. 2018 orning", "al. 2018 orning p", "2018 orning p et", "orning p et al. 2018", "et al. 2018 sarhan", "al. 2018 sarhan j", "2018 sarhan j et", "sarhan j et al. 2018", "al. 2018 and", "2018 and tak1", "and tak1 inhibition also leads", "tak1 inhibition also leads to", "inhibition also leads to gsdme", "also leads to gsdme cleavage", "to gsdme cleavage sarhan", "gsdme cleavage sarhan j", "cleavage sarhan j et", "j et al. 2018 .", "et al. 2018 . furthermore", "2018 . furthermore activated", ". furthermore activated casp8", "furthermore activated casp8 can", "activated casp8 can drive inflammasome", "casp8 can drive inflammasome independent", "can drive inflammasome independent cleavage", "drive inflammasome independent cleavage of", "inflammasome independent cleavage of both", "independent cleavage of both pro", "cleavage of both pro il", "of both pro il 1\u03b2", "both pro il 1\u03b2 and", "pro il 1\u03b2 and gsdmd", "il 1\u03b2 and gsdmd downstream", "1\u03b2 and gsdmd downstream of", "and gsdmd downstream of the", "gsdmd downstream of the extrinsic", "downstream of the extrinsic cell", "of the extrinsic cell death", "the extrinsic cell death receptor", "extrinsic cell death receptor signaling", "cell death receptor signaling pathway", "death receptor signaling pathway switching", "receptor signaling pathway switching apoptotic", "signaling pathway switching apoptotic signaling", "pathway switching apoptotic signaling to", "switching apoptotic signaling to gsdmd", "apoptotic signaling to gsdmd dependent", "signaling to gsdmd dependent pyroptotic", "to gsdmd dependent pyroptotic like", "gsdmd dependent pyroptotic like cell", "dependent pyroptotic like cell death", "like cell death donado", "cell death donado ca", "death donado ca et", "donado ca et al. 2020", "ca et al. 2020 .", "et al. 2020 . the", "al. 2020 . the cleavage", "2020 . the cleavage and", ". the cleavage and activation", "the cleavage and activation of", "cleavage and activation of gsdmd", "and activation of gsdmd in", "activation of gsdmd in neutrophils", "of gsdmd in neutrophils is", "gsdmd in neutrophils is mediated", "in neutrophils is mediated by", "neutrophils is mediated by neutrophil", "is mediated by neutrophil elastase", "by neutrophil elastase ne", "neutrophil elastase ne or", "elastase ne or elane", "or elane which", "elane which is", "which is released from azurophil", "is released from azurophil granules", "released from azurophil granules into", "from azurophil granules into the", "azurophil granules into the cytosol", "granules into the cytosol during", "into the cytosol during neutrophil", "the cytosol during neutrophil extracellular", "cytosol during neutrophil extracellular trap", "neutrophil extracellular trap net", "trap net formation", "net formation kambara", "formation kambara h et", "kambara h et al. 2018", "h et al. 2018 .", "et al. 2018 . further", "2018 . further granzyme", ". further granzyme a", "a gzma released", "gzma released from cytotoxic", "released from cytotoxic t lymphocytes", "from cytotoxic t lymphocytes and", "cytotoxic t lymphocytes and natural", "t lymphocytes and natural killer", "and natural killer nk", "killer nk cells", "nk cells specifically target", "cells specifically target gsdmb for", "specifically target gsdmb for interdomain", "target gsdmb for interdomain cleavage", "gsdmb for interdomain cleavage to", "for interdomain cleavage to activate", "interdomain cleavage to activate gsdmb", "cleavage to activate gsdmb dependent", "to activate gsdmb dependent pyroptosis", "activate gsdmb dependent pyroptosis in", "gsdmb dependent pyroptosis in target", "dependent pyroptosis in target tumor", "pyroptosis in target tumor cells", "target tumor cells zhou", "tumor cells zhou z", "cells zhou z et", "zhou z et al. 2020", "z et al. 2020 .", "et al. 2020 . similarly", "2020 . similarly granzyme", ". similarly granzyme b", "b gzmb released", "gzmb released from cytotoxic", "nk cells can", "cells can induce gsdme\u2011dependent", "can induce gsdme\u2011dependent lytic cell", "induce gsdme\u2011dependent lytic cell death", "gsdme\u2011dependent lytic cell death in", "lytic cell death in tumor", "cell death in tumor targets", "death in tumor targets via", "in tumor targets via the", "tumor targets via the casp3\u2011mediated", "targets via the casp3\u2011mediated cleavage", "via the casp3\u2011mediated cleavage of", "the casp3\u2011mediated cleavage of gsdme", "cleavage of gsdme zhang", "of gsdme zhang z", "gsdme zhang z et", "zhang z et al. 2020", "z et al. 2020 .

              this", "et al. 2020 .

              this reactome", "al. 2020 .

              this reactome module", "2020 .

              this reactome module describes", ".

              this reactome module describes pyroptotic", "reactome module describes pyroptotic activities", "module describes pyroptotic activities of", "describes pyroptotic activities of gsdmd", "pyroptotic activities of gsdmd and", "activities of gsdmd and gsdme.", "of gsdmd and gsdme. while", "gsdmd and gsdme. while the", "and gsdme. while the n\u2011terminal", "gsdme. while the n\u2011terminal domains", "while the n\u2011terminal domains of", "the n\u2011terminal domains of mammalian", "n\u2011terminal domains of mammalian gsdma", "of mammalian gsdma gsdmb", "gsdma gsdmb and", "gsdmb and gsdmc also", "and gsdmc also have the", "gsdmc also have the ability", "also have the ability to", "have the ability to form", "the ability to form pores", "to form pores feng", "form pores feng s", "pores feng s et", "et al. 2018 ruan", "al. 2018 ruan j", "2018 ruan j et", "ruan j et al. 2018", "al. 2018 their", "2018 their functions", "their functions in the induction", "functions in the induction of", "in the induction of pyroptosis", "induction of pyroptosis secretion", "of pyroptosis secretion of", "pyroptosis secretion of proinflammatory", "secretion of proinflammatory cytokines or", "of proinflammatory cytokines or in", "proinflammatory cytokines or in bactericidal", "cytokines or in bactericidal activity", "or in bactericidal activity in", "in bactericidal activity in host", "bactericidal activity in host remain", "activity in host remain to", "in host remain to be", "host remain to be studied", "remain to be studied and", "to be studied and are", "be studied and are not", "studied and are not covered", "and are not covered by", "are not covered by this", "not covered by this reactome", "covered by this reactome module." ] }, { "record_id": "GLY_000594_1_1930", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013407", "r hsa", "hsa 9013407", "r hsa 9013407" ] }, { "record_id": "GLY_000594_1_1930", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhoh gtpase", "gtpase cycle", "rhoh gtpase cycle", "rhoh is", "is constitutively", "constitutively bound", "bound to", "to gtp", "gtp and", "and does", "does not", "not require", "require a", "a guanine", "guanine nucleotide", "nucleotide exchange", "exchange factor", "for activation", "li et", "et al.", "al. 2002", "2002 .", ". rhoh", "rhoh does", "not possess", "possess a", "a gtpase", "gtpase activity", "but has", "has been", "been reported", "reported to", "to bind", "bind to", "to a", "a small", "small number", "number of", "of gtpase", "gtpase activator", "activator proteins", "bagci et", "al. 2020", "which possibly", "possibly function", "function as", "as rhoh", "rhoh effectors.", "effectors. while", "while rhoh", "is not", "not found", "found in", "in the", "the gdp", "gdp bound", "bound state", "gdp dissociation", "dissociation inhibitors", "still interact", "interact with", "with rhoh", "presumably affecting", "affecting its", "its translocation", "translocation to", "to the", "the site", "site of", "of activity", "activity by", "by sequestering", "sequestering it", "it in", "the cytosol", ". similar", "similar to", "to rac2", "rhoh expression", "expression is", "is also", "also restricted", "restricted to", "to hematopoietic", "hematopoietic cells.", "cells. rhoh", "rhoh function", "function is", "is required", "required for", "for t", "t cell", "cell development", "development and", "and rhoh", "rhoh activity", "activity is", "is regulated", "regulated by", "by posttranslational", "posttranslational modifications", "modifications downstream", "downstream of", "of activated", "activated t", "cell receptor", "tcr .", ". following", "following tcr", "tcr activation", "is degraded", "degraded in", "in lysosomes", "schmidt mende", "mende et", "al. 2010", "2010 .", ". in", "in blood", "blood neutrophils", "neutrophils from", "from patients", "patients suffering", "suffering from", "from cystic", "cystic fibrosis", "fibrosis or", "or eosinophils", "eosinophils from", "patients with", "with hypereosinophilic", "hypereosinophilic syndromes", "an upregulation", "upregulation of", "of rhoh", "expression has", "been found", "daryadel et", "stoeckle et", "2016 .", "is subject", "subject to", "to mutations", "mutations and", "and translocations", "translocations in", "in lymphoma", "suzuki and", "and oda", "oda 2008", "troeger and", "and williams", "williams 2013", "2013 .", ". mutations", "mutations in", "in rhoh", "rhoh are", "are associated", "associated with", "with abnormal", "abnormal susceptibility", "susceptibility to", "to human", "human beta", "beta papillomavirus", "beta hpv", "skin infections", "which leads", "leads to", "to epidermodysplasia", "epidermodysplasia verruciformis", "a condition", "condition characterized", "characterized by", "by persistent", "persistent flat", "flat warts", "warts or", "or beta", "hpv associated", "associated skin", "skin lesions", "przybyszewska et", "al. 2017", "2017 .", "rhoh is constitutively", "is constitutively bound", "constitutively bound to", "bound to gtp", "to gtp and", "gtp and does", "and does not", "does not require", "not require a", "require a guanine", "a guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factor", "factor gef", "gef for", "activation li", "li et al.", "et al. 2002", "al. 2002 .", "2002 . rhoh", ". rhoh does", "rhoh does not", "does not possess", "not possess a", "possess a gtpase", "a gtpase activity", "activity li", "but has been", "has been reported", "been reported to", "reported to bind", "to bind to", "bind to a", "to a small", "a small number", "small number of", "number of gtpase", "of gtpase activator", "gtpase activator proteins", "proteins gaps", "bagci et al.", "et al. 2020", "which possibly function", "possibly function as", "function as rhoh", "as rhoh effectors.", "rhoh effectors. while", "effectors. while rhoh", "while rhoh is", "rhoh is not", "is not found", "not found in", "found in the", "in the gdp", "the gdp bound", "gdp bound state", "state gdp", "gdp dissociation inhibitors", "inhibitors gdis", "still interact with", "interact with rhoh", "rhoh presumably", "presumably affecting its", "affecting its translocation", "its translocation to", "translocation to the", "to the site", "the site of", "site of activity", "of activity by", "activity by sequestering", "by sequestering it", "sequestering it in", "it in the", "in the cytosol", "cytosol li", "2002 . similar", ". similar to", "similar to rac2", "rac2 rhoh", "rhoh expression is", "expression is also", "is also restricted", "also restricted to", "restricted to hematopoietic", "to hematopoietic cells.", "hematopoietic cells. rhoh", "cells. rhoh function", "rhoh function is", "function is required", "is required for", "required for t", "for t cell", "t cell development", "cell development and", "development and rhoh", "and rhoh activity", "rhoh activity is", "activity is regulated", "is regulated by", "regulated by posttranslational", "by posttranslational modifications", "posttranslational modifications downstream", "modifications downstream of", "downstream of activated", "of activated t", "activated t cell", "t cell receptor", "receptor tcr", "tcr . following", ". following tcr", "following tcr activation", "activation rhoh", "rhoh is degraded", "is degraded in", "degraded in lysosomes", "lysosomes schmidt", "schmidt mende et", "mende et al.", "et al. 2010", "al. 2010 .", "2010 . in", ". in blood", "in blood neutrophils", "blood neutrophils from", "neutrophils from patients", "from patients suffering", "patients suffering from", "suffering from cystic", "from cystic fibrosis", "cystic fibrosis or", "fibrosis or eosinophils", "or eosinophils from", "eosinophils from patients", "from patients with", "patients with hypereosinophilic", "with hypereosinophilic syndromes", "syndromes an", "an upregulation of", "upregulation of rhoh", "of rhoh expression", "rhoh expression has", "expression has been", "has been found", "found daryadel", "daryadel et al.", "al. 2009", "2009 stoeckle", "stoeckle et al.", "al. 2016", "2016 . rhoh", ". rhoh is", "rhoh is subject", "is subject to", "subject to mutations", "to mutations and", "mutations and translocations", "and translocations in", "translocations in lymphoma", "lymphoma suzuki", "suzuki and oda", "and oda 2008", "2008 troeger", "troeger and williams", "and williams 2013", "williams 2013 .", "2013 . mutations", ". mutations in", "mutations in rhoh", "in rhoh are", "rhoh are associated", "are associated with", "associated with abnormal", "with abnormal susceptibility", "abnormal susceptibility to", "susceptibility to human", "to human beta", "human beta papillomavirus", "papillomavirus beta", "hpv skin", "infections which", "which leads to", "leads to epidermodysplasia", "to epidermodysplasia verruciformis", "verruciformis a", "a condition characterized", "condition characterized by", "characterized by persistent", "by persistent flat", "persistent flat warts", "flat warts or", "warts or beta", "or beta hpv", "beta hpv associated", "hpv associated skin", "associated skin lesions", "lesions przybyszewska", "przybyszewska et al.", "et al. 2017", "al. 2017 .", "rhoh is constitutively bound", "is constitutively bound to", "constitutively bound to gtp", "bound to gtp and", "to gtp and does", "gtp and does not", "and does not require", "does not require a", "not require a guanine", "require a guanine nucleotide", "a guanine nucleotide exchange", "guanine nucleotide exchange factor", "exchange factor gef", "gef for activation", "for activation li", "activation li et", "li et al. 2002", "et al. 2002 .", "al. 2002 . rhoh", "2002 . rhoh does", ". rhoh does not", "rhoh does not possess", "does not possess a", "not possess a gtpase", "possess a gtpase activity", "gtpase activity li", "activity li et", "2002 but", "but has been reported", "has been reported to", "been reported to bind", "reported to bind to", "to bind to a", "bind to a small", "to a small number", "a small number of", "small number of gtpase", "number of gtpase activator", "of gtpase activator proteins", "activator proteins gaps", "gaps bagci", "bagci et al. 2020", "2020 which", "which possibly function as", "possibly function as rhoh", "function as rhoh effectors.", "as rhoh effectors. while", "rhoh effectors. while rhoh", "effectors. while rhoh is", "while rhoh is not", "rhoh is not found", "is not found in", "not found in the", "found in the gdp", "in the gdp bound", "the gdp bound state", "bound state gdp", "state gdp dissociation", "dissociation inhibitors gdis", "gdis still", "still interact with rhoh", "with rhoh presumably", "rhoh presumably affecting", "presumably affecting its translocation", "affecting its translocation to", "its translocation to the", "translocation to the site", "to the site of", "the site of activity", "site of activity by", "of activity by sequestering", "activity by sequestering it", "by sequestering it in", "sequestering it in the", "it in the cytosol", "the cytosol li", "cytosol li et", "al. 2002 . similar", "2002 . similar to", ". similar to rac2", "to rac2 rhoh", "rac2 rhoh expression", "rhoh expression is also", "expression is also restricted", "is also restricted to", "also restricted to hematopoietic", "restricted to hematopoietic cells.", "to hematopoietic cells. rhoh", "hematopoietic cells. rhoh function", "cells. rhoh function is", "rhoh function is required", "function is required for", "is required for t", "required for t cell", "for t cell development", "t cell development and", "cell development and rhoh", "development and rhoh activity", "and rhoh activity is", "rhoh activity is regulated", "activity is regulated by", "is regulated by posttranslational", "regulated by posttranslational modifications", "by posttranslational modifications downstream", "posttranslational modifications downstream of", "modifications downstream of activated", "downstream of activated t", "of activated t cell", "activated t cell receptor", "cell receptor tcr", "receptor tcr .", "tcr . following tcr", ". following tcr activation", "tcr activation rhoh", "activation rhoh is", "rhoh is degraded in", "is degraded in lysosomes", "in lysosomes schmidt", "lysosomes schmidt mende", "schmidt mende et al.", "mende et al. 2010", "et al. 2010 .", "al. 2010 . in", "2010 . in blood", ". in blood neutrophils", "in blood neutrophils from", "blood neutrophils from patients", "neutrophils from patients suffering", "from patients suffering from", "patients suffering from cystic", "suffering from cystic fibrosis", "from cystic fibrosis or", "cystic fibrosis or eosinophils", "fibrosis or eosinophils from", "or eosinophils from patients", "eosinophils from patients with", "from patients with hypereosinophilic", "patients with hypereosinophilic syndromes", "hypereosinophilic syndromes an", "syndromes an upregulation", "an upregulation of rhoh", "upregulation of rhoh expression", "of rhoh expression has", "rhoh expression has been", "expression has been found", "been found daryadel", "found daryadel et", "et al. 2009", "2009 stoeckle et", "et al. 2016", "al. 2016 .", "2016 . rhoh is", ". rhoh is subject", "rhoh is subject to", "is subject to mutations", "subject to mutations and", "to mutations and translocations", "mutations and translocations in", "and translocations in lymphoma", "in lymphoma suzuki", "lymphoma suzuki and", "suzuki and oda 2008", "oda 2008 troeger", "2008 troeger and", "troeger and williams 2013", "and williams 2013 .", "williams 2013 . mutations", "2013 . mutations in", ". mutations in rhoh", "mutations in rhoh are", "in rhoh are associated", "rhoh are associated with", "are associated with abnormal", "associated with abnormal susceptibility", "with abnormal susceptibility to", "abnormal susceptibility to human", "susceptibility to human beta", "to human beta papillomavirus", "beta papillomavirus beta", "papillomavirus beta hpv", "beta hpv skin", "hpv skin infections", "skin infections which", "infections which leads", "which leads to epidermodysplasia", "leads to epidermodysplasia verruciformis", "epidermodysplasia verruciformis a", "verruciformis a condition", "a condition characterized by", "condition characterized by persistent", "characterized by persistent flat", "by persistent flat warts", "persistent flat warts or", "flat warts or beta", "warts or beta hpv", "or beta hpv associated", "beta hpv associated skin", "hpv associated skin lesions", "skin lesions przybyszewska", "lesions przybyszewska et", "przybyszewska et al. 2017", "et al. 2017 .", "rhoh is constitutively bound to", "is constitutively bound to gtp", "constitutively bound to gtp and", "bound to gtp and does", "to gtp and does not", "gtp and does not require", "and does not require a", "does not require a guanine", "not require a guanine nucleotide", "require a guanine nucleotide exchange", "a guanine nucleotide exchange factor", "nucleotide exchange factor gef", "factor gef for", "for activation li et", "activation li et al.", "li et al. 2002 .", "et al. 2002 . rhoh", "al. 2002 . rhoh does", "2002 . rhoh does not", ". rhoh does not possess", "rhoh does not possess a", "does not possess a gtpase", "not possess a gtpase activity", "a gtpase activity li", "gtpase activity li et", "activity li et al.", "al. 2002 but", "2002 but has", "but has been reported to", "has been reported to bind", "been reported to bind to", "reported to bind to a", "to bind to a small", "bind to a small number", "to a small number of", "a small number of gtpase", "small number of gtpase activator", "number of gtpase activator proteins", "gtpase activator proteins gaps", "gaps bagci et", "al. 2020 which", "2020 which possibly", "which possibly function as rhoh", "possibly function as rhoh effectors.", "function as rhoh effectors. while", "as rhoh effectors. while rhoh", "rhoh effectors. while rhoh is", "effectors. while rhoh is not", "while rhoh is not found", "rhoh is not found in", "is not found in the", "not found in the gdp", "found in the gdp bound", "in the gdp bound state", "gdp bound state gdp", "bound state gdp dissociation", "state gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "gdis still interact", "interact with rhoh presumably", "with rhoh presumably affecting", "rhoh presumably affecting its", "presumably affecting its translocation to", "affecting its translocation to the", "its translocation to the site", "translocation to the site of", "to the site of activity", "the site of activity by", "site of activity by sequestering", "of activity by sequestering it", "activity by sequestering it in", "by sequestering it in the", "sequestering it in the cytosol", "in the cytosol li", "the cytosol li et", "cytosol li et al.", "et al. 2002 . similar", "al. 2002 . similar to", "2002 . similar to rac2", "similar to rac2 rhoh", "to rac2 rhoh expression", "rac2 rhoh expression is", "rhoh expression is also restricted", "expression is also restricted to", "is also restricted to hematopoietic", "also restricted to hematopoietic cells.", "restricted to hematopoietic cells. rhoh", "to hematopoietic cells. rhoh function", "hematopoietic cells. rhoh function is", "cells. rhoh function is required", "rhoh function is required for", "function is required for t", "is required for t cell", "required for t cell development", "for t cell development and", "t cell development and rhoh", "cell development and rhoh activity", "development and rhoh activity is", "and rhoh activity is regulated", "rhoh activity is regulated by", "activity is regulated by posttranslational", "is regulated by posttranslational modifications", "regulated by posttranslational modifications downstream", "by posttranslational modifications downstream of", "posttranslational modifications downstream of activated", "modifications downstream of activated t", "downstream of activated t cell", "of activated t cell receptor", "t cell receptor tcr", "cell receptor tcr .", "receptor tcr . following", "tcr . following tcr activation", "following tcr activation rhoh", "tcr activation rhoh is", "activation rhoh is degraded", "rhoh is degraded in lysosomes", "degraded in lysosomes schmidt", "in lysosomes schmidt mende", "lysosomes schmidt mende et", "schmidt mende et al. 2010", "mende et al. 2010 .", "et al. 2010 . in", "al. 2010 . in blood", "2010 . in blood neutrophils", ". in blood neutrophils from", "in blood neutrophils from patients", "blood neutrophils from patients suffering", "neutrophils from patients suffering from", "from patients suffering from cystic", "patients suffering from cystic fibrosis", "suffering from cystic fibrosis or", "from cystic fibrosis or eosinophils", "cystic fibrosis or eosinophils from", "fibrosis or eosinophils from patients", "or eosinophils from patients with", "eosinophils from patients with hypereosinophilic", "from patients with hypereosinophilic syndromes", "with hypereosinophilic syndromes an", "hypereosinophilic syndromes an upregulation", "syndromes an upregulation of", "an upregulation of rhoh expression", "upregulation of rhoh expression has", "of rhoh expression has been", "rhoh expression has been found", "has been found daryadel", "been found daryadel et", "found daryadel et al.", "daryadel et al. 2009", "al. 2009 stoeckle", "2009 stoeckle et al.", "stoeckle et al. 2016", "et al. 2016 .", "al. 2016 . rhoh", "2016 . rhoh is subject", ". rhoh is subject to", "rhoh is subject to mutations", "is subject to mutations and", "subject to mutations and translocations", "to mutations and translocations in", "mutations and translocations in lymphoma", "translocations in lymphoma suzuki", "in lymphoma suzuki and", "lymphoma suzuki and oda", "and oda 2008 troeger", "oda 2008 troeger and", "2008 troeger and williams", "troeger and williams 2013 .", "and williams 2013 . mutations", "williams 2013 . mutations in", "2013 . mutations in rhoh", ". mutations in rhoh are", "mutations in rhoh are associated", "in rhoh are associated with", "rhoh are associated with abnormal", "are associated with abnormal susceptibility", "associated with abnormal susceptibility to", "with abnormal susceptibility to human", "abnormal susceptibility to human beta", "susceptibility to human beta papillomavirus", "human beta papillomavirus beta", "beta papillomavirus beta hpv", "beta hpv skin infections", "skin infections which leads", "infections which leads to", "which leads to epidermodysplasia verruciformis", "to epidermodysplasia verruciformis a", "epidermodysplasia verruciformis a condition", "verruciformis a condition characterized", "a condition characterized by persistent", "condition characterized by persistent flat", "characterized by persistent flat warts", "by persistent flat warts or", "persistent flat warts or beta", "flat warts or beta hpv", "warts or beta hpv associated", "or beta hpv associated skin", "beta hpv associated skin lesions", "associated skin lesions przybyszewska", "skin lesions przybyszewska et", "lesions przybyszewska et al.", "przybyszewska et al. 2017 ." ] }, { "record_id": "GLY_000594_1_1931", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013418", "r hsa", "hsa 9013418", "r hsa 9013418" ] }, { "record_id": "GLY_000594_1_1931", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhobtb2 gtpase", "gtpase cycle", "rhobtb2 gtpase cycle", "rhobtb2 is", "is an", "an atypical", "atypical member", "member of", "of the", "the rho", "rho gtpase", "gtpase family", "family that", "that is", "is predicted", "predicted not", "not to", "to cycle", "cycle between", "between a", "a gtp", "gtp bound", "bound form", "form and", "and a", "a gdp", "gdp bound", "berthold et", "et al.", "al. 2008", "2008 .", ". rhobtb", "rhobtb family", "family proteins", "in contrast", "contrast to", "to other", "other rho", "rho gtpases", "possess other", "other conserved", "conserved domains", "domains in", "in addition", "addition to", "to the", "the gtpase", "gtpase domain.", "domain. the", "gtpase domain", "domain at", "at the", "the n", "n terminus", "terminus is", "is followed", "followed by", "by a", "a proline", "proline rich", "rich region", "a tandem", "tandem of", "of two", "two btb", "broad complex", "bric \u00e0", "\u00e0 brac", "a conserved", "conserved c", "c terminal", "terminal back", "btb and", "and c", "terminal kelch", "ji and", "and rivero", "rivero 2016", "2016 .", "rhobtb proteins", "proteins can", "can form", "form homo", "and heterodimers", "but the", "the role", "role of", "of dimerization", "dimerization in", "in rhobtb", "rhobtb function", "function is", "is not", "not known", ". rhobtb2", "is usually", "usually expressed", "expressed weakly", "at a", "a lower", "lower level", "level than", "than rhobtb1", ". relatively", "relatively high", "high levels", "levels of", "of rhobtb2", "rhobtb2 can", "can be", "be detected", "detected in", "in neural", "neural and", "and cardiac", "cardiac tissues", "al. 2016", "is involved", "involved in", "in cop9", "cop9 signalosome", "signalosome regulated", "regulated and", "and cul3", "cul3 dependent", "dependent protein", "protein ubiquitination", "rhobtb2 suppresses", "suppresses cellular", "cellular proliferation", "proliferation and", "and promotes", "promotes apoptosis", "rhobtb2 takes", "takes part", "part in", "in vesicle", "vesicle transport", "rhobtb2 was", "was initially", "initially discovered", "discovered as", "as the", "the gene", "gene homozygously", "homozygously deleted", "deleted in", "in breast", "breast cancer", "cancer and", "and was", "was named", "named dbc2", "cancer 2", "rhobtb2 level", "level is", "is decreased", "decreased in", "in many", "many tumor", "tumor types", "types and", "and it", "it is", "is proposed", "proposed to", "to act", "act as", "as a", "a tumor", "tumor suppressor.", "suppressor. genomic", "genomic deletions", "deletions and", "a small", "small number", "number of", "of pathogenic", "pathogenic mutations", "mutations in", "in rhobtb2", "rhobtb2 have", "have been", "been reported", "reported in", "in cancer", ". mutations", "mutations of", "rhobtb2 that", "that result", "result in", "in impaired", "impaired interaction", "interaction with", "with cul3", "cul3 have", "been found", "found to", "to cause", "cause epileptic", "epileptic encephalopathy", "belal et", "al. 2018", "2018 .", "rhobtb2 is an", "is an atypical", "an atypical member", "atypical member of", "member of the", "of the rho", "the rho gtpase", "rho gtpase family", "gtpase family that", "family that is", "that is predicted", "is predicted not", "predicted not to", "not to cycle", "to cycle between", "cycle between a", "between a gtp", "a gtp bound", "gtp bound form", "bound form and", "form and a", "and a gdp", "a gdp bound", "gdp bound form", "form berthold", "berthold et al.", "et al. 2008", "al. 2008 .", "2008 . rhobtb", ". rhobtb family", "rhobtb family proteins", "proteins in", "in contrast to", "contrast to other", "to other rho", "other rho gtpases", "gtpases possess", "possess other conserved", "other conserved domains", "conserved domains in", "domains in addition", "in addition to", "addition to the", "to the gtpase", "the gtpase domain.", "gtpase domain. the", "domain. the gtpase", "the gtpase domain", "gtpase domain at", "domain at the", "at the n", "the n terminus", "n terminus is", "terminus is followed", "is followed by", "followed by a", "by a proline", "a proline rich", "proline rich region", "region a", "a tandem of", "tandem of two", "of two btb", "btb broad", "complex tramtrack", "tramtrack bric", "bric \u00e0 brac", "brac domains", "domains and", "and a conserved", "a conserved c", "conserved c terminal", "c terminal back", "back btb", "btb and c", "and c terminal", "c terminal kelch", "kelch domain", "domain berthold", "2008 ji", "ji and rivero", "and rivero 2016", "rivero 2016 .", "2016 . rhobtb", ". rhobtb proteins", "rhobtb proteins can", "proteins can form", "can form homo", "homo and", "heterodimers but", "but the role", "the role of", "role of dimerization", "of dimerization in", "dimerization in rhobtb", "in rhobtb function", "rhobtb function is", "function is not", "is not known", "known berthold", "2016 . rhobtb2", ". rhobtb2 is", "rhobtb2 is usually", "is usually expressed", "usually expressed weakly", "weakly berthold", "at a lower", "a lower level", "lower level than", "level than rhobtb1", "rhobtb1 ji", "2016 . relatively", ". relatively high", "relatively high levels", "high levels of", "levels of rhobtb2", "of rhobtb2 can", "rhobtb2 can be", "can be detected", "be detected in", "detected in neural", "in neural and", "neural and cardiac", "and cardiac tissues", "tissues berthold", "et al. 2016", "al. 2016 .", "rhobtb2 is involved", "is involved in", "involved in cop9", "in cop9 signalosome", "cop9 signalosome regulated", "signalosome regulated and", "regulated and cul3", "and cul3 dependent", "cul3 dependent protein", "dependent protein ubiquitination", "ubiquitination berthold", ". rhobtb2 suppresses", "rhobtb2 suppresses cellular", "suppresses cellular proliferation", "cellular proliferation and", "proliferation and promotes", "and promotes apoptosis", "apoptosis ji", ". rhobtb2 takes", "rhobtb2 takes part", "takes part in", "part in vesicle", "in vesicle transport", "transport ji", ". rhobtb2 was", "rhobtb2 was initially", "was initially discovered", "initially discovered as", "discovered as the", "as the gene", "the gene homozygously", "gene homozygously deleted", "homozygously deleted in", "deleted in breast", "in breast cancer", "breast cancer and", "cancer and was", "and was named", "was named dbc2", "dbc2 deleted", "breast cancer 2", "2008 . rhobtb2", ". rhobtb2 level", "rhobtb2 level is", "level is decreased", "is decreased in", "decreased in many", "in many tumor", 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2018 .", "rhobtb2 is an atypical", "is an atypical member", "an atypical member of", "atypical member of the", "member of the rho", "of the rho gtpase", "the rho gtpase family", "rho gtpase family that", "gtpase family that is", "family that is predicted", "that is predicted not", "is predicted not to", "predicted not to cycle", "not to cycle between", "to cycle between a", "cycle between a gtp", "between a gtp bound", "a gtp bound form", "gtp bound form and", "bound form and a", "form and a gdp", "and a gdp bound", "a gdp bound form", "bound form berthold", "form berthold et", "berthold et al. 2008", "et al. 2008 .", "al. 2008 . rhobtb", "2008 . rhobtb family", ". rhobtb family proteins", "family proteins in", "proteins in contrast", "in contrast to other", "contrast to other rho", "to other rho gtpases", "rho gtpases possess", "gtpases possess other", "possess other conserved domains", "other conserved domains in", "conserved domains in addition", "domains in addition to", "in 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cardiac tissues", "cardiac tissues berthold", "tissues berthold et", "berthold et al. 2016", "et al. 2016 .", "al. 2016 . rhobtb2", ". rhobtb2 is involved", "rhobtb2 is involved in", "is involved in cop9", "involved in cop9 signalosome", "in cop9 signalosome regulated", "cop9 signalosome regulated and", "signalosome regulated and cul3", "regulated and cul3 dependent", "and cul3 dependent protein", "cul3 dependent protein ubiquitination", "protein ubiquitination berthold", "ubiquitination berthold et", "2016 . rhobtb2 suppresses", ". rhobtb2 suppresses cellular", "rhobtb2 suppresses cellular proliferation", "suppresses cellular proliferation and", "cellular proliferation and promotes", "proliferation and promotes apoptosis", "promotes apoptosis ji", "apoptosis ji and", "2016 . rhobtb2 takes", ". rhobtb2 takes part", "rhobtb2 takes part in", "takes part in vesicle", "part in vesicle transport", "vesicle transport ji", "transport ji and", "2016 . rhobtb2 was", ". rhobtb2 was initially", 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member of", "an atypical member of the", "atypical member of the rho", "member of the rho gtpase", "of the rho gtpase family", "the rho gtpase family that", "rho gtpase family that is", "gtpase family that is predicted", "family that is predicted not", "that is predicted not to", "is predicted not to cycle", "predicted not to cycle between", "not to cycle between a", "to cycle between a gtp", "cycle between a gtp bound", "between a gtp bound form", "a gtp bound form and", "gtp bound form and a", "bound form and a gdp", "form and a gdp bound", "and a gdp bound form", "gdp bound form berthold", "bound form berthold et", "form berthold et al.", "berthold et al. 2008 .", "et al. 2008 . rhobtb", "al. 2008 . rhobtb family", "2008 . rhobtb family proteins", "rhobtb family proteins in", "family proteins in contrast", "proteins in contrast to", "in contrast to other rho", "contrast to other rho gtpases", "other rho gtpases possess", "rho gtpases possess other", "gtpases possess other 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mutations", "but no mutations in rhobtb1", "no mutations in rhobtb1 have", "mutations in rhobtb1 have been", "in rhobtb1 have been detected", "rhobtb1 have been detected in", "have been detected in cancer", "detected in cancer berthold", "in cancer berthold et", "cancer berthold et al.", "rivero 2016 . rhobtb1 localizes", "2016 . rhobtb1 localizes at", ". rhobtb1 localizes at early", "rhobtb1 localizes at early endosomes", "localizes at early endosomes and", "at early endosomes and participates", "early endosomes and participates in", "endosomes and participates in the", "and participates in the architecture", "participates in the architecture of", "in the architecture of the", "the architecture of the endosomal", "architecture of the endosomal lysosomal", "of the endosomal lysosomal system", "endosomal lysosomal system long", "lysosomal system long et", "system long et al.", "long et al. 2020 ." ] }, { "record_id": "GLY_000594_1_1934", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9013425", "r hsa", "hsa 9013425", "r hsa 9013425" ] }, { "record_id": "GLY_000594_1_1934", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rhot1 gtpase", "gtpase cycle", "rhot1 gtpase cycle", "this pathway", "pathway catalogues", "catalogues guanine", "guanine nucleotide", "nucleotide exchange", "exchange factors", "and effectors", "effectors of", "of rhot1", "also known", "known as", "as miro", "miro 1", "1 .", ". rhot1", "rhot1 possesses", "possesses a", "a high", "high intrinsic", "intrinsic gtp", "gtp ase", "ase activity", "activity and", "and does", "does not", "not require", "require a", "a gtpase", "gtpase activator", "activator protein", "peters et", "et al.", "al. 2018", "2018 .", ". no", "no gdp", "gdp dissociation", "dissociation inhibitors", "have been", "been reported", "reported to", "to interact", "interact with", "with rhot1.", "rhot1. rhot1", "rhot1 is", "is a", "a 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              upregulation", "2019 .
              upregulation of", ".
              upregulation of rhot1", "of rhot1 has", "rhot1 has a", "has a neuroprotective", "a neuroprotective effect", "neuroprotective effect in", "effect in ischemic", "in ischemic stroke", "stroke wei", "wei et al.", "al. 2019 .", "this pathway catalogues guanine", "pathway catalogues guanine nucleotide", "catalogues guanine nucleotide exchange", "guanine nucleotide exchange factors", "exchange factors gefs", "gefs and effectors", "and effectors of rhot1", "of rhot1 also", "rhot1 also known", "also known as miro", "known as miro 1", "as miro 1 .", "miro 1 . rhot1", "1 . rhot1 possesses", ". rhot1 possesses a", "rhot1 possesses a high", "possesses a high intrinsic", "a high intrinsic gtp", "high intrinsic gtp ase", "intrinsic gtp ase activity", "gtp ase activity and", "ase activity and does", "activity and does not", "and does not require", "does not require a", "not require a gtpase", "require a gtpase activator", "a gtpase activator protein", "activator protein gap", "gap peters", "peters et al. 2018", "et al. 2018 .", "al. 2018 . no", "2018 . no gdp", ". no gdp dissociation", "no gdp dissociation inhibitors", "dissociation inhibitors gdis", "gdis have been", "have been reported to", "been reported to interact", "reported to interact with", "to interact with rhot1.", "interact with rhot1. rhot1", "with rhot1. rhot1 is", "rhot1. rhot1 is a", "rhot1 is a mitochondrial", "is a mitochondrial rho", "a mitochondrial rho gtpase.", "mitochondrial rho gtpase. like", "rho gtpase. like related", "gtpase. like related rhot2", "related rhot2 miro", "rhot2 miro 2", "2 rhot1", "rhot1 localizes to the", "localizes to the outer", "to the outer mitochondrial", "the outer mitochondrial membrane.", "outer mitochondrial membrane. rhot1", "mitochondrial membrane. rhot1 is", "membrane. rhot1 is implicated", "rhot1 is implicated in", "is implicated in mitochondrial", "implicated in mitochondrial movement", "in mitochondrial movement inside", "mitochondrial movement inside the", "movement inside the cells", "the cells schwarz", "cells schwarz 2013", "2013 including", "including the axonal transport", "the axonal transport of", "axonal transport of mitochondria", "transport of mitochondria in", "of mitochondria in neurons", "in neurons saxton", "neurons saxton and", "saxton and hollenbeck 2012", "hollenbeck 2012 birsa", "2012 birsa et", "birsa et al. 2013", "al. 2013 devine", "2013 devine et", "devine et al. 2016", "2016 as", "as well as mitochondrial", "well as mitochondrial fission", "as mitochondrial fission and", "mitochondrial fission and fusion", "and fusion saxton", "fusion saxton and", "and hollenbeck 2012 .", "hollenbeck 2012 . rhot1/rhot2", "2012 . rhot1/rhot2 mediated", ". rhot1/rhot2 mediated mitochondrial", "rhot1/rhot2 mediated mitochondrial turnover", "mediated mitochondrial turnover is", "mitochondrial turnover is affected", "turnover is affected in", "is affected in neurodegenerative", "affected in neurodegenerative diseases", "neurodegenerative diseases birsa", "diseases birsa et", "et al. 2016 .", "al. 2016 . rhot1", "2016 . rhot1 can", ". rhot1 can localize", "rhot1 can localize to", "can localize to peroxisomes", "localize to peroxisomes and", "to peroxisomes and regulate", "peroxisomes and regulate peroxisome", "and regulate peroxisome motility", "regulate peroxisome motility and", "peroxisome motility and fission", "and fission castro", "fission castro et", "castro et al. 2018", "al. 2018 okumoto", "2018 okumoto et", "okumoto et al. 2018", "al. 2018 covill", "2018 covill cooke", "covill cooke et al.", "cooke et al. 2020", "et al. 2020 .", "al. 2020 . rhot1", "2020 . rhot1 is", ". rhot1 is also", "rhot1 is also involved", "is also involved in", "also involved in the", "involved in the regulation", "in the regulation of", "the regulation of er", "regulation of er mitochondria", "of er mitochondria membrane", "er mitochondria membrane contact", "mitochondria membrane contact sites", "contact sites grossmann", "sites grossmann et", "grossmann et al. 2019", "al. 2019 modi", "2019 modi et", "modi et al. 2019", "et al. 2019 .
              upregulation", "al. 2019 .
              upregulation of", "2019 .
              upregulation of rhot1", ".
              upregulation of rhot1 has", "of rhot1 has a", "rhot1 has a neuroprotective", "has a neuroprotective effect", "a neuroprotective effect in", "neuroprotective effect in ischemic", "effect in ischemic stroke", "ischemic stroke wei", "stroke wei et", "wei et al. 2019", "et al. 2019 .", "this pathway catalogues guanine nucleotide", "pathway catalogues guanine nucleotide exchange", "catalogues guanine nucleotide exchange factors", "nucleotide exchange factors gefs", "factors gefs and", "gefs and effectors of", "effectors of rhot1 also", "of rhot1 also known", "rhot1 also known as", "also known as miro 1", "known as miro 1 .", "as miro 1 . rhot1", "miro 1 . rhot1 possesses", "1 . rhot1 possesses a", ". rhot1 possesses a high", "rhot1 possesses a high intrinsic", "possesses a high intrinsic gtp", "a high intrinsic gtp ase", "high intrinsic gtp ase activity", "intrinsic gtp ase activity and", "gtp ase activity and does", "ase activity and does not", "activity and does not require", "and does not require a", "does not require a gtpase", "not require a gtpase activator", "require a gtpase activator protein", "gtpase activator protein gap", "gap peters et", "peters et al. 2018 .", "et al. 2018 . no", "al. 2018 . no gdp", "2018 . no gdp dissociation", ". no gdp dissociation inhibitors", "gdp dissociation inhibitors gdis", "inhibitors gdis have", "gdis have been reported", "have been reported to interact", "been reported to interact with", "reported to interact with rhot1.", "to interact with rhot1. rhot1", "interact with rhot1. rhot1 is", "with rhot1. rhot1 is a", "rhot1. rhot1 is a mitochondrial", "rhot1 is a mitochondrial rho", "is a mitochondrial rho gtpase.", "a mitochondrial rho gtpase. like", "mitochondrial rho gtpase. like related", "rho gtpase. like related rhot2", "like related rhot2 miro", "related rhot2 miro 2", "miro 2 rhot1", "2 rhot1 localizes", "rhot1 localizes to the outer", "localizes to the outer mitochondrial", "to the outer mitochondrial membrane.", "the outer mitochondrial membrane. rhot1", "outer mitochondrial membrane. rhot1 is", "mitochondrial membrane. rhot1 is implicated", "membrane. rhot1 is implicated in", "rhot1 is implicated in mitochondrial", "is implicated in mitochondrial movement", "implicated in mitochondrial movement inside", "in mitochondrial movement inside the", "mitochondrial movement inside the cells", "inside the cells schwarz", "the cells schwarz 2013", "schwarz 2013 including", "2013 including the", "including the axonal transport of", "the axonal transport of mitochondria", "axonal transport of mitochondria in", "transport of mitochondria in neurons", "mitochondria in neurons saxton", "in neurons saxton and", "neurons saxton and hollenbeck", "and hollenbeck 2012 birsa", "hollenbeck 2012 birsa et", "2012 birsa et al.", "et al. 2013 devine", "al. 2013 devine et", "2013 devine et al.", "al. 2016 as", "2016 as well", "as well as mitochondrial fission", "well as mitochondrial fission and", "as mitochondrial fission and fusion", "fission and fusion saxton", "and fusion saxton and", "fusion saxton and hollenbeck", "saxton and hollenbeck 2012 .", "and hollenbeck 2012 . rhot1/rhot2", "hollenbeck 2012 . rhot1/rhot2 mediated", "2012 . rhot1/rhot2 mediated mitochondrial", ". rhot1/rhot2 mediated mitochondrial turnover", "rhot1/rhot2 mediated mitochondrial turnover is", "mediated mitochondrial turnover is affected", "mitochondrial turnover is affected in", "turnover is affected in neurodegenerative", "is affected in neurodegenerative diseases", "in neurodegenerative diseases birsa", "neurodegenerative diseases birsa et", "diseases birsa et al.", "devine et al. 2016 .", "et al. 2016 . rhot1", "al. 2016 . rhot1 can", "2016 . rhot1 can localize", ". rhot1 can localize to", "rhot1 can localize to peroxisomes", "can localize to peroxisomes and", "localize to peroxisomes and regulate", "to peroxisomes and regulate peroxisome", "peroxisomes and regulate peroxisome motility", "and regulate peroxisome motility and", "regulate peroxisome motility and fission", "motility and fission castro", "and fission castro et", "fission castro et al.", "et al. 2018 okumoto", "al. 2018 okumoto et", "2018 okumoto et al.", "et al. 2018 covill", "al. 2018 covill cooke", "2018 covill cooke et", "covill cooke et al. 2020", "cooke et al. 2020 .", "et al. 2020 . rhot1", "al. 2020 . rhot1 is", "2020 . rhot1 is also", ". rhot1 is also involved", "rhot1 is also involved in", "is also involved in the", "also involved in the regulation", "involved in the regulation of", "in the regulation of er", "the regulation of er mitochondria", "regulation of er mitochondria membrane", "of er mitochondria membrane contact", "er mitochondria membrane contact sites", "membrane contact sites grossmann", "contact sites grossmann et", "sites grossmann et al.", "et al. 2019 modi", "al. 2019 modi et", "2019 modi et al.", "modi et al. 2019 .
              upregulation", "et al. 2019 .
              upregulation of", "al. 2019 .
              upregulation of rhot1", "2019 .
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              upregulation of rhot1 has a", "of rhot1 has a neuroprotective", "rhot1 has a neuroprotective effect", "has a neuroprotective effect in", "a neuroprotective effect in ischemic", "neuroprotective effect in ischemic stroke", "in ischemic stroke wei", "ischemic stroke wei et", "stroke wei et al.", "wei et al. 2019 ." ] }, { "record_id": "GLY_000594_1_1935", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9690406", "r hsa", "hsa 9690406", "r hsa 9690406" ] }, { "record_id": "GLY_000594_1_1935", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "transcriptional regulation", "regulation of", "of testis", "testis differentiation", "transcriptional regulation of", "regulation of testis", "of testis differentiation", "transcriptional regulation of testis", "regulation of testis differentiation", "transcriptional regulation of testis differentiation", "in humans", "primordial germ", "germ cells", "are specified", "specified about", "about 2", "2 weeks", "weeks after", "after fertilization", "a time", "time before", "before gastrulation", "reviewed in", "in svingen", "svingen and", "and koopman", "koopman 2013", "m\u00e4kel\u00e4 et", "et al.", "al. 2019", "2019 .", ". pgcs", "pgcs are", "are initially", "initially located", "located extraembryonically", "extraembryonically and", "and then", "then migrate", "migrate to", "to colonize", "colonize the", "the gonadal", "gonadal ridges", "genital ridges", "of the", "the embryo", "embryo during", "during the", "the fifth", "fifth week", "week after", "after fertilization.", "fertilization. at", "at this", "this time", "either ovaries", "ovaries and", "and testes", "testes can", "can originate", "originate from", "from the", "gonadal ridges.", "ridges. that", "that is", "the cells", "cells of", "ridges are", "initially bipotential", "bipotential and", "and remain", "remain bipotential", "bipotential until", "until about", "about 42", "42 days", "days after", "after conception", "when transient", "transient expression", "expression of", "the sry", "sry gene", "gene located", "located on", "on the", "the y", "y chromosome", "chromosome in", "in male", "male embryos", "embryos is", "is initiated", "initiated in", "in some", "some somatic", "somatic cells", "gonadal primordium", "in sekido", "sekido and", "and lovell", "lovell badge", "badge 2013", "barrionuevo et", "al. 2013", "svingen et", "2019 .
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              the", "2019 .
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time", "a time before gastrulation", "before gastrulation reviewed", "gastrulation reviewed in", "reviewed in svingen and", "in svingen and koopman", "svingen and koopman 2013", "koopman 2013 m\u00e4kel\u00e4", "2013 m\u00e4kel\u00e4 et", "m\u00e4kel\u00e4 et al. 2019", "et al. 2019 .", "al. 2019 . pgcs", "2019 . pgcs are", ". pgcs are initially", "pgcs are initially located", "are initially located extraembryonically", "initially located extraembryonically and", "located extraembryonically and then", "extraembryonically and then migrate", "and then migrate to", "then migrate to colonize", "migrate to colonize the", "to colonize the gonadal", "colonize the gonadal ridges", "gonadal ridges genital", "ridges genital ridges", "genital ridges of", "ridges of the", "of the embryo during", "the embryo during the", "embryo during the fifth", "during the fifth week", "the fifth week after", "fifth week after fertilization.", "week after fertilization. at", "after fertilization. at this", 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on", "gene located on the", "located on the y", "on the y chromosome", "the y chromosome in", "y chromosome in male", "chromosome in male embryos", "in male embryos is", "male embryos is initiated", "embryos is initiated in", "is initiated in some", "initiated in some somatic", "in some somatic cells", "some somatic cells of", "somatic cells of the", "of the gonadal primordium", "gonadal primordium reviewed", "primordium reviewed in", "reviewed in sekido and", "in sekido and lovell", "sekido and lovell badge", "and lovell badge 2013", "badge 2013 barrionuevo", "2013 barrionuevo et", "barrionuevo et al. 2013", "al. 2013 svingen", "2013 svingen et", "svingen et al. 2013", "et al. 2019 .
              the", "al. 2019 .
              the transcription", "2019 .
              the transcription factors", ".
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"the muellerian duct of", "muellerian duct of the", "duct of the female", "of the female reproductive", "the female reproductive system.", "female reproductive system. sox9", "reproductive system. sox9 also", "system. sox9 also directly", "sox9 also directly activates", "also directly activates many", "directly activates many other", "activates many other genes", "other genes including", "genes including dhh", "including dhh rahmoun", "dhh rahmoun et", "rahmoun et al. 2017", "al. 2017 and", "2017 and inferred", "an intercellular signaling molecule", "intercellular signaling molecule required", "signaling molecule required for", "molecule required for testis", "required for testis formation.", "in humans primordial germ", "humans primordial germ cells", "primordial germ cells pgcs", "cells pgcs are", "pgcs are specified about", "are specified about 2 weeks", "specified about 2 weeks after", "about 2 weeks after fertilization", "weeks after fertilization a", "after fertilization a time", 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during the fifth week", "during the fifth week after", "the fifth week after fertilization.", "fifth week after fertilization. at", "week after fertilization. at this", "after fertilization. at this time", "at this time either", "this time either ovaries", "time either ovaries and", "either ovaries and testes can", "ovaries and testes can originate", "and testes can originate from", "testes can originate from the", "can originate from the gonadal", "originate from the gonadal ridges.", "from the gonadal ridges. that", "the gonadal ridges. that is", "ridges. that is the", "that is the cells", "is the cells of", "the cells of the gonadal", "cells of the gonadal ridges", "of the gonadal ridges are", "the gonadal ridges are initially", "gonadal ridges are initially bipotential", "ridges are initially bipotential and", "are initially bipotential and remain", "initially bipotential and remain bipotential", "bipotential and remain bipotential until", "and remain bipotential until about", "remain bipotential until about 42", "bipotential until about 42 days", "until about 42 days after", "about 42 days after conception", "days after conception when", "after conception when transient", "conception when transient expression", "when transient expression of the", "transient expression of the sry", "expression of the sry gene", "of the sry gene located", "the sry gene located on", "sry gene located on the", "gene located on the y", "located on the y chromosome", "on the y chromosome in", "the y chromosome in male", "y chromosome in male embryos", "chromosome in male embryos is", "in male embryos is initiated", "male embryos is initiated in", "embryos is initiated in some", "is initiated in some somatic", "initiated in some somatic cells", "in some somatic cells of", "some somatic cells of the", "somatic cells of the gonadal", "cells of the gonadal primordium", "the gonadal primordium reviewed", "gonadal primordium reviewed in", "primordium reviewed in sekido", "reviewed in sekido and lovell", "in sekido and lovell badge", "sekido and lovell badge 2013", "lovell badge 2013 barrionuevo", "badge 2013 barrionuevo et", "2013 barrionuevo et al.", "et al. 2013 svingen", "al. 2013 svingen et", "2013 svingen et al.", "al. 2013 m\u00e4kel\u00e4", "m\u00e4kel\u00e4 et al. 2019 .
              the", "et al. 2019 .
              the transcription", "al. 2019 .
              the transcription factors", "2019 .
              the transcription factors wt1", "transcription factors wt1 gata4", "wt1 gata4 zfpm2", "gata4 zfpm2 fog2", "fog2 and the", "and the nuclear receptor nr5a1", "nuclear receptor nr5a1 sf1", "nr5a1 sf1 activate", "sf1 activate transcription of", "transcription of sry shimamura", "of sry shimamura et", "sry shimamura et al.", "et al. 1997 hossain", "al. 1997 hossain and", "1997 hossain and saunders", "and saunders 2001 de", "saunders 2001 de santa", "2001 de santa barbara", "de santa barbara et al.", "santa barbara et al. 2001", "et al. 2001 miyamoto", "al. 2001 miyamoto et", "2001 miyamoto et al.", "et al. 2008 and", "al. 2008 and inferred", "2008 and inferred from", "and inferred from mouse homologs", "inferred from mouse homologs .", "from mouse homologs . sry", "mouse homologs . sry and", "homologs . sry and nr5a1", ". sry and nr5a1 then", "sry and nr5a1 then activate", "and nr5a1 then activate transcription", "nr5a1 then activate transcription of", "then activate transcription of sox9", "transcription of sox9 one", "of sox9 one of", "sox9 one of the", "one of the master regulators", "of the master regulators of", "the master regulators of testis", "master regulators of testis development", "regulators of testis development and", "of testis development and maintenance", "development and maintenance knower", "and maintenance knower et", "maintenance knower et al.", "et al. 2011 croft", "al. 2011 croft et", "2011 croft et al.", "et al. 2018 inferred", "al. 2018 inferred from", "2018 inferred from mouse", "from mouse homologs reviewed", "mouse homologs reviewed in", "homologs reviewed in gonen", "reviewed in gonen and lovell", "in gonen and lovell badge", "gonen and lovell badge 2019", "and lovell badge 2019 .", "lovell badge 2019 . regulation", "badge 2019 . regulation of", "2019 . regulation of genes", ". regulation of genes by", "regulation of genes by sry", "of genes by sry and", "genes by sry and then", "sry and then when", "and then when expression", "then when expression of", "when expression of sry decreases", "of sry decreases by", "sry decreases by sox9", "decreases by sox9 causes", "by sox9 causes the specification", "sox9 causes the specification of", "causes the specification of sertoli", "the specification of sertoli cells", "specification of sertoli cells that", "of sertoli cells that further", "sertoli cells that further organize", "cells that further organize formation", "that further organize formation of", "further organize formation of the", "organize formation of the testis", "formation of the testis by", "of the testis by encasing", "the testis by encasing the", "testis by encasing the primordial", "by encasing the primordial germ", "encasing the primordial germ cells", "the primordial germ cells in", "primordial germ cells in protocords", "cells in protocords which", "in protocords which then", "protocords which then form", "which then form fully developed", "then form fully developed testis", "form fully developed testis cords.
              sox9", "fully developed testis cords.
              sox9 directly", "developed testis cords.
              sox9 directly activates", "testis cords.
              sox9 directly activates its", "cords.
              sox9 directly activates its own", "directly activates its own promoter", "activates its own promoter to", "its own promoter to maintain", "own promoter to maintain sox9", "promoter to maintain sox9 expression", "to maintain sox9 expression through", "maintain sox9 expression through development", "sox9 expression through development and", "expression through development and into", "through development and into adulthood", "and into adulthood croft", "into adulthood croft et", "adulthood croft et al.", "et al. 2018 and", "al. 2018 and inferred", "2018 and inferred from", "from mouse homologs . sox9", "mouse homologs . sox9 and", "homologs . sox9 and gata4", ". sox9 and gata4 directly", "sox9 and gata4 directly activate", "and gata4 directly activate dmrt1", "directly activate dmrt1 inferred", "activate dmrt1 inferred from", "dmrt1 inferred from mouse", "mouse homologs which", "homologs which maintains", "which maintains testis specification by", "maintains testis specification by maintaining", "testis specification by maintaining expression", "specification by maintaining expression of", "by maintaining expression of sox9", "maintaining expression of sox9 and", "expression of sox9 and other", "of sox9 and other testis", "sox9 and other testis related", "and other testis related genes.", "other testis related genes. dmrt1", "testis related genes. dmrt1 also", "related genes. dmrt1 also acts", "genes. dmrt1 also acts to", "dmrt1 also acts to suppress", "also acts to suppress ovarian", "acts to suppress ovarian specification", "to suppress ovarian specification by", "suppress ovarian specification by binding", "ovarian specification by binding and", "specification by binding and repressing", "by binding and repressing foxl2", "binding and repressing foxl2 and", "and repressing foxl2 and wnt4", "repressing foxl2 and wnt4 genes", "and wnt4 genes inferred", "wnt4 genes inferred from", "genes inferred from mouse", "mouse homologs . sox9 directly", "homologs . sox9 directly activates", ". sox9 directly activates fgf9", "directly activates fgf9 inferred", "activates fgf9 inferred from", "fgf9 inferred from mouse", "homologs which acts", "which acts via fgfr2 to", "acts via fgfr2 to maintain", "via fgfr2 to maintain sox9", "fgfr2 to maintain sox9 expression", "maintain sox9 expression and", "sox9 expression and ptgds", "and ptgds inferred from", "ptgds inferred from mouse", "homologs which converts", "which converts prostaglandin h2 to", "converts prostaglandin h2 to prostaglandin", "prostaglandin h2 to prostaglandin d2", "to prostaglandin d2 a", "prostaglandin d2 a critical", "d2 a critical hormone", "a critical hormone like lipid", "critical hormone like lipid that", "hormone like lipid that recruits", "like lipid that recruits supporting", "lipid that recruits supporting cells", "that recruits supporting cells to", "recruits supporting cells to sertoli", "supporting cells to sertoli cells", "cells to sertoli cells and", "to sertoli cells and acts", "sertoli cells and acts indirectly", "cells and acts indirectly to", "and acts indirectly to maintain", "acts indirectly to maintain sox9", "indirectly to maintain sox9 expression.", "to maintain sox9 expression. sox9", "sox9 expression. sox9 nr5a1", "sox9 nr5a1 and", "nr5a1 and gata4 directly", "and gata4 directly activate amh", "directly activate amh de", "activate amh de santa", "amh de santa barbara", "santa barbara et al. 1998", "et al. 1998 and", "al. 1998 and inferred", "1998 and inferred from", "mouse homologs an", "homologs an extracellular", "an extracellular signaling molecule which", "extracellular signaling molecule which causes", "signaling molecule which causes regression", "molecule which causes regression of", "which causes regression of the", "causes regression of the muellerian", "regression of the muellerian duct", "of the muellerian duct of", "the muellerian duct of the", "muellerian duct of the female", "duct of the female reproductive", 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nucleocapsid", "of the viral nucleocapsid into", "the viral nucleocapsid into the", "viral nucleocapsid into the host", "nucleocapsid into the host cell", "into the host cell cytosol.", "the host cell cytosol. receptor", "host cell cytosol. receptor binding", "cell cytosol. receptor binding is", "cytosol. receptor binding is the", "receptor binding is the major", "binding is the major determinant", "is the major determinant of", "the major determinant of the", "major determinant of the host", "determinant of the host range", "of the host range and", "the host range and tissue", "host range and tissue tropism", "range and tissue tropism for", "and tissue tropism for a", "tissue tropism for a coronavirus.", "tropism for a coronavirus. some", "for a coronavirus. some human", "a coronavirus. some human coronaviruses", "some human coronaviruses hcovs", "coronaviruses hcovs have", "hcovs have adopted cell", "have adopted cell surface enzymes", "adopted cell surface enzymes as", "cell surface 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cysteine", "the endosomal cysteine protease cathepsin", "endosomal cysteine protease cathepsin l", "cysteine protease cathepsin l and", "protease cathepsin l and another", "cathepsin l and another trypsin", "l and another trypsin like", "and another trypsin like serine", "another trypsin like serine protease.", "trypsin like serine protease. type", "like serine protease. type ii", "serine protease. type ii transmembrane", "protease. type ii transmembrane serine", "type ii transmembrane serine proteases", "ii transmembrane serine proteases tmprss2", "transmembrane serine proteases tmprss2 and", "serine proteases tmprss2 and tmprss11d", "proteases tmprss2 and tmprss11d have", "tmprss2 and tmprss11d have also", "and tmprss11d have also been", "tmprss11d have also been implicated", "have also been implicated in", "also been implicated in the", "been implicated in the activation", "implicated in the activation of", "in the activation of s", "the activation of s protein", "activation of s protein of", "of s protein of sars", "s protein of sars cov", "protein of sars cov 2.", "of sars cov 2. host", "sars cov 2. host factors", "cov 2. host factors may", "2. host factors may play", "host factors may play additional", "factors may play additional roles", "may play additional roles in", "play additional roles in viral", "additional roles in viral entry", "in viral entry not", "viral entry not annotated", "entry not annotated here", "not annotated here . valosin", "annotated here . valosin containing", "here . valosin containing protein", "valosin containing protein vcp", "protein vcp contributes", "vcp contributes by a", "contributes by a poorly understood", "by a poorly understood mechanism", "a poorly understood mechanism to", "poorly understood mechanism to the", "understood mechanism to the release", "mechanism to the release of", "to the release of coronavirus", "the release of coronavirus from", "release of coronavirus from early", "of coronavirus from early endosomes.", "coronavirus from early endosomes. host", "from early endosomes. host factors", "early endosomes. host factors may", "endosomes. host factors may also", "host factors may also restrict", "factors may also restrict the", "may also restrict the attachment", "also restrict the attachment and", "restrict the attachment and entry", "the attachment and entry of", "attachment and entry of hcov." ] }, { "record_id": "GLY_000594_1_1937", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9694676", "r hsa", "hsa 9694676", "r hsa 9694676" ] }, { "record_id": "GLY_000594_1_1937", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translation of", "of replicase", "replicase and", "and assembly", "assembly of", "of the", "the replication", "replication transcription", "transcription complex", "translation of replicase", "of replicase and", "replicase and assembly", "and assembly of", "assembly of 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              programmed ribosomal", "assembled and anchored.

              programmed ribosomal frameshifting", "anchored.

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other ras like", "from other ras like superfamily", "other ras like superfamily members", "ras like superfamily members and", "like superfamily members and actually", "superfamily members and actually displays", "members and actually displays atpase", "and actually displays atpase activity", "displays atpase activity espinosa", "atpase activity espinosa et", "activity espinosa et al.", "espinosa et al. 2009 .", "et al. 2009 . all", "al. 2009 . all three", "2009 . all three rhobtbs", ". all three rhobtbs possess", "all three rhobtbs possess other", "three rhobtbs possess other conserved", "rhobtbs possess other conserved domains", "possess other conserved domains in", "other conserved domains in addition", "conserved domains in addition to", "domains in addition to the", "in addition to the gtpase", "addition to the gtpase domain.", "to the gtpase domain. the", "the gtpase domain. the gtpase", "gtpase domain. the gtpase domain", "domain. the gtpase domain at", "the gtpase domain at the", "gtpase domain at the n", "domain at the n terminus", "at the n terminus is", "the n terminus is followed", "n terminus is followed by", "terminus is followed by a", "is followed by a proline", "followed by a proline rich", "by a proline rich region", "proline rich region a", "rich region a tandem", "region a tandem of", "a tandem of two btb", "of two btb broad", "two btb broad complex", "complex tramtrack bric", "tramtrack bric \u00e0 brac", "bric \u00e0 brac domains", "brac domains and", "domains and a conserved", "and a conserved c terminal", "a conserved c terminal back", "c terminal back btb", "terminal back btb and", "back btb and c", "btb and c terminal kelch", "and c terminal kelch .", "c terminal kelch . unlike", "terminal kelch . unlike rhobtb1", "kelch . unlike rhobtb1 and", ". unlike rhobtb1 and rhobtb2", "rhobtb1 and rhobtb2 rhobtb3", "and rhobtb2 rhobtb3 has", "rhobtb2 rhobtb3 has a", "rhobtb3 has a caax box", "a caax box prenylation", "caax box prenylation motif", "motif domain berthold", "domain berthold et al.", "et al. 2008 ji", "al. 2008 ji and", "2008 ji and rivero", "ji and rivero 2016 .", "and rivero 2016 . rhobtb", "rivero 2016 . rhobtb proteins", "2016 . rhobtb proteins can", ". rhobtb proteins can form", "rhobtb proteins can form homo", "proteins can form homo and", "can form homo and heterodimers", "homo and heterodimers but", "and heterodimers but the", "heterodimers but the role", "but the role of dimerization", "the role of dimerization in", "role of dimerization in rhobtb", "of dimerization in rhobtb function", "dimerization in rhobtb function is", "in rhobtb function is not", "rhobtb function is not known", "is not known berthold", "not known berthold et", "known berthold et al.", "and rivero 2016 . rhobtb3", "rivero 2016 . rhobtb3 is", "2016 . rhobtb3 is ubiquitously", ". rhobtb3 is ubiquitously expressed", "is ubiquitously expressed with", "ubiquitously expressed with high", "expressed with high levels", "with high levels in placenta", "levels in placenta testis", "placenta testis pancreas", "testis pancreas adrenal", "pancreas adrenal and salivary", "adrenal and salivary glands and", "and salivary glands and neural", "salivary glands and neural and", "glands and neural and cardiac", "and neural and cardiac tissues", "and cardiac tissues berthold", "cardiac tissues berthold et", "tissues berthold et al.", "berthold et al. 2016 .", "et al. 2016 . rhobtb3", "al. 2016 . rhobtb3 is", "2016 . rhobtb3 is involved", ". rhobtb3 is involved in", "rhobtb3 is involved in cul3", "is involved in cul3 dependent", "involved in cul3 dependent protein", "in cul3 dependent protein ubiquitination", "dependent protein ubiquitination berthold", "protein ubiquitination berthold et", "ubiquitination berthold et al.", "rhobtb3 is involved in retrograde", "is involved in retrograde transport", "involved in retrograde transport from", "in retrograde transport from endosomes", "retrograde transport from endosomes to", "transport from endosomes to the", "from endosomes to the golgi", "endosomes to the golgi apparatus", "the golgi apparatus espinosa", "golgi apparatus espinosa et", "apparatus espinosa et al.", "et al. 2009 . rhobtb3", "al. 2009 . rhobtb3 participates", "2009 . rhobtb3 participates in", ". rhobtb3 participates in regulation", "rhobtb3 participates in regulation of", "participates in regulation of the", "in regulation of the cell", "regulation of the cell cycle", "of the cell cycle and", "the cell cycle and in", "cell cycle and in modulating", "cycle and in modulating the", "and in modulating the adaptive", "in modulating the adaptive response", "modulating the adaptive response to", "the adaptive response to hypoxia", "response to hypoxia ji", "to hypoxia ji and", "hypoxia ji and rivero", "rivero 2016 . rhobtb3 level", "2016 . rhobtb3 level is", ". rhobtb3 level is decreased", "rhobtb3 level is decreased in", "level is decreased in many", "is decreased in many tumor", "decreased in many tumor types", "in many tumor types and", "many tumor types and it", "tumor types and it is", "types and it is proposed", "and it is proposed to", "it is proposed to act", "is proposed to act as", "proposed to act as a", "to act as a tumor", "act as a tumor suppressor", "a tumor suppressor although", "tumor suppressor although no", "suppressor although no pathogenic", "although no pathogenic mutations have", "no pathogenic mutations have been", "pathogenic mutations have been reported", "have been reported berthold", "been reported berthold et", "reported berthold et al." ] }, { "record_id": "GLY_000594_1_1942", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9710421", "r hsa", "hsa 9710421", "r hsa 9710421" ] }, { "record_id": "GLY_000594_1_1942", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pyroptosis", "pyroptosis is", "is a", "a form", "form of", "of lytic", "lytic inflammatory", 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et", "l et al.", "et al. 2020", "al. 2020 .", "2020 . during", ". during infections", "infections the", "the excessive production", "excessive production of", "production of cytokines", "of cytokines can", "cytokines can lead", "can lead to", "lead to a", "to a cytokine", "a cytokine storm", "storm which", "which is associated", "is associated with", "associated with acute", "with acute respiratory", "acute respiratory distress", "respiratory distress syndrome", "syndrome ards", "ards and", "and systemic inflammatory", "systemic inflammatory response", "inflammatory response syndrome", "syndrome sirs", "reviewed in tisoncik", "in tisoncik jr", "tisoncik jr et", "jr et al.", "et al. 2012", "2012 karki", "karki r et", "r et al.", "2020 ragab", "ragab d et", "2020 . pyroptosis", ". pyroptosis has", "pyroptosis has a", "has a close", "a close but", "close but complicated", "but complicated relationship", "complicated relationship to", "relationship to tumorigenesis", "tumorigenesis 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              this", "2021 .

              this reactome", ".

              this reactome module", "reactome module describes", "module describes the", "describes the defective", "the defective gsdme", "defective gsdme function", "gsdme function caused", "function caused by", "caused by cancer\u2011related", "by cancer\u2011related gsdme", "cancer\u2011related gsdme mutations", "mutations zhang", "2020 . it", ". it also", "it also shows", "also shows epigenetic", "shows epigenetic inactivation", "epigenetic inactivation of", "inactivation of gsdme", "of gsdme due", "gsdme due to", "due to hypermethylation", "to hypermethylation of", "hypermethylation of the", "of the gsdme", "the gsdme promoter", "gsdme promoter region", "region akino", "akino k et", "k et al.", "et al. 2007", "2007 kim", "kim ms et", "ms et al.", "et al. 2008a", "al. 2008a b", "b croes", "croes l et", "2017 2018", "2018 ibrahim", "ibrahim j et", "2019 . aberrant", ". aberrant promoter", "aberrant promoter methylation", "promoter methylation is", "methylation is considered", "is considered to", "considered to be", "to be a", "be a hallmark", "a hallmark of", "hallmark of cancer", "cancer ehrlich", "ehrlich m et", "et al. 2002", "2002 dong", "dong y et", "y et al.", "et al. 2014", "2014 lam", "lam k et", "et al. 2016", "2016 croes", "et al. 2018", "al. 2018 .", "2018 . treatment", ". treatment with", "treatment with the", "with the dna", "the dna methyltransferase", "dna methyltransferase inhibitor", "methyltransferase inhibitor decitabine", "decitabine 5\u2011aza\u20112'\u2011deoxycytidine", "5\u2011aza\u20112'\u2011deoxycytidine or dac", "dac may", "may elevate gsdme", "elevate gsdme expression", "gsdme expression in", "expression in certain", "in certain cancer", "certain cancer cells", "cells akino", "2007 fujikane", "fujikane t et", "t et al.", "et al. 2009", "2009 wang", "wang y et", "al. 2017 .", "pyroptosis is a form", "is a form of", "a form of lytic", "form of lytic inflammatory", "of lytic inflammatory programmed", "lytic inflammatory programmed cell", "inflammatory programmed cell death", "programmed cell death that", "cell death that is", "death that is mediated", "that is mediated by", "is mediated by the", "mediated by the pore\u2011forming", "by the pore\u2011forming gasdermins", "pore\u2011forming gasdermins gsdms", "gsdms shi", "shi j et al.", "j et al. 2017", "al. 2017 to", "2017 to stimulate", "to stimulate immune responses", "stimulate immune responses through", "immune responses through the", "responses through the release", "through the release of", "the release of pro\u2011inflammatory", "release of pro\u2011inflammatory interleukin", "pro\u2011inflammatory interleukin il", "interleukin il \u20111\u03b2", "il \u20111\u03b2 il\u201118", "il\u201118 mainly in", "mainly in gsdmd mediated", "in gsdmd mediated pyroptosis", "mediated pyroptosis as", "pyroptosis as well", "as well as danger", "well as danger signals", "as danger signals such", "danger signals such as", "signals such as adenosine", "such as adenosine triphosphate", "adenosine triphosphate atp", "atp or high", "or high mobility group", "high mobility group protein", "mobility group protein b1", "protein b1 hmgb1", "hmgb1 reviewed", "reviewed in shi j", "in shi j et", "al. 2017 man", "2017 man sm", "man sm et al.", "sm et al. 2017", "al. 2017 tang", "2017 tang d", "tang d et al.", "d et al. 2019", "al. 2019 lieberman", "2019 lieberman j", "lieberman j et al.", "j et al. 2019", "et al. 2019 .", "al. 2019 . pyroptosis", "2019 . pyroptosis protects", ". pyroptosis protects the", "pyroptosis protects the host", "protects the host from", "the host from microbial", "host from microbial infection", "from microbial infection but", "microbial infection but can", "infection but can also", "but can also lead", "can also lead to", "also lead to pathological", "lead to pathological inflammation", "to pathological inflammation if", "pathological inflammation if overactivated", "inflammation if overactivated or", "if overactivated or dysregulated", "or dysregulated reviewed", "dysregulated reviewed in", "reviewed in orning p", "in orning p et", "orning p et al.", "p et al. 2019", "al. 2019 tang", "2019 tang l", "tang l et al.", "l et al. 2020", "et al. 2020 .", "al. 2020 . during", "2020 . during infections", "during infections the", "infections the excessive", "the excessive production of", "excessive production of cytokines", "production of cytokines can", "of cytokines can lead", "cytokines can lead to", "can lead to a", "lead to a cytokine", "to a cytokine storm", "cytokine storm which", "storm which is", "which is associated with", "is associated with acute", "associated with acute respiratory", "with acute respiratory distress", "acute respiratory distress syndrome", "distress syndrome ards", "ards and systemic", "and systemic inflammatory response", "systemic inflammatory response syndrome", "response syndrome sirs", "sirs reviewed", "reviewed in tisoncik jr", "in tisoncik jr et", "tisoncik jr et al.", "jr et al. 2012", 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in", "effector mechanism in antitumor", "mechanism in antitumor immunity", "antitumor immunity wang", "immunity wang q", "wang q et al.", "q et al. 2020", "al. 2020 zhou", "zhou z et", "z et al. 2020", "al. 2020 zhang", "2020 zhang z", "zhang z et al.", "2020 while", "while in other cases", "other cases as", "cases as a", "as a type of", "a type of proinflammatory", "type of proinflammatory death", "proinflammatory death pyroptosis", "death pyroptosis can", "pyroptosis can contribute to", "can contribute to the", "contribute to the formation", "to the formation of", "the formation of a", "formation of a microenvironment", "of a microenvironment suitable", "a microenvironment suitable for", "microenvironment suitable for tumor", "suitable for tumor cell", "for tumor cell growth", "cell growth reviewed", "growth reviewed in", "reviewed in xia x", "in xia x et", "xia x et al.", "x et al. 2019", "al. 2019 jiang", "2019 jiang m", "jiang m et al.", "m et al. 2020", "z et al. 2021", "et al. 2021 .

              this", "al. 2021 .

              this reactome", "2021 .

              this reactome module", ".

              this reactome module describes", "reactome module describes the", "module describes the defective", "describes the defective gsdme", "the defective gsdme function", "defective gsdme function caused", "gsdme function caused by", "function caused by cancer\u2011related", "caused by cancer\u2011related gsdme", "by cancer\u2011related gsdme mutations", "gsdme mutations zhang", "mutations zhang z", "al. 2020 . it", "2020 . it also", ". it also shows", "it also shows epigenetic", "also shows epigenetic inactivation", "shows epigenetic inactivation of", "epigenetic inactivation of gsdme", "inactivation of gsdme due", "of gsdme due to", "gsdme due to hypermethylation", "due to hypermethylation of", "to hypermethylation of the", "hypermethylation of the gsdme", "of the gsdme promoter", "the gsdme promoter region", "promoter region akino", "region akino k", "akino k et al.", "k et al. 2007", "al. 2007 kim", "2007 kim ms", "kim ms et al.", "ms et al. 2008a", "et al. 2008a b", "2008a b croes", "b croes l", "croes l et al.", "l et al. 2017", "al. 2017 2018", "2018 ibrahim j", "ibrahim j et al.", "al. 2019 . aberrant", "2019 . aberrant promoter", ". aberrant promoter methylation", "aberrant promoter methylation is", "promoter methylation is considered", "methylation is considered to", "is considered to be", "considered to be a", "to be a hallmark", "be a hallmark of", "a hallmark of cancer", "of cancer ehrlich", "cancer ehrlich m", "ehrlich m et al.", "m et al. 2002", "al. 2002 dong", "2002 dong y", "dong y et al.", "y et al. 2014", "al. 2014 lam", "2014 lam k", "lam k et al.", "k et al. 2016", "al. 2016 croes", "2016 croes l", "l et al. 2018", "et al. 2018 .", "al. 2018 . treatment", "2018 . treatment with", ". treatment with the", "treatment with the dna", "with the dna methyltransferase", "the dna methyltransferase inhibitor", "dna methyltransferase inhibitor decitabine", "inhibitor decitabine 5\u2011aza\u20112'\u2011deoxycytidine", "decitabine 5\u2011aza\u20112'\u2011deoxycytidine or", "or dac may", "dac may elevate", "may elevate gsdme expression", "elevate gsdme expression in", "gsdme expression in certain", "expression in certain cancer", "in certain cancer cells", "cancer cells akino", "cells akino k", "al. 2007 fujikane", "2007 fujikane t", "fujikane t et al.", "t et al. 2009", "al. 2009 wang", "2009 wang y", "wang y et al.", "y et al. 2017", "et al. 2017 .", "pyroptosis is a form of", "is a form of lytic", "a form of lytic inflammatory", "form of lytic inflammatory programmed", "of lytic inflammatory programmed cell", "lytic inflammatory programmed cell death", "inflammatory programmed cell death that", "programmed cell death that is", "cell death that is mediated", "death that is mediated by", "that is mediated by the", "is mediated by the pore\u2011forming", "mediated by the pore\u2011forming gasdermins", "the pore\u2011forming gasdermins gsdms", "gsdms shi j", "shi j et al. 2017", "et al. 2017 to", "al. 2017 to stimulate", "2017 to stimulate immune", "to stimulate immune responses through", "stimulate immune responses through the", "immune responses through the release", "responses through the release of", "through the release of pro\u2011inflammatory", "the release of pro\u2011inflammatory interleukin", "of pro\u2011inflammatory interleukin il", "pro\u2011inflammatory interleukin il \u20111\u03b2", "\u20111\u03b2 il\u201118 mainly", "il\u201118 mainly in gsdmd", "mainly in gsdmd mediated pyroptosis", "gsdmd mediated pyroptosis as", "mediated pyroptosis as well", "pyroptosis as well as", "as well as danger signals", "well as danger signals such", "as danger signals such as", "danger signals such as adenosine", "signals such as adenosine triphosphate", "as adenosine triphosphate atp", "triphosphate atp or", "atp or high mobility", "or high mobility group protein", "high mobility group protein b1", "group protein b1 hmgb1", "hmgb1 reviewed in", "reviewed in shi j et", "in shi j et al.", "et al. 2017 man", "al. 2017 man sm", "2017 man sm et", "man sm et al. 2017", "et al. 2017 tang", "al. 2017 tang d", "2017 tang d et", "tang d et al. 2019", "et al. 2019 lieberman", "al. 2019 lieberman j", "2019 lieberman j et", "lieberman j et al. 2019", "j et al. 2019 .", "et al. 2019 . pyroptosis", "al. 2019 . pyroptosis protects", "2019 . pyroptosis protects the", ". pyroptosis protects the host", "pyroptosis protects the host from", "protects the host from microbial", "the host from microbial infection", "host from microbial infection but", "from microbial infection but can", "microbial infection but can also", "infection but can also lead", "but can also lead to", "can also lead to pathological", "also lead to pathological inflammation", "lead to pathological inflammation if", "to pathological inflammation if overactivated", "pathological inflammation if overactivated or", "inflammation if overactivated or dysregulated", "overactivated or dysregulated reviewed", "or dysregulated reviewed in", "dysregulated reviewed in orning", "reviewed in orning p et", "in orning p et al.", "orning p et al. 2019", "et al. 2019 tang", "al. 2019 tang l", "2019 tang l et", "tang l et al. 2020", "l et al. 2020 .", "et al. 2020 . during", "al. 2020 . during infections", ". during infections the", "during infections the excessive", "infections the excessive production", "the excessive production of cytokines", "excessive production of cytokines can", "production of cytokines can lead", "of cytokines can lead to", "cytokines can lead to a", "can lead to a cytokine", "lead to a cytokine storm", "a cytokine storm which", "cytokine storm which is", "storm which is associated", "which is associated with acute", "is associated with acute respiratory", "associated with acute respiratory distress", "with acute respiratory distress syndrome", "respiratory distress syndrome ards", "syndrome ards and", "ards and systemic inflammatory", "and systemic inflammatory response syndrome", "inflammatory response syndrome sirs", "sirs reviewed in", "reviewed in tisoncik jr et", "in tisoncik jr et al.", "tisoncik jr et al. 2012", "et al. 2012 karki", "al. 2012 karki r", "2012 karki r et", "karki r et al. 2020", "et al. 2020 ragab", "al. 2020 ragab d", "2020 ragab d et", "ragab d et al. 2020", "d et al. 2020 .", "et al. 2020 . pyroptosis", "al. 2020 . pyroptosis has", "2020 . pyroptosis has a", ". pyroptosis has a close", "pyroptosis has a close but", "has a close but complicated", "a close but complicated relationship", "close but complicated relationship to", "but complicated relationship to tumorigenesis", "relationship to tumorigenesis affected", "to tumorigenesis affected by", "tumorigenesis affected by tissue", "affected by tissue type and", "by tissue type and genetic", "tissue type and genetic background.", "type and genetic background. pyroptosis", "and genetic background. pyroptosis can", "genetic background. pyroptosis can trigger", "background. pyroptosis can trigger potent", "pyroptosis can trigger potent antitumor", "can trigger potent antitumor immune", "trigger potent antitumor immune responses", "potent antitumor immune responses or", "antitumor immune responses or serve", "immune responses or serve as", "responses or serve as an", "or serve as an effector", "serve as an effector mechanism", "as an effector mechanism in", "an effector mechanism in antitumor", "effector mechanism in antitumor immunity", "in antitumor immunity wang", "antitumor immunity wang q", "immunity wang q et", "wang q et al. 2020", "et al. 2020 zhou", "2020 zhou z", "zhou z et al.", "et al. 2020 zhang", "al. 2020 zhang z", "2020 zhang z et", "zhang z et al. 2020", "al. 2020 while", "2020 while in", "in other cases as", "other cases as a", "cases as a type", "as a type of proinflammatory", "a type of proinflammatory death", "of proinflammatory death pyroptosis", "proinflammatory death pyroptosis can", "death pyroptosis can contribute", "pyroptosis can contribute to the", "can contribute to the formation", "contribute to the formation of", "to the formation of a", "the formation of a microenvironment", "formation of a microenvironment suitable", "of a microenvironment suitable for", "a microenvironment suitable for tumor", "microenvironment suitable for tumor cell", "suitable for tumor cell growth", "tumor cell growth reviewed", "cell growth reviewed in", "growth reviewed in xia", "reviewed in xia x et", "in xia x et al.", "xia x et al. 2019", "et al. 2019 jiang", "al. 2019 jiang m", "2019 jiang m et", "jiang m et al. 2020", "zhang z et al. 2021", "z et al. 2021 .

              this", "et al. 2021 .

              this reactome", "al. 2021 .

              this reactome module", "2021 .

              this reactome module describes", ".

              this reactome module describes the", "reactome module describes the defective", "module describes the defective gsdme", "describes the defective gsdme function", "the defective gsdme function caused", "defective gsdme function caused by", "gsdme function caused by cancer\u2011related", "function caused by cancer\u2011related gsdme", "caused by cancer\u2011related gsdme mutations", "cancer\u2011related gsdme mutations zhang", "gsdme mutations zhang z", "mutations zhang z et", "z et al. 2020 .", "et al. 2020 . it", "al. 2020 . it also", "2020 . it also shows", ". it also shows epigenetic", "it also shows epigenetic inactivation", "also shows epigenetic inactivation of", "shows epigenetic inactivation of gsdme", "epigenetic inactivation of gsdme due", "inactivation of gsdme due to", "of gsdme due to hypermethylation", "gsdme due to hypermethylation of", "due to hypermethylation of the", "to hypermethylation of the gsdme", "hypermethylation of the gsdme promoter", "of the gsdme promoter region", "gsdme promoter region akino", "promoter region akino k", "region akino k et", "akino k et al. 2007", "et al. 2007 kim", "al. 2007 kim ms", "2007 kim ms et", "kim ms et al. 2008a", "ms et al. 2008a b", "al. 2008a b croes", "2008a b croes l", "b croes l et", "croes l et al. 2017", "et al. 2017 2018", "2017 2018 ibrahim", "2018 ibrahim j et", "ibrahim j et al. 2019", "et al. 2019 . aberrant", "al. 2019 . aberrant promoter", "2019 . aberrant promoter methylation", ". aberrant promoter methylation is", "aberrant promoter methylation is considered", "promoter methylation is considered to", "methylation is considered to be", "is considered to be a", "considered to be a hallmark", "to be a hallmark of", "be a hallmark of cancer", "hallmark of cancer ehrlich", "of cancer ehrlich m", "cancer ehrlich m et", "ehrlich m et al. 2002", "et al. 2002 dong", "al. 2002 dong y", "2002 dong y et", "dong y et al. 2014", "et al. 2014 lam", "al. 2014 lam k", "2014 lam k et", "lam k et al. 2016", "et al. 2016 croes", "al. 2016 croes l", "2016 croes l et", "croes l et al. 2018", "l et al. 2018 .", "et al. 2018 . treatment", "al. 2018 . treatment with", "2018 . treatment with the", ". treatment with the dna", "treatment with the dna methyltransferase", "with the dna methyltransferase inhibitor", "the dna methyltransferase inhibitor decitabine", "methyltransferase inhibitor decitabine 5\u2011aza\u20112'\u2011deoxycytidine", "inhibitor decitabine 5\u2011aza\u20112'\u2011deoxycytidine or", "decitabine 5\u2011aza\u20112'\u2011deoxycytidine or dac", "5\u2011aza\u20112'\u2011deoxycytidine or dac may", "or dac may elevate", "dac may elevate gsdme", "may elevate gsdme expression in", "elevate gsdme expression in certain", "gsdme expression in certain cancer", "expression in certain cancer cells", "certain cancer cells akino", "cancer cells akino k", "cells akino k et", "et al. 2007 fujikane", "al. 2007 fujikane t", "2007 fujikane t et", "fujikane t et al. 2009", "et al. 2009 wang", "al. 2009 wang y", "2009 wang y et", "wang y et al. 2017", "y et al. 2017 ." ] }, { "record_id": "GLY_000594_1_1943", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9609690", "r hsa", "hsa 9609690", "r hsa 9609690" ] }, { "record_id": "GLY_000594_1_1943", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "hcmv early", "early events", "hcmv early events", "once in", "in the", "the cytoplasm", "cytoplasm the", "the capsid", "capsid and", "and tegument", "tegument proteins", "proteins are", "are free", "free to", "to interact", "interact with", "with host", "host proteins.", "proteins. the", "capsid travels", "travels to", "to the", "the nucleus", "where the", "the genome", "genome is", "is delivered", "delivered and", "and circularized.", "circularized. tegument", "proteins regulate", "regulate host", "host cell", "cell responses", "responses and", "and initiate", "initiate the", "the 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phosphorylation", "phosphorylation of", "of different", "different residues", "residues of", "of eml4", "eml4 could", "could reduce", "reduce or", "or increase", "increase affinity", "affinity of", "eml4 for", "for specific", "specific subpopulations", "subpopulations of", "of microtubules", "microtubules in", "in mitosis.
              a", "mitosis.
              a recurrent", "recurrent genomic", "genomic rearrangement", "reported in", "in about", "about 5%", "5% cases", "cases of", "of non", "non small", "small cell", "cell lung", "lung cancer", "fuses the", "the n", "n terminal", "terminal portion", "portion of", "eml4 with", "with the", "the c", "c terminal", "of alk", "anaplastic lymphoma", "lymphoma kinase", "resulting in", "in a", "a constitutively", "constitutively active", "active alk", "soda et", "richards et", "and nudc proteins", "nudc proteins are", "proteins are required", "are required for", "required for mitotic", "for mitotic spindle", "formation attachment", "attachment of spindle", "of spindle microtubule", "spindle microtubule ends", "microtubule ends to", "ends to kinetochores", "kinetochores and", "and alignment of", "alignment of mitotic", "of mitotic chromosome", "mitotic chromosome at", "chromosome at the", "at the metaphase", "the metaphase plate.", "metaphase plate. eml4", "plate. eml4 is", "eml4 is a", "is a wd40", "a wd40 family", "wd40 family protein", "family protein that", "protein that binds", "that binds to", "binds to interphase", "to interphase microtubules", "interphase microtubules and", "microtubules and stabilizes", "and stabilizes them", "them houtman", "houtman et al.", "et al. 2007", "2007 adib", "adib et al.", "et al. 2019", "al. 2019 .", "2019 . at", ". at mitotic", "at mitotic entry", "entry eml4", "eml4 undergoes phosphorylation", "phosphorylation pollmann", "pollmann et al.", "et al. 2006", "2006 adib", "2019 by", "by serine/threonine kinases", "serine/threonine kinases nek6", "kinases nek6 and", "nek6 and nek7", "nek7 leading", "leading to its", "to its dissociation", "its dissociation from", "dissociation from microtubules", "microtubules which", "which is necessary", "is necessary for", "necessary for the", "for the assembly", "the assembly of", "assembly of a", "of a dynamic", "a dynamic mitotic", "dynamic mitotic spindle", "spindle adib", "2019 . eml4", "eml4 through", "through its wd40", "its wd40 repeats", "repeats interacts", "interacts with nudc", "with nudc and", "nudc and recruits", "and recruits it", "recruits it to", "it to the", "to the kinetochores", "the kinetochores of", "kinetochores of the", "of the mitotic", "the mitotic spindle", "spindle chen", "chen et al.", "et al. 2015", "al. 2015 .", "2015 . it", ". it is", "it is possible", "is possible that", "possible that other", "that other mitotic", "other mitotic kinases", "kinases besides", "besides nek6 and", "nek7 also", "also phosphorylate eml4.", "phosphorylate eml4. phosphorylation", "eml4. phosphorylation of", "phosphorylation of different", "of different residues", "different residues of", "residues of eml4", "of eml4 could", "eml4 could reduce", "could reduce or", "reduce or increase", "or increase affinity", "increase affinity of", "affinity of eml4", "of eml4 for", "eml4 for specific", "for specific subpopulations", "specific subpopulations of", "subpopulations of microtubules", "of microtubules in", "microtubules in mitosis.
              a", "in mitosis.
              a recurrent", "mitosis.
              a recurrent genomic", "recurrent genomic rearrangement", "rearrangement reported", "reported in about", "in about 5%", "about 5% cases", "5% cases of", "cases of non", "of non small", "non small cell", "small cell lung", "cell lung cancer", "cancer nsclc", "nsclc fuses", "fuses the n", "the n terminal", "n terminal portion", "terminal portion of", "portion of eml4", "of eml4 with", "eml4 with the", "with the c", "the c terminal", "c terminal portion", "portion of alk", "alk anaplastic", "anaplastic lymphoma kinase", "resulting in a", "in a constitutively", "a constitutively active", "constitutively active alk", "alk soda", "soda et al.", "2007 richards", "richards et al.", "eml4 and nudc proteins", "and nudc proteins are", "nudc proteins are required", "proteins are required for", "are required for mitotic", "required for mitotic spindle", "for mitotic spindle formation", "spindle formation attachment", "formation attachment of", "attachment of spindle microtubule", "of spindle microtubule ends", "spindle microtubule ends to", "microtubule ends to kinetochores", "to kinetochores and", "kinetochores and alignment", "and alignment of mitotic", "alignment of mitotic chromosome", "of mitotic chromosome at", "mitotic chromosome at the", "chromosome at the metaphase", "at the metaphase plate.", "the metaphase plate. eml4", "metaphase plate. eml4 is", "plate. eml4 is a", "eml4 is a wd40", "is a wd40 family", "a wd40 family protein", "wd40 family protein that", "family protein that binds", "protein that binds to", "that binds to interphase", "binds to interphase microtubules", "to interphase microtubules and", "interphase microtubules and stabilizes", "microtubules and stabilizes them", "stabilizes them houtman", "them houtman et", "houtman et al. 2007", "al. 2007 adib", "2007 adib et", "adib et al. 2019", "et al. 2019 .", "al. 2019 . at", "2019 . at mitotic", ". at mitotic entry", "mitotic entry eml4", "entry eml4 undergoes", "undergoes phosphorylation pollmann", "phosphorylation pollmann et", "pollmann et al. 2006", "al. 2006 adib", "2006 adib et", "al. 2019 by", "2019 by serine/threonine", "by serine/threonine kinases nek6", "serine/threonine kinases nek6 and", "kinases nek6 and nek7", "and nek7 leading", "nek7 leading to", "leading to its dissociation", "to its dissociation from", "its dissociation from microtubules", "from microtubules which", "microtubules which is", "which is necessary for", "is necessary for the", "necessary for the assembly", "for the assembly of", "the assembly of a", "assembly of a dynamic", "of a dynamic mitotic", "a dynamic mitotic spindle", "mitotic spindle adib", "spindle adib et", "al. 2019 . eml4", ". eml4 through", "eml4 through its", "through its wd40 repeats", "wd40 repeats interacts", "repeats interacts with", "interacts with nudc and", "with nudc and recruits", "nudc and recruits it", "and recruits it to", "recruits it to the", "it to the kinetochores", "to the kinetochores of", "the kinetochores of the", "kinetochores of the mitotic", "of the mitotic spindle", "mitotic spindle chen", "spindle chen et", "chen et al. 2015", "et al. 2015 .", "al. 2015 . it", "2015 . it is", ". it is possible", "it is possible that", "is possible that other", "possible that other mitotic", "that other mitotic kinases", "mitotic kinases besides", "kinases besides nek6", "besides nek6 and nek7", "and nek7 also", "nek7 also phosphorylate", "also phosphorylate eml4. phosphorylation", "phosphorylate eml4. phosphorylation of", "eml4. phosphorylation of different", "phosphorylation of different residues", "of different residues of", "different residues of eml4", "residues of eml4 could", "of eml4 could reduce", "eml4 could reduce or", "could reduce or increase", "reduce or increase affinity", "or increase affinity of", "increase affinity of eml4", "affinity of eml4 for", "of eml4 for specific", "eml4 for specific subpopulations", "for specific subpopulations of", "specific subpopulations of microtubules", "subpopulations of microtubules in", "of microtubules in mitosis.
              a", "microtubules in mitosis.
              a recurrent", "in mitosis.
              a recurrent genomic", "mitosis.
              a recurrent genomic rearrangement", "genomic rearrangement reported", "rearrangement reported in", "reported in about 5%", "in about 5% cases", "about 5% cases of", "5% cases of non", "cases of non small", "of non small cell", "non small cell lung", "small cell lung cancer", "lung cancer nsclc", "nsclc fuses the", "fuses the n terminal", "the n terminal portion", "n terminal portion of", "terminal portion of eml4", "portion of eml4 with", "of eml4 with the", "eml4 with the c", "with the c terminal", "the c terminal portion", "c terminal portion of", "terminal portion of alk", "of alk anaplastic", "alk anaplastic lymphoma", "kinase resulting", "resulting in a constitutively", "in a constitutively active", "a constitutively active alk", "active alk soda", "alk soda et", "soda et al. 2007", "al. 2007 richards", "2007 richards et", "richards et al. 2015", "eml4 and nudc proteins are", "and nudc proteins are required", "nudc proteins are required for", "proteins are required for mitotic", "are required for mitotic spindle", "required for mitotic spindle formation", "mitotic spindle formation attachment", "spindle formation attachment of", "formation attachment of spindle", "attachment of spindle microtubule ends", "of spindle microtubule ends to", "spindle microtubule ends to kinetochores", "ends to kinetochores and", "to kinetochores and alignment", "kinetochores and alignment of", "and alignment of mitotic chromosome", "alignment of mitotic chromosome at", "of mitotic chromosome at the", "mitotic chromosome at the metaphase", "chromosome at the metaphase plate.", "at the metaphase plate. eml4", "the metaphase plate. eml4 is", "metaphase plate. eml4 is a", "plate. eml4 is a wd40", "eml4 is a wd40 family", "is a wd40 family protein", "a wd40 family protein that", "wd40 family protein that binds", "family protein that binds to", "protein that binds to interphase", "that binds to interphase microtubules", "binds to interphase microtubules and", "to interphase microtubules and stabilizes", "interphase microtubules and stabilizes them", "and stabilizes them houtman", "stabilizes them houtman et", "them houtman et al.", "et al. 2007 adib", "al. 2007 adib et", "2007 adib et al.", "adib et al. 2019 .", "et al. 2019 . at", "al. 2019 . at mitotic", "2019 . at mitotic entry", "at mitotic entry eml4", "mitotic entry eml4 undergoes", "entry eml4 undergoes phosphorylation", "eml4 undergoes phosphorylation pollmann", "undergoes phosphorylation pollmann et", "phosphorylation pollmann et al.", "et al. 2006 adib", "al. 2006 adib et", "2006 adib et al.", "et al. 2019 by", "al. 2019 by serine/threonine", "2019 by serine/threonine kinases", "by serine/threonine kinases nek6 and", "serine/threonine kinases nek6 and nek7", "nek6 and nek7 leading", "and nek7 leading to", "nek7 leading to its", "leading to its dissociation from", "to its dissociation from microtubules", "dissociation from microtubules which", "from microtubules which is", "microtubules which is necessary", "which is necessary for the", "is necessary for the assembly", "necessary for the assembly of", "for the assembly of a", "the assembly of a dynamic", "assembly of a dynamic mitotic", "of a dynamic mitotic spindle", "dynamic mitotic spindle adib", "mitotic spindle adib et", "spindle adib et al.", "et al. 2019 . eml4", "2019 . eml4 through", ". eml4 through its", "eml4 through its wd40", "its wd40 repeats interacts", "wd40 repeats interacts with", "repeats interacts with nudc", "interacts with nudc and recruits", "with nudc and recruits it", "nudc and recruits it to", "and recruits it to the", "recruits it to the kinetochores", "it to the kinetochores of", "to the kinetochores of the", "the kinetochores of the mitotic", "kinetochores of the mitotic spindle", "the mitotic spindle chen", "mitotic spindle chen et", "spindle chen et al.", "chen et al. 2015 .", "et al. 2015 . it", "al. 2015 . it is", "2015 . it is possible", ". it is possible that", "it is possible that other", "is possible that other mitotic", "possible that other mitotic kinases", "other mitotic kinases besides", "mitotic kinases besides nek6", "kinases besides nek6 and", "nek6 and nek7 also", "and nek7 also phosphorylate", "nek7 also phosphorylate eml4.", "also phosphorylate eml4. phosphorylation of", "phosphorylate eml4. phosphorylation of different", "eml4. phosphorylation of different residues", "phosphorylation of different residues of", "of different residues of eml4", "different residues of eml4 could", "residues of eml4 could reduce", "of eml4 could reduce or", "eml4 could reduce or increase", "could reduce or increase affinity", "reduce or increase affinity of", "or increase affinity of eml4", "increase affinity of eml4 for", "affinity of eml4 for specific", "of eml4 for specific subpopulations", "eml4 for specific subpopulations of", "for specific subpopulations of microtubules", "specific subpopulations of microtubules in", "subpopulations of microtubules in mitosis.
              a", "of microtubules in mitosis.
              a recurrent", "microtubules in mitosis.
              a recurrent genomic", "in mitosis.
              a recurrent genomic rearrangement", "recurrent genomic rearrangement reported", "genomic rearrangement reported in", "rearrangement reported in about", "reported in about 5% cases", "in about 5% cases of", "about 5% cases of non", "5% cases of non small", "cases of non small cell", "of non small cell lung", "non small cell lung cancer", "cell lung cancer nsclc", "cancer nsclc fuses", "nsclc fuses the n", "fuses the n terminal portion", "the n terminal portion of", "n terminal portion of eml4", "terminal portion of eml4 with", "portion of eml4 with the", "of eml4 with the c", "eml4 with the c terminal", "with the c terminal portion", "the c terminal portion of", "c terminal portion of alk", "portion of alk anaplastic", "of alk anaplastic lymphoma", "alk anaplastic lymphoma kinase", "lymphoma kinase resulting", "kinase resulting in", "resulting in a constitutively active", "in a constitutively active alk", "constitutively active alk soda", "active alk soda et", "alk soda et al.", "et al. 2007 richards", "al. 2007 richards et", "2007 richards et al.", "richards et al. 2015 ." ] }, { "record_id": "GLY_000594_1_1947", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9734195", "r hsa", "hsa 9734195", "r hsa 9734195" ] }, { "record_id": "GLY_000594_1_1947", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective aprt", "aprt disrupts", "disrupts adenine", "adenine salvage", "defective aprt disrupts", "aprt disrupts adenine", "disrupts adenine salvage", "defective aprt disrupts adenine", "aprt disrupts adenine salvage", "defective aprt disrupts adenine salvage", "normally in", "in humans", "adenine formed", "formed in", "in processes", "processes such", "such as", "as polyamine", "polyamine biosynthesis", "biosynthesis can", "can be", "be salvaged", "salvaged by", "by conversion", "conversion to", "to amp", "catalyzed by", "by aprt", "adenine phosphoribosyltransferase", "phosphoribosyltransferase .", ". in", "in the", "the absence", "absence of", "of aprt", "aprt activity", "accumulated adenine", "adenine is", "is instead", "instead converted", "converted to", "to 2", "2 8", "8 dioxo", "dioxo adenine.", "adenine. accumulation", "accumulation of", "of insoluble", "insoluble crystals", "crystals of", "of 2", "dioxo adenine", "adenine in", "the kidneys", "kidneys causes", "causes the", "the kidney", "kidney damage", "damage that", "that is", "is a", "a major", "major symptom", "symptom of", "aprt deficiency", "deficiency in", "van acker", "acker et", "et al.", "al. 1977", "boll\u00e9e et", "al. 2012", "2012 .", "normally in humans", "humans adenine", "adenine formed in", "formed in processes", "in processes such", "processes such as", "such as polyamine", "as polyamine biosynthesis", "polyamine biosynthesis can", "biosynthesis can be", "can be salvaged", "be salvaged by", "salvaged by conversion", "by conversion to", "conversion to amp", "amp catalyzed", "catalyzed by aprt", "aprt adenine", "adenine phosphoribosyltransferase .", "phosphoribosyltransferase . in", ". in the", "in the absence", "the absence of", "absence of aprt", "of aprt activity", "activity however", "however accumulated", "accumulated adenine is", "adenine is instead", "is instead converted", "instead converted to", "converted to 2", "to 2 8", "2 8 dioxo", "8 dioxo adenine.", "dioxo adenine. accumulation", "adenine. accumulation of", "accumulation of insoluble", "of insoluble crystals", "insoluble crystals of", "crystals of 2", "of 2 8", "8 dioxo adenine", "dioxo adenine in", "adenine in the", "in the kidneys", "the kidneys causes", "kidneys causes the", "causes the kidney", "the kidney damage", "kidney damage that", "damage that is", "that is a", "is a major", "a major symptom", "major symptom of", "symptom of aprt", "of aprt deficiency", "aprt deficiency in", "deficiency in humans", "humans van", "van acker et", "acker et al.", "et al. 1977", "1977 boll\u00e9e", "boll\u00e9e et al.", "et al. 2012", "al. 2012 .", "in humans adenine", "humans adenine formed", "adenine formed in processes", "formed in processes such", "in processes such as", "processes such as polyamine", "such as polyamine biosynthesis", "as polyamine biosynthesis can", "polyamine biosynthesis can be", "biosynthesis can be salvaged", "can be salvaged by", "be salvaged by conversion", "salvaged by conversion to", "by conversion to amp", "to amp catalyzed", "amp catalyzed by", "by aprt adenine", "aprt adenine phosphoribosyltransferase", "adenine phosphoribosyltransferase . in", "phosphoribosyltransferase . in the", ". in the absence", "in the absence of", "the absence of aprt", "absence of aprt activity", "aprt activity however", "however accumulated adenine", "accumulated adenine is instead", "adenine is instead converted", "is instead converted to", "instead converted to 2", "converted to 2 8", "to 2 8 dioxo", "2 8 dioxo adenine.", "8 dioxo adenine. accumulation", "dioxo adenine. accumulation of", "adenine. accumulation of insoluble", "accumulation of insoluble crystals", "of insoluble crystals of", "insoluble crystals of 2", "crystals of 2 8", "of 2 8 dioxo", "2 8 dioxo adenine", "8 dioxo adenine in", "dioxo adenine in the", "adenine in the kidneys", "in the kidneys causes", "the kidneys causes the", "kidneys causes the kidney", "causes the kidney damage", "the kidney damage that", "kidney damage that is", "damage that is a", "that is a major", "is a major symptom", "a major symptom of", "major symptom of aprt", "symptom of aprt deficiency", "of aprt deficiency in", "aprt deficiency in humans", "in humans van", "humans van acker", "van acker et al.", "acker et al. 1977", "al. 1977 boll\u00e9e", "1977 boll\u00e9e et", "boll\u00e9e et al. 2012", "et al. 2012 .", "normally in humans adenine", "in humans adenine formed", "humans adenine formed in", "adenine formed in processes such", "formed in processes such as", "in processes such as polyamine", "processes such as polyamine biosynthesis", "such as polyamine biosynthesis can", "as polyamine biosynthesis can be", "polyamine biosynthesis can be salvaged", "biosynthesis can be salvaged by", "can be salvaged by conversion", "be salvaged by conversion to", "salvaged by conversion to amp", "conversion to amp catalyzed", "to amp catalyzed by", "amp catalyzed by aprt", "catalyzed by aprt adenine", "by aprt adenine phosphoribosyltransferase", "aprt adenine phosphoribosyltransferase .", "adenine phosphoribosyltransferase . in the", "phosphoribosyltransferase . in the absence", ". in the absence of", "in the absence of aprt", "the absence of aprt activity", "of aprt activity however", "activity however accumulated", "however accumulated adenine is", "accumulated adenine is instead converted", "adenine is instead converted to", "is instead converted to 2", "instead converted to 2 8", "converted to 2 8 dioxo", "to 2 8 dioxo adenine.", "2 8 dioxo adenine. accumulation", "8 dioxo adenine. accumulation of", "dioxo adenine. accumulation of insoluble", "adenine. accumulation of insoluble crystals", "accumulation of insoluble crystals of", "of insoluble crystals of 2", "insoluble crystals of 2 8", "crystals of 2 8 dioxo", "of 2 8 dioxo adenine", "2 8 dioxo adenine in", "8 dioxo adenine in the", "dioxo adenine in the kidneys", "adenine in the kidneys causes", "in the kidneys causes the", "the kidneys causes the kidney", "kidneys causes the kidney damage", "causes the kidney damage that", "the kidney damage that is", "kidney damage that is a", "damage that is a major", "that is a major symptom", "is a major symptom of", "a major symptom of aprt", "major symptom of aprt deficiency", "symptom of aprt deficiency in", "of aprt deficiency in humans", "deficiency in humans van", "in humans van acker", "humans van acker et", "van acker et al. 1977", "et al. 1977 boll\u00e9e", "al. 1977 boll\u00e9e et", "1977 boll\u00e9e et al.", "boll\u00e9e et al. 2012 ." ] }, { "record_id": "GLY_000594_1_1948", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9734281", "r hsa", "hsa 9734281", "r hsa 9734281" ] }, { "record_id": "GLY_000594_1_1948", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective hprt1", "hprt1 disrupts", "disrupts guanine", "guanine and", "and hypoxanthine", "hypoxanthine salvage", "defective hprt1 disrupts", "hprt1 disrupts guanine", "disrupts guanine and", "guanine and hypoxanthine", "and hypoxanthine salvage", "defective hprt1 disrupts guanine", "hprt1 disrupts guanine and", "disrupts guanine and hypoxanthine", "guanine and hypoxanthine salvage", "defective hprt1 disrupts guanine and", "hprt1 disrupts guanine and hypoxanthine", "disrupts guanine and hypoxanthine salvage", "normally in", "in humans", "hypoxanthine can", "can be", "be salvaged", "salvaged by", "by conversion", "conversion to", "to gmp", "gmp and", "and imp", "catalyzed by", "by hprt1", "hypoxanthine guanine", "guanine phosphoribosyltransferase", "phosphoribosyltransferase .", ". in", "in the", "the absence", "absence of", "of hprt1", "hprt1 activity", "accumulated guanine", "hypoxanthine are", "are catabolized", "catabolized by", "by xdh", "xanthine dehydrogenase", "dehydrogenase /", "/ oxidase", "to urate", "fu &", "& jinnah", "jinnah 2012", "2012 .", "normally in humans", "humans guanine", "and hypoxanthine can", "hypoxanthine can be", "can be salvaged", "be salvaged by", "salvaged by conversion", "by conversion to", "conversion to gmp", "to gmp and", "gmp and imp", "imp catalyzed", "catalyzed by hprt1", "hprt1 hypoxanthine", "hypoxanthine guanine phosphoribosyltransferase", "guanine phosphoribosyltransferase .", "phosphoribosyltransferase . in", ". in the", "in the absence", "the absence of", "absence of hprt1", "of hprt1 activity", "activity however", "however accumulated", "accumulated guanine and", "and hypoxanthine are", "hypoxanthine are catabolized", "are catabolized by", "catabolized by xdh", "xdh xanthine", "xanthine dehydrogenase /", "dehydrogenase / oxidase", "oxidase to", "urate fu", "fu & jinnah", "& jinnah 2012", "jinnah 2012 .", "in humans guanine", "humans guanine and", "guanine and hypoxanthine can", "and hypoxanthine can be", "hypoxanthine can be salvaged", "can be salvaged by", "be salvaged by conversion", "salvaged by conversion to", "by conversion to gmp", "conversion to gmp and", "to gmp and imp", "and imp catalyzed", "imp catalyzed by", "by hprt1 hypoxanthine", "hprt1 hypoxanthine guanine", "hypoxanthine guanine phosphoribosyltransferase .", "guanine phosphoribosyltransferase . in", "phosphoribosyltransferase . in the", ". in the absence", "in the absence of", "the absence of hprt1", "absence of hprt1 activity", "hprt1 activity however", "however accumulated guanine", "accumulated guanine and hypoxanthine", "guanine and hypoxanthine are", "and hypoxanthine are catabolized", "hypoxanthine are catabolized by", "are catabolized by xdh", "by xdh xanthine", "xdh xanthine dehydrogenase", "xanthine dehydrogenase / oxidase", "/ oxidase to", "oxidase to urate", "to urate fu", "urate fu &", "fu & jinnah 2012", "& jinnah 2012 .", "normally in humans guanine", "in humans guanine and", "humans guanine and hypoxanthine", "guanine and hypoxanthine can be", "and hypoxanthine can be salvaged", "hypoxanthine can be salvaged by", "can be salvaged by conversion", "be salvaged by conversion to", "salvaged by conversion to gmp", "by conversion to gmp and", "conversion to gmp and imp", "gmp and imp catalyzed", "and imp catalyzed by", "imp catalyzed by hprt1", "catalyzed by hprt1 hypoxanthine", "by hprt1 hypoxanthine guanine", "hprt1 hypoxanthine guanine phosphoribosyltransferase", "hypoxanthine guanine phosphoribosyltransferase . in", "guanine phosphoribosyltransferase . in the", "phosphoribosyltransferase . in the absence", ". in the absence of", "in the absence of hprt1", "the absence of hprt1 activity", "of hprt1 activity however", "activity however accumulated", "however accumulated guanine and", "accumulated guanine and hypoxanthine are", "guanine and hypoxanthine are catabolized", "and hypoxanthine are catabolized by", "hypoxanthine are catabolized by xdh", "catabolized by xdh xanthine", "by xdh xanthine dehydrogenase", "xdh xanthine dehydrogenase /", "dehydrogenase / oxidase to", "/ oxidase to urate", "to urate fu &", "urate fu & jinnah", "fu & jinnah 2012 ." ] }, { "record_id": "GLY_000594_1_1949", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9734735", "r hsa", "hsa 9734735", "r hsa 9734735" ] }, { "record_id": "GLY_000594_1_1949", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective ada", "ada disrupts", "deoxy adenosine", "adenosine deamination", "defective ada disrupts", "disrupts deoxy", "deoxy adenosine deamination", "ada disrupts deoxy", "disrupts deoxy adenosine", "defective ada disrupts deoxy", "ada disrupts deoxy adenosine", "disrupts deoxy adenosine deamination", "normally in", "in humans", "adenosine and", "and deoxyadenosine", "deoxyadenosine can", "can be", "be deaminated", "deaminated to", "to inosine", "inosine and", "and deoxyinosine", "catalyzed by", "by ada", "adenosine deaminase", "deaminase .", ". in", "in the", "the absence", "absence of", "of ada", "ada activity", "accumulated nucleosides", "nucleosides disrupt", "disrupt lymphoid", "lymphoid cell", "cell function", "leading to", "to severe", "severe combined", "combined immunodeficiency", "hirschhorn et", "et al.", "al. 1989", "1990 .", "normally in humans", "humans adenosine", "adenosine and deoxyadenosine", "and deoxyadenosine can", "deoxyadenosine can be", "can be deaminated", "be deaminated to", "deaminated to inosine", "to inosine and", "inosine and deoxyinosine", "deoxyinosine catalyzed", "catalyzed by ada", "ada adenosine", "adenosine deaminase .", "deaminase . in", ". in the", "in the absence", "the absence of", "absence of ada", "of ada activity", "activity however", "however accumulated", "accumulated nucleosides disrupt", "nucleosides disrupt lymphoid", "disrupt lymphoid cell", "lymphoid cell function", "function leading", "leading to severe", "to severe combined", "severe combined immunodeficiency", "immunodeficiency hirschhorn", "hirschhorn et al.", "et al. 1989", "1989 1990", "in humans adenosine", "humans adenosine and", "adenosine and deoxyadenosine can", "and deoxyadenosine can be", "deoxyadenosine can be deaminated", "can be deaminated to", "be deaminated to inosine", "deaminated to inosine and", "to inosine and deoxyinosine", "and deoxyinosine catalyzed", "deoxyinosine catalyzed by", "by ada adenosine", "ada adenosine deaminase", "adenosine deaminase . in", "deaminase . in the", ". in the absence", "in the absence of", "the absence of ada", "absence of ada activity", "ada activity however", "however accumulated nucleosides", "accumulated nucleosides disrupt lymphoid", "nucleosides disrupt lymphoid cell", "disrupt lymphoid cell function", "cell function leading", "function leading to", "leading to severe combined", "to severe combined immunodeficiency", "combined immunodeficiency hirschhorn", "immunodeficiency hirschhorn et", "hirschhorn et al. 1989", "al. 1989 1990", "1989 1990 .", "normally in humans adenosine", "in humans adenosine and", "humans adenosine and deoxyadenosine", "adenosine and deoxyadenosine can be", "and deoxyadenosine can be deaminated", "deoxyadenosine can be deaminated to", "can be deaminated to inosine", "be deaminated to inosine and", "deaminated to inosine and deoxyinosine", "inosine and deoxyinosine catalyzed", "and deoxyinosine catalyzed by", "deoxyinosine catalyzed by ada", "catalyzed by ada adenosine", "by ada adenosine deaminase", "ada adenosine deaminase .", "adenosine deaminase . in the", "deaminase . in the absence", ". in the absence of", "in the absence of ada", "the absence of ada activity", "of ada activity however", "activity however accumulated", "however accumulated nucleosides disrupt", "accumulated nucleosides disrupt lymphoid cell", "nucleosides disrupt lymphoid cell function", "lymphoid cell function leading", "cell function leading to", "function leading to severe", "leading to severe combined immunodeficiency", "severe combined immunodeficiency hirschhorn", "combined immunodeficiency hirschhorn et", "immunodeficiency hirschhorn et al.", "et al. 1989 1990", "al. 1989 1990 ." ] }, { "record_id": "GLY_000594_1_1950", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9735763", "r hsa", "hsa 9735763", "r hsa 9735763" ] }, { "record_id": "GLY_000594_1_1950", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective pnp", "pnp disrupts", "disrupts phosphorolysis", "phosphorolysis of", "deoxy guanosine", "guanosine and", "deoxy inosine", 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"cardiovascular disease.", "disease. statins", "statins inhibit", "inhibit the", "the enzyme", "enzyme hydroxymethylglutaryl", "hydroxymethylglutaryl coenzyme", "coenzyme a", "a reductase", "which catalyzes", "catalyzes the", "the critical", "critical step", "step in", "in cholesterol", "cholesterol biosynthesis", "biosynthesis of", "of hmg", "hmg coa", "coa conversion", "conversion to", "to mevalonic", "mevalonic acid.", "acid. statins", "statins are", "are the", "the most", "most commonly", "commonly prescribed", "prescribed medication", "medication for", "for treating", "treating abnormal", "abnormal lipid", "malhotra &", "& goa", "goa 2001", "2001 .", ". atv", "atv and", "and its", "its hydroxy", "hydroxy metabolites", "metabolites collectively", "collectively inhibit", "inhibit hmgcr", "hmgcr to", "to reduce", "reduce circulating", "circulating low", "low density", "density lipoprotein", "lipoprotein cholesterol.", "cholesterol.

              atv", "

              atv is", "is transported", "transported in", "the blood", "blood almost", "almost exclusively", "exclusively bound", "bound to", "to plasma", "plasma proteins", "lennernas 2003", "is subject", "subject to", "to pre\u2011systemic", "pre\u2011systemic clearance", "clearance at", "at the", "the gastrointestinal", "gastrointestinal tract", "tract and", "and to", "to first\u2011pass", "first\u2011pass hepatic", "hepatic clearance", "which explains", "explains its", "its low", "low systemic", "systemic bioavailability", "garcia et", "et al.", "al. 2003", "2003 .", ". organic", "organic anion", "anion transporters", "transporters oatp1b1", "oatp1b3 and", "and oatp2b1", "encoded by", "by slco1b1", "and slco2b1", "are expressed", "expressed on", "on the", "the sinusoidal", "sinusoidal membrane", "membrane of", "of hepatocytes", "hepatocytes and", "and can", "can facilitate", "facilitate the", "liver uptake", "uptake of", "of drugs", "drugs such", "such as", "as atv", "kalliokoski &", "& niemi", "niemi 2009", "2009 .

              in", ".

              in hepatocytes", "to a", "a lesser", "lesser extent", "the gi", "gi tract", "atv can", "can be", "be hydroxylated", "hydroxylated by", "by cytochrome", "cytochrome p450", "p450 3a4", "to hydroxy", "or undergo", "undergo lactonization", "lactonization via", "via an", "an unstable", "unstable acyl", "acyl glucuronide", "glucuronide intermediate", "intermediate to", "to atv", "atv lactone", "mediated by", "by ugt1a3", "ugt1a3 and", "and 1a1.", "1a1. atvl", "atvl may", "may also", "also be", "by cyp3a4", "cyp3a4 to", "to hydroxylactone", "hydroxylactone metabolites.", "metabolites. the", "the lactone", "lactone metabolites", "metabolites are", "are inactive", "inactive against", "against hmgcr", "but can", "be hydrolyzed", "hydrolyzed via", "via paraoxonases", "to their", "their corresponding", "corresponding hydroxy", "hydroxy acids", "which are", "are active", "active against", "against hmgcr.", "hmgcr. elimination", "elimination of", "of atv", "its metabolites", "metabolites is", "is principally", "principally biliary", "biliary with", "with apparently", "apparently no", "no significant", "significant enterohepatic", "enterohepatic recirculation.", "recirculation. half", "half life", "is approximately", "approximately 14", "14 h", "h for", "for atorvastatin", "atorvastatin and", "and 20\u201330", "20\u201330 h", "for its", "schachter 2005", "2005 .", "atorvastatin atv", "atv brand", "brand name lipitor", "is a lipid", "a lipid lowering", "lipid lowering drug", "lowering drug of", "drug of the", "of the statin", "the statin class", "statin class of", "class of medications.", "of medications. it", "medications. it inhibits", "it inhibits the", "inhibits the endogenous", "the endogenous production", "endogenous production of", "production of cholesterol", "of cholesterol in", "cholesterol in the", "in the liver", "liver thereby", "thereby lowering abnormally", "lowering abnormally high", "abnormally high cholesterol", "high cholesterol and", "cholesterol and lipid", "and lipid levels", "levels and", "and ultimately reducing", "ultimately reducing the", "reducing the risk", "the risk of", "risk of cardiovascular", "of cardiovascular disease.", "cardiovascular disease. statins", "disease. statins inhibit", "statins inhibit the", "inhibit the enzyme", "the enzyme hydroxymethylglutaryl", "enzyme hydroxymethylglutaryl coenzyme", "hydroxymethylglutaryl coenzyme a", "coenzyme a reductase", "reductase hmgcr", "which catalyzes the", "catalyzes the critical", "the critical step", "critical step in", "step in cholesterol", "in cholesterol biosynthesis", "cholesterol biosynthesis of", "biosynthesis of hmg", "of hmg coa", "hmg coa conversion", "coa conversion to", "conversion to mevalonic", "to mevalonic acid.", "mevalonic acid. statins", "acid. statins are", "statins are the", "are the most", "the most commonly", "most commonly prescribed", "commonly prescribed medication", "prescribed medication for", "medication for treating", "for treating abnormal", "treating abnormal lipid", "abnormal lipid levels", "levels malhotra", "malhotra & goa", "& goa 2001", "goa 2001 .", "2001 . atv", ". atv and", "atv and its", "and its hydroxy", "its hydroxy metabolites", "hydroxy metabolites collectively", "metabolites collectively inhibit", "collectively inhibit hmgcr", "inhibit hmgcr to", "hmgcr to reduce", "to reduce circulating", "reduce circulating low", "circulating low density", "low density lipoprotein", "density lipoprotein cholesterol.", "lipoprotein cholesterol.

              atv", "cholesterol.

              atv is", "

              atv is transported", "is transported in", "transported in the", "in the blood", "the blood almost", "blood almost exclusively", "almost exclusively bound", "exclusively bound to", "bound to plasma", "to plasma proteins", "proteins >98%", "and is", "is subject to", "subject to pre\u2011systemic", "to pre\u2011systemic clearance", "pre\u2011systemic clearance at", "clearance at the", "at the gastrointestinal", "the gastrointestinal tract", "gastrointestinal tract and", "tract and to", "and to first\u2011pass", "to first\u2011pass hepatic", "first\u2011pass hepatic clearance", "clearance which", "which explains its", "explains its low", "its low systemic", "low systemic bioavailability", "bioavailability ~12%", "garcia et al.", "et al. 2003", "al. 2003 .", "2003 . organic", ". organic anion", "organic anion transporters", "anion transporters oatp1b1", "oatp1b1 oatp1b3", "oatp1b3 and oatp2b1", "oatp2b1 encoded", "encoded by slco1b1", "slco1b1 slco1b3", "slco1b3 and", "slco2b1 respectively", "respectively are", "are expressed on", "expressed on the", "on the sinusoidal", "the sinusoidal membrane", "sinusoidal membrane of", "membrane of hepatocytes", "of hepatocytes and", "hepatocytes and can", "and can facilitate", "can facilitate the", "facilitate the liver", "the liver uptake", "liver uptake of", "uptake of drugs", "of drugs such", "drugs such as", "such as atv", "atv kalliokoski", "kalliokoski & niemi", "& niemi 2009", "niemi 2009 .

              in", "2009 .

              in hepatocytes", "and to a", "to a lesser", "a lesser extent", "extent the", "the gi tract", "atv can be", "can be hydroxylated", "be hydroxylated by", "hydroxylated by cytochrome", "by cytochrome p450", "cytochrome p450 3a4", "3a4 cyp3a4", "to hydroxy metabolites", "metabolites or", "or undergo lactonization", "undergo lactonization via", "lactonization via an", "via an unstable", "an unstable acyl", "unstable acyl glucuronide", "acyl glucuronide intermediate", "glucuronide intermediate to", "intermediate to atv", "to atv lactone", "lactone atvl", "atvl mediated", "mediated by ugt1a3", "by ugt1a3 and", "ugt1a3 and 1a1.", "and 1a1. atvl", "1a1. atvl may", "atvl may also", "may also be", "also be hydroxylated", "hydroxylated by cyp3a4", "by cyp3a4 to", "cyp3a4 to hydroxylactone", "to hydroxylactone metabolites.", "hydroxylactone metabolites. the", "metabolites. the lactone", "the lactone metabolites", "lactone metabolites are", "metabolites are inactive", "are inactive against", "inactive against hmgcr", "hmgcr but", "but can be", "can be hydrolyzed", "be hydrolyzed via", "hydrolyzed via paraoxonases", "paraoxonases pons", "pons to", "to their corresponding", "their corresponding hydroxy", "corresponding hydroxy acids", "acids which", "which are active", "are active against", "active against hmgcr.", "against hmgcr. elimination", "hmgcr. elimination of", "elimination of atv", "of atv and", "and its metabolites", "its metabolites is", "metabolites is principally", "is principally biliary", "principally biliary with", "biliary with apparently", "with apparently no", "apparently no significant", "no significant enterohepatic", "significant enterohepatic recirculation.", "enterohepatic recirculation. half", "recirculation. half life", "life t1/2", "t1/2 is", "is approximately 14", "approximately 14 h", "14 h for", "h for atorvastatin", "for atorvastatin and", "atorvastatin and 20\u201330", "and 20\u201330 h", "20\u201330 h for", "h for its", "for its metabolites", "metabolites schachter", "schachter 2005 .", "atv brand name", "lipitor is", "is a lipid lowering", "a lipid lowering drug", "lipid lowering drug of", "lowering drug of the", "drug of the statin", "of the statin class", "the statin class of", "statin class of medications.", "class of medications. it", "of medications. it inhibits", "medications. it inhibits the", "it inhibits the endogenous", "inhibits the endogenous production", "the endogenous production of", "endogenous production of cholesterol", "production of cholesterol in", "of cholesterol in the", "cholesterol in the liver", "the liver thereby", "liver thereby lowering", "thereby lowering abnormally high", "lowering abnormally high cholesterol", "abnormally high cholesterol and", "high cholesterol and lipid", "cholesterol and lipid levels", "lipid levels and", "levels and ultimately", "and ultimately reducing the", "ultimately reducing the risk", "reducing the risk of", "the risk of cardiovascular", "risk of cardiovascular disease.", "of cardiovascular disease. statins", "cardiovascular disease. statins inhibit", "disease. statins inhibit the", "statins inhibit the enzyme", "inhibit the enzyme hydroxymethylglutaryl", "the enzyme hydroxymethylglutaryl coenzyme", "enzyme hydroxymethylglutaryl coenzyme a", "hydroxymethylglutaryl coenzyme a reductase", "a reductase hmgcr", "which catalyzes the critical", "catalyzes the critical step", "the critical step in", "critical step in cholesterol", "step in cholesterol biosynthesis", "in cholesterol biosynthesis of", "cholesterol biosynthesis of hmg", "biosynthesis of hmg coa", "of hmg coa conversion", "hmg coa conversion to", "coa conversion to mevalonic", "conversion to mevalonic acid.", "to mevalonic acid. statins", "mevalonic acid. statins are", "acid. statins are the", "statins are the most", "are the most commonly", "the most commonly prescribed", "most commonly prescribed medication", "commonly prescribed medication for", "prescribed medication for treating", "medication for treating abnormal", "for treating abnormal lipid", "treating abnormal lipid levels", "lipid levels malhotra", "levels malhotra &", "malhotra & goa 2001", "& goa 2001 .", "goa 2001 . atv", "2001 . atv and", ". atv and its", "atv and its hydroxy", "and its hydroxy metabolites", "its hydroxy metabolites collectively", "hydroxy metabolites collectively inhibit", "metabolites collectively inhibit hmgcr", "collectively inhibit hmgcr to", "inhibit hmgcr to reduce", "hmgcr to reduce circulating", "to reduce circulating low", "reduce circulating low density", "circulating low density lipoprotein", "low density lipoprotein cholesterol.", "density lipoprotein cholesterol.

              atv", "lipoprotein cholesterol.

              atv is", "cholesterol.

              atv is transported", "

              atv is transported in", "is transported in the", "transported in the blood", "in the blood almost", "the blood almost exclusively", "blood almost exclusively bound", "almost exclusively bound to", "exclusively bound to plasma", "bound to plasma proteins", "plasma proteins >98%", ">98% lennernas", "2003 and", "and is subject", "is subject to pre\u2011systemic", "subject to pre\u2011systemic clearance", "to pre\u2011systemic clearance at", "pre\u2011systemic clearance at the", "clearance at the gastrointestinal", "at the gastrointestinal tract", "the gastrointestinal tract and", "gastrointestinal tract and to", "tract and to first\u2011pass", "and to first\u2011pass hepatic", "to first\u2011pass hepatic clearance", "hepatic clearance which", "clearance which explains", "which explains its low", "explains its low systemic", "its low systemic bioavailability", "systemic bioavailability ~12%", "~12% garcia", "garcia et al. 2003", "et al. 2003 .", "al. 2003 . organic", "2003 . organic anion", ". organic anion transporters", "organic anion transporters oatp1b1", "transporters oatp1b1 oatp1b3", "oatp1b1 oatp1b3 and", "and oatp2b1 encoded", "oatp2b1 encoded by", "by slco1b1 slco1b3", "slco1b3 and slco2b1", "and slco2b1 respectively", "respectively are expressed", "are expressed on the", "expressed on the sinusoidal", "on the sinusoidal membrane", "the sinusoidal membrane of", "sinusoidal membrane of hepatocytes", "membrane of hepatocytes and", "of hepatocytes and can", "hepatocytes and can facilitate", "and can facilitate the", "can facilitate the liver", "facilitate the liver uptake", "the liver uptake of", "liver uptake of drugs", "uptake of drugs such", "of drugs such as", "drugs such as atv", "as atv kalliokoski", "atv kalliokoski &", "kalliokoski & niemi 2009", "& niemi 2009 .

              in", "niemi 2009 .

              in hepatocytes", ".

              in hepatocytes and", "hepatocytes and to", "and to a lesser", "to a lesser extent", "lesser extent the", "extent the gi", "tract atv", "atv can be hydroxylated", "can be hydroxylated by", "be hydroxylated by cytochrome", "hydroxylated by cytochrome p450", "by cytochrome p450 3a4", "p450 3a4 cyp3a4", "cyp3a4 to hydroxy", "hydroxy metabolites or", "metabolites or undergo", "or undergo lactonization via", "undergo lactonization via an", "lactonization via an unstable", "via an unstable acyl", "an unstable acyl glucuronide", "unstable acyl glucuronide intermediate", "acyl glucuronide intermediate to", "glucuronide intermediate to atv", "intermediate to atv lactone", "atv lactone atvl", "atvl mediated by", "mediated by ugt1a3 and", "by ugt1a3 and 1a1.", "ugt1a3 and 1a1. atvl", "and 1a1. atvl may", "1a1. atvl may also", "atvl may also be", "may also be hydroxylated", "also be hydroxylated by", "be hydroxylated by cyp3a4", "hydroxylated by cyp3a4 to", "by cyp3a4 to hydroxylactone", "cyp3a4 to hydroxylactone metabolites.", "to hydroxylactone metabolites. the", "hydroxylactone metabolites. the lactone", "metabolites. the lactone metabolites", "the lactone metabolites are", "lactone metabolites are inactive", "metabolites are inactive against", "are inactive against hmgcr", "against hmgcr but", "hmgcr but can", "but can be hydrolyzed", "can be hydrolyzed via", "be hydrolyzed via paraoxonases", "via paraoxonases pons", "pons to their", "to their corresponding hydroxy", "their corresponding hydroxy acids", "hydroxy acids which", "acids which are", "which are active against", "are active against hmgcr.", "active against hmgcr. elimination", "against hmgcr. elimination of", "hmgcr. elimination of atv", "elimination of atv and", "of atv and its", "atv and its metabolites", "and its metabolites is", "its metabolites is principally", "metabolites is principally biliary", "is principally biliary with", "principally biliary with apparently", "biliary with apparently no", "with apparently no significant", "apparently no significant enterohepatic", "no significant enterohepatic recirculation.", "significant enterohepatic recirculation. half", "enterohepatic recirculation. half life", "half life t1/2", "t1/2 is approximately", "is approximately 14 h", "approximately 14 h for", "14 h for atorvastatin", "h for atorvastatin and", "for atorvastatin and 20\u201330", "atorvastatin and 20\u201330 h", "and 20\u201330 h for", "20\u201330 h for its", "h for its metabolites", "its metabolites schachter", "metabolites schachter 2005", "atorvastatin atv brand", "atv brand name lipitor", "name lipitor is", "lipitor is a", "is a lipid lowering drug", "a lipid lowering drug of", "lipid lowering drug of the", "lowering drug of the statin", "drug of the statin class", "of the statin class of", "the statin class of medications.", "statin class of medications. it", "class of medications. it inhibits", "of medications. it inhibits the", "medications. it inhibits the endogenous", "it inhibits the endogenous production", "inhibits the endogenous production of", "the endogenous production of cholesterol", "endogenous production of cholesterol in", "production of cholesterol in the", "of cholesterol in the liver", "in the liver thereby", "the liver thereby lowering", "liver thereby lowering abnormally", "thereby lowering abnormally high cholesterol", "lowering abnormally high cholesterol and", "abnormally high cholesterol and lipid", "high cholesterol and lipid levels", "and lipid levels and", "lipid levels and ultimately", "levels and ultimately reducing", "and ultimately reducing the risk", "ultimately reducing the risk of", "reducing the risk of cardiovascular", "the risk of cardiovascular disease.", "risk of cardiovascular disease. statins", "of cardiovascular disease. statins inhibit", "cardiovascular disease. statins inhibit the", "disease. statins inhibit the enzyme", "statins inhibit the enzyme hydroxymethylglutaryl", "inhibit the enzyme hydroxymethylglutaryl coenzyme", "the enzyme hydroxymethylglutaryl coenzyme a", "enzyme hydroxymethylglutaryl coenzyme a reductase", "coenzyme a reductase hmgcr", "hmgcr which", "which catalyzes the critical step", "catalyzes the critical step in", "the critical step in cholesterol", "critical step in cholesterol biosynthesis", "step in cholesterol biosynthesis of", "in cholesterol biosynthesis of hmg", "cholesterol biosynthesis of hmg coa", "biosynthesis of hmg coa conversion", "of hmg coa conversion to", "hmg coa conversion to mevalonic", "coa conversion to mevalonic acid.", "conversion to mevalonic acid. statins", "to mevalonic acid. statins are", "mevalonic acid. statins are the", "acid. statins are the most", "statins are the most commonly", "are the most commonly prescribed", "the most commonly prescribed medication", "most commonly prescribed medication for", "commonly prescribed medication for treating", "prescribed medication for treating abnormal", "medication for treating abnormal lipid", "for treating abnormal lipid levels", "abnormal lipid levels malhotra", "lipid levels malhotra &", "levels malhotra & goa", "malhotra & goa 2001 .", "& goa 2001 . atv", "goa 2001 . atv and", "2001 . atv and its", ". atv and its hydroxy", "atv and its hydroxy metabolites", "and its hydroxy metabolites collectively", "its hydroxy metabolites collectively inhibit", "hydroxy metabolites collectively inhibit hmgcr", "metabolites collectively inhibit hmgcr to", "collectively inhibit hmgcr to reduce", "inhibit hmgcr to reduce circulating", "hmgcr to reduce circulating low", "to reduce circulating low density", "reduce circulating low density lipoprotein", "circulating low density lipoprotein cholesterol.", "low density lipoprotein cholesterol.

              atv", "density lipoprotein cholesterol.

              atv is", "lipoprotein cholesterol.

              atv is transported", "cholesterol.

              atv is transported in", "

              atv is transported in the", "is transported in the blood", "transported in the blood almost", "in the blood almost exclusively", "the blood almost exclusively bound", "blood almost exclusively bound to", "almost exclusively bound to plasma", "exclusively bound to plasma proteins", "to plasma proteins >98%", ">98% lennernas 2003", "lennernas 2003 and", "and is subject to", "is subject to pre\u2011systemic clearance", "subject to pre\u2011systemic clearance at", "to pre\u2011systemic clearance at the", "pre\u2011systemic clearance at the gastrointestinal", "clearance at the gastrointestinal tract", "at the gastrointestinal tract and", "the gastrointestinal tract and to", "gastrointestinal tract and to first\u2011pass", "tract and to first\u2011pass hepatic", "and to first\u2011pass hepatic clearance", "first\u2011pass hepatic clearance which", "hepatic clearance which explains", "clearance which explains its", "which explains its low systemic", "explains its low systemic bioavailability", "low systemic bioavailability ~12%", "~12% garcia et", "garcia et al. 2003 .", "et al. 2003 . organic", "al. 2003 . organic anion", "2003 . organic anion transporters", ". organic anion transporters oatp1b1", "anion transporters oatp1b1 oatp1b3", "transporters oatp1b1 oatp1b3 and", "oatp1b1 oatp1b3 and oatp2b1", "oatp1b3 and oatp2b1 encoded", "and oatp2b1 encoded by", "oatp2b1 encoded by slco1b1", "encoded by slco1b1 slco1b3", "slco1b1 slco1b3 and", "slco2b1 respectively are", "respectively are expressed on", "are expressed on the sinusoidal", "expressed on the sinusoidal membrane", "on the sinusoidal membrane of", "the sinusoidal membrane of hepatocytes", "sinusoidal membrane of hepatocytes and", "membrane of hepatocytes and can", "of hepatocytes and can facilitate", "hepatocytes and can facilitate the", "and can facilitate the liver", "can facilitate the liver uptake", "facilitate the liver uptake of", "the liver uptake of drugs", "liver uptake of drugs such", "uptake of drugs such as", "of drugs such as atv", "such as atv kalliokoski", "as atv kalliokoski &", "atv kalliokoski & niemi", "kalliokoski & niemi 2009 .

              in", "& niemi 2009 .

              in hepatocytes", "2009 .

              in hepatocytes and", ".

              in hepatocytes and to", "hepatocytes and to a", "and to a lesser extent", "a lesser extent the", "lesser extent the gi", "extent the gi tract", "gi tract atv", "tract atv can", "atv can be hydroxylated by", "can be hydroxylated by cytochrome", "be hydroxylated by cytochrome p450", "hydroxylated by cytochrome p450 3a4", "cytochrome p450 3a4 cyp3a4", "3a4 cyp3a4 to", "cyp3a4 to hydroxy metabolites", "to hydroxy metabolites or", "hydroxy metabolites or undergo", "metabolites or undergo lactonization", "or undergo lactonization via an", "undergo lactonization via an unstable", "lactonization via an unstable acyl", "via an unstable acyl glucuronide", "an unstable acyl glucuronide intermediate", "unstable acyl glucuronide intermediate to", "acyl glucuronide intermediate to atv", "glucuronide intermediate to atv lactone", "to atv lactone atvl", "lactone atvl mediated", "atvl mediated by ugt1a3", "mediated by ugt1a3 and 1a1.", "by ugt1a3 and 1a1. atvl", "ugt1a3 and 1a1. atvl may", "and 1a1. atvl may also", "1a1. atvl may also be", "atvl may also be hydroxylated", "may also be hydroxylated by", "also be hydroxylated by cyp3a4", "be hydroxylated by cyp3a4 to", "hydroxylated by cyp3a4 to hydroxylactone", "by cyp3a4 to hydroxylactone metabolites.", "cyp3a4 to hydroxylactone metabolites. the", "to hydroxylactone metabolites. the lactone", "hydroxylactone metabolites. the lactone metabolites", "metabolites. the lactone metabolites are", "the lactone metabolites are inactive", "lactone metabolites are inactive against", "metabolites are inactive against hmgcr", "inactive against hmgcr but", "against hmgcr but can", "hmgcr but can be", "but can be hydrolyzed via", "can be hydrolyzed via paraoxonases", "hydrolyzed via paraoxonases pons", "paraoxonases pons to", "pons to their corresponding", "to their corresponding hydroxy acids", "corresponding hydroxy acids which", "hydroxy acids which are", "acids which are active", "which are active against hmgcr.", "are active against hmgcr. elimination", "active against hmgcr. elimination of", "against hmgcr. elimination of atv", "hmgcr. elimination of atv and", "elimination of atv and its", "of atv and its metabolites", "atv and its metabolites is", "and its metabolites is principally", "its metabolites is principally biliary", "metabolites is principally biliary with", "is principally biliary with apparently", "principally biliary with apparently no", "biliary with apparently no significant", "with apparently no significant enterohepatic", "apparently no significant enterohepatic recirculation.", "no significant enterohepatic recirculation. half", "significant enterohepatic recirculation. half life", "recirculation. half life t1/2", "life t1/2 is", "t1/2 is approximately 14", "is approximately 14 h for", "approximately 14 h for atorvastatin", "14 h for atorvastatin and", "h for atorvastatin and 20\u201330", "for atorvastatin and 20\u201330 h", "atorvastatin and 20\u201330 h for", "and 20\u201330 h for its", "20\u201330 h for its metabolites", "for its metabolites schachter", "its metabolites schachter 2005", "metabolites schachter 2005 ." ] }, { "record_id": "GLY_000594_1_1954", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9705677", "r hsa", "hsa 9705677", "r hsa 9705677" ] }, { "record_id": "GLY_000594_1_1954", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 2", "2 targets", "targets pdz", "pdz proteins", "proteins in", "in cell", "cell cell", "cell junction", "sars cov 2", "cov 2 targets", "2 targets pdz", "targets pdz proteins", "pdz proteins in", "proteins in cell", "in cell cell", "cell cell junction", "sars cov 2 targets", "cov 2 targets pdz", "2 targets pdz proteins", "targets pdz proteins in", "pdz proteins in cell", "proteins in cell cell", "in cell cell junction", "sars cov 2 targets pdz", "cov 2 targets pdz proteins", "2 targets pdz proteins in", "targets pdz 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proteins", "encode pbm containing proteins that", "pbm containing proteins that bind", "containing proteins that bind to", "proteins that bind to cellular", "that bind to cellular pdz", "bind to cellular pdz proteins.", "to cellular pdz proteins. viral", "cellular pdz proteins. viral pbms", "pdz proteins. viral pbms target", "proteins. viral pbms target cellular", "viral pbms target cellular pdz", "pbms target cellular pdz containing", "target cellular pdz containing proteins", "cellular pdz containing proteins involved", "pdz containing proteins involved in", "containing proteins involved in tight", "proteins involved in tight junction", "involved in tight junction formation", "tight junction formation cell", "junction formation cell polarity", "formation cell polarity establishment", "cell polarity establishment and", "polarity establishment and apoptosis", "and apoptosis javier rt", "apoptosis javier rt &", "javier rt & rice ap", "rt & rice ap 2011", "& rice ap 2011 ." ] }, { "record_id": "GLY_000594_1_1955", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9754119", "r hsa", "hsa 9754119", "r hsa 9754119" ] }, { "record_id": "GLY_000594_1_1955", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "drug mediated", "mediated inhibition", "inhibition of", "of cdk4/cdk6", "cdk4/cdk6 activity", "drug mediated inhibition", "mediated inhibition of", "inhibition of cdk4/cdk6", "of cdk4/cdk6 activity", "drug mediated inhibition of", "mediated inhibition of cdk4/cdk6", "inhibition of cdk4/cdk6 activity", "drug mediated inhibition of cdk4/cdk6", "mediated inhibition of cdk4/cdk6 activity", "cyclin dependent", "dependent kinases", "kinases cdk4", "cdk4 and", "and cdk6", "cdk6 regulate", "regulate crucial", "crucial steps", "steps in", "in the", "the g1", "g1 phase", "phase of", "of the", "the cell", "cell cycle", "cycle that", "that commit", "commit cells", "cells to", "to 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donnelly", "2006 donnelly et", "donnelly et al. 2013", "al. 2013 pakos", "2013 pakos zebrucka", "pakos zebrucka et al.", "zebrucka et al. 2016", "al. 2016 wek", "2016 wek 2018", "eif2ak4 gcn2 senses", "gcn2 senses amino acid", "senses amino acid deficiency by", "amino acid deficiency by binding", "acid deficiency by binding uncharged", "deficiency by binding uncharged trnas", "by binding uncharged trnas near", "binding uncharged trnas near the", "uncharged trnas near the ribosome", "trnas near the ribosome and", "near the ribosome and responds", "the ribosome and responds by", "ribosome and responds by phosphorylating", "and responds by phosphorylating eif2s1", "by phosphorylating eif2s1 the", "phosphorylating eif2s1 the alpha", "eif2s1 the alpha subunit", "the alpha subunit of the", "alpha subunit of the translation", "subunit of the translation initiation", "of the translation initiation factor", "the translation initiation factor eif2", "initiation factor eif2 inferred", "factor 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misanova", "misanova et", "al. 2006", "hirai et", "al. 2007", "igarashi et", "al. 2008", "2008 .", ". dissociation", "dissociation of", "heme from", "the ki", "ki domain", "domain activates", "activates the", "which autophosphorylates", "in bauer", "bauer et", "al. 2001", "al. 2003", "al. 2011", "and then", "then phosphorylates", "phosphorylates eif2s1", "bhavnani et", "al. 2018", "rabbit homologs", "homologs in", "mouse homologs", "in lu", "lu et", "2011 .
              phosphorylated", ".
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              phosphorylation", ".
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              eif2ak1", ".
              eif2ak1 is", "is also", "also activated", "activated by", "by heat", "heat shock", "oxidative stress", "and osmotic", "osmotic stress", ". the", "the mechanisms", "mechanisms by", "by which", "which these", "these stresses", "stresses act", "act on", "on eif2ak1", "eif2ak1 are", "are independent", "independent of", "heme but", "but are", "are not", "not yet", "yet fully", "fully elucidated.", "elucidated. furthermore", "eif2ak1 is", "is involved", "involved in", "the production", "production of", "of human", "human fetal", "fetal hemoglobin", "eif2ak1 mediated", "mediated stress", "response has", "has emerged", "emerged as", "a potential", "potential therapeutic", "therapeutic target", "target for", "for hemoglobinopathies", "chen and", "zhang 2019", "2019 .
              in", ".
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              phosphorylated", "2011 .
              phosphorylated eifs1", ".
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              phosphorylation", "2019 .
              phosphorylation of", ".
              phosphorylation of eifs1", "of eifs1 activates", "eifs1 activates translation", "activates translation of", "translation of certain", "of certain mrnas", "certain mrnas such", "mrnas such as", "such as atf4", "atf4 atf5", "atf5 and", "ddit3 chop", "chop that", "that have upstream", "have upstream orfs", "orfs inferred", "homologs in harding", "in harding et", "harding et al.", "al. 2000 .", "2000 . atf4", ". atf4 in", "atf4 in turn", "in turn activates", "turn activates programs", "activates programs of", "programs of gene", "of gene expression", "gene expression that", "expression that ameliorate", "that ameliorate effects", "ameliorate effects of", "effects of the", "of the stress", "the stress to", "stress to maintain", "to maintain mitochondrial", "maintain mitochondrial function", "function redox", "homeostasis and", "and erythroid differentiation", "differentiation inferred", "2019 . unresolved", ". unresolved stress", "stress however", "however can", "can eventually lead", "eventually lead to", "lead to apoptosis", "to apoptosis regulated", "apoptosis regulated by", "regulated by ddit3.", "by ddit3. eif2ak1", "ddit3. eif2ak1 also", "eif2ak1 also represses", "also represses mtorc1", "mtorc1 mechanistic", "mechanistic target of", "target of mechanistic", "of mechanistic target", "target of rapamycin", "of rapamycin complex", "rapamycin complex 1", "1 signaling", "signaling via atf4", "via atf4 mediated", "atf4 mediated induction", "mediated induction of", "induction of grb10", "of grb10 as", "grb10 as a", "as a feedback", "a feedback mechanism", "feedback mechanism to", "mechanism to attenuate", "to attenuate erythropoietin", "attenuate erythropoietin mtorc1", "erythropoietin mtorc1 stimulated", "mtorc1 stimulated ineffective", "stimulated ineffective erythropoiesis", "ineffective erythropoiesis in", "erythropoiesis in iron", "in iron deficiency", "iron deficiency anemia", "anemia inferred", "al. 2018 and", "2018 and zhang", "and zhang et.", "zhang et. al.", "et. al. 2019", "al. 2019 .
              eif2ak1", "2019 .
              eif2ak1 is", ".
              eif2ak1 is also", "is also activated", "also activated by", "activated by heat", "by heat shock", "shock arsenite", "arsenite oxidative", "and osmotic stress", "stress inferred", "2001 . the", ". the mechanisms", "the mechanisms by", "mechanisms by which", "by which these", "which these stresses", "these stresses act", "stresses act on", "act on eif2ak1", "on eif2ak1 are", "eif2ak1 are independent", "are independent of", "independent of heme", "of heme but", "heme but are", "but are not", "are not yet", "not yet fully", "yet fully elucidated.", "fully elucidated. furthermore", "furthermore eif2ak1", "eif2ak1 is involved", "is involved in", "involved in the", "in the production", "the production of", "production of human", "of human fetal", "human fetal hemoglobin", "hemoglobin and", "and eif2ak1 mediated", "eif2ak1 mediated stress", "mediated stress response", "stress response has", "response has emerged", "has emerged as", "emerged as a", "as a potential", "a potential therapeutic", "potential therapeutic target", "therapeutic target for", "target for hemoglobinopathies", "hemoglobinopathies reviewed", "in chen and", "chen and zhang", "and zhang 2019", "zhang 2019 .
              in", "2019 .
              in addition", ".
              in addition to", "addition to regulation", "to regulation of", "regulation of erythropoiesis", "erythropoiesis eif2ak1", "eif2ak1 shows effects", "shows effects outside", "effects outside of", "outside of the", "of the erythroid", "the erythroid lineage", "lineage including", "including requirement for", "requirement for the", "for the maturation", "the maturation and", "maturation and functions", "and functions of", "functions of macrophages", "macrophages inferred", "homologs in liu", "in liu et", "liu et al.", "reduction in endoplasmic", "in endoplasmic reticulum", "endoplasmic reticulum stress", "reticulum stress in", "stress in hepatocytes", "hepatocytes activation", "activation of hepatic", "of hepatic expression", "hepatic expression of", "expression of fibroblast", "of fibroblast growth", "fibroblast growth factor", "factor and", "and mediation of", "mediation of translation", "of translation of", "translation of grin2b", "grin2b glun2b.", "glun2b. a subunit", "a subunit of", "subunit of the", "of the nmda", "the nmda receptor", "receptor and", "and bace1 in", "bace1 in the", "in the nervous", "the nervous system", "system reviewed", "reviewed in burwick", "in burwick and", "burwick and aktas", "and aktas 2017", "aktas 2017 .", "2017 . hri", ". hri integrated", "hri integrated stress", "stress response is", "response is activated", "is activated in", "activated in human", "in human cancer", "human cancer cell", "cancer cell lines", "cell lines and", "lines and primary", "and primary multiple", "primary multiple myeloma", "multiple myeloma cells", "cells and", "and has emerged", "as a molecular", "a molecular target", "molecular target of", "target of anticancer", "of anticancer agents", "2017 reviewed", "zhang 2019 .", "the kinases of the", "kinases of the integrated", "of the integrated stress", "the integrated stress response", "integrated stress response phosphorylate", "stress response phosphorylate eif2s1", "phosphorylate eif2s1 eif2", 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autophosphorylates inferred", "autophosphorylates inferred from", "mouse homolog in bauer", "homolog in bauer et", "in bauer et al.", "bauer et al. 2001", "al. 2001 rafie", "2001 rafie kolpin", "kolpin et al. 2003", "al. 2003 igarashi", "2003 igarashi et", "igarashi et al. 2011", "al. 2011 and", "2011 and then", "and then phosphorylates eif2s1", "phosphorylates eif2s1 bhavnani", "eif2s1 bhavnani et", "bhavnani et al. 2018", "al. 2018 inferred", "2018 inferred from", "from the rabbit homologs", "the rabbit homologs in", "rabbit homologs in chefalo", "homologs in chefalo et", "from the mouse homologs", "the mouse homologs in", "mouse homologs in lu", "homologs in lu et", "in lu et al.", "lu et al. 2001", "et al. 2011 .
              phosphorylated", "al. 2011 .
              phosphorylated eifs1", "2011 .
              phosphorylated eifs1 causes", ".
              phosphorylated eifs1 causes a", "eifs1 causes a reduction", "causes a reduction in", "a reduction in general", "reduction in general cellular", "in general cellular translation", "general cellular translation and", "cellular translation and thereby", "translation and thereby coordinates", "and thereby coordinates globin", "thereby coordinates globin synthesis", "coordinates globin synthesis with", "globin synthesis with heme", "synthesis with heme availability", "with heme availability during", "heme availability during erythropoiesis", "during erythropoiesis inferred", "erythropoiesis inferred from", "inferred from mouse knockout", "from mouse knockout in", "mouse knockout in han", "knockout in han et", "in han et al.", "han et al. 2001", "al. 2001 reviewed", "2001 reviewed in", "reviewed in chen et", "in chen et al.", "chen et al. 2014", "et al. 2014 .", "al. 2014 . translation", "2014 . translation of", ". translation of mitochondrial", "translation of mitochondrial and", "of mitochondrial and cytosolic", "mitochondrial and cytosolic ribosomal", "and cytosolic ribosomal proteins", "cytosolic ribosomal proteins is", "ribosomal proteins is most", "proteins is most severely", "is most severely reduced", "severely reduced causing", "reduced causing a", "causing a decrease in", "a decrease in cellular", "decrease in cellular protein", "in cellular protein synthesis", "protein synthesis inferred", "synthesis inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in zhang", "homologs in zhang et", "in zhang et al.", "zhang et al. 2019", "et al. 2019 .", "al. 2019 . lack", "2019 . lack of", ". lack of eif2ak1", "lack of eif2ak1 causes", "of eif2ak1 causes accumulation", "eif2ak1 causes accumulation of", "causes accumulation of unfolded", "accumulation of unfolded globins", "of unfolded globins devoid", "unfolded globins devoid of", "globins devoid of heme", "devoid of heme and", "of heme and consequent", "heme and consequent anemia", "and consequent anemia in", "consequent anemia in iron", "anemia in iron deficient", "in iron deficient mice", "deficient mice inferred", "mice inferred from", "et al. 2001 .", "al. 2001 . activation", "2001 . activation of", ". activation of the", "activation of the cytoplasmic", "of the cytoplasmic unfolded", "the cytoplasmic unfolded protein", "cytoplasmic unfolded protein response", "unfolded protein response and", "protein response and impaired", "response and impaired mitochondrial", "and impaired mitochondrial respiration", "impaired mitochondrial respiration are", "mitochondrial respiration are also", "respiration are also observed", "are also observed in", "also observed in hri", "observed in hri deficiency", "hri deficiency inferred", "deficiency inferred from", "et al. 2019 .
              phosphorylation", "al. 2019 .
              phosphorylation of", "2019 .
              phosphorylation of eifs1", ".
              phosphorylation of eifs1 activates", "of eifs1 activates translation", "eifs1 activates translation of", "activates translation of certain", "translation of certain mrnas", "of certain mrnas such", "certain mrnas such as", "mrnas such as atf4", "as atf4 atf5", "atf5 and ddit3", "and ddit3 chop", "chop that have", "that have upstream orfs", "upstream orfs inferred", "orfs inferred from", "mouse homologs in harding", "homologs in harding et", "in harding et al.", "harding et al. 2000", "et al. 2000 .", "al. 2000 . atf4", "2000 . atf4 in", ". atf4 in turn", "atf4 in turn activates", "in turn activates programs", "turn activates programs of", "activates programs of gene", "programs of gene expression", "of gene expression that", "gene expression that ameliorate", "expression that ameliorate effects", "that ameliorate effects of", "ameliorate effects of the", "effects of the stress", "of the stress to", "the stress to maintain", "stress to maintain mitochondrial", "to maintain mitochondrial function", "mitochondrial function redox", "function redox homeostasis", "redox homeostasis and", "homeostasis and erythroid", "erythroid differentiation inferred", "differentiation inferred from", "al. 2019 . unresolved", "2019 . unresolved stress", "unresolved stress however", "however can eventually", "can eventually lead to", "eventually lead to apoptosis", "lead to apoptosis regulated", "to apoptosis regulated by", "apoptosis regulated by ddit3.", "regulated by ddit3. eif2ak1", "by ddit3. eif2ak1 also", "ddit3. eif2ak1 also represses", "eif2ak1 also represses mtorc1", "represses mtorc1 mechanistic", "mtorc1 mechanistic target", "mechanistic target of mechanistic", "target of mechanistic target", "of mechanistic target of", "mechanistic target of rapamycin", "target of rapamycin complex", "of rapamycin complex 1", "complex 1 signaling", "1 signaling via", "signaling via atf4 mediated", "via atf4 mediated induction", "atf4 mediated induction of", "mediated induction of grb10", "induction of grb10 as", "of grb10 as a", "grb10 as a feedback", "as a feedback mechanism", "a feedback mechanism to", "feedback mechanism to attenuate", "mechanism to attenuate erythropoietin", "to attenuate erythropoietin mtorc1", "attenuate erythropoietin mtorc1 stimulated", "erythropoietin mtorc1 stimulated ineffective", "mtorc1 stimulated ineffective erythropoiesis", "stimulated ineffective erythropoiesis in", "ineffective erythropoiesis in iron", "erythropoiesis in iron deficiency", "in iron deficiency anemia", "deficiency anemia inferred", "anemia inferred from", "zhang et al. 2018", "et al. 2018 and", "al. 2018 and zhang", "2018 and zhang et.", "and zhang et. al.", "zhang et. al. 2019", "et. al. 2019 .
              eif2ak1", "al. 2019 .
              eif2ak1 is", "2019 .
              eif2ak1 is also", ".
              eif2ak1 is also activated", "is also activated by", "also activated by heat", "activated by heat shock", "heat shock arsenite", "arsenite oxidative stress", "stress and", "osmotic stress inferred", "stress inferred from", "al. 2001 . the", "2001 . the mechanisms", ". the mechanisms by", "the mechanisms by which", "mechanisms by which these", "by which these stresses", "which these stresses act", "these stresses act on", "stresses act on eif2ak1", "act on eif2ak1 are", "on eif2ak1 are independent", "eif2ak1 are independent of", "are independent of heme", "independent of heme but", "of heme but are", "heme but are not", "but are not yet", "are not yet fully", "not yet fully elucidated.", "yet fully elucidated. furthermore", "elucidated. furthermore eif2ak1", "furthermore eif2ak1 is", "eif2ak1 is involved in", "is involved in the", "involved in the production", "in the production of", "the production of human", "production of human fetal", "of human fetal hemoglobin", "fetal hemoglobin and", "hemoglobin and eif2ak1", "and eif2ak1 mediated stress", "eif2ak1 mediated stress response", "mediated stress response has", "stress response has emerged", "response has emerged as", "has emerged as a", "emerged as a potential", "as a potential therapeutic", "a potential therapeutic target", "potential therapeutic target for", "therapeutic target for hemoglobinopathies", "for hemoglobinopathies reviewed", "hemoglobinopathies reviewed in", "reviewed in chen and", "in chen and zhang", "chen and zhang 2019", "and zhang 2019 .
              in", "zhang 2019 .
              in addition", "2019 .
              in addition to", ".
              in addition to regulation", "addition to regulation of", "to regulation of erythropoiesis", "of erythropoiesis eif2ak1", "erythropoiesis eif2ak1 shows", "eif2ak1 shows effects outside", "shows effects outside of", "effects outside of the", "outside of the erythroid", "of the erythroid lineage", "erythroid lineage including", "lineage including requirement", "including requirement for the", "requirement for the maturation", "for the maturation and", "the maturation and functions", "maturation and functions of", "and functions of macrophages", "of macrophages inferred", "macrophages inferred from", "mouse homologs in liu", "homologs in liu et", "in liu et al.", "liu et al. 2007", "reduction in endoplasmic reticulum", "in endoplasmic reticulum stress", "endoplasmic reticulum stress in", "reticulum stress in hepatocytes", "in hepatocytes activation", "hepatocytes activation of", "activation of hepatic expression", "of hepatic expression of", "hepatic expression of fibroblast", "expression of fibroblast growth", "of fibroblast growth factor", "growth factor and", "factor and mediation", "and mediation of translation", "mediation of translation of", "of translation of grin2b", "of grin2b glun2b.", "grin2b glun2b. a", "glun2b. a subunit of", "a subunit of the", "subunit of the nmda", "of the nmda receptor", "nmda receptor and", "receptor and bace1", "and bace1 in the", "bace1 in the nervous", "in the nervous system", "nervous system reviewed", "system reviewed in", "reviewed in burwick and", "in burwick and aktas", "burwick and aktas 2017", "and aktas 2017 .", "aktas 2017 . hri", "2017 . hri integrated", ". hri integrated stress", "hri integrated stress response", "integrated stress response is", "stress response is activated", "response is activated in", "is activated in human", "activated in human cancer", "in human cancer cell", "human cancer cell lines", "cancer cell lines and", "cell lines and primary", "lines and primary multiple", "and primary multiple myeloma", "primary multiple myeloma cells", "myeloma cells and", "cells and has", "and has emerged as", "emerged as a molecular", "as a molecular target", "a molecular target of", "molecular target of anticancer", "target of anticancer agents", "agents reviewed", "aktas 2017 reviewed", "2017 reviewed in", "and zhang 2019 .", "the kinases of the integrated", "kinases of the integrated stress", "of the integrated stress response", "the integrated stress response phosphorylate", "integrated stress response phosphorylate eif2s1", "response phosphorylate eif2s1 eif2", "phosphorylate eif2s1 eif2 alpha", "eif2 alpha to regulate", "alpha to regulate cellular", "to regulate cellular translation. the", "regulate cellular translation. the kinases", "cellular translation. the kinases comprise", "translation. the kinases comprise perk", "kinases comprise perk also", "comprise perk also called", "perk also called eif2ak3", "called eif2ak3 which", "eif2ak3 which responds", "which responds to unfolded protein", "responds to unfolded protein in", "to unfolded protein in the", "unfolded protein in the endoplasmic", "protein in the endoplasmic reticulum", "the endoplasmic reticulum eif2ak2", "reticulum eif2ak2 also", "eif2ak2 also called pkr", "called pkr which", "pkr which responds", "which responds to cytosolic double", "responds to cytosolic double stranded", "to cytosolic double stranded rna", "double stranded rna eif2ak4", "rna eif2ak4 also", "eif2ak4 also called gcn2", "called gcn2 which", "gcn2 which responds", "which responds to amino acid", "responds to amino acid deficiency", "amino acid deficiency and", "acid deficiency and eif2ak1", "and eif2ak1 also called", "eif2ak1 also called heme", "also called heme regulated inhibitor", "heme regulated inhibitor hri", "inhibitor hri and", "hri and heme controlled", "heme controlled repressor hcr", "hcr which responds", "which responds to heme deficiency", "responds to heme deficiency and", "to heme deficiency and cytosolic", "heme deficiency and cytosolic unfolded", "deficiency and cytosolic unfolded protein.", "and cytosolic unfolded protein. each", "cytosolic unfolded protein. each molecule", "unfolded protein. each molecule of", "protein. each molecule of eif2ak1", "each molecule of eif2ak1 binds", "molecule of eif2ak1 binds two", "of eif2ak1 binds two molecules", "eif2ak1 binds two molecules of", "binds two molecules of heme", "molecules of heme one", "of heme one bound", "heme one bound near", "one bound near the n", "bound near the n terminus", "near the n terminus and", "the n terminus and one", "n terminus and one bound", "terminus and one bound at", "and one bound at the", "one bound at the kinase", "bound at the kinase insert", "the kinase insert ki", "insert ki domain", "ki domain that inhibits", "domain that inhibits the kinase", "that inhibits the kinase activity", "inhibits the kinase activity of", "the kinase activity of eif2ak1", "activity of eif2ak1 inferred", "of eif2ak1 inferred from", "eif2ak1 inferred from the", "inferred from the rabbit homolog", "from the rabbit homolog in", "the rabbit homolog in chefalo", "rabbit homolog in chefalo et", "homolog in chefalo et al.", "in chefalo et al. 1998", "et al. 1998 rafie", "al. 1998 rafie kolpin", "1998 rafie kolpin et", "rafie kolpin et al. 2000", "et al. 2000 inferred", "al. 2000 inferred from", "2000 inferred from the", "inferred from the mouse homolog", "from the mouse homolog in", "the mouse homolog in misanova", "mouse homolog in misanova et", "homolog in misanova et al.", "in misanova et al. 2006", "et al. 2006 hirai", "al. 2006 hirai et", "2006 hirai et al.", "et al. 2007 igarashi", "al. 2007 igarashi et", "2007 igarashi et al.", "igarashi et al. 2008 .", "et al. 2008 . dissociation", "al. 2008 . dissociation of", "2008 . dissociation of heme", ". dissociation of heme from", "dissociation of heme from the", "of heme from the ki", "heme from the ki domain", "from the ki domain activates", "the ki domain activates the", "ki domain activates the kinase", "domain activates the kinase activity", "activates the kinase activity of", "activity of eif2ak1 which", "of eif2ak1 which autophosphorylates", "which autophosphorylates inferred from", "autophosphorylates inferred from the", "the mouse homolog in bauer", "mouse homolog in bauer et", "homolog in bauer et al.", "in bauer et al. 2001", "et al. 2001 rafie", "al. 2001 rafie kolpin", "2001 rafie kolpin et", "rafie kolpin et al. 2003", "et al. 2003 igarashi", "al. 2003 igarashi et", "2003 igarashi et al.", "et al. 2011 and", "al. 2011 and then", "2011 and then phosphorylates", "then phosphorylates eif2s1 bhavnani", "phosphorylates eif2s1 bhavnani et", "eif2s1 bhavnani et al.", "et al. 2018 inferred", "al. 2018 inferred from", "2018 inferred from the", "inferred from the rabbit homologs", "from the rabbit homologs in", "the rabbit homologs in chefalo", "rabbit homologs in chefalo et", "homologs in chefalo et al.", "inferred from the mouse homologs", "from the mouse homologs in", "the mouse homologs in lu", "mouse homologs in lu et", "homologs in lu et al.", "in lu et al. 2001", "igarashi et al. 2011 .
              phosphorylated", "et al. 2011 .
              phosphorylated eifs1", "al. 2011 .
              phosphorylated eifs1 causes", "2011 .
              phosphorylated eifs1 causes a", ".
              phosphorylated eifs1 causes a reduction", "eifs1 causes a reduction in", "causes a reduction in general", "a reduction in general cellular", "reduction in general cellular translation", "in general cellular translation and", "general cellular translation and thereby", "cellular translation and thereby coordinates", "translation and thereby coordinates globin", "and thereby coordinates globin synthesis", "thereby coordinates globin synthesis with", "coordinates globin synthesis with heme", "globin synthesis with heme availability", "synthesis with heme availability during", "with heme availability during erythropoiesis", "availability during erythropoiesis inferred", "during erythropoiesis inferred from", "erythropoiesis inferred from mouse", "inferred from mouse knockout in", "from mouse knockout in han", "mouse knockout in han et", "knockout in han et al.", "in han et al. 2001", "et al. 2001 reviewed", "al. 2001 reviewed in", "2001 reviewed in chen", "reviewed in chen et al.", "in chen et al. 2014", "chen et al. 2014 .", "et al. 2014 . translation", "al. 2014 . translation of", "2014 . translation of mitochondrial", ". translation of mitochondrial and", "translation of mitochondrial and cytosolic", "of mitochondrial and cytosolic ribosomal", "mitochondrial and cytosolic ribosomal proteins", "and cytosolic ribosomal proteins is", "cytosolic ribosomal proteins is most", "ribosomal proteins is most severely", "proteins is most severely reduced", "most severely reduced causing", "severely reduced causing a", "reduced causing a decrease", "causing a decrease in cellular", "a decrease in cellular protein", "decrease in cellular protein synthesis", "cellular protein synthesis inferred", "protein synthesis inferred from", "synthesis inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in zhang", "mouse homologs in zhang et", "homologs in zhang et al.", "in zhang et al. 2019", "zhang et al. 2019 .", "et al. 2019 . lack", "al. 2019 . lack of", "2019 . lack of eif2ak1", ". lack of eif2ak1 causes", "lack of eif2ak1 causes accumulation", "of eif2ak1 causes accumulation of", "eif2ak1 causes accumulation of unfolded", "causes accumulation of unfolded globins", "accumulation of unfolded globins devoid", "of unfolded globins devoid of", "unfolded globins devoid of heme", "globins devoid of heme and", "devoid of heme and consequent", "of heme and consequent anemia", "heme and consequent anemia in", "and consequent anemia in iron", "consequent anemia in iron deficient", "anemia in iron deficient mice", "iron deficient mice inferred", "deficient mice inferred from", "mice inferred from mouse", "han et al. 2001 .", "et al. 2001 . activation", "al. 2001 . activation of", "2001 . activation of the", ". activation of the cytoplasmic", "activation of the cytoplasmic unfolded", "of the cytoplasmic unfolded protein", "the cytoplasmic unfolded protein response", "cytoplasmic unfolded protein response and", "unfolded protein response and impaired", "protein response and impaired mitochondrial", "response and impaired mitochondrial respiration", "and impaired mitochondrial respiration are", "impaired mitochondrial respiration are also", "mitochondrial respiration are also observed", "respiration are also observed in", "are also observed in hri", "also observed in hri deficiency", "in hri deficiency inferred", "hri deficiency inferred from", "deficiency inferred from mouse", "zhang et al. 2019 .
              phosphorylation", "et al. 2019 .
              phosphorylation of", "al. 2019 .
              phosphorylation of eifs1", "2019 .
              phosphorylation of eifs1 activates", ".
              phosphorylation of eifs1 activates translation", "of eifs1 activates translation of", "eifs1 activates translation of certain", "activates translation of certain mrnas", "translation of certain mrnas such", "of certain mrnas such as", "certain mrnas such as atf4", "such as atf4 atf5", "atf4 atf5 and", "ddit3 chop that", "chop that have upstream", "have upstream orfs inferred", "upstream orfs inferred from", "orfs inferred from mouse", "from mouse homologs in harding", "mouse homologs in harding et", "homologs in harding et al.", "in harding et al. 2000", "harding et al. 2000 .", "et al. 2000 . atf4", "al. 2000 . atf4 in", "2000 . atf4 in turn", ". atf4 in turn activates", "atf4 in turn activates programs", "in turn activates programs of", "turn activates programs of gene", "activates programs of gene expression", "programs of gene expression that", "of gene expression that ameliorate", "gene expression that ameliorate effects", "expression that ameliorate effects of", "that ameliorate effects of the", "ameliorate effects of the stress", "effects of the stress to", "of the stress to maintain", "the stress to maintain mitochondrial", "stress to maintain mitochondrial function", "maintain mitochondrial function redox", "mitochondrial function redox homeostasis", "redox homeostasis and erythroid", "homeostasis and erythroid differentiation", "and erythroid differentiation inferred", "erythroid differentiation inferred from", "differentiation inferred from mouse", "et al. 2019 . unresolved", "al. 2019 . unresolved stress", ". unresolved stress however", "stress however can", "however can eventually lead", "can eventually lead to apoptosis", "eventually lead to apoptosis regulated", "lead to apoptosis regulated by", "to apoptosis regulated by ddit3.", "apoptosis regulated by ddit3. eif2ak1", "regulated by ddit3. eif2ak1 also", "by ddit3. eif2ak1 also represses", "ddit3. eif2ak1 also represses mtorc1", "also represses mtorc1 mechanistic", "represses mtorc1 mechanistic target", "mtorc1 mechanistic target of", "mechanistic target of mechanistic target", "target of mechanistic target of", "of mechanistic target of rapamycin", "mechanistic target of rapamycin complex", "target of rapamycin complex 1", "rapamycin complex 1 signaling", "complex 1 signaling via", "1 signaling via atf4", "signaling via atf4 mediated induction", "via atf4 mediated induction of", "atf4 mediated induction of grb10", "mediated induction of grb10 as", "induction of grb10 as a", "of grb10 as a feedback", "grb10 as a feedback mechanism", "as a feedback mechanism to", "a feedback mechanism to attenuate", "feedback mechanism to attenuate erythropoietin", "mechanism to attenuate erythropoietin mtorc1", "to attenuate erythropoietin mtorc1 stimulated", "attenuate erythropoietin mtorc1 stimulated ineffective", "erythropoietin mtorc1 stimulated ineffective erythropoiesis", "mtorc1 stimulated ineffective erythropoiesis in", "stimulated ineffective erythropoiesis in iron", "ineffective erythropoiesis in iron deficiency", "erythropoiesis in iron deficiency anemia", "iron deficiency anemia inferred", "deficiency anemia inferred from", "anemia inferred from mouse", "in zhang et al. 2018", "zhang et al. 2018 and", "et al. 2018 and zhang", "al. 2018 and zhang et.", "2018 and zhang et. al.", "and zhang et. al. 2019", "zhang et. al. 2019 .
              eif2ak1", "et. al. 2019 .
              eif2ak1 is", "al. 2019 .
              eif2ak1 is also", "2019 .
              eif2ak1 is also activated", ".
              eif2ak1 is also activated by", "is also activated by heat", "also activated by heat shock", "by heat shock arsenite", "shock arsenite oxidative", "oxidative stress and", "stress and osmotic", "and osmotic stress inferred", "osmotic stress inferred from", "stress inferred from mouse", "from mouse homologs in lu", "lu et al. 2001 .", "et al. 2001 . the", "al. 2001 . the mechanisms", "2001 . the mechanisms by", ". the mechanisms by which", "the mechanisms by which these", "mechanisms by which these stresses", "by which these stresses act", "which these stresses act on", "these stresses act on eif2ak1", "stresses act on eif2ak1 are", "act on eif2ak1 are independent", "on eif2ak1 are independent of", "eif2ak1 are independent of heme", "are independent of heme but", "independent of heme but are", "of heme but are not", "heme but are not yet", "but are not yet fully", "are not yet fully elucidated.", "not yet fully elucidated. furthermore", "fully elucidated. furthermore eif2ak1", "elucidated. furthermore eif2ak1 is", "furthermore eif2ak1 is involved", "eif2ak1 is involved in the", "is involved in the production", "involved in the production of", "in the production of human", "the production of human fetal", "production of human fetal hemoglobin", "human fetal hemoglobin and", "fetal hemoglobin and eif2ak1", "hemoglobin and eif2ak1 mediated", "and eif2ak1 mediated stress response", "eif2ak1 mediated stress response has", "mediated stress response has emerged", "stress response has emerged as", "response has emerged as a", "has emerged as a potential", "emerged as a potential therapeutic", "as a potential therapeutic target", "a potential therapeutic target for", "potential therapeutic target for hemoglobinopathies", "target for hemoglobinopathies reviewed", "for hemoglobinopathies reviewed in", "hemoglobinopathies reviewed in chen", "reviewed in chen and zhang", "in chen and zhang 2019", "chen and zhang 2019 .
              in", "and zhang 2019 .
              in addition", "zhang 2019 .
              in addition to", "2019 .
              in addition to regulation", ".
              in addition to regulation of", "addition to regulation of erythropoiesis", "regulation of erythropoiesis eif2ak1", "of erythropoiesis eif2ak1 shows", "erythropoiesis eif2ak1 shows effects", "eif2ak1 shows effects outside of", "shows effects outside of the", "effects outside of the erythroid", "outside of the erythroid lineage", "the erythroid lineage including", "erythroid lineage including requirement", "lineage including requirement for", "including requirement for the maturation", "requirement for the maturation and", "for the maturation and functions", "the maturation and functions of", "maturation and functions of macrophages", "functions of macrophages inferred", "of macrophages inferred from", "macrophages inferred from mouse", "from mouse homologs in liu", "mouse homologs in liu et", "homologs in liu et al.", "in liu et al. 2007", "2007 reduction", "reduction in endoplasmic reticulum stress", "in endoplasmic reticulum stress in", "endoplasmic reticulum stress in hepatocytes", "stress in hepatocytes activation", "in hepatocytes activation of", "hepatocytes activation of hepatic", "activation of hepatic expression of", "of hepatic expression of fibroblast", "hepatic expression of fibroblast growth", "expression of fibroblast growth factor", "fibroblast growth factor and", "growth factor and mediation", "factor and mediation of", "and mediation of translation of", "mediation of translation of grin2b", "translation of grin2b glun2b.", "of grin2b glun2b. a", "grin2b glun2b. a subunit", "glun2b. a subunit of the", "a subunit of the nmda", "subunit of the nmda receptor", "the nmda receptor and", "nmda receptor and bace1", "receptor and bace1 in", "and bace1 in the nervous", "bace1 in the nervous system", "the nervous system reviewed", "nervous system reviewed in", "system reviewed in burwick", "reviewed in burwick and aktas", "in burwick and aktas 2017", "burwick and aktas 2017 .", "and aktas 2017 . hri", "aktas 2017 . hri integrated", "2017 . hri 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              schwann cells", ".
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              schwann", "2015 .
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formation in patients with", "formation in patients with hae", "in patients with hae is", "patients with hae is primarily", "with hae is primarily caused", "hae is primarily caused by", "is primarily caused by a", "primarily caused by a transient", "caused by a transient increased", "by a transient increased bradykinin", "a transient increased bradykinin release", "transient increased bradykinin release from", "increased bradykinin release from high", "bradykinin release from high molecular", "release from high molecular weight", "from high molecular weight kininogen", "molecular weight kininogen hk", "kininogen hk due", "hk due to uncontrolled", "due to uncontrolled activation of", "to uncontrolled activation of the", "uncontrolled activation of the coagulation", "activation of the coagulation factor", "of the coagulation factor xii", "coagulation factor xii fxii", "xii fxii dependent", "fxii dependent kallikrein kinin", "kallikrein kinin system kks", "kks bossi f", "bossi f et al. 2009", "et al. 2009 kaplan", "al. 2009 kaplan ap", "2009 kaplan ap 2010", "kaplan ap 2010 suffritti", "ap 2010 suffritti c", "2010 suffritti c et", "suffritti c et al. 2014:", "c et al. 2014: zuraw", "et al. 2014: zuraw bl", "al. 2014: zuraw bl &", "2014: zuraw bl & christiansen", "zuraw bl & christiansen sc", "bl & christiansen sc 2016", "& christiansen sc 2016 .", "christiansen sc 2016 . angioedema", "sc 2016 . angioedema initiated", "2016 . angioedema initiated by", ". angioedema initiated by bradykinin", "angioedema initiated by bradykinin is", "initiated by bradykinin is usually", "by bradykinin is usually associated", "bradykinin is usually associated with", "is usually associated with serping1", "associated with serping1 c1", "with serping1 c1 inh", "c1 inh deficiency. serping1", "inh deficiency. serping1 is", "deficiency. serping1 is the major", "serping1 is the major regulator", "is the major regulator of", "the major regulator of the", "major regulator of the contact", "regulator of the contact system.", "of the contact system. more", "the contact system. more rarely", "system. more rarely hae", "more rarely hae occurs", "rarely hae occurs in", "hae occurs in individuals with", "occurs in individuals with normal", "in individuals with normal serping1", "individuals with normal serping1 activity", "normal serping1 activity and", "serping1 activity and has", "activity and has been", "and has been linked to", "has been linked to mutations", "been linked to mutations in", "linked to mutations in other", "to mutations in other proteins", "in other proteins including", "other proteins including fxii", "fxii plasminogen and", "and angiopoietin magerl m", "angiopoietin magerl m et", "magerl m et al. 2017", "et al. 2017 zuraw", "al. 2017 zuraw bl", "2017 zuraw bl 2018", "zuraw bl 2018 ivanov", "bl 2018 ivanov i", "2018 ivanov i et", "ivanov i et al. 2019", "i et al. 2019 .", "et al. 2019 . substitution", "al. 2019 . substitution of", "2019 . substitution of threonine", ". substitution of threonine 328", "substitution of threonine 328 by", "of threonine 328 by either", "threonine 328 by either a", "328 by either a lysine", "by either a lysine or", "either a lysine or an", "a lysine or an arginine", "lysine or an arginine residue", "an arginine residue t328k", "arginine residue t328k or", "residue t328k or t328r", "t328k or t328r in", "or t328r in the", "t328r in the fxii", "in the fxii proline rich", "the fxii proline rich region", "fxii proline rich region has", "proline rich region has been", "rich region has been identified", "region has been identified in", "has been identified in several", "been identified in several families", "identified in several families with", "in several families with hae", "several families with hae and", "families with hae and normal", "with hae and normal serping1.", "hae and normal serping1. fxii", "and normal serping1. fxii t328k", "normal serping1. fxii t328k or", "serping1. fxii t328k or t328r", "fxii t328k or t328r variants", "t328k or t328r variants change", "or t328r variants change protein", "t328r variants change protein glycosylation", "variants change protein glycosylation and", "change protein glycosylation and introduce", "protein glycosylation and introduce a", "glycosylation and introduce a new", "and introduce a new site", "introduce a new site that", "a new site that is", "new site that is sensitive", "site that is sensitive to", "that is sensitive to enzymatic", "is sensitive to enzymatic cleavage", "sensitive to enzymatic cleavage by", "to enzymatic cleavage by fibrinolytic", "enzymatic cleavage by fibrinolytic and", "cleavage by fibrinolytic and coagulation", "by fibrinolytic and coagulation proteases", "fibrinolytic and coagulation proteases such", "and coagulation proteases such as", "coagulation proteases such as plasmin", "such as plasmin thrombin", "plasmin thrombin or", "or fxia de maat", "fxia de maat s", "de maat s et al.", "maat s et al. 2016", "et al. 2016 ivanov", "al. 2016 ivanov i", "2016 ivanov i et", "et al. 2019 . the", "al. 2019 . the intrinsic", "2019 . the intrinsic capacity", ". the intrinsic capacity of", "the intrinsic capacity of the", "intrinsic capacity of the truncated", "capacity of the truncated form", "of the truncated form of", "the truncated form of fxii", "form of fxii 329", "of fxii 329 615", "329 615 also", "615 also known", "known as \u03b4fxii to", "as \u03b4fxii to convert", "\u03b4fxii to convert prekallikrein", "to convert prekallikrein to kallikrein", "convert prekallikrein to kallikrein is", "prekallikrein to kallikrein is greater", "to kallikrein is greater than", "kallikrein is greater than that", "is greater than that of", "greater than that of fxii", "than that of fxii leading", "that of fxii leading to", "of fxii leading to more", "fxii leading to more kallikrein", "leading to more kallikrein generated", "to more kallikrein generated early", "more kallikrein generated early during", "kallikrein generated early during reciprocal", "generated early during reciprocal activation", "during reciprocal activation ivanov", "reciprocal activation ivanov i", "activation ivanov i et", "et al. 2019 . second", "2019 . second fxii", "second fxii 329", "329 615 is a", "615 is a better", "is a better kallikrein substrate", "a better kallikrein substrate than", "better kallikrein substrate than is", "kallikrein substrate than is fxii.", "substrate than is fxii. the", "than is fxii. the accelerated", "is fxii. the accelerated kallikrein/fxii", "fxii. the accelerated kallikrein/fxii activation", "the accelerated kallikrein/fxii activation with", "accelerated kallikrein/fxii activation with truncated", "kallikrein/fxii activation with truncated fxii", "with truncated fxii 329", "truncated fxii 329 615", "329 615 appears to", "615 appears to overwhelm", "appears to overwhelm the regulatory", "to overwhelm the regulatory function", "overwhelm the regulatory function of", "the regulatory function of serping1", "regulatory function of serping1 at", "function of serping1 at normal", "of serping1 at normal plasma", "serping1 at normal plasma levels", "at normal plasma levels leading", "normal plasma levels leading to", "plasma levels leading to uncontrolled", "levels leading to uncontrolled bradykinin", "leading to uncontrolled bradykinin formation", "uncontrolled bradykinin formation de", "bradykinin formation de maat", "formation de maat s", "et al. 2019 . binding", "al. 2019 . binding of", "2019 . binding of the", ". binding of the proinflammatory", "binding of the proinflammatory peptide", "of the proinflammatory peptide hormone", "the proinflammatory peptide hormone bradykinin", "proinflammatory peptide hormone bradykinin to", "peptide hormone bradykinin to the", "hormone bradykinin to the bradykinin", "bradykinin to the bradykinin b2", "to the bradykinin b2 receptor", "bradykinin b2 receptor b2r", "receptor b2r activates", "b2r activates various proinflammatory", "activates various proinflammatory signaling pathways", "various proinflammatory signaling pathways that", "proinflammatory signaling pathways that increase", "signaling pathways that increase vascular", "pathways that increase vascular permeability", "that increase vascular permeability and", "increase vascular permeability and fluid", "vascular permeability and fluid efflux.", "permeability and fluid efflux. an", "and fluid efflux. an excessive", "fluid efflux. an excessive formation", "efflux. an excessive formation of", "an excessive formation of bradykinin", "excessive formation of bradykinin due", "formation of bradykinin due to", "of bradykinin due to uncontrolled", "bradykinin due to uncontrolled activation", "to uncontrolled activation of fxii", "uncontrolled activation of fxii dependent", "activation of fxii dependent kks", "of fxii dependent kks causes", "fxii dependent kks causes increased", "dependent kks causes increased vascular", "kks causes increased vascular permeability", "causes increased vascular permeability at", "increased vascular permeability at the", "vascular permeability at the level", "permeability at the level of", "at the level of the", "the level of the postcapillary", "level of the postcapillary venule", "of the postcapillary venule and", "the postcapillary venule and results", "postcapillary venule and results in", "venule and results in hae", "results in hae zuraw", "in hae zuraw bl", "hae zuraw bl &", "christiansen sc 2016 de", "sc 2016 de maat", "2016 de maat s" ] }, { "record_id": "GLY_000594_1_1981", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9657689", "r hsa", "hsa 9657689", "r hsa 9657689" ] }, { "record_id": "GLY_000594_1_1981", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective serping1", "serping1 causes", "causes hereditary", "hereditary angioedema", "defective serping1 causes", "serping1 causes hereditary", "causes hereditary angioedema", "defective serping1 causes hereditary", "serping1 causes hereditary angioedema", "defective serping1 causes hereditary angioedema", "the reciprocal", "reciprocal activation", "activation is", "is initiated", "initiated when", "when zymogen", "zymogen factor", "factor xii", "f12 or", "or fxii", "binds to", "to a", "a negatively", "negatively charged", "charged surface", "which induces", "induces fxii", "fxii autoactivation.", "autoactivation. activated", "activated fxii", "converts prekallikrein", "to kallikrein", "which proteolytically", "proteolytically liberates", "liberates bradykinin", "bradykinin from", "from high", "high molecular", "molecular weight", "weight kininogen", "renne t", "t 2012", "t et", "et al.", "al. 2012", "maas c", "c et", "al. 2011", "2011 .", ". kallikrein", "kallikrein also", "also activates", "activates fxii", "fxii to", "to produce", "produce more", "more fxiia", "initially .", ". fxiia", "fxiia and", "and kallikrein", "kallikrein reciprocally", "reciprocally activate", "activate their", "their zymogens", "zymogens and", "and thus", "thus generate", "generate a", "a positive", "positive feedback", "feedback loop.", "loop. in", "in the", "the presence", "presence of", "of sufficient", "sufficient amounts", "amounts of", "of active", "active enzyme", "fxiia also", "also generates", "generates active", "active factor", "factor xi", "to potentiate", "potentiate the", "the intrinsic", "intrinsic coagulation", "coagulation pathway.", "pathway. all", "all of", "of these", "these enzymatic", "enzymatic steps", "steps are", "are normally", "normally inhibited", "inhibited by", "by c1", "c1 esterase", "esterase inhibitor", "c1 inh", "encoded by", "by the", "the serping1", "serping1 gene", "gene .

              binding", ".

              binding of", "of the", "the proinflammatory", "proinflammatory peptide", "peptide hormone", "hormone bradykinin", "bradykinin to", "to the", "the bradykinin", "bradykinin b2", "b2 receptor", "activates various", "various proinflammatory", "proinflammatory signaling", "signaling pathways", "pathways that", "that increase", "increase vascular", "vascular permeability", "permeability and", "and fluid", "fluid efflux.", "efflux. an", "an excessive", "excessive formation", "formation of", "of bradykinin", "bradykinin due", "due to", "to uncontrolled", "uncontrolled activation", "activation of", "the coagulation", "coagulation factor", "dependent kallikrein", "kallikrein kinin", "kinin system", "system causes", "causes increased", "increased vascular", "permeability at", "at the", "the level", "level of", "the postcapillary", "postcapillary venule", "venule and", "and results", "results in", "in hereditary", "bossi f", "f et", "al. 2009", "kaplan ap", "ap 2010", "suffritti c", "al. 2014:", "2014: zuraw", "zuraw bl", "bl &", "& christiansen", "christiansen sc", "sc 2016", "2016 .", ". hae", "hae is", "is a", "a rare", "rare life", "life threatening", "threatening inherited", "inherited edema", "edema disorder", "disorder that", "that is", "is characterized", "characterized by", "by recurrent", "recurrent episodes", "episodes of", "of localized", "localized edema", "edema of", "the skin", "skin or", "or of", "the mucosa", "mucosa of", "the gastrointestinal", "gastrointestinal tract", "tract or", "or upper", "upper airway.", "airway. angioedema", "angioedema initiated", "initiated by", "by bradykinin", "bradykinin is", "is usually", "usually associated", "associated with", "with serping1", "deficiency. thus", "a major", "major role", "role of", "of serping1", "is to", "to prevent", "prevent the", "the development", "development of", "of excessive", "excessive vascular", "vascular permeability.", "permeability. more", "more rarely", "hae occurs", "occurs in", "in individuals", "individuals with", "with normal", "normal serping1", "serping1 activity", "linked to", "to mutations", "mutations in", "in other", "other proteins", "including fxii", "and angiopoietin", "magerl m", "m et", "al. 2017", "bl 2018", "ivanov i", "i et", "al. 2019", "2019 .", ". patients", "patients with", "with hae", "hae are", "are heterozygous", "heterozygous for", "for deficiency", "deficiency of", "of serping1.the", "serping1.the disease", "has an", "an autosomal", "autosomal dominant", "dominant inheritance", "inheritance and", "and may", "may result", "result from", "from lack", "lack of", "of expression", "expression of", "serping1 from", "from one", "one allele", "type 1", "1 hae", "or from", "from expression", "of a", "a nonfunctional", "nonfunctional serping1", "serping1 protein", "type 2", "2 hae", "hae .", ". this", "this classification", "classification has", "has however", "however been", "been challenged", "challenged by", "by observations", "observations of", "of intermediary", "intermediary hae", "hae types", "that can", "can arise", "when small", "small amounts", "of dysfunctional", "dysfunctional serping1", "serping1 is", "is present", "present in", "the blood", "blood stream", "eldering e", "e et", "al. 1995", "verpy e", "madsen de", "de et", "al. 2014", "2014 .", "the reciprocal activation", "reciprocal activation is", "activation is initiated", "is initiated when", "initiated when zymogen", "when zymogen factor", "zymogen factor xii", "xii f12", "f12 or fxii", "fxii binds", "binds to a", "to a negatively", "a negatively charged", "negatively charged surface", "surface which", "which induces fxii", "induces fxii autoactivation.", "fxii autoactivation. activated", "autoactivation. activated fxii", "fxii fxiia", "fxiia converts", "prekallikrein pk", "pk to", "kallikrein which", "which proteolytically liberates", "proteolytically liberates bradykinin", "liberates bradykinin from", "bradykinin from high", "from high molecular", "high molecular weight", "molecular weight kininogen", "kininogen hk", "renne t 2012", "2012 renne", "renne t et", "t et al.", "et al. 2012", "2012 maas", "maas c et", "c et al.", "et al. 2011", "al. 2011 .", "2011 . kallikrein", ". kallikrein also", "kallikrein also activates", "also activates fxii", "activates fxii to", "fxii to produce", "to produce more", "produce more fxiia", "fxiia initially", "initially . fxiia", ". fxiia and", "fxiia and kallikrein", "and kallikrein reciprocally", "kallikrein reciprocally activate", "reciprocally activate their", "activate their zymogens", "their zymogens and", "zymogens and thus", "and thus generate", "thus generate a", "generate a positive", "a positive feedback", "positive feedback loop.", "feedback loop. in", "loop. in the", "in the presence", "the presence of", "presence of sufficient", "of sufficient amounts", "sufficient amounts of", "amounts of active", "of active enzyme", "enzyme fxiia", "fxiia also generates", "also generates active", "generates active factor", "active factor xi", "xi fxia", "fxia to", "to potentiate the", "potentiate the intrinsic", "the intrinsic coagulation", "intrinsic coagulation pathway.", "coagulation pathway. all", "pathway. all of", "all of these", "of these enzymatic", "these enzymatic steps", "enzymatic steps are", "steps are normally", "are normally inhibited", "normally inhibited by", "inhibited by c1", "by c1 esterase", "c1 esterase inhibitor", "inhibitor c1", "inh encoded", "encoded by the", "by the serping1", "the serping1 gene", "serping1 gene .

              binding", "gene .

              binding of", ".

              binding of the", "of the proinflammatory", "the proinflammatory peptide", "proinflammatory peptide hormone", "peptide hormone bradykinin", "hormone bradykinin to", "bradykinin to the", "to the bradykinin", "the bradykinin b2", "bradykinin b2 receptor", "receptor b2r", "b2r activates", "activates various proinflammatory", "various proinflammatory signaling", "proinflammatory signaling pathways", "signaling pathways that", "pathways that increase", "that increase vascular", "increase vascular permeability", "vascular permeability and", "permeability and fluid", "and fluid efflux.", "fluid efflux. an", "efflux. an excessive", "an excessive formation", "excessive formation of", "formation of bradykinin", "of bradykinin due", "bradykinin due to", "due to uncontrolled", "to uncontrolled activation", "uncontrolled activation of", "activation of the", "of the coagulation", "the coagulation factor", "coagulation factor xii", "xii fxii", "fxii dependent", "dependent kallikrein kinin", "kallikrein kinin system", "kinin system causes", "system causes increased", "causes increased vascular", "increased vascular permeability", "vascular permeability at", "permeability at the", "at the level", "the level of", "level of the", "of the postcapillary", "the postcapillary venule", "postcapillary venule and", "venule and results", "and results in", "results in hereditary", "in hereditary angioedema", "angioedema hae", "bossi f et", "f et al.", "et al. 2009", "2009 kaplan", "kaplan ap 2010", "2010 suffritti", "suffritti c et", "et al. 2014:", "al. 2014: zuraw", "2014: zuraw bl", "zuraw bl &", "bl & christiansen", "& christiansen sc", "christiansen sc 2016", "sc 2016 .", "2016 . hae", ". hae is", "hae is a", "is a rare", "a rare life", "rare life threatening", "life threatening inherited", "threatening inherited edema", "inherited edema disorder", "edema disorder that", "disorder that is", "that is characterized", "is characterized by", "characterized by recurrent", "by recurrent episodes", "recurrent episodes of", "episodes of localized", "of localized edema", "localized edema of", "edema of the", "of the skin", "the skin or", "skin or of", "or of the", "of the mucosa", "the mucosa of", "mucosa of the", "of the gastrointestinal", "the gastrointestinal tract", "gastrointestinal tract or", "tract or upper", "or upper airway.", "upper airway. angioedema", "airway. angioedema initiated", "angioedema initiated by", "initiated by bradykinin", "by bradykinin is", "bradykinin is usually", "is usually associated", "usually associated with", "associated with serping1", "serping1 c1", "inh deficiency.", "thus a", "a major role", "major role of", "role of serping1", "inh is", "is to prevent", "to prevent the", "prevent the development", "the development of", "development of excessive", "of excessive vascular", "excessive vascular permeability.", "vascular permeability. more", "permeability. more rarely", "rarely hae", "hae occurs in", "occurs in individuals", "in individuals with", "individuals with normal", "with normal serping1", "normal serping1 activity", "activity linked", "linked to mutations", "to mutations in", "mutations in other", "in other proteins", "proteins including", "fxii plasminogen", "plasminogen and", "angiopoietin magerl", "magerl m et", "m et al.", "et al. 2017", "2017 zuraw", "zuraw bl 2018", "2018 ivanov", "ivanov i et", "i et al.", "et al. 2019", "al. 2019 .", "2019 . patients", ". patients with", "patients with hae", "with hae are", "hae are heterozygous", "are heterozygous for", "heterozygous for deficiency", "for deficiency of", "deficiency of serping1.the", "of serping1.the disease", "disease therefore", "therefore has", "has an autosomal", "an autosomal dominant", "autosomal dominant inheritance", "dominant inheritance and", "inheritance and may", "and may result", "may result from", "result from lack", "from lack of", "lack of expression", "of expression of", "expression of serping1", "of serping1 from", "serping1 from one", "from one allele", "allele type", "type 1 hae", "hae or", "or from expression", "from expression of", "expression of a", "of a nonfunctional", "a nonfunctional serping1", "nonfunctional serping1 protein", "protein type", "type 2 hae", "2 hae .", "hae . this", ". this classification", "this classification has", "classification has however", "has however been", "however been challenged", "been challenged by", "challenged by observations", "by observations of", "observations of intermediary", "of intermediary hae", "intermediary hae types", "types that", "that can arise", "arise when", "when small amounts", "small amounts of", "amounts of dysfunctional", "of dysfunctional serping1", "dysfunctional serping1 is", "serping1 is present", "is present in", "present in the", "in the blood", "the blood stream", "stream eldering", "eldering e et", "e et al.", "et al. 1995", "1995 verpy", "verpy e et", "1995 madsen", "madsen de et", "de et al.", "et al. 2014", "al. 2014 .", "the reciprocal activation is", "reciprocal activation is initiated", "activation is initiated when", "is initiated when zymogen", "initiated when zymogen factor", "when zymogen factor xii", "factor xii f12", "xii f12 or", "or fxii binds", "fxii binds to", "binds to a negatively", "to a negatively charged", "a negatively charged surface", "charged surface which", "surface which induces", "which induces fxii autoactivation.", "induces fxii autoactivation. activated", "fxii autoactivation. activated fxii", "activated fxii fxiia", "fxiia converts prekallikrein", "converts prekallikrein pk", "pk to kallikrein", "to kallikrein which", "kallikrein which proteolytically", "which proteolytically liberates bradykinin", "proteolytically liberates bradykinin from", "liberates bradykinin from high", "bradykinin from high molecular", "from high molecular weight", "high molecular weight kininogen", "weight kininogen hk", "hk renne", "t 2012 renne", "2012 renne t", "renne t et al.", "t et al. 2012", "al. 2012 maas", "2012 maas c", "maas c et al.", "c et al. 2011", "et al. 2011 .", "al. 2011 . kallikrein", "2011 . kallikrein also", ". kallikrein also activates", "kallikrein also activates fxii", "also activates fxii to", "activates fxii to produce", "fxii to produce more", "to produce more fxiia", "more fxiia initially", "fxiia initially .", "initially . fxiia and", ". fxiia and kallikrein", "fxiia and kallikrein reciprocally", "and kallikrein reciprocally activate", "kallikrein reciprocally activate their", "reciprocally activate their zymogens", "activate their zymogens and", "their zymogens and thus", "zymogens and thus generate", "and thus generate a", "thus generate a positive", "generate a positive feedback", "a positive feedback loop.", "positive feedback loop. in", "feedback loop. in the", "loop. in the presence", "in the presence of", "the presence of sufficient", "presence of sufficient amounts", "of sufficient amounts of", "sufficient amounts of active", "amounts of active enzyme", "active enzyme fxiia", "enzyme fxiia also", "fxiia also generates active", "also generates active factor", "generates active factor xi", "factor xi fxia", "fxia to potentiate", "to potentiate the intrinsic", "potentiate the intrinsic coagulation", "the intrinsic coagulation pathway.", "intrinsic coagulation pathway. all", "coagulation pathway. all of", "pathway. all of these", "all of these enzymatic", "of these enzymatic steps", "these enzymatic steps are", "enzymatic steps are normally", "steps are normally inhibited", "are normally inhibited by", "normally inhibited by c1", "inhibited by c1 esterase", "by c1 esterase inhibitor", "esterase inhibitor c1", "inhibitor c1 inh", "c1 inh encoded", "inh encoded by", "encoded by the serping1", "by the serping1 gene", "the serping1 gene .

              binding", "serping1 gene .

              binding of", "gene .

              binding of the", ".

              binding of the proinflammatory", "of the proinflammatory peptide", "the proinflammatory peptide hormone", "proinflammatory peptide hormone bradykinin", "peptide hormone bradykinin to", "hormone bradykinin to the", "bradykinin to the bradykinin", "to the bradykinin b2", "the bradykinin b2 receptor", "b2 receptor b2r", "b2r activates various", "activates various proinflammatory signaling", "various proinflammatory signaling pathways", "proinflammatory signaling pathways that", "signaling pathways that increase", "pathways that increase vascular", "that increase vascular permeability", "increase vascular permeability and", "vascular permeability and fluid", "permeability and fluid efflux.", "and fluid efflux. an", "fluid efflux. an excessive", "efflux. an excessive formation", "an excessive formation of", "excessive formation of bradykinin", "formation of bradykinin due", "of bradykinin due to", "bradykinin due to uncontrolled", "due to uncontrolled activation", "to uncontrolled activation of", "uncontrolled activation of the", "activation of the coagulation", "of the coagulation factor", "the coagulation factor xii", "factor xii fxii", "fxii dependent kallikrein", "dependent kallikrein kinin system", "kallikrein kinin system causes", "kinin system causes increased", "system causes increased vascular", "causes increased vascular permeability", "increased vascular permeability at", "vascular permeability at the", "permeability at the level", "at the level of", "the level of the", "level of the postcapillary", "of the postcapillary venule", "the postcapillary venule and", "postcapillary venule and results", "venule and results in", "and results in hereditary", "results in hereditary angioedema", "hereditary angioedema hae", "hae bossi", "bossi f et al.", "f et al. 2009", "al. 2009 kaplan", "2009 kaplan ap", "ap 2010 suffritti", "2010 suffritti c", "suffritti c et al.", "c et al. 2014:", "et al. 2014: zuraw", "al. 2014: zuraw bl", "2014: zuraw bl &", "zuraw bl & christiansen", "bl & christiansen sc", "& christiansen sc 2016", "christiansen sc 2016 .", "sc 2016 . hae", "2016 . hae is", ". hae is a", "hae is a rare", "is a rare life", "a rare life threatening", "rare life threatening inherited", "life threatening inherited edema", "threatening inherited edema disorder", "inherited edema disorder that", "edema disorder that is", "disorder that is characterized", "that is characterized by", "is characterized by recurrent", "characterized by recurrent episodes", "by recurrent episodes of", "recurrent episodes of localized", "episodes of localized edema", "of localized edema of", "localized edema of the", "edema of the skin", "of the skin or", "the skin or of", "skin or of the", "or of the mucosa", "of the mucosa of", "the mucosa of the", "mucosa of the gastrointestinal", "of the gastrointestinal tract", "the gastrointestinal tract or", "gastrointestinal tract or upper", "tract or upper airway.", "or upper airway. angioedema", "upper airway. angioedema initiated", "airway. angioedema initiated by", "angioedema initiated by bradykinin", "initiated by bradykinin is", "by bradykinin is usually", "bradykinin is usually associated", "is usually associated with", "usually associated with serping1", "with serping1 c1", "serping1 c1 inh", "c1 inh deficiency.", "inh deficiency. thus", "deficiency. thus a", "thus a major", "a major role of", "major role of serping1", "of serping1 c1", "c1 inh is", "inh is to", "is to prevent the", "to prevent the development", "prevent the development of", "the development of excessive", "development of excessive vascular", "of excessive vascular permeability.", "excessive vascular permeability. more", "vascular permeability. more rarely", "more rarely hae", "rarely hae occurs", "hae occurs in individuals", "occurs in individuals with", "in individuals with normal", "individuals with normal serping1", "with normal serping1 activity", "serping1 activity linked", "activity linked to", "linked to mutations in", "to mutations in other", "mutations in other proteins", "other proteins including", "proteins including fxii", "including fxii plasminogen", "plasminogen and angiopoietin", "and angiopoietin magerl", "angiopoietin magerl m", "magerl m et al.", "m et al. 2017", "al. 2017 zuraw", "2017 zuraw bl", "bl 2018 ivanov", "2018 ivanov i", "ivanov i et al.", "i et al. 2019", "et al. 2019 .", "al. 2019 . patients", "2019 . patients with", ". patients with hae", "patients with hae are", "with hae are heterozygous", "hae are heterozygous for", "are heterozygous for deficiency", "heterozygous for deficiency of", "for deficiency of serping1.the", "deficiency of serping1.the disease", "serping1.the disease therefore", "therefore has an", "has an autosomal dominant", "an autosomal dominant inheritance", "autosomal dominant inheritance and", "dominant inheritance and may", "inheritance and may result", "and may result from", "may result from lack", "result from lack of", "from lack of expression", "lack of expression of", "of expression of serping1", "expression of serping1 from", "of serping1 from one", "serping1 from one allele", "one allele type", "allele type 1", "1 hae or", "hae or from", "or from expression of", "from expression of a", "expression of a nonfunctional", "of a nonfunctional serping1", "a nonfunctional serping1 protein", "serping1 protein type", "protein type 2", "type 2 hae .", "2 hae . this", "hae . this classification", ". this classification has", "this classification has however", "classification has however been", "has however been challenged", "however been challenged by", "been challenged by observations", "challenged by observations of", "by observations of intermediary", "observations of intermediary hae", "of intermediary hae types", "hae types that", "types that can", "can arise when", "arise when small", "when small amounts of", "small amounts of dysfunctional", "amounts of dysfunctional serping1", "of dysfunctional serping1 is", "dysfunctional serping1 is present", "serping1 is present in", "is present in the", "present in the blood", "in the blood stream", "blood stream eldering", "stream eldering e", "eldering e et al.", "e et al. 1995", "al. 1995 verpy", "1995 verpy e", "verpy e et al.", "al. 1995 madsen", "1995 madsen de", "madsen de et al.", "de et al. 2014", "et al. 2014 .", "the reciprocal activation is initiated", "reciprocal activation is initiated when", "activation is initiated when zymogen", "is initiated when zymogen factor", "initiated when zymogen factor xii", "zymogen factor xii f12", "factor xii f12 or", "xii f12 or fxii", "f12 or fxii binds", "or fxii binds to", "fxii binds to a", "binds to a negatively charged", "to a negatively charged surface", "negatively charged surface which", "charged surface which induces", "surface which induces fxii", "which induces fxii autoactivation. activated", "induces fxii autoactivation. activated fxii", "autoactivation. activated fxii fxiia", "fxii fxiia converts", "prekallikrein pk to", "to kallikrein which proteolytically", "kallikrein which proteolytically liberates", "which proteolytically liberates bradykinin from", "proteolytically liberates bradykinin from high", "liberates bradykinin from high molecular", "bradykinin from high molecular weight", "from high molecular weight kininogen", "molecular weight kininogen hk", "hk renne t", "renne t 2012 renne", "t 2012 renne t", "2012 renne t et", "renne t et al. 2012", "et al. 2012 maas", "al. 2012 maas c", "2012 maas c et", "maas c et al. 2011", "c et al. 2011 .", "et al. 2011 . kallikrein", "al. 2011 . kallikrein also", "2011 . kallikrein also activates", ". kallikrein also activates fxii", "kallikrein also activates fxii to", "also activates fxii to produce", "activates fxii to produce more", "fxii to produce more fxiia", "produce more fxiia initially", "more fxiia initially .", "fxiia initially . fxiia", "initially . fxiia and kallikrein", ". fxiia and kallikrein reciprocally", "fxiia and kallikrein reciprocally activate", "and kallikrein reciprocally activate their", "kallikrein reciprocally activate their zymogens", "reciprocally activate their zymogens and", "activate their zymogens and thus", "their zymogens and thus generate", "zymogens and thus generate a", "and thus generate a positive", "thus generate a positive feedback", "generate a positive feedback loop.", "a positive feedback loop. in", "positive feedback loop. in the", "feedback loop. in the presence", "loop. in the presence of", "in the presence of sufficient", "the presence of sufficient amounts", "presence of sufficient amounts of", "of sufficient amounts of active", "sufficient amounts of active enzyme", "of active enzyme fxiia", "active enzyme fxiia also", "enzyme fxiia also generates", "fxiia also generates active factor", "also generates active factor xi", "active factor xi fxia", "xi fxia to", "fxia to potentiate the", "to potentiate the intrinsic coagulation", "potentiate the intrinsic coagulation pathway.", "the intrinsic coagulation pathway. all", "intrinsic coagulation pathway. all of", "coagulation pathway. all of these", "pathway. all of these enzymatic", "all of these enzymatic steps", "of these enzymatic steps are", "these enzymatic steps are normally", "enzymatic steps are normally inhibited", "steps are normally inhibited by", "are normally inhibited by c1", "normally inhibited by c1 esterase", "inhibited by c1 esterase inhibitor", "c1 esterase inhibitor c1", "esterase inhibitor c1 inh", "c1 inh encoded by", "inh encoded by the", "encoded by the serping1 gene", "by the serping1 gene .

              binding", "the serping1 gene .

              binding of", "serping1 gene .

              binding of the", "gene .

              binding of the proinflammatory", ".

              binding of the proinflammatory peptide", "of the proinflammatory peptide hormone", "the proinflammatory peptide hormone bradykinin", "proinflammatory peptide hormone bradykinin to", "peptide hormone bradykinin to the", "hormone bradykinin to the bradykinin", "bradykinin to the bradykinin b2", "to the bradykinin b2 receptor", "bradykinin b2 receptor b2r", "receptor b2r activates", "b2r activates various proinflammatory", "activates various proinflammatory signaling pathways", "various proinflammatory signaling pathways that", "proinflammatory signaling pathways that increase", "signaling pathways that increase vascular", "pathways that increase vascular permeability", "that increase vascular permeability and", "increase vascular permeability and fluid", "vascular permeability and fluid efflux.", "permeability and fluid efflux. an", "and fluid efflux. an excessive", "fluid efflux. an excessive formation", "efflux. an excessive formation of", "an excessive formation of bradykinin", "excessive formation of bradykinin due", "formation of bradykinin due to", "of bradykinin due to uncontrolled", "bradykinin due to uncontrolled activation", "due to uncontrolled activation of", "to uncontrolled activation of the", "uncontrolled activation of the coagulation", "activation of the coagulation factor", "of the coagulation factor xii", "coagulation factor xii fxii", "xii fxii dependent", "fxii dependent kallikrein kinin", "dependent kallikrein kinin system causes", "kallikrein kinin system causes increased", "kinin system causes increased vascular", "system causes increased vascular permeability", "causes increased vascular permeability at", "increased vascular permeability at the", "vascular permeability at the level", "permeability at the level of", "at the level of the", "the level of the postcapillary", "level of the postcapillary venule", "of the postcapillary venule and", "the postcapillary venule and results", "postcapillary venule and results in", "venule and results in hereditary", "and results in hereditary angioedema", "in hereditary angioedema hae", "hae bossi f", "bossi f et al. 2009", "et al. 2009 kaplan", "al. 2009 kaplan ap", "2009 kaplan ap 2010", "kaplan ap 2010 suffritti", "ap 2010 suffritti c", "2010 suffritti c et", "suffritti c et al. 2014:", "c et al. 2014: zuraw", "et al. 2014: zuraw bl", "al. 2014: zuraw bl &", "2014: zuraw bl & christiansen", "zuraw bl & christiansen sc", "bl & christiansen sc 2016", "& christiansen sc 2016 .", "christiansen sc 2016 . hae", "sc 2016 . hae is", "2016 . hae is a", ". hae is a rare", "hae is a rare life", "is a rare life threatening", "a rare life threatening inherited", "rare life threatening inherited edema", "life threatening inherited edema disorder", "threatening inherited edema disorder that", "inherited edema disorder that is", "edema disorder that is characterized", "disorder that is characterized by", "that is characterized by recurrent", "is characterized by recurrent episodes", "characterized by recurrent episodes of", "by recurrent episodes of localized", "recurrent episodes of localized edema", "episodes of localized edema of", "of localized edema of the", "localized edema of the skin", "edema of the skin or", "of the skin or of", "the skin or of the", "skin or of the mucosa", "or of the mucosa of", "of the mucosa of the", "the mucosa of the gastrointestinal", "mucosa of the gastrointestinal tract", "of the gastrointestinal tract or", "the gastrointestinal tract or upper", "gastrointestinal tract or upper airway.", "tract or upper airway. angioedema", "or upper airway. angioedema initiated", "upper airway. angioedema initiated by", "airway. angioedema initiated by bradykinin", "angioedema initiated by bradykinin is", "initiated by bradykinin is usually", "by bradykinin is usually associated", "bradykinin is usually associated with", "is usually associated with serping1", "associated with serping1 c1", "with serping1 c1 inh", "c1 inh deficiency. thus", "deficiency. thus a major", "thus a major role", "a major role of serping1", "role of serping1 c1", "of serping1 c1 inh", "c1 inh is to", "inh is to prevent", "is to prevent the development", "to prevent the development of", "prevent the development of excessive", "the development of excessive vascular", "development of excessive vascular permeability.", "of excessive vascular permeability. more", "excessive vascular permeability. more rarely", "permeability. more rarely hae", "more rarely hae occurs", "rarely hae occurs in", "hae occurs in individuals with", "occurs in individuals with normal", "in individuals with normal serping1", "individuals with normal serping1 activity", "normal serping1 activity linked", "serping1 activity linked to", "activity linked to mutations", "linked to mutations in other", "to mutations in other proteins", "in other proteins including", "other proteins including fxii", "fxii plasminogen and", "and angiopoietin magerl m", "angiopoietin magerl m et", "magerl m et al. 2017", "et al. 2017 zuraw", "al. 2017 zuraw bl", "2017 zuraw bl 2018", "zuraw bl 2018 ivanov", "bl 2018 ivanov i", "2018 ivanov i et", "ivanov i et al. 2019", "i et al. 2019 .", "et al. 2019 . patients", "al. 2019 . patients with", "2019 . patients with hae", ". patients with hae are", "patients with hae are heterozygous", "with hae are heterozygous for", "hae are heterozygous for deficiency", "are heterozygous for deficiency of", "heterozygous for deficiency of serping1.the", "for deficiency of serping1.the disease", "of serping1.the disease therefore", "disease therefore has", "therefore has an autosomal", "has an autosomal dominant inheritance", "an autosomal dominant inheritance and", "autosomal dominant inheritance and may", "dominant inheritance and may result", "inheritance and may result from", "and may result from lack", "may result from lack of", "result from lack of expression", "from lack of expression of", "lack of expression of serping1", "of expression of serping1 from", "expression of serping1 from one", "of serping1 from one allele", "from one allele type", "one allele type 1", "allele type 1 hae", "type 1 hae or", "1 hae or from", "hae or from expression", "or from expression of a", "from expression of a nonfunctional", "expression of a nonfunctional serping1", "of a nonfunctional serping1 protein", "nonfunctional serping1 protein type", "serping1 protein type 2", "protein type 2 hae", "type 2 hae . this", "2 hae . this classification", "hae . this classification has", ". this classification has however", "this classification has however been", "classification has however been challenged", "has however been challenged by", "however been challenged by observations", "been challenged by observations of", "challenged by observations of intermediary", "by observations of intermediary hae", "observations of intermediary hae types", "intermediary hae types that", "hae types that can", "types that can arise", "that can arise when", "can arise when small", "arise when small amounts", "when small amounts of dysfunctional", "small amounts of dysfunctional serping1", "amounts of dysfunctional serping1 is", "of dysfunctional serping1 is present", "dysfunctional serping1 is present in", "serping1 is present in the", "is present in the blood", "present in the blood stream", "the blood stream eldering", "blood stream eldering e", "stream eldering e et", "eldering e et al. 1995", "et al. 1995 verpy", "al. 1995 verpy e", "1995 verpy e et", "verpy e et al. 1995", "et al. 1995 madsen", "al. 1995 madsen de", "1995 madsen de et", "madsen de et al. 2014", "de et al. 2014 ." ] }, { "record_id": "GLY_000594_1_1982", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9665348", "r hsa", "hsa 9665348", "r hsa 9665348" ] }, { "record_id": "GLY_000594_1_1982", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by erbb2", "erbb2 ecd", "ecd mutants", "signaling by erbb2", "by erbb2 ecd", "erbb2 ecd mutants", "signaling by erbb2 ecd", "by erbb2 ecd mutants", "signaling by erbb2 ecd mutants", "erbb2 extracellular", "extracellular domain", "mutants harbor", "harbor missense", "missense mutations", "mutations that", "that lead", "lead to", "to substitutions", "substitutions of", "of amino", "amino acid", "acid residues", "residues in", "in the", "the heterodimerization", "heterodimerization arm", "arm contact", "contact surface", "involved in", "in formation", "formation of", "of erbb2", "erbb2 heterodimers.", "heterodimers. the", "the functionally", "functionally studied", "studied erbb2", "erbb2 g309a", "bose et", "et al.", "al. 2013", "erbb2 g309e", "greulich et", "al. 2012", "and erbb2", "erbb2 s310f", "seem to", "to preferntially", "preferntially heterodimerize", "heterodimerize with", "with egfr.", "egfr. heterodimerization", "heterodimerization of", "g309e involves", "involves formation", "of disulfide", "disulfide bonds", "2012 .", ". erbb2", "s310f shows", "shows stronger", "stronger activation", "activation of", "of downstream", "downstream signaling", "signaling than", "than erbb2", "g309a and", "and is", "is hyperphosphorylated", "hyperphosphorylated on", "on tyrosine", "tyrosine residues", "the c", "c tail", "while the", "tail phosphorylation", "phosphorylation of", "is comparable", "comparable to", "to the", "the wild", "wild type", "type erbb2.
              ", "erbb2.
              ras", "ras signaling", "signaling and", "and plcgamma1", "plcgamma1 signaling", "signaling are", "are activated", "activated dowsntream", "dowsntream of", "of all", "all three", "three erbb2", "as evidenced", "evidenced by", "by activating", "activating phosphorylation", "phosphorylation on", "on erks", "mapk1 and", "and mapk3", "and plcg1", "respectively. erbb2", "g309e and", "s310f also", "also activate", "activate pi3k/akt", "pi3k/akt signaling", "demonstrated by", "of akt1", ". activation", "of pi3k/akt", "signaling downstream", "downstream of", "g309a has", "has not", "not been", "been tested.", "tested. signaling", "erbb2 s310y", "s310y has", "has been", "been poorly", "poorly characterized", "characterized and", "and it", "it is", "is annotated", "annotated as", "as a", "a candidate.", "candidate. many", "many regulators", "regulators of", "of cell", "cell migration", "migration show", "show increased", "increased phosphorylation", "phosphorylation in", "in cells", "cells expressing", "expressing erbb2", "2012 .
              comapred", ".
              comapred with", "with the", "type erbb2", "s310f and", "s310y are", "are more", "more sensitive", "sensitive to", "the erbb2", "erbb2 directed", "directed therapeutic", "therapeutic antibody", "antibody trastuzumab", "and to", "to tyrosine", "tyrosine kinase", "kinase inhibitors", "inhibitors lapatinib", "neratinib and", "and afatinib", "g309a was", "was also", "also responsive", "responsive to", "to trastuzumab", "lapatinib and", "and neratinib", "2013 .", "erbb2 extracellular domain", "domain ecd", "mutants harbor missense", "harbor missense mutations", "missense mutations that", "mutations that lead", "that lead to", "lead to substitutions", "to substitutions of", "substitutions of amino", "of amino acid", "amino acid residues", "acid residues in", "residues in the", "in the heterodimerization", "the heterodimerization arm", "heterodimerization arm contact", "arm contact surface", "surface involved", "involved in formation", "in formation of", "formation of erbb2", "of erbb2 heterodimers.", "erbb2 heterodimers. the", "heterodimers. the functionally", "the functionally studied", "functionally studied erbb2", "studied erbb2 ecd", "mutants erbb2", "g309a bose", "bose et al.", "et al. 2013", "g309e greulich", "greulich et al.", "et al. 2012", "2012 and", "and erbb2 s310f", "s310f greulich", "2012 seem", "seem to preferntially", "to preferntially heterodimerize", "preferntially heterodimerize with", "heterodimerize with egfr.", "with egfr. heterodimerization", "egfr. heterodimerization of", "heterodimerization of erbb2", "of erbb2 g309e", "erbb2 g309e involves", "g309e involves formation", "involves formation of", "formation of disulfide", "of disulfide bonds", "bonds greulich", "al. 2012 .", "2012 . erbb2", ". erbb2 s310f", "erbb2 s310f shows", "s310f shows stronger", "shows stronger activation", "stronger activation of", "activation of downstream", "of downstream signaling", "downstream signaling than", "signaling than erbb2", "than erbb2 g309a", "erbb2 g309a and", "g309a and erbb2", "and erbb2 g309e", "and is hyperphosphorylated", "is hyperphosphorylated on", "hyperphosphorylated on tyrosine", "on tyrosine residues", "tyrosine residues in", "in the c", "the c tail", "tail greulich", "while the c", "c tail phosphorylation", "tail phosphorylation of", "phosphorylation of erbb2", "of erbb2 g309a", "2013 and", "2012 is", "is comparable to", "comparable to the", "to the wild", "the wild type", "wild type erbb2.
              ", "type erbb2.
              ras", "erbb2.
              ras signaling", "ras signaling and", "signaling and plcgamma1", "and plcgamma1 signaling", "plcgamma1 signaling are", "signaling are activated", "are activated dowsntream", "activated dowsntream of", "dowsntream of all", "of all three", "all three erbb2", "three erbb2 ecd", "as evidenced by", "evidenced by activating", "by activating phosphorylation", "activating phosphorylation on", "phosphorylation on erks", "erks mapk1", "mapk1 and mapk3", "mapk3 and", "plcg1 respectively.", "respectively. erbb2 g309e", "erbb2 g309e and", "g309e and erbb2", "erbb2 s310f also", "s310f also activate", "also activate pi3k/akt", "activate pi3k/akt signaling", "signaling demonstrated", "demonstrated by activating", "activating phosphorylation of", "phosphorylation of akt1", "akt1 greulich", "2012 . activation", ". activation of", "activation of pi3k/akt", "of pi3k/akt signaling", "pi3k/akt signaling downstream", "signaling downstream of", "downstream of erbb2", "erbb2 g309a has", "g309a has not", "has not been", "not been tested.", "been tested. signaling", "tested. signaling downstream", "of erbb2 s310y", "erbb2 s310y has", "s310y has been", "has been poorly", "been poorly characterized", "poorly characterized and", "characterized and it", "and it is", "it is annotated", "is annotated as", "annotated as a", "as a candidate.", "a candidate. many", "candidate. many regulators", "many regulators of", "regulators of cell", "of cell migration", "cell migration show", "migration show increased", "show increased phosphorylation", "increased phosphorylation in", "phosphorylation in cells", "in cells expressing", "cells expressing erbb2", "expressing erbb2 g309e", "al. 2012 .
              comapred", "2012 .
              comapred with", ".
              comapred with the", "with the wild", "wild type erbb2", "erbb2 erbb2", "g309e erbb2", "erbb2 s310f and", "s310f and erbb2", "and erbb2 s310y", "erbb2 s310y are", "s310y are more", "are more sensitive", "more sensitive to", "sensitive to the", "to the erbb2", "the erbb2 directed", "erbb2 directed therapeutic", "directed therapeutic antibody", "therapeutic antibody trastuzumab", "trastuzumab herceptin", "herceptin and", "and to tyrosine", "to tyrosine kinase", "tyrosine kinase inhibitors", "kinase inhibitors lapatinib", "lapatinib neratinib", "neratinib and afatinib", "afatinib greulich", ". erbb2 g309a", "erbb2 g309a was", "g309a was also", "was also responsive", "also responsive to", "responsive to trastuzumab", "trastuzumab lapatinib", "lapatinib and neratinib", "neratinib bose", "al. 2013 .", "extracellular domain ecd", "ecd mutants harbor", "mutants harbor missense mutations", "harbor missense mutations that", "missense mutations that lead", "mutations that lead to", "that lead to substitutions", "lead to substitutions of", "to substitutions of amino", "substitutions of amino acid", "of amino acid residues", "amino acid residues in", "acid residues in the", "residues in the heterodimerization", "in the heterodimerization arm", "the heterodimerization arm contact", "heterodimerization arm contact surface", "contact surface involved", "surface involved in", "involved in formation of", "in formation of erbb2", "formation of erbb2 heterodimers.", "of erbb2 heterodimers. the", "erbb2 heterodimers. the functionally", "heterodimers. the functionally studied", "the functionally studied erbb2", "functionally studied erbb2 ecd", "studied erbb2 ecd mutants", "ecd mutants erbb2", "mutants erbb2 g309a", "erbb2 g309a bose", "g309a bose et", "bose et al. 2013", "2013 erbb2", "erbb2 g309e greulich", "g309e greulich et", "greulich et al. 2012", "al. 2012 and", "2012 and erbb2", "erbb2 s310f greulich", "s310f greulich et", "al. 2012 seem", "2012 seem to", "seem to preferntially heterodimerize", "to preferntially heterodimerize with", "preferntially heterodimerize with egfr.", "heterodimerize with egfr. heterodimerization", "with egfr. heterodimerization of", "egfr. heterodimerization of erbb2", "heterodimerization of erbb2 g309e", "of erbb2 g309e involves", "erbb2 g309e involves formation", "g309e involves formation of", "involves formation of disulfide", "formation of disulfide bonds", "disulfide bonds greulich", "bonds greulich et", "et al. 2012 .", "al. 2012 . erbb2", "2012 . erbb2 s310f", ". erbb2 s310f shows", "erbb2 s310f shows stronger", "s310f shows stronger activation", "shows stronger activation of", "stronger activation of downstream", "activation of downstream signaling", "of downstream signaling than", "downstream signaling than erbb2", "signaling than erbb2 g309a", "than erbb2 g309a and", "erbb2 g309a and erbb2", "g309a and erbb2 g309e", "g309e and is", "and is hyperphosphorylated on", "is hyperphosphorylated on tyrosine", "hyperphosphorylated on tyrosine residues", "on tyrosine residues in", "tyrosine residues in the", "residues in the c", "in the c tail", "c tail greulich", "tail greulich et", "2012 while", "while the c tail", "the c tail phosphorylation", "c tail phosphorylation of", "tail phosphorylation of erbb2", "phosphorylation of erbb2 g309a", "al. 2013 and", "2013 and erbb2", "al. 2012 is", "2012 is comparable", "is comparable to the", "comparable to the wild", "to the wild type", "the wild type erbb2.
              ", "wild type erbb2.
              ras", "type erbb2.
              ras signaling", "erbb2.
              ras signaling and", "ras signaling and plcgamma1", "signaling and plcgamma1 signaling", "and plcgamma1 signaling are", "plcgamma1 signaling are activated", "signaling are activated dowsntream", "are activated dowsntream of", "activated dowsntream of all", "dowsntream of all three", "of all three erbb2", "all three erbb2 ecd", "three erbb2 ecd mutants", "2012 as", "as evidenced by activating", "evidenced by activating phosphorylation", "by activating phosphorylation on", "activating phosphorylation on erks", "on erks mapk1", "erks mapk1 and", "and mapk3 and", "mapk3 and plcg1", "and plcg1 respectively.", "plcg1 respectively. erbb2", "respectively. erbb2 g309e and", "erbb2 g309e and erbb2", "g309e and erbb2 s310f", "and erbb2 s310f also", "erbb2 s310f also activate", "s310f also activate pi3k/akt", "also activate pi3k/akt signaling", "pi3k/akt signaling demonstrated", "signaling demonstrated by", "demonstrated by activating phosphorylation", "by activating phosphorylation of", "activating phosphorylation of akt1", "of akt1 greulich", "akt1 greulich et", "al. 2012 . activation", "2012 . activation of", ". activation of pi3k/akt", "activation of pi3k/akt signaling", "of pi3k/akt signaling downstream", "pi3k/akt signaling downstream of", "signaling downstream of erbb2", "downstream of erbb2 g309a", "of erbb2 g309a has", "erbb2 g309a has not", "g309a has not been", "has not been tested.", "not been tested. signaling", "been tested. signaling downstream", "tested. signaling downstream of", "downstream of erbb2 s310y", "of erbb2 s310y has", "erbb2 s310y has been", "s310y has been poorly", "has been poorly characterized", "been poorly characterized and", "poorly characterized and it", "characterized and it is", "and it is annotated", "it is annotated as", "is annotated as a", "annotated as a candidate.", "as a candidate. many", "a candidate. many regulators", "candidate. many regulators of", "many regulators of cell", "regulators of cell migration", "of cell migration show", "cell migration show increased", "migration show increased phosphorylation", "show increased phosphorylation in", "increased phosphorylation in cells", "phosphorylation in cells expressing", "in cells expressing erbb2", "cells expressing erbb2 g309e", "expressing erbb2 g309e and", "et al. 2012 .
              comapred", "al. 2012 .
              comapred with", "2012 .
              comapred with the", ".
              comapred with the wild", "with the wild type", "the wild type erbb2", "type erbb2 erbb2", "erbb2 erbb2 g309e", "erbb2 g309e erbb2", "g309e erbb2 s310f", "erbb2 s310f and erbb2", "s310f and erbb2 s310y", "and erbb2 s310y are", "erbb2 s310y are more", "s310y are more sensitive", "are more sensitive to", "more sensitive to the", "sensitive to the erbb2", "to the erbb2 directed", "the erbb2 directed therapeutic", "erbb2 directed therapeutic antibody", "directed therapeutic antibody trastuzumab", "antibody trastuzumab herceptin", "herceptin and to", "and to tyrosine kinase", "to tyrosine kinase inhibitors", "tyrosine kinase inhibitors lapatinib", "inhibitors lapatinib neratinib", "lapatinib neratinib and", "and afatinib greulich", "afatinib greulich et", "2012 . erbb2 g309a", ". erbb2 g309a was", "erbb2 g309a was also", "g309a was also responsive", "was also responsive to", "also responsive to trastuzumab", "to trastuzumab lapatinib", "trastuzumab lapatinib and", "and neratinib bose", "neratinib bose et", "et al. 2013 .", "erbb2 extracellular domain ecd", "domain ecd mutants", "ecd mutants harbor missense", "mutants harbor missense mutations that", "harbor missense mutations that lead", "missense mutations that lead to", "mutations that lead to substitutions", "that lead to substitutions of", "lead to substitutions of amino", "to substitutions of amino acid", "substitutions of amino acid residues", "of amino acid residues in", "amino acid residues in the", "acid residues in the heterodimerization", "residues in the heterodimerization arm", "in the heterodimerization arm contact", "the heterodimerization arm contact surface", "arm contact surface involved", "contact surface involved in", "surface involved in formation", "involved in formation of erbb2", "in formation of erbb2 heterodimers.", "formation of erbb2 heterodimers. the", "of erbb2 heterodimers. the functionally", "erbb2 heterodimers. the functionally studied", "heterodimers. the functionally studied erbb2", "the functionally studied erbb2 ecd", "functionally studied erbb2 ecd mutants", "erbb2 ecd mutants erbb2", "ecd mutants erbb2 g309a", "erbb2 g309a bose et", "g309a bose et al.", "al. 2013 erbb2", "2013 erbb2 g309e", "erbb2 g309e greulich et", "g309e greulich et al.", "et al. 2012 and", "al. 2012 and erbb2", "2012 and erbb2 s310f", "and erbb2 s310f greulich", "erbb2 s310f greulich et", "s310f greulich et al.", "et al. 2012 seem", "al. 2012 seem to", "2012 seem to preferntially", "seem to preferntially heterodimerize with", "to preferntially heterodimerize with egfr.", "preferntially heterodimerize with egfr. heterodimerization", "heterodimerize with egfr. heterodimerization of", "with egfr. heterodimerization of erbb2", "egfr. heterodimerization of erbb2 g309e", "heterodimerization of erbb2 g309e involves", "of erbb2 g309e involves formation", "erbb2 g309e involves formation of", "g309e involves formation of disulfide", "involves formation of disulfide bonds", "of disulfide bonds greulich", "disulfide bonds greulich et", "bonds greulich et al.", "greulich et al. 2012 .", "et al. 2012 . erbb2", "al. 2012 . erbb2 s310f", "2012 . erbb2 s310f shows", ". erbb2 s310f shows stronger", "erbb2 s310f shows stronger activation", "s310f shows stronger activation of", "shows stronger activation of downstream", "stronger activation of downstream signaling", "activation of downstream signaling than", "of downstream signaling than erbb2", "downstream signaling than erbb2 g309a", "signaling than erbb2 g309a and", "than erbb2 g309a and erbb2", "erbb2 g309a and erbb2 g309e", "and erbb2 g309e and", "erbb2 g309e and is", "g309e and is hyperphosphorylated", "and is hyperphosphorylated on tyrosine", "is hyperphosphorylated on tyrosine residues", "hyperphosphorylated on tyrosine residues in", "on tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "the c tail greulich", "c tail greulich et", "tail greulich et al.", "al. 2012 while", "2012 while the", "while the c tail phosphorylation", "the c tail phosphorylation of", "c tail phosphorylation of erbb2", "tail phosphorylation of erbb2 g309a", "of erbb2 g309a bose", "et al. 2013 and", "al. 2013 and erbb2", "2013 and erbb2 g309e", "and erbb2 g309e greulich", "et al. 2012 is", "al. 2012 is comparable", "2012 is comparable to", "is comparable to the wild", "comparable to the wild type", "to the wild type erbb2.
              ", "the wild type erbb2.
              ras", "wild type erbb2.
              ras signaling", "type erbb2.
              ras signaling and", "erbb2.
              ras signaling and plcgamma1", "ras signaling and plcgamma1 signaling", "signaling and plcgamma1 signaling are", "and plcgamma1 signaling are activated", "plcgamma1 signaling are activated dowsntream", "signaling are activated dowsntream of", "are activated dowsntream of all", "activated dowsntream of all three", "dowsntream of all three erbb2", "of all three erbb2 ecd", "all three erbb2 ecd mutants", "al. 2012 as", "2012 as evidenced", "as evidenced by activating phosphorylation", "evidenced by activating phosphorylation on", "by activating phosphorylation on erks", "phosphorylation on erks mapk1", "on erks mapk1 and", "erks mapk1 and mapk3", "mapk1 and mapk3 and", "and mapk3 and plcg1", "and plcg1 respectively. erbb2", "plcg1 respectively. erbb2 g309e", "respectively. erbb2 g309e and erbb2", "erbb2 g309e and erbb2 s310f", "g309e and erbb2 s310f also", "and erbb2 s310f also activate", "erbb2 s310f also activate pi3k/akt", "s310f also activate pi3k/akt signaling", "activate pi3k/akt signaling demonstrated", "pi3k/akt signaling demonstrated by", "signaling demonstrated by activating", "demonstrated by activating phosphorylation of", "by activating phosphorylation of akt1", "phosphorylation of akt1 greulich", "of akt1 greulich et", "akt1 greulich et al.", "et al. 2012 . activation", "al. 2012 . activation of", "2012 . activation of pi3k/akt", ". activation of pi3k/akt signaling", "activation of pi3k/akt signaling downstream", "of pi3k/akt signaling downstream of", "pi3k/akt signaling downstream of erbb2", "signaling downstream of erbb2 g309a", "downstream of erbb2 g309a has", "of erbb2 g309a has not", "erbb2 g309a has not been", "g309a has not been tested.", "has not been tested. signaling", "not been tested. signaling downstream", "been tested. signaling downstream of", "tested. signaling downstream of erbb2", "signaling downstream of erbb2 s310y", "downstream of erbb2 s310y has", "of erbb2 s310y has been", "erbb2 s310y has been poorly", "s310y has been poorly characterized", "has been poorly characterized and", "been poorly characterized and it", "poorly characterized and it is", "characterized and it is annotated", "and it is annotated as", "it is annotated as a", "is annotated as a candidate.", "annotated as a candidate. many", "as a candidate. many regulators", "a candidate. many regulators of", "candidate. many regulators of cell", "many regulators of cell migration", "regulators of cell migration show", "of cell migration show increased", "cell migration show increased phosphorylation", "migration show increased phosphorylation in", "show increased phosphorylation in cells", "increased phosphorylation in cells expressing", "phosphorylation in cells expressing erbb2", "in cells expressing erbb2 g309e", "cells expressing erbb2 g309e and", "expressing erbb2 g309e and erbb2", "greulich et al. 2012 .
              comapred", "et al. 2012 .
              comapred with", "al. 2012 .
              comapred with the", "2012 .
              comapred with the wild", ".
              comapred with the wild type", "with the wild type erbb2", "wild type erbb2 erbb2", "type erbb2 erbb2 g309e", "erbb2 g309e erbb2 s310f", "g309e erbb2 s310f and", "erbb2 s310f and erbb2 s310y", "s310f and erbb2 s310y are", "and erbb2 s310y are more", "erbb2 s310y are more sensitive", "s310y are more sensitive to", "are more sensitive to the", "more sensitive to the erbb2", "sensitive to the erbb2 directed", "to the erbb2 directed therapeutic", "the erbb2 directed therapeutic antibody", "erbb2 directed therapeutic antibody trastuzumab", "therapeutic antibody trastuzumab herceptin", "trastuzumab herceptin and", "herceptin and to tyrosine", "and to tyrosine kinase inhibitors", "to tyrosine kinase inhibitors lapatinib", "kinase inhibitors lapatinib neratinib", "inhibitors lapatinib neratinib and", "lapatinib neratinib and afatinib", "neratinib and afatinib greulich", "and afatinib greulich et", "afatinib greulich et al.", "al. 2012 . erbb2 g309a", "2012 . erbb2 g309a was", ". erbb2 g309a was also", "erbb2 g309a was also responsive", "g309a was also responsive to", "was also responsive to trastuzumab", "responsive to trastuzumab lapatinib", "to trastuzumab lapatinib and", "trastuzumab lapatinib and neratinib", "lapatinib and neratinib bose", "and neratinib bose et", "neratinib bose et al.", "bose et al. 2013 ." ] }, { "record_id": "GLY_000594_1_1983", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9672383", "r hsa", "hsa 9672383", "r hsa 9672383" ] }, { "record_id": "GLY_000594_1_1983", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective factor", "factor ix", "ix causes", "causes thrombophilia", "defective factor ix", "factor ix causes", "ix causes thrombophilia", "defective factor ix causes", "factor ix causes thrombophilia", "defective factor ix causes thrombophilia", "in healthy", "healthy individuals", "individuals factor", "factor ixa", "in a", "a complex", "complex with", "with factor", "factor viiia", "viiia on", "on the", "the surfaces", "surfaces of", "of activated", "activated platelets", "catalyzes the", "the formation", "formation of", "activated factor", "factor x", "x with", "with high", "high efficiency.", "efficiency. a", "a substitution", "substitution of", "of leucine", "leucine for", "for arginine", "arginine at", "at residue", "residue 384", "384 in", "in fix", "fix r384l", "also know", "know as", "as fix", "fix padua", "is a", "a gain", "gain of", "of function", "function mutation", "mutation that", "that resulted", "resulted in", "in elevated", "elevated fix", "fix clotting", "clotting activity", "activity in", "a patient", "patient with", "with venous", "venous thrombosis", "simioni p", "p et", "et al.", "al. 2009", "2009 .", "in healthy individuals", "healthy individuals factor", "individuals factor ixa", "ixa fixa", "in a complex", "a complex with", "complex with factor", "with factor viiia", "factor viiia on", "viiia on the", "on the surfaces", "the surfaces of", "surfaces of activated", "of activated platelets", "platelets catalyzes", "catalyzes the formation", "the formation of", "formation of activated", "of activated factor", "activated factor x", "factor x with", "x with high", "with high efficiency.", "high efficiency. a", "efficiency. a substitution", "a substitution of", "substitution of leucine", "of leucine for", "leucine for arginine", "for arginine at", "arginine at residue", "at residue 384", "residue 384 in", "384 in fix", "fix fix", "r384l also", "also know as", "know as fix", "as fix padua", "padua is", "is a gain", "a gain of", "gain of function", "of function mutation", "function mutation that", "mutation that resulted", "that resulted in", "resulted in elevated", "in elevated fix", "elevated fix clotting", "fix clotting activity", "clotting activity in", "activity in a", "in a patient", "a patient with", "patient with venous", "with venous thrombosis", "thrombosis simioni", "simioni p et", "p et al.", "et al. 2009", "al. 2009 .", "in healthy individuals factor", "healthy individuals factor ixa", "factor ixa fixa", "fixa in", "in a complex with", "a complex with factor", "complex with factor viiia", "with factor viiia on", "factor viiia on the", "viiia on the surfaces", "on the surfaces of", "the surfaces of activated", "surfaces of activated platelets", "activated platelets catalyzes", "platelets catalyzes the", "catalyzes the formation of", "the formation of activated", "formation of activated factor", "of activated factor x", "activated factor x with", "factor x with high", "x with high efficiency.", "with high efficiency. a", "high efficiency. a substitution", "efficiency. a substitution of", "a substitution of leucine", "substitution of leucine for", "of leucine for arginine", "leucine for arginine at", "for arginine at residue", "arginine at residue 384", "at residue 384 in", "residue 384 in fix", "in fix fix", "fix fix r384l", "fix r384l also", "r384l also know", "also know as fix", "know as fix padua", "fix padua is", "padua is a", "is a gain of", "a gain of function", "gain of function mutation", "of function mutation that", "function mutation that resulted", "mutation that resulted in", "that resulted in elevated", "resulted in elevated fix", "in elevated fix clotting", "elevated fix clotting activity", "fix clotting activity in", "clotting activity in a", "activity in a patient", "in a patient with", "a patient with venous", "patient with venous thrombosis", "venous thrombosis simioni", "thrombosis simioni p", "simioni p et al.", "p et al. 2009", "et al. 2009 .", "in healthy individuals factor ixa", "individuals factor ixa fixa", "fixa in a", "in a complex with factor", "a complex with factor viiia", "complex with factor viiia on", "with factor viiia on the", "factor viiia on the surfaces", "viiia on the surfaces of", "on the surfaces of activated", "the surfaces of activated platelets", "of activated platelets catalyzes", "activated platelets catalyzes the", "platelets catalyzes the formation", "catalyzes the formation of activated", "the formation of activated factor", "formation of activated factor x", "of activated factor x with", "activated factor x with high", "factor x with high efficiency.", "x with high efficiency. a", "with high efficiency. a substitution", "high efficiency. a substitution of", "efficiency. a substitution of leucine", "a substitution of leucine for", "substitution of leucine for arginine", "of leucine for arginine at", "leucine for arginine at residue", "for arginine at residue 384", "arginine at residue 384 in", "at residue 384 in fix", "384 in fix fix", "in fix fix r384l", "fix r384l also know", "r384l also know as", "also know as fix padua", "as fix padua is", "fix padua is a", "padua is a gain", "is a gain of function", "a gain of function mutation", "gain of function mutation that", "of function mutation that resulted", "function mutation that resulted in", "mutation that resulted in elevated", "that resulted in elevated fix", "resulted in elevated fix clotting", "in elevated fix clotting activity", "elevated fix clotting activity in", "fix clotting activity in a", "clotting activity in a patient", "activity in a patient with", "in a patient with venous", "a patient with venous thrombosis", "with venous thrombosis simioni", "venous thrombosis simioni p", "thrombosis simioni p et", "simioni p et al. 2009", "p et al. 2009 ." ] }, { "record_id": "GLY_000594_1_1984", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9672387", "r hsa", "hsa 9672387", "r hsa 9672387" ] }, { "record_id": "GLY_000594_1_1984", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f8", "f8 accelerates", "accelerates dissociation", "dissociation of", "of the", "the a2", "a2 domain", "defective f8 accelerates", "f8 accelerates dissociation", "accelerates dissociation of", "dissociation of the", "of the a2", "the a2 domain", "defective f8 accelerates dissociation", "f8 accelerates dissociation of", "accelerates dissociation of the", "dissociation of the a2", "of the a2 domain", "defective f8 accelerates dissociation of", "f8 accelerates dissociation of the", "accelerates dissociation of the a2", "dissociation of the a2 domain", "retention of", "of a2", "a2 polypeptide", "polypeptide is", "is required", "required for", "for normal", "normal stability", "stability of", "of activated", "activated factor", "factor viii", "and dissociation", "a2 correlates", "correlates with", "with fviiia", "fviiia inactivation", "inactivation and", "and consequent", "consequent loss", "loss of", "of fxase", "fxase activity.", "activity. hemophilia", "hemophilia a", "associated mutations", "r717w and", "and r717l", "within the", "the predicted", "predicted a1", "a1 a2", "a2 and", "and a2", "a2 a3", "a3 interface", "interface are", "are thought", "thought to", "to disrupt", "disrupt potential", "potential intersubunit", "intersubunit hydrogen", "hydrogen bonds", "bonds and", "and have", "have the", "the molecular", "molecular phenotype", "phenotype of", "of increased", "increased rate", "rate of", "of inactivation", "inactivation of", "of fviiia", "fviiia due", "due to", "to increased", "a2 subunit", "subunit dissociation", "pipe sw", "sw et", "et al.", "al. 1999", "hakeos wh", "wh et", "al. 2002", "retention of a2", "of a2 polypeptide", "a2 polypeptide is", "polypeptide is required", "is required for", "required for normal", "for normal stability", "normal stability of", "stability of activated", "of activated factor", "activated factor viii", "viii fviiia", "fviiia and", "and dissociation of", "dissociation of a2", "of a2 correlates", "a2 correlates with", "correlates with fviiia", "with fviiia inactivation", "fviiia inactivation and", "inactivation and consequent", "and consequent loss", "consequent loss of", "loss of fxase", "of fxase activity.", "fxase activity. hemophilia", "activity. hemophilia a", "a ha", "ha associated", "mutations r550h", "r550h a303e", "a303e s308l", "s308l n713i", "n713i r717w", "r717w and r717l", "r717l within", "within the predicted", "the predicted a1", "predicted a1 a2", "a1 a2 and", "a2 and a2", "and a2 a3", "a2 a3 interface", "a3 interface are", "interface are thought", "are thought to", "thought to disrupt", "to disrupt potential", "disrupt potential intersubunit", "potential intersubunit hydrogen", "intersubunit hydrogen bonds", "hydrogen bonds and", "bonds and have", "and have the", "have the molecular", "the molecular phenotype", "molecular phenotype of", "phenotype of increased", "of increased rate", "increased rate of", "rate of inactivation", "of inactivation of", "inactivation of fviiia", "of fviiia due", "fviiia due to", "due to increased", "to increased rate", "rate of a2", "of a2 subunit", "a2 subunit dissociation", "dissociation pipe", "pipe sw et", "sw et al.", "et al. 1999", "1999 hakeos", "hakeos wh et", "wh et al.", "et al. 2002", "retention of a2 polypeptide", "of a2 polypeptide is", "a2 polypeptide is required", "polypeptide is required for", "is required for normal", "required for normal stability", "for normal stability of", "normal stability of activated", "stability of activated factor", "of activated factor viii", "factor viii fviiia", "fviiia and dissociation", "and dissociation of a2", "dissociation of a2 correlates", "of a2 correlates with", "a2 correlates with fviiia", "correlates with fviiia inactivation", "with fviiia inactivation and", "fviiia inactivation and consequent", "inactivation and consequent loss", "and consequent loss of", "consequent loss of fxase", "loss of fxase activity.", "of fxase activity. hemophilia", "fxase activity. hemophilia a", "hemophilia a ha", "ha associated mutations", "associated mutations r550h", "n713i r717w and", "and r717l within", "r717l within the", "within the predicted a1", "the predicted a1 a2", "predicted a1 a2 and", "a1 a2 and a2", "a2 and a2 a3", "and a2 a3 interface", "a2 a3 interface are", "a3 interface are thought", "interface are thought to", "are thought to disrupt", "thought to disrupt potential", "to disrupt potential intersubunit", "disrupt potential intersubunit hydrogen", "potential intersubunit hydrogen bonds", "intersubunit hydrogen bonds and", "hydrogen bonds and have", "bonds and have the", "and have the molecular", "have the molecular phenotype", "the molecular phenotype of", "molecular phenotype of increased", "phenotype of increased rate", "of increased rate of", "increased rate of inactivation", "rate of inactivation of", "of inactivation of fviiia", "inactivation of fviiia due", "of fviiia due to", "fviiia due to increased", "due to increased rate", "to increased rate of", "increased rate of a2", "rate of a2 subunit", "of a2 subunit dissociation", "subunit dissociation pipe", "dissociation pipe sw", "pipe sw et al.", "sw et al. 1999", "al. 1999 hakeos", "1999 hakeos wh", "hakeos wh et al.", "wh et al. 2002", "retention of a2 polypeptide is", "of a2 polypeptide is required", "a2 polypeptide is required for", "polypeptide is required for normal", "is required for normal stability", "required for normal stability of", "for normal stability of activated", "normal stability of activated factor", "stability of activated factor viii", "activated factor viii fviiia", "viii fviiia and", "fviiia and dissociation of", "and dissociation of a2 correlates", "dissociation of a2 correlates with", "of a2 correlates with fviiia", "a2 correlates with fviiia inactivation", "correlates with fviiia inactivation and", "with fviiia inactivation and consequent", "fviiia inactivation and consequent loss", "inactivation and consequent loss of", "and consequent loss of fxase", "consequent loss of fxase activity.", "loss of fxase activity. hemophilia", "of fxase activity. hemophilia a", "activity. hemophilia a ha", "a ha associated", "mutations r550h a303e", "r550h a303e s308l", "a303e s308l n713i", "s308l n713i r717w", "n713i r717w and r717l", "r717w and r717l within", "and r717l within the", "r717l within the predicted", "within the predicted a1 a2", "the predicted a1 a2 and", "predicted a1 a2 and a2", "a1 a2 and a2 a3", "a2 and a2 a3 interface", "and a2 a3 interface are", "a2 a3 interface are thought", "a3 interface are thought to", "interface are thought to disrupt", "are thought to disrupt potential", "thought to disrupt potential intersubunit", "to disrupt potential intersubunit hydrogen", "disrupt potential intersubunit hydrogen bonds", "potential intersubunit hydrogen bonds and", "intersubunit hydrogen bonds and have", "hydrogen bonds and have the", "bonds and have the molecular", "and have the molecular phenotype", "have the molecular phenotype of", "the molecular phenotype of increased", "molecular phenotype of increased rate", "phenotype of increased rate of", "of increased rate of inactivation", "increased rate of inactivation of", "rate of inactivation of fviiia", "of inactivation of fviiia due", "inactivation of fviiia due to", "of fviiia due to increased", "fviiia due to increased rate", "due to increased rate of", "to increased rate of a2", "increased rate of a2 subunit", "rate of a2 subunit dissociation", "a2 subunit dissociation pipe", "subunit dissociation pipe sw", "dissociation pipe sw et", "pipe sw et al. 1999", "et al. 1999 hakeos", "al. 1999 hakeos wh", "1999 hakeos wh et", "hakeos wh et al. 2002" ] }, { "record_id": "GLY_000594_1_1985", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9672391", "r hsa", "hsa 9672391", "r hsa 9672391" ] }, { "record_id": "GLY_000594_1_1985", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f8", "f8 cleavage", "cleavage by", "by thrombin", "defective f8 cleavage", "f8 cleavage by", "cleavage by thrombin", "defective f8 cleavage by", "f8 cleavage by thrombin", "defective f8 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missense mutations within the", "missense mutations within the s577", "mutations within the s577 q584", "within the s577 q584 region", "the s577 q584 region of", "s577 q584 region of fviii", "q584 region of fviii have", "region of fviii have been", "of fviii have been associated", "fviii have been associated with", "have been associated with mild/moderate", "been associated with mild/moderate hemophilia", "associated with mild/moderate hemophilia a", "mild/moderate hemophilia a ha", "ha amano k", "amano k et al. 1998", "et al. 1998 celie", "al. 1998 celie ph", "1998 celie ph et", "celie ph et al. 1999", "et al. 1999 jenkins", "al. 1999 jenkins pv", "1999 jenkins pv et", "jenkins pv et al. 2002", "pv et al. 2002 .", "et al. 2002 . a", "al. 2002 . a functional", "2002 . a functional assay", ". a functional assay demonstrated", "a functional assay demonstrated that", "functional assay demonstrated that the", "assay demonstrated that the mutations", "demonstrated that the mutations s577f", "the mutations s577f v578a", "s577f v578a d579a", "v578a d579a and", "d579a and q584r interfere", "and q584r interfere with fviiia:fixa", "q584r interfere with fviiia:fixa mediated", "interfere with fviiia:fixa mediated stimulation", "with fviiia:fixa mediated stimulation of", "fviiia:fixa mediated stimulation of fx", "mediated stimulation of fx activation", "stimulation of fx activation thus", "of fx activation thus the", "fx activation thus the effect", "activation thus the effect of", "thus the effect of the", "the effect of the mutations", "effect of the mutations is", "of the mutations is to", "the mutations is to reduce", "mutations is to reduce the", "is to reduce the cofactor", "to reduce the cofactor potential", "reduce the cofactor potential of", "the cofactor potential of fviii", "cofactor potential of fviii in", "potential of fviii in fxa", "of fviii in fxa generation.", "fviii in fxa generation. the", "in fxa generation. the reactome", "fxa generation. the reactome event", "generation. the reactome event describes", "the reactome event describes failed", "reactome event describes failed generation", "event describes failed generation of", "describes failed generation of fxa", "failed generation of fxa as", "generation of fxa as the", "of fxa as the functional", "fxa as the functional consequence", "as the functional consequence of", "the functional consequence of the", "functional consequence of the fixa", "consequence of the fixa interaction", "of the fixa interaction with", "the fixa interaction with ha", "fixa interaction with ha associated", "interaction with ha associated fviiia", "with ha associated fviiia variants", "ha associated fviiia variants due", "associated fviiia variants due to", "fviiia variants due to reduced", "variants due to reduced ability", "due to reduced ability of", "to reduced ability of defective", "reduced ability of defective fviii", "ability of defective fviii to", "of defective fviii to act", "defective fviii to act as", "fviii to act as a", "to act as a cofactor", "act as a cofactor for", "as a cofactor for fixa", "a cofactor for fixa within", "cofactor for fixa within the", "for fixa within the intrinsic", "fixa within the intrinsic tenase", "within the intrinsic tenase complex." ] }, { "record_id": "GLY_000594_1_1989", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9672397", "r hsa", "hsa 9672397", "r hsa 9672397" ] }, { "record_id": "GLY_000594_1_1989", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f8", "f8 secretion", "defective f8 secretion", "hemophilia a", "is a", "a bleeding", "bleeding disorder", "disorder caused", "caused by", "by lack", "lack of", "of or", "or a", "a defective", "defective factor", "factor viii", "protein and", "and results", "results from", "from defects", "defects in", "in the", "the f8", "f8 gene", "peyvandi f", "f et", "et al.", "al. 2016", "2016 .

              in", ".

              in healthy", "healthy individuals", "fviii is", "is synthesized", "synthesized as", "as a", "a large", "large glycoprotein", "glycoprotein of", "of 2351", "2351 amino", "amino acids", "acids with", "with a", "a discrete", "discrete domain", "domain structure:", "structure: a1", "a1 a2", "a2 b", "b a3", "a3 c1", "c1 c2", "wood wi", "wi et", "al. 1984", "vehar ga", "ga et", "toole jj", "jj et", "1984 .", ". upon", "upon synthesis", "is translocated", "translocated into", "into the", "the lumen", "lumen of", "of the", "the endoplasmic", "endoplasmic reticulum", "where it", "it undergoes", "undergoes extensive", "extensive processing", "processing including", "including cleavage", "cleavage of", "of a", "a signal", "signal peptide", "peptide and", "and n", "n linked", "linked glycosylation", "glycosylation at", "at asparagine", "asparagine residues", "kaufman rj", "rj et", "al. 1988", "rj 1998", "1998 .", ". in", "the er", "er lumen", "of mammalian", "mammalian cells", "cells fviii", "fviii interacts", "interacts with", "with the", "the protein", "protein chaperones", "chaperones calnexin", "and immunoglobulin", "immunoglobulin binding", "binding protein", "bip or", "or grp78", "that facilitate", "facilitate proper", "proper folding", "folding of", "of proteins", "proteins prior", "prior to", "to trafficking", "trafficking to", "to the", "the golgi", "golgi compartment", "marquette ka", "ka et", "al. 1995", "swaroop m", "m et", "al. 1997", "pipe sw", "sw et", "al. 1998", ". trafficking", "trafficking from", "from the", "er to", "compartment is", "is facilitated", "facilitated by", "by lman1", "lman1 and", "and multiple", "multiple combined", "combined factor", "factor deficiency", "deficiency 2", "cargo receptor", "receptor complex", "zhang b", "b et", "al. 2005", "c et", "al. 2010", "2013 .", ". within", "within the", "golgi apparatus", "is subject", "subject to", "to further", "further processing", "including modification", "modification of", "the n", "linked oligosaccharides", "oligosaccharides to", "to complex", "complex type", "type structures", "o linked", "and sulfation", "sulfation of", "of specific", "specific tyr", "tyr residues", "upon secretion", "secretion from", "the cell", "is cleaved", "cleaved at", "at two", "two sites", "sites in", "the b", "b domain", "domain to", "to form", "form a", "a heterodimer", "heterodimer consisting", "consisting of", "the heavy", "heavy chain", "chain containing", "containing the", "the a1", "b domains", "domains in", "in a", "a metal", "metal ion", "ion dependent", "dependent complex", "complex with", "the light", "light chain", "chain consisting", "the a3", "c2 domains", "1998 .

              the", ".

              the reactome", "reactome event", "event describes", "describes defects", "defects within", "the secretory", "secretory pathway", "pathway due", "due to", "to mutations", "mutations in", "gene that", "that can", "can impair", "impair fviii", "fviii synthesis", "intracellular processing", "processing and", "and transport", "transport which", "which result", "result in", "a lack", "lack or", "or reduced", "reduced levels", "levels of", "the plasma", "plasma fviii", "fviii protein.", "protein. the", "the module", "module includes", "includes also", "also an", "an event", "event of", "of defective", "defective post", "post translational", "translational tyrosine", "tyrosine sulfonation", "sulfonation of", "of fviii", "fviii in", "apparatus that", "that is", "is required", "required for", "for the", "the optimal", "optimal interaction", "interaction between", "between the", "the secreted", "secreted fviii", "fviii and", "and the", "the von", "von willebrand", "willebrand factor", "vwf .", "a ha", "ha is", "is a bleeding", "a bleeding disorder", "bleeding disorder caused", "disorder caused by", "caused by lack", "by lack of", "lack of or", "of or a", "or a defective", "a defective factor", "defective factor viii", "viii fviii", "fviii protein", "protein and results", "and results from", "results from defects", "from defects in", "defects in the", "in the f8", "the f8 gene", "gene peyvandi", "peyvandi f et", "f et al.", "et al. 2016", "al. 2016 .

              in", "2016 .

              in healthy", ".

              in healthy individuals", "individuals fviii", "fviii is synthesized", "is synthesized as", "synthesized as a", "as a large", "a large glycoprotein", "large glycoprotein of", "glycoprotein of 2351", "of 2351 amino", "2351 amino acids", "amino acids with", "acids with a", "with a discrete", "a discrete domain", "discrete domain structure:", "domain structure: a1", "structure: a1 a2", "a1 a2 b", "a2 b a3", "b a3 c1", "a3 c1 c2", "c2 wood", "wood wi et", "wi et al.", "et al. 1984", "1984 vehar", "vehar ga et", "ga et al.", "1984 toole", "toole jj et", "jj et al.", "al. 1984 .", "1984 . upon", ". upon synthesis", "synthesis fviii", "fviii is translocated", "is translocated into", "translocated into the", "into the lumen", "the lumen of", "lumen of the", "of the endoplasmic", "the endoplasmic reticulum", "reticulum er", "where it undergoes", "it undergoes extensive", "undergoes extensive processing", "extensive processing including", "processing including cleavage", "including cleavage of", "cleavage of a", "of a signal", "a signal peptide", "signal peptide and", "peptide and n", "and n linked", "n linked glycosylation", "linked glycosylation at", "glycosylation at asparagine", "at asparagine residues", "residues kaufman", "kaufman rj et", "rj et al.", "et al. 1988", "1988 1997", "1997 kaufman", "kaufman rj 1998", "rj 1998 .", "1998 . in", ". in the", "in the er", "the er lumen", "er lumen of", "lumen of mammalian", "of mammalian cells", "mammalian cells fviii", "cells fviii interacts", "fviii interacts with", "interacts with the", "with the protein", "the protein chaperones", "protein chaperones calnexin", "calnexin cnx", "calreticulin crt", "and immunoglobulin binding", "immunoglobulin binding protein", "protein bip", "bip or grp78", "grp78 that", "that facilitate proper", "facilitate proper folding", "proper folding of", "folding of proteins", "of proteins prior", "proteins prior to", "prior to trafficking", "to trafficking to", "trafficking to the", "to the golgi", "the golgi compartment", "compartment marquette", "marquette ka et", "ka et al.", "et al. 1995", "1995 swaroop", "swaroop m et", "m et al.", "et al. 1997", "1997 pipe", "pipe sw et", "sw et al.", "et al. 1998", "1998 kaufman", "1998 . trafficking", ". trafficking from", "trafficking from the", "from the er", "the er to", "er to the", "golgi compartment is", "compartment is facilitated", "is facilitated by", "facilitated by lman1", "by lman1 and", "lman1 and multiple", "and multiple combined", "multiple combined factor", "combined factor deficiency", "factor deficiency 2", "2 mcfd2", "mcfd2 cargo", "cargo receptor complex", "complex zhang", "zhang b et", "b et al.", "et al. 2005", "2005 zheng", "zheng c", "c et al.", "et al. 2010", "2010 2013", "2013 . within", ". within the", "within the golgi", "the golgi apparatus", "apparatus fviii", "fviii is subject", "is subject to", "subject to further", "to further processing", "including modification of", "modification of the", "of the n", "the n linked", "n linked oligosaccharides", "linked oligosaccharides to", "oligosaccharides to complex", "to complex type", "complex type structures", "structures o", "o linked glycosylation", "glycosylation and", "and sulfation of", "sulfation of specific", "of specific tyr", "specific tyr residues", "1998 . upon", ". upon secretion", "upon secretion from", "secretion from the", "from the cell", "cell fviii", "fviii is cleaved", "is cleaved at", "cleaved at two", "at two sites", "two sites in", "sites in the", "in the b", "the b domain", "b domain to", "domain to form", "to form a", "form a heterodimer", "a heterodimer consisting", "heterodimer consisting of", "consisting of the", "of the heavy", "the heavy chain", "heavy chain containing", "chain containing the", "containing the a1", "the a1 a2", "a2 b domains", "b domains in", "domains in a", "in a metal", "a metal ion", "metal ion dependent", "ion dependent complex", "dependent complex with", "complex with the", "with the light", "the light chain", "light chain consisting", "chain consisting of", "of the a3", "the a3 c1", "c1 c2 domains", "domains kaufman", "rj 1998 .

              the", "1998 .

              the reactome", ".

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              in", "al. 2016 .

              in healthy", "2016 .

              in healthy individuals", "healthy individuals fviii", "individuals fviii is", "fviii is synthesized as", "is synthesized as a", "synthesized as a large", "as a large glycoprotein", "a large glycoprotein of", "large glycoprotein of 2351", "glycoprotein of 2351 amino", "of 2351 amino acids", "2351 amino acids with", "amino acids with a", "acids with a discrete", "with a discrete domain", "a discrete domain structure:", "discrete domain structure: a1", "domain structure: a1 a2", "structure: a1 a2 b", "a1 a2 b a3", "a2 b a3 c1", "b a3 c1 c2", "c1 c2 wood", "c2 wood wi", "wood wi et al.", "wi et al. 1984", "al. 1984 vehar", "1984 vehar ga", "vehar ga et al.", "ga et al. 1984", "al. 1984 toole", "1984 toole jj", "toole jj et al.", "jj et al. 1984", "et al. 1984 .", "al. 1984 . upon", "1984 . upon synthesis", "upon synthesis fviii", "synthesis fviii is", "fviii is translocated into", "is translocated into the", "translocated into the lumen", "into the lumen of", "the lumen of the", "lumen of the endoplasmic", "of the endoplasmic reticulum", "endoplasmic reticulum er", "er where", "where it undergoes extensive", "it undergoes extensive processing", "undergoes extensive processing including", "extensive processing including cleavage", "processing including cleavage of", "including cleavage of a", "cleavage of a signal", "of a signal peptide", "a signal peptide and", "signal peptide and n", "peptide and n linked", "and n linked glycosylation", "n linked glycosylation at", "linked glycosylation at asparagine", "glycosylation at asparagine residues", "asparagine residues kaufman", "residues kaufman rj", "kaufman rj et al.", "rj et al. 1988", "al. 1988 1997", "1997 kaufman rj", "kaufman rj 1998 .", "rj 1998 . in", "1998 . in the", ". in the er", "in the er lumen", "the er lumen of", "er lumen of mammalian", "lumen of mammalian cells", "of mammalian cells fviii", "mammalian cells fviii interacts", "cells fviii interacts with", "fviii interacts with the", "interacts with the protein", "with the protein chaperones", "the protein chaperones calnexin", "chaperones calnexin cnx", "cnx calreticulin", "crt and", "and immunoglobulin binding protein", "binding protein bip", "protein bip or", "or grp78 that", "grp78 that facilitate", "that facilitate proper folding", "facilitate proper folding of", "proper folding of proteins", "folding of proteins prior", "of proteins prior to", "proteins prior to trafficking", "prior to trafficking to", "to trafficking to the", "trafficking to the golgi", "to the golgi compartment", "golgi compartment marquette", "compartment marquette ka", "marquette ka et al.", "ka et al. 1995", "al. 1995 swaroop", "1995 swaroop m", "swaroop m et al.", "m et al. 1997", "al. 1997 pipe", "1997 pipe sw", "pipe sw et al.", "sw et al. 1998", "al. 1998 kaufman", "1998 kaufman rj", "rj et al. 1997", "al. 1997 kaufman", "rj 1998 . trafficking", "1998 . trafficking from", ". trafficking from the", "trafficking from the er", "from the er to", "the er to the", "er to the golgi", "the golgi compartment is", "golgi compartment is facilitated", "compartment is facilitated by", "is facilitated by lman1", "facilitated by lman1 and", "by lman1 and multiple", "lman1 and multiple combined", "and multiple combined factor", "multiple combined factor deficiency", "combined factor deficiency 2", "deficiency 2 mcfd2", "mcfd2 cargo receptor", "receptor complex zhang", "complex zhang b", "zhang b et al.", "b et al. 2005", "al. 2005 zheng", "zheng c et", "c et al. 2010", "al. 2010 2013", "2010 2013 .", "2013 . within the", ". within the golgi", "within the golgi apparatus", "golgi apparatus fviii", "apparatus fviii is", "fviii is subject to", "is subject to further", "subject to further processing", "further processing including", "processing including modification", "including modification of the", "modification of the n", "of the n linked", "the n linked oligosaccharides", "n linked oligosaccharides to", "linked oligosaccharides to complex", "oligosaccharides to complex type", "to complex type structures", "type structures o", "structures o linked", "linked glycosylation and", "glycosylation and sulfation", "and sulfation of specific", "sulfation of specific tyr", "of specific tyr residues", "tyr residues kaufman", "rj 1998 . upon", "1998 . upon secretion", ". upon secretion from", "upon secretion from the", "secretion from the cell", "the cell fviii", "cell fviii is", "fviii is cleaved at", "is cleaved at two", "cleaved at two sites", "at two sites in", "two sites in the", "sites in the b", "in the b domain", "the b domain to", "b domain to form", "domain to form a", "to form a heterodimer", "form a heterodimer consisting", "a heterodimer consisting of", "heterodimer consisting of the", "consisting of the heavy", "of the heavy chain", "the heavy chain containing", "heavy chain containing the", "chain containing the a1", "containing the a1 a2", "the a1 a2 b", "a1 a2 b domains", "a2 b domains in", "b domains in a", "domains in a metal", "in a metal ion", "a metal ion dependent", "metal ion dependent complex", "ion dependent complex with", "dependent complex with the", "complex with the light", "with the light chain", "the light chain consisting", "light chain consisting of", "chain consisting of the", "consisting of the a3", "of the a3 c1", "the a3 c1 c2", "a3 c1 c2 domains", "c2 domains kaufman", "domains kaufman rj", "kaufman rj 1998 .

              the", "rj 1998 .

              the reactome", "1998 .

              the reactome event", ".

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              in", "et al. 2016 .

              in healthy", "al. 2016 .

              in healthy individuals", ".

              in healthy individuals fviii", "healthy individuals fviii is", "individuals fviii is synthesized", "fviii is synthesized as a", "is synthesized as a large", "synthesized as a large glycoprotein", "as a large glycoprotein of", "a large glycoprotein of 2351", "large glycoprotein of 2351 amino", "glycoprotein of 2351 amino acids", "of 2351 amino acids with", "2351 amino acids with a", "amino acids with a discrete", "acids with a discrete domain", "with a discrete domain structure:", "a discrete domain structure: a1", "discrete domain structure: a1 a2", "domain structure: a1 a2 b", "structure: a1 a2 b a3", "a1 a2 b a3 c1", "a2 b a3 c1 c2", "a3 c1 c2 wood", "c1 c2 wood wi", "c2 wood wi et", "wood wi et al. 1984", "et al. 1984 vehar", "al. 1984 vehar ga", "1984 vehar ga et", "vehar ga et al. 1984", "et al. 1984 toole", "al. 1984 toole jj", "1984 toole jj et", "toole jj et al. 1984", "jj et al. 1984 .", "et al. 1984 . upon", "al. 1984 . upon synthesis", ". upon synthesis fviii", "upon synthesis fviii is", "synthesis fviii is translocated", "fviii is translocated into the", "is translocated into the lumen", "translocated into the lumen of", "into the lumen of the", "the lumen of the endoplasmic", "lumen of the endoplasmic reticulum", "the endoplasmic reticulum er", "er where it", "where it undergoes extensive processing", "it undergoes extensive processing including", "undergoes extensive processing including cleavage", "extensive processing including cleavage of", "processing including cleavage of a", "including cleavage of a signal", "cleavage of a signal peptide", "of a signal peptide and", "a signal peptide and n", "signal peptide and n linked", "peptide and n linked glycosylation", "and n linked glycosylation at", "n linked glycosylation at asparagine", "linked glycosylation at asparagine residues", "at asparagine residues kaufman", "asparagine residues kaufman rj", "residues kaufman rj et", "kaufman rj et al. 1988", "et al. 1988 1997", "1988 1997 kaufman", "1997 kaufman rj 1998", "kaufman rj 1998 . in", "rj 1998 . in the", "1998 . in the er", ". in the er lumen", "in the er lumen of", "the er lumen of mammalian", "er lumen of mammalian cells", "lumen of mammalian cells fviii", "of mammalian cells fviii interacts", "mammalian cells fviii interacts with", "cells fviii interacts with the", "fviii interacts with the protein", "interacts with the protein chaperones", "with the protein chaperones calnexin", "protein chaperones calnexin cnx", "crt and immunoglobulin", "immunoglobulin binding protein bip", "binding protein bip or", "protein bip or grp78", "bip or grp78 that", "or grp78 that facilitate", "grp78 that facilitate proper", "that facilitate proper folding of", "facilitate proper folding of proteins", "proper folding of proteins prior", "folding of proteins prior to", "of proteins prior to trafficking", "proteins prior to trafficking to", "prior to trafficking to the", "to trafficking to the golgi", "trafficking to the golgi compartment", "the golgi compartment marquette", "golgi compartment marquette ka", "compartment marquette ka et", "marquette ka et al. 1995", "et al. 1995 swaroop", "al. 1995 swaroop m", "1995 swaroop m et", "swaroop m et al. 1997", "et al. 1997 pipe", "al. 1997 pipe sw", "1997 pipe sw et", "pipe sw et al. 1998", "et al. 1998 kaufman", "al. 1998 kaufman rj", "1998 kaufman rj et", "kaufman rj et al. 1997", "et al. 1997 kaufman", "al. 1997 kaufman rj", "kaufman rj 1998 . trafficking", "rj 1998 . trafficking from", "1998 . trafficking from the", ". trafficking from the er", "trafficking from the er to", "from the er to the", "the er to the golgi", "er to the golgi compartment", "to the golgi compartment is", "the golgi compartment is facilitated", "golgi compartment is facilitated by", "compartment is facilitated by lman1", "is facilitated by lman1 and", "facilitated by lman1 and multiple", "by lman1 and multiple combined", "lman1 and multiple combined factor", "and multiple combined factor deficiency", "multiple combined factor deficiency 2", "factor deficiency 2 mcfd2", "2 mcfd2 cargo", "mcfd2 cargo receptor complex", "cargo receptor complex zhang", "receptor complex zhang b", "complex zhang b et", "zhang b et al. 2005", "et al. 2005 zheng", "2005 zheng c", "zheng c et al.", "et al. 2010 2013", "al. 2010 2013 .", "2010 2013 . within", "2013 . within the golgi", ". within the golgi apparatus", "the golgi apparatus fviii", "golgi apparatus fviii is", "apparatus fviii is subject", "fviii is subject to further", "is subject to further processing", "to further processing including", "further processing including modification", "processing including modification of", "including modification of the n", "modification of the n linked", "of the n linked oligosaccharides", "the n linked oligosaccharides to", "n linked oligosaccharides to complex", "linked oligosaccharides to complex type", "oligosaccharides to complex type structures", "complex type structures o", "type structures o linked", "structures o linked glycosylation", "o linked glycosylation and", "linked glycosylation and sulfation", "glycosylation and sulfation of", "and sulfation of specific tyr", "sulfation of specific tyr residues", "specific tyr residues kaufman", "tyr residues kaufman rj", "residues kaufman rj 1998", "kaufman rj 1998 . upon", "rj 1998 . upon secretion", "1998 . upon secretion from", ". upon secretion from the", "upon secretion from the cell", "from the cell fviii", "the cell fviii is", "cell fviii is cleaved", "fviii is cleaved at two", "is cleaved at two sites", "cleaved at two sites in", "at two sites in the", "two sites in the b", "sites in the b domain", "in the b domain to", "the b domain to form", "b domain to form a", "domain to form a heterodimer", "to form a heterodimer consisting", "form a heterodimer consisting of", "a heterodimer consisting of the", "heterodimer consisting of the heavy", "consisting of the heavy chain", "of the heavy chain containing", 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              the reactome", "rj 1998 .

              the reactome event", "1998 .

              the reactome event describes", ".

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"reduced levels of the plasma", "levels of the plasma fviii", "of the plasma fviii protein.", "the plasma fviii protein. the", "plasma fviii protein. the module", "fviii protein. the module includes", "protein. the module includes also", "the module includes also an", "module includes also an event", "includes also an event of", "also an event of defective", "an event of defective post", "event of defective post translational", "of defective post translational tyrosine", "defective post translational tyrosine sulfonation", "post translational tyrosine sulfonation of", "translational tyrosine sulfonation of fviii", "tyrosine sulfonation of fviii in", "sulfonation of fviii in the", "of fviii in the golgi", "fviii in the golgi apparatus", "in the golgi apparatus that", "the golgi apparatus that is", "golgi apparatus that is required", "apparatus that is required for", "that is required for the", "is required for the optimal", "required for the optimal interaction", "for the optimal interaction between", "the optimal interaction between the", "optimal interaction between the secreted", "interaction between the secreted fviii", "between the secreted fviii and", "the secreted fviii and the", "secreted fviii and the von", "fviii and the von willebrand", "and the von willebrand factor", "von willebrand factor vwf", "willebrand factor vwf ." ] }, { "record_id": "GLY_000594_1_1990", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9673202", "r hsa", "hsa 9673202", "r hsa 9673202" ] }, { "record_id": "GLY_000594_1_1990", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f9", "f9 variant", "variant does", "does not", "not activate", "activate fx", "defective f9 variant", "f9 variant does", "variant does not", "does not activate", "not activate fx", "defective f9 variant does", "f9 variant does not", "variant does not activate", "does not activate fx", "defective f9 variant 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              the", "2019 .

              the reactome", ".

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              the", "al. 2019 .

              the reactome", "2019 .

              the reactome event", ".

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              the", "et al. 2019 .

              the reactome", "al. 2019 .

              the reactome event", "2019 .

              the reactome event describes", ".

              the reactome event describes intracellular", "reactome event describes intracellular accumulation", "event describes intracellular accumulation and/or", "describes intracellular accumulation and/or decreased", "intracellular accumulation and/or decreased secretion", "accumulation and/or decreased secretion of", "and/or decreased secretion of fix", "decreased secretion of fix due", "secretion of fix due to", "of fix due to different", "fix due to different hb", "due to different hb related", "to different hb related genetic", "different hb related genetic alterations", "hb related genetic alterations spread", "related genetic alterations spread throughout", "genetic alterations spread throughout the", "alterations spread throughout the f9", "spread throughout the f9 gene." ] }, { "record_id": "GLY_000594_1_1992", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9673221", "r hsa", "hsa 9673221", "r hsa 9673221" ] }, { "record_id": "GLY_000594_1_1992", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f9", "f9 activation", "defective f9 activation", "deficiency or", "or dysfunction", "dysfunction of", "of fix", "fix leads", "leads to", "to hemophilia", "hemophilia b", "an x", "x linked", "bleeding disorder.", "disorder. on", "on a", "a molecular", "molecular basis", "hb is", "is due", "due to", "to a", "a heterogeneous", "heterogeneous spectrum", "spectrum of", "of mutations", "mutations spread", "spread throughout", "throughout the", "the f9", "f9 gene", "rallapalli pm", "pm et", "et al.", "al. 2013", "2013 .

              the", ".

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              ", "deficiency or dysfunction", "or dysfunction of", "dysfunction of fix", "of fix leads", "fix leads to", "leads to hemophilia", "to hemophilia b", "b hb", "an x linked", "linked recessive", "recessive bleeding", "bleeding disorder. on", "disorder. on a", "on a molecular", "a molecular basis", "basis hb", "hb is due", "is due to", "due to a", "to a heterogeneous", "a heterogeneous spectrum", "heterogeneous spectrum of", "spectrum of mutations", "of mutations spread", "mutations spread throughout", "spread throughout the", "throughout the f9", "the f9 gene", "gene rallapalli", "rallapalli pm et", "pm et al.", "et al. 2013", "al. 2013 .

              the", "2013 .

              the reactome", ".

              the reactome event", "reactome event describes", "event describes the", "describes the defective", "the defective proteolytic", "defective proteolytic activation", "proteolytic activation of", "activation of fix", "of fix by", "fix by factor", "by factor xia", "factor xia due", "xia due to", "due to the", "to the presence", "the presence of", "presence of hb", "of hb associated", "hb associated point", "associated point mutations", "point mutations r191c", "r191c r191h", "r191h r226q", "r226q and r226w", "and r226w in", "r226w in the", "in the cleavage", "the cleavage sites", "cleavage sites of", "sites of fix", "fix liddell", "liddell mb et", "mb et al.", "et al. 1989", "1989 monroe", "monroe dm et", "dm et al.", "1989 suehiro", "suehiro k et", "k et al.", "1989 diuguid", "diuguid dl et", "dl et al.", "1989 bertina", "bertina rm et", "rm et al.1990", "et al.1990 .", "al.1990 . in", ". in addition", "addition naturally", "naturally occurring point", "occurring point mutations", "point mutations in", "mutations in the", "in the fix", "the fix propeptide", "fix propeptide sequence", "propeptide sequence such", "sequence such as", "such as n43q", "n43q n43l", "n43l or n46s", "or n46s are", "n46s are also", "are also annotated", "also annotated here.", "annotated here. these", "here. these fix", "these fix variants", "fix variants are", "variants are secreted", "are secreted into", "secreted into the", "into the circulation", "the circulation with", "circulation with a", "with a mutant", "a mutant 18", "mutant 18 amino", "18 amino acid", "amino acid propeptide", "acid propeptide still", "propeptide still attached", "attached bentley", "bentley ak et", "ak et al.", "et al. 1986", "1986 galeffi", "galeffi p &", "p & brownlee", "& brownlee gg", "brownlee gg 1987", "gg 1987 .", "1987 . the", ". the unprocessed", "the unprocessed fix", "unprocessed fix variants", "fix variants were", "variants were found", "were found to", "found to affect", "to affect the", "affect the function", "the function of", "function of the", "of the protein", "the protein by", "protein by destabilizing", "by destabilizing the", "destabilizing the calcium", "the calcium induced", "calcium induced conformation", "induced conformation of", "conformation of fix", "fix wojcik", "wojcik eg et", "eg et al.", "et al. 1997", "1997 and", "and showed delayed", "showed delayed activation", "delayed activation by", "activation by fxia", "fxia liddell", "1989 ware", "ware j et", "j et al.", "1989 de", "de la salle", "la salle c", "salle c et", "c et al.", "et al. 1993", "1993 wojcik", "1997 bristol", "bristol ja et", "ja et al.", "al. 1993 .


              ", "deficiency or dysfunction of", "or dysfunction of fix", "dysfunction of fix leads", "of fix leads to", "fix leads to hemophilia", "leads to hemophilia b", "hemophilia b hb", "hb an", "x linked recessive", "recessive bleeding disorder.", "bleeding disorder. on a", "disorder. on a molecular", "on a molecular basis", "molecular basis hb", "basis hb is", "hb is due to", "is due to a", "due to a heterogeneous", "to a heterogeneous spectrum", "a heterogeneous spectrum of", "heterogeneous spectrum of mutations", "spectrum of mutations spread", "of mutations spread throughout", "mutations spread throughout the", "spread throughout the f9", "throughout the f9 gene", "f9 gene rallapalli", "gene rallapalli pm", "rallapalli pm et al.", "pm et al. 2013", "et al. 2013 .

              the", "al. 2013 .

              the reactome", "2013 .

              the reactome event", ".

              the reactome event describes", "reactome event describes the", "event describes the defective", "describes the defective proteolytic", "the defective proteolytic activation", "defective proteolytic activation of", "proteolytic activation of fix", "activation of fix by", "of fix by factor", "fix by factor xia", "by factor xia due", "factor xia due to", "xia due to the", "due to the presence", "to the presence of", "the presence of hb", "presence of hb associated", "of hb associated point", "hb associated point mutations", "associated point mutations r191c", "mutations r191c r191h", "r191h r226q and", "r226q and r226w in", "and r226w in the", "r226w in the cleavage", "in the cleavage sites", "the cleavage sites of", "cleavage sites of fix", "of fix liddell", "fix liddell mb", "liddell mb et al.", "mb et al. 1989", "al. 1989 monroe", "1989 monroe dm", "monroe dm et al.", "dm et al. 1989", "al. 1989 suehiro", "1989 suehiro k", "suehiro k et al.", "k et al. 1989", "al. 1989 diuguid", "1989 diuguid dl", "diuguid dl et al.", "dl et al. 1989", "al. 1989 bertina", "1989 bertina rm", "bertina rm et al.1990", "rm et al.1990 .", "et al.1990 . in", "al.1990 . in addition", "in addition naturally", "addition naturally occurring", "naturally occurring point mutations", "occurring point mutations in", "point mutations in the", "mutations in the fix", "in the fix propeptide", "the fix propeptide sequence", "fix propeptide sequence such", "propeptide sequence such as", "sequence such as n43q", "as n43q n43l", "n43q n43l or", "n43l or n46s are", "or n46s are also", "n46s are also annotated", "are also annotated here.", "also annotated here. these", "annotated here. these fix", "here. these fix variants", "these fix variants are", "fix variants are secreted", "variants are secreted into", "are secreted into the", "secreted into the circulation", "into the circulation with", "the circulation with a", "circulation with a mutant", "with a mutant 18", "a mutant 18 amino", "mutant 18 amino acid", "18 amino acid propeptide", "amino acid propeptide still", "acid propeptide still attached", "still attached bentley", "attached bentley ak", "bentley ak et al.", "ak et al. 1986", "al. 1986 galeffi", "1986 galeffi p", "galeffi p & brownlee", "p & brownlee gg", "& brownlee gg 1987", "brownlee gg 1987 .", "gg 1987 . the", "1987 . the unprocessed", ". the unprocessed fix", "the unprocessed fix variants", "unprocessed fix variants were", "fix variants were found", "variants were found to", "were found to affect", "found to affect the", "to affect the function", "affect the function of", "the function of the", "function of the protein", "of the protein by", "the protein by destabilizing", "protein by destabilizing the", "by destabilizing the calcium", "destabilizing the calcium induced", "the calcium induced conformation", "calcium induced conformation of", "induced conformation of fix", "of fix wojcik", "fix wojcik eg", "wojcik eg et al.", "eg et al. 1997", "al. 1997 and", "1997 and showed", "and showed delayed activation", "showed delayed activation by", "delayed activation by fxia", "by fxia liddell", "fxia liddell mb", "al. 1989 ware", "1989 ware j", "ware j et al.", "j et al. 1989", "al. 1989 de", "1989 de la", "de la salle c", "la salle c et", "salle c et al.", "c et al. 1993", "al. 1993 wojcik", "1993 wojcik eg", "al. 1997 bristol", "1997 bristol ja", "bristol ja et al.", "ja et al. 1993", "et al. 1993 .


              ", "deficiency or dysfunction of fix", "or dysfunction of fix leads", "dysfunction of fix leads to", "of fix leads to hemophilia", "fix leads to hemophilia b", "to hemophilia b hb", "hb an x", "an x linked recessive", "linked recessive bleeding", "recessive bleeding disorder. on", "bleeding disorder. on a molecular", "disorder. on a molecular basis", "a molecular basis hb", "molecular basis hb is", "basis hb is due", "hb is due to a", "is due to a heterogeneous", "due to a heterogeneous spectrum", "to a heterogeneous spectrum of", "a heterogeneous spectrum of mutations", "heterogeneous spectrum of mutations spread", "spectrum of mutations spread throughout", "of mutations spread throughout the", "mutations spread throughout the f9", "spread throughout the f9 gene", "the f9 gene rallapalli", "f9 gene rallapalli pm", "gene rallapalli pm et", "rallapalli pm et al. 2013", "pm et al. 2013 .

              the", "et al. 2013 .

              the reactome", "al. 2013 .

              the reactome event", "2013 .

              the reactome event describes", ".

              the reactome event describes the", "reactome event describes the defective", "event describes the defective proteolytic", "describes the defective proteolytic activation", "the defective proteolytic activation of", "defective proteolytic activation of fix", "proteolytic activation of fix by", "activation of fix by factor", "of fix by factor xia", "fix by factor xia due", "by factor xia due to", "factor xia due to the", "xia due to the presence", "due to the presence of", "to the presence of hb", "the presence of hb associated", "presence of hb associated point", "of hb associated point mutations", "hb associated point mutations r191c", "point mutations r191c r191h", "r191c r191h r226q", "r191h r226q and r226w", "r226q and r226w in the", "and r226w in the cleavage", "r226w in the cleavage sites", "in the cleavage sites of", "the cleavage sites of fix", "sites of fix liddell", "of fix liddell mb", "fix liddell mb et", "liddell mb et al. 1989", "et al. 1989 monroe", "al. 1989 monroe dm", "1989 monroe dm et", "monroe dm et al. 1989", "et al. 1989 suehiro", "al. 1989 suehiro k", "1989 suehiro k et", "suehiro k et al. 1989", "et al. 1989 diuguid", "al. 1989 diuguid dl", "1989 diuguid dl et", "diuguid dl et al. 1989", "et al. 1989 bertina", "al. 1989 bertina rm", "1989 bertina rm et", "bertina rm et al.1990 .", "rm et al.1990 . in", "et al.1990 . in addition", ". in addition naturally", "in addition naturally occurring", "addition naturally occurring point", "naturally occurring point mutations in", "occurring point mutations in the", "point mutations in the fix", "mutations in the fix propeptide", "in the fix propeptide sequence", "the fix propeptide sequence such", "fix propeptide sequence such as", "propeptide sequence such as n43q", "such as n43q n43l", "as n43q n43l or", "n43q n43l or n46s", "n43l or n46s are also", "or n46s are also annotated", "n46s are also annotated here.", "are also annotated here. these", "also annotated here. these fix", "annotated here. these fix variants", "here. these fix variants are", "these fix variants are secreted", "fix variants are secreted into", "variants are secreted into the", "are secreted into the circulation", "secreted into the circulation with", "into the circulation with a", "the circulation with a mutant", "circulation with a mutant 18", "with a mutant 18 amino", "a mutant 18 amino acid", "mutant 18 amino acid propeptide", "18 amino acid propeptide still", "amino acid propeptide still attached", "propeptide still attached bentley", "still attached bentley ak", "attached bentley ak et", "bentley ak et al. 1986", "et al. 1986 galeffi", "al. 1986 galeffi p", "1986 galeffi p &", "galeffi p & brownlee gg", "p & brownlee gg 1987", "& brownlee gg 1987 .", "brownlee gg 1987 . the", "gg 1987 . the unprocessed", "1987 . the unprocessed fix", ". the unprocessed fix variants", "the unprocessed fix variants were", "unprocessed fix variants were found", "fix variants were found to", "variants were found to affect", "were found to affect the", "found to affect the function", "to affect the function of", "affect the function of the", "the function of the protein", "function of the protein by", "of the protein by destabilizing", "the protein by destabilizing the", "protein by destabilizing the calcium", "by destabilizing the calcium induced", "destabilizing the calcium induced conformation", "the calcium induced conformation of", "calcium induced conformation of fix", "conformation of fix wojcik", "of fix wojcik eg", "fix wojcik eg et", "wojcik eg et al. 1997", "et al. 1997 and", "al. 1997 and showed", "1997 and showed delayed", "and showed delayed activation by", "showed delayed activation by fxia", "activation by fxia liddell", "by fxia liddell mb", "fxia liddell mb et", "et al. 1989 ware", "al. 1989 ware j", "1989 ware j et", "ware j et al. 1989", "et al. 1989 de", "al. 1989 de la", "1989 de la salle", "de la salle c et", "la salle c et al.", "salle c et al. 1993", "et al. 1993 wojcik", "al. 1993 wojcik eg", "1993 wojcik eg et", "et al. 1997 bristol", "al. 1997 bristol ja", "1997 bristol ja et", "bristol ja et al. 1993", "ja et al. 1993 .


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intracellular protein", "intracellular protein leading", "protein leading to", "leading to ligand independent", "to ligand independent dimerization", "ligand independent dimerization and", "independent dimerization and constitutive", "dimerization and constitutive activation", "constitutive activation reviewed", "activation reviewed in", "reviewed in wang et", "in wang et al", "et al 2016", "2016 appiah kubi", "appiah kubi et al", "et al 2017", "al 2017 .", "2017 . to date", ". to date there", "to date there are", "date there are about", "there are about 35", "are about 35 identified", "about 35 identified pdgfr", "35 identified pdgfr fusion", "identified pdgfr fusion partners", "fusion partners most", "partners most of", "most of which form", "of which form fusions", "which form fusions with", "form fusions with pdgfrb", "with pdgfrb reviewed", "pdgfrb reviewed in", "reviewed in appiah kubi", "in appiah kubi et", "2017 . the most", ". the most common", "the most common cytosolic", "most common cytosolic fusion", "common cytosolic fusion partners", "cytosolic fusion partners of", "fusion partners of pdgfra", "partners of pdgfra is", "of pdgfra is fip1l1", "is fip1l1 an", "fip1l1 an rna", "an rna processing factor", "processing factor cools", "factor cools et", "et al 2003", "2003 stover et", "et al 2006", "2006 simon et", "et al 2008", "2008 andrae et", "2008 ozawa et", "et al 2010", "2010 appiah kubi", "2017 . fusion partners", ". fusion partners with", "fusion partners with pdgfrb", "partners with pdgfrb are", "with pdgfrb are numerous", "pdgfrb are numerous but", "are numerous but occurrence", "numerous but occurrence of", "but occurrence of these", "occurrence of these proteins", "of these proteins is", "these proteins is rare", "is rare hidalgo", "rare hidalgo curtis", "hidalgo curtis et al", "2010 reviewed in", "in addition to activating missense", "addition to activating missense mutations", "to activating missense mutations and", "activating missense mutations and in", "missense mutations and in frame", "mutations and in frame deletions", "in frame deletions pdgfra", "frame deletions pdgfra and", "deletions pdgfra and pdgfrb", "pdgfra and pdgfrb are also", "and pdgfrb are also subject", "pdgfrb are also subject to", "are also subject to gene", "also subject to gene fusion", "subject to gene fusion events", "to gene fusion events arising", "gene fusion events arising from", "fusion events arising from chromosomal", "events arising from chromosomal rearrangements.", "arising from chromosomal rearrangements. pdgfr", "from chromosomal rearrangements. pdgfr fusions", "chromosomal rearrangements. pdgfr fusions often", "rearrangements. pdgfr fusions often consist", "pdgfr fusions often consist of", "fusions often consist of the", "often consist of the cytosolic", "consist of the cytosolic domain", "of the cytosolic domain of", "the cytosolic domain of the", "cytosolic domain of the receptor", "domain of the receptor tyrosine", "of the receptor tyrosine kinase", "the receptor tyrosine kinase fused", "receptor tyrosine kinase fused to", "tyrosine kinase fused to the", "kinase fused to the n", "fused to the n terminal", "to the n terminal oligomerization", "the n terminal oligomerization domain", "n terminal oligomerization domain of", "terminal oligomerization domain of an", "oligomerization domain of an intracellular", "domain of an intracellular protein", "an intracellular protein leading", "intracellular protein leading to", "protein leading to ligand", "leading to ligand independent dimerization", "to ligand independent dimerization and", "ligand independent dimerization and constitutive", "independent dimerization and constitutive activation", "and constitutive activation reviewed", "constitutive activation reviewed in", "activation reviewed in wang", "reviewed in wang et al", "wang et al 2016", "al 2016 appiah", "2016 appiah kubi et", "kubi et al 2017", "et al 2017 .", "al 2017 . to", "2017 . to date there", ". to date there are", "to date there are about", "date there are about 35", "there are about 35 identified", "are about 35 identified pdgfr", "about 35 identified pdgfr fusion", "35 identified pdgfr fusion partners", "pdgfr fusion partners most", "fusion partners most of", "partners most of which", "most of which form fusions", "of which form fusions with", "which form fusions with pdgfrb", "fusions with pdgfrb reviewed", "with pdgfrb reviewed in", "pdgfrb reviewed in appiah", "reviewed in appiah kubi et", "in appiah kubi et al", "al 2017 . the", "2017 . the most common", ". the most common cytosolic", "the most common cytosolic fusion", "most common cytosolic fusion partners", "common cytosolic fusion partners of", "cytosolic fusion partners of pdgfra", "fusion partners of pdgfra is", "partners of pdgfra is fip1l1", "pdgfra is fip1l1 an", "is fip1l1 an rna", "fip1l1 an rna processing", "rna processing factor cools", "processing factor cools et", "factor cools et al", "cools et al 2003", "al 2003 stover", "2003 stover et al", "stover et al 2006", "al 2006 simon", "2006 simon et al", "simon et al 2008", "al 2008 andrae", "2008 andrae et al", "andrae et al 2008", "al 2008 ozawa", "2008 ozawa et al", "ozawa et al 2010", "al 2010 appiah", "2010 appiah kubi et", "al 2017 . fusion", "2017 . fusion partners with", ". fusion partners with pdgfrb", "fusion partners with pdgfrb are", "partners with pdgfrb are numerous", "with pdgfrb are numerous but", "pdgfrb are numerous but occurrence", "are numerous but occurrence of", "numerous but occurrence of these", "but occurrence of these proteins", "occurrence of these proteins is", "of these proteins is rare", "proteins is rare hidalgo", "is rare hidalgo curtis", "rare hidalgo curtis et", "curtis et al 2010", "al 2010 reviewed", "2010 reviewed in wang" ] }, { "record_id": "GLY_000594_1_1995", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9674519", "r hsa", "hsa 9674519", "r hsa 9674519" ] }, { "record_id": "GLY_000594_1_1995", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective f8", "f8 sulfation", "sulfation at", "at y1699", "defective f8 sulfation", "f8 sulfation at", "sulfation at y1699", "defective f8 sulfation at", "f8 sulfation at y1699", "defective f8 sulfation at y1699", "hemophilia a", "is a", "a bleeding", "bleeding disorder", "disorder caused", "caused by", "by lack", "lack of", "of or", "or a", "a defective", "defective factor", "factor viii", "protein and", "and results", "results from", "from defects", "defects in", "in the", "the f8", "f8 gene", "peyvandi f", "f et", "et al.", "al. 2016", "2016 .

              in", ".

              in healthy", "healthy individuals", "fviii is", "is synthesized", "synthesized as", "as a", "a large", "large glycoprotein", "glycoprotein of", "of 2351", "2351 amino", "amino acids", "acids with", "with a", "a discrete", "discrete domain", "domain structure:", "structure: a1", "a1 a2", "a2 b", "b a3", "a3 c1", "c1 c2", "wood wi", "wi et", "al. 1984", "vehar ga", "ga et", "toole jj", "jj et", "1984 .", ". upon", "upon synthesis", "is translocated", "translocated into", "into the", "the lumen", "lumen of", "of the", "the endoplasmic", "endoplasmic reticulum", "where it", "it undergoes", "undergoes extensive", "extensive processing", "processing including", "including cleavage", "cleavage of", "of a", "a signal", "signal peptide", "peptide and", "and n", "n linked", "linked glycosylation", "glycosylation at", "at asparagine", "asparagine residues", "kaufman rj", "rj et", "al. 1988", "rj 1998", "1998 .", ". in", "the er", "er lumen", "of mammalian", "mammalian cells", "cells fviii", "fviii interacts", "interacts with", "with the", "the protein", "protein chaperones", "chaperones calnexin", "and immunoglobulin", "immunoglobulin binding", "binding protein", "bip or", "or grp78", "that facilitate", "facilitate proper", "proper folding", "folding of", "of proteins", "proteins prior", "prior to", "to trafficking", "trafficking to", "to the", "the golgi", "golgi compartment", "marquette ka", "ka et", "al. 1995", "swaroop m", "m et", "al. 1997", "pipe sw", "sw et", "al. 1998", ". trafficking", "trafficking from", "from the", "er to", "compartment is", "is facilitated", "facilitated by", "by lman1", "lman1 and", "and multiple", "multiple combined", "combined factor", "factor deficiency", "deficiency 2", "cargo receptor", "receptor complex", "zhang b", "b et", "al. 2005", "c et", "al. 2010", "2013 .", ". within", "within the", "golgi apparatus", "is subject", "subject to", "to further", "further processing", "including modification", "modification of", "the n", "linked oligosaccharides", "oligosaccharides to", "to complex", "complex type", "type structures", "o linked", "and sulfation", "sulfation of", "of specific", "specific tyr", "tyr residues", "upon secretion", "secretion from", "the cell", "is cleaved", "cleaved at", "at two", "two sites", "sites in", "the b", "b domain", "domain to", "to form", "form a", "a heterodimer", "heterodimer consisting", "consisting of", "the heavy", "heavy chain", "chain containing", "containing the", "the a1", "b domains", "domains in", "in a", "a metal", "metal ion", "ion dependent", "dependent complex", "complex with", "the light", "light chain", "chain consisting", "the a3", "c2 domains", "1998 .

              the", ".

              the reactome", "reactome event", "event describes", "describes defects", "defects within", "the secretory", "secretory pathway", "pathway due", "due to", "to mutations", "mutations in", "gene that", "that can", "can impair", "impair fviii", "fviii synthesis", "intracellular processing", "processing and", "and transport", "transport which", "which result", "result in", "a lack", "lack or", "or reduced", "reduced levels", "levels of", "the plasma", "plasma fviii", "fviii protein.", "protein. the", "the module", "module includes", "includes also", "also an", "an event", "event of", "of defective", "defective post", "post translational", "translational tyrosine", "tyrosine sulfonation", "sulfonation of", "of fviii", "fviii in", "apparatus that", "that is", "is required", "required for", "for the", "the optimal", "optimal interaction", "interaction between", "between the", "the secreted", "secreted fviii", "fviii and", "and the", "the von", "von willebrand", "willebrand factor", "vwf .", "a ha", "ha is", "is a bleeding", "a bleeding disorder", "bleeding disorder caused", "disorder caused by", "caused by lack", "by lack of", "lack of or", "of or a", "or a defective", "a defective factor", "defective factor viii", "viii fviii", "fviii protein", "protein and results", "and results from", "results from defects", "from defects in", "defects in the", "in the f8", "the f8 gene", "gene peyvandi", "peyvandi f et", "f et al.", "et al. 2016", "al. 2016 .

              in", "2016 .

              in healthy", ".

              in healthy individuals", "individuals fviii", "fviii is synthesized", "is synthesized as", "synthesized as a", "as a large", "a large glycoprotein", "large glycoprotein of", "glycoprotein of 2351", "of 2351 amino", "2351 amino acids", "amino acids with", "acids with a", "with a discrete", "a discrete domain", "discrete domain structure:", "domain structure: a1", "structure: a1 a2", "a1 a2 b", "a2 b a3", "b a3 c1", "a3 c1 c2", "c2 wood", "wood wi et", "wi et al.", "et al. 1984", "1984 vehar", "vehar ga et", "ga et al.", "1984 toole", "toole jj et", "jj et al.", "al. 1984 .", "1984 . upon", ". upon synthesis", "synthesis fviii", "fviii is translocated", "is translocated into", "translocated into the", "into the lumen", "the lumen of", "lumen of the", "of the endoplasmic", "the endoplasmic reticulum", "reticulum er", "where it undergoes", "it undergoes extensive", "undergoes extensive processing", "extensive processing including", "processing including cleavage", "including cleavage of", "cleavage of a", "of a signal", "a signal peptide", "signal peptide and", "peptide and n", "and n linked", "n linked glycosylation", "linked glycosylation at", "glycosylation at asparagine", "at asparagine residues", "residues kaufman", "kaufman rj et", "rj et al.", "et al. 1988", "1988 1997", "1997 kaufman", "kaufman rj 1998", "rj 1998 .", "1998 . in", ". in the", "in the er", "the er lumen", "er lumen of", "lumen of mammalian", "of mammalian cells", "mammalian cells fviii", "cells fviii interacts", "fviii interacts with", "interacts with the", "with the protein", "the protein chaperones", "protein chaperones calnexin", "calnexin cnx", "calreticulin crt", "and immunoglobulin binding", "immunoglobulin binding protein", "protein bip", "bip or grp78", "grp78 that", "that facilitate proper", "facilitate proper folding", "proper folding of", "folding of proteins", "of proteins prior", "proteins prior to", "prior to trafficking", "to trafficking to", "trafficking to the", "to the golgi", "the golgi compartment", "compartment marquette", "marquette ka et", "ka et al.", "et al. 1995", "1995 swaroop", "swaroop m et", "m et al.", "et al. 1997", "1997 pipe", "pipe sw et", "sw et al.", "et al. 1998", "1998 kaufman", "1998 . trafficking", ". trafficking from", "trafficking from the", "from the er", "the er to", "er to the", "golgi compartment is", "compartment is facilitated", "is facilitated by", "facilitated by lman1", "by lman1 and", "lman1 and multiple", "and multiple combined", "multiple combined factor", "combined factor deficiency", "factor deficiency 2", "2 mcfd2", "mcfd2 cargo", "cargo receptor complex", "complex zhang", "zhang b et", "b et al.", "et al. 2005", "2005 zheng", "zheng c", "c et al.", "et al. 2010", "2010 2013", "2013 . within", ". within the", "within the golgi", "the golgi apparatus", "apparatus fviii", "fviii is subject", "is subject to", "subject to further", "to further processing", "including modification of", "modification of the", "of the n", "the n linked", "n linked oligosaccharides", "linked oligosaccharides to", "oligosaccharides to complex", "to complex type", "complex type structures", "structures o", "o linked glycosylation", "glycosylation and", "and sulfation of", "sulfation of specific", "of specific tyr", "specific tyr residues", "1998 . upon", ". upon secretion", "upon secretion from", "secretion from the", "from the cell", "cell fviii", "fviii is cleaved", "is cleaved at", "cleaved at two", "at two sites", "two sites in", "sites in the", "in the b", "the b domain", "b domain to", "domain to form", "to form a", "form a heterodimer", "a heterodimer consisting", "heterodimer consisting of", "consisting of the", "of the heavy", "the heavy chain", "heavy chain containing", "chain containing the", "containing the a1", "the a1 a2", "a2 b domains", "b domains in", "domains in a", "in a metal", "a metal ion", "metal ion dependent", "ion dependent complex", "dependent complex with", "complex with the", "with the light", "the light chain", "light chain consisting", "chain consisting of", "of the a3", "the a3 c1", "c1 c2 domains", "domains kaufman", "rj 1998 .

              the", "1998 .

              the reactome", ".

              the reactome event", "reactome event describes", "event describes defects", "describes defects within", "defects within the", "within the secretory", "the secretory pathway", "secretory pathway due", "pathway due to", "due to mutations", "to mutations in", "mutations in the", "f8 gene that", "gene that can", "that can impair", "can impair fviii", "impair fviii synthesis", "synthesis folding", "folding intracellular", "intracellular processing and", "processing and transport", "and transport which", "transport which result", "which result in", "result in a", "in a lack", "a lack or", "lack or reduced", "or reduced levels", "reduced levels of", "levels of the", "of the plasma", "the plasma fviii", "plasma fviii protein.", "fviii protein. the", "protein. the module", "the module includes", "module includes also", "includes also an", "also an event", "an event of", "event of defective", "of defective post", "defective post translational", "post translational tyrosine", "translational tyrosine sulfonation", "tyrosine sulfonation of", "sulfonation of fviii", "of fviii in", "fviii in the", "in the golgi", "golgi apparatus that", "apparatus that is", "that is required", "is required for", "required for the", "for the optimal", "the optimal interaction", "optimal interaction between", "interaction between the", "between the secreted", "the secreted fviii", "secreted fviii and", "fviii and the", "and the von", "the von willebrand", "von willebrand factor", "factor vwf", "hemophilia a ha", "ha is a", "is a bleeding disorder", "a bleeding disorder caused", "bleeding disorder caused by", "disorder caused by lack", "caused by lack of", "by lack of or", "lack of or a", "of or a defective", "or a defective factor", "a defective factor viii", "factor viii fviii", "fviii protein and", "protein and results from", "and results from defects", "results from defects in", "from defects in the", "defects in the f8", "in the f8 gene", "f8 gene peyvandi", "gene peyvandi f", "peyvandi f et al.", "f et al. 2016", "et al. 2016 .

              in", "al. 2016 .

              in healthy", "2016 .

              in healthy individuals", "healthy individuals fviii", "individuals fviii is", "fviii is synthesized as", "is synthesized as a", "synthesized as a large", "as a large glycoprotein", "a large glycoprotein of", "large glycoprotein of 2351", "glycoprotein of 2351 amino", "of 2351 amino acids", "2351 amino acids with", "amino acids with a", "acids with a discrete", "with a discrete domain", "a discrete domain structure:", "discrete domain structure: a1", "domain structure: a1 a2", "structure: a1 a2 b", "a1 a2 b a3", "a2 b a3 c1", "b a3 c1 c2", "c1 c2 wood", "c2 wood wi", "wood wi et al.", "wi et al. 1984", "al. 1984 vehar", "1984 vehar ga", "vehar ga et al.", "ga et al. 1984", "al. 1984 toole", "1984 toole jj", "toole jj et al.", "jj et al. 1984", "et al. 1984 .", "al. 1984 . upon", "1984 . upon synthesis", "upon synthesis fviii", "synthesis fviii is", "fviii is translocated into", "is translocated into the", "translocated into the lumen", "into the lumen of", "the lumen of the", "lumen of the endoplasmic", "of the endoplasmic reticulum", "endoplasmic reticulum er", "er where", "where it undergoes extensive", "it undergoes extensive processing", "undergoes extensive processing including", "extensive processing including cleavage", "processing including cleavage of", "including cleavage of a", "cleavage of a signal", "of a signal peptide", "a signal peptide and", "signal peptide and n", "peptide and n linked", "and n linked glycosylation", "n linked glycosylation at", "linked glycosylation at asparagine", "glycosylation at asparagine residues", "asparagine residues kaufman", "residues kaufman rj", "kaufman rj et al.", "rj et al. 1988", "al. 1988 1997", "1997 kaufman rj", "kaufman rj 1998 .", "rj 1998 . in", "1998 . in the", ". in the er", "in the er lumen", "the er lumen of", "er lumen of mammalian", "lumen of mammalian cells", "of mammalian cells fviii", "mammalian cells fviii interacts", "cells fviii interacts with", "fviii interacts with the", "interacts with the protein", "with the protein chaperones", "the protein chaperones calnexin", "chaperones calnexin cnx", "cnx calreticulin", "crt and", "and immunoglobulin binding protein", "binding protein bip", "protein bip or", "or grp78 that", "grp78 that facilitate", "that facilitate proper folding", "facilitate proper folding of", "proper folding of proteins", "folding of proteins prior", "of proteins prior to", "proteins prior to trafficking", "prior to trafficking to", "to trafficking to the", "trafficking to the golgi", "to the golgi compartment", "golgi compartment marquette", "compartment marquette ka", "marquette ka et al.", "ka et al. 1995", "al. 1995 swaroop", "1995 swaroop m", "swaroop m et al.", "m et al. 1997", "al. 1997 pipe", "1997 pipe sw", "pipe sw et al.", "sw et al. 1998", "al. 1998 kaufman", "1998 kaufman rj", "rj et al. 1997", "al. 1997 kaufman", "rj 1998 . trafficking", "1998 . trafficking from", ". trafficking from the", "trafficking from the er", "from the er to", "the er to the", "er to the golgi", "the golgi compartment is", "golgi compartment is facilitated", "compartment is facilitated by", "is facilitated by lman1", "facilitated by lman1 and", "by lman1 and multiple", "lman1 and multiple combined", "and multiple combined factor", "multiple combined factor deficiency", "combined factor deficiency 2", "deficiency 2 mcfd2", "mcfd2 cargo receptor", "receptor complex zhang", "complex zhang b", "zhang b et al.", "b et al. 2005", "al. 2005 zheng", "zheng c et", "c et al. 2010", "al. 2010 2013", "2010 2013 .", "2013 . within the", ". within the golgi", "within the golgi apparatus", "golgi apparatus fviii", "apparatus fviii is", "fviii is subject to", "is subject to further", "subject to further processing", "further processing including", "processing including modification", "including modification of the", "modification of the n", "of the n linked", "the n linked oligosaccharides", "n linked oligosaccharides to", "linked oligosaccharides to complex", "oligosaccharides to complex type", "to complex type structures", "type structures o", "structures o linked", "linked glycosylation and", "glycosylation and sulfation", "and sulfation of specific", "sulfation of specific tyr", "of specific tyr residues", "tyr residues kaufman", "rj 1998 . upon", "1998 . upon secretion", ". upon secretion from", "upon secretion from the", "secretion from the cell", "the cell fviii", "cell fviii is", "fviii is cleaved at", "is cleaved at two", "cleaved at two sites", "at two sites in", "two sites in the", "sites in the b", "in the b domain", "the b domain to", "b domain to form", "domain to form a", "to form a heterodimer", "form a heterodimer consisting", "a heterodimer consisting of", "heterodimer consisting of the", "consisting of the heavy", "of the heavy chain", "the heavy chain containing", "heavy chain containing the", "chain containing the a1", "containing the a1 a2", "the a1 a2 b", "a1 a2 b domains", "a2 b domains in", "b domains in a", "domains in a metal", "in a metal ion", "a metal ion dependent", "metal ion dependent complex", "ion dependent complex with", "dependent complex with the", "complex with the light", "with the light chain", "the light chain consisting", "light chain consisting of", "chain consisting of the", "consisting of the a3", "of the a3 c1", "the a3 c1 c2", "a3 c1 c2 domains", "c2 domains kaufman", "domains kaufman rj", "kaufman rj 1998 .

              the", "rj 1998 .

              the reactome", "1998 .

              the reactome event", ".

              the reactome event describes", "reactome event describes defects", "event describes defects within", "describes defects within the", "defects within the secretory", "within the secretory pathway", "the secretory pathway due", "secretory pathway due to", "pathway due to mutations", "due to mutations in", "to mutations in the", "mutations in the f8", "the f8 gene that", "f8 gene that can", "gene that can impair", "that can impair fviii", "can impair fviii synthesis", "fviii synthesis folding", "folding intracellular processing", "intracellular processing and transport", "processing and transport which", "and transport which result", "transport which result in", "which result in a", "result in a lack", "in a lack or", "a lack or reduced", "lack or reduced levels", "or reduced levels of", "reduced levels of the", "levels of the plasma", "of the plasma fviii", "the plasma fviii protein.", "plasma fviii protein. the", "fviii protein. the module", "protein. the module includes", "the module includes also", "module includes also an", "includes also an event", "also an event of", "an event of defective", "event of defective post", "of defective post translational", "defective post translational tyrosine", "post translational tyrosine sulfonation", "translational tyrosine sulfonation of", "tyrosine sulfonation of fviii", "sulfonation of fviii in", "of fviii in the", "fviii in the golgi", "in the golgi apparatus", "the golgi apparatus that", "golgi apparatus that is", "apparatus that is required", "that is required for", "is required for the", "required for the optimal", "for the optimal interaction", "the optimal interaction between", "optimal interaction between the", "interaction between the secreted", "between the secreted fviii", "the secreted fviii and", "secreted fviii and the", "fviii and the von", "and the von willebrand", "the von willebrand factor", "willebrand factor vwf", "factor vwf .", "a ha is", "ha is a bleeding", "is a bleeding disorder caused", "a bleeding disorder caused by", "bleeding disorder caused by lack", "disorder caused by lack of", "caused by lack of or", "by lack of or a", "lack of or a defective", "of or a defective factor", "or a defective factor viii", "defective factor viii fviii", "viii fviii protein", "fviii protein and results", "protein and results from defects", "and results from defects in", "results from defects in the", "from defects in the f8", "defects in the f8 gene", "the f8 gene peyvandi", "f8 gene peyvandi f", "gene peyvandi f et", "peyvandi f et al. 2016", "f et al. 2016 .

              in", "et al. 2016 .

              in healthy", "al. 2016 .

              in healthy individuals", ".

              in healthy individuals fviii", "healthy individuals fviii is", "individuals fviii is synthesized", "fviii is synthesized as a", "is synthesized as a large", "synthesized as a large glycoprotein", "as a large glycoprotein of", "a large glycoprotein of 2351", "large glycoprotein of 2351 amino", "glycoprotein of 2351 amino acids", "of 2351 amino acids with", "2351 amino acids with a", "amino acids with a discrete", "acids with a discrete domain", "with a discrete domain structure:", "a discrete domain structure: a1", "discrete domain structure: a1 a2", "domain structure: a1 a2 b", "structure: a1 a2 b a3", "a1 a2 b a3 c1", "a2 b a3 c1 c2", "a3 c1 c2 wood", "c1 c2 wood wi", "c2 wood wi et", "wood wi et al. 1984", "et al. 1984 vehar", "al. 1984 vehar ga", "1984 vehar ga et", "vehar ga et al. 1984", "et al. 1984 toole", "al. 1984 toole jj", "1984 toole jj et", "toole jj et al. 1984", "jj et al. 1984 .", "et al. 1984 . upon", "al. 1984 . upon synthesis", ". upon synthesis fviii", "upon synthesis fviii is", "synthesis fviii is translocated", "fviii is translocated into the", "is translocated into the lumen", "translocated into the lumen of", "into the lumen of the", "the lumen of the endoplasmic", "lumen of the endoplasmic reticulum", "the endoplasmic reticulum er", "er where it", "where it undergoes extensive processing", "it undergoes extensive processing including", "undergoes extensive processing including cleavage", "extensive processing including cleavage of", "processing including cleavage of a", "including cleavage of a signal", "cleavage of a signal peptide", "of a signal peptide and", "a signal peptide and n", "signal peptide and n linked", "peptide and n linked glycosylation", "and n linked glycosylation at", "n linked glycosylation at asparagine", "linked glycosylation at asparagine residues", "at asparagine residues kaufman", "asparagine residues kaufman rj", "residues kaufman rj et", "kaufman rj et al. 1988", "et al. 1988 1997", "1988 1997 kaufman", "1997 kaufman rj 1998", "kaufman rj 1998 . in", "rj 1998 . in the", "1998 . in the er", ". in the er lumen", "in the er lumen of", "the er lumen of mammalian", "er lumen of mammalian cells", "lumen of mammalian cells fviii", "of mammalian cells fviii interacts", "mammalian cells fviii interacts with", "cells fviii interacts with the", "fviii interacts with the protein", "interacts with the protein chaperones", "with the protein chaperones calnexin", "protein chaperones calnexin cnx", "crt and immunoglobulin", "immunoglobulin binding protein bip", "binding protein bip or", "protein bip or grp78", "bip or grp78 that", "or grp78 that facilitate", "grp78 that facilitate proper", "that facilitate proper folding of", "facilitate proper folding of proteins", "proper folding of proteins prior", "folding of proteins prior to", "of proteins prior to trafficking", "proteins prior to trafficking to", "prior to trafficking to the", "to trafficking to the golgi", "trafficking to the golgi compartment", "the golgi compartment marquette", "golgi compartment marquette ka", "compartment marquette ka et", "marquette ka et al. 1995", "et al. 1995 swaroop", "al. 1995 swaroop m", "1995 swaroop m et", "swaroop m et al. 1997", "et al. 1997 pipe", "al. 1997 pipe sw", "1997 pipe sw et", "pipe sw et al. 1998", "et al. 1998 kaufman", "al. 1998 kaufman rj", "1998 kaufman rj et", "kaufman rj et al. 1997", "et al. 1997 kaufman", "al. 1997 kaufman rj", "kaufman rj 1998 . trafficking", "rj 1998 . trafficking from", "1998 . trafficking from the", ". trafficking from the er", "trafficking from the er to", "from the er to the", "the er to the golgi", "er to the golgi compartment", "to the golgi compartment is", "the golgi compartment is facilitated", "golgi compartment is facilitated by", "compartment is facilitated by lman1", "is facilitated by lman1 and", "facilitated by lman1 and multiple", "by lman1 and multiple combined", "lman1 and multiple combined factor", "and multiple combined factor deficiency", "multiple combined factor deficiency 2", "factor deficiency 2 mcfd2", "2 mcfd2 cargo", "mcfd2 cargo receptor complex", "cargo receptor complex zhang", "receptor complex zhang b", "complex zhang b et", "zhang b et al. 2005", "et al. 2005 zheng", "2005 zheng c", "zheng c et al.", "et al. 2010 2013", "al. 2010 2013 .", "2010 2013 . within", "2013 . within the golgi", ". within the golgi apparatus", "the golgi apparatus fviii", "golgi apparatus fviii is", "apparatus fviii is subject", "fviii is subject to further", "is subject to further processing", "to further processing including", "further processing including modification", "processing including modification of", "including modification of the n", "modification of the n linked", "of the n linked oligosaccharides", "the n linked oligosaccharides to", "n linked oligosaccharides to complex", "linked oligosaccharides to complex type", "oligosaccharides to complex type structures", "complex type structures o", "type structures o linked", "structures o linked glycosylation", "o linked glycosylation and", "linked glycosylation and sulfation", "glycosylation and sulfation of", "and sulfation of specific tyr", "sulfation of specific tyr residues", "specific tyr residues kaufman", "tyr residues kaufman rj", "residues kaufman rj 1998", "kaufman rj 1998 . upon", "rj 1998 . upon secretion", "1998 . upon secretion from", ". upon secretion from the", "upon secretion from the cell", "from the cell fviii", "the cell fviii is", "cell fviii is cleaved", "fviii is cleaved at two", "is cleaved at two sites", "cleaved at two sites in", "at two sites in the", "two sites in the b", "sites in the b domain", "in the b domain to", "the b domain to form", "b domain to form a", "domain to form a heterodimer", "to form a heterodimer consisting", "form a heterodimer consisting of", "a heterodimer consisting of the", "heterodimer consisting of the heavy", "consisting of the heavy chain", "of the heavy chain containing", "the heavy chain containing the", "heavy chain containing the a1", "chain containing the a1 a2", "containing the a1 a2 b", "the a1 a2 b domains", "a1 a2 b domains in", "a2 b domains in a", "b domains in a metal", "domains in a metal ion", "in a metal ion dependent", "a metal ion dependent complex", "metal ion dependent complex with", "ion dependent complex with the", "dependent complex with the light", "complex with the light chain", "with the light chain consisting", "the light chain consisting of", "light chain consisting of the", "chain consisting of the a3", "consisting of the a3 c1", "of the a3 c1 c2", "the a3 c1 c2 domains", "c1 c2 domains kaufman", "c2 domains kaufman rj", "domains kaufman rj et", "kaufman rj 1998 .

              the reactome", "rj 1998 .

              the reactome event", "1998 .

              the reactome event describes", ".

              the reactome event describes defects", "reactome event describes defects within", "event describes defects within the", "describes defects within the secretory", "defects within the secretory pathway", "within the secretory pathway due", "the secretory pathway due to", "secretory pathway due to mutations", "pathway due to mutations in", "due to mutations in the", "to mutations in the f8", "mutations in the f8 gene", "in the f8 gene that", "the f8 gene that can", "f8 gene that can impair", "gene that can impair fviii", "that can impair fviii synthesis", "impair fviii synthesis folding", "synthesis folding intracellular", "folding intracellular processing and", "intracellular processing and transport which", "processing and transport which result", "and transport which result in", "transport which result in a", "which result in a lack", "result in a lack or", "in a lack or reduced", "a lack or reduced levels", "lack or reduced levels of", "or reduced levels of the", "reduced levels of the plasma", "levels of the plasma fviii", "of the plasma fviii protein.", "the plasma fviii protein. the", "plasma fviii protein. the module", "fviii protein. the module includes", "protein. the module includes also", "the module includes also an", "module includes also an event", "includes also an event of", "also an event of defective", "an event of defective post", "event of defective post translational", "of defective post translational tyrosine", "defective post translational tyrosine sulfonation", "post translational tyrosine sulfonation of", "translational tyrosine sulfonation of fviii", "tyrosine sulfonation of fviii in", "sulfonation of fviii in the", "of fviii in the golgi", "fviii in the golgi apparatus", "in the golgi apparatus that", "the golgi apparatus that is", "golgi apparatus that is required", "apparatus that is required for", "that is required for the", "is required for the optimal", "required for the optimal interaction", "for the optimal interaction between", "the optimal interaction between the", "optimal interaction between the secreted", "interaction between the secreted fviii", "between the secreted fviii and", "the secreted fviii and the", "secreted fviii and the von", "fviii and the von willebrand", "and the von willebrand factor", "von willebrand factor vwf", "willebrand factor vwf ." ] }, { "record_id": "GLY_000594_1_1996", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9679504", "r hsa", "hsa 9679504", "r hsa 9679504" ] }, { "record_id": "GLY_000594_1_1996", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "translation of", "of replicase", "replicase and", "and assembly", "assembly of", "of the", "the replication", "replication transcription", "transcription complex", "translation of replicase", "of replicase and", "replicase and assembly", "and assembly of", "assembly of the", "of the replication", "the replication transcription", "replication transcription complex", "translation of replicase and", "of replicase and assembly", "replicase and assembly of", "and assembly of the", "assembly of the replication", "of the replication transcription", "the replication transcription complex", "translation of replicase and assembly", "of replicase and assembly of", "replicase and assembly of the", "and assembly of the replication", "assembly of the replication transcription", "of the replication transcription complex", "after entry", "entry and", "and uncoating", "the sars", "sars cov", "cov 1", "1 genomic", "genomic rna", "rna serves", "serves as", "as a", "a transcript", "transcript to", "to allow", "allow cap", "cap dependent", "dependent translation", "of orf1a", "orf1a to", "to produce", "produce polyprotein", "polyprotein pp1a.", "pp1a. a", "a slippery", "slippery sequence", "sequence and", "and an", "an rna", "rna pseudoknot", "pseudoknot near", "near the", "the end", "end of", "orf1a enable", "enable 25", "30% of", "the ribosomes", "ribosomes to", "to undergo", "1 frameshifting", "to continue", "continue translation", "of orf1b", "orf1b to", "produce a", "a longer", "longer polyprotein", "polyprotein pp1ab.", "pp1ab. the", "the autoproteolytic", "autoproteolytic cleavage", "cleavage of", "of pp1a", "pp1a and", "and pp1ab", "pp1ab generates", "generates 15", "15 16", "16 nonstructural", "nonstructural proteins", "with various", "various functions.", "functions. the", "the rna", "rna dependent", "dependent rna", "rna polymerase", "activity is", "is encoded", "encoded in", "in nsp12", "and papain", "papain like", "like protease", "and main", "main protease", "activities are", "are encoded", "in nsp3", "nsp3 and", "and nsp5", "respectively. nsp3", "and 6", "6 induce", "induce rearrangement", "rearrangement of", "the cellular", "cellular membrane", "membrane to", "to form", "form double", "double membrane", "membrane vesicles", "where the", "the coronavirus", "coronavirus replication", "is assembled", "assembled and", "and anchored.

              programmed", "anchored.

              programmed ribosomal", "ribosomal frameshifting", "may be", "be regulated", "regulated by", "by viral", "viral or", "or host", "host factors", "factors in", "in addition", "addition to", "to viral", "viral rna", "rna secondary", "secondary structures.", "structures. for", "for example", "prf in", "in the", "the related", "related arterivirus", "arterivirus porcine", "porcine reproductive", "reproductive and", "and respiratory", "respiratory syndrome", "syndrome virus", "is transactivated", "transactivated by", "by the", "the viral", "viral protein", "protein nsp1", "which interacts", "interacts with", "with the", "the prf", "prf signal", "signal via", "via a", "a putative", "putative rna", "rna binding", "binding motif.", "motif. a", "a host", "host rna", "binding protein", "protein called", "called annexin", "annexin a2", "binds the", "the pseudoknot", "pseudoknot structure", "structure in", "the ibv", "ibv genome.", "genome. host", "the early", "early secretory", "secretory pathway", "pathway appear", "appear to", "to be", "be involved", "involved in", "in dmv", "dmv formation", "formation and", "and rtc", "rtc assembly:", "assembly: golgi", "golgi specific", "specific brefeldin", "brefeldin a", "a resistance", "resistance guanine", "guanine nucleotide", "nucleotide exchange", "exchange factor", "factor 1", "and its", "its effector", "effector adp", "adp ribosylation", "ribosylation factor", "are both", "both required", "required for", "for normal", "normal dmv", "and efficient", "efficient rna", "rna replication", "replication of", "of mouse", "mouse hepatitis", "hepatitis virus", "a prototypic", "prototypic betacoronavirus", "betacoronavirus that", "that infects", "infects mice", "fung &", "& liu", "liu 2019", "2019 .

              ", "after entry and", "entry and uncoating", "uncoating the", "the sars cov", "sars cov 1", "cov 1 genomic", "1 genomic rna", "genomic rna serves", "rna serves as", "serves as a", "as a transcript", "a transcript to", "transcript to allow", "to allow cap", "allow cap dependent", "cap dependent translation", "dependent translation of", "translation of orf1a", "of orf1a to", "orf1a to produce", "to produce polyprotein", "produce polyprotein pp1a.", "polyprotein pp1a. a", "pp1a. a slippery", "a slippery sequence", "slippery sequence and", "sequence and an", "and an rna", "an rna pseudoknot", "rna pseudoknot near", "pseudoknot near the", "near the end", "the end of", "end of orf1a", "of orf1a enable", "orf1a enable 25", "30% of the", "of the ribosomes", "the ribosomes to", "ribosomes to undergo", "undergo 1", "frameshifting to", "to continue translation", "continue translation of", "translation of orf1b", "of orf1b to", "orf1b to produce", "to produce a", "produce a longer", "a longer polyprotein", "longer polyprotein pp1ab.", "polyprotein pp1ab. the", "pp1ab. the autoproteolytic", "the autoproteolytic cleavage", "autoproteolytic cleavage of", "cleavage of pp1a", "of pp1a and", "pp1a and pp1ab", "and pp1ab generates", "pp1ab generates 15", "generates 15 16", "15 16 nonstructural", "16 nonstructural proteins", "proteins nsps", "nsps with", "with various functions.", "various functions. the", "functions. the rna", "the rna dependent", "rna dependent rna", "dependent rna polymerase", "polymerase rdrp", "rdrp activity", "activity is encoded", "is encoded in", "encoded in nsp12", "nsp12 and", "and papain like", "papain like protease", "protease plpro", "plpro and", "and main protease", "protease mpro", "mpro activities", "activities are encoded", "are encoded in", "encoded in nsp3", "in nsp3 and", "nsp3 and nsp5", "nsp5 respectively.", "nsp3 4", "4 and", "and 6 induce", "6 induce rearrangement", "induce rearrangement of", "rearrangement of the", "of the cellular", "the cellular membrane", "cellular membrane to", "membrane to form", "to form double", "form double membrane", "double membrane vesicles", "vesicles dmvs", "dmvs where", "where the coronavirus", "the coronavirus replication", "coronavirus replication transcription", "complex rtc", "rtc is", "is assembled and", "assembled and anchored.

              programmed", "and anchored.

              programmed ribosomal", "anchored.

              programmed ribosomal frameshifting", "frameshifting prf", "prf may", "may be regulated", "be regulated by", "regulated by viral", "by viral or", "viral or host", "or host factors", "host factors in", "factors in addition", "in addition to", "addition to viral", "to viral rna", "viral rna secondary", "rna secondary structures.", "secondary structures. for", "structures. for example", "example prf", "prf in the", "in the related", "the related arterivirus", "related arterivirus porcine", "arterivirus porcine reproductive", "porcine reproductive and", "reproductive and respiratory", "and respiratory syndrome", "respiratory syndrome virus", "virus prrsv", "prrsv is", "is transactivated by", "transactivated by the", "by the viral", "the viral protein", "viral protein nsp1", "nsp1 which", "which interacts with", "interacts with the", "with the prf", "the prf signal", "prf signal via", "signal via a", "via a putative", "a putative rna", "putative rna binding", "rna binding motif.", "binding motif. a", "motif. a host", "a host rna", "host rna binding", "rna binding protein", "binding protein called", "protein called annexin", "called annexin a2", "a2 anxa2", "anxa2 binds", "binds the pseudoknot", "the pseudoknot structure", "pseudoknot structure in", "structure in the", "in the ibv", "the ibv genome.", "ibv genome. host", "genome. host factors", "factors in the", "in the early", "the early secretory", "early secretory pathway", "secretory pathway appear", "pathway appear to", "appear to be", "to be involved", "be involved in", "involved in dmv", "in dmv formation", "dmv formation and", "formation and rtc", "and rtc assembly:", "rtc assembly: golgi", "assembly: golgi specific", "golgi specific brefeldin", "specific brefeldin a", "brefeldin a resistance", "a resistance guanine", "resistance guanine nucleotide", "guanine nucleotide exchange", "nucleotide exchange factor", "exchange factor 1", "1 gbf1", "gbf1 and", "and its effector", "its effector adp", "effector adp ribosylation", "adp ribosylation factor", "ribosylation factor 1", "1 arf1", "arf1 are", "are both required", "both required for", "required for normal", "for normal dmv", "normal dmv formation", "formation and efficient", "and efficient rna", "efficient rna replication", "rna replication of", "replication of mouse", "of mouse hepatitis", "mouse hepatitis virus", "virus mhv", "a prototypic betacoronavirus", "prototypic betacoronavirus that", "betacoronavirus that infects", "that infects mice", "mice fung", "fung & liu", "& liu 2019", "liu 2019 .

              ", "after entry and uncoating", "and uncoating the", "uncoating the sars", "the sars cov 1", "sars cov 1 genomic", "cov 1 genomic rna", "1 genomic rna serves", "genomic rna serves as", "rna serves as a", "serves as a transcript", "as a transcript to", "a transcript to allow", "transcript to allow cap", "to allow cap dependent", "allow cap dependent translation", "cap dependent translation of", "dependent translation of orf1a", "translation of orf1a to", "of orf1a to produce", "orf1a to produce polyprotein", "to produce polyprotein pp1a.", "produce polyprotein pp1a. a", "polyprotein pp1a. a slippery", "pp1a. a slippery sequence", "a slippery sequence and", "slippery sequence and an", "sequence and an rna", "and an rna pseudoknot", "an rna pseudoknot near", "rna pseudoknot near the", "pseudoknot near the end", "near the end of", "the end of orf1a", "end of orf1a enable", "of orf1a enable 25", "25 30%", "30% of the ribosomes", "of the ribosomes to", "the ribosomes to undergo", "to undergo 1", "undergo 1 frameshifting", "1 frameshifting to", "frameshifting to continue", "to continue translation of", "continue translation of orf1b", "translation of orf1b to", "of orf1b to produce", "orf1b to produce a", "to produce a longer", "produce a longer polyprotein", "a longer polyprotein pp1ab.", "longer polyprotein pp1ab. the", "polyprotein pp1ab. the autoproteolytic", "pp1ab. the autoproteolytic cleavage", "the autoproteolytic cleavage of", "autoproteolytic cleavage of pp1a", "cleavage of pp1a and", "of pp1a and pp1ab", "pp1a and pp1ab generates", "and pp1ab generates 15", "pp1ab generates 15 16", "generates 15 16 nonstructural", "15 16 nonstructural proteins", "nonstructural proteins nsps", "nsps with various", "with various functions. the", "various functions. the rna", "functions. the rna dependent", "the rna dependent rna", "rna dependent rna polymerase", "rna polymerase rdrp", "rdrp activity is", "activity is encoded in", "is encoded in nsp12", "in nsp12 and", "nsp12 and papain", "and papain like protease", "like protease plpro", "plpro and main", "main protease mpro", "mpro activities are", "activities are encoded in", "are encoded in nsp3", "encoded in nsp3 and", "in nsp3 and nsp5", "and nsp5 respectively.", "nsp5 respectively. nsp3", "respectively. nsp3 4", "4 and 6", "and 6 induce rearrangement", "6 induce rearrangement of", "induce rearrangement of the", "rearrangement of the cellular", "of the cellular membrane", "the cellular membrane to", "cellular membrane to form", "membrane to form double", "to form double membrane", "form double membrane vesicles", "membrane vesicles dmvs", "dmvs where the", "where the coronavirus replication", "the coronavirus replication transcription", "coronavirus replication transcription complex", "transcription complex rtc", "rtc is assembled", "is assembled and anchored.

              programmed", "assembled and anchored.

              programmed ribosomal", "and anchored.

              programmed ribosomal frameshifting", "ribosomal frameshifting prf", "prf may be", "may be regulated by", "be regulated by viral", "regulated by viral or", "by viral or host", "viral or host factors", "or host factors in", "host factors in addition", "factors in addition to", "in addition to viral", "addition to viral rna", "to viral rna secondary", "viral rna secondary structures.", "rna secondary structures. for", "secondary structures. for example", "for example prf", "example prf in", "prf in the related", "in the related arterivirus", "the related arterivirus porcine", "related arterivirus porcine reproductive", "arterivirus porcine reproductive and", "porcine reproductive and respiratory", "reproductive and respiratory syndrome", "and respiratory syndrome virus", "syndrome virus prrsv", "prrsv is transactivated", "is transactivated by the", "transactivated by the viral", "by the viral protein", "the viral protein nsp1", "protein nsp1 which", "nsp1 which interacts", "which interacts with the", "interacts with the prf", "with the prf signal", "the prf signal via", "prf signal via a", "signal via a putative", "via a putative rna", "a putative rna binding", "putative rna binding motif.", "rna binding motif. a", "binding motif. a host", "motif. a host rna", "a host rna binding", "host rna binding protein", "rna binding protein called", "binding protein called annexin", "protein called annexin a2", "annexin a2 anxa2", "anxa2 binds the", "binds the pseudoknot structure", "the pseudoknot structure in", "pseudoknot structure in the", "structure in the ibv", "in the ibv genome.", "the ibv genome. host", "ibv genome. host factors", "genome. host factors in", "host factors in the", "factors in the early", "in the early secretory", "the early secretory pathway", "early secretory pathway appear", "secretory pathway appear to", "pathway appear to be", "appear to be involved", "to be involved in", "be involved in dmv", "involved in dmv formation", "in dmv formation and", "dmv formation and rtc", "formation and rtc assembly:", "and rtc assembly: golgi", "rtc assembly: golgi specific", "assembly: golgi specific brefeldin", "golgi specific brefeldin a", "specific brefeldin a resistance", "brefeldin a resistance guanine", "a resistance guanine nucleotide", "resistance guanine nucleotide exchange", "guanine nucleotide exchange factor", "nucleotide exchange factor 1", "factor 1 gbf1", "gbf1 and its", "and its effector adp", "its effector adp ribosylation", "effector adp ribosylation factor", "adp ribosylation factor 1", "factor 1 arf1", "arf1 are both", "are both required for", "both required for normal", "required for normal dmv", "for normal dmv formation", "normal dmv formation and", "dmv formation and efficient", "formation and efficient rna", "and efficient rna replication", "efficient rna replication of", "rna replication of mouse", "replication of mouse hepatitis", "of mouse hepatitis virus", "hepatitis virus mhv", "mhv a", "a prototypic betacoronavirus that", "prototypic betacoronavirus that infects", "betacoronavirus that infects mice", "infects mice fung", "mice fung &", "fung & liu 2019", "& liu 2019 .

              ", "entry and uncoating the", "and uncoating the sars", "uncoating the sars cov", "the sars cov 1 genomic", "sars cov 1 genomic rna", "cov 1 genomic rna serves", "1 genomic rna serves as", "genomic rna serves as a", "rna serves as a transcript", "serves as a transcript to", "as a transcript to allow", "a transcript to allow cap", "transcript to allow cap dependent", "to allow cap dependent translation", "allow cap dependent translation of", "cap dependent translation of orf1a", "dependent translation of orf1a to", "translation of orf1a to produce", "of orf1a to produce polyprotein", "orf1a to produce polyprotein pp1a.", "to produce polyprotein pp1a. a", "produce polyprotein pp1a. a slippery", "polyprotein pp1a. a slippery sequence", "pp1a. a slippery sequence and", "a slippery sequence and an", "slippery sequence and an rna", "sequence and an rna pseudoknot", "and an rna pseudoknot near", "an rna pseudoknot near the", "rna pseudoknot near the end", "pseudoknot near the end of", "near the end of orf1a", "the end of orf1a enable", "end of orf1a enable 25", "enable 25 30%", "25 30% of", "30% of the ribosomes to", "of the ribosomes to undergo", "ribosomes to undergo 1", "to undergo 1 frameshifting", "1 frameshifting to continue", "frameshifting to continue translation", "to continue translation of orf1b", "continue translation of orf1b to", "translation of orf1b to produce", "of orf1b to produce a", "orf1b to produce a longer", "to produce a longer polyprotein", "produce a longer polyprotein pp1ab.", "a longer polyprotein pp1ab. the", "longer polyprotein pp1ab. the autoproteolytic", "polyprotein pp1ab. the autoproteolytic cleavage", "pp1ab. the autoproteolytic cleavage of", "the autoproteolytic cleavage of pp1a", "autoproteolytic cleavage of pp1a and", "cleavage of pp1a and pp1ab", "of pp1a and pp1ab generates", "pp1a and pp1ab generates 15", "and pp1ab generates 15 16", "pp1ab generates 15 16 nonstructural", "generates 15 16 nonstructural proteins", "16 nonstructural proteins nsps", "proteins nsps with", "nsps with various functions.", "with various functions. the rna", "various functions. the rna dependent", "functions. the rna dependent rna", "the rna dependent rna polymerase", "dependent rna polymerase rdrp", "polymerase rdrp activity", "rdrp activity is encoded", "activity is encoded in nsp12", "encoded in nsp12 and", "in nsp12 and papain", "nsp12 and papain like", "papain like protease plpro", "protease plpro and", "plpro and main protease", "and main protease mpro", "protease mpro activities", "mpro activities are encoded", "activities are encoded in nsp3", "are encoded in nsp3 and", "encoded in nsp3 and nsp5", "nsp3 and nsp5 respectively.", "and nsp5 respectively. nsp3", "nsp3 4 and", "4 and 6 induce", "and 6 induce rearrangement of", "6 induce rearrangement of the", "induce rearrangement of the cellular", "rearrangement of the cellular membrane", "of the cellular membrane to", "the cellular membrane to form", "cellular membrane to form double", "membrane to form double membrane", "to form double membrane vesicles", "double membrane vesicles dmvs", "vesicles dmvs where", "dmvs where the coronavirus", "where the coronavirus replication transcription", "the coronavirus replication transcription complex", "replication transcription complex rtc", "complex rtc is", "rtc is assembled and", "is assembled and anchored.

              programmed ribosomal", "assembled and anchored.

              programmed ribosomal frameshifting", "anchored.

              programmed ribosomal frameshifting prf", "frameshifting prf may", "prf may be regulated", "may be regulated by viral", "be regulated by viral or", "regulated by viral or host", "by viral or host factors", "viral or host factors in", "or host factors in addition", "host factors in addition to", "factors in addition to viral", "in addition to viral rna", "addition to viral rna secondary", "to viral rna secondary structures.", "viral rna secondary structures. for", "rna secondary structures. for example", "structures. for example prf", "for example prf in", "example prf in the", "prf in the related arterivirus", "in the related arterivirus porcine", "the related arterivirus porcine reproductive", "related arterivirus porcine reproductive and", "arterivirus porcine reproductive and respiratory", "porcine reproductive and respiratory syndrome", "reproductive and respiratory syndrome virus", "respiratory syndrome virus prrsv", "virus prrsv is", "prrsv is transactivated by", "is transactivated by the viral", "transactivated by the viral protein", "by the viral protein nsp1", "viral protein nsp1 which", "protein nsp1 which interacts", "nsp1 which interacts with", "which interacts with the prf", "interacts with the prf signal", "with the prf signal via", "the prf signal via a", "prf signal via a putative", "signal via a putative rna", "via a putative rna binding", "a putative rna binding motif.", "putative rna binding motif. a", "rna binding motif. a host", "binding motif. a host rna", "motif. a host rna binding", "a host rna binding protein", "host rna binding protein called", "rna binding protein called annexin", "binding protein called annexin a2", "called annexin a2 anxa2", "a2 anxa2 binds", "anxa2 binds the pseudoknot", "binds the pseudoknot structure in", "the pseudoknot structure in the", "pseudoknot structure in the ibv", "structure in the ibv genome.", "in the ibv genome. host", "the ibv genome. host factors", "ibv genome. host factors in", "genome. host factors in the", "host factors in the early", "factors in the early secretory", "in the early secretory pathway", "the early secretory pathway appear", "early secretory pathway appear to", "secretory pathway appear to be", "pathway appear to be involved", "appear to be involved in", "to be involved in dmv", "be involved in dmv formation", "involved in dmv formation and", "in dmv formation and rtc", "dmv formation and rtc assembly:", "formation and rtc assembly: golgi", "and rtc assembly: golgi specific", "rtc assembly: golgi specific brefeldin", "assembly: golgi specific brefeldin a", "golgi specific brefeldin a resistance", "specific brefeldin a resistance guanine", "brefeldin a resistance guanine nucleotide", "a resistance guanine nucleotide exchange", "resistance guanine nucleotide exchange factor", "guanine nucleotide exchange factor 1", "exchange factor 1 gbf1", "1 gbf1 and", "gbf1 and its effector", "and its effector adp ribosylation", "its effector adp ribosylation factor", "effector adp ribosylation factor 1", "ribosylation factor 1 arf1", "1 arf1 are", "arf1 are both required", "are both required for normal", "both required for normal dmv", "required for normal dmv formation", "for normal dmv formation and", "normal dmv formation and efficient", "dmv formation and efficient rna", "formation and efficient rna replication", "and efficient rna replication of", "efficient rna replication of mouse", "rna replication of mouse hepatitis", "replication of mouse hepatitis virus", "mouse hepatitis virus mhv", "mhv a prototypic", "a prototypic betacoronavirus that infects", "prototypic betacoronavirus that infects mice", "that infects mice fung", "infects mice fung &", "mice fung & liu", "fung & liu 2019 .

              " ] }, { "record_id": "GLY_000594_1_1997", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9664323", "r hsa", "hsa 9664323", "r hsa 9664323" ] }, { "record_id": "GLY_000594_1_1997", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fcgr3a mediated", "mediated il10", "il10 synthesis", "fcgr3a mediated il10", "mediated il10 synthesis", "fcgr3a mediated il10 synthesis", "interleukin 10", "il 10", "is an", "an important", "important immunoregulatory", "immunoregulatory cytokine", "cytokine produced", "produced by", "by many", "many cell", "cell populations", "in macrophages", "macrophages it", "it is", "is induced", "induced after", "after the", "the stimulation", "stimulation of", "of tlrs", "fc\u03b3 receptors", "receptors or", "or by", "by the", "the tlr", "tlr fc\u03b3r", "fc\u03b3r crosstalk", "vogelpoel et", "et al.", "al. 2014", "2014 &", "& saninet", "saninet al.", "al. 2015", "2015 .", ". classically", "its function", "function is", "is considered", "considered to", "to be", "be the", "the limitation", "limitation and", "and termination", "termination of", "of inflammatory", "inflammatory responses", "responses and", "and the", "the regulation", "regulation of", "of differentiation", "differentiation of", "of several", "several immune", "immune cells", "asadullah et", "al. 2003", "2003 .", ". there", "there is", "is increasing", "increasing evidence", "evidence of", "of the", "the role", "role of", "of il", "10 in", "in parasite", "parasite infection", "infection outcomes", "outcomes either", "either as", "as a", "a protective", "protective or", "or a", "a pathological", "pathological mediator", ". in", "in the", "the context", "context of", "the parasitic", "parasitic disease", "disease cutaneous", "cutaneous leishmaniasis", "leishmania amastigotes", "amastigotes opsonized", "opsonized by", "by igg", "igg induce", "induce il", "10 response", "response 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considered to", "considered to be", "to be the", "be the limitation", "the limitation and", "limitation and termination", "and termination of", "termination of inflammatory", "of inflammatory responses", "inflammatory responses and", "responses and the", "and the regulation", "the regulation of", "regulation of differentiation", "of differentiation of", "differentiation of several", "of several immune", "several immune cells", "cells asadullah", "asadullah et al.", "et al. 2003", "al. 2003 .", "2003 . there", ". there is", "there is increasing", "is increasing evidence", "increasing evidence of", "evidence of the", "of the role", "the role of", "role of il", "of il 10", "il 10 in", "10 in parasite", "in parasite infection", "parasite infection outcomes", "infection outcomes either", "outcomes either as", "either as a", "as a protective", "a protective or", "protective or a", "or a pathological", "a pathological mediator", "mediator asadullah", "2003 . in", ". in the", "in the context", 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"responses and the regulation", "and the regulation of", "the regulation of differentiation", "regulation of differentiation of", "of differentiation of several", "differentiation of several immune", "of several immune cells", "immune cells asadullah", "cells asadullah et", "asadullah et al. 2003", "et al. 2003 .", "al. 2003 . there", "2003 . there is", ". there is increasing", "there is increasing evidence", "is increasing evidence of", "increasing evidence of the", "evidence of the role", "of the role of", "the role of il", "role of il 10", "of il 10 in", "il 10 in parasite", "10 in parasite infection", "in parasite infection outcomes", "parasite infection outcomes either", "infection outcomes either as", "outcomes either as a", "either as a protective", "as a protective or", "a protective or a", "protective or a pathological", "or a pathological mediator", "pathological mediator asadullah", "mediator asadullah et", "al. 2003 . in", "2003 . in the", ". in the context", "in the 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immunoregulatory cytokine produced by", "immunoregulatory cytokine produced by many", "cytokine produced by many cell", "produced by many cell populations", "many cell populations in", "cell populations in macrophages", "populations in macrophages it", "in macrophages it is induced", "macrophages it is induced after", "it is induced after the", "is induced after the stimulation", "induced after the stimulation of", "after the stimulation of tlrs", "stimulation of tlrs fc\u03b3", "of tlrs fc\u03b3 receptors", "tlrs fc\u03b3 receptors or", "fc\u03b3 receptors or by the", "receptors or by the tlr", "or by the tlr fc\u03b3r", "by the tlr fc\u03b3r crosstalk", "tlr fc\u03b3r crosstalk vogelpoel", "fc\u03b3r crosstalk vogelpoel et", "crosstalk vogelpoel et al.", "vogelpoel et al. 2014 &", "et al. 2014 & saninet", "al. 2014 & saninet al.", "2014 & saninet al. 2015", "& saninet al. 2015 .", "saninet al. 2015 . classically", "2015 . classically its", ". classically its function", "classically 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"fcgr3a mediated", "mediated phagocytosis", "fcgr3a mediated phagocytosis", "the fc", "fc gamma", "gamma receptors", "have been", "been reported", "reported to", "to facilitate", "facilitate leishmania", "leishmania internalization", "especially when", "when in", "in its", "its amastigote", "amastigote form", "ueno et", "et al.", "al. 2012", "2012 .", ". following", "following cell", "cell to", "to cell", "cell propagation", "propagation within", "within an", "an established", "established infection", "infection or", "or reinfection", "reinfection of", "of a", "a previously", "previously infected", "infected host", "the igg", "igg produced", "produced by", "by the", "the host", "host covers", "covers the", "the surface", "surface of", "of leishmania", "leishmania amastigote", "amastigote parasites", "making them", "them more", "more susceptible", "susceptible to", "to phagocytosis", "phagocytosis through", "through fcgrs", "polando et", "al. 2013", "2013 .

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              classically", ".

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              classically", "2013 .

              classically phagocytosis", ".

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              classically", "al. 2013 .

              classically phagocytosis", "2013 .

              classically phagocytosis via", ".

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              the reduction of atp", ".

              the reduction of atp to", "reduction of atp to ade", "of atp to ade rib", "atp to ade rib is", "to ade rib is thought", "ade rib is thought to", "rib is thought to be", "is thought to be a", "thought to be a regulatory", "to be a regulatory mechanism", "be a regulatory mechanism by", "a regulatory mechanism by which", "regulatory mechanism by which the", "mechanism by which the synthesis", "by which the synthesis of", "which the synthesis of anti", "the synthesis of anti inflammatory", "synthesis of anti inflammatory cytokines", "of anti inflammatory cytokines is", "anti inflammatory cytokines is induced.", "inflammatory cytokines is induced. in", "cytokines is induced. in addition", "induced. in addition killing", "in addition killing mechanisms", "addition killing mechanisms are", "killing mechanisms are switched off", "are switched off figueiredo", "switched off figueiredo et", "off figueiredo et al.", "figueiredo et al. 2016 .", "et al. 2016 . accordingly", "2016 . accordingly increased", ". accordingly increased expression", "accordingly increased expression of", "increased expression of adora2b in", "expression of adora2b in monocytes", "of adora2b in monocytes correlates", "adora2b in monocytes correlates with", "in monocytes correlates with higher", "monocytes correlates with higher leishmania", "correlates with higher leishmania donovani", "with higher leishmania donovani parasites", "higher leishmania donovani parasites loads", "leishmania donovani parasites loads alongside", "donovani parasites loads alongside increment", "parasites loads alongside increment of", "loads alongside increment of il10", "alongside increment of il10 production", "of il10 production vijayamahantesh", "il10 production vijayamahantesh et", "production vijayamahantesh et al.", "vijayamahantesh et al. 2016 .", "et al. 2016 . exacerbation", "al. 2016 . exacerbation of", "2016 . exacerbation of lesion", ". exacerbation of lesion development", "exacerbation of lesion development in", "of lesion development in l.", "lesion development in l. amazonensis", "development in l. amazonensis infected", "in l. amazonensis infected mice", "l. amazonensis infected mice also", "amazonensis infected mice also correlated", "infected mice also correlated with", "mice also correlated with high", "also correlated with high amounts", "correlated with high amounts of", "with high amounts of ade", "high amounts of ade rib", "of ade rib figueiredo", "ade rib figueiredo et", "rib figueiredo et al." ] }, { "record_id": "GLY_000594_1_2002", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9660826", "r hsa", "hsa 9660826", "r hsa 9660826" ] }, { "record_id": "GLY_000594_1_2002", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "purinergic signaling", "signaling in", "in leishmaniasis", "leishmaniasis infection", "purinergic signaling in", "signaling in leishmaniasis", "in leishmaniasis infection", "purinergic signaling in leishmaniasis", "signaling in leishmaniasis infection", "purinergic signaling in leishmaniasis infection", "the purinoreceptors", "purinoreceptors are", "are divided", "divided into", "into inotropic", "and metabotropic", "subtypes whose", "whose ligands", "ligands are", "are the", "the nucleotides", "nucleotides atp", "atp and", "and udp", "udp respectively", "cekic et", "et al.", "al. 2016", "2016 .", ". the", "the binding", "binding of", "of these", "these nucleotides", "nucleotides to", "to their", "their receptors", "receptors on", "on macrophages", "macrophages have", "have been", "been associated", "associated with", "with the", "the activation", "activation of", "of the", "the inflammasome", "inflammasome leading", "leading to", "to the", "the subsequent", "subsequent activation", "of interleukin", "interleukin 1", "1 beta", "and tnf", "tnf \u03b1", "2016 &", "& figueiredo", "figueiredo et", "the liberation", "liberation of", "of atp", "atp comes", "comes from", "from tissues", "tissues facing", "facing stressful", "stressful stimuli", "stimuli such", "such as", "as a", "a tissue", "tissue injury", "injury or", "or microorganism", "microorganism infection", "amongst others.", "others. as", "a regulatory", "regulatory mechanism", "certain enzymes", "enzymes can", "can reduce", "reduce atp", "atp to", "to adenosine", "adenosine and", "and a", "a nucleoside", "nucleoside can", "can stimulate", "stimulate signalling", "signalling pathways", "pathways leading", "the synthesis", "synthesis of", "of anti", "anti inflammatory", "inflammatory cytokines", ".
              ", "

              the", "
              the activation", "the receptor", "receptor p2rx7", "p2rx7 was", "was shown", "shown to", "to lead", "lead to", "of killing", "killing mechanisms", "mechanisms or", "or cell", "cell death", "death programs", "ending up", "up in", "in the", "the elimination", "elimination of", "of microbes", "microbes such", "as leishmania", "leishmania amazonensis", "mycobacterium tuberculosis", "chlamydia psittaci", "and toxoplasma", "toxoplasma gondii", "coutinho silva", "silva et", "al. 2012", "2012 &", "& idzko", "2014 .", "the purinoreceptors are", "purinoreceptors are divided", "are divided into", "divided into inotropic", "inotropic p2xr", "p2xr and", "metabotropic p2yr", "p2yr subtypes", "subtypes whose ligands", "whose ligands are", "ligands are the", "are the nucleotides", "the nucleotides atp", "nucleotides atp and", "atp and udp", "and udp respectively", "respectively cekic", "cekic et al.", "et al. 2016", "al. 2016 .", "2016 . the", ". the binding", "the binding of", "binding of these", "of these nucleotides", "these nucleotides to", "nucleotides to their", "to their receptors", "their receptors on", "receptors on macrophages", "on macrophages have", "macrophages have been", "have been associated", "been associated with", "associated with the", "with the activation", "the activation of", "activation of the", "of the inflammasome", "the inflammasome leading", "inflammasome leading to", "leading to the", "to the subsequent", "the subsequent activation", "subsequent activation of", "activation of interleukin", "of interleukin 1", "interleukin 1 beta", "beta il1\u03b2", "il1\u03b2 and", "and tnf \u03b1", "\u03b1 cekic", "al. 2016 &", "2016 & figueiredo", "& figueiredo et", "figueiredo et al.", ". the liberation", "the liberation of", "liberation of atp", "of atp comes", "atp comes from", "comes from tissues", "from tissues facing", "tissues facing stressful", "facing stressful stimuli", "stressful stimuli such", "stimuli such as", "such as a", "as a tissue", "a tissue injury", "tissue injury or", "injury or microorganism", "or microorganism infection", "infection amongst", "amongst others. as", "others. as a", "as a regulatory", "a regulatory mechanism", "mechanism certain", "certain enzymes can", "enzymes can reduce", "can reduce atp", "reduce atp to", "atp to adenosine", "to adenosine and", "adenosine and a", "and a nucleoside", "a nucleoside can", "nucleoside can stimulate", "can stimulate signalling", "stimulate signalling pathways", "signalling pathways leading", "pathways leading to", "to the synthesis", "the synthesis of", "synthesis of anti", "of anti inflammatory", "anti inflammatory cytokines", "cytokines cekic", "2016 .
              ", ".

              the", "

              the activation", "
              the activation of", "of the receptor", "the receptor p2rx7", "receptor p2rx7 was", "p2rx7 was shown", "was shown to", "shown to lead", "to lead to", "lead to the", "to the activation", "activation of killing", "of killing mechanisms", "killing mechanisms or", "mechanisms or cell", "or cell death", "cell death programs", "programs ending", "ending up in", "up in the", "in the elimination", "the elimination of", "elimination of microbes", "of microbes such", "microbes such as", "such as leishmania", "as leishmania amazonensis", "amazonensis mycobacterium", "tuberculosis chlamydia", "psittaci and", "and toxoplasma gondii", "gondii coutinho", "coutinho silva et", "silva et al.", "et al. 2012", "al. 2012 &", "2012 & idzko", "idzko 2014", "the purinoreceptors are divided", "purinoreceptors are divided into", "are divided into inotropic", "into inotropic p2xr", "p2xr and metabotropic", "and metabotropic p2yr", "p2yr subtypes whose", "subtypes whose ligands are", "whose ligands are the", "ligands are the nucleotides", "are the nucleotides atp", "the nucleotides atp and", "nucleotides atp and udp", "atp and udp respectively", "udp respectively cekic", "respectively cekic et", "cekic et al. 2016", "et al. 2016 .", "al. 2016 . the", "2016 . the binding", ". the binding of", "the binding of these", "binding of these nucleotides", "of these nucleotides to", "these nucleotides to their", "nucleotides to their receptors", "to their receptors on", "their receptors on macrophages", "receptors on macrophages have", "on macrophages have been", "macrophages have been associated", "have been associated with", "been associated with the", "associated with the activation", "with the activation of", "the activation of the", "activation of the inflammasome", "of the inflammasome leading", "the inflammasome leading to", "inflammasome leading to the", "leading to the subsequent", "to the subsequent activation", "the subsequent activation of", "subsequent activation of interleukin", "activation of interleukin 1", "of interleukin 1 beta", "1 beta il1\u03b2", "il1\u03b2 and tnf", "tnf \u03b1 cekic", "\u03b1 cekic et", "et al. 2016 &", "al. 2016 & figueiredo", "2016 & figueiredo et", "& figueiredo et al.", "figueiredo et al. 2016", "2016 . the liberation", ". the liberation of", "the liberation of atp", "liberation of atp comes", "of atp comes from", "atp comes from tissues", "comes from tissues facing", "from tissues facing stressful", "tissues facing stressful stimuli", "facing stressful stimuli such", "stressful stimuli such as", "stimuli such as a", "such as a tissue", "as a tissue injury", "a tissue injury or", "tissue injury or microorganism", "injury or microorganism infection", "microorganism infection amongst", "infection amongst others.", "amongst others. as a", "others. as a regulatory", "as a regulatory mechanism", "regulatory mechanism certain", "mechanism certain enzymes", "certain enzymes can reduce", "enzymes can reduce atp", "can reduce atp to", "reduce atp to adenosine", "atp to adenosine and", "to adenosine and a", "adenosine and a nucleoside", "and a nucleoside can", "a nucleoside can stimulate", "nucleoside can stimulate signalling", "can stimulate signalling pathways", "stimulate signalling pathways leading", "signalling pathways leading to", "pathways leading to the", "leading to the synthesis", "to the synthesis of", "the synthesis of anti", "synthesis of anti inflammatory", "of anti inflammatory cytokines", "inflammatory cytokines cekic", "cytokines cekic et", "al. 2016 .
              ", "2016 .

              the", ".

              the activation", "

              the activation of", "
              the activation of the", "activation of the receptor", "of the receptor p2rx7", "the receptor p2rx7 was", "receptor p2rx7 was shown", "p2rx7 was shown to", "was shown to lead", "shown to lead to", "to lead to the", "lead to the activation", "to the activation of", "the activation of killing", "activation of killing mechanisms", "of killing mechanisms or", "killing mechanisms or cell", "mechanisms or cell death", "or cell death programs", "death programs ending", "programs ending up", "ending up in the", "up in the elimination", "in the elimination of", "the elimination of microbes", "elimination of microbes such", "of microbes such as", "microbes such as leishmania", "such as leishmania amazonensis", "leishmania amazonensis mycobacterium", "amazonensis mycobacterium tuberculosis", "mycobacterium tuberculosis chlamydia", "tuberculosis chlamydia psittaci", "chlamydia psittaci and", "psittaci and toxoplasma", "toxoplasma gondii coutinho", "gondii coutinho silva", "coutinho silva et al.", "silva et al. 2012", "et al. 2012 &", "al. 2012 & idzko", "& idzko 2014", "idzko 2014 .", "the purinoreceptors are divided into", "purinoreceptors are divided into inotropic", "divided into inotropic p2xr", "inotropic p2xr and", "metabotropic p2yr subtypes", "p2yr subtypes whose ligands", "subtypes whose ligands are the", "whose ligands are the nucleotides", "ligands are the nucleotides atp", "are the nucleotides atp and", "the nucleotides atp and udp", "nucleotides atp and udp respectively", "and udp respectively cekic", "udp respectively cekic et", "respectively cekic et al.", "cekic et al. 2016 .", "et al. 2016 . the", "al. 2016 . the binding", "2016 . the binding of", ". the binding of these", "the binding of these nucleotides", "binding of these nucleotides to", "of these nucleotides to their", "these nucleotides to their receptors", "nucleotides to their receptors on", "to their receptors on macrophages", "their receptors on macrophages have", "receptors on macrophages have been", "on macrophages have been associated", "macrophages have been associated with", "have been associated with the", "been associated with the activation", "associated with the activation of", "with the activation of the", "the activation of the inflammasome", "activation of the inflammasome leading", "of the inflammasome leading to", "the inflammasome leading to the", "inflammasome leading to the subsequent", "leading to the subsequent activation", "to the subsequent activation of", "the subsequent activation of interleukin", "subsequent activation of interleukin 1", "activation of interleukin 1 beta", "interleukin 1 beta il1\u03b2", "beta il1\u03b2 and", "il1\u03b2 and tnf \u03b1", "and tnf \u03b1 cekic", "tnf \u03b1 cekic et", "\u03b1 cekic et al.", "cekic et al. 2016 &", "et al. 2016 & figueiredo", "al. 2016 & figueiredo et", "2016 & figueiredo et al.", "& figueiredo et al. 2016", "figueiredo et al. 2016 .", "al. 2016 . the liberation", "2016 . the liberation of", ". the liberation of atp", "the liberation of atp comes", "liberation of atp comes from", "of atp comes from tissues", "atp comes from tissues facing", "comes from tissues facing stressful", "from tissues facing stressful stimuli", "tissues facing stressful stimuli such", "facing stressful stimuli such as", "stressful stimuli such as a", "stimuli such as a tissue", "such as a tissue injury", "as a tissue injury or", "a tissue injury or microorganism", "tissue injury or microorganism infection", "or microorganism infection amongst", "microorganism infection amongst others.", "infection amongst others. as", "amongst others. as a regulatory", "others. as a regulatory mechanism", "a regulatory mechanism certain", "regulatory mechanism certain enzymes", "mechanism certain enzymes can", "certain enzymes can reduce atp", "enzymes can reduce atp to", "can reduce atp to adenosine", "reduce atp to adenosine and", "atp to adenosine and a", "to adenosine and a nucleoside", "adenosine and a nucleoside can", "and a nucleoside can stimulate", "a nucleoside can stimulate signalling", "nucleoside can stimulate signalling pathways", "can stimulate signalling pathways leading", "stimulate signalling pathways leading to", "signalling pathways leading to the", "pathways leading to the synthesis", "leading to the synthesis of", "to the synthesis of anti", "the synthesis of anti inflammatory", "synthesis of anti inflammatory cytokines", "anti inflammatory cytokines cekic", "inflammatory cytokines cekic et", "cytokines cekic et al.", "et al. 2016 .
              ", "al. 2016 .

              the", "2016 .

              the activation", ".

              the activation of", "

              the activation of the", "
              the activation of the receptor", "activation of the receptor p2rx7", "of the receptor p2rx7 was", "the receptor p2rx7 was shown", "receptor p2rx7 was shown to", "p2rx7 was shown to lead", "was shown to lead to", "shown to lead to the", "to lead to the activation", "lead to the activation of", "to the activation of killing", "the activation of killing mechanisms", "activation of killing mechanisms or", "of killing mechanisms or cell", "killing mechanisms or cell death", "mechanisms or cell death programs", "cell death programs ending", "death programs ending up", "programs ending up in", "ending up in the elimination", "up in the elimination of", "in the elimination of microbes", "the elimination of microbes such", "elimination of microbes such as", "of microbes such as leishmania", "microbes such as leishmania amazonensis", "as leishmania amazonensis mycobacterium", "leishmania amazonensis mycobacterium tuberculosis", "mycobacterium tuberculosis chlamydia psittaci", "chlamydia psittaci and toxoplasma", "psittaci and toxoplasma gondii", "and toxoplasma gondii coutinho", "toxoplasma gondii coutinho silva", "gondii coutinho silva et", "coutinho silva et al. 2012", "silva et al. 2012 &", "et al. 2012 & idzko", "2012 & idzko 2014", "& idzko 2014 ." ] }, { "record_id": "GLY_000594_1_2003", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9661069", "r hsa", "hsa 9661069", "r hsa 9661069" ] }, { "record_id": "GLY_000594_1_2003", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective binding", "binding of", "of rb1", "rb1 mutants", "mutants to", "to e2f1", "defective binding of", "binding of rb1", "of rb1 mutants", "rb1 mutants to", "mutants to e2f1", "e2f1 e2f2", "e2f2 e2f3", "defective binding of rb1", "binding of rb1 mutants", "of rb1 mutants to", "rb1 mutants to e2f1", "to e2f1 e2f2", "defective binding of rb1 mutants", "binding of rb1 mutants to", "of rb1 mutants to e2f1", "mutants to e2f1 e2f2", "e2f1 e2f2 e2f3", "this pathway", "pathway describes", "describes impaired", "impaired binding", "rb1 pocket", "pocket domain", "domain mutants", "to activating", "activating e2fs", "e2f2 and", "and e2f3", "templeton et", "et al.", "al. 1991", "helin et", "al. 1993", "otterson et", "al. 1997", "ji et", "al. 2004", "2004 .", "this pathway describes", "pathway describes impaired", "describes impaired binding", "impaired binding of", "of rb1 pocket", "rb1 pocket domain", "pocket domain mutants", "domain mutants to", "mutants to activating", "to activating e2fs", "e2fs e2f1", "e2f2 and e2f3", "e2f3 templeton", "templeton et al.", "et al. 1991", "1991 helin", "helin et al.", "et al. 1993", "1993 otterson", "otterson et al.", "et al. 1997", "1997 ji", "ji et al.", "et al. 2004", "al. 2004 .", "this pathway describes impaired", "pathway describes impaired binding", "describes impaired binding of", "impaired binding of rb1", "binding of rb1 pocket", "of rb1 pocket domain", "rb1 pocket domain mutants", "pocket domain mutants to", "domain mutants to activating", "mutants to activating e2fs", "activating e2fs e2f1", "e2f1 e2f2 and", "and e2f3 templeton", "e2f3 templeton et", "templeton et al. 1991", "al. 1991 helin", "1991 helin et", "helin et al. 1993", "al. 1993 otterson", "1993 otterson et", "otterson et al. 1997", "al. 1997 ji", "1997 ji et", "ji et al. 2004", "et al. 2004 .", "this pathway describes impaired binding", "pathway describes impaired binding of", "describes impaired binding of rb1", "impaired binding of rb1 pocket", "binding of rb1 pocket domain", "of rb1 pocket domain mutants", "rb1 pocket domain mutants to", "pocket domain mutants to activating", "domain mutants to activating e2fs", "to activating e2fs e2f1", "e2fs e2f1 e2f2", "e2f1 e2f2 and e2f3", "e2f2 and e2f3 templeton", "and e2f3 templeton et", "e2f3 templeton et al.", "et al. 1991 helin", "al. 1991 helin et", "1991 helin et al.", "et al. 1993 otterson", "al. 1993 otterson et", "1993 otterson et al.", "et al. 1997 ji", "al. 1997 ji et", "1997 ji et al.", "ji et al. 2004 ." ] }, { "record_id": "GLY_000594_1_2004", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9665686", "r hsa", "hsa 9665686", "r hsa 9665686" ] }, { "record_id": "GLY_000594_1_2004", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by erbb2", "erbb2 tmd/jmd", "tmd/jmd mutants", "signaling by erbb2", "by erbb2 tmd/jmd", "erbb2 tmd/jmd mutants", "signaling by erbb2 tmd/jmd", "by erbb2 tmd/jmd mutants", "signaling by erbb2 tmd/jmd mutants", "recurrent missense", "missense mutations", "mutations in", "in regions", "regions encoding", "encoding the", "the transmembrane", "transmembrane domain", "and the", "the juxtamembrane", "juxtamembrane domain", "are frequently", "frequently reported", "reported in", "in cancer.", "cancer. the", "the erbb2", "erbb2 tmd", "tmd mutants", "mutants include", "include erbb2", "erbb2 v659e", "erbb2 v659k", "erbb2 g660d", "erbb2 g660r", "erbb2 s653c", "erbb2 r677l", "r677l and", "and erbb2", "erbb2 r678q.", "r678q. the", "erbb2 jmd", "jmd mutants", "erbb2 e693k", "e693k and", "erbb2 q709l.", "q709l. erbb2", "g660d and", "and s653c", "de martino", "martino et", "et al.", "al. 2014", "are known", "known to", "to be", "be activating.", "activating. erbb2", "mutants erbb2", "erbb2 r678q", "erbb2 q709l", "q709l mutations", "mutations may", "may be", "be activating", "activating when", "when co", "co expressed", "expressed with", "with a", "a wild", "wild type", "type erbb2", "erbb2 receptor", "pahuja et", "al. 2018", "2018 .", ". tmd", "tmd and", "and jmd", "jmd mutations", "mutations can", "can activate", "activate erbb2", "erbb2 signaling", "by improving", "improving the", "the active", "active dimer", "dimer interface", "interface or", "or by", "by stabilizing", "stabilizing the", "active conformation.", "conformation. tmd/jmd", "mutants that", "that are", "are activating", "activating in", "in the", "the presence", "presence of", "of wild", "such as", "as erbb2", "may form", "form homodimers", "homodimers with", "with the", "the wild", "2018 .

              based", ".

              based on", "on trans", "trans autophosphorylation", "autophosphorylation of", "of erbb2", "erbb2 and", "and its", "its dimerization", "dimerization partners", "partners egfr", "egfr and", "and erbb3", "the following", "following erbb2", "mutants are", "are assumed", "assumed to", "to form", "form heterodimers", "heterodimers with", "with egfr", "and erbb3:
              erbb2", "erbb3:
              erbb2 s653c", "2014
              erbb2", "
              erbb2 r678q", "bose et", "al. 2013", "2018 .

              phosphorylation", ".

              phosphorylation of", "of tyrosine", "tyrosine residues", "residues in", "the c", "c tail", "tail of", "erbb2 was", "was shown", "shown for", "for the", "tmd/jmd mutants:
              erbb2", "mutants:
              erbb2 v659e", "
              erbb2 v659k", "
              erbb2 g660d", "
              erbb2 g660r", "
              erbb2 s653c", "phosphorylation at", "at y1248", "y1248 demonstrated", "
              erbb2 r677l", "2018

              phosphorylation", "

              phosphorylation of", "of egfr", "egfr was", "was demonstrated", "demonstrated for", "for erbb2", "at y1068", "y1068 .

              phosphorylation", "of erbb3", "erbb3 was", "at y1197", "y1197 .

              activation", ".

              activation of", "of downstream", "downstream ras", "ras signaling", "signaling was", "through activating", "activating tyrosine", "tyrosine phosphorylation", "phosphorylation on", "on erks", "mapk1 and", "and mapk3", "and shc1.

              activation", "shc1.

              activation of", "downstream plcg1", "plcg1 signaling", "on plcg1", "2013 .

              activation", "of pi3k/akt", "pi3k/akt signaling", "mutants has", "has not", "not been", "been tested.

              signaling", "tested.

              signaling by", "q709l has", "been sufficiently", "sufficiently studied", "studied and", "and they", "they are", "are annotated", "annotated as", "as candidates.

              the", "candidates.

              the following", "are sensitive", "sensitive to", "the therapeutic", "therapeutic antibody", "antibody trastuzumab", "herceptin :
              erbb2", ":
              erbb2 v659e", "
              erbb2 q709l", "

              with respect", "respect to", "to pertuzumab", "a therapeutic", "antibody that", "that block", "block ligand", "ligand driven", "driven heterodimerization", "heterodimerization of", "r678q is", "is sensitive", "while erbb2", "g660r and", "and probably", "probably erbb2", "q709l are", "are resistant", "2018 .

              the", ".

              the following", "to lapatinib:
              erbb2", "lapatinib:
              erbb2 s653c", "

              the following", "to neratinib:
              erbb2", "neratinib:
              erbb2 v659e", "to afatinib:
              erbb2", "afatinib:
              erbb2 g660d", "recurrent missense mutations", "missense mutations in", "mutations in regions", "in regions encoding", "regions encoding the", "encoding the transmembrane", "the transmembrane domain", "domain tmd", "and the juxtamembrane", "the juxtamembrane domain", "domain jmd", "jmd are", "are frequently reported", "frequently reported in", "reported in cancer.", "in cancer. the", "cancer. the erbb2", "the erbb2 tmd", "erbb2 tmd mutants", "tmd mutants include", "mutants include erbb2", "include erbb2 v659e", "v659e erbb2", "v659k erbb2", "g660d erbb2", "g660r erbb2", "s653c erbb2", "erbb2 r677l and", "r677l and erbb2", "and erbb2 r678q.", "erbb2 r678q. the", "r678q. the erbb2", "the erbb2 jmd", "erbb2 jmd mutants", "jmd mutants include", "include erbb2 e693k", "erbb2 e693k and", "e693k and erbb2", "and erbb2 q709l.", "erbb2 q709l. erbb2", "q709l. erbb2 tmd", "erbb2 g660d and", "g660d and s653c", "s653c de", "de martino et", "martino et al.", "et al. 2014", "2014 are", "are known to", "known to be", "to be activating.", "be activating. erbb2", "activating. erbb2 tmd/jmd", "tmd/jmd mutants erbb2", "mutants erbb2 r678q", "r678q erbb2", "and erbb2 q709l", "erbb2 q709l mutations", "q709l mutations may", "mutations may be", "may be activating", "be activating when", "activating when co", "when co expressed", "co expressed with", "expressed with a", "with a wild", "a wild type", "wild type erbb2", "type erbb2 receptor", "receptor pahuja", "pahuja et al.", "et al. 2018", "al. 2018 .", "2018 . tmd", ". tmd and", "tmd and jmd", "and jmd mutations", "jmd mutations can", "mutations can activate", "can activate erbb2", "activate erbb2 signaling", "erbb2 signaling by", "signaling by improving", "by improving the", "improving the active", "the active dimer", "active dimer interface", "dimer interface or", "interface or by", "or by stabilizing", "by stabilizing the", "stabilizing the active", "the active conformation.", "active conformation. tmd/jmd", "conformation. tmd/jmd mutants", "tmd/jmd mutants that", "mutants that are", "that are activating", "are activating in", "activating in the", "in the presence", "the presence of", "presence of wild", "of wild type", "erbb2 such", "such as erbb2", "as erbb2 r678q", "r678q may", "may form homodimers", "form homodimers with", "homodimers with the", "with the wild", "the wild type", "erbb2 pahuja", "al. 2018 .

              based", "2018 .

              based on", ".

              based on trans", "on trans autophosphorylation", "trans autophosphorylation of", "autophosphorylation of erbb2", "of erbb2 and", "erbb2 and its", "and its dimerization", "its dimerization partners", "dimerization partners egfr", "partners egfr and", "egfr and erbb3", "erbb3 the", "the following erbb2", "following erbb2 tmd/jmd", "tmd/jmd mutants are", "mutants are assumed", "are assumed to", "assumed to form", "to form heterodimers", "form heterodimers with", "heterodimers with egfr", "with egfr and", "egfr and erbb3:
              erbb2", "and erbb3:
              erbb2 s653c", "al. 2014
              erbb2", "2014
              erbb2 r678q", "r678q bose", "bose et al.", "et al. 2013", "2013 pahuja", "al. 2018 .

              phosphorylation", "2018 .

              phosphorylation of", ".

              phosphorylation of tyrosine", "of tyrosine residues", "tyrosine residues in", "residues in the", "in the c", "the c tail", "c tail of", "tail of erbb2", "of erbb2 was", "erbb2 was shown", "was shown for", "shown for the", "for the following", "erbb2 tmd/jmd mutants:
              erbb2", "tmd/jmd mutants:
              erbb2 v659e", "v659e pahuja", "2018
              erbb2", "v659k pahuja", "g660d pahuja", "g660r pahuja", "phosphorylation at y1248", "at y1248 demonstrated", "demonstrated
              erbb2", "r677l pahuja", "2013 de", "demonstrated pahuja", "q709l pahuja", "al. 2018

              phosphorylation", "2018

              phosphorylation of", "

              phosphorylation of tyrosine", "tail of egfr", "of egfr was", "egfr was demonstrated", "was demonstrated for", "demonstrated for erbb2", "for erbb2 s653c", "phosphorylation at y1068", "y1068 and", "and erbb2 r678q", "at y1068 .

              phosphorylation", "y1068 .

              phosphorylation of", "tail of erbb3", "of erbb3 was", "erbb3 was demonstrated", "phosphorylation at y1197", "y1197 and", "at y1197 .

              activation", "y1197 .

              activation of", ".

              activation of downstream", "of downstream ras", "downstream ras signaling", "ras signaling was", "signaling was shown", "shown for erbb2", "2014 and", "2014 through", "through activating tyrosine", "activating tyrosine phosphorylation", "tyrosine phosphorylation on", "phosphorylation on erks", "erks mapk1", "mapk1 and mapk3", "mapk3 and", "and shc1.

              activation of", "shc1.

              activation of downstream", "of downstream plcg1", "downstream plcg1 signaling", "plcg1 signaling was", "signaling was demonstrated", "for erbb2 r678q", "r678q through", "phosphorylation on plcg1", "plcg1 bose", "al. 2013 .

              activation", "2013 .

              activation of", ".

              activation of pi3k/akt", "of pi3k/akt signaling", "pi3k/akt signaling by", "tmd/jmd mutants has", "mutants has not", "has not been", "not been tested.

              signaling", "been tested.

              signaling by", "tested.

              signaling by erbb2", "by erbb2 v659k", "r677l erbb2", "erbb2 q709l has", "q709l has not", "not been sufficiently", "been sufficiently studied", "sufficiently studied and", "studied and they", "and they are", "they are annotated", "are annotated as", "annotated as candidates.

              the", "as candidates.

              the following", "candidates.

              the following erbb2", "mutants are sensitive", "are sensitive to", "to the", "the therapeutic antibody", "therapeutic antibody trastuzumab", "trastuzumab herceptin", "herceptin :
              erbb2 v659e", "2018

              with", "

              with respect to", "respect to pertuzumab", "pertuzumab a", "a therapeutic antibody", "therapeutic antibody that", "antibody that block", "that block ligand", "block ligand driven", "ligand driven heterodimerization", "driven heterodimerization of", "heterodimerization of erbb2", "erbb2 erbb2", "erbb2 r678q is", "r678q is sensitive", "is sensitive to", "sensitive to pertuzumab", "pertuzumab while", "while erbb2 v659e", "erbb2 g660r and", "g660r and probably", "and probably erbb2", "probably erbb2 q709l", "erbb2 q709l are", "q709l are resistant", "resistant pahuja", "al. 2018 .

              the", "2018 .

              the following", ".

              the following erbb2", "sensitive to lapatinib:
              erbb2", "to lapatinib:
              erbb2 s653c", "2013

              the", "

              the following erbb2", "sensitive to neratinib:
              erbb2", "to neratinib:
              erbb2 v659e", "2018

              the", "sensitive to afatinib:
              erbb2", "to afatinib:
              erbb2 g660d", "r678q pahuja", "recurrent missense mutations in", "missense mutations in regions", "mutations in regions encoding", "in regions encoding the", "regions encoding the transmembrane", "encoding the transmembrane domain", "transmembrane domain tmd", "tmd and the", "and the juxtamembrane domain", "juxtamembrane domain jmd", "jmd are frequently", "are frequently reported in", "frequently reported in cancer.", "reported in cancer. the", "in cancer. the erbb2", "cancer. the erbb2 tmd", "the erbb2 tmd mutants", "erbb2 tmd mutants include", "tmd mutants include erbb2", "mutants include erbb2 v659e", "erbb2 v659e erbb2", "v659e erbb2 v659k", "erbb2 v659k erbb2", "v659k erbb2 g660d", "erbb2 g660d erbb2", "g660d erbb2 g660r", "erbb2 g660r erbb2", "g660r erbb2 s653c", "erbb2 s653c erbb2", "s653c erbb2 r677l", "erbb2 r677l and erbb2", "r677l and erbb2 r678q.", "and erbb2 r678q. the", "erbb2 r678q. the erbb2", "r678q. the erbb2 jmd", "the erbb2 jmd mutants", "erbb2 jmd mutants include", "jmd mutants include erbb2", "mutants include erbb2 e693k", "include erbb2 e693k and", "erbb2 e693k and erbb2", "e693k and erbb2 q709l.", "and erbb2 q709l. erbb2", "erbb2 q709l. erbb2 tmd", "q709l. erbb2 tmd mutants", "tmd mutants erbb2", "mutants erbb2 v659e", "v659e erbb2 g660d", "erbb2 g660d and s653c", "and s653c de", "s653c de martino", "de martino et al.", "martino et al. 2014", "al. 2014 are", "2014 are known", "are known to be", "known to be activating.", "to be activating. erbb2", "be activating. erbb2 tmd/jmd", "activating. erbb2 tmd/jmd mutants", "erbb2 tmd/jmd mutants erbb2", "tmd/jmd mutants erbb2 r678q", "erbb2 r678q erbb2", "r678q erbb2 e693k", "and erbb2 q709l mutations", "erbb2 q709l mutations may", "q709l mutations may be", "mutations may be activating", "may be activating when", "be activating when co", "activating when co expressed", "when co expressed with", "co expressed with a", "expressed with a wild", "with a wild type", "a wild type erbb2", "wild type erbb2 receptor", "erbb2 receptor pahuja", "receptor pahuja et", "pahuja et al. 2018", "et al. 2018 .", "al. 2018 . tmd", "2018 . tmd and", ". tmd and jmd", "tmd and jmd mutations", "and jmd mutations can", "jmd mutations can activate", "mutations can activate erbb2", "can activate erbb2 signaling", "activate erbb2 signaling by", "erbb2 signaling by improving", "signaling by improving the", "by improving the active", "improving the active dimer", "the active dimer interface", "active dimer interface or", "dimer interface or by", "interface or by stabilizing", "or by stabilizing the", "by stabilizing the active", "stabilizing the active conformation.", "the active conformation. tmd/jmd", "active conformation. tmd/jmd mutants", "conformation. tmd/jmd mutants that", "tmd/jmd mutants that are", "mutants that are activating", "that are activating in", "are activating in the", "activating in the presence", "in the presence of", "the presence of wild", "presence of wild type", "of wild type erbb2", "type erbb2 such", "erbb2 such as", "such as erbb2 r678q", "erbb2 r678q may", "r678q may form", "may form homodimers with", "form homodimers with the", "homodimers with the wild", "with the wild type", "the wild type erbb2", "type erbb2 pahuja", "erbb2 pahuja et", "et al. 2018 .

              based", "al. 2018 .

              based on", "2018 .

              based on trans", ".

              based on trans autophosphorylation", "on trans autophosphorylation of", "trans autophosphorylation of erbb2", "autophosphorylation of erbb2 and", "of erbb2 and its", "erbb2 and its dimerization", "and its dimerization partners", "its dimerization partners egfr", "dimerization partners egfr and", "partners egfr and erbb3", "and erbb3 the", "erbb3 the following", "the following erbb2 tmd/jmd", "following erbb2 tmd/jmd mutants", "erbb2 tmd/jmd mutants are", "tmd/jmd mutants are assumed", "mutants are assumed to", "are assumed to form", "assumed to form heterodimers", "to form heterodimers with", "form heterodimers with egfr", "heterodimers with egfr and", "with egfr and erbb3:
              erbb2", "egfr and erbb3:
              erbb2 s653c", "erbb3:
              erbb2 s653c de", "et al. 2014
              erbb2", "al. 2014
              erbb2 r678q", "
              erbb2 r678q bose", "r678q bose et", "bose et al. 2013", "al. 2013 pahuja", "2013 pahuja et", "et al. 2018 .

              phosphorylation", "al. 2018 .

              phosphorylation of", "2018 .

              phosphorylation of tyrosine", ".

              phosphorylation of tyrosine residues", "of tyrosine residues in", "tyrosine residues in the", "residues in the c", "in the c tail", "the c tail of", "c tail of erbb2", "tail of erbb2 was", "of erbb2 was shown", "erbb2 was shown for", "was shown for the", "shown for the following", "for the following erbb2", "following erbb2 tmd/jmd mutants:
              erbb2", "erbb2 tmd/jmd mutants:
              erbb2 v659e", "mutants:
              erbb2 v659e pahuja", "v659e pahuja et", "al. 2018
              erbb2", "2018
              erbb2 v659k", "
              erbb2 v659k pahuja", "v659k pahuja et", "2018
              erbb2 g660d", "
              erbb2 g660d pahuja", "g660d pahuja et", "2018
              erbb2 g660r", "
              erbb2 g660r pahuja", "g660r pahuja et", "2018
              erbb2 s653c", "
              erbb2 s653c de", "2014 phosphorylation", "phosphorylation at y1248 demonstrated", "y1248 demonstrated
              erbb2", "demonstrated
              erbb2 r677l", "
              erbb2 r677l pahuja", "r677l pahuja et", "2018
              erbb2 r678q", "al. 2013 de", "2013 de martino", "y1248 demonstrated pahuja", "demonstrated pahuja et", "2018 erbb2", "erbb2 q709l pahuja", "q709l pahuja et", "et al. 2018

              phosphorylation", "al. 2018

              phosphorylation of", "2018

              phosphorylation of tyrosine", "

              phosphorylation of tyrosine residues", "c tail of egfr", "tail of egfr was", "of egfr was demonstrated", "egfr was demonstrated for", "was demonstrated for erbb2", "demonstrated for erbb2 s653c", "erbb2 s653c de", "at y1068 and", "y1068 and erbb2", "erbb2 r678q bose", "phosphorylation at y1068 .

              phosphorylation", "at y1068 .

              phosphorylation of", "y1068 .

              phosphorylation of tyrosine", "c tail of erbb3", "tail of erbb3 was", "of erbb3 was demonstrated", "erbb3 was demonstrated for", "at y1197 and", "y1197 and erbb2", "phosphorylation at y1197 .

              activation", "at y1197 .

              activation of", "y1197 .

              activation of downstream", ".

              activation of downstream ras", "of downstream ras signaling", "downstream ras signaling was", "ras signaling was shown", "signaling was shown for", "was shown for erbb2", "shown for erbb2 s653c", "al. 2014 and", "2014 and erbb2", "al. 2014 through", "2014 through activating", "through activating tyrosine phosphorylation", "activating tyrosine phosphorylation on", "tyrosine phosphorylation on erks", "on erks mapk1", "erks mapk1 and", "and mapk3 and", "mapk3 and shc1.

              activation", "and shc1.

              activation of downstream", "shc1.

              activation of downstream plcg1", "of downstream plcg1 signaling", "downstream plcg1 signaling was", "plcg1 signaling was demonstrated", "signaling was demonstrated for", "demonstrated for erbb2 r678q", "erbb2 r678q through", "r678q through activating", "tyrosine phosphorylation on plcg1", "on plcg1 bose", "plcg1 bose et", "et al. 2013 .

              activation", "al. 2013 .

              activation of", "2013 .

              activation of pi3k/akt", ".

              activation of pi3k/akt signaling", "of pi3k/akt signaling by", "pi3k/akt signaling by erbb2", "erbb2 tmd/jmd mutants has", "tmd/jmd mutants has not", "mutants has not been", "has not been tested.

              signaling", "not been tested.

              signaling by", "been tested.

              signaling by erbb2", "tested.

              signaling by erbb2 v659k", "g660r erbb2 r677l", "erbb2 r677l erbb2", "r677l erbb2 e693k", "e693k and erbb2 q709l", "and erbb2 q709l has", "erbb2 q709l has not", "q709l has not been", "has not been sufficiently", "not been sufficiently studied", "been sufficiently studied and", "sufficiently studied and they", "studied and they are", "and they are annotated", "they are annotated as", "are annotated as candidates.

              the", "annotated as candidates.

              the following", "as candidates.

              the following erbb2", "candidates.

              the following erbb2 tmd/jmd", "tmd/jmd mutants are sensitive", "mutants are sensitive to", "sensitive to the", "to the therapeutic", "the therapeutic antibody trastuzumab", "antibody trastuzumab herceptin", "trastuzumab herceptin :
              erbb2", ":
              erbb2 v659e pahuja", "2018
              erbb2 q709l", "
              erbb2 q709l pahuja", "al. 2018

              with", "2018

              with respect", "

              with respect to pertuzumab", "to pertuzumab a", "pertuzumab a therapeutic", "a therapeutic antibody that", "therapeutic antibody that block", "antibody that block ligand", "that block ligand driven", "block ligand driven heterodimerization", "ligand driven heterodimerization of", "driven heterodimerization of erbb2", "of erbb2 erbb2", "erbb2 erbb2 r678q", "erbb2 r678q is sensitive", "r678q is sensitive to", "is sensitive to pertuzumab", "to pertuzumab while", "pertuzumab while erbb2", "erbb2 g660r and probably", "g660r and probably erbb2", "and probably erbb2 q709l", "probably erbb2 q709l are", "erbb2 q709l are resistant", "are resistant pahuja", "resistant pahuja et", "et al. 2018 .

              the", "al. 2018 .

              the following", "2018 .

              the following erbb2", ".

              the following erbb2 tmd/jmd", "are sensitive to lapatinib:
              erbb2", "sensitive to lapatinib:
              erbb2 s653c", "lapatinib:
              erbb2 s653c de", "al. 2013

              the", "2013

              the following", "

              the following erbb2 tmd/jmd", "are sensitive to neratinib:
              erbb2", "sensitive to neratinib:
              erbb2 v659e", "neratinib:
              erbb2 v659e pahuja", "al. 2018

              the", "2018

              the following", "are sensitive to afatinib:
              erbb2", "sensitive to afatinib:
              erbb2 g660d", "afatinib:
              erbb2 g660d pahuja", "
              erbb2 r678q pahuja", "r678q pahuja et", "recurrent missense mutations in regions", "missense mutations in regions encoding", "mutations in regions encoding the", "in regions encoding the transmembrane", "regions encoding the transmembrane domain", "the transmembrane domain tmd", "domain tmd and", "tmd and the juxtamembrane", "the juxtamembrane domain jmd", "domain jmd are", "jmd are frequently reported", "are frequently reported in cancer.", "frequently reported in cancer. the", "reported in cancer. the erbb2", "in cancer. the erbb2 tmd", "cancer. the erbb2 tmd mutants", "the erbb2 tmd mutants include", "erbb2 tmd mutants include erbb2", "tmd mutants include erbb2 v659e", "include erbb2 v659e erbb2", "erbb2 v659e erbb2 v659k", "erbb2 v659k erbb2 g660d", "erbb2 g660d erbb2 g660r", "erbb2 g660r erbb2 s653c", "erbb2 s653c erbb2 r677l", "s653c erbb2 r677l and", "erbb2 r677l and erbb2 r678q.", "r677l and erbb2 r678q. the", "and erbb2 r678q. the erbb2", "erbb2 r678q. the erbb2 jmd", "r678q. the erbb2 jmd mutants", "the erbb2 jmd mutants include", "erbb2 jmd mutants include erbb2", "jmd mutants include erbb2 e693k", "mutants include erbb2 e693k and", "include erbb2 e693k and erbb2", "erbb2 e693k and erbb2 q709l.", "e693k and erbb2 q709l. erbb2", "and erbb2 q709l. erbb2 tmd", "erbb2 q709l. erbb2 tmd mutants", "erbb2 tmd mutants erbb2", "tmd mutants erbb2 v659e", "erbb2 v659e erbb2 g660d", "v659e erbb2 g660d and", "g660d and s653c de", "and s653c de martino", "s653c de martino et", "de martino et al. 2014", "et al. 2014 are", "al. 2014 are known", "2014 are known to", "are known to be activating.", "known to be activating. erbb2", "to be activating. erbb2 tmd/jmd", "be activating. erbb2 tmd/jmd mutants", "activating. erbb2 tmd/jmd mutants erbb2", "erbb2 tmd/jmd mutants erbb2 r678q", "mutants erbb2 r678q erbb2", "erbb2 r678q erbb2 e693k", "and erbb2 q709l mutations may", "erbb2 q709l mutations may be", "q709l mutations may be activating", "mutations may be activating when", "may be activating when co", "be activating when co expressed", "activating when co expressed with", "when co expressed with a", "co expressed with a wild", "expressed with a wild type", "with a wild type erbb2", "a wild type erbb2 receptor", "type erbb2 receptor pahuja", "erbb2 receptor pahuja et", "receptor pahuja et al.", "pahuja et al. 2018 .", "et al. 2018 . tmd", "al. 2018 . tmd and", "2018 . tmd and jmd", ". tmd and jmd mutations", "tmd and jmd mutations can", "and jmd mutations can activate", "jmd mutations can activate erbb2", "mutations can activate erbb2 signaling", "can activate erbb2 signaling by", "activate erbb2 signaling by improving", "erbb2 signaling by improving the", "signaling by improving the active", "by improving the active dimer", "improving the active dimer interface", "the active dimer interface or", "active dimer interface or by", "dimer interface or by stabilizing", "interface or by stabilizing the", "or by stabilizing the active", "by stabilizing the active conformation.", "stabilizing the active conformation. tmd/jmd", "the active conformation. tmd/jmd mutants", "active conformation. tmd/jmd mutants that", "conformation. tmd/jmd mutants that are", "tmd/jmd mutants that are activating", "mutants that are activating in", "that are activating in the", "are activating in the presence", "activating in the presence of", "in the presence of wild", "the presence of wild type", "presence of wild type erbb2", "wild type erbb2 such", "type erbb2 such as", "erbb2 such as erbb2", "as erbb2 r678q may", "erbb2 r678q may form", "r678q may form homodimers", "may form homodimers with the", "form homodimers with the wild", "homodimers with the wild type", "with the wild type erbb2", "wild type erbb2 pahuja", "type erbb2 pahuja et", "erbb2 pahuja et al.", "pahuja et al. 2018 .

              based", "et al. 2018 .

              based on", "al. 2018 .

              based on trans", "2018 .

              based on trans autophosphorylation", ".

              based on trans autophosphorylation of", "on trans autophosphorylation of erbb2", "trans autophosphorylation of erbb2 and", "autophosphorylation of erbb2 and its", "of erbb2 and its dimerization", "erbb2 and its dimerization partners", "and its dimerization partners egfr", "its dimerization partners egfr and", "dimerization partners egfr and erbb3", "egfr and erbb3 the", "and erbb3 the following", "erbb3 the following erbb2", "the following erbb2 tmd/jmd mutants", "following erbb2 tmd/jmd mutants are", "erbb2 tmd/jmd mutants are assumed", "tmd/jmd mutants are assumed to", "mutants are assumed to form", "are assumed to form heterodimers", "assumed to form heterodimers with", "to form heterodimers with egfr", "form heterodimers with egfr and", "heterodimers with egfr and erbb3:
              erbb2", "with egfr and erbb3:
              erbb2 s653c", "and erbb3:
              erbb2 s653c de", "erbb3:
              erbb2 s653c de martino", "martino et al. 2014
              erbb2", "et al. 2014
              erbb2 r678q", "2014
              erbb2 r678q bose", "
              erbb2 r678q bose et", "r678q bose et al.", "et al. 2013 pahuja", "al. 2013 pahuja et", "2013 pahuja et al.", "pahuja et al. 2018 .

              phosphorylation", "et al. 2018 .

              phosphorylation of", "al. 2018 .

              phosphorylation of tyrosine", "2018 .

              phosphorylation of tyrosine residues", ".

              phosphorylation of tyrosine residues in", "of tyrosine residues in the", "tyrosine residues in the c", "residues in the c tail", "in the c tail of", "the c tail of erbb2", "c tail of erbb2 was", "tail of erbb2 was shown", "of erbb2 was shown for", "erbb2 was shown for the", "was shown for the following", "shown for the following erbb2", "for the following erbb2 tmd/jmd", "the following erbb2 tmd/jmd mutants:
              erbb2", "following erbb2 tmd/jmd mutants:
              erbb2 v659e", "tmd/jmd mutants:
              erbb2 v659e pahuja", "mutants:
              erbb2 v659e pahuja et", "v659e pahuja et al.", "et al. 2018
              erbb2", "al. 2018
              erbb2 v659k", "
              erbb2 v659k pahuja et", "v659k pahuja et al.", "al. 2018
              erbb2 g660d", "
              erbb2 g660d pahuja et", "g660d pahuja et al.", "al. 2018
              erbb2 g660r", "
              erbb2 g660r pahuja et", "g660r pahuja et al.", "al. 2018
              erbb2 s653c", "
              erbb2 s653c de martino", "al. 2014 phosphorylation", "2014 phosphorylation at", "at y1248 demonstrated
              erbb2", "y1248 demonstrated
              erbb2 r677l", "
              erbb2 r677l pahuja et", "r677l pahuja et al.", "al. 2018
              erbb2 r678q", "et al. 2013 de", "al. 2013 de martino", "2013 de martino et", "at y1248 demonstrated pahuja", "y1248 demonstrated pahuja et", "demonstrated pahuja et al.", "al. 2018 erbb2", "2018 erbb2 q709l", "erbb2 q709l pahuja et", "q709l pahuja et al.", "pahuja et al. 2018

              phosphorylation", "et al. 2018

              phosphorylation of", "al. 2018

              phosphorylation of tyrosine", "2018

              phosphorylation of tyrosine residues", "

              phosphorylation of tyrosine residues in", "the c tail of egfr", "c tail of egfr was", "tail of egfr was demonstrated", "of egfr was demonstrated for", "egfr was demonstrated for erbb2", "was demonstrated for erbb2 s653c", "for erbb2 s653c de", "erbb2 s653c de martino", "phosphorylation at y1068 and", "at y1068 and erbb2", "y1068 and erbb2 r678q", "and erbb2 r678q bose", "erbb2 r678q bose et", "phosphorylation at y1068 .

              phosphorylation of", "at y1068 .

              phosphorylation of tyrosine", "y1068 .

              phosphorylation of tyrosine residues", "the c tail of erbb3", "c tail of erbb3 was", "tail of erbb3 was demonstrated", "of erbb3 was demonstrated for", "erbb3 was demonstrated for erbb2", "phosphorylation at y1197 and", "at y1197 and erbb2", "y1197 and erbb2 r678q", "phosphorylation at y1197 .

              activation of", "at y1197 .

              activation of downstream", "y1197 .

              activation of downstream ras", ".

              activation of downstream ras signaling", "of downstream ras signaling was", "downstream ras signaling was shown", "ras signaling was shown for", "signaling was shown for erbb2", "was shown for erbb2 s653c", "et al. 2014 and", "al. 2014 and erbb2", "2014 and erbb2 r678q", "et al. 2014 through", "al. 2014 through activating", "2014 through activating tyrosine", "through activating tyrosine phosphorylation on", "activating tyrosine phosphorylation on erks", "phosphorylation on erks mapk1", "on erks mapk1 and", "erks mapk1 and mapk3", "mapk1 and mapk3 and", "and mapk3 and shc1.

              activation", "mapk3 and shc1.

              activation of", "and shc1.

              activation of downstream plcg1", "shc1.

              activation of downstream plcg1 signaling", "of downstream plcg1 signaling was", "downstream plcg1 signaling was demonstrated", "plcg1 signaling was demonstrated for", "signaling was demonstrated for erbb2", "was demonstrated for erbb2 r678q", "for erbb2 r678q through", "erbb2 r678q through activating", "r678q through activating tyrosine", "activating tyrosine phosphorylation on plcg1", "phosphorylation on plcg1 bose", "on plcg1 bose et", "plcg1 bose et al.", "bose et al. 2013 .

              activation", "et al. 2013 .

              activation of", "al. 2013 .

              activation of pi3k/akt", "2013 .

              activation of pi3k/akt signaling", ".

              activation of pi3k/akt signaling by", "of pi3k/akt signaling by erbb2", "pi3k/akt signaling by erbb2 tmd/jmd", "by erbb2 tmd/jmd mutants has", "erbb2 tmd/jmd mutants has not", "tmd/jmd mutants has not been", "mutants has not been tested.

              signaling", "has not been tested.

              signaling by", "not been tested.

              signaling by erbb2", "been tested.

              signaling by erbb2 v659k", "by erbb2 v659k erbb2", "erbb2 g660r erbb2 r677l", "erbb2 r677l erbb2 e693k", "r677l erbb2 e693k and", "erbb2 e693k and erbb2 q709l", "e693k and erbb2 q709l has", "and erbb2 q709l has not", "erbb2 q709l has not been", "q709l has not been sufficiently", "has not been sufficiently studied", "not been sufficiently studied and", "been sufficiently studied and they", "sufficiently studied and they are", "studied and they are annotated", "and they are annotated as", "they are annotated as candidates.

              the", "are annotated as candidates.

              the following", "annotated as candidates.

              the following erbb2", "as candidates.

              the following erbb2 tmd/jmd", "candidates.

              the following erbb2 tmd/jmd mutants", "erbb2 tmd/jmd mutants are sensitive", "tmd/jmd mutants are sensitive to", "are sensitive to the", "sensitive to the therapeutic", "to the therapeutic antibody", "therapeutic antibody trastuzumab herceptin", "antibody trastuzumab herceptin :
              erbb2", "trastuzumab herceptin :
              erbb2 v659e", "herceptin :
              erbb2 v659e pahuja", ":
              erbb2 v659e pahuja et", "al. 2018
              erbb2 q709l", "
              erbb2 q709l pahuja et", "et al. 2018

              with", "al. 2018

              with respect", "2018

              with respect to", "respect to pertuzumab a", "to pertuzumab a therapeutic", "pertuzumab a therapeutic antibody", "a therapeutic antibody that block", "therapeutic antibody that block ligand", "antibody that block ligand driven", "that block ligand driven heterodimerization", "block ligand driven heterodimerization of", "ligand driven heterodimerization of erbb2", "heterodimerization of erbb2 erbb2", "of erbb2 erbb2 r678q", "erbb2 erbb2 r678q is", "erbb2 r678q is sensitive to", "r678q is sensitive to pertuzumab", "sensitive to pertuzumab while", "to pertuzumab while erbb2", "pertuzumab while erbb2 v659e", "while erbb2 v659e erbb2", "g660d erbb2 g660r and", "erbb2 g660r and probably erbb2", "g660r and probably erbb2 q709l", "and probably erbb2 q709l are", "probably erbb2 q709l are resistant", "q709l are resistant pahuja", "are resistant pahuja et", "resistant pahuja et al.", "pahuja et al. 2018 .

              the", "et al. 2018 .

              the following", "al. 2018 .

              the following erbb2", "2018 .

              the following erbb2 tmd/jmd", ".

              the following erbb2 tmd/jmd mutants", "mutants are sensitive to lapatinib:
              erbb2", "are sensitive to lapatinib:
              erbb2 s653c", "to lapatinib:
              erbb2 s653c de", "lapatinib:
              erbb2 s653c de martino", "et al. 2013

              the", "al. 2013

              the following", "2013

              the following erbb2", "

              the following erbb2 tmd/jmd mutants", "mutants are sensitive to neratinib:
              erbb2", "are sensitive to neratinib:
              erbb2 v659e", "to neratinib:
              erbb2 v659e pahuja", "neratinib:
              erbb2 v659e pahuja et", "et al. 2018

              the", "al. 2018

              the following", "2018

              the following erbb2", "mutants are sensitive to afatinib:
              erbb2", "are sensitive to afatinib:
              erbb2 g660d", "to afatinib:
              erbb2 g660d pahuja", "afatinib:
              erbb2 g660d pahuja et", "
              erbb2 r678q pahuja et", "r678q pahuja et al." ] }, { "record_id": "GLY_000594_1_2005", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9670095", "r hsa", "hsa 9670095", "r hsa 9670095" ] }, { "record_id": "GLY_000594_1_2005", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "inhibition of", "of dna", "dna recombination", "recombination at", "at telomere", "inhibition of dna", "of dna recombination", "dna recombination at", "recombination at telomere", "inhibition of dna recombination", "of dna recombination at", "dna recombination at telomere", "inhibition of dna recombination at", "of dna recombination at telomere", "telomeres resemble", "resemble double", "double strand", "strand dna", "dna breaks", "if not", "not properly", "properly packaged", "packaged and", "and protected", "are recognized", "recognized by", "by the", "the dna", "dna double", "strand break", "break repair", 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alt .", "telomeres alt . alt", "alt . alt occurs in", ". alt occurs in about", "alt occurs in about 5", "occurs in about 5 15%", "in about 5 15% of", "about 5 15% of cancers", "5 15% of cancers and", "15% of cancers and is", "of cancers and is a", "cancers and is a telomerase", "and is a telomerase independent", "is a telomerase independent mechanism", "a telomerase independent mechanism of", "telomerase independent mechanism of replicative", "independent mechanism of replicative immortality.", "mechanism of replicative immortality. for", "of replicative immortality. for review", "immortality. for review please", "for review please refer", "review please refer to", "please refer to arnoult and", "refer to arnoult and karlseder", "to arnoult and karlseder 2015", "arnoult and karlseder 2015 and", "and karlseder 2015 and pickett", "karlseder 2015 and pickett and", "2015 and pickett and reddel", "and pickett and reddel 2015." ] }, { "record_id": "GLY_000594_1_2006", "filename": 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within", "within main", "main host", "host macrophages", "2017 .", ". in", "in addition", "wnt5 is", "is a", "highly responsive", "responsive gene", "in human", "human macrophages", "macrophages present", "present in", "in chronic", "chronic diseases", "diseases such", "such as", "as rheumatoid", "rheumatoid arthritis", "sen et", "al. 2000", "pukrop et", "christman et", "and obesity", "ouchi et", "al. 2010", "2010 &", "2019 .

              frizzled", ".

              frizzled 7", "acts as", "as a", "a receptor", "receptor of", "of wnt5", "wnt5 which", "upon binding", "is implicated", "implicated in", "in the", "the initiation", "initiation of", "of the", "the non", "non canonical", "canonical wnt", "wnt pathway", "pathway that", "that ends", "ends up", "up in", "the re", "re accommodation", "accommodation of", "the cytoskeleton", "cytoskeleton to", "to allow", "allow a", "a process", "process called", "called planar", "planar cell", "cell polarity", "2019 .", ". the", "the activation", "activation of", "the wnt5:fzd7", "wnt5:fzd7 non", "canonical signalling", "signalling cascade", "cascade that", "that drives", "drives pcp", "pcp is", "is being", "being studied", "studied for", "for its", "its involvement", "involvement in", "in inflammatory", "inflammatory responses", "shao et", "al. 2016", "2016 .", ". treatment", "treatment of", "of raw264.7", "raw264.7 macrophages", "macrophages with", "with recombinant", "recombinant wnt5a", "wnt5a induced", "induced nadph", "nadph oxidase", "oxidase mediated", "mediated ros", "ros production", "which has", "has been", "been suggested", "suggested to", "to contribute", "contribute to", "to the", "the macrophage", "macrophage control", "control of", "of l.", "l. donovani.", "donovani. consequently", "detailed understanding", "understanding of", "of how", "how wnt", "wnt signaling", "signaling network", "network defines", "defines host", "host responses", "responses to", "to infection", "infection could", "could be", "be important", "important to", "to identify", "identify potential", "potential targets", "5a wnt5", "is known for", "known for being", "for being a", "being a highly", "a highly specific", "highly specific regulated", "specific regulated gene", "regulated gene in", "gene in response", "in response to", "response to microbial", "to microbial infection", "infection blumenthal", "blumenthal et al.", "et al. 2006", "2006 pereira", "pereira et al.", "et al. 2008", "al. 2008 &", "2008 & ljungberg", "& ljungberg et", "ljungberg et al.", "et al. 2019", "2019 including", "leishmaniasis chakraborty", "chakraborty et al.", "et al. 2017", "where it seems", "it seems to", "seems to be", "to be involve", "be involve in", "involve in mechanisms", "in mechanisms that", "mechanisms that dampen", "that dampen the", "dampen the parasite", "the parasite load", "parasite load within", "load within main", "within main host", "main host macrophages", "macrophages chakraborty", "al. 2017 .", "2017 . in", ". in addition", "addition wnt5", "wnt5 is a", "is a highly", "a highly responsive", "highly responsive gene", "responsive gene in", "gene in human", "in human macrophages", "human macrophages present", "macrophages present in", "present in chronic", "in chronic diseases", "chronic diseases such", "diseases such as", "such as rheumatoid", "as rheumatoid arthritis", "arthritis sen", "sen et al.", "et al. 2000", "cancer pukrop", "pukrop et al.", "atherosclerosis christman", "christman et al.", "2008 and", "obesity ouchi", "ouchi et al.", "et al. 2010", "al. 2010 &", "2010 & ljungberg", "al. 2019 .

              frizzled", "2019 .

              frizzled 7", "7 fzd7", "fzd7 acts", "acts as a", "as a receptor", "a receptor of", "receptor of wnt5", "of wnt5 which", "which upon", "binding is", "is implicated in", "implicated in the", "in the initiation", "the initiation of", "initiation of the", "of the non", "the non canonical", "non canonical wnt", "canonical wnt pathway", "wnt pathway that", "pathway that ends", "that ends up", "ends up in", "up in the", "in the re", "the re accommodation", "re accommodation of", "accommodation of the", "of the cytoskeleton", "the cytoskeleton to", "cytoskeleton to allow", "to allow a", "allow a process", "a process called", "process called planar", "called planar cell", "planar cell polarity", "polarity pcp", "al. 2019 .", "2019 . the", ". the activation", "the activation of", "activation of the", "of the wnt5:fzd7", "the wnt5:fzd7 non", "wnt5:fzd7 non canonical", "non canonical signalling", "canonical signalling cascade", "signalling cascade that", "cascade that drives", "that drives pcp", "drives pcp is", "pcp is being", "is being studied", "being studied for", "studied for its", "for its involvement", "its involvement in", "involvement in inflammatory", "in inflammatory responses", "responses shao", "shao et al.", "et al. 2016", "al. 2016 .", "2016 . treatment", ". treatment of", "treatment of raw264.7", "of raw264.7 macrophages", "raw264.7 macrophages with", "macrophages with recombinant", "with recombinant wnt5a", "recombinant wnt5a induced", "wnt5a induced nadph", "induced nadph oxidase", "nadph oxidase mediated", "oxidase mediated ros", "mediated ros production", "production which", "which has been", "has been suggested", "been suggested to", "suggested to contribute", "to contribute to", "contribute to the", "to the macrophage", "the macrophage control", "macrophage control of", "control of l.", "of l. donovani.", "l. donovani. consequently", "consequently detailed", "detailed understanding of", "understanding of how", "of how wnt", "how wnt signaling", "wnt signaling network", "signaling network defines", "network defines host", "defines host responses", "host responses to", "responses to infection", "to infection could", "infection could be", "could be important", "be important to", "important to identify", "to identify potential", "identify potential targets", "targets ljungberg", "wnt 5a wnt5", "wnt5 is known", "is known for being", "known for being a", "for being a highly", "being a highly specific", "a highly specific regulated", "highly specific regulated gene", "specific regulated gene in", "regulated gene in response", "gene in response to", "in response to microbial", "response to microbial infection", "microbial infection blumenthal", "infection blumenthal et", "blumenthal et al. 2006", "al. 2006 pereira", "2006 pereira et", "pereira et al. 2008", "et al. 2008 &", "al. 2008 & ljungberg", "2008 & ljungberg et", "& ljungberg et al.", "ljungberg et al. 2019", "al. 2019 including", "2019 including leishmaniasis", "including leishmaniasis chakraborty", "leishmaniasis chakraborty et", "chakraborty et al. 2017", "2017 where", "where it seems to", "it seems to be", "seems to be involve", "to be involve in", "be involve in mechanisms", "involve in mechanisms that", "in mechanisms that dampen", "mechanisms that dampen the", "that dampen the parasite", "dampen the parasite load", "the parasite load within", "parasite load within main", "load within main host", "within main host macrophages", "host macrophages chakraborty", "macrophages chakraborty et", "et al. 2017 .", "al. 2017 . in", "2017 . in addition", "in addition wnt5", "addition wnt5 is", "wnt5 is a highly", "is a highly responsive", "a highly responsive gene", "highly responsive gene in", "responsive gene in human", "gene in human macrophages", "in human macrophages present", "human macrophages present in", "macrophages present in chronic", "present in chronic diseases", "in chronic diseases such", "chronic diseases such as", "diseases such as rheumatoid", "such as rheumatoid arthritis", "rheumatoid arthritis sen", "arthritis sen et", "sen et al. 2000", "2000 cancer", "cancer pukrop et", "pukrop et al. 2006", "2006 atherosclerosis", "atherosclerosis christman et", "christman et al. 2008", "al. 2008 and", "2008 and obesity", "and obesity ouchi", "obesity ouchi et", "ouchi et al. 2010", "et al. 2010 &", "al. 2010 & ljungberg", "2010 & ljungberg et", "et al. 2019 .

              frizzled", "al. 2019 .

              frizzled 7", ".

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the activation of", "the activation of the", "activation of the wnt5:fzd7", "of the wnt5:fzd7 non", "the wnt5:fzd7 non canonical", "wnt5:fzd7 non canonical signalling", "non canonical signalling cascade", "canonical signalling cascade that", "signalling cascade that drives", "cascade that drives pcp", "that drives pcp is", "drives pcp is being", "pcp is being studied", "is being studied for", "being studied for its", "studied for its involvement", "for its involvement in", "its involvement in inflammatory", "involvement in inflammatory responses", "inflammatory responses shao", "responses shao et", "shao et al. 2016", "et al. 2016 .", "al. 2016 . treatment", "2016 . treatment of", ". treatment of raw264.7", "treatment of raw264.7 macrophages", "of raw264.7 macrophages with", "raw264.7 macrophages with recombinant", "macrophages with recombinant wnt5a", "with recombinant wnt5a induced", "recombinant wnt5a induced nadph", "wnt5a induced nadph oxidase", "induced nadph oxidase mediated", "nadph oxidase mediated ros", "oxidase mediated ros production", "ros production which", "production which has", "which has been suggested", "has been suggested to", "been suggested to contribute", "suggested to contribute to", "to contribute to the", "contribute to the macrophage", "to the macrophage control", "the macrophage control of", "macrophage control of l.", "control of l. donovani.", "of l. donovani. consequently", "donovani. consequently detailed", "consequently detailed understanding", "detailed understanding of how", "understanding of how wnt", "of how wnt signaling", "how wnt signaling network", "wnt signaling network defines", "signaling network defines host", "network defines host responses", "defines host responses to", "host responses to infection", "responses to infection could", "to infection could be", "infection could be important", "could be important to", "be important to identify", "important to identify potential", "to identify potential targets", "potential targets ljungberg", "targets ljungberg et", "5a wnt5 is", "wnt5 is known for", "is known for being a", "known for being a highly", "for being a highly specific", "being a highly specific regulated", "a highly specific regulated gene", "highly specific regulated gene in", "specific regulated gene in response", "regulated gene in response to", "gene in response to microbial", "in response to microbial infection", "to microbial infection blumenthal", "microbial infection blumenthal et", "infection blumenthal et al.", "et al. 2006 pereira", "al. 2006 pereira et", "2006 pereira et al.", "pereira et al. 2008 &", "et al. 2008 & ljungberg", "al. 2008 & ljungberg et", "2008 & ljungberg et al.", "& ljungberg et al. 2019", "et al. 2019 including", "al. 2019 including leishmaniasis", "including leishmaniasis chakraborty et", "leishmaniasis chakraborty et al.", "al. 2017 where", "2017 where it", "where it seems to be", "it seems to be involve", "seems to be involve in", "to be involve in 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rheumatoid", "diseases such as rheumatoid arthritis", "as rheumatoid arthritis sen", "rheumatoid arthritis sen et", "arthritis sen et al.", "al. 2000 cancer", "cancer pukrop et al.", "al. 2006 atherosclerosis", "atherosclerosis christman et al.", "et al. 2008 and", "al. 2008 and obesity", "and obesity ouchi et", "obesity ouchi et al.", "ouchi et al. 2010 &", "et al. 2010 & ljungberg", "al. 2010 & ljungberg et", "2010 & ljungberg et al.", "ljungberg et al. 2019 .

              frizzled", "et al. 2019 .

              frizzled 7", "2019 .

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cell", "process called planar cell polarity", "planar cell polarity pcp", "pcp ljungberg et", "ljungberg et al. 2019 .", "et al. 2019 . the", "al. 2019 . the activation", "2019 . the activation of", ". the activation of the", "the activation of the wnt5:fzd7", "activation of the wnt5:fzd7 non", "of the wnt5:fzd7 non canonical", "the wnt5:fzd7 non canonical signalling", "wnt5:fzd7 non canonical signalling cascade", "non canonical signalling cascade that", "canonical signalling cascade that drives", "signalling cascade that drives pcp", "cascade that drives pcp is", "that drives pcp is being", "drives pcp is being studied", "pcp is being studied for", "is being studied for its", "being studied for its involvement", "studied for its involvement in", "for its involvement in inflammatory", "its involvement in inflammatory responses", "in inflammatory responses shao", "inflammatory responses shao et", "responses shao et al.", "shao et al. 2016 .", "et al. 2016 . treatment", "al. 2016 . 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"consequently detailed understanding of", "detailed understanding of how wnt", "understanding of how wnt signaling", "of how wnt signaling network", "how wnt signaling network defines", "wnt signaling network defines host", "signaling network defines host responses", "network defines host responses to", "defines host responses to infection", "host responses to infection could", "responses to infection could be", "to infection could be important", "infection could be important to", "could be important to identify", "be important to identify potential", "important to identify potential targets", "identify potential targets ljungberg", "potential targets ljungberg et", "targets ljungberg et al." ] }, { "record_id": "GLY_000594_1_2008", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9673767", "r hsa", "hsa 9673767", "r hsa 9673767" ] }, { "record_id": "GLY_000594_1_2008", "filename": "human_protein_pathways_reactome", "fieldtype": 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              pdgfra", ".
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lobe of", "small lobe of the", "lobe of the kinase", "of the kinase domain", "the kinase domain and", "kinase domain and d842", "domain and d842 in", "and d842 in the", "d842 in the activation", "in the activation loop", "the activation loop of", "activation loop of the", "loop of the kinase", "of the kinase domain.", "the kinase domain. pdgfra", "kinase domain. pdgfra is", "domain. pdgfra is also", "pdgfra is also subject", "is also subject to", "also subject to short", "subject to short deletions", "to short deletions in", "short deletions in the", "deletions in the activation", "the activation loop segment", "loop segment reviewed", "segment reviewed in", "in roskoski 2018", "2018 . acitvated forms", ". acitvated forms of", "acitvated forms of the", "forms of the protein", "of the protein may", "the protein may signal", "protein may signal from", "may signal from the", "signal from the plasma", "from the plasma membrane", "plasma membrane similar", "membrane similar to", "similar to the wild", "to the wild type", "the wild type receptor", "type receptor however", "receptor however there", "however there is also", "there is also evidence", "is also evidence that", "also evidence that some", "evidence that some mutants", "some mutants notably", "mutants notably d842v", "notably d842v and v561d", "d842v and v561d localize", "and v561d localize primarily", "v561d localize primarily to", "localize primarily to the", "primarily to the golgi", "to the golgi membrane", "golgi membrane bahlawane", "membrane bahlawane et", "et al 2014", "al 2014 .", "2014 . activated pdgfra", ". activated pdgfra mutants", "activated pdgfra mutants signal", "pdgfra mutants signal constitutively", "mutants signal constitutively in", "signal constitutively in the", "constitutively in the absence", "of ligand reviewed", "ligand reviewed in", "2018 wang et", "2016 klug et", "pdgfra is a type iii", "a type iii transmembrane", "type iii transmembrane receptor", "iii transmembrane receptor tyrosine", "transmembrane receptor tyrosine kinase. the", "receptor tyrosine kinase. the extracellular", "tyrosine kinase. the extracellular domain", "kinase. the extracellular domain consists", "the extracellular domain consists of", "extracellular domain consists of 5", "domain consists of 5 immunoglobulin", "of 5 immunoglobulin ig", "immunoglobulin ig domains", "ig domains that contribute", "domains that contribute to dimerization", "that contribute to dimerization and", "contribute to dimerization and ligand", "to dimerization and ligand binding.", "dimerization and ligand binding. the", "and ligand binding. the intracellular", "ligand binding. the intracellular region", "binding. the intracellular region has", "the intracellular region has a", "intracellular region has a juxtamembrane", "region has a juxtamembrane domain", "has a juxtamembrane domain that", "a juxtamembrane domain that plays", "juxtamembrane domain that plays a", "domain that plays a role", "that plays a role in", "plays a role in autoinhibiting", "a role in autoinhibiting the", "role in autoinhibiting the receptor", "in autoinhibiting the receptor in", "autoinhibiting the receptor in the", "the receptor in the absence", "receptor in the absence of", "in the absence of ligand", "absence of ligand and", "of ligand and a", "ligand and a bi", "and a bi lobed kinase", "a bi lobed kinase region", "bi lobed kinase region with", "lobed kinase region with an", "kinase region with an activation", "region with an activation loop", "with an activation loop and", "an activation loop and the", "activation loop and the catalytic", "loop and the catalytic cleft", "the catalytic cleft reviewed", "catalytic cleft reviewed in", "cleft reviewed in klug", "reviewed in klug et al", "klug et al 2018", "et al 2018 .", "al 2018 . upon", "2018 . upon ligand binding", "upon ligand binding pdgfra", "ligand binding pdgfra undergoes", "binding pdgfra undergoes dimerization", "pdgfra undergoes dimerization and transautophosphorylation", "undergoes dimerization and transautophosphorylation at", "dimerization and transautophosphorylation at at", "and transautophosphorylation at at least", "transautophosphorylation at at least 11", "at at least 11 tyrosine", "at least 11 tyrosine residues", "least 11 tyrosine residues in", "11 tyrosine residues in the", "tyrosine residues in the intracellular", "residues in the intracellular domain.", "in the intracellular domain. these", "the intracellular domain. these phosphorylated", "intracellular domain. these phosphorylated residues", "domain. these phosphorylated residues are", "these phosphorylated residues are binding", "phosphorylated residues are binding sites", "residues are binding sites for", "are binding sites for downstream", "binding sites for downstream effectors", "sites for downstream effectors of", "for downstream effectors of pdgfra", "downstream effectors of pdgfra responsive", "effectors of pdgfra responsive signaling", "of pdgfra responsive signaling pathways", "responsive signaling pathways reviewed", "signaling pathways reviewed in", "pathways reviewed in klug", "al 2018 roskoski", "2018 roskoski 2018", "roskoski 2018 .
              pdgfra", "2018 .
              pdgfra is subject", ".
              pdgfra is subject to", "
              pdgfra is subject to activating", "is subject to activating mutations", "subject to activating mutations in", "to activating mutations in a", "activating mutations in a number", "mutations in a number of", "in a number of cancers", "number of cancers including", "of cancers including gastrointestinal", "cancers including gastrointestinal stromal", "gastrointestinal stromal tumors gist", "gist melanoma and", "and haematological cancers reviewed", "haematological cancers reviewed in", "cancers reviewed in corless", "reviewed in corless et al", "corless et al 2011", "al 2011 wang", "2011 wang et al", "wang et al 2016", "al 2016 roskoski", "2016 roskoski 2018", "roskoski 2018 . the", "2018 . the most prevalent", ". the most prevalent mutations", "the most prevalent mutations in", "most prevalent mutations in pdgfra", "prevalent mutations in pdgfra are", "mutations in pdgfra are at", "in pdgfra are at residue", "pdgfra are at residue v561", "are at residue v561 in", "at residue v561 in the", "residue v561 in the juxtamembrane", "v561 in the juxtamembrane domain", "the juxtamembrane domain n659", "juxtamembrane domain n659 in", "domain n659 in the", "n659 in the small lobe", "in the small lobe of", "the small lobe of the", "small lobe of the kinase", "lobe of the kinase domain", "of the kinase domain and", "the kinase domain and d842", "kinase domain and d842 in", "domain and d842 in the", "and d842 in the activation", "d842 in the activation loop", "in the activation loop of", "the activation loop of the", "activation loop of the kinase", "loop of the kinase domain.", "of the kinase domain. pdgfra", "the kinase domain. pdgfra is", "kinase domain. pdgfra is also", "domain. pdgfra is also subject", "pdgfra is also subject to", "is also subject to short", "also subject to short deletions", "subject to short deletions in", "to short deletions in the", "short deletions in the activation", "deletions in the activation loop", "in the activation loop segment", "activation loop segment reviewed", "loop segment reviewed in", "segment reviewed in roskoski", "reviewed in roskoski 2018", "in roskoski 2018 .", "roskoski 2018 . acitvated", "2018 . acitvated forms of", ". acitvated forms of the", "acitvated forms of the protein", "forms of the protein may", "of the protein may signal", "the protein may signal from", "protein may signal from the", "may signal from the plasma", "signal from the plasma membrane", "the plasma membrane similar", "plasma membrane similar to", "membrane similar to the", "similar to the wild type", "to the wild type receptor", "wild type receptor however", "type receptor however there", "receptor however there is", "however there is also evidence", "there is also evidence that", "is also evidence that some", "also evidence that some mutants", "that some mutants notably", "some mutants notably d842v", "mutants notably d842v and", "notably d842v and v561d localize", "d842v and v561d localize primarily", "and v561d localize primarily to", "v561d localize primarily to the", "localize primarily to the golgi", "primarily to the golgi membrane", "the golgi membrane bahlawane", "golgi membrane bahlawane et", "membrane bahlawane et al", "bahlawane et al 2014", "et al 2014 .", "al 2014 . activated", "2014 . activated pdgfra mutants", ". activated pdgfra mutants signal", "activated pdgfra mutants signal constitutively", "pdgfra mutants signal constitutively in", "mutants signal constitutively in the", "signal constitutively in the absence", "constitutively in the absence of", "absence of ligand reviewed", "of ligand reviewed in", "ligand reviewed in roskoski", "roskoski 2018 wang", "2018 wang et al", "al 2016 klug", "2016 klug et al" ] }, { "record_id": "GLY_000594_1_2009", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9673770", "r hsa", "hsa 9673770", "r hsa 9673770" ] }, { "record_id": "GLY_000594_1_2009", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by pdgfra", "pdgfra extracellular", "extracellular domain", "domain mutants", "signaling by pdgfra", "by pdgfra extracellular", "pdgfra extracellular domain", "extracellular domain mutants", "signaling by pdgfra extracellular", "by pdgfra extracellular domain", "pdgfra extracellular domain mutants", "signaling by pdgfra extracellular domain", "by pdgfra extracellular domain mutants", "mutations in", "in the", "the extracellular", "domain of", "of receptor", "receptor tyrosine", "tyrosine kinases", "kinases like", "like pdgrfa", "pdgrfa have", "have the", "the potential", "potential to", "to interfere", "interfere with", "with glycosylation", "which is", "is required", "required for", "for proper", "proper trafficking", "trafficking to", "to the", "the cell", "cell surface.", "surface. versions", "versions of", "of pdgfra", "pdgfra bearing", "bearing mutations", "domain have", "have been", "been 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et", "et al 2018", "2018 velghe et", "et al 2014", "2014 ozawa et", "et al 2010", "2010 paugh et", "et al 2013", "2013 clarke et", "et al 2003", "al 2003 .", "2003 . pdgfra y288c", ". pdgfra y288c carries", "pdgfra y288c carries a", "y288c carries a mutation", "carries a mutation in", "a mutation in the", "mutation in the extracellular", "extracellular domain of the", "domain of the receptor", "of the receptor that", "the receptor that prevents", "receptor that prevents the", "that prevents the normal", "prevents the normal trafficking", "the normal trafficking of", "normal trafficking of the", "trafficking of the protein", "of the protein to", "the protein to the", "protein to the plasma", "to the plasma membrane.", "the plasma membrane. pdgfra", "plasma membrane. pdgfra y288c", "membrane. pdgfra y288c is", "pdgfra y288c is trapped", "y288c is trapped in", "is trapped in the", "trapped in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum membrane", 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              molecular features of the vgf", "features of the vgf signaling", "of the vgf signaling cascades", "the vgf signaling cascades are", "vgf signaling cascades are outlined", "signaling cascades are outlined in", "cascades are outlined in the", "are outlined in the figure", "outlined in the figure below", "the figure below from", "figure below from olsson", "below from olsson et", "from olsson et al. 2006", "et al. 2006 nature", "al. 2006 nature publishing", "2006 nature publishing group", "nature publishing group . tyrosine", "publishing group . tyrosine residues", "group . tyrosine residues in", ". tyrosine residues in the", "tyrosine residues in the intracellular", "residues in the intracellular domains", "in the intracellular domains of", "the intracellular domains of vegf", "intracellular domains of vegf receptors", "domains of vegf receptors 1", "vegf receptors 1 2", "receptors 1 2 and", "1 2 and 3", "2 and 3 are indicated", "and 3 are indicated by", "3 are indicated by dark", "are indicated by dark blue", "indicated by dark blue boxes", "dark blue boxes residues", "blue boxes residues susceptible", "boxes residues susceptible to", "residues susceptible to phosphorylation are", "susceptible to phosphorylation are numbered.", "to phosphorylation are numbered. a", "phosphorylation are numbered. a circled", "are numbered. a circled r", "numbered. a circled r indicates", "a circled r indicates that", "circled r indicates that phosphorylation", "r indicates that phosphorylation is", "indicates that phosphorylation is regulated", "that phosphorylation is regulated by", "phosphorylation is regulated by cell", "is regulated by cell state", "by cell state vegfr2", "vegfr2 by ligand", "by ligand binding vegfr1", "vegfr1 or by", "or by heterodimerization vegfr3", "by heterodimerization vegfr3 .", "heterodimerization vegfr3 . specific", "vegfr3 . specific phosphorylation sites", "specific phosphorylation sites boxed", "phosphorylation sites boxed numbers", "boxed numbers bind signaling", "numbers bind signaling molecules", "bind signaling molecules dark", "signaling molecules dark blue", "molecules dark blue ovals", "blue ovals whose", "ovals whose interaction", "whose interaction with other cytosolic", "interaction with other cytosolic signaling", "with other cytosolic signaling molecules", "cytosolic signaling molecules light", "signaling molecules light blue", "molecules light blue ovals", "light blue ovals leads", "blue ovals leads to", "ovals leads to specific", "to specific cellular pale", "specific cellular pale blue", "cellular pale blue boxes", "pale blue boxes and", "blue boxes and tissue", "boxes and tissue level", "and tissue level pink", "tissue level pink boxes", "pink boxes responses in", "boxes responses in vivo.", "responses in vivo. signaling cascades", "in vivo. signaling cascades whose", "vivo. signaling cascades whose molecular", "signaling cascades whose molecular details", "cascades whose molecular details are", "whose molecular details are unclear", "molecular details are unclear are", "details are unclear are indicated", "are unclear are indicated by", "unclear are indicated by dashed", "are indicated by dashed arrows.", "indicated by dashed arrows. dag", "dashed arrows. dag diacylglycerol", "dag diacylglycerol ec", "diacylglycerol ec endothelial", "cell enos endothelial", "enos endothelial nitric oxide", "nitric oxide synthase fak", "synthase fak focal", "fak focal adhesion kinase", "focal adhesion kinase hpc", "kinase hpc hematopoietic", "hpc hematopoietic progenitor cell", "hematopoietic progenitor cell hsp27", "cell hsp27 heat", "hsp27 heat shock protein", "shock protein 27 mapk", "27 mapk mitogen", "mapk mitogen activated protein", "activated protein kinase mek", "kinase mek mapk", "mek mapk and erk", "and erk kinase pi3k", "kinase pi3k phosphatidylinositol", "pi3k phosphatidylinositol 3' kinase", "phosphatidylinositol 3' kinase pkc", "kinase pkc protein", "pkc protein kinase c", "protein kinase c plcgamma", "c plcgamma phospholipase", "plcgamma phospholipase c gamma", "phospholipase c gamma shb", "gamma shb sh2", "shb sh2 and beta", "and beta cells tsad", "cells tsad t", "tsad t cell specific", "t cell specific adaptor.
              in the", "cell specific adaptor.
              in the current", "specific adaptor.
              in the current release", "the current release the", "current release the first", "release the first events", "the first events in these", "first events in these cascades", "these cascades the", "cascades the interactions", "the interactions between vegf proteins", "interactions between vegf proteins and", "between vegf proteins and their", "vegf proteins and their receptors", "their receptors are", "receptors are annotated." ] }, { "record_id": "GLY_000594_1_2014", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9661070", "r hsa", "hsa 9661070", "r hsa 9661070" ] }, { "record_id": "GLY_000594_1_2014", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective translocation", "translocation of", "of rb1", "rb1 mutants", "mutants to", "to the", "the nucleus", "defective translocation of", "translocation of rb1", "of rb1 mutants", "rb1 mutants to", "mutants to the", "to the nucleus", "defective translocation of rb1", "translocation of rb1 mutants", "of rb1 mutants to", "rb1 mutants to the", "mutants to the nucleus", "defective translocation of rb1 mutants", "translocation of rb1 mutants to", "of rb1 mutants to the", "rb1 mutants to the nucleus", "this pathway", "pathway describes", "describes impaired", "impaired nuclear", "nuclear localization", "localization of", "mutants that", "that lack", "lack the", "the nuclear", "localization signal", "zacksenhaus et", "et al.", "al. 1993", "bremner et", "al. 1997", "1997 .", "this pathway describes", "pathway describes impaired", "describes impaired nuclear", "impaired nuclear localization", "nuclear localization of", "localization of rb1", "rb1 mutants that", "mutants that lack", "that lack the", "lack the nuclear", "the nuclear localization", "nuclear localization signal", "signal nls", "zacksenhaus et al.", "et al. 1993", "1993 bremner", "bremner et al.", "et al. 1997", "al. 1997 .", "this pathway describes impaired", "pathway describes impaired nuclear", "describes impaired nuclear localization", "impaired nuclear localization of", "nuclear localization of rb1", "localization of rb1 mutants", "of rb1 mutants that", "rb1 mutants that lack", "mutants that lack the", "that lack the nuclear", "lack the nuclear localization", "the nuclear localization signal", "localization signal nls", "nls zacksenhaus", "zacksenhaus et al. 1993", "al. 1993 bremner", "1993 bremner et", "bremner et al. 1997", "et al. 1997 .", "this pathway describes impaired nuclear", "pathway describes impaired nuclear localization", "describes impaired nuclear localization of", "impaired nuclear localization of rb1", "nuclear localization of rb1 mutants", "localization of rb1 mutants that", "of rb1 mutants that lack", "rb1 mutants that lack the", "mutants that lack the nuclear", "that lack the nuclear localization", "lack the nuclear localization signal", "nuclear localization signal nls", "nls zacksenhaus et", "et al. 1993 bremner", "al. 1993 bremner et", "1993 bremner et al.", "bremner et al. 1997 ." ] }, { "record_id": "GLY_000594_1_2015", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9662834", "r hsa", "hsa 9662834", "r hsa 9662834" ] }, { "record_id": "GLY_000594_1_2015", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cd163 mediating", "mediating an", "an anti", "anti inflammatory", "inflammatory response", "cd163 mediating an", "mediating an anti", "an anti inflammatory", "anti inflammatory response", "cd163 mediating an anti", "mediating an anti inflammatory", "an anti inflammatory response", "cd163 mediating an anti inflammatory", "mediating an anti inflammatory response", "high expression", "expression of", "of the", "the membrane", "membrane protein", "protein cd163", "cd163 in", "in macrophages", "macrophages is", "is a", "a characteristic", "characteristic of", "of tissues", "tissues responding", "responding 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              primary mutations", ".

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              primary", "2018 .

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              primary", "al 2018 .

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like", "fifth ig like domain", "like domain encoded", "domain encoded by", "encoded by exon 8", "by exon 8 and", "exon 8 and 9.", "8 and 9. the", "and 9. the fifth", "9. the fifth ig", "ig like domain of", "like domain of kit", "domain of kit plays", "of kit plays a", "kit plays a critical", "plays a critical role", "a critical role in", "critical role in stabilizing", "role in stabilizing the", "in stabilizing the receptor", "stabilizing the receptor dimers", "the receptor dimers formed", "receptor dimers formed upon", "dimers formed upon scf", "formed upon scf binding", "scf binding allowing", "binding allowing these", "allowing these mutations to", "these mutations to support", "mutations to support constitutive", "to support constitutive activation", "support constitutive activation of", "constitutive activation of the", "activation of the receptor", "the receptor yuzawa", "receptor yuzawa et", "et al 2007", "2007 reviewed in", "reviewed in lennartsson and", "in lennartsson and ronnstrand", "and ronnstrand 2012", "many of the described kit", "of the described kit mutations", "the described kit mutations are", "described kit mutations are located", "kit mutations are located in", "mutations are located in the", "are located in the fifth", "located in the fifth ig", "in the fifth ig like", "the fifth ig like domain", "ig like domain encoded", "like domain encoded by", "domain encoded by exon", "encoded by exon 8 and", "by exon 8 and 9.", "exon 8 and 9. the", "8 and 9. the fifth", "and 9. the fifth ig", "9. the fifth ig like", "fifth ig like domain of", "ig like domain of kit", "like domain of kit plays", "domain of kit plays a", "of kit plays a critical", "kit plays a critical role", "plays a critical role in", "a critical role in stabilizing", "critical role in stabilizing the", "role in stabilizing the receptor", "in stabilizing the receptor dimers", "stabilizing the receptor dimers formed", "the receptor dimers formed upon", "receptor dimers formed upon scf", "dimers formed upon scf binding", "upon scf binding allowing", "scf binding allowing these", "binding allowing these mutations", "allowing these mutations to support", "these mutations to support constitutive", "mutations to support constitutive activation", "to support constitutive activation of", "support constitutive activation of the", "constitutive activation of the receptor", "of the receptor yuzawa", "the receptor yuzawa et", "receptor yuzawa et al", "yuzawa et al 2007", "al 2007 reviewed", "2007 reviewed in lennartsson", "reviewed in lennartsson and ronnstrand", "lennartsson and ronnstrand 2012" ] }, { "record_id": "GLY_000594_1_2035", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9682706", "r hsa", "hsa 9682706", "r hsa 9682706" ] }, { "record_id": "GLY_000594_1_2035", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "replication of", "of the", "the sars", "sars cov", "cov 1", "1 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"of the rtc.", "the rtc. nsp14", "rtc. nsp14 also", "nsp14 also has", "also has the", "has the rna", "the rna capping", "rna capping activity", "capping activity and", "and in", "in concert with", "concert with nsp16", "nsp16 it", "it caps viral", "caps viral plus", "viral plus strand", "plus strand and", "strand and minus", "and minus strand", "minus strand genomic", "strand genomic and", "genomic and subgenomic", "and subgenomic rnas", "rnas which", "which confers stability", "confers stability to", "stability to viral", "to viral rnas", "viral rnas by", "rnas by enabling", "by enabling them", "enabling them to", "them to escape", "to escape interferon", "escape interferon mediated", "interferon mediated innate", "mediated innate immune", "innate immune responses", "immune responses of", "responses of the", "of the host.", "the host. nsp13", "host. nsp13 is", "nsp13 is an", "is an rna", "an rna helicase", "rna helicase which", "helicase which is", "which is thought", "thought to 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please", "please refer to", "refer to yang", "to yang and", "yang and leibowitz", "and leibowitz 2015", "2015 snijder", "snijder et al.", "et al. 2016", "2016 fung", "fung and liu", "and liu 2019.", "the plus strand rna", "plus strand rna genome", "strand rna genome of", "rna genome of the", "genome of the human", "of the human sars", "the human sars coronavirus", "human sars coronavirus 1", "coronavirus 1 sars", "1 sars cov", "cov 1 is", "1 is replicated", "is replicated by the", "replicated by the viral", "by the viral replication", "the viral replication transcription", "viral replication transcription complex", "transcription complex rtc", "rtc composed of", "composed of nonstructural proteins", "of nonstructural proteins nsp3", "nonstructural proteins nsp3 nsp16", "nsp3 nsp16 encoded", "nsp16 encoded by", "encoded by open reading", "by open reading frames", "open reading frames orf1a", "reading frames orf1a and", "frames orf1a and orf1b.", "orf1a and orf1b. two", "and orf1b. two 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rna", "has the rna capping", "the rna capping activity", "rna capping activity and", "activity and in", "and in concert", "in concert with nsp16", "with nsp16 it", "nsp16 it caps", "it caps viral plus", "caps viral plus strand", "viral plus strand and", "plus strand and minus", "strand and minus strand", "and minus strand genomic", "minus strand genomic and", "strand genomic and subgenomic", "genomic and subgenomic rnas", "subgenomic rnas which", "rnas which confers", "which confers stability to", "confers stability to viral", "stability to viral rnas", "to viral rnas by", "viral rnas by enabling", "rnas by enabling them", "by enabling them to", "enabling them to escape", "them to escape interferon", "to escape interferon mediated", "escape interferon mediated innate", "interferon mediated innate immune", "mediated innate immune responses", "innate immune responses of", "immune responses of the", "responses of the host.", "of the host. nsp13", "the host. nsp13 is", "host. nsp13 is an", 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"rna dependent rna polymerase activity.", "dependent rna polymerase activity. nsp12", "rna polymerase activity. nsp12 is", "polymerase activity. nsp12 is the", "activity. nsp12 is the main", "nsp12 is the main rna", "is the main rna polymerase", "main rna polymerase while", "rna polymerase while nsp8", "polymerase while nsp8 is", "while nsp8 is thought to", "nsp8 is thought to act", "is thought to act as", "thought to act as an", "to act as an rna", "act as an rna primase.", "as an rna primase. nsp14", "an rna primase. nsp14 acts", "rna primase. nsp14 acts as", "primase. nsp14 acts as a", "nsp14 acts as a 3'", "acts as a 3' 5'", "as a 3' 5' exonuclease", "3' 5' exonuclease increasing", "5' exonuclease increasing the", "exonuclease increasing the fidelity", "increasing the fidelity of the", "the fidelity of the rtc.", "fidelity of the rtc. nsp14", "of the rtc. nsp14 also", "the rtc. nsp14 also has", "rtc. nsp14 also has the", "nsp14 also has the rna", "also has the rna capping", "has the rna capping activity", "the rna capping activity and", "capping activity and in", "activity and in concert", "and in concert with", "concert with nsp16 it", "with nsp16 it caps", "nsp16 it caps viral", "it caps viral plus strand", "caps viral plus strand and", "viral plus strand and minus", "plus strand and minus strand", "strand and minus strand genomic", "and minus strand genomic and", "minus strand genomic and subgenomic", "strand genomic and subgenomic rnas", "and subgenomic rnas which", "subgenomic rnas which confers", "rnas which confers stability", "which confers stability to viral", "confers stability to viral rnas", "stability to viral rnas by", "to viral rnas by enabling", "viral rnas by enabling them", "rnas by enabling them to", "by enabling them to escape", "enabling them to escape interferon", "them to escape interferon mediated", "to escape interferon mediated innate", "escape interferon mediated innate immune", "interferon mediated innate immune responses", "mediated innate immune responses of", "innate immune responses of the", "immune responses of the host.", "responses of the host. nsp13", "of the host. nsp13 is", "the host. nsp13 is an", "host. nsp13 is an rna", "nsp13 is an rna helicase", "is an rna helicase which", "an rna helicase which is", "rna helicase which is thought", "helicase which is thought to", "which is thought to melt", "is thought to melt secondary", "thought to melt secondary structures", "to melt secondary structures in", "melt secondary structures in the", "secondary structures in the genomic", "structures in the genomic rna", "in the genomic rna during", "the genomic rna during replication", "genomic rna during replication and", "rna during replication and transcription.", "during replication and transcription. the", "replication and transcription. the plus", "and transcription. the plus strand", "transcription. the plus strand genomic", "the plus strand genomic rna", "plus strand genomic rna is", "strand genomic 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virions. for review", "virions. for review please", "for review please refer", "review please refer to", "please refer to yang and", "refer to yang and leibowitz", "to yang and leibowitz 2015", "and leibowitz 2015 snijder", "leibowitz 2015 snijder et", "2015 snijder et al.", "et al. 2016 fung", "al. 2016 fung and", "2016 fung and liu" ] }, { "record_id": "GLY_000594_1_2036", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9683673", "r hsa", "hsa 9683673", "r hsa 9683673" ] }, { "record_id": "GLY_000594_1_2036", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "maturation of", "of protein", "protein 3a", "maturation of protein", "of protein 3a", "maturation of protein 3a", "3a is", "is associated", "associated with", "with protein", "protein m", "m and", "and is", "is found", "found in", "in the", "the virion", "although its", "its function", "function in", "the structure", "structure seems", 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"heaphy et al.", "et al. 2011", "2011 gocha", "gocha et al.", "et al. 2014", "2014 pickett", "pickett and reddel", "and reddel 2015", "2015 amorim", "amorim et al.", "et al. 2016.", "many tumors that are", "tumors that are positive", "that are positive for", "are positive for markers", "positive for markers of", "for markers of alternative", "markers of alternative lengthening", "of alternative lengthening of", "alternative lengthening of telomeres", "of telomeres alt", "alt harbor loss", "harbor loss of function", "loss of function mutations", "of function mutations in", "function mutations in the", "mutations in the atrx", "in the atrx gene", "atrx gene encoding", "gene encoding a", "encoding a chromatin remodeling", "a chromatin remodeling protein", "chromatin remodeling protein atrx.", "remodeling protein atrx. atrx", "protein atrx. atrx is", "atrx. atrx is thought", "atrx is thought to", "is thought to act", "thought to act together", "to act together with", "act together with 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"the golgi the virion", "golgi the virion budding", "virion budding site li", "budding site li et", "site li et al", "li et al 2005", "al 2005 surjit", "2005 surjit et al", "surjit et al 2005", "et al 2005 ." ] }, { "record_id": "GLY_000594_1_2045", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717264", "r hsa", "hsa 9717264", "r hsa 9717264" ] }, { "record_id": "GLY_000594_1_2045", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "asp 3026", "3026 resistant", "resistant alk", "alk mutants", "asp 3026 resistant", "3026 resistant alk", "resistant alk mutants", "asp 3026 resistant alk", "3026 resistant alk mutants", "asp 3026 resistant alk mutants", "asp3026 is", "is a", "a second", "second generation", "generation tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor with", "with activity", "activity against", "against alk", "alk fusions", "fusions in", "in non", "non small", "small cell", "cell lung", "lung cancers", "and anaplastic", "anaplastic large", "large cell", "cell lymphomas", "alcls .", ". this", "this pathway", "pathway describes", "describes alk", "mutants that", "that are", "are resistant", "resistant to", "to inhibition", "inhibition by", "by asp3026", "amin et", "et al", "katayama et", "george et", "mori et", "reviewed roskoski", "lovly and", "and pao", "asp3026 is a", "is a second", "a second generation", "second generation tyrosine", "generation tyrosine kinase", "tyrosine kinase inhibitor", "kinase inhibitor with", "inhibitor with activity", "with activity against", "activity against alk", "against alk fusions", "alk fusions in", "fusions in non", "in non small", "non small cell", "small cell lung", "cell lung cancers", "cancers nsclc", "nsclc and", "and anaplastic large", "anaplastic large cell", "large cell lymphomas", "lymphomas alcls", "alcls . this", ". this pathway", "this pathway describes", "pathway describes alk", "describes alk mutants", "alk mutants that", "mutants that are", "that are resistant", "are resistant to", "resistant to inhibition", "to inhibition by", "inhibition by asp3026", "asp3026 amin", "amin et al", "al 2016", "2016 katayama", "katayama et al", "al 2014", "2014 george", "george et al", "al 2008", "2008 mori", "mori et al", "2014 reviewed", "roskoski 2013", "2013 lovly", "lovly and pao", "pao 2012", "asp3026 is a second", "is a second generation", "a second generation tyrosine", "second generation tyrosine kinase", "generation tyrosine kinase inhibitor", "tyrosine kinase inhibitor with", "kinase inhibitor with activity", "inhibitor with activity against", "with activity against alk", "activity against alk fusions", "against alk fusions in", "alk fusions in non", "fusions in non small", "in non small cell", "non small cell lung", "small cell lung cancers", "lung cancers nsclc", "nsclc and anaplastic", "and anaplastic large cell", "anaplastic large cell lymphomas", "cell lymphomas alcls", "lymphomas alcls .", "alcls . this pathway", ". this pathway describes", "this pathway describes alk", "pathway describes alk mutants", "describes alk mutants that", "alk mutants that are", "mutants that are resistant", "that are resistant to", "are resistant to inhibition", "resistant to inhibition by", "to inhibition by asp3026", "by asp3026 amin", "asp3026 amin et", "et al 2016", "2016 katayama et", "et al 2014", "2014 george et", "et al 2008", "2008 mori et", "2014 reviewed roskoski", "reviewed roskoski 2013", "2013 lovly and", "and pao 2012", "asp3026 is a second generation", "is a second generation tyrosine", "a second generation tyrosine kinase", "second generation tyrosine kinase inhibitor", "generation tyrosine kinase inhibitor with", "tyrosine kinase inhibitor with activity", "kinase inhibitor with activity against", "inhibitor with activity against alk", "with activity against alk fusions", "activity against alk fusions in", "against alk fusions in non", "alk fusions in non small", "fusions in non small cell", "in non small cell lung", "non small cell lung cancers", "cell lung cancers nsclc", "cancers nsclc and", "nsclc and anaplastic large", "and anaplastic large cell lymphomas", "large cell lymphomas alcls", "cell lymphomas alcls .", "lymphomas alcls . this", "alcls . this pathway describes", ". this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to inhibition", "are resistant to inhibition by", "resistant to inhibition by asp3026", "inhibition by asp3026 amin", "by asp3026 amin et", "asp3026 amin et al", "amin et al 2016", "al 2016 katayama", "2016 katayama et al", "katayama et al 2014", "al 2014 george", "2014 george et al", "george et al 2008", "al 2008 mori", "2008 mori et al", "mori et al 2014", "al 2014 reviewed", "roskoski 2013 lovly", "2013 lovly and pao", "lovly and pao 2012" ] }, { "record_id": "GLY_000594_1_2046", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717301", "r hsa", "hsa 9717301", "r hsa 9717301" ] }, { "record_id": "GLY_000594_1_2046", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nvp tae684", "tae684 resistant", "resistant alk", "alk mutants", "nvp tae684 resistant", "tae684 resistant alk", "resistant alk mutants", "nvp tae684 resistant alk", "tae684 resistant alk mutants", "nvp tae684 resistant alk mutants", "tae684 is", "is a", "a second", "second generation", "generation tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor with", "with activity", "activity against", "against some", "some alk", "including some", "some that", "that show", "show resistance", "resistance to", "to crizotinib", "george et", "et al", "sasaki et", "heuckmann et", "ceccon et", "2013 .", ". this", "this pathway", "pathway describes", "describes alk", "mutants that", "to inhibition", "inhibition by", "by nvp", "nvp tae684.", "nvp tae684 is", "tae684 is a", "is a second", "a second generation", "second generation tyrosine", "generation tyrosine kinase", "tyrosine kinase inhibitor", "kinase inhibitor with", "inhibitor with activity", "with activity against", "activity against some", "against some alk", "some alk mutants", "mutants including", "including some that", "some that show", "that show resistance", "show resistance to", "resistance to crizotinib", "crizotinib george", "george et al", "al 2008", "2008 sasaki", "sasaki et al", "al 2011", "2011 heuckmann", "heuckmann et al", "2011 ceccon", "ceccon et al", "al 2013", "2013 . this", ". this pathway", "this pathway describes", "pathway describes alk", "describes alk mutants", "alk mutants that", "mutants that show", "resistance to inhibition", "to inhibition by", "inhibition by nvp", "by nvp tae684.", "nvp tae684 is a", "tae684 is a second", "is a second generation", "a second generation tyrosine", "second generation tyrosine kinase", "generation tyrosine kinase inhibitor", "tyrosine kinase inhibitor with", "kinase inhibitor with activity", "inhibitor with activity against", "with activity against some", "activity against some alk", "against some alk mutants", "alk mutants including", "mutants including some", "including some that show", "some that show resistance", "that show resistance to", "show resistance to crizotinib", "to crizotinib george", "crizotinib george et", "et al 2008", "2008 sasaki et", "et al 2011", "2011 heuckmann et", "2011 ceccon et", "et al 2013", "al 2013 .", "2013 . this pathway", ". this pathway describes", "this pathway describes alk", "pathway describes alk mutants", "describes alk mutants that", "alk mutants that show", "mutants that show resistance", "show resistance to inhibition", "resistance to inhibition by", "to inhibition by nvp", "inhibition by nvp tae684.", "nvp tae684 is a second", "tae684 is a second generation", "is a second generation tyrosine", "a second generation tyrosine kinase", "second generation tyrosine kinase inhibitor", "generation tyrosine kinase inhibitor with", "tyrosine kinase inhibitor with activity", "kinase inhibitor with activity against", "inhibitor with activity against some", "with activity against some alk", "activity against some alk mutants", "some alk mutants including", "alk mutants including some", "mutants including some that", "including some that show resistance", "some that show resistance to", "that show resistance to crizotinib", "resistance to crizotinib george", "to crizotinib george et", "crizotinib george et al", "george et al 2008", "al 2008 sasaki", "2008 sasaki et al", "sasaki et al 2011", "al 2011 heuckmann", "2011 heuckmann et al", "heuckmann et al 2011", "al 2011 ceccon", "2011 ceccon et al", "ceccon et al 2013", "et al 2013 .", "al 2013 . this", "2013 . this pathway describes", ". this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that show", "alk mutants that show resistance", "mutants that show resistance to", "that show resistance to inhibition", "show resistance to inhibition by", "resistance to inhibition by nvp", "to inhibition by nvp tae684." ] }, { "record_id": "GLY_000594_1_2047", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717316", "r hsa", "hsa 9717316", "r hsa 9717316" ] }, { "record_id": "GLY_000594_1_2047", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "alectinib resistant", "resistant alk", "alk mutants", "alectinib resistant alk", "resistant alk mutants", "alectinib resistant alk mutants", "alectinib is", "is a", "a second", "second generation", "generation tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor that", "that is", "is approved", "approved for", "for use", "use in", "in alk", "alk positive", "positive non", "non small", "small cell", "cell lung", "lung cancers", "nsclcs .", ". alectinib", "is effective", "effective against", "against a", "a number", "number of", "of alk", "mutants that", "that arise", "arise after", "after treatment", "treatment with", "with crizotinib", "however resistance", "resistance to", "to alectinib", "alectinib has", "has also", "also been", "been reported.", "reported. this", "this pathway", "pathway describes", "describes alk", "that are", "are resistant", "resistant to", "to inhibition", "inhibition with", "with alectinib", "reviewed in", "in lovly", "lovly and", "and pao", "lin et", "et al", "della corte", "corte et", "hallberg and", "and palmer", "2016 .", "alectinib is a", "is a second", "a second generation", "second generation tyrosine", "generation tyrosine kinase", "tyrosine kinase inhibitor", "kinase inhibitor that", "inhibitor that is", "that is approved", "is approved for", "approved for use", "for use in", "use in alk", "in alk positive", "alk positive non", "positive non small", "non small cell", "small cell lung", "cell lung cancers", "cancers nsclcs", "nsclcs . alectinib", ". alectinib is", "alectinib is effective", "is effective against", "effective against a", "against a number", "a number of", "number of alk", "of alk mutants", "alk mutants that", "mutants that arise", "that arise after", "arise after treatment", "after treatment with", "treatment with crizotinib", "crizotinib however", "however resistance to", "resistance to alectinib", "to alectinib has", "alectinib has also", "has also been", "also been reported.", "been reported. this", "reported. this pathway", "this pathway describes", "pathway describes alk", "describes alk mutants", "mutants that are", "that are resistant", "are resistant to", "resistant to inhibition", "to inhibition with", "inhibition with alectinib", "alectinib reviewed", "reviewed in lovly", "in lovly and", "lovly and pao", "pao 2012", "2012 lin", "lin et al", "al 2017", "2017 della", "della corte et", "corte et al", "al 2018", "2018 hallberg", "hallberg and palmer", "palmer 2016", "alectinib is a second", "is a second generation", "a second generation tyrosine", "second generation tyrosine kinase", "generation tyrosine kinase inhibitor", "tyrosine kinase inhibitor that", "kinase inhibitor that is", "inhibitor that is approved", "that is approved for", "is approved for use", "approved for use in", "for use in alk", "use in alk positive", "in alk positive non", "alk positive non small", "positive non small cell", "non small cell lung", "small cell lung cancers", "lung cancers nsclcs", "cancers nsclcs .", "nsclcs . alectinib is", ". alectinib is effective", "alectinib is effective against", "is effective against a", "effective against a number", "against a number of", "a number of alk", "number of alk mutants", "of alk mutants that", "alk mutants that arise", "mutants that arise after", "that arise after treatment", "arise after treatment with", "after treatment with crizotinib", "with crizotinib however", "crizotinib however resistance", "however resistance to alectinib", "resistance to alectinib has", "to alectinib has also", "alectinib has also been", "has also been reported.", "also been reported. this", "been reported. this pathway", "reported. this pathway describes", "this pathway describes alk", "pathway describes alk mutants", "describes alk mutants that", "alk mutants that are", "mutants that are resistant", "that are resistant to", "are resistant to inhibition", "resistant to inhibition with", "to inhibition with alectinib", "with alectinib reviewed", "alectinib reviewed in", "reviewed in lovly and", "in lovly and pao", "and pao 2012", "2012 lin et", "et al 2017", "2017 della corte", "della corte et al", "et al 2018", "2018 hallberg and", "and palmer 2016", "palmer 2016 .", "alectinib is a second generation", "is a second generation tyrosine", "a second generation tyrosine kinase", "second generation tyrosine kinase inhibitor", "generation tyrosine kinase inhibitor that", "tyrosine kinase inhibitor that is", "kinase inhibitor that is approved", "inhibitor that is approved for", "that is approved for use", "is approved for use in", "approved for use in alk", "for use in alk positive", "use in alk positive non", "in alk positive non small", "alk positive non small cell", "positive non small cell lung", "non small cell lung cancers", "cell lung cancers nsclcs", "lung cancers nsclcs .", "cancers nsclcs . alectinib", "nsclcs . alectinib is effective", ". alectinib is effective against", "alectinib is effective against a", "is effective against a number", "effective against a number of", "against a number of alk", "a number of alk mutants", "number of alk mutants that", "of alk mutants that arise", "alk mutants that arise after", "mutants that arise after treatment", "that arise after treatment with", "arise after treatment with crizotinib", "treatment with crizotinib however", "with crizotinib however resistance", "crizotinib however resistance to", "however resistance to alectinib has", "resistance to alectinib has also", "to alectinib has also been", "alectinib has also been reported.", "has also been reported. this", "also been reported. this pathway", "been reported. this pathway describes", "reported. this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to inhibition", "are resistant to inhibition with", "resistant to inhibition with alectinib", "inhibition with alectinib reviewed", "with alectinib reviewed in", "alectinib reviewed in lovly", "reviewed in lovly and pao", "lovly and pao 2012", "pao 2012 lin", "2012 lin et al", "lin et al 2017", "al 2017 della", "2017 della corte et", "corte et al 2018", "al 2018 hallberg", "2018 hallberg and palmer", "hallberg and palmer 2016", "and palmer 2016 ." ] }, { "record_id": "GLY_000594_1_2048", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717319", "r hsa", "hsa 9717319", "r hsa 9717319" ] }, { "record_id": "GLY_000594_1_2048", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "brigatinib resistant", "resistant alk", "alk mutants", "brigatinib resistant alk", "resistant alk mutants", "brigatinib resistant alk mutants", "brigatinib is", "is a", "a second", "second generation", "generation tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor with", "with activity", "activity against", "against alk.", "alk. this", "this pathway", "pathway describes", "describes alk", "mutants that", "that are", "are resistant", "resistant to", "to inhibition", "inhibition by", "by brigatinib", "reviewed in", "in della", "della corte", "corte et", "et al", "lin and", "and pao", "hallberg and", "and palmer", "2013 .", "brigatinib is a", "is a second", "a second generation", "second generation 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this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to inhibition", "are resistant to inhibition by", "resistant to inhibition by brigatinib", "inhibition by brigatinib reviewed", "by brigatinib reviewed in", "brigatinib reviewed in della", "reviewed in della corte et", "in della corte et al", "corte et al 2018", "al 2018 roskoski", "2018 roskoski 2013", "roskoski 2013 lin", "2013 lin and pao", "lin and pao 2017", "pao 2017 hallberg", "2017 hallberg and palmer", "hallberg and palmer 2013", "and palmer 2013 ." ] }, { "record_id": "GLY_000594_1_2049", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717323", "r hsa", "hsa 9717323", "r hsa 9717323" ] }, { "record_id": "GLY_000594_1_2049", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ceritinib resistant", "resistant alk", "alk mutants", "ceritinib resistant alk", "resistant alk mutants", "ceritinib resistant alk mutants", "ceritinib is", "is a", "a type", "type i", "i tki", "tki that", "that is", "is effective", "effective against", "against alk", "alk driven", "driven cancers", "cancers and", "and is", "is approved", "approved for", "for treatment", "treatment of", "of nsclc.", "nsclc. ceritinib", "a second", "second generation", "generation tki", "that shows", "shows activity", "activity against", "against a", "a number", "number of", "of crizotinib", "crizotinib resistant", "alk alleles", "resistance to", "to ceritinib", "ceritinib has", "has also", "also been", "been documented.", "documented. this", "this pathway", "pathway describes", "describes alk", "mutants that", "that are", "are resistant", "resistant to", "to inhibition", "inhibition with", "with ceritinib", "reviewed in", "in lovly", "lovly and", "and pao", "lin et", "et al", "della corte", "corte et", "2018 .", "ceritinib is a", "is a type", "a type i", "type i tki", "i tki that", "tki that is", "that is effective", "is effective against", "effective against alk", "against alk driven", "alk driven cancers", "driven cancers and", "cancers and is", "and is approved", "is approved for", "approved for treatment", "for treatment of", "treatment of nsclc.", "of nsclc. ceritinib", "nsclc. ceritinib is", "is a second", "a second generation", "second generation tki", "generation tki that", "tki that shows", "that shows activity", "shows activity against", "activity against a", "against a number", "a number of", "number of crizotinib", "of crizotinib resistant", "crizotinib resistant alk", "resistant alk alleles", "alleles however", "however resistance", "resistance to ceritinib", "to ceritinib has", "ceritinib has also", "has also been", "also been documented.", "been documented. this", "documented. this pathway", "this pathway describes", "pathway describes alk", 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"al 2018 .", "ceritinib is a type i", "is a type i tki", "a type i tki that", "type i tki that is", "i tki that is effective", "tki that is effective against", "that is effective against alk", "is effective against alk driven", "effective against alk driven cancers", "against alk driven cancers and", "alk driven cancers and is", "driven cancers and is approved", "cancers and is approved for", "and is approved for treatment", "is approved for treatment of", "approved for treatment of nsclc.", "for treatment of nsclc. ceritinib", "treatment of nsclc. ceritinib is", "of nsclc. ceritinib is a", "nsclc. ceritinib is a second", "ceritinib is a second generation", "is a second generation tki", "a second generation tki that", "second generation tki that shows", "generation tki that shows activity", "tki that shows activity against", "that shows activity against a", "shows activity against a number", "activity against a number of", "against a number of crizotinib", "a number of crizotinib resistant", "number of crizotinib resistant alk", "of crizotinib resistant alk alleles", "resistant alk alleles however", "alleles however resistance", "however resistance to ceritinib", "resistance to ceritinib has also", "to ceritinib has also been", "ceritinib has also been documented.", "has also been documented. this", "also been documented. this pathway", "been documented. this pathway describes", "documented. this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to inhibition", "are resistant to inhibition with", "resistant to inhibition with ceritinib", "inhibition with ceritinib reviewed", "with ceritinib reviewed in", "ceritinib reviewed in lovly", "reviewed in lovly and pao", "lovly and pao 2012", "pao 2012 lin", "2012 lin et al", "lin et al 2017", "al 2017 della", "2017 della corte et", "corte et al 2018", "et al 2018 ." ] }, { "record_id": "GLY_000594_1_2050", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717326", "r hsa", "hsa 9717326", "r hsa 9717326" ] }, { "record_id": "GLY_000594_1_2050", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "crizotinib resistant", "resistant alk", "alk mutants", "crizotinib resistant alk", "resistant alk mutants", "crizotinib resistant alk mutants", "crizotinib is", "is a", "a type", "type i", "i tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor that", "that is", "is approved", "approved for", "for treatment", "treatment of", "of alk", "alk positive", "positive non", "non small", "small cell", "cell lung", "lung cancer.", "cancer. crizotinib", "is also", "also effective", "effective against", "against alcl", "alcl and", "and imts.", "imts. development", "development of", "of resistance", "resistance to", "to crizotinib", "is not", "not uncommon", "with patients", "patients acquiring", "acquiring secondary", "secondary mutations", "mutations or", "or amplifications", "amplifications of", "of the", "the alk", "alk gene", "gene that", "that limit", "limit the", "the effectiveness", "effectiveness of", "the drug.", "drug. this", "this pathway", "pathway describes", "describes alk", "mutants that", "that are", "are resistant", "resistant to", "crizotinib mediated", "mediated inhibition", "reviewed in", "in roskoski", "lin et", "et al", "della corte", "corte et", "2018 .", "crizotinib is a", "is a type", "a type i", "type i tyrosine", "i tyrosine kinase", "tyrosine kinase inhibitor", "kinase inhibitor that", "inhibitor that is", "that is approved", "is approved for", "approved for treatment", "for treatment of", "treatment of alk", "of alk positive", "alk positive non", "positive non small", "non small cell", "small cell lung", "cell lung cancer.", "lung cancer. crizotinib", "cancer. crizotinib is", "crizotinib is also", "is also effective", "also effective against", "effective against alcl", "against alcl and", "alcl and imts.", "and imts. development", "imts. development of", "development of resistance", "of resistance to", "resistance to crizotinib", "to crizotinib is", "crizotinib is not", "is not uncommon", "uncommon however", "however with", "with patients acquiring", "patients acquiring secondary", "acquiring secondary mutations", "secondary mutations or", "mutations or amplifications", "or amplifications of", "amplifications of the", "of the alk", "the alk gene", "alk gene that", "gene that limit", "that limit the", "limit the effectiveness", "the effectiveness of", "effectiveness of the", "of the drug.", "the drug. this", "drug. this pathway", "this pathway describes", "pathway describes alk", "describes alk mutants", "alk mutants that", "mutants that are", "that are resistant", "are resistant to", "resistant to crizotinib", "to crizotinib mediated", "crizotinib mediated inhibition", "inhibition reviewed", "reviewed in roskoski", "roskoski 2013", "2013 lin", "lin et al", "al 2017", "2017 della", "della corte et", "corte et al", "al 2018", "crizotinib is a type", "is a type i", "a type i tyrosine", "type i tyrosine kinase", "i tyrosine kinase inhibitor", "tyrosine kinase inhibitor that", "kinase inhibitor that is", "inhibitor that is approved", "that is approved for", "is approved for treatment", "approved for treatment of", "for treatment of alk", "treatment of alk positive", "of alk positive non", "alk positive non small", "positive non small cell", "non small cell lung", "small cell lung cancer.", "cell lung cancer. crizotinib", "lung cancer. crizotinib is", "cancer. crizotinib is also", "crizotinib is also effective", "is also effective against", "also effective against alcl", "effective against alcl and", "against alcl and imts.", "alcl and imts. development", "and imts. development of", "imts. development of resistance", "development of resistance to", "of resistance to crizotinib", "resistance to crizotinib is", "to crizotinib is not", "crizotinib is not uncommon", "not uncommon however", "however with patients", "with patients acquiring secondary", "patients acquiring secondary mutations", "acquiring secondary mutations or", "secondary mutations or amplifications", "mutations or amplifications of", "or amplifications of the", "amplifications of the alk", "of the alk gene", "the alk gene that", "alk gene that limit", "gene that limit the", "that limit the effectiveness", "limit the effectiveness of", "the effectiveness of the", "effectiveness of the drug.", "of the drug. this", "the drug. this pathway", "drug. this pathway describes", "this pathway describes alk", "pathway describes alk mutants", "describes alk mutants that", "alk mutants that are", "mutants that are resistant", "that are resistant to", "are resistant to crizotinib", "resistant to crizotinib mediated", "to crizotinib mediated inhibition", "mediated inhibition reviewed", "inhibition reviewed in", "in roskoski 2013", "2013 lin et", "et al 2017", "2017 della corte", "della corte et al", "et al 2018", "al 2018 .", "crizotinib is a type i", "is a type i tyrosine", "a type i tyrosine kinase", "type i tyrosine kinase inhibitor", "i tyrosine kinase inhibitor that", "tyrosine kinase inhibitor that is", "kinase inhibitor that is approved", "inhibitor that is approved for", "that is approved for treatment", "is approved for treatment of", "approved for treatment of alk", "for treatment of alk positive", "treatment of alk positive non", "of alk positive non small", "alk positive non small cell", "positive non small cell lung", "non small cell lung cancer.", "small cell lung cancer. crizotinib", "cell lung cancer. crizotinib is", "lung cancer. crizotinib is also", "cancer. crizotinib is also effective", "crizotinib is also effective against", "is also effective against alcl", "also effective against alcl and", "effective against alcl and imts.", "against alcl and imts. development", "alcl and imts. development of", "and imts. development of resistance", "imts. development of resistance to", "development of resistance to crizotinib", "of resistance to crizotinib is", "resistance to crizotinib is not", "to crizotinib is not uncommon", "is not uncommon however", "uncommon however with", "however with patients acquiring", "with patients acquiring secondary mutations", "patients acquiring secondary mutations or", "acquiring secondary mutations or amplifications", "secondary mutations or amplifications of", "mutations or amplifications of the", "or amplifications of the alk", "amplifications of the alk gene", "of the alk gene that", "the alk gene that limit", "alk gene that limit the", "gene that limit the effectiveness", "that limit the effectiveness of", "limit the effectiveness of the", "the effectiveness of the drug.", "effectiveness of the drug. this", "of the drug. this pathway", "the drug. this pathway describes", "drug. this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to crizotinib", "are resistant to crizotinib mediated", "resistant to crizotinib mediated inhibition", "crizotinib mediated inhibition reviewed", "mediated inhibition reviewed in", "inhibition reviewed in roskoski", "reviewed in roskoski 2013", "roskoski 2013 lin", "2013 lin et al", "lin et al 2017", "al 2017 della", "2017 della corte et", "corte et al 2018", "et al 2018 ." ] }, { "record_id": "GLY_000594_1_2051", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9717329", "r hsa", "hsa 9717329", "r hsa 9717329" ] }, { "record_id": "GLY_000594_1_2051", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "lorlatinib resistant", "resistant alk", "alk mutants", "lorlatinib resistant alk", "resistant alk mutants", "lorlatinib resistant alk mutants", "lorlatinib is", "is a", "a third", "third generation", "generation tyrosine", "tyrosine kinase", "kinase inhibitor", "inhibitor with", "with effectiveness", "effectiveness against", "against alk", "alk and", "and ros", "ros rearranged", "rearranged cancers.", "cancers. this", "this pathway", "pathway describes", "describes alk", "mutants that", "that are", "are resistant", "resistant to", "to inhibition", "inhibition by", "by lorlatinib", "yoda et", "et al", "takahashi et", "reviewed in", "in della", "della corte", "corte et", "lin et", "facchinietti et", "2016 .", "lorlatinib is a", "is a third", "a third generation", "third generation tyrosine", "generation tyrosine kinase", "tyrosine kinase inhibitor", "kinase inhibitor with", "inhibitor with effectiveness", "with effectiveness against", "effectiveness against alk", "against alk and", "alk and ros", "and ros rearranged", "ros rearranged cancers.", "rearranged cancers. this", "cancers. this pathway", "this pathway describes", "pathway describes alk", "describes alk mutants", "alk mutants that", "mutants that are", "that are resistant", "are resistant to", "resistant to inhibition", "to inhibition by", "inhibition by lorlatinib", "lorlatinib yoda", "yoda et al", "al 2018", "2018 takahashi", "takahashi et al", "al 2020", "2020 reviewed", "reviewed in della", "in della corte", "della corte et", "corte et al", "2018 lin", "lin et al", "al 2017", "2017 facchinietti", "facchinietti et al", "al 2016", "lorlatinib is a third", "is a third generation", "a third generation tyrosine", "third generation tyrosine kinase", "generation tyrosine kinase inhibitor", "tyrosine kinase inhibitor with", "kinase inhibitor with effectiveness", "inhibitor with effectiveness against", "with effectiveness against alk", "effectiveness against alk and", "against alk and ros", "alk and ros rearranged", "and ros rearranged cancers.", "ros rearranged cancers. this", "rearranged cancers. this pathway", "cancers. this pathway describes", "this pathway describes alk", "pathway describes alk mutants", "describes alk mutants that", "alk mutants that are", "mutants that are resistant", "that are resistant to", "are resistant to inhibition", "resistant to inhibition by", "to inhibition by lorlatinib", "by lorlatinib yoda", "lorlatinib yoda et", "et al 2018", "2018 takahashi et", "et al 2020", "2020 reviewed in", "reviewed in della corte", "in della corte et", "della corte et al", "2018 lin et", "et al 2017", "2017 facchinietti et", "et al 2016", "al 2016 .", "lorlatinib is a third generation", "is a third generation tyrosine", "a third generation tyrosine kinase", "third generation tyrosine kinase inhibitor", "generation tyrosine kinase inhibitor with", "tyrosine kinase inhibitor with effectiveness", "kinase inhibitor with effectiveness against", "inhibitor with effectiveness against alk", "with effectiveness against alk and", "effectiveness against alk and ros", "against alk and ros rearranged", "alk and ros rearranged cancers.", "and ros rearranged cancers. this", "ros rearranged cancers. this pathway", "rearranged cancers. this pathway describes", "cancers. this pathway describes alk", "this pathway describes alk mutants", "pathway describes alk mutants that", "describes alk mutants that are", "alk mutants that are resistant", "mutants that are resistant to", "that are resistant to inhibition", "are resistant to inhibition by", "resistant to inhibition by lorlatinib", "inhibition by lorlatinib yoda", "by lorlatinib yoda et", "lorlatinib yoda et al", "yoda et al 2018", "al 2018 takahashi", "2018 takahashi et al", "takahashi et al 2020", "al 2020 reviewed", "2020 reviewed in della", "reviewed in della corte et", "in della corte et al", "corte et al 2018", "al 2018 lin", "2018 lin et al", "lin et al 2017", "al 2017 facchinietti", "2017 facchinietti et al", "facchinietti et al 2016", "et al 2016 ." ] }, { "record_id": "GLY_000594_1_2052", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9772755", "r hsa", "hsa 9772755", "r hsa 9772755" ] }, { "record_id": "GLY_000594_1_2052", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of wdr5", "wdr5 containing", "containing histone", "histone modifying", "modifying complexes", "formation of wdr5", "of wdr5 containing", "wdr5 containing histone", "containing histone modifying", "histone modifying complexes", "formation of wdr5 containing", "of wdr5 containing histone", "wdr5 containing histone modifying", "containing histone modifying complexes", "formation of wdr5 containing histone", "of wdr5 containing histone modifying", "wdr5 containing histone modifying complexes", "wdr5 is", "is a", "a component", "component of", "of six", "six mammalian", "mammalian histone", "histone methyltransferase", "methyltransferase kmt2", "kmt2 complexes:", "complexes: mixed", "mixed lineage", "lineage leukemia", "1 4", "and set1b.", "set1b. all", "all kmt2", "kmt2 complexes", "complexes consist", "consist of", "of a", "a histone", "or setd1b", "and the", "the wrad", "wrad subcomplex", "subcomplex composed", "composed of", "and dpy30.", "dpy30. the", "wrad complex", "complex regulates", "regulates the", "the enzymatic", "enzymatic activity", "activity of", "of histone", "histone methyltransferases", "methyltransferases and", "and enables", "enables their", "their recruitment", "recruitment to", "to chromatin.", "chromatin. additional", "additional transcription", "transcription cofactors", "cofactors associate", "associate with", "with each", "each kmt2", "kmt2 histone", "methyltransferase complex", "enabling their", "their functional", "functional diversification.", "diversification. for", "for a", "a detailed", "detailed overview", "please refer", "refer to", "to cho", "cho et", "et al.", "al. 2007", "song and", "and kingston", "kingston 2008", "takahashi et", "al. 2011", "couture and", "and skiniotis", "skiniotis 2013", "van nuland", "nuland et", "al. 2013", "klonou et", "al. 2021.

              the", "2021.

              the kmt2", "complexes are", "are evolutionarily", "evolutionarily conserved.", "conserved. while", "while a", "a single", "single set1/compass", "set1/compass complex", "complex is", "is present", "present in", "in yeast", "three distinct", "distinct complexes", "are present", "in drosophila:", "drosophila: trithorax", "trithorax related", "and set1.", "set1. in", "in mammals", "due to", "to gene", "gene duplication", "two trx", "trx like", "like complexes", "one with", "with kmt2a", "kmt2a and", "and another", "another with", "with kmt2b", "kmt2b as", "as the", "the catalytic", "catalytic subunit", "as well", "well as", "as two", "two trr", "trr like", "with kmt2c", "kmt2c and", "with kmt2d", "kmt2d as", "and two", "two set1", "set1 like", "with setd1a", "setd1a and", "with setd1b", "setd1b as", "are formed.", "formed. for", "for review", "to rao", "rao and", "and dou", "dou 2015.

              all", "2015.

              all kmt2", "complexes methylate", "methylate lysine", "lysine k5", "k5 of", "histone h3", "k4 in", "in mature", "mature histone", "h3 peptides", "the initiator", "initiator methionine", "methionine is", "is removed", "which is", "is associated", "associated with", "with transcriptional", "transcriptional activation.", "activation. different", "different kmt2", "complexes preferentially", "preferentially monomethylate", "or trimethylate", "trimethylate h3k4", "depending on", "on the", "the presence", "presence of", "of accessory", "accessory subunits", "transcriptional co", "co factors", "and posttranslational", "posttranslational modifications.", "modifications. the", "catalytic activity", "of kmt2", "complexes may", "may differ", "differ between", "between endogenous", "endogenous complexes", "complexes and", "and complexes", "complexes reconstituted", "reconstituted in", "in vitro", "vitro by", "by mammalian", "mammalian proteins", "proteins expressed", "expressed and", "and produced", "produced in", "in bacterial", "bacterial or", "or insect", "insect cells.", "cells. the", "the kmt2a", "and kmt2b", "kmt2b complexes", "preferentially methylate", "methylate h3k4", "h3k4 at", "at a", "a limited", "limited number", "number of", "of target", "target gene", "gene promoters", "while kmt2c", "and kmt2d", "kmt2d complexes", "gene enhancers.", "enhancers. setd1a", "and setd1b", "setd1b complexes", "are responsible", "responsible for", "for the", "the bulk", "bulk of", "of cellular", "cellular h3k4", "h3k4 methylation", "methylation and", "and show", "show less", "less target", "target specificity.", "specificity. for", "for overview", "to patel", "patel et", "al. 2009", "wang et", "dou 2015.

              in", "2015.

              in both", "both drosophila", "drosophila and", "and vertebrates", "complexes control", "control the", "the expression", "expression of", "of evolutionarily", "evolutionarily conserved", "conserved hox", "hox genes", "genes which", "which serve", "serve as", "as master", "master regulators", "regulators of", "of embryonic", "embryonic patterning", "reviewed in", "in soshnikova", "soshnikova and", "and duboule", "duboule 2009", "2009 .

              germline", ".

              germline mutations", "mutations in", "in human", "human kmt2", "are the", "the underlying", "underlying cause", "cause of", "of several", "several chromatinopathies.", "chromatinopathies. germline", "germline loss", "loss of", "of function", "in kmt2a", "kmt2a cause", "cause weideman", "weideman steiner", "steiner syndrome", "a rare", "rare autosomal", "autosomal dominant", "dominant disorder", "disorder characterized", "characterized by", "by intellectual", "intellectual disability", "developmental delay", "and post", "post natal", "natal growth", "growth delay", "short stature", "distinctive facial", "facial features", "skeletal abnormalities", "feeding problems", "problems and", "and behavioral", "behavioral difficulties", "in castiglioni", "castiglioni et", "al. 2022", "2022 .", ". germline", "germline lof", "lof mutations", "in kmt2b", "kmt2b cause", "cause dystonia", "dystonia 28", "and intellectual", "intellectual developmental", "disorder 68", "mrd68 .", ". dyt28", "dyt28 is", "is an", "an autosomal", "dominant neurologic", "neurologic disorder", "by onset", "onset of", "of progressive", "progressive dystonia", "dystonia in", "in the", "the first", "first decade", "decade of", "of life", "in zech", "zech et", "al. 2019", "while mrd68", "mrd68 is", "by developmental", "developmental delay/intellectual", "delay/intellectual disability", "poor growth", "feeding difficulties", "and dysmorphic", "dysmorphic features", "cif et", "al. 2020", "2020 .", "in kmt2c", "kmt2c cause", "cause kleefstra", "kleefstra syndrome", "syndrome 2", "dominant neurodevelopmental", "neurodevelopmental disorder", "by delayed", "delayed psychomotor", "psychomotor development", "variable intellectual", "and mild", "mild dysmorphic", "in lavery", "lavery et", "in kmt2d", "kmt2d cause", "cause kabuki", "kabuki syndrome", "syndrome 1", "a congenital", "congenital mental", "mental retardation", "retardation syndrome", "syndrome with", "with postnatal", "postnatal dwarfism", "a facial", "facial dysmorphism", "dysmorphism and", "and skeletal", "in setd1a", "setd1a cause", "cause early", "early onset", "onset epilepsy", "epilepsy with", "with or", "or without", "without developmental", "yu et", "and neurodevelopmental", "disorder with", "with speech", "speech impairment", "impairment and", "dysmorphic facies", "kummeling et", "al. 2021", "2021 .", "in setd1b", "setd1b cause", "cause intellectual", "developmental disorder", "with seizures", "seizures and", "and language", "language delay", "roston et", "2021 .

              somatic", ".

              somatic mutations", "in kmt2", "kmt2 genes", "genes contribute", "contribute to", "to cancer", "cancer development.", "development. they", "they were", "were first", "first discovered", "discovered in", "in mixed", "by chromosomal", "chromosomal translocations", "translocations that", "that involve", "involve the", "kmt2a gene", "gene locus", "locus on", "on chromosome", "chromosome 11", "chromosomal band", "band 11q23", "and result", "result in", "of fusion", "fusion proteins", "proteins with", "with oncogenic", "oncogenic properties.", "properties. besides", "besides gene", "gene fusions", "other types", "types of", "of kmt2a", "kmt2a mutations", "mutations are", "are also", "also present", "in blood", "blood cancers", "most frequently", "frequently in", "in high", "high grade", "grade b", "b cell", "cell lymphoma", "t cell", "cell lymphoblastic", "lymphoblastic leukemia", "and acute", "acute myeloid", "myeloid leukemia", "and solid", "solid tumors", "most often", "often reported", "reported in", "in lung", "lung adenocarcinoma", "colon adenocarcinoma", "and bladder", "bladder urothelial", "urothelial carcinoma", "carcinoma .", ". somatic", "somatic cancer", "cancer mutations", "in other", "other kmt2", "are less", "less characterized", "characterized but", "but most", "frequently affect", "affect the", "catalytic set", "set domain", "domain and", "show different", "different distributions", "distributions between", "between different", "different cancer", "cancer types.", "types. for", "dou 2015", "al. 2022.", "2022. several", "several anti", "anti cancer", "cancer therapeutics", "therapeutics are", "are being", "being developed", "developed that", "that affect", "the association", "association of", "kmt2 enzymes", "enzymes with", "with components", "components of", "of the", "in particular", "particular wdr5", "in vedadi", "vedadi et", "al. 2017", "siladi et", "2022 .

              wdr5", ".

              wdr5 is", "is also", "also a", "of three", "three histone", "histone acetyltransferase", "acetyltransferase complexes", "gcn5 atac", "pcaf atac", "and mof/kat8", "mof/kat8 nsl.", "nsl. the", "the role", "role of", "wdr5 in", "in epigenetic", "epigenetic regulation", "regulation of", "of gene", "gene expression", "expression through", "through histone", "histone acetylation", "acetylation is", "is under", "under investigation", "in guarnaccia", "guarnaccia and", "and tansey", "tansey 2018", "2018 .

              the", ".

              the function", "function of", "complexes is", "is currently", "currently depicted", "depicted in", "the following", "following reactome", "reactome pathways:", "pathways: \\transcriptional", "\\transcriptional regulation", "of granulopoiesis\\", "mll1 complex", "regulation by", "by runx1\\", "\\activation of", "of anterior", "anterior hox", "genes in", "in hindbrain", "hindbrain development", "development during", "during early", "early embryogenesis\\", "mll3 complex", "complex and", "and mll4", "mll4 complex", "\\tcf dependent", "dependent signaling", "signaling in", "in response", "response to", "to wnt\\", "and \\chromatin", "\\chromatin organization\\", "mll2 complex", "set1a complex", "set1b complex", "atac complex", "mof/kat8 nsl", "nsl complex", "complex .", ". please", "please note", "note that", "that there", "there is", "an inconsistency", "inconsistency in", "in naming", "naming of", "of mll2", "mll2 and", "mll4 complexes", "complexes in", "the literature", "literature and", "and in", "in reactome", "reactome pathways", "as mll2", "mll4 have", "have been", "been used", "used as", "as synonyms", "synonyms for", "for both", "both kmt2b", "kmt2b and", "on whether", "whether the", "the numbering", "numbering of", "of mlls", "mlls referred", "referred to", "to order", "order of", "of cloning", "cloning or", "or whether", "whether it", "it referred", "to similarity", "similarity to", "to founding", "founding mll1", "enzyme. the", "the current", "current uniprot", "uniprot standard", "standard is", "is for", "for mll2", "mll2 to", "to be", "be used", "the preferred", "preferred synonym", "synonym of", "of kmt2b", "and for", "for mll4", "mll4 to", "of kmt2d.", "wdr5 is a", "is a component", "a component of", "component of six", "of six mammalian", "six mammalian histone", "mammalian histone methyltransferase", "histone methyltransferase kmt2", "methyltransferase kmt2 complexes:", "kmt2 complexes: mixed", "complexes: mixed lineage", "mixed lineage leukemia", "leukemia mll", "mll 1", "4 set1a", "set1a and", "and set1b. all", "set1b. all kmt2", "all kmt2 complexes", "kmt2 complexes consist", "complexes consist of", "consist of a", "of a histone", "a histone methyltransferase", "methyltransferase kmt2a", "kmt2a kmt2b", "kmt2b kmt2c", "kmt2c kmt2d", "kmt2d setd1a", "setd1a or", "setd1b respectively", "respectively and", "and the wrad", "the wrad subcomplex", "wrad subcomplex composed", "subcomplex composed of", "composed of wdr5", "wdr5 rbbp5", "rbbp5 ash2l", "ash2l and", "and dpy30. the", "dpy30. the wrad", "the wrad complex", "wrad complex regulates", "complex regulates the", "regulates the enzymatic", "the enzymatic activity", "enzymatic activity of", "activity of histone", "of histone methyltransferases", "histone methyltransferases and", "methyltransferases and enables", "and enables their", "enables their recruitment", "their recruitment to", "recruitment to chromatin.", "to chromatin. additional", "chromatin. additional transcription", "additional transcription cofactors", "transcription cofactors associate", "cofactors associate with", "associate with each", "with each kmt2", "each kmt2 histone", "kmt2 histone methyltransferase", "histone methyltransferase complex", "complex enabling", "enabling their functional", "their functional diversification.", "functional diversification. for", "diversification. for a", "for a detailed", "a detailed overview", "overview please", "please refer to", "refer to cho", "to cho et", "cho et al.", "et al. 2007", "2007 song", "song and kingston", "and kingston 2008", "2008 takahashi", "takahashi et al.", "et al. 2011", "2011 couture", "couture and skiniotis", "and skiniotis 2013", "2013 van", "van nuland et", "nuland et al.", "et al. 2013", "2013 klonou", "klonou et al.", "et al. 2021.

              the", "al. 2021.

              the kmt2", "2021.

              the kmt2 complexes", "kmt2 complexes are", "complexes are evolutionarily", "are evolutionarily conserved.", "evolutionarily conserved. while", "conserved. while a", "while a single", "a single set1/compass", "single set1/compass complex", "set1/compass complex is", "complex is present", "is present in", "present in yeast", "yeast three", "three distinct complexes", "distinct complexes are", "complexes are present", "are present in", "present in drosophila:", "in drosophila: trithorax", "trithorax trx", "related trr", "and set1. in", "set1. in mammals", "mammals due", "due to gene", "to gene duplication", "duplication two", "two trx like", "trx like complexes", "complexes one", "one with kmt2a", "with kmt2a and", "kmt2a and another", "and another with", "another with kmt2b", "with kmt2b as", "kmt2b as the", "as the catalytic", "the catalytic subunit", "as well as", "well as two", "as two trr", "two trr like", "trr like complexes", "one with kmt2c", "with kmt2c and", "kmt2c and another", "another with kmt2d", "with kmt2d as", "kmt2d as the", "and two set1", "two set1 like", "set1 like complexes", "one with setd1a", "with setd1a and", "setd1a and another", "another with setd1b", "with setd1b as", "setd1b as the", "subunit are", "are formed. for", "formed. for review", "review please", "refer to rao", "to rao and", "rao and dou", "and dou 2015.

              all", "dou 2015.

              all kmt2", "2015.

              all kmt2 complexes", "kmt2 complexes methylate", "complexes methylate lysine", "methylate lysine k5", "lysine k5 of", "k5 of histone", "of histone h3", "h3 k4", "k4 in mature", "in mature histone", "mature histone h3", "histone h3 peptides", "peptides as", "as the initiator", "the initiator methionine", "initiator methionine is", "methionine is removed", "which is associated", "is associated with", "associated with transcriptional", "with transcriptional activation.", "transcriptional activation. different", "activation. different kmt2", "different kmt2 complexes", "kmt2 complexes preferentially", "complexes preferentially monomethylate", "monomethylate dimethylate", "dimethylate or", "or trimethylate h3k4", "h3k4 depending", "depending on the", "on the presence", "the presence of", "presence of accessory", "of accessory subunits", "subunits transcriptional", "transcriptional co factors", "factors and", "and posttranslational modifications.", "posttranslational modifications. the", "modifications. the catalytic", "the catalytic activity", "catalytic activity of", "activity of kmt2", "of kmt2 complexes", "kmt2 complexes may", "complexes may differ", "may differ between", "differ between endogenous", "between endogenous complexes", "endogenous complexes and", "complexes and complexes", "and complexes reconstituted", "complexes reconstituted in", "reconstituted in vitro", "in vitro by", "vitro by mammalian", "by mammalian proteins", "mammalian proteins expressed", "proteins expressed and", "expressed and produced", "and produced in", "produced in bacterial", "in bacterial or", "bacterial or insect", "or insect cells.", "insect cells. the", "cells. the kmt2a", "the kmt2a and", "kmt2a and kmt2b", "and kmt2b complexes", "kmt2b complexes preferentially", "complexes preferentially methylate", "preferentially methylate h3k4", "methylate h3k4 at", "h3k4 at a", "at a limited", "a limited number", "limited number of", "number of target", "of target gene", "target gene promoters", "promoters while", "while kmt2c and", "kmt2c and kmt2d", "and kmt2d complexes", "kmt2d complexes preferentially", "target gene enhancers.", "gene enhancers. setd1a", "enhancers. setd1a and", "setd1a and setd1b", "and setd1b complexes", "setd1b complexes are", "complexes are responsible", "are responsible for", "responsible for the", "for the bulk", "the bulk of", "bulk of cellular", "of cellular h3k4", "cellular h3k4 methylation", "h3k4 methylation and", "methylation and show", "and show less", "show less target", "less target specificity.", "target specificity. for", "specificity. for overview", "refer to patel", "to patel et", "patel et al.", "et al. 2009", "2009 wang", "wang et al.", "2009 rao", "and dou 2015.

              in", "dou 2015.

              in both", "2015.

              in both drosophila", "both drosophila and", "drosophila and vertebrates", "vertebrates kmt2", "kmt2 complexes control", "complexes control the", "control the expression", "the expression of", "expression of evolutionarily", "of evolutionarily conserved", "evolutionarily conserved hox", "conserved hox genes", "hox genes which", "genes which serve", "which serve as", "serve as master", "as master regulators", "master regulators of", "regulators of embryonic", "of embryonic patterning", "patterning reviewed", "reviewed in soshnikova", "in soshnikova and", "soshnikova and duboule", "and duboule 2009", "duboule 2009 .

              germline", "2009 .

              germline mutations", ".

              germline mutations in", "mutations in human", "in human kmt2", "human kmt2 complexes", "complexes are the", "are the underlying", "the underlying cause", "underlying cause of", "cause of several", "of several chromatinopathies.", "several chromatinopathies. germline", "chromatinopathies. germline loss", "germline loss of", "loss of function", "function lof", "mutations in kmt2a", "in kmt2a cause", "kmt2a cause weideman", "cause weideman steiner", "weideman steiner syndrome", "syndrome a", "a rare autosomal", "rare autosomal dominant", "autosomal dominant disorder", "dominant disorder characterized", "disorder characterized by", "characterized by intellectual", "by intellectual disability", "disability developmental", "delay pre", "pre and", "and post natal", "post natal growth", "natal growth delay", "delay hypertrichosis", "hypertrichosis short", "stature hypotonia", "hypotonia distinctive", "distinctive facial features", "features skeletal", "abnormalities feeding", "feeding problems and", "problems and behavioral", "and behavioral difficulties", "difficulties reviewed", "reviewed in castiglioni", "in castiglioni et", "castiglioni et al.", "et al. 2022", "al. 2022 .", "2022 . germline", ". germline lof", "germline lof mutations", "lof mutations in", "mutations in kmt2b", "in kmt2b cause", "kmt2b cause dystonia", "cause dystonia 28", "28 dyt28", "dyt28 and", "and intellectual developmental", "developmental autosomal", "dominant disorder 68", "68 mrd68", "mrd68 . dyt28", ". dyt28 is", "dyt28 is an", "is an autosomal", "an autosomal dominant", "autosomal dominant neurologic", "dominant neurologic disorder", "neurologic disorder characterized", "characterized by onset", "by onset of", "onset of progressive", "of progressive dystonia", "progressive dystonia in", "dystonia in the", "in the first", "the first decade", "first decade of", "decade of life", "life reviewed", "reviewed in zech", "in zech et", "zech et al.", "et al. 2019", "while mrd68 is", "mrd68 is an", "characterized by developmental", "by developmental delay/intellectual", "developmental delay/intellectual disability", "disability microcephaly", "microcephaly poor", "growth feeding", "difficulties and", "and dysmorphic features", "features cif", "cif et al.", "et al. 2020", "al. 2020 .", "2020 . germline", "mutations in kmt2c", "in kmt2c cause", "kmt2c cause kleefstra", "cause kleefstra syndrome", "kleefstra syndrome 2", "2 klefs2", "autosomal dominant neurodevelopmental", "dominant neurodevelopmental disorder", "neurodevelopmental disorder characterized", "characterized by delayed", "by delayed psychomotor", "delayed psychomotor development", "development variable", "variable intellectual disability", "disability and", "and mild dysmorphic", "mild dysmorphic features", "features reviewed", "reviewed in lavery", "in lavery et", "lavery et al.", "mutations in kmt2d", "in kmt2d cause", "kmt2d cause kabuki", "cause kabuki syndrome", "kabuki syndrome 1", "1 a", "a congenital mental", "congenital mental retardation", "mental retardation syndrome", "retardation syndrome with", "syndrome with postnatal", "with postnatal dwarfism", "dwarfism a", "a facial dysmorphism", "facial dysmorphism and", "dysmorphism and skeletal", "and skeletal abnormalities", "abnormalities reviewed", "mutations in setd1a", "in setd1a cause", "setd1a cause early", "cause early onset", "early onset epilepsy", "onset epilepsy with", "epilepsy with or", "with or without", "or without developmental", "without developmental delay", "delay epedd", "disorder yu", "yu et al.", "and neurodevelopmental disorder", "neurodevelopmental disorder with", "disorder with speech", "with speech impairment", "speech impairment and", "impairment and dysmorphic", "and dysmorphic facies", "facies nedsid", "kummeling et al.", "et al. 2021", "al. 2021 .", "2021 . germline", "mutations in setd1b", "in setd1b cause", "setd1b cause intellectual", "cause intellectual developmental", "intellectual developmental disorder", "developmental disorder with", "disorder with seizures", "with seizures and", "seizures and language", "and language delay", "delay iddseld", "roston et al.", "al. 2021 .

              somatic", "2021 .

              somatic mutations", ".

              somatic mutations in", "mutations in kmt2", "in kmt2 genes", "kmt2 genes contribute", "genes contribute to", "contribute to cancer", "to cancer development.", "cancer development. they", "development. they were", "they were first", "were first discovered", "first discovered in", "discovered in mixed", "in mixed lineage", "characterized by chromosomal", "by chromosomal translocations", "chromosomal translocations that", "translocations that involve", "that involve the", "involve the kmt2a", "the kmt2a gene", "kmt2a gene locus", "gene locus on", "locus on chromosome", "on chromosome 11", "11 chromosomal", "chromosomal band 11q23", "11q23 and", "and result in", "result in the", "in the expression", "expression of fusion", "of fusion proteins", "fusion proteins with", "proteins with oncogenic", "with oncogenic properties.", "oncogenic properties. besides", "properties. besides gene", "besides gene fusions", "fusions other", "other types of", "types of kmt2a", "of kmt2a mutations", "kmt2a mutations are", "mutations are also", "are also present", "also present in", "present in blood", "in blood cancers", "cancers most", "most frequently in", "frequently in high", "in high grade", "high grade b", "grade b cell", "b cell lymphoma", "lymphoma t", "t cell lymphoblastic", "cell lymphoblastic leukemia", "leukemia and", "and acute myeloid", "acute myeloid leukemia", "and solid tumors", "tumors most", "most often reported", "often reported in", "reported in lung", "in lung adenocarcinoma", "adenocarcinoma colon", "adenocarcinoma and", "and bladder urothelial", "bladder urothelial carcinoma", "urothelial carcinoma .", "carcinoma . somatic", ". somatic cancer", "somatic cancer mutations", "cancer mutations in", "mutations in other", "in other kmt2", "other kmt2 genes", "genes kmt2b", "setd1b are", "are less characterized", "less characterized but", "characterized but most", "but most frequently", "most frequently affect", "frequently affect the", "affect the catalytic", "the catalytic set", "catalytic set domain", "set domain and", "domain and show", "and show different", "show different distributions", "different distributions between", "distributions between different", "between different cancer", "different cancer types.", "cancer types. for", "types. for review", "and dou 2015", "2015 castiglioni", "et al. 2022.", "al. 2022. several", "2022. several anti", "several anti cancer", "anti cancer therapeutics", "cancer therapeutics are", "therapeutics are being", "are being developed", "being developed that", "developed that affect", "that affect the", "affect the association", "the association of", "association of kmt2", "of kmt2 enzymes", "kmt2 enzymes with", "enzymes with components", "with components of", "components of the", "of the wrad", "complex in", "in particular wdr5", "wdr5 reviewed", "reviewed in vedadi", "in vedadi et", "vedadi et al.", "et al. 2017", "2017 siladi", "siladi et al.", "al. 2022 .

              wdr5", "2022 .

              wdr5 is", ".

              wdr5 is also", "is also a", "also a component", "component of three", "of three histone", "three histone acetyltransferase", "histone acetyltransferase complexes", "complexes gcn5", "atac pcaf", "atac and", "and mof/kat8 nsl.", "mof/kat8 nsl. the", "nsl. the role", "the role of", "role of wdr5", "of wdr5 in", "wdr5 in epigenetic", "in epigenetic regulation", "epigenetic regulation of", "regulation of gene", "of gene expression", "gene expression through", "expression through histone", "through histone acetylation", "histone acetylation is", "acetylation is under", "is under investigation", "investigation reviewed", "reviewed in guarnaccia", "in guarnaccia and", "guarnaccia and tansey", "and tansey 2018", "tansey 2018 .

              the", "2018 .

              the function", ".

              the function of", "function of wdr5", "modifying complexes is", "complexes is currently", "is currently depicted", "currently depicted in", "depicted in the", "in the following", "the following reactome", "following reactome pathways:", "reactome pathways: \\transcriptional", "pathways: \\transcriptional regulation", "\\transcriptional regulation of", "regulation of granulopoiesis\\", "granulopoiesis\\ mll1", "\\transcriptional regulation by", "regulation by runx1\\", "runx1\\ mll1", "\\activation of anterior", "of anterior hox", "anterior hox genes", "hox genes in", "genes in hindbrain", "in hindbrain development", "hindbrain development during", "development during early", "during early embryogenesis\\", "embryogenesis\\ mll3", "mll3 complex and", "complex and mll4", "and mll4 complex", "\\tcf dependent signaling", "dependent signaling in", "signaling in response", "in response to", "response to wnt\\", "wnt\\ mll4", "and \\chromatin organization\\", "organization\\ mll1", "complex mll2", "complex mll3", "complex mll4", "complex set1a", "complex set1b", "complex gcn5", "gcn5 atac complex", "complex pcaf", "pcaf atac complex", "and mof/kat8 nsl", "mof/kat8 nsl complex", "nsl complex .", "complex . please", ". please note", "please note that", "note that there", "that there is", "there is an", "is an inconsistency", "an inconsistency in", "inconsistency in naming", "in naming of", "naming of mll2", "of mll2 and", "mll2 and mll4", "and mll4 complexes", "mll4 complexes in", "complexes in the", "in the literature", "the literature and", "literature and in", "and in reactome", "in reactome pathways", "pathways as", "as mll2 and", "and mll4 have", "mll4 have been", "have been used", "been used as", "used as synonyms", "as synonyms for", "synonyms for both", "for both kmt2b", "both kmt2b and", "kmt2b and kmt2d", "kmt2d depending", "depending on whether", "on whether the", "whether the numbering", "the numbering of", "numbering of mlls", "of mlls referred", "mlls referred to", "referred to order", "to order of", "order of cloning", "of cloning or", "cloning or whether", "or whether it", "whether it referred", "it referred to", "referred to similarity", "to similarity to", "similarity to founding", "to founding mll1", "mll1 mll", "mll kmt2a", "kmt2a enzyme.", "enzyme. the current", "the current uniprot", "current uniprot standard", "uniprot standard is", "standard is for", "is for mll2", "for mll2 to", "mll2 to be", "to be used", "be used as", "used as the", "as the preferred", "the preferred synonym", "preferred synonym of", "synonym of kmt2b", "and for mll4", "for mll4 to", "mll4 to be", "synonym of kmt2d.", "wdr5 is a component", "is a component of", "a component of six", "component of six mammalian", "of six mammalian histone", "six mammalian histone methyltransferase", "mammalian histone methyltransferase kmt2", "histone methyltransferase kmt2 complexes:", "methyltransferase kmt2 complexes: mixed", "kmt2 complexes: mixed lineage", "complexes: mixed lineage leukemia", "lineage leukemia mll", "mll 1 4", "1 4 set1a", "set1a and set1b.", "and set1b. all kmt2", "set1b. all kmt2 complexes", "all kmt2 complexes consist", "kmt2 complexes consist of", "complexes consist of a", "consist of a histone", "of a histone methyltransferase", "histone methyltransferase kmt2a", "setd1a or setd1b", "or setd1b respectively", "respectively and the", "and the wrad subcomplex", "the wrad subcomplex composed", "wrad subcomplex composed of", "subcomplex composed of wdr5", "of wdr5 rbbp5", "ash2l and dpy30.", "and dpy30. the wrad", "dpy30. the wrad complex", "the wrad complex regulates", "wrad complex regulates the", "complex regulates the enzymatic", "regulates the enzymatic activity", "the enzymatic activity of", "enzymatic activity of histone", "activity of histone methyltransferases", "of histone methyltransferases and", "histone methyltransferases and enables", "methyltransferases and enables their", "and enables their recruitment", "enables their recruitment to", "their recruitment to chromatin.", "recruitment to chromatin. additional", "to chromatin. additional transcription", "chromatin. additional transcription cofactors", "additional transcription cofactors associate", "transcription cofactors associate with", "cofactors associate with each", "associate with each kmt2", "with each kmt2 histone", "each kmt2 histone methyltransferase", "kmt2 histone methyltransferase complex", "methyltransferase complex enabling", "complex enabling their", "enabling their functional diversification.", "their functional diversification. for", "functional diversification. for a", "diversification. for a detailed", "for a detailed overview", "detailed overview please", "overview please refer", "please refer to cho", "refer to cho et", "to cho et al.", "cho et al. 2007", "al. 2007 song", "2007 song and", "song and kingston 2008", "kingston 2008 takahashi", "2008 takahashi et", "takahashi et al. 2011", "al. 2011 couture", "2011 couture and", "couture and skiniotis 2013", "skiniotis 2013 van", "2013 van nuland", "van nuland et al.", "nuland et al. 2013", "al. 2013 klonou", "2013 klonou et", "klonou et al. 2021.

              the", "et al. 2021.

              the kmt2", "al. 2021.

              the kmt2 complexes", "2021.

              the kmt2 complexes are", "kmt2 complexes are evolutionarily", "complexes are evolutionarily conserved.", "are evolutionarily conserved. while", "evolutionarily conserved. while a", "conserved. while a single", "while a single set1/compass", "a single set1/compass complex", "single set1/compass complex is", "set1/compass complex is present", "complex is present in", "is present in yeast", "in yeast three", "yeast three distinct", "three distinct complexes are", "distinct complexes are present", "complexes are present in", "are present in drosophila:", "present in drosophila: trithorax", "drosophila: trithorax trx", "trx trithorax", "trithorax related trr", "trr and", "and set1. in mammals", "in mammals due", "mammals due to", "due to gene duplication", "gene duplication two", "duplication two trx", "two trx like complexes", "like complexes one", "complexes one with", "one with kmt2a and", "with kmt2a and another", "kmt2a and another with", "and another with kmt2b", "another with kmt2b as", "with kmt2b as the", "kmt2b as the catalytic", "as the catalytic subunit", "subunit as", "as well as two", "well as two trr", "as two trr like", "two trr like complexes", "one with kmt2c and", "with kmt2c and another", "kmt2c and another with", "and another with kmt2d", "another with kmt2d as", "with kmt2d as the", "kmt2d as the catalytic", "subunit and", "and two set1 like", "two set1 like complexes", "one with setd1a and", "with setd1a and another", "setd1a and another with", "and another with setd1b", "another with setd1b as", "with setd1b as the", "setd1b as the catalytic", "catalytic subunit are", "subunit are formed.", "are formed. for review", "for review please", "review please refer", "please refer to rao", "refer to rao and", "to rao and dou", "rao and dou 2015.

              all", "and dou 2015.

              all kmt2", "dou 2015.

              all kmt2 complexes", "2015.

              all kmt2 complexes methylate", "kmt2 complexes methylate lysine", "complexes methylate lysine k5", "methylate lysine k5 of", "lysine k5 of histone", "k5 of histone h3", "histone h3 k4", "h3 k4 in", "k4 in mature histone", "in mature histone h3", "mature histone h3 peptides", "h3 peptides as", "peptides as the", "as the initiator methionine", "the initiator methionine is", "initiator methionine is removed", "removed which", "which is associated with", "is associated with transcriptional", "associated with transcriptional activation.", "with transcriptional activation. different", "transcriptional activation. different kmt2", "activation. different kmt2 complexes", "different kmt2 complexes preferentially", "kmt2 complexes preferentially monomethylate", "preferentially monomethylate dimethylate", "dimethylate or trimethylate", "trimethylate h3k4 depending", "h3k4 depending on", "depending on the presence", "on the presence of", "the presence of accessory", "presence of accessory subunits", "accessory subunits transcriptional", "subunits transcriptional co", "co factors and", "factors and posttranslational", "and posttranslational modifications. the", "posttranslational modifications. the catalytic", "modifications. the catalytic activity", "the catalytic activity of", "catalytic activity of kmt2", "activity of kmt2 complexes", "of kmt2 complexes may", "kmt2 complexes may differ", "complexes may differ between", "may differ between endogenous", "differ between endogenous complexes", "between endogenous complexes and", "endogenous complexes and complexes", "complexes and complexes reconstituted", "and complexes reconstituted in", "complexes reconstituted in vitro", "reconstituted in vitro by", "in vitro by mammalian", "vitro by mammalian proteins", "by mammalian proteins expressed", "mammalian proteins expressed and", "proteins expressed and produced", "expressed and produced in", "and produced in bacterial", "produced in bacterial or", "in bacterial or insect", "bacterial or insect cells.", "or insect cells. the", "insect cells. the kmt2a", "cells. the kmt2a and", "the kmt2a and kmt2b", "kmt2a and kmt2b complexes", "and kmt2b complexes preferentially", "kmt2b complexes preferentially methylate", "complexes preferentially methylate h3k4", "preferentially methylate h3k4 at", "methylate h3k4 at a", "h3k4 at a limited", "at a limited number", "a limited number of", "limited number of target", "number of target gene", "of target gene promoters", "gene promoters while", "promoters while kmt2c", "while kmt2c and kmt2d", "kmt2c and kmt2d complexes", "and kmt2d complexes preferentially", "kmt2d complexes preferentially methylate", "of target gene enhancers.", "target gene enhancers. setd1a", "gene enhancers. setd1a and", "enhancers. setd1a and setd1b", "setd1a and setd1b complexes", "and setd1b complexes are", "setd1b complexes are responsible", "complexes are responsible for", "are responsible for the", "responsible for the bulk", "for the bulk of", "the bulk of cellular", "bulk of cellular h3k4", "of cellular h3k4 methylation", "cellular h3k4 methylation and", "h3k4 methylation and show", "methylation and show less", "and show less target", "show less target specificity.", "less target specificity. for", "target specificity. for overview", "for overview please", "please refer to patel", "refer to patel et", "to patel et al.", "patel et al. 2009", "al. 2009 wang", "2009 wang et", "wang et al. 2009", "al. 2009 rao", "2009 rao and", "rao and dou 2015.

              in", "and dou 2015.

              in both", "dou 2015.

              in both drosophila", "2015.

              in both drosophila and", "both drosophila and vertebrates", "and vertebrates kmt2", "vertebrates kmt2 complexes", "kmt2 complexes control the", "complexes control the expression", "control the expression of", "the expression of evolutionarily", "expression of evolutionarily conserved", "of evolutionarily conserved hox", "evolutionarily conserved hox genes", "conserved hox genes which", "hox genes which serve", "genes which serve as", "which serve as master", "serve as master regulators", "as master regulators of", "master regulators of embryonic", "regulators of embryonic patterning", "embryonic patterning reviewed", "patterning reviewed in", "reviewed in soshnikova and", "in soshnikova and duboule", "soshnikova and duboule 2009", "and duboule 2009 .

              germline", "duboule 2009 .

              germline mutations", "2009 .

              germline mutations in", ".

              germline mutations in human", "mutations in human kmt2", "in human kmt2 complexes", "human kmt2 complexes are", "kmt2 complexes are the", "complexes are the underlying", "are the underlying cause", "the underlying cause of", "underlying cause of several", "cause of several chromatinopathies.", "of several chromatinopathies. germline", "several chromatinopathies. germline loss", "chromatinopathies. germline loss of", "germline loss of function", "of function lof", "mutations in kmt2a cause", "in kmt2a cause weideman", "kmt2a cause weideman steiner", "cause weideman steiner syndrome", "steiner syndrome a", "syndrome a rare", "a rare autosomal dominant", "rare autosomal dominant disorder", "autosomal dominant disorder characterized", "dominant disorder characterized by", "disorder characterized by intellectual", "characterized by intellectual disability", "intellectual disability developmental", "disability developmental delay", "developmental delay pre", "pre and post", "and post natal growth", "post natal growth delay", "growth delay hypertrichosis", "hypertrichosis short stature", "short stature hypotonia", "hypotonia distinctive facial", "facial features skeletal", "features skeletal abnormalities", "skeletal abnormalities feeding", "abnormalities feeding problems", "feeding problems and behavioral", "problems and behavioral difficulties", "behavioral difficulties reviewed", "difficulties reviewed in", "reviewed in castiglioni et", "in castiglioni et al.", "castiglioni et al. 2022", "et al. 2022 .", "al. 2022 . germline", "2022 . germline lof", ". germline lof mutations", "germline lof mutations in", "lof mutations in kmt2b", "mutations in kmt2b cause", "in kmt2b cause dystonia", "kmt2b cause dystonia 28", "dystonia 28 dyt28", "dyt28 and intellectual", "intellectual developmental autosomal", "developmental autosomal dominant", "autosomal dominant disorder 68", "disorder 68 mrd68", "68 mrd68 .", "mrd68 . dyt28 is", ". dyt28 is an", "dyt28 is an autosomal", "is an autosomal dominant", "an autosomal dominant neurologic", "autosomal dominant neurologic disorder", "dominant neurologic disorder characterized", "neurologic disorder characterized by", "disorder characterized by onset", "characterized by onset of", "by onset of progressive", "onset of progressive dystonia", "of progressive dystonia in", "progressive dystonia in the", "dystonia in the first", "in the first decade", "the first decade of", "first decade of life", "of life reviewed", "life reviewed in", "reviewed in zech et", "in zech et al.", "zech et al. 2019", "2019 while", "while mrd68 is an", "mrd68 is an autosomal", "an autosomal dominant disorder", "disorder characterized by developmental", "characterized by developmental delay/intellectual", "by developmental delay/intellectual disability", "delay/intellectual disability microcephaly", "microcephaly poor growth", "poor growth feeding", "growth feeding difficulties", "feeding difficulties and", "difficulties and dysmorphic", "dysmorphic features cif", "features cif et", "cif et al. 2020", "et al. 2020 .", "al. 2020 . germline", "2020 . germline lof", "lof mutations in kmt2c", "mutations in kmt2c cause", "in kmt2c cause kleefstra", "kmt2c cause kleefstra syndrome", "cause kleefstra syndrome 2", "syndrome 2 klefs2", "klefs2 an", "an autosomal dominant neurodevelopmental", "autosomal dominant neurodevelopmental disorder", "dominant neurodevelopmental disorder characterized", "neurodevelopmental disorder characterized by", "disorder characterized by delayed", "characterized by delayed psychomotor", "by delayed psychomotor development", "psychomotor development variable", "development variable intellectual", "intellectual disability and", "disability and mild", "and mild dysmorphic features", "dysmorphic features reviewed", "features reviewed in", "reviewed in lavery et", "in lavery et al.", "lavery et al. 2020", "lof mutations in kmt2d", "mutations in kmt2d cause", "in kmt2d cause kabuki", "kmt2d cause kabuki syndrome", "cause kabuki syndrome 1", "syndrome 1 a", "1 a congenital", "a congenital mental retardation", "congenital mental retardation syndrome", "mental retardation syndrome with", "retardation syndrome with postnatal", "syndrome with postnatal dwarfism", "postnatal dwarfism a", "dwarfism a facial", "a facial dysmorphism and", "facial dysmorphism and skeletal", "dysmorphism and skeletal abnormalities", "skeletal abnormalities reviewed", "abnormalities reviewed in", "lof mutations in setd1a", "mutations in setd1a cause", "in setd1a cause early", "setd1a cause early onset", "cause early onset epilepsy", "early onset epilepsy with", "onset epilepsy with or", "epilepsy with or without", "with or without developmental", "or without developmental delay", "developmental delay epedd", "epedd an", "neurologic disorder yu", "disorder yu et", "yu et al. 2019", "2019 and", "and neurodevelopmental disorder with", "neurodevelopmental disorder with speech", "disorder with speech impairment", "with speech impairment and", "speech impairment and dysmorphic", "impairment and dysmorphic facies", "dysmorphic facies nedsid", "nedsid kummeling", "kummeling et al. 2021", "et al. 2021 .", "al. 2021 . germline", "2021 . germline lof", "lof mutations in setd1b", "mutations in setd1b cause", "in setd1b cause intellectual", "setd1b cause intellectual developmental", "cause intellectual developmental disorder", "intellectual developmental disorder with", "developmental disorder with seizures", "disorder with seizures and", "with seizures and language", "seizures and language delay", "language delay iddseld", "iddseld roston", "roston et al. 2021", "et al. 2021 .

              somatic", "al. 2021 .

              somatic mutations", "2021 .

              somatic mutations in", ".

              somatic mutations in kmt2", "mutations in kmt2 genes", "in kmt2 genes contribute", "kmt2 genes contribute to", "genes contribute to cancer", "contribute to cancer development.", "to cancer development. they", "cancer development. they were", "development. they were first", "they were first discovered", "were first discovered in", "first discovered in mixed", "discovered in mixed lineage", "in mixed lineage leukemia", "mll characterized", "characterized by chromosomal translocations", "by chromosomal translocations that", "chromosomal translocations that involve", "translocations that involve the", "that involve the kmt2a", "involve the kmt2a gene", "the kmt2a gene locus", "kmt2a gene locus on", "gene locus on chromosome", "locus on chromosome 11", "chromosome 11 chromosomal", "11 chromosomal band", "band 11q23 and", "11q23 and result", "and result in the", "result in the expression", "in the expression of", "the expression of fusion", "expression of fusion proteins", "of fusion proteins with", "fusion proteins with oncogenic", "proteins with oncogenic properties.", "with oncogenic properties. besides", "oncogenic properties. besides gene", "properties. besides gene fusions", "gene fusions other", "fusions other types", "other types of kmt2a", "types of kmt2a mutations", "of kmt2a mutations are", "kmt2a mutations are also", "mutations are also present", "are also present in", "also present in blood", "present in blood cancers", "blood cancers most", "cancers most frequently", "most frequently in high", "frequently in high grade", "in high grade b", "high grade b cell", "grade b cell lymphoma", "cell lymphoma t", "lymphoma t cell", "t cell lymphoblastic leukemia", "lymphoblastic leukemia and", "leukemia and acute", "and acute myeloid leukemia", "myeloid leukemia and", "leukemia and solid", "solid tumors most", "tumors most often", "most often reported in", "often reported in lung", "reported in lung adenocarcinoma", "lung adenocarcinoma colon", "adenocarcinoma colon adenocarcinoma", "colon adenocarcinoma and", "adenocarcinoma and bladder", "and bladder urothelial carcinoma", "bladder urothelial carcinoma .", "urothelial carcinoma . somatic", "carcinoma . somatic cancer", ". somatic cancer mutations", "somatic cancer mutations in", "cancer mutations in other", "mutations in other kmt2", "in other kmt2 genes", "kmt2 genes kmt2b", "kmt2d setd1a and", "and setd1b are", "setd1b are less", "are less characterized but", "less characterized but most", "characterized but most frequently", "but most frequently affect", "most frequently affect the", "frequently affect the catalytic", "affect the catalytic set", "the catalytic set domain", "catalytic set domain and", "set domain and show", "domain and show different", "and show different distributions", "show different distributions between", "different distributions between different", "distributions between different cancer", "between different cancer types.", "different cancer types. for", "cancer types. for review", "rao and dou 2015", "dou 2015 castiglioni", "2015 castiglioni et", "castiglioni et al. 2022.", "et al. 2022. several", "al. 2022. several anti", "2022. several anti cancer", "several anti cancer therapeutics", "anti cancer therapeutics are", "cancer therapeutics are being", "therapeutics are being developed", "are being developed that", "being developed that affect", "developed that affect the", "that affect the association", "affect the association of", "the association of kmt2", "association of kmt2 enzymes", "of kmt2 enzymes with", "kmt2 enzymes with components", "enzymes with components of", "with components of the", "components of the wrad", "of the wrad complex", "wrad complex in", "complex in particular", "particular wdr5 reviewed", "wdr5 reviewed in", "reviewed in vedadi et", "in vedadi et al.", "vedadi et al. 2017", "al. 2017 siladi", "2017 siladi et", "siladi et al. 2022", "et al. 2022 .

              wdr5", "al. 2022 .

              wdr5 is", "2022 .

              wdr5 is also", ".

              wdr5 is also a", "is also a component", "also a component of", "a component of three", "component of three histone", "of three histone acetyltransferase", "three histone acetyltransferase complexes", "acetyltransferase complexes gcn5", "complexes gcn5 atac", "gcn5 atac pcaf", "atac pcaf atac", "pcaf atac and", "atac and mof/kat8", "and mof/kat8 nsl. the", "mof/kat8 nsl. the role", "nsl. the role of", "the role of wdr5", "role of wdr5 in", "of wdr5 in epigenetic", "wdr5 in epigenetic regulation", "in epigenetic regulation of", "epigenetic regulation of gene", "regulation of gene expression", "of gene expression through", "gene expression through histone", "expression through histone acetylation", "through histone acetylation is", "histone acetylation is under", "acetylation is under investigation", "under investigation reviewed", "investigation reviewed in", "reviewed in guarnaccia and", "in guarnaccia and tansey", "guarnaccia and tansey 2018", "and tansey 2018 .

              the", "tansey 2018 .

              the function", "2018 .

              the function of", ".

              the function of wdr5", "function of wdr5 containing", "histone modifying complexes is", "modifying complexes is currently", "complexes is currently depicted", "is currently depicted in", "currently depicted in the", "depicted in the following", "in the following reactome", "the following reactome pathways:", "following reactome pathways: \\transcriptional", "reactome pathways: \\transcriptional regulation", "pathways: \\transcriptional regulation of", "\\transcriptional regulation of granulopoiesis\\", "of granulopoiesis\\ mll1", "granulopoiesis\\ mll1 complex", "complex \\transcriptional", "\\transcriptional regulation by runx1\\", "by runx1\\ mll1", "runx1\\ mll1 complex", "complex \\activation", "\\activation of anterior hox", "of anterior hox genes", "anterior hox genes in", "hox genes in hindbrain", "genes in hindbrain development", "in hindbrain development during", "hindbrain development during early", "development during early embryogenesis\\", "early embryogenesis\\ mll3", "embryogenesis\\ mll3 complex", "mll3 complex and mll4", "complex and mll4 complex", "complex \\tcf", "\\tcf dependent signaling in", "dependent signaling in response", "signaling in response to", "in response to wnt\\", "to wnt\\ mll4", "wnt\\ mll4 complex", "\\chromatin organization\\ mll1", "organization\\ mll1 complex", "mll1 complex mll2", "complex mll2 complex", "mll2 complex mll3", "complex mll3 complex", "mll3 complex mll4", "complex mll4 complex", "mll4 complex set1a", "complex set1a complex", "set1a complex set1b", "complex set1b complex", "set1b complex gcn5", "complex gcn5 atac", "atac complex pcaf", "complex pcaf atac", "atac complex and", "complex and mof/kat8", "and mof/kat8 nsl complex", "mof/kat8 nsl complex .", "nsl complex . please", "complex . please note", ". please note that", "please note that there", "note that there is", "that there is an", "there is an inconsistency", "is an inconsistency in", "an inconsistency in naming", "inconsistency in naming of", "in naming of mll2", "naming of mll2 and", "of mll2 and mll4", "mll2 and mll4 complexes", "and mll4 complexes in", "mll4 complexes in the", "complexes in the literature", "in the literature and", "the literature and in", "literature and in reactome", "and in reactome pathways", "reactome pathways as", "pathways as mll2", "as mll2 and mll4", "mll2 and mll4 have", "and mll4 have been", "mll4 have been used", "have been used as", "been used as synonyms", "used as synonyms for", "as synonyms for both", "synonyms for both kmt2b", "for both kmt2b and", "both kmt2b and kmt2d", "and kmt2d depending", "kmt2d depending on", "depending on whether the", "on whether the numbering", "whether the numbering of", "the numbering of mlls", "numbering of mlls referred", "of mlls referred to", "mlls referred to order", "referred to order of", "to order of cloning", "order of cloning or", "of cloning or whether", "cloning or whether it", "or whether it referred", "whether it referred to", "it referred to similarity", "referred to similarity to", "to similarity to founding", "similarity to founding mll1", "founding mll1 mll", "kmt2a enzyme. the", "enzyme. the current uniprot", "the current uniprot standard", "current uniprot standard is", "uniprot standard is for", "standard is for mll2", "is for mll2 to", "for mll2 to be", "mll2 to be used", "to be used as", "be used as the", "used as the preferred", "as the preferred synonym", "the preferred synonym of", "preferred synonym of kmt2b", "of kmt2b and", "kmt2b and for", "and for mll4 to", "for mll4 to be", "mll4 to be used", "preferred synonym of kmt2d.", "wdr5 is a component of", "is a component of six", "a component of six mammalian", "component of six mammalian histone", "of six mammalian histone methyltransferase", "six mammalian histone methyltransferase kmt2", "mammalian histone methyltransferase kmt2 complexes:", "histone methyltransferase kmt2 complexes: mixed", "methyltransferase kmt2 complexes: mixed lineage", "kmt2 complexes: mixed lineage leukemia", "mixed lineage leukemia mll", "leukemia mll 1", "4 set1a and", "set1a and set1b. all", "and set1b. all kmt2 complexes", "set1b. all kmt2 complexes consist", "all kmt2 complexes consist of", "kmt2 complexes consist of a", "complexes consist of a histone", "consist of a histone methyltransferase", "a histone methyltransferase kmt2a", "methyltransferase kmt2a kmt2b", "kmt2a kmt2b kmt2c", "kmt2b kmt2c kmt2d", "kmt2c kmt2d setd1a", "kmt2d setd1a or", "setd1b respectively and", "respectively and the wrad", "and the wrad subcomplex composed", "the wrad subcomplex composed of", "wrad subcomplex composed of wdr5", "composed of wdr5 rbbp5", "wdr5 rbbp5 ash2l", "rbbp5 ash2l and", "ash2l and dpy30. the", "and dpy30. the wrad complex", "dpy30. the wrad complex regulates", "the wrad complex regulates the", "wrad complex regulates the enzymatic", "complex regulates the enzymatic activity", "regulates the enzymatic activity of", "the enzymatic activity of histone", "enzymatic activity of histone methyltransferases", "activity of histone methyltransferases and", "of histone methyltransferases and enables", "histone methyltransferases and enables their", "methyltransferases and enables their recruitment", "and enables their recruitment to", "enables their recruitment to chromatin.", "their recruitment to chromatin. additional", "recruitment to chromatin. additional transcription", "to chromatin. additional transcription cofactors", "chromatin. additional transcription cofactors associate", "additional transcription cofactors associate with", "transcription cofactors associate with each", "cofactors associate with each kmt2", "associate with each kmt2 histone", "with each kmt2 histone methyltransferase", "each kmt2 histone methyltransferase complex", "histone methyltransferase complex enabling", "methyltransferase complex enabling their", "complex enabling their functional", "enabling their functional diversification. for", "their functional diversification. for a", "functional diversification. for a detailed", "diversification. for a detailed overview", "a detailed overview please", "detailed overview please refer", "overview please refer to", "please refer to cho et", "refer to cho et al.", "to cho et al. 2007", "et al. 2007 song", "al. 2007 song and", "2007 song and kingston", "and kingston 2008 takahashi", "kingston 2008 takahashi et", "2008 takahashi et al.", "et al. 2011 couture", "al. 2011 couture and", "2011 couture and skiniotis", "and skiniotis 2013 van", "skiniotis 2013 van nuland", "2013 van nuland et", "van nuland et al. 2013", "et al. 2013 klonou", "al. 2013 klonou et", "2013 klonou et al.", "klonou et al. 2021.

              the kmt2", "et al. 2021.

              the kmt2 complexes", "al. 2021.

              the kmt2 complexes are", "2021.

              the kmt2 complexes are evolutionarily", "kmt2 complexes are evolutionarily conserved.", "complexes are evolutionarily conserved. while", "are evolutionarily conserved. while a", "evolutionarily conserved. while a single", "conserved. while a single set1/compass", "while a single set1/compass complex", "a single set1/compass complex is", "single set1/compass complex is present", "set1/compass complex is present in", "complex is present in yeast", "present in yeast three", "in yeast three distinct", "yeast three distinct complexes", "three distinct complexes are present", "distinct complexes are present in", "complexes are present in drosophila:", "are present in drosophila: trithorax", "in drosophila: trithorax trx", "trx trithorax related", "trr and set1.", "set1. in mammals due", "in mammals due to", "mammals due to gene", "to gene duplication two", "gene duplication two trx", "duplication two trx like", "trx like complexes one", "like complexes one with", "complexes one with kmt2a", "one with kmt2a and another", "with kmt2a and another with", "kmt2a and another with kmt2b", "and another with kmt2b as", "another with kmt2b as the", "with kmt2b as the catalytic", "kmt2b as the catalytic subunit", "catalytic subunit as", "subunit as well", "as well as two trr", "well as two trr like", "as two trr like complexes", "trr like complexes one", "complexes one with kmt2c", "one with kmt2c and another", "with kmt2c and another with", "kmt2c and another with kmt2d", "and another with kmt2d as", "another with kmt2d as the", "with kmt2d as the catalytic", "kmt2d as the catalytic subunit", "catalytic subunit and", "subunit and two", "and two set1 like complexes", "set1 like complexes one", "complexes one with setd1a", "one with setd1a and another", "with setd1a and another with", "setd1a and another with setd1b", "and another with setd1b as", "another with setd1b as the", "with setd1b as the catalytic", "setd1b as the catalytic subunit", "the catalytic subunit are", "catalytic subunit are formed.", "subunit are formed. for", "formed. for review please", "for review please refer", "review please refer to", "please refer to rao and", "refer to rao and dou", "to rao and dou 2015.

              all", "rao and dou 2015.

              all kmt2", "and dou 2015.

              all kmt2 complexes", "dou 2015.

              all kmt2 complexes methylate", "2015.

              all kmt2 complexes methylate lysine", "kmt2 complexes methylate lysine k5", "complexes methylate lysine k5 of", "methylate lysine k5 of histone", "lysine k5 of histone h3", "of histone h3 k4", "histone h3 k4 in", "h3 k4 in mature", "k4 in mature histone h3", "in mature histone h3 peptides", "histone h3 peptides as", "h3 peptides as the", "peptides as the initiator", "as the initiator methionine is", "the initiator methionine is removed", "is removed which", "removed which is", "which is associated with transcriptional", "is associated with transcriptional activation.", "associated with transcriptional activation. different", "with transcriptional activation. different kmt2", "transcriptional activation. different kmt2 complexes", "activation. different kmt2 complexes preferentially", "different kmt2 complexes preferentially monomethylate", "complexes preferentially monomethylate dimethylate", "monomethylate dimethylate or", "dimethylate or trimethylate h3k4", "or trimethylate h3k4 depending", "trimethylate h3k4 depending on", "h3k4 depending on the", "depending on the presence of", "on the presence of accessory", "the presence of accessory subunits", "of accessory subunits transcriptional", "accessory subunits transcriptional co", "subunits transcriptional co factors", "transcriptional co factors and", "co factors and posttranslational", "factors and posttranslational modifications.", "and posttranslational modifications. the catalytic", "posttranslational modifications. the catalytic activity", "modifications. the catalytic activity of", "the catalytic activity of kmt2", "catalytic activity of kmt2 complexes", "activity of kmt2 complexes may", "of kmt2 complexes may differ", "kmt2 complexes may differ between", "complexes may differ between endogenous", "may differ between endogenous complexes", "differ between endogenous complexes and", "between endogenous complexes and complexes", "endogenous complexes and complexes reconstituted", "complexes and complexes reconstituted in", "and complexes reconstituted in vitro", "complexes reconstituted in vitro by", "reconstituted in vitro by mammalian", "in vitro by mammalian proteins", "vitro by mammalian proteins expressed", "by mammalian proteins expressed and", "mammalian proteins expressed and produced", "proteins expressed and produced in", "expressed and produced in bacterial", "and produced in bacterial or", "produced in bacterial or insect", "in bacterial or insect cells.", "bacterial or insect cells. the", "or insect cells. the kmt2a", "insect cells. the kmt2a and", "cells. the kmt2a and kmt2b", "the kmt2a and kmt2b complexes", "kmt2a and kmt2b complexes preferentially", "and kmt2b complexes preferentially methylate", "kmt2b complexes preferentially methylate h3k4", "complexes preferentially methylate h3k4 at", "preferentially methylate h3k4 at a", "methylate h3k4 at a limited", "h3k4 at a limited number", "at a limited number of", "a limited number of target", "limited number of target gene", "number of target gene promoters", "target gene promoters while", "gene promoters while kmt2c", "promoters while kmt2c and", "while kmt2c and kmt2d complexes", "kmt2c and kmt2d complexes preferentially", "and kmt2d complexes preferentially methylate", "kmt2d complexes preferentially methylate h3k4", "number of target gene enhancers.", "of target gene enhancers. setd1a", "target gene enhancers. setd1a and", "gene enhancers. setd1a and setd1b", "enhancers. setd1a and setd1b complexes", "setd1a and setd1b complexes are", "and setd1b complexes are responsible", "setd1b complexes are responsible for", "complexes are responsible for the", "are responsible for the bulk", "responsible for the bulk of", "for the bulk of cellular", "the bulk of cellular h3k4", "bulk of cellular h3k4 methylation", "of cellular h3k4 methylation and", "cellular h3k4 methylation and show", "h3k4 methylation and show less", "methylation and show less target", "and show less target specificity.", "show less target specificity. for", "less target specificity. for overview", "specificity. for overview please", "for overview please refer", "please refer to patel et", "refer to patel et al.", "to patel et al. 2009", "et al. 2009 wang", "al. 2009 wang et", "2009 wang et al.", "et al. 2009 rao", "al. 2009 rao and", "2009 rao and dou", "rao and dou 2015.

              in both", "and dou 2015.

              in both drosophila", "dou 2015.

              in both drosophila and", "2015.

              in both drosophila and vertebrates", "drosophila and vertebrates kmt2", "and vertebrates kmt2 complexes", "vertebrates kmt2 complexes control", "kmt2 complexes control the expression", "complexes control the expression of", "control the expression of evolutionarily", "the expression of evolutionarily conserved", "expression of evolutionarily conserved hox", "of evolutionarily conserved hox genes", "evolutionarily conserved hox genes which", "conserved hox genes which serve", "hox genes which serve as", "genes which serve as master", "which serve as master regulators", "serve as master regulators of", "as master regulators of embryonic", "master regulators of embryonic patterning", "of embryonic patterning reviewed", "embryonic patterning reviewed in", "patterning reviewed in soshnikova", "reviewed in soshnikova and duboule", "in soshnikova and duboule 2009", "soshnikova and duboule 2009 .

              germline", "and duboule 2009 .

              germline mutations", "duboule 2009 .

              germline mutations in", "2009 .

              germline mutations in human", ".

              germline mutations in human kmt2", "mutations in human kmt2 complexes", "in human kmt2 complexes are", "human kmt2 complexes are the", "kmt2 complexes are the underlying", "complexes are the underlying cause", "are the underlying cause of", "the underlying cause of several", "underlying cause of several chromatinopathies.", "cause of several chromatinopathies. germline", "of several chromatinopathies. germline loss", "several chromatinopathies. germline loss of", "chromatinopathies. germline loss of function", "loss of function lof", "function lof mutations", "lof mutations in kmt2a", "mutations in kmt2a cause weideman", "in kmt2a cause weideman steiner", "kmt2a cause weideman steiner syndrome", "weideman steiner syndrome a", "steiner syndrome a rare", "syndrome a rare autosomal", "a rare autosomal dominant disorder", "rare autosomal dominant disorder characterized", "autosomal dominant disorder characterized by", "dominant disorder characterized by intellectual", "disorder characterized by intellectual disability", "by intellectual disability developmental", "intellectual disability developmental delay", "delay pre and", "pre and post natal", "and post natal growth delay", "natal growth delay hypertrichosis", "delay hypertrichosis short", "stature hypotonia distinctive", "hypotonia distinctive facial features", "distinctive facial features skeletal", "facial features skeletal abnormalities", "skeletal abnormalities feeding problems", "abnormalities feeding problems and", "feeding problems and behavioral difficulties", "and behavioral difficulties reviewed", "behavioral difficulties reviewed in", "difficulties reviewed in castiglioni", "reviewed in castiglioni et al.", "in castiglioni et al. 2022", "castiglioni et al. 2022 .", "et al. 2022 . germline", "al. 2022 . germline lof", "2022 . germline lof mutations", ". germline lof mutations in", "germline lof mutations in kmt2b", "lof mutations in kmt2b cause", "mutations in kmt2b cause dystonia", "in kmt2b cause dystonia 28", "cause dystonia 28 dyt28", "28 dyt28 and", "dyt28 and intellectual developmental", "and intellectual developmental autosomal", "intellectual developmental autosomal dominant", "developmental autosomal dominant disorder", "dominant disorder 68 mrd68", "disorder 68 mrd68 .", "68 mrd68 . dyt28", "mrd68 . dyt28 is an", ". dyt28 is an autosomal", "dyt28 is an autosomal dominant", "is an autosomal dominant neurologic", "an autosomal dominant neurologic disorder", "autosomal dominant neurologic disorder characterized", "dominant neurologic disorder characterized by", "neurologic disorder characterized by onset", "disorder characterized by onset of", "characterized by onset of progressive", "by onset of progressive dystonia", "onset of progressive dystonia in", "of progressive dystonia in the", "progressive dystonia in the first", "dystonia in the first decade", "in the first decade of", "the first decade of life", "decade of life reviewed", "of life reviewed in", "life reviewed in zech", "reviewed in zech et al.", "in zech et al. 2019", "al. 2019 while", "2019 while mrd68", "while mrd68 is an autosomal", "mrd68 is an autosomal dominant", "is an autosomal dominant disorder", "an autosomal dominant disorder characterized", "dominant disorder characterized by developmental", "disorder characterized by developmental delay/intellectual", "characterized by developmental delay/intellectual disability", "developmental delay/intellectual disability microcephaly", "disability microcephaly poor", "poor growth feeding difficulties", "feeding difficulties and dysmorphic", "difficulties and dysmorphic features", "and dysmorphic features cif", "dysmorphic features cif et", "features cif et al.", "cif et al. 2020 .", "et al. 2020 . germline", "al. 2020 . germline lof", "2020 . germline lof mutations", "germline lof mutations in kmt2c", "lof mutations in kmt2c cause", "mutations in kmt2c cause kleefstra", "in kmt2c cause kleefstra syndrome", "kmt2c cause kleefstra syndrome 2", "kleefstra syndrome 2 klefs2", "klefs2 an autosomal", "an autosomal dominant neurodevelopmental disorder", "autosomal dominant neurodevelopmental disorder characterized", "dominant neurodevelopmental disorder characterized by", "neurodevelopmental disorder characterized by delayed", "disorder characterized by delayed psychomotor", "characterized by delayed psychomotor development", "delayed psychomotor development variable", "psychomotor development variable intellectual", "development variable intellectual disability", "variable intellectual disability and", "intellectual disability and mild", "disability and mild dysmorphic", "mild dysmorphic features reviewed", "dysmorphic features reviewed in", "features reviewed in lavery", "reviewed in lavery et al.", "in lavery et al. 2020", "lavery et al. 2020 .", "germline lof mutations in kmt2d", "lof mutations in kmt2d cause", "mutations in kmt2d cause kabuki", "in kmt2d cause kabuki syndrome", "kmt2d cause kabuki syndrome 1", "kabuki syndrome 1 a", "syndrome 1 a congenital", "1 a congenital mental", "a congenital mental retardation syndrome", "congenital mental retardation syndrome with", "mental retardation syndrome with postnatal", "retardation syndrome with postnatal dwarfism", "with postnatal dwarfism a", "postnatal dwarfism a facial", "dwarfism a facial dysmorphism", "a facial dysmorphism and skeletal", "facial dysmorphism and skeletal abnormalities", "and skeletal abnormalities reviewed", "skeletal abnormalities reviewed in", "abnormalities reviewed in lavery", "germline lof mutations in setd1a", "lof mutations in setd1a cause", "mutations in setd1a cause early", "in setd1a cause early onset", "setd1a cause early onset epilepsy", "cause early onset epilepsy with", "early onset epilepsy with or", "onset epilepsy with or without", "epilepsy with or without developmental", "with or without developmental delay", "without developmental delay epedd", "epedd an autosomal", "dominant neurologic disorder yu", "neurologic disorder yu et", "disorder yu et al.", "al. 2019 and", "2019 and neurodevelopmental", "and neurodevelopmental disorder with speech", "neurodevelopmental disorder with speech impairment", "disorder with speech impairment and", "with speech impairment and dysmorphic", "speech impairment and dysmorphic facies", "and dysmorphic facies nedsid", "nedsid kummeling et", "kummeling et al. 2021 .", "et al. 2021 . germline", "al. 2021 . germline lof", "2021 . germline lof mutations", "germline lof mutations in setd1b", "lof mutations in setd1b cause", "mutations in setd1b cause intellectual", "in setd1b cause intellectual developmental", "setd1b cause intellectual developmental disorder", "cause intellectual developmental disorder with", "intellectual developmental disorder with seizures", "developmental disorder with seizures and", "disorder with seizures and language", "with seizures and language delay", "and language delay iddseld", "iddseld roston et", "roston et al. 2021 .

              somatic", "et al. 2021 .

              somatic mutations", "al. 2021 .

              somatic mutations in", "2021 .

              somatic mutations in kmt2", ".

              somatic mutations in kmt2 genes", "mutations in kmt2 genes contribute", "in kmt2 genes contribute to", "kmt2 genes contribute to cancer", "genes contribute to cancer development.", "contribute to cancer development. they", "to cancer development. they were", "cancer development. they were first", "development. they were first discovered", "they were first discovered in", "were first discovered in mixed", "first discovered in mixed lineage", "discovered in mixed lineage leukemia", "mll characterized by", "characterized by chromosomal translocations that", "by chromosomal translocations that involve", "chromosomal translocations that involve the", "translocations that involve the kmt2a", "that involve the kmt2a gene", "involve the kmt2a gene locus", "the kmt2a gene locus on", "kmt2a gene locus on chromosome", "gene locus on chromosome 11", "on chromosome 11 chromosomal", "chromosome 11 chromosomal band", "11 chromosomal band 11q23", "chromosomal band 11q23 and", "band 11q23 and result", "11q23 and result in", "and result in the expression", "result in the expression of", "in the expression of fusion", "the expression of fusion proteins", "expression of fusion proteins with", "of fusion proteins with oncogenic", "fusion proteins with oncogenic properties.", "proteins with oncogenic properties. besides", "with oncogenic properties. besides gene", "oncogenic properties. besides gene fusions", "besides gene fusions other", "gene fusions other types", "fusions other types of", "other types of kmt2a mutations", "types of kmt2a mutations are", "of kmt2a mutations are also", "kmt2a mutations are also present", "mutations are also present in", "are also present in blood", "also present in blood cancers", "in blood cancers most", "blood cancers most frequently", "cancers most frequently in", "most frequently in high grade", "frequently in high grade b", "in high grade b cell", "high grade b cell lymphoma", "b cell lymphoma t", "cell lymphoma t cell", "lymphoma t cell lymphoblastic", "cell lymphoblastic leukemia and", "lymphoblastic leukemia and acute", "leukemia and acute myeloid", "acute myeloid leukemia and", "myeloid leukemia and solid", "leukemia and solid tumors", "and solid tumors most", "solid tumors most often", "tumors most often reported", "most often reported in lung", "often reported in lung adenocarcinoma", "in lung adenocarcinoma colon", "lung adenocarcinoma colon adenocarcinoma", "colon adenocarcinoma and bladder", "adenocarcinoma and bladder urothelial", "and bladder urothelial carcinoma .", "bladder urothelial carcinoma . somatic", "urothelial carcinoma . somatic cancer", "carcinoma . somatic cancer mutations", ". somatic cancer mutations in", "somatic cancer mutations in other", "cancer mutations in other kmt2", "mutations in other kmt2 genes", "other kmt2 genes kmt2b", "genes kmt2b kmt2c", "kmt2d setd1a and setd1b", "setd1a and setd1b are", "and setd1b are less", "setd1b are less characterized", "are less characterized but most", "less characterized but most frequently", "characterized but most frequently affect", "but most frequently affect the", "most frequently affect the catalytic", "frequently affect the catalytic set", "affect the catalytic set domain", "the catalytic set domain and", "catalytic set domain and show", "set domain and show different", "domain and show different distributions", "and show different distributions between", "show different distributions between different", "different distributions between different cancer", "distributions between different cancer types.", "between different cancer types. for", "different cancer types. for review", "types. for review please", "to rao and dou 2015", "and dou 2015 castiglioni", "dou 2015 castiglioni et", "2015 castiglioni et al.", "castiglioni et al. 2022. several", "et al. 2022. several anti", "al. 2022. several anti cancer", "2022. several anti cancer therapeutics", "several anti cancer therapeutics are", "anti cancer therapeutics are being", "cancer therapeutics are being developed", "therapeutics are being developed that", "are being developed that affect", "being developed that affect the", "developed that affect the association", "that affect the association of", "affect the association of kmt2", "the association of kmt2 enzymes", "association of kmt2 enzymes with", "of kmt2 enzymes with components", "kmt2 enzymes with components of", "enzymes with components of the", "with components of the wrad", "components of the wrad complex", "the wrad complex in", "wrad complex in particular", "complex in particular wdr5", "in particular wdr5 reviewed", "particular wdr5 reviewed in", "wdr5 reviewed in vedadi", "reviewed in vedadi et al.", "in vedadi et al. 2017", "et al. 2017 siladi", "al. 2017 siladi et", "2017 siladi et al.", "siladi et al. 2022 .

              wdr5", "et al. 2022 .

              wdr5 is", "al. 2022 .

              wdr5 is also", "2022 .

              wdr5 is also a", ".

              wdr5 is also a component", "is also a component of", "also a component of three", "a component of three histone", "component of three histone acetyltransferase", "of three histone acetyltransferase complexes", "histone acetyltransferase complexes gcn5", "acetyltransferase complexes gcn5 atac", "gcn5 atac pcaf atac", "pcaf atac and mof/kat8", "atac and mof/kat8 nsl.", "and mof/kat8 nsl. the role", "mof/kat8 nsl. the role of", "nsl. the role of wdr5", "the role of wdr5 in", "role of wdr5 in epigenetic", "of wdr5 in epigenetic regulation", "wdr5 in epigenetic regulation of", "in epigenetic regulation of gene", "epigenetic regulation of gene expression", "regulation of gene expression through", "of gene expression through histone", "gene expression through histone acetylation", "expression through histone acetylation is", "through histone acetylation is under", "histone acetylation is under investigation", "is under investigation reviewed", "under investigation reviewed in", "investigation reviewed in guarnaccia", "reviewed in guarnaccia and tansey", "in guarnaccia and tansey 2018", "guarnaccia and tansey 2018 .

              the", "and tansey 2018 .

              the function", "tansey 2018 .

              the function of", "2018 .

              the function of wdr5", ".

              the function of wdr5 containing", "function of wdr5 containing histone", "containing histone modifying complexes is", "histone modifying complexes is currently", "modifying complexes is currently depicted", "complexes is currently depicted in", "is currently depicted in the", "currently depicted in the following", "depicted in the following reactome", "in the following reactome pathways:", "the following reactome pathways: \\transcriptional", "following reactome pathways: \\transcriptional regulation", "reactome pathways: \\transcriptional regulation of", "pathways: \\transcriptional regulation of granulopoiesis\\", "regulation of granulopoiesis\\ mll1", "of granulopoiesis\\ mll1 complex", "mll1 complex \\transcriptional", "complex \\transcriptional regulation", "regulation by runx1\\ mll1", "by runx1\\ mll1 complex", "mll1 complex \\activation", "complex \\activation of", "\\activation of anterior hox genes", "of anterior hox genes in", "anterior hox genes in hindbrain", "hox genes in hindbrain development", "genes in hindbrain development during", "in hindbrain development during early", "hindbrain development during early embryogenesis\\", "during early embryogenesis\\ mll3", "early embryogenesis\\ mll3 complex", "embryogenesis\\ mll3 complex and", "mll3 complex and mll4 complex", "mll4 complex \\tcf", "complex \\tcf dependent", "\\tcf dependent signaling in response", "dependent signaling in response to", "signaling in response to wnt\\", "response to wnt\\ mll4", "to wnt\\ mll4 complex", "mll4 complex and", "complex and \\chromatin", "and \\chromatin organization\\ mll1", "\\chromatin organization\\ mll1 complex", "mll1 complex mll2 complex", "mll2 complex mll3 complex", "mll3 complex mll4 complex", "mll4 complex set1a complex", "set1a complex set1b complex", "set1b complex gcn5 atac", "complex gcn5 atac complex", "gcn5 atac complex pcaf", "atac complex pcaf atac", "complex pcaf atac complex", "pcaf atac complex and", "atac complex and mof/kat8", "complex and mof/kat8 nsl", "and mof/kat8 nsl complex .", "mof/kat8 nsl complex . please", "nsl complex . please note", "complex . please note that", ". please note that there", "please note that there is", "note that there is an", "that there is an inconsistency", "there is an inconsistency in", "is an inconsistency in naming", "an inconsistency in naming of", "inconsistency in naming of mll2", "in naming of mll2 and", "naming of mll2 and mll4", "of mll2 and mll4 complexes", "mll2 and mll4 complexes in", "and mll4 complexes in the", "mll4 complexes in the literature", "complexes in the literature and", "in the literature and in", "the literature and in reactome", "literature and in reactome pathways", "in reactome pathways as", "reactome pathways as mll2", "pathways as mll2 and", "as mll2 and mll4 have", "mll2 and mll4 have been", "and mll4 have been used", "mll4 have been used as", "have been used as synonyms", "been used as synonyms for", "used as synonyms for both", "as synonyms for both kmt2b", "synonyms for both kmt2b and", "for both kmt2b and kmt2d", "kmt2b and kmt2d depending", "and kmt2d depending on", "kmt2d depending on whether", "depending on whether the numbering", "on whether the numbering of", "whether the numbering of mlls", "the numbering of mlls referred", "numbering of mlls referred to", "of mlls referred to order", "mlls referred to order of", "referred to order of cloning", "to order of cloning or", "order of cloning or whether", "of cloning or whether it", "cloning or whether it referred", "or whether it referred to", "whether it referred to similarity", "it referred to similarity to", "referred to similarity to founding", "to similarity to founding mll1", "to founding mll1 mll", "mll1 mll kmt2a", "mll kmt2a enzyme.", "kmt2a enzyme. the current", "enzyme. the current uniprot standard", "the current uniprot standard is", "current uniprot standard is for", "uniprot standard is for mll2", "standard is for mll2 to", "is for mll2 to be", "for mll2 to be used", "mll2 to be used as", "to be used as the", "be used as the preferred", "used as the preferred synonym", "as the preferred synonym of", "the preferred synonym of kmt2b", "synonym of kmt2b and", "of kmt2b and for", "kmt2b and for mll4", "and for mll4 to be", "for mll4 to be used", "mll4 to be used as", "the preferred synonym of kmt2d." ] }, { "record_id": "GLY_000594_1_2053", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9752946", "r hsa", "hsa 9752946", "r hsa 9752946" ] }, { "record_id": "GLY_000594_1_2053", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "expression and", "and translocation", "translocation of", "of olfactory", "olfactory receptors", "expression and translocation", "and translocation of", "translocation of olfactory", "of olfactory receptors", "expression and translocation of", "and translocation of olfactory", "translocation of olfactory receptors", "expression 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              accumulation", "transcription.
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              most", ".
              most or", "or proteins", "proteins are", "are inefficiently", "inefficiently translocated", "translocated from", "from the", "membrane to", "the plasma", "plasma membrane", "membrane when", "when they", "they are", "are expressed", "expressed in", "in heterologous", "heterologous cells.", "cells. osns", "osns contain", "contain specific", "specific proteins", "proteins that", "that act", "act as", "as chaperones", "chaperones to", "to increase", "increase subcellular", "subcellular translocation", "of at", "at least", "least some", "some ors", "in mainland", "mainland and", "and matsunami", "matsunami 2012", "2012 .", "the short", "short isoform", "isoform of", "of rtp1", "and rtp2", "rtp2 bind", "bind the", "the or", "or in", "are translocated", "translocated with", "or to", "and remain", "remain at", "at the", "plasma membrane.", "membrane. reep1", "reep1 more", "more weakly", "weakly increases", "increases translocation", "of ors", "ors by", "an uncharacterized", "uncharacterized mechanism.", "receptors ors", "are 7 pass", "7 pass transmembrane", "pass transmembrane g", "transmembrane g protein", "g protein coupled", "protein coupled receptors", "receptors gpcrs", "gpcrs located", "located on dendritic", "on dendritic cilia", "dendritic cilia of", "cilia of olfactory", "of olfactory sensory", "olfactory sensory neurons", "neurons osns", "osns of", "of the olfactory", "the olfactory epithelium", "epithelium reviewed", "reviewed in persuy", "in persuy et", "persuy et al.", "et al. 2015", "al. 2015 .", "2015 . ors", ". ors are", "ors are also", "are also located", "also located on", "located on cells", "on cells of", "cells of some", "of some other", "some other tissues", "tissues reviewed", "reviewed in oh", "in oh 2015", "oh 2015 .", ". ors bind", "ors bind ligands", "ligands called", "odorants and", "and activate downstream", "activate downstream signaling", "downstream signaling through", "signaling through a", "through a heterotrimeric", "a heterotrimeric g", "heterotrimeric g protein", "g protein leading", "protein leading to", "leading to opening", "to opening of", "opening of olfactory", "of olfactory cyclic", "olfactory cyclic nucleotide", "cyclic nucleotide gated", "nucleotide gated channels", "channels cng", "channels and", "and depolarization of", "depolarization of the", "of the osn.", "the osn. the", "osn. the human", "the human genome", "human genome contains", "genome contains about", "contains about 857", "about 857 or", "857 or genes", "or genes of", "genes of which", "of which about", "which about 394", "about 394 appear", "394 appear to", "appear to be", "to be capable", "be capable of", "capable of encoding", "of encoding a", "encoding a functional", "a functional or.", "functional or. the", "or. the remaining", "the remaining putative", "remaining putative or", "putative or genes", "or genes appear", "genes appear to", "to be pseudogenes", "be pseudogenes functionally", "pseudogenes functionally inactivated", "functionally inactivated by", "inactivated by mutations.
              each", "by mutations.
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              most", "2013 .
              most or", ".
              most or proteins", "or proteins are", "proteins are inefficiently", "are inefficiently translocated", "inefficiently translocated from", "translocated from the", "from the endoplasmic", "reticulum membrane to", "membrane to the", "to the plasma", "the plasma membrane", "plasma membrane when", "membrane when they", "when they are", "they are expressed", "are expressed in", "expressed in heterologous", "in heterologous cells.", "heterologous cells. osns", "cells. osns contain", "osns contain specific", "contain specific proteins", "specific proteins that", "proteins that act", "that act as", "act as chaperones", "as chaperones to", "chaperones to increase", "to increase subcellular", "increase subcellular translocation", "subcellular translocation of", "translocation of at", "of at least", "at least some", "least some ors", "ors reviewed", "reviewed in mainland", "in mainland and", "mainland and matsunami", "and matsunami 2012", "matsunami 2012 .", "2012 . the", ". the short", "the short isoform", "short isoform of", "isoform of rtp1", "rtp1 rtp1s", "rtp1s and", "and rtp2 bind", "rtp2 bind the", "bind the or", "the or in", "or in the", "reticulum are", "are translocated with", "translocated with the", "with the or", "the or to", "or to the", "membrane and", "and remain at", "remain at the", "at the plasma", "the plasma membrane.", "plasma membrane. reep1", "membrane. reep1 more", "reep1 more weakly", "more weakly increases", "weakly increases translocation", "increases translocation of", "translocation of ors", "of ors by", "ors by an", "by an uncharacterized", "an uncharacterized mechanism.", "olfactory receptors ors", "ors are 7", "are 7 pass transmembrane", "7 pass transmembrane g", "pass transmembrane g protein", "transmembrane g protein coupled", "g protein coupled receptors", "coupled receptors gpcrs", "gpcrs located on", "located on dendritic cilia", "on dendritic cilia of", "dendritic cilia of olfactory", "cilia of olfactory sensory", "of olfactory sensory neurons", "sensory neurons osns", "osns of the", "of the olfactory epithelium", "olfactory epithelium reviewed", "epithelium reviewed in", "reviewed in persuy et", "in persuy et al.", "persuy et al. 2015", "et al. 2015 .", "al. 2015 . ors", "2015 . ors are", ". ors are also", "ors are also located", "are also located on", "also located on cells", "located on cells of", "on cells of some", "cells of some other", "of some other tissues", "other tissues reviewed", "tissues reviewed in", "reviewed in oh 2015", "in oh 2015 .", "oh 2015 . ors", "2015 . ors bind", ". ors bind ligands", "bind ligands called", "ligands called odorants", "called odorants and", "odorants and activate", "and activate downstream signaling", "activate downstream signaling through", "downstream signaling through a", "signaling through a heterotrimeric", "through a heterotrimeric g", "a heterotrimeric g protein", "heterotrimeric g protein leading", "g protein leading to", "protein leading to opening", "leading to opening of", "to opening of olfactory", "opening of olfactory cyclic", "of olfactory cyclic nucleotide", "olfactory cyclic nucleotide gated", "cyclic nucleotide gated channels", "gated channels cng", "channels cng channels", "cng channels and", "channels and depolarization", "and depolarization of the", "depolarization of the osn.", "of the osn. the", "the osn. the human", "osn. the human genome", "the human genome contains", "human genome contains about", "genome contains about 857", "contains about 857 or", "about 857 or genes", "857 or genes of", "or genes of which", "genes of which about", "of which about 394", "which about 394 appear", "about 394 appear to", "394 appear to be", "appear to be capable", "to be capable of", "be capable of encoding", "capable of encoding a", "of encoding a functional", "encoding a functional or.", "a functional or. the", "functional or. the remaining", "or. the remaining putative", "the remaining putative or", "remaining putative or genes", "putative or genes appear", "or genes appear to", "genes appear to be", "appear to be pseudogenes", "to be pseudogenes functionally", "be pseudogenes functionally inactivated", "pseudogenes functionally inactivated by", "functionally inactivated by mutations.
              each", "inactivated by mutations.
              each or", "by mutations.
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              accumulation", "and drives transcription.
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              accumulation of or", "transcription.
              accumulation of or protein", "of or protein in", "or protein in the", "protein in the endoplasmic", "in the endoplasmic reticulum", "the endoplasmic reticulum membrane", "endoplasmic reticulum membrane activates", "reticulum membrane activates the", "membrane activates the unfolded", "activates the unfolded protein", "the unfolded protein response", "protein response upr", "upr that activates", "that activates translation of", "activates translation of adcy3", "of adcy3 which", "adcy3 which downregulates", "which downregulates the histone", "downregulates the histone methyltransferase", "the histone methyltransferase kdm1a", "methyltransferase kdm1a lsd1", "lsd1 thereby preventing", "thereby preventing activation of", "preventing activation of any", "activation of any other", "of any other or", "any other or genes", "or genes lyons", "genes lyons et", "lyons et al. 2013", "al. 2013 dalton", "2013 dalton et", "dalton et al. 2013", "et al. 2013 .
              most", "al. 2013 .
              most or", "2013 .
              most or proteins", ".
              most or proteins are", "or proteins are inefficiently", "proteins are inefficiently translocated", "are inefficiently translocated from", "inefficiently translocated from the", "translocated from the endoplasmic", "from the endoplasmic reticulum", "endoplasmic reticulum membrane to", "reticulum membrane to the", "membrane to the plasma", "to the plasma membrane", "the plasma membrane when", "plasma membrane when they", "membrane when they are", "when they are expressed", "they are expressed in", "are expressed in heterologous", "expressed in heterologous cells.", "in heterologous cells. osns", "heterologous cells. osns contain", "cells. osns contain specific", "osns contain specific proteins", "contain specific proteins that", "specific proteins that act", "proteins that act as", "that act as chaperones", "act as chaperones to", "as chaperones to increase", "chaperones to increase subcellular", "to increase subcellular translocation", "increase subcellular translocation of", "subcellular translocation of at", "translocation of at least", "of at least some", "at least some ors", "some ors reviewed", "ors reviewed in", "reviewed in mainland and", "in mainland and matsunami", "mainland and matsunami 2012", "and matsunami 2012 .", "matsunami 2012 . the", "2012 . the short", ". the short isoform", "the short isoform of", "short isoform of rtp1", "of rtp1 rtp1s", "rtp1s and rtp2", "and rtp2 bind the", "rtp2 bind the or", "bind the or in", "the or in the", "or in the endoplasmic", "endoplasmic reticulum are", "reticulum are translocated", "are translocated with the", "translocated with the or", "with the or to", "the or to the", "or to the plasma", "plasma membrane and", "membrane and remain", "and remain at the", "remain at the plasma", "at the plasma membrane.", "the plasma membrane. reep1", "plasma membrane. reep1 more", "membrane. reep1 more weakly", "reep1 more weakly increases", "more weakly increases translocation", "weakly increases translocation of", "increases translocation of ors", "translocation of ors by", "of ors by an", "ors by an uncharacterized", "by an uncharacterized mechanism.", "receptors ors are", "ors are 7 pass", "are 7 pass transmembrane g", "7 pass transmembrane g protein", "pass transmembrane g protein coupled", "transmembrane g protein coupled receptors", "protein coupled receptors gpcrs", "receptors gpcrs located", "gpcrs located on dendritic", "located on dendritic cilia of", "on dendritic cilia of olfactory", "dendritic cilia of olfactory sensory", "cilia of olfactory sensory neurons", "olfactory sensory neurons osns", "neurons osns of", "osns of the olfactory", "the olfactory epithelium reviewed", "olfactory epithelium reviewed in", "epithelium reviewed in persuy", "reviewed in persuy et al.", "in persuy et al. 2015", "persuy et al. 2015 .", "et al. 2015 . ors", "al. 2015 . ors are", "2015 . ors are also", ". ors are also located", "ors are also located on", "are also located on cells", "also located on cells of", "located on cells of some", "on cells of some other", "cells of some other tissues", "some other tissues reviewed", "other tissues reviewed in", "tissues reviewed in oh", "reviewed in oh 2015 .", "in oh 2015 . ors", "oh 2015 . ors bind", "2015 . ors bind ligands", "ors bind ligands called", "bind ligands called odorants", "called odorants and activate", "odorants and activate downstream", "and activate downstream signaling through", "activate downstream signaling through a", "downstream signaling through a heterotrimeric", "signaling through a heterotrimeric g", "through a heterotrimeric g protein", "a heterotrimeric g protein leading", "heterotrimeric g protein leading to", "g protein leading to opening", "protein leading to opening of", "leading to opening of olfactory", "to opening of olfactory cyclic", "opening of olfactory cyclic nucleotide", "of olfactory cyclic nucleotide gated", "olfactory cyclic nucleotide gated channels", "nucleotide gated channels cng", "gated channels cng channels", "cng channels and depolarization", "channels and depolarization of", "and depolarization of the osn.", "depolarization of the osn. the", "of the osn. the human", "the osn. the human genome", "osn. the human genome contains", "the human genome contains about", "human genome contains about 857", "genome contains about 857 or", "contains about 857 or genes", "about 857 or genes of", "857 or genes of which", "or genes of which about", "genes of which about 394", "of which about 394 appear", "which about 394 appear to", "about 394 appear to be", "394 appear to be capable", "appear to be capable of", "to be capable of encoding", "be capable of encoding a", "capable of encoding a functional", "of encoding a functional or.", "encoding a functional or. the", "a functional or. the remaining", "functional or. the remaining putative", "or. the remaining putative or", "the remaining putative or genes", "remaining putative or genes appear", "putative or genes appear to", "or genes appear to be", "genes appear to be pseudogenes", "appear to be pseudogenes functionally", "to be pseudogenes functionally inactivated", "be pseudogenes functionally inactivated by", "pseudogenes functionally inactivated by mutations.
              each", "functionally inactivated by mutations.
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              accumulation", "gene and drives transcription.
              accumulation of", "and drives transcription.
              accumulation of or", "drives transcription.
              accumulation of or protein", "transcription.
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              most", "et al. 2013 .
              most or", "al. 2013 .
              most or proteins", "2013 .
              most or proteins are", ".
              most or proteins are inefficiently", "or proteins are inefficiently translocated", "proteins are inefficiently translocated from", "are inefficiently translocated from the", "inefficiently translocated from the endoplasmic", "translocated from the endoplasmic reticulum", "from the endoplasmic reticulum membrane", "the endoplasmic reticulum membrane to", "endoplasmic reticulum membrane to the", "reticulum membrane to the plasma", "membrane to the plasma membrane", "to the plasma membrane when", "the plasma membrane when they", "plasma membrane when they are", "membrane when they are expressed", "when they are expressed in", "they are expressed in heterologous", "are expressed in heterologous cells.", "expressed in heterologous cells. osns", "in heterologous cells. osns contain", "heterologous cells. osns contain specific", "cells. osns contain specific proteins", "osns contain specific proteins that", "contain specific proteins that act", "specific proteins that act as", "proteins that act as chaperones", "that act as chaperones to", "act as chaperones to increase", "as chaperones to increase subcellular", "chaperones to increase subcellular translocation", "to increase subcellular translocation of", "increase subcellular translocation of at", "subcellular translocation of at least", "translocation of at least some", "of at least some ors", "least some ors reviewed", "some ors reviewed in", "ors reviewed in mainland", "reviewed in mainland and matsunami", "in mainland and matsunami 2012", "mainland and matsunami 2012 .", "and matsunami 2012 . the", "matsunami 2012 . the short", "2012 . the short isoform", ". the short isoform of", "the short isoform of rtp1", "isoform of rtp1 rtp1s", "rtp1 rtp1s and", "rtp1s and rtp2 bind", "and rtp2 bind the or", "rtp2 bind the or in", "bind the or in the", "the or in the endoplasmic", "or in the endoplasmic reticulum", "the endoplasmic reticulum are", "endoplasmic reticulum are translocated", "reticulum are translocated with", "are translocated with the or", "translocated with the or to", "with the or to the", "the or to the plasma", "or to the plasma membrane", "the plasma membrane and", "plasma membrane and remain", "membrane and remain at", "and remain at the plasma", "remain at the plasma membrane.", "at the plasma membrane. reep1", "the plasma membrane. reep1 more", "plasma membrane. reep1 more weakly", "membrane. reep1 more weakly increases", "reep1 more weakly increases translocation", "more weakly increases translocation of", "weakly increases translocation of ors", "increases translocation of ors by", "translocation of ors by an", "of ors by an uncharacterized", "ors by an uncharacterized mechanism." ] }, { "record_id": "GLY_000594_1_2054", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9754678", "r hsa", "hsa 9754678", "r hsa 9754678" ] }, { "record_id": "GLY_000594_1_2054", "filename": "human_protein_pathways_reactome", 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              the", ".
              the pik3r1", "regulatory subunit", "subunit of", "of phosphatidylinositol", "phosphatidylinositol 3", "3 kinase", "binds phosphotyrosine", "phosphotyrosine 723", "723 of", "phosphorylated src", "src binds", "phosphotyrosine 561", "561 of", "phosphorylated cbl", "cbl binds", "binds csf1r", "csf1r associated", "associated with", "with shc", "and grb2:sos", "grb2:sos binds", "saleem et", "al. 1995", "resulting activation", "activation of", "of the", "the catalytic", "catalytic subunit", "of pi3k", "pik2ca b", "b g", "produces phosphatidylinositol", "3 4", "4 5", "5 trisphosphate", "trisphosphate which", "which recruits", "recruits effectors", "effectors containing", "containing pleckstrin", "pleckstrin homology", "homology domains", "ph domains", "such as", "as pkb", "called akt", "to the", "the plasma", "plasma membrane.", "membrane. pathways", "pathways activated", "activated by", "by pi3k", "pi3k appear", "appear to", "to both", "both enhance", "enhance proliferation", "and migration", "migration of", "in dwyer", "via induction", "induction of", "of mir21", "suppress the", "the inflammatory", "inflammatory response", "response by", "by targeting", "targeting mrnas", "mrnas encoding", "encoding multiple", "multiple proinflammatory", "proinflammatory molecules.
              phospholipase", "molecules.
              phospholipase c", "c gamma2", "hydrolyzes phosphatidylcholine", "phosphatidylcholine to", "to yield", "yield choline", "choline phosphate", "and diacylglycerol", "and promotes", "promotes survival", "survival and", "macrophages via", "via pkcdelta", "homologs .
              grb2", ".
              grb2 bound", "bound to", "to sos1", "transiently interacts", "interacts with", "with phosphotyrosine", "phosphotyrosine 699", "699 of", "of csf1r.", "csf1r. sos1", "sos1 promotes", "promotes the", "the exchange", "exchange of", "of gdp", "gdp for", "for gtp", "gtp by", "by kras", "activating the", "the ras", "ras raf", "raf erk1", "erk1 2", "2 pathway", "pathway that", "that causes", "causes proliferation", "proliferation of", "of macrophage", "macrophage precursors", ". cbl", "cbl transiently", "transiently associates", "associates with", "with and", "and ubiquitinates", "ubiquitinates the", "the csf1r", "then is", "is deubiquitinated", "deubiquitinated and", "and returned", "returned to", "the cytoplasm", "homologs .
              phosphorylated", ".
              phosphorylated csf1r", "csf1r also", "also recruits", "recruits stat1", "stat1 and", "and stat3", "which are", "are then", "then phosphorylated", "the role", "role of", "of phosphorylated", "phosphorylated stat1", "stat1 3", "3 in", "in signaling", "by csf1r", "csf1r is", "is incompletely", "incompletely characterized.
              ", "characterized.
              csf1r", "a target", "target for", "for therapeutics", "as imatinib", "in kumari", "kumari et", "al. 2018", "2018 .", "colony stimulating factor", "stimulating factor 1", "1 csf1", "csf1 csf", "1 also", "also called macrophage", "called macrophage colony", "macrophage colony stimulating", "factor m", "csf is", "is a disulfide", "a disulfide linked", "disulfide linked dimer", "linked dimer that", "dimer that stimulates", "that stimulates the", "stimulates the proliferation", "the proliferation and", "proliferation and differentiation", "and differentiation of", "differentiation of mononuclear", "of mononuclear phagocytes", "mononuclear phagocytes and", "phagocytes and the", "and the survival", "survival proliferation", "proliferation motility", "motility and", "and anti inflammatory", "anti inflammatory activity", "inflammatory activity of", "activity of macrophages", "macrophages reviewed", "reviewed in mouchemore", "in mouchemore et", "mouchemore et al.", "et al. 2012", "2012 stanley", "stanley and chitu", "and chitu 2014", "2014 ushach", "ushach and zlotnik", "and zlotnik 2016", "2016 dwyer", "dwyer et al.", "et al. 2017", "al. 2017 and", "2017 and inferred", "and inferred from", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in caescu", "in caescu et", "caescu et al.", "et al. 2015", "al. 2015 .", "2015 . the", ". the unliganded", "the unliganded csf1", "unliganded csf1 receptor", "receptor csf1r", "csf1r csf", "1r is", "is either clustered", "either clustered or", "clustered or undergoing", "or undergoing rapid", "undergoing rapid dimer", "rapid dimer monomer", "dimer monomer transitions", "monomer transitions at", "transitions at the", "at the cell", "the cell surface", "surface li", "li and stanley", "and stanley 1991", "stanley 1991 .", "1991 . the", ". the csf1", "the csf1 dimer", "csf1 dimer initially", "dimer initially binds", "initially binds the", "binds the d2", "the d2 and", "d2 and d3", "and d3 extracellular", "d3 extracellular domains", "extracellular domains of", "domains of a", "of a monomer", "a monomer of", "monomer of csf1r", "csf1r wang", "wang et al.", "et al. 1993", "1993 chihara", "chihara et al.", "et al. 2010", "2010 ma", "ma et al.", "2012 felix", "felix et al.", "2015 and", "mouse homologs .", "homologs . a", ". a second", "a second monomer", "second monomer of", "of csf1r then", "csf1r then binds", "then binds the", "binds the csf1:csf1r", "the csf1:csf1r complex", "csf1:csf1r complex and", "complex and the", "and the resulting", "the resulting dimerization", "resulting dimerization of", "dimerization of csf1r", "of csf1r activates", "csf1r activates its", "activates its kinase", "its kinase activity", "activity elegheert", "elegheert et al.", "et al. 2011", "2011 felix", "homologs . csf1r", ". csf1r initially", "csf1r initially trans", "initially trans autophosphorylates", "trans autophosphorylates tyrosine", "autophosphorylates tyrosine 561", "tyrosine 561 in", "561 in the", "in the juxtamembrane", "the juxtamembrane domain", "domain relieving", "relieving negative autoinhibition", "negative autoinhibition of", "autoinhibition of kinase", "of kinase activity", "activity resulting", "resulting in the", "in the trans", "the trans autophosphorylation", "trans autophosphorylation of", "autophosphorylation of 7", "of 7 more", "7 more tyrosine", "more tyrosine residues", "tyrosine residues in", "residues in its", "in its cytoplasmic", "its cytoplasmic domain", "domain rohrschneider", "rohrschneider et al.", "et al. 1997", "1997 chihara", "2010 and", "homologs in xiong", "in xiong et", "xiong et al.", "al. 2011 .
              the", "2011 .
              the pik3r1", "pik3r1 p85alpha", "p85alpha regulatory", "regulatory subunit of", "subunit of phosphatidylinositol", "of phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "kinase pi3k", "pi3k binds", "binds phosphotyrosine 723", "phosphotyrosine 723 of", "723 of csf1r", "csf1r phosphorylated", "phosphorylated src binds", "src binds phosphotyrosine", "binds phosphotyrosine 561", "phosphotyrosine 561 of", "561 of csf1r", "phosphorylated cbl binds", "cbl binds csf1r", "binds csf1r associated", "csf1r associated with", "associated with shc", "shc and", "and grb2:sos binds", "grb2:sos binds csf1r", "csf1r saleem", "saleem et al.", "et al. 1995", "1995 and", "homologs . the", ". the resulting", "the resulting activation", "resulting activation of", "activation of the", "of the catalytic", "the catalytic subunit", "catalytic subunit of", "subunit of pi3k", "pi3k pik2ca", "pik2ca b g", "g produces", "produces phosphatidylinositol 3", "phosphatidylinositol 3 4", "3 4 5", "4 5 trisphosphate", "5 trisphosphate which", "trisphosphate which recruits", "which recruits effectors", "recruits effectors containing", "effectors containing pleckstrin", "containing pleckstrin homology", "pleckstrin homology domains", "domains ph", "domains such", "such as pkb", "pkb also", "also called akt", "akt to", "to the plasma", "the plasma membrane.", "plasma membrane. pathways", "membrane. pathways activated", "pathways activated by", "activated by pi3k", "by pi3k appear", "pi3k appear to", "appear to both", "to both enhance", "both enhance proliferation", "proliferation survival", "and migration of", "migration of macrophages", "reviewed in dwyer", "in dwyer et", "and via", "via induction of", "induction of mir21", "mir21 suppress", "suppress the inflammatory", "the inflammatory response", "inflammatory response by", "response by targeting", "by targeting mrnas", "targeting mrnas encoding", "mrnas encoding multiple", "encoding multiple proinflammatory", "multiple proinflammatory molecules.
              phospholipase", "proinflammatory molecules.
              phospholipase c", "molecules.
              phospholipase c gamma2", "gamma2 plcg2", "plcg2 binds", "csf1r hydrolyzes", "hydrolyzes phosphatidylcholine to", "phosphatidylcholine to yield", "to yield choline", "yield choline phosphate", "phosphate phosphocholine", "phosphocholine and", "diacylglycerol and", "and promotes survival", "promotes survival and", "survival and differentiation", "differentiation of macrophages", "of macrophages via", "macrophages via pkcdelta", "pkcdelta prkcd", "mouse homologs .
              grb2", "homologs .
              grb2 bound", ".
              grb2 bound to", "bound to sos1", "sos1 grb2:sos1", "grb2:sos1 transiently", "transiently interacts with", "interacts with phosphotyrosine", "with phosphotyrosine 699", "phosphotyrosine 699 of", "699 of csf1r.", "of csf1r. sos1", "csf1r. sos1 promotes", "sos1 promotes the", "promotes the exchange", "the exchange of", "exchange of gdp", "of gdp for", "gdp for gtp", "for gtp by", "gtp by kras", "kras activating", "activating the ras", "the ras raf", "ras raf erk1", "raf erk1 2", "erk1 2 pathway", "2 pathway that", "pathway that causes", "that causes proliferation", "causes proliferation of", "proliferation of macrophage", "of macrophage precursors", "precursors inferred", "homologs . cbl", ". cbl transiently", "cbl transiently associates", "transiently associates with", "associates with and", "with and ubiquitinates", "and ubiquitinates the", "ubiquitinates the csf1r", "then is deubiquitinated", "is deubiquitinated and", "deubiquitinated and returned", "and returned to", "returned to the", "to the cytoplasm", "cytoplasm inferred", "mouse homologs .
              phosphorylated", "homologs .
              phosphorylated csf1r", ".
              phosphorylated csf1r also", "csf1r also recruits", "also recruits stat1", "recruits stat1 and", "stat1 and stat3", "stat3 which", "which are then", "are then phosphorylated", "phosphorylated inferred", ". the role", "the role of", "role of phosphorylated", "of phosphorylated stat1", "phosphorylated stat1 3", "stat1 3 in", "3 in signaling", "in signaling by", "signaling by csf1r", "by csf1r is", "csf1r is incompletely", "is incompletely characterized.
              ", "incompletely characterized.
              csf1r", "characterized.
              csf1r is", "csf1r is a", "is a target", "a target for", "target for therapeutics", "therapeutics such", "such as imatinib", "imatinib reviewed", "reviewed in kumari", "in kumari et", "kumari et al.", "et al. 2018", "al. 2018 .", "colony stimulating factor 1", "factor 1 csf1", "csf1 csf 1", "csf 1 also", "1 also called", "also called macrophage colony", "called macrophage colony stimulating", "macrophage colony stimulating factor", "stimulating factor m", "factor m csf", "m csf is", "csf is a", "is a disulfide linked", "a disulfide linked dimer", "disulfide linked dimer that", "linked dimer that stimulates", "dimer that stimulates the", "that stimulates the proliferation", "stimulates the proliferation and", "the proliferation and differentiation", "proliferation and differentiation of", "and differentiation of mononuclear", "differentiation of mononuclear phagocytes", "of mononuclear phagocytes and", "mononuclear phagocytes and the", "phagocytes and the survival", "the survival proliferation", "motility and anti", "and anti inflammatory activity", "anti inflammatory activity of", "inflammatory activity of macrophages", "of macrophages reviewed", "macrophages reviewed in", "reviewed in mouchemore et", "in mouchemore et al.", "mouchemore et al. 2012", "al. 2012 stanley", "2012 stanley and", "stanley and chitu 2014", "chitu 2014 ushach", "2014 ushach and", "ushach and zlotnik 2016", "zlotnik 2016 dwyer", "2016 dwyer et", "dwyer et al. 2017", "et al. 2017 and", "al. 2017 and inferred", "2017 and inferred from", "and inferred from mouse", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in caescu", "homologs in caescu et", "in caescu et al.", "caescu et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the unliganded", ". the unliganded csf1", "the unliganded csf1 receptor", "csf1 receptor csf1r", "csf1r csf 1r", "csf 1r is", "1r is either", "is either clustered or", "either clustered or undergoing", "clustered or undergoing rapid", "or undergoing rapid dimer", "undergoing rapid dimer monomer", "rapid dimer monomer transitions", "dimer monomer transitions at", "monomer transitions at the", "transitions at the cell", "at the cell surface", "cell surface li", "surface li and", "li and stanley 1991", "and stanley 1991 .", "stanley 1991 . the", "1991 . the csf1", ". the csf1 dimer", "the csf1 dimer initially", "csf1 dimer initially binds", "dimer initially binds the", "initially binds the d2", "binds the d2 and", "the d2 and d3", "d2 and d3 extracellular", "and d3 extracellular domains", "d3 extracellular domains of", "extracellular domains of a", "domains of a monomer", "of a monomer of", "a monomer of csf1r", "of csf1r wang", "csf1r wang et", "wang et al. 1993", "al. 1993 chihara", "1993 chihara et", "chihara et al. 2010", "al. 2010 ma", "2010 ma et", "ma et al. 2012", "al. 2012 felix", "2012 felix et", "felix et al. 2015", "al. 2015 and", "2015 and inferred", "from mouse homologs .", "mouse homologs . a", "homologs . a second", ". a second monomer", "a second monomer of", "second monomer of csf1r", "monomer of csf1r then", "of csf1r then binds", "csf1r then binds the", "then binds the csf1:csf1r", "binds the csf1:csf1r complex", "the csf1:csf1r complex and", "csf1:csf1r complex and the", "complex and the resulting", "and the resulting dimerization", "the resulting dimerization of", "resulting dimerization of csf1r", "dimerization of csf1r activates", "of csf1r activates its", "csf1r activates its kinase", "activates its kinase activity", "kinase activity elegheert", "activity elegheert et", "elegheert et al. 2011", "al. 2011 felix", "2011 felix et", "mouse homologs . csf1r", "homologs . csf1r initially", ". csf1r initially trans", "csf1r initially trans autophosphorylates", "initially trans autophosphorylates tyrosine", "trans autophosphorylates tyrosine 561", "autophosphorylates tyrosine 561 in", "tyrosine 561 in the", "561 in the juxtamembrane", "in the juxtamembrane domain", "juxtamembrane domain relieving", "domain relieving negative", "relieving negative autoinhibition of", "negative autoinhibition of kinase", "autoinhibition of kinase activity", "kinase activity resulting", "activity resulting in", "resulting in the trans", "in the trans autophosphorylation", "the trans autophosphorylation of", "trans autophosphorylation of 7", "autophosphorylation of 7 more", "of 7 more tyrosine", "7 more tyrosine residues", "more tyrosine residues in", "tyrosine residues in its", "residues in its cytoplasmic", "in its cytoplasmic domain", "cytoplasmic domain rohrschneider", "domain rohrschneider et", "rohrschneider et al. 1997", "al. 1997 chihara", "1997 chihara et", "al. 2010 and", "2010 and inferred", "mouse homologs in xiong", "homologs in xiong et", "in xiong et al.", "xiong et al. 2011", "et al. 2011 .
              the", "al. 2011 .
              the pik3r1", ".
              the pik3r1 p85alpha", "p85alpha regulatory subunit", "regulatory subunit of phosphatidylinositol", "subunit of phosphatidylinositol 3", "of phosphatidylinositol 3 kinase", "3 kinase pi3k", "pi3k binds phosphotyrosine", "binds phosphotyrosine 723 of", "phosphotyrosine 723 of csf1r", "of csf1r phosphorylated", "csf1r phosphorylated src", "phosphorylated src binds phosphotyrosine", "src binds phosphotyrosine 561", "binds phosphotyrosine 561 of", "phosphotyrosine 561 of csf1r", "csf1r phosphorylated cbl", "phosphorylated cbl binds csf1r", "cbl binds csf1r associated", "binds csf1r associated with", "csf1r associated with shc", "with shc and", "shc and grb2:sos", "and grb2:sos binds csf1r", "binds csf1r saleem", "csf1r saleem et", "saleem et al. 1995", "al. 1995 and", "1995 and inferred", "mouse homologs . the", "homologs . the resulting", ". the resulting activation", "the resulting activation of", "resulting activation of the", "activation of the catalytic", "of the catalytic subunit", "the catalytic subunit of", "catalytic subunit of pi3k", "of pi3k pik2ca", "pi3k pik2ca b", "b g produces", "g produces phosphatidylinositol", "produces phosphatidylinositol 3 4", "phosphatidylinositol 3 4 5", "3 4 5 trisphosphate", "4 5 trisphosphate which", "5 trisphosphate which recruits", "trisphosphate which recruits effectors", "which recruits effectors containing", "recruits effectors containing pleckstrin", "effectors containing pleckstrin homology", "containing pleckstrin homology domains", "homology domains ph", "domains ph domains", "ph domains such", "domains such as", "as pkb also", "pkb also called", "called akt to", "akt to the", "to the plasma membrane.", "the plasma membrane. pathways", "plasma membrane. pathways activated", "membrane. pathways activated by", "pathways activated by pi3k", "activated by pi3k appear", "by pi3k appear to", "pi3k appear to both", "appear to both enhance", "to both enhance proliferation", "enhance proliferation survival", "survival and migration", "and migration of macrophages", "reviewed in dwyer et", "in dwyer et al.", "and via induction", "via induction of mir21", "of mir21 suppress", "mir21 suppress the", "suppress the inflammatory response", "the inflammatory response by", "inflammatory response by targeting", "response by targeting mrnas", "by targeting mrnas encoding", "targeting mrnas encoding multiple", "mrnas encoding multiple proinflammatory", "encoding multiple proinflammatory molecules.
              phospholipase", "multiple proinflammatory molecules.
              phospholipase c", "proinflammatory molecules.
              phospholipase c gamma2", "c gamma2 plcg2", "plcg2 binds phosphotyrosine", "of csf1r hydrolyzes", "csf1r hydrolyzes phosphatidylcholine", "hydrolyzes phosphatidylcholine to yield", "phosphatidylcholine to yield choline", "to yield choline phosphate", "choline phosphate phosphocholine", "phosphocholine and diacylglycerol", "and diacylglycerol and", "diacylglycerol and promotes", "and promotes survival and", "promotes survival and differentiation", "survival and differentiation of", "and differentiation of macrophages", "differentiation of macrophages via", "of macrophages via pkcdelta", "via pkcdelta prkcd", "prkcd inferred", "from mouse homologs .
              grb2", "mouse homologs .
              grb2 bound", "homologs .
              grb2 bound to", ".
              grb2 bound to sos1", "to sos1 grb2:sos1", "grb2:sos1 transiently interacts", "transiently interacts with phosphotyrosine", "interacts with phosphotyrosine 699", "with phosphotyrosine 699 of", "phosphotyrosine 699 of csf1r.", "699 of csf1r. sos1", "of csf1r. sos1 promotes", "csf1r. sos1 promotes the", "sos1 promotes the exchange", "promotes the exchange of", "the exchange of gdp", "exchange of gdp for", "of gdp for gtp", "gdp for gtp by", "for gtp by kras", "by kras activating", "kras activating the", "activating the ras raf", "the ras raf erk1", "ras raf erk1 2", "raf erk1 2 pathway", "erk1 2 pathway that", "2 pathway that causes", "pathway that causes proliferation", "that causes proliferation of", "causes proliferation of macrophage", "proliferation of macrophage precursors", "macrophage precursors inferred", "precursors inferred from", "mouse homologs . cbl", "homologs . cbl transiently", ". cbl transiently associates", "cbl transiently associates with", "transiently associates with and", "associates with and ubiquitinates", "with and ubiquitinates the", "and ubiquitinates the csf1r", "the csf1r then", "csf1r then is", "then is deubiquitinated and", "is deubiquitinated and returned", "deubiquitinated and returned to", "and returned to the", "returned to the cytoplasm", "the cytoplasm inferred", "cytoplasm inferred from", "from mouse homologs .
              phosphorylated", "mouse homologs .
              phosphorylated csf1r", "homologs .
              phosphorylated csf1r also", ".
              phosphorylated csf1r also recruits", "csf1r also recruits stat1", "also recruits stat1 and", "recruits stat1 and stat3", "and stat3 which", "stat3 which are", "which are then phosphorylated", "then phosphorylated inferred", "phosphorylated inferred from", "homologs . the role", ". the role of", "the role of phosphorylated", "role of phosphorylated stat1", "of phosphorylated stat1 3", "phosphorylated stat1 3 in", "stat1 3 in signaling", "3 in signaling by", "in signaling by csf1r", "signaling by csf1r is", "by csf1r is incompletely", "csf1r is incompletely characterized.
              ", "is incompletely characterized.
              csf1r", "incompletely characterized.
              csf1r is", "characterized.
              csf1r is a", "csf1r is a target", "is a target for", "a target for therapeutics", "for therapeutics such", "therapeutics such as", "as imatinib reviewed", "imatinib reviewed in", "reviewed in kumari et", "in kumari et al.", "kumari et al. 2018", "et al. 2018 .", "stimulating factor 1 csf1", "1 csf1 csf", "csf 1 also called", "1 also called macrophage", "also called macrophage colony stimulating", "called macrophage colony stimulating factor", "colony stimulating factor m", "stimulating factor m csf", "m csf is a", "csf is a disulfide", "is a disulfide linked dimer", "a disulfide linked dimer that", "disulfide linked dimer that stimulates", "linked dimer that stimulates the", "dimer that stimulates the proliferation", "that stimulates the proliferation and", "stimulates the proliferation and differentiation", "the proliferation and differentiation of", "proliferation and differentiation of mononuclear", "and differentiation of mononuclear phagocytes", "differentiation of mononuclear phagocytes and", "of mononuclear phagocytes and the", "mononuclear phagocytes and the survival", "and the survival proliferation", "survival proliferation motility", "proliferation motility and", "motility and anti inflammatory", "and anti inflammatory activity of", "anti inflammatory activity of macrophages", "activity of macrophages reviewed", "of macrophages reviewed in", "macrophages reviewed in mouchemore", "reviewed in mouchemore et al.", "in mouchemore et al. 2012", "et al. 2012 stanley", "al. 2012 stanley and", "2012 stanley and chitu", "and chitu 2014 ushach", "chitu 2014 ushach and", "2014 ushach and zlotnik", "and zlotnik 2016 dwyer", "zlotnik 2016 dwyer et", "2016 dwyer et al.", "dwyer et al. 2017 and", "et al. 2017 and inferred", "al. 2017 and inferred from", "2017 and inferred from mouse", "and inferred from mouse homologs", "inferred from mouse homologs in", "from mouse homologs in caescu", "mouse homologs in caescu et", "homologs in caescu et al.", "in caescu et al. 2015", "caescu et al. 2015 .", "et al. 2015 . the", "al. 2015 . the unliganded", "2015 . the unliganded csf1", ". the unliganded csf1 receptor", "unliganded csf1 receptor csf1r", "receptor csf1r csf", "csf 1r is either", "1r is either clustered", "is either clustered or undergoing", "either clustered or undergoing rapid", "clustered or undergoing rapid dimer", "or undergoing rapid dimer monomer", "undergoing rapid dimer monomer transitions", "rapid dimer monomer transitions at", "dimer monomer transitions at the", "monomer transitions at the cell", "transitions at the cell surface", "the cell surface li", "cell surface li and", "surface li and stanley", "li and stanley 1991 .", "and stanley 1991 . the", "stanley 1991 . the csf1", "1991 . the csf1 dimer", ". the csf1 dimer initially", "the csf1 dimer initially binds", "csf1 dimer initially binds the", "dimer initially binds the d2", "initially binds the d2 and", "binds the d2 and d3", "the d2 and d3 extracellular", "d2 and d3 extracellular domains", "and d3 extracellular domains of", "d3 extracellular domains of a", "extracellular domains of a monomer", "domains of a monomer of", "of a monomer of csf1r", "monomer of csf1r wang", "of csf1r wang et", "csf1r wang et al.", "et al. 1993 chihara", "al. 1993 chihara et", "1993 chihara et al.", "et al. 2010 ma", "al. 2010 ma et", "2010 ma et al.", "et al. 2012 felix", "al. 2012 felix et", "2012 felix et al.", "et al. 2015 and", "al. 2015 and inferred", "2015 and inferred from", "inferred from mouse homologs .", "from mouse homologs . a", "mouse homologs . a second", "homologs . a second monomer", ". a second monomer of", "a second monomer of csf1r", "second monomer of csf1r then", "monomer of csf1r then binds", "of csf1r then binds the", "csf1r then binds the csf1:csf1r", "then binds the csf1:csf1r complex", "binds the csf1:csf1r complex and", "the csf1:csf1r complex and the", "csf1:csf1r complex and the resulting", "complex and the resulting dimerization", "and the resulting dimerization of", "the resulting dimerization of csf1r", "resulting dimerization of csf1r activates", "dimerization of csf1r activates its", "of csf1r activates its kinase", "csf1r activates its kinase activity", "its kinase activity elegheert", "kinase activity elegheert et", "activity elegheert et al.", "et al. 2011 felix", "al. 2011 felix et", "2011 felix et al.", "from mouse homologs . csf1r", "mouse homologs . csf1r initially", "homologs . csf1r initially trans", ". csf1r initially trans autophosphorylates", "csf1r initially trans autophosphorylates tyrosine", "initially trans autophosphorylates tyrosine 561", "trans autophosphorylates tyrosine 561 in", "autophosphorylates tyrosine 561 in the", "tyrosine 561 in the juxtamembrane", "561 in the juxtamembrane domain", "the juxtamembrane domain relieving", "juxtamembrane domain relieving negative", "domain relieving negative autoinhibition", "relieving negative autoinhibition of kinase", "negative autoinhibition of kinase activity", "of kinase activity resulting", "kinase activity resulting in", "activity resulting in the", "resulting in the trans autophosphorylation", "in the trans autophosphorylation of", "the trans autophosphorylation of 7", "trans autophosphorylation of 7 more", "autophosphorylation of 7 more tyrosine", "of 7 more tyrosine residues", "7 more tyrosine residues in", "more tyrosine residues in its", "tyrosine residues in its cytoplasmic", "residues in its cytoplasmic domain", "its cytoplasmic domain rohrschneider", "cytoplasmic domain rohrschneider et", "domain rohrschneider et al.", "et al. 1997 chihara", "al. 1997 chihara et", "1997 chihara et al.", "et al. 2010 and", "al. 2010 and inferred", "2010 and inferred from", "from mouse homologs in xiong", "mouse homologs in xiong et", "homologs in xiong et al.", "in xiong et al. 2011", "xiong et al. 2011 .
              the", "et al. 2011 .
              the pik3r1", "2011 .
              the pik3r1 p85alpha", "pik3r1 p85alpha regulatory", "p85alpha regulatory subunit of", "regulatory subunit of phosphatidylinositol 3", "subunit of phosphatidylinositol 3 kinase", "phosphatidylinositol 3 kinase pi3k", "kinase pi3k binds", "pi3k binds phosphotyrosine 723", "binds phosphotyrosine 723 of csf1r", "723 of csf1r phosphorylated", "of csf1r phosphorylated src", "csf1r phosphorylated src binds", "phosphorylated src binds phosphotyrosine 561", "src binds phosphotyrosine 561 of", "binds phosphotyrosine 561 of csf1r", "561 of csf1r phosphorylated", "of csf1r phosphorylated cbl", "csf1r phosphorylated cbl binds", "phosphorylated cbl binds csf1r associated", "cbl binds csf1r associated with", "binds csf1r associated with shc", "associated with shc and", "with shc and grb2:sos", "shc and grb2:sos binds", "grb2:sos binds csf1r saleem", "binds csf1r saleem et", "csf1r saleem et al.", "et al. 1995 and", "al. 1995 and inferred", "1995 and inferred from", "from mouse homologs . the", "mouse homologs . the resulting", "homologs . the resulting activation", ". the resulting activation of", "the resulting activation of the", "resulting activation of the catalytic", "activation of the catalytic subunit", "of the catalytic subunit of", "the catalytic subunit of pi3k", "subunit of pi3k pik2ca", "of pi3k pik2ca b", "pi3k pik2ca b g", "pik2ca b g produces", "b g produces phosphatidylinositol", "g produces phosphatidylinositol 3", "produces phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "3 4 5 trisphosphate which", "4 5 trisphosphate which recruits", "5 trisphosphate which recruits effectors", "trisphosphate which recruits effectors containing", "which recruits effectors containing pleckstrin", "recruits effectors containing pleckstrin homology", "effectors containing pleckstrin homology domains", "pleckstrin homology domains ph", "homology domains ph domains", "ph domains such as", "domains such as pkb", "such as pkb also", "as pkb also called", "pkb also called akt", "also called akt to", "called akt to the", "akt to the plasma", "to the plasma membrane. pathways", "the plasma membrane. pathways activated", "plasma membrane. pathways activated by", "membrane. pathways activated by pi3k", "pathways activated by pi3k appear", "activated by pi3k appear to", "by pi3k appear to both", "pi3k appear to both enhance", "appear to both enhance proliferation", "both enhance proliferation survival", "proliferation survival and", "survival and migration of", "migration of macrophages reviewed", "macrophages reviewed in dwyer", "reviewed in dwyer et al.", "in dwyer et al. 2017", "2017 and via", "and via induction of", "induction of mir21 suppress", "of mir21 suppress the", "mir21 suppress the inflammatory", "suppress the inflammatory response by", "the inflammatory response by targeting", "inflammatory response by targeting mrnas", "response by targeting mrnas encoding", "by targeting mrnas encoding multiple", "targeting mrnas encoding multiple proinflammatory", "mrnas encoding multiple proinflammatory molecules.
              phospholipase", "encoding multiple proinflammatory molecules.
              phospholipase c", "multiple proinflammatory molecules.
              phospholipase c gamma2", "molecules.
              phospholipase c gamma2 plcg2", "gamma2 plcg2 binds", "plcg2 binds phosphotyrosine 723", "723 of csf1r hydrolyzes", "of csf1r hydrolyzes phosphatidylcholine", "csf1r hydrolyzes phosphatidylcholine to", "hydrolyzes phosphatidylcholine to yield choline", "phosphatidylcholine to yield choline phosphate", "yield choline phosphate phosphocholine", "phosphate phosphocholine and", "and diacylglycerol and promotes", "diacylglycerol and promotes survival", "and promotes survival and differentiation", "promotes survival and differentiation of", "survival and differentiation of macrophages", "and differentiation of macrophages via", "differentiation of macrophages via pkcdelta", "macrophages via pkcdelta prkcd", "prkcd inferred from", "inferred from mouse homologs .
              grb2", "from mouse homologs .
              grb2 bound", "mouse homologs .
              grb2 bound to", "homologs .
              grb2 bound to sos1", "bound to sos1 grb2:sos1", "sos1 grb2:sos1 transiently", "grb2:sos1 transiently interacts with", "transiently interacts with phosphotyrosine 699", "interacts with phosphotyrosine 699 of", "with phosphotyrosine 699 of csf1r.", "phosphotyrosine 699 of csf1r. sos1", "699 of csf1r. sos1 promotes", "of csf1r. sos1 promotes the", "csf1r. sos1 promotes the exchange", "sos1 promotes the exchange of", "promotes the exchange of gdp", "the exchange of gdp for", "exchange of gdp for gtp", "of gdp for gtp by", "gdp for gtp by kras", "gtp by kras activating", "by kras activating the", "kras activating the ras", "activating the ras raf erk1", "the ras raf erk1 2", "ras raf erk1 2 pathway", "raf erk1 2 pathway that", "erk1 2 pathway that causes", "2 pathway that causes proliferation", "pathway that causes proliferation of", "that causes proliferation of macrophage", "causes proliferation of macrophage precursors", "of macrophage precursors inferred", "macrophage precursors inferred from", "precursors inferred from mouse", "from mouse homologs . cbl", "mouse homologs . cbl transiently", "homologs . cbl transiently associates", ". cbl transiently associates with", "cbl transiently associates with and", "transiently associates with and ubiquitinates", "associates with and ubiquitinates the", "with and ubiquitinates the csf1r", "ubiquitinates the csf1r then", "the csf1r then is", "csf1r then is deubiquitinated", "then is deubiquitinated and returned", "is deubiquitinated and returned to", "deubiquitinated and returned to the", "and returned to the cytoplasm", "to the cytoplasm inferred", "the cytoplasm inferred from", "cytoplasm inferred from mouse", "inferred from mouse homologs .
              phosphorylated", "from mouse homologs .
              phosphorylated csf1r", "mouse homologs .
              phosphorylated csf1r also", "homologs .
              phosphorylated csf1r also recruits", ".
              phosphorylated csf1r also recruits stat1", "csf1r also recruits stat1 and", "also recruits stat1 and stat3", "stat1 and stat3 which", "and stat3 which are", "stat3 which are then", "are then phosphorylated inferred", "then phosphorylated inferred from", "phosphorylated inferred from mouse", "mouse homologs . the role", "homologs . the role of", ". the role of phosphorylated", "the role of phosphorylated stat1", "role of phosphorylated stat1 3", "of phosphorylated stat1 3 in", "phosphorylated stat1 3 in signaling", "stat1 3 in signaling by", "3 in signaling by csf1r", "in signaling by csf1r is", "signaling by csf1r is incompletely", "by csf1r is incompletely characterized.
              ", "csf1r is incompletely characterized.
              csf1r", "is incompletely characterized.
              csf1r is", "incompletely characterized.
              csf1r is a", "characterized.
              csf1r is a target", "csf1r is a target for", "is a target for therapeutics", "target for therapeutics such", "for therapeutics such as", "therapeutics such as imatinib", "such as imatinib reviewed", "as imatinib reviewed in", "imatinib reviewed in kumari", "reviewed in kumari et al.", "in kumari et al. 2018", "kumari et al. 2018 ." ] }, { "record_id": "GLY_000594_1_2062", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9692916", "r hsa", "hsa 9692916", "r hsa 9692916" ] }, { "record_id": "GLY_000594_1_2062", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 1", "1 activates/modulates", "activates/modulates innate", "innate immune", "immune responses", "sars cov 1", "cov 1 activates/modulates", "1 activates/modulates innate", "activates/modulates innate immune", "innate immune responses", "sars cov 1 activates/modulates", "cov 1 activates/modulates innate", "1 activates/modulates innate immune", "activates/modulates innate immune responses", "sars cov 1 activates/modulates innate", "cov 1 activates/modulates innate immune", "1 activates/modulates innate immune responses", "are positive", "positive sense", "sense rna", "rna viruses", "viruses that", "that replicate", "replicate in", "in the", "the interior", "interior of", "of double", "double membrane", "membrane vesicles", "the cytoplasm", "cytoplasm of", "of infected", "infected cells", "stertz s", "s et", "et al.", "al. 2007", "knoops k", "k et", "al. 2008", "2008 .", ". the", "the viral", "viral replication", "replication and", "and transcription", "transcription are", "are facilitated", "facilitated by", "by virus", "virus encoded", "encoded non", "non structural", "structural proteins", "1 nsp1\u2013nsp16", "that assemble", "assemble to", "to form", "form a", "a dmv", "dmv bound", "bound replication", "replication transcription", "transcription complex", "rtc .", "the replication", "replication strategy", "strategy of", "of covs", "covs can", "can generate", "generate both", "both single", "single stranded", "stranded rna", "and double", "double stranded", "that may", "may act", "act as", "as pathogen", "pathogen associated", "associated molecular", "molecular patterns", "recognized by", "by pattern", "pattern recognition", "recognition receptor", "such as", "as toll", "toll like", "like receptor", "receptor 7", "and tlr8", "antiviral innate", "immune response", "response receptor", "receptor rig", "rig i", "also known", "known as", "as dead", "dead box", "box protein", "protein 58", "and interferon", "interferon induced", "induced helicase", "helicase c", "c domain", "domain containing", "containing protein", "protein 1", "as mda5", "cervantes barragan", "barragan l", "l et", "chen y", "y et", "al. 2009", "daffis s", "al. 2010", "li y", "al. 2013", "2013 .", "the activated", "activated prrs", "prrs trigger", "trigger signaling", "signaling pathways", "pathways to", "to produce", "produce type", "type i", "i and", "and type", "type iii", "iii interferons", "interferons ifns", "ifns and", "and proinflammatory", "proinflammatory mediators", "mediators that", "that perform", "perform antiviral", "antiviral functions.", "functions. this", "this reactome", "reactome module", "module describes", "describes the", "the mechanisms", "mechanisms underlying", "underlying prr", "prr mediated", "mediated sensing", "sensing of", "of the", "the severe", "severe acute", "acute respiratory", "respiratory syndrome", "syndrome coronavirus", "coronavirus type", "type 1", "infection. first", "endosomal recognition", "recognition of", "of viral", "viral ssrna", "ssrna occurs", "occurs by", "by means", "means of", "of tlr7", "tlr7 and", "tlr8 which", "which detect", "detect gu", "gu rich", "rich ssrna", "ssrna sequences.", "sequences. specifically", "ssrna oligonucleotides", "oligonucleotides derived", "derived from", "from sars", "1 stimulated", "stimulated mononuclear", "mononuclear phagocytes", "phagocytes to", "to release", "release considerable", "considerable levels", "levels of", "of pro\u2011inflammatory", "pro\u2011inflammatory cytokines", "cytokines tnf\u2011a", "il\u20116 and", "and il\u201112", "il\u201112 via", "via tlr7", ". second", "1 dsrna", "dsrna replication", "replication intermediates", "intermediates can", "can be", "be recognized", "by cytoplasmic", "cytoplasmic receptors", "receptors ddx58", "ddx58 and", "and ifih1", "ifih1 which", "which bind", "bind to", "to mitochondrial", "mitochondrial antiviral", "antiviral signaling", "signaling protein", "ips 1", "to induce", "induce the", "the ifn", "ifn mediated", "mediated antiviral", "antiviral response.", "response. in", "in addition", "the module", "module shows", "shows an", "an antiviral", "antiviral function", "function of", "of interferon", "induced protein", "protein with", "with tetratricopeptide", "tetratricopeptide repeats", "repeats 1", "that directly", "directly binds", "binds and", "and sequesters", "sequesters viral", "viral single", "stranded uncapped", "uncapped 5\u2032", "5\u2032 ppp", "ppp rna", "rna and", "and cap", "cap 0", "0 rna", "2010 .", ". this", "this module", "module also", "also describes", "describes several", "several strategies", "strategies developed", "developed by", "by sars", "1 to", "to evade", "evade or", "or alter", "alter host", "host immunity", "including escaping", "escaping innate", "immune sensors", "inhibiting ifn", "ifn production", "production and", "and signaling", "and evading", "evading antiviral", "of ifn", "ifn stimulated", "stimulated gene", "products. for", "for example", "viral dsrna", "intermediates derived", "from sars\u2011cov\u20111", "sars\u2011cov\u20111 were", "were shown", "shown to", "to associate", "associate with", "with rtc", "rtc bound", "bound to", "to double", "which protected", "protected viral", "viral rna", "rna from", "from sensing", "sensing by", "by ddx58", "ddx58 or", "or ifih1", ". further", "1 encodes", "encodes nsp14", "nsp14 and", "and nsp16", "nsp16 which", "which possess", "possess guanine", "guanine n7", "n7 methyltransferase", "methyltransferase activity", "activity and", "and 2\u2019", "2\u2019 o", "o methyl", "methyl transferase", "transferase activity", "activity respectively", "2011 .", ". sars", "1 nsp14", "nsp14 generates", "generates 5'", "5' cap", "0 viral", "n7 methylated", "nsp16 further", "further methylates", "methylates cap", "viral rna.", "rna. these", "these viral", "rna modifications", "modifications mimic", "mimic the", "the 5'", "cap structure", "structure of", "of host", "host mrnas", "mrnas allowing", "allowing the", "the virus", "virus to", "to efficiently", "efficiently evade", "evade recognition", "recognition by", "by cytosolic", "cytosolic ddx58", "the nsp16", "nsp16 mediated", "mediated ribose", "ribose 2\u2032", "2\u2032 o", "o methylation", "methylation of", "rna also", "also blocks", "blocks the", "the antiviral", "of ifit1", "ifit1 complexes", "menachery vd", "vd et", "al. 2014", "2014 .", "the uridylate\u2010specific", "uridylate\u2010specific endoribonuclease", "activity of", "viral nsp15", "nsp15 degrades", "degrades viral", "rna to", "to hide", "hide it", "it from", "from innate", "bhardwaj k", "al. 2006", "ricagno s", "2006 .", ". moreover", "encodes several", "several proteins", "proteins that", "directly bind", "to host", "host targets", "targets associated", "associated with", "with sars\u2011cov\u20111", "sars\u2011cov\u20111 infection", "infection and", "and cytokine", "cytokine production", "frieman m", "m et", "hu y", "al. 2017", "kopecky bromberg", "bromberg sa", "sa et", "lindner h", "h et", "al. 2005", "siu kl", "kl et", "2009 .", "several such", "such binding", "binding events", "events and", "and their", "their consequences.", "consequences. for", "as a", "a de", "de ubiquitinating", "ubiquitinating enzyme", "viral nsp3", "nsp3 binds", "binds to", "to and", "and removes", "removes polyubiquitin", "polyubiquitin chains", "chains of", "of signaling", "signaling proteins", "proteins such", "as traf3", "and irf3", "irf3 thereby", "thereby modulating", "modulating the", "the formation", "formation of", "signaling complexes", "complexes and", "and the", "the activation", "activation of", "of irf3/7", "irf3/7 and", "and nfkappab", "sun l", "al. 2012", "chen x", "x et", "li sw", "sw et", "al. 2016", "2016 .", "this inhibits", "inhibits ifn", "production downstream", "downstream of", "of tlr7/8", "mavs and", "and sting", "sting signaling", "signaling pathways.", "pathways. binding", "binding of", "of sars", "1 nucleocapsid", "protein to", "to e3", "e3 ubiquitin", "ubiquitin ligase", "ligase trim25", "trim25 inhibits", "inhibits trim25", "trim25 mediated", "mediated ddx58", "ddx58 ubiquitination", "ubiquitination and", "and ddx58", "ddx58 mediated", "mediated signaling", "signaling pathway", "2017 .", ". next", "sars\u2011cov\u20111 membrane", "protein targets", "targets ibk1/ikbke", "ibk1/ikbke and", "and traf3", "traf3 to", "to prevent", "prevent the", "the traf3:tank:tbk1/ikbke", "traf3:tank:tbk1/ikbke complex", "complex and", "and thereby", "thereby inhibits", "inhibits tbk1/ikbke\u2011dependent", "tbk1/ikbke\u2011dependent activation", "of irf3/irf7", "irf3/irf7 transcription", "transcription factors", "factors downstream", "of ddx58", "ifih1 and", "and adaptor", "adaptor mavs", "the ion", "ion channel", "channel activities", "activities of", "of open", "open reading", "reading frame", "frame 3a", "orf3a or", "or 3a", "and e", "e contribute", "contribute to", "to activation", "the nlrp3", "nlrp3 inflammasome", "inflammasome leading", "leading to", "to highly", "highly inflammatory", "inflammatory pyroptotic", "pyroptotic cell", "cell death", "nieto\u2011torres jl", "jl et", "al. 2015", "chen iy", "iy et", "al. 2019", "yue y", "al. 2018", "2018 .", ". viral", "viral 3a", "3a promoted", "promoted the", "nlrp3 mediated", "mediated formation", "of pycard", "speck by", "by interaction", "interaction with", "with both", "both traf3", "traf3 and", "and pycard", "2019 .", ". binding", "of 3a", "3a to", "to caspase", "caspase 1", "enhanced casp1", "casp1 mediated", "mediated cleavage", "cleavage of", "of interleukin", "interleukin 1", "1 beta", "inflammasome pathway", ". like", "like 3a", "1 8b", "8b was", "was found", "found to", "to bind", "to nlrp3", "nlrp3 activating", "activating the", "inflammasome and", "and triggering", "triggering il\u20111\u03b2", "il\u20111\u03b2 release", "shi cs", "cs et", ". 8b", "was also", "also shown", "bind irf3", "inhibiting subsequent", "subsequent irf3", "irf3 dimerization", "wong et", ". at", "at the", "the plasma", "plasma membrane", "1 7a", "7a to", "host bst2", "bst2 disrupts", "disrupts the", "antiviral tethering", "tethering function", "of bst2", "bst2 which", "which restricts", "restricts the", "the release", "release of", "of diverse", "diverse mammalian", "mammalian enveloped", "enveloped viruses", "taylor jk", "jk et", "2015 .", "1 9b", "inhibits the", "the mavs", "mavs mediated", "mediated production", "production of", "of type", "i ifns", "ifns by", "by targeting", "targeting tomm70", "tomm70 on", "on the", "the mitochondria", "jiang hw", "hw et", "al. 2020", "2020 .", "1 6", "ifn signaling", "pathway by", "by tethering", "tethering karyopherins", "karyopherins kpna2", "kpna2 and", "and kpnb1", "kpnb1 to", "to the", "the endoplasmic", "endoplasmic reticulum", "er /golgi", "/golgi intermediate", "intermediate compartment", "and thus", "thus blocking", "blocking the", "the kpna1:kpnb1", "kpna1:kpnb1 dependent", "dependent nuclear", "nuclear import", "import of", "of stat1", "2007 .", "1 nsp1", "nsp1 to", "to peptidyl", "peptidyl prolyl", "prolyl isomerases", "and calcipressin", "calcipressin 3", "significantly activates", "activates the", "the cyclophilin", "cyclophilin a/nfat", "a/nfat pathway", "ultimately enhancing", "enhancing the", "the induction", "induction of", "the il", "il 2", "2 promoter", "pfefferle et", "et al", "law et", "at last", "sars\u2011cov\u20111 3b", "after translocating", "translocating to", "the nucleus", "to transcription", "transcription factor", "factor runx1", "runx1 and", "and increases", "increases its", "its promoting", "promoting activity", "varshney et", "2012 .", "coronaviruses covs", "covs are", "are positive sense", "positive sense rna", "sense rna viruses", "rna viruses that", "viruses that replicate", "that replicate in", "replicate in the", "in the interior", "the interior of", "interior of double", "of double membrane", "double membrane vesicles", "vesicles dmv", "dmv in", "in the cytoplasm", "the cytoplasm of", "cytoplasm of infected", "of infected cells", "cells stertz", "stertz s et", "s et al.", "et al. 2007", "2007 knoops", "knoops k et", "k et al.", "et al. 2008", "al. 2008 .", "2008 . the", ". the viral", "the viral replication", "viral replication and", "replication and transcription", "and transcription are", "transcription are facilitated", "are facilitated by", "facilitated by virus", "by virus encoded", "virus encoded non", "encoded non structural", "non structural proteins", "proteins sars", "cov 1 nsp1\u2013nsp16", "nsp1\u2013nsp16 that", "that assemble to", "assemble to form", "to form a", "form a dmv", "a dmv bound", "dmv bound replication", "bound replication transcription", "replication transcription complex", "complex rtc", "rtc . the", ". the replication", "the replication strategy", "replication strategy of", "strategy of covs", "of covs can", "covs can generate", "can generate both", "generate both single", "both single stranded", "single stranded rna", "rna ssrna", "ssrna and", "and double stranded", "double stranded rna", "rna dsrna", "dsrna species", "species that", "that may act", "may act as", "act as pathogen", "as pathogen associated", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "pamps recognized", "recognized by pattern", "by pattern recognition", "pattern recognition receptor", "receptor prr", "prr such", "such as toll", "as toll like", "toll like receptor", "like receptor 7", "7 tlr7", "tlr8 antiviral", "antiviral innate immune", "innate immune response", "immune response receptor", "response receptor rig", "receptor rig i", "i also", "also known as", "known as dead", "as dead box", "dead box protein", "box protein 58", "58 ddx58", "and interferon induced", "interferon induced helicase", "induced helicase c", "helicase c domain", "c domain containing", "domain containing protein", "containing protein 1", "1 ifih1", "ifih1 also", "known as mda5", "cervantes barragan l", "barragan l et", "l et al.", "2007 chen", "chen y et", "y et al.", "et al. 2009", "2009 2011", "2011 daffis", "daffis s et", "et al. 2010", "2010 li", "li y et", "et al. 2013", "al. 2013 .", "2013 . the", ". the activated", "the activated prrs", "activated prrs trigger", "prrs trigger signaling", "trigger signaling pathways", "signaling pathways to", "pathways to produce", "to produce type", "produce type i", "type i and", "i and type", "and type iii", "type iii interferons", "iii interferons ifns", "interferons ifns and", "ifns and proinflammatory", "and proinflammatory mediators", "proinflammatory mediators that", "mediators that perform", "that perform antiviral", "perform antiviral functions.", "antiviral functions. this", "functions. this reactome", "this reactome module", "reactome module describes", "module describes the", "describes the mechanisms", "the mechanisms underlying", "mechanisms underlying prr", "underlying prr mediated", "prr mediated sensing", "mediated sensing of", "sensing of the", "of the severe", "the severe acute", "severe acute respiratory", "acute respiratory syndrome", "respiratory syndrome coronavirus", "syndrome coronavirus type", "coronavirus type 1", "1 sars", "1 infection.", "first endosomal", "endosomal recognition of", "recognition of viral", "of viral ssrna", "viral ssrna occurs", "ssrna occurs by", "occurs by means", "by means of", "means of tlr7", "of tlr7 and", "tlr7 and tlr8", "and tlr8 which", "tlr8 which detect", "which detect gu", "detect gu rich", "gu rich ssrna", "rich ssrna sequences.", "ssrna sequences. specifically", "specifically gu", "rich ssrna oligonucleotides", "ssrna oligonucleotides derived", "oligonucleotides derived from", "derived from sars", "from sars cov", "cov 1 stimulated", "1 stimulated mononuclear", "stimulated mononuclear phagocytes", "mononuclear phagocytes to", "phagocytes to release", "to release considerable", "release considerable levels", "considerable levels of", "levels of pro\u2011inflammatory", "of pro\u2011inflammatory cytokines", "pro\u2011inflammatory cytokines tnf\u2011a", "tnf\u2011a il\u20116", "il\u20116 and il\u201112", "and il\u201112 via", "il\u201112 via tlr7", "via tlr7 and", "tlr8 li", "2013 . second", "second sars", "cov 1 dsrna", "1 dsrna replication", "dsrna replication intermediates", "replication intermediates can", "intermediates can be", "can be recognized", "be recognized by", "recognized by cytoplasmic", "by cytoplasmic receptors", "cytoplasmic receptors ddx58", "receptors ddx58 and", "ddx58 and ifih1", "and ifih1 which", "ifih1 which bind", "which bind to", "bind to mitochondrial", "to mitochondrial antiviral", "mitochondrial antiviral signaling", "antiviral signaling protein", "protein mavs", "mavs ips", "to induce the", "induce the ifn", "the ifn mediated", "ifn mediated antiviral", "mediated antiviral response.", "antiviral response. in", "response. in addition", "addition the", "the module shows", "module shows an", "shows an antiviral", "an antiviral function", "antiviral function of", "function of interferon", "of interferon induced", "interferon induced protein", "induced protein with", "protein with tetratricopeptide", "with tetratricopeptide repeats", "tetratricopeptide repeats 1", "1 ifit1", "ifit1 that", "that directly binds", "directly binds and", "binds and sequesters", "and sequesters viral", "sequesters viral single", "viral single stranded", "single stranded uncapped", "stranded uncapped 5\u2032", "uncapped 5\u2032 ppp", "5\u2032 ppp rna", "ppp rna and", "rna and cap", "and cap 0", "cap 0 rna", "rna daffis", "al. 2010 .", "2010 . this", ". this module", "this module also", "module also describes", "also describes several", "describes several strategies", "several strategies developed", "strategies developed by", "developed by sars", "by sars cov", "cov 1 to", "1 to evade", "to evade or", "evade or alter", "or alter host", "alter host immunity", "immunity including", "including escaping innate", "escaping innate immune", "innate immune sensors", "sensors inhibiting", "inhibiting ifn production", "ifn production and", "production and signaling", "signaling and", "and evading antiviral", "evading antiviral function", "function of ifn", "of ifn stimulated", "ifn stimulated gene", "gene isg", "isg products.", "products. for example", "example viral", "viral dsrna replication", "replication intermediates derived", "intermediates derived from", "derived from sars\u2011cov\u20111", "from sars\u2011cov\u20111 were", "sars\u2011cov\u20111 were shown", "were shown to", "shown to associate", "to associate with", "associate with rtc", "with rtc bound", "rtc bound to", "bound to double", "to double membrane", "vesicles which", "which protected viral", "protected viral rna", "viral rna from", "rna from sensing", "from sensing by", "sensing by ddx58", "by ddx58 or", "ddx58 or ifih1", "ifih1 stertz", "2008 . further", "further sars", "cov 1 encodes", "1 encodes nsp14", "encodes nsp14 and", "nsp14 and nsp16", "and nsp16 which", "nsp16 which possess", "which possess guanine", "possess guanine n7", "guanine n7 methyltransferase", "n7 methyltransferase activity", "methyltransferase activity and", "activity and 2\u2019", "and 2\u2019 o", "2\u2019 o methyl", "o methyl transferase", "methyl transferase activity", "transferase activity respectively", "respectively chen", "2011 . sars", ". sars cov", "cov 1 nsp14", "1 nsp14 generates", "nsp14 generates 5'", "generates 5' cap", "5' cap 0", "cap 0 viral", "0 viral rna", "rna m7gpppn", "m7gpppn guanine", "guanine n7 methylated", "methylated and", "and nsp16 further", "nsp16 further methylates", "further methylates cap", "methylates cap 0", "0 viral rna.", "viral rna. these", "rna. these viral", "these viral rna", "viral rna modifications", "rna modifications mimic", "modifications mimic the", "mimic the 5'", "the 5' cap", "5' cap structure", "cap structure of", "structure of host", "of host mrnas", "host mrnas allowing", "mrnas allowing the", "allowing the virus", "the virus to", "virus to efficiently", "to efficiently evade", "efficiently evade recognition", "evade recognition by", "recognition by cytosolic", "by cytosolic ddx58", "cytosolic ddx58 and", "ifih1 chen", "2010 . the", ". the nsp16", "the nsp16 mediated", "nsp16 mediated ribose", "mediated ribose 2\u2032", "ribose 2\u2032 o", "2\u2032 o methylation", "o methylation of", "methylation of viral", "of viral rna", "viral rna also", "rna also blocks", "also blocks the", "blocks the antiviral", "the antiviral function", "function of ifit1", "of ifit1 complexes", "complexes menachery", "menachery vd et", "vd et al.", "et al. 2014", "al. 2014 .", "2014 . further", "further the", "the uridylate\u2010specific endoribonuclease", "endoribonuclease endou", "endou activity", "activity of viral", "of viral nsp15", "viral nsp15 degrades", "nsp15 degrades viral", "degrades viral rna", "viral rna to", "rna to hide", "to hide it", "hide it from", "it from innate", "from innate immune", "sensors bhardwaj", "bhardwaj k et", "et al. 2006", "2006 ricagno", "ricagno s et", "al. 2006 .", "2006 . moreover", "moreover sars", "1 encodes several", "encodes several proteins", "several proteins that", "proteins that directly", "that directly bind", "directly bind to", "bind to host", "to host targets", "host targets associated", "targets associated with", "associated with sars\u2011cov\u20111", "with sars\u2011cov\u20111 infection", "sars\u2011cov\u20111 infection and", "infection and cytokine", "and cytokine production", "production frieman", "frieman m et", "m et al.", "2009 hu", "hu y et", "et al. 2017", "2017 kopecky", "kopecky bromberg sa", "bromberg sa et", "sa et al.", "2007 lindner", "lindner h et", "h et al.", "et al. 2005", "2005 siu", "siu kl et", "kl et al.", "al. 2009 .", "2009 . this", ". this reactome", "module describes several", "describes several such", "several such binding", "such binding events", "binding events and", "events and their", "and their consequences.", "their consequences. for", "consequences. for example", "example as", "as a de", "a de ubiquitinating", "de ubiquitinating enzyme", "enzyme viral", "viral nsp3 binds", "nsp3 binds to", "binds to and", "to and removes", "and removes polyubiquitin", "removes polyubiquitin chains", "polyubiquitin chains of", "chains of signaling", "of signaling proteins", "signaling proteins such", "proteins such as", "such as traf3", "traf3 traf6", "traf6 sting", "sting ikba", "ikba and", "and irf3 thereby", "irf3 thereby modulating", "thereby modulating the", "modulating the formation", "the formation of", "formation of signaling", "of signaling complexes", "signaling complexes and", "complexes and the", "and the activation", "the activation of", "activation of irf3/7", "of irf3/7 and", "irf3/7 and nfkappab", "nfkappab sun", "sun l et", "et al. 2012", "2012 chen", "chen x et", "x et al.", "2014 li", "li sw et", "sw et al.", "et al. 2016", "al. 2016 .", "2016 . this", ". this inhibits", "this inhibits ifn", "inhibits ifn production", "ifn production downstream", "production downstream of", "downstream of tlr7/8", "tlr7/8 ddx58", "ddx58 ifih1", "ifih1 mavs", "mavs and sting", "and sting signaling", "sting signaling pathways.", "signaling pathways. binding", "pathways. binding of", "binding of sars", "of sars cov", "cov 1 nucleocapsid", "nucleocapsid n", "n protein", "protein to e3", "to e3 ubiquitin", "e3 ubiquitin ligase", "ubiquitin ligase trim25", "ligase trim25 inhibits", "trim25 inhibits trim25", "inhibits trim25 mediated", "trim25 mediated ddx58", "mediated ddx58 ubiquitination", "ddx58 ubiquitination and", "ubiquitination and ddx58", "and ddx58 mediated", "ddx58 mediated signaling", "mediated signaling pathway", "pathway hu", "al. 2017 .", "2017 . next", "next sars\u2011cov\u20111", "membrane m", "m protein", "protein targets ibk1/ikbke", "targets ibk1/ikbke and", "ibk1/ikbke and traf3", "and traf3 to", "traf3 to prevent", "to prevent the", "prevent the formation", "formation of the", "of the traf3:tank:tbk1/ikbke", "the traf3:tank:tbk1/ikbke complex", "traf3:tank:tbk1/ikbke complex and", "complex and thereby", "and thereby inhibits", "thereby inhibits tbk1/ikbke\u2011dependent", "inhibits tbk1/ikbke\u2011dependent activation", "tbk1/ikbke\u2011dependent activation of", "activation of irf3/irf7", "of irf3/irf7 transcription", "irf3/irf7 transcription factors", "transcription factors downstream", "factors downstream of", "downstream of ddx58", "ifih1 and adaptor", "and adaptor mavs", "mavs siu", "2009 2014", "2014 . the", ". the ion", "the ion channel", "ion channel activities", "channel activities of", "activities of open", "of open reading", "open reading frame", "reading frame 3a", "3a orf3a", "orf3a or 3a", "3a and", "and e contribute", "e contribute to", "contribute to activation", "to activation of", "activation of the", "of the nlrp3", "the nlrp3 inflammasome", "nlrp3 inflammasome leading", "inflammasome leading to", "leading to highly", "to highly inflammatory", "highly inflammatory pyroptotic", "inflammatory pyroptotic cell", "pyroptotic cell death", "death nieto\u2011torres", "nieto\u2011torres jl et", "jl et al.", "et al. 2015", "2015 chen", "chen iy et", "iy et al.", "et al. 2019", "2019 yue", "yue y et", "et al. 2018", "al. 2018 .", "2018 . viral", ". viral 3a", "viral 3a promoted", "3a promoted the", "promoted the nlrp3", "the nlrp3 mediated", "nlrp3 mediated formation", "mediated formation of", "formation of pycard", "pycard asc", "asc speck", "speck by interaction", "by interaction with", "interaction with both", "with both traf3", "both traf3 and", "traf3 and pycard", "al. 2019 .", "2019 . binding", ". binding of", "binding of 3a", "of 3a to", "3a to caspase", "to caspase 1", "1 casp1", "casp1 enhanced", "enhanced casp1 mediated", "casp1 mediated cleavage", "mediated cleavage of", "cleavage of interleukin", "of interleukin 1", "interleukin 1 beta", "beta il\u20111\u03b2", "il\u20111\u03b2 downstream", "downstream of the", "nlrp3 inflammasome pathway", "pathway yue", "2018 . like", ". like 3a", "3a sars", "cov 1 8b", "1 8b was", "8b was found", "was found to", "found to bind", "to bind to", "bind to nlrp3", "to nlrp3 activating", "nlrp3 activating the", "activating the nlrp3", "nlrp3 inflammasome and", "inflammasome and triggering", "and triggering il\u20111\u03b2", "triggering il\u20111\u03b2 release", "release shi", "shi cs et", "cs et al.", "2019 . 8b", ". 8b was", "8b was also", "was also shown", "also shown to", "shown to bind", "to bind irf3", "irf3 inhibiting", "inhibiting subsequent irf3", "subsequent irf3 dimerization", "dimerization wong", "wong et al.", "2018 . at", ". at the", "at the plasma", "the plasma membrane", "membrane binding", "cov 1 7a", "1 7a to", "7a to host", "to host bst2", "host bst2 disrupts", "bst2 disrupts the", "disrupts the antiviral", "the antiviral tethering", "antiviral tethering function", "tethering function of", "function of bst2", "of bst2 which", "bst2 which restricts", "which restricts the", "restricts the release", "the release of", "release of diverse", "of diverse mammalian", "diverse mammalian enveloped", "mammalian enveloped viruses", "viruses taylor", "taylor jk et", "jk et al.", "al. 2015 .", "2015 . sars", "cov 1 9b", "9b orf9b", "orf9b inhibits", "inhibits the mavs", "the mavs mediated", "mavs mediated production", "mediated production of", "production of type", "of type i", "type i ifns", "i ifns by", "ifns by targeting", "by targeting tomm70", "targeting tomm70 on", "tomm70 on the", "on the mitochondria", "mitochondria jiang", "jiang hw et", "hw et al.", "et al. 2020", "al. 2020 .", "2020 . sars", "cov 1 6", "6 orf6", "orf6 inhibits", "inhibits the ifn", "the ifn signaling", "ifn signaling pathway", "signaling pathway by", "pathway by tethering", "by tethering karyopherins", "tethering karyopherins kpna2", "karyopherins kpna2 and", "kpna2 and kpnb1", "and kpnb1 to", "kpnb1 to the", "to the endoplasmic", "the endoplasmic reticulum", "reticulum er", "er /golgi intermediate", "/golgi intermediate compartment", "compartment ergic", "ergic and", "and thus blocking", "thus blocking the", "blocking the kpna1:kpnb1", "the kpna1:kpnb1 dependent", "kpna1:kpnb1 dependent nuclear", "dependent nuclear import", "nuclear import of", "import of stat1", "stat1 frieman", "al. 2007 .", "2007 . binding", "cov 1 nsp1", "1 nsp1 to", "nsp1 to peptidyl", "to peptidyl prolyl", "peptidyl prolyl isomerases", "isomerases ppiases", "ppiases and", "and calcipressin 3", "3 rcan3", "rcan3 significantly", "significantly activates the", "activates the cyclophilin", "the cyclophilin a/nfat", "cyclophilin a/nfat pathway", "pathway ultimately", "ultimately enhancing the", "enhancing the induction", "the induction of", "induction of the", "of the il", "the il 2", "il 2 promoter", "promoter pfefferle", "pfefferle et al", "al 2011", "2011 law", "law et al", "al 2007", "2007 . at", ". at last", "last sars\u2011cov\u20111", "3b after", "after translocating to", "translocating to the", "to the nucleus", "nucleus binds", "binds to transcription", "to transcription factor", "transcription factor runx1", "factor runx1 and", "runx1 and increases", "and increases its", "increases its promoting", "its promoting activity", "activity varshney", "varshney et al", "al 2012", "covs are positive", "are positive sense rna", "positive sense rna viruses", "sense rna viruses that", "rna viruses that replicate", "viruses that replicate in", "that replicate in the", "replicate in the interior", "in the interior of", "the interior of double", "interior of double membrane", "of double membrane vesicles", "membrane vesicles dmv", "dmv in the", "in the cytoplasm of", "the cytoplasm of infected", "cytoplasm of infected cells", "infected cells stertz", "cells stertz s", "stertz s et al.", "s et al. 2007", "al. 2007 knoops", "2007 knoops k", "knoops k et al.", "k et al. 2008", "et al. 2008 .", "al. 2008 . the", "2008 . the viral", ". the viral replication", "the viral replication and", "viral replication and transcription", "replication and transcription are", "and transcription are facilitated", "transcription are facilitated by", "are facilitated by virus", "facilitated by virus encoded", "by virus encoded non", "virus encoded non structural", "encoded non structural proteins", "structural proteins sars", "proteins sars cov", "sars cov 1 nsp1\u2013nsp16", "1 nsp1\u2013nsp16 that", "nsp1\u2013nsp16 that assemble", "that assemble to form", "assemble to form a", "to form a dmv", "form a dmv bound", "a dmv bound replication", "dmv bound replication transcription", "bound replication transcription complex", "transcription complex rtc", "complex rtc .", "rtc . the replication", ". the replication strategy", "the replication strategy of", "replication strategy of covs", "strategy of covs can", "of covs can generate", "covs can generate both", "can generate both single", "generate both single stranded", "both single stranded rna", "stranded rna ssrna", "ssrna and double", "and double stranded rna", "stranded rna dsrna", "species that may", "that may act as", "may act as pathogen", "act as pathogen associated", "as pathogen associated molecular", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps recognized by", "recognized by pattern recognition", "by pattern recognition receptor", "recognition receptor prr", "prr such as", "such as toll like", "as toll like receptor", "toll like receptor 7", "receptor 7 tlr7", "and tlr8 antiviral", "tlr8 antiviral innate", "antiviral innate immune response", "innate immune response receptor", "immune response receptor rig", "response receptor rig i", "rig i also", "i also known", "also known as dead", "known as dead box", "as dead box protein", "dead box protein 58", "protein 58 ddx58", "ddx58 and interferon", "and interferon induced helicase", "interferon induced helicase c", "induced helicase c domain", "helicase c domain containing", "c domain containing protein", "domain containing protein 1", "protein 1 ifih1", "ifih1 also known", "also known as mda5", "mda5 cervantes", "cervantes barragan l et", "barragan l et al.", "l et al. 2007", "al. 2007 chen", "2007 chen y", "chen y et al.", "y et al. 2009", "al. 2009 2011", "2011 daffis s", "daffis s et al.", "s et al. 2010", "al. 2010 li", "2010 li y", "li y et al.", "y et al. 2013", "et al. 2013 .", "al. 2013 . the", "2013 . the activated", ". the activated prrs", "the activated prrs trigger", "activated prrs trigger signaling", "prrs trigger signaling pathways", "trigger signaling pathways to", "signaling pathways to produce", "pathways to produce type", "to produce type i", "produce type i and", "type i and type", "i and type iii", "and type iii interferons", "type iii interferons ifns", "iii interferons ifns and", "interferons ifns and proinflammatory", "ifns and proinflammatory mediators", "and proinflammatory mediators that", "proinflammatory mediators that perform", "mediators that perform antiviral", "that perform antiviral functions.", "perform antiviral functions. this", "antiviral functions. this reactome", "functions. this reactome module", "this reactome module describes", "reactome module describes the", "module describes the mechanisms", "describes the mechanisms underlying", "the mechanisms underlying prr", "mechanisms underlying prr mediated", "underlying prr mediated sensing", "prr mediated sensing of", "mediated sensing of the", "sensing of the severe", "of the severe acute", "the severe acute respiratory", "severe acute respiratory syndrome", "acute respiratory syndrome coronavirus", "respiratory syndrome coronavirus type", "syndrome coronavirus type 1", "type 1 sars", "1 sars cov", "cov 1 infection.", "1 infection. first", "infection. first endosomal", "first endosomal recognition", "endosomal recognition of viral", "recognition of viral ssrna", "of viral ssrna occurs", "viral ssrna occurs by", "ssrna occurs by means", "occurs by means of", "by means of tlr7", "means of tlr7 and", "of tlr7 and tlr8", "tlr7 and tlr8 which", "and tlr8 which detect", "tlr8 which detect gu", "which detect gu rich", "detect gu rich ssrna", "gu rich ssrna sequences.", "rich ssrna sequences. specifically", "sequences. specifically gu", "specifically gu rich", "gu rich ssrna oligonucleotides", "rich ssrna oligonucleotides derived", "ssrna oligonucleotides derived from", "oligonucleotides derived from sars", "derived from sars cov", "from sars cov 1", "sars cov 1 stimulated", "cov 1 stimulated mononuclear", "1 stimulated mononuclear phagocytes", "stimulated mononuclear phagocytes to", "mononuclear phagocytes to release", "phagocytes to release considerable", "to release considerable levels", "release considerable levels of", "considerable levels of pro\u2011inflammatory", "levels of pro\u2011inflammatory cytokines", "of pro\u2011inflammatory cytokines tnf\u2011a", "cytokines tnf\u2011a il\u20116", "tnf\u2011a il\u20116 and", "il\u20116 and il\u201112 via", "and il\u201112 via tlr7", "il\u201112 via tlr7 and", "via tlr7 and tlr8", "and tlr8 li", "tlr8 li y", "al. 2013 . second", ". second sars", "second sars cov", "sars cov 1 dsrna", "cov 1 dsrna replication", "1 dsrna replication intermediates", "dsrna replication intermediates can", "replication intermediates can be", "intermediates can be recognized", "can be recognized by", "be recognized by cytoplasmic", "recognized by cytoplasmic receptors", "by cytoplasmic receptors ddx58", "cytoplasmic receptors ddx58 and", "receptors ddx58 and ifih1", "ddx58 and ifih1 which", "and ifih1 which bind", "ifih1 which bind to", "which bind to mitochondrial", "bind to mitochondrial antiviral", "to mitochondrial antiviral signaling", "mitochondrial antiviral signaling protein", "signaling protein mavs", "mavs ips 1", "ips 1 to", "1 to induce", "to induce the ifn", "induce the ifn mediated", "the ifn mediated antiviral", "ifn mediated antiviral response.", "mediated antiviral response. in", "antiviral response. in addition", "in addition the", "addition the module", "the module shows an", "module shows an antiviral", "shows an antiviral function", "an antiviral function of", "antiviral function of interferon", "function of interferon induced", "of interferon induced protein", "interferon induced protein with", "induced protein with tetratricopeptide", "protein with tetratricopeptide repeats", "with tetratricopeptide repeats 1", "repeats 1 ifit1", "ifit1 that directly", "that directly binds and", "directly binds and sequesters", "binds and sequesters viral", "and sequesters viral single", "sequesters viral single stranded", "viral single stranded uncapped", "single stranded uncapped 5\u2032", "stranded uncapped 5\u2032 ppp", "uncapped 5\u2032 ppp rna", "5\u2032 ppp rna and", "ppp rna and cap", "rna and cap 0", "and cap 0 rna", "0 rna daffis", "rna daffis s", "et al. 2010 .", "al. 2010 . this", "2010 . this module", ". this module also", "this module also describes", "module also describes several", "also describes several strategies", "describes several strategies developed", "several strategies developed by", "strategies developed by sars", "developed by sars cov", "by sars cov 1", "sars cov 1 to", "cov 1 to evade", "1 to evade or", "to evade or alter", "evade or alter host", "or alter host immunity", "host immunity including", "immunity including escaping", "including escaping innate immune", "escaping innate immune sensors", "immune sensors inhibiting", "sensors inhibiting ifn", "inhibiting ifn production and", "ifn production and signaling", "and signaling and", "signaling and evading", "and evading antiviral function", "evading antiviral function of", "antiviral function of ifn", "function of ifn stimulated", "of ifn stimulated gene", "stimulated gene isg", "isg products. for", "for example viral", "example viral dsrna", "viral dsrna replication intermediates", "dsrna replication intermediates derived", "replication intermediates derived from", "intermediates derived from sars\u2011cov\u20111", "derived from sars\u2011cov\u20111 were", "from sars\u2011cov\u20111 were shown", "sars\u2011cov\u20111 were shown to", "were shown to associate", "shown to associate with", "to associate with rtc", "associate with rtc bound", "with rtc bound to", "rtc bound to double", "bound to double membrane", "to double membrane vesicles", "membrane vesicles which", "vesicles which protected", "which protected viral rna", "protected viral rna from", "viral rna from sensing", "rna from sensing by", "from sensing by ddx58", "sensing by ddx58 or", "by ddx58 or ifih1", "or ifih1 stertz", "ifih1 stertz s", "al. 2008 . further", ". further sars", "further sars cov", "sars cov 1 encodes", "cov 1 encodes nsp14", "1 encodes nsp14 and", "encodes nsp14 and nsp16", "nsp14 and nsp16 which", "and nsp16 which possess", "nsp16 which possess guanine", "which possess guanine n7", "possess guanine n7 methyltransferase", "guanine n7 methyltransferase activity", "n7 methyltransferase activity and", "methyltransferase activity and 2\u2019", "activity and 2\u2019 o", "and 2\u2019 o methyl", "2\u2019 o methyl transferase", "o methyl transferase activity", "methyl transferase activity respectively", "activity respectively chen", "respectively chen y", "2009 2011 .", "2011 . sars cov", ". sars cov 1", "sars cov 1 nsp14", "cov 1 nsp14 generates", "1 nsp14 generates 5'", "nsp14 generates 5' cap", "generates 5' cap 0", "5' cap 0 viral", "cap 0 viral rna", "viral rna m7gpppn", "m7gpppn guanine n7", "n7 methylated and", "methylated and nsp16", "and nsp16 further methylates", "nsp16 further methylates cap", "further methylates cap 0", "methylates cap 0 viral", "cap 0 viral rna.", "0 viral rna. these", "viral rna. these viral", "rna. these viral rna", "these viral rna modifications", "viral rna modifications mimic", "rna modifications mimic the", "modifications mimic the 5'", "mimic the 5' cap", "the 5' cap structure", "5' cap structure of", "cap structure of host", "structure of host mrnas", "of host mrnas allowing", "host mrnas allowing the", "mrnas allowing the virus", "allowing the virus to", "the virus to efficiently", "virus to efficiently evade", "to efficiently evade recognition", "efficiently evade recognition by", "evade recognition by cytosolic", "recognition by cytosolic ddx58", "by cytosolic ddx58 and", "cytosolic ddx58 and ifih1", "and ifih1 chen", "ifih1 chen y", "al. 2010 . the", "2010 . the nsp16", ". the nsp16 mediated", "the nsp16 mediated ribose", "nsp16 mediated ribose 2\u2032", "mediated ribose 2\u2032 o", "ribose 2\u2032 o methylation", "2\u2032 o methylation of", "o methylation of viral", "methylation of viral rna", "of viral rna also", "viral rna also blocks", "rna also blocks the", "also blocks the antiviral", "blocks the antiviral function", "the antiviral function of", "antiviral function of ifit1", "function of ifit1 complexes", "ifit1 complexes menachery", "complexes menachery vd", "menachery vd et al.", "vd et al. 2014", "et al. 2014 .", "al. 2014 . further", ". further the", "further the uridylate\u2010specific", "uridylate\u2010specific endoribonuclease endou", "endou activity of", "activity of viral nsp15", "of viral nsp15 degrades", "viral nsp15 degrades viral", "nsp15 degrades viral rna", "degrades viral rna to", "viral rna to hide", "rna to hide it", "to hide it from", "hide it from innate", "it from innate immune", "from innate immune sensors", "immune sensors bhardwaj", "sensors bhardwaj k", "bhardwaj k et al.", "k et al. 2006", "al. 2006 ricagno", "2006 ricagno s", "ricagno s et al.", "s et al. 2006", "et al. 2006 .", "al. 2006 . moreover", ". moreover sars", "moreover sars cov", "cov 1 encodes several", "1 encodes several proteins", "encodes several proteins that", "several proteins that directly", "proteins that directly bind", "that directly bind to", "directly bind to host", "bind to host targets", "to host targets associated", "host targets associated with", "targets associated with sars\u2011cov\u20111", "associated with sars\u2011cov\u20111 infection", "with sars\u2011cov\u20111 infection and", "sars\u2011cov\u20111 infection and cytokine", "infection and cytokine production", "cytokine production frieman", "production frieman m", "frieman m et al.", "m et al. 2009", "al. 2009 hu", "2009 hu y", "hu y et al.", "y et al. 2017", "al. 2017 kopecky", "2017 kopecky bromberg", "kopecky bromberg sa et", "bromberg sa et al.", "sa et al. 2007", "al. 2007 lindner", "2007 lindner h", "lindner h et al.", "h et al. 2005", "al. 2005 siu", "2005 siu kl", "siu kl et al.", "kl et al. 2009", "et al. 2009 .", "al. 2009 . this", "2009 . this reactome", ". this reactome module", "reactome module describes several", "module describes several such", "describes several such binding", "several such binding events", "such binding events and", "binding events and their", "events and their consequences.", "and their consequences. for", "their consequences. for example", "for example as", "example as a", "as a de ubiquitinating", "a de ubiquitinating enzyme", "ubiquitinating enzyme viral", "enzyme viral nsp3", "viral nsp3 binds to", "nsp3 binds to and", "binds to and removes", "to and removes polyubiquitin", "and removes polyubiquitin chains", "removes polyubiquitin chains of", "polyubiquitin chains of signaling", "chains of signaling proteins", "of signaling proteins such", "signaling proteins such as", "proteins such as traf3", "as traf3 traf6", "ikba and irf3", "and irf3 thereby modulating", "irf3 thereby modulating the", "thereby modulating the formation", "modulating the formation of", "the formation of signaling", "formation of signaling complexes", "of signaling complexes and", "signaling complexes and the", "complexes and the activation", "and the activation of", "the activation of irf3/7", "activation of irf3/7 and", "of irf3/7 and nfkappab", "and nfkappab sun", "nfkappab sun l", "sun l et al.", "l et al. 2012", "al. 2012 chen", "2012 chen x", "chen x et al.", "x et al. 2014", "al. 2014 li", "2014 li sw", "li sw et al.", "sw et al. 2016", "et al. 2016 .", "al. 2016 . this", "2016 . this inhibits", ". this inhibits ifn", "this inhibits ifn production", "inhibits ifn production downstream", "ifn production downstream of", "production downstream of tlr7/8", "of tlr7/8 ddx58", "ifih1 mavs and", "mavs and sting signaling", "and sting signaling pathways.", "sting signaling pathways. binding", "signaling pathways. binding of", "pathways. binding of sars", "binding of sars cov", "of sars cov 1", "sars cov 1 nucleocapsid", "1 nucleocapsid n", "n protein to", "protein to e3 ubiquitin", "to e3 ubiquitin ligase", "e3 ubiquitin ligase trim25", "ubiquitin ligase trim25 inhibits", "ligase trim25 inhibits trim25", "trim25 inhibits trim25 mediated", "inhibits trim25 mediated ddx58", "trim25 mediated ddx58 ubiquitination", "mediated ddx58 ubiquitination and", "ddx58 ubiquitination and ddx58", "ubiquitination and ddx58 mediated", "and ddx58 mediated signaling", "ddx58 mediated signaling pathway", "signaling pathway hu", "pathway hu y", "et al. 2017 .", "al. 2017 . next", ". next sars\u2011cov\u20111", "next sars\u2011cov\u20111 membrane", "sars\u2011cov\u20111 membrane m", "m protein targets", "protein targets ibk1/ikbke and", "targets ibk1/ikbke and traf3", "ibk1/ikbke and traf3 to", "and traf3 to prevent", "traf3 to prevent the", "to prevent the formation", "prevent the formation of", "the formation of the", "formation of the traf3:tank:tbk1/ikbke", "of the traf3:tank:tbk1/ikbke complex", "the traf3:tank:tbk1/ikbke complex and", "traf3:tank:tbk1/ikbke complex and thereby", "complex and thereby inhibits", "and thereby inhibits tbk1/ikbke\u2011dependent", "thereby inhibits tbk1/ikbke\u2011dependent activation", "inhibits tbk1/ikbke\u2011dependent activation of", "tbk1/ikbke\u2011dependent activation of irf3/irf7", "activation of irf3/irf7 transcription", "of irf3/irf7 transcription factors", "irf3/irf7 transcription factors downstream", "transcription factors downstream of", "factors downstream of ddx58", "of ddx58 ifih1", "ddx58 ifih1 and", "ifih1 and adaptor mavs", "adaptor mavs siu", "mavs siu kl", "al. 2009 2014", "2009 2014 .", "2014 . the ion", ". the ion channel", "the ion channel activities", "ion channel activities of", "channel activities of open", "activities of open reading", "of open reading frame", "open reading frame 3a", "frame 3a orf3a", "3a orf3a or", "or 3a and", "3a and e", "and e contribute to", "e contribute to activation", "contribute to activation of", "to activation of the", "activation of the nlrp3", "of the nlrp3 inflammasome", "the nlrp3 inflammasome leading", "nlrp3 inflammasome leading to", "inflammasome leading to highly", "leading to highly inflammatory", "to highly inflammatory pyroptotic", "highly inflammatory pyroptotic cell", "inflammatory pyroptotic cell death", "cell death nieto\u2011torres", "death nieto\u2011torres jl", "nieto\u2011torres jl et al.", "jl et al. 2015", "al. 2015 chen", "2015 chen iy", "chen iy et al.", "iy et al. 2019", "al. 2019 yue", "2019 yue y", "yue y et al.", "y et al. 2018", "et al. 2018 .", "al. 2018 . viral", "2018 . viral 3a", ". viral 3a promoted", "viral 3a promoted the", "3a promoted the nlrp3", "promoted the nlrp3 mediated", "the nlrp3 mediated formation", "nlrp3 mediated formation of", "mediated formation of pycard", "of pycard asc", "asc speck by", "speck by interaction with", "by interaction with both", "interaction with both traf3", "with both traf3 and", "both traf3 and pycard", "and pycard asc", "asc siu", "kl et al. 2019", "et al. 2019 .", "al. 2019 . binding", "2019 . binding of", ". binding of 3a", "binding of 3a to", "of 3a to caspase", "3a to caspase 1", "caspase 1 casp1", "casp1 enhanced casp1", "enhanced casp1 mediated cleavage", "casp1 mediated cleavage of", "mediated cleavage of interleukin", "cleavage of interleukin 1", "of interleukin 1 beta", "1 beta il\u20111\u03b2", "il\u20111\u03b2 downstream of", "downstream of the nlrp3", "the nlrp3 inflammasome pathway", "inflammasome pathway yue", "pathway yue y", "al. 2018 . like", "2018 . like 3a", "like 3a sars", "3a sars cov", "sars cov 1 8b", "cov 1 8b was", "1 8b was found", "8b was found to", "was found to bind", "found to bind to", "to bind to nlrp3", "bind to nlrp3 activating", "to nlrp3 activating the", "nlrp3 activating the nlrp3", "activating the nlrp3 inflammasome", "the nlrp3 inflammasome and", "nlrp3 inflammasome and triggering", "inflammasome and triggering il\u20111\u03b2", "and triggering il\u20111\u03b2 release", "il\u20111\u03b2 release shi", "release shi cs", "shi cs et al.", "cs et al. 2019", "al. 2019 . 8b", "2019 . 8b was", ". 8b was also", "8b was also shown", "was also shown to", "also shown to bind", "shown to bind irf3", "bind irf3 inhibiting", "irf3 inhibiting subsequent", "inhibiting subsequent irf3 dimerization", "irf3 dimerization wong", "dimerization wong et", "wong et al. 2018", "al. 2018 . at", "2018 . at the", ". at the plasma", "at the plasma membrane", "plasma membrane binding", "membrane binding of", "sars cov 1 7a", "cov 1 7a to", "1 7a to host", "7a to host bst2", "to host bst2 disrupts", "host bst2 disrupts the", "bst2 disrupts the antiviral", "disrupts the antiviral tethering", "the antiviral tethering function", "antiviral tethering function of", "tethering function of bst2", "function of bst2 which", "of bst2 which restricts", "bst2 which restricts the", "which restricts the release", "restricts the release of", "the release of diverse", "release of diverse mammalian", "of diverse mammalian enveloped", "diverse mammalian enveloped viruses", "enveloped viruses taylor", "viruses taylor jk", "taylor jk et al.", "jk et al. 2015", "et al. 2015 .", "al. 2015 . sars", "2015 . sars cov", "sars cov 1 9b", "1 9b orf9b", "orf9b inhibits the", "inhibits the mavs mediated", "the mavs mediated production", "mavs mediated production of", "mediated production of type", "production of type i", "of type i ifns", "type i ifns by", "i ifns by targeting", "ifns by targeting tomm70", "by targeting tomm70 on", "targeting tomm70 on the", "tomm70 on the mitochondria", "the mitochondria jiang", "mitochondria jiang hw", "jiang hw et al.", "hw et al. 2020", "et al. 2020 .", "al. 2020 . sars", "2020 . sars cov", "sars cov 1 6", "1 6 orf6", "orf6 inhibits the", "inhibits the ifn signaling", "the ifn signaling pathway", "ifn signaling pathway by", "signaling pathway by tethering", "pathway by tethering karyopherins", "by tethering karyopherins kpna2", "tethering karyopherins kpna2 and", "karyopherins kpna2 and kpnb1", "kpna2 and kpnb1 to", "and kpnb1 to the", "kpnb1 to the endoplasmic", "to the endoplasmic reticulum", "endoplasmic reticulum er", "reticulum er /golgi", "er /golgi intermediate compartment", "intermediate compartment ergic", "ergic and thus", "and thus blocking the", "thus blocking the kpna1:kpnb1", "blocking the kpna1:kpnb1 dependent", "the kpna1:kpnb1 dependent nuclear", "kpna1:kpnb1 dependent nuclear import", "dependent nuclear import of", "nuclear import of stat1", "of stat1 frieman", "stat1 frieman m", "m et al. 2007", "et al. 2007 .", "al. 2007 . binding", "2007 . binding of", ". binding of sars", "sars cov 1 nsp1", "cov 1 nsp1 to", "1 nsp1 to peptidyl", "nsp1 to peptidyl prolyl", "to peptidyl prolyl isomerases", "prolyl isomerases ppiases", "ppiases and calcipressin", "calcipressin 3 rcan3", "rcan3 significantly activates", "significantly activates the cyclophilin", "activates the cyclophilin a/nfat", "the cyclophilin a/nfat pathway", "a/nfat pathway ultimately", "pathway ultimately enhancing", "ultimately enhancing the induction", "enhancing the induction of", "the induction of the", "induction of the il", "of the il 2", "the il 2 promoter", "2 promoter pfefferle", "promoter pfefferle et", "et al 2011", "2011 law et", "et al 2007", "al 2007 .", "2007 . at last", "at last sars\u2011cov\u20111", "last sars\u2011cov\u20111 3b", "sars\u2011cov\u20111 3b after", "3b after translocating", "after translocating to the", "translocating to the nucleus", "the nucleus binds", "nucleus binds to", "binds to transcription factor", "to transcription factor runx1", "transcription factor runx1 and", "factor runx1 and increases", "runx1 and increases its", "and increases its promoting", "increases its promoting activity", "promoting activity varshney", "activity varshney et", "et al 2012", "al 2012 .", "coronaviruses covs are", "covs are positive sense", "are positive sense rna viruses", "positive sense rna viruses that", "sense rna viruses that replicate", "rna viruses that replicate in", "viruses that replicate in the", "that replicate in the interior", "replicate in the interior of", "in the interior of double", "the interior of double membrane", "interior of double membrane vesicles", "double membrane vesicles dmv", "vesicles dmv in", "dmv in the cytoplasm", "in the cytoplasm of infected", "the cytoplasm of infected cells", "of infected cells stertz", "infected cells stertz s", "cells stertz s et", "stertz s et al. 2007", "et al. 2007 knoops", "al. 2007 knoops k", "2007 knoops k et", "knoops k et al. 2008", "k et al. 2008 .", "et al. 2008 . the", "al. 2008 . the viral", "2008 . the viral replication", ". the viral replication and", "the viral replication and transcription", "viral replication and transcription are", "replication and transcription are facilitated", "and transcription are facilitated by", "transcription are facilitated by virus", "are facilitated by virus encoded", "facilitated by virus encoded non", "by virus encoded non structural", "virus encoded non structural proteins", "non structural proteins sars", "structural proteins sars cov", "proteins sars cov 1", "cov 1 nsp1\u2013nsp16 that", "1 nsp1\u2013nsp16 that assemble", "nsp1\u2013nsp16 that assemble to", "that assemble to form a", "assemble to form a dmv", "to form a dmv bound", "form a dmv bound replication", "a dmv bound replication transcription", "dmv bound replication transcription complex", "replication transcription complex rtc", "transcription complex rtc .", "complex rtc . the", "rtc . the replication strategy", ". the replication strategy of", "the replication strategy of covs", "replication strategy of covs can", "strategy of covs can generate", "of covs can generate both", "covs can generate both single", "can generate both single stranded", "generate both single stranded rna", "single stranded rna ssrna", "rna ssrna and", "ssrna and double stranded", "double stranded rna dsrna", "rna dsrna species", "dsrna species that", "species that may act", "that may act as pathogen", "may act as pathogen associated", "act as pathogen associated molecular", "as pathogen associated molecular patterns", "associated molecular patterns pamps", "patterns pamps recognized", "pamps recognized by pattern", "recognized by pattern recognition receptor", "pattern recognition receptor prr", "receptor prr such", "prr such as toll", "such as toll like receptor", "as toll like receptor 7", "like receptor 7 tlr7", "7 tlr7 and", "and tlr8 antiviral innate", "tlr8 antiviral innate immune", "antiviral innate immune response receptor", "innate immune response receptor rig", "immune response receptor rig i", "receptor rig i also", "rig i also known", "i also known as", "also known as dead box", "known as dead box protein", "as dead box protein 58", "box protein 58 ddx58", "58 ddx58 and", "ddx58 and interferon induced", "and interferon induced helicase c", "interferon induced helicase c domain", "induced helicase c domain containing", "helicase c domain containing protein", "c domain containing protein 1", "containing protein 1 ifih1", "1 ifih1 also", "ifih1 also known as", "as mda5 cervantes", "mda5 cervantes barragan", "cervantes barragan l et al.", "barragan l et al. 2007", "et al. 2007 chen", "al. 2007 chen y", "2007 chen y et", "chen y et al. 2009", "et al. 2009 2011", "2009 2011 daffis", "2011 daffis s et", "daffis s et al. 2010", "et al. 2010 li", "al. 2010 li y", "2010 li y et", "li y et al. 2013", "y et al. 2013 .", "et al. 2013 . the", "al. 2013 . the activated", "2013 . the activated prrs", ". the activated prrs trigger", "the activated prrs trigger signaling", "activated prrs trigger signaling pathways", "prrs trigger signaling pathways to", "trigger signaling pathways to produce", "signaling pathways to produce type", "pathways to produce type i", "to produce type i and", "produce type i and type", "type i and type iii", "i and type iii interferons", "and type iii interferons ifns", "type iii interferons ifns and", "iii interferons ifns and proinflammatory", "interferons ifns and proinflammatory mediators", "ifns and proinflammatory mediators that", "and proinflammatory mediators that perform", "proinflammatory mediators that perform antiviral", "mediators that perform antiviral functions.", "that perform antiviral functions. this", "perform antiviral functions. this reactome", "antiviral functions. this reactome module", "functions. this reactome module describes", "this reactome module describes the", "reactome module describes the mechanisms", "module describes the mechanisms underlying", "describes the mechanisms underlying prr", "the mechanisms underlying prr mediated", "mechanisms underlying prr mediated sensing", "underlying prr mediated sensing of", "prr mediated sensing of the", "mediated sensing of the severe", "sensing of the severe acute", "of the severe acute respiratory", "the severe acute respiratory syndrome", "severe acute respiratory syndrome coronavirus", "acute respiratory syndrome coronavirus type", "respiratory syndrome coronavirus type 1", "coronavirus type 1 sars", "type 1 sars cov", "1 sars cov 1", "sars cov 1 infection.", "cov 1 infection. first", "infection. first endosomal recognition", "first endosomal recognition of", "endosomal recognition of viral ssrna", "recognition of viral ssrna occurs", "of viral ssrna occurs by", "viral ssrna occurs by means", "ssrna occurs by means of", "occurs by means of tlr7", "by means of tlr7 and", "means of tlr7 and tlr8", "of tlr7 and tlr8 which", "tlr7 and tlr8 which detect", "and tlr8 which detect gu", "tlr8 which detect gu rich", "which detect gu rich ssrna", "detect gu rich ssrna sequences.", "gu rich ssrna sequences. specifically", "ssrna sequences. specifically gu", "sequences. specifically gu rich", "specifically gu rich ssrna", "gu rich ssrna oligonucleotides derived", "rich ssrna oligonucleotides derived from", "ssrna oligonucleotides derived from sars", "oligonucleotides derived from sars cov", "derived from sars cov 1", "from sars cov 1 stimulated", "sars cov 1 stimulated mononuclear", "cov 1 stimulated mononuclear phagocytes", "1 stimulated mononuclear phagocytes to", "stimulated mononuclear phagocytes to release", "mononuclear phagocytes to release considerable", "phagocytes to release considerable levels", "to release considerable levels of", "release considerable levels of pro\u2011inflammatory", "considerable levels of pro\u2011inflammatory cytokines", "levels of pro\u2011inflammatory cytokines tnf\u2011a", "pro\u2011inflammatory cytokines tnf\u2011a il\u20116", "cytokines tnf\u2011a il\u20116 and", "tnf\u2011a il\u20116 and il\u201112", "il\u20116 and il\u201112 via tlr7", "and il\u201112 via tlr7 and", "il\u201112 via tlr7 and tlr8", "tlr7 and tlr8 li", "and tlr8 li y", "tlr8 li y et", "et al. 2013 . second", "2013 . second sars", ". second sars cov", "second sars cov 1", "sars cov 1 dsrna replication", "cov 1 dsrna replication intermediates", "1 dsrna replication intermediates can", "dsrna replication intermediates can be", "replication intermediates can be recognized", "intermediates can be recognized by", "can be recognized by cytoplasmic", "be recognized by cytoplasmic receptors", "recognized by cytoplasmic receptors ddx58", "by cytoplasmic receptors ddx58 and", "cytoplasmic receptors ddx58 and ifih1", "receptors ddx58 and ifih1 which", "ddx58 and ifih1 which bind", "and ifih1 which bind to", "ifih1 which bind to mitochondrial", "which bind to mitochondrial antiviral", "bind to mitochondrial antiviral signaling", "to mitochondrial antiviral signaling protein", "antiviral signaling protein mavs", "protein mavs ips", "ips 1 to induce", "1 to induce the", "to induce the ifn mediated", "induce the ifn mediated antiviral", "the ifn mediated antiviral response.", "ifn mediated antiviral response. in", "mediated antiviral response. in addition", "response. in addition the", "in addition the module", "addition the module shows", "the module shows an antiviral", "module shows an antiviral function", "shows an antiviral function of", "an antiviral function of interferon", "antiviral function of interferon induced", "function of interferon induced protein", "of interferon induced protein with", "interferon induced protein with tetratricopeptide", "induced protein with tetratricopeptide repeats", "protein with tetratricopeptide repeats 1", "tetratricopeptide repeats 1 ifit1", "1 ifit1 that", "ifit1 that directly binds", "that directly binds and sequesters", "directly binds and sequesters viral", "binds and sequesters viral single", "and sequesters viral single stranded", "sequesters viral single stranded uncapped", "viral single stranded uncapped 5\u2032", "single stranded uncapped 5\u2032 ppp", "stranded uncapped 5\u2032 ppp rna", "uncapped 5\u2032 ppp rna and", "5\u2032 ppp rna and cap", "ppp rna and cap 0", "rna and cap 0 rna", "cap 0 rna daffis", "0 rna daffis s", "rna daffis s et", "s et al. 2010 .", "et al. 2010 . this", "al. 2010 . this module", "2010 . this module also", ". this module also describes", "this module also describes several", "module also describes several strategies", "also describes several strategies developed", "describes several strategies developed by", "several strategies developed by sars", "strategies developed by sars cov", "developed by sars cov 1", "by sars cov 1 to", "sars cov 1 to evade", "cov 1 to evade or", "1 to evade or alter", "to evade or alter host", "evade or alter host immunity", "alter host immunity including", "host immunity including escaping", "immunity including escaping innate", "including escaping innate immune sensors", "innate immune sensors inhibiting", "immune sensors inhibiting ifn", "sensors inhibiting ifn production", "inhibiting ifn production and signaling", "production and signaling and", "and signaling and evading", "signaling and evading antiviral", "and evading antiviral function of", "evading antiviral function of ifn", "antiviral function of ifn stimulated", "function of ifn stimulated gene", "ifn stimulated gene isg", "gene isg products.", "isg products. for example", "products. for example viral", "for example viral dsrna", "example viral dsrna replication", "viral dsrna replication intermediates derived", "dsrna replication intermediates derived from", "replication intermediates derived from sars\u2011cov\u20111", "intermediates derived from sars\u2011cov\u20111 were", "derived from sars\u2011cov\u20111 were shown", "from sars\u2011cov\u20111 were shown to", "sars\u2011cov\u20111 were shown to associate", "were shown to associate with", "shown to associate with rtc", "to associate with rtc bound", "associate with rtc bound to", "with rtc bound to double", "rtc bound to double membrane", "bound to double membrane vesicles", "double membrane vesicles which", "membrane vesicles which protected", "vesicles which protected viral", "which protected viral rna from", "protected viral rna from sensing", "viral rna from sensing by", "rna from sensing by ddx58", "from sensing by ddx58 or", "sensing by ddx58 or ifih1", "ddx58 or ifih1 stertz", "or ifih1 stertz s", "ifih1 stertz s et", "et al. 2008 . further", "2008 . further sars", ". further sars cov", "further sars cov 1", "sars cov 1 encodes nsp14", "cov 1 encodes nsp14 and", "1 encodes nsp14 and nsp16", "encodes nsp14 and nsp16 which", "nsp14 and nsp16 which possess", "and nsp16 which possess guanine", "nsp16 which possess guanine n7", "which possess guanine n7 methyltransferase", "possess guanine n7 methyltransferase activity", "guanine n7 methyltransferase activity and", "n7 methyltransferase activity and 2\u2019", "methyltransferase activity and 2\u2019 o", "activity and 2\u2019 o methyl", "and 2\u2019 o methyl transferase", "2\u2019 o methyl transferase activity", "o methyl transferase activity respectively", "transferase activity respectively chen", "activity respectively chen y", "respectively chen y et", "al. 2009 2011 .", "2009 2011 . sars", "2011 . sars cov 1", ". sars cov 1 nsp14", "sars cov 1 nsp14 generates", "cov 1 nsp14 generates 5'", "1 nsp14 generates 5' cap", "nsp14 generates 5' cap 0", "generates 5' cap 0 viral", "5' cap 0 viral rna", "0 viral rna m7gpppn", "rna m7gpppn guanine", "m7gpppn guanine n7 methylated", "guanine n7 methylated and", "n7 methylated and nsp16", "methylated and nsp16 further", "and nsp16 further methylates cap", "nsp16 further methylates cap 0", "further methylates cap 0 viral", "methylates cap 0 viral rna.", "cap 0 viral rna. these", "0 viral rna. these viral", "viral rna. these viral rna", "rna. these viral rna modifications", "these viral rna modifications mimic", "viral rna modifications mimic the", "rna modifications mimic the 5'", "modifications mimic the 5' cap", "mimic the 5' cap structure", "the 5' cap structure of", "5' cap structure of host", "cap structure of host mrnas", "structure of host mrnas allowing", "of host mrnas allowing the", "host mrnas allowing the virus", "mrnas allowing the virus to", "allowing the virus to efficiently", "the virus to efficiently evade", "virus to efficiently evade recognition", "to efficiently evade recognition by", "efficiently evade recognition by cytosolic", "evade recognition by cytosolic ddx58", "recognition by cytosolic ddx58 and", "by cytosolic ddx58 and ifih1", "ddx58 and ifih1 chen", "and ifih1 chen y", "ifih1 chen y et", "et al. 2010 . the", "al. 2010 . the nsp16", "2010 . the nsp16 mediated", ". the nsp16 mediated ribose", "the nsp16 mediated ribose 2\u2032", "nsp16 mediated ribose 2\u2032 o", "mediated ribose 2\u2032 o methylation", "ribose 2\u2032 o methylation of", "2\u2032 o methylation of viral", "o methylation of viral rna", "methylation of viral rna also", "of viral rna also blocks", "viral rna also blocks the", "rna also blocks the antiviral", "also blocks the antiviral function", "blocks the antiviral function of", "the antiviral function of ifit1", "antiviral function of ifit1 complexes", "of ifit1 complexes menachery", "ifit1 complexes menachery vd", "complexes menachery vd et", "menachery vd et al. 2014", "vd et al. 2014 .", "et al. 2014 . further", "2014 . further the", ". further the uridylate\u2010specific", "further the uridylate\u2010specific endoribonuclease", "the uridylate\u2010specific endoribonuclease endou", "endoribonuclease endou activity", "endou activity of viral", "activity of viral nsp15 degrades", "of viral nsp15 degrades viral", "viral nsp15 degrades viral rna", "nsp15 degrades viral rna to", "degrades viral rna to hide", "viral rna to hide it", "rna to hide it from", "to hide it from innate", "hide it from innate immune", "it from innate immune sensors", "innate immune sensors bhardwaj", "immune sensors bhardwaj k", "sensors bhardwaj k et", "bhardwaj k et al. 2006", "et al. 2006 ricagno", "al. 2006 ricagno s", "2006 ricagno s et", "ricagno s et al. 2006", "s et al. 2006 .", "et al. 2006 . moreover", "2006 . moreover sars", ". moreover sars cov", "moreover sars cov 1", "sars cov 1 encodes several", "cov 1 encodes several proteins", "1 encodes several proteins that", "encodes several proteins that directly", "several proteins that directly bind", "proteins that directly bind to", "that directly bind to host", "directly bind to host targets", "bind to host targets associated", "to host targets associated with", "host targets associated with sars\u2011cov\u20111", "targets associated with sars\u2011cov\u20111 infection", "associated with sars\u2011cov\u20111 infection and", "with sars\u2011cov\u20111 infection and cytokine", "sars\u2011cov\u20111 infection and cytokine production", "and cytokine production frieman", "cytokine production frieman m", "production frieman m et", "frieman m et al. 2009", "et al. 2009 hu", "al. 2009 hu y", "2009 hu y et", "hu y et al. 2017", "et al. 2017 kopecky", "al. 2017 kopecky bromberg", "2017 kopecky bromberg sa", "kopecky bromberg sa et al.", "bromberg sa et al. 2007", "et al. 2007 lindner", "al. 2007 lindner h", "2007 lindner h et", "lindner h et al. 2005", "et al. 2005 siu", "al. 2005 siu kl", "2005 siu kl et", "siu kl et al. 2009", "kl et al. 2009 .", "et al. 2009 . this", "al. 2009 . this reactome", "2009 . this reactome module", ". this reactome module describes", "this reactome module describes several", "reactome module describes several such", "module describes several such binding", "describes several such binding events", "several such binding events and", "such binding events and their", "binding events and their consequences.", "events and their consequences. for", "and their consequences. for example", "consequences. for example as", "for example as a", "example as a de", "as a de ubiquitinating enzyme", "de ubiquitinating enzyme viral", "ubiquitinating enzyme viral nsp3", "enzyme viral nsp3 binds", "viral nsp3 binds to and", "nsp3 binds to and removes", "binds to and removes polyubiquitin", "to and removes polyubiquitin chains", "and removes polyubiquitin chains of", "removes polyubiquitin chains of signaling", "polyubiquitin chains of signaling proteins", "chains of signaling proteins such", "of signaling proteins such as", "signaling proteins such as traf3", "such as traf3 traf6", "traf3 traf6 sting", "traf6 sting ikba", "sting ikba and", "ikba and irf3 thereby", "and irf3 thereby modulating the", "irf3 thereby modulating the formation", "thereby modulating the formation of", "modulating the formation of signaling", "the formation of signaling complexes", "formation of signaling complexes and", "of signaling complexes and the", "signaling complexes and the activation", "complexes and the activation of", "and the activation of irf3/7", "the activation of irf3/7 and", "activation of irf3/7 and nfkappab", "irf3/7 and nfkappab sun", "and nfkappab sun l", "nfkappab sun l et", "sun l et al. 2012", "et al. 2012 chen", "al. 2012 chen x", "2012 chen x et", "chen x et al. 2014", "et al. 2014 li", "al. 2014 li sw", "2014 li sw et", "li sw et al. 2016", "sw et al. 2016 .", "et al. 2016 . this", "al. 2016 . this inhibits", "2016 . this inhibits ifn", ". this inhibits ifn production", "this inhibits ifn production downstream", "inhibits ifn production downstream of", "ifn production downstream of tlr7/8", "downstream of tlr7/8 ddx58", "tlr7/8 ddx58 ifih1", "ddx58 ifih1 mavs", "ifih1 mavs and sting", "mavs and sting signaling pathways.", "and sting signaling pathways. binding", "sting signaling pathways. binding of", "signaling pathways. binding of sars", "pathways. binding of sars cov", "binding of sars cov 1", "of sars cov 1 nucleocapsid", "cov 1 nucleocapsid n", "nucleocapsid n protein", "n protein to e3", "protein to e3 ubiquitin ligase", "to e3 ubiquitin ligase trim25", "e3 ubiquitin ligase trim25 inhibits", "ubiquitin ligase trim25 inhibits trim25", "ligase trim25 inhibits trim25 mediated", "trim25 inhibits trim25 mediated ddx58", "inhibits trim25 mediated ddx58 ubiquitination", "trim25 mediated ddx58 ubiquitination and", "mediated ddx58 ubiquitination and ddx58", "ddx58 ubiquitination and ddx58 mediated", "ubiquitination and ddx58 mediated signaling", "and ddx58 mediated signaling pathway", "mediated signaling pathway hu", "signaling pathway hu y", "pathway hu y et", "y et al. 2017 .", "et al. 2017 . next", "2017 . next sars\u2011cov\u20111", ". next sars\u2011cov\u20111 membrane", "membrane m protein", "m protein targets ibk1/ikbke", "protein targets ibk1/ikbke and traf3", "targets ibk1/ikbke and traf3 to", "ibk1/ikbke and traf3 to prevent", "and traf3 to prevent the", "traf3 to prevent the formation", "to prevent the formation of", "prevent the formation of the", "the formation of the traf3:tank:tbk1/ikbke", "formation of the traf3:tank:tbk1/ikbke complex", "of the traf3:tank:tbk1/ikbke complex and", "the traf3:tank:tbk1/ikbke complex and thereby", "traf3:tank:tbk1/ikbke complex and thereby inhibits", "complex and thereby inhibits tbk1/ikbke\u2011dependent", "and thereby inhibits tbk1/ikbke\u2011dependent activation", "thereby inhibits tbk1/ikbke\u2011dependent activation of", "inhibits tbk1/ikbke\u2011dependent activation of irf3/irf7", "tbk1/ikbke\u2011dependent activation of irf3/irf7 transcription", "activation of irf3/irf7 transcription factors", "of irf3/irf7 transcription factors downstream", "irf3/irf7 transcription factors downstream of", "transcription factors downstream of ddx58", "downstream of ddx58 ifih1", "of ddx58 ifih1 and", "ddx58 ifih1 and adaptor", "and adaptor mavs siu", "adaptor mavs siu kl", "mavs siu kl et", "et al. 2009 2014", "al. 2009 2014 .", "2009 2014 . the", "2014 . the ion channel", ". the ion channel activities", "the ion channel activities of", "ion channel activities of open", "channel activities of open reading", "activities of open reading frame", "of open reading frame 3a", "reading frame 3a orf3a", "frame 3a orf3a or", "3a orf3a or 3a", "orf3a or 3a and", "or 3a and e", "3a and e contribute", "and e contribute to activation", "e contribute to activation of", "contribute to activation of the", "to activation of the nlrp3", "activation of the nlrp3 inflammasome", "of the nlrp3 inflammasome leading", "the nlrp3 inflammasome leading to", "nlrp3 inflammasome leading to highly", "inflammasome leading to highly inflammatory", "leading to highly inflammatory pyroptotic", "to highly inflammatory pyroptotic cell", "highly inflammatory pyroptotic cell death", "pyroptotic cell death nieto\u2011torres", "cell death nieto\u2011torres jl", "death nieto\u2011torres jl et", "nieto\u2011torres jl et al. 2015", "et al. 2015 chen", "al. 2015 chen iy", "2015 chen iy et", "chen iy et al. 2019", "et al. 2019 yue", "al. 2019 yue y", "2019 yue y et", "yue y et al. 2018", "y et al. 2018 .", "et al. 2018 . viral", "al. 2018 . viral 3a", "2018 . viral 3a promoted", ". viral 3a promoted the", "viral 3a promoted the nlrp3", "3a promoted the nlrp3 mediated", "promoted the nlrp3 mediated formation", "the nlrp3 mediated formation of", "nlrp3 mediated formation of pycard", "formation of pycard asc", "pycard asc speck", "asc speck by interaction", "speck by interaction with both", "by interaction with both traf3", "interaction with both traf3 and", "with both traf3 and pycard", "traf3 and pycard asc", "asc siu kl", "siu kl et al. 2019", "kl et al. 2019 .", "et al. 2019 . binding", "al. 2019 . binding of", "2019 . binding of 3a", ". binding of 3a to", "binding of 3a to caspase", "of 3a to caspase 1", "to caspase 1 casp1", "1 casp1 enhanced", "casp1 enhanced casp1 mediated", "enhanced casp1 mediated cleavage of", "casp1 mediated cleavage of interleukin", "mediated cleavage of interleukin 1", "cleavage of interleukin 1 beta", "interleukin 1 beta il\u20111\u03b2", "beta il\u20111\u03b2 downstream", "il\u20111\u03b2 downstream of the", "downstream of the nlrp3 inflammasome", "of the nlrp3 inflammasome pathway", "nlrp3 inflammasome pathway yue", "inflammasome pathway yue y", "pathway yue y et", "et al. 2018 . like", "al. 2018 . like 3a", ". like 3a sars", "like 3a sars cov", "3a sars cov 1", "sars cov 1 8b was", "cov 1 8b was found", "1 8b was found to", "8b was found to bind", "was found to bind to", "found to bind to nlrp3", "to bind to nlrp3 activating", "bind to nlrp3 activating the", "to nlrp3 activating the nlrp3", "nlrp3 activating the nlrp3 inflammasome", "activating the nlrp3 inflammasome and", "the nlrp3 inflammasome and triggering", "nlrp3 inflammasome and triggering il\u20111\u03b2", "inflammasome and triggering il\u20111\u03b2 release", "triggering il\u20111\u03b2 release shi", "il\u20111\u03b2 release shi cs", "release shi cs et", "shi cs et al. 2019", "cs et al. 2019 .", "et al. 2019 . 8b", "al. 2019 . 8b was", "2019 . 8b was also", ". 8b was also shown", "8b was also shown to", "was also shown to bind", "also shown to bind irf3", "to bind irf3 inhibiting", "bind irf3 inhibiting subsequent", "irf3 inhibiting subsequent irf3", "subsequent irf3 dimerization wong", "irf3 dimerization wong et", "dimerization wong et al.", "wong et al. 2018 .", "et al. 2018 . at", "al. 2018 . at the", "2018 . at the plasma", ". at the plasma membrane", "the plasma membrane binding", "plasma membrane binding of", "membrane binding of sars", "of sars cov 1 7a", "sars cov 1 7a to", "cov 1 7a to host", "1 7a to host bst2", "7a to host bst2 disrupts", "to host bst2 disrupts the", "host bst2 disrupts the antiviral", "bst2 disrupts the antiviral tethering", "disrupts the antiviral tethering function", "the antiviral tethering function of", "antiviral tethering function of bst2", "tethering function of bst2 which", "function of bst2 which restricts", "of bst2 which restricts the", "bst2 which restricts the release", "which restricts the release of", "restricts the release of diverse", "the release of diverse mammalian", "release of diverse mammalian enveloped", "of diverse mammalian enveloped viruses", "mammalian enveloped viruses taylor", "enveloped viruses taylor jk", "viruses taylor jk et", "taylor jk et al. 2015", "jk et al. 2015 .", "et al. 2015 . sars", "al. 2015 . sars cov", "2015 . sars cov 1", ". sars cov 1 9b", "cov 1 9b orf9b", "9b orf9b inhibits", "orf9b inhibits the mavs", "inhibits the mavs mediated production", "the mavs mediated production of", "mavs mediated production of type", "mediated production of type i", "production of type i ifns", "of type i ifns by", "type i ifns by targeting", "i ifns by targeting tomm70", "ifns by targeting tomm70 on", "by targeting tomm70 on the", "targeting tomm70 on the mitochondria", "on the mitochondria jiang", "the mitochondria jiang hw", "mitochondria jiang hw et", "jiang hw et al. 2020", "hw et al. 2020 .", "et al. 2020 . sars", "al. 2020 . sars cov", "2020 . sars cov 1", ". sars cov 1 6", "cov 1 6 orf6", "6 orf6 inhibits", "orf6 inhibits the ifn", "inhibits the ifn signaling pathway", "the ifn signaling pathway by", "ifn signaling pathway by tethering", "signaling pathway by tethering karyopherins", "pathway by tethering karyopherins kpna2", "by tethering karyopherins kpna2 and", "tethering karyopherins kpna2 and kpnb1", "karyopherins kpna2 and kpnb1 to", "kpna2 and kpnb1 to the", "and kpnb1 to the endoplasmic", "kpnb1 to the endoplasmic reticulum", "the endoplasmic reticulum er", "endoplasmic reticulum er /golgi", "reticulum er /golgi intermediate", "/golgi intermediate compartment ergic", "compartment ergic and", "ergic and thus blocking", "and thus blocking the kpna1:kpnb1", "thus blocking the kpna1:kpnb1 dependent", "blocking the kpna1:kpnb1 dependent nuclear", "the kpna1:kpnb1 dependent nuclear import", "kpna1:kpnb1 dependent nuclear import of", "dependent nuclear import of stat1", "import of stat1 frieman", "of stat1 frieman m", "stat1 frieman m et", "frieman m et al. 2007", "m et al. 2007 .", "et al. 2007 . binding", "al. 2007 . binding of", "2007 . binding of sars", ". binding of sars cov", "of sars cov 1 nsp1", "sars cov 1 nsp1 to", "cov 1 nsp1 to peptidyl", "1 nsp1 to peptidyl prolyl", "nsp1 to peptidyl prolyl isomerases", "peptidyl prolyl isomerases ppiases", "isomerases ppiases and", "ppiases and calcipressin 3", "and calcipressin 3 rcan3", "3 rcan3 significantly", "rcan3 significantly activates the", "significantly activates the cyclophilin a/nfat", "activates the cyclophilin a/nfat pathway", "cyclophilin a/nfat pathway ultimately", "a/nfat pathway ultimately enhancing", "pathway ultimately enhancing the", "ultimately enhancing the induction of", "enhancing the induction of the", "the induction of the il", "induction of the il 2", "of the il 2 promoter", "il 2 promoter pfefferle", "2 promoter pfefferle et", "promoter pfefferle et al", "pfefferle et al 2011", "al 2011 law", "2011 law et al", "law et al 2007", "et al 2007 .", "al 2007 . at", ". at last sars\u2011cov\u20111", "at last sars\u2011cov\u20111 3b", "sars\u2011cov\u20111 3b after translocating", "3b after translocating to", "after translocating to the nucleus", "to the nucleus binds", "the nucleus binds to", "nucleus binds to transcription", "binds to transcription factor runx1", "to transcription factor runx1 and", "transcription factor runx1 and increases", "factor runx1 and increases its", "runx1 and increases its promoting", "and increases its promoting activity", "its promoting activity varshney", "promoting activity varshney et", "activity varshney et al", "varshney et al 2012", "et al 2012 ." ] }, { "record_id": "GLY_000594_1_2063", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9735871", "r hsa", "hsa 9735871", "r hsa 9735871" ] }, { "record_id": "GLY_000594_1_2063", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 1", "1 targets", "targets host", "host intracellular", "intracellular signalling", "signalling and", "and regulatory", "regulatory pathways", "sars cov 1", "cov 1 targets", "1 targets host", "targets host intracellular", "host intracellular signalling", "intracellular signalling and", "signalling and regulatory", "and regulatory pathways", "sars cov 1 targets", "cov 1 targets host", "1 targets host intracellular", "targets host intracellular signalling", "host intracellular signalling and", "intracellular signalling and regulatory", "signalling and regulatory pathways", "sars cov 1 targets host", "cov 1 targets host intracellular", "1 targets host intracellular signalling", "targets host intracellular signalling and", "host intracellular signalling and regulatory", "intracellular signalling and regulatory pathways", "severe acute", "acute respiratory", "respiratory syndrome", "syndrome coronavirus", "coronavirus type", "type 1", "encodes several", "several proteins", "proteins that", "that modulate", "modulate host", "intracellular signaling", "signaling and", "regulatory pathways.", "pathways. among", "among them", "them are", "are nucleocapsid", "nucleocapsid n", "membrane m", "m and", "and 3a", "3a proteins", "that directly", "directly bind", "bind to", "to host", "host targets", "targets associated", "associated with", "with sars\u2011cov\u20111", "sars\u2011cov\u20111 infection", "infection and", "and cytokine", "cytokine production.", "production. this", "this reactome", "reactome module", "module describes", "describes several", "several such", "such binding", "binding events", "events and", "and their", "their consequences.", "consequences. first", "sars\u2011cov\u20111 m", "m binds", "binds to", "to 3\u2011phosphoinositide\u2011dependent", "3\u2011phosphoinositide\u2011dependent protein", "protein kinase", "kinase 1", "to inhibit", "inhibit pkb/akt", "pkb/akt activation", "chan et", "et al.", "al. 2007", "tsoi et", "al. 2014", "2014 .", ". second", "sars\u2011cov\u20111 n", "n binds", "to smad3", "smad3 to", "to alter", "alter transforming", "transforming growth", "growth factor\u2011\u03b2", "zhao et", "al. 2008", "2008 .", ". this", "this interaction", "interaction prevents", "prevents smad3", "smad3 from", "from complexing", "complexing with", "with smad4", "thereby blocking", "blocking tgf", "tgf \u03b2", "\u03b2 sensitized", "sensitized apoptosis.", "apoptosis. the", "the association", "association of", "of n", "n with", "with smad3", "smad3 also", "also enhances", "enhances the", "the tgf", "\u03b2 induced", "induced expression", "expression of", "of pai", "pai 1", "promoting tissue", "tissue fibrosis", ". third", "n protein", "protein binding", "binding to", "to proteasome", "proteasome subunit", "subunit p42", "modulates proteasome\u2011regulated", "proteasome\u2011regulated degradation", "degradation of", "of proteins", "wang et", "al. 2010", "2010 .", ". fourth", "binds sumo", "sumo conjugating", "conjugating enzyme", "enzyme ubc9", "to regulate", "regulate the", "the activity", "activity of", "of ube2i", "affecting downstream", "downstream signaling", "signaling factors", "factors involved", "involved in", "in the", "the cell", "cell cycle", "in addition", "addition to", "to its", "its function", "function in", "the process", "process of", "of sumoylation", "fan et", "al. 2006", "2006 .", ". finally", "binding of", "of viral", "viral 3a", "3a to", "to the", "the regulator", "regulator and", "and scaffolding", "scaffolding protein", "protein caveolin\u20111", "may regulate", "regulate virus", "virus uptake", "uptake as", "as well", "well as", "as the", "the trafficking", "trafficking of", "viral structural", "structural proteins", "padhan et", "2007 .", "severe acute respiratory", "acute respiratory syndrome", "respiratory syndrome coronavirus", "syndrome coronavirus type", "coronavirus type 1", "1 sars\u2011cov\u20111", "sars\u2011cov\u20111 encodes", "encodes several proteins", "several proteins that", "proteins that modulate", "that modulate host", "modulate host intracellular", "host intracellular signaling", "intracellular signaling and", "signaling and regulatory", "and regulatory pathways.", "regulatory pathways. among", "pathways. among them", "among them are", "them are nucleocapsid", "are nucleocapsid n", "n membrane", "membrane m and", "m and 3a", "and 3a proteins", "3a proteins that", "proteins that directly", "that directly bind", "directly bind to", "bind to host", "to host targets", "host targets associated", "targets associated with", "associated with sars\u2011cov\u20111", "with sars\u2011cov\u20111 infection", "sars\u2011cov\u20111 infection and", "infection and cytokine", "and cytokine production.", "cytokine production. this", "production. this reactome", "this reactome module", "reactome module describes", "module describes several", "describes several such", "several such binding", "such binding events", "binding events and", "events and their", "and their consequences.", "their consequences. first", "first sars\u2011cov\u20111", "sars\u2011cov\u20111 m binds", "m binds to", "binds to 3\u2011phosphoinositide\u2011dependent", "to 3\u2011phosphoinositide\u2011dependent protein", "3\u2011phosphoinositide\u2011dependent protein kinase", "protein kinase 1", "1 pdpk1", "pdpk1 to", "to inhibit pkb/akt", "inhibit pkb/akt activation", "activation chan", "chan et al.", "et al. 2007", "2007 tsoi", "tsoi et al.", "et al. 2014", "al. 2014 .", "2014 . second", "second sars\u2011cov\u20111", "sars\u2011cov\u20111 n binds", "n binds to", "binds to smad3", "to smad3 to", "smad3 to alter", "to alter transforming", "alter transforming growth", "transforming growth factor\u2011\u03b2", "factor\u2011\u03b2 tgf\u2011\u03b2", "tgf\u2011\u03b2 signaling", "signaling zhao", "zhao et al.", "et al. 2008", "al. 2008 .", "2008 . this", ". this interaction", "this interaction prevents", "interaction prevents smad3", "prevents smad3 from", "smad3 from complexing", "from complexing with", "complexing with smad4", "smad4 thereby", "thereby blocking tgf", "blocking tgf \u03b2", "tgf \u03b2 sensitized", "\u03b2 sensitized apoptosis.", "sensitized apoptosis. the", "apoptosis. the association", "the association of", "association of n", "of n with", "n with smad3", "with smad3 also", "smad3 also enhances", "also enhances the", "enhances the tgf", "the tgf \u03b2", "tgf \u03b2 induced", "\u03b2 induced expression", "induced expression of", "expression of pai", "of pai 1", "1 serpine1", "serpine1 promoting", "promoting tissue fibrosis", "fibrosis zhao", "2008 . third", "third n", "n protein binding", "protein binding to", "binding to proteasome", "to proteasome subunit", "proteasome subunit p42", "p42 psmc6", "psmc6 modulates", "modulates proteasome\u2011regulated degradation", "proteasome\u2011regulated degradation of", "degradation of proteins", "proteins wang", "wang et al.", "et al. 2010", "al. 2010 .", "2010 . fourth", "fourth sars\u2011cov\u20111", "n binds sumo", "binds sumo conjugating", "sumo conjugating enzyme", "conjugating enzyme ubc9", "ubc9 ube2i", "ube2i to", "to regulate the", "regulate the activity", "the activity of", "activity of ube2i", "ube2i affecting", "affecting downstream signaling", "downstream signaling factors", "signaling factors involved", "factors involved in", "involved in the", "in the cell", "the cell cycle", "cycle in", "in addition to", "addition to its", "to its function", "its function in", "function in the", "in the process", "the process of", "process of sumoylation", "sumoylation fan", "fan et al.", "et al. 2006", "al. 2006 .", "2006 . finally", "finally binding", "binding of viral", "of viral 3a", "viral 3a to", "3a to the", "to the regulator", "the regulator and", "regulator and scaffolding", "and scaffolding protein", "scaffolding protein caveolin\u20111", "caveolin\u20111 cav1", "cav1 may", "may regulate virus", "regulate virus uptake", "virus uptake as", "uptake as well", "as well as", "well as the", "as the trafficking", "the trafficking of", "trafficking of viral", "of viral structural", "viral structural proteins", "proteins padhan", "padhan et al.", "al. 2007 .", "severe acute respiratory syndrome", "acute respiratory syndrome coronavirus", "respiratory syndrome coronavirus type", "syndrome coronavirus type 1", "type 1 sars\u2011cov\u20111", "sars\u2011cov\u20111 encodes several", "encodes several proteins that", "several proteins that modulate", "proteins that modulate host", "that modulate host intracellular", "modulate host intracellular signaling", "host intracellular signaling and", "intracellular signaling and regulatory", "signaling and regulatory pathways.", "and regulatory pathways. among", "regulatory pathways. among them", "pathways. among them are", "among them are nucleocapsid", "them are nucleocapsid n", "nucleocapsid n membrane", "n membrane m", "membrane m and 3a", "m and 3a proteins", "and 3a proteins that", "3a proteins that directly", "proteins that directly bind", "that directly bind to", "directly bind to host", "bind to host targets", "to host targets associated", "host targets associated with", "targets associated with sars\u2011cov\u20111", "associated with sars\u2011cov\u20111 infection", "with sars\u2011cov\u20111 infection and", "sars\u2011cov\u20111 infection and cytokine", "infection and cytokine production.", "and cytokine production. this", "cytokine production. this reactome", "production. this reactome module", "this reactome module describes", "reactome module describes several", "module describes several such", "describes several such binding", "several such binding events", "such binding events and", "binding events and their", "events and their consequences.", "and their consequences. first", "consequences. first sars\u2011cov\u20111", "first sars\u2011cov\u20111 m", "sars\u2011cov\u20111 m binds to", "m binds to 3\u2011phosphoinositide\u2011dependent", "binds to 3\u2011phosphoinositide\u2011dependent protein", "to 3\u2011phosphoinositide\u2011dependent protein kinase", "3\u2011phosphoinositide\u2011dependent protein kinase 1", "kinase 1 pdpk1", "pdpk1 to inhibit", "to inhibit pkb/akt activation", "pkb/akt activation chan", "activation chan et", "chan et al. 2007", "al. 2007 tsoi", "2007 tsoi et", "tsoi et al. 2014", "et al. 2014 .", "al. 2014 . second", ". second sars\u2011cov\u20111", "second sars\u2011cov\u20111 n", "sars\u2011cov\u20111 n binds to", "n binds to smad3", "binds to smad3 to", "to smad3 to alter", "smad3 to alter transforming", "to alter transforming growth", "alter transforming growth factor\u2011\u03b2", "growth factor\u2011\u03b2 tgf\u2011\u03b2", "signaling zhao et", "zhao et al. 2008", "et al. 2008 .", "al. 2008 . this", "2008 . this interaction", ". this interaction prevents", "this interaction prevents smad3", "interaction prevents smad3 from", "prevents smad3 from complexing", "smad3 from complexing with", "from complexing with smad4", "with smad4 thereby", "smad4 thereby blocking", "thereby blocking tgf \u03b2", "blocking tgf \u03b2 sensitized", "tgf \u03b2 sensitized apoptosis.", "\u03b2 sensitized apoptosis. the", "sensitized apoptosis. the association", "apoptosis. the association of", "the association of n", "association of n with", "of n with smad3", "n with smad3 also", "with smad3 also enhances", "smad3 also enhances the", "also enhances the tgf", "enhances the tgf \u03b2", "the tgf \u03b2 induced", "tgf \u03b2 induced expression", "\u03b2 induced expression of", "induced expression of pai", "expression of pai 1", "pai 1 serpine1", "serpine1 promoting tissue", "tissue fibrosis zhao", "fibrosis zhao et", "al. 2008 . third", ". third n", "third n protein", "n protein binding to", "protein binding to proteasome", "binding to proteasome subunit", "to proteasome subunit p42", "subunit p42 psmc6", "psmc6 modulates proteasome\u2011regulated", "modulates proteasome\u2011regulated degradation of", "proteasome\u2011regulated degradation of proteins", "of proteins wang", "proteins wang et", "wang et al. 2010", "et al. 2010 .", "al. 2010 . fourth", ". fourth sars\u2011cov\u20111", "fourth sars\u2011cov\u20111 n", "sars\u2011cov\u20111 n binds sumo", "n binds sumo conjugating", "binds sumo conjugating enzyme", "sumo conjugating enzyme ubc9", "enzyme ubc9 ube2i", "ube2i to regulate", "to regulate the activity", "regulate the activity of", "the activity of ube2i", "of ube2i affecting", "ube2i affecting downstream", "affecting downstream signaling factors", "downstream signaling factors involved", "signaling factors involved in", "factors involved in the", "involved in the cell", "in the cell cycle", "cell cycle in", "cycle in addition", "in addition to its", "addition to its function", "to its function in", "its function in the", "function in the process", "in the process of", "the process of sumoylation", "of sumoylation fan", "sumoylation fan et", "fan et al. 2006", "et al. 2006 .", "al. 2006 . finally", ". finally binding", "finally binding of", "binding of viral 3a", "of viral 3a to", "viral 3a to the", "3a to the regulator", "to the regulator and", "the regulator and scaffolding", "regulator and scaffolding protein", "and scaffolding protein caveolin\u20111", "protein caveolin\u20111 cav1", "cav1 may regulate", "may regulate virus uptake", "regulate virus uptake as", "virus uptake as well", "uptake as well as", "as well as the", "well as the trafficking", "as the trafficking of", "the trafficking of viral", "trafficking of viral structural", "of viral structural proteins", "structural proteins padhan", "proteins padhan et", "padhan et al. 2007", "et al. 2007 .", "severe acute respiratory syndrome coronavirus", "acute respiratory syndrome coronavirus type", "respiratory syndrome coronavirus type 1", "coronavirus type 1 sars\u2011cov\u20111", "1 sars\u2011cov\u20111 encodes", "sars\u2011cov\u20111 encodes several proteins", "encodes several proteins that modulate", "several proteins that modulate host", "proteins that modulate host intracellular", "that modulate host intracellular signaling", "modulate host intracellular signaling and", "host intracellular signaling and regulatory", "intracellular signaling and regulatory pathways.", "signaling and regulatory pathways. among", "and regulatory pathways. among them", "regulatory pathways. among them are", "pathways. among them are nucleocapsid", "among them are nucleocapsid n", "are nucleocapsid n membrane", "nucleocapsid n membrane m", "n membrane m and", "membrane m and 3a proteins", "m and 3a proteins that", "and 3a proteins that directly", "3a proteins that directly bind", "proteins that directly bind to", "that directly bind to host", "directly bind to host targets", "bind to host targets associated", "to host targets associated with", "host targets associated with sars\u2011cov\u20111", "targets associated with sars\u2011cov\u20111 infection", "associated with sars\u2011cov\u20111 infection and", "with sars\u2011cov\u20111 infection and cytokine", "sars\u2011cov\u20111 infection and cytokine production.", "infection and cytokine production. this", "and cytokine production. this reactome", "cytokine production. this reactome module", "production. this reactome module describes", "this reactome module describes several", "reactome module describes several such", "module describes several such binding", "describes several such binding events", "several such binding events and", "such binding events and their", "binding events and their consequences.", "events and their consequences. first", "their consequences. first sars\u2011cov\u20111", "consequences. first sars\u2011cov\u20111 m", "first sars\u2011cov\u20111 m binds", "sars\u2011cov\u20111 m binds to 3\u2011phosphoinositide\u2011dependent", "m binds to 3\u2011phosphoinositide\u2011dependent protein", "binds to 3\u2011phosphoinositide\u2011dependent protein kinase", "to 3\u2011phosphoinositide\u2011dependent protein kinase 1", "protein kinase 1 pdpk1", "1 pdpk1 to", "pdpk1 to inhibit pkb/akt", "inhibit pkb/akt activation chan", "pkb/akt activation chan et", "activation chan et al.", "et al. 2007 tsoi", "al. 2007 tsoi et", "2007 tsoi et al.", "tsoi et al. 2014 .", "et al. 2014 . second", "2014 . second sars\u2011cov\u20111", ". second sars\u2011cov\u20111 n", "second sars\u2011cov\u20111 n binds", "sars\u2011cov\u20111 n binds to smad3", "n binds to smad3 to", "binds to smad3 to alter", "to smad3 to alter transforming", "smad3 to alter transforming growth", "to alter transforming growth factor\u2011\u03b2", "transforming growth factor\u2011\u03b2 tgf\u2011\u03b2", "factor\u2011\u03b2 tgf\u2011\u03b2 signaling", "tgf\u2011\u03b2 signaling zhao", "signaling zhao et al.", "zhao et al. 2008 .", "et al. 2008 . this", "al. 2008 . this interaction", "2008 . this interaction prevents", ". this interaction prevents smad3", "this interaction prevents smad3 from", "interaction prevents smad3 from complexing", "prevents smad3 from complexing with", "smad3 from complexing with smad4", "complexing with smad4 thereby", "with smad4 thereby blocking", "smad4 thereby blocking tgf", "thereby blocking tgf \u03b2 sensitized", "blocking tgf \u03b2 sensitized apoptosis.", "tgf \u03b2 sensitized apoptosis. the", "\u03b2 sensitized apoptosis. the association", "sensitized apoptosis. the association of", "apoptosis. the association of n", "the association of n with", "association of n with smad3", "of n with smad3 also", "n with smad3 also enhances", "with smad3 also enhances the", "smad3 also enhances the tgf", "also enhances the tgf \u03b2", "enhances the tgf \u03b2 induced", "the tgf \u03b2 induced expression", "tgf \u03b2 induced expression of", "\u03b2 induced expression of pai", "induced expression of pai 1", "of pai 1 serpine1", "1 serpine1 promoting", "serpine1 promoting tissue fibrosis", "promoting tissue fibrosis zhao", "tissue fibrosis zhao et", "fibrosis zhao et al.", "et al. 2008 . third", "2008 . third n", ". third n protein", "third n protein binding", "n protein binding to proteasome", "protein binding to proteasome subunit", "binding to proteasome subunit p42", "proteasome subunit p42 psmc6", "p42 psmc6 modulates", "psmc6 modulates proteasome\u2011regulated degradation", "modulates proteasome\u2011regulated degradation of proteins", "degradation of proteins wang", "of proteins wang et", "proteins wang et al.", "wang et al. 2010 .", "et al. 2010 . fourth", "2010 . fourth sars\u2011cov\u20111", ". fourth sars\u2011cov\u20111 n", "fourth sars\u2011cov\u20111 n binds", "sars\u2011cov\u20111 n binds sumo conjugating", "n binds sumo conjugating enzyme", "binds sumo conjugating enzyme ubc9", "conjugating enzyme ubc9 ube2i", "ubc9 ube2i to", "ube2i to regulate the", "to regulate the activity of", "regulate the activity of ube2i", "activity of ube2i affecting", "of ube2i affecting downstream", "ube2i affecting downstream signaling", "affecting downstream signaling factors involved", "downstream signaling factors involved in", "signaling factors involved in the", "factors involved in the cell", "involved in the cell cycle", "the cell cycle in", "cell cycle in addition", "cycle in addition to", "in addition to its function", "addition to its function in", "to its function in the", "its function in the process", "function in the process of", "in the process of sumoylation", "process of sumoylation fan", "of sumoylation fan et", "sumoylation fan et al.", "fan et al. 2006 .", "et al. 2006 . finally", "2006 . finally binding", ". finally binding of", "finally binding of viral", "binding of viral 3a to", "of viral 3a to the", "viral 3a to the regulator", "3a to the regulator and", "to the regulator and scaffolding", "the regulator and scaffolding protein", "regulator and scaffolding protein caveolin\u20111", "scaffolding protein caveolin\u20111 cav1", "caveolin\u20111 cav1 may", "cav1 may regulate virus", "may regulate virus uptake as", "regulate virus uptake as well", "virus uptake as well as", "uptake as well as the", "as well as the trafficking", "well as the trafficking of", "as the trafficking of viral", "the trafficking of viral structural", "trafficking of viral structural proteins", "viral structural proteins padhan", "structural proteins padhan et", "proteins padhan et al.", "padhan et al. 2007 ." ] }, { "record_id": "GLY_000594_1_2064", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9758919", "r hsa", "hsa 9758919", "r hsa 9758919" ] }, { "record_id": "GLY_000594_1_2064", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "epithelial mesenchymal", "mesenchymal transition", "during gastrulation", "epithelial mesenchymal transition", "transition emt", "emt during", "mesenchymal transition emt", "emt during 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embryos", "embryos in", "in ciruna", "ciruna and", "and rossant", "rossant 2001", "2001 .", ". in", "in later", "later stage", "stage cancer", "cancer cells", "cells the", "the tgfbeta", "tgfbeta signaling", "signaling pathway", "pathway is", "is a", "a major", "major inducer", "inducer of", "emt that", "that leads", "leads to", "to metastasis", "in hao", "hao et", "et al.", "al. 2019", "2019 .", ". during", "gastrulation bmp4", "bmp4 and", "and nodal", "nodal of", "tgfbeta pathways", "pathways are", "are also", "also probably", "probably involved", "involved in", "in emt", "martyn et", "al. 2018", "2018 .
              this", ".
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              this", "2018 .
              this epithelial", ".
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              snail", ".
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"which promotes cell", "promotes cell ingression", "ingression inferred", "homologs in ramkumar", "in ramkumar et", "ramkumar et al.", "et al. 2016", "rhoa and microtubules", "microtubules which", "which control cell", "control cell basement", "cell basement interactions", "interactions inferred", "homologs in nakaya", "in nakaya et", "nakaya et al.", "and p38 and", "p38 and p38", "and p38 interacting", "p38 interacting protein", "protein which", "which are critical", "are critical for", "critical for downregulating", "for downregulating e", "downregulating e cadherin", "cadherin zohn", "zohn et al.", "et al. 2006", "al. 2006 .", "during the epithelial mesenchymal", "the epithelial mesenchymal transition", "during gastrulation epithelial", "gastrulation epithelial cells", "epithelial cells in the", "cells in the primitive", "in the primitive streak", "the primitive streak transition", "primitive streak transition to", "streak transition to dissociated", "transition to dissociated 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              this", "al. 2018 .
              this epithelial", "2018 .
              this epithelial mesenchymal", ".
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              snail", "2014 .
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embryo reviewed in", "embryo reviewed in morgani", "reviewed in morgani and hadjantonakis", "in morgani and hadjantonakis 2021", "morgani and hadjantonakis 2021 .", "and hadjantonakis 2021 . the", "hadjantonakis 2021 . the fgf", "2021 . the fgf pathway", ". the fgf pathway in", "the fgf pathway in particular", "fgf pathway in particular has", "pathway in particular has been", "in particular has been implicated", "particular has been implicated in", "has been implicated in the", "been implicated in the regulation", "implicated in the regulation of", "in the regulation of emt", "the regulation of emt during", "regulation of emt during gastrulation", "emt during gastrulation inferred", "during gastrulation inferred from", "gastrulation inferred from mouse", "inferred from mouse embryos in", "from mouse embryos in ciruna", "mouse embryos in ciruna and", "embryos in ciruna and rossant", "in ciruna and rossant 2001", "ciruna and rossant 2001 .", "and rossant 2001 . in", "rossant 2001 . in later", "2001 . in later stage", ". in later stage cancer", "in later stage cancer cells", "later stage cancer cells the", "stage cancer cells the tgfbeta", "cancer cells the tgfbeta signaling", "cells the tgfbeta signaling pathway", "the tgfbeta signaling pathway is", "tgfbeta signaling pathway is a", "signaling pathway is a major", "pathway is a major inducer", "is a major inducer of", "a major inducer of emt", "major inducer of emt that", "inducer of emt that leads", "of emt that leads to", "emt that leads to metastasis", "leads to metastasis reviewed", "to metastasis reviewed in", "metastasis reviewed in hao", "reviewed in hao et al.", "in hao et al. 2019", "hao et al. 2019 .", "et al. 2019 . during", "al. 2019 . during gastrulation", "2019 . during gastrulation bmp4", ". during gastrulation bmp4 and", "during gastrulation bmp4 and nodal", "gastrulation bmp4 and nodal of", "bmp4 and nodal of the", "and nodal of the tgfbeta", "nodal of the tgfbeta pathways", "of the tgfbeta pathways 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              this", "et al. 2018 .
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              cipro is", ".

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              very", ".

              very high", "

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              cipro", "2020 .

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              very high", ".

              very high concentrations", "

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usual", "cns effects. the usual dosages", "effects. the usual dosages are", "the usual dosages are 250", "usual dosages are 250 mg", "dosages are 250 mg and", "are 250 mg and 500", "250 mg and 500 mg", "and 500 mg fda", "mg fda 2016", "fda 2016 bayer", "bayer inc 2020 .

              cipro", "inc 2020 .

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              very", "2005 .

              very high concentrations", ".

              very high concentrations of", "

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deblasi et al", "deblasi et al 2020" ] }, { "record_id": "GLY_000594_1_2068", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9755088", "r hsa", "hsa 9755088", "r hsa 9755088" ] }, { "record_id": "GLY_000594_1_2068", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "ribavirin adme", "is a", "a synthetic", "synthetic nucleoside", "nucleoside analog", "analog structurally", "structurally related", "related to", "to guanine.", "guanine. it", "it is", "is given", "given orally", "orally as", "as part", "part of", "of the", "the treatment", "treatment of", "of hcv", "hcv infection", "and by", "by inhalation", "inhalation for", "for the", "of rsv", "rsv infection.", "infection. according", "according to", "to the", "the who", "ribavirin can", "can also", "also be", "be used", "used for", "of viral", "viral hemorrhagic", "hemorrhagic fevers", "who 2015", "2015 .
              rbv", ".
              rbv is", "is administered", "administered orally", "orally in", "in doses", "doses of", "of 400", "400 to", "to 600", "600 mg.", "mg. it", "is highly", "highly soluble", "soluble in", "in water", "water and", "and a", "a typical", "typical dose", "dose is", "is dissolved", "dissolved completely", "completely over", "over a", "a wide", "wide range", "range of", "of acidities.", "acidities. rbv", "rbv is", "is rapidly", "rapidly absorbed", "absorbed into", "into the", "the circulation.", "circulation. after", "after the", "the oral", "oral administration", "administration of", "of 600", "600 mg", "mg radiolabeled", "radiolabeled ribavirin", "approximately 61%", "61% of", "the drug", "drug was", "was detected", "detected in", "in the", "the urine", "urine and", "and 12%", "12% was", "the feces.", "feces. 17%", "17% of", "of an", "an administered", "administered dose", "dose was", "was in", "in unchanged", "unchanged form.", "form. rbv", "rbv accumulates", "accumulates in", "in human", "human erythrocytes", "erythrocytes and", "and remains", "remains in", "the body", "body for", "for weeks", "with a", "a halflife", "halflife of", "of >100", ">100 hours", "goodarzi et", "et al", "2016 .", ". a", "a consequence", "consequence of", "the accumulation", "accumulation in", "in erythrocytes", "erythrocytes is", "is the", "the well", "well known", "known side", "side effect", "effect of", "of hemolytic", "hemolytic anemia", "which is", "is reversible", "reversible by", "by cessation", "cessation of", "of administration", "fda label", "label rebetol", "2013 .
              ribavirin", ".
              ribavirin is", "a prodrug.", "prodrug. it", "is metabolized", "metabolized through", "through two", "two different", "different paths:", "paths: phosphorylation", "yielding the", "the active", "active triphosphate", "rbv tp", "and degradation", "degradation via", "via de", "de ribosylation", "ribosylation and", "and hydrolysis", "hydrolysis of", "the amide", "amide group.", "group. the", "the gi", "gi tract", "and not", "not the", "the liver", "appears to", "to be", "be the", "the major", "major site", "site of", "of first", "first pass", "pass elimination", "dixit and", "and perelson", "2006 .", "ribavirin rbv", "is a synthetic", "a synthetic nucleoside", "synthetic nucleoside analog", "nucleoside analog structurally", "analog structurally related", "structurally related to", "related to guanine.", "to guanine. it", "guanine. it is", "it is given", "is given orally", "given orally as", "orally as part", "as part of", "part of the", "of the treatment", "the treatment of", "treatment of hcv", "of hcv infection", "infection and", "and by inhalation", "by inhalation for", "inhalation for the", "for the treatment", "treatment of rsv", "of rsv infection.", "rsv infection. according", "infection. according to", "according to the", "to the who", "who ribavirin", "ribavirin can also", "can also be", "also be used", "be used for", "used for the", "treatment of viral", "of viral hemorrhagic", "viral hemorrhagic fevers", "fevers who", "who 2015 .
              rbv", "2015 .
              rbv is", ".
              rbv is administered", "is administered orally", "administered orally in", "orally in doses", "in doses of", "doses of 400", "of 400 to", "400 to 600", "to 600 mg.", "600 mg. it", "mg. it is", "it is highly", "is highly soluble", "highly soluble in", "soluble in water", "in water and", "water and a", "and a typical", "a typical dose", "typical dose is", "dose is dissolved", "is dissolved completely", "dissolved completely over", "completely over a", "over a wide", "a wide range", "wide range of", "range of acidities.", "of acidities. rbv", "acidities. rbv is", "rbv is rapidly", "is rapidly absorbed", "rapidly absorbed into", "absorbed into the", "into the circulation.", "the circulation. after", "circulation. after the", "after the oral", "the oral administration", "oral administration of", "administration of 600", "of 600 mg", "600 mg radiolabeled", "mg radiolabeled ribavirin", "ribavirin approximately", "approximately 61% of", "61% of the", "of the drug", "the drug was", "drug was detected", "was detected in", "detected in the", "in the urine", "the urine and", "urine and 12%", "and 12% was", "12% was detected", "in the feces.", "the feces. 17%", "feces. 17% of", "17% of an", "of an administered", "an administered dose", "administered dose was", "dose was in", "was in unchanged", "in unchanged form.", "unchanged form. rbv", "form. rbv accumulates", "rbv accumulates in", "accumulates in human", "in human erythrocytes", "human erythrocytes and", "erythrocytes and remains", "and remains in", "remains in the", "in the body", "the body for", "body for weeks", "weeks with", "with a halflife", "a halflife of", "halflife of >100", "of >100 hours", "hours goodarzi", "goodarzi et al", "al 2016", "2016 . a", ". a consequence", "a consequence of", "consequence of the", "of the accumulation", "the accumulation in", "accumulation in erythrocytes", "in erythrocytes is", "erythrocytes is the", "is the well", "the well known", "well known side", "known side effect", "side effect of", "effect of hemolytic", "of hemolytic anemia", "anemia which", "which is reversible", "is reversible by", "reversible by cessation", "by cessation of", "cessation of administration", "administration fda", "fda label rebetol", "rebetol 2013", "2013 .
              ribavirin is", ".
              ribavirin is a", "is a prodrug.", "a prodrug. it", "prodrug. it is", "it is metabolized", "is metabolized through", "metabolized through two", "through two different", "two different paths:", "different paths: phosphorylation", "phosphorylation yielding", "yielding the active", "the active triphosphate", "triphosphate rbv", "and degradation via", "degradation via de", "via de ribosylation", "de ribosylation and", "ribosylation and hydrolysis", "and hydrolysis of", "hydrolysis of the", "of the amide", "the amide group.", "amide group. the", "group. the gi", "the gi tract", "tract and", "and not the", "not the liver", "liver appears", "appears to be", "to be the", "be the major", "the major site", "major site of", "site of first", "of first pass", "first pass elimination", "elimination dixit", "dixit and perelson", "perelson 2006", "rbv is a", "is a synthetic nucleoside", "a synthetic nucleoside analog", "synthetic nucleoside analog structurally", "nucleoside analog structurally related", "analog structurally related to", "structurally related to guanine.", "related to guanine. it", "to guanine. it is", "guanine. it is given", "it is given orally", "is given orally as", "given orally as part", "orally as part of", "as part of the", "part of the treatment", "of the treatment of", "the treatment of hcv", "treatment of hcv infection", "hcv infection and", "infection and by", "and by inhalation for", "by inhalation for the", "inhalation for the treatment", "for the treatment of", "the treatment of rsv", "treatment of rsv infection.", "of rsv infection. according", "rsv infection. according to", "infection. according to the", "according to the who", "the who ribavirin", "who ribavirin can", "ribavirin can also be", "can also be used", "also be used for", "be used for the", "used for the treatment", "the treatment of viral", "treatment of viral hemorrhagic", "of viral hemorrhagic fevers", "hemorrhagic fevers who", "fevers who 2015", "who 2015 .
              rbv is", "2015 .
              rbv is administered", ".
              rbv is administered orally", "is administered orally in", "administered orally in doses", "orally in doses of", "in doses of 400", "doses of 400 to", "of 400 to 600", "400 to 600 mg.", "to 600 mg. it", "600 mg. it is", "mg. it is highly", "it is highly soluble", "is highly soluble in", "highly soluble in water", "soluble in water and", "in water and a", "water and a typical", "and a typical dose", "a typical dose is", "typical dose is dissolved", "dose is dissolved completely", "is dissolved completely over", "dissolved completely over a", "completely over a wide", "over a wide range", "a wide range of", "wide range of acidities.", "range of acidities. rbv", "of acidities. rbv is", "acidities. rbv is rapidly", "rbv is rapidly absorbed", "is rapidly absorbed into", "rapidly absorbed into the", "absorbed into the circulation.", "into the circulation. after", "the circulation. after the", "circulation. after the oral", "after the oral administration", "the oral administration of", "oral administration of 600", "administration of 600 mg", "of 600 mg radiolabeled", "600 mg radiolabeled ribavirin", "radiolabeled ribavirin approximately", "ribavirin approximately 61%", "approximately 61% of the", "61% of the drug", "of the drug was", "the drug was detected", "drug was detected in", "was detected in the", "detected in the urine", "in the urine and", "the urine and 12%", "urine and 12% was", "and 12% was detected", "12% was detected in", "detected in the feces.", "in the feces. 17%", "the feces. 17% of", "feces. 17% of an", "17% of an administered", "of an administered dose", "an administered dose was", "administered dose was in", "dose was in unchanged", "was in unchanged form.", "in unchanged form. rbv", "unchanged form. rbv accumulates", "form. rbv accumulates in", "rbv accumulates in human", "accumulates in human erythrocytes", "in human erythrocytes and", "human erythrocytes and remains", "erythrocytes and remains in", "and remains in the", "remains in the body", "in the body for", "the body for weeks", "for weeks with", "weeks with a", "with a halflife of", "a halflife of >100", "halflife of >100 hours", ">100 hours goodarzi", "hours goodarzi et", "et al 2016", "al 2016 .", "2016 . a consequence", ". a consequence of", "a consequence of the", "consequence of the accumulation", "of the accumulation in", "the accumulation in erythrocytes", "accumulation in erythrocytes is", "in erythrocytes is the", "erythrocytes is the well", "is the well known", "the well known side", "well known side effect", "known side effect of", "side effect of hemolytic", "effect of hemolytic anemia", "hemolytic anemia which", "anemia which is", "which is reversible by", "is reversible by cessation", "reversible by cessation of", "by cessation of administration", "of administration fda", "administration fda label", "label rebetol 2013", "rebetol 2013 .
              ribavirin", "2013 .
              ribavirin is a", ".
              ribavirin is a prodrug.", "is a prodrug. it", "a prodrug. it is", "prodrug. it is metabolized", "it is metabolized through", "is metabolized through two", "metabolized through two different", "through two different paths:", "two different paths: phosphorylation", "paths: phosphorylation yielding", "phosphorylation yielding the", "yielding the active triphosphate", "active triphosphate rbv", "triphosphate rbv tp", "tp and", "and degradation via de", "degradation via de ribosylation", "via de ribosylation and", "de ribosylation and hydrolysis", "ribosylation and hydrolysis of", "and hydrolysis of the", "hydrolysis of the amide", "of the amide group.", "the amide group. the", "amide group. the gi", "group. the gi tract", "gi tract and", "tract and not", "and not the liver", "the liver appears", "liver appears to", "appears to be the", "to be the major", "be the major site", "the major site of", "major site of first", "site of first pass", "of first pass elimination", "pass elimination dixit", "elimination dixit and", "and perelson 2006", "perelson 2006 .", "ribavirin rbv is", "rbv is a synthetic", "is a synthetic nucleoside analog", "a synthetic nucleoside analog structurally", "synthetic nucleoside analog structurally related", "nucleoside analog structurally related to", "analog structurally related to guanine.", "structurally related to guanine. it", "related to guanine. it is", "to guanine. it is given", "guanine. it is given orally", "it is given orally as", "is given orally as part", "given orally as part of", "orally as part of the", "as part of the treatment", "part of the treatment of", "of the treatment of hcv", "the treatment of hcv infection", "of hcv infection and", "hcv infection and by", "infection and by inhalation", "and by inhalation for the", "by inhalation for the treatment", "inhalation for the treatment of", "for the treatment of rsv", "the treatment of rsv infection.", "treatment of rsv infection. according", "of rsv infection. according to", "rsv infection. according to the", "infection. according to the who", "to the who ribavirin", "the who ribavirin can", "who ribavirin can also", "ribavirin can also be used", "can also be used for", "also be used for the", "be used for the treatment", "used for the treatment of", "for the treatment of viral", "the treatment of viral hemorrhagic", "treatment of viral hemorrhagic fevers", "viral hemorrhagic fevers who", "hemorrhagic fevers who 2015", "fevers who 2015 .
              rbv", "who 2015 .
              rbv is administered", "2015 .
              rbv is administered orally", ".
              rbv is administered orally in", "is administered orally in doses", "administered orally in doses of", "orally in doses of 400", "in doses of 400 to", "doses of 400 to 600", "of 400 to 600 mg.", "400 to 600 mg. it", "to 600 mg. it is", "600 mg. it is highly", "mg. it is highly soluble", "it is highly soluble in", "is highly soluble in water", "highly soluble in water and", "soluble in water and a", "in water and a typical", "water and a typical dose", "and a typical dose is", "a typical dose is dissolved", "typical dose is dissolved completely", "dose is dissolved completely over", "is dissolved completely over a", "dissolved completely over a wide", "completely over a wide range", "over a wide range of", "a wide range of acidities.", "wide range of acidities. rbv", "range of acidities. rbv is", "of acidities. rbv is rapidly", "acidities. rbv is rapidly absorbed", "rbv is rapidly absorbed into", "is rapidly absorbed into the", "rapidly absorbed into the circulation.", "absorbed into the circulation. after", "into the circulation. after the", "the circulation. after the oral", "circulation. after the oral administration", "after the oral administration of", "the oral administration of 600", "oral administration of 600 mg", "administration of 600 mg radiolabeled", "of 600 mg radiolabeled ribavirin", "mg radiolabeled ribavirin approximately", "radiolabeled ribavirin approximately 61%", "ribavirin approximately 61% of", "approximately 61% of the drug", "61% of the drug was", "of the drug was detected", "the drug was detected in", "drug was detected in the", "was detected in the urine", "detected in the urine and", "in the urine and 12%", "the urine and 12% was", "urine and 12% was detected", "and 12% was detected in", "12% was detected in the", "was detected in the feces.", "detected in the feces. 17%", "in the feces. 17% of", "the feces. 17% of an", "feces. 17% of an administered", "17% of an administered dose", "of an administered dose was", "an administered dose was in", "administered dose was in unchanged", "dose was in unchanged form.", "was in unchanged form. rbv", "in unchanged form. rbv accumulates", "unchanged form. rbv accumulates in", "form. rbv accumulates in human", "rbv accumulates in human erythrocytes", "accumulates in human erythrocytes and", "in human erythrocytes and remains", "human erythrocytes and remains in", "erythrocytes and remains in the", "and remains in the body", "remains in the body for", "in the body for weeks", "body for weeks with", "for weeks with a", "weeks with a halflife", "with a halflife of >100", "a halflife of >100 hours", "of >100 hours goodarzi", ">100 hours goodarzi et", "hours goodarzi et al", "goodarzi et al 2016", "et al 2016 .", "al 2016 . a", "2016 . a consequence of", ". a consequence of the", "a consequence of the accumulation", "consequence of the accumulation in", "of the accumulation in erythrocytes", "the accumulation in erythrocytes is", "accumulation in erythrocytes is the", "in erythrocytes is the well", "erythrocytes is the well known", "is the well known side", "the well known side effect", "well known side effect of", "known side effect of hemolytic", "side effect of hemolytic anemia", "of hemolytic anemia which", "hemolytic anemia which is", "anemia which is reversible", "which is reversible by cessation", "is reversible by cessation of", "reversible by cessation of administration", "cessation of administration fda", "of administration fda label", "administration fda label rebetol", "fda label rebetol 2013", "label rebetol 2013 .
              ribavirin", "rebetol 2013 .
              ribavirin is", "2013 .
              ribavirin is a prodrug.", ".
              ribavirin is a prodrug. it", "is a prodrug. it is", "a prodrug. it is metabolized", "prodrug. it is metabolized through", "it is metabolized through two", "is metabolized through two different", "metabolized through two different paths:", "through two different paths: phosphorylation", "different paths: phosphorylation yielding", "paths: phosphorylation yielding the", "phosphorylation yielding the active", "the active triphosphate rbv", "active triphosphate rbv tp", "rbv tp and", "tp and degradation", "and degradation via de ribosylation", "degradation via de ribosylation and", "via de ribosylation and hydrolysis", "de ribosylation and hydrolysis of", "ribosylation and hydrolysis of the", "and hydrolysis of the amide", "hydrolysis of the amide group.", "of the amide group. the", "the amide group. the gi", "amide group. the gi tract", "the gi tract and", "gi tract and not", "tract and not the", "not the liver appears", "the liver appears to", "liver appears to be", "appears to be the major", "to be the major site", "be the major site of", "the major site of first", "major site of first pass", "site of first pass elimination", "first pass elimination dixit", "pass elimination dixit and", "elimination dixit and perelson", "dixit and perelson 2006", "and perelson 2006 ." ] }, { "record_id": "GLY_000594_1_2069", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9757110", "r hsa", "hsa 9757110", "r hsa 9757110" ] }, { "record_id": "GLY_000594_1_2069", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "prednisone adme", "is a", "a prodrug", "prodrug of", "of prednisolone", "and is", "is rapidly", "rapidly absorbed.", "absorbed. to", "to achieve", "achieve high", "high uptake", "uptake of", "of the", "the near", "near water", "water insoluble", "insoluble molecule", "molecule the", "the highest", "highest dose", "dose 50", "50 mg", "mg has", "has to", "to be", "be dissolved", "dissolved in", "in 250", "250 ml", "ml water.", "water. its", "its conversion", "conversion to", "to the", "the highly", "highly active", "active prednisolone", "in liver", "liver cells", "cells is", "is reversible", "reversible but", "but represents", "represents the", "the favored", "favored reaction", "reaction direction", "1979 .
              prednisone", ".
              prednisone and", "and prednisolone", "prednisolone are", "are considered", "considered to", "be fully", "fully therapeutically", "therapeutically equivalent.", "equivalent. the", "the theoretical", "theoretical advantage", "advantage of", "of avoiding", "avoiding high", "high gi", "gi concentrations", "concentrations of", "of prednisone", "prednisone by", "by administering", "administering prednisolone", "prednisolone directly", "directly has", "has never", "never been", "been shown", "shown to", "be clinically", "clinically relevant", "vogt et", "et al", "2007 .
              only", ".
              only 2\u20135%", "2\u20135% of", "of a", "a given", "given dose", "dose of", "prednisone is", "is excreted", "excreted unchanged", "unchanged in", "in urine.", "urine. after", "after hydrogenation", "hydrogenation to", "to prednisolone", "prednisolone at", "at least", "least 20", "20 metabolites", "metabolites and", "and their", "their conjugates", "conjugates are", "are formed", "formed and", "and excreted.", "excreted. the", "the main", "main metabolites", "metabolites both", "both after", "after systemic", "systemic and", "and topical", "topical use", "use are", "are 20alpha", "and 20beta", "20beta dihydro", "dihydro prednisone", "as well", "well as", "as 20alpha", "dihydro prednisolone", "20ah predn", "20bh predn", "20ah predl", "20bh predl", "in addition", "addition to", "the 6beta", "6beta hydroxy", "hydroxy compounds", "compounds 6b", "6b oh", "oh predn", "predn and", "and 6b", "oh predl", "matabosch et", "mazzarino et", "2019 .", ". hydrogenation", "hydrogenation of", "of predn", "and dehydrogenation", "dehydrogenation of", "of predl", "predl are", "are complementary", "complementary reactions", "reactions that", "that are", "are dominant", "dominant in", "in different", "different cell", "cell types.", "types. while", "while liver", "liver and", "and fat", "fat cells", "cells convert", "convert predn", "predn to", "to predl", "colon and", "and kidney", "kidney cells", "cells partly", "partly convert", "convert predl", "predl back", "back to", "to predn", "jamieson et", "ricketts et", "diederichs et", "2002 .", ". we", "we have", "have depicted", "depicted this", "this equilibrium", "equilibrium by", "by showing", "showing example", "example reactions", "reactions in", "in hepatocytes", "hepatocytes and", "cells in", "in the", "the diagram.", "prednisone predn", "predn is", "is a prodrug", "a prodrug of", "prodrug of prednisolone", "prednisolone predl", "and is rapidly", "is rapidly absorbed.", "rapidly absorbed. to", "absorbed. to achieve", "to achieve high", "achieve high uptake", "high uptake of", "uptake of the", "of the near", "the near water", "near water insoluble", "water insoluble molecule", "insoluble molecule the", "molecule the highest", "the highest dose", "highest dose 50", "dose 50 mg", "50 mg has", "mg has to", "has to be", "to be dissolved", "be dissolved in", "dissolved in 250", "in 250 ml", "250 ml water.", "ml water. its", "water. its conversion", "its conversion to", "conversion to the", "to the highly", "the highly active", "highly active prednisolone", "predl in", "in liver cells", "liver cells is", "cells is reversible", "is reversible but", "reversible but represents", "but represents the", "represents the favored", "the favored reaction", "favored reaction direction", "direction pickup", "pickup 1979", "1979 .
              prednisone and", ".
              prednisone and prednisolone", "and prednisolone are", "prednisolone are considered", "are considered to", "considered to be", "to be fully", "be fully therapeutically", "fully therapeutically equivalent.", "therapeutically equivalent. the", "equivalent. the theoretical", "the theoretical advantage", "theoretical advantage of", "advantage of avoiding", "of avoiding high", "avoiding high gi", "high gi concentrations", "gi concentrations of", "concentrations of prednisone", "of prednisone by", "prednisone by administering", "by administering prednisolone", "administering prednisolone directly", "prednisolone directly has", "directly has never", "has never been", "never been shown", "been shown to", "shown to be", "to be clinically", "be clinically relevant", "relevant vogt", "vogt et al", "al 2007", "2007 .
              only 2\u20135%", ".
              only 2\u20135% of", "2\u20135% of a", "of a given", "a given dose", "given dose of", "dose of prednisone", "of prednisone is", "prednisone is excreted", "is excreted unchanged", "excreted unchanged in", "unchanged in urine.", "in urine. after", "urine. after hydrogenation", "after hydrogenation to", "hydrogenation to prednisolone", "to prednisolone at", "prednisolone at least", "at least 20", "least 20 metabolites", "20 metabolites and", "metabolites and their", "and their conjugates", "their conjugates are", "conjugates are formed", "are formed and", "formed and excreted.", "and excreted. the", "excreted. the main", "the main metabolites", "main metabolites both", "metabolites both after", "both after systemic", "after systemic and", "systemic and topical", "and topical use", "topical use are", "use are 20alpha", "20alpha and", "and 20beta dihydro", "20beta dihydro prednisone", "prednisone as", "as well as", "well as 20alpha", "20beta dihydro prednisolone", "prednisolone 20ah", "predn 20bh", "predn 20ah", "predl 20bh", "in addition to", "addition to the", "to the 6beta", "the 6beta hydroxy", "6beta hydroxy compounds", "hydroxy compounds 6b", "compounds 6b oh", "6b oh predn", "oh predn and", "predn and 6b", "and 6b oh", "6b oh predl", "predl matabosch", "matabosch et al", "al 2015", "2015 mazzarino", "mazzarino et al", "al 2019", "2019 . hydrogenation", ". hydrogenation of", "hydrogenation of predn", "of predn and", "predn and dehydrogenation", "and dehydrogenation of", "dehydrogenation of predl", "of predl are", "predl are complementary", "are complementary reactions", "complementary reactions that", "reactions that are", "that are dominant", "are dominant in", "dominant in different", "in different cell", "different cell types.", "cell types. while", "types. while liver", "while liver and", "liver and fat", "and fat cells", "fat cells convert", "cells convert predn", "convert predn to", "predn to predl", "predl colon", "colon and kidney", "and kidney cells", "kidney cells partly", "cells partly convert", "partly convert predl", "convert predl back", "predl back to", "back to predn", "predn jamieson", "jamieson et al", "al 1995", "1995 ricketts", "ricketts et al", "al 1998", "1998 diederichs", "diederichs et al", "al 2002", "2002 . we", ". we have", "we have depicted", "have depicted this", "depicted this equilibrium", "this equilibrium by", "equilibrium by showing", "by showing example", "showing example reactions", "example reactions in", "reactions in hepatocytes", "in hepatocytes and", "hepatocytes and kidney", "kidney cells in", "cells in the", "in the diagram.", "predn is a", "is a prodrug of", "a prodrug of prednisolone", "of prednisolone predl", "predl and", "and is rapidly absorbed.", "is rapidly absorbed. to", "rapidly absorbed. to achieve", "absorbed. to achieve high", "to achieve high uptake", "achieve high uptake of", "high uptake of the", "uptake of the near", "of the near water", "the near water insoluble", "near water insoluble molecule", "water insoluble molecule the", "insoluble molecule the highest", "molecule the highest dose", "the highest dose 50", "highest dose 50 mg", "dose 50 mg has", "50 mg has to", "mg has to be", "has to be dissolved", "to be dissolved in", "be dissolved in 250", "dissolved in 250 ml", "in 250 ml water.", "250 ml water. its", "ml water. its conversion", "water. its conversion to", "its conversion to the", "conversion to the highly", "to the highly active", "the highly active prednisolone", "active prednisolone predl", "predl in liver", "in liver cells is", "liver cells is reversible", "cells is reversible but", "is reversible but represents", "reversible but represents the", "but represents the favored", "represents the favored reaction", "the favored reaction direction", "reaction direction pickup", "pickup 1979 .
              prednisone", "1979 .
              prednisone and prednisolone", ".
              prednisone and prednisolone are", "and prednisolone are considered", "prednisolone are considered to", "are considered to be", "considered to be fully", "to be fully therapeutically", "be fully therapeutically equivalent.", "fully therapeutically equivalent. the", "therapeutically equivalent. the theoretical", "equivalent. the theoretical advantage", "the theoretical advantage of", "theoretical advantage of avoiding", "advantage of avoiding high", "of avoiding high gi", "avoiding high gi concentrations", "high gi concentrations of", "gi concentrations of prednisone", "concentrations of prednisone by", "of prednisone by administering", "prednisone by administering prednisolone", "by administering prednisolone directly", "administering prednisolone directly has", "prednisolone directly has never", "directly has never been", "has never been shown", "never been shown to", "been shown to be", "shown to be clinically", "to be clinically relevant", "clinically relevant vogt", "relevant vogt et", "et al 2007", "al 2007 .
              only", "2007 .
              only 2\u20135% of", ".
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              prednisone and", "1979 .
              prednisone and prednisolone are", ".
              prednisone and prednisolone are considered", "and prednisolone are considered to", "prednisolone are considered to be", "are considered to be fully", "considered to be fully therapeutically", "to be fully therapeutically equivalent.", "be fully therapeutically equivalent. the", "fully therapeutically equivalent. the theoretical", "therapeutically equivalent. the theoretical advantage", "equivalent. the theoretical advantage of", "the theoretical advantage of avoiding", "theoretical advantage of avoiding high", "advantage of avoiding high gi", "of avoiding high gi concentrations", "avoiding high gi concentrations of", "high gi concentrations of prednisone", "gi concentrations of prednisone by", "concentrations of prednisone by administering", "of prednisone by administering prednisolone", "prednisone by administering prednisolone directly", "by administering prednisolone directly has", "administering prednisolone directly has never", "prednisolone directly has never been", "directly has never been shown", "has never been shown to", "never been shown to be", "been shown to be clinically", "shown to be clinically relevant", "be clinically relevant vogt", "clinically relevant vogt et", "relevant vogt et al", "vogt et al 2007", "et al 2007 .
              only", "al 2007 .
              only 2\u20135%", "2007 .
              only 2\u20135% of a", ".
              only 2\u20135% of a given", "2\u20135% of a given dose", "of a given dose of", "a given dose of prednisone", "given dose of prednisone is", "dose of prednisone is excreted", "of prednisone is excreted unchanged", "prednisone is excreted unchanged in", "is excreted unchanged in urine.", "excreted unchanged in urine. after", "unchanged in urine. after hydrogenation", "in urine. after hydrogenation to", "urine. after hydrogenation to prednisolone", "after hydrogenation to prednisolone at", "hydrogenation to prednisolone at least", "to prednisolone at least 20", "prednisolone at least 20 metabolites", "at least 20 metabolites and", "least 20 metabolites and their", "20 metabolites and their conjugates", "metabolites and their conjugates are", "and their conjugates are formed", "their conjugates are formed and", "conjugates are formed and excreted.", "are formed and excreted. the", "formed and excreted. the main", "and excreted. the main metabolites", "excreted. the main metabolites both", "the main metabolites both after", "main metabolites both after systemic", "metabolites both after systemic and", "both after systemic and topical", "after systemic and topical use", "systemic and topical use are", "and topical use are 20alpha", "use are 20alpha and", "are 20alpha and 20beta", "20alpha and 20beta dihydro", "20beta dihydro prednisone as", "dihydro prednisone as well", "prednisone as well as", "well as 20alpha and", "as 20alpha and 20beta", "20beta dihydro prednisolone 20ah", "dihydro prednisolone 20ah predn", "20ah predn 20bh predn", "20bh predn 20ah predl", "20ah predl 20bh predl", "20bh predl in", "predl in addition", "in addition to the 6beta", "addition to the 6beta hydroxy", "to the 6beta hydroxy compounds", "the 6beta hydroxy compounds 6b", "6beta hydroxy compounds 6b oh", "hydroxy compounds 6b oh predn", "compounds 6b oh predn and", "6b oh predn and 6b", "oh predn and 6b oh", "predn and 6b oh predl", "6b oh predl matabosch", "oh predl matabosch 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              in the lateral plate", "streak.
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"1997 . hedgehog proteins shh", ". hedgehog proteins shh and", "hedgehog proteins shh and ihh", "proteins shh and ihh activate", "shh and ihh activate expression", "and ihh activate expression of", "ihh activate expression of foxf1", "expression of foxf1 a", "of foxf1 a marker", "foxf1 a marker of", "a marker of the lateral", "marker of the lateral plate", "of the lateral plate mesoderm", "the lateral plate mesoderm following", "lateral plate mesoderm following its", "plate mesoderm following its induction", "following its induction inferred", "its induction inferred from", "induction inferred from mouse", "from mouse homologs in rojas", "mouse homologs in rojas et", "homologs in rojas et al.", "in rojas et al. 2005", "et al. 2005 astorga", "al. 2005 astorga and", "2005 astorga and carlsson", "astorga and carlsson 2007 .", "and carlsson 2007 . bmp4", "carlsson 2007 . bmp4 may", "2007 . bmp4 may also", ". bmp4 may also activate", "bmp4 may also activate foxh1", "may also activate foxh1 in", "also activate foxh1 in the", "activate foxh1 in the primitive", "foxh1 in the primitive streak", "in the primitive streak and", "the primitive streak and lateral", "primitive streak and lateral plate", "streak and lateral plate mesoderm", "lateral plate mesoderm inferred", "plate mesoderm inferred from", "mesoderm inferred from xenopus", "inferred from xenopus homologs in", "from xenopus homologs in tseng", "xenopus homologs in tseng et", "homologs in tseng et al.", "in tseng et al. 2004", "tseng et al. 2004 .", "al. 2004 . foxf1", "2004 . foxf1 activates", ". foxf1 activates expression", "foxf1 activates expression of bmp4", "activates expression of bmp4 and", "expression of bmp4 and bmp4", "of bmp4 and bmp4 together", "bmp4 and bmp4 together with", "and bmp4 together with foxf1", "bmp4 together with foxf1 activate", "together with foxf1 activate gata4", "foxf1 activate gata4 inferred", "activate gata4 inferred from", "gata4 inferred from mouse", "rojas et al. 2005 ..", "et al. 2005 .. bmp4", "al. 2005 .. bmp4 maintains", "2005 .. bmp4 maintains the", ".. bmp4 maintains the expression", "bmp4 maintains the expression of", "maintains the expression of foxf1.", "the expression of foxf1. gata4", "expression of foxf1. gata4 maintains", "of foxf1. gata4 maintains its", "foxf1. gata4 maintains its own", "gata4 maintains its own expression", "maintains its own expression and", "its own expression and the", "own expression and the expression", "expression and the expression of", "and the expression of bmp4.", "the expression of bmp4. foxf1", "expression of bmp4. foxf1 and", "of bmp4. foxf1 and gata4", "bmp4. foxf1 and gata4 then", "foxf1 and gata4 then activate", "and gata4 then activate expression", "gata4 then activate expression of", "then activate expression of downstream", "activate expression of downstream genes", "expression of downstream genes that", "of downstream genes that further", "downstream genes that further differentiate", "genes that further differentiate the", "that further differentiate the lateral", "further differentiate the lateral plate", "differentiate the lateral plate mesoderm.", "the lateral plate mesoderm. in", "lateral plate mesoderm. in zebrafish", "mesoderm. in zebrafish the", "in zebrafish the combined", "zebrafish the combined activity", "the combined activity of eomesodermin", "activity of eomesodermin foxh1", "eomesodermin foxh1 and", "and mixl1 together with", "mixl1 together with smad", "together with smad proteins induces", "with smad proteins induces lateral", "smad proteins induces lateral plate", "proteins induces lateral plate mesoderm", "induces lateral plate mesoderm and", "lateral plate mesoderm and this", "plate mesoderm and this mechanism", "mesoderm and this mechanism may", "and this mechanism may be", "this mechanism may be shared", "mechanism may be shared across", "may be shared across chordates", "shared across chordates prummel", "across chordates prummel et", "chordates prummel et al.", "prummel et al. 2019 ." ] }, { "record_id": "GLY_000594_1_2075", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9768777", "r hsa", "hsa 9768777", "r hsa 9768777" ] }, { "record_id": "GLY_000594_1_2075", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of npas4", "npas4 gene", "gene transcription", "regulation of npas4", "of npas4 gene", "npas4 gene transcription", "regulation of npas4 gene", "of npas4 gene transcription", "regulation of npas4 gene transcription", "transcription of", "of the", "the npas4", "gene is", "is positively", "positively regulated", "regulated by", "by neuronal", "neuronal stimulation", "stimulation related", "related increase", "increase in", "in intracellular", "intracellular calcium", "calcium levels", "lin et", "et al.", "al. 2008", "zhang et", "al. 2009", "mellstr\u00f6m et", "al. 2014", "lobos et", "al. 2021", "2021 .

              in", ".

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              srf", "serum response", "response factor", "stimulates npas4", "transcription upon", "kuzniewska et", "al. 2016", "l\u00f6sing et", "f\u00f6rstner and", "and kn\u00f6ll", "kn\u00f6ll 2019", "2019 .", ". npas4", "transcription is", "by pi3k/akt", "pi3k/akt signaling", "ooe et", "speckmann et", "and only", "only partially", "partially dependent", "dependent on", "on erk", "bl\u00fcthgen et", "2017 .", "npas4 may", "may be", "be one", "one of", "the egr1", "egr1 target", "target genes", "han et", ". neuronal", "activity stimulation", "stimulation may", "may trigger", "trigger the", "the formation", "formation of", "of dna", "dna double", "double strand", "strand breaks", "the promoters", "promoters of", "of a", "a subset", "subset of", "of early", "early response", "response genes", "including fos", "and egr1", "which may", "may contribute", "to their", "their transcriptional", "transcriptional activation", "madabushi et", "al. 2015", "2015 .", "npas4 appears", "appears to", "be a", "a downstream", "downstream target", "target involved", "involved in", "in amyloid", "amyloid precursor", "precursor protein", "dependent regulation", "of inhibitory", "inhibitory synaptic", "synaptic transmission", "opsomer et", "al. 2020", "2020 .", ". tet1", "a methylcytosine", "methylcytosine dioxygenase", "dioxygenase that", "that catalyzes", "catalyzes oxidation", "oxidation of", "of 5", "5 methylcytosine", "to 5", "5 hydroxymethylcytosine", "and promotes", "promotes dna", "dna demethylation", "demethylation is", "is implicated", "implicated in", "in transcriptional", "activation of", "gene through", "through demethylation", "demethylation of", "of hypermethylated", "hypermethylated cpg", "cpg dinucleotides", "dinucleotides in", "gene promoter", "promoter region", "rudenko et", "al. 2013", "2013 .", ". transcriptional", "is associated", "associated with", "with the", "the appearance", "appearance of", "of h3k4me3", "h3k4me3 mark", "mark and", "and 5hmc", "5hmc mark", "mark at", "at the", "webb et", "transcription of the", "of the npas4", "the npas4 gene", "npas4 gene is", "gene is positively", "is positively regulated", "positively regulated by", "regulated by neuronal", "by neuronal stimulation", "neuronal stimulation related", "stimulation related increase", "related increase in", "increase in intracellular", "in intracellular calcium", "intracellular calcium levels", "levels lin", "lin et al.", "et al. 2008", "2008 zhang", "zhang et al.", "et al. 2009", "2009 mellstr\u00f6m", "mellstr\u00f6m et al.", "et al. 2014", "2014 lobos", "lobos et al.", "et al. 2021", "al. 2021 .

              in", "2021 .

              in the", ".

              in the absence", "the absence of", "absence of neuronal", "of neuronal activity", "neuronal activity induced", "activity induced calcium", "induced calcium influx", "influx kcnip3", "kcnip3 dream", "dream binds", "binds to the", "to the promoter", "the promoter of", "promoter of the", "npas4 gene and", "gene and represses", "and represses npas4", "represses npas4 transcription", "transcription mellstr\u00f6m", "al. 2014 .", "2014 . in", ". in non", "in non neuronal", "non neuronal cells", "cells rest", "rest protein represses", "protein represses transcription", "represses transcription of", "gene bersten", "bersten et al.", ". in neuronal", "in neuronal cells", "rest may have", "may have a", "have a dual", "a dual effect", "dual effect on", "effect on npas4", "on npas4 expression:", "npas4 expression: acting", "expression: acting as", "acting as a", "as a positive", "a positive regulator", "positive regulator of", "regulator of npas4", "of npas4 transcription", "npas4 transcription early", "transcription early upon", "early upon neuronal", "upon neuronal excitation", "neuronal excitation and", "excitation and as", "and as a", "as a negative", "a negative regulator", "negative regulator at", "regulator at later", "at later time", "later time points", "points allowing", "allowing npas4 to", "npas4 to return", "to return to", "return to basal", "to basal levels", "levels prestigio", "prestigio et al.", "al. 2021 .", "2021 . binding", ". binding of", "binding of agonist", "of agonist activated", "agonist activated glucocorticoid", "activated glucocorticoid receptor", "glucocorticoid receptor nr3c1", "nr3c1 also", "also known as", "known as gr", "gr to", "to evolutionarily conserved", "evolutionarily conserved glucocorticoid", "conserved glucocorticoid response", "glucocorticoid response elements", "elements gres", "gres upstream", "upstream of the", "gene transcription start", "transcription start site", "start site is", "site is responsible", "is responsible for", "responsible for stress", "for stress induced", "stress induced repression", "induced repression of", "repression of npas4", "transcription furukawa", "furukawa hibi et", "hibi et al.", "et al. 2012", "al. 2012 .", "2012 . chronic", ". chronic restraint", "chronic restraint stress", "restraint stress as", "stress as well", "as well as", "well as corticosterone", "as corticosterone injection", "corticosterone injection also", "injection also reduce", "also reduce npas4", "reduce npas4 gene", "npas4 gene expression", "gene expression in", "expression in the", "in the mouse", "the mouse hippocampus", "hippocampus yun", "yun et al.", "et al. 2010", "al. 2010 .", "2010 . though", ". though mechanisms", "though mechanisms remain", "mechanisms remain to", "remain to be", "to be delineated", "delineated hdac5", "hdac5 was reported", "was reported by", "reported by multiple", "by multiple studies", "multiple studies to", "studies to contribute", "to contribute to", "contribute to npas4", "to npas4 gene", "npas4 gene repression", "repression taniguchi", "taniguchi et al.", "et al. 2017", "2017 hashikawa", "hashikawa hobara et", "hobara et al.", "2021 lv", "lv et al.", "2021 rein", "rein et al.", "et al. 2022", "al. 2022 .", "2022 . in", ". in addition", "addition hdac3", "hdac3 was reported", "was reported as", "reported as the", "as the npas4", "npas4 gene repressor", "gene repressor during", "repressor during neurodegeneration", "neurodegeneration louis", "louis sam titus", "sam titus et", "titus et al.", "et al. 2019", "al. 2019 .

              srf", ".

              srf serum", "serum response factor", "factor stimulates", "stimulates npas4 gene", "gene transcription upon", "transcription upon neuronal", "excitation kuzniewska", "kuzniewska et al.", "et al. 2016", "2016 l\u00f6sing", "l\u00f6sing et al.", "2017 f\u00f6rstner", "f\u00f6rstner and kn\u00f6ll", "and kn\u00f6ll 2019", "kn\u00f6ll 2019 .", "2019 . npas4", ". npas4 gene", "gene transcription is", "transcription is positively", "regulated by pi3k/akt", "by pi3k/akt signaling", "signaling ooe", "ooe et al.", "2009 speckmann", "speckmann et al.", "and only partially", "only partially dependent", "partially dependent on", "dependent on erk", "erk mapk", "mapk signaling", "signaling bl\u00fcthgen", "bl\u00fcthgen et al.", "al. 2017 .", "2017 . npas4", ". npas4 may", "npas4 may be", "may be one", "be one of", "one of the", "of the egr1", "the egr1 target", "egr1 target genes", "genes han", "han et al.", "2014 . neuronal", ". neuronal activity", "neuronal activity stimulation", "activity stimulation may", "stimulation may trigger", "may trigger the", "trigger the formation", "the formation of", "formation of dna", "of dna double", "dna double strand", "double strand breaks", "breaks dsbs", "dsbs in", "in the promoters", "the promoters of", "promoters of a", "of a subset", "a subset of", "subset of early", "of early response", "early response genes", "genes including", "fos npas4", "npas4 and", "egr1 which", "which may contribute", "may contribute to", "contribute to their", "to their transcriptional", "their transcriptional activation", "activation madabushi", "madabushi et al.", "et al. 2015", "al. 2015 .", "2015 . npas4", ". npas4 appears", "npas4 appears to", "appears to be", "to be a", "be a downstream", "a downstream target", "downstream target involved", "target involved in", "involved in amyloid", "in amyloid precursor", "amyloid precursor protein", "protein app", "app dependent", "dependent regulation of", "regulation of inhibitory", "of inhibitory synaptic", "inhibitory synaptic transmission", "transmission opsomer", "opsomer et al.", "et al. 2020", "al. 2020 .", "2020 . tet1", "tet1 a", "a methylcytosine dioxygenase", "methylcytosine dioxygenase that", "dioxygenase that catalyzes", "that catalyzes oxidation", "catalyzes oxidation of", "oxidation of 5", "of 5 methylcytosine", "methylcytosine 5mc", "5mc to", "to 5 hydroxymethylcytosine", "hydroxymethylcytosine 5hmc", "5hmc and", "and promotes dna", "promotes dna demethylation", "dna demethylation is", "demethylation is implicated", "is implicated in", "implicated in transcriptional", "in transcriptional activation", "transcriptional activation of", "activation of npas4", "npas4 gene through", "gene through demethylation", "through demethylation of", "demethylation of hypermethylated", "of hypermethylated cpg", "hypermethylated cpg dinucleotides", "cpg dinucleotides in", "dinucleotides in the", "in the npas4", "npas4 gene promoter", "gene promoter region", "region rudenko", "rudenko et al.", "et al. 2013", "al. 2013 .", "2013 . transcriptional", ". transcriptional activation", "activation of the", "gene is associated", "is associated with", "associated with the", "with the appearance", "the appearance of", "appearance of h3k4me3", "of h3k4me3 mark", "h3k4me3 mark and", "mark and 5hmc", "and 5hmc mark", "5hmc mark at", "mark at the", "at the npas4", "promoter webb", "webb et al.", "transcription of the npas4", "of the npas4 gene", "the npas4 gene is", "npas4 gene is positively", "gene is positively regulated", "is positively regulated by", "positively regulated by neuronal", "regulated by neuronal stimulation", "by neuronal stimulation related", "neuronal stimulation related increase", "stimulation related increase in", "related increase in intracellular", "increase in intracellular calcium", "in intracellular calcium levels", "calcium levels lin", "levels lin et", "lin et al. 2008", "al. 2008 zhang", "2008 zhang et", "zhang et al. 2009", "al. 2009 mellstr\u00f6m", "2009 mellstr\u00f6m et", "mellstr\u00f6m et al. 2014", "al. 2014 lobos", "2014 lobos et", "lobos et al. 2021", "et al. 2021 .

              in", "al. 2021 .

              in the", "2021 .

              in the absence", ".

              in the absence of", "the absence of neuronal", "absence of neuronal activity", "of neuronal activity induced", "neuronal activity induced calcium", "activity induced calcium influx", "calcium influx kcnip3", "dream binds to", "binds to the promoter", "to the promoter of", "the promoter of the", "promoter of the npas4", "the npas4 gene and", "npas4 gene and represses", "gene and represses npas4", "and represses npas4 transcription", "npas4 transcription mellstr\u00f6m", "transcription mellstr\u00f6m et", "et al. 2014 .", "al. 2014 . in", "2014 . in non", ". in non neuronal", "in non neuronal cells", "neuronal cells rest", "cells rest protein", "rest protein represses transcription", "protein represses transcription of", "represses transcription of the", "npas4 gene bersten", "gene bersten et", "bersten et al. 2014", "2014 . in neuronal", ". in neuronal cells", "cells rest may", "rest may have a", "may have a dual", "have a dual effect", "a dual effect on", "dual effect on npas4", "effect on npas4 expression:", "on npas4 expression: acting", "npas4 expression: acting as", "expression: acting as a", "acting as a positive", "as a positive regulator", "a positive regulator of", "positive regulator of npas4", "regulator of npas4 transcription", "of npas4 transcription early", "npas4 transcription early upon", "transcription early upon neuronal", "early upon neuronal excitation", "upon neuronal excitation and", "neuronal excitation and as", "excitation and as a", "and as a negative", "as a negative regulator", "a negative regulator at", "negative regulator at later", "regulator at later time", "at later time points", "time points allowing", "points allowing npas4", "allowing npas4 to return", "npas4 to return to", "to return to basal", "return to basal levels", "basal levels prestigio", "levels prestigio et", "prestigio et al. 2021", "et al. 2021 .", "al. 2021 . binding", "2021 . binding of", ". binding of agonist", "binding of agonist activated", "of agonist activated glucocorticoid", "agonist activated glucocorticoid receptor", "activated glucocorticoid receptor nr3c1", "receptor nr3c1 also", "nr3c1 also known", "also known as gr", "as gr to", "gr to evolutionarily", "to evolutionarily conserved glucocorticoid", "evolutionarily conserved glucocorticoid response", "conserved glucocorticoid response elements", "response elements gres", "gres upstream of", "upstream of the npas4", "the npas4 gene transcription", "npas4 gene transcription start", "gene transcription start site", "transcription start site is", "start site is responsible", "site is responsible for", "is responsible for stress", "responsible for stress induced", "for stress induced repression", "stress induced repression of", "induced repression of npas4", "repression of npas4 gene", "gene transcription furukawa", "transcription furukawa hibi", "furukawa hibi et al.", "hibi et al. 2012", "et al. 2012 .", "al. 2012 . chronic", "2012 . chronic restraint", ". chronic restraint stress", "chronic restraint stress as", "restraint stress as well", "stress as well as", "as well as corticosterone", "well as corticosterone injection", "as corticosterone injection also", "corticosterone injection also reduce", "injection also reduce npas4", "also reduce npas4 gene", "reduce npas4 gene expression", "npas4 gene expression in", "gene expression in the", "expression in the mouse", "in the mouse hippocampus", "mouse hippocampus yun", "hippocampus yun et", "yun et al. 2010", "et al. 2010 .", "al. 2010 . though", "2010 . though mechanisms", ". though mechanisms remain", "though mechanisms remain to", "mechanisms remain to be", "remain to be delineated", "be delineated hdac5", "delineated hdac5 was", "hdac5 was reported by", "was reported by multiple", "reported by multiple studies", "by multiple studies to", "multiple studies to contribute", "studies to contribute to", "to contribute to npas4", "contribute to npas4 gene", "to npas4 gene repression", "gene repression taniguchi", "repression taniguchi et", "taniguchi et al. 2017", "al. 2017 hashikawa", "2017 hashikawa hobara", "hashikawa hobara et al.", "hobara et al. 2021", "al. 2021 lv", "2021 lv et", "lv et al. 2021", "al. 2021 rein", "2021 rein et", "rein et al. 2022", "et al. 2022 .", "al. 2022 . in", "2022 . in addition", "in addition hdac3", "addition hdac3 was", "hdac3 was reported as", "was reported as the", "reported as the npas4", "as the npas4 gene", "the npas4 gene repressor", "npas4 gene repressor during", "gene repressor during neurodegeneration", "during neurodegeneration louis", "neurodegeneration louis sam", "louis sam titus et", "sam titus et al.", "titus et al. 2019", "et al. 2019 .

              srf", "2019 .

              srf serum", ".

              srf serum response", "response factor stimulates", "factor stimulates npas4", "stimulates npas4 gene transcription", "npas4 gene transcription upon", "gene transcription upon neuronal", "transcription upon neuronal excitation", "neuronal excitation kuzniewska", "excitation kuzniewska et", "kuzniewska et al. 2016", "al. 2016 l\u00f6sing", "2016 l\u00f6sing et", "l\u00f6sing et al. 2017", "al. 2017 f\u00f6rstner", "2017 f\u00f6rstner and", "f\u00f6rstner and kn\u00f6ll 2019", "and kn\u00f6ll 2019 .", "kn\u00f6ll 2019 . npas4", "2019 . npas4 gene", ". npas4 gene transcription", "npas4 gene transcription is", "gene transcription is positively", "transcription is positively regulated", "positively regulated by pi3k/akt", "regulated by pi3k/akt signaling", "pi3k/akt signaling ooe", "signaling ooe et", "ooe et al. 2009", "al. 2009 speckmann", "2009 speckmann et", "speckmann et al. 2016", "2016 and", "and only partially dependent", "only partially dependent on", "partially dependent on erk", "on erk mapk", "signaling bl\u00fcthgen et", "bl\u00fcthgen et al. 2017", "et al. 2017 .", "al. 2017 . npas4", "2017 . npas4 may", ". npas4 may be", "npas4 may be one", "may be one of", "be one of the", "one of the egr1", "of the egr1 target", "the egr1 target genes", "target genes han", "genes han et", "han et al. 2014", "al. 2014 . neuronal", "2014 . neuronal activity", ". neuronal activity stimulation", "neuronal activity stimulation may", "activity stimulation may trigger", "stimulation may trigger the", "may trigger the formation", "trigger the formation of", "the formation of dna", "formation of dna double", "of dna double strand", "dna double strand breaks", "strand breaks dsbs", "dsbs in the", "in the promoters of", "the promoters of a", "promoters of a subset", "of a subset of", "a subset of early", "subset of early response", "of early response genes", "response genes including", "genes including fos", "including fos npas4", "npas4 and egr1", "and egr1 which", "egr1 which may", "which may contribute to", "may contribute to their", "contribute to their transcriptional", "to their transcriptional activation", "transcriptional activation madabushi", "activation madabushi et", "madabushi et al. 2015", "et al. 2015 .", "al. 2015 . npas4", "2015 . npas4 appears", ". npas4 appears to", "npas4 appears to be", "appears to be a", "to be a downstream", "be a downstream target", "a downstream target involved", "downstream target involved in", "target involved in amyloid", "involved in amyloid precursor", "in amyloid precursor protein", "precursor protein app", "app dependent regulation", "dependent regulation of inhibitory", "regulation of inhibitory synaptic", "of inhibitory synaptic transmission", "synaptic transmission opsomer", "transmission opsomer et", "opsomer et al. 2020", "et al. 2020 .", "al. 2020 . tet1", ". tet1 a", "tet1 a methylcytosine", "a methylcytosine dioxygenase that", "methylcytosine dioxygenase that catalyzes", "dioxygenase that catalyzes oxidation", "that catalyzes oxidation of", "catalyzes oxidation of 5", "oxidation of 5 methylcytosine", "5 methylcytosine 5mc", "5mc to 5", "5 hydroxymethylcytosine 5hmc", "5hmc and promotes", "and promotes dna demethylation", "promotes dna demethylation is", "dna demethylation is implicated", "demethylation is implicated in", "is implicated in transcriptional", "implicated in transcriptional activation", "in transcriptional activation of", "transcriptional activation of npas4", "activation of npas4 gene", "of npas4 gene through", "npas4 gene through demethylation", "gene through demethylation of", "through demethylation of hypermethylated", "demethylation of hypermethylated cpg", "of hypermethylated cpg dinucleotides", "hypermethylated cpg dinucleotides in", "cpg dinucleotides in the", "dinucleotides in the npas4", "in the npas4 gene", "the npas4 gene promoter", "npas4 gene promoter region", "promoter region rudenko", "region rudenko et", "rudenko et al. 2013", "et al. 2013 .", "al. 2013 . transcriptional", "2013 . transcriptional activation", ". transcriptional activation of", "transcriptional activation of the", "activation of the npas4", "npas4 gene is associated", "gene is associated with", "is associated with the", "associated with the appearance", "with the appearance of", "the appearance of h3k4me3", "appearance of h3k4me3 mark", "of h3k4me3 mark and", "h3k4me3 mark and 5hmc", "mark and 5hmc mark", "and 5hmc mark at", "5hmc mark at the", "mark at the npas4", "at the npas4 gene", "gene promoter webb", "promoter webb et", "webb et al. 2017", "transcription of the npas4 gene", "of the npas4 gene is", "the npas4 gene is positively", "npas4 gene is positively regulated", "gene is positively regulated by", "is positively regulated by neuronal", "positively regulated by neuronal stimulation", "regulated by neuronal stimulation related", "by neuronal stimulation related increase", "neuronal stimulation related increase in", "stimulation related increase in intracellular", "related increase in intracellular calcium", "increase in intracellular calcium levels", "intracellular calcium levels lin", "calcium levels lin et", "levels lin et al.", "et al. 2008 zhang", "al. 2008 zhang et", "2008 zhang et al.", "et al. 2009 mellstr\u00f6m", "al. 2009 mellstr\u00f6m et", "2009 mellstr\u00f6m et al.", "et al. 2014 lobos", "al. 2014 lobos et", "2014 lobos et al.", "lobos et al. 2021 .

              in", "et al. 2021 .

              in the", "al. 2021 .

              in the absence", "2021 .

              in the absence of", ".

              in the absence of neuronal", "the absence of neuronal activity", "absence of neuronal activity induced", "of neuronal activity induced calcium", "neuronal activity induced calcium influx", "induced calcium influx kcnip3", "influx kcnip3 dream", "kcnip3 dream binds", "dream binds to the", "binds to the promoter of", "to the promoter of the", "the promoter of the npas4", "promoter of the npas4 gene", "of the npas4 gene and", "the npas4 gene and represses", "npas4 gene and represses npas4", "gene and represses npas4 transcription", "represses npas4 transcription mellstr\u00f6m", "npas4 transcription mellstr\u00f6m et", "transcription mellstr\u00f6m et al.", "mellstr\u00f6m et al. 2014 .", "et al. 2014 . in", "al. 2014 . in non", "2014 . in non neuronal", ". in non neuronal cells", "non neuronal cells rest", "neuronal cells rest protein", "cells rest protein represses", "rest protein represses transcription of", "protein represses transcription of the", "represses transcription of the npas4", "the npas4 gene bersten", "npas4 gene bersten et", "gene bersten et al.", "bersten et al. 2014 .", "al. 2014 . in neuronal", "2014 . in neuronal cells", "in neuronal cells rest", "neuronal cells rest may", "cells rest may have", "rest may have a dual", "may have a dual effect", "have a dual effect on", "a dual effect on npas4", "dual effect on npas4 expression:", "effect on npas4 expression: acting", "on npas4 expression: acting as", "npas4 expression: acting as a", "expression: acting as a positive", "acting as a positive regulator", "as a positive regulator of", "a positive regulator of npas4", "positive regulator of npas4 transcription", "regulator of npas4 transcription early", "of npas4 transcription early upon", "npas4 transcription early upon neuronal", "transcription early upon neuronal excitation", "early upon neuronal excitation and", "upon neuronal excitation and as", "neuronal excitation and as a", "excitation and as a negative", "and as a negative regulator", "as a negative regulator at", "a negative regulator at later", "negative regulator at later time", "regulator at later time points", "later time points allowing", "time points allowing npas4", "points allowing npas4 to", "allowing npas4 to return to", "npas4 to return to basal", "to return to basal levels", "to basal levels prestigio", "basal levels prestigio et", "levels prestigio et al.", "prestigio et al. 2021 .", "et al. 2021 . binding", "al. 2021 . binding of", "2021 . binding of agonist", ". binding of agonist activated", "binding of agonist activated glucocorticoid", "of agonist activated glucocorticoid receptor", "agonist activated glucocorticoid receptor nr3c1", "glucocorticoid receptor nr3c1 also", "receptor nr3c1 also known", "nr3c1 also known as", "known as gr to", "as gr to evolutionarily", "gr to evolutionarily conserved", "to evolutionarily conserved glucocorticoid response", "evolutionarily conserved glucocorticoid response elements", "glucocorticoid response elements gres", "elements gres upstream", "gres upstream of the", "upstream of the npas4 gene", "of the npas4 gene transcription", "the npas4 gene transcription start", "npas4 gene transcription start site", "gene transcription start site is", "transcription start site is responsible", "start site is responsible for", "site is responsible for stress", "is responsible for stress induced", "responsible for stress induced repression", "for stress induced repression of", "stress induced repression of npas4", "induced repression of npas4 gene", "repression of npas4 gene transcription", "npas4 gene transcription furukawa", "gene transcription furukawa hibi", "transcription furukawa hibi et", "furukawa hibi et al. 2012", "hibi et al. 2012 .", "et al. 2012 . chronic", "al. 2012 . chronic restraint", "2012 . chronic restraint stress", ". chronic restraint stress as", "chronic restraint stress as well", "restraint stress as well as", "stress as well as corticosterone", "as well as corticosterone injection", "well as corticosterone injection also", "as corticosterone injection also reduce", "corticosterone injection also reduce npas4", "injection also reduce npas4 gene", "also reduce npas4 gene expression", "reduce npas4 gene expression in", "npas4 gene expression in the", "gene expression in the mouse", "expression in the mouse hippocampus", "the mouse hippocampus yun", "mouse hippocampus yun et", "hippocampus yun et al.", "yun et al. 2010 .", "et al. 2010 . though", "al. 2010 . though mechanisms", "2010 . though mechanisms remain", ". though mechanisms remain to", "though mechanisms remain to be", "mechanisms remain to be delineated", "to be delineated hdac5", "be delineated hdac5 was", "delineated hdac5 was reported", "hdac5 was reported by multiple", "was reported by multiple studies", "reported by multiple studies to", "by multiple studies to contribute", "multiple studies to contribute to", "studies to contribute to npas4", "to contribute to npas4 gene", "contribute to npas4 gene repression", "npas4 gene repression taniguchi", "gene repression taniguchi et", "repression taniguchi et al.", "et al. 2017 hashikawa", "al. 2017 hashikawa hobara", "2017 hashikawa hobara et", "hashikawa hobara et al. 2021", "et al. 2021 lv", "al. 2021 lv et", "2021 lv et al.", "et al. 2021 rein", "al. 2021 rein et", "2021 rein et al.", "rein et al. 2022 .", "et al. 2022 . in", "al. 2022 . in addition", ". in addition hdac3", "in addition hdac3 was", "addition hdac3 was reported", "hdac3 was reported as the", "was reported as the npas4", "reported as the npas4 gene", "as the npas4 gene repressor", "the npas4 gene repressor during", "npas4 gene repressor during neurodegeneration", "repressor during neurodegeneration louis", "during neurodegeneration louis sam", "neurodegeneration louis sam titus", "louis sam titus et al.", "sam titus et al. 2019", "titus et al. 2019 .

              srf", "al. 2019 .

              srf serum", "2019 .

              srf serum response", ".

              srf serum response factor", "serum response factor stimulates", "response factor stimulates npas4", "factor stimulates npas4 gene", "stimulates npas4 gene transcription upon", "npas4 gene transcription upon neuronal", "gene transcription upon neuronal excitation", "upon neuronal excitation kuzniewska", "neuronal excitation kuzniewska et", "excitation kuzniewska et al.", "et al. 2016 l\u00f6sing", "al. 2016 l\u00f6sing et", "2016 l\u00f6sing et al.", "et al. 2017 f\u00f6rstner", "al. 2017 f\u00f6rstner and", "2017 f\u00f6rstner and kn\u00f6ll", "f\u00f6rstner and kn\u00f6ll 2019 .", "and kn\u00f6ll 2019 . npas4", "kn\u00f6ll 2019 . npas4 gene", "2019 . npas4 gene transcription", ". npas4 gene transcription is", "npas4 gene transcription is positively", "gene transcription is positively regulated", "transcription is positively regulated by", "is positively regulated by pi3k/akt", "positively regulated by pi3k/akt signaling", "by pi3k/akt signaling ooe", "pi3k/akt signaling ooe et", "signaling ooe et al.", "et al. 2009 speckmann", "al. 2009 speckmann et", "2009 speckmann et al.", "al. 2016 and", "2016 and only", "and only partially dependent on", "only partially dependent on erk", "dependent on erk mapk", "erk mapk signaling", "mapk signaling bl\u00fcthgen", "signaling bl\u00fcthgen et al.", "bl\u00fcthgen et al. 2017 .", "et al. 2017 . npas4", "al. 2017 . npas4 may", "2017 . npas4 may be", ". npas4 may be one", "npas4 may be one of", "may be one of the", "be one of the egr1", "one of the egr1 target", "of the egr1 target genes", "egr1 target genes han", "target genes han et", "genes han et al.", "han et al. 2014 .", "et al. 2014 . neuronal", "al. 2014 . neuronal activity", "2014 . neuronal activity stimulation", ". neuronal activity stimulation may", "neuronal activity stimulation may trigger", "activity stimulation may trigger the", "stimulation may trigger the formation", "may trigger the formation of", "trigger the formation of dna", "the formation of dna double", "formation of dna double strand", "of dna double strand breaks", "double strand breaks dsbs", "breaks dsbs in", "dsbs in the promoters", "in the promoters of a", "the promoters of a subset", "promoters of a subset of", "of a subset of early", "a subset of early response", "subset of early response genes", "early response genes including", "response genes including fos", "fos npas4 and", "and egr1 which may", "egr1 which may contribute", "which may contribute to their", "may contribute to their transcriptional", "contribute to their transcriptional activation", "their transcriptional activation madabushi", "transcriptional activation madabushi et", "activation madabushi et al.", "madabushi et al. 2015 .", "et al. 2015 . npas4", "al. 2015 . npas4 appears", "2015 . npas4 appears to", ". npas4 appears to be", "npas4 appears to be a", "appears to be a downstream", "to be a downstream target", "be a downstream target involved", "a downstream target involved in", "downstream target involved in amyloid", "target involved in amyloid precursor", "involved in amyloid precursor protein", "amyloid precursor protein app", "protein app dependent", "app dependent regulation of", "dependent regulation of inhibitory synaptic", "regulation of inhibitory synaptic transmission", "inhibitory synaptic transmission opsomer", "synaptic transmission opsomer et", "transmission opsomer et al.", "opsomer et al. 2020 .", "et al. 2020 . tet1", "2020 . tet1 a", ". tet1 a methylcytosine", "tet1 a methylcytosine dioxygenase", "a methylcytosine dioxygenase that catalyzes", "methylcytosine dioxygenase that catalyzes oxidation", "dioxygenase that catalyzes oxidation of", "that catalyzes oxidation of 5", "catalyzes oxidation of 5 methylcytosine", "of 5 methylcytosine 5mc", "methylcytosine 5mc to", "5mc to 5 hydroxymethylcytosine", "to 5 hydroxymethylcytosine 5hmc", "hydroxymethylcytosine 5hmc and", "5hmc and promotes dna", "and promotes dna demethylation is", "promotes dna demethylation is implicated", "dna demethylation is implicated in", "demethylation is implicated in transcriptional", "is implicated in transcriptional activation", "implicated in transcriptional activation of", "in transcriptional activation of npas4", "transcriptional activation of npas4 gene", "activation of npas4 gene through", "of npas4 gene through demethylation", "npas4 gene through demethylation of", "gene through demethylation of hypermethylated", "through demethylation of hypermethylated cpg", "demethylation of hypermethylated cpg dinucleotides", "of hypermethylated cpg dinucleotides in", "hypermethylated cpg dinucleotides in the", "cpg dinucleotides in the npas4", "dinucleotides in the npas4 gene", "in the npas4 gene promoter", "the npas4 gene promoter region", "gene promoter region rudenko", "promoter region rudenko et", "region rudenko et al.", "rudenko et al. 2013 .", "et al. 2013 . transcriptional", "al. 2013 . transcriptional activation", "2013 . transcriptional activation of", ". transcriptional activation of the", "transcriptional activation of the npas4", "activation of the npas4 gene", "the npas4 gene is associated", "npas4 gene is associated with", "gene is associated with the", "is associated with the appearance", "associated with the appearance of", "with the appearance of h3k4me3", "the appearance of h3k4me3 mark", "appearance of h3k4me3 mark and", "of h3k4me3 mark and 5hmc", "h3k4me3 mark and 5hmc mark", "mark and 5hmc mark at", "and 5hmc mark at the", "5hmc mark at the npas4", "mark at the npas4 gene", "at the npas4 gene promoter", "npas4 gene promoter webb", "gene promoter webb et", "promoter webb et al.", "webb et al. 2017 ." ] }, { "record_id": "GLY_000594_1_2076", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9793242", "r hsa", "hsa 9793242", "r hsa 9793242" ] }, { "record_id": "GLY_000594_1_2076", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ 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mahajan", "of rangap1 mahajan et", "rangap1 mahajan et al.", "et al. 1997 lee", "al. 1997 lee et", "1997 lee et al.", "et al. 1998 knipscheer", "al. 1998 knipscheer et", "1998 knipscheer et al.", "et al. 2008 and", "al. 2008 and lmna", "and lmna zhang and", "lmna zhang and sarge", "and sarge 2008 affect", "sarge 2008 affect their", "2008 affect their localization", "affect their localization at the", "their localization at the nuclear", "localization at the nuclear envelope.", "at the nuclear envelope. sumoylation", "the nuclear envelope. sumoylation of", "nuclear envelope. sumoylation of nup153", "envelope. sumoylation of nup153 has", "sumoylation of nup153 has unknown", "of nup153 has unknown consequences", "has unknown consequences chow", "unknown consequences chow et", "consequences chow et al.", "chow et al. 2012 ." ] }, { "record_id": "GLY_000594_1_2077", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9692912", "r hsa", 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"them to", "to interact", "interact with", "with multiple", "multiple binding", "binding partners", "partners simultaneously", "thereby assembling", "assembling larger", "larger protein", "protein complexes", "harris bz", "bz &", "& lim", "lim wa", "wa 2001", "2001 .", ". viruses", "viruses also", "also encode", "encode pbm", "pbm containing", "proteins that", "to cellular", "cellular pdz", "pdz proteins.", "proteins. viral", "viral pbms", "pbms target", "target cellular", "proteins involved", "involved in", "in tight", "tight junction", "cell polarity", "polarity establishment", "and apoptosis", "javier rt", "rt &", "& rice", "rice ap", "ap 2011", "2011 .", "pdz domains are", "domains are protein\u2011protein", "are protein\u2011protein recognition", "protein\u2011protein recognition sequences", "sequences consisting", "consisting of 80\u201390", "of 80\u201390 amino", "80\u201390 amino acids", "amino acids that", "acids that bind", "that bind to", "bind to a", "to a 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"establishment of cellular", "of cellular polarity", "polarity and", "and signal transduction", "signal transduction pathways.", "transduction pathways. the", "pathways. the multidomain", "the multidomain structure", "multidomain structure of", "structure of pdz", "of pdz containing", "pdz containing proteins", "containing proteins enables", "proteins enables them", "enables them to", "them to interact", "to interact with", "interact with multiple", "with multiple binding", "multiple binding partners", "binding partners simultaneously", "simultaneously thereby", "thereby assembling larger", "assembling larger protein", "larger protein complexes", "complexes harris", "harris bz &", "bz & lim", "& lim wa", "lim wa 2001", "wa 2001 .", "2001 . viruses", ". viruses also", "viruses also encode", "also encode pbm", "encode pbm containing", "pbm containing proteins", "containing proteins that", "proteins that bind", "bind to cellular", "to cellular pdz", "cellular pdz proteins.", "pdz proteins. viral", "proteins. viral pbms", "viral pbms target", "pbms target cellular", "target cellular pdz", "cellular pdz containing", "containing proteins involved", "proteins involved in", "involved in tight", "in tight junction", "tight junction formation", "formation cell", "cell polarity establishment", "establishment and", "apoptosis javier", "javier rt &", "rt & rice", "& rice ap", "rice ap 2011", "ap 2011 .", "pdz domains are protein\u2011protein", "domains are protein\u2011protein recognition", "are protein\u2011protein recognition sequences", "recognition sequences consisting", "sequences consisting of", "consisting of 80\u201390 amino", "of 80\u201390 amino acids", "80\u201390 amino acids that", "amino acids that bind", "acids that bind to", "that bind to a", "bind to a pdz\u2011binding", "to a pdz\u2011binding motif", "pdz\u2011binding motif pbm", "pbm usually", "usually located at the", "located at the carboxy\u2011terminus", "at the carboxy\u2011terminus of", "the carboxy\u2011terminus of a", "carboxy\u2011terminus of a target", "of a target protein", "target protein hung", "protein hung ay", "hung ay & sheng", "ay & sheng m", "& sheng m 2002", "m 2002 gerek", "2002 gerek zn", "gerek zn et al.", "zn et al. 2009", "al. 2009 munz", "2009 munz m", "munz m et al.", "m et al. 2012", "et al. 2012 .", "al. 2012 . proteins", "2012 . proteins containing", ". proteins containing pdz", "proteins containing pdz domains", "containing pdz domains are", "pdz domains are typically", "domains are typically found", "are typically found in", "typically found in the", "found in the cell", "in the cell cytoplasm", "the cell cytoplasm or", "cell cytoplasm or in", "cytoplasm or in association", "or in association with", "in association with the", "association with the plasma", "with the plasma membrane", "the plasma membrane and", "plasma membrane and play", "membrane and play a", "and play a role", "play a role in", "a role in cell\u2011cell", "role in cell\u2011cell junction", "in cell\u2011cell junction formation", "junction formation establishment", "formation establishment of", "establishment of cellular polarity", "cellular polarity and", "polarity and signal", "and signal transduction pathways.", "signal transduction pathways. the", "transduction pathways. the multidomain", "pathways. the multidomain structure", "the multidomain structure of", "multidomain structure of pdz", "structure of pdz containing", "of pdz containing proteins", "pdz containing proteins enables", "containing proteins enables them", "proteins enables them to", "enables them to interact", "them to interact with", "to interact with multiple", "interact with multiple binding", "with multiple binding partners", "multiple binding partners simultaneously", "partners simultaneously thereby", "simultaneously thereby assembling", "thereby assembling larger protein", "assembling larger protein complexes", "protein complexes harris", "complexes harris bz", "harris bz & lim", "bz & lim wa", "& lim wa 2001", "lim wa 2001 .", "wa 2001 . viruses", "2001 . viruses also", ". viruses also encode", "viruses also encode pbm", "also encode pbm containing", "encode pbm containing proteins", "pbm containing proteins that", "containing proteins that bind", "proteins that bind to", "that bind to cellular", "bind to cellular pdz", "to cellular pdz proteins.", "cellular pdz proteins. viral", "pdz proteins. viral pbms", "proteins. viral pbms target", "viral pbms target cellular", "pbms target cellular pdz", "target cellular pdz containing", "cellular pdz containing proteins", "pdz containing proteins involved", "containing proteins involved in", "proteins involved in tight", "involved in tight junction", "in tight junction formation", "junction formation cell", "formation cell polarity", "polarity establishment and", "establishment and apoptosis", "and apoptosis javier", "apoptosis javier rt", "javier rt & rice", "rt & rice ap", "& rice ap 2011", "rice ap 2011 .", "pdz domains are protein\u2011protein recognition", "domains are protein\u2011protein recognition sequences", "protein\u2011protein recognition sequences consisting", "recognition sequences consisting of", "sequences consisting of 80\u201390", "consisting of 80\u201390 amino acids", "of 80\u201390 amino acids that", "80\u201390 amino acids that bind", "amino acids that bind to", "acids that bind to a", "that bind to a pdz\u2011binding", "bind to a pdz\u2011binding motif", "a pdz\u2011binding motif pbm", "pbm usually located", "usually located at the carboxy\u2011terminus", "located at the carboxy\u2011terminus of", "at the carboxy\u2011terminus of a", "the carboxy\u2011terminus of a target", "carboxy\u2011terminus of a target protein", "a target protein hung", "target protein hung ay", "protein hung ay &", "hung ay & sheng m", "ay & sheng m 2002", "sheng m 2002 gerek", "m 2002 gerek zn", "2002 gerek zn et", "gerek zn et al. 2009", "et al. 2009 munz", "al. 2009 munz m", "2009 munz m et", "munz m et al. 2012", "m et al. 2012 .", "et al. 2012 . proteins", "al. 2012 . proteins containing", "2012 . proteins containing pdz", ". proteins containing pdz domains", "proteins containing pdz domains are", "containing pdz domains are typically", "pdz domains are typically found", "domains are typically found in", "are typically found in the", "typically found in the cell", "found in the cell cytoplasm", "in the cell cytoplasm or", "the cell cytoplasm or in", "cell cytoplasm or in association", "cytoplasm or in association with", "or in association with the", "in association with the plasma", "association with the plasma membrane", "with the plasma membrane and", "the plasma membrane and play", "plasma membrane and play a", "membrane and play a role", "and play a role in", "play a role in cell\u2011cell", "a role in cell\u2011cell junction", "role in cell\u2011cell junction formation", "cell\u2011cell junction formation establishment", "junction formation establishment of", "formation establishment of cellular", "of cellular polarity and", "cellular polarity and signal", "polarity and signal transduction", "and signal transduction pathways. the", "signal transduction pathways. the multidomain", "transduction pathways. the multidomain structure", "pathways. the multidomain structure of", "the multidomain structure of pdz", "multidomain structure of pdz containing", "structure of pdz containing proteins", "of pdz containing proteins enables", "pdz containing proteins enables them", "containing proteins enables them to", "proteins enables them to interact", "enables them to interact with", "them to interact with multiple", "to interact with multiple binding", "interact with multiple binding partners", "with multiple binding partners simultaneously", "binding partners simultaneously thereby", "partners simultaneously thereby assembling", "simultaneously thereby assembling larger", "thereby assembling larger protein complexes", "larger protein complexes harris", "protein complexes harris bz", "complexes harris bz &", "harris bz & lim wa", "bz & lim wa 2001", "& lim wa 2001 .", "lim wa 2001 . viruses", "wa 2001 . viruses also", "2001 . viruses also encode", ". viruses also encode pbm", "viruses also encode pbm containing", "also encode pbm containing proteins", "encode pbm containing proteins that", "pbm containing proteins that bind", "containing proteins that bind to", "proteins that bind to cellular", "that bind to cellular pdz", "bind to cellular pdz proteins.", "to cellular pdz proteins. viral", "cellular pdz proteins. viral pbms", "pdz proteins. viral pbms target", "proteins. viral pbms target cellular", "viral pbms target cellular pdz", "pbms target cellular pdz containing", "target cellular pdz containing proteins", "cellular pdz containing proteins involved", "pdz containing proteins involved in", "containing proteins involved in tight", "proteins involved in tight junction", "involved in tight junction formation", "tight junction formation cell", "junction formation cell polarity", "formation cell polarity establishment", "cell polarity establishment and", "polarity establishment and apoptosis", "and apoptosis javier rt", "apoptosis javier rt &", "javier rt & rice ap", "rt & rice ap 2011", "& rice ap 2011 ." ] }, { "record_id": "GLY_000594_1_2078", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9692913", "r hsa", "hsa 9692913", "r hsa 9692913" ] }, { "record_id": "GLY_000594_1_2078", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "sars cov", "cov 1", "1 mediated", "mediated effects", "effects on", "on programmed", "programmed cell", "cell death", "sars cov 1", "cov 1 mediated", "1 mediated effects", "mediated effects on", "effects on programmed", "on programmed cell", "programmed cell death", "sars cov 1 mediated", "cov 1 mediated effects", "1 mediated effects on", "mediated effects on programmed", "effects on programmed cell", 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2018", "al. 2018 .", "2018 . apoptosis", ". apoptosis is", "apoptosis is a", "is a noninflammatory", "a noninflammatory form", "noninflammatory form of", "form of cell", "of cell death", "cell death driven", "death driven by", "driven by the", "by the initiator", "the initiator caspase\u2011mediated", "initiator caspase\u2011mediated cleavage", "caspase\u2011mediated cleavage of", "cleavage of executioner", "of executioner caspase\u20113", "executioner caspase\u20113 and", "caspase\u20113 and \u20117.", "and \u20117. it", "\u20117. it facilitates", "it facilitates degradation", "facilitates degradation of", "degradation of the", "of the cellular", "the cellular contents", "cellular contents but", "contents but these", "but these are", "these are not", "are not released", "not released to", "released to the", "to the extracellular", "the extracellular space.", "extracellular space. necroptosis", "space. necroptosis and", "necroptosis and pyroptosis", "and pyroptosis are", "pyroptosis 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contributing", "contributing to the", "to the depletion", "the depletion of", "depletion of t", "of t lymphocytes", "t lymphocytes by", "lymphocytes by apoptosis", "apoptosis yang", "al. 2005 .", "2005 . this", ". this may", "this may lead", "lead to the", "to the lymphopenia", "the lymphopenia observed", "lymphopenia observed in", "observed in sars", "in sars patients", "patients particularly", "particularly in severe", "in severe cases", "cases diao", "diao b et", "b et al.", "2020 chen", "chen z &", "z & wherry", "& wherry ej", "wherry ej 2020", "ej 2020 .", "cell death pcd", "pathways including pyroptosis", "including pyroptosis apoptosis", "apoptosis and necroptosis", "and necroptosis are", "necroptosis are induced", "are induced in infected", "induced in infected host", "in infected host cells", "infected host cells as", "host cells as an", "cells as an integral", "as an integral part", "an integral part of", "integral part of host", "part of host defense", "of host defense to", 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of executioner caspase\u20113", "of executioner caspase\u20113 and", "executioner caspase\u20113 and \u20117.", "caspase\u20113 and \u20117. it", "and \u20117. it facilitates", "\u20117. it facilitates degradation", "it facilitates degradation of", "facilitates degradation of the", "degradation of the cellular", "of the cellular contents", "the cellular contents but", "cellular contents but these", "contents but these are", "but these are not", "these are not released", "are not released to", "not released to the", "released to the extracellular", "to the extracellular space.", "the extracellular space. necroptosis", "extracellular space. necroptosis and", "space. necroptosis and pyroptosis", "necroptosis and pyroptosis are", "and pyroptosis are highly", "pyroptosis are highly inflammatory", "are highly inflammatory forms", "highly inflammatory forms of", "inflammatory forms of cell", "forms of cell death", "of cell death that", "cell death that lead", "death that lead to", "that lead 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"pore\u2011forming activity in inflammasome\u2011dependent", "activity in inflammasome\u2011dependent pyroptosis", "inflammasome\u2011dependent pyroptosis while", "pyroptosis while the", "while the mixed lineage", "the mixed lineage kinase", "mixed lineage kinase domain\u2011like", "kinase domain\u2011like mlkl", "mlkl protein functions", "protein functions as the", "functions as the executioner", "as the executioner during", "the executioner during necroptosis", "during necroptosis shi", "necroptosis shi j", "shi j et al.", "j et al. 2015", "al. 2015 upton", "2015 upton jw", "upton jw et al.", "jw et al. 2017", "et al. 2017 .", "al. 2017 . inflammation", "2017 . inflammation is", ". inflammation is a", "inflammation is a fundamental", "is a fundamental protective", "a fundamental protective mechanism", "fundamental protective mechanism in", "protective mechanism in elimination", "mechanism in elimination of", "in elimination of microorganisms", "of microorganisms and", "microorganisms 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lymphocytes by apoptosis", "by apoptosis yang", "apoptosis yang y", "et al. 2005 .", "al. 2005 . this", "2005 . this may", ". this may lead", "this may lead to", "may lead to the", "lead to the lymphopenia", "to the lymphopenia observed", "the lymphopenia observed in", "lymphopenia observed in sars", "observed in sars patients", "sars patients particularly", "patients particularly in", "particularly in severe cases", "severe cases diao", "cases diao b", "diao b et al.", "b et al. 2020", "al. 2020 chen", "2020 chen z", "chen z & wherry", "z & wherry ej", "& wherry ej 2020", "wherry ej 2020 .", "programmed cell death pcd", "death pcd pathways", "pcd pathways including", "pyroptosis apoptosis and", "and necroptosis are induced", "necroptosis are induced in", "are induced in infected host", "induced in infected host cells", "in infected host cells as", "infected host cells as an", "host cells as an integral", "cells as an integral part", "as an integral part of", "an integral part of host", "integral part of host defense", "part of host defense to", "of host defense to restrict", "host defense to restrict microbial", "defense to restrict microbial infections", "to restrict microbial infections and", "restrict microbial infections and regulate", "microbial infections and regulate inflammatory", "infections and regulate inflammatory responses", "regulate inflammatory responses reviewed", "inflammatory responses reviewed in", "responses reviewed in jorgensen", "reviewed in jorgensen i et", "in jorgensen i et al.", "jorgensen i et al. 2017", "et al. 2017 galluzzi", "al. 2017 galluzzi l", "2017 galluzzi l et", "galluzzi l et al. 2018", "l et al. 2018 .", "et al. 2018 . apoptosis", "al. 2018 . apoptosis is", "2018 . apoptosis is a", ". apoptosis is a noninflammatory", "apoptosis is a noninflammatory form", "is a noninflammatory form of", "a noninflammatory form of cell", "noninflammatory form of cell death", "form of cell death driven", "of cell death driven by", "cell death driven by the", "death driven by the initiator", "driven by the initiator caspase\u2011mediated", "by the initiator caspase\u2011mediated cleavage", "the initiator caspase\u2011mediated cleavage of", "initiator caspase\u2011mediated cleavage of executioner", "caspase\u2011mediated cleavage of executioner caspase\u20113", "cleavage of executioner caspase\u20113 and", "of executioner caspase\u20113 and \u20117.", "executioner caspase\u20113 and \u20117. it", "caspase\u20113 and \u20117. it facilitates", "and \u20117. it facilitates degradation", "\u20117. it facilitates degradation of", "it facilitates degradation of the", "facilitates degradation of the cellular", "degradation of the cellular contents", "of the cellular contents but", "the cellular contents but these", "cellular contents but these are", "contents but these are not", "but these are not released", "these are not released to", "are not released to the", "not released to the extracellular", "released to the extracellular space.", "to the extracellular space. necroptosis", "the extracellular space. necroptosis and", "extracellular space. necroptosis and pyroptosis", "space. necroptosis and pyroptosis are", "necroptosis and pyroptosis are highly", "and pyroptosis are highly inflammatory", "pyroptosis are highly inflammatory forms", "are highly inflammatory forms of", "highly inflammatory forms of cell", "inflammatory forms of cell death", "forms of cell death that", "of cell death that lead", "cell death that lead to", "death that lead to cell", "that lead to cell lysis", "lead to cell lysis and", "to cell lysis and release", "cell lysis and release of", "lysis and release of pro\u2011inflammatory", "and release of pro\u2011inflammatory cytokines", "release of pro\u2011inflammatory cytokines such", "of pro\u2011inflammatory cytokines such as", "pro\u2011inflammatory cytokines such as interleukin", "such as interleukin il", "as interleukin il \u20111\u03b2", "il \u20111\u03b2 tumour necrosis", "\u20111\u03b2 tumour necrosis factor", "necrosis factor alpha tnf\u2011\u03b1", "il6 il18 and cellular", "and cellular contents which", "cellular contents which can", "contents which can cause", "which can cause severe inflammation", "cause severe inflammation reviewed", "severe inflammation reviewed in", "inflammation reviewed in jorgensen", "et al. 2018 pasparakis", "al. 2018 pasparakis m", "2018 pasparakis m &", "pasparakis m & vandenabeele p", "m & vandenabeele p 2015", "& vandenabeele p 2015 .", "vandenabeele p 2015 . gasdermins", "2015 . gasdermins gsdms", "gasdermins gsdms exert", "gsdms exert pore\u2011forming activity", "exert pore\u2011forming activity in inflammasome\u2011dependent", "pore\u2011forming activity in inflammasome\u2011dependent pyroptosis", "in inflammasome\u2011dependent pyroptosis while", "inflammasome\u2011dependent pyroptosis while the", "pyroptosis while the mixed", "while the mixed lineage kinase", "the mixed lineage kinase domain\u2011like", "lineage kinase domain\u2011like mlkl", "domain\u2011like mlkl protein", "mlkl protein functions as", "protein functions as the executioner", "functions as the executioner during", "as the executioner during necroptosis", "executioner during necroptosis shi", "during necroptosis shi j", "necroptosis shi j et", "shi j et al. 2015", "et al. 2015 upton", "al. 2015 upton jw", "2015 upton jw et", "upton jw et al. 2017", "jw et al. 2017 .", "et al. 2017 . inflammation", "al. 2017 . inflammation is", "2017 . inflammation is a", ". inflammation is a fundamental", "inflammation is a fundamental protective", "is a fundamental protective mechanism", "a fundamental protective mechanism in", "fundamental protective mechanism in elimination", "protective mechanism in elimination of", "mechanism in elimination of microorganisms", "elimination of microorganisms and", "of microorganisms and is", "microorganisms and is normally", "and is normally tightly regulated", "is normally tightly regulated by", "normally tightly regulated by certain", "tightly regulated by certain mediators", "by certain mediators in", "certain mediators in particular", "mediators in particular il10", "in particular il10 to", "particular il10 to promote", "il10 to promote resolution", "to promote resolution of inflammation", "resolution of inflammation reviewed", "of inflammation reviewed in", "inflammation reviewed in sugimoto", "reviewed in sugimoto ma et", "in sugimoto ma et al.", "sugimoto ma et al. 2016", "ma et al. 2016 .", "et al. 2016 . microbial", "al. 2016 . microbial pathogens", "2016 . microbial pathogens are", ". microbial pathogens are able", "microbial pathogens are able to", "pathogens are able to trigger", "are able to trigger and/or", "able to trigger and/or modulate", "to trigger and/or modulate host", "trigger and/or modulate host pcd", "and/or modulate host pcd and", "modulate host pcd and inflammatory", "host pcd and inflammatory response", "pcd and inflammatory response through", "and inflammatory response through multiple", "inflammatory response through multiple mechanisms.

              this", "response through multiple mechanisms.

              this reactome", "through multiple mechanisms.

              this reactome module", "multiple mechanisms.

              this reactome module describes", "mechanisms.

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"y et al. 2018 .", "et al. 2018 . enhanced", "al. 2018 . enhanced production", "2018 . enhanced production and", ". enhanced production and release", "enhanced production and release of", "production and release of proinflammatory", "and release of proinflammatory cytokines", "release of proinflammatory cytokines leads", "of proinflammatory cytokines leads to", "proinflammatory cytokines leads to the", "cytokines leads to the cytokine", "leads to the cytokine storm", "to the cytokine storm that", "the cytokine storm that is", "cytokine storm that is considered", "storm that is considered to", "that is considered to play", "is considered to play a", "considered to play a major", "to play a major role", "play a major role in", "a major role in sars\u2011cov", "major role in sars\u2011cov type", "role in sars\u2011cov type 1and", "in sars\u2011cov type 1and 2", "sars\u2011cov type 1and 2 infections", "1and 2 infections reviewed", "2 infections reviewed in", "infections reviewed in channappanavar", "reviewed in channappanavar r &", "in channappanavar r & perlman", "channappanavar r & perlman s", "r & perlman s 2017", "perlman s 2017 yang", "s 2017 yang l", "2017 yang l et", "yang l et al. 2020", "l et al. 2020 .", "et al. 2020 . the", "al. 2020 . the module", "2020 . the module also", ". the module also describes", "the module also describes induction", "module also describes induction of", "also describes induction of apoptosis", "describes induction of apoptosis by", "induction of apoptosis by sars\u2011cov\u20111", "of apoptosis by sars\u2011cov\u20111 e", "apoptosis by sars\u2011cov\u20111 e and", "by sars\u2011cov\u20111 e and 7a", "sars\u2011cov\u20111 e and 7a proteins", "e and 7a proteins through", "and 7a proteins through their", "7a proteins through their interaction", "proteins through their interaction with", "through their interaction with anti\u2011apoptotic", "their interaction with anti\u2011apoptotic bcl2l1", "with anti\u2011apoptotic bcl2l1 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              in", ".
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              npas4 is", "2009 .

              npas4 is implicated", ".

              npas4 is implicated as", "is implicated as a", "implicated as a transcriptional", "as a transcriptional regulator", "a transcriptional regulator of", "transcriptional regulator of genes", "regulator of genes involved", "of genes involved in", "genes involved in neuronal", "involved in neuronal development", "in neuronal development such", "neuronal development such as", "development such as cdk5", "as cdk5 yun", "cdk5 yun et", "yun et al. 2013", "2013 cdk5r1", "cdk5r1 yun et", "2013 rbfox3", "neun yun", "2013 bdnf", "bdnf pruunsild et", "pruunsild et al. 2011", "al. 2011 and", "2011 and ret", "and ret sribudiani", "ret sribudiani et", "sribudiani et al. 2011", "2011 genes", "genes involved in synaptogenesis", "involved in synaptogenesis and", "in synaptogenesis and synaptic", "synaptogenesis and synaptic transmission", "and synaptic transmission such", "synaptic transmission such as", "transmission such as nptx2", "as nptx2 lin", "nptx2 lin et", "lin et al. 2008", "mdm2 yoshihara et", "yoshihara et al. 2014", "al. 2014 lv", "2014 lv et", "lv et al. 2021", "2021 fos", "fos ramamoorthi et", "ramamoorthi et al. 2011", "2011 iqsec3", "iqsec3 kim et", "kim et al. 2021", "2021 plk2", "plk2 weng et", "weng et al. 2018", "al. 2018 and", "2018 and possibly", "and possibly other genes", "other genes lin", "genes lin et", "al. 2008 shan", "2008 shan et", "shan et al. 2018", "2018 circadian", "circadian rhythm related genes", "rhythm related genes such", "related genes such as", "genes such as nampt", "as nampt west", "nampt west et", "west et al. 2013", "2013 and", "and genes involved in", "genes involved in neuroprotection", "involved in neuroprotection upon", "in neuroprotection upon injury", "neuroprotection upon injury such", "upon injury such as", "injury such as gem", "as gem takahashi", "gem takahashi et", "takahashi et al. 2021", "2021 syt10", "syt10 woitecki et", "woitecki et al. 2016", "al. 2016 and", "2016 and possibly", "other genes qiu", "genes qiu et", "qiu et al. 2013", "et al. 2013 .", "al. 2013 . in", "2013 . in pancreatic", ". in pancreatic beta", "in pancreatic beta cell", "beta cell npas4", "cell npas4 is", "npas4 is implicated as", "implicated as a regulator", "as a regulator of", "a regulator of insulin", "regulator of insulin synthesis", "of insulin synthesis under", "insulin synthesis under stress", "synthesis under stress conditions", "stress conditions sabatini", "conditions sabatini et", "sabatini et al. 2013", "et al. 2013 .

              the", "al. 2013 .

              the circadian", "2013 .

              the circadian clock", ".

              the circadian clock regulated", "circadian clock regulated gene", "clock regulated gene cry1", "regulated gene cry1 was", "gene cry1 was identified", "cry1 was identified as", "was identified as npas4", "identified as npas4 target", "as npas4 target gene", "npas4 target gene in", "target gene in sheep", "gene in sheep brain", "sheep brain west", "brain west et", "al. 2013 . the", "2013 . the dbnl", ". the dbnl gene", "dbnl gene encoding", "gene encoding drebrin", "encoding drebrin a", "drebrin a dendrytic", "a dendrytic cytoskeleton modulator", "cytoskeleton modulator was", "modulator was identified", "was identified as a", "identified as a gene", "as a gene directly", "a gene directly upregulated", "gene directly upregulated by", "directly upregulated by npas4", "by npas4 ooe", "npas4 ooe et", "et al. 2004

              npas4", "al. 2004

              npas4 is", "2004

              npas4 is expressed", "

              npas4 is expressed in", "is expressed in endothelial", "expressed in endothelial cells", "in endothelial cells and", "endothelial cells and may", "cells and may play", "and may play a", "may play a role", "play a role in", "a role in angiogenesis", "in angiogenesis esser", "angiogenesis esser et", "esser et al. 2017", "et al. 2017 .
              ", "npas4 is a basic helix", "is a basic helix loop", "a basic helix loop helix", "helix loop helix bhlh", "helix bhlh transcription", "bhlh transcription factor that", "transcription factor that needs to", "factor that needs to dimerize", "that needs to dimerize with", "needs to dimerize with another", "to dimerize with another bhlh", "dimerize with another bhlh protein", "another bhlh protein either", "bhlh protein either arnt", "either arnt arnt2 or", "arnt arnt2 or arntl", "arnt2 or arntl in", "or arntl in order", "arntl in order to", "in order to be able", "order to be able to", "to be able to bind", "be able to bind to", "able to bind to target", "to bind to target dna", "to target dna ooe", "target dna ooe et", "dna ooe et al.", "et al. 2004 ooe", "al. 2004 ooe et", "2004 ooe et al.", "ooe et al. 2009 .

              npas4", "et al. 2009 .

              npas4 is", "al. 2009 .

              npas4 is implicated", "2009 .

              npas4 is implicated as", ".

              npas4 is implicated as a", "is implicated as a transcriptional", "implicated as a transcriptional regulator", "as a transcriptional regulator of", "a transcriptional regulator of genes", "transcriptional regulator of genes involved", "regulator of genes involved in", "of genes involved in neuronal", "genes involved in neuronal development", "involved in neuronal development such", "in neuronal development such as", "neuronal development such as cdk5", "such as cdk5 yun", "as cdk5 yun et", "cdk5 yun et al.", "al. 2013 cdk5r1", "cdk5r1 yun et al.", "al. 2013 rbfox3", "neun yun et", "al. 2013 bdnf", "bdnf pruunsild et al.", "et al. 2011 and", "al. 2011 and ret", "and ret sribudiani et", "ret sribudiani et al.", "al. 2011 genes", "2011 genes involved", "genes involved in synaptogenesis and", "involved in synaptogenesis and synaptic", "in synaptogenesis and synaptic transmission", "synaptogenesis and synaptic transmission such", "and synaptic transmission such as", "synaptic transmission such as nptx2", "such as nptx2 lin", "as nptx2 lin et", "nptx2 lin et al.", "2008 mdm2", "mdm2 yoshihara et al.", "et al. 2014 lv", "al. 2014 lv et", "2014 lv et al.", "al. 2021 fos", "fos ramamoorthi et al.", "al. 2011 iqsec3", "iqsec3 kim et al.", "al. 2021 plk2", "plk2 weng et al.", "et al. 2018 and", "al. 2018 and possibly", "2018 and possibly other", "possibly other genes lin", "other genes lin et", "genes lin et al.", "et al. 2008 shan", "al. 2008 shan et", "2008 shan et al.", "al. 2018 circadian", "2018 circadian rhythm", "circadian rhythm related genes such", "rhythm related genes such as", "related genes such as nampt", "such as nampt west", "as nampt west et", "nampt west et al.", "al. 2013 and", "2013 and genes", "and genes involved in neuroprotection", "genes involved in neuroprotection upon", "involved in neuroprotection upon injury", "in neuroprotection upon injury such", "neuroprotection upon injury such as", "upon injury such as gem", "such as gem takahashi", "as gem takahashi et", "gem takahashi et al.", "al. 2021 syt10", "syt10 woitecki et al.", "et al. 2016 and", "al. 2016 and possibly", "2016 and possibly other", "possibly other genes qiu", "other genes qiu et", "genes qiu et al.", "qiu et al. 2013 .", "et al. 2013 . in", "al. 2013 . in pancreatic", "2013 . in pancreatic beta", ". in pancreatic beta cell", "pancreatic beta cell npas4", "beta cell npas4 is", "cell npas4 is implicated", "npas4 is implicated as a", "is implicated as a regulator", "implicated as a regulator of", "as a regulator of insulin", "a regulator of insulin synthesis", "regulator of insulin synthesis under", "of insulin synthesis under stress", "insulin synthesis under stress conditions", "under stress conditions sabatini", "stress conditions sabatini et", "conditions sabatini et al.", "sabatini et al. 2013 .

              the", "et al. 2013 .

              the circadian", "al. 2013 .

              the circadian clock", "2013 .

              the circadian clock regulated", ".

              the circadian clock regulated gene", "circadian clock regulated gene cry1", "clock regulated gene cry1 was", "regulated gene cry1 was identified", "gene cry1 was identified as", "cry1 was identified as npas4", "was identified as npas4 target", "identified as npas4 target gene", "as npas4 target gene in", "npas4 target gene in sheep", "target gene in sheep brain", "in sheep brain west", "sheep brain west et", "brain west et al.", "west et al. 2013 .", "et al. 2013 . the", "al. 2013 . the dbnl", "2013 . the dbnl gene", "the dbnl gene encoding", "dbnl gene encoding drebrin", "encoding drebrin a dendrytic", "drebrin a dendrytic cytoskeleton", "dendrytic cytoskeleton modulator was", "cytoskeleton modulator was identified", "modulator was identified as", "was identified as a gene", "identified as a gene directly", "as a gene directly upregulated", "a gene directly upregulated by", "gene directly upregulated by npas4", "upregulated by npas4 ooe", "by npas4 ooe et", "npas4 ooe et al.", "ooe et al. 2004

              npas4", "et al. 2004

              npas4 is", "al. 2004

              npas4 is expressed", "2004

              npas4 is expressed in", "

              npas4 is expressed in endothelial", "is expressed in endothelial cells", "expressed in endothelial cells and", "in endothelial cells and may", "endothelial cells and may play", "cells and may play a", "and may play a role", "may play a role in", "play a role in angiogenesis", "role in angiogenesis esser", "in angiogenesis esser et", "angiogenesis esser et al.", "esser et al. 2017 .
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"ventral cranial mesoderm aoto", "cranial mesoderm aoto et", "mesoderm aoto et al.", "al. 2009 the", "2009 the anterior", "the anterior head process gives", "anterior head process gives rise", "head process gives rise to", "process gives rise to the", "gives rise to the anterior", "rise to the anterior portion", "to the anterior portion of", "the anterior portion of the", "anterior portion of the notochord", "of the notochord notochord", "the notochord notochord precursors", "notochord notochord precursors give", "notochord precursors give rise to", "precursors give rise to the", "give rise to the remaining", "rise to the remaining posterior", "to the remaining posterior region", "the remaining posterior region of", "remaining posterior region of the", "posterior region of the notochord.", "region of the notochord. contribution", "of the notochord. contribution of", "the notochord. contribution of axial", "notochord. contribution of axial mesoderm", "contribution of axial mesoderm in", "of axial mesoderm in humans", "axial mesoderm in humans is", "mesoderm in humans is less", "in humans is less well", "humans is less well characterized", "less well characterized muller", "well characterized muller and", "characterized muller and o'rahilly", "muller and o'rahilly 2003 .", "o'rahilly 2003 .
              ", "2003 .
              all", ".
              all these", "
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              formation", "et al. 2019 .
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              formation of the axial", ".
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al. 2001", "et al. 2001 yamamoto", "al. 2001 yamamoto et", "2001 yamamoto et al.", "yamamoto et al. 2001 .", "et al. 2001 . tead", "al. 2001 . tead proteins", ". tead proteins inferred", "tead proteins inferred from", "proteins inferred from mouse", "from mouse homologs as", "as described by sawada et", "described by sawada et al.", "by sawada et al. 2005", "al. 2005 which", "2005 which are", "which are negatively regulated by", "are negatively regulated by the", "negatively regulated by the hippo", "regulated by the hippo signaling", "by the hippo signaling pathway", "hippo signaling pathway and", "signaling pathway and tbxt", "tbxt t brachury", "brachury inferred from", "as described by lolas et", "described by lolas et al.", "by lolas et al. 2014", "al. 2014 whose", "2014 whose expression", "whose expression is initiated prior", "expression is initiated prior to", "is initiated prior to primitive", "initiated prior to primitive streak", "prior to primitive streak formation", 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              though", "2021 .
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mukhopadhyay", "embryos in mukhopadhyay et", "in mukhopadhyay et al.", "mukhopadhyay et al. 2001", "et al. 2001 .", "al. 2001 . in", "2001 . in mouse", "in mouse eomesodermin", "eomes whose", "whose expression is activated", "expression is activated by", "is activated by nodal", "activated by nodal signaling", "by nodal signaling via", "nodal signaling via smad2", "signaling via smad2 and", "via smad2 and smad3", "smad2 and smad3 in", "and smad3 in the", "smad3 in the primitive", "in the primitive streak", "primitive streak is", "streak is required", "is required for formation", "required for formation of", "for formation of both", "formation of both mesoderm", "of both mesoderm and", "both mesoderm and endoderm", "and endoderm arnold", "endoderm arnold et", "arnold et al. 2008", "et al. 2008 .", "al. 2008 . experiments", "2008 . experiments in", ". experiments in human", "experiments in human embryonic", "in human embryonic stem", "human embryonic stem cells", "embryonic stem cells and", "stem cells and mouse", "cells and mouse embryos", "and mouse embryos indicate", "mouse embryos indicate that", "embryos indicate that eomes", "indicate that eomes is", "that eomes is a", "eomes is a core", "is a core element", "a core element of", "core element of a", "element of a gene", "of a gene regulatory", "a gene regulatory network", "gene regulatory network that", "regulatory network that specifies", "network that specifies definitive", "that specifies definitive endoderm", "specifies definitive endoderm by", "definitive endoderm by activating", "endoderm by activating expression", "by activating expression of", "activating expression of transcription", "expression of transcription factors", "of transcription factors such", "transcription factors such as", "factors such as foxa2", "such as foxa2 and", "as foxa2 and sox17", "foxa2 and sox17 which", "and sox17 which then", "sox17 which then activate", "which then activate sets", "then activate sets of", "activate sets of endodermally", "sets of endodermally expressed", "of endodermally expressed genes", "expressed genes teo", "genes teo et", "teo et al. 2011", "al. 2011 chia", "2011 chia et", "chia et al. 2019", "al. 2019 . as", "2019 . as endoderm", ". as endoderm progenitors", "as endoderm progenitors enter", "endoderm progenitors enter the", "progenitors enter the primitive", "enter the primitive streak", "the primitive streak they", "primitive streak they redistribute", "streak they redistribute e", "they redistribute e cadherin", "e cadherin cdh1", "cdh1 on their", "their surface which", "surface which may", "which may play a", "may play a role", "play a role in", "a role in sorting", "role in sorting the", "in sorting the cells", "sorting the cells into", "the cells into an", "cells into an epithelial", "into an epithelial layer", "epithelial layer inferred", "layer inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in viotti", "homologs in viotti et", "in viotti et al.", "viotti et al. 2014", "et al. 2014 .", "al. 2014 . unlike", "2014 . unlike mesoderm", "unlike mesoderm endoderm", "mesoderm endoderm progenitors", "endoderm progenitors do not", "progenitors do not undergo", "do not undergo a", "not undergo a complete", "undergo a complete epithelial", "a complete epithelial to", "complete epithelial to mesenchymal", "epithelial to mesenchymal transition", "mesenchymal transition emt", "emt inferred", "from mouse embryos and", "mouse embryos and stem", "embryos and stem cells", "and stem cells in", "stem cells in scheibner", "cells in scheibner et", "in scheibner et al.", "scheibner et al. 2021", "et al. 2021 .", "al. 2021 . they", "2021 . they do", ". they do not", "they do not switch", "do not switch cadherin", "not switch cadherin expression", "switch cadherin expression from", "cadherin expression from e", "expression from e cadherin", "cdh1 to n", "n cadherin cdh2", "cdh2 and do", "and do not require", "do not require the", "not 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              though", "al. 2021 .
              though no", "2021 .
              though no single", ".
              though no single marker", "no single marker gene", "single marker gene is", "marker gene is expressed", "gene is expressed exclusively", "is expressed exclusively in", "expressed exclusively in definitive", "exclusively in definitive endoderm", "definitive endoderm the", "endoderm the definitive", "the definitive endoderm is", "definitive endoderm is characterized", "endoderm is characterized by", "is characterized by the", "characterized by the expression", "by the expression of", "the expression of a", "expression of a combination", "of a combination of", "a combination of genes", "of genes including", "genes including foxa2", "including foxa2 sox17", "gsc and e", "cadherin cdh1 .", ". cdh1 a", "cdh1 a general", "a general marker of", "general marker of epithelial", "marker of epithelial cells", "epithelial cells and", "cells and the", "and the chemokine receptor", "the chemokine receptor cxcr4", "chemokine receptor cxcr4 are", "receptor cxcr4 are often", "cxcr4 are often used", "are often used together", "often used together as", "used together as surface", "together as surface markers", "as surface markers of", "surface markers of definitive", "markers of definitive endoderm", "definitive endoderm inferred", "endoderm inferred from", "mouse homologs in yasunaga", "homologs in yasunaga et", "in yasunaga et al.", "yasunaga et al. 2005", "et al. 2005 .", "the endoderm in mammalian embryos", "endoderm in mammalian embryos originates", "in mammalian embryos originates from", "mammalian embryos originates from two", "embryos originates from two different", "originates from two different populations", "from two different populations of", "two different populations of cells:", "different populations of cells: the", "populations of cells: the visceral", "of cells: the visceral endoderm", "the visceral endoderm which", "visceral endoderm which is", "endoderm which is present", "which is present before gastrulation", "is present before gastrulation as", "present before gastrulation as the", "before gastrulation as the hypoblast", "gastrulation as the hypoblast underlying", "as the hypoblast underlying the", "the hypoblast underlying the epiblast", "underlying the epiblast and", "the epiblast and the", "epiblast and the definitive", "the definitive endoderm which", "definitive endoderm which is", "endoderm which is derived", "which is derived from epiblast", "is derived from epiblast cells", "derived from epiblast cells ingressing", "from epiblast cells ingressing through", "epiblast cells ingressing through the", "cells ingressing through the anterior", "ingressing through the anterior most", "through the anterior most region", "the anterior most region of", "anterior most region of the", "most region of the primitive", "region of the primitive streak.", "of the primitive streak. after", "the primitive streak. after ingression", "streak. after ingression the", "after ingression the cells", "ingression the cells of", "the cells of the definitive", "cells of the definitive endoderm", "of the definitive endoderm then", "the definitive endoderm then intercalate", "definitive endoderm then intercalate with", "endoderm then intercalate with the", "then intercalate with the cells", "intercalate with the cells of", "with the cells of the", "the cells of the visceral", "cells of the visceral endoderm", "of the visceral endoderm to", "the visceral endoderm to form", "visceral endoderm to form the", "endoderm to form the embryonic", "to form the embryonic endoderm", "form the embryonic endoderm that", "the embryonic endoderm that will", "embryonic endoderm that will give", "endoderm that will give rise", "that will give rise to", "will give rise to the", "give rise to the gut", "rise to the gut and", "to the gut and visceral", "the gut and visceral organs", "gut and visceral organs associated", "and visceral organs associated with", "visceral organs associated with the", "organs associated with the gut", "associated with the gut such", "with the gut such as", "the gut such as the", "gut such as the pancreas", "such as the pancreas and", "as the pancreas and liver", "pancreas and liver reviewed", "and liver reviewed in", "liver reviewed in lewis", "reviewed in lewis and tam", "in lewis and tam 2006", "and tam 2006 nowotschin", "tam 2006 nowotschin et", "2006 nowotschin et al.", "nowotschin et al. 2019 .", "et al. 2019 . in", "al. 2019 . in the", "2019 . in the discoid", ". in the discoid human", "in the discoid human gastrula", "discoid human gastrula differs", "human gastrula differs from", "gastrula differs from the", "differs from the rodent gastrula", "from the rodent gastrula which", "the rodent gastrula which acquires", "rodent gastrula which acquires a", "gastrula which acquires a cup", "which acquires a cup shape", "cup shape the", "shape the endoderm", "the endoderm initially is organized", "endoderm initially is organized in", "initially is organized in a", "is organized in a flat", "organized in a flat epithelial", "in a flat epithelial sheet", "a flat epithelial sheet that", "flat epithelial sheet that later", "epithelial sheet that later rolls", "sheet that later rolls into", "that later rolls into a", "later rolls into a tube", "rolls into a tube to", "into a tube to form", "a tube to form the", "tube to form the gut.", "to form the gut. due", "form the gut. due to", "the gut. due to ethical", "gut. due to ethical considerations", "to ethical considerations research", "ethical considerations research on", "considerations research on gastrulation", "research on gastrulation is undertaken", "on gastrulation is undertaken primarily", "gastrulation is undertaken primarily in", "is undertaken primarily in non", "undertaken primarily in non human", "primarily in non human primate", "in non human primate species", "human primate species for", "primate species for example", "species for example bergmann", "for example bergmann et al.", "example bergmann et al. 2022", "et al. 2022 and", "al. 2022 and stem", "2022 and stem cells", "and stem cells d'amour", "stem cells d'amour et", "cells d'amour et al.", "et al. 2005 reviewed", "al. 2005 reviewed in", "2005 reviewed in salehin", "reviewed in salehin et al.", "in salehin et al. 2022", "al. 2022 which", "2022 which have", "which have provided insight into", "have provided insight into germ", "provided insight into germ layer", "insight into germ layer formation", "into germ layer formation in", "germ layer formation in human", "layer formation in human embryos.
              the", "formation in human embryos.
              the definitive", "in human embryos.
              the definitive endoderm", "human embryos.
              the definitive endoderm originates", "embryos.
              the definitive endoderm originates in", "definitive endoderm originates in the", "endoderm originates in the anterior", "originates in the anterior region", "in the anterior region of", "the anterior region of the", "anterior region of the primitive", "region of the primitive streak", "of the primitive streak where", "the primitive streak where there", "primitive streak where there are", "streak where there are high", "where there are high levels", "there are high levels of", "are high levels of nodal", "high levels of nodal signaling", "of nodal signaling inferred", "nodal signaling inferred from", "signaling inferred from mouse", "inferred from mouse embryos in", "from mouse embryos in vincent", "mouse embryos in vincent et", "embryos in vincent et al.", "in vincent et al. 2003", "et al. 2003 and", "al. 2003 and lower", "2003 and lower levels", "and lower levels of bmp", "lower levels of bmp signaling", "of bmp signaling inferred", "bmp signaling inferred from", "from mouse embryos in bachiller", "mouse embryos in bachiller et", "embryos in bachiller et al.", "in bachiller et al. 2000", "et al. 2000 and", "al. 2000 and wnt", "2000 and wnt signaling", "and wnt signaling inferred", "wnt signaling inferred from", "from mouse embryos in mukhopadhyay", "mouse embryos in mukhopadhyay et", "embryos in mukhopadhyay et al.", "in mukhopadhyay et al. 2001", "mukhopadhyay et al. 2001 .", "et al. 2001 . in", "al. 2001 . in mouse", ". in mouse eomesodermin", "mouse eomesodermin eomes", "eomes whose expression", "whose expression is activated by", "expression is activated by nodal", "is activated by nodal signaling", "activated by nodal signaling via", "by nodal signaling via smad2", "nodal signaling via smad2 and", "signaling via smad2 and smad3", "via smad2 and smad3 in", "smad2 and smad3 in the", "and smad3 in the primitive", "smad3 in the primitive streak", "the primitive streak is", "primitive streak is required", "streak is required for", "is required for formation of", "required for formation of both", "for formation of both mesoderm", "formation of both mesoderm and", "of both mesoderm and endoderm", "mesoderm and endoderm arnold", "and endoderm arnold et", "endoderm arnold et al.", "arnold et al. 2008 .", "et al. 2008 . experiments", "al. 2008 . experiments in", "2008 . experiments in human", ". experiments in human embryonic", "experiments in human embryonic stem", "in human embryonic stem cells", "human embryonic stem cells and", "embryonic stem cells and mouse", "stem cells and mouse embryos", "cells and mouse embryos indicate", "and mouse embryos indicate that", "mouse embryos indicate that eomes", "embryos indicate that eomes is", "indicate that eomes is a", "that eomes is a core", "eomes is a core element", "is a core element of", "a core element of a", "core element of a gene", "element of a gene regulatory", "of a gene regulatory network", "a gene regulatory network that", "gene regulatory network that specifies", "regulatory network that specifies definitive", "network that specifies definitive endoderm", "that specifies definitive endoderm by", "specifies definitive endoderm by activating", "definitive endoderm by activating expression", "endoderm by activating expression of", "by activating expression of transcription", "activating expression of transcription factors", "expression of transcription factors such", "of transcription factors such as", "transcription factors such as foxa2", "factors such as foxa2 and", "such as foxa2 and sox17", "as foxa2 and sox17 which", "foxa2 and sox17 which then", "and sox17 which then activate", "sox17 which then activate sets", "which then activate sets of", "then activate sets of endodermally", "activate sets of endodermally expressed", "sets of endodermally expressed genes", "endodermally expressed genes teo", "expressed genes teo et", "genes teo et al.", "et al. 2011 chia", "al. 2011 chia et", "2011 chia et al.", "chia et al. 2019 .", "et al. 2019 . as", "al. 2019 . as endoderm", "2019 . as endoderm progenitors", ". as endoderm progenitors enter", "as endoderm progenitors enter the", "endoderm progenitors enter the primitive", "progenitors enter the primitive streak", "enter the primitive streak they", "the primitive streak they redistribute", "primitive streak they redistribute e", "streak they redistribute e cadherin", "redistribute e cadherin cdh1", "cadherin cdh1 on", "cdh1 on their surface", "on their surface which", "their surface which may", "surface which may play", "which may play a role", "may play a role in", "play a role in sorting", "a role in sorting the", "role in sorting the cells", "in sorting the cells into", "sorting the cells into an", "the cells into an epithelial", "cells into an epithelial layer", "an epithelial layer inferred", "epithelial layer inferred from", "layer inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in viotti", "mouse homologs in viotti et", "homologs in viotti et al.", "in viotti et al. 2014", "viotti et al. 2014 .", "et al. 2014 . unlike", "al. 2014 . unlike mesoderm", ". unlike mesoderm endoderm", "unlike mesoderm endoderm progenitors", "mesoderm endoderm progenitors do", "endoderm progenitors do not undergo", "progenitors do not undergo a", "do not undergo a complete", "not undergo a complete epithelial", "undergo a complete epithelial to", "a complete epithelial to mesenchymal", "complete epithelial to mesenchymal transition", "to mesenchymal transition emt", "emt inferred from", "inferred from mouse embryos and", "from mouse embryos and stem", "mouse embryos and stem cells", "embryos and stem cells in", "and stem cells in scheibner", "stem cells in scheibner et", "cells in scheibner et al.", "in scheibner et al. 2021", "scheibner et al. 2021 .", "et al. 2021 . they", "al. 2021 . they do", "2021 . they do not", ". they do not switch", "they do not switch cadherin", "do not switch cadherin expression", "not switch cadherin expression from", "switch cadherin expression from e", "cadherin expression from e cadherin", "from e cadherin cdh1", "cadherin cdh1 to", "cdh1 to n cadherin", "to n cadherin cdh2", "cadherin cdh2 and", "cdh2 and do not", "and do not require the", "do not require the emt", "not require the emt transcription", "require the emt transcription factor", "the emt transcription factor snai1", "transcription factor snai1 inferred", "factor snai1 inferred from", "snai1 inferred from mouse", "from mouse homologs in scheibner", "mouse homologs in scheibner et", "homologs in scheibner et al.", "et al. 2021 . the", "al. 2021 . the endodermal", "2021 . the endodermal transcription", ". the endodermal transcription factor", "the endodermal transcription factor foxa2", "endodermal transcription factor foxa2 may", "transcription factor foxa2 may repress", "factor foxa2 may repress emt", "foxa2 may repress emt activity", "repress emt activity inferred", "emt activity inferred from", "activity inferred from the", "inferred from the mouse homolog", "from the mouse homolog in", "the mouse homolog in scheibner", "mouse homolog in scheibner et", "homolog in scheibner et al.", "scheibner et al. 2021 .
              though", "et al. 2021 .
              though no", "al. 2021 .
              though no single", "2021 .
              though no single marker", ".
              though no single marker gene", "no single marker gene is", "single marker gene is expressed", "marker gene is expressed exclusively", "gene is expressed exclusively in", "is expressed exclusively in definitive", "expressed exclusively in definitive endoderm", "in definitive endoderm the", "definitive endoderm the definitive", "endoderm the definitive endoderm", "the definitive endoderm is characterized", "definitive endoderm is characterized by", "endoderm is characterized by the", "is characterized by the expression", "characterized by the expression of", "by the expression of a", "the expression of a combination", "expression of a combination of", "of a combination of genes", "combination of genes including", "of genes including foxa2", "foxa2 sox17 gata4", "sox17 gata4 gata6", "gata4 gata6 cxcr4", "gata6 cxcr4 gsc", "cxcr4 gsc and", "gsc and e cadherin", "and e cadherin cdh1", "e cadherin cdh1 .", "cadherin cdh1 . cdh1", "cdh1 . cdh1 a", ". cdh1 a general", "cdh1 a general marker", "a general marker of epithelial", "general marker of epithelial cells", "of epithelial cells and", "epithelial cells and the", "cells and the chemokine", "and the chemokine receptor cxcr4", "the chemokine receptor cxcr4 are", "chemokine receptor cxcr4 are often", "receptor cxcr4 are often used", "cxcr4 are often used together", "are often used together as", "often used together as surface", "used together as surface markers", "together as surface markers of", "as surface markers of definitive", "surface markers of definitive endoderm", "of definitive endoderm inferred", "definitive endoderm inferred from", "endoderm inferred from mouse", "from mouse homologs in yasunaga", "mouse homologs in yasunaga et", "homologs in yasunaga et al.", "in yasunaga et al. 2005", "yasunaga et al. 2005 ." ] }, { "record_id": "GLY_000594_1_2086", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9824856", "r hsa", "hsa 9824856", "r hsa 9824856" ] }, { "record_id": "GLY_000594_1_2086", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective regulation", "regulation of", "of tlr7", "tlr7 by", "by endogenous", "endogenous ligand", "defective regulation of", "regulation of tlr7", "of tlr7 by", "tlr7 by endogenous", "by endogenous ligand", "defective regulation of tlr7", "regulation of tlr7 by", "of tlr7 by endogenous", "tlr7 by endogenous ligand", "defective regulation of tlr7 by", "regulation of tlr7 by endogenous", "of tlr7 by endogenous ligand", "activation of", "of innate", "innate immune", "immune receptors", "receptors including", "including toll", "toll like", "like receptors", "by pathogen", "pathogen associated", "associated molecular", "molecular patterns", "is crucial", "crucial in", "in the", "the host", "host defense", "defense against", "against microbial", "microbial infections.", "infections. on", "on the", "the other", "other hand", "these receptors", "receptors are", "are also", "also activated", "activated by", "by diverse", "diverse molecules", "molecules of", "of host", "host cell", "cell origin.", "origin. these", "these molecules", "molecules are", "are known", "known as", "as damage", "damage associated", "damps .", ". this", "this reactome", "reactome module", "module describes", "describes defects", "defects in", "in activation", "of tlrs", "tlrs by", "by the", "the endogenous", "endogenous ligands.", "ligands.

              damps", "

              damps are", "are released", "released from", "from necrotic", "necrotic cells", "cells or", "or secreted", "secreted from", "from activated", "activated cells", "cells in", "in response", "response to", "to tissue", "tissue damage", "damage to", "to mediate", "mediate tissue", "tissue repair", "repair by", "by promoting", "promoting inflammatory", "inflammatory responses", "reviewed by", "by piccinini", "piccinini am", "am et", "et al.", "gong t", "t et", "zindel lj", "lj et", "2020 .", ". however", "damps have", "have also", "also been", "been implicated", "implicated in", "the pathogenesis", "pathogenesis of", "of many", "many inflammatory", "inflammatory and", "and autoimmune", "autoimmune diseases", "including rheumatoid", "rheumatoid arthritis", "systemic lupus", "lupus erythematosus", "and atherosclerosis", "duffy l", "l &", "& o\u2019reilly", "o\u2019reilly sc", "sc 2016", "fukuda d", "d et", "liu j", "j et", "2022 .", ". there", "there is", "is a", "a correlation", "correlation between", "between high", "high level", "level of", "of endogenous", "endogenous tlr", "tlr ligands", "ligands and", "and different", "different chronic", "chronic inflammatory", "inflammatory conditions", "conditions in", "in human", "human subjects", "subjects and", "and mouse", "mouse models", "duvvuri b", "b &", "& lood", "lood c", "c et", "negishi h", "h et", "punnanitinont a", "a et", ". the", "the mechanism", "mechanism underlying", "underlying the", "the switch", "switch from", "from damps", "damps that", "that initiate", "initiate controlled", "controlled tissue", "to those", "those that", "that mediate", "mediate chronic", "uncontrolled inflammation", "inflammation is", "is still", "still unclear.", "unclear. studies", "studies suggest", "suggest that", "that an", "an abnormal", "abnormal increase", "increase in", "in protein", "protein citrullination", "citrullination is", "is involved", "involved in", "in disease", "disease pathophysiology", "anzilotti c", "sanchez pernaute", "pernaute o", "o et", "sokolove j", "sharma p", "p et", "olsen i", "i et", "2018 .", ". moreover", "gene polymorphisms", "polymorphisms within", "within tlrs", "tlrs may", "may predispose", "predispose to", "to the", "the abnormal", "abnormal inflammatory", "responses associated", "associated with", "with chronic", "chronic diseases", "diseases including", "including autoimmune", "devarapu sk", "sk &", "& anders", "anders hj", "hj 2018", "zhang y", "y et", "2021 .", ". for", "for example", "polymorphisms that", "that increase", "increase expression", "expression of", "tlr7 are", "are associated", "with a", "a higher", "higher risk", "risk of", "of sle", "reviewed in", "in fillatreau", "fillatreau s", "s et", ". further", "inherited genetic", "genetic variations", "variations can", "can promote", "promote autoimmune", "autoimmune responses.", "responses. for", "tlr7 y264h", "y264h was", "was identified", "identified as", "as a", "a gain", "gain of", "of function", "function mutation", "mutation in", "in a", "a patient", "patient with", "with sle", "brown gj", "gj et", ". tlr7", "y264h exhibited", "exhibited enhanced", "enhanced affinity", "affinity to", "to endogenous", "endogenous guanosine", "guanosine containing", "containing ligands", "activation of innate", "of innate immune", "innate immune receptors", "immune receptors including", "receptors including toll", "including toll like", "toll like receptors", "receptors tlrs", "by pathogen associated", "pathogen associated molecular", "associated molecular patterns", "patterns pamps", "pamps is", "is crucial in", "crucial in the", "in the host", "the host defense", "host defense against", "defense against microbial", "against microbial infections.", "microbial infections. on", "infections. on the", "on the other", "the other hand", "hand these", "these receptors are", "receptors are also", "are also activated", "also activated by", "activated by diverse", "by diverse molecules", "diverse molecules of", "molecules of host", "of host cell", "host cell origin.", "cell origin. these", "origin. these molecules", "these molecules are", "molecules are known", "are known as", "known as damage", "as damage associated", "damage associated molecular", "patterns damps", "damps . this", ". this reactome", "this reactome module", "reactome module describes", "module describes defects", "describes defects in", "defects in activation", "in activation of", "activation of tlrs", "of tlrs by", "tlrs by the", "by the endogenous", "the endogenous ligands.", "endogenous ligands.

              damps", "ligands.

              damps are", "

              damps are released", "are released from", "released from necrotic", "from necrotic cells", "necrotic cells or", "cells or secreted", "or secreted from", "secreted from activated", "from activated cells", "activated cells in", "cells in response", "in response to", "response to tissue", "to tissue damage", "tissue damage to", "damage to mediate", "to mediate tissue", "mediate tissue repair", "tissue repair by", "repair by promoting", "by promoting inflammatory", "promoting inflammatory responses", "responses reviewed", "reviewed by piccinini", "by piccinini am", "piccinini am et", "am et al.", "al. 2010", "2010 gong", "gong t et", "t et al.", "al. 2020", "2020 zindel", "zindel lj et", "lj et al.", "2020 . however", "however damps", "damps have also", "have also been", "also been implicated", "been implicated in", "implicated in the", "in the pathogenesis", "the pathogenesis of", "pathogenesis of many", "of many inflammatory", "many inflammatory and", "inflammatory and autoimmune", "and autoimmune diseases", "including rheumatoid arthritis", "arthritis ra", "systemic lupus erythematosus", "erythematosus sle", "atherosclerosis duffy", "duffy l &", "l & o\u2019reilly", "& o\u2019reilly sc", "o\u2019reilly sc 2016", "2016 fukuda", "fukuda d et", "d et al.", "al. 2019", "2019 gong", "2020 liu", "liu j et", "j et al.", "al. 2022", "2022 . there", ". there is", "there is a", "is a correlation", "a correlation between", "correlation between high", "between high level", "high level of", "level of endogenous", "of endogenous tlr", "endogenous tlr ligands", "tlr ligands and", "ligands and different", "and different chronic", "different chronic inflammatory", "chronic inflammatory conditions", "inflammatory conditions in", "conditions in human", "in human subjects", "human subjects and", "subjects and mouse", "and mouse models", "models duvvuri", "duvvuri b &", "b & lood", "& lood c", "lood c et", "c et al.", "2019 negishi", "negishi h et", "h et al.", "2019 punnanitinont", "punnanitinont a et", "a et al.", "2022 . the", ". the mechanism", "the mechanism underlying", "mechanism underlying the", "underlying the switch", "the switch from", "switch from damps", "from damps that", "damps that initiate", "that initiate controlled", "initiate controlled tissue", "controlled tissue repair", "repair to", "to those that", "those that mediate", "that mediate chronic", "chronic uncontrolled", "uncontrolled inflammation is", "inflammation is still", "is still unclear.", "still unclear. studies", "unclear. studies suggest", "studies suggest that", "suggest that an", "that an abnormal", "an abnormal increase", "abnormal increase in", "increase in protein", "in protein citrullination", "protein citrullination is", "citrullination is involved", "is involved in", "involved in disease", "in disease pathophysiology", "pathophysiology anzilotti", "anzilotti c et", "2010 sanchez", "sanchez pernaute o", "pernaute o et", "o et al.", "al. 2013", "2013 sokolove", "sokolove j et", "al. 2011", "2011 sharma", "sharma p et", "p et al.", "al. 2012", "2012 olsen", "olsen i et", "i et al.", "al. 2018", "2018 . moreover", "moreover gene", "gene polymorphisms within", "polymorphisms within tlrs", "within tlrs may", "tlrs may predispose", "may predispose to", "predispose to the", "to the abnormal", "the abnormal inflammatory", "abnormal inflammatory responses", "inflammatory responses associated", "responses associated with", "associated with chronic", "with chronic diseases", "chronic diseases including", "diseases including autoimmune", "including autoimmune diseases", "diseases devarapu", "devarapu sk &", "sk & anders", "& anders hj", "anders hj 2018", "2018 zhang", "zhang y et", "y et al.", "al. 2021", "2021 . for", ". for example", "example polymorphisms", "polymorphisms that increase", "that increase expression", "increase expression of", "expression of tlr7", "of tlr7 are", "tlr7 are associated", "are associated with", "associated with a", "with a higher", "a higher risk", "higher risk of", "risk of sle", "sle reviewed", "reviewed in fillatreau", "in fillatreau s", "fillatreau s et", "s et al.", "2021 . further", "further inherited", "inherited genetic variations", "genetic variations can", "variations can promote", "can promote autoimmune", "promote autoimmune responses.", "autoimmune responses. for", "responses. for example", "example tlr7", "tlr7 y264h was", "y264h was identified", "was identified as", "identified as a", "as a gain", "a gain of", "gain of function", "of function mutation", "function mutation in", "mutation in a", "in a patient", "a patient with", "patient with sle", "sle brown", "brown gj et", "gj et al.", "2022 . tlr7", ". tlr7 y264h", "tlr7 y264h exhibited", "y264h exhibited enhanced", "exhibited enhanced affinity", "enhanced affinity to", "affinity to endogenous", "to endogenous guanosine", "endogenous guanosine containing", "guanosine containing ligands", "ligands brown", "activation of innate immune", "of innate immune receptors", "innate immune receptors including", "immune receptors including toll", "receptors including toll like", "including toll like receptors", "like receptors tlrs", "tlrs by pathogen", "by pathogen associated molecular", "pathogen associated molecular patterns", "molecular patterns pamps", "pamps is crucial", "is crucial in the", "crucial in the host", "in the host defense", "the host defense against", "host defense against microbial", "defense against microbial infections.", "against microbial infections. on", "microbial infections. on the", "infections. on the other", "on the other hand", "other hand these", "hand these receptors", "these receptors are also", "receptors are also activated", "are also activated by", "also activated by diverse", "activated by diverse molecules", "by diverse molecules of", "diverse molecules of host", "molecules of host cell", "of host cell origin.", "host cell origin. these", "cell origin. these molecules", "origin. these molecules are", "these molecules are known", "molecules are known as", "are known as damage", "known as damage associated", "as damage associated molecular", "damage associated molecular patterns", "molecular patterns damps", "patterns damps .", "damps . this reactome", ". this reactome module", "this reactome module describes", "reactome module describes defects", "module describes defects in", "describes defects in activation", "defects in activation of", "in activation of tlrs", "activation of tlrs by", "of tlrs by the", "tlrs by the endogenous", "by the endogenous ligands.", "the endogenous ligands.

              damps", "endogenous ligands.

              damps are", "ligands.

              damps are released", "

              damps are released from", "are released from necrotic", "released from necrotic cells", "from necrotic cells or", "necrotic cells or secreted", "cells or secreted from", "or secreted from activated", "secreted from activated cells", "from activated cells in", "activated cells in response", "cells in response to", "in response to tissue", "response to tissue damage", "to tissue damage to", "tissue damage to mediate", "damage to mediate tissue", "to mediate tissue repair", "mediate tissue repair by", "tissue repair by promoting", "repair by promoting inflammatory", "by promoting inflammatory responses", "inflammatory responses reviewed", "responses reviewed by", "reviewed by piccinini am", "by piccinini am et", "piccinini am et al.", "et al. 2010", "2010 gong t", "gong t et al.", "et al. 2020", "2020 zindel lj", "zindel lj et al.", "al. 2020 .", ". however damps", "however damps have", "damps have also been", "have also been implicated", "also been implicated in", "been implicated in the", "implicated in the pathogenesis", "in the pathogenesis of", "the pathogenesis of many", "pathogenesis of many inflammatory", "of many inflammatory and", "many inflammatory and autoimmune", "inflammatory and autoimmune diseases", "autoimmune diseases including", "diseases including rheumatoid", "rheumatoid arthritis ra", "ra systemic", "lupus erythematosus sle", "sle and", "and atherosclerosis duffy", "atherosclerosis duffy l", "duffy l & o\u2019reilly", "l & o\u2019reilly sc", "& o\u2019reilly sc 2016", "sc 2016 fukuda", "2016 fukuda d", "fukuda d et al.", "et al. 2019", "2019 gong t", "2020 liu j", "liu j et al.", "et al. 2022", "al. 2022 .", "2022 . there is", ". there is a", "there is a correlation", "is a correlation between", "a correlation between high", "correlation between high level", "between high level of", "high level of endogenous", "level of endogenous tlr", "of endogenous tlr ligands", "endogenous tlr ligands and", "tlr ligands and different", "ligands and different chronic", "and different chronic inflammatory", "different chronic inflammatory conditions", "chronic inflammatory conditions in", "inflammatory conditions in human", "conditions in human subjects", "in human subjects and", "human subjects and mouse", "subjects and mouse models", "mouse models duvvuri", "models duvvuri b", "duvvuri b & lood", "b & lood c", "& lood c et", "lood c et al.", "2019 negishi h", "negishi h et al.", "2019 punnanitinont a", "punnanitinont a et al.", "2022 . the mechanism", ". the mechanism underlying", "the mechanism underlying the", "mechanism underlying the switch", "underlying the switch from", "the switch from damps", "switch from damps that", "from damps that initiate", "damps that initiate controlled", "that initiate controlled tissue", "initiate controlled tissue repair", "tissue repair to", "repair to those", "to those that mediate", "those that mediate chronic", "mediate chronic uncontrolled", "chronic uncontrolled inflammation", "uncontrolled inflammation is still", "inflammation is still unclear.", "is still unclear. studies", "still unclear. studies suggest", "unclear. studies suggest that", "studies suggest that an", "suggest that an abnormal", "that an abnormal increase", "an abnormal increase in", "abnormal increase in protein", "increase in protein citrullination", "in protein citrullination is", "protein citrullination is involved", "citrullination is involved in", "is involved in disease", "involved in disease pathophysiology", "disease pathophysiology anzilotti", "pathophysiology anzilotti c", "anzilotti c et al.", "2010 sanchez pernaute", "sanchez pernaute o et", "pernaute o et al.", "et al. 2013", "2013 sokolove j", "sokolove j et al.", "et al. 2011", "2011 sharma p", "sharma p et al.", "et al. 2012", "2012 olsen i", "olsen i et al.", "et al. 2018", "al. 2018 .", ". moreover gene", "moreover gene polymorphisms", "gene polymorphisms within tlrs", "polymorphisms within tlrs may", "within tlrs may predispose", "tlrs may predispose to", "may predispose to the", "predispose to the abnormal", "to the abnormal inflammatory", "the abnormal inflammatory responses", "abnormal inflammatory responses associated", "inflammatory responses associated with", "responses associated with chronic", "associated with chronic diseases", "with chronic diseases including", "chronic diseases including autoimmune", "diseases including autoimmune diseases", "autoimmune diseases devarapu", "diseases devarapu sk", "devarapu sk & anders", "sk & anders hj", "& anders hj 2018", "hj 2018 zhang", "2018 zhang y", "zhang y et al.", "et al. 2021", "al. 2021 .", "2021 . for example", "for example polymorphisms", "example polymorphisms that", "polymorphisms that increase expression", "that increase expression of", "increase expression of tlr7", "expression of tlr7 are", "of tlr7 are associated", "tlr7 are associated with", "are associated with a", "associated with a higher", "with a higher risk", "a higher risk of", "higher risk of sle", "of sle reviewed", "sle reviewed in", "reviewed in fillatreau s", "in fillatreau s et", "fillatreau s et al.", ". further inherited", "further inherited genetic", "inherited genetic variations can", "genetic variations can promote", "variations can promote autoimmune", "can promote autoimmune responses.", "promote autoimmune responses. for", "autoimmune responses. for example", "for example tlr7", "example tlr7 y264h", "tlr7 y264h was identified", "y264h was identified as", "was identified as a", "identified as a gain", "as a gain of", "a gain of function", "gain of function mutation", "of function mutation in", "function mutation in a", "mutation in a patient", "in a patient with", "a patient with sle", "with sle brown", "sle brown gj", "brown gj et al.", "2022 . tlr7 y264h", ". tlr7 y264h exhibited", "tlr7 y264h exhibited enhanced", "y264h exhibited enhanced affinity", "exhibited enhanced affinity to", "enhanced affinity to endogenous", "affinity to endogenous guanosine", "to endogenous guanosine containing", "endogenous guanosine containing ligands", "containing ligands brown", "ligands brown gj", "activation of innate immune receptors", "of innate immune receptors including", "innate immune receptors including toll", "immune receptors including toll like", "receptors including toll like receptors", "toll like receptors tlrs", "receptors tlrs by", "tlrs by pathogen associated", "by pathogen associated molecular patterns", "associated molecular patterns pamps", "patterns pamps is", "pamps is crucial in", "is crucial in the host", "crucial in the host defense", "in the host defense against", "the host defense against microbial", "host defense against microbial infections.", "defense against microbial infections. on", "against microbial infections. on the", "microbial infections. on the other", "infections. on the other hand", "the other hand these", "other hand these receptors", "hand these receptors are", "these receptors are also activated", "receptors are also activated by", "are also activated by diverse", "also activated by diverse molecules", "activated by diverse molecules of", "by diverse molecules of host", "diverse molecules of host cell", "molecules of host cell origin.", "of host cell origin. these", "host cell origin. these molecules", "cell origin. these molecules are", "origin. these molecules are known", "these molecules are known as", "molecules are known as damage", "are known as damage associated", "known as damage associated molecular", "as damage associated molecular patterns", "associated molecular patterns damps", "molecular patterns damps .", "patterns damps . this", "damps . this reactome module", ". this reactome module describes", "this reactome module describes defects", "reactome module describes defects in", "module describes defects in activation", "describes defects in activation of", "defects in activation of tlrs", "in activation of tlrs by", "activation of tlrs by the", "of tlrs by the endogenous", "tlrs by the endogenous ligands.", "by the endogenous ligands.

              damps", "the endogenous ligands.

              damps are", "endogenous ligands.

              damps are released", "ligands.

              damps are released from", "

              damps are released from necrotic", "are released from necrotic cells", "released from necrotic cells or", "from necrotic cells or secreted", "necrotic cells or secreted from", "cells or secreted from activated", "or secreted from activated cells", "secreted from activated cells in", "from activated cells in response", "activated cells in response to", "cells in response to tissue", "in response to tissue damage", "response to tissue damage to", "to tissue damage to mediate", "tissue damage to mediate tissue", "damage to mediate tissue repair", "to mediate tissue repair by", "mediate tissue repair by promoting", "tissue repair by promoting inflammatory", "repair by promoting inflammatory responses", "promoting inflammatory responses reviewed", "inflammatory responses reviewed by", "responses reviewed by piccinini", "reviewed by piccinini am et", "by piccinini am et al.", "am et al. 2010", "al. 2010 gong", "2010 gong t et", "t et al. 2020", "al. 2020 zindel", "2020 zindel lj et", "lj et al. 2020", "et al. 2020 .", "al. 2020 . however", "2020 . however damps", ". however damps have", "however damps have also", "damps have also been implicated", "have also been implicated in", "also been implicated in the", "been implicated in the pathogenesis", "implicated in the pathogenesis of", "in the pathogenesis of many", "the pathogenesis of many inflammatory", "pathogenesis of many inflammatory and", "of many inflammatory and autoimmune", "many inflammatory and autoimmune diseases", "and autoimmune diseases including", "autoimmune diseases including rheumatoid", "diseases including rheumatoid arthritis", "including rheumatoid arthritis ra", "ra systemic lupus", "systemic lupus erythematosus sle", "sle and atherosclerosis", "and atherosclerosis duffy l", "atherosclerosis duffy l &", "duffy l & o\u2019reilly sc", "l & o\u2019reilly sc 2016", "o\u2019reilly sc 2016 fukuda", "sc 2016 fukuda d", "2016 fukuda d et", "d et al. 2019", "al. 2019 gong", "2019 gong t et", "al. 2020 liu", "2020 liu j et", "j et al. 2022", "et al. 2022 .", "al. 2022 . there", "2022 . there is a", ". there is a correlation", "there is a correlation between", "is a correlation between high", "a correlation between high level", "correlation between high level of", "between high level of endogenous", "high level of endogenous tlr", "level of endogenous tlr ligands", "of endogenous tlr ligands and", "endogenous tlr ligands and different", "tlr ligands and different chronic", "ligands and different chronic inflammatory", "and different chronic inflammatory conditions", "different chronic inflammatory conditions in", "chronic inflammatory conditions in human", "inflammatory conditions in human subjects", "conditions in human subjects and", "in human subjects and mouse", "human subjects and mouse models", "and mouse models duvvuri", "mouse models duvvuri b", "models duvvuri b &", "duvvuri b & lood c", "b & lood c et", "& lood c et al.", "c et al. 2019", "al. 2019 negishi", "2019 negishi h et", "h et al. 2019", "al. 2019 punnanitinont", "2019 punnanitinont a et", "a et al. 2022", "al. 2022 . the", "2022 . the mechanism underlying", ". the mechanism underlying the", "the mechanism underlying the switch", "mechanism underlying the switch from", "underlying the switch from damps", "the switch from damps that", "switch from damps that initiate", "from damps that initiate controlled", "damps that initiate controlled tissue", "that initiate controlled tissue repair", "controlled tissue repair to", "tissue repair to those", "repair to those that", "to those that mediate chronic", "that mediate chronic uncontrolled", "mediate chronic uncontrolled inflammation", "chronic uncontrolled inflammation is", "uncontrolled inflammation is still unclear.", "inflammation is still unclear. studies", "is still unclear. studies suggest", "still unclear. studies suggest that", "unclear. studies suggest that an", "studies suggest that an abnormal", "suggest that an abnormal increase", "that an abnormal increase in", "an abnormal increase in protein", "abnormal increase in protein citrullination", "increase in protein citrullination is", "in protein citrullination is involved", "protein citrullination is involved in", "citrullination is involved in disease", "is involved in disease pathophysiology", "in disease pathophysiology anzilotti", "disease pathophysiology anzilotti c", "pathophysiology anzilotti c et", "c et al. 2010", "al. 2010 sanchez", "2010 sanchez pernaute o", "sanchez pernaute o et al.", "o et al. 2013", "al. 2013 sokolove", "2013 sokolove j et", "j et al. 2011", "al. 2011 sharma", "2011 sharma p et", "p et al. 2012", "al. 2012 olsen", "2012 olsen i et", "i et al. 2018", "et al. 2018 .", "al. 2018 . moreover", "2018 . moreover gene", ". moreover gene polymorphisms", "moreover gene polymorphisms within", "gene polymorphisms within tlrs may", "polymorphisms within tlrs may predispose", "within tlrs may predispose to", "tlrs may predispose to the", "may predispose to the abnormal", "predispose to the abnormal inflammatory", "to the abnormal inflammatory responses", "the abnormal inflammatory responses associated", "abnormal inflammatory responses associated with", "inflammatory responses associated with chronic", "responses associated with chronic diseases", "associated with chronic diseases including", "with chronic diseases including autoimmune", "chronic diseases including autoimmune diseases", "including autoimmune diseases devarapu", "autoimmune diseases devarapu sk", "diseases devarapu sk &", "devarapu sk & anders hj", "sk & anders hj 2018", "anders hj 2018 zhang", "hj 2018 zhang y", "2018 zhang y et", "y et al. 2021", "et al. 2021 .", "al. 2021 . for", ". for example polymorphisms", "for example polymorphisms that", "example polymorphisms that increase", "polymorphisms that increase expression of", "that increase expression of tlr7", "increase expression of tlr7 are", "expression of tlr7 are associated", "of tlr7 are associated with", "tlr7 are associated with a", "are associated with a higher", "associated with a higher risk", "with a higher risk of", "a higher risk of sle", "risk of sle reviewed", "of sle reviewed in", "sle reviewed in fillatreau", "reviewed in fillatreau s et", "in fillatreau s et al.", "s et al. 2021", "al. 2021 . further", "2021 . further inherited", ". further inherited genetic", "further inherited genetic variations", "inherited genetic variations can promote", "genetic variations can promote autoimmune", "variations can promote autoimmune responses.", "can promote autoimmune responses. for", "promote autoimmune responses. for example", "responses. for example tlr7", "for example tlr7 y264h", "example tlr7 y264h was", "tlr7 y264h was identified as", "y264h was identified as a", "was identified as a gain", "identified as a gain of", "as a gain of function", "a gain of function mutation", "gain of function mutation in", "of function mutation in a", "function mutation in a patient", 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in", "negative feedback loops in the", "feedback loops in the notch", "loops in the notch pathway", "the notch pathway which", "notch pathway which constitute", "pathway which constitute a", "which constitute a molecular oscillator", "constitute a molecular oscillator or", "a molecular oscillator or segmentation", "molecular oscillator or segmentation clock", "or segmentation clock bessho", "segmentation clock bessho et", "clock bessho et al.", "bessho et al. 2003 .", "et al. 2003 . activation", "al. 2003 . activation of", "2003 . activation of lfng", ". activation of lfng expression", "activation of lfng expression by", "of lfng expression by notch", "lfng expression by notch and", "expression by notch and inhibition", "by notch and inhibition of", "notch and inhibition of notch", "and inhibition of notch signaling", "inhibition of notch signaling by", "of notch signaling by lfng", "signaling by lfng possibly", "by lfng possibly via", "lfng possibly via regulation", "possibly via regulation of the", "via regulation of the dll3", "regulation of the dll3 ligand", "the dll3 ligand bochter", "dll3 ligand bochter et", "ligand bochter et al.", "al. 2022 constitute", "2022 constitute another", "constitute another negative feedback loop", "another negative feedback loop that", "negative feedback loop that acts", "feedback loop that acts as", "loop that acts as a", "that acts as a molecular", "acts as a molecular oscillator", "a molecular oscillator dale", "molecular oscillator dale et", "oscillator dale et al.", "et al. 2003 falk", "al. 2003 falk et", "2003 falk et al.", "falk et al. 2022 .", "et al. 2022 . clock", "al. 2022 . clock oscillations", "2022 . clock oscillations are", ". clock oscillations are initiated", "clock oscillations are initiated in", "oscillations are initiated in nascent", "are initiated in nascent presomitic", "initiated in nascent presomitic mesoderm", "in nascent presomitic mesoderm in", "nascent presomitic mesoderm in the", "presomitic 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segmentation. mesp2 activates expression", "segmentation. mesp2 activates expression of", "mesp2 activates expression of epha4", "expression of epha4 nakajima", "of epha4 nakajima et", "epha4 nakajima et al.", "al. 2006 an", "2006 an eph", "an eph receptor that participates", "eph receptor that participates in", "receptor that participates in segment", "that participates in segment boundary", "participates in segment boundary formation.", "in segment boundary formation. mesp2", "segment boundary formation. mesp2 also", "boundary formation. mesp2 also activates", "formation. mesp2 also activates expression", "mesp2 also activates expression of", "also activates expression of ripply2", "expression of ripply2 morimoto", "of ripply2 morimoto et", "ripply2 morimoto et al.", "al. 2007 an", "2007 an inhibitor", "inhibitor of tbx6 zhao", "of tbx6 zhao et", "tbx6 zhao et al.", "zhao et al. 2018 .", "et al. 2018 . tbx6", "al. 2018 . tbx6 is", "2018 . tbx6 is an", ". tbx6 is an activator", "tbx6 is an activator of", "is an activator of mesp2", "activator of mesp2 therefore", "of mesp2 therefore mesp2", "mesp2 therefore mesp2 indirectly", "therefore mesp2 indirectly inhibits its", "mesp2 indirectly inhibits its own", "indirectly inhibits its own expression", "inhibits its own expression via", "its own expression via ripply2.
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              dux4 binds hsatii", "
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              dux4 also binds", "2021 .
              dux4 also binds long", ".
              dux4 also binds long terminal", "also binds long terminal repeats", "long terminal repeats ltrs", "repeats ltrs of", "ltrs of thousands of", "of thousands of endogenous retroelements", "of endogenous retroelements notably", "endogenous retroelements notably the", "retroelements notably the hervl", "notably the hervl family of", "the hervl family of retroelements", "family of retroelements and", "of retroelements and activates", "retroelements and activates bidirectional", "and activates bidirectional transcription that", "activates bidirectional transcription that can", "bidirectional transcription that can initiate", "transcription that can initiate expression", "that can initiate expression of", "can initiate expression of adjacent", "initiate expression of adjacent genes", "of adjacent genes reviewed", "adjacent genes reviewed in", "genes reviewed in fu", "reviewed in fu et al.", "in fu et al. 2019", "et al. 2019 low", "al. 2019 low et", "2019 low et al.", "low et al. 2021 .", "et al. 2021 . interestingly", "2021 . interestingly this", ". interestingly this transcription", "interestingly this transcription of", "this transcription of endogenous retroviruses", "transcription of endogenous retroviruses evidently", "of endogenous retroviruses evidently results", "endogenous retroviruses evidently results in", "retroviruses evidently results in production", "evidently results in production of", "results in production of retrovirus", "in production of retrovirus like", "production of retrovirus like particles", "of retrovirus like particles in", "retrovirus like particles in the", "like particles in the plasma", "particles in the plasma and", "in the plasma and tissues", "the plasma and tissues of", "plasma and tissues of human", "and tissues of human embryos", "of human embryos mondal", "human embryos mondal and", "embryos mondal and hofschneider", "mondal and hofschneider 1982 .", "and hofschneider 1982 .
              dux4", "hofschneider 1982 .
              dux4 binds", "1982 .
              dux4 binds hsatii", ".
              dux4 binds hsatii pericentric", "
              dux4 binds hsatii pericentric satellite", "binds hsatii pericentric satellite repeats", "pericentric satellite repeats young", "satellite repeats young et", "repeats young et al.", "et al. 2013 hendrickson", "al. 2013 hendrickson et", "2013 hendrickson et al.", "et al. 2017 and", "al. 2017 and initiates", "2017 and initiates bidirectional", "initiates bidirectional transcription hendrickson", "bidirectional transcription hendrickson et", "transcription hendrickson et al.", "et al. 2017 shadle", "al. 2017 shadle et", "2017 shadle et al.", "shadle et al. 2019 .", "et al. 2019 . the", "al. 2019 . the transcripts", "2019 . the transcripts appear", ". the transcripts appear to", "the transcripts appear to be", "transcripts appear to be required", "appear to be required for", "to be required for subsequent", "be required for subsequent formation", "required for subsequent formation of", "for subsequent formation of chromocenters", "formation of chromocenters large", "of chromocenters large multichromosome", "chromocenters large multichromosome conglomerations", "large multichromosome conglomerations of heterochromatin", "conglomerations of heterochromatin probst", "of heterochromatin probst et", "heterochromatin probst et al.", "probst et al. 2010 .
              the", "et al. 2010 .
              the minor", "al. 2010 .
              the minor zga", "2010 .
              the minor zga is", ".
              the minor zga is followed", "minor zga is followed by", "zga is followed by the", "is followed by the major", "followed by the major zga", "by the major zga at", "the major zga at the", "major zga at the 2", "zga at the 2 cell", "at the 2 cell stage", "the 2 cell stage in", "2 cell stage in mice", "cell stage in mice and", "stage in mice and the", "in mice and the 8", "mice and the 8 cell", "and the 8 cell stage", "the 8 cell stage in", "8 cell stage in humans.", "cell stage in humans. during", "stage in humans. during the", "in humans. during the major", "humans. during the major zga", "the major zga chromatin", "major zga chromatin reverts", "zga chromatin reverts to", "chromatin reverts to a more", "reverts to a more usual", "to a more usual configuration", "more usual configuration with", "usual configuration with broad", "configuration with broad regions", "with broad regions of histone", "broad regions of histone h3", "regions of histone h3 trimethyllysine", "of histone h3 trimethyllysine 4", "histone h3 trimethyllysine 4 across", "h3 trimethyllysine 4 across genes", "trimethyllysine 4 across genes converted", "4 across genes converted to", "across genes converted to narrow", "genes converted to narrow peaks", "converted to narrow peaks near", "to narrow peaks near transcription", "narrow peaks near transcription start", "peaks near transcription start sites", "transcription start sites reviewed", "start sites reviewed in", "sites reviewed in eckersley", "2020 aoki 2022 .", "aoki 2022 . histones h3.1", "2022 . histones h3.1 and", ". histones h3.1 and h3.2", "histones h3.1 and h3.2 are", "h3.1 and h3.2 are also", "and h3.2 are also added", "h3.2 are also added at", "are also added at this", "also added at this time", "at this time ishiuchi", "this time ishiuchi et", "time ishiuchi et al.", "ishiuchi et al. 2021 ." ] }, { "record_id": "GLY_000594_1_2093", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9821993", "r hsa", "hsa 9821993", "r hsa 9821993" ] }, { "record_id": "GLY_000594_1_2093", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "replacement of", "of protamines", "protamines by", "by nucleosomes", "nucleosomes in", "in the", "the male", "male pronucleus", "replacement of protamines", "of protamines by", "protamines by nucleosomes", "by nucleosomes in", "nucleosomes in the", "in the male", "the male pronucleus", "replacement of protamines by", "of protamines by nucleosomes", "protamines by nucleosomes in", "by nucleosomes in the", "nucleosomes in the male", "in the male pronucleus", "replacement of protamines by nucleosomes", "of protamines by nucleosomes in", "protamines by nucleosomes in the", "by nucleosomes in the male", "nucleosomes in the male pronucleus", "in human", "human sperm", "about 85", "85 to", "to 90%", "90% of", "of the", "the genome", "genome is", "is associated", "associated with", "with protamines", "protamines rather", "rather than", "than histones", "reviewed in", "in torres", "torres flores", "flores and", "and hern\u00e1ndez", "hern\u00e1ndez hern\u00e1ndez", "hern\u00e1ndez 2020", "ribas maynou", "maynou et", "et al.", "al. 2022", "2022 .", ". protamines", "protamines provide", "provide a", "a much", "much higher", "higher packing", "packing density", "density of", "of dna", "dna in", "the nucleus", "nucleus but", "but there", "there are", "are few", "few reports", "reports of", "of epigenetic", "epigenetic marks", "marks on", "on protamines", "brunner et", "al. 2014", "2014 .", ". after", "after fertilization", "protamines in", "pronucleus are", "are replaced", "replaced with", "with histones", "histones provided", "provided by", "by the", "the oocyte", "oocyte cytoplasm", "in yang", "yang et", "al. 2015", "okada and", "and yamaguchi", "yamaguchi 2017", "2017 .", ". the", "the result", "result is", "is a", "a decondensation", "decondensation of", "of sperm", "sperm chromatin", "chromatin that", "that produces", "produces a", "a chromatin", "chromatin state", "state that", "that is", "is permissive", "permissive for", "for transcription.
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              nucleosomes", ".
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              nucleosomes", "2012 .
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              nucleosomes", "al. 2012 .
              nucleosomes in", "2012 .
              nucleosomes in the", ".
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"this time and persists", "time and persists until", "and persists until the", "persists until the 8", "until the 8 cell", "the 8 cell stage", "cell stage mcgraw", "stage mcgraw et", "mcgraw et al. 2006", "et al. 2006 .", "al. 2006 . in", "2006 . in mouse", ". in mouse embryos", "mouse embryos h1foo", "embryos h1foo is", "h1foo is not required", "is not required for", "not required for development", "for development s\u00e1nchez", "development s\u00e1nchez s\u00e1ez", "s\u00e1nchez s\u00e1ez et al.", "s\u00e1ez et al. 2022", "in human sperm about", "human sperm about 85", "sperm about 85 to", "about 85 to 90% of", "85 to 90% of the", "to 90% of the genome", "90% of the genome is", "of the genome is associated", "the genome is associated with", "genome is associated with protamines", "is associated with protamines rather", "associated with protamines rather than", "with protamines rather than histones", "rather than histones reviewed", "than histones reviewed in", "histones reviewed in torres", "reviewed in torres flores and", "in torres flores and hern\u00e1ndez", "torres flores and hern\u00e1ndez hern\u00e1ndez", "flores and hern\u00e1ndez hern\u00e1ndez 2020", "hern\u00e1ndez hern\u00e1ndez 2020 ribas", "hern\u00e1ndez 2020 ribas maynou", "2020 ribas maynou et", "ribas maynou et al. 2022", "maynou et al. 2022 .", "et al. 2022 . protamines", "al. 2022 . protamines provide", "2022 . protamines provide a", ". protamines provide a much", "protamines provide a much higher", "provide a much higher packing", "a much higher packing density", "much higher packing density of", "higher packing density of dna", "packing density of dna in", "density of dna in the", "of dna in the nucleus", "dna in the nucleus but", "in the nucleus but there", "the nucleus but there are", "nucleus but there are few", "but there are few reports", "there are few reports of", "are few reports of epigenetic", "few reports of epigenetic marks", "reports of epigenetic marks on", "of epigenetic marks 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              the anp arises", "2016 .
              the anp arises directly", ".
              the anp arises directly from", "anp arises directly from the", "arises directly from the epiblast", "from the epiblast requires", "the epiblast requires inhibition", "epiblast requires inhibition of", "requires inhibition of bmp signaling", "inhibition of bmp signaling by", "of bmp signaling by secreted", "bmp signaling by secreted inhibitors", "signaling by secreted inhibitors from", "by secreted inhibitors from the", "secreted inhibitors from the anterior", "inhibitors from the anterior visceral", "from the anterior visceral endoderm", "anterior visceral endoderm reviwed", "visceral endoderm reviwed in", "endoderm reviwed in andoniadou", "reviwed in andoniadou and", "in andoniadou and martinez", "andoniadou and martinez barbera", "2013 and", "and expresses sox2 driven by", "expresses sox2 driven by otx2", "driven by otx2 zic2", "otx2 zic2 and", "zic2 and pou5f1/pou3f1 bound", "and pou5f1/pou3f1 bound to the", "pou5f1/pou3f1 bound to the n2", "bound to the n2 enhancer", "to the n2 enhancer upstream", "the n2 enhancer upstream of", "n2 enhancer upstream of the", "enhancer upstream of the sox2", "upstream of the sox2 gene", "the sox2 gene inferred", "sox2 gene inferred from", "gene inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in iwafuchi", "mouse homologs in iwafuchi doi", "homologs in iwafuchi doi et", "in iwafuchi doi et al.", "iwafuchi doi et al. 2012", "doi et al. 2012 .", "et al. 2012 . the", "al. 2012 . the posterior", "2012 . the posterior part", ". the posterior part of", "the posterior part of the", "posterior part of the pnp", "part of the pnp arises", "of the pnp arises from", "the pnp arises from neuromesodermal", "pnp arises from neuromesodermal cells", "arises from neuromesodermal cells that", "from neuromesodermal cells that express", "neuromesodermal cells that express sox2", "cells that express sox2 driven", "that express sox2 driven by", "express sox2 driven by wnt", "sox2 driven by wnt and", "driven by wnt and fgf", "by wnt and fgf acting", "wnt and fgf acting through", "and fgf acting through the", "fgf acting through the n1", "acting through the n1 enhancer", "through the n1 enhancer downstream", "the n1 enhancer downstream of", "n1 enhancer downstream of the", "enhancer downstream of the sox2", "downstream of the sox2 gene", "from mouse homologs in takemoto", "mouse homologs in takemoto et", "homologs in takemoto et al.", "in takemoto et al. 2006", "takemoto et al. 2006 .
              both", "et al. 2006 .
              both the", "al. 2006 .
              both the anp", "2006 .
              both the anp and", ".
              both the anp and pnp", "the anp and pnp express", "anp and pnp express zeb2", "and pnp express zeb2 and", "pnp express zeb2 and sox1", "zeb2 and sox1 however", "and sox1 however the", "sox1 however the anp", "however the anp is characterized", "the anp is characterized by", "anp is characterized by high", "is characterized by high otx2", "characterized by high otx2 expression", "high otx2 expression simeone", "otx2 expression simeone et", "expression simeone et al.", "al. 1992 while", "1992 while the", "while the anterior pnp expresses", "the anterior pnp expresses higher", "anterior pnp expresses higher levels", "pnp expresses higher levels of", "expresses higher levels of gbx2", "levels of gbx2 inferred", "of gbx2 inferred from", "gbx2 inferred from mouse", "from mouse homologs in simeone", "mouse homologs in simeone et", "homologs in simeone et al.", "in simeone et al. 1992", "simeone et al. 1992 .", "et al. 1992 . the", "al. 1992 . the boundary", "1992 . the boundary between", ". the boundary between the", "the boundary between the anp", "boundary between the anp and", "between the anp and the", "the anp and the pnp", "anp and the pnp is", "and the pnp is partly", "the pnp is partly determined", "pnp is partly determined by", "is partly determined by a", "partly determined by a mutual", "determined by a mutual antagonism", "by a mutual antagonism between", "a mutual antagonism between otx2", "mutual antagonism between otx2 and", "antagonism between otx2 and gbx2.", "between otx2 and gbx2. otx2", "otx2 and gbx2. otx2 from", "and gbx2. otx2 from the", "gbx2. otx2 from the anp", "otx2 from the anp represses", "from the anp represses expression", "the anp represses expression of", "anp represses expression of gbx2", "represses expression of gbx2 and", "expression of gbx2 and gbx2", "of gbx2 and gbx2 from", "gbx2 and gbx2 from the", "and gbx2 from the pnp", "gbx2 from the pnp represses", "from the pnp represses expression", "the pnp represses expression of", "pnp represses expression of otx2", "expression of otx2 inferred", "of otx2 inferred from", "otx2 inferred from mouse", "from mouse homologs in wassarman", "mouse homologs in wassarman et", "homologs in wassarman et al.", "in wassarman et al. 1997", "et al. 1997 martinez\u2011barbera", "al. 1997 martinez\u2011barbera et", "1997 martinez\u2011barbera et al.", "et al. 2001 li", "al. 2001 li et", "2001 li et al.", "li et al. 2001 ." ] }, { "record_id": "GLY_000594_1_2096", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9833482", "r hsa", "hsa 9833482", "r hsa 9833482" ] }, { "record_id": "GLY_000594_1_2096", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "pkr mediated", "mediated signaling", "pkr mediated signaling", "interferon induced", "double stranded", "stranded rna", "rna activated", "activated protein", "protein kinase", "kinase pkr", "mainly halts", "halts cellular", "cellular protein", "protein translation", "translation by", "by phosphorylating", "phosphorylating eif2\u03b1", "which blocks", "blocks the", "the recycling", "recycling of", "of gdp", "gdp eif2", "eif2 to", "to gtp", "gtp eif2", "eif2 required", "required for", "for cap", "cap dependent", "dependent translation", "translation initiation.", "initiation. pkr", "pkr is", "is constitutively", "constitutively expressed", "expressed at", "at low", "low level", "and its", "its expression", "expression is", "is up", "up regulated", "regulated by", "by interferon", "interferon alpha/beta", "alpha/beta signaling.", "signaling. pkr", "is mainly", "mainly localized", "localized in", "in the", "the cytoplasm", "cytoplasm with", "with a", "a small", "small fraction", "fraction in", "the nucleus", "tian &", "& mathews", "mathews 2001", "2001 .", ".
              pkr", "
              pkr was", "was identified", "identified in", "the 1970s", "friedman et", "et al", "kerr et", "et al.", "1977 .", ". its", "its activation", "activation is", "is characterized", "characterized by", "by the", "the shifting", "shifting of", "of its", "its monomer/dimer", "monomer/dimer equilibrium", "equilibrium towards", "towards the", "the dimer", "with subsequent", "subsequent autophosphorylation", "reviewed by", "by sadler", "sadler &", "& williams", "bou nader", "nader et", "2019 .", ". possible", "possible activating", "activating factors", "factors include", "include binding", "binding of", "of viral", "viral dsrna", "dsrna to", "to the", "the pkr", "pkr dsrna", "dsrna binding", "binding domain", "by nallagatla", "nallagatla et", "as well", "well as", "as cellular", "cellular proteins", "and heparin", "patel &", "& sen", "dougherty et", "george et", "fasciano et", "by zhang", "zhang et", "2021 .", ". general", "general translation", "translation shutdown", "shutdown by", "by pkr", "pkr can", "can therefore", "therefore be", "be promoted", "promoted by", "by both", "both viral", "viral infection", "infection and", "and the", "the integrated", "integrated response", "response of", "of the", "the cell", "cell to", "to stress", "stress stimuli", "by pizzinga", "pizzinga et", "costa mattioli", "mattioli &", "& walter", "2020 .", ". several", "several cellular", "cellular inhibitors", "inhibitors of", "of pkr", "pkr activation", "activation and", "and eif2\u03b1", "eif2\u03b1 phosphorylation", "phosphorylation by", "pkr have", "have been", "been identified", "identified and", "and binding", "pkr to", "to viral", "viral proteins", "proteins from", "from rna", "rna viruses", "e.g. hiv", "influenza a", "has also", "also been", "been shown", "shown to", "to contribute", "contribute to", "to inhibition", "by cesaro", "cesaro &", "& michiels", ". in", "in addition", "addition to", "to its", "its role", "role in", "in translation", "shutdown via", "via eif2\u03b1", "pkr affects", "affects translation", "translation through", "through nfar", "nfar protein", "protein phosphorylation", "it can", "can also", "also phosphorylate", "phosphorylate rna", "rna helicase", "helicase a", "and mkk6", "thus modulating", "modulating rna", "rna metabolism", "g2 arrest", "and p38", "p38 mapk", "mapk activation.", "activation. finally", "can bind", "bind to", "to traf", "traf proteins", "the ikappab", "ikappab kinase", "kinase complex", "gsk 3beta", "and several", "several inflammasome", "inflammasome components", "components leading", "leading to", "to nf", "nf kappa", "kappa b", "b activation", "tau phosphorylation", "and inflammasome", "inflammasome activation", "by gil", "gil &", "& esteban", "garcia et", "pindel &", "& sadler", "marchal et", "yim &", "mckey et", "induced double", "double stranded rna", "stranded rna activated", "rna activated protein", "activated protein kinase", "protein kinase pkr", "pkr eif2ak2", "eif2ak2 mainly", "mainly halts cellular", "halts cellular protein", "cellular protein translation", "protein translation by", "translation by phosphorylating", "by phosphorylating eif2\u03b1", "eif2\u03b1 which", "which blocks the", "blocks the recycling", "the recycling of", "recycling of gdp", "of gdp eif2", "gdp eif2 to", "eif2 to gtp", "to gtp eif2", "gtp eif2 required", "eif2 required for", "required for cap", "for cap dependent", "cap dependent translation", "dependent translation initiation.", "translation initiation. pkr", "initiation. pkr is", "pkr is constitutively", "is constitutively expressed", "constitutively expressed at", "expressed at low", "at low level", "level and", "and its expression", "its expression is", "expression is up", "is up regulated", "up regulated by", "regulated by interferon", "by interferon alpha/beta", "interferon alpha/beta signaling.", "alpha/beta signaling. pkr", "signaling. pkr is", "pkr is mainly", "is mainly localized", "mainly localized in", "localized in the", "in the cytoplasm", "the cytoplasm with", "cytoplasm with a", "with a small", "a small fraction", "small fraction in", "fraction in the", "in the nucleus", "nucleus tian", "tian & mathews", "& mathews 2001", "mathews 2001 .", "2001 .
              pkr", ".
              pkr was", "
              pkr was identified", "was identified in", "identified in the", "in the 1970s", "1970s friedman", "friedman et al", "al 1972", "1972 kerr", "kerr et al.", "al. 1977", "1977 . its", ". its activation", "its activation is", "activation is characterized", "is characterized by", "characterized by the", "by the shifting", "the shifting of", "shifting of its", "of its monomer/dimer", "its monomer/dimer equilibrium", "monomer/dimer equilibrium towards", "equilibrium towards the", "towards the dimer", "dimer with", "with subsequent autophosphorylation", "autophosphorylation reviewed", "reviewed by sadler", "by sadler &", "sadler & williams", "williams 2007", "2007 bou", "bou nader et", "nader et al", "al 2019", "2019 . possible", ". possible activating", "possible activating factors", "activating factors include", "factors include binding", "include binding of", "binding of viral", "of viral dsrna", "viral dsrna to", "dsrna to the", "to the pkr", "the pkr dsrna", "pkr dsrna binding", "dsrna binding domain", "domain reviewed", "reviewed by nallagatla", "by nallagatla et", "nallagatla et al", "al 2011", "as well as", "well as cellular", "as cellular proteins", "proteins isg15", "isg15 pact", "pact dcp1a", "dcp1a and", "heparin patel", "patel & sen", "sen 1998", "1998 dougherty", "dougherty et al.", "al. 2014", "2014 george", "george et al.", "al. 1996", "1996 fasciano", "fasciano et al.", "al. 2005", "2005 reviewed", "reviewed by zhang", "by zhang et", "zhang et al", "al 2021", "2021 . general", ". general translation", "general translation shutdown", "translation shutdown by", "shutdown by pkr", "by pkr can", "pkr can therefore", "can therefore be", "therefore be promoted", "be promoted by", "promoted by both", "by both viral", "both viral infection", "viral infection and", "infection and the", "and the integrated", "the integrated response", "integrated response of", "response of the", "of the cell", "the cell to", "cell to stress", "to stress stimuli", "stimuli reviewed", "reviewed by pizzinga", "by pizzinga et", "pizzinga et al", "2019 costa", "costa mattioli &", "mattioli & walter", "walter 2020", "2020 . several", ". several cellular", "several cellular inhibitors", "cellular inhibitors of", "inhibitors of pkr", "of pkr activation", "pkr activation and", "activation and eif2\u03b1", "and eif2\u03b1 phosphorylation", "eif2\u03b1 phosphorylation by", "phosphorylation by pkr", "by pkr have", "pkr have been", "have been identified", "been identified and", "identified and binding", "and binding of", "binding of pkr", "of pkr to", "pkr to viral", "to viral proteins", "viral proteins from", "proteins from rna", "from rna viruses", "viruses e.g.", "hiv influenza", "a rsv", "rsv has", "has also been", "also been shown", "been shown to", "shown to contribute", "to contribute to", "contribute to inhibition", "inhibition reviewed", "reviewed by cesaro", "by cesaro &", "cesaro & michiels", "michiels 2021", "2021 . in", ". in addition", "in addition to", "addition to its", "to its role", "its role in", "role in translation", "in translation shutdown", "translation shutdown via", "shutdown via eif2\u03b1", "eif2\u03b1 pkr", "pkr affects translation", "affects translation through", "translation through nfar", "through nfar protein", "nfar protein phosphorylation", "phosphorylation it", "it can also", "can also phosphorylate", "also phosphorylate rna", "phosphorylate rna helicase", "rna helicase a", "a cdc2", "cdc2 and", "mkk6 thus", "thus modulating rna", "modulating rna metabolism", "metabolism g2", "arrest and", "and p38 mapk", "p38 mapk activation.", "mapk activation. finally", "finally pkr", "pkr can bind", "can bind to", "bind to traf", "to traf proteins", "proteins the", "the ikappab kinase", "ikappab kinase complex", "complex gsk", "3beta and", "and several inflammasome", "several inflammasome components", "inflammasome components leading", "components leading to", "leading to nf", "to nf kappa", "nf kappa b", "kappa b activation", "activation tau", "phosphorylation apoptosis", "apoptosis and", "and inflammasome activation", "activation reviewed", "reviewed by gil", "by gil &", "gil & esteban", "esteban 2000", "2000 garcia", "garcia et al", "al 2007", "2007 pindel", "pindel & sadler", "sadler 2011", "2011 marchal", "marchal et al", "al 2014", "2014 yim", "yim & williams", "williams 2014", "2014 mckey", "mckey et al", "interferon induced double", "induced double stranded", "double stranded rna activated", "stranded rna activated protein", "rna activated protein kinase", "activated protein kinase pkr", "kinase pkr eif2ak2", "eif2ak2 mainly halts", "mainly halts cellular protein", "halts cellular protein translation", "cellular protein translation by", "protein translation by phosphorylating", "translation by phosphorylating eif2\u03b1", "phosphorylating eif2\u03b1 which", "eif2\u03b1 which blocks", "which blocks the recycling", "blocks the recycling of", "the recycling of gdp", "recycling of gdp eif2", "of gdp eif2 to", "gdp eif2 to gtp", "eif2 to gtp eif2", "to gtp eif2 required", "gtp eif2 required for", "eif2 required for cap", "required for cap dependent", "for cap dependent translation", "cap dependent translation initiation.", "dependent translation initiation. pkr", "translation initiation. pkr is", "initiation. pkr is constitutively", "pkr is constitutively expressed", "is constitutively expressed at", "constitutively expressed at low", "expressed at low level", "low level and", "level and its", "and its expression is", "its expression is up", "expression is up regulated", "is up regulated by", "up regulated by interferon", "regulated by interferon alpha/beta", "by interferon alpha/beta signaling.", "interferon alpha/beta signaling. pkr", "alpha/beta signaling. pkr is", "signaling. pkr is mainly", "pkr is mainly localized", "is mainly localized in", "mainly localized in the", "localized in the cytoplasm", "in the cytoplasm with", "the cytoplasm with a", "cytoplasm with a small", "with a small fraction", "a small fraction in", "small fraction in the", "fraction in the nucleus", "the nucleus tian", "nucleus tian &", "tian & mathews 2001", "& mathews 2001 .", "mathews 2001 .
              pkr", "2001 .
              pkr was", ".
              pkr was identified", "
              pkr was identified in", "was identified in the", "identified in the 1970s", "the 1970s friedman", "1970s friedman et", "et al 1972", "1972 kerr et", "et al. 1977", "al. 1977 .", "1977 . its activation", ". its activation is", "its activation is characterized", "activation is characterized by", "is characterized by the", "characterized by the shifting", "by the shifting of", "the shifting of its", "shifting of its monomer/dimer", "of its monomer/dimer equilibrium", "its monomer/dimer equilibrium towards", "monomer/dimer equilibrium towards the", "equilibrium towards the dimer", "the dimer with", "dimer with subsequent", "subsequent autophosphorylation reviewed", "autophosphorylation reviewed by", "reviewed by sadler &", "by sadler & williams", "& williams 2007", "2007 bou nader", "bou nader et al", "et al 2019", "al 2019 .", "2019 . possible activating", ". possible activating factors", "possible activating factors include", "activating factors include binding", "factors include binding of", "include binding of viral", "binding of viral dsrna", "of viral dsrna to", "viral dsrna to the", "dsrna to the pkr", "to the pkr dsrna", "the pkr dsrna binding", "pkr dsrna binding domain", "binding domain reviewed", "domain reviewed by", "reviewed by nallagatla et", "by nallagatla et al", "et al 2011", "2011 as", "as well as cellular", "well as cellular proteins", "cellular proteins isg15", "dcp1a and heparin", "and heparin patel", "heparin patel &", "& sen 1998", "1998 dougherty et", "et al. 2014", "2014 george et", "et al. 1996", "1996 fasciano et", "et al. 2005", "2005 reviewed by", "reviewed by zhang et", "by zhang et al", "et al 2021", "al 2021 .", "2021 . general translation", ". general translation shutdown", "general translation shutdown by", "translation shutdown by pkr", "shutdown by pkr can", "by pkr can therefore", "pkr can therefore be", "can therefore be promoted", "therefore be promoted by", "be promoted by both", "promoted by both viral", "by both viral infection", "both viral infection and", "viral infection and the", "infection and the integrated", "and the integrated response", "the integrated response of", "integrated response of the", "response of the cell", "of the cell to", "the cell to stress", "cell to stress stimuli", "stress stimuli reviewed", "stimuli reviewed by", "reviewed by pizzinga et", "by pizzinga et al", "2019 costa mattioli", "costa mattioli & walter", "& walter 2020", "walter 2020 .", "2020 . several cellular", ". several cellular inhibitors", "several cellular inhibitors of", "cellular inhibitors of pkr", "inhibitors of pkr activation", "of pkr activation and", "pkr activation and eif2\u03b1", "activation and eif2\u03b1 phosphorylation", "and eif2\u03b1 phosphorylation by", "eif2\u03b1 phosphorylation by pkr", "phosphorylation by pkr have", "by pkr have been", "pkr have been identified", "have been identified and", "been identified and binding", "identified and binding of", "and binding of pkr", "binding of pkr to", "of pkr to viral", "pkr to viral proteins", "to viral proteins from", "viral proteins from rna", "proteins from rna viruses", "rna viruses e.g.", "viruses e.g. hiv", "e.g. hiv influenza", "hiv influenza a", "influenza a rsv", "rsv has also", "has also been shown", "also been shown to", "been shown to contribute", "shown to contribute to", "to contribute to inhibition", "to inhibition reviewed", "inhibition reviewed by", "reviewed by cesaro &", "by cesaro & michiels", "& michiels 2021", "michiels 2021 .", "2021 . in addition", ". in addition to", "in addition to its", "addition to its role", "to its role in", "its role in translation", "role in translation shutdown", "in translation shutdown via", "translation shutdown via eif2\u03b1", "via eif2\u03b1 pkr", "eif2\u03b1 pkr affects", "pkr affects translation through", "affects translation through nfar", "translation through nfar protein", "through nfar protein phosphorylation", "protein phosphorylation it", "phosphorylation it can", "it can also phosphorylate", "can also phosphorylate rna", "also phosphorylate rna helicase", "phosphorylate rna helicase a", "helicase a cdc2", "cdc2 and mkk6", "and mkk6 thus", "mkk6 thus modulating", "thus modulating rna metabolism", "rna metabolism g2", "metabolism g2 arrest", "g2 arrest and", "arrest and p38", "and p38 mapk activation.", "p38 mapk activation. finally", "activation. finally pkr", "finally pkr can", "pkr can bind to", "can bind to traf", "bind to traf proteins", "traf proteins the", "proteins the ikappab", "the ikappab kinase complex", "kinase complex gsk", "complex gsk 3beta", "gsk 3beta and", "3beta and several", "and several inflammasome components", "several inflammasome components leading", "inflammasome components leading to", "components leading to nf", "leading to nf kappa", "to nf kappa b", "nf kappa b activation", "b activation tau", "activation tau phosphorylation", "tau phosphorylation apoptosis", "apoptosis and inflammasome", "inflammasome activation reviewed", "activation reviewed by", "reviewed by gil &", "by gil & esteban", "& esteban 2000", "2000 garcia et", "et al 2007", "2007 pindel &", "& sadler 2011", "2011 marchal et", "et al 2014", "2014 yim &", "& williams 2014", "2014 mckey et", "interferon induced double stranded", "induced double stranded rna", "double stranded rna activated protein", "stranded rna activated protein kinase", "rna activated protein kinase pkr", "protein kinase pkr eif2ak2", "pkr eif2ak2 mainly", "eif2ak2 mainly halts cellular", "mainly halts cellular protein translation", "halts cellular protein translation by", "cellular protein translation by phosphorylating", "protein translation by phosphorylating eif2\u03b1", "by phosphorylating eif2\u03b1 which", "phosphorylating eif2\u03b1 which blocks", "eif2\u03b1 which blocks the", "which blocks the recycling of", "blocks the recycling of gdp", "the recycling of gdp eif2", "recycling of gdp eif2 to", "of gdp eif2 to gtp", "gdp eif2 to gtp eif2", "eif2 to gtp eif2 required", "to gtp eif2 required for", "gtp eif2 required for cap", "eif2 required for cap dependent", "required for cap dependent translation", "for cap dependent translation initiation.", "cap dependent translation initiation. pkr", "dependent translation initiation. pkr is", "translation initiation. pkr is constitutively", "initiation. pkr is constitutively expressed", "pkr is constitutively expressed at", "is constitutively expressed at low", "constitutively expressed at low level", "at low level and", "low level and its", "level and its expression", "and its expression is up", "its expression is up regulated", "expression is up regulated by", "is up regulated by interferon", "up regulated by interferon alpha/beta", "regulated by interferon alpha/beta signaling.", "by interferon alpha/beta signaling. pkr", "interferon alpha/beta signaling. pkr is", "alpha/beta signaling. pkr is mainly", "signaling. pkr is mainly localized", "pkr is mainly localized in", "is mainly localized in the", "mainly localized in the cytoplasm", "localized in the cytoplasm with", "in the cytoplasm with a", "the cytoplasm with a small", "cytoplasm with a small fraction", "with a small fraction in", "a small fraction in the", "small fraction in the nucleus", "in the nucleus tian", "the nucleus tian &", "nucleus tian & mathews", "tian & mathews 2001 .", "& mathews 2001 .
              pkr", "mathews 2001 .
              pkr was", "2001 .
              pkr was identified", ".
              pkr was identified in", "
              pkr was identified in the", "was identified in the 1970s", "in the 1970s friedman", "the 1970s friedman et", "1970s friedman et al", "friedman et al 1972", "al 1972 kerr", "1972 kerr et al.", "kerr et al. 1977", "et al. 1977 .", "al. 1977 . its", "1977 . its activation is", ". its activation is characterized", "its activation is characterized by", "activation is characterized by the", "is characterized by the shifting", "characterized by the shifting of", "by the shifting of its", "the shifting of its monomer/dimer", "shifting of its monomer/dimer equilibrium", "of its monomer/dimer equilibrium towards", "its monomer/dimer equilibrium towards the", "monomer/dimer equilibrium towards the dimer", "towards the dimer with", "the dimer with subsequent", "dimer with subsequent autophosphorylation", "with subsequent autophosphorylation reviewed", "subsequent autophosphorylation reviewed by", "autophosphorylation reviewed by sadler", "reviewed by sadler & williams", "sadler & williams 2007", "williams 2007 bou", "2007 bou nader et", "nader et al 2019", "et al 2019 .", "al 2019 . possible", "2019 . possible activating factors", ". possible activating factors include", "possible activating factors include binding", "activating factors include binding of", "factors include binding of viral", "include binding of viral dsrna", "binding of viral dsrna to", "of viral dsrna to the", "viral dsrna to the pkr", "dsrna to the pkr dsrna", "to the pkr dsrna binding", "the pkr dsrna binding domain", "dsrna binding domain reviewed", "binding domain reviewed by", "domain reviewed by nallagatla", "reviewed by nallagatla et al", "nallagatla et al 2011", "2011 as well", "as well as cellular proteins", "as cellular proteins isg15", "proteins isg15 pact", "isg15 pact dcp1a", "pact dcp1a and", "and heparin patel &", "heparin patel & sen", "patel & sen 1998", "sen 1998 dougherty", "1998 dougherty et al.", "dougherty et al. 2014", "al. 2014 george", "2014 george et al.", "george et al. 1996", "al. 1996 fasciano", "1996 fasciano et al.", "fasciano et al. 2005", "al. 2005 reviewed", "2005 reviewed by zhang", "reviewed by zhang et al", "zhang et al 2021", "et al 2021 .", "al 2021 . general", "2021 . general translation shutdown", ". general translation shutdown by", "general translation shutdown by pkr", "translation shutdown by pkr can", "shutdown by pkr can therefore", "by pkr can therefore be", "pkr can therefore be promoted", "can therefore be promoted by", "therefore be promoted by both", "be promoted by both viral", "promoted by both viral infection", "by both viral infection and", "both viral infection and the", "viral infection and the integrated", "infection and the integrated response", "and the integrated response of", "the integrated response of the", "integrated response of the cell", "response of the cell to", "of the cell to stress", "the cell to stress stimuli", "to stress stimuli reviewed", "stress stimuli reviewed by", "stimuli reviewed by pizzinga", "reviewed by pizzinga et al", "pizzinga et al 2019", "al 2019 costa", "2019 costa mattioli &", "mattioli & walter 2020", "& walter 2020 .", "walter 2020 . several", "2020 . several cellular inhibitors", ". several cellular inhibitors of", "several cellular inhibitors of pkr", "cellular inhibitors of pkr activation", "inhibitors of pkr activation and", "of pkr activation and eif2\u03b1", "pkr activation and eif2\u03b1 phosphorylation", "activation and eif2\u03b1 phosphorylation by", "and eif2\u03b1 phosphorylation by pkr", "eif2\u03b1 phosphorylation by pkr have", "phosphorylation by pkr have been", "by pkr have been identified", "pkr have been identified and", "have been identified and binding", "been identified and binding of", "identified and binding of pkr", "and binding of pkr to", "binding of pkr to viral", "of pkr to viral proteins", "pkr to viral proteins from", "to viral proteins from rna", "viral proteins from rna viruses", "from rna viruses e.g.", "rna viruses e.g. hiv", "e.g. hiv influenza a", "a rsv has", "rsv has also been", "has also been shown to", "also been shown to contribute", "been shown to contribute to", "shown to contribute to inhibition", "contribute to inhibition reviewed", "to inhibition reviewed by", "inhibition reviewed by cesaro", "reviewed by cesaro & michiels", "cesaro & michiels 2021", "& michiels 2021 .", "michiels 2021 . in", "2021 . in addition to", ". in addition to its", "in addition to its role", "addition to its role in", "to its role in translation", "its role in translation shutdown", "role in translation shutdown via", "in translation shutdown via eif2\u03b1", "shutdown via eif2\u03b1 pkr", "via eif2\u03b1 pkr affects", "eif2\u03b1 pkr affects translation", "pkr affects translation through nfar", "affects translation through nfar protein", "translation through nfar protein phosphorylation", "nfar protein phosphorylation it", "protein phosphorylation it can", "phosphorylation it can also", "it can also phosphorylate rna", "can also phosphorylate rna helicase", "also phosphorylate rna helicase a", "rna helicase a cdc2", "a cdc2 and", "and mkk6 thus modulating", "mkk6 thus modulating rna", "modulating rna metabolism g2", "rna metabolism g2 arrest", "g2 arrest and p38", "arrest and p38 mapk", "and p38 mapk activation. finally", "mapk activation. finally pkr", "activation. finally pkr can", "finally pkr can bind", "pkr can bind to traf", "can bind to traf proteins", "to traf proteins the", "traf proteins the ikappab", "proteins the ikappab kinase", "ikappab kinase complex gsk", "kinase complex gsk 3beta", "gsk 3beta and several", "3beta and several inflammasome", "and several inflammasome components leading", "several inflammasome components leading to", "inflammasome components leading to nf", "components leading to nf kappa", "leading to nf kappa b", "to nf kappa b activation", "kappa b activation tau", "b activation tau phosphorylation", "phosphorylation apoptosis and", "apoptosis and inflammasome 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"membrane to experience high curvature", "to experience high curvature topologies", "high curvature topologies which", "curvature topologies which is", "topologies which is essential", "which is essential in many", "is essential in many neuronal", "essential in many neuronal cells.", "in many neuronal cells. degradation", "many neuronal cells. degradation of", "neuronal cells. degradation of complex", "cells. degradation of complex polysialylgangliosides", "degradation of complex polysialylgangliosides starts", "of complex polysialylgangliosides starts during", "complex polysialylgangliosides starts during endocytosis", "polysialylgangliosides starts during endocytosis producing", "starts during endocytosis producing gm1.", "during endocytosis producing gm1. inward", "endocytosis producing gm1. inward budding", "producing gm1. inward budding of", "gm1. inward budding of the", "inward budding of the late", "budding of the late endosomal", "of the late endosomal membrane", "the late 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b", "b rna", "rna that", "are antisense", "to the", "the coding", "coding mrnas", "mrnas mt", "mt nd5", "nd5 and", "mt cyb", "mt cytb", "rackham et", "2011 .", ". the", "the l", "strand and", "and h", "strand transcripts", "transcripts are", "are complementary", "complementary and", "have the", "the potential", "potential to", "to form", "form large", "large double", "double stranded", "stranded rnas", "yet very", "very little", "little dsrna", "dsrna is", "is observed", "observed in", "in wild", "wild type", "type mitochondria.
              both", "mitochondria.
              both dsrnas", "dsrnas and", "and normal", "normal mrnas", "rrnas are", "are hydrolyzed", "hydrolyzed by", "by the", "the supv3l1:pnpt1", "supv3l1:pnpt1 complex", "called the", "the degradosome", "is located", "located mostly", "mostly in", "in mitochondrial", "rna granules", "adjacent to", "the dna", "dna containing", "containing nucleoid", "in borowski", "borowski et", "al. 2010", "rorbach and", "and minczuk", "minczuk 2012", "kotrys and", "and szczesny", "szczesny 2019", ". degradation", "degradation appears", "appears to", "to occur", "occur in", "in subregions", "subregions of", "of mrgs", "mrgs called", "called d", "d foci", "al. 2013", "van haute", "haute et", "al. 2015", "2015 .", ". supv3l1", "supv3l1 is", "is a", "a helicase", "helicase that", "that unwinds", "unwinds double", "stranded rna", "shu et", "al. 2004", "wang et", "al. 2009", "dhir et", "al. 2018", "jain et", "al. 2022", "to provide", "provide single", "single stranded", "stranded substrate", "substrate to", "the pnpt1", "pnpt1 exonuclease", "lin et", "al. 2012", "2012 .", ". additionally", "g quadruplex", "quadruplex structures", "structures in", "in a", "a subset", "subset of", "of rnas", "rnas are", "are unwound", "unwound by", "by grsf1", "grsf1 to", "provide substrates", "substrates to", "antonicka et", "pietras et", "2018 .", ". however", "other rnas", "are stabilized", "stabilized by", "2013 .", "pnpt1 3'", "3' 5'", "5' exonuclease", "exonuclease hydrolyzes", "hydrolyzes rnas", "rnas to", "to yield", "yield 4", "4 5", "5 nucleotide", "nucleotide \\nanornas\\", "\\nanornas\\ which", "which are", "are further", "further hydrolyzed", "hydrolyzed to", "to mononucleotides", "mononucleotides by", "the rexo2", "rexo2 dimer", "bruni et", "szewczyk et", "al. 2020", "2020 .
              degradation", ".
              degradation of", "of mitochondrial", "mitochondrial rnas", "rnas is", "is regulated", "regulated by", "by rna", "rna binding", "binding proteins:", "proteins: fastk", "fastkd1 5", "and the", "the slirp:lrpprc", "slirp:lrpprc complex", "sasarman et", "chujo et", "ruzzenente et", "jourdain et", "al. 2017", "siira et", "in rackham", ". slirp:lrpprc", "slirp:lrpprc binds", "binds throughout", "throughout the", "mitochondrial transcriptome", "including 12s", "12s rrna", "16s rrna", "13 mrnas", "and acts", "acts to", "to stabilize", "stabilize rna", "rna structures", "inhibit hybridization", "hybridization of", "of complementary", "complementary rnas", "and extend", "extend the", "the half", "half lives", "lives of", "2017 .", ". fas", "fas activated", "activated serine/threonine", "serine/threonine kinase", "and its", "its homologs", "homologs fastkd1", "5 bind", "bind particular", "particular mitochondrial", "rnas and", "and affect", "affect their", "their stability", "stability and", "and processing", "in jourdain", "the human mitochondrial", "human mitochondrial genome", "mitochondrial genome encodes", "genome encodes two", "encodes two rrnas", "rrnas 22", "trnas and", "and 13 proteins.", "13 proteins. the", "proteins. the mitochondrial", "the mitochondrial genome", "mitochondrial genome is", "genome is transcribed", "is transcribed from", "transcribed from two", "from two divergent", "two divergent promoters", "divergent promoters into", "promoters into two", "into two large", "two large precursor", "large precursor rnas", "rnas one", "one from each", "from each strand", "strand that", "that are endonucleolytically", "are endonucleolytically processed", "endonucleolytically processed into", "processed into individual", "into individual mrnas", "mrnas trnas", "rrnas mercer", "mercer et al.", "et al. 2011", "2011 reviewed", "reviewed in barchiesi", "in barchiesi and", "barchiesi and vascotto", "and vascotto 2019", "2019 jedynak", "jedynak slyvka et", "slyvka et al.", "et al. 2021", "2021 rackham", "rackham and filipovska", "and filipovska 2022", "filipovska 2022 .", "2022 . heavy", ". heavy strand", "strand h", "strand dna", "dna is significantly", "is significantly more", "significantly more g", "more g rich", "g rich than", "rich than light", "than light strand", "strand l", "strand dna.", "dna. transcripts from", "transcripts from the", "from the h", "the h strand", "h strand encode", "strand encode eight", "encode eight monocistronic", "eight monocistronic mrnas", "mrnas two", "two bicistronic mrnas", "mt atp8/6 and", "atp8/6 and mt", "and mt nd4l/4", "and two rrnas.", "two rrnas. transcripts", "rrnas. transcripts from", "from the l\u2011strand", "the l\u2011strand encode", "l\u2011strand encode only", "encode only one", "only one mrna", "mrna mt\u2011nd6", "one long non", "long non coding", "non coding rna", "rna lncrna", "lncnd6 which", "which is antisense", "is antisense to", "antisense to mt", "to mt nd6", "nd6 and", "and eight trnas", "and two long", "two long non", "non coding rnas", "coding rnas designated", "rnas designated as", "designated as lncnd5", "lncnd5 and", "and lnccyt b", "lnccyt b rna", "b rna that", "rna that are", "that are antisense", "are antisense to", "antisense to the", "to the coding", "the coding mrnas", "coding mrnas mt", "mrnas mt nd5", "mt nd5 and", "nd5 and mt", "and mt cyb", "cyb cytb", "cytb mt", "rackham et al.", "al. 2011 .", "2011 . the", ". the l", "the l strand", "l strand and", "strand and h", "and h strand", "h strand transcripts", "strand transcripts are", "transcripts are complementary", "are complementary and", "and therefore", "therefore have", "have the potential", "the potential to", "potential to form", "to form large", "form large double", "large double stranded", "double stranded rnas", "rnas dsrnas", "yet very little", "very little dsrna", "little dsrna is", "dsrna is observed", "is observed in", "observed in wild", "in wild type", "wild type mitochondria.
              both", "type mitochondria.
              both dsrnas", "mitochondria.
              both dsrnas and", "dsrnas and normal", "and normal mrnas", "and rrnas are", "rrnas are hydrolyzed", "are hydrolyzed by", "hydrolyzed by the", "by the supv3l1:pnpt1", "the supv3l1:pnpt1 complex", "complex called", "called the degradosome", "degradosome which", "which is located", "is located mostly", "located mostly in", "mostly in mitochondrial", "in mitochondrial rna", "mitochondrial rna granules", "granules mrgs", "mrgs adjacent", "adjacent to the", "to the dna", "the dna containing", "dna containing nucleoid", "nucleoid reviewed", "reviewed in borowski", "in borowski et", "borowski et al.", "et al. 2010", "2010 rorbach", "rorbach and minczuk", "and minczuk 2012", "2012 kotrys", "kotrys and szczesny", "and szczesny 2019", "2019 rackham", "2022 . degradation", ". degradation appears", "degradation appears to", "appears to occur", "to occur in", "occur in subregions", "in subregions of", "subregions of mrgs", "of mrgs called", "mrgs called d", "called d foci", "foci borowski", "et al. 2013", "2013 van", "van haute et", "haute et al.", "et al. 2015", "al. 2015 .", "2015 . supv3l1", ". supv3l1 is", "supv3l1 is a", "is a helicase", "a helicase that", "helicase that unwinds", "that unwinds double", "unwinds double stranded", "double stranded rna", "rna shu", "shu et al.", "et al. 2004", "2004 wang", "wang et al.", "et al. 2009", "2009 dhir", "dhir et al.", "et al. 2018", "2018 jain", "jain et al.", "et al. 2022", "2022 to", "to provide single", "provide single stranded", "single stranded substrate", "stranded substrate to", "substrate to the", "to the pnpt1", "the pnpt1 exonuclease", "exonuclease wang", "2009 lin", "lin et al.", "et al. 2012", "al. 2012 .", "2012 . additionally", "additionally g", "g quadruplex structures", "quadruplex structures in", "structures in a", "in a subset", "a subset of", "subset of rnas", "of rnas are", "rnas are unwound", "are unwound by", "unwound by grsf1", "by grsf1 to", "grsf1 to provide", "to provide substrates", "provide substrates to", "substrates to the", "to the supv3l1:pnpt1", "complex antonicka", "antonicka et al.", "2013 pietras", "pietras et al.", "al. 2018 .", "2018 . however", "however other", "other rnas are", "rnas are stabilized", "are stabilized by", "stabilized by grsf1", "grsf1 antonicka", "al. 2013 .", "2013 . the", ". the pnpt1", "the pnpt1 3'", "pnpt1 3' 5'", "3' 5' exonuclease", "5' exonuclease hydrolyzes", "exonuclease hydrolyzes rnas", "hydrolyzes rnas to", "rnas to yield", "to yield 4", "yield 4 5", "4 5 nucleotide", "5 nucleotide \\nanornas\\", "nucleotide \\nanornas\\ which", "\\nanornas\\ which are", "which are further", "are further hydrolyzed", "further hydrolyzed to", "hydrolyzed to mononucleotides", "to mononucleotides by", "mononucleotides by the", "by the rexo2", "the rexo2 dimer", "dimer bruni", "bruni et al.", "2013 szewczyk", "szewczyk et al.", "et al. 2020", "al. 2020 .
              degradation", "2020 .
              degradation of", ".
              degradation of mitochondrial", "of mitochondrial rnas", "mitochondrial rnas is", "rnas is regulated", "is regulated by", "regulated by rna", "by rna binding", "rna binding proteins:", "binding proteins: fastk", "fastk fastkd1", "5 and", "and the slirp:lrpprc", "the slirp:lrpprc complex", "complex sasarman", "sasarman et al.", "2010 chujo", "chujo et al.", "2021 ruzzenente", "ruzzenente et al.", "2012 jourdain", "jourdain et al.", "et al. 2017", "2017 siira", "siira et al.", "2017 reviewed", "reviewed in rackham", "in rackham and", "2022 . slirp:lrpprc", ". slirp:lrpprc binds", "slirp:lrpprc binds throughout", "binds throughout the", "throughout the mitochondrial", "the mitochondrial transcriptome", "transcriptome including", "including 12s rrna", "rrna 16s", "rrna and", "and 13 mrnas", "mrnas and", "and acts to", "acts to stabilize", "to stabilize rna", "stabilize rna structures", "structures inhibit", "inhibit hybridization of", "hybridization of complementary", "of complementary rnas", "and extend the", "extend the half", "the half lives", "half lives of", "lives of rnas", "rnas sasarman", "2012 siira", "al. 2017 .", "2017 . fas", ". fas activated", "fas activated serine/threonine", "activated serine/threonine kinase", "kinase fastk", "fastk and", "and its homologs", "its homologs fastkd1", "homologs fastkd1 5", "fastkd1 5 bind", "5 bind particular", "bind particular mitochondrial", "particular mitochondrial rnas", "mitochondrial rnas and", "rnas and affect", "and affect their", "affect their stability", "their stability and", "stability and processing", "processing reviewed", "reviewed in jourdain", "in jourdain et", "2017 rackham", "the human mitochondrial genome", "human mitochondrial genome encodes", "mitochondrial genome encodes two", "genome encodes two rrnas", "two rrnas 22", "rrnas 22 trnas", "22 trnas and", "trnas and 13", "and 13 proteins. the", "13 proteins. the mitochondrial", "proteins. the mitochondrial genome", "the mitochondrial genome is", "mitochondrial genome is transcribed", "genome is transcribed from", "is transcribed from two", "transcribed from two divergent", "from two divergent promoters", "two divergent promoters into", "divergent promoters into two", "promoters into two large", "into two large precursor", "two large precursor rnas", "precursor rnas one", "rnas one from", "one from each strand", "each strand that", "strand that are", "that are endonucleolytically processed", "are endonucleolytically processed into", "endonucleolytically processed into individual", "processed into individual mrnas", "individual mrnas trnas", "trnas and rrnas", "and rrnas mercer", "rrnas mercer et", "mercer et al. 2011", "al. 2011 reviewed", "2011 reviewed in", "reviewed in barchiesi and", "in barchiesi and vascotto", "barchiesi and vascotto 2019", "vascotto 2019 jedynak", "2019 jedynak slyvka", "jedynak slyvka et al.", "slyvka et al. 2021", "al. 2021 rackham", "2021 rackham and", "rackham and filipovska 2022", "and filipovska 2022 .", "filipovska 2022 . heavy", "2022 . heavy strand", "heavy strand h", "strand h strand", "h strand dna", "strand dna is", "dna is significantly more", "is significantly more g", "significantly more g rich", "more g rich than", "g rich than light", "rich than light strand", "light strand l", "strand l strand", "l strand dna.", "strand dna. transcripts", "dna. transcripts from the", "transcripts from the h", "from the h strand", "the h strand encode", "h strand encode eight", "strand encode eight monocistronic", "encode eight monocistronic mrnas", "monocistronic mrnas two", "mrnas two bicistronic", "bicistronic mrnas mt", "mrnas mt atp8/6", "mt atp8/6 and mt", "atp8/6 and mt nd4l/4", "nd4l/4 14", "14 trnas and", "trnas and two", "and two rrnas. transcripts", "two rrnas. transcripts from", "rrnas. transcripts from the", "transcripts from the l\u2011strand", "from the l\u2011strand encode", "the l\u2011strand encode only", "l\u2011strand encode only one", "encode only one mrna", "one mrna mt\u2011nd6", "mt\u2011nd6 one", "one long non coding", "long non coding rna", "coding rna lncrna", "lncrna lncnd6", "lncnd6 which is", "which is antisense to", "is antisense to mt", "antisense to mt nd6", "mt nd6 and", "nd6 and eight", "eight trnas and", "and two long non", "two long non coding", "long non coding rnas", "non coding rnas designated", "coding rnas designated as", "rnas designated as lncnd5", "as lncnd5 and", "lncnd5 and lnccyt", "and lnccyt b rna", "lnccyt b rna that", "b rna that are", "rna that are antisense", "that are antisense to", "are antisense to the", "antisense to the coding", "to the coding mrnas", "the coding mrnas mt", "coding mrnas mt nd5", "mrnas mt nd5 and", "mt nd5 and mt", "nd5 and mt cyb", "mt cyb cytb", "cytb mt cytb", "cytb rackham", "rackham et al. 2011", "et al. 2011 .", "al. 2011 . the", "2011 . the l", ". the l strand", "the l strand and", "l strand and h", "strand and h strand", "and h strand transcripts", "h strand transcripts are", "strand transcripts are complementary", "transcripts are complementary and", "complementary and therefore", "therefore have the", "have the potential to", "the potential to form", "potential to form large", "to form large double", "form large double stranded", "large double stranded rnas", "stranded rnas dsrnas", "dsrnas yet", "yet very little dsrna", "very little dsrna is", "little dsrna is observed", "dsrna is observed in", "is observed in wild", "observed in wild type", "in wild type mitochondria.
              both", "wild type mitochondria.
              both dsrnas", "type mitochondria.
              both dsrnas and", "mitochondria.
              both dsrnas and normal", "dsrnas and normal mrnas", "normal mrnas trnas", "and rrnas are hydrolyzed", "rrnas are hydrolyzed by", "are hydrolyzed by the", "hydrolyzed by the supv3l1:pnpt1", "by the supv3l1:pnpt1 complex", "supv3l1:pnpt1 complex called", "complex called the", "the degradosome which", "degradosome which is", "which is located mostly", "is located mostly in", "located mostly in mitochondrial", "mostly in mitochondrial rna", "in mitochondrial rna granules", "rna granules mrgs", "mrgs adjacent to", "adjacent to the dna", "to the dna containing", "the dna containing nucleoid", "containing nucleoid reviewed", "nucleoid reviewed in", "reviewed in borowski et", "in borowski et al.", "borowski et al. 2010", "al. 2010 rorbach", "2010 rorbach and", "rorbach and minczuk 2012", "minczuk 2012 kotrys", "2012 kotrys and", "kotrys and szczesny 2019", "szczesny 2019 rackham", "2019 rackham and", "filipovska 2022 . degradation", "2022 . degradation appears", ". degradation appears to", "degradation appears to occur", "appears to occur in", "to occur in subregions", "occur in subregions of", "in subregions of mrgs", "subregions of mrgs called", "of mrgs called d", "mrgs called d foci", "d foci borowski", "foci borowski et", "borowski et al. 2013", "al. 2013 van", "2013 van haute", "van haute et al.", "haute et al. 2015", "et al. 2015 .", "al. 2015 . supv3l1", "2015 . supv3l1 is", ". supv3l1 is a", "supv3l1 is a helicase", "is a helicase that", "a helicase that unwinds", "helicase that unwinds double", "that unwinds double stranded", "unwinds double stranded rna", "stranded rna shu", "rna shu et", "shu et al. 2004", "al. 2004 wang", "2004 wang et", "wang et al. 2009", "al. 2009 dhir", "2009 dhir et", "dhir et al. 2018", "al. 2018 jain", "2018 jain et", "jain et al. 2022", "al. 2022 to", "2022 to provide", "to provide single stranded", "provide single stranded substrate", "single stranded substrate to", "stranded substrate to the", "substrate to the pnpt1", "to the pnpt1 exonuclease", "pnpt1 exonuclease wang", "exonuclease wang et", "al. 2009 lin", "2009 lin et", "lin et al. 2012", "et al. 2012 .", "al. 2012 . additionally", ". additionally g", "additionally g quadruplex", "g quadruplex structures in", "quadruplex structures in a", "structures in a subset", "in a subset of", "a subset of rnas", "subset of rnas are", "of rnas are unwound", "rnas are unwound by", "are unwound by grsf1", "unwound by grsf1 to", "by grsf1 to provide", "grsf1 to provide substrates", "to provide substrates to", "provide substrates to the", "substrates to the supv3l1:pnpt1", "to the supv3l1:pnpt1 complex", "supv3l1:pnpt1 complex antonicka", "complex antonicka et", "antonicka et al. 2013", "al. 2013 pietras", "2013 pietras et", "pietras et al. 2018", "et al. 2018 .", "al. 2018 . however", ". however other", "however other rnas", "other rnas are stabilized", "rnas are stabilized by", "are stabilized by grsf1", "by grsf1 antonicka", "grsf1 antonicka et", "et al. 2013 .", "al. 2013 . the", "2013 . the pnpt1", ". the pnpt1 3'", "the pnpt1 3' 5'", "pnpt1 3' 5' exonuclease", "3' 5' exonuclease hydrolyzes", "5' exonuclease hydrolyzes rnas", "exonuclease hydrolyzes rnas to", "hydrolyzes rnas to yield", "rnas to yield 4", "to yield 4 5", "yield 4 5 nucleotide", "4 5 nucleotide \\nanornas\\", "5 nucleotide \\nanornas\\ which", "nucleotide \\nanornas\\ which are", "\\nanornas\\ which are further", "which are further hydrolyzed", "are further hydrolyzed to", "further hydrolyzed to mononucleotides", "hydrolyzed to mononucleotides by", "to mononucleotides by the", "mononucleotides by the rexo2", "by the rexo2 dimer", "rexo2 dimer bruni", "dimer bruni et", "bruni et al. 2013", "al. 2013 szewczyk", "2013 szewczyk et", "szewczyk et al. 2020", "et al. 2020 .
              degradation", "al. 2020 .
              degradation of", "2020 .
              degradation of mitochondrial", ".
              degradation of mitochondrial rnas", "of mitochondrial rnas is", "mitochondrial rnas is regulated", "rnas is regulated by", "is regulated by rna", "regulated by rna binding", "by rna binding proteins:", "rna binding proteins: fastk", "proteins: fastk fastkd1", "fastk fastkd1 5", "fastkd1 5 and", "5 and the", "and the slirp:lrpprc complex", "slirp:lrpprc complex sasarman", "complex sasarman et", "sasarman et al. 2010", "al. 2010 chujo", "2010 chujo et", "chujo et al. 2021", "al. 2021 ruzzenente", "2021 ruzzenente et", "ruzzenente et al. 2012", "al. 2012 jourdain", "2012 jourdain et", "jourdain et al. 2017", "al. 2017 siira", "2017 siira et", "siira et al. 2017", "al. 2017 reviewed", "2017 reviewed in", "reviewed in rackham and", "in rackham and filipovska", "filipovska 2022 . slirp:lrpprc", "2022 . slirp:lrpprc binds", ". slirp:lrpprc binds throughout", "slirp:lrpprc binds throughout the", "binds throughout the mitochondrial", "throughout the mitochondrial transcriptome", "mitochondrial transcriptome including", "transcriptome including 12s", "12s rrna 16s", "rrna 16s rrna", "16s rrna and", "rrna and 13", "13 mrnas and", "mrnas and acts", "and acts to stabilize", "acts to stabilize rna", "to stabilize rna structures", "rna structures inhibit", "structures inhibit hybridization", "inhibit hybridization of complementary", "hybridization of complementary rnas", "complementary rnas and", "rnas and extend", "and extend the half", "extend the half lives", "the half lives of", "half lives of rnas", "of rnas sasarman", "rnas sasarman et", "chujo et al. 2012", "al. 2012 siira", "2012 siira et", "et al. 2017 .", "al. 2017 . fas", "2017 . fas activated", ". fas activated serine/threonine", "fas activated serine/threonine kinase", "serine/threonine kinase fastk", "fastk and its", "and its homologs fastkd1", "its homologs fastkd1 5", "homologs fastkd1 5 bind", "fastkd1 5 bind particular", "5 bind particular mitochondrial", "bind particular mitochondrial rnas", "particular mitochondrial rnas and", "mitochondrial rnas and affect", "rnas and affect their", "and affect their stability", "affect their stability and", "their stability and processing", "and processing reviewed", "processing reviewed in", "reviewed in jourdain et", "in jourdain et al.", "al. 2017 rackham", "2017 rackham and", "the human mitochondrial genome encodes", "human mitochondrial genome encodes two", "mitochondrial genome encodes two rrnas", "encodes two rrnas 22", "two rrnas 22 trnas", "22 trnas and 13", "trnas and 13 proteins.", "and 13 proteins. the mitochondrial", "13 proteins. the mitochondrial genome", "proteins. the mitochondrial genome is", "the mitochondrial genome is transcribed", "mitochondrial genome is transcribed from", "genome is transcribed from two", "is transcribed from two divergent", "transcribed from two divergent promoters", "from two divergent promoters into", "two divergent promoters into two", "divergent promoters into two large", "promoters into two large precursor", "into two large precursor rnas", "large precursor rnas one", "precursor rnas one from", "rnas one from each", "from each strand that", "each strand that are", "strand that are endonucleolytically", "that are endonucleolytically processed into", "are endonucleolytically processed into individual", "endonucleolytically processed into individual mrnas", "into individual mrnas trnas", "mrnas trnas and", "and rrnas mercer et", "rrnas mercer et al.", "et al. 2011 reviewed", "al. 2011 reviewed in", "2011 reviewed in barchiesi", "reviewed in barchiesi and vascotto", "in barchiesi and vascotto 2019", "and vascotto 2019 jedynak", "vascotto 2019 jedynak slyvka", "2019 jedynak slyvka et", "jedynak slyvka et al. 2021", "et al. 2021 rackham", "al. 2021 rackham and", "2021 rackham and filipovska", "rackham and filipovska 2022 .", "and filipovska 2022 . heavy", "filipovska 2022 . heavy strand", ". heavy strand h", "heavy strand h strand", "h strand dna is", "strand dna is significantly", "dna is significantly more g", "is significantly more g rich", "significantly more g rich than", "more g rich than light", "g rich than light strand", "than light strand l", "light strand l strand", "l strand dna. transcripts", "strand dna. transcripts from", "dna. transcripts from the h", "transcripts from the h strand", "from the h strand encode", "the h strand encode eight", "h strand encode eight monocistronic", "strand encode eight monocistronic mrnas", "eight monocistronic mrnas two", "monocistronic mrnas two bicistronic", "mrnas two bicistronic mrnas", "two bicistronic mrnas mt", "bicistronic mrnas mt atp8/6", "mrnas mt atp8/6 and", "mt atp8/6 and mt nd4l/4", "mt nd4l/4 14", "nd4l/4 14 trnas", "14 trnas and two", "trnas and two rrnas.", "and two rrnas. transcripts from", "two rrnas. transcripts from the", "rrnas. transcripts from the l\u2011strand", "transcripts from the l\u2011strand encode", "from the l\u2011strand encode only", "the l\u2011strand encode only one", "l\u2011strand encode only one mrna", "only one mrna mt\u2011nd6", "mt\u2011nd6 one long", "one long non coding rna", "non coding rna lncrna", "lncnd6 which is antisense", "which is antisense to mt", "is antisense to mt nd6", "to mt nd6 and", "mt nd6 and eight", "nd6 and eight trnas", "and eight trnas and", "eight trnas and two", "trnas and two long", "and two long non coding", "two long non coding rnas", "long non coding rnas designated", "non coding rnas designated as", "coding rnas designated as lncnd5", "designated as lncnd5 and", "as lncnd5 and lnccyt", "lncnd5 and lnccyt b", "and lnccyt b rna that", "lnccyt b rna that are", "b rna that are antisense", "rna that are antisense to", "that are antisense to the", "are antisense to the coding", "antisense to the coding mrnas", "to the coding mrnas mt", "the coding mrnas mt nd5", "coding mrnas mt nd5 and", "mrnas mt nd5 and mt", "mt nd5 and mt cyb", "and mt cyb cytb", "cyb cytb mt", "mt cytb rackham", "cytb rackham et", "rackham et al. 2011 .", "et al. 2011 . the", "al. 2011 . the l", "2011 . the l strand", ". the l strand and", "the l strand and h", "l strand and h strand", "strand and h strand transcripts", "and h strand transcripts are", "h strand transcripts are complementary", "strand transcripts are complementary and", "are complementary and therefore", "and therefore have", "therefore have the potential", "have the potential to form", "the potential to form large", "potential to form large double", "to form large double stranded", "form large double stranded rnas", "double stranded rnas dsrnas", "dsrnas yet very", "yet very little dsrna is", "very little dsrna is observed", "little dsrna is observed in", "dsrna is observed in wild", "is observed in wild type", "observed in wild type mitochondria.
              both", "in wild type mitochondria.
              both dsrnas", "wild type mitochondria.
              both dsrnas and", "type mitochondria.
              both dsrnas and normal", "mitochondria.
              both dsrnas and normal mrnas", "and normal mrnas trnas", "trnas and rrnas are", "and rrnas are hydrolyzed by", "rrnas are hydrolyzed by the", "are hydrolyzed by the supv3l1:pnpt1", "hydrolyzed by the supv3l1:pnpt1 complex", "the supv3l1:pnpt1 complex called", "supv3l1:pnpt1 complex called the", "complex called the degradosome", "called the degradosome which", "the degradosome which is", "degradosome which is located", "which is located mostly in", "is located mostly in mitochondrial", "located mostly in mitochondrial rna", "mostly in mitochondrial rna granules", "mitochondrial rna granules mrgs", "granules mrgs adjacent", "mrgs adjacent to the", "adjacent to the dna containing", "to the dna containing nucleoid", "dna containing nucleoid reviewed", "containing nucleoid reviewed in", "nucleoid reviewed in borowski", "reviewed in borowski et al.", "in borowski et al. 2010", "et al. 2010 rorbach", "al. 2010 rorbach and", "2010 rorbach and minczuk", "and minczuk 2012 kotrys", "minczuk 2012 kotrys and", "2012 kotrys and szczesny", "and szczesny 2019 rackham", "szczesny 2019 rackham and", "2019 rackham and filipovska", "and filipovska 2022 . degradation", "filipovska 2022 . degradation appears", "2022 . degradation appears to", ". degradation appears to occur", "degradation appears to occur in", "appears to occur in subregions", "to occur in subregions of", "occur in subregions of mrgs", "in subregions of mrgs called", "subregions of mrgs called d", "of mrgs called d foci", "called d foci borowski", "d foci borowski et", "foci borowski et al.", "et al. 2013 van", "al. 2013 van haute", "2013 van haute et", "van haute et al. 2015", "haute et al. 2015 .", "et al. 2015 . supv3l1", "al. 2015 . supv3l1 is", "2015 . supv3l1 is a", ". supv3l1 is a helicase", "supv3l1 is a helicase that", "is a helicase that unwinds", "a helicase that unwinds double", "helicase that unwinds double stranded", "that unwinds double stranded rna", "double stranded rna shu", "stranded rna shu et", "rna shu et al.", "et al. 2004 wang", "al. 2004 wang et", "2004 wang et al.", "et al. 2009 dhir", "al. 2009 dhir et", "2009 dhir et al.", "et al. 2018 jain", "al. 2018 jain et", "2018 jain et al.", "et al. 2022 to", "al. 2022 to provide", "2022 to provide single", "to provide single stranded substrate", "provide single stranded substrate to", "single stranded substrate to the", "stranded substrate to the pnpt1", "substrate to the pnpt1 exonuclease", "the pnpt1 exonuclease wang", "pnpt1 exonuclease wang et", "exonuclease wang et al.", "et al. 2009 lin", "al. 2009 lin et", "2009 lin et al.", "lin et al. 2012 .", "et al. 2012 . additionally", "2012 . additionally g", ". additionally g quadruplex", "additionally g quadruplex structures", "g quadruplex structures in a", "quadruplex structures in a subset", "structures in a subset of", "in a subset of rnas", "a subset of rnas are", "subset of rnas are unwound", "of rnas are unwound by", "rnas are unwound by grsf1", "are unwound by grsf1 to", "unwound by grsf1 to provide", "by grsf1 to provide substrates", "grsf1 to provide substrates to", "to provide substrates to the", "provide substrates to the supv3l1:pnpt1", "substrates to the supv3l1:pnpt1 complex", "the supv3l1:pnpt1 complex antonicka", "supv3l1:pnpt1 complex antonicka et", "complex antonicka et al.", "et al. 2013 pietras", "al. 2013 pietras et", "2013 pietras et al.", "pietras et al. 2018 .", "et al. 2018 . however", "2018 . however other", ". however other rnas", "however other rnas are", "other rnas are stabilized by", "rnas are stabilized by grsf1", "stabilized by grsf1 antonicka", "by grsf1 antonicka et", "grsf1 antonicka et al.", "antonicka et al. 2013 .", "et al. 2013 . the", "al. 2013 . the pnpt1", "2013 . the pnpt1 3'", ". the pnpt1 3' 5'", "the pnpt1 3' 5' exonuclease", "pnpt1 3' 5' exonuclease hydrolyzes", "3' 5' exonuclease hydrolyzes rnas", "5' exonuclease hydrolyzes rnas to", "exonuclease hydrolyzes rnas to yield", "hydrolyzes rnas to yield 4", "rnas to yield 4 5", "to yield 4 5 nucleotide", "yield 4 5 nucleotide \\nanornas\\", "4 5 nucleotide \\nanornas\\ which", "5 nucleotide \\nanornas\\ which are", "nucleotide \\nanornas\\ which are further", "\\nanornas\\ which are further hydrolyzed", "which are further hydrolyzed to", "are further hydrolyzed to mononucleotides", "further hydrolyzed to mononucleotides by", "hydrolyzed to mononucleotides by the", "to mononucleotides by the rexo2", "mononucleotides by the rexo2 dimer", "the rexo2 dimer bruni", "rexo2 dimer bruni et", "dimer bruni et al.", "et al. 2013 szewczyk", "al. 2013 szewczyk et", "2013 szewczyk et al.", "szewczyk et al. 2020 .
              degradation", "et al. 2020 .
              degradation of", "al. 2020 .
              degradation of mitochondrial", "2020 .
              degradation of mitochondrial rnas", ".
              degradation of mitochondrial rnas is", "of mitochondrial rnas is regulated", "mitochondrial rnas is regulated by", "rnas is regulated by rna", "is regulated by rna binding", "regulated by rna binding proteins:", "by rna binding proteins: fastk", "binding proteins: fastk fastkd1", "proteins: fastk fastkd1 5", "fastkd1 5 and the", "5 and the slirp:lrpprc", "the slirp:lrpprc complex sasarman", "slirp:lrpprc complex sasarman et", "complex sasarman et al.", "et al. 2010 chujo", "al. 2010 chujo et", "2010 chujo et al.", "et al. 2021 ruzzenente", "al. 2021 ruzzenente et", "2021 ruzzenente et al.", "et al. 2012 jourdain", "al. 2012 jourdain et", "2012 jourdain et al.", "et al. 2017 siira", "al. 2017 siira et", "2017 siira et al.", "et al. 2017 reviewed", "al. 2017 reviewed in", "2017 reviewed in rackham", "reviewed in rackham and filipovska", "in rackham and filipovska 2022", "and filipovska 2022 . slirp:lrpprc", "filipovska 2022 . slirp:lrpprc binds", "2022 . slirp:lrpprc binds throughout", ". slirp:lrpprc binds throughout the", "slirp:lrpprc binds throughout the mitochondrial", "binds throughout the mitochondrial transcriptome", "the mitochondrial transcriptome including", "mitochondrial transcriptome including 12s", "transcriptome including 12s rrna", "including 12s rrna 16s", "12s rrna 16s rrna", "16s rrna and 13", "rrna and 13 mrnas", "and 13 mrnas and", "13 mrnas and acts", "mrnas and acts to", "and acts to stabilize rna", "acts to stabilize rna structures", "stabilize rna structures inhibit", "rna structures inhibit hybridization", "structures inhibit hybridization of", "inhibit hybridization of complementary rnas", "of complementary rnas and", "complementary rnas and extend", "rnas and extend the", "and extend the half lives", "extend the half lives of", "the half lives of rnas", "lives of rnas sasarman", "of rnas sasarman et", "rnas sasarman et al.", "et al. 2012 siira", "al. 2012 siira et", "2012 siira et al.", "siira et al. 2017 .", "et al. 2017 . fas", "al. 2017 . fas activated", "2017 . fas activated serine/threonine", ". fas activated serine/threonine kinase", "activated serine/threonine kinase fastk", "kinase fastk and", "fastk and its homologs", "and its homologs fastkd1 5", "its homologs fastkd1 5 bind", "homologs fastkd1 5 bind particular", "fastkd1 5 bind particular mitochondrial", "5 bind particular mitochondrial rnas", "bind particular mitochondrial rnas and", "particular mitochondrial rnas and affect", "mitochondrial rnas and affect their", "rnas and affect their stability", "and affect their stability and", "affect their stability and processing", "stability and processing reviewed", "and processing reviewed in", "processing reviewed in jourdain", "reviewed in jourdain et al.", "in jourdain et al. 2017", "et al. 2017 rackham", "al. 2017 rackham and", "2017 rackham and filipovska" ] }, { "record_id": "GLY_000594_1_2100", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9837092", "r hsa", "hsa 9837092", "r hsa 9837092" ] }, { "record_id": "GLY_000594_1_2100", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "fastk family", "family proteins", "proteins regulate", "regulate processing", "processing and", "and stability", "stability of", "of mitochondrial", "mitochondrial rnas", "fastk family proteins", "family proteins regulate", "proteins regulate processing", "regulate processing and", "processing and stability", "and stability of", "stability of mitochondrial", "of mitochondrial rnas", "fastk family proteins regulate", "family proteins regulate processing", "proteins regulate processing and", "regulate processing and stability", "processing and stability of", "and stability of mitochondrial", "stability of mitochondrial rnas", "fastk family proteins regulate processing", "family proteins regulate processing and", "proteins regulate processing and stability", "regulate processing and stability of", "processing and stability of mitochondrial", "and stability of mitochondrial rnas", "fas activated", "activated serine/threonine", "serine/threonine kinase", "and its", "its homologs", "homologs fastkd1", "fastkd1 5", "5 each", "each contain", "contain three", "three conserved", "conserved domains", "and rap", "that bind", "bind rna", "castello et", "et al.", "al. 2012", "baltz et", "2012 .", ". fastkd1", "5 and", "and the", "the short", "short isoform", "isoform of", "of fastk", "fastk localize", "localize to", "to mitochondria", "mitochondria where", "where they", "they participate", "participate in", "in regulating", "regulating the", "the processing", "of rna", "simarro et", "al. 2010", "reviewed in", "in jourdain", "jourdain et", "al. 2017", "2017 .
              fastk", ".
              fastk interacts", "interacts with", "with the", "the 3'", "3' end", "end of", "of the", "the mt", "mt nd6", "nd6 mrna", "mrna and", "and protects", "protects the", "the mrna", "mrna from", "from degradation", "degradation by", "by the", "the degradosome", "al. 2015", "2015 .", ". the", "mrna is", "is unusual", "unusual in", "in being", "being processed", "processed from", "from the", "the large", "large l", "l strand", "strand precursor", "precursor without", "without flanking", "flanking trna", "trna genes", "genes and", "and thus", "thus without", "without canonical", "canonical processing", "processing by", "by rnase", "rnase p", "p and", "and rnase", "rnase z.", "z. fastk", "fastk may", "in an", "an uncharacterized", "uncharacterized non", "non canonical", "canonical mechanism", "mechanism of", "rna processing", "processing or", "or protect", "protect 3'", "3' ends", "ends produced", "produced by", "by such", "such a", "a mechanism.
              fastkd1", "mechanism.
              fastkd1 acts", "acts to", "to reduce", "reduce the", "the abundance", "abundance of", "mt nd3", "nd3 mrna", "mrna by", "by an", "uncharacterized mechanism", "boehm et", "2017 .
              fastkd2", ".
              fastkd2 binds", "binds the", "the 16s", "16s rrna", "rrna and", "and participates", "participates in", "in their", "their processing", "and expression", "antonicka and", "and shoubridge", "shoubridge 2015", "popow et", ". fastkd2", "fastkd2 interacts", "with several", "several mitochondrial", "mitochondrial proteins", "proteins including", "including mterfd1", "and ngrn", "antonicka et", "2017 .", ".
              fastkd3", "
              fastkd3 increases", "increases levels", "levels of", "of five", "five mitochondrial", "mitochondrial mrnas", "mt nd2", "mt cyb", "mt co2", "mt atp8/6", "atp8/6 bicistronic", "bicistronic mrna", "and increases", "increases translation", "translation of", "of mt", "mt co1", "co1 mrna", "mrna through", "through uncharacterized", "uncharacterized mechanisms", "al. 2016", "ohkubo et", "al. 2021", "2021 .
              tbrg4", "binds most", "most rnas", "rnas transcribed", "transcribed from", "the h", "h strand", "strand and", "and enhances", "enhances the", "the expression", "expression levels", "mt co3", "and mt", "mt nd5", "nd5 mrnas", "wolf and", "and mootha", "mootha 2014", "2021 .", ". tbrg4", "tbrg4 stabilizes", "stabilizes mt", "co2 mrnas", "mrnas and", "and assists", "assists the", "processing of", "nd5 and", "cyb mrnas", "2021 .
              fastkd5", ".
              fastkd5 binds", "binds 12s", "12s rrna", "and all", "all mrnas", "mrnas except", "except mt", "nd3 and", "and reduces", "reduces levels", ". .", "fas activated serine/threonine", "activated serine/threonine kinase", "kinase fastk", "fastk and", "and its homologs", "its homologs fastkd1", "homologs fastkd1 5", "fastkd1 5 each", "5 each contain", "each contain three", "contain three conserved", "three conserved domains", "domains fast_1", "fast_1 fast_2", "fast_2 and", "rap that", "that bind rna", "rna castello", "castello et al.", "et al. 2012", "2012 baltz", "baltz et al.", "al. 2012 .", "2012 . fastkd1", ". fastkd1 5", "fastkd1 5 and", "5 and the", "and the short", "the short isoform", "short isoform of", "isoform of fastk", "of fastk localize", "fastk localize to", "localize to mitochondria", "to mitochondria where", "mitochondria where they", "where they participate", "they participate in", "participate in regulating", "in regulating the", "regulating the processing", "the processing and", "stability of rna", "rna simarro", "simarro et al.", "et al. 2010", "2010 reviewed", "reviewed in jourdain", "in jourdain et", "jourdain et al.", "et al. 2017", "al. 2017 .
              fastk", "2017 .
              fastk interacts", ".
              fastk interacts with", "interacts with the", "with the 3'", "the 3' end", "3' end of", "end of the", "of the mt", "the mt nd6", "mt nd6 mrna", "nd6 mrna and", "mrna and protects", "and protects the", "protects the mrna", "the mrna from", "mrna from degradation", "from degradation by", "degradation by the", "by the degradosome", "degradosome supv3l1:pnpt1", "supv3l1:pnpt1 jourdain", "et al. 2015", "al. 2015 .", "2015 . the", ". the mt", "nd6 mrna is", "mrna is unusual", "is unusual in", "unusual in being", "in being processed", "being processed from", "processed from the", "from the large", "the large l", "large l strand", "l strand precursor", "strand precursor without", "precursor without flanking", "without flanking trna", "flanking trna genes", "trna genes and", "genes and thus", "and thus without", "thus without canonical", "without canonical processing", "canonical processing by", "processing by rnase", "by rnase p", "rnase p and", "p and rnase", "and rnase z.", "rnase z. fastk", "z. fastk may", "may therefore", "therefore participate", "participate in an", "in an uncharacterized", "an uncharacterized non", "uncharacterized non canonical", "non canonical mechanism", "canonical mechanism of", "mechanism of rna", "of rna processing", "rna processing or", "processing or protect", "or protect 3'", "protect 3' ends", "3' ends produced", "ends produced by", "produced by such", "by such a", "such a mechanism.
              fastkd1", "a mechanism.
              fastkd1 acts", "mechanism.
              fastkd1 acts to", "acts to reduce", "to reduce the", "reduce the abundance", "the abundance of", "abundance of the", "the mt nd3", "mt nd3 mrna", "nd3 mrna by", "mrna by an", "by an uncharacterized", "an uncharacterized mechanism", "mechanism boehm", "boehm et al.", "al. 2017 .
              fastkd2", "2017 .
              fastkd2 binds", ".
              fastkd2 binds the", "binds the 16s", "the 16s rrna", "16s rrna and", "rrna and the", "and the mt", "mrna and participates", "and participates in", "participates in their", "in their processing", "their processing and", "processing and expression", "expression antonicka", "antonicka and shoubridge", "and shoubridge 2015", "2015 popow", "popow et al.", "2015 . fastkd2", ". fastkd2 interacts", "fastkd2 interacts with", "interacts with several", "with several mitochondrial", "several mitochondrial proteins", "mitochondrial proteins including", "proteins including mterfd1", "mterfd1 trub2", "trub2 wbscr16", "wbscr16 and", "ngrn antonicka", "antonicka et al.", "al. 2017 .", "2017 .
              fastkd3", ".
              fastkd3 increases", "
              fastkd3 increases levels", "increases levels of", "levels of five", "of five mitochondrial", "five mitochondrial mrnas", "mrnas mt", "nd2 mt", "nd3 mt", "cyb mt", "co2 and", "the mt atp8/6", "mt atp8/6 bicistronic", "atp8/6 bicistronic mrna", "and increases translation", "increases translation of", "translation of mt", "of mt co1", "mt co1 mrna", "co1 mrna through", "mrna through uncharacterized", "through uncharacterized mechanisms", "mechanisms boehm", "et al. 2016", "2016 ohkubo", "ohkubo et al.", "et al. 2021", "al. 2021 .
              tbrg4", ".
              tbrg4 fastkd4", "fastkd4 binds", "binds most rnas", "most rnas transcribed", "rnas transcribed from", "transcribed from the", "from the h", "the h strand", "h strand and", "strand and enhances", "and enhances the", "enhances the expression", "the expression levels", "expression levels of", "levels of mt", "of mt atp8/6", "atp8/6 mt", "co1 mt", "co2 mt", "co3 mt", "cyb and", "and mt nd5", "mt nd5 mrnas", "mrnas wolf", "wolf and mootha", "and mootha 2014", "2014 boehm", "2017 ohkubo", "al. 2021 .", "2021 . tbrg4", ". tbrg4 stabilizes", "tbrg4 stabilizes mt", "stabilizes mt co1", "and mt co2", "mt co2 mrnas", "co2 mrnas and", "mrnas and assists", "and assists the", "assists the processing", "the processing of", "processing of mt", "of mt nd5", "mt nd5 and", "nd5 and mt", "and mt cyb", "mt cyb mrnas", "mrnas boehm", "al. 2021 .
              fastkd5", "2021 .
              fastkd5 binds", ".
              fastkd5 binds 12s", "binds 12s rrna", "12s rrna and", "rrna and all", "and all mrnas", "all mrnas except", "mrnas except mt", "except mt nd3", "mt nd3 and", "nd3 and reduces", "and reduces levels", "reduces levels of", "mrnas antonicka", "2015 ohkubo", "2021 . .", "fas activated serine/threonine kinase", "serine/threonine kinase fastk", "fastk and its", "and its homologs fastkd1", "its homologs fastkd1 5", "homologs fastkd1 5 each", "fastkd1 5 each contain", "5 each contain three", "each contain three conserved", "contain three conserved domains", "conserved domains fast_1", "fast_2 and rap", "and rap that", "rap that bind", "bind rna castello", "rna castello et", "castello et al. 2012", "al. 2012 baltz", "2012 baltz et", "baltz et al. 2012", "et al. 2012 .", "al. 2012 . fastkd1", "2012 . fastkd1 5", ". fastkd1 5 and", "fastkd1 5 and the", "5 and the short", "and the short isoform", "the short isoform of", "short isoform of fastk", "isoform of fastk localize", "of fastk localize to", "fastk localize to mitochondria", "localize to mitochondria where", "to mitochondria where they", "mitochondria where they participate", "where they participate in", "they participate in regulating", "participate in regulating the", "in regulating the processing", "regulating the processing and", "the processing and stability", "and stability of rna", "of rna simarro", "rna simarro et", "simarro et al. 2010", "al. 2010 reviewed", "2010 reviewed in", "reviewed in jourdain et", "in jourdain et al.", "jourdain et al. 2017", "et al. 2017 .
              fastk", "al. 2017 .
              fastk interacts", "2017 .
              fastk interacts with", ".
              fastk interacts with the", "interacts with the 3'", "with the 3' end", "the 3' end of", "3' end of the", "end of the mt", "of the mt nd6", "the mt nd6 mrna", "mt nd6 mrna and", "nd6 mrna and protects", "mrna and protects the", "and protects the mrna", "protects the mrna from", "the mrna from degradation", "mrna from degradation by", "from degradation by the", "degradation by the degradosome", "the degradosome supv3l1:pnpt1", "supv3l1:pnpt1 jourdain et", "jourdain et al. 2015", "et al. 2015 .", "al. 2015 . the", "2015 . the mt", ". the mt nd6", "mt nd6 mrna is", "nd6 mrna is unusual", "mrna is unusual in", "is unusual in being", "unusual in being processed", "in being processed from", "being processed from the", "processed from the large", "from the large l", "the large l strand", "large l strand precursor", "l strand precursor without", "strand precursor without flanking", "precursor without flanking trna", "without flanking trna genes", "flanking trna genes and", "trna genes and thus", "genes and thus without", "and thus without canonical", "thus without canonical processing", "without canonical processing by", "canonical processing by rnase", "processing by rnase p", "by rnase p and", "rnase p and rnase", "p and rnase z.", "and rnase z. fastk", "rnase z. fastk may", "fastk may therefore", "therefore participate in", "participate in an uncharacterized", "in an uncharacterized non", "an uncharacterized non canonical", "uncharacterized non canonical mechanism", "non canonical mechanism of", "canonical mechanism of rna", "mechanism of rna processing", "of rna processing or", "rna processing or protect", "processing or protect 3'", "or protect 3' ends", "protect 3' ends produced", "3' ends produced by", "ends produced by such", "produced by such a", "by such a mechanism.
              fastkd1", "such a mechanism.
              fastkd1 acts", "a mechanism.
              fastkd1 acts to", "mechanism.
              fastkd1 acts to reduce", "acts to reduce the", "to reduce the abundance", "reduce the abundance of", "the abundance of the", "abundance of the mt", "of the mt nd3", "the mt nd3 mrna", "mt nd3 mrna by", "nd3 mrna by an", "mrna by an uncharacterized", "by an uncharacterized mechanism", "uncharacterized mechanism boehm", "mechanism boehm et", "boehm et al. 2017", "et al. 2017 .
              fastkd2", "al. 2017 .
              fastkd2 binds", "2017 .
              fastkd2 binds the", ".
              fastkd2 binds the 16s", "binds the 16s rrna", "the 16s rrna and", "16s rrna and the", "rrna and the mt", "and the mt nd6", "nd6 mrna and participates", "mrna and participates in", "and participates in their", "participates in their processing", "in their processing and", "their processing and expression", "and expression antonicka", "expression antonicka and", "antonicka and shoubridge 2015", "shoubridge 2015 popow", "2015 popow et", "popow et al. 2015", "al. 2015 . fastkd2", "2015 . fastkd2 interacts", ". fastkd2 interacts with", "fastkd2 interacts with several", "interacts with several mitochondrial", "with several mitochondrial proteins", "several mitochondrial proteins including", "mitochondrial proteins including mterfd1", "including mterfd1 trub2", "wbscr16 and ngrn", "and ngrn antonicka", "ngrn antonicka et", "antonicka et al. 2017", "et al. 2017 .", "al. 2017 .
              fastkd3", "2017 .
              fastkd3 increases", ".
              fastkd3 increases levels", "
              fastkd3 increases levels of", "increases levels of five", "levels of five mitochondrial", "of five mitochondrial mrnas", "mitochondrial mrnas mt", "mrnas mt nd2", "mt nd2 mt", "nd2 mt nd3", "mt nd3 mt", "nd3 mt cyb", "mt cyb mt", "cyb mt co2", "mt co2 and", "co2 and the", "and the mt atp8/6", "the mt atp8/6 bicistronic", "mt atp8/6 bicistronic mrna", "bicistronic mrna and", "mrna and increases", "and increases translation of", "increases translation of mt", "translation of mt co1", "of mt co1 mrna", "mt co1 mrna through", "co1 mrna through uncharacterized", "mrna through uncharacterized mechanisms", "uncharacterized mechanisms boehm", "mechanisms boehm et", "boehm et al. 2016", "al. 2016 ohkubo", "2016 ohkubo et", "ohkubo et al. 2021", "et al. 2021 .
              tbrg4", "2021 .
              tbrg4 fastkd4", "fastkd4 binds most", "binds most rnas transcribed", "most rnas transcribed from", "rnas transcribed from the", "transcribed from the h", "from the h strand", "the h strand and", "h strand and enhances", "strand and enhances the", "and enhances the expression", "enhances the expression levels", "the expression levels of", "expression levels of mt", "levels of mt atp8/6", "mt atp8/6 mt", "atp8/6 mt co1", "mt co1 mt", "co1 mt co2", "mt co2 mt", "co2 mt co3", "mt co3 mt", "co3 mt nd3", "mt cyb and", "cyb and mt", "and mt nd5 mrnas", "nd5 mrnas wolf", "mrnas wolf and", "wolf and mootha 2014", "mootha 2014 boehm", "2014 boehm et", "al. 2017 ohkubo", "2017 ohkubo et", "et al. 2021 .", "al. 2021 . tbrg4", "2021 . tbrg4 stabilizes", ". tbrg4 stabilizes mt", "tbrg4 stabilizes mt co1", "co1 mt nd3", "nd3 and mt", "and mt co2 mrnas", "mt co2 mrnas and", "co2 mrnas and assists", "mrnas and assists the", "and assists the processing", "assists the processing of", "the processing of mt", "processing of mt nd5", "of mt nd5 and", "mt nd5 and mt", "nd5 and mt cyb", "and mt cyb mrnas", "cyb mrnas boehm", "mrnas boehm et", "et al. 2021 .
              fastkd5", "al. 2021 .
              fastkd5 binds", "2021 .
              fastkd5 binds 12s", ".
              fastkd5 binds 12s rrna", "binds 12s rrna and", "12s rrna and all", "rrna and all mrnas", "and all mrnas except", "all mrnas except mt", "mrnas except mt nd3", "except mt nd3 and", "mt nd3 and reduces", "nd3 and reduces levels", "and reduces levels of", "reduces levels of mt", "co1 mt co3", "co3 mt nd5", "cyb mrnas antonicka", "mrnas antonicka and", "shoubridge 2015 ohkubo", "2015 ohkubo et", "al. 2021 . .", "activated serine/threonine kinase fastk", "kinase fastk and", "fastk and its homologs", "and its homologs fastkd1 5", "its homologs fastkd1 5 each", "homologs fastkd1 5 each contain", "fastkd1 5 each contain three", "5 each contain three conserved", "each contain three conserved domains", "three conserved domains fast_1", "domains fast_1 fast_2", "fast_1 fast_2 and", "and rap that bind", "rap that bind rna", "that bind rna castello", "bind rna castello et", "rna castello et al.", "et al. 2012 baltz", "al. 2012 baltz et", "2012 baltz et al.", "baltz et al. 2012 .", "et al. 2012 . fastkd1", "al. 2012 . fastkd1 5", "2012 . fastkd1 5 and", ". fastkd1 5 and the", "fastkd1 5 and the short", "5 and the short isoform", "and the short isoform of", "the short isoform of fastk", "short isoform of fastk localize", "isoform of fastk localize to", "of fastk localize to mitochondria", "fastk localize to mitochondria where", "localize to mitochondria where they", "to mitochondria where they participate", "mitochondria where they participate in", "where they participate in regulating", "they participate in regulating the", "participate in regulating the processing", "in regulating the processing and", "regulating the processing and stability", "the processing and stability of", "processing and stability of rna", "stability of rna simarro", "of rna simarro et", "rna simarro et al.", "et al. 2010 reviewed", "al. 2010 reviewed in", "2010 reviewed in jourdain", "reviewed in jourdain et al.", "in jourdain et al. 2017", "jourdain et al. 2017 .
              fastk", "et al. 2017 .
              fastk interacts", "al. 2017 .
              fastk interacts with", "2017 .
              fastk interacts with the", ".
              fastk interacts with the 3'", "interacts with the 3' end", "with the 3' end of", "the 3' end of the", "3' end of the mt", "end of the mt nd6", "of the mt nd6 mrna", "the mt nd6 mrna and", "mt nd6 mrna and protects", "nd6 mrna and protects the", "mrna and protects the mrna", "and protects the mrna from", "protects the mrna from degradation", "the mrna from degradation by", "mrna from degradation by the", "from degradation by the degradosome", "by the degradosome supv3l1:pnpt1", "degradosome supv3l1:pnpt1 jourdain", "supv3l1:pnpt1 jourdain et al.", "jourdain et al. 2015 .", "et al. 2015 . the", "al. 2015 . the mt", "2015 . the mt nd6", ". the mt nd6 mrna", "the mt nd6 mrna is", "mt nd6 mrna is unusual", "nd6 mrna is unusual in", "mrna is unusual in being", "is unusual in being processed", "unusual in being processed from", "in being processed from the", "being processed from the large", "processed from the large l", "from the large l strand", "the large l strand precursor", "large l strand precursor without", "l strand precursor without flanking", "strand precursor without flanking trna", "precursor without flanking trna genes", "without flanking trna genes and", "flanking trna genes and thus", "trna genes and thus without", "genes and thus without canonical", "and thus without canonical processing", "thus without canonical processing by", "without canonical processing by rnase", "canonical processing by rnase p", "processing by rnase p and", "by rnase p and rnase", "rnase p and rnase z.", "p and rnase z. fastk", "and rnase z. fastk may", "z. fastk may therefore", "may therefore participate", "therefore participate in an", "participate in an uncharacterized non", "in an uncharacterized non canonical", "an uncharacterized non canonical mechanism", "uncharacterized non canonical mechanism of", "non canonical mechanism of rna", "canonical mechanism of rna processing", "mechanism of rna processing or", "of rna processing or protect", "rna processing or protect 3'", "processing or protect 3' ends", "or protect 3' ends produced", "protect 3' ends produced by", "3' ends produced by such", "ends produced by such a", "produced by such a mechanism.
              fastkd1", "by such a mechanism.
              fastkd1 acts", "such a mechanism.
              fastkd1 acts to", "a mechanism.
              fastkd1 acts to reduce", "mechanism.
              fastkd1 acts to reduce the", "acts to reduce the abundance", "to reduce the abundance of", "reduce the abundance of the", "the abundance of the mt", "abundance of the mt nd3", "of the mt nd3 mrna", "the mt nd3 mrna by", "mt nd3 mrna by an", "nd3 mrna by an uncharacterized", "mrna by an uncharacterized mechanism", "an uncharacterized mechanism boehm", "uncharacterized mechanism boehm et", "mechanism boehm et al.", "boehm et al. 2017 .
              fastkd2", "et al. 2017 .
              fastkd2 binds", "al. 2017 .
              fastkd2 binds the", "2017 .
              fastkd2 binds the 16s", ".
              fastkd2 binds the 16s rrna", "binds the 16s rrna and", "the 16s rrna and the", "16s rrna and the mt", "rrna and the mt nd6", "and the mt nd6 mrna", "mt nd6 mrna and participates", "nd6 mrna and participates in", "mrna and participates in their", "and participates in their processing", "participates in their processing and", "in their processing and expression", "processing and expression antonicka", "and expression antonicka and", "expression antonicka and shoubridge", "and shoubridge 2015 popow", "shoubridge 2015 popow et", "2015 popow et al.", "popow et al. 2015 .", "et al. 2015 . fastkd2", "al. 2015 . fastkd2 interacts", "2015 . fastkd2 interacts with", ". fastkd2 interacts with several", "fastkd2 interacts with several mitochondrial", "interacts with several mitochondrial proteins", "with several mitochondrial proteins including", "several mitochondrial proteins including mterfd1", "proteins including mterfd1 trub2", "mterfd1 trub2 wbscr16", "trub2 wbscr16 and", "and ngrn antonicka et", "ngrn antonicka et al.", "antonicka et al. 2017 .", "et al. 2017 .
              fastkd3", "al. 2017 .
              fastkd3 increases", "2017 .
              fastkd3 increases levels", ".
              fastkd3 increases levels of", "
              fastkd3 increases levels of five", "increases levels of five mitochondrial", "levels of five mitochondrial mrnas", "five mitochondrial mrnas mt", "mitochondrial mrnas mt nd2", "mt nd2 mt nd3", "mt nd3 mt cyb", "mt cyb mt co2", "mt co2 and the", "co2 and the mt", "and the mt atp8/6 bicistronic", "the mt atp8/6 bicistronic mrna", "atp8/6 bicistronic mrna and", "bicistronic mrna and increases", "mrna and increases translation", "and increases translation of mt", "increases translation of mt co1", "translation of mt co1 mrna", "of mt co1 mrna through", "mt co1 mrna through uncharacterized", "co1 mrna through uncharacterized mechanisms", "through uncharacterized mechanisms boehm", "uncharacterized mechanisms boehm et", "mechanisms boehm et al.", "et al. 2016 ohkubo", "al. 2016 ohkubo et", "2016 ohkubo et al.", "ohkubo et al. 2021 .
              tbrg4", "al. 2021 .
              tbrg4 fastkd4", ".
              tbrg4 fastkd4 binds", "fastkd4 binds most rnas", "binds most rnas transcribed from", "most rnas transcribed from the", "rnas transcribed from the h", "transcribed from the h strand", "from the h strand and", "the h strand and enhances", "h strand and enhances the", "strand and enhances the expression", "and enhances the expression levels", "enhances the expression levels of", "the expression levels of mt", "expression levels of mt atp8/6", "of mt atp8/6 mt", "mt atp8/6 mt co1", "mt co1 mt co2", "mt co2 mt co3", "mt co3 mt nd3", "mt cyb and mt", "cyb and mt nd5", "mt nd5 mrnas wolf", "nd5 mrnas wolf and", "mrnas wolf and mootha", "and mootha 2014 boehm", "mootha 2014 boehm et", "2014 boehm et al.", "et al. 2017 ohkubo", "al. 2017 ohkubo et", "2017 ohkubo et al.", "ohkubo et al. 2021 .", "et al. 2021 . tbrg4", "al. 2021 . tbrg4 stabilizes", "2021 . tbrg4 stabilizes mt", ". tbrg4 stabilizes mt co1", "stabilizes mt co1 mt", "mt co1 mt nd3", "mt nd3 and mt", "nd3 and mt co2", "and mt co2 mrnas and", "mt co2 mrnas and assists", "co2 mrnas and assists the", "mrnas and assists the processing", "and assists the processing of", "assists the processing of mt", "the processing of mt nd5", "processing of mt nd5 and", "of mt nd5 and mt", "mt nd5 and mt cyb", "nd5 and mt cyb mrnas", "mt cyb mrnas boehm", "cyb mrnas boehm et", "mrnas boehm et al.", "ohkubo et al. 2021 .
              fastkd5", "et al. 2021 .
              fastkd5 binds", "al. 2021 .
              fastkd5 binds 12s", "2021 .
              fastkd5 binds 12s rrna", ".
              fastkd5 binds 12s rrna and", "binds 12s rrna and all", "12s rrna and all mrnas", "rrna and all mrnas except", "and all mrnas except mt", "all mrnas except mt nd3", "mrnas except mt nd3 and", "except mt nd3 and reduces", "mt nd3 and reduces levels", "nd3 and reduces levels of", "and reduces levels of mt", "reduces levels of mt atp8/6", "mt co1 mt co3", "mt co3 mt nd5", "mt cyb mrnas antonicka", "cyb mrnas antonicka and", "mrnas antonicka and shoubridge", "and shoubridge 2015 ohkubo", "shoubridge 2015 ohkubo et", "2015 ohkubo et al.", "et al. 2021 . ." ] }, { "record_id": "GLY_000594_1_2101", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9820960", "r hsa", "hsa 9820960", "r hsa 9820960" ] }, { "record_id": "GLY_000594_1_2101", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "respiratory syncytial", "syncytial virus", "attachment and", "and entry", "respiratory syncytial virus", "virus rsv", "rsv attachment", "attachment and entry", "syncytial virus rsv", "rsv attachment and", "respiratory syncytial virus rsv", "virus rsv attachment", "rsv attachment and entry", "the entry", "entry of", "of human", "human respiratory", "into host", "host cells", "cells involves", "involves attachment", "attachment of", "of the", "the virion", "virion to", "to the", "the host", "host cell", "cell surface", "through interaction", "interaction of", "of viral", "viral envelope", "envelope proteins", "proteins with", "with host", "cell attachment", "attachment factors", "and fusion", "fusion of", "the viral", "viral membrane", "membrane with", "with the", "cell membrane.", "membrane. the", "the g", "g glycoprotein", "glycoprotein is", "is the", "the attachment", "attachment protein", "protein that", "that interacts", "interacts with", "with surface", "surface molecules", "molecules of", "enabling the", "the rsv", "rsv virions", "virions to", "to bind", "bind to", "to their", "their target", "target cells.", "cells. while", "while the", "the f", "f glycoprotein", "glycoprotein may", "may facilitate", "facilitate attachment", "its primary", "primary function", "function is", "is to", "to promote", "promote fusion", "viral and", "and host", "cell membranes.", "membranes. the", "the sh", "sh protein", "protein is", "is dispensable", "dispensable for", "for entry.", "entry. for", "for review", "please refer", "refer to", "to battles", "battles and", "and mclellan", "mclellan 2019.

              using", "2019.

              using human", "human primary", "primary airway", "airway epithelial", "epithelial cell", "cell cultures", "it was", "was established", "established that", "that rsv", "rsv efficiently", "efficiently infects", "infects the", "the airway", "airway epithelium", "epithelium from", "from the", "the luminal", "luminal surface", "surface and", "and specifically", "specifically targets", "targets ciliated", "ciliated airway", "epithelial cells.", "cells. in", "in the", "the absence", "absence of", "of immune", "immune response", "rsv causes", "causes no", "no obvious", "obvious cytopathology", "zhang et", "et al.", "al. 2002", "2002 .

              in", ".

              in addition", "addition to", "to ciliated", "ciliated respiratory", "respiratory epithelial", "epithelial cells", "rsv may", "may infect", "infect granulocytes", "granulocytes and", "and cause", "cause a", "a delay", "delay in", "in constitutive", "constitutive apoptosis", "apoptosis of", "of neutrophils", "neutrophils and", "and eosinophils", "lindemans et", "al. 2006", "2006 .", ". rsv", "rsv can", "can also", "also infect", "infect neonatal", "neonatal specific", "specific regulatory", "regulatory b", "b cells", "which may", "may contribute", "contribute to", "to high", "high viral", "viral load", "load and", "and disease", "disease severity", "severity in", "in infants", "zhivaki et", "al. 2017", "2017 .", "the entry of", "entry of human", "of human respiratory", "human respiratory syncytial", "rsv into", "into host cells", "host cells involves", "cells involves attachment", "involves attachment of", "attachment of the", "of the virion", "the virion to", "virion to the", "to the host", "the host cell", "host cell surface", "surface through", "through interaction of", "interaction of viral", "of viral envelope", "viral envelope proteins", "envelope proteins with", "proteins with host", "with host cell", "host cell attachment", "cell attachment factors", "factors and", "and fusion of", "fusion of the", "of the viral", "the viral membrane", "viral membrane with", "membrane with the", "with the host", "host cell membrane.", "cell membrane. the", "membrane. the g", "the g glycoprotein", "g glycoprotein is", "glycoprotein is the", "is the attachment", "the attachment protein", "attachment protein that", "protein that interacts", "that interacts with", "interacts with surface", "with surface molecules", "surface molecules of", "molecules of the", "of the host", "the host cells", "cells enabling", "enabling the rsv", "the rsv virions", "rsv virions to", "virions to bind", "to bind to", "bind to their", "to their target", "their target cells.", "target cells. while", "cells. while the", "while the f", "the f glycoprotein", "f glycoprotein may", "glycoprotein may facilitate", "may facilitate attachment", "attachment its", "its primary function", "primary function is", "function is to", "is to promote", "to promote fusion", "promote fusion of", "the viral and", "viral and host", "and host cell", "host cell membranes.", "cell membranes. the", "membranes. the sh", "the sh protein", "sh protein is", "protein is dispensable", "is dispensable for", "dispensable for entry.", "for entry. for", "entry. for review", "review please", "please refer to", "refer to battles", "to battles and", "battles and mclellan", "and mclellan 2019.

              using", "mclellan 2019.

              using human", "2019.

              using human primary", "human primary airway", "primary airway epithelial", "airway epithelial cell", "epithelial cell cultures", "cultures it", "it was established", "was established that", "established that rsv", "that rsv efficiently", "rsv efficiently infects", "efficiently infects the", "infects the airway", "the airway epithelium", "airway epithelium from", "epithelium from the", "from the luminal", "the luminal surface", "luminal surface and", "surface and specifically", "and specifically targets", "specifically targets ciliated", "targets ciliated airway", "ciliated airway epithelial", "airway epithelial cells.", "epithelial cells. in", "cells. in the", "in the absence", "the absence of", "absence of immune", "of immune response", "response rsv", "rsv causes no", "causes no obvious", "no obvious cytopathology", "cytopathology zhang", "zhang et al.", "et al. 2002", "al. 2002 .

              in", "2002 .

              in addition", ".

              in addition to", "addition to ciliated", "to ciliated respiratory", "ciliated respiratory epithelial", "respiratory epithelial cells", "cells rsv", "rsv may infect", "may infect granulocytes", "infect granulocytes and", "granulocytes and cause", "and cause a", "cause a delay", "a delay in", "delay in constitutive", "in constitutive apoptosis", "constitutive apoptosis of", "apoptosis of neutrophils", "of neutrophils and", "neutrophils and eosinophils", "eosinophils lindemans", "lindemans et al.", "et al. 2006", "al. 2006 .", "2006 . rsv", ". rsv can", "rsv can also", "can also infect", "also infect neonatal", "infect neonatal specific", "neonatal specific regulatory", "specific regulatory b", "regulatory b cells", "cells which", "which may contribute", "may contribute to", "contribute to high", "to high viral", "high viral load", "viral load and", "load and disease", "and disease severity", "disease severity in", "severity in infants", "infants zhivaki", "zhivaki et al.", "et al. 2017", "al. 2017 .", "the entry of human", "entry of human respiratory", "of human respiratory syncytial", "human respiratory syncytial virus", "rsv into host", "into host cells involves", "host cells involves attachment", "cells involves attachment of", "involves attachment of the", "attachment of the virion", "of the virion to", "the virion to the", "virion to the host", "to the host cell", "the host cell surface", "cell surface through", "surface through interaction", "through interaction of viral", "interaction of viral envelope", "of viral envelope proteins", "viral envelope proteins with", "envelope proteins with host", "proteins with host cell", "with host cell attachment", "host cell attachment factors", "attachment factors and", "factors and fusion", "and fusion of the", "fusion of the viral", "of the viral membrane", "the viral membrane with", "viral membrane with the", "membrane with the host", "with the host cell", "the host cell membrane.", "host cell membrane. the", "cell membrane. the g", "membrane. the g glycoprotein", "the g glycoprotein is", "g glycoprotein is the", "glycoprotein is the attachment", "is the attachment protein", "the attachment protein that", "attachment protein that interacts", "protein that interacts with", "that interacts with surface", "interacts with surface molecules", "with surface molecules of", "surface molecules of the", "molecules of the host", "of the host cells", "host cells enabling", "cells enabling the", "enabling the rsv virions", "the rsv virions to", "rsv virions to bind", "virions to bind to", "to bind to their", "bind to their target", "to their target cells.", "their target cells. while", "target cells. while the", "cells. while the f", "while the f glycoprotein", "the f glycoprotein may", "f glycoprotein may facilitate", "glycoprotein may facilitate attachment", "facilitate attachment its", "attachment its primary", "its primary function is", "primary function is to", "function is to promote", "is to promote fusion", "to promote fusion of", "promote fusion of the", "of the viral and", "the viral and host", "viral and host cell", "and host cell membranes.", "host cell membranes. the", "cell membranes. the sh", "membranes. the sh protein", "the sh protein is", "sh protein is dispensable", "protein is dispensable for", "is dispensable for entry.", "dispensable for entry. for", "for entry. for review", "for review please", "review please refer", "please refer to battles", "refer to battles and", "to battles and mclellan", "battles and mclellan 2019.

              using", "and mclellan 2019.

              using human", "mclellan 2019.

              using human primary", "2019.

              using human primary airway", "human primary airway epithelial", "primary airway epithelial cell", "airway epithelial cell cultures", "cell cultures it", "cultures it was", "it was established that", "was established that rsv", "established that rsv efficiently", "that rsv efficiently infects", "rsv efficiently infects the", "efficiently infects the airway", "infects the airway epithelium", "the airway epithelium from", "airway epithelium from the", "epithelium from the luminal", "from the luminal surface", "the luminal surface and", "luminal surface and specifically", "surface and specifically targets", "and specifically targets ciliated", "specifically targets ciliated airway", "targets ciliated airway epithelial", "ciliated airway epithelial cells.", "airway epithelial cells. in", "epithelial cells. in the", "cells. in the absence", "in the absence of", "the absence of immune", "absence of immune response", "immune response rsv", "response rsv causes", "rsv causes no obvious", "causes no obvious cytopathology", "obvious cytopathology zhang", "cytopathology zhang et", "zhang et al. 2002", "et al. 2002 .

              in", "al. 2002 .

              in addition", "2002 .

              in addition to", ".

              in addition to ciliated", "addition to ciliated respiratory", "to ciliated respiratory epithelial", "ciliated respiratory epithelial cells", "epithelial cells rsv", "cells rsv may", "rsv may infect granulocytes", "may infect granulocytes and", "infect granulocytes and cause", "granulocytes and cause a", "and cause a delay", "cause a delay in", "a delay in constitutive", "delay in constitutive apoptosis", "in constitutive apoptosis of", "constitutive apoptosis of neutrophils", "apoptosis of neutrophils and", "of neutrophils and eosinophils", "and eosinophils lindemans", "eosinophils lindemans et", "lindemans et al. 2006", "et al. 2006 .", "al. 2006 . rsv", "2006 . rsv can", ". rsv can also", "rsv can also infect", "can also infect neonatal", "also infect neonatal specific", "infect neonatal specific regulatory", "neonatal specific regulatory b", "specific regulatory b cells", "b cells which", "cells which may", "which may contribute to", "may contribute to high", "contribute to high viral", "to high viral load", "high viral load and", "viral load and disease", "load and disease severity", "and disease severity in", "disease severity in infants", "in infants zhivaki", "infants zhivaki et", "zhivaki et al. 2017", "et al. 2017 .", "the entry of human respiratory", "entry of human respiratory syncytial", "of human respiratory syncytial virus", "virus rsv into", "rsv into host cells", "into host cells involves attachment", "host cells involves attachment of", "cells involves attachment of the", "involves attachment of the virion", "attachment of the virion to", "of the virion to the", "the virion to the host", "virion to the host cell", "to the host cell surface", "host cell surface through", "cell surface through interaction", "surface through interaction of", "through interaction of viral envelope", "interaction of viral envelope proteins", "of viral envelope proteins with", "viral envelope proteins with host", "envelope proteins with host cell", "proteins with host cell attachment", "with host cell attachment factors", "cell attachment factors and", "attachment factors and fusion", "factors and fusion of", "and fusion of the viral", "fusion of the viral membrane", "of the viral membrane with", "the viral membrane with the", "viral membrane with the host", "membrane with the host cell", "with the host cell membrane.", "the host cell membrane. the", "host cell membrane. the g", "cell membrane. the g glycoprotein", "membrane. the g glycoprotein is", "the g glycoprotein is the", "g glycoprotein is the attachment", "glycoprotein is the attachment protein", "is the attachment protein that", "the attachment protein that interacts", "attachment protein that interacts with", "protein that interacts with surface", "that interacts with surface molecules", "interacts with surface molecules of", "with surface molecules of the", "surface molecules of the host", "molecules of the host cells", "the host cells enabling", "host cells enabling the", "cells enabling the rsv", "enabling the rsv virions to", "the rsv virions to bind", "rsv virions to bind to", "virions to bind to their", "to bind to their target", "bind to their target cells.", "to their target cells. while", "their target cells. while the", "target cells. while the f", "cells. while the f glycoprotein", "while the f glycoprotein may", "the f glycoprotein may facilitate", "f glycoprotein may facilitate attachment", "may facilitate attachment its", "facilitate attachment its primary", "attachment its primary function", "its primary function is to", "primary function is to promote", "function is to promote fusion", "is to promote fusion of", "to promote fusion of the", "promote fusion of the viral", "fusion of the viral and", "of the viral and host", "the viral and host cell", "viral and host cell membranes.", "and host cell membranes. the", "host cell membranes. the sh", "cell membranes. the sh protein", "membranes. the sh protein is", "the sh protein is dispensable", "sh protein is dispensable for", "protein is dispensable for entry.", "is dispensable for entry. for", "dispensable for entry. for review", "entry. for review please", "for review please refer", "review please refer to", "please refer to battles and", "refer to battles and mclellan", "to battles and mclellan 2019.

              using", "battles and mclellan 2019.

              using human", "and mclellan 2019.

              using human primary", "mclellan 2019.

              using human primary airway", "2019.

              using human primary airway epithelial", "human primary airway epithelial cell", "primary airway epithelial cell cultures", "epithelial cell cultures it", "cell cultures it was", "cultures it was established", "it was established that rsv", "was established that rsv efficiently", "established that rsv efficiently infects", "that rsv efficiently infects the", "rsv efficiently infects the airway", "efficiently infects the airway epithelium", "infects the airway epithelium from", "the airway epithelium from the", "airway epithelium from the luminal", "epithelium from the luminal surface", "from the luminal surface and", "the luminal surface and specifically", "luminal surface and specifically targets", "surface and specifically targets ciliated", "and specifically targets ciliated airway", "specifically targets ciliated airway epithelial", "targets ciliated airway epithelial cells.", "ciliated airway epithelial cells. in", "airway epithelial cells. in the", "epithelial cells. in the absence", "cells. in the absence of", "in the absence of immune", "the absence of immune response", "of immune response rsv", "immune response rsv causes", "response rsv causes no", "rsv causes no obvious cytopathology", "no obvious cytopathology zhang", "obvious cytopathology zhang et", "cytopathology zhang et al.", "zhang et al. 2002 .

              in", "et al. 2002 .

              in addition", "al. 2002 .

              in addition to", "2002 .

              in addition to ciliated", ".

              in addition to ciliated respiratory", "addition to ciliated respiratory epithelial", "to ciliated respiratory epithelial cells", "respiratory epithelial cells rsv", "epithelial cells rsv may", "cells rsv may infect", "rsv may infect granulocytes and", "may infect granulocytes and cause", "infect granulocytes and cause a", "granulocytes and cause a delay", "and cause a delay in", "cause a delay in constitutive", "a delay in constitutive apoptosis", "delay in constitutive apoptosis of", "in constitutive apoptosis of neutrophils", "constitutive apoptosis of neutrophils and", "apoptosis of neutrophils and eosinophils", "neutrophils and eosinophils lindemans", "and eosinophils lindemans et", "eosinophils lindemans et al.", "lindemans et al. 2006 .", "et al. 2006 . rsv", "al. 2006 . rsv can", "2006 . rsv can also", ". rsv can also infect", "rsv can also infect neonatal", "can also infect neonatal specific", "also infect neonatal specific regulatory", "infect neonatal specific regulatory b", "neonatal specific regulatory b cells", "regulatory b cells which", "b cells which may", "cells which may contribute", "which may contribute to high", "may contribute to high viral", "contribute to high viral load", "to high viral load and", "high viral load and disease", "viral load and disease severity", "load and disease severity in", "and disease severity in infants", "severity in infants zhivaki", "in infants zhivaki et", "infants zhivaki et al.", "zhivaki et al. 2017 ." ] }, { "record_id": "GLY_000594_1_2102", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9828806", "r hsa", "hsa 9828806", "r hsa 9828806" ] }, { "record_id": "GLY_000594_1_2102", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "maturation of", "of hrsv", "hrsv a", "a proteins", "maturation of hrsv", "of hrsv a", "hrsv a proteins", "maturation of hrsv a", "of hrsv a proteins", "maturation of hrsv a proteins", 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2014 . nephronectin", ". nephronectin npnt", "npnt secreted by", "secreted by the nephric", "by the nephric duct", "the nephric duct interacts", "nephric duct interacts with", "duct interacts with integrin", "interacts with integrin alpha8/beta1", "integrin alpha8/beta1 itga8", "itga8 on the", "on the metanephric mesenchyme", "the metanephric mesenchyme to", "metanephric mesenchyme to activate", "mesenchyme to activate expression", "to activate expression of", "activate expression of gdnf", "expression of gdnf in", "of gdnf in the", "gdnf in the metanephric", "in the metanephric mesenchyme", "metanephric mesenchyme brandenberger", "mesenchyme brandenberger et", "brandenberger et al. 2001", "al. 2001 linton", "2001 linton et", "linton et al. 2007", "et al. 2007 .", "al. 2007 . gdnf", "2007 . gdnf secreted", ". gdnf secreted by", "gdnf secreted by the", "secreted by the metanephric", "by the metanephric mesenchyme", "the metanephric mesenchyme then", "metanephric mesenchyme then binds", "mesenchyme then binds and", "then binds and activates", "binds and activates the", "and activates the ret", "activates the ret tyrosine", "the ret tyrosine kinase", "ret tyrosine kinase located", "tyrosine kinase located in", "kinase located in the", "located in the plasma", "in the plasma membrane", "the plasma membrane of", "plasma membrane of nephric", "membrane of nephric duct", "of nephric duct cells", "duct cells trupp", "cells trupp et", "trupp et al. 1996", "al. 1996 majumdar", "1996 majumdar et", "majumdar et al. 2003", "et al. 2003 .", "al. 2003 . ret", "2003 . ret activates", ". ret activates expression", "ret activates expression of", "activates expression of wnt11", "expression of wnt11 in", "of wnt11 in the", "wnt11 in the nephric", "the nephric duct to", "nephric duct to regulate", "duct to regulate differentiation", "regulate differentiation majumdar", "differentiation majumdar et", "al. 2003 . the", "2003 . the extent", ". the extent of", "the extent of kidney", "extent of kidney development", "of kidney development is", "kidney development is circumscribed", "development is circumscribed by", "is circumscribed by inhibitory", "circumscribed by inhibitory signals", "by inhibitory signals provided", "inhibitory signals provided by", "signals provided by robo2:slit", "provided by robo2:slit at", "by robo2:slit at the", "robo2:slit at the duct", "at the duct mesenchyme", "the duct mesenchyme interface", "mesenchyme interface wainwright", "interface wainwright et", "wainwright et al. 2015", "al. 2015 and", "2015 and by", "and by foxc1 2", "by foxc1 2 from", "foxc1 2 from the", "2 from the paraxial", "from the paraxial mesoderm.", "visible kidney development initiates with", "kidney development initiates with the", "development initiates with the formation", "initiates with the formation of", "with the formation of the", "the formation of the pronephros", "formation of the pronephros and", "of the pronephros and then", "the pronephros and then the", "pronephros and then the mesonephros", "then the mesonephros reviewed", "the mesonephros reviewed in", "mesonephros reviewed in mcmahon", "reviewed in mcmahon 2016 .", "in mcmahon 2016 . in", "mcmahon 2016 . in amniotes", "2016 . in amniotes these", ". in amniotes these are", "in amniotes these are transitory", "amniotes these are transitory structures", "these are transitory structures that", "are transitory structures that are", "transitory structures that are superseded", "structures that are superseded by", "that are superseded by formation", "are superseded by formation of", "superseded by formation of the", "by formation of the metanephros", "of the metanephros the", "the metanephros the functional", "metanephros the functional kidney", "the functional kidney that persists", "functional kidney that persists into", "kidney that persists into adulthood.", "that persists into adulthood. the", "persists into adulthood. the nephric", "into adulthood. the nephric duct", "adulthood. the nephric duct appears", "the nephric duct appears during", "nephric duct appears during development", "duct appears during development of", "appears during development of the", "during development of the pronephros", "development of the pronephros and", "the pronephros and then extends", "pronephros and then extends caudally", "and then extends caudally in", "then extends caudally in the", "extends caudally in the mesonephros", "in the mesonephros inducing", "the mesonephros inducing the", "mesonephros inducing the formation", "inducing the formation of mesonephric", "the formation of mesonephric tubules", "formation of mesonephric tubules that", "of mesonephric tubules that drain", "mesonephric tubules that drain into", "tubules that drain into the", "that drain into the nephric", "drain into the nephric duct", "into the nephric duct and", "the nephric duct and provide", "nephric duct and provide blood", "duct and provide blood filtration", "and provide blood filtration in", "provide blood filtration in the", "blood filtration in the embryo.", "in the embryo. the", "the embryo. the mesonephric", "embryo. the mesonephric duct", "the mesonephric duct is also", "mesonephric duct is also called", "duct is also called the", "is also called the wolffian", "also called the wolffian duct.", "called the wolffian duct.
              subsequently", "wolffian duct.
              subsequently the", "duct.
              subsequently the metanephros", "
              subsequently the metanephros is", "the metanephros is initiated by", "metanephros is initiated by formation", "is initiated by formation of", "initiated by formation of the", "by formation of the ureteric", "of the ureteric bud in", "the ureteric bud in the", "ureteric bud in the nephric", "bud in the nephric duct", "in the nephric duct due", "the nephric duct due to", "nephric duct due to the", "duct due to the interaction", "due to the interaction between", "to the interaction between the", "the interaction between the nephric", "interaction between the nephric duct", "between the nephric duct and", "the nephric duct and the", "nephric duct and the adjacent", "duct and the adjacent metanephric", "and the adjacent metanephric mesenchyme.", "the adjacent metanephric mesenchyme. the", "adjacent metanephric mesenchyme. the ureteric", "metanephric mesenchyme. the ureteric bud", "mesenchyme. the ureteric bud will", "the ureteric bud will grow", "ureteric bud will grow to", "bud will grow to become", "will grow to become the", "grow to become the ureter", "become the ureter branch", "the ureter branch further", "branch further and induce", "further and induce the", "and induce the formation of", "induce the formation of nephrons", "the formation of nephrons and", "formation of nephrons and collecting", "of nephrons and collecting ducts", "nephrons and collecting ducts at", "and collecting ducts at the", "collecting ducts at the termini", "ducts at the termini of", "at the termini of the", "the termini of the branches", "of the branches reviewed", "the branches reviewed in", "branches reviewed in costantini", "reviewed in costantini 2012 .", "in costantini 2012 . development", "costantini 2012 . development of", "2012 . development of the", ". development of the ureteric", "development of the ureteric bulge", "of the ureteric bulge is", "the ureteric bulge is regulated", "ureteric bulge is regulated by", "bulge is regulated by reciprocal", "is regulated by reciprocal signals", "regulated by reciprocal signals passed", "by reciprocal signals passed between", "reciprocal signals passed between the", "signals passed between the nephric", "passed between the nephric duct", "nephric duct and the metanephric", "duct and the metanephric mesenchyme", "the metanephric mesenchyme reviewed", "metanephric mesenchyme reviewed in", "mesenchyme reviewed in marcotte", "reviewed in marcotte et al.", "in marcotte et al. 2014", "marcotte et al. 2014 .", "et al. 2014 . nephronectin", "2014 . nephronectin npnt", "nephronectin npnt secreted", "npnt secreted by the", "secreted by the nephric duct", "by the nephric duct interacts", "the nephric duct interacts with", "nephric duct interacts with integrin", "duct interacts with integrin alpha8/beta1", "with integrin alpha8/beta1 itga8", "alpha8/beta1 itga8 on", "itga8 on the metanephric", "on the metanephric mesenchyme to", "the metanephric mesenchyme to activate", "metanephric mesenchyme to activate expression", "mesenchyme to activate expression of", "to activate expression of gdnf", "activate expression of gdnf in", "expression of gdnf in the", "of gdnf in the metanephric", "gdnf in the metanephric mesenchyme", "the metanephric mesenchyme brandenberger", "metanephric mesenchyme brandenberger et", "mesenchyme brandenberger et al.", "et al. 2001 linton", "al. 2001 linton et", "2001 linton et al.", "linton et al. 2007 .", "et al. 2007 . gdnf", "al. 2007 . gdnf secreted", "2007 . gdnf secreted by", ". gdnf secreted by the", "gdnf secreted by the metanephric", "secreted by the metanephric mesenchyme", "by the metanephric mesenchyme then", "the metanephric mesenchyme then binds", "metanephric mesenchyme then binds and", "mesenchyme then binds and activates", "then binds and activates the", "binds and activates the ret", "and activates the ret tyrosine", "activates the ret tyrosine kinase", "the ret tyrosine kinase located", "ret tyrosine kinase located in", "tyrosine kinase located in the", "kinase located in the plasma", "located in the plasma membrane", "in the plasma membrane of", "the plasma membrane of nephric", "plasma membrane of nephric duct", "membrane of nephric duct cells", "nephric duct cells trupp", "duct cells trupp et", "cells trupp et al.", "et al. 1996 majumdar", "al. 1996 majumdar et", "1996 majumdar et al.", "majumdar et al. 2003 .", "et al. 2003 . ret", "al. 2003 . ret activates", "2003 . ret activates expression", ". ret activates expression of", "ret activates expression of wnt11", "activates expression of wnt11 in", "expression of wnt11 in the", "of wnt11 in the nephric", "wnt11 in the nephric duct", "in the nephric duct to", "the nephric duct to regulate", "nephric duct to regulate differentiation", "to regulate differentiation majumdar", "regulate differentiation majumdar et", "differentiation majumdar et al.", "et al. 2003 . the", "al. 2003 . the extent", "2003 . the extent of", ". the extent of kidney", "the extent of kidney development", "extent of kidney development is", "of kidney development is circumscribed", "kidney development is circumscribed by", "development is circumscribed by inhibitory", "is circumscribed by inhibitory signals", "circumscribed by inhibitory signals provided", "by inhibitory signals provided by", "inhibitory signals provided by robo2:slit", "signals provided by robo2:slit at", "provided by robo2:slit at the", "by robo2:slit at the duct", "robo2:slit at the duct mesenchyme", "at the duct mesenchyme interface", "duct mesenchyme interface wainwright", "mesenchyme interface wainwright et", "interface wainwright et al.", "et al. 2015 and", "al. 2015 and by", "2015 and by foxc1", "and by foxc1 2 from", "by foxc1 2 from the", "foxc1 2 from the paraxial", "2 from the paraxial mesoderm." ] }, { "record_id": "GLY_000594_1_2104", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9831926", "r hsa", "hsa 9831926", "r hsa 9831926" ] }, { "record_id": "GLY_000594_1_2104", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "nephron development", "a nephron", "nephron of", "of an", "an amniote", "amniote such", "such as", "as mouse", "mouse or", "or human", "human comprises", "comprises the", "the glomerulus", "glomerulus where", "where small", "small molecules", "molecules are", "are filtered", "filtered out", "out of", "of the", "the blood", "the proximal", "proximal tubule", "tubule and", "and the", "the loop", "loop of", "of henle", "henle where", "are selectively", "selectively reabsorbed", "the thick", "thick ascending", "ascending limb", "the macula", "macula densa", "the distal", "distal convoluted", "convoluted tubule", "the connecting", "connecting tubule", "the collecting", "collecting duct", "duct which", "which drains", "drains into", "into the", "the ureter.
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place", "differentiating in place analysis", "in place analysis of", "place analysis of cellular", "analysis of cellular migration indicates", "of cellular migration indicates that", "cellular migration indicates that progenitors", "migration indicates that progenitors are", "indicates that progenitors are recruited", "that progenitors are recruited from", "progenitors are recruited from the", "are recruited from the mesenchyme", "recruited from the mesenchyme to", "from the mesenchyme to the", "the mesenchyme to the developing", "mesenchyme to the developing epithelial", "to the developing epithelial elements", "the developing epithelial elements of", "developing epithelial elements of the", "epithelial elements of the nephron", "of the nephron lindstrom", "the nephron lindstrom et", "nephron lindstrom et al.", "lindstrom et al. 2018 .", "et al. 2018 . the", "al. 2018 . the transcriptional", "2018 . the transcriptional program", ". the transcriptional program that", "the 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              the", "2022 .
              the hexameric", ".
              the hexameric lonp1", "hexameric lonp1 complex", "complex which", "which is homologous", "is homologous to", "homologous to lon", "to lon proteases", "lon proteases of", "proteases of eubacteria", "of eubacteria such", "eubacteria such as", "such as e.", "as e. coli", "coli binds", "binds substrate proteins", "substrate proteins in", "proteins in the", "the matrix and", "matrix and inner", "and inner membrane", "membrane unfolds", "unfolds them in", "them in an", "in an atp", "an atp dependent", "atp dependent mechanism", "mechanism and", "and degrades them", "them reviewed", "reviewed in gibellini", "in gibellini et", "gibellini et al.", "al. 2020 .", "2020 . lonp1", ". lonp1 also", "lonp1 also acts", "also acts as", "acts as an", "as an atp", "atp dependent chaperone", "dependent chaperone that", "chaperone that is", "that is independent", "is independent of", "independent of its", "of its protease", "its protease function", "function reviewed", "al. 2020 .
              like", "2020 .
              like lonp1", "lonp1 the", "the clpxp complex", "clpxp complex unfolds", "complex unfolds matrix", "unfolds matrix proteins", "matrix proteins in", "proteins in an", "atp dependent reaction", "dependent reaction and", "reaction and degrades", "them however", "however the", "the atpase/unfolding function", "atpase/unfolding function and", "function and the", "and the protease", "the protease function", "protease function are", "function are performed", "are performed by", "performed by separate", "by separate subunits", "subunits with", "with clpx hexamers", "clpx hexamers unfolding", "hexamers unfolding substrate", "unfolding substrate proteins", "substrate proteins and", "proteins and translocating", "and translocating them", "translocating them to", "them to clpp", "to clpp tetradecamers", "clpp tetradecamers for", "tetradecamers for processive", "for processive degradation", "degradation reviewed", "reviewed in mabanglo", "in mabanglo et", "mabanglo et al.", "2021 mabanglo", "mabanglo and houry", "and houry 2022", "houry 2022 .
              afg3l2", ".
              afg3l2 m", "aaa+ forms", "forms either homohexamers", "either homohexamers or", "homohexamers or heterohexamers", "or heterohexamers with", "heterohexamers with its", "with its paralog", "its paralog spg7", "spg7 paraplegin", "paraplegin that", "that are anchored", "are anchored in", "anchored in the", "membrane and protrude", "and protrude into", "protrude into the", "matrix reviewed", "reviewed in patron", "in patron et", "patron et al.", "et al. 2018", "2018 steele", "steele and glynn", "and glynn 2019", "2019 zhang", "zhang and mao", "and mao 2020", "mao 2020 .", "2020 . the", ". the substrate", "the substrate protein", "substrate protein enters", "protein enters the", "enters the central", "the central channel", "central channel formed", "channel formed by", "formed by the", "by the atpase", "the atpase domains", "atpase domains of", "domains of afg3l2", "of afg3l2 and", "afg3l2 and is", "and is unfolded", "is unfolded and", "unfolded and translocated", "and translocated to", "translocated to the", "to the pore", "the pore formed", "pore formed by", "by the protease", "the protease domains", "domains where", "where it is", "it is degraded", "degraded reviewed", "reviewed inzhang and", "inzhang and mao", "2020 .
              like", ".
              like afg3l2", "afg3l2 yme1l1", "yme1l1 yme1l", "yme1l i", "aaa+ is", "is a homohexameric", "a homohexameric complex", "homohexameric complex that", "complex that is", "that is anchored", "is anchored in", "membrane however", "however yme1l1", "yme1l1 protrudes into", "protrudes into the", "intermembrane space where", "space where it", "where it unfolds", "it unfolds substrate", "unfolds substrate proteins", "substrate proteins of", "proteins of the", "of the intermembrane", "intermembrane space and", "space and inner", "inner membrane in", "membrane in an", "reaction and then", "and then degrades", "then degrades them", "reviewed in steele", "in steele and", "2019 ohba", "ohba et al.", "2020 zhang", "mao 2020 .
              htra2", ".
              htra2 omi", "omi forms", "forms soluble trimeric", "soluble trimeric complexes", "trimeric complexes in", "complexes in the", "intermembrane space that", "space that degrade", "that degrade substrate", "degrade substrate proteins", "proteins notably", "notably amyloid precursor", "amyloid precursor proteins", "precursor proteins that", "proteins that are", "that are translocated", "are translocated to", "to the intermembrane", "and inner membrane.", "inner membrane. htra2", "membrane. htra2 released", "htra2 released from", "released from mitochondria", "from mitochondria into", "mitochondria into the", "into the cytosol", "the cytosol also", "cytosol also participates", "also participates in", "participates in regulating", "in regulating apoptosis", "apoptosis reviewed", "reviewed in vande", "in vande walle", "vande walle et", "walle et al.", "et al. 2008", "al. 2008 .
              mutations", "2008 .
              mutations in", ".
              mutations in mitochondrial", "in mitochondrial proteases", "mitochondrial proteases cause", "proteases cause diseases", "diseases such", "such as spastic", "as spastic paraplegia", "paraplegia spg7", "ataxia afg3l2", "and parkinson's disease", "disease htra2", "that typically have", "typically have neurological", "have neurological symptoms", "neurological symptoms among", "symptoms among others", "others reviewed", "reviewed in su", "in su et", "su et al.", "2019 gomez", "gomez fabra gala", "fabra gala and", "gala and vogtle", "and vogtle 2021", "vogtle 2021 .", "mitochondrial proteases participate in", "proteases participate in proteostasis", "in proteostasis the", "proteostasis the regulation", "the regulation of proteins", "regulation of proteins to", "of proteins to maintain", "proteins to maintain a", "to maintain a functional", "maintain a functional proteome", "functional proteome by", "proteome by degrading", "degrading unfolded unassembled", "unassembled and oxidatively", "and oxidatively damaged proteins", "damaged proteins reviewed", "proteins reviewed in", "reviewed in ng et", "in ng et al.", "ng et al. 2021", "al. 2021 song", "2021 song et", "song et al. 2021", "et al. 2021 .", "al. 2021 . degradation", "2021 . degradation of", ". degradation of mitochondrial", "degradation of mitochondrial proteins", "of mitochondrial proteins by", "mitochondrial proteins by proteases", "proteins by proteases also", "by proteases also serves", "proteases also serves to", "also serves to regulate", "serves to regulate transcription", "to regulate transcription by", "regulate transcription by tfam", "by tfam oxidative", "tfam oxidative phosphorylation", "oxidative phosphorylation by electron", "phosphorylation by electron carriers", "electron carriers lipid", "carriers lipid translocation", "lipid translocation by prelid1", "translocation by prelid1 and", "by prelid1 and stard7", "and stard7 and", "stard7 and mitochondrial", "and mitochondrial fission and", "mitochondrial fission and fusion", "fission and fusion by", "and fusion by opa1", "fusion by opa1 and", "by opa1 and oma1", "and oma1 reviewed", "oma1 reviewed in", "reviewed in ahola et", "in ahola et al.", "ahola et al. 2019", "et al. 2019 .", "al. 2019 . because", "2019 . because of", ". because of the", "because of the bacterial", "of the bacterial origin", "the bacterial origin of", "bacterial origin of mitochondria", "of mitochondria they", "mitochondria they contain", "they contain a number", "contain a number of", "a number of bacterial", "number of bacterial type", "of bacterial type proteases", "type proteases including", "proteases including lonp1", "including lonp1 in the", "lonp1 in the matrix", "the matrix clpp:clpx", "clpxp in the", "the matrix htra2", "omi in the", "in the intermembrane space", "intermembrane space afg3l2", "space afg3l2 in", "afg3l2 in the mitochondrial", "in the mitochondrial inner", "the mitochondrial inner membrane", "mitochondrial inner membrane and", "inner membrane and protruding", "membrane and protruding into", "and protruding into the", "protruding into the matrix", "matrix and yme1l1", "and yme1l1 in the", "yme1l1 in the mitochondrial", "protruding into the intermembrane", "into the intermembrane space", "intermembrane space reviewed", "space reviewed in", "reviewed in deshwal et", "in deshwal et al.", "deshwal et al. 2020", "al. 2020 szczepanowska", "2020 szczepanowska and", "szczepanowska and trifunovic 2022", "and trifunovic 2022 .
              the", "trifunovic 2022 .
              the hexameric", "2022 .
              the hexameric lonp1", ".
              the hexameric lonp1 complex", "lonp1 complex which", "complex which is", "which is homologous to", "is homologous to lon", "homologous to lon proteases", "to lon proteases of", "lon proteases of eubacteria", "proteases of eubacteria such", "of eubacteria such as", "eubacteria such as e.", "such as e. coli", "e. coli binds", "coli binds substrate", "binds substrate proteins in", "substrate proteins in the", "proteins in the matrix", "in the matrix and", "the matrix and inner", "matrix and inner membrane", "inner membrane unfolds", "membrane unfolds them", "unfolds them in an", "them in an atp", "in an atp dependent", "an atp dependent mechanism", "dependent mechanism and", "mechanism and degrades", "degrades them reviewed", "them reviewed in", "reviewed in gibellini et", "in gibellini et al.", "gibellini et al. 2020", "et al. 2020 .", "al. 2020 . lonp1", "2020 . lonp1 also", ". lonp1 also acts", "lonp1 also acts as", "also acts as an", "acts as an atp", "as an atp dependent", "an atp dependent chaperone", "atp dependent chaperone that", "dependent chaperone that is", "chaperone that is independent", "that is independent of", "is independent of its", "independent of its protease", "of its protease function", "protease function reviewed", "function reviewed in", "et al. 2020 .
              like", "al. 2020 .
              like lonp1", ".
              like lonp1 the", "lonp1 the clpxp", "the clpxp complex unfolds", "clpxp complex unfolds matrix", "complex unfolds matrix proteins", "unfolds matrix proteins in", "matrix proteins in an", "proteins in an atp", "an atp dependent reaction", "atp dependent reaction and", "dependent reaction and degrades", "reaction and degrades them", "degrades them however", "however the atpase/unfolding", "the atpase/unfolding function and", "atpase/unfolding function and the", "function and the protease", "and the protease function", "the protease function are", "protease function are performed", "function are performed by", "are performed by separate", "performed by separate subunits", "separate subunits with", "subunits with clpx", "with clpx hexamers unfolding", "clpx hexamers unfolding substrate", "hexamers unfolding substrate proteins", "unfolding substrate proteins and", "substrate proteins and translocating", "proteins and translocating them", "and translocating them to", "translocating them to clpp", "them to clpp tetradecamers", "to clpp tetradecamers for", "clpp tetradecamers for processive", "tetradecamers for processive degradation", "processive degradation reviewed", "degradation reviewed in", "reviewed in mabanglo et", "in mabanglo et al.", "mabanglo et al. 2021", "al. 2021 mabanglo", "2021 mabanglo and", "mabanglo and houry 2022", "and houry 2022 .
              afg3l2", "2022 .
              afg3l2 m", ".
              afg3l2 m aaa+", "m aaa+ forms", "aaa+ forms either", "forms either homohexamers or", "either homohexamers or heterohexamers", "homohexamers or heterohexamers with", "or heterohexamers with its", "heterohexamers with its paralog", "with its paralog spg7", "paralog spg7 paraplegin", "paraplegin that are", "that are anchored in", "are anchored in the", "anchored in the mitochondrial", "inner membrane and protrude", "membrane and protrude into", "and protrude into the", "protrude into the matrix", "the matrix reviewed", "matrix reviewed in", "reviewed in patron et", "in patron et al.", "patron et al. 2018", "al. 2018 steele", "2018 steele and", "steele and glynn 2019", "glynn 2019 zhang", "2019 zhang and", "zhang and mao 2020", "and mao 2020 .", "mao 2020 . the", "2020 . the substrate", ". the substrate protein", "the substrate protein enters", "substrate protein enters the", "protein enters the central", "enters the central channel", "the central channel formed", "central channel formed by", "channel formed by the", "formed by the atpase", "by the atpase domains", "the atpase domains of", "atpase domains of afg3l2", "domains of afg3l2 and", "of afg3l2 and is", "afg3l2 and is unfolded", "and is unfolded and", "is unfolded and translocated", "unfolded and translocated to", "and translocated to the", "translocated to the pore", "to the pore formed", "the pore formed by", "pore formed by the", "formed by the protease", "by the protease domains", "protease domains where", "domains where it", "where it is degraded", "is degraded reviewed", "degraded reviewed inzhang", "reviewed inzhang and mao", "inzhang and mao 2020", "mao 2020 .
              like", "2020 .
              like afg3l2", "
              like afg3l2 yme1l1", "yme1l i aaa+", "i aaa+ is", "aaa+ is a", "is a homohexameric complex", "a homohexameric complex that", "homohexameric complex that is", "complex that is anchored", "that is anchored in", "is anchored in the", "inner membrane however", "however yme1l1 protrudes", "yme1l1 protrudes into the", "protrudes into the intermembrane", "the intermembrane space where", "intermembrane space where it", "space where it unfolds", "where it unfolds substrate", "it unfolds substrate proteins", "unfolds substrate proteins of", "substrate proteins of the", "proteins of the intermembrane", "of the intermembrane space", "the intermembrane space and", "intermembrane space and inner", "space and inner membrane", "and inner membrane in", "inner membrane in an", "membrane in an atp", "dependent reaction and then", "reaction and then degrades", "and then degrades them", "reviewed in steele and", "in steele and glynn", "glynn 2019 ohba", "2019 ohba et", "ohba et al. 2020", "al. 2020 zhang", "2020 zhang and", "and mao 2020 .
              htra2", "2020 .
              htra2 omi", "omi forms soluble", "forms soluble trimeric complexes", "soluble trimeric complexes in", "trimeric complexes in the", "complexes in the intermembrane", "the intermembrane space that", "intermembrane space that degrade", "space that degrade substrate", "that degrade substrate proteins", "substrate proteins notably", "proteins notably amyloid", "notably amyloid precursor proteins", "amyloid precursor proteins that", "precursor proteins that are", "proteins that are translocated", "that are translocated to", "are translocated to the", "translocated to the intermembrane", "to the intermembrane space", "space and inner membrane.", "and inner membrane. htra2", "inner membrane. htra2 released", "membrane. htra2 released from", "htra2 released from mitochondria", "released from mitochondria into", "from mitochondria into the", "mitochondria into the cytosol", "into the cytosol also", "the cytosol also participates", "cytosol also participates in", "also participates in regulating", "participates in regulating apoptosis", "regulating apoptosis reviewed", "apoptosis reviewed in", "reviewed in vande walle", "in vande walle et", "vande walle et al.", "walle et al. 2008", "et al. 2008 .
              mutations", "al. 2008 .
              mutations in", "2008 .
              mutations in mitochondrial", ".
              mutations in mitochondrial proteases", "in mitochondrial proteases cause", "mitochondrial proteases cause diseases", "cause diseases such", "diseases such as", "such as spastic paraplegia", "spastic paraplegia spg7", "spg7 ataxia", "parkinson's disease htra2", "htra2 that", "that typically have neurological", "typically have neurological symptoms", "have neurological symptoms among", "neurological symptoms among others", "among others reviewed", "others reviewed in", "reviewed in su et", "in su et al.", "su et al. 2019", "al. 2019 gomez", "2019 gomez fabra", "gomez fabra gala and", "fabra gala and vogtle", "gala and vogtle 2021", "and vogtle 2021 .", "mitochondrial proteases participate in proteostasis", "participate in proteostasis the", "in proteostasis the regulation", "proteostasis the regulation of", "the regulation of proteins to", "regulation of proteins to maintain", "of proteins to maintain a", "proteins to maintain a functional", "to maintain a functional proteome", "a functional proteome by", "functional proteome by degrading", "proteome by degrading unfolded", "by degrading unfolded unassembled", "unfolded unassembled and", "unassembled and oxidatively damaged", "oxidatively damaged proteins reviewed", "damaged proteins reviewed in", "proteins reviewed in ng", "reviewed in ng et al.", "in ng et al. 2021", "et al. 2021 song", "al. 2021 song et", "2021 song et al.", "song et al. 2021 .", "et al. 2021 . degradation", "al. 2021 . degradation of", "2021 . degradation of mitochondrial", ". degradation of mitochondrial proteins", "degradation of mitochondrial proteins by", "of mitochondrial proteins by proteases", "mitochondrial proteins by proteases also", "proteins by proteases also serves", "by proteases also serves to", "proteases also serves to regulate", "also serves to regulate transcription", "serves to regulate transcription by", "to regulate transcription by tfam", "transcription by tfam oxidative", "by tfam oxidative phosphorylation", "tfam oxidative phosphorylation by", "oxidative phosphorylation by electron carriers", "by electron carriers lipid", "electron carriers lipid translocation", "carriers lipid translocation by", "lipid translocation by prelid1 and", "translocation by prelid1 and stard7", "prelid1 and stard7 and", "and stard7 and mitochondrial", "stard7 and mitochondrial fission", "and mitochondrial fission and fusion", "mitochondrial fission and fusion by", "fission and fusion by opa1", "and fusion by opa1 and", "fusion by opa1 and oma1", "opa1 and oma1 reviewed", "and oma1 reviewed in", "oma1 reviewed in ahola", "reviewed in ahola et al.", "in ahola et al. 2019", "ahola et al. 2019 .", "et al. 2019 . because", "al. 2019 . because of", "2019 . because of the", ". because of the bacterial", "because of the bacterial origin", "of the bacterial origin of", "the bacterial origin of mitochondria", "origin of mitochondria they", "of mitochondria they contain", "mitochondria they contain a", "they contain a number of", "contain a number of bacterial", "a number of bacterial type", "number of bacterial type proteases", "bacterial type proteases including", "type proteases including lonp1", "proteases including lonp1 in", "including lonp1 in the matrix", "in the matrix clpp:clpx", "matrix clpp:clpx clpxp", "clpp:clpx clpxp in", "clpxp in the matrix", "in the matrix htra2", "matrix htra2 omi", "htra2 omi in", "omi in the intermembrane", "the intermembrane space afg3l2", "intermembrane space afg3l2 in", "space afg3l2 in the", "afg3l2 in the mitochondrial inner", "in the mitochondrial inner membrane", "the mitochondrial inner membrane and", "mitochondrial inner membrane and protruding", "inner membrane and protruding into", "membrane and protruding into the", "and protruding into the matrix", "into the matrix and", "the matrix and yme1l1", "matrix and yme1l1 in", "and yme1l1 in the mitochondrial", "yme1l1 in the mitochondrial inner", "and protruding into the intermembrane", "protruding into the intermembrane space", "the intermembrane space reviewed", "intermembrane space reviewed in", "space reviewed in deshwal", "reviewed in deshwal et al.", "in deshwal et al. 2020", "et al. 2020 szczepanowska", "al. 2020 szczepanowska and", "2020 szczepanowska and trifunovic", "szczepanowska and trifunovic 2022 .
              the", "and trifunovic 2022 .
              the hexameric", "trifunovic 2022 .
              the hexameric lonp1", "2022 .
              the hexameric lonp1 complex", "hexameric lonp1 complex which", "lonp1 complex which is", "complex which is homologous", "which is homologous to lon", "is homologous to lon proteases", "homologous to lon proteases of", "to lon proteases of eubacteria", "lon proteases of eubacteria such", "proteases of eubacteria such as", "of eubacteria such as e.", "eubacteria such as e. coli", "as e. coli binds", "e. coli binds substrate", "coli binds substrate proteins", "binds substrate proteins in the", "substrate proteins in the matrix", "proteins in the matrix and", "in the matrix and inner", "the matrix and inner membrane", "and inner membrane unfolds", "inner membrane unfolds them", "membrane unfolds them in", "unfolds them in an atp", "them in an atp dependent", "in an atp dependent mechanism", "atp dependent mechanism and", "dependent mechanism and degrades", "mechanism and degrades them", "and degrades them reviewed", "degrades them reviewed in", "them reviewed in gibellini", "reviewed in gibellini et al.", "in gibellini et al. 2020", "gibellini et al. 2020 .", "et al. 2020 . lonp1", "al. 2020 . lonp1 also", "2020 . lonp1 also acts", ". lonp1 also acts as", "lonp1 also acts as an", "also acts as an atp", "acts as an atp dependent", "as an atp dependent chaperone", "an atp dependent chaperone that", "atp dependent chaperone that is", "dependent chaperone that is independent", "chaperone that is independent of", "that is independent of its", "is independent of its protease", "independent of its protease function", "its protease function reviewed", "protease function reviewed in", "function reviewed in gibellini", "gibellini et al. 2020 .
              like", "et al. 2020 .
              like lonp1", "2020 .
              like lonp1 the", ".
              like lonp1 the clpxp", "lonp1 the clpxp complex", "the clpxp complex unfolds matrix", "clpxp complex unfolds matrix proteins", "complex unfolds matrix proteins in", "unfolds matrix proteins in an", "matrix proteins in an atp", "proteins in an atp dependent", "in an atp dependent reaction", "an atp dependent reaction and", "atp dependent reaction and degrades", "dependent reaction and degrades them", "and degrades them however", "them however the", "however the atpase/unfolding function", "the atpase/unfolding function and the", "atpase/unfolding function and the protease", "function and the protease function", "and the protease function are", "the protease function are performed", "protease function are performed by", "function are performed by separate", "are performed by separate subunits", "by separate subunits with", "separate subunits with clpx", "subunits with clpx hexamers", "with clpx hexamers unfolding substrate", "clpx hexamers unfolding substrate proteins", "hexamers unfolding substrate proteins and", "unfolding substrate proteins and translocating", "substrate proteins and translocating them", "proteins and translocating them to", "and translocating them to clpp", "translocating them to clpp tetradecamers", "them to clpp tetradecamers for", "to clpp tetradecamers for processive", "clpp tetradecamers for processive degradation", "for processive degradation reviewed", "processive degradation reviewed in", "degradation reviewed in mabanglo", "reviewed in mabanglo et al.", "in mabanglo et al. 2021", "et al. 2021 mabanglo", "al. 2021 mabanglo and", "2021 mabanglo and houry", "mabanglo and houry 2022 .
              afg3l2", "houry 2022 .
              afg3l2 m", "2022 .
              afg3l2 m aaa+", "m aaa+ forms either", "aaa+ forms either homohexamers", "forms either homohexamers or heterohexamers", "either homohexamers or heterohexamers with", "homohexamers or heterohexamers with its", "or heterohexamers with its paralog", "heterohexamers with its paralog spg7", "its paralog spg7 paraplegin", "spg7 paraplegin that", "paraplegin that are anchored", "that are anchored in the", "are anchored in the mitochondrial", "anchored in the mitochondrial inner", "mitochondrial inner membrane and protrude", "inner membrane and protrude into", "membrane and protrude into the", "and protrude into the matrix", "into the matrix reviewed", "the matrix reviewed in", "matrix reviewed in patron", "reviewed in patron et al.", "in patron et al. 2018", "et al. 2018 steele", "al. 2018 steele and", "2018 steele and glynn", "and glynn 2019 zhang", "glynn 2019 zhang and", "2019 zhang and mao", "zhang and mao 2020 .", "and mao 2020 . the", "mao 2020 . the substrate", "2020 . the substrate protein", ". the substrate protein enters", "the substrate protein enters the", "substrate protein enters the central", "protein enters the central channel", "enters the central channel formed", "the central channel formed by", "central channel formed by the", "channel formed by the atpase", "formed by the atpase domains", "by the atpase domains of", "the atpase domains of afg3l2", "atpase domains of afg3l2 and", "domains of afg3l2 and is", "of afg3l2 and is unfolded", "afg3l2 and is unfolded and", "and is unfolded and translocated", "is unfolded and translocated to", "unfolded and translocated to the", "and translocated to the pore", "translocated to the pore formed", "to the pore formed by", "the pore formed by the", "pore formed by the protease", "formed by the protease domains", "the protease domains where", "protease domains where it", "domains where it is", "it is degraded reviewed", "is degraded reviewed inzhang", "degraded reviewed inzhang and", "reviewed inzhang and mao 2020", "inzhang and mao 2020 .", "and mao 2020 .
              like", "mao 2020 .
              like afg3l2", ".
              like afg3l2 yme1l1", "afg3l2 yme1l1 yme1l", "yme1l1 yme1l i", "i aaa+ is a", "aaa+ is a homohexameric", "is a homohexameric complex that", "a homohexameric complex that is", "homohexameric complex that is anchored", "complex that is anchored in", "that is anchored in the", "is anchored in the mitochondrial", "mitochondrial inner membrane however", "membrane however yme1l1", "however yme1l1 protrudes into", "yme1l1 protrudes into the intermembrane", "protrudes into the intermembrane space", "into the intermembrane space where", "the intermembrane space where it", "intermembrane space where it unfolds", "space where it unfolds substrate", "where it unfolds substrate proteins", "it unfolds substrate proteins of", "unfolds substrate proteins of the", "substrate proteins of the intermembrane", "proteins of the intermembrane space", "of the intermembrane space and", "the intermembrane space and inner", "intermembrane space and inner membrane", "space and inner membrane in", "and inner membrane in an", "inner membrane in an atp", "membrane in an atp dependent", "atp dependent reaction and then", "dependent reaction and then degrades", "reaction and then degrades them", "then degrades them reviewed", "them reviewed in steele", "reviewed in steele and glynn", "in steele and glynn 2019", "and glynn 2019 ohba", "glynn 2019 ohba et", "2019 ohba et al.", "et al. 2020 zhang", "al. 2020 zhang and", "2020 zhang and mao", "zhang and mao 2020 .
              htra2", "mao 2020 .
              htra2 omi", ".
              htra2 omi forms", "omi forms soluble trimeric", "forms soluble trimeric complexes in", "soluble trimeric complexes in the", "trimeric complexes in the intermembrane", "complexes in the intermembrane space", "in the intermembrane space that", "the intermembrane space that degrade", "intermembrane space that degrade substrate", "space that degrade substrate proteins", "degrade substrate proteins notably", "substrate proteins notably amyloid", "proteins notably amyloid precursor", "notably amyloid precursor proteins that", "amyloid precursor proteins that are", "precursor proteins that are translocated", "proteins that are translocated to", "that are translocated to the", "are translocated to the intermembrane", "translocated to the intermembrane space", "to the intermembrane space and", "intermembrane space and inner membrane.", "space and inner membrane. htra2", "and inner membrane. htra2 released", "inner membrane. htra2 released from", "membrane. htra2 released from mitochondria", "htra2 released from mitochondria into", "released from mitochondria into the", "from mitochondria into the cytosol", "mitochondria into the cytosol also", "into the cytosol also participates", "the cytosol also participates in", "cytosol also participates in regulating", "also participates in regulating apoptosis", "in regulating apoptosis reviewed", "regulating apoptosis reviewed in", "apoptosis reviewed in vande", "reviewed in vande walle et", "in vande walle et al.", "vande walle et al. 2008", "walle et al. 2008 .
              mutations", "et al. 2008 .
              mutations in", "al. 2008 .
              mutations in mitochondrial", "2008 .
              mutations in mitochondrial proteases", ".
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infected", "interferon response in infected cells.", "response in infected cells. all", "in infected cells. all rsv", "infected cells. all rsv mrnas", "cells. all rsv mrnas undergo", "all rsv mrnas undergo 5'", "rsv mrnas undergo 5' capping", "mrnas undergo 5' capping and", "undergo 5' capping and 3'", "5' capping and 3' polyadenylation", "and 3' polyadenylation performed", "3' polyadenylation performed by", "polyadenylation performed by the", "performed by the viral rdrp.", "by the viral rdrp. for", "the viral rdrp. for review", "rdrp. for review please", "for review please refer", "review please refer to", "please refer to battles and", "refer to battles and mclellan", "to battles and mclellan 2019." ] }, { "record_id": "GLY_000594_1_2108", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9851151", "r hsa", "hsa 9851151", "r hsa 9851151" ] }, { "record_id": "GLY_000594_1_2108", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mdk and", "and ptn", "ptn in", "in alk", "alk signaling", "mdk and ptn", "and ptn in", "ptn in alk", "in alk signaling", "mdk and ptn in", "and ptn in alk", "ptn in alk signaling", "mdk and ptn in alk", "and ptn in alk signaling", "the cytokines", "cytokines pleiotrophin", "and midikine", "were initially", "initially proposed", "proposed to", "to act", "act as", "as ligands", "ligands for", "for alk", "stoica et", "et al", "reviewed in", "in wellstein", "wellstein et", "winkler et", "herradon and", "and perez", "perez garcia", "2014 .", ". binding", "binding of", "of ptn", "ptn or", "or mdk", "mdk to", "to alk", "alk either", "either in", "in cell", "cell free", "free assays", "assays or", "or in", "in intact", "intact cells", "cells was", "was shown", "shown to", "to stimulate", "stimulate signaling", "signaling through", "through irs", "plc and", "and pi3k", "pi3k and", "and to", "to support", "support neurite", "neurite outgrowth", "growth and", 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              within the", "two populations", "populations of", "of cells", "cells can", "can be", "be identified", "identified based", "based on", "on gene", "gene expression", "expression and", "and timing", "timing of", "of contribution", "contribution to", "the developing", "developing heart:", "heart: the", "first heart", "heart field", "forms the", "the initial", "initial heart", "heart tube", "tube and", "and contributes", "contributes to", "the systemic", "systemic ventricle", "the left", "left ventricle", "ventricle in", "in crocodilians", "and mammals", "the septum", "to a", "a lesser", "lesser extent", "the atria", "the second", "second heart", "extends the", "the poles", "poles of", "of the", "the heart", "heart and", "the outflow", "outflow tract", "the right", "right ventricle", "which is", "is responsible", "responsible for", "for pulmonary", "pulmonary circulation", "circulation and", "and distinguishes", "distinguishes crocodilians", "in meilhac", "meilhac and", "and buckingham", "buckingham 2018", "2018 .

              at", ".

              at about", "about 3", "3 weeks", "weeks gestation", "e8 in", "fhf cells", "migrate axially", "axially to", "midline and", "and fuse", "fuse to", "heart tube.", "tube. elongation", "elongation of", "tube leads", "leads to", "to rightward", "rightward looping", "looping and", "and eventual", "eventual formation", "of atria", "atria and", "and ventricles", "in desgrange", "desgrange et", "2018 .", ". fhf", "cells do", "do not", "not proliferate", "proliferate as", "as much", "much as", "as shf", "shf cells", "cells and", "and mostly", "mostly differentiate", "differentiate into", "into cardiomyocytes", "cardiomyocytes due", "due to", "the actions", "actions of", "of myocardial", "myocardial differentiation", "differentiation factors", "factors such", "such as", "as nkx2", "nkx2 5", "and hand1.", "hand1. shf", "cells are", "are initially", "initially located", "located in", "the posterior", "posterior region", "region of", "crescent then", "during formation", "become located", "located at", "at the", "the arterial", "arterial and", "and venous", "venous poles", "tube. shf", "cells proliferate", "proliferate more", "more than", "than fhf", "and can", "can differentiate", "differentiate to", "form cardiomyocytes", "endothelial cells", "smooth muscle", "muscle cells", "and fibroblasts.", "fibroblasts. a", "a reservoir", "reservoir of", "of shf", "shf progenitors", "progenitors located", "the core", "core of", "the pharyngeal", "pharyngeal mesoderm", "mesoderm continuously", "continuously contributes", "developing heart.", "heart. proliferating", "proliferating shf", "cells express", "express fgf8", "fgf8 and", "and fgf10", "fgf10 driven", "driven by", "by isl1", "isl1 and", "and tbx1.

              cardiac", "tbx1.

              cardiac progenitors", "progenitors are", "are regulated", "regulated by", "by a", "a distinct", "distinct set", "set of", "of transcription", "transcription factors", "factors and", "and mutations", "mutations in", "in these", "these factors", "and other", "other factors", "factors involved", "involved in", "in gene", "expression are", "are responsible", "for congenital", "congenital heart", "heart defects", "in diab", "diab et", "houyel and", "and meilhac", "meilhac 2021", "kodo et", "miyamoto et", "lescroart and", "and zaffran", "zaffran 2022", "wang et", "al. 2022", "2022 .", ". additionally", "combinations of", "of these", "these transcription", "factors are", "are now", "now being", "being used", "used to", "to reprogram", "reprogram fibroblasts", "fibroblasts and", "other cell", "cell types", "types into", "cardiomyocytes for", "for repairing", "repairing damaged", "damaged hearts", "in adams", "adams et", "garry et", "kim et", "thomas et", "zhu et", ". tbxt", "is expressed", "expressed early", "early in", "in developing", "developing mesoderm", "mesoderm and", "and is", "is activated", "activated by", "by wnt", "wnt signaling", "which maintains", "maintains proliferation", "proliferation and", "is subsequently", "subsequently downregulated", "downregulated during", "during differentiation.", "differentiation. activation", "activation of", "mesp1 expression", "expression by", "by tbxt", "tbxt and", "and eomes", "eomes occurs", "occurs early", "in gastrulation.", "gastrulation. mesp1", "mesp1 is", "in both", "both the", "the fhf", "fhf and", "the shf.", "shf. mesp1", "in turn", "directly activates", "activates two", "two key", "key regulators", "regulators of", "cardiac development:", "development: gata4", "gata4 and", "and nkx2", "the ortholog", "ortholog of", "of tinman", "tinman in", "in drosophila", "drosophila .", ". bone", "signaling originating", "originating from", "from bmps", "bmps secreted", "secreted by", "by underlying", "underlying endoderm", "endoderm also", "also enhances", "enhances expression", "of gata4", "apparently through", "through binding", "binding of", "of smad", "smad proteins", "proteins to", "the promoters", "promoters of", "nkx2 5.", "5. gata4", "5 proteins", "regulate each", "each other's", "other's expression", "and directly", "directly interact", "interact to", "to regulate", "regulate downstream", "downstream target", "target genes.", "genes. nkx2", "5 directly", "activates gata6", "gata6 throughout", "throughout the", "cardiac mesoderm.

              the", "mesoderm.

              the fhf", "fhf is", "is characterized", "characterized by", "by expression", "of tbx5", "tbx5 and", "and hcn4", "the shf", "shf is", "by transient", "transient expression", "of tbx1", "and six2.", "six2. in", "5 binds", "binds the", "the promoter", "promoter of", "the tbx5", "tbx5 gene", "gene and", "and activates", "activates transcription.", "transcription. tbx5", "activates expression", "of srf.", "srf. tbx5", "tbx5 protein", "protein interacts", "interacts directly", "directly with", "with nkx2", "5 and", "and gata4", "gata4 proteins", "to activate", "activate further", "further downstream", "downstream targets.", "targets. sonic", "sonic hedgehog", "from the", "pharyngeal endoderm", "endoderm and", "and wnt", "signaling maintain", "maintain proliferation", "proliferation of", "and lef1:ctnn1", "lef1:beta catenin", "catenin from", "from wnt", "directly activate", "activate isl1", "characteristic of", "and isl1", "isl1 then", "then activates", "of hand2", "also characteristic", "shf cells.", "gradients of bone", "of bone morphogenetic", "bone morphogenetic protein", "protein bmp", "wingless related integration", "related integration site", "site wnt", "and nodal promote", "nodal promote the", "promote the formation", "the formation of", "formation of cardiac", "of cardiac progenitors", "cardiac progenitors anteriolateral", "progenitors anteriolateral to", "anteriolateral to the", "to the primitive", "the primitive streak", "primitive streak during", "streak during gastrulation", "gastrulation reviewed", "reviewed in munoz", "in munoz chapuli", "munoz chapuli and", "chapuli and perez", "and perez pomares", "perez pomares 2010", "2010 cui", "cui et al.", "et al. 2018", "2018 prummel", "prummel et al.", "et al. 2020", "2020 witman", "witman et al.", "et al. 2019", "2019 miyamoto", "miyamoto e al.", "e al. 2021", "al. 2021 .", "2021 . eomesodermin", "eomesodermin eomes", "eomes and", "tbxt t", "t brachyury", "brachyury expressed", "expressed in the", "in the cardiac", "the cardiac mesoderm", "cardiac mesoderm activate", "mesoderm activate expression", "activate expression of", "expression of mesp1", "mesp1 a", "a master regulator", "master regulator of", "regulator of cardiogenesis", "of cardiogenesis and", "cardiogenesis and the", "and the first", "the first observed", "first observed marker", "observed marker of", "marker of cardiac", "of cardiac progenitors.", "cardiac progenitors. mesp1", "progenitors. mesp1 expressing", "mesp1 expressing cells", "expressing cells migrate", "cells migrate anteriorly", "migrate anteriorly towards", "anteriorly towards the", "towards the midline", "the midline to", "midline to form", "to form the", "form the cardiac", "the cardiac crescent", "cardiac crescent posterior", "crescent posterior to", "posterior to the", "to the head", "the head folds", "head folds at", "folds at about", "at about 2", "about 2 weeks", "2 weeks of", "weeks of gestation", "of gestation in", "gestation in humans", "humans e7.5", "e7.5 in mice", "in mice .

              within", "mice .

              within the", ".

              within the cardiac", "crescent two", "two populations of", "populations of cells", "of cells can", "cells can be", "can be identified", "be identified based", "identified based on", "based on gene", "on gene expression", "gene expression and", "expression and timing", "and timing of", "timing of contribution", "of contribution to", "contribution to the", "to the developing", "the developing heart:", "developing heart: the", "heart: the first", "the first heart", "first heart field", "field fhf", "fhf forms", "forms the initial", "the initial heart", "initial heart tube", "heart tube and", "tube and contributes", "and contributes to", "contributes to the", "to the systemic", "the systemic ventricle", "ventricle the", "the left ventricle", "left ventricle in", "ventricle in crocodilians", "crocodilians birds", "birds and", "septum and", "and to", "to a lesser", "a lesser extent", "extent the", "atria the", "the second heart", "second heart field", "field shf", "shf extends", "extends the poles", "the poles of", "poles of the", "of the heart", "the heart and", "heart and contributes", "to the atria", "the outflow tract", "tract the", "and the right", "the right ventricle", "ventricle which", "which is responsible", "is responsible for", "responsible for pulmonary", "for pulmonary circulation", "pulmonary circulation and", "circulation and distinguishes", "and distinguishes crocodilians", "mammals reviewed", "reviewed in meilhac", "in meilhac and", "meilhac and buckingham", "and buckingham 2018", "buckingham 2018 .

              at", "2018 .

              at about", ".

              at about 3", "about 3 weeks", "3 weeks gestation", "weeks gestation in", "humans e8", "e8 in mice", "fhf cells migrate", "cells migrate axially", "migrate axially to", "axially to the", "to the midline", "the midline and", "midline and fuse", "and fuse to", "fuse to form", "form the heart", "the heart tube.", "heart tube. elongation", "tube. elongation of", "elongation of the", "the heart tube", "heart tube leads", "tube leads to", "leads to rightward", "to rightward looping", "rightward looping and", "looping and eventual", "and eventual formation", "eventual formation of", "formation of atria", "of atria and", "atria and ventricles", "ventricles reviewed", "reviewed in desgrange", "in desgrange et", "desgrange et al.", "al. 2018 .", "2018 . fhf", ". fhf cells", "fhf cells do", "cells do not", "do not proliferate", "not proliferate as", "proliferate as much", "as much as", "much as shf", "as shf cells", "shf cells and", "cells and mostly", "and mostly differentiate", "mostly differentiate into", "differentiate into cardiomyocytes", "into cardiomyocytes due", "cardiomyocytes due to", "due to the", "to the actions", "the actions of", "actions of myocardial", "of myocardial differentiation", "myocardial differentiation factors", "differentiation factors such", "factors such as", "such as nkx2", "as nkx2 5", "5 gata4", "gata4 tbx5", "and hand1. shf", "hand1. shf cells", "shf cells are", "cells are initially", "are initially located", "initially located in", "located in the", "in the posterior", "the posterior region", "posterior region of", "region of the", "of the cardiac", "cardiac crescent then", "then during", "during formation of", "formation of the", "tube become", "become located at", "located at the", "at the arterial", "the arterial and", "arterial and venous", "and venous poles", "venous poles of", "heart tube. shf", "tube. shf cells", "shf cells proliferate", "cells proliferate more", "proliferate more than", "more than fhf", "than fhf cells", "fhf cells and", "cells and can", "and can differentiate", "can differentiate to", "differentiate to form", "to form cardiomyocytes", "cardiomyocytes endothelial", "cells smooth", "smooth muscle cells", "and fibroblasts. a", "fibroblasts. a reservoir", "a reservoir of", "reservoir of shf", "of shf progenitors", "shf progenitors located", "progenitors located at", "at the core", "the core of", "core of the", "of the pharyngeal", "the pharyngeal mesoderm", "pharyngeal mesoderm continuously", "mesoderm continuously contributes", "continuously contributes to", "the developing heart.", "developing heart. proliferating", "heart. proliferating shf", "proliferating shf cells", "shf cells express", "cells express fgf8", "express fgf8 and", "fgf8 and fgf10", "and fgf10 driven", "fgf10 driven by", "driven by isl1", "by isl1 and", "isl1 and tbx1.

              cardiac", "and tbx1.

              cardiac progenitors", "tbx1.

              cardiac progenitors are", "progenitors are regulated", "are regulated by", "regulated by a", "by a distinct", "a distinct set", "distinct set of", "set of transcription", "of transcription factors", "transcription factors and", "factors and mutations", "and mutations in", "mutations in these", "in these factors", "these factors and", "factors and other", "and other factors", "other factors involved", "factors involved in", "involved in gene", "in gene expression", "gene expression are", "expression are responsible", "are responsible for", "responsible for congenital", "for congenital heart", "congenital heart defects", "defects reviewed", "reviewed in diab", "in diab et", "diab et al.", "et al. 2021", "2021 houyel", "houyel and meilhac", "and meilhac 2021", "2021 kodo", "kodo et al.", "2021 miyamoto", "miyamoto et al.", "2021 lescroart", "lescroart and zaffran", "and zaffran 2022", "2022 wang", "wang et al.", "et al. 2022", "al. 2022 .", "2022 . additionally", "additionally combinations", "combinations of these", "of these transcription", "these transcription factors", "transcription factors are", "factors are now", "are now being", "now being used", "being used to", "used to reprogram", "to reprogram fibroblasts", "reprogram fibroblasts and", "fibroblasts and other", "and other cell", "other cell types", "cell types into", "types into cardiomyocytes", "into cardiomyocytes for", "cardiomyocytes for repairing", "for repairing damaged", "repairing damaged hearts", "hearts reviewed", "reviewed in adams", "in adams et", "adams et al.", "2021 garry", "garry et al.", "2021 kim", "kim et al.", "2022 thomas", "thomas et al.", "2022 zhu", "zhu et al.", "2022 . tbxt", "brachyury is", "is expressed early", "expressed early in", "early in developing", "in developing mesoderm", "developing mesoderm and", "mesoderm and is", "and is activated", "is activated by", "activated by wnt", "by wnt signaling", "signaling which", "which maintains proliferation", "maintains proliferation and", "proliferation and is", "and is subsequently", "is subsequently downregulated", "subsequently downregulated during", "downregulated during differentiation.", "during differentiation. activation", "differentiation. activation of", "activation of mesp1", "of mesp1 expression", "mesp1 expression by", "expression by tbxt", "by tbxt and", "tbxt and eomes", "and eomes occurs", "eomes occurs early", "occurs early in", "early in gastrulation.", "in gastrulation. mesp1", "gastrulation. mesp1 is", "mesp1 is expressed", "is expressed in", "expressed in both", "in both the", "both the fhf", "the fhf and", "fhf and the", "and the shf.", "the shf. mesp1", "mesp1 in", "turn directly", "directly activates two", "activates two key", "two key regulators", "key regulators of", "regulators of cardiac", "of cardiac development:", "cardiac development: gata4", "development: gata4 and", "gata4 and nkx2", "and nkx2 5", "5 nkx2.5", "nkx2.5 the", "the ortholog of", "ortholog of tinman", "of tinman in", "tinman in drosophila", "in drosophila .", "drosophila . bone", ". bone morphogenetic", "bmp signaling", "signaling originating from", "originating from bmps", "from bmps secreted", "bmps secreted by", "secreted by underlying", "by underlying endoderm", "underlying endoderm also", "endoderm also enhances", "also enhances expression", "enhances expression of", "expression of gata4", "of gata4 and", "5 apparently", "apparently through binding", "through binding of", "binding of smad", "of smad proteins", "smad proteins to", "proteins to the", "to the promoters", "the promoters of", "promoters of gata4", "and nkx2 5.", "nkx2 5. gata4", "5. gata4 and", "nkx2 5 proteins", "proteins in", "turn regulate", "regulate each other's", "each other's expression", "other's expression and", "expression and directly", "and directly interact", "directly interact to", "interact to regulate", "to regulate downstream", "regulate downstream target", "downstream target genes.", "target genes. nkx2", "genes. nkx2 5", "nkx2 5 directly", "5 directly activates", "directly activates gata6", "activates gata6 throughout", "gata6 throughout the", "throughout the cardiac", "the cardiac mesoderm.

              the", "cardiac mesoderm.

              the fhf", "mesoderm.

              the fhf is", "fhf is characterized", "is characterized by", "characterized by expression", "by expression of", "expression of tbx5", "of tbx5 and", "tbx5 and hcn4", "hcn4 the", "the shf is", "shf is characterized", "characterized by transient", "by transient expression", "transient expression of", "expression of tbx1", "tbx1 isl1", "isl1 fgf8", "fgf8 fgf10", "fgf10 and", "and six2. in", "six2. in the", "in the fhf", "fhf nkx2", "nkx2 5 binds", "5 binds the", "binds the promoter", "the promoter of", "promoter of the", "of the tbx5", "the tbx5 gene", "tbx5 gene and", "gene and activates", "and activates transcription.", "activates transcription. tbx5", "tbx5 in", "directly activates expression", "activates expression of", "expression of srf.", "of srf. tbx5", "srf. tbx5 protein", "tbx5 protein interacts", "protein interacts directly", "interacts directly with", "directly with nkx2", "with nkx2 5", "nkx2 5 and", "5 and gata4", "and gata4 proteins", "gata4 proteins to", "proteins to activate", "to activate further", "activate further downstream", "further downstream targets.", "downstream targets. sonic", "targets. sonic hedgehog", "hedgehog shh", "shh from", "from the pharyngeal", "the pharyngeal endoderm", "pharyngeal endoderm and", "endoderm and wnt", "and wnt signaling", "wnt signaling maintain", "signaling maintain proliferation", "maintain proliferation of", "proliferation of shf", "of shf cells", "cells in", "in the shf", "shf tbx1", "tbx1 gata4", "gata4 and lef1:ctnn1", "lef1:ctnn1 lef1:beta", "lef1:beta catenin from", "catenin from wnt", "from wnt signaling", "signaling directly", "directly activate isl1", "isl1 characteristic", "characteristic of shf", "and isl1 then", "isl1 then activates", "then activates expression", "expression of hand2", "hand2 dhand", "also characteristic of", "of shf cells.", "gradients of bone morphogenetic", "of bone morphogenetic protein", "morphogenetic protein bmp", "bmp wingless", "wingless related integration site", "integration site wnt", "wnt and", "and nodal promote the", "nodal promote the formation", "promote the formation of", "the formation of cardiac", "formation of cardiac progenitors", "of cardiac progenitors anteriolateral", "cardiac progenitors anteriolateral to", "progenitors anteriolateral to the", "anteriolateral to the primitive", "to the primitive streak", "the primitive streak during", "primitive streak during gastrulation", "during gastrulation reviewed", "gastrulation reviewed in", "reviewed in munoz chapuli", "in munoz chapuli and", "munoz chapuli and perez", "chapuli and perez pomares", "and perez pomares 2010", "pomares 2010 cui", "2010 cui et", "cui et al. 2018", "al. 2018 prummel", "2018 prummel et", "prummel et al. 2020", "al. 2020 witman", "2020 witman et", "witman et al. 2019", "al. 2019 miyamoto", "2019 miyamoto e", "miyamoto e al. 2021", "e al. 2021 .", "al. 2021 . eomesodermin", ". eomesodermin eomes", "eomes and tbxt", "and tbxt t", "brachyury expressed in", "expressed in the cardiac", "in the cardiac mesoderm", "the cardiac mesoderm activate", "cardiac mesoderm activate expression", "mesoderm activate expression of", "activate expression of mesp1", "of mesp1 a", "mesp1 a master", "a master regulator of", "master regulator of cardiogenesis", "regulator of cardiogenesis and", "of cardiogenesis and the", "cardiogenesis and the first", "and the first observed", "the first observed marker", "first observed marker of", "observed marker of cardiac", "marker of cardiac progenitors.", "of cardiac progenitors. mesp1", "cardiac progenitors. mesp1 expressing", "progenitors. mesp1 expressing cells", "mesp1 expressing cells migrate", "expressing cells migrate anteriorly", "cells migrate anteriorly towards", "migrate anteriorly towards the", "anteriorly towards the midline", "towards the midline to", "the midline to form", "midline to form the", "to form the cardiac", "form the cardiac crescent", "the cardiac crescent posterior", "cardiac crescent posterior to", "crescent posterior to the", "posterior to the head", "to the head folds", "the head folds at", "head folds at about", "folds at about 2", "at about 2 weeks", "about 2 weeks of", "2 weeks of gestation", "weeks of gestation in", "of gestation in humans", "in humans e7.5", "humans e7.5 in", "e7.5 in mice .

              within", "in mice .

              within the", "mice .

              within the cardiac", ".

              within the cardiac crescent", "cardiac crescent two", "crescent two populations", "two populations of cells", "populations of cells can", "of cells can be", "cells can be identified", "can be identified based", "be identified based on", "identified based on gene", "based on gene expression", "on gene expression and", "gene expression and timing", "expression and timing of", "and timing of contribution", "timing of contribution to", "of contribution to the", "contribution to the developing", "to the developing heart:", "the developing heart: the", "developing heart: the first", "heart: the first heart", "the first heart field", "heart field fhf", "fhf forms the", "forms the initial heart", "the initial heart tube", "initial heart tube and", "heart tube and contributes", "tube and contributes to", "and contributes to the", "contributes to the systemic", "to the systemic ventricle", "systemic ventricle the", "ventricle the left", "the left ventricle in", "left ventricle in crocodilians", "in crocodilians birds", "birds and mammals", "mammals the", "the septum and", "and to a", "to a lesser extent", "lesser extent the", "extent the atria", "the atria the", "atria the second", "the second heart field", "heart field shf", "shf extends the", "extends the poles of", "the poles of the", "poles of the heart", "of the heart and", "the heart and contributes", "heart and contributes to", "contributes to the atria", "atria the outflow", "outflow tract the", "tract the septum", "septum and the", "and the right ventricle", "right ventricle which", "ventricle which is", "which is responsible for", "is responsible for pulmonary", "responsible for pulmonary circulation", "for pulmonary circulation and", "pulmonary circulation and distinguishes", "circulation and distinguishes crocodilians", "distinguishes crocodilians birds", "and mammals reviewed", "mammals reviewed in", "reviewed in meilhac and", "in meilhac and buckingham", "meilhac and buckingham 2018", "and buckingham 2018 .

              at", "buckingham 2018 .

              at about", "2018 .

              at about 3", ".

              at about 3 weeks", "about 3 weeks gestation", "3 weeks gestation in", "weeks gestation in humans", "in humans e8", "humans e8 in", "mice fhf", "fhf cells migrate axially", "cells migrate axially to", "migrate axially to the", "axially to the midline", "to the midline and", "the midline and fuse", "midline and fuse to", "and fuse to form", "fuse to form the", "to form the heart", "form the heart tube.", "the heart tube. elongation", "heart tube. elongation of", "tube. elongation of the", "elongation of the heart", "of the heart tube", "the heart tube leads", "heart tube leads to", "tube leads to rightward", "leads to rightward looping", "to rightward looping and", "rightward looping and eventual", "looping and eventual formation", "and eventual formation of", "eventual formation of atria", "formation of atria and", "of atria and ventricles", "and ventricles reviewed", "ventricles reviewed in", "reviewed in desgrange et", "in desgrange et al.", "desgrange et al. 2018", "et al. 2018 .", "al. 2018 . fhf", "2018 . fhf cells", ". fhf cells do", "fhf cells do not", "cells do not proliferate", "do not proliferate as", "not proliferate as much", "proliferate as much as", "as much as shf", "much as shf cells", "as shf cells and", "shf cells and mostly", "cells and mostly differentiate", "and mostly differentiate into", "mostly differentiate into cardiomyocytes", "differentiate into cardiomyocytes due", "into cardiomyocytes due to", "cardiomyocytes due to the", "due to the actions", "to the actions of", "the actions of myocardial", "actions of myocardial differentiation", "of myocardial differentiation factors", "myocardial differentiation factors such", "differentiation factors such as", "factors such as nkx2", "such as nkx2 5", "nkx2 5 gata4", "tbx5 and hand1.", "and hand1. shf cells", "hand1. shf cells are", "shf cells are initially", "cells are initially located", "are initially located in", "initially located in the", "located in the posterior", "in the posterior region", "the posterior region of", "posterior region of the", "region of the cardiac", "of the cardiac crescent", "the cardiac crescent then", "crescent then during", "then during formation", "during formation of the", "formation of the heart", "heart tube become", "tube become located", "become located at the", "located at the arterial", "at the arterial and", "the arterial and venous", "arterial and venous poles", "and venous poles of", "venous poles of the", "of the heart tube.", "the heart tube. shf", "heart tube. shf cells", "tube. shf cells proliferate", "shf cells proliferate more", "cells proliferate more than", "proliferate more than fhf", "more than fhf cells", "than fhf cells and", "fhf cells and can", "cells and can differentiate", "and can differentiate to", "can differentiate to form", "differentiate to form cardiomyocytes", "form cardiomyocytes endothelial", "cardiomyocytes endothelial cells", "endothelial cells smooth", "cells smooth muscle", "muscle cells and", "cells and fibroblasts.", "and fibroblasts. a reservoir", "fibroblasts. a reservoir of", "a reservoir of shf", "reservoir of shf progenitors", "of shf progenitors located", "shf progenitors located at", "progenitors located at the", "located at the core", "at the core of", "the core of the", "core of the pharyngeal", "of the pharyngeal mesoderm", "the pharyngeal mesoderm continuously", "pharyngeal mesoderm continuously contributes", "mesoderm continuously contributes to", "continuously contributes to the", "contributes to the developing", "to the developing heart.", "the developing heart. proliferating", "developing heart. proliferating shf", "heart. proliferating shf cells", "proliferating shf cells express", "shf cells express fgf8", "cells express fgf8 and", "express fgf8 and fgf10", "fgf8 and fgf10 driven", "and fgf10 driven by", "fgf10 driven by isl1", "driven by isl1 and", "by isl1 and tbx1.

              cardiac", "isl1 and tbx1.

              cardiac progenitors", "and tbx1.

              cardiac progenitors are", "tbx1.

              cardiac progenitors are regulated", "progenitors are regulated by", "are regulated by a", "regulated by a distinct", "by a distinct set", "a distinct set of", "distinct set of transcription", "set of transcription factors", "of transcription factors and", "transcription factors and mutations", "factors and mutations in", "and mutations in these", "mutations in these factors", "in these factors and", "these factors and other", "factors and other factors", "and other factors involved", "other factors involved in", "factors involved in gene", "involved in gene expression", "in gene expression are", "gene expression are responsible", "expression are responsible for", "are responsible for congenital", "responsible for congenital heart", "for congenital heart defects", "heart defects reviewed", "defects reviewed in", "reviewed in diab et", "in diab et al.", "diab et al. 2021", "al. 2021 houyel", "2021 houyel and", "houyel and meilhac 2021", "meilhac 2021 kodo", "2021 kodo et", "kodo et al. 2021", "al. 2021 miyamoto", "2021 miyamoto et", "miyamoto et al. 2021", "al. 2021 lescroart", "2021 lescroart and", "lescroart and zaffran 2022", "zaffran 2022 wang", "2022 wang et", "wang et al. 2022", "et al. 2022 .", "al. 2022 . additionally", ". additionally combinations", "additionally combinations of", "combinations of these transcription", "of these transcription factors", "these transcription factors are", "transcription factors are now", "factors are now being", "are now being used", "now being used to", "being used to reprogram", "used to reprogram fibroblasts", "to reprogram fibroblasts and", "reprogram fibroblasts and other", "fibroblasts and other cell", "and other cell types", "other cell types into", "cell types into cardiomyocytes", "types into cardiomyocytes for", "into cardiomyocytes for repairing", "cardiomyocytes for repairing damaged", "for repairing damaged hearts", "damaged hearts reviewed", "hearts reviewed in", "reviewed in adams et", "in adams et al.", "adams et al. 2021", "al. 2021 garry", "2021 garry et", "garry et al. 2021", "al. 2021 kim", "2021 kim et", "kim et al. 2022", "al. 2022 thomas", "2022 thomas et", "thomas et al. 2022", "al. 2022 zhu", "2022 zhu et", "zhu et al. 2022", "al. 2022 . tbxt", ". tbxt t", "brachyury is expressed", "is expressed early in", "expressed early in developing", "early in developing mesoderm", "in developing mesoderm and", "developing mesoderm and is", "mesoderm and is activated", "and is activated by", "is activated by wnt", "activated by wnt signaling", "wnt signaling which", "signaling which maintains", "which maintains proliferation and", "maintains proliferation and is", "proliferation and is subsequently", "and is subsequently downregulated", "is subsequently downregulated during", "subsequently downregulated during differentiation.", "downregulated during differentiation. activation", "during differentiation. activation of", "differentiation. activation of mesp1", "activation of mesp1 expression", "of mesp1 expression by", "mesp1 expression by tbxt", "expression by tbxt and", "by tbxt and eomes", "tbxt and eomes occurs", "and eomes occurs early", "eomes occurs early in", "occurs early in gastrulation.", "early in gastrulation. mesp1", "in gastrulation. mesp1 is", "gastrulation. mesp1 is expressed", "mesp1 is expressed in", "is expressed in both", "expressed in both the", "in both the fhf", "both the fhf and", "the fhf and the", "fhf and the shf.", "and the shf. mesp1", "shf. mesp1 in", "mesp1 in turn", "in turn directly", "turn directly activates", "directly activates two key", "activates two key regulators", "two key regulators of", "key regulators of cardiac", "regulators of cardiac development:", "of cardiac development: gata4", "cardiac development: gata4 and", "development: gata4 and nkx2", "gata4 and nkx2 5", "nkx2 5 nkx2.5", "nkx2.5 the ortholog", "the ortholog of tinman", "ortholog of tinman in", "of tinman in drosophila", "tinman in drosophila .", "in drosophila . bone", "drosophila . bone morphogenetic", ". bone morphogenetic protein", "bmp signaling originating", "signaling originating from bmps", "originating from bmps secreted", "from bmps secreted by", "bmps secreted by underlying", "secreted by underlying endoderm", "by underlying endoderm also", "underlying endoderm also enhances", "endoderm also enhances expression", "also enhances expression of", "enhances expression of gata4", "expression of gata4 and", "of gata4 and nkx2", "nkx2 5 apparently", "5 apparently through", "apparently through binding of", "through binding of smad", "binding of smad proteins", "of smad proteins to", "smad proteins to the", "proteins to the promoters", "to the promoters of", "the promoters of gata4", "promoters of gata4 and", "gata4 and nkx2 5.", "and nkx2 5. gata4", "nkx2 5. gata4 and", "5. gata4 and nkx2", "and nkx2 5 proteins", "5 proteins in", "proteins in turn", "in turn regulate", "turn regulate each", "regulate each other's expression", "each other's expression and", "other's expression and directly", "expression and directly interact", "and directly interact to", "directly interact to regulate", "interact to regulate downstream", "to regulate downstream target", "regulate downstream target genes.", "downstream target genes. nkx2", "target genes. nkx2 5", "genes. nkx2 5 directly", "nkx2 5 directly activates", "5 directly activates gata6", "directly activates gata6 throughout", "activates gata6 throughout the", "gata6 throughout the cardiac", "throughout the cardiac mesoderm.

              the", "the cardiac mesoderm.

              the fhf", "cardiac mesoderm.

              the fhf is", "mesoderm.

              the fhf is characterized", "fhf is characterized by", "is characterized by expression", "characterized by expression of", "by expression of tbx5", "expression of tbx5 and", "of tbx5 and hcn4", "and hcn4 the", "hcn4 the shf", "the shf is characterized", "shf is characterized by", "is characterized by transient", "characterized by transient expression", "by transient expression of", "transient expression of tbx1", "of tbx1 isl1", "fgf10 and six2.", "and six2. in the", "six2. in the fhf", "the fhf nkx2", "fhf nkx2 5", "nkx2 5 binds the", "5 binds the promoter", "binds the promoter of", "the promoter of the", "promoter of the tbx5", "of the tbx5 gene", "the tbx5 gene and", "tbx5 gene and activates", "gene and activates transcription.", "and activates transcription. tbx5", "transcription. tbx5 in", "tbx5 in turn", "directly activates expression of", "activates expression of srf.", "expression of srf. tbx5", "of srf. tbx5 protein", "srf. tbx5 protein interacts", "tbx5 protein interacts directly", "protein interacts directly with", "interacts directly with nkx2", "directly with nkx2 5", "with nkx2 5 and", "nkx2 5 and gata4", "5 and gata4 proteins", "and gata4 proteins to", "gata4 proteins to activate", "proteins to activate further", "to activate further downstream", "activate further downstream targets.", "further downstream targets. sonic", "downstream targets. sonic hedgehog", "sonic hedgehog shh", "shh from the", "from the pharyngeal endoderm", "the pharyngeal endoderm and", "pharyngeal endoderm and wnt", "endoderm and wnt signaling", "and wnt signaling maintain", "wnt signaling maintain proliferation", "signaling maintain proliferation of", "maintain proliferation of shf", "proliferation of shf cells", "shf cells in", "cells in the", "the shf tbx1", "tbx1 gata4 and", "and lef1:ctnn1 lef1:beta", "lef1:ctnn1 lef1:beta catenin", "lef1:beta catenin from wnt", "catenin from wnt signaling", "wnt signaling directly", "signaling directly activate", "activate isl1 characteristic", "isl1 characteristic of", "characteristic of shf cells", "cells and isl1", "and isl1 then activates", "isl1 then activates expression", "then activates expression of", "activates expression of hand2", "of hand2 dhand", "dhand also", "also characteristic of shf", "characteristic of shf cells.", "gradients of bone morphogenetic protein", "bone morphogenetic protein bmp", "bmp wingless related", "related integration site wnt", "wnt and nodal", "and nodal promote the formation", "nodal promote the formation of", "promote the formation of cardiac", "the formation of cardiac progenitors", "formation of cardiac progenitors anteriolateral", "of cardiac progenitors anteriolateral to", "cardiac progenitors anteriolateral to the", "progenitors anteriolateral to the primitive", "anteriolateral to the primitive streak", "to the primitive streak during", "the primitive streak during gastrulation", "streak during gastrulation reviewed", "during gastrulation reviewed in", "gastrulation reviewed in munoz", "reviewed in munoz chapuli and", "in munoz chapuli and perez", "munoz chapuli and perez pomares", "chapuli and perez pomares 2010", "perez pomares 2010 cui", "pomares 2010 cui et", "2010 cui et al.", "et al. 2018 prummel", "al. 2018 prummel et", "2018 prummel et al.", "et al. 2020 witman", "al. 2020 witman et", "2020 witman et al.", "et al. 2019 miyamoto", "al. 2019 miyamoto e", "2019 miyamoto e al.", "miyamoto e al. 2021 .", "e al. 2021 . eomesodermin", "2021 . eomesodermin eomes", "eomesodermin eomes and", "tbxt t brachyury", "t brachyury expressed", "brachyury expressed in the", "expressed in the cardiac mesoderm", "in the cardiac mesoderm activate", "the cardiac mesoderm activate expression", "cardiac mesoderm activate expression of", "mesoderm activate expression of mesp1", "expression of mesp1 a", "of mesp1 a master", "mesp1 a master regulator", "a master regulator of cardiogenesis", "master regulator of cardiogenesis and", "regulator of cardiogenesis and the", "of cardiogenesis and the first", "cardiogenesis and the first observed", "and the first observed marker", "the first observed marker of", "first observed marker of cardiac", "observed marker of cardiac progenitors.", "marker of cardiac progenitors. mesp1", "of cardiac progenitors. mesp1 expressing", "cardiac progenitors. mesp1 expressing cells", "progenitors. mesp1 expressing cells migrate", "mesp1 expressing cells migrate anteriorly", "expressing cells migrate anteriorly towards", "cells migrate anteriorly towards the", "migrate anteriorly towards the midline", "anteriorly towards the midline to", "towards the midline to form", "the midline to form the", "midline to form the cardiac", "to form the cardiac crescent", "form the cardiac crescent posterior", "the cardiac crescent posterior to", "cardiac crescent posterior to the", "crescent posterior to the head", "posterior to the head folds", "to the head folds at", "the head folds at about", "head folds at about 2", "folds at about 2 weeks", "at about 2 weeks of", "about 2 weeks of gestation", "2 weeks of gestation in", "weeks of gestation in humans", "gestation in humans e7.5", "in humans e7.5 in", "humans e7.5 in mice", "e7.5 in mice .

              within the", "in mice .

              within the cardiac", "mice .

              within the cardiac crescent", "the cardiac crescent two", "cardiac crescent two populations", "crescent two populations of", "two populations of cells can", "populations of cells can be", "of cells can be identified", "cells can be identified based", "can be identified based on", "be identified based on gene", "identified based on gene expression", "based on gene expression and", "on gene expression and timing", "gene expression and timing of", "expression and timing of contribution", "and timing of contribution to", "timing of contribution to the", "of contribution to the developing", "contribution to the developing heart:", "to the developing heart: the", "the developing heart: the first", "developing heart: the first heart", "heart: the first heart field", "first heart field fhf", "field fhf forms", "fhf forms the initial", "forms the initial heart tube", "the initial heart tube and", "initial heart tube and contributes", "heart tube and contributes to", "tube and contributes to the", "and contributes to the systemic", "contributes to the systemic ventricle", "the systemic ventricle the", "systemic ventricle the left", "ventricle the left ventricle", "the left ventricle in crocodilians", "ventricle in crocodilians birds", "crocodilians birds and", "and mammals the", "mammals the septum", "septum and to", "and to a lesser", "a lesser extent the", "lesser extent the atria", "the atria the second", "atria the second heart", "second heart field shf", "field shf extends", "shf extends the poles", "extends the poles of the", "the poles of the heart", "poles of the heart and", "of the heart and contributes", "the heart and contributes to", "heart and contributes to the", "and contributes to the atria", "to the atria the", "the atria the outflow", "atria the outflow tract", "the outflow tract the", "outflow tract the septum", "the septum and the", "septum and the right", "the right ventricle which", "right ventricle which is", "ventricle which is responsible", "which is responsible for pulmonary", "is responsible for pulmonary circulation", "responsible for pulmonary circulation and", "for pulmonary circulation and distinguishes", "pulmonary circulation and distinguishes crocodilians", "and distinguishes crocodilians birds", "and mammals reviewed in", "mammals reviewed in meilhac", "reviewed in meilhac and buckingham", "in meilhac and buckingham 2018", "meilhac and buckingham 2018 .

              at", "and buckingham 2018 .

              at about", "buckingham 2018 .

              at about 3", "2018 .

              at about 3 weeks", ".

              at about 3 weeks gestation", "about 3 weeks gestation in", "3 weeks gestation in humans", "gestation in humans e8", "in humans e8 in", "humans e8 in mice", "in mice fhf", "mice fhf cells", "fhf cells migrate axially to", "cells migrate axially to the", "migrate axially to the midline", "axially to the midline and", "to the midline and fuse", "the midline and fuse to", "midline and fuse to form", "and fuse to form the", "fuse to form the heart", "to form the heart tube.", "form the heart tube. elongation", "the heart tube. elongation of", "heart tube. elongation of the", "tube. elongation of the heart", "elongation of the heart tube", "of the heart tube leads", "the heart tube leads to", "heart tube leads to rightward", "tube leads to rightward looping", "leads to rightward looping and", "to rightward looping and eventual", "rightward looping and eventual formation", "looping and eventual formation of", "and eventual formation of atria", "eventual formation of atria and", "formation of atria and ventricles", "atria and ventricles reviewed", "and ventricles reviewed in", "ventricles reviewed in desgrange", "reviewed in desgrange et al.", "in desgrange et al. 2018", "desgrange et al. 2018 .", "et al. 2018 . fhf", "al. 2018 . fhf cells", "2018 . fhf cells do", ". fhf cells do not", "fhf cells do not proliferate", "cells do not proliferate as", "do not proliferate as much", "not proliferate as much as", "proliferate as much as shf", "as much as shf cells", "much as shf cells and", "as shf cells and mostly", "shf cells and mostly differentiate", "cells and mostly differentiate into", "and mostly differentiate into cardiomyocytes", "mostly differentiate into cardiomyocytes due", "differentiate into cardiomyocytes due to", "into cardiomyocytes due to the", "cardiomyocytes due to the actions", "due to the actions of", "to the actions of myocardial", "the actions of myocardial differentiation", "actions of myocardial differentiation factors", "of myocardial differentiation factors such", "myocardial differentiation factors such as", "differentiation factors such as nkx2", "factors such as nkx2 5", "as nkx2 5 gata4", "5 gata4 tbx5", "gata4 tbx5 and", "tbx5 and hand1. shf", "and hand1. shf cells are", "hand1. shf cells are initially", "shf cells are initially located", "cells are initially located in", "are initially located in the", "initially located in the posterior", "located in the posterior region", "in the posterior region of", "the posterior region of the", "posterior region of the cardiac", "region of the cardiac crescent", "of the cardiac crescent then", "cardiac crescent then during", "crescent then during formation", "then during formation of", "during formation of the heart", "formation of the heart tube", "the heart tube become", "heart tube become located", "tube become located at", "become located at the arterial", "located at the arterial and", "at the arterial and venous", "the arterial and venous poles", "arterial and venous poles of", "and venous poles of the", "venous poles of the heart", "poles of the heart tube.", "of the heart tube. shf", "the heart tube. shf cells", "heart tube. shf cells proliferate", "tube. shf cells proliferate more", "shf cells proliferate more than", "cells proliferate more than fhf", "proliferate more than fhf cells", "more than fhf cells and", "than fhf cells and can", "fhf cells and can differentiate", "cells and can differentiate to", "and can differentiate to form", "can differentiate to form cardiomyocytes", "to form cardiomyocytes endothelial", "form cardiomyocytes endothelial cells", "endothelial cells smooth muscle", "cells smooth muscle cells", "smooth muscle cells and", "muscle cells and fibroblasts.", "cells and fibroblasts. a", "and fibroblasts. a reservoir of", "fibroblasts. a reservoir of shf", "a reservoir of shf progenitors", "reservoir of shf progenitors located", "of shf progenitors located at", "shf progenitors located at the", "progenitors located at the core", "located at the core of", "at the core of the", "the core of the pharyngeal", "core of the pharyngeal mesoderm", "of the pharyngeal mesoderm continuously", "the pharyngeal mesoderm continuously contributes", "pharyngeal mesoderm continuously contributes to", "mesoderm continuously contributes to the", "continuously contributes to the developing", "contributes to the developing heart.", "to the developing heart. proliferating", "the developing heart. proliferating shf", "developing heart. proliferating shf cells", "heart. proliferating shf cells express", "proliferating shf cells express fgf8", "shf cells express fgf8 and", "cells express fgf8 and fgf10", "express fgf8 and fgf10 driven", "fgf8 and fgf10 driven by", "and fgf10 driven by isl1", "fgf10 driven by isl1 and", "driven by isl1 and tbx1.

              cardiac", "by isl1 and tbx1.

              cardiac progenitors", "isl1 and tbx1.

              cardiac progenitors are", "and tbx1.

              cardiac progenitors are regulated", "tbx1.

              cardiac progenitors are regulated by", "progenitors are regulated by a", "are regulated by a distinct", "regulated by a distinct set", "by a distinct set of", "a distinct set of transcription", "distinct set of transcription factors", "set of transcription factors and", "of transcription factors and mutations", "transcription factors and mutations in", "factors and mutations in these", "and mutations in these factors", "mutations in these factors and", "in these factors and other", "these factors and other factors", "factors and other factors involved", "and other factors involved in", "other factors involved in gene", "factors involved in gene expression", "involved in gene expression are", "in gene expression are responsible", "gene expression are responsible for", "expression are responsible for congenital", "are responsible for congenital heart", "responsible for congenital heart defects", "congenital heart defects reviewed", "heart defects reviewed in", "defects reviewed in diab", "reviewed in diab et al.", "in diab et al. 2021", "et al. 2021 houyel", "al. 2021 houyel and", "2021 houyel and meilhac", "and meilhac 2021 kodo", "meilhac 2021 kodo et", "2021 kodo et al.", "et al. 2021 miyamoto", "al. 2021 miyamoto et", "2021 miyamoto et al.", "et al. 2021 lescroart", "al. 2021 lescroart and", "2021 lescroart and zaffran", "and zaffran 2022 wang", "zaffran 2022 wang et", "2022 wang et al.", "wang et al. 2022 .", "et al. 2022 . additionally", "2022 . additionally combinations", ". additionally combinations of", "additionally combinations of these", "combinations of these transcription factors", "of these transcription factors are", "these transcription factors are now", "transcription factors are now being", "factors are now being used", "are now being used to", "now being used to reprogram", "being used to reprogram fibroblasts", "used to reprogram fibroblasts and", "to reprogram fibroblasts and other", "reprogram fibroblasts and other cell", "fibroblasts and other cell types", "and other cell types into", "other cell types into cardiomyocytes", "cell types into cardiomyocytes for", "types into cardiomyocytes for repairing", "into cardiomyocytes for repairing damaged", "cardiomyocytes for repairing damaged hearts", "repairing damaged hearts reviewed", "damaged hearts reviewed in", "hearts reviewed in adams", "reviewed in adams et al.", "in adams et al. 2021", "et al. 2021 garry", "al. 2021 garry et", "2021 garry et al.", "et al. 2021 kim", "al. 2021 kim et", "2021 kim et al.", "et al. 2022 thomas", "al. 2022 thomas et", "2022 thomas et al.", "et al. 2022 zhu", "al. 2022 zhu et", "2022 zhu et al.", "zhu et al. 2022 .", "et al. 2022 . tbxt", "2022 . tbxt t", "t brachyury is", "brachyury is expressed early", "is expressed early in developing", "expressed early in developing mesoderm", "early in developing mesoderm and", "in developing mesoderm and is", "developing mesoderm and is activated", "mesoderm and is activated by", "and is activated by wnt", "is activated by wnt signaling", "by wnt signaling which", "wnt signaling which maintains", "signaling which maintains proliferation", "which maintains proliferation and is", "maintains proliferation and is subsequently", "proliferation and is subsequently downregulated", "and is subsequently downregulated during", "is subsequently downregulated during differentiation.", "subsequently downregulated during differentiation. activation", "downregulated during differentiation. activation of", "during differentiation. activation of mesp1", "differentiation. activation of mesp1 expression", "activation of mesp1 expression by", "of mesp1 expression by tbxt", "mesp1 expression by tbxt and", "expression by tbxt and eomes", "by tbxt and eomes occurs", "tbxt and eomes occurs early", "and eomes occurs early in", "eomes occurs early in gastrulation.", "occurs early in gastrulation. mesp1", "early in gastrulation. mesp1 is", "in gastrulation. mesp1 is expressed", "gastrulation. mesp1 is expressed in", "mesp1 is expressed in both", "is expressed in both the", "expressed in both the fhf", "in both the fhf and", "both the fhf and the", "the fhf and the shf.", "fhf and the shf. mesp1", "the shf. mesp1 in", "shf. mesp1 in turn", "in turn directly activates", "turn directly activates two", "directly activates two key regulators", "activates two key regulators of", "two key regulators of cardiac", "key regulators of cardiac development:", "regulators of cardiac development: gata4", "of cardiac development: gata4 and", "cardiac development: gata4 and nkx2", "development: gata4 and nkx2 5", "and nkx2 5 nkx2.5", "5 nkx2.5 the", "nkx2.5 the ortholog of", "the ortholog of tinman in", "ortholog of tinman in drosophila", "of tinman in drosophila .", "tinman in drosophila . bone", "in drosophila . bone morphogenetic", "drosophila . bone morphogenetic protein", "protein bmp signaling", "bmp signaling originating from", "signaling originating from bmps secreted", "originating from bmps secreted by", "from bmps secreted by underlying", "bmps secreted by underlying endoderm", "secreted by underlying endoderm also", "by underlying endoderm also enhances", "underlying endoderm also enhances expression", "endoderm also enhances expression of", "also enhances expression of gata4", "enhances expression of gata4 and", "expression of gata4 and nkx2", "of gata4 and nkx2 5", "and nkx2 5 apparently", "nkx2 5 apparently through", "5 apparently through binding", "apparently through binding of smad", "through binding of smad proteins", "binding of smad proteins to", "of smad proteins to the", "smad proteins to the promoters", "proteins to the promoters of", "to the promoters of gata4", "the promoters of gata4 and", "promoters of gata4 and nkx2", "of gata4 and nkx2 5.", "gata4 and nkx2 5. gata4", "and nkx2 5. gata4 and", "nkx2 5. gata4 and nkx2", "5. gata4 and nkx2 5", "gata4 and nkx2 5 proteins", "nkx2 5 proteins in", "5 proteins in turn", "in turn regulate each", "turn regulate each other's", "regulate each other's expression and", "each other's expression and directly", "other's expression and directly interact", "expression and directly interact to", "and directly interact to regulate", "directly interact to regulate downstream", "interact to regulate downstream target", "to regulate downstream target genes.", "regulate downstream target genes. nkx2", "downstream target genes. nkx2 5", "target genes. nkx2 5 directly", "genes. nkx2 5 directly activates", "nkx2 5 directly activates gata6", "5 directly activates gata6 throughout", "directly activates gata6 throughout the", "activates gata6 throughout the cardiac", "gata6 throughout the cardiac mesoderm.

              the", "throughout the cardiac mesoderm.

              the fhf", "the cardiac mesoderm.

              the fhf is", "cardiac mesoderm.

              the fhf is characterized", "mesoderm.

              the fhf is characterized by", "fhf is characterized by expression", "is characterized by expression of", "characterized by expression of tbx5", "by expression of tbx5 and", "expression of tbx5 and hcn4", "tbx5 and hcn4 the", "and hcn4 the shf", "hcn4 the shf is", "the shf is characterized by", "shf is characterized by transient", "is characterized by transient expression", "characterized by transient expression of", "by transient expression of tbx1", "expression of tbx1 isl1", "tbx1 isl1 fgf8", "isl1 fgf8 fgf10", "fgf8 fgf10 and", "fgf10 and six2. in", "and six2. in the fhf", "in the fhf nkx2", "the fhf nkx2 5", "fhf nkx2 5 binds", "nkx2 5 binds the promoter", "5 binds the promoter of", "binds the promoter of the", "the promoter of the tbx5", "promoter of the tbx5 gene", "of the tbx5 gene and", "the tbx5 gene and activates", "tbx5 gene and activates transcription.", "gene and activates transcription. tbx5", "activates transcription. tbx5 in", "transcription. tbx5 in turn", "turn directly activates expression", "directly activates expression of srf.", "activates expression of srf. tbx5", "expression of srf. tbx5 protein", "of srf. tbx5 protein interacts", "srf. tbx5 protein interacts directly", "tbx5 protein interacts directly with", "protein interacts directly with nkx2", "interacts directly with nkx2 5", "directly with nkx2 5 and", "with nkx2 5 and gata4", "nkx2 5 and gata4 proteins", "5 and gata4 proteins to", "and gata4 proteins to activate", "gata4 proteins to activate further", "proteins to activate further downstream", "to activate further downstream targets.", "activate further downstream targets. sonic", "further downstream targets. sonic hedgehog", "targets. sonic hedgehog shh", "hedgehog shh from", "shh from the pharyngeal", "from the pharyngeal endoderm and", "the pharyngeal endoderm and wnt", "pharyngeal endoderm and wnt signaling", "endoderm and wnt signaling maintain", "and wnt signaling maintain proliferation", "wnt signaling 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              cdh11", ".

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              through", "2018 .

              through its", ".

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              cdh11", "2018 .

              cdh11 through", ".

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              through", "al. 2018 .

              through its", "2018 .

              through its extracellular", ".

              through its extracellular region", "extracellular region cdh11", "region cdh11 binds", "cdh11 binds to the", "binds to the c", "to the c terminal", "the c terminal fragment", "c terminal fragment of", "terminal fragment of angptl4", "of angptl4 angiopoietin", "angptl4 angiopoietin like", "4 commonly", "commonly known as cangptl4", "as cangptl4 which", "cangptl4 which is", "is implicated in the", "implicated in the regulation", "in the regulation of", "the regulation of wound", "regulation of wound healing.", "of wound healing. the", "wound healing. the variant", "healing. the variant isoform", "the variant isoform of", "variant isoform of cdh11", "of cdh11 cdh11v", "cdh11v an", "an 85 kda membrane", "85 kda membrane bound", "membrane bound protein", "bound protein produced", "protein produced as a", "produced as a result", "as a result of", "a result of alternative", "result of alternative splicing", "alternative splicing kawaguchi", "splicing kawaguchi et", "kawaguchi et al. 1999", "1999 can", "can compete with the", "compete with the canonical", "with the canonical cdh11", "the canonical cdh11 for", "canonical cdh11 for cangptl4", "cdh11 for cangptl4 binding", "cangptl4 binding teo", "binding teo et", "teo et al. 2017", "et al. 2017 .", "other classical cadherins cdh11", "classical cadherins cdh11 associates", "cadherins cdh11 associates with", "cdh11 associates with several catenin", "associates with several catenin proteins", "with several catenin proteins through", "several catenin proteins through its", "catenin proteins through its intracellular", "proteins through its intracellular domain", "its intracellular domain which", "intracellular domain which is", "domain which is thought", "which is thought to play", "is thought to play a", "thought to play a role", "to play a role in", "play a role in the", "a role in the establishment", "role in the establishment and", "in the establishment and regulation", "the establishment and regulation of", "establishment and regulation of adherens", "and regulation of adherens junctions.", "regulation of adherens junctions. these", "of adherens junctions. these catenin", "adherens junctions. these catenin proteins", "junctions. these catenin proteins include", "these catenin proteins include ctnnd1", "proteins include ctnnd1 also", "include ctnnd1 also known", "ctnnd1 also known as", "also known as p120 catenin", "known as p120 catenin or", "as p120 catenin or delta", "p120 catenin or delta catenin", "delta catenin ctnnb1", "beta catenin jup", "junction plakoglobin also known", "plakoglobin also known as", "also known as gamma catenin", "gamma catenin and", "catenin and ctnna1", "and ctnna1 alpha catenin", "alpha catenin straub", "catenin straub et", "et al. 2003 kiener", "al. 2003 kiener et", "2003 kiener et al.", "et al. 2006 ortiz", "al. 2006 ortiz et", "2006 ortiz et al.", "et al. 2015 lee", "al. 2015 lee et", "2015 lee et al.", "lee et al. 2018 .

              cdh11", "al. 2018 .

              cdh11 through", "2018 .

              cdh11 through its", ".

              cdh11 through its c", "its c terminus also", "c terminus also forms", "terminus also forms a", "also forms a complex with", "forms a complex with angiomotin", "complex with angiomotin amot", "angiomotin amot isoform", "isoform p80 amot 2", "amot 2 which", "2 which is", "which is implicated in cdh11", "is implicated in cdh11 mediated", "implicated in cdh11 mediated cell", "in cdh11 mediated cell migration", "cdh11 mediated cell migration and", "mediated cell migration and tumor", "cell migration and tumor cell", "migration and tumor cell invasiveness", "tumor cell invasiveness levchenko", "cell invasiveness levchenko et", "invasiveness levchenko et al.", "et al. 2004 jiang", "al. 2004 jiang et", "2004 jiang et al.", "et al. 2006 yi", "al. 2006 yi et", "2006 yi et al.", "et al. 2011 ortiz", "al. 2011 ortiz et", "2011 ortiz et al.", "lee et al. 2018 .

              through", "et al. 2018 .

              through its", "al. 2018 .

              through its extracellular", "2018 .

              through its extracellular region", "its extracellular region cdh11", "extracellular region cdh11 binds", "region cdh11 binds to", "cdh11 binds to the c", "binds to the c terminal", "to the c terminal fragment", "the c terminal fragment of", "c terminal fragment of angptl4", "fragment of angptl4 angiopoietin", "of angptl4 angiopoietin like", "angptl4 angiopoietin like 4", "like 4 commonly", "4 commonly known", "known as cangptl4 which", "as cangptl4 which is", "cangptl4 which is implicated", "which is implicated in the", "is implicated in the regulation", "implicated in the regulation of", "in the regulation of wound", "the regulation of wound healing.", "regulation of wound healing. the", "of wound healing. the variant", "wound healing. the variant isoform", "healing. the variant isoform of", "the variant isoform of cdh11", "isoform of cdh11 cdh11v", "cdh11v an 85", "an 85 kda membrane bound", "kda membrane bound protein", "membrane bound protein produced", "bound protein produced as", "protein produced as a result", "produced as a result of", "as a result of alternative", "a result of alternative splicing", "of alternative splicing kawaguchi", "alternative splicing kawaguchi et", "splicing kawaguchi et al.", "al. 1999 can", "1999 can compete", "can compete with the canonical", "compete with the canonical cdh11", "with the canonical cdh11 for", "the canonical cdh11 for cangptl4", "canonical cdh11 for cangptl4 binding", "for cangptl4 binding teo", "cangptl4 binding teo et", "binding teo et al.", "teo et al. 2017 ." ] }, { "record_id": "GLY_000594_1_2114", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9762293", "r hsa", "hsa 9762293", "r hsa 9762293" ] }, { "record_id": "GLY_000594_1_2114", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of cdh11", "cdh11 gene", "gene transcription", "regulation of cdh11", "of cdh11 gene", "cdh11 gene transcription", "regulation of cdh11 gene", "of cdh11 gene transcription", "regulation of cdh11 gene transcription", "the cdh11", "gene consists", "consists of", "of 14", "14 exons", "which encode", "encode two", "two splice", "splice isoforms.", "isoforms. both", "both splicing", "splicing isoforms", "isoforms are", "are expressed", "expressed in", "in the", "the heart", "lung and", "and bone", "but not", "not in", "the kidney", "skeletal muscle", "pancreas and", "and liver", "okazaki et", "et al.", "al. 1994", "kawaguchi et", "al. 1999", "1999 .", ". several", "several transcription", "transcription factors", "factors have", "have been", "been shown", "shown to", "to directly", "directly regulate", "regulate cdh11", "including hoxc8", "lei et", "al. 2005", "al. 2006", "li et", "al. 2014", "zhang et", "al. 2017", "nam et", "al. 2012", "liu et", "al. 2020", "black et", "al. 2018", "and bhlhe22", "ross et", "and the", "the transcription", "transcription of", "cdh11 has", "has also", "also been", "to be", "be influenced", "influenced by", "by a", "a number", "number of", "of growth", "growth factors", "factors and", "and hormones", "such as", "as fgf2", "strutz et", "al. 2002", "james et", "al. 2008", "wu et", "al. 2013", "schneider et", "schulte et", "hahn et", "al. 2016", "cheng et", "ruan et", "al. 2019", "doolin et", "al. 2021", "wilson et", "al. 2022", "wecker et", "theodossiou et", "peng et", "al. 2015", "yao et", "lecanda et", "al. 2000", "chen et", ". cdh11", "cdh11 can", "can also", "also affect", "affect tgfb1", "tgfb1 signaling", "thereby possibly", "possibly creating", "creating a", "a feedback", "feedback loop", "passanha et", "2022 .", ". expression", "expression of", "of mouse", "mouse cdh11", "cdh11 in", "in mouse", "mouse osteoblast", "osteoblast like", "like cell", "cell line", "mc3t3 e1", "is not", "not affected", "affected by", "by osteogenic", "osteogenic hormones", "hormones triiodothyronine", "and 1", "1 25", "25 dihydroxyvitamin", "dihydroxyvitamin d3", "d3 at", "at either", "either mrna", "mrna or", "or protein", "protein levels", "leugmayr et", "2000 .", "the cdh11 gene", "cdh11 gene consists", "gene consists of", "consists of 14", "of 14 exons", "exons which", "which encode two", "encode two splice", "two splice isoforms.", "splice isoforms. both", "isoforms. both splicing", "both splicing isoforms", "splicing isoforms are", "isoforms are expressed", "are expressed in", "expressed in the", "in the heart", "heart brain", "brain placenta", "placenta lung", "lung and bone", "bone but", "but not in", "not in the", "in the kidney", "kidney skeletal", "muscle pancreas", "pancreas and liver", "liver okazaki", "okazaki et al.", "et al. 1994", "1994 kawaguchi", "kawaguchi et al.", "et al. 1999", "al. 1999 .", "1999 . several", ". several transcription", "several transcription factors", "transcription factors have", "factors have been", "have been shown", "been shown to", "shown to directly", "to directly regulate", "directly regulate cdh11", "regulate cdh11 gene", "transcription including", "hoxc8 lei", "lei et al.", "et al. 2005", "2005 lei", "et al. 2006", "2006 li", "li et al.", "et al. 2014", "ilf3 zhang", "zhang et al.", "et al. 2017", "zeb2 nam", "nam et al.", "et al. 2012", "2012 nam", "heyl liu", "liu et al.", "et al. 2020", "foxf1 black", "black et al.", "et al. 2018", "bhlhe22 ross", "ross et al.", "and the transcription", "the transcription of", "transcription of cdh11", "of cdh11 has", "cdh11 has also", "has also been", "also been shown", "shown to be", "to be influenced", "be influenced by", "influenced by a", "by a number", "a number of", "number of growth", "of growth factors", "growth factors and", "factors and hormones", "hormones such", "such as fgf2", "fgf2 strutz", "strutz et al.", "et al. 2002", "2002 james", "james et al.", "et al. 2008", "tnf wu", "wu et al.", "et al. 2013", "tgfb1 schneider", "schneider et al.", "2012 schulte", "schulte et al.", "2013 hahn", "hahn et al.", "et al. 2016", "2016 cheng", "cheng et al.", "2018 ruan", "ruan et al.", "et al. 2019", "2019 doolin", "doolin et al.", "et al. 2021", "2021 wilson", "wilson et al.", "et al. 2022", "tgfb2 wecker", "wecker et al.", "2013 theodossiou", "theodossiou et al.", "gnrh1 peng", "peng et al.", "et al. 2015", "pth yao", "yao et al.", "dexamethasone lecanda", "lecanda et al.", "et al. 2000", "progesterone chen", "chen et al.", "1999 . cdh11", ". cdh11 can", "cdh11 can also", "can also affect", "also affect tgfb1", "affect tgfb1 signaling", "signaling thereby", "thereby possibly creating", "possibly creating a", "creating a feedback", "a feedback loop", "loop passanha", "passanha et al.", "al. 2022 .", "2022 . expression", ". expression of", "expression of mouse", "of mouse cdh11", "mouse cdh11 in", "cdh11 in mouse", "in mouse osteoblast", "mouse osteoblast like", "osteoblast like cell", "like cell line", "line mc3t3", "e1 is", "is not affected", "not affected by", "affected by osteogenic", "by osteogenic hormones", "osteogenic hormones triiodothyronine", "triiodothyronine t3", "t3 and", "and 1 25", "1 25 dihydroxyvitamin", "25 dihydroxyvitamin d3", "dihydroxyvitamin d3 at", "d3 at either", "at either mrna", "either mrna or", "mrna or protein", "or protein levels", "levels leugmayr", "leugmayr et al.", "al. 2000 .", "the cdh11 gene consists", "cdh11 gene consists of", "gene consists of 14", "consists of 14 exons", "14 exons which", "exons which encode", "which encode two splice", "encode two splice isoforms.", "two splice isoforms. both", "splice isoforms. both splicing", "isoforms. both splicing isoforms", "both splicing isoforms are", "splicing isoforms are expressed", "isoforms are expressed in", "are expressed in the", "expressed in the heart", "the heart brain", "placenta lung and", "and bone but", "bone but not", "but not in the", "not in the kidney", "the kidney skeletal", "kidney skeletal muscle", "skeletal muscle pancreas", "muscle pancreas and", "and liver okazaki", "liver okazaki et", "okazaki et al. 1994", "al. 1994 kawaguchi", "1994 kawaguchi et", "kawaguchi et al. 1999", "et al. 1999 .", "al. 1999 . several", "1999 . several transcription", ". several transcription factors", "several transcription factors have", "transcription factors have been", "factors have been shown", "have been shown to", "been shown to directly", "shown to directly regulate", "to directly regulate cdh11", "directly regulate cdh11 gene", "regulate cdh11 gene transcription", "gene transcription including", "transcription including hoxc8", "including hoxc8 lei", "hoxc8 lei et", "lei et al. 2005", "al. 2005 lei", "2005 lei et", "lei et al. 2006", "al. 2006 li", "2006 li et", "li et al. 2014", "2014 ilf3", "ilf3 zhang et", "zhang et al. 2017", "2017 zeb2", "zeb2 nam et", "nam et al. 2012", "al. 2012 nam", "2012 nam et", "nam et al. 2014", "2014 heyl", "heyl liu et", "liu et al. 2020", "2020 foxf1", "foxf1 black et", "black et al. 2018", "2018 and", "and bhlhe22 ross", "bhlhe22 ross et", "ross et al. 2012", "2012 and", "and the transcription of", "the transcription of cdh11", "transcription of cdh11 has", "of cdh11 has also", "cdh11 has also been", "has also been shown", "also been shown to", "been shown to be", "shown to be influenced", "to be influenced by", "be influenced by a", "influenced by a number", "by a number of", "a number of growth", "number of growth factors", "of growth factors and", "growth factors and hormones", "and hormones such", "hormones such as", "as fgf2 strutz", "fgf2 strutz et", "strutz et al. 2002", "al. 2002 james", "2002 james et", "james et al. 2008", "2008 tnf", "tnf wu et", "wu et al. 2013", "2013 tgfb1", "tgfb1 schneider et", "schneider et al. 2012", "al. 2012 schulte", "2012 schulte et", "schulte et al. 2013", "al. 2013 hahn", "2013 hahn et", "hahn et al. 2016", "al. 2016 cheng", "2016 cheng et", "cheng et al. 2018", "al. 2018 ruan", "2018 ruan et", "ruan et al. 2019", "al. 2019 doolin", "2019 doolin et", "doolin et al. 2021", "al. 2021 wilson", "2021 wilson et", "wilson et al. 2022", "2022 tgfb2", "tgfb2 wecker et", "wecker et al. 2013", "al. 2013 theodossiou", "2013 theodossiou et", "theodossiou et al. 2019", "2019 gnrh1", "gnrh1 peng et", "peng et al. 2015", "2015 pth", "pth yao et", "yao et al. 2014", "2014 dexamethasone", "dexamethasone lecanda et", "lecanda et al. 2000", "2000 progesterone", "progesterone chen et", "chen et al. 1999", "al. 1999 . cdh11", "1999 . cdh11 can", ". cdh11 can also", "cdh11 can also affect", "can also affect tgfb1", "also affect tgfb1 signaling", "tgfb1 signaling thereby", "signaling thereby possibly", "thereby possibly creating a", "possibly creating a feedback", "creating a feedback loop", "feedback loop passanha", "loop passanha et", "passanha et al. 2022", "et al. 2022 .", "al. 2022 . expression", "2022 . expression of", ". expression of mouse", "expression of mouse cdh11", "of mouse cdh11 in", "mouse cdh11 in mouse", "cdh11 in mouse osteoblast", "in mouse osteoblast like", "mouse osteoblast like cell", "osteoblast like cell line", "cell line mc3t3", "line mc3t3 e1", "mc3t3 e1 is", "e1 is not", "is not affected by", "not affected by osteogenic", "affected by osteogenic hormones", "by osteogenic hormones triiodothyronine", "hormones triiodothyronine t3", "t3 and 1", "and 1 25 dihydroxyvitamin", "1 25 dihydroxyvitamin d3", "25 dihydroxyvitamin d3 at", "dihydroxyvitamin d3 at either", "d3 at either mrna", "at either mrna or", "either mrna or protein", "mrna or protein levels", "protein levels leugmayr", "levels leugmayr et", "leugmayr et al. 2000", "et al. 2000 .", "the cdh11 gene consists of", "cdh11 gene consists of 14", "gene consists of 14 exons", "of 14 exons which", "14 exons which encode", "exons which encode two", "which encode two splice isoforms.", "encode two splice isoforms. both", "two splice isoforms. both splicing", "splice isoforms. both splicing isoforms", "isoforms. both splicing isoforms are", "both splicing isoforms are expressed", "splicing isoforms are expressed in", "isoforms are expressed in the", "are expressed in the heart", "in the heart brain", "heart brain placenta", "brain placenta lung", "placenta lung and bone", "lung and bone but", "and bone but not", "bone but not in", "but not in the kidney", "in the kidney skeletal", "the kidney skeletal muscle", "skeletal muscle pancreas and", "muscle pancreas and liver", "pancreas and liver okazaki", "and liver okazaki et", "liver okazaki et al.", "et al. 1994 kawaguchi", "al. 1994 kawaguchi et", "1994 kawaguchi et al.", "kawaguchi et al. 1999 .", "et al. 1999 . several", "al. 1999 . several transcription", "1999 . several transcription factors", ". several transcription factors have", "several transcription factors have been", "transcription factors have been shown", "factors have been shown to", "have been shown to directly", "been shown to directly regulate", "shown to directly regulate cdh11", "to directly regulate cdh11 gene", "directly regulate cdh11 gene transcription", "cdh11 gene transcription including", "gene transcription including hoxc8", "including hoxc8 lei et", "hoxc8 lei et al.", "et al. 2005 lei", "al. 2005 lei et", "2005 lei et al.", "et al. 2006 li", "al. 2006 li et", "2006 li et al.", "al. 2014 ilf3", "ilf3 zhang et al.", "al. 2017 zeb2", "zeb2 nam et al.", "et al. 2012 nam", "al. 2012 nam et", "2012 nam et al.", "al. 2014 heyl", "heyl liu et al.", "al. 2020 foxf1", "foxf1 black et al.", "al. 2018 and", "2018 and bhlhe22", "and bhlhe22 ross et", "bhlhe22 ross et al.", "al. 2012 and", "2012 and the", "and the transcription of cdh11", "the transcription of cdh11 has", "transcription of cdh11 has also", "of cdh11 has also been", "cdh11 has also been shown", "has also been shown to", "also been shown to be", "been shown to be influenced", "shown to be influenced by", "to be influenced by a", "be influenced by a number", "influenced by a number of", "by a number of growth", "a number of growth factors", "number of growth factors and", "of growth factors and hormones", "factors and hormones such", "and hormones such as", "hormones such as fgf2", "such as fgf2 strutz", "as fgf2 strutz et", "fgf2 strutz et al.", "et al. 2002 james", "al. 2002 james et", "2002 james et al.", "al. 2008 tnf", "tnf wu et al.", "al. 2013 tgfb1", "tgfb1 schneider et al.", "et al. 2012 schulte", "al. 2012 schulte et", "2012 schulte et al.", "et al. 2013 hahn", "al. 2013 hahn et", "2013 hahn et al.", "et al. 2016 cheng", "al. 2016 cheng et", "2016 cheng et al.", "et al. 2018 ruan", "al. 2018 ruan et", "2018 ruan et al.", "et al. 2019 doolin", "al. 2019 doolin et", "2019 doolin et al.", "et al. 2021 wilson", "al. 2021 wilson et", "2021 wilson et al.", "al. 2022 tgfb2", "tgfb2 wecker et al.", "et al. 2013 theodossiou", "al. 2013 theodossiou et", "2013 theodossiou et al.", "al. 2019 gnrh1", "gnrh1 peng et al.", "al. 2015 pth", "pth yao et al.", "al. 2014 dexamethasone", "dexamethasone lecanda et al.", "al. 2000 progesterone", "progesterone chen et al.", "chen et al. 1999 .", "et al. 1999 . cdh11", "al. 1999 . cdh11 can", "1999 . cdh11 can also", ". cdh11 can also affect", "cdh11 can also affect tgfb1", "can also affect tgfb1 signaling", "affect tgfb1 signaling thereby", "tgfb1 signaling thereby possibly", "signaling thereby possibly creating", "thereby possibly creating a feedback", "possibly creating a feedback loop", "a feedback loop passanha", "feedback loop passanha et", "loop passanha et al.", "passanha et al. 2022 .", "et al. 2022 . expression", "al. 2022 . expression of", "2022 . expression of mouse", ". expression of mouse cdh11", "expression of mouse cdh11 in", "of mouse cdh11 in mouse", "mouse cdh11 in mouse osteoblast", "cdh11 in mouse osteoblast like", "in mouse osteoblast like cell", "mouse osteoblast like cell line", "like cell line mc3t3", "cell line mc3t3 e1", "mc3t3 e1 is not", "e1 is not affected", "is not affected by osteogenic", "not affected by osteogenic hormones", "affected by osteogenic hormones triiodothyronine", "osteogenic hormones triiodothyronine t3", "triiodothyronine t3 and", "t3 and 1 25", "and 1 25 dihydroxyvitamin d3", "1 25 dihydroxyvitamin d3 at", "25 dihydroxyvitamin d3 at either", "dihydroxyvitamin d3 at either mrna", "d3 at either mrna or", "at either mrna or protein", "either mrna or protein levels", "or protein levels leugmayr", "protein levels leugmayr et", "levels leugmayr et al.", "leugmayr et al. 2000 ." ] }, { "record_id": "GLY_000594_1_2115", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9764302", "r hsa", "hsa 9764302", "r hsa 9764302" ] }, { "record_id": "GLY_000594_1_2115", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of cdh19", "cdh19 expression", "expression and", "and function", "regulation of cdh19", "of cdh19 expression", "cdh19 expression and", "expression and function", "regulation of cdh19 expression", "of cdh19 expression and", "cdh19 expression and function", "regulation of cdh19 expression and", "of cdh19 expression and function", "cadherin 19", "also known", "known as", "as cdh7l2", "is a", "a classical", "classical type", "type ii", "ii cadherin.", "cadherin. the", "the human", "human cdh19", "cdh19 gene", "gene is", "a part", "part of", "of the", "the cadherin", "cadherin gene", "gene cluster", "cluster at", "at the", "the chromosomal", "chromosomal bands", "bands 18q22", "18q22 q23", "together with", "with cdh7", "cdh7 and", "and cdh20", "kools et", "et al.", "al. 2000", "2000 .", ". at", "the plasma", "plasma membrane", "cdh19 associates", "associates with", "with alpha", "alpha catenin", "beta catenin", "gamma catenin", "and delta", "delta catenin", "huang et", "al. 2022", "like other", "other classical", "type i", "i and", "and type", "ii cadherins.", "cadherins. cdh19", "cdh19 possesses", "possesses five", "five extracellular", "extracellular cadherin", "cadherin domains", "domains and", "classical cadherins", "is thought", "thought to", "to play", "play a", "a role", "role in", "in the", "the establishment", "establishment of", "of homotypic", "homotypic cell", "cell cell", "cell adhesions", "adhesions during", "during formation", "formation of", "of adherens", "adherens junctions.

              in", "junctions.

              in rat", "the expression", "expression of", "cdh19 overlaps", "overlaps with", "with the", "the neural", "neural crest", "crest cell", "cell marker", "marker sox10", "takahashi and", "and osumi", "osumi 2005", "2005 .", ". in", "in mouse", "it was", "was shown", "shown that", "that sox10", "sox10 transcription", "transcription factor", "essential for", "for migration", "migration of", "of neural", "crest cells", "cells during", "the enteric", "enteric nervous", "nervous system", "binds to", "to the", "the cdh19", "gene promoter", "promoter and", "and stimulates", "stimulates cdh19", "cdh19 transcription.", "transcription. cdh19", "cdh19 knockdown", "knockdown results", "results in", "in retarded", "retarded sacral", "sacral migration", "while re", "re expression", "cdh19 partially", "partially rescues", "rescues retarded", "retarded migration", "of sox10", "sox10 null", "null neural", "2022 .", ". cdh19", "cdh19 is", "a specific", "specific marker", "marker of", "of schwann", "schwann cell", "cell precursors", "iribar et", "al. 2016", "stratton et", "al. 2017", "george et", "al. 2018", "woods et", "al. 2021", "2021 .

              during", ".

              during angiogenesis", "in response", "response to", "to monocyte", "monocyte chemotactic", "chemotactic protein", "protein 1", "mcp 1", "as ccl2", "ccl2 or", "or c", "c c", "c motif", "motif chemokine", "chemokine 2", "cdh19 transcription", "transcription is", "is directly", "directly stimulated", "stimulated by", "by zc3h12a", "for mcp", "1 induced", "induced protein", "niu et", "al. 2008", "al. 2013", "2013 .", "cdh19 was", "was found", "found to", "to be", "be a", "a target", "target of", "of microrna", "microrna mir", "mir 197", "197 5p.", "5p. the", "the circular", "circular rna", "rna hsa_circ_006220", "hsa_circ_006220 was", "shown to", "to sponge", "sponge mir", "197 5p", "5p and", "and lead", "lead to", "to upregulation", "upregulation of", "cdh19 mrna", "mrna and", "and protein", "protein levels", "shi et", "2021 .", ". circular", "circular rnas", "rnas that", "that possess", "possess multiple", "multiple microrna", "microrna binding", "binding sites", "sites act", "act as", "as sponges", "sponges that", "by binding", "binding to", "to micrornas", "prevent these", "these micrornas", "micrornas from", "from associating", "associating with", "with their", "their target", "target mrnas.

              both", "mrnas.

              both upregulation", "upregulation and", "and downregulation", "downregulation of", "cdh19 have", "have been", "been reported", "reported in", "in cancer", "cancer and", "and it", "it has", "has been", "been proposed", "proposed to", "play both", "both oncogenic", "oncogenic and", "and tumor", "tumor suppressive", "suppressive roles", "depending on", "on the", "the cancer", "cancer type.", "type. cdh19", "mrna is", "is upregulated", "upregulated in", "in clear", "clear cell", "cell sarcoma", "sarcoma and", "and correlates", "correlates with", "with a", "a hypomethylated", "hypomethylated profile", "dermawan et", "in glioblastoma", "cancer stem", "stem like", "like cells", "zorniak et", "al. 2015", "2015 .", "in colorectal", "colorectal tumors", "upregulated compared", "compared to", "to normal", "normal tissue", "bujko et", ". downregulation", "is an", "an independent", "independent prognostic", "prognostic biomarker", "biomarker of", "the outcome", "outcome of", "of lung", "lung adenocarcinoma", "li et", "in triple", "triple negative", "negative breast", "breast cancer", "was proposed", "a tumor", "tumor suppressor", "suppressor role", ". a", "a homozygous", "homozygous deletion", "deletion of", "gene was", "was reported", "in a", "a portion", "portion of", "of chondrosarcoma", "chondrosarcoma tumor", "tumor samples", "niini et", "al. 2012", "2012 .", "19 cdh19", "cdh19 also", "also known as", "known as cdh7l2", "cdh7l2 is", "is a classical", "a classical type", "classical type ii", "type ii cadherin.", "ii cadherin. the", "cadherin. the human", "the human cdh19", "human cdh19 gene", "cdh19 gene is", "gene is a", "is a part", "a part of", "part of the", "of the cadherin", "the cadherin gene", "cadherin gene cluster", "gene cluster at", "cluster at the", "at the chromosomal", "the chromosomal bands", "chromosomal bands 18q22", "bands 18q22 q23", "q23 together", "together with cdh7", "with cdh7 and", "cdh7 and cdh20", "cdh20 kools", "kools et al.", "et al. 2000", "al. 2000 .", "2000 . at", ". at the", "at the plasma", "the plasma membrane", "membrane cdh19", "cdh19 associates with", "associates with alpha", "with alpha catenin", "catenin ctnna1", "catenin ctnnb1", "catenin jup", "jup and", "and delta catenin", "catenin ctnnd1", "huang et al.", "et al. 2022", "like other classical", "other classical type", "classical type i", "type i and", "i and type", "and type ii", "type ii cadherins.", "ii cadherins. cdh19", "cadherins. cdh19 possesses", "cdh19 possesses five", "possesses five extracellular", "five extracellular cadherin", "extracellular cadherin domains", "cadherin domains and", "and like", "other classical cadherins", "cadherins is", "is thought to", "thought to play", "to play a", "play a role", "a role in", "role in the", "in the establishment", "the establishment of", "establishment of homotypic", "of homotypic cell", "homotypic cell cell", "cell cell adhesions", "cell adhesions during", "adhesions during formation", "during formation of", "formation of adherens", "of adherens junctions.

              in", "adherens junctions.

              in rat", "rat the", "the expression of", "expression of cdh19", "of cdh19 overlaps", "cdh19 overlaps with", "overlaps with the", "with the expression", "expression of the", "of the neural", "the neural crest", "neural crest cell", "crest cell marker", "cell marker sox10", "sox10 takahashi", "takahashi and osumi", "and osumi 2005", "osumi 2005 .", "2005 . in", ". in mouse", "mouse it", "it was shown", "was shown that", "shown that sox10", "that sox10 transcription", "sox10 transcription factor", "factor essential", "essential for migration", "for migration of", "migration of neural", "of neural crest", "neural crest cells", "crest cells during", "cells during formation", "formation of the", "of the enteric", "the enteric nervous", "enteric nervous system", "system binds", "binds to the", "to the cdh19", "the cdh19 gene", "cdh19 gene promoter", "gene promoter and", "promoter and stimulates", "and stimulates cdh19", "stimulates cdh19 transcription.", "cdh19 transcription. cdh19", "transcription. cdh19 knockdown", "cdh19 knockdown results", "knockdown results in", "results in retarded", "in retarded sacral", "retarded sacral migration", "sacral migration of", "cells while", "while re expression", "re expression of", "of cdh19 partially", "cdh19 partially rescues", "partially rescues retarded", "rescues retarded migration", "retarded migration of", "migration of sox10", "of sox10 null", "sox10 null neural", "null neural crest", "cells huang", "al. 2022 .", "2022 . cdh19", ". cdh19 is", "cdh19 is a", "is a specific", "a specific marker", "specific marker of", "marker of schwann", "of schwann cell", "schwann cell precursors", "precursors takahashi", "2005 iribar", "iribar et al.", "et al. 2016", "2016 stratton", "stratton et al.", "et al. 2017", "2017 george", "george et al.", "et al. 2018", "2018 woods", "woods et al.", "et al. 2021", "al. 2021 .

              during", "2021 .

              during angiogenesis", "angiogenesis in", "in response to", "response to monocyte", "to monocyte chemotactic", "monocyte chemotactic protein", "chemotactic protein 1", "1 mcp", "1 also", "known as ccl2", "as ccl2 or", "ccl2 or c", "or c c", "c c motif", "c motif chemokine", "motif chemokine 2", "cdh19 transcription is", "transcription is directly", "is directly stimulated", "directly stimulated by", "stimulated by zc3h12a", "zc3h12a mcpip", "mcpip for", "for mcp 1", "mcp 1 induced", "1 induced protein", "niu et al.", "et al. 2008", "2008 niu", "et al. 2013", "al. 2013 .", "2013 . cdh19", ". cdh19 was", "cdh19 was found", "was found to", "found to be", "to be a", "be a target", "a target of", "target of microrna", "of microrna mir", "microrna mir 197", "mir 197 5p.", "197 5p. the", "5p. the circular", "the circular rna", "circular rna hsa_circ_006220", "rna hsa_circ_006220 was", "hsa_circ_006220 was shown", "was shown to", "shown to sponge", "to sponge mir", "sponge mir 197", "mir 197 5p", "197 5p and", "5p and lead", "and lead to", "lead to upregulation", "to upregulation of", "upregulation of cdh19", "of cdh19 mrna", "cdh19 mrna and", "mrna and protein", "and protein levels", "levels shi", "shi et al.", "al. 2021 .", "2021 . circular", ". circular rnas", "circular rnas that", "rnas that possess", "that possess multiple", "possess multiple microrna", "multiple microrna binding", "microrna binding sites", "binding sites act", "sites act as", "act as sponges", "as sponges that", "that by", "by binding to", "binding to micrornas", "micrornas prevent", "prevent these micrornas", "these micrornas from", "micrornas from associating", "from associating with", "associating with their", "with their target", "their target mrnas.

              both", "target mrnas.

              both upregulation", "mrnas.

              both upregulation and", "upregulation and downregulation", "and downregulation of", "downregulation of cdh19", "of cdh19 have", "cdh19 have been", "have been reported", "been reported in", "reported in cancer", "in cancer and", "cancer and it", "and it has", "it has been", "has been proposed", "been proposed to", "proposed to play", "to play both", "play both oncogenic", "both oncogenic and", "oncogenic and tumor", "and tumor suppressive", "tumor suppressive roles", "roles depending", "depending on the", "on the cancer", "the cancer type.", "cancer type. cdh19", "type. cdh19 mrna", "cdh19 mrna is", "mrna is upregulated", "is upregulated in", "upregulated in clear", "in clear cell", "clear cell sarcoma", "cell sarcoma and", "sarcoma and correlates", "and correlates with", "correlates with a", "with a hypomethylated", "a hypomethylated profile", "profile dermawan", "dermawan et al.", "2022 . in", ". in glioblastoma", "glioblastoma cdh19", "cdh19 is upregulated", "upregulated in cancer", "in cancer stem", "cancer stem like", "stem like cells", "cells zorniak", "zorniak et al.", "et al. 2015", "al. 2015 .", "2015 . in", ". in colorectal", "in colorectal tumors", "tumors cdh19", "is upregulated compared", "upregulated compared to", "compared to normal", "to normal tissue", "tissue bujko", "bujko et al.", "2015 . downregulation", ". downregulation of", "of cdh19 is", "cdh19 is an", "is an independent", "an independent prognostic", "independent prognostic biomarker", "prognostic biomarker of", "biomarker of the", "of the outcome", "the outcome of", "outcome of lung", "of lung adenocarcinoma", "adenocarcinoma li", "li et al.", ". in triple", "in triple negative", "triple negative breast", "negative breast cancer", "cancer cdh19", "cdh19 was proposed", "was proposed to", "play a tumor", "a tumor suppressor", "tumor suppressor role", "role shi", "2021 . a", ". a homozygous", "a homozygous deletion", "homozygous deletion of", "deletion of the", "of the cdh19", "cdh19 gene was", "gene was reported", "was reported in", "reported in a", "in a portion", "a portion of", "portion of chondrosarcoma", "of chondrosarcoma tumor", "chondrosarcoma tumor samples", "samples niini", "niini et al.", "et al. 2012", "al. 2012 .", "cadherin 19 cdh19", "cdh19 also known", "also known as cdh7l2", "as cdh7l2 is", "cdh7l2 is a", "is a classical type", "a classical type ii", "classical type ii cadherin.", "type ii cadherin. the", "ii cadherin. the human", "cadherin. the human cdh19", "the human cdh19 gene", "human cdh19 gene is", "cdh19 gene is a", "gene is a part", "is a part of", "a part of the", "part of the cadherin", "of the cadherin gene", "the cadherin gene cluster", "cadherin gene cluster at", "gene cluster at the", "cluster at the chromosomal", "at the chromosomal bands", "the chromosomal bands 18q22", "chromosomal bands 18q22 q23", "18q22 q23 together", "q23 together with", "together with cdh7 and", "with cdh7 and cdh20", "and cdh20 kools", "cdh20 kools et", "kools et al. 2000", "et al. 2000 .", "al. 2000 . at", "2000 . at the", ". at the plasma", "at the plasma membrane", "plasma membrane cdh19", "membrane cdh19 associates", "cdh19 associates with alpha", "associates with alpha catenin", "alpha catenin ctnna1", "ctnna1 beta", "beta catenin ctnnb1", "ctnnb1 gamma", "gamma catenin jup", "jup and delta", "delta catenin ctnnd1", "ctnnd1 huang", "huang et al. 2022", "2022 like", "like other classical type", "other classical type i", "classical type i and", "type i and type", "i and type ii", "and type ii cadherins.", "type ii cadherins. cdh19", "ii cadherins. cdh19 possesses", "cadherins. cdh19 possesses five", "cdh19 possesses five extracellular", "possesses five extracellular cadherin", "five extracellular cadherin domains", "extracellular cadherin domains and", "domains and like", "and like other", "like other classical cadherins", "classical cadherins is", "cadherins is thought", "is thought to play", "thought to play a", "to play a role", "play a role in", "a role in the", "role in the establishment", "in the establishment of", "the establishment of homotypic", "establishment of homotypic cell", "of homotypic cell cell", "homotypic cell cell adhesions", "cell cell adhesions during", "cell adhesions during formation", "adhesions during formation of", "during formation of adherens", "formation of adherens junctions.

              in", "of adherens junctions.

              in rat", "junctions.

              in rat the", "rat the expression", "the expression of cdh19", "expression of cdh19 overlaps", "of cdh19 overlaps with", "cdh19 overlaps with the", "overlaps with the expression", "with the expression of", "the expression of the", "expression of the neural", "of the neural crest", "the neural crest cell", "neural crest cell marker", "crest cell marker sox10", "marker sox10 takahashi", "sox10 takahashi and", "takahashi and osumi 2005", "and osumi 2005 .", "osumi 2005 . in", "2005 . in mouse", "in mouse it", "mouse it was", "it was shown that", "was shown that sox10", "shown that sox10 transcription", "that sox10 transcription factor", "transcription factor essential", "factor essential for", "essential for migration of", "for migration of neural", "migration of neural crest", "of neural crest cells", "neural crest cells during", "crest cells during formation", "cells during formation of", "during formation of the", "formation of the enteric", "of the enteric nervous", "the enteric nervous system", "nervous system binds", "system binds to", "binds to the cdh19", "to the cdh19 gene", "the cdh19 gene promoter", "cdh19 gene promoter and", "gene promoter and stimulates", "promoter and stimulates cdh19", "and stimulates cdh19 transcription.", "stimulates cdh19 transcription. cdh19", "cdh19 transcription. cdh19 knockdown", "transcription. cdh19 knockdown results", "cdh19 knockdown results in", "knockdown results in retarded", "results in retarded sacral", "in retarded sacral migration", "retarded sacral migration of", "sacral migration of neural", "crest cells while", "cells while re", "while re expression of", "re expression of cdh19", "expression of cdh19 partially", "of cdh19 partially rescues", "cdh19 partially rescues retarded", "partially rescues retarded migration", "rescues retarded migration of", "retarded migration of sox10", "migration of sox10 null", "of sox10 null neural", "sox10 null neural crest", "null neural crest cells", "crest cells huang", "cells huang et", "et al. 2022 .", "al. 2022 . cdh19", "2022 . cdh19 is", ". cdh19 is a", "cdh19 is a specific", "is a specific marker", "a specific marker of", "specific marker of schwann", "marker of schwann cell", "of schwann cell precursors", "cell precursors takahashi", "precursors takahashi and", "osumi 2005 iribar", "2005 iribar et", "iribar et al. 2016", "al. 2016 stratton", "2016 stratton et", "stratton et al. 2017", "al. 2017 george", "2017 george et", "george et al. 2018", "al. 2018 woods", "2018 woods et", "woods et al. 2021", "et al. 2021 .

              during", "al. 2021 .

              during angiogenesis", ".

              during angiogenesis in", "angiogenesis in response", "in response to monocyte", "response to monocyte chemotactic", "to monocyte chemotactic protein", "monocyte chemotactic protein 1", "protein 1 mcp", "1 mcp 1", "mcp 1 also", "1 also known", "also known as ccl2", "known as ccl2 or", "as ccl2 or c", "ccl2 or c c", "or c c motif", "c c motif chemokine", "c motif chemokine 2", "2 cdh19", "cdh19 transcription is directly", "transcription is directly stimulated", "is directly stimulated by", "directly stimulated by zc3h12a", "by zc3h12a mcpip", "mcpip for mcp", "for mcp 1 induced", "mcp 1 induced protein", "protein niu", "niu et al. 2008", "al. 2008 niu", "2008 niu et", "niu et al. 2013", "et al. 2013 .", "al. 2013 . cdh19", "2013 . cdh19 was", ". cdh19 was found", "cdh19 was found to", "was found to be", "found to be a", "to be a target", "be a target of", "a target of microrna", "target of microrna mir", "of microrna mir 197", "microrna mir 197 5p.", "mir 197 5p. the", "197 5p. the circular", "5p. the circular rna", "the circular rna hsa_circ_006220", "circular rna hsa_circ_006220 was", "rna hsa_circ_006220 was shown", "hsa_circ_006220 was shown to", "was shown to sponge", "shown to sponge mir", "to sponge mir 197", "sponge mir 197 5p", "mir 197 5p and", "197 5p and lead", "5p and lead to", "and lead to upregulation", "lead to upregulation of", "to upregulation of cdh19", "upregulation of cdh19 mrna", "of cdh19 mrna and", "cdh19 mrna and protein", "mrna and protein levels", "protein levels shi", "levels shi et", "shi et al. 2021", "et al. 2021 .", "al. 2021 . circular", "2021 . circular rnas", ". circular rnas that", "circular rnas that possess", "rnas that possess multiple", "that possess multiple microrna", "possess multiple microrna binding", "multiple microrna binding sites", "microrna binding sites act", "binding sites act as", "sites act as sponges", "act as sponges that", "sponges that by", "that by binding", "by binding to micrornas", "to micrornas prevent", "micrornas prevent these", "prevent these micrornas from", "these micrornas from associating", "micrornas from associating with", "from associating with their", "associating with their target", "with their target mrnas.

              both", "their target mrnas.

              both upregulation", "target mrnas.

              both upregulation and", "mrnas.

              both upregulation and downregulation", "upregulation and downregulation of", "and downregulation of cdh19", "downregulation of cdh19 have", "of cdh19 have been", "cdh19 have been reported", "have been reported in", "been reported in cancer", "reported in cancer and", "in cancer and it", "cancer and it has", "and it has been", "it has been proposed", "has been proposed to", "been proposed to play", "proposed to play both", "to play both oncogenic", "play both oncogenic and", "both oncogenic and tumor", "oncogenic and tumor suppressive", "and tumor suppressive roles", "suppressive roles depending", "roles depending on", "depending on the cancer", "on the cancer type.", "the cancer type. cdh19", "cancer type. cdh19 mrna", "type. cdh19 mrna is", "cdh19 mrna is upregulated", "mrna is upregulated in", "is upregulated in clear", "upregulated in clear cell", "in clear cell sarcoma", "clear cell sarcoma and", "cell sarcoma and correlates", "sarcoma and correlates with", "and correlates with a", "correlates with a hypomethylated", "with a hypomethylated profile", "hypomethylated profile dermawan", "profile dermawan et", "dermawan et al. 2022", "al. 2022 . in", "2022 . in glioblastoma", "in glioblastoma cdh19", "glioblastoma cdh19 is", "cdh19 is upregulated in", "is upregulated in cancer", "upregulated in cancer stem", "in cancer stem like", "cancer stem like cells", "like cells zorniak", "cells zorniak et", "zorniak et al. 2015", "et al. 2015 .", "al. 2015 . in", "2015 . in colorectal", ". in colorectal tumors", "colorectal tumors cdh19", "tumors cdh19 is", "cdh19 is upregulated compared", "is upregulated compared to", "upregulated compared to normal", "compared to normal tissue", "normal tissue bujko", "tissue bujko et", "bujko et al. 2015", "al. 2015 . downregulation", "2015 . downregulation of", ". downregulation of cdh19", "downregulation of cdh19 is", "of cdh19 is an", "cdh19 is an independent", "is an independent prognostic", "an independent prognostic biomarker", "independent prognostic biomarker of", "prognostic biomarker of the", "biomarker of the outcome", "of the outcome of", "the outcome of lung", "outcome of lung adenocarcinoma", "lung adenocarcinoma li", "adenocarcinoma li et", "li et al. 2022", "2022 . in triple", ". in triple negative", "in triple negative breast", "triple negative breast cancer", "breast cancer cdh19", "cancer cdh19 was", "cdh19 was proposed to", "was proposed to play", "proposed to play a", "to play a tumor", "play a tumor suppressor", "a tumor suppressor role", "suppressor role shi", "role shi et", "al. 2021 . a", "2021 . a homozygous", ". a homozygous deletion", "a homozygous deletion of", "homozygous deletion of the", "deletion of the cdh19", "of the cdh19 gene", "the cdh19 gene was", "cdh19 gene was reported", "gene was reported in", "was reported in a", "reported in a portion", "in a portion of", "a portion of chondrosarcoma", "portion of chondrosarcoma tumor", "of chondrosarcoma tumor samples", "tumor samples niini", "samples niini et", "niini et al. 2012", "et al. 2012 .", "19 cdh19 also", "cdh19 also known as", "known as cdh7l2 is", "as cdh7l2 is a", "cdh7l2 is a classical", "is a classical type ii", "a classical type ii cadherin.", "classical type ii cadherin. the", "type ii cadherin. the human", "ii cadherin. the human cdh19", "cadherin. the human cdh19 gene", "the human cdh19 gene is", "human cdh19 gene is a", "cdh19 gene is a part", "gene is a part of", "is a part of the", "a part of the cadherin", "part of the cadherin gene", "of the cadherin gene cluster", "the cadherin gene cluster at", "cadherin gene cluster at the", "gene cluster at the chromosomal", "cluster at the chromosomal bands", "at the chromosomal bands 18q22", "the chromosomal bands 18q22 q23", "bands 18q22 q23 together", "18q22 q23 together with", "q23 together with cdh7", "together with cdh7 and cdh20", "cdh7 and cdh20 kools", "and cdh20 kools et", "cdh20 kools et al.", "kools et al. 2000 .", "et al. 2000 . at", "al. 2000 . at the", "2000 . at the plasma", ". at the plasma membrane", "the plasma membrane cdh19", "plasma membrane cdh19 associates", "membrane cdh19 associates with", "cdh19 associates with alpha catenin", "with alpha catenin ctnna1", "ctnna1 beta catenin", "ctnnb1 gamma catenin", "catenin jup and", "jup and delta catenin", "and delta catenin ctnnd1", "ctnnd1 huang et", "al. 2022 like", "2022 like other", "like other classical type i", "other classical type i and", "classical type i and type", "type i and type ii", "i and type ii cadherins.", "and type ii cadherins. cdh19", "type ii cadherins. cdh19 possesses", "ii cadherins. cdh19 possesses five", "cadherins. cdh19 possesses five extracellular", "cdh19 possesses five extracellular cadherin", "possesses five extracellular cadherin domains", "five extracellular cadherin domains and", "cadherin domains and like", "domains and like other", "and like other classical", "other classical cadherins is", "classical cadherins is thought", "cadherins is thought to", "is thought to play a", "thought to play a role", "to play a role in", "play a role in the", "a role in the establishment", "role in the establishment of", "in the establishment of homotypic", "the establishment of homotypic cell", "establishment of homotypic cell cell", "of homotypic cell cell adhesions", "homotypic cell cell adhesions during", "cell cell adhesions during formation", "cell adhesions during formation of", "adhesions during formation of adherens", "during formation of adherens junctions.

              in", "formation of adherens junctions.

              in rat", "adherens junctions.

              in rat the", "junctions.

              in rat the expression", "rat the expression of", "the expression of cdh19 overlaps", "expression of cdh19 overlaps with", "of cdh19 overlaps with the", "cdh19 overlaps with the expression", "overlaps with the expression of", "with the expression of the", "the expression of the neural", "expression of the neural crest", "of the neural crest cell", "the neural crest cell marker", "neural crest cell marker sox10", "cell marker sox10 takahashi", "marker sox10 takahashi and", "sox10 takahashi and osumi", "takahashi and osumi 2005 .", "and osumi 2005 . in", "osumi 2005 . in mouse", ". in mouse it", "in mouse it was", "mouse it was shown", "it was shown that sox10", "was shown that sox10 transcription", "shown that sox10 transcription factor", "sox10 transcription factor essential", "transcription factor essential for", "factor essential for migration", "essential for migration of neural", "for migration of neural crest", "migration of neural crest cells", "of neural crest cells during", "neural crest cells during formation", "crest cells during formation of", "cells during formation of the", "during formation of the enteric", "formation of the enteric nervous", "of the enteric nervous system", "enteric nervous system binds", "nervous system binds to", "system binds to the", "binds to the cdh19 gene", "to the cdh19 gene promoter", "the cdh19 gene promoter and", "cdh19 gene promoter and stimulates", "gene promoter and stimulates cdh19", "promoter and stimulates cdh19 transcription.", "and stimulates cdh19 transcription. cdh19", "stimulates cdh19 transcription. cdh19 knockdown", "cdh19 transcription. cdh19 knockdown results", "transcription. cdh19 knockdown results in", "cdh19 knockdown results in retarded", "knockdown results in retarded sacral", "results in retarded sacral migration", "in retarded sacral migration of", "retarded sacral migration of neural", "sacral migration of neural crest", "neural crest cells while", "crest cells while re", "cells while re expression", "while re expression of cdh19", "re expression of cdh19 partially", "expression of cdh19 partially rescues", "of cdh19 partially rescues retarded", "cdh19 partially rescues retarded migration", "partially rescues retarded migration of", "rescues retarded migration of sox10", "retarded migration of sox10 null", "migration of sox10 null neural", "of sox10 null neural crest", "sox10 null neural crest cells", "neural crest cells huang", "crest cells huang et", "cells huang et al.", "huang et al. 2022 .", "et al. 2022 . cdh19", "al. 2022 . cdh19 is", "2022 . cdh19 is a", ". cdh19 is a specific", "cdh19 is a specific marker", "is a specific marker of", "a specific marker of schwann", "specific marker of schwann cell", "marker of schwann cell precursors", "schwann cell precursors takahashi", "cell precursors takahashi and", "precursors takahashi and osumi", "and osumi 2005 iribar", "osumi 2005 iribar et", "2005 iribar et al.", "et al. 2016 stratton", "al. 2016 stratton et", "2016 stratton et al.", "et al. 2017 george", "al. 2017 george et", "2017 george et al.", "et al. 2018 woods", "al. 2018 woods et", "2018 woods et al.", "woods et al. 2021 .

              during", "et al. 2021 .

              during angiogenesis", "2021 .

              during angiogenesis in", ".

              during angiogenesis in response", "angiogenesis in response to", "in response to monocyte chemotactic", "response to monocyte chemotactic protein", "to monocyte chemotactic protein 1", "chemotactic protein 1 mcp", "protein 1 mcp 1", "mcp 1 also known", "1 also known as", "also known as ccl2 or", "known as ccl2 or c", "as ccl2 or c c", "ccl2 or c c motif", "or c c motif chemokine", "c c motif chemokine 2", "chemokine 2 cdh19", "2 cdh19 transcription", "cdh19 transcription is directly stimulated", "transcription is directly stimulated by", "is directly stimulated by zc3h12a", "stimulated by zc3h12a mcpip", "zc3h12a mcpip for", "mcpip for mcp 1", "for mcp 1 induced protein", "induced protein niu", "protein niu et", "et al. 2008 niu", "al. 2008 niu et", "2008 niu et al.", "niu et al. 2013 .", "et al. 2013 . cdh19", "al. 2013 . cdh19 was", "2013 . cdh19 was found", ". cdh19 was found to", "cdh19 was found to be", "was found to be a", "found to be a target", "to be a target of", "be a target of microrna", "a target of microrna mir", "target of microrna mir 197", "of microrna mir 197 5p.", "microrna mir 197 5p. the", "mir 197 5p. the circular", "197 5p. the circular rna", "5p. the circular rna hsa_circ_006220", "the circular rna hsa_circ_006220 was", "circular rna hsa_circ_006220 was shown", "rna hsa_circ_006220 was shown to", "hsa_circ_006220 was shown to sponge", "was shown to sponge mir", "shown to sponge mir 197", "to sponge mir 197 5p", "sponge mir 197 5p and", "mir 197 5p and lead", "197 5p and lead to", "5p and lead to upregulation", "and lead to upregulation of", "lead to upregulation of cdh19", "to upregulation of cdh19 mrna", "upregulation of cdh19 mrna and", "of cdh19 mrna and protein", "cdh19 mrna and protein levels", "and protein levels shi", "protein levels shi et", "levels shi et al.", "shi et al. 2021 .", "et al. 2021 . circular", "al. 2021 . circular rnas", "2021 . circular rnas that", ". circular rnas that possess", "circular rnas that possess multiple", "rnas that possess multiple microrna", "that possess multiple microrna binding", "possess multiple microrna binding sites", "multiple microrna binding sites act", "microrna binding sites act as", "binding sites act as sponges", "sites act as sponges that", "as sponges that by", "sponges that by binding", "that by binding to", "binding to micrornas prevent", "to micrornas prevent these", "micrornas prevent these micrornas", "prevent these micrornas from associating", "these micrornas from associating with", "micrornas from associating with their", "from associating with their target", "associating with their target mrnas.

              both", "with their target mrnas.

              both upregulation", "their target mrnas.

              both upregulation and", "target mrnas.

              both upregulation and downregulation", "mrnas.

              both upregulation and downregulation of", "upregulation and downregulation of cdh19", "and downregulation of cdh19 have", "downregulation of cdh19 have been", "of cdh19 have been reported", "cdh19 have been reported in", "have been reported in cancer", "been reported in cancer and", "reported in cancer and it", "in cancer and it has", "cancer and it has been", "and it has been proposed", "it has been proposed to", "has been proposed to play", "been proposed to play both", "proposed to play both oncogenic", "to play both oncogenic and", "play both oncogenic and tumor", "both oncogenic and tumor suppressive", "oncogenic and tumor suppressive roles", "tumor suppressive roles depending", "suppressive roles depending on", "roles depending on the", "depending on the cancer type.", "on the cancer type. cdh19", "the cancer type. cdh19 mrna", "cancer type. cdh19 mrna is", "type. cdh19 mrna is upregulated", "cdh19 mrna is upregulated in", "mrna is upregulated in clear", "is upregulated in clear cell", "upregulated in clear cell sarcoma", "in clear cell sarcoma and", "clear cell sarcoma and correlates", "cell sarcoma and correlates with", "sarcoma and correlates with a", "and correlates with a hypomethylated", "correlates with a hypomethylated profile", "a hypomethylated profile dermawan", "hypomethylated profile dermawan et", "profile dermawan et al.", "dermawan et al. 2022 .", "et al. 2022 . in", "al. 2022 . in glioblastoma", ". in glioblastoma cdh19", "in glioblastoma cdh19 is", "glioblastoma cdh19 is upregulated", "cdh19 is upregulated in cancer", "is upregulated in cancer stem", "upregulated in cancer stem like", "in cancer stem like cells", "stem like cells zorniak", "like cells zorniak et", "cells zorniak et al.", "zorniak et al. 2015 .", "et al. 2015 . in", "al. 2015 . in colorectal", "2015 . in colorectal tumors", "in colorectal tumors cdh19", "colorectal tumors cdh19 is", "tumors cdh19 is upregulated", "cdh19 is upregulated compared to", "is upregulated compared to normal", "upregulated compared to normal tissue", "to normal tissue bujko", "normal tissue bujko et", "tissue bujko et al.", "bujko et al. 2015 .", "et al. 2015 . downregulation", "al. 2015 . downregulation of", "2015 . downregulation of cdh19", ". downregulation of cdh19 is", "downregulation of cdh19 is an", "of cdh19 is an independent", "cdh19 is an independent prognostic", "is an independent prognostic biomarker", "an independent prognostic biomarker of", "independent prognostic biomarker of the", "prognostic biomarker of the outcome", "biomarker of the outcome of", "of the outcome of lung", "the outcome of lung adenocarcinoma", "of lung adenocarcinoma li", "lung adenocarcinoma li et", "adenocarcinoma li et al.", "li et al. 2022 .", "al. 2022 . in triple", "2022 . in triple negative", ". in triple negative breast", "in triple negative breast cancer", "negative breast cancer cdh19", "breast cancer cdh19 was", "cancer cdh19 was proposed", "cdh19 was proposed to play", "was proposed to play a", "proposed to play a tumor", "to play a tumor suppressor", "play a tumor suppressor role", "tumor suppressor role shi", "suppressor role shi et", "role shi et al.", "et al. 2021 . a", "al. 2021 . a homozygous", "2021 . a homozygous deletion", ". a homozygous deletion of", "a homozygous deletion of the", "homozygous deletion of the cdh19", "deletion of the cdh19 gene", "of the cdh19 gene was", "the cdh19 gene was reported", "cdh19 gene was reported in", "gene was reported in a", "was reported in a portion", "reported in a portion of", "in a portion of chondrosarcoma", "a portion of chondrosarcoma tumor", "portion of chondrosarcoma tumor samples", "chondrosarcoma tumor samples niini", "tumor samples niini et", "samples niini et al.", "niini et al. 2012 ." ] }, { "record_id": "GLY_000594_1_2116", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9827857", "r hsa", "hsa 9827857", "r hsa 9827857" ] }, { 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"ectoderm and", "and wnt3", "wnt3 from", "from the", "the visceral", "visceral endoderm", "reviewed in", "in bleckwehl", "bleckwehl and", "and rada", "rada iglesias", "iglesias 2019", "2019 .", ". less", "less is", "is known", "known about", "about the", "the developmental", "developmental origin", "origin of", "of human", "human pgcs", "pgcs and", "and the", "the sources", "sources of", "of inducing", "inducing signaling", "signaling factors.", "factors. in", "the non", "non human", "human primate", "cynomolgus monkey", "are first", "first observed", "observed in", "the amniotic", "amniotic epithelium", "amniotic sac", "sac of", "the pre", "pre gastrulation", "gastrulation embryo", "embryo and", "and remain", "remain in", "the early", "early amnion", "amnion for", "for an", "an extended", "extended period", "6 days", "sasaki et", "al. 2016", "2016 .", ". bmp4", "bmp4 is", "is expressed", "expressed in", "the amnion", "amnion and", "and wnt3a", "wnt3a is", "the cytotrophoblast", "2016 .
              ex", ".
              ex vivo", "vivo and", "and in", "in vitro", "vitro studies", "studies have", "have been", "been performed", "performed to", "to elucidate", "elucidate the", "the specification", "in hancock", "hancock et", "al. 2021", "2021 .", ". putative", "putative pgcs", "identified by", "by immunofluorescence", "immunofluorescence of", "of pgc", "pgc markers", "induced in", "in ex", "ex vivo", "vivo culture", "culture of", "of early", "early blastocysts", "e6 days", "days post", "post fertilization", "chen et", "al. 2019", "popovic et", "vitro differentiation", "differentiation of", "of embryonic", "embryonic stem", "stem cells", "or induced", "induced pluripotent", "pluripotent stem", "the presence", "presence of", "of bmp4", "irie et", "al. 2015", "tang et", "al. 2017", "kojima et", "2017 .", ". in", "in both", "both mouse", "embryos and", "and cultured", "cultured human", "human cells", "competence of", "the epiblast", "epiblast like", "like cells", "cells to", "to form", "form pgcs", "pgcs in", "in response", "response to", "to bmp4", "bmp4 signals", "signals is", "is transient", "transient during", "during development", "the absence", "absence of", "cells acquire", "acquire the", "the mesendoderm", "mesendoderm cell", "cell fate", "2015 .
              for", ".
              for the", "the induction", "induction of", "pgc like", "cells from", "from human", "human pluripotent", "the gene", "gene network", "network activity", "activity that", "that specifies", "specifies human", "pgcs is", "is different", "different from", "from that", "that of", "of mouse", "mouse pgcs.", "pgcs. notably", "but not", "not prdm14", "is a", "a key", "key factor", "factor for", "for the", "human pgcs.", "pgcs. in", "in human", "human pgc", "pgc precursors", "activates expression", "expression of", "of sox17", "the most", "most upstream", "upstream factor", "factor in", "in pgc", "pgc specification.", "specification. similar", "similar molecular", "molecular events", "events are", "are observed", "early pgcs", "pgcs isolated", "isolated from", "human embryos", "and cynomolgus", "cynomolgus monkeys", "tyser et", "bmp4 signaling", "signaling initiates", "initiates the", "the expression", "of tfap2c", "tfap2c and", "and sox17", "that in", "in turns", "turns initiates", "initiates expression", "of prdm1", "al. 2022", "2022 .", ". together", "together these", "these three", "three key", "key factors", "and prdm1", "specify pgcs", "activate the", "the pgc", "pgc program", "and repress", "repress somatic", "somatic cell", "cell programs", "with sox17", "sox17 acting", "acting as", "as an", "an activator", "activator and", "prdm1 as", "as a", "a repressor", "2015 .", ". genes", "genes activated", "activated in", "in pgcs", "pgcs include", "include the", "the pluripotency", "pluripotency related", "related factors", "factors pou5f1", "and nanog", "not sox2", "the dna", "dna demethylation", "demethylation factor", "factor tet2", "the regulators", "regulators of", "of cell", "cell migration", "migration pdpn", "pdpn and", "and cxcr4", "al. 2018", "mishra et", ". prdm1", "prdm1 represses", "represses genes", "genes involved", "involved in", "in dna", "dna methylation", "methylation leading", "leading to", "to a", "a genome", "genome wide", "wide 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1994 .", "1994 . subsequently", "subsequently pgcs", "pgcs are regionalised", "are regionalised in", "regionalised in the", "in the epithelium", "the epithelium of", "epithelium of the", "of the embryonic", "the embryonic gut", "embryonic gut and", "gut and migrate", "and migrate via", "migrate via the", "via the dorsal", "the dorsal mesentery", "dorsal mesentery of", "mesentery of the", "embryonic gut to", "gut to the", "to the genital", "the genital ridge.", "genital ridge. the", "ridge. the post", "the post migratory", "post migratory pgcs", "migratory pgcs differentiate", "pgcs differentiate into", "differentiate into oogonia", "into oogonia and", "oogonia and spermatogonia", "and spermatogonia in", "spermatogonia in the", "in the fetal", "the fetal gonad.", "fetal gonad. in", "gonad. in mouse", "in mouse embryos", "embryos pgcs", "pgcs are induced", "are induced by", "induced by bmp4", "by bmp4 emanating", "bmp4 emanating from", "emanating from extraembryonic", "from 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"of the pre", "the pre gastrulation", "pre gastrulation embryo", "gastrulation embryo and", "embryo and remain", "and remain in", "remain in the", "in the early", "the early amnion", "early amnion for", "amnion for an", "for an extended", "an extended period", "period 6", "sasaki et al.", "et al. 2016", "al. 2016 .", "2016 . bmp4", ". bmp4 is", "bmp4 is expressed", "is expressed in", "expressed in the", "in the amnion", "the amnion and", "amnion and wnt3a", "and wnt3a is", "wnt3a is expressed", "in the cytotrophoblast", "cytotrophoblast sasaki", "al. 2016 .
              ex", "2016 .
              ex vivo", ".
              ex vivo and", "vivo and in", "and in vitro", "in vitro studies", "vitro studies have", "studies have been", "have been performed", "been performed to", "performed to elucidate", "to elucidate the", "elucidate the specification", "the specification of", "specification of human", "pgcs reviewed", "reviewed in hancock", "in hancock et", "hancock et al.", "et al. 2021", "al. 2021 .", "2021 . putative", ". putative pgcs", "pgcs identified", "identified by immunofluorescence", "by immunofluorescence of", "immunofluorescence of pgc", "of pgc markers", "markers are", "are induced in", "induced in ex", "in ex vivo", "ex vivo culture", "vivo culture of", "culture of early", "of early blastocysts", "blastocysts e6", "e6 days post", "days post fertilization", "fertilization dpf", "chen et al.", "et al. 2019", "2019 popovic", "popovic et al.", "2019 and", "in vitro differentiation", "vitro differentiation of", "differentiation of embryonic", "of embryonic stem", "embryonic stem cells", "cells escs", "escs or", "or induced pluripotent", "induced pluripotent stem", "pluripotent stem cells", "cells ipscs", "ipscs in", "in the presence", "the presence of", "presence of bmp4", "bmp4 irie", "irie et al.", "et al. 2015", "2015 sasaki", "2015 tang", "tang et al.", "2015 chen", "et al. 2017", "2017 kojima", "kojima et al.", "al. 2017 .", "2017 . in", ". in both", "in both mouse", "both mouse embryos", "mouse embryos and", "embryos and cultured", "and cultured human", "cultured human cells", "cells competence", "competence of the", "of the epiblast", "the epiblast like", "epiblast like cells", "like cells to", "cells to form", "to form pgcs", "form pgcs in", "pgcs in response", "in response to", "response to bmp4", "to bmp4 signals", "bmp4 signals is", "signals is transient", "is transient during", "transient during development", "development where", "where in", "in the absence", "the absence of", "absence of bmp4", "bmp4 the", "like cells acquire", "cells acquire the", "acquire the mesendoderm", "the mesendoderm cell", "mesendoderm cell fate", "fate tang", "al. 2015 .
              for", "2015 .
              for the", ".
              for the induction", "the induction of", "induction of pgc", "of pgc like", "pgc like cells", "like cells from", "cells from human", "from human pluripotent", "human pluripotent stem", "cells the", "the gene network", "gene network activity", "network activity that", "activity that specifies", "that specifies human", "specifies human pgcs", "human pgcs is", "pgcs is different", "is different from", "different from that", "from that of", "that of mouse", "of mouse pgcs.", "mouse pgcs. notably", "notably sox17", "sox17 but", "but not prdm14", "prdm14 is", "is a key", "a key factor", "key factor for", "factor for the", "for the specification", "of human pgcs.", "human pgcs. in", "pgcs. in human", "in human pgc", "human pgc precursors", "precursors eomesodermin", "eomesodermin eomes", "eomes activates", "activates expression of", "expression of sox17", "sox17 the", "the most upstream", "most upstream factor", "upstream factor in", "factor in pgc", "in pgc specification.", "pgc specification. similar", "specification. similar molecular", "similar molecular events", "molecular events are", "events are observed", "are observed in", "the early pgcs", "early pgcs isolated", "pgcs isolated from", "isolated from human", "from human embryos", "human embryos and", "embryos and cynomolgus", "and cynomolgus monkeys", "monkeys tyser", "tyser et al.", "2021 . bmp4", ". bmp4 signaling", "bmp4 signaling initiates", "signaling initiates the", "initiates the expression", "the expression of", "expression of tfap2c", "of tfap2c and", "tfap2c and sox17", "sox17 that", "that in turns", "in turns initiates", "turns initiates expression", "initiates expression of", "expression of prdm1", "prdm1 tang", "2015 kojima", "2017 tang", "et al. 2022", "al. 2022 .", "2022 . together", ". together these", "together these three", "these three key", "three key factors", "factors sox17", "sox17 tfap2c", "prdm1 specify", "pgcs activate", "activate the pgc", "the pgc program", "program and", "and repress somatic", "repress somatic cell", "somatic cell programs", "programs with", "with sox17 acting", "sox17 acting as", "acting as an", "as an activator", "an activator and", "activator and prdm1", "and prdm1 as", "prdm1 as a", "as a repressor", "repressor tang", "al. 2015 .", "2015 . genes", ". genes activated", "genes activated in", "activated in pgcs", "in pgcs include", "pgcs include the", "include the pluripotency", "the pluripotency related", "pluripotency related factors", "related factors pou5f1", "pou5f1 oct4", "oct4 and", "nanog but", "but not sox2", "the dna demethylation", "dna demethylation factor", "demethylation factor tet2", "tet2 and", "and the regulators", "the regulators of", "regulators of cell", "of cell migration", "cell migration pdpn", "migration pdpn and", "pdpn and cxcr4", "cxcr4 irie", "et al. 2018", "2018 mishra", "mishra et al.", "2021 tang", "2022 . prdm1", ". prdm1 represses", "prdm1 represses genes", "represses genes involved", "genes involved in", "involved in dna", "in dna methylation", "dna methylation leading", "methylation leading to", "leading to a", "to a genome", "a genome wide", "genome wide dna", "wide dna demethylation", "dna demethylation in", "demethylation in human", "in human pgcs", "human pgcs around", "pgcs around week", "around week 10", "week 10 11", "10 11 of", "11 of development", "development guo", "guo et al.", "2015 . in", ". in mouse", "in mouse embryonal", "mouse embryonal carcinoma", "embryonal carcinoma cells", "cells prdm1", "prdm1 blimp1", "blimp1 binds", "binds and represses", "and represses expression", "represses expression of", "expression of the", "of the de", "the de novo", "de novo dna", "novo dna methylase", "dna methylase dnmt3b", "methylase dnmt3b and", "dnmt3b and uhrf1", "uhrf1 which", "which interacts with", "interacts with the", "with the dna", "the dna methylase", "dna methylase dnmt1", "dnmt1 magnusdottir", "magnusdottir et al.", "et al. 2013", "al. 2013 .", "2013 . prdm1", ". prdm1 in", "prdm1 in human", "human pgcs similarly", "pgcs similarly represses", "similarly represses expression", "expression of dnmt3b", "dnmt3b dnmt1", "dnmt1 and", "and uhrf1 through", "uhrf1 through yet", "through yet uncharacterized", "yet uncharacterized mechanisms", "mechanisms tang", "germ cells pgcs", "pgcs the", "the progenitors of female", "progenitors of female gametes", "female gametes oocytes", "oocytes and male", "male gametes sperm", "sperm are", "are specified and segregated", "specified and segregated from", "and segregated from somatic", "segregated from somatic cells", "from somatic cells early", "somatic cells early during", "cells early during mammalian", "early during mammalian development.", "during mammalian development. in", "mammalian development. in the", "development. in the mouse", "in the mouse embryo", "mouse embryo precursors", "embryo precursors of", "precursors of pgcs are", "of pgcs are present", "pgcs are present in", "are present in the", "present in the proximal", "in the proximal epiblast", "the proximal epiblast adjacent", "proximal epiblast adjacent to", "epiblast adjacent to the", "adjacent to the extraembryonic", "to the extraembryonic ectoderm", "the extraembryonic ectoderm before", "extraembryonic ectoderm before gastrulation", "before gastrulation e6.0", "e6.0 pre streak", "streak stage and", "stage and pgcs", "and pgcs marked", "pgcs marked by", "marked by high alkaline", "by high alkaline phosphatase", "high alkaline phosphatase activity", "phosphatase activity ginsburg", "activity ginsburg et", "ginsburg et al. 1990", "1990 are", "are translocated to the", "translocated to the extraembryonic", "to the extraembryonic mesoderm", "the extraembryonic mesoderm at", "extraembryonic mesoderm at the", "mesoderm at the base", "at the base of", "the base of the", "base of the developing", "of the developing allantois", "the developing allantois during", "developing allantois during gastrulation", "during gastrulation lawson", "gastrulation lawson and", "lawson and hage 1994", "and hage 1994 .", "hage 1994 . subsequently", ". subsequently pgcs", "subsequently pgcs are", "pgcs are regionalised in", "are regionalised in the", "regionalised in the epithelium", "in the epithelium of", "the epithelium of the", "epithelium of the embryonic", "of the embryonic gut", "the embryonic gut and", "embryonic gut and migrate", "gut and migrate via", "and migrate via the", "migrate via the dorsal", "via the dorsal mesentery", "the dorsal mesentery of", "dorsal mesentery of the", "mesentery of the embryonic", "the embryonic gut to", "embryonic gut to the", "gut to the genital", "to the genital ridge.", "the genital ridge. the", "genital ridge. the post", "ridge. the post migratory", "the post migratory pgcs", "post migratory pgcs differentiate", "migratory pgcs differentiate into", "pgcs differentiate into oogonia", "differentiate into oogonia and", "into oogonia and spermatogonia", "oogonia and spermatogonia in", "and spermatogonia in the", "spermatogonia in the fetal", "in the fetal gonad.", "the fetal gonad. in", "fetal gonad. in mouse", "gonad. in mouse embryos", "mouse embryos pgcs", "embryos pgcs are", "pgcs are induced by", "are induced by bmp4", "induced by bmp4 emanating", "by bmp4 emanating from", "bmp4 emanating from extraembryonic", "emanating from extraembryonic ectoderm", "from extraembryonic ectoderm and", "extraembryonic ectoderm and wnt3", "ectoderm and wnt3 from", "and wnt3 from the", "wnt3 from the visceral", "from the visceral endoderm", "visceral endoderm reviewed", "endoderm reviewed in", "reviewed in bleckwehl and", "in bleckwehl and rada", "bleckwehl and rada iglesias", "and rada iglesias 2019", "rada iglesias 2019 .", "iglesias 2019 . less", "2019 . less is", ". less is known", "less is known about", "is known about the", "known about the developmental", "about the developmental origin", "the developmental origin of", "developmental origin of human", "origin of human pgcs", "of human pgcs and", "human pgcs and the", "pgcs and the sources", "and the sources of", "the sources of inducing", "sources of inducing signaling", "of inducing signaling factors.", "inducing signaling factors. in", "signaling factors. in the", "factors. in the non", "in the non human", "the non human primate", "human primate cynomolgus", "primate cynomolgus monkey", "monkey pgcs", "pgcs are first observed", "are first observed in", "first observed in the", "observed in the amniotic", "in the amniotic epithelium", "the amniotic epithelium of", "amniotic epithelium of the", "epithelium of the amniotic", "of the amniotic sac", "the amniotic sac of", "amniotic sac of the", "sac of the pre", "of the pre gastrulation", "the pre gastrulation embryo", "pre gastrulation embryo and", "gastrulation embryo and remain", "embryo and remain in", "and remain in the", "remain in the early", "in the early amnion", "the early amnion for", "early amnion for an", "amnion for an extended", "for an extended period", "extended period 6", "period 6 days", "days sasaki", "sasaki et al. 2016", "et al. 2016 .", "al. 2016 . bmp4", "2016 . bmp4 is", ". bmp4 is expressed", "bmp4 is expressed in", "is expressed in the", "expressed in the amnion", "in the amnion and", "the amnion and wnt3a", "amnion and wnt3a is", "and wnt3a is expressed", "wnt3a is expressed in", "expressed in the cytotrophoblast", "the cytotrophoblast sasaki", "cytotrophoblast sasaki et", "et al. 2016 .
              ex", "al. 2016 .
              ex vivo", "2016 .
              ex vivo and", ".
              ex vivo and in", "vivo and in vitro", "and in vitro studies", "in vitro studies have", "vitro studies have been", "studies have been performed", "have been performed to", "been performed to elucidate", "performed to elucidate the", "to elucidate the specification", "elucidate the specification of", "the specification of human", "specification of human pgcs", "human pgcs reviewed", "pgcs reviewed in", "reviewed in hancock et", "in hancock et al.", "hancock et al. 2021", "et al. 2021 .", "al. 2021 . putative", "2021 . putative pgcs", "putative pgcs identified", "pgcs identified by", "identified by immunofluorescence of", "by immunofluorescence of pgc", "immunofluorescence of pgc markers", "pgc markers are", "markers are induced", "are induced in ex", "induced in ex vivo", "in ex vivo culture", "ex vivo culture of", "vivo culture of early", "culture of early blastocysts", "early blastocysts e6", "blastocysts e6 days", "e6 days post fertilization", "post fertilization dpf", "dpf chen", "chen et al. 2019", "al. 2019 popovic", "2019 popovic et", "popovic et al. 2019", "al. 2019 and", "2019 and in", "and in vitro differentiation", "in vitro differentiation of", "vitro differentiation of embryonic", "differentiation of embryonic stem", "of embryonic stem cells", "stem cells escs", "escs or induced", "or induced pluripotent stem", "induced pluripotent stem cells", "stem cells ipscs", "ipscs in the", "in the presence of", "the presence of bmp4", "of bmp4 irie", "bmp4 irie et", "irie et al. 2015", "al. 2015 sasaki", "2015 sasaki et", "sasaki et al. 2015", "al. 2015 tang", "2015 tang et", "tang et al. 2015", "al. 2015 chen", "2015 chen et", "chen et al. 2017", "al. 2017 kojima", "2017 kojima et", "kojima et al. 2017", "et al. 2017 .", "al. 2017 . in", "2017 . in both", ". in both mouse", "in both mouse embryos", "both mouse embryos and", "mouse embryos and cultured", "embryos and cultured human", "and cultured human cells", "human cells competence", "cells competence of", "competence of the epiblast", "of the epiblast like", "the epiblast like cells", "epiblast like cells to", "like cells to form", "cells to form pgcs", "to form pgcs in", "form pgcs in response", "pgcs in response to", "in response to bmp4", "response to bmp4 signals", "to bmp4 signals is", "bmp4 signals is transient", "signals is transient during", "is transient during development", "during development where", "where in the", "in the absence of", "the absence of bmp4", "of bmp4 the", "bmp4 the epiblast", "epiblast like cells acquire", "like cells acquire the", "cells acquire the mesendoderm", "acquire the mesendoderm cell", "the mesendoderm cell fate", "cell fate tang", "fate tang et", "et al. 2015 .
              for", "al. 2015 .
              for the", "2015 .
              for the induction", ".
              for the induction of", "the induction of pgc", "induction of pgc like", "of pgc like cells", "pgc like cells from", "like cells from human", "cells from human pluripotent", "from human pluripotent stem", "human pluripotent stem cells", "stem cells the", "cells the gene", "the gene network activity", "gene network activity that", "network activity that specifies", "activity that specifies human", "that specifies human pgcs", "specifies human pgcs is", "human pgcs is different", "pgcs is different from", "is different from that", "different from that of", "from that of mouse", "that of mouse pgcs.", "of mouse pgcs. notably", "pgcs. notably sox17", "sox17 but not", "not prdm14 is", "prdm14 is a", "is a key factor", "a key factor for", "key factor for the", "factor for the specification", "for the specification of", "specification of human pgcs.", "of human pgcs. in", "human pgcs. in human", "pgcs. in human pgc", "in human pgc precursors", "pgc precursors eomesodermin", "eomes activates expression", "activates expression of sox17", "of sox17 the", "sox17 the most", "the most upstream factor", "most upstream factor in", "upstream factor in pgc", "factor in pgc specification.", "in pgc specification. similar", "pgc specification. similar molecular", "specification. similar molecular events", "similar molecular events are", "molecular events are observed", "events are observed in", "are observed in the", "observed in the early", "in the early pgcs", "the early pgcs isolated", "early pgcs isolated from", "pgcs isolated from human", "isolated from human embryos", "from human embryos and", "human embryos and cynomolgus", "embryos and cynomolgus monkeys", "cynomolgus monkeys tyser", "monkeys tyser et", "tyser et al. 2021", "al. 2021 . bmp4", "2021 . bmp4 signaling", ". bmp4 signaling initiates", "bmp4 signaling initiates the", "signaling initiates the expression", "initiates the expression of", "the expression of tfap2c", "expression of tfap2c and", "of tfap2c and sox17", "and sox17 that", "sox17 that in", "that in turns initiates", "in turns initiates expression", "turns initiates expression of", "initiates expression of prdm1", "of prdm1 tang", "prdm1 tang et", "al. 2015 kojima", "2015 kojima et", "al. 2017 tang", "2017 tang et", "tang et al. 2022", "et al. 2022 .", "al. 2022 . together", "2022 . together these", ". together these three", "together these three key", "these three key factors", "key factors sox17", "tfap2c and prdm1", "and prdm1 specify", "prdm1 specify pgcs", "specify pgcs activate", "pgcs activate the", "activate the pgc program", "pgc program and", "program and repress", "and repress somatic cell", "repress somatic cell programs", "cell programs with", "programs with sox17", "with sox17 acting as", "sox17 acting as an", "acting as an activator", "as an activator and", "an activator and prdm1", "activator and prdm1 as", "and prdm1 as a", "prdm1 as a repressor", "a repressor tang", "repressor tang et", "et al. 2015 .", "al. 2015 . genes", "2015 . genes activated", ". genes activated in", "genes activated in pgcs", "activated in pgcs include", "in pgcs include the", "pgcs include the pluripotency", "include the pluripotency related", "the pluripotency related factors", "pluripotency related factors pou5f1", "factors pou5f1 oct4", "oct4 and nanog", "and nanog but", "nanog but not", "sox2 the", "the dna demethylation factor", "dna demethylation factor tet2", "factor tet2 and", "tet2 and the", "and the regulators of", "the regulators of cell", "regulators of cell migration", "of cell migration pdpn", "cell migration pdpn and", "migration pdpn and cxcr4", "and cxcr4 irie", "cxcr4 irie et", "chen et al. 2018", "al. 2018 mishra", "2018 mishra et", "mishra et al. 2021", "al. 2021 tang", "2021 tang et", "al. 2022 . prdm1", "2022 . prdm1 represses", ". prdm1 represses genes", "prdm1 represses genes involved", "represses genes involved in", "genes involved in dna", "involved in dna methylation", "in dna methylation leading", "dna methylation leading to", "methylation leading to a", "leading to a genome", "to a genome wide", "a genome wide dna", "genome wide dna demethylation", "wide dna demethylation in", "dna demethylation in human", "demethylation in human pgcs", "in human pgcs around", "human pgcs around week", "pgcs around week 10", "around week 10 11", "week 10 11 of", "10 11 of development", "of development guo", "development guo et", "guo et al. 2015", "al. 2015 . in", "2015 . in mouse", ". in mouse embryonal", "in mouse embryonal carcinoma", "mouse embryonal carcinoma cells", "carcinoma cells prdm1", "blimp1 binds and", "binds and represses expression", "and represses expression of", "represses expression of the", "expression of the de", "of the de novo", "the de novo dna", "de novo dna methylase", "novo dna methylase dnmt3b", "dna methylase dnmt3b and", "methylase dnmt3b and uhrf1", "and uhrf1 which", "uhrf1 which interacts", "which interacts with the", "interacts with the dna", "with the dna methylase", "the dna methylase dnmt1", "methylase dnmt1 magnusdottir", "dnmt1 magnusdottir et", "magnusdottir et al. 2013", "et al. 2013 .", "al. 2013 . prdm1", "2013 . prdm1 in", ". prdm1 in human", "prdm1 in human pgcs", "in human pgcs similarly", "human pgcs similarly represses", "pgcs similarly represses expression", "similarly represses expression of", "represses expression of dnmt3b", "of dnmt3b dnmt1", "dnmt1 and uhrf1", "and uhrf1 through yet", "uhrf1 through yet uncharacterized", "through yet uncharacterized mechanisms", "uncharacterized mechanisms tang", "mechanisms tang et", "primordial germ cells pgcs", "pgcs the progenitors", "the progenitors of female gametes", "of female gametes oocytes", "gametes oocytes and", "oocytes and male gametes", "and male gametes sperm", "sperm are specified", "are specified and segregated from", "specified and segregated from somatic", "and segregated from somatic cells", "segregated from somatic cells early", "from somatic cells early during", "somatic cells early during mammalian", "cells early during mammalian development.", "early during mammalian development. in", "during mammalian development. in the", "mammalian development. in the mouse", "development. in the mouse embryo", "the mouse embryo precursors", "mouse embryo precursors of", "embryo precursors of pgcs", "precursors of pgcs are present", "of pgcs are present in", "pgcs are present in the", "are present in the proximal", "present in the proximal epiblast", "in the proximal epiblast adjacent", "the proximal epiblast adjacent to", "proximal epiblast adjacent to the", "epiblast adjacent to the extraembryonic", "adjacent to the extraembryonic ectoderm", "to the extraembryonic ectoderm before", "the extraembryonic ectoderm before gastrulation", "ectoderm before gastrulation e6.0", "gastrulation e6.0 pre", "e6.0 pre streak stage", "pre streak stage and", "streak stage and pgcs", "and pgcs marked by", "pgcs marked by high", "marked by high alkaline phosphatase", "by high alkaline phosphatase activity", "alkaline phosphatase activity ginsburg", "phosphatase activity ginsburg et", "activity ginsburg et al.", "al. 1990 are", "1990 are translocated", "are translocated to the extraembryonic", "translocated to the extraembryonic mesoderm", "to the extraembryonic mesoderm at", "the extraembryonic mesoderm at the", "extraembryonic mesoderm at the base", "mesoderm at the base of", "at the base of the", "the base of the developing", "base of the developing allantois", "of the developing allantois during", "the developing allantois during gastrulation", "allantois during gastrulation lawson", "during gastrulation lawson and", "gastrulation lawson and hage", "lawson and hage 1994 .", "and hage 1994 . subsequently", "1994 . subsequently pgcs", ". subsequently pgcs are", "subsequently pgcs are regionalised", "pgcs are regionalised in the", "are regionalised in the epithelium", "regionalised in the epithelium of", "in the epithelium of the", "the epithelium of the embryonic", "epithelium of the embryonic gut", "of the embryonic gut and", "the embryonic gut and migrate", "embryonic gut and migrate via", "gut and migrate via the", "and migrate via the dorsal", "migrate via the dorsal mesentery", "via the dorsal mesentery of", "the dorsal mesentery of the", "dorsal mesentery of the embryonic", "mesentery of the embryonic gut", "of the embryonic gut to", "the embryonic gut to the", "embryonic gut to the genital", "gut to the genital ridge.", "to the genital ridge. the", "the genital ridge. the post", "genital ridge. the post migratory", "ridge. the post migratory pgcs", "the post migratory pgcs differentiate", "post migratory pgcs differentiate into", "migratory pgcs differentiate into oogonia", "pgcs differentiate into oogonia and", "differentiate into oogonia and spermatogonia", "into oogonia and spermatogonia in", "oogonia and spermatogonia in the", "and spermatogonia in the fetal", "spermatogonia in the fetal gonad.", "in the fetal gonad. in", "the fetal gonad. in mouse", "fetal gonad. in mouse embryos", "in mouse embryos pgcs", "mouse embryos pgcs are", "embryos pgcs are induced", "pgcs are induced by bmp4", "are induced by bmp4 emanating", "induced by bmp4 emanating from", "by bmp4 emanating from extraembryonic", "bmp4 emanating from extraembryonic ectoderm", "emanating from extraembryonic ectoderm and", "from extraembryonic ectoderm and wnt3", "extraembryonic ectoderm and wnt3 from", "ectoderm and wnt3 from the", "and wnt3 from the visceral", "wnt3 from the visceral endoderm", "the visceral endoderm reviewed", "visceral endoderm reviewed in", "endoderm reviewed in bleckwehl", "reviewed in bleckwehl and rada", "in bleckwehl and rada iglesias", "bleckwehl and rada iglesias 2019", "and rada iglesias 2019 .", "rada iglesias 2019 . less", "iglesias 2019 . less is", "2019 . less is known", ". less is known about", "less is known about the", "is known about the developmental", "known about the developmental origin", "about the developmental origin of", "the developmental origin of human", "developmental origin of human pgcs", "origin of human pgcs and", "of human pgcs and the", "human pgcs and the sources", "pgcs and the sources of", "and the sources of inducing", "the sources of inducing signaling", "sources of inducing signaling factors.", "of inducing signaling factors. in", "inducing signaling factors. in the", "signaling factors. in the non", "factors. in the non human", "in the non human primate", "non human primate cynomolgus", "human primate cynomolgus monkey", "cynomolgus monkey pgcs", "monkey pgcs are", "pgcs are first observed in", "are first observed in the", "first observed in the amniotic", "observed in the amniotic epithelium", "in the amniotic epithelium of", "the amniotic epithelium of the", "amniotic epithelium of the amniotic", "epithelium of the amniotic sac", "of the amniotic sac of", "the amniotic sac of the", "amniotic sac of the pre", "sac of the pre gastrulation", "of the pre gastrulation embryo", "the pre gastrulation embryo and", "pre gastrulation embryo and remain", "gastrulation embryo and remain in", "embryo and remain in the", "and remain in the early", "remain in the early amnion", "in the early amnion for", "the early amnion for an", "early amnion for an extended", "amnion for an extended period", "an extended period 6", "extended period 6 days", "6 days sasaki", "days sasaki et", "sasaki et al. 2016 .", "et al. 2016 . bmp4", "al. 2016 . bmp4 is", "2016 . bmp4 is expressed", ". bmp4 is expressed in", "bmp4 is expressed in the", "is expressed in the amnion", "expressed in the amnion and", "in the amnion and wnt3a", "the amnion and wnt3a is", "amnion and wnt3a is expressed", "and wnt3a is expressed in", "wnt3a is expressed in the", "is expressed in the cytotrophoblast", "in the cytotrophoblast sasaki", "the cytotrophoblast sasaki et", "cytotrophoblast sasaki et al.", "sasaki et al. 2016 .
              ex", "et al. 2016 .
              ex vivo", "al. 2016 .
              ex vivo and", "2016 .
              ex vivo and in", ".
              ex vivo and in vitro", "vivo and in vitro studies", "and in vitro studies have", "in vitro studies have been", "vitro studies have been performed", "studies have been performed to", "have been performed to elucidate", "been performed to elucidate the", "performed to elucidate the specification", "to elucidate the specification of", "elucidate the specification of human", "the specification of human pgcs", "of human pgcs reviewed", "human pgcs reviewed in", "pgcs reviewed in hancock", "reviewed in hancock et al.", "in hancock et al. 2021", "hancock et al. 2021 .", "et al. 2021 . putative", "al. 2021 . putative pgcs", ". putative pgcs identified", "putative pgcs identified by", "pgcs identified by immunofluorescence", "identified by immunofluorescence of pgc", "by immunofluorescence of pgc markers", "of pgc markers are", "pgc markers are induced", "markers are induced in", "are induced in ex vivo", "induced in ex vivo culture", "in ex vivo culture of", "ex vivo culture of early", "vivo culture of early blastocysts", "of early blastocysts e6", "early blastocysts e6 days", "blastocysts e6 days post", "days post fertilization dpf", "dpf chen et", "et al. 2019 popovic", "al. 2019 popovic et", "2019 popovic et al.", "et al. 2019 and", "al. 2019 and in", "2019 and in vitro", "and in vitro differentiation of", "in vitro differentiation of embryonic", "vitro differentiation of embryonic stem", "differentiation of embryonic stem cells", "embryonic stem cells escs", "cells escs or", "escs or induced pluripotent", "or induced pluripotent stem cells", "pluripotent stem cells ipscs", "cells ipscs in", "ipscs in the presence", "in the presence of bmp4", "presence of bmp4 irie", "of bmp4 irie et", "bmp4 irie et al.", "et al. 2015 sasaki", "al. 2015 sasaki et", "2015 sasaki et al.", "et al. 2015 tang", "al. 2015 tang et", "2015 tang et al.", "et al. 2015 chen", "al. 2015 chen et", "2015 chen et al.", "et al. 2017 kojima", "al. 2017 kojima et", "2017 kojima et al.", "kojima et al. 2017 .", "et al. 2017 . in", "al. 2017 . in both", "2017 . in both mouse", ". in both mouse embryos", "in both mouse embryos and", "both mouse embryos and cultured", "mouse embryos and cultured human", "embryos and cultured human cells", "cultured human cells competence", "human cells competence of", "cells competence of the", "competence of the epiblast like", "of the epiblast like cells", "the epiblast like cells to", "epiblast like cells to form", "like cells to form pgcs", "cells to form pgcs in", "to form pgcs in response", "form pgcs in response to", "pgcs in response to bmp4", "in response to bmp4 signals", "response to bmp4 signals is", "to bmp4 signals is transient", "bmp4 signals is transient during", "signals is transient during development", "transient during development where", "development where in", "where in the absence", "in the absence of bmp4", "absence of bmp4 the", "of bmp4 the epiblast", "bmp4 the epiblast like", "the epiblast like cells acquire", "epiblast like cells acquire the", "like cells acquire the mesendoderm", "cells acquire the mesendoderm cell", "acquire the mesendoderm cell fate", "mesendoderm cell fate tang", "cell fate tang et", "fate tang et al.", "tang et al. 2015 .
              for", "et al. 2015 .
              for the", "al. 2015 .
              for the induction", "2015 .
              for the induction of", ".
              for the induction of pgc", "the induction of pgc like", "induction of pgc like cells", "of pgc like cells from", "pgc like cells from human", "like cells from human pluripotent", "cells from human pluripotent stem", "from human pluripotent stem cells", "pluripotent stem cells the", "stem cells the gene", "cells the gene network", "the gene network activity that", "gene network activity that specifies", "network activity that specifies human", "activity that specifies human pgcs", "that specifies human pgcs is", "specifies human pgcs is different", "human pgcs is different from", "pgcs is different from that", "is different from that of", "different from that of mouse", "from that of mouse pgcs.", "that of mouse pgcs. notably", "mouse pgcs. notably sox17", "notably sox17 but", "sox17 but not prdm14", "but not prdm14 is", "not prdm14 is a", "prdm14 is a key", "is a key factor for", "a key factor for the", "key factor for the specification", "factor for the specification of", "for the specification of human", "the specification of human pgcs.", "specification of human pgcs. in", "of human pgcs. in human", "human pgcs. in human pgc", "pgcs. in human pgc precursors", "human pgc precursors eomesodermin", "precursors eomesodermin eomes", "eomesodermin eomes activates", "eomes activates expression of", "expression of sox17 the", "of sox17 the most", "sox17 the most upstream", "the most upstream factor in", "most upstream factor in pgc", "upstream factor in pgc specification.", "factor in pgc specification. similar", "in pgc specification. similar molecular", "pgc specification. similar molecular events", "specification. similar molecular events are", "similar molecular events are observed", "molecular events are observed in", "events are observed in the", "are observed in the early", "observed in the early pgcs", "in the early pgcs isolated", "the early pgcs isolated from", "early pgcs isolated from human", "pgcs isolated from human embryos", "isolated from human embryos and", "from human embryos and cynomolgus", "human embryos and cynomolgus monkeys", "and cynomolgus monkeys tyser", "cynomolgus monkeys tyser et", "monkeys tyser et al.", "tyser et al. 2021 .", "et al. 2021 . bmp4", "al. 2021 . bmp4 signaling", "2021 . bmp4 signaling initiates", ". bmp4 signaling initiates the", "bmp4 signaling initiates the expression", "signaling initiates the expression of", "initiates the expression of tfap2c", "the expression of tfap2c and", "expression of tfap2c and sox17", "tfap2c and sox17 that", "and sox17 that in", "sox17 that in turns", "that in turns initiates expression", "in turns initiates expression of", "turns initiates expression of prdm1", "expression of prdm1 tang", "of prdm1 tang et", "prdm1 tang et al.", "et al. 2015 kojima", "al. 2015 kojima et", "2015 kojima et al.", "et al. 2017 tang", "al. 2017 tang et", "2017 tang et al.", "tang et al. 2022 .", "et al. 2022 . together", "al. 2022 . together these", "2022 . together these three", ". together these three key", "together these three key factors", "three key factors sox17", "factors sox17 tfap2c", "sox17 tfap2c and", "and prdm1 specify pgcs", "specify pgcs activate the", "pgcs activate the pgc", "the pgc program and", "pgc program and repress", "program and repress somatic", "and repress somatic cell programs", "somatic cell programs with", "cell programs with sox17", "programs with sox17 acting", "with sox17 acting as an", "sox17 acting as an activator", "acting as an activator and", "as an activator and prdm1", "an activator and prdm1 as", "activator and prdm1 as a", "and prdm1 as a repressor", "as a repressor tang", "a repressor tang et", "repressor tang et al.", "sasaki et al. 2015 .", "et al. 2015 . genes", "al. 2015 . genes activated", "2015 . genes activated in", ". genes activated in pgcs", "genes activated in pgcs include", "activated in pgcs include the", "in pgcs include the pluripotency", "pgcs include the pluripotency related", "include the pluripotency related factors", "the pluripotency related factors pou5f1", "related factors pou5f1 oct4", "pou5f1 oct4 and", "and nanog but not", "nanog but not sox2", "not sox2 the", "sox2 the dna", "the dna demethylation factor tet2", "demethylation factor tet2 and", "factor tet2 and the", "tet2 and the regulators", "and the regulators of cell", "the regulators of cell migration", "regulators of cell migration pdpn", "of cell migration pdpn and", "cell migration pdpn and cxcr4", "pdpn and cxcr4 irie", "and cxcr4 irie et", "cxcr4 irie et al.", "et al. 2018 mishra", "al. 2018 mishra et", "2018 mishra et al.", "et al. 2021 tang", "al. 2021 tang et", "2021 tang et al.", "et al. 2022 . prdm1", "al. 2022 . prdm1 represses", "2022 . prdm1 represses genes", ". prdm1 represses genes involved", "prdm1 represses genes involved in", "represses genes involved in dna", "genes involved in dna methylation", "involved in dna methylation leading", "in dna methylation leading to", "dna methylation 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              in the", "the oocyte", "h3k9me2 produced", "produced by", "by ehmt2", "and h3k9me3", "h3k9me3 produced", "by setdb1", "are transmitted", "transmitted to", "the female", "female pronucleus", "pronucleus of", "the zygote", "zygote and", "and protect", "protect maternal", "maternal dna", "dna from", "from active", "active demethylation", "inferred from", "from mouse", "mouse zygotes", "zygotes in", "in zeng", "zeng et", "et al.", "al. 2019", "reviewed in", "in de", "de macedo", "macedo et", "al. 2021", "2021 .", ". dppa3", "dppa3 binds", "binds h3k9me2", "preventing the", "the 5", "5 methylcytosine", "methylcytosine oxidase", "oxidase tet3", "tet3 from", "from being", "being recruited", "recruited to", "to chromatin", "mouse homologs", "homologs in", "in nakamura", "nakamura et", "al. 2007", "wossidlo et", "al. 2011", "al. 2012", "2012 .", "dppa3 also", "also displaces", "displaces uhrf1", "uhrf1 from", "from chromatin", "the maintenance", "maintenance dna", "dna methylase", "methylase dnmt1", "dnmt1 from", "chromatin and", "and thus", "thus allowing", "allowing passive", "passive dna", "demethylation to", "to occur", "occur in", "female genome", "in funaki", "funaki et", "al. 2014", "li et", "al. 2018", "du et", "mulholland et", "al. 2020", "2020 .
              in", ".
              in the", "the male", "male pronucleus", "deaminates cytosine", "cytosine residues", "residues and", "and long", "long patch", "patch repair", "repair replaces", "replaces the", "the mismatches", "mismatches and", "and adjacent", "adjacent 5", "5 methylcytidine", "methylcytidine residues", "residues with", "with cytidine", "santos et", "al. 2013", "franchini et", "2014 .", ". after", "after this", "this initial", "initial demethylation", "tet3 is", "is recruited", "chromatin by", "by mettl23", "mettl23 and", "and stgp4", "in hatanaka", "hatanaka et", "al. 2017", "where it", "it oxidizes", "oxidizes remaining", "remaining 5", "methylcytidine to", "to 5", "5 hydroxymethylcytidine", "which is", "is removed", "removed by", "by base", "base excision", "excision repair", "repair and", "and replaced", "replaced with", "in gu", "gu et", "iqbal et", "amouroux et", "al. 2016", "2017 .
              the", ".
              the repressive", "repressive mark", "mark h3k27me3", "h3k27me3 decreases", "decreases in", "in 2", "2 cell", "cell embryos", "embryos near", "near developmentally", "developmentally related", "related genes", "xia et", "2019 .", ". the", "the h3k27me3", "h3k27me3 demethylases", "demethylases kdm6b", "from bovine", "bovine embryos", "embryos in", "in chung", "chung et", "canovas et", "and kdm6a", "mouse embryos", "in bai", "bai et", "appear to", "to play", "play a", "a role", "role in", "the decrease", "decrease of", "of h3k27me3", "as downregulation", "downregulation of", "of them", "them impairs", "impairs h3k27me3", "h3k27me3 loss", "zygotic genome", "genome activation", "and embryonic", "embryonic development.", "development. embryonic", "embryonic development", "development also", "also requires", "requires h3k36me3", "a permissive", "permissive mark", "mark located", "located in", "in transcribed", "transcribed gene", "gene bodies", "bodies that", "that is", "is produced", "produced in", "oocyte by", "by setd2", "in xu", "xu et", "2019 .
              in", ".
              in mouse", "mouse oocytes", "h3k4me3 occurs", "occurs in", "in unusually", "unusually broad", "broad regions", "regions that", "that span", "span genes", "genes dahl", "dahl et", "zhang et", "2016 .", ". these", "these broad", "regions persist", "persist in", "and into", "into the", "the 2", "cell stage.", "stage. in", "the late", "late 2", "cell stage", "stage the", "the more", "more usual", "usual patterns", "patterns of", "of h3k4me3", "h3k4me3 are", "are established", "established as", "as sharp", "sharp peaks", "peaks of", "h3k4me3 near", "near the", "the transcription", "transcription start", "start sites", "sites and", "and stop", "stop sites", "sites of", "of genes.", "genes. the", "the histone", "histone methyltransferase", "methyltransferase kmt2b", "kmt2b is", "is at", "at least", "least partly", "partly responsible", "responsible for", "for establishing", "establishing the", "the broad", "regions of", "h3k4me3 in", "oocyte and", "and the", "histone demethylases", "demethylases kdm5b", "kdm5b and", "and kdm5a", "kdm5a remove", "remove the", "broad h3k4me3", "stage embryo", "in dahl", "in eckerseley", "eckerseley maslin", "maslin et", "2018 .
              in", ".
              in human", "human oocytes", "oocytes and", "and zygotes", "are not", "not observed", "observed across", "across genes", "genes but", "but are", "are located", "located across", "across distal", "cpg rich", "rich domains", "domains which", "which have", "have partial", "partial dna", ". at", "at the", "the 8", "8 cell", "expression of", "of kdm5b", "kdm5b increases", "increases and", "the h3k4me3", "h3k4me3 at", "the distal", "distal domains", "domains is", "is lost", "lost as", "as zygotic", "activation occurs", "suggesting a", "role for", "for kdm5b", "kdm5b in", "in loss", "loss of", "chromatin in the", "in the zygotic", "the zygotic pronuclei", "zygotic pronuclei transitions", "pronuclei transitions to", "transitions to a", "to a more", "a more open", "more open and", "open and accessible", "and accessible conformation", "accessible conformation by", "conformation by dna", "by dna demethylation", "dna demethylation and", "demethylation and changes", "and changes to", "changes to histone", "to histone modifications.", "histone modifications. as", "modifications. as development", "as development proceeds", "development proceeds through", "proceeds through the", "through the cleavage", "the cleavage stages", "cleavage stages to", "stages to the", "to the blastocyst", "blastocyst chromatin", "chromatin continues to", "continues to become", "to become more", "become more accessible", "more accessible until", "accessible until dna", "until dna methylation", "dna methylation and", "methylation and a", "and a more", "a more restrictive", "more restrictive chromatin", "restrictive chromatin conformation", "chromatin conformation are", "conformation are re", "are re established", "re established after", "established after implantation", "after implantation of", "implantation of the", "of the embryo", "the embryo in", "embryo in the", "in the uterus.
              in", "the uterus.
              in the", "uterus.
              in the oocyte", "oocyte h3k9me2", "h3k9me2 produced by", "produced by ehmt2", "ehmt2 g9a", "g9a kmt1c", "kmt1c and", "and h3k9me3 produced", "h3k9me3 produced by", "produced by setdb1", "setdb1 kmt1e", "kmt1e are", "are transmitted to", "transmitted to the", "to the female", "the female pronucleus", "female pronucleus of", "pronucleus of the", "of the zygote", "the zygote and", "zygote and protect", "and protect maternal", "protect maternal dna", "maternal dna from", "dna from active", "from active demethylation", "demethylation inferred", "inferred from mouse", "from mouse zygotes", "mouse zygotes in", "zygotes in zeng", "in zeng et", "zeng et al.", "et al. 2019", "2019 reviewed", "reviewed in de", "in de macedo", "de macedo et", "macedo et al.", "et al. 2021", "al. 2021 .", "2021 . dppa3", ". dppa3 binds", "dppa3 binds h3k9me2", "h3k9me2 preventing", "preventing the 5", "the 5 methylcytosine", "5 methylcytosine oxidase", "methylcytosine oxidase tet3", "oxidase tet3 from", "tet3 from being", "from being recruited", "being recruited to", "recruited to chromatin", "chromatin inferred", "from mouse homologs", "mouse homologs in", "homologs in nakamura", "in nakamura et", "nakamura et al.", "et al. 2007", "2007 wossidlo", "wossidlo et al.", "et al. 2011", "2011 nakamura", "et al. 2012", "al. 2012 .", "2012 . dppa3", ". dppa3 also", "dppa3 also displaces", "also displaces uhrf1", "displaces uhrf1 from", "uhrf1 from chromatin", "chromatin preventing", "preventing the maintenance", "the maintenance dna", "maintenance dna methylase", "dna methylase dnmt1", "methylase dnmt1 from", "dnmt1 from being", "to chromatin and", "chromatin and thus", "and thus allowing", "thus allowing passive", "allowing passive dna", "passive dna demethylation", "dna demethylation to", "demethylation to occur", "to occur in", "occur in the", "in the female", "the female genome", "genome inferred", "homologs in funaki", "in funaki et", "funaki et al.", "et al. 2014", "2014 li", "li et al.", "et al. 2018", "2018 du", "du et al.", "2019 mulholland", "mulholland et al.", "et al. 2020", "al. 2020 .
              in", "2020 .
              in the", ".
              in the male", "the male pronucleus", "male pronucleus of", "zygote aicda", "aicda aid", "aid deaminates", "deaminates cytosine residues", "cytosine residues and", "residues and long", "and long patch", "long patch repair", "patch repair replaces", "repair replaces the", "replaces the mismatches", "the mismatches and", "mismatches and adjacent", "and adjacent 5", "adjacent 5 methylcytidine", "5 methylcytidine residues", "methylcytidine residues with", "residues with cytidine", "cytidine santos", "santos et al.", "et al. 2013", "2013 franchini", "franchini et al.", "al. 2014 .", "2014 . after", ". after this", "after this initial", "this initial demethylation", "demethylation tet3", "tet3 is recruited", "is recruited to", "to chromatin by", "chromatin by mettl23", "by mettl23 and", "mettl23 and stgp4", "stgp4 gse", "homologs in hatanaka", "in hatanaka et", "hatanaka et al.", "et al. 2017", "2017 where", "where it oxidizes", "it oxidizes remaining", "oxidizes remaining 5", "remaining 5 methylcytidine", "5 methylcytidine to", "methylcytidine to 5", "to 5 hydroxymethylcytidine", "hydroxymethylcytidine which", "which is removed", "is removed by", "removed by base", "by base excision", "base excision repair", "excision repair and", "repair and replaced", "and replaced with", "replaced with cytidine", "cytidine inferred", "homologs in gu", "in gu et", "gu et al.", "2011 iqbal", "iqbal et al.", "2011 wossidlo", "2011 santos", "2013 amouroux", "amouroux et al.", "et al. 2016", "2016 hatanaka", "al. 2017 .
              the", "2017 .
              the repressive", ".
              the repressive mark", "repressive mark h3k27me3", "mark h3k27me3 decreases", "h3k27me3 decreases in", "decreases in 2", "in 2 cell", "2 cell embryos", "cell embryos near", "embryos near developmentally", "near developmentally related", "developmentally related genes", "genes xia", "xia et al.", "al. 2019 .", "2019 . the", ". the h3k27me3", "the h3k27me3 demethylases", "h3k27me3 demethylases kdm6b", "kdm6b inferred", "inferred from bovine", "from bovine embryos", "bovine embryos in", "embryos in chung", "in chung et", "chung et al.", "2017 canovas", "canovas et al.", "2012 and", "kdm6a inferred", "from mouse embryos", "mouse embryos in", "embryos in bai", "in bai et", "bai et al.", "2019 appear", "appear to play", "to play a", "play a role", "a role in", "role in the", "in the decrease", "the decrease of", "decrease of h3k27me3", "h3k27me3 as", "as downregulation of", "downregulation of them", "of them impairs", "them impairs h3k27me3", "impairs h3k27me3 loss", "loss zygotic", "zygotic genome activation", "activation and", "and embryonic development.", "embryonic development. embryonic", "development. embryonic development", "embryonic development also", "development also requires", "also requires h3k36me3", "h3k36me3 a", "a permissive mark", "permissive mark located", "mark located in", "located in transcribed", "in transcribed gene", "transcribed gene bodies", "gene bodies that", "bodies that is", "that is produced", "is produced in", "produced in the", "in the oocyte", "the oocyte by", "oocyte by setd2", "setd2 inferred", "embryos in xu", "in xu et", "xu et al.", "al. 2019 .
              in", "2019 .
              in mouse", ".
              in mouse oocytes", "oocytes h3k4me3", "h3k4me3 occurs in", "occurs in unusually", "in unusually broad", "unusually broad regions", "broad regions that", "regions that span", "that span genes", "span genes dahl", "genes dahl et", "dahl et al.", "2016 zhang", "zhang et al.", "al. 2016 .", "2016 . these", ". these broad", "these broad regions", "broad regions persist", "regions persist in", "persist in the", "in the zygote", "zygote and into", "and into the", "into the 2", "the 2 cell", "2 cell stage.", "cell stage. in", "stage. in the", "in the late", "the late 2", "late 2 cell", "2 cell stage", "cell stage the", "stage the more", "the more usual", "more usual patterns", "usual patterns of", "patterns of h3k4me3", "of h3k4me3 are", "h3k4me3 are established", "are established as", "established as sharp", "as sharp peaks", "sharp peaks of", "peaks of h3k4me3", "of h3k4me3 near", "h3k4me3 near the", "near the transcription", "the transcription start", "transcription start sites", "start sites and", "sites and stop", "and stop sites", "stop sites of", "sites of genes.", "of genes. the", "genes. the histone", "the histone methyltransferase", "histone methyltransferase kmt2b", "methyltransferase kmt2b is", "kmt2b is at", "is at least", "at least partly", "least partly responsible", "partly responsible for", "responsible for establishing", "for establishing the", "establishing the broad", "the broad regions", "broad regions of", "regions of h3k4me3", "of h3k4me3 in", "h3k4me3 in the", "the oocyte and", "oocyte and the", "and the histone", "the histone demethylases", "histone demethylases kdm5b", "demethylases kdm5b and", "kdm5b and kdm5a", "and kdm5a remove", "kdm5a remove the", "remove the broad", "the broad h3k4me3", "broad h3k4me3 in", "cell stage embryo", "embryo inferred", "homologs in dahl", "in dahl et", "2016 reviewed", "reviewed in eckerseley", "in eckerseley maslin", "eckerseley maslin et", "maslin et al.", "al. 2018 .
              in", "2018 .
              in human", ".
              in human oocytes", "human oocytes and", "oocytes and zygotes", "zygotes however", "however broad", "h3k4me3 are not", "are not observed", "not observed across", "observed across genes", "across genes but", "genes but are", "but are located", "are located across", "located across distal", "distal cpg", "cpg rich domains", "rich domains which", "domains which have", "which have partial", "have partial dna", "partial dna methylation", "methylation xia", "2019 . at", ". at the", "at the 8", "the 8 cell", "8 cell stage", "stage expression", "expression of kdm5b", "of kdm5b increases", "kdm5b increases and", "increases and the", "and the h3k4me3", "the h3k4me3 at", "h3k4me3 at the", "at the distal", "the distal domains", "distal domains is", "domains is lost", "is lost as", "lost as zygotic", "as zygotic genome", "genome activation occurs", "occurs suggesting", "suggesting a role", "a role for", "role for kdm5b", "for kdm5b in", "kdm5b in loss", "in loss of", "loss of h3k4me3", "h3k4me3 xia", "chromatin in the zygotic", "in the zygotic pronuclei", "the zygotic pronuclei transitions", "zygotic pronuclei transitions to", "pronuclei transitions to a", "transitions to a more", "to a more open", "a more open and", "more open and accessible", "open and accessible conformation", "and accessible conformation by", "accessible conformation by dna", "conformation by dna demethylation", "by dna demethylation and", "dna demethylation and changes", "demethylation and changes to", "and changes to histone", "changes to histone modifications.", "to histone modifications. as", "histone modifications. as development", "modifications. as development proceeds", "as development proceeds through", "development proceeds through the", "proceeds through the cleavage", "through the cleavage stages", "the cleavage stages to", "cleavage stages to the", "stages to the blastocyst", "the blastocyst chromatin", "blastocyst chromatin continues", "chromatin continues to become", "continues to become more", "to become more accessible", "become more accessible until", "more accessible until dna", "accessible until dna methylation", "until dna methylation and", "dna methylation and a", "methylation and a more", "and a more restrictive", "a more restrictive chromatin", "more restrictive chromatin conformation", "restrictive chromatin conformation are", "chromatin conformation are re", "conformation are re established", "are re established after", "re established after implantation", "established after implantation of", "after implantation of the", "implantation of the embryo", "of the embryo in", "the embryo in the", "embryo in the uterus.
              in", "in the uterus.
              in the", "the uterus.
              in the oocyte", "the oocyte h3k9me2", "oocyte h3k9me2 produced", "h3k9me2 produced by ehmt2", "by ehmt2 g9a", "kmt1c and h3k9me3", "and h3k9me3 produced by", "h3k9me3 produced by setdb1", "by setdb1 kmt1e", "kmt1e are transmitted", "are transmitted to the", "transmitted to the female", "to the female pronucleus", "the female pronucleus of", "female pronucleus of the", "pronucleus of the zygote", "of the zygote and", "the zygote and protect", "zygote and protect maternal", "and protect maternal dna", "protect maternal dna from", "maternal dna from active", "dna from active demethylation", "active demethylation inferred", "demethylation inferred from", "inferred from mouse zygotes", "from mouse zygotes in", "mouse zygotes in zeng", "zygotes in zeng et", "in zeng et al.", "zeng et al. 2019", "al. 2019 reviewed", "2019 reviewed in", "reviewed in de macedo", "in de macedo et", "de macedo et al.", "macedo et al. 2021", "et al. 2021 .", "al. 2021 . dppa3", "2021 . dppa3 binds", ". dppa3 binds h3k9me2", "binds h3k9me2 preventing", "h3k9me2 preventing the", "preventing the 5 methylcytosine", "the 5 methylcytosine oxidase", "5 methylcytosine oxidase tet3", "methylcytosine oxidase tet3 from", "oxidase tet3 from being", "tet3 from being recruited", "from being recruited to", "being recruited to chromatin", "to chromatin inferred", "chromatin inferred from", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in nakamura", "homologs in nakamura et", "in nakamura et al.", "nakamura et al. 2007", "al. 2007 wossidlo", "2007 wossidlo et", "wossidlo et al. 2011", "al. 2011 nakamura", "2011 nakamura et", "nakamura et al. 2012", "et al. 2012 .", "al. 2012 . dppa3", "2012 . dppa3 also", ". dppa3 also displaces", "dppa3 also displaces uhrf1", "also displaces uhrf1 from", "displaces uhrf1 from chromatin", "from chromatin preventing", "chromatin preventing the", "preventing the maintenance dna", "the maintenance dna methylase", "maintenance dna methylase dnmt1", "dna methylase dnmt1 from", "methylase dnmt1 from being", "dnmt1 from being recruited", "recruited to chromatin and", "to chromatin and thus", "chromatin and thus allowing", "and thus allowing passive", "thus allowing passive dna", "allowing passive dna demethylation", "passive dna demethylation to", "dna demethylation to occur", "demethylation to occur in", "to occur in the", "occur in the female", "in the female genome", "female genome inferred", "genome inferred from", "mouse homologs in funaki", "homologs in funaki et", "in funaki et al.", "funaki et al. 2014", "al. 2014 li", "2014 li et", "li et al. 2018", "al. 2018 du", "2018 du et", "du et al. 2019", "al. 2019 mulholland", "2019 mulholland et", "mulholland et al. 2020", "et al. 2020 .
              in", "al. 2020 .
              in the", "2020 .
              in the male", ".
              in the male pronucleus", "the male pronucleus of", "male pronucleus of the", "the zygote aicda", "aid deaminates cytosine", "deaminates cytosine residues and", "cytosine residues and long", "residues and long patch", "and long patch repair", "long patch repair replaces", "patch repair replaces the", "repair replaces the mismatches", "replaces the mismatches and", "the mismatches and adjacent", "mismatches and adjacent 5", "and adjacent 5 methylcytidine", "adjacent 5 methylcytidine residues", "5 methylcytidine residues with", "methylcytidine residues with cytidine", "with cytidine santos", "cytidine santos et", "santos et al. 2013", "al. 2013 franchini", "2013 franchini et", "franchini et al. 2014", "et al. 2014 .", "al. 2014 . after", "2014 . after this", ". after this initial", "after this initial demethylation", "initial demethylation tet3", "demethylation tet3 is", "tet3 is recruited to", "is recruited to chromatin", "recruited to chromatin by", "to chromatin by mettl23", "chromatin by mettl23 and", "by mettl23 and stgp4", "and stgp4 gse", "gse inferred", "mouse homologs in hatanaka", "homologs in hatanaka et", "in hatanaka et al.", "hatanaka et al. 2017", "al. 2017 where", "2017 where it", "where it oxidizes remaining", "it oxidizes remaining 5", "oxidizes remaining 5 methylcytidine", "remaining 5 methylcytidine to", "5 methylcytidine to 5", "methylcytidine to 5 hydroxymethylcytidine", "5 hydroxymethylcytidine which", "hydroxymethylcytidine which is", "which is removed by", "is removed by base", "removed by base excision", "by base excision repair", "base excision repair and", "excision repair and replaced", "repair and replaced with", "and replaced with cytidine", "with cytidine inferred", "cytidine inferred from", "mouse homologs in gu", "homologs in gu et", "in gu et al.", "gu et al. 2011", "al. 2011 iqbal", "2011 iqbal et", "iqbal et al. 2011", "al. 2011 wossidlo", "2011 wossidlo et", "al. 2011 santos", "2011 santos et", "al. 2013 amouroux", "2013 amouroux et", "amouroux et al. 2016", "al. 2016 hatanaka", "2016 hatanaka et", "et al. 2017 .
              the", "al. 2017 .
              the repressive", "2017 .
              the repressive mark", ".
              the repressive mark h3k27me3", "repressive mark h3k27me3 decreases", "mark h3k27me3 decreases in", "h3k27me3 decreases in 2", "decreases in 2 cell", "in 2 cell embryos", "2 cell embryos near", "cell embryos near developmentally", "embryos near developmentally related", "near developmentally related genes", "related genes xia", "genes xia et", "xia et al. 2019", "et al. 2019 .", "al. 2019 . the", "2019 . the h3k27me3", ". the h3k27me3 demethylases", "the h3k27me3 demethylases kdm6b", "demethylases kdm6b inferred", "kdm6b inferred from", "inferred from bovine embryos", "from bovine embryos in", "bovine embryos in chung", "embryos in chung et", "in chung et al.", "chung et al. 2017", "al. 2017 canovas", "2017 canovas et", "canovas et al. 2012", "al. 2012 and", "2012 and kdm6a", "and kdm6a inferred", "kdm6a inferred from", "inferred from mouse embryos", "from mouse embryos in", "mouse embryos in bai", "embryos in bai et", "in bai et al.", "bai et al. 2019", "al. 2019 appear", "2019 appear to", "appear to play a", "to play a role", "play a role in", "a role in the", "role in the decrease", "in the decrease of", "the decrease of h3k27me3", "of h3k27me3 as", "h3k27me3 as downregulation", "as downregulation of them", "downregulation of them impairs", "of them impairs h3k27me3", "them impairs h3k27me3 loss", "h3k27me3 loss zygotic", "loss zygotic genome", "genome activation and", "activation and embryonic", "and embryonic development. embryonic", "embryonic development. embryonic development", "development. embryonic development also", "embryonic development also requires", "development also requires h3k36me3", "requires h3k36me3 a", "h3k36me3 a permissive", "a permissive mark located", "permissive mark located in", "mark located in transcribed", "located in transcribed gene", "in transcribed gene bodies", "transcribed gene bodies that", "gene bodies that is", "bodies that is produced", "that is produced in", "is produced in the", "produced in the oocyte", "in the oocyte by", "the oocyte by setd2", "by setd2 inferred", "setd2 inferred from", "mouse embryos in xu", "embryos in xu et", "in xu et al.", "xu et al. 2019", "et al. 2019 .
              in", "al. 2019 .
              in mouse", "2019 .
              in mouse oocytes", "mouse oocytes h3k4me3", "oocytes h3k4me3 occurs", "h3k4me3 occurs in unusually", "occurs in unusually broad", "in unusually broad regions", "unusually broad regions that", "broad regions that span", "regions that span genes", "that span genes dahl", "span genes dahl et", "genes dahl et al.", "dahl et al. 2016", "al. 2016 zhang", "2016 zhang et", "zhang et al. 2016", "et al. 2016 .", "al. 2016 . these", "2016 . these broad", ". these broad regions", "these broad regions persist", "broad regions persist in", "regions persist in the", "persist in the zygote", "in the zygote and", "the zygote and into", "zygote and into the", "and into the 2", "into the 2 cell", "the 2 cell stage.", "2 cell stage. in", "cell stage. in the", "stage. in the late", "in the late 2", "the late 2 cell", "late 2 cell stage", "2 cell stage the", "cell stage the more", "stage the more usual", "the more usual patterns", "more usual patterns of", "usual patterns of h3k4me3", "patterns of h3k4me3 are", "of h3k4me3 are established", "h3k4me3 are established as", "are established as sharp", "established as sharp peaks", "as sharp peaks of", "sharp peaks of h3k4me3", "peaks of h3k4me3 near", "of h3k4me3 near the", "h3k4me3 near the transcription", "near the transcription start", "the transcription start sites", "transcription start sites and", "start sites and stop", "sites and stop sites", "and stop sites of", "stop sites of genes.", "sites of genes. the", "of genes. the histone", "genes. the histone methyltransferase", "the histone methyltransferase kmt2b", "histone methyltransferase kmt2b is", "methyltransferase kmt2b is at", "kmt2b is at least", "is at least partly", "at least partly responsible", "least partly responsible for", "partly responsible for establishing", "responsible for establishing the", "for establishing the broad", "establishing the broad regions", "the broad regions of", "broad regions of h3k4me3", "regions of h3k4me3 in", "of h3k4me3 in the", "h3k4me3 in the oocyte", "in the oocyte and", "the oocyte and the", "oocyte and the histone", "and the histone demethylases", "the histone demethylases kdm5b", "histone demethylases kdm5b and", "demethylases kdm5b and kdm5a", "kdm5b and kdm5a remove", "and kdm5a remove the", "kdm5a remove the broad", "remove the broad h3k4me3", "the broad h3k4me3 in", "broad h3k4me3 in the", "h3k4me3 in the late", "2 cell stage embryo", "stage embryo inferred", "embryo inferred from", "mouse homologs in dahl", "homologs in dahl et", "in dahl et al.", "al. 2016 reviewed", "2016 reviewed in", "reviewed in eckerseley maslin", "in eckerseley maslin et", "eckerseley maslin et al.", "maslin et al. 2018", "et al. 2018 .
              in", "al. 2018 .
              in human", "2018 .
              in human oocytes", ".
              in human oocytes and", "human oocytes and zygotes", "and zygotes however", "however broad regions", "regions of h3k4me3 are", "of h3k4me3 are not", "h3k4me3 are not observed", "are not observed across", "not observed across genes", "observed across genes but", "across genes but are", "genes but are located", "but are located across", "are located across distal", "across distal cpg", "distal cpg rich", "cpg rich domains which", "rich domains which have", "domains which have partial", "which have partial dna", "have partial dna methylation", "dna methylation xia", "methylation xia et", "al. 2019 . at", "2019 . at the", ". at the 8", "at the 8 cell", "the 8 cell stage", "cell stage expression", "stage expression of", "expression of kdm5b increases", "of kdm5b increases and", "kdm5b increases and the", "increases and the h3k4me3", "and the h3k4me3 at", "the h3k4me3 at the", "h3k4me3 at the distal", "at the distal domains", "the distal domains is", "distal domains is lost", "domains is lost as", "is lost as zygotic", "lost as zygotic genome", "as zygotic genome activation", "zygotic genome activation occurs", "activation occurs suggesting", "occurs suggesting a", "suggesting a role for", "a role for kdm5b", "role for kdm5b in", "for kdm5b in loss", "kdm5b in loss of", "in loss of h3k4me3", "of h3k4me3 xia", "h3k4me3 xia et", "chromatin in the zygotic pronuclei", "in the zygotic pronuclei transitions", "the zygotic pronuclei transitions to", "zygotic pronuclei transitions to a", "pronuclei transitions to a more", "transitions to a more open", "to a more open and", "a more open and accessible", "more open and accessible conformation", "open and accessible conformation by", "and accessible conformation by dna", "accessible conformation by dna demethylation", "conformation by dna demethylation and", "by dna demethylation and changes", "dna demethylation and changes to", "demethylation and changes to histone", "and changes to histone modifications.", "changes to histone modifications. as", "to histone modifications. as development", "histone modifications. as development proceeds", "modifications. as development proceeds through", "as development proceeds through the", "development proceeds through the cleavage", "proceeds through the cleavage stages", "through the cleavage stages to", "the cleavage stages to the", "cleavage stages to the blastocyst", "to the blastocyst chromatin", "the blastocyst chromatin continues", "blastocyst chromatin continues to", "chromatin continues to become more", "continues to become more accessible", "to become more accessible until", "become more accessible until dna", "more accessible until dna methylation", "accessible until dna methylation and", "until dna methylation and a", "dna methylation and a more", "methylation and a more restrictive", "and a more restrictive chromatin", "a more restrictive chromatin conformation", "more restrictive chromatin conformation are", "restrictive chromatin conformation are re", "chromatin conformation are re established", "conformation are re established after", "are re established after implantation", "re established after implantation of", "established after implantation of the", "after implantation of the embryo", "implantation of the embryo in", "of the embryo in the", "the embryo in the uterus.
              in", "embryo in the uterus.
              in the", "in the uterus.
              in the oocyte", "uterus.
              in the oocyte h3k9me2", "the oocyte h3k9me2 produced", "oocyte h3k9me2 produced by", "produced by ehmt2 g9a", "ehmt2 g9a kmt1c", "g9a kmt1c and", "kmt1c and h3k9me3 produced", "and h3k9me3 produced by setdb1", "produced by setdb1 kmt1e", "setdb1 kmt1e are", "kmt1e are transmitted to", "are transmitted to the female", "transmitted to the female pronucleus", "to the female pronucleus of", "the female pronucleus of the", "female pronucleus of the zygote", "pronucleus of the zygote and", "of the zygote and protect", "the zygote and protect maternal", "zygote and protect maternal dna", "and protect maternal dna from", "protect maternal dna from active", "maternal dna from active demethylation", "from active demethylation inferred", "active demethylation inferred from", "demethylation inferred from mouse", "inferred from mouse zygotes in", "from mouse zygotes in zeng", "mouse zygotes in zeng et", "zygotes in zeng et al.", "in zeng et al. 2019", "et al. 2019 reviewed", "al. 2019 reviewed in", "2019 reviewed in de", "reviewed in de macedo et", "in de macedo et al.", "de macedo et al. 2021", "macedo et al. 2021 .", "et al. 2021 . dppa3", "al. 2021 . dppa3 binds", "2021 . dppa3 binds h3k9me2", "dppa3 binds h3k9me2 preventing", "binds h3k9me2 preventing the", "h3k9me2 preventing the 5", "preventing the 5 methylcytosine oxidase", "the 5 methylcytosine oxidase tet3", "5 methylcytosine oxidase tet3 from", "methylcytosine oxidase tet3 from being", "oxidase tet3 from being recruited", "tet3 from being recruited to", "from being recruited to chromatin", "recruited to chromatin inferred", "to chromatin inferred from", "chromatin inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in nakamura", "mouse homologs in nakamura et", "homologs in nakamura et al.", "in nakamura et al. 2007", "et al. 2007 wossidlo", "al. 2007 wossidlo et", "2007 wossidlo et al.", "et al. 2011 nakamura", "al. 2011 nakamura et", "2011 nakamura et al.", "nakamura et al. 2012 .", "et al. 2012 . dppa3", "al. 2012 . dppa3 also", "2012 . dppa3 also displaces", ". dppa3 also displaces uhrf1", "dppa3 also displaces uhrf1 from", "also displaces uhrf1 from chromatin", "uhrf1 from chromatin preventing", "from chromatin preventing the", "chromatin preventing the maintenance", "preventing the maintenance dna methylase", "the maintenance dna methylase dnmt1", "maintenance dna methylase dnmt1 from", "dna methylase dnmt1 from being", "methylase dnmt1 from being recruited", "dnmt1 from being recruited to", "being recruited to chromatin and", "recruited to chromatin and thus", "to chromatin and thus allowing", "chromatin and thus allowing passive", "and thus allowing passive dna", "thus allowing passive dna demethylation", "allowing passive dna demethylation to", "passive dna demethylation to occur", "dna demethylation to occur in", "demethylation to occur in the", "to occur in the female", "occur in the female genome", "the female genome inferred", "female genome inferred from", "genome inferred from mouse", "from mouse homologs in funaki", "mouse homologs in funaki et", "homologs in funaki et al.", "in funaki et al. 2014", "et al. 2014 li", "al. 2014 li et", "2014 li et al.", "et al. 2018 du", "al. 2018 du et", "2018 du et al.", "et al. 2019 mulholland", "al. 2019 mulholland et", "2019 mulholland et al.", "mulholland et al. 2020 .
              in", "et al. 2020 .
              in the", "al. 2020 .
              in the male", "2020 .
              in the male pronucleus", ".
              in the male pronucleus of", "the male pronucleus of the", "male pronucleus of the zygote", "of the zygote aicda", "zygote aicda aid", "aicda aid deaminates", "aid deaminates cytosine residues", "deaminates cytosine residues and long", "cytosine residues and long patch", "residues and long patch repair", "and long patch repair replaces", "long patch repair replaces the", "patch repair replaces the mismatches", "repair replaces the mismatches and", "replaces the mismatches and adjacent", "the mismatches and adjacent 5", "mismatches and adjacent 5 methylcytidine", "and adjacent 5 methylcytidine residues", "adjacent 5 methylcytidine residues with", "5 methylcytidine residues with cytidine", "residues with cytidine santos", "with cytidine santos et", "cytidine santos et al.", "et al. 2013 franchini", "al. 2013 franchini et", "2013 franchini et al.", "franchini et al. 2014 .", "et al. 2014 . after", "al. 2014 . after this", "2014 . after this initial", ". after this initial demethylation", "this initial demethylation tet3", "initial demethylation tet3 is", "demethylation tet3 is recruited", "tet3 is recruited to chromatin", "is recruited to chromatin by", "recruited to chromatin by mettl23", "to chromatin by mettl23 and", "chromatin by mettl23 and stgp4", "mettl23 and stgp4 gse", "gse inferred from", "from mouse homologs in hatanaka", "mouse homologs in hatanaka et", "homologs in hatanaka et al.", "in hatanaka et al. 2017", "et al. 2017 where", "al. 2017 where it", "2017 where it oxidizes", "where it oxidizes remaining 5", "it oxidizes remaining 5 methylcytidine", "oxidizes remaining 5 methylcytidine to", "remaining 5 methylcytidine to 5", "5 methylcytidine to 5 hydroxymethylcytidine", "to 5 hydroxymethylcytidine which", "5 hydroxymethylcytidine which is", "hydroxymethylcytidine which is removed", "which is removed by base", "is removed by base excision", "removed by base excision repair", "by base excision repair and", "base excision repair and replaced", "excision repair and replaced with", "repair and replaced with cytidine", "replaced with cytidine inferred", "with cytidine inferred from", "cytidine inferred from mouse", "from mouse homologs in gu", "mouse homologs in gu et", "homologs in gu et al.", "in gu et al. 2011", "et al. 2011 iqbal", "al. 2011 iqbal et", "2011 iqbal et al.", "et al. 2011 wossidlo", "al. 2011 wossidlo et", "2011 wossidlo et al.", "et al. 2011 santos", "al. 2011 santos et", "2011 santos et al.", "et al. 2013 amouroux", "al. 2013 amouroux et", "2013 amouroux et al.", "et al. 2016 hatanaka", "al. 2016 hatanaka et", "2016 hatanaka et al.", "hatanaka et al. 2017 .
              the", "et al. 2017 .
              the repressive", "al. 2017 .
              the repressive mark", "2017 .
              the repressive mark h3k27me3", ".
              the repressive mark h3k27me3 decreases", "repressive mark h3k27me3 decreases in", "mark h3k27me3 decreases in 2", "h3k27me3 decreases in 2 cell", "decreases in 2 cell embryos", "in 2 cell embryos near", "2 cell embryos near developmentally", "cell embryos near developmentally related", "embryos near developmentally related genes", "developmentally related genes xia", "related genes xia et", "genes xia et al.", "xia et al. 2019 .", "et al. 2019 . the", "al. 2019 . the h3k27me3", "2019 . the h3k27me3 demethylases", ". the h3k27me3 demethylases kdm6b", "h3k27me3 demethylases kdm6b inferred", "demethylases kdm6b inferred from", "kdm6b inferred from bovine", "inferred from bovine embryos in", "from bovine embryos in chung", "bovine embryos in chung et", "embryos in chung et al.", "in chung et al. 2017", "et al. 2017 canovas", "al. 2017 canovas et", "2017 canovas et al.", "et al. 2012 and", "al. 2012 and kdm6a", "and kdm6a inferred from", "kdm6a inferred from mouse", "inferred from mouse embryos in", "from mouse embryos in bai", "mouse embryos in bai et", "embryos in bai et al.", "in bai et al. 2019", "et al. 2019 appear", "al. 2019 appear to", "2019 appear to play", "appear to play a role", "to play a role in", "play a role in the", "a role in the decrease", "role in the decrease of", "in the decrease of h3k27me3", "decrease of h3k27me3 as", "of h3k27me3 as downregulation", "h3k27me3 as downregulation of", "as downregulation of them impairs", "downregulation of them impairs h3k27me3", "of them impairs h3k27me3 loss", "impairs h3k27me3 loss zygotic", "h3k27me3 loss zygotic genome", "loss zygotic genome activation", "zygotic genome activation and", "genome activation and embryonic", "activation and embryonic development.", "and embryonic development. embryonic development", "embryonic development. embryonic development also", "development. embryonic development also requires", "embryonic development also requires h3k36me3", "also requires h3k36me3 a", "requires h3k36me3 a permissive", "h3k36me3 a permissive mark", "a permissive mark located in", "permissive mark located in transcribed", "mark located in transcribed gene", "located in transcribed gene bodies", "in transcribed gene bodies that", "transcribed gene bodies that is", "gene bodies that is produced", "bodies that is produced in", "that is produced in the", "is produced in the oocyte", "produced in the oocyte by", "in the oocyte by setd2", "oocyte by setd2 inferred", "by setd2 inferred from", "setd2 inferred from mouse", "from mouse embryos in xu", "mouse embryos in xu et", "embryos in xu et al.", "in xu et al. 2019", "xu et al. 2019 .
              in", "et al. 2019 .
              in mouse", "al. 2019 .
              in mouse oocytes", ".
              in mouse oocytes h3k4me3", "mouse oocytes h3k4me3 occurs", "oocytes h3k4me3 occurs in", "h3k4me3 occurs in unusually broad", "occurs in unusually broad regions", "in unusually broad regions that", "unusually broad regions that span", "broad regions that span genes", "regions that span genes dahl", "that span genes dahl et", "span genes dahl et al.", "genes dahl et al. 2016", "et al. 2016 zhang", "al. 2016 zhang et", "2016 zhang et al.", "zhang et al. 2016 .", "et al. 2016 . these", "al. 2016 . these broad", "2016 . these broad regions", ". these broad regions persist", "these broad regions persist in", "broad regions persist in the", "regions persist in the zygote", "persist in the zygote and", "in the zygote and into", "the zygote and into the", "zygote and into the 2", "and into the 2 cell", "into the 2 cell stage.", "the 2 cell stage. in", "2 cell stage. in the", "cell stage. in the late", "stage. in the late 2", "in the late 2 cell", "the late 2 cell stage", "late 2 cell stage the", "2 cell stage the more", "cell stage the more usual", "stage the more usual patterns", "the more usual patterns of", "more usual patterns of h3k4me3", "usual patterns of h3k4me3 are", "patterns of h3k4me3 are established", "of h3k4me3 are established as", "h3k4me3 are established as sharp", "are established as sharp peaks", "established as sharp peaks of", "as sharp peaks of h3k4me3", "sharp peaks of h3k4me3 near", "peaks of h3k4me3 near the", "of h3k4me3 near the transcription", "h3k4me3 near the transcription start", "near the transcription start sites", "the transcription start sites and", "transcription start sites and stop", "start sites and stop sites", "sites and stop sites of", "and stop sites of genes.", "stop sites of genes. the", "sites of genes. the histone", "of genes. the histone methyltransferase", "genes. the histone methyltransferase kmt2b", "the histone methyltransferase kmt2b is", "histone methyltransferase kmt2b is at", "methyltransferase kmt2b is at least", "kmt2b is at least partly", "is at least partly responsible", "at least partly responsible for", "least partly responsible for establishing", "partly responsible for establishing the", "responsible for establishing the broad", "for establishing the broad regions", "establishing the broad regions of", "the broad regions of h3k4me3", "broad regions of h3k4me3 in", "regions of h3k4me3 in the", "of h3k4me3 in the oocyte", "h3k4me3 in the oocyte and", "in the oocyte and the", "the oocyte and the histone", "oocyte and the histone demethylases", "and the histone demethylases kdm5b", "the histone demethylases kdm5b and", "histone demethylases kdm5b and kdm5a", "demethylases kdm5b and kdm5a remove", "kdm5b and kdm5a remove the", "and kdm5a remove the broad", "kdm5a remove the broad h3k4me3", "remove the broad h3k4me3 in", "the broad h3k4me3 in the", "broad h3k4me3 in the late", "h3k4me3 in the late 2", "late 2 cell stage embryo", "cell stage embryo inferred", "stage embryo inferred from", "embryo inferred from mouse", "from mouse homologs in dahl", "mouse homologs in dahl et", "homologs in dahl et al.", "in dahl et al. 2016", "et al. 2016 reviewed", "al. 2016 reviewed in", "2016 reviewed in eckerseley", "reviewed in eckerseley maslin et", "in eckerseley maslin et al.", "eckerseley maslin et al. 2018", "maslin et al. 2018 .
              in", "et al. 2018 .
              in human", "al. 2018 .
              in human oocytes", "2018 .
              in human oocytes and", ".
              in human oocytes and zygotes", "oocytes and zygotes however", "zygotes however broad", "however broad regions of", "broad regions of h3k4me3 are", "regions of h3k4me3 are not", "of h3k4me3 are not observed", "h3k4me3 are not observed across", "are not observed across genes", "not observed across genes but", "observed across genes but are", "across genes but are located", "genes but are located across", "but are located across distal", "located across distal cpg", "across distal cpg rich", "distal cpg rich domains", "cpg rich domains which have", "rich domains which have partial", "domains which have partial dna", "which have partial dna methylation", "partial dna methylation xia", "dna methylation xia et", "methylation xia et al.", "et al. 2019 . at", "al. 2019 . at the", "2019 . at the 8", ". at the 8 cell", "at the 8 cell stage", "8 cell stage expression", "cell stage expression of", "stage expression of kdm5b", "expression of kdm5b increases and", "of kdm5b increases and the", "kdm5b increases and the h3k4me3", "increases and the h3k4me3 at", "and the h3k4me3 at the", "the h3k4me3 at the distal", "h3k4me3 at the distal domains", "at the distal domains is", "the distal domains is lost", "distal domains is lost as", "domains is lost as zygotic", "is lost as zygotic genome", "lost as zygotic genome activation", "as zygotic genome activation occurs", "genome activation occurs suggesting", "activation occurs suggesting a", "occurs suggesting a role", "suggesting a role for kdm5b", "a role for kdm5b in", "role for kdm5b in loss", "for kdm5b in loss of", "kdm5b in loss of h3k4me3", "loss of h3k4me3 xia", "of h3k4me3 xia et", "h3k4me3 xia et al." ] }, { "record_id": "GLY_000594_1_2122", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9833110", "r hsa", "hsa 9833110", "r hsa 9833110" ] }, { "record_id": "GLY_000594_1_2122", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "rsv host", "host interactions", "rsv host interactions", "airway epithelial", "epithelial cells", "cells are", "are the", "the primary", "primary target", "target for", "for human", "human respiratory", "respiratory syncytial", "syncytial virus", "and other", "other inhaled", "inhaled pathogens", "zhang et", "et al.", "2002 .", ". in", "in response", "response to", "to rsv", "rsv infection", "cells initiate", "initiate both", "both inflammatory", "inflammatory responses", "responses and", "and antiviral", "antiviral immune", "immune responses", "responses to", "to effectively", "effectively eliminate", "eliminate the", "the virus", "reviewed by", "by espinoza", "bueno et", "lay et", "hu et", "ouyang et", "2022 .", ". pattern", "pattern recognition", "recognition receptors", "including toll", "toll like", "like receptors", "and retinoic", "retinoic acid", "acid inducible", "inducible gene", "gene i", "i like", "detect viral", "viral components", "components such", "such as", "as rsv", "rsv genomic", "genomic rna", "rna and", "and trigger", "trigger the", "the production", "production of", "of pro", "pro inflammatory", "inflammatory cytokines", "and type", "type i", "i interferons", "liu et", "al. 2007", "espinoza et", ". additionally", "cells recruit", "recruit other", "other innate", "innate immune", "immune cells", "cells including", "including polymorphonuclear", "polymorphonuclear leukocytes", "and natural", "natural killer", "killer cells", "cells to", "to establish", "establish an", "an antiviral", "antiviral environment", "environment and", "and facilitate", "facilitate the", "the resolution", "resolution of", "of inflammation", "inflammation within", "within the", "the lungs", "miura 2019", "2019 .", ". the", "the impact", "impact of", "of rsv", "infection on", "on the", "the host", "host cell", "cell transcriptome", "transcriptome and", "and proteome", "proteome is", "is reviewed", "by hu", "2020. the", "the adaptive", "adaptive immune", "immune response", "response controls", "controls rsv", "infection by", "by secreting", "secreting antibodies", "jones et", "fong et", "or by", "by cytotoxic", "cytotoxic t", "t lymphocytes", "that recognize", "recognize and", "and eliminate", "eliminate rsv", "rsv infected", "infected cells", "lukens et", "de et", "2023 .", ". rsv", "rsv evolved", "evolved strategies", "strategies to", "to evade", "evade or", "or subvert", "subvert these", "these host", "host responses", "allowing an", "an infection", "infection to", "to be", "be established", "established and", "and persist", "persist within", "bohmwald et", "brasier 2020", "stephens &", "& varga", "varga 2020", "van royen", "royen et", ". for", "for example", "the ns1", "ns1 and", "and ns2", "ns2 proteins", "proteins target", "target the", "the signaling", "signaling molecules", "molecules involved", "involved in", "in the", "the innate", "response suppressing", "suppressing prr", "prr induced", "induced ifn", "ifn production", "production and", "and ifn", "ifn mediated", "mediated signaling", "signaling pathways", "by sedeyn", "sedeyn et", "thornhill &", "& verhoeven", "2020 .", ". viral", "viral sh", "sh has", "has been", "been implicated", "implicated in", "in inhibiting", "inhibiting apoptotic", "apoptotic pathway", "a type", "type of", "of non", "non inflammatory", "inflammatory cell", "cell death", "death that", "that limits", "limits viral", "viral propagation", "li et", "2015 .", ". at", "at the", "the same", "same time", "triantafilou et", "have reported", "reported that", "that viral", "sh promotes", "promotes an", "an inflammatory", "inflammatory necrotic", "necrotic cell", "death to", "to release", "release the", "the cell", "cell content.", "content. further", "the binding", "binding of", "rsv g", "g protein", "protein to", "to leukocytes", "leukocytes involves", "involves the", "host cx3c", "cx3c chemokine", "chemokine receptor", "receptor 1", "and results", "results in", "in blocking", "blocking signaling", "signaling and", "and trafficking", "trafficking of", "of cx3cr1", "cx3cr1 expressing", "expressing th1", "th1 immune", "to the", "facilitating rsv", "harcourt et", "2006 .", "the hrsv", "hrsv ns2", "ns2 protein", "protein induces", "induces cell", "cell shedding", "shedding into", "into large", "large airways", "airways causing", "causing an", "an acute", "acute airway", "airway obstruction", "obstruction in", "in an", "an animal", "animal model", "model of", "infection through", "through an", "an unknown", "unknown mechanism", "liesman et", "2014 .", ".

              several", "

              several host", "host factors", "factors contribute", "contribute to", "the pathogenesis", "pathogenesis of", "infection and", "and its", "its long", "long term", "term effects", "including age", "underlying respiratory", "respiratory conditions", "conditions such", "as chronic", "chronic lung", "lung disease", "disease including", "including cystic", "cystic fibrosis", "deficiencies in", "in specific", "specific immune", "immune components", "components or", "or dysregulated", "dysregulated immune", "by carvajal", "carvajal et", "in some", "some cases", "an exaggerated", "exaggerated immune", "infection can", "can affect", "affect the", "the host's", "host's ability", "ability to", "to control", "control viral", "viral infection", "infection leading", "leading to", "to immunopathology.", "immunopathology. for", "elevated production", "of th2", "th2 type", "type cytokines", "il 4", "il 5", "5 and", "and il", "il 13", "infection leads", "leads to", "to airway", "airway hyperreactivity", "hyperreactivity and", "and increased", "increased risk", "risk of", "of developing", "developing asthma", "asthma after", "after hrsv", "hrsv infection", "vu et", "dong et", "by norlander", "norlander &", "& peebles", "peebles 2020", "manti &", "& piedimonte", "piedimonte 2022", "the outcome", "outcome of", "infection depends", "depends on", "on a", "a complex", "complex interplay", "interplay between", "between the", "the immune", "responses induced", "induced by", "by the", "host and", "and the", "the strategies", "strategies developed", "developed by", "by rsv", "rsv to", "to subvert", "these responses.

              this", "responses.

              this reactome", "reactome module", "module describes", "describes molecular", "molecular mechanisms", "mechanisms by", "by which", "which specific", "specific rsv", "rsv components", "components modulate", "modulate innate", "innate and", "and adaptive", "programmed cell", "and host", "host gene", "gene expression.", "airway epithelial cells", "epithelial cells are", "cells are the", "are the primary", "the primary target", "primary target for", "target for human", "for human respiratory", "human respiratory syncytial", "respiratory syncytial virus", "virus hrsv", "hrsv and", "and other inhaled", "other inhaled pathogens", "pathogens zhang", "zhang et al.", "al. 2002", "2002 . in", ". in response", "in response to", "response to rsv", "to rsv infection", "infection airway", "epithelial cells initiate", "cells initiate both", "initiate both inflammatory", "both inflammatory responses", "inflammatory responses and", "responses and antiviral", "and antiviral immune", "antiviral immune responses", "immune responses to", "responses to effectively", "to effectively eliminate", "effectively eliminate the", "eliminate the virus", "virus reviewed", "reviewed by espinoza", "espinoza bueno", "bueno et al.", "al. 2014", "2014 lay", "lay et al.", "al. 2016", "2016 hu", "hu et al.", "al. 2020", "2020 ouyang", "ouyang et al.", "al. 2022", "2022 . pattern", ". pattern recognition", "pattern recognition receptors", "receptors prrs", "including toll like", "toll like receptors", "receptors tlrs", "tlrs and", "and retinoic acid", "retinoic acid inducible", "acid inducible gene", "inducible gene i", "gene i like", "i like receptors", "receptors rlrs", "detect viral components", "viral components such", "components such as", "such as rsv", "as rsv genomic", "rsv genomic rna", "genomic rna and", "rna and trigger", "and trigger the", "trigger the production", "the production of", "production of pro", "of pro inflammatory", "pro inflammatory cytokines", "cytokines chemokines", "chemokines and", "and type i", "type i interferons", "interferons liu", "liu et al.", "et al. 2007", "2007 reviewed", "by espinoza et", "espinoza et al.", "2014 hu", "2022 . additionally", "additionally airway", "epithelial cells recruit", "cells recruit other", "recruit other innate", "other innate immune", "innate immune cells", "immune cells including", "cells including polymorphonuclear", "including polymorphonuclear leukocytes", "leukocytes pmns", "macrophages and", "and natural killer", "natural killer cells", "killer cells to", "cells to establish", "to establish an", "establish an antiviral", "an antiviral environment", "antiviral environment and", "environment and facilitate", "and facilitate the", "facilitate the resolution", "the resolution of", "resolution of inflammation", "of inflammation within", "inflammation within the", "within the lungs", "lungs miura", "miura 2019 .", "2019 . the", ". the impact", "the impact of", "impact of rsv", "of rsv infection", "rsv infection on", "infection on the", "on the host", "the host cell", "host cell transcriptome", "cell transcriptome and", "transcriptome and proteome", "and proteome is", "proteome is reviewed", "is reviewed by", "reviewed by hu", "by hu et", "al. 2020.", "2020. the adaptive", "the adaptive immune", "adaptive immune response", "immune response controls", "response controls rsv", "controls rsv infection", "rsv infection by", "infection by secreting", "by secreting antibodies", "antibodies jones", "jones et al.", "al. 2018", "2018 fong", "fong et al.", "al. 2023", "2023 or", "or by cytotoxic", "by cytotoxic t", "cytotoxic t lymphocytes", "lymphocytes ctls", "ctls that", "that recognize and", "recognize and eliminate", "and eliminate rsv", "eliminate rsv infected", "rsv infected cells", "cells lukens", "lukens et al.", "al. 2010", "2010 de", "de et al.", "2023 . rsv", ". rsv evolved", "rsv evolved strategies", "evolved strategies to", "strategies to evade", "to evade or", "evade or subvert", "or subvert these", "subvert these host", "these host responses", "responses allowing", "allowing an infection", "an infection to", "infection to be", "to be established", "be established and", "established and persist", "and persist within", "persist within the", "within the host", "host reviewed", "espinoza bohmwald", "bohmwald et al.", "2020 brasier", "2020 stephens", "stephens & varga", "& varga 2020", "2022 van", "van royen et", "royen et al.", "2022 . for", ". for example", "example the", "the ns1 and", "ns1 and ns2", "and ns2 proteins", "ns2 proteins target", "proteins target the", "target the signaling", "the signaling molecules", "signaling molecules involved", "molecules involved in", "involved in the", "in the innate", "the innate immune", "innate immune response", "immune response suppressing", "response suppressing prr", "suppressing prr induced", "prr induced ifn", "induced ifn production", "ifn production and", "production and ifn", "and ifn mediated", "ifn mediated signaling", "mediated signaling pathways", "pathways reviewed", "reviewed by sedeyn", "by sedeyn et", "sedeyn et al.", "al. 2019", "2019 thornhill", "thornhill & verhoeven", "verhoeven 2020", "2020 . viral", ". viral sh", "viral sh has", "sh has been", "has been implicated", "been implicated in", "implicated in inhibiting", "in inhibiting apoptotic", "inhibiting apoptotic pathway", "pathway a", "a type of", "type of non", "of non inflammatory", "non inflammatory cell", "inflammatory cell death", "cell death that", "death that limits", "that limits viral", "limits viral propagation", "propagation li", "li et al.", "al. 2015", "2015 . at", ". at the", "at the same", "the same time", "time triantafilou", "triantafilou et al.", "al. 2013", "2013 have", "have reported that", "reported that viral", "that viral sh", "viral sh promotes", "sh promotes an", "promotes an inflammatory", "an inflammatory necrotic", "inflammatory necrotic cell", "necrotic cell death", "cell death to", "death to release", "to release the", "release the cell", "the cell content.", "cell content. further", "further the", "the binding of", "binding of rsv", "of rsv g", "rsv g protein", "g protein to", "protein to leukocytes", "to leukocytes involves", "leukocytes involves the", "involves the host", "the host cx3c", "host cx3c chemokine", "cx3c chemokine receptor", "chemokine receptor 1", "1 cx3cr1", "cx3cr1 and", "and results in", "results in blocking", "in blocking signaling", "blocking signaling and", "signaling and trafficking", "and trafficking of", "trafficking of cx3cr1", "of cx3cr1 expressing", "cx3cr1 expressing th1", "expressing th1 immune", "th1 immune cells", "immune cells to", "cells to the", "to the lungs", "lungs facilitating", "facilitating rsv infection", "infection harcourt", "harcourt et al.", "al. 2006", "2006 . the", ". the hrsv", "the hrsv ns2", "hrsv ns2 protein", "ns2 protein induces", "protein induces cell", "induces cell shedding", "cell shedding into", "shedding into large", "into large airways", "large airways causing", "airways causing an", "causing an acute", "an acute airway", "acute airway obstruction", "airway obstruction in", "obstruction in an", "in an animal", "an animal model", "animal model of", "model of rsv", "rsv infection through", "infection through an", "through an unknown", "an unknown mechanism", "mechanism liesman", "liesman et al.", "2014 .

              several", ".

              several host", "

              several host factors", "host factors contribute", "factors contribute to", "contribute to the", "to the pathogenesis", "the pathogenesis of", "pathogenesis of rsv", "rsv infection and", "infection and its", "and its long", "its long term", "long term effects", "effects including", "age prematurity", "prematurity underlying", "underlying respiratory conditions", "respiratory conditions such", "conditions such as", "such as chronic", "as chronic lung", "chronic lung disease", "lung disease including", "disease including cystic", "including cystic fibrosis", "fibrosis deficiencies", "deficiencies in specific", "in specific immune", "specific immune components", "immune components or", "components or dysregulated", "or dysregulated immune", "dysregulated immune responses", "responses reviewed", "reviewed by carvajal", "by carvajal et", "carvajal et al.", "2019 . in", ". in some", "in some cases", "cases an", "an exaggerated immune", "exaggerated immune response", "immune response to", "rsv infection can", "infection can affect", "can affect the", "affect the host's", "the host's ability", "host's ability to", "ability to control", "to control viral", "control viral infection", "viral infection leading", "infection leading to", "leading to immunopathology.", "to immunopathology. for", "immunopathology. for example", "example elevated", "elevated production of", "production of th2", "of th2 type", "th2 type cytokines", "cytokines il", "4 il", "il 5 and", "5 and il", "and il 13", "13 in", "rsv infection leads", "infection leads to", "leads to airway", "to airway hyperreactivity", "airway hyperreactivity and", "hyperreactivity and increased", "and increased risk", "increased risk of", "risk of developing", "of developing asthma", "developing asthma after", "asthma after hrsv", "after hrsv infection", "infection vu", "vu et al.", "2019 dong", "dong et al.", "2023 reviewed", "reviewed by norlander", "by norlander &", "norlander & peebles", "& peebles 2020", "2020 manti", "manti & piedimonte", "& piedimonte 2022", "piedimonte 2022 .", "2022 . the", ". the outcome", "the outcome of", "outcome of rsv", "rsv infection depends", "infection depends on", "depends on a", "on a complex", "a complex interplay", "complex interplay between", "interplay between the", "between the immune", "the immune responses", "immune responses induced", "responses induced by", "induced by the", "by the host", "the host and", "host and the", "and the strategies", "the strategies developed", "strategies developed by", "developed by rsv", "by rsv to", "rsv to subvert", "to subvert these", "subvert these responses.

              this", "these responses.

              this reactome", "responses.

              this reactome module", "reactome module describes", "module describes molecular", "describes molecular mechanisms", "molecular mechanisms by", "mechanisms by which", "by which specific", "which specific rsv", "specific rsv components", "rsv components modulate", "components modulate innate", "modulate innate and", "innate and adaptive", "and adaptive immune", "adaptive immune responses", "responses programmed", "programmed cell death", "death and", "and host gene", "host gene expression.", "airway epithelial cells are", "epithelial cells are the", "cells are the primary", "are the primary target", "the primary target for", "primary target for human", "target for human respiratory", "for human respiratory syncytial", "human respiratory syncytial virus", "syncytial virus hrsv", "hrsv and other", "and other inhaled pathogens", "inhaled pathogens zhang", "pathogens zhang et", "et al. 2002", "al. 2002 .", "2002 . in response", ". in response to", "in response to rsv", "response to rsv infection", "rsv infection airway", "infection airway epithelial", "airway epithelial cells initiate", "epithelial cells initiate both", "cells initiate both inflammatory", "initiate both inflammatory responses", "both inflammatory responses and", "inflammatory responses and antiviral", "responses and antiviral immune", "and antiviral immune responses", "antiviral immune responses to", "immune responses to effectively", "responses to effectively eliminate", "to effectively eliminate the", "effectively eliminate the virus", "the virus reviewed", "virus reviewed by", "by espinoza bueno", "espinoza bueno et", "et al. 2014", "2014 lay et", "et al. 2016", "2016 hu et", "et al. 2020", "2020 ouyang et", "et al. 2022", "al. 2022 .", "2022 . pattern recognition", ". pattern recognition receptors", "recognition receptors prrs", "prrs including", "including toll like receptors", "like receptors tlrs", "tlrs and retinoic", "and retinoic acid inducible", "retinoic acid inducible gene", "acid inducible gene i", "inducible gene i like", "gene i like receptors", "like receptors rlrs", "rlrs detect", "detect viral components such", "viral components such as", "components such as rsv", "such as rsv genomic", "as rsv genomic rna", "rsv genomic rna and", "genomic rna and trigger", "rna and trigger the", "and trigger the production", "trigger the production of", "the production of pro", "production of pro inflammatory", "of pro inflammatory cytokines", "inflammatory cytokines chemokines", "chemokines and type", "and type i interferons", "i interferons liu", "interferons liu et", "liu et al. 2007", "al. 2007 reviewed", "2007 reviewed by", "reviewed by espinoza et", "by espinoza et al.", "2014 hu et", ". additionally airway", "additionally airway epithelial", "airway epithelial cells recruit", "epithelial cells recruit other", "cells recruit other innate", "recruit other innate immune", "other innate immune cells", "innate immune cells including", "immune cells including polymorphonuclear", "cells including polymorphonuclear leukocytes", "polymorphonuclear leukocytes pmns", "pmns macrophages", "macrophages and natural", "and natural killer cells", "natural killer cells to", "killer cells to establish", "cells to establish an", "to establish an antiviral", "establish an antiviral environment", "an antiviral environment and", "antiviral environment and facilitate", "environment and facilitate the", "and facilitate the resolution", "facilitate the resolution of", "the resolution of inflammation", "resolution of inflammation within", "of inflammation within the", "inflammation within the lungs", "the lungs miura", "lungs miura 2019", "miura 2019 . the", "2019 . the impact", ". the impact of", "the impact of rsv", "impact of rsv infection", "of rsv infection on", "rsv infection on the", "infection on the host", "on the host cell", "the host cell transcriptome", "host cell transcriptome and", "cell transcriptome and proteome", "transcriptome and proteome is", "and proteome is reviewed", "proteome is reviewed by", "is reviewed by hu", "reviewed by hu et", "by hu et al.", "et al. 2020.", "al. 2020. the", "2020. the adaptive immune", "the adaptive immune response", "adaptive immune response controls", "immune response controls rsv", "response controls rsv infection", "controls rsv infection by", "rsv infection by secreting", "infection by secreting antibodies", "secreting antibodies jones", "antibodies jones et", "et al. 2018", "2018 fong et", "et al. 2023", "2023 or by", "or by cytotoxic t", "by cytotoxic t lymphocytes", "t lymphocytes ctls", "ctls that recognize", "that recognize and eliminate", "recognize and eliminate rsv", "and eliminate rsv infected", "eliminate rsv infected cells", "infected cells lukens", "cells lukens et", "et al. 2010", "2010 de et", "al. 2023 .", "2023 . rsv evolved", ". rsv evolved strategies", "rsv evolved strategies to", "evolved strategies to evade", "strategies to evade or", "to evade or subvert", "evade or subvert these", "or subvert these host", "subvert these host responses", "host responses allowing", "responses allowing an", "allowing an infection to", "an infection to be", "infection to be established", "to be established and", "be established and persist", "established and persist within", "and persist within the", "persist within the host", "the host reviewed", "host reviewed by", "by espinoza bohmwald", "espinoza bohmwald et", "2020 brasier 2020", "brasier 2020 stephens", "2020 stephens &", "stephens & varga 2020", "varga 2020 ouyang", "2022 van royen", "van royen et al.", "2022 . for example", "for example the", "example the ns1", "the ns1 and ns2", "ns1 and ns2 proteins", "and ns2 proteins target", "ns2 proteins target the", "proteins target the signaling", "target the signaling molecules", "the signaling molecules involved", "signaling molecules involved in", "molecules involved in the", "involved in the innate", "in the innate immune", "the innate immune response", "innate immune response suppressing", "immune response suppressing prr", "response suppressing prr induced", "suppressing prr induced ifn", "prr induced ifn production", "induced ifn production and", "ifn production and ifn", "production and ifn mediated", "and ifn mediated signaling", "ifn mediated signaling pathways", "signaling pathways reviewed", "pathways reviewed by", "reviewed by sedeyn et", "by sedeyn et al.", "et al. 2019", "2019 thornhill &", "& verhoeven 2020", "verhoeven 2020 .", "2020 . viral sh", ". viral sh has", "viral sh has been", "sh has been implicated", "has been implicated in", "been implicated in inhibiting", "implicated in inhibiting apoptotic", "in inhibiting apoptotic pathway", "apoptotic pathway a", "pathway a type", "a type of non", "type of non inflammatory", "of non inflammatory cell", "non inflammatory cell death", "inflammatory cell death that", "cell death that limits", "death that limits viral", "that limits viral propagation", "viral propagation li", "propagation li et", "et al. 2015", "al. 2015 .", "2015 . at the", ". at the same", "at the same time", "same time triantafilou", "time triantafilou et", "et al. 2013", "2013 have reported", "have reported that viral", "reported that viral sh", "that viral sh promotes", "viral sh promotes an", "sh promotes an inflammatory", "promotes an inflammatory necrotic", "an inflammatory necrotic cell", "inflammatory necrotic cell death", "necrotic cell death to", "cell death to release", "death to release the", "to release the cell", "release the cell content.", "the cell content. further", "content. further the", "further the binding", "the binding of rsv", "binding of rsv g", "of rsv g protein", "rsv g protein to", "g protein to leukocytes", "protein to leukocytes involves", "to leukocytes involves the", "leukocytes involves the host", "involves the host cx3c", "the host cx3c chemokine", "host cx3c chemokine receptor", "cx3c chemokine receptor 1", "receptor 1 cx3cr1", "cx3cr1 and results", "and results in blocking", "results in blocking signaling", "in blocking signaling and", "blocking signaling and trafficking", "signaling and trafficking of", "and trafficking of cx3cr1", "trafficking of cx3cr1 expressing", "of cx3cr1 expressing th1", "cx3cr1 expressing th1 immune", "expressing th1 immune cells", "th1 immune cells to", "immune cells to the", "cells to the lungs", "the lungs facilitating", "lungs facilitating rsv", "rsv infection harcourt", "infection harcourt et", "et al. 2006", "al. 2006 .", "2006 . the hrsv", ". the hrsv ns2", "the hrsv ns2 protein", "hrsv ns2 protein induces", "ns2 protein induces cell", "protein induces cell shedding", "induces cell shedding into", "cell shedding into large", "shedding into large airways", "into large airways causing", "large airways causing an", "airways causing an acute", "causing an acute airway", "an acute airway obstruction", "acute airway obstruction in", "airway obstruction in an", "obstruction in an animal", "in an animal model", "an animal model of", "animal model of rsv", "model of rsv infection", "of rsv infection through", "rsv infection through an", "infection through an unknown", "through an unknown mechanism", "unknown mechanism liesman", "mechanism liesman et", "al. 2014 .", "2014 .

              several host", ".

              several host factors", "

              several host factors contribute", "host factors contribute to", "factors contribute to the", "contribute to the pathogenesis", "to the pathogenesis of", "the pathogenesis of rsv", "pathogenesis of rsv infection", "of rsv infection and", "rsv infection and its", "infection and its long", "and its long term", "its long term effects", "term effects including", "effects including age", "including age prematurity", "prematurity underlying respiratory", "underlying respiratory conditions such", "respiratory conditions such as", "conditions such as chronic", "such as chronic lung", "as chronic lung disease", "chronic lung disease including", "lung disease including cystic", "disease including cystic fibrosis", "cystic fibrosis deficiencies", "fibrosis deficiencies in", "deficiencies in specific immune", "in specific immune components", "specific immune components or", "immune components or dysregulated", "components or dysregulated immune", "or dysregulated immune responses", "immune responses reviewed", "responses reviewed by", "reviewed by carvajal et", "by carvajal et al.", "al. 2019 .", "2019 . in some", ". in some cases", "some cases an", "cases an exaggerated", "an exaggerated immune response", "exaggerated immune response to", "immune response to rsv", "to rsv infection can", "rsv infection can affect", "infection can affect the", "can affect the host's", "affect the host's ability", "the host's ability to", "host's ability to control", "ability to control viral", "to control viral infection", "control viral infection leading", "viral infection leading to", "infection leading to immunopathology.", "leading to immunopathology. for", "to immunopathology. for example", "for example elevated", "example elevated production", "elevated production of th2", "production of th2 type", "of th2 type cytokines", "type cytokines il", "cytokines il 4", "il 4 il", "4 il 5", "il 5 and il", "5 and il 13", "il 13 in", "13 in response", "to rsv infection leads", "rsv infection leads to", "infection leads to airway", "leads to airway hyperreactivity", "to airway hyperreactivity and", "airway hyperreactivity and increased", "hyperreactivity and increased risk", "and increased risk of", "increased risk of developing", "risk of developing asthma", "of developing asthma after", "developing asthma after hrsv", "asthma after hrsv infection", "hrsv infection vu", "infection vu et", "2019 dong et", "2023 reviewed by", "reviewed by norlander &", "by norlander & peebles", "norlander & peebles 2020", "peebles 2020 manti", "2020 manti &", "manti & piedimonte 2022", "& piedimonte 2022 .", "piedimonte 2022 . the", "2022 . the outcome", ". the outcome of", "the outcome of rsv", "outcome of rsv infection", "of rsv infection depends", "rsv infection depends on", "infection depends on a", "depends on a complex", "on a complex interplay", "a complex interplay between", "complex interplay between the", "interplay between the immune", "between the immune responses", "the immune responses induced", "immune responses induced by", "responses induced by the", "induced by the host", "by the host and", "the host and the", "host and the strategies", "and the strategies developed", "the strategies developed by", "strategies developed by rsv", "developed by rsv to", "by rsv to subvert", "rsv to subvert these", "to subvert these responses.

              this", "subvert these responses.

              this reactome", "these responses.

              this reactome module", "responses.

              this reactome module describes", "reactome module describes molecular", "module describes molecular mechanisms", "describes molecular mechanisms by", "molecular mechanisms by which", "mechanisms by which specific", "by which specific rsv", "which specific rsv components", "specific rsv components modulate", "rsv components modulate innate", "components modulate innate and", "modulate innate and adaptive", "innate and adaptive immune", "and adaptive immune responses", "immune responses programmed", "responses programmed cell", "cell death and", "death and host", "and host gene expression.", "airway epithelial cells are the", "epithelial cells are the primary", "cells are the primary target", "are the primary target for", "the primary target for human", "primary target for human respiratory", "target for human respiratory syncytial", "for human respiratory syncytial virus", "respiratory syncytial virus hrsv", "virus hrsv and", "hrsv and other inhaled", "other inhaled pathogens zhang", "inhaled pathogens zhang et", "pathogens zhang et al.", "zhang et al. 2002", "et al. 2002 .", "al. 2002 . in", "2002 . in response to", ". in response to rsv", "in response to rsv infection", "to rsv infection airway", "rsv infection airway epithelial", "infection airway epithelial cells", "airway epithelial cells initiate both", "epithelial cells initiate both inflammatory", "cells initiate both inflammatory responses", "initiate both inflammatory responses and", "both inflammatory responses and antiviral", "inflammatory responses and antiviral immune", "responses and antiviral immune responses", "and antiviral immune responses to", "antiviral immune responses to effectively", "immune responses to effectively eliminate", "responses to effectively eliminate the", "to effectively eliminate the virus", "eliminate the virus reviewed", "the virus reviewed by", "virus reviewed by espinoza", "reviewed by espinoza bueno", "by espinoza bueno et", "espinoza bueno et al.", "bueno et al. 2014", "al. 2014 lay", "2014 lay et al.", "lay et al. 2016", "al. 2016 hu", "2016 hu et al.", "hu et al. 2020", "al. 2020 ouyang", "2020 ouyang et al.", "ouyang et al. 2022", "et al. 2022 .", "al. 2022 . pattern", "2022 . pattern recognition receptors", "pattern recognition receptors prrs", "prrs including toll", "toll like receptors tlrs", "receptors tlrs and", "tlrs and retinoic acid", "and retinoic acid inducible gene", "retinoic acid inducible gene i", "acid inducible gene i like", "inducible gene i like receptors", "i like receptors rlrs", "rlrs detect viral", "detect viral components such as", "viral components such as rsv", "components such as rsv genomic", "such as rsv genomic rna", "as rsv genomic rna and", "rsv genomic rna and trigger", "genomic rna and trigger the", "rna and trigger the production", "and trigger the production of", "trigger the production of pro", "the production of pro inflammatory", "production of pro inflammatory cytokines", "pro inflammatory cytokines chemokines", "cytokines chemokines and", "chemokines and type i", "type i interferons liu", "i interferons liu et", "interferons liu et al.", "et al. 2007 reviewed", "al. 2007 reviewed by", "2007 reviewed by espinoza", "reviewed by espinoza et al.", "espinoza et al. 2014", "al. 2014 hu", "2014 hu et al.", "al. 2022 . additionally", "2022 . additionally airway", ". additionally airway epithelial", "additionally airway epithelial cells", "airway epithelial cells recruit other", "epithelial cells recruit other innate", "cells recruit other innate immune", "recruit other innate immune cells", "other innate immune cells including", "innate immune cells including polymorphonuclear", "immune cells including polymorphonuclear leukocytes", "including polymorphonuclear leukocytes pmns", "macrophages and natural killer", "and natural killer cells to", "natural killer cells to establish", "killer cells to establish an", "cells to establish an antiviral", "to establish an antiviral environment", "establish an antiviral environment and", "an antiviral environment and facilitate", "antiviral environment and facilitate the", "environment and facilitate the resolution", "and facilitate the resolution of", "facilitate the resolution of inflammation", "the resolution of inflammation within", "resolution of inflammation within the", "of inflammation within the lungs", "within the lungs miura", "the lungs miura 2019", "lungs miura 2019 .", "miura 2019 . the impact", "2019 . the impact of", ". the impact of rsv", "the impact of rsv infection", "impact of rsv infection on", "of rsv infection on the", "rsv infection on the host", "infection on the host cell", "on the host cell transcriptome", "the host cell transcriptome and", "host cell transcriptome and proteome", "cell transcriptome and proteome is", "transcriptome and proteome is reviewed", "and proteome is reviewed by", "proteome is reviewed by hu", "is reviewed by hu et", "reviewed by hu et al.", "hu et al. 2020.", "et al. 2020. the", "al. 2020. the adaptive", "2020. the adaptive immune response", "the adaptive immune response controls", "adaptive immune response controls rsv", "immune response controls rsv infection", "response controls rsv infection by", "controls rsv infection by secreting", "rsv infection by secreting antibodies", "by secreting antibodies jones", "secreting antibodies jones et", "antibodies jones et al.", "jones et al. 2018", "al. 2018 fong", "2018 fong et al.", "fong et al. 2023", "al. 2023 or", "2023 or by cytotoxic", "or by cytotoxic t lymphocytes", "cytotoxic t lymphocytes ctls", "lymphocytes ctls that", "ctls that recognize and", "that recognize and eliminate rsv", "recognize and eliminate rsv infected", "and eliminate rsv infected cells", "rsv infected cells lukens", "infected cells lukens et", "cells lukens et al.", "lukens et al. 2010", "al. 2010 de", "2010 de et al.", "de et al. 2023", "et al. 2023 .", "al. 2023 . rsv", "2023 . rsv evolved strategies", ". rsv evolved strategies to", "rsv evolved strategies to evade", "evolved strategies to evade or", "strategies to evade or subvert", "to evade or subvert these", "evade or subvert these host", "or subvert these host responses", "these host responses allowing", "host responses allowing an", "responses allowing an infection", "allowing an infection to be", "an infection to be established", "infection to be established and", "to be established and persist", "be established and persist within", "established and persist within the", "and persist within the host", "within the host reviewed", "the host reviewed by", "host reviewed by espinoza", "reviewed by espinoza bohmwald", "by espinoza bohmwald et", "espinoza bohmwald et al.", "bohmwald et al. 2014", "al. 2020 brasier", "brasier 2020 stephens &", "2020 stephens & varga", "& varga 2020 ouyang", "varga 2020 ouyang et", "al. 2022 van", "2022 van royen et", "royen et al. 2022", "al. 2022 . for", ". for example the", "for example the ns1", "example the ns1 and", "the ns1 and ns2 proteins", "ns1 and ns2 proteins target", "and ns2 proteins target the", "ns2 proteins target the signaling", "proteins target the signaling molecules", "target the signaling molecules involved", "the signaling molecules involved in", "signaling molecules involved in the", "molecules involved in the innate", "involved in the innate immune", "in the innate immune response", "the innate immune response suppressing", "innate immune response suppressing prr", "immune response suppressing prr induced", "response suppressing prr induced ifn", "suppressing prr induced ifn production", "prr induced ifn production and", "induced ifn production and ifn", "ifn production and ifn mediated", "production and ifn mediated signaling", "and ifn mediated signaling pathways", "mediated signaling pathways reviewed", "signaling pathways reviewed by", "pathways reviewed by sedeyn", "reviewed by sedeyn et al.", "sedeyn et al. 2019", "al. 2019 thornhill", "2019 thornhill & verhoeven", "thornhill & verhoeven 2020", "& verhoeven 2020 .", "verhoeven 2020 . viral", "2020 . viral sh has", ". viral sh has been", "viral sh has been implicated", "sh has been implicated in", "has been implicated in inhibiting", "been implicated in inhibiting apoptotic", "implicated in inhibiting apoptotic pathway", "inhibiting apoptotic pathway a", "apoptotic pathway a type", "pathway a type of", "a type of non inflammatory", "type of non inflammatory cell", "of non inflammatory cell death", "non inflammatory cell death that", "inflammatory cell death that limits", "cell death that limits viral", "death that limits viral propagation", "limits viral propagation li", "viral propagation li et", "propagation li et al.", "li et al. 2015", "et al. 2015 .", "al. 2015 . at", "2015 . at the same", ". at the same time", "the same time triantafilou", "same time triantafilou et", "time triantafilou et al.", "triantafilou et al. 2013", "al. 2013 have", "2013 have reported that", "have reported that viral sh", "reported that viral sh promotes", "that viral sh promotes an", "viral sh promotes an inflammatory", "sh promotes an inflammatory necrotic", "promotes an inflammatory necrotic cell", "an inflammatory necrotic cell death", "inflammatory necrotic cell death to", "necrotic cell death to release", "cell death to release the", "death to release the cell", "to release the cell content.", "release the cell content. further", "cell content. further the", "content. further the binding", "further the binding of", "the binding of rsv g", "binding of rsv g protein", "of rsv g protein to", "rsv g protein to leukocytes", "g protein to leukocytes involves", "protein to leukocytes involves the", "to leukocytes involves the host", "leukocytes involves the host cx3c", "involves the host cx3c chemokine", "the host cx3c chemokine receptor", "host cx3c chemokine receptor 1", "chemokine receptor 1 cx3cr1", "1 cx3cr1 and", "cx3cr1 and results in", "and results in blocking signaling", "results in blocking signaling and", "in blocking signaling and trafficking", "blocking signaling and trafficking of", "signaling and trafficking of cx3cr1", "and trafficking of cx3cr1 expressing", "trafficking of cx3cr1 expressing th1", "of cx3cr1 expressing th1 immune", "cx3cr1 expressing th1 immune cells", "expressing th1 immune cells to", "th1 immune cells to the", "immune cells to the lungs", "to the lungs facilitating", "the lungs facilitating rsv", "lungs facilitating rsv infection", "facilitating rsv infection harcourt", "rsv infection harcourt et", "infection harcourt et al.", "harcourt et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the hrsv ns2", ". the hrsv ns2 protein", "the hrsv ns2 protein induces", "hrsv ns2 protein induces cell", "ns2 protein induces cell shedding", "protein induces cell shedding into", "induces cell shedding into large", "cell shedding into large airways", "shedding into large airways causing", "into large airways causing an", "large airways causing an acute", "airways causing an acute airway", "causing an acute airway obstruction", "an acute airway obstruction in", "acute airway obstruction in an", "airway obstruction in an animal", "obstruction in an animal model", "in an animal model of", "an animal model of rsv", "animal model of rsv infection", "model of rsv infection through", "of rsv infection through an", "rsv infection through an unknown", "infection through an unknown mechanism", "an unknown mechanism liesman", "unknown mechanism liesman et", "mechanism liesman et al.", "liesman et al. 2014", "et al. 2014 .", "al. 2014 .

              several", "2014 .

              several host factors", ".

              several host factors contribute", "

              several host factors contribute to", "host factors contribute to the", "factors contribute to the pathogenesis", "contribute to the pathogenesis of", "to the pathogenesis of rsv", "the pathogenesis of rsv infection", "pathogenesis of rsv infection and", "of rsv infection and its", "rsv infection and its long", "infection and its long term", "and its long term effects", "long term effects including", "term effects including age", "age prematurity underlying", "prematurity underlying respiratory conditions", "underlying respiratory conditions such as", "respiratory conditions such as chronic", "conditions such as chronic lung", "such as chronic lung disease", "as chronic lung disease including", "chronic lung disease including cystic", "lung disease including cystic fibrosis", "including cystic fibrosis deficiencies", "cystic fibrosis deficiencies in", "fibrosis deficiencies in specific", "deficiencies in specific immune components", "in specific immune components or", "specific immune components or dysregulated", "immune components or dysregulated immune", "components or dysregulated immune responses", "dysregulated immune responses reviewed", "immune responses reviewed by", "responses reviewed by carvajal", "reviewed by carvajal et al.", "carvajal et al. 2019", "et al. 2019 .", "al. 2019 . in", "2019 . in some cases", "in some cases an", "some cases an exaggerated", "cases an exaggerated immune", "an exaggerated immune response to", "exaggerated immune response to rsv", "immune response to rsv infection", "response to rsv infection can", "to rsv infection can affect", "rsv infection can affect the", "infection can affect the host's", "can affect the host's ability", "affect the host's ability to", "the host's ability to control", "host's ability to control viral", "ability to control viral infection", "to control viral infection leading", "control viral infection leading to", "viral infection leading to immunopathology.", "infection leading to immunopathology. for", "leading to immunopathology. for example", "immunopathology. for example elevated", "for example elevated production", "example elevated production of", "elevated production of th2 type", "production of th2 type cytokines", "th2 type cytokines il", "type cytokines il 4", "il 4 il 5", "4 il 5 and", "il 5 and il 13", "and il 13 in", "il 13 in response", "13 in response to", "response to rsv infection leads", "to rsv infection leads to", "rsv infection leads to airway", "infection leads to airway hyperreactivity", "leads to airway hyperreactivity and", "to airway hyperreactivity and increased", "airway hyperreactivity and increased risk", "hyperreactivity and increased risk of", "and increased risk of developing", "increased risk of developing asthma", "risk of developing asthma after", "of developing asthma after hrsv", "developing asthma after hrsv infection", "after hrsv infection vu", "hrsv infection vu et", "infection vu et al.", "vu et al. 2019", "al. 2019 dong", "2019 dong et al.", "dong et al. 2023", "al. 2023 reviewed", "2023 reviewed by norlander", "reviewed by norlander & peebles", "by norlander & peebles 2020", "& peebles 2020 manti", "peebles 2020 manti &", "2020 manti & piedimonte", "manti & piedimonte 2022 .", "& piedimonte 2022 . the", "piedimonte 2022 . the outcome", "2022 . the outcome of", ". the outcome of rsv", "the outcome of rsv infection", "outcome of rsv infection depends", "of rsv infection depends on", "rsv infection depends on a", "infection depends on a complex", "depends on a complex interplay", "on a complex interplay between", "a complex interplay between the", "complex interplay between the immune", "interplay between the immune responses", "between the immune responses induced", "the immune responses induced by", "immune responses induced by the", "responses induced by the host", "induced by the host and", "by the host and the", "the host and the strategies", "host and the strategies developed", "and the strategies developed by", "the strategies developed by rsv", "strategies developed by rsv to", "developed by rsv to subvert", "by rsv to subvert these", "rsv to subvert these responses.

              this", "to subvert these responses.

              this reactome", "subvert these responses.

              this reactome module", "these responses.

              this reactome module describes", "responses.

              this reactome module describes molecular", "reactome module describes molecular mechanisms", "module describes molecular mechanisms by", "describes molecular mechanisms by which", "molecular mechanisms by which specific", "mechanisms by which specific rsv", "by which specific rsv components", "which specific rsv components modulate", "specific rsv components modulate innate", "rsv components modulate innate and", "components modulate innate and adaptive", "modulate innate and adaptive immune", "innate and adaptive immune responses", "adaptive immune responses programmed", "immune responses programmed cell", "responses programmed cell death", "programmed cell death and", "cell death and host", "death and host gene" ] }, { "record_id": "GLY_000594_1_2123", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9845576", "r hsa", "hsa 9845576", "r hsa 9845576" ] }, { "record_id": "GLY_000594_1_2123", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "glycosphingolipid transport", "after biosynthesis", "biosynthesis on", "on the", "the golgi", "golgi membrane", "gangliosides localize", "localize to", "to other", "other membranes", "membranes via", "via vesicle", "vesicle transport", "and exocytosis.", "exocytosis. to", "to decouple", "decouple transport", "transport from", "from vesicular", "vesicular transport", "transport of", "of proteins", "gangliosides are", "are additionally", "additionally transported", "transported via", "via non", "non vesicular", "vesicular processes", "reviewed by", "by perry", "perry &", "& ridgway", "funato et", "et al.", "2020 .", "after biosynthesis on", "biosynthesis on the", "on the golgi", "the golgi membrane", "membrane gangliosides", "gangliosides localize to", "localize to other", "to other membranes", "other membranes via", "membranes via vesicle", "via vesicle transport", "transport endocytosis", "endocytosis and", "and exocytosis. to", "exocytosis. to decouple", "to decouple transport", "decouple transport from", "transport from vesicular", "from vesicular transport", "vesicular transport of", "transport of proteins", "proteins gangliosides", "gangliosides are additionally", "are additionally transported", "additionally transported via", "transported via non", "via non vesicular", "non vesicular processes", "processes reviewed", "reviewed by perry", "by perry &", "perry & ridgway", "ridgway 2005", "2005 funato", "funato et al.", "al. 2020", "after biosynthesis on the", "biosynthesis on the golgi", "on the golgi membrane", "golgi membrane gangliosides", "membrane gangliosides localize", "gangliosides localize to other", "localize to other membranes", "to other membranes via", "other membranes via vesicle", "membranes via vesicle transport", "vesicle transport endocytosis", "endocytosis and exocytosis.", "and exocytosis. to decouple", "exocytosis. to decouple transport", "to decouple transport from", 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exocytosis. to decouple transport", "exocytosis. to decouple transport from", "to decouple transport from vesicular", "decouple transport from vesicular transport", "transport from vesicular transport of", "from vesicular transport of proteins", "transport of proteins gangliosides", "of proteins gangliosides are", "proteins gangliosides are additionally", "gangliosides are additionally transported via", "are additionally transported via non", "additionally transported via non vesicular", "transported via non vesicular processes", "non vesicular processes reviewed", "vesicular processes reviewed by", "processes reviewed by perry", "reviewed by perry & ridgway", "perry & ridgway 2005", "ridgway 2005 funato", "2005 funato et al.", "funato et al. 2020", "et al. 2020 ." ] }, { "record_id": "GLY_000594_1_2124", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9856532", "r hsa", "hsa 9856532", "r hsa 9856532" ] }, { "record_id": "GLY_000594_1_2124", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mechanical load", "load activates", "activates signaling", "signaling by", "by piezo1", "piezo1 and", "and integrins", "integrins in", "in osteocytes", "mechanical load activates", "load activates signaling", "activates signaling by", "signaling by piezo1", "by piezo1 and", "piezo1 and integrins", "and integrins in", "integrins in osteocytes", "mechanical load activates signaling", "load activates signaling by", "activates signaling by piezo1", "signaling by piezo1 and", "by piezo1 and integrins", "piezo1 and integrins in", "and integrins in osteocytes", "mechanical load activates signaling by", "load activates signaling by piezo1", "activates signaling by piezo1 and", "signaling by piezo1 and integrins", "by piezo1 and integrins in", "piezo1 and integrins in osteocytes", "osteocytes are", "are mechanosensory", "mechanosensory cells", "cells in", "in mineralized", "mineralized bone", "bone that", "that have", "have dendrites", "dendrites extending", "extending through", "through lacunae", "parallel with", "with collagen", "collagen fibers", "and canaliculi", "perpendicular to", "to collagen", "to make", "make contact", "contact with", "with other", "other osteocytes", "osteocytes and", "and with", "with osteoblasts", "osteoblasts on", "on the", "the bone", "bone surface", "reviewed in", "in moriishi", "moriishi and", "and komori", "komori 2022", "2022 .", ". fluid", "fluid flow", "flow and", "and pressure", "pressure in", "in the", "the lacunae", "lacunae and", "canaliculi are", "are sensed", "sensed by", "by the", "the dendrites", "dendrites and", "and communicated", "communicated to", "to the", "the cell", "cell body", "inferred from", "from mouse", "mouse osteocytes", "osteocytes in", "in burra", "burra et", "et al.", "al. 2010", "resulting in", "in secretion", "secretion of", "of anabolic", "anabolic factors", "factors such", "such as", "as prostaglandin", "prostaglandin e2", "that act", "act to", "to strengthen", "strengthen the", "siller jackson", "jackson et", "al. 2008", "riquelme et", "al. 2021", "in zhao", "zhao et", "al. 2023", "2023 .
              mechanosensitive", ".
              mechanosensitive piezo1", "piezo1 channels", "channels are", "are opened", "opened by", "by membrane", "membrane stretch", "stretch and", "and transport", "transport calcium", "calcium and", "and sodium", "sodium ions", "ions along", "along their", "their concentration", "concentration gradients", "gradients into", "into the", "the osteocyte.", "osteocyte. t", "t type", "type voltage", "voltage sensitive", "sensitive calcium", "calcium channels", "cav2 channles", "open secondarily", "secondarily and", "and augment", "augment the", "the calcium", "calcium influx.", "influx. cytosolic", "cytosolic calcium", "calcium activates", "activates pannexin", "pannexin 1", "which transport", "transport atp", "atp from", "from the", "the cytosol", "cytosol to", "the extracellular", "extracellular region.", "region. extracellular", "extracellular atp", "atp binds", "binds p2rx7", "receptors located", "located in", "in a", "a complex", "complex with", "with panx1.", "panx1. p2rx7", "p2rx7 then", "then transports", "transports cations", "cations including", "including calcium", "calcium into", "cell and", "and may", "may act", "act in", "in an", "an autocrine", "autocrine and", "and paracrine", "paracrine manner", "manner to", "to propagate", "propagate waves", "waves of", "of calcium", "calcium influx.
              integrin", "influx.
              integrin alphav:beta3", "the plasma", "plasma membrane", "membrane of", "of dendrites", "dendrites binds", "binds the", "extracellular matrix", "matrix of", "of the", "the lacunar", "lacunar or", "or canicular", "canicular wall.", "wall. fluid", "flow activates", "activates itgav:itgb3", "itgav:itgb3 to", "to phosphorylate", "phosphorylate akt1", "akt1 via", "via a", "a pi3k", "pi3k dependent", "dependent mechanism", "2021 .", ". phospho", "phospho akt1", "akt1 then", "then phosphorylates", "phosphorylates integrin", "integrin alpha5", "and connexin43", "complex in", "cell body.", "body. phospho", "phospho gja1", "gja1 transports", "transports atp", "kang et", "and pge2", "pge2 from", "extracellular region", "2023 .
              cav3.2", ".
              cav3.2 voltage", "channels also", "also directly", "directly interact", "interact with", "with the", "extracellular proteoglycan", "proteoglycan perlecan", "and the", "the alpha2delta1", "alpha2delta1 subunit", "subunit of", "the cav3.2", "cav3.2 complex", "reyes fernandez", "fernandez et", "al. 2022", ". physical", "physical force", "force on", "on perlecan", "perlecan may", "may thus", "thus affect", "affect calcium", "calcium transport", "transport by", "cav3.2 channels.", "osteocytes are mechanosensory", "are mechanosensory cells", "mechanosensory cells in", "cells in mineralized", "in mineralized bone", "mineralized bone that", "bone that have", "that have dendrites", "have dendrites extending", "dendrites extending through", "extending through lacunae", "lacunae parallel", "parallel with collagen", "with collagen fibers", "fibers and", "canaliculi perpendicular", "perpendicular to collagen", "to collagen fibers", "fibers to", "to make contact", "make contact with", "contact with other", "with other osteocytes", "other osteocytes and", "osteocytes and with", "and with osteoblasts", "with osteoblasts on", "osteoblasts on the", "on the bone", "the bone surface", "surface reviewed", "reviewed in moriishi", "in moriishi and", "moriishi and komori", "and komori 2022", "komori 2022 .", "2022 . fluid", ". fluid flow", "fluid flow and", "flow and pressure", "and pressure in", "pressure in the", "in the lacunae", "the lacunae and", "lacunae and canaliculi", "and canaliculi are", "canaliculi are sensed", "are sensed by", "sensed by the", "by the dendrites", "the dendrites and", "dendrites and communicated", "and communicated to", "communicated to the", "to the cell", "the cell body", "body inferred", "inferred from mouse", "from mouse osteocytes", "mouse osteocytes in", "osteocytes in burra", "in burra et", "burra et al.", "et al. 2010", "resulting in secretion", "in secretion of", "secretion of anabolic", "of anabolic factors", "anabolic factors such", "factors such as", "such as prostaglandin", "as prostaglandin e2", "e2 pge2", "pge2 that", "that act to", "act to strengthen", "to strengthen the", "strengthen the bone", "bone siller", "siller jackson et", "jackson et al.", "et al. 2008", "2008 riquelme", "riquelme et al.", "et al. 2021", "2021 reviewed", "reviewed in zhao", "in zhao et", "zhao et al.", "et al. 2023", "al. 2023 .
              mechanosensitive", "2023 .
              mechanosensitive piezo1", ".
              mechanosensitive piezo1 channels", "piezo1 channels are", "channels are opened", "are opened by", "opened by membrane", "by membrane stretch", "membrane stretch and", "stretch and transport", "and transport calcium", "transport calcium and", "calcium and sodium", "and sodium ions", "sodium ions along", "ions along their", "along their concentration", "their concentration gradients", "concentration gradients into", "gradients into the", "into the osteocyte.", "the osteocyte. t", "osteocyte. t type", "t type voltage", "type voltage sensitive", "voltage sensitive calcium", "sensitive calcium channels", "channels cav2", "channles open", "open secondarily and", "secondarily and augment", "and augment the", "augment the calcium", "the calcium influx.", "calcium influx. cytosolic", "influx. cytosolic calcium", "cytosolic calcium activates", "calcium activates pannexin", "activates pannexin 1", "1 panx1", "panx1 channels", "channels which", "which transport atp", "transport atp from", "atp from the", "from the cytosol", "the cytosol to", "cytosol to the", "to the extracellular", "the extracellular region.", "extracellular region. extracellular", "region. extracellular atp", "extracellular atp binds", "atp binds p2rx7", "p2rx7 p2x7", "p2x7 receptors", "receptors located in", "located in a", "in a complex", "a complex with", "complex with panx1.", "with panx1. p2rx7", "panx1. p2rx7 then", "p2rx7 then transports", "then transports cations", "transports cations including", "cations including calcium", "including calcium into", "calcium into the", "into the cell", "the cell and", "cell and may", "and may act", "may act in", "act in an", "in an autocrine", "an autocrine and", "autocrine and paracrine", "and paracrine manner", "paracrine manner to", "manner to propagate", "to propagate waves", "propagate waves of", "waves of calcium", "of calcium influx.
              integrin", "calcium influx.
              integrin alphav:beta3", "alphav:beta3 itgav:itgb3", "itgav:itgb3 located", "located in the", "in the plasma", "the plasma membrane", "plasma membrane of", "membrane of dendrites", "of dendrites binds", "dendrites binds the", "binds the extracellular", "the extracellular matrix", "extracellular matrix of", "matrix of the", "of the lacunar", "the lacunar or", "lacunar or canicular", "or canicular wall.", "canicular wall. fluid", "wall. fluid flow", "fluid flow activates", "flow activates itgav:itgb3", "activates itgav:itgb3 to", "itgav:itgb3 to phosphorylate", "to phosphorylate akt1", "phosphorylate akt1 via", "akt1 via a", "via a pi3k", "a pi3k dependent", "pi3k dependent mechanism", "mechanism riquelme", "al. 2021 .", "2021 . phospho", ". phospho akt1", "phospho akt1 then", "akt1 then phosphorylates", "then phosphorylates integrin", "phosphorylates integrin alpha5", "alpha5 itga5", "itga5 and", "connexin43 gja1", "gja1 located", "a complex in", "complex in the", "membrane of the", "of the cell", "the cell body.", "cell body. phospho", "body. phospho gja1", "phospho gja1 transports", "gja1 transports atp", "atp kang", "kang et al.", "2008 and", "and pge2 from", "pge2 from the", "the extracellular region", "region reviewed", "al. 2023 .
              cav3.2", "2023 .
              cav3.2 voltage", ".
              cav3.2 voltage sensitive", "calcium channels also", "channels also directly", "also directly interact", "directly interact with", "interact with the", "with the extracellular", "the extracellular proteoglycan", "extracellular proteoglycan perlecan", "perlecan pln", "pln plc", "plc hspg2", "hspg2 and", "and the alpha2delta1", "the alpha2delta1 subunit", "alpha2delta1 subunit of", "subunit of the", "of the cav3.2", "the cav3.2 complex", "complex reyes", "reyes fernandez et", "fernandez et al.", "et al. 2022", "al. 2022 .", "2022 . physical", ". physical force", "physical force on", "force on perlecan", "on perlecan may", "perlecan may thus", "may thus affect", "thus affect calcium", "affect calcium transport", "calcium transport by", "transport by the", "by the cav3.2", "the cav3.2 channels.", "osteocytes are mechanosensory cells", "are mechanosensory cells in", "mechanosensory cells in mineralized", "cells in mineralized bone", "in mineralized bone that", "mineralized bone that have", "bone that have dendrites", "that have dendrites extending", "have dendrites extending through", "dendrites extending through lacunae", "through lacunae parallel", "lacunae parallel with", "parallel with collagen fibers", "collagen fibers and", "fibers and canaliculi", "and canaliculi perpendicular", "canaliculi perpendicular to", "perpendicular to collagen fibers", "collagen fibers to", "fibers to make", "to make contact with", "make contact with other", "contact with other osteocytes", "with other osteocytes and", "other osteocytes and with", "osteocytes and with osteoblasts", "and with osteoblasts on", "with osteoblasts on the", "osteoblasts on the bone", "on the bone surface", "bone surface reviewed", "surface reviewed in", "reviewed in moriishi and", "in moriishi and komori", "moriishi and komori 2022", "and komori 2022 .", "komori 2022 . fluid", "2022 . fluid flow", ". fluid flow and", "fluid flow and pressure", "flow and pressure in", "and pressure in the", "pressure in the lacunae", "in the lacunae and", "the lacunae and canaliculi", "lacunae and canaliculi are", "and canaliculi are sensed", "canaliculi are sensed by", "are sensed by the", "sensed by the dendrites", "by the dendrites and", "the dendrites and communicated", "dendrites and communicated to", "and communicated to the", "communicated to the cell", "to the cell body", "cell body inferred", "body inferred from", "inferred from mouse osteocytes", "from mouse osteocytes in", "mouse osteocytes in burra", "osteocytes in burra et", "in burra et al.", "burra et al. 2010", "2010 resulting", "resulting in secretion of", "in secretion of anabolic", "secretion of anabolic factors", "of anabolic factors such", "anabolic factors such as", "factors such as prostaglandin", "such as prostaglandin e2", "prostaglandin e2 pge2", "pge2 that act", "that act to strengthen", "act to strengthen the", "to strengthen the bone", "the bone siller", "bone siller jackson", "siller jackson et al.", "jackson et al. 2008", "al. 2008 riquelme", "2008 riquelme et", "riquelme et al. 2021", "al. 2021 reviewed", "2021 reviewed in", "reviewed in zhao et", "in zhao et al.", "zhao et al. 2023", "et al. 2023 .
              mechanosensitive", "al. 2023 .
              mechanosensitive piezo1", "2023 .
              mechanosensitive piezo1 channels", ".
              mechanosensitive piezo1 channels are", "piezo1 channels are opened", "channels are opened by", "are opened by membrane", "opened by membrane stretch", "by membrane stretch and", "membrane stretch and transport", "stretch and transport calcium", "and transport calcium and", "transport calcium and sodium", "calcium and sodium ions", "and sodium ions along", "sodium ions along their", "ions along their concentration", "along their concentration gradients", "their concentration gradients into", "concentration gradients into the", "gradients into the osteocyte.", "into the osteocyte. t", "the osteocyte. t type", "osteocyte. t type voltage", "t type voltage sensitive", "type voltage sensitive calcium", "voltage sensitive calcium channels", "calcium channels cav2", "channels cav2 channles", "cav2 channles open", "channles open secondarily", "open secondarily and augment", "secondarily and augment the", "and augment the calcium", "augment the calcium influx.", "the calcium influx. cytosolic", "calcium influx. cytosolic calcium", "influx. cytosolic calcium activates", "cytosolic calcium activates pannexin", "calcium activates pannexin 1", "pannexin 1 panx1", "channels which transport", "which transport atp from", "transport atp from the", "atp from the cytosol", "from the cytosol to", "the cytosol to the", "cytosol to the extracellular", "to the extracellular region.", "the extracellular region. extracellular", "extracellular region. extracellular atp", "region. extracellular atp binds", "extracellular atp binds p2rx7", "binds p2rx7 p2x7", "p2x7 receptors located", "receptors located in a", "located in a complex", "in a complex with", "a complex with panx1.", "complex with panx1. p2rx7", "with panx1. p2rx7 then", "panx1. p2rx7 then transports", "p2rx7 then transports cations", "then transports cations including", "transports cations including calcium", "cations including calcium into", "including calcium into the", "calcium into the cell", "into the cell and", "the cell and may", "cell and may act", "and may act in", "may act in an", "act in an autocrine", "in an autocrine and", "an autocrine and paracrine", "autocrine and paracrine manner", "and paracrine manner to", "paracrine manner to propagate", "manner to propagate waves", "to propagate waves of", "propagate waves of calcium", "waves of calcium influx.
              integrin", "of calcium influx.
              integrin alphav:beta3", "influx.
              integrin alphav:beta3 itgav:itgb3", "itgav:itgb3 located in", "located in the plasma", "in the plasma membrane", "the plasma membrane of", "plasma membrane of dendrites", "membrane of dendrites binds", "of dendrites binds the", "dendrites binds the extracellular", "binds the extracellular matrix", "the extracellular matrix of", "extracellular matrix of the", "matrix of the lacunar", "of the lacunar or", "the lacunar or canicular", "lacunar or canicular wall.", "or canicular wall. fluid", "canicular wall. fluid flow", "wall. fluid flow activates", "fluid flow activates itgav:itgb3", "flow activates itgav:itgb3 to", "activates itgav:itgb3 to phosphorylate", "itgav:itgb3 to phosphorylate akt1", "to phosphorylate akt1 via", "phosphorylate akt1 via a", "akt1 via a pi3k", "via a pi3k dependent", "a pi3k dependent mechanism", "dependent mechanism riquelme", "mechanism riquelme et", "et al. 2021 .", "al. 2021 . phospho", "2021 . phospho akt1", ". phospho akt1 then", "phospho akt1 then phosphorylates", "akt1 then phosphorylates integrin", "then phosphorylates integrin alpha5", "integrin alpha5 itga5", "itga5 and connexin43", "and connexin43 gja1", "gja1 located in", "in a complex in", "a complex in the", "complex in the plasma", "plasma membrane of the", "membrane of the cell", "of the cell body.", "the cell body. phospho", "cell body. phospho gja1", "body. phospho gja1 transports", "phospho gja1 transports atp", "transports atp kang", "atp kang et", "kang et al. 2008", "al. 2008 and", "2008 and pge2", "and pge2 from the", "pge2 from the cytosol", "to the extracellular region", "extracellular region reviewed", "region reviewed in", "et al. 2023 .
              cav3.2", "al. 2023 .
              cav3.2 voltage", "2023 .
              cav3.2 voltage sensitive", ".
              cav3.2 voltage sensitive calcium", "sensitive calcium channels also", "calcium channels also directly", "channels also directly interact", "also directly interact with", "directly interact with the", "interact with the extracellular", "with the extracellular proteoglycan", "the extracellular proteoglycan perlecan", "proteoglycan perlecan pln", "hspg2 and the", "and the alpha2delta1 subunit", "the alpha2delta1 subunit of", "alpha2delta1 subunit of the", "subunit of the cav3.2", "of the cav3.2 complex", "cav3.2 complex reyes", "complex reyes fernandez", "reyes fernandez et al.", "fernandez et al. 2022", "et al. 2022 .", "al. 2022 . physical", "2022 . physical force", ". physical force on", "physical force on perlecan", "force on perlecan may", "on perlecan may thus", "perlecan may thus affect", "may thus affect calcium", "thus affect calcium transport", "affect calcium transport by", "calcium transport by the", "transport by the cav3.2", "by the cav3.2 channels.", "osteocytes are mechanosensory cells in", "are mechanosensory cells in mineralized", "mechanosensory cells in mineralized bone", "cells in mineralized bone that", "in mineralized bone that have", "mineralized bone that have dendrites", "bone that have dendrites extending", "that have dendrites extending through", "have dendrites extending through lacunae", "extending through lacunae parallel", "through lacunae parallel with", "lacunae parallel with collagen", "with collagen fibers and", "collagen fibers and canaliculi", "and canaliculi perpendicular to", "canaliculi perpendicular to collagen", "to collagen fibers to", "collagen fibers to make", "fibers to make contact", "to make contact with other", "make contact with other osteocytes", "contact with other osteocytes and", "with other osteocytes and with", "other osteocytes and with osteoblasts", "osteocytes and with osteoblasts on", "and with osteoblasts on the", "with osteoblasts on the bone", "osteoblasts on the bone surface", "the bone surface reviewed", "bone surface reviewed in", "surface reviewed in moriishi", "reviewed in moriishi and komori", "in moriishi and komori 2022", "moriishi and komori 2022 .", "and komori 2022 . fluid", "komori 2022 . fluid flow", "2022 . fluid flow and", ". fluid flow and pressure", "fluid flow and pressure in", "flow and pressure in the", "and pressure in the lacunae", "pressure in the lacunae and", "in the lacunae and canaliculi", "the lacunae and canaliculi are", "lacunae and canaliculi are sensed", "and canaliculi are sensed by", "canaliculi are sensed by the", "are sensed by the dendrites", "sensed by the dendrites and", "by the dendrites and communicated", "the dendrites and communicated to", "dendrites and communicated to the", "and communicated to the cell", "communicated to the cell body", "the cell body inferred", "cell body inferred from", "body inferred from mouse", "inferred from mouse osteocytes in", "from mouse osteocytes in burra", "mouse osteocytes in burra et", "osteocytes in burra et al.", "in burra et al. 2010", "al. 2010 resulting", "2010 resulting in", "resulting in secretion of anabolic", "in secretion of anabolic factors", "secretion of anabolic factors such", "of anabolic factors such as", "anabolic factors such as prostaglandin", "factors such as prostaglandin e2", "as prostaglandin e2 pge2", "e2 pge2 that", "pge2 that act to", "that act to strengthen the", "act to strengthen the bone", "strengthen the bone siller", "the bone siller jackson", "bone siller jackson et", "siller jackson et al. 2008", "et al. 2008 riquelme", "al. 2008 riquelme et", "2008 riquelme et al.", "et al. 2021 reviewed", "al. 2021 reviewed in", "2021 reviewed in zhao", "reviewed in zhao et al.", "in zhao et al. 2023", "zhao et al. 2023 .
              mechanosensitive", "et al. 2023 .
              mechanosensitive piezo1", "al. 2023 .
              mechanosensitive piezo1 channels", "2023 .
              mechanosensitive piezo1 channels are", ".
              mechanosensitive piezo1 channels are opened", "piezo1 channels are opened by", "channels are opened by membrane", "are opened by membrane stretch", "opened by membrane stretch and", "by membrane stretch and transport", "membrane stretch and transport calcium", "stretch and transport calcium and", "and transport calcium and sodium", "transport calcium and sodium ions", "calcium and sodium ions along", "and sodium ions along their", "sodium ions along their concentration", "ions along their concentration gradients", "along their concentration gradients into", "their concentration gradients into the", "concentration gradients into the osteocyte.", "gradients into the osteocyte. t", "into the osteocyte. t type", "the osteocyte. t type voltage", "osteocyte. t type voltage sensitive", "t type voltage sensitive calcium", "type voltage sensitive calcium channels", "sensitive calcium channels cav2", "calcium channels cav2 channles", "cav2 channles open secondarily", "channles open secondarily and", "open secondarily and augment the", "secondarily and augment the calcium", "and augment the calcium influx.", "augment the calcium influx. cytosolic", "the calcium influx. cytosolic calcium", "calcium influx. cytosolic calcium activates", "influx. cytosolic calcium activates pannexin", "cytosolic calcium activates pannexin 1", "activates pannexin 1 panx1", "1 panx1 channels", "panx1 channels which", "channels which transport atp", "which transport atp from the", "transport atp from the cytosol", "atp from the cytosol to", "from the cytosol to the", "the cytosol to the extracellular", "cytosol to the extracellular region.", "to the extracellular region. extracellular", "the extracellular region. extracellular atp", "extracellular region. extracellular atp binds", "region. extracellular atp binds p2rx7", "atp binds p2rx7 p2x7", "p2rx7 p2x7 receptors", "p2x7 receptors located in", "receptors located in a complex", "located in a complex with", "in a complex with panx1.", "a complex with panx1. p2rx7", "complex with panx1. p2rx7 then", "with panx1. p2rx7 then transports", "panx1. p2rx7 then transports cations", "p2rx7 then transports cations including", "then transports cations including calcium", "transports cations including calcium into", "cations including calcium into the", "including calcium into the cell", "calcium into the cell and", "into the cell and may", "the cell and may act", "cell and may act in", "and may act in an", "may act in an autocrine", "act in an autocrine and", "in an autocrine and paracrine", "an autocrine and paracrine manner", "autocrine and paracrine manner to", "and paracrine manner to propagate", "paracrine manner to propagate waves", "manner to propagate waves of", "to propagate waves of calcium", "propagate waves of calcium influx.
              integrin", "waves of calcium influx.
              integrin alphav:beta3", "calcium influx.
              integrin alphav:beta3 itgav:itgb3", "alphav:beta3 itgav:itgb3 located", "itgav:itgb3 located in the", "located in the plasma membrane", "in the plasma membrane of", "the plasma membrane of dendrites", "plasma membrane of dendrites binds", "membrane of dendrites binds the", "of dendrites binds the extracellular", "dendrites binds the extracellular matrix", "binds the extracellular matrix of", "the extracellular matrix of the", "extracellular matrix of the lacunar", "matrix of the lacunar or", "of the lacunar or canicular", "the lacunar or canicular wall.", "lacunar or canicular wall. fluid", "or canicular wall. fluid flow", "canicular wall. fluid flow activates", "wall. fluid flow activates itgav:itgb3", "fluid flow activates itgav:itgb3 to", "flow activates itgav:itgb3 to phosphorylate", "activates itgav:itgb3 to phosphorylate akt1", "itgav:itgb3 to phosphorylate akt1 via", "to phosphorylate akt1 via a", "phosphorylate akt1 via a pi3k", "akt1 via a pi3k dependent", "via a pi3k dependent mechanism", "pi3k dependent mechanism riquelme", "dependent mechanism riquelme et", "mechanism riquelme et al.", "riquelme et al. 2021 .", "et al. 2021 . phospho", "al. 2021 . phospho akt1", "2021 . phospho akt1 then", ". phospho akt1 then phosphorylates", "phospho akt1 then phosphorylates integrin", "akt1 then phosphorylates integrin alpha5", "phosphorylates integrin alpha5 itga5", "alpha5 itga5 and", "connexin43 gja1 located", "gja1 located in a", "located in a complex in", "in a complex in the", "a complex in the plasma", "complex in the plasma membrane", "the plasma membrane of the", "plasma membrane of the cell", "membrane of the cell body.", "of the cell body. phospho", "the cell body. phospho gja1", "cell body. phospho gja1 transports", "body. phospho gja1 transports atp", "gja1 transports atp kang", "transports atp kang et", "atp kang et al.", "et al. 2008 and", "al. 2008 and pge2", "2008 and pge2 from", "and pge2 from the cytosol", "pge2 from the cytosol to", "cytosol to the extracellular region", "the extracellular region reviewed", "extracellular region reviewed in", "region reviewed in zhao", "zhao et al. 2023 .
              cav3.2", "et al. 2023 .
              cav3.2 voltage", "al. 2023 .
              cav3.2 voltage sensitive", "2023 .
              cav3.2 voltage sensitive calcium", ".
              cav3.2 voltage sensitive calcium channels", "voltage sensitive calcium channels also", "sensitive calcium channels also directly", "calcium channels also directly interact", "channels also directly interact with", "also directly interact with the", "directly interact with the extracellular", "interact with the extracellular proteoglycan", "with the extracellular proteoglycan perlecan", "extracellular proteoglycan perlecan pln", "perlecan pln plc", "pln plc hspg2", "plc hspg2 and", "hspg2 and the alpha2delta1", "and the alpha2delta1 subunit of", "the alpha2delta1 subunit of the", "alpha2delta1 subunit of the cav3.2", "subunit of the cav3.2 complex", "the cav3.2 complex reyes", "cav3.2 complex reyes fernandez", "complex reyes fernandez et", "reyes fernandez et al. 2022", "fernandez et al. 2022 .", "et al. 2022 . physical", "al. 2022 . physical force", "2022 . physical force on", ". physical force on perlecan", "physical force on perlecan may", "force on perlecan may thus", "on perlecan may thus affect", "perlecan may thus affect calcium", "may thus affect calcium transport", "thus affect calcium transport by", "affect calcium transport by the", "calcium transport by the cav3.2", "transport by the cav3.2 channels." ] }, { "record_id": "GLY_000594_1_2125", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9911233", "r hsa", "hsa 9911233", "r hsa 9911233" ] }, { "record_id": "GLY_000594_1_2125", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "expression of", "of notch2nl", "notch2nl genes", "expression of notch2nl", "of notch2nl genes", "expression of notch2nl genes", "

              the notch2nl", "notch2nl gene", "gene family", "family includes", "includes four", "four genes", "and notch2nlr", "which originated", "originated from", "from the", "the partial", "partial duplication", "duplication of", "of the", "the first", "first four", "four exons", "exons and", "and introns", "introns of", "the notch2", "notch2 gene.", "gene. three", "three of", "the duplicated", "duplicated genes", "and notch2nlc", "reside at", "at the", "the chromosomal", "chromosomal band", "band 1q21.1", "while notch2nlr", "notch2nlr resides", "resides at", "at 1p12", "in the", "the vicinity", "vicinity of", "of notch2.", "notch2. notch2nla", "notch2nla was", "was originally", "originally cloned", "cloned as", "as a", "a gene", "gene highly", "highly expressed", "expressed in", "in white", "white blood", "blood cells", "duan et", "et al.", "al. 2004", "2004 .", ". several", "several studies", "studies suggest", "suggest that", "notch2nl genes", "genes may", "may have", "have played", "played a", "a role", "role in", "the evolutionary", "evolutionary expansion", "expansion of", "the human", "human brain", "florio et", "al. 2018", "fiddes et", "suzuki et", "lodewijk et", "al. 2020", "2020 .", ". notch2nl", "genes are", "are present", "present only", "only in", "the hominidae", "hominidae family", "family and", "while they", "they are", "are functional", "functional in", "in humans", "they exist", "exist as", "as pseudogenes", "pseudogenes in", "in chimpanzees", "chimpanzees and", "and gorillas.", "gorillas. in", "in addition", "these genes", "are highly", "expressed during", "during brain", "brain development", "and have", "have the", "the ability", "ability to", "to delay", "delay differentiation", "differentiation of", "of neuronal", "neuronal progenitors", "2018 .", ". the", "the study", "study of", "of sequence", "sequence polymorphism", "polymorphism and", "and copy", "copy number", "number variation", "variation in", "in notch2nl", "genes in", "in modern", "modern humans", "and comparative", "comparative analysis", "analysis of", "of notch2nl", "gene sequences", "sequences between", "between modern", "denisovans and", "and neanderthals", "is suggestive", "suggestive of", "of an", "an ongoing", "ongoing adaptive", "adaptive evolution", "evolution of", "of modern", "modern human", "human notch2nl", "genes trending", "trending toward", "toward lower", "lower levels", "levels of", "notch2nl proteins.", "proteins. downstream", "downstream of", "of each", "each of", "the notch2nl", "genes is", "is an", "an nbpf", "nbpf gene", "gene in", "the same", "same orientation", "orientation as", "as its", "its notch2nl", "notch2nl partner", "partner and", "and co", "co expressed", "expressed with", "with it", "nbpf10 downstream", "of notch2nla", "nbpf14 downstream", "of notch2nlb", "nbpf19 downstream", "of notch2nlc", "and nbpf26", "nbpf26 downstream", "of notch2nlr", "and these", "these notch2nl", "notch2nl nbpf", "nbpf pairs", "pairs likely", "likely function", "function in", "in a", "a coordinated", "complementary fashion", "fashion to", "to promote", "promote neurogenesis", "neurogenesis and", "and human", "brain expansion", "al. 2019", "2019 .

              the", ".

              the neurodevelopmental", "neurodevelopmental disorder", "disorder known", "known as", "as 1q21.1", "1q21.1 distal", "distal deletion/duplication", "deletion/duplication syndrome", "syndrome involves", "involves copy", "number gain", "gain or", "or loss", "loss of", "the 1q21.1", "1q21.1 chromosomal", "chromosomal region", "region that", "that includes", "includes notch2nla", "notch2nla and", "and notch2nlb", "notch2nlb genes.", "genes. copy", "number loss", "loss is", "is associated", "associated with", "with microcephaly", "while copy", "gain is", "with macrocephaly", "and both", "both gain", "gain and", "and loss", "loss are", "are accompanied", "accompanied with", "with severe", "severe neurological", "neurological disorders", ". breakpoints", "breakpoints within", "within notch2nl", "gene loci", "loci are", "are also", "also associated", "with neurological", "2020 .

              expansion", ".

              expansion of", "the ggc", "ggc repeat", "repeat in", "the 5\u2019utr", "5\u2019utr of", "the notch2nlc", "notch2nlc gene", "gene was", "was identified", "identified as", "as an", "an important", "important contributor", "contributor to", "to neuronal", "neuronal intranuclear", "intranuclear inclusion", "inclusion disease", "and may", "may play", "play a", "in other", "other neurodegenerative", "neurodegenerative disorders", "disorders such", "such as", "as parkinson\u2019s", "parkinson\u2019s disease", "alzheimer\u2019s disease", "frontotemporal dementia", "and amyotrophic", "amyotrophic lateral", "lateral sclerosis", "to name", "name a", "a few.", "few. the", "the underlying", "underlying pathogenic", "pathogenic mechanism", "mechanism has", "has not", "not been", "been elucidated.", "elucidated. for", "for review", "review of", "notch2nlc related", "related trinucleotide", "trinucleotide expansion", "expansion disorders", "please refer", "refer to", "to cao", "cao et", "al. 2021", "2021 and", "and huang", "huang et", "al. 2021.", "

              the notch2nl gene", "notch2nl gene family", "gene family includes", "family includes four", "includes four genes", "genes notch2nla", "notch2nla notch2nlb", "notch2nlb notch2nlc", "notch2nlc and", "notch2nlr which", "which originated from", "originated from the", "from the partial", "the partial duplication", "partial duplication of", "duplication of the", "of the first", "the first four", "first four exons", "four exons and", "exons and introns", "and introns of", "introns of the", "of the notch2", "the notch2 gene.", "notch2 gene. three", "gene. three of", "three of the", "of the duplicated", "the duplicated genes", "notch2nlb and", "notch2nlc reside", "reside at the", "at the chromosomal", "the chromosomal band", "chromosomal band 1q21.1", "1q21.1 while", "while notch2nlr resides", "notch2nlr resides at", "resides at 1p12", "1p12 in", "in the vicinity", "the vicinity of", "vicinity of notch2.", "of notch2. notch2nla", "notch2. notch2nla was", "notch2nla was originally", "was originally cloned", "originally cloned as", "cloned as a", "as a gene", "a gene highly", "gene highly expressed", "highly expressed in", "expressed in white", "in white blood", "white blood cells", "cells duan", "duan et al.", "et al. 2004", "al. 2004 .", "2004 . several", ". several studies", "several studies suggest", "studies suggest that", "that notch2nl", "notch2nl genes may", "genes may have", "may have played", "have played a", "played a role", "a role in", "role in the", "in the evolutionary", "the evolutionary expansion", "evolutionary expansion of", "expansion of the", "of the human", "the human brain", "brain florio", "florio et al.", "et al. 2018", "2018 fiddes", "fiddes et al.", "2018 suzuki", "suzuki et al.", "2018 lodewijk", "lodewijk et al.", "et al. 2020", "al. 2020 .", "2020 . notch2nl", ". notch2nl genes", "notch2nl genes are", "genes are present", "are present only", "present only in", "only in the", "in the hominidae", "the hominidae family", "hominidae family and", "and while", "while they are", "they are functional", "are functional in", "functional in humans", "humans they", "they exist as", "exist as pseudogenes", "as pseudogenes in", "pseudogenes in chimpanzees", "in chimpanzees and", "chimpanzees and gorillas.", "and gorillas. in", "gorillas. in addition", "addition these", "these genes are", "genes are highly", "are highly expressed", "highly expressed during", "expressed during brain", "during brain development", "development florio", "2018 and", "and have the", "have the ability", "the ability to", "ability to delay", "to delay differentiation", "delay differentiation of", "differentiation of neuronal", "of neuronal progenitors", "progenitors fiddes", "al. 2018 .", "2018 . the", ". the study", "the study of", "study of sequence", "of sequence polymorphism", "sequence polymorphism and", "polymorphism and copy", "and copy number", "copy number variation", "number variation in", "variation in notch2nl", "in notch2nl genes", "notch2nl genes in", "genes in modern", "in modern humans", "humans fiddes", "and comparative analysis", "comparative analysis of", "analysis of notch2nl", "of notch2nl gene", "notch2nl gene sequences", "gene sequences between", "sequences between modern", "between modern humans", "humans denisovans", "denisovans and neanderthals", "neanderthals lodewijk", "is suggestive of", "suggestive of an", "of an ongoing", "an ongoing adaptive", "ongoing adaptive evolution", "adaptive evolution of", "evolution of modern", "of modern human", "modern human notch2nl", "human notch2nl genes", "notch2nl genes trending", "genes trending toward", "trending toward lower", "toward lower levels", "lower levels of", "levels of notch2nl", "of notch2nl proteins.", "notch2nl proteins. downstream", "proteins. downstream of", "downstream of each", "of each of", "each of the", "of the notch2nl", "the notch2nl genes", "notch2nl genes is", "genes is an", "is an nbpf", "an nbpf gene", "nbpf gene in", "gene in the", "in the same", "the same orientation", "same orientation as", "orientation as its", "as its notch2nl", "its notch2nl partner", "notch2nl partner and", "partner and co", "and co expressed", "co expressed with", "expressed with it", "it nbpf10", "nbpf10 downstream of", "downstream of notch2nla", "notch2nla nbpf14", "nbpf14 downstream of", "downstream of notch2nlb", "notch2nlb nbpf19", "nbpf19 downstream of", "downstream of notch2nlc", "and nbpf26 downstream", "nbpf26 downstream of", "downstream of notch2nlr", "and these notch2nl", "these notch2nl nbpf", "notch2nl nbpf pairs", "nbpf pairs likely", "pairs likely function", "likely function in", "function in a", "in a coordinated", "coordinated complementary", "complementary fashion to", "fashion to promote", "to promote neurogenesis", "promote neurogenesis and", "neurogenesis and human", "and human brain", "human brain expansion", "expansion fiddes", "et al. 2019", "al. 2019 .

              the", "2019 .

              the neurodevelopmental", ".

              the neurodevelopmental disorder", "neurodevelopmental disorder known", "disorder known as", "known as 1q21.1", "as 1q21.1 distal", "1q21.1 distal deletion/duplication", "distal deletion/duplication syndrome", "deletion/duplication syndrome involves", "syndrome involves copy", "involves copy number", "copy number gain", "number gain or", "gain or loss", "or loss of", "loss of the", "of the 1q21.1", "the 1q21.1 chromosomal", "1q21.1 chromosomal region", "chromosomal region that", "region that includes", "that includes notch2nla", "includes notch2nla and", "notch2nla and notch2nlb", "and notch2nlb genes.", "notch2nlb genes. copy", "genes. copy number", "copy number loss", "number loss is", "loss is associated", "is associated with", "associated with microcephaly", "microcephaly while", "while copy number", "number gain is", "gain is associated", "associated with macrocephaly", "macrocephaly fiddes", "and both gain", "both gain and", "gain and loss", "and loss are", "loss are accompanied", "are accompanied with", "accompanied with severe", "with severe neurological", "severe neurological disorders", "disorders fiddes", "2020 . breakpoints", ". breakpoints within", "breakpoints within notch2nl", "within notch2nl gene", "notch2nl gene loci", "gene loci are", "loci are also", "are also associated", "also associated with", "associated with neurological", "with neurological disorders", "disorders lodewijk", "al. 2020 .

              expansion", "2020 .

              expansion of", ".

              expansion of the", "of the ggc", "the ggc repeat", "ggc repeat in", "repeat in the", "in the 5\u2019utr", "the 5\u2019utr of", "5\u2019utr of the", "of the notch2nlc", "the notch2nlc gene", "notch2nlc gene was", "gene was identified", "was identified as", "identified as an", "as an important", "an important contributor", "important contributor to", "contributor to neuronal", "to neuronal intranuclear", "neuronal intranuclear inclusion", "intranuclear inclusion disease", "disease niid", "niid and", "and may play", "may play a", "play a role", "role in other", "in other neurodegenerative", "other neurodegenerative disorders", "neurodegenerative disorders such", "disorders such as", "such as parkinson\u2019s", "as parkinson\u2019s disease", "disease alzheimer\u2019s", "disease frontotemporal", "dementia ftd", "and amyotrophic lateral", "amyotrophic lateral sclerosis", "sclerosis als", "to name a", "name a few.", "a few. the", "few. the underlying", "the underlying pathogenic", "underlying pathogenic mechanism", "pathogenic mechanism has", "mechanism has not", "has not been", "not been elucidated.", "been elucidated. for", "elucidated. for review", "for review of", "review of notch2nlc", "of notch2nlc related", "notch2nlc related trinucleotide", "related trinucleotide expansion", "trinucleotide expansion disorders", "disorders please", "please refer to", "refer to cao", "to cao et", "cao et al.", "et al. 2021", "al. 2021 and", "2021 and huang", "and huang et", "huang et al.", "et al. 2021.", "

              the notch2nl gene family", "notch2nl gene family includes", "gene family includes four", "family includes four genes", "four genes notch2nla", "notch2nlc and notch2nlr", "and notch2nlr which", "notch2nlr which originated", "which originated from the", "originated from the partial", "from the partial duplication", "the partial duplication of", "partial duplication of the", "duplication of the first", "of the first four", "the first four exons", "first four exons and", "four exons and introns", "exons and introns of", "and introns of the", "introns of the notch2", "of the notch2 gene.", "the notch2 gene. three", "notch2 gene. three of", "gene. three of the", "three of the duplicated", "of the duplicated genes", "duplicated genes notch2nla", "notch2nlb and notch2nlc", "and notch2nlc reside", "notch2nlc reside at", "reside at the chromosomal", "at the chromosomal band", "the chromosomal band 1q21.1", "band 1q21.1 while", "1q21.1 while notch2nlr", "while notch2nlr resides at", "notch2nlr resides at 1p12", "at 1p12 in", "1p12 in the", "in the vicinity of", "the vicinity of notch2.", "vicinity of notch2. notch2nla", "of notch2. notch2nla was", "notch2. notch2nla was originally", "notch2nla was originally cloned", "was originally cloned as", "originally cloned as a", "cloned as a gene", "as a gene highly", "a gene highly expressed", "gene highly expressed in", "highly expressed in white", "expressed in white blood", "in white blood cells", "blood cells duan", "cells duan et", "duan et al. 2004", "et al. 2004 .", "al. 2004 . several", "2004 . several studies", ". several studies suggest", "several studies suggest that", "suggest that notch2nl", "that notch2nl genes", "notch2nl genes may have", "genes may have played", "may have played a", "have played a role", "played a role in", "a role in the", "role in the evolutionary", "in the evolutionary expansion", "the evolutionary expansion of", "evolutionary expansion of the", "expansion of the human", "of the human brain", "human brain florio", "brain florio et", "florio et al. 2018", "al. 2018 fiddes", "2018 fiddes et", "fiddes et al. 2018", "al. 2018 suzuki", "2018 suzuki et", "suzuki et al. 2018", "al. 2018 lodewijk", "2018 lodewijk et", "lodewijk et al. 2020", "et al. 2020 .", "al. 2020 . notch2nl", "2020 . notch2nl genes", ". notch2nl genes are", "notch2nl genes are present", "genes are present only", "are present only in", "present only in the", "only in the hominidae", "in the hominidae family", "the hominidae family and", "family and while", "and while they", "while they are functional", "they are functional in", "are functional in humans", "in humans they", "humans they exist", "they exist as pseudogenes", "exist as pseudogenes in", "as pseudogenes in chimpanzees", "pseudogenes in chimpanzees and", "in chimpanzees and gorillas.", "chimpanzees and gorillas. in", "and gorillas. in addition", "in addition these", "addition these genes", "these genes are highly", "genes are highly expressed", "are highly expressed during", "highly expressed during brain", "expressed during brain development", "brain development florio", "development florio et", "al. 2018 and", "2018 and have", "and have the ability", "have the ability to", "the ability to delay", "ability to delay differentiation", "to delay differentiation of", "delay differentiation of neuronal", "differentiation of neuronal progenitors", "neuronal progenitors fiddes", "progenitors fiddes et", "et al. 2018 .", "al. 2018 . the", "2018 . the study", ". the study of", "the study of sequence", "study of sequence polymorphism", "of sequence polymorphism and", "sequence polymorphism and copy", "polymorphism and copy number", "and copy number variation", "copy number variation in", "number variation in notch2nl", "variation in notch2nl genes", "in notch2nl genes in", "notch2nl genes in modern", "genes in modern humans", "modern humans fiddes", "humans fiddes et", "2020 and", "and comparative analysis of", "comparative analysis of notch2nl", "analysis of notch2nl gene", "of notch2nl gene sequences", "notch2nl gene sequences between", "gene sequences between modern", "sequences between modern humans", "modern humans denisovans", "humans denisovans and", "and neanderthals lodewijk", "neanderthals lodewijk et", "2020 is", "is suggestive of an", "suggestive of an ongoing", "of an ongoing adaptive", "an ongoing adaptive evolution", "ongoing adaptive evolution of", "adaptive evolution of modern", "evolution of modern human", "of modern human notch2nl", "modern human notch2nl genes", "human notch2nl genes trending", "notch2nl genes trending toward", "genes trending toward lower", "trending toward lower levels", "toward lower levels of", "lower levels of notch2nl", "levels of notch2nl proteins.", "of notch2nl proteins. downstream", "notch2nl proteins. downstream of", "proteins. downstream of each", "downstream of each of", "of each of the", "each of the notch2nl", "of the notch2nl genes", "the notch2nl genes is", "notch2nl genes is an", "genes is an nbpf", "is an nbpf gene", "an nbpf gene in", "nbpf gene in the", "gene in the same", "in the same orientation", "the same orientation as", "same orientation as its", "orientation as its notch2nl", "as its notch2nl partner", "its notch2nl partner and", "notch2nl partner and co", "partner and co expressed", "and co expressed with", "co expressed with it", "with it nbpf10", "it nbpf10 downstream", "nbpf10 downstream of notch2nla", "of notch2nla nbpf14", "notch2nla nbpf14 downstream", "nbpf14 downstream of notch2nlb", "of notch2nlb nbpf19", "notch2nlb nbpf19 downstream", "nbpf19 downstream of notch2nlc", "of notch2nlc and", "notch2nlc and nbpf26", "and nbpf26 downstream of", "nbpf26 downstream of notch2nlr", "notch2nlr and", "and these notch2nl nbpf", "these notch2nl nbpf pairs", "notch2nl nbpf pairs likely", "nbpf pairs likely function", "pairs likely function in", "likely function in a", "function in a coordinated", "a coordinated complementary", "coordinated complementary fashion", "complementary fashion to promote", "fashion to promote neurogenesis", "to promote neurogenesis and", "promote neurogenesis and human", "neurogenesis and human brain", "and human brain expansion", "brain expansion fiddes", "expansion fiddes et", "fiddes et al. 2019", "et al. 2019 .

              the", "al. 2019 .

              the neurodevelopmental", "2019 .

              the neurodevelopmental disorder", ".

              the neurodevelopmental disorder known", "neurodevelopmental disorder known as", "disorder known as 1q21.1", "known as 1q21.1 distal", "as 1q21.1 distal deletion/duplication", "1q21.1 distal deletion/duplication syndrome", "distal deletion/duplication syndrome involves", "deletion/duplication syndrome involves copy", "syndrome involves copy number", "involves copy number gain", "copy number gain or", "number gain or loss", "gain or loss of", "or loss of the", "loss of the 1q21.1", "of the 1q21.1 chromosomal", "the 1q21.1 chromosomal region", "1q21.1 chromosomal region that", "chromosomal region that includes", "region that includes notch2nla", "that includes notch2nla and", "includes notch2nla and notch2nlb", "notch2nla and notch2nlb genes.", "and notch2nlb genes. copy", "notch2nlb genes. copy number", "genes. copy number loss", "copy number loss is", "number loss is associated", "loss is associated with", "is associated with microcephaly", "with microcephaly while", "microcephaly while copy", "while copy number gain", "copy number gain is", "number gain is associated", "gain is associated with", "is associated with macrocephaly", "with macrocephaly fiddes", "macrocephaly fiddes et", "and both gain and", "both gain and loss", "gain and loss are", "and loss are accompanied", "loss are accompanied with", "are accompanied with severe", "accompanied with severe neurological", "with severe neurological disorders", "neurological disorders fiddes", "disorders fiddes et", "al. 2020 . breakpoints", "2020 . breakpoints within", ". breakpoints within notch2nl", "breakpoints within notch2nl gene", "within notch2nl gene loci", "notch2nl gene loci are", "gene loci are also", "loci are also associated", "are also associated with", "also associated with neurological", "associated with neurological disorders", "neurological disorders lodewijk", "disorders lodewijk et", "et al. 2020 .

              expansion", "al. 2020 .

              expansion of", "2020 .

              expansion of the", ".

              expansion of the ggc", "of the ggc repeat", "the ggc repeat in", "ggc repeat in the", "repeat in the 5\u2019utr", "in the 5\u2019utr of", "the 5\u2019utr of the", "5\u2019utr of the notch2nlc", "of the notch2nlc gene", "the notch2nlc gene was", "notch2nlc gene was identified", "gene was identified as", "was identified as an", "identified as an important", "as an important contributor", "an important contributor to", "important contributor to neuronal", "contributor to neuronal intranuclear", "to neuronal intranuclear inclusion", "neuronal intranuclear inclusion disease", "inclusion disease niid", "niid and may", "and may play a", "may play a role", "play a role in", "a role in other", "role in other neurodegenerative", "in other neurodegenerative disorders", "other neurodegenerative disorders such", "neurodegenerative disorders such as", "disorders such as parkinson\u2019s", "such as parkinson\u2019s disease", "parkinson\u2019s disease alzheimer\u2019s", "disease alzheimer\u2019s disease", "alzheimer\u2019s disease frontotemporal", "disease frontotemporal dementia", "frontotemporal dementia ftd", "ftd and", "and amyotrophic lateral sclerosis", "lateral sclerosis als", "als to", "to name a few.", "name a few. the", "a few. the underlying", "few. the underlying pathogenic", "the underlying pathogenic mechanism", "underlying pathogenic mechanism has", "pathogenic mechanism has not", "mechanism has not been", "has not been elucidated.", "not been elucidated. for", "been elucidated. for review", "elucidated. for review of", "for review of notch2nlc", "review of notch2nlc related", "of notch2nlc related trinucleotide", "notch2nlc related trinucleotide expansion", "related trinucleotide expansion disorders", "expansion disorders please", "disorders please refer", "please refer to cao", "refer to cao et", "to cao et al.", "cao et al. 2021", "et al. 2021 and", "al. 2021 and huang", "2021 and huang et", "and huang et al.", "huang et al. 2021.", "

              the notch2nl gene family includes", "notch2nl gene family includes four", "gene family includes four genes", "includes four genes notch2nla", "genes notch2nla notch2nlb", "notch2nla notch2nlb notch2nlc", "notch2nlb notch2nlc and", "and notch2nlr which originated", "notch2nlr which originated from", "which originated from the partial", "originated from the partial duplication", "from the partial duplication of", "the partial duplication of the", "partial duplication of the first", "duplication of the first four", "of the first four exons", "the first four exons and", "first four exons and introns", "four exons and introns of", "exons and introns of the", "and introns of the notch2", "introns of the notch2 gene.", "of the notch2 gene. three", "the notch2 gene. three of", "notch2 gene. three of the", "gene. three of the duplicated", "three of the duplicated genes", "the duplicated genes notch2nla", "notch2nla notch2nlb and", "and notch2nlc reside at", "notch2nlc reside at the", "reside at the chromosomal band", "at the chromosomal band 1q21.1", "chromosomal band 1q21.1 while", "band 1q21.1 while notch2nlr", "1q21.1 while notch2nlr resides", "while notch2nlr resides at 1p12", "resides at 1p12 in", "at 1p12 in the", "1p12 in the vicinity", "in the vicinity of notch2.", "the vicinity of notch2. notch2nla", "vicinity of notch2. notch2nla was", "of notch2. notch2nla was originally", "notch2. notch2nla was originally cloned", "notch2nla was originally cloned as", "was originally cloned as a", "originally cloned as a gene", "cloned as a gene highly", "as a gene highly expressed", "a gene highly expressed in", "gene highly expressed in white", "highly expressed in white blood", "expressed in white blood cells", "white blood cells duan", "blood cells duan et", "cells duan et al.", "duan et al. 2004 .", "et al. 2004 . several", "al. 2004 . several studies", "2004 . several studies suggest", ". several studies suggest that", "studies suggest that notch2nl", "suggest that notch2nl genes", "that notch2nl genes may", "notch2nl genes may have played", "genes may have played a", "may have played a role", "have played a role in", "played a role in the", "a role in the evolutionary", "role in the evolutionary expansion", "in the evolutionary expansion of", "the evolutionary expansion of the", "evolutionary expansion of the human", "expansion of the human brain", "the human brain florio", "human brain florio et", "brain florio et al.", "et al. 2018 fiddes", "al. 2018 fiddes et", "2018 fiddes et al.", "et al. 2018 suzuki", "al. 2018 suzuki et", "2018 suzuki et al.", "et al. 2018 lodewijk", "al. 2018 lodewijk et", "2018 lodewijk et al.", "lodewijk et al. 2020 .", "et al. 2020 . notch2nl", "al. 2020 . notch2nl genes", "2020 . notch2nl genes are", ". notch2nl genes are present", "notch2nl genes are present only", "genes are present only in", "are present only in the", "present only in the hominidae", "only in the hominidae family", "in the hominidae family and", "hominidae family and while", "family and while they", "and while they are", "while they are functional in", "they are functional in humans", "functional in humans they", "in humans they exist", "humans they exist as", "they exist as pseudogenes in", "exist as pseudogenes in chimpanzees", "as pseudogenes in chimpanzees and", "pseudogenes in chimpanzees and gorillas.", "in chimpanzees and gorillas. in", "chimpanzees and gorillas. in addition", "gorillas. in addition these", "in addition these genes", "addition these genes are", "these genes are highly expressed", "genes are highly expressed during", "are highly expressed during brain", "highly expressed during brain development", "during brain development florio", "brain development florio et", "development florio et al.", "et al. 2018 and", "al. 2018 and have", "2018 and have the", "and have the ability to", "have the ability to delay", "the ability to delay differentiation", "ability to delay differentiation of", "to delay differentiation of neuronal", "delay differentiation of neuronal progenitors", "of neuronal progenitors fiddes", "neuronal progenitors fiddes et", "progenitors fiddes et al.", "suzuki et al. 2018 .", "et al. 2018 . the", "al. 2018 . the study", "2018 . the study of", ". the study of sequence", "the study of sequence polymorphism", "study of sequence polymorphism and", "of sequence polymorphism and copy", "sequence polymorphism and copy number", "polymorphism and copy number variation", "and copy number variation in", "copy number variation in notch2nl", "number variation in notch2nl genes", "variation in notch2nl genes in", "in notch2nl genes in modern", "notch2nl genes in modern humans", "in modern humans fiddes", "modern humans fiddes et", "humans fiddes et al.", "al. 2020 and", "2020 and comparative", "and comparative analysis of notch2nl", "comparative analysis of notch2nl gene", "analysis of notch2nl gene sequences", "of notch2nl gene sequences between", "notch2nl gene sequences between modern", "gene sequences between modern humans", "between modern humans denisovans", "modern humans denisovans and", "humans denisovans and neanderthals", "denisovans and neanderthals lodewijk", "and neanderthals lodewijk et", "neanderthals lodewijk et al.", "al. 2020 is", "2020 is suggestive", "is suggestive of an ongoing", "suggestive of an ongoing adaptive", "of an ongoing adaptive evolution", "an ongoing adaptive evolution of", "ongoing adaptive evolution of modern", "adaptive evolution of modern human", "evolution of modern human notch2nl", "of modern human notch2nl genes", "modern human notch2nl genes trending", "human notch2nl genes trending toward", "notch2nl genes trending toward lower", "genes trending toward lower levels", "trending toward lower levels of", "toward lower levels of notch2nl", "lower levels of notch2nl proteins.", "levels of notch2nl proteins. downstream", "of notch2nl proteins. downstream of", "notch2nl proteins. downstream of each", "proteins. downstream of each of", "downstream of each of the", "of each of the notch2nl", "each of the notch2nl genes", "of the notch2nl genes is", "the notch2nl genes is an", "notch2nl genes is an nbpf", "genes is an nbpf gene", "is an nbpf gene in", "an nbpf gene in the", "nbpf gene in the same", "gene in the same orientation", "in the same orientation as", "the same orientation as its", "same orientation as its notch2nl", "orientation as its notch2nl partner", "as its notch2nl partner and", "its notch2nl partner and co", "notch2nl partner and co expressed", "partner and co expressed with", "and co expressed with it", "expressed with it nbpf10", "with it nbpf10 downstream", "it nbpf10 downstream of", "downstream of notch2nla nbpf14", "of notch2nla nbpf14 downstream", "notch2nla nbpf14 downstream of", "downstream of notch2nlb nbpf19", "of notch2nlb nbpf19 downstream", "notch2nlb nbpf19 downstream of", "downstream of notch2nlc and", "of notch2nlc and nbpf26", "notch2nlc and nbpf26 downstream", "and nbpf26 downstream of notch2nlr", "of notch2nlr and", "notch2nlr and these", "and these notch2nl nbpf pairs", "these notch2nl nbpf pairs likely", "notch2nl nbpf pairs likely function", "nbpf pairs likely function in", "pairs likely function in a", "likely function in a coordinated", "in a coordinated complementary", "a coordinated complementary fashion", "coordinated complementary fashion to", "complementary fashion to promote neurogenesis", "fashion to promote neurogenesis and", "to promote neurogenesis and human", "promote neurogenesis and human brain", "neurogenesis and human brain expansion", "human brain expansion fiddes", "brain expansion fiddes et", "expansion fiddes et al.", "fiddes et al. 2019 .

              the", "et al. 2019 .

              the neurodevelopmental", "al. 2019 .

              the neurodevelopmental disorder", "2019 .

              the neurodevelopmental disorder known", ".

              the neurodevelopmental disorder known as", "neurodevelopmental disorder known as 1q21.1", "disorder known as 1q21.1 distal", "known as 1q21.1 distal deletion/duplication", "as 1q21.1 distal deletion/duplication syndrome", "1q21.1 distal deletion/duplication syndrome involves", "distal deletion/duplication syndrome involves copy", "deletion/duplication syndrome involves copy number", "syndrome involves copy number gain", "involves copy number gain or", "copy number gain or loss", "number gain or loss of", "gain or loss of the", "or loss of the 1q21.1", "loss of the 1q21.1 chromosomal", "of the 1q21.1 chromosomal region", "the 1q21.1 chromosomal region that", "1q21.1 chromosomal region that includes", "chromosomal region that includes notch2nla", "region that includes notch2nla and", "that includes notch2nla and notch2nlb", "includes notch2nla and notch2nlb genes.", "notch2nla and notch2nlb genes. copy", "and notch2nlb genes. copy number", "notch2nlb genes. copy number loss", "genes. copy number loss is", "copy number loss is associated", "number loss is associated with", "loss is associated with microcephaly", "associated with microcephaly while", "with microcephaly while copy", "microcephaly while copy number", "while copy number gain is", "copy number gain is associated", "number gain is associated with", "gain is associated with macrocephaly", "associated with macrocephaly fiddes", "with macrocephaly fiddes et", "macrocephaly fiddes et al.", "2018 and both", "and both gain and loss", "both gain and loss are", "gain and loss are accompanied", "and loss are accompanied with", "loss are accompanied with severe", "are accompanied with severe neurological", "accompanied with severe neurological disorders", "severe neurological disorders fiddes", "neurological disorders fiddes et", "disorders fiddes et al.", "et al. 2020 . breakpoints", "al. 2020 . breakpoints within", "2020 . breakpoints within notch2nl", ". breakpoints within notch2nl gene", "breakpoints within notch2nl gene loci", "within notch2nl gene loci are", "notch2nl gene loci are also", "gene loci are also associated", "loci are also associated with", "are also associated with neurological", "also associated with neurological disorders", "with neurological disorders lodewijk", "neurological disorders lodewijk et", "disorders lodewijk et al.", "lodewijk et al. 2020 .

              expansion", "et al. 2020 .

              expansion of", "al. 2020 .

              expansion of the", "2020 .

              expansion of the ggc", ".

              expansion of the ggc repeat", "of the ggc repeat in", "the ggc repeat in the", "ggc repeat in the 5\u2019utr", "repeat in the 5\u2019utr of", "in the 5\u2019utr of the", "the 5\u2019utr of the notch2nlc", "5\u2019utr of the notch2nlc gene", "of the notch2nlc gene was", "the notch2nlc gene was identified", "notch2nlc gene was identified as", "gene was identified as an", "was identified as an important", "identified as an important contributor", "as an important contributor to", "an important contributor to neuronal", "important contributor to neuronal intranuclear", "contributor to neuronal intranuclear inclusion", "to neuronal intranuclear inclusion disease", "intranuclear inclusion disease niid", "disease niid and", "niid and may play", "and may play a role", "may play a role in", "play a role in other", "a role in other neurodegenerative", "role in other neurodegenerative disorders", "in other neurodegenerative disorders such", "other neurodegenerative disorders such as", "neurodegenerative disorders such as parkinson\u2019s", "disorders such as parkinson\u2019s disease", "as parkinson\u2019s disease alzheimer\u2019s", "parkinson\u2019s disease alzheimer\u2019s disease", "alzheimer\u2019s disease frontotemporal dementia", "ftd and amyotrophic", "amyotrophic lateral sclerosis als", "als to name", "to name a few. the", "name a few. the underlying", "a few. the underlying pathogenic", "few. the underlying pathogenic mechanism", "the underlying pathogenic mechanism has", "underlying pathogenic mechanism has not", "pathogenic mechanism has not been", "mechanism has not been elucidated.", "has not been elucidated. for", "not been elucidated. for review", "been elucidated. for review of", "elucidated. for review of notch2nlc", "for review of notch2nlc related", "review of notch2nlc related trinucleotide", "of notch2nlc related trinucleotide expansion", "notch2nlc related trinucleotide expansion disorders", "trinucleotide expansion disorders please", "expansion disorders please refer", "disorders please refer to", "please refer to cao et", "refer to cao et al.", "to cao et al. 2021", "cao et al. 2021 and", "et al. 2021 and huang", "al. 2021 and huang et", "2021 and huang et al.", "and huang et al. 2021." ] }, { "record_id": "GLY_000594_1_2126", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9833109", "r hsa", "hsa 9833109", "r hsa 9833109" ] }, { "record_id": "GLY_000594_1_2126", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "evasion by", "by rsv", "rsv of", "of host", "host interferon", "interferon responses", "evasion by rsv", "by rsv of", "rsv of host", "of host interferon", "host interferon responses", "evasion by rsv of", "by rsv of host", "rsv of host interferon", "of host interferon responses", "evasion by rsv of host", "by rsv of host interferon", "rsv of host interferon responses", "infection with", "with human", "human 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with", "with mda5", "mda5 downregulating", "downregulating the", "the interferon", "interferon response", "response and", "and with", "with pkr", "blocking the", "the innate", "system signal", "signal for", "for shutting", "shutting down", "down protein", "protein translation.", "translation. further", "further interactions", "interactions of", "of the", "the m", "and g", "g proteins", "proteins are", "are reviewed", "by van", "van royen", "royen et", "et al", "infection with human", "with human respiratory", "human respiratory syncytial", "respiratory syncytial virus", "virus hrsv", "hrsv is", "is typically associated", "typically associated with", "associated with low", "with low to", "low to undetectable", "to undetectable levels", "undetectable levels of", "levels of type", "of type i", "type i interferons", "interferons ifns", "ifns . several", ". several hrsv", "several hrsv proteins", "hrsv proteins interact", "proteins interact with", "interact with host", "with host innate", 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"to undetectable levels of", "undetectable levels of type", "levels of type i", "of type i interferons", "i interferons ifns", "interferons ifns .", "ifns . several hrsv", ". several hrsv proteins", "several hrsv proteins interact", "hrsv proteins interact with", "proteins interact with host", "interact with host innate", "with host innate immune", "host innate immune system", "innate immune system factors", "immune system factors that", "system factors that support", "factors that support the", "that support the type", "support the type i", "the type i interferon", "type i interferon response.", "i interferon response. nonstructural", "interferon response. nonstructural proteins", "response. nonstructural proteins ns1", "nonstructural proteins ns1 and", "proteins ns1 and ns2", "ns1 and ns2 localize", "and ns2 localize to", "ns2 localize to mitochondria", "localize to mitochondria and", "to mitochondria and nucleus", "mitochondria and nucleus where", "and nucleus where they", "nucleus where they bind", "where they bind mavs", "bind mavs ddx58", "irf3 and crebbp", "and crebbp affecting", "crebbp affecting ddx58/ifih1", "affecting ddx58/ifih1 mediated interferon", "ddx58/ifih1 mediated interferon induction", "interferon induction reviewed", "induction reviewed by", "reviewed by thornhill &", "by thornhill & verhoeven", "& verhoeven 2020", "verhoeven 2020 .", ". additionally hrsv", "additionally hrsv nucleoprotein", "hrsv nucleoprotein interacts with", "nucleoprotein interacts with mda5", "interacts with mda5 downregulating", "with mda5 downregulating the", "mda5 downregulating the interferon", "downregulating the interferon response", "the interferon response and", "interferon response and with", "response and with pkr", "with pkr eif2ak2", "eif2ak2 blocking the", "blocking the innate immune", "the innate immune system", "innate immune system signal", "immune system signal for", "system signal for shutting", "signal for shutting down", "for shutting down protein", "shutting down protein translation.", "down protein translation. further", "protein translation. further interactions", "translation. further interactions of", "further interactions of the", "interactions of the m", "the m sh", "sh and g", "and g proteins are", "g proteins are reviewed", "proteins are reviewed by", "are reviewed by van", "reviewed by van royen", "by van royen et", "van royen et al", "et al 2022.", "infection with human respiratory syncytial", "with human respiratory syncytial virus", "respiratory syncytial virus hrsv", "virus hrsv is", "hrsv is typically associated", "is typically associated with low", "typically associated with low to", "associated with low to undetectable", "with low to undetectable levels", "low to undetectable levels of", "to undetectable levels of type", "undetectable levels of type i", "levels of type i interferons", "type i interferons ifns", "i interferons ifns .", "interferons ifns . several", "ifns . several hrsv proteins", ". several hrsv proteins interact", "several hrsv proteins interact with", "hrsv proteins interact with host", "proteins interact with host innate", "interact with host innate immune", "with host innate immune system", "host innate immune system factors", "innate immune system factors that", "immune system factors that support", "system factors that support the", "factors that support the type", "that support the type i", "support the type i interferon", "the type i interferon response.", "type i interferon response. nonstructural", "i interferon response. nonstructural proteins", "interferon response. nonstructural proteins ns1", "response. nonstructural proteins ns1 and", "nonstructural proteins ns1 and ns2", "proteins ns1 and ns2 localize", "ns1 and ns2 localize to", "and ns2 localize to mitochondria", "ns2 localize to mitochondria and", "localize to mitochondria and nucleus", "to mitochondria and nucleus where", "mitochondria and nucleus where they", "and nucleus where they bind", "nucleus where they bind mavs", "they bind mavs ddx58", "mavs ddx58 trim25", "ddx58 trim25 irf3", "trim25 irf3 and", "and crebbp affecting ddx58/ifih1", "crebbp affecting ddx58/ifih1 mediated", "affecting ddx58/ifih1 mediated interferon induction", "mediated interferon induction reviewed", "interferon induction reviewed by", "induction reviewed by thornhill", "reviewed by thornhill & verhoeven", "thornhill & verhoeven 2020", "& verhoeven 2020 .", "verhoeven 2020 . additionally", "2020 . additionally hrsv", ". additionally hrsv nucleoprotein", "additionally hrsv nucleoprotein interacts", "hrsv nucleoprotein interacts with mda5", "nucleoprotein interacts with mda5 downregulating", "interacts with mda5 downregulating the", "with mda5 downregulating the interferon", "mda5 downregulating the interferon response", "downregulating the interferon response and", "the interferon response and with", "interferon response and with pkr", "and with pkr eif2ak2", "pkr eif2ak2 blocking", "eif2ak2 blocking the innate", "blocking the innate immune system", "the innate immune system signal", "innate immune system signal for", "immune system signal for shutting", "system signal for shutting down", "signal for shutting down protein", "for shutting down protein translation.", "shutting down protein translation. further", "down protein translation. further interactions", "protein translation. further interactions of", "translation. further interactions of the", "further interactions of the m", "of the m sh", "m sh and", "sh and g proteins", "and g proteins are reviewed", "g proteins are reviewed by", "proteins are reviewed by van", "are reviewed by van royen", "reviewed by van royen et", "by van royen et al", "royen et al 2022." ] }, { "record_id": "GLY_000594_1_2127", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9725554", "r hsa", "hsa 9725554", "r hsa 9725554" ] }, { "record_id": "GLY_000594_1_2127", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "differentiation of", "of keratinocytes", "keratinocytes in", "in interfollicular", "interfollicular epidermis", "epidermis in", "in mammalian", "mammalian skin", "differentiation of keratinocytes", "of keratinocytes in", "keratinocytes in interfollicular", "in interfollicular epidermis", "interfollicular epidermis in", "epidermis in mammalian", "in mammalian skin", "differentiation of keratinocytes in", "of keratinocytes in interfollicular", "keratinocytes in interfollicular epidermis", "in interfollicular epidermis in", "interfollicular epidermis in mammalian", "epidermis in mammalian skin", "differentiation of keratinocytes in interfollicular", "of keratinocytes in interfollicular epidermis", "keratinocytes in interfollicular epidermis in", "in interfollicular epidermis in mammalian", "interfollicular epidermis in mammalian skin", "the interfollicular", "epidermis is", "is the", "the skin", "skin surface", "surface layer", "layer in", "in between", "between the", "the adnexa", "hair follicles", "sweat glands", "and sebaceous", "sebaceous glands", "glands .", ". going", "going from", "from the", "the dermal", "dermal epidermal", "epidermal junction", "epidermis strata", "strata include", "include the", "the basal", "basal layer", "stratum basale", "spinous layer", "stratum spinosum", "granular layer", "stratum granulosum", "and the", "the cornified", "cornified layer", "stratum corneum", "corneum .", ". the", "layer consists", "consists of", "of keratinocyte", "keratinocyte stem", "stem cells", "cells and", "and transit", "transit amplifying", "amplifying cells.", "cells. the", "the spinous", "and cornified", "cornified layers", "layers consist", "consist of", "of spinous", "spinous keratinocytes", "granular keratinocytes", "and corneocytes", "respectively. interfollicular", "epidermis has", "has a", "a high", "high cell", "cell turnover", "turnover rate.", "rate. keratinocyte", "cells self", "self renew", "renew throughout", "throughout adulthood", "adulthood and", "and give", "give rise", "rise to", "to transit", "cells. transit", "amplifying cells", "cells undergo", "undergo several", "several cell", "cell cycles", "cycles before", "before committing", "committing to", "to differentiation", "first into", "into spinous", "layer keratinocytes", "then into", "into granular", "and finally", "finally into", "into corneocytes.", "corneocytes. corneocytes", "corneocytes lose", "lose their", "their nuclei", "nuclei and", "and cytoplasmic", "cytoplasmic organelles", "forming flattened", "flattened squames", "squames that", "that provide", "provide a", "a physical", "physical barrier", "barrier against", "against the", "the invasion", "invasion of", "of pathogens", "pathogens and", "and loss", "loss of", "of bodily", "bodily fluids.", "fluids. for", "for a", "a detailed", "detailed review", "please refer", "refer to", "to zijl", "zijl et", "et al.", "al. 2022", "and for", "for the", "the single", "single cell", "cell transcriptomic", "transcriptomic and", "and spatial", "spatial transcriptomic", "transcriptomic studies", "studies that", "a higher", "higher resolution", "resolution view", "view of", "of human", "human interfollicular", "to cheng", "cheng et", "al. 2018", "wang et", "al. 2020", "aragona et", "haensel et", "negri et", "al. 2023", "and ganier", "ganier et", "al. 2024", "2024 .

              the", ".

              the cell", "cell lineage", "lineage path", "path of", "is depicted", "depicted through", "through four", "four cell", "cell differentiation", "differentiation steps", "steps involving", "involving five", "five distinct", "distinct cellular", "cellular states:", "states: keratinocyte", "cells of", "of epidermal", "epidermal basal", "and corneocytes.", "corneocytes. each", "each differentiation", "differentiation step", "step is", "is regulated", "regulated by", "by a", "a distinct", "distinct combination", "combination of", "of regulatory", "regulatory molecules", "molecules present", "present in", "in the", "the microenvironment", "microenvironment of", "of differentiating", "differentiating cells.", "the interfollicular epidermis", "interfollicular epidermis is", "epidermis is the", "is the skin", "the skin surface", "skin surface layer", "surface layer in", "layer in between", "in between the", "between the adnexa", "adnexa hair", "follicles sweat", "glands and", "and sebaceous glands", "sebaceous glands .", "glands . going", ". going from", "going from the", "from the dermal", "the dermal epidermal", "dermal epidermal junction", "junction the", "interfollicular epidermis strata", "epidermis strata include", "strata include the", "include the basal", "the basal layer", "layer stratum", "and the cornified", "the cornified layer", "stratum corneum .", "corneum . the", ". the basal", "basal layer consists", "layer consists of", "consists of keratinocyte", "of keratinocyte stem", "keratinocyte stem cells", "stem cells and", "cells and transit", "and transit amplifying", "transit amplifying cells.", "amplifying cells. the", "cells. the spinous", "spinous granular", "granular and", "and cornified layers", "cornified layers consist", "layers consist of", "consist of spinous", "of spinous keratinocytes", "keratinocytes granular", "keratinocytes and", "corneocytes respectively.", "respectively. interfollicular epidermis", "interfollicular epidermis has", "epidermis has a", "has a high", "a high cell", "high cell turnover", "cell turnover rate.", "turnover rate. keratinocyte", "rate. keratinocyte stem", "stem cells self", "cells self renew", "self renew throughout", "renew throughout adulthood", "throughout adulthood and", "adulthood and give", "and give rise", "give rise to", "rise to transit", "to transit amplifying", "amplifying cells. transit", "cells. transit amplifying", "transit amplifying cells", "amplifying cells undergo", "cells undergo several", "undergo several cell", "several cell cycles", "cell cycles before", "cycles before committing", "before committing to", "committing to differentiation", "differentiation first", "first into spinous", "into spinous layer", "spinous layer keratinocytes", "keratinocytes then", "then into granular", "into granular layer", "granular layer keratinocytes", "and finally into", "finally into corneocytes.", "into corneocytes. corneocytes", "corneocytes. corneocytes lose", "corneocytes lose their", "lose their nuclei", "their nuclei and", "nuclei and cytoplasmic", "and cytoplasmic organelles", "organelles forming", "forming flattened squames", "flattened squames that", "squames that provide", "that provide a", "provide a physical", "a physical barrier", "physical barrier against", "barrier against the", "against the invasion", "the invasion of", "invasion of pathogens", "of pathogens and", "pathogens and loss", "and loss of", "loss of bodily", "of bodily fluids.", "bodily fluids. for", "fluids. for a", "for a detailed", "a detailed review", "review please", "please refer to", "refer to zijl", "to zijl et", "zijl et al.", "et al. 2022", "2022 and", "and for the", "for the single", "the single cell", "single cell transcriptomic", "cell transcriptomic and", "transcriptomic and spatial", "and spatial transcriptomic", "spatial transcriptomic studies", "transcriptomic studies that", "studies that provide", "provide a higher", "a higher resolution", "higher resolution view", "resolution view of", "view of human", "of human interfollicular", "human interfollicular epidermis", "epidermis please", "refer to cheng", "to cheng et", "cheng et al.", "et al. 2018", "2018 wang", "wang et al.", "et al. 2020", "2020 aragona", "aragona et al.", "2020 haensel", "haensel et al.", "2020 negri", "negri et al.", "et al. 2023", "2023 and", "and ganier et", "ganier et al.", "et al. 2024", "al. 2024 .

              the", "2024 .

              the cell", ".

              the cell lineage", "cell lineage path", "lineage path of", "path of keratinocytes", "epidermis is depicted", "is depicted through", "depicted through four", "through four cell", "four cell differentiation", "cell differentiation steps", "differentiation steps involving", "steps involving five", "involving five distinct", "five distinct cellular", "distinct cellular states:", "cellular states: keratinocyte", "states: keratinocyte stem", "stem cells of", "cells of epidermal", "of epidermal basal", "epidermal basal layer", "layer transit", "cells spinous", "and corneocytes. each", "corneocytes. each differentiation", "each differentiation step", "differentiation step is", "step is regulated", "is regulated by", "regulated by a", "by a distinct", "a distinct combination", "distinct combination of", "combination of regulatory", "of regulatory molecules", "regulatory molecules present", "molecules present in", "present in the", "in the microenvironment", "the microenvironment of", "microenvironment of differentiating", "of differentiating cells.", "the interfollicular epidermis is", "interfollicular epidermis is the", "epidermis is the skin", "is the skin surface", "the skin surface layer", "skin surface layer in", "surface layer in between", "layer in between the", "in between the adnexa", "the adnexa hair", "adnexa hair follicles", "hair follicles sweat", "follicles sweat glands", "sweat glands and", "glands and sebaceous", "and sebaceous glands .", "sebaceous glands . going", "glands . going from", ". going from the", "going from the dermal", "from the dermal epidermal", "the dermal epidermal junction", "epidermal junction the", "junction the interfollicular", "the interfollicular epidermis strata", "interfollicular epidermis strata include", "epidermis strata include the", "strata include the basal", "include the basal layer", "basal layer stratum", "layer stratum basale", "basale spinous", "spinous layer stratum", "layer stratum spinosum", "spinosum granular", "granular layer stratum", "layer stratum granulosum", "granulosum and", "and the cornified layer", "cornified layer stratum", "layer stratum corneum", "stratum corneum . the", "corneum . the basal", ". the basal layer", "the basal layer consists", "basal layer consists of", "layer consists of keratinocyte", "consists of keratinocyte stem", "of keratinocyte stem cells", "keratinocyte stem cells and", "stem cells and transit", "cells and transit amplifying", "and transit amplifying cells.", "transit amplifying cells. the", "amplifying cells. the spinous", "the spinous granular", "granular and cornified", "and cornified layers consist", "cornified layers consist of", "layers consist of spinous", "consist of spinous keratinocytes", "spinous keratinocytes granular", "keratinocytes granular keratinocytes", "granular keratinocytes and", "keratinocytes and corneocytes", "and corneocytes respectively.", "corneocytes respectively. interfollicular", "respectively. interfollicular epidermis has", "interfollicular epidermis has a", "epidermis has a high", "has a high cell", "a high cell turnover", "high cell turnover rate.", "cell turnover rate. keratinocyte", "turnover rate. keratinocyte stem", "rate. keratinocyte stem cells", "keratinocyte stem cells self", "stem cells self renew", "cells self renew throughout", "self renew throughout adulthood", "renew throughout adulthood and", "throughout adulthood and give", "adulthood and give rise", "and give rise to", "give rise to transit", "rise to transit amplifying", "to transit amplifying cells.", "transit amplifying cells. transit", "amplifying cells. transit amplifying", "cells. transit amplifying cells", "transit amplifying cells undergo", "amplifying cells undergo several", "cells undergo several cell", "undergo several cell cycles", "several cell cycles before", "cell cycles before committing", "cycles before committing to", "before committing to differentiation", "to differentiation first", "differentiation first into", "first into spinous layer", "into spinous layer keratinocytes", "layer keratinocytes then", "keratinocytes then into", "then into granular layer", "into granular layer keratinocytes", "layer keratinocytes and", "keratinocytes and finally", "and finally into corneocytes.", "finally into corneocytes. corneocytes", "into corneocytes. corneocytes lose", "corneocytes. corneocytes lose their", "corneocytes lose their nuclei", "lose their nuclei and", "their nuclei and cytoplasmic", "nuclei and cytoplasmic organelles", "cytoplasmic organelles forming", "organelles forming flattened", "forming flattened squames that", "flattened squames that provide", "squames that provide a", "that provide a physical", "provide a physical barrier", "a physical barrier against", "physical barrier against the", "barrier against the invasion", "against the invasion of", "the invasion of pathogens", "invasion of pathogens and", "of pathogens and loss", "pathogens and loss of", "and loss of bodily", "loss of bodily fluids.", "of bodily fluids. for", "bodily fluids. for a", "fluids. for a detailed", "for a detailed review", "detailed review please", "review please refer", "please refer to zijl", "refer to zijl et", "to zijl et al.", "zijl et al. 2022", "al. 2022 and", "2022 and for", "and for the single", "for the single cell", "the single cell transcriptomic", "single cell transcriptomic and", "cell transcriptomic and spatial", "transcriptomic and spatial transcriptomic", "and spatial transcriptomic studies", "spatial transcriptomic studies that", "transcriptomic studies that provide", "studies that provide a", "that provide a higher", "provide a higher resolution", "a higher resolution view", "higher resolution view of", "resolution view of human", "view of human interfollicular", "of human interfollicular epidermis", "interfollicular epidermis please", "epidermis please refer", "please refer to cheng", "refer to cheng et", "to cheng et al.", "cheng et al. 2018", "al. 2018 wang", "2018 wang et", "wang et al. 2020", "al. 2020 aragona", "2020 aragona et", "aragona et al. 2020", "al. 2020 haensel", "2020 haensel et", "haensel et al. 2020", "al. 2020 negri", "2020 negri et", "negri et al. 2023", "al. 2023 and", "2023 and ganier", "and ganier et al.", "ganier et al. 2024", "et al. 2024 .

              the", "al. 2024 .

              the cell", "2024 .

              the cell lineage", ".

              the cell lineage path", "cell lineage path of", "lineage path of keratinocytes", "path of keratinocytes in", "in interfollicular epidermis is", "interfollicular epidermis is depicted", "epidermis is depicted through", "is depicted through four", "depicted through four cell", "through four cell differentiation", "four cell differentiation steps", "cell differentiation steps involving", "differentiation steps involving five", "steps involving five distinct", "involving five distinct cellular", "five distinct cellular states:", "distinct cellular states: keratinocyte", "cellular states: keratinocyte stem", "states: keratinocyte stem cells", "keratinocyte stem cells of", "stem cells of epidermal", "cells of epidermal basal", "of epidermal basal layer", "basal layer transit", "layer transit amplifying", "amplifying cells spinous", "cells spinous keratinocytes", "keratinocytes and corneocytes.", "and corneocytes. each differentiation", "corneocytes. each differentiation step", "each differentiation step is", "differentiation step is regulated", "step is regulated by", "is regulated by a", "regulated by a distinct", "by a distinct combination", "a distinct combination of", "distinct combination of regulatory", "combination of regulatory molecules", "of regulatory molecules present", "regulatory molecules present in", "molecules present in the", "present in the microenvironment", "in the microenvironment of", "the microenvironment of differentiating", "microenvironment of differentiating cells.", "the interfollicular epidermis is the", "interfollicular epidermis is the skin", "epidermis is the skin surface", "is the skin surface layer", "the skin surface layer in", "skin surface layer in between", "surface layer in between the", "layer in between the adnexa", "between the adnexa hair", "the adnexa hair follicles", "hair follicles sweat glands", "sweat glands and sebaceous", "glands and sebaceous glands", "and sebaceous glands . going", "sebaceous glands . going from", "glands . going from the", ". going from the dermal", "going from the dermal epidermal", "from the dermal epidermal junction", "dermal epidermal junction the", "epidermal junction the interfollicular", "junction the interfollicular epidermis", "the interfollicular epidermis strata include", "interfollicular epidermis strata include the", "epidermis strata include the basal", "strata include the basal layer", "the basal layer stratum", "basal layer stratum basale", "stratum basale spinous", "basale spinous layer", "spinous layer stratum spinosum", "stratum spinosum granular", "spinosum granular layer", "granular layer stratum granulosum", "stratum granulosum and", "granulosum and the", "the cornified layer stratum", "cornified layer stratum corneum", "layer stratum corneum .", "stratum corneum . the basal", "corneum . the basal layer", ". the basal layer consists", "the basal layer consists of", "basal layer consists of keratinocyte", "layer consists of keratinocyte stem", "consists of keratinocyte stem cells", "of keratinocyte stem cells and", "keratinocyte stem cells and transit", "stem cells and transit amplifying", "cells and transit amplifying cells.", "and transit amplifying cells. the", "transit amplifying cells. the spinous", "cells. the spinous granular", "spinous granular and", "granular and cornified layers", "and cornified layers consist of", "cornified layers consist of spinous", "layers consist of spinous keratinocytes", "of spinous keratinocytes granular", "spinous keratinocytes granular keratinocytes", "granular keratinocytes and corneocytes", "and corneocytes respectively. interfollicular", "corneocytes respectively. interfollicular epidermis", "respectively. interfollicular epidermis has a", "interfollicular epidermis has a high", "epidermis has a high cell", "has a high cell turnover", "a high cell turnover rate.", "high cell turnover rate. keratinocyte", "cell turnover rate. keratinocyte stem", "turnover rate. keratinocyte stem cells", "rate. keratinocyte stem cells self", "keratinocyte stem cells self renew", "stem cells self renew throughout", "cells self renew throughout adulthood", "self renew throughout adulthood and", "renew throughout adulthood and give", "throughout adulthood and give rise", "adulthood and give rise to", "and give rise to transit", "give rise to transit amplifying", "rise to transit amplifying cells.", "to transit amplifying cells. transit", "transit amplifying cells. transit amplifying", "amplifying cells. transit amplifying cells", "cells. transit amplifying cells undergo", "transit amplifying cells undergo several", "amplifying cells undergo several cell", "cells undergo several cell cycles", "undergo several cell cycles before", "several cell cycles before committing", "cell cycles before committing to", "cycles before committing to differentiation", "committing to differentiation first", "to differentiation first into", "differentiation first into spinous", "first into spinous layer keratinocytes", "spinous layer keratinocytes then", "layer keratinocytes then into", "keratinocytes then into granular", "then into granular layer keratinocytes", "granular layer keratinocytes and", "layer keratinocytes and finally", "keratinocytes and finally into", "and finally into corneocytes. corneocytes", "finally into corneocytes. corneocytes lose", "into corneocytes. corneocytes lose their", "corneocytes. corneocytes lose their nuclei", "corneocytes lose their nuclei and", "lose their nuclei and cytoplasmic", "their nuclei and cytoplasmic organelles", "and cytoplasmic organelles forming", "cytoplasmic organelles forming flattened", "organelles forming flattened squames", "forming flattened squames that provide", "flattened squames that provide a", "squames that provide a physical", "that provide a physical barrier", "provide a physical barrier against", "a physical barrier against the", "physical barrier against the invasion", "barrier against the invasion of", "against the invasion of pathogens", "the invasion of pathogens and", "invasion of pathogens and loss", "of pathogens and loss of", "pathogens and loss of bodily", "and loss of bodily fluids.", "loss of bodily fluids. for", "of bodily fluids. for a", "bodily fluids. for a detailed", "fluids. for a detailed review", "a detailed review please", "detailed review please refer", "review please refer to", "please refer to zijl et", "refer to zijl et al.", "to zijl et al. 2022", "et al. 2022 and", "al. 2022 and for", "2022 and for the", "and for the single cell", "for the single cell transcriptomic", "the single cell transcriptomic and", "single cell transcriptomic and spatial", "cell transcriptomic and spatial transcriptomic", "transcriptomic and spatial transcriptomic studies", "and spatial transcriptomic studies that", "spatial transcriptomic studies that provide", "transcriptomic studies that provide a", "studies that provide a higher", "that provide a higher resolution", "provide a higher resolution view", "a higher resolution view of", "higher resolution view of human", "resolution view of human interfollicular", "view of human interfollicular epidermis", "human interfollicular epidermis please", "interfollicular epidermis please refer", "epidermis please refer to", "please refer to cheng et", "refer to cheng et al.", "to cheng et al. 2018", "et al. 2018 wang", "al. 2018 wang et", "2018 wang et al.", "et al. 2020 aragona", "al. 2020 aragona et", "2020 aragona et al.", "et al. 2020 haensel", "al. 2020 haensel et", "2020 haensel et al.", "et al. 2020 negri", "al. 2020 negri et", "2020 negri et al.", "et al. 2023 and", "al. 2023 and ganier", "2023 and ganier et", "and ganier et al. 2024", "ganier et al. 2024 .

              the", "et al. 2024 .

              the cell", "al. 2024 .

              the cell lineage", "2024 .

              the cell lineage path", ".

              the cell lineage path of", "cell lineage path of keratinocytes", "lineage path of keratinocytes in", "path of keratinocytes in interfollicular", "keratinocytes in interfollicular epidermis is", "in interfollicular epidermis is depicted", "interfollicular epidermis is depicted through", "epidermis is depicted through four", "is depicted through four cell", "depicted through four cell differentiation", "through four cell differentiation steps", "four cell differentiation steps involving", "cell differentiation steps involving five", "differentiation steps involving five distinct", "steps involving five distinct cellular", "involving five distinct cellular states:", "five distinct cellular states: keratinocyte", "distinct cellular states: keratinocyte stem", "cellular states: keratinocyte stem cells", "states: keratinocyte stem cells of", "keratinocyte stem cells of epidermal", "stem cells of epidermal basal", "cells of epidermal basal layer", "epidermal basal layer transit", "basal layer transit amplifying", "layer transit amplifying cells", "transit amplifying cells spinous", "amplifying cells spinous keratinocytes", "granular keratinocytes and corneocytes.", "keratinocytes and corneocytes. each", "and corneocytes. each differentiation step", "corneocytes. each differentiation step is", "each differentiation step is regulated", "differentiation step is regulated by", "step is regulated by a", "is regulated by a distinct", "regulated by a distinct combination", "by a distinct combination of", "a distinct combination of regulatory", "distinct combination of regulatory molecules", "combination of regulatory molecules present", "of regulatory molecules present in", "regulatory molecules present in the", "molecules present in the microenvironment", "present in the microenvironment of", "in the microenvironment of differentiating", "the microenvironment of differentiating cells." ] }, { "record_id": "GLY_000594_1_2128", "filename": 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              relief", "
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              in", ".
              in addition", "addition to", "to transcriptional", "transcriptional regulation", "m activity", "activity is", "is also", "also controlled", "controlled by", "by post", "translational modifications", "although the", "the significance", "significance of", "of these", "these modifications", "modifications is", "is not", "not always", "always clear.", "clear. sumoylation", "ubiquitination and", "and phosphorylation", "phosphorylation downstream", "downstream of", "of mapk", "wnt and", "and akt", "akt signaling", "signaling can", "can all", "all impact", "impact the", "the stability", "localization or", "or activity", "in goding", "and acetylation", "acetylation regulates", "regulates the", "the occupancy", "occupancy of", "of target", "target promoters", "decreasing occupancy", "occupancy at", "at differentiation", "differentiation specific", "specific promoters", "louphrasitthiphol et", "2023 .", ".
              ", "melanocytes neurons", "neurons and glia", "and glia all", "glia all arise", "all arise from", "arise from precursor", "from precursor cells", "precursor cells derived", "cells derived from", "derived from neural", "from neural crest", "neural crest cells.", "crest cells. cells", "cells. cells that", "cells that will", "that will give", "will give rise", "give rise to", "rise to neurons", "to neurons and", "and glia migrate", "glia migrate away", "migrate away from", "away from the", "from the neural", "the neural crest", "neural crest earlier", "crest earlier and", "earlier and in", "and in a", "in a ventral", "a ventral pattern", "pattern while", "while cells that", "rise to melanocytes", "to melanocytes leave", "melanocytes leave the", "leave the neural", "neural crest later", "crest later and", "later and migrate", "and migrate dorsolaterally.", "migrate dorsolaterally. nevertheless", "nevertheless melanocytes", "melanocytes can also", "can also arise", "also arise in", "arise in an", "in an alternate", "an alternate pathway", "alternate pathway from", "pathway from dual", "from dual schwann", "dual schwann cell/melanocyte", "schwann cell/melanocyte precursors", "cell/melanocyte precursors or", "precursors or by", "or by dedifferentiation", "by dedifferentiation from", "dedifferentiation from schwann", "from schwann cells", "cells a", "a derivative of", "derivative of the", "of the glial", "the glial lineage", "lineage reviewed", "reviewed in mort", "in mort et", "mort et al", "al 2015", "2015 . mitf", ". mitf m", "mitf m is", "m is a", "is a key", "a key regulator", "key regulator of", "regulator of melanocyte", "of melanocyte development", "development and", "and its expression", "its expression distinguishes", "expression distinguishes the", "distinguishes the melanocyte", "the melanocyte fate", "melanocyte fate from", "fate from that", "from that of", "that of glial", "of glial and", "glial and neural", "and neural cells.", "neural cells. mitf", "cells. mitf m", "m expression is", "expression is repressed", "is repressed in", "repressed in precursors", "in precursors through", "precursors through the", "through the activity", "the activity of", "activity of foxd3", "of foxd3 and", "foxd3 and sox2.", "and sox2. depending", "sox2. depending on", "depending on the", "on the species", "species these", "these transcription factors", "transcription factors may", "factors may either", "may either bind", "either bind directly", "bind directly to", "directly to elements", "to elements in", "elements in the", "in the mitf", "the mitf m", "mitf m promoter", "m promoter to", "promoter to repress", "to repress transcription", "transcription or", "or may act", "may act independently", "act independently of", "independently of dna", "of dna binding", "dna binding by", "binding by disrupting", "by disrupting protein", "disrupting protein protein", "protein protein interactions", "protein interactions that", "interactions that promote", "that promote transcriptional", "promote transcriptional activity", "activity nitzan", "nitzan et al", "al 2013a", "b curran", "curran et al", "al 2009", "2009 2010", "2010 adameyko", "adameyko et al", "al 2012", "2012 reviewed", "2015 white", "white and zon", "zon 2008", "2008 goding", "goding and arnheiter", "arnheiter 2019", "2019 . foxd3", ". foxd3 and", "foxd3 and sox2", "and sox2 expression", "turn are", "are regulated by", "regulated by a", "by a cascade", "a cascade of", "cascade of other", "of other transcription", "other transcription factors", "factors including", "zic1 pax3", "pax3 snail2", "snail2 and sox9", "sox9 reviewed", "2015 goding", "2019 .
              relief", ".
              relief of", "
              relief of foxd3", "of foxd3 mediated", "foxd3 mediated repression", "mediated repression may", "repression may depend", "may depend in", "depend in part", "in part on", "part on hdac1", "hdac1 as", "as well as", "well as on", "as on down", "on down regulation", "down regulation of", "regulation of snail2", "snail2 ignatius", "ignatius et al", "al 2008", "2008 greenhill", "greenhill et al", "al 2011", "2011 nitzan", "b . mitf", "m expression in", "expression in unpigmented", "in unpigmented but", "unpigmented but committed", "but committed melanoblasts", "committed melanoblasts depends", "melanoblasts depends on", "depends on pax3", "on pax3 and", "pax3 and sox10", "and sox10 binding", "sox10 binding at", "binding at the", "at the promoter", "the promoter as", "promoter as well", "as on wnt", "wnt ednrb", "ednrb and kit", "and kit signaling", "signaling reviewed", "2019 . initial", ". initial expression", "initial expression of", "expression of mitf", "mitf m also", "m also contributes", "also contributes to", "contributes to downregulation", "to downregulation of", "downregulation of foxd3", "and sox2 establishing", "sox2 establishing a", "establishing a positive", "a positive feedback", "positive feedback loop", "feedback loop that", "loop that reinforces", "that reinforces commitment", "reinforces commitment to", "commitment to the", "to the melanocyte", "fate reviewed", "2019 .
              in addition", ".
              in addition to", "addition to transcriptional", "to transcriptional regulation", "regulation mitf", "mitf m activity", "m activity is", "activity is also", "is also controlled", "also controlled by", "controlled by post", "by post translational", "post translational modifications", "modifications although", "although the significance", "the significance of", "significance of these", "of these modifications", "these modifications is", "modifications is not", "is not always", "not always clear.", "always clear. sumoylation", "sumoylation ubiquitination", "ubiquitination and phosphorylation", "and phosphorylation downstream", "phosphorylation downstream of", "downstream of mapk", "mapk wnt", "wnt and akt", "and akt signaling", "akt signaling can", "signaling can all", "can all impact", "all impact the", "impact the stability", "stability localization", "localization or activity", "or activity of", "activity of mitf", "m reviewed", "reviewed in goding", "in goding and", "and acetylation regulates", "acetylation regulates the", "regulates the occupancy", "the occupancy of", "occupancy of target", "of target promoters", "promoters decreasing", "decreasing occupancy at", "occupancy at differentiation", "at differentiation specific", "differentiation specific promoters", "promoters louphrasitthiphol", "louphrasitthiphol et al", "al 2020", "2020 2023", "2023 .
              ", "melanocytes neurons and", "neurons and glia all", "and glia all arise", "glia all arise from", "all arise from precursor", "arise from precursor cells", "from precursor cells derived", "precursor cells derived from", "cells derived from neural", "derived from neural crest", "from neural crest cells.", "neural crest cells. cells", "crest cells. cells that", "cells. cells that will", "cells that will give", "that will give rise", "will give rise to", "give rise to neurons", "rise to neurons and", "to neurons and glia", "neurons and glia migrate", "and glia migrate away", "glia migrate away from", "migrate away from the", "away from the neural", "from the neural crest", "the neural crest earlier", "neural crest earlier and", "crest earlier and in", "earlier and in a", "and in a ventral", "in a ventral pattern", "ventral pattern while", "pattern while cells", "while cells that will", "give rise to melanocytes", "rise to melanocytes leave", "to melanocytes leave the", "melanocytes leave the neural", "leave the neural crest", "the neural crest later", "neural crest later and", "crest later and migrate", "later and migrate dorsolaterally.", "and migrate dorsolaterally. nevertheless", "dorsolaterally. nevertheless melanocytes", "nevertheless melanocytes can", "melanocytes can also arise", "can also arise in", "also arise in an", "arise in an alternate", "in an alternate pathway", "an alternate pathway from", "alternate pathway from dual", "pathway from dual schwann", "from dual schwann cell/melanocyte", "dual schwann cell/melanocyte precursors", "schwann cell/melanocyte precursors or", "cell/melanocyte precursors or by", "precursors or by dedifferentiation", "or by dedifferentiation from", "by dedifferentiation from schwann", "dedifferentiation from schwann cells", "schwann cells a", "cells a derivative", "a derivative of the", "derivative of the glial", "of the glial lineage", "glial lineage reviewed", "lineage reviewed in", "reviewed in mort et", "in mort et al", "et al 2015", "al 2015 .", "2015 . mitf m", ". mitf m is", "mitf m is a", "m is a key", "is a key regulator", "a key regulator of", "key regulator of melanocyte", "regulator of melanocyte development", "melanocyte development and", "development and its", "and its expression distinguishes", "its expression distinguishes the", "expression distinguishes the melanocyte", "distinguishes the melanocyte fate", "the melanocyte fate from", "melanocyte fate from that", "fate from that of", "from that of glial", "that of glial and", "of glial and neural", "glial and neural cells.", "and neural cells. mitf", "neural cells. mitf m", "cells. mitf m expression", "mitf m expression is", "m expression is repressed", "expression is repressed in", "is repressed in precursors", "repressed in precursors through", "in precursors through the", "precursors through the activity", "through the activity of", "the activity of foxd3", "activity of foxd3 and", "of foxd3 and sox2.", "foxd3 and sox2. depending", "and sox2. depending on", "sox2. depending on the", "depending on the species", "the species these", "species these transcription", "these transcription factors may", "transcription factors may either", "factors may either bind", "may either bind directly", "either bind directly to", "bind directly to elements", "directly to elements in", "to elements in the", "elements in the mitf", "in the mitf m", "the mitf m promoter", "mitf m promoter to", "m promoter to repress", "promoter to repress transcription", "repress transcription or", "transcription or may", "or may act independently", "may act independently of", "act independently of dna", "independently of dna binding", "of dna binding by", "dna binding by disrupting", "binding by disrupting protein", "by disrupting protein protein", "disrupting protein protein interactions", "protein protein interactions that", "protein interactions that promote", "interactions that promote transcriptional", "that promote transcriptional activity", "transcriptional activity nitzan", "activity nitzan et", "et al 2013a", "al 2013a b", "2013a b curran", "b curran et", "et al 2009", "2010 adameyko et", "et al 2012", "2012 reviewed in", "2015 white and", "and zon 2008", "2008 goding and", "and arnheiter 2019", "arnheiter 2019 .", "2019 . foxd3 and", ". foxd3 and sox2", "foxd3 and sox2 expression", "sox2 expression in", "expression in turn", "in turn are", "turn are regulated", "are regulated by a", "regulated by a cascade", "by a cascade of", "a cascade of other", "cascade of other transcription", "of other transcription factors", "transcription factors including", "factors including zic1", "including zic1 pax3", "pax3 snail2 and", "and sox9 reviewed", "sox9 reviewed in", "2015 goding and", "2019 .
              relief of", ".
              relief of foxd3", "
              relief of foxd3 mediated", "of foxd3 mediated repression", "foxd3 mediated repression may", "mediated repression may depend", "repression may depend in", "may depend in part", "depend in part on", "in part on hdac1", "on hdac1 as", "hdac1 as well", "as well as on", "well as on down", "as on down regulation", "on down regulation of", "down regulation of snail2", "of snail2 ignatius", "snail2 ignatius et", "et al 2008", "2008 greenhill et", "et al 2011", "2011 nitzan et", "2013a b .", "b . mitf m", ". mitf m expression", "mitf m expression in", "m expression in unpigmented", "expression in unpigmented but", "in unpigmented but committed", "unpigmented but committed melanoblasts", "but committed melanoblasts depends", "committed melanoblasts depends on", "melanoblasts depends on pax3", "depends on pax3 and", "on pax3 and sox10", "pax3 and sox10 binding", "and sox10 binding at", "sox10 binding at the", "binding at the promoter", "at the promoter as", "the promoter as well", "promoter as well as", "well as on wnt", "on wnt ednrb", "wnt ednrb and", "ednrb and kit signaling", "kit signaling reviewed", "signaling reviewed in", "2019 . initial expression", ". initial expression of", "initial expression of mitf", "expression of mitf m", "of mitf m also", "mitf m also contributes", "m also contributes to", "also contributes to downregulation", "contributes to downregulation of", "to downregulation of foxd3", "downregulation of foxd3 and", "of foxd3 and sox2", "foxd3 and sox2 establishing", "and sox2 establishing a", "sox2 establishing a positive", "establishing a positive feedback", "a positive feedback loop", "positive feedback loop that", "feedback loop that reinforces", "loop that reinforces commitment", "that reinforces commitment to", "reinforces commitment to the", "commitment to the melanocyte", "to the melanocyte fate", "melanocyte fate reviewed", "fate reviewed in", "arnheiter 2019 .
              in", "2019 .
              in addition to", ".
              in addition to transcriptional", "addition to transcriptional regulation", "transcriptional regulation mitf", "regulation mitf m", "mitf m activity is", "m activity is also", "activity is also controlled", "is also controlled by", "also controlled by post", "controlled by post translational", "by post translational modifications", "translational modifications although", "modifications although the", "although the significance of", "the significance of these", "significance of these modifications", "of these modifications is", "these modifications is not", "modifications is not always", "is not always clear.", "not always clear. sumoylation", "clear. sumoylation ubiquitination", "sumoylation ubiquitination and", "ubiquitination and phosphorylation downstream", "and phosphorylation downstream of", "phosphorylation downstream of mapk", "of mapk wnt", "mapk wnt and", "wnt and akt signaling", "and akt signaling can", "akt signaling can all", "signaling can all impact", "can all impact the", "all impact the stability", "the stability localization", "stability localization or", "localization or activity of", "or activity of mitf", "activity of mitf m", "mitf m reviewed", "m reviewed in", "reviewed in goding and", "in goding and arnheiter", "2019 and", "and acetylation regulates the", "acetylation regulates the occupancy", "regulates the occupancy of", "the occupancy of target", "occupancy of target promoters", "target promoters decreasing", "promoters decreasing occupancy", "decreasing occupancy at differentiation", "occupancy at differentiation specific", "at differentiation specific promoters", "specific promoters louphrasitthiphol", "promoters louphrasitthiphol et", "et al 2020", "2020 2023 .", "melanocytes neurons and glia", "neurons and glia all arise", "and glia all arise from", "glia all arise from precursor", "all arise from precursor cells", "arise from precursor cells derived", "from precursor cells derived from", "precursor cells derived from neural", "cells derived from neural crest", "derived from neural crest cells.", "from neural crest cells. cells", "neural crest cells. cells that", "crest cells. cells that will", "cells. cells that will give", "cells that will give rise", "that will give rise to", "will give rise to neurons", "give rise to neurons and", "rise to neurons and glia", "to neurons and glia migrate", "neurons and glia migrate away", "and glia migrate away from", "glia migrate away from the", "migrate away from the neural", "away from the neural crest", "from the neural crest earlier", "the neural crest earlier and", "neural crest earlier and in", "crest earlier and in a", "earlier and in a ventral", "and in a ventral pattern", "a ventral pattern while", "ventral pattern while cells", "pattern while cells that", "while cells that will give", "will give rise to melanocytes", "give rise to melanocytes leave", "rise to melanocytes leave the", "to melanocytes leave the neural", "melanocytes leave the neural crest", "leave the neural crest later", "the neural crest later and", "neural crest later and migrate", "crest later and migrate dorsolaterally.", "later and migrate dorsolaterally. nevertheless", "migrate dorsolaterally. nevertheless melanocytes", "dorsolaterally. nevertheless melanocytes can", "nevertheless melanocytes can also", "melanocytes can also arise in", "can also arise in an", "also arise in an alternate", "arise in an alternate pathway", "in an alternate pathway from", "an alternate pathway from dual", "alternate pathway from dual schwann", "pathway from dual schwann cell/melanocyte", "from dual schwann cell/melanocyte precursors", "dual schwann cell/melanocyte precursors or", "schwann cell/melanocyte precursors or by", "cell/melanocyte precursors or by dedifferentiation", "precursors or by dedifferentiation from", "or by dedifferentiation from schwann", "by dedifferentiation from schwann cells", "from schwann cells a", "schwann cells a derivative", "cells a derivative of", "a derivative of the glial", "derivative of the glial lineage", "the glial lineage reviewed", "glial lineage reviewed in", "lineage reviewed in mort", "reviewed in mort et al", "mort et al 2015", "et al 2015 .", "al 2015 . mitf", "2015 . mitf m is", ". mitf m is a", "mitf m is a key", "m is a key regulator", "is a key regulator of", "a key regulator of melanocyte", "key regulator of melanocyte development", "of melanocyte development and", "melanocyte development and its", "development and its expression", "and its expression distinguishes the", "its expression distinguishes the melanocyte", "expression distinguishes the melanocyte fate", "distinguishes the melanocyte fate from", "the melanocyte fate from that", "melanocyte fate from that of", "fate from that of glial", "from that of glial and", "that of glial and neural", "of glial and neural cells.", "glial and neural cells. mitf", "and neural cells. mitf m", "neural cells. mitf m expression", "cells. mitf m expression is", "mitf m expression is repressed", "m expression is repressed in", "expression is repressed in precursors", "is repressed in precursors through", "repressed in precursors through the", "in precursors through the activity", "precursors through the activity of", "through the activity of foxd3", "the activity of foxd3 and", "activity of foxd3 and sox2.", "of foxd3 and sox2. depending", "foxd3 and sox2. depending on", "and sox2. depending on the", "sox2. depending on the species", "on the species these", "the species these transcription", "species these transcription factors", "these transcription factors may either", "transcription factors may either bind", "factors may either bind directly", "may either bind directly to", "either bind directly to elements", "bind directly to elements in", "directly to elements in the", "to elements in the mitf", "elements in the mitf m", "in the mitf m promoter", "the mitf m promoter to", "mitf m promoter to repress", "m promoter to repress transcription", "to repress transcription or", "repress transcription or may", "transcription or may act", "or may act independently of", "may act independently of dna", "act independently of dna binding", "independently of dna binding by", "of dna binding by disrupting", "dna binding by disrupting protein", "binding by disrupting protein protein", "by disrupting protein protein interactions", "disrupting protein protein interactions that", "protein protein interactions that promote", "protein interactions that promote transcriptional", "interactions that promote transcriptional activity", "promote transcriptional activity nitzan", "transcriptional activity nitzan et", "activity nitzan et al", "nitzan et al 2013a", "et al 2013a b", "2013a b curran et", "b curran et al", "curran et al 2009", "al 2009 2010", "2009 2010 adameyko", "2010 adameyko et al", "adameyko et al 2012", "al 2012 reviewed", "2012 reviewed in mort", "al 2015 white", "2015 white and zon", "white and zon 2008", "zon 2008 goding", "2008 goding and arnheiter", "goding and arnheiter 2019", "and arnheiter 2019 .", "arnheiter 2019 . foxd3", "2019 . foxd3 and sox2", ". foxd3 and sox2 expression", "and sox2 expression in", "sox2 expression in turn", "in turn are regulated", "turn are regulated by", "are regulated by a cascade", "regulated by a cascade of", "by a cascade of other", "a cascade of other transcription", "cascade of other transcription factors", "other transcription factors including", "transcription factors including zic1", "zic1 pax3 snail2", "pax3 snail2 and sox9", "snail2 and sox9 reviewed", "and sox9 reviewed in", "sox9 reviewed in mort", "al 2015 goding", "2015 goding and arnheiter", "arnheiter 2019 .
              relief", "2019 .
              relief of foxd3", ".
              relief of foxd3 mediated", "
              relief of foxd3 mediated repression", "of foxd3 mediated repression may", "foxd3 mediated repression may depend", "mediated repression may depend in", "repression may depend in part", "may depend in part on", "depend in part on hdac1", "part on hdac1 as", "on hdac1 as well", "hdac1 as well as", "as well as on down", "well as on down regulation", "as on down regulation of", "on down regulation of snail2", "regulation of snail2 ignatius", "of snail2 ignatius et", "snail2 ignatius et al", "ignatius et al 2008", "al 2008 greenhill", "2008 greenhill et al", "greenhill et al 2011", "al 2011 nitzan", "2011 nitzan et al", "2013a b . mitf", "b . mitf m expression", ". mitf m expression in", "mitf m expression in unpigmented", "m expression in unpigmented but", "expression in unpigmented but committed", "in unpigmented but committed melanoblasts", "unpigmented but committed melanoblasts depends", "but committed melanoblasts depends on", "committed melanoblasts depends on pax3", "melanoblasts depends on pax3 and", "depends on pax3 and sox10", "on pax3 and sox10 binding", "pax3 and sox10 binding at", "and sox10 binding at the", "sox10 binding at the promoter", "binding at the promoter as", "at the promoter as well", "the promoter as well as", "promoter as well as on", "as well as on wnt", "as on wnt ednrb", "on wnt ednrb and", "wnt ednrb and kit", "and kit signaling reviewed", "kit signaling reviewed in", "signaling reviewed in mort", "arnheiter 2019 . initial", "2019 . initial expression of", ". initial expression of mitf", "initial expression of mitf m", "expression of mitf m also", "of mitf m also contributes", "mitf m also contributes to", "m also contributes to downregulation", "also contributes to downregulation of", "contributes to downregulation of foxd3", "to downregulation of foxd3 and", "downregulation of foxd3 and sox2", "of foxd3 and sox2 establishing", "foxd3 and sox2 establishing a", "and sox2 establishing a positive", "sox2 establishing a positive feedback", "establishing a positive feedback loop", "a positive feedback loop that", "positive feedback loop that reinforces", "feedback loop that reinforces commitment", "loop that reinforces commitment to", "that reinforces commitment to the", "reinforces commitment to the melanocyte", "commitment to the melanocyte fate", "the melanocyte fate reviewed", "melanocyte fate reviewed in", "fate reviewed in mort", "and arnheiter 2019 .
              in", "arnheiter 2019 .
              in addition", "2019 .
              in addition to transcriptional", ".
              in addition to transcriptional regulation", "to transcriptional regulation mitf", "transcriptional regulation mitf m", "regulation mitf m activity", "mitf m activity is also", "m activity is also controlled", "activity is also controlled by", "is also controlled by post", "also controlled by post translational", "controlled by post translational modifications", "post translational modifications although", "translational modifications although the", "modifications although the significance", "although the significance of these", "the significance of these modifications", "significance of these modifications is", "of these modifications is not", "these modifications is not always", "modifications is not always clear.", "is not always clear. sumoylation", "always clear. sumoylation ubiquitination", "clear. sumoylation ubiquitination and", "sumoylation ubiquitination and phosphorylation", "ubiquitination and phosphorylation downstream of", "and phosphorylation downstream of mapk", "downstream of mapk wnt", "of mapk wnt and", "mapk wnt and akt", "wnt and akt signaling can", "and akt signaling can all", "akt signaling can all impact", "signaling can all impact the", "can all impact the stability", "impact the stability localization", "the stability localization or", "stability localization or activity", "localization or activity of mitf", "or activity of mitf m", "of mitf m reviewed", "mitf m reviewed in", "m reviewed in goding", "reviewed in goding and arnheiter", "2019 and acetylation", "and acetylation regulates the occupancy", "acetylation regulates the occupancy of", "regulates the occupancy of target", "the occupancy of target promoters", "of target promoters decreasing", "target promoters decreasing occupancy", "promoters decreasing occupancy at", "decreasing occupancy at differentiation specific", "occupancy at differentiation specific promoters", "differentiation specific promoters louphrasitthiphol", "specific promoters louphrasitthiphol et", "promoters louphrasitthiphol et al", "louphrasitthiphol et al 2020", "al 2020 2023", "2020 2023 .
              " ] }, { "record_id": "GLY_000594_1_2130", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9856872", "r hsa", "hsa 9856872", "r hsa 9856872" ] }, { "record_id": "GLY_000594_1_2130", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "malate aspartate", "aspartate shuttle", "malate aspartate shuttle", "the malate", "is a", "a redox", "redox process", "process that", "that supports", "supports oxidative", "oxidative pathways", "pathways in", "in the", "the cytosol", "and reductive", "reductive potential", "potential in", "in mitochondria.", "mitochondria. the", "the mitochondrial", "mitochondrial succinate", "succinate dehydrogenase", "reaction provides", "provides reducing", "reducing equivalents", "for the", "the respiratory", "respiratory electron", "electron transport", "with the", "the nadh", "nadh needed", "needed to", "to reduce", "reduce malate", "malate coming", "coming from", "from cytosolic", "cytosolic processes.", "processes. there", "there is", "is no", "no nadh", "nadh equilibrium", "equilibrium between", "between cytosol", "cytosol and", "and mitochondria:", "mitochondria: cytosolic", "cytosolic nadh/nad+", "nadh/nad+ ratio", "ratio is", "is 0.001", "while in", "in mitochondria", "it is", "is 0.1.", "0.1. the", "the mas", "mas creates", "creates this", "this nadh", "nadh gradient", "gradient by", "by reducing", "reducing oxaloacetate", "to malate", "catalyzed by", "by cytosolic", "cytosolic mdh1", "and exchanging", "exchanging cytosolic", "cytosolic mal", "mal with", "with mitochondrial", "mitochondrial 2", "2 oxoglutarate", "2 kg", "by slc25a11.", "slc25a11. at", "at the", "the same", "same time", "l asp", "gets exported", "exported and", "and transaminated", "transaminated to", "to glutamate", "l glu", "which subsequently", "subsequently gets", "gets coimported", "coimported with", "with a", "a proton", "proton and", "transaminated back.", "back. in", "in summary", "mitochondria take", "take up", "up one", "one proton", "and one", "one reducing", "reducing equivalent.", "equivalent. the", "the proton", "proton import", "import by", "by slc25a12/13", "slc25a12/13 is", "is irreversible", "so the", "mas always", "always runs", "runs in", "in one", "one direction.", "direction. hence", "mitochondrial outward", "outward proton", "proton motive", "motive force", "force drives", "drives the", "mas toward", "toward cytosolic", "cytosolic nadh", "nadh oxidation.", "oxidation. defects", "defects in", "in any", "any of", "of the", "the reactions", "reactions of", "of this", "this pathway", "pathway lead", "lead to", "to cytosolic", "cytosolic nad+", "nad+ scarcity", "affecting glycolysis", "and l", "l ser", "ser biosynthesis", "as well", "well as", "as l", "asp availability.", "availability. neurotransmission", "neurotransmission in", "the cns", "cns specifically", "specifically needs", "needs l", "asp and", "and mutations", "mutations in", "in proteins", "proteins catalyzing", "catalyzing mas", "mas reactions", "reactions are", "are commonly", "commonly associated", "associated with", "with early", "early infantile", "infantile epileptic", "epileptic encephalopathy", "reviewed in", "in borst", "broeks et", "et al.", "2021 .", "the malate aspartate", "shuttle mas", "mas is", "is a redox", "a redox process", "redox process that", "process that supports", "that supports oxidative", "supports oxidative pathways", "oxidative pathways in", "pathways in the", "in the cytosol", "and reductive potential", "reductive potential in", "potential in mitochondria.", "in mitochondria. the", "mitochondria. the mitochondrial", "the mitochondrial succinate", "mitochondrial succinate dehydrogenase", "dehydrogenase sdh", "sdh reaction", "reaction provides reducing", "provides reducing equivalents", "equivalents electrons", "electrons for", "for the respiratory", "the respiratory electron", "respiratory electron transport", "transport with", "with the nadh", "the nadh needed", "nadh needed to", "needed to reduce", "to reduce malate", "reduce malate coming", "malate coming from", "coming from cytosolic", "from cytosolic processes.", "cytosolic processes. there", "processes. there is", "there is no", "is no nadh", "no nadh equilibrium", "nadh equilibrium between", "equilibrium between cytosol", "between cytosol and", "cytosol and mitochondria:", "and mitochondria: cytosolic", "mitochondria: cytosolic nadh/nad+", "cytosolic nadh/nad+ ratio", "nadh/nad+ ratio is", "ratio is 0.001", "0.001 while", "while in mitochondria", "mitochondria it", "it is 0.1.", "is 0.1. the", "0.1. the mas", "the mas creates", "mas creates this", "creates this nadh", "this nadh gradient", "nadh gradient by", "gradient by reducing", "by reducing oxaloacetate", "oxaloacetate oa", "oa to", "malate mal", "catalyzed by cytosolic", "by cytosolic mdh1", "mdh1 and", "and exchanging cytosolic", "exchanging cytosolic mal", "cytosolic mal with", "mal with mitochondrial", "with mitochondrial 2", "mitochondrial 2 oxoglutarate", "oxoglutarate 2og", "2og 2", "catalyzed by slc25a11.", "by slc25a11. at", "slc25a11. at the", "at the same", "the same time", "time aspartate", "aspartate l", "asp gets", "gets exported and", "exported and transaminated", "and transaminated to", "transaminated to glutamate", "glutamate l", "which subsequently gets", "subsequently gets coimported", "gets coimported with", "coimported with a", "with a proton", "a proton and", "proton and transaminated", "and transaminated back.", "transaminated back. in", "back. in summary", "summary mitochondria", "mitochondria take up", "take up one", "up one proton", "one proton and", "proton and one", "and one reducing", "one reducing equivalent.", "reducing equivalent. the", "equivalent. the proton", "the proton import", "proton import by", "import by slc25a12/13", "by slc25a12/13 is", "slc25a12/13 is irreversible", "irreversible so", "so the mas", "the mas always", "mas always runs", "always runs in", "runs in one", "in one direction.", "one direction. hence", "hence the", "the mitochondrial outward", "mitochondrial outward proton", "outward proton motive", "proton motive force", "motive force drives", "force drives the", "drives the mas", "the mas toward", "mas toward cytosolic", "toward cytosolic nadh", "cytosolic nadh oxidation.", "nadh oxidation. defects", "oxidation. defects in", "defects in any", "in any of", "any of the", "of the reactions", "the reactions of", "reactions of this", "of this pathway", "this pathway lead", "pathway lead to", "lead to cytosolic", "to cytosolic nad+", "cytosolic nad+ scarcity", "scarcity affecting", "glycolysis l", "glu and", "and l ser", "l ser biosynthesis", "biosynthesis as", "as well as", "well as l", "as l asp", "l asp availability.", "asp availability. neurotransmission", "availability. neurotransmission in", "neurotransmission in the", "in the cns", "the cns specifically", "cns specifically needs", "specifically needs l", "needs l asp", "l asp and", "asp and l", "and l glu", "and mutations in", "mutations in proteins", "in proteins catalyzing", "proteins catalyzing mas", "catalyzing mas reactions", "mas reactions are", "reactions are commonly", "are commonly associated", "commonly associated with", "associated with early", "with early infantile", "early infantile epileptic", "infantile epileptic encephalopathy", "encephalopathy reviewed", "reviewed in borst", "borst 2020", "2020 broeks", "broeks et al.", "al. 2021", "the malate aspartate shuttle", "aspartate shuttle mas", "mas is a", "is a redox process", "a redox process that", "redox process that supports", "process that supports oxidative", "that supports oxidative pathways", "supports oxidative pathways in", "oxidative pathways in the", "pathways in the cytosol", "the cytosol and", "cytosol and reductive", "and reductive potential in", "reductive potential in mitochondria.", "potential in mitochondria. the", "in mitochondria. the mitochondrial", "mitochondria. the mitochondrial succinate", "the mitochondrial succinate dehydrogenase", "succinate dehydrogenase sdh", "sdh reaction provides", "reaction provides reducing equivalents", "reducing equivalents electrons", "electrons for the", "for the respiratory electron", "the respiratory electron transport", "electron transport with", "transport with the", "with the nadh needed", "the nadh needed to", "nadh needed to reduce", "needed to reduce malate", "to reduce malate coming", "reduce malate coming from", "malate coming from cytosolic", "coming from cytosolic processes.", "from cytosolic processes. there", "cytosolic processes. there is", "processes. there is no", "there is no nadh", "is no nadh equilibrium", "no nadh equilibrium between", "nadh equilibrium between cytosol", "equilibrium between cytosol and", "between cytosol and mitochondria:", "cytosol and mitochondria: cytosolic", "and mitochondria: cytosolic nadh/nad+", "mitochondria: cytosolic nadh/nad+ ratio", "cytosolic nadh/nad+ ratio is", "nadh/nad+ ratio is 0.001", "is 0.001 while", "0.001 while in", "in mitochondria it", "mitochondria it is", "it is 0.1. the", "is 0.1. the mas", "0.1. the mas creates", "the mas creates this", "mas creates this nadh", "creates this nadh gradient", "this nadh gradient by", "nadh gradient by reducing", "gradient by reducing oxaloacetate", "reducing oxaloacetate oa", "oa to malate", "to malate mal", "mal catalyzed", "catalyzed by cytosolic mdh1", "cytosolic mdh1 and", "mdh1 and exchanging", "and exchanging cytosolic mal", "exchanging cytosolic mal with", "cytosolic mal with mitochondrial", "mal with mitochondrial 2", "with mitochondrial 2 oxoglutarate", "2 oxoglutarate 2og", "2og 2 kg", "kg catalyzed", "catalyzed by slc25a11. at", "by slc25a11. at the", "slc25a11. at the same", "at the same time", "same time aspartate", "aspartate l asp", "l asp gets", "asp gets exported", "gets exported and transaminated", "exported and transaminated to", "and transaminated to glutamate", "to glutamate l", "glutamate l glu", "glu which", "which subsequently gets coimported", "subsequently gets coimported with", "gets coimported with a", "coimported with a proton", "with a proton and", "a proton and transaminated", "proton and transaminated back.", "and transaminated back. in", "transaminated back. in summary", "in summary mitochondria", "summary mitochondria take", "mitochondria take up one", "take up one proton", "up one proton and", "one proton and one", "proton and one reducing", "and one reducing equivalent.", "one reducing equivalent. the", "reducing equivalent. the proton", "equivalent. the proton import", "the proton import by", "proton import by slc25a12/13", "import by slc25a12/13 is", "by slc25a12/13 is irreversible", "is irreversible so", "irreversible so the", "so the mas always", "the mas always runs", "mas always runs in", "always runs in one", "runs in one direction.", "in one direction. hence", "direction. hence the", "hence the mitochondrial", "the mitochondrial outward proton", "mitochondrial outward proton motive", "outward proton motive force", "proton motive force drives", "motive force drives the", "force drives the mas", "drives the mas toward", "the mas toward cytosolic", "mas toward cytosolic nadh", "toward cytosolic nadh oxidation.", "cytosolic nadh oxidation. defects", "nadh oxidation. defects in", "oxidation. defects in any", "defects in any of", "in any of the", "any of the reactions", "of the reactions of", "the reactions of this", "reactions of this pathway", "of this pathway lead", "this pathway lead to", "pathway lead to cytosolic", "lead to cytosolic nad+", "to cytosolic nad+ scarcity", "nad+ scarcity affecting", "scarcity affecting glycolysis", "affecting glycolysis l", "glycolysis l glu", "l glu and", "glu and l", "and l ser biosynthesis", "ser biosynthesis as", "biosynthesis as well", "as well as l", "well as l asp", "as l asp availability.", "l asp availability. neurotransmission", "asp availability. neurotransmission in", "availability. neurotransmission in the", "neurotransmission in the cns", "in the cns specifically", "the cns specifically needs", "cns specifically needs l", "specifically needs l asp", "needs l asp and", "l asp and l", "asp and l glu", "glu and mutations", "and mutations in proteins", "mutations in proteins catalyzing", "in proteins catalyzing mas", "proteins catalyzing mas reactions", "catalyzing mas reactions are", "mas reactions are commonly", "reactions are commonly associated", "are commonly associated with", "commonly associated with early", "associated with early infantile", "with early infantile epileptic", "early infantile epileptic encephalopathy", "epileptic encephalopathy reviewed", "encephalopathy reviewed in", "in borst 2020", "2020 broeks et", "et al. 2021", "al. 2021 .", "malate aspartate shuttle mas", "shuttle mas is", "mas is a redox", "is a redox process that", "a redox process that supports", "redox process that supports oxidative", "process that supports oxidative pathways", "that supports oxidative pathways in", "supports oxidative pathways in the", "oxidative pathways in the cytosol", "in the cytosol and", "the cytosol and reductive", "cytosol and reductive potential", "and reductive potential in mitochondria.", "reductive potential in mitochondria. the", "potential in mitochondria. the mitochondrial", "in mitochondria. the mitochondrial succinate", "mitochondria. the mitochondrial succinate dehydrogenase", "mitochondrial succinate dehydrogenase sdh", "dehydrogenase sdh reaction", "sdh reaction provides reducing", "provides reducing equivalents electrons", "equivalents electrons for", "electrons for the respiratory", "for the respiratory electron transport", "respiratory electron transport with", "electron transport with the", "transport with the nadh", "with the nadh needed to", "the nadh needed to reduce", "nadh needed to reduce malate", "needed to reduce malate coming", "to reduce malate coming from", "reduce malate coming from cytosolic", "malate coming from cytosolic processes.", "coming from cytosolic processes. there", "from cytosolic processes. there is", "cytosolic processes. there is no", "processes. there is no nadh", "there is no nadh equilibrium", "is no nadh equilibrium between", "no nadh equilibrium between cytosol", "nadh equilibrium between cytosol and", "equilibrium between cytosol and mitochondria:", "between cytosol and mitochondria: cytosolic", "cytosol and mitochondria: cytosolic nadh/nad+", "and mitochondria: cytosolic nadh/nad+ ratio", "mitochondria: cytosolic nadh/nad+ ratio is", "cytosolic nadh/nad+ ratio is 0.001", "ratio is 0.001 while", "is 0.001 while in", "0.001 while in mitochondria", "while in mitochondria it", "in mitochondria it is", "mitochondria it is 0.1.", "it is 0.1. the mas", "is 0.1. the mas creates", "0.1. the mas creates this", "the mas creates this nadh", "mas creates this nadh gradient", "creates this nadh gradient by", "this nadh gradient by reducing", "nadh gradient by reducing oxaloacetate", "by reducing oxaloacetate oa", "oxaloacetate oa to", "mal catalyzed by", "by cytosolic mdh1 and", "cytosolic mdh1 and exchanging", "mdh1 and exchanging cytosolic", "and exchanging cytosolic mal with", "exchanging cytosolic mal with mitochondrial", "cytosolic mal with mitochondrial 2", "mal with mitochondrial 2 oxoglutarate", "mitochondrial 2 oxoglutarate 2og", "oxoglutarate 2og 2", "2 kg catalyzed", "kg catalyzed by", "catalyzed by slc25a11. at the", "by slc25a11. at the same", "slc25a11. at the same time", "the same time aspartate", "time aspartate l", "l asp gets exported", "asp gets exported and", "gets exported and transaminated to", "exported and transaminated to glutamate", "transaminated to glutamate l", "to glutamate l glu", "l glu which", "glu which subsequently", "which subsequently gets coimported with", "subsequently gets coimported with a", "gets coimported with a proton", "coimported with a proton and", "with a proton and transaminated", "a proton and transaminated back.", "proton and transaminated back. in", "and transaminated back. in summary", "back. in summary mitochondria", "in summary mitochondria take", "summary mitochondria take up", "mitochondria take up one proton", "take up one proton and", "up one proton and one", "one proton and one reducing", "proton and one reducing equivalent.", "and one reducing equivalent. the", "one reducing equivalent. the proton", "reducing equivalent. the proton import", "equivalent. the proton import by", "the proton import by slc25a12/13", "proton import by slc25a12/13 is", "import by slc25a12/13 is irreversible", "slc25a12/13 is irreversible so", "is irreversible so the", "irreversible so the mas", "so the mas always runs", "the mas always runs in", "mas always runs in one", "always runs in one direction.", "runs in one direction. hence", "one direction. hence the", "direction. hence the mitochondrial", "hence the mitochondrial outward", "the mitochondrial outward proton motive", "mitochondrial outward proton motive force", "outward proton motive force drives", "proton motive force drives the", "motive force drives the mas", "force drives the mas toward", "drives the mas toward cytosolic", "the mas toward cytosolic nadh", "mas toward cytosolic nadh oxidation.", "toward cytosolic nadh oxidation. defects", "cytosolic nadh oxidation. defects in", "nadh oxidation. defects in any", "oxidation. defects in any of", "defects in any of the", "in any of the reactions", "any of the reactions of", "of the reactions of this", "the reactions of this pathway", "reactions of this pathway lead", "of this pathway lead to", "this pathway lead to cytosolic", "pathway lead to cytosolic nad+", "lead to cytosolic nad+ scarcity", "cytosolic nad+ scarcity affecting", "nad+ scarcity affecting glycolysis", "affecting glycolysis l glu", "l glu and l", "glu and l ser", "l ser biosynthesis as", "ser biosynthesis as well", "biosynthesis as well as", "as well as l asp", "well as l asp availability.", "as l asp availability. neurotransmission", "l asp availability. neurotransmission in", "asp availability. neurotransmission in the", "availability. neurotransmission in the cns", "neurotransmission in the cns specifically", "in the cns specifically needs", "the cns specifically needs l", "cns specifically needs l asp", "specifically needs l asp and", "needs l asp and l", "l asp and l glu", "and l glu and", "l glu and mutations", "glu and mutations in", "and mutations in proteins catalyzing", "mutations in proteins catalyzing mas", "in proteins catalyzing mas reactions", "proteins catalyzing mas reactions are", "catalyzing mas reactions are commonly", "mas reactions are commonly associated", "reactions are commonly associated with", "are commonly associated with early", "commonly associated with early infantile", "associated with early infantile epileptic", "with early infantile epileptic encephalopathy", "infantile epileptic encephalopathy reviewed", "epileptic encephalopathy reviewed in", "encephalopathy reviewed in borst", "reviewed in borst 2020", "borst 2020 broeks", "2020 broeks et al.", "broeks et al. 2021", "et al. 2021 ." ] }, { "record_id": "GLY_000594_1_2131", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9861718", "r hsa", "hsa 9861718", "r hsa 9861718" ] }, { "record_id": "GLY_000594_1_2131", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "regulation of", "of pyruvate", "pyruvate metabolism", "regulation of pyruvate", "of pyruvate metabolism", "regulation of pyruvate metabolism", "this subpathway", "subpathway collects", "collects reactions", "reactions regulating", "regulating pyruvate", "pyruvate metabolism.", "this subpathway collects", "subpathway collects reactions", "collects reactions regulating", "reactions regulating pyruvate", "regulating pyruvate metabolism.", "this subpathway collects reactions", "subpathway collects reactions regulating", "collects reactions regulating pyruvate", "reactions regulating pyruvate metabolism.", "this subpathway collects reactions regulating", "subpathway collects reactions regulating pyruvate", "collects reactions regulating pyruvate metabolism." ] }, { "record_id": "GLY_000594_1_2132", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9820962", "r hsa", "hsa 9820962", "r hsa 9820962" ] }, { "record_id": "GLY_000594_1_2132", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "assembly and", "and release", "release of", "of respiratory", "respiratory syncytial", "syncytial virus", "assembly and release", "and release of", "release of respiratory", "of respiratory syncytial", "respiratory syncytial virus", "virus rsv", "rsv virions", "assembly and release of", "and release of respiratory", "release of respiratory syncytial", "of respiratory syncytial virus", "syncytial virus rsv", "assembly and release of respiratory", "and release of respiratory syncytial", "release of respiratory syncytial virus", "respiratory syncytial virus rsv", "virus rsv virions", "a mature", "mature virion", "virion of", "of the", "the respiratory", "consists of", "the ribonucleoprotein", "ribonucleoprotein complex", "surrounded by", "by the", "the protein", "protein matrix", "matrix and", "and a", "a lipid", "lipid bilayer", "bilayer envelope.", "envelope. the", "the rnp", "rnp is", "is composed", "composed of", "the genomic", "genomic negative", "negative sense", "sense single", "single stranded", "that is", "is tightly", "tightly associated", "associated with", "with the", "the n", "n protein", "and the", "the rna", "rna dependent", "dependent rna", "rna polymerase", "polymerase complex", "rdrp .", ". the", "the rdrp", "rdrp consists", "the l", "l protein", "protein subunit", "large polymerase", "polymerase subunit", "the p", "p protein", "phosphoprotein polymerase", "polymerase cofactor", "the m2", "m2 1", "1 protein", "which acts", "acts as", "as a", "a transcription", "transcription processivity", "processivity factor.", "factor. the", "the matrix", "matrix consists", "the m", "protein. the", "protein serves", "serves as", "as the", "the bridge", "bridge between", "between the", "rnp and", "m protein.", "matrix supports", "supports the", "the viral", "viral envelope.", "viral envelope", "envelope contains", "contains three", "three embedded", "embedded viral", "viral proteins:", "proteins: fusion", "fusion protein", "attachment protein", "a small", "small hydrophobic", "hydrophobic protein", "sh .", "m protein", "protein associates", "associates with", "the cytoplasmic", "cytoplasmic domain", "domain of", "the f", "f protein.", "the sh", "sh protein", "protein forms", "forms a", "a pentameric", "pentameric ion", "ion channel", "channel in", "in the", "envelope and", "and is", "is thought", "thought to", "to delay", "delay apoptosis", "apoptosis of", "of infected", "infected cells.", "cells. the", "the assembly", "and budding", "budding of", "of rsv", "virions primarily", "primarily occurs", "occurs at", "at the", "the apical", "apical surface", "surface of", "of ciliated", "ciliated airway", "airway epithelial", "epithelial cells", "cells where", "where viral", "viral filaments", "filaments containing", "containing rnps", "rnps form.", "form. the", "the budding", "virions requires", "requires interactions", "interactions between", "between viral", "viral proteins", "host cytoskeletal", "cytoskeletal proteins", "and membrane.", "membrane. for", "for review", "please refer", "refer to", "to shaikh", "shaikh and", "and crowe", "crowe 2013", "and battles", "battles and", "and mclellan", "mclellan 2019.

              based", "2019.

              based on", "on the", "the findings", "findings that", "that p", "and f", "f proteins", "proteins are", "are sufficient", "sufficient for", "for formation", "formation of", "of viral\u2011like", "viral\u2011like particles", "particularly its", "its highly", "highly phosphorylated", "phosphorylated serine/threonine\u2011rich", "serine/threonine\u2011rich region", "region between", "between amino", "amino acids", "acids 39", "39 and", "and 57", "57 that", "that likely", "likely interacts", "interacts with", "with m", "m and/or", "and/or f", "may play", "play an", "an important", "important role", "role in", "meshram and", "and oomens", "oomens 2019", "2019 .", "a mature virion", "mature virion of", "virion of the", "of the respiratory", "the respiratory syncytial", "rsv consists", "consists of the", "of the ribonucleoprotein", "the ribonucleoprotein complex", "complex rnp", "rnp surrounded", "surrounded by the", "by the protein", "the protein matrix", "protein matrix and", "matrix and a", "and a lipid", "a lipid bilayer", "lipid bilayer envelope.", "bilayer envelope. the", "envelope. the rnp", "the rnp is", "rnp is composed", "is composed of", "composed of the", "of the genomic", "the genomic negative", "genomic negative sense", "negative sense single", "sense single stranded", "ssrna that", "that is tightly", "is tightly associated", "tightly associated with", "associated with the", "with the n", "the n protein", "protein nucleoprotein", "nucleoprotein and", "and the rna", "the rna dependent", "rna dependent rna", "dependent rna polymerase", "rna polymerase complex", "complex rdrp", "rdrp . the", ". the rdrp", "the rdrp consists", "rdrp consists of", "of the l", "the l protein", "l protein subunit", "subunit large", "large polymerase subunit", "the p protein", "p protein subunit", "subunit phosphoprotein", "phosphoprotein polymerase cofactor", "and the m2", "the m2 1", "m2 1 protein", "protein which", "which acts as", "acts as a", "as a transcription", "a transcription processivity", "transcription processivity factor.", "processivity factor. the", "factor. the matrix", "the matrix consists", "matrix consists of", "of the m", "m matrix", "matrix protein.", "protein. the m2", "1 protein serves", "protein serves as", "serves as the", "as the bridge", "the bridge between", "bridge between the", "between the rnp", "the rnp and", "rnp and the", "and the m", "the m protein.", "m protein. the", "protein. the matrix", "the matrix supports", "matrix supports the", "supports the viral", "the viral envelope.", "viral envelope. the", "envelope. the viral", "the viral envelope", "viral envelope contains", "envelope contains three", "contains three embedded", "three embedded viral", "embedded viral proteins:", "viral proteins: fusion", "proteins: fusion protein", "protein f", "protein g", "and a small", "a small hydrophobic", "small hydrophobic protein", "protein sh", "sh . the", ". the m", "the m protein", "m protein associates", "protein associates with", "associates with the", "with the cytoplasmic", "the cytoplasmic domain", "cytoplasmic domain of", "domain of the", "of the f", "the f protein.", "f protein. the", "protein. the sh", "the sh protein", "sh protein forms", "protein forms a", "forms a pentameric", "a pentameric ion", "pentameric ion channel", "ion channel in", "channel in the", "in the viral", "viral envelope and", "envelope and is", "and is thought", "is thought to", "thought to delay", "to delay apoptosis", "delay apoptosis of", "apoptosis of infected", "of infected cells.", "infected cells. the", "cells. the assembly", "the assembly and", "assembly and budding", "and budding of", "budding of rsv", "of rsv virions", "rsv virions primarily", "virions primarily occurs", "primarily occurs at", "occurs at the", "at the apical", "the apical surface", "apical surface of", "surface of ciliated", "of ciliated airway", "ciliated airway epithelial", "airway epithelial cells", "epithelial cells where", "cells where viral", "where viral filaments", "viral filaments containing", "filaments containing rnps", "containing rnps form.", "rnps form. the", "form. the budding", "the budding of", "rsv virions requires", "virions requires interactions", "requires interactions between", "interactions between viral", "between viral proteins", "proteins host", "host cytoskeletal proteins", "proteins and", "and membrane. for", "membrane. for review", "review please", "please refer to", "refer to shaikh", "to shaikh and", "shaikh and crowe", "and crowe 2013", "2013 and", "and battles and", "battles and mclellan", "and mclellan 2019.

              based", "mclellan 2019.

              based on", "2019.

              based on the", "on the findings", "the findings that", "findings that p", "p m", "m and", "and f proteins", "f proteins are", "proteins are sufficient", "are sufficient for", "sufficient for formation", "for formation of", "formation of viral\u2011like", "of viral\u2011like particles", "particles vlps", "protein particularly", "particularly its highly", "its highly phosphorylated", "highly phosphorylated serine/threonine\u2011rich", "phosphorylated serine/threonine\u2011rich region", "serine/threonine\u2011rich region between", "region between amino", "between amino acids", "amino acids 39", "acids 39 and", "39 and 57", "and 57 that", "57 that likely", "that likely interacts", "likely interacts with", "interacts with m", "with m and/or", "m and/or f", "and/or f proteins", "proteins may", "may play an", "play an important", "an important role", "important role in", "role in the", "in the assembly", "assembly meshram", "meshram and oomens", "and oomens 2019", "oomens 2019 .", "a mature virion of", "mature virion of the", "virion of the respiratory", "of the respiratory syncytial", "the respiratory syncytial virus", "rsv consists of", "consists of the ribonucleoprotein", "of the ribonucleoprotein complex", "ribonucleoprotein complex rnp", "rnp surrounded by", "surrounded by the protein", "by the protein matrix", "the protein matrix and", "protein matrix and a", "matrix and a lipid", "and a lipid bilayer", "a lipid bilayer envelope.", "lipid bilayer envelope. the", "bilayer envelope. the rnp", "envelope. the rnp is", "the rnp is composed", "rnp is composed of", "is composed of the", "composed of the genomic", "of the genomic negative", "the genomic negative sense", "genomic negative sense single", "negative sense single stranded", "stranded ssrna", "ssrna that is", "that is tightly associated", "is tightly associated with", "tightly associated with the", "associated with the n", "with the n protein", "n protein nucleoprotein", "nucleoprotein and the", "and the rna dependent", "the rna dependent rna", "rna dependent rna polymerase", "dependent rna polymerase complex", "polymerase complex rdrp", "complex rdrp .", "rdrp . the rdrp", ". the rdrp consists", "the rdrp consists of", "rdrp consists of the", "consists of the l", "of the l protein", "the l protein subunit", "protein subunit large", "subunit large polymerase", "subunit the", "the p protein subunit", "protein subunit phosphoprotein", "subunit phosphoprotein polymerase", "cofactor and", "and the m2 1", "the m2 1 protein", "1 protein which", "protein which acts", "which acts as a", "acts as a transcription", "as a transcription processivity", "a transcription processivity factor.", "transcription processivity factor. the", "processivity factor. the matrix", "factor. the matrix consists", "the matrix consists of", "matrix consists of the", "consists of the m", "the m matrix", "matrix protein. the", "protein. the m2 1", "m2 1 protein serves", "1 protein serves as", "protein serves as the", "serves as the bridge", "as the bridge between", "the bridge between the", "bridge between the rnp", "between the rnp and", "the rnp and the", "rnp and the m", "and the m protein.", "the m protein. the", "m protein. the matrix", "protein. the matrix supports", "the matrix supports the", "matrix supports the viral", "supports the viral envelope.", "the viral envelope. the", "viral envelope. the viral", "envelope. the viral envelope", "the viral envelope contains", "viral envelope contains three", "envelope contains three embedded", "contains three embedded viral", "three embedded viral proteins:", "embedded viral proteins: fusion", "viral proteins: fusion protein", "fusion protein f", "f attachment", "attachment protein g", "g and", "and a small hydrophobic", "a small hydrophobic protein", "hydrophobic protein sh", "protein sh .", "sh . the m", ". the m protein", "the m protein associates", "m protein associates with", "protein associates with the", "associates with the cytoplasmic", "with the cytoplasmic domain", "the cytoplasmic domain of", "cytoplasmic domain of the", "domain of the f", "of the f protein.", "the f protein. the", "f protein. the sh", "protein. the sh protein", "the sh protein forms", "sh protein forms a", "protein forms a pentameric", "forms a pentameric ion", "a pentameric ion channel", "pentameric ion channel in", "ion channel in the", "channel in the viral", "in the viral envelope", "the viral envelope and", "viral envelope and is", "envelope and is thought", "and is thought to", "is thought to delay", "thought to delay apoptosis", "to delay apoptosis of", "delay apoptosis of infected", "apoptosis of infected cells.", "of infected cells. the", "infected cells. the assembly", "cells. the assembly and", "the assembly and budding", "assembly and budding of", "and budding of rsv", "budding of rsv virions", "of rsv virions primarily", "rsv virions primarily occurs", "virions primarily occurs at", "primarily occurs at the", "occurs at the apical", "at the apical surface", "the apical surface of", "apical surface of ciliated", "surface of ciliated airway", "of ciliated airway epithelial", "ciliated airway epithelial cells", "airway epithelial cells where", "epithelial cells where viral", "cells where viral filaments", "where viral filaments containing", "viral filaments containing rnps", "filaments containing rnps form.", "containing rnps form. the", "rnps form. the budding", "form. the budding of", "the budding of rsv", "of rsv virions requires", "rsv virions requires interactions", "virions requires interactions between", "requires interactions between viral", "interactions between viral proteins", "viral proteins host", "proteins host cytoskeletal", "cytoskeletal proteins and", "proteins and membrane.", "and membrane. for review", "for review please", "review please refer", "please refer to shaikh", "refer to shaikh and", "to shaikh and crowe", "shaikh and crowe 2013", "crowe 2013 and", "2013 and battles", "and battles and mclellan", "battles and mclellan 2019.

              based", "and mclellan 2019.

              based on", "mclellan 2019.

              based on the", "2019.

              based on the findings", "on the findings that", "the findings that p", "that p m", "m and f", "and f proteins are", "f proteins are sufficient", "proteins are sufficient for", "are sufficient for formation", "sufficient for formation of", "for formation of viral\u2011like", "formation of viral\u2011like particles", "viral\u2011like particles vlps", "vlps p", "p protein particularly", "protein particularly its", "particularly its highly phosphorylated", "its highly phosphorylated serine/threonine\u2011rich", "highly phosphorylated serine/threonine\u2011rich region", "phosphorylated serine/threonine\u2011rich region between", "serine/threonine\u2011rich region between amino", "region between amino acids", "between amino acids 39", "amino acids 39 and", "acids 39 and 57", "39 and 57 that", "and 57 that likely", "57 that likely interacts", "that likely interacts with", "likely interacts with m", "interacts with m and/or", "with m and/or f", "m and/or f proteins", "f proteins may", "proteins may play", "may play an important", "play an important role", "an important role in", "important role in the", "role in the assembly", "the assembly meshram", "assembly meshram and", "meshram and oomens 2019", "and oomens 2019 .", "a mature virion of the", "mature virion of the respiratory", "virion of the respiratory syncytial", "of the respiratory syncytial virus", "virus rsv consists", "rsv consists of the", "consists of the ribonucleoprotein complex", "the ribonucleoprotein complex rnp", "complex rnp surrounded", "rnp surrounded by the", "surrounded by the protein matrix", "by the protein matrix and", "the protein matrix and a", "protein matrix and a lipid", "matrix and a lipid bilayer", "and a lipid bilayer envelope.", "a lipid bilayer envelope. the", "lipid bilayer envelope. the rnp", "bilayer envelope. the rnp is", "envelope. the rnp is composed", "the rnp is composed of", "rnp is composed of the", "is composed of the genomic", "composed of the genomic negative", "of the genomic negative sense", "the genomic negative sense single", "genomic negative sense single stranded", "single stranded ssrna", "ssrna that is tightly", "that is tightly associated with", "is tightly associated with the", "tightly associated with the n", "associated with the n protein", "the n protein nucleoprotein", "protein nucleoprotein and", "nucleoprotein and the rna", "and the rna dependent rna", "the rna dependent rna polymerase", "rna dependent rna polymerase complex", "rna polymerase complex rdrp", "polymerase complex rdrp .", "complex rdrp . the", "rdrp . the rdrp consists", ". the rdrp consists of", "the rdrp consists of the", "rdrp consists of the l", "consists of the l protein", "of the l protein subunit", "l protein subunit large", "protein subunit large polymerase", "subunit large polymerase subunit", "polymerase subunit the", "subunit the p", "p protein subunit phosphoprotein", "protein subunit phosphoprotein polymerase", "subunit phosphoprotein polymerase cofactor", "polymerase cofactor and", "cofactor and the", "and the m2 1 protein", "m2 1 protein which", "1 protein which acts", "protein which acts as", "which acts as a transcription", "acts as a transcription processivity", "as a transcription processivity factor.", "a transcription processivity factor. the", "transcription processivity factor. the matrix", "processivity factor. the matrix consists", "factor. the matrix consists of", "the matrix consists of the", "matrix consists of the m", "of the m matrix", "m matrix protein.", "matrix protein. the m2", "protein. the m2 1 protein", "the m2 1 protein serves", "m2 1 protein serves as", "1 protein serves as the", "protein serves as the bridge", "serves as the bridge between", "as the bridge between the", "the bridge between the rnp", "bridge between the rnp and", "between the rnp and the", "the rnp and the m", "rnp and the m protein.", "and the m protein. the", "the m protein. the matrix", "m protein. the matrix supports", "protein. the matrix supports the", "the matrix supports the viral", "matrix supports the viral envelope.", "supports the viral envelope. the", "the viral envelope. the viral", "viral envelope. the viral envelope", "envelope. the viral envelope contains", "the viral envelope contains three", "viral envelope contains three embedded", "envelope contains three embedded viral", "contains three embedded viral proteins:", "three embedded viral proteins: fusion", "embedded viral proteins: fusion protein", "proteins: fusion protein f", "f attachment protein", "g and a", "and a small hydrophobic protein", "small hydrophobic protein sh", "hydrophobic protein sh .", "protein sh . the", "sh . the m protein", ". the m protein associates", "the m protein associates with", "m protein associates with the", "protein associates with the cytoplasmic", "associates with the cytoplasmic domain", "with the cytoplasmic domain of", "the cytoplasmic domain of the", "cytoplasmic domain of the f", "domain of the f protein.", "of the f protein. the", "the f protein. the sh", "f protein. the sh protein", "protein. the sh protein forms", "the sh protein forms a", "sh protein forms a pentameric", "protein forms a pentameric ion", "forms a pentameric ion channel", "a pentameric ion channel in", "pentameric ion channel in the", "ion channel in the viral", "channel in the viral envelope", "in the viral envelope and", "the viral envelope and is", "viral envelope and is thought", "envelope and is thought to", "and is thought to delay", "is thought to delay apoptosis", "thought to delay apoptosis of", "to delay apoptosis of infected", "delay apoptosis of infected cells.", "apoptosis of infected cells. the", "of infected cells. the assembly", "infected cells. the assembly and", "cells. the assembly and budding", "the assembly and budding of", "assembly and budding of rsv", "and budding of rsv virions", "budding of rsv virions primarily", "of rsv virions primarily occurs", "rsv virions primarily occurs at", "virions primarily occurs at the", "primarily occurs at the apical", "occurs at the apical surface", "at the apical surface of", "the apical surface of ciliated", "apical surface of ciliated airway", "surface of ciliated airway epithelial", "of ciliated airway epithelial cells", "ciliated airway epithelial cells where", "airway epithelial cells where viral", "epithelial cells where viral filaments", "cells where viral filaments containing", "where viral filaments containing rnps", "viral filaments containing rnps form.", "filaments containing rnps form. the", "containing rnps form. the budding", "rnps form. the budding of", "form. the budding of rsv", "the budding of rsv virions", "budding of rsv virions requires", "of rsv virions requires interactions", "rsv virions requires interactions between", "virions requires interactions between viral", "requires interactions between viral proteins", "between viral proteins host", "viral proteins host cytoskeletal", "proteins host cytoskeletal proteins", "host cytoskeletal proteins and", "cytoskeletal proteins and membrane.", "proteins and membrane. for", "membrane. for review please", "for review please refer", "review please refer to", "please refer to shaikh and", "refer to shaikh and crowe", "to shaikh and crowe 2013", "and crowe 2013 and", "crowe 2013 and battles", "2013 and battles and", "and battles and mclellan 2019.

              based", "battles and mclellan 2019.

              based on", "and mclellan 2019.

              based on the", "mclellan 2019.

              based on the findings", "2019.

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              the", "to the urinary bladder.
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2014", "marcotte et al. 2014 .", "et al. 2014 . pax2", "2014 . pax2 pax8", "pax2 pax8 and", "pax8 and lhx1 are", "and lhx1 are expressed early", "lhx1 are expressed early during", "are expressed early during the", "expressed early during the formation", "early during the formation of", "during the formation of the", "the formation of the intermediate", "formation of the intermediate mesoderm.", "of the intermediate mesoderm. subsequently", "intermediate mesoderm. subsequently expression", "mesoderm. subsequently expression of", "subsequently expression of lhx1", "expression of lhx1 becomes restricted", "of lhx1 becomes restricted to", "lhx1 becomes restricted to the", "becomes restricted to the developing", "restricted to the developing renal", "to the developing renal progenitors", "the developing renal progenitors and", "developing renal progenitors and is", "renal progenitors and is maintained", "progenitors and is maintained by", "and is maintained by pax2", "is maintained by pax2 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              as the neural plate folds", "the neural plate folds to", "neural plate folds to form", "plate folds to form the", "folds to form the neural", "to form the neural tube", "the neural tube the", "neural tube the neural", "tube the neural plate", "the neural plate border contributes", "neural plate border contributes to", "plate border contributes to the", "border contributes to the olfactory", "to the olfactory lens", "olfactory lens and", "lens and hypophyseal placodes", "and hypophyseal placodes in the", "hypophyseal placodes in the anterior", "placodes in the anterior region", "in the anterior region and", "the anterior region and the", "anterior region and the neural", "region and the neural crest", "and the neural crest in", "the neural crest in the", "neural crest in the posterior", "crest in the posterior region", "the posterior region reviewed", "posterior region reviewed in", "region reviewed in singh", "reviewed in singh and groves", "in singh and groves 2016", "and groves 2016 koontz", "groves 2016 koontz et", "2016 koontz et al.", "koontz et al. 2023 .", "et al. 2023 . in", "al. 2023 . in addition", ". in addition the", "in addition the otic", "addition the otic placodes", "the otic placodes and cranial", "otic placodes and cranial sensory", "placodes and cranial sensory placodes", "and cranial sensory placodes arise", "cranial sensory placodes arise immediately", "sensory placodes arise immediately lateral", "placodes arise immediately lateral to", "arise immediately lateral to the", "immediately lateral to the neural", "lateral to the neural crest.", "to the neural crest. the", "the neural crest. the neural", "neural crest. the neural crest", "crest. the neural crest is", "the neural crest is a", "neural crest is a population", "crest is a population of", "is a population of migratory", "a population of migratory cells", "population of migratory cells located", "of migratory cells located dorsal", "migratory cells located dorsal to", "cells located dorsal to the", "located dorsal to the neural", "dorsal to the neural tube", "to the neural tube that", "the neural tube that is", "neural tube that is unique", "tube that is unique to", "that is unique to vertebrates", "unique to vertebrates reviewed", "to vertebrates reviewed in", "vertebrates reviewed in cheung", "reviewed in cheung et al.", "in cheung et al. 2019", "et al. 2019 and", "al. 2019 and gives", "2019 and gives rise", "and gives rise to several", "gives rise to several cell", "rise to several cell types", "several cell types including", "cell types including neurons", "types including neurons and", "including neurons and glia of", "neurons and glia of the", "and glia of the peripheral", "glia of the peripheral nervous", "of the peripheral nervous system", "peripheral nervous system osteoblasts", "nervous system osteoblasts and", "system osteoblasts and chondrocytes", "osteoblasts and chondrocytes of the", "and chondrocytes of the craniofacial", "chondrocytes of the craniofacial skeleton", "the craniofacial skeleton adrenal", "craniofacial skeleton adrenal medulla", "skeleton adrenal medulla cells", "adrenal medulla cells and", "medulla cells and melanocytes", "and melanocytes reviewed in", "melanocytes reviewed in kalcheim", "reviewed in kalcheim and kumar", "in kalcheim and kumar 2017", "kalcheim and kumar 2017 .", "and kumar 2017 . placodes", "kumar 2017 . placodes generate", "2017 . placodes generate the", ". placodes generate the olfactory", "placodes generate the olfactory epithelium", "the olfactory epithelium the", "olfactory epithelium the lens", "epithelium the lens of", "the lens of the eye", "of the eye the", "the eye the inner", "eye the inner ear", "the inner ear the", "inner ear the endocrine", "ear the endocrine adenohypophysis", "the endocrine adenohypophysis of the", "endocrine adenohypophysis of the pituitary", "adenohypophysis of the pituitary gland", "the pituitary gland and", "pituitary gland and some", "gland and some neurons", "and some neurons of the", "some neurons of the cranial", "neurons of the cranial sensory", "of the cranial sensory ganglia", "cranial sensory ganglia reviewed", "sensory ganglia reviewed in", "ganglia reviewed in alsina", "reviewed in alsina 2020 .
              the", "in alsina 2020 .
              the neural", "alsina 2020 .
              the neural plate", "2020 .
              the neural plate border", ".
              the neural plate border is", "neural plate border is specified", "plate border is specified by", "border is specified by a", "is specified by a combination", "specified by a combination of", "by a combination of transcription", "a combination of transcription factors", "combination of transcription factors including", "of transcription factors including gbx2", "factors including gbx2 tfap2a", "gbx2 tfap2a msx1", "tfap2a msx1 msx2", "msx1 msx2 zic1", "msx2 zic1 zic3", "zic1 zic3 dlx5/6", "zic3 dlx5/6 pax3", "dlx5/6 pax3 and", "pax3 and pax7. these", "and pax7. these factors may", "pax7. these factors may also", "these factors may also be", "factors may also be expressed", "may also be expressed in", "also be expressed in additional", "expressed in additional overlapping", "in additional overlapping regions.", "additional overlapping regions. for", "overlapping regions. for example zic1", "regions. for example zic1 is", "for example zic1 is expressed", "example zic1 is expressed in", "zic1 is expressed in the", "is expressed in the neural", "expressed in the neural plate", "in the neural plate border", "the neural plate border and", "neural plate border and more", "plate border and more medially", "border and more medially in", "and more medially in the", "more medially in the neural", "medially in the neural plate", "the neural plate where", "neural plate where it", "plate where it is", "where it is involved in", "it is involved in neural", "is involved in neural induction.", "involved in neural induction. tfap2a", "in neural induction. tfap2a is", "neural induction. tfap2a is expressed", "induction. tfap2a is expressed in", "tfap2a is expressed in the", "plate border and more laterally", "border and more laterally in", "and more laterally in the", "more laterally in the epidermis.", "laterally in the epidermis. thus", "in the epidermis. thus the", "the epidermis. thus the neural", "epidermis. thus the neural plate", "thus the neural plate border", "the neural plate border is", "neural plate border is defined", "plate border is defined by", "border is defined by a", "is defined by a combination", "defined by a combination of", "by a combination of factors", "a combination of factors rather", "combination of factors rather than", "of factors rather than by", "factors rather than by a", "rather than by a single", "than by a single factor", "a single factor reviewed", "single factor reviewed in", "factor reviewed in prasad", "reviewed in prasad et al.", "in prasad et al. 2019", "prasad et al. 2019 .
              the", "et al. 2019 .
              the order", "al. 2019 .
              the order of", "2019 .
              the order of expression", ".
              the order of expression of", "order of expression of neural", "of expression of neural plate", "expression of neural plate border", "of neural plate border specifiers", "neural plate border specifiers is", "plate border specifiers is not", "border specifiers is not completely", "specifiers is not completely characterized", "is not completely characterized in", "not completely characterized in humans.", "completely characterized in humans. in", "characterized in humans. in human", "in humans. in human embryonic", "humans. in human embryonic stem", "in human embryonic stem cells", "human embryonic stem cells differentiated", "embryonic stem cells differentiated in", "stem cells differentiated in vitro", "differentiated in vitro gbx2", "in vitro gbx2 is", "vitro gbx2 is expressed", "gbx2 is expressed broadly in", "is expressed broadly in the", "expressed broadly in the posterior", "broadly in the posterior ectoderm", "the posterior ectoderm then", "posterior ectoderm then tfap2a", "tfap2a pax3 pax7", "pax3 pax7 and", "pax7 and msx1 are", "and msx1 are expressed in", "msx1 are expressed in a", "are expressed in a neural", "expressed in a neural plate", "in a neural plate border", "a neural plate border state", "plate border state leung", "border state leung et", "state leung et al.", "leung et al. 2016 .", "et al. 2016 . the", "al. 2016 . the primacy", "2016 . the primacy of", ". the primacy of gbx2", "the primacy of gbx2 is", "primacy of gbx2 is also", "of gbx2 is also observed", "gbx2 is also observed in", "is also observed in xenopus", "also observed in xenopus embryos", "in xenopus embryos li", "xenopus embryos li et", "embryos li et al.", "li et al. 2009 .", "et al. 2009 . these", "al. 2009 . these genes", "2009 . these genes then", ". these genes then cross", "these genes then cross regulate", "genes then cross regulate each", "then cross regulate each other's", "cross regulate each other's expression", "regulate each other's expression to", "each other's expression to create", "other's expression to create a", "expression to create a self", "to create a self reinforcing", "create a self reinforcing module." ] }, { "record_id": "GLY_000594_1_2136", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9840373", "r hsa", "hsa 9840373", "r hsa 9840373" ] }, { "record_id": "GLY_000594_1_2136", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "cellular response", "response to", "to mitochondrial", "mitochondrial stress", "cellular response to", "response to mitochondrial", "to mitochondrial stress", "cellular response to mitochondrial", "response to mitochondrial stress", "cellular response to mitochondrial stress", "stress caused", "caused by", "by depolarization", "depolarization of", "of the", "the mitochondrial", "mitochondrial inner", "inner membrane", "inhibition of", "of proton", "proton flux", "flux across", "across the", "or insufficient", "insufficient protein", "protein import", "import capacity", "capacity caused", "by inhibition", "of atp", "atp synthase", "synthase or", "or iron", "iron deficiency", "deficiency is", "is communicated", "communicated to", "to the", "the cytosol", "cytosol and", "and nucleus", "resulting in", "in decreased", "decreased protein", "protein production", "production and", "and increased", "increased transcription", "transcription of", "of chaperones", "chaperones and", "and metabolic", "metabolic genes", "genes among", "among others.", "others. this", "this pathway", "pathway is", "is known", "known as", "as the", "stress response", "response and", "and is", "is a", "a part", "part of", "of mitochondrial", "mitochondrial signaling", "signaling and", "and the", "the integrated", "integrated stress", "reviewed in", "in eckl", "eckl et", "et al.", "al. 2021", "picard and", "and shirihai", "shirihai 2022", "lu et", "al. 2022", "liu and", "and birsoy", "birsoy 2023", "2023 .", ". the", "response participates", "participates in", "in adapting", "adapting cells", "cells to", "to harsher", "harsher environments", "environments and", "plays a", "a role", "role in", "in tumor", "tumor progression", "progression and", "and metastasis", "in lee", "lee et", "2022 .
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"mitochondrial stress caused by depolarization", "stress caused by depolarization of", "caused by depolarization of the", "by depolarization of the mitochondrial", "depolarization of the mitochondrial inner", "of the mitochondrial inner membrane", "mitochondrial inner membrane inhibition", "inner membrane inhibition of", "membrane inhibition of proton", "inhibition of proton flux across", "of proton flux across the", "proton flux across the mitochondrial", "flux across the mitochondrial inner", "across the mitochondrial inner membrane", "mitochondrial inner membrane or", "inner membrane or insufficient", "membrane or insufficient protein", "or insufficient protein import capacity", "insufficient protein import capacity caused", "protein import capacity caused by", "import capacity caused by inhibition", "capacity caused by inhibition of", "caused by inhibition of atp", "by inhibition of atp synthase", "inhibition of atp synthase or", "of atp synthase or iron", "atp synthase or iron deficiency", "synthase or iron deficiency is", "or iron deficiency is communicated", "iron deficiency is communicated to", "deficiency is communicated to the", "is communicated to the cytosol", "communicated to the cytosol and", "to the cytosol and nucleus", "cytosol and nucleus resulting", "and nucleus resulting in", "nucleus resulting in decreased", "resulting in decreased protein production", "in decreased protein production and", "decreased protein production and increased", "protein production and increased transcription", "production and increased transcription of", "and increased transcription of chaperones", "increased transcription of chaperones and", "transcription of chaperones and metabolic", "of chaperones and metabolic genes", "chaperones and metabolic genes among", "and metabolic genes among others.", "metabolic genes among others. this", "genes among others. this pathway", "among others. this pathway is", "others. this pathway is known", "this pathway is known as", "pathway is known as the", "is known as the mitochondrial", "known as the mitochondrial stress", "as the mitochondrial stress response", "the mitochondrial stress response and", "mitochondrial stress response and is", "stress response and is a", "response and is a part", "and is a part of", "is a part of mitochondrial", "a part of mitochondrial signaling", "part of mitochondrial signaling and", "of mitochondrial signaling and the", "mitochondrial signaling and the integrated", "signaling and the integrated stress", "and the integrated stress response", "integrated stress response reviewed", "stress response reviewed in", "response reviewed in eckl", "reviewed in eckl et al.", "in eckl et al. 2021", "et al. 2021 picard", "al. 2021 picard and", "2021 picard and shirihai", "and shirihai 2022 lu", "shirihai 2022 lu et", "2022 lu et al.", "et al. 2022 liu", "al. 2022 liu and", "2022 liu and birsoy", "liu and birsoy 2023 .", "and birsoy 2023 . the", "birsoy 2023 . the mitochondrial", "2023 . the mitochondrial stress", ". the mitochondrial stress response", "the mitochondrial stress response participates", "mitochondrial stress response participates in", "stress response participates in adapting", "response participates in adapting cells", "participates in adapting cells to", "in adapting cells to harsher", "adapting cells to harsher environments", "cells to harsher environments and", "harsher environments and hence", "and hence plays", "hence plays a role", "plays a role in tumor", "a role in tumor progression", "role in tumor progression and", "in tumor progression and metastasis", "progression and metastasis reviewed", "and metastasis reviewed in", "metastasis reviewed in lee", "reviewed in lee et al.", "in lee et al. 2022", "lee et al. 2022 .
              in", "et al. 2022 .
              in unstressed", "al. 2022 .
              in unstressed mitochondria", ".
              in unstressed mitochondria dele1", "unstressed mitochondria dele1 is", "mitochondria dele1 is constitutively", "dele1 is constitutively imported into", "is constitutively imported into the", "constitutively imported into the mitochondrial", "imported into the mitochondrial matrix", "into the mitochondrial matrix and", "the mitochondrial matrix and degraded", "mitochondrial matrix and degraded by", "matrix and degraded by the", "and degraded by the lonp1", "degraded by the lonp1 atp", "by the lonp1 atp dependent", "the lonp1 atp dependent protease", "atp dependent protease fessler", "dependent protease fessler et", "protease fessler et al.", "et al. 2022 sekine", "al. 2022 sekine et", "2022 sekine et al.", "sekine et al. 2023 .", "et al. 2023 . mitochondrial", "al. 2023 . mitochondrial stress", "2023 . mitochondrial stress inhibits", ". mitochondrial stress inhibits the", "mitochondrial stress inhibits the complete", "stress inhibits the complete transit", "inhibits the complete transit of", "the complete transit of dele1", "complete transit of dele1 into", "transit of dele1 into the", "of dele1 into the matrix", "dele1 into the matrix and", "into the matrix and activates", "the matrix and activates the", "matrix and activates the inner", "and activates the inner membrane", "activates the inner membrane protease", "the inner membrane protease oma1", "inner membrane protease oma1 by", "membrane protease oma1 by self", "protease oma1 by self cleavage", "by self cleavage fessler", "self cleavage fessler et", "cleavage fessler et al.", "et al. 2023 inferred", "al. 2023 inferred from", "2023 inferred from the", "inferred from the mouse oma1", "from the mouse oma1 homolog", "the mouse oma1 homolog in", "mouse oma1 homolog in baker", "oma1 homolog in baker et", "homolog in baker et al.", "in baker et al. 2014", "et al. 2014 zhang", "al. 2014 zhang et", "2014 zhang et al.", "zhang et al. 2014 .", "et al. 2014 . activated", "al. 2014 . activated oma1", "2014 . activated oma1 cleaves", ". activated oma1 cleaves the", "activated oma1 cleaves the n", "oma1 cleaves the n terminal", "cleaves the n terminal region", "the n terminal region of", "n terminal region of dele1", "terminal region of dele1 on", "region of dele1 on the", "of dele1 on the outer", "dele1 on the outer face", "on the outer face of", "the outer face of the", "outer face of the inner", "face of the inner membrane", "of the inner membrane as", "the inner membrane as dele1", "inner membrane as dele1 is", "membrane as dele1 is unable", "as dele1 is unable to", "dele1 is unable to fully", "is unable to fully cross", "unable to fully cross the", "to fully cross the inner", "fully cross the inner membrane", "the inner membrane fessler", "inner membrane fessler et", "membrane fessler et al.", "et al. 2020 guo", "al. 2020 guo et", "2020 guo et al.", "et al. 2020 fessler", "al. 2020 fessler et", "2020 fessler et al.", "fessler et al. 2022 .", "et al. 2022 . the", "al. 2022 . the resulting", "2022 . the resulting c", ". the resulting c terminal", "the resulting c terminal fragment", "resulting c terminal fragment of", "c terminal fragment of dele1", "terminal fragment of dele1 egresses", "fragment of dele1 egresses from", "of dele1 egresses from the", "dele1 egresses from the intermembrane", "egresses from the intermembrane space", "from the intermembrane space to", "the intermembrane space to the", "intermembrane space to the cytosol", "space to the cytosol where", "to the cytosol where it", "the cytosol where it oligomerizes", "cytosol where it oligomerizes to", "where it oligomerizes to form", "it oligomerizes to form an", "oligomerizes to form an octamer", "form an octamer yang", "an octamer yang et", "octamer yang et al.", "et al. 2023 which", "al. 2023 which binds", "2023 which binds and", "which binds and activates eif2ak1", "and activates eif2ak1 a", "activates eif2ak1 a constituent", "eif2ak1 a constituent kinase", "a constituent kinase of the", "constituent kinase of the integrated", "kinase of the integrated stress", "of the integrated stress response", "the integrated stress response that", "integrated stress response that phosphorylates", "stress response that phosphorylates eif2s1", "that phosphorylates eif2s1 the", "phosphorylates eif2s1 the alpha", "eif2s1 the alpha subunit", "the alpha subunit of the", "alpha subunit of the eukaryotic", "subunit of the eukaryotic translation", "of the eukaryotic translation initiation", "the eukaryotic translation initiation factor", "eukaryotic translation initiation factor 2", "initiation factor 2 eif2", "eif2 fessler et", "et al. 2020 cheng", "al. 2020 cheng et", "2020 cheng et al.", "cheng et al. 2022 .", "et al. 2022 . phosphorylation", "al. 2022 . phosphorylation of", "2022 . phosphorylation of eif2s1", ". phosphorylation of eif2s1 inhibits", "phosphorylation of eif2s1 inhibits general", "of eif2s1 inhibits general translation", "eif2s1 inhibits general translation but", "inhibits general translation but increases", "general translation but increases translation", "translation but increases translation of", "but increases translation of specific", "increases translation of specific mrnas", "translation of specific mrnas that", "of specific mrnas that possess", "specific mrnas that possess upstream", "mrnas that possess upstream open", "that possess upstream open reading", "possess upstream open reading frames", "open reading frames reviewed", "reading frames reviewed in", "frames reviewed in wek", "reviewed in wek 2018 .", "in wek 2018 . among", "wek 2018 . among these", "2018 . among these mrnas", ". among these mrnas are", "among these mrnas are the", "these mrnas are the transcription", "mrnas are the transcription factors", "are the transcription factors ddit3", "transcription factors ddit3 chop", "and atf5 which activate", "atf5 which activate expression", "which activate expression of chaperone", "activate expression of chaperone genes", "expression of chaperone genes among", "of chaperone genes among others." ] }, { "record_id": "GLY_000594_1_2137", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9845619", "r hsa", "hsa 9845619", "r hsa 9845619" ] }, { "record_id": "GLY_000594_1_2137", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "enhanced cleavage", "cleavage of", "of vwf", "vwf variant", "variant by", "by adamts13", "enhanced cleavage of", "cleavage of vwf", "of vwf variant", "vwf variant by", "variant by adamts13", "enhanced cleavage of vwf", "cleavage of vwf variant", "of vwf variant by", "vwf variant by adamts13", "enhanced cleavage of vwf variant", "cleavage of vwf variant by", "of vwf variant by adamts13", "under normal", "normal physiological", "physiological conditions", "a disintegrin", "disintegrin and", "and metalloproteinase", "metalloproteinase with", "with thrombospondin", "thrombospondin type", "type 1", "1 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"GLY_000594_1_2138", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9845620", "r hsa", "hsa 9845620", "r hsa 9845620" ] }, { "record_id": "GLY_000594_1_2138", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "enhanced binding", "binding of", "of gp1ba", "gp1ba variant", "variant to", "to vwf", "vwf multimer:collagen", "enhanced binding of", "binding of gp1ba", "of gp1ba variant", "gp1ba variant to", "variant to vwf", "to vwf multimer:collagen", "enhanced binding of gp1ba", "binding of gp1ba variant", "of gp1ba variant to", "gp1ba variant to vwf", "variant to vwf multimer:collagen", "enhanced binding of gp1ba variant", "binding of gp1ba variant to", "of gp1ba variant to vwf", "gp1ba variant to vwf multimer:collagen", "the reactome", "reactome event", "event describes", "describes gain", "gain of", "of function", "function variants", "variants of", "of glycoprotein", "glycoprotein ib", "ib 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"has been associated with greater", "been associated with greater risk", "associated with greater risk of", "with greater risk of metastasis", "risk of metastasis mueller", "of metastasis mueller tidow", "metastasis mueller tidow et", "tidow et al 2005", "al 2005 roll", "2005 roll and reuther", "reuther 2012 . more", ". more recently a", "more recently a novel", "recently a novel clip1", "a novel clip1 ltk fusion", "novel clip1 ltk fusion protein", "clip1 ltk fusion protein has", "ltk fusion protein has been", "fusion protein has been identified", "protein has been identified in", "has been identified in a", "been identified in a small", "identified in a small proportion", "in a small proportion of", "a small proportion of nsclc", "small proportion of nsclc cases", "of nsclc cases izumi", "nsclc cases izumi et", "cases izumi et al", "izumi et al 2021", "et al 2021 ." ] }, { "record_id": "GLY_000594_1_2146", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9842663", "r hsa", "hsa 9842663", "r hsa 9842663" ] }, { "record_id": "GLY_000594_1_2146", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "signaling by", "by ltk", "signaling by ltk", "leukocyte tyrosine", "tyrosine kinase", "is a", "a transmembrane", "transmembrane receptor", "receptor tyrosine", "kinase that", "that is", "a member", "member of", "of the", "the insulin", "insulin growth", "growth factor", "factor receptor", "receptor superfamily.", "superfamily. ltk", "ltk is", "is most", "most closely", "closely related", "related to", "to the", "the alk", "alk receptor", "and may", "may have", "have originated", "originated as", "as a", "a result", "result of", "of a", "a duplication", "duplication event", "event of", "alk gene", "krowelski and", "and dalla", "dalla favera", "dornburg et", "et al", "2021 .", ". the", "the extracellular", "extracellular domains", "domains of", "of alk", "alk and", "and ltk", "ltk are", "are 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to", "the er to the", "er to the golgi", "to the golgi has", "the golgi has also", "golgi has also been", "has also been proposed", "been proposed and", "proposed and one", "and one study suggests", "one study suggests that", "study suggests that ltk", "suggests that ltk may", "that ltk may actually", "ltk may actually bean", "may actually bean er", "actually bean er resident", "bean er resident protein", "resident protein farhan", "protein farhan et", "et al 2010", "2010 centonze et", "et al 2019", "al 2019 .", "2019 . more recently", "more recently fusions", "recently fusions of", "fusions of ltk have", "of ltk have been", "ltk have been identified", "have been identified in", "been identified in non", "identified in non small", "in non small cell", "non small cell lung", "small cell lung cancer", "lung cancer izumi", "cancer izumi et", "leukocyte tyrosine kinase ltk", "kinase ltk is", "ltk is a transmembrane", "is a transmembrane receptor tyrosine", "a transmembrane receptor 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duplication event of the", "duplication event of the alk", "event of the alk gene", "the alk gene krowelski", "alk gene krowelski and", "gene krowelski and dalla", "and dalla favera 1991", "favera 1991 dornburg", "1991 dornburg et al", "dornburg et al 2021", "et al 2021 .", "al 2021 . the", "2021 . the extracellular domains", ". the extracellular domains of", "the extracellular domains of alk", "extracellular domains of alk and", "domains of alk and ltk", "of alk and ltk are", "alk and ltk are characterized", "and ltk are characterized by", "ltk are characterized by a", "are characterized by a membrane", "characterized by a membrane proximal", "by a membrane proximal egf", "a membrane proximal egf like", "proximal egf like egfl", "like egfl module", "egfl module a", "module a unique 250", "a unique 250 amino acid", "unique 250 amino acid glycine", "250 amino acid glycine rich", "acid glycine rich gr", "rich gr domain", "domain that in drosophila", "in drosophila is essential", 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"1997 demunck et al", "demunck et al 2021", "al 2021 . these", "2021 . these differences in", ". these differences in ecd", "these differences in ecd may", "differences in ecd may contribute", "in ecd may contribute to", "ecd may contribute to differences", "may contribute to differences in", "contribute to differences in the", "to differences in the ligand", "differences in the ligand binding", "in the ligand binding affinities", "the ligand binding affinities of", "ligand binding affinities of the", "binding affinities of the two", "affinities of the two receptors.
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              ltk is activated by the", "is activated by the binding", "activated by the binding of", "by the binding of cytokines", "the binding of cytokines alkal1", "binding of cytokines alkal1 and", "of cytokines alkal1 and alkal2", "cytokines alkal1 and alkal2 to", "alkal1 and alkal2 to the", "and alkal2 to the ecd", "to the ecd zhang", "the ecd zhang et", "ecd zhang et al", "zhang et al 2014", "al 2014 reshetnyak", "2014 reshetnyak et al", "reshetnyak et al 2015", "al 2015 reshetnyak", "2015 reshetnyak et al", "reshetnyak et al 2018", "et al 2018 .", "al 2018 . ligand", "2018 . ligand binding induces", ". ligand binding induces trans", "ligand binding induces trans autophosphorylation", "binding induces trans autophosphorylation in", "induces trans autophosphorylation in the", "trans autophosphorylation in the intracellular", "autophosphorylation in the intracellular domain", "in the intracellular domain of", "the intracellular domain of the", "intracellular domain of the receptor", "domain of the receptor and", "of the receptor and promotes", "the receptor and promotes the", "receptor and promotes the interaction", "and promotes the interaction and", "promotes the interaction and activation", "the interaction and activation of", "interaction and activation of downstream", "and activation of downstream signaling", "activation of downstream signaling molecules", "of downstream signaling molecules such", "downstream signaling molecules such as", "signaling molecules such as shc", "such as shc irs1", "shc irs1 cbl", "irs1 cbl and pi3k", "cbl and pi3k with the", "and pi3k with the phosphorylated", "pi3k with the phosphorylated receptor", "the phosphorylated receptor kozutsumi", "phosphorylated receptor kozutsumi et", "receptor kozutsumi et al", "kozutsumi et al 1994", "al 1994 honda", "1994 honda et al", "honda et al 1994", "al 1994 ueno", "1994 ueno et al", "ueno et al 1995", "al 1995 ueno", "1995 ueno et al", "ueno et al 1996", "al 1996 ueno", "1996 ueno et al", "ueno et al 1997", "al 1997 li", "1997 li et al", "li et al 2004", "al 2004 yamada", "2004 yamada et al", "yamada et al 2008", "et al 2008 .", "al 2008 . note", "2008 . note however that", ". note however that much", "note however that much of", "however that much of the", "that much of the early", "much of the early functional", "of the early functional studies", "the early functional studies on", "early functional studies on ltk", "functional studies on ltk were", "studies on ltk were conducted", "on ltk were conducted before", "ltk were conducted before the", "were conducted before the identification", "conducted before the identification of", "before the identification of alkal1", "the identification of alkal1 and", "identification of alkal1 and 2", "of alkal1 and 2 as", "alkal1 and 2 as physiological", "and 2 as physiological ligands.", "2 as physiological ligands. in", "as physiological ligands. in consequence", "ligands. in consequence many", "in consequence many of", "consequence many of these", "many of these studies were", "of these studies were carried", "these studies were carried out", "studies were carried out using", "were carried out using chimeric", "carried out using chimeric receptors", "out using chimeric receptors consisting", "using chimeric receptors consisting of", "chimeric receptors consisting of the", "receptors consisting of the ecd", "of the ecd and", "the ecd and stimulating", "ecd and stimulating ligands", "and stimulating ligands of", "stimulating ligands of well", "ligands of well characterized", "of well characterized receptors fused", "well characterized receptors fused to", "characterized receptors fused to the", "receptors fused to the intracellular", "fused to the intracellular domain", "to the intracellular domain of", "the intracellular domain of ltk.
              the", "intracellular domain of ltk.
              the exact", "domain of ltk.
              the exact role", "of ltk.
              the exact role of", "ltk.
              the exact role of ltk", "exact role of ltk signaling", "role of ltk signaling is", "of ltk signaling is likewise", "ltk signaling is likewise not", "signaling is likewise not fully", "is likewise not fully elucidated.", "likewise not fully elucidated. expression", "not fully elucidated. expression of", "fully elucidated. expression of the", "elucidated. expression of the chimeric", "expression of the chimeric ltk", "of the chimeric ltk proteins", "the chimeric ltk proteins described", "chimeric ltk proteins described above", "ltk proteins described above promotes", "proteins described above promotes neurite", "described above promotes neurite outgrowth", "above promotes neurite outgrowth and", "promotes neurite outgrowth and cell", "neurite outgrowth and cell survival", "and cell survival ueno", "cell survival ueno et", "survival ueno et al", "al 1997 yamada", "1997 yamada et al", "al 2008 . a", "2008 . a role for", ". a role for ltk", "a role for ltk in", "role for ltk in the", "for ltk in the regulation", "ltk in the regulation of", "in the regulation of transport", "the regulation of transport from", "regulation of transport from the", "of transport from the er", "transport from the er to", "from the er to the", "the er to the golgi", "er to the golgi has", "to the golgi has also", "the golgi has also been", "golgi has also been proposed", "also been proposed and", "been proposed and one", "proposed and one study", "and one study suggests that", "one study suggests that ltk", "study suggests that ltk may", "suggests that ltk may actually", "that ltk may actually bean", "ltk may actually bean er", "may actually bean er resident", "actually bean er resident protein", "er resident protein farhan", "resident protein farhan et", "protein farhan et al", "farhan et al 2010", "al 2010 centonze", "2010 centonze et al", "centonze et al 2019", "et al 2019 .", "al 2019 . more", ". more recently fusions", "more recently fusions of", "recently fusions of ltk", 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              mutations", "2020

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              mutations", "al 2020

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              " ] }, { "record_id": "GLY_000594_1_2154", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9918438", "r hsa", "hsa 9918438", "r hsa 9918438" ] }, { "record_id": "GLY_000594_1_2154", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective visual", "visual phototransduction", "phototransduction due", "due to", "to rdh5", "rdh5 loss", "loss of", "of function", "defective visual phototransduction", "visual phototransduction due", "phototransduction due to", "due to rdh5", "to rdh5 loss", "rdh5 loss of", "loss of function", "defective visual phototransduction due", "visual phototransduction due to", "phototransduction due to rdh5", "due to rdh5 loss", "to rdh5 loss of", "rdh5 loss of function", "defective visual phototransduction due to", "visual phototransduction due to rdh5", "phototransduction due to rdh5 loss", "due to rdh5 loss of", "to rdh5 loss of function", "11 cis", "cis 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"phraselist": [ "regulation of", "of endogenous", "endogenous retroelements", "retroelements by", "by piwi", "piwi interacting", "interacting rnas", "regulation of endogenous", "of endogenous retroelements", "endogenous retroelements by", "retroelements by piwi", "by piwi interacting", "piwi interacting rnas", "rnas pirnas", "regulation of endogenous retroelements", "of endogenous retroelements by", "endogenous retroelements by piwi", "retroelements by piwi interacting", "by piwi interacting rnas", "interacting rnas pirnas", "regulation of endogenous retroelements by", "of endogenous retroelements by piwi", "endogenous retroelements by piwi interacting", "retroelements by piwi interacting rnas", "piwi interacting rnas pirnas", "are short", "short rnas", "rnas of", "of 24", "24 31", "31 nucleotides", "nucleotides that", "that are", "are produced", "produced by", "by cleavage", "cleavage of", "of longer", "longer rnas", "rnas and", "and amplification", "amplification by", "by a", "a \\ping", "\\ping pong\\", "pong\\ mechanism", "mechanism involving", "involving rounds", "rounds of", "of strand", "strand hybridization", "hybridization and", "and cleavage", "reviewed in", "in sun", "sun et", "et al.", "al. 2022", "2022 .", ". the", "the pirnas", "pirnas are", "are loaded", "loaded onto", "onto piwi", "piwi proteins", "are then", "then guided", "guided by", "by base", "base pairing", "pairing of", "of the", "pirnas to", "to nascent", "nascent and", "and mature", "mature transcripts", "where the", "the piwi:pirna", "piwi:pirna complexes", "complexes initiate", "initiate transcriptional", "transcriptional and", "and post", "post transcriptional", "transcriptional silencing", "in czech", "czech et", "al. 2018", "onishi et", "al. 2021", "wang et", "al. 2023", "2023 .
              in", ".
              in mice", "sources of", "of pirnas", "pirnas include", "include transposon", "transposon rnas", "long non", "non coding", "coding rnas", "exon transcripts", "and rnas", "rnas from", "from unannotated", "unannotated regions", "regions of", "the genome", "aravin et", "al. 2007", "2008 .", ". two", "two populations", "populations of", "are observed", "observed during", "during mouse", "mouse development:", "development: pre", "pre pachytene", "pachytene pirnas", "pirnas and", "and pachytene", "al. 2008", "gan et", "al. 2011", "2011 .", ". pre", "are present", "present prenatally", "prenatally in", "in prospermatogonial", "prospermatogonial cells", "cells and", "and postnatally", "postnatally in", "in spermatogonial", "spermatogonial cells.", "cells. pachytene", "present in", "in more", "more mature", "mature postnatal", "postnatal spermatocytes", "spermatocytes and", "and spermatids.", "spermatids. the", "pirnas derived", "derived from", "from retroelements", "retroelements comprise", "comprise about", "about half", "or less", "the total", "total pre", "and the", "the portion", "portion falls", "falls sharply", "sharply from", "from pre", "pachytene to", "to pachytene", "2011 .
              in", "piwil2 gene", "is first", "first detected", "detected in", "in primordial", "primordial germ", "germ cells", "cells that", "that have", "have reached", "reached the", "the genital", "genital ridge", "ridge and", "and expression", "expression persists", "persists through", "through meiosis", "meiosis in", "in adults.", "adults. piwil4", "piwil4 gene", "is present", "in mouse", "mouse germ", "cells during", "during de", "de novo", "novo dna", "dna methylation", "methylation shortly", "shortly before", "before and", "and after", "after birth.", "birth. piwil1", "piwil1 gene", "present during", "during later", "later stages", "stages of", "of meiosis", "meiosis after", "after birth", ". piwil4", "piwil4 and", "and piwil2", "piwil2 participate", "participate in", "in re", "re methylation", "methylation of", "genome in", "and consequent", "consequent repression", "repression of", "of transposable", "transposable elements", "carmell et", "kuramochi miyagawa", "miyagawa et", "zoch et", "al. 2020", "2020 .", ". in", "in mice", "pirnas bound", "bound by", "by piwil4", "piwil4 bind", "bind nascent", "nascent transcripts", "transcripts of", "elements and", "and connects", "connects to", "to the", "the de", "methylation machinery", "machinery via", "via spocd1", "spocd1 and", "and c19orf84", "c19orf84 to", "to direct", "direct dna", "methylation to", "the transposable", "2024 .", ". mutations", "mutations in", "in spocd1", "spocd1 are", "are associated", "associated with", "with infertility", "infertility in", "in men", "al. 2024", "are short rnas", "short rnas of", "rnas of 24", "of 24 31", "24 31 nucleotides", "31 nucleotides that", "nucleotides that are", "that are produced", "are produced by", "produced by cleavage", "by cleavage of", "cleavage of longer", "of longer rnas", "longer rnas and", "rnas and amplification", "and amplification by", "amplification by a", "by a \\ping", "a \\ping pong\\", "\\ping pong\\ mechanism", "pong\\ mechanism involving", "mechanism involving rounds", "involving rounds of", "rounds of strand", "of strand hybridization", "strand hybridization and", "hybridization and cleavage", "cleavage reviewed", "reviewed in sun", "in sun et", "sun et al.", "et al. 2022", "al. 2022 .", "2022 . the", ". the pirnas", "the pirnas are", "pirnas are loaded", "are loaded onto", "loaded onto piwi", "onto piwi proteins", "proteins piwil1", "piwil1 piwil2", "piwil2 piwil4", "piwil4 that", "that are then", "are then guided", "then guided by", "guided by base", "by base pairing", "base pairing of", "pairing of the", "of the pirnas", "the pirnas to", "pirnas to nascent", "to nascent and", "nascent and mature", "and mature transcripts", "transcripts where", "where the piwi:pirna", "the piwi:pirna complexes", "piwi:pirna complexes initiate", "complexes initiate transcriptional", "initiate transcriptional and", "transcriptional and post", "and post transcriptional", "post transcriptional silencing", "silencing respectively", "respectively reviewed", "reviewed in czech", "in czech et", "czech et al.", "et al. 2018", "2018 onishi", "onishi et al.", "et al. 2021", "2021 wang", "wang et al.", "et al. 2023", "al. 2023 .
              in", "2023 .
              in mice", "mice sources", "sources of pirnas", "of pirnas include", "pirnas include transposon", "include transposon rnas", "rnas long", "long non coding", "non coding rnas", "rnas exon", "transcripts and", "and rnas from", "rnas from unannotated", "from unannotated regions", "unannotated regions of", "regions of the", "of the genome", "genome aravin", "aravin et al.", "et al. 2007", "2007 2008", "2008 . two", ". two populations", "two populations of", "populations of pirnas", "of pirnas are", "pirnas are observed", "are observed during", "observed during mouse", "during mouse development:", "mouse development: pre", "development: pre pachytene", "pre pachytene pirnas", "pachytene pirnas and", "pirnas and pachytene", "and pachytene pirnas", "pirnas aravin", "et al. 2008", "2008 gan", "gan et al.", "et al. 2011", "al. 2011 .", "2011 . pre", ". pre pachytene", "pachytene pirnas are", "pirnas are present", "are present prenatally", "present prenatally in", "prenatally in prospermatogonial", "in prospermatogonial cells", "prospermatogonial cells and", "cells and postnatally", "and postnatally in", "postnatally in spermatogonial", "in spermatogonial cells.", "spermatogonial cells. pachytene", "cells. pachytene pirnas", "are present in", "present in more", "in more mature", "more mature postnatal", "mature postnatal spermatocytes", "postnatal spermatocytes and", "spermatocytes and spermatids.", "and spermatids. the", "spermatids. the pirnas", "the pirnas derived", "pirnas derived from", "derived from retroelements", "from retroelements comprise", "retroelements comprise about", "comprise about half", "half aravin", "2008 or", "less gan", "2011 of", "of the total", "the total pre", "total pre pachytene", "pirnas and the", "and the portion", "the portion falls", "portion falls sharply", "falls sharply from", "sharply from pre", "from pre pachytene", "pre pachytene to", "pachytene to pachytene", "pachytene gan", "al. 2011 .
              in", "2011 .
              in mice", "mice piwil2", "piwil2 mili", "mili piwil2", "gene is", "is first detected", "first detected in", "detected in primordial", "in primordial germ", "primordial germ cells", "germ cells that", "cells that have", "that have reached", "have reached the", "reached the genital", "the genital ridge", "genital ridge and", "ridge and expression", "and expression persists", "expression persists through", "persists through meiosis", "through meiosis in", "meiosis in adults.", "in adults. piwil4", "piwil4 miwi2", "miwi2 piwil4", "is present in", "present in mouse", "in mouse germ", "mouse germ cells", "germ cells during", "cells during de", "during de novo", "de novo dna", "novo dna methylation", "dna methylation shortly", "methylation shortly before", "shortly before and", "before and after", "and after birth.", "after birth. piwil1", "piwil1 miwi", "miwi piwil1", "is present during", "present during later", "during later stages", "later stages of", "stages of meiosis", "of meiosis after", "meiosis after birth", "birth aravin", "al. 2008 .", "2008 . piwil4", ". piwil4 and", "piwil4 and piwil2", "and piwil2 participate", "piwil2 participate in", "participate in re", "in re methylation", "re methylation of", "methylation of the", "the genome in", "genome in mouse", "germ cells and", "cells and consequent", "and consequent repression", "consequent repression of", "repression of transposable", "of transposable elements", "elements carmell", "carmell et al.", "2007 aravin", "2008 kuramochi", "kuramochi miyagawa et", "miyagawa et al.", "2008 zoch", "zoch et al.", "et al. 2020", "al. 2020 .", "2020 . in", ". in mice", "mice the", "the pirnas bound", "pirnas bound by", "bound by piwil4", "by piwil4 bind", "piwil4 bind nascent", "bind nascent transcripts", "nascent transcripts of", "transcripts of transposable", "transposable elements and", "elements and connects", "and connects to", "connects to the", "to the de", "the de novo", "dna methylation machinery", "methylation machinery via", "machinery via spocd1", "via spocd1 and", "spocd1 and c19orf84", "and c19orf84 to", "c19orf84 to direct", "to direct dna", "direct dna methylation", "dna methylation to", "methylation to the", "to the transposable", "the transposable elements", "elements zoch", "2020 2024", "2024 . mutations", ". mutations in", "mutations in spocd1", "in spocd1 are", "spocd1 are associated", "are associated with", "associated with infertility", "with infertility in", "infertility in men", "men zoch", "et al. 2024", "pirnas are short", "are short rnas of", "short rnas of 24", "rnas of 24 31", "of 24 31 nucleotides", "24 31 nucleotides that", "31 nucleotides that are", "nucleotides that are produced", "that are produced by", "are produced by cleavage", "produced by cleavage of", "by cleavage of longer", "cleavage of longer rnas", "of longer rnas and", "longer rnas and amplification", "rnas and amplification by", "and amplification by a", "amplification by a \\ping", "by a \\ping pong\\", "a \\ping pong\\ mechanism", "\\ping pong\\ mechanism involving", "pong\\ mechanism involving rounds", "mechanism involving rounds of", "involving rounds of strand", "rounds of strand hybridization", "of strand hybridization and", "strand hybridization and cleavage", "and cleavage reviewed", "cleavage reviewed in", "reviewed in sun et", "in sun et al.", "sun et al. 2022", "et al. 2022 .", "al. 2022 . the", "2022 . the pirnas", ". the pirnas are", "the pirnas are loaded", "pirnas are loaded onto", "are loaded onto piwi", "loaded onto piwi proteins", "piwi proteins piwil1", "piwil4 that are", "that are then guided", "are then guided by", "then guided by base", "guided by base pairing", "by base pairing of", "base pairing of the", "pairing of the pirnas", "of the pirnas to", "the pirnas to nascent", "pirnas to nascent and", "to nascent and mature", "nascent and mature transcripts", "mature transcripts where", "transcripts where the", "where the piwi:pirna complexes", "the piwi:pirna complexes initiate", "piwi:pirna complexes initiate transcriptional", "complexes initiate transcriptional and", "initiate transcriptional and post", "transcriptional and post transcriptional", "and post transcriptional silencing", "transcriptional silencing respectively", "respectively reviewed in", "reviewed in czech et", "in czech et al.", "czech et al. 2018", "al. 2018 onishi", "2018 onishi et", "onishi et al. 2021", "al. 2021 wang", "2021 wang et", "wang et al. 2023", "et al. 2023 .
              in", "al. 2023 .
              in mice", ".
              in mice sources", "mice sources of", "sources of pirnas include", "of pirnas include transposon", "pirnas include transposon rnas", "transposon rnas long", "rnas long non", "long non coding rnas", "coding rnas exon", "rnas exon transcripts", "exon transcripts and", "transcripts and rnas", "and rnas from unannotated", "rnas from unannotated regions", "from unannotated regions of", "unannotated regions of the", "regions of the genome", "the genome aravin", "genome aravin et", "aravin et al. 2007", "al. 2007 2008", "2007 2008 .", "2008 . two populations", ". two populations of", "two populations of pirnas", "populations of pirnas are", "of pirnas are observed", "pirnas are observed during", "are observed during mouse", "observed during mouse development:", "during mouse development: pre", "mouse development: pre pachytene", "development: pre pachytene pirnas", "pre pachytene pirnas and", "pachytene pirnas and pachytene", "pirnas and pachytene pirnas", "pachytene pirnas aravin", "pirnas aravin et", "aravin et al. 2008", "al. 2008 gan", "2008 gan et", "gan et al. 2011", "et al. 2011 .", "al. 2011 . pre", "2011 . pre pachytene", ". pre pachytene pirnas", "pre pachytene pirnas are", "pachytene pirnas are present", "pirnas are present prenatally", "are present prenatally in", "present prenatally in prospermatogonial", "prenatally in prospermatogonial cells", "in prospermatogonial cells and", "prospermatogonial cells and postnatally", "cells and postnatally in", "and postnatally in spermatogonial", "postnatally in spermatogonial cells.", "in spermatogonial cells. pachytene", "spermatogonial cells. pachytene pirnas", "cells. pachytene pirnas are", "pirnas are present in", "are present in more", "present in more mature", "in more mature postnatal", "more mature postnatal spermatocytes", "mature postnatal spermatocytes and", "postnatal spermatocytes and spermatids.", "spermatocytes and spermatids. the", "and spermatids. the pirnas", "spermatids. the pirnas derived", "the pirnas derived from", "pirnas derived from retroelements", "derived from retroelements comprise", "from retroelements comprise about", "retroelements comprise about half", "about half aravin", "half aravin et", "al. 2008 or", "2008 or less", "or less gan", "less gan et", "al. 2011 of", "2011 of the", "of the total pre", "the total pre pachytene", "total pre pachytene pirnas", "pachytene pirnas and the", "pirnas and the portion", "and the portion falls", "the portion falls sharply", "portion falls sharply from", "falls sharply from pre", "sharply from pre pachytene", "from pre pachytene to", "pre pachytene to pachytene", "to pachytene gan", "pachytene gan et", "et al. 2011 .
              in", "al. 2011 .
              in mice", ".
              in mice piwil2", "mili piwil2 gene", "piwil2 gene is", "gene is first", "is first detected in", "first detected in primordial", "detected in primordial germ", "in primordial germ cells", "primordial germ cells that", "germ cells that have", "cells that have reached", "that have reached the", "have reached the genital", "reached the genital ridge", "the genital ridge and", "genital ridge and expression", "ridge and expression persists", "and expression persists through", "expression persists through meiosis", "persists through meiosis in", "through meiosis in adults.", "meiosis in adults. piwil4", "adults. piwil4 miwi2", "miwi2 piwil4 gene", "piwil4 gene is", "gene is present", "is present in mouse", "present in mouse germ", "in mouse germ cells", "mouse germ cells during", "germ cells during de", "cells during de novo", "during de novo dna", "de novo dna methylation", "novo dna methylation shortly", "dna methylation shortly before", "methylation shortly before and", "shortly before and after", "before and after birth.", "and after birth. piwil1", "birth. piwil1 miwi", "miwi piwil1 gene", "piwil1 gene is", "is present during later", "present during later stages", "during later stages of", "later stages of meiosis", "stages of meiosis after", "of meiosis after birth", "after birth aravin", "birth aravin et", "et al. 2008 .", "al. 2008 . piwil4", "2008 . piwil4 and", ". piwil4 and piwil2", "piwil4 and piwil2 participate", "and piwil2 participate in", "piwil2 participate in re", "participate in re methylation", "in re methylation of", "re methylation of the", "methylation of the genome", "of the genome in", "the genome in mouse", "genome in mouse germ", "mouse germ cells and", "germ cells and consequent", "cells and consequent repression", "and consequent repression of", "consequent repression of transposable", "repression of transposable elements", "transposable elements carmell", "elements carmell et", "carmell et al. 2007", "al. 2007 aravin", "2007 aravin et", "al. 2008 kuramochi", "2008 kuramochi miyagawa", "kuramochi miyagawa et al.", "miyagawa et al. 2008", "al. 2008 zoch", "2008 zoch et", "zoch et al. 2020", "et al. 2020 .", "al. 2020 . in", "2020 . in mice", "in mice the", "mice the pirnas", "the pirnas bound by", "pirnas bound by piwil4", "bound by piwil4 bind", "by piwil4 bind nascent", "piwil4 bind nascent transcripts", "bind nascent transcripts of", "nascent transcripts of transposable", "transcripts of transposable elements", "of transposable elements and", "transposable elements and connects", "elements and connects to", "and connects to the", "connects to the de", "to the de novo", "the de novo dna", "novo dna methylation machinery", "dna methylation machinery via", "methylation machinery via spocd1", "machinery via spocd1 and", "via spocd1 and c19orf84", "spocd1 and c19orf84 to", "and c19orf84 to direct", "c19orf84 to direct dna", "to direct dna methylation", "direct dna methylation to", "dna methylation to the", "methylation to the transposable", "to the transposable elements", "transposable elements zoch", "elements zoch et", "al. 2020 2024", "2020 2024 .", "2024 . mutations in", ". mutations in spocd1", "mutations in spocd1 are", "in spocd1 are associated", "spocd1 are associated with", "are associated with infertility", "associated with infertility in", "with infertility in men", "in men zoch", "men zoch et", "zoch et al. 2024", "rnas pirnas are", "pirnas are short rnas", "are short rnas of 24", "short rnas of 24 31", "rnas of 24 31 nucleotides", "of 24 31 nucleotides that", "24 31 nucleotides that are", "31 nucleotides that are produced", "nucleotides that are produced by", "that are produced by cleavage", "are produced by cleavage of", "produced by cleavage of longer", "by cleavage of longer rnas", "cleavage of longer rnas and", "of longer rnas and amplification", "longer rnas and amplification by", "rnas and amplification by a", "and amplification by a \\ping", "amplification by a \\ping pong\\", "by a \\ping pong\\ mechanism", "a \\ping pong\\ mechanism involving", "\\ping pong\\ mechanism involving rounds", "pong\\ mechanism involving rounds of", "mechanism involving rounds of strand", "involving rounds of strand hybridization", "rounds of strand hybridization and", "of strand hybridization and cleavage", "hybridization and cleavage reviewed", "and cleavage reviewed in", "cleavage reviewed in sun", "reviewed in sun et al.", "in sun et al. 2022", "sun et al. 2022 .", "et al. 2022 . the", "al. 2022 . the pirnas", "2022 . the pirnas are", ". the pirnas are loaded", "the pirnas are loaded onto", "pirnas are loaded onto piwi", "are loaded onto piwi proteins", "onto piwi proteins piwil1", "proteins piwil1 piwil2", "piwil1 piwil2 piwil4", "piwil2 piwil4 that", "piwil4 that are then", "that are then guided by", "are then guided by base", "then guided by base pairing", "guided by base pairing of", "by base pairing of the", "base pairing of the pirnas", "pairing of the pirnas to", "of the pirnas to nascent", "the pirnas to nascent and", "pirnas to nascent and mature", "to nascent and mature transcripts", "and mature transcripts where", "mature transcripts where the", "transcripts where the piwi:pirna", "where the piwi:pirna complexes initiate", "the piwi:pirna complexes initiate transcriptional", "piwi:pirna complexes initiate transcriptional and", "complexes initiate transcriptional and post", "initiate transcriptional and post transcriptional", "transcriptional and post transcriptional silencing", "post transcriptional silencing respectively", "silencing respectively reviewed", "respectively reviewed in czech", "reviewed in czech et al.", "in czech et al. 2018", "et al. 2018 onishi", "al. 2018 onishi et", "2018 onishi et al.", "et al. 2021 wang", "al. 2021 wang et", "2021 wang et al.", "wang et al. 2023 .
              in", "et al. 2023 .
              in mice", "2023 .
              in mice sources", ".
              in mice sources of", "mice sources of pirnas", "sources of pirnas include transposon", "of pirnas include transposon rnas", "include transposon rnas long", "transposon rnas long non", "rnas long non coding", "non coding rnas exon", "coding rnas exon transcripts", "exon transcripts and rnas", "transcripts and rnas from", "and rnas from unannotated regions", "rnas from unannotated regions of", "from unannotated regions of the", "unannotated regions of the genome", "of the genome aravin", "the genome aravin et", "genome aravin et al.", "et al. 2007 2008", "al. 2007 2008 .", "2007 2008 . two", "2008 . two populations of", ". two populations of pirnas", "two populations of pirnas are", "populations of pirnas are observed", "of pirnas are observed during", "pirnas are observed during mouse", "are observed during mouse development:", "observed during mouse development: pre", "during mouse development: pre pachytene", "mouse development: pre pachytene pirnas", "development: pre pachytene pirnas and", "pre pachytene pirnas and pachytene", "pachytene pirnas and pachytene pirnas", "and pachytene pirnas aravin", "pachytene pirnas aravin et", "pirnas aravin et al.", "et al. 2008 gan", "al. 2008 gan et", "2008 gan et al.", "gan et al. 2011 .", "et al. 2011 . pre", "al. 2011 . pre pachytene", "2011 . pre pachytene pirnas", ". pre pachytene pirnas are", "pre pachytene pirnas are present", "pachytene pirnas are present prenatally", "pirnas are present prenatally in", "are present prenatally in prospermatogonial", "present prenatally in prospermatogonial cells", "prenatally in prospermatogonial cells and", "in prospermatogonial cells and postnatally", "prospermatogonial cells and postnatally in", "cells and postnatally in spermatogonial", "and postnatally in spermatogonial cells.", "postnatally in spermatogonial cells. pachytene", "in spermatogonial cells. pachytene pirnas", "spermatogonial cells. pachytene pirnas are", "cells. pachytene pirnas are present", "pachytene pirnas are present in", "pirnas are present in more", "are present in more mature", "present in more mature postnatal", "in more mature postnatal spermatocytes", "more mature postnatal spermatocytes and", "mature postnatal spermatocytes and spermatids.", "postnatal spermatocytes and spermatids. the", "spermatocytes and spermatids. the pirnas", "and spermatids. the pirnas derived", "spermatids. the pirnas derived from", "the pirnas derived from retroelements", "pirnas derived from retroelements comprise", "derived from retroelements comprise about", "from retroelements comprise about half", "comprise about half aravin", "about half aravin et", "half aravin et al.", "et al. 2008 or", "al. 2008 or less", "or less gan et", "less gan et al.", "et al. 2011 of", "al. 2011 of the", "2011 of the total", "of the total pre pachytene", "the total pre pachytene pirnas", "total pre pachytene pirnas and", "pre pachytene pirnas and the", "pachytene pirnas and the portion", "pirnas and the portion falls", "and the portion falls sharply", "the portion falls sharply from", "portion falls sharply from pre", "falls sharply from pre pachytene", "sharply from pre pachytene to", "from pre pachytene to pachytene", "pachytene to pachytene gan", "to pachytene gan et", "pachytene gan et al.", "gan et al. 2011 .
              in", "et al. 2011 .
              in mice", "2011 .
              in mice piwil2", "mice piwil2 mili", "piwil2 mili piwil2", "piwil2 gene is first", "gene is first detected", "is first detected in primordial", "first detected in primordial germ", "detected in primordial germ cells", "in primordial germ cells that", "primordial germ cells that have", "germ cells that have reached", "cells that have reached the", "that have reached the genital", "have reached the genital ridge", "reached the genital ridge and", "the genital ridge and expression", "genital ridge and expression persists", "ridge and expression persists through", "and expression persists through meiosis", "expression persists through meiosis in", "persists through meiosis in adults.", "through meiosis in adults. piwil4", "in adults. piwil4 miwi2", "piwil4 miwi2 piwil4", "piwil4 gene is present", "gene is present in", "is present in mouse germ", "present in mouse germ cells", "in mouse germ cells during", "mouse germ cells during de", "germ cells during de novo", "cells during de novo dna", "during de novo dna methylation", "de novo dna methylation shortly", "novo dna methylation shortly before", "dna methylation shortly before and", "methylation shortly before and after", "shortly before and after birth.", "before and after birth. piwil1", "after birth. piwil1 miwi", "piwil1 miwi piwil1", "piwil1 gene is present", "gene is present during", "is present during later stages", "present during later stages of", "during later stages of meiosis", "later stages of meiosis after", "stages of meiosis after birth", "meiosis after birth aravin", "after birth aravin et", "birth aravin et al.", "aravin et al. 2008 .", "et al. 2008 . piwil4", "al. 2008 . piwil4 and", "2008 . piwil4 and piwil2", ". piwil4 and piwil2 participate", "piwil4 and piwil2 participate in", "and piwil2 participate in re", "piwil2 participate in re methylation", "participate in re methylation of", "in re methylation of the", "re methylation of the genome", "methylation of the genome in", "of the genome in mouse", "the genome in mouse germ", "genome in mouse germ cells", "in mouse germ cells and", "mouse germ cells and consequent", "germ cells and consequent repression", "cells and consequent repression of", "and consequent repression of transposable", "consequent repression of transposable elements", "of transposable elements carmell", "transposable elements carmell et", "elements carmell et al.", "et al. 2007 aravin", "al. 2007 aravin et", "2007 aravin et al.", "et al. 2008 kuramochi", "al. 2008 kuramochi miyagawa", "2008 kuramochi miyagawa et", "kuramochi miyagawa et al. 2008", "et al. 2008 zoch", "al. 2008 zoch et", "2008 zoch et al.", "zoch et al. 2020 .", "et al. 2020 . in", "al. 2020 . in mice", ". in mice the", "in mice the pirnas", "mice the pirnas bound", "the pirnas bound by piwil4", "pirnas bound by piwil4 bind", "bound by piwil4 bind nascent", "by piwil4 bind nascent transcripts", "piwil4 bind nascent transcripts of", "bind nascent transcripts of transposable", "nascent transcripts of transposable elements", "transcripts of transposable elements and", "of transposable elements and connects", "transposable elements and connects to", "elements and connects to the", "and connects to the de", "connects to the de novo", "to the de novo dna", "the de novo dna methylation", "de novo dna methylation machinery", "novo dna methylation machinery via", "dna methylation machinery via spocd1", "methylation machinery via spocd1 and", "machinery via spocd1 and c19orf84", "via spocd1 and c19orf84 to", "spocd1 and c19orf84 to direct", "and c19orf84 to direct dna", "c19orf84 to direct dna methylation", "to direct dna methylation to", "direct dna methylation to the", "dna methylation to the transposable", "methylation to the transposable elements", "the transposable elements zoch", "transposable elements zoch et", "elements zoch et al.", "et al. 2020 2024", "al. 2020 2024 .", "2020 2024 . mutations", "2024 . mutations in spocd1", ". mutations in spocd1 are", "mutations in spocd1 are associated", "in spocd1 are associated with", "spocd1 are associated with infertility", "are associated with infertility in", "associated with infertility in men", "infertility in men zoch", "in men zoch et", "men zoch et al." ] }, { "record_id": "GLY_000594_1_2158", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9860276", "r hsa", "hsa 9860276", "r hsa 9860276" ] }, { "record_id": "GLY_000594_1_2158", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "slc15a4:tasl dependent", "dependent irf5", "irf5 activation", "slc15a4:tasl dependent irf5", "dependent irf5 activation", "slc15a4:tasl dependent irf5 activation", "this reactome", "reactome module", "module describes", "describes the", "the toll", "toll like", "like receptor", "receptor 7", "or tlr9", "tlr9 \u2013", "\u2013 induced", "induced activation", "activation of", "of interferon", "interferon regulatory", "regulatory factor", "factor 5", "via the", "the slc15a4:tasl", "slc15a4:tasl axis.", "axis.

              solute", "

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              ", "this reactome module", "reactome module describes", "module describes the", "describes the toll", "the toll like", "toll like receptor", "like receptor 7", "7 tlr7", "tlr8 or", "or tlr9 \u2013", "tlr9 \u2013 induced", "\u2013 induced activation", "induced activation of", "activation of interferon", "of interferon regulatory", "interferon regulatory factor", "regulatory factor 5", "5 irf5", "irf5 via", "via the slc15a4:tasl", "the slc15a4:tasl axis.", "slc15a4:tasl axis.

              solute", "axis.

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              solute", "slc15a4:tasl axis.

              solute carrier", "axis.

              solute carrier family", "

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              ", "this reactome module describes the", "reactome module describes the toll", "module describes the toll like", "describes the toll like receptor", "the toll like receptor 7", "like receptor 7 tlr7", "tlr8 or tlr9 \u2013", "or tlr9 \u2013 induced activation", "tlr9 \u2013 induced activation of", "\u2013 induced activation of interferon", "induced activation of interferon regulatory", "activation of interferon regulatory factor", "of interferon regulatory factor 5", "regulatory factor 5 irf5", "5 irf5 via", "irf5 via the slc15a4:tasl", "via the slc15a4:tasl axis.

              solute", "the slc15a4:tasl axis.

              solute carrier", "slc15a4:tasl axis.

              solute carrier family", "axis.

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"endosomes/lysosomes heinz lx. et", "lx. et al. 2020", "al. 2020 kobayashi", "2020 kobayashi t et", "t et al. 2021", "et al. 2021 .", "al. 2021 . slc15a4", "2021 . slc15a4 acts as", ". slc15a4 acts as a", "slc15a4 acts as a signaling", "acts as a signaling scaffold", "a signaling scaffold recruiting", "signaling scaffold recruiting the", "scaffold recruiting the protein", "recruiting the protein tlr adaptor", "the protein tlr adaptor interacting", "protein tlr adaptor interacting with", "tlr adaptor interacting with slc15a4", "adaptor interacting with slc15a4 on", "interacting with slc15a4 on the", "with slc15a4 on the lysosome", "on the lysosome tasl", "lysosome tasl to", "tasl to the cytosolic", "to the cytosolic surface of", "the cytosolic surface of endolysosomes", "surface of endolysosomes heinz", "of endolysosomes heinz lx.", "endolysosomes heinz lx. et", "al. 2020 custodio", "2020 custodio tf et", "tf et al. 2023", "al. 2023 chen", "2023 chen x et", "x et al. 2023", "et al. 2023 .", "al. 2023 . upon", "2023 . upon activation of", ". upon activation of endosomal", "upon activation of endosomal tlr", "activation of endosomal tlr signaling", "endosomal tlr signaling tasl", "tlr signaling tasl undergoes", "signaling tasl undergoes phosphorylation", "tasl undergoes phosphorylation and recruits", "undergoes phosphorylation and recruits irf5", "phosphorylation and recruits irf5 to", "and recruits irf5 to its", "recruits irf5 to its plxis", "irf5 to its plxis motif", "its plxis motif heinz", "plxis motif heinz lx.", "motif heinz lx. et", "et al. 2020 .", "al. 2020 . the", "2020 . the slc15a4:tasl complex", ". the slc15a4:tasl complex facilitates", "the slc15a4:tasl complex facilitates irf5", "slc15a4:tasl complex facilitates irf5 phosphorylation", "complex facilitates irf5 phosphorylation by", "facilitates irf5 phosphorylation by ikbkb", "phosphorylation by ikbkb ikk\u03b2", "ikbkb ikk\u03b2 and", "ikk\u03b2 and subsequent irf5", "and subsequent irf5 homodimerization downstream", "subsequent irf5 homodimerization downstream of", "irf5 homodimerization downstream of tlr7", "homodimerization downstream of tlr7 tlr9", "of tlr7 tlr9 heinz", "tlr7 tlr9 heinz lx.", "tlr9 heinz lx. et", "al. 2020 zhang", "2020 zhang h et", "h et al. 2023", "al. 2023 boeszoermeny", "2023 boeszoermeny a et", "a et al. 2023", "al. 2023 . once", ". once activated irf5", "once activated irf5 translocates", "activated irf5 translocates to", "irf5 translocates to the nucleus", "translocates to the nucleus to", "to the nucleus to induce", "the nucleus to induce the", "nucleus to induce the transcription", "to induce the transcription of", "induce the transcription of genes", "the transcription of genes encoding", "transcription of genes encoding type", "of genes encoding type i", "genes encoding type i interferons", "type i interferons ifns", "interferons ifns and", "ifns and pro inflammatory", "and pro inflammatory cytokines. hyperactivation", "pro inflammatory cytokines. hyperactivation of", "inflammatory cytokines. hyperactivation of the", "cytokines. hyperactivation of the slc15a4:tasl:irf5", "hyperactivation of the slc15a4:tasl:irf5 pathway", "the slc15a4:tasl:irf5 pathway often", "slc15a4:tasl:irf5 pathway often caused", "pathway often caused by", "often caused by the detection", "caused by the detection of", "by the detection of endogenous", "the detection of endogenous nucleic", "detection of endogenous nucleic acids", "endogenous nucleic acids leads", "nucleic acids leads to", "acids leads to increased", "leads to increased production of", "to increased production of type", "increased production of type i", "production of type i ifns", "of type i ifns and", "type i ifns and is", "i ifns and is associated", "ifns and is associated with", "and is associated with pathogenesis", "is associated with pathogenesis of", "associated with pathogenesis of inflammatory", "with pathogenesis of inflammatory diseases", "pathogenesis of inflammatory diseases such", "of inflammatory diseases such as", "inflammatory diseases such as systemic", "diseases such as systemic lupus", "such as systemic lupus erythematosus", "systemic lupus erythematosus sle", "sle odhams ca", "ca et al. 2019", "al. 2019 heinz", "2019 heinz lx. et", "et al. 2021 .
              " ] }, { "record_id": "GLY_000594_1_2159", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9865881", "r hsa", "hsa 9865881", "r hsa 9865881" ] }, { "record_id": "GLY_000594_1_2159", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "complex iii", "iii assembly", "complex iii assembly", "assembly of", "of the", "the cytochrome", "cytochrome c", "cytochrome bc1", "was mainly", "mainly investigated", "investigated in", "in yeast.", "yeast. the", "the process", "process in", "in humans", "humans is", "is considered", "considered to", "to recapitulate", "recapitulate the", "in the", "the yeast", "yeast system", "system based", "based on", "on the", "the high", "high similarity", "similarity in", "in structure", "structure and", "and composition", "composition of", "yeast and", "and human", "human complexes.", "complexes. human", "human complex", "iii probably", "probably consists", 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"up by", "by respiratory", "respiratory electron", "electron transport", "transport does", "does not", "not go", "go entirely", "entirely into", "into atp", "atp production.", "production. transport", "transport proteins", "proteins of", "of the", "the slc25", "slc25 type", "type utilize", "utilize the", "the gradient", "gradient to", "to symport", "symport small", "small molecules", "molecules with", "with protons", "protons into", "into the", "the matrix", "simultaneously generating", "generating heat", "\\thermogenesis\\ .", ". ucp1", "ucp1 and", "and aac1", "aac1 have", "have been", "been shown", "shown to", "to import", "import protons", "protons exclusively", "exclusively and", "and are", "are responsible", "responsible for", "for most", "most heat", "heat generated", "generated in", "in brown", "brown fat", "fat and", "and other", "other tissue", "reviewed in", "in bertholet", "bertholet &", "& kirichok", "2022 .

              uncoupling", ".

              uncoupling proteins", "are members", "members of", "the mitochondrial", "mitochondrial transport", "transport carrier", "carrier family.", "family. the", "the crystal", "crystal structure", "structure of", "of one", "one member", "member of", "the family", "the adenine", "adenine nucleotide", "nucleotide translocase", "is known", "and ucps", "ucps can", "can be", "be successfully", "successfully folded", "folded into", "into this", "this structure", "structure to", "to indicate", "indicate their", "their probable", "probable 3d", "3d arrangement", "pebay peyroula", "peyroula et", "et al.", "al. 2003", "kunji 2004", "esteves &", "& brand", "brand 2005", "2005 .

              the", ".

              the most", "most studied", "studied member", "catalyzes adaptive", "adaptive thermogenesis", "heat generation", "in mammalian", "mammalian brown", "brown adipose", "adipose tissue.", "tissue. it", "it does", "does so", "so by", "by promoting", "promoting a", "a leak", "leak of", "of protons", "protons through", "through the", "mitochondrial inner", "inner membrane", "which uncouples", "uncouples atp", "atp production", "production from", "from substrate", "substrate oxidation", "leading to", "to fast", "fast oxygen", "oxygen consumption", "consumption and", "and ultimately", "ultimately to", "to heat", "heat production.", "production. the", "the thermogenic", "thermogenic activity", "activity of", "of ucp1", "ucp1 in", "adipose tissue", "tissue plays", "plays an", "an important", "important role", "role when", "when the", "the organism", "organism needs", "needs extra", "extra heat", "during cold", "cold weather", "weather conditions", "for small", "small rodents", "the cold", "cold stress", "stress of", "of birth", "or arousal", "arousal from", "from hibernation.", "hibernation. ucp1", "ucp1 homologs", "homologs have", "been found", "found in", "in lower", "lower vertebrates", "vertebrates such", "such as", "as fish", "where their", "their role", "role is", "is unclear", "cannon &", "& nedergaard", "nedergaard 2004", "jastroch et", "al. 2005", ".

              the proton", "proton conductance", "conductance of", "tissue is", "is tightly", "tightly controlled.", "controlled. it", "it is", "is strongly", "strongly inhibited", "inhibited by", "by physiological", "physiological concentrations", "concentrations of", "of purine", "purine nucleotides.", "nucleotides. this", "this inhibition", "inhibition is", "is overcome", "overcome by", "by fatty", "fatty acids", "acids released", "released from", "from intracellular", "intracellular triacylglycerol", "triacylglycerol stores", "stores following", "following adrenergic", "adrenergic activation", "activation in", "in response", "response to", "to cold", "cold or", "or overfeeding.", "overfeeding. other", "other activators", "activators include", "include superoxide", "retinoic acid", "the retinoid", "retinoid 4", "5 6", "6 7", "7 8", "8 tetrahydro", "tetrahydro 5", "5 5", "5 8", "8 8", "8 tetra", "tetra methyl", "methyl 2", "2 naphtalenyl", "1 propenyl", "propenyl benzoic", "benzoic acid", "and reactive", "reactive alkenals", "as hydroxynonenal.", "hydroxynonenal.

              there", "

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              ", "

              several", "several models", "models have", "been proposed", "proposed for", "for the", "the molecular", "molecular mechanism", "mechanism by", "by which", "which fatty", "acids lead", "lead to", "to increased", "increased proton", "conductance by", "by ucp1", "tissue mitochondria", "mitochondria and", "and presumably", "presumably by", "by the", "the other", "other ucps.", "ucps. we", "we have", "have depicted", "depicted the", "the most", "most likely", "likely model", "the \\fatty", "\\fatty acid", "acid cycling\\", "cycling\\ model", "in this", "this pathway", "pathway .

              studies", ".

              studies of", "of mouse", "mouse models", "models and", "and cultured", "cultured human", "human cells", "cells have", "have suggested", "suggested that", "that oleoyl", "oleoyl phenylalanine", "synthesized by", "by extracellular", "extracellular pm20d1", "may play", "play a", "a role", "role in", "in uncoupling", "uncoupling independent", "independent of", "the action", "action of", "of ucps", "long et", "2016 .", ". its", "its synthesis", "synthesis and", "and hydrolysis", "hydrolysis are", "are annotated", "annotated here.", "the protonmotive force", "protonmotive force across", "force across the", "across the inner", "the inner mitochondrial", "inner mitochondrial membrane", "mitochondrial membrane built", "membrane built up", "built up by", "up by respiratory", "by respiratory electron", "respiratory electron transport", "electron transport does", "transport does not", "does not go", "not go entirely", "go entirely into", "entirely into atp", "into atp production.", "atp production. transport", "production. transport proteins", "transport proteins of", "proteins of the", "of the slc25", "the slc25 type", "slc25 type utilize", "type utilize the", "utilize the gradient", "the gradient to", "gradient to symport", "to symport small", "symport small molecules", "small molecules with", "molecules with protons", "with protons into", "protons into the", "into the matrix", "matrix simultaneously", "simultaneously generating heat", "heat \\thermogenesis\\", "\\thermogenesis\\ . ucp1", ". ucp1 and", "ucp1 and aac1", "and aac1 have", "aac1 have been", "have been shown", "been shown to", "shown to import", "to import protons", "import protons exclusively", "protons exclusively and", "exclusively and are", "and are responsible", "are responsible for", "responsible for most", "for most heat", "most heat generated", "heat generated in", "generated in brown", "in brown fat", "brown fat and", "fat and other", "and other tissue", "tissue respectively", "respectively reviewed", "reviewed in bertholet", "in bertholet &", "bertholet & kirichok", "kirichok 2022", "2022 .

              uncoupling proteins", "proteins ucps", "ucps are", "are members of", "members of the", "of the mitochondrial", "the mitochondrial transport", "mitochondrial transport carrier", "transport carrier family.", "carrier family. the", "family. the crystal", "the crystal structure", "crystal structure of", "structure of one", "of one member", "one member of", "member of the", "of the family", "family the", "the adenine nucleotide", "adenine nucleotide translocase", "translocase is", "known and", "and ucps can", "ucps can be", "can be successfully", "be successfully folded", "successfully folded into", "folded into this", "into this structure", "this structure to", "structure to indicate", "to indicate their", "indicate their probable", "their probable 3d", "probable 3d arrangement", "arrangement pebay", "pebay peyroula et", "peyroula et al.", "et al. 2003", "2003 kunji", "2004 esteves", "esteves & brand", "& brand 2005", "brand 2005 .

              the", "2005 .

              the most", ".

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              the", "2005 .

              the proton", ".

              the proton conductance", "proton conductance of", "conductance of ucp1", "adipose tissue is", "tissue is tightly", "is tightly controlled.", "tightly controlled. it", "controlled. it is", "it is strongly", "is strongly inhibited", "strongly inhibited by", "inhibited by physiological", "by physiological concentrations", "physiological concentrations of", "concentrations of purine", "of purine nucleotides.", "purine nucleotides. this", "nucleotides. this inhibition", "this inhibition is", "inhibition is overcome", "is overcome by", "overcome by fatty", "by fatty acids", "fatty acids released", "acids released from", "released from intracellular", "from intracellular triacylglycerol", "intracellular triacylglycerol stores", "triacylglycerol stores following", "stores following adrenergic", "following adrenergic activation", "adrenergic activation in", "activation in response", "in response to", "response to cold", "to cold or", "cold or overfeeding.", "or overfeeding. other", "overfeeding. other activators", "other activators include", "activators include superoxide", "superoxide retinoic", "acid the", "the retinoid 4", "e 2", "2 5", "5 6 7", "6 7 8", "7 8 tetrahydro", "8 tetrahydro 5", "tetrahydro 5 5", "5 5 8", "5 8 8", "8 8 tetra", "8 tetra methyl", "tetra methyl 2", "methyl 2 naphtalenyl", "naphtalenyl 1", "1 propenyl benzoic", "propenyl benzoic acid", "acid ttnpb", "ttnpb and", "and reactive alkenals", "alkenals such", "such as hydroxynonenal.", "as hydroxynonenal.

              there", "hydroxynonenal.

              there is", "

              there is strong", "is strong evidence", "strong evidence that", "evidence that the", "that the regulated", "the regulated uncoupling", "regulated uncoupling caused", "uncoupling caused by", "caused by these", "by these proteins", "these proteins attenuates", "proteins attenuates mitochondrial", "attenuates mitochondrial reactive", "mitochondrial reactive oxygen", "reactive oxygen species", "oxygen species production", "production protects", "protects against cellular", "against cellular damage", "damage and", "and in", "in beta cells", "cells diminishes", "diminishes insulin secretion.", "insulin secretion. there", "secretion. there are", "there are also", "are also untested", "also untested suggestions", "untested suggestions that", "suggestions that their", "that their transport", "their transport of", "transport of fatty", "of fatty acids", "fatty acids may", "acids may be", "may be physiologically", "be physiologically important", "important brand", "brand & esteves", "& esteves 2005", "2005 krauss", "krauss et al.", "al. 2005 .", "2005 .

              ", ".

              several", "

              several models", "several models have", "models have been", "have been proposed", "been proposed for", "proposed for the", "for the molecular", "the molecular mechanism", "molecular mechanism by", "mechanism by which", "by which fatty", "which fatty acids", "fatty acids lead", "acids lead to", "lead to increased", "to increased proton", "increased proton conductance", "proton conductance by", "conductance by ucp1", "by ucp1 in", "adipose tissue mitochondria", "tissue mitochondria and", "mitochondria and presumably", "and presumably by", "presumably by the", "by the other", "the other ucps.", "other ucps. we", "ucps. we have", "we have depicted", "have depicted the", "depicted the most", "the most likely", "most likely model", "model the", "the \\fatty acid", "\\fatty acid cycling\\", "acid cycling\\ model", "model in", "in this pathway", "this pathway .

              studies", "pathway .

              studies of", ".

              studies of mouse", "of mouse models", "mouse models and", "models and cultured", "and cultured human", "cultured human cells", "human cells have", "cells have suggested", "have suggested that", "suggested that oleoyl", "that oleoyl phenylalanine", "phenylalanine synthesized", "synthesized by extracellular", "by extracellular pm20d1", "pm20d1 may", "may play a", "play a role", "a role in", "role in uncoupling", "in uncoupling independent", "uncoupling independent of", "independent of the", "of the action", "the action of", "action of ucps", "ucps long", "long et al.", "al. 2016", "2016 . its", ". its synthesis", "its synthesis and", "synthesis and hydrolysis", "and hydrolysis are", "hydrolysis are annotated", "are annotated here.", "the protonmotive force across", "protonmotive force across the", "force across the inner", "across the inner mitochondrial", "the inner mitochondrial membrane", "inner mitochondrial membrane built", "mitochondrial membrane built up", "membrane built up by", "built up by respiratory", "up by respiratory electron", "by respiratory electron transport", "respiratory electron transport does", "electron transport does not", "transport does not go", "does not go entirely", "not go entirely into", "go entirely into atp", "entirely into atp production.", "into atp production. transport", "atp production. transport proteins", "production. transport proteins of", "transport proteins of the", "proteins of the slc25", "of the slc25 type", "the slc25 type utilize", "slc25 type utilize the", "type utilize the gradient", "utilize the gradient to", "the gradient to symport", "gradient to symport small", "to symport small molecules", "symport small molecules with", "small molecules with protons", "molecules with protons into", "with protons into the", "protons into the matrix", "the matrix simultaneously", "matrix simultaneously generating", "generating heat \\thermogenesis\\", "heat \\thermogenesis\\ .", "\\thermogenesis\\ . ucp1 and", ". ucp1 and aac1", "ucp1 and aac1 have", "and aac1 have been", "aac1 have been shown", "have been shown to", "been shown to import", "shown to import protons", "to import protons exclusively", "import protons exclusively and", "protons exclusively and are", "exclusively and are responsible", "and are responsible for", "are responsible for most", "responsible for most heat", "for most heat generated", "most heat generated in", "heat generated in brown", "generated in brown fat", "in brown fat and", "brown fat and other", "fat and other tissue", "other tissue respectively", "respectively reviewed in", "reviewed in bertholet &", "in bertholet & kirichok", "& kirichok 2022", "kirichok 2022 .

              uncoupling", ".

              uncoupling proteins ucps", "ucps are members", "are members of the", "members of the mitochondrial", "of the mitochondrial transport", "the mitochondrial transport carrier", "mitochondrial transport carrier family.", "transport carrier family. the", "carrier family. the crystal", "family. the crystal structure", "the crystal structure of", "crystal structure of one", "structure of one member", "of one member of", "one member of the", "member of the family", "the family the", "family the adenine", "the adenine nucleotide translocase", "nucleotide translocase is", "translocase is known", "is known and", "known and ucps", "and ucps can be", "ucps can be successfully", "can be successfully folded", "be successfully folded into", "successfully folded into this", "folded into this structure", "into this structure to", "this structure to indicate", "structure to indicate their", "to indicate their probable", "indicate their probable 3d", "their probable 3d arrangement", "3d arrangement pebay", "arrangement pebay peyroula", "pebay peyroula et al.", "peyroula et al. 2003", "al. 2003 kunji", "2003 kunji 2004", "kunji 2004 esteves", "2004 esteves &", "esteves & brand 2005", "& brand 2005 .

              the", "brand 2005 .

              the most", "2005 .

              the most studied", ".

              the most studied member", "most studied member of", "studied member of the", "the family ucp1", "ucp1 catalyzes adaptive", "adaptive thermogenesis i.e.", "i.e. heat generation", "heat generation in", "generation in mammalian", "in mammalian brown adipose", "mammalian brown adipose tissue.", "brown adipose tissue. it", "adipose tissue. it does", "tissue. it does so", "it does so by", "does so by promoting", "so by promoting a", "by promoting a leak", "promoting a leak of", "a leak of protons", "leak of protons through", "of protons through the", "protons through the mitochondrial", "through the mitochondrial inner", "the mitochondrial inner membrane", "inner membrane which", "membrane which uncouples", "which uncouples atp production", "uncouples atp production from", "atp production from substrate", "production from substrate oxidation", "substrate oxidation leading", "oxidation leading to", "leading to fast oxygen", "to fast oxygen consumption", "fast oxygen consumption and", "oxygen consumption and ultimately", "consumption and ultimately to", "and ultimately to heat", "ultimately to heat production.", "to heat production. the", "heat production. the thermogenic", "production. the thermogenic activity", "the thermogenic activity of", "thermogenic activity of ucp1", "activity of ucp1 in", "of ucp1 in brown", "ucp1 in brown adipose", "in brown adipose tissue", "brown adipose tissue plays", "adipose tissue plays an", "tissue plays an important", "plays an important role", "an important role when", "important role when the", "role when the organism", "when the organism needs", "the organism needs extra", "organism needs extra heat", "extra heat e.g.", "e.g. during cold", "during cold weather conditions", "weather conditions for", "conditions for small", "rodents the", "the cold stress of", "cold stress of birth", "of birth or", "birth or arousal", "or arousal from hibernation.", "arousal from hibernation. ucp1", "from hibernation. ucp1 homologs", "hibernation. ucp1 homologs have", "ucp1 homologs have been", "homologs have been found", "have been found in", "been found in lower", "found in lower vertebrates", "in lower vertebrates such", "lower vertebrates such as", "vertebrates such as fish", "as fish where", "fish where their", "where their role is", "their role is unclear", "is unclear cannon", "unclear cannon &", "cannon & nedergaard 2004", "nedergaard 2004 jastroch", "2004 jastroch et", "jastroch et al. 2005", "et al. 2005 .

              the", "al. 2005 .

              the proton", "2005 .

              the proton conductance", ".

              the proton conductance of", "proton conductance of ucp1", "conductance of ucp1 in", "brown adipose tissue is", "adipose tissue is tightly", "tissue is tightly controlled.", "is tightly controlled. it", "tightly controlled. it is", "controlled. it is strongly", "it is strongly inhibited", "is strongly inhibited by", "strongly inhibited by physiological", "inhibited by physiological concentrations", "by physiological concentrations of", "physiological concentrations of purine", "concentrations of purine nucleotides.", "of purine nucleotides. this", "purine nucleotides. this inhibition", "nucleotides. this inhibition is", "this inhibition is overcome", "inhibition is overcome by", "is overcome by fatty", "overcome by fatty acids", "by fatty acids released", "fatty acids released from", "acids released from intracellular", "released from intracellular triacylglycerol", "from intracellular triacylglycerol stores", "intracellular triacylglycerol stores following", "triacylglycerol stores following adrenergic", "stores following adrenergic activation", "following adrenergic activation in", "adrenergic activation in response", "activation in response to", "in response to cold", "response to cold or", "to cold or overfeeding.", "cold or overfeeding. other", "or overfeeding. other activators", "overfeeding. other activators include", "other activators include superoxide", "include superoxide retinoic", "superoxide retinoic acid", "retinoic acid the", "acid the retinoid", "4 e", "2 5 6", "5 6 7 8", "6 7 8 tetrahydro", "7 8 tetrahydro 5", "8 tetrahydro 5 5", "tetrahydro 5 5 8", "5 5 8 8", "5 8 8 tetra", "8 8 tetra methyl", "8 tetra methyl 2", "tetra methyl 2 naphtalenyl", "2 naphtalenyl 1", "naphtalenyl 1 propenyl", "1 propenyl benzoic acid", "benzoic acid ttnpb", "ttnpb and reactive", "reactive alkenals such", "alkenals such as", "such as hydroxynonenal.

              there", "as hydroxynonenal.

              there is", "hydroxynonenal.

              there is strong", "

              there is strong evidence", "is strong evidence that", "strong evidence that the", "evidence that the regulated", "that the regulated uncoupling", "the regulated uncoupling caused", "regulated uncoupling caused by", "uncoupling caused by these", "caused by these proteins", "by these proteins attenuates", "these proteins attenuates mitochondrial", "proteins attenuates mitochondrial reactive", "attenuates mitochondrial reactive oxygen", "mitochondrial reactive oxygen species", "reactive oxygen species production", "species production protects", "production protects against", "protects against cellular damage", "cellular damage and", "and in beta", "beta cells diminishes", "cells diminishes insulin", "diminishes insulin secretion. there", "insulin secretion. there are", "secretion. there are also", "there are also untested", "are also untested suggestions", "also untested suggestions that", "untested suggestions that their", "suggestions that their transport", "that their transport of", "their transport of fatty", "transport of fatty acids", "of fatty acids may", "fatty acids may be", "acids may be physiologically", "may be physiologically important", "physiologically important brand", "important brand &", "brand & esteves 2005", "2005 esteves", "brand 2005 krauss", "2005 krauss et", "krauss et al. 2005", "et al. 2005 .", "al. 2005 .

              ", "2005 .

              several", ".

              several models", "

              several models have", "several models have been", "models have been proposed", "have been proposed for", "been proposed for the", "proposed for the molecular", "for the molecular mechanism", "the molecular mechanism by", "molecular mechanism by which", "mechanism by which fatty", "by which fatty acids", "which fatty acids lead", "fatty acids lead to", "acids lead to increased", "lead to increased proton", "to increased proton conductance", "increased proton conductance by", "proton conductance by ucp1", "conductance by ucp1 in", "by ucp1 in brown", "brown adipose tissue mitochondria", "adipose tissue mitochondria and", "tissue mitochondria and presumably", "mitochondria and presumably by", "and presumably by the", "presumably by the other", "by the other ucps.", "the other ucps. we", "other ucps. we have", "ucps. we have depicted", "we have depicted the", "have depicted the most", "depicted the most likely", "the most likely model", "likely model the", "model the \\fatty", "the \\fatty acid cycling\\", "\\fatty acid cycling\\ model", "cycling\\ model in", "model in this", "in this pathway .

              studies", "this pathway .

              studies of", "pathway .

              studies of mouse", ".

              studies of mouse models", "of mouse models and", "mouse models and cultured", "models and cultured human", "and cultured human cells", "cultured human cells have", "human cells have suggested", "cells have suggested that", "have suggested that oleoyl", "suggested that oleoyl phenylalanine", "oleoyl phenylalanine synthesized", "phenylalanine synthesized by", "synthesized by extracellular pm20d1", "extracellular pm20d1 may", "pm20d1 may play", "may play a role", "play a role in", "a role in uncoupling", "role in uncoupling independent", "in uncoupling independent of", "uncoupling independent of the", "independent of the action", "of the action of", "the action of ucps", "of ucps long", "ucps long et", "et al. 2016", "al. 2016 .", "2016 . its synthesis", ". its synthesis and", "its synthesis and hydrolysis", "synthesis and hydrolysis are", "and hydrolysis are annotated", "hydrolysis are annotated here.", "the protonmotive force across the", "protonmotive force across the inner", "force across the inner mitochondrial", "across the inner mitochondrial membrane", "the inner mitochondrial membrane built", "inner mitochondrial membrane built up", "mitochondrial membrane built up by", "membrane built up by respiratory", "built up by respiratory electron", "up by respiratory electron transport", "by respiratory electron transport does", "respiratory electron transport does not", "electron transport does not go", "transport does not go entirely", "does not go entirely into", "not go entirely into atp", "go entirely into atp production.", "entirely into atp production. transport", "into atp production. transport proteins", "atp production. transport proteins of", "production. transport proteins of the", "transport proteins of the slc25", "proteins of the slc25 type", "of the slc25 type utilize", "the slc25 type utilize the", "slc25 type utilize the gradient", "type utilize the gradient to", "utilize the gradient to symport", "the gradient to symport small", "gradient to symport small molecules", "to symport small molecules with", "symport small molecules with protons", "small molecules with protons into", "molecules with protons into the", "with protons into the matrix", "into the matrix simultaneously", "the matrix simultaneously generating", "matrix simultaneously generating heat", "simultaneously generating heat \\thermogenesis\\", "generating heat \\thermogenesis\\ .", "heat \\thermogenesis\\ . ucp1", "\\thermogenesis\\ . ucp1 and aac1", ". ucp1 and aac1 have", "ucp1 and aac1 have been", "and aac1 have been shown", "aac1 have been shown to", "have been shown to import", "been shown to import protons", "shown to import protons exclusively", "to import protons exclusively and", "import protons exclusively and are", "protons exclusively and are responsible", "exclusively and are responsible for", "and are responsible for most", "are responsible for most heat", "responsible for most heat generated", "for most heat generated in", "most heat generated in brown", "heat generated in brown fat", "generated in brown fat and", "in brown fat and other", "brown fat and other tissue", "and other tissue respectively", "tissue respectively reviewed", "respectively reviewed in bertholet", "reviewed in bertholet & kirichok", "bertholet & kirichok 2022", "& kirichok 2022 .

              uncoupling", "kirichok 2022 .

              uncoupling proteins", "2022 .

              uncoupling proteins ucps", "proteins ucps are", "ucps are members of", "are members of the mitochondrial", "members of the mitochondrial transport", "of the mitochondrial transport carrier", "the mitochondrial transport carrier family.", "mitochondrial transport carrier family. the", "transport carrier family. the crystal", "carrier family. the crystal structure", "family. the crystal structure of", "the crystal structure of one", "crystal structure of one member", "structure of one member of", "of one member of the", "one member of the family", "of the family the", "the family the adenine", "family the adenine nucleotide", "adenine nucleotide translocase is", "nucleotide translocase is known", "is known and ucps", "known and ucps can", "and ucps can be successfully", "ucps can be successfully folded", "can be successfully folded into", "be successfully folded into this", "successfully folded into this structure", "folded into this structure to", "into this structure to indicate", "this structure to indicate their", "structure to indicate their probable", "to indicate their probable 3d", "indicate their probable 3d arrangement", "probable 3d arrangement pebay", "3d arrangement pebay peyroula", "arrangement pebay peyroula et", "pebay peyroula et al. 2003", "et al. 2003 kunji", "al. 2003 kunji 2004", "kunji 2004 esteves &", "2004 esteves & brand", "esteves & brand 2005 .

              the", "& brand 2005 .

              the most", "brand 2005 .

              the most studied", "2005 .

              the most studied member", ".

              the most studied member of", "most studied member of the", "studied member of the family", "of the family ucp1", "family ucp1 catalyzes", "ucp1 catalyzes adaptive thermogenesis", "catalyzes adaptive thermogenesis i.e.", "thermogenesis i.e. heat", "heat generation in mammalian", "generation in mammalian brown", "in mammalian brown adipose tissue.", "mammalian brown adipose tissue. it", "brown adipose tissue. it does", "adipose tissue. it does so", "tissue. it does so by", "it does so by promoting", "does so by promoting a", "so by promoting a leak", "by promoting a leak of", "promoting a leak of protons", "a leak of protons through", "leak of protons through the", "of protons through the mitochondrial", "protons through the mitochondrial inner", "through the mitochondrial inner membrane", "mitochondrial inner membrane which", "inner membrane which uncouples", "membrane which uncouples atp", "which uncouples atp production from", "uncouples atp production from substrate", "atp production from substrate oxidation", "from substrate oxidation leading", "substrate oxidation leading to", "oxidation leading to fast", "leading to fast oxygen consumption", "to fast oxygen consumption and", "fast oxygen consumption and ultimately", "oxygen consumption and ultimately to", "consumption and ultimately to heat", "and ultimately to heat production.", "ultimately to heat production. the", "to heat production. the thermogenic", "heat production. the thermogenic activity", "production. the thermogenic activity of", "the thermogenic activity of ucp1", "thermogenic activity of ucp1 in", "activity of ucp1 in brown", "of ucp1 in brown adipose", "ucp1 in brown adipose tissue", "in brown adipose tissue plays", "brown adipose tissue plays an", "adipose tissue plays an important", "tissue plays an important role", "plays an important role when", "an important role when the", "important role when the organism", "role when the organism needs", "when the organism needs extra", "the organism needs extra heat", "needs extra heat e.g.", "heat e.g. during", "e.g. during cold weather", "cold weather conditions for", "weather conditions for small", "conditions for small rodents", "small rodents the", "rodents the cold", "the cold stress of birth", "stress of birth or", "of birth or arousal", "birth or arousal from", "or arousal from hibernation. ucp1", "arousal from hibernation. ucp1 homologs", "from hibernation. ucp1 homologs have", "hibernation. ucp1 homologs have been", "ucp1 homologs have been found", "homologs have been found in", "have been found in lower", "been found in lower vertebrates", "found in lower vertebrates such", "in lower vertebrates such as", "lower vertebrates such as fish", "such as fish where", "as fish where their", "fish where their role", "where their role is unclear", "role is unclear cannon", "is unclear cannon &", "unclear cannon & nedergaard", "& nedergaard 2004 jastroch", "nedergaard 2004 jastroch et", "2004 jastroch et al.", "jastroch et al. 2005 .

              the", "et al. 2005 .

              the proton", "al. 2005 .

              the proton conductance", "2005 .

              the proton conductance of", ".

              the proton conductance of ucp1", "proton conductance of ucp1 in", "conductance of ucp1 in brown", "in brown adipose tissue is", "brown adipose tissue is tightly", "adipose tissue is tightly controlled.", "tissue is tightly controlled. it", "is tightly controlled. it is", "tightly controlled. it is strongly", "controlled. it is strongly inhibited", "it is strongly inhibited by", "is strongly inhibited by physiological", "strongly inhibited by physiological concentrations", "inhibited by physiological concentrations of", "by physiological concentrations of purine", "physiological concentrations of purine nucleotides.", "concentrations of purine nucleotides. this", "of purine nucleotides. this inhibition", "purine nucleotides. this inhibition is", "nucleotides. this inhibition is overcome", "this inhibition is overcome by", "inhibition is overcome by fatty", "is overcome by fatty acids", "overcome by fatty acids released", "by fatty acids released from", "fatty acids released from intracellular", "acids released from intracellular triacylglycerol", "released from intracellular triacylglycerol stores", "from intracellular triacylglycerol stores following", "intracellular triacylglycerol stores following adrenergic", "triacylglycerol stores following adrenergic activation", "stores following adrenergic activation in", "following adrenergic activation in response", "adrenergic activation in response to", "activation in response to cold", "in response to cold or", "response to cold or overfeeding.", "to cold or overfeeding. other", "cold or overfeeding. other activators", "or overfeeding. other activators include", "overfeeding. other activators include superoxide", "activators include superoxide retinoic", "include superoxide retinoic acid", "retinoic acid the retinoid", "acid the retinoid 4", "retinoid 4 e", "e 2 5", "2 5 6 7", "5 6 7 8 tetrahydro", "6 7 8 tetrahydro 5", "7 8 tetrahydro 5 5", "8 tetrahydro 5 5 8", "tetrahydro 5 5 8 8", "5 5 8 8 tetra", "5 8 8 tetra methyl", "8 8 tetra methyl 2", "8 tetra methyl 2 naphtalenyl", "methyl 2 naphtalenyl 1", "2 naphtalenyl 1 propenyl", "naphtalenyl 1 propenyl benzoic", "propenyl benzoic acid ttnpb", "acid ttnpb and", "ttnpb and reactive alkenals", "and reactive alkenals such", "reactive alkenals such as", "alkenals such as hydroxynonenal.", "such as hydroxynonenal.

              there is", "as hydroxynonenal.

              there is strong", "hydroxynonenal.

              there is strong evidence", "

              there is strong evidence that", "is strong evidence that the", "strong evidence that the regulated", "evidence that the regulated uncoupling", "that the regulated uncoupling caused", "the regulated uncoupling caused by", "regulated uncoupling caused by these", "uncoupling caused by these proteins", "caused by these proteins attenuates", "by these proteins attenuates mitochondrial", "these proteins attenuates mitochondrial reactive", "proteins attenuates mitochondrial reactive oxygen", "attenuates mitochondrial reactive oxygen species", "mitochondrial reactive oxygen species production", "oxygen species production protects", "species production protects against", "production protects against cellular", "against cellular damage and", "damage and in", "and in beta cells", "in beta cells diminishes", "beta cells diminishes insulin", "cells diminishes insulin secretion.", "diminishes insulin secretion. there are", "insulin secretion. there are also", "secretion. there are also untested", "there are also untested suggestions", "are also untested suggestions that", "also untested suggestions that their", "untested suggestions that their transport", "suggestions that their transport of", "that their transport of fatty", "their transport of fatty acids", "transport of fatty acids may", "of fatty acids may be", "fatty acids may be physiologically", "acids may be physiologically important", "be physiologically important brand", "physiologically important brand &", "important brand & esteves", "esteves 2005 esteves", "2005 esteves &", "& brand 2005 krauss", "brand 2005 krauss et", "2005 krauss et al.", "krauss et al. 2005 .", "et al. 2005 .

              ", "al. 2005 .

              several", "2005 .

              several models", ".

              several models have", "

              several models have been", "several models have been proposed", "models have been proposed for", "have been proposed for the", "been proposed for the molecular", "proposed for the molecular mechanism", "for the molecular mechanism by", "the molecular mechanism by which", "molecular mechanism by which fatty", "mechanism by which fatty acids", "by which fatty acids lead", "which fatty acids lead to", "fatty acids lead to increased", "acids lead to increased proton", "lead to increased proton conductance", "to increased proton conductance by", "increased proton conductance by ucp1", "proton conductance by ucp1 in", "conductance by ucp1 in brown", "by ucp1 in brown adipose", "in brown adipose tissue mitochondria", "brown adipose tissue mitochondria and", "adipose tissue mitochondria and presumably", "tissue mitochondria and presumably by", "mitochondria and presumably by the", "and presumably by the other", "presumably by the other ucps.", "by the other ucps. we", "the other ucps. we have", "other ucps. we have depicted", "ucps. we have depicted the", "we have depicted the most", "have depicted the most likely", "depicted the most likely model", "most likely model the", "likely model the \\fatty", "model the \\fatty acid", "the \\fatty acid cycling\\ model", "acid cycling\\ model in", "cycling\\ model in this", "model in this pathway", "in this pathway .

              studies of", "this pathway .

              studies of mouse", "pathway .

              studies of mouse models", ".

              studies of mouse models and", "of mouse models and cultured", "mouse models and cultured human", "models and cultured human cells", "and cultured human cells have", "cultured human cells have suggested", "human cells have suggested that", "cells have suggested that oleoyl", "have suggested that oleoyl phenylalanine", "that oleoyl phenylalanine synthesized", "oleoyl phenylalanine synthesized by", "phenylalanine synthesized by extracellular", "by extracellular pm20d1 may", "extracellular pm20d1 may play", "pm20d1 may play a", "may play a role in", "play a role in uncoupling", "a role in uncoupling independent", "role in uncoupling independent of", "in uncoupling independent of the", "uncoupling independent of the action", "independent of the action of", "of the action of ucps", "action of ucps long", "of ucps long et", "ucps long et al.", "long et al. 2016", "et al. 2016 .", "al. 2016 . its", "2016 . its synthesis and", ". its synthesis and hydrolysis", "its synthesis and 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              the hush", "2019 .
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              the", "margottin goguet 2019 .
              the hush", "goguet 2019 .
              the hush complex", "2019 .
              the hush complex creates", ".
              the hush complex creates repressive", "hush complex creates repressive chromatin", "complex creates repressive chromatin in", "creates repressive chromatin in two", "repressive chromatin in two ways", "in two ways reviewed", "two ways reviewed in", "ways reviewed in seczynska", "and lehner 2023 . firstly", "2023 . firstly hush", ". firstly hush can", "firstly hush can cause", "hush can cause spreading of", "can cause spreading of existing", "cause spreading of existing heterochromatin", "spreading of existing heterochromatin by", "of existing heterochromatin by binding", "existing heterochromatin by binding existing", "heterochromatin by binding existing trimethylated", "by binding existing trimethylated h3k9", "binding existing trimethylated h3k9 and", "existing trimethylated h3k9 and recruiting", "trimethylated h3k9 and recruiting setdb1", "h3k9 and recruiting setdb1 to", "and recruiting setdb1 to trimethylate", "recruiting setdb1 to trimethylate h3k9", "setdb1 to trimethylate h3k9 of", "to trimethylate h3k9 of adjacent", "trimethylate h3k9 of adjacent nucleosomes", "of adjacent nucleosomes tchasovnikarova", "adjacent nucleosomes tchasovnikarova et", "nucleosomes tchasovnikarova et al.", "tchasovnikarova et al. 2015 .", "et al. 2015 . secondly", "2015 . secondly hush", ". secondly hush can", "secondly hush can initiate", "hush can initiate heterochromatin by", "can initiate heterochromatin by binding", "initiate heterochromatin by binding nascent", "heterochromatin by binding nascent transcripts", "by binding nascent transcripts via", "binding nascent transcripts via its", "nascent transcripts via its phpln1", "transcripts via its phpln1 subunit", "via its phpln1 subunit and", "its phpln1 subunit and recruiting", "phpln1 subunit and recruiting setdb1", "subunit and recruiting setdb1 to", "recruiting setdb1 to trimethylate lysine", "setdb1 to trimethylate lysine 9", "to trimethylate lysine 9 of", "trimethylate lysine 9 of histone", "lysine 9 of histone h3", "of histone h3 h3k9", "h3 h3k9 at", "h3k9 at the locus", "at the locus being transcribed", "locus being transcribed seczynska", "being transcribed seczynska et", "transcribed seczynska et al.", "seczynska et al. 2022 .
              by", "et al. 2022 .
              by an", "al. 2022 .
              by an uncharacterized", "2022 .
              by an uncharacterized mechanism", "an uncharacterized mechanism the", "uncharacterized mechanism the hush", "mechanism the hush complex", "the hush complex targets long", "hush complex targets long intronless", "complex targets long intronless cdnas", "long intronless cdnas such", "intronless cdnas such as", "cdnas such as those", "such as those produced by", "as those produced by retroelements", "produced by retroelements as", "by retroelements as well", "retroelements as well as", "as well as unusually long", "well as unusually long exons", "as unusually long exons of", "unusually long exons of normal", "long exons of normal cellular", "exons of normal cellular genes", "normal cellular genes seczynska", "cellular genes seczynska et", "genes seczynska et al.", "seczynska et al. 2022 .", "et al. 2022 . introns", "al. 2022 . introns somehow", "2022 . introns somehow protect", ". introns somehow protect against", "introns somehow protect against silencing", "somehow protect against silencing by", "protect against silencing by hush", "silencing by hush though", "by hush though actual", "hush though actual splicing", "though actual splicing is not", "actual splicing is not required", "is not required seczynska", "not required seczynska et", "required seczynska et al.", "et al. 2022 . in", "al. 2022 . in mice", ". in mice znf638", "mice znf638 np220", "znf638 np220 znf638", "znf638 gene recruits the", "gene recruits the hush", "recruits the hush complex to", "the hush complex to unintegrated", "hush complex to unintegrated murine", "complex to unintegrated murine leukemia", "to unintegrated murine leukemia virus", "murine leukemia virus mlv", "mlv zhu et", "al. 2018 and in", "2018 and in human", "and in human cells znf638", "human cells znf638 np220", "znf638 np220 and", "np220 and hush silence", "and hush silence recombinant adeno", "hush silence recombinant adeno associated", "silence recombinant adeno associated viruses", "adeno associated viruses das", "associated viruses das et", "viruses das et al.", "das et al. 2022 .", "et al. 2022 . the", "al. 2022 . the potential", "2022 . the potential recruitment", ". the potential recruitment of", "the potential recruitment of hush", "potential recruitment of hush by", "recruitment of hush by znf638", "of hush by znf638 to", "hush by znf638 to human", "by znf638 to human retroelements", "znf638 to human retroelements is", "to human retroelements is not", "human retroelements is not yet", "retroelements is not yet demonstrated." ] }, { "record_id": "GLY_000594_1_2164", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9818564", "r hsa", "hsa 9818564", "r hsa 9818564" ] }, { "record_id": "GLY_000594_1_2164", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "epigenetic regulation", "regulation of", "of gene", "gene expression", "expression by", "by mll3", "mll3 and", "and mll4", "mll4 complexes", "epigenetic regulation of", "regulation of gene", "of gene expression", "gene expression by", "expression by mll3", "by mll3 and", "mll3 and mll4", "and mll4 complexes", "epigenetic regulation of gene", "regulation of gene expression", "of gene expression by", "gene expression by mll3", "expression by mll3 and", "by mll3 and mll4", "mll3 and mll4 complexes", "epigenetic regulation of gene expression", "regulation of gene expression by", "of gene expression by mll3", "gene expression by mll3 and", "expression by mll3 and mll4", "by mll3 and mll4 complexes", "the kmt2c", "together with", "with the", "the related", "related kmt2d", "is most", "most similar", "similar to", "to drosophila", "drosophila trr", "trithorax related", "and mediates", "mediates hitone", "hitone h3", "h3 lysine", "lysine 4", "lysine 5", "5 in", "in nascent", "nascent histone", "histone h3", "the establishment", "establishment of", "of the", "the h3k4me1", "h3k4me1 epigenetic", "epigenetic marks", "at transcription", "transcription enhancers", "enhancers throughout", "throughout the", "the human", "human genome", "for review", "please refer", "refer to", "to hu", "hu et", "et al.", "al. 2013", "piunti and", "and shilatifard", "shilatifard 2016", "klonou et", "al. 2021", "2021 .

              the", ".

              the mll3", "complexes monomethylate", "monomethylate h3k4", "h3k4 at", "with estimates", "estimates ranging", "ranging from", "from approximately", "approximately 12", "12 000", "000 to", "to over", "over 20", "20 000", "000 sites", "depending on", "on the", "the cell", "cell type", "type and", "and developmental", "developmental stage.", "stage. full", "full activation", "activation of", "expression through", "through mll3", "mll4 complex", "complex target", "target enhancers", "enhancers appears", "appears to", "to require", "require simultaneous", "simultaneous monomethylation", "monomethylation of", "of h3k4", "h3k4 by", "mll3 and/or", "and/or mll4", "and acetylation", "acetylation of", "of h3k27", "h3k27 by", "by the", "the histone", "histone acetyltransferase", "acetyltransferase p300/cbp", "recruited to", "to enhancers", "enhancers through", "through direct", "direct interactions", "interactions with", "the mll3", "mll4 complexes.", "complexes. kdm6a", "also known", "known as", "as utx", "a lysine", "lysine demethylase", "demethylase that", "that acts", "acts as", "as an", "an accessory", "accessory subunit", "subunit of", "of mll3", "facilitates h3k27", "h3k27 acetylation", "acetylation by", "by removing", "removing inhibitory", "inhibitory methyl", "methyl groups", "groups from", "from h3k27", "deposited by", "the polycomb", "polycomb repressor", "repressor prc2", "prc2 complex", "reviewed in", "in fagan", "fagan and", "and dingwall", "dingwall 2019", "2019 .

              kmt2c", "as mll3", "the catalytic", "catalytic subunit", "mll3 complex", "contains two", "two closely", "closely related", "related plant", "plant homeodomain", "zinc finger", "finger clusters", "with 6", "6 7", "7 zinc", "zinc fingers", "in the", "the n", "n terminal", "terminal region", "and a", "a single", "single phd", "phd zinc", "finger near", "near the", "the c", "c terminus", "which are", "are involved", "involved in", "in protein", "protein protein", "protein interactions.", "interactions. the", "the hmg", "hmg domain", "domain in", "in kmt2c", "kmt2c enables", "enables dna", "dna binding", "while the", "the set", "set domain", "domain provides", "provides catalytic", "catalytic activity.", "activity. kmt2c", "kmt2c possesses", "possesses multiple", "multiple nuclear", "nuclear receptor", "interaction motifs", "llxxl or", "or lxxll", "are important", "important for", "for recruitment", "recruitment of", "complex to", "to nr", "nr regulated", "regulated enhancers", "2019 .

              while", ".

              while h3k4", "h3k4 monomethylation", "monomethylation by", "complexes may", "may not", "not be", "be essential", "essential for", "for expression", "expression of", "of developmental", "developmental genes", "it is", "is likely", "likely important", "for fine", "fine tuning", "tuning of", "of transcription", "transcription levels", "levels and", "and timing", "both during", "during normal", "normal development", "development and", "and in", "in cancer.", "cancer. although", "although a", "a broad", "broad dispersion", "dispersion of", "of cancer", "cancer mutations", "mutations in", "the coding", "coding regions", "regions of", "kmt2c and", "and kmt2d", "kmt2d genes", "as well", "well as", "as the", "the presence", "presence of", "of many", "many truncating", "truncating mutations", "imply a", "a tumor", "tumor suppressor", "suppressor role", "activating mutations", "set domains", "domains have", "have also", "also been", "been reported", "suggesting that", "that a", "tumor suppressive", "suppressive vs.", "vs. oncogenic", "oncogenic role", "role is", "is context", "context dependent", ".

              kmt2c is", "is frequently", "frequently mutated", "mutated in", "cancer. kmt2c", "kmt2c may", "may be", "be important", "for driving", "driving hormone", "hormone stimulated", "stimulated proliferation", "proliferation of", "of breast", "breast cancer", "cancer cells", "cells that", "that are", "are esr1", "esr1 positive", "positive and", "and erbb2", "erbb2 negative.", "negative. in", "in mice", "simultaneous overexpression", "overexpression of", "of pik3ca", "pik3ca and", "and inactivation", "inactivation of", "kmt2c blocks", "blocks differentiation", "differentiation of", "the mammary", "mammary gland", "gland and", "and leads", "leads to", "to increased", "increased stem", "stem cell", "cell self", "self renewal", "renewal through", "through hif", "hif pathway", "pathway activation", "2019 .

              non", ".

              non small", "small cell", "cell lung", "lung cancer", "is characterized", "characterized by", "by frequent", "frequent co", "co occurrence", "occurrence of", "of mutations", "as mll4", "the mll4", "2019 .

              dna", ".

              dna damage", "damage induced", "induced transcription", "transcription of", "of tp53", "tp53 target", "target genes", "genes requires", "requires both", "both kmt2c", "and kmt2d.", "kmt2d. kmt2c", "kmt2c is", "is also", "also implicated", "implicated in", "in tp53", "tp53 dependent", "dependent dna", "dna double", "double strand", "strand break", "break repair", "repair in", "in a", "a transcription", "transcription independent", "independent manner.", "manner. ktm2c", "ktm2c and", "kmt2d contribute", "contribute to", "to maintenance", "maintenance of", "of epithelial", "epithelial cell", "cell states", "states by", "by negatively", "negatively regulating", "regulating the", "the epithelial", "epithelial to", "to mesenchymal", "mesenchymal transition.", "transition. kmt2c", "kmt2c mutations", "in lung", "lung and", "and breast", "cancer are", "are frequently", "frequently found", "found in", "the first", "first phd", "phd that", "that is", "is involved", "the interaction", "interaction with", "the bap1", "bap1 histone", "histone deubiquitinating", "deubiquitinating complex", "linked to", "to polycomb", "repressor complex", "complex dependent", "dependent gene", "gene silencing", "2019 .

              heterozygous", ".

              heterozygous germline", "germline lof", "lof mutations", "in ktm2c", "ktm2c are", "are associated", "associated with", "with kleefstra", "kleefstra syndrome", "syndrome 2", "2 and", "and autism", "autism spectrum", "spectrum disorder", "2019 .

              in", ".

              in mouse", "kmt2d are", "are implicated", "in enhancer", "enhancer priming", "priming and", "and de", "de novo", "novo enhancer", "enhancer activation", "activation during", "during embryonic", "embryonic development.", "development. this", "this function", "function is", "is not", "not essential", "for the", "the maintenance", "of cell", "cell identity", "identity and", "and self", "renewal of", "of embryonic", "embryonic stem", "stem cells", "and somatic", "somatic cells", "cells but", "but is", "is necessary", "necessary for", "for esc", "esc reprogramming", "reprogramming during", "during differentiation", "differentiation and", "and for", "for production", "production of", "of induced", "induced pluripotent", "pluripotent stem", "2019 .

              ", ".

              knockout", "knockout of", "of kmt2d", "in human", "human colon", "colon carcinoma", "carcinoma cell", "cell line", "line hct116", "which already", "already harbors", "harbors inactivating", "inactivating mutations", "in both", "both alleles", "alleles of", "of kmt2c", "to significant", "significant global", "global reduction", "reduction of", "2013 .", ". knockout", "knockout studies", "studies of", "kmt2d in", "in hct116", "hct116 cells", "cells and", "and mouse", "mouse embryonic", "embryonic fibroblasts", "implicate at", "at least", "least partially", "partially redundant", "redundant roles", "roles of", "complexes in", "in h3k4", ". genome", "genome wide", "wide chip", "chip seq", "seq analysis", "analysis in", "both hct116", "and mefs", "mefs showed", "showed that", "that ~80%", "~80% of", "mll4 peaks", "peaks are", "are enriched", "enriched at", "at intergenic", "intergenic and", "and intragenic", "intragenic regions", "while only", "only ~20%", "~20% of", "the peaks", "peaks map", "map to", "to transcription", "transcription start", "start sites", ". mll4", "mll4 binding", "binding sites", "sites at", "at sae1", "sae1 and", "and ap3b1", "ap3b1 gene", "gene loci", "loci in", "and at", "at nanog", "nanog and", "and lefty1", "lefty1 loci", "in mefs", "are co", "co occupied", "occupied by", "by enhancer", "enhancer region", "region markers", "markers h3k4me1", "and acetylated", "acetylated h3k27", ". many", "many of", "the genes", "genes associated", "with mll3/mll4", "mll3/mll4 bound", "bound enhancers", "enhancers in", "cells are", "in intracellular", "intracellular signaling", "while genes", "mll3/mll4 independent", "independent enhancers", "enhancers tend", "tend to", "to be", "be implicated", "in regulation", "2013 .

              hoxa9", "encoded by", "by a", "a target", "target gene", "gene of", "of kmt2a", "and kmt2b", "may function", "function as", "as a", "a pioneer", "pioneer factor", "factor at", "at de", "novo enhancers", "in acute", "acute myeloid", "myeloid leukemia", "and recruit", "recruit cebpa", "cebpa and", "and the", "complexes to", "enhancers of", "of leukemogenesis", "leukemogenesis promoting", "promoting genes", "sun et", "al. 2018", "2018 .

              kmt2d", ".

              kmt2d is", "in cancer", "in dhar", "dhar and", "and lee", "lee 2021", "and is", "is one", "one of", "the most", "most frequently", "mutated genes", "genes in", "in non", "non hodgkin", "hodgkin lymphoma", "such as", "as follicular", "follicular lymphoma", "lymphoma and", "and diffuse", "diffuse large", "large b", "b cell", "cell lymphoma", "where loss", "loss of", "of function", "kmt2d appears", "be an", "an early", "early event", "event that", "that cooperates", "cooperates with", "the over", "over expression", "the bcl2", "bcl2 oncogene.", "oncogene. knockout", "in mouse", "mouse b", "cell progenitors", "progenitors impairs", "impairs their", "their differentiation", "and promotes", "promotes lymphoma", "lymphoma development.", "development. kmt2d", "kmt2d lof", "lof in", "in lymphoma", "lymphoma is", "is associated", "with reduced", "reduced h3k4me1", "h3k4me1 mark", "mark at", "at enhancers", "of multiple", "multiple tumor", "suppressor genes", "2019 .

              kmt2d", ".

              kmt2d chromatin", "chromatin enrichment", "enrichment sites", "sites significantly", "significantly overlap", "overlap with", "with tp53", "tp53 binding", "binding sites.", "sites. aberrant", "aberrant transcription", "transcription associated", "tp53 mutations", "in colon", "carcinoma is", "is dependent", "dependent on", "on kmt2d", "kmt2d mediated", "mediated h3k4", "h3k4 monomethylation.", "monomethylation. kmt2d", "kmt2d can", "can be", "be inactivated", "inactivated through", "through phosphorylation", "phosphorylation by", "by sgk1", "a pi3k", "pi3k effector", "effector kinase", "kinase closely", "related to", "to akt1.", "akt1. sgk1", "sgk1 is", "is the", "the estrogen", "estrogen inducible", "inducible kinase", "whose transcription", "transcription is", "is collaboratively", "collaboratively activated", "activated by", "by esr1", "esr1 and", "kmt2d. sgk1", "sgk1 mediated", "mediated phosphorylation", "phosphorylation on", "kmt2d on", "on serine", "serine s1331", "s1331 near", "the second", "second phd", "phd results", "results in", "in downregulation", "downregulation of", "monomethylation at", "at esr1", "esr1 target", "thus constituting", "constituting a", "a negative", "negative feedback", "feedback loop", "in kmt2d", "with kabuki", "kabuki syndrome", "syndrome 1.", "1. kabuki", "syndrome patients", "patients have", "have a", "a modestly", "modestly increased", "increased predisposition", "predisposition to", "to cancer", "in particular", "particular lymphoma", "wilms tumor", "synovial sarcoma", "sarcoma and", "and neuroblastoma.", "neuroblastoma. mice", "mice with", "with brain", "brain specific", "specific knockout", "develop medulloblastoma", "medulloblastoma that", "that shows", "shows hyperactivation", "hyperactivation of", "of ras", "ras and", "and notch", "notch signaling", "2019 .

              based", ".

              based on", "on mouse", "mouse studies", "complexes play", "play an", "an important", "important role", "role in", "in adipogenesis", "adipogenesis and", "and myogenesis.", "myogenesis. kmt2c", "kmt2c ko", "ko mice", "mice die", "die around", "around birth", "birth with", "with no", "no obvious", "obvious morphological", "morphological abnormalities", "abnormalities in", "in embryonic", "embryonic development", "while kmt2d", "kmt2d ko", "mice show", "show early", "early embryonic", "embryonic lethality", "lethality around", "around e9.5", "lee et", ". pups", "pups with", "with kmt2d", "ko in", "in precursors", "precursors of", "of brown", "brown preadipocytes", "preadipocytes and", "and skeletal", "skeletal myocytes", "myocytes are", "are obtained", "obtained at", "at the", "the expected", "expected mendelian", "mendelian ratio", "ratio but", "but display", "display marked", "marked reduction", "reduction in", "in back", "back muscles", "muscles and", "and die", "die immediately", "immediately after", "after birth", "birth due", "due to", "to breathing", "breathing malfunction", "also showing", "showing a", "a decrease", "decrease in", "in brown", "brown adipose", "adipose tissue", "tissue mass", ". in", "in cultured", "cultured mouse", "mouse brown", "ko of", "kmt2d leads", "to a", "a moderate", "moderate differentiation", "differentiation defect", "defect along", "along with", "with a", "a transient", "transient up", "up regulation", "kmt2c expression", "whereas ko", "kmt2c has", "has no", "no effect", "effect on", "on adipogenesis", "suggesting a", "a more", "more prominent", "prominent role", "role of", "in development", "a partial", "partial compensation", "compensation of", "kmt2d loss", "loss by", "by kmt2c", ". ko", "kmt2d 3t3", "3t3 l1", "l1 mouse", "mouse white", "white preadipocytes", "preadipocytes inhibits", "inhibits adipogenesis", "and kmt2c", "are also", "also required", "required for", "for adipogenesis", "adipogenesis in", ". by", "by chip", "the average", "average length", "length of", "kmt2d binding", "binding regions", "regions is", "is between", "between 350", "350 and", "and 400", "400 bp", "the binding", "regions change", "change dramatically", "dramatically from", "from the", "the preadipocytes", "preadipocytes stage", "stage to", "to the", "the onset", "onset of", "of adipogenesis", "but are", "are then", "then kmt2d", "regions were", "were largely", "largely non", "non overlapping", "overlapping between", "between brown", "brown adipocytes", "adipocytes and", "kmt2c mll3", "complex together", "together with the", "with the related", "the related kmt2d", "kmt2d mll4", "complex is", "is most similar", "most similar to", "similar to drosophila", "to drosophila trr", "trr trithorax", "related and", "and mediates hitone", "mediates hitone h3", "hitone h3 lysine", "h3 lysine 4", "4 h3k4", "lysine 5 in", "5 in nascent", "in nascent histone", "nascent histone h3", "h3 monomethylation", "monomethylation with", "with the establishment", "the establishment of", "establishment of the", "of the h3k4me1", "the h3k4me1 epigenetic", "h3k4me1 epigenetic marks", "marks at", "at transcription enhancers", "transcription enhancers throughout", "enhancers throughout the", "throughout the human", "the human genome", "genome for", "review please", "please refer to", "refer to hu", "to hu et", "hu et al.", "et al. 2013", "2013 piunti", "piunti and shilatifard", "and shilatifard 2016", "2016 klonou", "klonou et al.", "et al. 2021", "al. 2021 .

              the", "2021 .

              the mll3", ".

              the mll3 and", "mll4 complexes monomethylate", "complexes monomethylate h3k4", "monomethylate h3k4 at", "h3k4 at transcription", "genome with", "with estimates ranging", "estimates ranging from", "ranging from approximately", "from approximately 12", "approximately 12 000", "12 000 to", "000 to over", "to over 20", "over 20 000", "20 000 sites", "sites depending", "depending on the", "on the cell", "the cell type", "cell type and", "type and developmental", "and developmental stage.", "developmental stage. full", "stage. full activation", "full activation of", "activation of gene", "gene expression through", "expression through mll3", "through mll3 and", "and mll4 complex", "mll4 complex target", "complex target enhancers", "target enhancers appears", "enhancers appears to", "appears to require", "to require simultaneous", "require simultaneous monomethylation", "simultaneous monomethylation of", "monomethylation of h3k4", "of h3k4 by", "h3k4 by mll3", "by mll3 and/or", "mll3 and/or mll4", "and/or mll4 complexes", "complexes and", "and acetylation of", "acetylation of h3k27", "of h3k27 by", "h3k27 by the", "by the histone", "the histone acetyltransferase", "histone acetyltransferase p300/cbp", "p300/cbp recruited", "recruited to enhancers", "to enhancers through", "enhancers through direct", "through direct interactions", "direct interactions with", "interactions with the", "with the mll3", "the mll3 and", "and mll4 complexes.", "mll4 complexes. kdm6a", "kdm6a also", "also known as", "known as utx", "a lysine demethylase", "lysine demethylase that", "demethylase that acts", "that acts as", "acts as an", "as an accessory", "an accessory subunit", "accessory subunit of", "subunit of mll3", "of mll3 and", "complexes facilitates", "facilitates h3k27 acetylation", "h3k27 acetylation by", "acetylation by removing", "by removing inhibitory", "removing inhibitory methyl", "inhibitory methyl groups", "methyl groups from", "groups from h3k27", "h3k27 deposited", "deposited by the", "by the polycomb", "the polycomb repressor", "polycomb repressor prc2", "repressor prc2 complex", "complex reviewed", "reviewed in fagan", "in fagan and", "fagan and dingwall", "and dingwall 2019", "dingwall 2019 .

              kmt2c", ".

              kmt2c also", "known as mll3", "the catalytic subunit", "catalytic subunit of", "subunit of the", "of the mll3", "the mll3 complex", "complex contains", "contains two closely", "two closely related", "closely related plant", "related plant homeodomain", "homeodomain phd", "zinc finger clusters", "clusters with", "with 6 7", "6 7 zinc", "7 zinc fingers", "fingers in", "in the n", "the n terminal", "n terminal region", "region and", "and a single", "a single phd", "single phd zinc", "phd zinc finger", "zinc finger near", "finger near the", "near the c", "the c terminus", "terminus which", "which are involved", "are involved in", "involved in protein", "in protein protein", "protein protein interactions.", "protein interactions. the", "interactions. the hmg", "the hmg domain", "hmg domain in", "domain in kmt2c", "in kmt2c enables", "kmt2c enables dna", "enables dna binding", "binding while", "while the set", "the set domain", "set domain provides", "domain provides catalytic", "provides catalytic activity.", "catalytic activity. kmt2c", "activity. kmt2c possesses", "kmt2c possesses multiple", "possesses multiple nuclear", "multiple nuclear receptor", "receptor nr", "nr interaction", "motifs llxxl", "llxxl or lxxll", "which are important", "are important for", "important for recruitment", "for recruitment of", "recruitment of the", "mll3 complex to", "complex to nr", "to nr regulated", "nr regulated enhancers", "enhancers reviewed", "dingwall 2019 .

              while", "2019 .

              while h3k4", ".

              while h3k4 monomethylation", "h3k4 monomethylation by", "monomethylation by mll3", "mll4 complexes may", "complexes may not", "may not be", "not be essential", "be essential for", "essential for expression", "for expression of", "expression of developmental", "of developmental genes", "genes it", "it is likely", "is likely important", "likely important for", "important for fine", "for fine tuning", "fine tuning of", "tuning of transcription", "of transcription levels", "transcription levels and", "levels and timing", "timing both", "both during normal", "during normal development", "normal development and", "development and in", "and in cancer.", "in cancer. although", "cancer. although a", "although a broad", "a broad dispersion", "broad dispersion of", "dispersion of cancer", "of cancer mutations", "cancer mutations in", "mutations in the", "in the coding", "the coding regions", "coding regions of", "regions of the", "of the kmt2c", "the kmt2c and", "kmt2c and kmt2d", "and kmt2d genes", "genes as", "as well as", "well as the", "as the presence", "the presence of", "presence of many", "of many truncating", "many truncating mutations", "mutations imply", "imply a tumor", "a tumor suppressor", "tumor suppressor role", "role activating", "activating mutations in", "in the set", "the set domains", "set domains have", "domains have also", "have also been", "also been reported", "reported suggesting", "suggesting that a", "that a tumor", "a tumor suppressive", "tumor suppressive vs.", "suppressive vs. oncogenic", "vs. oncogenic role", "oncogenic role is", "role is context", "is context dependent", "dependent reviewed", "2019 .

              kmt2c is", ".

              kmt2c is frequently", "is frequently mutated", "frequently mutated in", "mutated in cancer.", "in cancer. kmt2c", "cancer. kmt2c may", "kmt2c may be", "may be important", "be important for", "important for driving", "for driving hormone", "driving hormone stimulated", "hormone stimulated proliferation", "stimulated proliferation of", "proliferation of breast", "of breast cancer", "breast cancer cells", "cancer cells that", "cells that are", "that are esr1", "are esr1 positive", "esr1 positive and", "positive and erbb2", "and erbb2 negative.", "erbb2 negative. in", "negative. in mice", "mice simultaneous", "simultaneous overexpression of", "overexpression of pik3ca", "of pik3ca and", "pik3ca and inactivation", "and inactivation of", "inactivation of the", "the kmt2c blocks", "kmt2c blocks differentiation", "blocks differentiation of", "differentiation of the", "of the mammary", "the mammary gland", "mammary gland and", "gland and leads", "and leads to", "leads to increased", "to increased stem", "increased stem cell", "stem cell self", "cell self renewal", "self renewal through", "renewal through hif", "through hif pathway", "hif pathway activation", "activation reviewed", "dingwall 2019 .

              non", "2019 .

              non small", ".

              non small cell", "small cell lung", "cell lung cancer", "cancer nsclc", "nsclc is", "is characterized by", "characterized by frequent", "by frequent co", "frequent co occurrence", "co occurrence of", "occurrence of mutations", "of mutations in", "mutations in kmt2c", "in kmt2c and", "kmt2d also", "known as mll4", "mll4 the", "of the mll4", "the mll4 complex", "dingwall 2019 .

              dna", "2019 .

              dna damage", ".

              dna damage induced", "damage induced transcription", "induced transcription of", "transcription of tp53", "of tp53 target", "tp53 target genes", "target genes requires", "genes requires both", "requires both kmt2c", "both kmt2c and", "kmt2c and kmt2d.", "and kmt2d. kmt2c", "kmt2d. kmt2c is", "kmt2c is also", "is also implicated", "also implicated in", "implicated in tp53", "in tp53 dependent", "tp53 dependent dna", "dependent dna double", "dna double strand", "double strand break", "strand break repair", "break repair in", "repair in a", "in a transcription", "a transcription independent", "transcription independent manner.", "independent manner. ktm2c", "manner. ktm2c and", "ktm2c and kmt2d", "and kmt2d contribute", "kmt2d contribute to", "contribute to maintenance", "to maintenance of", "maintenance of epithelial", "of epithelial cell", "epithelial cell states", "cell states by", "states by negatively", "by negatively regulating", "negatively regulating the", "regulating the epithelial", "the epithelial to", "epithelial to mesenchymal", "to mesenchymal transition.", "mesenchymal transition. kmt2c", "transition. kmt2c mutations", "kmt2c mutations in", "mutations in lung", "in lung and", "lung and breast", "and breast cancer", "breast cancer are", "cancer are frequently", "are frequently found", "frequently found in", "found in the", "in the first", "the first phd", "first phd that", "phd that is", "that is involved", "is involved in", "involved in the", "in the interaction", "the interaction with", "interaction with the", "with the bap1", "the bap1 histone", "bap1 histone deubiquitinating", "histone deubiquitinating complex", "complex linked", "linked to polycomb", "to polycomb repressor", "polycomb repressor complex", "repressor complex dependent", "complex dependent gene", "dependent gene silencing", "silencing reviewed", "dingwall 2019 .

              heterozygous", "2019 .

              heterozygous germline", ".

              heterozygous germline lof", "germline lof mutations", "lof mutations in", "mutations in ktm2c", "in ktm2c are", "ktm2c are associated", "are associated with", "associated with kleefstra", "with kleefstra syndrome", "kleefstra syndrome 2", "syndrome 2 and", "2 and autism", "and autism spectrum", "autism spectrum disorder", "disorder reviewed", "dingwall 2019 .

              in", "2019 .

              in mouse", "mouse kmt2c", "and kmt2d are", "kmt2d are implicated", "are implicated in", "implicated in enhancer", "in enhancer priming", "enhancer priming and", "priming and de", "and de novo", "de novo enhancer", "novo enhancer activation", "enhancer activation during", "activation during embryonic", "during embryonic development.", "embryonic development. this", "development. this function", "this function is", "function is not", "is not essential", "not essential for", "essential for the", "for the maintenance", "the maintenance of", "maintenance of cell", "of cell identity", "cell identity and", "identity and self", "and self renewal", "self renewal of", "renewal of embryonic", "of embryonic stem", "embryonic stem cells", "cells escs", "escs and", "and somatic cells", "somatic cells but", "cells but is", "but is necessary", "is necessary for", "necessary for esc", "for esc reprogramming", "esc reprogramming during", "reprogramming during differentiation", "during differentiation and", "differentiation and for", "and for production", "for production of", "production of induced", "of induced pluripotent", "induced pluripotent stem", "pluripotent stem cells", "cells ipscs", "dingwall 2019 .

              ", "2019 .

              knockout", ".

              knockout of", "knockout of kmt2d", "kmt2d the", "complex in", "in human colon", "human colon carcinoma", "colon carcinoma cell", "carcinoma cell line", "cell line hct116", "hct116 which", "which already harbors", "already harbors inactivating", "harbors inactivating mutations", "inactivating mutations in", "mutations in both", "in both alleles", "both alleles of", "alleles of kmt2c", "kmt2c the", "leads to significant", "to significant global", "significant global reduction", "global reduction of", "reduction of h3k4", "of h3k4 monomethylation", "monomethylation hu", "al. 2013 .", "2013 . knockout", ". knockout studies", "knockout studies of", "studies of kmt2c", "of kmt2c and", "and kmt2d in", "kmt2d in hct116", "in hct116 cells", "hct116 cells and", "cells and mouse", "and mouse embryonic", "mouse embryonic fibroblasts", "fibroblasts mefs", "mefs implicate", "implicate at least", "at least partially", "least partially redundant", "partially redundant roles", "redundant roles of", "roles of mll3", "mll4 complexes in", "complexes in h3k4", "in h3k4 monomethylation", "2013 . genome", ". genome wide", "genome wide chip", "wide chip seq", "chip seq analysis", "seq analysis in", "analysis in both", "in both hct116", "both hct116 cells", "cells and mefs", "and mefs showed", "mefs showed that", "showed that ~80%", "that ~80% of", "~80% of the", "the mll4 peaks", "mll4 peaks are", "peaks are enriched", "are enriched at", "enriched at intergenic", "at intergenic and", "intergenic and intragenic", "and intragenic regions", "regions while", "while only ~20%", "only ~20% of", "~20% of the", "of the peaks", "the peaks map", "peaks map to", "map to transcription", "to transcription start", "transcription start sites", "sites tss", "2013 . mll4", ". mll4 binding", "mll4 binding sites", "binding sites at", "sites at sae1", "at sae1 and", "sae1 and ap3b1", "and ap3b1 gene", "ap3b1 gene loci", "gene loci in", "loci in hct116", "and at nanog", "at nanog and", "nanog and lefty1", "and lefty1 loci", "lefty1 loci in", "loci in mefs", "mefs are", "are co occupied", "co occupied by", "occupied by enhancer", "by enhancer region", "enhancer region markers", "region markers h3k4me1", "h3k4me1 ep300", "ep300 and", "and acetylated h3k27", "h3k27 hu", "2013 . many", ". many of", "many of the", "of the genes", "the genes associated", "genes associated with", "associated with mll3/mll4", "with mll3/mll4 bound", "mll3/mll4 bound enhancers", "bound enhancers in", "enhancers in hct116", "hct116 cells are", "cells are implicated", "implicated in intracellular", "in intracellular signaling", "signaling while", "while genes associated", "with mll3/mll4 independent", "mll3/mll4 independent enhancers", "independent enhancers tend", "enhancers tend to", "tend to be", "to be implicated", "be implicated in", "implicated in regulation", "in regulation of", "expression hu", "al. 2013 .

              hoxa9", ".

              hoxa9 encoded", "encoded by a", "by a target", "a target gene", "target gene of", "gene of kmt2a", "kmt2a mll1", "mll1 and", "kmt2b mll2", "mll2 complexes", "may function as", "function as a", "as a pioneer", "a pioneer factor", "pioneer factor at", "factor at de", "at de novo", "de novo enhancers", "novo enhancers in", "enhancers in acute", "in acute myeloid", "acute myeloid leukemia", "leukemia aml", "aml and", "and recruit cebpa", "recruit cebpa and", "cebpa and the", "and the mll3", "mll4 complexes to", "complexes to enhancers", "to enhancers of", "enhancers of leukemogenesis", "of leukemogenesis promoting", "leukemogenesis promoting genes", "genes sun", "sun et al.", "et al. 2018", "al. 2018 .

              kmt2d", "2018 .

              kmt2d is", ".

              kmt2d is frequently", "mutated in cancer", "cancer reviewed", "reviewed in dhar", "in dhar and", "dhar and lee", "and lee 2021", "2021 and", "and is one", "is one of", "one of the", "of the most", "the most frequently", "most frequently mutated", "frequently mutated genes", "mutated genes in", "genes in non", "in non hodgkin", "non hodgkin lymphoma", "lymphoma such", "such as follicular", "as follicular lymphoma", "follicular lymphoma and", "lymphoma and diffuse", "and diffuse large", "diffuse large b", "large b cell", "b cell lymphoma", "lymphoma where", "where loss of", "loss of function", "function lof", "lof of", "of kmt2d appears", "kmt2d appears to", "appears to be", "to be an", "be an early", "an early event", "early event that", "event that cooperates", "that cooperates with", "cooperates with the", "with the over", "the over expression", "over expression of", "expression of the", "of the bcl2", "the bcl2 oncogene.", "bcl2 oncogene. knockout", "oncogene. knockout of", "of kmt2d in", "kmt2d in mouse", "in mouse b", "mouse b cell", "b cell progenitors", "cell progenitors impairs", "progenitors impairs their", "impairs their differentiation", "their differentiation and", "differentiation and promotes", "and promotes lymphoma", "promotes lymphoma development.", "lymphoma development. kmt2d", "development. kmt2d lof", "kmt2d lof in", "lof in lymphoma", "in lymphoma is", "lymphoma is associated", "is associated with", "associated with reduced", "with reduced h3k4me1", "reduced h3k4me1 mark", "h3k4me1 mark at", "mark at enhancers", "at enhancers of", "enhancers of multiple", "of multiple tumor", "multiple tumor suppressor", "tumor suppressor genes", "genes reviewed", "dingwall 2019 .

              kmt2d", "2019 .

              kmt2d chromatin", ".

              kmt2d chromatin enrichment", "chromatin enrichment sites", "enrichment sites significantly", "sites significantly overlap", "significantly overlap with", "overlap with tp53", "with tp53 binding", "tp53 binding sites.", "binding sites. aberrant", "sites. aberrant transcription", "aberrant transcription associated", "transcription associated with", "associated with tp53", "with tp53 mutations", "tp53 mutations in", "mutations in colon", "in colon carcinoma", "colon carcinoma is", "carcinoma is dependent", "is dependent on", "dependent on kmt2d", "on kmt2d mediated", "kmt2d mediated h3k4", "mediated h3k4 monomethylation.", "h3k4 monomethylation. kmt2d", "monomethylation. kmt2d can", "kmt2d can be", "can be inactivated", "be inactivated through", "inactivated through phosphorylation", "through phosphorylation by", "phosphorylation by sgk1", "sgk1 a", "a pi3k effector", "pi3k effector kinase", "effector kinase closely", "kinase closely related", "closely related to", "related to akt1.", "to akt1. sgk1", "akt1. sgk1 is", "sgk1 is the", "is the estrogen", "the estrogen inducible", "estrogen inducible kinase", "kinase whose", "whose transcription is", "transcription is collaboratively", "is collaboratively activated", "collaboratively activated by", "activated by esr1", "by esr1 and", "esr1 and kmt2d.", "and kmt2d. sgk1", "kmt2d. sgk1 mediated", "sgk1 mediated phosphorylation", "mediated phosphorylation on", "phosphorylation on kmt2d", "on kmt2d on", "kmt2d on serine", "on serine s1331", "serine s1331 near", "s1331 near the", "near the second", "the second phd", "second phd results", "phd results in", "results in downregulation", "in downregulation of", "downregulation of h3k4", "h3k4 monomethylation at", "monomethylation at esr1", "at esr1 target", "esr1 target genes", "genes thus", "thus constituting a", "constituting a negative", "a negative feedback", "negative feedback loop", "loop reviewed", "mutations in kmt2d", "in kmt2d are", "kmt2d are associated", "associated with kabuki", "with kabuki syndrome", "kabuki syndrome 1.", "syndrome 1. kabuki", "1. kabuki syndrome", "kabuki syndrome patients", "syndrome patients have", "patients have a", "have a modestly", "a modestly increased", "modestly increased predisposition", "increased predisposition to", "predisposition to cancer", "cancer in", "in particular lymphoma", "lymphoma wilms", "tumor hepatoblastoma", "hepatoblastoma synovial", "synovial sarcoma and", "sarcoma and neuroblastoma.", "and neuroblastoma. mice", "neuroblastoma. mice with", "mice with brain", "with brain specific", "brain specific knockout", "specific knockout of", "mll4 develop", "develop medulloblastoma that", "medulloblastoma that shows", "that shows hyperactivation", "shows hyperactivation of", "hyperactivation of ras", "of ras and", "ras and notch", "and notch signaling", "signaling reviewed", "dingwall 2019 .

              based", "2019 .

              based on", ".

              based on mouse", "on mouse studies", "studies mll3", "mll4 complexes play", "complexes play an", "play an important", "an important role", "important role in", "role in adipogenesis", "in adipogenesis and", "adipogenesis and myogenesis.", "and myogenesis. kmt2c", "myogenesis. kmt2c ko", "kmt2c ko mice", "ko mice die", "mice die around", "die around birth", "around birth with", "birth with no", "with no obvious", "no obvious morphological", "obvious morphological abnormalities", "morphological abnormalities in", "abnormalities in embryonic", "in embryonic development", "development while", "while kmt2d ko", "kmt2d ko mice", "ko mice show", "mice show early", "show early embryonic", "early embryonic lethality", "embryonic lethality around", "lethality around e9.5", "e9.5 lee", "lee et al.", "2013 . pups", ". pups with", "pups with kmt2d", "with kmt2d ko", "kmt2d ko in", "ko in precursors", "in precursors of", "precursors of brown", "of brown preadipocytes", "brown preadipocytes and", "preadipocytes and skeletal", "and skeletal myocytes", "skeletal myocytes are", "myocytes are obtained", "are obtained at", "obtained at the", "at the expected", "the expected mendelian", "expected mendelian ratio", "mendelian ratio but", "ratio but display", "but display marked", "display marked reduction", "marked reduction in", "reduction in back", "in back muscles", "back muscles and", "muscles and die", "and die immediately", "die immediately after", "immediately after birth", "after birth due", "birth due to", "due to breathing", "to breathing malfunction", "malfunction also", "also showing a", "showing a decrease", "a decrease in", "decrease in brown", "in brown adipose", "brown adipose tissue", "adipose tissue mass", "mass lee", "2013 . in", ". in cultured", "in cultured mouse", "cultured mouse brown", "mouse brown preadipocytes", "preadipocytes ko", "ko of kmt2d", "of kmt2d leads", "kmt2d leads to", "leads to a", "to a moderate", "a moderate differentiation", "moderate differentiation defect", "differentiation defect along", "defect along with", "along with a", "with a transient", "a transient up", "transient up regulation", "up regulation of", "regulation of kmt2c", "of kmt2c expression", "expression whereas", "whereas ko of", "ko of kmt2c", "of kmt2c has", "kmt2c has no", "has no effect", "no effect on", "effect on adipogenesis", "adipogenesis suggesting", "suggesting a more", "a more prominent", "more prominent role", "prominent role of", "role of kmt2d", "kmt2d in development", "in development and", "development and a", "and a partial", "a partial compensation", "partial compensation of", "compensation of kmt2d", "of kmt2d loss", "kmt2d loss by", "loss by kmt2c", "kmt2c lee", "2013 . ko", ". ko of", "of kmt2d 3t3", "kmt2d 3t3 l1", "3t3 l1 mouse", "l1 mouse white", "mouse white preadipocytes", "white preadipocytes inhibits", "preadipocytes inhibits adipogenesis", "and kmt2c and", "kmt2d are also", "are also required", "also required for", "required for adipogenesis", "for adipogenesis in", "adipogenesis in mouse", "in mouse embryonic", "fibroblasts lee", "2013 . by", ". by chip", "by chip seq", "seq the", "the average length", "average length of", "length of kmt2d", "of kmt2d binding", "kmt2d binding regions", "binding regions is", "regions is between", "is between 350", "between 350 and", "350 and 400", "and 400 bp", "bp and", "and the binding", "the binding regions", "binding regions change", "regions change dramatically", "change dramatically from", "dramatically from the", "from the preadipocytes", "the preadipocytes stage", "preadipocytes stage to", "stage to the", "to the onset", "the onset of", "onset of adipogenesis", "adipogenesis but", "but are then", "are then kmt2d", "then kmt2d binding", "binding regions were", "regions were largely", "were largely non", "largely non overlapping", "non overlapping between", "overlapping between brown", "between brown adipocytes", "brown adipocytes and", "adipocytes and skeletal", "myocytes lee", "the kmt2c mll3", "complex together with", "together with the related", "with the related kmt2d", "related kmt2d mll4", "complex is most", "is most similar to", "most similar to drosophila", "similar to drosophila trr", "drosophila trr trithorax", "trr trithorax related", "trithorax related and", "related and mediates", "and mediates hitone h3", "mediates hitone h3 lysine", "hitone h3 lysine 4", "lysine 4 h3k4", "h3k4 lysine", "lysine 5 in nascent", "5 in nascent histone", "in nascent histone h3", "histone h3 monomethylation", "monomethylation with the", "with the establishment of", "the establishment of the", "establishment of the h3k4me1", "of the h3k4me1 epigenetic", "the h3k4me1 epigenetic marks", "epigenetic marks at", "marks at transcription", "at transcription enhancers throughout", "transcription enhancers throughout the", "enhancers throughout the human", "throughout the human genome", "human genome for", "genome for review", "for review please", "review please refer", "please refer to hu", "refer to hu et", "to hu et al.", "hu et al. 2013", "al. 2013 piunti", "2013 piunti and", "piunti and shilatifard 2016", "shilatifard 2016 klonou", "2016 klonou et", "klonou et al. 2021", "et al. 2021 .

              the", "al. 2021 .

              the mll3", "2021 .

              the mll3 and", ".

              the mll3 and mll4", "and mll4 complexes monomethylate", "mll4 complexes monomethylate h3k4", "complexes monomethylate h3k4 at", "monomethylate h3k4 at transcription", "h3k4 at transcription enhancers", "human genome with", "genome with estimates", "with estimates ranging from", "estimates ranging from approximately", "ranging from approximately 12", "from approximately 12 000", "approximately 12 000 to", "12 000 to over", "000 to over 20", "to over 20 000", "over 20 000 sites", "000 sites depending", "sites depending on", "depending on the cell", "on the cell type", "the cell type and", "cell type and developmental", "type and developmental stage.", "and developmental stage. full", "developmental stage. full activation", "stage. full activation of", "full activation of gene", "activation of gene expression", "of gene expression through", "gene expression through mll3", "expression through mll3 and", "through mll3 and mll4", "mll3 and mll4 complex", "and mll4 complex target", "mll4 complex target enhancers", "complex target enhancers appears", "target enhancers appears to", "enhancers appears to require", "appears to require simultaneous", "to require simultaneous monomethylation", "require simultaneous monomethylation of", "simultaneous monomethylation of h3k4", "monomethylation of h3k4 by", "of h3k4 by mll3", "h3k4 by mll3 and/or", "by mll3 and/or mll4", "mll3 and/or mll4 complexes", "mll4 complexes and", "complexes and acetylation", "and acetylation of h3k27", "acetylation of h3k27 by", "of h3k27 by the", "h3k27 by the histone", "by the histone acetyltransferase", "the histone acetyltransferase p300/cbp", "acetyltransferase p300/cbp recruited", "p300/cbp recruited to", "recruited to enhancers through", "to enhancers through direct", "enhancers through direct interactions", "through direct interactions with", "direct interactions with the", "interactions with the mll3", "with the mll3 and", "the mll3 and mll4", "mll3 and mll4 complexes.", "and mll4 complexes. kdm6a", "complexes. kdm6a also", "kdm6a also known", "also known as utx", "utx a", "a lysine demethylase that", "lysine demethylase that acts", "demethylase that acts as", "that acts as an", "acts as an accessory", "as an accessory subunit", "an accessory subunit of", "accessory subunit of mll3", "subunit of mll3 and", "of mll3 and mll4", "mll4 complexes facilitates", "complexes facilitates h3k27", "facilitates h3k27 acetylation by", "h3k27 acetylation by removing", "acetylation by removing inhibitory", "by removing inhibitory methyl", "removing inhibitory methyl groups", "inhibitory methyl groups from", "methyl groups from h3k27", "from h3k27 deposited", "h3k27 deposited by", "deposited by the polycomb", "by the polycomb repressor", "the polycomb repressor prc2", "polycomb repressor prc2 complex", "prc2 complex reviewed", "complex reviewed in", "reviewed in fagan and", "in fagan and dingwall", "fagan and dingwall 2019", "and dingwall 2019 .

              kmt2c", "2019 .

              kmt2c also", ".

              kmt2c also known", "also known as mll3", "mll3 the", "the catalytic subunit of", "catalytic subunit of the", "subunit of the mll3", "of the mll3 complex", "mll3 complex contains", "complex contains two", "contains two closely related", "two closely related plant", "closely related plant homeodomain", "plant homeodomain phd", "finger clusters with", "clusters with 6", "with 6 7 zinc", "6 7 zinc fingers", "zinc fingers in", "fingers in the", "in the n terminal", "the n terminal region", "terminal region and", "region and a", "and a single phd", "a single phd zinc", "single phd zinc finger", "phd zinc finger near", "zinc finger near the", "finger near the c", "near the c terminus", "c terminus which", "terminus which are", "which are involved in", "are involved in protein", "involved in protein protein", "in protein protein interactions.", "protein protein interactions. the", "protein interactions. the hmg", "interactions. the hmg domain", "the hmg domain in", "hmg domain in kmt2c", "domain in kmt2c enables", "in kmt2c enables dna", "kmt2c enables dna binding", "dna binding while", "binding while the", "while the set domain", "the set domain provides", "set domain provides catalytic", "domain provides catalytic activity.", "provides catalytic activity. kmt2c", "catalytic activity. kmt2c possesses", "activity. kmt2c possesses multiple", "kmt2c possesses multiple nuclear", "possesses multiple nuclear receptor", "nuclear receptor nr", "nr interaction motifs", "interaction motifs llxxl", "motifs llxxl or", "lxxll which", "which are important for", "are important for recruitment", "important for recruitment of", "for recruitment of the", "recruitment of the mll3", "the mll3 complex to", "mll3 complex to nr", "complex to nr regulated", "to nr regulated enhancers", "regulated enhancers reviewed", "enhancers reviewed in", "and dingwall 2019 .

              while", "dingwall 2019 .

              while h3k4", "2019 .

              while h3k4 monomethylation", ".

              while h3k4 monomethylation by", "h3k4 monomethylation by mll3", "monomethylation by mll3 and", "and mll4 complexes may", "mll4 complexes may not", "complexes may not be", "may not be essential", "not be essential for", "be essential for expression", "essential for expression of", "for expression of developmental", "expression of developmental genes", "developmental genes it", "genes it is", "it is likely important", "is likely important for", "likely important for fine", "important for fine tuning", "for fine tuning of", "fine tuning of transcription", "tuning of transcription levels", "of transcription levels and", "transcription levels and timing", "and timing both", "timing both during", "both during normal development", "during normal development and", "normal development and in", "development and in cancer.", "and in cancer. although", "in cancer. although a", "cancer. although a broad", "although a broad dispersion", "a broad dispersion of", "broad dispersion of cancer", "dispersion of cancer mutations", "of cancer mutations in", "cancer mutations in the", "mutations in the coding", "in the coding regions", "the coding regions of", "coding regions of the", "regions of the kmt2c", "of the kmt2c and", "the kmt2c and kmt2d", "kmt2c and kmt2d genes", "kmt2d genes as", "genes as well", "as well as the", "well as the presence", "as the presence of", "the presence of many", "presence of many truncating", "of many truncating mutations", "truncating mutations imply", "mutations imply a", "imply a tumor suppressor", "a tumor suppressor role", "suppressor role activating", "role activating mutations", "activating mutations in the", "mutations in the set", "in the set domains", "the set domains have", "set domains have also", "domains have also been", "have also been reported", "been reported suggesting", "reported suggesting that", "suggesting that a tumor", "that a tumor suppressive", "a tumor suppressive vs.", "tumor suppressive vs. oncogenic", "suppressive vs. oncogenic role", "vs. oncogenic role is", "oncogenic role is context", "role is context dependent", "context dependent reviewed", "dependent reviewed in", "dingwall 2019 .

              kmt2c is", "2019 .

              kmt2c is frequently", ".

              kmt2c is frequently mutated", "is frequently mutated in", "frequently mutated in cancer.", "mutated in cancer. kmt2c", "in cancer. kmt2c may", "cancer. kmt2c may be", "kmt2c may be important", "may be important for", "be important for driving", "important for driving hormone", "for driving hormone stimulated", "driving hormone stimulated proliferation", "hormone stimulated proliferation of", "stimulated proliferation of breast", "proliferation of breast cancer", "of breast cancer cells", "breast cancer cells that", "cancer cells that are", "cells that are esr1", "that are esr1 positive", "are esr1 positive and", "esr1 positive and erbb2", "positive and erbb2 negative.", "and erbb2 negative. in", "erbb2 negative. in mice", "in mice simultaneous", "mice simultaneous overexpression", "simultaneous overexpression of pik3ca", "overexpression of pik3ca and", "of pik3ca and inactivation", "pik3ca and inactivation of", "and inactivation of the", "inactivation of the kmt2c", "of the kmt2c blocks", "the kmt2c blocks differentiation", "kmt2c blocks differentiation of", "blocks differentiation of the", "differentiation of the mammary", "of the mammary gland", "the mammary gland and", "mammary gland and leads", "gland and leads to", "and leads to increased", "leads to increased stem", "to increased stem cell", "increased stem cell self", "stem cell self renewal", "cell self renewal through", "self renewal through hif", "renewal through hif pathway", "through hif pathway activation", "pathway activation reviewed", "activation reviewed in", "and dingwall 2019 .

              non", "dingwall 2019 .

              non small", "2019 .

              non small cell", ".

              non small cell lung", "small cell lung cancer", "lung cancer nsclc", "nsclc is characterized", "is characterized by frequent", "characterized by frequent co", "by frequent co occurrence", "frequent co occurrence of", "co occurrence of mutations", "occurrence of mutations in", "of mutations in kmt2c", "mutations in kmt2c and", "in kmt2c and kmt2d", "and kmt2d also", "kmt2d also known", "also known as mll4", "as mll4 the", "mll4 the catalytic", "subunit of the mll4", "of the mll4 complex", "and dingwall 2019 .

              dna", "dingwall 2019 .

              dna damage", "2019 .

              dna damage induced", ".

              dna damage induced transcription", "damage induced transcription of", "induced transcription of tp53", "transcription of tp53 target", "of tp53 target genes", "tp53 target genes requires", "target genes requires both", "genes requires both kmt2c", "requires both kmt2c and", "both kmt2c and kmt2d.", "kmt2c and kmt2d. kmt2c", "and kmt2d. kmt2c is", "kmt2d. kmt2c is also", "kmt2c is also implicated", "is also implicated in", "also implicated in tp53", "implicated in tp53 dependent", "in tp53 dependent dna", "tp53 dependent dna double", "dependent dna double strand", "dna double strand break", "double strand break repair", "strand break repair in", "break repair in a", "repair in a transcription", "in a transcription independent", "a transcription independent manner.", "transcription independent manner. ktm2c", "independent manner. ktm2c and", "manner. ktm2c and kmt2d", "ktm2c and kmt2d contribute", "and kmt2d contribute to", "kmt2d contribute to maintenance", "contribute to maintenance of", "to maintenance of epithelial", "maintenance of epithelial cell", "of epithelial cell states", "epithelial cell states by", "cell states by negatively", "states by negatively regulating", "by negatively regulating the", "negatively regulating the epithelial", "regulating the epithelial to", "the epithelial to mesenchymal", "epithelial to mesenchymal transition.", "to mesenchymal transition. kmt2c", "mesenchymal transition. kmt2c mutations", "transition. kmt2c mutations in", "kmt2c mutations in lung", "mutations in lung and", "in lung and breast", "lung and breast cancer", "and breast cancer are", "breast cancer are frequently", "cancer are frequently found", "are frequently found in", "frequently found in the", "found in the first", "in the first phd", "the first phd that", "first phd that is", "phd that is involved", "that is involved in", "is involved in the", "involved in the interaction", "in the interaction with", "the interaction with the", "interaction with the bap1", "with the bap1 histone", "the bap1 histone deubiquitinating", "bap1 histone deubiquitinating complex", "deubiquitinating complex linked", "complex linked to", "linked to polycomb repressor", "to polycomb repressor complex", "polycomb repressor complex dependent", "repressor complex dependent gene", "complex dependent gene silencing", "gene silencing reviewed", "silencing reviewed in", "and dingwall 2019 .

              heterozygous", "dingwall 2019 .

              heterozygous germline", "2019 .

              heterozygous germline lof", ".

              heterozygous germline lof mutations", "germline lof mutations in", "lof mutations in ktm2c", "mutations in ktm2c are", "in ktm2c are associated", "ktm2c are associated with", "are associated with kleefstra", "associated with kleefstra syndrome", "with kleefstra syndrome 2", "kleefstra syndrome 2 and", "syndrome 2 and autism", "2 and autism spectrum", "and autism spectrum disorder", "spectrum disorder reviewed", "disorder reviewed in", "and dingwall 2019 .

              in", "dingwall 2019 .

              in mouse", ".

              in mouse kmt2c", "mouse kmt2c and", "kmt2c and kmt2d are", "and kmt2d are implicated", "kmt2d are implicated in", "are implicated in enhancer", "implicated in enhancer priming", "in enhancer priming and", "enhancer priming and de", "priming and de novo", "and de novo enhancer", "de novo enhancer activation", "novo enhancer activation during", "enhancer activation during embryonic", "activation during embryonic development.", "during embryonic development. this", "embryonic development. this function", "development. this function is", "this function is not", "function is not essential", "is not essential for", "not essential for the", "essential for the maintenance", "for the maintenance of", "the maintenance of cell", "maintenance of cell identity", "of cell identity and", "cell identity and self", "identity and self renewal", "and self renewal of", "self renewal of embryonic", "renewal of embryonic stem", "of embryonic stem cells", "stem cells escs", "escs and somatic", "and somatic cells but", "somatic cells but is", "cells but is necessary", "but is necessary for", "is necessary for esc", "necessary for esc reprogramming", "for esc reprogramming during", "esc reprogramming during differentiation", "reprogramming during differentiation and", "during differentiation and for", "differentiation and for production", "and for production of", "for production of induced", "production of induced pluripotent", "of induced pluripotent stem", "induced pluripotent stem cells", "stem cells ipscs", "ipscs reviewed", "and dingwall 2019 .

              ", "dingwall 2019 .

              knockout", "2019 .

              knockout of", ".

              knockout of kmt2d", "of kmt2d the", "kmt2d the catalytic", "mll4 complex in", "complex in human", "in human colon carcinoma", "human colon carcinoma cell", "colon carcinoma cell line", "carcinoma cell line hct116", "line hct116 which", "hct116 which already", "which already harbors inactivating", "already harbors inactivating mutations", "harbors inactivating mutations in", "inactivating mutations in both", "mutations in both alleles", "in both alleles of", "both alleles of kmt2c", "of kmt2c the", "kmt2c the catalytic", "complex leads", "leads to significant global", "to significant global reduction", "significant global reduction of", "global reduction of h3k4", "reduction of h3k4 monomethylation", "h3k4 monomethylation hu", "monomethylation hu et", "et al. 2013 .", "al. 2013 . knockout", "2013 . knockout studies", ". knockout studies of", "knockout studies of kmt2c", "studies of kmt2c and", "of kmt2c and kmt2d", "kmt2c and kmt2d in", "and kmt2d in hct116", "kmt2d in hct116 cells", "in hct116 cells and", "hct116 cells and mouse", "cells and mouse embryonic", "and mouse embryonic fibroblasts", "embryonic fibroblasts mefs", "mefs implicate at", "implicate at least partially", "at least partially redundant", "least partially redundant roles", "partially redundant roles of", "redundant roles of mll3", "roles of mll3 and", "and mll4 complexes in", "mll4 complexes in h3k4", "complexes in h3k4 monomethylation", "al. 2013 . genome", "2013 . genome wide", ". genome wide chip", "genome wide chip seq", "wide chip seq analysis", "chip seq analysis in", "seq analysis in both", "analysis in both hct116", "in both hct116 cells", "both hct116 cells and", "hct116 cells and mefs", "cells and mefs showed", "and mefs showed that", "mefs showed that ~80%", "showed that ~80% of", "that ~80% of the", "~80% of the mll4", "of the mll4 peaks", "the mll4 peaks are", "mll4 peaks are enriched", "peaks are enriched at", "are enriched at intergenic", "enriched at intergenic and", "at intergenic and intragenic", "intergenic and intragenic regions", "intragenic regions while", "regions while only", "while only ~20% of", "only ~20% of the", "~20% of the peaks", "of the peaks map", "the peaks map to", "peaks map to transcription", "map to transcription start", "to transcription start sites", "start sites tss", "tss hu", "al. 2013 . mll4", "2013 . mll4 binding", ". mll4 binding sites", "mll4 binding sites at", "binding sites at sae1", "sites at sae1 and", "at sae1 and ap3b1", "sae1 and ap3b1 gene", "and ap3b1 gene loci", "ap3b1 gene loci in", "gene loci in hct116", "loci in hct116 cells", "cells and at", "and at nanog and", "at nanog and lefty1", "nanog and lefty1 loci", "and lefty1 loci in", "lefty1 loci in mefs", "in mefs are", "mefs are co", "are co occupied by", "co occupied by enhancer", "occupied by enhancer region", "by enhancer region markers", "enhancer region markers h3k4me1", "markers h3k4me1 ep300", "ep300 and acetylated", "acetylated h3k27 hu", "h3k27 hu et", "al. 2013 . many", "2013 . many of", ". many of the", "many of the genes", "of the genes associated", "the genes associated with", "genes associated with mll3/mll4", "associated with mll3/mll4 bound", "with mll3/mll4 bound enhancers", "mll3/mll4 bound enhancers in", "bound enhancers in hct116", "enhancers in hct116 cells", "in hct116 cells are", "hct116 cells are implicated", "cells are implicated in", "are implicated in intracellular", "implicated in intracellular signaling", "intracellular signaling while", "signaling while genes", "while genes associated with", "associated with mll3/mll4 independent", "with mll3/mll4 independent enhancers", "mll3/mll4 independent enhancers tend", "independent enhancers tend to", "enhancers tend to be", "tend to be implicated", "to be implicated in", "be implicated in regulation", "implicated in regulation of", "in regulation of gene", "gene expression hu", "expression hu et", "et al. 2013 .

              hoxa9", "2013 .

              hoxa9 encoded", ".

              hoxa9 encoded by", "encoded by a target", "by a target gene", "a target gene of", "target gene of kmt2a", "of kmt2a mll1", "mll1 and kmt2b", "and kmt2b mll2", "complexes may function", "may function as a", "function as a pioneer", "as a pioneer factor", "a pioneer factor at", "pioneer factor at de", "factor at de novo", "at de novo enhancers", "de novo enhancers in", "novo enhancers in acute", "enhancers in acute myeloid", "in acute myeloid leukemia", "myeloid leukemia aml", "aml and recruit", "and recruit cebpa and", "recruit cebpa and the", "cebpa and the mll3", "and the mll3 and", "and mll4 complexes to", "mll4 complexes to enhancers", "complexes to enhancers of", "to enhancers of leukemogenesis", "enhancers of leukemogenesis promoting", "of leukemogenesis promoting genes", "promoting genes sun", "genes sun et", "sun et al. 2018", "et al. 2018 .

              kmt2d", "al. 2018 .

              kmt2d is", "2018 .

              kmt2d is frequently", ".

              kmt2d is frequently mutated", "frequently mutated in cancer", "in cancer reviewed", "cancer reviewed in", "reviewed in dhar and", "in dhar and lee", "dhar and lee 2021", "lee 2021 and", "2021 and is", "and is one of", "is one of the", "one of the most", "of the most frequently", "the most frequently mutated", "most frequently mutated genes", "frequently mutated genes in", "mutated genes in non", "genes in non hodgkin", "in non hodgkin lymphoma", "hodgkin lymphoma such", "lymphoma such as", "such as follicular lymphoma", "as follicular lymphoma and", "follicular lymphoma and diffuse", "lymphoma and diffuse large", "and diffuse large b", "diffuse large b cell", "large b cell lymphoma", "cell lymphoma where", "lymphoma where loss", "where loss of function", "of function lof", "lof of kmt2d", "of kmt2d appears to", "kmt2d appears to be", "appears to be an", "to be an early", "be an early event", "an early event that", "early event that cooperates", "event that cooperates with", "that cooperates with the", "cooperates with the over", "with the over expression", "the over expression of", "over expression of the", "expression of the bcl2", "of the bcl2 oncogene.", "the bcl2 oncogene. knockout", "bcl2 oncogene. knockout of", "oncogene. knockout of kmt2d", "knockout of kmt2d in", "of kmt2d in mouse", "kmt2d in mouse b", "in mouse b cell", "mouse b cell progenitors", "b cell progenitors impairs", "cell progenitors impairs their", "progenitors impairs their differentiation", "impairs their differentiation and", "their differentiation and promotes", "differentiation and promotes lymphoma", "and promotes lymphoma development.", "promotes lymphoma development. kmt2d", "lymphoma development. kmt2d lof", "development. kmt2d lof in", "kmt2d lof in lymphoma", "lof in lymphoma is", "in lymphoma is associated", "lymphoma is associated with", "is associated with reduced", "associated with reduced h3k4me1", "with reduced h3k4me1 mark", "reduced h3k4me1 mark at", "h3k4me1 mark at enhancers", "mark at enhancers of", "at enhancers of multiple", "enhancers of multiple tumor", "of multiple tumor suppressor", "multiple tumor suppressor genes", "suppressor genes reviewed", "genes reviewed in", "and dingwall 2019 .

              kmt2d", "dingwall 2019 .

              kmt2d chromatin", "2019 .

              kmt2d chromatin enrichment", ".

              kmt2d chromatin enrichment sites", "chromatin enrichment sites significantly", "enrichment sites significantly overlap", "sites significantly overlap with", "significantly overlap with tp53", "overlap with tp53 binding", "with tp53 binding sites.", "tp53 binding sites. aberrant", "binding sites. aberrant transcription", "sites. aberrant transcription associated", "aberrant transcription associated with", "transcription associated with tp53", "associated with tp53 mutations", "with tp53 mutations in", "tp53 mutations in colon", "mutations in colon carcinoma", "in colon carcinoma is", "colon carcinoma is dependent", "carcinoma is dependent on", "is dependent on kmt2d", "dependent on kmt2d mediated", "on kmt2d mediated h3k4", "kmt2d mediated h3k4 monomethylation.", "mediated h3k4 monomethylation. kmt2d", "h3k4 monomethylation. kmt2d can", "monomethylation. kmt2d can be", "kmt2d can be inactivated", "can be inactivated through", "be inactivated through phosphorylation", "inactivated through phosphorylation by", "through phosphorylation by sgk1", "by sgk1 a", "sgk1 a pi3k", "a pi3k effector kinase", "pi3k effector kinase closely", "effector kinase closely related", "kinase closely related to", "closely related to akt1.", "related to akt1. sgk1", "to akt1. sgk1 is", "akt1. sgk1 is the", "sgk1 is the estrogen", "is the estrogen inducible", "the estrogen inducible kinase", "inducible kinase whose", "kinase whose transcription", "whose transcription is collaboratively", "transcription is collaboratively activated", "is collaboratively activated by", "collaboratively activated by esr1", "activated by esr1 and", "by esr1 and kmt2d.", "esr1 and kmt2d. sgk1", "and kmt2d. sgk1 mediated", "kmt2d. sgk1 mediated phosphorylation", "sgk1 mediated phosphorylation on", "mediated phosphorylation on kmt2d", "phosphorylation on kmt2d on", "on kmt2d on serine", "kmt2d on serine s1331", "on serine s1331 near", "serine s1331 near the", "s1331 near the second", "near the second phd", "the second phd results", "second phd results in", "phd results in downregulation", "results in downregulation of", "in downregulation of h3k4", "downregulation of h3k4 monomethylation", "of h3k4 monomethylation at", "h3k4 monomethylation at esr1", "monomethylation at esr1 target", "at esr1 target genes", "target genes thus", "genes thus constituting", "thus constituting a negative", "constituting a negative feedback", "a negative feedback loop", "feedback loop reviewed", "loop reviewed in", "lof mutations in kmt2d", "mutations in kmt2d are", "in kmt2d are associated", "kmt2d are associated with", "are associated with kabuki", "associated with kabuki syndrome", "with kabuki syndrome 1.", "kabuki syndrome 1. kabuki", "syndrome 1. kabuki syndrome", "1. kabuki syndrome patients", "kabuki syndrome patients have", "syndrome patients have a", "patients have a modestly", "have a modestly increased", "a modestly increased predisposition", "modestly increased predisposition to", "increased predisposition to cancer", "to cancer in", "cancer in particular", "particular lymphoma wilms", "lymphoma wilms tumor", "wilms tumor hepatoblastoma", "hepatoblastoma synovial sarcoma", "synovial sarcoma and neuroblastoma.", "sarcoma and neuroblastoma. mice", "and neuroblastoma. mice with", "neuroblastoma. mice with brain", "mice with brain specific", "with brain specific knockout", "brain specific knockout of", "specific knockout of kmt2d", "of kmt2d mll4", "mll4 develop medulloblastoma", "develop medulloblastoma that shows", "medulloblastoma that shows hyperactivation", "that shows hyperactivation of", "shows hyperactivation of ras", "hyperactivation of ras and", "of ras and notch", "ras and notch signaling", "notch signaling reviewed", "signaling reviewed in", "and dingwall 2019 .

              based", "dingwall 2019 .

              based on", "2019 .

              based on mouse", ".

              based on mouse studies", "mouse studies mll3", "studies mll3 and", "and mll4 complexes play", "mll4 complexes play an", "complexes play an important", "play an important role", "an important role in", "important role in adipogenesis", "role in adipogenesis and", "in adipogenesis and myogenesis.", "adipogenesis and myogenesis. kmt2c", "and myogenesis. kmt2c ko", "myogenesis. kmt2c ko mice", "kmt2c ko mice die", "ko mice die around", "mice die around birth", "die around birth with", "around birth with no", "birth with no obvious", "with no obvious morphological", "no obvious morphological abnormalities", "obvious morphological abnormalities in", "morphological abnormalities in embryonic", "abnormalities in embryonic development", "embryonic development while", "development while kmt2d", "while kmt2d ko mice", "kmt2d ko mice show", "ko mice show early", "mice show early embryonic", "show early embryonic lethality", "early embryonic lethality around", "embryonic lethality around e9.5", "around e9.5 lee", "e9.5 lee et", "lee et al. 2013", "al. 2013 . pups", "2013 . pups with", ". pups with kmt2d", "pups with kmt2d ko", "with kmt2d ko in", "kmt2d ko in precursors", "ko in precursors of", "in precursors of brown", "precursors of brown preadipocytes", "of brown preadipocytes and", "brown preadipocytes and skeletal", "preadipocytes and skeletal myocytes", "and skeletal myocytes are", "skeletal myocytes are obtained", "myocytes are obtained at", "are obtained at the", "obtained at the expected", "at the expected mendelian", "the expected mendelian ratio", "expected mendelian ratio but", "mendelian ratio but display", "ratio but display marked", "but display marked reduction", "display marked reduction in", "marked reduction in back", "reduction in back muscles", "in back muscles and", "back muscles and die", "muscles and die immediately", "and die immediately after", "die immediately after birth", "immediately after birth due", "after birth due to", "birth due to breathing", "due to breathing malfunction", "breathing malfunction also", "malfunction also showing", "also showing a decrease", "showing a decrease in", "a decrease in brown", "decrease in brown adipose", "in brown adipose tissue", "brown adipose tissue mass", "tissue mass lee", "mass lee et", "al. 2013 . in", "2013 . in cultured", ". in cultured mouse", "in cultured mouse brown", "cultured mouse brown preadipocytes", "brown preadipocytes ko", "preadipocytes ko of", "ko of kmt2d leads", "of kmt2d leads to", "kmt2d leads to a", "leads to a moderate", "to a moderate differentiation", "a moderate differentiation defect", "moderate differentiation defect along", "differentiation defect along with", "defect along with a", "along with a transient", "with a transient up", "a transient up regulation", "transient up regulation of", "up regulation of kmt2c", "regulation of kmt2c expression", "kmt2c expression whereas", "expression whereas ko", "whereas ko of kmt2c", "ko of kmt2c has", "of kmt2c has no", "kmt2c has no effect", "has no effect on", "no effect on adipogenesis", "on adipogenesis suggesting", "adipogenesis suggesting a", "suggesting a more prominent", "a more prominent role", "more prominent role of", "prominent role of kmt2d", "role of kmt2d in", "of kmt2d in development", "kmt2d in development and", "in development and a", "development and a partial", "and a partial compensation", "a partial compensation of", "partial compensation of kmt2d", "compensation of kmt2d loss", "of kmt2d loss by", "kmt2d loss by kmt2c", "by kmt2c lee", "kmt2c lee et", "al. 2013 . ko", "2013 . ko of", ". ko of kmt2d", "ko of kmt2d 3t3", "of kmt2d 3t3 l1", "kmt2d 3t3 l1 mouse", "3t3 l1 mouse white", "l1 mouse white preadipocytes", "mouse white preadipocytes inhibits", "white preadipocytes inhibits adipogenesis", "inhibits adipogenesis and", "adipogenesis and kmt2c", "and kmt2c and kmt2d", "and kmt2d are also", "kmt2d are also required", "are also required for", "also required for adipogenesis", "required for adipogenesis in", "for adipogenesis in mouse", "adipogenesis in mouse embryonic", "in mouse embryonic fibroblasts", "embryonic fibroblasts lee", "fibroblasts lee et", "al. 2013 . by", "2013 . by chip", ". by chip seq", "chip seq the", "seq the average", "the average length of", "average length of kmt2d", "length of kmt2d binding", "of kmt2d binding regions", "kmt2d binding regions is", "binding regions is between", "regions is between 350", "is between 350 and", "between 350 and 400", "350 and 400 bp", "400 bp and", "bp and the", "and the binding regions", "the binding regions change", "binding regions change dramatically", "regions change dramatically from", "change dramatically from the", "dramatically from the preadipocytes", "from the preadipocytes stage", "the preadipocytes stage to", "preadipocytes stage to the", "stage to the onset", "to the onset of", "the onset of adipogenesis", "of adipogenesis but", "adipogenesis but are", "but are then kmt2d", "are then kmt2d binding", "then kmt2d binding regions", "kmt2d binding regions were", "binding regions were largely", "regions were largely non", "were largely non overlapping", "largely non overlapping between", "non overlapping between brown", "overlapping between brown adipocytes", "between brown adipocytes and", "brown adipocytes and skeletal", "adipocytes and skeletal myocytes", "skeletal myocytes lee", "myocytes lee et", "kmt2c mll3 complex", "mll3 complex together", "complex together with the", "together with the related kmt2d", "the related kmt2d mll4", "kmt2d mll4 complex", "mll4 complex is", "complex is most similar", "is most similar to drosophila", "most similar to drosophila trr", "to drosophila trr trithorax", "drosophila trr trithorax related", "trithorax related and mediates", "related and mediates hitone", "and mediates hitone h3 lysine", "mediates hitone h3 lysine 4", "h3 lysine 4 h3k4", "h3k4 lysine 5", "lysine 5 in nascent histone", "5 in nascent histone h3", "nascent histone h3 monomethylation", "h3 monomethylation with", "monomethylation with the establishment", "with the establishment of the", "the establishment of the h3k4me1", "establishment of the h3k4me1 epigenetic", "of the h3k4me1 epigenetic marks", "h3k4me1 epigenetic marks at", "epigenetic marks at transcription", "marks at transcription enhancers", "at transcription enhancers throughout the", "transcription enhancers throughout the human", "enhancers throughout the human genome", "the human genome for", "human genome for review", "for review please refer", "review please refer to", "please refer to hu et", "refer to hu et al.", "to hu et al. 2013", "et al. 2013 piunti", "al. 2013 piunti and", "2013 piunti and shilatifard", "and shilatifard 2016 klonou", "shilatifard 2016 klonou et", "2016 klonou et al.", "klonou et al. 2021 .

              the", "et al. 2021 .

              the mll3", "al. 2021 .

              the mll3 and", "2021 .

              the mll3 and mll4", ".

              the mll3 and mll4 complexes", "mll3 and mll4 complexes monomethylate", "and mll4 complexes monomethylate h3k4", "mll4 complexes monomethylate h3k4 at", "complexes monomethylate h3k4 at transcription", "monomethylate h3k4 at transcription enhancers", "h3k4 at transcription enhancers throughout", "the human genome with", "human genome with estimates", "genome with estimates ranging", "with estimates ranging from approximately", "estimates ranging from approximately 12", "ranging from approximately 12 000", "from approximately 12 000 to", "approximately 12 000 to over", "12 000 to over 20", "000 to over 20 000", "to over 20 000 sites", "20 000 sites depending", "000 sites depending on", "sites depending on the", "depending on the cell type", "on the cell type and", "the cell type and developmental", "cell type and developmental stage.", "type and developmental stage. full", "and developmental stage. full activation", "developmental stage. full activation of", "stage. full activation of gene", "full activation of gene expression", "activation of gene expression through", "of gene expression through mll3", "gene expression through mll3 and", "expression through mll3 and mll4", "through mll3 and mll4 complex", "mll3 and mll4 complex target", "and mll4 complex target enhancers", "mll4 complex target enhancers appears", "complex target enhancers appears to", "target enhancers appears to require", "enhancers appears to require simultaneous", "appears to require simultaneous monomethylation", "to require simultaneous monomethylation of", "require simultaneous monomethylation of h3k4", "simultaneous monomethylation of h3k4 by", "monomethylation of h3k4 by mll3", "of h3k4 by mll3 and/or", "h3k4 by mll3 and/or mll4", "by mll3 and/or mll4 complexes", "and/or mll4 complexes and", "mll4 complexes and acetylation", "complexes and acetylation of", "and acetylation of h3k27 by", "acetylation of h3k27 by the", "of h3k27 by the histone", "h3k27 by the histone acetyltransferase", "by the histone acetyltransferase p300/cbp", "histone acetyltransferase p300/cbp recruited", "acetyltransferase p300/cbp recruited to", "p300/cbp recruited to enhancers", "recruited to enhancers through direct", "to enhancers through direct interactions", "enhancers through direct interactions with", "through direct interactions with the", "direct interactions with the mll3", "interactions with the mll3 and", "with the mll3 and mll4", "the mll3 and mll4 complexes.", "mll3 and mll4 complexes. kdm6a", "mll4 complexes. kdm6a also", "complexes. kdm6a also known", "kdm6a also known as", "as utx a", "utx a lysine", "a lysine demethylase that acts", "lysine demethylase that acts as", "demethylase that acts as an", "that acts as an accessory", "acts as an accessory subunit", "as an accessory subunit of", "an accessory subunit of mll3", "accessory subunit of mll3 and", "subunit of mll3 and mll4", "of mll3 and mll4 complexes", "and mll4 complexes facilitates", "mll4 complexes facilitates h3k27", "complexes facilitates h3k27 acetylation", "facilitates h3k27 acetylation by removing", "h3k27 acetylation by removing inhibitory", "acetylation by removing inhibitory methyl", "by removing inhibitory methyl groups", "removing inhibitory methyl groups from", "inhibitory methyl groups from h3k27", "groups from h3k27 deposited", "from h3k27 deposited by", "h3k27 deposited by the", "deposited by the polycomb repressor", "by the polycomb repressor prc2", "the polycomb repressor prc2 complex", "repressor prc2 complex reviewed", "prc2 complex reviewed in", "complex reviewed in fagan", "reviewed in fagan and dingwall", "in fagan and dingwall 2019", "fagan and dingwall 2019 .

              kmt2c", "dingwall 2019 .

              kmt2c also", "2019 .

              kmt2c also known", ".

              kmt2c also known as", "as mll3 the", "mll3 the catalytic", "the catalytic subunit of the", "catalytic subunit of the mll3", "subunit of the mll3 complex", "the mll3 complex contains", "mll3 complex contains two", "complex contains two closely", "contains two closely related plant", "two closely related plant homeodomain", "related plant homeodomain phd", "homeodomain phd zinc", "phd zinc finger clusters", "zinc finger clusters with", "finger clusters with 6", "clusters with 6 7", "with 6 7 zinc fingers", "7 zinc fingers in", "zinc fingers in the", "fingers in the n", "in the n terminal region", "n terminal region and", "terminal region and a", "region and a single", "and a single phd zinc", "a single phd zinc finger", "single phd zinc finger near", "phd zinc finger near the", "zinc finger near the c", "finger near the c terminus", "the c terminus which", "c terminus which are", "terminus which are involved", "which are involved in protein", "are involved in protein protein", "involved in protein protein interactions.", "in protein protein interactions. the", "protein protein interactions. the hmg", "protein interactions. the hmg domain", "interactions. the hmg domain in", "the hmg domain in kmt2c", "hmg domain in kmt2c enables", "domain in kmt2c enables dna", "in kmt2c enables dna binding", "enables dna binding while", "dna binding while the", "binding while the set", "while the set domain provides", "the set domain provides catalytic", "set domain provides catalytic activity.", "domain provides catalytic activity. kmt2c", "provides catalytic activity. kmt2c possesses", "catalytic activity. kmt2c possesses multiple", "activity. kmt2c possesses multiple nuclear", "kmt2c possesses multiple nuclear receptor", "multiple nuclear receptor nr", "receptor nr interaction", "interaction motifs llxxl or", "motifs llxxl or lxxll", "or lxxll which", "lxxll which are", "which are important for recruitment", "are important for recruitment of", "important for recruitment of the", "for recruitment of the mll3", "recruitment of the mll3 complex", "of the mll3 complex to", "the mll3 complex to nr", "mll3 complex to nr regulated", "complex to nr regulated enhancers", "nr regulated enhancers reviewed", "regulated enhancers reviewed in", "enhancers reviewed in fagan", "fagan and dingwall 2019 .

              while", "and dingwall 2019 .

              while h3k4", "dingwall 2019 .

              while h3k4 monomethylation", "2019 .

              while h3k4 monomethylation by", ".

              while h3k4 monomethylation by mll3", "h3k4 monomethylation by mll3 and", "monomethylation by mll3 and mll4", "mll3 and mll4 complexes may", "and mll4 complexes may not", "mll4 complexes may not be", "complexes may not be essential", "may not be essential for", "not be essential for expression", "be essential for expression of", "essential for expression of developmental", "for expression of developmental genes", "of developmental genes it", "developmental genes it is", "genes it is likely", "it is likely important for", "is likely important for fine", "likely important for fine tuning", "important for fine tuning of", "for fine tuning of transcription", "fine tuning of transcription levels", "tuning of transcription levels and", "of transcription levels and timing", "levels and timing both", "and timing both during", "timing both during normal", "both during normal development and", "during normal development and in", "normal development and in cancer.", "development and in cancer. although", "and in cancer. although a", "in cancer. although a broad", "cancer. although a broad dispersion", "although a broad dispersion of", "a broad dispersion of cancer", "broad dispersion of cancer mutations", "dispersion of cancer mutations in", "of cancer mutations in the", "cancer mutations in the coding", "mutations in the coding regions", "in the coding regions of", "the coding regions of the", "coding regions of the kmt2c", "regions of the kmt2c and", "of the kmt2c and kmt2d", "the kmt2c and kmt2d genes", "and kmt2d genes as", "kmt2d genes as well", "genes as well as", "as well as the presence", "well as the presence of", "as the presence of many", "the presence of many truncating", "presence of many truncating mutations", "many truncating mutations imply", "truncating mutations imply a", "mutations imply a tumor", "imply a tumor suppressor role", "tumor suppressor role activating", "suppressor role activating mutations", "role activating mutations in", "activating mutations in the set", "mutations in the set domains", "in the set domains have", "the set domains have also", "set domains have also been", "domains have also been reported", "also been reported suggesting", "been reported suggesting that", "reported suggesting that a", "suggesting that a tumor suppressive", "that a tumor suppressive vs.", "a tumor suppressive vs. oncogenic", "tumor suppressive vs. oncogenic role", "suppressive vs. oncogenic role is", "vs. oncogenic role is context", "oncogenic role is context dependent", "is context dependent reviewed", "context dependent reviewed in", "dependent reviewed in fagan", "and dingwall 2019 .

              kmt2c is", "dingwall 2019 .

              kmt2c is frequently", "2019 .

              kmt2c is frequently mutated", ".

              kmt2c is frequently mutated in", "is frequently mutated in cancer.", "frequently mutated in cancer. kmt2c", "mutated in cancer. kmt2c may", "in cancer. kmt2c may be", "cancer. kmt2c may be important", "kmt2c may be important for", "may be important for driving", "be important for driving hormone", "important for driving hormone stimulated", "for driving hormone stimulated proliferation", "driving hormone stimulated proliferation of", "hormone stimulated proliferation of breast", "stimulated proliferation of breast cancer", "proliferation of breast cancer cells", "of breast cancer cells that", "breast cancer cells that are", "cancer cells that are esr1", "cells that are esr1 positive", "that are esr1 positive and", "are esr1 positive and erbb2", "esr1 positive and erbb2 negative.", "positive and erbb2 negative. in", "and erbb2 negative. in mice", "negative. in mice simultaneous", "in mice simultaneous overexpression", "mice simultaneous overexpression of", "simultaneous overexpression of pik3ca and", "overexpression of pik3ca and inactivation", "of pik3ca and inactivation of", "pik3ca and inactivation of the", "and inactivation of the kmt2c", "inactivation of the kmt2c blocks", "of the kmt2c blocks differentiation", "the kmt2c blocks differentiation of", "kmt2c blocks differentiation of the", "blocks differentiation of the mammary", "differentiation of the mammary gland", "of the mammary gland and", "the mammary gland and leads", "mammary gland and leads to", "gland and leads to increased", "and leads to increased stem", "leads to increased stem cell", "to increased stem cell self", "increased stem cell self renewal", "stem cell self renewal through", "cell self renewal through hif", "self renewal through hif pathway", "renewal through hif pathway activation", "hif pathway activation reviewed", "pathway activation reviewed in", "activation reviewed in fagan", "fagan and dingwall 2019 .

              non", "and dingwall 2019 .

              non small", "dingwall 2019 .

              non small cell", "2019 .

              non small cell lung", ".

              non small cell lung cancer", "cell lung cancer nsclc", "cancer nsclc is", "nsclc is characterized by", "is characterized by frequent co", "characterized by frequent co occurrence", "by frequent co occurrence of", "frequent co occurrence of mutations", "co occurrence of mutations in", "occurrence of mutations in kmt2c", "of mutations in kmt2c and", "mutations in kmt2c and kmt2d", "kmt2c and kmt2d also", "and kmt2d also known", "kmt2d also known as", "known as mll4 the", "as mll4 the catalytic", "mll4 the catalytic subunit", "catalytic subunit of the mll4", "subunit of the mll4 complex", "mll4 complex reviewed", "fagan and dingwall 2019 .

              dna", "and dingwall 2019 .

              dna damage", "dingwall 2019 .

              dna damage induced", "2019 .

              dna damage induced transcription", ".

              dna damage induced transcription of", "damage induced transcription of tp53", "induced transcription of tp53 target", "transcription of tp53 target genes", "of tp53 target genes requires", "tp53 target genes requires both", "target genes requires both kmt2c", "genes requires both kmt2c and", "requires both kmt2c and kmt2d.", "both kmt2c and kmt2d. kmt2c", "kmt2c and kmt2d. kmt2c is", "and kmt2d. kmt2c is also", "kmt2d. kmt2c is also implicated", "kmt2c is also implicated in", "is also implicated in tp53", "also implicated in tp53 dependent", "implicated in tp53 dependent dna", "in tp53 dependent dna double", "tp53 dependent dna double strand", "dependent dna double strand break", "dna double strand break repair", "double strand break repair in", "strand break repair in a", "break repair in a transcription", "repair in a transcription independent", "in a transcription independent manner.", "a transcription independent manner. ktm2c", "transcription independent manner. ktm2c and", "independent manner. ktm2c and kmt2d", "manner. ktm2c and kmt2d contribute", "ktm2c and kmt2d contribute to", "and kmt2d contribute to maintenance", "kmt2d contribute to maintenance of", "contribute to maintenance of epithelial", "to maintenance of epithelial cell", "maintenance of epithelial cell states", "of epithelial cell states by", "epithelial cell states by negatively", "cell states by negatively regulating", "states by negatively regulating the", "by negatively regulating the epithelial", "negatively regulating the epithelial to", "regulating the epithelial to mesenchymal", "the epithelial to mesenchymal transition.", "epithelial to mesenchymal transition. kmt2c", "to mesenchymal transition. kmt2c mutations", "mesenchymal transition. kmt2c mutations in", "transition. kmt2c mutations in lung", "kmt2c mutations in lung and", "mutations in lung and breast", "in lung and breast cancer", "lung and breast cancer are", "and breast cancer are frequently", "breast cancer are frequently found", "cancer are frequently found in", "are frequently found in the", "frequently found in the first", "found in the first phd", "in the first phd that", "the first phd that is", "first phd that is involved", "phd that is involved in", "that is involved in the", "is involved in the interaction", "involved in the interaction with", "in the interaction with the", "the interaction with the bap1", "interaction with the bap1 histone", "with the bap1 histone deubiquitinating", "the bap1 histone deubiquitinating complex", "histone deubiquitinating complex linked", "deubiquitinating complex linked to", "complex linked to polycomb", "linked to polycomb repressor complex", "to polycomb repressor complex dependent", "polycomb repressor complex dependent gene", "repressor complex dependent gene silencing", "dependent gene silencing reviewed", "gene silencing reviewed in", "silencing reviewed in fagan", "fagan and dingwall 2019 .

              heterozygous", "and dingwall 2019 .

              heterozygous germline", "dingwall 2019 .

              heterozygous germline lof", "2019 .

              heterozygous germline lof mutations", ".

              heterozygous germline lof mutations in", "germline lof mutations in ktm2c", "lof mutations in ktm2c are", "mutations in ktm2c are associated", "in ktm2c are associated with", "ktm2c are associated with kleefstra", "are associated with kleefstra syndrome", "associated with kleefstra syndrome 2", "with kleefstra syndrome 2 and", "kleefstra syndrome 2 and autism", "syndrome 2 and autism spectrum", "2 and autism spectrum disorder", "autism spectrum disorder reviewed", "spectrum disorder reviewed in", "disorder reviewed in fagan", "fagan and dingwall 2019 .

              in", "and dingwall 2019 .

              in mouse", "2019 .

              in mouse kmt2c", ".

              in mouse kmt2c and", "mouse kmt2c and kmt2d", "kmt2c and kmt2d are implicated", "and kmt2d are implicated in", "kmt2d are implicated in enhancer", "are implicated in enhancer priming", "implicated in enhancer priming and", "in enhancer priming and de", "enhancer priming and de novo", "priming and de novo enhancer", "and de novo enhancer activation", "de novo enhancer activation during", "novo enhancer activation during embryonic", "enhancer activation during embryonic development.", "activation during embryonic development. this", "during embryonic development. this function", "embryonic development. this function is", "development. this function is not", "this function is not essential", "function is not essential for", "is not essential for the", "not essential for the maintenance", "essential for the maintenance of", "for the maintenance of cell", "the maintenance of cell identity", "maintenance of cell identity and", "of cell identity and self", "cell identity and self renewal", "identity and self renewal of", "and self renewal of embryonic", "self renewal of embryonic stem", "renewal of embryonic stem cells", "embryonic stem cells escs", "cells escs and", "escs and somatic cells", "and somatic cells but is", "somatic cells but is necessary", "cells but is necessary for", "but is necessary for esc", "is necessary for esc reprogramming", "necessary for esc reprogramming during", "for esc reprogramming during differentiation", "esc reprogramming during differentiation and", "reprogramming during differentiation and for", "during differentiation and for production", "differentiation and for production of", "and for production of induced", "for production of induced pluripotent", "production of induced pluripotent stem", "of induced pluripotent stem cells", "pluripotent stem cells ipscs", "ipscs reviewed in", "fagan and dingwall 2019 .

              ", "and dingwall 2019 .

              knockout", "dingwall 2019 .

              knockout of", "2019 .

              knockout of kmt2d", "knockout of kmt2d the", "of kmt2d the catalytic", "kmt2d the catalytic subunit", "the mll4 complex in", "mll4 complex in human", "complex in human colon", "in human colon carcinoma cell", "human colon carcinoma cell line", "colon carcinoma cell line hct116", "cell line hct116 which", "line hct116 which already", "hct116 which already harbors", "which already harbors inactivating mutations", "already harbors inactivating mutations in", "harbors inactivating mutations in both", "inactivating mutations in both alleles", "mutations in both alleles of", "in both alleles of kmt2c", "alleles of kmt2c the", "of kmt2c the catalytic", "kmt2c the catalytic subunit", "mll3 complex leads", "complex leads to", "leads to significant global reduction", "to significant global reduction of", "significant global reduction of h3k4", "global reduction of h3k4 monomethylation", "of h3k4 monomethylation hu", "h3k4 monomethylation hu et", "monomethylation hu et al.", "hu et al. 2013 .", "et al. 2013 . knockout", "al. 2013 . knockout studies", "2013 . knockout studies of", ". knockout studies of kmt2c", "knockout studies of kmt2c and", "studies of kmt2c and kmt2d", "of kmt2c and kmt2d in", "kmt2c and kmt2d in hct116", "and kmt2d in hct116 cells", "kmt2d in hct116 cells and", "in hct116 cells and mouse", "hct116 cells and mouse embryonic", "cells and mouse embryonic fibroblasts", "mouse embryonic fibroblasts mefs", "fibroblasts mefs implicate", "mefs implicate at least", "implicate at least partially redundant", "at least partially redundant roles", "least partially redundant roles of", "partially redundant roles of mll3", "redundant roles of mll3 and", "roles of mll3 and mll4", "mll3 and mll4 complexes in", "and mll4 complexes in h3k4", "mll4 complexes in h3k4 monomethylation", "in h3k4 monomethylation hu", "et al. 2013 . genome", "al. 2013 . genome wide", "2013 . genome wide chip", ". genome wide chip seq", "genome wide chip seq analysis", "wide chip seq analysis in", "chip seq analysis in both", "seq analysis in both hct116", "analysis in both hct116 cells", "in both hct116 cells and", "both hct116 cells and mefs", "hct116 cells and mefs showed", "cells and mefs showed that", "and mefs showed that ~80%", "mefs showed that ~80% of", "showed that ~80% of the", "that ~80% of the mll4", "~80% of the mll4 peaks", "of the mll4 peaks are", "the mll4 peaks are enriched", "mll4 peaks are enriched at", "peaks are enriched at intergenic", "are enriched at intergenic and", "enriched at intergenic and intragenic", "at intergenic and intragenic regions", "and intragenic regions while", "intragenic regions while only", "regions while only ~20%", "while only ~20% of the", "only ~20% of the peaks", "~20% of the peaks map", "of the peaks map to", "the peaks map to transcription", "peaks map to transcription start", "map to transcription start sites", "transcription start sites tss", "tss hu et", "et al. 2013 . mll4", "al. 2013 . mll4 binding", "2013 . mll4 binding sites", ". mll4 binding sites at", "mll4 binding sites at sae1", "binding sites at sae1 and", "sites at sae1 and ap3b1", "at sae1 and ap3b1 gene", "sae1 and ap3b1 gene loci", "and ap3b1 gene loci in", "ap3b1 gene loci in hct116", "gene loci in hct116 cells", "hct116 cells and at", "cells and at nanog", "and at nanog and lefty1", "at nanog and lefty1 loci", "nanog and lefty1 loci in", "and lefty1 loci in mefs", "loci in mefs are", "in mefs are co", "mefs are co occupied", "are co occupied by enhancer", "co occupied by enhancer region", "occupied by enhancer region markers", "by enhancer region markers h3k4me1", "region markers h3k4me1 ep300", "h3k4me1 ep300 and", "ep300 and acetylated h3k27", "and acetylated h3k27 hu", "acetylated h3k27 hu et", "h3k27 hu et al.", "et al. 2013 . many", "al. 2013 . many of", "2013 . many of the", ". many of the genes", "many of the genes associated", "of the genes associated with", "the genes associated with mll3/mll4", "genes associated with mll3/mll4 bound", "associated with mll3/mll4 bound enhancers", "with mll3/mll4 bound enhancers in", "mll3/mll4 bound enhancers in hct116", "bound enhancers in hct116 cells", "enhancers in hct116 cells are", "in hct116 cells are implicated", "hct116 cells are implicated in", "cells are implicated in intracellular", "are implicated in intracellular signaling", "in intracellular signaling while", "intracellular signaling while genes", "signaling while genes associated", "while genes associated with mll3/mll4", "genes associated with mll3/mll4 independent", "associated with mll3/mll4 independent enhancers", "with mll3/mll4 independent enhancers tend", "mll3/mll4 independent enhancers tend to", "independent enhancers tend to be", "enhancers tend to be implicated", "tend to be implicated in", "to be implicated in regulation", "be implicated in regulation of", "implicated in regulation of gene", "in regulation of gene expression", "of gene expression hu", "gene expression hu et", "expression hu et al.", "hu et al. 2013 .

              hoxa9", "al. 2013 .

              hoxa9 encoded", "2013 .

              hoxa9 encoded by", ".

              hoxa9 encoded by a", "encoded by a target gene", "by a target gene of", "a target gene of kmt2a", "gene of kmt2a mll1", "kmt2a mll1 and", "kmt2b mll2 complexes", "mll2 complexes may", "complexes may function as", "may function as a pioneer", "function as a pioneer factor", "as a pioneer factor at", "a pioneer factor at de", "pioneer factor at de novo", "factor at de novo enhancers", "at de novo enhancers in", "de novo enhancers in acute", "novo enhancers in acute myeloid", "enhancers in acute myeloid leukemia", "acute myeloid leukemia aml", "leukemia aml and", "aml and recruit cebpa", "and recruit cebpa and the", "recruit cebpa and the mll3", "cebpa and the mll3 and", "and the mll3 and mll4", "the mll3 and mll4 complexes", "mll3 and mll4 complexes to", "and mll4 complexes to enhancers", "mll4 complexes to enhancers of", "complexes to enhancers of leukemogenesis", "to enhancers of leukemogenesis promoting", "enhancers of leukemogenesis promoting genes", "leukemogenesis promoting genes sun", "promoting genes sun et", "genes sun et al.", "sun et al. 2018 .

              kmt2d", "et al. 2018 .

              kmt2d is", "al. 2018 .

              kmt2d is frequently", "2018 .

              kmt2d is frequently mutated", ".

              kmt2d is frequently mutated in", "is frequently mutated in cancer", "mutated in cancer reviewed", "in cancer reviewed in", "cancer reviewed in dhar", "reviewed in dhar and lee", "in dhar and lee 2021", "and lee 2021 and", "lee 2021 and is", "2021 and is one", "and is one of the", "is one of the most", "one of the most frequently", "of the most frequently mutated", "the most frequently mutated genes", "most frequently mutated genes in", "frequently mutated genes in non", "mutated genes in non hodgkin", "genes in non hodgkin lymphoma", "non hodgkin lymphoma such", "hodgkin lymphoma such as", "lymphoma such as follicular", "such as follicular lymphoma and", "as follicular lymphoma and diffuse", "follicular lymphoma and diffuse large", "lymphoma and diffuse large b", "and diffuse large b cell", "diffuse large b cell lymphoma", "b cell lymphoma where", "cell lymphoma where loss", "lymphoma where loss of", "loss of function lof", "function lof of", "lof of kmt2d appears", "of kmt2d appears to be", "kmt2d appears to be an", "appears to be an early", "to be an early event", "be an early event that", "an early event that cooperates", "early event that cooperates with", "event that cooperates with the", "that cooperates with the over", "cooperates with the over expression", "with the over expression of", "the over expression of the", "over expression of the bcl2", "expression of the bcl2 oncogene.", "of the bcl2 oncogene. knockout", "the bcl2 oncogene. knockout of", "bcl2 oncogene. knockout of kmt2d", "oncogene. knockout of kmt2d in", "knockout of kmt2d in mouse", "of kmt2d in mouse b", "kmt2d in mouse b cell", "in mouse b cell progenitors", "mouse b cell progenitors impairs", "b cell progenitors impairs their", "cell progenitors impairs their differentiation", "progenitors impairs their differentiation and", "impairs their differentiation and promotes", "their differentiation and promotes lymphoma", "differentiation and promotes lymphoma development.", "and promotes lymphoma development. kmt2d", "promotes lymphoma development. kmt2d lof", "lymphoma development. kmt2d lof in", "development. kmt2d lof in lymphoma", "kmt2d lof in lymphoma is", "lof in lymphoma is associated", "in lymphoma is associated with", "lymphoma is associated with reduced", "is associated with reduced h3k4me1", "associated with reduced h3k4me1 mark", "with reduced h3k4me1 mark at", "reduced h3k4me1 mark at enhancers", "h3k4me1 mark at enhancers of", "mark at enhancers of multiple", "at enhancers of multiple tumor", "enhancers of multiple tumor suppressor", "of multiple tumor suppressor genes", "tumor suppressor genes reviewed", "suppressor genes reviewed in", "genes reviewed in fagan", "fagan and dingwall 2019 .

              kmt2d", "and dingwall 2019 .

              kmt2d chromatin", "dingwall 2019 .

              kmt2d chromatin enrichment", "2019 .

              kmt2d chromatin enrichment sites", ".

              kmt2d chromatin enrichment sites significantly", "chromatin enrichment sites significantly overlap", "enrichment sites significantly overlap with", "sites significantly overlap with tp53", "significantly overlap with tp53 binding", "overlap with tp53 binding sites.", "with tp53 binding sites. aberrant", "tp53 binding sites. aberrant transcription", "binding sites. aberrant transcription associated", "sites. aberrant transcription associated with", "aberrant transcription associated with tp53", "transcription associated with tp53 mutations", "associated with tp53 mutations in", "with tp53 mutations in colon", "tp53 mutations in colon carcinoma", "mutations in colon carcinoma is", "in colon carcinoma is dependent", "colon carcinoma is dependent on", "carcinoma is dependent on kmt2d", "is dependent on kmt2d mediated", "dependent on kmt2d mediated h3k4", "on kmt2d mediated h3k4 monomethylation.", "kmt2d mediated h3k4 monomethylation. kmt2d", "mediated h3k4 monomethylation. kmt2d can", "h3k4 monomethylation. kmt2d can be", "monomethylation. kmt2d can be inactivated", "kmt2d can be inactivated through", "can be inactivated through phosphorylation", "be inactivated through phosphorylation by", "inactivated through phosphorylation by sgk1", "phosphorylation by sgk1 a", "by sgk1 a pi3k", "sgk1 a pi3k effector", "a pi3k effector kinase closely", "pi3k effector kinase closely related", "effector kinase closely related to", "kinase closely related to akt1.", "closely related to akt1. sgk1", "related to akt1. sgk1 is", "to akt1. sgk1 is the", "akt1. sgk1 is the estrogen", "sgk1 is the estrogen inducible", "is the estrogen inducible kinase", "estrogen inducible kinase whose", "inducible kinase whose transcription", "kinase whose transcription is", "whose transcription is collaboratively activated", "transcription is collaboratively activated by", "is collaboratively activated by esr1", "collaboratively activated by esr1 and", "activated by esr1 and kmt2d.", "by esr1 and kmt2d. sgk1", "esr1 and kmt2d. sgk1 mediated", "and kmt2d. sgk1 mediated phosphorylation", "kmt2d. sgk1 mediated phosphorylation on", "sgk1 mediated phosphorylation on kmt2d", "mediated phosphorylation on kmt2d on", "phosphorylation on kmt2d on serine", "on kmt2d on serine s1331", "kmt2d on serine s1331 near", "on serine s1331 near the", "serine s1331 near the second", "s1331 near the second phd", "near the second phd results", "the second phd results in", "second phd results in downregulation", "phd results in downregulation of", "results in downregulation of h3k4", "in downregulation of h3k4 monomethylation", "downregulation of h3k4 monomethylation at", "of h3k4 monomethylation at esr1", "h3k4 monomethylation at esr1 target", "monomethylation at esr1 target genes", "esr1 target genes thus", "target genes thus constituting", "genes thus constituting a", "thus constituting a negative feedback", "constituting a negative feedback loop", "negative feedback loop reviewed", "feedback loop reviewed in", "loop reviewed in fagan", "germline lof mutations in kmt2d", "lof mutations in kmt2d are", "mutations in kmt2d are associated", "in kmt2d are associated with", "kmt2d are associated with kabuki", "are associated with kabuki syndrome", "associated with kabuki syndrome 1.", "with kabuki syndrome 1. kabuki", "kabuki syndrome 1. kabuki syndrome", "syndrome 1. kabuki syndrome patients", "1. kabuki syndrome patients have", "kabuki syndrome patients have a", "syndrome patients have a modestly", "patients have a modestly increased", "have a modestly increased predisposition", "a modestly increased predisposition to", "modestly increased predisposition to cancer", "predisposition to cancer in", "to cancer in particular", "cancer in particular lymphoma", "in particular lymphoma wilms", "particular lymphoma wilms tumor", "tumor hepatoblastoma synovial", "hepatoblastoma synovial sarcoma and", "synovial sarcoma and neuroblastoma. mice", "sarcoma and neuroblastoma. mice with", "and neuroblastoma. mice with brain", "neuroblastoma. mice with brain specific", "mice with brain specific knockout", "with brain specific knockout of", "brain specific knockout of kmt2d", "knockout of kmt2d mll4", "kmt2d mll4 develop", "mll4 develop medulloblastoma that", "develop medulloblastoma that shows hyperactivation", "medulloblastoma that shows hyperactivation of", "that shows hyperactivation of ras", "shows hyperactivation of ras and", "hyperactivation of ras and notch", "of ras and notch signaling", "and notch signaling reviewed", "notch signaling reviewed in", "signaling reviewed in fagan", "fagan and dingwall 2019 .

              based", "and dingwall 2019 .

              based on", "dingwall 2019 .

              based on mouse", "2019 .

              based on mouse studies", "on mouse studies mll3", "mouse studies mll3 and", "studies mll3 and mll4", "mll3 and mll4 complexes play", "and mll4 complexes play an", "mll4 complexes play an important", "complexes play an important role", "play an important role in", "an important role in adipogenesis", "important role in adipogenesis and", "role in adipogenesis and myogenesis.", "in adipogenesis and myogenesis. kmt2c", "adipogenesis and myogenesis. kmt2c ko", "and myogenesis. kmt2c ko mice", "myogenesis. kmt2c ko mice die", "kmt2c ko mice die around", "ko mice die around birth", "mice die around birth with", "die around birth with no", "around birth with no obvious", "birth with no obvious morphological", "with no obvious morphological abnormalities", "no obvious morphological abnormalities in", "obvious morphological abnormalities in embryonic", "morphological abnormalities in embryonic development", "in embryonic development while", "embryonic development while kmt2d", "development while kmt2d ko", "while kmt2d ko mice show", "kmt2d ko mice show early", "ko mice show early embryonic", "mice show early embryonic lethality", "show early embryonic lethality around", "early embryonic lethality around e9.5", "lethality around e9.5 lee", "around e9.5 lee et", "e9.5 lee et al.", "lee et al. 2013 .", "et al. 2013 . pups", "al. 2013 . pups with", "2013 . pups with kmt2d", ". pups with kmt2d ko", "pups with kmt2d ko in", "with kmt2d ko in precursors", "kmt2d ko in precursors of", "ko in precursors of brown", "in precursors of brown preadipocytes", "precursors of brown preadipocytes and", "of brown preadipocytes and skeletal", "brown preadipocytes and skeletal myocytes", "preadipocytes and skeletal myocytes are", "and skeletal myocytes are obtained", "skeletal myocytes are obtained at", "myocytes are obtained at the", "are obtained at the expected", "obtained at the expected mendelian", "at the expected mendelian ratio", "the expected mendelian ratio but", "expected mendelian ratio but display", "mendelian ratio but display marked", "ratio but display marked reduction", "but display marked reduction in", "display marked reduction in back", "marked reduction in back muscles", "reduction in back muscles and", "in back muscles and die", "back muscles and die immediately", "muscles and die immediately after", "and die immediately after birth", "die immediately after birth due", "immediately after birth due to", "after birth due to breathing", "birth due to breathing malfunction", "to breathing malfunction also", "breathing malfunction also showing", "malfunction also showing a", "also showing a decrease in", "showing a decrease in brown", "a decrease in brown adipose", "decrease in brown adipose tissue", "in brown adipose tissue mass", "adipose tissue mass lee", "tissue mass lee et", "mass lee et al.", "et al. 2013 . in", "al. 2013 . in cultured", "2013 . in cultured mouse", ". in cultured mouse brown", "in cultured mouse brown preadipocytes", "mouse brown preadipocytes ko", "brown preadipocytes ko of", "preadipocytes ko of kmt2d", "ko of kmt2d leads to", "of kmt2d leads to a", "kmt2d leads to a moderate", "leads to a moderate differentiation", "to a moderate differentiation defect", "a moderate differentiation defect along", "moderate differentiation defect along with", "differentiation defect along with a", "defect along with a transient", "along with a transient up", "with a transient up regulation", "a transient up regulation of", "transient up regulation of kmt2c", "up regulation of kmt2c expression", "of kmt2c expression whereas", "kmt2c expression whereas ko", "expression whereas ko of", "whereas ko of kmt2c has", "ko of kmt2c has no", "of kmt2c has no effect", "kmt2c has no effect on", "has no effect on adipogenesis", "effect on adipogenesis suggesting", "on adipogenesis suggesting a", "adipogenesis suggesting a more", "suggesting a more prominent role", "a more prominent role of", "more prominent role of kmt2d", "prominent role of kmt2d in", "role of kmt2d in development", "of kmt2d in development and", "kmt2d in development and a", "in development and a partial", "development and a partial compensation", "and a partial compensation of", "a partial compensation of kmt2d", "partial compensation of kmt2d loss", "compensation of kmt2d loss by", "of kmt2d loss by kmt2c", "loss by kmt2c lee", "by kmt2c lee et", "kmt2c lee et al.", "et al. 2013 . ko", "al. 2013 . ko of", "2013 . ko of kmt2d", ". ko of kmt2d 3t3", "ko of kmt2d 3t3 l1", "of kmt2d 3t3 l1 mouse", "kmt2d 3t3 l1 mouse white", "3t3 l1 mouse white preadipocytes", "l1 mouse white preadipocytes inhibits", "mouse white preadipocytes inhibits adipogenesis", "preadipocytes inhibits adipogenesis and", "inhibits adipogenesis and kmt2c", "adipogenesis and kmt2c and", "and kmt2c and kmt2d are", "kmt2c and kmt2d are also", "and kmt2d are also required", "kmt2d are also required for", "are also required for adipogenesis", "also required for adipogenesis in", "required for adipogenesis in mouse", "for adipogenesis in mouse embryonic", "adipogenesis in mouse embryonic fibroblasts", "mouse embryonic fibroblasts lee", "embryonic fibroblasts lee et", "fibroblasts lee et al.", "et al. 2013 . by", "al. 2013 . by chip", "2013 . by chip seq", "by chip seq the", "chip seq the average", "seq the average length", "the average length of kmt2d", "average length of kmt2d binding", "length of kmt2d binding regions", "of kmt2d binding regions is", "kmt2d binding regions is between", "binding regions is between 350", "regions is between 350 and", "is between 350 and 400", "between 350 and 400 bp", "and 400 bp and", "400 bp and the", "bp and the binding", "and the binding regions change", "the binding regions change dramatically", "binding regions change dramatically from", "regions change dramatically from the", "change dramatically from the preadipocytes", "dramatically from the preadipocytes stage", "from the preadipocytes stage to", "the preadipocytes stage to the", "preadipocytes stage to the onset", "stage to the onset of", "to the onset of adipogenesis", "onset of adipogenesis but", "of adipogenesis but are", "adipogenesis but are then", "but are then kmt2d binding", "are then kmt2d binding regions", "then kmt2d binding regions were", "kmt2d binding regions were largely", "binding regions were largely non", "regions were largely non overlapping", "were largely non overlapping between", "largely non overlapping between brown", "non overlapping between brown adipocytes", "overlapping between brown adipocytes and", "between brown adipocytes and skeletal", "brown adipocytes and skeletal myocytes", "and skeletal myocytes lee", "skeletal myocytes lee et", "myocytes lee et al." ] }, { "record_id": "GLY_000594_1_2165", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9841922", "r hsa", "hsa 9841922", "r hsa 9841922" ] }, { "record_id": "GLY_000594_1_2165", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mll4 and", "and mll3", "mll3 complexes", "complexes regulate", "regulate expression", "expression of", "of pparg", "pparg target", "target genes", "genes in", "in adipogenesis", "adipogenesis and", "and hepatic", "hepatic steatosis", "mll4 and mll3", "and mll3 complexes", "mll3 complexes regulate", "complexes regulate expression", "regulate expression of", "expression of pparg", "of pparg target", "pparg target genes", "target genes in", "genes in adipogenesis", "in adipogenesis and", "adipogenesis and hepatic", "and hepatic steatosis", "mll4 and mll3 complexes", "and mll3 complexes regulate", "mll3 complexes regulate expression", "complexes regulate expression of", "regulate expression of pparg", "expression of pparg target", "of pparg target genes", "pparg target genes in", "target genes in adipogenesis", "genes in adipogenesis and", "in adipogenesis and hepatic", "adipogenesis and hepatic steatosis", "mll4 and mll3 complexes regulate", "and mll3 complexes regulate expression", "mll3 complexes regulate expression of", "complexes regulate expression of pparg", "regulate expression of pparg target", "expression of pparg target genes", "of pparg target genes in", "pparg target genes in adipogenesis", "target genes in adipogenesis and", "genes in adipogenesis and hepatic", "in adipogenesis and hepatic steatosis", "the ligand", "ligand activated", "activated complex", "complex of", "of a", "a master", "master transcription", "transcription regulator", "regulator of", "of adipogenesis", "nuclear receptor", "receptor pparg", "and its", "its partner", "receptor rxra", "recruits mll3", "mll3 and", "and mll4", "mll4 complexes", "complexes to", "to target", "target gene", "gene loci", "leading to", "to establishment", "establishment of", "of activating", "activating epigenetic", "epigenetic chromatin", "chromatin marks.", "marks. the", "the existing", "existing experimental", "experimental evidence", "evidence implies", "implies that", "that mll3", "mll3 ascom", "ascom and", "mll4 ascom", "ascom complexes", "complexes are", "are recruited", "recruited to", "to pparg:rxra", "pparg:rxra target", "target loci", "as described", "described below.

              pparg", "below.

              pparg isoform", "isoform pparg2", "pparg2 positive", "positive adipocyte", "adipocyte nuclei", "nuclei isolated", "isolated from", "from visceral", "visceral adipose", "adipose tissue", "tissue show", "show significantly", "significantly higher", "higher expression", "expression level", "level of", "of kmt2c", "the catalytic", "catalytic subunit", "subunit of", "of the", "the mll3", "mll3 complex", "and paxip1", "a cofactor", "cofactor of", "of mll3", "and kmt2d", "than pparg2", "pparg2 negative", "negative nuclei", "yu et", "et al.", "al. 2016", "2016 .", ". based", "based on", "on mouse", "mouse studies", "an accessory", "accessory subunit", "is required", "required for", "for adipogenesis", "adipogenesis in", "in mouse", "mouse embryonic", "embryonic fibroblasts", "and primary", "primary preadipocytes.", "preadipocytes. paxip1", "paxip1 deficient", "deficient mefs", "mefs show", "show significant", "significant defects", "defects in", "in both", "both pparg", "and cebpa", "cebpa stimulated", "stimulated adipogenesis", "cho et", "al. 2009", "2009 .", ". knockout", "knockout of", "of paxip1", "paxip1 gene", "gene in", "in brown", "brown adipose", "leads to", "to significant", "significant decrease", "decrease of", "of bat", "bat in", "in knockout", "knockout mice", "and a", "a significant", "of expression", "of markers", "markers shared", "shared between", "between white", "white adipose", "tissue and", "and bat", "such as", "as pparg", "and fabp4", "as well", "well as", "as bat", "bat specific/prevalent", "specific/prevalent markers", "markers prdm16", "cox5b and", "and cox8b", ". paxip1", "paxip1 bat", "bat knockout", "mice are", "are cold", "cold intolerant", "with impaired", "impaired cold", "cold mediated", "mediated induction", "induction of", "of genes", "genes involved", "involved in", "in fatty", "fatty acid", "acid catabolism", "as cpt1a", "and mlycd", "2009 .

              in", ".

              in prostate", "prostate cancer", "kmt2d and", "and pparg", "pparg are", "are overexpressed", "overexpressed at", "at the", "the protein", "protein level", "level relative", "relative to", "to the", "the normal", "normal tissue", "zhai et", "al. 2022", "2022 .", ". kmt2d", "kmt2d knockdown", "knockdown significantly", "significantly reduces", "reduces the", "the lipid", "lipid droplet", "droplet content", "content in", "in prostate", "cancer cell", "cell lines", ". in", "cancer tumors", "kmt2d mrna", "mrna expression", "expression significantly", "significantly correlates", "correlates with", "with mrna", "of lipid", "lipid metabolism", "metabolism genes", "genes fasn", "and acly", "knockdown in", "lines leads", "decrease in", "in the", "the mrna", "mrna levels", "levels of", "of acc", "and fasn", ". stimulation", "stimulation of", "pparg by", "by the", "the synthetic", "synthetic agonist", "agonist rosiglitazone", "rosiglitazone stimulates", "stimulates lipid", "lipid synthesis", "synthesis in", "but the", "the effect", "effect of", "of rosiglitazone", "rosiglitazone is", "is diminished", "diminished upon", "upon kmt2d", "2022 .

              in", ".

              in addition", "addition to", "to regulating", "regulating genes", "in lipid", "the pparg:rxra", "pparg:rxra complex", "nielsen et", "al. 2008", "and mll3/mll4", "mll3/mll4 complexes", "jang et", "al. 2019:", "2019: supplementary", "supplementary information", "may also", "also regulate", "of some", "some of", "the genes", "in glucose", "glucose metabolism", "metabolism and", "and the", "the tricarboxylic", "tricarboxylic acid", "cycle.

              hepatic steatosis", "steatosis represents", "represents the", "the synthesis", "synthesis and", "and accumulation", "accumulation of", "of triglycerides", "triglycerides in", "in hepatocytes", "hepatocytes which", "which can", "if prolonged", "lead to", "the development", "development of", "of non", "non alcoholic", "alcoholic fatty", "fatty liver", "liver disease", "that can", "can progress", "progress to", "to non", "alcoholic steatohepatitis", "ultimately resulting", "resulting in", "in liver", "liver cirrhosis", "hardy et", ". like", "like kmt2c", "delta/delta mice", "which express", "express catalytically", "catalytically inactive", "inactive kmt2c", "saha et", "lee s.", "lee j.", "j. et", "mll4 +/", "with deletion", "deletion of", "of one", "one allele", "allele of", "of kmt2d", "are resistant", "resistant to", "to high", "high fat", "fat diet", "diet induced", "induced hepatic", "with kmt2d+/", "livers accumulating", "accumulating much", "much less", "less fat", "fat relative", "to wild", "wild type", "type littermate", "littermate controls", "controls in", "in response", "response to", "diet feeding", "kim et", ". bulk", "bulk transcriptomic", "transcriptomic analysis", "analysis of", "of kmt2d+/", "mouse livers", "livers shows", "shows that", "that the", "the expression", "a large", "large portion", "portion of", "of high", "diet controlled", "controlled genes", "genes requires", "requires kmt2d", ". among", "among the", "the defined", "defined hepatic", "hepatic steatotic", "steatotic transcription", "transcription factors", "which include", "include mlxipl", "isoform srebp1c", "srebp 1c", "the liver", "liver x", "x receptors", "\u2013 nr1h3", "and nr1h2", "kmt2d has", "has been", "been reported", "reported to", "to associate", "associate with", "with lxrs", "2008 .", ". no", "no association", "association between", "between mouse", "mouse orthologs", "orthologs of", "and mlxipl", "mlxipl or", "or srebp1c", "srebp1c could", "could be", "be detected", "the ligand activated", "ligand activated complex", "activated complex of", "complex of a", "of a master", "a master transcription", "master transcription regulator", "transcription regulator of", "regulator of adipogenesis", "adipogenesis nuclear", "nuclear receptor pparg", "pparg and", "and its partner", "partner nuclear", "nuclear receptor rxra", "rxra recruits", "recruits mll3 and", "mll3 and mll4", "and mll4 complexes", "mll4 complexes to", "complexes to target", "to target gene", "target gene loci", "loci leading", "leading to establishment", "to establishment of", "establishment of activating", "of activating epigenetic", "activating epigenetic chromatin", "epigenetic chromatin marks.", "chromatin marks. the", "marks. the existing", "the existing experimental", "existing experimental evidence", "experimental evidence implies", "evidence implies that", "implies that mll3", "that mll3 ascom", "mll3 ascom and", "ascom and mll4", "and mll4 ascom", "mll4 ascom complexes", "ascom complexes are", "complexes are recruited", "are recruited to", "recruited to pparg:rxra", "to pparg:rxra target", "pparg:rxra target loci", "loci as", "as described below.

              pparg", "described below.

              pparg isoform", "below.

              pparg isoform pparg2", "isoform pparg2 positive", "pparg2 positive adipocyte", "positive adipocyte nuclei", "adipocyte nuclei isolated", "nuclei isolated from", "isolated from visceral", "from visceral adipose", "visceral adipose tissue", "adipose tissue show", "tissue show significantly", "show significantly higher", "significantly higher expression", "higher expression level", "expression level of", "level of kmt2c", "kmt2c the", "the catalytic subunit", "catalytic subunit of", "subunit of the", "of the mll3", "the mll3 complex", "complex and", "paxip1 a", "a cofactor of", "cofactor of mll3", "of mll3 and", "mll3 and kmt2d", "kmt2d mll4", "complexes than", "than pparg2 negative", "pparg2 negative nuclei", "nuclei yu", "yu et al.", "et al. 2016", "al. 2016 .", "2016 . based", ". based on", "based on mouse", "on mouse studies", "studies paxip1", "paxip1 ptip", "an accessory subunit", "accessory subunit of", "subunit of mll3", "complexes is", "is required for", "required for adipogenesis", "for adipogenesis in", "adipogenesis in mouse", "in mouse embryonic", "mouse embryonic fibroblasts", "fibroblasts mefs", "mefs and", "and primary preadipocytes.", "primary preadipocytes. paxip1", "preadipocytes. paxip1 deficient", "paxip1 deficient mefs", "deficient mefs show", "mefs show significant", "show significant defects", "significant defects in", "defects in both", "in both pparg", "and cebpa stimulated", "cebpa stimulated adipogenesis", "adipogenesis cho", "cho et al.", "et al. 2009", "al. 2009 .", "2009 . knockout", ". knockout of", "knockout of paxip1", "of paxip1 gene", "paxip1 gene in", "gene in brown", "in brown adipose", "brown adipose tissue", "tissue bat", "bat leads", "leads to significant", "to significant decrease", "significant decrease of", "decrease of bat", "of bat in", "bat in knockout", "in knockout mice", "mice and", "and a significant", "a significant decrease", "decrease of expression", "of expression of", "expression of markers", "of markers shared", "markers shared between", "shared between white", "between white adipose", "white adipose tissue", "adipose tissue and", "tissue and bat", "bat such", "such as pparg", "pparg cebpa", "cebpa and", "fabp4 as", "as well as", "well as bat", "as bat specific/prevalent", "bat specific/prevalent markers", "specific/prevalent markers prdm16", "prdm16 cidea", "cidea mpzl2", "mpzl2 eva1", "ntrk3 ucp1", "ucp1 ppargc1a", "ppargc1a pgc1a", "cox5b and cox8b", "cox8b cho", "2009 . paxip1", ". paxip1 bat", "paxip1 bat knockout", "bat knockout mice", "knockout mice are", "mice are cold", "are cold intolerant", "intolerant with", "with impaired cold", "impaired cold mediated", "cold mediated induction", "mediated induction of", "induction of genes", "of genes involved", "genes involved in", "involved in fatty", "in fatty acid", "fatty acid catabolism", "catabolism such", "such as cpt1a", "cpt1a lpl", "lpl and", "mlycd mcd", "al. 2009 .

              in", "2009 .

              in prostate", ".

              in prostate cancer", "cancer kmt2d", "kmt2d and pparg", "and pparg are", "pparg are overexpressed", "are overexpressed at", "overexpressed at the", "at the protein", "the protein level", "protein level relative", "level relative to", "relative to the", "to the normal", "the normal tissue", "tissue zhai", "zhai et al.", "et al. 2022", "al. 2022 .", "2022 . kmt2d", ". kmt2d knockdown", "kmt2d knockdown significantly", "knockdown significantly reduces", "significantly reduces the", "reduces the lipid", "the lipid droplet", "lipid droplet content", "droplet content in", "content in prostate", "in prostate cancer", "prostate cancer cell", "cancer cell lines", "lines zhai", "2022 . in", ". in prostate", "prostate cancer tumors", "tumors kmt2d", "kmt2d mrna expression", "mrna expression significantly", "expression significantly correlates", "significantly correlates with", "correlates with mrna", "with mrna expression", "mrna expression of", "expression of lipid", "of lipid metabolism", "lipid metabolism genes", "metabolism genes fasn", "fasn acc", "acc scd", "scd and", "acly zhai", "kmt2d knockdown in", "knockdown in prostate", "cell lines leads", "lines leads to", "significant decrease in", "decrease in the", "in the mrna", "the mrna levels", "mrna levels of", "levels of acc", "acc acly", "acly and", "fasn zhai", "2022 . stimulation", ". stimulation of", "stimulation of pparg", "of pparg by", "pparg by the", "by the synthetic", "the synthetic agonist", "synthetic agonist rosiglitazone", "agonist rosiglitazone stimulates", "rosiglitazone stimulates lipid", "stimulates lipid synthesis", "lipid synthesis in", "synthesis in prostate", "lines but", "but the effect", "the effect of", "effect of rosiglitazone", "of rosiglitazone is", "rosiglitazone is diminished", "is diminished upon", "diminished upon kmt2d", "upon kmt2d knockdown", "knockdown zhai", "al. 2022 .

              in", "2022 .

              in addition", ".

              in addition to", "addition to regulating", "to regulating genes", "regulating genes involved", "involved in lipid", "in lipid metabolism", "metabolism the", "the pparg:rxra complex", "complex nielsen", "nielsen et al.", "et al. 2008", "2008 and", "and mll3/mll4 complexes", "complexes jang", "jang et al.", "et al. 2019:", "al. 2019: supplementary", "2019: supplementary information", "information may", "may also regulate", "also regulate expression", "expression of some", "of some of", "some of the", "of the genes", "the genes involved", "involved in glucose", "in glucose metabolism", "glucose metabolism and", "metabolism and the", "and the tricarboxylic", "the tricarboxylic acid", "acid tca", "tca cycle.

              hepatic", "cycle.

              hepatic steatosis represents", "steatosis represents the", "represents the synthesis", "the synthesis and", "synthesis and accumulation", "and accumulation of", "accumulation of triglycerides", "of triglycerides in", "triglycerides in hepatocytes", "in hepatocytes which", "hepatocytes which can", "can if", "prolonged lead", "lead to the", "to the development", "the development of", "development of non", "of non alcoholic", "non alcoholic fatty", "alcoholic fatty liver", "fatty liver disease", "disease nafld", "nafld that", "that can progress", "can progress to", "progress to non", "to non alcoholic", "non alcoholic steatohepatitis", "steatohepatitis nash", "ultimately resulting in", "resulting in liver", "in liver cirrhosis", "cirrhosis hardy", "hardy et al.", "2016 . like", ". like kmt2c", "kmt2c mll3", "mll3 delta/delta", "mice which", "which express catalytically", "express catalytically inactive", "catalytically inactive kmt2c", "kmt2c lee", "lee saha", "saha et al.", "2008 lee", "s. lee", "lee j. et", "j. et al.", "+/ mice", "mice with", "with deletion of", "deletion of one", "of one allele", "one allele of", "allele of kmt2d", "kmt2d are", "are resistant to", "resistant to high", "to high fat", "high fat diet", "fat diet induced", "diet induced hepatic", "induced hepatic steatosis", "steatosis with", "kmt2d+/ livers", "livers accumulating much", "accumulating much less", "much less fat", "less fat relative", "fat relative to", "relative to wild", "to wild type", "wild type littermate", "type littermate controls", "littermate controls in", "controls in response", "in response to", "response to high", "fat diet feeding", "feeding kim", "kim et al.", "2016 . bulk", ". bulk transcriptomic", "bulk transcriptomic analysis", "transcriptomic analysis of", "analysis of kmt2d+/", "kmt2d+/ mouse", "mouse livers shows", "livers shows that", "shows that the", "that the expression", "the expression of", "expression of a", "of a large", "a large portion", "large portion of", "portion of high", "of high fat", "fat diet controlled", "diet controlled genes", "controlled genes requires", "genes requires kmt2d", "kmt2d kim", "2016 . among", ". among the", "among the defined", "the defined hepatic", "defined hepatic steatotic", "hepatic steatotic transcription", "steatotic transcription factors", "factors which", "which include mlxipl", "mlxipl chrebp", "srebf1 srebp1", "srebp1 isoform", "srebp1c srebp", "the liver x", "liver x receptors", "receptors lxrs", "lxrs \u2013", "nr1h3 lxra", "lxra and", "nr1h2 lxrb", "pparg kmt2d", "kmt2d has been", "has been reported", "been reported to", "reported to associate", "to associate with", "associate with lxrs", "lxrs lee", "pparg lee", "al. 2008 .", "2008 . no", ". no association", "no association between", "association between mouse", "between mouse orthologs", "mouse orthologs of", "orthologs of kmt2d", "of kmt2d and", "kmt2d and mlxipl", "and mlxipl or", "mlxipl or srebp1c", "or srebp1c could", "srebp1c could be", "could be detected", "detected kim", "the ligand activated complex", "ligand activated complex of", "activated complex of a", "complex of a master", "of a master transcription", "a master transcription regulator", "master transcription regulator of", "transcription regulator of adipogenesis", "of adipogenesis nuclear", "adipogenesis nuclear receptor", "receptor pparg and", "pparg and its", "its partner nuclear", "partner nuclear receptor", "receptor rxra recruits", "rxra recruits mll3", "recruits mll3 and mll4", "mll3 and mll4 complexes", "and mll4 complexes to", "mll4 complexes to target", "complexes to target gene", "to target gene loci", "gene loci leading", "loci leading to", "leading to establishment of", "to establishment of activating", "establishment of activating epigenetic", "of activating epigenetic chromatin", "activating epigenetic chromatin marks.", "epigenetic chromatin marks. the", "chromatin marks. the existing", "marks. the existing experimental", "the existing experimental evidence", "existing experimental evidence implies", "experimental evidence implies that", "evidence implies that mll3", "implies that mll3 ascom", "that mll3 ascom and", "mll3 ascom and mll4", "ascom and mll4 ascom", "and mll4 ascom complexes", "mll4 ascom complexes are", "ascom complexes are recruited", "complexes are recruited to", "are recruited to pparg:rxra", "recruited to pparg:rxra target", "to pparg:rxra target loci", "target loci as", "loci as described", "as described below.

              pparg isoform", "described below.

              pparg isoform pparg2", "below.

              pparg isoform pparg2 positive", "isoform pparg2 positive adipocyte", "pparg2 positive adipocyte nuclei", "positive adipocyte nuclei isolated", "adipocyte nuclei isolated from", "nuclei isolated from visceral", "isolated from visceral adipose", "from visceral adipose tissue", "visceral adipose tissue show", "adipose tissue show significantly", "tissue show significantly higher", "show significantly higher expression", "significantly higher expression level", "higher expression level of", "expression level of kmt2c", "of kmt2c the", "kmt2c the catalytic", "the catalytic subunit of", "catalytic subunit of the", "subunit of the mll3", "of the mll3 complex", "mll3 complex and", "complex and paxip1", "and paxip1 a", "paxip1 a cofactor", "a cofactor of mll3", "cofactor of mll3 and", "of mll3 and kmt2d", "and kmt2d mll4", "complexes than pparg2", "than pparg2 negative nuclei", "negative nuclei yu", "nuclei yu et", "yu et al. 2016", "et al. 2016 .", "al. 2016 . based", "2016 . based on", ". based on mouse", "based on mouse studies", "mouse studies paxip1", "ptip an", "an accessory subunit of", "accessory subunit of mll3", "subunit of mll3 and", "of mll3 and mll4", "mll4 complexes is", "complexes is required", "is required for adipogenesis", "required for adipogenesis in", "for adipogenesis in mouse", "adipogenesis in mouse embryonic", "in mouse embryonic fibroblasts", "embryonic fibroblasts mefs", "mefs and primary", "and primary preadipocytes. paxip1", "primary preadipocytes. paxip1 deficient", "preadipocytes. paxip1 deficient mefs", "paxip1 deficient mefs show", "deficient mefs show significant", "mefs show significant defects", "show significant defects in", "significant defects in both", "defects in both pparg", "both pparg and", "pparg and cebpa", "and cebpa stimulated adipogenesis", "stimulated adipogenesis cho", "adipogenesis cho et", "cho et al. 2009", "et al. 2009 .", "al. 2009 . knockout", "2009 . knockout of", ". knockout of paxip1", "knockout of paxip1 gene", "of paxip1 gene in", "paxip1 gene in brown", "gene in brown adipose", "in brown adipose tissue", "adipose tissue bat", "bat leads to", "leads to significant decrease", "to significant decrease of", "significant decrease of bat", "decrease of bat in", "of bat in knockout", "bat in knockout mice", "knockout mice and", "mice and a", "and a significant decrease", "a significant decrease of", "significant decrease of expression", "decrease of expression of", "of expression of markers", "expression of markers shared", "of markers shared between", "markers shared between white", "shared between white adipose", "between white adipose tissue", "white adipose tissue and", "adipose tissue and bat", "and bat such", "bat such as", "as pparg cebpa", "cebpa and fabp4", "and fabp4 as", "fabp4 as well", "as well as bat", "well as bat specific/prevalent", "as bat specific/prevalent markers", "bat specific/prevalent markers prdm16", "markers prdm16 cidea", "eva1 ntrk3", "pgc1a cox5b", "and cox8b cho", "cox8b cho et", "al. 2009 . paxip1", "2009 . paxip1 bat", ". paxip1 bat knockout", "paxip1 bat knockout mice", "bat knockout mice are", "knockout mice are cold", "mice are cold intolerant", "cold intolerant with", "intolerant with impaired", "with impaired cold mediated", "impaired cold mediated induction", "cold mediated induction of", "mediated induction of genes", "induction of genes involved", "of genes involved in", "genes involved in fatty", "involved in fatty acid", "in fatty acid catabolism", "acid catabolism such", "catabolism such as", "as cpt1a lpl", "lpl and mlycd", "and mlycd mcd", "mcd cho", "et al. 2009 .

              in", "al. 2009 .

              in prostate", "2009 .

              in prostate cancer", "prostate cancer kmt2d", "cancer kmt2d and", "kmt2d and pparg are", "and pparg are overexpressed", "pparg are overexpressed at", "are overexpressed at the", "overexpressed at the protein", "at the protein level", "the protein level relative", "protein level relative to", "level relative to the", "relative to the normal", "to the normal tissue", "normal tissue zhai", "tissue zhai et", "zhai et al. 2022", "et al. 2022 .", "al. 2022 . kmt2d", "2022 . kmt2d knockdown", ". kmt2d knockdown significantly", "kmt2d knockdown significantly reduces", "knockdown significantly reduces the", "significantly reduces the lipid", "reduces the lipid droplet", "the lipid droplet content", "lipid droplet content in", "droplet content in prostate", "content in prostate cancer", "in prostate cancer cell", "prostate cancer cell lines", "cell lines zhai", "lines zhai et", "al. 2022 . in", "2022 . in prostate", ". in prostate cancer", "in prostate cancer tumors", "cancer tumors kmt2d", "tumors kmt2d mrna", "kmt2d mrna expression significantly", "mrna expression significantly correlates", "expression significantly correlates with", "significantly correlates with mrna", "correlates with mrna expression", "with mrna expression of", "mrna expression of lipid", "expression of lipid metabolism", "of lipid metabolism genes", "lipid metabolism genes fasn", "genes fasn acc", "scd and acly", "and acly zhai", "acly zhai et", ". kmt2d knockdown in", "kmt2d knockdown in prostate", "knockdown in prostate cancer", "cancer cell lines leads", "cell lines leads to", "lines leads to significant", "to significant decrease in", "significant decrease in the", "decrease in the mrna", "in the mrna levels", "the mrna levels of", "mrna levels of acc", "of acc acly", "acly and fasn", "and fasn zhai", "fasn zhai et", "al. 2022 . stimulation", "2022 . stimulation of", ". stimulation of pparg", "stimulation of pparg by", "of pparg by the", "pparg by the synthetic", "by the synthetic agonist", "the synthetic agonist rosiglitazone", "synthetic agonist rosiglitazone stimulates", "agonist rosiglitazone stimulates lipid", "rosiglitazone stimulates lipid synthesis", "stimulates lipid synthesis in", "lipid synthesis in prostate", "synthesis in prostate cancer", "cell lines but", "lines but the", "but the effect of", "the effect of rosiglitazone", "effect of rosiglitazone is", "of rosiglitazone is diminished", "rosiglitazone is diminished upon", "is diminished upon kmt2d", "diminished upon kmt2d knockdown", "kmt2d knockdown zhai", "knockdown zhai et", "et al. 2022 .

              in", "al. 2022 .

              in addition", "2022 .

              in addition to", ".

              in addition to regulating", "addition to regulating genes", "to regulating genes involved", "regulating genes involved in", "genes involved in lipid", "involved in lipid metabolism", "lipid metabolism the", "metabolism the pparg:rxra", "pparg:rxra complex nielsen", "complex nielsen et", "nielsen et al. 2008", "al. 2008 and", "2008 and mll3/mll4", "mll3/mll4 complexes jang", "complexes jang et", "jang et al. 2019:", "et al. 2019: supplementary", "al. 2019: supplementary information", "supplementary information may", "information may also", "may also regulate expression", "also regulate expression of", "regulate expression of some", "expression of some of", "of some of the", "some of the genes", "of the genes involved", "the genes involved in", "genes involved in glucose", "involved in glucose metabolism", "in glucose metabolism and", "glucose metabolism and the", "metabolism and the tricarboxylic", "and the tricarboxylic acid", "tricarboxylic acid tca", "tca cycle.

              hepatic steatosis", "cycle.

              hepatic steatosis represents the", "steatosis represents the synthesis", "represents the synthesis and", "the synthesis and accumulation", "synthesis and accumulation of", "and accumulation of triglycerides", "accumulation of triglycerides in", "of triglycerides in hepatocytes", "triglycerides in hepatocytes which", "in hepatocytes which can", "which can if", "can if prolonged", "if prolonged lead", "prolonged lead to", "lead to the development", "to the development of", "the development of non", "development of non alcoholic", "of non alcoholic fatty", "non alcoholic fatty liver", "alcoholic fatty liver disease", "liver disease nafld", "nafld that can", "that can progress to", "can progress to non", "progress to non alcoholic", "to non alcoholic steatohepatitis", "alcoholic steatohepatitis nash", "nash ultimately", "ultimately resulting in liver", "resulting in liver cirrhosis", "liver cirrhosis hardy", "cirrhosis hardy et", "hardy et al. 2016", "al. 2016 . like", "2016 . like kmt2c", "like kmt2c mll3", "mll3 delta/delta mice", "delta/delta mice which", "mice which express", "which express catalytically inactive", "express catalytically inactive kmt2c", "inactive kmt2c lee", "lee saha et", "saha et al. 2008", "al. 2008 lee", "2008 lee s.", "lee s. lee", "s. lee j.", "lee j. et al.", "j. et al. 2008", "2008 kmt2d", "kmt2d mll4 +/", "mll4 +/ mice", "mice with deletion", "with deletion of one", "deletion of one allele", "of one allele of", "one allele of kmt2d", "of kmt2d are", "kmt2d are resistant", "are resistant to high", "resistant to high fat", "to high fat diet", "high fat diet induced", "fat diet induced hepatic", "diet induced hepatic steatosis", "hepatic steatosis with", "steatosis with kmt2d+/", "with kmt2d+/ livers", "kmt2d+/ livers accumulating", "livers accumulating much less", "accumulating much less fat", "much less fat relative", "less fat relative to", "fat relative to wild", "relative to wild type", "to wild type littermate", "wild type littermate controls", "type littermate controls in", "littermate controls in response", "controls in response to", "in response to high", "response to high fat", "high fat diet feeding", "diet feeding kim", "feeding kim et", "kim et al. 2016", "al. 2016 . bulk", "2016 . bulk transcriptomic", ". bulk transcriptomic analysis", "bulk transcriptomic analysis of", "transcriptomic analysis of kmt2d+/", "of kmt2d+/ mouse", "kmt2d+/ mouse livers", "mouse livers shows that", "livers shows that the", "shows that the expression", "that the expression of", "the expression of a", "expression of a large", "of a large portion", "a large portion of", "large portion of high", "portion of high fat", "of high fat diet", "high fat diet controlled", "fat diet controlled genes", "diet controlled genes requires", "controlled genes requires kmt2d", "requires kmt2d kim", "kmt2d kim et", "al. 2016 . among", "2016 . among the", ". among the defined", "among the defined hepatic", "the defined hepatic steatotic", "defined hepatic steatotic transcription", "hepatic steatotic transcription factors", "transcription factors which", "factors which include", "include mlxipl chrebp", "chrebp srebf1", "srebp1 isoform srebp1c", "isoform srebp1c srebp", "srebp1c srebp 1c", "1c the", "the liver x receptors", "x receptors lxrs", "lxrs \u2013 nr1h3", "\u2013 nr1h3 lxra", "lxra and nr1h2", "and nr1h2 lxrb", "lxrb and", "and pparg kmt2d", "pparg kmt2d has", "kmt2d has been reported", "has been reported to", "been reported to associate", "reported to associate with", "to associate with lxrs", "with lxrs lee", "lxrs lee s.", "2008 and pparg", "and pparg lee", "et al. 2008 .", "al. 2008 . no", "2008 . no association", ". no association between", "no association between mouse", "association between mouse orthologs", "between mouse orthologs of", "mouse orthologs of kmt2d", "orthologs of kmt2d and", "of kmt2d and mlxipl", "kmt2d and mlxipl or", "and mlxipl or srebp1c", "mlxipl or srebp1c could", "or srebp1c could be", "srebp1c could be detected", "be detected kim", "detected kim et", "the ligand activated complex of", "ligand activated complex of a", "activated complex of a master", "complex of a master transcription", "of a master transcription regulator", "a master transcription regulator of", "master transcription regulator of adipogenesis", "regulator of adipogenesis nuclear", "of adipogenesis nuclear receptor", "adipogenesis nuclear receptor pparg", "nuclear receptor pparg and", "receptor pparg and its", "pparg and its partner", "and its partner nuclear", "its partner nuclear receptor", "partner nuclear receptor rxra", "nuclear receptor rxra recruits", "receptor rxra recruits mll3", "rxra recruits mll3 and", "recruits mll3 and mll4 complexes", "mll3 and mll4 complexes to", "and mll4 complexes to target", "mll4 complexes to target gene", "complexes to target gene loci", "target gene loci leading", "gene loci leading to", "loci leading to establishment", "leading to establishment of activating", "to establishment of activating epigenetic", "establishment of activating epigenetic chromatin", "of activating epigenetic chromatin marks.", "activating epigenetic chromatin marks. the", "epigenetic chromatin marks. the existing", "chromatin marks. the existing experimental", "marks. the existing experimental evidence", "the existing experimental evidence implies", "existing experimental evidence implies that", "experimental evidence implies that mll3", "evidence implies that mll3 ascom", "implies that mll3 ascom and", "that mll3 ascom and mll4", "mll3 ascom and mll4 ascom", "ascom and mll4 ascom complexes", "and mll4 ascom complexes are", "mll4 ascom complexes are recruited", "ascom complexes are recruited to", "complexes are recruited to pparg:rxra", "are recruited to pparg:rxra target", "recruited to pparg:rxra target loci", "pparg:rxra target loci as", "target loci as described", "loci as described below.

              pparg", "as described below.

              pparg isoform pparg2", "described below.

              pparg isoform pparg2 positive", "below.

              pparg isoform pparg2 positive adipocyte", "isoform pparg2 positive adipocyte nuclei", "pparg2 positive adipocyte nuclei isolated", "positive adipocyte nuclei isolated from", "adipocyte nuclei isolated from visceral", "nuclei isolated from visceral adipose", "isolated from visceral adipose tissue", "from visceral adipose tissue show", "visceral adipose tissue show significantly", "adipose tissue show significantly higher", "tissue show significantly higher expression", "show significantly higher expression level", "significantly higher expression level of", "higher expression level of kmt2c", "level of kmt2c the", "of kmt2c the catalytic", "kmt2c the catalytic subunit", "the catalytic subunit of the", "catalytic subunit of the mll3", "subunit of the mll3 complex", "the mll3 complex and", "mll3 complex and paxip1", "and paxip1 a cofactor", "paxip1 a cofactor of", "a cofactor of mll3 and", "cofactor of mll3 and kmt2d", "mll3 and kmt2d mll4", "kmt2d mll4 complexes", "mll4 complexes than", "complexes than pparg2 negative", "pparg2 negative nuclei yu", "negative nuclei yu et", "nuclei yu et al.", "yu et al. 2016 .", "et al. 2016 . based", "al. 2016 . based on", "2016 . based on mouse", ". based on mouse studies", "on mouse studies paxip1", "studies paxip1 ptip", "ptip an accessory", "an accessory subunit of mll3", "accessory subunit of mll3 and", "subunit of mll3 and mll4", "of mll3 and mll4 complexes", "and mll4 complexes is", "mll4 complexes is required", "complexes is required for", "is required for adipogenesis in", "required for adipogenesis in mouse", "for adipogenesis in mouse embryonic", "adipogenesis in mouse embryonic fibroblasts", "mouse embryonic fibroblasts mefs", "fibroblasts mefs and", "mefs and primary preadipocytes.", "and primary preadipocytes. paxip1 deficient", "primary preadipocytes. paxip1 deficient mefs", "preadipocytes. paxip1 deficient mefs show", "paxip1 deficient mefs show significant", "deficient mefs show significant defects", "mefs show significant defects in", "show significant defects in both", "significant defects in both pparg", "in both pparg and", "both pparg and cebpa", "pparg and cebpa stimulated", "cebpa stimulated adipogenesis cho", "stimulated adipogenesis cho et", "adipogenesis cho et al.", "cho et al. 2009 .", "et al. 2009 . knockout", "al. 2009 . knockout of", "2009 . knockout of paxip1", ". knockout of paxip1 gene", "knockout of paxip1 gene in", "of paxip1 gene in brown", "paxip1 gene in brown adipose", "gene in brown adipose tissue", "brown adipose tissue bat", "tissue bat leads", "bat leads to significant", "leads to significant decrease of", "to significant decrease of bat", "significant decrease of bat in", "decrease of bat in knockout", "of bat in knockout mice", "in knockout mice and", "knockout mice and a", "mice and a significant", "and a significant decrease of", "a significant decrease of expression", "significant decrease of expression of", "decrease of expression of markers", "of expression of markers shared", "expression of markers shared between", "of markers shared between white", "markers shared between white adipose", "shared between white adipose tissue", "between white adipose tissue and", "white adipose tissue and bat", "tissue and bat such", "and bat such as", "bat such as pparg", "such as pparg cebpa", "pparg cebpa and", "and fabp4 as well", "fabp4 as well as", "as well as bat specific/prevalent", "well as bat specific/prevalent markers", "as bat specific/prevalent markers prdm16", "specific/prevalent markers prdm16 cidea", "prdm16 cidea mpzl2", "cidea mpzl2 eva1", "ntrk3 ucp1 ppargc1a", "ucp1 ppargc1a pgc1a", "pgc1a cox5b and", "cox5b and cox8b cho", "and cox8b cho et", "cox8b cho et al.", "et al. 2009 . paxip1", "al. 2009 . paxip1 bat", "2009 . paxip1 bat knockout", ". paxip1 bat knockout mice", "paxip1 bat knockout mice are", "bat knockout mice are cold", "knockout mice are cold intolerant", "are cold intolerant with", "cold intolerant with impaired", "intolerant with impaired cold", "with impaired cold mediated induction", "impaired cold mediated induction of", "cold mediated induction of genes", "mediated induction of genes involved", "induction of genes involved in", "of genes involved in fatty", "genes involved in fatty acid", "involved in fatty acid catabolism", "fatty acid catabolism such", "acid catabolism such as", "catabolism such as cpt1a", "such as cpt1a lpl", "cpt1a lpl and", "mcd cho et", "cho et al. 2009 .

              in", "et al. 2009 .

              in prostate", "al. 2009 .

              in prostate cancer", ".

              in prostate cancer kmt2d", "prostate cancer kmt2d and", "cancer kmt2d and pparg", "kmt2d and pparg are overexpressed", "and pparg are overexpressed at", "pparg are overexpressed at the", "are overexpressed at the protein", "overexpressed at the protein level", "at the protein level relative", "the protein level relative to", "protein level relative to the", "level relative to the normal", "relative to the normal tissue", "the normal tissue zhai", "normal tissue zhai et", "tissue zhai et al.", "zhai et al. 2022 .", "et al. 2022 . kmt2d", "al. 2022 . kmt2d knockdown", "2022 . kmt2d knockdown significantly", ". kmt2d knockdown significantly reduces", "kmt2d knockdown significantly reduces the", "knockdown significantly reduces the lipid", "significantly reduces the lipid droplet", "reduces the lipid droplet content", "the lipid droplet content in", "lipid droplet content in prostate", "droplet content in prostate cancer", "content in prostate cancer cell", "in prostate cancer cell lines", "cancer cell lines zhai", "cell lines zhai et", "lines zhai et al.", "et al. 2022 . in", "al. 2022 . in prostate", "2022 . in prostate cancer", ". in prostate cancer tumors", "prostate cancer tumors kmt2d", "cancer tumors kmt2d mrna", "tumors kmt2d mrna expression", "kmt2d mrna expression significantly correlates", "mrna expression significantly correlates with", "expression significantly correlates with mrna", "significantly correlates with mrna expression", "correlates with mrna expression of", "with mrna expression of lipid", "mrna expression of lipid metabolism", "expression of lipid metabolism genes", "of lipid metabolism genes fasn", "metabolism genes fasn acc", "fasn acc scd", "acc scd and", "and acly zhai et", "acly zhai et al.", "2022 . kmt2d knockdown in", ". kmt2d knockdown in prostate", "kmt2d knockdown in prostate cancer", "knockdown in prostate cancer cell", "prostate cancer cell lines leads", "cancer cell lines leads to", "cell lines leads to significant", "lines leads to significant decrease", "leads to significant decrease in", "to significant decrease in the", "significant decrease in the mrna", "decrease in the mrna levels", "in the mrna levels of", "the mrna levels of acc", "levels of acc acly", "acc acly and", "and fasn zhai et", "fasn zhai et al.", "et al. 2022 . stimulation", "al. 2022 . stimulation of", "2022 . stimulation of pparg", ". stimulation of pparg by", "stimulation of pparg by the", "of pparg by the synthetic", "pparg by the synthetic agonist", "by the synthetic agonist rosiglitazone", "the synthetic agonist rosiglitazone stimulates", "synthetic agonist rosiglitazone stimulates lipid", "agonist rosiglitazone stimulates lipid synthesis", "rosiglitazone stimulates lipid synthesis in", "stimulates lipid synthesis in prostate", "lipid synthesis in prostate cancer", "synthesis in prostate cancer cell", "cancer cell lines but", "cell lines but the", "lines but the effect", "but the effect of rosiglitazone", "the effect of rosiglitazone is", "effect of rosiglitazone is diminished", "of rosiglitazone is diminished upon", "rosiglitazone is diminished upon kmt2d", "is diminished upon kmt2d knockdown", "upon kmt2d knockdown zhai", "kmt2d knockdown zhai et", "knockdown zhai et al.", "zhai et al. 2022 .

              in", "et al. 2022 .

              in addition", "al. 2022 .

              in addition to", "2022 .

              in addition to regulating", ".

              in addition to regulating genes", "addition to regulating genes involved", "to regulating genes involved in", "regulating genes involved in lipid", "genes involved in lipid metabolism", "in lipid metabolism the", "lipid metabolism the pparg:rxra", "metabolism the pparg:rxra complex", "the pparg:rxra complex nielsen", "pparg:rxra complex nielsen et", "complex nielsen et al.", "et al. 2008 and", "al. 2008 and mll3/mll4", "2008 and mll3/mll4 complexes", "and mll3/mll4 complexes jang", "mll3/mll4 complexes jang et", "complexes jang et al.", "jang et al. 2019: supplementary", "et al. 2019: supplementary information", "2019: supplementary information may", "supplementary information may also", "information may also regulate", "may also regulate expression of", "also regulate expression of some", "regulate expression of some of", "expression of some of the", "of some of the genes", "some of the genes involved", "of the genes involved in", "the genes involved in glucose", "genes involved in glucose metabolism", "involved in glucose metabolism and", "in glucose metabolism and the", "glucose metabolism and the tricarboxylic", "metabolism and the tricarboxylic acid", "the tricarboxylic acid tca", "acid tca cycle.

              hepatic", "tca cycle.

              hepatic steatosis represents", "cycle.

              hepatic steatosis represents the synthesis", "steatosis represents the synthesis and", "represents the synthesis and accumulation", "the synthesis and accumulation of", "synthesis and accumulation of triglycerides", "and accumulation of triglycerides in", "accumulation of triglycerides in hepatocytes", "of triglycerides in hepatocytes which", "triglycerides in hepatocytes which can", "hepatocytes which can if", "which can if prolonged", "if prolonged lead to", "prolonged lead to the", "lead to the development of", "to the development of non", "the development of non alcoholic", "development of non alcoholic fatty", "of non alcoholic fatty liver", "non alcoholic fatty liver disease", "fatty liver disease nafld", "disease nafld that", "nafld that can progress", "that can progress to non", "can progress to non alcoholic", "progress to non alcoholic steatohepatitis", "non alcoholic steatohepatitis nash", "nash ultimately resulting", "ultimately resulting in liver cirrhosis", "in liver cirrhosis hardy", "liver cirrhosis hardy et", "cirrhosis hardy et al.", "hardy et al. 2016 .", "et al. 2016 . like", "al. 2016 . like kmt2c", ". like kmt2c mll3", "kmt2c mll3 delta/delta", "delta/delta mice which express", "mice which express catalytically", "which express catalytically inactive kmt2c", "catalytically inactive kmt2c lee", "kmt2c lee saha", "lee saha et al.", "et al. 2008 lee", "al. 2008 lee s.", "lee s. lee j.", "s. lee j. et", "lee j. et al. 2008", "al. 2008 kmt2d", "+/ mice with", "mice with deletion of", "with deletion of one allele", "deletion of one allele of", "of one allele of kmt2d", "allele of kmt2d are", "of kmt2d are resistant", "kmt2d are resistant to", "are resistant to high fat", "resistant to high fat diet", "to high fat diet induced", "high fat diet induced hepatic", "fat diet induced hepatic steatosis", "induced hepatic steatosis with", "hepatic steatosis with kmt2d+/", "with kmt2d+/ livers accumulating", "kmt2d+/ livers accumulating much", "livers accumulating much less fat", "accumulating much less fat relative", "much less fat relative to", "less fat relative to wild", "fat relative to wild type", "relative to wild type littermate", "to wild type littermate controls", "wild type littermate controls in", "type littermate controls in response", "littermate controls in response to", "controls in response to high", "in response to high fat", "response to high fat diet", "to high fat diet feeding", "fat diet feeding kim", "diet feeding kim et", "feeding kim et al.", "kim et al. 2016 .", "et al. 2016 . bulk", "al. 2016 . bulk transcriptomic", "2016 . bulk transcriptomic analysis", ". bulk transcriptomic analysis of", "bulk transcriptomic analysis of kmt2d+/", "analysis of kmt2d+/ mouse", "of kmt2d+/ mouse livers", "kmt2d+/ mouse livers shows", "mouse livers shows that the", "livers shows that the expression", "shows that the expression of", "that the expression of a", "the expression of a large", "expression of a large portion", "of a large portion of", "a large portion of high", "large portion of high fat", "portion of high fat diet", "of high fat diet controlled", "high fat diet controlled genes", "fat diet controlled genes requires", "diet controlled genes requires kmt2d", "genes requires kmt2d kim", "requires kmt2d kim et", "kmt2d kim et al.", "et al. 2016 . among", "al. 2016 . among the", "2016 . among the defined", ". among the defined hepatic", "among the defined hepatic steatotic", "the defined hepatic steatotic transcription", "defined hepatic steatotic transcription factors", "steatotic transcription factors which", "transcription factors which include", "factors which include mlxipl", "which include mlxipl chrebp", "srebf1 srebp1 isoform", "isoform srebp1c srebp 1c", "srebp 1c the", "1c the liver", "liver x receptors lxrs", "receptors lxrs \u2013", "nr1h3 lxra and", "lxrb and pparg", "and pparg kmt2d has", "pparg kmt2d has been", "kmt2d has been reported to", "has been reported to associate", "been reported to associate with", "reported to associate with lxrs", "associate with lxrs lee", "with lxrs lee s.", "al. 2008 and pparg", "pparg lee saha", "saha et al. 2008 .", "et al. 2008 . no", "al. 2008 . no association", "2008 . no association between", ". no association between mouse", "no association between mouse orthologs", "association between mouse orthologs of", "between mouse orthologs of kmt2d", "mouse orthologs of kmt2d and", "orthologs of kmt2d and mlxipl", "of kmt2d and mlxipl or", "kmt2d and mlxipl or srebp1c", "and mlxipl or srebp1c could", "mlxipl or srebp1c could be", "or srebp1c could be detected", "could be detected kim", "be detected kim et", "detected kim et al." ] }, { "record_id": "GLY_000594_1_2166", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9856530", "r hsa", "hsa 9856530", "r hsa 9856530" ] }, { "record_id": "GLY_000594_1_2166", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "high laminar", "laminar flow", "flow shear", "shear stress", "stress activates", "activates signaling", "signaling by", "by piezo1", "piezo1 and", "and pecam1:cdh5:kdr", "pecam1:cdh5:kdr in", "in endothelial", "endothelial cells", "high laminar flow", "laminar flow shear", "flow shear stress", "shear stress activates", "stress activates signaling", "activates signaling by", "signaling by piezo1", "by piezo1 and", "piezo1 and pecam1:cdh5:kdr", "and pecam1:cdh5:kdr in", "pecam1:cdh5:kdr in endothelial", "in endothelial cells", "high laminar flow shear", "laminar flow shear stress", "flow shear stress activates", "shear stress activates signaling", "stress activates signaling by", "activates signaling by piezo1", "signaling by piezo1 and", "by piezo1 and pecam1:cdh5:kdr", "piezo1 and pecam1:cdh5:kdr in", "and pecam1:cdh5:kdr in endothelial", "pecam1:cdh5:kdr in endothelial cells", "high laminar flow shear stress", "laminar flow shear stress 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produced", "by endothelial", "cells modulates", "modulates soluble", "soluble guanylyl", "guanylyl cyclase", "cyclase and", "and cgmp", "cgmp dependent", "dependent kinase", "kinase in", "in surrounding", "surrounding smooth", "smooth muscle", "muscle cells", "to cause", "cause vasodilation", "in feletou", "feletou et", "al. 2008", "2012 .", ". by", "by optimizing", "optimizing blood", "blood flow", "flow without", "without inflammation", "the response", "response to", "to laminar", "stress is", "is atheroprotective.
              laminar", "atheroprotective.
              laminar shear", "stress on", "on endothelial", "cells is", "is detected", "detected by", "by the", "the glycocalyx", "the mechanosensitive", "mechanosensitive ion", "ion channel", "channel piezo1", "piezo1 located", "located on", "on the", "the apex", "apex of", "the cell", "and the", "the pecam1:cdh5:kdr", "pecam1:ve cadherin:vegfr2", "complex located", "the lateral", "lateral surfaces", "surfaces between", "between adjacent", "adjacent cells", "in tanaka", "tanaka et", "al. 2021", "2021 .", ". the", "the active", "active molecular", "molecular components", "mechanisms of", "of activation", "and downstream", "downstream events", "events related", "related to", "to the", "and cilia", "cilia are", "are incompletely", "incompletely characterized", "characterized so", "so the", "the annotation", "annotation here", "here focuses", "focuses more", "more on", "on piezo1", "pecam1:cdh5:kdr complex.
              the", "complex.
              the force", "force of", "flow on", "the membrane", "membrane of", "the endothelial", "endothelial cell", "cell activates", "activates the", "the ion", "channel trpv4", "trpv4 to", "to transport", "transport cations", "notably calcium", "from the", "the extracellular", "extracellular region", "region to", "the cytosol", "in li", "li et", "al. 2014", "ranade et", "fang et", "xiao et", ". cytosolic", "cytosolic calcium", "calcium activates", "the protease", "protease complex", "complex calpain2", "calpain2 to", "to cleave", "cleave the", "the cytoskeletal", "cytoskeletal proteins", "proteins talin1", "talin1 and", "and vinculin", "resulting in", "in changes", "changes to", "the cytoskeleton", "cytoskeleton that", "that alter", "alter the", "the shape", "shape of", "miyazaki et", "al. 2007", "2007 .
              flow", ".
              flow sensitive", "sensitive potassium", "potassium channels", "which may", "may include", "include kir2.1", "kir2.1 and", "and trek1", "and chloride", "chloride channels", "include lrrc8a", "are also", "also observed", "observed to", "to open", "however their", "their mechanisms", "activation and", "events are", "2021 .
              cytosolic", ".
              cytosolic calcium", "activates pannexin", "pannexin channels", "channels to", "to release", "release atp", "wang et", "al. 2016", "which binds", "binds the", "the p2ry2", "receptor on", "cell surface", "surface in", "in an", "an autocrine", "autocrine and", "and paracrine", "paracrine manner", "manner and", "and thereby", "thereby activates", "activates galpha", "galpha q/11", "pi3k akt1", "akt1 signaling.", "signaling. both", "both signaling", "by p2ry2", "p2ry2 and", "and signaling", "by a", "a mechanosensitive", "mechanosensitive complex", "complex containing", "containing pecam1", "pecam1 and", "and kdr", "inferred from", "from mouse", "mouse homologs", "homologs in", "in tzima", "tzima et", "al. 2005", "produce phosphatidylinositol", "phosphatidylinositol 3", "3 4", "4 5", "5 trisphosphate", "binds akt1", "akt1 and", "and enhances", "enhances the", "the phosphorylation", "phosphorylation of", "of akt1", "akt1 on", "on serine", "serine 475", "475 by", "the mtorc2", "mtorc2 complex.
              through", "complex.
              through a", "a pi3k", "pi3k independent", "independent mechanism", "p2ry2 signaling", "signaling and", "and cytosolic", "calcium activate", "activate the", "the kinase", "kinase pdpk1", "which phosphorylates", "phosphorylates the", "kinase pkn2", "jin et", ". phospho", "phospho pkn2", "pkn2 then", "then phosphorylates", "phosphorylates akt1", "on threonine", "threonine 308", "phospho t308", "t308 s475", "s475 akt1", "akt1 phosphorylates", "phosphorylates serine", "serine 1177", "1177 of", "of nos3", "while phospho", "pkn2 also", "also phosphorylates", "serine 1179", "1179 of", "causing increased", "increased nitric", "oxide production", "in cabou", "cabou and", "and martinez", "martinez 2022", "2022 .
              laminar", ".
              laminar shear", "stress increases", "increases secretion", "secretion of", "of adrenomedullin", "a vasodilator", "cells through", "through an", "an uncharacterized", "uncharacterized mechanism", "iring et", "al. 2019", "2019 .", ". adm", "adm binds", "the am1", "am1 receptor", "receptor and", "and signals", "signals through", "through g", "g alpha", "alpha s", "adenylate cyclase", "and resultant", "resultant camp", "camp to", "to activate", "activate protein", "protein kinase", "kinase a", "to phosphorylate", "phosphorylate serine", "serine 633", "633 of", "further increasing", "increasing nitric", "2019 .
              the", ".
              the sphingosine", "sphingosine 1", "1 phosphate", "phosphate receptor", "receptor s1pr1", "which couples", "couples to", "to galpha", "galpha i1", "and galpha", "galpha i3", "contributes in", "in a", "a ligand", "ligand independent", "independent manner", "manner to", "to activation", "activation of", "of akt", "akt and", "and nos3", "however the", "the intermediate", "intermediate steps", "steps are", ". other", "other gpcrs", "gpcrs such", "such as", "as gpr68", "gpr68 also", "also become", "become activated", "possibly through", "through flow", "flow induced", "induced deformation", "deformation of", "extracellular domain", "laminar shear stress", "shear stress produced", "stress produced by", "produced by high", "by high fluid", "high fluid flow", "fluid flow across", "flow across endothelial", "across endothelial cells", "endothelial cells causes", "cells causes the", "causes the cells", "the cells to", "cells to produce", "to produce vasodilatory", "produce vasodilatory nitric", "vasodilatory nitric oxide", "oxide no", "no and", "and to elongate", "to elongate from", "elongate from polygonal", "from polygonal to", "polygonal to ellipsoid", "to ellipsoid such", "ellipsoid such that", "such that their", "that their long", "their long axes", "long axes become", "axes become parallel", "become parallel with", "parallel with direction", "with direction of", "direction of the", "of the flow", "flow nerem", "nerem et al.", "et al. 1981", "1981 dewey", "dewey et al.", "1981 reviewed", "reviewed in tamargo", "in tamargo et", "tamargo et al.", "et al. 2023", "al. 2023 .", "2023 . nitric", ". nitric oxide", "nitric oxide produced", "oxide produced by", "produced by endothelial", "by endothelial cells", "endothelial cells modulates", "cells modulates soluble", "modulates soluble guanylyl", "soluble guanylyl cyclase", "guanylyl cyclase and", "cyclase and cgmp", "and cgmp dependent", "cgmp dependent kinase", "dependent kinase in", "kinase in surrounding", "in surrounding smooth", "surrounding smooth muscle", "smooth muscle cells", "muscle cells to", "cells to cause", "to cause vasodilation", "vasodilation reviewed", "reviewed in feletou", "in feletou et", "feletou et al.", "et al. 2008", "2008 2012", "2012 . by", ". by optimizing", "by optimizing blood", "optimizing blood flow", "blood flow without", "flow without inflammation", "inflammation the", "the response to", "response to laminar", "to laminar shear", "shear stress is", "stress is atheroprotective.
              laminar", "is atheroprotective.
              laminar shear", "atheroprotective.
              laminar shear stress", "shear stress on", "stress on endothelial", "on endothelial cells", "endothelial cells is", "cells is detected", "is detected by", "detected by the", "by the glycocalyx", "glycocalyx caveolae", "caveolae cilia", "cilia the", "the mechanosensitive ion", "mechanosensitive ion channel", "ion channel piezo1", "channel piezo1 located", "piezo1 located on", "located on the", "on the apex", "the apex of", "apex of the", "of the cell", "cell and", "and the pecam1:cdh5:kdr", "pecam1:cdh5:kdr pecam1:ve", "cadherin:vegfr2 complex", "complex located on", "on the lateral", "the lateral surfaces", "lateral surfaces between", "surfaces between adjacent", "between adjacent cells", "cells reviewed", "reviewed in tanaka", "in tanaka et", "tanaka et al.", "et al. 2021", "al. 2021 .", "2021 . the", ". the active", "the active molecular", "active molecular components", "components mechanisms", "mechanisms of activation", "and downstream events", "downstream events related", "events related to", "related to the", "to the glycocalyx", "caveolae and", "and cilia are", "cilia are incompletely", "are incompletely characterized", "incompletely characterized so", "characterized so the", "so the annotation", "the annotation here", "annotation here focuses", "here focuses more", "focuses more on", "more on piezo1", "on piezo1 and", "piezo1 and the", "the pecam1:cdh5:kdr complex.
              the", "pecam1:cdh5:kdr complex.
              the force", "complex.
              the force of", "force of the", "the flow on", "flow on the", "on the membrane", "the membrane of", "membrane of the", "of the endothelial", "the endothelial cell", "endothelial cell activates", "cell activates the", "activates the mechanosensitive", "channel piezo1 and", "and indirectly", "indirectly the", "the ion channel", "ion channel trpv4", "channel trpv4 to", "trpv4 to transport", "to transport cations", "cations notably", "calcium from", "from the extracellular", "the extracellular region", "extracellular region to", "region to the", "to the cytosol", "cytosol reviewed", "reviewed in li", "in li et", "li et al.", "et al. 2014", "2014 ranade", "ranade et al.", "2014 fang", "fang et al.", "2021 xiao", "xiao et al.", "2023 . cytosolic", ". cytosolic calcium", "cytosolic calcium activates", "calcium activates the", "activates the protease", "the protease complex", "protease complex calpain2", "complex calpain2 to", "calpain2 to cleave", "to cleave the", "cleave the cytoskeletal", "the cytoskeletal proteins", "cytoskeletal proteins talin1", "proteins talin1 and", "talin1 and vinculin", "vinculin resulting", "resulting in changes", "in changes to", "changes to the", "to the cytoskeleton", "the cytoskeleton that", "cytoskeleton that alter", "that alter the", "alter the shape", "the shape of", "shape of the", "cell miyazaki", "miyazaki et al.", "et al. 2007", "al. 2007 .
              flow", "2007 .
              flow sensitive", ".
              flow sensitive potassium", "sensitive potassium channels", "channels which", "which may include", "may include kir2.1", "include kir2.1 and", "kir2.1 and trek1", "trek1 and", "and chloride channels", "may include lrrc8a", "lrrc8a are", "are also observed", "also observed to", "observed to open", "open however", "however their mechanisms", "their mechanisms of", "of activation and", "activation and downstream", "downstream events are", "events are incompletely", "characterized reviewed", "al. 2021 .
              cytosolic", "2021 .
              cytosolic calcium", ".
              cytosolic calcium activates", "calcium activates pannexin", "activates pannexin channels", "pannexin channels to", "channels to release", "to release atp", "atp wang", "wang et al.", "et al. 2016", "which binds the", "binds the p2ry2", "p2ry2 p2y2", "p2y2 receptor", "receptor on the", "on the cell", "the cell surface", "cell surface in", "surface in an", "in an autocrine", "an autocrine and", "autocrine and paracrine", "and paracrine manner", "paracrine manner and", "manner and thereby", "and thereby activates", "thereby activates galpha", "activates galpha q/11", "q/11 pi3k", "pi3k akt1 signaling.", "akt1 signaling. both", "signaling. both signaling", "both signaling by", "signaling by p2ry2", "by p2ry2 and", "p2ry2 and signaling", "and signaling by", "signaling by a", "by a mechanosensitive", "a mechanosensitive complex", "mechanosensitive complex containing", "complex containing pecam1", "containing pecam1 and", "pecam1 and kdr", "kdr vegfr2", "inferred from mouse", "from mouse homologs", "mouse homologs in", "homologs in tzima", "in tzima et", "tzima et al.", "et al. 2005", "2005 produce", "produce phosphatidylinositol 3", "phosphatidylinositol 3 4", "3 4 5", "4 5 trisphosphate", "trisphosphate pip3", "which binds akt1", "binds akt1 and", "akt1 and enhances", "and enhances the", "enhances the phosphorylation", "the phosphorylation of", "phosphorylation of akt1", "of akt1 on", "akt1 on serine", "on serine 475", "serine 475 by", "475 by the", "by the mtorc2", "the mtorc2 complex.
              through", "mtorc2 complex.
              through a", "complex.
              through a pi3k", "a pi3k independent", "pi3k independent mechanism", "mechanism p2ry2", "p2ry2 signaling and", "signaling and cytosolic", "and cytosolic calcium", "cytosolic calcium activate", "calcium activate the", "activate the kinase", "the kinase pdpk1", "pdpk1 which", "which phosphorylates the", "phosphorylates the kinase", "the kinase pkn2", "pkn2 prk2", "jin et al.", "2021 . phospho", ". phospho pkn2", "phospho pkn2 then", "pkn2 then phosphorylates", "then phosphorylates akt1", "phosphorylates akt1 on", "akt1 on threonine", "on threonine 308", "308 jin", ". phospho t308", "phospho t308 s475", "t308 s475 akt1", "s475 akt1 phosphorylates", "akt1 phosphorylates serine", "phosphorylates serine 1177", "serine 1177 of", "1177 of nos3", "nos3 enos", "enos while", "while phospho pkn2", "phospho pkn2 also", "pkn2 also phosphorylates", "also phosphorylates serine", "phosphorylates serine 1179", "serine 1179 of", "1179 of nos3", "nos3 jin", "causing increased nitric", "increased nitric oxide", "nitric oxide production", "production reviewed", "reviewed in cabou", "in cabou and", "cabou and martinez", "and martinez 2022", "martinez 2022 .
              laminar", "2022 .
              laminar shear", ".
              laminar shear stress", "shear stress increases", "stress increases secretion", "increases secretion of", "secretion of adrenomedullin", "adrenomedullin adm", "vasodilator by", "endothelial cells through", "cells through an", "through an uncharacterized", "an uncharacterized mechanism", "mechanism iring", "iring et al.", "et al. 2019", "al. 2019 .", "2019 . adm", ". adm binds", "adm binds the", "binds the am1", "the am1 receptor", "am1 receptor and", "receptor and signals", "and signals through", "signals through g", "through g alpha", "g alpha s", "and resultant camp", "resultant camp to", "camp to activate", "to activate protein", "activate protein kinase", "protein kinase a", "a pka", "pka to", "to phosphorylate serine", "phosphorylate serine 633", "serine 633 of", "633 of nos3", "nos3 further", "further increasing nitric", "increasing nitric oxide", "production iring", "al. 2019 .
              the", "2019 .
              the sphingosine", ".
              the sphingosine 1", "sphingosine 1 phosphate", "1 phosphate receptor", "phosphate receptor s1pr1", "s1pr1 which", "which couples to", "couples to galpha", "to galpha i1", "i1 and", "and galpha i3", "contributes in a", "in a ligand", "a ligand independent", "ligand independent manner", "independent manner to", "manner to activation", "to activation of", "activation of akt", "of akt and", "akt and nos3", "nos3 however", "however the intermediate", "the intermediate steps", "intermediate steps are", "steps are incompletely", "2021 . other", ". other gpcrs", "other gpcrs such", "gpcrs such as", "such as gpr68", "as gpr68 also", "gpr68 also become", "also become activated", "activated possibly", "possibly through flow", "through flow induced", "flow induced deformation", "induced deformation of", "deformation of the", "of the extracellular", "the extracellular domain", "domain reviewed", "laminar shear stress produced", "shear stress produced by", "stress produced by high", "produced by high fluid", "by high fluid flow", "high fluid flow across", "fluid flow across endothelial", "flow across endothelial cells", "across endothelial cells causes", "endothelial cells causes the", "cells causes the cells", "causes the cells to", "the cells to produce", "cells to produce vasodilatory", "to produce vasodilatory nitric", "produce vasodilatory nitric oxide", "nitric oxide no", "no and to", "and to elongate from", "to elongate from polygonal", "elongate from polygonal to", "from polygonal to ellipsoid", "polygonal to ellipsoid such", "to ellipsoid such that", "ellipsoid such that their", "such that their long", "that their long axes", "their long axes become", "long axes become parallel", "axes become parallel with", "become parallel with direction", "parallel with direction of", "with direction of the", "direction of the flow", "the flow nerem", "flow nerem et", "nerem et al. 1981", "al. 1981 dewey", "1981 dewey et", "dewey et al. 1981", "al. 1981 reviewed", "1981 reviewed in", "reviewed in tamargo et", "in tamargo et al.", "tamargo et al. 2023", "et al. 2023 .", "al. 2023 . nitric", "2023 . nitric oxide", ". nitric oxide produced", "nitric oxide produced by", "oxide produced by endothelial", "produced by endothelial cells", "by endothelial cells modulates", "endothelial cells modulates soluble", "cells modulates soluble guanylyl", "modulates soluble guanylyl cyclase", "soluble guanylyl cyclase and", "guanylyl cyclase and cgmp", "cyclase and cgmp dependent", "and cgmp dependent kinase", "cgmp dependent kinase in", "dependent kinase in surrounding", "kinase in surrounding smooth", "in surrounding smooth muscle", "surrounding smooth muscle cells", "smooth muscle cells to", "muscle cells to cause", "cells to cause vasodilation", "cause vasodilation reviewed", "vasodilation reviewed in", "reviewed in feletou et", "in feletou et al.", "feletou et al. 2008", "al. 2008 2012", "2008 2012 .", "2012 . by optimizing", ". by optimizing blood", "by optimizing blood flow", "optimizing blood flow without", "blood flow without inflammation", "without inflammation the", "inflammation the response", "the response to laminar", "response to laminar shear", "to laminar shear stress", "laminar shear stress is", "shear stress is atheroprotective.
              laminar", "stress is atheroprotective.
              laminar shear", "is atheroprotective.
              laminar shear stress", "atheroprotective.
              laminar shear stress on", "shear stress on endothelial", "stress on endothelial cells", "on endothelial cells is", "endothelial cells is detected", "cells is detected by", "is detected by the", "detected by the glycocalyx", "the glycocalyx caveolae", "cilia the mechanosensitive", "the mechanosensitive ion channel", "mechanosensitive ion channel piezo1", "ion channel piezo1 located", "channel piezo1 located on", "piezo1 located on the", "located on the apex", "on the apex of", "the apex of the", "apex of the cell", "the cell and", "cell and the", "the pecam1:cdh5:kdr pecam1:ve", "pecam1:cdh5:kdr pecam1:ve cadherin:vegfr2", "pecam1:ve cadherin:vegfr2 complex", "cadherin:vegfr2 complex located", "complex located on the", "located on the lateral", "on the lateral surfaces", "the lateral surfaces between", "lateral surfaces between adjacent", "surfaces between adjacent cells", "adjacent cells reviewed", "cells reviewed in", "reviewed in tanaka et", "in tanaka et al.", "tanaka et al. 2021", "et al. 2021 .", "al. 2021 . the", "2021 . the active", ". the active molecular", "the active molecular components", "molecular components mechanisms", "components mechanisms of", "and downstream events related", "downstream events related to", "events related to the", "related to the glycocalyx", "caveolae and cilia", "and cilia are incompletely", "cilia are incompletely characterized", "are incompletely characterized so", "incompletely characterized so the", "characterized so the annotation", "so the annotation here", "the annotation here focuses", "annotation here focuses more", "here focuses more on", "focuses more on piezo1", "more on piezo1 and", "on piezo1 and the", "piezo1 and the pecam1:cdh5:kdr", "and the pecam1:cdh5:kdr complex.
              the", "the pecam1:cdh5:kdr complex.
              the force", "pecam1:cdh5:kdr complex.
              the force of", "complex.
              the force of the", "force of the flow", "of the flow on", "the flow on the", "flow on the membrane", "on the membrane of", "the membrane of the", "membrane of the endothelial", "of the endothelial cell", "the endothelial cell activates", "endothelial cell activates the", "cell activates the mechanosensitive", "activates the mechanosensitive ion", "ion channel piezo1 and", "piezo1 and indirectly", "indirectly the ion", "the ion channel trpv4", "ion channel trpv4 to", "channel trpv4 to transport", "trpv4 to transport cations", "transport cations notably", "cations notably calcium", "notably calcium from", "calcium from the", "from the extracellular region", "the extracellular region to", "extracellular region to the", "region to the cytosol", "the cytosol reviewed", "cytosol reviewed in", "reviewed in li et", "in li et al.", "li et al. 2014", "al. 2014 ranade", "2014 ranade et", "ranade et al. 2014", "al. 2014 fang", "2014 fang et", "fang et al. 2021", "al. 2021 xiao", "2021 xiao et", "xiao et al. 2023", "al. 2023 . cytosolic", "2023 . cytosolic calcium", ". cytosolic calcium activates", "cytosolic calcium activates the", "calcium activates the protease", "activates the protease complex", "the protease complex calpain2", "protease complex calpain2 to", "complex calpain2 to cleave", "calpain2 to cleave the", "to cleave the cytoskeletal", "cleave the cytoskeletal proteins", "the cytoskeletal proteins talin1", "cytoskeletal proteins talin1 and", "proteins talin1 and vinculin", "and vinculin resulting", "vinculin resulting in", "resulting in changes to", "in changes to the", "changes to the cytoskeleton", "to the cytoskeleton that", "the cytoskeleton that alter", "cytoskeleton that alter the", "that alter the shape", "alter the shape of", "the shape of the", "shape of the endothelial", "endothelial cell miyazaki", "cell miyazaki et", "miyazaki et al. 2007", "et al. 2007 .
              flow", "al. 2007 .
              flow sensitive", "2007 .
              flow sensitive potassium", ".
              flow sensitive potassium channels", "potassium channels which", "channels which may", "which may include kir2.1", "may include kir2.1 and", "include kir2.1 and trek1", "and trek1 and", "trek1 and chloride", "chloride channels which", "which may include lrrc8a", "include lrrc8a are", "lrrc8a are also", "are also observed to", "also observed to open", "to open however", "open however their", "however their mechanisms of", "their mechanisms of activation", "mechanisms of activation and", "of activation and downstream", "activation and downstream events", "and downstream events are", "downstream events are incompletely", "events are incompletely characterized", "incompletely characterized reviewed", "characterized reviewed in", "et al. 2021 .
              cytosolic", "al. 2021 .
              cytosolic calcium", "2021 .
              cytosolic calcium activates", ".
              cytosolic calcium activates pannexin", "calcium activates pannexin channels", "activates pannexin channels to", "pannexin channels to release", "channels to release atp", "release atp wang", "atp wang et", "wang et al. 2016", "2016 which", "which binds the p2ry2", "the p2ry2 p2y2", "p2y2 receptor on", "receptor on the cell", "on the cell surface", "the cell surface in", "cell surface in an", "surface in an autocrine", "in an autocrine and", "an autocrine and paracrine", "autocrine and paracrine manner", "and paracrine manner and", "paracrine manner and thereby", "manner and thereby activates", "and thereby activates galpha", "thereby activates galpha q/11", "galpha q/11 pi3k", "q/11 pi3k akt1", "pi3k akt1 signaling. both", "akt1 signaling. both signaling", "signaling. both signaling by", "both signaling by p2ry2", "signaling by p2ry2 and", "by p2ry2 and signaling", "p2ry2 and signaling by", "and signaling by a", "signaling by a mechanosensitive", "by a mechanosensitive complex", "a mechanosensitive complex containing", "mechanosensitive complex containing pecam1", "complex containing pecam1 and", "containing pecam1 and kdr", "and kdr vegfr2", "vegfr2 inferred", "inferred from mouse homologs", "from mouse homologs in", "mouse homologs in tzima", "homologs in tzima et", "in tzima et al.", "tzima et al. 2005", "al. 2005 produce", "2005 produce phosphatidylinositol", "produce phosphatidylinositol 3 4", "phosphatidylinositol 3 4 5", "3 4 5 trisphosphate", "5 trisphosphate pip3", "pip3 which", "which binds akt1 and", "binds akt1 and enhances", "akt1 and enhances the", "and enhances the phosphorylation", "enhances the phosphorylation of", "the phosphorylation of akt1", "phosphorylation of akt1 on", "of akt1 on serine", "akt1 on serine 475", "on serine 475 by", "serine 475 by the", "475 by the mtorc2", "by the mtorc2 complex.
              through", "the mtorc2 complex.
              through a", "mtorc2 complex.
              through a pi3k", "complex.
              through a pi3k independent", "a pi3k independent mechanism", "independent mechanism p2ry2", "mechanism p2ry2 signaling", "p2ry2 signaling and cytosolic", "signaling and cytosolic calcium", "and cytosolic calcium activate", "cytosolic calcium activate the", "calcium activate the kinase", "activate the kinase pdpk1", "kinase pdpk1 which", "pdpk1 which phosphorylates", "which phosphorylates the kinase", "phosphorylates the kinase pkn2", "kinase pkn2 prk2", "prk2 jin", "jin et al. 2021", "al. 2021 . phospho", "2021 . phospho pkn2", ". phospho pkn2 then", "phospho pkn2 then phosphorylates", "pkn2 then phosphorylates akt1", "then phosphorylates akt1 on", "phosphorylates akt1 on threonine", "akt1 on threonine 308", "threonine 308 jin", "308 jin et", "2021 . phospho t308", ". phospho t308 s475", "phospho t308 s475 akt1", "t308 s475 akt1 phosphorylates", "s475 akt1 phosphorylates serine", "akt1 phosphorylates serine 1177", "phosphorylates serine 1177 of", "serine 1177 of nos3", "of nos3 enos", "enos while phospho", "while phospho pkn2 also", "phospho pkn2 also phosphorylates", "pkn2 also phosphorylates serine", "also phosphorylates serine 1179", "phosphorylates serine 1179 of", "serine 1179 of nos3", "of nos3 jin", "nos3 jin et", "2021 causing", "causing increased nitric oxide", "increased nitric oxide production", "oxide production reviewed", "production reviewed in", "reviewed in cabou and", "in cabou and martinez", "cabou and martinez 2022", "and martinez 2022 .
              laminar", "martinez 2022 .
              laminar shear", "2022 .
              laminar shear stress", ".
              laminar shear stress increases", "shear stress increases secretion", "stress increases secretion of", "increases secretion of adrenomedullin", "of adrenomedullin adm", "adm a", "a vasodilator by", "vasodilator by endothelial", "by endothelial cells through", "endothelial cells through an", "cells through an uncharacterized", "through an uncharacterized mechanism", "uncharacterized mechanism iring", "mechanism iring et", "iring et al. 2019", "et al. 2019 .", "al. 2019 . adm", "2019 . adm binds", ". adm binds the", "adm binds the am1", "binds the am1 receptor", "the am1 receptor and", "am1 receptor and signals", "receptor and signals through", "and signals through g", "signals through g alpha", "through g alpha s", "s adenylate", "adenylate cyclase and", "cyclase and resultant", "and resultant camp to", "resultant camp to activate", "camp to activate protein", "to activate protein kinase", "activate protein kinase a", "kinase a pka", "pka to phosphorylate", "to phosphorylate serine 633", "phosphorylate serine 633 of", "serine 633 of nos3", "of nos3 further", "nos3 further increasing", "further increasing nitric oxide", "increasing nitric oxide production", "oxide production iring", "production iring et", "et al. 2019 .
              the", "al. 2019 .
              the sphingosine", "2019 .
              the sphingosine 1", ".
              the sphingosine 1 phosphate", "sphingosine 1 phosphate receptor", "1 phosphate receptor s1pr1", "receptor s1pr1 which", "s1pr1 which couples", "which couples to galpha", "couples to galpha i1", "galpha i1 and", "i1 and galpha", "i3 contributes", "contributes in a ligand", "in a ligand independent", "a ligand independent manner", "ligand independent manner to", "independent manner to activation", "manner to activation of", "to activation of akt", "activation of akt and", "of akt and nos3", "and nos3 however", "nos3 however the", "however the intermediate steps", "the intermediate steps are", "intermediate steps are incompletely", "steps are incompletely characterized", "al. 2021 . other", "2021 . other gpcrs", ". other gpcrs such", "other gpcrs such as", "gpcrs such as gpr68", "such as gpr68 also", "as gpr68 also become", "gpr68 also become activated", "become activated possibly", "activated possibly through", "possibly through flow induced", "through flow induced deformation", "flow induced deformation of", "induced deformation of the", "deformation of the extracellular", "of the extracellular domain", "extracellular domain reviewed", "domain reviewed in", "laminar shear stress produced by", "shear stress produced by high", "stress produced by high fluid", "produced by high fluid flow", "by high fluid flow across", "high fluid flow across endothelial", "fluid flow across endothelial cells", "flow across endothelial cells causes", "across endothelial cells causes the", "endothelial cells causes the cells", "cells causes the cells to", "causes the cells to produce", "the cells to produce vasodilatory", "cells to produce vasodilatory nitric", "to produce vasodilatory nitric oxide", "vasodilatory nitric oxide no", "oxide no and", "no and to elongate", "and to elongate from polygonal", "to elongate from polygonal to", "elongate from polygonal to ellipsoid", "from polygonal to ellipsoid such", "polygonal to ellipsoid such that", "to ellipsoid such that their", "ellipsoid such that their long", "such that their long axes", "that their long axes become", "their long axes become parallel", "long axes become parallel with", "axes become parallel with direction", "become parallel with direction of", "parallel with direction of the", "with direction of the flow", "of the flow nerem", "the flow nerem et", "flow nerem et al.", "et al. 1981 dewey", "al. 1981 dewey et", "1981 dewey et al.", "et al. 1981 reviewed", "al. 1981 reviewed in", "1981 reviewed in tamargo", "reviewed in tamargo et al.", "in tamargo et al. 2023", "tamargo et al. 2023 .", "et al. 2023 . nitric", "al. 2023 . nitric oxide", "2023 . nitric oxide produced", ". nitric oxide produced by", "nitric oxide produced by endothelial", "oxide produced by endothelial cells", "produced by endothelial cells modulates", "by endothelial cells modulates soluble", "endothelial cells modulates soluble guanylyl", "cells modulates soluble guanylyl cyclase", "modulates soluble guanylyl cyclase and", "soluble guanylyl cyclase and cgmp", "guanylyl cyclase and cgmp dependent", "cyclase and cgmp dependent kinase", "and cgmp dependent kinase in", "cgmp dependent kinase in surrounding", "dependent kinase in surrounding smooth", "kinase in surrounding smooth muscle", "in surrounding smooth muscle cells", "surrounding smooth muscle cells to", "smooth muscle cells to cause", "muscle cells to cause vasodilation", "to cause vasodilation reviewed", "cause vasodilation reviewed in", "vasodilation reviewed in feletou", "reviewed in feletou et al.", "in feletou et al. 2008", "et al. 2008 2012", "al. 2008 2012 .", "2008 2012 . by", "2012 . by optimizing blood", ". by optimizing blood flow", "by optimizing blood flow without", "optimizing blood flow without inflammation", "flow without inflammation the", "without inflammation the response", "inflammation the response to", "the response to laminar shear", "response to laminar shear stress", "to laminar shear stress is", "laminar shear stress is atheroprotective.
              laminar", "shear stress is atheroprotective.
              laminar shear", "stress is atheroprotective.
              laminar shear stress", "is atheroprotective.
              laminar shear stress on", "atheroprotective.
              laminar shear stress on endothelial", "shear stress on endothelial cells", "stress on endothelial cells is", "on endothelial cells is detected", "endothelial cells is detected by", "cells is detected by the", "is detected by the glycocalyx", "by the glycocalyx caveolae", "glycocalyx caveolae cilia", "caveolae cilia the", "cilia the mechanosensitive ion", "the mechanosensitive ion channel piezo1", "mechanosensitive ion channel piezo1 located", "ion channel piezo1 located on", "channel piezo1 located on the", "piezo1 located on the apex", "located on the apex of", "on the apex of the", "the apex of the cell", "of the cell and", "the cell and the", "cell and the pecam1:cdh5:kdr", "and the pecam1:cdh5:kdr pecam1:ve", "the pecam1:cdh5:kdr pecam1:ve cadherin:vegfr2", "pecam1:ve cadherin:vegfr2 complex located", "cadherin:vegfr2 complex located on", "complex located on the lateral", "located on the lateral surfaces", "on the lateral surfaces between", "the lateral surfaces between adjacent", "lateral surfaces between adjacent cells", "between adjacent cells reviewed", "adjacent cells reviewed in", "cells reviewed in tanaka", "reviewed in tanaka et al.", "in tanaka et al. 2021", "tanaka et al. 2021 .", "et al. 2021 . the", "al. 2021 . the active", "2021 . the active molecular", ". the active molecular components", "active molecular components mechanisms", "molecular components mechanisms of", "components mechanisms of activation", "and downstream events related to", "downstream events related to the", "events related to the glycocalyx", "to the glycocalyx caveolae", "glycocalyx caveolae and", "caveolae and cilia are", "and cilia are incompletely characterized", "cilia are incompletely characterized so", "are incompletely characterized so the", "incompletely characterized so the annotation", "characterized so the annotation here", "so the annotation here focuses", "the annotation here focuses more", "annotation here focuses more on", "here focuses more on piezo1", "focuses more on piezo1 and", "more on piezo1 and the", "on piezo1 and the pecam1:cdh5:kdr", "piezo1 and the pecam1:cdh5:kdr complex.
              the", "and the pecam1:cdh5:kdr complex.
              the force", "the pecam1:cdh5:kdr complex.
              the force of", "pecam1:cdh5:kdr complex.
              the force of the", "complex.
              the force of the flow", "force of the flow on", "of the flow on the", "the flow on the membrane", "flow on the membrane of", "on the membrane of the", "the membrane of the endothelial", "membrane of the endothelial cell", "of the endothelial cell activates", "the endothelial cell activates the", "endothelial cell activates the mechanosensitive", "cell activates the mechanosensitive ion", "activates the mechanosensitive ion channel", "mechanosensitive ion channel piezo1 and", "channel piezo1 and indirectly", "and indirectly the", "indirectly the ion channel", "the ion channel trpv4 to", "ion channel trpv4 to transport", "channel trpv4 to transport cations", "to transport cations notably", "transport cations notably calcium", "notably calcium from the", "calcium from the extracellular", "from the extracellular region to", "the extracellular region to the", "extracellular region to the cytosol", "to the cytosol reviewed", "the cytosol reviewed in", "cytosol reviewed in li", "reviewed in li et al.", "in li et al. 2014", "et al. 2014 ranade", "al. 2014 ranade et", "2014 ranade et al.", "et al. 2014 fang", "al. 2014 fang et", "2014 fang et al.", "et al. 2021 xiao", "al. 2021 xiao et", "2021 xiao et al.", "xiao et al. 2023 .", "et al. 2023 . cytosolic", "al. 2023 . cytosolic calcium", "2023 . cytosolic calcium activates", ". cytosolic calcium activates the", "cytosolic calcium activates the protease", "calcium activates the protease complex", "activates the protease complex calpain2", "the protease complex calpain2 to", "protease complex calpain2 to cleave", "complex calpain2 to cleave the", "calpain2 to cleave the cytoskeletal", "to cleave the cytoskeletal proteins", "cleave the cytoskeletal proteins talin1", "the cytoskeletal proteins talin1 and", "cytoskeletal proteins talin1 and vinculin", "talin1 and vinculin resulting", "and vinculin resulting in", "vinculin resulting in changes", "resulting in changes to the", "in changes to the cytoskeleton", "changes to the cytoskeleton that", "to the cytoskeleton that alter", "the cytoskeleton that alter the", "cytoskeleton that alter the shape", "that alter the shape of", "alter the shape of the", "the shape of the endothelial", "shape of the endothelial cell", "the endothelial cell miyazaki", "endothelial cell miyazaki et", "cell miyazaki et al.", "miyazaki et al. 2007 .
              flow", "et al. 2007 .
              flow sensitive", "al. 2007 .
              flow sensitive potassium", "2007 .
              flow sensitive potassium channels", "sensitive potassium channels which", "potassium channels which may", "channels which may include", "which may include kir2.1 and", "may include kir2.1 and trek1", "kir2.1 and trek1 and", "and trek1 and chloride", "trek1 and chloride channels", "and chloride channels which", "chloride channels which may", "may include lrrc8a are", "include lrrc8a are also", "lrrc8a are also observed", "are also observed to open", "observed to open however", "to open however their", "open however their mechanisms", "however their mechanisms of activation", "their mechanisms of activation and", "mechanisms of activation and downstream", "of activation and downstream events", "activation and downstream events are", "and downstream events are incompletely", "downstream events are incompletely characterized", "are incompletely characterized reviewed", "incompletely characterized reviewed in", "characterized reviewed in tanaka", "tanaka et al. 2021 .
              cytosolic", "et al. 2021 .
              cytosolic calcium", "al. 2021 .
              cytosolic calcium activates", "2021 .
              cytosolic calcium activates pannexin", ".
              cytosolic calcium activates pannexin channels", "calcium activates pannexin channels to", "activates pannexin channels to release", "pannexin channels to release atp", "to release atp wang", "release atp wang et", "atp wang et al.", "al. 2016 which", "2016 which binds", "binds the p2ry2 p2y2", "p2ry2 p2y2 receptor", "p2y2 receptor on the", "receptor on the cell surface", "on the cell surface in", "the cell surface in an", "cell surface in an autocrine", "surface in an autocrine and", "in an autocrine and paracrine", "an autocrine and paracrine manner", "autocrine and paracrine manner and", "and paracrine manner and thereby", "paracrine manner and thereby activates", "manner and thereby activates galpha", "and thereby activates galpha q/11", "activates galpha q/11 pi3k", "galpha q/11 pi3k akt1", "q/11 pi3k akt1 signaling.", "pi3k akt1 signaling. both signaling", "akt1 signaling. both signaling by", "signaling. both signaling by p2ry2", "both signaling by p2ry2 and", "signaling by p2ry2 and signaling", "by p2ry2 and signaling by", "p2ry2 and signaling by a", "and signaling by a mechanosensitive", "signaling by a mechanosensitive complex", "by a mechanosensitive complex containing", "a mechanosensitive complex containing pecam1", "mechanosensitive complex containing pecam1 and", "complex containing pecam1 and kdr", "pecam1 and kdr vegfr2", "vegfr2 inferred from", "inferred from mouse homologs in", "from mouse homologs in tzima", "mouse homologs in tzima et", "homologs in tzima et al.", "in tzima et al. 2005", "et al. 2005 produce", "al. 2005 produce phosphatidylinositol", "2005 produce phosphatidylinositol 3", "produce phosphatidylinositol 3 4 5", "phosphatidylinositol 3 4 5 trisphosphate", "4 5 trisphosphate pip3", "pip3 which binds", "which binds akt1 and enhances", "binds akt1 and enhances the", "akt1 and enhances the phosphorylation", "and enhances the phosphorylation of", "enhances the phosphorylation of akt1", "the phosphorylation of akt1 on", "phosphorylation of akt1 on serine", "of akt1 on serine 475", "akt1 on serine 475 by", "on serine 475 by the", "serine 475 by the mtorc2", "475 by the mtorc2 complex.
              through", "by the mtorc2 complex.
              through a", "the mtorc2 complex.
              through a pi3k", "mtorc2 complex.
              through a pi3k independent", "complex.
              through a pi3k independent mechanism", "pi3k independent mechanism p2ry2", "independent mechanism p2ry2 signaling", "mechanism p2ry2 signaling and", "p2ry2 signaling and cytosolic calcium", "signaling and cytosolic calcium activate", "and cytosolic calcium activate the", "cytosolic calcium activate the kinase", "calcium activate the kinase pdpk1", "the kinase pdpk1 which", "kinase pdpk1 which phosphorylates", "pdpk1 which phosphorylates the", "which phosphorylates the kinase pkn2", "the kinase pkn2 prk2", "prk2 jin et", "jin et al. 2021 .", "et al. 2021 . phospho", "al. 2021 . phospho pkn2", "2021 . phospho pkn2 then", ". phospho pkn2 then phosphorylates", "phospho pkn2 then phosphorylates akt1", "pkn2 then phosphorylates akt1 on", "then phosphorylates akt1 on threonine", "phosphorylates akt1 on threonine 308", "on threonine 308 jin", "threonine 308 jin et", "308 jin et al.", "al. 2021 . phospho t308", "2021 . phospho t308 s475", ". phospho t308 s475 akt1", "phospho t308 s475 akt1 phosphorylates", "t308 s475 akt1 phosphorylates serine", "s475 akt1 phosphorylates serine 1177", "akt1 phosphorylates serine 1177 of", "phosphorylates serine 1177 of nos3", "1177 of nos3 enos", "nos3 enos while", "enos while phospho pkn2", "while phospho pkn2 also phosphorylates", "phospho pkn2 also phosphorylates serine", "pkn2 also phosphorylates serine 1179", "also phosphorylates serine 1179 of", "phosphorylates serine 1179 of nos3", "1179 of nos3 jin", "of nos3 jin et", "nos3 jin et al.", "al. 2021 causing", "2021 causing increased", "causing increased nitric oxide production", "nitric oxide production reviewed", "oxide production reviewed in", "production reviewed in cabou", "reviewed in cabou and martinez", "in cabou and martinez 2022", "cabou and martinez 2022 .
              laminar", "and martinez 2022 .
              laminar shear", "martinez 2022 .
              laminar shear stress", "2022 .
              laminar shear stress increases", ".
              laminar shear stress increases secretion", "shear stress increases secretion of", "stress increases secretion of adrenomedullin", "secretion of adrenomedullin adm", "adm a vasodilator", "a vasodilator by endothelial", "vasodilator by endothelial cells", "by endothelial cells through an", "endothelial cells through an uncharacterized", "cells through an uncharacterized mechanism", "an uncharacterized mechanism iring", "uncharacterized mechanism iring et", "mechanism iring et al.", "iring et al. 2019 .", "et al. 2019 . adm", "al. 2019 . adm binds", "2019 . adm binds the", ". adm binds the am1", "adm binds the am1 receptor", "binds the am1 receptor and", "the am1 receptor and signals", "am1 receptor and signals through", "receptor and signals through g", "and signals through g alpha", "signals through g alpha s", "alpha s adenylate", "s adenylate cyclase", "adenylate cyclase and resultant", "cyclase and resultant camp", "and resultant camp to activate", "resultant camp to activate protein", "camp to activate protein kinase", "to activate protein kinase a", "protein kinase a pka", "a pka to", "pka to phosphorylate serine", "to phosphorylate serine 633 of", "phosphorylate serine 633 of nos3", "633 of nos3 further", "of nos3 further increasing", "nos3 further increasing nitric", "further increasing nitric oxide production", "nitric oxide production iring", "oxide production iring et", "production iring et al.", "iring et al. 2019 .
              the", "et al. 2019 .
              the sphingosine", "al. 2019 .
              the sphingosine 1", "2019 .
              the sphingosine 1 phosphate", ".
              the sphingosine 1 phosphate receptor", "sphingosine 1 phosphate receptor s1pr1", "phosphate receptor s1pr1 which", "receptor s1pr1 which couples", "s1pr1 which couples to", "which couples to galpha i1", "to galpha i1 and", "galpha i1 and galpha", "i1 and galpha i3", "galpha i3 contributes", "i3 contributes in", "contributes in a ligand independent", "in a ligand independent manner", "a ligand independent manner to", "ligand independent manner to activation", "independent manner to activation of", "manner to activation of akt", "to activation of akt and", "activation of akt and nos3", "akt and nos3 however", "and nos3 however the", "nos3 however the intermediate", "however the intermediate steps are", "the intermediate steps are incompletely", "intermediate steps are incompletely characterized", "et al. 2021 . other", "al. 2021 . other gpcrs", "2021 . other gpcrs such", ". other gpcrs such as", "other gpcrs such as gpr68", "gpcrs such as gpr68 also", "such as gpr68 also become", "as gpr68 also become activated", "also become activated possibly", "become activated possibly through", "activated possibly through flow", "possibly through flow induced deformation", "through flow induced deformation of", "flow induced deformation of the", "induced deformation of the extracellular", "deformation of the extracellular domain", "the extracellular domain reviewed", "extracellular domain reviewed in", "domain reviewed in tanaka" ] }, { "record_id": "GLY_000594_1_2167", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9860927", "r hsa", "hsa 9860927", "r hsa 9860927" ] }, { "record_id": "GLY_000594_1_2167", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "flow shear", "shear stress", "stress activates", "activates signaling", "signaling by", "by piezo1", "piezo1 and", "and integrins", "integrins in", "in endothelial", "endothelial cells", "turbulent oscillatory", "oscillatory disturbed", "disturbed flow", "flow shear stress", "shear stress activates", "stress activates signaling", "activates signaling by", "signaling by piezo1", "by piezo1 and", "piezo1 and integrins", "and integrins in", "integrins in endothelial", "in endothelial cells", "disturbed flow shear", "flow shear stress activates", "shear stress activates signaling", "stress activates signaling by", "activates signaling by piezo1", "signaling by piezo1 and", "by piezo1 and integrins", "piezo1 and integrins in", "and integrins in endothelial", "integrins in endothelial cells", "turbulent oscillatory disturbed", "oscillatory disturbed flow", "disturbed flow shear stress", "flow shear stress activates signaling", "shear stress activates signaling by", "stress activates signaling by piezo1", "activates signaling by piezo1 and", "signaling by piezo1 and integrins", "by piezo1 and integrins in", "piezo1 and integrins in endothelial", "and integrins in endothelial cells", "both turbulent", "flow and", "and low", "low laminar", "laminar flow", "flow across", "across epithelial", "epithelial cells", "cells initiate", "initiate an", "an inflammatory", "inflammatory response", "response that", "that causes", "causes atherosclerosis", "reviewed in", "in rahaman", "rahaman et", "et al.", "al. 2023", "tamargo et", "wang et", "2023 .", ". in", "in vivo", "this process", "process makes", "makes curved", "curved and", "and branched", "branched regions", "regions of", "of arteries", "arteries especially", "especially prone", "prone to", "to atherosclerosis.
              in", "atherosclerosis.
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              through", ".
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              the", ".
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              in", "to atherosclerosis.
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              through", "2018 .
              through an", ".
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              the", "2019 .
              the kinase", ".
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              in", "prone to atherosclerosis.
              in endothelial", "to atherosclerosis.
              in endothelial cells", "endothelial cells fluid", "cells fluid flow", "fluid flow is sensed", "flow is sensed by", "is sensed by mechanoresponsive", "sensed by mechanoresponsive membrane", "by mechanoresponsive membrane localized", "mechanoresponsive membrane localized piezo1", "membrane localized piezo1 channels", "piezo1 channels which", "channels which open", "which open and cause", "open and cause an", "and cause an influx", "cause an influx of", "an influx of cations", "influx of cations including", "of cations including calcium", "cations including calcium ions", "calcium ions ca2+", "ca2+ inferred", "inferred from the mouse", "from the mouse homolog", "the mouse homolog in", "mouse homolog in conte", "homolog in conte et", "in conte et al.", "conte et al. 2010", "et al. 2010 .", "al. 2010 . intracellular", "2010 . intracellular ca2+", ". intracellular ca2+ activates", "intracellular ca2+ activates the", "ca2+ activates the protease", "activates the protease complex", "the protease complex calpain2", "complex calpain2 which", "calpain2 which cleaves", "cleaves vinculin vcl", "vcl a", "a component of the", "component of the peripheral", "of the peripheral cytoskeleton", "the peripheral cytoskeleton located", "peripheral cytoskeleton located between", "cytoskeleton located between integrins", "located between integrins and", "between integrins and actin", "integrins and actin fibers", "actin fibers miyazaki", "fibers miyazaki et", "miyazaki et al. 2007", "al. 2007 2010", "2007 2010 .", "2010 . turbulent flow", ". turbulent flow across", "turbulent flow across endothelial", "flow across endothelial cells", "across endothelial cells also", "endothelial cells also causes", "cells also causes release", "also causes release of", "causes release of atp", "release of atp by", "of atp by an", "atp by an uncharacterized", "by an uncharacterized mechanism", "uncharacterized mechanism albarr\u00e1n", "mechanism albarr\u00e1n ju\u00e1rez", "albarr\u00e1n ju\u00e1rez et al.", "ju\u00e1rez et al. 2018", "et al. 2018 .
              through", "al. 2018 .
              through an", "2018 .
              through an uncharacterized", ".
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              the", "al. 2019 .
              the kinase", "2019 .
              the kinase ptk2", "kinase ptk2 focal", "ptk2 focal adhesion", "adhesion kinase fak", "fak is phosphorylated", "is phosphorylated likely", "phosphorylated likely through", "through autophosphorylation and", "autophosphorylation and then", "and then activates pro", "then activates pro inflammatory", "activates pro inflammatory nf", "pro inflammatory nf \u03bab", "inflammatory nf \u03bab signaling", "nf \u03bab signaling through", "\u03bab signaling through phosphorylation", "signaling through phosphorylation of", "through phosphorylation of chuk", "of chuk ikka", "ikka dwyer", "dwyer et al. 2015", "al. 2015 and", "2015 and rela", "and rela albarr\u00e1n", "rela albarr\u00e1n ju\u00e1rez", "et al. 2018 .", "al. 2018 . ikbke", "2018 . ikbke is", ". ikbke is phosphorylated", "ikbke is phosphorylated by", "is phosphorylated by an", "phosphorylated by an uncharacterized", "an uncharacterized mechanism and", "uncharacterized mechanism and phosphorylates", "mechanism and phosphorylates stat1", "phosphorylates stat1 which", "stat1 which dimerizes", "which dimerizes and transits", "dimerizes and transits to", "pro inflammatory genes such", "inflammatory genes such as", "genes such as nlrp3", "as nlrp3 lv", "nlrp3 lv et", "lv et al. 2024", "et al. 2024 .", "turbulent disturbed flow", "disturbed flow and low", "flow and low laminar flow", "and low laminar flow across", "low laminar flow across epithelial", "laminar flow across epithelial cells", "flow across epithelial cells initiate", "across epithelial cells initiate an", "epithelial cells initiate an inflammatory", "cells initiate an inflammatory response", "initiate an inflammatory response that", "an inflammatory response that causes", "inflammatory response that causes atherosclerosis", "that causes atherosclerosis reviewed", "causes atherosclerosis reviewed in", "atherosclerosis reviewed in rahaman", "reviewed in rahaman et al.", "in rahaman et al. 2023", "et al. 2023 tamargo", "al. 2023 tamargo et", "2023 tamargo et al.", "et al. 2023 wang", "al. 2023 wang et", "2023 wang et al.", "wang et al. 2023 .", "et al. 2023 . in", "al. 2023 . in vivo", ". in vivo this", "in vivo this process", "vivo this process makes", "this process makes curved and", "process makes curved and branched", "makes curved and branched regions", "curved and branched regions of", "and branched regions of arteries", "branched regions of arteries especially", "regions of arteries especially prone", "of arteries especially prone to", "arteries especially prone to atherosclerosis.
              in", "especially prone to atherosclerosis.
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              through", "et al. 2018 .
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              through an uncharacterized", "2018 .
              through an uncharacterized piezo1", ".
              through an uncharacterized piezo1 dependent", "an uncharacterized piezo1 dependent mechanism", "piezo1 dependent mechanism the", "dependent mechanism the phosphatase", "mechanism the phosphatase ptpn1", "the phosphatase ptpn1 ptp1b", "ptpn1 ptp1b is", "ptp1b is activated to", "is activated to dephosphorylate annexin", "activated to dephosphorylate annexin 2", "dephosphorylate annexin 2 anxa2", "anxa2 which relocalizes", "relocalizes with integrins itga5:itgb1", "integrins itga5:itgb1 to", "itga5:itgb1 to lipid rafts", "to lipid rafts in the", "lipid rafts in the cell", "rafts in the cell membrane", "the cell membrane zhang", "cell membrane zhang et", "membrane zhang et al.", "zhang et al. 2020 .", "et al. 2020 . the", "al. 2020 . the integrins", "2020 . the integrins recruit", ". the integrins recruit the", "the integrins recruit the phosphodiesterase", "integrins recruit the phosphodiesterase pde4d5", "recruit the phosphodiesterase pde4d5 and", "the phosphodiesterase pde4d5 and the", "phosphodiesterase pde4d5 and the phosphatase", "pde4d5 and the phosphatase pp2a", "the phosphatase pp2a which", "phosphatase pp2a which activates", "pp2a which activates pde4d5", "which activates pde4d5 by dephosphorylating", "activates pde4d5 by dephosphorylating serine", "pde4d5 by dephosphorylating serine 715", "by dephosphorylating serine 715 and", "dephosphorylating serine 715 and activates", "serine 715 and activates yap1", "715 and activates yap1 by", "and activates yap1 by dephosphorylating", "activates yap1 by dephosphorylating serine", "yap1 by dephosphorylating serine 127", "dephosphorylating serine 127 inferred", "serine 127 inferred from", "127 inferred from mouse", "inferred from mouse homologs in", "from mouse homologs in yun", "mouse homologs in yun et", "homologs in yun et al.", "in yun et al. 2016", "yun et al. 2016 .", "et al. 2016 . activated", "al. 2016 . activated pde4d5", "2016 . activated pde4d5 hydrolyzes", ". activated pde4d5 hydrolyzes camp", "activated pde4d5 hydrolyzes camp and", "pde4d5 hydrolyzes camp and thereby", "hydrolyzes camp and thereby increases", "camp and thereby increases inflammation.", "and thereby increases inflammation. yap1", "thereby increases inflammation. yap1 is", "increases inflammation. yap1 is phosphorylated", "inflammation. yap1 is phosphorylated by", "yap1 is phosphorylated by abl1", "is phosphorylated by abl1 on", "phosphorylated by abl1 on tyrosine", "by abl1 on tyrosine 407", "abl1 on tyrosine 407 and", "on tyrosine 407 and transits", "tyrosine 407 and transits to", "407 and transits to the", "and transits to the nucleus", "transits to the nucleus to", "to the nucleus to activate", "the nucleus to activate pro", "nucleus to activate pro inflammatory", "to activate pro inflammatory genes", "pro inflammatory genes li", "inflammatory genes li et", "genes li et al.", "li et al. 2019 .
              the", "et al. 2019 .
              the kinase", "al. 2019 .
              the kinase ptk2", ".
              the kinase ptk2 focal", "kinase ptk2 focal adhesion", "ptk2 focal adhesion kinase", "focal adhesion kinase fak", "kinase fak is", "is phosphorylated likely through", "phosphorylated likely through autophosphorylation", "likely through autophosphorylation and", "through autophosphorylation and then", "autophosphorylation and then activates", "and then activates pro inflammatory", "then activates pro inflammatory nf", "activates pro inflammatory nf \u03bab", "pro inflammatory nf \u03bab signaling", "inflammatory nf \u03bab signaling through", "nf \u03bab signaling through phosphorylation", "\u03bab signaling through phosphorylation of", "signaling through phosphorylation of chuk", "phosphorylation of chuk ikka", "ikka dwyer et", "et al. 2015 and", "al. 2015 and rela", "and rela albarr\u00e1n ju\u00e1rez", "rela albarr\u00e1n ju\u00e1rez et", "ju\u00e1rez et al. 2018 .", "et al. 2018 . ikbke", "al. 2018 . ikbke is", "2018 . ikbke is phosphorylated", ". ikbke is phosphorylated by", "ikbke is phosphorylated by an", "is phosphorylated by an uncharacterized", "phosphorylated by an uncharacterized mechanism", "by an uncharacterized mechanism and", "an uncharacterized mechanism and phosphorylates", "uncharacterized mechanism and phosphorylates stat1", "and phosphorylates stat1 which", "phosphorylates stat1 which dimerizes", "stat1 which dimerizes and", "which dimerizes and transits to", "dimerizes and transits to the", "activate pro inflammatory genes such", "pro inflammatory genes such as", "inflammatory genes such as nlrp3", "such as nlrp3 lv", "as nlrp3 lv et", "nlrp3 lv et al.", "lv et al. 2024 ." ] }, { "record_id": "GLY_000594_1_2168", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9912481", "r hsa", "hsa 9912481", "r hsa 9912481" ] }, { "record_id": "GLY_000594_1_2168", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "branched chain", "chain ketoacid", "ketoacid dehydrogenase", "dehydrogenase kinase", "kinase deficiency", "branched chain ketoacid", "chain ketoacid dehydrogenase", "ketoacid dehydrogenase kinase", "dehydrogenase kinase deficiency", "branched chain ketoacid dehydrogenase", "chain ketoacid dehydrogenase kinase", "ketoacid dehydrogenase kinase deficiency", "branched chain ketoacid dehydrogenase kinase", "chain ketoacid dehydrogenase kinase deficiency", "is a", "a neurological", "neurological disorder", "disorder that", "that arises", "arises due", "due to", "to mutations", "mutations in", "in branched", "joshi et", "et al", "al 2006", "novarino et", "garcia cazorla", "cazorla et", "tangeraas et", "2023 .", ". bckdk", "bckdk is", "a negative", "negative regulator", "regulator of", "of the", "the branched", "dehydrogenase complex", "the enzyme", "enzyme responsible", "responsible for", "for oxidative", "oxidative decarboxylation", "decarboxylation of", "of branched", "chain amino", "amino acid", "acid derivatives.", "derivatives. bckdk", "bckdk dependent", "dependent phosphorylation", "phosphorylation of", "of serine", "serine residues", "residues in", "in the", "the e1", "e1 alpha", "alpha subunit", "subunit of", "enzyme bckdha", "bckdha inactivates", "inactivates the", "the bckdh", "popov et", "li et", "wynn et", "2004 .
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              inactivating mutations", ".
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              inactivating", "al 2004 .
              inactivating mutations", "2004 .
              inactivating mutations of bckdk", ".
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baumgartner", "2001 baumgartner et al", "baumgartner et al 2001", "et al 2001 .", "al 2001 . mutations", "2001 . mutations in either", ". mutations in either subunit", "mutations in either subunit of", "in either subunit of the", "either subunit of the enzyme", "of the enzyme mccc1", "the enzyme mccc1 and", "enzyme mccc1 and mccc2", "mccc1 and mccc2 are", "and mccc2 are associated", "mccc2 are associated with", "are associated with 3 methylcrotonyl", "associated with 3 methylcrotonyl coa", "with 3 methylcrotonyl coa carboxylase", "coa carboxylase deficiency mccd", "mccd also known", "also known as 3 methylcrotonylglycinuria", "as 3 methylcrotonylglycinuria an", "3 methylcrotonylglycinuria an autosomal", "methylcrotonylglycinuria an autosomal recessive", "an autosomal recessive inborn error", "autosomal recessive inborn error of", "recessive inborn error of metabolism", "inborn error of metabolism characterized", "error of metabolism characterized by", "of metabolism characterized by accumulation", "metabolism characterized by accumulation and", "characterized by accumulation and excretion", "by accumulation and excretion of", "accumulation and excretion of 3", "and excretion of 3 hydroxyvaleric", "excretion of 3 hydroxyvaleric acid", "of 3 hydroxyvaleric acid and", "3 hydroxyvaleric acid and 3", "hydroxyvaleric acid and 3 methylcrotonylglycine", "and 3 methylcrotonylglycine bannwart", "3 methylcrotonylglycine bannwart et", "methylcrotonylglycine bannwart et al", "bannwart et al 1992", "al 1992 lehnert", "1992 lehnert et al", "lehnert et al 1996", "al 1996 baumgartner", "1996 baumgartner et al", "baumgartner et al 2005", "et al 2005 .", "al 2005 . mccd", "2005 . mccd is the", ". mccd is the most", "mccd is the most prevalent", "is the most prevalent organic", "the most prevalent organic aciduria", "most prevalent organic aciduria with", "prevalent organic aciduria with frequencies", "organic aciduria with frequencies ~", "aciduria with frequencies ~ 1:50", "with frequencies ~ 1:50 000", "frequencies ~ 1:50 000 but", "~ 1:50 000 but has", "1:50 000 but has variable", "000 but has variable clinical", "but has variable clinical phenotypes.", "has variable clinical phenotypes. 1", "variable clinical phenotypes. 1 2%", "clinical phenotypes. 1 2% of", "phenotypes. 1 2% of affected", "1 2% of affected individuals", "2% of affected individuals are", "of affected individuals are at", "affected individuals are at risk", "individuals are at risk of", "are at risk of a", "at risk of a severe", "risk of a severe adverse", "of a severe adverse effect", "a severe adverse effect that", "severe adverse effect that manifests", "adverse effect that manifests during", "effect that manifests during the", "that manifests during the neonatal", "manifests during the neonatal period", "during the neonatal period with", "the neonatal period with severe", "neonatal period with severe neurological", "period with severe neurological impairment", "with severe neurological impairment while", "severe neurological impairment while ~10%", "neurological impairment while ~10% of", "impairment while ~10% of affected", "while ~10% of affected individuals", "~10% of affected individuals develop", "of affected individuals develop only", "affected individuals develop only minor", "individuals develop only minor symptoms", "only minor symptoms baumgartner", "minor symptoms baumgartner et", "symptoms baumgartner et al", "al 2001 gallardo", "2001 gallardo et al", "al 2001 gruenert", "2001 gruenert et al", "gruenert et al 2012", "et al 2012 .", "al 2012 . mutations", "2012 . mutations in mccc1", ". mutations in mccc1 and", "mutations in mccc1 and mccc2", "in mccc1 and mccc2 have", "mccc1 and mccc2 have been", "and mccc2 have been identified", "mccc2 have been identified that", "have been identified that affect", "been identified that affect the", "identified that affect the stability", "that affect the stability or", "affect the stability or activity", "the stability or activity of", "stability or activity of the", "or activity of the alpha", "activity of the alpha or", "of the alpha or beta", "the alpha or beta subunit", "or beta subunit occasionally", "beta subunit occasionally by", "subunit occasionally by compromising", "occasionally by compromising the essential", "by compromising the essential biotinylation", "compromising the essential biotinylation of", "the essential biotinylation of the", "essential biotinylation of the protein", "of the protein gallardo", "the protein gallardo et", "protein gallardo et al", "al 2001 grunert", "2001 grunert et al", "grunert et al 2012", "al 2012 fonseca", "2012 fonseca et al", "fonseca et al 2016", "al 2016 dantas", "2016 dantas et al", "dantas et al 2005", "2005 steen et", "steen et al 1999", "al 1999 morscher", "1999 morscher et al", "morscher et al 2012", "2012 baumgartner et", "al 2001 2004", "2001 2004 uematsu", "2004 uematsu et al", "uematsu et al 2007", "al 2007 holzinger", "2007 holzinger et al" ] }, { "record_id": "GLY_000594_1_2174", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9914274", "r hsa", "hsa 9914274", "r hsa 9914274" ] }, { "record_id": "GLY_000594_1_2174", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "3 methylglutaconic", "methylglutaconic aciduria", "3 methylglutaconic aciduria", "mutations in", "in auh", "auh are", "are associated", "associated with", "with 3", "a rare", "rare autosomal", "autosomal recessive", "recessive disorder.", "disorder. auh", "auh catalyzes", "catalyzes the", "the fifth", "fifth step", "step in", "in the", "the catabolism", "catabolism of", "of leucine", "the conversion", "conversion of", "of 3", "3 methylglutaconyl", "methylglutaconyl coa", "coa to", "to 3", "3 hydroxy", "hydroxy methylglutaryl", "methylglutaryl coa", "iljst et", "et al", "ly et", "mack et", "2006 .", ". mutations", "mutations that", "that affect", "affect auh", "auh 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hibch", "valine metabolism hibch mutations", "metabolism hibch mutations result", "hibch mutations result in accumulation", "mutations result in accumulation of", "result in accumulation of toxic", "in accumulation of toxic metabolic", "accumulation of toxic metabolic intermediates", "of toxic metabolic intermediates and", "toxic metabolic intermediates and manifest", "metabolic intermediates and manifest clinically", "intermediates and manifest clinically with", "and manifest clinically with severe", "manifest clinically with severe psychomotor", "clinically with severe psychomotor and", "with severe psychomotor and developmental", "severe psychomotor and developmental delays", "and developmental delays neurodegeneration", "developmental delays neurodegeneration and", "delays neurodegeneration and brain", "and brain lesions characteristic", "brain lesions characteristic of", "lesions characteristic of a", "characteristic of a leigh like", "of a leigh like syndrome", "leigh like syndrome brown", "like syndrome brown et", "syndrome brown et al", "al 2007 ferdinandusse", "2007 ferdinandusse et al", "ferdinandusse et al 2013", "al 2013 peters", "2013 peters et al", "peters et al 2015", "al 2015 reuter", "2015 reuter et al", "reuter et al 2014", "al 2014 d'gama", "2014 d'gama et al", "d'gama et al 2020", "al 2020 reviewed", "2020 reviewed in rahman", "reviewed in rahman et al", "rahman et al 2023", "et al 2023 ." ] }, { "record_id": "GLY_000594_1_2176", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9918440", "r hsa", "hsa 9918440", "r hsa 9918440" ] }, { "record_id": "GLY_000594_1_2176", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective visual", "visual phototransduction", "phototransduction due", "due to", "to rdh12", "rdh12 loss", "loss of", "of function", "defective visual phototransduction", "visual phototransduction due", "phototransduction due to", "due to 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              defects", "cells.

              defects in", "in rdh12", "rdh12 cause", "cause leber", "leber congenital", "congenital amaurosis", "amaurosis type", "type 13", "mim:612712 .", "612712 .", ". lca", "lca defects", "defects are", "are early", "early onset", "onset and", "and severe", "severe retinal", "retinal degenerations", "degenerations that", "that are", "are responsible", "responsible for", "for the", "the most", "most common", "common cause", "cause of", "of congenital", "congenital blindness", "blindness in", "in infants", "infants and", "and children", "janecke et", "et al.", "al. 2004", "perrault et", "2004 .

              defects", ".

              defects in", "cause retinitis", "retinitis pigmentosa", "pigmentosa type", "type 53", "an autosomal", "autosomal recessive", "recessive retinal", "retinal dystrophy", "dystrophy characterised", "characterised by", "by retinal", "retinal pigment", "pigment deposits", "deposits and", "and primary", "primary loss", "of rod", "rod photoreceptor", "photoreceptor cells", "cells followed", "followed by", "by secondary", "secondary loss", "of cone", "cone photoreceptor", "benayoun et", "al. 2009", "2009 .", "retinol dehydrogenase rdh12", "dehydrogenase rdh12 mediates", "rdh12 mediates the", "mediates the reversible", "reversible nadp", "h dependent", "dependent reduction of", "reduction of all", "of all trans", "all trans retinal", "retinal atral", "atral or", "or 11 cis", "11 cis retinal", "retinal 11cral", "11cral to", "to all trans", "all trans retinol", "retinol atrol", "atrol or", "11 cis retinol", "retinol 11crol", "11crol respectively", "respectively in photoreceptor", "in photoreceptor cells.

              defects", "photoreceptor cells.

              defects in", "cells.

              defects in rdh12", "in rdh12 cause", "rdh12 cause leber", "cause leber congenital", "leber congenital amaurosis", "congenital amaurosis type", "amaurosis type 13", "13 lca13", "lca13 mim:612712", "mim:612712 . lca", "612712 . lca", ". lca defects", "lca defects are", "defects are early", "are early onset", "early onset and", "onset and severe", "and severe retinal", "severe retinal degenerations", "retinal degenerations that", "degenerations that are", "that are responsible", "are responsible for", "responsible for the", "for the most", "the most common", "most common cause", "common cause of", "cause of congenital", "of congenital blindness", "congenital blindness in", "blindness in infants", "in infants and", "infants and children", "children janecke", "janecke et al.", "et al. 2004", "2004 perrault", "perrault et al.", "al. 2004 .

              defects", "2004 .

              defects in", ".

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              defects", "in photoreceptor cells.

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              defects", "al. 2004 .

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              an", ".

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              for", ".

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              in", "2021 .

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              an", "2014 .

              an important", ".

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              for", "2023 .

              for a", ".

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              26s", "spermatoproteasome.

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              the 20s", "2013 .

              the 20s cp", ".

              the 20s cp consists", "20s cp consists of", "cp consists of four", "consists of four axially", "of four axially stacked", "four axially stacked heteroheptameric", "axially stacked heteroheptameric rings", "rings two", "two inner and two", "inner and two outer", "and two outer rings", "outer rings reviewed", "rings reviewed in", "hochstrasser 2013 . inner", "2013 . inner rings", ". inner rings contain", "inner rings contain seven", "rings contain seven distinct", "contain seven distinct beta", "seven distinct beta subunits", "beta subunits beta", "subunits beta 1", "1 7 officially", "7 officially psmb1", "officially psmb1 7 in", "psmb1 7 in humans", "in humans where", "humans where beta", "where beta 1 corresponds", "beta 1 corresponds to", "1 corresponds to psmb6", "to psmb6 beta", "psmb6 beta 2", "beta 2 to psmb7", "to psmb7 beta", "psmb7 beta 3", "beta 3 to psmb3", "to psmb3 beta", "psmb3 beta 4", "beta 4 to psmb2", "to psmb2 beta", "psmb2 beta 5", "beta 5 to psmb5", "to psmb5 beta", "psmb5 beta 6", "beta 6 to psmb1", "to psmb1 and", "psmb1 and beta", "and beta 7 to", "beta 7 to psmb4", "psmb4 while", "while the outer rings", "the outer rings contain", "outer rings contain seven", "contain seven distinct alpha", "seven distinct alpha subunits", "alpha subunits alpha1", "subunits alpha1 7", "alpha1 7 officially", "7 officially psma1", "officially psma1 7 in", "psma1 7 in humans", "humans where alpha", "where alpha 1 corresponds", "alpha 1 corresponds to", "1 corresponds to psma6", "to psma6 alpha", "psma6 alpha 2", "alpha 2 to psma2", "to psma2 alpha", "psma2 alpha 3", "alpha 3 to psma4", "to psma4 alpha", "psma4 alpha 4", "alpha 4 to psma7", "to psma7 alpha", "psma7 alpha 5", "alpha 5 to psma5", "to psma5 alpha", "psma5 alpha 6", "alpha 6 to psma1", "to psma1 and", "psma1 and alpha", "and alpha 7 to", "alpha 7 to psma3", "7 to psma3 .

              p28", "to psma3 .

              p28 proteasomes", "psma3 .

              p28 proteasomes consist", ".

              p28 proteasomes consist of", "proteasomes consist of the", "consist of the 20s", "of the 20s cp", "the 20s cp and", "20s cp and a", "cp and a p28", "and a p28 regulatory", "a p28 regulatory particle", "p28 regulatory particle that", "regulatory particle that does", "particle that does not", "that does not have", "does not have a", "not have a ubiquitin", "have a ubiquitin receptor", "a ubiquitin receptor and", "ubiquitin receptor and comes", "receptor and comes in", "and comes in at", "comes in at least", "in at least two", "at least two different", "least two different types", "two different types of", "different types of heptamers:", "types of heptamers: p28", "of heptamers: p28 alpha", "heptamers: p28 alpha beta", "alpha beta composed", "beta composed of", "of psme1 p28alpha", "p28alpha and psme2", "and psme2 p28beta", "p28beta and", "p28 gamma composed", "gamma composed of", "of psme3 p28gamma", "psme3 p28gamma .", "p28gamma . p28 proteasomes", ". p28 proteasomes are", "p28 proteasomes are thought", "proteasomes are thought to", "are thought to be", "thought to be important", "to be important for", "be important for rapid", "important for rapid degradation", "for rapid degradation of", "rapid degradation of misfolded", "degradation of misfolded proteins", "of misfolded proteins under", "misfolded proteins under conditions", "proteins under conditions of", "under conditions of oxidative", "conditions of oxidative stress", "oxidative stress reviewed", "stress reviewed in", "reviewed in thomas et", "in thomas et al.", "thomas et al. 2023", "et al. 2023 .

              in", "al. 2023 .

              in the", "2023 .

              in the immunoproteasome", "the immunoproteasome the", "immunoproteasome the 20s", "the 20s cp inner", "20s cp inner ring", "cp inner ring subunits", "inner ring subunits with", "ring subunits with proteolytic", "subunits with proteolytic activity", "proteolytic activity psmb6", "psmb6 beta 1", "1 psmb7", "psmb7 beta 2", "2 and", "and psmb5 beta", "psmb5 beta 5", "5 are", "are substituted with psmb9", "with psmb9 beta", "psmb9 beta 1i", "1i psmb10", "psmb10 beta 2i", "and psmb8 beta", "psmb8 beta 5i", "5i respectively", "respectively and this", "and this variation of", "this variation of the", "variation of the core", "of the core particle", "the core particle is", "core particle is known", "particle is known as", "is known as 20s", "known as 20s icp.", "as 20s icp. the", "20s icp. the immunoproteasome", "icp. the immunoproteasome generates", "the immunoproteasome generates substrate", "immunoproteasome generates substrate cleavage", "generates substrate cleavage patterns", "substrate cleavage patterns that", "cleavage patterns that enhance", "patterns that enhance loading", "that enhance loading of", "enhance loading of peptides", "loading of peptides onto", "of peptides onto the", "peptides onto the class", "onto the class i", "the class i major", "class i major histocompatibility", "i major histocompatibility complex", "histocompatibility complex mhc", "complex mhc i", "mhc i for", "i for immune", "for immune presentation to", "immune presentation to killer", "presentation to killer t", "to killer t cells", "t cells reviewed", "cells reviewed in", "hochstrasser 2013 . immunoproteasomes", "2013 . immunoproteasomes utilize", ". immunoproteasomes utilize the", "immunoproteasomes utilize the p28", "utilize the p28 regulatory", "the p28 regulatory particle", "regulatory particle chen", "particle chen et", "chen et al. 2021", "et al. 2021 .

              in", "al. 2021 .

              in the", "2021 .

              in the thymoproteasome", "the thymoproteasome expressed", "thymoproteasome expressed in", "expressed in the thymus", "the thymus the", "thymus the 20s", "cp inner ring proteolytic", "inner ring proteolytic subunits", "ring proteolytic subunits psmb6", "subunits psmb6 beta", "1 psbm7", "psbm7 beta 2", "are replaced with psmb9", "beta 2i and", "2i and psmb11", "and psmb11 beta", "psmb11 beta 5t", "5t respectively", "known as 20s tcp.", "as 20s tcp. thymoproteasomes", "20s tcp. thymoproteasomes appear", "tcp. thymoproteasomes appear to", "thymoproteasomes appear to increase", "appear to increase the", "to increase the repertoire", "increase the repertoire of", "the repertoire of self", "repertoire of self peptides", "of self peptides for", "self peptides for positive", "peptides for positive selection", "for positive selection during", "positive selection during t", "selection during t cell", "during t cell development", "t cell development in", "cell development in the", "development in the thymus", "the thymus reviewed", "thymus reviewed in", "2013 . the regulatory", ". the regulatory particle", "the regulatory particle used", "regulatory particle used by", "particle used by thymoproteasomes", "used by thymoproteasomes is", "by thymoproteasomes is not", "thymoproteasomes is not known.

              in", "is not known.

              in the", "not known.

              in the spermatoproteasome", "the spermatoproteasome specifically", "spermatoproteasome specifically expressed", "specifically expressed in differentiating", "expressed in differentiating spermatocytes", "differentiating spermatocytes the", "spermatocytes the outer", "the outer ring subunit", "outer ring subunit psma7", "subunit psma7 alpha", "psma7 alpha 4", "alpha 4 is", "4 is replaced", "is replaced with psma8", "with psma8 alpha", "psma8 alpha 4s", "alpha 4s . spermatoproteasomes", "4s . spermatoproteasomes use", ". spermatoproteasomes use the", "spermatoproteasomes use the 19s", "use the 19s rp", "the 19s rp and", "19s rp and include", "rp and include an", "and include an additional", "include an additional component", "additional component psme4", "pa200 kniepert", "kniepert and groettrup 2014", "and groettrup 2014 .

              an", "groettrup 2014 .

              an important", "2014 .

              an important endogenous", ".

              an important endogenous inhibitor", "important endogenous inhibitor of", "endogenous inhibitor of the", "inhibitor of the catalytic", "of the catalytic activity", "the catalytic activity of", "catalytic activity of 20s", "activity of 20s cp", "of 20s cp is", "20s cp is the", "cp is the protein", "is the protein psmf1", "protein psmf1 pi31", "pi31 hsu", "hsu et al. 2023", "et al. 2023 .

              for", "al. 2023 .

              for a", "2023 .

              for a high", ".

              for a high throughput", "a high throughput study", "high throughput study of", "throughput study of subunit", "study of subunit subunit", "of subunit subunit interactions", "subunit subunit interactions in", "subunit interactions in the", "interactions in the human", "in the human 26s", "the human 26s proteasome", "please refer to chen", "refer to chen et", "to chen et al.", "chen et al. 2008", "al. 2008 and", "2008 and for", "and for the cryogenic", "for the cryogenic electron", "the cryogenic electron microscope", "electron microscope cryo", "microscope cryo em", "cryo em studies", "em studies of", "studies of the human", "of the human 26s", "human 26s proteasome please", "26s proteasome please refer", "proteasome please refer to", "please refer to lu", "refer to lu et", "to lu et al.", "lu et al. 2017", "et al. 2017 and", "al. 2017 and adolf", "2017 and adolf et", "and adolf et al.", "adolf et al. 2024.", "proteasome comes in several varieties.", "comes in several varieties. from", "in several varieties. from the", "several varieties. from the most", "varieties. from the most ubiquitous", "from the most ubiquitous 26s", "the most ubiquitous 26s proteasome", "ubiquitous 26s proteasome through", "26s proteasome through p28", "proteasome through p28 proteasomes", "through p28 proteasomes to", "p28 proteasomes to the", "proteasomes to the tissue", "to the tissue specific proteasomes", "the tissue specific proteasomes such", "tissue specific proteasomes such as", "specific proteasomes such as immunoproteasome", "such as immunoproteasome thymoproteasome", "immunoproteasome thymoproteasome and", "thymoproteasome and spermatoproteasome.

              26s proteasome", "and spermatoproteasome.

              26s proteasome responsible", "spermatoproteasome.

              26s proteasome responsible for", "proteasome responsible for most", "responsible for most aspects of", "for most aspects of ubiquitin", "most aspects of ubiquitin dependent", "aspects of ubiquitin dependent regulatory", "of ubiquitin dependent regulatory and", "ubiquitin dependent regulatory and quality", "dependent regulatory and quality control", "regulatory and quality control protein", "and quality control protein degradation", "quality control protein degradation in", "control protein degradation in cells", "degradation in cells is", "in cells is a", "cells is a 2.6", "is a 2.6 mda protein", "a 2.6 mda protein complex", "2.6 mda protein complex that", "mda protein complex that consists", "protein complex that consists of", "complex that consists of a", "that consists of a barrel", "consists of a barrel shaped", "of a barrel shaped proteolytic", "a barrel shaped proteolytic 20s", "barrel shaped proteolytic 20s core", "shaped proteolytic 20s core particle", "20s core particle 20s", "core particle 20s cp", "20s cp of 28", "cp of 28 subunits", "of 28 subunits capped on", "28 subunits capped on one", "subunits capped on one or", "capped on one or both", "on one or both ends", "one or both ends by", "or both ends by a", "both ends by a 19s", "ends by a 19s regulatory", "by a 19s regulatory particle", "19s regulatory particle 19s", "regulatory particle 19s rp", "19s rp comprised of", "rp comprised of at", "comprised of at least 19", "of at least 19 subunits", "least 19 subunits reviewed", "19 subunits reviewed in", "subunits reviewed in tomko", "reviewed in tomko and hochstrasser", "in tomko and hochstrasser 2013", "tomko and hochstrasser 2013 .", "and hochstrasser 2013 . the", "hochstrasser 2013 . the 19s", "2013 . the 19s rp", "the 19s rp which", "19s rp which consists", "rp which consists of", "which consists of a base", "consists of a base and", "of a base and a", "a base and a lid", "and a lid coordinates", "a lid coordinates substrate", "lid coordinates substrate recognition", "coordinates substrate recognition removal", "substrate recognition removal of", "recognition removal of substrate", "removal of substrate polyubiquitin chains", "substrate polyubiquitin chains and", "polyubiquitin chains and substrate", "chains and substrate unfolding", "and substrate unfolding and translocation", "substrate unfolding and translocation into", "unfolding and translocation into the", "and translocation into the 20s", "translocation into the 20s cp", "into the 20s cp for", "the 20s cp for degradation", "cp for degradation reviewed", "for degradation reviewed in", "degradation reviewed in tomko", "tomko and hochstrasser 2013 .

              the", "and hochstrasser 2013 .

              the 20s", "hochstrasser 2013 .

              the 20s cp", "2013 .

              the 20s cp consists", ".

              the 20s cp consists of", "20s cp consists of four", "cp consists of four axially", "consists of four axially stacked", "of four axially stacked heteroheptameric", "four axially stacked heteroheptameric rings", "heteroheptameric rings two", "rings two inner", "two inner and two outer", "inner and two outer rings", "two outer rings reviewed", "outer rings reviewed in", "rings reviewed in tomko", "and hochstrasser 2013 . inner", "hochstrasser 2013 . inner rings", "2013 . inner rings contain", ". inner rings contain seven", "inner rings contain seven distinct", "rings contain seven distinct beta", "contain seven distinct beta subunits", "distinct beta subunits beta", "beta subunits beta 1", "subunits beta 1 7", "beta 1 7 officially", "1 7 officially psmb1", "7 officially psmb1 7", "officially psmb1 7 in humans", "7 in humans where", "in humans where beta", "humans where beta 1", "where beta 1 corresponds to", "beta 1 corresponds to psmb6", "corresponds to psmb6 beta", "to psmb6 beta 2", "psmb6 beta 2 to", "2 to psmb7 beta", "to psmb7 beta 3", "psmb7 beta 3 to", "3 to psmb3 beta", "to psmb3 beta 4", "psmb3 beta 4 to", "4 to psmb2 beta", "to psmb2 beta 5", "psmb2 beta 5 to", "5 to psmb5 beta", "to psmb5 beta 6", "psmb5 beta 6 to", "6 to psmb1 and", "to psmb1 and beta", "psmb1 and beta 7", "and beta 7 to psmb4", "to psmb4 while", "psmb4 while the", "while the outer rings contain", "the outer rings contain seven", "outer rings contain seven distinct", "rings contain seven distinct alpha", "contain seven distinct alpha subunits", "distinct alpha subunits alpha1", "alpha subunits alpha1 7", "alpha1 7 officially psma1", "7 officially psma1 7", "officially psma1 7 in humans", "in humans where alpha", "humans where alpha 1", "where alpha 1 corresponds to", "alpha 1 corresponds to psma6", "corresponds to psma6 alpha", "to psma6 alpha 2", "psma6 alpha 2 to", "2 to psma2 alpha", "to psma2 alpha 3", "psma2 alpha 3 to", "3 to psma4 alpha", "to psma4 alpha 4", "psma4 alpha 4 to", "4 to psma7 alpha", "to psma7 alpha 5", "psma7 alpha 5 to", "5 to psma5 alpha", "to psma5 alpha 6", "psma5 alpha 6 to", "6 to psma1 and", "to psma1 and alpha", "psma1 and alpha 7", "and alpha 7 to psma3", "alpha 7 to psma3 .

              p28", "7 to psma3 .

              p28 proteasomes", "to psma3 .

              p28 proteasomes consist", "psma3 .

              p28 proteasomes consist of", ".

              p28 proteasomes consist of the", "proteasomes consist of the 20s", "consist of the 20s cp", "of the 20s cp and", "the 20s cp and a", "20s cp and a p28", "cp and a p28 regulatory", "and a p28 regulatory particle", "a p28 regulatory particle that", "p28 regulatory particle that does", "regulatory particle that does not", "particle that does not have", "that does not have a", "does not have a ubiquitin", "not have a ubiquitin receptor", "have a ubiquitin receptor and", "a ubiquitin receptor and comes", "ubiquitin receptor and comes in", "receptor and comes in at", "and comes in at least", "comes in at least two", "in at least two different", "at least two different types", "least two different types of", "two different types of heptamers:", "different types of heptamers: p28", "types of heptamers: p28 alpha", "of heptamers: p28 alpha beta", "p28 alpha beta composed", "alpha beta composed of", "beta composed of psme1", "composed of psme1 p28alpha", "psme1 p28alpha and", "p28beta and p28", "and p28 gamma composed", "p28 gamma composed of", "gamma composed of psme3", "composed of psme3 p28gamma", "of psme3 p28gamma .", "psme3 p28gamma . p28", "p28gamma . p28 proteasomes are", ". p28 proteasomes are thought", "p28 proteasomes are thought to", "proteasomes are thought to be", "are thought to be important", "thought to be important for", "to be important for rapid", "be important for rapid degradation", "important for rapid degradation of", "for rapid degradation of misfolded", "rapid degradation of misfolded proteins", "degradation of misfolded proteins under", "of misfolded proteins under conditions", "misfolded proteins under conditions of", "proteins under conditions of oxidative", "under conditions of oxidative stress", "of oxidative stress reviewed", "oxidative stress reviewed in", "stress reviewed in thomas", "reviewed in thomas et al.", "in thomas et al. 2023", "thomas et al. 2023 .

              in", "et al. 2023 .

              in the", "al. 2023 .

              in the immunoproteasome", ".

              in the immunoproteasome the", "the immunoproteasome the 20s", "immunoproteasome the 20s cp", "the 20s cp inner ring", "20s cp inner ring subunits", "cp inner ring subunits with", "inner ring subunits with proteolytic", "ring subunits with proteolytic activity", "with proteolytic activity psmb6", "activity psmb6 beta", "beta 1 psmb7", "beta 2 and", "2 and psmb5", "and psmb5 beta 5", "beta 5 are", "5 are substituted", "substituted with psmb9 beta", "with psmb9 beta 1i", "beta 1i psmb10", "2i and psmb8", "and psmb8 beta 5i", "beta 5i respectively", "respectively and this variation", "and this variation of the", "this variation of the core", "variation of the core particle", "of the core particle is", "the core particle is known", "core particle is known as", "particle is known as 20s", "is known as 20s icp.", "known as 20s icp. the", "as 20s icp. the immunoproteasome", "20s icp. the immunoproteasome generates", "icp. the immunoproteasome generates substrate", "the immunoproteasome generates substrate cleavage", "immunoproteasome generates substrate cleavage patterns", "generates substrate cleavage patterns that", "substrate cleavage patterns that enhance", "cleavage patterns that enhance loading", "patterns that enhance loading of", "that enhance loading of peptides", "enhance loading of peptides onto", "loading of peptides onto the", "of peptides onto the class", "peptides onto the class i", "onto the class i major", "the class i major histocompatibility", "class i major histocompatibility complex", "major histocompatibility complex mhc", "histocompatibility complex mhc i", "mhc i for immune", "i for immune presentation", "for immune presentation to killer", "immune presentation to killer t", "presentation to killer t cells", "killer t cells reviewed", "t cells reviewed in", "cells reviewed in tomko", "and hochstrasser 2013 . immunoproteasomes", "hochstrasser 2013 . immunoproteasomes utilize", "2013 . immunoproteasomes utilize the", ". immunoproteasomes utilize the p28", "immunoproteasomes utilize the p28 regulatory", "utilize the p28 regulatory particle", "p28 regulatory particle chen", "regulatory particle chen et", "particle chen et al.", "chen et al. 2021 .

              in", "et al. 2021 .

              in the", "al. 2021 .

              in the thymoproteasome", ".

              in the thymoproteasome expressed", "the thymoproteasome expressed in", "thymoproteasome expressed in the", "in the thymus the", "the thymus the 20s", "thymus the 20s cp", "20s cp inner ring proteolytic", "cp inner ring proteolytic subunits", "inner ring proteolytic subunits psmb6", "proteolytic subunits psmb6 beta", "subunits psmb6 beta 1", "beta 1 psbm7", "5 are replaced", "replaced with psmb9 beta", "beta 2i and psmb11", "and psmb11 beta 5t", "beta 5t respectively", "is known as 20s tcp.", "known as 20s tcp. thymoproteasomes", "as 20s tcp. thymoproteasomes appear", "20s tcp. thymoproteasomes appear to", "tcp. thymoproteasomes appear to increase", "thymoproteasomes appear to increase the", "appear to increase the repertoire", "to increase the repertoire of", "increase the repertoire of self", "the repertoire of self peptides", "repertoire of self peptides for", "of self peptides for positive", "self peptides for positive selection", "peptides for positive selection during", "for positive selection during t", "positive selection during t cell", "selection during t cell development", "during t cell development in", "t cell development in the", "cell development in the thymus", "in the thymus reviewed", "the thymus reviewed in", "thymus reviewed in tomko", "hochstrasser 2013 . the regulatory", "2013 . the regulatory particle", ". the regulatory particle used", "the regulatory particle used by", "regulatory particle used by thymoproteasomes", "particle used by thymoproteasomes is", "used by thymoproteasomes is not", "by thymoproteasomes is not known.

              in", "thymoproteasomes is not known.

              in the", "is not known.

              in the spermatoproteasome", "known.

              in the spermatoproteasome specifically", "the spermatoproteasome specifically expressed", "spermatoproteasome specifically expressed in", "specifically expressed in differentiating spermatocytes", "in differentiating spermatocytes the", "differentiating spermatocytes the outer", "spermatocytes the outer ring", "the outer ring subunit psma7", "ring subunit psma7 alpha", "subunit psma7 alpha 4", "alpha 4 is replaced", "4 is replaced with", "replaced with psma8 alpha", "with psma8 alpha 4s", "psma8 alpha 4s .", "alpha 4s . spermatoproteasomes use", "4s . spermatoproteasomes use the", ". spermatoproteasomes use the 19s", "spermatoproteasomes use the 19s rp", "use the 19s rp and", "the 19s rp and include", "19s rp and include an", "rp and include an additional", "and include an additional component", "an additional component psme4", "component psme4 pa200", "pa200 kniepert and", "kniepert and groettrup 2014 .

              an", "and groettrup 2014 .

              an important", "groettrup 2014 .

              an important endogenous", "2014 .

              an important endogenous inhibitor", ".

              an important endogenous inhibitor of", "important endogenous inhibitor of the", "endogenous inhibitor of the catalytic", "inhibitor of the catalytic activity", "of the catalytic activity of", "the catalytic activity of 20s", "catalytic activity of 20s cp", "activity of 20s cp is", "of 20s cp is the", "20s cp is the protein", "cp is the protein psmf1", "the protein psmf1 pi31", "pi31 hsu et", "hsu et al. 2023 .

              for", "et al. 2023 .

              for a", "al. 2023 .

              for a high", "2023 .

              for a high throughput", ".

              for a high throughput study", "a high throughput study of", "high throughput study of subunit", "throughput study of subunit subunit", "study of subunit subunit interactions", "of subunit subunit interactions in", "subunit subunit interactions in the", "subunit interactions in the human", "interactions in the human 26s", "in the human 26s proteasome", "please refer to chen et", "refer to chen et al.", "to chen et al. 2008", "et al. 2008 and", "al. 2008 and for", "2008 and for the", "and for the cryogenic electron", "for the cryogenic electron microscope", "cryogenic electron microscope cryo", "electron microscope cryo em", "cryo em studies of", "em studies of the", "studies of the human 26s", "of the human 26s proteasome", "the human 26s proteasome please", "human 26s proteasome please refer", "26s proteasome please refer to", "proteasome please refer to lu", "please refer to lu et", "refer to lu et al.", "to lu et al. 2017", "lu et al. 2017 and", "et al. 2017 and adolf", "al. 2017 and adolf et", "2017 and adolf et al.", "and adolf et al. 2024." ] }, { "record_id": "GLY_000594_1_2178", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9841251", "r hsa", "hsa 9841251", "r hsa 9841251" ] }, { "record_id": "GLY_000594_1_2178", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "mitochondrial unfolded", "unfolded protein", "protein response", "mitochondrial unfolded protein", "unfolded protein response", "response uprmt", "mitochondrial unfolded protein response", "protein response uprmt", "unfolded protein response uprmt", "misfolded proteins", "proteins in", "in mitochondria", "mitochondria activate", "activate the", "the mitochondrial", "a program", "program of", "of gene", "gene expression", "expression that", "that increases", "increases capacities", "capacities for", "for protein", "protein folding", "folding and", "and protein", "protein degradation", "degradation within", "within the", "the mitochondria", "zhao et", "et al.", "al. 2002", "aldridge et", "al. 2007", "reviewed in", "in cilleros", "cilleros holgado", "holgado et", "al. 2023", "2023 .", ". four", "four interrelated", "interrelated pathways", "pathways that", "that regulate", "regulate the", "the mtupr", "mtupr have", "have been", "been delineated:", "delineated: activation", "activation of", "of heat", "heat shock", "shock factor", "factor 1", "by dissociation", "dissociation from", "from hspa1a", "hspa1a b", "sutandy et", "enhanced translocation", "translocation of", "of atf5", "atf5 to", "to the", "the nucleus", "fiorese et", "al. 2016", "of the", "the estrogen", "estrogen receptor", "receptor alpha", "by phosphorylation", "and activation", "of foxo3", "foxo3 by", "by deacetylation", "in kenny", "kenny and", "and germain", "germain 2017", "munch 2018", "shpilka and", "and haynes", "haynes 2018", "zhou et", "al. 2022", "2022 .
              ", ".
              the", "mtupr appears", "appears to", "to be", "be initiated", "initiated by", "by the", "the accumulation", "accumulation of", "of reactive", "reactive oxygen", "oxygen species", "and mitochondrial", "mitochondrial precursor", "precursor proteins", "in the", "the cytosol", ". the", "the ros", "ros oxidize", "oxidize cysteine", "cysteine residues", "residues on", "on dnaja1", "causing dnaja1", "dnaja1 to", "to displace", "displace hsf1", "hsf1 from", "from the", "the chaperone", "chaperone hspa1a", "hsp70 .", ". hsf1", "hsf1 then", "then transits", "transits to", "and activates", "activates expression", "expression of", "of genes", "genes encoding", "encoding chaperones", "2023 .
              the", ".
              the transcription", "transcription factor", "factor atf5", "which is", "is normally", "normally imported", "imported into", "into mitochondria", "instead accumulates", "accumulates in", "cytosol and", "and transits", "where it", "it acts", "acts with", "with hsf1", "hsf1 to", "to increase", "increase expression", "of chaperone", "chaperone genes", ". atf5", "atf5 may", "may act", "act downstream", "downstream of", "of hsf1", "as atf5", "atf5 is", "is not", "not required", "required to", "to initiate", "initiate the", "2023 .
              ros", ".
              ros also", "also activate", "the protein", "protein kinase", "kinase akt1", "papa and", "germain 2011", "which phosphorylates", "phosphorylates the", "receptor esr1", "campbell et", "al. 2001", "2011 .", ". phosphorylated", "phosphorylated esr1", "esr1 transits", "nucleus and", "independently of", "of estrogen", "activates the", "the expression", "of htra2", "and other", "other genes", "genes involved", "involved in", "in mitochondrial", "mitochondrial homeostasis", "homeostasis as", "as part", "part of", "unfolded response", "2011 .
              through", ".
              through an", "an uncharacterized", "uncharacterized mechanism", "ros cause", "cause increased", "increased expression", "the deacetylase", "deacetylase sirt3", "which directly", "directly or", "or indirectly", "indirectly causes", "causes the", "the deacetylation", "deacetylation of", "the transcription", "factor foxo3.", "foxo3. deacetylated", "deacetylated foxo3", "foxo3 in", "nucleus increases", "increases expression", "the antioxidant", "antioxidant enzymes", "enzymes mitochondrial", "mitochondrial superoxide", "superoxide dismutase", "and peroxisomal", "peroxisomal catalase", "germain 2014", "2014 .", ".
              though", "
              though atf4", "atf4 and", "and chop", "chop are", "are also", "also key", "key regulators", "regulators of", "quiros et", "al. 2017", "the mechanisms", "mechanisms that", "that activate", "activate them", "them in", "in response", "response to", "to unfolded", "protein are", "are not", "not well", "well characterized", "characterized and", "and may", "may involve", "involve the", "the phosphorylation", "phosphorylation of", "the eif2s1", "eif2s1 subunit", "subunit of", "the translation", "translation factor", "factor eif2alpha", "none of", "the four", "four known", "known eif2s1", "eif2s1 kinases", "and pkr", "are required", "required for", "for activation", "of chop", "munch and", "and harper", "harper 2016", "2016 .", "misfolded proteins in", "proteins in mitochondria", "in mitochondria activate", "mitochondria activate the", "activate the mitochondrial", "the mitochondrial unfolded", "response mtupr", "a program of", "program of gene", "of gene expression", "gene expression that", "expression that increases", "that increases capacities", "increases capacities for", "capacities for protein", "for protein folding", "protein folding and", "folding and protein", "and protein degradation", "protein degradation within", "degradation within the", "within the mitochondria", "mitochondria zhao", "zhao et al.", "et al. 2002", "2002 aldridge", "aldridge et al.", "et al. 2007", "2007 reviewed", "reviewed in cilleros", "in cilleros holgado", "cilleros holgado et", "holgado et al.", "et al. 2023", "al. 2023 .", "2023 . four", ". four interrelated", "four interrelated pathways", "interrelated pathways that", "pathways that regulate", "that regulate the", "regulate the mtupr", "the mtupr have", "mtupr have been", "have been delineated:", "been delineated: activation", "delineated: activation of", "activation of heat", "of heat shock", "heat shock factor", "shock factor 1", "1 hsf1", "hsf1 by", "by dissociation from", "dissociation from hspa1a", "from hspa1a b", "b hsp70", "sutandy et al.", "enhanced translocation of", "translocation of atf5", "of atf5 to", "atf5 to the", "to the nucleus", "nucleus fiorese", "fiorese et al.", "et al. 2016", "activation of the", "of the estrogen", "the estrogen receptor", "estrogen receptor alpha", "alpha esr1", "esr1 by", "phosphorylation and", "and activation of", "activation of foxo3", "of foxo3 by", "foxo3 by deacetylation", "deacetylation reviewed", "reviewed in kenny", "in kenny and", "kenny and germain", "and germain 2017", "2017 munch", "2018 shpilka", "shpilka and haynes", "and haynes 2018", "2018 zhou", "zhou et al.", "et al. 2022", "al. 2022 .
              ", "2022 .
              the", ".
              the mtupr", "the mtupr appears", "mtupr appears to", "appears to be", "to be initiated", "be initiated by", "initiated by the", "by the accumulation", "the accumulation of", "accumulation of reactive", "of reactive oxygen", "reactive oxygen species", "species ros", "ros and", "and mitochondrial precursor", "mitochondrial precursor proteins", "precursor proteins in", "proteins in the", "in the cytosol", "cytosol sutandy", "2023 . the", ". the ros", "the ros oxidize", "ros oxidize cysteine", "oxidize cysteine residues", "cysteine residues on", "residues on dnaja1", "dnaja1 causing", "causing dnaja1 to", "dnaja1 to displace", "to displace hsf1", "displace hsf1 from", "hsf1 from the", "from the chaperone", "the chaperone hspa1a", "chaperone hspa1a b", "hsp70 . hsf1", ". hsf1 then", "hsf1 then transits", "then transits to", "transits to the", "nucleus trimerizes", "trimerizes and", "and activates expression", "activates expression of", "expression of genes", "of genes encoding", "genes encoding chaperones", "chaperones sutandy", "al. 2023 .
              the", "2023 .
              the transcription", ".
              the transcription factor", "transcription factor atf5", "atf5 which", "which is normally", "is normally imported", "normally imported into", "imported into mitochondria", "mitochondria instead", "instead accumulates in", "accumulates in the", "the cytosol and", "cytosol and transits", "and transits to", "where it acts", "it acts with", "acts with hsf1", "with hsf1 to", "hsf1 to increase", "to increase expression", "increase expression of", "expression of chaperone", "of chaperone genes", "genes fiorese", "2016 sutandy", "2023 . atf5", ". atf5 may", "atf5 may act", "may act downstream", "act downstream of", "downstream of hsf1", "hsf1 as", "as atf5 is", "atf5 is not", "is not required", "not required to", "required to initiate", "to initiate the", "initiate the mtupr", "mtupr sutandy", "al. 2023 .
              ros", "2023 .
              ros also", ".
              ros also activate", "also activate the", "activate the protein", "the protein kinase", "protein kinase akt1", "akt1 pkb", "papa and germain", "and germain 2011", "which phosphorylates the", "phosphorylates the estrogen", "estrogen receptor esr1", "esr1 campbell", "campbell et al.", "et al. 2001", "2001 papa", "germain 2011 .", "2011 . phosphorylated", ". phosphorylated esr1", "phosphorylated esr1 transits", "esr1 transits to", "the nucleus and", "and independently", "independently of estrogen", "estrogen activates", "activates the expression", "the expression of", "expression of htra2", "htra2 omi", "nrf1 and", "and other genes", "other genes involved", "genes involved in", "involved in mitochondrial", "in mitochondrial homeostasis", "mitochondrial homeostasis as", "homeostasis as part", "as part of", "part of the", "of the mitochondrial", "mitochondrial unfolded response", "response papa", "germain 2011 .
              through", "2011 .
              through an", ".
              through an uncharacterized", "an uncharacterized mechanism", "mechanism ros", "ros cause increased", "cause increased expression", "increased expression of", "expression of the", "of the deacetylase", "the deacetylase sirt3", "sirt3 which", "which directly or", "directly or indirectly", "or indirectly causes", "indirectly causes the", "causes the deacetylation", "the deacetylation of", "deacetylation of the", "of the transcription", "the transcription factor", "transcription factor foxo3.", "factor foxo3. deacetylated", "foxo3. deacetylated foxo3", "deacetylated foxo3 in", "foxo3 in the", "in the nucleus", "the nucleus increases", "nucleus increases expression", "increases expression of", "of the antioxidant", "the antioxidant enzymes", "antioxidant enzymes mitochondrial", "enzymes mitochondrial superoxide", "mitochondrial superoxide dismutase", "dismutase sod2", "sod2 mnsod", "mnsod and", "and peroxisomal catalase", "catalase cat", "cat in", "in the mitochondrial", "and germain 2014", "germain 2014 .", "2014 .
              though", ".
              though atf4", "
              though atf4 and", "atf4 and chop", "and chop are", "chop are also", "are also key", "also key regulators", "key regulators of", "regulators of the", "of the mtupr", "mtupr zhao", "2002 quiros", "quiros et al.", "et al. 2017", "the mechanisms that", "mechanisms that activate", "that activate them", "activate them in", "them in response", "in response to", "response to unfolded", "to unfolded protein", "unfolded protein are", "protein are not", "are not well", "not well characterized", "well characterized and", "characterized and may", "and may involve", "may involve the", "involve the phosphorylation", "the phosphorylation of", "phosphorylation of the", "of the eif2s1", "the eif2s1 subunit", "eif2s1 subunit of", "subunit of the", "of the translation", "the translation factor", "translation factor eif2alpha", "eif2alpha however", "however none", "none of the", "of the four", "the four known", "four known eif2s1", "known eif2s1 kinases", "kinases gcn2", "gcn2 hri", "hri perk", "perk and", "pkr are", "are required for", "required for activation", "for activation of", "activation of chop", "chop munch", "munch and harper", "and harper 2016", "harper 2016 .", "misfolded proteins in mitochondria", "proteins in mitochondria activate", "in mitochondria activate the", "mitochondria activate the mitochondrial", "activate the mitochondrial unfolded", "the mitochondrial unfolded protein", "protein response mtupr", "mtupr a", "a program of gene", "program of gene expression", "of gene expression that", "gene expression that increases", "expression that increases capacities", "that increases capacities for", "increases capacities for protein", "capacities for protein folding", "for protein folding and", "protein folding and protein", "folding and protein degradation", "and protein degradation within", "protein degradation within the", "degradation within the mitochondria", "the mitochondria zhao", "mitochondria zhao et", "zhao et al. 2002", "al. 2002 aldridge", "2002 aldridge et", "aldridge et al. 2007", "al. 2007 reviewed", "2007 reviewed in", "reviewed in cilleros holgado", "in cilleros holgado et", "cilleros holgado et al.", "holgado et al. 2023", "et al. 2023 .", "al. 2023 . four", "2023 . four interrelated", ". four interrelated pathways", "four interrelated pathways that", "interrelated pathways that regulate", "pathways that regulate the", "that regulate the mtupr", "regulate the mtupr have", "the mtupr have been", "mtupr have been delineated:", "have been delineated: activation", "been delineated: activation of", "delineated: activation of heat", "activation of heat shock", "of heat shock factor", "heat shock factor 1", "factor 1 hsf1", "hsf1 by dissociation", "by dissociation from hspa1a", "dissociation from hspa1a b", "hspa1a b hsp70", "hsp70 sutandy", "sutandy et al. 2023", "2023 enhanced", "enhanced translocation of atf5", "translocation of atf5 to", "of atf5 to the", "atf5 to the nucleus", "the nucleus fiorese", "nucleus fiorese et", "fiorese et al. 2016", "2016 activation", "activation of the estrogen", "of the estrogen receptor", "the estrogen receptor alpha", "receptor alpha esr1", "esr1 by phosphorylation", "by phosphorylation and", "phosphorylation and activation", "and activation of foxo3", "activation of foxo3 by", "of foxo3 by deacetylation", "by deacetylation reviewed", "deacetylation reviewed in", "reviewed in kenny and", "in kenny and germain", "kenny and germain 2017", "germain 2017 munch", "2017 munch 2018", "munch 2018 shpilka", "2018 shpilka and", "shpilka and haynes 2018", "haynes 2018 zhou", "2018 zhou et", "zhou et al. 2022", "et al. 2022 .
              ", "al. 2022 .
              the", "2022 .
              the mtupr", ".
              the mtupr appears", "the mtupr appears to", "mtupr appears to be", "appears to be initiated", "to be initiated by", "be initiated by the", "initiated by the accumulation", "by the accumulation of", "the accumulation of reactive", "accumulation of reactive oxygen", "of reactive oxygen species", "oxygen species ros", "ros and mitochondrial", "and mitochondrial precursor proteins", "mitochondrial precursor proteins in", "precursor proteins in the", "proteins in the cytosol", "the cytosol sutandy", "cytosol sutandy et", "al. 2023 . the", "2023 . the ros", ". the ros oxidize", "the ros oxidize cysteine", "ros oxidize cysteine residues", "oxidize cysteine residues on", "cysteine residues on dnaja1", "on dnaja1 causing", "dnaja1 causing dnaja1", "causing dnaja1 to displace", "dnaja1 to displace hsf1", "to displace hsf1 from", "displace hsf1 from the", "hsf1 from the chaperone", "from the chaperone hspa1a", "the chaperone hspa1a b", "b hsp70 .", "hsp70 . hsf1 then", ". hsf1 then transits", "hsf1 then transits to", "then transits to the", "transits to the nucleus", "the nucleus trimerizes", "trimerizes and activates", "and activates expression of", "activates expression of genes", "expression of genes encoding", "of genes encoding chaperones", "encoding chaperones sutandy", "chaperones sutandy et", "et al. 2023 .
              the", "al. 2023 .
              the transcription", "2023 .
              the transcription factor", ".
              the transcription factor atf5", "factor atf5 which", "atf5 which is", "which is normally imported", "is normally imported into", "normally imported into mitochondria", "into mitochondria instead", "mitochondria instead accumulates", "instead accumulates in the", "accumulates in the cytosol", "in the cytosol and", "the cytosol and transits", "cytosol and transits to", "and transits to the", "2016 where", "where it acts with", "it acts with hsf1", "acts with hsf1 to", "with hsf1 to increase", "hsf1 to increase expression", "to increase expression of", "increase expression of chaperone", "expression of chaperone genes", "chaperone genes fiorese", "genes fiorese et", "al. 2016 sutandy", "2016 sutandy et", "al. 2023 . atf5", "2023 . atf5 may", ". atf5 may act", "atf5 may act downstream", "may act downstream of", "act downstream of hsf1", "of hsf1 as", "hsf1 as atf5", "as atf5 is not", "atf5 is not required", "is not required to", "not required to initiate", "required to initiate the", "to initiate the mtupr", "the mtupr sutandy", "mtupr sutandy et", "et al. 2023 .
              ros", "al. 2023 .
              ros also", "2023 .
              ros also activate", ".
              ros also activate the", "also activate the protein", "activate the protein kinase", "the protein kinase akt1", "kinase akt1 pkb", "pkb papa", "papa and germain 2011", "2011 which", "which phosphorylates the estrogen", "phosphorylates the estrogen receptor", "the estrogen receptor esr1", "receptor esr1 campbell", "esr1 campbell et", "campbell et al. 2001", "al. 2001 papa", "2001 papa and", "and germain 2011 .", "germain 2011 . phosphorylated", "2011 . phosphorylated esr1", ". phosphorylated esr1 transits", "phosphorylated esr1 transits to", "esr1 transits to the", "to the nucleus and", "nucleus and independently", "and independently of", "of estrogen activates", "estrogen activates the", "activates the expression of", "the expression of htra2", "of htra2 omi", "omi nrf1", "nrf1 and other", "and other genes involved", "other genes involved in", "genes involved in mitochondrial", "involved in mitochondrial homeostasis", "in mitochondrial homeostasis as", "mitochondrial homeostasis as part", "homeostasis as part of", "as part of the", "part of the mitochondrial", "of the mitochondrial unfolded", "the mitochondrial unfolded response", "unfolded response papa", "response papa and", "and germain 2011 .
              through", "germain 2011 .
              through an", "2011 .
              through an uncharacterized", ".
              through an uncharacterized mechanism", "uncharacterized mechanism ros", "mechanism ros cause", "ros cause increased expression", "cause increased expression of", "increased expression of the", "expression of the deacetylase", "of the deacetylase sirt3", "deacetylase sirt3 which", "sirt3 which directly", "which directly or indirectly", "directly or indirectly causes", "or indirectly causes the", "indirectly causes the deacetylation", "causes the deacetylation of", "the deacetylation of the", "deacetylation of the transcription", "of the transcription factor", "the transcription factor foxo3.", "transcription factor foxo3. deacetylated", "factor foxo3. deacetylated foxo3", "foxo3. deacetylated foxo3 in", "deacetylated foxo3 in the", "foxo3 in the nucleus", "in the nucleus increases", "the nucleus increases expression", "nucleus increases expression of", "increases expression of the", "expression of the antioxidant", "of the antioxidant enzymes", "the antioxidant enzymes mitochondrial", "antioxidant enzymes mitochondrial superoxide", "enzymes mitochondrial superoxide dismutase", "superoxide dismutase sod2", "mnsod and peroxisomal", "peroxisomal catalase cat", "cat in the", "in the mitochondrial unfolded", "papa and germain 2014", "and germain 2014 .", "germain 2014 .
              though", "2014 .
              though atf4", ".
              though atf4 and", "
              though atf4 and chop", "atf4 and chop are", "and chop are also", "chop are also key", "are also key regulators", "also key regulators of", "key regulators of the", "regulators of the mtupr", "the mtupr zhao", "mtupr zhao et", "al. 2002 quiros", "2002 quiros et", "quiros et al. 2017", "2017 the", "the mechanisms that activate", "mechanisms that activate them", "that activate them in", "activate them in response", "them in response to", "in response to unfolded", "response to unfolded protein", "to unfolded protein are", "unfolded protein are not", "protein are not well", "are not well characterized", "not well characterized and", "well characterized and may", "characterized and may involve", "and may involve the", "may involve the phosphorylation", "involve the phosphorylation of", "the phosphorylation of the", "phosphorylation of the eif2s1", "of the eif2s1 subunit", "the eif2s1 subunit of", "eif2s1 subunit of the", "subunit of the translation", "of the translation factor", "the translation factor eif2alpha", "factor eif2alpha however", "however none of", "none of the four", "of the four known", "the four known eif2s1", "four known eif2s1 kinases", "eif2s1 kinases gcn2", "perk and pkr", "and pkr are", "pkr are required", "are required for activation", "required for activation of", "for activation of chop", "of chop munch", "chop munch and", "munch and harper 2016", "and harper 2016 .", "misfolded proteins in mitochondria activate", "proteins in mitochondria activate the", "in mitochondria activate the mitochondrial", "mitochondria activate the mitochondrial unfolded", "activate the mitochondrial unfolded protein", "the mitochondrial unfolded protein response", "unfolded protein response mtupr", "mtupr a program", "a program of gene expression", "program of gene expression that", "of gene expression that increases", "gene expression that increases capacities", "expression that increases capacities for", "that increases capacities for protein", "increases capacities for protein folding", "capacities for protein folding and", "for protein folding and protein", "protein folding and protein degradation", "folding and protein degradation within", "and protein degradation within the", "protein degradation within the mitochondria", "within the mitochondria zhao", "the mitochondria zhao et", "mitochondria zhao et al.", "et al. 2002 aldridge", "al. 2002 aldridge et", "2002 aldridge et al.", "et al. 2007 reviewed", "al. 2007 reviewed in", "2007 reviewed in cilleros", "reviewed in cilleros holgado et", "in cilleros holgado et al.", "cilleros holgado et al. 2023", "holgado et al. 2023 .", "et al. 2023 . four", "al. 2023 . four interrelated", "2023 . four interrelated pathways", ". four interrelated pathways that", "four interrelated pathways that regulate", "interrelated pathways that regulate the", "pathways that regulate the mtupr", "that regulate the mtupr have", "regulate the mtupr have been", "the mtupr have been delineated:", "mtupr have been delineated: activation", "have been delineated: activation of", "been delineated: activation of heat", "delineated: activation of heat shock", "activation of heat shock factor", "of heat shock factor 1", "shock factor 1 hsf1", "1 hsf1 by", "hsf1 by dissociation from", "by dissociation from hspa1a b", "from hspa1a b hsp70", "hsp70 sutandy et", "al. 2023 enhanced", "2023 enhanced translocation", "enhanced translocation of atf5 to", "translocation of atf5 to the", "of atf5 to the nucleus", "to the nucleus fiorese", "the nucleus fiorese et", "nucleus fiorese et al.", "al. 2016 activation", "2016 activation of", "activation of the estrogen receptor", "of the estrogen receptor alpha", "estrogen receptor alpha esr1", "alpha esr1 by", "by phosphorylation and activation", "phosphorylation and activation of", "and activation of foxo3 by", "activation of foxo3 by deacetylation", "foxo3 by deacetylation reviewed", "by deacetylation reviewed in", "deacetylation reviewed in kenny", "reviewed in kenny and germain", "in kenny and germain 2017", "and germain 2017 munch", "germain 2017 munch 2018", "munch 2018 shpilka and", "2018 shpilka and haynes", "and haynes 2018 zhou", "haynes 2018 zhou et", "2018 zhou et al.", "zhou et al. 2022 .
              ", "et al. 2022 .
              the", "al. 2022 .
              the mtupr", "2022 .
              the mtupr appears", ".
              the mtupr appears to", "the mtupr appears to be", "mtupr appears to be initiated", "appears to be initiated by", "to be initiated by the", "be initiated by the accumulation", "initiated by the accumulation of", "by the accumulation of reactive", "the accumulation of reactive oxygen", "accumulation of reactive oxygen species", "reactive oxygen species ros", "species ros and", "ros and mitochondrial precursor", "and mitochondrial precursor proteins in", "mitochondrial precursor proteins in the", "precursor proteins in the cytosol", "in the cytosol sutandy", "the cytosol sutandy et", "cytosol sutandy et al.", "sutandy et al. 2023 .", "et al. 2023 . the", "al. 2023 . the ros", "2023 . the ros oxidize", ". the ros oxidize cysteine", "the ros oxidize cysteine residues", "ros oxidize cysteine residues on", "oxidize cysteine residues on dnaja1", "residues on dnaja1 causing", "on dnaja1 causing dnaja1", "dnaja1 causing dnaja1 to", "causing dnaja1 to displace hsf1", "dnaja1 to displace hsf1 from", "to displace hsf1 from the", "displace hsf1 from the chaperone", "hsf1 from the chaperone hspa1a", "from the chaperone hspa1a b", "chaperone hspa1a b hsp70", "hspa1a b hsp70 .", "b hsp70 . hsf1", "hsp70 . hsf1 then transits", ". hsf1 then transits to", "hsf1 then transits to the", "then transits to the nucleus", "to the nucleus trimerizes", "nucleus trimerizes and", "trimerizes and activates expression", "and activates expression of genes", "activates expression of genes encoding", "expression of genes encoding chaperones", "genes encoding chaperones sutandy", "encoding chaperones sutandy et", "chaperones sutandy et al.", "sutandy et al. 2023 .
              the", "et al. 2023 .
              the transcription", "al. 2023 .
              the transcription factor", "2023 .
              the transcription factor atf5", "transcription factor atf5 which", "factor atf5 which is", "atf5 which is normally", "which is normally imported into", "is normally imported into mitochondria", "imported into mitochondria instead", "into mitochondria instead accumulates", "mitochondria instead accumulates in", "instead accumulates in the cytosol", "accumulates in the cytosol and", "in the cytosol and transits", "the cytosol and transits to", "cytosol and transits to the", "and transits to the nucleus", "al. 2016 where", "2016 where it", "where it acts with hsf1", "it acts with hsf1 to", "acts with hsf1 to increase", "with hsf1 to increase expression", "hsf1 to increase expression of", "to increase expression of chaperone", "increase expression of chaperone genes", "of chaperone genes fiorese", "chaperone genes fiorese et", "genes fiorese et al.", "et al. 2016 sutandy", "al. 2016 sutandy et", "2016 sutandy et al.", "et al. 2023 . atf5", "al. 2023 . atf5 may", "2023 . atf5 may act", ". atf5 may act downstream", "atf5 may act downstream of", "may act downstream of hsf1", "downstream of hsf1 as", "of hsf1 as atf5", "hsf1 as atf5 is", "as atf5 is not required", "atf5 is not required to", "is not required to initiate", "not required to initiate the", "required to initiate the mtupr", "initiate the mtupr sutandy", "the mtupr sutandy et", "mtupr sutandy et al.", "sutandy et al. 2023 .
              ros", "et al. 2023 .
              ros also", "al. 2023 .
              ros also activate", "2023 .
              ros also activate the", ".
              ros also activate the protein", "also activate the protein kinase", "activate the protein kinase akt1", "protein kinase akt1 pkb", "pkb papa and", "germain 2011 which", "2011 which phosphorylates", "which phosphorylates the estrogen receptor", "phosphorylates the estrogen receptor esr1", "estrogen receptor esr1 campbell", "receptor esr1 campbell et", "esr1 campbell et al.", "et al. 2001 papa", "al. 2001 papa and", "2001 papa and germain", "papa and germain 2011 .", "and germain 2011 . phosphorylated", "germain 2011 . phosphorylated esr1", "2011 . phosphorylated esr1 transits", ". phosphorylated esr1 transits to", "phosphorylated esr1 transits to the", "esr1 transits to the nucleus", "transits to the nucleus and", "the nucleus and independently", "nucleus and independently of", "and independently of estrogen", "independently of estrogen activates", "of estrogen activates the", "estrogen activates the expression", "activates the expression of htra2", "expression of htra2 omi", "nrf1 and other genes", "and other genes involved in", "other genes involved in mitochondrial", "genes involved in mitochondrial homeostasis", "involved in mitochondrial homeostasis as", "in mitochondrial homeostasis as part", "mitochondrial homeostasis as part of", "homeostasis as part of the", "as part of the mitochondrial", "part of the mitochondrial unfolded", "of the mitochondrial unfolded response", "mitochondrial unfolded response papa", "unfolded response papa and", "response papa and germain", "papa and germain 2011 .
              through", "and germain 2011 .
              through an", "germain 2011 .
              through an uncharacterized", "2011 .
              through an uncharacterized mechanism", "an uncharacterized mechanism ros", "uncharacterized mechanism ros cause", "mechanism ros cause increased", "ros cause increased expression of", "cause increased expression of the", "increased expression of the deacetylase", "expression of the deacetylase sirt3", "the deacetylase sirt3 which", "deacetylase sirt3 which directly", "sirt3 which directly or", "which directly or indirectly causes", "directly or indirectly causes the", "or indirectly causes the deacetylation", "indirectly causes the deacetylation of", "causes the deacetylation of the", "the deacetylation of the transcription", "deacetylation of the transcription factor", "of the transcription factor foxo3.", "the transcription factor foxo3. deacetylated", "transcription factor foxo3. deacetylated foxo3", "factor foxo3. deacetylated foxo3 in", "foxo3. deacetylated foxo3 in the", "deacetylated foxo3 in the nucleus", "foxo3 in the nucleus increases", "in the nucleus increases expression", "the nucleus increases expression of", "nucleus increases expression of the", "increases expression of the antioxidant", "expression of the antioxidant enzymes", "of the antioxidant enzymes mitochondrial", "the antioxidant enzymes mitochondrial superoxide", "antioxidant enzymes mitochondrial superoxide dismutase", "mitochondrial superoxide dismutase sod2", "dismutase sod2 mnsod", "sod2 mnsod and", "mnsod and peroxisomal catalase", "and peroxisomal catalase cat", "catalase cat in", "cat in the mitochondrial", "in the mitochondrial unfolded response", "papa and germain 2014 .", "and germain 2014 .
              though", "germain 2014 .
              though atf4", "2014 .
              though atf4 and", ".
              though atf4 and chop", "
              though atf4 and chop are", "atf4 and chop are also", "and chop are also key", "chop are also key regulators", "are also key regulators of", "also key regulators of the", "key regulators of the mtupr", "of the mtupr zhao", "the mtupr zhao et", "mtupr zhao et al.", "et al. 2002 quiros", "al. 2002 quiros et", "2002 quiros et al.", "al. 2017 the", "2017 the mechanisms", "the mechanisms that activate them", "mechanisms that activate them in", "that activate them in response", "activate them in response to", "them in response to unfolded", "in response to unfolded protein", "response to unfolded protein are", "to unfolded protein are not", "unfolded protein are not well", "protein are not well characterized", "are not well characterized and", "not well characterized and may", "well characterized and may involve", "characterized and may involve the", "and may involve the phosphorylation", "may involve the phosphorylation of", "involve the phosphorylation of the", "the phosphorylation of the eif2s1", "phosphorylation of the eif2s1 subunit", "of the eif2s1 subunit of", "the eif2s1 subunit of the", "eif2s1 subunit of the translation", "subunit of the translation factor", "of the translation factor eif2alpha", "translation factor eif2alpha however", "eif2alpha however none", "however none of the", "none of the four known", "of the four known eif2s1", "the four known eif2s1 kinases", "known eif2s1 kinases gcn2", "kinases gcn2 hri", "gcn2 hri perk", "hri perk and", "and pkr are required", "pkr are required for", "are required for activation of", "required for activation of chop", "activation of chop munch", "of chop munch and", "chop munch and harper", "munch and harper 2016 ." ] }, { "record_id": "GLY_000594_1_2179", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9918436", "r hsa", "hsa 9918436", "r hsa 9918436" ] }, { "record_id": "GLY_000594_1_2179", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective visual", "visual phototransduction", "phototransduction due", "due to", "to opn1mw", "opn1mw loss", "loss of", "of function", "defective visual phototransduction", "visual phototransduction due", "phototransduction due to", "due to opn1mw", "to opn1mw loss", "opn1mw loss of", "loss of function", "defective visual phototransduction due", "visual phototransduction due to", "phototransduction due to opn1mw", "due to opn1mw loss", "to opn1mw loss of", "opn1mw loss of function", "defective visual phototransduction due to", "visual phototransduction due to opn1mw", "phototransduction due to opn1mw loss", "due to opn1mw loss of", "to opn1mw loss of function", "normal human", "human colour", "colour vision", "vision is", "is trichromatic", "based on", "on 3", "3 types", "types of", "of cones", "cones that", "that are", "are maximally", "maximally sensitive", "sensitive to", "to light", "light at", "at approximately", "approximately 420", "420 nm", "blue cones", "530 nm", "green cones", "and 560", "560 nm", "red cones", "cones .", ". neural", "neural circuits", "circuits compare", "compare light", "light absorbed", "absorbed by", "by these", "these 3", "3 cone", "cone types", "types to", "to perceive", "perceive those", "those primary", "primary colours", "colours and", "and combinations", "combinations of", "of them.", "them. colour", "vision deficiencies", "deficiencies result", "result from", "from genetic", "genetic mutations", "mutations that", "that affect", "affect the", "the expression", "expression of", "of the", "the full", "full complement", "complement of", "of cone", "cone photoreceptors", "photoreceptors and", "and are", "are classified", "classified by", "by severity", "severity of", "of deficiency", "see reviews", "reviews deeb", "deeb 2005", "simunovic 2010", "2010 .

              deutan", ".

              deutan colourblindness", "partial colorblindness", "green colourblindness", "is caused", "caused by", "by mutations", "mutations in", "in the", "the opn1mw", "opn1mw gene", "gene which", "which encodes", "encodes green", "green cones.", "cones. in", "in european", "european populations", "red green", "colourblindness is", "is prevelant", "prevelant in", "in 8%", "8% of", "of males", "males and", "and 0.5%", "0.5% of", "of females.", "females. this", "this frequency", "frequency is", "is lower", "lower in", "in non", "non european", "2005 .

              defects", ".

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              deutan", "2010 .

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              defects", "2005 .

              defects in", ".

              defects in opn1mw", "in opn1mw also", "opn1mw also cause", "also cause x", "cause x linked", "x linked cone", "linked cone dystrophy", "cone dystrophy type", "dystrophy type 5", "5 cod5", "cod5 mim:303700", "a retinal dystrophy", "retinal dystrophy characterized", "dystrophy characterized by", "characterized by progressive", "by progressive degeneration", "progressive degeneration of", "degeneration of cone", "cone photoreceptors but", "photoreceptors but with", "but with preserved", "with preserved rod", "preserved rod function.", "normal human colour vision", "human colour vision is", "colour vision is trichromatic", "is trichromatic based", "trichromatic based on", "based on 3 types", "on 3 types of", "3 types of cones", "types of cones that", "of cones that are", "cones that are maximally", "that are maximally sensitive", "are maximally sensitive to", "maximally sensitive to light", "sensitive to light at", "to light at approximately", "light at approximately 420", "at approximately 420 nm", "420 nm blue", "nm blue cones", "cones 530", "530 nm green", "nm green cones", "cones and", "560 nm red", "nm red cones", "red cones . neural", "cones . neural circuits", ". neural circuits compare", "neural circuits compare light", "circuits compare light absorbed", "compare light absorbed by", "light absorbed by these", "absorbed by these 3", "by these 3 cone", "these 3 cone types", "3 cone types to", "cone types to perceive", "types to perceive those", "to perceive those primary", "perceive those primary colours", "those primary colours and", "primary colours and combinations", "colours and combinations of", "and combinations of them.", "combinations of them. colour", "of them. colour vision", "them. colour vision deficiencies", "colour vision deficiencies result", "vision deficiencies result from", "deficiencies result from genetic", "result from genetic mutations", "from genetic mutations that", "genetic mutations that affect", "mutations that affect the", "that affect the expression", "affect the expression of", "the expression of the", "expression of the full", "of the full complement", "the full complement of", "full complement of cone", "complement of cone photoreceptors", "of cone photoreceptors and", "cone photoreceptors and are", "photoreceptors and are classified", "and are classified by", "are classified by severity", "classified by severity of", "by severity of deficiency", "of deficiency see", "deficiency see reviews", "see reviews deeb 2005", "deeb 2005 simunovic", "2005 simunovic 2010", "simunovic 2010 .

              deutan colourblindness", ".

              deutan colourblindness dcb", "deuteranopia partial colorblindness", "partial colorblindness green", "colorblindness green colourblindness", "green colourblindness mim:303800", "mim:303800 is caused", "303800 is caused", "is caused by mutations", "caused by mutations in", "by mutations in the", "mutations in the opn1mw", "in the opn1mw gene", "the opn1mw gene which", "opn1mw gene which encodes", "gene which encodes green", "which encodes green cones.", "encodes green cones. in", "green cones. in european", "cones. in european populations", "european populations red", "populations red green", "red green colourblindness is", "green colourblindness is prevelant", "colourblindness is prevelant in", "is prevelant in 8%", "prevelant in 8% of", "in 8% of males", "8% of males and", "of males and 0.5%", "males and 0.5% of", "and 0.5% of females.", "0.5% of females. this", "of females. this frequency", "females. this frequency is", "this frequency is lower", "frequency is lower in", "is lower in non", "lower in non european", "in non european populations", "european populations deeb", "populations deeb 2005", "deeb 2005 .

              defects in", "2005 .

              defects in opn1mw", ".

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              deutan", "2010 .

              deutan colourblindness dcb", "colourblindness dcb deuteranopia", "dcb deuteranopia partial", "partial colorblindness green colourblindness", "colourblindness mim:303800 is", "mim:303800 is caused by", "303800 is caused by", "is caused by mutations in", "caused by mutations in the", "by mutations in the opn1mw", "mutations in the opn1mw gene", "in the opn1mw gene which", "the opn1mw gene which encodes", "opn1mw gene which encodes green", "gene which encodes green cones.", "which encodes green cones. in", "encodes green cones. in european", "green cones. in european populations", "in european populations red", "european populations red green", "populations red green colourblindness", "red green colourblindness is prevelant", "green colourblindness is prevelant in", "colourblindness is prevelant in 8%", "is prevelant in 8% of", "prevelant in 8% of males", "in 8% of males and", "8% of males and 0.5%", "of males and 0.5% of", "males and 0.5% of females.", "and 0.5% of females. this", "0.5% of females. this frequency", "of females. this frequency is", "females. this frequency is lower", "this frequency is lower in", "frequency is lower in non", "is lower in non european", "lower in non european populations", "non european populations deeb", "european populations deeb 2005", "populations deeb 2005 .

              defects", "deeb 2005 .

              defects in opn1mw", "2005 .

              defects in opn1mw also", ".

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              tritan", "blue yellow", "blue colourblindness", "deficiencies are", "are rare", "1 in", "in 500", "went &", "& pronk", "pronk 1985", "compared to", "to those", "those involving", "involving green", "and red", "red cone", "cone deficiencies.", "deficiencies. the", "the first", "first report", "report of", "of tritan", "tritan defects", "defects was", "was in", "in 1952", "wright 1952", "1952 .", ". tritan", "tritan deficiencies", "are inherited", "inherited as", "as autosomal", "autosomal dominant", "dominant traits", "kalmus 1955", "are a", "a result", "result of", "of missense", "missense mutations", "mutations in", "in the", "the blue", "blue cone", "cone photopigment", "photopigment gene", "gene opn1sw", "leading to", "to amino", "amino acid", "acid substitutions", "substitutions in", "the protein", "protein sequence.", "sequence. tritan", "defects are", "are characterized", "characterized by", "by a", "a selective", "selective deficiency", "deficiency of", "of blue", "blue spectral", "spectral sensitivity", "weitz et", "et al.", "al. 1992", "1992 .", "normal human colour", "human colour vision", "colour vision is", "vision is trichromatic", "trichromatic based", "based on 3", "on 3 types", "3 types of", "types of cones", "of cones that", "cones that are", "that are maximally", "are maximally sensitive", "maximally sensitive to", "sensitive to light", "to light at", "light at approximately", "at approximately 420", "approximately 420 nm", "nm blue", "nm green", "and 560 nm", "nm red", "red cones .", "cones . neural", ". neural circuits", "neural circuits compare", "circuits compare light", "compare light absorbed", "light absorbed by", "absorbed by these", "by these 3", "these 3 cone", "3 cone types", "cone types to", "types to perceive", "to perceive those", "perceive those primary", "those primary colours", "primary colours and", "colours and combinations", "and combinations of", "combinations of them.", "of them. colour", "them. colour vision", "colour vision deficiencies", "vision deficiencies result", "deficiencies result from", "result from genetic", "from genetic mutations", "genetic mutations that", "mutations that affect", "that affect the", "affect the expression", "the expression of", "expression of the", "of the full", "the full complement", "full complement of", "complement of cone", "of cone photoreceptors", "cone photoreceptors and", "photoreceptors and are", "and are classified", "are classified by", "classified by severity", "by severity of", "severity of deficiency", "deficiency see", "see reviews deeb", "reviews deeb 2005", "2005 simunovic", "simunovic 2010 .

              tritan", ".

              tritan blue", "yellow blue", "colourblindness tritanopia", "tritanopia mim:190900", "mim:190900 deficiencies", "190900 deficiencies", "deficiencies are rare", "rare 1", "1 in 500", "went & pronk", "& pronk 1985", "1985 compared", "compared to those", "to those involving", "those involving green", "green and", "and red cone", "red cone deficiencies.", "cone deficiencies. the", "deficiencies. the first", "the first report", "first report of", "report of tritan", "of tritan defects", "tritan defects was", "defects was in", "was in 1952", "1952 wright", "wright 1952 .", "1952 . tritan", ". tritan deficiencies", "tritan deficiencies are", "deficiencies are inherited", "are inherited as", "inherited as autosomal", "as autosomal dominant", "autosomal dominant traits", "traits kalmus", "1955 and", "and are a", "are a result", "a result of", "result of missense", "of missense mutations", "missense mutations in", "mutations in the", "in the blue", "the blue cone", "blue cone photopigment", "cone photopigment gene", "photopigment gene opn1sw", "opn1sw leading", "leading to amino", "to amino acid", "amino acid substitutions", "acid substitutions in", "substitutions in the", "in the protein", "the protein sequence.", "protein sequence. tritan", "sequence. tritan defects", "tritan defects are", "defects are characterized", "are characterized by", "characterized by a", "by a selective", "a selective deficiency", "selective deficiency of", "deficiency of blue", "of blue spectral", "blue spectral sensitivity", "sensitivity weitz", "weitz et al.", "et al. 1992", "al. 1992 .", "normal human colour vision", "human colour vision is", "colour vision is trichromatic", "is trichromatic based", "trichromatic based on", "based on 3 types", "on 3 types of", "3 types of cones", "types of cones that", "of cones that are", "cones that are maximally", "that are maximally sensitive", "are maximally sensitive to", "maximally sensitive to light", "sensitive to light at", "to light at approximately", "light at approximately 420", "at approximately 420 nm", "420 nm blue", "nm blue cones", "cones 530", "530 nm green", "nm green cones", "cones and", "560 nm red", "nm red cones", "red cones . neural", "cones . neural circuits", ". neural circuits compare", "neural circuits compare light", "circuits compare light absorbed", "compare light absorbed by", "light absorbed by these", "absorbed by these 3", "by these 3 cone", "these 3 cone types", "3 cone types to", "cone types to perceive", "types to perceive those", "to perceive those primary", "perceive those primary colours", "those primary colours and", "primary colours and combinations", "colours and combinations of", "and combinations of them.", "combinations of them. colour", "of them. colour vision", "them. colour vision deficiencies", "colour vision deficiencies result", "vision deficiencies result from", "deficiencies result from genetic", "result from genetic mutations", "from genetic mutations that", "genetic mutations that affect", "mutations that affect the", "that affect the expression", "affect the expression of", "the expression of the", "expression of the full", "of the full complement", "the full complement of", "full complement of cone", "complement of cone photoreceptors", "of cone photoreceptors and", "cone photoreceptors and are", "photoreceptors and are classified", "and are classified by", "are classified by severity", "classified by severity of", "by severity of deficiency", "of deficiency see", "deficiency see reviews", "see reviews deeb 2005", "deeb 2005 simunovic", "2005 simunovic 2010", "2010 .

              tritan blue", ".

              tritan blue yellow", "blue yellow blue", "yellow blue colourblindness", "blue colourblindness tritanopia", "mim:190900 deficiencies are", "190900 deficiencies are", "are rare 1", "rare 1 in", "500 went", "went & pronk 1985", "pronk 1985 compared", "1985 compared to", "compared to those involving", "to those involving green", "involving green and", "green and red", "and red cone deficiencies.", "red cone deficiencies. the", "cone deficiencies. the first", "deficiencies. the first report", "the first report of", "first report of tritan", "report of tritan defects", "of tritan defects was", "tritan defects was in", "defects was in 1952", "in 1952 wright", "1952 wright 1952", "wright 1952 . tritan", "1952 . tritan deficiencies", ". tritan deficiencies are", "tritan deficiencies are inherited", "deficiencies are inherited as", "are inherited as autosomal", "inherited as autosomal dominant", "as autosomal dominant traits", "dominant traits kalmus", "traits kalmus 1955", "kalmus 1955 and", "1955 and are", "and are a result", "are a result of", "a result of missense", "result of missense mutations", "of missense mutations in", "missense mutations in the", "mutations in the blue", "in the blue cone", "the blue cone photopigment", "blue cone photopigment gene", "cone photopigment gene opn1sw", "gene opn1sw leading", "opn1sw leading to", "leading to amino acid", "to amino acid substitutions", "amino acid substitutions in", "acid substitutions in the", "substitutions in the protein", "in the protein sequence.", "the protein sequence. tritan", "protein sequence. tritan defects", "sequence. tritan defects are", "tritan defects are characterized", "defects are characterized by", "are characterized by a", "characterized by a selective", "by a selective deficiency", "a selective deficiency of", "selective deficiency of blue", "deficiency of blue spectral", "of blue spectral sensitivity", "spectral sensitivity weitz", "sensitivity weitz et", "weitz et al. 1992", "et al. 1992 .", "normal human colour vision is", "human colour vision is trichromatic", "vision is trichromatic based", "is trichromatic based on", "trichromatic based on 3", "based on 3 types of", "on 3 types of cones", "3 types of cones that", "types of cones that are", "of cones that are maximally", "cones that are maximally sensitive", "that are maximally sensitive to", "are maximally sensitive to light", "maximally sensitive to light at", "sensitive to light at approximately", "to light at approximately 420", "light at approximately 420 nm", "approximately 420 nm blue", "420 nm blue cones", "blue cones 530", "cones 530 nm", "530 nm green cones", "green cones and", "cones and 560", "and 560 nm red", "560 nm red cones", "nm red cones .", "red cones . neural circuits", "cones . neural circuits compare", ". neural circuits compare light", "neural circuits compare light absorbed", "circuits compare light absorbed by", "compare light absorbed by these", "light absorbed by these 3", "absorbed by these 3 cone", "by these 3 cone types", "these 3 cone types to", "3 cone types to perceive", "cone types to perceive those", "types to perceive those primary", "to perceive those primary colours", "perceive those primary colours and", "those primary colours and combinations", "primary colours and combinations of", "colours and combinations of them.", "and combinations of them. colour", "combinations of them. colour vision", "of them. colour vision deficiencies", "them. colour vision deficiencies result", "colour vision deficiencies result from", "vision deficiencies result from genetic", "deficiencies result from genetic mutations", "result from genetic mutations that", "from genetic mutations that affect", "genetic mutations that affect the", "mutations that affect the expression", "that affect the expression of", "affect the expression of the", "the expression of the full", "expression of the full complement", "of the full complement of", "the full complement of cone", "full complement of cone photoreceptors", "complement of cone photoreceptors and", "of cone photoreceptors and are", "cone photoreceptors and are classified", "photoreceptors and are classified by", "and are classified by severity", "are classified by severity of", "classified by severity of deficiency", "severity of deficiency see", "of deficiency see reviews", "deficiency see reviews deeb", "reviews deeb 2005 simunovic", "deeb 2005 simunovic 2010", "2005 simunovic 2010 .

              tritan", "simunovic 2010 .

              tritan blue", "2010 .

              tritan blue yellow", "blue yellow blue colourblindness", "colourblindness tritanopia mim:190900", "tritanopia mim:190900 deficiencies", "mim:190900 deficiencies are rare", "190900 deficiencies are rare", "deficiencies are rare 1", "are rare 1 in", "rare 1 in 500", "in 500 went", "500 went &", "& pronk 1985 compared", "pronk 1985 compared to", "1985 compared to those", "compared to those involving green", "those involving green and", "involving green and red", "green and red cone", "and red cone deficiencies. the", "red cone deficiencies. the first", "cone deficiencies. the first report", "deficiencies. the first report of", "the first report of tritan", "first report of tritan defects", "report of tritan defects was", "of tritan defects was in", "tritan defects was in 1952", "was in 1952 wright", "in 1952 wright 1952", "1952 wright 1952 .", "wright 1952 . tritan deficiencies", "1952 . tritan deficiencies are", ". tritan deficiencies are inherited", "tritan deficiencies are inherited as", "deficiencies are inherited as autosomal", "are inherited as autosomal dominant", "inherited as autosomal dominant traits", "autosomal dominant traits kalmus", "dominant traits kalmus 1955", "kalmus 1955 and are", "1955 and are a", "and are a result of", "are a result of missense", "a result of missense mutations", "result of missense mutations in", "of missense mutations in the", "missense mutations in the blue", "mutations in the blue cone", "in the blue cone photopigment", "the blue cone photopigment gene", "blue cone photopigment gene opn1sw", "photopigment gene opn1sw leading", "gene opn1sw leading to", "opn1sw leading to amino", "leading to amino acid substitutions", "to amino acid substitutions in", "amino acid substitutions in the", "acid substitutions in the protein", "substitutions in the protein sequence.", "in the protein sequence. tritan", "the protein sequence. tritan defects", "protein sequence. tritan defects are", "sequence. tritan defects are characterized", "tritan defects are characterized by", "defects are characterized by a", "are characterized by a selective", "characterized by a selective deficiency", "by a selective deficiency of", "a selective deficiency of blue", "selective deficiency of blue spectral", "deficiency of blue spectral sensitivity", "blue spectral sensitivity weitz", "spectral sensitivity weitz et", "sensitivity weitz et al.", "weitz et al. 1992 ." ] }, { "record_id": "GLY_000594_1_2182", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9918449", "r hsa", "hsa 9918449", "r hsa 9918449" ] }, { "record_id": "GLY_000594_1_2182", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective visual", "visual phototransduction", "phototransduction due", "due to", "to stra6", "stra6 loss", "loss of", "of function", "defective visual phototransduction", "visual phototransduction due", "phototransduction due to", "due to 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this", "affected by this fatal", "by this fatal syndrome", "this fatal syndrome including", "fatal syndrome including occular", "syndrome including occular and", "including occular and cardiac", "occular and cardiac abnormalities.", "and cardiac abnormalities. microphthalmia", "abnormalities. microphthalmia also", "microphthalmia also called", "called microphthalmos nanophthalmia", "microphthalmos nanophthalmia or", "or nanophthalmos is", "nanophthalmos is a", "is a developmental disorder", "a developmental disorder of", "developmental disorder of the", "disorder of the eye", "of the eye that", "the eye that literally", "eye that literally means", "that literally means small", "literally means small eye", "means small eye and", "small eye and in", "eye and in most", "and in most cases", "in most cases results", "most cases results in", "cases results in blindness.", "defects in stra6 cause microphthalmia", "in stra6 cause microphthalmia syndromic", "stra6 cause microphthalmia syndromic type", "cause microphthalmia syndromic type 9", "syndromic type 9 mcops9", "9 mcops9 matthew", "mcops9 matthew wood syndrome", "matthew wood syndrome or spear", "wood syndrome or spear syndrome", "or spear syndrome mim:601186", "mim:601186 chassaing et", "601186 chassaing et", "chassaing et al. 2009 .", "et al. 2009 . mutiple", "al. 2009 . mutiple systems", "2009 . mutiple systems are", ". mutiple systems are affected", "mutiple systems are affected by", "systems are affected by this", "are affected by this fatal", "affected by this fatal syndrome", "by this fatal syndrome including", "this fatal syndrome including occular", "fatal syndrome including occular and", "syndrome including occular and cardiac", "including occular and cardiac abnormalities.", "occular and cardiac abnormalities. microphthalmia", "cardiac abnormalities. microphthalmia also", "abnormalities. microphthalmia also called", "microphthalmia also called microphthalmos", "also called microphthalmos nanophthalmia", "called microphthalmos nanophthalmia or", "microphthalmos nanophthalmia or nanophthalmos", "nanophthalmia or nanophthalmos is", "or nanophthalmos is a", "nanophthalmos is a developmental", "is a developmental disorder of", "a developmental disorder of the", "developmental disorder of the eye", "disorder of the eye that", "of the eye that literally", "the eye that literally means", "eye that literally means small", "that literally means small eye", "literally means small eye and", "means small eye and in", "small eye and in most", "eye and in most cases", "and in most cases results", "in most cases results in", "most cases results in blindness." ] }, { "record_id": "GLY_000594_1_2183", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9918450", "r hsa", "hsa 9918450", "r hsa 9918450" ] }, { "record_id": "GLY_000594_1_2183", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "defective visual", "visual phototransduction", "phototransduction due", "due to", "to opn1lw", "opn1lw loss", "loss of", "of function", "defective visual phototransduction", "visual phototransduction due", "phototransduction due to", "due to opn1lw", "to opn1lw loss", "opn1lw loss of", "loss of function", "defective visual phototransduction due", "visual phototransduction due to", "phototransduction due to opn1lw", "due to opn1lw loss", "to opn1lw loss of", "opn1lw loss of function", "defective visual phototransduction due to", "visual phototransduction due to opn1lw", "phototransduction due to opn1lw loss", "due to opn1lw loss of", "to opn1lw loss of function", "blue cone", "cone monochromatism", "is a", "a rare", "rare x", "x linked", "linked congenital", "congenital cone", "cone dysfunction", "dysfunction characterized", "characterized by", "by the", "the absence", "absence of", "of functional", "functional long", "long wavelength", "wavelength sensitive", "and medium", "medium wavelength", "cones in", "in the", "the retina.", "retina. colour", "colour discrimination", "discrimination is", "is severely", "severely impaired", "impaired from", "from birth", "and vision", "vision is", "is derived", "derived from", "from the", "the preserved", "preserved short", "short wavelength", "cones and", "and rod", "rod photoreceptors.", "photoreceptors. bcm", "bcm typically", "typically presents", "presents with", "with reduced", "reduced visual", "visual acuity", "pendular nystagmus", "photophobia and", "and patients", "patients often", "often have", "have myopia.", "myopia. bcm", "bcm affects", "affects approximately", "approximately 1", "1 in", "in 100", "100 000", "000 individuals", "individuals and", "and can", "can be", "be caused", "caused by", "by loss", "function mutations", "mutations in", "the opn1lw", "opn1lw gene", "see review", "review gardner", "gardner et", "et al.", "al. 2009", "2009 .

              defects", ".

              defects in", "in opn1lw", "opn1lw also", "also cause", "cause partial", "partial colorblindness", "protan series", "to non", "non functional", "functional red", "red cones", "ueyama et", "al. 2002", "2002 .", "blue cone monochromatism", "monochromatism bcm", "bcm is", "is a rare", "a rare x", "rare x linked", "x linked congenital", "linked congenital cone", "congenital cone dysfunction", "cone dysfunction characterized", "dysfunction characterized by", "characterized by the", "by the absence", "the absence of", "absence of functional", "of functional long", "functional long wavelength", "long wavelength sensitive", "sensitive red", "red and", "and medium wavelength", "medium wavelength sensitive", "sensitive green", "green cones", "cones in the", "in the retina.", "the retina. colour", "retina. colour discrimination", "colour discrimination is", "discrimination is severely", "is severely impaired", "severely impaired from", "impaired from birth", "birth and", "and vision is", "vision is derived", "is derived from", "derived from the", "from the preserved", "the preserved short", "preserved short wavelength", "short wavelength sensitive", "sensitive blue", "blue cones", "cones and rod", "and rod photoreceptors.", "rod photoreceptors. bcm", "photoreceptors. bcm typically", "bcm typically presents", "typically presents with", "presents with reduced", "with reduced visual", "reduced visual acuity", "acuity pendular", "nystagmus photophobia", "photophobia and patients", "and patients often", "patients often have", "often have myopia.", "have myopia. bcm", "myopia. bcm affects", "bcm affects approximately", "affects approximately 1", "approximately 1 in", "1 in 100", "in 100 000", "100 000 individuals", "000 individuals and", "individuals and can", "and can be", "can be caused", "be caused by", "caused by loss", "by loss of", "of function mutations", "function mutations in", "mutations in the", "in the opn1lw", "the opn1lw gene", "gene see", "see review gardner", "review gardner et", "gardner et al.", "et al. 2009", "al. 2009 .

              defects", "2009 .

              defects in", ".

              defects in opn1lw", "in opn1lw also", "opn1lw also cause", "also cause partial", "cause partial colorblindness", "colorblindness protan", "series cbp", "cbp protanopia", "protanopia mim:303900", "mim:303900 due", "303900 due", "due to non", "to non functional", "non functional red", "functional red cones", "cones ueyama", "ueyama et al.", "et al. 2002", "al. 2002 .", "cone monochromatism bcm", "bcm is a", "is a rare x", "a rare x linked", "rare x linked congenital", "x linked congenital cone", "linked congenital cone dysfunction", "congenital cone dysfunction characterized", "cone dysfunction characterized by", "dysfunction characterized by the", "characterized by the absence", "by the absence of", "the absence of functional", "absence of functional long", "of functional long wavelength", "functional long wavelength sensitive", "wavelength sensitive red", "red and medium", "and medium wavelength sensitive", "wavelength sensitive green", "green cones in", "cones in the retina.", "in the retina. colour", "the retina. colour discrimination", "retina. colour discrimination is", "colour discrimination is severely", "discrimination is severely impaired", "is severely impaired from", "severely impaired from birth", "from birth and", "birth and vision", "and vision is derived", "vision is derived from", "is derived from the", "derived from the preserved", "from the preserved short", "the preserved short wavelength", "preserved short wavelength sensitive", "wavelength sensitive blue", "blue cones and", "cones and rod photoreceptors.", "and rod photoreceptors. bcm", "rod photoreceptors. bcm typically", "photoreceptors. bcm typically presents", "bcm typically presents with", "typically presents with reduced", "presents with reduced visual", "with reduced visual acuity", "visual acuity pendular", "acuity pendular nystagmus", "pendular nystagmus photophobia", "nystagmus photophobia and", "photophobia and patients often", "and patients often have", "patients often have myopia.", "often have myopia. bcm", "have myopia. bcm affects", "myopia. bcm affects approximately", "bcm affects approximately 1", "affects approximately 1 in", "approximately 1 in 100", "1 in 100 000", "in 100 000 individuals", "100 000 individuals and", "000 individuals and can", "individuals and can be", "and can be caused", "can be caused by", "be caused by loss", "caused by loss of", "by loss of function", "loss of function mutations", "of function mutations in", "function mutations in the", "mutations in the opn1lw", "in the opn1lw gene", "opn1lw gene see", "gene see review", "see review gardner et", "review gardner et al.", "gardner et al. 2009", "et al. 2009 .

              defects", "al. 2009 .

              defects in", "2009 .

              defects in opn1lw", ".

              defects in opn1lw also", "in opn1lw also cause", "opn1lw also cause partial", "also cause partial colorblindness", "partial colorblindness protan", "colorblindness protan series", "protan series cbp", "mim:303900 due to", "303900 due to", "due to non functional", "to non functional red", "non functional red cones", "red cones ueyama", "cones ueyama et", "ueyama et al. 2002", "et al. 2002 .", "blue cone monochromatism bcm", "monochromatism bcm is", "bcm is a rare", "is a rare x linked", "a rare x linked congenital", "rare x linked congenital cone", "x linked congenital cone dysfunction", "linked congenital cone dysfunction characterized", "congenital cone dysfunction characterized by", "cone dysfunction characterized by the", "dysfunction characterized by the absence", "characterized by the absence of", "by the absence of functional", "the absence of functional long", "absence of functional long wavelength", "of functional long wavelength sensitive", "long wavelength sensitive red", "sensitive red and", "red and medium wavelength", "medium wavelength sensitive green", "sensitive green cones", "green cones in the", "cones in the retina. colour", "in the retina. colour discrimination", "the retina. colour discrimination is", "retina. colour discrimination is severely", "colour discrimination is severely impaired", "discrimination is severely impaired from", "is severely impaired from birth", "impaired from birth and", "from birth and vision", "birth and vision is", "and vision is derived from", "vision is derived from the", "is derived from the preserved", "derived from the preserved short", "from the preserved short wavelength", "the preserved short wavelength sensitive", "short wavelength sensitive blue", "sensitive blue cones", "blue cones and rod", "cones and rod photoreceptors. bcm", "and rod photoreceptors. bcm typically", "rod photoreceptors. bcm typically presents", "photoreceptors. bcm typically presents with", "bcm typically presents with reduced", "typically presents with reduced visual", "presents with reduced visual acuity", "reduced visual acuity pendular", "visual acuity pendular nystagmus", "pendular nystagmus photophobia and", "nystagmus photophobia and patients", "photophobia and patients often have", "and patients often have myopia.", "patients often have myopia. bcm", "often have myopia. bcm affects", "have myopia. bcm affects approximately", "myopia. bcm affects approximately 1", "bcm affects approximately 1 in", "affects approximately 1 in 100", "approximately 1 in 100 000", "1 in 100 000 individuals", "in 100 000 individuals and", "100 000 individuals and can", "000 individuals and can be", "individuals and can be caused", "and can be caused by", "can be caused by loss", "be caused by loss of", "caused by loss of function", "by loss of function mutations", "loss of function mutations in", "of function mutations in the", "function mutations in the opn1lw", "mutations in the opn1lw gene", "the opn1lw gene see", "opn1lw gene see review", "gene see review gardner", "see review gardner et al.", "review gardner et al. 2009", "gardner et al. 2009 .

              defects", "et al. 2009 .

              defects in", "al. 2009 .

              defects in opn1lw", "2009 .

              defects in opn1lw also", ".

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              mutations in", ".

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              mutations", "2023 .

              mutations in any", ".

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              mutations", "al. 2023 .

              mutations in", "2023 .

              mutations in any complex", ".

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infections", "viral infections dediego", "infections dediego ml", "dediego ml et al.", "et al. 2019a", "b villamayor l", "villamayor l l\u00f3pez", "l l\u00f3pez garc\u00eda", "l\u00f3pez garc\u00eda d et", "garc\u00eda d et al.", "et al. 2023", "2023 villamayor l", "villamayor l rivero", "l rivero v", "rivero v et al.", "al. 2023 .", "excessive or long lasting innate", "or long lasting innate immune", "long lasting innate immune responses", "lasting innate immune responses can", "innate immune responses can be", "immune responses can be harmful", "responses can be harmful to", "can be harmful to the", "be harmful to the host", "to the host so", "the host so negative", "host so negative feedback", "so negative feedback mechanisms are", "negative feedback mechanisms are essential.", "feedback mechanisms are essential. this", "mechanisms are essential. this reactome", "are essential. this reactome pathway", "essential. this reactome pathway describes", "this reactome pathway describes regulatory", "reactome pathway describes regulatory functions", "pathway describes regulatory functions of", "describes regulatory functions of selected", "regulatory functions of selected interferon", "of selected interferon ifn", "interferon ifn stimulated", "genes isgs such", "isgs such as ifi44", "such as ifi44 ifi44l", "ifi44 ifi44l ifi6", "ifi44l ifi6 and ifi27", "ifi6 and ifi27 that suppress", "and ifi27 that suppress the", "ifi27 that suppress the ifn", "that suppress the ifn mediated", "suppress the ifn mediated innate", "the ifn mediated innate immune", "ifn mediated innate immune responses", "mediated innate immune responses triggered", "innate immune responses triggered by", "immune responses triggered by viral", "responses triggered by viral infections", "by viral infections dediego", "viral infections dediego ml", "infections dediego ml et", "ml et al. 2019a", "al. 2019a b", "2019a b villamayor", "villamayor l l\u00f3pez garc\u00eda", "l l\u00f3pez garc\u00eda d", "l\u00f3pez garc\u00eda d et al.", "d et al. 2023", "al. 2023 villamayor", "villamayor l rivero v", "l rivero v et", "v et al. 2023", "et al. 2023 ." ] }, { "record_id": "GLY_000594_1_2190", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9912633", "r hsa", "hsa 9912633", "r hsa 9912633" ] }, { "record_id": "GLY_000594_1_2190", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "antigen processing:", "processing: ub", "atp independent", "independent proteasomal", "proteasomal degradation", "antigen processing: ub", "ub atp", "atp independent proteasomal", "independent proteasomal degradation", "processing: ub atp", "ub atp independent", "atp independent proteasomal degradation", "antigen processing: ub atp", "processing: ub atp independent", "ub atp independent proteasomal", "intracellular foreign", "foreign or", "or aberrant", "aberrant host", "host proteins", "proteins are", "are cleaved", "cleaved into", "into peptide", "peptide fragments", "fragments of", "of a", "a precise", "precise size", "such that", "that they", "they can", "can be", "be loaded", "loaded on", "on to", "to class", "class i", "i major", "major histocompatibility", "histocompatibility complex", "mhc i", "molecules and", "and presented", "presented externally", "externally to", "to cytotoxic", "cytotoxic cd8+", "cd8+ t", "t lymphocytes", "reviewed by", "by embgenbroich", "embgenbroich m", "m &", "& burgdorf", "burgdorf s", "s 2018", "2018 .", ". in", "in the", "the cytosol", "ctl recognized", "recognized peptides", "peptides are", "are generated", "generated by", "by proteasomes", "which exist", "exist as", "as a", "a mixture", "mixture of", "of compositionally", "compositionally distinct", "distinct complexes", "by kloetzel", "kloetzel pm", "pm 2004", "habib ja", "ja et", "et al.", "2022 .", ". the", "the proteasome", "proteasome complex", "complex consists", "consists of", "of 20s", "20s proteolytic", "proteolytic core", "core particle", "associated with", "with a", "a regulatory", "regulatory particle", "such as", "as 19s", "19s rp", "rp or", "or pa28", "pa28 rp", "zhao j", "j et", "al. 2022", "adolf f", "f et", "by watanabe", "watanabe a", "a et", "the catalytic", "catalytic subunits", "subunits psmb6", "and psmb5", "within 20s", "20s cp", "cp exhibit", "exhibit caspase", "caspase like", "trypsin like", "and chymotrypsin", "chymotrypsin like", "like activities", "vigneron n", "n et", "al. 2015", "rut w", "w &", "& drag", "drag m", "m 2016", "2016 .", ". during", "during peptide", "peptide bond", "bond cleavage", "threonine from", "from the", "the active", "active site", "site of", "of the", "catalytic \u03b2", "\u03b2 subunit", "subunit binds", "binds to", "to the", "the n", "n terminal", "terminal peptide", "peptide fragment", "fragment forming", "forming an", "an unstable", "unstable acyl", "acyl enzyme", "enzyme intermediate", "where a", "a peptide", "fragment remains", "remains attached", "attached to", "the proteasome.", "proteasome. subsequently", "a water", "water molecule", "molecule hydrolyzes", "hydrolyzes the", "the bond", "bond between", "between the", "the peptide", "peptide and", "and the", "resulting in", "the release", "release of", "the peptide's", "peptide's c", "c terminal", "terminal end", "mishto m", "m et", "al. 2012", "ebstein f", "al. 2016", "soh wt", "wt et", "2024 .", ". either", "either one", "one or", "or two", "two regulatory", "regulatory particles", "can attach", "attach to", "the 20s", "the 19s", "rp binds", "binds 20s", "cp to", "to form", "form the", "the 26s", "26s proteasome", "which degrades", "degrades both", "both foreign", "foreign and", "and self", "self proteins", "proteins in", "the ubiquitin", "and atp", "atp dependent", "dependent manner", "zhu y", "y et", "dong y", "zhang s", "s et", "by sahu", "sahu i", "i &", "& glickman", "glickman mh", "mh 2021a", "2021a .", "in addition", "a subset", "subset of", "of intracellular", "intracellular proteins", "especially intrinsically", "intrinsically disordered", "disordered proteins", "can directly", "directly bind", "bind to", "to 20s", "cp for", "for ub", "makaros y", "mamrosh jl", "jl et", "pepelnjak m", "mh 2021", "2021 b", "bialek w", "w et", "2023 .", ". unlike", "unlike 19s", "the pa28", "pa28 regulatory", "particle does", "does not", "not have", "have a", "a ubiquitin", "ubiquitin receptor", "binding of", "of pa28", "pa28 to", "cp promotes", "promotes ub", "independent protein", "protein breakdown.", "breakdown. pa28", "pa28 proteasomes", "proteasomes are", "are thought", "thought to", "to be", "be important", "important for", "for rapid", "rapid degradation", "degradation of", "of misfolded", "misfolded proteins", "proteins under", "under conditions", "conditions of", "of oxidative", "oxidative stress", "stress or", "or degradation", "of proteins", "proteins with", "with intrinsically", "disordered regions", "chen j", "by thomas", "thomas t", "t et", "al. 2023", ". various", "various immune", "immune cells", "as t", "t cells", "b cells", "and antigen", "antigen presenting", "presenting cells", "constitutively express", "express a", "a specialized", "specialized form", "form of", "of proteasomes", "known as", "as immunoproteasomes", "in which", "which the", "cp are", "are substituted", "substituted with", "with psmb9", "and psmb8", "shin ec", "ec et", "bai m", "santos r", "r et", "2017 .", ". this", "this variation", "variation of", "the core", "particle is", "is known", "as 20s", "20s icp.", "icp. immunoproteasomes", "immunoproteasomes utilize", "utilize the", "particle to", "to degrade", "degrade antigens", "lesne j", "2021 .", ". under", "under inflammatory", "inflammatory conditions", "the expression", "expression of", "catalytic and", "and pa28", "regulatory subunits", "subunits of", "of immunoproteasome", "immunoproteasome is", "is induced", "induced by", "by cytokines", "cytokines like", "like interferon", "interferon gamma", "type i", "i interferons", "and tumor", "tumor necrosis", "necrosis factor", "factor alpha", "tnf \u03b1", "\u03b1 .", ". immunoproteasomes", "immunoproteasomes possess", "possess enhanced", "enhanced chymotrypsin", "and trypsin", "alongside with", "with the", "the reduced", "reduced caspase", "like activity.", "activity. these", "these distinct", "distinct enzymatic", "enzymatic properties", "properties of", "of immunoproteasomes", "immunoproteasomes generate", "generate substrate", "substrate cleavage", "cleavage patterns", "patterns that", "that enhance", "enhance loading", "loading of", "of peptides", "peptides onto", "onto the", "the class", "i mhc", "mhc for", "for immune", "immune presentation", "presentation to", "to ctl", "by tomko", "tomko rj", "rj and", "and hochstrasser", "hochstrasser m", "m 2013", "2013 .

              this", ".

              this reactome", "reactome module", "module describes", "describes ub", "ub independent", "independent antigen", "antigen processing", "processing by", "by pa28", "pa28 20s", "cp and", "20s icp", "icp proteasomes.", "intracellular foreign or", "foreign or aberrant", "or aberrant host", "aberrant host proteins", "host proteins are", "proteins are cleaved", "are cleaved into", "cleaved into peptide", "into peptide fragments", "peptide fragments of", "fragments of a", "of a precise", "a precise size", "size such", "such that they", "that they can", "they can be", "can be loaded", "be loaded on", "loaded on to", "on to class", "to class i", "class i major", "i major histocompatibility", "major histocompatibility complex", "complex mhc", "i molecules", "molecules and presented", "and presented externally", "presented externally to", "externally to cytotoxic", "to cytotoxic cd8+", "cytotoxic cd8+ t", "cd8+ t lymphocytes", "lymphocytes ctls", "reviewed by embgenbroich", "by embgenbroich m", "embgenbroich m &", "m & burgdorf", "& burgdorf s", "burgdorf s 2018", "s 2018 .", "2018 . in", ". in the", "in the cytosol", "cytosol ctl", "ctl recognized peptides", "recognized peptides are", "peptides are generated", "are generated by", "generated by proteasomes", "proteasomes which", "which exist as", "exist as a", "as a mixture", "a mixture of", "mixture of compositionally", "of compositionally distinct", "compositionally distinct complexes", "complexes reviewed", "reviewed by kloetzel", "by kloetzel pm", "kloetzel pm 2004", "2004 habib", "habib ja et", "ja et al.", "2022 . the", ". the proteasome", "the proteasome complex", "proteasome complex consists", "complex consists of", "consists of 20s", "of 20s proteolytic", "20s proteolytic core", "proteolytic core particle", "particle cp", "cp associated", "associated with a", "with a regulatory", "a regulatory particle", "particle rp", "rp such", "such as 19s", "as 19s rp", "19s rp or", "rp or pa28", "or pa28 rp", "rp zhao", "zhao j et", "j et al.", "et al. 2022", "2022 adolf", "adolf f et", "f et al.", "al. 2024", "2024 reviewed", "reviewed by watanabe", "by watanabe a", "watanabe a et", "a et al.", ". the catalytic", "the catalytic subunits", "catalytic subunits psmb6", "psmb6 \u03b21", "psmb7 \u03b22", "psmb5 \u03b25", "\u03b25 within", "within 20s cp", "20s cp exhibit", "cp exhibit caspase", "exhibit caspase like", "like trypsin", "like and", "and chymotrypsin like", "chymotrypsin like activities", "activities respectively", "respectively vigneron", "vigneron n et", "n et al.", "et al. 2015", "2015 rut", "rut w &", "w & drag", "& drag m", "drag m 2016", "m 2016 .", "2016 . during", ". during peptide", "during peptide bond", "peptide bond cleavage", "cleavage threonine", "threonine from the", "from the active", "the active site", "active site of", "site of the", "of the catalytic", "the catalytic \u03b2", "catalytic \u03b2 subunit", "\u03b2 subunit binds", "subunit binds to", "binds to the", "to the n", "the n terminal", "n terminal peptide", "terminal peptide fragment", "peptide fragment forming", "fragment forming an", "forming an unstable", "an unstable acyl", "unstable acyl enzyme", "acyl enzyme intermediate", "intermediate where", "where a peptide", "a peptide fragment", "peptide fragment remains", "fragment remains attached", "remains attached to", "attached to the", "to the proteasome.", "the proteasome. subsequently", "subsequently a", "a water molecule", "water molecule hydrolyzes", "molecule hydrolyzes the", "hydrolyzes the bond", "the bond between", "bond between the", "between the peptide", "the peptide and", "peptide and the", "and the proteasome", "proteasome resulting", "resulting in the", "in the release", "the release of", "release of the", "of the peptide's", "the peptide's c", "peptide's c terminal", "c terminal end", "end mishto", "mishto m et", "m et al.", "et al. 2012", "2012 ebstein", "ebstein f et", "et al. 2016", "2016 soh", "soh wt et", "wt et al.", "2024 . either", ". either one", "either one or", "one or two", "or two regulatory", "two regulatory particles", "particles rp", "rp can", "can attach to", "attach to the", "to the 20s", "the 20s cp", "cp zhao", ". the 19s", "the 19s rp", "19s rp binds", "rp binds 20s", "binds 20s cp", "20s cp to", "cp to form", "to form the", "form the 26s", "the 26s proteasome", "proteasome which", "which degrades both", "degrades both foreign", "both foreign and", "foreign and self", "and self proteins", "self proteins in", "proteins in the", "in the ubiquitin", "ubiquitin ub", "and atp dependent", "atp dependent manner", "manner zhu", "zhu y et", "y et al.", "al. 2018", "2018 dong", "dong y et", "al. 2019", "2019 zhang", "zhang s et", "s et al.", "2022 reviewed", "reviewed by sahu", "by sahu i", "sahu i &", "i & glickman", "& glickman mh", "glickman mh 2021a", "mh 2021a .", "2021a . in", ". in addition", "addition a", "a subset of", "subset of intracellular", "of intracellular proteins", "proteins especially", "especially intrinsically disordered", "intrinsically disordered proteins", "proteins can", "can directly bind", "directly bind to", "bind to 20s", "to 20s cp", "20s cp for", "cp for ub", "ub and", "and atp independent", "degradation makaros", "makaros y et", "2023 mamrosh", "mamrosh jl et", "jl et al.", "2023 pepelnjak", "pepelnjak m et", "glickman mh 2021", "mh 2021 b", "b bialek", "bialek w et", "w et al.", "2023 . unlike", ". unlike 19s", "19s the", "the pa28 regulatory", "pa28 regulatory particle", "regulatory particle does", "particle does not", "does not have", "not have a", "have a ubiquitin", "a ubiquitin receptor", "receptor binding", "binding of pa28", "of pa28 to", "pa28 to the", "20s cp promotes", "cp promotes ub", "atp independent protein", "independent protein breakdown.", "protein breakdown. pa28", "breakdown. pa28 proteasomes", "pa28 proteasomes are", "proteasomes are thought", "are thought to", "thought to be", "to be important", "be important for", "important for rapid", "for rapid degradation", "rapid degradation of", "degradation of misfolded", "of misfolded proteins", "misfolded proteins under", "proteins under conditions", "under conditions of", "conditions of oxidative", "of oxidative stress", "oxidative stress or", "stress or degradation", "or degradation of", "degradation of proteins", "of proteins with", "proteins with intrinsically", "with intrinsically disordered", "intrinsically disordered regions", "regions habib", "al. 2020", "2020 chen", "chen j et", "al. 2021", "2021 zhao", "reviewed by thomas", "by thomas t", "thomas t et", "t et al.", "et al. 2023", "al. 2023 .", "2023 . various", ". various immune", "various immune cells", "cells such", "such as t", "as t cells", "cells b", "cells and", "and antigen presenting", "antigen presenting cells", "cells constitutively", "constitutively express a", "express a specialized", "a specialized form", "specialized form of", "form of proteasomes", "proteasomes known", "known as immunoproteasomes", "immunoproteasomes in", "in which the", "which the catalytic", "\u03b25 of", "of 20s cp", "20s cp are", "cp are substituted", "are substituted with", "substituted with psmb9", "psmb9 \u03b21i", "psmb10 \u03b22i", "psmb8 \u03b25i", "respectively shin", "shin ec et", "ec et al.", "al. 2006", "2006 bai", "bai m et", "al. 2014", "2014 santos", "santos r et", "r et al.", "al. 2017", "2017 . this", ". this variation", "this variation of", "variation of the", "of the core", "the core particle", "core particle is", "particle is known", "is known as", "known as 20s", "as 20s icp.", "20s icp. immunoproteasomes", "icp. immunoproteasomes utilize", "immunoproteasomes utilize the", "utilize the pa28", "regulatory particle to", "particle to degrade", "to degrade antigens", "antigens lesne", "lesne j et", "2021 . under", ". under inflammatory", "under inflammatory conditions", "conditions the", "the expression of", "expression of the", "the catalytic and", "catalytic and pa28", "and pa28 regulatory", "pa28 regulatory subunits", "regulatory subunits of", "subunits of immunoproteasome", "of immunoproteasome is", "immunoproteasome is induced", "is induced by", "induced by cytokines", "by cytokines like", "cytokines like interferon", "like interferon gamma", "gamma ifn\u03b3", "type i interferons", "interferons and", "and tumor necrosis", "tumor necrosis factor", "necrosis factor alpha", "alpha tnf", "tnf \u03b1 .", "\u03b1 . immunoproteasomes", ". immunoproteasomes possess", "immunoproteasomes possess enhanced", "possess enhanced chymotrypsin", "chymotrypsin and", "and trypsin like", "trypsin like activities", "activities alongside", "alongside with the", "with the reduced", "the reduced caspase", "reduced caspase like", "caspase like activity.", "like activity. these", "activity. these distinct", "these distinct enzymatic", "distinct enzymatic properties", "enzymatic properties of", "properties of immunoproteasomes", "of immunoproteasomes generate", "immunoproteasomes generate substrate", "generate substrate cleavage", "substrate cleavage patterns", "cleavage patterns that", "patterns that enhance", "that enhance loading", "enhance loading of", "loading of peptides", "of peptides onto", "peptides onto the", "onto the class", "the class i", "class i mhc", "i mhc for", "mhc for immune", "for immune presentation", "immune presentation to", "presentation to ctl", "ctl reviewed", "reviewed by tomko", "by tomko rj", "tomko rj and", "rj and hochstrasser", "and hochstrasser m", "hochstrasser m 2013", "m 2013 .

              this", "2013 .

              this reactome", ".

              this reactome module", "reactome module describes", "module describes ub", "describes ub independent", "ub independent antigen", "independent antigen processing", "antigen processing by", "processing by pa28", "by pa28 20s", "pa28 20s cp", "20s cp and", "cp and pa28", "and pa28 20s", "pa28 20s icp", "20s icp proteasomes.", "intracellular foreign or aberrant", "foreign or aberrant host", "or aberrant host proteins", "aberrant host proteins are", "host proteins are cleaved", "proteins are cleaved into", "are cleaved into peptide", "cleaved into peptide fragments", "into peptide fragments of", "peptide fragments of a", "fragments of a precise", "of a precise size", "precise size such", "size such that", "such that they can", "that they can be", "they can be loaded", "can be loaded on", "be loaded on to", "loaded on to class", "on to class i", "to class i major", "class i major histocompatibility", "i major histocompatibility complex", "histocompatibility complex mhc", "complex mhc i", "mhc i molecules", "i molecules and", "molecules and presented externally", "and presented externally to", "presented externally to cytotoxic", "externally to cytotoxic cd8+", "to cytotoxic cd8+ t", "cytotoxic cd8+ t lymphocytes", "t lymphocytes ctls", "ctls reviewed", "reviewed by embgenbroich m", "by embgenbroich m &", "embgenbroich m & burgdorf", "m & burgdorf s", "& burgdorf s 2018", "burgdorf s 2018 .", "s 2018 . in", "2018 . in the", ". in the cytosol", "the cytosol ctl", "cytosol ctl recognized", "ctl recognized peptides are", "recognized peptides are generated", "peptides are generated by", "are generated by proteasomes", "by proteasomes which", "proteasomes which exist", "which exist as a", "exist as a mixture", "as a mixture of", "a mixture of compositionally", "mixture of compositionally distinct", "of compositionally distinct complexes", "distinct complexes reviewed", "complexes reviewed by", "reviewed by kloetzel pm", "by kloetzel pm 2004", "pm 2004 habib", "2004 habib ja", "habib ja et al.", "al. 2022 .", "2022 . the proteasome", ". the proteasome complex", "the proteasome complex consists", "proteasome complex consists of", "complex consists of 20s", "consists of 20s proteolytic", "of 20s proteolytic core", "20s proteolytic core particle", "core particle cp", "cp associated with", "associated with a regulatory", "with a regulatory particle", "regulatory particle rp", "rp such as", "such as 19s rp", "as 19s rp or", "19s rp or pa28", "rp or pa28 rp", "pa28 rp zhao", "rp zhao j", "zhao j et al.", "j et al. 2022", "al. 2022 adolf", "2022 adolf f", "adolf f et al.", "et al. 2024", "2024 reviewed by", "reviewed by watanabe a", "by watanabe a et", "watanabe a et al.", "2022 . the catalytic", ". the catalytic subunits", "the catalytic subunits psmb6", "subunits psmb6 \u03b21", "\u03b21 psmb7", "\u03b22 and", "and psmb5 \u03b25", "\u03b25 within 20s", "within 20s cp exhibit", "20s cp exhibit caspase", "cp exhibit caspase like", "caspase like trypsin", "like trypsin like", "trypsin like and", "like and chymotrypsin", "and chymotrypsin like activities", "like activities respectively", "respectively vigneron n", "vigneron n et al.", "n et al. 2015", "al. 2015 rut", "2015 rut w", "rut w & drag", "w & drag m", "& drag m 2016", "drag m 2016 .", "m 2016 . during", "2016 . during peptide", ". during peptide bond", "during peptide bond cleavage", "bond cleavage threonine", "cleavage threonine from", "threonine from the active", "from the active site", "the active site of", "active site of the", "site of the catalytic", "of the catalytic \u03b2", "the catalytic \u03b2 subunit", "catalytic \u03b2 subunit binds", "\u03b2 subunit binds to", "subunit binds to the", "binds to the n", "to the n terminal", "the n terminal peptide", "n terminal peptide fragment", "terminal peptide fragment forming", "peptide fragment forming an", "fragment forming an unstable", "forming an unstable acyl", "an unstable acyl enzyme", "unstable acyl enzyme intermediate", "enzyme intermediate where", "intermediate where a", "where a peptide fragment", "a peptide fragment remains", "peptide fragment remains attached", "fragment remains attached to", "remains attached to the", "attached to the proteasome.", "to the proteasome. subsequently", "proteasome. subsequently a", "subsequently a water", "a water molecule hydrolyzes", "water molecule hydrolyzes the", "molecule hydrolyzes the bond", "hydrolyzes the bond between", "the bond between the", "bond between the peptide", "between the peptide and", "the peptide and the", "peptide and the proteasome", "the proteasome resulting", "proteasome resulting in", "resulting in the release", "in the release of", "the release of the", "release of the peptide's", "of the peptide's c", "the peptide's c terminal", "peptide's c terminal end", "terminal end mishto", "end mishto m", "mishto m et al.", "m et al. 2012", "al. 2012 ebstein", "2012 ebstein f", "ebstein f et al.", "f et al. 2016", "al. 2016 soh", "2016 soh wt", "soh wt et al.", "al. 2024 .", "2024 . either one", ". either one or", "either one or two", "one or two regulatory", "or two regulatory particles", "regulatory particles rp", "rp can attach", "can attach to the", "attach to the 20s", "to the 20s cp", "20s cp zhao", "cp zhao j", "2022 . the 19s", ". the 19s rp", "the 19s rp binds", "19s rp binds 20s", "rp binds 20s cp", "binds 20s cp to", "20s cp to form", "cp to form the", "to form the 26s", "form the 26s proteasome", "26s proteasome which", "proteasome which degrades", "which degrades both foreign", "degrades both foreign and", "both foreign and self", "foreign and self proteins", "and self proteins in", "self proteins in the", "proteins in the ubiquitin", "the ubiquitin ub", "and atp dependent manner", "dependent manner zhu", "manner zhu y", "zhu y et al.", "et al. 2018", "2018 dong y", "dong y et al.", "et al. 2019", "2019 zhang s", "zhang s et al.", "2022 reviewed by", "reviewed by sahu i", "by sahu i &", "sahu i & glickman", "i & glickman mh", "& glickman mh 2021a", "glickman mh 2021a .", "mh 2021a . in", "2021a . in addition", "in addition a", "addition a subset", "a subset of intracellular", "subset of intracellular proteins", "intracellular proteins especially", "proteins especially intrinsically", "especially intrinsically disordered proteins", "disordered proteins can", "proteins can directly", "can directly bind to", "directly bind to 20s", "bind to 20s cp", "to 20s cp for", "20s cp for ub", "for ub and", "ub and atp", "and atp independent proteasomal", "proteasomal degradation makaros", "degradation makaros y", "makaros y et al.", "2023 mamrosh jl", "mamrosh jl et al.", "2023 pepelnjak m", "pepelnjak m et al.", "& glickman mh 2021", "glickman mh 2021 b", "2021 b bialek", "b bialek w", "bialek w et al.", "2023 . unlike 19s", "unlike 19s the", "19s the pa28", "the pa28 regulatory particle", "pa28 regulatory particle does", "regulatory particle does not", "particle does not have", "does not have a", "not have a ubiquitin", "have a ubiquitin receptor", "ubiquitin receptor binding", "receptor binding of", "binding of pa28 to", "of pa28 to the", "pa28 to the 20s", "the 20s cp promotes", "20s cp promotes ub", "atp independent protein breakdown.", "independent protein breakdown. pa28", "protein breakdown. pa28 proteasomes", "breakdown. pa28 proteasomes are", "pa28 proteasomes are thought", "proteasomes are thought to", "are thought to be", "thought to be important", "to be important for", "be important for rapid", "important for rapid degradation", "for rapid degradation of", "rapid degradation of misfolded", "degradation of misfolded proteins", "of misfolded proteins under", "misfolded proteins under conditions", "proteins under conditions of", "under conditions of oxidative", "conditions of oxidative stress", "of oxidative stress or", "oxidative stress or degradation", "stress or degradation of", "or degradation of proteins", "degradation of proteins with", "of proteins with intrinsically", "proteins with intrinsically disordered", "with intrinsically disordered regions", "disordered regions habib", "regions habib ja", "et al. 2020", "2020 chen j", "chen j et al.", "et al. 2021", "2021 zhao j", "al. 2022 reviewed", "reviewed by thomas t", "by thomas t et", "thomas t et al.", "t et al. 2023", "et al. 2023 .", "al. 2023 . various", "2023 . various immune", ". various immune cells", "immune cells such", "cells such as", "such as t cells", "t cells b", "cells b cells", "b cells and", "cells and antigen", "and antigen presenting cells", "presenting cells constitutively", "cells constitutively express", "constitutively express a specialized", "express a specialized form", "a specialized form of", "specialized form of proteasomes", "of proteasomes known", "proteasomes known as", "as immunoproteasomes in", "immunoproteasomes in which", "in which the catalytic", "which the catalytic subunits", "\u03b25 of 20s", "of 20s cp are", "20s cp are substituted", "cp are substituted with", "are substituted with psmb9", "with psmb9 \u03b21i", "\u03b21i psmb10", "\u03b22i and", "and psmb8 \u03b25i", "\u03b25i respectively", "respectively shin ec", "shin ec et al.", "et al. 2006", "2006 bai m", "bai m et al.", "et al. 2014", "2014 santos r", "santos r et al.", "et al. 2017", "al. 2017 .", "2017 . this variation", ". this variation of", "this variation of the", "variation of the core", "of the core particle", "the core particle is", "core particle is known", "particle is known as", "is known as 20s", "known as 20s icp.", "as 20s icp. immunoproteasomes", "20s icp. immunoproteasomes utilize", "icp. immunoproteasomes utilize the", "immunoproteasomes utilize the pa28", "utilize the pa28 regulatory", "pa28 regulatory particle to", "regulatory particle to degrade", "particle to degrade antigens", "degrade antigens lesne", "antigens lesne j", "lesne j et al.", "al. 2021 .", "2021 . under inflammatory", ". under inflammatory conditions", "inflammatory conditions the", "conditions the expression", "the expression of the", "expression of the catalytic", "of the catalytic and", "the catalytic and pa28", "catalytic and pa28 regulatory", "and pa28 regulatory subunits", "pa28 regulatory subunits of", "regulatory subunits of immunoproteasome", "subunits of immunoproteasome is", "of immunoproteasome is induced", "immunoproteasome is induced by", "is induced by cytokines", "induced by cytokines like", "by cytokines like interferon", "cytokines like interferon gamma", "interferon gamma ifn\u03b3", "ifn\u03b3 type", "i interferons and", "interferons and tumor", "and tumor necrosis factor", "tumor necrosis factor alpha", "factor alpha tnf", "alpha tnf \u03b1", "tnf \u03b1 . immunoproteasomes", "\u03b1 . immunoproteasomes possess", ". immunoproteasomes possess enhanced", "immunoproteasomes possess enhanced chymotrypsin", "enhanced chymotrypsin and", "chymotrypsin and trypsin", "and trypsin like activities", "like activities alongside", "activities alongside with", "alongside with the reduced", "with the reduced caspase", "the reduced caspase like", "reduced caspase like activity.", "caspase like activity. these", "like activity. these distinct", "activity. these distinct enzymatic", "these distinct enzymatic properties", "distinct enzymatic properties of", "enzymatic properties of immunoproteasomes", "properties of immunoproteasomes generate", "of immunoproteasomes generate substrate", "immunoproteasomes generate substrate cleavage", "generate substrate cleavage patterns", "substrate cleavage patterns that", "cleavage patterns that enhance", "patterns that enhance loading", "that enhance loading of", "enhance loading of peptides", "loading of peptides onto", "of peptides onto the", "peptides onto the class", "onto the class i", "the class i mhc", "class i mhc for", "i mhc for immune", "mhc for immune presentation", "for immune presentation to", "immune presentation to ctl", "to ctl reviewed", "ctl reviewed by", "reviewed by tomko rj", "by tomko rj and", "tomko rj and hochstrasser", "rj and hochstrasser m", "and hochstrasser m 2013", "hochstrasser m 2013 .

              this", "m 2013 .

              this reactome", "2013 .

              this reactome module", ".

              this reactome module describes", "reactome module describes ub", "module describes ub independent", "describes ub independent antigen", "ub independent antigen processing", "independent antigen processing by", "antigen processing by pa28", "processing by pa28 20s", "by pa28 20s cp", "pa28 20s cp and", "20s cp and pa28", "cp and pa28 20s", "and pa28 20s icp", "pa28 20s icp proteasomes.", "intracellular foreign or aberrant host", "foreign or aberrant host proteins", "or aberrant host proteins are", "aberrant host proteins are cleaved", "host proteins are cleaved into", "proteins are cleaved into peptide", "are cleaved into peptide fragments", "cleaved into peptide fragments of", "into peptide fragments of a", "peptide fragments of a precise", "fragments of a precise size", "a precise size such", "precise size such that", "size such that they", "such that they can be", "that they can be loaded", "they can be loaded on", "can be loaded on to", "be loaded on to class", "loaded on to class i", "on to class i major", "to class i major histocompatibility", "class i major histocompatibility complex", "major histocompatibility complex mhc", "histocompatibility complex mhc i", "mhc i molecules and", "i molecules and presented", "molecules and presented externally to", "and presented externally to cytotoxic", "presented externally to cytotoxic cd8+", "externally to cytotoxic cd8+ t", "to cytotoxic cd8+ t lymphocytes", "cd8+ t lymphocytes ctls", "ctls reviewed by", "reviewed by embgenbroich m &", "by embgenbroich m & burgdorf", "embgenbroich m & burgdorf s", "m & burgdorf s 2018", "& burgdorf s 2018 .", "burgdorf s 2018 . in", "s 2018 . in the", "2018 . in the cytosol", "in the cytosol ctl", "the cytosol ctl recognized", "cytosol ctl recognized peptides", "ctl recognized peptides are generated", "recognized peptides are generated by", "peptides are generated by proteasomes", "generated by proteasomes which", "by proteasomes which exist", "proteasomes which exist as", "which exist as a mixture", "exist as a mixture of", "as a mixture of compositionally", "a mixture of compositionally distinct", "mixture of compositionally distinct complexes", "compositionally distinct complexes reviewed", "distinct complexes reviewed by", "complexes reviewed by kloetzel", "reviewed by kloetzel pm 2004", "kloetzel pm 2004 habib", "pm 2004 habib ja", "2004 habib ja et", "ja et al. 2022", "et al. 2022 .", "al. 2022 . the", "2022 . the proteasome complex", ". the proteasome complex consists", "the proteasome complex consists of", "proteasome complex consists of 20s", "complex consists of 20s proteolytic", "consists of 20s proteolytic core", "of 20s proteolytic core particle", "proteolytic core particle cp", "particle cp associated", "cp associated with a", "associated with a regulatory particle", "a regulatory particle rp", "particle rp such", "rp such as 19s", "such as 19s rp or", "as 19s rp or pa28", "19s rp or pa28 rp", "or pa28 rp zhao", "pa28 rp zhao j", "rp zhao j et", "zhao j et al. 2022", "et al. 2022 adolf", "al. 2022 adolf f", "2022 adolf f et", "f et al. 2024", "al. 2024 reviewed", "2024 reviewed by watanabe", "reviewed by watanabe a et", "by watanabe a et al.", "a et al. 2022", "2022 . the catalytic subunits", ". the catalytic subunits psmb6", "catalytic subunits psmb6 \u03b21", "\u03b22 and psmb5", "psmb5 \u03b25 within", "\u03b25 within 20s cp", "within 20s cp exhibit caspase", "20s cp exhibit caspase like", "exhibit caspase like trypsin", "caspase like trypsin like", "trypsin like and chymotrypsin", "like and chymotrypsin like", "chymotrypsin like activities respectively", "activities respectively vigneron", "respectively vigneron n et", "vigneron n et al. 2015", "et al. 2015 rut", "al. 2015 rut w", "2015 rut w &", "rut w & drag m", "w & drag m 2016", "& drag m 2016 .", "drag m 2016 . during", "m 2016 . during peptide", "2016 . during peptide bond", ". during peptide bond cleavage", "peptide bond cleavage threonine", "bond cleavage threonine from", "cleavage threonine from the", "threonine from the active site", "from the active site of", "the active site of the", "active site of the catalytic", "site of the catalytic \u03b2", "of the catalytic \u03b2 subunit", "the catalytic \u03b2 subunit binds", "catalytic \u03b2 subunit binds to", "\u03b2 subunit binds to the", "subunit binds to the n", "binds to the n terminal", "to the n terminal peptide", "the n terminal peptide fragment", "n terminal peptide fragment forming", "terminal peptide fragment forming an", "peptide fragment forming an unstable", "fragment forming an unstable acyl", "forming an unstable acyl enzyme", "an unstable acyl enzyme intermediate", "acyl enzyme intermediate where", "enzyme intermediate where a", "intermediate where a peptide", "where a peptide fragment remains", "a peptide fragment remains attached", "peptide fragment remains attached to", "fragment remains attached to the", "remains attached to the proteasome.", "attached to the proteasome. subsequently", "the proteasome. subsequently a", "proteasome. subsequently a water", "subsequently a water molecule", "a water molecule hydrolyzes the", "water molecule hydrolyzes the bond", "molecule hydrolyzes the bond between", "hydrolyzes the bond between the", "the bond between the peptide", "bond between the peptide and", "between the peptide and the", "the peptide and the proteasome", "and the proteasome resulting", "the proteasome resulting in", "proteasome resulting in the", "resulting in the release of", "in the release of the", "the release of the peptide's", "release of the peptide's c", "of the peptide's c terminal", "the peptide's c terminal end", "c terminal end mishto", "terminal end mishto m", "end mishto m et", "mishto m et al. 2012", "et al. 2012 ebstein", "al. 2012 ebstein f", "2012 ebstein f et", "ebstein f et al. 2016", "et al. 2016 soh", "al. 2016 soh wt", "2016 soh wt et", "wt et al. 2024", "et al. 2024 .", "al. 2024 . either", "2024 . either one or", ". either one or two", "either one or two regulatory", "one or two regulatory particles", "two regulatory particles rp", "particles rp can", "rp can attach to", "can attach to the 20s", "attach to the 20s cp", "the 20s cp zhao", "20s cp zhao j", "cp zhao j et", "2022 . the 19s rp", ". the 19s rp binds", "the 19s rp binds 20s", "19s rp binds 20s cp", "rp binds 20s cp to", "binds 20s cp to form", "20s cp to form the", "cp to form the 26s", "to form the 26s proteasome", "the 26s proteasome which", "26s proteasome which degrades", "proteasome which degrades both", "which degrades both foreign and", "degrades both foreign and self", "both foreign and self proteins", "foreign and self proteins in", "and self proteins in the", "self proteins in the ubiquitin", "in the ubiquitin ub", "atp dependent manner zhu", "dependent manner zhu y", "manner zhu y et", "y et al. 2018", "al. 2018 dong", "2018 dong y et", "y et al. 2019", "al. 2019 zhang", "2019 zhang s et", "s et al. 2022", "2022 reviewed by sahu", "reviewed by sahu i &", "by sahu i & glickman", "sahu i & glickman mh", "i & glickman mh 2021a", "& glickman mh 2021a .", "glickman mh 2021a . in", "mh 2021a . in addition", ". in addition a", "in addition a subset", "addition a subset of", "a subset of intracellular proteins", "of intracellular proteins especially", "intracellular proteins especially intrinsically", "proteins especially intrinsically disordered", "intrinsically disordered proteins can", "disordered proteins can directly", "proteins can directly bind", "can directly bind to 20s", "directly bind to 20s cp", "bind to 20s cp for", "to 20s cp for ub", "cp for ub and", "for ub and atp", "ub and atp independent", "and atp independent proteasomal degradation", "independent proteasomal degradation makaros", "proteasomal degradation makaros y", "degradation makaros y et", "y et al. 2023", "al. 2023 mamrosh", "2023 mamrosh jl et", "jl et al. 2023", "al. 2023 pepelnjak", "2023 pepelnjak m et", "m et al. 2024", "2024 reviewed by sahu", "i & glickman mh 2021", "& glickman mh 2021 b", "mh 2021 b bialek", "2021 b bialek w", "b bialek w et", "w et al. 2023", "al. 2023 . unlike", ". unlike 19s the", "unlike 19s the pa28", "19s the pa28 regulatory", "the pa28 regulatory particle does", "pa28 regulatory particle does not", "regulatory particle does not have", "particle does not have a", "does not have a ubiquitin", "not have a ubiquitin receptor", "a ubiquitin receptor binding", "ubiquitin receptor binding of", "receptor binding of pa28", "binding of pa28 to the", "of pa28 to the 20s", "pa28 to the 20s cp", "to the 20s cp promotes", "the 20s cp promotes ub", "promotes ub atp", "atp independent protein breakdown. pa28", "independent protein breakdown. pa28 proteasomes", "protein breakdown. pa28 proteasomes are", "breakdown. pa28 proteasomes are thought", "pa28 proteasomes are thought to", "proteasomes are thought to be", "are thought to be important", "thought to be important for", "to be important for rapid", "be important for rapid degradation", "important for rapid degradation of", "for rapid degradation of misfolded", "rapid degradation of misfolded proteins", "degradation of misfolded proteins under", "of misfolded proteins under conditions", "misfolded proteins under conditions of", "proteins under conditions of oxidative", "under conditions of oxidative stress", "conditions of oxidative stress or", "of oxidative stress or degradation", "oxidative stress or degradation of", "stress or degradation of proteins", "or degradation of proteins with", "degradation of proteins with intrinsically", "of proteins with intrinsically disordered", "proteins with intrinsically disordered regions", "intrinsically disordered regions habib", "disordered regions habib ja", "regions habib ja et", "ja et al. 2020", "al. 2020 chen", "2020 chen j et", "j et al. 2021", "al. 2021 zhao", "2021 zhao j et", "et al. 2022 reviewed", "al. 2022 reviewed by", "2022 reviewed by thomas", "reviewed by thomas t et", "by thomas t et al.", "thomas t et al. 2023", "t et al. 2023 .", "et al. 2023 . various", "al. 2023 . various immune", "2023 . various immune cells", "various immune cells such", "immune cells such as", "cells such as t", "as t cells b", "t cells b cells", "b cells and antigen", "cells and antigen presenting", "antigen presenting cells constitutively", "presenting cells constitutively express", "cells constitutively express a", "constitutively express a specialized form", "express a specialized form of", "a specialized form of proteasomes", "form of proteasomes known", "of proteasomes known as", "proteasomes known as immunoproteasomes", "known as immunoproteasomes in", "as immunoproteasomes in which", "immunoproteasomes in which the", "in which the catalytic subunits", "which the catalytic subunits psmb6", "psmb5 \u03b25 of", "\u03b25 of 20s cp", "of 20s cp are substituted", "20s cp are substituted with", "cp are substituted with psmb9", "substituted with psmb9 \u03b21i", "\u03b22i and psmb8", "respectively shin ec et", "ec et al. 2006", "al. 2006 bai", "2006 bai m et", "m et al. 2014", "al. 2014 santos", "2014 santos r et", "r et al. 2017", "et al. 2017 .", "al. 2017 . this", "2017 . this variation of", ". this variation of the", "this variation of the core", "variation of the core particle", "of the core particle is", "the core particle is known", "core particle is known as", "particle is known as 20s", "is known as 20s icp.", "known as 20s icp. immunoproteasomes", "as 20s icp. immunoproteasomes utilize", "20s icp. immunoproteasomes utilize the", "icp. immunoproteasomes utilize the pa28", "immunoproteasomes utilize the pa28 regulatory", "utilize the pa28 regulatory particle", "the pa28 regulatory particle to", "pa28 regulatory particle to degrade", "regulatory particle to degrade antigens", "to degrade antigens lesne", "degrade antigens lesne j", "antigens lesne j et", "j et al. 2020", "et al. 2021 .", "al. 2021 . under", "2021 . under inflammatory conditions", "under inflammatory conditions the", "inflammatory conditions the expression", "conditions the expression of", "the expression of the catalytic", "expression of the catalytic and", "of the catalytic and pa28", "the catalytic and pa28 regulatory", "catalytic and pa28 regulatory subunits", "and pa28 regulatory subunits of", "pa28 regulatory subunits of immunoproteasome", "regulatory subunits of immunoproteasome is", "subunits of immunoproteasome is induced", "of immunoproteasome is induced by", "immunoproteasome is induced by cytokines", "is induced by cytokines like", "induced by cytokines like interferon", "by cytokines like interferon gamma", "like interferon gamma ifn\u03b3", "ifn\u03b3 type i", "type i interferons and", "i interferons and tumor", "interferons and tumor necrosis", "and tumor necrosis factor alpha", "necrosis factor alpha tnf", "factor alpha tnf \u03b1", "alpha tnf \u03b1 .", "tnf \u03b1 . immunoproteasomes possess", "\u03b1 . immunoproteasomes possess enhanced", ". immunoproteasomes possess enhanced chymotrypsin", "possess enhanced chymotrypsin and", "enhanced chymotrypsin and trypsin", "chymotrypsin and trypsin like", "trypsin like activities alongside", "like activities alongside with", "activities alongside with the", "alongside with the reduced caspase", "with the reduced caspase like", "the reduced caspase like activity.", "reduced caspase like activity. these", "caspase like activity. these distinct", "like activity. these distinct enzymatic", "activity. these distinct enzymatic properties", "these distinct enzymatic properties of", "distinct enzymatic properties of immunoproteasomes", "enzymatic properties of immunoproteasomes generate", "properties of immunoproteasomes generate substrate", "of immunoproteasomes generate substrate cleavage", "immunoproteasomes generate substrate cleavage patterns", "generate substrate cleavage patterns that", "substrate cleavage patterns that enhance", "cleavage patterns that enhance loading", "patterns that enhance loading of", "that enhance loading of peptides", "enhance loading of peptides onto", "loading of peptides onto the", "of peptides onto the class", "peptides onto the class i", "onto the class i mhc", "the class i mhc for", "class i mhc for immune", "i mhc for immune presentation", "mhc for immune presentation to", "for immune presentation to ctl", "presentation to ctl reviewed", "to ctl reviewed by", "ctl reviewed by tomko", "reviewed by tomko rj and", "by tomko rj and hochstrasser", "tomko rj and hochstrasser m", "rj and hochstrasser m 2013", "and hochstrasser m 2013 .

              this", "hochstrasser m 2013 .

              this reactome", "m 2013 .

              this reactome module", "2013 .

              this reactome module describes", ".

              this reactome module describes ub", "reactome module describes ub independent", "module describes ub independent antigen", "describes ub independent antigen processing", "ub independent antigen processing by", "independent antigen processing by pa28", "antigen processing by pa28 20s", "processing by pa28 20s cp", "by pa28 20s cp and", "pa28 20s cp and pa28", "20s cp and pa28 20s", "cp and pa28 20s icp", "and pa28 20s icp proteasomes." ] }, { "record_id": "GLY_000594_1_2191", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9913351", "r hsa", "hsa 9913351", "r hsa 9913351" ] }, { "record_id": "GLY_000594_1_2191", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of the", "the dystrophin", "dystrophin glycoprotein", "glycoprotein complex", "formation of the", "of the dystrophin", "the dystrophin glycoprotein", "dystrophin glycoprotein complex", "complex dgc", "formation of the dystrophin", "of the dystrophin glycoprotein", "the dystrophin glycoprotein complex", "glycoprotein complex dgc", "formation of the dystrophin glycoprotein", "of the dystrophin glycoprotein complex", "dystrophin glycoprotein complex dgc", "also known", "known as", "as dapc", "dystrophin associated", "associated protein", "protein complex", "is a", "a large", "multimeric complex", "complex of", "of proteins", "proteins and", "and glycoproteins", "glycoproteins localized", "localized near", "near the", "the plasma", "plasma membrane", "membrane that", "that connects", "connects the", "the intracellular", "intracellular cell", "cell cytoskeleton", "cytoskeleton with", "with the", "the extracellular", "extracellular matrix", "matrix and", "and laminins", "reviewed in", "in bhat", "bhat et", "et al", "2018 .", ". in", "in muscle", "muscle cells", "the dgc", "dgc plays", "plays roles", "roles in", "in stabilizing", "stabilizing the", "the sarcolemma", "sarcolemma and", "and transducing", "transducing mechanical", "mechanical stimuli", "in wilson", "wilson et", "but dgc", "dgc complexes", "complexes are", "are found", "found in", "in several", "several other", "other cell", "cell types", "types and", "and tissues", "tissues and", "and play", "play more", "more general", "general roles", "in membrane", "membrane stability", "signal transduction", "transduction and", "and organization", "organization of", "of ion", "ion channels", "channels and", "and gaba", "gaba channels", "in waite", "waite et", "gawor and", "and pr\u00f3zy\u0144ski", ". while", "while mutations", "mutations in", "in some", "some components", "components of", "dgc are", "are reported", "reported to", "to make", "make muscle", "muscle fibers", "fibers more", "more susceptible", "susceptible to", "to damage", "damage and", "and lead", "lead to", "to various", "various types", "types of", "of muscle", "muscle disorder", "disorder such", "such as", "as duchenne", "duchenne muscular", "muscular dystrophy", "becker muscular", "limb girdle", "girdle muscular", "muscular dystrophies", "dystrophies and", "and cardiomyophathies", "straub and", "and campbell", "cohn and", "dgc components", "components have", "have also", "also been", "been associated", "associated with", "with disorders", "disorders in", "in non", "non muscle", "muscle tissue", "gumerson and", "and michele", "2011 .
              the", ".
              the core", "core of", "dgc is", "is made", "made up", "up of", "of dag1", "and utrophin.", "utrophin. dag1", "dag1 is", "is present", "present as", "as a", "a non", "non covalently", "covalently associated", "associated alpha", "alpha and", "and beta", "beta chain", "chain following", "following cleavage", "cleavage at", "at serine", "serine 654.", "654. extracellular", "extracellular alpha", "alpha dag1", "30 653", "contacts the", "matrix by", "by virtue", "virtue of", "of interactions", "interactions between", "between the", "the o", "o linked", "linked glycosyl", "glycosyl groups", "groups and", "while the", "the transmembrane", "transmembrane beta", "beta dag1", "dag1 684", "684 895", "interacts with", "the cytosolic", "cytosolic dystrophin", "dystrophin protein", "protein dmd.", "dmd.
              the", "
              the dgc", "dgc also", "also consists", "consists of", "of a", "a transmembrane", "transmembrane sarcoglycan", "sarcoglycan complex", "complex consisting", "consisting of", "of four", "four sarcoglycan", "and sspn", "sarcospan .", ". on", "on the", "the intracelluar", "intracelluar side", "dmd and", "dag1 recruit", "recruit membrane", "membrane associated", "associated cytosolic", "cytosolic proteins", "proteins including", "including members", "members of", "the dystrobrevin", "and syntrophin", "also known as", "known as dapc", "dapc dystrophin", "dystrophin associated protein", "associated protein complex", "complex is", "is a large", "large multimeric", "multimeric complex of", "complex of proteins", "of proteins and", "proteins and glycoproteins", "and glycoproteins localized", "glycoproteins localized near", "localized near the", "near the plasma", "the plasma membrane", "plasma membrane that", "membrane that connects", "that connects the", "connects the intracellular", "the intracellular cell", "intracellular cell cytoskeleton", "cell cytoskeleton with", "cytoskeleton with the", "with the extracellular", "the extracellular matrix", "extracellular matrix and", "matrix and laminins", "laminins reviewed", "reviewed in bhat", "in bhat et", "bhat et al", "al 2018", "2018 . in", ". in muscle", "in muscle cells", "cells the", "the dgc plays", "dgc plays roles", "plays roles in", "roles in stabilizing", "in stabilizing the", "stabilizing the sarcolemma", "the sarcolemma and", "sarcolemma and transducing", "and transducing mechanical", "transducing mechanical stimuli", "stimuli reviewed", "reviewed in wilson", "in wilson et", "wilson et al", "al 2022", "but dgc complexes", "dgc complexes are", "complexes are found", "are found in", "found in several", "in several other", "several other cell", "other cell types", "cell types and", "types and tissues", "and tissues and", "tissues and play", "and play more", "play more general", "more general roles", "general roles in", "roles in membrane", "in membrane stability", "stability signal", "signal transduction and", "transduction and organization", "and organization of", "organization of ion", "of ion channels", "ion channels and", "channels and gaba", "and gaba channels", "channels reviewed", "reviewed in waite", "in waite et", "waite et al", "al 2012", "2012 gawor", "gawor and pr\u00f3zy\u0144ski", "pr\u00f3zy\u0144ski 2018", "2018 bhat", "2018 . while", ". while mutations", "while mutations in", "mutations in some", "in some components", "some components of", "components of the", "of the dgc", "the dgc are", "dgc are reported", "are reported to", "reported to make", "to make muscle", "make muscle fibers", "muscle fibers more", "fibers more susceptible", "more susceptible to", "susceptible to damage", "to damage and", "damage and lead", "and lead to", "lead to various", "to various types", "various types of", "types of muscle", "of muscle disorder", "muscle disorder such", "disorder such as", "such as duchenne", "as duchenne muscular", "duchenne muscular dystrophy", "dystrophy becker", "becker muscular dystrophy", "dystrophy limb", "limb girdle muscular", "girdle muscular dystrophies", "muscular dystrophies and", "dystrophies and cardiomyophathies", "cardiomyophathies straub", "straub and campbell", "campbell 1997", "1997 cohn", "cohn and campbell", "campbell 2000", "dgc components have", "components have also", "have also been", "also been associated", "been associated with", "associated with disorders", "with disorders in", "disorders in non", "in non muscle", "non muscle tissue", "tissue gumerson", "gumerson and michele", "michele 2011", "2011 .
              the core", ".
              the core of", "core of the", "the dgc is", "dgc is made", "is made up", "made up of", "up of dag1", "dag1 dystroglycan", "dmd dystrophin", "dystrophin and", "and utrophin. dag1", "utrophin. dag1 is", "dag1 is present", "is present as", "present as a", "as a non", "a non covalently", "non covalently associated", "covalently associated alpha", "associated alpha and", "alpha and beta", "and beta chain", "beta chain following", "chain following cleavage", "following cleavage at", "cleavage at serine", "at serine 654.", "serine 654. extracellular", "654. extracellular alpha", "extracellular alpha dag1", "dag1 30", "653 contacts", "contacts the extracellular", "extracellular matrix by", "matrix by virtue", "by virtue of", "virtue of interactions", "of interactions between", "interactions between the", "between the o", "the o linked", "o linked glycosyl", "linked glycosyl groups", "glycosyl groups and", "groups and laminins", "laminins while", "while the transmembrane", "the transmembrane beta", "transmembrane beta dag1", "beta dag1 684", "dag1 684 895", "895 interacts", "interacts with the", "with the cytosolic", "the cytosolic dystrophin", "cytosolic dystrophin protein", "dystrophin protein dmd.", "protein dmd.
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              as", ".
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              the remaining", "remaining gaps", "gaps in", "strands are", "are ligated", "ligated by", "by the", "mitochondrial isoform", "isoform of", "of ligase", "ligase iii", "lig3 1", "2011 .", "the resulting", "resulting two", "two double", "stranded mitochondrial", "mitochondrial genomes", "genomes remain", "remain catenated", "catenated by", "single strands", "strands which", "which are", "are resolved", "resolved by", "by topoisomerase", "topoisomerase 3a", "nicholls et", "the human mitochondrial", "human mitochondrial genome", "mitochondrial genome is", "genome is a", "is a circular", "a circular double", "circular double stranded", "double stranded dna", "stranded dna of", "dna of 16569", "of 16569 bp", "16569 bp that", "bp that encodes", "that encodes 2", "encodes 2 rrnas", "rrnas 22", "trnas and", "and 13 proteins.", "13 proteins. based", "proteins. based on", "based on density", "on density in", "density in a", "in a denaturing", "a denaturing cesium", "denaturing cesium chloride", "cesium chloride gradient", "gradient a", "heavy h", "strand and a", "and a light", "light l", "strand are distinguishable.", "are distinguishable. two", "distinguishable. two basic", "two basic mechanisms", "basic mechanisms of", "mechanisms of mitochondrial", "of mitochondrial dna", "dna replication have", "replication have been", "have been proposed:", "proposed: 1", "1 strand", "strand asynchronous dna", "asynchronous dna replication", "replication also", "also called strand", "called strand displacement", "strand displacement dna", "displacement dna replication", "in which initiation", "which initiation of", "initiation of h", "of h strand", "h strand synthesis", "strand synthesis significantly", "synthesis significantly precedes", "significantly precedes initiation", "precedes initiation of", "initiation of l", "of l strand", "l strand synthesis", "strand synthesis and", "synthesis and each", "and each initiation", "each initiation is", "initiation is primed", "is primed at", "primed at a", "at a specific", "a specific origin", "origin and", "and 2", "2 strand", "strand synchronous dna", "synchronous dna replication", "called strand coupled", "strand coupled dna", "coupled dna replication", "replication in", "in which initiations", "which initiations of", "initiations of h", "synthesis and l", "and l strand", "strand synthesis occur", "synthesis occur concurrently", "occur concurrently and", "concurrently and are", "and are primed", "are primed by", "primed by short", "by short rna", "short rna primers", "rna primers distributed", "primers distributed through", "distributed through the", "through the genome", "genome yang", "yang et al.", "et al. 2002", "2002 reviewed", "reviewed in falkenberg", "in falkenberg 2018", "2018 yasukawa", "yasukawa and kang", "and kang 2018", "2018 shokolenko", "shokolenko and alexeyev", "and alexeyev 2022", "2022 falkenberg", "falkenberg et al.", "et al. 2024", "al. 2024 .", "2024 . both", ". both types", "both types of", "types of synthesis", "of synthesis may", "synthesis may occur", "may occur in", "occur in mitochondria", "in mitochondria and", "mitochondria and the", "and the choice", "the choice of", "choice of synthesis", "of synthesis type", "synthesis type may", "type may depend", "may depend on", "depend on the", "on the abundance", "the abundance of", "abundance of the", "of the dna", "the dna helicase", "dna helicase twinkle", "twinkle twnk", "twnk peo1", "peo1 and", "and rna transcripts", "transcripts cluett", "cluett et al.", "et al. 2018", "al. 2018 .", "2018 . the", ". the strand", "the strand asynchronous", "strand asynchronous model", "asynchronous model has", "model has existed", "has existed longer", "existed longer and", "longer and has", "and has been", "has been more", "been more completely", "more completely characterized", "characterized uhler", "uhler and falkenberg", "and falkenberg 2021", "2021 kosar", "kosar et al.", "et al. 2021", "al. 2021 .", "2021 . there", ". there is", "there is also", "is also some", "also some question", "some question of", "question of the", "of the evidence", "the evidence supporting", "evidence supporting the", "supporting the existence", "the existence of", "existence of rna", "of rna primers", "rna primers throughout", "primers throughout the", "throughout the genome", "genome brown", "brown et al.", "et al. 2005", "al. 2005 .
              in", "2005 .
              in the", ".
              in the strand", "strand asynchronous mechanism", "mechanism the", "the h strand", "h strand is", "strand is polymerized", "is polymerized first", "polymerized first from", "first from an", "from an origin", "an origin of", "origin of replication", "replication orih", "orih located", "located near the", "near the l", "the l strand", "l strand promoter", "promoter lsp", "which initiates transcription", "initiates transcription of", "transcription of the", "of the l", "l strand as", "strand as a", "as a template", "a template and", "template and a", "and a rna", "a rna corresponding", "rna corresponding to", "corresponding to the", "to the sequence", "the sequence of", "sequence of the", "of the h", "h strand as", "as a product", "product kang", "kang et al.", "et al. 1997", "1997 agaronyan", "agaronyan et al.", "et al. 2015", "2015 reviewed", "reviewed in kasiviswanathan", "in kasiviswanathan et", "kasiviswanathan et al.", "et al. 2012", "al. 2012 .", "2012 . the", ". the transcription", "the transcription elongation", "transcription elongation factor", "elongation factor tefm", "factor tefm acts", "tefm acts as", "acts as a", "as a switch", "a switch between", "switch between transcription", "between transcription of", "of the entire", "the entire l", "entire l strand", "l strand and", "strand and synthesis", "and synthesis of", "synthesis of a", "of a short", "a short primer", "short primer for", "primer for dna", "for dna replication", "replication agaronyan", "al. 2015 .", "2015 . the", ". the mitochondrial", "the mitochondrial rna", "mitochondrial rna polymerase", "rna polymerase polrmt", "polymerase polrmt at", "polrmt at lsp", "at lsp initiates", "lsp initiates synthesis", "initiates synthesis of", "synthesis of the", "h strand by", "strand by polymerizing", "by polymerizing a", "polymerizing a short", "a short rna", "short rna of", "rna of about", "of about 120", "about 120 nucleotides", "120 nucleotides that", "nucleotides that extends", "that extends from", "extends from the", "from the lsp", "the lsp to", "lsp to conserved", "to conserved sequence", "conserved sequence block", "sequence block 2", "2 csb2", "chang and clayton", "and clayton 1985", "1985 pham", "pham et al.", "et al. 2006", "al. 2006 .", "2006 . the", ". the 3'", "the 3' end", "3' end of", "end of the", "of the rna", "the rna is", "rna is located", "is located in", "located in a", "in a g", "a g quadruplex", "g quadruplex secondary", "quadruplex secondary structure", "secondary structure that", "structure that renders", "that renders the", "renders the 3'", "the 3' hydroxyl", "3' hydroxyl inaccessible", "hydroxyl inaccessible for", "inaccessible for priming", "for priming dna", "priming dna synthesis", "dna synthesis and", "synthesis and that", "and that creates", "that creates a", "creates a persistent", "a persistent r", "persistent r loop", "loop xu", "xu and clayton", "and clayton 1996", "1996 wanrooij", "wanrooij et al.", "et al. 2010", "2010 wanrooij", "2012 . rnaseh1", ". rnaseh1 cleaves", "rnaseh1 cleaves the", "cleaves the rna", "the rna in", "rna in the", "in the rna", "the rna dna", "rna dna duplex", "dna duplex and", "duplex and creates", "and creates accessible", "creates accessible 3'", "accessible 3' hydroxyl", "3' hydroxyl groups", "groups posse", "posse et al.", "et al. 2019", "2019 misic", "misic et al.", "et al. 2022", "al. 2022 .
              the", "2022 .
              the dna", ".
              the dna helicase", "and the mitochondrial", "the mitochondrial dna", "mitochondrial dna polymerase", "dna polymerase polgamma", "polgamma a", "a complex comprising", "complex comprising one", "comprising one subunit", "one subunit of", "subunit of polg", "of polg and", "polg and two", "and two subunits", "two subunits of", "subunits of polg2", "polg2 polg:polg2", "bind the orih", "the orih region", "region jemt", "jemt et al.", "et al. 2011", "2011 jemt", "2015 korhonen", "korhonen et al.", "et al. 2004", "al. 2004 .", "2004 . twnk", ". twnk binds", "twnk binds as", "binds as an", "as an open", "an open hexameric", "open hexameric ring", "hexameric ring that", "ring that closes", "that closes around", "closes around the", "around the dna", "the dna and", "dna and hydrolyzes", "and hydrolyzes atp", "hydrolyzes atp to", "atp to dissociate", "to dissociate double", "dissociate double stranded", "dna jemt", "2015 kaur", "kaur et al.", "et al. 2020", "2020 kaur", "2021 reviewed", "reviewed in peter", "in peter and", "peter and falkenberg", "and falkenberg 2020", "2020 ahead", "ahead of polgamma", "polgamma which", "which uses the", "uses the 3'", "hydroxyl groups of", "groups of the", "the rna at", "rna at orih", "at orih to", "orih to begin", "to begin polymerizing", "begin polymerizing the", "polymerizing the nascent", "the nascent h", "nascent h strand", "strand johnson", "johnson et al.", "et al. 2000", "2000 korhonen", "2004 wanrooij", "et al. 2008", "2008 plaza", "plaza g a", "g a et", "a et al.", "et al. 2023", "al. 2023 .", "2023 . as", ". as polymerization", "as polymerization proceeds", "proceeds the", "the parental h", "parental h strand", "strand is displaced", "is displaced and", "displaced and bound", "and bound by", "bound by single", "by single strand", "single strand binding", "strand binding protein", "binding protein 1", "1 ssbp1", "miralles fust\u00e9 et", "fust\u00e9 et al.", "et al. 2014", "2014 kaur", "2018 plaza", "2023 . there", "is also evidence", "also evidence of", "evidence of long", "of long rnas", "long rnas binding", "rnas binding the", "binding the displaced", "the displaced h", "displaced h strand", "strand the", "the \\bootlace\\ model", "model reyes", "reyes et al.", "et al. 2013", "al. 2013 .
              synthesis", "2013 .
              synthesis of", ".
              synthesis of the", "h strand continues", "strand continues until", "continues until polgamma", "until polgamma passes", "polgamma passes the", "passes the origin", "the origin of", "origin of l", "l strand replication", "replication oril", "oril about", "about two thirds", "two thirds of", "thirds of the", "of the way", "the way around", "way around the", "around the 16569", "the 16569 bp", "16569 bp genome.", "bp genome. oril", "genome. oril becomes", "oril becomes single", "becomes single stranded", "single stranded and", "stranded and assumes", "and assumes a", "assumes a secondary", "a secondary loop", "secondary loop structure", "loop structure that", "structure that binds", "that binds polrmt", "polrmt which", "which synthesizes a", "synthesizes a short", "short rna that", "rna that acts", "that acts as", "as a primer", "a primer for", "for dna synthesis", "synthesis wanrooij", "2008 fust\u00e9", "2010 sarfallah", "sarfallah et al.", "2021 . significantly", "significantly oril", "oril is required", "is required for", "required for mitochondrial", "for mitochondrial maintenance", "mitochondrial maintenance in", "maintenance in mice", "mice evidence", "evidence that the", "that the strand", "strand asynchronous replication", "asynchronous replication mechanism", "replication mechanism is", "mechanism is essential", "essential wanrooij", "al. 2012 .
              as", "2012 .
              as polgamma", ".
              as polgamma nears", "polgamma nears completion", "nears completion of", "completion of the", "the h and", "h and l", "and l strands", "strands it", "it migrates around", "migrates around the", "around the circular", "the circular genome", "circular genome and", "genome and reaches", "and reaches the", "reaches the 5'", "the 5' ends", "5' ends of", "ends of the", "the rna primers.", "rna primers. rnaseh1", "primers. rnaseh1 cleaves", "rnaseh1 cleaves all", "cleaves all but", "all but two", "but two ribonucleotides", "two ribonucleotides from", "ribonucleotides from the", "from the primers", "the primers in", "primers in the", "in the nascent", "nascent h and", "strands ruhanen", "ruhanen et al.", "2011 al", "al behadili et", "behadili et al.", "2018 reviewed", "reviewed in uhler", "in uhler and", "and falkenberg 2015", "falkenberg 2015 .", "2015 . subsequent", ". subsequent processing", "subsequent processing of", "processing of the", "l strands differs", "strands differs slightly.", "differs slightly. a", "slightly. a flap", "a flap structure", "flap structure appears", "structure appears to", "appears to be", "to be created", "be created by", "created by displacement", "by displacement at", "displacement at the", "at the 5'", "the 5' end", "5' end of", "h strand and", "strand and the", "and the flap", "the flap is", "flap is removed", "is removed by", "removed by mgme1", "mgme1 uhler", "uhler et al.", "et al. 2016", "al. 2016 .", "2016 . a", ". a similar", "a similar flap", "similar flap structure", "flap structure at", "structure at the", "l strand is", "strand is removed", "removed by another", "by another nuclease", "nuclease al", "2018 that", "that based", "based on in", "on in vitro", "in vitro evidence", "evidence may", "may be exog", "exog wu", "wu et al.", "2019 karlowicz", "karlowicz et al.", "2022 .
              the remaining", ".
              the remaining gaps", "remaining gaps in", "gaps in the", "in the h", "l strands are", "strands are ligated", "are ligated by", "ligated by the", "by the mitochondrial", "the mitochondrial isoform", "mitochondrial isoform of", "isoform of ligase", "of ligase iii", "iii lig3", "al. 2011 .", "2011 . the", ". the resulting", "the resulting two", "resulting two double", "two double stranded", "double stranded mitochondrial", "stranded mitochondrial genomes", "mitochondrial genomes remain", "genomes remain catenated", "remain catenated by", "catenated by single", "by single strands", "single strands which", "strands which are", "which are resolved", "are resolved by", "resolved by topoisomerase", "by topoisomerase 3a", "3a top3a", "nicholls et al.", "the human mitochondrial genome", "human mitochondrial genome is", "mitochondrial genome is a", "genome is a circular", "is a circular double", "a circular double stranded", "circular double stranded dna", "double stranded dna of", "stranded dna of 16569", "dna of 16569 bp", "of 16569 bp that", "16569 bp that encodes", "bp that encodes 2", "that encodes 2 rrnas", "2 rrnas 22", "rrnas 22 trnas", "22 trnas and", "trnas and 13", "and 13 proteins. based", "13 proteins. based on", "proteins. based on density", "based on density in", "on density in a", "density in a denaturing", "in a denaturing cesium", "a denaturing cesium chloride", "denaturing cesium chloride gradient", "chloride gradient a", "gradient a heavy", "a heavy h", "strand and a light", "a light l", "l strand are", "strand are distinguishable. two", "are distinguishable. two basic", "distinguishable. two basic mechanisms", "two basic mechanisms of", "basic mechanisms of mitochondrial", "mechanisms of mitochondrial dna", "of mitochondrial dna replication", "mitochondrial dna replication have", "dna replication have been", "replication have been proposed:", "been proposed: 1", "1 strand asynchronous", "strand asynchronous dna replication", "dna replication also", "replication also called", "also called strand displacement", "called strand displacement dna", "strand displacement dna replication", "in which initiation of", "which initiation of h", "initiation of h strand", "of h strand synthesis", "h strand synthesis significantly", "strand synthesis significantly precedes", "synthesis significantly precedes initiation", "significantly precedes initiation of", "precedes initiation of l", "initiation of l strand", "of l strand synthesis", "l strand synthesis and", "strand synthesis and each", "synthesis and each initiation", "and each initiation is", "each initiation is primed", "initiation is primed at", "is primed at a", "primed at a specific", "at a specific origin", "specific origin and", "2 strand synchronous", "strand synchronous dna replication", "also called strand coupled", "called strand coupled dna", "strand coupled dna replication", "dna replication in", "replication in which", "in which initiations of", "which initiations of h", "initiations of h strand", "h strand synthesis and", "strand synthesis and l", "synthesis and l strand", "and l strand synthesis", "l strand synthesis occur", "strand synthesis occur concurrently", "synthesis occur concurrently and", "occur concurrently and are", "concurrently and are primed", "and are primed by", "are primed by short", "primed by short rna", "by short rna primers", "short rna primers distributed", "rna primers distributed through", "primers distributed through the", "distributed through the genome", "the genome yang", "genome yang et", "yang et al. 2002", "al. 2002 reviewed", "2002 reviewed in", "reviewed in falkenberg 2018", "falkenberg 2018 yasukawa", "2018 yasukawa and", "yasukawa and kang 2018", "kang 2018 shokolenko", "2018 shokolenko and", "shokolenko and alexeyev 2022", "alexeyev 2022 falkenberg", "2022 falkenberg et", "falkenberg et al. 2024", "et al. 2024 .", "al. 2024 . both", "2024 . both types", ". both types of", "both types of synthesis", "types of synthesis may", "of synthesis may occur", "synthesis may occur in", "may occur in mitochondria", "occur in mitochondria and", "in mitochondria and the", "mitochondria and the choice", "and the choice of", "the choice of synthesis", "choice of synthesis type", "of synthesis type may", "synthesis type may depend", "type may depend on", "may depend on the", "depend on the abundance", "on the abundance of", "the abundance of the", "abundance of the dna", "of the dna helicase", "the dna helicase twinkle", "helicase twinkle twnk", "peo1 and rna", "rna transcripts cluett", "transcripts cluett et", "cluett et al. 2018", "et al. 2018 .", "al. 2018 . the", "2018 . the strand", ". the strand asynchronous", "the strand asynchronous model", "strand asynchronous model has", "asynchronous model has existed", "model has existed longer", "has existed longer and", "existed longer and has", "longer and has been", "and has been more", "has been more completely", "been more completely characterized", "completely characterized uhler", "characterized uhler and", "uhler and falkenberg 2021", "falkenberg 2021 kosar", "2021 kosar et", "kosar et al. 2021", "et al. 2021 .", "al. 2021 . there", "2021 . there is", ". there is also", "there is also some", "is also some question", "also some question of", "some question of the", "question of the evidence", "of the evidence supporting", "the evidence supporting the", "evidence supporting the existence", "supporting the existence of", "the existence of rna", "existence of rna primers", "of rna primers throughout", "rna primers throughout the", "primers throughout the genome", "the genome brown", "genome brown et", "brown et al. 2005", "et al. 2005 .
              in", "al. 2005 .
              in the", "2005 .
              in the strand", ".
              in the strand asynchronous", "the strand asynchronous mechanism", "asynchronous mechanism the", "mechanism the h", "the h strand is", "h strand is polymerized", "strand is polymerized first", "is polymerized first from", "polymerized first from an", "first from an origin", "from an origin of", "an origin of replication", "of replication orih", "orih located near", "located near the l", "near the l strand", "the l strand promoter", "strand promoter lsp", "lsp which", "which initiates transcription of", "initiates transcription of the", "transcription of the l", "of the l strand", "the l strand as", "l strand as a", "strand as a template", "as a template and", "a template and a", "template and a rna", "and a rna corresponding", "a rna corresponding to", "rna corresponding to the", "corresponding to the sequence", "to the sequence of", "the sequence of the", "sequence of the h", "of the h strand", "the h strand as", "h strand as a", "strand as a product", "a product kang", "product kang et", "kang et al. 1997", "al. 1997 agaronyan", "1997 agaronyan et", "agaronyan et al. 2015", "al. 2015 reviewed", "2015 reviewed in", "reviewed in kasiviswanathan et", "in kasiviswanathan et al.", "kasiviswanathan et al. 2012", "et al. 2012 .", "al. 2012 . the", "2012 . the transcription", ". the transcription elongation", "the transcription elongation factor", "transcription elongation factor tefm", "elongation factor tefm acts", "factor tefm acts as", "tefm acts as a", "acts as a switch", "as a switch between", "a switch between transcription", "switch between transcription of", "between transcription of the", "transcription of the entire", "of the entire l", "the entire l strand", "entire l strand and", "l strand and synthesis", "strand and synthesis of", "and synthesis of a", "synthesis of a short", "of a short primer", "a short primer for", "short primer for dna", "primer for dna replication", "dna replication agaronyan", "replication agaronyan et", "et al. 2015 .", "al. 2015 . the", "2015 . the mitochondrial", ". the mitochondrial rna", "the mitochondrial rna polymerase", "mitochondrial rna polymerase polrmt", "rna polymerase polrmt at", "polymerase polrmt at lsp", "polrmt at lsp initiates", "at lsp initiates synthesis", "lsp initiates synthesis of", "initiates synthesis of the", "synthesis of the h", "the h strand by", "h strand by polymerizing", "strand by polymerizing a", "by polymerizing a short", "polymerizing a short rna", "a short rna of", "short rna of about", "rna of about 120", "of about 120 nucleotides", "about 120 nucleotides that", "120 nucleotides that extends", "nucleotides that extends from", "that extends from the", "extends from the lsp", "from the lsp to", "the lsp to conserved", "lsp to conserved sequence", "to conserved sequence block", "conserved sequence block 2", "block 2 csb2", "csb2 chang", "chang and clayton 1985", "clayton 1985 pham", "1985 pham et", "pham et al. 2006", "et al. 2006 .", "al. 2006 . the", "2006 . the 3'", ". the 3' end", "the 3' end of", "3' end of the", "end of the rna", "of the rna is", "the rna is located", "rna is located in", "is located in a", "located in a g", "in a g quadruplex", "a g quadruplex secondary", "g quadruplex secondary structure", "quadruplex secondary structure that", "secondary structure that renders", "structure that renders the", "that renders the 3'", "renders the 3' hydroxyl", "the 3' hydroxyl inaccessible", "3' hydroxyl inaccessible for", "hydroxyl inaccessible for priming", "inaccessible for priming dna", "for priming dna synthesis", "priming dna synthesis and", "dna synthesis and that", "synthesis and that creates", "and that creates a", "that creates a persistent", "creates a persistent r", "a persistent r loop", "r loop xu", "loop xu and", "xu and clayton 1996", "clayton 1996 wanrooij", "1996 wanrooij et", "wanrooij et al. 2010", "al. 2010 wanrooij", "2010 wanrooij et", "wanrooij et al. 2012", "al. 2012 . rnaseh1", "2012 . rnaseh1 cleaves", ". rnaseh1 cleaves the", "rnaseh1 cleaves the rna", "cleaves the rna in", "the rna in the", "rna in the rna", "in the rna dna", "the rna dna duplex", "rna dna duplex and", "dna duplex and creates", "duplex and creates accessible", "and creates accessible 3'", "creates accessible 3' hydroxyl", "accessible 3' hydroxyl groups", "hydroxyl groups posse", "groups posse et", "posse et al. 2019", "al. 2019 misic", "2019 misic et", "misic et al. 2022", "et al. 2022 .
              the", "al. 2022 .
              the dna", "2022 .
              the dna helicase", ".
              the dna helicase twinkle", "peo1 and the", "and the mitochondrial dna", "the mitochondrial dna polymerase", "mitochondrial dna polymerase polgamma", "polymerase polgamma a", "polgamma a complex", "a complex comprising one", "complex comprising one subunit", "comprising one subunit of", "one subunit of polg", "subunit of polg and", "of polg and two", "polg and two subunits", "and two subunits of", "two subunits of polg2", "of polg2 polg:polg2", "polg:polg2 bind", "bind the orih region", "orih region jemt", "region jemt et", "jemt et al. 2011", "al. 2011 jemt", "2011 jemt et", "jemt et al. 2015", "al. 2015 korhonen", "2015 korhonen et", "korhonen et al. 2004", "et al. 2004 .", "al. 2004 . twnk", "2004 . twnk binds", ". twnk binds as", "twnk binds as an", "binds as an open", "as an open hexameric", "an open hexameric ring", "open hexameric ring that", "hexameric ring that closes", "ring that closes around", "that closes around the", "closes around the dna", "around the dna and", "the dna and hydrolyzes", "dna and hydrolyzes atp", "and hydrolyzes atp to", "hydrolyzes atp to dissociate", "atp to dissociate double", "to dissociate double stranded", "dissociate double stranded dna", "stranded dna jemt", "dna jemt et", "al. 2015 kaur", "2015 kaur et", "kaur et al. 2020", "al. 2020 kaur", "2020 kaur et", "kaur et al. 2021", "al. 2021 reviewed", "2021 reviewed in", "reviewed in peter and", "in peter and falkenberg", "peter and falkenberg 2020", "falkenberg 2020 ahead", "2020 ahead of", "of polgamma which", "polgamma which uses", "which uses the 3'", "uses the 3' hydroxyl", "the 3' hydroxyl groups", "3' hydroxyl groups of", "hydroxyl groups of the", "groups of the rna", "of the rna at", "the rna at orih", "rna at orih to", "at orih to begin", "orih to begin polymerizing", "to begin polymerizing the", "begin polymerizing the nascent", "polymerizing the nascent h", "the nascent h strand", "h strand johnson", "strand johnson et", "johnson et al. 2000", "al. 2000 korhonen", "2000 korhonen et", "al. 2004 wanrooij", "2004 wanrooij et", "wanrooij et al. 2008", "al. 2008 plaza", "2008 plaza g", "plaza g a et", "g a et al.", "a et al. 2023", "et al. 2023 .", "al. 2023 . as", "2023 . as polymerization", ". as polymerization proceeds", "polymerization proceeds the", "proceeds the parental", "the parental h strand", "parental h strand is", "h strand is displaced", "strand is displaced and", "is displaced and bound", "displaced and bound by", "and bound by single", "bound by single strand", "by single strand binding", "single strand binding protein", "strand binding protein 1", "protein 1 ssbp1", "ssbp1 miralles", "miralles fust\u00e9 et al.", "fust\u00e9 et al. 2014", "al. 2014 kaur", "2014 kaur et", "kaur et al. 2018", "al. 2018 plaza", "2018 plaza g", "al. 2023 . there", "2023 . there is", "there is also evidence", "is also evidence of", "also evidence of long", "evidence of long rnas", "of long rnas binding", "long rnas binding the", "rnas binding the displaced", "binding the displaced h", "the displaced h strand", "h strand the", "strand the \\bootlace\\", "\\bootlace\\ model reyes", "model reyes et", "reyes et al. 2013", "et al. 2013 .
              synthesis", "al. 2013 .
              synthesis of", "2013 .
              synthesis of the", ".
              synthesis of the h", "the h strand continues", "h strand continues until", "strand continues until polgamma", "continues until polgamma passes", "until polgamma passes the", "polgamma passes the origin", "passes the origin of", "the origin of l", "origin of l strand", "of l strand replication", "strand replication oril", "oril about two", "about two thirds of", "two thirds of the", "thirds of the way", "of the way around", "the way around the", "way around the 16569", "around the 16569 bp", "the 16569 bp genome.", "16569 bp genome. oril", "bp genome. oril becomes", "genome. oril becomes single", "oril becomes single stranded", "becomes single stranded and", "single stranded and assumes", "stranded and assumes a", "and assumes a secondary", "assumes a secondary loop", "a secondary loop structure", "secondary loop structure that", "loop structure that binds", "structure that binds polrmt", "binds polrmt which", "polrmt which synthesizes", "which synthesizes a short", "synthesizes a short rna", "a short rna that", "short rna that acts", "rna that acts as", "that acts as a", "acts as a primer", "as a primer for", "a primer for dna", "primer for dna synthesis", "dna synthesis wanrooij", "synthesis wanrooij et", "al. 2008 fust\u00e9", "2008 fust\u00e9 et", "fust\u00e9 et al. 2010", "al. 2010 sarfallah", "2010 sarfallah et", "sarfallah et al. 2021", "al. 2021 . significantly", ". significantly oril", "significantly oril is", "oril is required for", "is required for mitochondrial", "required for mitochondrial maintenance", "for mitochondrial maintenance in", "mitochondrial maintenance in mice", "in mice evidence", "mice evidence that", "evidence that the strand", "that the strand asynchronous", "the strand asynchronous replication", "strand asynchronous replication mechanism", "asynchronous replication mechanism is", "replication mechanism is essential", "is essential wanrooij", "essential wanrooij et", "et al. 2012 .
              as", "al. 2012 .
              as polgamma", "2012 .
              as polgamma nears", ".
              as polgamma nears completion", "polgamma nears completion of", "nears completion of the", "completion of the h", "of the h and", "the h and l", "h and l strands", "l strands it", "strands it migrates", "it migrates around the", "migrates around the circular", "around the circular genome", "the circular genome and", "circular genome and reaches", "genome and reaches the", "and reaches the 5'", "reaches the 5' ends", "the 5' ends of", "5' ends of the", "ends of the rna", "of the rna primers.", "the rna primers. rnaseh1", "rna primers. rnaseh1 cleaves", "primers. rnaseh1 cleaves all", "rnaseh1 cleaves all but", "cleaves all but two", "all but two ribonucleotides", "but two ribonucleotides from", "two ribonucleotides from the", "ribonucleotides from the primers", "from the primers in", "the primers in the", "primers in the nascent", "in the nascent h", "the nascent h and", "nascent h and l", "l strands ruhanen", "strands ruhanen et", "ruhanen et al. 2011", "al. 2011 al", "2011 al behadili", "al behadili et al.", "behadili et al. 2018", "al. 2018 reviewed", "2018 reviewed in", "reviewed in uhler and", "in uhler and falkenberg", "uhler and falkenberg 2015", "and falkenberg 2015 .", "falkenberg 2015 . subsequent", "2015 . subsequent processing", ". subsequent processing of", "subsequent processing of the", "processing of the h", "and l strands differs", "l strands differs slightly.", "strands differs slightly. a", "differs slightly. a flap", "slightly. a flap structure", "a flap structure appears", "flap structure appears to", "structure appears to be", "appears to be created", "to be created by", "be created by displacement", "created by displacement at", "by displacement at the", "displacement at the 5'", "at the 5' end", "the 5' end of", "5' end of the", "end of the h", "the h strand and", "h strand and the", "strand and the flap", "and the flap is", "the flap is removed", "flap is removed by", "is removed by mgme1", "by mgme1 uhler", "mgme1 uhler et", "uhler et al. 2016", "et al. 2016 .", "al. 2016 . a", "2016 . a similar", ". a similar flap", "a similar flap structure", "similar flap structure at", "flap structure at the", "structure at the 5'", "end of the l", "the l strand is", "l strand is removed", "strand is removed by", "is removed by another", "removed by another nuclease", "another nuclease al", "nuclease al behadili", "al. 2018 that", "that based on", "based on in vitro", "on in vitro evidence", "vitro evidence may", "evidence may be", "be exog wu", "exog wu et", "wu et al. 2019", "al. 2019 karlowicz", "2019 karlowicz et", "karlowicz et al. 2022", "al. 2022 .
              the remaining", "2022 .
              the remaining gaps", ".
              the remaining gaps in", "remaining gaps in the", "gaps in the h", "in the h and", "and l strands are", "l strands are ligated", "strands are ligated by", "are ligated by the", "ligated by the mitochondrial", "by the mitochondrial isoform", "the mitochondrial isoform of", "mitochondrial isoform of ligase", "isoform of ligase iii", "ligase iii lig3", "iii lig3 1", "1 ruhanen", "et al. 2011 .", "al. 2011 . the", "2011 . the resulting", ". the resulting two", "the resulting two double", "resulting two double stranded", "two double stranded mitochondrial", "double stranded mitochondrial genomes", "stranded mitochondrial genomes remain", "mitochondrial genomes remain catenated", "genomes remain catenated by", "remain catenated by single", "catenated by single strands", "by single strands which", "single strands which are", "strands which are resolved", "which are resolved by", "are resolved by topoisomerase", "resolved by topoisomerase 3a", "topoisomerase 3a top3a", "top3a nicholls", "nicholls et al. 2018", "the human mitochondrial genome is", "human mitochondrial genome is a", "mitochondrial genome is a circular", "genome is a circular double", "is a circular double stranded", "a circular double stranded dna", "circular double stranded dna of", "double stranded dna of 16569", "stranded dna of 16569 bp", "dna of 16569 bp that", "of 16569 bp that encodes", "16569 bp that encodes 2", "bp that encodes 2 rrnas", "encodes 2 rrnas 22", "2 rrnas 22 trnas", "22 trnas and 13", "trnas and 13 proteins.", "and 13 proteins. based on", "13 proteins. based on density", "proteins. based on density in", "based on density in a", "on density in a denaturing", "density in a denaturing cesium", "in a denaturing cesium chloride", "a denaturing cesium chloride gradient", "cesium chloride gradient a", "chloride gradient a heavy", "heavy h strand", "h strand and a", "and a light l", "light l strand", "l strand are distinguishable.", "strand are distinguishable. two basic", "are distinguishable. two basic mechanisms", "distinguishable. two basic mechanisms of", "two basic mechanisms of mitochondrial", "basic mechanisms of mitochondrial dna", "mechanisms of mitochondrial dna replication", "of mitochondrial dna replication have", "mitochondrial dna replication have been", "dna replication have been proposed:", "have been proposed: 1", "proposed: 1 strand", "1 strand asynchronous dna", "asynchronous dna replication also", "dna replication also called", "replication also called strand", "also called strand displacement dna", "called strand displacement dna replication", "in which initiation of h", "which initiation of h strand", "initiation of h strand synthesis", "of h strand synthesis significantly", "h strand synthesis significantly precedes", "strand synthesis significantly precedes initiation", "synthesis significantly precedes initiation of", "significantly precedes initiation of l", "precedes initiation of l strand", "initiation of l strand synthesis", "of l strand synthesis and", "l strand synthesis and each", "strand synthesis and each initiation", "synthesis and each initiation is", "and each initiation is primed", "each initiation is primed at", "initiation is primed at a", "is primed at a specific", "primed at a specific origin", "a specific origin and", "origin and 2", "and 2 strand", "2 strand synchronous dna", "synchronous dna replication also", "also called strand coupled dna", "called strand coupled dna replication", "coupled dna replication in", "dna replication in which", "replication in which initiations", "in which initiations of h", "which initiations of h strand", "initiations of h strand synthesis", "of h strand synthesis and", "h strand synthesis and l", "strand synthesis and l strand", "synthesis and l strand synthesis", "and l strand synthesis occur", "l strand synthesis occur concurrently", "strand synthesis occur concurrently and", "synthesis occur concurrently and are", "occur concurrently and are primed", "concurrently and are primed by", "and are primed by short", "are primed by short rna", "primed by short rna primers", "by short rna primers distributed", "short rna primers distributed through", "rna primers distributed through the", "primers distributed through the genome", "through the genome yang", "the genome yang et", "genome yang et al.", "et al. 2002 reviewed", "al. 2002 reviewed in", "2002 reviewed in falkenberg", "in falkenberg 2018 yasukawa", "falkenberg 2018 yasukawa and", "2018 yasukawa and kang", "and kang 2018 shokolenko", "kang 2018 shokolenko and", "2018 shokolenko and alexeyev", "and alexeyev 2022 falkenberg", "alexeyev 2022 falkenberg et", "2022 falkenberg et al.", "falkenberg et al. 2024 .", "et al. 2024 . both", "al. 2024 . both types", "2024 . both types of", ". both types of synthesis", "both types of synthesis may", "types of synthesis may occur", "of synthesis may occur in", "synthesis may occur in mitochondria", "may occur in mitochondria and", "occur in mitochondria and the", "in mitochondria and the choice", "mitochondria and the choice of", "and the choice of synthesis", "the choice of synthesis type", "choice of synthesis type may", "of synthesis type may depend", "synthesis type may depend on", "type may depend on the", "may depend on the abundance", "depend on the abundance of", "on the abundance of the", "the abundance of the dna", "abundance of the dna helicase", "of the dna helicase twinkle", "dna helicase twinkle twnk", "twinkle twnk peo1", "twnk peo1 and", "peo1 and rna transcripts", "and rna transcripts cluett", "rna transcripts cluett et", "transcripts cluett et al.", "cluett et al. 2018 .", "et al. 2018 . the", "al. 2018 . the strand", "2018 . the strand asynchronous", ". the strand asynchronous model", "the strand asynchronous model has", "strand asynchronous model has existed", "asynchronous model has existed longer", "model has existed longer and", "has existed longer and has", "existed longer and has been", "longer and has been more", "and has been more completely", "has been more completely characterized", "more completely characterized uhler", "completely characterized uhler and", "characterized uhler and falkenberg", "and falkenberg 2021 kosar", "falkenberg 2021 kosar et", "2021 kosar et al.", "kosar et al. 2021 .", "et al. 2021 . there", "al. 2021 . there is", "2021 . there is also", ". there is also some", "there is also some question", "is also some question of", "also some question of the", "some question of the evidence", "question of the evidence supporting", "of the evidence supporting the", "the evidence supporting the existence", "evidence supporting the existence of", "supporting the existence of rna", "the existence of rna primers", "existence of rna primers throughout", "of rna primers throughout the", "rna primers throughout the genome", "throughout the genome brown", "the genome brown et", "genome brown et al.", "brown et al. 2005 .
              in", "et al. 2005 .
              in the", "al. 2005 .
              in the strand", "2005 .
              in the strand asynchronous", ".
              in the strand asynchronous mechanism", "strand asynchronous mechanism the", "asynchronous mechanism the h", "mechanism the h strand", "the h strand is polymerized", "h strand is polymerized first", "strand is polymerized first from", "is polymerized first from an", "polymerized first from an origin", "first from an origin of", "from an origin of replication", "origin of replication orih", "replication orih located", "orih located near the", "located near the l strand", "near the l strand promoter", "l strand promoter lsp", "lsp which initiates", "which initiates transcription of the", "initiates transcription of the l", "transcription of the l strand", "of the l strand as", "the l strand as a", "l strand as a template", "strand as a template and", "as a template and a", "a template and a rna", "template and a rna corresponding", "and a rna corresponding to", "a rna corresponding to the", "rna corresponding to the sequence", "corresponding to the sequence of", "to the sequence of the", "the sequence of the h", "sequence of the h strand", "of the h strand as", "the h strand as a", "h strand as a product", "as a product kang", "a product kang et", "product kang et al.", "et al. 1997 agaronyan", "al. 1997 agaronyan et", "1997 agaronyan et al.", "et al. 2015 reviewed", "al. 2015 reviewed in", "2015 reviewed in kasiviswanathan", "reviewed in kasiviswanathan et al.", "in kasiviswanathan et al. 2012", "kasiviswanathan et al. 2012 .", "et al. 2012 . the", "al. 2012 . the transcription", "2012 . the transcription elongation", ". the transcription elongation factor", "the transcription elongation factor tefm", "transcription elongation factor tefm acts", "elongation factor tefm acts as", "factor tefm acts as a", "tefm acts as a switch", "acts as a switch between", "as a switch between transcription", "a switch between transcription of", "switch between transcription of the", "between transcription of the entire", "transcription of the entire l", "of the entire l strand", "the entire l strand and", "entire l strand and synthesis", "l strand and synthesis of", "strand and synthesis of a", "and synthesis of a short", "synthesis of a short primer", "of a short primer for", "a short primer for dna", "short primer for dna replication", "for dna replication agaronyan", "dna replication agaronyan et", "replication agaronyan et al.", "agaronyan et al. 2015 .", "et al. 2015 . the", "al. 2015 . the mitochondrial", "2015 . the mitochondrial rna", ". the mitochondrial rna polymerase", "the mitochondrial rna polymerase polrmt", "mitochondrial rna polymerase polrmt at", "rna polymerase polrmt at lsp", "polymerase polrmt at lsp initiates", "polrmt at lsp initiates synthesis", "at lsp initiates synthesis of", "lsp initiates synthesis of the", "initiates synthesis of the h", "synthesis of the h strand", "of the h strand by", "the h strand by polymerizing", "h strand by polymerizing a", "strand by polymerizing a short", "by polymerizing a short rna", "polymerizing a short rna of", "a short rna of about", "short rna of about 120", "rna of about 120 nucleotides", "of about 120 nucleotides that", "about 120 nucleotides that extends", "120 nucleotides that extends from", "nucleotides that extends from the", "that extends from the lsp", "extends from the lsp to", "from the lsp to conserved", "the lsp to conserved sequence", "lsp to conserved sequence block", "to conserved sequence block 2", "sequence block 2 csb2", "csb2 chang and", "and clayton 1985 pham", "clayton 1985 pham et", "1985 pham et al.", "pham et al. 2006 .", "et al. 2006 . the", "al. 2006 . the 3'", "2006 . the 3' end", ". the 3' end of", "the 3' end of the", "3' end of the rna", "end of the rna is", "of the rna is located", "the rna is located in", "rna is located in a", "is located in a g", "located in a g quadruplex", "in a g quadruplex secondary", "a g quadruplex secondary structure", "g quadruplex secondary structure that", "quadruplex secondary structure that renders", "secondary structure that renders the", "structure that renders the 3'", "that renders the 3' hydroxyl", "renders the 3' hydroxyl inaccessible", "the 3' hydroxyl inaccessible for", "3' hydroxyl inaccessible for priming", "hydroxyl inaccessible for priming dna", "inaccessible for priming dna synthesis", "for priming dna synthesis and", "priming dna synthesis and that", "dna synthesis and that creates", "synthesis and that creates a", "and that creates a persistent", "that creates a persistent r", "creates a persistent r loop", "persistent r loop xu", "r loop xu and", "loop xu and clayton", "and clayton 1996 wanrooij", "clayton 1996 wanrooij et", "1996 wanrooij et al.", "et al. 2010 wanrooij", "al. 2010 wanrooij et", "2010 wanrooij et al.", "wanrooij et al. 2012 .", "et al. 2012 . rnaseh1", "al. 2012 . rnaseh1 cleaves", "2012 . rnaseh1 cleaves the", ". rnaseh1 cleaves the rna", "rnaseh1 cleaves the rna in", "cleaves the rna in the", "the rna in the rna", "rna in the rna dna", "in the rna dna duplex", "the rna dna duplex and", "rna dna duplex and creates", "dna duplex and creates accessible", "duplex and creates accessible 3'", "and creates accessible 3' hydroxyl", "creates accessible 3' hydroxyl groups", "3' hydroxyl groups posse", "hydroxyl groups posse et", "groups posse et al.", "et al. 2019 misic", "al. 2019 misic et", "2019 misic et al.", "misic et al. 2022 .
              the", "et al. 2022 .
              the dna", "al. 2022 .
              the dna helicase", "2022 .
              the dna helicase twinkle", "peo1 and the mitochondrial", "and the mitochondrial dna polymerase", "the mitochondrial dna polymerase polgamma", "dna polymerase polgamma a", "polymerase polgamma a complex", "polgamma a complex comprising", "a complex comprising one subunit", "complex comprising one subunit of", "comprising one subunit of polg", "one subunit of polg and", "subunit of polg and two", "of polg and two subunits", "polg and two subunits of", "and two subunits of polg2", "subunits of polg2 polg:polg2", "polg:polg2 bind the", "the orih region jemt", "orih region jemt et", "region jemt et al.", "et al. 2011 jemt", "al. 2011 jemt et", "2011 jemt et al.", "et al. 2015 korhonen", "al. 2015 korhonen et", "2015 korhonen et al.", "korhonen et al. 2004 .", "et al. 2004 . twnk", "al. 2004 . twnk binds", "2004 . twnk binds as", ". twnk binds as an", "twnk binds as an open", "binds as an open hexameric", "as an open hexameric ring", "an open hexameric ring that", "open hexameric ring that closes", "hexameric ring that closes around", "ring that closes around the", "that closes around the dna", "closes around the dna and", "around the dna and hydrolyzes", "the dna and hydrolyzes atp", "dna and hydrolyzes atp to", "and hydrolyzes atp to dissociate", "hydrolyzes atp to dissociate double", "atp to dissociate double stranded", "to dissociate double stranded dna", "double stranded dna jemt", "stranded dna jemt et", "dna jemt et al.", "et al. 2015 kaur", "al. 2015 kaur et", "2015 kaur et al.", "et al. 2020 kaur", "al. 2020 kaur et", "2020 kaur et al.", "et al. 2021 reviewed", "al. 2021 reviewed in", "2021 reviewed in peter", "reviewed in peter and falkenberg", "in peter and falkenberg 2020", "and falkenberg 2020 ahead", "falkenberg 2020 ahead of", "2020 ahead of polgamma", "ahead of polgamma which", "of polgamma which uses", "polgamma which uses the", "which uses the 3' hydroxyl", "uses the 3' hydroxyl groups", "the 3' hydroxyl groups of", "3' hydroxyl groups of the", "hydroxyl groups of the rna", "groups of the rna at", "of the rna at orih", "the rna at orih to", "rna at orih to begin", "at orih to begin polymerizing", "orih to begin polymerizing the", "to begin polymerizing the nascent", "begin polymerizing the nascent h", "polymerizing the nascent h strand", "nascent h strand johnson", "h strand johnson et", "strand johnson et al.", "et al. 2000 korhonen", "al. 2000 korhonen et", "2000 korhonen et al.", "et al. 2004 wanrooij", "al. 2004 wanrooij et", "2004 wanrooij et al.", "et al. 2008 plaza", "al. 2008 plaza g", "2008 plaza g a", "plaza g a et al.", "g a et al. 2023", "a et al. 2023 .", "et al. 2023 . as", "al. 2023 . as polymerization", "2023 . as polymerization proceeds", "as polymerization proceeds the", "polymerization proceeds the parental", "proceeds the parental h", "the parental h strand is", "parental h strand is displaced", "h strand is displaced and", "strand is displaced and bound", "is displaced and bound by", "displaced and bound by single", "and bound by single strand", "bound by single strand binding", "by single strand binding protein", "single strand binding protein 1", "binding protein 1 ssbp1", "ssbp1 miralles fust\u00e9", "miralles fust\u00e9 et al. 2014", "et al. 2014 kaur", "al. 2014 kaur et", "2014 kaur et al.", "et al. 2018 plaza", "al. 2018 plaza g", "2018 plaza g a", "et al. 2023 . there", "al. 2023 . there is", "2023 . there is also", ". there is also evidence", "there is also evidence of", "is also evidence of long", "also evidence of long rnas", "evidence of long rnas binding", "of long rnas binding the", "long rnas binding the displaced", "rnas binding the displaced h", "binding the displaced h strand", "displaced h strand the", "h strand the \\bootlace\\", "strand the \\bootlace\\ model", "the \\bootlace\\ model reyes", "\\bootlace\\ model reyes et", "model reyes et al.", "reyes et al. 2013 .
              synthesis", "et al. 2013 .
              synthesis of", "al. 2013 .
              synthesis of the", "2013 .
              synthesis of the h", ".
              synthesis of the h strand", "of the h strand continues", "the h strand continues until", "h strand continues until polgamma", "strand continues until polgamma passes", "continues until polgamma passes the", "until polgamma passes the origin", "polgamma passes the origin of", "passes the origin of l", "the origin of l strand", "origin of l strand replication", "l strand replication oril", "replication oril about", "oril about two thirds", "about two thirds of the", "two thirds of the way", "thirds of the way around", "of the way around the", "the way around the 16569", "way around the 16569 bp", "around the 16569 bp genome.", "the 16569 bp genome. oril", "16569 bp genome. oril becomes", "bp genome. oril becomes single", "genome. oril becomes single stranded", "oril becomes single stranded and", "becomes single stranded and assumes", "single stranded and assumes a", "stranded and assumes a secondary", "and assumes a secondary loop", "assumes a secondary loop structure", "a secondary loop structure that", "secondary loop structure that binds", "loop structure that binds polrmt", "that binds polrmt which", "binds polrmt which synthesizes", "polrmt which synthesizes a", "which synthesizes a short rna", "synthesizes a short rna that", "a short rna that acts", "short rna that acts as", "rna that acts as a", "that acts as a primer", "acts as a primer for", "as a primer for dna", "a primer for dna synthesis", "for dna synthesis wanrooij", "dna synthesis wanrooij et", "synthesis wanrooij et al.", "et al. 2008 fust\u00e9", "al. 2008 fust\u00e9 et", "2008 fust\u00e9 et al.", "et al. 2010 sarfallah", "al. 2010 sarfallah et", "2010 sarfallah et al.", "sarfallah et al. 2021 .", "et al. 2021 . significantly", "2021 . significantly oril", ". significantly oril is", "significantly oril is required", "oril is required for mitochondrial", "is required for mitochondrial maintenance", "required for mitochondrial maintenance in", "for mitochondrial maintenance in mice", "maintenance in mice evidence", "in mice evidence that", "mice evidence that the", "evidence that the strand asynchronous", "that the strand asynchronous replication", "the strand asynchronous replication mechanism", "strand asynchronous replication mechanism is", "asynchronous replication mechanism is essential", "mechanism is essential wanrooij", "is essential wanrooij et", "essential wanrooij et al.", "wanrooij et al. 2012 .
              as", "et al. 2012 .
              as polgamma", "al. 2012 .
              as polgamma nears", "2012 .
              as polgamma nears completion", ".
              as polgamma nears completion of", "polgamma nears completion of the", "nears completion of the h", "completion of the h and", "of the h and l", "the h and l strands", "and l strands it", "l strands it migrates", "strands it migrates around", "it migrates around the circular", "migrates around the circular genome", "around the circular genome and", "the circular genome and reaches", "circular genome and reaches the", "genome and reaches the 5'", "and reaches the 5' ends", "reaches the 5' ends of", "the 5' ends of the", "5' ends of the rna", "ends of the rna primers.", "of the rna primers. rnaseh1", "the rna primers. rnaseh1 cleaves", "rna primers. rnaseh1 cleaves all", "primers. rnaseh1 cleaves all but", "rnaseh1 cleaves all but two", "cleaves all but two ribonucleotides", "all but two ribonucleotides from", "but two ribonucleotides from the", "two ribonucleotides from the primers", "ribonucleotides from the primers in", "from the primers in the", "the primers in the nascent", "primers in the nascent h", "in the nascent h and", "the nascent h and l", "nascent h and l strands", "and l strands ruhanen", "l strands ruhanen et", "strands ruhanen et al.", "et al. 2011 al", "al. 2011 al behadili", "2011 al behadili et", "al behadili et al. 2018", "et al. 2018 reviewed", "al. 2018 reviewed in", "2018 reviewed in uhler", "reviewed in uhler and falkenberg", "in uhler and falkenberg 2015", "uhler and falkenberg 2015 .", "and falkenberg 2015 . subsequent", "falkenberg 2015 . subsequent processing", "2015 . subsequent processing of", ". subsequent processing of the", "subsequent processing of the h", "processing of the h and", "h and l strands differs", "and l strands differs slightly.", "l strands differs slightly. a", "strands differs slightly. a flap", "differs slightly. a flap structure", "slightly. a flap structure appears", "a flap structure appears to", "flap structure appears to be", "structure appears to be created", "appears to be created by", "to be created by displacement", "be created by displacement at", "created by displacement at the", "by displacement at the 5'", "displacement at the 5' end", "at the 5' end of", "the 5' end of the", "5' end of the h", "end of the h strand", "of the h strand and", "the h strand and the", "h strand and the flap", "strand and the flap is", "and the flap is removed", "the flap is removed by", "flap is removed by mgme1", "removed by mgme1 uhler", "by mgme1 uhler et", "mgme1 uhler et al.", "uhler et al. 2016 .", "et al. 2016 . a", "al. 2016 . a similar", "2016 . a similar flap", ". a similar flap structure", "a similar flap structure at", "similar flap structure at the", "flap structure at the 5'", "structure at the 5' end", "5' end of the l", "end of the l strand", "of the l strand is", "the l strand is removed", "l strand is removed by", "strand is removed by another", "is removed by another nuclease", "by another nuclease al", "another nuclease al behadili", "nuclease al behadili et", "et al. 2018 that", "2018 that based", "that based on in", "based on in vitro evidence", "in vitro evidence may", "vitro evidence may be", "evidence may be exog", "may be exog wu", "be exog wu et", "exog wu et al.", "et al. 2019 karlowicz", "al. 2019 karlowicz et", "2019 karlowicz et al.", "karlowicz et al. 2022 .
              the", "et al. 2022 .
              the remaining", "al. 2022 .
              the remaining gaps", "2022 .
              the remaining gaps in", ".
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              ductal epithelial", "epithelial cells", "cells line", "line the", "the pancreatic", "pancreatic ducts", "ducts in", "in a", "a single", "single layer", "changing the", "the shape", "shape as", "as ducts", "ducts increase", "increase in", "in size", "size from", "from cuboidal", "through low", "low columnar", "to high", "high columnar", "columnar epithelium", "liggitt and", "and dintzis", "pp. 241", "241 250", "250 .", ". ductal", "ductal epithelial", "cells may", "may have", "have cilia", "cilia or", "or microvilli", "microvilli on", "on their", "their apical", "apical surface", ". besides", "besides ductal", "main pancreatic", "ducts sometimes", "sometimes include", "include goblet", "goblet cells", "250 .

              ductal", ".

              ductal epithelial", "cells develop", "develop from", "from bipotent", "bipotent pancreatic", "pancreatic trunk", "trunk progenitor", "progenitor cells", "which also", "also give", "give rise", "rise to", "to endocrine", "endocrine progenitors", "progenitors and", "and are", "are derived", "derived from", "from the", "the primary", "primary multipotent", "multipotent pancreatic", "pancreatic progenitor", "reviewed in", "in shih", "shih et", "et al.", "al. 2013", "jennings et", "al. 2015", "2015 .

              ", "

              ductal epithelial cells", "epithelial cells line", "cells line the", "line the pancreatic", "the pancreatic ducts", "pancreatic ducts in", "ducts in a", "in a single", "a single layer", "layer changing", "changing the shape", "the shape as", "shape as ducts", "as ducts increase", "ducts increase in", "increase in size", "in size from", "size from cuboidal", "cuboidal through", "through low columnar", "columnar to", "to high columnar", "high columnar epithelium", "epithelium liggitt", "liggitt and dintzis", "dintzis \u201cpancreas\u201d", "\u201cpancreas\u201d pp.", "pp. 241 250", "241 250 .", "250 . ductal", ". ductal epithelial", "ductal epithelial cells", "epithelial cells may", "cells may have", "may have cilia", "have cilia or", "cilia or microvilli", "or microvilli on", "microvilli on their", "on their apical", "their apical surface", "surface liggitt", "250 . besides", ". besides ductal", "besides ductal epithelial", "cells main", "main pancreatic ducts", "pancreatic ducts sometimes", "ducts sometimes include", "sometimes include goblet", "include goblet cells", "cells liggitt", "241 250 .

              ductal", "250 .

              ductal epithelial", ".

              ductal epithelial cells", "epithelial cells develop", "cells develop from", "develop from bipotent", "from bipotent pancreatic", "bipotent pancreatic trunk", "pancreatic trunk progenitor", "trunk progenitor cells", "cells which", "which also give", "also give rise", "give rise to", "rise to endocrine", "to endocrine progenitors", "endocrine progenitors and", "progenitors and are", "and are derived", "are derived from", "derived from the", "from the primary", "the primary multipotent", "primary multipotent pancreatic", "multipotent pancreatic progenitor", "pancreatic progenitor cells", "cells reviewed", "reviewed in shih", "in shih et", "shih et al.", "et al. 2013", "2013 jennings", "jennings et al.", "et al. 2015", "al. 2015 .

              ", "

              ductal epithelial cells line", "epithelial cells line the", "cells line the pancreatic", "line the pancreatic ducts", "the pancreatic ducts in", "pancreatic ducts in a", "ducts in a single", "in a single layer", "single layer changing", "layer changing the", "changing the shape as", "the shape as ducts", "shape as ducts increase", "as ducts increase in", "ducts increase in size", "increase in size from", "in size from cuboidal", "from cuboidal through", "cuboidal through low", "low columnar to", "columnar to high", "to high columnar epithelium", "columnar epithelium liggitt", "epithelium liggitt and", "and dintzis \u201cpancreas\u201d", "\u201cpancreas\u201d pp. 241", "pp. 241 250 .", "241 250 . ductal", "250 . ductal epithelial", ". ductal epithelial cells", "ductal epithelial cells may", "epithelial cells may have", "cells may have cilia", "may have cilia or", "have cilia or microvilli", "cilia or microvilli on", "or microvilli on their", "microvilli on their apical", "on their apical surface", "apical surface liggitt", "surface liggitt and", "241 250 . besides", "250 . besides ductal", ". besides ductal epithelial", "besides ductal epithelial cells", "epithelial cells main", "cells main pancreatic", "main pancreatic ducts sometimes", "pancreatic ducts sometimes include", "ducts sometimes include goblet", "sometimes include goblet cells", "goblet cells liggitt", "cells liggitt and", "pp. 241 250 .

              ductal", "241 250 .

              ductal epithelial", "250 .

              ductal epithelial cells", ".

              ductal epithelial cells develop", "epithelial cells develop from", "cells develop from bipotent", "develop from bipotent pancreatic", "from bipotent pancreatic trunk", "bipotent pancreatic trunk progenitor", "pancreatic trunk progenitor cells", "progenitor cells which", "cells which also", "which also give rise", "also give rise to", "give rise to endocrine", "rise to endocrine progenitors", "to endocrine progenitors and", "endocrine progenitors and are", "progenitors and are derived", "and are derived from", "are derived from the", "derived from the primary", "from the primary multipotent", "the primary multipotent pancreatic", "primary multipotent pancreatic progenitor", "multipotent pancreatic progenitor cells", "progenitor cells reviewed", "cells reviewed in", "reviewed in shih et", "in shih et al.", "shih et al. 2013", "al. 2013 jennings", "2013 jennings et", "jennings et al. 2015", "et al. 2015 .

              ", "

              ductal epithelial cells line the", "epithelial cells line the pancreatic", "cells line the pancreatic ducts", "line the pancreatic ducts in", "the pancreatic ducts in a", "pancreatic ducts in a single", "ducts in a single layer", "a single layer changing", "single layer changing the", "layer changing the shape", "changing the shape as ducts", "the shape as ducts increase", "shape as ducts increase in", "as ducts increase in size", "ducts increase in size from", "increase in size from cuboidal", "size from cuboidal through", "from cuboidal through low", "cuboidal through low columnar", "through low columnar to", "low columnar to high", "columnar to high columnar", "high columnar epithelium liggitt", "columnar epithelium liggitt and", "epithelium liggitt and dintzis", "liggitt and dintzis \u201cpancreas\u201d", "dintzis \u201cpancreas\u201d pp.", "\u201cpancreas\u201d pp. 241 250", "pp. 241 250 . ductal", "241 250 . ductal epithelial", "250 . ductal epithelial cells", ". ductal epithelial cells may", "ductal epithelial cells may have", "epithelial cells may have cilia", "cells may have cilia or", "may have cilia or microvilli", "have cilia or microvilli on", "cilia or microvilli on their", "or microvilli on their apical", "microvilli on their apical surface", "their apical surface liggitt", "apical surface liggitt and", "surface liggitt and dintzis", "pp. 241 250 . besides", "241 250 . besides ductal", "250 . besides ductal epithelial", ". besides ductal epithelial cells", "ductal epithelial cells main", "epithelial cells main pancreatic", "cells main pancreatic ducts", "main pancreatic ducts sometimes include", "pancreatic ducts sometimes include goblet", "ducts sometimes include goblet cells", "include goblet cells liggitt", "goblet cells liggitt and", "cells liggitt and dintzis", "pp. 241 250 .

              ductal epithelial", "241 250 .

              ductal epithelial cells", "250 .

              ductal epithelial cells develop", ".

              ductal epithelial cells develop from", "epithelial cells develop from bipotent", "cells develop from bipotent pancreatic", "develop from bipotent pancreatic trunk", "from bipotent pancreatic trunk progenitor", "bipotent pancreatic trunk progenitor cells", "trunk progenitor cells which", "progenitor cells which also", "cells which also give", "which also give rise to", "also give rise to endocrine", "give rise to endocrine progenitors", "rise to endocrine progenitors and", "to endocrine progenitors and are", "endocrine progenitors and are derived", "progenitors and are derived from", "and are derived from the", "are derived from the primary", "derived from the primary multipotent", "from the primary multipotent pancreatic", "the primary multipotent pancreatic progenitor", "primary multipotent pancreatic progenitor cells", "pancreatic progenitor cells reviewed", "progenitor cells reviewed in", "cells reviewed in shih", "reviewed in shih et al.", "in shih et al. 2013", "et al. 2013 jennings", "al. 2013 jennings et", "2013 jennings et al.", "jennings et al. 2015 .

              " ] }, { "record_id": "GLY_000594_1_2194", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9927354", "r hsa", "hsa 9927354", "r hsa 9927354" ] }, { "record_id": "GLY_000594_1_2194", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "co stimulation", "stimulation by", "by icos", "co stimulation by", "stimulation by icos", "co stimulation by icos", "inducible t", "t cell", "cell costimulator", "is a", "a critical", "critical costimulatory", "costimulatory receptor", "receptor that", "that enhances", "enhances t", "cell responses", "responses following", "following initial", "initial activation.", "activation. unlike", "unlike cd28", "which is", "is constitutively", "constitutively expressed", "expressed on", "on naive", "naive t", "t cells", "icos expression", "expression is", "is induced", "induced upon", "upon t", "cell activation.", "activation. both", "both icos", "icos and", "and 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"cell responses following", "responses following initial", "following initial activation.", "initial activation. unlike", "activation. unlike cd28", "cd28 which", "which is constitutively", "is constitutively expressed", "constitutively expressed on", "expressed on naive", "on naive t", "naive t cells", "cells icos", "icos expression is", "expression is induced", "is induced upon", "induced upon t", "upon t cell", "t cell activation.", "cell activation. both", "activation. both icos", "both icos and", "icos and cd28", "and cd28 engage", "cd28 engage class", "engage class ia", "class ia phosphatidylinositol", "ia phosphatidylinositol 3", "phosphatidylinositol 3 kinase", "kinase pi3k", "leading to the", "to the production", "the production of", "production of phosphatidylinositol", "of phosphatidylinositol 3", "phosphatidylinositol 3 4", "3 4 5", "4 5 trisphosphate", "trisphosphate pip3", "pip3 and", "and activation of", "activation of downstream", "of downstream signaling", "downstream 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              the", "2009 .
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              ror", "links with metabolism.
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              the", "al. 2009 .
              the genes", "2009 .
              the genes encoding", ".
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              mammalian cbaf", ".
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              mammalian", "2023 .
              mammalian cbaf complexes", ".
              mammalian cbaf complexes are", "cbaf complexes are required", "complexes are required for", "are required for chromatin", "required for chromatin remodelling", "for chromatin remodelling and", "chromatin remodelling and oppose", "remodelling and oppose polycomb", "and oppose polycomb repression", "polycomb repression kadoch", "repression kadoch et", "et al 2017", "2017 stanton et", "2017 wilson et", "et al 2010", "al 2010 .", "2010 . unlike in", ". unlike in yeast", "in yeast however", "however mammalian cbaf", "mammalian cbaf complexes are", "cbaf complexes are able", "complexes are able to", "are able to support", "able to support both", "to support both gene", "support both gene activation", "both gene activation and", "gene activation and repression", "and repression boyer", "repression boyer et", "et al 2005", "2005 ho et", "et al 2009", "al 2009 .", "the mammalian canonical brg1 associated", "mammalian canonical brg1 associated factors", "brg1 associated factors baf", "factors baf complex", "baf complex is the", "complex is the paralog of", "is the paralog of the", "the paralog of the budding", "paralog of the budding yeast", "of the budding yeast swi/snf", "the budding yeast swi/snf complex.", "budding yeast swi/snf complex. cbaf", "yeast swi/snf complex. cbaf is", "swi/snf complex. cbaf is smaller", "complex. cbaf is smaller and", "cbaf is smaller and more", "is smaller and more abundant", "smaller and more abundant than", "and more abundant than the", "more abundant than the related", "abundant than the related polybromo", "than the related polybromo associated", "the related polybromo associated baf", "polybromo associated baf pbaf", "baf pbaf complex.", "pbaf complex. shared between", "complex. shared between the two", "shared between the two complexes", "between the two complexes are", "the two complexes are proteins", "complexes are proteins or", "are proteins or members", "proteins or members of", "or members of protein families", "of protein families that", "protein families that make", "families that make up", "that make up the core", "make up the core of", "up the core of both", "the core of both complexes", "of both complexes including", "both complexes including smarcc", "complexes including smarcc and", "including smarcc and smarcd proteins", "and smarcd proteins the", "smarcd proteins the catalytic", "proteins the catalytic subunits", "catalytic subunits smarca4 brg1", "smarca4 brg1 or", "actb actl6a/b and bcl7a/b/c", "actl6a/b and bcl7a/b/c wang", "bcl7a/b/c wang cote", "wang cote et al", "cote et al 1996", "al 1996 wang", "1996 wang xue", "wang xue et al", "xue et al 1996", "al 1996 mashtalir", "1996 mashtalir et al", "mashtalir et al 2018", "al 2018 mashtalir", "2018 mashtalir et al", "mashtalir et al 2020", "al 2020 he", "2020 he et al", "he et al 2020", "al 2020 reviewed", "2020 reviewed in mittal", "reviewed in mittal and robert2", "mittal and robert2 2020", "robert2 2020 cenik", "2020 cenik and shilatifard", "cenik and shilatifard 2021", "shilatifard 2021 wang", "2021 wang and tang", "wang and tang 2023", "and tang 2023 .", "tang 2023 . distinguishing", "2023 . distinguishing components of", ". distinguishing components of the", "distinguishing components of the cbaf", "components of the cbaf complex", "of the cbaf complex include", "the cbaf complex include arid1a", "cbaf complex include arid1a or", "complex include arid1a or arid1b", "arid1a or arid1b and", "or arid1b and dpf1/2/3", "and dpf1/2/3 and ss18", "dpf1/2/3 and ss18 or", "ss18 or ss18l1 shared", "or ss18l1 shared with", "ss18l1 shared with ncbaf", "shared with ncbaf described", "with ncbaf described below", "described below reviewed", "below reviewed in", "reviewed in mittal and roberts", "mittal and roberts 2020", "roberts 2020 cenik", "shilatifard 2021 innis", "2021 innis and cabot", "innis and cabot 2020", "cabot 2020 wang", "2020 wang and tang", "and tang 2023 .
              mammalian", "tang 2023 .
              mammalian cbaf", "2023 .
              mammalian cbaf complexes are", ".
              mammalian cbaf complexes are required", "cbaf complexes are required for", "complexes are required for chromatin", "are required for chromatin remodelling", "required for chromatin remodelling and", "for chromatin remodelling and oppose", "chromatin remodelling and oppose polycomb", "remodelling and oppose polycomb repression", "oppose polycomb repression kadoch", "polycomb repression kadoch et", "repression kadoch et al", "kadoch et al 2017", "al 2017 stanton", "2017 stanton et al", "stanton et al 2017", "al 2017 wilson", "2017 wilson et al", "wilson et al 2010", "et al 2010 .", "al 2010 . unlike", "2010 . unlike in yeast", "unlike in yeast however", "yeast however mammalian", "however mammalian cbaf complexes", "mammalian cbaf complexes are able", "cbaf complexes are able to", "complexes are able to support", "are able to support both", "able to support both gene", "to support both gene activation", "support both gene activation and", "both gene activation and repression", "activation and repression boyer", "and repression boyer et", "repression boyer et al", "boyer et al 2005", "al 2005 ho", "2005 ho et al", "ho et al 2009", "et al 2009 ." ] }, { "record_id": "GLY_000594_1_2204", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9933946", "r hsa", "hsa 9933946", "r hsa 9933946" ] }, { "record_id": "GLY_000594_1_2204", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "formation of", "of the", "the embryonic", "embryonic stem", "stem cell", "cell baf", "formation of the", "of the embryonic", "the embryonic stem", "embryonic stem cell", "stem cell baf", "baf esbaf", "esbaf complex", "formation of the embryonic", "of the embryonic stem", "the embryonic stem cell", "embryonic stem cell baf", "cell baf esbaf", "formation of the embryonic stem", "of the embryonic stem cell", "the embryonic stem cell baf", "stem cell baf esbaf", "baf esbaf complex", "a distinct", "distinct baf", "baf complex", "complex has", "has been", "been identified", "identified in", "in mouse", "mouse and", "and human", "human embryonic", "stem cells", "jothi et", "et al", "ronan et", "zhang et", "reviewed in", "in kadoch", "kadoch and", "and crabtree", "cenik and", "and shilatifard", "innis and", "and cabot", "2020 .", ". esbaf", "esbaf is", "is characterized", "characterized by", "by the", "the presence", "presence of", "of smarca4/brg1", "smarca4/brg1 to", "to the", "the exclusion", "exclusion of", "of smarca2/brm", "smarca2/brm and", "and smarcd1/baf60a.", "smarcd1/baf60a. where", "where mouse", "mouse esbaf", "esbaf uses", "uses only", "only smarcc1", "human esbaf", "esbaf appears", "appears to", "to contain", "contain both", "both smarcc1", "and smarcc2", "wade et", "2015 .", "esbaf also", "also contains", "contains subunits", "subunits bcl11a/b", "kadoch et", "2021 .
              esbaf", ".
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              as", ".
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              as the", ".
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              this", "t cell activation.
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              this signaling pathway is", "signaling pathway is essential", "pathway is essential for", "is essential for modulating", "essential for modulating the", "for modulating the immune", "modulating the immune response", "immune response particularly", "response particularly in", "particularly in maintaining peripheral", "in maintaining peripheral tolerance", "maintaining peripheral tolerance and", "peripheral tolerance and preventing", "tolerance and preventing the", "and preventing the overactivation", "preventing the overactivation of", "the overactivation of t", "overactivation of t cells", "of t cells that", "t cells that can", "cells that can lead", "that can lead to", "can lead to autoimmune", "lead to autoimmune diseases.", "to autoimmune diseases. btla", "autoimmune diseases. btla is", "diseases. btla is expressed", "btla is expressed on", "is expressed on various", "expressed on various immune", "on various immune cells", "immune cells including", "cells including t", "t cells b", "cells b cells", "b cells and", "cells and dendritic", "dendritic cells and", "cells and it", "and it functions similarly", "it functions similarly to", "functions similarly to other", "similarly to other immune", "to other immune checkpoint", "other immune checkpoint molecules", "immune checkpoint molecules like", "checkpoint molecules like ctla", "molecules like ctla 4", "like ctla 4 and", "ctla 4 and pd", "4 and pd 1", "pd 1 but", "1 but it", "but it has unique", "it has unique structural", "has unique structural and", "unique structural and functional", "structural and functional properties.
              btla's", "and functional properties.
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              btla's interaction with", "properties.
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              this", "inhibiting t cell activation.
              this signaling", "t cell activation.
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              this signaling pathway is essential", "signaling pathway is essential for", "pathway is essential for modulating", "is essential for modulating the", "essential for modulating the immune", "for modulating the immune response", "the immune response particularly", "immune response particularly in", "response particularly in maintaining", "particularly in maintaining peripheral tolerance", "in maintaining peripheral tolerance and", "maintaining peripheral tolerance and preventing", "peripheral tolerance and preventing the", "tolerance and preventing the overactivation", "and preventing the overactivation of", "preventing the overactivation of t", "the overactivation of t cells", "overactivation of t cells that", "of t cells that can", "t cells that can lead", "cells that can lead to", "that can lead to autoimmune", "can lead to autoimmune diseases.", "lead to autoimmune diseases. btla", "to autoimmune diseases. btla is", "autoimmune diseases. btla is expressed", "diseases. btla is expressed on", "btla is expressed on various", "is expressed on various immune", "expressed on various immune cells", "various immune cells including", "immune cells including t", "cells including t cells", "including t cells b", "t cells b cells", "b cells and dendritic", "cells and dendritic cells", "and dendritic cells and", "dendritic cells and it", "cells and it functions", "and it functions similarly to", "it functions similarly to other", "functions similarly to other immune", "similarly to other immune checkpoint", "to other immune checkpoint molecules", "other immune checkpoint molecules like", "immune checkpoint molecules like ctla", "checkpoint molecules like ctla 4", "molecules like ctla 4 and", "like ctla 4 and pd", "ctla 4 and pd 1", "and pd 1 but", "pd 1 but it", "1 but it has", "but it has unique structural", "it has unique structural and", "has unique structural and functional", "unique structural and functional properties.
              btla's", "structural and functional properties.
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              btla's interaction with", "functional properties.
              btla's interaction with hvem", "properties.
              btla's interaction with hvem also", "interaction with hvem also influences", "with hvem also influences the", "hvem also influences the function", "also influences the function of", "influences the function of other", "the function of other immune", "function of other immune cells.", "of other immune cells. for", "other immune cells. for instance", "cells. for instance hvem", "for instance hvem is", "instance hvem is expressed", "hvem is expressed on many", "is expressed on many cell", "expressed on many cell types", "many cell types including", "cell types including t", "types including t cells", "b cells and myeloid", "cells and myeloid cells", "and myeloid cells and", "myeloid cells and its", "cells and its interaction", "and its interaction with btla", "its interaction with btla can", "interaction with btla can modulate", "with btla can modulate the", "btla can modulate the immune", "can modulate the immune response", "modulate the immune response in", "the immune response in a", "immune response in a context", "response in a context dependent", "in a context dependent manner.", "a context dependent manner. this", "context dependent manner. this complex", "dependent manner. this complex interplay", "manner. this complex interplay is", "this complex interplay is crucial", "complex interplay is crucial for", "interplay is crucial for fine", "is crucial for fine tuning", "crucial for fine tuning immune", "for fine tuning immune responses", "fine tuning immune responses and", "tuning immune responses and ensuring", "immune responses and ensuring that", "responses and ensuring that immune", "and ensuring that immune activation", "ensuring that immune activation is", "that immune activation is appropriately", "immune activation is appropriately regulated." ] }, { "record_id": "GLY_000594_1_2209", "filename": "human_protein_pathways_reactome", "fieldtype": "id", "phraselist": [ "gly_000594", "hsa", "9925561", "r hsa", "hsa 9925561", "r hsa 9925561" ] }, { "record_id": "GLY_000594_1_2209", "filename": "human_protein_pathways_reactome", "fieldtype": "text", "phraselist": [ "developmental lineage", "lineage of", "of pancreatic", "pancreatic acinar", "acinar cells", "developmental lineage of", "lineage of pancreatic", "of pancreatic acinar", "pancreatic acinar cells", "developmental lineage of pancreatic", "lineage of pancreatic acinar", "of pancreatic acinar cells", "developmental lineage of pancreatic acinar", "lineage of pancreatic acinar cells", "

              the exocrine", "exocrine pancreas", "which comprises", "comprises more", "more than", "than 95%", "95% of", "of the", "the pancreas", "pancreas mass", "consists of", "of lobules", "lobules formed", "formed by", "by tubuloacinar", "tubuloacinar glands", "glands that", "that are", "are built", "built by", "by two", "two cell", "cell types:", "types: acinar", "cells and", "and ductal", "ductal cells.", "cells. a", "a third", "centroacinar cells", "cells type", "type has", "has been", "been identified", "identified in", "in murine", "murine studies", "but their", "their existence", "existence and", "and functional", "functional role", "role is", "is under", "under debate.", "debate. acinar", "cells are", "are large", "large pyramidal", "pyramidal secretory", "secretory epithelial", "epithelial cells", "with apical", "apical basal", "basal polarization", "that surround", "surround the", "the lumen", "lumen of", "the acinus.", "acinus. acinar", "cells have", "have prominent", "prominent endoplasmic", "endoplasmic reticulum", "reticulum and", "and golgi", "golgi networks", "and their", "their cytoplasm", "cytoplasm contains", "contains a", "a large", "large number", "number of", "of secretory", "secretory zymogen", "zymogen granules", "filled with", "with various", "various digestive", "digestive enzymes", "are clustered", "clustered in", "in the", "the vicinity", "vicinity of", "the apical", "apical surface.", "surface. at", "at the", "the surface", "surface of", "are attached", "attached to", "to each", "each other", "other by", "by apical", "apical tight", "tight junctions", "while their", "their basal", "basal surfaces", "surfaces are", "are associated", "associated with", "with the", "the basal", "basal lamina.", "lamina. for", "for overview", "please refer", "refer to", "to liggitt", "liggitt and", "and dintzis", "241 250.", "250. for", "for review", "to tritschler", "tritschler et", "et al.", "al. 2017.

              pancreatic", "2017.

              pancreatic acinar", "cells originate", "originate from", "from definitive", "definitive endoderm", "endoderm cells", "cells that", "that form", "form during", "during gastrulation", "and then", "then undergo", "undergo patterning", "patterning along", "along anterior/posterior", "and median/lateral", "median/lateral axes", "among other", "other embryonal", "embryonal cell", "cell types", "cells of", "of dorsal", "dorsal and", "and ventral", "ventral foregut", "after transitioning", "transitioning through", "through an", "an intermediary", "intermediary duodeno", "duodeno pancreatic", "pancreatic endoderm", "endoderm cell", "cell state", "state for", "for dorsal", "dorsal foregut", "foregut endoderm", "endoderm and", "and possibly", "possibly a", "a hepato", "hepato pancreatic", "pancreatic or", "or pancreato", "pancreato biliary", "biliary intermediary", "intermediary state", "for ventral", "give rise", "rise to", "to multipotent", "multipotent pancreatic", "pancreatic progenitor", "progenitor cells", "form dorsal", "ventral pancreatic", "pancreatic buds", "yu et", "al. 2019", "reviewed in", "in jennings", "jennings et", "al. 2015", "2015 .", ". developing", "developing pancreas", "pancreas undergoes", "undergoes branching", "branching morphogenesis", "which results", "results in", "basal polarity", "polarity that", "that is", "is critical", "critical for", "for establishing", "establishing the", "the acinar", "acinar ductal", "ductal functional", "functional unit", "darrigrand et", "al. 2024", "2024 .", ". both", "both dorsal", "ventral mpcs", "mpcs located", "located at", "the tips", "tips of", "the developing", "branching pancreas", "start committing", "committing to", "to the", "acinar cell", "cell fate", "fate from", "from carnegie", "carnegie stage", "stage 19", "45 47", "47 days", "days post", "post conception", "of human", "human embryonic", "embryonic development", "development and", "and around", "around embryonic", "embryonic day", "day e12", "e12 during", "during mouse", "mouse development", "initially becoming", "becoming distinct", "distinct tip", "tip progenitors", "then pro", "pro acinar", "acinar and", "and acinar", "2015 .

              ", "

              the exocrine pancreas", "pancreas which", "which comprises more", "comprises more than", "more than 95%", "than 95% of", "95% of the", "of the pancreas", "the pancreas mass", "mass consists", "consists of lobules", "of lobules formed", "lobules formed by", "formed by tubuloacinar", "by tubuloacinar glands", "tubuloacinar glands that", "glands that are", "that are built", "are built by", "built by two", "by two cell", "two cell types:", "cell types: acinar", "types: acinar cells", "acinar cells and", "cells and ductal", "and ductal cells.", "ductal cells. a", "cells. a third", "third centroacinar", "centroacinar cells type", "cells type has", "type has been", "has been identified", "been identified in", "identified in murine", "in murine studies", "studies but", "but their existence", "their existence and", "existence and functional", "and functional role", "functional role is", "role is under", "is under debate.", "under debate. acinar", "debate. acinar cells", "acinar cells are", "cells are large", "are large pyramidal", "large pyramidal secretory", "pyramidal secretory epithelial", "secretory epithelial cells", "cells with", "with apical basal", "apical basal polarization", "polarization that", "that surround the", "surround the lumen", "the lumen of", "lumen of the", "of the acinus.", "the acinus. acinar", "acinus. acinar cells", "acinar cells have", "cells have prominent", "have prominent endoplasmic", "prominent endoplasmic reticulum", "endoplasmic reticulum and", "reticulum and golgi", "and golgi networks", "networks and", "and their cytoplasm", "their cytoplasm contains", "cytoplasm contains a", "contains a large", "a large number", "large number of", "number of secretory", "of secretory zymogen", "secretory zymogen granules", "granules filled", "filled with various", "with various digestive", "various digestive enzymes", "enzymes that", "that are clustered", "are clustered in", "clustered in the", "in the vicinity", "the vicinity of", "vicinity of the", "of the apical", "the apical surface.", "apical surface. at", "surface. at the", "at the surface", "the surface of", "surface of the", "of the lumen", "lumen acinar", "cells are attached", "are attached to", "attached to each", "to each other", "each other by", "other by apical", "by apical tight", "apical tight junctions", "junctions while", "while their basal", "their basal surfaces", "basal surfaces are", "surfaces are associated", "are associated with", "associated with the", "with the basal", "the basal lamina.", "basal lamina. for", "lamina. for overview", "overview please", "please refer to", "refer to liggitt", "to liggitt and", "liggitt and dintzis", "dintzis \u201cpancreas\u201d", "\u201cpancreas\u201d 241", "241 250. for", "250. for review", "review please", "refer to tritschler", "to tritschler et", "tritschler et al.", "et al. 2017.

              pancreatic", "al. 2017.

              pancreatic acinar", "2017.

              pancreatic acinar cells", "acinar cells originate", "cells originate from", "originate from definitive", "from definitive endoderm", "definitive endoderm cells", "endoderm cells that", "cells that form", "that form during", "form during gastrulation", "gastrulation and", "and then undergo", "then undergo patterning", "undergo patterning along", "patterning along anterior/posterior", "anterior/posterior dorsal/ventral", "dorsal/ventral and", "and median/lateral axes", "axes producing", "producing among", "among other embryonal", "other embryonal cell", "embryonal cell types", "types endoderm", "endoderm cells of", "cells of dorsal", "of dorsal and", "dorsal and ventral", "and ventral foregut", "foregut which", "which after", "after transitioning through", "transitioning through an", "through an intermediary", "an intermediary duodeno", "intermediary duodeno pancreatic", "duodeno pancreatic endoderm", "pancreatic endoderm cell", "endoderm cell state", "cell state for", "state for dorsal", "for dorsal foregut", "dorsal foregut endoderm", "foregut endoderm and", "endoderm and possibly", "and possibly a", "possibly a hepato", "a hepato pancreatic", "hepato pancreatic or", "pancreatic or pancreato", "or pancreato biliary", "pancreato biliary intermediary", "biliary intermediary state", "intermediary state for", "state for ventral", "for ventral foregut", "ventral foregut endoderm", "endoderm give", "give rise to", "rise to multipotent", "to multipotent pancreatic", "multipotent pancreatic progenitor", "pancreatic progenitor cells", "cells mpcs", "mpcs that", "that form dorsal", "form dorsal and", "and ventral pancreatic", "ventral pancreatic buds", "buds yu", "yu et al.", "et al. 2019", "2019 reviewed", "reviewed in jennings", "in jennings et", "jennings et al.", "et al. 2015", "al. 2015 .", "2015 . developing", ". developing pancreas", "developing pancreas undergoes", "pancreas undergoes branching", "undergoes branching morphogenesis", "morphogenesis which", "which results in", "results in the", "in the apical", "the apical basal", "apical basal polarity", "basal polarity that", "polarity that is", "that is critical", "is critical for", "critical for establishing", "for establishing the", "establishing the acinar", "the acinar ductal", "acinar ductal functional", "ductal functional unit", "unit darrigrand", "darrigrand et al.", "et al. 2024", "al. 2024 .", "2024 . both", ". both dorsal", "both dorsal and", "and ventral mpcs", "ventral mpcs located", "mpcs located at", "located at the", "at the tips", "the tips of", "tips of the", "of the developing", "developing branching", "pancreas start", "start committing to", "committing to the", "to the acinar", "the acinar cell", "acinar cell fate", "cell fate from", "fate from carnegie", "from carnegie stage", "carnegie stage 19", "19 45", "45 47 days", "47 days post", "days post conception", "conception of", "of human embryonic", "human embryonic development", "embryonic development and", "development and around", "and around embryonic", "around embryonic day", "embryonic day e12", "day e12 during", "e12 during mouse", "during mouse development", "development initially", "initially becoming distinct", "becoming distinct tip", "distinct tip progenitors", "progenitors and", "and then pro", "then pro acinar", "pro acinar and", "acinar and acinar", "and acinar cells", "cells yu", "al. 2015 .

              ", "exocrine pancreas which", "pancreas which comprises", "which comprises more than", "comprises more than 95%", "more than 95% of", "than 95% of the", "95% of the pancreas", "of the pancreas mass", "pancreas mass consists", "mass consists of", "consists of lobules formed", "of lobules formed by", "lobules formed by tubuloacinar", "formed by tubuloacinar glands", "by tubuloacinar glands that", "tubuloacinar glands that are", "glands that are built", "that are built by", "are built by two", "built by two cell", "by two cell types:", "two cell types: acinar", "cell types: acinar cells", "types: acinar cells and", "acinar cells and ductal", "cells and ductal cells.", "and ductal cells. a", "ductal cells. a third", "a third centroacinar", "third centroacinar cells", "centroacinar cells type has", "cells type has been", "type has been identified", "has been identified in", "been identified in murine", "identified in murine studies", "murine studies but", "studies but their", "but their existence and", "their existence and functional", "existence and functional role", "and functional role is", "functional role is under", "role is under debate.", "is under debate. acinar", "under debate. acinar cells", "debate. acinar cells are", "acinar cells are large", "cells are large pyramidal", "are large pyramidal secretory", "large pyramidal secretory epithelial", "pyramidal secretory epithelial cells", "epithelial cells with", "cells with apical", "with apical basal polarization", "basal polarization that", "polarization that surround", "that surround the lumen", "surround the lumen of", "the lumen of the", "lumen of the acinus.", "of the acinus. acinar", "the acinus. acinar cells", "acinus. acinar cells have", "acinar cells have prominent", "cells have prominent endoplasmic", "have prominent endoplasmic reticulum", "prominent endoplasmic reticulum and", "endoplasmic reticulum and golgi", "reticulum and golgi networks", "golgi networks and", "networks and their", "and their cytoplasm contains", "their cytoplasm contains a", "cytoplasm contains a large", "contains a large number", "a large number of", "large number of secretory", "number of secretory zymogen", "of secretory zymogen granules", "zymogen granules filled", "granules filled with", "filled with various digestive", "with various digestive enzymes", "digestive enzymes that", "enzymes that are", "that are clustered in", "are clustered in the", "clustered in the vicinity", "in the vicinity of", "the vicinity of the", "vicinity of the apical", "of the apical surface.", "the apical surface. at", "apical surface. at the", "surface. at the surface", "at the surface of", "the surface of the", "surface of the lumen", "the lumen acinar", "lumen acinar cells", "acinar cells are attached", "cells are attached to", "are attached to each", "attached to each other", "to each other by", "each other by apical", "other by apical tight", "by apical tight junctions", "tight junctions while", "junctions while their", "while their basal surfaces", "their basal surfaces are", "basal surfaces are associated", "surfaces are associated with", "are associated with the", "associated with the basal", "with the basal lamina.", "the basal lamina. for", "basal lamina. for overview", "for overview please", "overview please refer", "please refer to liggitt", "refer to liggitt and", "to liggitt and dintzis", "and dintzis \u201cpancreas\u201d", "\u201cpancreas\u201d 241 250.", "241 250. for review", "for review please", "review please refer", "please refer to tritschler", "refer to tritschler et", "to tritschler et al.", "tritschler et al. 2017.

              pancreatic", "et al. 2017.

              pancreatic acinar", "al. 2017.

              pancreatic acinar cells", "2017.

              pancreatic acinar cells originate", "acinar cells originate from", "cells originate from definitive", "originate from definitive endoderm", "from definitive endoderm cells", "definitive endoderm cells that", "endoderm cells that form", "cells that form during", "that form during gastrulation", "during gastrulation and", "gastrulation and then", "and then undergo patterning", "then undergo patterning along", "undergo patterning along anterior/posterior", "along anterior/posterior dorsal/ventral", "dorsal/ventral and median/lateral", "median/lateral axes producing", "producing among other", "among other embryonal cell", "other embryonal cell types", "cell types endoderm", "types endoderm cells", "endoderm cells of dorsal", "cells of dorsal and", "of dorsal and ventral", "dorsal and ventral foregut", "ventral foregut which", "which after transitioning", "after transitioning through an", "transitioning through an intermediary", "through an intermediary duodeno", "an intermediary duodeno pancreatic", "intermediary duodeno pancreatic endoderm", "duodeno pancreatic endoderm cell", "pancreatic endoderm cell state", "endoderm cell state for", "cell state for dorsal", "state for dorsal foregut", "for dorsal foregut endoderm", "dorsal foregut endoderm and", "foregut endoderm and possibly", "endoderm and possibly a", "and possibly a hepato", "possibly a hepato pancreatic", "a hepato pancreatic or", "hepato pancreatic or pancreato", "pancreatic or pancreato biliary", "or pancreato biliary intermediary", "pancreato biliary intermediary state", "biliary intermediary state for", "intermediary state for ventral", "state for ventral foregut", "for ventral foregut endoderm", "foregut endoderm give", "endoderm give rise", "give rise to multipotent", "rise to multipotent pancreatic", "to multipotent pancreatic progenitor", "multipotent pancreatic progenitor cells", "progenitor cells mpcs", "mpcs that form", "that form dorsal and", "form dorsal and ventral", "dorsal and ventral pancreatic", "and ventral pancreatic buds", "pancreatic buds yu", "buds yu et", "yu et al. 2019", "al. 2019 reviewed", "2019 reviewed in", "reviewed in jennings et", "in jennings et al.", "jennings et al. 2015", "et al. 2015 .", "al. 2015 . developing", "2015 . developing pancreas", ". developing pancreas undergoes", "developing pancreas undergoes branching", "pancreas undergoes branching morphogenesis", "branching morphogenesis which", "morphogenesis which results", "which results in the", "results in the apical", "in the apical basal", "the apical basal polarity", "apical basal polarity that", "basal polarity that is", "polarity that is critical", "that is critical for", "is critical for establishing", "critical for establishing the", "for establishing the acinar", "establishing the acinar ductal", "the acinar ductal functional", "acinar ductal functional unit", "functional unit darrigrand", "unit darrigrand et", "darrigrand et al. 2024", "et al. 2024 .", "al. 2024 . both", "2024 . both dorsal", ". both dorsal and", "both dorsal and ventral", "dorsal and ventral mpcs", "and ventral mpcs located", "ventral mpcs located at", "mpcs located at the", "located at the tips", "at the tips of", "the tips of the", "tips of the developing", "the developing branching", "developing branching pancreas", "branching pancreas start", "pancreas start committing", "start committing to the", "committing to the acinar", "to the acinar cell", "the acinar cell fate", "acinar cell fate from", "cell fate from carnegie", "fate from carnegie stage", "from carnegie stage 19", "stage 19 45", "19 45 47", "45 47 days post", "47 days post conception", "post conception of", "conception of human", "of human embryonic development", "human embryonic development and", "embryonic development and around", "development and around embryonic", "and around embryonic day", "around embryonic day e12", "embryonic day e12 during", "day e12 during mouse", "e12 during mouse development", "mouse development initially", "development initially becoming", "initially becoming distinct tip", "becoming distinct tip progenitors", "tip progenitors and", "progenitors and then", "and then pro acinar", "then pro acinar and", "pro acinar and acinar", "acinar and acinar cells", "acinar cells yu", "cells yu et", "et al. 2015 .

              ", "

              the exocrine pancreas which", "exocrine pancreas which comprises", "pancreas which comprises more", "which comprises more than 95%", "comprises more than 95% of", "more than 95% of the", "than 95% of the pancreas", "95% of the pancreas mass", "the pancreas mass consists", "pancreas mass consists of", "mass consists of lobules", "consists of lobules formed by", "of lobules formed by tubuloacinar", "lobules formed by tubuloacinar glands", "formed by tubuloacinar glands that", "by tubuloacinar glands that are", "tubuloacinar glands that are built", "glands that are built by", "that are built by two", "are built by two cell", "built by two cell types:", "by two cell types: acinar", "two cell types: acinar cells", "cell types: acinar cells and", "types: acinar cells and ductal", "acinar cells and ductal cells.", "cells and ductal cells. a", "and ductal cells. a third", "cells. a third centroacinar", "a third centroacinar cells", "third centroacinar cells type", "centroacinar cells type has been", "cells type has been identified", "type has been identified in", "has been identified in murine", "been identified in murine studies", "in murine studies but", "murine studies but their", "studies but their existence", "but their existence and functional", "their existence and functional role", "existence and functional role is", "and functional role is under", "functional role is under debate.", "role is under debate. acinar", "is under debate. acinar cells", "under debate. acinar cells are", "debate. acinar cells are large", "acinar cells are large pyramidal", "cells are large pyramidal secretory", "are large pyramidal secretory epithelial", "large pyramidal secretory epithelial cells", "secretory epithelial cells with", "epithelial cells with apical", "cells with apical basal", "apical basal polarization that", "basal polarization that surround", "polarization that surround the", "that surround the lumen of", "surround the lumen of the", "the lumen of the acinus.", "lumen of the acinus. acinar", "of the acinus. acinar cells", "the acinus. acinar cells have", "acinus. acinar cells have prominent", "acinar cells have prominent endoplasmic", "cells have prominent endoplasmic reticulum", "have prominent endoplasmic reticulum and", "prominent endoplasmic reticulum and golgi", "endoplasmic reticulum and golgi networks", "and golgi networks and", "golgi networks and their", "networks and their cytoplasm", "and their cytoplasm contains a", "their cytoplasm contains a large", "cytoplasm contains a large number", "contains a large number of", "a large number of secretory", "large number of secretory zymogen", "number of secretory zymogen granules", "secretory zymogen granules filled", "zymogen granules filled with", "granules filled with various", "filled with various digestive enzymes", "various digestive enzymes that", "digestive enzymes that are", "enzymes that are clustered", "that are clustered in the", "are clustered in the vicinity", "clustered in the vicinity of", "in the vicinity of the", "the vicinity of the apical", "vicinity of the apical surface.", "of the apical surface. at", "the apical surface. at the", "apical surface. at the surface", "surface. at the surface of", "at the surface of the", "the surface of the lumen", "of the lumen acinar", "the lumen acinar cells", "lumen acinar cells are", "acinar cells are attached to", "cells are attached to each", "are attached to each other", "attached to each other by", "to each other by apical", "each other by apical tight", "other by apical tight junctions", "apical tight junctions while", "tight junctions while their", "junctions while their basal", "while their basal surfaces are", "their basal surfaces are associated", "basal surfaces are associated with", "surfaces are associated with the", "are associated with the basal", "associated with the basal lamina.", "with the basal lamina. for", "the basal lamina. for overview", "lamina. for overview please", "for overview please refer", "overview please refer to", "please refer to liggitt and", "refer to liggitt and dintzis", "liggitt and dintzis \u201cpancreas\u201d", "dintzis \u201cpancreas\u201d 241", "\u201cpancreas\u201d 241 250. for", "250. for review please", "for review please refer", "review please refer to", "please refer to tritschler et", "refer to tritschler et al.", "to tritschler et al. 2017.

              pancreatic", "tritschler et al. 2017.

              pancreatic acinar", "et al. 2017.

              pancreatic acinar cells", "al. 2017.

              pancreatic acinar cells originate", "2017.

              pancreatic acinar cells originate from", "acinar cells originate from definitive", "cells originate from definitive endoderm", "originate from definitive endoderm cells", "from definitive endoderm cells that", "definitive endoderm cells that form", "endoderm cells that form during", "cells that form during gastrulation", "form during gastrulation and", "during gastrulation and then", "gastrulation and then undergo", "and then undergo patterning along", "then undergo patterning along anterior/posterior", "patterning along anterior/posterior dorsal/ventral", "anterior/posterior dorsal/ventral and", "dorsal/ventral and median/lateral axes", "and median/lateral axes producing", "axes producing among", "producing among other embryonal", "among other embryonal cell types", "embryonal cell types endoderm", "cell types endoderm cells", "types endoderm cells of", "endoderm cells of dorsal and", "cells of dorsal and ventral", "of dorsal and ventral foregut", "and ventral foregut which", "foregut which after", "which after transitioning through", "after transitioning through an intermediary", "transitioning through an intermediary duodeno", "through an intermediary duodeno pancreatic", "an intermediary duodeno pancreatic endoderm", "intermediary duodeno pancreatic endoderm cell", "duodeno pancreatic endoderm cell state", "pancreatic endoderm cell state for", "endoderm cell state for dorsal", "cell state for dorsal foregut", "state for dorsal foregut endoderm", "for dorsal foregut endoderm and", "dorsal foregut endoderm and possibly", "foregut endoderm and possibly a", "endoderm and possibly a hepato", "and possibly a hepato pancreatic", "possibly a hepato pancreatic or", "a hepato pancreatic or pancreato", "hepato pancreatic or pancreato biliary", "pancreatic or pancreato biliary intermediary", "or pancreato biliary intermediary state", "pancreato biliary intermediary state for", "biliary intermediary state for ventral", "intermediary state for ventral foregut", "state for ventral foregut endoderm", "ventral foregut endoderm give", "foregut endoderm give rise", "endoderm give rise to", "give rise to multipotent pancreatic", "rise to multipotent pancreatic progenitor", "to multipotent pancreatic progenitor cells", "pancreatic progenitor cells mpcs", "cells mpcs that", "mpcs that form dorsal", "that form dorsal and ventral", "form dorsal and ventral pancreatic", "dorsal and ventral pancreatic buds", "ventral pancreatic buds yu", "pancreatic buds yu et", "buds yu et al.", "et al. 2019 reviewed", "al. 2019 reviewed in", "2019 reviewed in jennings", "reviewed in jennings et al.", "in jennings et al. 2015", "jennings et al. 2015 .", "et al. 2015 . developing", "al. 2015 . developing pancreas", "2015 . developing pancreas undergoes", ". developing pancreas undergoes branching", "developing pancreas undergoes branching morphogenesis", "undergoes branching morphogenesis which", "branching morphogenesis which results", "morphogenesis which results in", "which results in the apical", "results in the apical basal", "in the apical basal polarity", "the apical basal polarity that", "apical basal polarity that is", "basal polarity that is critical", "polarity that is critical for", "that is critical for establishing", "is critical for establishing the", "critical for establishing the acinar", "for establishing the acinar ductal", "establishing the acinar ductal functional", "the acinar ductal functional unit", "ductal functional unit darrigrand", "functional unit darrigrand et", "unit darrigrand et al.", "darrigrand et al. 2024 .", "et al. 2024 . both", "al. 2024 . both dorsal", "2024 . both dorsal and", ". both dorsal and ventral", "both dorsal and ventral mpcs", "dorsal and ventral mpcs located", "and ventral mpcs located at", "ventral mpcs located at the", "mpcs located at the tips", "located at the tips of", "at the tips of the", "the tips of the developing", "of the developing branching", "the developing branching pancreas", "branching pancreas start committing", "pancreas start committing to", "start committing to the acinar", "committing to the acinar cell", "to the acinar cell fate", "the acinar cell fate from", "acinar cell fate from carnegie", "cell fate from carnegie stage", "fate from carnegie stage 19", "carnegie stage 19 45", "stage 19 45 47", "19 45 47 days", "45 47 days post conception", "days post conception of", "post conception of human", "conception of human embryonic", "of human embryonic development and", "human embryonic development and around", "embryonic development and around embryonic", "development and around embryonic day", "and around embryonic day e12", "around embryonic day e12 during", "embryonic day e12 during mouse", "day e12 during mouse development", "during mouse development initially", "mouse development initially becoming", "development initially becoming distinct", "initially becoming distinct tip progenitors", "distinct tip progenitors and", "tip progenitors and then", "progenitors and then pro", "and then pro acinar and", "then pro acinar and acinar", "pro acinar and acinar cells", "and acinar cells yu", "acinar cells yu et", "cells yu et al.", "jennings et al. 2015 .

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              rna", "and maquat 2024 .
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              the", "et al. 2016 .
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